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Biomedical subjects

S H Pincus

Publications and source records attributed to S H Pincus.

At least 109 records · Page 6Linked to original sources
PubMed1982

Monoclonal anti-(T,G)-A--L antibodies: characterization of fine specificity and idiotype expression.

The technique of polyethylene glycol mediated cell fusion was used to establish 22 monoclonal cell lines secreting anti-(T,G)-A--L antibody. Cell lines were derived from C3H.SW and B10 mice and produced antibody with kappa light chains and predominantly gamma 1, heavy chains. Fine-specificity analysis demonstrated that 15 cell lines made antibodies that also recognize a determinant present on GAT, GT (9:1) and GT (1:1), whereas little, if any, serum antibody demonstrates this cross-reaction. Fourteen antibodies, derived from both B10 and C3H.SW mice, bear idiotypic determinants defined by Lewis anti-[B10 anti-(T,G)-A--L], but only two, both from C3H.SW mice, react with Lewis anti-[C3H.SW anti-(T,G)-A--L]. Adsorption studies indicate that no hybridoma tested bore the complete set of idiotypic determinants defined by either serum.

Animals↗
PubMed1982

Superoxide production by eosinophils: activation by histamine.

Both guinea pig peritoneal exudate and human peripheral blood eosinophils produce large amounts of superoxide anion when stimulated by preopsonized zymosan or phorbol myristate acetate (PMA). Superoxide production is also activated by histamine but not the histamine metabolite, imidazole acetic acid. Supernatants from degranulated rat mast cells stimulate superoxide production. In studies of both human and guinea pig eosinophils, the H1-antagonist, chlorpheniramine (10-3 M and 10-4 M), preopsonized zymosan histamine) production of superoxide anion but the H2-antagonist, cimetidine, only modestly inhibited superoxide anion production (zymosan, PMA), These studies provide direct evidence for the influence of histamine on the oxidative metabolism of eosinophils. These results are consistent with the hypothesis that histamine interacts with eosinophils predominantly via an H1 receptor site. Furthermore, they suggest that eosinophils may participate in immediate hypersensitivity reactions by the release of superoxide anion in response to stimulation by histamine.

Animals↗
PubMed1982

Idiotypic analysis of hybridoma antibodies to branched synthetic polymer (Tyr, Glu)-Ala-Lys: idiotypic relationship with antibodies to linear random polymer (Glu60, Ala30, Tyr10).

The expression of three anti-GAT idiotypes, CGAT, Gte, and GA-1, on 17 C57BL/10 and four C3H.SW hybridoma anti-(T,G)-A--L antibodies was analyzed. These hybridoma anti-(T,G)-A--L antibodies exhibited two patterns of fine antigen binding specificity. The majority of the hybridoma antibodies bound the (T,G)-A--L, GT, and GAT polymers but not the GA polymer, and were designated as GT-reactive hybridoma antibodies. A minor population of hybridoma anti(T,G)-A--L antibodies bound to (T,G)-A--L but not to GT, GAT, or GA, i.e., (T,G)-A--L-specific. A complete correlation between fine antigen binding pattern and the expression of CGAT idiotype was demonstrated. None of the 21 hybridoma anti-(T,G)-A--L antibodies expressed the GA-1 idiotype. All of the GT-reactive and none of the GT-nonreactive hybridoma anti-(%,G)-A--L antibodies expressed the CGAT idiotype. Furthermore, the Gte idiotype was found on the majority of CGAT+-bearing C57BL/10 hybridoma anti-(T,G)-A--L antibodies. These results indicate that C57BL/10 anti-(T,G)-A--L antibody repertoire can be grouped into a minimum of three families; i.e., CGAT+ Gte+, CGAT+ Gte-, and CGAT- Gte- families, with the CGAT+ Gte+ family as the major compartment. This is confirmed by the high percentage idiotype binding of serum anti-(T,G)-A--L antibodies with anti-CGAT idiotypic antisera. Finally, anti-idiotypic antisera made against CGAT+ hybridoma anti-GAT or anti-(T,G)-A--L antibodies crossreact extensively with other CGAT+ hybridoma anti-GAT and anti-(T,G)-A--L antibodies. However, additional experiments demonstrated that CGAT+ hybridoma anti-(T,G)-A--L antibodies also possess private idiotypes.

Animals↗
PubMed1981

Cutaneous necrosis caused by systemically administered heparin.

Two cases of cutaneous necrosis occurred that were caused by intravenous administration of porcine heparin for deep venous thrombophlebitis. The lesions grossly resembled those of warfarin sodium-induced skin necrosis. However, histologically, no fibrin thrombi were noted in capillaries and vessels, a characteristic finding in warfarin necrosis. There was no evidence of vasculitis in the lesions. Both patients subsequently received warfarin without complications.

Adult↗
PubMed1981

Metabolic heterogeneity of eosinophils from normal and hypereosinophilic patients.

Eosinophils, which may be associated with allergic, parasitic, or neoplastic disease, have a potent oxidative burst that may be activated by particulate or soluble stimuli. Eosinophils from normal persons and patients with hypereosinophilia were compared with respect to their ability to produce the active oxygen product, superoxide anion. Normal eosinophils produced large amounts of superoxide anion under resting conditions (0.53 +/- 0.15 nmoles cyto-c/10(5) eos/hr) and when stimulated by preopsonized zymosan (0.85 +/0 1.10 nmoles cyto-c/10(5) eos/hr) or phorbol myristate acetate (PMA) (2.38 +/- 0.46 nmoles cyto-c/10(5) eos/hr). Considerable variation was observed in superoxide production by eosinophils from patients with hypereosinophilia. Eosinophils from a group of four patients with hypereosinophilia associated with neoplastic disease produced less superoxide anion than normal eosinophils when stimulated by preopsonized zymosan or PMA (p less than or equal to 0.05). Eosinophils from a group of 5 patients with other causes of hypereosinophilia produced more superoxide anion than normal eosinophils when stimulated by PMA (p less than or equal to 0.01). These studies demonstrate metabolic heterogeneity of eosinophils from patients with hypereosinophilia, and further emphasize that normal eosinophils and eosinophils from hypereosinophilic patients are not functionally equivalent.

Eosinophilia↗
PubMed1980

Peroxidase-mediated iodination by guinea pig peritoneal exudate eosinophils.

Leukocyte iodination, which requires the granular enzyme perioxidase, hydrogen peroxide generated by the cell, and an appropriate oxidizable cofactor such as iodide, was studied in guinea pig peritoneal exudates. Eosinophils had an active resting iodination which was increased approximately 10-fold by the addition of serum and zymosan. In contrast, neutrophils had barely detectable resting iodination, but marked stimulation also occurred employing serum and zymosan or preopsonized zymosan. Under all conditions tested eosinophil iodination was significantly greater than neutrophil iodination (P less than 0.001). The role of the peroxidase system in iodination was confirmed by inhibition in the presence of 10(-3) M azide, cyanide, or aminotriazole. Inhibition by exogenous catalase and facilitation by superoxide dismutase substantiated the role of hydrogen peroxide. Autoradiographic and cell separation studies confirmed that the majority of iodination was cell or particle associated.

Animals↗
PubMed1978

Production of eosinophil-rich guinea pig peritoneal exudates.

A variety of methods for production of eosinophil-rich guinea pig peritoneal exudates were tested in order to procure large numbers of purified eosinophils. Repeated peritoneal lavage with saline did not produce peritoneal eosinophilia, nor did intraperitoneal injection of dextran beads. Mast cell degranulating agents polymyxin B and, to a lesser degree, compound 48/80 produced significant peritoneal eosinophilia after 6-8 wk of weekly intraperitoneal injections (p less than or equal to 0.05). After more than 8 wk of treatment a mean of 52.1 x 10(6) eosinophils comprising an average of 62% of the peritoneal exudate cells was recovered from polymyxin B-treated guinea pigs. However, polymyxin B-induced peritoneal eosinophilia was abolished by pretreatment with the antihistamine diphenhydramine. Metiamide, an H2 receptor antagonist, did not block the production of peritoneal eosinophils. This is a highly satisfactory method for preparing peritoneal eosinophils; however, the mechanism of action remains to be clearly elucidated.

Animals↗
PubMed1978

Production of antisera specific for idiotype(s) of murine anti-(T,G)-A--L antibodies.

Antibodies to the synthetic polypeptide (T,G)-A--L were raised in C57BL/10 and C3H.SW mice. For each strain, the anti-(T,G)-A--L antibodies from 10 animals were pooled, affinity purified on a (T,G)-A--L-Sepharose column, and used to immunize Lewis rats. The resulting rat antisera were adsorbed with insolubilized normal mouse globulin in order to remove anti-isotypic and anti-allotypic antibodies. The residual antibodies specifically inhibited the binding of (T,G)-A--L by anti-(T,G)-A--L as measured by a radioimmunoassay. The specificity of this inhibition was demonstrated as follows: 1) failure of the anti-(T,G)-A--L anti-idiotype to inhibit the binding of nuclease to anti-nuclease antibody of the same allotype; 2) failure of Lewis anti-[B10 anti-(T,G)-A--L] to inhibit C3H.SW anti-(T,G)-A--L and vice versa; 3) ability to absorb anti-C3H.SW anti-idiotypic activity on insolubilized C3H.SW anti-(T,G)-A--L but not on B10 anti-(T,G)-A--L. The same or cross-reactive idiotype(s) was present in the majority of individuals of each of these strains.

Animals↗
PubMed1978

A subpopulation of adherent accessory cells bearing both I-A and I-E or C subregion antigens is required for antigen-specific murine T lymphocyte proliferation.

A murine T lymphocyte proliferation assay that used antigen-primed lymph node T cells, was antigen specific, and required exogenous accessory cells was used to characterize the accessory cells that supported proliferation. These cells were Thy 1.2 negative, radioresistant, glass-adherent, and were functional only if alive. The accessory cell function of spleen adherent cells was much greater than that of peritoneal cells. Also, the accessory cell function of spleen adherent cells was proportional to the length of time such cells were incubated with antigen and very small numbers of such cells provided accessory cell function. Cytotoxic studies with subregion-restricted anti-Ia antibodies and complement indicated that accessory cell function resided in a subpopulation of spleen adherent cells that bore both I-A and I-E or C subregion antigens. The function of such cells was not related to a selective ability (vs other spleen adherent cells) to take up antigen. These data indicate that antigen-specific stimulation of T lymphocyte proliferation requires at least one specific subpopulation of spleen adherent cells that can be phenotypically identified by its expression of Ia antigens and are consistent with the possibility that Ia antigens may be Ir gene products.

Animals↗
PubMed1977

Increase in titer of the naturally occurring human antibody to neuraminidase-treated lymphocytes after influenza.

Nine of 25 (36%) humans suffering from naturally acquired influenza A infection developed significant increases in the titer of a "naturally" occurring antibody to neuraminidase-treated human lymphocytes. Only two of 43 normal and noninfluenza respiratory infection controls showed titer changes of this antibody, p less than 0.001. The antibody was not directed at influenza virus C fixation, hemagglutination inhibition, or neuraminidase antigens. Three of 10 normals given a highly immunogenic, formalin-killed influenza A vaccine developed significant titer rises. These results suggest that influenza virus, live or dead, can provoke an increase in antibody to a cross-reacting antigen present on neuraminidase-treated human lymphocytes.

Adolescent↗
PubMed1976

Chronic neutropenia in childhood. Analysis of 16 cases and a review of the literature.

We analyzed the clinical histories and hematologic information concerning 16 persons in whom chronic neutropenia was discovered early in life. Only two of them, those with the lowest mean neutrophil counts, had frequent and severe pyogenic infections. Almost all the infections were caused by Staphylococcus aureus or by enteric microorganisms and involved the skin, respiratory tract or gastrointestinal system. The prognosis in our subjects or in patients described in the literature could not be predicted from the bone marrow morphology, presence or absence of blood monocytosis, pattern of genetic transmission or results of special tests of neutrophil function. We propose that the complex nomenclature associated with chronic neutropenic states be discarded until a better basis for classification becomes available.

Adolescent↗
PubMed1975

Defective neutrophil chemotaxis with variant ichthyosis, hyperimmunoglobulinemia E, and recurrent infections.

Host defense mechanisms were evaluated in a 4-1/2-year-old boy with recurrent pyogenic infections and a unique hyperkeratotic skin disorder. The patient's neutrophils were consistently defective in chemotactic responsiveness but had normal NBT reduction, glucose oxidation, and iodination. Serum concentrations of IgE were markedly elevated and the secondary antibody response was abnormal. No T-cell dysfunction was detected. These findings suggest a relationship between this patient and patients with other syndromes associated with recurrent infections, cutaneous disease, defective chemotaxis, immunodeficiency, and hyperimmunoglobulinemia E.

Chemotaxis↗
PubMed1971

Hydrogen peroxide utilization in myeloperoxidase-deficient leukocytes: a possible microbicidal control mechanism.

Phagocytosis-induced formate and glucose C-1 oxidation by the polymorphonuclear leukocytes of a patient with hereditary myeloperoxidase deficiency was considerably greater than normal. The addition of catalase to the leukocyte suspension was required for optimum formate oxidation. Azide and cyanide increased glucose C-1 oxidation by normal leukocytes but had little or no effect on myeloperoxidase-deficient leukocytes suggesting that these agents normally stimulate glucose C-1 oxidation, in part, by inhibition of myeloperoxidase. It is suggested that the inhibition or absence of myeloperoxidase results in an increased utilization of H(2)O(2) in nonmyeloperoxidase-mediated H(2)O(2)-dependent reactions such as formate oxidation and hexose monophosphate pathway activation. The possibility of a microbicidal control mechanism in which a decrease in the microbicidal activity of myeloperoxidase is offset, in part, by an increase in the nonenzymatic microbicidal activity of H(2)O(2) is considered.

Azides↗