Evidence for B cell oligoclonality in the blood and joints of patients with rheumatoid arthritis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Monteiro.
Explore the source record for details and available documents.
The role of T cells in chronic lymphocytic leukemia (CLL) has not been extensively investigated, since the most prominent cellular abnormality in CLL involves the clonal expansion of B cells. In this study we have undertaken a comprehensive analysis of the CD4+ and CD8+ T cell repertoire in a population of CLL patients (n = 19) and age-matched controls (n = 22). The TCR repertoire analysis was performed using a multiplex PCR assay for CDR3 length, an approach that allows for the detection of underlying oligoclonality in complex T cell populations. We established that oligoclonality was substantially more frequent in both the CD4+ and CD8+ T cell populations of CLL patients than in the age-matched controls (p < 0.001). Using three-color FACS analysis with a panel of TCRV segment-specific mAbs, we also established that oligoclonal expansions are predominantly found in the CD57+ subset of both the CD4+ and CD8+ T cell populations. The frequency of the CD57 marker on CD4+ T cells was increased in the setting of CLL (% CD57 = 14.8 +/- 13.0%) compared with that in normal controls (% CD57 = 3.3 +/- 3.0%; p < 0.001). An elevated frequency of CD4+CD57+ T cells was correlated with more advanced disease. Similarly, the most extreme oligoclonal expansions of CD4+CD57+ T cells occurred in CLL patients who had progressed beyond Rai stage 0. These data document profound alterations in the T cell repertoire of CLL patients and point to a role for clonal T cell populations in the pathogenesis of this disease.
Arthroplasty with poly(methyl methacrylate) (PMMA) bone cement induces late loosening phenomena that compromise the prosthetic stability. As free radicals are inflammatory mediators and cytotoxic, it seemed useful to investigate whether PMMA induces the liberation of free radicals and/or cytotoxicity. The effect of PMMA interaction on cultured human fibroblasts was accessed by the cell viability test (MTT), and by the measurement of lipoperoxides in the incubation medium. The incubation with the medium exposed to PMMA induced a significant reduction in the viability and a significant increase in lipoperoxide liberation (vs control). These data suggest that PMMA is cytotoxic. This effect seems to be mediated by lipoperoxide and possibly by other free radicals, and may explain the peri-implant loosening phenomena that compromise the prosthetic stability.
The exercise tolerance test (ETT) is the ancillary test of choice for the evaluation of the patient with ischaemic heart disease. When faced with complaints suggestive of angina pectoris, ETT is useful in confirming or excluding such a diagnosis, frequently reproducing the complaints while recording the tell-tale electrocardiographic signs of ischaemia--ST segment deviation. Additionally, the ETT provides information on the severity of the disease and is also valuable for the risk stratification of future coronary events. This information as a whole can be used both in the diagnosis and in the management of the patient with coronary artery disease.
The occurrence of angina pectoris in patients with normal coronary angiograms is a subject of investigation since its first description as an entity in 1967. Its etiology remains unknown but, in the absence of disease of the epicardial coronary arteries, dysfunction of the small, most distal vessels and the endothelium appear to be incriminated. In this review, the most recent knowledge and understanding of the pathophysiology, clinical presentation and management of this syndrome is presented.
INTRODUCTION: Inflammatory changes are relatively frequent findings in cervical smears and are generally believed to be a consequence of genital infection. However, clinical signs of infection are frequently absent and no consensus exists on the management of these patients. The objective of this study was to assess whether or not inflammatory smears are exclusively a consequence of genital infection. For this purpose, the prevalence of genital infection in a group of women with inflammatory cells in the cervical smear and a control group with normal smears was compared. MATERIAL AND METHODS: Sixty-two regularly menstruating women aged 17 to 48 years, attending the outpatient Gynaecology sector of S. João Hospital, were prospectively evaluated. Cervical smears were analysed by the same cytologist who chose 10 inflammatory cells per high power field (400x) as the cut-off value for normality. Infection by Candida spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis and bacterial vaginosis was investigated. Human Papillomavirus infection was evaluated by colposcopy and biopsy of abnormal colposcopic findings. RESULTS: Thirty-four women and inflammatory cells on their cervical smear and 15 of these (44%) had a genital infection. Of the 28 women with normal smears, 12 (43%) had a genital infection. No statistically significant difference in the prevalence of infection was found between the two groups. CONCLUSIONS: Our results suggest that the presence of inflammatory cells in cervical smears is not necessarily due to infection and other causes may be responsible for their appearance.
Explore the source record for details and available documents.
Long term in vitro culture of clonally expanded CD8+T cells, generally found within the CD57+ or CD28-subset, has generally been unsuccessful, suggesting that these cells may have a limited replicative potential. Telomeric shortening may reflect the action of a "mitotic clock" regulating the number of divisions a cell can undergo. In this study, we have compared the telomeric lengths of CD28-CD8+ and CD28+CD8+ T cells in 10 normal individuals to assess their replicative history. Overall, the telomeric lengths were found to be significantly shorter in the CD28-CD8+ T cell subset compared with the CD28+CD8+ subset. Furthermore, clonally expanded TCRBV11+CD8+ T cells from an individual exhibited telomeric lengths that were 2.9 kb shorter than those found in the polyclonal CD28+CD8+ T cell subset. These findings indicate that clonally expanded CD28-CD8+ T cells have undergone many more rounds of replication than CD28+CD8+ T cells, and consistent with the loss of CD28 expression, they may have reached a state of replicative senescence.
It has been established that oligoclonal expansion is a common feature of the CD8+ T cell population, particularly within the CD8+ CD57+ lymphocyte subset. In addition, clonal malignancies involving CD8+ CD57+ T cells (large granulocytic lymphocytic leukemias) are often accompanied by rheumatoid arthritis, Felty's syndrome, or both. Therefore, to identify disease-related alterations in the CD8+ T cell repertoire, we have compared the patterns of oligoclonality in the CD8+ T cells of rheumatoid arthritis patients (n = 32) with those of age-matched controls (n = 25). By using a multiplex PCR assay for the CDR3 length of TCR beta-chains, we have found a striking increase in the frequency of CD8+ oligoclonality involving V beta 3 TCR: 50% of the rheumatoid arthritis patients had evidence of oligoclonality in this TCR family compared with 4% of controls (p < 0.0002). In addition, two unrelated RA patients had clonally dominant CD8+ T cell beta receptors that were identical in amino acid sequence, suggesting selection by a common Ag. An analysis of a subset of RA patients with mAbs specific for V beta 3 TCR revealed the presence of clonal expansion in a minority of patients usually, but not exclusively, involving the CD57+ subset. These data define a phenotype of the T cell repertoire that is strongly associated with rheumatoid arthritis; the mechanisms and genetic and environmental factors that explain this phenomenon remain to be defined.
Approximately 60 cases of spinal angiolipomas have been described in the medical literature. Extradural tumours predominate. Lesions with a bony component, the infiltrating subgroup, were reported in 10 patients. Intradural angiolipomas were found three times. Several excellent review articles are available, but a systematic comparison of the characteristics of the two major varieties, infiltrating and non-infiltrating spinal extradural angiolipomas, has not so far been made. The authors operated on two patients with spinal angiolipomas and found one of them the infiltrating and the other the non-infiltrating type. Then, they proceeded to a review of all publish cases of infiltrating angiolipomas. With a knowledge of recently reported data on the subject the authors compared essential clinical features of both varieties of tumours. They share identical clinical characteristics. Differences found in age, sex or location were not statistically significant. Mode of onset and signs and symptoms present on admission were essentially similar. As could be anticipated, removal was more often complete in non-infiltrating tumours, but outcome was good or fair in more than 85% of cases in both groups. Involvement of bone by spinal angiolipomas does not imply a worsening in the prognosis.
We have shown earlier that CD8+ T cell oligoclonality occurs frequently in normal individuals and general exhibits a very diverse repertoire. In order to investigate the role of CD8+ T cells in MS, we analysed CD8 oligoclonality in 125 patients with MS in varying stages of disease. A multiplex PCR assay for CDR3 length variation was employed to detect oligoclonality in 25 TCRBV segments/families. CD8 clonal dominance was found to be frequent in MS. Comparison of the CD8 T cell repertoire in MS with that in normal controls revealed an increased frequency of oligoclonality involving the TCRBV9, -18 and -23 families. Sequence analysis of the TCRs from these clonally dominant CD8+ cells revealed a high degree of diversity overall. However, we observed one instance of identical TCRBV18 sequences in CD8 cells from two unrelated MS patients. In addition, several TCRs with motifs homologous to those found in MS brain and MBP specific T cell clones in EAE and MS were also detected. Future characterization of the function and specificity of these clonally expanded populations may provide insight into the nature of immune dysregulation in this autoimmune disorder.
Cerebral Metastases are diagnosed in approximately 20-30% of patients with primary tumours. Because of the improvement of central nervous system imagining technology and of the newly effective therapeutic schemes, the incidence of this particular type of cerebral lesion tends to increase. In this retrospective study the authors review the patients admitted in the Neurology, Neurosurgery and Medicine departments and in the outpatient chemotherapy consultation, with a diagnosis of cerebral metastases. Sex and age, neurologic symptoms at presentation, neuroradiologic findings, primary tumour origin, treatment outcomes and prognosis were evaluated in this population.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: To evaluate the heart disease associated to different type and sub-types of cerebrovascular disease with particular reference to potential cardiac sources of embolus (CPE). DESIGN: Prospective study in 248 consecutive patients with acute stroke, admitted to a Clinical Medicine Unit in three independent time periods. SETTING: Internal Medicine Clinic of University Hospital in Lisbon. METHODS: Neurologic and cardiologic examination were performed and all patients were also submitted to different complementary tests, including a Computer Tomography Scan of the brain (TAC) and a Echocardiogram (ECO). We identified two types and two sub-types: intracerebral haemorrhage (HI) or ischemic stroke (AI) and among AI, cortical (C) or subcortical (SC) ischemic stroke. For each type and sub-type we evaluated past history, heart disease, hypertension (HTA), electrocardiogram, echocardiogram (ECO) and CPE. PATIENTS: Two hundred and forty eight patients (52% were men) with mean age 68.0 +/- 10.2 years and ages between 40 and 92 years. Thirty seven (15%) died. MAIN RESULTS: Eighty four percent were AI and among them 45% were C. Previous strokes were more prevalent in AI 29% (p < 0.01). There was heart disease in 81% and hypertensive cardiopathy was more frequent in HI 63% (p < 0.002). HTA and atrial fibrillation (FA) were more frequent in HI 83% (p < 0.05) and in AI 25% (p < 0.004) respectively. ECO showed a dilatation of left atrium more frequent in AI 28% (p < 0.05) and left ventricular concentric hypertrophy index (IHCE) in HI 50% (p < 0.05). CPE, including FA, was identified in 34% of patients, was more prevalent in AI 38% (p < 0.001) and among it FA was significantly more frequent in C 32% (p < 0.02). CONCLUSIONS: Heart disease is very frequent in stroke. The diagnosis of this condition is very important for stroke prophylaxis and prognosis. HTA and hypertensive cardiopathy have a great prevalence and were more related to HI. CPE and FA were very frequent and their diagnosis are important for prevention of AI and specially for embolic stroke. ECO is useful to identify CPE in elderly patient in particular to characterize heart disease.