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Biomedical subjects

J R Wands

Publications and source records attributed to J R Wands.

At least 235 records · Page 13Linked to original sources
PubMed1976

Mechanism of human lymphocyte stimulation by concanavalin A: role of valence and surface binding sites.

A monovalent form of concanavalin A (m-Con A) has been prepared to determine the importance of valence for human lymphocyte surface binding and subsequent lymphocyte stimulation as measured by blast transformation and cytotoxicity. Concanavalin A (Con A) was fragmented by a proteolytic process and the m-Con A) derivative was isolated by elution with an ascending D-glucose gradient on a Sephadex G-200 column. The molecular weight of m-Con A was 18,000 by sodium dodecyl sulfate-polyacrylamide electrophoresis. Equilibrium dialysis with alpha-methyl D-glucoside and subsequent Scatchard plot analysis revealed an association constant (Ka) of 1.2 X 10(3) liters/mol and a valence of 1.1. Incubation of lymphocytes with 125I-labeled m-Con A demonstrated surface binding at 1.21 X 10(6) molecules per cell, which was comparable to the binding of [3H] Con A (1.02 X 10(6) molecules per cell). However, in contrast to the intact lectin, m-Con A had a markedly reduced capacity to agglutinate rabbit erythrocytes and human lymphocytes and did not stimulate lymphocyte blast transformation or cytotoxicity at 1 and 10 mug/ml. Finally, pretreatment of lymphocytes with m-Con A blocked blast transformation induced by Con A. These observations demonstrate that m-Con A binds to lymphocyte surface receptors but does not stimulate blast transformation or cytotoxicity, suggesting that Con A must bridge binding sites on the lymphocyte surface to induce lymphocyte activation.

Binding Sites↗
PubMed1976

Cryoprotein complexes and peripheral neuropathy in a patient with chronic active hepatitis.

A cryoprotein complex was isolated and characterized from a patient with chronic active hepatitis and a severe peripheral neuropathy. This cryoprotein was composed of IgM, IgG, and hepatitis B surface antigen (HBsAg) and had a concentration of approximately 36 mg per 100 ml of serum. Electron microscopic examination of the cryoprotein demonstrated aggregates of Dane particles in close association with the antigenically related tubular and spherical forms of HBsAg. HBsAg, IgM, and IgG were detected by immunofluorescent staining in the intima of small arteries and veins. The association of a high serum level of cryoprotein and deposition of the cryoprotein components in small blood vessels suggests a role for the cryoprotein in the pathogenesis of peripheral neuropathy in this patient with chronic active hepatitis.

Antigen-Antibody Complex↗
PubMed1975

Cell-mediated immunity in acute and chronic hepatitis.

Peripheral lymphocytes from patients with hepatitis-B surface antigen (HBsAg)-positive and -negative acute hepatitis (AH), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and normal controls were tested for in vitro cytotoxicity and blast transformation. Cytotoxicity was measured by chrominum (21Cr) release into the medium from 51Cr-labeled Chang liver cells after incubation for 6 h with peripheral lymphocytes at a lymphocyte target cell ratio of 200:1. Concomitant 72-h incubation studies were performed to assess thymus cell-dependent (T) lymphocyte function as measured by conccanavalin A (Con A)- stimulated incorporation of tritiated thymidine (blast transformation) and by cytotoxicity. It was found that (a) lymphocytes from patients with AH are cytotoxic to Chang liver cells compared to controls (P less than 0.001); (b) lymphocytes from patients with acute and chronic hepatitis are less cytotoxic when incubated with autologous and homologous HB2Ag-positive and -negative AH, CAH, and CPH are as cytotoxic as normal controls when stimulated with a nonspecific mitogen such as Con A; and (d) lymphocytes from patients with CAH while on prednisone therapy showed marked depression of cytotoxicity when stimulated with Con A. Thus these studies show that patients with AH have circulating T lymphocytes which are capable of causing the destruction of Chang liver cells. There is no defect in T-cell function as measured by Con A-stimulated cytotoxicity. There is a serum factor (s) in patients with acute and chronic hepatitis which inhibits spontaneous and induced lymphocyte cytotoxicity and blast transformation. Finally, prednisone treatment appears to inhibit lymphocyte cytotoxicity in patients with CAH.

Acute Disease↗
PubMed1975

The pathogenesis of arthritis associated with acute hepatitis-B surface antigen-positive hepatitis. Complement activation and characterization of circulating immune complexes.

Circulating immune complexes were identified in cryoproteins isolated from serial samples of serum from six patients with acute viral hepatitis with and without arthritic symptoms. Cryoprecipitates were analyzed for the presence of hepatitis-B surface antigen (HBsAg) and hepatitis-B surface antibody (anti-HBs) by hemagglutination inhibition and hemagglutination. Complement components were detected by counter electrophoresis, and immunoglobulins were detected by gel diffusion. HBsAg, IgG, and IgM were identified in cryoprecipitates from all hepatitis patients, but were higher in concentration in patients with arthritis. Only cryoprecipitates from hepatitis patients with arthritis contained IgA and complement components C3, C4, and C5 as well as IgG and IgM, which disappear with resolution of the arthritis. The subtypes of IgG in these cryoprecipitates were predominantly the complement-fixing IgG1 and IgG3, HBsAg and anti-HBs were concentrated several-fold in the cryoprecipitates when compared to the serum concentration. Sequential studies in two patients demonstrated that the initial appearance of anti-HBs in the cryoprotein complex was associated with the detection in the complex of IgM suggesting a primary immune response to HBsAg. The C3 activator fragment (C3A) of the properdin complex was found in fresh serum obtained from three hepatitis patients with arthritis and not in uncomplicated hepatitis. The cryoprecipitable immune complexes from patients with arthritis converted C3PA in fresh normal sera to C3A in vitro whereas cryoprotein isolated from patients with uncomplicated hepatitis had no such effect. Thus, the transient appearance of circulating complement-fixing immune complexes in patients with the arthritis of acute hepatitis is associated with activation of both classical and alternate complement pathways and suggests that they play an important role in the pathogenesis of these serum sickness-like extrahepatic symptoms.

Acute Disease↗
PubMed1975

Serial studies of hepatitis-associated antigen and antibody in patients receiving antitumor chemotherapy for myeloproliferative and lymphoproliferative disorders.

The effects of antitumor chemotherapeutic agents on hepatitis B antigen (HBAg) and antibody (HBAb) were studied serially in 25 patients with myeloproliferative and in 60 patients with lymphoproliferative disorders. HBAg was detected at some time in 17 patients, and HBAb in 40 patients. Seventeen patients who had HBAb detected immediately pretreatment had a decrease in HBAb titer which paralleled the fall in white blood cell count. In 5 of these patients, HBAg appeared when HBAb titers fell. In 3 of the 5 patients, a reappearance of HBAb was observed with disappearance of HBAg from the serum, and in the 2 other patients HBAg persisted once it appeared. In all 3 patients who had HBAg at the time of initiation of chemotherapy, bone marrow suppression was associated with a marked increase in HBAg titer. The increase in HBAg titer was associated with hepatocellular damage, as manifested by an elevation in serum transaminase enzymes. These observations suggest that antitumor chemotherapeutic agents reduce HBAb titers. In some patients, HBAg appears after a decrease in HBAb titers. In patients with preexisting HBAg, such therapy leads to large increases in HBAg titer. Whether this appearance or increase of HBAg is related to an inhibition of antibody formation, allowing expression of preexisting antigen, or to an inhibition of cellular immunity, allowing viral proliferation, is uncertain.

Adolescent↗
PubMed1975

Arthritis associated with chronic active hepatitis: complement activation and characterization of circulating immune complexes.

Circulating immune complexes were identified in cryoproteins isolated from serial serum samples from 6 to 10 patients with chronic active hepatitis (CAH) with frank arthritis and arthralgias. These immune complexes were not detectable in patients with uncomplicated CAH. Only cryoprecipitates from CAH patients with frank arthritis contained IgG, IgM, IgA, and complement components C3, C4, and C5. Hepatitis B surface antigen was concentrated several-fold in the cryoprotein immune complexes as compared with the serum concentration. The C3 activator fragment of the properdin complex was found in fresh serum in all patients with arthritis but was undetectable in patients with arthralagias and uncomplicated CAH. Thus, the presence of circulating complement-fixing immune complexes in patients with alternate complement pathways, and suggests that they play an important role in the pathogenesis of the arthritis.

Adult↗