Factitious acute hypercalcemia biological interference between calcium and lipids.
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Biomedical subjects
Publications and source records attributed to J Dormont.
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The association between thrombocytopenic thrombotic purpura (TTP) and infectious or multisystem disease, pregnancy, transplantation, drugs and toxins is well known. The onset of TTP in the course of neoplasm is rarely described. The authors report one case of TTP associated with prostatic tumor. TTP preceded the discovery of neoplasm by 12 months. Moreover, TTP showed an original course with four recurrences despite antiplatelet and hormonal therapies; the successive regressions were obtained with less and less effort, as TTP was discovered at an early stage.
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The occurrence of hyperchloremia during diabetic ketoacidosis (DKA) recovery and the lack of correlation between anion gap excess (delta AG) and bicarbonate deficit (delta TCO2) on admission suggest an hyperchloremic acidosis (HCLA) component. The hypothesis that this phenomenon is not specific of DKA and can occur in other metabolic acidoses with increased anion gap was tested. HCLA component, defined by the ratio delta AG/delta TCO2 less than or equal to 0.80, was evaluated on admission and during therapy in 31 patients with DKA and 53 patients with non diabetic metabolic acidosis (ND-MA). HCLA component prevalence was similar on admission (32 p. 100 for DKA versus 41 p. 100 for ND-MA), but it increased during therapy only in DKA patients (86 p. 100 at 9 h - P less than 0.001). In view of the significant correlation (r = 0.636; P less than 0.001) observed between delta AG/delta TCO2 and creatinine, kidney acid base defense appears clearly in DKA patients: the more severe the volume depletion, the greater the ketone retention and the less prominent the HCLA. This phenomenon seems to be secondary to a large tubular excretion of ketones. In the 53 ND-MA patients no correlation between delta AG/delta TCO2 and creatinine could be found. A transfer of chloride from cells to the extracellular space secondary to intracellular diffusion of lactate ions could explain the HCLA component.
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Certain system diseases which include vascular involvement may be accompanied by pulmonary artery hypertension (PAHT). This chiefly concerns connective tissue disorders, notably scleroderma, CREST syndrome and mixed connective tissue disease and, to a lesser extent, systemic lupus erythematosus. The onset of PAHT in relation to vasculitis of the great vessels or necrosing angeitis is rare. It may result from pulmonary artery vasoconstriction of hypoxic origin during diffuse interstitial pulmonary fibrosis, a thrombo-embolic mechanism, a vasomotor phenomenon equivalent at pulmonary level to Raynaud's syndrome, and above all from pulmonary vasculitis, the commonest mechanism. The incidence of PAHT is such connective tissue disease is probably underestimated since it is a complication often unrecognised clinically. It is a major cause of death in such conditions, certain of which nevertheless enjoy a benign reputation. With the exception of rare cases of favourable outcomes under the influence of corticosteroids and immunosuppressants in cases of mixed connective tissue disease, no treatment has in fact been shown to be effective in terms of survival.
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To document the in vivo interactions occurring between the immune system and HIV replicating cells, we analyzed using in situ hybridization the production of IL-1 beta, IL-6, IL-2, and INF-gamma in eight hyperplastic lymph nodes from HIV-1 infected patients. Numerous IL-1 beta- and IL-6-producing cells associated in clusters were detected in sinuses. Few individual IL-1 beta- and IL-6-producing cells were present in interfollicular and follicular areas. IL-2- and INF-gamma-producing cells were observed in all lymph node compartments, with a selective enrichment in germinal centers. The amount and distribution of IL-1 beta, IL-6-, and IL-2-producing cells in HIV lymph nodes were not different from those found in six HIV unrelated hyperplastic lymph nodes. In contrast, a higher level of INF-gamma production was observed in HIV-1 lymph nodes. The CD8+ cells that accumulate in germinal centers of HIV lymph nodes (and not in non-HIV germinal centers) were actively involved in this INF-gamma production. INF-gamma synthesizing cells were in direct contact with cells containing HIV core antigens and HIV RNA. Thus a high INF-gamma production may characterize anti-HIV T cell immune response, potentially contributing to control of viral spreading as well as to the development of follicle lysis.
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Intravenous gammaglobulin (IVIgG) was given to seven adults with chronic idiopathic thrombocytopenic purpura (ITP). In parallel with platelet count, we studied Con A induced suppressor cell function for the autologous in vitro B cell response, T cell subsets and PAIgG levels, immediately before and 3-4 d after completion of treatment. Before treatment all patients had normal T cell subsets, decreased T suppressor cell function and increased levels of PAIgG. After IVIgG infusions, two patients were unresponsive and neither suppressor cell function nor PAIgG levels varied. In contrast, in the five responding patients we found an improvement in suppressor cell function and a decrease in PAIgG levels, while T cell subsets remained unmodified. Such results were reproducible in three patients after a second series of gammaglobulin infusions. Our results support the hypothesis that IVIgG infusion, apart from its effects on the reticuloendothelial system, may modulate the immune response by enhancing suppressor T cell function.
New methods allow the study of humoral immunity in man using blood lymphocyte cultures. A primary in vitro antibody response can be induced, characterized by the appearance of antibody forming cells, and its pattern is as follows: stringent culture requirements, which have been so far obtained in few laboratories; the kinetics of the response, with a peak on day 7--8; and exclusively IgM response; a T-cell requirement. Among these methods, the model we have described has the advantage of allowing a reproductible response in a given individual. The in vitro study of humoral immunity has limitations, the most apparent of which is that it addresses itself to only one lymphoid population, that in peripheral blood, easily accessible. It presents several advantages, as compared to an in vivo study after injection of an antigen: absence of ethical problem; the necessity of only one blood sample, at a given time, avoiding the interference of a treatment started after the test; the possibility of performing successive primary stimulations for a longitudinal study.
A localised outbreak of trichinosis occurred in January 1976 in the southern suburbs of Paris. A total fo 125 cases was recorded including 30 children. The prominent symptoms were oedema of the face or eyelids, fever, and myalgia; diarrhoea was unusual and constipation common. An increased blood eosinophil count and raised serum concentrations of muscular enzymes strongly indicated trichinosis. This diagnosis was confirmed later immunologically. The parasite was found in only three out of 32 muscle biopsy specimens but this investigation was made relatively early in the disease. No deaths occurred. In all cases clinical recovery was fast and serum antibody titres were maximum during the first month and decreased slowly. The disease was milder and the recovery faster in children than adults. Epidemiological study suggested that horse meat was responsible for the infection, though no meat could be examined.
The role of macrophages in the in vitro response of mouse spleen cells to the insolubilized, T-independent antigen trinitrophenylated polyacrylamide (TNP-PAA) is demonstrated by the following points. The response is abolished by filtration on Sephadex G-10 and can be restored by the addition of splenic adherent cells, deficient in either B or T cells, or by 2-mercaptoethanol (2ME). It is suppressed upon elimination of phagocytic cells by silica, and restored by 2-ME. 2-ME can restore a normal response from zero, in cultures depleted of both adherent and phagocytic cells, and is efficient in the absence of mature T cells. Experiments in microcultures show that large numbers of macrophages can stimulate a supra-optimal response from B cells. This response is only obtained in the presence of the antigen, and is specific for TNP. These results show that microphages, probably by their polyclonal B-cell activator (PBA) property, play a role in the specific response to TNP-PAA. This prompts us to discuss the respective roles in the B-cell response of this PBA activity and of the interaction of the antigen with the specific B-cell receptors.
We have studied the primary in vitro antibody response toward a hapten in cultures of peripheral blood lymphocytes from twenty-two patients suffering from regular rheumatoid arthritis (RA). These patients were not receiving immunosuppressive drugs or corticosteroids and had not taken Aspirin or non-steroidal anti-inflammatory agents for at least 72 hr. The control groups included thirty-two healthy subjects and twenty-seven control patients. The mean anti-TNP response of the RA patients was significantly lower than that of both control groups. No pre-existing anti-TNP or IgG response could be detected. A search for suppressor cells in co-cultures of RA and normal lymphocytes was negative. On the contrary, the extent of allogeneic enhancement in such co-cultures was comparable to that observed when control lymphocytes were co-cultured. RA serum added to normal lymphocytes cultures showed a dramatic inhibitory effect in only two out of nine cases. A follow-up study has strongly suggested that RA lymphocytes could increase their in vitro antibody response upon treatment.
We have studied the in vitro antibody response to a hapten of peripheral blood lymphocytes from 26 patients with rheumatoid arthritis and 7 ankylosing spondylitis. These patients had never received immunosuppressor drugs before or corticosteroids during the month before the test. They had failed to receive aspirin or non-steroid anti-inflammatory drugs for 72 hours before blood sampling. The control groups included respectively 38 healthy subjects and 24 patients hospitalized for non inflammatory disease. The antibody response of ankylosing spondylitis patients is comparable to that of controls ; on the opposite the response of patients with rhumatoid arthritis is significantly depressed in comparison with the three other groups. The weak response of lymphocytes in arthritis is not due to increased cell death in culture or to modified kinetics of the antibody response or to the appearance of a IgG secondary type response or a in vivo pre-activation. The lymphocytes of arthritis patients do not inhibit the response of normal lymphocytes when they are co-cultured. The observed response is identical to that obtained when control patient lymphocytes are co-cultured with normal lymphocytes. The function of suppressor T cells induced by Con A seems normal in spondylitis and arthritis.
The specific response of human peripheral blood lymphocyte cultures to TNP-polyacrylamide was suppressed by the addition of concanavalin A (Con A). A dose of Con A (0.5 microgram/ml) could be selected, which induced a reproducible but incomplete suppression independent of the magnitude of the anti-TNP response. Con A-stimulated cells could transfer the suppression to autologous or allogeneic responding cells. The suppressor activity was present in the E-rosette forming cell fraction and was abolished by mitomycin C treatment prior to incubation. With a particular batch of foetal bovine serum, spontaneous suppressor cells were produced which suppressed the response of autologous and allogeneic lymphocytes. In allogenic mixtures, the otherwise enhancing allogeneic effect was replaced by a marked suppression from spontaneous suppressor cells. This suppression was higher than that exerted on autologous lymphocytes, suggesting that an unexpected negative allogenic effect had taken place. Spontaneous suppressors were ineffective when added on day 2 of a culture responding to TNP-polyacrylamide, whereas Con A induced suppressors were fully effective.
Balb/c mice were immunized with dog insoluble glomerular basement membrane (GBM) or tubular basement membrane (TBM). The titre of circulating antibodies was sequentially determined and their specificity was analysed using various soluble membrane fractions. Glomerular and tubular deposits were studied on serial biopsies by direct immunofluorescence. After elution, from whole kidneys, IgG fixation on normal mouse kidney sections was analysed by indirect immunofluorescence. The conclusions are the following: (a) after immunization with insoluble GBM, the antibodies are mainly directed against collagenous antigenic determinants shared by GBM and TBM; (b) after immunization with insoluble TBM, the antibodies are mainly directed against noncollagenous TBM-specific antigenic determinants.