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B B Cohen

Publications and source records attributed to B B Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1992

Familial breast cancer.

Familial clustering of breast cancer has been recognised for over a century but until recently a genetic basis has been suspected rather than proven. Epidemiological studies have tended to support the view that an autosomal dominant gene, with high but incomplete penetrance, accounts for most breast cancer families. However, it is likely that several different predisposing genes are present within most populations. Difficulties arise in a conventional 'linkage mapping' approach to identifying these genes, first, because it is not clear that genetically homogeneous groups of families can be recognised on the basis, for example, of mean age of onset or pattern of other cancers within the kindred and, second, because breast cancer is so common (affecting almost one in twelve women) that large affected kindreds are likely to include an admixture of sporadic (non-genetic) cases. Cytogenetic and 'Loss of Heterozygosity' (LOH) studies in sporadic breast cancers have pointed to several candidate loci for breast cancer genes but there is no clear consensus from these two approaches that might direct attention to any prime target region. Recent reports of tight linkage between familial breast cancer (early onset) and breast/ovarian cancer (regardless of mean age of onset) and a locus on chromosome 17q21 defined by the anonymous probe CMM86, have not been confirmed in detail but have led to the identification of a locus some 15 Mb centromeric of CMM86 that gives a high positive lod at very low recombination fraction in fifteen Edinburgh breast and breast/ovarian cancer families. The disease in the majority of such families therefore appears to be attributable to a mutant gene at 17q12-21. A much smaller proportion of familial breast cancer is accounted for by mutations in the p53 gene (17p13). Not all such families fulfil the criteria for Li-Fraumeni syndrome and not all of the inherited mutations lie within exon 7 of p53. Counselling of members of breast cancer families becomes more exacting as these genetic lesions are identified. It is essential to extend the collection of data and tissue (blood or fixed pathology material) as widely as possible to confirm linkage to a specific locus within each individual kindred, to define the precise mutation and to establish the cancer phenotype and its penetrance. In the course of these studies a substantial population of women at high risk of breast (and other) cancer will be identified. Resources should be directed to this population so that optimum procedures for screening and prevention can be developed.

Breast Neoplasms↗
PubMed1991

Inequities in hospital care, the Massachusetts experience.

This study examined the relationship between patient insurance status and the process and outcome of hospital care in Massachusetts, a state that has had an uncompensated care pool for paying hospitals since 1986. This study examined data on 4,972 patients admitted to a Massachusetts hospital on an emergency basis in 1987 and diagnosed with acute myocardial infarction. We classified these patients into three groups: having fee-for-service insurance, having prepaid coverage through a health maintenance organization (HMO), or being uninsured at the time of hospital admission. Results showed treatment differences by insurance status and significantly greater mortality rates for uninsured patients than for either fee-for-service or HMO patients. Our findings indicate that in Massachusetts the process and outcome of hospital care do differ by insurance status.

Cardiology Service, Hospital↗
PubMed1990

Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis.

The DNA of paired tumour and blood leucocyte samples from a large series of breast cancer patients was analysed to map regions of loss of heterozygosity on chromosome 17. The high frequency of loss of heterozygosity on 17p was confirmed, and a third of informative tumours had also lost an allele at the long arm locus THH59. On the short arm two distinct regions of loss of heterozygosity were identified, in bands p13-3 and p13-1. The latter probably involves the structural gene p53, which has been implicated as an oncogene or as a tumour suppressor in various human cancers. 17p 13-3, however, showed a significantly higher frequency of loss of heterozygosity, and there was no correlation between allele losses at the two sites. Nevertheless, loss of heterozygosity at 17p 13-3 is associated with overexpression of p53 mRNA, suggesting the existence of a gene some 20 megabases telomeric of p53 that regulates its expression. Lesions of this regulatory gene seem to be involved in the majority of breast cancers.

Alleles↗
PubMed1990

Production and regulation of interleukin 6 in human B lymphoid cells.

Human B cell lines were screened for production of interleukin 6 (IL 6) by the B9 hybridoma cell bioassay. Some long-established lines such as RPMI 1788, CESS and recently established early-passage Epstein-Barr virus (EBV)-transformed lymphoblastoid lines were constitutive IL 6 producers. Other long-established lymphoblastoid lines such as RPMI 8866 and SKW6.4 and all Burkitt lymphoma lines tested were nonproducers of IL 6. Constitutive production of IL 6 in early passage lines could be enhanced by the phorbol ester phorbol 12-myristate 13-acetate (PMA) and recombinant (r)IL 4 but not by rIL 1 alpha or rIL 1 beta. Nonproducing EBV-transformed lymphoblastoid cell lines could be induced to IL 6 production by PMA, rIL 1 alpha, IL 1 beta and IL 4. Among the nonproducing lines SKW6.4 was induced to IL 6 production by PMA, rIL 1 alpha, rIL 1 beta and rIL 4, whereas RPMI 8866 was induced only by PMA, to a limited extent by rIL 1 alpha and rIL 1 beta but not at all by rIL 4. There was no induction of IL 6 by any recombinant cytokine in the two Burkitt lymphoma lines but measurable production of IL 6 was induced by PMA in one of them (EB4). Cytokines which were neither enhancers nor inducers of cell lines on their own included rIL 2, rIL 5, interferon (rIFN)-gamma, native purified IFN-alpha, tumor necrosis factor (rTNF)-alpha, rTNF-beta and purified platelet-derived transforming growth factor-beta. rIL 4 synergized with either rIL 1 alpha or rIL 1 beta in the induction of IL 6 in the nonproducing line SKW6.4. Similar effects were also seen in this line with combinations of (a) rIFN-gamma and rIL 4 and (b) IFN-alpha and both rIL 1 alpha and rIL 1 beta. rIL 4, with or without rIL 1, was more effective than rIL 6 in the induction of IgM synthesis in SKW6.4 and the effect was only partially inhibited by anti-IL 6 antiserum at a dose which totally inhibited IL 6-induced IgM production. Normal peripheral blood lymphocyte populations pre-activated by anti-immunoglobulin rosetting exhibited enhanced production of IL 6 in the presence of rIL 4 and PMA but not in the presence of rIL 1, in contrast to the behavior of adherent mononuclear blood cells which showed IL 4-induced down-regulation of IL 6 production.(ABSTRACT TRUNCATED AT 400 WORDS)

B-Lymphocytes↗
PubMed1989

mAb KUL/05 identifies a denaturation-resistant determinant shared by class II MHC products DR, DQ and DP.

mAb KUL/05, a novel murine monoclonal antibody, reacts with molecules displaying the typical tissue distribution and molecular profile of class II MHC antigens. An extensive scrutiny employing serological and immunochemical assays on DR homozygous and DR alpha- mutant cell lines has shown that this reagent displays some additional, interesting features, namely mAb KUL/05 (a) binds in a broadly monomorphic fashion to cells of DR1 through seven specificities, (b) recognizes a determinant shared by a large proportion of DR, DQ and DP beta chains from most haplotypes, in both their monomeric and alpha chain-associated forms, and (c) reacts with frozen, acetone-fixed, as well as conventional, formalin-fixed, paraffin embedded tissues. Thus, mAb KUL/05 is likely to represent a useful adjunct for the study of the expression of class II MHC products in normal and pathological tissue specimens.

Animals↗
PubMed1988

A reliable method for the analysis of human MHC class II alpha and beta chains by Western blotting of IEF gels.

The solubility and ensuing transfer problems associated with IEF separation and blotting of membrane proteins have been eliminated by confining NP40 to the sample region of the gel and replacing it with octylglycoside in the separating gel. This permitted excellent separation of both the alpha and beta chains of the human MHC antigens and their subsequent detection by Western blotting.

Detergents↗
PubMed1988

A human lymphoblastoid B line with an abnormally large MHC class II beta chain.

We have examined the MHC class II beta chains in lymphoblastoid cell lines from over 200 individuals and describe one line which possesses, in addition to normal beta chains, a species of beta chain of unusually high Mr and abnormal pI which appears to be a product of the DR locus. This abnormality in Mr, detected by SDS-gel electrophoresis, was apparent only in the presence of mercaptoethanol and was shown to be due to difference in polypeptide chain length rather than to extra glycosylation.

B-Lymphocytes↗
PubMed1987

A new set of monoclonal antibodies to human MHC class II alpha chains demonstrates that most alpha epitopes are inaccessible on the living cell surface.

When mice were immunized with a mixture of human MHC class II alpha and beta glycoprotein chains, the predominant antibody response was anti-alpha, and from a subsequent fusion experiment over 60 hybridomas showing anti-alpha activity were generated, compared with 11 anti-beta secretors. These findings contrast with the relative paucity of anti-alpha monoclonals described previously. Use of a miniaturized Western blot screening protocol was a critical factor in the present study since the anti-alpha monoclonals do not bind to the surface of living B cells and would therefore be missed in conventional screening assays. After glutaraldehyde fixation of target B lymphocytes or B-cell lines, the majority of anti-alpha monoclonals do react in a radio-immunobinding assay, although none binds as strongly as pan-reactive anti-beta chain antibodies. This suggests that the immunogenic epitopes of alpha chains are normally concealed by the three-dimensional folding of the alpha beta dimer. The anti-alpha monoclonals were all monomorphic but varied in the extent of their reactivity with alpha chains separated on one-dimensional and two-dimensional IEF gels. The most reactive antibodies identified up to seven distinct components among mature class II antigens from solubilized cell membranes.

Animals↗
PubMed1984

A mild procedure for separating polypeptide chains prior to immunoprecipitation and western blotting analysis.

Conventional cleavage of linked polypeptide chains by heating in SDS can so alter molecular structure as to interfere with antibody binding, on which both immunoprecipitation and 'western blotting' depend. As an alternative, gentle treatment with acid at room temperature or at 0 degrees C was effective in separating the alpha and beta chains of human MHC Class II glycoprotein dimers and proved superior in terms of preservation of at least one labile epitope on the beta chain.

Antigen-Antibody Reactions↗
PubMed1984

The use of detergents in velocity sedimentation of cell culture IgM.

The biosynthetically radiolabelled secreted proteins of human lymphoblastoid cell lines have been analysed by sucrose gradient velocity sedimentation. The addition of detergent to the gradient buffer dramatically improves the recovery of immunoglobulins from cell line supernatants, allowing the gradient fractions to be analysed further both serologically and biochemically. The results of these analyses show that IgM is synthesised in the 19S form and can be clearly separated from other components which include free light chains. Immunoglobulin appears to form a much larger portion of the proteins secreted by human lymphoblastoid lines than has formerly been recognised, a finding which may be of practical importance for the development and exploitation of human monoclonal antibodies.

Carbon Radioisotopes↗
PubMed1984

Correlation between tumorigenicity and altered glycosylation of a "leukocyte common" antigen in human lymphoid cell lines.

Five human lymphoblastoid cell lines which have become tumorigenic, as judged by transplantability into immunosuppressed mice, have been compared with earlier, non-tumorigenic stocks of the same cultures, recovered from liquid nitrogen. Analysis of the cell surface glycoproteins by SDS-PAGE, electro-transfer to cellulose nitrate and "blotting" with radioiodinated lectins, reveals an increase in the molecular weight of one band from around 190 kd to 220 kd, in each case coinciding with the acquisition of the tumorigenic phenotype. Probing the electrotransfers with a monoclonal antibody demonstrates that the altered glycoprotein is a member of the "leukocyte common antigen" family. The increase in molecular weight is due to the addition of carbohydrate residues which are removed by treatment with neuraminidase and endoglycosidase. Screening a larger number of lymphoid cell lines, including those derived from Burkitt's lymphoma, shows an excellent correlation between tumorigenicity and altered molecular weight of a leukocyte common antigen.

Animals↗