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S H Stein

Publications and source records attributed to S H Stein.

13 recordsLinked to original sources
PubMed1992

Anti-class II antibodies potentiate IgG2a production by lipopolysaccharide-stimulated B lymphocytes treated with prostaglandin E2 and IFN-gamma.

IFN-gamma secretion by Th1 cells has been shown to preferentially promote the production of IgG2a in LPS-stimulated murine B lymphocytes. We recently reported that PGE2 potentiated the ability of IFN-gamma to augment IgG2a production in both Ag-specific and polyclonal systems via a cAMP-dependent pathway. Because antibodies (Ab) directed against class II MHC molecules have been shown to induce a rise in B cell cAMP, we hypothesized that this event, like PGE2 treatment, would promote the production of IgG2a. In this manuscript, cultures of small and large B cells treated with anti-Ia Ab are shown to produce significantly higher levels of IgG2a, compared with cultures treated only with IFN-gamma and LPS. Moreover, the combined treatment of B lymphocytes with IFN-gamma and PGE2 followed by anti-Ia and LPS resulted in a fourfold rise in IgG2a levels compared with IFN-gamma and LPS. Only anti-class II, but not anti-class I Ab, stimulated IgG2a production. Utilizing an ELISA spot assay, the frequency of IgG2a-secreting B cells was determined to be elevated fourfold in anti-Ia treated B cells. B cell cultures incubated with either PGE2 or anti-Ia exhibited elevated levels of cAMP and treatment with IFN-gamma primed these lymphocytes to the cAMP-elevating effects of either PGE2 or anti-Ia. Finally, RpcAMP, a cAMP antagonist that blocks cAMP from activating protein kinase A, prevented the increased production of IgG2a induced by anti-Ia Ab. These results support the theory that a cAMP pathway exists that promotes B cell IgG2a production. Within this pathway, IFN-gamma sensitizes B lymphocytes to cAMP elevators such as anti-class II Ab, and in conjunction with LPS, causes an increase in the frequency of IgG2a-secreting cells and the amount of IgG2a produced. These observations suggest that, after exposure to viral Ag in vivo, interaction between IFN-gamma-primed murine B cells and T cells will potentiate production of IgG2a, the predominant murine anti-viral Ig.

Animals↗
PubMed1992

Examiner reliability for an invasive gingival bleeding index.

This investigation was undertaken to determine the intra- and inter-examiner reliability of the method of stimulation for bleeding used in the Eastman interdental bleeding index. 26 subjects were examined twice, 1 h apart, by either a single examiner or 2 examiners in each half of their mouths, for the presence bleeding after stimulation with a wooden interdental cleaner. Scores were tabulated and intra- and inter-examiner % agreements and kappa-coefficients calculated. Z-tests were performed on the pairs of agreement statistics to check for significant differences. Overall, intra-examiner agreement statistics were high (91.3% to 93.1% agreement; 0.79 to 0.86 kappa-coefficient). Further breakdowns of the data into facial and lingual sites by arch and location (anterior or posterior) resulted in similar levels of reliability, with no significant differences within examiners. The overall inter-examiner agreement statistics were good (82.8% to 87.6% agreement; 0.62-0.75 kappa coefficient). When inter-examiner data were analyzed at facial or lingual sites by arch and location, a significant difference existed in reliability for mandibular posterior lingual sites, but reliability was high in all other areas. These data demonstrate a high level of reproducibility for this method, which suggests that the Eastman interdental bleeding index is suitable for clinical trials and epidemiologic studies of interdental gingivitis.

Adult↗
PubMed1991

Antigen-specific IGG2A production in response to prostaglandin E2, immune complexes, and IFN-gamma.

Immune complexes (IC) can inhibit the differentiation of B lymphocytes into IgM secreting plasma cells in both Ag-specific and polyclonal systems. This report describes the ability of IC and IFN-gamma, or IFN-gamma and PGE2 to regulate the class of Ig produced in an Ag-specific system. In an in vitro model system using fluorescein (FL)-Brucella abortus as Ag, we previously showed that IC composed of an anti-FL antibody and FL-Ag inhibited the ability of FL-specific B cells to develop into IgM plaque-forming cells. In addition, PGE2 sensitized resting B cells to IC, whereas pretreatment with IL-4 alleviated the IC-mediated decrease in the IgM anti-FL response. In this manuscript, we demonstrate that IFN-gamma has antagonistic effects compared to IL-4, and potentiates the IC-induced decrease in the IgM antibody response. Interestingly, we discovered that the virtual ablation of the anti-FL IgM response exhibited by B cells treated with IC and IFN-gamma was accompanied by a dramatic increase in the anti-FL IgG2a response. Furthermore, resting B lymphocytes pulsed with IFN-gamma and PGE2, but not PGF2 alpha, exhibited augmented IgG2a production. This effect was also observed when IFN-gamma-pulsed B cells were stimulated with other agents, such as dibutyryl cAMP and cholera toxin, that elevate intracellular levels of cAMP. In addition, RpcAMP, the R-isomer of a sulfur-modified cAMP and a cAMP antagonist, inhibited anti-FL IgG2a responses. The ability of cAMP elevators such as PGE2 to promote IgG2a production, as well as to increase the frequency of IgG2a secreting cells, was demonstrated in B lymphocytes treated with IFN-gamma and polyclonally activated by LPS. Overall, our results demonstrate that IFN-gamma and PGE2-treated B lymphocytes challenged with antigen or LPS generate elevated levels of IgG2a via a cAMP-dependent pathway. These observations suggest that in vivo, PGE2 secreted by cells such as macrophages potentiates the ability of IFN-gamma to promote an IgG2a response, the predominant murine antiviral Ig.

Animals↗
PubMed1991

Elevated levels of intracellular cAMP sensitize resting B lymphocytes to immune complex-induced unresponsiveness.

The ability of immune complexes (IC) to regulate B lymphocyte differentiation was investigated. Using an in vitro model, we previously demonstrated that macrophages (M phi) or lymphoid dendritic cells pulsed with IC differentially regulated B cell function, inducing unresponsiveness or stimulation, respectively. The capacity of M phi to induce unresponsiveness was dependent upon two signals, an antigen-specific one supplied by the IC and M phi-secreted prostaglandin (PG)E2. Total inhibition of antibody production was never achieved as a small percentage of B lymphocytes were resistant to IC-induced unresponsiveness. In this study, utilizing an accessory cell-free system, we demonstrate that splenic B cell fractions separated on Percoll density gradients are heterogeneous in their sensitivity to IC-mediated unresponsiveness. Small resting B lymphocytes are exquisitely sensitive to IC-mediated negative signaling and exhibit virtual total ablation of antibody responses. Conversely, large activated B cells are more refractory to this inhibitory pathway. PGE2 and other agents which elevate cAMP potentiate IC-induced unresponsiveness in resting, but not activated B lymphocytes. In addition treatment of resting B cells with PGF2 alpha, which did not elevate cAMP, failed to sensitize these cells to IC-mediated negative signaling. Unresponsiveness induced by IC is selective for specific aspects of B lymphocyte activation, since B cell differentiation but not proliferation is affected. Furthermore, pre-treatment of resting B lymphocytes with interleukin 4 prevents the IC-induced ablation of IgM antibody responses. Overall, our results indicate that the binding of IC by resting B lymphocytes provides a potent mechanism for inhibiting differentiation without affecting proliferation. These observations suggest that in vivo, IC play an important role in regulating the memory B lymphocyte pathway.

Animals↗
PubMed1991

A new view of prostaglandin E regulation of the immune response.

Prostaglandins, particularly those of the E series, are widely regarded as immunosuppressive products of eukaryotic cells that can downregulate many aspects of B- and T-cell function. In this article, Richard Phipps and colleagues present a different concept of E series prostaglandins, based on recent evidence supporting a role for prostaglandins as potentiators of immunoglobulin class switching and of the synthesis of selected cytokines and cytokine receptors.

Animals↗
PubMed1991

Amphotericin B selectively stimulates macrophages from high responder mouse strains.

Lymphoid cells from most inbred mouse strains respond to amphotericin B (AmB)-induced immunostimulation. However, C57BL/6 mice and related strains display low or absent lymphoid cell stimulation by AmB and enhanced susceptibility to AmB toxicity. Experiments reported here show that in vitro incubation with AmB can stimulate AKR (AmB-high responder strain) macrophage proliferation. Intraperitoneal injection of AKR mice with AmB also elicits a population of macrophages primed for enhanced oxidative burst activity after triggering by zymosan particles. Under the same experimental conditions, AmB elicits a population of very weakly responsive macrophages from C57BL/6 mice. The low responsiveness of C57BL/6 macrophages correlates with previous observations that AmB is a potent immunoadjuvant and B cell mitogen in most inbred strains, but it selectively lacks immunoadjuvant effects in C57BL/6 mice and it also fails to induce polyclonal B cell stimulation in their spleen cell suspensions. Similarly, in measurements of protein synthesis in vitro, high concentrations of AmB produce a greater inhibition of protein synthesis in C57BL/6 peritoneal macrophages than in parallel cultures of AKR macrophages. These findings support the hypothesis that the macrophage is an important target cell in the mediation of AmB-induced immunomodulation.

Amphotericin B↗
PubMed1990

Macrophage-secreted prostaglandin E2 potentiates immune complex-induced B cell unresponsiveness.

Immune complexes (IC) are potent modulators of immune responses. In this report, we used an in vitro murine model system to investigate how two types of accessory cells pulsed with IC regulated B cell function. We demonstrate that IC-pulsed macrophages (M phi) induce hapten-specific B cell unresponsiveness, whereas IC-pulsed splenic lymphoid dendritic cells (LDC) and and LDC-like tumor line caused an augmentation of the antibody response. The mechanism by which IC-pulsed M phi diminished antibody production required two signals. The first was an antigen-specific signal supplied by the IC, and the second a nonspecific co-factor which was a product of M phi cyclo-oxygenase metabolism. Specifically, it was shown that prostaglandin E2 (PGE2) could function at this co-factor. Interestingly, other prostanoids, such as PGF2 alpha, did not function in this fashion. Purified fluorescein (FL+)-specific B cells pulsed with IC exhibited a similar pattern of hapten-specific unresponsiveness. Treatment of accessory cell-free, FL+B cells with PGE2 rendered them sensitive to subtolerogenic doses of soluble IC. Overall, our results suggest that one mechanism by which unresponsiveness can be induced involves both IC and PGE2, and that elevated levels of PGE2 sensitize B lymphocytes to antigen-specific tolerogenic signals.

Animals↗
PubMed1990

Regulation of B-cell tolerance and triggering by macrophages and lymphoid dendritic cells.

This review explores the concept that accessory cells differentially regulate immune responses such that tolerance or immunity is induced. Macrophages and lymphoid dendritic cells differentially present hapten-conjugated Ig, antigen-antibody complexes and hapten-modified self such that hapten-specific B-cell development into IgM-secreting cells is blocked or stimulated. The mechanism by which macrophages inhibit B-lymphocyte differentiation is dependent upon an antigen-specific signal and a second nonspecific signal supplied by macrophage-derived E-series PG. In contrast, non PGE-producing lymphoid dendritic cells promoted maturation to IgM PFC by acting as a powerful stimulator of T-lymphocyte IL-2 production. PGE2, but not the structurally similar compound PGF2 alpha, synergized with ligands (e.g. antigen-antibody complexes) which cross-link B-cell sIg or both sIg and Fc receptors to promote hapten-specific unresponsiveness to thymus-independent antigens. Murine B lymphomas were also tested for sensitivity to E- and F-series PG. These cells varied in sensitivity to PGE2 and PGE1 in terms of growth inhibition, suggesting heterogeneity in B-cell PG responsiveness. Interestingly, E-series PG synergized with anti-Ig reagents to kill B lymphomas representative of "immature" normal B cells. In contrast to the effects of PGE on IgM production, we discovered that E-, but not F-series, PG promoted B-cell isotype switching to IgE and IgG1 in the presence of IL-4 and the polyclonal B-cell activator LPS. Other agents which stimulate a cAMP response also promoted isotype switching. These observations indicate that PGE are not obligatory inhibitors of immune responses. Research is in progress to uncover the molecular mechanisms by which PGE are "positive" or "negative" regulators of B lymphocytes.

Animals↗
PubMed1987

Parallel inheritance of tissue catalase activity and immunostimulatory action of amphotericin B in inbred mouse strains.

Both amphotericin B (AmB) and its methyl ester derivative are potent immunoadjuvants that also stimulate murine B lymphocytes and macrophages in vitro. Most of the common inbred mouse strains show AmB-induced immunostimulation (AmB-high responders) but mice from the C57BL strains, regardless of H-2 genotype, are AmB-low responders. Lymphoid cells from AmB-high responder strains also exhibit greater resistance to H2O2 toxicity in vitro compared with cells from AmB-low responders. This result led to an evaluation of differences in the tissue catalase levels of AmB-high and -low responder strains. Results from several laboratories, including ours, indicate that C57BL mouse strains express low levels of tissue catalase activity in addition to low or absent immunostimulant effects of AmB. Several AmB-high responder strains have high spleen cell, macrophage, and liver catalase, and the mouse strain distribution of enzyme activity as well as the dominant inheritance of the low catalase phenotype is compatible with regulation by the Ce-1 locus in lymphoid organs as well as liver. Other evidence also suggests that H2O2 metabolism is important in lymphoid cell responses to AmB. For example, AmB stimulates a stronger respiratory burst in macrophages from AmB-high responder strains under the same conditions that inhibit burst activity in macrophages from low responders. Selective immune enhancement by AmB in high catalase mouse strains along with enhanced susceptibility to AmB toxicity in low responder C57BL mice with low tissue catalase activity suggests that cellular peroxidation is a major determinant of the genetic regulation of amphotericin-induced immunostimulation.

Amphotericin B↗
PubMed1986

Myelolipoma arising from ectopic adrenal cortex: case report and review of the literature.

A myelolipoma was surgically removed following its identification by computed tomography scan. The presenting symptom was abdominal pain, associated with an enlarging mass in the lower abdomen. Histological review found the myelolipoma to be arising from ectopic adrenocortical tissue. Myelolipomas arising from extra-adrenal locations are rare. The literature was reviewed and various presentations of this benign tumor were discussed.

Abdominal Neoplasms↗
PubMed1985

Sequential methotrexate and 5-fluorouracil in the primary treatment of metastatic colorectal carcinoma.

Thirty-three patients with metastatic colorectal carcinoma were treated with sequential conventional dose methotrexate (60 mg/m2) followed within 1 hour by 5-fluorouracil (1000 mg/m2) every 3 weeks. Thirty of 33 patients were assessable for response. One patient (3%) achieved a partial remission (3.5 months). Three patients demonstrated minor tumor regressions. In an additional 17 patients, tumor stabilization was observed. The treatments were tolerated without any significant morbidity. A disappointingly low response rate was observed in our study as opposed to previous reports. Further clinical studies are necessary to establish the optimum dose levels and scheduling of sequential methotrexate and 5-fluorouracil.

Adult↗