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Biomedical subjects

L Mayer

Publications and source records attributed to L Mayer.

At least 127 records · Page 7Linked to original sources
PubMed1990

Identification of subpopulations of human macrophages through the generation of human macrophage hybridomas.

We have generated a series of human macrophage hybridomas by fusing an HGPRT-deficient promonocytic cell line, U937, with macrophages obtained by allowing monocytes to mature into macrophages in teflon bags. The fusions were documented as true hybrids by the acquisition of donor class I molecules, as well as donor derived macrophage surface antigens. The hybridomas represent clonal expansion of individual macrophages, retaining the surface antigen expression and functional capacity of the normal donor cells including cytokine production and stimulation in a mixed lymphocyte reaction. These cell lines differentially express Vmax antigens found on normal macrophages, potentially identifying subpopulations of macrophages. These lines may be useful not only to study normal macrophage function but may be relevant to a variety of disease states where expansion of subpopulations of macrophages identified by Vmax antigens may be important in disease pathogenesis.

Antibodies, Monoclonal↗
PubMed1990

CD5 and immunoglobulin V gene expression in B-cell lymphomas and chronic lymphocytic leukemia.

We studied the expression of CD5 and immunoglobulin variable gene families in a panel of monoclonal Epstein-Barr virus (EBV) transformed lines, chronic lymphocytic leukemias (CLLs) and CD5+ and CD5- B-cell lymphomas. The CD5 gene expression was in all cases identical to that of T-cell malignancies. The utilization of the various VH and VK gene families was roughly proportional to the estimated gene family size in EBV lines obtained from adult healthy subjects. In contrast we found a statistically significant biased usage of VH6 in CLL and VH5 in CD5+ lymphomas as compared with EBV lines, and of VKIII in both CLL and CD5+ lymphomas as compared with EBV lines. Some differences in the variable gene usage were also noted when comparing CD5+ and CD5- lymphomas. These findings are analyzed in the context of possible mechanisms involved in the malignant transformation of CD5+ B cells.

Antigens, CD↗
PubMed1990

Interleukins 1 and 3 stimulate anion secretion in chicken intestine.

Interleukin 1 or 3 added to the serosal side of chicken small intestine transiently increases short-circuit current. Replacement of bathing-medium Cl and HCO3 with gluconate and HEPES abolished the short-circuit current increase, consistent with these cytokines stimulating electrogenic anion secretion. Cytokine-stimulated short-circuit current changes were inhibited by preincubation with piroxicam (10(-5) M), an inhibitor of arachidonic acid cyclooxygenase, suggesting prostaglandin formation as an intermediate step for cytokine stimulation of short-circuit current. In intact mucosal strips, interleukin 1 and 3 stimulated prostaglandin E2 release and elevated tissue 3',5'-cyclic adenosine monophosphate concentration. When prostaglandin E2 release from epithelial and subepithelial fractions of the mucosa by interleukin 1 was determined, increases were found only from the subepithelium. The secretory actions of cytokines appear to be mediated by arachidonic acid metabolites most likely produced by cells of the lamina propria and submucosa and may play a role in inflammatory processes in which intestinal secretion is enhanced.

Action Potentials↗
PubMed1990

Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease.

The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occurring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn's disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn's and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Surface expression of CD-4 does not predict susceptibility to infection with HIV-1 in human monocyte hybridomas.

In contrast to T-cell lines, where CD-4 expression may predict susceptibility to HIV infection, in monocyte hybridomas, presence or absence of surface CD-4 does not appear to be the determining factor of susceptibility to HIV infection. One clone, 20, was documented to be CD-4 negative by surface immunofluorescence as well as by immunoprecipitation. Both CD-4+ and CD-4- human monocyte hybridomas, representative of peripheral blood monocytes were readily infected with HIV (strains IIIB and BR-1 and a variety of patient isolates) as assessed by p24 Ag secretion reverse transcriptase activity and in situ hybridization. Infection occurred in the absence of antibody to HIV suggesting a non Fc mediated process as had been previously described. These data suggest that alternative mechanisms, such as non-specific phagocytosis, may exist for entry of HIV into peripheral blood monocytes. Given these findings, treatment for AIDS, such as the use of soluble CD-4, may not be effective long term, as monocyte infection may still occur and serve as a reservoir for subsequent viral infection of T cells.

CD4 Antigens↗
PubMed1989

Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes.

IL-6 is a cytokine with pleiotropic biological functions, including induction of the hepatic acute phase response and differentiation of activated B cells into Ig-secreting plasma cells. We found that human peripheral blood monocytes express the IL-6-R, which is undetectable on the large majority of lymphocytes of healthy individuals. Stimulation of monocytes by endotoxin or IL-1 causes a rapid downregulation of IL-6-R mRNA levels and a concomitant enhancement of IL-6 mRNA expression. IL-6 itself was found to suppress the IL-6-R at high concentrations. A gradual decrease of IL-6-R mRNA levels was observed along in vitro maturation of monocytes into macrophages. We show that downregulation of IL-6-R mRNA levels by IL-1 and IL-6 is monocyte specific, since IL-6-R expression is stimulated by both IL-1 and IL-6 in cultured human primary hepatocytes. Our data indicate that under noninflammatory conditions, monocytes may play a role in binding of trace amounts of circulating IL-6. Repression of monocytic IL-6-R and stimulation of hepatocytic IL-6-R synthesis may represent a shift of the IL-6 tissue targets under inflammatory conditions.

Blotting, Northern↗
PubMed1989

Characterization of lymphokines mediating B cell growth and differentiation from monoclonal anti-CD3 antibody-stimulated T cells.

Addition of anti-CD3 mAb 147 (IgG1), 446 (IgG1), or 454 (IgG2a) to cultures of T plus non-T cells can result in both B cell growth and differentiation. To determine whether lymphokines mediating these activities were similar to those described from conventional mitogen-induced T cell activation, normal peripheral blood T cells were stimulated with anti-CD3 mAb for 48 h. The supernatants were assayed for factors inducing B cell growth or differentiation (BCDF). A marked increase in Ig secretion was observed when either EBV-transformed B cell lines or normal B cells, pre-activated with Staphylococcus aureus Cowan I strain, were cultured in the presence of mAb 446 (anti-CD3) stimulated T cell supernatant whereas no significant increase in Ig secretion was noted with either mAb 454- or 147-induced T cell supernatant despite equivalent T cell proliferative responses to these antibodies. In contrast, IL-2 secretion was detectable in T cell supernatants from T cells stimulated with either mAb 454 or 147 but not 446. Factors promoting B cell proliferation were detected in all antibody-stimulated T cell supernatants but, contrary to BCDF, appear to act only on non-activated B cells. To determine whether these effector activities were due to distinct lymphokines, supernatants were pooled and concentrated by ammonium sulfate precipitation. Superose 12 permeation chromatography revealed BCDF activity with an apparent Mr of approximately 30,000 Da. The growth factor activity eluted over a wider and higher molecular weight range which overlapped the differentiation factor activity. Fractions containing BCDF activity were pooled, dialyzed, applied to a Mono Q anion-exchange column, and eluted with a linear NaCl gradient. The growth factor activity came off in a single-peak while BCDF was found divided into two major areas. The growth factor eluted at an ionic strength between the two BCDF activities. BCDF has an apparent isoelectric point (pI) of 6, in contrast to the reported pI 5 for IL-6 and more acidic than the documented basic pI of IFN-gamma. Lastly, peaks with BCDF activity were not active in assays for either IL-2 or IL-4. In addition, a rabbit anti-IL-6 heteroantiserum failed to inhibit the pI 6 BCDF, suggesting non-identity between IL-6 and anti-CD3 induced BCDF. Thus, anti-CD3 activated T cells generate both growth factor activity and BCDF as separate molecular entities distinct from IFN-gamma, IL-2, IL-4, and conventional IL-6.

Antibodies, Monoclonal↗
PubMed1989

Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation.

The molecular mechanism by which interleukin 6 (IL-6) induces terminal differentiation of B cells was investigated in a subpopulation of the clonal human B-lymphoblastoid cell line CESS selected for high density of cell surface IgG1. Induction of CESS cells with IL-6 resulted in a 15-fold preferential accumulation of secreted-specific gamma 1 (gamma 1s) mRNA but not of the alternatively processed membrane-specific gamma 1 (gamma 1m) mRNA. Similarly, microseconds mRNA but not the microns mRNA of the nonproductively rearranged mu heavy-chain allele was also increased. Accompanying the differential accumulation of gamma 1s mRNA was a 4.5-fold increase in lambda light-chain mRNA, leading to secretion of IgG1. Analyses of transcription in isolated nuclei demonstrated that transcriptional activation was the primary mechanism for quantitative increase of immunoglobulin mRNAs (5.5-fold for gamma 1 and mu and at least 2-fold for lambda). Since polymerase loading is diminished by 75% before reaching the downstream gamma 1m polyadenylylation site in CESS cells, irrespective of IL-6 induction, transcriptional pausing/termination appears intrinsic and contributes to the selection of gamma 1s and gamma 1m polyadenylylation sites in activated B cells. Furthermore, differential mRNA stabilization is likely to contribute to the alteration of the gamma 1s/gamma 1m mRNA ratio at IL-6 induction.

B-Lymphocytes↗
PubMed1989

Feedback inhibition of B cell differentiation by monomeric immunoglobulin.

Polyspecific monomeric immunoglobulin (Ig) isolated from either a commercial source (pooled, > 2000 donors), or an autologous donor was capable of inhibiting both B cell proliferation, induced by T dependent mitogens or T cell factors and B cell differentiation, induced by similar stimuli. These effects appear to be directed at the B cell itself since inhibition of differentiation is detectable when monomeric Ig is added to cultures of B cell lines in the presence of B cell differentiation factor (BCDF). The inhibition of B cell differentiation does not appear to relate to inhibition of B cell proliferation, as no detectable change is seen in thymidine incorporation or cell number in these cultures. Furthermore, the effect of monomeric lg appears to relate to an early event in B cell differentiation, as there is no effect of IgSRK on spontaneously secreting B cell lines and maturation to cytoplasmic Ig containing cells is markedly impaired. Therefore, monomeric Ig secreted by B cells may serve as an immunoregulator of further Ig secretion.

Antibody Formation↗
PubMed1989

Umbilical cord blood serosurvey for human immunodeficiency virus in parturient women in a voluntary hospital in New York City.

The potential spread of the human immunodeficiency virus (HIV) to childbearing women in areas of high acquired immunodeficiency syndrome (AIDS) endemicity is a major public health concern. As a private institution providing obstetric care to such a population of women, we undertook an anonymous HIV cord blood serosurvey to estimate the number of childbearing women at our institution at risk for perinatal transmission of the virus and to assess the success of our voluntary screening program to identify seropositive women. Between November 1987 and January 1988, cord blood samples from all clinic deliveries were analyzed for the presence of HIV antibody. For each sample obtained, the mother's age and site of prenatal care were known. Overall, 2.7% (six of 224) of the samples tested were seropositive; two of the 34 samples (5.9%) from teenage mothers were seropositive. All positive samples were from women who received prenatal care; none were identified through a voluntary screening program based on patient self-acknowledged risk-behavior assessment. This confirms that risk factor history elicited by personal interview is not a reliable screening tool for initiating HIV antibody counseling and testing. The high seropositive rate in teenagers is disturbing and needs further assessment.

AIDS Serodiagnosis↗
PubMed1988

In vitro induction of T cell-dependent B cell differentiation in patients with common varied immunodeficiency.

Patients with common varied immunodeficiency (CVI) are characterized by hypogammaglobulinemia. We investigated in vitro T cell-dependent B cell differentiation in CVI peripheral blood mononuclear cells by stimulating the T cells with an anti-CD3 (T3) monoclonal antibody. In cultures from CVI patients with no detectable circulating B cells, little immunoglobulin (Ig) was produced following anti-CD3 stimulation. In cultures from CVI patients with near-normal numbers of circulating B cells, anti-CD3 stimulation induced a normal percentage increase in Ig-secreting cells and appreciable (albeit subnormal) increases in IgG and IgM secretion. Cell-mixing experiments pointed to a quantitative, rather than qualitative, defect in B cell function in most of these CVI patients. Nevertheless, CVI T cells can induce substantial differentiation of autologous (and normal) B cells following anti-CD3 stimulation (which may mimic physiologic stimulation). This raises the possibility of correcting the hypogammaglobulinemia of CVI by in vivo or ex vivo administration of appropriate T cell stimuli.

Adolescent↗
PubMed1988

Extraintestinal manifestations in patients with diverticulitis.

Three patients had diverticulitis and extraintestinal manifestations of arthritis and pyoderma gangrenosum. In each, a mistaken diagnosis of idiopathic inflammatory bowel disease was first made because of extraintestinal complaints associated with the gastrointestinal symptoms of diverticular disease. The joint and skin manifestations were refractory to various treatments, including oral and intradermal steroids, immunosuppressive agents, and hyperbaric oxygen. Segmental resection of the involved colon promptly and completely resolved all symptoms, without recurrence 26 to 38 months after surgery. Microscopic examination of the resected specimens showed only diverticulitis without any evidence of chronic idiopathic inflammatory bowel disease. Patients with diverticulitis may have extraintestinal manifestations as do patients with other inflammatory diseases of the colon. The failure to recognize this relationship may result in misdiagnosis and prolonged medical therapy, whereas segmental colonic resection may be curative.

Aged↗
PubMed1987

Massive outbreak of antimicrobial-resistant salmonellosis traced to pasteurized milk.

Two waves of antimicrobial-resistant Salmonella typhimurium infections in Illinois totaling over 16 000 culture-confirmed cases were traced to two brands of pasteurized 2% milk produced by a single dairy plant. Salmonellosis was associated with taking antimicrobials before onset of illness. Two surveys to determine the number of persons who were actually affected yielded estimates of 168 791 and 197 581 persons, making this the largest outbreak of salmonellosis ever identified in the United States. The epidemic strain was easily identified because it had a rare antimicrobial resistance pattern and a highly unusual plasmid profile; study of stored isolates showed it had caused clusters of salmonellosis during the previous ten months that may have been related to the same plant, suggesting that the strain had persisted in the plant and repeatedly contaminated milk after pasteurization.

Adolescent↗