CSF T lymphocytes in multiple sclerosis.
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Biomedical subjects
Publications and source records attributed to A Franco.
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The effectiveness of antibiotic prophylaxis was evaluated in the immediate postoperative period of renal transplantation (RT). Before RT, the patients were randomly assigned to one of the following groups: 1) cefotaxime (intravenous infusion of 1 g one hour before the operation). 2) Ceftriaxone (1 g i.v. given in a similar way). 3) Control (without antibiotics). Patients who required antibiotic therapy during the first 3 postoperative weeks were excluded. 20 recipients of cadaveric renal grafts were included in each group. There were 39 males and 21 females with a mean age of 39.9 years. One patient from the cefotaxime group (5%), 2 from the ceftriaxone group (10%) and 2 from the control group (10%) developed infection of the surgical wound, all due to grampositive organisms. 19 patients had urinary tract infections: 7 from the control group (35%), 7 from the cefotaxime group (35%), and 5 from the ceftriaxone group (25%). The development of wound infection was not correlated with urea, creatinine, hemoglobin or total protein levels, or with urinary tract infection or fistula, diabetes or fever. The mean packed red cell volume of the patients who developed wound infection was 24.7 +/- 1.2 vs 28.6 +/- 6.6 in those who did not (p less than 0.01). All patients with visible hematoma and 3 of 10 with perirenal blood collection had wound infection. It was concluded that antibiotic prophylaxis for renal transplantation was useless in our patients.
Vasoactive drugs are widely prescribed in France. Over the last few years, some of these molecules have been evaluated by controlled clinical trials based on subjective assessment of their effects on the arterial or venous disease. Paraclinical investigations performed with a view to provide clinical pharmacological or physiopathological information give an indication as to the mode of action of these drugs but cannot, under any circumstances, be substituted for controlled clinical trials implying the inclusion of large patient population groups.
In order to carry out this study, 62 embryos and fetuses of Friesian cows were used, and every stomach was dissected and subjected to the usual laboratory procedures. After obtaining each preparation all the histological and metrical changes that took place in the wall of the viscus during its development are described. The compartments are histologically differentiated into three stages: in the first one there is no compartment differentiation: in the second one, the rumino-reticulum, omasum and abomasum have differentiated; and in the third one every compartment is differentiated. In group 16, (78 days of gestation), a decrease in thickness of the muscular layer of all compartments, parallel to the histological differentiation has been observed.
CHO cells were transfected with cDNAs for all 4 subunits of the mouse muscle acetylcholine receptor (AChR) to obtain a stable cell line (CHO-AR) expressing the AChR on its surface. Immunoprecipitation experiments established that the AChR contained alpha- and beta-subunits assembled with gamma- and/or delta-subunits. In addition, one of the toxin-binding sites of the AChR was blocked by a myasthenic serum that specifically recognizes AChR containing the gamma-subunit. AChR from the CHO-AR cells had the same sedimentation rate, association rate constant for the binding of alpha-bungarotoxin (alpha BTX), and the same metabolic half-life as the AChR in myotubes of the mouse muscle cell line C2C12. Electrophysiological assay of CHO-AR cells by single-channel recording showed the presence of ACh-responsive ion channels with the characteristics of the embryonic AChR (gamma = 40 pS, tau = 5.6 msec). In some patches a smaller conductance channel was also seen that may represent partially assembled receptor. Fluorescence microscopy of fixed, permeabilized cells stained with rhodamine-alpha-BTX demonstrated both perinuclear and diffuse surface staining. The expression of fully assembled, functional mammalian muscle AChR in nonmuscle cells will allow detailed investigation of its properties and interactions with other cellular components.
The Ag specificity and cytotoxic function of human T cell clones, generated from lymphocytes infiltrating the liver of a chronic hepatitis B patient, were studied. Both class I- and class II-restricted T clones specifically proliferated to hepatitis B virus envelope proteins, but not to hepatitis B core Ag. The fine specificity of T cells was studied by using rAg having different composition in relation to HBV-envelope proteins or synthetic peptides of preS regions. The antigenic determinant recognized by T cell clones mapped to the preS2 region based on the response to r(preS1+preS2+S) and to r(preS2+S) and the failure to respond to S or preS1 alone. More precise epitope mapping was based on synthetic preS2 peptides 120-150 or 120-134, which stimulated both class I- and class II-restricted T clones, whereas preS2 153-171 or preS1 1-110 peptides did not; thus, the preS2 120-134 appears to contain both the residues binding to class I molecules and the residues binding to class II molecules. Moreover, strong and specific cytotoxic responses of these clones were observed only when HLA-matched EBV-lines, used as target cells, were previously sensitized with r(preS1+preS2+S) or preS2 peptides, which were shown to stimulate the clones. Thus, a preS2 epitope can represent a target Ag for liver-infiltrating T cells, which could kill the hepatocytes expressing the Ag plus the appropriate MHC molecule.
In this study, we evaluated the effect of ras oncogene activation on cell response to interferons (IFNs). For this purpose, we treated NIH 3T3 murine fibroblasts transformed by transfection with K-, Ha-, or N-ras oncogenes, either mutated or amplified, for 24 hours with IFN-gamma or IFN-alpha. We evaluated cell response by measuring virus replication, [3H]thymidine incorporation, 2',5'-oligoadenylate synthetase activation, and class I antigen induction. Transformed cells were much less responsive to IFN-gamma antiviral and antiproliferative activities than normal NIH 3T3 cells. Similarly, the induction of 2',5'-oligoadenylate synthetase following IFN-gamma treatment was completely depressed in transformed cells. Only class I antigens, measured at the cell surface and mRNA levels, appeared partially inducible by IFN-gamma in ras-transformed cells. When the same cell lines were treated with IFN-alpha, we observed full response. Because both normal and ras-transformed NIH 3T3 cells were able to bind [125I]IFN-gamma with comparable Kd values (8.3 X 10(-11) M vs. 3 X 10(-11) M, respectively), these findings suggest that ras oncogenes may differentially impair IFN-gamma activities by affecting activation of IFN-inducible genes downstream from the receptor binding event.
The effects of interferon-gamma (IFN-gamma) on protein synthesis of a pre-B cell leukemia, L1210, have been studied by two-dimensional gel electrophoresis. In total cell extracts, at least ten proteins were induced de novo, or increased in their expression, after an 18-h IFN-gamma treatment, whereas in the nuclear extracts eight proteins were specifically induced. Of these, increased synthesis of a 40-kDa/pI 5.9 cytoplasmic protein was the most prominent and reproducible. Most of these proteins appear to be specific for a defined step of differentiation, since they are not found in other B cell leukemias upon IFN-gamma treatment. Others appear to be tissue specific, since they are not induced in fibroblasts nor in T cells. In addition, synthesis of some of the induced proteins appeared to require rapid transcription of new mRNA, because actinomycin D markedly inhibited their formation when added immediately before IFN-gamma. In keeping with this finding, in vitro translation of mRNA from IFN-gamma-treated L1210 cells into a rabbit reticulocyte lysate system, followed by analysis of the labeled proteins by two-dimensional gel electrophoresis, revealed the appearance of at least seven proteins. Taken as a whole, these results demonstrate that in leukemic pre-B cells IFN-gamma induces the transcriptional activation of genes coding for cytoplasmic and nuclear proteins, some of which could be employed as specific cell activation markers.
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The lymphatic origin of chronic edema of the lower limbs was identified by lymphoscintigraphic exploration. Patients underwent therapy involving 8 days of manual lymph drainage combined with elevation of the limbs during rest periods and double compression bandaging. Manual drainage increased lymph flow in 16 limbs, implying that the edema resulted from a functional lymphatic anomaly. In contrast, manual drainage did not increase lymph flow in 9 limbs, suggesting a structural anomaly of the lymphatics. Hence, the same clinical picture corresponded to two different lymphatic anomalies, distinguished by lymphoscintigraphy. However, the therapeutic results were independent of the lymphoscintigraphic results. Increased lymph flow is therefore not the only explanation for the decrease in edema during therapy.
The work reported here examined the effects of smoking cigarettes made predominantly of dark tobacco, alcohol consumption, and coffee drinking upon the risk of developing cancers of the bladder, larynx, lung, and oral cavity/hypopharynx in Medellín, Colombia. For this purpose 439 subjects with newly diagnosed cancers at the indicated sites were selected. Each subject was then matched by age, sex, and socioeconomic status with at least one control. Data from interviews with the selected subjects, upon analysis, showed both the intensity and duration of cigarette smoking to be statistically significant predictors of cancer at all four sites. In addition, heavy alcohol consumption and coffee drinking in excess of seven cups daily were associated with some elevation of cancer risk at most of the sites studied. Multivariate analyses of cigarette smoking, alcohol consumption, and coffee drinking showed that adjustment for coffee and alcohol consumption did not change the observed associations between elevated cancer risks and cigarette smoking. However, adjustment of the coffee and alcohol consumption data for cigarette smoking reduced most of the observed relative risks of coffee and alcohol consumption and eliminated the statistical significance of certain associations.
We have previously shown that a mixture of three synthetic peptides (83.1, 55.1, 35.1), corresponding to fragments of the relative molecular mass 83,000 (83K), 55K and 35K Plasmodium falciparum merozoite-specific proteins, induces protection in Aotus triviroatus monkeys experimentally infected with P. falciparum. Here we describe two polymeric synthetic hybrid proteins based on these peptides that delay or suppress the development of parasitaemia in immunized human volunteers.
These studies were designed to investigate the characteristics of the intracellular messengers induced by interferons (IFN-alpha/beta and IFN-gamma) after receptor binding. Pretreatment of target cells with V. cholerae toxin, which is known to activate a membrane GTP-binding stimulatory protein (Gs), potentiated the action of IFN-gamma, but not of IFN-alpha/beta. By contrast, B. pertussis toxin, which is known to activate the GTP-binding inhibitory protein (Gi), had no effects on the action of both IFN-alpha/beta and IFN-gamma. Further support to the involvement of G proteins in IFN-gamma transduction signal came from the finding that a non-hydrolizable GTP analog, GTP-gamma-S, enhanced in the presence of phorbol esters (PMA) the antiviral and antiproliferative activity of IFN-gamma, but not of IFN-alpha/beta. On the other hand, forskolin or PGE1, known to increase the intracellular cAMP levels by different metabolic pathways, when added together with IFN-gamma, significantly potentiated its antiviral and antiproliferative activity. Pretreatment of the cultures with the above drugs completely prevented IFN-gamma activity. No effects were observed when forskolin or PGE1 were used with IFN-alpha/beta. Finally, the modulation of IFN-gamma activity by the above drugs was not a consequence of changes in the expression of the specific surface receptors, since [125I]IFN-gamma binding by pretreated target cells was comparable to that of untreated cultures. Altogether these results demonstrate that the IFN-gamma, but not the IFN-alpha/beta, transduction signal is mediated after receptor binding by a G protein with functional characteristics similar to those of the known Gs proteins. Activation of the adenylate cyclase system could be one of the subsequent steps involved in IFN-gamma action.
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Nailfold capillaries may be visualized in vivo using a simple non invasive microscopic technic. The assessment of capillary flow disturbances and organic microangiopathies is therefore rendered possible through capillary microscopy. Three kinds of clinically significant morphological abnormalities can be easily recognized: megacapillaries are huge capillaries with a diameter greater than 50 microns. They are mainly found in progressive systemic sclerosis and dermatomyositis, together with avascular areas and pericapillary edema; ramified capillaries are neovessels, most frequently related to subclinical cutaneous vasculitis; capillary hemorrhages may be induced either by active microangiopathies, or by deep vasomotor changes. The semiological consistency of these abnormalities makes capillary microscopy a valuable procedure for the early recognition of connective tissue diseases and the evaluation of vasomotor disturbancies in children as well as in adults. Further investigation of other microangiopathies like purpura rheumatica and diabetes are needed.
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