ActivityReport IMM2004

IMM – Report | 1
IMM – Report | 2
INDEX
IMM- Past, Present and Future____________________________________ 3
IMM- Structure_________________________________________________ 4
IMM- Science & Society__________________________________________ 5
IMM- Cell & Dev. Biology Programme______________________________ 7
IMM- Immunology & Inf. Diseases Programme______________________ 33
IMM- Neurosciences Programme___________________________________ 53
IMM- Oncology Programme_______________________________________ 87
IMM- Indicators ________________________________________________ 110
IMM- Detailed R&D Activities_____________________________________ 111

IMM – Past, Present and Future 3
IMM – Past, Present and Future

Located on the campus of the University of Lisbon School of Medicine, The Institute of
Molecular Medicine (IMM) is an Associate Laboratory of the National Ministry of
Science and Higher Education. IMM is mainly supported by national public funds and
European Union funds (POCTI and FEDER). The research expenditure includes
additional funds obtained from peer reviewed grants (Fundação da Ciência e
Tecnologia, European Commission, Charities) and industrial partnerships.
Created in December 2001, IMM results from the association of 5 former research units
from the University of Lisbon School of Medicine: the Biology and Molecular
Pathology Centre (CEBIP), the Lisbon Neurosciences Centre (CNL), the
Microcirculation and Vascular Pathobiology Centre (CMBV), the Gastroenterology
Centre (CG) and the Nutrition and Metabolism Centre (CNB). In 2003, the Molecular
Pathobiology Research Centre (CIPM) of the Portuguese Institute of Oncology
Francisco Gentil (IPOFG) became an additional associate of IMM.
The Institute is a Private, Non-profit Association, whose associate members are the
University of Lisbon, the University of Lisbon School of Medicine, the Santa Maria
Hospital, the Portuguese Institute of Oncology Francisco Gentil, the University of
Lisbon Foundation, the Association for Research and Development of the University of
Lisbon Medical School, and the Oriente Foundation.
Research and development in the Biomedical Sciences plays a central role in generating
knowledge and in the application of this knowledge to improving the quality of life. The
mission of the Institute is to foster basic, clinical and translational biomedical Research
with the aim of contributing to a better understanding of disease mechanisms,
developing novel predictive tests, improving diagnostics tools and developing new
therapeutic approaches.
Presently, the R&D activities that take place at IMM are focused on 4 major
Programmes: Cell and Developmental Biology, Immunology and Infectious Diseases,
Neurosciences and Oncology.
IMM – Structure 4
IMM - Structure
Board of Directors
João Lobo Antunes, MD, PhD – President

Maria Carmo-Fonseca, MD, PhD – Executive Director
Miguel Carneiro de Moura, MD, PhD – Vice-President
Management Committee
José Ferro, MD, PhD

Alexandre Ribeiro, MD, PhD
Ermelinda Camilo, MD, PhD
Luís Silva Carvalho, MD, PhD
Rui Victorino, MD, PhD
Leonor Parreira, MD, PhD
António Parreira, MD, PhD
Sérgio Dias, MD, PhD
Management Unit
Margarida Pinto Gago, Administrator & Finance Officer

Maria José Proença, Laboratory Management & Safety Officer
Patrícia Cunha, Secretariat
Isabel Roque, Accounting
Ricardo Saraiva, Information Technologies
Francisca Menezes Ferreira, Science Commnunication & Marketing
IMM – Science & Society 5
IMM – Science & Society
1. IMM’s Website
In April 2003, IMM’s Science Communication and Marketing Unit coordinated by Maria
Francisca Wright de Menezes Ferreira began to develop the concept and basic content for the
construction of a fully interactive and experimental website on biomedical research and
technology. The aim of the project has since been to explore the potential of the Internet for
communicating science to a wide audience and engage all sectors of society in the creation of a
common ground for the debate of related social, ethical and S&T Policy issues. Moreover, it is
our objective to launch an R&D project into public perceptions and attitudes to science and
technology in Portugal. IMM’s newly restructured website was launched on 1 April 2004..
2. EDAB International Brain Awareness Week (15-21 March 2004)
Semana Internacional do Cérebro 2004 – Radio Interview to TSF given by Professor J. Alexandre
Ribeiro was organised by Maria Francisca Wright de Menezes Ferreira. Lisboa, 15 March 2004.
Semana Internacional do Cérebro 2004 – Press Conference “Dormir Bem, Viver Melhor”,
delivered by Professor Teresa Paiva, was organised by Maria Francisca Wright de Menezes
Ferreira. Aula Magna da Faculdade de Medicina de Lisboa, 16 March 2004.
Semana Internacional do Cérebro 2004 – Interview given by Professor Teresa Paiva to the
newspaper “PÚBLICO” was organised by Maria Francisca Wright de Menezes Ferreira. Article
entitled “Portugueses dormem cada vez menos”, by Joana Filipe, was published on 17 March
2004.
Semana Internacional do Cérebro 2004 – Debate with secondary school students at Escola
Secundária de Cascais on “A acção das drogas no cérebro – Neurofarmacologia, Psicologia e
Psiquiatria” mediated by Professors J. Alexandre Ribeiro and Ana M. Sebastião, and “A
importância do sono para a Qualidade de Vida”, mediated by Professor Teresa Paiva organised by
Maria Francisca Wright de Menezes Ferreira. Escola Secundária de Cascais, 17 March 2004.
3. Workshops for Secondary School Teachers
The first workshop “Inspirar Ciência” on Developmental Biology was co-organised by Maria
Francisca Wright de Menezes Ferreira in collaboration with Instituto Gulbenkian de Ciência, the
European Learning Laboratory for the Life Sciences (ELLS) and the European Molecular
Biology Organisation (EMBO). Instituto Gulbenkian de Ciência, Oeiras, 13-15 April 2004.
4. Invited Lectures
Maria Francisca Wright de Menezes Ferreira: “Educational Resources on the Internet”. I

Workshop “Inspirar Ciência” sobre Biologia do Desenvolvimento, Instituto Gulbenkian de
Ciência, Oeiras, 15 April 2004.
IMM – Science & Society 6
5. Press Releases
Maria Francisca Wright de Menezes Ferreira: “Prémio Pfizer de Investigação 2003 Atribuído a
Estudo de Células Estaminais do Sangue”. Comunicado de Imprensa conjunto do Instituto de
Medicina Molecular e do Instituto Gulbenkian de Ciência, 5 February 2004.
Maria Francisca Wright de Menezes Ferreira: “Semana Internacional do Cérebro 2004 -

Conferência de Imprensa "Dormir Bem, Viver Melhor", 12 March 2004.
Maria Francisca Wright de Menezes Ferreira: “Semana Internacional do Cérebro 2004 - Debate
na Escola Secundária de Cascais Sobre a Acção das Drogas no Cérebro e a Importância do Sono
para a Qualidade de Vida”, 12 March 2004.
Maria Francisca Wright de Menezes Ferreira: “Neurocientistas do IMM Contribuem para o

Desenvolvimento de Novas Estratégias Terapêuticas para as Doenças Neurodegenerativas”.
19 May 2004.
Maria Francisca Wright de Menezes Ferreira: “Gene Delta 4 Desempenha Papel Primordial na
Formação do Sistema Vascular Humano”, 27 October 2004.
Maria Francisca Wright de Menezes Ferreira: “WSTF - Uma Proteína Envolvida na Gravação da
Memória Celular”, 30 November 2004.
IMM – Cell & Dev. Biology Programme | 7
Cell and Developmental Biology Programme
Cell Biology Unit
Description and Objectives
The main objective of the Cell Biology Unit is to investigate the regulation of gene expression
within the sophisticated environment that is the nucleus of a living cell. Presently, the
development of genetic technologies with therapeutic application is still limited by the lack of
basic knowledge concerning the ways in which genes function. The information encoded in genes
must be translated into proteins which represent the building blocks of the different tissues in the
human body. How gene information turns into protein information can be modulated by a cellular
process termed splicing. We are particularly interested in understanding how splicing is regulated
and how errors in this process lead to human disease.
Coordinator/Principal Investigator
Maria Carmo-Fonseca, MD, PhD – Full Professor, FML
Research Team
José Francisco David Ferreira, MD, PhD - Professor Emeritus, FML

Teresa Carvalho, MD, PhD - Auxiliary Professor, FML
Margarida Gama-Carvalho, PhD - Auxiliary Professor, FML
Joana Desterro, PhD - Auxiliary Professor, FML
Célia Carvalho – Assistant, FML
Noélia Custódio – Assistant, FML
Sandra Caldeira, PhD - Post-Doc Fellowship, FCT
Anita Gomes, PhD - Post-Doc Fellowship, FCT
Maria Vivo, PhD - Post-Doc Fellowship, FCT
Natalia Kozlova, PhD - Post-Doc Fellowship, FCT
Sandra Martins, PhD - Post-Doc Fellowship, FCT
Eoin Fleming, PhD - Post-Doc Fellowship, FCT
João Paulo Tavanez - PhD Fellowship, FCT
Tiago Carneiro - PhD Fellowship, FCT
Patrícia Calado - PhD Fellowship, FCT
José Rino - PhD Fellowship, FCT
José Braga - PhD Fellowship, FCT
Nuno Morais - PhD Fellowship, FCT
Inês Mollet - PhD Fellow
Maria do Carmo Silva – Technician, FML
Research Areas
Cell and Molecular Biology

Biogenesis of messenger RNA
RNA splicing
Diseases of RNA metabolism
Recent Most Relevant Publications
Custódio, N., Carmo-Fonseca, M., Geraghty, F., Pereira, H.S., Grosveld, F., and Antoniou, M.
(1999) Inefficient processing impairs release of RNA from the site of transcription. EMBO J.
18:2855-2866. (Times cited: 77) (Journal IF: 10.456)
Carmo-Fonseca, M., Mendes-Soares, L., and Campos, I. (2000) To be or not to be in the

nucleolus. Nature Cell Biology 2:E107-E112. (Times cited: 55) (Journal IF: 11.939)
Calado, A., Tomé, F.M.S., Brais, B., Rouleau, G.A., Kühn, U., Wahle, E., and Carmo-Fonseca,
M. (2000) Nuclear inclusions in oculopharyngeal muscular dystrophy consist of poly(A) binding
protein 2 aggregates which sequester poly(A) RNA. Human Molecular Genetics 9:2321-2328.
(Times cited: 40) (Journal IF: 9.048)
Carmo-Fonseca, M. (2002) The contribution of nuclear compartmentalization to gene regulation.

Cell 108:1-20. (Times cited: 65) (Journal IF: 27.254)
Calapez, A., Pereira, H.M., Calado, A., Braga, J., Rino, J., Carvalho, C., Tavanez, J.P., Wahle, E.,
Rosa, A.C., and Carmo-Fonseca, M. (2002) The intranuclear mobility of messenger RNA binding
proteins is ATP-dependent and temperature-sensitive. J. Cell Biol. 159:795-805
Ongoing Research Projects
2001/05 Genetic Diseases and RNA Processing. Fundação para a Ciência e Tecnologia
(POCTI/MGI/ 36547/00)
2001/05 RNOMICS: An integrated analysis of links between pathways of RNA

metabolism in the post-genomic era (QLRT-2000-01554)
2002/05 TRI-EX: Oculopharyngeal muscular dystrophy – a paradigm to investigate new

pharmaco-therapeutic approaches to trinucleotide expansion diseases and
muscular dystrophies (QLRT-2001-01673)
2004/09 MOLECULAR IMAGING: Integrated technologies for in vivo molecular

imaging (FP6-2002-CT-503259)
2004/06 Profiling alternative splicing in muscular dystrophies (MDA3662)

The aim of the research that is being conducted in our Laboratory is, on one hand, to decipher the
mechanisms involved in biogenesis of messenger RNA (mRNA) and, on the other, to contribute
to a better understanding of the pathogenesis of diseases caused by genetic errors that affect this
process.
Biogenesis of messenger RNA (mRNA) involves transcription of precursor molecules (pre-

mRNA), maturation of these precursors through a series of processing events and export of the
mature mRNA to the cytoplasm for translation. Errors in pre-mRNA processing represent a
primary cause of several human diseases. Current advances in understanding mRNA biogenesis
are leading to the development of novel therapeutic strategies directed toward correcting or
circumventing these abnormalities.
In our laboratory, we have established model systems to visualize the assembly of RNP
complexes in the nucleus of mammalian cells producing abundant pre-mRNA transcripts. One
such model consists of HeLa cells infected with adenovirus because this virus recruits the host
transcription and processing machinery to the sites of viral pre-mRNA synthesis. Another
consists of murine erythroleukemia (MEL) cells stably transfected with the human β-globin gene
under the control of the locus control region (LCR). The human β-globin gene, which integrates
in the host cell genome as a tandem array, expresses at physiological levels upon induction of
MEL cells to undergo terminal erythroid differentiation. Using these models, we have shown that
the exon junction complex proteins (a specific set of proteins that assemble on mRNA as a
consequence of splicing) bind co-transcriptionally to mRNPs and that efficient pre-mRNA
processing is required for assembly of the EJC complex onto nascent transcripts in vivo.
The splicing reaction involves the formation of a highly intricate assembly of the components of
the spliceosome. Using confocal microscopy, photobleaching and FRET techniques, we are
studying the dynamics of spliceosome assembly in human cells expressing splicing factors tagged
with fluorescent protein fusions.
Current models for the regulation of alternative splicing decisions involve combinatorial modes
of control in which particular combinations and concentrations of positive and negatively acting
factors determine the outcome of subsets of alternative splicing decisions. However, few genuine
validated cellular targets and splicing regulators are known. Moreover, the recent discovery of the
profound influence of transcription and other RNA processing events on splicing highlights the
importance of examining the role of splicing regulators on the alternative splicing of endogenous
genes. In our laboratory we set out to characterize endogenous substrates for specific splicing
proteins. Using RNA interference, we have shown that the general splicing factor U2AF35
regulates alternative splicing of pre-mRNAs that encode proteins required for cell cycle
progression.
It was recently discovered that the mutation responsible for Myotonic Dystrophy (DM) interferes
with the regulation of splicing, thereby altering the structure and function of specific muscle
proteins. We are interested in identifying additional proteins that may be malfunctioning in
dystrophic muscles due to errors in splicing regulation. To achieve this goal, we have been
establishing a database of muscle specific alternative splice events that allows the design of
oligonucleotides to be included in microarrays. In DM patients, abnormal pre-mRNA splicing is
caused by overexpression of the splicing regulator CUGPB and in Becker muscular dystrophy,
changes in the expression of CUGPB have also been reported. We have therefore cloned
CUGBP1 in a vector containing a desmin promoter and will stably overexpress this construct in
primary human skeletal muscle cells. This will constitute a novel human cellular model to study
splicing de-regulation in muscular dystrophies. In parallel, we have initiated an analysis of
splicing factor expression throughout muscle differentiation using the mouse C2 cell line as a
model.
Most eukaryotic messenger RNA (mRNA) molecules have a long tract of adenosine nucleotides
at the 3’ end, and this poly(A) tail seems to play a role in every step of the life of the mRNA.
Poly(A) addition is carried out by a poly(A) polymerase enzyme that on its own is nearly
inactive. In order to be active in polyadenylation, PAP depends on cleavage and polyadenylation
specificity factor (CPSF) and the nuclear poly(A) binding protein, PABPN1. In humans, an
expansion of a trinucleotide repeat in the PABPN1 gene causes oculopharyngeal muscular
dystrophy or OPMD. The OPMD expansion is translated into a polyalanine tract in PABPN1 and
because intranuclear inclusions containing this protein represent a pathological hallmark of
muscle cells from OPMD patients, it has been suggested that the mutated PABPN1 induces or
facilitates the formation of the inclusions. To gain insight into the mechanisms involved in
formation of OPMD nuclear inclusions, we generated green fluorescent protein (GFP) fusions
with PABPN1 variants. Our results show that, upon over-expression, PABPN1 aggregation
occurs in the absence of polyalanine expansion. Propensity of PABPN1 to form intranuclear
inclusions is coupled to stimulation of polyadenylation, and aggregation is a highly dynamic,
reversible process. Because transient transfection results in an uncontrollable, highly variable
level of PABPN1 gene expression, we constructed clones of C2 cells (an established murine
myoblast cell line derived from perinatal mouse skeletal muscle), stably transfected with wild
type or mutant human PABPN1. The resulting mRNA expression levels for normal and mutant
human PABPN1 ranged from 2 to 10-fold relative to the equivalent endogenous murine mRNA.
At these levels of expression, formation of intranuclear inclusions was not detected either in the
wild type or in the mutant PABPN1-containing clones. Thus, this provides a unique model to
study the cellular effects of the PABPN1 mutation before disorganisation of the nuclear
architecture.
Publications in International Journals (2004)
Lindberg, A., Gama-Carvalho, M., Carmo-Fonseca, M. and Kreivi, J.-P. (2004) A single RNA
recognition motif in splicing factor ASF/SF2 directs it to nuclear sites of adenovirus transcription.
J. Gen. Virol. 85:603-608. (Journal IF: 3.036)
Naderi, A., Ahmed, A.A., Barbosa-Morais, N.L., Aparicio, S., Brenton, J.D., Caldas, C. (2004)
Expression microarray reproducibility is improved by optimising purification steps in RNA
amplification and labelling. BMC Genomics 5:9 (http://www.biomedcentral.com/147-2164/5/9)
Berciano, M.T., Villagra, N.T., Ojeda, J.L., Navascues, J., Gomes, A., Lafarga, M., and Carmo-
Fonseca, M. (2004) Oculopharyngeal muscular dystrophy-like nuclear inclusions are present in
normal magnocellular neurosecretory neurons of the hypothalamus. Hum. Mol. Genet. 13:829-
838. (Journal IF: 8.597)
Custódio, N., Carvalho, C., Condado, I., Antoniou, M., Blencowe, B.J. and Carmo-Fonseca, M.
(2004) In vivo recruitment of exon junction complex proteins to transcription sites in mammalian
cell nuclei. RNA 10:622-633. (Journal IF: 4.430)
Pacheco, T.R., Gomes, A.Q., Barbosa-Morais, N.L., Benes, V., Ansorge, W., Wollerton, M.,
Smith C.W., Valcarcel, J., and Carmo-Fonseca, M. (2004) Diversity of vertebrate splicing factor
U2AF35: identification of alternatively spliced U2AF1 mRNAs. J. Biol. Chem. 279:27039-
27049. (Journal IF: 6.482)
Braga J., Desterro J.M., Carmo-Fonseca M. (2004) Intracellular macromolecular mobility

measured by fluorescence recovery after photobleaching with confocal laser scanning
microscopes. Mol. Biol. Cell 15:4749-4760. (Journal IF: 7.454)
Hematopoietic Biology Unit
In the Unit of Hematopoietic Biology we investigate the biological mechanisms underlying

normal and malignant human hematopoietic differentiation. Two main lines of research,
developed by two independent groups, are in progress:
Line I - (Hematopoiesis Group) – focuses on the role of Notch signalling in cell-fate decisions in
early human normal hematopoiesis.
Line II – (Tumor Biology Group) aims at investigating the role of microenvironmental factors in
the pathogenesis of T-cell leukemia and in normal human T-cell development.
Leonor Parreira, MD PhD – Full Professor, FML
Research Team
LINE I - Hematopoietic Differentiation

Hematopoiesis Group
Research Team
Leonor Parreira – PI (MD, PhD)

Hélia Neves – PhD student (Thesis concluded)
Isabel Alcobia – PhD student (Thesis concluded)
Ana Sofia Quina – PhD student (Thesis concluded)
Since October 2004 – Ornella Preisner – PhD student

Since March 2003 - Ana Paula Santos – Post-Doc
Since December 2004 – Andrea Santos – Post-Doc
The Hematopoiesis group is devoted to the study of Notch signaling effects in the differentiation
of hematopoietic stem cells. The experimental procedures are based on cell co-culture assays in
which the differentaiation of normal CD34+ cells proceeds in contact with bone-marrow derived
stromal cells forced to express distinct Notch ligands by retroviral transduction. Normal CD34+
cells are then cultured in contact with the modified stromal cells and, the effects on cell
differentiation, proliferation and death investigated, using phenotypic and functional assays.
Line II - Signal Transduction in T-cell leukemia and T-cell development

Tumor Biology Group
Research Team
Coordinator: João Taborda Barata, PhD – Post-Doc fellowship, FCT

Ana Silva – PhD fellowship, FCT
Bruno Cardoso – Undergraduate student, FCUL
Luís Bicheiro – Undergraduate student, FCUL
Luís Vinagre – Undergraduate student, FCUL
The Tumor Biology Group of the Hematopoietic Biology Unit aims to establish a dynamic
research vector on cancer biology, with particular emphasis on hematological malignancies.
There is mounting evidence that tumor cells interact with the surrounding environment in a bi-
directional manner that results in the acquisition of a competitive advantage by the malignant
cells. Therefore, cancer progression is not exclusively dependent on tumor cell-intrinsic
alterations. Currently, our research focuses on the role that factors produced by the
microenvironment might play in the pathogenesis of T-cell leukemia and in normal human T-cell
development.
Neves H, Ramos C, da Silva MG, Parreira A, Parreira L (1999) The nuclear topography of ABL,
BCR, PML, and RAR alpha genes: Evidence for gene proximity in specific phases of the cell
cycle and stages of hematopoietic differentiation. Blood 93: 1197-1207.
Alcobia I, Dilao R, Parreira L (2000) Spacial associations of centromeres in the nuclei of

hematopoietic cells: evidence for cell-type-specific organizational patterns Blood 95: 1608-1615.
Jaleco, A.C., Neves, H., Hooijberg, E., Gameiro, P., Clode, N., Haury, M, Henrique, D., and
Parreira, L. (2001) Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid
differentiation. Journal of Experimental Medicine 194:991-1001.
Barata, J.T., A.A. Cardoso, L.M. Nadler, V.A. Boussiotis (2001) Interleukin-7 promotes survival
and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the
cyclin-dependent kinase inhibitor p27kip1. Blood 98:1524-1531.
(Times cited: 21) (Journal IF in 2001: 9.273)
Parreira L, Neves H, Simoes S (2003) Notch and lymphopoiesis: a view from the
microenvironment. Seminars in Immunology 15: 81-89. (Times cited: 6) (Journal IF: 8.705)
Line I – Hematopoiesis Group
2001/05 Differential effects of Notch ligands Delta 1 and Jagged1 in lymphoid

differentiation. POCTI/BCI/37953/2001.
2003/06 Delta and Jagged genes in normal hematopoietic differentiation.

POCTI/BCI/37953/2001.
We wish to elucidate the role of Delta and Jagged genes, two "cell-fate" decision genes, in the
biology of human hematopoiesis. The rationale is the following: the choice between alternative
cell-differentiation pathways is regulated by direct intercellular contacts mediated by trans-
membrane proteins expressed by adjacent and apparently equivalent stem cells. Two protein
families involved in this process are the Notch receptors and their ligands, the Delta and Jagged
proteins. Both protein families are phylogenetically conserved and involved in several
developmental scenarios. We have established in our Lab a cell co-culture assay, in which bone-
marrow stromal cells were transduced with retroviral vectors containing the Delta1 or Jagged1 c-
DNA and used as feeder cell layers for the in vitro differentiation of normal human CD34+ cells.
We showed, for the first time, that Delta-1 inhibits the differentiation of human hematopoietic
progenitors into the B-cell lineage while promoting the emergence of cells with a phenotype of T-
cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either B- or T-cell/NK
development. Furthermore, cells cultured in the presence of either Delta-1 or Jagged-1 can
acquire a phenotype of NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de
novo cell population coexpressing CD4 and CD8 (J Exp Med, 2001, 194:991-1001).
Subsequently, we investigated the role of these same Notch ligands on myeloid development. To
do this we used long-term culture assays of CD34+ in transduced stromal cells followed by the
analysis of their differentiation potential in methylcellulose clonogenic assays. The results
indicate that Delta-1 and Jagged-1 differ as to their differential effects in myelopoiesis, namely on
the proliferation, clonogenic and differentiation properties of pluripotent myeloid precursors.
Furthermore, microarray analysis of precursors grown in the presence of Delta1 or Jagged1 have
different transcriptomes in what concerns cell-lineage affiliation programs and, also, the
molecular makeup responsible for the functional contacts between hematopoietic precursors and
their stromal environment.
Line II – Tumor Biology Group
2000/04 Targeting signaling pathways as therapy for human cancer

(POCTI/CBO/34914/00).
Our goal is to dissect the signaling pathways and characterize the cellular and molecular
mechanisms implicated in the acquisition of a selective advantage by malignant cells over their
normal counterparts. Ultimately, this will allow the identification of novel putative targets for
therapeutic intervention and the pre-clinical evaluation of agents that may effectively disrupt the
advantageous interactions of malignant cells with their microenvironment.
The identification of exogenous factors regulating leukemia expansion is one of the basic aims of
our research. We have analyzed the putative role in T-cell acute lymphoblastic leukemia (T-ALL)
of cytokines that signal through the common gamma chain (γc) - IL-2, IL-4, IL-7, IL-9 and IL-15,
and confirmed that all γc-signaling cytokines tested have the ability to promote the proliferation of
primary leukemia cells. IL-7 induced the most robust proliferative responses and was the cytokine
to which a higher number of patients were responsive. IL-4 preferentially stimulated the
proliferation of specimens with a more mature phenotype, whereas CD1a-positive cortical T-ALL
cells were less responsive to IL-9 than cells from other stages of maturation. We also observed
that combinations of two γc-signaling cytokines could have synergistic or additive proliferative
effects. Our studies showed, for the first time, that IL-9 and IL-15 stimulate T-ALL cells and
might be involved in the biology of the disease. Importantly, our data support the hypothesis that
IL-7 may function as a critical regulator of T-ALL in vivo.
The dissection of critical signaling molecules and the development of specific inhibitors are
limited by insufficient numbers of primary T-ALL cells and by their high rate of spontaneous
apoptosis. To circumvent these limitations, we managed to establish an IL-7-dependent T-ALL
cell line that we named TAIL7, which we demonstrated to be a biologically accurate surrogate for
primary leukemia T cells. Hence, TAIL7 may constitute a valuable tool for the study of the
signaling pathways implicated in T-ALL and the identification of molecular targets for the
rational design and validation of anti-leukemia signaling-inhibitors. We are currently using this
cell model to unravel IL-7 signaling mechanisms in T-ALL and study their importance in
leukemia expansion in vitro. TAIL7 cells will also be used to examine the role of IL-7 during
leukemia development in vivo, using chimeric mouse models of human T-cell leukemia.
MEK/Erk and PI3K/Akt(PKB) pathways have been shown to play active roles in normal T cell
expansion. Thus, we investigated the potential role of these pathways in IL-7-mediated signaling
in T-cell leukemia. IL-7 induced activation of MEK/Erk pathway in T-ALL cells; however,
inhibition of the MEK/Erk pathway by the use of the MEK-specific inhibitor PD98059 did not
affect IL-7-mediated viability or cell cycle progression of leukemia cells. IL-7 induced PI3K-
dependent phosphorylation of Akt/PKB and its downstream targets GSK-3, FOXO1 and
FOXO3a. PI3K activation was mandatory for IL-7-mediated Bcl-2 upregulation, p27kip1
downregulation, Rb hyperphosphorylation, and consequent viability and cell cycle progression of
T-ALL cells. Moreover, PI3K was also critical for maintenance of mitochondrial homeostasis,
Glut1 expression, glucose utilization and cell size increase mediated by IL-7. Overall, our results
implicate PI3K as a major effector of IL-7-induced viability, metabolic activation, growth and
proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent
molecular targets for therapeutic intervention in T-ALL. We are currently evaluating whether
particular PI3K downstream substrates, such as Akt/PKB, PKC, PKA, ILK, or mTOR are
selectively involved in particular effects.
Barata, J.T., T.D. Keenan, A. Silva, L.M. Nadler, V.A. Boussiotis, A.A. Cardoso (2004)
Common Gamma Chain-Signaling Cytokines Promote Proliferation of T-Cell Acute
Lymphoblastic Leukemia. Haematologica 89:1459-1467. (Journal IF: 3.453)
Barata, J.T., A. Silva, J.G. Brandão, L.M. Nadler, A.A. Cardoso, V.A. Boussiotis (2004)
Activation of PI3K is Indispensable for Interleukin 7-Mediated Viability, Proliferation, Glucose
Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells. Journal of Experimental
Medicine 200:659-669. (Journal IF: 15.340)
Barata, J.T., V.A. Boussiotis, J.A. Yunes, A.A. Ferrando, L.A. Moreau, J.P. Veiga, S.E. Sallan,
A.T. Look, L.M. Nadler, A.A. Cardoso (2004) IL-7-dependent human leukemia T-cell line as a
valuable tool for drug discovery in T-ALL. Blood 103:1891-1900. (Journal IF: 10.120)
Chromatin Biology Unit
The main objective of the Chromatin Biology Unit is to expand our current knowledge on the
biology of human topoisomerases, the enzymes that regulate DNA topology, within the context of
other nuclear activities. We are particularly focused in understanding how topoisomerases
participate in the replication and maintenance of chromatin structure with implications on cellular
epigenetic memory. We are also interested in disclosing how topoisomerases cooperate with other
cellular machineries, namely those involved in transcription and DNA repair, to ensure proper
maintenance of genome integrity. These latter issues are being addressed in the context of cancer
chemotherapy with topoisomerase targeting drugs.
João Ferreira, MD, PhD – Auxiliary Professor, FML
Research Team
Soren Steffensen (Jan-Sept 2004), PhD – Post-Doc Fellowship, FCT

Marta Agostinho, MSc – PhD Fellowship, FCT
Fernando Ferreira – Assistant, FMV
Research Areas
Cell and Molecular Biology

Topoisomerase function
Chromatin structure and organization
Cancer
Ferreira, J., Paolella, G., Ramos, C. and Lamond, A.I. (1997) Spatial organization of large-scale
chromatin domains in the nucleus: a magnified view of single chromosome territories. J. Cell
Biol. 139:1597-1610. (Times cited: 98) (Journal IF: 12.5)
McKendrick, L., Thompson, E., Ferreira, J., Morley, S.J. and Lewis, J.D. (2001) Interaction of
eukaryotic translation initiation factor with nuclear cap-binding complex provides a link between
nuclear and cytoplasmic functions of the m7 guanosine cap. Mol. Cell Biol. 21:3632-3641.
Carvalho, C., Pereira, H.M., Ferreira, J., Pina, C., Mendonça, D., Rosa, C., and Carmo-Fonseca,
M. (2001) Chromosomal G-dark bands determine the spatial organization of centromeric
heterochromatin in the nucleus. Mol. Biol. Cell 12:3563-3572.
Agostinho, M., Rino, J., Braga, J., Ferreira, F., Steffensen, S. and Ferreira, J. (2004) Human
topoisomerase IIα: targeting to subchromosomal sites of activity during interphase and mitosis.
Mol. Biol. Cell 15:2388-2400. (Times cited: 2) (Journal IF: 7.454)
Poot, R., Bozhenok, L., van den Berg, D.L.C., Steffensen, S., Ferreira, F., Grimaldi, M., Ferreira,
J. and Varga-Weisz, P. The Williams Syndrome Transcription Factor Interacts with PCNA to
Target Chromatin Remodeling by ISWI to Replication Foci. Nature Cell Biology, Epub ahead of
print, 14 Nov 2004. (Times cited: 0) (Journal IF: 20.268)
2000/04 Cell Biology of Human topoisomerase IIa. Fundação para a Ciência e a

Tecnologia (POCTI/BCI/36194/99)
2004/06 Implementation of a screening assay to predict clinical response to topoisomerase

I inhibitors (Fundação Calouste Gulbenkian/2004)
We have recently developed a new methodology that allows the identification, with subcellular
resolution, of sites of catalytic activity of topoisomerases inside the cell nucleus. Employing this
novel assay, termed DRT (Differential Retention of Topoisomerase), it was shown that
catalytically active topoisomerase IIa concentrates over heterochromatin during its time of
replication in late S phase (Agostinho et a; Mol Biol Cell, 2004). Since topoisomerase II interacts
with chromatin remodeling and modification activities (eg, histone deacetylases) involved in the
biogenesis and maintenance of the heterochromatic state, we are currently addressing whether
topoisomerase II plays a role in these processes. This will tell whether topology restoration
machineries are involved in conveying epigenetic memory that is encrypted in chromatin
structure.
As discriminated above, topoisomerase II interacts with chromatin remodeling factors namely the
WSTF transcription/remodeling factor. In a collaborative study with the group of Dr. Patrick
Varga-Weisz we could show that WSTF concentrates at sites of DNA replication to establish
proper reproduction of chromatin structure through successive cell generations (Poot et al;
Nature Cell Biol, 2004). We are now testing whether topoisomerase II cooperates with WSTF in
replication of chromatin structure.
During adenovirus infection of human cells several host factors, including topoisomerases, are
recruited to sites of adenovirus replication/transcription termed viral “factories”; utilizing the
DRT assay we have shown that factories correspond to sites of privileged catalytic activity of
topoisomerases (type I and II). We are employing this model system to (1) underscore whether
replication and transcription activities are required for the recruitment of topoisomerases to
factories, to (2) elucidate which domains of the topoisomerase (type I and II) molecules are
essential for their targeting to factories, and (3) whether type I and type II topoisomerases play a
differential role in the replication of the viral genomes. These results are expected to expand our
knowledge of some basic aspects of the biology of topoisomerases namely the differential roles
played by type I and II enzymes.
Topoisomerases (types I and II) are important targets in the chemotherapy of cancer. Our group is
involved in a collaborative study with Prof. Luis Costa (Department of Oncology, Hospital Santa
Maria) to address the mechanisms underlying the emergence of resistance to drugs targeting
topoisomerase I throughout the course of chemotherapy for colon cancer.
Agostinho, M., Rino, J., Braga, J., Ferreira, F., Steffensen, S. and Ferreira, J. (2004) Human
topoisomerase IIα: targeting to subchromosomal sites of activity during interphase and mitosis.
Mol. Biol. Cell 15:2388-2400. (Journal IF: 7.454)
Poot, R., Bozhenok, L., van den Berg, D.L.C., Steffensen, S., Ferreira, F., Grimaldi, M., Ferreira,
J. and Varga-Weisz, P. (2004) The Williams Syndrome Transcription Factor Interacts with PCNA
to Target Chromatin Remodeling by ISWI to Replication Foci. Nature Cell Biology, Epub ahead
of print, 14 Nov 2004. (Journal IF: 20.268)
Developmental Biology Unit
The main objective of the Developmental Biology Unit is to to investigate the molecular
mechanisms that regulate the production of nerve cells in vertebrate embryos. We have a
particular interest in two aspects of the process:
1. The role of the Delta/Notch signalling pathway in cell fate decisions within the
developing nervous system and
2. The establishment of neuroepithelial cell polarity and its influence on neuronal

development.
In the first case, we want to study how the activity of the Notch pathway contributes to the
regulation of neuronal production, from the initial establishment of neural precursors in the
embryo until the appearance of fully differentiated neuronal cells. In the second case, we want to
study how cell polarity is established in the embryonic neural epithelium and how it contributes
to cell fate decisions during neural development.
We are studying these processes in chick and mouse embryos, taking advantage of our experience
with manipulating gene activity in these animal models, using both loss- and gain-of-function
approaches. We also use Embryonic Stem (ES) cells as an in vitro model of neural commitment
and differentiation, not only because it is a simple and more controlled cellular system, but also
because of their potential applications in regenerative medicine.
Our main aim is to provide a better understanding of the processes of in vivo neural commitment
and differentiation, and translate this knowledge to the production in vitro of neural precursors
and differentiated neurons from ES cells, which may be used in the future for cell therapy of CNS
disorders.
Domingos Henrique, PhD – Auxiliary Professor, FML
Research Team
Evguenia Bekman, PhD - Post-Doc Fellowship, FCT

Susana Lopes, PhD - Post-Doc Fellowship, FCT
Cláudia Valente, PhD - Post-Doc Fellowship, FCT
Rita Fior - PhD Fellowship, FCT
Cristina Afonso - PhD Fellowship, FCT
Gonçalo Neto - PhD Fellowship, FCT
Susana Rocha – Graduate Student, FCUL
Manuel Baptista – Graduate Student, FCUL
Alina Sequeira Costa – Technician
Research Areas
Cell and Molecular Biology of Notch signalling

Generation of Neural Stem Cells
Neurogenesis
Campos, L., Duarte, A., Branco, T., Henrique, D. (2001) Dll1 and Dll3 expression in the
developing brain: a role in the establishment of the cortical structure. J. Neurosci. Res. 64:590-8.
Henrique, D., Schweisguth, F. (2003) Cell Polarity: the ups and downs of the Par6-aPKC
complex. Current Oppinion on Genetics & Development 13:341-350.
Kawakami, Y., Rodríguez-León, J., Koth, C., Büschen, D., Itoh, T., Raya,A., Ng, J., Esteban, C.,
Henrique, D., Takahashi,S., Asahara, H., Belmonte, JC. (2003) MKP3 Mediates the Cellular
Response to FGF8 Signalling in the Vertebrate Limb. Nature Cell Biology 5:513-19.
Duarte, A.., Hirashima, M., Benedito, R., Trindade, A., Diniz, P., Bekman, E., Costa, L.,
Henrique, D., and Rossant, J. (2004) Dosage-sensitive requirement for mouse Dll4 in artery
development. Genes&Development 18:2474-2478. (Times cited: 1) (Journal IF: 17.013)
2001/04 “Eurostem – Neural Stem Cells and Stem-Cell Therapies” (QLG3-CT-2000-

01224)
2003/06 “Characterization of vertebrate prickle-like genes and their functional role during
embryonic development” Fundação Ciência e Tecnologia, (POCTI 48783/02).
2004/07 “Expansion and differentiation of Neural Stem Cells in Bioreactors”

(POCTI/BIO/46695/02). Joint Project with Prof. Joaquim Cabral, I.S.T., Lisboa.
2004/07 “FunGenES- Functional Genomics in Engineered ES cells”, 6th Framework

Integrated Project.
Recent Work
In vertebrates, neurogenesis starts very early during embryonic life and the majority of neurons is
produced before birth. A general picture is emerging about the molecular mechanisms regulating
the initial steps in the determination of neural cells in vertebrates. And from all these studies it
seems that vertebrates and flies employ a similar and conserved genetic circuitry, comprising the
action of both proneural and neurogenic genes, to regulate the production of neurons during
embryonic development. However, it is clear that the repertoire of genes participating in this
circuitry have expanded in vertebrates, resulting in the acquisition of further levels of regulation
and consequent increase in complexity. Identifying the various components of this genetic
circuitry and how they regulate the establsihment of neural precursors and their commitment to
neurons is the main aim of our work.
Our recent work has focused on two main areas: the function of the Delta/Notch signalling
pathway during neurogenesis and how cell polarity is established in the developing neural
epithelium. We have also done some work on the role of Notch signalling during vasculogenesis
and endothelial cell differentiation.
Concerning the first area, we have isolated and characterized several new components of the
Notch pathway in vertebrates and are trying to unravel their function during neural development.
We have been analysing the role, during retinal neurogenesis, of a newly characterized Delta gene
(Delta-4), which encodes a ligand for the Notch receptor. A careful analysis of Delta-4
expression in the developing chick retina indicates that this gene is expressed in nascent neurons,
when they are migrating out of the proliferative region of the neuroepithelium. By comparing the
expression of Delta-1 and Delta-4 (the two Notch ligands expressed in the vertebrate retina), we
have found that the expression of Delta-1 in newly born neurons precedes that of Delta-4, and
that Delta-1 is expressed in a larger proportion of these cells. This suggests that a fraction of the
newly born neurons in the developing retina (chick and mouse) express sequentially these two
related Notch ligands, first Delta-1 and then Delta-4.
While our previous work has shown that Delta-1 mediates a signal from nascent neurons to
dividing neural progenitors in the retina, thus preventing these cells from exiting the cell cycle
and enter differentiation prematurely, we have however failed to find evidence that Delta-1 is
directly involved in the generation of distinct cell types by the differentiating retinal neurons.
Given our findings on the sequential expression of Delta-1 and Delta-4 in newborn neurons, our
working hypothesis is that the main role of Delta-4 would be to mediate interactions between
differentiating (post-mitotic) neurons to force these cells to adopt distinct cell fate decisions.
Different Notch ligands could therefore be used in a sequential way to control unique aspects of
vertebrate neurogenesis.
In order to test this and other aspects of Delta-4 function, we have generated a targeted mutation
on the mouse Delta-4 gene. However, this produces an early lethal embryonic phenotype, due to
vascular malformations (see below), precluding analysis of Delta-4 function in the nervous
system. To circumvent this limitation, we are creating a conditional knock-out of Delta-4, in
collaboration with A. Duarte (Lisbon Veterinary School).
Nonetheless, we have used heterozygous Delta-4 (+/-) mice, and also heterozygous Delta-1 (+/-)
mice, to study in detail the expression of the Delta genes in the developing mouse retina. These
mice contain an insertion of a reporter LacZ into the endogenous Delta-1 and Delta-4 genes,
faithfully mimicking their normal expression. By following the production of ß-galactosidase in
heterozygotes, we were able to show that Delta-1 expressing cells become neurons and are in
close contact with radial glial cells, probably modulating the fate of these cells, as sugested
recently by other studies where Notch signalling was constitutively activated in radial glia
(Campos., L. et al 2001). We have also shown that Delta-4 expressing cells in the retina are able
to differentiate into each of the neuronal cell types produced, from ganglion cells to
photoreceptors (Susana Lopes). This suggests that Delta-4 is active in nascent neurons, and is
compatible with working hypothesis that this gene mediates interactions between differentiating
neurons to force these cells to adopt distinct neuronal fates.
We have also isolated various chick and mouse homologues of the Drosophila Enhancer of Split
genes, named HES (hairy and Enhanceer of split homologues), which are known to encode a
group of related proteins with a DNA-binding domain of the bHLH class and act as
transcriptional repressors to mediate Notch activity. We have analysed the expression pattern of
these genes and found that they are expressed in several embryonic tissues where Notch receptors
are known to be present and active, namely the retina, neural tube, muscle precursors and the
arterial vascular system. Functional analysis of the role of HES genes have been performed in the
chick neural tube, using electroporation to misexpress wild-type and putative dominant-negative
forms of the HES proteins. We have found that chick HES genes are important players of the
Notch signalling pathway that control vertebrate neurogenesis. More specifically, we have
identified a conserved genetic network of cross-regulatory interactions between the hes5 and hes6
genes, which we propose have a central role in the pulses of Notch activity that control the
maintenance of a pool of neural progenitors in the developing nervous system (Rita Fior,
submitted).
During our expression studies, we have found that both Delta-4 and some HES genes have a
striking expression in the developing vascular system. This highlights a function of Notch
signalling during endothelial differentiation and to understand better this function we have
proceeded to a careful analysis of the expression of these genes in the vascular system. We have
found that both genes are expressed preferentially in endothelial cells of the arteries and not
veins, in particular during the process of sprouting. We have misexpressed Delta-4 in developing
veins and have shown that this is enough to produce a vein-to-artery transformation (A. Manaia,
in preparation). In addition, analysis of Delta-4 mutant mice (done in collaboration with Janet
Rossant’s lab, Toronto) reveals that Delta4 signalling is necessary in arteries to maintain their
identity during development (Duarte, A. et al., Genes&Development 2004). Together, these
results demonstrate that Delta4-mediated Notch signalling is necessary and sufficient to the
acquisition of different bllod vessels identities during endothelial development. This work is
being continued in A. Duarte’s lab, at Lisbon Veterinary School, where he moved after his post-
doc in the lab.
Concerning the other research topic of the lab, the establishment of cell polarity in neuroepithelial
cells and how it contributes to cell fate decisions during neural development, we have focused our
attention on a particular protein complex, the Par3-Par6-aPKC complex. This is known to be one
of the major players in controlling the establishment of cell polarity, from C.elegans to
vertebrates (reviewed in Henrique & Schweisguth, 2003). We have isolated several chick
homologues of the C. elegans par-3 and par-6 genes, which encode PDZ proteins, and studied
their expression during neural development. Using antibodies against PAR-3, PAR-6 and aPKC,
we have shown that this complex is located at the apical junctions of neuroepithelial cells, where
it coincides with several other junctional proteins (like N-Cadherin and ß-catenin, for instance).
To study the function of this protein complex during neural development, we have used gain-of-
function assays in the developing chick neural tube, by electroporating different constructs
encoding PAR3 and PAR6 proteins. Our findings suggest that PAR3 is a scaffolding protein that
is able to assemble the whole complex and trigger the process of apical junction formation,
thereby establishing the correct apico-basal polarity of neuroepithelial cells (Cristina Afonso, in
preparation). We have shown that misexpression of PAR3 in these cells creates ectopic assembly
points for the complex at various points of the cell membrane, resulting in ectopic junctional
complexes that alter the normal apico-basal polarity of the cells. As a result, neuroepithelial cells
form epithelial-like structures – “rosettes” - within the neural epithelium but, surprisingly,
neurogenesis is not altered in these cells. Biochemical analysis of the interactions between the
PAR proteins and other protein complexes known to be important for apico-basal polarity,
allowed us to establish a framework hypothesis to explain the functions of the PAR complex. We
are currently testing this hypothesis.
The genetic dissection of the mechanisms regulating neurogenesis in mammals has been
hampered by the complexity of the mammalian brain and by the lack of a simple system to
analyse the generation of neural precursor cells. As a complementary approach to the studies
described above, we have established an in vitro culture system in which ES cells can be driven
through a process of controlled differentiation into committed neural precursors. We are using a
method developed in Dr. Austin Smith's lab (CGR, Edinburgh) for producing neural precursor
cells from ES cells, capable of generating various populations of fully differentiated neurons and
glial cells in culture. Using this culture system, we have started a “protein-trap” screen to identify
new molecules that show polarized distribution in neural precursor cells. This screen is based on
the random integration of reporter constructs (“protein-trap vector”, a modified version of the
classical "gene-trap vector") into the ES cell genome and subsequent monitorization of the fusion
protein derived from the "trapped" gene, which should reflect the normal cellular distribution of
the endogenous protein. We expect that the isolation of new proteins with polarized localization
in either neural precursors or differentiating neurons, followed by their functional
characterization, can lead to new insights into how cell polarity and cell fate are regulated in the
vertebrate nervous system.
Future Work
We shall pursue our analysis of Delta-1 and Delta-4 function in the retina, exploiting our current
model that these two genes act sequentially to control first the decision to become a neuron and,
second, to ensure that these neurons acquire different fates. We shall use conditional Knock-out
mice where the function of these genes are eliminated only in the retina, together with conditional
Knock-out mice for the Notch-1 gene, which is the only Notch receptor expressed in the retina.
We shall also use gain- and loss-of-function studies in the chick retina, ectopically expressing
Delta-1 and Delta-4 in a time controlled manner, by electroporating constructs that encode the
respective proteins. Recently, we succeeded in obtaining RNAi phenotypes with high efficiency
in the chick embryo (Susana Rocha) and plan to use this technique extensively in the chick to
generate loss-of-function studies for the genes we are studying.
We shall follow our studies on the hes5/hes6 circuitry, trying to understand precisely how the
network of negative cross-regulations between these genes work and how it contributes to the
generation of pulses of Notch activity in neural progenitors.
We shall continue our studies on neuroepithelial polarity, trying to understand how the PAR
complex triggers the establishment of apical junctions in neuroepithelial cells and how this leads
to the normal apico-basal polarity of these cells. Whether this polarity has an effect on the
production of neurns is still an open question that we would like to pursue.
We shall apply the knowledge about the molecular controls and mechanisms that regulate
neurogenesis in the embryo to try to devise new strategies to efficiently produce neural
percursors and/or neurons from ES cells, which can be used for transplantation studies in cell
therapy for CNS disorders.
Alsina, B., Abelló, G., Ulloa, E., Henrique, D., Pujades, C., Giraldez, F. (2004) FGF signalling is
required for determination of otic neuroblasts in the chick embryo. Dev. Biology 267:119-134.
(Journal IF: 5.351)
Duarte, A., Hirashima, M., Benedito, R., Trindade, A., Diniz, P., Bekman, E., Costa, L.,
Henrique, D., and Rossant, J. (2004) Dosage-sensitive requirement for mouse Dll4 in artery
development. Genes&Development 18:2474-2478. (Journal IF: 17.013)
Reproduction Biology Unit
Our unit is focused on the on the study of ovarian follicle and oocyte development, in particular
regarding cell-cell and cell-matrix interactions.
Specifically, we are interested in:
1. The establishment of in vitro and in vivo models of follicular differentiation.

2. The identification of cytological markers of both cytoplasmic and nuclear oocyte
competences and
3. The analysis of trans-zonal cell communication following criopreservation protocols
of ovarian tissue.
Carlos E. Plancha, MD, PhD - Auxiliary Professor, FML
Research Team
António J. Cidadão, MD, PhD - Associate Professor, FML

José E. Gomes, Biologist - PhD Fellowship, FCT
Alexandra Sanfins - PhD Fellowship, FCT
Patrícia Rodrigues - PhD Fellowship, FCT
Paulo Navarro-Costa, Biologist - PhD Fellowship, FCT
Ana Catarina Martins, Biologist - GRICES-INSERM Fellowship
Nuno Cortez-Dias - Medical student, GAPIC Fellowship, FML
Mafalda Rato - Biologist, FCUL
Sara Pimentel - Biology diploma thesis student, FCUL
Viviana Durão - Biology diploma thesis student, FCUL
Rita Marques - Biology diploma thesis student, FCUL
Ana Catarina Rita - Biology diploma thesis student, FCUL
Research Areas
Our unit is focused on the on the study of ovarian follicle and oocyte development, in particular
regarding cell-cell and cell-matrix interactions.
Specifically, we are interested in:
1. The establishment of in vitro and in vivo models of follicular differentiation.

2. The identification of cytological markers of both cytoplasmic and nuclear oocyte
competences and
3. The analysis of trans-zonal cell communication following criopreservation protocols of
ovarian tissue.
Gomes, J.E., S.C. Correia, A. Gouveia-Oliveira, A.J. Cidadão, C.E. Plancha (1999) Three-
dimensional environments preserve extracellular matrix compartments of ovarian follicles and
increase FSH-dependent growth. Molecular Reproduction and Development 54:163-172.
Gomes, J.E., A. Pesty, A. Gouveia-Oliveira, A.J. Cidadão, C.E. Plancha, B. Lefèvre (1999) Age
and gonadotropins control Ca2+-spike acquisition in mouse oocytes isolated from early preantral
follicles. The International Journal of Developmental Biology 43:839-842.
Martins, O.G., A. Pesty, A. Gouveia-Oliveira, A.J. Cidadão, C.E. Plancha, B. Lefèvre (2002)
Oocyte Ca2+-spike acquisition during in vitro development of early preantral follicles: influence
of age and hormonal supplementation. Zygote 10:59-64.
Sanfins, A., G.Y. Lee, C.E. Plancha, E.W. Overstrom, D.F. Albertini. (2003) Distinctions in
meiotic spindle structure and assembly during in vitro and in vivo maturation of mouse oocytes.
Biology of Reproduction 69:2059-2067. (Times cited: 4) (Journal IF: 3.646)
Sanfins, A., C.E. Plancha, E.W. Overstrom, D.F. Albertini (2004) Meiotic spindle morphogenesis
in in vivo and in vitro matured mouse oocytes: insights into the relationship between nuclear and
cytoplasmic quality. Human Reproduction 19:2889-2998. (Times cited: 0) (Journal IF: 3.125)
2001/04 Follicular quality evaluation following cryopreservation of ovarian tissue,

Foundation for Science and Technology (FCT), POCTI PROGRAM (POCTI /
ESP / 43628 / 2000).
Our major goal with this project is to characterize the effects of freezing/thawing of ovarian tissue
upon the viability, growth and maturational capacity of mouse and human pre-antral ovarian
follicles. So far, we characterized the role of oocyte-granulosa cell interactions in cultures of
granulosa cell-oocyte complexes and established appropriate three-dimensional culture conditions
for the growth and differentiation of isolated whole ovarian follicles. In addition we are also
interested in the analysis of transzonal granulosa cell projections in fully grown GV oocytes
following cryopreservation protocols of whole ovaries (mouse), as well as of follicular
development in culture following cryopreservation of half ovaries (mouse).
Sanfins, A., C.E. Plancha, E.W. Overstrom, D.F Albertini (2004) Meiotic spindle morphogenesis
in in vivo and in vitro matured mouse oocytes: insights into the relationship between nuclear and
cytoplasmic quality. Human Reproduction 19:2889-2998. (Journal IF: 3.125)
Félix, A., Rosa, J.C., Fonseca, I., Cidadão, A.J., Soares, J. (2004) Pleomorphic adenoma and
carcinoma ex pleomorphic adenoma - immunohistochemical demonstration of the association
between tenascin and malignancy. Histopathology 45(2):187-92. Journal IF: 2.952)
Vascular Pathobiology Unit
The aim of the Vascular Pathobiology Unit is to investigate the molecular mechanism underlying
the microvascular endothelial cell key roles in the regulation of blood tissue exchange. Molecular,
biochemical and hemorheological properties of blood components and its interaction with itself
and the vascular wall are the objectives of our research.
Experimental intravital microscopy animal model, combined with fluorescence microscopy and
spectroscopic and immunohistochemical staining studies in cell culture, white and red blood cells
as the “in vitro” models altogether, provide results for the knowledge of the mechanisms at
normal and several inflammatory conditions. These, in clinical situations such as chronic venous
disease, myocardial infarction, hypertension, kidney transplant, systemic lupus erythematosus,
and delirium in acute stroke could be “ex vivo” evaluated by hemorheological parameters and
endothelial functional markers by enzyme immune assay. We are specially interested in realize
how some vasomotors and pro inflammatory compounds act at cellular level and also to
understand how membrane biomolecular signals expression, second messengers, transcription
factors, and secreted factors could be related with the macro and microvascular diseases.
Carlota Saldanha, PhD-Associated Professor/João Martins e Silva, MD, PhD-Full Professor
Research Team
Nuno C. Santos – Auxiliary Professor, FML

João Martin Martins – Auxiliary Professor, FML
Ângelo Calado – Auxiliary Professor, FML
Henrique Sobral do Rosário – Assistant, FML
Filomena Carvalho – Assistant Intern, FML
Luís Sargento – Invited Assistant until 2000; Cardiology Independent Investigator since 2001
Leyre Zabala – Invited Assistant, FML
Sandra Hilário – Invited Assistant, FML
Sónia do Vale – Invited Assistant, FML
Ana Santos Silva – Undergraduate Degree Thesis since 2002
Sandra Garcês – Monitor, FML
Tiago Santos - Monitor, FML
Sónia Abreu – PhD student since 2002
Ana Bia – Medical student, FML
Rodrigo N.B. Ramos – Medical Student, FML
Research Areas
Cell and molecular biochemistry

Hemorreology
Microcirculation
Vascular pathobiology
Zabala, L., Saldanha, C., Martins e Silva, J., Souza-Ramalho, P. (1999) Red blood cell membrane
integrity in primary open angle glaucoma: “ex vivo” and “in vitro” studies. Eye 13:101-103.
Sobral do Rosário, H., Saldanha, C., Martins e Silva, J. (1999) Increased leukocyte-endothelial
interaction in the mesenteric microcirculation following remote ischemia-reperfusion.
Microvascular Research 57:199-202. (Times cited: 2) (Journal IF: 1.858)
Sargento, L., Zabala, C., Saldanha, C., Sousa-Ramalho, P., Martins e Silva, J. (1999) Sodium
fluorescein influence on the hemorheological profile on non-insulin dependent diabetes mellitus
patients. Clin. Hemorheol. Microcirc. 20:77-84. (Times cited: 3) (Journal IF: 0.833 )
Santos, N.C., Figueira-Coelho, J., Saldanha, C., Martins-Silva, J. (2002) Biochemical, biophysical
and haemorheological effects of dimethylsulphoxide on human erythrocyte calcium loading. Cell
Calcium 31: 183-188. (Times cited: 4) (Journal IF: 3.287)
Saldanha, C., Santos, N.C., Martins e Silva, J. (2002) Fluorescent probes DPH, TMA-DPH and
C17-HC induce erythrocyte exovesiculation. J. Membrane Biol. 190:75-82.
Sargento, L., Saldanha, C., Monteiro, J., Perdigão, C., Martins e Silva, J. (2003) Evidence of
prolonged disturbances in the haemostatic, hemorheologic and inflammatory profiles in
transmural myocardial infarction survivors. A 12-month follow-up study. Thromb. Haemost.
89:892-903. (Times cited: 2) (Journal IF: 4.95 )
1999/04 “Functional characteristics of erythrocyte and lymphocyte membranes in HIV-1

infected patients”. Comissão Nacional da Luta contra a SIDA
2001/06 “Mathematical and numerical modeling of the human cardiovascular system”

(FCT-POCTI/MAT/41898/2001)
2002/05 “Fibrinogen interaction with the erythrocyte membrane” Fundação Calouste

Gulbenkian.
2002/05 “Non cholinergic action of acetylcholine in endothelial cells”. INFARMED
2003/04 “NO effects in signal transduction pathway protein band 3 tyrosine kinase
dependent in human erythrocytes”. GAPICTI, FML.
2003/04 “Non neuronal effect of acetylcholine in lymphocyte signal transduction pathway

mediated by acetylcholinesterase”. GAPICTI, FML.
2004/05 “Telepathic behavior associated with biochemical and neuroendocrine

parameters”. Fundação Bial.
2004 “Clinical Study with phytosterols in milk”. Centro de Nutrição e Alimentação

Mimosa.
The research in our Unit started (1976) with the metabolic and tissue oxygenation parameters
evaluated in experimental and clinical hypoxia situations. At those same conditions
hemorheological studies were conducted (since 1984). The results obtained rised many questions
about signal transduction mechanisms that developed at the blood endothelial interface. The
binding of circulating cells to the vascular wall play a key role in inflammation, metastasis and
therapeutic cell delivering. The rheology of blood can influence the binding of blood cells to
endothelial cells and, consequently, modify the oxygenation environment as well as pro and anti
coagulation factors (or at variation fibrinolitic factors) and exocytose of proinflammatory
cytokines. It was verified the anti-inflammatory effect of acetylcholine in rat’s systemic
inflammatory response to endotoxin. We are interested in understanding how lymphocytes and
endothelial cells release acetylcholine and why and in what conditions it appeares at blood flow.
What repercussions occurred in erythrocyte, lymphocyte and endothelial cells at membrane level
(specific receptors and enzyme the acetylcholinesterase), at intracellular medium (identification
of second messenger, NO, Ca2+, proteins cascade reaction and transcription factors) in the
presence of acetylcholine and other vasomotor compounds and chemical or physical stress
conditions.
Report of ongoing projects mentioned above
Current results obtained, with models similar to the mentioned above, at molecular
intercommunications levels, are leading to mathematical modelling of cell shape, movements,
fluid and surface forces involved in blood cell-endothelial interactions. Glaucoma patients are
submitted to retinal blood flow evaluation by the oftlamological team (Professor Metzler Serra
and Dr Cristina Freire) and blood samples were collected from forearm vein to hemorheological
parameters determinations by our Unit. The results are used for mathematical modelling for
simulation vascular bed by the IST Group (Professor Adélia Sequeira).
Hemorheological parameters evaluation has been done in blood samples collected from forearm
veins of patients with systemic lupus erythematosus (SLE) in collaboration with the team of
Professor Viana de Queiros. Some patients with SLE develop cardiovascular diseases with or
without atherosclerotic plaques, according to their SLE disease activity index (SLEDAI).
We are interested in testing if there are some kind of association between any hemorheological
parameter and the SLEDAI. At the moment, we still have not enough results to perform any
evaluation.
There are clinical evidence that fibrinogen is an acute phase protein which levels are raised at
inflammatory situations and induced increased platelet and erythrocyte aggregation. The binding
site for platelet is well defined but the same is not true for erythrocytes. Also it is still unknown
how fibrinogen promote erythrocyte aggregation, in spite of two theoretical models that were
described. We are aware for this question and our previous “in vitro” study show us an impaired
erythrocyte aggregation in presence of β-estradiol when fibrinogen concentrations were not

changed. We start binding study evaluations using intrinsic tryptophan fluorescence to obtain
information on the conformational changes of the fibrinogen protein upon interaction with β-
estradiol. The quenching parameters values obtained at different β-estradiol concentrations and
with different charged and uncharged quenchers show alterations that could be related with
conformational changes or discrete tryptophan residues reorganization during fibrinogen binding.
These results need further experimental studies to give some light to the fibrinogen erythrocyte
binding process.
A clinical study has been conducted with hypercholesterolemic subjects submitted to enriched
milk with phytosterols (2g/day) during a month after their informed consent for the study , and
which was approved by the ethic commission of the FML, UL. The patients were followed by
Professor Vasco Maria team at Cacém Health Centre. The hemorheological parameters such as
erythrocyte aggregation index, hematocrit and plasma viscosity did not change after a diet
enriched with milk with phytosterol and β-carotene plasma content was maintained, but plasma
total cholesterol and LDL-cholesterol decreased significantly (p<0.05) after 15 and 30 days of
milk intake that
A similar study was hold with 40 Wistar rats divided in 4 experimental groups drinking milk with
different phytosterols concentrations. The results showed that there were no significantly growth
changes besides the significantly decreased (p<0.0001) LDL cholesterol plasma concentrations.
Blood flow variations was observed in rabbits submitted to experimental telepathy which also
reported the presence of spontaneous fear as pointed by René Peoc´h (Institute International d
Ìmmunologie, Bouguenais, France). We were interested to verify if a stress stimulus occur
responsible for the neuronal hypersensitivity. Experimental telepathy was performed by Peoc`h
research team and blood samples were send to our Unit. It was verified a bradycardia effect,
induced by telepathic fear transmission that was followed by a significant decrease of plasma
cortisol levels and absence of plasma TNF-α concentrations variations as well as rabbit
erythrocyte membrane integrity (acetylcholinesterase enzyme activity unchanged) maintained.
We raise the hypothesis that the limbic system might be acting in order to limit the telepathy
response with glucocorticoid receptors saturated at the hippocampus level which will be studied
in the next accepted project by Fundação Bial 2004/2005 to be initiated at February 2005.
The erythrocytes and lymphocytes of patients with HIV-1 were studied regarding membrane
properties and intracellular calcium concentrations using fluorescent probes. The study has the
collaboration of the Professor Francisco Antunes research team which followed the patients
previously to their engagement in antirectoviral therapy. Similarly decreased membrane fluidity
was observed both in erythrocyte and lymphocyte membranes of infected patients, with opposite
variations in calcium changes with increased levels at lymphocytes and lower content at
erythrocytes in relation to values of healthy subjects. Erythrocyte acetylcholinesterase enzyme
activity has normal values and shown lower ones in lymphocytes of HIV-1 patients. Our data
shows that HIV-1 infection leads to biochemical and biophysical changes on the membrane itself
and on membrane enzyme activity in lymphocytes and erythrocytes. Our observations are
consistent with a process of facilitated propagation of the infection to new cells, and maintenance
of a reservoir of erythrocyte-bound infectious virus.
Regarding the non cholinergic action of acetylcholine (ACh) our results performed with human
umbilical endothelial cells (HUVECs) showed that there is an increased production of nitric oxide
(NO) measured with an NO electrode (electrochemical method) when acetylcholine is present in
HUVECs cultures. When the acetylcholinesterase inhibitor velnacrine is present there is a
decrease on the NO produced and also impaired values are obtained when both substrate and
inhibitor are present. We raise the hypothesis that acetylcholinesterase when either in an active
complex form or in an less active complex form could be a key protein in the signal transduction
mechanism mediated by acetylcholine with NO as the second messenger (the studies are
ongoing). We also observed the existence of a protein with acetylcholinesterase activity at the
HUVECs membrane level confirmed by kinetic analysis, SDS-PAGE and Western blotting
analysis.
When acetylcholine was added to erythrocytes suspensions, NO basal levels measured by the
electrochemical method increased. This could be the result of a signal transduction mechanism
started by ACh binding to AChE that allow some internal globular displacement of some
reservoir NO molecules (S-nitrosohaemoglobin, nitrosothiols as S-nitrosoglutathione) to protein
band 3 translocation. The levels of NO compounds such as nitrite and nitrate also increased when
ACh is present in erythrocytes suspensions and this raised several interrogations in concurrent
chain reactions which is showed in the flow chart published in our work (J. Appl. Toxicol.22,
419-427; 2004). Our results still maintain the hypothesis for the possible AChE role in the signal
transduction mechanism in response to the action of ACh on nitrite and nitrate production. The
trans-nitrosylation process coupled between band 3 and SNOHb could be associated with an
unknown mechanism mediated by the AChE-ACh complex, with the participation of protein
tyrosine kinase dependent on G protein, and this must be tested.
We started a new experimental approach to study how AChE has non cholinergic action by
creating a method to induce erythrocyte membrane exovesicles production. Eventually a
pharmacological and cosmetic application could be developed, but our primary objective is to
inject in animal model to identify the endothelial cell signal expression
When NO donors such as SpermineNONOate is added to erythrocyte suspensions the

glyceraldehyde 3P dehydrogenase moves from protein band 3 and to the cytoplasm where at a
specific NO concentration increase its enzyme activity and the translocation seems to be
peroxinitrite concentration dependent. Inside the new paradigm that has attributed non cholinergic
functions to acetylcholine and also to the enzymes that promote it synthesis and hydrolysis an
emphasis is done to the anti-inflammatory role.
In 2000 our group observed that velnacrine maleate, an inhibitor of AChE, leads to an increase of
the number of adherent leukocytes to the endothelium of post-capillary venules of the mesentery
of Wistar rats in the presence of lipopolysaccaride (LPS). The systemic administration as well the
local application of velnacrine maleate leads to an increase of the number of leukocytes in rolling
in post-capillary venules of Wistar rat`s cremaster muscle without alteration of the adherent ones.
The local application of acetylcholine did not change the plasma levels of IL-1β at variance of
velnacrine that induce a significantly (p<0.0001) increase (double) of the interleukine 1β
concentration.
When human T lymphocytes suspensions are exposed to velnacrine maleate there is an increase
in the release of IL-1β which could be impaired by the addition to incubation medium of an
adenilate cyclase inhibitor. However acetylcholine has a similar effect as velnacrine maleate at
both the levels of AMPc and IL-1β. The understanding of the signal transduction pathway
involved and some “cross talk” are under study. Also the molecular characterization of T
lymphocyte AChE and its mRNA expression by RT-PCR are under experimental studies.
Carvalho, F.A., Martins-Silva, J., Saldanha, C. (2004) Amperometric measurements of nitric

oxide in erytrhocytes. Biosens. Bioelectron. 20:505-508. (Journal IF: 2.947)
Carvalho, F.A., Mesquita, R., Martins-Silva, J., Saldanha, C. (2004) Acetylcholine and choline
effects on erytrocytes nitrite and nitrate levels. J. Appl. Toxicol. 24:419-427. (Journal IF: 1.272)
Martin Martins, J., Vale, S., Trinca, A., Saldanha, C., Martins e Silva, J. (2004) Personality,
manual preference and neuroendocrine reactivity in hirsute subjects. Physiol. Behav. 82:741-749.
(Journal IF: 2.027)
Rosário, H.S., Waldo, S.W., Becker, S.A., Schmid-Schönbein, G.W. (2004) Pancreatic trypsin
increases matrix metalloproteinase-9 accumulation and activation during acute intestinal
ischemia-reperfusion in the rat. Am. J. Pathol. 164:1707-1716. (Journal IF: 6.946)
Saldanha, C., Santos, N.C., Martins e Silva, J. (2004) A colorimetric process to visualize
erythrocyte exovesicles aggregates. Biochem. Mol. Biol. Educ. 32:250-253. (Journal IF: 0.637)
Santos, N.C., Castanho, M.A.R.B. (2004) An overview of the biophysical applications of atomic
force microscopy. Biophys. Chem. 107:133-149. (Journal IF: 1.728)
Veiga, S., Henriques, S., Santos, N.C., Castanho, M. (2004) Putative role of membranes in the
HIV fusion inhibitor enfuvirtide mode of action at the molecular level. Biochem. J. 377:107-110.
(Journal IF: 4.101)
Veiga, A.S., Santos, N.C., Loura, L.M.S., Fedorov, A., Castanho, M.A.R.B. (2004) HIV Fusion
inhibitor peptide T-1249 is able to insert of absorb to lipidic bilayers. Putative correlation with
improved efficiency. J. Am. Chem. Soc. 126:14758-14763. (Journal IF: 6.516)
IMM – Immunology & Infectious Diseases Programme | 33
Immunology and Infectious Diseases Programme
Clinical Immunology Unit
The Clinical Immunology Unit is a translational research unit. The bench work is developed in
narrow interaction with the Department of Medicine 2 of the University Hospital of Santa Maria
(HSM), as well as with other hospital units where immunology has clinical impact.
Coordinator
Ana Espada de Sousa, MD, PhD – Researcher, FML
Research Team
Rui M.M. Victorino, M.D., Ph.D. – Professor of Medicine and Clinical Immunology, FML and
Director of the Department of Medicine 2, HSM
M. Conceição Santos, Pharm.D., Ph.D. – Researcher, FML
Carlos Ferreira, M.D., Ph.D. – Assistant Professor, FML, Consultant Physician, HSM
João Lacerda, M.D., Ph.D. – Assistant Professor, FML, Heamatologist, HSM
Vasco Maria, M.D., Ph.D. – Assistant Professor, FML
Miguel Garcia, Pharm.D., Ph.D. – Pos-Doc Fellow, Assistant Professor, ISCSS
Maria Soares, B.Sc., Ph.D. - Pos-Doc Fellowship, FCT (Since October 2004)
Russell B. Foxall, B.Sc., M.Sc. – PhD Fellowship, FCT
Rita Cavaleiro, B.Sc., M.Sc. – PhD Fellowship, FCT
Catarina Cortesão, B.Sc. – PhD Fellowship, FCT
Adriana Albuquerque, B.Sc. – Master student, FML, Research Fellowship, FCT
Rui Soares, B.Sc. – Master student, FML, Research Fellowship, GSK
Research Areas
HIV/AIDS Immunopathogenesis
HIV2 infection
Primary Immunodeficiencies
Immunological Reconstitution
Specific Immunotherapy
Immune-mediated Adverse Drug Reactions
Sousa, A.E., A.F. Chaves, M. Doroana, F. Antunes, and R.M. Victorino (1999) Kinetics of the
changes of lymphocyte subsets defined by cytokine production at single cell level during highly
active antiretroviral therapy for HIV-1 infection. Journal of Immunology 162:3718-26. (Times
cited: 34) (Journal IF: 7.014)
Cavaleiro, R., A.E. Sousa, A. Loureiro, and R.M. Victorino (2000) Marked immunosuppressive
effects of the HIV-2 envelope protein in spite of the lower HIV-2 pathogenicity. AIDS 14:2679-
86. (Times cited: 8) (Journal IF : 8.018)
Sousa, A.E., A.F. Chaves, A. Loureiro, and R.M. Victorino (2001) Comparison of the frequency
of interleukin (IL)-2-, interferon-gamma-, and IL-4-producing T cells in 2 diseases, human
immunodeficiency virus types 1 and 2, with distinct clinical outcomes. Journal of Infectious
Diseases 184:552-9. (Times cited: 7) (Journal IF : 4.910)
Grossman, Z., M. Meier-Schellersheim, A.E. Sousa, R.M. Victorino, and W.E. Paul (2002) CD4+
T-cell depletion in HIV infection: are we closer to understanding the cause? Nature Medicine
8:319-21. (Times cited: 83) (Journal IF : 28.740)
Sousa, A.E., J. Carneiro, M. Meier-Schellersheim, Z. Grossman, and R.M. Victorino (2002) CD4
T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2
but only indirectly to the viral load. Journal of Immunology 169:3400-06.
(Times cited: 37) (Journal IF:7.014)
2001/05 HIV2 infection as a model for the investigation of AIDS pathogenesis – PI: Rui
MM Victorino (FCT/POCTI 36312/CBO2000)
2001/04 Study of the frequency of antigen specific T cells in HIV1 and HIV2 infections:
Clinical correlations and effects of antiretroviral therapy – PI: Rui MM Victorino
(CNLCS/CRIA CR4639)
2003/05 Modulation of immune activation by HIV2 envelope proteins – PI: Ana E Sousa
(FCT/PSIDA/ESP/49655/2003)
2003/05 Lupus eritematoso sistémico: possível correlação de padrões clínicos,

psicológicos e espectro de aminas com função neural. M Alves, N Cortez-Dias,
Eugénia Santos, Manuel Bicho, Filipe Barbosa, António Barbosa, Carlos Ferreira
(GAPIC 13/2004).
The main focus of the research that is being conducted in our Laboratory is HIV/AIDS
pathogenesis through the study of a natural model of attenuated disease, the HIV2 infection.
Although CD4 T cells represent the main cell target of HIV, it is now clear that the direct
infection of this T cell subset does not explain its depletion. HIV induces strong specific immune
responses that limit its replication but are unable to achieve virus eradication. We and others have
shown that the virus persistency leads to a chronic generalized immune activation with functional
lymphocyte impairment that, in itself, contributes to the immunodeficiency. Many features of the
HIV/AIDS disease are a result of this delicate balance between the specific anti-HIV immune
response required for virus containment and the associated bystander immunopathology. New
immune-based therapeutic strategies can derive from the understanding of the mechanisms
involved in the regulation of this balance. Such strategies in conjunction with the use of highly
active antiretroviral therapy (HAART) could be decisive for the eradication of viral reservoirs
that are known to persist in spite of prolonged HAART. A better equilibrium with the host is
apparently established in HIV2 infection. There is no significant impact in the mortality rate of
the majority of HIV2 infected adults and HIV2 disease progression is much slower with lower
viremia than HIV1. The comparative study of these two immunodeficiencies can be instrumental
to clarify many central issues in AIDS pathogenesis. Portugal is the only non-African country
with a significant prevalence of HIV2 infection as a result of its close connections with Western
Africa where the HIV2 is endemic.
We have been characterizing anti-HIV2 helper and cytotoxic T cell responses with the aim of
understanding if the favourable outcome of HIV2 disease results from strong effective anti-viral
responses or is the consequence of the induction of viral tolerance. As a strategy to evaluate the
global HIV2 specific responses, we used the whole inactivated virus as a source of antigens. For
this purpose the HIV2 ROD and HIV1 MN whole viruses were chemically inactivated using
Aldrithiol-2 (AT2) that targets the Zinc atoms within the Zinc finger motifs of the nucleo-capside
viral protein rendering the virus inactive but still maintaining an intact envelope structure. Given
our previous experience with Intracellular Cytokine Staining (ICS) we have chosen it as the read-
out to determine the frequency and function of HIV specific CD4 and CD8 T cells in HIV2+ and
HIV1+ untreated patients that are currently being analysed.
Interleukin 7 (IL7) is thought to be a critical modulator of T cell homeostasis, able to restore

immune competence through a combination of increased thymic output and enhanced peripheral
expansion of T cells. Clinical studies have reported an increase in circulating levels of IL7 in the
settings of HIV1 induced T cell depletion, idiopathic CD4 lymphopenia or following cancer
chemotherapy, which were shown to return to normal levels upon recovery of the T cell
populations. A significant increase in circulating IL7 was noted in our HIV2 cohort, which
negatively correlated with CD4 counts and circulating naïve CD4 T cells. This correlation is
much stronger than the one observed for HIV1, both within our study and published data.
However, for a given degree of CD4 depletion, serum IL7 was no higher in the HIV2 cohort than
in the HIV1 infected patients. IL7 appears to be an important factor in T cell homeostasis in HIV2
disease, but our data suggest that the increased rate of CD4 loss in HIV1 infection seems to be
due to factors other than the IL7 mediated homeostatic response. Given the potential of IL7
therapy, the effects and detailed pathways of this cytokine on purified naïve, and on the different
memory-effector T cell subsets are currently being characterized in healthy and HIV infected
subjects. Moreover, we are pursuing the study of the role of the thymus through the measuring of
the T cell receptor (TCR) excision circles (TRECS), excision DNA generated during T cell
development that will allow us to get an indirect measurement of thymic output and through the
study of TCR repertoires.
HIV envelope (env) proteins have been shown to modulate several cellular functions apart from
infection. We have previously reported that HIV-2 env protein (gp105) has more marked
immunosuppressive properties than the corresponding env of HIV-1 and SIV (gp120), in spite of
the better prognosis of the HIV-2 disease. We have hypothesized that HIV-2 env suppressive
effects could limit the bursts of cellular activation, thus, reducing viremia and slowing
progression of disease. Now, we found that monocytes are the central mediators of HIV-2
envelope-induced T cell suppression through a cell contact dependent mechanism. Moreover, in
agreement with reports from some murine retroviruses, gp105 was shown to activate TLR4, in
contrast to gp120. Given the deleterious role of persistent immune activation on HIV/AIDS, these
findings identify a potential target for future immune intervention and suggest the possibility of
regions of HIV-2 env being used as immunomodulator tools.
In order to quantify the effective ongoing viral replication in HIV2 infected patients we
developed real time based quantitative PCR assays to measure the number of copies of DNA
provirus and viral mRNA. The ultimate objective is to understand why HIV2 infected patients
exhibit reduced plasmatic viral load in spite of having levels of proviral DNA (number of infected
cells) similar to the ones observed in HIV1 infected subjects. The data are currently being
analysed.
In 7 to 18% of HIV1 infected patients treated with HAART no immunological reconstitution was
achieved in spite of prolonged apparent suppression of the virus replication by the antiretroviral
drugs. A study is ongoing to characterize the mechanisms responsible for the absence of recovery
of CD4 counts in these patients.
CD25+ CD4+ regulatory T cells are now believed to be responsible for the regulation for a whole
range of immune responses. We have been characterizing this population in HIV1 and HIV2
persistent infections and the results indicate that it is apparently regulated independently of the
state of activation and CD4 depletion. CD25bright CD4+ regulatory T cells have also been
evaluated in the cohort of patients with Lupus Erythematosous Disseminated (LED) under study
in correlation with several clinical and laboratorial parameters. Furthermore, the study of their
role in specific immunotherapy for hymenopter venom allergy has also been started.
Our unit continues to provide clinical advice and immunological investigation in cases of
Immune-mediated Adverse Drug Reactions and in patients with primary imunodeficiencies. A
protocol has recently been established with the new pediatric unit of congenital
immunodefciencies at HSM. This meets the overall objective of making immunology expertise
available to patient care in frontline areas of clinical research.
Albuquerque, A., Maria, V., A., Loureiro, A., Sousa A., Victorino, R. (2004) Severe cholestatic
hepatitis induced by pyritinol. British Medical Journal 328:572-4. (Journal IF : 7.209)
Pinheiro, L., João Freitas, Margarida Lucas, Rui M.M. Victorino (2004) Cerebellar Atrophy in
Systemic Sclerosis. Journal of The Royal Society of Medicine 97:537-8. (Journal IF: 0.657)
Branco Ferreira, M., E. Pedro, J. Meneses Santos, M.C. Pereira Santos, M.L. Palma Carlos, B.
Bartolomé, A.G. Palma Carlos (2004) Latex and chickpea (Cicer arietinum) allergy: first
description of a new association. European Annals of Allergy and Clinical Immunology 36(10).
(Journal IF )
Barreto, M., Eugénia Santos, Ricardo Ferreira, Constantin Fesel, Francisca Fontes, Clara Pereira,
Berta Martins, Rita Andreia, João Faro Viana, Francisco Crespo, Carlos Vasconcelos, Carlos
Ferreira and Astrid Moura Vicente (2004) Evidence for CTLA4 as a susceptibility gene for
Systemic Lupus Erythematosus. European Journal of Genetics 12:620-6. (Journal IF: 3.669)
Gastroenterology Unit
Liver disease is an important cause of morbidity and mortality in the Portugal, affecting persons
of all ages, but most frequently individuals in the productive years of life, between the ages of 40
and 60 years. Medical research on liver disease is critically important and further progress in
research promises to bring under control the major toll of liver disease on human health and well-
being. Indeed, the last 25 years of medical research in liver disease has resulted in major
improvements in the survival and quality-of-life of patients with liver disease. The next 25 years
should bring even more profound and important changes.
The main objective of the Liver Unit is to investigate mechanisms involved in the progression of
liver injury in some of the more common liver diseases: hepatitis B and C viral infection, and
alcoholic and non-alcoholic steatohepatitis. Presently, the development of molecular technologies
with diagnostic and therapeutic application is still limited by the lack of basic knowledge
concerning the ways in which chronicity develops after the initial injury to the liver. Genetic and
non-genetic mechanisms may be important. The understanding of cellular and pathophysiologic
mechanisms in chronic hepatitis C and non-alcoholic steatohepatitis are the aim of several
research projects under way in our Clinical Unit at the Medical School and Hospital Santa Maria
in Lisbon.
Characterisation of neuroendocrine (NE) cells and tumours regarding their peptide content, NE
cell markers and somatostatin receptors; studies of autoimmunity to gastrointestinal NE cells; and
studies of endocrine pancreas in type-2 diabetes. In collaboration with the University of Uppsala,
Sweden.
Coordinator
Miguel Carneiro de Moura , MD, PhD – Full Professor, FML
Research Team
José Velosa, MD, PhD - Professor, FML

Rui Marinho, MD, PhD - Auxiliary Professor, FML
Fátima Serejo, M.D. PhD - Auxiliary Professor, FML
Luis Carrilho Ribeiro, MD, PhD - Auxiliary Professor, FML
Luis Costa, M.D.Ph.D, ( Oncology - )Auxiliary Professor, FML
Helena Cortez-Pinto, MD, PhD - Auxiliary Professor
Guida Portela Gomes, MD, PhD ( Pathology ) - Auxiliary Professor
Paula Alexandrino, MD - Gastrenterologist , HSM
Miguel Raimundo, MD - Gastroenterologist, HSM
Ana Valente, MD - Gastroenterologist , HSM
Rui Palma,MD - Gastroenterologist , HSM
Alexandra Martins, MD - Intern, Gastroenterologist, HSM
Carlos Ferreira, MD - Intern , Gastroenterologist, HSM
Cintia Sequeira - Auxiliary Investigator; FML
Research Areas
Fibrogenesis and oxidative stress in chronic hepatitis C

Non-alcoholic steatohepatitis – clinical and physiopathological aspects
Cellular immune responses in chronic hepatitis B and C
Models of artificial liver support
Liver metastasis; Genomics and proteomics of hepatocellular carcinoma.
NE cells of gastrointestinal tract. NE cells and markers in diabetes type 2.
Cortez-Pinto, H., Baptista, A., Camilo, M.E., Valente, A., Saragoça, A., Moura, M.C. (1996)
Nonalcoholic steatohepatitis: clinico-pathological comparison with alcoholic hepatitis in
ambulatory and hospitalized patients. Dig. Dis. Sci. 41:172-179.
(Times cited: 50) (Journal IF: 1.387 )
Fattovich, G. and the European Concerted Action on Hepatitis (EuroHep) (1997) Long-term
outcome of hepatitis B and antigen e-positive patients with compensated cirrhosis treated with
interferon alpha. Hepatology 26:1338-42. (Times cited: 67) (Journal IF )
Rodrigues, C.M.P., Brites, D., Serejo, F., Costa, A., Ramalho, F., Moura, M.C. (2000) Apoptotic
cell death does not parallel other indicators of liver damage in chronic hepatitis C patients. J.
Viral Hepatitis 7:175-183. (Times cited: 4) (Journal IF: 2.157)
Serejo, F., Costa, A., Oliveira, A.G., Ramalho, F., Batista, A., Moura, M.C. (2001) α-Interferon
improves liver fibrosis in chronic hepatitis C. Clinical significance of the serum n-terminal
propeptide of procollagen type III. Dig. Dis. Sci. 46:1684-1689.
(Times cited: 8) (Journal IF : 1.516)
Sousa, A.E., J. Carneiro, M. Meier-Schellersheim, Z. Grossman, and R.M. Victorino (2002) CD4
T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2
but only indirectly to the viral load. Journal of Immunology 169:3400-06.
(Times cited: 37) (Journal IF : 7.014)
2000/05 Study of the proliferative activity of hepatocytes and correlation with p53 in
patients with hepatocellular carcinoma. (Fundação da Ciência e Tecnologia)
2004/06 REPEAT STUDY (Roche MV17150). “A randomized, open-label, multicenter,

efficacy and safety examining the effects of duration of treatment and of a high
induction dose of Pegasys in combination with daily Copegus in patients with
chronic hepatitis C who did not respond to previous Peginterferon alfa-
2b/Ribavirin combination therapy”.
2004/06 Cytokines and bone matrix : importance in metastasis (Fundação da Ciência e

Tecnologia and grants from PenState University, Philadelphia)
2004/06 Study with DNA micro-arrays of liver metastasis of colon carcinoma (Fundação
da Ciência e Tecnologia and IMM)
2002/06 Pathophysiology of non-alcoholic steatohepatitis. Peripheral blood and liver

cytokines and correlation with parameters of hepatic injury ( degree of steatosis,
fibrosis, activation of stelate cells ) and the presence or absence of insulin
resistance (Fundação da Ciência e Tecnologia and grants from the Sociedade
Portuguesa de Gastrenterologia )
2004/06 Study of the expression of somatostatin receptors in benign and malignant

insulinomas (Fundação da Ciência e Tecnologia and grants from the University
of Uppsala)
2004/06 Studies of autoimmunity to gastrointestinal NE cells, regarding the identification

of possible autoantigens in inflammatory bowel disease. (Fundação da Ciência e
Tecnologia and grants from the University of Uppsala )
2004/07 Role of TGFβ1 polymorphism in the progression of fibrosis and its regression in
patients responders to antiviral therapy (Fundação da Ciência e Tecnologia and
other grants)
2005/06 Prospective study of abnormalities of ocular motility (discordant gaze) in patients

with non-alcoholic steatohepatitis.
2005/07 Prospective study of new non-invasive markers of fibrosis and liver “stiffness” as
studied by the FibroScan in patients with chronic hepatitis C and NASH
(Fundação da Ciência e Tecnologia , EASL)
Marinho, R., Pinto, R., Santos, M.L., Carneiro de Moura, M. (2004) Effects of interferon and
ribavirin combination therapy on CD4+ proliferation, lymphocyte activation and Th1 and Th2
cytokine profile in chronic hepatitis C. J. Viral Hepat. 11:206-16. (Journal IF: 3.258 )
Marinho, R., Pinto, R., Santos, M.L., Carneiro de Moura, M. (2004) Lymphocyte T helper
specific reactivity in sustained responders to interferon and ribavirin with negativation
(seroreversion) of anti-HCV. Liver Int. 24:413-8. (Journal IF -)
Tsolakis, T.V., Portela-Gomes, G.M. , Stridsberg, M., Grimelius, L. , et al. (2004) Malignant
gastric ghrelinoma with hyperghrelinemia. J. Clin. Endocrinol. Metab. 89:3739-3744. (Journal
IF: 5.873)
Portela-Gomes, G.M., Stridsberg, M., Grimelius, L., Falkmer, U.G., Falkmer, S. (2004)
Expression of chromogranins A, B, and C (secretogranin II), in human adrenal medulla and in
benign and malignant pheochromocytomas. An immunohistochemical study with region-specific
antibodies. APMIS 112:663-673. (Journal IF: 0.896)
Stridsberg, M., Janson, E.T., Portela-Gomes, G.M. (2004) Cellular localisation of chromogranins
and processed products in the diffuse neuroendocrine system and related tumours. Curr. Med.
Chem. Immunol. Endocrine Metab. Agents 4:149-160. (Journal IF: 4.409)
Portela-Gomes, G.M., Hacker, G.W., Weitgasser, R. (2004) Neuroendocrine cell markers for
pancreatic islets and tumors. Appl. Immunohistochem. Molec. Morphol. 12:183-192, 2004.
(Journal IF: 1.50)
Portela-Gomes, G.M., Grimelius, L., Stridsberg, M., Pelosi, G. (2004) The expression of synaptic
vesicle protein 2 (SV2) and sequences of the chromogranin A molecule in bronchial
neuroendocrine tumours of different degrees of differentiation. Regul. Pept. 122: 35.
(Journal IF: 2.235 )
Rheumatoid Arthritis Unit
The main objective of this Unit is to study the pathogenesis of Rheumatoid Arthritis (RA) in
order to characterize potential tools for the early diagnosis and prognosis and potential targets for
novel therapies. Investigations currently ongoing are devoted to the study of synovial tissue and
to the analysis of TNF-α polymorphisms as a diagnostic and prognostic factor in RA and as a
mean for the evaluation of treatment efficacy. This Unit is also involved in epidemiological
studies, in providing services to the community and in postgraduate teaching.
João Eurico Fonseca, MD, PhD – Auxiliary Professor, FML
Research Team
João Cavaleiro - PhD student

José Teles - MSc student
Helena Canhão, MD – Assistant, FML
Catarina Resende, MD – Assistant, FML
Luís Miranda, MD
Ana Filipa. Mourão, MD
Marta Sobral - MD
Research Areas
Rheumatoid Arthritis- epidemiology, early diagnosis, prognosis and pharmacogenetics.

TNF alpha polymorphisms- PCR and Sequencing.
Fonseca, J.E., H. Canhão, F.C. Dias, M.J. Leandro, C. Resende, J.C. Teixeira Costa, J.A. Pereira
Silva, M. Viana Queiroz (2000) Severity of rheumatoid arthritis in portuguese patients. Arthritis
& Rheumatism 43:470-1. (Times cited: 3) (Journal IF: 6.841)
Fonseca, J.E., H. Canhão, C. Resende, F. Saraiva, J.C. Teixeira Costa, J. Bravo Pimentão, M.
Carmo-Fonseca, J.A. Pereira da Silva, M. Viana de Queiroz (2000) Histology of the synovial
tissue: value of semiquantitative analysis for the prediction of joint erosion in rheumatoid
arthritis. Clinical and Experimental Rheumatology 18:559-64.
Fonseca, J.E., H. Canhão, F.C. Dias, M.J. Leandro, C. Resende, J.C. Teixeira Costa, J.A. Pereira
Silva, M. Viana Queiroz. (2001) Amyloidosis in a series of 964 portuguese rheumatoid arthritis
patients. Rheumatology 40:944-945. (Times cited: 0) (Journal IF:3.062)
Fonseca, J.E., Edwards, J.C., Blades, S., Goulding, N.J. (2002) Macrophage subpopulations in
rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich
microenvironments. Arthritis & Rheumatism 46:1210-6. (Times cited: 8) (Journal IF : 7.379)
Fonseca, J.E., Canhão, H., Teixeira da C.J., Pereira da S.J., Queiroz, M.V. (2002) Global
functional status in rheumatoid arthritis: disease duration and patient age. Clinical
Rheumatolology 21:32-4. (Times cited: 0) (Journal IF : 0.976)
2003/05 Tumor Necrosis Factor Gene and Rheumatoid Arthritis - Prognosis and
Pharmacogenetics (IMM/Schering-Plough Pharma)
Rheumatoid arthritis (RA) is a chronic inflammatory disease, affecting approximately 1% of the

population, with unknown aetiology, characterised by a preferential involvement of joint synovial
tissue (MacGregor, 1998). It can have a very aggressive course as can be inferred from the social
impact of the disease: after 10 years of evolution, over 50% of the patients are unable to work
(Yelin E and Callahan LF, 1995). Moreover, life expectancy is shorten by 10 years, due to the
disease itself and to an increased co-morbidity (Wolfe F et al, 1994).
In the last few years the management of RA has suffered a major revolution. In first place, a
better characterisation of the natural course of the disease allowed rheumatologists to understand
that very early in the disease major destructive events occur, leading to definitive damage. In
accordance to this, it became evident that an early aggressive treatment could in fact change the
functional outcome of the disease and even reduce mortality. Finally, the use of maximum
tolerated doses of methotrexate (MTX) and the introduction of tumour necrosis factor alpha
(TNF-α) antagonist therapy opened a new perspective to the RA treatment approach: at least for a
group of patients the ultimate goal became “disease remission”, not just “disease control”.
This optimistic view has some pitfalls. Currently RA is diagnosed on the basis of clinical
judgement, as no specific diagnostic tool is available. Although, based only on clinical data, early
diagnosis of RA can be difficult. This fact causes a significant delay in the initiation of effective
treatment and also postpones dose escalation of disease modifying drugs (DMARD). On the other
hand, RA is a heterogeneous disease and definitely an aggressive treatment is not essential for
every patient. In order to solve this problem, a core of clinical and laboratory features have been
suggested to be of prognostic relevance (such as high rheumatoid factor titre, high inflammatory
markers, low functional status, high number of involved joints, high number of macrophages in
synovial tissue) but, in fact, there are no consensual prognostic criteria. To make matters worse
the new biological approaches to RA management can be very effective in some patients, but in
others (approximately 20-30%) no clinical benefit can be depicted. In summary, some patients
with highly aggressive disease are being lately identified, whether others are being unnecessarily
exposed to the risk of adverse effects and contributing to a decrease of treatment cost-
effectiveness.
Having considered these arguments, it would be of great value the development of diagnostic and
prognostic tools for RA. In addition, the development of a test capable of identifying the patients
who would most benefit from TNF-α antagonist therapy could have also a major impact on RA
management.
Given the importance of cytokines in RA physiopathology and the major effect of TNF-α
antagonist therapy on the clinical and laboratory manifestations of this disease it is plausible that
some cytokine genotypes might be relevant to the susceptibility to the disease, prognosis and
pharmacogenetics. One of the most promising candidate genes is the TNF gene, located in the
MHC locus on chromosome 6. The data available so far supports a possible role for the TNF gene
at least in the prognosis of RA and its pharmacogenetic relevance is highly plausible and should
be actively sought.
Pereira Silva, J.A., F. Costa Dias, J.E. Fonseca, H. Canhão, C. Resende., M. Viana Queiroz
(2004) Low bone mineral density in professional scuba divers. Clinical Rheumatololy 23:19-20.
(Journal IF : 0.850)
Viral Pathogenesis Unit
The overall aim is to gain an understanding of basic molecular mechanisms afforded by

herpesviruses. Our motivation is that this approach will increase our understanding of viral
pathogenesis and also reveal potential strategies for therapeutic intervention.The model system
consists of infection of laboratory mice with MHV-68 that establishes latent infection in B cells.
Using this model we have recently identified and characterized viral proteins with
immunomodulatory functions. Presently we are focusing our efforts in two ORFs designated M2
and ORF73. We have confirmed that both ORFs are important for the establishment of latenc,
and thus have initiated studies to reveal the role that these proteins play during in vivo infection.
We have shown that M2 modulates B cell receptor induced antigen triggered activation, and that
ORF73 modulates NF-kB transcriptional activity.
João Pedro Simas, DVM, PhD – Assistant Professor, FML
Research Team
Marta Miranda - Post-Doc Fellow, FCT

Patricia Madureira – PhD Fellowship, FCT/FML
Sofia Marques – PhD Fellowship, FCT/FML
Lenia Rodrigues – PhD Fellowship, FCT/FML
Rui Freitas – PhD Fellowship, FCT/FML
Sofia Corte Real – PhD Fellowship, FCT/FML
Lidia Fonseca – Technitian, EU
Research Areas
Viral Pathogenesis
BSE and Scrapie
Bridgeman, A., Stevenson, P., Simas, J.P., Efstathiou, S. (2001) A secreted chemokine binding
protein encoded by murine gammaherpesvirus 68 is necessary for the establishment of a normal
latent load. Journal of Experimental Medicine 194:1-13. (Times cited: 36) (Journal IF: 15.340)
Stevenson, P.G., J. S. May, X. G. Smith, S. Marques, H. Adler, U. H. Koszinowski, J. P. Simas,

and S. Efstathiou (2002) CD8+ T cell evasion by K3 plays a critical role in the amplification of a
latent γ-herpesvirus. Nature Immunology 3:733-40. (Times cited: 21) (Journal IF: 27.868)
Fowler, P., Sofia Marques, J. Pedro Simas and Stacey Efstathiou (2003) ORF73 of murine
herpesvirus-68 is critical for the establishment and maintenance of latency. Journal of General
Virology 84:3405-3416. (Times cited: 4) (Journal IF: 3.036)
Marques, S., Stacey Efstathiou, Kenneth G. C. Smith, Matthias Haury and J. Pedro Simas (2003)
Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes. Journal of
Virology 77:7308-7318. (Times cited: 9) (Journal IF: 5.225)
Simas, J.P., Sofia Marques, Anne Bridgeman, Stacey Efstathiou, and Heiko Alder (2004) The M2
gene product of MHV-68 is required for efficient colonisation of splenic follicles but not
necessary for expansion of latently infected GC B cells. Journal of General Virology 85(Pt
10):2789-97. (Times cited: 1) (Journal IF: 3.036)
1. Project Title:
“Molecular interactions in Murine Herpesvirus 68 Latent Infection of B-Lymphocytes”

(SAPIENS/34240/99)
Members (PI and Pos-Docs):
Pedro Simas (PI)
Marta Miranda (Pos-Doc; FCT)
Students and Technicians:

Patricia Madureira (PhD; FCT/FML)
Sofia Marques (PhD; FCT/FML)
Lenia Rodrigues (PhD; FCT/FML)
External Collaborators (name and origin):

Stacey Eftstathiou (University of Cambridge, UK)
Project Description:
Studies into the molecular basis of gammaherpesvirus latency have been hindered by the lack of
amenable animal model systems and the lack of fully permissive cell lines, which are required for
the genetic manipulation of these viruses. This project centres on the utilisation of a
gammaherpesvirus, designated murine herpesvirus 68 (MHV-68), whose pathogenesis can be
readily investigated in the laboratory mouse (for recent reviews see Simas & Efstathiou, 1998;
Virgin VI & Speck, 1999). MHV-68 is genetically related to Epstein-Barr virus and Kaposi’s
sarcoma associated herpesvirus, which are important Human pathogens. Experimental infection
of inbred strains of mice with MHV-68 results in acute productive infection of the lung followed
by latent infection of B-lymphocytes and macrophages. Comparison of the genomic organisation
of MHV-68 with other gammaherpesviruses shows that they have large blocks of co-linearly
arranged conserved genes, interspersed with virus specific ORFs and a number of cellular
homologues, which are predicted to determine the particular biological properties of these
viruses, e.g. host range, immune evasion, latency and disease. MHV-68 has 14 unique such
genes, designated M1 to M14, and a number of cellular homologues, including a complement
control protein, a D-type cyclin and an IL8 receptor. In addition to these cellular homologues two
of the ‘M’ genes, M1 and M11, show low level similarity to serpins and bcl2 cellular proteins,
respectively.
Our research interests are focused in trying to understand how these cellular homologues and
unique ORFs coordinate their functions with those of a B-lymphocyte and result in immune
evasion and persistent infection. Recente studies have identified selective transcription of a
number of viral genes during latent infection in spleen, including M2, M3 and M9 (Simas et al.,
1999; Virgin et al., 1999; Hussain et al., 1999). We have recently shown that the M3 gene,
encodes a secreted chemokine binding protein (Parry et al., 2000). As yet no function has been
allocated to either M2 or M9 and both of these ORFs do not show significant homology to any
known proteins.
The proposed project aims to elucidate the function of these two ORFs, M2 and M9, by
determining their respective cellular molecular targets and analysing the biology of deletion
mutant viruses. The procedure chosen will use, in parallel, the Yeast Two-Hybrid System and
MALDI peptide mass mapping combined with sequence database searching, to identify cellular
molecular targets for these proteins. Once interacting cellular proteins have been identified it
may be possible to predict and test for function, in vivo, by constructing MHV-68 recombinants
with either deleted or modified M2 or M9 genes. This approach should give valuable insights into
general mechanisms by which gammaherpesviruses evade immune responses and establish
persistent/latent infections in the host.
2. Project Title:
“Antiviral peptides blocking herpes simplex virus type 1 entry into cells”
(EU-QLK2-CT-2002-00810)

Pedro Simas (PI)
Marta Miranda (Pos-Doc)

Lidia Fonseca (Technitian)

Massimiliano Galdiero (University of Napoli, Italy)
Human herpes simplex virus 1 (HSV-1) affects over 50% of the European Union adult
population. No vaccines, despite repeated attempts, are yet available for prevention, but classical
antivirals such as nucleosides are the choice chemotherapies. Nevertheless, HSV resistant strains
and the failure to completely relieve symptoms (especially in immunocompromised individuals)
make it imperative that antivirals that utilize new mechanisms of action are developed and
marketed.
This project will develop a new class of anti-HSV-1 drugs – peptides that act at the cell surface
blocking virus entry. Peptides will be designed and tested to several HSV glycoproteins, namely
gB, gD, gH and gL, which are all involved in virus attachment and penetration. Because such
peptides will function via an extracellular novel mechanism they should prove complementary,
not competitive, with current antiviral chemotherapies; predictably combined therapy, as with
anti-HIV therapies, may prove the most common use of antiviral peptides that block virus entry.
3. Project Title:
“Transcriptome analysis of germinal centre B cells during gammaherpesvirus latent infection”

(POCTI/ESP/46378/02)

Pedro Simas (PI)

Sofia Marques (PhD-student)
Rui Freitas (PhD-student)

Paul Lyons and Sytacey Efstathiou (University of Cambridge)
Analysis of genomes from gammaherpesviruses reveals the presence of large blocks of co-
linearly arranged conserved genes interspersed with virus specific ORFs and cellular homologues.
Hence, there are two classes of putative viral host control proteins, namely those encoded by
genes with and without sequence similarity to cellular genes. The existence of viral homologues
to cellular genes suggests that during co-evolution viruses have ‘hijacked’ host genes that were
subsequently modified for the benefit of the virus. Virus specific ORFs may represent novel
structures with functional activities homologous to cellular proteins or could simply be an
example of proteins for which the host homologues have not yet been identified.
Our objectives are focused in trying to reveal the molecular function that these ORFs and cellular
homologues have in a context of infection, that result in evasion of the host immune response and
life-long latency. To this end we use a gammaherpesvirus designated murine herpesvirus 68, as
its pathogenesis can investigated in the laboratory mice.
This project investigates the effect that MHV68 latent infection has upon GC B cell physiology
by analyzing their transcription profile. We propose to use a strategy involving transgenic mice
with a floxed EGFP allele that only becomes functional upon Cre mediated excision. In this
model, Cre will be provided by a recombinant MHV68 resulting in the fluorescent tagging of
latently infected cells. This makes possible the purification of pure populations of latently
infected GC B cells, a pre-requisite for DNA microarray analysis.
It is hoped that this strategy will identify key cellular genes and biochemical pathways tha are
involved in cellular functions important for the control of gammaherpesvirus infection.
Knowledge gained from this type of approach may not only help determining the molecular basis
for gammaherpesvirus infection but also provide clues on what gene products (either cellular or
viral) may have therapeutic uses themselves or may be targets for therapeutic intervention.
4. Project Title:
“Modulation of NF-kB transcriptional activity during gamma-herpesvirus infection”

(POCTI /BIA/BCM/60670/04)

Pedro Simas (PI)
Sofia Marques (PhD)

Lidia Fonseca
Analysis of genomes from gammaherpesviruses reveals the presence of large blocks of co-
linearly arranged conserved genes interspersed with virus specific ORFs and cellular homologues.
Hence, there are two classes of putative viral host control proteins, namely those encoded by
genes with and without sequence similarity to cellular genes. The existence of viral homologues
to cellular genes suggests that during co-evolution viruses have ‘hijacked’ host genes that were
subsequently modified for the benefit of the virus. Virus specific ORFs may represent novel
structures with functional activities homologous to cellular proteins or could simply be an
example of proteins for which the host homologues have not yet been identified.
Our objectives are focused in trying to reveal the molecular function that these ORFs and cellular
homologues have in a context of infection, that result in evasion of the host immune response and
life-long latency. To this end we use a gammaherpesvirus designated murine herpesvirus 68, as
its pathogenesis can investigated in the laboratory mice.
This project investigates the effect that MHV68 latent infection has upon GC B cell physiology
by analyzing their transcription profile. We propose to use a strategy involving transgenic mice
with a floxed EGFP allele that only becomes functional upon Cre mediated excision. In this
model, Cre will be provided by a recombinant MHV68 resulting in the fluorescent tagging of
latently infected cells. This makes possible the purification of pure populations of latently
infected GC B cells, a pre-requisite for DNA microarray analysis.
It is hoped that this strategy will identify key cellular genes and biochemical pathways tha are
involved in cellular functions important for the control of gammaherpesvirus infection.
Knowledge gained from this type of approach may not only help determining the molecular basis
for gammaherpesvirus infection but also provide clues on what gene products (either cellular or
viral) may have therapeutic uses themselves or may be targets for therapeutic intervention
Orge, L., Alexandre Galo, Carla Lima, Cristina Ochoa, João Silva, Manuel Ramos and J. Pedro
Simas (2004) Identification of putative atypical scrapie in sheep in Portugal. Journal of General
Virology 85(Pt 11):3487-91. (Journal IF: 3.036)
Simas, J.P., Sofia Marques, Anne Bridgeman, Stacey Efstathiou, and Heiko Alder (2004) The M2
gene product of MHV-68 is required for efficient colonisation of splenic follicles but not
necessary for expansion of latently infected GC B cells. Journal of General Virology 85(Pt
10):2789-97. (Journal IF: 3.036 )
Molecular Microbiology and Infection Unit
The main objective of the Molecular Microbiology and Infection Unit is to understand the
dynamics of populations of bacterial pathogens and how they respond to selective forces. Current
work focuses on characterizing the effect of antimicrobial use and human vaccination on the
bacterial population. Investigations are also exploring the relationships between commensal and
disease causing populations of the same bacterial pathogen with the aim of identifying
particularly successful clones at causing disease as well as successful colonizers for further
characterization. The development of novel laboratory methodologies for the diagnostic of
infectious diseases is also an active area of research.
Mário Ramirez, PhD – Assistant professor, FML
Research Team
José Melo Cristino, MD, PhD – Full Professor, FML

Thomas Hänscheid, MD, PhD - Assistant Professor, FML
Isa Serrano - PhD Fellowship, FCT
Sandra Aguiar - Fellowship, UE
Maria João Frias - Fellowship, UE
Elisabete Martins - Fellowship, FCT
Marcos Pinho - Fellowship, FCT
Teresa Figueiredo - Fellowship, FCT
Research Areas
Molecular epidemiology
Bacteriophage genomics
Antimicrobial resistance mechanisms
Novel diagnostic tools
Ramirez, M., Severina, E., Tomasz, A. (1999) A high incidence of prophage carriage among
natural isolates of Streptococcus pneumoniae. Journal of Bacteriology 181:3618-3625.
Melo-Cristino, J. (1999) Correlation between consumption of antimicrobials in humans and

development of resistance in bacteria. International Journal of Antimicrobial Agents 12: 199-202.
Alou, L., Ramirez, M., Garcia-Rey, C., Prieto, J., de Lencastre, H. (2001) Streptococcus
pneumoniae isolates with reduced susceptibility to ciprofloxacin in Spain: Clonal diversity and
appearance of ciprofloxacin-resistant epidemic clones. Antimicrobial Agents and Chemotherapy
Melo-Cristino, J., Fernandes, M.L., Serrano, N., The Portuguese Surveillance Group for the Study
of Respiratory Pathogens (2001) A multicenter study of the antimicrobial susceptibility of
Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis isolated from
patients with community-acquired lower respiratory tract infections in 1999 in Portugal.
Microbial Drug Resistance 7:33-38. (Times cited: 8) (Journal IF: 2.60)
Hanscheid, T., Grobusch, M.P. (2002) How useful is PCR in the diagnosis of malaria? Trends in
Parasitology 18:395-398. (Times cited: 10) (Journal IF: 5.375)
2001/04 Characterization of bacteriophage impact and dynamics in natural populations of

Streptococcus pneumoniae. Fundação para a Ciência e a Tecnologia (FCT-BME
34418/99).
2001/04 Molecular epidemiology, prevention and therapy of S. pneumoniae invasive

infections in Portugal. Fundação Calouste Gulbenkian.
2002/05 Epidemiologic and molecular study of Streptococcus haemolyticus infections in

Portugal. Fundação Calouste Gulbenkian.
2003/05 Desenvolvimento e avaliação de um novo método rápido para o diagnóstico e

teste de sensibilidade de M. tuberculosis em doentes com infecção VIH.
(PSIDA/ESP/49722/03)
2004/06 Pneumococcal phase transition between colonization and disease . Fundação para
a Ciência e a Tecnologia (POCTI/ESP/47914/2002)
2004/06 PREVIS: Pneumococcal Resistance Epidemicity and Virulence – an International

Study (FP6-2002-CT-503413)
Antimicrobial resistance of pathogens belonging to the genus Streptococcus: The

investigations on this field have benefited from a close contact with clinical practice and have
focused on issues directly relevant to the clinician. Special attention has been given to the
epidemiology of antimicrobial resistance at a national level. These data are essential for the
preparation of guidelines for empirical therapy as well as for an understanding of the evolution
and dissemination of antimicrobial resistance. The evaluation of the in vitro activity of new
antimicrobial agents against clinical isolates and the investigation on the possibility of using
bacteriophages as alternative prophylactic or therapeutic agents both stem from our interest in
new therapeutic approaches.
The use of molecular technologies will provide further detail to these analyses by allowing the
molecular identification of bacterial clones and their association to known resistance
determinants. This will afford new insights into the 1) clonality of clinical isolates; 2) the
distribution of antimicrobial resistance determinants and 3) the dispersal of clones. The later
information will be particularly useful at the health-care center level were outbreak detection can
be the basis for the implementation of containment measures. A more fundamental development
will be the identification of clones with high epidemicity or particularly virulent for future
analyses.
New diagnosis of parasitic diseases: The immediate developments in this line of research will
follow the recent realization that flow cytometric principles allow the detection of malaria
pigment. This finding will be further explored with the development of this application to the
diagnosis of malaria and the development of a novel sensitivity test. This method will also be
investigated for it’s usefullness as markers of disease severity. Furthermore, this research will be
used to address questions on the interactions of hemozoin and its effect on the immune system.
Finally, the results of this research may be useful for the understanding and development of novel
antimalarial drugs, because hemozoin seems to be the target of several of the most effective
antimalarials available today.
Development of flow cytometry based viability tests for mycobacteria: Research in this area
tries to improve and optimize methods to assess the viability of bacteria using specific
fluorochromes detected by flow cytometry. One aim of these investigations is the development of
a rapid sensitivity test for Mycobacterium spp. that provides clinically useful results within 2-4
days after obtaining a positive culture.
Investigation of novel diagnostic methods for tuberculosis: Cultural confirmation of

tuberculosis can take up to 8 weeks, a delay which is associated with many difficulties and
problems in clinical management and in public health. Research in this area tries to establish and
assess novel diagnostic methods. One area is the investigation of the usefulness of blood cultures
for the detection of Mycobacterium tuberculosis, while another approach is the detection of
specific cytokine secreting T-cells after stimulation with antigens that are only produced by
replicating Mycobacterium tuberculosis.
Evolution and population biology of bacterial pathogens: Lack of knowledge on the dynamics
of pathogenic bacteria population structure and the forces shaping it motivates our research in this
area. We are interested in the role of chromosome plasticity in bacterial adaptation, with a special
emphasis in gene exchange and mobile genetic elements.
Current efforts in the characterization of the bacteriophage (phage) population of Streptococcus

pneumoniae addresses the role of phages as bacterial “predators” and their potential influence in
the bacterial population structure. Simultaneously, their role in bacterial pathogenesis is
investigated by testing for the presence of virulence enhancing traits in phage genomes. Another
project is focusing on the response of the population of disease causing bacteria to another major
selective pressure, i.e., the introduction of a vaccine. Underlying these questions is the
fundamental issue of the relationship between colonizing isolates and the ones causing disease.
Taking advantage of the detailed information available on colonization isolates in Portugal we are
addressing this question by characterizing contemporary disease causing isolates and exploring
the relationships between these two populations. The availability of novel genomic technologies
will allow future work to survey the gene complement of these two populations and the relative
distribution of mobile genetic elements among them. We expect that the use of these technologies
will also open new lines of research on the bacterial adaptation to the expression of acquired
genes, of particular interest is the change in virulence caused by gene acquisition.
Conceição, T., N. Faria, L. Lito, J. Melo Cristino, M. J. Salgado, and A. Duarte (2004) Diversity
of chromosomal AmpC beta-lactamases from Enterobacter cloacae isolates in a Portuguese
hospital. FEMS Microbiol Lett 230:197-202. (Journal IF: 1.932)
Conceição, T., N. Faria, M. Pimentel, G. Soveral, A. Duarte, L. M. Lito, J. Melo Cristino, and M.
J. Salgado (2004) New chromosomal AmpC beta-lactamase in Enterobacter cloacae. Antimicrob
Agents Chemother. 48:1437. (Journal IF: 4.246 )
Figueira-Coelho, J., M. Ramirez, M.J. Salgado, and J. Melo-Cristino (2004) Streptococcus

agalactiae in a large Portuguese teaching hospital: antimicrobial susceptibility, serotype
distribution, and clonal analysis of macrolide-resistant isolates. Microb. Drug Resist. 10:31-36.
Hänscheid, T., C. Monteiro, L. Marques-Lito, J. Melo-Cristino, and M.J. Salgado (2004)

Usefulness of Myco/F Lytic blood cultures (Bactec 9050) in the detection of Mycobacterium
tuberculosis bacteraemia in HIV-infected patients in Portugal. Int. J. Infect. Dis. 8:253-254.ä
(Journal IF: 4.481)
Serrano, I., M. Ramirez, The Portuguese Surveillance Group for the Study of Respiratory
Pathogens, and J. Melo-Cristino (2004) Invasive Streptococcus pneumoniae from Portugal:
implications for vaccination and antimicrobial therapy. Clin. Microbiol. Infect. 10:652-656.
(Journal IF: 2.238)
Valadas, E., T. Hänscheid, and F. Antunes (2004) HIV Infection and non-tuberculous
mycobacteria: how important in southern European countries? Scand. J. Infect. Dis. 36:685-686.
Zé-Zé, L., R. Tenreiro, A. Duarte, M.J. Salgado, J. Melo-Cristino, L. Lito, M. M. Carmo, S.

Felisberto, and G. Carmo (2004) Case of aortic endocarditis caused by Lactobacillus casei. J.
Med. Microbiol. 53:451-453. (Journal IF : 1.987 )
IMM – Neurosciences Programme | 53
Neurosciences Programme
Neurosciences and Pathophysiology Unit
Coordinator
Joaquim Alexandre Ribeiro, MD, PhD – Full Professor, FML
Neurosciences Laboratory
Neuromodulation Group – Principal Investigator:

Joaquim Alexandre Ribeiro, MD, PhD – Full Professor, FML
The research performed by this group aims the elucidation of fine tune regulation of the chemical
synapses by neuromodulators (e.g. purines, neuropeptides). Electrophisiological and
neurochemical techniques are used to recognize the way neurotransmitters are controlled at the
synaptic level and the implications of this knowledge in brain dysfunctions.
Research Team
Luisa V. Lopes - PhD Fellowship, FCT

Marta Moita, Ph.D - Post-Doc Fellowship, FCT
Isabel Maria Fragata, MD, Ms D - Assistant, FML
Nuno Canas, MD, Ms D - Assistant, FML
António Pinto Duarte, Ms D - PhD Student
Catarina Gomes, Ms D - PhD Fellowship, FCT
Nuno Félix – Master Degree Student
António Francisco – Master Degree Student
Inês Pereira – Undergraduate Degree Thesis
M Helena Sequeira - Technician
Rodrigo Cunha, PhD - Visiting Scientist
Research Areas
Neurosecretion
Genesis of Neuromodulators
Neuro-Modulation: a need to communicate between synapses and/or a way to protect neurons
from insults.
Cunha, J.A., Sebastião, A.M. & Ribeiro, J. A. (1998). Inhibition by ATP of hippocampal synaptic
transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and
channeling to adenosine A1 receptors J. Neurosci., 18, 1987-1995.
(Times cited: 77) (Journal IF: 8.306).
Ribeiro, J.A. (1999). Adenosine A2A receptor interactions with receptors for other
neurotransmitters and neuromodulators. Eur. J. Pharmacol., 375, 101-113.
de Mendonça, A., Sebastião, A.M. & Ribeiro, J. A. (2000) Adenosine- does it have a
neuroprotective role after all? Brain Res. Rev., 33, 258-274.
Sebastião, A.M. & Ribeiro, J.A. (2000) Fine tuning neuromodulation by adenosine Trends
Pharmacol. Sci., 21, 341-346. (Times cited: 61) (Journal IF: 13.965).
Ribeiro, J.A, Sebastião, A.M. De Mendonça, A., (2003). Adenosine receptors in the nervous
system: pathophysiological implications. Prog. Neurobiol. 68, 377-392.
1998/2006 Adenosine transport – adenosine receptor interactions (International Brain

Research Organization (IBRO)).
2001/04 Role of adenosine in neurotransmitter release (FCT, Sapiens 99).
2001/05 Purines and control of astrocyte-neuronal signalling in rat hippocampal slices and
cell cultures (POCTI/43634/99)
2001/05 Purines and the central nervous system control of autonomic function
(POCTI/37332/FCB/2001)
The main objective of the research of the above projects is to understand how adenosine, an
ubiquitous homeostatic substance released through specific bi-directional transporters from most
cells, including neurones and glia, once in the extracellular space affects neuronal and glial
functioning. The type of G-protein-adenosine coupled receptors (GPCR: A(1) (high affinity),
A(2A) (high affinity), A(2B) (low affinity), A(3) (low affinity)) that can inhibit (A(1)) or enhance
(A(2A)) neuronal communication and/or neuron-astrocyte interactions are matter of on going
investigation. How interactions between these high affinity adenosine receptors and other G-
protein-coupled receptors can occur, and how it might contribute to a fine-tuning for neuronal
functioning is presently under investigation in hippocampal slices and in models of nerve
terminals (synaptosomes). Understanding the role of this nucleoside as a ‘fine tuner’ of the brain,
one could predict how manipulations of adenosine receptors, with agonists or antagonists, can
influence sleep and arousal, cognition and memory, neuronal damage and degeneration, as well as
neuronal maturation. These actions might have therapeutic implications for neurodegenerative
diseases such as Parkinson's disease, Alzheimer's disease, as well as for other neurological
situations such as epilepsy, idiopathic pain or even drug addition. As we consider adenosine as a
fine-tuning modulator involved in neuroprotection, then to study their subtle effects, which
promote the harmonization of the neurotransmitter actions in their neuronal activity, will reveal to
be an important approach to understand some of the mechanisms involved in brain dysfunctions.
So, our studies imply that whenever adenosine homeostasis is disrupted, pathology may be
installed and selective adenosine receptor antagonism or agonism required.
Canas, N., Pereira, I.T., Ribeiro, J.A. & Sebastião, A.M. (2004) Brain-derived neurotrophic
factor facilitates glutamate and inhibits GABA release from hippocampal synaptosomes through
different mechanisms. Brain Res. 1016:72-78. (Journal IF: 2.474) *
Cunha, R.A., Ribeiro, J.A. & Malva, J.O. (2004) Presynaptic kainate receptors modulating
glutamatergic transmission in the rat hippocampus are inhibited by arachidonic acid. Neurochem.
Int. 44:371-379. (Journal IF: 3.261)
Cunha-Reis, D., Sebastião, A.M. Wirkner, K. Illes, P. & Ribeiro, J.A. (2004) VIP enhances both
pre- and postsynaptic GABAergic transmission to hippocampal interneurones leading to
increased excitatory synaptic transmission to CA1 pyramidal cells. Br. J. Pharmacol. 143:733-
744. (Journal IF: 3.611) *
Diógenes, M.J., Fernandes, C.C., Sebastião, A.M. & Ribeiro, J.A. (2004) Activation of adenosine
A2A receptor facilitates BDNF modulation of synaptic transmission in hippocampal slices. J.
Neurosci. 24:2905-2913. (Journal IF: 8.306) *
Halldner, L., Lopes, L.V., Dare, E., Lindstrom, K., Johansson, B., Ledent, C., Cunha, R.A.,
Fredholm, B.B. (2004) Binding of adenosine receptor ligands to brain of adenosine receptor
knock-out mice: evidence that CGS 21680 binds to A(1) receptors in hippocampus. Naunyn
Schmiedebergs Arch. Pharmacol. 370:270-278. (Journal IF: 2.101)
Illes, P. & Ribeiro, J.A. (2004) Neuronal P2 receptors of the central nervous system. Cur. Topics
Med. Chem. 4:831-838. (Journal IF: 4.409)
Illes, P. & Ribeiro, J.A. (2004) Molecular physiology of P2 receptors in the central nervous
system. Eur. J. Pharmacol. 483 :5-17. (Journal IF: 2.352)
Lopes, L.V., Halldner, L., Rebola, N., Johsnsson, B., Ledent, C., Fan Chen, J., Fredholm, B.B.,
and Cunha, R.A. (2004) Binding of prototypical adenosine A2A receptor agonist CGS 21680 to
the cerebral cortex of adenosine A1 and A2 receptor knockout mice. Br. J. Pharmacol. 141:1006-
1014. (Journal IF: 3.611)
* These papers are also listed as publications from A. M. Sebastião

Neuroprotection Group – Principal Investigator:

Ana M. Sebastião, PhD – Associate Professor, FML
The main objective of the Neuroprotection group is to investigate mechanisms involved in

neuronal protection. When neuronal cells suffer an insult (e.g. hypoxia) they release substances,
some of them being involved in regulation of the activity and neuroprotection. One of these
substances is adenosine that besides acting itself as a neuroprotective agent, interacts with other
substances (e.g. neurotrophins), also relevant for cell survival. Our aim is to evaluate the interplay
between different neuroprotective substances and therefore to contribute for the understanding of
how neurones can be helped to survive and recover from insults.
Research Team
Diana Cunha-Reis, PhD - Fellowship, FCT

Maria José Diogenes, PhD - Fellowship, FCT
Catarina Fernandes, PhD - Fellowship, FCT
Natália Lopes, Ms D. - PhD Student
José Artur Lourenço – Master’s Degree Student
Amilcar Silva dos Santos – Master’s Degree Student
Paula Luís – Master’s Degree Student
João Fonseca – Master’s Degree Student
Susana Barahona – Master’s Degree Student
Sandra Vaz – Undergraduate Degree thesis
Elvira Duarte - Technician
José Francisco Cascalheira, PhD - UBI, Visiting Scientist
Research Areas
How neurons recover from insults

Synaptic transmission during insults
Adenosine, Neurotrophic factors and neuroprotection
Cunha, J.A., Sebastião, A.M. & Ribeiro, J.A. (1998) Inhibition by ATP of hippocampal synaptic
transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and
channeling to adenosine A1 receptors J. Neurosci. 18:1987-1995.
Sebastião, A.M. & Ribeiro, J.A. (2000) Fine tuning neuromodulation by adenosine. Trends
Pharmacol. Sci. 21:341-346. (Times cited: 61) (Journal IF: 13.965).
Sebastião, A.M., De Mendonça, A., Moreira, T. & Ribeiro, J.A. (2001) Activation of synaptic
NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs
recovery of synaptic transmission upon reoxygenation. J. Neurosci. 21:8564-8571.
Ribeiro, J.A., Sebastião, A.M., De Mendonça, A., (2003) Adenosine receptors in the nervous
system: pathophysiological implications. Prog. Neurobiol. 68:377-392.
Neurosci. 24:2905-2913. (Times cited: 3) (Journal IF: 8.306)
2003/06 ‘Modulation of synaptic transmission in interneurones: Role of adenosine”.

Fundação para a Ciência e a tecnologia (POCTI/37398/NSE/2001)
2004/05 Scientific collaboration project with Knut Biber, University of Groningen to

evaluate interplay between adenosine and interleukin-6, a neuroprotective agent
released by glial cells.
2004/06 Research Collaboration Agreement with Regeneron Pharmaceuticals Inc. They

supply, free of charge and under demand, Brain Derived Neurotrophic Factor
(BDNF) for our studies on the synaptic actions of BDNF in the hippocampus and
its interplay with adenosine.
2005/08 ‘Neurotrophins and neuronal communication: fine tuning by adenosine”.

Fundação para a Ciência e a Tecnologia (POCTI/SAU/56332/2004)
We recently found that adenosine, through A2A receptors, facilitates actions of neurotrophins. A
main objective of one of the ongoing projects is to further investigate the molecular mechanisms
involved in the interaction between BDNF and adenosine in the hippocampus. We already know
that pre-synaptic release of adenosine evoked either by high-frequency stimulation or by
depolarization, with subsequent pre-synaptic enhancement in cyclic AMP levels and activation of
its substrate, protein kinase A (PKA), are involved in the triggering of synaptic actions of BDNF.
We now want to identify the targets of these adenosine A2A receptors/cyclic AMP-mediated
events. Another objective is to identify if the observed interaction between adenosine A2A
receptors and trkB receptors is also extended to other actions of BDNF in neurones and glia.
Attention will be paid to the actions of BDNF in synaptic plasticity and in glutamate and GABA
turnover at nerve terminals as well as astrocytes and neurones. Whether synaptic actions of
BDNF can be triggered by adenosine released during hypoxic insults will also be evaluated.
BDNF has been also involved in the signalling between astrocytes and neurones. This may
involve a cascade of events shared by other purine receptors including ATP receptors (P2Y).
Since adenosine results from extracellular breakdown of ATP, it is highly important the
understanding of the interplay between adenosine and BDNF in this context.
Another ongoing project aims to elucidate how GABAergic inhibitory neurotransmission is

modulated by adenosine A1 and A2 receptors. GABA is the main inhibitory neurotransmitter in
the brain and adenosine is a main inhibitory neuromodulator. Therefore, the understanding of
how these neuromediators interplay is highly relevant for the understanding of how they protect
neurones from excessive excitability. By performing whole cell patch clamp recordings of
synaptic currents in hippocampal slices, as well as of ionic currents induced by iontophoretic
applications of GABA and glutamate, we will evaluate whether the modulation is exerted at the
pre- and/or post-synaptic level. Inhibitory synaptic currents will be recorded in pyramidal
neurones to evaluate the inhibitory input to excitatory neurones. To evaluate the excitatory input
to the inhibitory neurones, recordings will be made in the interneurones. The release of GABA
and glutamate from hippocampal synaptosomes will be measured by HPLC to directly assess
modulation of neurotransmitter release. The results to be obtained might prove useful in the
design of therapeutic strategies to control epilepsy or other pathologies involving unbalance
between inhibitory and excitatory transmission in the hippocampus.
A project in collaboration with the University of Groningen, Holland, aims to evaluate if the
upregulation of A1 adenosine receptors caused by interleukin 6 (IL-6, a neuroprotective
substance released by glial cells), observed by the group in Holland, has functional consequences
(to be tested by us). Electrophysiological recordings of synaptic potentials in hippocampal slices
pre-exposed to IL-6 are performed.
Canas, N., Pereira, I.T., Ribeiro, J.A. & Sebastião, A.M. (2004) Brain-derived neurotrophic
factor facilitates glutamate and inhibits GABA release from hippocampal synaptosomes through
different mechanisms. Brain Res. 1016:72-78. (Journal IF: 2.474) *
Cunha-Reis, D., Sebastião, A.M. Wirkner, K. Illes, P. & Ribeiro, J.A. (2004) VIP enhances both
pre- and postsynaptic GABAergic transmission to hippocampal interneurones leading to
increased excitatory synaptic transmission to CA1 pyramidal cells. Br. J. Pharmacol. 143:733-
744. (Journal IF: 3.611) *
Neurosci. 24:2905-2913. (Journal IF: 8.306) *
* These papers are also listed as publications from J. A. Ribeiro

Synaptic Plasticity Group

& Dementia Research Group
The main objective of the Synaptic Plasticity Group is to elucidate the mechanisms involved in
the modifications of neuronal communication after specific patterns of activity, the fundamental
biological process underlying learning and memory.
The impairment in memory and other cognitive functions associated with brain ageing is
assuming great importance and concern in our society. This is largely due to the fact that the
population is becoming older, and to the development of expectations that people can in fact
maintain physical and mental capacities until a very advanced age. The main objective of the
Dementia Research Group is the study of clinical, neuropsychological and other alterations
associated with brain ageing.
Principal Investigator
Alexandre de Mendonça, MD, PhD – Neurologist, Principal Investigator, IMM
Research Team
Ana Rita Costenla – PhD Fellowship, FCT

Vânia Cerqueira – Masters’s Degree Fellowship, FCT
Manuela Guerreiro, PhD, neuropsychologist, Principal Investigator, IMM

Filipa Ribeiro, biologist, PhD student, FML
Tiago Mendes, Master degree, Psychologist
Frederico Simões do Couto, MD, Psychiatrist, Assistant, FML
Ricardo Paiva Lopes, MD, Psychiatrist
Sandra Ginó, Psychologist
Sónia Silva, Psychologist
Research Areas
Memory
Brain Ageing
Mild Cognitive Impairment
Alzheimer's Disease
Dementia
Sebastião, A.M., de Mendonça, A., Moreira, T., Ribeiro, J.A. (2001) Activation of synaptic
NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs
recovery of synaptic transmission on reoxygenation. J. Neurosci. 21:8564-8571.
Almeida, C.G., de Mendonça, Cunha R.A., Ribeiro, J.A. (2003) Adenosine promotes recovery
from reactive oxygen species induced lesion in rat hippocampal slices. Neurosci. Lett. 339:127-
130. (Times cited: 3) (Journal IF: 1.967)
Rebola, N., Sebastião, A.M., de Mendonça, A., Ribeiro, J.A., Oliveira, C.R., Cunha, R.A. (2003)
Enhanced adenosine A2A receptor facilitation of synaptic transmission in the hippocampus of
aged rats. J. Neurophysiol. 90:1295-1303. (Times cited: 4) (Journal IF: 3.876)
Rebola, N., Coelho, J.E., Costenla, A.R., Lopes, L.V., Parada, A., Oliveira, C.R., Soares da Silva,
P., de Mendonça, A., Cunha, R.A. (2003) Decrease of adenosine A1 receptor density and of
adenosine neuromodulation in the hippocampus of kindled rats. Eur. J. Neurosci. 18:820-828.
Almeida, T., Rodrigues, R.J., de Mendonça, A., Ribeiro, J.A., Cunha, R.A. (2003) Purinergic P2
receptors trigger adenosine release leading to adenosine A2A receptor activation and facilitation
of long-term potentiation in rat hippocampal slices. Neuroscience 122:111-121.
Modulation by caffeine of neuronal functioning – a study by transcranial magnetic

stimulation (in collaboration with Professor Mamede de Carvalho, Electromyography and
Evoked Potentials Laboratory, IMM)
Caffeine is the most widely consumed psychotropic substance in the world. Regular consumers
frequently feel greater arousal and better intellectual performance after the intake of coffee.
Caffeine seems to render its consumer with the capacity for sharper responses and slightly
improves cognitive performance, especially if the individual is tired. The intake of caffeine
attenuates memory deficits induced by scopolamine, an amnesia-inducing substance, in healthy
volunteers.
It is likely that caffeine and other xanthines have a memory-enhancing effect, as they facilitate
synaptic plasticity - the phenomena of neuronal communication underlying memory. Long-term
potentiation (LTP), studied in brain slices of experimental animals, is an example of synaptic
plasticity. It is however unknown if the effects of cognitive facilitation in humans are also due to
the modulation of synaptic plasticity.
Transcranial magnetic stimulation has made it possible to study in humans the properties of
neuronal networks that reflect synaptic plasticity phenomena, notably by evoking short interval
responses induced by paired pulses. The main objective of this research project is to clarify the
electrophysiological mechanisms that underlie cognitive facilitation by caffeine.
2003/04 Project: Expression of proteins APP, PP-1, HSP e PARP in platelets from
patients Alzheimer’s disease, mild cognitive impairment and controls
(collaboration with Departamento de Biologia da Universidade de Aveiro, and
Centro Regional do Sul do Instituto Português do Sangue) (Sociedade Portuguesa
de Neurologia, starting 2003, duration 1 year).
2003/05 Project: Mild Cognitive Impairment: clinical, neuropsychological and NMR

study (collaboration with Centro de Ressonância Magnética de Caselas)
(Sociedade Portuguesa de Neurociências, starting 2003, duration 2 years)
Clinical Trials
Clinical Trial: TRIMCI – Triflusal in Mild Cognitive Impairment.
de Mendonça, A, Guerreiro, M, Ribeiro, F, Mendes, T, Garcia, C (2004) Mild cognitive

impairment: focus on the diagnosis. J. Mol. Neurosci. 23:13-17. (Journal IF: 2.812)
de Mendonça, A, Ribeir,o F, Guerreiro, M, Garcia, C (2004) Frontotemporal mild cognitive

impairment. J. Alzheim. Dis. 6:1-9. (Journal IF: 1.718)
de Mendonça, A, Ribeiro, F, Guerreiro, M, Palma, T, Garcia, C (2004) Clinical significance of

subcortical vascular disease in patients with mild cognitive impairment. Eur. J. Neurol. 11:1-6.
(Journal IF: 2.00)
Electromyography and Evoked Potentials Laboratory
The main objective of the Neuromuscular Group and Laboratory of EMG-Evoked Potentials is
the investigation of Neuromuscular Disorders, as well as the research in Clinical
Neurophysiology, in particular the techniques potentially applicable to study neuromuscular
conditions, regarding diagnosis, pathogenesis and measuring progression. New concepts, as
applying neurophysiology to understand the changes of chemical compounds on the nervous
system is another field we are working on. We are particularly interested in exploring the
interplay between clinical features and neurophysiology in order to develop new areas.
Mamede de Carvalho, MD, PhD – Auxiliary Professor, FML
Research Team
Teresinha Evangelista, MD
Isabel Coceição, MD
João Costa, MD
Anabela Pinto, MD
Ana Casaca - Investigator
Pedro Pereira - Technician
José Castro - Technician
Vitoria Ribeiro - Technician
Isabel Duran - Technician
Margarida Fernandes - Administrative Assistant
Research Areas
Neuromuscular Diseases
Amyotrophic Lateral Sclerosis
Amyloidosis
Myasthenia Gravis
Polyneuropaythies
Electromyography
Evoked Potentials
Magnetic Stimulation
de Carvalho, M., Michael Swash (2000) Nerve Conduction Studies in Amyotrophic Lateral
Sclerosis. Muscle and Nerve, vol 23:344-352, 2000. (Times cited: 17) (Journal IF: 2.450)
de Carvalho, M., Paulo Moreira, Teresinha Evangelista, José Luis Ducla-Soares, Mariana Bento,
Rui Fernandes, Maria João Saraiva. (2000) A New Transthyretin Mutation V28M in a Portuguese
Kindred with Amyloid Polyneuropathy. Muscle and Nerve, vol 23:1005-1015, 2000. (Times
cited: 10) (Journal IF: 2.450)
de Carvalho, M., Arminda Lopes, Manuel Scotto, Michael Swash (2001) Reproducibility of
Neurophysiological and Myometric Measurement in the Ulnar Nerve-Abductor Digiti Minimi
System. Muscle and Nerve, vol 24:1391-1395, 2001. (Times cited: 6) (Journal IF: 2.450)
Houlden, H., Steven Smith, Mamede de Carvalho, Julian Blake, Christopher Mathias, Nicholas
W Wood, Mary M Reilly (2002) Clinical and Genetic Characterization of Families with Triple A
(Allgrove) Syndrome. Brain, vol 125: 2681-2690, 2002. (Times cited: 9) (Journal IF: 7.122)
de Carvalho, M., Antónia Turkman, Michael Swash (2003) Motor Responses Evoked by
Transcranial Magnetic Stimulation and Peripheral Nerve Stimulation in the Ulnar Innervation in
Amyotrophic Lateral Sclerosis: the effect of upper and lower motor neuron lesion.
Journal of Neurological Sciences, vol 210:83-90, 2003. (Times cited: 4) (Journal IF: 2.140)
1996/05 Casa Pia Children´s Amalgam Trial (National Institute of Dental and
Craniofacial Research - USA)
2003/05 Amyotrophic Lateral Sclerosis. Clinical, Neurophysiological and Neurochemical

Investigation. Fundação para a Ciência e Tecnologia (POCTI/CBO/43952/2002)
2004/… Caffeine and Changes of the Motor Excitability – Neurophysiological Studies

(funding from “Cafés Delta” Company).
This set of projects is aimed to develop a number of techniques and neurophysiological tools to
increase our understanding of the mechanisms of neuromuscular diseases, early diagnosis, the
impact on the function, as well as the most appropriate way for measuring progression, in
particular for use in clinical trials.
de Carvalho, M., Swash, M. (2004) Cramps, Muscle Pain and Fasciculations – not always
benign? Neurology 63:721-723. (Journal IF: 5.678)
de Carvalho, M., Linke, R.P., Domingos, F., Evangelista, T., Ducla-Soares, J.L., Nathrath, W.,
Azevedo-Coutinho, C., Lima, R., Saraiva, M.J. (2004). Mutant Fibrinogen A-α-Chain Associated
with Hereditary Renal Amyloidosis and Peripheral Neuropathy. AMYLOID. The Journal of
Protein Folding Disorders 11:200-207. (Journal IF: 1.579 ) *
Geraldes, R., de Carvalho, M., Santos-Bento, M., Nicholson, G. (2004) Hereditary Sensory
Neuropathy Type 1 in a Portuguese Family - Electrodiagnostic and Autonomic Nervous System
Studies. Journal of Neurological Sciences 227:35-38. (Journal IF: 2.140)
Costa, J., Evangelista, T., Conceição, I., de Carvalho, M. (2004) Repetitive Nerve Stimulation in
Myathenia Gravis - Relative Sensitivity of Different Muscles. Clinical Neurophysiology 115:
2776-2782. (Journal IF: 2.485) *
Pinto, A., de Carvalho, M. (2004) Randomized Controlled Trial in Non-Invasive Ventilation.

What Trial? ALS and other Motor Neuron Disorders Vol 5:255-256. (Journal IF: 0.848)
Costa, C., Resende, C., de Carvalho, M. (2004) Motor-Axonal Polyneuropathy Associated With
Hepatitis C Virus. Hepatitis Review Journal Vol 1:24-26. (Journal IF)
Gouveia, R., Evangelista, T., Conceição, I., Pinto, A., de Carvalho, M. (2004) Abrupt Onset of
Progressive Muscular Atrophy (letter). ALS and other Motor Neuron Disorders Vol 5:61-62.
(Journal IF: 0.848) *
Swash, M., de Carvalho, M. (2004) Neurophysiological Index in ALS. ALS and other Motor
Neuron Disorders Vol. 5 (supp. 1) 108:110. (Journal IF: 0.848)
* These papers are also listed as publications from J. Pimentel

Neuropathology Laboratory
The Laboratory of Neuropathology of the Hospital de Santa Maria is incorporated in the

Neuroscience and Physiopathology Unit of the IMM, and fulfils three major roles: diagnostic,
teaching and research. Related to the fact that it diagnoses mainly brain tumors and muscular
diseases, our research activity concerns mainly these pathologies.
Moreover, and related to the fact that the neurological and neurosurgical departments are very
active in studing and operating on epilepsy, we are also devoted to the neuropathological aspects
of epilepsy surgery.
Finally, and related once again to the fact of the Laboratory of Neuropathology being one of the
few portuguese reference centers for human prion disease (HDP), we are also interested on the
histopathological features of HPD, namely Creutzfeldt-Jakob Disease (CJD).
José Pimentel, MD, PhD – Full Professor, FML
Research Team
Teresinha Evangelista, MD
Cândida Barroso, MD
Carla Firmo, Histotechnologist
Pedro Pereira, Histotechnologist
Helena Simões, Histotechnologist
Maria Gabriela Baptista, Secretary
Research Areas
Pathology and proliferative activity of brain tumors

Brain tumors epileptogenesis
Neuropathology of epilepsy surgery
Epidemiological and pathological features of HPD
Miopathies
Pathology and proliferative activity of brain tumors – We investigate the histopathological

features of brain tumors, mainly gliomas, trying to establish new or unusual morphological and/or
immunohistochemistry features. We also focus on the correlation between anaplasic features of
brain tumors and their biological behaviour, namely by using anti-proliferative antibodies.
Brain tumors epileptogenesis – Epilepsy associated to brain tumors is classically due to injury
of perilesional tissue. However, tumoral tissue itself may also be epileptogenic. On the other
hand, some variants of gliomas are prone to bigger incidences of epilepsy and, on the other hand,
their anaplastic grades are linked to different seizures incidences. We are studding, by applying
immunohistochemical methods, the neurochemical profile of different gliomas concerning
excitatory and inhibitory neurotransmission, trying to correlate this profile with the occurrence of
seizures. We are using antibodies anti-glutamate receptors (NMDA) and glutamate
descarboxylase, and anti-GABA receptors.
Neuropathology of epilepsy surgery – We are studying tissue material from epilepsy surgery
(both from neocortical, and mesial temporal pathology), and we aim to perform tissue
investigation regarding epileptogenesis on this material.
Epidemiological and pathological features of HPD – By post-mortens, we are studying the

histopathological features of CJD, trying to correlate them with clinical features, positivity of
CSF protein 14.3.3, and genetics (codon 129 of prion gene). We are also engaged in
epidemiological surveillance of CJD in Portugal.
Miopathies – We are studding the histopathological features of several miopathies, namely

congenital ones, by using, among other technician, antibodies against selected proteins involved
in these diseases.
Creutzfeldt-Jakob Disease: epidemiology, risk factors, diagnostic and genetics – NEUROCJD

Concerted Action (QLK2 2001 02248).
Gil-Gouveia, R., Cristino, N., Farias, J.P., Trindade, A., Ruivo, N.S., Pimentel, J. (2004)
Pleomorphic xanthoastrocytoma of the cerebellum: illustrated review. Acta Neurochir. 146:1241-
1244. (Journal IF: 0.977)
de Carvalho, M., Linke, R.P., Domingos, F., Evangelista, T., Ducla-Soares, J.L., Nathrath, W.,
Azevedo-Coutinho, C., Lima, R., Saraiva, M.J. (2004). Mutant Fibrinogen A-α-Chain Associated
with Hereditary Renal Amyloidosis and Peripheral Neuropathy. AMYLOID. The Journal of
Protein Folding Disorders 11:200-207. (Journal IF: 1.579 ) *
Costa, J., Evangelista, T., Conceição, I., de Carvalho, M. (2004) Repetitive Nerve Stimulation in
Myathenia Gravis - Relative Sensitivity of Different Muscles. Clinical Neurophysiology 115:
2776-2782. (Journal IF: 2.485) *
Gouveia, R., Evangelista, T., Conceição, I., Pinto, A., de Carvalho, M. (2004) Abrupt Onset of
Progressive Muscular Atrophy (letter). ALS and other Motor Neuron Disorders Vol 5:61-62.
(Journal IF: 0.848) *
* These papers are also listed as publications from M. de Carvalho

Functional Neuroanatomy Laboratory

The Neuroanatomy Laboratory main objective is the research of Applied Central Nervous System
Morphology. The actual major fields of interest of its activity are the Medial Temporal Lobe
Morphometry and the Brainstem Stereotaxy.
Ongoing research in the Neuroanatomy Laboratory includes a project on Hippocampal Complex

Volumetry and another on Locus Ceruleus Stereotactic Anatomy. These projects have already
given consistent results and are now being developed towards further objectives, and publication.
During the present year another project, on the Human Nucleus Accumbens, is supposed to begin.
Among further developments there are some methodological and technical innovations intended
to promote bridging points of converging interest with other groups and laboratories in the IMM.
A.J. Gonçalves Ferreira, MD, PhD – Tutor of GAPIC investigators, Full Professor, FML
Research Team
Lia Neto, MD, Master Degree student – Co-tutor of GAPIC investigators, Assistant, FML
Paula Fernandes, Medical student – GAPIC investigator, Assistant, FML
Tiago Fonseca, Medical student – GAPIC investigator
Hugo Gaspar, Medical student – GAPIC investigator
Carolina Gonçalves, Medical student – GAPIC investigator
Francisco Santos, Medical student
Marta Nogueira, Medical student
Maria Afonso, Medical student
Joana Regala, Medical student
José Pinto, Medical student
Research Areas
Cerebral Microsurgery Anatomy

Brainstem Stereotactic Anatomy
Hippocampus Neuroanatomy
Hippocampal Complex Volumetry (no current funding)
The goal of this project is to study the normal human hippocampal volume and its variations –
side to side, with gender and age – which is essential to establish the patterns of age-related
volume evolution and its asymmetries and to define the correct criteria for the diagnosis of
hippocampal atrophy.
From previous works it was possible to determine the normal hippocampus volume and its
variations, as well as validate Magnetic Resonance Imaging (MRI) as a reliable method of
measuring hippocampus volumetry.
The present objective of our research is: 1) to enlarge the study of the normal human
hippocampus to obtain statistically significative results concerning interhemispheric differences
and age and sex variations; 2) to analyze the volume and morphology of the different
hippocampus sectors.
Locus Ceruleus Stereotatic Anatomy (no current funding)
The aim of this project is to define the exact dimensions and 3-D localization of the locus
ceruleus in relation to reliable 3-D anatomical landmarks so it can be easily referred on MRI or in
open or closed surgical procedures.
Following the works of previous years it was possible to determine the accurate stereotactic
location of this nucleus, based on 3-D probability volume studies, as well as its dimensions,
remarkably larger than once thought.
The objective of the present research is: 1) to extend this study to a larger number of cases in
order to obtain statistically significant results; 2) to study case-to-case volume and localization
variability.
EEG/Sleep Laboratory
The Sleep EEG group is a multidisciplinary team, with a heavy involvement and responsibility in
routine health care and in pre and post graduate teaching. Pre graduate teaching includes the field
of Biomedical Engineering, while post graduate is centred in the Master Degree of Sleep
Medicine and in the collaboration with the Master Degree in Neurosciences.
With these actions the group aims high level academic work, applied medical research and
scientific dissemination. The ultimate objective is the formation of a critical mass of young
scientists and healthcare professionals, able to invest in a multidisciplinary work in the target
areas.
These objectives can be drawn from the achievements in 2004. Specifically they aim international
and multilingual dissemination of Sleep and Sleep disorders via Information Society technology
(European project). Research in the area of dreams and their psycho and neurophysiological
correlates (Master and PhD Thesis and projects. Research in fields with high impact in society
(accidents) (Post Doc work). Research in specific fields of Sleep Medicine and Chronobiology
(Master Thesis and projects).
Teresa Paiva, MD, PhD – Associated Professor, FML, Senior Staff Neurologist, HSM
Research Team
Carla Bentes, MD
Marta Gonçalves, MD, MSc
Hélder Bértolo, Physicist, MSc - PHD student
Ruth Geraldes, MD – Master’s degree student
Ana Rita Peralta, MD – Master’s degree student
Ana Nunes, MD – Master’s degree
Tiago Mestre, MD – Master’s degree student
Pedro Rocha, Eng.
Rosa Santos - EEG Technologist
Isabel Henriques - Secretary
Research Areas
Sleep and EEG

Information Society - Telemedicine
Paiva, T., H. Coelho, M. Teles Araújo, R. Rodrigues, A. Almeida, T. Navarro, M. Cruz, G.

Carneiro, C. Belo (2001) Neuroconsultation for General Practitionners. Journal of Telemedicine
and Telecare 7:007-3b.1-6. (Times cited: 0) (Journal IF:1.351)
Penzel, T., K. Kesper, T. Paiva, G. Mayer, J. Zulley (2001) The European Neurological Network
Database and Sleep Atlas: A Neurological Signals Database for Increasing Knowledge and
Awareness of Sleep Disorders. IEEE in Medicine and Biology 20(3):63-69.
Ohayon, M.M., RG Priest, J. Zulley, S. Smirne, T. Paiva (2002) Prevalence of Narcolepsy

Symptomatology and Diagnosis in the European General Population. Neurology 58:1826-1832.
Bértolo, H., T. Paiva, L. Pessoa, T. Mestre, R. Marques, R. Santos (2003) Visual Dream Content,
Graphical Representation and EEG Alpha Activity in Congenitally Blind Subjects. Cognitive
Brain Research 15: 277-284. (Times cited: 3) (Journal IF: 2.865)
Gonçalves, M.A., MD; Teresa Paiva, MD; Elizabeth Ramos, MS; and Christian Guilleminault,
MD, BiolD (2004) Obstructive Sleep Apnea Syndrome, Sleepiness, and Quality of Life. Chest
2003/04 Economic evaluation of Doctor-to-Doctor Teleconsultation – Comparison with

Standard Specialized Consultations. Fundação para a Ciência e Tecnologia
(POCTI/ESP/43099/2001)
“Sonhos em Surdos: alterações oníricas por déficite sensorial” Fundação Bial. 2

years.
Influência da foto estimulação ocular e cutânea na organização circadiária do

ciclo sono-vigília em humanos cegos e normovisuais. Fundação para a Ciência e
Tecnologia (POCTI/CBO/45867/2002)
2005/06 ETEN/2004/1 – ENN-ICS – European Neurological Network – Interactive

Communication System, Contract 517418 – European Commission- TenTelecom
– eten. Application and contract discussion in 2004.
Gonçalves, M.A., MD; Teresa Paiva, MD; Elizabeth Ramos, MS; and Christian Guilleminault,
MD, BiolD. (2004) Obstructive Sleep Apnea Syndrome, Sleepines, and Quality of Life. Chest
125:2091-2096. (Journal IF: 3.264)
Paiva, T., Thomas Penzel, Juergen Zulley, Colin Binnie, Michel Russel, Pierre Escourrou,
Madalena Teles Araujo, Ana Fred, Alpo Varri, Manfred Spreng, Kim Nielsen, Calor Belo,
Agostinho Rosa and Christian Guilleminault (2004) The ENN Project – A Telematics
Experience in Neurology. Somnology 8:3-13. (Journal IF -)
Guilleminault, C., C.M Lin, M. Gonçalves, E. Ramos (2004) A Prospective Study of Nocturia
and the Quality of Sleep of Elderly Patients with Obstructive Sleep Apnea or Sleep Onset
Insomnia. Journal of Psychosomatic Research 56: 511-5. (Journal IF: 2.019 )
Autonomic Nervous System Unit

Description and objectives
The main goal of this autonomic nervous system unit (ANSU) is the understanding of the
mechanisms underlying the function of the autonomic nervous system in both physiological and
physiopathological conditions. To fulfil this purpose research is carried out both in animal models
(in vivo experiments) and in human subjects. In animals (rats and rabbits) electrical and chemical
stimulation of central nervous system areas (e.g., nucleus tractus solitarius, rostroventrolateral
medulla, sublobule IX-b of the cerebellum and hypothalamic defence area) modifies the
autonomic outflow that can be evaluated by analysing the autonomic evoked responses at the
cardiovascular and respiratory systems. Also, in animal models extra and intracellular recordings
of cell activity in some of the previous central nervous system areas, which integrate afferent
sensory information, are routinely performed. In humans, our studies relate mainly with
adaptation to both passive and active orthostathism in which autonomic adaptation plays an
essential role. Also patients showing diabetes, hypertension, Parkinson disease and orthosthatic
syncope are object of our studies since their clinical condition reveals a dysautonomy. The
analysis in the frequency domain of cardiac variability and blood pressure by Fast Fourier
Transform (FFT) is currently used in our laboratory to access autonomic nervous system
Coordinator
Luís Silva-Carvalho, MD, PhD – Full Professor, FML
Other Principal Investigators
José Ducla Soares, Associate Professor, FML (Professor Associado com Agregação)
Research Team
Alberto Escalda - Auxiliary Professor, FML

Basílio Gomes Pinto - Invited Auxiliary Professor, FML
Carlos Marques Neves – Assistant, FML
Eduardo Teles Martins - Invited Auxiliary Professor, FML
Francisco Araújo, MD - Internal Medicine, Montijo Hospital
Isabel Rocha - Associate Professor, FML
Luís Brás Rosário - Invited Assistant, FML
Maria do Amparo Barros – Technician, FML
Maria Joaquina Bettencourt -Auxiliary Professor, FML
Mariana Bento, MD, Neurology
Sandra Garcês, MD - Internal Medicine, Hospital de Santa Maria
Victor Gonçalves - Invited Assistant, FML
Research Areas
Autonomic nervous system- physiology and physiopathology

Biological signal processing
Silva-Carvalho, L., Dawid-Milner, M.S., Goldsmith, G.E. and Spyer, K.M. (1995) Hypothalamic
modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus
tractus solitarii. J. Physiol. 487.3:751-760. (Times cited: 18) (Journal IF: 4.352 )
Dawid-Milner,M.S., Silva-Carvalho, L., Goldsmith, G.E. and Spyer, K.M. (1995) Hypothalamic
modulation of laryngeal reflexes in the anaesthetized cat: role of the nucleus tractus solitarii. J.
Physiol. 487.3:739-749. (Times cited: 15) (Journal IF: 4.352 )
Silva-Carvalho, L., Dawid-Milner, M.S. and Spyer, K.M. (1995) The pattern of excitatory inputs
to the nucleus tractus solitarii evoked on stimulation in the hypothalamic defence area in the cat.
J. Physiol. 487.3.727-737. (Times cited: 17) (Journal IF: 4.352 )
Zagon, A., Rocha, I., Ishizuka, K. and Spyer, K.M. (1999) Vagal modulation of responses elicited
by stimulation of the aortic depressor nerve in neurons of the ventrolateral medulla oblongata of
the rat. Neuroscience 92(3):877-888. (Times cited: 8) (Journal IF: 3.601 )
Rocha, I., Burnstock, G. and Spyer, KM. (2001) Effect on urinary bladder function and arterial
blood pressure of the activation of putative purinoceptors of brainstem areas. Aut. Neurosc.: basic
and clinical 88:6-15. (Times cited: 6) (Journal IF: 0.930)
Purines and the central nervous system control of autonomic function, (POCTI/FCB/37332/2001)
DIE-HEART: Diagnostic improvement of echocardiography by quantitative assessment of heart,

(POCTI/CBO/43940/2001)
Erectil disfunction avoidance after prostate surgery: development of a neurotropic dye. (Invest.
em Oncologia NRS/LPCC – “Terry Fox – 2003-2004”)
During 2004, we focused on the development of the analysis of autonomic efferences using new
methods on the frequency domain such as wavelets. The FFT allows the analysis of signals in
stable periods of at least five minutes of recording, which has been a limiting factor as transient
phenomena of a lower duration such as autonomic reflexes, postural changes or brief stimuli
escape to this analysis. By applying wavelets we showed that this short time analysis is possible
(communication and publications in 2004). This method that we firstly used on animal studies
started to be applied in our patients and in a project of collaboration with the group of Professor
Queiroz e Melo which purpose is to study patients with atrial fibrillation that is treated by surgical
procedures.
Another goal of 2004 was the development of a digital model of an impedance plethysmograph
that allowing the recording of intraventricular volumes in real time during the cardiac cycle will
be an important tool for the evaluation of cardiac function both in the research and clinical fields.
This is based in an analogical model developed in the Institute of Physiology during the 1970’s.
The new digital model is now under testing.
Also in 2004 the majority of experiments related with three lines of research that are included in
the three submitted PhD thesis were completed. The great majority of this research material has
been communicated and published in 2003 and 2004 being some of it, in the moment, under
submission. These lines are:
- autonomic influences in ocular circulation : as result, a new non-invasive method to

analyse autonomic efferences to the eye is now being developed for testing in animals
during 2005;
- cerebellar control of the cardiovascular function: as a result, a non-invasive evaluation of
autonomic function with surgical cerebellar pathology will be implemented during 2005;
- dysautonomy in acute heart ischemia: the involvement of the central angiotensin system
has been clearly proved as well as a stronger indication of the involvement of the
hypothalamic defence area (HDA) in the disturbances of autonomic outflow that are
currently observed in these patients; also, during 2004, other animal experiments
(Diploma thesis) confirmed the involvement of HDA on this autonomic disturbances. A
program of autonomic evaluation of patients with recent episodes of heart ischemia will
start in 2005.
In beginning of 2004, contacts were made with the Physiology Department of the Oporto Medical
School (Professor Adelino Leite Moreira) in order to complement expertises from both groups on
the study of cardiovascular physiology. On this scope preliminary experiments were carried out in
both laboratories during the 2nd half of 2004 that will be routinely performed in 2005. This
experiments will focus on the analysis of C-fos expression in the NTS of animals submitted to
increases of the left ventricular afterload as well as the study of changes in the expression of
enzymes related with calcium metabolism in ventricles of rats submitted to HDA activation.
Carvalho, M., Limka, R.P., Evangelista, T., Ducla-Soares, J.L., Maturata, B.J., Azevedo-Lima,
R., Saraiva, M.J. (2004) Mutant fibrinogen associated with renal amyloidosis peripheral
neuropathy. Amyloide 11:200-207. (Journal IF: 1.579)
Marques-Neves, C., Martins-Baptista, A., Boto, J.P., Delgado, E., Silva-Carvalho, L., Rocha, I.
(2004) Intraocular pressure variability in the anaesthetized rat: a spectral analysis. Eur. J.
Ophthalmol. 14(5):381-386. (Journal IF: 0.039)
Postolache, G., Rocha, I., Postolache, O., Silva-Carvalho, L., Girão, P. (2004) A wavelet based
approach for monitoring baroreceptors function test in rats. IMTC/IEEE, 844-849. (Journal IF)
Rocha, I., Silva-Carvalho, L., Spyer, K.M. (2004) Effect of stimulation of anterior hypothalamic
area on urinary bladder function of the anaesthetised rat. Clin. Aut. Res. 14(4) :264-269.
(Journal IF: 1.237)
Clinical Neurology Research Unit

Coordinator
José M. Ferro, MD, PhD, Associate Professor, FML/HSM
Ultrasound Cerebral Hemodynamics Laboratory

Cerebrovascular Diseases Group
Our mission is part of the general objective of the Clinical Neurology Research Unit. The aim is
to study the clinical epidemiology of diseases involving the nervous system. The work of the
NCRU research will focus on large samples and on prevalent, disabling, chronic CNS conditions
such as dementia, stroke and Parkinson’s disease. Our aim is to identify risk factors, including
ecological and genetic ones, and prognostic factors leading from an independent life to
dependency or death, and on the development and assessment of therapeutical interventions that
could be able to delay or prevent transition from a healthy, independent state to disability and
death. Measures of disability will include neurophysiological and quality of life dimensions. The
large samples of patients afflicted with stroke conditions will offer a unique opportunity for
detailed neuropsychological and neuroimaging studies and the development and testing of
cognitive neuropsychological models.
The Unit has an additional aim of training young medical and non-medical clinical researchers
and to disseminate an evidence-based and patient-oriented view of the research and practice in
Clinical Neurosciences.
José M. Ferro, MD, PhD, Associate Professor, FML/HSM
Research Team
Vitor Oliveira, MD, PhD - Auxiliary Professor, FML / HSM

Teresa Pinho e Melo, MD, HSM
Patricia Canhão, MD - Auxiliary Professor, FML / HSM
Filipa Falcão, MD, HSM
Ana Verdelho, MD, HTV
Sofia Madureira, PsyD, Fellow
Lara Caeiro, PsyD
Catarina Santos, PsyD, Fellow
Paulo Batista, Technician, HSM
Fátima Soares, Technician, HSM
Research Areas
Stroke
Clinical epidemiology of stroke and vascular cognitive impairment
Vascular dementia
Vascular cognitive impairment
Pinto, A.N., Melo, T.P., Lourenço, M.E., Leandro, M.J., Brázio, A., Carvalho, L., Franco, A.S.,
Ferro, J.M. (1998) Can a clinical classification of stroke predict complications and treatments
during hospitalisation? Cerebrovasc. Dis. 8:204-209. (Times cited: 22) (Journal IF:1.665)
Batista, P., Oliveira, V., Ferro, J.M. (1999) The detection of microembolic signals in patients at
risk of recurrent cardioembolic stroke: possible therapeutic relevance. Cerebrovasc. Dis. 9:314-
319. (Times cited: 11) (Journal IF: 1.665)
Ferro, J.M., Correia, M., Pontes, C., Baptista, Pita, M.V. (2001) for the Cerebral Venous
Thrombosis Portuguese Collaborative Study Group (Venoport). Cerebral Vein and Dural Sinus
Thrombosis in Portugal: 1980-1998.Cerebrovasc. Dis. 11:177-182.
Ferro, J.M., Lopes, M.G., Rosas, M.J., Ferro, M.A., Fontes, J. (2002) for the Cerebral Venous
Thrombosis Portuguese Collaborative Study Group (VENOPORT). Long-term prognosis of
cerebral vein and dural sinus thrombosis. Results of the VENOPORT Study. Cerebrovasc. Dis.
Matias-Guiu, J., Ferro, J.M., Alvarez-Sabin, J., Torres, F., Jimenez, M.D., Lago, A., Melo, T.
(2003) Comparison of triflusal and aspirin for prevention of vascular events in patients after
cerebral infarction: the TACIP Study: a randomized, double-blind, multicenter trial. Stroke
1998/06 Impact of Age-related brain white matter changes on transition to disability in the
elderly. Leukoaraiosis And DISability.
1998-2002 Fifth (EC) Framework Programme 1998-2002 – “Quality of life and management
of living resourses”: QLK6-2000-00446.
1998/08 Tromboses venosas cerebrais - Estudo prospectivo multinacional.

Programa PRAXIS XXI - Ciências da saúde: PRAXIS/P/SAU/10248/98
2000/06 Psychiatry of acute stroke – financed by ADIDVC (Associação para a o

Desenvolvimento e Investigação da Doença Vascular Cerebral
Impact of Age-related brain white matter changes on transition to disability in the elderly.
Leukoaraiosis And DISability
The introduction of neuroimaging techniques (CT, MRI) has led to recognize with increasing
frequency changes in the cerebral subcortical white matter, called leukoaraiosis by Hachinski et
al. [1987]. These alterations are observed with the highest frequency in elderly subjects,
particularly in those with vascular risk factors [Pantoni and Garcia, 1995]. Based on this
epidemiological consideration, the term Age-Related White Matter Changes (ARWMC) has been
chosen for the present study.
The pathogenesis of these changes is not yet completely elucidated, and the pathological changes
of intraparenchymal small arteries and arterioles consequent to ageing and arterial hypertension
are thought to represent the underlying vascular cause, in combination with fluctuations of
systemic blood pressure (Pantoni and Garcia, 1997).
Most of the studies reporting functional and clinical abnormalities in patients with ARWMC are
consistent in indicating an association with global dementia or selective cognitive deficits,
depression, motor abnormalities, particularly gait impairment (Pantoni and Garcia, 1995;
Longstreth et al., 1996). Notoriously, these deficits are main contributors to disability in the
elderly.
Pathological processes involved in the transition from an independent to a disability status in the
elderly are still incompletely defined. Standardized tools and modern laboratory techniques may
help identifying these processes. Large subjects/patients cohorts of patients with ARWMC of
different severity, careful baseline assessment of risk factors, and detailed follow-up observation
may lead to elucidate these issues. The present study primarily aims, through a longitudinal
design, to provide more advanced and conclusive evidence that ARWMC play an independent
role as determinant of transition to disability in the elderly. Other questions relating to other
selective clinical or functional outcomes may be answered owing to such design. If the role of
ARWMC in relation to disability in the elderly is demonstrated, intervention strategies for
prevention, drug treatment, rehabilitation, and care can be designed in order to prevent or delay
the transition linked with ARWMC.
The objectives of the study are summarized as follows:
1) To evaluate age-related cerebral white matter changes (ARWMC) as independent

determinant of the transition from healthy status to disability in elderly individuals. To
this end, patients with ARWMC of different severity and no or mild disability will be
followed-up for a period of 3 years to determine the proportion changing to a more severe
disability status.
2) To establish whether ARWMC is an independent predictor of: i) death from any cause or
specific causes, ii) dementia, iii) cardiovascular events, iv) depression.
3) To study progression of ARWMC on MRI images in relation to the functional and
clinical outcomes.
4) To determine quality of life in subjects with ARWMC of different severity degree on
baseline and at the end of follow-up.
5) To settle and validate criteria for identifying possible Cerebral Autosomal Dominant
Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL] cases on a
clinical and MRI basis.
Tromboses venosas cerebrais - Estudo prospectivo multinacional
The majority of studies on cerebral vascular disease have concentrate on the arterial side of the
cerebral circulation. Thrombosis of the cerebral veins and dural sinus (CVDST) appeared to be
relatively uncommon pathology. Nevertheless the experience of individual centres with CVDST
is usually limited to a few new cases each year. Similarly small acute CVDST trials provided
conflicting results regarding their pharmacological treatment on the acute phase. Hence
information on several aspects of its prognosis and management are largely based on anedoctical
evidence and have not been addressed by adequately powered large scale studies. The ISCVT is a
multicentre, multinational prospective observational study on CVDST, whose primary objectives
are to describe the long-term prognosis of CVDST and to identify predictors of outcome,
including variability on CVDST management and a risk factors/associated conditions. During the
1st phase ISCVT succeeding in enrolling 615 patients whose follow-up was concluded by the end
of 2001.
The secondary objectives of ISCVT 2nd phase are:
1) To evaluate the role of oral contraceptive, prothrombotic genetic mutations and defects of
fibrinolysis on CVDST.
2) To perform a systematic review of thrombolysis and steroid therapy in acute CVDST.
3) To describe the mechanisms of acute death in CVDST.
The results of the study will provide clinical relevant information on the diagnosis, predisposing
condition, including prothrombotic genetic mutations, prognosis, and on current management of
this condition. A subset of patients at risk of not fully recovery was identified. The feasibility and
safety of aggressive medical interventions will be determined in an intervention trial of local
thrombolysis.
Psychiatry of acute stroke
Several psychiatric symptoms, disturbances and disorders have been described in connection with
acute stroke and also in stroke survivors disturbing rehabilitation. Nearly all the studies published
so far were conducted in rehabilitation units including non-acute stroke patients. An emphasis has
been placed on mood disorders by using adequate instruments for screening these disorders, but
in the absence of other disturbances, as delirium. Moreover, diagnostic labels for these conditions
have been used regardless of the specific criteria defined by accepted international mental
disorders classifications. Minor changes in behaviour, some unclassifiable as specific disorders,
but still with a predictable impact on outcome were not systematically recorded. Several other
studies that we made concluded that several other neurological and neurochemical factors were
independent risk factor to the development of some psychiatric disturbances. However it has not
been made a systematic study of theses other risk factors. Regarding follow-up, neither repeating
clinical assessment nor the administration of psychometric instruments had been systematically
used and compared with the presence of psychiatric disturbances in acute phase. This causes an
obvious difficulty in establishing diagnostic consistency and steadiness over time. Psychiatric
sequelae as a whole and their negative impact on rehabilitation certainly need further research
concentrating both on the very earlier moments of its precursors as well as their evolution over
time.
The main objectives of this project are the systematic and quantitative study of cognitive
disturbances, delirium, depression and anxiety developing in the acute phase of stroke and the
evolution within a three years period. An attempt to relate these change with neurological and
neuropsychological/neuropsychiatric deficits, inability degree, life impairments and imaging data
(CT, Perfuson CT, Diffuson MR), will be made. The impact of psychiatric change on patients’
quality of life, as well as the repercussions of all psychiatric disturbances in their caregivers will
be assessed.
Subjects will be acute stroke patients consecutively admitted to a stroke unit during a 15-month
period (nº required 250 patients). Acute (day 0 to 4) assessment will consist of standardised
neurological and imaging (acute CT, acute perfusion CT, diffusion MR) evaluation, grading of
stroke severity and disability. Additionally, it will be made a measure of the plasma
acetylcholinesterase and butyrylcholinesterase activity, grading anticholinergic levels in blood. A
bed-side cognitive screening and a neuropsychiatric/neuropsychological evaluation including a
descriptive semi-strutured data base and interview to assess cognition, delirium, depression and
anxiety.
Follow up will be performed at 1st, 6th 12th months and 2nd and 3rd years after stroke onset and
will consist of neurological and disability evaluation, repeated imaging for hemorrhagic/ischemic
strokes, an exhaustive neuropsychiatric/neuropsychological evaluation and also an assessment of
the daily activities and of the quality of life, and their repercussion in caregivers. Apathy,
delirium, depression, anxiety, quality of life, disability rating scales will be used. These scales
will also be assessed in caregivers of dependent patients to assess anxiety, depression and coping.
Results from this study will provide a comprehensive description of behavioural changes
occurring in the acute stroke setting, as well as their long-term outcome, an analysis of their
relationship with the neurological defect, disability and the site and size of the brain lesion. Their
impact on the long-term quality of life of stroke survivors, the life disabilities, the cognitive
disturbances, the coping and anxiety and the depressive disturbances will be determined. These
data will be instrumental for conceptual models dealing with the “emotional brain”. They will be
very helpful to point out the needs for psychiatric/psychological assessment, counselling and
treatment of stroke victims and their caregivers.
Brainin, M., Olsen, T.S., Chamorro, A., Diener, H-C, Ferro, J., Hennerici, M.G., Langhorne, P.,
Sivenius, J. for the EUSI Executive Committee and the EUSI Writing Committee (2004)
Organization of stroke care: education, referral, emergency management and imaging, stroke
units and rehabilitation. Cerebrovasc. Dis. 17(suppl.2):1-14. (Journal IF: 2.030)
Ferro, J.M. (2004) Patterns of ischaemic cerebral disease. J. Neurol. 251:1-10.

(Journal IF: 2.778)
Caeiro, L., Ferro, J.M. Albuquerque, R., Figueira, M.L. (2004) Delirium in the first days of acute
stroke. J. Neurol. 251:171-178. (Journal IF: 2.778)
Verdelho, A., Hénon, H., Lebert, F., Pasquier, F., Leys, D. (2004) Depressive symptoms after
stroke and relationship with dementia. A three-year follow-up study. Neurology 62:905-911.
(Journal IF: 5.678)
Bousser, M-G, Castel, J-P, Ducros, A., Ferro, J., Kittner, S., Mattle, H., Olesen, J., Solomon, S.
(2004) Working group on Headache attributed to non-vascular intracranial disorder. The
International Classification of headache disorders. Cephalalgia 24(supp.l.):65-76.
Ferro, J.M., Canhão, P. Stam J., Bousser M.G., Barinagarrementeria F., ISCVT Investigators.
(2004) Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study
on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 35:664-670. (Journal IF: 5.233)
Coelho, M., Ferro, J.M. (2004) Fou rire prodromique: reply to a note. Cerebrovasc. Dis. 17:349-
350. (Journal IF: 2.030)
Ferro, J.M. (2004) Atrial fibrillation and cardioembolic stroke. Minerva Cardioangiol. 52:111-
124. (Journal IF -)
Ferro, J.M. Pinto, F. (2004) Poststroke epilepsy. Epidemiology, pathophysiology and

management. Drugs Aging 21:639-653. (Journal IF: 2.799)
Correia, M., Silva, M.R., Matos, I., Magalhães, R., Castro Lopes, J., Ferro, J.M., Silva, C. (2004)
Prospective Community-based study of stroke in Northern Portugal. Incidence and case fatality in
rural and urban populations. Stroke 35:2048-2053. (Journal IF: 5.233)
Deplanque, D., Leys, D., Parnetti, L., Schmidt, R., Ferro, J., De Reuck, J., Mas, J-L, Gallai, V.
and SAFE II Investigators (2004) Stroke prevention and atrial fibrillation: reasons leading to an
inappropriate management. Main results of the SAFE II study. Br. J. Clin. Pharmacol. 57:798-
806. (Journal IF: 2.531)
Caeiro, L., Ferro, J.M., Claro, M.I., Coelho, J., Albuquerque, R., Figueira, M.L. (2004) Delirium
in acute stroke: a preliminary study of the role of anticholinergic medications. Eur. J. Neurol.
11:699-704. (Journal IF: 2.00)
Ciccone, A., Canhão, P., Falcão, F., Ferro, J.M., Sterzi, R. (2004) Thrombolysis for cerebral vein
and dural sinus thrombosis. Stroke 35:2428. (Journal IF: 5.233)
Publications of Multicentre Collaborative Studies with Collective Authorship
Diener, H-C, Bogousslavsk, J., Brass, L.M., Cimminiello, C., Csiba, L., Kaste, M., Leys, D.,
Matias-Guiu, J., Rupprecht, H-J on behalf of the MATCH Investigators (2004) Aspirin and
clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic
attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet
364:331-337. (Journal IF: 18.316)
The ONTARGET/TRANSCEND Investigators (2004) Rationale, design, and baseline

characteristics of 2 large, simple, randomised trials evaluationg telmisartan, ramipril, and their
combination in high-risk patients: The ongoing Telmisartan Alone and in Combination with
Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant
Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am. Heart. J. 148:52-
61. (Journal IF: 3.3
Language Research Laboratory
The main objective of this Unit is to investigate the biological basis of human cognition and
behaviour in particular Language and Memory, and its changes along normal development and
aging. This is accomplished by the neuropsychological study of patients with different brain
lesions and the rehabilitation and follow-up of aphasic subjects and patients with dementia.
An additional line of clinical research includes the study of craniofacial pain and is undertaken in
the Headache Outpatient Clinic of Hospital de Sta Maria, coordinated by Isabel Pavão Martins.
Our main interest is the clinical characterization of the trigemino vascular and trigemino-
autonomic cephalalgias.
The main objective of the group leaded by Alexandre Castro-Caldas is the study of the influence
of schooling on the biofunctional organisation of the brain.
Principal Investigadors
Alexandre Castro-Caldas, MD, PhD

Isabel Pavão Martins, MD, PhD – Auxiliary Professor, FML
Research Team (PI – Isabel Pavão Martins)

Manuela Guerreiro, PhD - Auxiliary Professor, FML
Martin Lauterbach, MD, PhD - Post-doc Fellowship, FCT
Luisa Albuquerque, MD - Neurologist, HSM
Clara Loureiro - Research Fellow
Filipa Ribeiro, PhD student
Gabriela Leal - Speech Therapist, HSM
Maria Luisa Farrajota - Speech Therapist, HSM
José Fonseca - Speech Therapist, FML
Rita Lopes da Silva, MD - Assistant FML, Research Volunteer
Raquel Gil-Gouveia, MD - Neurology Resident
Susana Rodrigues, Psychologist - Research Volunteer
Sandra Ginó, Psychologist - Research Volunteer
Research Team (PI – Alexandre Castro-Caldas)

Vânia Nunes - Bolseiro de Doutoramento, FCT
Sara Cavaco - Bolseiro de Doutoramento, FCT
Marta Gonçalves - Bolseiro de Doutoramento, FCT
Rita Simões – Internato de Medicina, HSM
Research Areas
Neurologia comportamental
Dor Cranio-facial
Influência da escolaridade na organização bio-funcional do cérebro.
1997/… “Casa Pia Children’s Amalgam Trial”. Collaboration between: Faculdade de

Medicina Dentária /FML/ Department of Psychiatry and Behavioral Sciences and
Department of Dental Health, University of Washington, USA, Casa Pia. Funded
by the National Institute of Dental and Craniofacial Research Cooperative
Agreement U01 DE11894.
2002-04 “Alterações cognitivas nas crises de enxaqueca”. Gil-Gouveia, R., Martins, I.P.
Funded by Sociedade Portuguesa de Cefaleias. (Tecnifar grant)
2002/04 “Anosognosia – Bases biológicas da unidade da consciência”. Martins, I.P.,

Loureiro, C., Ferro, J.M. Funded by Fundação Bial.
2004/07 “Study of emotional perception and affective memory in healthy subjects.

Comparison with different clinical populations” Martins, I.P., Fernandes, S.,
Mendonça, A., Guerreiro, M. Funded by Fundação Bial.
2002/05 Bolsa de Investigação da "Fundação Bial" para "The Neural Structures Involved
in Procedural Memory" Alexandre Castro-Caldas
FCT Fellowships
2001/04 “Adaptação, aferição e validação da bateria de Afasia de Aachen”. Lauterbach,

M. Post-Doc fellowship, Fundação para a Ciência e a Tecnologia (FCT-
SFRH/BPD/5510/2001)
2004/05 “Efeito do declínio cognitivo sobre a memória e percepção emocional: estudo na

população portuguesa”. Fernandes, S., Master’s Degree Fellowship, Fundação
para a Ciência e a Tecnologia (FCT- SFRH/BM/18592/2004)
Clinical Trials
Ongoing “Ensaio clínico aletorizado, duplamente cego, controlado em grupos paralelos,

comparativo de eficácia e segurança com Trifusal vs Placebo em doentes com
alterações cognitivas ligeiras”. Guerreiro, M., Ribeiro, F. Sponsor: J. Uriach &
Cía SA, Tecnifar-Indústria Técnica Farmacêutica AS (ongoing)(N=15).
“Ensaio de 24 semanas, Prospectivo, Randomizado, Multicêntrico, Duplamente

Cego, Controlado com Placebo, de Grupos Paralelos para avaliação da Eficácia,
Tolerabilidade e Segurança de doses 3 e 12 mg/dia Exelon (Rivastigmina) em
Cápsulas, em Doentes com Demência da Doença de Parkinson” Loureiro, C.,
Fernandes, T. Sponsor: Novartis. (N= 14x3 visits)
“Estudo multicêntrico com dupla ocultação, aleatorizado, controlado com

placebo, com a duração de 24 semanas, sobre a eficácia, tolerabilidade e
segurança de Donepezil (Aricept) em doentes com Doença de Parkinson (DP)
com Demência” (Since 2004) Loureiro, C. Sponsor: Quintales.
“Estudo clínico multicêntrico, multinacional, aleatorizado, com dupla ocultação,

paralelo, para avaliar a eficácia e a tolerabilidade do almotriptano 12,5mg versus
zolmitriptano 2,5mg no tratamento agudo da enxaqueca” (2004) Martins, I.P.,
Gil-Gouveia, R. Sponsor: Chiltern International Spain, S.A. (N = 15x2 visits).
“Tratamento precoce da doença de Parkinson idiopática DPI com Piribedil,

agonista dopaminérgico, em monoterapia (adaptação da dos quotidiana de 150 a
300 mg por dia per OS). Estudo crontrolado com Placebo, randomizado, com
grupos paralelos, durante dois anos, em doentes “de novo” com DPI”. Loureiro
C. Sponsor: Servier (N=12x3 visits).
Castro-Caldas, A. (2004) Targeting regions of interest for the study of the illiterate brain.
International Journal of Psychology 39(1):5-17. (Journal IF -)
Cavaco, S., Anderson, S. W., Allen, J. S., Castro-Caldas, A. & Damásio, H. (2004) The scope of
Preserved Procedural Memory in Amnesia. Brain Vol. 127(8):1853-1867. (Journal IF: 7.967)
Coelho, M., Ferreira, J.J., Dias, B., Sampaio, C., Martins, I.P, Castro-Caldas, A. (2004)
Assessment of Time Perception. Effects of aging. Journal of International Neuropsychological
Society 10:332-341. (Journal IF: 2.304)
Gil-Gouveia, R., Wilkinson, P.A., Kaube, H. (2004) Severe hemiplegic migraine attack
precipitatted by fentanyl sedation for esophagogastroscopy. Neurology 63(12):2446.
(Journal IF: 5.678)
Loureiro, C.S., Braga, L.W., Souza, L.N., Filho, G.L., Queiroz, E., Dellatolas, G. (2004) Degree
of illiteracy and phonological and metaphonological skills in schooled adults. Brain and
Language 89(3):499-502. (Journal IF: 1.317)
Clinical Neuropharmacology Group
The Clinical Pharmacology Group aims to contribute to the development of effective and safe
therapeutic interventions for neurodegenerative diseases through the establishment of optimised
methodologies and infrastructures for the assessment of the clinical impact of these measures.
Cristina Sampaio MD, PhD, Auxiliary Professor, FML: 50%
Research Team
Joaquim Ferreira MD - Neurologist HSM, Assistant FML

Mário Miguel Rosa MD - Neurologist HSM, Assistant FML
Miguel Coelho MD - Resident HSM
João Costa MD - Resident HSM
Ema Roque, Management Degree – Technician
Ana Noronha, Bilogy Degree - Technician
Research Areas
Our research activity is organized in three major groups: the Cochrane revision group1 for
movement diseases; the clinical trials unit, whose coordination was attributed to Dr. Joaquim José
Ferreira; and the projects unit, which involves several distinct projects, each one of which has its
own principal investigator. It should be stressed that we have established an ongoing partnership
with the Centre for Clinical Research of the University of Toulouse, directed by Prof. Olivier
Rascol. The research projects that we develop are conducted in cooperation with other
institutions. This collaboration allows for the creation of a bilateral "critical mass" of human
resources and expertise.
The Cochrane Collaboration (http://cochrane.org/) is a non-profit international organization

registered as a charity in the United Kingdom. It comprises doctors, researchers, paramedics,
health services administrators and consumers who joined together with the objective of preparing,
maintaining and disseminating up-to-date systematic revisions of all randomised controlled trials
(RCT) relevant for each one of the therapeutic decisions. When relevant RCTs are not available
for a particular query, the systematic revision will include evidence provided by other sources.
The general objective of the Cochrane Collaboration is to provide the parties involved in
therapeutic decisions (patients, doctors, health care providers) with an accessible, trustworthy and
up-to-date source of information, as it is nor sensible, nor desirable, to expect decision-makers to
have the necessary means and technical knowledge to assess all the evidence relevant for the
decision in question. Presently, The Cochrane Collaboration mobilizes thousands of people in 4
of the 5 Continents. The structure of this organization has become progressively more complex in
order to make its growth more efficient. The basic organizational unit is formed by the Cochrane
Revision Groups (CRG).
In the past 5 years, the group has been moving towards applied research in compliance with the
following guidelines:
1. Establishment of scientific baselines for the development of therapeutic recommendations for

neurodegenerative diseases based on evidence.
a) Definition of methodology principles for clinical trials and systematic revisions.

b) Execution of systematic revisions.
2. Design and conduction of clinical trials of novel therapeutic agents for neurodegenerative
diseases, Parkinson' Disease and focal muscular dystonias, in particular.
3. Definition of the safety profile and establishment of the risk-benefit relationship for drugs of
particular interest for neurodegenerative diseases, for which specific signs of risk have been
identified.
4. Study of the epidemiology of adverse drug reactions (in the context of the scientific research
programme of the Unidade de Farmacovigilância Sul).
Rascol, O., Goetz, C., Koller, W., Poewe, W., Sampaio, C. (2002) Treatment Interventions for
Parkinson’s Disease: An Evidence Based Assessment. Lancet May 4, 359(9317): 1589-98
Sampaio, C. and Ferreira, J. are Members of The Epidemiologic Study of Dystonia in Europe
(ESDE) Collaborative Group (2000) A prevalence study of primary dystonia in eight European
countries. Journal of Neurology 247:787-792. (Times cited: 21) (Journal IF: 2.778)
Lewis, J.A., Jonsson, B., Kreutz, G., Sampaio, C., Zwieten-Boot B. (2002) Placebo controlled
trials and the declaration of Helsinki. Lancet 359:1337-1340
1996/… Editorial Base of the Cochrane Movement Disorders Group: several financing
sources negotiable annually (Fundação MDS, Fundação Grunenthal). In the
context of the Cochrane Collaboration, we coordinate all of the activities of the
Movement Disorders Group and produce top priority systematic revisions.
2001/… Movement Disorders Clinical Trial Unit: Presently, this unit is part of the
Clinical Neurology Research Unit. It exist since 1986 under the designation
"Neuropharmacology Group" and it functions under the context of the Centro de
Neurociências de Lisboa. It is financed by clinical trial contracts.
2002/… Characterization of the incidence, typology and determining factors of adverse

drug reactions in hospitals. Financed by the Pharmacovigilance Unit.
2002/… Study of the placebo effect in the context of clinical trials and implications in
their design. Fundação Bial (Scientific Research Fellowship) 58/98)
2003/… Development of measure instruments usable in clinical trials focused on

Movement Disorders (part of a task force of the International Society for
Movement Disorders).
Neoplastic and preneoplastic skin lesions in Parkinson’s disease patients

Objective: to evaluate whether the risk of melanoma, other neoplastic or preneoplastic skin
lesions is higher in PD patients when compared with an aged-matched population.
Methods: a cross-sectional survey in PD patients and age-matched controls.
Neurological Clinic Research Unit, Institute Molecular Medicine, Lisbon School of Medicine,
Portugal and Dermatology Department, Hospital de Santa Maria, Lisbon, Portugal
Intramuscular Injection of Botulinum Toxin for the Prevention of Wrist and Finger
Spasticity after a Stroke
Exploratory, randomized, double-blind, placebo-controlled trial in stroke patients with a high
probability of developing upper extremity spasticity.
Neurological Clinic Research Unit, Institute Molecular Medicine, Lisbon School of Medicine,
Portugal
International coordination of the project “An open-label study: 10-week evaluation of the
efficacy and safety of levetiracetam (LEV) (oral tablets of 500 mg b.i.d.), up to 3000 mg/day,
in adults with Parkinson’s Disease suffering from L-dopa induced dyskinesia”
Advanced stage Parkinson`s Disease: transversal study on a hospital-based population of

patients with Parkinson`s disease in an advanced stage. Study in collaboration with the
Movement Disorders Unit of Hospital Clinic Barcelona, Spain.
European Study On Multiple System Atrophy (EMSA-SG). Multicentric European study on

multiple system atrophy. Participation of Department of Neurology in the sub-studies of natural
history, DNA study and dysautonomia.
Publications in 2004 International Journals
Sampaio, C., Costa, J., Ferreira, J.J. (2004) Clinical comparability of marketed formulations of
botulinum toxin. Movement Disorders 19 (Suppl. 8):S129-36. (Journal IF in 2003: 2.895)
Coelho, M., Leite, A., Reves, A., Miranda, C., Serra, I., Brandão, T., Albuquerque, L., Freitas, P.
(2004) Mycoplasma pneumoniae causing nervous system lesion and SIADH in the absence of
pneumonia. Clin. Neurol. Neurosurg. 106(2):129-131. (Journal IF: 0.771)
Coelho, M., Marti, M.J., Valls-Solé, J., Pujol, T., Tolosa, E. (2004) Left hemibody myoclonus
due to anomalous right vertebral artery. Movement Disorders 10 (Epub ahead of print). (Journal
IF: 2.895)
Olanow, C.W., Agid, Y., Mizuno, Y., Albanese, A., Bonucelli, U., Damier, P., De Yebenes, J.,
Gershanik, O., Guttman, M., Grandas, F., Hallett, M., Hornykiewicz, O., Jenner, P.,
Katzenschlager, R., Langston, W.J., LeWitt, P., Melamed, E., Mena, M.A., Michel, P.P.,
Mytilineou, C., Obeso, J.A., Poewe, W., Quinn, N., Raisman-Vozari, R., Rajput, A.H., Rascol,
O., Sampaio, C., Stocchi, F. (2004) Levodopa in the treatment of Parkinson's disease: current
controversies. Movement Disorders 2004 19(9):997-1005. Review. PMID: 15372588 [PubMed -
indexed for MEDLINE] (Journal IF: 2.895)
Goetz, C.G., Poewe, W., Rascol, O., Sampaio, C., Stebbins, G.T., Counsell, C., Giladi, N.,
Holloway, R.G., Moore, C.G., Wenning, G.K., Yahr, M.D., Seidl, L. (2004) Movement Disorder
Society Task Force on Rating Scales for Parkinson's Disease. Movement Disorder Society Task
Force report on the Hoehn and Yahr staging scale: status and recommendations. Movement
Disorders 19(9):1020-8. (Journal IF: 2.895)
Wenning, G.K., Tison, F., Seppi, K., Sampaio, C., Diem, A., Yekhlef, F., Ghorayeb, I., Ory, F.,
Galitzky, M., Scaravilli, T., Bozi, M., Colosimo, C., Gilman, S., Shults, C.W., Quinn, N.P.,
Rascol, O., Poewe, W. (2004) Multiple System Atrophy Study Group. Development and
validation of the Unified Multiple System Atrophy Rating Scale (UMSARS).Movement
Disorders 19(12):1391-402. (Journal IF: 2.895)
Murat Emre, M.D., Dag Aarsland, M.D., Ph.D., Alberto Albanese, M.D., E. Jane Byrne,
F.R.C.Psych., M.B., Ch.B., Günther Deuschl, M.D., Peter P. De Deyn, M.D., Ph.D., Franck
Durif, M.D., Ph.D., Jaime Kulisevsky, M.D., Ph.D., Teus van Laar, M.D., Ph.D., Andrew Lees,
M.D., Werner Poewe, M.D., Alain Robillard, M.D., F.R.C.P.C., Mario M. Rosa, M.D., Erik
Wolters, M.D., Ph.D., Peter Quarg, M.Sc., Sibel Tekin, M.D., and Roger Lane, M.D. (2004)
Rivastigmine for Dementia Associated with Parkinson's Disease. N. Engl. J. Med.
9;351(24):2509-18. (Journal IF: 34.833)
IMM – Oncology Programme | 87
Oncology Programme
Nutrition and Metabolism Unit
The Unit is set to promote: 1) Under and Post-Graduate Education in Nutrition and 2) Research in
Clinical Nutrition and Metabolism. In October 2004, a new degree in Dietetics and Nutrition at
the FMUL was initiated under the projection and direction of Unit members.
Nutrition is a broad and expanding area with numerous perspectives, thus investigators pursue
different areas of research in tune with their backgrounds and specific interests. Epidemiology,
nutrition/life-style related risk factors and disease prevention somehow prevail in all research
areas. Interconnections with basic science are further explored, hence the progressive focus on
genetic polymorphisms of inflammatory mediators, e.g. Tumour Necrosis Factor, either as
pathogenic mechanisms of lesion and/or nutritional deterioration, changes of the cellular nuclei
and DNA degradation and its relation to apoptosis in metabolic (alcohol or fat-related) or chronic
diseases (e.g. cancer).
Besides teaching and science, all investigators are free to deliver services to the Hospital or to the
Community.
Maria Ermelinda Camilo, MD, Ph.D. – Auxiliary Professor, FMUL
Pedro Marques-Vidal
Helena Cortez-Pinto
Isabel Monteiro-Grillo
Research Team
Paula Ravasco, RD - Teaching Assistant FMUL, PhD student

Paula Moura Santos - Consultant of Medicine, HSM
Regina Lourenço – Pharmacist, HSM
Isabel Cristina - Pharmacist HSM
Alexandra Sofia Machado Martins, MD
Research Areas
Clinical Nutrition: Principal Investigator Maria E. Camilo

Epidemiology (nutrition, cancer, cardiovascular); Nutrition and cancer : Principal Investigator
Pedro Marques-Vidal
Hepatology; Alcoholic and non-alcoholic steatohepatitis: Principal Investigator Helena Cortez-
Pinto
Oncology, radiotherapy: Principal Investigator Isabel Monteiro-Grillo:
Lourenço, R. (2001) Enteral feeding: Drug / nutrient interaction. Clinical Nutrition 20:187-193.
Mercé Planas, Maria E. Camilo (2002) Artificial nutrition: dilemmas in decision-making. Clinical
Nutrition 2:355-361. (Times cited: 3) (Journal IF: 1.551)
Marques-Vidal, P., Tuomilehto, J. (1997) Hypertension awareness, treatment and control in the
community: is the "rule of halves" still valid? Journal of Human Hypertension 11:213-220.
Marques-Vidal, P., Bongard, V., Ruidavets, J.B., Fauvel, J., Hanaire-Broutin, H., Perret, B, et al.
(2003) Obesity and alcohol modulate the effect of apolipoprotein E polymorphism on lipids and
insulin. Obesity Research 11(10):1200-1206. (Times cited: 1) (Journal IF: 3.409)
Cortez-Pinto, H., Chatham, J., Chacko, V.P., Arnold, C., Rashid, A., Diehl, A.M. (1999)
Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis. Journal of the
American Medical Association (JAMA) 282: 1659-1664. (Times cited: 48) (Journal IF: 2.51)
Cortez-Pinto, H., Camilo, M.E., Baptista, A., Oliveira, A.G., Moura, M.C. (1999) Nonalcoholic
fatty liver - Another feature of the metabolic syndrome? Clinical Nutrition 6:353-358.
Monteiro Grillo, I., L. Gaspar, M. Monteiro Grillo, F. Pires, J.M. Ribeiro da Silva. (2000)
Postoperative Irradiation of Primary or Recurrent Pterygium: Results and sequelae. Int. J.
Radiation Oncology Biol.Phys. 48:865-869. (Times cited: 3) (Journal IF: 3.058)
Ravasco, P., I.Monteiro Grillo, M.E.Camilo (2003) Does nutrition influence quality of life in
cancer patients undergoing radiotherapy? Radiotherapy and Oncology 67:213-220.
Coordinator/Principal Investigator M.E. Camilo
2003/04 EPIDEMIOLOGY, NUTRITION AND CANCER (Head/neck or GI) (no

current funding)
2003/06 CANCER: METABOLIC DYSFUNCTION AND NUTRITION and QoL. (no

current funding)
2003/06 COLORECTAL CANCER AND APOPTOSIS: NUTRITION AND

CELLULAR METABOLISM AS RISK FACTORS. Grant from the Portuguese
Society of Gastroenterology.
2004/07 Fatty Acid Treatment in Pancreatic Cancer: a multicentric randomised double

blind study. Sponsored by Novartis international.
Our group has been pioneer in producing evidence-based data which show the influence of
individualized nutritional counselling in the improvement of cancer patients’ immediate and
short-term outcomes: nutritional status, intake and Quality of Life (QoL); data will be analised in
order to determine whether “Nutrition care throughout RT affect patients’ survival, since
nutritional intake did improve”. In addition, the relative importance of nutrition and cancer
clinical characteristics has been weighted.
We have shown that nutritional status depletion is variable and eventually associated with
circulating concentrations of inflammatory mediators and gene regulated protein transcription
rate. The relative effect of Tumour Necrosis Factor2 polymorphisms, of polymorphisms of
Interleukins 1, 6 or 10, and of tumour growth factors is being evaluated in regard to tumour
incidence and/or progression. Another controversial area is cancer metabolism as evaluated by
Energy Expenditure (EE) measured by indirect calorimetry and how this relates to cytokine
polymorphisms. This study is being conducted in colorectal cancer patients referred for
Radiotherapy (RT) to test the following hypotheses:
1. “Are patients with genetic polymorphisms of inflammatory mediators predisposed for

nutritional deterioration?”;
2. “Is it possible to detect patients at nutritional risk in earlier stages of the disease?”;
3. “Is RT beneficial in tumour reduction and in decreasing the production of inflammatory
mediators?”;
4. “Does RT affect EE by means of reducing local disease and production of inflammatory
mediators, thereby having a beneficial effect on patients’ nutritional status?”
In summary, the research now being conducted in colorectal cancer patients has as major
objectives to explore metabolic or cell to cell pathways underlying the process which leads to
nutritional deterioration beyond the affected nutrition intake; and how much nutrients conveyed
by regular diet or specific nutrients, such as n-3 fatty acids, can modulate patients’ response, the
latter substrate is tested in pancreatic cancer patients.
Principal Investigator Pedro Marques Vidal
2004/06 “Trends in cardiovascular risk factors in the Portuguese population” (no current
funding)
Portugal is characterized by a high level of cardiovascular mortality, namely from stroke. Still,
there are few studies on the prevalence of the main cardiovascular risk factors in the Portuguese
population, and also on their trends. In collaboration with the Observatório Nacional de Saúde
(ONSA) of the Instituto Nacional de Saúde Dr. Ricardo Jorge, we are currently analyzing the data
from the last three Portuguese National Health Surveys, for a total of 120,000 subjects. The
analysis has enabled the submission of several articles, one of which (alcohol consumption
trends) has already been accepted and two others (on obesity) have been re-submitted. The
Principal Investigator and the collaborator from the ONSA have a large expertise in
epidemiological and statistical analysis, and the research team currently has five different
statistical software packages enabling the analysis of virtually any data type. We hope within the
next years to submit several papers on nutrition, smoking, health economics and physical activity.
2004/09 “Nutrition and recurrence from breast cancer: a prospective study” (no current
funding)
Background: breast cancer is the most frequent female cancer in Portugal, accounting for 17% of
all cancer deaths. Further, and albeit adequate treatment, recurrence rates for breast cancer are
relatively high, thus stressing the need for prevention. Several studies have shown that dietary
intake of vegetables and fruit reduces the risk of breast cancer, whereas alcohol consumption,
adult weight gain and high body mass increase the risk. Still, those findings apply mostly to
incident cancer, whereas the impact of diet and body composition on the progression or
recurrence of breast cancer has been much less studied.
Objectives: 1) to assess the dietary intake of patients with diagnosed breast cancer; 2) to correlate
dietary intake and body composition with the severity of the disease; and 3) to assess the impact
of dietary intake and body composition on the recurrence of breast cancer.
Methods: this study has been approved by the ethics committee of the Santa Maria Hospital and
will be conducted at the Radiotherapy department with a minimum sample size of 400 patients
with diagnosed breast cancer less than 6 months. Objective 1) will be attained by assessing
dietary intake within 6 months from diagnosis. A validated food frequency questionnaire and a 24
hour dietary recall with visual aids will be applied; changes in dietary habits will also be assessed.
Dietary intake will be converted to nutrients using specific software. Anthropometric data include
height, weight, waist and body composition (bioelectrical impedance). Data on breast cancer and
other potential confounders will also be collected. Objective 2) will be attained by comparing
dietary intake, dietary patterns and body composition between patients with stage I/II or with
stage III/IV breast cancer, adjusting for total energy intake and other confounders. Objective 3)
will be attained by following the patients for several years. Since all patients are supposed to
come back at least twice per year to the Radiotherapy Department, this follow-up can be
conducted at no extra cost. Whenever a patient fails to come to the follow-up, a letter will be sent
to his GP. Endpoints will include a) deaths from breast cancer; b) local or distant recurrence from
breast cancer, and c) deaths from other causes. Recurrence will be diagnosed upon clinical or
histological data. The analysis will be made in two steps: a) bivariate analysis of the initial dietary
and body composition data between subjects who relapsed and those who didn’t, and b) survival
study using Cox’s model, on energy-adjusted data, dietary patterns and controlling for other
confounders.
Results: the impact of dietary patterns and body composition on breast cancer recurrence will be
assessed. The results will be presented in national/international meetings, and submitted for
publication to leading oncology journals. Relevant information will be made available to the
public and to patients.
2004/09 “Nutrition and recurrence from prostate cancer: a prospective study” (no current
funding)
Background: prostate cancer is the second most frequent male cancer in Portugal, and its
mortality rate has doubled since 1963. Further, and albeit adequate treatment, recurrence rates for
prostate cancer are relatively high, thus stressing the need for prevention. Although a protective
role for selenium, vitamin E, pulses and tomatoes/lycopene and a deleterious role of very high
calcium intake have been suggested, the effect of diet on recurrence of prostate cancer has seldom
been assessed. Indeed, the scarce available data suggest a deleterious effect of saturated fat and a
protective effect of monounsaturated fat, but little is known regarding other foodstuffs and
nutrients.
Objectives: 1) to assess the dietary intake of patients with diagnosed prostate cancer; 2) to
correlate dietary intake with the severity of the disease; and 3) to assess the impact of dietary
intake on the recurrence of prostate cancer.
Methods: this study has been approved by the ethics committee of the Santa Maria Hospital and
will be conducted at the Radiotherapy department with a minimum sample size of 400 patients. A
pilot study has shown a high participation rate and the feasibility of the study. Objective 1) will
be attained by assessing dietary intake within 4 months from diagnosis. A validated food
frequency questionnaire and a 24 hour dietary recall with visual aids will be applied; changes in
dietary habits will also be assessed. Dietary intake will be converted to nutrients using specific
software. Anthropometric data include height, weight, waist and body composition
(skinfolds+bioelectrical impedance). Cancer stage, PSA level, grading and other potential
confounders will also be collected. Objective 2) will be attained by comparing dietary intake
between patients with stage I/II or with stage III/IV prostate cancer, adjusting for total energy
intake and other confounders. Objective 3) will be attained by following the patients for several
years. Since all patients are supposed to come to the Radiotherapy department every four months,
this follow-up can be conducted at no extra cost. Whenever a patient fails to come to the follow-
up, a letter will be sent to his GP or urologist. Endpoints will include a) deaths from prostate
cancer; b) biochemical, local or distant recurrence from prostate cancer, and c) deaths from other
causes. Recurrence will be diagnosed upon biochemical, clinical or histological data. Based on
available prospective data, circa 120 recurrence cases are expected within 3 years. The analysis
will be made in two steps: a) bivariate analysis of the initial dietary data between subjects who
relapsed and those who didn’t, and b) survival study using Cox’s model, on energy-adjusted data
and controlling for other confounders.
Results: will be presented in national/international meetings, and submitted for publication to

leading oncology/urology journals. Relevant information will be made available to the public and
to patients.
Principal Investigator Helena Cortez-Pinto
2003/05 Genetic susceptibility to the hepatic lesion induced by alcohol. Fellowship from
the Portuguese Association for the Study of the Liver (APEF), sponsored by
Schering-Plough Farma in Portugal.
Principal Investigator Isabel Monteiro Grillo
2002/04 “Ensuring quality by involving patients in optimising outcomes and developing

institutional standards in Europe” - EQUIPOISE European Society of
Therapeutic Radiation Oncology (ESTRO)
The European Society for Therapeutic Radiology and Oncology was funded by the EU for a
project on recording providing education, and ameliorating the consequences of treatment
(REACT). A European audit was carried out as part of which to assess the usefulness of current
follow-up practices.
Material and Methods: Over a 4 months period in 15 cancer centers in 10 countries, patients
attending for routine follow-up completed a questionnaire covering their expectations of and
satisfaction with the visit. This was matched with a questionnaire completed by the physician
about the content and usefulness of the consultation. The feasibility of a short toxicity scale
developed by Dische and Saunders was also investigated.Results:In total, 2303 matched
questionaires were analysed. Forty percent of the patients had symptoms or medical problems
related to their disease. In 18% there was a positive finding on clinical examination. In 28%
investigations were undertaken part of departmental routine practice. Tem percent of the
investigations showed na abnormal result. Nynety-nine percent of physicians and 85% of the
patients expressed satisfaction. Using the short toxicity scale rates of recording toxicity could be
increased from 28% to 93%.Conclusion:There is wide variation in follow-up practices among
European centers. There was a law incidence of positive findings clinically or with routine
investigations. A simple scale for recording morbidity has proved easy to use by departments
which have not routinely used one of the standard measures. Further work will attempt to produce
a European guideline for effective follow-up after radiotherapy.
2004/09 “Nutrition and recurrence from breast cancer: a prospective study” (no current
funding)
Background: breast cancer is the most frequent female cancer in Portugal, accounting for 17% of
all cancer deaths. Further, and albeit adequate treatment, recurrence rates for breast cancer are
relatively high, thus stressing the need for prevention. Several studies have shown that dietary
intake of vegetables and fruit reduces the risk of breast cancer, whereas alcohol consumption,
adult weight gain and high body mass increase the risk. Still, those findings apply mostly to
incident cancer, whereas the impact of diet and body composition on the progression or
recurrence of breast cancer has been much less studied.Objectives: 1) to assess the dietary intake
of patients with diagnosed breast cancer; 2) to correlate dietary intake and body composition with
the severity of the disease; and 3) to assess the impact of dietary intake and body composition on
the recurrence of breast cancer.Methods: this study has been approved by the ethics committee of
the Santa Maria Hospital and will be conducted at the Radiotherapy department with a minimum
sample size of 400 patients with diagnosed breast cancer less than 6 months. Objective 1) will be
attained by assessing dietary intake within 6 months from diagnosis. A validated food frequency
questionnaire and a 24 hour dietary recall with visual aids will be applied; changes in dietary
habits will also be assessed. Dietary intake will be converted to nutrients using specific software.
Anthropometric data include height, weight, waist and body composition (bioelectrical
impedance). Data on breast cancer and other potential confounders will also be collected.
Objective 2) will be attained by comparing dietary intake, dietary patterns and body composition
between patients with stage I/II or with stage III/IV breast cancer, adjusting for total energy
intake and other confounders. Objective 3) will be attained by following the patients for several
years. Since all patients are supposed to come back at least twice per year to the Radiotherapy
Department, this follow-up can be conducted at no extra cost. Whenever a patient fails to come to
the follow-up, a letter will be sent to his GP. Endpoints will include a) deaths from breast cancer;
b) local or distant recurrence from breast cancer, and c) deaths from other causes. Recurrence will
be diagnosed upon clinical or histological data. The analysis will be made in two steps: a)
bivariate analysis of the initial dietary and body composition data between subjects who relapsed
and those who didn’t, and b) survival study using Cox’s model, on energy-adjusted data, dietary
patterns and controlling for other confounders.Results: the impact of dietary patterns and body
composition on breast cancer recurrence will be assessed.The results will be presented in
national/international meetings, and submitted for publication to leadingoncology journals.
Relevant information will be made available to the public and to patients.
2004/09 “Nutrition and recurrence from prostate cancer: a prospective study” (no current
funding)
Background: prostate cancer is the second most frequent male cancer in Portugal, and its
mortality rate has doubled since 1963. Further, and albeit adequate treatment, recurrence rates for
prostate cancer are relatively high, thus stressing the need for prevention. Although a protective
role for selenium, vitamin E, pulses and tomatoes/lycopene and a deleterious role of very high
calcium intake have been suggested, the effect of diet on recurrence of prostate cancer has seldom
been assessed. Indeed, the scarce available data suggest a deleterious effect of saturated fat and a
protective effect of monounsaturated fat, but little is known regarding other foodstuffs and
nutrients. Objectives: 1) to assess the dietary intake of patients with diagnosed prostate cancer; 2)
to correlate dietary intake with the severity of the disease; and 3) to assess the impact of dietary
intake on the recurrence of prostate cancer.Methods: this study has been approved by the ethics
committee of the Santa Maria Hospital and will be conducted at the Radiotherapy department
with a minimum sample size of 400 patients. A pilot study has shown a high participation rate
and the feasibility of the study. Objective 1) will be attained by assessing dietary intake within 4
months from diagnosis. A validated food frequency questionnaire and a 24 hour dietary recall
with visual aids will be applied; changes in dietary habits will also be assessed. Dietary intake
will be converted to nutrients using specific software. Anthropometric data include height,
weight, waist and body composition (skinfolds+bioelectrical impedance). Cancer stage, PSA
level, grading and other potential confounders will also be collected. Objective 2) will be attained
by comparing dietary intake between patients with stage I/II or with stage III/IV prostate cancer,
adjusting for total energy intake and other confounders. Objective 3) will be attained by following
the patients for several years. Since all patients are supposed to come to the Radiotherapy
department every four months, this follow-up can be conducted at no extra cost. Whenever a
patient fails to come to the follow-up, a letter will be sent to his GP or urologist. Endpoints will
include a) deaths from prostate cancer; b) biochemical, local or distant recurrence from prostate
cancer, and c) deaths from other causes. Recurrence will be diagnosed upon biochemical, clinical
or histological data. Based on available prospective data, circa 120 recurrence cases are expected
within 3 years. The analysis will be made in two steps: a) bivariate analysis of the initial dietary
data between subjects who relapsed and those who didn’t, and b) survival study using Cox’s
model, on energy-adjusted data and controlling for other confounders.Results: will be presented
in national/international meetings, and submitted for publication to leading oncology/urology
journals. Relevant information will be made available to the public and to patients.
2004/06 “CT Image fusion to evaluate prostate gland motion and volume change between
planning CT and repeated CT four weeks of external radiotherapy treatment” (no
current funding)
The purpose of this study was to evaluate prostate gland maximum displacement (MD) and
volume change between planning CT (plCT) and a repeat CT (rpCT) after four weeks of
treatment on 9 patients (pts). At our department prostate cancer patients are treated in two or three
steps: four-field isocentric technique (PTV1) followed by a six-field coplanar technique (PTV2,
PTV3). The total dose is 74 or 76 Gy depending on tolerance doses of organs at risk
(OAR).Patients were CT scanned with empty bladder and no rectum conditions. Image fusion of
plCT and rpCT, based on 5 anatomical markers placed on the pelvic bones, was performed using
the software IFS v 2.1 (Nucletron/3Dline). Contours of the rpTC were transferred to the plCT and
maximum deviations of the prostate were measured in the AP, Lateral (LAT) and Superior-
Inferior (SI) directions. For each patient, treatment plans designed using the plTC were again
applied to the same plCT (with the contours of the rpCT) in the RTS v. 2.6.2 of Plato (Nucletron)
and DVHs were calculated for CTV and organs at risk (OAR) of both CTs.Four of the 9 patients
had a significant volume reduction of the prostate gland with a medium value of 11,58%, a
maximum value of 15,62% and a minimum value of 6,81%. MDs of prostate gland between plCT
and rpCT occurred in the AP direction with a maximum of 23 mm anterior and a maximum of 21
mm posterior. In 5 patients the prostate moved anteriorly with a medium value of 10,6 mm and in
4 patients the movement was posterior with a medium of 13,3 mm. Concerning movement in the
LAT and SI directions a maximum value of 13 mm to the left was measured in one patient and a
maximum value of 5mm in the superior direction was measured in 4 patients. DVHs showed that
4 patients had a significant reduction of the minimum dose to the CTV with a maximum value of
38,35% and 2 patients had an increase in rectal doses to values outside the tolerance ones. With
this study we concluded that prostate movement is strongly correlated with rectal filling, mainly
in the AP direction. Different rectum conditions between plCT and treatment may lead to
underdosing of the CTV or overdosing of OARs. In order to evaluate with more accuracy prostate
gland motion during radiotherapy we are going to submit more patients in the study. The first part
of the study was presented in an international meeting (ESTRO), and is will be submitted for
publication to leading oncology/urology journals.
Ataman, O., Ann Barrett, S. Davidson, S. Dische, B. Dubray, I. Monteiro Grillo, D. de Haascock,
A.Kramar, C. Haie-Meder, K. Hideghty, J. le Vay, J. Maher, R.P.Muller, C. Regueiro, MI
Saunders, I. Turesson, P. Van Houtte, V. Vitale (2004) Audit of effectiveness of follow-up
clinics after radiotherapy for cancer. A report of the REACT working group of ESTRO.
Radiotherapy and Oncology 72:237-249. (Journal IF: 2.870)
Castro, R, Rivera, I, Ravasco, P, Camilo, ME, Jakobs, C, Blom, HJ, Tavares de Almeida, I.
(2004) 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T and 1298A→C mutations
are associated with DNA hypomethylation”. Journal of Medical Genetics 41: 454-458.
(Journal IF: 6.368)
Cortez-Pinto, H., Camilo, M.E. (2004) Non-alcoholic fatty liver disease/non-alcoholic

steatoheptitis (NALFLD/NASH): diagnosis and clinical course”, In: The Gastroenterologist’s
View of Obesity. Best Practice & Research Clinical Gastroenterology 18(6):1089-1104.
(Journal IF: 0.992)
Cortez-Pinto, H., Marques-Vidal, P., Monteiro, E. (2004) Liver disease-related admissions in

Portugal: clinical and demographic pattern”. European Journal of Gastroenterology and
Hepatology 16 (9): 873-877. (Journal IF: 1.578)
Marques-Vidal, P., Montaye, M., Arvelier, D., Evans, A., Bingham, A., Ruidavets, J.B., et al.
(2004) Alcohol consumption and cardiovascular disease: differential effects in France and
Northern Ireland. The PRIME study. European Journal of Cardiovascular Prevention and
Rehabilitation 11 (4): 336-343. (Journal IF: 0.091)
Marques-Vidal, P., Ruidavets, J.B., Amouyel, P., Ducimetière, P., Arveiler, D., Montaye, M., et
al. (2004) Change in cardiovascular risk factors in France, 1985-1997”. European Journal of
Epidemiology 19 (1):25-32. (Journal IF: 0.972)
Marques Vidal, P., Dias, C.M. (2004) Trends and determinants of alcohol consumption in
Portugal: results from the National Health Surveys 1995-1996 and 1998-1999”. Alcohol and
Alcoholism: Clinical and Experimental Research. (In press). (Journal IF: 1.906)
Monteiro Grillo, I., M. Jorge, M.Ortiz, P. Marques Vidal, P. Ravasco. The effect of locoregional
recurrence on survival and distant metastasis after conservative treatment for invasive breast
carcinoma. Clinical Oncology (In press) (Journal IF: 0.923)
Ravasco, P, Martins, P., Ruivo, A., Camilo, M.E. (2004) Survey on the current practice of
nutritional therapy in Portugal. Clinical Nutrition 23:113-119. (Journal IF: 1.185)
Ravasco, P, Camilo, ME. (2004) Correspondence: reply to a letter on the paper – “Survey on the
current practice of nutritional therapy in Portugal”. Clinical Nutrition 23:438.
(Journal IF: 1.185)
Ravasco, P., Monteiro-Grillo, I., Marques Vidal, P., Camilo, M.E. (2004) Cancer: disease and
nutrition are key determinants of patients’ Quality of Life”. Supportive Care in Cancer 12:246-
252. (Journal IF: 1.367)
Ribeiro, P., Cortez-Pinto, H., Solá, S., Castro, R., Ramalho, R., Baptista, A., Moura, M., Camilo,
M.E., Rodrigues, C. (2004) Hepatocyte Apoptosis, Expression of Death Receptors and Activation
of NF-κB in the Liver of Non-alcoholic and Alcoholic Steatohepatitis Patients. Am. J.
Gastroenterol. 99(9):1708-17. (Journal IF: 4.172)
Molecular Pathobiology Unit
Description/Objectives
The Molecular Pathobiology Research Centre (CIPM) is a Department of The Portuguese

Institute of Oncology Francisco Gentil (IPOFG)/Oncology Regional Centre of Lisbon (CROL,
S.A.). The Director of the Unit is Dr. Sérgio Dias, who is responsible for its global scientific
coordination. The scientific activity of the Unit is centered on the domains of oncobiology and
hematology and its main objectives are the biological and molecular characterization of various
oncological diseases.
The objectives of the Molecular Pathobiology Unit are:
1. To foment and develop basic and applied research to clinical practice in the area of
Oncology.
2. To study the molecular mechanisms of cancer.
3. To promote the genetic diagnosis of the various hereditary cancer syndromes.
4. To implement the development of novel techniques for the molecular monitoring of
cancer after treatment, thus contributing to the detection of minimal residual disease.
5. To study the molecular markers for the early identification of relapse so as to allow for a
more effective management of cancer.
6. To promote the study of novel anti-neoplastic drugs, based on the study of the molecular
mechanisms of the disease.
Coordinator
Sérgio Dias, PhD
Cytogenetics Group
Lúcia Roque, PhD
Endocrinology Group
Valeriano Leite, MD, PhD
Maria João Bugalho, MD, PhD
Gastroenterology Group
Marília Cravo, MD, PhD
Haematology Group
Angiogenesis Group
Sérgio Dias, PhD
Solid Tumors: Hereditary Breast Cancer.

Fátima Vaz, MD
Cytogenetics Group
The main objectives of the cytogenetic group are to identify the chromosomal and gene
abnormalities present in neoplasms; to investigate their correlation with function and expression
in cells, and to determine their association with diagnosis and clinical follow-up.
Lúcia Roque, PhD
Research Team
Maria do Carmo Martins, BSc, PhD

Raquel Rodrigues, PhD Fellowship, FCT
2003/06 C-DNA microarrays as a tool in the diagnosis and monitoring of cancer patients.
(Fundação Gulbenkian).
This is a project embracing all units of CIPM in which we are involved in studying salivary gland
and thyroid tumors.
2004/07 Genetic characterization of Central nervous tumors: Implications in the diagnosis

and clinical follow-up. (Fundação Gulbenkian).
Central nervous system (CNS) tumors are a leading cause of cancer mortality and represent a
major clinical challenge since morphologically and phenotypically similar neoplasms can have
different prognosis and response to treatment.
In this project we want to evaluate brain tumors in order to establish, using (cyto)genetic and
microarray technologies the karyotypic and transcriptional profiles of phenotypically different
brain cancer cells and to determine in way the different profiles correlate with prognosis and
response to treatment.
It is also our aim in realizing this project to overcome the non-existence of consistent genetic
studies on brain tumors in the south region of Portugal.
Endocrinology Group
Research Team (PI - Valeriano Leite)
Branca Cavaco - Investigator, IPOFG

Carla Espadinha - BIC fellowship
Joaquim Vieira - BIC fellowship
Margarida Sancho – Undergraduate student
Isabel Correia – Undergraduate student
Research Team (PI – Maria João Bugalho)
Rita Domingues - Technician, IPOFG/C.R.O.L., SA

Patrícia Costa - BIC Fellowship
2001/03 "Expression of PAX8/PPARγ and RET/PTC oncogenes in benign and malignant

diseases of the thyroid". Liga Portuguesa Contra o Cancro, 2001, 24 months.
PI – Valeriano Leite
2003/05 “Metastasising pathways of papillary and follicular carcinomas of the thyroid”

(in collaboration). Liga Portuguesa Contra o Cancro, 2003, 24 months.
2004/07 "Peroxisome Proliferator-Activated Receptor gamma: a biological modifier of

thyroid carcinomas of follicular origin?". Fundação para a Ciência e a
Tecnologia, 2004, 36 months.
2004/07 "Molecular genetic study of families with hereditary endocrine neoplasia

sindromes". Fundação Calouste Gulbenkian, 2004, 36 months, 30 000 euros.
2004/07 cDNA microarrays for diagnosis and monitoring of patients with different types
of cancer” (in collaboration. Fundação Calouste Gulbenkian, 2004, 36 months.
2003/06 “Estudo genético molecular de famílias com síndromes hereditárias de neoplasias

endócrinas”, Fundação Calouste Gulbenkian.
PI – Maria João Bugalho
Gastroenterology Group
Marília Cravo, MD, PhD – Graduate Hospital Assistant, IPOFG/C.R.O.L., SA
Research Team
Marília Cravo, MD, PhD – Graduate Hospital Assistant, IPOFG/C.R.O.L., SA

Cristina Albuquerque – Internship Researcher, IPOFG/C.R.O.L., SA
Lara Maia – PhD Student, FCT
Célia Baltazar – PhD Student, FCT
Ana Flórido – Master Student
Inês Francisco – Fellowship, CIPM/FCT
Bruno Filipe – Technician, IPOFG/C.R.O.L., SA
Joana Dinis – Fellowship, Calouste Gulbenkian Foundation
Joana Monteiro – Fellowship, FCT
Inês Vitoriano - Fellowship, CIPM/FCT
Sofia Fragoso – Professional Internship
Vera Borrego – Intern
Patrícia Silva - Intern
Research Areas
Molecular characterisation of the various pathways of colon and rectal cancer.

Characterization of genetic alterations in the WNT and Ras/Raf signalling pathways, their
consequences at cellular level and relation with cancer prognosis and therapeutic response
Regulation of APC expression and its role in tumourigenesis
Evaluation of molecular causes underlying the syndromes of multiple adenomas/carcinomas and
hyperplastic polyposis in colon and rectum
Genetic diagnosis of the hereditary syndromes of colon and rectal cancer (FAP and HNPCC)
Genotype-phenotype correlations with particular interest in germinal and somatic mutations.
Smits, R, N. Hofland, W. Edelmann, M. Geugien, S. Jagmohan-Changur, C. Albuquerque, C.

Breukel, R. Kucherlapati, M.F. Kielman, R. Fodde (2000) Somatic APC mutations are selected
upon their capacity to inactivate the β-catenin downregulating activit”. Genes, Chromosomes &
Cancer 29: 229-39. (Times cited: 35) (Journal IF: 4.534)
Cravo, M, A. Afonso, P. Lage, C. Albuquerque, C. Lacerda, P. Fidalgo, P. Chaves, C. Cruz, C.

Nobre-Leitão (2002) Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1
mismatch repair genes: implications for genetic testing. Gut 50: 405-12.
Albuquerque, C., M. Cravo, C. Cruz, P. Lage, P. Chaves, P. Fidalgo, A. Suspiro, C. Nobre Leitão.
(2002) Genetic characterization of patients with multiple colonic polyps. J. Med. Genetics 39:
297-302. (Times cited: 2) (Journal IF: 7.774)
Albuquerque, C., C. Breukel, R. van der Luijt, P. Fidalgo, P. Lage, F.J.M. Slors, C. Nobre Leitão,
R. Fodde, R. Smits (2002) The just-right signaling model: APC somatic mutations are selected
based on a specific level of β-catenin signaling cascade. Human Molecular Genetics 11(13):
1549-1560. (Times cited: 15) (Journal IF: 8.726)
Sieber, O.M., H. Lamlum, M.D. Crabtree, A.J. Rowan, E. Barclay, L. Lipton, S. Hodgson, H.J.W.
Thomas, K. Neale, R.K.S. Phillips, S.M. Farrington, M.G. Dunlop, H.J. Mueller, M.L. Bisgaard,
S. Bulow, P. Fidalgo, C. Albuquerque, M.I. Scarano, W. Bodmer, I.P.M. Tomlinson, K.
Heinimann (2002) Whole-gene APC deletions cause classical familial adenomatous polyposis,
but not attenuated polyposis or “multiple” colorectal adenomas. PNAS 99 (5): 2954-2958.
2004/06 Characterization of the regulatory sequences involved in the regulation of the

expression of the APC ("adenomatous polyposis coli") gene. Fundação para a
Ciência e Tecnologia. Collaboration with the Pathology Department, Josephine
Nefkens Institute, Erasmus University Medical Center.
2004/06 Characterization of regulatory sequences of the adenomatous polyposis coli

(APC) gene: Improvement of genetic diagnosis in hereditary colorectal cancer.
Fundação para a Ciência e Tecnologia. PhD fellowship (Célia Baltazar).
2004/06 Use of the cDNA Microarrays tecnology in the diagnosis and follow-up of
oncological patients. Fundação Calouste Gulbenkian (Collaboration between the
various groups of CIPM).
2004/05 Identification of the molecular events responsible for the development of

multiple colorectal adenomas and for recessive syndrome of colorectal cancer:
involvement of MYH gene. NRS/LPCC -Terry Fox.
2004/05 Genetic alterations in gastric MALT lymphomas: Implications to

lymphomagenesis and treatment response. NRS/LPCC -Terry Fox.
2004/05 c-KIT gene mutations: molecular marker in the assessment of the response of
gastrointestinal stromal tumours to Imatinib therapeutic. Novartis.
2004/07 Apoptosis and inflammatory response in colorectal carcinogenesis: interaction

between the p53 and APC/beta-catenin pathways in prognosis and therapeutic
resistance. Fundação Calouste Gulbenkian. Collaboration between
Gastroenterology group of CIPM and Centro de Patogénese Molecular da
Faculdade de Farmácia da Universidade de Lisboa.
2004/07 Mapping and identification of genes involved in familial thyroid and colorectal
cancers. Fundação Calouste Gulbenkian. Collaboration between the
Endocrinology and Gastroenterology groups of CIPM.
2004/07 In mismatch repair deficiency colorectal cancer are BRAF and KRAS new
prognostic and therapeutic tools? Fundação para a Ciência e Tecnologia.
Collaboration between Gastroenterology group of CIPM and IPATIMUP.
Medical Support to the Community/Diagnostic Proceedings Towards Other Institutions
Genetic diagnosis of colon and rectal cancer hereditary syndromes: Lynch Syndrome (MSH2,
MLH1 and MSH6 genes) and familial adenomatous polyposis (APC and MYH genes).
Microsatellite instability analysis in sporadic colon and rectal tumours.
HematologyUnit

Director of the Hematology Department, IPOFG-CROL,SA
Research Team
Joana Diamond, MSc, PhD- Investigator, IPOFG-CROL,SA

Paula Gameiro, PhD –Biologist, Técnica Superior de Saúde, IPOFG-CROL,SA
Sara Vieira, PhD – Post-Doc Fellowship, FCT
Maria Gomes da Silva, MD,PhD- Consultant in Hematology, IPOFG-CROL,SA
José Luís Passos Coelho, MD, PhD- Consultant in Hematology, IPOFG-CROL, SA
Paulo Lúcio, MD,PhD- IPOFG-CROL,SA
Marta Sebastião- Research fellowship, FCT
Maria João Martins- Research fellowship, FCT
Maria de Jesus Tomé – Technician, IPOFG-CROL,SA
Lara Neto – Técnico Superior, IPOFG-CROL, SA
Elsa Teixeira - Undergraduate Student, Univ. Aveiro
Research Areas
Molecular diagnosis and monitoring of acute and chronic leukaemia.

Assessment of minimal residual disease in acute and chronic leukemia and establishment of its
importance as a prognostic factor.
Molecular diagnosis of lymphoproliferative diseases.
Assessment of minimal residual disease in follicular lymphoma.
Detection of occult breast cancer cells in hematopoietic products and evaluation of its predictive
value for relapse in breast cancer patients.
Hematopoietic differentiation.
BCL6 regulation in non-Hodgkin lymphoma and leukemia.
Jaleco, A.C., Neves, H., Hooijberg, E., Gameiro, P., Clode, N., Haury, M., Domingos, H.,
Parreira, L. (2001) Differential effects of Notch ligands Delta-1 and jagged-1 in human lymphoid
differentiation. J. Exp. Medicine 194:991-1002.
Mortuza, Y.F., Moreira, I., Papaioannou, M., Gameiro, P., Coyle, L.A., Gricks, C.S. Amlot, P.,
Prentice, H.G., Madrigal, A., Hoffbrand, A.V., Foroni, L. (2001) Immunoglobulin heavy-chain
gene rearrangement in adult acute lymphoblastic leukemia reveals preferential usage of JH-
proximal variable gene rearrangements. Blood 97:2716-26.
Gameiro, P., Moreira, I., Yetgin, S., Papaioannou, M., Potter, M.N., Prentice, H.G., Hoffbrand,
A.V., Foroni, L. (2002) PCR and RT-PCR based minimal residual disease (MRD) detection in
long-term follow-up childhood Acute lymphoblastic leukemia (ALL). British Journal of
Haematology 119:685-696. (Times cited: 2) (Journal IF: 3.052)
O’Brien, S., Vieira, S., Connors, S., Chang, J., Capdeville, R., Melo, J.V. (2002) Transient
response to STI571 in a patient with the ETV6-ABL, t(9;12) translocation. Blood 99(9):3465.
van Dongen, J.J.M., Langerak, A.W., Bruggemann, M., Evans, P.A.S., Hummel, M., Lavender,
F.L., Delabesse, E., Davi, F., Schuuring, E., Garcia-Sanz, R., van-Krieken, J.H.J.M., Droese, J.,
Gonzalez, D., Bastard, C., White, H.E., Spaargaren, M., Gonzalez, M., Parreira, A., Smith, J.L.,
Morgan, G.J., Kneba, M., Macintyre, E.A. (2003) Design and standardization of PCR primers and
protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in
suspect lymphoproliferations. Report of the Biomed2 Concerted Action BMH4 CT98-3936.
Leukemia 17:2257-2317. (Times cited: 21) (Journal IF: 5.116)
2005/07 “Estudo de doença mínima residual em linfomas malignos”. Fundação Calouste

Gulbenkian (Proj. nº 69422). Principal investigator: P. Gameiro.
2004/07 “Classificação prognóstica e monitorização de doença mínima residual em

linfomas não Hodgkin”. ROCHE. Principal investigators: P. Gameiro, M. Gomes
da Silva.
2003/05 “Mamaglobina como marcador para avaliação de doença miníma residual em

produtos hemetopoiéticos de doentes com carcinoma da mama – estudo
prospectivo. Liga Portuguesa Contra o cancro. Principal Investigator: JL Passos
Coelho.
2002/05 “Detecção e Quantificação de Doença Mínima residual em Hemopatias

Malignas” Fundação Calouste Gulbenkian (Proj. nº 46975). Principal
Investigators: António Parreira, Joana Diamond, Paula Gameiro.
2004/06 “Detecção e Quantificação de Transcritos BCR-ABL em Doentes com LMC, do

IPOFG-CROL, tratados com GLIVEC.” NOVARTIS. Principal Investigator:
Joana Diamond.
2004/06” O Imatinib no estudo de leucemias Filadélfia positivas”. NOVARTIS.

Principal Investigator: Sara Vieira.
Angiogenesis Group
Sérgio Jerónimo Rodrigues Dias, PhD
Research Team
Cristina Casalou, PhD – Post-Doctoral Fellowship

Susana Constantino, PhD - Post-Doctoral Fellowship (until December 2004)
Margarida Courinha- Student
Ana Paula Elias – PhD Student
Rita Fragoso – PhD student
Cátia Igreja – PhD Student
Manuela Ferreira- PhD Student (until September 2005)
Heissig, B., Hattori, K., Dias, S. et al. (2002) Recruitment of Stem and Progenitor Cells from the
bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109(5):625-37.
Hattori, K., Heissig, B., Wu, Y., Dias, S., et al. (2002) Placental growth factor reconstitutes
hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment.
Nature Medicine 8(8): 841-49. (Times cited: 100) (Journal IF: 28.740)
Bais, C., Van Geelen, A., Eroles, P., Mutlu, A., Chiozzini, C., Dias, S., et al. (2003) Kaposi's
sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells
by activation of the VEGF receptor-2/ KDR. Cancer Cell 3(2):131-43.
Avecilla, S.T., Hattori, K., Heissig, B., Tejada, R., Liao, F., Shido, K., Jin, D.K., Dias, S., et al.
(2004) Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow
vascular niche is required for thrombopoiesis. Nature Medicine 10(1):64-71.
Constantino, S., Rosa Santos and Sérgio Dias (2004) Internal and external autocrine VEGF/KDR
loops regulate survival of subsets of acute leukemia through distinct signaling pathways. Blood
103(10): 3883-9. (Times cited: 0) (Journal IF: 10.120)
2002/05 “The Role of VEGF and its Receptors in Tumour Growth and Angiogenesis”.
In association with Instituto Gulbenkian de Ciência. Financing: Fundação da
Ciência e Tecnologia (FCT).
2003/05 "Metastasising Pathways of Papillary and Follicular Carcinomas of the Thyroid".

In collaboration with Dr. Valeriano Leite (CIPM/Endocrinology). Financing:
Liga Portuguesa Contra o Cancro
2003/05 “Endothelial Progenitors in haematological malignancies”. Financing: Liga

Portuguesa Contra o Cancro.
2004/… “cDNA Microarray Technology in Diagnosis and Monitoring for Oncology

patients”.In collaboration with other PIs at CIPM. Fundação Calouste
Gulbenkian (Portugal).
2004/… “Angiogenesis in Prostate Cancer”. Support from Abbott Pharmaceuticals.
2005/08 “Endothelial Progenitor Biology and Clinical Implications”. Financing:

Crioestaminal.
Solid Tumors: Hereditary Breast Cancer Unit
Our main objective is breast cancer prevention. In Portugal, hereditary breast cancer is poorly
characterized so we have been organizing our work so as to identify and characterize families at
high risk, counsel individuals, analyze the motivations for prevention of these patients, implement
BRCA1 and BRCA2 screening and motivate other health professionals in the management of
BRCA1/2 positive individuals. In 20004, all the work developed before translated in the
identification of several mutations and polymorphisms of the BRCA genes. More than two thirds
of these alterations had not been described yet and one of them is a candidate Portuguese founder
BRCA mutation. This work will allow to characterize Portuguese breast cancer families and
identify strict criteria for genetic screening in our population. The identification of founder
mutations is also important since it may allow genetic screening to become faster and more
effective. We are also interested in the study of the genetic events that explain hereditary cancer
in the absence of BRCA1/2 gene mutations
Fátima Vaz, MD – Medical Oncologist, IPOFG, CROL, SA

Coordinator of the Breast Cancer Family
Risk Multidisciplinary Group
Research Team
Rita Brandão- BIC Fellowship (IMM/BI/10-2004)

Patrícia Machado- Fellow (IPOFG-CROL,SA/ Centro de Emprego)
Joana Eugénio – Estagiária de licenciatura, Curso de Biologia (Ramo Cientifico), Faculdade de
Ciências da Universidade de Lisboa.
Research Areas
Hereditary breast cancer

BRCA1/2 mutations
Role of BRCA polymorphisms in sporadic breast cancer
2002/05 Electronic Registry and optimization of genetic screening of BRCA mutations.

Serviço de Saúde e Desenvolvimento da Fundação Calouste Gulbenkian.- This
project will last until June 2005
2005/06 Study of the Portuguese founder effect of the insertion of an Alu sequence in
exon 3 of the BRCA2 gene- Investigação em Oncologia-Bolsas NRS/LPCC-
Terry Fox para jovens investigadores”
After implementing the difficult screening of BRCA1/2 mutations we ended the screening of the
first 50 high risk families in 2004, 14 of them with male breast cancer probands. These 50
families allowed us to establish the frequency and characteristics of BRCA1/2 in high risk
Portuguese families. Two thirds of our mutations are novel and, although our population is
heterogeneous, founder BRCA mutations may well exist in Portugal. Data is being analyzed to
see if it’s possible to relate some of the different mutations with the aggregation of several cancer
diagnoses (female breast cancer in aggregation either with male breast, gastric cancer or prostate
cancer). This comphreensive analysis is the first to be published in our population and will have a
definite impact in the clinical management of Portuguese hereditary breast cancer families.
We are not yet able to relate geographic origin with the different mutations but after the study of
the next group of individuals that must be possible: these include 70 individuals, male and female
with breast cancer natural from the South and interior North of the country and, interestingly,
several samples from the island of Madeira. Also, as expected, we observed several BRCA1/2
polymorphisms. The relevance of these alterations, either in sporadic and hereditary breast
cancer, will be the subject of future studies.
Avecilla, S.T., Hattori, K., Heissig, B., Tejada, R., Liao, F., Shido, K., Jin, D.K., Dias, S., et al.
(2004) Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow
vascular niche is required for thrombopoiesis. Nature Medicine 10(1):64-71.
(Journal IF: 30.550)
Cavaco, B.M., L. Guerra, K.J. Bradley, D. Carvalho, B. Harding, A. Oliveira, M.A. Santos, L. G.
Sobrinho, R.V. Thakker, V. Leite.(2004) Hyperparathyroidism-jaw tumor syndrome (HPT-JT) in
Romani families from Portugal is due to a founder mutation of the gene encoding
PARAFIBROMIN. Journal of Clinical Endocrinology & Metabolism 89:1747-52.
(Journal IF: 5.873)
Constantino, S., Rosa Santos and Sérgio Dias (2004) Internal and external autocrine VEGF/KDR
loops regulate survival of subsets of acute leukemia through distinct signaling pathways. Blood
103(10): 3883-9. (Journal IF: 10.120)
Lage, P, C. Albuquerque, R. Sousa, M. Cravo, M. Salazar, I. Francisco, L. Maia, I. Claro, A.

Suspiro, P. Rodrigues, H. Raposo, P. Fidalgo, C. Nobre-Leitão (2004) Association of colonic and
endometrial carcinomas in Portuguese families with hereditary nonpolyposis colorectal
carcinoma significantly increases the probability of detecting a pathogenic mutation in mismatch
repair genes, primarily the MSH2 gene. Cancer 101 (1):172-177. (Journal IF: 4.017)
Marques, A., C. Espadinha, A. Catarino, M. João Frias, L. Roque, L. Sobrinho, V. Leite. (2004)
Downregulation of PPARγ in PAX8-PPARγ negative thyroid tumors of follicular origin. British
Journal of Cancer 91:732-738. (Journal IF: 3.894)
Martins C., Cavaco, B., Tonon, G., Kaye, F.J., Soares, J., Fonseca, I. (2004) A study of MECT1-
MAML2 in mucoepidermoid carcinoma and Warthin’s tumor of salivary glands. Journal of
Molecular Diagnostics 6:205-210. (Journal IF: 3.571)
Martins, C., Fonseca, I., Roque, L., Pereira, T., Ribeiro, C., Bullerdiek, J., Soares, J. PLAG1 gene
alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma. A
combined study using chromosome banding, in situ hybridization and immunocytochemistry.
Mod. Pathol. (In press) (Journal IF: 3.323)
Oliveira, C., J.L. Westra, D. Arango, M. Ollikainen, E. Domingo, A. Ferreira, S. Velho, R.

Niessen, K. Lagerstedt, P. Alhopuro, P. Laiho, I. Veiga, M.R. Teixeira, M. Ligtenberg, J.H.
Kleibeuker, R.H. Sijmons, J.T. Plukker, K. Imai, P. Lage, R. Hamelin, C. Albuquerque, S.
Schwartz Jr, A. Lindblom, P. Peltomaki, H. Yamamot, L.A. Aaltonen, R. Seruca, R.M.W. Hofstra
(2004) Distinct patterns of KRAS mutations in colorectal carcinomas according to germline
Mismatch Repair defects and hMLH1 methylation status. Human Molecular Genetics 13(19):
2303-11. (Journal IF: 8.597)
Rodrigues, R.F., Roque, L., Rosa Santos, J., Cid, O., Soares, J. (2004) Chromosomal imbalances
associated with anaplastic transformation of follicular thyroid carcinomas. Br. J. Cancer 90(2):
492-496. (Journal IF: 3.894)
Roque, L., Rodrigues, R., Martins, C., Ribeiro, C., Ribeiro, M.J., Martins, A.G., Oliveira, P.,
Fonseca I. (2004) Comparative genomic hybridization analysis of a pleuropulmonary blastoma.
Cancer Genet Cytogenet 149 (1):58-62. (Journal IF: 1.542)
IMM – Indicators | 110
IMM – Indicators
Publications
International Journals 120
National Jornals 41
Books/Book Chapters
International 20
National 21
Communications in Conferences
International 237
National 189
Organisation of Conferences 40
Thesis
PhD 7
Master’s 11
Diploma 25
Researchers Holding a PhD 96
Institutional Positions 76
Fellows 20
Non PhD Researchers 171
Institutional Positions 62
Fellows/ Other 109
IMM – Detailed R&D Activities | 111
Cell Biology Unit

Books/Book Chapters
Braga, J., Rino, J., Carmo-Fonseca, M. (2004) Photobleaching microscopy reveals the dynamics
of mRNA-binding proteins inside live cell nuclei. In: Progress in Molecular and Subcellular
Biology. P. Jeantur (Ed.): RNA Trafficking and Nuclear Structure Dynamics. Springer-Verlag
Berlin Heidelberg, pp 119-134.
Communications in International Conferences
Braga, J. Introducing three-dimensional information on quantitative fluorescence recovery after

photobleaching experiments. (Poster). 48th Annual Meeting of the Biophysical Society. 14-18
February 2004. Baltimore, Maryland, USA..
Braga, J. Probing molecular mobility: FRAP using 3D information. (Poster). 4th European Light
Microscopy Initiative (ELMI) Meeting, Gothenburg, Sweden. 26-28 May 2004.
Braga, J. Fast intranuclear macromolecular dynamics probed by fluorescence recovery after

photobleaching. (Poster) 3rd Portuguese-Spanish Biophysics Congress. 29 October - 1 November
2004. Lisbon, Portugal.
Calado, P., A. Gomes and M. Carmo-Fonseca. MyoD-dependent gene transcription in a cellular

model of OPMD. (Poster) 9th International Congress of the World Muscle Society, Göteborg,
Sweden, 2004.
Desterro, J.M.P. SUMO-1 localizes to the nucleolus and modifies the editing enzyme ADAR1.
Ninth Annual Meeting of the RNA Society, Madison Wisconsin, 1 – 6 June 2004.
Gama-Carvalho, M., Brodsky, A., Silver, P., Carmo-Fonseca, M. Specific subsets if mRNA
molecules associate with the U2AF65 and PTB splicing factors. RNA Structure and Function: a
joint Biochemical Society/Royal Society of Chemistry Focused Meeting University of Edinburgh,
UK, 4 – 6 December 2004.
Rino, J. Using confocal microscopy photobleaching techniques to visualize dynamics and

interactions of spliceosome components. 4th International Meeting of European Light Microscopy
Initiative (ELMI), 26 – 28 May 2004.
Rino, J. Visualizing dynamics and interactions of spliceosome components using FRAP and
FRET microscopy. 3rd Portuguese-Spanish Biophysics Congress. 29 October - 1 November 2004.
Lisbon, Portugal.
Vivo, M. RNA processing mutations affect the recruitment of RNA polymerase II to the human
beta globin locus. Meeting on Dynamic Organization of Nuclear Function, Cold Spring Harbour
Laboratory, Cold Spring Harbour, New York 29 September - 3 October 2004.
Communications in National Conferences
Calado, P., A. Gomes e M. Carmo-Fonseca. “Modelo de distrofia musclar oculofaríngea –

análise da transcrição dependente de MyoD” (Poster). 8ª Reunião Científica da Sociedade
Portuguesa de Genética Humana, Porto, Portugal, 2004.
Gomes, A.Q. Regulation of alternative splicing during muscle differentiation. Eight Annual
Meeting of the Portuguese Society of Human Genetics. 17-19 November 2004, Porto, Portugal.
Invited Lectures and Seminars
Carmo-Fonseca, M. Sub-nuclear organization of messenger RNA biosynthesis. American Society

for Biochemistry and Molecular Biology Annual Meeting, Boston, MA, 16 June 2004.
Carmo-Fonseca, M. Visualizing mRNA biogenesis. Invited Lecture, Centro de Investigaciones

Biologicas, Madrid, 24 June 2004.
Carmo-Fonseca, M. FRAP and FRET analysis of spliceosome assembly. Simposio sobre Biología
Analítica y Bioimaging en Microscopia Confocal, Centro de Investigaciones Biologicas, Madrid,
25 June 2004.
Carmo-Fonseca, M. Coupling splicing to cell cycle progression. The Werner-Gren Foundation

and the Royal Swedish Academy of Sciences Symposium “The Cell Nucleus”, Kristineberg, 30
June-3 July 2004.
Carmo-Fonseca, M. Imaging transcription and pre-mRNA processing in the mammalian cell

nucleus. 6th EMBL Transcription Meeting. Heidelberg, 28 August - 1 September 2004.
Carmo-Fonseca, M. Splicing factor U2AF35 is required for normal cell cycle progression.
Invited Plenary lecture at ELSO 2004 (European Life Science Organization & International
World Congress of Cell Biology). Nice, 4-8 September 2004.
Carmo-Fonseca, M. Dynamics of spliceosome components in the living cell nucleus. Invited

Plenary Lecture at the Meeting of the Dutch Society of Microscopy, Papendal, 30 November - 1
December 2004.
Desterro, J.M.P. SUMO-1 localizes to the nucleolus and modifies the editing enzyme ADAR1.
Invited Lecture at the XIV Congresso Nacional de Bioquímica, Vilamoura, 3 December 2004.
Gama-Carvalho, M. Nucleocytoplasmic shuttling splicing factors: coordinators of mRNA

metabolism? Invited lecture at the Centro de Investigacion del Cancer, University of Salamanca,
Spain, 11 November 2004.
Organisation of National and International Conferences
Carmo-Fonseca, M. Chaired the Symposium on Sub-nuclear organization. American Society for

Biochemistry and Molecular Biology Annual Meeting, Boston, MA, 16 June 2004.
Carmo-Fonseca, M. Co-Chaired the Symposium on Mechanisms of gene expression. XIV

Congresso Nacional de Bioquímica, Vilamoura, 3 December 2004.
Prizes
The Prize “Estímulo à Ciência 2004” (Fundação para a Ciência e a Tecnologia) was awarded to
M. Carmo-Fonseca.
The Prize “Jovem Investigador 2004” (Sociedade Portuguesa de Genética Humana) was awarded
to A. Gomes.
The Prize “L’Oreal Portugal/Unesco For Women in Science 2004” was awarded to M. Gama-
Carvalho.
Teaching and Public Perception of Science
Braga, J. “FRAP and FLIP” Advanced Light Microscopy in Living Cells”, Instituto Gulbenkian
de Ciência. Oeiras, Portugal, 21-25 June 2004
Braga, J. “The dynamic nucleus”, PGDB doctoral program. Instituto Gulbenkian de Ciência.
Oeiras, Portugal, 29 September 2004
Calado, P. “Genes, genomas e manipulação genética” Neurosciences Master lecture, Faculty of

Medicine, Lisbon.
Calado, P. “Impressões digitais de DNA: quimerismo no transplante de medula óssea e detecção

de clonalidade” - Curso Prático Avançado de Biologia Molecular. Coimbra, 28 October 2004.
Caldeira, S. “Microarrays – Aplicações Médicas” - Curso Prático Avançado de Biologia

Molecular. Coimbra, 04 November 2004.
Carmo-Fonseca, M. A Medicina na era pós-genómica. Ciclo de Colóquios “Despertar para a

Ciência 2004”. Faro, 9 March 2004.

Ciência 2004”. Coimbra, 5 May 2004.

Ciência 2004”. Guarda, 11 May 2004.
Carmo-Fonseca, M. participou na mesa redonda sobre “A utilização de animais em investigação

biomédica” inserida no curso para professores do ensino básico e secundário “Inspirar Ciência”,
Instituto Gulbenkian de Ciência, Oeiras, 13-15 April 2004.
Carvalho, C. Técnicas de hibridação in situ. “Curso de Microscopia Fluorescente e Técnicas de

Marcação”, 9 -13 February 2004. Faculdade de Farmácia da Universidade de Lisboa.
Carvalho, T. “Diagnóstico da tuberculose multirresistente”. Mestrado em doenças infecciosas

emergentes. Faculdade de Medicina de Lisboa, March 2004
Carvalho, T. “Introdução à Biologia Moleculçar e celular”. Licenciatura em Engenharia

Biomédica. Instituto Superior Técnico/Faculdade de Medicina de Lisboa, October 2004
Carvalho, T. Teaching Committee meeting. International First level degree Creation oriented
Biotechnology course. Perugia, June 2004.
Custódio, N. “Quality control of mRNA biogenesis”, PGDB doctoral program. Instituto

Gulbenkian de Ciência. Oeiras, Portugal, 15 October 2004
Custódio, N. “A bioinformática na era pós-genómica” - Curso Prático Avançado de Biologia

Molecular. Coimbra, 28 October 2004.
Desterro, J.M.P. “Farmacogenética e Farmacogenómica – Medicamentos personalizados” - Curso

Prático Avançado de Biologia Molecular. Coimbra, 04 November 2004.
Fleming, E. Supervised the medical student Rui Pedro Costa in the Project Regulação das
proteínas conjugadoras da ubiquitina na resposta a proteínas mal enroladas em mamíferos. 7º
Workshop “Educação pela Ciência” – Projectos de Investigação Científica de alunos, Faculdade
de Medicina de Lisboa, 18 November 2004.
Gama-Carvalho, M. “Fronteiras da Medicina Molecular” e “Tecnologia do DNA recombinante:

proteínas recombinantes e terapia génica” - Curso Prático Avançado de Biologia Molecular.
Coimbra, 28 October 2004.
Gama-Carvalho, M. “mRNA biogenesis module”, PGDB doctoral program. Coordination and

teaching. Instituto Gulbenkian de Ciência. Oeiras, Portugal, 13-19 October 2004
Gama-Carvalho, M. Supervised the medical student Liliana Silva in the Project Papel do U2AF35
no processamento de intrões AG-dependentes in vivo. 7º Workshop “Educação pela Ciência” –
Projectos de Investigação Científica de alunos, Faculdade de Medicina de Lisboa, 18 November
2004.
Gomes, A., “PCR em tempo real: no limite da sensibilidade” – Curso Prático Avançado de
Biologia Molecular. Coimbra 3 November 2004
Rino, J. “FRAP and FLIP” Advanced Light Microscopy in Living Cells”. Instituto Gulbenkian de
Ciência. Oeiras, Portugal, 21-25 June 2004
Rino, J. “mRNA biogenesis – Studying assembled complexes in the cell”, PGDB doctoral
program. Instituto Gulbenkian de Ciência. Oeiras, Portugal, 18 October 2004.
Thesis completed
PhD Thesis
Vitor Hugo Pinto de Sousa (2004) The role of novel Gli-related transcription factors during
mouse development Joint PhD European Molecular Biology Laboratory and Faculdade de
Medicina da Universidade de Lisboa. Supervisor: Mathias Treier; National sponsor: M. Carmo-
Fonseca.
João Eurico Fonseca (2004) Artrite Reumatóide: contribuição da imunohistologia da membrana

sinovial para o diagnóstico, terapêutica e avaliação do prognóstico da doença. Faculdade de
Medicina da Universidade de Lisboa. Supervisors: M. Viana Queiroz and M. Carmo-Fonseca.
Diploma Thesis
Daniel Chaves (2004) “Biogénese de MicroRNAs”. Tese de Licenciatura em Biologia

Microbiana e Genética. Faculdade de Cadencies da Universidade de Lisboa. Supervisor: M.
Carmo-Fonseca.
Hematopoietic Biology Unit
Publications in National Journals
Neves, H. “O futuro da investigação científica em Portugal.” In: 25 de Abril: os Desafios para

Portugal nos Próximos 30 Anos. Eds: Presidência do Conselho de Ministros. Comissão das
Comemorações dos 30 anos do 25 de Abril. Imprensa Nacional-Casa da Moeda, páginas: 113-
121, 2004.
Batista, A., J.T. Barata, L.F. Costa, S.E. Sallan, N. Carlesso, L.M. Nadler, A.A. Cardoso. “mTOR
as Therapeutic Target for T-Cell Leukemia: Synergism with Conventional Cytotoxic Drugs and
Signaling Inhibitors”. 46th Annual Meeting of the American Society of Hematology. San Diego,
California, United States, 4-7 December 2004.
Brandão, J.G., J.T. Barata, R. Nunes, L.M. Nadler, A.A. Cardoso. “Crosstalk between Breast
Cancer Cells and Bone Marrow Endothelium Require the Engagement of PI3K/Akt Signaling”.
46th Annual Meeting of the American Society of Hematology. San Diego, California, United
States, 4-7 December 2004. (poster)
Neves, H., Floor Weerkamp, Brigitta A.E. Naber, Paula Gameiro, Jörg D. Becker, Paulo Lúcio,
Nuno Clode, Jacques J.M. van Dongen, Frank J.T. Staal, Leonor Parreira. “Differential roles of
notch ligands Delta1 and Jagged1 in human hematopoietic progenitor cell differentiation”. 2nd
Annual Meeting of the International Society for Stem Cell Research. Boston, United States, 10-13
June, 2004.
Nuno Clode, Jacques J.M. van Dongen, Frank J.T. Staal, Leonor Parreira. “Differential effects of
notch ligands Delta1 and Jagged1 in human myelopoiesis”. 33rd Annual Meeting of the
International Society for Experimental Hematology. New Orleans, United States, 17-20 July,
2004.
Delta1 and Jagged1 in early human myelopoiesis: Correlation with distinct gene-expression
profiles in CD34+ cells”. 46th Annual Meeting of the American Society of Hematology. San
Diego, California, United States, 4-7 December 2004.
Barata, J.T., A. Silva, A.A. Cardoso. “Murine IL-7 mimics the functional and molecular effects of
human IL-7 on normal and malignant human T cells”. XIV National Biochemistry Meeting of the
Portuguese Biochemical Society, Vilamoura, Portugal, 2-7 December 2004.
notch ligands Delta1 and Jagged1 in human myelopoiesis”. Instituto de Medicina Molecular,
Faculdade de Medicina de Lisboa, Portugal, 31 May 2004.
Neves,H. “Modelos experimentais no estudo da hematopoiese”. Reunião anual da Sociedade

Portuguesa de Hematologia. Carvoeiro, Portugal, 11-13 November 2004.
Barata, J.T. Invited seminar Interleukin-7-mediated signaling in the biology of T-cell acute
lymphoblastic leukemia, IGC (Instituto Gulbenkian de Ciência), Oeiras, Portugal, 20 February
2004.
Barata, J.T. Invited seminar Interleukin-7-mediated signaling in the biology of T-cell acute
lymphoblastic leukemia, IBMC (Instituto de Biologia Molecular e Celular), University of Porto,
Portugal, 7 June 2004.
Barata, J.T. Chair of the session on Immunology (Friday, 17th), Joint Meeting of Graduate
Programmes on Biosciences, Hotel Vila Galé, Porto, Portugal, 16th-20th December 2004.
Prizes
Silva, A. (Tumor Biology Group) Prize “Programa Gulbenkian de Estímulo à Investigação

2004” (Fundação Calouste Gulbenkian).
Barata, J.T. “Tumors of the Immune System: Proliferation, Differentiation and Signal
Transduction.” Mestrado em Imunologia Clínica, Faculdade de Ciências Médicas, Universidade
da Beira Interior, Covilhã, Portugal.
Parreira, L. Células Estaminais. Enigmas e Promessas. Fundação Calouste Gulbenkian 6 de

Outubro de 2004.
Neves, H. “O futuro da investigação científica em Portugal.” Colóquio de Encerramento das

Comemorações Nacionais dos 30 anos do 25 de Abril. Porto, Portugal, 16 December 2004.
Chromatin Biology Unit
Bozhenok, L., Poot, R.A., van den Berg, D.L.C., Steffensen, S., Ferreira, F., Grimaldi, M.,
Ferreira, J. and Varga-Weisz, P. WSTF in transcription- and replication-coupled chromatin
remodeling.(Poster) 6th EMBL Transcription Meeting, 28 August - September 2004, EMBL,
Heidelberg, Germany.
Steffensen, S., Ferreira, F., Rino, J., Braga, J., Agostinho, M. and Ferreira, J. Localization and
dynamics of cellular topoisomerases at sites of adenoviral replication and transcription. (Poster).
Dynamic Organization of Nuclear Function. 29 September - 3 October 2004, Cold Spring Harbor,
N.Y., USA.
Agostinho, M., Rino, J., Braga, J., Ferreira, F., Steffensen, S. and Ferreira, J. Human
topoisomerase IIa: targeting to subchromosomal sites of activity during interphase and mitosis.
XIV Congresso Nacional de Bioquímica, 2-4 December 2004, Vilamoura, Portugal.
Ferreira, F., Steffensen, S., Braga, J., Rino, J., Agostinho, M. and Ferreira, J. Importância das
topoisomerases I e IIa na progressão da infecção adenoviral em células de mamífero. (Oral
Communication). XXXIX Reunião Anual da Sociedade Portuguesa de Microscopia Electrónica e
Biologia Celular, 4-6 November 2004, Aveiro, Portugal.
Ferreira, J. Cell and Molecular Biology module, Masters Course in Biophysics; Faculty of
Science, Lisbon, Portugal, 1-29 December 2004.
Developmental Biology Unit
Afonso, C. Cell fate and cell polarity in the chick embryonic neuroepithelium, EMBO Workshop
on Epithelial Polarity in Development and Disease, 27-31 March 2004, Carry-le-Rouet
Afonso, C. Cell fate and cell polarity in the chick embryonic neuroepithelium, The Cell in
Development, III Annual Symposium, Centre for Genomic Regulation, 14-17 October 2004,
Barcelona, Spain.
Fior, R. A cascade of HES genes regulate neurogenesis in the chick embryo, Joint BSDB/Gentical
Society Meeting, 14-17 March 2004, Warwick, U.K.
Fior, R. A cascade of HES genes regulate neurogenesis in the chick embryo, The Cell in
Development, III Annual Symposium, Centre for Genomic Regulation, 14-17 October 2004,
Barcelona, Spain.
Lopes, S., Two Delta genes involved in retina neurogenesis, The Cell in Development, III Annual
Symposium, Centre for Genomic Regulation, 14-17 October 2004, Barcelona, Spain.
Henrique, D. The role of Notch signalling during Neural Development. Jornadas de Genética,
I.T.Q.B., Oeiras, 05 February 2004.
Henrique, D. Cell polarity during neural development. Centre de Biologie du Développement,

Université Paul Sabatier, Toulouse, 26 February 2004.
Henrique, D. Cell polarity during neural development. 5 May 2004, Universidad Pompeu Fabra,
Barcelona, Spain.
Henrique, D. Notch cycles, HES genes and neurogenesis. 25 November 2004, Instituto Alberto
Sols, Univ. Autónoma, Madrid, Spain.
Prizes
Rita Fior – Young Geneticist of the year 2004, Genetics Society, U.K.
Henrique, D. “Developmental Biology”, PhD programme in Experimental Biology and

Biomedicine. Coordination and teaching. University of Coimbra, 8-12 November 2004.
Thesis Completed
Diploma Thesis
Susana Rocha (2004) “RNAi e sinalização Notch”. Tese de Licenciatura em Bioquímica.

Faculdade de Ciências da Universidade de Lisboa. Supervisor: Domingos Henrique
Manuel Baptista (2004) “Estudos da Polaridade em Neurónios derivados de células estaminais

embrionárias”. Tese de Licenciatura em Bioquímica, Faculdade de Ciências da Universidade de
Lisboa. Supervisor: Domingos Henrique
Ana Faro (2004) “Polaridade celular”. Tese de Licenciatura em Biologia Microbiana e Genética.
Faculdade de Ciências da Universidade de Lisboa. Supervisor: Domingos Henrique
Bernardo Lopes (2004) “Caracterização da expressão de genes envolvidos na via de sinalização

dos canabinóides em embriões de galinha”. Tese de Licenciatura em Biologia Aplicada,
Universidade do Minho. Supervisor: Domingos Henrique
Reproduction Biology Unit
Cidadão, A.J. (2004) IVIMEDS: Uma breve reflexão sobre o papel das novas tecnologias de
educação no panorama actual da FML. Revista da Faculdade de Medicina de Lisboa, Série III,
Vol.9, Nº3, 183-186.
Plancha, C.E., P. Navarro-Costa, S.C. Correia, A. Gouveia-Oliveira, F. Negreiro, S. Jorge, A.J.

Cidadão, M.J. Carvalho (2004) Effects of mouse ovarian tissue cryopreservation on granulosa
cell-oocyte interaction. (Oral). 37th Annual Meeting of the Society for the Study of
Reproduction. 1-4 August 2004. Vancouver, Canada.
Plancha, C.E., P. Navarro-Costa, S.C. Correia, A. Gouveia-Oliveira, F. Negreiro, S. Jorge, A.J.

Cidadão, M.J. Carvalho (2004) Effects of whole-ovary cryopreservation on granulosa cell-oocyte
interaction. (Poster). XVth OVARIAN WORKSHOP: The ovary - signalling mechanisms
regulating development and dysfunction. 29-31 July 2004. Vancouver, Canada.
Rodrigues, P., C.E. Plancha, D.F. Albertini (2004) Effect of FSH on the expression of polarity in
granulosa cells of pre-antral mouse ovarian follicles. (Poster). 37th Annual Meeting of the
Society for the Study of Reproduction. 1-4 August 2004. Vancouver, Canada.
Sanfins, A., C.E. Plancha, E.W. Overstrom, D.F. Albertini (2004) The M-II meiotic spindle
phenotype in vivo is determined early in meiotic progression. (Poster). 37th Annual Meeting of
the Society for the Study of Reproduction. 1-4 August 2004. Vancouver, Canada.
Cidadão, A.J. (2004) IVIMEDS: uma solução de blended-learning integrada no projecto FML-
Digital. Conferência eLES’04 - eLearning no Ensino Superior, Universidade de Aveiro, 27-29
Out.
Rato, M.L., P. Navarro-Costa, S.C. Correia, S. Jorge, P.M. Vidal, M.J. Carvalho, C.E. Plancha
(2004) Effect of cytoskeleton depolymerization on immature oocyte cryopreservation. (Oral) 2º
Congresso Nacional da Sociedade Portuguesa de Medicina da Reprodução. October 2004.
Espinho, Portugal.
Rodrigues, P., C.E. Plancha, D.F. Albertini (2004) Effect of FSH on the expression of polarity in
granulosa cells of pre-antral mouse follicles. (Poster). 2º Congresso Nacional da Sociedade
Portuguesa de Medicina da Reprodução. October 2004. Espinho, Portugal. (prémio de melhor
poster científico)
Sanfins, A., C.E. Plancha, E.W. Overstrom, D.F. Albertini (2004) Characterizing the first stages
of oocyte maturation between mouse oocytes matured in vivo and in vitro. (Oral) 2º Congresso
Nacional da Sociedade Portuguesa de Medicina da Reprodução. October 2004. Espinho, Portugal.
Albertini, D.F., C.E. Plancha (2004) Somatic-germinal cell cross talk in the ovary. Serono
Symposia International conference “From oocyte to embryo: a pathway to life". 24-26 September
2004. Stresa, Italy.
Plancha, C.E. (2004) Síndrome de Turner e Reprodução. Painel de Discussão “Síndrome de

Turner na idade adulta”, 55ª Reunião Anula da Sociedade Portuguesa de Endocrinologia /
Diabetes e Metabolismo. January 2004. Espinho, Portugal.
Plancha, C.E. (2004) In vivo and in vitro oocyte maturation. 3ª Reunião Internacional do
Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina do Porto – Hospital de S.
João. May 2004. Espinho, Portugal.
Plancha, C.E., P. Rodrigues, A. Sanfins, D.F. Albertini (2004) Cell polarity during
folliculogenesis and oogenesis. Serono Symposia International conference “From oocyte to
embryo: a pathway to life". 24-26 September 2004. Stresa, Italy.
Plancha, C.E., S.C. Correia (2004) Oogénese. O oocito ao microscópio. Aspectos normais e
anormais. 2º Congresso Nacional da Sociedade Portuguesa de Medicina da Reprodução. October
2004. Espinho, Portugal.
Plancha, C.E., A. Sanfins, P. Rodrigues, P. Navarro-Costa, M. Rato, A.J. Cidadão (2004) In vitro
maturation of oocytes. 2º Congresso Nacional da Sociedade Portuguesa de Medicina da
Reprodução. October 2004. Espinho, Portugal.
Cidadão, A.J. (2004) 23rd European Conference on Microcirculation, Lisbon, Sept 8-10. Local
organizing committee. European Society for Microcirculation / Faculdade de Medicina de Lisboa
Prizes
Best Poster Award – Basic Sciences 2004 (Portuguese Society of Reproduction Medicine) P
Rodrigues, CE Plancha, DF Albertini (2004) Effect of FSH on the expression of polarity in
granulosa cells of pre-antral mouse follicles. (Poster). 2º Congresso Nacional da Sociedade
Portuguesa de Medicina da Reprodução. October 2004. Espinho, Portugal.
Cidadão, A.J. (2004) Módulo de Biologia Celular e Molecular. Mestrado em Psicogerontologia,

Faculdade de Medicina de Lisboa.
Cidadão, A.J. (2004) “Investigação Fundamental em Saúde” Pós-Graduação de Comunicação em

Saúde Investigação em Saúde, Universidade Lusíada de Lisboa.
Plancha, C.E. “Técnicas de Reprodução Assistida no Humano”. Disciplina Opcional do Curso de

Mestrado em Biologia do Desenvolvimento, Universidade Lusófona. Lisboa, February 2004.
Plancha, C.E. “Inovações técnicas da Reprodução Humana e problemática decorrente”. Mestrado

em Sexualidade Humana, FML, Lisboa, May 2004.
Plancha, C.E. “Aparelho Reprodutor e Reprodução Medicamente Assistida”. Disciplina opcional

de Fertilização e Modelos de Infertilidade, 4º ano da Licenciatura em Biologia, Universidade
Lusófona. Lisboa, June 2004.
Plancha, C.E. “Media for oocyte In Vitro Maturation” Co-moderador online, com Arne Sunde, na
Internet Conference promovida pela organização Alpha-Scientists. October 2004. Internet:
http://www.alphascientists.com
Plancha, C.E. “O citosqueleto em neurónios”. Mestrado em Neurociências, FML, Lisboa,

November 2004.
Plancha, C.E. “Histologia do Aparelho Respiratório”. Licenciatura em Eng. Biomédica. FML,

Lisboa, November 2004.
Plancha, C.E. “Génese e Desenvolvimento”. 8º Seminário Nacional do Conselho Nacional de

Ética para as Ciências da Vida: Da célula ao embrião. Fundação Calouste Gulbenkian, Lisboa,
November 2004.
Plancha, C.E. “Histologia do Aparelho Reprodutor”. Licenciatura em Eng. Biomédica. FML,

Lisboa, December 2004.
Sanfins, A. Teaching assistance in the course "Frontiers in Reproduction". Marine Biological

Laboratory. Woods Hole, MA, USA. Head: DF Albertini. June 2004.
Thesis Completed
PhD Thesis
José Eduardo Ferreira de Oliveira Gomes (2004) “Asymetric Cell Division: a genetic analysis of
cell fate patterning and mitotic spindle orientation in C. elegans early embryos”. Doutoramento
em Ciências Biomédicas pela Faculdade de Medicina da Universidade de Lisboa. Supervisor:
Prof. Bruce Bowerman (Institute of Molecular Biology, University of Oregon, Oregon, USA);
National sponsor: C.E. Plancha.
Diploma Thesis
Ana Mafalda Leal Rato (2004) “Efeito da despolimerização do citosqueleto na criopreservação de

oocitos imaturos de mamífero”. Tese de Licenciatura em Biologia. Faculdade de Ciências da
Universidade de Lisboa. Supervisor: C.E. Plancha.
Vascular Pathobiology Unit
Martin Martins, J., Vale, S. (2004) Endocrinologia hospitalar – esboço de análise.

Endocrinologia. Metabolismo e Nutrição, 13:81-104.
Martins e Silva, J., Saldanha, C. (2004) Breve historial sobre a criação e evolução de uma
associação científica para o estudo da hemorreologia e da microcirculação em Portugal. RFML 9:
225-229.
Pereira Albino, J., Mesquita, R., Saldanha, C. (2004) Contribuição para o estudo epidemiológico
da doença venosa crónica em Portugal. Boletim da SPHM 19(1): 23-33.
Books/Book Chapters
Martins e Silva, J. (2004) Lições de Química Fisiológica. Edição Fac-simile, Vol. I, II, III, IV, V,
Lisboa (ano lectivo 1972-1973).
Martins e Silva, J. (2004) Da circulação sanguínea à descoberta de novos caminhos. In:

Circulação, Valente Alves, M., Barbosa, A. (Ed.). Faculdade de Medicina de Lisboa, Lisboa, pp
11-13.
Martins e Silva, J. (2004) Viscosidade sanguínea. Antecedentes, característica e importância. In:

Circulação, Valente Alves, M., Barbosa, A. (Ed.). Faculdade de Medicina de Lisboa, Lisboa, pp
179-197.
Saldanha, C. (2004) Agregação eritrocitária. In: Circulação, Valente Alves, M., Barbosa, A.
(Ed.). Faculdade de Medicina de Lisboa, Lisboa, pp 73-79.
Carvalho, F.A., Calado, A, Graça, L.M., Martins-Silva, J., Saldanha, C. Biochemical

Characterization of acetylcholinesterase in human umbilical vein endothelial cell membranes.
(Poster selected for oral presentation). VIII International Meeting on Cholinesterases, 26-30
September 2004, Perugia, Italy. Communication content published in (2004) Boletim da SPHM
19 (3):17-21.
Carvalho, F.A., Martins-Silva, J., Saldanha, C. The study of velnacrine maleate effects on
endothelial cell second messengers. (Poster). 23rd European Conference on Microcirculation, 8-11
September 2004, Lisboa, Portugal. Communication content published in (2004) Boletim da
SPHM 19 (3):52-55.
Carvalho, F.A., Martins-Silva, J., Saldanha, C. The study of velnacrine maleate effects on
erythrocytes second messengers. (Poster). 23rd European Conference on Microcirculation, 8-11
September 2004, Lisboa, Portugal. Communication content published in (2004) Boletim da
SPHM 19 (3):55-58.
Carvalho, F.A., Soares, D., Maria, A.V., Guerra, J., Martins Prata, M., Martins-Silva, J.,
Saldanha, C. Study nitric oxide production on healthy versus sick persons. (Poster). 23rd European
Conference on Microcirculation, 8-11 September 2004, Lisboa, Portugal. Communication content
published in (2004) Boletim da SPHM 19 (3): 59-62.
Gonçalves, S., Santos, N.C., Martins e Silva, J., Saldanha, C. Conformational changes during
fibrinogen-ligand binding followed by fluorescence spectroscopy. (Poster). 23rd European
Conference on Microcirculation, 8-11 September 2004, Lisboa, Portugal. Abstract published in
(2004) J. Vasc. Res., 41 (S2), 25. Communication content published in (2004) Boletim SPHM 19
(3):41-44.
Gonçalves, S., Silva, A.S., Branco, C., Saldanha, C., Martins e Silva, J. Phytosterols in milk
effects on plasma cholesterol concentrations: experimental evidence in portuguese healthy
subjects. (Poster). 23rd European Conference on Microcirculation, 8-11 September 2004, Lisboa,
Portugal. Abstract published in (2004) J. Vasc. Res. 41(S2):48. Communication content
published in (2004) Boletim SPHM, 19(3):36-37.
Gonçalves, S., Silva, A.S., Saldanha, C., Martins e Silva, J., Maria, A.V. Phytosterols in milk as a
depressor of plasma cholesterol levels: experimental evidence in hypercholesterolemic subjects.
(Poster). 23rd European Conference on Microcirculation, 8-11 September 2004, Lisboa, Portugal.
Abstract published in (2004) J. Vasc. Res. 41 (S2):48. Communication content published in
(2004) Boletim SPHM 19(3):38-39.
Gonçalves, S., Santos, N.C., Martins-Silva, J., Saldanha, C. Fluorescence spectroscopy

quenching study of fibrinogen-ligand binding. (Poster). 3rd Portuguese-Spanish Biophysics
Congress, 29 October – 1 November 2004, Lisboa, Portugal. Communication content published
in (2004) Boletim SPHM 19 (4):29-33.
Martin Martins, J., Vale, S., Carrilho, B., Saldanha, C., Martins e Silva, J. Adrenal
steroidogenesis in inappropriate high blood pressure. (Oral communication) XIV European
Meeting in Hhypertension. 13-17 June 2004, Paris, France. Communication content published in
(2004) Boletim da SPHM 19(2):27-29.
Martin Martins, J, Vale, S., Carrilho, B., Saldanha, C., Martins e Silva, J. Plasma cortcotropin
releasing hormone (CRIT) and I-endorphin in relation to body fat eating behaviour. (Poster) 12th
International congress of endocrinology, 31 August - 4 Setember 2004, Lisbon, Portugal.
Communication content published in (2004) Boletim da SPHM 19(4):40.
Pereira Albino, J., Saldanha, C., Martins e Silva, J. Acetylcholinesterase (AChE), A new marker
of chronic venous diseases. (Poster) 23rd European Conference on Microcirculation, 8-11
September 2004, Lisboa, Portugal.
Rosário, H.S., Saldanha, C., Martins-Silva, J. Intraluminal pancreatic trypsin increases

neutrophil infiltration into the intestinal wall during acute ischemia-reperfusion. (Poster) 23rd
European Conference on Microcirculation, 8-11 September 2004, Lisboa, Portugal.
Rosário, H.S., Waldo, S.W., Schmid-Schönbein, G.W. Trypsin-induced neutrophil degranulation

and matrix metalloproteinase activation: a time-frame analysis. (Poster) 23rd European
Conference on Microcirculation, 8-11 September 2004, Lisboa, Portugal.
Saldanha, C. No as a marker of endothelial dysfunction: clinical correlations. (Oral

communication) 23rd European Conference on Microcirculation, 8-11 September 2004, Lisboa,
Portugal
Santos, N.C., Antunes, F., Doroana, M., Duarte, N., Tavares, L., Saldanha, C., Martins-Silva, J.
Alteration of lymphocyte and erythrocyte membrane properties in HIV-1 infected patients. (Oral
communication). 3rd Portuguese-Spanish Biophysics Congress, 29 October – 1 November 2004,
Lisboa, Portugal. Communication content published in (2004) Boletim SPHM 19(4):34-38.
Santos, N.C., Martins e Silva, J., Saldanha, C. Gramicidin D, dithiothreitol and cytochalasin B
effects on erythrocyte exovesiculation. (Poster). 23rd European Conference on Microcirculation, 8-
11 September 2004, Lisboa, Portugal. Abstract published in (2004) J. Vasc. Res. 41(S2):26.
Communication content published in (2004) Boletim SPHM 19(3):62-67.
Silva, A.S., Martins e Silva, J., Saldanha, C. Effects of phytosterols supplied in half-fat and low-
fat milk, in the serum cholesterol concentrations in rats. (Poster) 23rd European Conference on
Microcirculation, 8-11 September 2004, Lisboa, Portugal. Abstract published in (2004) J. Vasc.
Res. 41(S2):49. Communication content published in (2004) Boletim SPHM 19(3):48-51.
Silva, A.S., Saldanha, C., Martins e Silva, J. Effects of velnacrine maleate in the leukocyte-
endothelial cell interactions in rat cremaster microcirculatory network. (Poster) 23rd European
Conference on Microcirculation, 8-11 September 2004, Lisboa, Portugal. Abstract published in
(2004) J. Vasc. Res. 41(S2):26. Communication content published in (2004) Boletim SPHM 19
(3):44-48.
Silva, A.S., Saldanha, C., Martins e Silva, J. Effects of the acetylcholinesterase inhibitor,
velnacrine maleate in the leukocyte-endothelial cell interactions (Poster). VIIIth International
Meeting on Cholinesterases, 26-30 September 2004, Perugia, Italy. Communication content
published in (2004) Boletim da SPHM 19(3):22-27.
Vale, S., Martin Martins, J., Carrilho, B., Saldanha, C., Martins e Silva, J. Pulse wave velocity
(PWV) before major vascular events. Statistical relevant biologic factors (Oral communication)
XIV European Meeting in Hypertension, 13-17 June 2004, Paris, France. Communication content
published in (2004) Boletim da SPHM 19(2):30-32.
Vale, S., Martin Martins, J., Carrilho, B., Saldanha, C., Martins e Silva, J. Behavioural correlates
of dehidroepiandrosterone-sulphate (DHEAS). (Poster) 12th International congress of
endocrinology, 31 August - 4 Setember 2004, Lisbon, Portugal. Communication content
published in (2004) Boletim da SPHM 19(4):39.
Veiga, A.S., Henriques, S.T., Santos, N.C., Castanho, M.A.R.B. HIV-1 fusion inhibitor
enfuvirtide mode of action at the molecular level. Fluorescence spectroscopy reveals
biomembranes role. Congress on Peptide-Membrane Interactions, 9-12 October 2004, Namur,
Belgium.
Gonçalves, S., Silva, A.S. Silva, Saldanha, C., Martins e Silva, J., Maria, A.V. Estudo do efeito
do leite enriquecido em fitoesteróis nos níveis de colesterol, agregação eritrocitária e
viscosidade plasmática. (Oral communication). XII Congresso Português de Aterosclerose, 14-16
October 2004, Almancil, Portugal. Communication content published in (2004) Boletim da
SPHM 19(1):23.
Martin Martins, J., Vale, S., Saldanha, S., Martins e Silva, J. Plasma CRH changes during the
feeling of induced emotions. (Oral communication) 55ª Reunião annual da Sociedade Portuguesa
de Endocrinologia, 23-25 January 2004, Granja, Portugal. Communication content published in
(2004) Boletim da SPHM 19(1):34.
Silva, A.S., Branco, C., Saldanha, C., Martins e Silva, J. Estudo do efeito da ingestão de leite
enriquecido com fitoesteróis nos níveis de colesterol e viscosidade plasmática. (Oral
communication). XII Congresso Português de Aterosclerose, 14-16 October 2004, Almancil,
Portugal. Communication content published in (2004) Boletim da SPHM 19(4):19.
Saldanha, C., Pacheco, T., Silva, A.S., Martins e Silva, J. Biochemical characteristic associated
to rabbit telepathy (Poster) 5º Simpósio da Fundação Bial, Aquém e Além do Cérebro, Behind
and Beyond the Brain, Porto 31 March - 3 April, 2004.
Vale, S., Martin Martins, J., Carrilho, B., Saldanha, S., Martins e Silva, J. Plasma CRH and β-
endorphin in depressed patients before and after short term treatment with serotonin re-uptake
inhibitor. (Oral communication) 55ª Reunião annual da Sociedade Portuguesa de Endocrinologia,
23-25 January 2004, Granja, Portugal. Communication content published in (2004) Boletim da
SPHM 19(1):35.
Rosário, H.S. Intestinal ischemia-reperfusion and matrix metalloproteinase-9 – Trypsin is not

just for food. Invited seminar at the Instituto Gulbenkian de Ciência, Oeiras, Portugal, 23 April
2004.
Saldanha C., Chairperson in the Local Organizing Committee of the 23rd European Conference
on Microcirculation - “Microcirculation and Vascular Biology: A Basis for Research and a
Reason for Life” 8-11 September 2004, Lisboa, Portugal.
Saldanha, C., Member of the Organizing Committee of the 1st Workshop “Questões Éticas e
Sociais da Formação Médica”. 25 May 2004, Lisboa, Portugal.
Prizes
The Prize Dr. José Luís Champalimaud 2004 – Basic Research area (Comissão Nacional de Luta
contra a SIDA) was awarded (ex-æquo) to S. Veiga, S. Henriques, N.C. Santos and M. Castanho.
Santos, N.C. “Sistemas transportadores de fármacos e novas estratégias anti-HIV”. Colégio

Sagrado Coração de Maria, Lisbon, Portugal, 2 March 2004.
Saldanha, C. Member of the 1st Master Concil of Psicogerontology and Coordinator of the model
of “Basic Sciences and Aging Theories. FML/UL 2004-2006.

Clinical Immunology Unit
Branco Ferreira, M., M.C.Pereira Santos, M.L. Palma Carlos, M.A. Pereira Barbosa, A.G. Palma
Carlos (2004) Testes cutâneos versus imunoglobulinas específicas séricas para Dermatophagoides
pteronyssinus: avaliação comparativa da eficácia da imunoterapia específica. Revista Portuguesa
de Imunoalergologia 12: 239-50.
Branco Ferreira, M., M.C.Pereira Santos, A. Melo, M.L. Palma Carlos, M.A. Pereira Barbosa,
AG. Palma Carlos (2004) Moléculas de adesão na rinite alérgica e influência da imunoterapia
específica. Revista Portuguesa de Otorrinolaringologia e Cirurgia Cérvico-facial 42:123-31.
Maria, V.A. (2004) Promover a prática da Investigação Científica pelos alunos (editorial). Rev
FML 9:27-8.
Caldeira, L., Remísio, E., António, A., Aguiar, P., Fonseca, A., Vaz, F., Maria, V. (2004)
Prescrição de antibióticos para infecções do tracto respiratório em Portugal continental. Rev Port
Clin Geral 20:417-48.
Books/Book Chapters
Maria, V.A. Nota do Editor. In: Maria VA (ed) Farmacovigilância em Portugal. Lisboa,
INFARMED. 2003: 13-15.
Maria VA, Carmona R. Organização do Sistema Nacional de Farmacovigilância. In: Maria VA

(ed). Farmacovigilância em Portugal. Lisboa, INFARMED. 2003: 63-74.
Fonseca M, Maria VA. O notificador e a farmacovigilância: perspectiva do médico. In: Maria VA

(ed) Farmacovigilância em Portugal. Lisboa, INFARMED. 2003: 195-206.
Maria VA. Reacções adversas hepáticas. In: Maria VA (ed) Farmacovigilância em Portugal.
Lisboa, INFARMED. 2003: 273-290.
Maria VA. Farmacovigilância: perspectivas para o futuro. In: Maria VA (ed) Farmacovigilância
em Portugal. Lisboa, INFARMED. 2003: 473-480.
Barreto, M., Ricardo ferreira, Constantin Fesel, Maria Francisca Fontes, Eugénia Santos, M.
Alves, N. Cortez-Dias, Clara pereira, berta Martins, Rita Andreia, João Faro Viana, Francisco
Crespo, Carlos Vasconcelos, Luisa Mota-Vieira, Carlos Ferreira, Jocelyne Demengeot and Astrid
Moura Vicente. SLE patients have low frequency of regulated T cells which are highly heritable
and associated with CTLA4 and TGFb gene variants. Seventh International Congress: SLE and
Related Conditions, 9-13 May 1004, New York, USA.
Cavaleiro, R., A. Albuquerque, R.M.M. Victorino, A.E. Sousa. Immunosupressive Properties of

HIV2 Envelope Protein. British Society for Immunology – Annual Congress, Harrogate, UK, 7-
10 December 2004.
Cortesão, C., Russell B. Foxall, Adriana Albuquerque, Rui M.M. Victorino, Ana E. Sousa.
Similar Levels of Circulating Interleukin 7 in HIV1 and HIV2 Infections in Spite of Distinct Rates
of CD4 Depletion. 12th International Congress of Immunology and 4th Annual Meeting of
FOCIS, Montréal (Canada), 18-23 July 2004.
Costa, A.C., M.C. Pereira Santos, M.L. Palma Carlos, A.G. Palma Carlos. Solar urticária as
clinical manifestation of porphyria. XXII European Congress of Allergy and Clinical
Immunology 2004 (178): 60, June 2004, Amesterdam.
Foxall, R.B., C. Cortesão, A. Albuquerque, R.M.M. Victorino, A.E. Sousa. Characterization of

circulating CD4+CD25+ T cells in HIV 1 and HIV 2, two chronic human infections, with distinct
clinical outcomes. 12th International Congress of Immunology and 4th Annual Meeting of
FOCIS, Montréal (Canada), 18-23 July 2004.
Ferreira, R., Marta Barreto, Eugénia Santos, M. Alves, N. Cortez-Dias, Berta Martins, Rita
Andreia, Carlos Ferreira, Constantin Fesel. Evidence that genetic factors contribute to human
SLE by shaping natural IgM repetoires. Seventh International Congress: SLE and Related
Conditions, 9-13 May 2004, New York, USA.
Lopes Pregal, A., M.C. Pereira Santos, A. Spínola Santos, S. Lopes da Silva, M. Branco
Ferreira, E. Pedro, G. Palma Carlos, M.L. Palma Carlos, A.G. Palma Carlos, M.A Pereira
Barbosa. Allergic reactions to β-lactams – In vitro and in vivo diagnosis. XXII European
Congress of Allergy and Clinical Immunology 2004 (1064):312, June 2004,
Amesterdam.
Maria, V.A., Albuquerque, A., Sousa, A., Loureiro, A., Victorino, R.M. Severe and prolonged
cholestasis associated with pyritinol with evidence of srong specific T cell responses. Drug
Hypersensitivity Meeting, Bern, Switzerland, 5-8 May 2004.
Maria, V.A., Albuquerque, A., Victorino, R.M. Liver disease associated with allopurinol: clinical
and immunological studies in 7 cases. 20th International Conference on Pharmacoepidemiology
and Therapeutic Risk Management, Bordeaux, 22-25 August 2004.
Maria, V.A., Albuquerque, A., Victorino, R.M. Trimethoprim-sulphamethoxazole induced

hepatitis: evidence for an immunological mechanism. 20th International Conference on
Pharmacoepidemiology and Therapeutic Risk Management, Bordeaux, 22-25 August 2004.
Pimpão, C., I. Maestre, T. Moreno, J. Lacerda. Unrelated stem cell transplantation – anxiety
related to the unknown donor. EBMT 2004, Barcelona.
Rubio, S., Martins, C., Lacerda, J.F., Carmo, J.A., Lourenço, F., Lacerda, J.M.F. Allogeneic stem
cell transplantation (SCT) in patients with myelodisplastic syndromes (MDS) and secondary
acute leukemia (sAML): outcome analysis according to IPSS score. 7th Seminar - New Trends in
Acute Leukemia, Dubrovnik, Croatia, 11 September 2004.
Arcas, C., Juncal, C., Rodriguez, M.J., Martins, C., Nascimento, F., d’Avo, M., Lacerda, J.F.,
Galvão, M. Anemia hemolítica pós-transplante alogénico com condicionamento de intensidade
reduzida. Sociedade Portuguesa de Hematologia 2004, Carvoeiro
Cavaleiro, R., A. Albuquerque, R.M.M. Victorino, A.E. Sousa. Marked T cell suppressive effects
of HIV-2 envelope protein mediated by a monocyte-contact dependent mechanism. XXX Annual
Meeting Portuguese Society for Immunology, September 2004, Oeiras.
Costa, A.C., R Alves, S. Lopes da Silva, E. Pedro, M.C. Pereira Santos, M.A. Pereira Barbosa.
Efeitos secundários da dessensibilização ultra-rápida com veneno de himenópteros-estudo
retrospectivo. Revista Portuguesa de Imunoalergologia (C5):305. XXV Reunião Anual da
Sociedade Portuguesa de Alergologia e Imunologia Clínica, October 2004, Tomar.
Foxall, R.B., C. Cortesão, A. Albuquerque, R.M.M. Victorino, A.E. Sousa. The characterization
of circulating CD4CD25+ T cells in HIV1 and HIV2, two chronic human infections with distinct
clinical outcomes. XXX Annual Meeting Portuguese Society for Immunology, September 2004,
Oeiras.
Lopes Pregal, A., A. Spínola Santos, S. Lopes da Silva, E. Pedro, G. Palma Carlos, M.C. Pereira
Santos, M.A. Pereira Barbosa. Reacções alérgicas aos beta-lactâmicos-contribuição para o
diagnóstico. Revista Portuguesa de Imunoalergologia (P16):334. XXV Reunião Anual da
Sociedade Portuguesa de Alergologia e Imunologia Clínica, October 2004, Tomar.
Luís, E.B., Lacerda, J.F., Carmo, J.A., Lourenço, F., Martins, C., Lacerda, J.M.F. Doença
linfoproliferativa do sistema nervoso central associada ao vírus Epstein-Barr pós-transplante
alogénico de progenitores hematopoiéticos. Sociedade Portuguesa de Hematologia 2004,
Carvoeiro.
Lacerda, J.F. Novos estimuladores da Eritropoiese em Hematologia e Oncologia. Reunião Anual

da Sociedade Portuguesa de Hematologia 2004, 11 November 2004, Carvoeiro.
Maria, Vasco A.J. O ensino pré-graduado da Medicina Geral e Familiar em Portugal. I

Conferência Internacional sobre Formação em Medicina Geral e Familiar. Funchal, 23-24 April
2004.
Maria, Vasco A.J. Ética e Investigação em saúde: o doente enquanto objecto de estudo.
Workshop Questões éticas e sociais na formação médica. Faculdade de Medicina de Lisboa, 25
May 2004.
Maria, Vasco A.J. Formação pré-graduada em centros de saúde. Forum da Sociedade das
Ciências Médicas de Lisboa “Formação Médica em Centros de Saúde”. Lisboa, October 2004.
Maria, Vasco A.J. Competitividade da indústria farmacêutica e protecção da saúde pública.

Simposium Sistema Europeu de Avaliação e Supervisão de Medicamentos. Faculdade de
Medicina de Lisboa. 17 December 2004.
Victorino, Rui M.M. VIH/SIDA: sucessos, fracassos e futuro. Ciclo de Colóquios “Ao Encontro
da Medicina”. Fundação Calouste Gulbenkian – Sociedade das Ciências Médicas de Lisboa.
Lisboa, December 2004.
Maria, Vasco A.J. II Curso pós-graduado Introdução à Metodologia de Investigação. Faculdade

de Medicina de Lisboa (GAPIC). May-June 2004.
Maria, Vasco A.J. II Curso pós-graduado Introdução à Farmacoepidemiologia. Faculdade de

Medicina de Lisboa. 15 October - 17 December 2004.
Maria, Vasco A.J. 7º Workshop Educação pela Ciência. Gabinete de Apoio à Investigação
Científica, Tecnológica e Inovação (GAPIC). Faculdade de Medicina de Lisboa. Lisboa, 18
November 2004.
Maria, Vasco A.J. Simposium Sistema Europeu de Avaliação e Supervisão de Medicamentos.

Faculdade de Medicina de Lisboa. Lisboa, 17 December 2004.
Prizes
The Prize “Bolsa de Estudos VIH da Sociedade Portuguesa de Medicina Interna (SPMI)”was
awarded to Ana Espada de Sousa, Margarida Lucas, Rita Marçal, Adriana Albuquerque.
The Prize “Bolsa Bristol-Myers Squibb de Investigação da Associação Portuguesa para o Estudo
Clínico da SIDA (APECS)” was awarded to Ana Espada de Sousa, Margarida Lucas, Rita
Marçal, Adriana Albuquerque, and Rui MM Victorino.
The Prize “AMI – Saúde / “Doenças Infecciosas e Parasitárias – Menção Honrosa” was awarded
to Ana Espada de Sousa, Jorge Carneiro, M. Meier-Schellersheim, Zvi Grossman, and Rui MM
Victorino.
Cavaleiro, R.. “Vacinas”. Mestrado em Infecções Emergentes. FML, March 2004.
Foxall, R.. “Como avaliar respostas imunológicas específicas anti-microorganismos”. Mestrado

em Infecções Emergentes. FML, March2004.
Maria, V.A.J. Anti-hipertensores – critérios de escolha entre fármacos do mesmo grupo. IX

Jornadas de Cardiologia na Clínica Geral da Zona Sul. Lisboa, 20-21 May 2004.
Maria, V.A.J. Sistema Nacional de Farmacovigilância. Curso Cuidados Farmacêuticos na

Universidade, Farmácia Hospitalar e farmácia Comunitária. Instituto Superior de Ciências da
Saúde Sul. Monte da Caparica, 28-29 May 2004.
Maria, V.A.J. Prescrição racional no doente com osteoartrose e osteoporose. Curso Prescrição
Racional de Medicamentos. ARS do Alentejo. Beja, 12 October 2004.
Maria, V.A.J. Como escrever um projecto/protocolo de investigação: formulação de objectivos e

hipóteses. XI Jornadas de Pediatria. Lisboa, 20–23 October 2004.
Maria, V.A.J. Desenvolvimento e validação de indicadores de qualidade da prescrição. Curso

Melhoria da Qualidade em Saúde. Organização do IQS e Unidade D. Lisboa, 9 December 2004.
Sousa, A.E. e R.M.M. Victorino. “Aspectos imunológicos das imunodeficiências adquiridas”.

Mestrado em Imunologia Clínica da Universiade da Beira Interior, 2004.
Sousa, A.E.. “Imunopatogénese da Infecção VIH/SIDA”. Curso de Imunologia da Licenciatura

em Medicina do ICBAS. Porto, January 2004.
Sousa, A.E.. “Imunologia aplicada ao diagnóstico de infecções”. Mestrado de Microbiologia

Clínica. FML, February 2004.
Sousa, A.E.. “Imunobiologia da Infecção pelo VIH2”. Módulo de Virologia do Programa

GABBA. Faculdade de Farmácia da Universidade de Lisboa. March, 2004.
Sousa, A.E.. Responsável pelo Módulo de Imunologia do Mestrado em Infecções Emergentes.

FML, March 2004.
Sousa, A.E.. “Imunopatologia da Infecção pelo VIH”. Curso Pós-graduado Infecção VIH e
Tuberculose. FML, November 2004.
Victorino, R.M.M.. “O efeito da Imunologia Clínica e Avaliação do Sistema Imunitário”.

Mestrado em Doenças Infecciosas Emergentes, FML, March 2004.
Victorino, R.M.M. “Imunologia e Envelhecimento”. Mestrado em Psicogeontologia, FML, 2004
Victorino, R.M.M. “Ética da investigação em Medicina”. Mestrado em Bioética (Responsável

por um Módulo), FML, 2004.
Victorino, R.M.M. “Perspectivas sobre a infecção VIH/SIDA”. Mestrado em Sexologia, FML,

2004.

Gastroenterology Unit
Marinho, R. (2004) Hepatitis C prevention . GE – J. Port. Gastrenterol. 11:74-6
Books/Book Chapters
Carneiro de Moura, M. ( Editor ) (2004) Non Alcoholic SteatoHepatitis: From Cell Biology to
Clinical Pratice . EASL Monothematoc Conference. Estoril, Portugal, 17-18 September 2004.
Conference Syllabus. Centro de Gastrenterologia ( IMM ), pp 1-108.
Marinho, R., Velosa, J., Carneiro de Moura, M. (2004) Cento e vinte Perguntas sobre Hepatite C.
Quimera, Lisboa 2004. Portuguese adaptation of the book “Cent questions sur l´hépatite C”,
Patrick Marcellin, Thomas Laurtenceau, edition Frison-Roche 2003.
Portela-Gomes, G.M., Grimelius, L.,.Stridsberg, M., Falkmer, U., Falkmer, S. (2004)

Immunohistochemical studies with region-specific antibodies to chromogranins A, B and C in
pheochromocytomas. In: Cell Biology of the Chromaffin Cell. R. Borges, L. Gandia (Eds.).
Instituto Teófilo Hernando, Madrid, Spain, pp 147-149.
Carrilho-Ribeiro, L., Pinto-Correia, A., Velosa, J., Carneiro de Moura, M. Recurrence of

gallbladder stones after successful extra-corporeal lithotripsy is not universal: a 10 years
prospective study. 12nd United European Gastroenterology Week (UEGW) 2004, Prague, 25-
29 September 2004.
Cortez-Pinto, H., Martins, A., Machado, M., Gonçalves, M., Steffensen, S., Carvalho, T., Silva,
M.C., Marques-Vidal, P., Moura, M.C. Absence of association between promoter polymorphism
of tumor necrosis factor, valine-alanine manganese superoxide dismutase, interleukin 10 or cd14
endotoxin receptor gene and susceptibility to alcoholic liver disease”( Poster ) Postgraduate
course & 55th Annual Meeting of the American Association for the Study of Liver Diseases
(AASLD), Boston, USA, 1-4 November 2004.
Ramalho, R., Cortez-Pinto, H., Solá, S., Castro, R., Camilo, M.E., Moura, M.C., Rodrigues, C.
Enhanced apoptosis and bcl-2 protein production in the liver of patients with steatohepatitis. 39th
Meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany, April
14-18 2004
Serejo, F., Costa, A., Velosa, J., Carneiro de Moura, M. Progression of Fibrosis in Chronic
hepatitis C Treated with Interferon or Interferon and Ribavirin. Impact of Co-Factors: Alcohol,
Steatosis, Iron Serum Markers (Poster) Digestive Disease Week (DDW), American
Gastroenterology Association (AGA ), New Orleans, 15-20 May 2004
Serejo, F., Costa, A., Velosa, J., Carneiro de Moura, M. Liver Steatosis In Chronic Hepatitis C.
The Importance of Co-Factors: BMI, Alcohol, Lipids and Serum Markers of Iron Storage.
(Poster) Digestive Disease Week (DDW), American Gastroenterology Association (AGA ), New
Orleans, 15-20 May 2004
Siqueira, M., Rocha, P., Antunes, T., Carneiro de Moura, M. The role of nitric oxide, tumour
necrosis factor alpha and 3´5ćyclic guanosine monophosphate in Alcoholic Pancreatitis . 12th
UEGW, Prague, 25-30 September 2004.
Stridsberg, M., Portela-Gomes, G.M., Janson, E.T. Cellular localisation of chromogranins and
processed products in the diffuse neuroendocrine system and related tumours. 2nd Solstrand
Symposium - “In search of a functional role of Chromogranin A, Bergen, Norway, 23-24 January
2004
Tsokalis, A.V., Portela-Gomes, G.M., Stridsberg, M., Grimelius, L. et al . Malignant gastric

ghrelinoma with hyperghrelinemia. 15th International Symposium on Regulatory Peptides,
Toulouse, France, 19-22 September 2004
Carrilho Ribeiro, L., Pinto Correia, A., Velosa, J., Carneiro de Moura, M. A recidiva de litíase
vesicular após litotrícia extra-corporal por ondas de choque (LEOC) não é universal: um estudo
prospectivo a 10 anos. (Poster ) XXIV Congresso Nacional de Gastrenterologia, Figueira da Foz,
2-5 June 2004.
Marinho, R. Doença hepática alcoólica - carcinoma hepatocelular. 7ª Annual meeting of APEF,

Porto, 2-3 April 2004.
Marinho, R. Experiência clínica com adefovir dipivoxil Hepsera®. Health Challenge II, Évora,
May 2004.
Marinho, R. Score MELD: um substituto para a estratificação de Child-Pugh. Simpósio Clínico

“Destaques em Hepatologia”, XXIV Congresso Nacional de Gastrenterologia e Endoscopia
Digestiva, Figueira da Foz, 2-5 June 2004.
Marinho, R. , J. Giria, J. Catarino, M. Carneiro Moura. Aumento dos internamentos em portugal

por tumor maligno bilio-pancreático. XXIV Congresso Nacional de Gastrenterologia e
Endoscopia Digestiva, Figueira da Foz, 2-5 June 2004.
Marinho, R. Transaminases elevadas - diagnósticos difíceis. 17º Curso de Doencas

Hepatobiliares - Diagnóstico em hepatologia, Coimbra, October 2004.
Martins, A., Cortez-Pinto, H., Marinho, R., Fatela, N., Ramalho, F., Moura, M.C. Prevalência de
infecções fúngicas e bacterianas em doentes internados com cirrose hepática. XXIV Congresso
Nacional de Gastrenterologia, Figueira da Foz, 2-5 June 2004.
Martins, A., Cortez-Pinto, H., Marinho, R., Fatela, N., Ramalho, F., Moura, M.C. Hepatite aguda
alcoólica e pentoxifilina - experência de 2 anos numa Unidade de Hepatologia. XXIV Congresso
Martins, A., Cortez-Pinto, H., Marinho, R., Fatela, N., Ramalho, F., Moura, M.C. Pseudomixoma
peritonei. A propósito de um caso clínico. XXIV Congresso Nacional de Gastrenterologia,
Figueira da Foz, 2-5 June 2004.
Ramalho, R.M., Cortez-Pinto, H., Castro, R.E., Sola, S., Moura, M.C., Camilo M.E., Rodrigues,
C.M.P. Aumento da apoptose e Bcl-2 no fígado de doentes com esteatohepatite alcoólica (ASH) e
não-alcoólica (NASH). XXIV Congresso Nacional de Gastrenterologia, Figueira da Foz, 2-5 June
2004.
Serejo, F. Terapêutica da Hepatite crónica C. 7ª Annual meeting of the Associação Portuguesa

para o Estudo do Fígado ( APEF) , Porto, 2-3 April 2004
Sobral Dias, M., Cortez-Pinto, H., Fatela, N., Ramalho, F., Moura, M.C. Síndrome febril num
doente cirrótico. Caso clínico. XXIV Congresso Nacional de Gastrenterologia, Figueira da Foz,
2-5 June 2004.
Sobral Dias, M., Cortez-Pinto, H., Velosa, J., Moura, M.C. Doença de Wilson: forma de
apresentação e evolução clínica. Caso clínico. XXIV Congresso Nacional de Gastrenterologia,
Figueira da Foz, 2-5 June 2004.
Carneiro de Moura, M., Chairman . State of the Art Lecture on Treatment of chronic viral
hepatitis. VII Annual meeting of APEF , Porto , 1-2 April 2004
Carneiro de Moura, M. Postgraduate teaching in Hepatology in Europe. Meeting of the

Councillors of ASNEMGE with Presidents of European National Societies and the President of
the American Association of Gastroenterology ( AGA ), New Orleans , 16 May 2004.
Carneiro de Moura, M., Chairman . Alcohol and the Liver: From Molecular Biology to Clinics.
2004 Nordmann Award Meeting of the European Society for Biomedical Research on
Alcoholism , Lisbon, 27-28 May 2004.
Carneiro de Moura, M., Chairman. State of the Art lecture on Treatment of Hepatitis C.
Congresso Nacional de Gastrenterologia , Figueira da Foz , 2-5 June 2004.
Carneiro de Moura, M. Lecture: Non-Alcoholic Steatohepatitis. School of Gastroenterology

(Organized by OMGE e ASNEMGE ) Dubrovnik , 11-12 June 2004
Carneiro de Moura, M. Discussion of Clinical Cases (Liver). School of Gastroenterology

(Organized by OMGE e ASNEMGE ) Dubrovnik , 11-12 June 2004
Carneiro de Moura, M. Lecture: Drug induced liver disease. Gastroenterology OMGE

Gastroenterology Postgraduate Course, Rabat , 26 June-3 July 2004.
Carneiro de Moura, M. Clinical Cases ( Liver ): NASH and Hepatitis C. Gastroenterology OMGE
Gastroenterology Postgraduate Course, Rabat , 26 June-3 July 2004.
Carneiro de Moura, M., Coordinator. Introduction and Objectives. EASL Monothematic

Conference on NASH., Estoril , 17-18 September 2004.
Carneiro de Moura, M., Chairman. Session IV: Management of NAFLD. EASL Monothematic
Conference on NASH, Estoril , 17-18 September 2004.
Carneiro de Moura, M., Chairman. III Session: Patophysiology of Complications of Chronic Liver
Disease and Hepatic Carcinogenesis. International Conference: Frontiers in Hepatology,
Pamplona , 8-10 October 2004
Carneiro de Moura, M., Chairman and Moderator. State of the Art Lecture on Role of Liver
Biopsy. Jornadas de Hepatologia, Coimbra 15-16 October 2004.
Carneiro de Moura, M., Moderator. Session on Treatment of Chronic Hepatitis B. International

Simposium on Virology of Hepatitis B, Lisbon , 11 December 2004.
Carrilho Ribeiro, L. Colecistoses e lesões polipóides da vesícula biliar. XXIV Congresso

Cortez-Pinto, H. Chronic hepatitis C. The impact of steatosis and alcohol. Invited Lecture at the
II International Symposium on Viral Hepatitis of Lisbon, Lisbon, Portugal, 5-6 March 2004.
Cortez-Pinto, H. Moderator of oral communications: “Metabolic and drug-induced liver disease”.

39th Meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany,
14-18 April 2004.
Cortez-Pinto, H. Alcoholic liver disease and NASH: clinico-pathological correlates. Invited

lecture at the Session: “Alcohol and the liver: from molecular biology to clinics”. ESBRA
Nordman Award Meeting 2004 – Alcohol and Cannabis, organizado pela European Society of
Biochemical Research on Alcoholism (ESBRA), Lisbon, Portugal, 28-29 May 2004.
Cortez-Pinto, H. The role of liver biopsy in alcoholic and non-alcoholic fatty liver diseases”.
Invited lecture at the EASL Monothematic Single Topic Conference: “The role of liver biopsy in
the diagnosis and management of chronic liver disease”, EASL, Turin, Italy, 14-15 June 2004.
Cortez-Pinto, H. História natural da Esteatohepatite não alcoólica”. In the Session

“Esteatohepatite não alcoólica”. Invited Lecture at the II Reunião Ibérica de Hepatologia,
Marbella, Spain, 2-3 July 2004.
Cortez-Pinto, H. Pathophysiology and Natural History of Non Alcoholic Fatty Liver and Non
Alcoholic Steatohepatitis. Invited lecture at the 2004 Joint Annual Meeting of the Swiss Society
for Gastroenterology and Hepatology and the Swiss Society of Visceral Surgery, Montreux,
Switzerland, 9-11 September 2004.
Cortez-Pinto H,. Non-alcoholic fatty liver – iron metabolism. In the Session: “Nature or nurture
in liver disease: whose guilty is it?”. Invited lecture at the 26th European Society of Enteral and
Parenteral Nutrition (ESPEN), Lisbon, Portugal, 11-14 September 2004.
Cortez-Pinto, H. Oxidative stress in NAFLD”: here does it come from without the alcohol?
Invited lecture at the EASL Monothematic Conference: “Non-Alcoholic steatohepatitis: from cell
biology to clinical practice”, Estoril, Portugal, 17-18 September 2004.
Cortez-Pinto, H. NASH. Invited lecture in the State of the art liver lectures session of the United
European Gastroenterology Week (UEGW) 2004, Prague, Czech Republic, 26-29 September
2004.
Cortez-Pinto, H. Moderator of the “Lunch Session”: NASH/ASH. United European

Gastroenterology Week (UEGW) 2004, Prague, Czech Republic, 26-29 September 2004.
Cortez-Pinto, H. Encefalopatia. Invited lecture in the Session: “Complicações da cirrose”, during

the 17º Curso de Doenças Hepatobiliares, Coimbra, Portugal, 15-16 October 2004.
Cortez-Pinto, H. Moderator of the session: “Sindroma metabólica e interazione con HCV”. In the
meeting “Síndrome metabólica fegato e HCV”, organizado pela Universidade de Modena,
Modena, Italy, 19-20 November 2004.
Cortez-Pinto, H. Esteatohepatite. Invited conference at the Curso de Actualização em

Hepatologia – Reunião conjunta de Hepatologia do Hospital Central do Funchal e a APEF,
Funchal, 4 December 2004.
Marinho, R. Moderação do Simpósio “Prevenção e Tratamento das Hepatites Víricas”,

integrado no VI Congresso Médico Nacional dos Hospitais Distritais, Troia, April 2004.
Serejo, F. Invited lecture - Chronic hepatitis C : treatment of nonresponders. II Iberic Hepatology

Meeting , Marbella, Spain, 2-3 July 2004.
Serejo, F. Moderator of the Session Liver Nodule. Jornadas de Hepatologia, Coimbra 15-16
October 2004.
Carneiro de Moura, M., Coordinator (President) of the EASL Monothematic Conference on Non-
Alcoholic Steatohepatitis, Estoril, Portugal , 17-18 September 2004.
Carneiro de Moura, M., Chairman of the Symposium Alcohol and the Liver: From Molecular
Biology to Clinics, Nordmann Award Meeting 2004 of the European Society for Biomedical
Research on Alcoholism (ESBRA), Lisbon, 27-28 May 2004.
Carneiro de Moura, M. Conferência “Mudanças na Gestão da Saúde: O modelo canadiano”.

Hospital de Faro, Faro , Portugal 10 December 2004
Marinho, R. “Alcoolemia como factor de risco”. Fórum segurança rodoviária. Comissão de obras
públicas, transportes e comunicações, subcomissão de segurança rodoviária. Assembleia da
República, Lisboa, March 2004.
Marinho, R. “Doenças hepáticas víricas – mitos e realidades. impacto na saúde pública – da

epidemiologia à clínica”. XXI Jornadas Médico-Cirúrgicas de Gastrenterologia, Unidade de
Gastrenterologia do Serviço de Medicina 3 do Hospital Pulido Valente SA, March 2004.
Marinho, R. “Fígado artificial. Temas de Fronteira entre a Engenharia e a Medicina”

(Licenciatura de Engenharia Biomédica, Instituto Superior Técnico e Faculdade de Medicina de
Lisboa), Lisboa, April 2004.
Marinho, R. “Construção de quadros e gráficos”. Curso de Introdução à Metodologia de

Investigação, GAPIC, Instituto de Formação Avançada, Faculdade de Medicina de Lisboa, June
2004.
Marinho, R. “Como apresentar comunicação oral e poster”. Curso de Introdução à Metodologia

de Investigação, GAPIC, Instituto de Formação Avançada, Faculdade de Medicina de Lisboa,
June 2004.
Marinho, R. “Alcoolemia – factor de risco”. Fórum Segurança Rodoviária (Balanço Final do

Fórum), Assembleia da República, Sala do Senado, Lisboa, December 2004.
Marinho, R. “Alcoolemia e acidentes rodoviários”. R. Marinho. Seminários: “Gestão da Doença –

uma abordagem prospectiva em Saúde Pública”, Escola Nacional de Saúde Pública, December
2004.
Marinho, R. Moderação de sessão de comunicações no “7º Workshop Educação pela Ciência”,

GAPIC, Faculdade de Medicina de Lisboa, Lisboa, November 2004.
Thesis Completed
PhD Thesis
Fátima Serejo (2004) “Fibrogénese Hepática e Sobrecarga Oxidante na Hepatite C Crónica”.

Faculdade de Medicina da Universidade de Lisboa. Supervisor: M. Carneiro de Moura

Rheumatoid Arthritis Unit
Cruz, M., J.E. Fonseca, J.C. Branco (2004) Três anos de administração de etanercept e infliximab
a doentes com artrite reumatóide refractária - avaliação clínica e radiográfica e de segurança.
Acta Reumatológica Portuguesa 29:21-32.
Canhão, H., J.E. Fonseca, M. Viana Queiroz (2004) Questionário para identificação de factores de
risco de osteoporose. Acta Reumatológica Portuguesa 29:63-9.
Cruz, M., M. Mateus, J.E. Fonseca, J.C. Branco (2004) Agentes biológicos no tratamento de
doentes com artrite reumatóide refractária: melhor controlo da doença?. Acta Reumatológica
Portuguesa 29:89-95.
Canhão, H., J.E. Fonseca, M. Viana Queiroz (2004) Diagnóstico e terapêutica da osteoporose na
criança e no adolescente. Acta Médica Portuguesa 17:385-90.
Cavaleiro, J., J.E. Fonseca (2004) Gene do TNFalfa e Artrite Reumatóide: Prognóstico e
farmacogenética. Onde estamos e para onde vamos? Acta Reumatológica Portuguesa 29:233-242.
Fonseca, J.E. (2004) Artrite Reumatóide: contribuição do estudo da imunohistologia da mebrana

sinovial para o diagnóstico, terapêutica e avaliação do prognóstico da doença 2004; 9: 385-7.
Cavaleiro, J., Fonseca, J.E., Mourão, A.F., Sobral, M., Cruz, M., Carvalho, T., Canhão, H., Costa,
M.M., Castelão, W., Macieira, C., Santos, S.A., Laudim, E., Costa, R.P., Canas da Silva, J.,
Pereira da Silva, J.A., Viana Queiroz, M., Branco, J.C., Carmo Fonseca, M. (2004) Polymorphism
at position -238 of the tumor necrosis factor alpha and rheumatoid arthritis: prognosis and
pharmacogenetics- interim analysis (Poster). 5TH Annual EULAR Congress, Berlin, 9-12 June
2004
Fonseca, J.E., Carvalho, T., Cruz, M., Nero, P., Sobral, M., Mourão, A.F., Cavaleiro, J., Carmo
Fonseca, M., Branco, J.C. Polymorphism at position -308 of the promoter of the Tumor Necrosis
Factor α gene and infliximab therapy in rheumatoid arthritis (Poster). 2004 ACR Congress, San
Antonio, USA, 17-21 October 2004
XII Congresso Português de Reumatologia, Lisboa, 31 March - 3 April 2004:
1) Cruz, M., M. Mateus, J.E. Fonseca, J. Branco (2004) “Agentes Biológicos no

Tratamento de Doentes com Artrite Reumatóide Refractária: Melhor Controlo
da Doença?” (Poster).
2) Sobral, M., J.E. Fonseca, A.F. Mourão, M. Cruz, P. Nero, J. Cavaleiro, T.

Carvalho, H. Canhão, M.M. Costa, W. Castelão, C. Macieira, L. Miranda, S.A
Santos, E. Laudim, R.P. Costa, J. Vaz Patto, J. Canas da Silva, J.A Pereira da
Silva, M. Viana Queiroz, J.C. Branco, M. Carmo Fonseca (2004) “Polimorfismo
-308 do Gene do Factor de Necrose Tumoral Alfa e Artrite Reumatóide:
Potencial Relação com Actividade da Doença - Análise Preliminar” (Poster).
3) Araújo, P., R. Barros, F. Nogueira, D. Domingues, F. Exposto, J.B. Pimentão,
J.E. Fonseca, M. Mateus, A. Rosa, M.J. Martins, A. Matos, J. Branco (2004)
“Pesquisa de Micoplasmas Genitais na Artrite Reactiva (Resultados
Preliminares)” (Poster).
4) Barros, R., P. Araújo, A. Matos, M. Mateus, J.E. Fonseca, A. Rosa, J.B.
Pimentão, J. Branco (2004) “Síndrome Febril e Discite Séptica como
Manifestações de Endocardite Bacteriana a Enterococcus Faecalis” (Poster).
5) Barros, R., P. Araújo, A. Matos, M. Mateus, J.E. Fonseca, A. Rosa, J.B.
Pimentão, J. Branco (2004) “Tenosinovite Crónica Fistulizante dos Extensores
do Punho” (Poster).
6) Cobrado, N., Patrícia Nero, Jaime C. Branco e Grupo de Estudos CESAR. (2004)
“Avaliação da Qualidade de Vida (Qol) de Doentes com Artrite Reumatóide (AR)
Anterior à Introdução das Terapêuticas Biotecnológicas” (Communication).
7) Ligeiro, D., O. Abade, M. Cruz, I. Abreu, A.P. Almeida, P. Nero, J.E. Fonseca, R
.Sancho, H. Trindade, J. Machado Caetano, J. Branco (2004) “Polimorfismo
Genético na Artrite Reumatóide. Influência na Susceptibilidade e Actividade da
Doença” (Communication).
8) Fonseca, J.E., N. Cortez-Dias, A. Francisco, M. Sobral, H. Canhão, C Resende,
W. Castelão, C. Macieira, G. Sequeira, F. Saraiva, J.A. Pereira da Silva, M.
Carmo-Fonseca, M. Viana Queiroz (2004) “Infiltrado Inflamatório e Expressão
do RANKL/OPG na Artrite Reumatóide– Comparação com outras Artropatias
Inflamatórias e Correlação com a Evolução Clínica” (Communication).
9) Mourão, A.F., J.E. Fonseca, M. Sobral, M. Cruz, P. Nero, J. Cavaleiro, T.
Carvalho, H. Canhão, M.M. Costa, W. Castelão, C. Macieira, L. Miranda, S.A.
Santos, E. Laudim, R.P. Costa, J. Vaz Patto, J. Canas da Silva, J.A. Pereira da
Silva, M. Viana Queiroz, J.C. Branco, M. Carmo Fonseca (2004) “Polimorfismo
-238 do Gene do Factor de Necrose Tumoral Alfa e Artrite Reumatóide:
Potencial Relevância Prognóstica - Análise Preliminar” (Communication).
10) Nero, P., J.E. Fonseca, M. Cruz, M. Sobral, A.F. Mourão, J. Cavaleiro, T.
Carvalho, S.A. Santos, E. Laudim, R.P. Costa, J.C. Branco, M. Carmo Fonseca
(2004) “Polimorfismo -308 do Gene do Factor de Necrose Tumoral Alfa e
Terapêutica com Infliximab na Artrite Reumatóide: Potencial Relação Com
Resposta Clínica - Análise Preliminar” (Communication).
11) Cruz, M., J.E. Fonseca, J.C. Branco (2004) “Resultados de Três Anos de
Tratamento de Doentes com Artrite Reumatóide Refractária com Etanercept e
Infliximab na Unidade de Reumatologia do Hospital de Egas Moniz”
(Comunicação).
12) Araújo, P., R. Barros, S. Baptista, M.L. Vieira, M. Collares-Pereira, J.B.
Pimentão, J.E. Fonseca, M. Mateus, A. Rosa, M.J. Martins, A. Matos, J. Branco
(2004) “Pesquisa de Borrelia burgdorferi sensu lato e Anaplasma
phagocytophilum na Artrite Reactiva (Resultados Preliminares)” (Comunicação).
XXX Congresso Português de Imunologia, Oeiras, 30 September- 2 October 2004:

1) Cavaleiro, J., Fonseca, J.E., Teles, J., Sobral, M., Mourão, A.F., Cruz, M., Carvalho,
T., Canhão, H., Costa, M.M., Castelão, W., Macieira, C., Miranda, L., Santos, S.A.,
Laudim, E., Costa, R.P., Vaz Pato, J., Canas da Silva, J., Pereira da Silva, J.A., Viana
Queiroz, M., Branco, J.C., Carmo-Fonseca, M. Polymorphism at position -238 of the
Tumor Necrosis Factor α and Rheumatoid Arthritis: Prognosis and
pharmacogenetics.
2) Teles, J., Fonseca, J.E., Cavaleiro, J., Sobral, M., Mourão, A.F., Cruz M., Carvalho,
T., Canhão, H., Costa, M.M., Castelão, W., Macieira, C., Miranda, L., Santos, S.A.,
Laudim, E., Costa, R.P., Vaz Pato, J., Canas da Silva, J., Pereira da Silva, J.A., Viana
Queiroz, M., Branco, J.C., Carmo-Fonseca, M. Polymorphism at position -308 of the
Tumor Necrosis Factor α and Rheumatoid Arthritis: Prognosis and
pharmacogenetics.
Fonseca, J.E. (2004) “Artrite Reumatóide- Princípios terapêuticos fundamentais e consensus

para o início de terapêutica biológica”. Simpósio satélite “Novas perspectivas no controlo da
Artrite Reumatóide”, XII Congresso Português de Reumatologia, Lisboa, 31 March- 3 April
2004.
Fonseca, J.E. (2004) “Rheumatoid arthritis- a new era in prognosis and treatment”. XXX
Congresso Português de Imunologia, Oeiras, 30 September- 2 October 2004.
Fonseca, J.E. (2004) “Terapêutica biológica da AR nos centros de reumatologia portugueses”.

Jornadas de Outono e Reunião de abertura do ano académico da Sociedade Portuguesa de
Reumatologia, Lisboa, 8-20 October 2004.
Fonseca, J.E. (2004) “Espondiloartropatias Juvenis”. IX Jornadas Internacionais de

Reumatologia Pediátrica de Lisboa, Lisboa, 11-12 November 2004.
Fonseca, J.E. (2004) “Terapêutica das Artrites Idiopáticas Juvenis- presidência da mesa”. IX
Jornadas Internacionais de Reumatologia Pediátrica de Lisboa, Lisboa, 11-12 November 2004.
Fonseca, J.E. (2004) “Da clínica à investigação básica ”. XII Jornadas Internacionais do Instituto
Português de Reumatologia, Lisboa, 9-11 December 2004.
Fonseca, J.E. (2004) organização da mesa redonda intitulada “Novos Paradigmas terapêuticos na
artrite reumatóide”. XII Congresso Português de Reumatologia, Lisboa, 31 March - April 2004:
Curso de avaliação do doente com Espondilite Anquilosante, XII Congresso Português de

Reumatologia, Estoril, 31 March 2004:
Fonseca, J.E. (2004) “Terapêutica convencional”

Fonseca, J.E. (2004) “Caso clínico”
3º Curso prático de reumatologia da Faculdade de Medicina de Lisboa:
Fonseca, J.E. (2004) “Semiologia prática reumatológica”.

Fonseca, J.E. (2004) “Casos clínicos”.
21º Curso de reumatologia para pós-graduados, 6 and 7 May 2004.
Fonseca, J.E. (2004) “Antagonistas do TNF-α e da IL-1”.

Fonseca, J.E. e Fernando Neubarth (2004) “Mesa redonda de Osteoporose”.
Fonseca, J.E. (2004) “Tratamento da Espondilartrite Anquilosante e da Artrite Psoriática
com antagonistas do TNF-α”.
Fonseca, J.E. (2004) “Artrite Reumatóide. Para além dos antagonistas do TNF-α e da IL-
1”.
19º Curso de reumatologia para médicos de Medicina Geral e Familiar, 4 and 5 November 2004:
Fonseca, J.E. (2004) “Algumas particularidades da história clínica em reumatologia”.

Fonseca, J.E. (2004) “Exame objectivo reumatológico”.
Fonseca, J.E. (2004) “Apresentação, Discussão e Resolução de casos clínicos problema”.
Fonseca, J.E. (2004). Organization of the disciplines: Anatomia e Histologia (1º ano) and
Engenharia de Tecidos (4º ano) of Licenciatura em Engenharia Biomédica. Instituto Superior
Técnico/Faculdade de Medicina de Lisboa.
Fonseca, J.E. (2004). Organization of all the rheumatology lessons of Licenciatura em Medicina.

Molecular Microbiology and Infection Unit
Ramirez, M., Brito, D.A. and H. de Lencastre. Use of multiplex PCR for the detection of
pneumococcal multiple carriage. ISPPD-4, 4th International Symposium on Pneumococci and
Pneumococcal Diseases. Helsinki, Finland. May 9-13 2004.
Melo Cristino, J. “Resistências bacterianas em Portugal. Projecto Viriato”. 2º Encontro de

Pneumologia da Unidade D. Centro de Diagnóstico Pneumológico e Centro de Saúde da Venda
Nova. Lisboa, January 2004.
Melo Cristino, J. “Susceptibilidade aos antimicrobianos de bactérias responsáveis por infecções

respiratórias adquiridas na comunidade”. 1ª Reunião Pediátrica do Hospital Cuf Descobertas.
Lisboa, February 2004.
Melo Cristino, J. “Resistências aos Antibióticos”. Pandemias na Era da Globalização. Figueira da

Foz, April 2004.
Melo Cristino, J., T. Hänscheid and Ramirez, M:
Master Course in Clinical Microbiology 2003-04 and 2004-05, Faculty of Medicine of Lisbon.
Responsible for the organization and teaching of multiple courses.
Master Course in Emerging Infectious Diseases 2003-2004 and 2004-05, Faculty of Medicine of
Lisbon. Responsible for the organization of a module in Microbiology and teaching of multiple
courses.

Neurosciences Laboratory
Books/Book Chapters
Ribeiro, A. (2004) General aspects of neuropharmacology in relation to brain repair following

trauma. In: Brain Damage and Repair, T. Herdegen and J.M. Delgado-Garcia, pp 423-437.
Kluwer Academic Publishers, The Netherlands.
Ribeiro, J.A. (2004) Estimulantes do Sistema Nervoso Central. Antagonistas dos receptores da
adenosina: Alquilxantinas In: Terapêutica Medicamentosa e suas Bases Farmacológicas, ed., W.
Osswald and S. Guimarães, pp 139-146, Porto Editora, Porto.
Ribeiro, A. (2004) The Role of Adenosine as a Mediator of Cerebral Circulation. In: Circulation.
Ed. M. Valente-Alves and A Barbosa pp 130-137, Museu de Medicina, FML.
Sebastião, A.M. E Ribeiro, J.A. (2004) Sistema Purinérgico In: Terapêutica Medicamentosa e
suas Bases Farmacológicas, ed., W. Osswald and S. Guimarães, pp 440-451. Porto Editora, Porto.
Cascalheira, J.F., Sebastião, A.M., Ribeiro, J.A . A1 adenosine receptor activation inhibits both
basal and histamine-stimulated inositol phosphastes acumulation in the rat hippocampus. FENS
Forum 2004, 10-14 July 2004, Lisboa.
Coelho, J.E. Pinto-Duarte, A., Ribeiro, J.A. and Sebastião, A.M. A2A receptor activation
enhances adenosine transport through a PKC dependent mechanism. EPHAR 2004, 14-17July
2004, Porto
Costa, V., Cardoso, N., Kupsch, K., Pinto-Duarte, A., Sebastião, A.M., Ribeiro, J.A. BDNF
facilitation of [3H] acetylcholine release from rat hippocampal slices is dependent on adenosine
A2A receptor activation. FENS Forum 2004, 10-14 July 2004, Lisboa.
Cunha-Reis, D., Illes, P., Wirkner, K., Ribeiro, J.A., Sebastião, A.M. VIP facilitates GABAergic
currents recorded either from interneurones or pyramidal cells in the CA1 area of the rat
hippocampus. FENS Forum 2004, 10-14 July 2004, Lisboa.
Cunha-Reis, D., J.A. Ribeiro, A.M. Sebastião. VIP modulates K+-evoked [3H]-GABA Release
from hippocampal synaptosomes through activation of both VPAC1 and VPAC2 receptors.
EPHAR 2004, 14-17 July 2004, Porto.
Diógenes, M.J., Fernandes, C., Sebastião, A.M., Ribeiro, J.A. Cross-talk between adenosine
receptors and brain-derived neurotrophic factor (BDNF) receptors. Purines 2004, 6-9 June
2004, Chappel Hill, USA.
Diógenes, M.J., Ribeiro, J.A., Sebastião, A.M. Adenosine enhances the BDNF excitatory action
on synaptic transmission at the rat hippocampus through cyclic AMP/PKA signalling system.
FENS Forum 2004, 10-14 July 2004, Lisboa.
Diógenes, M.J., Ribeiro, J.A. and Sebastião, A.M. BDNF Actions on Synaptic Transmission at the
Hippocampus. Brain Damage & Repair, July 2004, Lisboa
Diógenes, M.J., J.A. Ribeiro, A.M. Sebastião. Endogenous A2A receptor activation trigger the
BDNF excitatory action on synaptic transmission. EPHAR 2004, 14-17 July 2004, Porto.
Fernandes, C.C., Maria J. Diógenes M.J, Ribeiro, J.A. and Sebastião, A.M. Presynaptic
mechanisms facilitate excitatory action of brain derived neurotrophic factor on hippocampal
synaptic transmission. Purines 2004, 6-9 June 2004, Chappel Hill, USA.
Fernandes, C.C., Ribeiro, J.A., Sebastião, A.M. Presynaptic depolarisation facilitates excitatory
action of brain derived neurotrophic factor on hippocampal synaptic transmission. FENS Forum
2004, 10-14 July 2004, Lisboa.
Fernandes, C., Ribeiro J.A. and Sebastião, A.M. The excitatory action of BDNF on hippocampal
synaptic transmission does not depend on postsynaptic depolarisation or postsynaptic
enhancement of camp. EPHAR 2004, 14-17 July 2004, Porto.
Fernandes, C., Ribeiro, J.A. and Sebastião, A.M. Excitatory action of brain-derived neurotrophic
factor on hippocampal synaptic transmission depends on presynaptic depolarisation. Brain
Damage & Repair, July 2004, Lisboa
Fragata, I.R., Sebastião, A.M., and Ribeiro, J.A. Nitric oxide mediates interactions between
GABA-A receptors and adenosine A1 receptors at the rat hippocampus. FENS Forum 2004, 10-
14 July 2004, Lisboa
Fragata, I.R., Sebastião, A.M., and Ribeiro, J.A. GABA-A receptor blockade facilitates the
inhibitory action of adenosine on synaptic transmission. EPHAR 2004, 14-17 July 2004, Porto
Pereira, I.T., Sebastião, A.M. and Ribeiro, J.A The effect of brain-derived neurotrophic factor
(BDNF) on 3H-gamma-aminobutyric acid (3H-GABA) release from rat hippocampal
synaptosomes involves GABA transporters. FENS Forum 2004, 10-14 July 2004, Lisboa
Pereira, I.T., Canas, N., Sebastião, A.M. and Ribeiro, J.A. Different mechanisms are involved in
the modulatory action of BDNF on transmitter releasew in the rat hippocampal synaptosomes.
EPHAR 2004, 14-17 July 2004, Porto
Pereira, I.T., Canas, N., Sebastião, AM. And Ribeiro, J.A. BDNF modulates glutamate and GABA
release from hippocampal synaptosomes through different mechanisms. Brain Damage Repair,
July 2004, Lisboa
Pinto-Duarte, A., J.E. Coelho, R.A Cunha, A.M. Sebastião, Ribeiro, J.A. Differential activation
of adenosine receptors influences nucleoside transporters activity in the rat hippocampus.
Purines 2004, 6-9 June 2004, Chappel Hill, USA.
Pinto-Duarte, A., Coelho, J.E., Cunha, R.A., Sebastião, A.M., Ribeiro, J.A. Cross-talk between
adenosine A2A receptors and nucleoside transpoters in the rat hippocampus. FENS Forum 2004,
10-14 July 2004, Lisboa.
Pinto-Duarte, A., Carrapiço, E., Ferreira, A.R., Cardoso, N., Costa, V., Sebastião, A.M, and
Ribeiro, J.A. BDNF facilitates electrically evoked 3H-acetylcholine release from rat hippocampal
slices. EPHAR 2004, 14-17 July 2004, Porto.
Santos, A., Pinto-Duarte, A., Coelho, J.E., Sebastião, A.M., Ribeiro, J.A. Relative contribution of
voltage-dependente calcium channels for electrically-evoked [3H] acetylcholine release from
hippocampal slices. FENS Forum 2004, 10-14 July 2004, Lisboa.
Santos, A.S., Pinto-Duarte, A., Coelho, J.E., Sebastião, A.M., and Ribeiro, J.A. Role of voltage-
dependente calcium channels in the release of [3 H] acetylcholine from rat hippocampus slices
under low-frequency electric stimulation. EPHAR 2004, 14-17 July 2004, Porto
Sebastião, A.M., Ribeiro, J.A. Adenosine released during hypoxia triggers a post-hypoxia
excitatory action of BDNF on hippocampal synaptic transmission. Purines 2004, 6-9 June 2004.
Chappel Hill, USA.
Diógenes, M.J. BDNF Actions on Synaptic Transmission at the Hippocampus. FENS 2004
Satellite Symposium on ‘Brain damage and Repair’. Lisboa, July 2004.
Ribeiro, J.A. Invited to deliver the plenary lecture ‘How Adenosine Receptors Fine Tune
Neurotransmission to Protect the Brain’, Purines Meeting, 23 September 2004, Rome.
Ribeiro, J.A. Iinvited to deliver the lecture ‘How Purines Protect the Brain’. Brain Damage and
Repair Meeting, 7 July 2004, Lisboa.
Ribeiro, J.A. Iinvited to deliver the lecture, ‘Adenosine modulation of sodium uptake’. Brain
Regeneration Meeting, 23-24 April 2004, Zagreb.
Ribeiro, J.A. Invited to deliver the lecture ‘Adenosine Receptors:Pathophysiological

Implications’. In P1 Purinoceptors: Therapeutic Implications for CNS disorders”. EPHAR
Meeting, 14-17 July 2004, Porto.
Sebastião, A.M. Neuromodulation by Adenosine: Key Role of A2a Receptors. European Winter
Conference on Brain Research, Les Arcs, March 2004.
Sebastião, A.M. Regulation of Synaptic Actions of Neurotrophins by Adenosine. Federation of

European Neurosciences Forum, Lisboa, July 2004.
Sebastião, A.M. Adenosine Receptors. Seminar at the Institute for Pharmacology and Toxicology,
University of Zurich. Invitation by Dr. Detlev Boison.
Ribeiro, J.A. Member of the Scientific Committee and of the Organizing Committee of the
Federation of European Neuroscience Societies (FENS) meeting, Lisboa, 10-14 July 2004.
Ribeiro, J.A. Member of the Scientific Committee of the ‘International Congress: Purines
2004’, Chapel Hill, North Carolina, USA, 6-9 June 2004.
Ribeiro, J.A. Organizer of the Symposium ‘Purinoceptors-I’ of the European Pharmacological

Congress (EPHAR) meeting, Porto, 14-18 July 2004.
Ribeiro, J.A. Organizer and President of the Scientific Committee of the International Meeting on
‘Brain Repair and Neuroprotection’, Lisboa, 8-9 July 2004.
Sebastião, A.M. Member of the Organizing Committee of Federation of European Neuroscience

Societies (FENS) meeting, Lisboa 10-14 July 2004.
Sebastião, A.M. Member of the Organizing and Scientific Committees of European

Pharmacological Societies (EPHAR) meeting, Porto 14-18 July 2004
Ribeiro, J.A. Coordinator and lecturer of the Master’s course in Neurosciences, FML.
Ribeiro, J.A. Lecture on Neuroethics in the Master’s course in Bioethics, February 2004, FML.
Ribeiro, J.A. Lecture on Neurochemical Pharmacology in the Master’s course in Human

Sexuality, October 2004, FML.
Ribeiro, J.A. Chairman of a Panel on Pharmacogenetics, 29 April 2004, FML.
Ribeiro, J.A. Organizer of the Brain Awareness Week (DANA-EDAB initiatives), 15-22 March
2004 with interviews on TV, radio and daily newspapers. Participation in lectures at Secondary
Schools.
Sebastião, A.M. “Técnicas Electrofisiológicas”, Faculdade de Farmácia, Universidade de Lisboa,

March 2004, invited by Professor Rui Silva.
Sebastião, A.M. “Drogas e Cérebro” – Debate na Escola Secundária de Cascais, inserido na

Semana Internacional do Cérebro, March 2004.
Sebastião, A.M. “Brain awareness Week in 2004, Portugal” – Report of activities at a Round
table promoted by the DANA Foundation at the FENS 2004 Forum, Lisboa, July 2004.
Sebastião, A.M. Supervision of the project ‘Agressão aguda (hipóxia) a células nervosas: acção
das neurotrofinas e da adenosina’ promoted by GAPIC, Faculty of Medicine, as an incentive for
scientific investigation to Medical students: Student: Gabriel Oliveira. Results reported to the 7th
Workshop on Educação para a Ciência, Faculdade de Medicina, Lisboa, November 2004.
Sebastião, A.M. and A. Pinto-Duarte co-supervision of the project ‘Modulação do Transportador

de Colina por Neurotrofinas e por Adenosina’ promoted by GAPIC, Faculty of Medicine, as an
incentive for scientific investigation to Medical Students: Students: Eunice Carrapiço, Ana Rita
Ferreira. Results reported to the 7th Workshop on Educação para a Ciência, Faculdade de
Medicina, Lisboa, November 2004.
Sebastião, A.M., and A. Pinto-Duarte co-supervision of the project ‘:Modulação da Libertação de

Acetilcolina pelas Neurotrofinas: Interacção com a Adenosina promoted by GAPIC, Faculty of
Medicine, as an incentive for scientific investigation to Medical Students: Students: Nicole
Cardoso, Vânia Costa. Results reported to the 7th Workshop on Educação para a Ciência,
Faculdade de Medicina, Lisboa, November 2004.
Thesis Completed
Master Thesis
Isabel Fragata (2004) ‘Interaction between GABA and adenosine in hippocampal slices’.
Master’s degree thesis in Neurosciences, Faculdade de Medicina da Universidade de Lisboa.
Supervisors: J Alexandre Ribeiro and Ana M. Sebastião.
Nuno Félix (2004) ‘Interactions between adenosine receptors and ATP receptors on control of
ventilation’. Master’s Degree Thesis in Neurosciences, Faculdade de Medicina da Universidade
de Lisboa. Supervisors: J Alexandre Ribeiro and L. Silva-Carvalho.
Diploma Thesis (Teses de Licenciatura)
Inês Pereira (2004) ‘BDNF inhibits 3H-GABA release from rat hippocampal synaptosomes’.
Undergraduate Degree Thesis in Biology, Faculdade de Ciências da Universidade de Lisboa.
Supervisor: J Alexandre Ribeiro.

Neurosciences Laboratory & Dementia Research Group
de Mendonça, A. (2004) Defeito Cognitivo Ligeiro. Mundo Médico 33:32-33.
de Mendonça, A., Guerreiro, M. (2004) Algumas Considerações Ligeiras Acerca do Defeito

Cognitivo. Em memória do Professor Carlos Garcia. Revista da Faculdade de Medicina de Lisboa
9:451-453
de Mendonça, A. Changes in memory and the impression about memory during lifetime.
Symposium “The Ageing Brain”, FENS Forum 2004, Lisboa.
de Mendonça, A. Fisiopatologia da Doença de Alzheimer. I Simpósio da Memória, Porto, 14

February 2004.
de Mendonça, A. Defeito Cognitivo Ligeiro. 11as Jornadas de Saúde Mental do Algarve, simpósio
Do Defeito Cognitivo Ligeiro à Demência de Alzheimer, Carvoeiro, 23 April 2004.
de Mendonça, A. Defeito Cognitivo Ligeiro. Reunião do Serviço de Psiquiatria do Hospital de S.

Bernardo, Setúbal, 29 April 2004.
de Mendonça, A. Co-morbilidade na doença de Alzheimer. Forum Neurologia 2004, Luso, 22

May 2004.
de Mendonça, A. Clínica de Memória. Encontro de Psicogeriatria, mesa redonda Novas

Abordagens em Psicogeriatria, Porto, 30 September and 1 October 2004.
de Mendonça, A. Diagnóstico precoce. I Encontro Bial de Neurologia, Angra do Heroísmo, 13

November 2004.
de Mendonça, A. Caffeine and Memory. Conferência Bissaya Barreto, Coimbra, 28 May 2004.
de Mendonça, A. Co-chaired the Symposium The Ageing Brain, Federation of European

Neurosciences Society, Lisbon, 2004.
de Mendonça, A. Co-chaired the Symposium Neurodegenerative Disorders, XIV Congresso

Nacional de Bioquímica, Vilamoura, 2004.
de Mendonça, A. Chaired the Symposium Memantina e Neuroprotecção, Estoril, 2004.
Undergraduate teaching
Participation in the teaching of Neurosciences and Neurology at the FML.
Collaboration in the teaching at Instituto de Ciências Biomédicas Abel Salazar da Universidade

do Porto, and Faculdade de Farmácia de Lisboa.
Post-graduate teaching
Participation in the teaching of the Master Degree in Neurosciences at the FML.
Collaboration in several advanced courses in the area of Dementia in Escola Superior de Saúde de
Alcoitão and Escola Superior de Enfermagem Calouste Gulbenkian.
Collaboration in the training of general practioners, pharmacists and formal caregivers.
Thesis Completed
Master Thesis
Tiago Mendes (2004) “Memory and Metamemory: from the Young to The Aged”. Master Degree
Thesis in Neurosciences, Faculdade de Medicina da Universidade de Lisboa. Supervisors:
Alexandre de Mendonça and Manuela Guerreiro.

Electromyography and Evoked Potentials Laboratory
Atalaia, A., de Carvalho, M., Pinto, A., Evangelista, T. Sleep Characteristics of Amyotrophic
Lateral Sclerosis Patients with Preserved Diaphragmatic Function. 2nd European ALS
Consortium Research Workshop, Nice, May 2004.
de Carvalho, M., Scotto, M., Lopes, A., Swash, M. Neurophysiological Measurement of

Progression in ALS - a Prospective Study. Association of British Neurology Spring Scientific
Meeting London, April 2004.
de Carvalho, M., Costa, J., Swash, M. Clinical Trials in ALS and the Role of the
Neurophysiology. 2nd European ALS Consortium Research Workshop, Nice, May 2004.
de Carvalho, M., Scotto, M., Lopes, A., Swash, M. Rate of Decay of the Number of Motor Units
and Neurophysiological Index in Amyotrophic Lateral Sclerosis. VIII Quantitative EMG
Congress, Nimjegen, June 2004.
de Carvalho, M., Swash, M. Progressive Muscle Atrophy Presenting with “Benign” Cramps,
Muscle Pain and Fasciculations.. 8th Congress of the European Federation of Neurological
Societies, Paris, September 2004.
de Carvalho, M., Costa, J., Swash M. Clinical Trials in ALS and the Role of the
Neurophysiology. 14th International Symposium ALS/MND. Philadelphia, December 2004.
Pugdhal, K., Tankisi, H., Fuglsang-Fredericksen, A., Johnsen, B., de Carvalho, M., Fawcett,
P.R.W., Labarre-Vila, A., Liguori, R., Nix, W., Schofield, I.S. European Variation in the
Electrophysiological Examination of Anterior Horn Cell Disorders. VIII Quantitative EMG
Rocha, M.L., Evangelista, T., de Carvalho, M. The Impact of Dysphagia on the Quality of LIfe in
ALS Patients. 2nd European ALS Consortium Research Workshop, Nice, May 2004.
Tankisi, H., Pugdhal, K., Fuglsang-Fredericksen, A., Johnsen, B., de Carvalho, M., Fawcett,
P.R.W., Labarre-Vila, A., Liguori, R., Nix, W., Schofield, IS. The Influence of the Medical Audit
on the Pathophysiological Interpretation of Nerve Conduction Studies. VIII Quantitative EMG
Almeida, R., de Carvalho, M., Evangelista, T., Costa, J. Study of Golgi Proteins in Amyotrophic
Lateral Sclerosis. XIV Congresso Nacional de Bioquímica. Vilamoura, December 2004.
Costa, J., Evangelista, T., de Carvalho, M. Parésia Unilateral do Diafragma na Miopatia das
Cinturas. Reunião da Sociedade Portuguesa de Doenças Neuromusculares, Tomar, May 2004.
Costa, J., de Carvalho, M. Utilização Terapêutica das Imunoglobulinas em Doenças

Neuromusculares – Revisão Sistematizada da Literatura. Forum de Neurologia 2004, Luso, May
2004.
Costa, J., de Carvalho, M. Lesão Severa do Nervo Frénico na Polineuropatia Inflamatória

Desmielinizante Crónica, com Resposta à Terapêutica. Forum de Neurologia 2004, Luso, May
2004.
de Carvalho, M., Guedes, L., Ferreira, J. Doente com Vómitos, Cefaleias, Parésia dos
Movimentos Oculares e Faciais, em Associação com Midríase. Reunião de Inverno da Sociedade
Portuguesa de Estudos de Doenças Neuromusculares, Lisboa, November 2004.
Evangelista, T., Barroso, C., de Carvalho, M. Falta de Força Localizada no Antebraço. Reunião
de Inverno da Sociedade Portuguesa de Estudos de Doenças Neuromusculares, Lisboa, November
2004.
Evangelista, T., de Carvalho, M., Andersen, P. ELA-DNM – Mutação do Gene da SOD1. Reunião
de Inverno da Sociedade Portuguesa de Estudos de Doenças Neuromusculares, Lisboa, November
2004.
Geraldes, R., Santos-Bento, M., Nicholson, G., de Carvalho, M. Neuropatia Sensitiva Hereditária
tipo I (HSN 1) numa Família Portuguesa – Avaliação Electrodiagnóstica e Estudo do Sistema
Nervoso Autonómo. Forum de Neurologia 2004, Luso, May 2004.
Geraldes, R., Jorge, Z., Conceição, I., Carmo, I., Nunes; P.A., Brito, M.J., Lemos, M., Galvão-
Teles, A., de Carvalho, M. Precocidade das Alterações Neurofisiológicas na
Adrenoleucosdistrofia (ALD). Congresso de Neurologia 2004, Granja, November 2004.
Geraldes, R; de Carvalho, M. Xantomatose Cerebrotendinosa (XCT): aspectos clínicos, genéticos

e electrofisiológicos. Congresso de Neurologia 2004, Granja, November 2004.
Geraldes, R., Proença, S., Evangelista, T., de Carvalho, M. Pressão Máxima de Inalação Nasal
(SNIP) - Observações em Controlos e em Doentes com Esclerose Lateral Amiotrófica (ELA).
Congresso de Neurologia 2004, Granja, November 2004.
Graça, P., Evangelista, T., de Carvalho, M. Doente com Dor e Hipertrofia dos Músculos
Posteriores da Perna Direita. Reunião da Sociedade Portuguesa de Doenças Neuromusculares,
Tomar, May 2004.
Macieira, C., Susana, P., de Carvalho, M. Doente com Neuropatia e Sinais Piramidais. Reunião
da Sociedade Portuguesa de Doenças Neuromusculares, Tomar, May 2004.
Peralta, AR., de Carvalho, M., Evangelista, T., Sá. J. Alteração da Excitabilidade Neuromuscular
na Hipocaliémia Iatrogénica. Forum de Neurologia 2004, Luso, May 2004.
Susana, P., Macieira, C., de Carvalho, M. Doente com Parésia da Mão. Reunião da Sociedade
Portuguesa de Doenças Neuromusculares, Tomar, May 2004.
Susana, P., Macieira, C., de Carvalho, M. Doença de McArdle – revisão de 11 casos. Reunião da
Sociedade Portuguesa de Doenças Neuromusculares, Tomar, May 2004.
de Carvalho, M. Como pode a Neurofisiologia Medir a Progressão da Perda Neuronal na

Esclerose Lateral Amiotrófica. Reunião Anual da Associação Portuguesa de EEG e
Neurofisiologia Clínica. Porto, April 2004.
de Carvalho, M. Conferência de Homenagem à Profª Doutora Sales Luís, promovida pela

Sociedade Portuguesa de Neurologia. Forum de Neurologia 2004, Luso, May 2004.
de Carvalho, M. What is the Contribution of the Clinical Neurophysiology to Measure Disease

Progression in ALS. 2nd European ALS Consortium Research Workshop, Nice, May 2004.
de Carvalho, M. Co-organized the Workshop on Neurophysiology. 2nd European Consortium of

ALS, Nice, May 2004.
de Carvalho, M. Co-organized the Symposium on Neurologist in the Emergency Room. Fórum da

Sociedade Portuguesa de Neurologia, Luso, May 2004.
de Carvalho, M. Co-chaired the Session on Surrogate Markers in the 15th International

Symposium on ALS/MND, Philadelphia, December 2004.
Prizes
The 1st Prize (ex-equo) for best poster in “2º Congresso Português de Doenças Neuromusculares,
2004” was awarded to Costa, J., Evangelista, T., Conceição, I. and de Carvalho, M.
The 2nd Prize “Corino de Andrade-Novartis” from “Sociedade Portuguesa de Neurologia” 2004
was awarded to Costa, J., Evangelista, T., Conceição, I. and de Carvalho, M.

Neuropathology Laboratory
Pimentel, J. (2004) Patologia dos tumours cerebrais. RFML 9:445-449.
Pimentel, J. CJD Surveillance in Portugal. NEUROCJD Meeting, Roskilde, Denmark, June

2004.
Pinto, F., Evangelista, T., Santos, R. Neurogenic muscle weakness, ataxia, retinitis pigmentosa
and epilepsy (NARP). Internacional Congress of Epilepsy, Lisboa, 2004.
Barroso, C., Galán, L., Gouveia, C., Vieira, E., Oliveira, J., Santos, R., Melo Pires, M.,
Guimarães, A. Disferlinopatias: estudo clínico, histopatológico e genético de 9 casos. Forum de
Neurologia. Luso, May 2004.
Barroso, C., Costa, J., Sá, J., Cristino, N., Mascarenhas, F., Pimentel, J. Gliomatose cerebri: um
tumor cerebral raro. Forum de Neurologia. Granja, November 2004.
Bugalho, P., Mascarenhas, F., Firmo, C, Pimentel, J. Meduloblastoma em doentes com mais de 40
anos. Forum de Neurologia. Granja, November 2004.
Calado, S., Miguéns, J., Pimentel, J. Quisto congénito dos plexos coroideus – caracterização
clínica e neuropatológica. Forum de Neurologia. Luso, May 2004.
Correia-Guedes, L., Ferreira, J., Coelho, M., Campos, A., Almeida, A., Biscoito, L., Almeida, M.,
Pimentel, J. Plexopatia braquial bilateral como apresentação clínica de linfoma de células B.
Forum de Neurologia. Luso, May 2004.
Costa, J., Ruivo, J., Cristino, N., Sá G., Miguéns, J., Lobo Antunes, J., Pimentel, J.
Ganglioglioma do cone medular. Forum de Neurologia. Luso, May 2004.
Costa, J., Barroso, C., Coiteiro, D., Miguéns, J., Lobo-Antunes, J., Pimentel J. Localizações raras
de metástases no neuro-eixo. Forum de Neurologia. Granja, November 2004.
Nunes de Oliveira, S., Melancia, J., Cortes, P., Pimentel, J. Compressão medular como
manifestação inaugural de tumor do seio endodérmico. Forum de Neurologia. Granja, November
2004.
Nunes de Oliveira, S., Lobo Antunes, J., Pimentel, J. Pseudotumor inflamatório do sistema
nervos central. Forum de Neurologia. Granja, November 2004.
Pinto, F., Pimentel, J. Partners in epilepsy (PIE): uma ferramenta electrónica internacional de
gestão de informação na epilepsia. Resultados preliminares da consulta de epilepsia no Hospital
de Santa Maria. Forum de Neurologia. Granja, November 2004.
Pinto, M., Guimarães, A., Barroso, C., Santos, R., Santos, M. Miofasceíte macrofágica e distrofia
de Becker: caso clínico infantil. Forum de Neurologia. Luso, May 2004.
Roque, R., Cristino, N., Miguéns, J., Pimentel, J. Tumor neuroepitelial disembrioplástico (DNET)
com localização rara. Forum de Neurologia. Granja, November 2004.
Sousa, R., de Sá, J., Albuquerque, L., Pimentel, J. Leucoencefalopatias desmielinizantes agudas
pseudo-tumorais. Forum de Neurologia. Luso, May 2004.
Pimentel, J. Epilepsia e co-morbilidades. 16th National Meeting on Epilepsy. Lisboa, March

2004.
Pimentel, J. Idade e epilepsia. 16th National Meeting on Epilepsy. Lisboa, March 2004.
Pimentel, J. 4th Course of Epilepsy. FML, January 2004.
Barroso, C. Patologia não neoplásica do nervo periférico. Curso PROFIN de Neuropatologia –

Forum de Neurologia. Luso, May 2004.
Evangelista, T. Patologia muscular não neoplásica. Curso PROFIN de Neuropatologia – Forum

de Neurologia. Luso, May 2004.
Evangelista, T. Patologia do músculo. Curso de Pós-Graduação em Medicina Desportiva. Lisboa,

2004.
Pimentel, J. General aspect of epilepsy. 4th Curso de Epilepsia. FML, January 2004.
Pimentel, J. Pharmacological treatment of epilepsies. 4th Curso de Epilepsia. FML, January 2004.
Pimentel, J. Aspectos embriológicos e patológicos. 5º Mestrado em Neurociências. FML, March

2004.
Pimentel, J. Patologia neoplásica do SNC. Curso PROFIN de Neuropatologia – Forum de

Neurologia. Luso, May 2004.
Pimentel, J. Caso neuropatológico. 5º Mestrado em Neurociências. FML, May 2004.

Pimentel, J. Doenças priónicas. Pós-Graduação em Segurança Alimentar e Microbiologia

Aplicada. Universidade Católica do Porto, July, 2004.
Pimentel, J. Doenças causadas por priões. II Curso de Mestrado em Doenças Infecciosas

Emergentes. FML, November 2004.
Pimentel, J. Sexualidade e epilepsia. Mestrado em Sexualidade Humana. FML, November, 2004.

Functional Neuroanatomy Laboratory
Gonçalves Ferreira, A.J., P. Pereira, L.L. Neto, S.M. Barata, T. Fonseca, P. Soares, J. Rino.
Anatomy/MRI Comparative Study of the Normal Hippocampal Volume. 16th Congress of the
European Society for Stereotactic and Functional Neurosurgery (ESSFN), Vienna, June 2004.
Gonçalves Ferreira, A.J., P.S. Fernandes, H. Cardoso, B. Miranda, J. Rego, J. Rino. Stereotactic
Anatomy of the Human Locus Ceruleus. 16th Congress of the European Society for Stereotactic
and Functional Neurosurgery (ESSFN), Vienna, June 2004.
Fonseca, T., Gaspar, H., Gonçalves, C., Neto, L., Gonçalves Ferreira, A.J. Estudo Comparado
Anatomia/IRM do Volume do Hipocampo Humano Normal. X Congresso Luso-Brasileiro de
Anatomia, Porto, October 2004.
Gonçalves Ferreira, A.J., P.S. Fernandes, H. Cardoso, B. Miranda, J. Rego, J. Rino. Anatomia
Estereotáxica do Locus Ceruleus Humano. Reunião da Sociedade Portuguesa de Neurocirurgia,
Estoril, May 2004.
Sousa Fernandes, P., Rego, J., Cardoso, H., Miranda, B., Gonçalves Ferreira, A.J. Estudo da
Anatomia Estereotáxica do Locus Ceruleus Humano Normal. X Congresso Luso-Brasileiro de
Anatomia, Porto, October 2004.
Castanhinha, S., Gonçalves, S., Santos, C., Gonçalves Ferreira, A.J. Veias Cerebral Interna e
Cerebral Magna – Anatomia Microcirúrgica dos Afluentes Cisternais. X Congresso Luso-
Brasileiro de Anatomia, Porto, October 2004.
Gonçalves Ferreira, A.J. Coordinator of Anatomy and Regent of the disciplines of Normal
Anatomy and Neuroanatomy of the Medicine Course, Faculdade de Medicina da Universidade de
Lisboa (FML)
Gonçalves Ferreira, A.J. Invited Professor of Anatomy, Faculdade de Farmácia da Universidade

de Lisboa.
Gonçalves Ferreira, A.J. Professor of Neuroanatomy of the Masters Degrees in Neuroscience,

Neuroftalmology, Sexology and Forense Medicine, Faculdade de Medicina da Universidade de
Lisboa.
Gonçalves Ferreira, A.J. Tutor of Undergraduate and Master Students, Faculdade de Medicina da
Universidade de Lisboa.
Gonçalves Ferreira, A.J. Professor of the European Research and Training Courses of the
European Association of Neurosurgical Societies (EANS)
Gonçalves Ferreira, A.J. Lecture on “Microsurgical Anatomy of Corpus Callosum”. Curso

Prático da Sociedade Portuguesa de Neurocirurgia, Hospital Egas Moniz, March 2004.
Gonçalves Ferreira, A.J. Lecture on “Erro de Descartes, de A. Damásio”. Biblioteca da Câmara

Municipal de Oeiras, 24 November 2004.

EEG/Sleep Laboratory
Peralta, R. et al. (2004) Alterações da Excitibilidade Neuromuscular na Hipocaliémia Iatrogénica.

Sinapse 4(1):69.
Coelho, M., Ferreira, J., Peralta, R., Biscoito, L., Albuquerque, L.(2004) Siderose Superficial do
Sistema Nervoso Central. Sinapse 4(2):93.
Souza, J.C., Paiva,T., Reimão, R. (2004) Somnolence and Accidents Involving Truck Drivers in
the Brazilian State of Mato Grosso do Sul. – Arquivos de Neuro-Psiquiatria – Jornal Oficial da
Academia Brasileira de Neurologia (Supl 2) Vol. 62:105, São Paulo, October 2004.
Souza, J.C., T. Paiva; R. Reimão (2004) Hábitos de Sono, Sonolência e Acidentes em

Caminhoneiros. Associação Paulista de Medicina – Conselho Nacional de Desenvolvimento
Cientifico e Tecnológico, 54-60.
Books/Book Chapters
Paiva, T. (2004) “Sleep and Headache”. In: Second volume, Handbook of Clinical Neurology
(HCN) 3rd edition, 15 september 2004.
Bentes, C., J. Costa, R. Santos, J.P. Foreid, V. Rolo, I. Pavão, T. Paiva: Ictal Singing as na
Epileptic Automatism. International Congress of the Cuban Society of Clinical Neurophysiology,
Havana, March 2004.
Bértolo, H. Visual Dream Content, Graphical Representation and EEG Alpha Activity in
Congenitally Blind Subjects. International Congress of the Cuban Society of Clinical
Neurophysiology, Cuba, 2004.
Peralta, A.R., Canhão, P., Macor, C. Collet Syndrome – Another Representation of Cerebral
Venous Thrombosis. (Poster) “European Neurological Society, July 2004.
Souza, J.C., T. Paiva: Sono, Hábitos, Qualidade de Vida e Acidentes em Camionistas do Brasil e
de Portugal. (Oral Communication) VI Congresso Brasileiro de Psicologia do Trânsito, 10-13
November 2004.
Bentes, C. Epileptogénese. IV Curso pós-graduado sobre Epilepsias. Lisboa, January 2004.
Bentes, C. Cirurgia da Epilepsia no HSM. A . Gonçalves Ferreira, Grupo da cirurgia da epilepsia

do HSM. 16º Encontro Nacional Epileptologia. Lisboa, March 2004.
Bértolo, H. A Importância da Luz nos Ciclos Circadiários. XVIII Congresso Internacional de

Optometria e Contactologia, Lisboa, Portugal, 2004.
Coelho, M., Ferreira, J., Peralta, R., Biscoito, L., Albuquerque, L.Siderose Superficial do Sistema
Nervoso Central. Congresso da Sociedade Portuguesa de Neurologia. November 2004.
Peralta, A.R., Mamede de Carvalho, Sá, J. Alteração da Excitabilidade Neuromuscular na

Hipocaliémia Iatrogénica. (Brief Communication) Fórum de Neurologia, Luso, May 2004.
Pimentel, J., F. Pinto, C. Bentes, Grupo da Cirurgia da epilepsia do HSM. Reunião da LPCE
sobre Problemas e Futuro da Cirurgia da Epilepsia em Portugal, Luso, July 2004.
Bentes, C. II Reunião do Núcleo de Estudos das Doenças Cerebrovasculares do HDS. Santarém,

June 2004.
Bentes, C. Os novos antiepilépticos no tratamento da epilepsia. Forúm de Epilepsia: A Epilepsia

ao Longo da Vida. Évora, June 2004.
Bentes, C. Epilepsia Pós AVC. 5º Simpósio do Núcleo de Estudos da Doença Vascular Cerebral,
Lisboa, November 2004.
Bértolo, H. Imagens Oníricas em Cegos. Programa Escola Aberta, Escola Secundária Inês de
Castro, Alcobaça, 2004
Gonçalves, M. O Sono no Idoso. Serviço de Psicogeriatria - Hospital de Magalhães Lemos,

OPorto, 27 January 2004.
Gonçalves, M. Curso de Perturbações do Sono. Caramulo, for General Practitionners, 17-18

April 2004.
Gonçalves, M. Perturbações do Sono, XIII Jornadas de Saúde de Aveiro, April 2004.
Gonçalves, M. Perturbações do Sono. Organised by Sub região de Saúde de Braga, to General

Practiotionners, 23-30 September 2004.
Paiva, T. WHO – Technical Meeting on Sleep Disturbance and Health, organised by World
Health Organization Regional Office for Europe, Bonn, Germany, 22-24 January 2004.
Paiva, T. O Efeito do Sono na Sinistralidade Rodoviária. Workshop - “Segurança Rodoviária –

Uma perspectiva da Mudança”, organised by Direcção Geral de Viação, 5 March 2004.
Paiva, T. Fisiologia do Sono e dos Sonhos. 1º Simpósio Internacional de Sono do Mato Grosso
do Sul – 6º Simpósio de Sono da Região do Pantanal, 14 April 2004.
Paiva, T. Sono e Acidentes Automotivos. 1º Simpósio Internacional de sono do Mato Grosso do

Sul – 6º Simpósio de Sono da Região do Pantanal, 14 April 2004.
Paiva, T. Perturbações do Sono. XIII Jornadas de Saúde de Aveiro, organised by Sub-Região de

Saúde de Aveiro, 29-30 April 2004.
Paiva, T. Meeting of Presidents of National Sleep Societies and ESRS , 2-4 April 2004
Paiva, T. Aspectos Neurofisiológicos Normais e Anormais do Sono. IV Curso Teórico-Prático de

Neurofisiologia Clínica, Hotel Riviera, Carcavelos, 8-10 May 2004.
Paiva, T. President “Lição de Encerramento”. IV Curso Teórico-Prático de Neurofisiologia

Clínica, Hotel Riviera, Carcavelos, 8-10 May 2004.
Paiva, T. Fatigue and Sleep Disorders. Annual European Congress of Rheumatology “EULAR
2004”, Berlin, Germany, 9-12 June 2004.
Paiva, T. Workshop Session 4A – How far do Cultural Differences Influence Clinical

presentation of Impaired Alertness? Second International Sleep Disorders Forum – The Art of
Good Sleep, Paris, France 10-12 September 2004.
Paiva, T. Workshop Vigilidade e Sono: Impacto na Segurança e Acidentes. Organised by

Direcção Geral de Transportes Terrestres, Lisboa, 12 October 2004.
Paiva, T. Morbilidade, Mortalidade e Saúde Pública do SAOS. Congress organised by Centro de

ORL, Hospital da CUF Infante Santo, Hospital da CUF, 22-23 October 2004 .
Paiva, T. Algumas Controvérsias em Epilepsia. Moderadora: “EEH Tratar ou não Tratar?”

Reunião Conjunta das Consultas de Epilepsia da Região Sul, Auditório Professor Almeida Lima,
Serviço de Neurologia, piso 7 Hospital de Santa Maria, 5 November 2004.
Paiva, T. Enxaqueca. VIII Jornadas COFANOR - “A mulher e a Saúde” na Fundação António de

Almeida, Oporto, 12 November 2004
Paiva, T. Mesa Redonda Horários e Ritmos: Redifinir o Normal. Congresso de Neurologia 2004,
organised by Sociedade Portuguesa de Neurologia, Hotel Solverde, Praia da Granja, 25-28
November 2004.
Pimentel, J., F. Pinto, C. Bentes. A cirurgia da epilepsia no HSM. Grupo da cirurgia da epilepsia
do HSM. Reunião da LPCE sobre Problemas e Futura da Cirurgia da Epilepsia em Portugal,
Luso, July 2004.
Bentes, C. 16º Encontro Nacional de Epileptologia, Lisboa, March 2004.

Master ‘s Degree Course
2005/07 T. Paiva: Organizer and coordinator of the 1st Master Degree in Sleep Medicine,
Faculdade de Medicina de Lisboa, 2004-05. This Master Degree course has
started with 18 students, selected after a selection phase (15 rejected). The course
aims to provide theoretical and practical background in the field.
Diploma Thesis (Teses de Licenciatura)
Two members of the group are (Teresa Paiva and Helder Bértolo) are actively involved in the
coordinating committee of the Course on Biomedical Engineering, organized by the Technical
University of Lisbon together with the Medical Faculty.
Furthermore, Teresa Paiva is responsible for a semestral discipline of the 3rd year: Temas de
Fronteira entre a Engenharia e a Medicina” and shares the discipline “Instrumentation” in the 4th
year.
Bentes, C. Reuniões de Formação em Epilepsia para Clínicos Gerais e outros Médicos não
neurologistas da região sul do País, no âmbito da LPCE. January to October 2004.
Bentes, C. Reuniões de Formação e Esclarecimento para cuidadores (Pais e Professores) e

doentes com epilepsia da região sul do País, no âmbito da LPCE. January to October 2004.
Paiva, T. Reunião de trabalho “WFSRS 2008/2010” nas instalações do Turismo de Lisboa, 9

November 2004.
Bentes, C. Reunião das Consultas de Epilepsia da Região Sul, November 2004.
Public Perception of Science and Disorder´s Awareness
Paiva, T. “O Efeito do Sono na Sinistralidade Rodoviária”. Workshop on “Segurança Rodoviária

– Uma perspectiva da Mudança”, promoted by Direcção Geral de Viação, 5 March 2004.
Paiva, T. Interview to the Journal O PÚBLICO entitled “Portugueses Dormem Cada Vez
Menos”, 14 March 2004.
Paiva, T. Press conference during the International Brain Awareness Week entitled “Dormir
Bem, Viver Melhor”, 16 March 2004.
Paiva, T. Interview to Joana Filipe for the Journal O PÚBLICO entitled “Fibromialgia e
Síndrome da Fadiga Crónica”, 17 March 2004.
Paiva, T. Interview to Teresa Martins for the CADERNOS DE SAÚDE PÚBLICA entitled
“Dormir Pouco é Hipotecar o Futuro”, April 2004.
Paiva, T. Revision of an article published in the magazine MEN’S HEALTH about

“Hipertensão”, April 2004.
Paiva, T. “The First Meeting of the Sleep Medicine Committee”, Copenhagen, 28-30 May 2004.
Paiva, T. Interview to the magazine AUTOMOTOR entitled “Acidentes e Sono”, June 2004.
Paiva, T. Interview to Sofia Jesus for the Journal DN entitled “Fibromialgia e Síndrome da
Fadiga Crónica”, 12 August 2004.
Paiva, T. Publication of an article in the magazine COREDES – REGIÃO NORTE MS –

Conselho Regional de Desenvolvimento da Região Norte, Mato Grosso do Sul, Brazil, about the
Pos - Doc. Thesis of Prof. José Carlos Souza, 23 August 2004.
Paiva, T. Invited to participate in the programme “ENCONTRO MARCADO” presented by Rita

Ferro Rodrigues , on SIC MULHER, 20 October 2004.
Paiva, T. Interview to the magazine PÚBLICA entitled “2 Horas de Sonho por Sono”,
November 2004.
Paiva, T. Interview to the magazine MEDICINA & SAÚDE entitled “Alguns Medicamentos
Podem Perturbar o Sono”, November 2004.
Paiva, T. Interview to Clara Soares, entitled “Segurança Rodoviária e Sono pesado – Estudo
Revela que os Camionistas portugueses Guiam Ensonados”, November 2004.
Paiva, T. Interview to the Journal A CAPITAL entitle “Os Guardadores do Sono”, 6 December
2004.
Paiva, T. Workshop “Perturbações do Sono – O que é o Sono?” at Escola Secundária José

Gomes Ferreira, with the support and scientific review of Prof. Teresa Paiva, Programa Health in
the XXI Century a vision from the European Youth.
Paiva, T. Workshop “Perturbações do Sono – Precisamos de Dormir?” at “Escola Secundária

José Gomes Ferreira, with the support and scientific review of Prof. Teresa Paiva, Programa
Health in the XXI Century a vision from the European Youth.
Autonomic Nervous System Unit
Teles-Martins, E. (2004) Ser médico. The Physician and Sportsmedicine (6):1. (Ed.Portuguesa.)
Teles-Martins, E. (2004) O exercício em idosos – uma moda benéfica a promover. The Physician
and Sportsmedicine (6):2. (Ed. Portuguesa)
Teles-Martins, E. (2004) O médico face à síndrome do coração do atleta. The Physician and
Sportsmedicine (6):3. (Ed Portuguesa)
Books/Books Chapters
Silva-Carvalho, L. (2004) The study of circulation at the Institute of Physiology. Circulation,

Almeida, A., Rolão, C., Araújo, F., Rego, F., David, C., Vagueiro, M.C., Ducla-Soares, J.L.
Alterações da microcirculação miocárdica na drepanocitose : estudo de ecocardiografia de
contraste miocárdio. XXV Congresso Português de Cardiologia, March 2004 and published in
the Revista Portuguesa de Cardiologia, Vol.23.
Araújo, F., Garcês, S., Rolão, C., Rego, F., Ducla-Soares, J.L. Síndroma de taquicardia postural.
Um caso clinico. XXV Congresso Português de Cardiologia, March 2004 and published in the
Revista Portuguesa de Cardiologia, Vol.23.
Carvalho, F.A., Ducla Soares, J.L., Maria, A.V., Guerra, J., Martins Prata, M., Caeiro, L., Martins
Silva, J., Saldanha, C. Study of nitric oxide mobilization after erythrocytes stimulation with
acethilcoline on healthy and patient persons. 23rd European Conference on Microcirculation,
September 2004.
Garcês, S., Araújo, F., Rolão, C., Rego, F., Ducla-Soares, J.L. POTS and LQTS: Just a
Coincidence? First Joint Meeting of the European Federation of Autonomic Societies &
American Autonomic Society, Amsterdam, Netherlands, October 2004.
Gonçalves, V. Alterações Cromossómicas em Doentes com Meningiomas. Congresso Brasileiro

de Neurocirurgia, September 2004.
Gonçalves, V. Hemangioferricitomas Intra-raquidianos - 4 casos clínicos. XXV Congresso

Brasileiro de Neurocirurgia, September 2004.
Pinto, B.G., Bettencourt, M.J., Silva Carvalho, L. Autonomic dysfunction in essential

hypertension with orthostatic diziness. A target for selective treatment..XXV Congresso
Português de Cardiologia, March 2004 and published in the Revista Portuguesa de Cardiologia,
Vol.23.
Postolache, G., Rocha, I., Postolache, O., Silva-Carvalho, L., Girão P. A wavelet based approach
for monitoring baroreceptors function test in rats. Proceedings of IMTC, Como, Italy, May 2004.
Postolache, G., Silva-Carvalho, L., Postolache, O., Girão, P., Rocha, I. (2004) HRV and BPV
neural network model with wavelet based algorithm calibration. Proceedings of IMEKO TC-4,
13th International Symposium on Measurements for Research and Industry Applications and the
9th European Workshop on ADC Modelling and Testing, Vol.2, 451-456, Athens, Greece,
September 2004.
Rosário, L., Rocha, I., Silva Carvalho, L. Central angiotensin regulates left ventricle function and
vascular response to acute myocardial ischemia. 1st Annual Symposium of the AHA Council on
Basic Cardiovascular Sciences. “Stress Signals, Molecular Targets and the Genome”, Stevenson,
Washington, July 2004.
Victor, A.R., Brás-Rosário, L., Oliveira, A.R., Aurélio, M., Carvalho, H., Dias, M., Carrageta, M.
Dinâmica da estenose mitral: contribuição do estudo cor modo M. XXV Congresso Português de
Cardiologia, March 2004 and published in the Revista Portuguesa de Cardiologia, Vol.23.
Araújo, F., Rolão, C., Garcês, S., Costa Santos, J.M., Fernandes, A., Rego F., Ducla Soares, J.L.
Mielodisplasia com mielofibrose. Indicação para corticoterapia?. 10º Congresso Português de
Medicina Interna, May 2004.
Araújo, F., Rolão, C., Garcês, S., Rego, F., Ducla Soares, J.L. Púrpura trombocitopénia
trombótica e lupus. 10º Congresso Português de Medicina Interna, May 2004.
Dias, J., Aurélio, M., Carvalho, H., Rosário, L., Silva Carvalho, L., Rocha, I. A tangible interface
for augmented reality visualization in 4D echocardiography imaging of the left ventricle of the
heart.. “Interacção 2004”, Departament of Mathematics, Faculty of Sciences of Lisbon, May
2004.
Garcês, S., Araújo, F., Rolão, C., Rego, F., Ducla Soares, J.L. Tromboses venosas recorrentes
devidas a factor VIII elevado. 10º Congresso Português de Medicina Interna, May de 2004.
Gomes-Pinto, B., Bettencourt, M.J., Silva-Carvalho, L. A disfunção autonómica na hipertensão

essencial com tontura ortostática, alvo da estratégia terapêutica. Meeting of the Portuguese
Society of Hypertension and published at Livro de Resumos SPH, February 2004.
Gonçalves, V. Anatomia cirúrgica do ângulo ponto-cereboloso. VIII Curso Português de

Neurocirurgia. March 2004.
Gonçalves, V. Hemangioferricitomas Intra-raquidianos - 4 casos clínicos. XXV Congresso

Brasileiro de Neurocirurgia. September 2004.
Gonçalves, V. Indicações Cirúrgicas em Hemorragias Subaracnóideias. Reunião Clínica do

Hospital de S. José, October 2004.
Gonçalves, V. Terapêutica Operatória em Aneurismas Cerebrais. Reunião Clínica do Hospital de

S. José, November 2004.
Lopes, A.M., Morgado, M.J. Pedro, L.M. Ducla Soares, J.L. Trombose da mesentérica em
individuo jovem. 10º Congresso Português de Medicina Interna, May 2004.
Marques, N., Vale Trancas, D., Dâmaso, C., Araújo, F., Ducla Soares, J.L. Infecções e
antibioterapia num serviço de medicina. 10º Congresso Português de Medicina Interna, May
2004.
Morgado, M.J., Fernades, J., Lopes, A., Ducla Soares, J.L. Lesões disseminadas do SNC- um caso
de tuberculose em doente imunocompetente. 10º Congresso Português de Medicina Interna, May
2004.
Rolão, C., Araújo, F., Garcês, S., Simões, R., Rego, F., Ducla Soares, J.L. Manifestações
sistémicas na drepanocitose). 10º Congresso Português de Medicina Interna, May 2004.
Teles-Martins, E. O exercício físico como elemento central da prevenção cardiovascular.

Fundação Portuguesa de Cardiologia, May 2004.
Teles-Martins, E. Tratar a hipertensão arterial para além do controlo da pressão arterial,

January 2004.
Teles-Martins, E. Insuficiência cardíaca: aspectos da avaliação funcional e terapêutica. Jornadas

de Cardiologia do HMP, May 2004.
Teles-Martins, E. Heart failure: treatment aims and drugs effects. Jornadas de Cardiologia do
HDSetubal, May 2004.
Teles-Martins, E. Ambientes extremos – o aparelho cardiovascular e o ambiente hiperbárico.

Jornadas do HMP Lisbon, May 2004.
Teles-Martins, E. Para lá da pressão arterial... a lesão dos órgãos alvo. Jornadas do HMP,
Lisbon, October 2004.
Silva-carvalho, L. organised the Seminar Adenosine effects upon the nucleus tractus solitarius by
Nuno Félix, January 2004.
Silva-Carvalho, L. organised the Seminar Gross anatomy of the ocular circulation and its
implications on eye physiology and pharmacology by Esmeralda Delgado, March 2004.
Silva-Carvalho, L. organised the Seminar Wavelets and autonomic function by Gabriela

Postolache, May 2004.
Rocha, I. organised the Seminar Shock and autonomic nervous system: a review by Nuno Felix,
September 2004.
Rocha, I. organised the Seminar Cerebral infarction and urinary bladder function, by José Santos
Dias, November 2004.
Silva-carvalho, L. organised the Seminar Physiology of ocular circulation by Carlos Marques

Neves, December 2004.
Ducla-Soares, J. Diabetes e disautonomia (Diabetes and disautonomy). Meeting of SPSNA,

January 2004.
Silva-Carvalho, L. Physiology and variability. “ Lunch time seminars”, Departmento de

Matemática, Faculdade de Ci~encias da Universidade de Lisboa, November 2004.
Silva-Carvalho, L. Controlo integrado cardiorespiratório (cardiorespiratory regulation). Meeting

of SPSNA, January 2004.
Brás Rosário, L. Portuguese Congress of Cardiology, March 2004.
Ducla Soares, J. Meeting of the Portuguese Society of Autonomic Nervous System, January 2004.
Silva-Carvalho, L. Meeting of the Portuguese Society of Autonomic Nervous System, January

2004.
Master’s in Neurosciences
Sensory Physiology (module)
Physiology of Autonomic nervous systems (module)
Pathology of the autonomic nervous system (module)
Master’s in Bioethics
Bioethics and physiology research
Gonçalves, V. Anatomia cirúrgica do ângulo ponto-cereboloso. VIII Portuguese Course on

Neurosurgery, March 2004.
Thesis Completed
PhD Thesis
Carlos Marques Neves (2004) “Influências Autonómicas na Circulação Ocular – Efeito da

Activação de Áreas Bulbares e Estudos no Domínio da Frequência”. (Autonomic control of
ocular circulation: role of brainstem areas and studies on the frequency domain), Faculdade de
Medicina da Universidade de Lisboa. Supervisor: L. Silva-Carvalho.
Victor Gonçalves (2004) “Cerebelo e Regulação Cardiovascular”(Cerebellum and cardiovascular

regulation), Faculdade de Medicina da Universidade de Lisboa. Supervisor L. Silva-Carvalho.
Luis Brás Rosário (2004) “A Disautonomia do Enfarte Agudo do Miocárdio e o Sistema

Angiotensina Central” (Disautonomy on the acute miocardial infarction), Faculdade de Medicina
da Universidade de Lisboa. Supervisor: L.Silva-Carvalho.
Master Thesis
Nuno Félix (2004) “Efeitos da Injecção de Adenosina no Núcleo do Tracto Solitário em Rato”
(Adenosine role at NTS level), Faculdade de Medicina da Universidade de Lisboa. Supervisor: L.
Silva-Carvalho.
Diploma Thesis
Inês Maia Liberato (2004) “Registo da Actividade Celular na Área de Defesa Hipotalâmica –
Convergência da Informação com Origem nos Baroreceptores Aórticos e Receptores Cardíacos”
(Recording of celular activity at hypothalamic defence area- convergency of inputs with origin in
the aortic baroreceptores and cardiac receptors), Undergraduate Thesis in Biotechnological
Engineering, Universidade Lusófona de Humanidades. Supervisor: I. Rocha

Cerebrovascular Diseases Group
Calado, S., Oliveira, V., Viana-Baptista, M., Ferro, J.M. (2004) Long-term prognosis of carotid
and vertebral artery dissection. Sinapse 4:21-27.
Oliveira, V. (2004) Egas Moniz revisitado (O politico). Sinapse 1:45-49.
Oliveira, V. (2004) Egas Moniz revisitado (O homem de ciência). Sinapse 2:55-58.
Ferro, J.M. (2004) Implementação de Unidades de AVC. Rev Port Cardiol 23:1245-1247.
Books/Book Chapters
Ferro JM, Pinto F. Semiologia Neurológica, 2004.
Basile, A.M., Pantoni, L., Simoni, M., Erkinjuntti, T., Waldemar, G., Ferro, J.M., Inzitari, D.
Age-related white matter changes predict quality of life in independent elderly patients. The
leukoaraiosis and disability project. (Oral Communication) 8th Congress of the European
Federation of Neurological Societies, Paris, France, 4-7 September 2004 .
Caeiro, L., Ferro, J.M., Albuquerque, R., Figueira, M.L. Apathy in acute stroke patients. (Oral
Communication) 13th European Stroke Conference, Mannheim-Heidelberg, Germany, 12-15 May
2004.
Caeiro, L., Ferro, J.M., Albuquerque, R., Figueira, M.L. A study of the suicide thoughts in acute
stroke patients. (Poster) 13th European Stroke Conference, Mannheim-Heidelberg, Germany, 12-
15 May 2004.
Canhão, P., Cortesão, A., Cabral, M., Ferro, J.M., Stam, J., Bousser, M.G, Barinagarrementeria,
F. on behalf of the ISCVT Collaborators. Are steroids useful for the treatment of cerebral venous
thrombosis? ISCVT results. (Oral Communication) 13th European Stroke Conference,
Mannheim-Heidelberg, Germany, 12-15 May 2004.
Corea, F., Deepalque, D., De Reuck, J., Ferro, J.M., Schmidt, R., Mas, J.L., Leys, D., Parnetti, L.,
Gallai, V. Silent cerebral infarction in cardioembolic stroke: prevelance and associated factors
on the SAFE II Study population. (Oral Communication) 13th European Stroke Conference,
Costa, J., Ferro, J.M., Matias-Guiu, J., Alvarez-Sabin, J., Torres, F. Triflusal for preventing
serious vascular events in people at high risk. (Poster) 13th European Stroke Conference,
Ferro, J.M., Canhão, P., Stam, J., Bousser, M.G., Barinagarrementeria, F on behalf of the ISCVT
Investigators. Cerebral vein and dural sinus thrombosis in patients over the age of 65. (Oral
Communication) 13th European Stroke Conference, Mannheim-Heidelberg, Germany, 12-15 May
2004.
Girot, M., Ferro, J.M., Canhão, P., Bousser, M.G., Barinagarrementeria, F., Stam, J. for the
ISCVT Collaborators. Outcome in patients with cerebral venous thrombosis and intracerebral
haemorrhage treated by anticoagulation. Results of International Study on Cerebral Vein and
Dural Sinus Thrombosis. (Oral Communication) 14th Meeting of the European Neurological
Society, Barcelona, Spain, 26-30 June 2004.
Madureira, S., Verdelho, A., Ferro, J.M. The influence of demographic variables in the
neuropsychological performance of an independent elderly population with cerebral white matter
changes – the LADIS (leukoaraiosis and disability) study. (Poster) 8th Congress of the European
Federation of Neurological Societies, Paris, France, 4-7 September 2004.
Pantoni, L., Basile, A.M., Simone, M., Erkinjuntti, T., Waldemar, G., Ferro, J.M., Inzitari, D. on
behalft of the LADIS Study Group. Age-related white matter changes predict hidden global
function impairment in elderly people. The LADIS (Leukoaraiosis and Disability in the Elderly)
Study. (Oral Communication) 13th European Stroke Conference, Mannheim-Heidelberg,
Germany, 12-15 May 2004.
Peralta, R., Canhão, P., Macor, C. VII-XII cranial nerves palsis – another presentation of
cerebral vein thrombosis. (Poster) 14th Meeting of the European Neurological Society, Barcelona,
Spain, 26-30 June 2004.
Santos, C., Caeiro, L., Ferro, J.M., Albuquerque, R., Figueira, M.L. Anger, hostility and
aggression in the first days of acute stroke. (Oral Communication) 13th European Stroke
Conference, Mannheim-Heidelberg, Germany, 12-15 May 2004.
Caeiro, L., Ferro, J.M., Albuquerque, R., Figueira, M.L. Um estudo dos pensamentos suicidas nos
doentes com AVC agudo. (Oral Communication) Forum de Neurologia 2004, Luso, Portugal, 20-
23 May 2004.
Calado, S., Oliveira, V., Viana-Baptista, M., Ferro, J.M. Dissecção arterial carotídea e vertebral
– estudo de seguimento a longo prazo. (Oral Communication) Forum de Neurologia 2004, Luso,
Portugal, 20-23 May 2004.
Canhão, P., Cortezão, A., Cabral, M., Ferro, J.M., Stam, J., Bousser, M.G., Barinagarrementeria,
F. Será útil usar corticóides no tratamento das tromboses venosas cerebrais? Resultados do
ISCVT. (Oral Communication) Forum de Neurologia 2004, Luso, Portugal, 20-23 May 2004.
Couto, M., Correia Guedes, L., Ruivo, J., Canhão, P., Pinho e Melo, T., Ferro, J. Craniectomia
descompressiva em doente com trombose venosa cerebral. (Oral Communication) Congresso de
Neurologia 2004, Algarve, Portugal, 25-28 November 2004.
Ferro, J.M., Canhão, P., Bousser, M.G., Stam, J, Barinagarrementeria, F. e os investigadores do

ISCVT. Tromboses dos seios durais em doentes com mais de 65 anos. (Oral communication)
Forum de Neurologia 2004, Luso, Portugal, 20-23 May 2004.
Geraldes, R., Canhão, P. Parésia dos movimentos oculares verticais e nistagmo de convergência
– retracção em doentes com acidente vascular cerebral isquémico da protuberância. (Oral
Communication) Forum de Neurologia 2004, Luso, Portugal, 20-23 May 2004.
Paiva Nunes, A., Albuquerque, L., Biscoito, L., Ferro, J. Fibrinólise local em trombose venosa
cerebral: caso clínico. (Oral Communication) Congresso de Neurologia 2004, Algarve, Portugal,
25-28 November 2004.
Santos, C., Caeiro, L., Ferro, J.M., Albuquerque, R., Figueira, M.L. Lateralidade dos sintomas de
doentes com diagnóstico psiquiátrico internados numa unidade de AVC. (Oral Communication)
Forum de Neurologia 2004, Luso, Portugal, 20-23 May 2004.
Canhão, P. Evidencias y opciones en el tratamiento de las trombosis venosas durales. XX

Seminário Nacional Neurológico de Invierno, Candanchú, Spain, 5 February 2004.
Ferro, J.M. Treatment of cerebral venous thrombosis. Gratz, Austria, 15 January 2004.
Ferro, J.M. Cerebral venous thrombosis past, present and future. 7th meeting of the Austrian
Stroke Society, Klagenfurt, Austria 16 January 2004.
Ferro, J.M. Variabilidad de la presentación clínica de las trombosis venosas durales. XX

Seminário Nacional Neurológico de Invierno, Candanchú, Spain 5 February 2004.
Ferro, J.M, Melo, T.P. Prespectivas do tratamento actual do AVC agudo. Sessão Clínica.
Hospital do Espirito Santo, Évora, 19 February 2004.
Ferro, J.M. AVC e depressão: do diagnóstico ao tratamento. 2º Fórum de Neurociências. Lisboa,

27 March 2004.
Ferro, J.M. Prevenção dos acidentes cerebro-vasculares. VI Congresso Médico Nacional dos
Hospitais Distritais, Troia, 30 April 2004.
Ferro, J.M. Cerebral venous thrombosis. Postgraduate Clinical Neurosciences Teaching

Programme, Cambridge, England, 8 June 2004.
Ferro, J.M. Cerebrovascular disorders. Case Discussions with Experts. 14th Meeting European
Neurological Society, Barcelona, Spain, 26 June 2004.
Ferro, J.M. Anti-aggregation and blood pressure. 23rd European Conference on microcirculation.
Lisboa, 10 September 2004.
Ferro, J.M. AVC. Curso livre de Geriatria, Lisboa, 29 September 2004.
Ferro, J.M. Via verde dos AVCs. Jornadas do Internato Médico da Feira, Sta Maria da Feira, 27
November 2004.
Oliveira, V. TACIP Study. 23rd European Conference on microcirculation. Lisboa, 10 September

2004.
Oliveira, V. 23rd European Conference on microcirculation. Microcirculation and vascular

biology: a basis for research and a reason for life. Lisboa, 8-11 September 2004.
Caeiro, L. “Problemas psicológicos e comportamentos. Actualização no tratamento dos doentes

com AVC agudo”. Faculdade de Medicina, Lisboa, 23 March 2004.
Canhão, P. “Tratamento agudo: anticoagulação e antiagregação. Actualização no tratamento dos

doentes com AVC agudo”. Faculdade de Medicina, Lisboa, 23 March 2004.
Canhão, P. “Escalas de avaliação do doente com AVC. Actualização no tratamento dos doentes
com AVC agudo”. Faculdade de Medicina, Lisboa, 24 March 2004.
Canhão, P. “Consulta de AVC, objectivos e funcionamento. Actualização no tratamento dos

Falcão, F. “Tratamento agudo: medidas gerais. Actualização no tratamento dos doentes com AVC
agudo”. Faculdade de Medicina, Lisboa, 23 March 2004.
Falcão, F. “Tratamento agudo: prevenção e tratamento de complicações. Actualização no

tratamento dos doentes com AVC agudo”. Faculdade de Medicina, Lisboa, 23 March 2004.
Ferro, J.M. “Coma e estado vegetativo persistente”. V Mestrado em Bioética, Faculdade de

Medicina da Universidade de Lisboa, Lisboa, Portugal, 12 June 2004
Ferro, J.M. “AVC no idoso”. I Curso Pós-Graduado – Actualização em geriatria. Escola Superior
de Enfermagem Calouste Gulbenkian, Lisboa, 19 March 2004
Ferro, J.M. “Epidemiologia de AVC em Portugal e no Hospital de Santa Maria. Actualização no

tratamento dos doentes com AVC agudo”. Faculdade de Medicina, Lisboa, 22 March 2004.
Ferro, J.M. “Via verde para o AVC e cuidados pré-hospitalares. Actualização no tratamento dos
Ferro, J.M. “Avaliação clínica na fase hiperaguda. Actualização no tratamento dos doentes com
AVC agudo”. Faculdade de Medicina, Lisboa, 22 March 2004.
Ferro, J.M. “Bioética e a pedagogia em Neurologia”. Mestrado de Bioética. Faculdade de

Medicina, Lisboa, 16 April 2004.
Ferro, J.M. “Venous thrombosis. Teaching Course – Less common causes of stroke- revisited”.
13th European Stroke Conference, Mannheim, Germany, 12 May 2004.
Ferro, J.M. “Management of acute stroke patients. Teaching Course – Acute stroke – Un update”.
Paris, France, 4 September 2004.
Melo, T.P. “Tratamento agudo: trombólise. Actualização no tratamento dos doentes com AVC
Melo, T.P. “Organização da Unidade de AVC. Actualização no tratamento dos doentes com AVC
agud”o. Faculdade de Medicina, Lisboa, 24 March 2004.
Oliveira, V. “Morte Cerebral”. V Mestrado em em Bioética, Faculdade de Medicina da

Universidade de Lisboa, Lisboa Portugal, 12 June 2004
Oliveira, V. “Ultrassonografia na fase aguda. Actualização no tratamento dos doentes com AVC
Oliveira, V. “Doentes com AVC não internados na Unidade de AVC. Actualização no tratamento
dos doentes com AVC agudo”. Faculdade de Medicina, Lisboa, 25 March 2004.
Oliveira, V. “Consulta de anticoagulação. Actualização no tratamento dos doentes com AVC

Thesis completed
Master Thesis
Lara Isabel Pires de Melo Caeiro (2004) “Apatia no AVC agudo”. Tese de Mestrado em
Neurociências, Faculdade de Medicina da Universidade de Lisboa. Supervisor: J.M Ferro.

Language Research Laboratory
Castro-Caldas, A. (2004) O Contributo da Neuroimagiologia para o Diagnóstico e Tratamento

Fonoaudiológico. Pró-Fono Vol. 16, 1:3-5.
Castro-Caldas, A. O Conceito de Dominância Cerebral Revisitado. Re(abilitar)
Books/Book Chapters
Castro-Caldas, A. (2004) Existirá um Homem Neuronal? In: Consciência e Cognição.

Publicações da Faculdade de Filosofia – UCP, Braga, pp15-27.
Castro-Caldas, A. (2004) Neuropsicologia da Linguagem. In: Neuropsicologia Hoje, V.M.

Andrade, F.H. Santos e O. Bueno (Org), Editora Artes Médicas, São Paulo, pp 165-208.
Castro-Caldas, A. (2004) Power in the Framework of Cognitive Neuroscience. In: Power in

Focus: Perspectives from Multiple Disciplines. Subhash Durlabhji (Ed.) Wyndham Hall Press,
Lima, Ohio, pp 269-298.
Castro-Caldas, A. (2004) O Leucótomo. In: Circulação orgs: Faculdade de Medicina de Lisboa.
Martins, I.P. (2004) Persistent Acquired Childhood Aphasia. In: “Neurogenic Language
Disorders in Children”. Ed. Fabro F. “E.Medea” Scientific Institute, University of Udine.
Elsevier, pp. 231-251.
Castro-Caldas, A. Going to school in old age. First Congress of the European Neuropsychological
Societies, Modena, 2004.
Castro-Caldas, A. & Nunes, M. V. The knowledge of orthography and the organization of

working memory. (Poster 5) Universidade Lusófona – The Future of Mind and Behaviour
Sciences, Lisboa, March 2004.
Castro-Caldas, A. & Nunes, M. V., Maestú, F., Ortiz, T., Simões, R., Fernandes, R., Campo, P.,
Fernandez, A., Gonçalves, M. & Amo, C. Learning orthography in adult life: A
magnetoencephalography study. (Poster 6) Universidade Lusófona – The Future of Mind and
Behaviour Sciences, Lisboa, March 2004.
Cavaco, S., Anderson, S. & Castro-Caldas, A. Parameters of procedural memory in amnesia.

(Poster 7) Universidade Lusófona – The Future of Mind and Behaviour Sciences, Lisboa, March
2004.
Cavaco, S., Anderson, S.W, Castro-Caldas, A., Damasio, H. Focal basal ganglia damage and
procedural memory. 3rd joint meeting of the Australian Society for the Study of Brain
Impairment and International Neuropsychological Society, Brisbane, 7-10 July 2004.
Cavaco, S., Anderson, S.W., Rosa, B., Buchanan, T., Castro-Caldas, A., Damasio, H. Acquisition
of visuomotor skill and predictive eye-movements in amnesia. 34th Society for Neuroscience
Annual Meeting, San Diego, 23-27 October 2004.
Fernandes, R., Simões, R., Nunes, V., Gonçalves, M. & Castro-Caldas, A. Mirror writing and
literacy. (Poster 8) Universidade Lusófona – The Future of Mind and Behaviour Sciences,
Lisboa, March 2004.
Gil Gouveia, R., Wilkinson, P., Kaube, H. (2004) Severe hemiplegic migraine attack precipitatted
by fentanyl sedation for esophagogastroscopy. Cephalalgia 24(12):1099-1100.
Gonçalves, M. & Castro-Caldas, A. The influence of literacy in the B.O.R.B.’s performance.

(Poster 10) Universidade Lusófona – The Future of Mind and Behaviour Sciences, Lisboa, March
2004.
Lauterbach, M., Martins, I.P., Wilmes, K (2004) The influence of age, education and gender on
the performance in neuropsychological testing: normative data for the Aachen Aphasia Test
(AAT) in the portuguese version. Arquivos de Neuro-psiquiatria. Jornal Oficial da Academia
Brasileira de Neurologia 62 (suppl.2):4.
Lauterbach, M., Martins, I.P., Ferreira, A.C. (2004) A new aphasia test for the Portuguese
language. Introduction of the Aachen Aphasia Test (AAT) in the portuguese version: proving the
equivalence with the Lisbon Aphasia Battery (BAAL). Arquivos de Neuro-psiquiatria. Jornal
Oficial da Academia Brasileira de Neurologia 62 (suppl.2):5.
Lees, A., Gershanik, O., Blin, O., Behari, M., Otero, E., Ferreira, J., Aguillar, M., Kies, B.,
Castro-Caldas, A., Bodjarian, N, Rascol, O. Piribedil efficacy in monotherapy (150 to 300
mg/day) in the novo parkinsonian patients: planned 6-month analysis of the 2-year Parkison-
Regain study. AAN Congress, San Francisco, 2004.
Loureiro, C., Fernandes, T., Pavão Martins, I., Ferro, J. (2004) Behavioural Inattention Test:
Normative Data and the Need for a New Criterion. Journal of International Neuropsychological
Society Vol. 10, Issue S1: 107.
Simões, R., Fernandes, R., Nunes, M.V., Gonçalves, M., Martins, P. & Castro-Caldas, A.
Inability for tactile reading by poor writers and late schooled subjects. (Poster 16) Universidade
Lusófona – The Future of Mind and Behaviour Sciences, Lisboa, March 2004.
Albuquerque, L., Sá, J., Catonni, M.B., Morgado, C., Barroso, C (2004) Leucoencefalopatia
associada a metastização difusa de adenocarcinoma pulmonar. Sinapse, Publicação da Sociedade
Portuguesa de Neurologia 4(2):110.
Ferreira, S., Albuquerque, L., Leal, G., Martins, I.P. (2004) Características da fluência verbal
semântica e fonémica do adulto jovem: o lugar das pausas. Sinapse, Publicação da Sociedade
Portuguesa de Neurologia 4(2):113.
Fonseca, J., Rocha, L., Leal, R (2004) A história do Sr. Sommer. Análise linguística de um
discurso afásico. Sinapse, Publicação da Sociedade Portuguesa de Neurologia 4(2):111.
Gil-Gouveia, R., Costa-Reis, P., Martins, I.P., Parreira, E. (2004) Escala de sintomas cognitivos
na enxaqueca. Sinapse, Publicação da Sociedade Portuguesa de Neurologia 4(2):135.
Gil Gouveia, R., Sousa, R.F., Lopes, L., Campos, J., Martins, I.P. (2004) Cefaleias e
procedimentos endovasculares. Sinapse, Publicação da Sociedade Portuguesa de Neurologia
4(2):151
Gil Gouveia, R, Wilkinson, P, Kaube, H. (2004) Crise severa de enxaqueca hemiplégica

precipitada pela administração de fentanil para realização de endoscopia digestiva. Sinapse,
Publicação da Sociedade Portuguesa de Neurologia 4(2):124
Lauterbach, M., Martins, I.P., Aleixo, A.M. (2004) Não dizer coisa com coisa: análise de tipo de
erro em provas de nomeação. Sinapse, Publicação da Sociedade Portuguesa de Neurologia 4
(2):112.
Nunes, A.P., Albuquerque, L., Biscoito, L., Ferro, J. (2004) Fibrinólise local em trombose venosa
cerebral: caso clínico. Sinapse, Publicação da Sociedade Portuguesa de Neurologia 4(2):123.
Albuquerque, L. Gliomas de baixo grau dos hemisférios cerebrais. Reunião da Associação

Portuguesa de Neuro-oncologia, 2004.
Coelho, M., Ferreira, J.J., Dias, B., Sampaio, C., Martins, I.P., Castro-Caldas, A. Time
perception: effect of aging and parkinsonism. 5º Simposium da Fundação Bial "Aquém e Além
do Cérebro", Porto 2004.
Gil-Gouveia, R., Sousa, R.F., Lopes, L., Campos, J., Martins, I.P. Cefaleias e procedimentos
endovasculares. Reunião de Outono da Sociedade Portuguesa de Cefaleias, Óbidos, 5-6
November 2004.
Gil-Gouveia, R., Costa-Reis, P., Parreira, E., Martins, I.P. Escala de Sintomas Cognitivos na
Enxaqueca. Reunião de Outono da Sociedade Portuguesa de Cefaleias, Óbidos, 5-6 November
2004.
Ginó, S., Mendes, T., Guerreiro, M., de Mendonça, A. Metamemória e Esquecimento. Grupo de
Estudos do Envelhecimento, Óbidos, 2004.
Leal, G, Vasconcelos, M. Representação mental e acesso a formas regulares e irregulares: dados

de um paciente afásico falante nativo do português europeu. XX Congresso Nacíonal da
Associação Portuguesa de Linguística, 2004.
Loureiro, C., Fernandes, T., Martins, I.P., Ferro, J. Behavioural Inattention Test: Normative Data
and the Need for a New Criterion. 5º Simposium da Fundação Bial "Aquém e Além do Cérebro",
Porto, 2004.
Pérola, S., Ginó, S., Guerreiro, M., de Mendonça, A. Que horas são no teu relógio? O Teste do
Relógio como Instrumento de Avaliação Neuropsicológica. Grupo de Estudos do
Envelhecimento, Óbidos, 2004.
Castro-Caldas, A. Como se adapta o cérebro ao conhecimento da ortografia. Ciclo de Colóquios

Despertar para a Ciência 2004, Fundação Calouste Gulbenkian, Lisboa, 21 January 2004.
Castro-Caldas, A. O Futuro das Ciências da Mente e do Comportamento. Comentário à

conferência do Prof. Doutor Niels Birbaumer “The future of thought-translation”. Departamento
de Psicologia, Universidade Lusófona, Torre do Tombo, Lisboa, 25-27 March 2004.
Castro-Caldas, A. Moderador da sessão Depressão ou Demência: limites e sobreposições. CCB:

2º Forum de Neurociências, Lisboa, 27 March 2004.
Castro-Caldas, A. Membro do Comité Cientifico e Moderador da sessão Aquém e Além do

Cérebro. 5º Simpósio da Fundação Bial, Porto, 31 March – 2 April 2004.
Castro-Caldas, A. Presidência e Conferência Research and Development where is it Leading? 5th

Multi-disciplinary Conference of EPDA – European Parkinson’s Disease Association. FML -
Associação de Estudantes da FML: Saídas Profissionais em Neurologia, Lisboa 6-9 May 2004.
Castro-Caldas, A. Os processos neurobiológicos subjacentes ao conhecimento da matemática.

Ciclo Matemática, Ciências e Arte, Faculdade de Ciências da Universidade de Lisboa, 20 May
2004.
Castro-Caldas, A. Como se adapta o cérebro ao conhecimento da ortografia. Porto, 25 May

2004.
Castro-Caldas, A. Comité Científico, 2nd Lisbon Meeting on Language Acquistion. Faculdade de

Letras da Universidade de Lisboa, 1-4 June 2004.
Castro-Caldas, A. One brain for two languages. 4º Congresso Internacional da European Society
for Translation Studies - Doubts and Directions. Faculdade de Letras da Universidade de Lisboa,
28 September 2004.
Castro-Caldas, A. Prisioneiros do Próprio Cérebro. CADin, Cascais, 6 October 2004.

Castro-Caldas, A. Mente e Consciência: os caminhos cruzados da Filosofia, Psicologia e nas

Neurociências. Conferência: “O contributo das Neurociencias para a compreensão do Universo”,
UCP, Braga, 8 October 2004.
Castro-Caldas, A. Como se adapta o cérebro ao conhecimento da ortografia. Coimbra, 10

November 2004.
Castro-Caldas, A. Investigare. 1º Congresso Nacional do Instituto da Droga e da

Toxicodependência, Santa Maria da Feira, 25 November 2004.
Castro-Caldas, A. Presidência do seminário Stalevo. Reunião da Sociedade Portuguesa de

Neurologia, Espinho, 27 November 2004.
Castro-Caldas, A. A Língua Materna nos Primeiros Anos de Escolaridade: a Perspectiva das

Ciências Neurocognitivas. Conferência “A Língua Portuguesa: Presente e Futuro”, Fundação
Calouste Gulbenkian, Lisboa, 6-7 December 2004.
Guerreiro, M. Abordagem Neuropsicológica no DCL. Simpósio do defeito Cognitivo Ligeiro à

demência de Alzheimer. 11ªs Jornadas de Saúde Mental do Algarve, 2004.
Guerreiro, M. Avaliação clinica e psicométrica do idoso. Acção de formação sobre saúde no

idoso, Hospital de Júlio de Matos, 2004.
Martins, I.P. Cefaleias trigemino vasculares. Reunião da Sociedade Portuguesa de Cefaleias,

Porto Santo, May 2004.
Martins, I.P. Identidade e Memória. XI Simpósio Bioética e Identidades - Conferência Albert

Schweitzer, Faculdade de Medicina de Lisboa, 2004.
Martins, I.P. Aphasias in children: neuroanatomical correlations. II Corso di formazione

permanente: Developmental cognitive neurosciences. Language: normal and pathological
development. Palazzo dei Congressi, Salsomaggiore Terme, Italy, 2004.
Martins, I.P. O teste das faces famosas. CADIN, Cascais, 2004.
Castro-Caldas, A. O Presente e o Futuro da Neuroimagiologia. UCP, Lisboa, 29 May 2004.
Prizes
2º Prémio TECNIFAR Cefaleias 2003 - “Cinesiofobia” awarded to Isabel Pavão Martins, Raquel
Gil Gouveia, Susana Borges, Elsa Parreira.
Castro-Caldas, A. Participação no Mestrado de Neurociências da Faculdade de Medicina de

Lisboa.
Castro-Caldas, A. Participação no Mestrado em Aprendizagem e Desenvolvimento Psicológico

da Faculdade de Ciências da Educação da Universidade Católica do Porto.
Castro-Caldas, A. Participação no 1º Curso de Pós-Graduação em Educação e Ensino de Surdos

da Universidade Moderna.
Castro-Caldas, A. Participação na Pós-Graduação em Neuropsicologia e Reabilitação da Escola

Superior de Saúde do Alcoitão .
Castro-Caldas, A. Organização e participação nos Mestrados em Educação Médica, Enfermagem

e Ciências da Fala do Instituto de Ciências da Saúde da Universidade Católica Portuguesa.
Castro-Caldas, A. Presidência e Coordenação do Simpósio “Desafios em Neurologia – Genética”

organizado pela Glaxo-Smith-Kline
Guerreiro, M. Impacto das disfunções neuropsicológicas na intervenção em Fisioterapia. Centro

de Medicina de Reabilitação do Alcoitão – Departamento de Fisioterapia, 2004.
Guerreiro, M. Neuropsicologia da Memória. 11ªs Jornadas de Saúde Mental do Algarve, Oficina

de Formação, 2004.
Guerreiro, M. Curso Pós-graduação em Psico Gerontologia. Escola Superior de Saúde de

Alcoitão, 2004.
Martins, I.P. Viés e factores de confundimento. II Curso de Introdução à Metodologia de

Investigação. Gabinete De Apoio À Investigação Científica Tecnológica e Inovação (GAPIC) da
Faculdade de Medicina de Lisboa, 2004.
Thesis Completed
Master Thesis
Cláudia Silva (2004) “Aferição de uma escala à população infantil portuguesa na faixa etária dos
6 aos 10 anos”. Mestrado em Neurociências, Faculdade de Medicina da Universidade de Lisboa.
Supervisor: I.P. Martins
Goretty Ferreira (2004) “Aferição de um teste QI não verbal: C-TONI”. Mestrado em

Neurociências, Faculdade de Medicina da Universidade de Lisboa. Supervisor: I.P. Martins
Margarida Lobo Antunes (2004) “Estudo Neurocomportamental de Crianças e Adolescentes com

Traumatismos Craneo-encefálicos Fechados”. Mestrado em Neurociências, Faculdade de
Medicina da Universidade de Lisboa. Supervisor: I.P. Martins
Tiago Mendes (2004) “Evolução da Meta Memória e Avaliação da Memória Objectiva com a
Idade”. Mestrado em Neurociências, Faculdade de Medicina da Universidade de Lisboa.
Supervisor: I.P. Martins
Diploma Thesis
Ana Mécia Aleixo (2003/4) Nomeação de imagens de objectos em adultos idosos: a influência do
tipo de imagem, escolaridade e sexo. Licenciatura Bietápica em Terapia da Fala. Escola Superior
de Medicina e Reabilitação do Alcoitão. (Supervisor: Lauterbach M)
Ricardo Ávila (2003/4) Percepção visuespacial em individuos com deficit cognitivo. Licenciatura
em psicologia. Universidade de Lusófona de Humanidades. Não aprovado. Supervisor; M.
Guerreiro
Sara de Almeida Ferreira (2003/4) Fluência verbal no jovem adulto. Licenciatura Bietápica em
Terapia da Fala. Escola Superior de Medicina e Reabilitação do Alcoitão. Supervisor: L.
Albuquerque
Susana Isabel Martins Mestre (2003/4) Influência da escolaridade na capacidade de repetição em

afásicos com defeito de compreensão. Licenciatura Bietápica em Terapia da Fala. Escola Superior
de Medicina e Reabilitação do Alcoitão. Supervisor: G. Leal

Clinical Neuropharmacology Group
Carneiro, A.V., Costa, J., Borges, M. (2004) Statins for primary and secondary prevention of
coronary heart disease. A scientific review. Revista Portuguesa de Cardiologia 23(1):95-122.
Gouveia, M., Borges, M., Costa, J., Carneiro, A.V. (2004) Burden of disease from
hypercholesterolemia in Portugal. Revista Portuguesa de Cardiologia 23(2):255-70.
Gouveia, M., Borges, M., Costa, J., Oliveira, E., David, C., Carneiro, A.V. (2004) Costs of illness
due to hypeercholesterolemia in Portugal. Revista Portuguesa de Cardiologia 23(7-8):1037-54.
Coelho, M., Ferreira, J., Peralta, R., Biscoito, L., Albuquerque, L. (2004) Siderose superficial do
sistema nervoso central. Congresso de Neurologia 2004. Granja, 25-28 Novembro 2004. Sinapse,
Vol 4, Nº 2, pp 93.
Ferreira, J., Maia Silva, J., Freire, R., Pignatelli, J., Correia Guedes, L., Feijó, A., Rosa, M.M.,
Coelho, M., Costa, J., Noronha, A., Hewett, R., Marques Gomes, A., Cirne de Castro, J.L.,
Sampaio, C. (2004) Lesões cutâneas neoplásicas e pré-neoplásicas em doentes com doença de
Parkinson. Congresso de Neurologia 2004.
Books/Book Chapters
Ratilal, B.O., Costa, J., Sampaio, C. (2004) Anticonvulsants for preventing seizures in patients
with chronic subdural haematoma (Protocol for a Cochrane Review). In: The Cochrane Library,
Issue 3,. Chichester, UK: John Wiley & Sons, Ltd
Ratilal, B.O., Costa, J., Sampaio, C. (2004) Antibiotic prophylaxis for preventing meningitis in
patients with basilar skull fractures (Protocol for a Cochrane Review). In: The Cochrane Library,
Issue 3. Chichester, UK: John Wiley & Sons, Ltd.
Ratilal, B.O., Costa, J., Sampaio, C. (2004) Antibiotic prophylaxis for intracranial ventricular
shunts. (Title for a Cochrane Review). In: The Cochrane Library, Issue 4. Chichester, UK: John
Wiley & Sons, Ltd.
Costa, J., Ferreira, J.J., Borges, A., Espírito-Santo, C., Coelho, M., Sampaio, C. (2004) Botulinum
toxin type A therapy for cervical dystonia (Cochrane Review). In: The Cochrane Library, Issue 4.
Chichester, UK: John Wiley & Sons, Ltd.
Costa, J., Espírito-Santo, C., Borges, A., Ferreira, J.J., Coelho, M., Sampaio, C. (2004) Botulinum
Toxin Type A versus Anticholinergics for Cervical Dystonia (Cochrane Review). In: The
Cochrane Library, Issue 4. Chichester, UK: John Wiley & Sons, Ltd.
Costa, J., Borges, A., Espírito-Santo, C., Ferreira, J.J., Coelho, M., Sampaio, C. (2004) Botulinum
Toxin Type A versus Botulinum Toxin Type B for Cervical Dystonia (Cochrane Review). In: The
Cochrane Library, Issue 4. Chichester, UK: John Wiley & Sons, Ltd.
Costa, J., Espírito-Santo, C., Borges, A., Ferreira, J.J., Coelho, M., Sampaio, C. (2004) Botulinum
Toxin Type B for Cervical Dystonia (Cochrane Review). In: The Cochrane Library, Issue 4.
Chichester, UK: John Wiley & Sons, Ltd.
Rosa, M.M. (2004) Reacções adversas neuropsiquiátricas. In: Vasco A. Maria et al (Ed)
“Farmacovigilância em Portugal”, 303-322, INFARMED, 2004.
Sampaio, C. (2004) Avaliação da Relação Benefício-Risco. In: Vasco A. Maria et al (Ed),

“Farmacovilância em Portugal”, 427-440, INFARMED, 2004.
Sampaio, C. (2004) Unidade de Farmacovigilância Sul. In: Vasco A. Maria et al (Ed),

“Farmacovilância em Portugal”, 98-103, INFARMED, 2004.
Oswald, W. (coordenador), Caramona, M., Carneiro, C., Esteves, A.P., Filipe, H., Gonçalves, J.,
Macedo, T., Pinheiro, R.L., Rodrigues, A., Sampaio, C., Teixeira, A.A. (2004) Prontuário
Terapêutico, 5ª edição.
Almeida-Freire, R., Ferreira, J.J., Costa, J., Sampaio, C. Prevalence Studies in Parkinson’s
Disease: A Systematic Review of Prospective Data Sets. 8th International Congress of
Parkinson’s Disease and Movement Disorders, Rome, Italy, 14-17 June 2004 (Poster)
Correia-Guedes, L., Ferreira, J., Coelho, M., Rainha Campos, A., Almeida, A., Biscoito, L.,
Mendes Almeida, M. Bilateral brachial plexopathy as presenting symptom of B cell lymphoma.
14th Meeting of the European Neurological Society. Barcelona, 26-30 Junho 2004. J Neurol 2004,
Vol. 25, Suppl 3: P656.
Mendes Almeida, M. Bilateral brachial plexopathy as presenting symptom of B cell lymphoma.
14th Meeting of the European Neurological Society. Barcelona, 26-30 June 2004. (Poster)
David, C., E. Oliveira, A.G. Almeida, J. Costa, P. Marques, M.C. Vagueiro. Short-term effect of
air pollution on stroke hospital admissions. European Society of Cardiology Congress, Munich,
Germany, 28 August – 2 September 2004.
Sampaio, C. Neoplastic and preneoplastic skin lesions in Parkinson`s disease: a cross-sectional
clinical survey in PD patients and age-matched controls. 8th International Congress of
Parkinson`s Disease and Movement Disorders. Roma, 13-17 June 2004. Mov. Disord. 2004, Vol
19, Issue S9:P672.
Ferreira, J.J., J.M. Silva, R. Freire, ,Pignatelli, J., Guedes, L.C, Feijó, A. Neoplastic and
Paraneoplastic Skin Lesions in Parkinson’s Disease: A cross-sectional clinical survey in PD
patients and age-matched controls. 8th International Congress of Parkinson’s Disease and
Movement Disorders, Rome, Italy, 14-17 June 2004 (Poster)
Ferreira, J.. A therapeutic exploratory, single arm, multicentre trial to evaluate the efficacy and
safety of levetiracetam, up to 4000 mg/day, on levodopa induced dyskinesias in adults with
idiopathic parkinson's disease. European Federation of Neurological Societies, Paris, France, 4-7
September 2004. (Poster)
Ferreira, J., J. Maia Silva, R. Freire, J. Pignatelli, L. Correia Guedes, A. Feijó, M.M. Rosa, M.
Coelho, J. Costa, A. Noronha, R. Hewett, A. Marques Gomes, J.L. Cirne de Castro, C. Sampaio.
Neoplastic and preneoplastic skin in Parkinson’s disease patients. European Federation of
Neurological Societies, Paris, France, 4-7 September 2004. (Poster)
Giladi, N., on Behalf of the European LARGO Study Group. Rasagiline treatment can improve
freezing of gait in advanced Parkinson’s disease; a prospective randomized, double blind,
placebo and entacapone controlled study. 8th International Congress of Parkinson’s Disease and
Movement Disorder’s, Rome, 13-17 June 2004. (Poster)
Lees, A., Gershanik, O., Blin, O., Behari, M., Otero, E., Ferreira, J., Aguilar, M., Kies, B., Castro-
Caldas, A. Piribedil efficacy in monotherapy (150 to 300 mg/day) in de novo Parkinsonian
patients: a 6-month intermediate analysis of the 2-year Parkinson-Regain Study. American
Academy of Neurology 56th Annual Meeting. São Francisco, 24 April-1 May 2004. Neurology,
Vol 62, nº 7, suppl 5: A399.
patients: a 6-month intermediate analysis of the 2-year Parkinson-Regain Study. American
Academy of Neurology 56th Annual Meeting. São Francisco, 24 April-1 May 2004. (Poster)
patients: a 6-month intermediate analysis of the 2-year Parkinson-Regain Study. 8th International
Congress ps Parkinson’s Disease and Movement Disorders, Rome, June 13-17 2004 (Poster)
Rascol, O., Brooks, D.J., Melamed, E., Oertel, W., Poewe, W., Stocchi, F., Tolosa, E., on Behalf
of the Largo Study Group. A comparative randomised study of rasagiline versus placebo or
entacapone as adjunct to levodopa in Parkinson`s disease (PD) patients with motor fluctuations
(the Largo study). American Academy of Neurology 56th Annual Meeting. São Francisco, 24
April-1 May 2004. (Oral Communication)
Rascol, O., Brooks, D.J., Melamed, E., Oertel, W., Poewe, W., Stocchi, F., Tolosa, E, on Behalf
of the Largo Study Group. A comparative randomised study of rasagiline versus placebo or
entacapone as adjunct to levodopa in Parkinson`s disease (PD) patients with motor fluctuations
(the Largo study). American Academy of Neurology 56th Annual Meeting. São Francisco, 24
April-1 May 2004. Neurology, Vol 62, nº 7, suppl 5: A346.
Rascol, O., D.J. Brooks, E. Melamed, W. Oertel, W. Poewe, F. Stocchi, E. Tolosa. Effect of
rasagiline on tremor in levodopa-treated Parkinson's disease patients (LARGO Study). European
Federation of Neurological Societies, Paris, France, 4-7 September 2004. (Poster)
Stocchi, F., on Behalf of the LARGO Study Group. Effect of rasagiline on severity of OFF in
Parkinson’s Disease. 8th International Congress of Parkinson’s disease and Movement Disorders,
Rome, 13-17 June 2004. (Poster)
Barroso, C., João Costa, João de Sá, Nuno Cristino, Francisco Mascaranhas, José Pimentel.
Gliomatose cerebri: um tumor cerebral raro. Sinapse 2004, Vol 4, nº2:102.
Coelho, M., Ferreira, J., Peralta, R., Biscoito, L., Albuquerque, L. Siderose superficial do sistema
nervoso central. Congresso de Neurologia 2004, Granja, 25-28 November 2004. (Oral
Communication)
Mendes Almeida, M. Plexopatia braquial bilateral como apresentação clínica de linfoma de
células B. Fórum de Neurologia 2004, Luso, 20-23 May 2004. (Oral Communication)
Costa, J., Borges, M., Gouveia, M., David, C., Oliveira, E., Vaz-Carneiro. Epidemiologia da
Hipercolesterolémia e Carga da Doença Atribuível à Hipercolesterolémia. Realidade
Portuguesa. 18ª Reunião do Grupo de Estudos das Doenças Cerebrovasculares, Tomar, 3 April
2004. (Oral Communication)
Costa, J., Evangelista, T., de Carvalho, M. Parésia Unilateral do Diafragma na Miopatia das
Cinturas. Reunião da Primavera da Sociedade Portuguesa de Estudos de Doenças
Neuromusculares, Tomar, 8 May 2004. (Oral Communication)
Costa, J., Ferro, J.M., Matias-Guiu, J., Alvarez-Sabin, J., Torres, F. Meta-analysis of Triflusal
Studies. 23rd European Conference on Microcirculation, Lisboa, 8-11 September 2004. (Oral
Communication).
Costa, J., Nuno Cristino, Domingos Coiteiro, José Miguéns, João Lobo Antunes, José Pimentel.
Localizações Raras de Metástases no Neuro-eixo. Congresso Português de Neurologia de 2004,
Espinho, 25-27 November 2004. (Oral Communication)
Sampaio, C. Lesões cutâneas neoplásicas e pré-neoplásicas em doentes com doença de
Parkinson. Congresso de Neurologia 2004, Granja, 25-28 November 2004. (Oral
Communication)
Ferreira, J.J., João Maia Silva, Rita Freire, João Pignatelli, Leonor Guedes, Alexandra Feijó,
Mário Miguel Rosa, Miguel Coelho, João Costa, Ana Noronha, Sara Freitas, Russell Hewett, A.
Marques Gomes, J.L. Cirne de Castro, Cristina Sampaio. Lesões Cutâneas Neoplásicas e Pré-
neoplásicas em Doentes com Doença de Parkinson. Sinapse 2004, Vol 4, nº2:134.
Parracho da Costa, J., Mamede de Carvalho. Utilização terapêutica das imunoglobulinas

intravenosas (IGIV) em doenças neuromusculares. Revisão sistematizada da literatura. Fórum de
Neurologia 2004, Luso, 20-23 May 2004. (Oral Communication)
Parracho da Costa, J., Mamede de Carvalho. Lesão severa do nervo frénico na polineuropatia
inflamatória desmielinizante crónica (PIDC), com resposta à terapêutica. Fórum de Neurologia
2004, Luso, 20-23 May 2004. (Oral Communication)
Parracho da Costa, J., Joana Ruivo, Nuno Cristino, Graça Sá, José Miguéns, João Lobo Antunes,
José Pimentel. Ganglioglioma do cone medular. Fórum de Neurologia 2004, Luso, 20-23 May
2004. (Oral Communication)
Rainha Campos, C., Faria, J., Costa, A., Macedo, D., Coiteiro, J.P. Farias. Avaliação da
Hemorragia Intraventricular e da idade como factores preditores de Vasospasmo Arterial e do
prognóstico na HSA por rotura de aneurisma. XVIII Reunião da SPNC (Sociedade Portuguesa
de Neurocirurgia), Cascais, 21-23 November 2004.
Rosa, M.M., Ferreira, J.J. Coelho, M.S., Gilles de la Tourette. Manifestações oculares. Fórum de
Neurologia da Sociedade Portuguesa de Neurologia, Luso, 20 May 2004.
Rosa, M.M. Efficacy and Safety of Pharmacological Interventions in Parkinson’s Disease

Dementia and Dementia with Lewy Bodies. Reunião da Secção de Doenças do Movimento,
Tomar, 29 October 2004.
Coelho, M., Ferreira, J.J., Dias, B., Sampaio, C., Pavão Martins, I., Castro-Caldas, A. Time
perception: effect of aging and parkinsonism. 5º Simpósio da Fundação Bial: Aquém e Além do
Cérebro, Porto, 31 March-3 April 2004.
Ferreira, J. Clues for the Diagnosis of Parkinson’s. EPDA Conference, Lisbon, 6-9 May 2004.
Ferreira, J. Critical Appraisal of Clinical Trials. European Society for Clinical

Neuropharmacology , 7° Congress, Trieste, 5-9 May 2004.
Ferreira, J. Revisão Sistemática do Tratamento das Alterações do Sono na Doença de Parkinson.

Congresso Brasileiro de Neurologia, XXI edição, Brasília/DF, 9 and 14 October 2004.
Rosa, M.M. Avaliação e diagnóstico da Doença de Parkinson - Projecto movimento. Peniche, 18

February 2004.
Rosa, MM. Reacções adversas em Neurologia. Curso de avaliação periódica de segurança de

medicamentos, 31 March – 14 June 2004.
Rosa, MM. Avaliação e diagnóstico da Doença de Parkinson - Projecto movimento. Évora, 26

March 2004.
Rosa, MM. Operacionalidade dos ensaios clínicos. Institute for International Research, Lisbon,
23 April 2004.
Rosa, MM. Avaliação farmacoterapêutica: Valor terapêutico acrescentado. Utilização racional

do medicamento. Lisbon, 15 September 2004.
Rosa, M.M. Valor terapêutico acrescentado – papel do avaliador médico. Faro, 3 November
2004.
Rosa, M.M. Farmacologia Clínica. Aula de Mestrado IMM, Lisboa, 11 November 2004.
Sampaio, C. Overview of PD treatments and concept of evidence-based medicine. MDS course

Management of Parkinson’s Disease: An Evidence-Based Review. Miami, USA, January 2004
Sampaio, C. Amantadine and anticholinergic agents. MDS course Management of Parkinson’s

Disease: An Evidence-Based Review. Miami, USA, January 2004
Sampaio, C. Dopamine agonists. MDS course Management of Parkinson’s Disease: An

Evidence-Based Review. Miami, USA, January 2004
Sampaio, C. Breakout Sessions: Interactive Video Case Management Discussions(1) Initiating

treatment in PD. MDS course Management of Parkinson’s Disease: An Evidence-Based Review.
Miami, USA, January 2004.
Sampaio, C. Curso Pós-graduado de Actualização em Epilepsia. Faculdade de Medicina de

Lisboa, January 2004.
Sampaio, C. Guidance on the clinical development of medicinal products for neuropathic pain.
16th DIA annual Euromeeting, Prague, March 2004.
Sampaio, C. European Guidance for CNS drug development. IIR CNS Conference, Amsterdam,
March 2004.
Sampaio, C. Pharmacogenetics. GSK symposium, Lisbon, March 2004.
Sampaio, C. Iatrogenia medicamentosa e Farmacovigilância. Centro de Saúde. Setúbal, April

2004.
Sampaio, C. Clinical Trials Bottlenecks. Teaching Course on clinical trials. 7th ESCNP Congress,
Trieste, May 2004.
Sampaio, C. Levodopa in the treatment of Parkinson Disease. EPDA conference, Lisbon, May
2004.
Sampaio, C. COMT inhibitors in the treatment of Parkinson Disease. EPDA conference, Lisbon,
May 2004.
Sampaio, C. DIA meeting. Paris, May 2004.
Sampaio, C. Neuropathic pain: Clinical development of novel medicinal products. Madrid, May
2004.
Sampaio, C. Amostragem. Curso de Introdução a investigação cientifica. FML, May 2004.
Sampaio C. Variáveis. Curso de Introdução a investigação cientifica. FML, May 2004

Sampaio C. O investigador clínico e as GCP. Curso de Ensaios Clínicos. Novonordisk, Óbidos.

2004.
Sampaio, C. Simposium: Trivastal 50mg LP – Movement Disorders. Rome, Italy, June 12 2004.
Sampaio, C. Actual issues on EBNeurology. EFNS Congress, Paris September 2004.
Sampaio, C. Overview of PD treatments and concept of evidence-based medicine. MDS course

Management of Parkinson’s Disease: An Evidence-Based Review. Vienna, September 2004
Sampaio, C. Amantadine and anticholinergic agents. MDS course Management of Parkinson’s

Disease: An Evidence-Based Review. Vienna, September 2004
Sampaio, C. Breakout Sessions: Interactive Video Case Management Discussions(1) Initiating

treatment in PD. MDS course Management of Parkinson’s Disease: An Evidence-Based Review.
Vienna, September 2004.
Sampaio, C. Medicina Baseada na Evidência: Tratamento da Doença de Parkinson. Congresso

da Academia Brasileira de Neurologia. Brasília, October 2004.
Sampaio, C. Projecto Movimento: Curso sobre Doença de Parkinson (Sociedade Portuguesa de

Neurologia, Secção Doenças do Movimento). Centro de Saúde de Odivelas, Lisboa, 22 October
2004.
Sampaio, C. Projecto Movimento: Curso sobre Doença de Parkinson (Sociedade Portuguesa de

Neurologia, Secção Doenças do Movimento). Centro de Saúde de Sete Rios, Lisboa, 3 November
2004.
Sampaio, C. Surrogate end-points in the development of CNS products. Symposiun "Surrogate

Endpoints in the Early Clinical Development of CNS Drugs". Chicago, USA, November 2004.
Sampaio C. Módulo – Ensaios Clínicos. Curso de Farmacoepidemiologia. FML. November 2004.
Sampaio, C. Seminário Farmacovigilância. Curso de Farmacoepidemiologia. FML. November

2004.
Sampaio, C. Neurogenética: Curso de Formação Pós-Graduada. Sociedade Portuguesa de

Neurologia, Espinho, 27-28 November 2004.
Sampaio, C. Exploração Funcional na Vertigem. Curso Pós-graduado Teórico-Prático. Lisboa,

10-11 December 2004.
Prizes
Prémio de Neurologia Corino de Andrade / NOVARTIS, 2004.

Responsável pelo Módulo de Neurologia no Curso de Terapia da Fala da Escola Superior de

Saúde do Alcoitão (Directora do curso: Profª. Dr.ª Emília Santos); 2001-
Responsável pela aula de Neuro-anatomia do Módulo de Neuropsicologia no Curso de Terapia da

Fala da Escola Superior de Saúde do Alcoitão (Directora do curso: Profª. Dr.ª Emília Santos);
2004-
Oncology Programme
Nutrition and Metabolism Unit
Machado, M.V., Gonçalves, M.S., Cortez-Pinto, H. (2004) Metabolismo do ferro em alcoólicos

crónicos e durante a abstinência”. Jornal Português de Gastrenterologia (Supl.) 11:186-190.
Santos, M., Francisco Mascarenhas, I. Monteiro Grillo, Álvaro Almeida, José Robalo Soares,
Luís Metzner Serra, A. Castanheira Dinis (2004) Radioterapia Extereotáxica Conformacional no
Hemangioma Orbitário. Caso Clínico. Oftalmologia; Revista da Sociedade Portuguesa de
Oftalmologia 4:21-27
Books/Book Chapters
Camilo, M.E. (2004) Terapêutica nutricional nas doenças hepáticas. In: Terapêutica em
Hepatologia, Biblioteca Hepatológica. Editor – F. Carneiro Chaves, Porto, pp 7-11.
Sobotka, L., Camilo, M.E. (2004) Metabolic complications of parenteral nutrition. In: Basics In
Clinical Nutrition. Editors – L. Sobotka, S. P. Allison, P. Fürst, R. Meier, M. Pertkiewicz, P.
Soeters, 3rd Edition, Galén-Prague, pp 275-280.
Jonkers, C.F., Camilo, M.E. (2004) Nutrition therapy for neurological disorders. In: Basics In
Clinical Nutrition. Editors – L. Sobotka, S. P. Allison, P. Fürst, R. Meier, M. Pertkiewicz, P.
Soeters, 3rd Edition, , Galén-Prague, pp 416-422.
Lourenço, R., Camilo, M.E. (2004) Parenteral Nutrition. In: Business Briefing: Long-term
Healthcare. Advisory Panels, London, pp 2-5.
Banza, A., Horta, L., Marques-Vidal, P., Lavinha, I. "Avaliação nutricional de atletas de alta
competição de várias modalidades". In: II Simpósio Internacional de Nutrição, Actividade Física
e Saúde, Lisbon, Portugal, November 2004. Universidade Lusófona de Humanidades e
Tecnologias, 2004.
Banza, A, Horta, L., Marques-Vidal, P., Lavinha, I. "Avaliação dos conhecimentos e hábitos
alimentares de atletas de competição e alta competição de várias modalidades". In: II Simpósio
Internacional de Nutrição, Actividade Física e Saúde, Lisbon, Portugal, November 2004.
Universidade Lusófona de Humanidades e Tecnologias. 2004.
Cardoso, J.M., Cravo, M., Marques Vidal, P., Camilo, M.E. Are overweight hospitalised elderly
patients at risk of malnutrition? 26th Congress of the European Society for Clinical Nutrition and
Metabolism (ESPEN), Lisbon, Portugal, September 2004. Clinical Nutrition 2004; 23: 792.
Cortez-Pinto, H., Martins, A., Machado, M., Gonçalves, M., Steffensen, S., Carvalho, T., Silva,
M.C., Marques-Vidal, P., Moura, M.C. “Absence of association between promoter
polymorphism of tumor necrosis factor, valine-alanine manganese superoxide dismutase,
interleukin 10 or cd14 endotoxin receptor gene and susceptibility to alcoholic liver disease”.
Postgraduate course & 55th Annual Meeting of the American Association for the Study of Liver
Diseases (AASLD). Boston - USA, November, 1-4, 2004 (Poster)
Gaspar. A, Sousa. L-, Brito. M-, Marques-Vidal. P. "Factors related to refusal of food by
hospitalized patients". In: 26th Congress of the European Society of Parenteral and Enteral
Nutrition (ESPEN), Lisbon, Portugal, September 2004. Clinical Nutrition 2004; 23: 909.
Germano, S., M. Santos, T Almeida, I. Monteiro Grillo. CT image fusion to evaluate prostate
gland motion and volume change between planning CT and repeat CT after four weeks of
external radiotherapy treatment. (Poster) 23rd Annual ESTRO Meeting Amsterdam, October
2004.Radiotherapy Oncology 2004;73(suppl 1) S399.
Ibrahim, R., Ferrières, J., Marques-Vidal, P. ‘’Relations entre marqueurs de l'obésité et facteurs
de risque cardiovasculaire chez des sujets d'âge moyen’’. In: XIVèmes Journées Européennes de
la Société Française de Cardiologie 2004 ; Paris, France, 21-24 January 2004.
Lemos, M.J., M. Ortiz Monterrey, O. Condon, I. Monteiro Grillo. Results of cervical carcinoma
treated with external radiotherapy and high dose rate brachytherapy (poster) Joint
Brachytherapy Meeting GEC/ESTRO-GLAC-ABS, Barcelona, May 2004. Radiotherapy and
Oncology 2004; 71 (Suppl.2.): S76.
Lemos, M.J., M. Ortiz Monterrey, M.M. Sanchez Aragon, I. Monteiro Grillo. Adjuvant high dose
rate brachytherapy alone or combined with external beam radiation in endometrial cancer
(poster) Joint Brachytherapy Meeting GEC/ESTRO-GLAC-ABS, Barcelona, May 2004.
Radiotherapy and Oncology 2004; 71 (Suppl.2.): S133-S134.
Marques Vidal, P., Ravasco, P., Camilo, M.E. Nutrients and colorectal cancer: a meta-analysis.
26th Congress of the European Society for Clinical Nutrition and Metabolism (ESPEN), Lisbon,
Portugal, September 2004. Clinical Nutrition 2004; 23: 912.
Marques Vidal, P., Ravasco, P., Camilo, M.E. Foodstuffs and colorectal cancer: a meta-
analysis. 26th Congress of the European Society for Clinical Nutrition and Metabolism (ESPEN),
Lisbon, Portugal, September 2004. Clinical Nutrition 2004; 23: 912–913.
Marques-Vidal, P., Dias, C.M. “Trends in the prevalence of overweight and obesity in Portugal,
1995-1999”. In: European Congress of Epidemiology; Porto, Portugal, September 2004. Journal
of Epidemiology and Community Health 2004; p. A37.
Marques-Vidal, P., Dias, C.M. “Trends in the prevalence of diagnosed hypertension in Portugal”.
In: European Congress of Epidemiology; Porto, Portugal, September 2004. Journal of
Epidemiology and Community Health 2004; p. A38.
Marques-Vidal, P., Dias, C.M. "Prevalence and determinants of obesity in Portugal: the National
Health Survey 1998-9". In: Meeting of the Working Group on Epidemiology and Prevention of
the European Society of Cardiology, Elsinore, Denmark, June, 2004.
Marques-Vidal, P., Dias, C.M. "Prevalence of reported hypertension in Portugal: the National
Health Survey 1998-9". In: Meeting of the Working Group on Epidemiology and Prevention of
the European Society of Cardiology, Elsinore, Denmark, June 2004.
Marques-Vidal, P., Dias, C.M. "Trends in smoking prevalence in Portugal". In: Meeting of the
Working Group on Epidemiology and Prevention of the European Society of Cardiology,
Elsinore, Denmark, June 2004.
Marques-Vidal, P., Dias, C.M. "Trends in the prevalence of diagnosed hypertension in Portugal".
In: Meeting of the Working Group on Epidemiology and Prevention of the European Society of
Cardiology, Elsinore, Denmark June 2004.
Marques-Vidal, P., Dias, C.M. "Trends in the prevalence of diagnosed diabetes in Portugal". In:
Meeting of the Working Group on Epidemiology and Prevention of the European Society of
Cardiology, Elsinore, Denmark, June 2004.
Marques-Vidal P., Dias, C.M. "Trends in the prevalence of overweight and obesity in Portugal,
1995-1999". In: Meeting of the Working Group on Epidemiology and Prevention of the European
Society of Cardiology, Elsinore, Denmark, June 2004.
Marques-Vidal, P., Dias, C.M. "Prevalence of reported hypertension in Portugal: the National
Health Survey 1998-1999". In: European Congress of Epidemiology, Porto, Portugal, September
2004. Journal of Epidemiology and Community Health 2004; p. A98.
Marques-Vidal, P. "Medicine usage and handling in a sample of Portuguese students". In:

European Congress of Epidemiology, Porto, Portugal, Deptember 2004. Journal of Epidemiology
and Community Health 2004; p. A97.
Marques-Vidal, P., Dias, C.M. "Trends in smoking prevalence in Portugal". In: European
Congress of Epidemiology, Porto, Portugal, September 2004. Journal of Epidemiology and
Community Health 2004; p. A98.
Marques-Vidal, P., Dias, C.M. "Trends in the prevalence of diagnosed diabetes in Portugal". In:
European Congress of Epidemiology, Porto, Portugal, September 2004. Journal of Epidemiology
and Community Health 2004; p. A98.
Marques-Vidal, P., Dias, C.M. "Trends and determinants of alcohol consumption in Portugal:
results from the National Health Surveys 1995-1996 and 1998-1999". In: European Congress of
Epidemiology, Porto, Portugal, September 2004. Journal of Epidemiology and Community
Health 2004; p. A98.
Marques-Vidal, P., Milagre, V. "Oral health behaviours and determinants in a sample of

Portuguese students". In: European Congress of Epidemiology, Porto, Portugal, September 2004.
Journal of Epidemiology and Community Health 2004; p. A98.
Marques-Vidal, P., Dias, C.M. "Calcium intake (as assessed by dairy products intake) is related
to body mass index in men but not in women". In: 26th Congress of the European Society of
Parenteral and Enteral Nutrition (ESPEN), Lisbon, Portugal, September 2004. Clinical Nutrition
2004; 23: 822-823.
Matos, F, Soeiro, L., Marques-Vidal, P. “Are there any relationships between spirometry data
and fitness in elderly subjects?”. In: Meeting of the Working Group on Epidemiology and
Prevention of the European Society of Cardiology 2004; Elsinore, Denmark, 9-12 June 2004.
Messias, A., Eusébio, R., Nunes, N., Marques-Vidal, P., Lobato, C. "Nutritional risk screening in
a Portuguese community hospital". In: 26th Congress of the European Society of Parenteral and
Enteral Nutrition (ESPEN), Lisbon, Portugal, September 2004. Clinical Nutrition 2004; 23: 778-
2779.
Monterrey, M.O., M.M. Sanchez Aragon, M. Lemos, I. Monteiro Grillo. Adjuvant intravaginal
high dose rate brachytherapy in endometrial adenocarcinoma. Joint Brachytherapy Meeting
GEC/ESTRO-GLAC-ABS, Barcelona, May 2004. Radiotherapy and Oncology 2004; 71
(Suppl.2.): S136-S137.
Pina, M.F., Almeida, T.M., Monteiro Grillo, I., Marques-Vidal, P. Conservative treatment of anal
canal carcinoma: retrospective study. (poster) In: 23rd Annual Meeting of the European Society
for Therapeutical Radiology and Oncology (ESTRO), Amsterdam, Netherlands, October 2004.
Ramalho, R., Cortez-Pinto, H., Solá, S., Castro, R., Camilo, M.E., Moura, M.C., Rodrigues, C.
Enhanced apoptosis and bcl-2 protein production in the liver of patients with steatohepatitis. 39th
Meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany, 14-18
April 2004; J. Hepatology.
Ravasco, P., Monteiro Grillo, I., Pinto, R., Marques Vidal, P., Camilo, M. New insights on the
etiopathogenesis of nutritional deterioration in colorectal cancer. 26th Congress of the European
Society for Clinical Nutrition and Metabolism (ESPEN), Lisbon, Portugal, September 2004.
Clinical Nutrition 2004; 23: 875.
Ravasco, P., Monteiro Grillo, I., Pinto, R., Camilo, M. Colorectal cancer: cytokines and
nutritional deterioration during radiotherapy. 26th Congress of the European Society for Clinical
Nutrition and Metabolism (ESPEN), Lisbon, Portugal, September 2004. Clinical Nutrition 2004;
23: 876.
Ravasco, P., Monteiro Grilllo, I., Pinto, R., Marques Vidal, P., Camilo, M. New insights on the
etiopathogenesis of nutritional deterioration in colorectal cancer. 23 rd Annual Meeting of the
European Society for Therapeutical Radiology and Oncology (ESTRO), Amsterdam, The
Netherlands, October 2004. Radiotherapy & Oncology 2004; 73 (suppl 1): S262.
Ravasco, P., Camilo, M., Monteiro Grillo, I., Pinto, R. Nutritional deterioration in colorectal
cancer: new insights in the pathogenesis. 40th American Society of Clinical Oncology (ASCO)
Annual Meeting 2004, New Orleans, United States of America, June 2004. Journal of Clinical
Oncology 2004, ASCO Annual Meeting Proceedings (Post-Meeting Edition); vol. 22, Nº 14S
(July 15 supplement) 2004: 3682.
Ravasco, P., I. Monteiro Grillo, Maria Camilo. Nutritional deterioration in colorectal cancer:
new insights in the pathogenesis. The Faseb Journal 2004; 18 (no.4): A148.
Ravasco, P., Monteiro Grillo, I., Pinto, R., Camilo, M. Colorectal cancer: cytokines and
nutritional deterioration during radiotherapy. 90th Scientific Assembly and Annual Meeting of
the Radiological Society of North America (RSNA) – RSNA 2004 (Radiology’s Global Forum),
Chicago, Illininois, United States of America, November 2004. Radiology 2004; 23 (4): 876.
Ravasco, P., Monteiro Grillo, I., Camilo, M. Are energy expenditure and nutritional variables
determined by cancer’ intrinsic characteristics? FASEB’s (Federation of the American Societies
of Experimental Biology) Experimental Biology 2004: “Translating the Genome”, Washington
DC, United States of America, April 2004. The FASEB Journal 2004; 18 (4): A148.
Ravasco, P., Monteiro Grillo, I., Camilo, M. Nutritional deterioration in colorectal cancer: new
insights in the pathogenesis. FASEB’s (Federation of the American Societies of Experimental
Biology) Experimental Biology 2004: “Translating the Genome”, Washington DC, United States
of America, April 2004. The FASEB Journal 2004; 18 (4): A148.
Ruivo, A., Marques Vidal, P., Camilo, M.E. Can we believe in reported height and weight? 26th
Congress of the European Society for Clinical Nutrition and Metabolism (ESPEN), Lisbon,
Portugal, September 2004. Clinical Nutrition 2004; 23:768-769.
Santos, M., F. Pina, M. Ortiz, P. Marques Vidal,. I. Monteiro Grillo. Adjuvant Chemotherapy and
radiotherapy association in the carcinoma gastric operable: evaluation of the results. Radiotherapy
Oncology 2004;73(suppl 1) S273.
Sousa Guerreiro, C., Brito, M., Marques-Vidal, P., Cravo, M., Nobre Leitão, C. “Polymorphism
of APC gene at codon 1882 modifies susceptibility for colorectal cancer (CRC) according to fat
and calcium intake”. In: 26th Congress of the European Society of Parenteral and Enteral
Nutrition (ESPEN), Lisbon, Portugal, September 2004. Clinical Nutrition 2004; 24: 882.
Sousa, L., Gaspar, A., Brito, M., Marques-Vidal, P. "Over or undernourished? Nutritional status
of hospitalized patients". In: 26th Congress of the European Society of Parenteral and Enteral
Nutrition (ESPEN), Lisbon, Portugal, September 2004. Clinical Nutrition 2004; 23: 909-910.
Sousa, L., Gaspar, A., Brito, M., Marques-Vidal, P. "Food wastage in hospital: quantification
and related factors". In: 26th Congress of the European Society of Parenteral and Enteral
Nutrition (ESPEN), Lisbon, Portugal. Clinical Nutrition 2004; 23: 914-915.
Velho, S., Baptista, F., Marques Vidal, P. “Adequacy of dietary intake in elderly people with
regular leisure-time physical activity”. In: 4th European Congress on Nutrition and Health in the
Elderly. Toulouse, France, November 2004.
Velho, S, Baptista, F, Marques-Vidal, P. "Adequacy of dietary intake of elderly people with

regular leisure-time physical activity". In: 26th Congress of the European Society of Parenteral
and Enteral Nutrition (ESPEN), Lisboa, Portugal, September 2004. Clinical Nutrition 2004.
Alves, A.B., Carvalho, D., Gorayeb, M., Marques-Vidal, P., Monteiro Grillo, I. "Prevalência da
disfunção eréctil no cancro da próstata". In: Simpósio de Sexualidade e Saúde Sexual, Monte de
Caparica, Portugal, November 2004.
Condon, O., Marília Jorge, Maximino Ortiz, Isabel Monteiro Grillo, Pedro Marques Vidal.
Cirurgia conservadora e radioterapia no carcinoma in-situ da mama: resultados e factores
prognóstico de recidiva. 1º Congresso Nacional da Sociedade Portuguesa de Radioterapia
Oncologia, Cascais, May 2004.
Germano, S., I. Monteiro Grillo, F. Mascarenhas, M. Santos. Paragangliomas jugulo-carotídeos:

tratamento com radiocirurgia estereotáxica. 1º Congresso Nacional da Sociedade Portuguesa de
Radioterapia Oncologia, Cascais, May 2004.
Gorayeb, M., Marília Jorge, Filomena Pina, I. Monteiro Grillo. Análise retrospectiva do uso da
eritropoietina em doentes do Serviço de Radioterapia do Hospital de Santa Maria.1º Congresso
Nacional da Sociedade Portuguesa de Radioterapia Oncologia, Cascais, May 2004.
Jorge, M., M. Ortiz, O. Abad, I. Monteiro Grillo. Sarcoma uterino em doentes com tumores da
mama medicadas com tamoxifeno (Poster) lº Congresso Nacional da Sociedade Portuguesa de
Radioterapia Oncologia, Cascais, May 2004.
Jorge, M., M. Ortiz, O. Abad, I. Monteiro Grillo. Braquiterapia intravaginal adjuvante com alta
taxa de dose no adenocarcinoma do endométrio (Poster) lº Congresso Nacional da Sociedade
Portuguesa de Radioterapia Oncologia, Cascais, May 2004.
Marques, F.O., M. Jorge, M. Ortiz, I. Monteiro Grillo, C.P. Miguel, C. Marques. A tomografia
computorizada no planeamento da braquiterapia intracavitária. 1º Congresso Nacional da
Sociedade Portuguesa de Radioterapia Oncologia, Cascais, May 2004.
Martins, A., Cortez-Pinto, H., Marinho, R., Fatela, N., Ramalho, F., Moura, M.C. “Prevalência
de infecções fúngicas e bacterianas em doentes internados com cirrose hepática”. XXIV
Congresso Nacional de Gastrenterologia, Figueira da Foz, 2-5 June 2004.
Martins, A., Cortez-Pinto, H., Marinho, R., Fatela, N., Ramalho, F., Moura, M.C. “Hepatite
aguda alcoólica e pentoxifilina - experência de 2 anos numa Unidade de Hepatologia”. XXIV
Congresso Nacional de Gastrenterologia, Figueira da Foz, 2-5 June 2004.
Martins, A., Cortez-Pinto, H., Marinho, R., Fatela, N., Ramalho, F., Moura, M.C.
“Pseudomixoma peritonei”. A propósito de um caso clínico. XXIV Congresso Nacional de
Gastrenterologia, Figueira da Foz, 2-5 June 2004.
Matos Almeida, T., Filomena Pina, I. Monteiro Grillo, Pedro Marques Vidal. Tratamento
conservador do carcinoma do canal anal: estudo rectrospectivo. 1º Congresso Nacional da
Monteiro Grillo, I., Marília Jorge, Maximino Ortiz, Pedro Marques Vidal Resultados a longo
termo do tratamento conservador no carcinoma invasivo da mama 1º Congresso Nacional da
Medialdea, J.C., Francisco Mascarenhas, Filomena Pina, I. Monteiro Grillo. Sobrevivência a

longo prazo em doentes com adenocarcinoma do pulmão em estadios localmente avançados. 1º
Congresso Nacional da Sociedade Portuguesa de Radioterapia Oncologia, Cascais, May 2004.
Ramalho, R.M., Cortez-Pinto, H., Castro, R.E., Solá, S., Moura, M.C., Camilo, M.E., Rodrigues,
C.M.P. Aumento de apoptose e Bcl-2 no fígado de doentes com esteatohepatite alcoólica (NASH).
In: XXIV Congresso Nacional de Gastrenterologia e Endoscopia Digestiva, Figueira da Foz,

Portugal, 2-5 June 2004. Jornal Português de Gastrenterologia 2004, 11 (3): 41.
Ravasco, P., Monteiro Grillo, I., Pinto R., Marques-Vidal, P., Camilo, E. Novos conhecimentos
na etiopatogénese da deterioração nutricional no cancro colorectal. In: XXIV Congresso
nacional de gastrenterologia e endoscopia digestiva; Figueira da Foz, Portugal, 2-5 June 2004.
Jornal Português de Gastrenterologia 2004, 11 (3):1.
Ravasco, P., Monteiro Grillo, I., Pinto, R., Camilo, M.E. Cancro Colorectal: citocinas e
deterioração nutricional durante a Radioterapia. In: XXIV Congresso Nacional de
Gastrenterologia e Endoscopia Digestiva, Figueira da Foz, Portugal, 2-5 June 2004. Jornal
Português de Gastrenterologia 2004, 11 (3):2.
Ravasco, P., Monteiro Grillo, I., Pinto, R., Camilo, M.E. Cancro Colorectal: citocinas e
deterioração nutricional durante a Radioterapia. 1º Congresso Nacional da Sociedade
Portuguesa de Radioterapia e Oncologia, Cascais, Portugal, 20-22 May 2004. Livro de Resumos
(Abstract Book). Awarded the Prize for the best original work presented in the Congress.
Santos, M, F. Mascarenhas, Sofia Faustino, Sara Germano, I. Monteiro Grillo, Álvaro Almeida,
David Coutinho, José Robalo Radioterapia estereotáxica fraccionada no hemangioma cavernoso
da órbita 1ºCongresso Nacional da Sociedade Portuguesa de Radioterapia Oncologia, Cascais,
May 2004.
Santos, M., Filomena Pina, Maximino Ortiz, I. Monteiro Grillo. Associação de químio e
radioterapia adjuvante no carcinoma gástrico operável: avaliação dos resultados. 1º Congresso
Nacional da Sociedade Portuguesa de Radioterapia Oncologia, Cascais, May 2004.
Sobral Dias, M., Cortez-Pinto, H., Fatela, N., Ramalho, F., Moura, M.C. “Síndrome febril num
doente cirrótico”. Caso clínico. XXIV Congresso Nacional de Gastrenterologia, Figueira da Foz,
2-5 June 2004.
Sobral Dias, M., Cortez-Pinto, H., Velosa, J., Moura, M.C. “Doença de Wilson: forma de
apresentação e evolução clínica”. Caso clínico. XXIV Congresso Nacional de Gastrenterologia,
Figueira da Foz, 2-5 June 2004 .
Other Publications
Ravasco, P., Camilo, M.E. (2004) Necessidades nutricionais da criança dos 1 aos 3 anos. 29º
Boletim da Associação Portuguesa de Nutrição Entérica e Parentérica (APNEP) Junho 2004: 15-
19.
Camilo, M.E. (2004) Dysphagia on the Council of Europe’s agenda. Syllabus of the Satellite
Symposium: Dysphagia, food and nutrition: from clinical evidence to dietary adaptation. 26th
Portugal, 11-14 September 2004.
Cristina, I. (2004) Necessidades nutricionais normais em pediatria - resumo das linhas

orientadores da ASPEN 2002. 29º Boletim da Associação Portuguesa de Nutrição Entérica e
Parentérica (APNEP), Junho 2004: 8-15.
Camilo, M.E. Moderator of the round table: “Insulin Resistance” in the Monothematic
Conference: “Non-alcoholic steatohepatitis: from cell biology to clinical practice” promoted by
the European Association for the Study of the Liver, Estoril, Portugal, 17-18 September 2004.
Camilo, M.E. Moderator of the Opening session/key note address of the 26th Congress of the
European Society for Clinical Nutrition and Metabolism (ESPEN), Lisbon, Portugal, 11-14
September 2004.
Camilo, M.E. Moderator of the NOVARTIS Satellite Symposium: “Dysphagia, food and
nutrition: from clinical evidence to dietary adaptation” and lecture: “Dysphagia on the council
of Europe’s agenda”. 26th Congress of the European Society for Clinical Nutrition and
Metabolism (ESPEN), Lisbon, Portugal, 11-14 September 2004.
Camilo, M.E. Moderator and discussant of the Symposium on Parenteral Nutrition

“Structokabiven” organized by Fresenius-Kabi. Porto Santo, Portugal, March 2004.
Cortez-Pinto, H. Moderator of the session: “Fígado. Curso Pós-Graduado para Clínicos e

Medicina Geral e Familiar”. Póvoa de Varzim, Portugal, 16 January 2004.
Cortez-Pinto, H. Chronic hepatitis C. The impact of steatosis and alcohol. Invited Lecture at the
II International Symposium on Viral Hepatitis of Lisbon. Lisbon, Portugal, 5-6 March 2004.
Cortez-Pinto, H. Moderator of oral communications: “Metabolic and drug-induced liver

disease”, 39th Meeting of the European Association for the Study of the Liver (EASL), Berlin,
Germany, 14-18 April 2004.
Cortez-Pinto, H. PEG: Reflexões. Invited lecture in the Session: PEG at the 3º Curso de
Endoscopia Digestiva, organized by SPED, Lisbon, Portugal, 22 April 2004.
Cortez-Pinto, H. Alterações digestivas. No Painel: “O doente obeso e as Co-Morbilidades.

Invited lecture at the V Jornadas de Pneumologia em Medicina Familiar, Lisbon, Portugal, 6
May 2004.
Cortez-Pinto, H. Alcoholic liver disease and NASH: clínico-pathological correlates. Invited
lecture at the Session: “Alcohol and the liver: from molecular biology to clinics”, in ESBRA
Nordman Award Meeting 2004 – Alcohol and Cannabis, organizado pela European Society of
Biochemical Research on Alcoholism (ESBRA), Lisbon, Portugal, 28-29 May 2004.
Cortez-Pinto, H. Moderator of the Sessão de Comunicações Livres. Congresso Nacional de

Gastrenterologia, Figueira da Foz, Portugal, 3-5 June 2004.
Cortez-Pinto, H. The role of liver biopsy in alcoholic and non-alcoholic fatty liver diseases”.
Invited lecture at the EASL Monothematic Single Topic Conference: “The role of liver biopsy in
the diagnosis and management of chronic liver disease”, EASL; Turim, Italy, 14-15 June 2004.
Cortez-Pinto, H. História natural da Esteatohepatite não alcoólica”. In the Session:

“Esteatohepatite não alcoólica”. Invited Lecture at the II Reunião Ibérica de Hepatologia,
Marbella, Spain, 2-3 July 2004.
Cortez-Pinto, H. Pathophysiology and Natural History of Non Alcoholic Fatty Liver and Non
Alcoholic Steatohepatitis Invited lecture at the 2004 Joint Annual Meeting
of the Swiss Society for Gastroenterology and Hepatology and the Swiss
Society of Visceral Surgery, Montreux, Switzerland, 9-11 September 2004.
Cortez-Pinto, H. Non-alcoholic fatty liver – iron metabolism”. In the Session: “Nature or

nurture in liver disease: whose guilty is it?” Invited lecture at the 26th European Society of
Enteral and Parenteral Nutrition (ESPEN), Lisbon, Portugal, 9-11 September 2004.
Cortez-Pinto, H. Moderator of the Session: “Global Overeating – a novel epidemic”. 26th

European Society of Enteral and Parenteral Nutrition (ESPEN), Lisbon, Portugal, 11-14
September 2004.
Cortez-Pinto, H. Moderator of the Poster Session: “Miscelaneous 1”. 26th European Society of
Enteral and Parenteral Nutrition (ESPEN), Lisboa, Portugal, 11-14 September 2004.
Cortez-Pinto, H. Oxidative stress in NAFLD”: here does it come from without the alcohol?
Invited lecture at the EASL Monothematic Conference: “Non-Alcoholic steatohepatitis: from
cell biology to clinical practice”. Estoril, Portugal, 17-18 September 2004.
Cortez-Pinto, H. How I became a rising star”. In the Young Investigators Workshop: “How to
set up, perform and present a study. Invited lecture at the interactive course for young European
Investigators, during the United European Gastroenterology week (UEGW) 2004. Prague, Czech
Republic, 26-29 September 2004.
Cortez-Pinto, H. NASH. Invited lecture in the State of the art liver lectures session of the United
European Gastroenterology Week (UEGW) 2004, Prague, Czech Republic, 26-29 September
2004.
Cortez-Pinto, H. Moderator of the “Lunch Session”: NASH/ASH. In the United European

Gastroenterology Week (UEGW) 2004, Prague, Czech Republic, 26-29 September 2004.
Cortez-Pinto, H. Encefalopatia. Invited lecture in the Session: “Complicações da cirrose”,

during the 17º Curso de Doenças Hepatobiliares, Coimbra, Portugal, 15-16 October 2004.
Cortez-Pinto, H. Moderator of the session: “Sindroma metabólica e interazione con HCV”. In

the meeting: “Síndrome metabólica fegato e HCV”, organizado pela Universidade de Modena,
Modena, Italy, 19-20 November 2004.
Cortez-Pinto, H. Esteatohepatite. Invited conference at the Curso de Actualização em

Hepatologia – Reunião conjunta de Hepatologia do Hospital Central do Funchal e a APEF,
Funchal, 4 December 2004
Lourenço, R. Lecture “Taurine” in a Symposium on Parenteral Nutrition “Structokabiven”

organized by Fresenius-Kabi. Porto Santo, Portugal, March 2004.
Lourenço, R. Lecture “Drug-induced fluid and electrolyte imbalances”. 26th Congress of the
September 2004.
Lourenço, R. Moderator of the “Pharmacist’s” and of the “Water and Electrolytes” round tables,
and of 2 Guided poster sessions on “Nutritional Pharmacology” and “Miscellaneous”. 26th
Portugal, 11-14 September 2004.
Marques-Vidal P. Lecturer: “Exercise to counteract muscle wasting in the elderly”. 26th Congress
of the European Society for Clinical Nutrition and Metabolism (ESPEN), Lisbon, Portugal, 11-14
September 2004.
Monteiro Grillo, I. Discusiones de docencia. Experiencia en Portugal 3as Jornadas Oncológicas

Internacionales- La Oncología Radioterápica en el Tercer Milenio. Madrid 17-19 June 2004.
Monteiro Grillo, I. Terapêutica Oncológica. Radioterapia. Curso de Formação em Tecnologias

da Saúde, Direcção Geral de Saúde. Ministério da Saúde. 4 November 2004.
Monteiro Grillo, I. Oftalmopatia Tiroideia XLVII Congresso Português de Oftalmologia, Viseu

2-4 December 2004.
Moura Santos, P. Moderator of the round tables: “Ageing and Nutrition” and “Nutrition and
AIDS”, and of a guided poster session on “Liver and Gastrointestinal tract”. 26th Congress of the
September 2004.
Ravasco, P. Lecture: “Podem alguns nutrientes melhorar a evolução do doente oncológico?”

integrado no Simpósio Satélite NOVARTIS intitulado “Novos nutrientes em oncologia: um
futuro prometedor!” no XX Congresso Nacional da SENPE (Sociedade Espanhola de Nutrição
Parentérica e Entérica), Salamanca, Spain, 5-8 May 2004.
Ravasco, P. Lecture: “Nutrição definições e conceitos” integrado no Workshop de Nutrição

Clínica: “Definições, conceitos e realidade” promoted by APNEP (Associação Portuguesa de
Nutrição Entérica e Parentérica) and ANID, Lisbon, Portugal, 27 May 2004.
Ravasco, P. Moderator of the round table: “Key issues of malnutrition in cancer: the
therapeutical approach”, and lecturer: “European recommendations on food and nutrition:
implications for oncologic care”. 26th Congress of the European Society for Clinical Nutrition
and Metabolism (ESPEN), Lisbon, Portugal, 11-14 September 2004.
Ravasco, P. Lecture: “Can specific nutrients improve the prognosis of oncologic patients?” in the
Session: “Key papers in the field of Clinical Nutrition”. 26th Congress of the European Society for
Clinical Nutrition and Metabolism (ESPEN), Lisbon, Portugal, 11-14 September 2004.
Ravasco, P. “A alimentação como forma de prevenção da doença” integrado no X Encontro “A

alimentação e a família – Programa de Educação Alimentar” promovido pela Câmara Municipal
de Oeiras, Auditório do Centro de Apoio Social de Oeiras, 18 October 2004.
The following Investigators of the Unit were among the key Organizers of the Annual ESPEN
(European Society for Clinical Nutrition and Metabolism) 26th Congress held in Lisbon, 11-14
September 2004:
Camilo, ME - President of the Congress and member of ESPEN Central Executive

Committee during 2004.
Camilo, M.E. - Co-Organization of the post-graduate 11th ESPEN Course in Clinical

Nutrition and Metabolic Care held in Warsaw, Poland, 15-20 October 2004.
Lourenço, R. - Chairman of the local Educational and Clinical Practice Committee and
member of the corresponding Central Committee during 2004.
Cortez-Pinto, H. EASL Monothematic Single Topic Conference: Non-Alcoholic steatohepatitis:

From cell biology to clinical pratice, Estoril, Portugal, September, 17-18, 2004.
Monteiro Grillo, I. - Chaired the 1º Congresso Nacional da Sociedade Portuguesa de Radioterapia

Oncologia, Cascais, Maio 2004.
Monteiro Grillo, I. - Chaired the 1º Curso de Braquiterapia Prostática de Alta Taxa de Dose,
Novembro 2004.
Monteiro Grillo, I. - Scientific Commitee. 23rdAnnual ESTRO Meeting Amsterdam, Outubro de

2004.
Ravasco, P. - Organization of the Program of the 2004 APNEP Annual Meeting (Portuguese
Association for Enteral and Parenteral Nutrition), Lisbon, 14 September 2004.
Prizes
Marques-Vidal P, Dias CM. The communication "Trends in the prevalence of diagnosed diabetes
in Portugal". won second place (posters) in the Meeting of the Working Group on Epidemiology
and Prevention of the European Society of Cardiology, Elsinore, Denmark, June 2004.
Ravasco, P., Monteiro Grillo, I., Pinto, R., Camilo, M.E. “Cancro Colorectal: citocinas e
deterioração nutricional durante a Radioterapia”. Awarded the Prize for the best original work
presented in the Congress (Congresso Nacional da Sociedade Portuguesa de Radioterapia e
Oncologia).
Ravasco, P. Nominated and selected by the World Scientist Forum of the International Research
Promotion Council to be awarded the International prize “Eminent Scientist of the Year 2004” in
the area of Science and Medicine, specifically in Nutrition and Clinical Oncology. Recent
Advances and Research Updates, Vol. 5, Nº3, December 2004.
Camilo, M.E.: Faculty of the 11th ESPEN Course in Clinical Nutrition and Metabolic Care held in
Warsaw, Poland, 15-20 October 2004.
Lecture- “Prevention and Treatment of Malnutrition”;
Case-based approach Workshop and interactive session on “Nutritional management of a patient

with acute cardiopulmonary failure in an Intensive Care Unit”.
Cristina, I.: "Nutrição parentérica - vias de administração e composição" in the Workshop –

“Nutrição Clínica”, V Congresso Nacional da Associação Portuguesa de Farmacêuticos
Hospitalares (Portuguese Association of Hospital Pharmacists), Lisboa, Portugal, 24 November
2004.
Marques-Vidal P. “Epidemiology and sociology of exercise”. Master’s degree teaching at the

Faculdade de Motricidade Humana of the Universidade Técnica de Lisboa (total time: 30 hours).
Monteiro Grillo, I. “Tratamento da dor em cuidados paliativos”. II Curso de Mestrado em

Cuidados Paliativos, Faculdade de Medicina de Lisboa, 2004.
Monteiro Grillo, I. Ensino pré-graduado, Módulo C, Clínica Universitária Cirurgia II, Faculdade
de Medicina de Lisboa (2004/05).
Ravasco, P.: “Farmaconutrientes: um futuro prometedor?”, in the Workshop “Nutrição Clínica” V

Congresso Nacional da Associação Portuguesa de Farmacêuticos Hospitalares (Portuguese
Association of Hospital Pharmacists), Lisboa, Portugal, 24 November 2004.
Ravasco, P.: “Nutrição e Oncologia: a experiência do Serviço de Radioterapia”, Serviço de

Radioterapia do Hospital de Santa Maria, Lisboa, Portugal, 25 March 2004.
Thesis Completed
Master Thesis
Mil-Homens, M.J. (2004) “Caracterização da actividade física da população adulta portuguesa e

sua relação entre os estado de saúde e os custos com cuidados medicos”. Mestrado em Exercício
e Saúde, Cruz Quebrada: Universidade Técnica de Lisboa. Supervisor: Marques-Vidal, P.
Pereira, P.J.C.C. (2004) “Actividade física e aptidão física associada à saúde em adolescentes de
ambos os sexos com idades entre 13 e os 18 anos”. Mestrado em Exercício e Saúde, Cruz
Quebrada: Universidade Técnica de Lisboa; 2004. Supervisor: Marques-Vidal, P.
Diploma Thesis
Marques, J.M.P. (2004) “Estudo comparativo da aptidão física dos jovens escolarizados do
concelho de Montemor-o-Velho”. Licenciatura em Educação Física e Desporto, Universidade
Lusófona de Humanidades e Tecnologias, Lisboa. Supervisor: Marques-Vidal, P.
Sousa, N.L. (2004) “Estudo do papel da actividade física na prevenção das doenças
cardiovasculares: relação da actividade física e factores de risco das doenças cardiovasculares e
seus efeitos na população idosa”. Licenciatura em Educação Física e Desporto, Universidade
Lusófona de Humanidades e Tecnologias, Lisboa. Supervisor: Marques-Vidal P.
Tomé, I.M. (2004) “Relação entre hábitos alimentares, de actividade física e marcadores da
obesidade nos adolescents”. Licenciatura em Educação Física e Desporto, Universidade Lusófona
de Humanidades e Tecnologias, Lisboa. Supervisor: Marques-Vidal, P.
Costenla, M.M.dM. (2004) “Avaliação dos comportamentos e conhecimentos alimentares dos

utentes da consulta de Endocrinologia, Diabetes e Metabolismo do Hospital de Santa Maria”.
Licenciatura em Nutrição e Engenharia Alimentar, Instituto Superior de Ciências da Saúde – Sul,
Monte de Caparica. Supervisor: Marques-Vidal, P.
Martelo, R.M. (2004) “Caracterização da alimentação de utentes com diabetes tipo 2 do Centro
de Saúde de São João - Lisboa. Estudo da alimentação de uma amostra de idosos”. Licenciatura
em Nutrição e Engenharia Alimentar, Instituto Superior de Ciências da Saúde – Sul, Monte da
Caparica. Supervisor: Marques-Vidal P.
Portela, H.J.F.R. (2004) “Cancro da próstata: factores nutricionais e antropométricos”.

Licenciatura em Nutrição e Engenharia Alimentar, Instituto Superior de Ciências da Saúde – Sul,
Monte de Caparica. Supervisor: Marques-Vidal, P.
Oncology Programme
Molecular Pathobiology Unit
Lage, P, R. Sousa, C. Albuquerque, P. Chaves, M. Salazar, M. Cravo, C. Baltazar, R. Fonseca, I.

Claro, A. Suspiro, P. Rodrigues, H. Raposo, P. Fidalgo, C. Nobre Leitão (2004). Polipose
Hiperplásica: Caracterização Fenotípica e Molecular de Uma Entidade Rara com Risco
Aumentado de Cancro do Cólon e Recto. GE - Jornal Português de Gastrenterologia 11(2):76-83.
Claro, I., S. Ferreira, P. Lage, I. Francisco, C. Albuquerque, P. Chaves, A. Suspiro, L. Maia, P.

Rodrigues, H. Raposo, M. Cravo, P. Fidalgo, C. Nobre- Leitão (2004) Valor dos critérios de
Bethesda na identificação de novos casos de síndroma de Lynch em famílias sem critérios de
Amsterdão. GE – Jornal Português de Gastrenterologia 11(3):122-127.
Albuquerque, C., C. Baltazar, B. Filipe, R. Smits, T. Pereira, F. Penha, P. Lage, M. Cravo, P.

Fidalgo, I. Veiga, J. Silva Ramos, R. Fodde, I. Fonseca, C. Nobre Leitão. Increased frequency of
TCF-4 mutations in colorectal tumors presenting β-catenin mutations: possible role in the
regulation of β-catenin/TCF-4 signaling. Jornal da Sociedade Portuguesa de Ciências Medicas (In
press).
Books/Book Chapters
Foroni L, Gameiro P, Hoffbrand AV, Minimal residual disease in acute leukemia. Chapter 33 in
Post-Graduate Hematology, edited by AV Hoffbrand, D Catovsky, 5th edition, 2004.
Agapito, A., F. Fonseca, J.R. Andrade, B. Cavaco, V. Leite, L. Gardete Correia. Neoplasia
endócrina múltipla tipo 1-caso clínico. 55ª Reunião da Sociedade Portuguesa de Endocrinologia,
Diabetes e Metabolismo, Granja, 2004.
Almeida, A., I. Claro, E. Rosa, R. Carvalho, E. Santos, M. Cravo. Deterioration of nutritional

status during hospital stay in surgical patients with gastrointestinal (GI) cancer: a prospective
study. (Poster) 26 th ESPEN, 11-14 September 2004.
Almeida, A., I. Claro, E. Rosa, R. Carvalho, E. Santos, M. Cravo. Nutritional support in surgical
patients with gastrointestinal cancer (GI): an urgent need for specific guidelines. (Poster) 26th
ESPEN, 11-14 September 2004.
Domingues, R., Sobrinho, L., Bugalho, M.J. “Germline mutations of the RET proto-oncogene in
80 Portuguese patients with medullary thyroid carcinoma”. 12th International Congress of
Endocrinology, Lisbon, 31 August - 4 September 2004.
Espadinha, C., B. Cavaco, I. Correia, C. Igreja, S. Constantino, S. Dias, L. Sobrinho, V. Leite.

Estimulação do crescimento celular pela oncoproteína PAX8-PPARγ nas células Nthy-ori-3.1.
55ª Reunião da Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo, Granja, 2004.
Ferreira, S., I. Claro, P. Lage, R. Fonseca, M. Salazar, R. Sousa, A. Suspiro, P. Rodrigues, P.

Fidalgo, I .Fonseca, C. Nobre-Leitão. Prognostic analysis differs in patients with colorectal
cancer according to its aetiology: Sporadic, HNPCC or familial adenomatous polyposis. UEGW
– 12th United European Gastroenterology Week, Prague, 25-30 September 2004.
Fragoso, R. and Sérgio Dias. “A Role for FLT-1 in Acute Lymphoblastic leukemia”. 4th European
Conference on Angiogenesis. 21-24 May 2004 Helsinki (Finland).
Igreja, C., Margarida Courinha, Maria G Silva and Sergio Dias. “Novel AC133 isoforms
distinguish circulating from incorporated AC133 cells during tumor growth”. Poster Presentation
at the 46th Meeting of the American Society of Hematology San Diego, USA, December 2004.
Marques, A.R., C. Espadinha, M.J. Frias, L. Roque, A.L. Catarino, A. Pinto, V. Leite. Expressão
do peroxisome proliferatos-activated receptor (PPAR) γ em neoplasias da tiróide. 55ª Reunião
Anual da Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo, Granja, 2004.
Machado, P. Correlation between the results of genetic screening for BRCA1/2 mutations and
Immunostainingfor the BRCA1/2 proteins (Poster). European Human Genetics Conference 2004.
Munich, Germany, June 2004.
Patarrão, R.S., M.P. Guarino, N.C. Correia, R.T. Ribeiro, R.A. Afonso, A.I. Santos, V. Leite,
J.M. Boavida, W.W. Lautt, M.P. Macedo.A sensibilidade à insulina em humanos é dependente da
HISS. 6º Congresso Português de Diabetes, Porto, 2004.
Patarrão, R.S., W.W. Lautt, M.P. Guarino, R.A. Afonso, R.T. Ribeiro, N.C. Correia, A.I. Santos,
V. Leite, J.M. Boavida, M.P. Macedo. Human insulin sensitivity regulation by prandial status.
12th International Congress of Endocrinology, Lisboa, 2004.
Rodrigues, R., Roque, L., Krug, T., Dias, S., Soares, J. Correlation of expression and
comparative genomic hybridization analysis of anaplastic and poorly differentiated thyroid
carcinoma cell lines. 12th International Congress of Endocrinology, 31 August-4 September 2004,
Lisbon, Portugal. (Poster)
Rodrigues, R., Roque, L., Pinto, A., Leite, V., Domingues, R., Nunes, V., Soares, J.
Chromosomal imbalances and BRAF mutations in aneuploid papillary thyroid carcinomas. 30 th
Annual Meeting of the European Thyroid Association, 18 – 22 September 2004, Istanbul, Turkey
(Poster)
Sancho, M., J. Vieira, S. Dias, V. Leite. CCR7 expression is increased in thyroid carcinomas
prone to lymph node metastasis. 12th International Congress of Endocrinology, Lisboa, 2004.
Salazar, M., I. Claro, P. Lage, S. Ferreira, B. Filipe, I. Francisco, C. Albuquerque, P. Chaves, M.

Cravo, P. Fidalgo, C. Nobre-Leitão. Colorectal cancer in young patients follows mainly the
mutator pathway only under the age of 35. UEGW – 12th United European Gastroenterology
Week, Prague, 25-30 September 2004.
Sousa, R., P. Lage, I. Francisco, C. Albuquerque, J. Dinis, I. Claro, M. Cravo, P. Fidalgo, C.

Nobre-Leitão. New germ-line mutations in MLH1 and MSH2 genes in hereditary non-polyposis
colorectal cancer. UEGW – 12th United European Gastroenterology Week, Prague, 25-30
September 2004.
Sousa, R., P. Lage, J. Monteiro, C. Albuquerque, J. Cabeçadas, M. Mesquita, I. Claro, J. Midões,

C. Nobre-Leitão. Complete response of gastric malt lymphoma to H Pylori eradication in the
presence of the T(11:18)(Q21;Q21) translocation. UEGW – 12th United European
Gastroenterology Week, Prague, 25-30 September 2004.
Sousa, C. Guerreiro, M. Brito, P. Marques Vidal, M. Cravo, C. Nobre-Leitão. Polymorfism of

APC gene at codon 1822 modifies susceptibility for colorectal câncer (CRC) according to fat and
calcium intake. (Communication and Poster) 26th ESPEN, 11-14 September 2004.
Valongueiro, I., S. Mão Ferro, M. Cravo, I. Claro, M. Salazar, S. Ferreira, P. Fidalgo, C. Nobre-
Leitão. High intake of unsaturated fat in patients with Crohn´s disease is associated both to
overweight and to chronic relapsing disease. (Communication and Poster) 26 th ESPEN, 11-14
September 2004.
Vaz, F. Perceived Risk of Breast Cancer and Health Promotion Behaviour in Women Seeking
Genetic Counselling for Breast Cancer (Poster Discussion Session) 29th European Society of
Medical Oncology Congress, Viena, Austria, October 2004.
Vieira, J.M., S.C.R. Santos, C. Casalou, B.M. Cavaco, S. Dias, V. Leite. A potential autocrine
role for vascular endothelial growth factor in thyroid tumours of follicular origin. 12th
International Congress of Endocrinology, Lisboa, 2004.
Vieira, L., Marques, B., Cavaleiro, C., Ambrósio, A.P., Joege, M., Alaíz, H., Diamond, J., Neto,
A., Santos, C., Júnior, E.C. Pereira, J.M., Boavida, M.G. Assessment of ETV6 gene involvement
by fluorescence in situ hybridization in three novel chromosome 12q rearrangements in
hematological malignancies. 9th Meeting of the European Hematology Association, Geneve,
June 2004.
Vieira, S., Deininger, M., Parreira, A., Melo, J.V. The BCL6 gene is a transcriptional target of
the BCR-ABL oncogene. FEBS Lecture Course on Cellular Signaling. Croácia, 21-27 May 2004.
Domingues, R., Garrão, A., Sobrinho, L., Bugalho, M.J. “Resistência às hormonas tiroideias: a
propósito de dois casos clínicos”. 55ª Reunião Anual da Sociedade Portuguesa de
Endocrinologia, Diabetes e Metabolismo, Granja, 23-25 January 2004.
Ferreira, S., Claro, I., Lage, P., Martins, C., Tristan, J., Albuquerque, C., Baltazar, C., Chaves, P.,
Rodrigues, P., Fidalgo, P., Nobre Leitão, C. Novo sindroma familiar de polipose gastrintestinal
associada a quebra cromatídica no cromossoma 3p21. XXIV Congresso Nacional de
Gastrenterologia e Endoscopia Digestiva, 2-5 Junho, 2004, Figueira da Foz, Portugal (Oral
communication)
Ferreira, S., I. Claro, P. Lage, C. Martins, R. Gonçalves, J. Tristan, C. Albuquerque, C. Baltazar,

P. Chaves, P. Rodrigues, P. Fidalgo, C. Nobre Leitão. Novo sindroma familiar de polipose
gastrointestinal associada a quebra cromatídica no cromossoma 3p21. XXIV Congresso

Nacional de Gastrenterologia e Endoscopia Digestiva, 2-5 June 2004, Figueira da Foz.
Filipe, B., I. Francisco, C. Albuquerque, P. Lage, R. Sousa, M. Salazar, I. Claro, A. Suspiro, P.

Rodrigues, H. Raposo, M. Cravo, P. Fidalgo, C. Nobre Leitão. HNPCC With Endometrial Cancer
In Portuguese Families Raises The Probability of Finding Pathogenic Mutations in Mismatch
Repair Genes Mainly in MSH2 Gene. (Poster) XIII Porto Cancer Meeting on Mismatch repair
genes, Microssatellite instability and Cancer, 3-4 May 2004, IPATIMUP, Porto.
Fragoso, S., C. Albuquerque, I. Vitoriano, C. Baltazar, S. Mão de Ferro, P. Lage, M. Cravo, P.

Fidalgo, C. Nobre Leitão. Nova abordagem no diagnóstico genético de síndromas hereditários de
cancro colorectal- gene MYH. 8ª Reunião da Sociedade Portuguesa de Genética Humana 18-19
November 2004, Porto.
Francisco, I., C. Albuquerque, B. Filipe, R. Sousa, P. Lage, M. Cravo, P. Fidalgo, C. Nobre

Leitão. Mutações activadoras na β-catenina em tumores de síndroma de Lynch são indicativas de
alterações germinais no gene MLH1. (Poster) 8ª Reunião da Sociedade Portuguesa de Genética
Humana 18-19 November 2004, Porto.
Francisco, I., C. Albuquerque, P. Lage, M. Salazar, R. Sousa, I. Claro, A. Suspiro, L. Maia, P.

Rodrigues, H. Raposo, M. Cravo, P. Fidalgo, C. Nobre-Leitão. High detection of mutations in
portuguese HNPCC families and different phenotypic profile in those with positive genetic
diagnosis. (Poster) XIII Porto Cancer Meeting on Mismatch repair genes, Microssatellite
instability and Cancer, 3-4 May 2004, IPATIMUP, Porto.
Lage, P., R. Sousa, J. Monteiro, C. Albuquerque, J. Cabeçadas, M. Mesquita, J. Midões, C .Nobre

Leitão. Resposta completa do linfoma gástrico MALT após erradicação do Helicobacter pylori
na presença da translocação t(11:18)(q21;q21). XXIV Congresso Nacional de Gastrenterologia,
Figueira da Foz, June 2004.
Mão de Ferro, S., P. Fidalgo, P. Lage, S. Fragoso, C. Baltazar, C. Albuquerque, I. Vitoriano, P.

Rodrigues, C. Nobre Leitão. Probabilidade de Detecção de Mutações no Gene MYH em
Genogramas de “Tipo Recessivo”. XXIV Congresso Nacional de Gastrenterologia e Endoscopia
Digestiva, 2 a 5 de June 2004, Figueira da Foz.
Mão de Ferro, S., P. Fidalgo, P. Lage, S. Fragoso, C. Baltazar, C. Albuquerque, I. Vitoriano, P.

Rodrigues, C. Nobre Leitão. Adenomas múltiplos do cólon e análise do gene MYH:
caracterização fenotípica e avaliação do risco de neoplasia. XXIV Congresso Nacional de
Gastrenterologia e Endoscopia Digestiva, 2-5 June 2004, Figueira da Foz.
Mão de Ferro, S., P. Lage, P. Fidalgo, S. Fragoso, C. Albuquerque, C. Baltazar, I. Vitoriano, P.

Rodrigues, C. Nobre Leitão. Polipose associada ao MYH: fenótipo grave na homozigotia para a
mutação 1103delC e risco em heterozigotos. XXIV Congresso Nacional de Gastrenterologia e
Endoscopia Digestiva, 2-5 June 2004, Figueira da Foz.
Salazar, M., P. Lage, S. Ferreira, B. Filipe, I. Francisco, R. Fonseca, C. Albuquerque, I. Claro, A.

Suspiro, P. Rodrigues, M. Cravo, P. Fidalgo, I. Fonseca, C. Nobre-Leitão. Síndroma de Lynch
com critérios de Amsterdão: A instabilidade de microssatélites não deve constituir um marcador
intermediário para a análise mutacional. XXIV Congresso Nacional de Gastrenterologia,
Figueira da Foz, June 2004.
Salazar, M, I. Claro, P. Lage, S. Ferreira, B. Filipe, I. Francisco, C. Albuquerque, P. Chaves, M.

Cravo, P. Fidalgo, C. Nobre Leitão. Carcinoma do cólon ou recto em jovens: predominância da
via mutadora apenas em idade inferior a 35 anos. XXIV Congresso Nacional de
Gastrenterologia, Figueira da Foz, June 2004.
Sousa, R., P. Lage, I. Francisco, C. Albuquerque, J. Dinis, I. Claro, M. Cravo, P. Fidalgo, C.

Nobre Leitão. Detecção de novas mutações germinais nos genes MLH1 e MSH2 em Síndroma de Lynch.
XXIV Congresso Nacional de Gastrenterologia, Figueira da Foz, June 2004.
Sousa Guerreiro, C,. M. Brito, P. Marques-Vidal, M. Cravo, C. Nobre-Leitão. O polimorfismo do

gene APC 1822 associado a um aumento do consumo de gorduras aumenta a susceptibilidade
para o CCR. XXIV Congresso Nacional de Gastrenterologia, Figueira da Foz, June 2004.
Sousa Guerreiro, C., P. Marques-Vidal, M. Cravo, C. Nobre-Leitão. O consumo de cálcio está

negativamente relacionada com o risco de cancro colorectal: estudo caso-controlo. XXIV
Congresso Nacional de Gastrenterologia, Figueira da Foz, June 2004.
Vieira, J., S. Constantino, C. Casalou, S. Dias, V. Leite. Loop autócrino do factor de crescimento
do endotélio vascular em células tumorais da tiróide. 55ª Reunião da Sociedade Portuguesa de
Endocrinologia, Diabetes e Metabolismo, Granja, 2004.
Albuquerque, C. Doença Heredo-Familiar: Poliposes. 10th Oncology Multidisciplinary Meeting,

15 April 2004, Hotel Altis, Lisboa.
Bugalho MJ. “Avanços da Biologia Molecular no diagnóstico de Síndromes Neoplásicos

Endócrinos Familiares. Carcinoma Medular Familiar”. Reunião da Sociedade Portuguesa de
Endocrinologia e Diabetologia Pediátrica, Lisbon, 26 November 2004.
Bugalho, M.J. “Cirurgia profiláctica no carcinoma medular da tiroideia, integrado na Mesa

Redonda Internacional sobre Cancro Hereditário e Cirurgia Profiláctica”. XXIV Congresso
Nacional de Cirurgia, Culturgest, Lisboa, 7-10 March 2004.
Cravo, M. Nutrition, Just do it Right. 26th ESPEN Congress, 11-14 September 2004.
Dias, S. “Endothelial Differentiation”. Principal Investigator Seminar at Instituto Gulbenkian

ciencia, 13 July 2004.
Dias, S. “Molecular basis for Endothelial Differentiation and Tumor Angiogenesis”. Meeting of
the European Society for Microcirculation. Lisbon, 9 September 2004.
Dias, S. “Angiogenesis in hematologic malignancies”. Meeting of the GELA (“Groupe dÉtude

des Lymphomes de lÁdulte”), Strasbourgh, France, 14-16 October 2004.
Dias, S. “Angiogenesis in Hematological Malignancies”. Annual Meeting of the Portuguese

Society of Hematology. Carvoeiro, Algarve, November 2004.
Cravo, M. Organization and President of the Scientific Comitee of the 26th ESPEN Congress, 11-
14 September 2004.
Vaz, F., organized the Chemoprevention Conference included in: 5º Curso Pós-Graduado de
Oncologia Médica. Mesa Redonda: Relevância da Quimioprevenção em Patologia Oncológica
frequente. IPOFG, CROL, SA, April 2004, Lisboa, Portugal.
Prizes
Albuquerque, C., C. Baltazar, B. Filipe, R. Smits, T. Pereira, F. Penha, P. Lage, M. Cravo, P.

Fidalgo, I. Veiga, J. Silva Ramos, R. Fodde, I. Fonseca, C. Nobre Leitão. Prize Maria Amélia de
Mello para as Ciências da Saúde 2004 – Honor Mention: Increased frequency of TCF-4 mutations
in colorectal tumors presenting β-catenin mutations: possible role in the regulation of β-
catenin/TCF-4 signaling.
Marques, A.R., C. Espadinha, M.J. Frias, L.Roque, A.L. Catarino, A. Pinto, V. Leite. First Prize
on Basic Research by the Portuguese Endocrine Society 2004 for the work “Expression of
peroxisome proliferator-activated receptor (PPAR)γ in thyroid neoplasias”.
Mão de Ferro, S., P. Lage, P. Fidalgo, S. Fragoso, C. Albuquerque, C. Baltazar, I. Vitoriano, P.

Rodrigues, C. Nobre Leitão. Prize Melhor Caso Clínico do XXIV Congresso Nacional de
Gastrenterologia e Endoscopia Digestiva, 2-5 June 2004, Figueira da Foz: Polipose associada ao
MYH: fenótipo grave na homozigotia para a mutação 1103delC e risco em heterozigotos.
Salazar, M., I. Claro, P. Lage, S. Ferreira, B. Filipe, I. Francisco, C. Albuquerque, P. Chaves, M.

Cravo, P. Fidalgo, C. Nobre-Leitão. Prize Abstract Award 2004 on UEGW – 12th United
European Gastroenterology Week, Prague, 25-30 September 2004: Colorectal cancer in young
patients follows mainly the mutator pathway only under the age of 35
Sousa, R., P. Lage, I. Francisco, C. Albuquerque, J. Dinis, I. Claro, M. Cravo, P. fidalgo, C.

Nobre-Leitão. Prize Abstract Award 2004 on UEGW – 12th United European Gastroenterology
Week, Prague, 25-30 September 2004: New germ-line mutations in MLH1 and MSH2 genes in
hereditary non-polyposis colorectal cancer.
Susana Constantino Rosa Santos and Sérgio Dias. Pfizer Award (15,000 Euro) in Biomedical
Research, October 2004. (ex-aecquo)
Susana Constantino Rosa Santos and Sérgio Dias. Prémio Pulido Valente (10,000 Euro) for
Research in Oncobiology, 2004.
Bugalho, M.J. “Introdução à Oncobiologia e à Medicina Preventiva do Cancro” - Ciclo de

Colóquios sobre Medicina Preventiva do Cancro. Lisbon, Fundação Calouste Gulbenkian, 1
March 2004.
Bugalho, M.J. “Introdução à Oncobiologia e à Medicina Preventiva do Cancro” - Ciclo de

Colóquios sobre Medicina Preventiva do Cancro. Porto, Fundação Serralves, 19 October
Dias, S. “Oncogenicidade”, Ciclo de Cursos Avançados em Oncologia, IPOFG, 22 April 2004.
Dias, S. "Angiogénese e Cancro" Class given for the Masters Degree in Oncobiology
(IPATIMUP). Porto, 16th December 2004.
Dias, S. Oncogenesis and Metastasis Course. PDGB (PhD Program) of the Instituto Gulbenkian
Ciência. Oeiras, 1-5 March 2004. (organizer since 2002)
Dias, S. Class included in the Seminars for the “Teaching of Oncology Research”. "Angiogénese
e Cancro", IPOFG (Lisboa), 25-26st July 2002.
Dias, S. “Molecular basis for Endothelial Function”. 5th Cell:Materials interaction course, INEB,
Porto. 7-9 July 2004.
Gameiro, P.. “Molecular Investigation of minimal residual disease in acute leukaemia”, PGDB
doctoral program. Instituto Gulbenkian de Ciência. Oeiras, Portugal, 3 March 2004.
Vaz, F. Cancro da Mama Hereditário. Symposium: Medicina Preventiva do Cancro: Interacção

genético-ambiental: das teorias à prática. Organização: Fundação Calouste Gulbenkian e
IPATIMUP, Lisboa, Portugal, May 2004.
Vaz, F. Women’s cancers: prevention, diagnosis and treatment. Escola Superior de Emfermagem
de Franscisco Gentil, Lisboa, Portugal, Novembro de 2004.
Vaz, F. Cancro da Mama Hereditário. Simpósio sobre Medicina Preventiva do Cancro:

Interacção genético-ambiental: das teorias à prática. Organização: Fundação Calouste
Gulbenkian, Fundação Serralves e IPATIMUP, Novembro de 2004.
Thesis Completed
Diploma Thesis
Maria Isabel Lopes Correia (2004) “Characterization of mutations in B-raf, PIK3CA and Pax8-
PPARγ in thyroid neoplasias”. Tese de Licenciatura em Bioquímica, Faculdade de Ciências da
Universidade de Lisboa. Supervisor: V. Leite
Maria Margarida Sancho (2004) “2-Role of chemokines in the metastasising pathways of thyroid
carcinomas”. Tese de Licenciatura em Bioquímica, Faculdade de Ciências da Universidade de
Lisboa. Supervisor: V. Leite
Sofia Fragoso (2004) “Nova abordagem no diagnóstico genético de síndromas hereditários de

cancro colorectal- gene MYH”. Tese de licenciatura em Química Aplicada à Biotecnologia.
Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa. Supervisor: Cristina
Albuquerque
Maria Inês Vitoriano (2004) “Novo Síndroma recessivo do cancro do cólon e recto - gene MYH”
e “Via de sinalização RAS/RAF na tumorigénese colorectal”. Tese de licenciatura em Bioquímica.
Faculdade de Ciências da Universidade de Lisboa. Supervisor: Cristina Albuquerque
Vera Borrego (2004) “Identificação de novos casos de HNPCC em indivíduos sem critérios de
Amsterdão utilizando os critérios de Bethesda”. Tese de licenciatura em Química Aplicada à
Biotecnologia. Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa. Supervisor:
Cristina Albuquerque
Patrícia Silva (2004) “Caracterização das alterações genéticas envolvidas na via

hiperplásica/serreada de tumorigénese”. Tese de licenciatura em Bioquímica. Faculdade de
Ciências da Universidade de Lisboa. Supervisor: Cristina Albuquerque
Patrícia Machado (2004) “Rastreio de rearranjos nos genes BRCA em famílias portuguesas com
Síndroma Hereditário de Cancro da Mama/Ovário”. Tese de licenciatura em Química Aplicada,
Ramo Biotecnologia, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa.
Supervisor: Fátima Vaz

ActivityReport IMM2004

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IMM – Report | 1

IMM- Past, Present and Future____________________________________ 3

IMM- Science & Society__________________________________________ 5

IMM- Cell & Dev. Biology Programme______________________________ 7

IMM- Immunology & Inf. Diseases Programme______________________ 33

IMM- Neurosciences Programme___________________________________ 53

IMM- Oncology Programme_______________________________________ 87

IMM- Indicators ________________________________________________ 110

IMM- Detailed R&D Activities_____________________________________ 111

IMM – Past, Present and Future

João Lobo Antunes, MD, PhD – President

José Ferro, MD, PhD

Margarida Pinto Gago, Administrator & Finance Officer

IMM – Science & Society

2. EDAB International Brain Awareness Week (15-21 March 2004)

3. Workshops for Secondary School Teachers

Maria Francisca Wright de Menezes Ferreira: “Educational Resources on the Internet”. I

Maria Francisca Wright de Menezes Ferreira: “Semana Internacional do Cérebro 2004 -

Maria Francisca Wright de Menezes Ferreira: “Neurocientistas do IMM Contribuem para o

Cell and Developmental Biology Programme

Cell Biology Unit

Description and Objectives

Maria Carmo-Fonseca, MD, PhD – Full Professor, FML

José Francisco David Ferreira, MD, PhD - Professor Emeritus, FML

Cell and Molecular Biology

Recent Most Relevant Publications

Carmo-Fonseca, M., Mendes-Soares, L., and Campos, I. (2000) To be or not to be in the

Carmo-Fonseca, M. (2002) The contribution of nuclear compartmentalization to gene regulation.

Ongoing Research Projects

2001/05 RNOMICS: An integrated analysis of links between pathways of RNA

2002/05 TRI-EX: Oculopharyngeal muscular dystrophy – a paradigm to investigate new

2004/09 MOLECULAR IMAGING: Integrated technologies for in vivo molecular

2004/06 Profiling alternative splicing in muscular dystrophies (MDA3662)

Biogenesis of messenger RNA (mRNA) involves transcription of precursor molecules (pre-

Publications in International Journals (2004)

Braga J., Desterro J.M., Carmo-Fonseca M. (2004) Intracellular macromolecular mobility

Hematopoietic Biology Unit

Description and Objectives

In the Unit of Hematopoietic Biology we investigate the biological mechanisms underlying

Leonor Parreira, MD PhD – Full Professor, FML

LINE I - Hematopoietic Differentiation

Leonor Parreira – PI (MD, PhD)

Since October 2004 – Ornella Preisner – PhD student

Line II - Signal Transduction in T-cell leukemia and T-cell development

Coordinator: João Taborda Barata, PhD – Post-Doc fellowship, FCT

Recent Most Relevant Publications

Alcobia I, Dilao R, Parreira L (2000) Spacial associations of centromeres in the nuclei of

Ongoing Research Projects

Line I – Hematopoiesis Group

2001/05 Differential effects of Notch ligands Delta 1 and Jagged1 in lymphoid

2003/06 Delta and Jagged genes in normal hematopoietic differentiation.

Line II – Tumor Biology Group

2000/04 Targeting signaling pathways as therapy for human cancer

Publications in International Journals (2004)

Chromatin Biology Unit

Description and Objectives

João Ferreira, MD, PhD – Auxiliary Professor, FML

Soren Steffensen (Jan-Sept 2004), PhD – Post-Doc Fellowship, FCT

Cell and Molecular Biology

Recent Most Relevant Publications

Ongoing Research Projects

2000/04 Cell Biology of Human topoisomerase IIa. Fundação para a Ciência e a