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M Carmo-Fonseca

Publications and source records attributed to M Carmo-Fonseca.

81 records · Page 5Linked to original sources
PubMed1984

Quantitative analysis of pore patterns on rat prostate nuclei using spatial statistics methods.

Spatial statistics methods have been used to analyse the nuclear pore pattern in rat ventral prostate nuclei isolated from adult animals. The observed results show that: (1) pores on prostate nuclear membranes are not randomly distributed; (2) the data sets obtained from different micrographs are consistent with the same statistical model thus suggesting the existence of a typical pore distribution.

Animals↗
PubMedDate not supplied

Triplet repeats, RNA secondary structure and toxic gain-of-function models for pathogenesis.

Ten years after the discovery of human diseases caused by trinucleotide repeat expansions, searching for mechanistic links between gene mutation and pathological phenotype remains a fundamental and unsolved issue. Evidence accumulated so far indicates that the pathogenesis of repeat disorders is complex and multi-factorial. Diseases caused by CAG expansions coding for polyglutamine tracts have been extensively studied, and in most cases a toxic gain-of-function of the mutant protein was demonstrated. Most recently, tracking the effects of repeats along the pathway of gene expression is providing additional clues to understand how a triplet repeat expansion can cause disease. Expanded repeats form DNA secondary structures that confer genetic instability, and most likely contribute to alter the local chromatin configuration leading to transcriptional silencing. At the level of RNA, the expanded repeat may either interfere with processing of the primary transcript, resulting in deficit of the corresponding protein, or interact with RNA-binding proteins altering their normal activity. The latter mechanism, termed RNA gain-of-function, has no precedents in human genetics. Recent evidence suggests that expanded RNAs and associated RNA-binding proteins are potential contributors to the pathogenesis of several triplet repeat diseases.

Amino Acid Sequence↗
PubMedDate not supplied

Quality control of gene expression in the nucleus.

Proteins are responsible for most cellular and extra-cellular functions. If altered, proteins can loose their normal activity and/or gain new properties. Either way the consequences may be deleterious for the cell and lead to disease at the organism level. Not surprisingly, eukaryotes have evolved mechanisms to recognize abnormal messenger RNAs and prevent them from producing faulty proteins. Protein-encoding genes are transcribed in the nucleus by RNA polymerase II as precursor RNAs that undergo extensive processing before being translocated to the cytoplasm for translation by the ribosomes. This spatial and temporal separation between RNA and protein synthesis offers an immense opportunity for control and regulation. Here we review recent studies that are beginning to unravel how the coupling between transcription, processing and transport of mRNAs contributes to control the quality of gene expression in the nucleus.

Cell Nucleus↗
PubMedDate not supplied

Histology of the synovial tissue: value of semiquantitative analysis for the prediction of joint erosions in rheumatoid arthritis.

OBJECTIVE: Routine histologic techniques are still the main procedure in the study of the synovial biopsy. The relationship between the typical histological changes of rheumatoid synovium and clinical manifestations has not been studied in detail. METHODS: With the aim of determining whether a simple semiquantitative method of evaluating the changes in closed synovial biopsies was of clinical value in assessing both the diagnosis and prognosis of rheumatoid arthritis (RA) patients, we evaluated retrospectively 72 synovial biopsy specimens (26 RA patients, 30 patients with other inflammatory diseases and 16 osteoarthritis patients). Scores (0-10) were assigned to each biopsy specimen for each of 6 histologic features: synoviocyte hyperplasia; fibrosis in the subsynovial layer; proliferating blood vessels; perivascular infiltrates of lymphocytes; focal aggregates of lymphocytes; and diffuse infiltrates of lymphocytes. Scores were compared between the 3 groups and also between the RA subgroups with early and late disease; positive and negative rheumatoid factor; with and without joint erosions; and with and without systemic disease. RESULTS: Significant differences in the mean global score (mean of the 6 scores) were found both between RA and osteoarthritis and between other inflammatory diseases and osteoarthritis (p < 0.01). The mean global score for RA was higher than the mean global score obtained for the other inflammatory diseases, but the difference was not significant. We found a significantly higher mean global score in the RA patients with erosions in comparison to the RA patients without erosions, this difference being particularly evident for the lymphocyte perivascular infiltrate (p < 0.05). There were no significant differences between the other RA subgroups. CONCLUSION: In this study we have identified differences, using routine histologic techniques, between the rheumatoid synovial membrane of patients with and without erosions. Based on our present observations we suggest that the intensity of inflammatory histological features and, in particular, a high percentage of vessels with perivascular lymphocyte infiltrate might be of prognostic value in RA.

Aged↗
PubMedDate not supplied

Inflammatory cell infiltrate and RANKL/OPG expression in rheumatoid synovium: comparison with other inflammatory arthropathies and correlation with outcome.

OBJECTIVES: To evaluate if the immunofluorescence analysis of synovial tissue (ST) using antibodies against RANKL/OPG, conjugated with the immunophenotyping of lymphocytes and macrophages, could be of diagnostic and prognostic value in rheumatoid arthritis (RA) patients. METHODS: 3-year prospective study of 103 consecutive patients submitted to closed needle biopsy for diagnostic purposes. ST was analyzed with routine histologic techniques and immunofluorescence, using monoclonal antibodies against RANKL, OPG, CD163, CD68, CD4, CD8, interferon-gamma and CD19. Patients were prospectively evaluated with a clinical, laboratorial and radiological protocol. At the end of the follow-up patients were divided according to the final diagnosis. Results of the initial histologic evaluation were compared between the main diagnostic groups and in RA patients histologic data was correlated with clinical and radiologic outcome measures. RESULTS: The RANKL/OPG ratio and the inflammatory infiltrate were significatively higher in RA (n = 25) as compared to the same ratio observed in other inflammatory joint diseases (OIJD, n = 48) and in osteoarthritis (n = 17). The difference between RA and OIJD was specifically confirmed when the comparison involved spondyloarthropathy (n = 26). Final HAQ score and radiologic outcome were correlated with the density of intimal CD68+ macrophages. Radiologic progression was correlated with subintimal CD4+ lymphocytes and CD68+ macrophages and intimal CD68 and CD163+ macrophages. CONCLUSION: The quantification of the RANKL/OPG ratio and of the number of lymphocytes in the ST might be useful to differentiate RA from other inflammatory joint diseases. The ST number of CD4+ lymphocytes and macrophages are probable predictors of radiologic progression in RA patients.

Aged↗
PubMedDate not supplied

[Intracellular recognition mechanisms. Physiopathologic implications].

The cell has two distinct organelle systems specialized in the sorting of membranes molecules: the Golgi complex for outward (exocitic) membrane traffic and the endosomal system for inward (endocytic) membrane traffic. Receptor mediated endocytosis allows the cell to internalize specific molecules like LDL, Fe, growth factors and IgA. Within the cell these molecules can follow different pathways, while their receptors are recycled to the plasma membrane.

Cell Compartmentation↗
PubMedDate not supplied

Reinnervation of post-arthritic joints in the rat.

OBJECTIVE: To clarify the role of articular innervation during the acute and post-arthritic phases, we investigated the changes taking place over time in the nerve fibers from joint tissues of adjuvant arthritic rats. METHODS: Nerve densities (i.e., the number of nerve fibers observed per unit area of tissue section) were estimated in periarticular tissues, synovium and epiphysis from ankle joints. Nerves were identified by immunofluorescence microscopy using antibodies against general neuronal markers (Protein Gene Product 9.5, synaptophysin, neurofilaments and Schwann cells), and markers specific for either sensory or sympathetic nerves (Substance P, calcitonin gene related peptide, neuropeptide tyrosine and its C-terminal flanking peptide, and the catecholamine synthesising enzyme tyrosine hydroxilase). RESULTS: In arthritic rats, the density of nerve fibers in the periarticular tissues, epiphysis and synovium was significantly reduced when compared to control animals. This decrease was observed using antibodies for both non releasable neuronal products (Protein Gene Product 9.5, synaptophysin, neurofilaments and Schwann cells) and neuropeptides (Substance P, calcitonin gene related peptide, neuropeptide tyrosine and its C-terminal flanking peptide), thus suggesting the existence of a structural nervous lesion with the parallel depletion of peptides. As the clinical arthritis subsided, there was a progressive reinnervation of all the articular structures analysed, which often exceeded the density of nerves in the control animals. CONCLUSION: This work supports a close relationship between the nervous system and arthritis. We propose that cycles of nerve destruction and regeneration may be related to the characteristic periods of remission and activity of some forms of chronic arthritis.

Acute Disease↗