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Biomedical subjects

L Mayer

Publications and source records attributed to L Mayer.

At least 19 recordsLinked to original sources
PubMed1992

Morbidity in retired coke oven plant workers.

The effect of past occupational exposure on morbidity was studied in 354 coke oven workers in Lorraine Collieries (France) who retired between 1963 and 1982, and were still alive in 1988; 96% of them participated in this study. Occupational exposure to respiratory hazards during the working life was retraced for each subject. No significant association between the occupational exposure and the frequency of ischemic cardiopathies, arterial hypertension, gastro-duodenal ulcers, and respiratory symptoms was revealed. However, subjects who had worked on the Ovens, in the Workshops, and in the Byproducts showed a prevalence of arterial hypertension significantly higher than the non- or slightly exposed subjects. The healthy worker effect phenomenon, the exclusion of deceased subjects, and the small size of this retiree population may conceal possible differences between exposure groups.

Age Factors↗
PubMed1992

Persistent infection of human adenovirus type 5 in human monocyte cell lines.

Adenovirus infection of human monocyte hybridoma cell lines and the fusion partner U937 was investigated. Adenovirus adsorbed poorly to these cells as well as primary human alveolar macrophages. The virus-binding experiments showed a 100-fold reduction in apparent viral binding to these cells compared to the permissive HeLa cells. Adsorption of adenovirus to these cells could be enhanced by preincubation of adenovirus with its antiserum. Following entry into the cells amplification of adenovirus DNA was detected starting at 2 days postinfection but few mature virus particles were produced. The infected cultures survived the infection and continued to grow for more than a year. In these chronically infected cultures, linear adenovirus DNA persisted up to 200 copies per cell and a small amount of mature virus was produced. Infectious center assay and cell cloning experiments showed that the majority of the cells in the chronically infected cultures harbor adenovirus genome. These results indicate that restriction of replication of human adenovirus type 5 at the late phase results in persistent infection of U937 and the human monocyte hybridoma cell lines.

Adenoviruses, Human↗
PubMed1992

Restoration of immunoglobulin secretion in vitro in common variable immunodeficiency by in vivo treatment with polyethylene glycol-conjugated human recombinant interleukin-2.

Patients with common variable immunodeficiency (CVI) have decreased immunoglobulin levels resulting in frequent infections. Although previous studies have suggested that the B cell is intrinsically defective, numerous T cell deficiencies, including reduced interleukin-2 (IL-2) production, have been described. Since the addition of T cell cytokines to CVI B cells can increase Ig secretion in vitro, hypogammaglobulinemia in CVI may be due to defective T cell functions. To assess this possibility directly, we treated five CVI patients intravenously with a new biologic, human recombinant IL-2 conjugated to polyethylene glycol. Doses were 250,000 IU/m2 weekly for Weeks 1-4, 500,000 IU/m2 for Weeks 5-8, and 10(6) IU/m2 for Weeks 9-12. During and after treatment, B cells of all patients secreted 10- to 1000-fold more Ig in vitro. There was also a striking improvement in T cell helper activity since T cells of treated patients could induce 10- to 10,000-fold increases in Ig secretion by B cells from normal donors. No increase was seen in serum Igs during the study, but the anti-tetanus antibody of the IgG isotype could be detected in cell culture supernatants. Whether the effects of infused polyethylene glycol IL-2 are mediated through T or B cells, or both, is still unknown. However, these data reinforce the concept that CVI B cells may be competent, but, lacking essential T cell growth factors, in vivo maturation to Ig production does not occur.

Adult↗
PubMed1992

Inhibition of HIV-1 productive infection in hepatoblastoma HepG2 cells by recombinant tumor necrosis factor-alpha.

OBJECTIVE: To evaluate the role of liver cells in and the effect of tumor necrosis factor-alpha (TNF-alpha) on HIV-1 replication. METHODS: Human hepatoblastoma HepG2 cells were infected with various strains of HIV-1 and the effect of TNF-alpha treatment, either before or after infection, was monitored by p24 antigen assays. Northern blot analysis and gel retardation assays were performed to determine the expression of CD4 and HIV-1 trans-acting region (TAR)-binding proteins in these cells, respectively. RESULTS: HepG2 cells are CD4+ and support active HIV-1 replication, producing infectious virions, as measured by both p24 production and ability to infect T-cell lines with the virus produced by HepG2 cells. In contrast to the stimulatory effect of TNF-alpha on HIV-1 replication in T-cells and monocytes, up to 200 U/ml TNF-alpha treatment, at various times, either before or after HIV-1 infection, substantially inhibited p24 antigen production in HepG2 cells without causing any remarkable cytotoxicity. Gel-retardation assay revealed enhancement of a DNA-binding protein in TNF-alpha-treated HepG2 cells that binds to a specific sequence of the HIV-1 TAR, compared with the untreated control. CONCLUSIONS: These results indicate the importance of cellular factor(s) in HIV-1 infection and suggest that cytokines in different tissues can induce opposite effects. TAR-binding protein may act as an inhibitory factor for HIV-1 replication in the HepG2 cell line.

CD4 Antigens↗
PubMed1992

The role of differential class II antigen expression in stimulation of allogeneic mixed lymphocyte reactions by human monocyte hybridomas.

The recognition of foreign class II antigens on accessory cells is the crux of an alloreactive immune response. This phenomenon is clearly demonstrated in the primary mixed lymphocyte reaction, which correlates with the type and density of expressed gene products of the HLA-D region. We have generated a series of human monocyte hybridomas by fusing monocytes with the hypoxanthine guanine phosphoribosyl transferase (HGPRT)-deficient, HLA-D antigen-negative U937 histiocytic cell line. Clones bearing combination of HLA-DQ, -DP with or without HLA-DR have been isolated, allowing for the functional assessment of these molecules. In contrast to the U937 cells, the HLA-DR+DQ+DP+ clone 16.1 was capable of stimulating a primary allogeneic MLR. Interestingly, the DR- but DP+DQ+ clones 13 and 15 were also capable of stimulating alloreactive T cells, and the addition of anti-DQ or -DP but not -DR was associated with significant inhibition of the MLR response. Furthermore, gamma-IFN was found to have diverse effects on class II antigen expression in the U937 cells and the hybrids. gamma-IFN down-regulated the expression of HLA-DQ, -DP without altering -DR on clone 16.1, and this was associated with a significant reduction in its MLR stimulatory capacity. The MLR generated by this gamma-IFN-stimulated hybridoma (HLA-DR+DQ-DP-) was now unaffected by the addition of anti-DQ or -DP mAbs. In contrast, up-regulation of DQ and DP antigens on the U937 cells by gamma-IFN now rendered these cells stimulatory in MLR. These data are consistent with the concept that DQ and DP are both important allostimulatory determinants. Our results stress the potential importance of all D-region molecules in acute allograft rejection or successful engraftment.

Antibodies↗
PubMed1992

Lung function in retired coke oven plant workers.

Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants.

Aged↗
PubMed1992

In vivo detection of a novel macrophage-derived protein involved in the regulation of mucus-like glycoconjugate secretion.

We previously described a novel 68,000 D macrophage-derived protein (MMS-68) that can stimulate mucus-like glycoconjugate (MLGC) secretion from cultured human airways, respiratory epithelial cells, and the ishikawa adenocarcinoma cell line. To better characterize this mucus secretagogue, we generated monoclonal antibodies against MMS-68 by injecting crushed SDS-PAGE gel slices containing this protein into Balb-C mice followed by fusion with SP2/0, a nonsecreting mouse myeloma cell line. A panel of monoclonal antibodies was produced that identified the 68,000 D MMS by immunoblot analysis and immunoprecipitation. The monoclonal antibodies detected MMS-68 in normal peripheral blood monocytes and pulmonary macrophages by cytofluorographic analysis and in human airways as determined by immunohistochemistry. Utilizing the monoclonal antibodies, an antigen-capture ELISA assay was developed. Statistically significant elevations in levels of MMS-68 were detected in bronchoalveolar lavage fluid (BALF) of chronic bronchitic subjects and cigarette smokers and in monocyte culture supernatants from steroid-dependent asthmatic patients compared to normal control subjects. The 68,000 D MMS is a potent secretagogue and may play an important role in the regulation of mucus secretion, especially in chronic bronchitis and steroid-dependent asthma.

Adult↗
PubMed1991

The generation and characterization of human monocyte hybridomas.

Fusion of interferon-gamma activated peripheral blood monocytes to a mutagenized hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient U937 parent line was performed resulting in the generation of a series of unique cloned monocyte hybridomas. These cell lines were proven to be true hybrids by the acquisition of donor class I antigens as well as other donor derived chromosomes. In addition, novel functional characteristics were observed including secretion of specific monokines and the acquisition of phagocytic capabilities. The ability to generate immortalized human monocyte hybridomas will allow for more in depth analysis of monocyte subpopulations and dissection of specific monocyte functions.

Analysis of Variance↗
PubMed1991

Expression of class II molecules on intestinal epithelial cells in humans. Differences between normal and inflammatory bowel disease.

Expression of class II antigens on human intestinal epithelial cells was assessed using a sensitive avidinbiotin-peroxidase technique. HLA-DR was present predominantly in the normal small bowel with diminished but evident expression in the colon. HLA-DP staining was less prominent, and HLA-DQ was absent. In inflammatory bowel disease the expression of both HLA-DR and HLA-DP was increased, but that for HLA-DQ remained absent, suggesting an inherent defect in the ability of intestinal epithelial cells to express HLA-DQ. In related experiments, an interferon gamma-treated malignant epithelial cell line T84 also failed to stain for HLA-DQ and HLA-DP despite the presence of HLA-DR. Isolated RNAs for all three subclasses of HLA-D were detectable by slot-blot analysis, suggesting that the lack of HLA-DQ expression relates to posttranscriptional defects in intestinal epithelium. These and other differences with conventional class II antigen-positive accessory cells (macrophages/B cells) may help to explain the unique properties of intestinal epithelial cells as antigen-presenting cells.

Adenocarcinoma↗
PubMed1991

Expansion of a suppressor T-cell population associated with the hyper-IgM syndrome and generalized lymphadenopathy.

Immunoglobulin deficiency with increased IgM (hyper-IgM recurrent infection syndrome) is thought to be due to a defect of IgM/IgG isotype switching in B cells. Considerable genetic heterogeneity (X-linked, autosomal dominant or autosomal recessive inheritance, acquired forms) exists. We describe a case of hyper-IgM syndrome associated with massive lymphadenopathy in a 10-year-old girl with normal B-cell function. Absolute and relative increases of T-suppressor cells (CD8+) and a decrease of circulating CD4+ ("helper") cells were observed. The CD4+ cells present were all of the CD45R+ subtype, representing relatively immature ("naive") helper cells. In contrast, the number of CD4+ cells within the lymph nodes was increased. When tested fractionally, the patient's CD8+ cells selectively inhibited synthesis of IgG and IgA by normal B cells, but spared IgM. Normal allogenic T cells could induce IgG and IgA production by the patient's B cells. These findings suggest (a) a state of selective suppression of IgG and IgA synthesis with exclusive production of IgM, and (b) an abnormal recirculation of immature T-helper cells. This case represents a variant of this heterogeneous syndrome resembling the findings in neonatal lymphocytes and can be distinguished from the "adult" form of hyper-IgM syndrome which may be due to defective switch T cells.

Child↗
PubMed1991

Mucus secretagogue production by a human macrophage hybridoma.

A pulmonary macrophage-monocyte-derived mucus secretagogue (MMS) oligopeptide has been previously reported to induce mucus secretion in an in vitro model system with human airway explants and secretory epithelial cells. To understand the possible role of macrophages in the regulation of secretion of mucus, our laboratory has used a series of human macrophage hybridomas that were generated by fusing an hypoxanthine guanine phosphoribosyl transferase-deficient promonocytic line, U937, with macrophages obtaining by maturing monocytes in Teflon bags. The cell lines were proven to be true hybridomas by acquisition of donor class I antigens, additional chromosomes, as well as macrophage specific (maximum velocity) not present on the U937 parent line. One clone, clone 63, produced large amounts of an oligopeptide with an approximate molecular weight of 2000, which was identified from culture supernatants by ultrafiltration, chromatography, isoelectric focusing, and Western blot. Processed clone 63 supernatant had biologic activity causing increased secretion of radiolabeled glycoconjugate in both cultured airways and secretory epithelial cells. Immunoblot analysis with a polyclonal rabbit antisera generated against MMS was positive, and Western blot analysis produced a band at approximately 2000 daltons, consistent with the previously described MMS. MMS secretion could be stimulated by zymosan and lipopolysaccharide and inhibited by both cycloheximide and erythromycin. Dexamethasone had a different effect, appearing to stimulate MMS production intracellularly but inhibiting its release once it was synthesized. The availability of cloned hybridomas allows for study of the regulation of mucus secretagogue production as well as purification of molecular species and provides a valuable tool for the study of mucus secretion.

Cell Line↗
PubMed1991

Cytokines regulating human B cell growth and differentiation.

Utilizing a model system of anti-CD3-stimulated T cells, we have identified a potent B cell differentiation factor (BCDF) in the supernatant of these cells. This factor, 446-BCDF, appears to act on SAC-activated B cells inducing a 10- to 100-fold increase in Ig secretion. 446-BCDF has an apparent MW of 32 kDa and a pI of 6.0. Its activity cannot be inhibited by an anti-IL-6 antiserum, and activity is enhanced after passage over an anti-IL-6 affinity column. 446-BCDF activity is detected in the 50 mM salt fraction eluted from a Mono Q column. This 50 mM fraction has the only activity detected after passage over an anti-IL-6 affinity column and migrates with an apparent pI of 6.0. Taken together these data suggest that 446-BCDF is a unique potent polyclonal human BCDF which may be a predominant factor regulating terminal B cell differentiation.

Antibodies, Monoclonal↗
PubMed1991

Correlation of spontaneous suppressor cell activity with progression of human immunodeficiency virus infection.

The immune system has been extensively evaluated in the acquired immunodeficiency syndrome (AIDS). The central role of the T-helper (CD4) cell in the immunopathogenesis of AIDS and the immunologic markers that can predict human immunodeficiency virus (HIV) disease progression have been described. However, the potential influence of suppressor cells in this disease process has not been clearly addressed. Spontaneous suppressor cell activity (SSCA) was evaluated in 78 patients with documented HIV infection at different clinical stages of disease progression. Higher levels of SSCA were found in patients with clinical AIDS less than 6 months and those dying of AIDS when compared with controls. Significant elevations (p less than 0.05) of SSCA were seen in patients newly diagnosed with AIDS, and those having AIDS greater than 6 months and less than one year. Patients surviving AIDS for greater than one year had depressed levels of SSCA compared to controls. Furthermore, SSCA appears to predict disease progression as patients with AIDS-related complex (ARC) with elevations in SSCA progressed to AIDS while those with blunted SSCA did not progress. The level of SSCA in these patients was able to predict disease progression (p = 0.00016, Pearson correlation coefficient = 0.739). Patients with documented AIDS were also followed prospectively, and the level of SSCA was shown to be predictive of mortality (p = 0.009, Pearson correlation coefficient = 0.746). It is concluded that SSCA is a valid predictor of disease progression, and can serve as a prognostic indicator of disease outcome.

AIDS-Related Complex↗
PubMed1991

Stimulation of distinct T cell subsets in MLR using human macrophage hybridomas differentially expressing class II antigens.

Recognition of class II antigens by alloreactive T cells is thought to be the major mechanism by which tissues undergo rejection. However, the specific role of the various class II antigens in the stimulation of these alloreactive cells remains to be elucidated. We have recently generated a series of human monocyte hybridomas that express distinct patterns of class II antigen expression. HLA-DR+ as well as HLA-DR-DP+DQ+ hybrids were capable of promoting T cell proliferation in a unidirectional mixed lymphocyte reaction. T cells stimulated by the HLA-DR+ clone 16.1 were predominantly of the CD4 (helper/inducer) phenotype. In contrast, T cells stimulated by the HLA-DR-DP+DQ+ clone 13 appear to reside in the CD8+ T cell subpopulation. Functional assessment of the T cell blasts generated in these cultures demonstrated a predominant helper T cell effect by those T cells stimulated by the HLA-DR+ clone 16.1, while suppressor cell activity was exhibited by T cells stimulated with the HLA-DR-DP+DQ+ clone 13. These data suggest that there may be a differential role for distinct class II molecules in the stimulation of T cell subpopulations.

Antibodies, Monoclonal↗
PubMed1991

Evidence for accessory cell function by class II MHC antigen-expressing airway epithelial cells.

Expression of major histocompatibility complex (MHC) class II antigens is a requirement for accessory cell function in antigen presentation. Recent reports have demonstrated the presence of class II antigens on human bronchial epithelial cells. In the present study, immunohistochemical staining revealed HLA-DR on human airway epithelial cells obtained from two different mucosal sites (lobar bronchus and nasal turbinates). To determine whether airway epithelial cells bear functional class II molecules that allow for their cognate interaction with T lymphocytes, cells isolated from these sites were used in mixed lymphocyte cultures (MLR), as an in vitro model of accessory cell function. Freshly isolated cells (11 bronchi/3 turbinates) stimulated allogeneic T lymphocytes (stimulation index [S.I.] = 9.3 [mean]; P less than 0.001 compared to T cells alone). In order to assess the potential role of contaminating conventional accessory cells, bronchial epithelial cell isolates were first preincubated in a serum-free, growth factor-supplemented medium that functionally eliminates potential non-epithelial stimulators prior to MLR culture. Conventional accessory cell-depleted epithelial cells were still capable of stimulating allogenic T lymphocytes in 18 of 23 MLR cultures (S.I. = 5.5 [mean]; P less than 0.0005 compared to T cells alone). The addition of an anti-class II monoclonal antibody (VG2.2) at the onset of culture completely inhibited the MLR response (n = 10). No shift in the CD4+/CD8+ ratio was detected between lymphocytes harvested from airway epithelial cell MLR (1.42 +/- 1.29) and the ratio from T lymphocytes cultured alone (1.3 +/- 0.75), suggesting that both CD4+ and CD8+ T lymphocytes were proliferating in response to stimulation from alloepitopes recognized on airway epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗