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Biomedical subjects

S H Pincus

Publications and source records attributed to S H Pincus.

At least 91 records · Page 5Linked to original sources
PubMed1986

Eosinophilia in murine trichinellosis.

In both primary and secondary infections using 3 different strains of mice (DBA/1, B10 X D2, and C3H/HeJ), 2 peaks of peripheral blood eosinophilia were noted. Depending upon the strain, the first of the biphasic peaks in primary infections occurred between days 5 and 9, and the second peak occurred between days 16 and 22. The relative heights of the peak varied with the strain. In secondary infections, the initial peak was lower and the larger second peak occurred earlier. Methyridine treatment to eliminate adults prior to release of newborn larvae altered neither the course of eosinophilia in primary infection nor the biphasic distribution of eosinophilia. These studies demonstrate that the adult worm is responsible for inducing eosinophilia in murine infections, that 2 peaks of eosinophilia exist in primary and secondary infections, and that eosinophilia in secondary infections is an anamnestic response.

Animals↗
PubMed1985

Characterization of T cells bearing HLA-DR antigens in rheumatoid arthritis.

It has been demonstrated that T cells bearing HLA-DR antigens on their surface are actively involved in an immune response. In diseases of disordered immunoregulation, including rheumatoid arthritis (RA), there are elevated numbers of circulating HLA-DR+ T cells. In this study, we examined the cellular physiology of these T cells in RA patients. Using tritiated thymidine incorporation, we found that, in most patients, HLA-DR+ cells do not account for a significant amount of spontaneous proliferation found in peripheral blood T cells. RNA hybridization studies, using a cloned HLA-DR alpha chain gene probe, indicate that the T cells actively synthesize HLA-DR antigens rather than passively adsorbing them. The cell surface phenotype of the HLA-DR+ T cells was analyzed using double immunofluorescence and a variety of monoclonal antibodies. The expression of T cell differentiation antigens T4, T6, T8, and T10 varied markedly from patient to patient. In some patients, a significant number of cells expressed both T4 and T8 antigens. Most HLA-DR+ cells also express antigens defined by the following antibodies: anti-Tac (the interleukin-2 receptor), J2 (a glycoprotein found on T cell blasts), and ILR-1 (a class II major histocompatibility complex antigen). Activated T cells bearing HLA-DR antigens may play a role in the development of RA. Our data demonstrate that although these cells are not lymphoblasts, they possess a distinct cell surface phenotype.

Antigens, Surface↗
PubMed1985

Human lymphocyte-eosinophil interactions. I. Modulation of phytohemagglutinin-induced lymphocyte proliferation by eosinophils.

Do eosinophils modulate lymphocyte function? This question was studied by examining the effect of purified eosinophils (eos) on lectin-induced human lymphocyte proliferation. Intact resting or zymosan-stimulated eos or their extracts were cocultured with phytohemagglutinin-stimulated mononuclear cells in vitro and [3H]thymidine uptake was measured at 72 hr. Zymosan-stimulated eos consistently suppressed (up to 90%) the lectin-induced proliferative response by a noncytotoxic mechanism. Freeze-thaw extracts from zymosan-stimulated eos also significantly suppressed lymphocyte proliferation to a similar degree. The amount of suppression was directly proportional to the number of eos or the amount of extract added to the lymphocyte cultures. Intact resting eos and their extracts occasionally exhibited suppressive effects (up to 40%) on lymphocyte proliferation; this suppression, however, was always less than that of activated eos or their extracts. Eos pretreated with the protein synthesis inhibitor, pactamycin, exhibited significantly less suppressive activity, suggesting that a protein was responsible in part for the reduction in proliferation. The addition of superoxide dismutase or catalase to the eos-mononuclear cell cocultures did not reduce the amount of suppression observed, thus making it unlikely that active oxygen products were involved in the mechanism of suppression. Heating extracts from stimulated eos to 80 degrees C for 30 min resulted in partial loss of suppressive activity while extensive dialysis of the extracts had no effect. The studies reported here provide evidence that a nondialyzable and heat sensitive factor(s) produced by stimulated eos may exert feedback inhibition of lymphocyte function.

Catalase↗
PubMed1985

Variable regions of antibodies to synthetic polypeptides--I. Characterization of an idiotope expressed on antibodies and T-cell factors.

Spleen cells from a Lewis rat immunized with affinity-purified B10 anti-(T,G)-A-L antibody were fused with the non-secreting murine hybridoma SP2/0. Cell lines secreting monoclonal antibodies specific for mu- and kappa-chains, as well as an idiotope on anti-(T,G)-A-L antibodies, were isolated and characterized. The anti-mu and -kappa antibodies, are true anti-isotypes, reacting with sera from all strains of mice tested. The anti-idiotope antibodies recognize a determinant on antibodies binding a GT-containing epitope. The proportion of anti-GAT antibody bearing the idiotope varies markedly in different murine strains. A 1000-fold higher level of antibody from Igha mice than from Ighb and Ighe mice is required to give an equivalent inhibition of the idiotope-anti-idiotope reaction. Analysis of monoclonal antibodies expressing the idiotope indicates that the affinity of binding between idiotope and anti-idiotope can vary by as much as two orders of magnitude. Immunoadsorbants prepared with anti-idiotope antibody bind suppressor factor secreted by a GAT-specific T-cell hybridoma.

Animals↗
PubMed1985

Eosinophil adherence to infective larvae of Trichinella spiralis: quantification and modulation.

Eosinophils play an important role in host defence against helminthic infection. A quantitative system for studying the interactions of eosinophils and a large non-ingestible target was developed using infective muscle-stage larvae of Trichinella spiralis. At 37 degrees, this antibody-dependent system provided a reliable, reproducible index of eosinophil function. Adherence was equivalent under aerobic and anaerobic conditions. No significant differences were noted between peritoneal exudate eosinophils from Trichinella-infected and normal animals. Adherence was inhibited by leukotriene inhibitors [eicosaetraynoic acid (10(-3) M), nordihydroguaiaretic acid (10(-4) M), and BW755C (10(-3) M)] but not by prostaglandin inhibitors (aspirin and indomethacin), suggesting that leukotrienes mediate this eosinophil function. This assay provides another useful method for assessment of a crucial eosinophil function.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1984

Phenotypic and genotypic characterization of monoclonal anti-digoxin antibodies.

Eleven hybridoma cell lines secreting monoclonal anti-digoxin antibody have been produced. They are primarily gamma heavy chain and kappa light chain molecules. Affinity constants for digoxin range from 2 X 10(6) to 3.5 X 10(8) liters/mole. Fine specificity analysis using a series of digoxin congeners demonstrates that an unsaturated lactone ring attached to the aglycone at the C-17 position is necessary for hapten recognition. The impact of other changes in digoxin's structure on antibody binding were also studied. DNA hybridization analysis demonstrates that there are at least three different variable region gene arrangements used to produce the heavy chains of the different hybridoma antibodies. Correlations between antigen binding characteristics and antibody V-gene arrangements are demonstrable.

Animals↗
PubMed1984

Eosinophil-mediated killing of schistosomula of Schistosoma mansoni: oxidative requirement for enhancement by eosinophil colony stimulating factor (CSF-alpha) and supernatants with eosinophil cytotoxicity enhancing activity (E-CEA).

Factors which enhance eosinophil-mediated killing of antibody-coated schistosomula of Schistosoma mansoni include semipurified eosinophil colony stimulating factor (CSF-alpha) and eosinophil cytotoxicity enhancing activity (E-CEA) present in supernatants from cultured mononuclear cells. We have examined the mechanism of enhancement. Both actions require oxygen in order to enhance killing and do not enhance killing under anaerobic conditions (P less than or equal to 0.005). E-CEA had no detectable effect upon oxidative metabolism. In contrast to CSF-alpha which, in our previous studies, increased superoxide anion productions and quantitative leukocyte iodination, E-CEA had no detectable effect upon oxidative metabolism. In order to test whether active oxygen products might mediate enhancement of killing, the effects of the addition of superoxide dismutase and catalase were tested. Neither enzyme showed inhibition of CSF-alpha or E-CEA enhancement of eosinophil-mediated killing. The effects of CSF-alpha and E-CEA were not additive. These studies suggest that both CSF-alpha and E-CEA exert enhancement of killing by means of an as yet unidentified oxygen requiring process.

Animals↗
PubMed1984

Eosinophil-particle interactions: a model system for study of cellular adherence and activation.

In its role as an effector capable of killing large multicellular parasites, the eosinophil must be especially adapted for dealing with noningestible surfaces. A model system of Sepharose beads coated with serum protein or concanavalin A (Con A) has been used to study interactions between guinea pig peritoneal exudate eosinophils and noningestible particles. A small percentage of eosinophils were adherent to serum treated Sepharose; however, many cells were adherent to Con A-Sepharose. Adherence to Con A-Sepharose was decreased by pretreatment with 1 mM alpha-methylmannoside (alpha-MM). As compared to resting eosinophils, incubation of eosinophils with serum-treated Sepharose led to activation of oxidative metabolism as indicated by an eight-fold increase in superoxide anion production and an approximately threefold increase in quantitative leukocyte iodination. Eosinophils which were adherent to Con A beads could not be activated by either phorbol myristate acetate (PMA) or preopsonized zymosan. However, if adherence was reduced by preincubation with alpha-MM, PMA was able to activate the eosinophils. Neither soluble Con A nor Sepharose beads interfered with the assay of superoxide anion. These studies demonstrate the utility of Sepharose beads for studying interactions between eosinophils and noningestible particles.

Animals↗
PubMed1984

Protective efficacy of hybridoma type-specific antibody against experimental infection with group-B Streptococcus.

Murine monoclonal antibodies to group-B Streptococcus type III were developed by fusion of splenic lymphocytes from immunized BALB/c mice with the mouse-myeloma cell line SP 2/0. The four type III-specific antibodies, which were of the IgM class, protected neonatal rats against intraperitoneal infection with homologous-type group-B streptococci; survival rates were 95%-100% for protected rats but only 17% for unprotected rats. One antibody preparation offered excellent protection against any of five type-III strains employed. Monoclonal antibody provided protection when administered 4, 8, or 12 hr after infection, although delayed administration was less efficacious against more virulent strains. Monoclonal IgM also protected against intranasal inoculation of bacteria. These results indicate the potential therapeutic efficacy of monoclonal antibody in neonatal group-B streptococcal disease, but further laboratory investigations must precede clinical investigation of monoclonal or polyclonal antibody therapy in humans.

Animals↗
PubMed1984

Absolute requirement for complement in monoclonal IgM antibody-mediated protection against experimental infection with type III group B streptococci.

The role of complement in the protective and opsonic activity of monoclonal IgM antibody to type III group B streptococci (GBS) was examined in a neonatal rat model of infection and in vitro with human sera as the complement source. C3 levels in uninfected neonatal rats were less than 50% of those in adult rats, similar to the low complement levels observed in human neonates. The monoclonal type III-specific IgM antibody provided protection to neonatal rats (with unaltered complement levels) that were infected intra-peritoneally or intranasally with type III GBS. In contrast, neonatal rats depleted of complement by administration of cobra venom factor were not protected by IgM antibody. In vitro, classical complement pathway activity was adequate in sera from well, term neonates and GBS-infected neonates in the presence of higher concentrations of the monoclonal IgM antibody. At lower IgM levels, however, the alternative complement pathway was less efficient in both neonatal sera and adult sera.

Adult↗
PubMed1984

Anaphylaxis in mast cell-deficient mice.

Evidence of a functional deficit in mast cell-deficient mice was sought by testing for the development of systemic anaphylaxis. W/Wv mast cell-deficient mice and wild type control animals were sensitized by injection of bovine serum albumin and subsequently challenged. Nine of ten W/Wv mast cell-deficient mice and 10/10 control mice demonstrated signs of anaphylaxis, including death. Although histamine levels were higher in control animals, no differences were noted before and after antigen challenge. The numbers of peripheral blood basophils were the same in W/Wv and wild type mice. These studies suggest that caution is necessary in the use of these animals to study disease.

Anaphylaxis↗
PubMed1984

Treatment of experimental group B streptococcal infection with hybridoma antibody.

Previous studies have shown a reduction in mortality rate from 90% to zero when neonatal rats, inoculated with group B streptococci (GBS) were injected with type-specific IgM antibody. However, in those studies, the antibody was administered simultaneously with the bacteria and at the same site, unlike the situation which would exist if antibody was used clinically to treat established infection. In the present experiments, we administered antibody intraperitoneally at various intervals following intrathoracic inoculation of GBS. When antibody was administered immediately after, or up to 2 h following bacterial inoculation, all animals survived. When antibody administration was delayed for 4, 5, or 6 h, survival rates of 92, 60, and 29% were observed. When antibody administration was delayed for more than 6 h, no survival occurred. Failure of antibody to protect animals from death coincided temporally with profound depletion of the neutrophil storage pool. In other experiments, depletion of the neutrophil storage pool was produced by a separate, noninfectious mechanism (subcutaneous implantation of sterile polyvinyl sponge discs) after which animals were inoculated with GBS. Antibody did not provide protection from death in animals with neutrophil storage pool depletion.

Animals↗
PubMed1984

Inhibition of CFU-NM and CFU-EOS by mature granulocytes.

Approximately half of the colony-forming units-culture (CFU-C) from normal peripheral blood are eosinophilic. The purpose of our study was to determine: (1) whether progenitor cells committed to eosinophil or neutrophil maturation would be differentially affected by feedback inhibition, and (2) whether mature eosinophils added to the feeder layers of the culture would inhibit the proliferation of CFU-C in a manner similar to that described for neutrophils. Concentrated eosinophils and neutrophils, obtained by separation on a metrizamide gradient, were added to feeder layers containing either 10(6) autologous whole mononuclear cells (WMNC) or 0.1 ml of leukocyte conditioned media (LCM). The average number of colonies was 123/10(6) nonadherent cells (NAC) cultured. When neutrophils or eosinophils were added to the WMNC feeder layer, the percent inhibition of growth was 40.2% +/- 1.6% (mean +/- SEM) and 42.3% +/- 5.4%, respectively, but the ratio of neutrophil to eosinophil colonies remained constant. No effect was seen when neutrophils or eosinophils were added to an LCM feeder layer. Thus, it appears that the differential control of neutrophil versus eosinophil production in vitro is not regulated through feedback inhibition by mature granulocytes. In addition, these studies suggest that eosinophils, as well as neutrophils, cause inhibition of CFU-C growth when intact cells are the source of colony-stimulating factor (CSF).

Colony-Forming Units Assay↗
PubMed1984

Immunoselection of B cell hybridomas with anti-idiotypic antisera to study the role of heavy and light chains for idiotype expression and antibody activity.

Conventional reconstitution experiments with heavy (H) and light (L) offins of hybridoma anti-poly-(Glu60Ala30Tyr10) (anti-GAT) antibodies demonstrated that H and L chains are required for efficient expression of anti-GAT activity and the previously defined common CGAT idiotype. On the basis of this observation, we treated a CGAT+ hybridoma cell line (F9.195.6), which was produced by fusion with an MOPC 21 (gamma 1, K) secretor line, with anti-CGAT idiotypic antibodies plus complement to select CGAT-variants. Such treatment greatly enhanced the frequency of isolating hybridoma variants. Molecules secreted from these variants bear anti-GAT mu-chain and MOPC 21 L chain (as judged by serology and Southern blot studies), lack GAT binding activity and CGAT idiotype, and exhibit a "new" private idiotype (E8). Anti-private idiotypic sera were successfully used to select a series of CGAT+, E8- clones that secrete molecules bearing only the appropriate anti-GAT mu- and K chains. From E8- hybridoma supernatants, CGAT- molecules bearing MOPC 21 H chain and anti-GAT L chain could be obtained. The data indicate that immunoselection of hybridoma clones with anti-idiotypic antibodies is a convenient means of preparing reconstituted antibody molecules. Furthermore, the data demonstrate that CGAT idiotype determinants are expressed on antibody molecules composed of appropriate H and L chains.

Animals↗
PubMed1983

A somaticizing adolescent: an approach to evaluation and therapy.

Adolescents may chronically somatize as part of the symptoms of an underlying psychological disorder. Unless the underlying psychological disorder. Unless the underlying psychopathology is recognized by the treating physician, chronic somatization may result in high cost to the health care system due to frequent use and unnecessary biochemical and radiographic evaluation. The case presented is illustrative of the differential diagnosis and management of such a patient.

Adolescent↗
PubMed1983

Hydrogen peroxide release from eosinophils: quantitative, comparative studies of human and guinea pig eosinophils.

Eosinophils play an important role in host defense against parasitic infection, employing both oxidative and nonoxidative systems to effect damage. The active oxygen product, hydrogen peroxide, either alone or in combination with the enzyme eosinophil peroxidase, may damage parasites. These studies use a sensitive fluorometric assay to document the release of hydrogen peroxide from guinea pig peritoneal exudate eosinophils and human peripheral blood eosinophils. Guinea pig eosinophils released 0.13 +/- 0.02 (n = 10) nmol H2O2/10(5) eos/5 min under resting conditions which were markedly increased when stimulated by phorbal myristate acetate (PMA, 1 microgram/ml) [4.80 +/- 0.50 (19) nmol H2O2/10(5) eos/5 min], preopsonized zymosan [2.40 +/- 0.17 (4) nmol H2O2/10(5) eos/5 min], or latex beads [1.14 +/- 0.26 (5) nmol H2O2/10(5) eos/5 min]. Normal human peripheral blood eosinophils had greater resting release of hydrogen peroxide [0.34 +/- 0.05 (8) nmol H2O2/10(5) eos/5 min], but were less effectively stimulated by PMA [3.12 +/- 0.57 (9) nmol H2O2/10(5) eos/5 min], preopsonized zymosan [0.78 +/- 0.16 (8) nmol H2O2/10(5) eos/5 min] or latex beads [0.69 +/- 0.32 (6) nmol H2O2/10(5) eos] (p less than or equal to 0.05). Hydrogen peroxide release was markedly enhanced by the presence of exogenous glucose and was linearly dependent upon cell number when the soluble stimulus PMA was used. Particle-stimulated hydrogen peroxide was not necessarily enhanced by increases in the particle:cell ratio. The demonstration of the release of large amounts of hydrogen peroxide from eosinophils is further support for the concept that eosinophils play an active role in host defense.

Animals↗
PubMed1983

The effect of hybridoma antibody administration upon neutrophil kinetics during experimental type III group B streptococcal sepsis.

Groups of newborn rats were transthoracically inoculated with 1 X 10(6) type III group B streptococci/g body wt, either alone or in combination with 1.5 microgram/g body wt of type-specific antibody derived from hybridoma cell lines. Ninety-four percent of the animals who received bacteria alone died. In contrast, none of those treated with antibody died (P less than 0.005). Kinetic studies suggested that antibody may have offered protection, In part, by facilitating the neutrophil response. Animals who received only bacteria exhibited a marked neutropenia (20 +/- 18/mm3, mean +/- S.E.M.) whereas infected animals treated with antibody did not (3800 +/- 30/mm3, P less than 0.001). Furthermore, within 2 h of inoculation, antibody-treated animals mobilized and stored neutrophils, whereas significant neutrophil mobilization did not occur in the animals which received bacteria alone until 6 h. In the animals receiving bacteria alone, exhaustion of the neutrophil supply quickly occurred (remaining storage neutrophils at 6 h, 0.2 +/- 0.1 X 10(6) cells). In contrast, animals, which received antibody, maintained an adequate supply of stored neutrophils (7.0 +/- 0.4 X 10(6) P less than 0.001). The migration of neutrophils to the site of inoculation was measured by assaying the lungs' content of myeloperoxidase, a marker enzyme for granulocytes. The right and left lungs of animals not receiving antibody accumulated the same quantity of neutrophils, with peak pulmonary neutrophil accumulation occurring 6 h after the infection. In antibody recipients, however, the inoculated lung accumulated significantly more neutrophils than the opposite lung and peak pulmonary neutrophil accumulation occurred at 2 rather than 6 h.

Animals↗