PubMed Health⌕ Search

Biomedical subjects

K Guy

Publications and source records attributed to K Guy.

At least 37 records · Page 2Linked to original sources
PubMed1986

Expression of MHC class II antigens in human B-cell leukaemia and non-Hodgkin's lymphoma.

In this review we have summarized our experiences of serological analysis of MHC class II antigen expression in human B cell malignant disease. Cells from a large number of cases of B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) have been examined for expression of class II antigens. Using a number of monoclonal antibodies which in some cases are specific for class II subregion products (DP, DQ and DR), MHC class II antigens were detected by indirect immunofluorescence and fluorescent activated cell sorter analysis in CLL and by immunohistochemical staining in NHL. At the cell surface in many cases of B cell malignant disease, products of the different class II subregion genes are non-coordinately expressed. The most commonly occurring pattern of non-coordinate expression of class II molecules is of expression of DP and DR antigens in the absence of detectable DQ expression. These findings are in contrast to normal B lymphocytes where DP, DQ and DR antigens are expressed together at the cell surface. There is considerable heterogeneity among cases comprising individual histopathological categories of B cell malignancy, and in many instances heterogeneous class II phenotypes are also found on cells from the same tumour. In chronic lymphocytic leukaemia, class II antigen expression is inducible in vitro by treating the cells with the phorbol ester TPA. CLL cells treated with TPA have much increased levels of class II antigen expression at the cell surface and much increased steady state levels of class II specific mRNA transcripts detectable with complementary DNA probes. Aberrant class II antigen expression may be involved in the pathogenesis of B cell malignant disease.

Antibodies, Monoclonal↗
PubMed1986

MHC class II antigen expression in normal human epidermis.

Monoclonal antibodies consistently demonstrated the presence of MHC class II antigens (HLA-DR,-DP and -DQ) on keratinocytes in normal human epidermis. Reactivity was normally greatest on the keratinocytes of the intraepidermal portion of sweat ducts or the external root sheath of hair follicles, but staining was noted on the surface of some interappendageal keratinocytes in most subjects. The patterns were varied but distinctive and depended on the antibody used. The functional importance of the MHC class II antigens expressed on normal keratinocytes remains to be investigated.

Aged↗
PubMed1986

MHC class II antigen and immunoglobulin expression in spontaneous phenotypic variants of the Burkitt's lymphoma cell line Namalwa.

Phenotypic variant sublines of the Burkitt's lymphoma cell line Namalwa were examined with cDNA probes for the different MHC class II beta chain genes and with monoclonal antibodies specific for the corresponding cell surface antigens (DP, DQ and DR antigens). Expression of MHC class II antigens in the Namalwa sublines (known as CSN/70, IPN/45, PNT and KN2) was compared with that of the B-lymphoblastoid cell line DEW1, which is identical to Namalwa in DR allotype (DR 2,4). There were markedly different levels of expression of MHC class II antigens among the cell lines: in DEW1 and the Namalwa KN2 subline DP, DQ and DR antigens were expressed on almost all the cells. On the PNT and IPN/45 sublines, DR antigens were expressed on all the cells, and DP and DQ antigens were expressed at detectable levels on only a proportion of cells. On CSN/70, there was weak expression of DR antigens on a minority of cells and no detectable expression of DP and DQ antigens. When examined with MHC class II-specific cDNAs, restriction fragment patterns of DNA were identical for all the cell lines, suggesting that they had structurally identical MHC class II genes. In the Namalwa cell lines the synthesis of Ig and the expression of MHC class II antigens were coordinately regulated.

Antibodies, Neoplasm↗
PubMed1986

Deficient expression of MHC class II antigens in some cases of human B cell leukaemia.

Cells from the peripheral blood of patients with B cell chronic lymphocytic leukaemia (B-CLL) and acute lymphoblastic leukaemia (ALL) were examined for the expression of MHC class II antigens, using a number of monoclonal antibodies (MoAb) including L243 (anti-DR) and TU22 (anti-DQ). There was wide variation in expression of MHC class II antigens in CLL, both from patient to patient and among cells from the same individual. In a number of subjects a significant proportion of the cells had detectable levels of expression of DR antigens but not of DQ antigens. In some cases of ALL although almost all cells were MHC class II positive, DQ expression was undetectable. Differentiation of CLL cells, induced by culturing the cells with 12-0-tetradecanoyl phorbol-13-acetate (TPA), was accompanied by increases in MHC class II expression at the cell surface of up to more than 20-fold, and resulted in detectable expression of DQ antigens on greater than 90% of the cells in all the subjects studied.

Antigens, Neoplasm↗
PubMed1986

Expression of MHC class II antigens in human B-cell leukaemia, and increased levels of class II antigens and DR-specific mRNA after stimulation with 12-O-tetradecanoyl phorbol-13-acetate.

Cells from the peripheral blood of B-cell chronic lymphocytic leukaemia (CLL) patients were examined serologically for the expression of cell surface MHC class II antigens with monoclonal antibodies (mAbs) specific for the products of HLA-DP, -DQ and -DR genes, and mRNAs from the cells of three patients were analysed with a cDNA probe specific for DR beta chain genes. In 12 cases of CLL studied by indirect immunofluorescence and FACS analysis, a variable proportion of cells failed to express detectable levels of HLA-DP and HLA-DQ antigens at the cell surface, although greater than 90% of the cells had detectable expression of HLA-DR antigens. In all cases, greater than 90% of the cells expressed MHC class I antigens and the majority of cells reacted with the Leu-1 (CD5) mAb. Cells from different patients expressed variable levels of MHC class II antigens, and this was reflected in the finding of variable levels of mRNA detectable with the cDNA probe. Culture of cells with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced much increased levels of expression of MHC class II antigens. HLA-DP and -DQ antigens were expressed on greater than 90% of the cells in all cases studied after culture of the cells with TPA, and MHC class II specific mRNA transcripts were correspondingly increased. In a single case of plasma cell leukaemia studied, MHC class II antigens were not detectable at the cell surface and their expression was not induced after culture of the cells with TPA.

Antibodies, Monoclonal↗
PubMed1985

Immunohistochemical analysis of human MHC class II antigens in B-cell non-Hodgkin's lymphomas.

Twenty cases of B-cell non-Hodgkin's lymphoma (NHL) were evaluated by immunohistochemical staining of frozen sections with a panel of anti MHC class II monoclonal antibodies (MCA). These studies showed marked differences in the expression of class II antigens both between different cases and within the population of cells of individual cases. In all of the cases studied the majority of the tumour cells reacted with MCAs directed against determinants common to the products of SB and DR loci. However, MCAs specific for DC determinants failed to react with 3/20 cases and in several other cases stained only a minority of cells. Absent or reduced expression of DC antigens was most marked in lymphocytic lymphoma; however, in centroblastic-centrocytic and centroblastic lymphomas, DC antigens could be detected on the majority of cells.

Antibodies, Monoclonal↗
PubMed1985

Activated T cells in Graves' disease before treatment.

The aim of this study was the definition of abnormalities occurring within T-cell subsets of thyrotoxic Graves' patients before treatment. Special emphasis was placed on the enumeration of activated T cells using a number of new monoclonal antibodies. Lymphocytes from 22 Graves' disease patients were examined. The total number, the percentage of 'helper/inducer' and 'suppressor/cytotoxic' positive cells were evaluated using the antibodies T3, T4 and UCHT4, whereas the cells with killer activity were defined by H25. Activated T cells were detected using the antibodies DA6.231, DA6.164, and L243 which bind different epitopes of the beta chains of class II surface antigens and 4F2, which binds a 120,000 molecular weight glycoprotein. The results show no significant change in the total T, helper or suppressor cell phenotype, but an increase in the killer cell percentage was noted. Of those patients tested, 19 of 22 showed an increase in activated T cells, 18 of 22 patients showed a significant increase of T cells bearing class II antigens, 11 of 22 showed an increase of T cells staining with another activated T cell antibody, 4F2. The anti-DR antibodies expressed different binding characteristics, the most striking difference being seen between the antibodies DA6.231 and L243. The results of this study suggest an heterogeneity of the immune response, or differences in activation stage in patients with Graves' disease before therapeutic intervention. An important role for these cells in the pathogenesis of this disorder can be inferred.

Adolescent↗
PubMed1984

T-cell proliferation and expression of MHC class II antigens.

Two monoclonal antibodies to major histocompatibility complex (MHC) class II antigens, which in combination identify beta chains encoded by the SB and DR loci, were used to investigate which of these gene products were expressed at the cell surface of unstimulated T cells and at various stages of mitogen-induced T-cell maturation. In tests on blood lymphocytes from healthy donors 12% of T cells expressed class II antigens, but only SB antigens were expressed. During activation of T lymphocytes, SB-coded antigens were expressed before DR antigens, and the kinetics of SB expression correlated with the proliferative response of T cells. These results and consideration of recent reports from other laboratories lead us to suggest that SB-coded class II antigens play a role in T-cell proliferation.

Cells, Cultured↗
PubMed1983

Enhanced expression of human Ia antigens by chronic lymphocytic leukemia cells following treatment with 12-O-tetradecanoylphorbol-13-acetate.

Using a panel of monoclonal antibodies which detect framework determinants of human-Ia alpha and beta polypeptides and the DC-specific monoclonal antibody Genox 353, the in vitro effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the expression of Ia antigens by cells from chronic lymphocytic leukemia (CLL) patients have been studied. In all subjects studied a great increase in expression of framework Ia determinants was found following culture of CLL cells for 90 h with TPA at 10(-7) g/ml. TPA treatment of CLL cells also induced increased expression of Genox 353+ antigens, in some cases where Genox 353 binding was either negligible or not detectable in cells cultured in the absence of TPA.

Antibodies, Monoclonal↗
PubMed1983

Monoclonal antibodies against HLA-DR antigens replace T helper cells in activation of B lymphocytes.

In the presence but not in the absence of pokeweed mitogen (PWM), monoclonal antibodies against HLA-DR antigens 147 and 164 helped highly purified B lymphocytes to proliferate and mature to Ig-secreting cells. In contrast, neither anti-DR antibody 231 nor the UCHT1 monoclonal anti-human T cell antibody (both of the same isotype as the 147 and 164 anti-DR antibodies) exhibited any helper activity on B cells. B cells pulsed with PWM and subsequently cultured in the presence of anti-DR antibody 147 or 164 proliferated and secreted Ig, whereas B cells that first were pulsed with antibody 147 or 164 and then incubated with PWM did not. PWM alone did not induce any of these responses on purified B cells. Also, antibodies 147 and 164 significantly increased the number of Ig-secreting cells obtained from the WT51 Epstein-Barr virus-transformed B-cell line. Anti-DR antibody 231 inhibited the helper activity on WT51 cells mediated by anti-DR antibody 164. Finally, anti-DR antibodies 147 and 164 assisted B cells from the spleen of athymic nu/nu mice (which bear I-E-encoded products) to produce IgM antibodies against sheep erythrocytes. However, these antibodies had no effect on mouse B cells which do not express on their surface I-E-encoded Ia antigens. Taken collectively, these findings suggest that the structures detected by anti-DR antibodies 147 and 164 on B lymphocytes function as acceptors/transducers of T-cell-derived helper signals.

Animals↗
PubMed1983

Biochemical variation of human Ia like antigens detected with monoclonal antibodies.

Four mouse monoclonal antibodies to human B cell surface determinants previously described as being directed against Ia like (MHC class II) antigens, have been shown to precipitate Ia alpha and beta chains. Electrophoretic transfer experiments showed one antibody to be directed against Ia alpha chains and two others to be against Ia beta chains. The antibodies were then used to analyse a range of cell types and a large number of lymphoblastoid and lymphoma cell lines. Ia antigens could not be detected on peripheral blood T cells, cord endothelium or T cell lines but their presence was confirmed on activated T cells and peripheral blood non-T cells. There was both qualitative and quantitative variation of Ia like antigen expression on B cell lines, including an apparent genetic polymorphism in alpha chain structure unrelated to DR allotypes and a single instance of a beta chain of abnormally high molecular weight.

Antibodies, Monoclonal↗
PubMed1983

Circulating immune complexes in diabetics: the influence of sex, age, duration of disease and type of treatment.

The influence of sex, age, duration of diabetes and type of antidiabetic treatment on soluble immune complexes levels was investigated in the sera of 276 randomly selected diabetics. Immune complexes were detected by the solid phase C1q binding test. The prevalence of immune complexes was significantly higher in insulin treated than in non-insulin treated diabetics. Within the insulin treated group, the prevalence in diabetics of 11-20 yr duration was significantly higher than in the remainder. No difference in immune complexes levels was found between males and females. The age of the patients did not have any correlation with the levels of immune complexes. These findings suggest that some of the immune complexes detected in randomly selected diabetics are related to insulin treatment, reflecting either differences in the type of diabetes or the effects of heterologous insulin.

Adolescent↗
PubMed1983

The correlation between insulin antibodies and circulating immune complexes in diabetics with and without microangiopathy.

The relationship between immune complexes and insulin antibodies was evaluated in 237 insulin treated subjects with a duration of diabetes of more than 1 year. Ninety-seven diabetics were selected at random (group 1) whereas 140 according to the presence of diabetic microangiopathy (group 2). Immune complexes were evaluated by the solid phase C1q binding test in all patients and by conglutinin radioimmune assay in most of them. Insulin antibodies were determined by Christiansen's and Anderson's methods. Immune complexes as detected by the solid phase C1q method were found increased in group 1 and there was an inverse correlation between these complexes and insulin antibody levels. In group 2 patients with microangiopathy the amount of this kind of complex was significantly greater than in those without microvascular lesions and there was no correlation with insulin antibodies. Immune complexes as detected by conglutinin were found increased in group 2 patients and these were significantly correlated with the level of insulin antibodies. No increase in these immune complexes was found in patients with microangiopathy when compared with patients without microangiopathy. Insulin antibodies were not correlated with the presence of complications. Overall, immune complexes detected by C1q binding were significantly correlated with the presence of microangiopathy. In patients with high insulin antibody levels the complexes formed were not detected by C1q binding. The immune complexes detected by conglutinin are correlated with insulin antibodies, but not with the presence of microangiopathy.

Adolescent↗
PubMed1983

Humoral immunity in type 1 diabetes mellitus: a prospective study.

Cytoplasmic islet cell antibodies, as detected by anti-IgG (ICAb), and circulating immune complexes (AgAb), detected by the solid phase C1q test (C1qSP), were evaluated in 153 insulin dependent diabetics (IDD) at diagnosis and subsequently in 88 of these patients who were studied prospectively at regular intervals for up to 3 yr. AgAb detected by the conglutinin (KgBt) and Raji cell (RAJI) techniques were also studied at diagnosis in 34 and 50 diabetics respectively. Normal controls were included in the AgAb studies. Complement fixing islet cell antibodies (CF-ICAb) were evaluated in 30 randomly selected diabetics both at diagnosis and after 6 months. Viral antibodies (VAb) were measured in 30 IDD at diagnosis and in 30 matched controls. Insulin antibodies (IBC) were measured 9 months after diagnosis in 35 diabetics and HLA studies (B8 and B15) performed in 115 patients. In the prospective study the ICAb positivity declined from 50% at diagnosis to 45, 38, 36, 31, 26, 19 and 17% at 1, 3, 6, 9, 12, 24 and 36 months after diagnosis respectively. CF-ICAb were found in 30% of the diabetics at diagnosis and in 23% at 6 months. All patients with CF-ICAb at diagnosis were ICAb positive whilst only 47% of patients with ICAb also had CF-ICAb in the serum. AgAb were found at diagnosis in 35% of patients by C1qSP (p less than 0.001 vs. normals), in 35% by KgBt (p less than 0.001) and in 54% by RAJI (p less than 0.002). Eighty-four patients were studied at diagnosis by more than one AgAb method and of these 57% had at least one positive AgAb result. AgAb by C1qSP declined to less than 20% within 6 months of diagnosis. AgAb, as measured by C1qSP and RAJI techniques, correlated with ICAb at diagnosis whereas there was no correlation with VAb levels, IBC values, nor with the HLA antigens. There was no correlation between AgAb (C1q) and CF-ICAb. HLA B15 positive patients tended to form higher IBC levels than B15 negative patients. Thus, AgAb presence seems to parallel that of ICAb in the early stages of diabetes and both phenomena may be primarily or secondarily involved in the development of the disease.

Adult↗