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Biomedical subjects

M Fellous

Publications and source records attributed to M Fellous.

At least 163 records · Page 9Linked to original sources
PubMed1982

A monoclonal antibody with anti-Burkitt lymphoma specificity. I. Analysis of human haematopoietic and lymphoid cell lines.

38-13 is a hybridoma-produced monoclonal rat IgM which appears to define a Burkitt's lymphoma-associated antigen (BLA). In this paper, we described the reactivity of 38-13 with a panel of human haematopoietic and lymphoid cell lines. In indirect immunofluorescence (IF) assays, 15 of 26 Burkitt's lymphoma (BL) lines studied were clearly stained with 38-13 (from 13 to 100% positive cells) by microscope, with varying numbers of heavily labelled cells. In these positive cell lines, fluorescence-activated cell-sorter (FACS) analysis demonstrated that BLA was actually present on all the cells. Positive BL included Epstein-Barr virus (EBV) genome-carrying lines and EBV-negative ones; thus, BLA is not related to the presence of EBV. Most of the 15 BL cells that reacted with 38-13 contained a typical t(8;14) translocation, but had variant translocations such as t(2;8) and t(8;22). The cells were derived from BL patients of different geographical origins and clinical features. Four BL lines were poorly stained and seven were negative with 38-13 in IF assays. The 32 EBV-positive lymphoblastoid cell-lines (LCL) studied were negative. In three line pairs, consisting of a tumor line and an LCL from the same patient, only the BL line was demonstrated to react with 38-13. A series of non-BL cells, including haematopoietic, lymphoid and solid tumor lines, all failed to react with 38-13. Various attempts to modulate the expression of BLA on BL cells were unsuccessful. However, it cannot be ruled out that BLA is actually a transient B-cell differentiation marker.

Animals↗
PubMed1982

A five-generation family with sacral agenesis and spina bifida: possible similarities with the mouse T-locus.

In man, a malformation that recalls some of the defects associated with T/t mutants in the mouse is sacral agenesis. We report on a family with a high incidence of sacral malformation, ranging from a complete absence of the sacrum (SA), with or without spina bifida aperta, to a spina bifida occulta (SBO) that could only be detected by x-ray. The condition appeared in a man with four children who were all affect, and thereafter, to varying degrees, in 17 of his 28 descendants. Segregation analysis has been performed in this family, using the Elston and Stewart transmission probability model [1971]. The two traits (SA and SBO) were first studied separated and then together. A fully penetrant major dominant gene is show to cause SA. When the phenotypes SA and SBO are considered together, Mendelian transmission is rejected. This could be explained genetically by two alternative hypotheses: genetic heterogeneity or a dominant major gene transmitted in excess by heterozygotes (tau Aa A = 0.896), suggesting a segregation distortion property of an allele at a T-like locus.

Adult↗
PubMed1982

Monoclonal antibodies as a tool for phylogenetic studies of major histocompatibility antigens and beta 2-microglobulin.

The cross-reactivity of several monoclonal antibodies recognizing monomorphic determinants of human HLA-A, B, C, and DR antigens and human beta 2-microglobulin (beta 2m) has been studied on peripheral blood leukocytes in 24 different species. An monoclonal HLA-A-, B-, and C-specific antibody and four monoclonal HLA-DR-specific antibodies cross-reacted with cells from all the primate species tested. Furthermore, antibodies HLA-DR-specific were positive with peripheral blood leukocytes (PBL) from cows, goats, sheep, horses, and dogs. Two monoclonal beta 2m-specific antibodies, which were positive with PBL from certain primates, also reacted with cells from cows, goats, sheep, horses, and dogs. Two other beta 2-m-specific antibodies reacted only with PBL from chimpanzees. No reaction could be detected with all our reagents in other classes tested (birds, reptiles, amphibians, and Teleostei).

Animals↗
PubMed1982

Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells.

In human cells treated with interferons, there is an increase in the amount of HLA-A,B,C and beta 2-microglobulin exposed on the cell surface. We have used a cloned HLA-A,B,C cDNA probe to demonstrate by molecular hybridization that this effect of interferon is preceded by a large increase in the amount of HLA mRNA in the cell. This effect was found in five different human cell lines, with purified leukocyte and fibroblast interferons. The increase in HLA mRNA is comparable in its kinetics and dose-response to the induction of (2'-5') oligo(A) synthetase mRNA by interferons. Therefore, interferons seem to activate at least two cellular genes which have different biochemical functions.

Cells, Cultured↗
PubMed1982

A new Epstein-Barr virus negative Burkitt's lymphoma derived cell-line. I. Analysis of cell surface markers and abnormal expression of HLA antigens.

CHEV, a new Epstein-Barr virus negative Burkitt's lymphoma derived cell line has been studied. Karyotype analyses demonstrated the t (8; 14) characteristic translocation. Cell surface characterisation of this line showed the presence of mu and chi immunoglobulin chains and beta 2-microglobulin and the absence of the complement receptor. We are unable to detect HLA--A, B alloantigens on the cell surface which was in contrast with an apparently normal expression of these antigens in the cytoplasm.

Antigens, Neoplasm↗
PubMed1982

Effects of H--Y antigen on morphologic and endocrine differentiation of gonads in mammals.

The effects of H--Y antigen, released in a soluble state by male human Burkitt lymphomas and mouse teratomas, were studied in the fetal gonads from 13 to 21-day-old rats and 98-day-old calves, using histologic techniques, radioimmunoassays for testosterone, and bioassays for Müllerian-inhibiting substance (MIS). Whereas no effect was detected in the younger gonads, some structural changes were observed in bovine and 21-day-old rat ovaries when cultured for 5 days with Daudi and male teratoma supernatants, but there was no synthesis of testosterone or MIS. These observations raise questions concerning the critical period of sensitivity to H--Y antigen of female gonads, and the dissociation between morphologic and biochemical events.

Animals↗
PubMed1981

Interferon enhances the amount of membrane-bound beta2-microglobulin and its release from human Burkitt cells.

Human leukocytes interferon (HuIFN-A) increased the amount of beta2-microglobulin on the surface of human Burkitt lymphoma cells (Ramos) and also increased the amount released into the culture medium. The effect was observed 1 h after addition of IFN. These results suggest that the increase in beta2-microglobulin on the cell surface of IFN-treated cells is not due to a decreased shedding of antigen from the cell surface, nor an "unmasking" of surface antigen, but rather to an increased synthesis of antigen.

Beta-Globulins↗
PubMed1981

Selective expression of blood group antigens on human teratocarcinoma cell lines.

The presence of the blood group antigens H, P, Pk as well as the T-antigen of Thomsen-Friedenreich (detected by the PNA lectin) was investigated at the surface of human embryonal carcinoma cells and of normal or tumor cell lines from adult individuals by an indirect immunofluorescence method. The PNA lectin binds to all the teratoma cell lines investigated but only occasionally to the adult cell lines. The H antigen was detected by fluorescence only onto the embryonic carcinoma cell PA1, but the H enzyme (2-alpha-L-fucosyltransferase) was found catalytically active in all teratoma cells tested: PA1, Susa, Tera I and Tera Ii. Finally, it was also shown that P and Pk antigens are expressed very early during development, prior to HLA and H or ABO.

ABO Blood-Group System↗
PubMed1981

Monoclonal antibody against a Burkitt lymphoma-associated antigen.

A monoclonal antibody, referred to as 38.13, was obtained by fusing murine myeloma cells with Lewis rat splenocytes sensitized with Daudi cells (human Burkitt lymphoma containing Epstein--Barr virus genome but lacking HLA-A, -B, and -C and beta 2-microglobulin molecules at the cell surface). 38.13 antibody was demonstrated to be a rat IgM. By complement-dependent microcytotoxicity and indirect immunofluorescence assays, 38.13 antibody was shown to react specifically with cells derived from Burkitt tumors, including both Epstein--Barr virus genome-carrying and Epstein--Barr virus-negative Burkitt lymphoma. By contrast, Epstein--Barr virus-containing lymphoblastoid cell lines derived from normal B lymphocytes were not recognized by 38.13 antibody. Fresh malignant cells from patients affected with various lymphoproliferative disorders were negative, except 4/8 having abdominal Burkitt-like lymphomas. Normal lymphocytes from peripheral blood, spleen, lymph node, tonsil, and bone marrow and mitogen (phytohemagglutinin, pokeweed mitogen, and concanavalin A)-activated blasts were also negative. Thus, 38.13 antibody apparently recognized a Burkitt-associated antigen that is not related to Epstein--Barr virus. The pattern of reactivity of 38.13 antibody with various Burkitt lymphoma cells appeared quite heterogenous and some Burkitt cells were consistently negative. 38.13 antibody thus defines a subset of Burkitt lymphomas.

Animals↗
PubMed1981

Characterization of human teratoma cell lines for their in vitro developmental properties and expression of embryonic and major histocompatibility locus-associated antigens.

Five human teratoma cell lines have been characterized for the presence of a certain number of marker antigens whose presence or absence has been shown to be characteristic of mouse embryonal carcinoma (EC) cells. Four out of the five lines have been shown to respond to at least some of the criteria associated with murine EC cells even though only limited in vitro differentiation could be demonstrated. The significance of certain unusual marker antigen combinations present on the cell line Tera I and its clones and so far unobserved for the murine model is discussed. The observation in Tera I populations of cells carrying simultaneously both the F9 and beta 2-microglobulin or HLA antigens, suggest that the human cell lines may represent a novel material for the study of mammalian differentiation.

Acid Phosphatase↗
PubMed1981

[H-Y antigen and sexual dysgenesis in man].

H-Y antigen is a surface component associated with the heterogametic sex of various species and supposed to induce testicular differentiation. Genes controlling directly or not the expression of H-Y antigen and testicular differentiation have been localized on Y as well as on X chromosome and even autosomal chromosome. However the genetical localization of the H-Y structural gene remains unknown. We analysed the expression of H-Y antigen in three types of sexual dysgenesis (males bearing XX caryotype, testicular feminization syndrome and one case of hermaphroditism) to clarify the function and the genetics of this antigen.

Androgen-Insensitivity Syndrome↗
PubMed1980

Characterization of a human ovarian teratocarcinoma-derived cell line.

A cell line (PA I), derived from human ovarian teratocarcinoma cells, was obtained by culturing ascitic fluid cells from a patient with recurrence of malignant ovarian teratoma. During early passages the cultured cells showed a variable morphology, a long doubling time, and a low plating efficiency (2%). After about 50 passages in vitro, a cell population which was more homogeneous and resembled embryonal carcinoma cells were obtained. These cells had a shorter doubling time (26 h), and increased plating efficiency (77%). The early-passage cells were aneuploid (P 24) whereas the late-passage cells had a normal diploid karyotype with one balanced translocation between chromosomes No. 15 and No. 20 (P 224). Details of the karyotype suggest that the cells are heterozygous, i.e. derived from a stage before the first meiotic division. One of the two X chromosomes were inactive, and the cells expressed HLA antigens (A28 and B12), and beta 2-microglobulin. Expression of F9 antigen, characteristic of two-cell and later preimplantation embryos, was absent, while expression of PCC4 antigen, expressed also by blastocysts, was present. This finding suggests that the line might express some embryonic characteristics. The PA I cell line maintained in monolayer cultures showed several characteristics of malignant cells. The proportion of malignant cells increased with successive passages in vitro. The late-passage cells represented a fairly homogenous population of malignant cells similar to embryonal carcinoma cells. Late-passage PA I cells, when seeded under conditions that prevented attachment of cells to the substratum, formed embryoid bodies consisting of an inner core of cells similar to embryonal carcinoma cells, surrounded by a rind of endoderm-like cells. These two cell layers were separated by a basement membrane-like structure containing fibronectin. The core embryonal carcinoma cells expressed high alkaline phosphatase activity whereas the endoderm-like cells had low alkaline phosphatase activity. Embryoid bodies seeded on an adhesive substratum formed polycystic structures divided by layers of epithelial-like cells and containing extracellular fibrils similar to collagen type I or III. In these cultures, further limited differentiation into endoderm-like, epithelial-like cells and pigmented cells was observed. Morphological differenciation of undifferentiated PA I cells into endoderm-like cells in monolayer cultures could be obtained by treatment with BrdUrd or by plating in low serum concentration and at low density. Cells with characteristic fibrillar distribution of fibronectin and actin microfilament bundles were then observed, indicating formation of cells lacking properties of malignant cells. As indicated by these results, the PA I cell line, in spite of a limited capacity to differentiate in vitro, shares some of the properties of mouse teratocarcinoma cell lines and might therefore serve as a useful model for studies on some developmental mechanisms in human cells.

Antigens, Surface↗
PubMed1980

Clinical, cytogenetical, histological, immunological and hormonal studies in a case of true hermaphroditism.

A true hermaphrodite with ambiguous genitalia and 46XX karyotype was studied from 18 months of age to 17 years. At 13 years, he developed an ambiguous puberty, with marked bilateral gynaecomastia and public hair score three. A relatively high testosterone level (21 nmol/l), not increased by hCG stimulation, was associated with a high LH level (6 UI/l). In the venous blood of the right ovotestis, the steroid concentrations were in the adult male range, especially testosterone (1400 nmol/l). After removal of the right gonad, large fluctuations of oestradiol levels were observed (150-810 pmol/l). The testosterone secretion of the left ovotestis was low, concentrations begin 4.2 and 130 nmol/l in peripheral and gonadal blood respectively at 16 years. A significant LH surge was induced by oral ethinyl-oestradiol before removal of the left gonad. The 5 alpha-reductase activity was normal in pubic skin. In the left gonad the concentrations of cytosol receptors for testosterone and 5 alpha-dihydrotestosterone (DHT) were significant: 14.5 and 65.5 fmol/mg protein respectively. However the plasma DHT level was not increased by hCG. Finally, the presence of H-Y antigen was demonstrated on lymphocytes. This accords with the presence of testicular tissue in an XX subject, and with significant testosterone production. The high testosterone production did not prevent the appearance of a positive oestrogen-LH feedback. The relative peripheral insensitivity to testosterone, is, in some ways, inconsistent with the presence of receptors for androgens.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1980

Reactivity of human lymphoid and lymphoblastoid cells with peanut agglutinin: detection of a blood cell subset which lacks detectable membrane HLA.

The number of cells reacting with fluorescein-labelled peanut agglutinin varies widely among human lymphoid organs. By separation techniques, reactive cells from tonsils were characterized as E-negative, non-immunoglobulin-bearing lymphocytes. In peripheral blood, the lectin reacted with a small percentage of lymphoid and monocytoid cells which lacked HLA membrane determinants but expressed the beta 2-microglobulin antigens. The latter phenotype was also found on human lymphoblastoid cell lines. Lectin binding thus provides an effective means of characterizing these cell subsets.

Antigen-Antibody Reactions↗
PubMed1980

Functional study and detection of HLA-D products on fractionated human bone marrow cells.

Bone marrow cells from nine normal human volunteers obtained from the Iliac crest, were used in this work for antigen determination and functional studies. The bone marrow aspirated cells were sequentially separated: elimination of erythrocyte, granulocytes and monocytes achieved by Ficoll-Isopaque centrifugation followed by plastic adherence. Purified bone marrow cells were finally separated by size using velocity sedimentation. The slow sedimenting small cells were shown to be mainly T lymphocytes, probably of blood origin. The medium sized bone marrow cells were shown to contain myeloid precursors (CFu-c). Large immature cells were in cycle actively synthesizing DNA molecules. HLA-D and HLA-DR detections on the fractionated cells were performed using three techniques: fluorescence with specific anti HLA-DR allo and xeno antisera; primed lymphocyte typing (PLT) with anti HLA-DR monospecific in vitro primed lymphocytes and detection of the HLA-D stimulating product using the bone marrow fractionated cells as stimulators in a mixed leukocyte culture. Concordant results were obtained with the three techniques. Lymphocytes in the bone marrow express HLA-D products a peripheral lymphocytes. Bone marrow fractions depleted of lymphocytes and monocytes also contain approximately 20% of cells expressing HLA-D products The meaning of the expression of HLA-D products on immature precursors non-lymphoid cells is discussed.

Bone Marrow Cells↗