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Biomedical subjects

B Genetet

Publications and source records attributed to B Genetet.

At least 73 records · Page 4Linked to original sources

Murine monoclonal antibody suitable for use as an Rh reagent, anti-e.

The production by the hybridoma technique of a monoclonal antibody which behaves as an anti-e agglutinin is described. A reagent was made from ascitic fluid diluted in RPMI 1640 culture medium and bovine serum albumin. All red blood cells bearing the e antigen were agglutinated; no reactivity was recorded with untreated EE red cells suspensions. However, cross-reactivity was observed with enzyme-pretreated EE cells. The characteristics of this monoclonal antibody are described and are in accordance with the standard references.

Animals↗

[Anomalies of cellular immunity in Graves' disease treated by synthetic antithyroid drugs: effects on prognosis].

The involvement of humoral immunity mechanism in etiology of Graves' disease was observed for the first time in 1956. Twenty years later cellular auto-immune dysfunction was also described. To day, there is evidence for suppressor T cell deficiency and decrease in T suppressor lymphocytes in Graves' disease and cell mediated immunity might be one of the most important point in the pathogenesis of Graves disease. For the future, cellular auto-immune dysfunction might be used to predict the evolution of the disease and to choice the best therapeutic scheme.

Antithyroid Agents↗

[T lymphocyte subsets in alveolar lavage and peripheral blood in sarcoidosis and extrinsic allergic alveolitis].

Accumulation of inflammatory and immune cells within lung parenchyma would constitute the initial step in producing the alveolar structural abnormalities. It is usually assumed that alveolitis, as assessed by broncho-alveolar lavage (BAL), represents a biological assessment of lung disease activity. The aim of this study, using monoclonal antibodies, is to characterize the T lymphocytes alveolitis in the lung and in peripheral blood in 3 well-defined populations: 1 degree) control subjects (n = 7); 2 degrees) patients with biopsy proven mediastino-pulmonary sarcoidosis (sarc) (n = 73), classified according to their clinical activity as active, inactive, chronic, and treated; 3 degrees) patients with extrinsic alveolar alveolitis (EAA) (n = 19). For the same BAL volume, the % of CD4+ cells and the CD4/CD8 ratio are increased in chronic and active sarc, contrasting with an increase in the % of CD8+ cells and a decrease in the CD4/CD8 ratio in the EAA. In absolute values, there are 2 times as many CD4+ cells and 5 times as many CD8+ cells in EAA than in sarcoidosis. In sarcoidosis, corticotherapy tends to normalize the CD4/CD8 ratio although the intensity of the lymphocytic alveolitis is not affected. In the peripheral blood, lymphopenia is observed only in the active form of sarc. in the CD4+ population, without any significant change in the CD4/CD8 ratio compared to the other groups. The number and distributions of BAL. T lymphocytes subsets may constitute a biological indicator for diagnostic orientation, but they do not distinguish sufficiently between the different groups of sarcoidosis to be of any prognostic value.

Adult↗

[Immunologic characteristics of repeated spontaneous abortions].

In 28 couples with spontaneous abortions, data of immunological investigations revealed an elevated frequency of HLA DR compatibility and immunological characteristics defining distinct patterns of immune responsiveness. In the half of women with recurrent spontaneous abortion (RSA) we observed a failure to develop a recognition response to paternal inherited fetal antigens expressed by the lack of classical evidence of in vivo allo-immunization such as antipaternal antibodies, and the absence of the inhibitors of cell-mediated immunity found in maternal blood during pregnancy. In few cases, the paternal cells are inefficient to elicit in vitro maternal cell-mediated lympholysis. In most women with a normal pregnancy occurring after spontaneous abortions or prior to RSA, an immune recognition response was evidenced by the presence of antipaternal antibodies and/or blocking factor acting on in vitro cell-mediated lympholysis. These observations support the hypothesis that immunological process could be the cause of some fetal losses of unknown etiology, through a defective or unsuitable maternal immune response.

Abortion, Habitual↗

[Demonstration of new class I antigens in man].

The hypothesis of new class I antigens has been postulated in man, and several antigen systems have been proposed: HT (Gazit), TC (TCA, TCB) (Van Leeuwen). The present study describes a new class I antigenic marker system, expressed selectively on PHA-activated T lymphocytes and on lymphoblastoid B cell lines. These markers correlated at the cellular activation stage, have been called: human activation or HA markers. 7% of the sera from multiparous women present anti-HA antibodies. The definition of class I molecule (dimer 41K - 12K) has been established by a structural analysis of the molecule; the responsible gene, located on the 6th chromosome could be close to the HLA-A gene. The equivalence with the mouse Qa markers is postulated, but remains to be totally demonstrated.

B-Lymphocytes↗

[Anti-CD3 monoclonal antibodies. Characterization and function].

Four anti-T lymphocyte monoclonal antibodies were produced by the hybridoma technique. Percentages of miscellaneous labelled cell suspensions, as profiles of fluorescent histograms, showed a reactivity of these 4 reagents quite comparable to that observed with anti-CD3 monoclonal antibodies. Labelling summation studies, cell-sorting studies and blocking experiments gave similar results as gave other anti-CD3 reagents. Biochemical study and functional tests: modulation effects and mitogenic properties, argued for the belonging of these 4 antibodies to the CD3 cluster. The actual data concerning the CD3 molecule are briefly resumed to underline the interest of such antibodies in the understanding of T-lymphocyte activation mechanisms during the immune response.

Animals↗

[Chemiluminescence of phagocytic cells in chronic gingivitis and adult periodontitis].

Measurement of chemiluminescence (CL) produced by phagocytic cells spontaneously or upon stimulation by phorbol myristate acetate (PMA) was performed in patients with gingivitis and adult periodontitis, and in control healthy subjects. The study was performed simultaneously on phagocytic cells obtained from peripheral blood and from gingival blood, and on crevicular leukocytes. An elevated CL production was obtained in quiescent and PMA-stimulated phagocytic cells from peripheral blood in patients with gingivitis or periodontitis compared to non-diseased controls. Chemiluminescence produced by unstimulated crevicular phagocytes was similar to that of peripheral blood phagocytes in normal subjects, but it was decreased in periodontitis. Upon PMA stimulation, the CL response of crevicular phagocytes remained low in the three groups of subjects.

Adult↗

[Hemorheological disorders linked to alcoholism].

Haemorheological parameters were studied in 138 alcoholic subjects at different stages of the liver disease, compared to non alcoholic liver diseases and controls. Results showed 1) a decrease in whole blood filterability in the three groups of alcoholic patients associated with a decrease in erythrocyte ATP level, 2) an increase in blood and plasma viscosities, 3) morphological alterations visualized by scanning electron microscopy. These disturbances are correlated to the abnormalities of red cell membrane lipids composition: increase in cholesterol/phospholipids ratio, increase in saturated fatty acids and decrease in polyunsaturated fatty acids (arachidonic and linoleic acids). The responsibility of alcohol itself, in the genesis of these disturbances has been demonstrated by acute alcohol drinking experiments in healthy subjects.

Adenosine Triphosphate↗

[Value of computer processing of data acquired by cytofluorometry for biological analyses].

The amount of informations relative to cell analysis generated on a flow cytometer must often be processed on a computer so that accurate and efficient analysis can be performed on the stored data, and have the power to consider complex signal distributions. A Ortho 50H flow cytometer was complemented with a Persona 1600 microcomputer (LogAbax) via an acquisition system directly connected to the photomultiplier assemblies. In the configuration we used, three primary signals are processed and stored simultaneously, thus providing six parameters for each cell. The analysis of the data can be delayed or operated immediately after each acquisition. Turbo Pascal was used for all programming. The implanted programs are available for the processing of histograms relative to immunofluorescence or DNA analyses. They allow the user to operate on data obtained after selecting the cells on a two-parameter basis. Examples of immunofluorescence and DNA analyses obtained on experimental preparations are presented.

Animals↗

Multiple myeloma in two brothers. An immunochemical and immunogenetic familial study.

When multiple myeloma was diagnosed within 6 months in two brothers a family study was carried out in 34 relatives to assess the genetic factors involved. The monoclonal immunoglobulin isotype identified was identical for the two brothers (IgG kappa) as well as their genotype (a = A2B12BfSDR4 GIo2/d:A9B27BfSDR2GIol). Blood protein electrophoresis and the major histocompatibility complex markers (HLA A, B, DR, Bf, glyoxalase phenotypes) were also determined in the other family members. The immunochemical study revealed no other case of monoclonal gammapathy, but 12 cases of low gamma-globulin and three cases of polyclonal hypergammapathy were found. The immunogenetic study showed that no other family member had the a/d genotype of the two brothers, whereas nine family members were semi-identical for haplotype a and five for haplotype d. It is unlikely that a double immunochemical and immunogenetic identity in two siblings with multiple myeloma would be due only to random encounter, rather this finding suggests that, besides environmental factors, genetic factors may be involved in the pathogenesis. Systematic immunochemical and immunogenetic studies in familial multiple myeloma are proposed as a method to further elucidate an eventual genetic background in multiple myeloma.

Agammaglobulinemia↗

New class I in man: serological and molecular characterization.

New class I antigens in linkage disequilibrium with HLA-A antigen are demonstrated in PHA T and EBV preferential target cells using human alloantisera. These new antigens are defined as class I antigens by immunoprecipitation of a 41-12 k dimer. The molecule is shown to be distinct from the HLA-A, -B, -C molecule and in particular from the A3 molecule as in sequential immunoprecipitations, the depletion of the HLA-A, -B, -C molecule or A3 molecule (44-12 k) has no effect on the new molecule (41-12 k). Being present on the PHA T cells and lymphoblast lines, these antigens are considered as new epitopes involved in the the cell activation process.

B-Lymphocytes↗

A monoclonal antibody (3A33) that reacts with a mouse-specific epitope of Mac-1 antigen.

The 3A33 monoclonal antibody, obtained by fusing rat immune lymphocytes with mouse plasmacytoma cells, was directed against mouse macrophages. Antibody 3A33, a rat IgG2a, reacted with macrophages from all the mouse strains tested, with mouse blood monocytes and with 56% of bone marrow cells, but not with T lymphocytes. It immunoprecipitated an antigen with alpha and beta subunits, found to be identical to Mac-1 antigen after cross-absorption experiments with M1/70 monoclonal antibody. The two antigenic determinants of the Mac-1 molecule identified by the 3A33 and M1/70 antibodies both displayed reduced expression on inflammatory macrophages and comparable resistance to trypsin digestion. The sites of the determinants on this molecule seemed close together judging from the ability of both the 3A33 and M1/70 antibodies to block C3bi receptor sites and compete for cell binding. However, unlike antibody M1/70, 3A33 never reacted with human cells bearing Mac-1 antigen. Therefore, two closely related epitopes of the Mac-1 molecule - one specific for mouse and one common to mouse and man, were recognized by these monoclonal antibodies.

Animals↗

Applications of flow cytometry to the structural and functional study of immune responsive cells.

Although flow cytometry is not yet widely used for diagnostic purposes, it provides a powerful tool for investigating structural and functional properties of immune-responsive cells. By far, the largest application of immunofluorescence is in identifying specific cell surface features thereby allowing the discrimination of lymphocyte subpopulations (phenotyping normal and malignant cells), for analysing complex receptors on neutrophils and monocytes, for detecting the appearance of new surface antigens induced by cell differentiation or activation. Besides this, the technique sets objective standards for appreciating cell activation (changes in RNA content, increased phagocytosis, DNA synthesis, changes in membrane fluidity, pH gradient changes). Computer processing of measurements allows rapid accurate studies of several properties simultaneously.

Antigens, Surface↗

[Idiopathic hemochromatosis. Immunogenetics and diagnosis. Prevention by HLA genotypes].

Idiopathic hemochromatosis is an hereditary iron overload. The study of HLA types demonstrated clearly the linkage with HLA system. The preferential correlation established with A3 (72%) but other alleles were linked: B7, B14. HLA alleles were only the markers of hemochromatosis allele (H) and were not implicated in other iron overload. Family studied, defined two linked haplotypes: A3, Cw7, B7, Bw6, BfS, DR2, GLO1 et A3, Cw8, B14, Cw6, BfF, DRw6, GLO2. Demonstration of the recessive mode of inheritance was established by family studies. The affected siblings had the same HLA haplotype that the proband and homozygous or heterozygous expressed state was assessed in siblings. The HLA family types allowed to detect in 147 families 88 potential diseased patients among of them 73% had early blood-drawing.

Alleles↗

Diminution of circulating polymorphonuclear leucocytes by administration of a monoclonal antibody reacting with granulocytes and monocytes.

The monoclonal antibody 3A35 which binds mouse polymorphonuclear leucocytes (PMN) and monocytes was injected intravenously (i.v.) into normal mice. A great diminution of circulating PMN was observed. The percentage of PMN passed through a minimum (2.5%) 20 min after antibody injection and returned to normal value (18.3%) within 24 h. After repeated daily injections, the ability of the antibody to induce granulopenia attenuated. Moreover, mice bearing the 3A35-producing hybridoma as an ascitic tumor had a normal percentage of blood PMN and a normal granulopoiesis as judged from bone marrow cytological examination. Thus, the monoclonal antibody produced a transitory diminution of PMN but could not induce a lasting granulopenia.

Animals↗

Spleen cell populations in normal and tumor-bearing hamsters.

Spleen cell subpopulations from normal and tumor-bearing hamsters (TBH) were quantified using Petri dishes coated with specific antibodies, and by flow cytometric immunofluorescence analysis. The relative numbers of T cells (Thy + cells) decreased, by both methods, as a function of tumor growth, while the number of B cells (bearing surface Ig) increased. Cells without T or B markers (null cells) were more numerous in the spleen of TBH and a large number of them expressed the receptor for the Fc fragment of IgG. Splenic cells were also sorted according to their light-scattering properties, and electron microscopic analysis was performed on the sorted fractions. It showed the presence of secreting plasmocytes and activated macrophages in the spleen of TBH.

Animals↗