Search PubMed⌕ Search

Biomedical subjects

L Mayer

Publications and source records attributed to L Mayer.

At least 91 records · Page 5Linked to original sources
PubMed1994

Stimulation of lamina propria lymphocytes by intestinal epithelial cells: evidence for recognition of nonclassical restriction elements.

We have addressed the restriction elements involved in the interaction of lamina propria lymphocytes (LPL) and intestinal epithelial cells using the model of primary mixed cell culture reaction. Whereas peripheral blood T cells proliferate in response to both allogeneic non T cells and class II antigen-bearing intestinal epithelial cells (non T cells >> epithelial cells), LP T cells appear to proliferate preferentially in response to intestinal epithelial cells. The interaction between these cells does not appear to be restricted by conventional products of the major histocompatibility complex as neither monoclonal antibodies to class I nor to class II antigens inhibit the mixed cell cultures, whereas they are inhibitory in conventional mixed lymphocyte reactions. Furthermore, treatment of epithelial cells with interferon gamma fails to augment the cells' ability to induce proliferation of LPL while successfully enhancing proliferation of peripheral blood T cells in parallel cultures. Taken together, these data suggest that alternate restriction elements or mucosa-specific accessory molecules may exist on intestinal epithelial cells that are preferentially recognized by LPLs. Such a distinct regulatory network may be critical to the maintenance of immunologic homeostasis in the gut.

Cell Communication↗
PubMed1994

Impairment of monocytic function during Trypanosoma cruzi infection.

During acute infection, Trypanosoma cruzi, the etiologic agent of Chagas' disease, causes immunosuppression by mechanisms that are not fully delineated. Since mononuclear phagocytes are major target cells in trypanosomiasis, we investigated monocytic function during acute T. cruzi infection. A series of human monocyte and macrophage hybridomas, which represent clonal expansions of subpopulations of human macrophages and possess many normal monocytic functions, were successfully infected with T. cruzi. Clones 63 and 53, chosen for stability in long-term culture, were studied extensively after infection with T. cruzi. Following infection of clone 63, the trypomastigote did not transform into the amastigote multiplicative form, suggesting that clone 63 did not support the entire T. cruzi life cycle. The typical life cycle was completed in clone 53, and thus, clone 53 was used in subsequent studies. Following infection, clone 53 lost expression of class II antigens compared with uninfected cells (DR of 2.2% versus 29.3% and mean channel fluorescence intensity [mean channel] of 4.1 versus 30.5, DQ of 2.3% versus 15.6% and mean channel of 5.4 versus 11.4, and DP of 6.3% versus 27.2% and mean channel of 10.3 versus 33.4). The expression of Class I antigens (87.9% versus 82.8%; mean channel, 20 versus 120) and the adhesion molecules LFA-1 (72.9% versus 28.7%; mean channel, 50.7 versus 23.7) and LFA-3 (10.8% versus 0.7%; mean channel, 20.7 versus 15.1) was increased in infected cells compared with that in uninfected cells. Production of interleukin-1 alpha was decreased and interleukin-6 production was increased in infected clone 53 compared with those in the uninfected cells, while production of tumor necrosis factor alpha was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Evidence for an altered T-cell receptor repertoire in Crohn's disease.

We have compared the frequencies of T cells expressing each of four different T cell receptor (TCR) V beta segments in lamina propria and peripheral blood lymphocytes of 12 Crohn's disease (CD), six ulcerative colitis (UC), and 10 control patients in an attempt to identify disease-specific changes. The frequencies of CD4+ and CD8+ cells reacting with each of four fluoresceinated TCR-specific monoclonal antibodies directed against V beta 5, V beta 6.7a, V beta 8, and V beta 12 were determined by flow cytometry. There was no difference among the groups in the average frequency of any single V beta segment in either the CD4+ or CD8+ subpopulations. However, when the sum of the differences in V beta frequencies (delta score) between peripheral blood lymphocytes (PBL) and lamina propria lymphocytes (LPL) were determined for each individual, significant differences were observed between the CD4+ and CD8+ populations and among the patient groups. In all three patient groups, there were significant individual differences between LPL and PBL in the frequencies of CD8+ and CD4+ cells reacting with the four V beta-specific mAb. In Controls and UC, this difference was, on average, two-fold greater in CD8+ cells than in CD4+. In CD, however, this difference was, on average, the same for CD8+ and CD4+ cells. These observations suggest that (1) the human colonic LPL TCR repertoire is normally different from that of PBL, especially in the CD8+ population and (2) there is an alteration in the LPL TCR repertoire in CD which is not observed in Controls or UC.

Antibodies, Monoclonal↗
PubMed1993

CD1d is involved in T cell-intestinal epithelial cell interactions.

We assessed the role of the nonclassical class I molecule, CD1d, in the interaction between intestinal epithelial cells and T cells. In a mixed lymphocyte reaction (MLR) system where the stimulator cells were irradiated normal intestinal cells, the anti-CD1d monoclonal antibody (mAb) 3C11 inhibited T cell proliferation. In contrast, no inhibition was seen when mAb 3C11 was added to conventional MLR cultures (non T cell stimulators). Furthermore, no inhibition was seen when either airway epithelial cells were used as stimulator cells or lamina propria lymphocytes were used as responder cells. These latter two conditions along with a conventional MLR favor CD4+ T cell proliferation. However, we have previously shown that normal intestinal epithelial cells stimulate CD8+ T cells under similar culture conditions. Thus, CD1d expressed on intestinal epithelial cells may be an important ligand in CD8+ T cell-epithelial cell interactions.

Antibodies, Monoclonal↗
PubMed1993

T-cell activation in human intestinal mucosa: the role of superantigens.

BACKGROUND: Superantigens are a class of potent T-cell mitogens that activate T cells using specific antigen receptor V regions. Superantigens have been implicated in the pathogenesis of several autoimmune diseases, including inflammatory bowel disease. The present study examines the role of superantigens in the human gastrointestinal immune response. METHODS: Human intestinal epithelial cells and T lymphocytes were obtained from surgical specimens and cultured in the presence or absence of exogenous superantigens. Activation of T cells and V region usage were measured by thymidine incorporation and by cell staining using a panel of monoclonal antibodies. RESULTS: Neither epithelial cells from normal nor diseased intestinal mucosa expressed virally encoded, endogenous superantigens. However, 50% of epithelial cell preparations could present exogenous bacterial superantigens to T cells. In the other 50%, a defect in this function was observed, which did not represent production of suppressive factors or absence of accessory cytokines. Mucosal T lymphocytes proliferated in response to superantigens in vitro, expressing increased transferrin receptor, interleukin-2 receptor, and HLA-DR. CONCLUSIONS: A superantigen-driven mucosal immune response may occur in health and in chronic inflammatory states. The intestinal epithelial cell may mediate this response, through presentation of superantigens to mucosal T lymphocytes.

Antigen-Presenting Cells↗
PubMed1993

A novel human macrophage-derived intestinal mucin secretagogue: implications for the pathogenesis of inflammatory bowel disease.

BACKGROUND: A novel 68-kilodalton macrophage-derived protein (MMS-68) stimulating mucin release from respiratory epithelial cells has previously been described. In this study, the effect of MMS-68 on mucin release from intestinal epithelial cells was determined. METHODS: Colonic epithelial cells isolated from normal colon, ulcerative colitis, Crohn's colitis, and cells from three colon cancer cell lines were labeled with [3H]-glucosamine and stimulated with MMS-68. High molecular weight glycoproteins were precipitated and counted. RESULTS: In all of the cells tested, MMS-68 enhanced mucin secretion by 1.46-2.0-fold above control values, comparable to the level achieved with carbachol (10(-5) mol/L). Coincubation with anti-MMS-68 monoclonal antibody 1D-10 blocked this bioactivity. Freshly isolated intestinal macrophages reacted with monoclonal antibody 1D-10. Immunofluorescent staining of frozen sections revealed the presence of MMS-68-producing cells (macrophages) in the lamina propria of normal colon and Crohn's colitis, with weaker expression in ulcerative colitis mucosa. CONCLUSIONS: Intestinal macrophages produce a novel mucin secretagogue, which is as potent as carbachol for stimulating mucin secretion from colonic epithelial cells. This factor may explain, in part, the alterations in mucin secretion often seen in inflammatory bowel disease.

Antibodies, Monoclonal↗
PubMed1993

Progressive impairment of monocytic function in HIV-1-infected human macrophage hybridomas.

Using human macrophage hybridomas infected with HIV-1, we investigated monocyte function over a 5-week period after HIV-1 infection. Two clones, 63 and 30, were infected with HIV-1IIIB. Infection was documented by RT activity (15 x 10(6) cpm/ml), intracytoplasmic staining with an anti-p24 antibody, in situ hybridization with an HIV-1-specific riboprobe, and electron microscopy showing intracytoplasmic virus. Two weeks after infection, clones 63 and 30 lost expression of all class II antigens (DR, 81.7 vs. 0%; DQ, 15.6 vs. 0%; and DP, 76.9 vs. 0%) while retaining expression of class I (87.4 vs. 84.1%), LFA-1 (82.4 vs. 83.1%), and LFA-3 (79.1 vs. 74.7%) antigens when compared to uninfected cells. When tested for functional integrity, infected but not uninfected clone 63 cells failed to stimulate a tetanus-specific MHC-restricted T cell proliferative response 2 weeks after infection. Cytokine secretion and antigen processing were also perturbed as production of IL-1 was abolished 2 weeks after infection (although IL-6 secretion was augmented) and infected clone 63 cells failed to process exogenous antigen. Last, the viability of T cells cocultured with infected clone 63 was dramatically decreased 35 days after infection (85 vs. 15%). There was no evidence of transmission of HIV-1 to T cells, suggesting a toxic effect of infected clone 63. Taken together, these data suggest that altered macrophage function in our system occurs at multiple levels, which may account for the early immunological defects described in HIV-1 infection.

Antigen-Presenting Cells↗
PubMed1993

Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes.

Chloroquine and its analogue hydroxychloroquine (HCQ) have been shown to inhibit a variety of viral infections including influenza and adenovirus through blockade of viral entry via inhibition of endosomal acidification. We have extended these observations to human immunodeficiency virus type 1 (HIV-1) infection utilizing primary T cells and monocytes, a T cell line (CEM), and a monocytic cell line (U-937). HCQ inhibited HIV-1 replication (> 75%), as measured by reverse transcriptase activity, in the primary T cells and monocytes as well as the T cell and monocytic cell lines. HCQ itself had no anti-reverse transcriptase activity and was not toxic to the cells at concentrations inhibitory to viral replication. Intracytoplasmic staining with an anti-p24 antibody, 24 h after infection, revealed the presence of intracytoplasmic virus, suggesting that the drug does not block viral entry. The production of steady-state HIV-1 mRNA was not affected by HCQ in that comparable levels of HIV-1 mRNA could be detected by Northern blot analysis and by in situ hybridization in both the HCQ-treated and untreated cells. However, HCQ does appear to affect production of infectious HIV-1 virions because viral isolates from HCQ-treated cells could not infect target CEM cells. These data suggest that HCQ may be useful adjunctive therapy in the treatment of HIV-1 infection.

HIV-1↗
PubMed1993

Elder abuse and the dentists' awareness and knowledge of the problem--a national survey.

A national sample of 1,775 Canadian dentists, representing 13.2 per cent of all Canadian dentists, were evaluated via a mailed questionnaire about their knowledge, awareness of, and experiences with victims of elder abuse and/or neglect. In all, 83.3 per cent of respondents were aware, to varying extents, of elder abuse or neglect. Of the dentists observing a patient suspected to have been a victim of neglect or abuse, 40.6 per cent reported incidents of neglect, while physical abuse was seen 59.4 per cent of the time. The types of neglect most frequently observed included: neglect of personal hygiene (31.8 per cent), failure to provide adequate medical/dental care (30.2 per cent), and failure to provide adequate supervision (20.1 per cent). The most frequently reported signs of physical abuse were bruises and welts (21.8 per cent), broken denture prostheses (12.1 per cent), fractured and avulsed teeth (11.5 per cent), and abrasions and lacerations (10.3 per cent). Where abuse was observed, dentists provided dental treatment in 53.2 per cent of the cases and made emergency medical referrals in 20.3 per cent of the cases. This study demonstrates that dentists have identified cases of abuse and/or neglect, and therefore should be consulted in the abuse/neglect identification and assessment process.

Aged↗
PubMed1993

Indirect latex contact causes urticaria/anaphylaxis.

Recurrent urticaria/anaphylaxis is a most perplexing and critical problem, often of unknown cause. Though difficult and time consuming, identification of causes(s) can be life saving and cost saving for the patient(s). We report a complex case of urticaria/anaphylaxis induced by latex allergen in a former intensive care unit nurse, in which the allergen contact occurred remotely and indirectly by intimate contact with the spouse. Diagnosis of the latex allergy was confirmed by epicutaneous skin test in vivo as well as RAST.

Adult↗
PubMed1993

Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells.

To study the effect of hydroxychloroquine on cytokine production by monocytes and T cells, cells were pretreated with varying concentrations of hydroxychloroquine and stimulated with lipopolysaccharide (monocytes), phytohemagglutinin or anti-CD-3 monoclonal antibodies (T cells). Interleukin 1 alpha (IL-1-alpha), IL-6 and tumor necrosis factor alpha (TNF-alpha) production were measured from the stimulated monocytes and IL-2, IL-4 and gamma interferon (IFN-gamma) were measured from the stimulated T cells. Hydroxychloroquine inhibited production of IL-1-alpha (monocytes) and IL-6 (T cells and monocytes). In contrast IL-2, IL-4, TNF-alpha and IFN-gamma production were not affected. Preferential inhibition of IL-1-alpha production by monocytes and IL-6 production by T cells and monocytes may contribute to its antiinflammatory effect in autoimmune diseases.

Cytokines↗
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↗