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Biomedical subjects

B Genetet

Publications and source records attributed to B Genetet.

At least 91 records · Page 5Linked to original sources

Modulation of expression of mouse macrophage surface antigens by monoclonal antibodies.

Mouse macrophages from peritoneal cavity were exposed to monoclonal antibodies (MAbs) directed against cell surface antigens and the effect on antigen expression was investigated. The two Mabs used, 3A33 and 3A35, were produced by cell fusion between a mouse plasmacytoma and rat lymphocytes immunized against mouse macrophages. The binding of the MAbs to cell surface was measured by immunofluorescence and flow cytometry or by a radioimmunological technique. When injected i.p. the MAbs diminished the expression of the corresponding antigens but did not alter it when added to cultures of adherent macrophages. Antigenic modulation, however, could be produced in vitro either by inhibiting macrophage adherence during incubation with MAbs or by using a second antibody layer. MAb 3A33 (IgG2a) was more effective than 3A35 (IgM) in provoking modulation. The appearance of re-synthesized antigens on cell surface was not affected by macrophage adherence. The modulated antigens were found to internalize into cytoplasmic vacuoles.

Animals↗

Factor B (Bf) and glyoxalase genes in insulin-dependent diabetes mellitus.

The frequency distribution of alleles controlled by the factor B (Bf) and glyoxalase genes that are found close to the HLA system on chromosome 6 was studied in 170 insulin-dependent diabetic patients. The data were compared with those for HLA-A, -B and -DR antigens and were related to age of onset of diabetes. All the diabetics were ketosis prone and on permanent insulin therapy. A significant excess of BfF1 was seen in the diabetic patients (p less than 10(-4]. Glyoxalase frequency distribution showed no significant deviation from controls, whereas HLA-DR3 (p less than 10(-4] HLA-DR4 (p less than 10(-4] were increased. Breakdown of data by age of diagnosis of disease showed no increase in the frequency of BfF1 and GLO1-2 but an increase of HLA DR3 and DR4 in patients with early onset diabetes. The findings of the study are consistent with data reported by others investigators and support the notion that one or more genes mapping close to the HLA A. B and DR and to the Bf loci confer susceptibility to insulin dependent diabetes.

Alleles↗

Anti-HLA-A2 and -A28 monoclonal antibody: production and study of the cross-reaction.

An anti-HLA-A2 and -A28 monoclonal antibody, XV.17, has been prepared by immunizing a Balb/c mouse with PBL. This XV.17 monoclonal antibody is a cytotoxic IgM. Its reactivity was tested by lymphocytotoxicity test and indirect immunofluorescence technique, in parallel with an alloantiserum ORA having the same anti-HLA-A2, -A28 reactivity pattern, against different panels. Family studies were undertaken. Absorptions-elutions and cytofluorometry experiments were performed to study the cross-reaction. The XV.17 monoclonal antibody is cytotoxic against all the HLA-A2 and -A28 tested cells, and is absorbed by HLA-Aw23 and -Aw24 cell suspensions.

Animals↗

Filtration pressure and red blood cell deformability: evaluation of a new device: erythrometre.

The authors have tested a new device that records the filtration pressure of a suspension of red blood cells (R.B.C.) passing through a 3 micron pore diameter filter. As the flow rate is constant, the pressure increase allows to appreciate an index of the R.B.C. deformability. In order to test the performances of this new equipment, the authors have studied the influence of the variation of the following parameters. Haematocrit from 0.5 to 2%, Buffer composition; time elapsing from drawing to measurement: from hour 0 to hour 3. This analysis has been performed on donors; on packed red cells preserved in CPD, from D0 to D21 and on patients specimens and the results have been compared to the whole blood filtration according to the Reid and Dormandy method. The following parameters were simultaniously measured: Whole blood viscosity by means of a Low Shear 30 viscosimeter, Intraerythrocyte ATP by bioluminescence, Membrane lipid composition (cholesterol, phospholipids), Scanning electron microscopy. This new apparatus, measuring the filtration pressure seems to be a more sensitive and reproductible method allowing to approach the RBC deformability, and quite usefull in clinical haemorheology.

Erythrocytes↗

An anti-mouse macrophage monoclonal antibody reacting with T-derived leukaemic cells.

Hybridomas secreting anti-mouse macrophage antibodies were obtained by fusing a murine plasmacytoma with lymphocytes of a rat immunized against mouse macrophages. An IgM, monoclonal antibody (3 A 35) reacted with mouse monocytes, macrophages and polymorphonuclear leucocytes. It did not bind appreciably to erythrocytes, platelets and unstimulated T or B lymphocytes. However, 3 A 35 bound to various murine T-derived leukaemic cells and to a small proportion of Con A-stimulated thymocytes. Cross absorption experiments confirmed the existence of a common antigenic determinant on macrophages and leukaemic cells. The possibility that 3 A 35 identified a previously described antigen common to macrophages and normal or leukaemic T cells was investigated. The antibody was tested against thymocytes and macrophages of various mouse strains, some congenic for H-2 or T1a. The 3 A 35-detected antigen was found to be different from Ly5, Tla and Qa and did not represent a I-J encoded allotypic specificity.

Animals↗

[Complement markers Bf and C4 in multiple sclerosis].

Some immunogenetic HLA markers are significantly correlated with multiple sclerosis, e.g.: the antigens B7, DR2, and the associations B7-DR2, A3-B7-DR2. In addition, the polymorphism of the allotypes Bf and C4 is also controlled by chromosome 6; a study of these markers is therefore of interest. The study of Bf and C4 in multiple sclerosis included a population of genotyped unrelated patients: 50 patients for Bf markers and 41 for C4A and C4B markers. This study revealed an over-representation of allotype S and homozygous BfSS in multiple sclerosis. BfSS homozygote was significantly more frequent in the B7 negative and/or DR2 negative patients, i.e. when the risk markers per se were absent. No correlation could be evidenced with the remittent or progressive character of the disease. These data, obtained from the study of C4, are still preliminary ones. The results found with the Bf markers confirm the existence of a genetic factor in multiple sclerosis and suggest that the susceptibility gene of the disease could be closer to locus Bf than to locus DR.

Chromosomes, Human, 6-12 and X↗

[Relapse in Basedow's disease after treatment with synthetic antithyroid drugs. Prognostic value of analysis of the HLA system].

One hundred and eleven unselected patients with hyperthyroidism due to Graves' disease received decreasing doses of carbimazole for 18 months. Clinical examination and hormonal assays (serum T3, T4, free T4 index) were done at 4, 9 and 18 months of treatment. Patients were typed for 35 HLA antigens and were followed up for 2 years after withdrawal of treatment; 39 patients were excluded for various reasons and 72 were retained for study. Of the 72 patients, 37 relapsed and 35 remained in remission: 40 patients were DR3+ (20 relapsed) and 32 were DR3- (17 relapsed). HLA frequency was not significantly different in patients who relapsed and in those who remained in remission. Thus, under the conditions of this study, HLA frequency could not be used to predict relapse of hyperthyroidism due to Graves' disease. This study brings out an other interesting point: relapse frequency of about 50% focuses our attention on the limits of medical treatment.

Carbimazole↗

[Peripheral distribution of lymphocyte subpopulations in Basedow's disease. Decrease in suppressor T-lymphocytes].

The distribution of B- and T-lymphocyte subpopulations was studied in peripheral blood of 45 patients with untreated Graves' disease and 45 sex- and age-matched healthy controls. Blood samples were taken at the same hour in all subjects. The following tests were performed: HTLA and E (AET) for relative T-lymphocyte count, complement receptor (EAC) and surface immunoglobulins (IgS, IgG, IgM, IgA, kappa, lambda) for relative B-lymphocyte count. In 23 subjects of each group the subpopulations of T-lymphocytes were defined by their reactivity with monoclonal antibodies OKT8 (T-suppressor cells) and OKT4 (T-helper cells). Compared with the control group, patients with Graves' disease showed a decrease in the number of T-lymphocytes (HTLA: P less than 0.05: EAET: P less than 0.001) a decrease in T-suppressor cells (P less than 0.01), and no significant difference in B-lymphocytes and T-helper cells. Thus, the main lymphocyte characteristic in Graves' disease is a decrease in the relative value of T-cells, specifically affecting T-suppressor cells.

Adult↗

Characterization and sorting of mouse cytotoxic macrophages by their light scattering properties.

The light scattering properties of mouse activated macrophages were analyzed by flow cytometry. Peritoneal adherent cells from B. abortus treated animals were found to segregate into two subpopulations as a function of their forward angle and 90 degrees angle light scatter. The cell subpopulations were separated by automatic sorting. The strongly scattering ones contained an elevated proportion of large volume and acid phosphatase rich cells. Their nonspecific cytotoxic activity against tumor cells was more important than that of weakly light scattering cells. Thus, flow cytometry might be helpful to characterize and isolate cytotoxic macrophage populations.

Animals↗

[Enzymatic evaluation of blood donors].

Enzymatic, immunologic and hematologic dosages were performed in a group of blood donors. A significant part of this population showed anomalies in the enzymes, either isolated or associated and of variable importance. A systematic serological study of viral hepatitis A (VHA) and viral hepatitis B (VHB) was performed among these donors with biochemical anomalies. A more general biological study (immunology and hematology) completes this work.

Adolescent↗

An HLA-All association with the hemochromatosis allele?

Two hundred and seventy-four patients with hemochromatosis and 1005 controls were HLA-typed, and HLA haplotypes were determined for 163 patients and 123 controls. The increased frequency of antigen A3 and haplotypes A3, B7 and A3, B14 in patients with hemochromatosis was confirmed. After correction for the space taken up by A3, a significant increase in All was found. This increase could not be explained by cross reaction between A3 and All. All showed a phenotype association and a haplotype link with Bw35. The genetic significance of this increased All frequency is discussed.

Alleles↗

A prospective study of the relationship between relapse of hyperthyroid Graves' disease after antithyroid drugs and HLA haplotype.

One hundred and eleven unselected patients with hyperthyroidism due to Graves' disease received decreasing doses of carbimazole for 18 months. Clinical examination and hormonal assays (serum T3, T4, free T4 index) were done at 4, 9, and 18 months of treatment. Patients were typed for 35 HLA antigens and were followed for 2 yr after withdrawal of treatment; 39 patients were excluded for various reasons and 72 were retained for study. Of the 72 patients, 37 relapsed and 35 remained in remission; 40 patients were DR3+ (20 relapsed) and 32 were DR3- (17 relapsed). HLA frequency was not significantly different in patients who relapsed and those who remained in remission. Thus, under the conditions of this study, HLA frequency could not be used to predict relapse of hyperthyroidism due to Graves' disease.

Carbimazole↗

Properdin factor B (Bf) and glyoxalase in Graves' disease.

Patients with Graves' disease were phenotyped for properdin factor B (Bf) and glyoxalase, which are coded for by genes mapping close to the HLA region on the sixth chromosome. Frequency data were analysed in relation to HLA-A, -B and -DR typing data. Diagnosis of Graves' disease was based on the usual criteria including elevated T3 and T4 levels and free T4 index and a homogeneous thyroid scan. Ninety-four patients with Graves' disease were phenotyped for properdin factor B (Bf) and 37 for red cells glyoxalase (GLO). HLA-A, -B and -DR antigens were typed in 94 patients using a lymphocyte microcytotoxicity assay. The frequency distribution of Bf and GLO alleles showed no significant differences from control subjects. This finding contrasts with the reports of an increased frequency of BfF1 in insulin-dependent diabetes mellitus. The difference in the two diseases which are both associated with an increased frequency of the antigen combination D8-DR3, is accounted for by linkage disequilibrium between B18 and BfF1.

Chromosome Mapping↗

[Effect of interferon on cell populations enriched in NK activity].

We have studied the NK activity after either interferon action or not, in total lymphocyte populations, as well as in cellular populations enriched with NK activity. (LGL = 76 +/- 13%). The incubation with interferon lasts 16 hours at 37 degrees C. The result obtained is an increase of the NK activity of the total lymphocyte population, while the cellular population, formerly enriched with NK activity, is not affected. These results are in favour of a necessary cellular cooperation on the interferon action on NK cells.

Humans↗

[Relation between cyclic AMP and phagocytosis in human monocytes].

The involvement of cyclic adenosine 3'-5' monophosphate (cAMP) in the regulation of human monocyte phagocytosis of staphylococcus aureus in vitro was demonstrated by assay of adenylate cyclase (AC) and cAMP phosphodiesterase (PDE). Phagocytosis was associated with diminished AC activity (p less than 0,05) and concurrently increased PDE activity (p less than 0,005). Transmission electron microscopy provided evidence that these changes coincide with peak phagocytic activity occuring 10-20 minutes after the start of phagocytosis.

3',5'-Cyclic-AMP Phosphodiesterases↗