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Biomedical subjects

R H Tomar

Publications and source records attributed to R H Tomar.

At least 37 records · Page 2Linked to original sources

Soluble interleukin 2 receptors are elevated in patients with AIDS or at risk of developing AIDS.

Utilizing an enzyme-linked immunosorbent assay, we detected elevated serum levels of soluble interleukin 2 receptors (SIL-2R) in 73% of patients with acquired immunodeficiency syndrome (AIDS), 80% of AIDS-related complex patients, 78% of anti-HIV-positive lymphadenopathy syndrome patients, 85% of HIV-antibody-positive hemophiliacs, and 80% of anti-HIV-positive asymptomatic homosexual males, iv drug abusers, and heterosexual contacts. Of the subjects with no demonstrable antibody to HIV, 29% of hemophiliacs, 12% of adult homosexual males and iv drug abusers, and none of the patients with lymphadenopathy had elevated SIL-2R. Overall, only 5 of 40 antibody-negative "high-risk" individuals had SIL-2R values greater than the reference interval whereas 108 of 138 antibody-positive individuals had elevated values (chi 2 = 57.85, P less than 0.001).

AIDS-Related Complex↗

Serum immunoglobulins and lymphocyte subsets in chronic lymphocytic leukemia.

The concentrations of serum immunoglobulins were correlated to the stage of disease and the proportions of peripheral blood lymphocyte subsets in 25 untreated patients with B-cell chronic lymphocytic leukemia (CLL). Diminished levels of at least one serum immunoglobulin were present in 77% of all patients with CLL and 73% of patients with Stage 0 disease. The mean concentration of IgG, IgM, and IgA decreased with advancing stage of CLL. The percentages of total T, T-helper (TH), and T-suppressor (TS) cells in the peripheral blood were less in patients with CLL than in healthy persons, but the absolute concentrations of total T, TH, and TS cells were greater in patients with CLL than controls (P less than 0.02). The absolute number of B-cells (P less than 0.01) and null cells (P less than 0.001) was also increased in patients with CLL, particularly those patients in advanced stages of CLL. These findings suggest that the hypogammaglobulinemia associated with CLL first occurs during the earliest stage of disease and may be related to the alterations in the proportion of peripheral blood lymphocytes.

Adult↗

The mechanism of enhancement of natural killer cell activity by soluble streptococcal products.

Products prepared from broth extracts of beta-hemolytic Group A streptococci activate human natural killer (NK) cells. The active moiety is likely a protein since the enhancing capability is destroyed by the proteolytic enzyme pronase, although not by trypsin. The enhancement in NK cytotoxicity is due at least in part to lymphokines, since normal peripheral blood mononuclear cells and T cells, upon incubation with streptococcal products (SP), release supernatant factors which augment NK activity. These cell culture supernatants contain interferons (IFN) as well as low levels of interleukin-2 (IL-2). Treatment of supernatants with anti-IFN antibodies has variable effects, depending on the donor cells used to produce the factors. In most cases, anti-IFN-gamma totally abrogates enhancement. Treatment of supernatants with antibodies to IFN-alpha modestly decreases enhancement of most donor cells; however, IFN-alpha appears not to be a major factor in SP-activated lymphokines. Pretreating effector cells with a monoclonal antibody directed against the IL-2 receptor (anti-Tac) usually reduces the supernatant effect. The combination of anti-Tac and anti-IFN-gamma totally nullifies enhancement. Thus T lymphocytes stimulated with streptococcal products augment NK activity at least in part by producing IFN-gamma and a factor whose activity is reduced by the interaction of the IL-2 receptor with anti-Tac.

Antibodies↗

Decreased natural cytotoxicity in mice with high incidence of mammary adenocarcinoma.

In an attempt to gather evidence relevant to the question of whether natural killer (NK) cells play a role in resisting the development of primary tumors, we compared natural cell-mediated cytotoxicity in two substrains of C3H mice. Animals of the C3H/OuJ substrain are at high risk for the formation of mammary adenocarcinomas, while C3Heb/FeJ mice have a low incidence of such tumors. Natural cytotoxicity of splenic mononuclear cells was lower in the high-risk substrain, suggesting that a lesion in NK cell activity may be involved in murine mammary tumorigenesis. This difference was observed in animals between 5 and 37 weeks of age. There was no significant difference in the number of splenic large granular lymphocytes between the substrains. A significant difference in the ability of splenic lymphocytes from the two substrains to bind to the target cells was noted. Since the binding capacity of lymphocytes was greater in mice with reduced NK cell activity, the lesion in cytotoxicity may exist at a postbinding step in the lytic sequence. It is felt that the C3H mouse may provide a useful model for studying the role of NK cells in controlling primary tumors.

Adenocarcinoma↗

Impaired interleukin regulation of the phytohemagglutinin response in Hodgkin's disease.

Patients with active Hodgkin's disease (HD) often demonstrate an impaired T-cell proliferative response to phytohemagglutinin (PHA). The present study examined if interleukin regulation of the PHA response was defective in HD. The Hodgkin's PHA response was impaired at all concentrations of PHA utilized. Indomethacin increased the proliferative response but did not bring it to control levels. Stimulation of the cells with both PHA and irradiated Ia+ B cells normalized proliferation despite identical PGE2 concentrations as in the PHA alone cultures. Hodgkin's monocytes produced normal amounts of interleukin 1 (IL-1). Interleukin 2 (IL-2) production by Hodgkin's T cells was decreased in the PHA stimulated cultures, but was normal in the PHA and Ia+ cell stimulated cultures. In response to PHA stimulation alone, Hodgkin's T cells expressed less IL-2 receptor than control cells. The data suggest the diminished PHA response in HD is due to impaired IL-2 production resulting in diminished IL-2 receptor expression. However, when an Ia+ cell source is added to PHA as an additional stimulator, both TCGF production and proliferation are normalized. Monocytes serve to modulate the magnitude of the PHA response through production of both interleukin 1 and PGE2. However, in the presence of sufficient IL-2 production the influence of monocytes is minimized.

Adult↗

Cellular targets of antilymphocyte antibodies in AIDS and LAS.

Many patients with acquired immune deficiency syndrome (AIDS) and lymphadenopathy syndrome (LAS) have serum antilymphocyte antibodies. The targets of these antibodies are neither sex nor HLA directed. There is disagreement about the cell subset at risk. We examined the cellular specificity of antilymphocyte antibodies from AIDS and LAS patients by microcytotoxicity on positively selected lymphocytes, by using double-labeling immunofluorescence, and by using well-characterized continuous cell lines as targets. We find that most AIDS/LAS patients have antibodies to T and B cells, that immunofluorescence is somewhat more sensitive than microcytotoxicity, and that the antibodies are directed to both T4+ and T4- lymphoid cells.

Acquired Immunodeficiency Syndrome↗

Antibodies to human T-cell lymphotropic virus-I membrane antigens and inverted T4/T8 ratios in hemophiliacs.

Antibodies to the membrane antigens of human T-cell lymphotropic virus-I (anti-HTLV-MA) have been detected in patients with the acquired immune deficiency syndrome (AIDS) and in patients with hemophilia. The authors examined sera from 71 AIDS patients and 46 hemophiliac children for the presence of anti-HTLV-MA using an indirect membrane immunofluorescence assay with flow cytometry analysis. Thirty-seven of the 71 (52%) AIDS patients and 7 of the 46 (15%) hemophiliac patients had high titered anti-HTLV-MA, using a T-lymphoid cell line infected with the leukemia virus. None of the 78 control subjects had high titered antibody. All seven hemophiliac patients with elevated anti-HTLV-MA used Factor VIII concentrates, and all had inverted T-lymphocyte helper-suppressor (T4 [Leu-3]/T8 [Leu 2]) ratios. No correlations were found between inverted T4/T8 ratios and antibody to cytomegalovirus, Toxoplasma gondii, or hepatitis B. This work supports contentions that HTLV-like organisms cause AIDS and that these organisms are transmitted by blood products such as Factor VIII concentrate.

Acquired Immunodeficiency Syndrome↗

T cell growth factor required for optimal induction of T cell growth factor receptor expression in phytohemagglutinin-stimulated T cells.

Proliferation of normal human T cells in vitro requires activation of resting T cells by lectin or antigen. This stimulation initiates a series of events which includes elaboration of T cell growth factor (TCGF), expression of TCGF receptors, and, ultimately, cellular proliferation. We sought to determine if TCGF was required for expression of the TCGF receptor in phytohemagglutinin (PHA)-stimulated normal human T cells. Utilizing dexamethasone (DEX), a known inhibitor of TCGF production, reductions in T cell proliferation, TCGF production, and TCGF receptor expression, as measured by TCGF adsorption and Tac acquisition, were demonstrated after PHA stimulation. When exogenous partially purified TCGF was added to DEX-containing cultures, the DEX inhibition of proliferation and TCGF receptor expression was completely reversed. These experiments were reproduced utilizing both highly purified TCGF from the Jurkat cell line and purified TCGF synthesized by bacteria from cloned TCGF DNA. Short-term experiments showed TCGF to be capable of restoring Tac antigen expression after DEX inhibition in the absence of cellular proliferation. These results indicate that TCGF is required for optimal expression of Tac antigen-associated TCGF receptors in PHA-activated T cells.

Antigens, Surface↗

Paraproteinemia in patients with acquired immunodeficiency syndrome (AIDS) or lymphadenopathy syndrome (LAS).

Eight of 15 patients with acquired immunodeficiency syndrome (AIDS) and six of nine patients with lymphadenopathy syndrome (LAS) had paraproteins in their sera. Twelve of these 14 were IgG kappa; the other two had no demonstrable light chains. The relationship of the paraprotein to the pathogenesis of AIDS is not clear, but we discuss its relation to derangements of B-cell immune regulation and function and to B-cell tumors in AIDS patients.

Acquired Immunodeficiency Syndrome↗

Lymphocytotoxic antibodies in the acquired immune deficiency syndrome (AIDS).

The acquired immune deficiency syndrome (AIDS) manifested by opportunistic infections or Kaposi's sarcoma is a newly recognized and often fatal disease. Three patients seen in Syracuse, New York, were noted to have lymphopenia and persistent serum lymphocytotoxic antibodies (LCTAs). In a double blinded study, 25 serum samples were coded and sent to us by the Centers for Disease Control Task Force on Kaposi's Sarcoma and Opportunistic Infections. Samples from 5 patients with Pneumocystis carinii pneumonia, 5 patients with Kaposi's sarcoma, 5 presumably healthy homosexual males, 5 presumably healthy heterosexual males, and 5 presumably healthy heterosexual females were included. Of the ten AIDS patients, nine had "positive" or "suspicious" results on testing for lymphocytotoxic antibodies. The five heterosexual male and five heterosexual female controls had "negative" results. Of the five homosexual male "controls," three had "positive" or "suspicious" LCTA results. Two of these three "controls" were available for follow-up. Both showed deficiencies in studies of their cell-mediated immunity. Lymphocytotoxic antibodies may participate in the ongoing immunodeficiency seen in AIDS.

Acquired Immunodeficiency Syndrome↗

Inhibition of in vitro lymphocyte proliferation by serum from acquired immune deficiency syndrome patients depends on the ratio of cells to serum in culture.

The effect of serum from patients with acquired immune deficiency syndrome (AIDS) on cultures of normal human peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA) has been studied. It has been found that AIDS sera are inhibitory when compared with control sera from healthy individuals. The inhibitory activity in the AIDS patients' sera is dilutable with normal serum, is dependent on the number of cells present in culture and the amount of serum added, and cannot be attributed to a deficiency of nutrients in these sera. Inhibition of proliferation occurs even when AIDS serum is added to cultures of normal cells several hours after stimulation with PHA. In one patient who was being treated with plasmapheresis, decreases in serum inhibitory activity were found after pheresis procedures and were coincident with increases in the number of circulating T4-positive lymphocytes.

Acquired Immunodeficiency Syndrome↗

Plasmapheresis increases T4 lymphocytes in a patient with AIDS.

Previously the authors demonstrated that most patients with AIDS have serum antilymphocyte antibodies. Therefore, in an attempt to decrease these antibodies and at least transiently increase blood lymphocytes, they treated one AIDS patient with three courses of plasmapheresis. During or after each course, his T4 lymphocytes rose significantly but subsequently fell to baseline values within two weeks after therapy. The increase in T4 lymphocytes was associated with removal of patient plasma rather than infusion of heterologous plasma. These results suggest the need for more investigation into plasmapheresis as adjunct therapy for AIDS.

Acquired Immunodeficiency Syndrome↗

Autoimmune phenomena in infertile patients with endometriosis.

To assess the presence of autoimmune factors in patients with endometriosis, endometrial homogenates, peritoneal fluid, and serum were evaluated in 23 patients with endometriosis and 22 control subjects. The methods used were Ouchterlony immunodiffusion, immunoelectrophoresis, polyacrylamide gel electrophoresis, and radial immunodiffusion. The study demonstrated precipitation lines between endometrial homogenates and serum from some endometriosis patients but not from the control subjects. Immunoelectrophoresis demonstrated precipitation lines at beta-globulin position when endometrial homogenates were used against serum of patients with endometriosis and with goat antihuman serum. It is suggested that an antigen, possibly a glycoprotein, is present in the endometrial homogenates. Radial immunodiffusion studies for immunoglobulins (Ig) G, A, and M and complement components C3c and C4 showed significantly higher concentrations of C3c and C4 in serum and peritoneal fluid of patients with endometriosis than the control subjects (P less than .05). There was no significant difference in concentration of IgG, A, M, factor B, and properdin.

Adolescent↗

Bacteremia following prosthetic valve replacement.

The outcome of patients developing early bacteremia was investigated in 890 patients following cardiac valve replacement over a ten-year period. Thirty-two patients developed bacteremia during the hospital recovery period from valve replacement (3.6%). Sixty per cent of the organisms involved were gram-negative. Twenty-one of 23 patients had white blood counts greater than 14,000 at the time of positive blood culture. Nine patients died, seven of septic complications. Only two patients developed endocarditis. No patient with bacteremia diagnosed within ten days of surgery developed endocarditis, however two patients developed gram-negative sepsis in this period. The diagnosis and treatment of bacteremia requires continual vigilance if significant mortality and morbidity are to be averted.

Aged↗

Predicting acute vs chronic childhood idiopathic thrombocytopenic purpura.

We studied 12 children with idiopathic thrombocytopenic purpura (ITP) to determine if selected immune measurements could prospectively distinguish chronic ITP from acute ITP. Immunologic assessment included immunoglobulin levels, T- and B-cell enumeration, in vitro lymphocyte stimulation by phytohemagglutinin, and a screen for autoantibodies. The most consistent difference observed was that unstimulated lymphocytes in chronic ITP had an increased basal rate of thymidine incorporation. The same assays were performed on eight other children in whom the diagnosis of chronic ITP already had been established. A similar abnormality was found in this group. Study of lymphocyte proliferation in patients with ITP appears useful in predicting the course of the disease.

Acute Disease↗