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Biomedical subjects

C Griscelli

Publications and source records attributed to C Griscelli.

At least 163 records · Page 9Linked to original sources

Regulation of prostaglandin E2 and plasminogen activator by various immunomodulators in human monocytes.

Mononuclear phagocyte populations and monocytes are able to produce, among numerous substances, a neutral protease, i.e. plasminogen activator (PA) and prostaglandins. Since it has been shown that prostaglandins (PGs) and particularly PGE2 could exert an inhibitory effect on PA production by macrophages, we have measured the in vitro production of PA and PGE2 by monocytes isolated from healthy donors. These monocytes were cultured either in the absence or the presence of various immunomodulators: lipopolysaccharide from E. coli, concanavalin A and RU 41740 or Biostim a broad spectrum immunostimulating agent isolated from Klebsiella pneumoniae (Cassenne Laboratories, France). The production of PGE2 was proportional to the number of monocytes per incubation, and at a given cell concentration varied greatly from one subject to another. When considering PGE2 productions, the type of the response to the different immunomodulators varied from subject to subject and ranged from stimulation to no effect, or even inhibition. Moreover, a statistically significant, inverse relationship exists between the spontaneous production of PGE2 and the effect of each immunomodulator. For a given subject, all agents always acted in the same way and there was an inverse relationship between the effects of the immunomodulators on plasminogen activator and PGE2 production.

Adjuvants, Immunologic↗

Longitudinal study of 18 children with perinatal LAV/HTLV III infection: attempt at prognostic evaluation.

We performed a longitudinal study (mean follow-up 19.5 months, range 3 to 42 months) in 18 consecutive children with clinical symptoms of LAV/HTLV III infection. Twelve patients were born to mothers infected with LAV/HTLV III, and six were infected by blood products administered during the first weeks of life. Immunologic studies included lymphocyte markers, in vitro responses to mitogens and antigens with corresponding skin tests, and antibody response with isoagglutinins, post-vaccination antibodies, and Candida. A serologic profile of antibody to GP110, P18, and P25 LAV/HTLV III antigens by radioimmunoprecipitation assay was also performed. The antigen-induced proliferative responses were normal in 10 patients who had a stable course, but were profoundly impaired in eight others who died or had poor condition with opportunistic infections. These in vitro measurements were well correlated with antigen skin tests. An abnormal antibody response to antigens, a low level of isoagglutinins, and a peculiar profile of LAV/HTLV III antibodies were also frequently observed in these eight patients. These measurements appear to be of prognostic value because they were noticed soon after onset of clinical symptoms.

Acquired Immunodeficiency Syndrome↗

Prostaglandin E2 and plasminogen activators in human milk and their secretion by milk macrophages.

Human milk was shown to contain prostaglandin E2 (PGE2) and plasminogen activator (PA) at variable concentrations depending on the time of lactation after delivery. Milk PA was functionally and immunologically identical to urokinase. A follow-up study showed that the maximum PGE2 concentrations occurred during the second week while the maximum PA concentration was observed at the end of the first week of lactation. Milk macrophages cultured in vitro were able to secrete both PGE2 and PA. When cells were activated by concanavalin A (ConA) or E. coli lipopolysaccharide (LPS), PGE2 secretion increased dramatically while PA secretion did not. The ability of activated macrophages to secrete PGE2 was at its highest shortly after delivery. It then progressively decreased during lactation. The possible physiological role of PGE2 and PA on the gastrointestinal tract of breast fed infants is discussed.

Concanavalin A↗

Specific binding of antigen onto human T lymphocytes.

Human T lymphocytes sensitized to Candida albicans (CA) were shown to proliferate in cultures induced with mannan, a ramified polysaccharide extracted from the cell well of CA. We presently describe that, when we used strongly labeled [3H]mannan, antigen-specific T blast cells were able to bind the labeled mannan on their membrane. The observations that irrelevant blast cells did not bind [3H]mannan, and that mannan-specific blast cells did not bind tritiated pneumococcal polysaccharide SIII, indicate the specificity of mannan binding. Mannan binding was reversible and saturable. Mannan binding on T blast cells was inhibited by preincubation with monoclonal antibodies to T3 but not to other T cell-related molecules. The characteristics of this receptor suggest its identity with the T cell receptor for antigen. The direct binding of mannan could be either due to a cross-linking of the receptor by multivalent mannan or to a recognition of mannan in association with HLA-DQ molecules, as suggested by partial blocking of mannan binding using anti-HLA-DQ monoclonal antibodies.

Adult↗

A monoclonal antibody specific for rat intestinal lymphocytes.

A monoclonal antibody, RGL-1, was produced by fusion of NSI myeloma cells with spleen cells of a mouse immunized with isolated rat intraepithelial lymphocytes (IEL). SDS-PAGE analysis revealed that RGL-1 precipitated two major noncovalently bound chains of about m.w. 100,000 and 125,000, and a minor component of m.w. 200,000. Examination of both tissue sections and isolated cells indicated that RGL-1 stained the majority of the lamina propria lymphocytes and IEL but only very few cells (less than 2%) in the lymphoid organs and small numbers of lymphocytes in other mucosae. In the small intestine, RGL-1 stained lymphocytes with the helper (W3/25) as well as the cytotoxic/suppressor (OX8) phenotype. The antibody reacted with 95% of the granular IEL but with less than 0.1% of the blood large granular lymphocytes. Although mature IgA plasma cells in the lamina propria were RGL-1-, some large IgA-containing cells were weakly positive. In the gut-associated lymphoid tissues (GALT), studies combining immunofluorescence and autoradiography indicated that 56 and 73% of rapidly dividing cells of mesenteric lymph nodes and of thoracic duct lymph (TDL) stained with RGL-1, respectively. In addition, 90 to 100% of the IgA-containing blasts of MLN and 75% of those of TDL were labeled by RGL-1. In contrast, rapidly dividing cells of spleen and of peripheral lymph nodes did not stain with RGL-1. Because RGL-1 can be demonstrated on both intestinal lymphocytes and their immediate precursors in the GALT, its expression may be related to the homing of lymphocytes into the gut mucosa.

Animals↗

[LAV infections and the acquired immunodeficiency syndrome in infants].

The clinical and immunologic abnormalities of 7 infants with Lymphadenopathy Associated Virus (LAV) infection are reported. Indicative immune changes, positive anti-LAV serologic test and/or virus isolation led to the diagnosis. In a case with a particularly severe form of the disease, whose mother died from AIDS, serologic tests and virus isolation were negative. Beside a case associated with blood transfusion, the familial and ethnic context helped the diagnosis. Clinical and biochemical features were close to those in adult AIDS, including hepatosplenomegaly, polyadenopathy, a decreased absolute number of OKT4(+) lymphocytes and hypergammaglobulinemia. The importance of cellular and sometimes also humoral immune deficiency was highly variable. For 4 patients, the severity of the immune deficiency allowed the diagnosis of AIDS. Occurrence of such an infection in the first months of life suggests a fetomaternal viral transmission; however, a postnatal contamination cannot be ruled out. Long-term prognosis is difficult to assess. It depends, among other factors, on the importance of the immune deficiency.

Acquired Immunodeficiency Syndrome↗

HLA-haploidentical bone marrow transplantation for severe combined immunodeficiency using E rosette fractionation and cyclosporine.

Eight patients with severe combined immunodeficiency received bone marrow cells from their HLA haplotype-identical fathers after bone marrow T cell depletion by rosetting with neuraminidase-treated sheep red cells. Because the method led to the infusion of a small percentage of T lymphocytes (0.1% to 0.3%), cyclosporin was given by continuous intravenous infusion for two months in order to prevent the occurrence of graft-v-host disease (GVHD). Three patients who did have residual nonfunctional T lymphocytes received busulfan and cyclophosphamide before transplantation. Engraftment was observed in seven patients, and severe GVHD was not seen. Two patients died early after the bone marrow transplantation because of prior infections, and a third died at day 90 from a B cell lymphoproliferative syndrome. The five other patients are doing well. Stable engraftment has been achieved with reconstitution of cell-mediated immunity in 5/5 and humoral immunity in 4/5 patients.

Adenosine Deaminase↗

[Bone marrow graft: graft versus host reaction and rejection].

The graft versus host reaction (GVH) remains the major setback of allogeneic bone marrow transplantation. GVH is observed in more than 50% of HLA identical transplantations. GVH can occur as an acute or chronic syndrome. The severity is variable, the GVH being responsible for the death of 10 to 20% of transplanted patients. Cytotoxic T lymphocytes or helper T lymphocytes are able on their own to mediate the GVH reaction. These T lymphocytes are specific for minor histocompatibility antigens. Some of them are restricted to specific tissues such as the skin. The frequency of the GVH reactions is increasing with the age of the recipient, with the degree of HLA antigens incompatibility and with presence of viral infections in the host. Several ways of GVH reaction prevention have been used such as the use of Methotrexate or Cyclosporin A. T cell depletion of the bone marrow appears to be the most effective method, allowing the achievement of HLA mismatched bone marrow transplantation. However, bone marrow T cell depletion is associated in 10 to 20% of cases with graft failure. The rate of graft failure is extremely high for HLA incompatible bone marrow transplantations. This could be due to the lack of antirejection effect of donor T lymphocytes. Graft rejection is mediated by host residual immunity. Cytotoxic T lymphocytes and perhaps natural killer cells are the effector cells. Several procedures attempting at the prevention of graft failure are currently under investigation. They tend to block the host residual immunity either by increasing chemotherapy or total irradiation, by using lymphoid irradiation or by the in vivo infusion of monoclonal antibodies specific for lymphoid cells.

Bone Marrow↗

[Chemotherapy and ovarian function. Retrospective analysis in 17 girls treated for malignant tumor or hematologic disease].

Ovarian function was investigated in 17 patients aged 13 5/12 to 30 years who had received various types of combined chemotherapy without any irradiation. Ovarian insufficiency was found in 6 cases with amenorrhea (n = 5) or irregular menstruations (n = 1). There is a high risk of sterility in these cases although as described in one case, a normal pregnancy occurred in spite of evidence of ovarian failure. Cyclophosphamide seemed to be less harmful when given before puberty. Great variations in individual susceptibility for relatively low doses were observed with this drug. The combination with other drugs in some protocols might play a role in these cases. At variance with results reported in adults, the MOPP chemotherapy used in children with Hodgkin's disease did not induce ovarian dysfunction.

Adolescent↗

Genotyping with DNA probes in combined immunodeficiency syndrome with defective expression of HLA.

We performed HLA genotyping by using restriction-enzyme fragments hybridized with specific HLA probes instead of traditional immunologic methods in two patients whose lymphocytes expressed so few HLA antigens on the cell surface that serologic methods failed. Segregation of restriction-fragment-length polymorphism permitted identification of the genotypes. In addition, known correlations between serologically determined antigens and restriction-fragment-length polymorphism were confirmed. We applied this approach in making therapeutic decisions regarding bone marrow transplantation.

Bone Marrow Transplantation↗