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Biomedical subjects

M L Tiku

Publications and source records attributed to M L Tiku.

At least 37 records · Page 2Linked to original sources

Immunobiological function of normal rabbit synovial cells.

The ability of enzyme-dissociated primary cultures of synovial cells (Sy) to present antigen was investigated. Adult rabbits were immunized in foot pads with bovine serum albumin (BSA) in complete Freund's adjuvant (CFA) or with CFA alone. Four to six weeks later draining popliteal lymph node cells (LNC) and synovial cells were obtained. Synovial cells were cultured overnight with or without antigen. About 20% of these synovial cells had Fc receptors and 15% C3 receptors. As a positive control splenic adherent cells (SAC) were similarly treated. Next day, autologous lymph node cells were added to the extensively washed and irradiated synovial cells or splenic adherent cells. Lymphocyte proliferation was measured by [3H]thymidine uptake. Synovial cells as well as splenic adherent cells induced mixed lymphocyte reaction (MLR) and autologous mixed lymphocyte reaction (AMLR) and effectively presented antigen for specific immune response to the priming antigen. Thus, the synovium contains macrophage-like cells that can effectively interact with lymphocytes and participate in the immune phenomena in the joints of patients with rheumatoid arthritis.

Animals↗

Enhancement of endothelial plasminogen activator synthesis by lymphokines.

Long-term cultures of pig aortic endothelial (E) cells secrete plasminogen activator (PA). When these cells were cultured with murine lymphokine(s) produced in response to antigen, mitogen, or allogeneic stimuli, there was consistently increased PA secretion by E cells. The evidence suggests that initiator of plasminogen activator (IPA) is produced by a nylon-wool--nonadherent cell, probably a T cell. The kinetics of this activation of PA suggest that the effect of IPA on E cells is considerably delayed compared with that on phagocytic cells. The significance of these findings is discussed in terms of their possible relationship to several immunopathological states.

Animals↗

Macrophage-related fibrinolysis in experimental disseminated histoplasmosis.

A model of disseminated histoplasmosis in CBA/J mice was developed. Cultures of Histoplasma capsulatum from the spleens of infected mice suggested almost complete clearance of fungi by week 3. The adherent spleen cells from infected mice showed a 2- to 20-fold increase in fibrinolysis. The increase in activity was maximal around 1 to 2 weeks and disappeared after week 3 of infection, and this paralleled the progressively decreasing number of culturable fungi from the spleen. In vitro coculture of infected spleen cells or nylon wool-purified immune T cells and proteose peptone-induced macrophages resulted in increased fibrinolysis. Peritoneal exudate cells from infected mice also showed increased fibrinolysis. The addition of soluble antigen to an in vitro culture system resulted not only in an increase in fibrinolytic activity of peritoneal exudate cells derived from infected mice but also of proteose peptone-induced macrophages. These observations suggest that spleen and peritoneal macrophages from H. capsulatum-infected mice exhibit increased fibrinolysis which in turn is indicative of macrophage activation. The mechanism of activation occurs as a result of immunologically specific T cell-macrophage interaction and by the action of histoplasma products on the macrophages. The significance of these findings and the role of the plasminogen activator assay in studies of disseminated fungal infection are discussed.

Animals↗

Class II histocompatibility antigen-mediated immunologic function of normal articular chondrocytes.

Using monoclonal antibodies, we examined the display of rabbit Ia by articular chondrocytes. We found that 29 to 46% of chondrocytes displayed Ia antigen compared with 46 to 60% of spleen cells. Ia antigen expression was not likely to be the result of enzyme treatment. To investigate antigen presenting activity of enzyme dissociated normal articular chondrocytes, adult rabbits were immunized in the front foot pads with ovalbumin (OVA) in complete Freund's adjuvant. Four to six weeks later, draining popliteal lymph node cells (LNC) were obtained. Articular chondrocytes were obtained by overnight collagenase, DNase, and hyaluronidase digestion of cartilage from both ends of femurs and proximal end of tibias. Antigen-presenting cells from spleen were used as positive controls. LNC and nylon wool-purified T cells were cultured with OVA pulsed and mitomycin C-treated chondrocytes or spleen cells, and lymphocyte proliferation was measured by 3H-TdR uptake. Both chondrocytes and spleen cells showed antigen presenting activity, and stimulation of lymphocyte proliferation was inhibited by murine monoclonal anti-rabbit Ia antibody (2C4), whereas control plasmacytoma cell supernatants had no effect. When T cells were purified first by Sephadex G-10 and later by nylon wool columns, these cells were dependent on antigen-presenting cells for immunogen (OVA)-induced lymphocyte proliferation. Again, chondrocytes under these strict experimental conditions presented antigen to T cells. Chondrocytes also stimulated autologous and allogeneic normal lymphocytes. Thus, normal chondrocytes have Ia antigens on their surface and can function as antigen-presenting cells. These results are significant for the understanding of local cellular interaction in the pathogenesis of rheumatoid arthritis.

Animals↗

Serum immunoconglutinin titers during acute and chronic hepatitis B virus infection.

Sera from 99 chronic hepatitis B surface antigen carriers, 12 individuals with acute type B hepatitis, 26 hepatitis B surface antibody-seropositive subjects, and 50 hepatitis B surface antigen, hepatitis B surface antibody-seronegative subjects were evaluated for the presence of serum imunoconglutinis (IKs). The mean serum IK titers of hepatitis B surface antibody-seropositive and hepatitis B virus-seronegative subjects wre 5.3 and 4.9, respectively. The IK titers of subjects with acute and chronic hepatitis B virus infections were 215.4 and 19.1, respectively. These groups also manifested IK titers greater than or equal to > 16 significantly (P < 0.005) more often than controls did. Among chronic hepatitis B surface antigen carriers, high IK titers were associated with low levels of hepatitis B surface antigen. IK titers of individuals chronically infected with hepatitis B virus and having the rheumatoid factor were similar to those of individuals without the rheumatoid factor. Elevated IK titers represent a physiological autoimmune response and may indicate the presence of immune complexes in acute and chronic hepatitis B virus infection.

Acute Disease↗

Effects of interferon and adenine arabinoside treatment of hepatitis B virus infection on cellular immune responses.

Fifteen patients with chronic hepatitis B were treated with adenine arabinoside (Ara-A) or human leukocyte interferon (HLI). Cellular immune response to hepatitis B virus surface antigen and antigens prepared from herpes simplex virus, varicella zoster virus, and cytomegalovirus was measured by a lymphocyte blast transformation assay and an assay for interferon production. Measurements were made before, during, and after antiviral treatment. Unlike patients convalescing from acute hepatitis B, only 2 of 15 patients with chronic hepatitis B had significant blast transformation to hepatitis B surface antigen. One such response occurred during the pretreatment period of HLI therapy, and the other was in a patient undergoing low-dose (<10(5) U/kg per day) HLI therapy. Mononuclear cell cultures were tested for interferon production in the presence of hepatitis B surface antigen. Cells from only 1 of 15 patients produced detectable levels of interferon. In contrast, all of these patients had normal cellular immune responses to herpesvirus antigens. Transformation responses to herpes antigens decreased three- to fivefold after patients were treated with >10(5) U of HLI per kg per day. Antiviral therapy with <10(5) U of HLI per kg per day or Ara-A did not produce a detectable depression of transformation response. Ara-A produced marked lymphocytopenia and a marked lymphocyte fragility after 5 or more days of therapy. In vitro Ara-A was toxic to lymphocytes at concentrations as low as 0.5 mug/ml. These changes in lymphocyte parameters may affect the outcome of antiviral therapy.

Acute Disease↗

Immunological aspects of cryoprecipitates from the sera of chronic HBsAg carriers.

The sera of chronic hepatitis B surface antigen (HBsAg) carriers and seropositive controls were examined for the presence of immune complexes by cryoprecipitation. Cryoprecipitates (CP) were tested for HBsAg, antibody to HBsAg (anti-HBs), major classes of immunoglobulins, components of the complement system, rheumatoid factor and the ability to activate the alternative pathway of the complement system. For this analysis the methods employed included: radioimmunoassay, reverse passive haemagglutination, immunofluorescence, sucrose density gradient ultracentrifugation, agar-gel diffusion, immunoelectrophoresis, counterimmunoelectrophoresis, latex agglutination, and a haemolytic method for the detection of the activation of the alternative pathway of the complement system. HBsAg was frequently observed in the CP from chronic HBsAg carriers. No anti-HBs activity was detected in the serum of chronic HBsAg carriers. However, the CP from a number of chronic HBsAg carriers contained immunoglobulins and components of the complement system in the absence of rheumatoid factor, anti-HBs activity and were able to activate the alternative pathway of the complement system. On immunoelectrophoresis, a component of the CP reacting with anti-IgG, ANTI-IgA and anti-HBs antisera and demonstrating an altered (faster) electrophoretic mobility was observed. The nature of the CP strongly suggests the presence of circulating immune complexes in asymptomatic chronic HBaAg carriers. These immune complexes may be important in the eventual expression and outcome of clinical disease in apparently healthy carriers of HBsAg.

Adult↗

Cell-mediated immune response to liver tissue antigen and hepatitis B surface antigen after infection with hepatitis B virus in humans.

The in vitro correlates of cell-mediated immunity to liver tissue antigens and hepatitis B surface antigen (HBsAg) were studied in groups of subjects with acute and chronic hepatitis B virus (HBV) infection and in a population of HBV-seronegative controls. The technique of in vitro lymphocyte transformation (LTF) was employed in these studies. No LTF response to liver-specific antigen and HBsAg was observed in the control population. LTF activity in response to HBsAg was present in 11 of the 14 subjects with acute type B viral hepatitis during the early phase of the disease, and eight of these subjects also had LTF reactivity to liver antigen. During the convalescent phase the LTF reactivity to these antigens usually disappeared. More than 70% of patients with chronic carriage of HBsAg who had elevated levels of liver enzymes showed LTF responses to HBsAg, and a significant number of these subjects also exhibited LTF response to liver-specific antigen. On the other hand, chronic HBsAg carriers who persistently showed normal liver enzyme values (asymptomatic carriers) failed to show significant responses to liver antigen or HBsAg. It is suggested that the persistence of cellular reactivity to liver antigens may lead to the establishment of chronic liver disease.

Acute Disease↗

Hepatitis B surface antigen-specific cell-mediated immune responses in human chronic hepatitis B surface antigen carriers.

The presence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), the nature of T-cell function, and specific cell-mediated immunity to HBsAg were determined and evaluated serially in groups of subjects with chronic HBsAg carrier states and in seronegative controls. The techniques of in vitro lymphocyte transformation, spontaneous rosette formation, radioimmunoassay, reverse passive hemagglutination, passive hemagglutination, rheophoresis, and liver function tests were employed for these studies. For the lymphocyte transformation assay, multiple concentrations of phytohemagglutinin and purified HBsAg were used as stimulants. Cell-mediated immunity to HBsAg was detectable in 50% of the chronic HBsAg carriers (responders) at one or more concentrations of HBsAg. The remaining carriers (nonresponders) and controls failed to manifest HBsAg-specific lymphocyte transformation activity. The profile of the responders was characterized by elevated serum glutamic pyruvic transaminase levels, the presence of anti-HBe, high HBsAg titers, and the conspicuous absence of HBeAg in the serum. The nonresponders were characterized by normal serum glutamic pyruvic transaminase levels, the presence of HBeAg and anti-HBe, and lower HBsAg titers. These observations demonstrate the presence of specific cell-mediated immunity to HBsAg in chronic HBsAg carriers who manifest biochemical evidence of liver disease.

Alanine Transaminase↗

Hepatitis B e antigen and antibody activity in hepatitis B virus infection.

Groups of institutionalized subjects, volunteer blood donors with serologic evidence of asymptomatic hepatitis B virus infection, and patients with acute type B viral hepatitis were studied for the presence of hepatitis B e antigen and antibody in a sequential manner over a period of two to three years. HBeAg was detected in 9.5% of institutionalized residents and volunteer blood donors and in 24% of patients with acute type B viral hepatitis. HBeAg positive subjects frequently had persistently elevated pyruvic glutamic transaminase levels in the serum. Anti HBe activity was observed in 26 to 32% of subjects positive for hepatitis B surface antigen. Long-term follow-up indicated that HBsAg positive subjects with anti HBe did not eventually become seronegative for HBsAg.

Adolescent↗

Distribution and characteristics of hepatitis B surface antigen in body fluids of institutionalized children and adults.

Specimens of blood, feces, urine, and nasopharyngeal washings collected at regular intervals from subjects in an institutionalized population were tested for the presence of hepatitis B surface (HBS Ag) and antibody by passive hemagglutination, radioimmunoassay, and immune electron microscopy. HBS Ag, confirmed by radioimmunoassay and immune electron microscopy, was frequently detected in nasal washings, urine, and feces of chronic carriers of HBS Ag and occasionally in subjects with recent seroconversion for HBS Ag. In addition, some subjects who had recently become positive for antibody to HBS Ag in serum had HBS Ag transiently present in urine and occasionally in the feces, without demonstrable antigenemia.

Adult↗

Hepatitis B infection in health care personnel of an institution for mentally handicapped children and adults.

The health care personnel (HCP) of an institution for the mentally handicapped were serially tested for the presence of hepatitis B surface antigen (HBSAg) and antibody over a period of 1.5 years. HBSAg was present in 1.8% and anti-HBS in 20.8% of HCP. The prevalence of seropositive HCP appeared to be related to the age and the prevalence of seropositive residents cared for by the HCP. The occurrence of seropositivity was higher in the HCP who cared for children under 15 years of age, who demonstrated a high prevalence of HBSAg or anti-HBS. Although the prevalence of HBSAg-positive subjects was 4- to 8-fold lower in HCP than in residents, the degree of seroconversion in susceptible seronegative HCP and residents was strikingly similar. These observations suggest that HCP working in a closed institutional setting are at considerable risk of contacting hepatitis B infection.

Adult↗

Evaluation of turkey erythrocyte hemagglutination assay for the detection of hepatitis B antigen.

A recently described hemagglutination test for hepatitis B antigen (HBsAg) using turkey erythrocytes coated with horse antibody to HBsAg purified by affinity column chromatography was evaluated on a comparative basis with 100 HBsAg-positive and -negative serum samples. The turkey erythrocyte hemagglutination test (TEHA) was found to be less sensitive than radioimmunoassay (RIA) but gave far better results than counterimmunoelectrophoresis. Quantitative titration of HBsAg in serial dilutions of the samples appeared to be more reliably performed by TEHA than by RIA. TEHA is a simple and sensitive technique for the detection of HBsAg and may offer several practical advantages over RIA.

Animals↗