Abnormality in immunoregulatory cells in human malignancies.
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Breast Neoplasms↗
Biomedical subjects
S Gupta
Publications and source records attributed to S Gupta.
Natural killer cell and islet killer cell activities in type 1 (insulin-dependent) diabetes.
Peripheral blood mononuclear cells from 20 Type 1 (insulin-dependent) diabetic patients were examined for natural killer cell activity using the K562 cell line as 51Cr labeled targets. Mean natural killer cell cytotoxicity mediated by enriched non-T cells from patients (37 +/- 4.0%) was lower (p less than 0.03) than in controls (56 +/- 3.7%). Specificity was evaluated by examining other patient subgroups. Mean non-T cell mediated natural killer cell activity in Type 2 (non-insulin-dependent) diabetic patients and Type 1 patients with long term disease was 65 +/- 5.4% and 62 +/- 4.8% respectively (p less than 0.003 vs new onset Type 1 patients). Longitudinal studies of new onset Type 1 patients during the remission (honeymoon) phase revealed persistently impaired natural killer cell activity in 3 of 4 patients. In 30 new onset and 11 remission Type 1 diabetic patients, mean non-T cell-mediated cytotoxicity was also measured using dispersed 51Cr labeled islet target cells. Mean islet cytotoxicity mediated by cells from new onset patients was 34 +/- 2.4%, whereas in non-diabetic control subjects mean cytotoxicity was 25 +/- 1.8% (p less than 0.005). During remission, islet cytotoxicity remained at similar or elevated levels in most patients. In patients evaluated simultaneously for K562 and islet cell cytotoxicity, natural killer cell activity was decreased, whereas islet killing was increased. These results suggest a dichotomy in natural killer cell and islet killer cell activities in new onset Type 1 diabetes that could have an important role in the pathogenesis of Type diabetes.
Adolescent↗
Abnormality of Leu 2+7+ cells in acquired immune deficiency syndrome (AIDS), AIDS-related complex, and asymptomatic homosexuals.
Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC), asymptomatic homosexuals, and healthy heterosexuals were analyzed for the proportions and numbers of Leu 7+ cells and double-labeled Leu 2+7+ cells and for the natural killer functions. A significant increase in the proportions and numbers of Leu 7+ cells was observed in patients with AIDS and ARC and in asymptomatic homosexuals compared to healthy heterosexual men. The proportions of Leu 2+7+ cells were significantly increased in AIDS, ARC, and asymptomatic homosexuals, whereas the numbers were increased in asymptomatic homosexuals and ARC but not in AIDS compared to heterosexual controls. A significant increase in the number of Leu 2+7+ cells was observed in AIDS with Kaposi's sarcoma but not in AIDS with opportunistic infections. The natural killer function was significantly depressed in patients with AIDS and ARC and in asymptomatic homosexuals. These data suggest that the quantitative abnormalities of Leu 2+7+ cells appear early during the evolution of immunologic changes in HTLV III/LAV infection.
AIDS-Related Complex↗
Treatment of the acquired immune deficiency syndrome.
The acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) are sequelae of immune system injury initiated by a novel human retrovirus [human T-lymphotrophic virus strain III/lymphadenopathy-associated virus (HTLV III/LAV)]. The resulting spectrum of immune deficiency sets the stage for opportunistic infection and malignancy. In this review, we consider progress made in the treatment and prevention of AIDS and HTLV III/LAV infection. Immunomodulator and antiviral approaches are discussed.
Acquired Immunodeficiency Syndrome↗
Metabolic basis for asthma and rhinitis: an integrated approach.
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Animals↗
Whipple's disease with unusual clinical, bacteriologic, and immunologic findings.
A middle-aged man was found to have Whipple's disease after episodes of nephritis and arthralgia. While on antibiotic therapy, and in the absence of worsening of the histologic appearances of the jejunum, aortic valve endocarditis developed, presumably due to Whipple's disease. Observations during the course of his illness included the isolation of Corynebacterium bovis from an inguinal lymph node, and detection of circulating antibodies against material within the characteristic abnormal macrophages present in the gastrointestinal mucosa. This antigen-antibody reaction was specifically blocked by the monosaccharide rhamnose, a component of the polysaccharide surface coat of many bacteria, including C. bovis.
Antibody Formation↗
Serum lipids of Indian physicians living in the U.S. compared to U.S.-born physicians.
Reports of increased susceptibility of persons from the Indian subcontinent to coronary heart disease led us to examine serum lipids and apolipoproteins in a group of physicians born in India now living in the U.S. A matched sample of U.S.-born physicians working at the same institution was recruited as controls. Fasting triglyceride (TG) levels were twice as high among the Indians (174 vs 86 mg/dl, P = 0.002), total cholesterol modestly increased (193 vs 177 mg/dl, P less than or equal to 0.01) and high density lipoprotein-cholesterol (HDL-C) fraction depressed 36 vs 40 mg/dl, P = 0.006). Both TG and HDL-C were strongly determined by relative obesity in the Americans, but not among the immigrants. Calculated values of low density lipoprotein-cholesterol (LDL-C) were similar in the two groups. Apolipoprotein A-I was significantly lower in a subsample of the Indians, while Apo B was higher. Minor differences between the groups in body mass index, food frequency intake, smoking patterns, alcohol intake and exercise did not significantly influence the results. Hereditary differences in lipid metabolism may have a role in these findings, however, the delayed effects of adaptation to U.S. lifestyle cannot be ruled out.
Adult↗
Study of activated T cells in man. II. Interleukin 2 receptor and transferrin receptor expression on T cells and production of interleukin 2 in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex.
Because the expression of interleukin 2 (IL-2) receptor and transferrin receptor is essential for the proliferation of T cells to mitogens and antigens, we examined the expression of monoclonal antibody defined IL-2 receptor (Tac antigen) and transferrin receptor on unstimulated as well as on phytohemagglutinin (PHA)-activated highly enriched T cells from patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). A trend of increased proportion of unstimulated T cells with Tac antigen and transferrin receptor was observed in patients with AIDS and ARC when compared to healthy heterosexual controls, but the differences were not significantly (P greater than 0.1). The proportions of Tac+ PHA-activated T cells were, however, significantly decreased in AIDS (P less than 0.001). ARC (P less than 0.001), and asymptomatic homosexuals (P less than 0.01) when compared to healthy heterosexuals. The proportions of transferrin receptor positive PHA-activated T cells were not significantly different among various groups. A significantly (P less than 0.01) decreased production of IL-2 was observed in AIDS. This study suggests that the poor proliferative responses of T cells may be due to several defects in lymphocyte-cytokine cascade and the deficiency of Tac antigen expression and of the production of IL-2 could be a few of several abnormalities contributing to poor T-cell functions in AIDS.
Acquired Immunodeficiency Syndrome↗
Autologous mixed lymphocyte reaction (AMLR) in man. XVI. The AMLR and monoclonal antibody-defined T cell subsets and HNK 1+ natural killer cells in normal human pregnancy.
Peripheral blood mononuclear cells from 27 pregnant women and 10 age-matched non-pregnant women were examined for monoclonal antibody-defined T cells, immunoregulatory T-cell subsets, natural killer cells, activated T cells and surface Ig+B lymphocytes using a fluorescence-activated cell sorter (FACS analyzer). The autologous mixed lymphocyte reaction (AMLR) and in vitro influence of interleukin 1 (IL-1) and interleukin 2 (IL-2) on the AMLR were also studied. No significant difference was observed in the proportions of Leu 3+ (helper/inducer phenotype) and Leu 2+ (suppressor/cytotoxic) T cells during all three trimesters of pregnancy and in post-partum period when compared to non-pregnant healthy control women. T cells expressing DR antigen (evidence of T-cell activation) were significantly increased during second trimester (P less than 0.02) and in post-partum period (P less than 0.05). However, Tac+ T cells (IL-2 receptor positive T cells, another but distinct marker for T cell activation) were normal throughout pregnancy and in the post-partum period. Leu 7+ (HNK 1+) lymphoid cells (containing a population of natural killer cells) were normal during all 3 trimesters of pregnancy but were increased during post-partum period. Surface Ig+B cells were comparable to control group throughout pregnancy and during post-partum period. The AMLR was significantly deficient (P less than 0.01) during first and third trimester of pregnancy. In vitro addition of purified IL-2 restored the AMLR to the baseline levels of the controls but the AMLR was still lower than the levels in controls with IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Effect of intratracheal injection of zinc oxide dust in guinea pigs.
Intratracheal injection of zinc oxide dust, a component of many cosmetic preparations caused elevation of alkaline phosphatase and lactate dehydrogenase in serum and lung of guinea pigs. Clearance of zinc oxide dust from lungs through zinc-carrying proteins was evident.
Alkaline Phosphatase↗
Anti-ulcerogenic effect of banana powder (Musa sapientum var. paradisiaca) and its effect on mucosal resistance.
Orally administered banana pulp powder (Musa sapientum var. paradisiaca) was shown to have significant anti-ulcerogenic activity in rats subjected to aspirin, indomethacin, phenylbutazone, prednisolone and cysteamine and in guinea-pigs subjected to histamine. Banana powder not only increased mucosal thickness but also significantly increased [3H]thymidine incorporation into mucosal DNA. Relative to untreated control sections, histological studies showed that banana treatment increased staining by alcian blue in the apical cells with staining noted in the deeper layers of the mucosal glands. Banana-treated and control sections were also stained for DNA by the Feulgen reaction. The banana-treated sections showed a greater aggregation and intensity of pink spots when compared to controls. The present study suggests that banana powder treatment not only strengthens mucosal resistance against ulcerogens but also promotes healing by inducing cellular proliferation.
Animals↗
Studies in potential filaricides. 18. Synthesis of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds as potential anthelmintics.
A series of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds have been synthesized of which 2,2'-bis(carbomethoxyamino)-5,5'-dibenzimidazolyl ketone exhibited a broad spectrum of anthelmintic activity in experimental animals. At doses of 10-50 mg/kg given intraperitoneally, 5 killed 100% of the adult worms of Litomosoides carinii, Dipetalonema viteae, and Brugia malayi. By the oral route the macrofilaricidal efficacy of 5 was 97-100% at 100-200 mg/kg X 5 days. The treated animals showed gradual disappearance of microfilariae and before autopsy they became amicrofilariaemic. Some of the compounds also showed 100% efficacy against the human hookworms and tapeworm, Ancylostoma ceylanicum in hamsters, and Hymenolepis nana in rats at a single oral dose of 50-250 mg/kg. Compound 5 was also effective against Syphacia obvelata in mice at a single oral dose of 100 mg/kg and was found to be well tolerated by mice up to an oral dose of 2500 mg/kg.
Animals↗
Cyclosporin A corrects daunorubicin resistance in Ehrlich ascites carcinoma.
We have previously developed a daunorubicin resistant subline of Ehrlich ascites carcinoma (EA/DR) for studies on the reversal of daunorubicin resistance. The mean survival of untreated BALB/c mice bearing drug sensitive parental tumour (EA/DS) is 18.4 +/- 0.6 days, mice bearing EA/DS treated with five daily doses of 0.3 mg kg-1 daunorubicin greater than 60 days, and mice bearing EA/DR treated with the same daunorubicin regimen, 21.1 +/- 1.4 days. We now report complete reversal of daunorubicin resistance in EA/DR by cyclosporin A (CsA). The in vitro daunorubicin IC50, defined as that concentration of daunorubicin required to inhibit 50% of DNA synthesis, in EA/DR was 6.7 +/- 1.15 micrograms ml-1 compared to 2.8 +/- 0.72 micrograms ml-1 in EA/DS. This value was reduced to 2.8 +/- 0.52 and 2.1 +/- 0.10 micrograms ml-1 daunorubicin by 3.3 and 13.2 micrograms ml-1 CsA respectively, P less than 0.05. The MST of groups of host mice bearing EA/DR either untreated, treated with five daily doses of 0.3 mg kg-1 daunorubicin, treated with 80 mg kg-1 CsA in five divided daily doses or treated with combined daunorubicin-CsA were 19.0 +/- 1.0, 21.1 +/- 1.4, 24.0 +/- 2.6 and greater than 60 days respectively. The mean survival of groups of host mice bearing EA/DR treated with 5 mg kg-1 or 10 mg kg-1 CsA simultaneously with daunorubicin for five days was also greater than 60 days. These differences are highly significant.
Animals↗
A randomized double-blind trial of cholecystokinin during ERCP.
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Catheterization↗
Immune thrombocytopenic purpura, neutropenia and sclerosing cholangitis associated with ulcerative colitis in an adult.
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Adult↗
Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 inhibit mitogen-induced human mononuclear cell proliferation.
Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 were found to inhibit human peripheral blood mononuclear cell (MNC) proliferation (measured by [3H]thymidine uptake) that was induced by concanavalin A or monoclonal antibody OKT3. These antimicrobial agents exert their maximum suppressive effect when added within the first 24 h after the onset of culture with concanavalin A. No increase in the concentration of mitogen or the duration of incubation of MNC cultures reversed this inhibitory effect, but the removal of the drug from cultures reversed the suppression of DNA synthesis. A-56619 appeared not to interfere with the triggering of MNC activation by mitogen because it did not inhibit mitogen-induced increase in protein synthesis (measured by [3H]leucine incorporation), interleukin-2 receptor expression (measured by the binding of fluorescein-conjugated monoclonal antibody against interleukin-2 receptor), and cell volume. These findings are considered in terms of possible interference of aryl-fluoroquinolones with mammalian topoisomerase and DNA polymerases.
Anti-Infective Agents↗
Effects of nonleukemogenic and wild-type Moloney murine leukemia virus on lymphoid cells in vivo: identification of a preleukemic shift in thymocyte subpopulations.
Infection of mice with Moloney murine leukemia virus (M-MuLV) as well as with a nonpathogenic variant, Mo+PyF101 M-MuLV, was studied. Mo+PyF101 M-MuLV differs from wild-type M-MuLV by the addition of enhancer sequences from polyomavirus in the long terminal repeat. Previous experiments indicated that Mo+PyF101 establishes infection in animals, even though it does not induce disease. In vivo infection studies with particular attention to the thymus were performed, since the thymus is the target organ for M-MuLV leukemogenesis. Mice inoculated at birth with wild-type M-MuLV developed maximal levels of thymic infection by 2 to 3 weeks. Animals inoculated with Mo+PyF101 M-MuLV showed considerably less thymic infection at early times (2 to 4 weeks); nevertheless, by 5 to 6 weeks infection equivalent to wild-type M-MuLV-inoculated animals developed. Therefore the nonpathogenicity of Mo+PyF101 M-MuLV did not simply reflect a lack of thymotropism. Furthermore, thymic infection by itself may not be sufficient to induce leukemia. The relative deficit of Mo+PyF101 M-MuLV thymic infection at early versus late times did not reflect a change in the nature of the cells in the thymus, since in vitro infection of primary thymocytes from 2- and 6-week-old animals was equally efficient. One possible explanation is that infected thymocytes normally arise from progenitor cells which were infected in the bone marrow or spleen, and the cells restricted for Mo+PyF101 M-MuLV are located in those organs. Comparison of wild-type and Mo+PyF101 M-MuLV also allowed identification of important preleukemic changes in the thymus of wild-type M-MuLV-inoculated mice. Flow cytometry with monoclonal antibodies specific for thymocyte subpopulations was used. Staining of cells for Thy-1 or Thy-1.2 antigens indicated a shift toward low or negative cells. A concomitant increase in cells positive for antigen Pgp-1 was also observed. This is consistent with an increase in the relative frequency of immature blastlike cells. Importantly, thymuses from mice inoculated with Mo+PyF101 M-MuLV did not show these shifts in thymocyte subpopulations.
Animals↗
Effect of a slow-release 5'-aminosalicylic acid preparation on disease activity in Crohn's disease.
A short-term double-blind controlled trial has been performed comparing a slow-release 5'-aminosalicylic acid (5-ASA) tablet (Pentasa) with placebo in the outpatient treatment of mild and moderate active Crohn's colitis. The disease activity was measured objectively by quantitation of the faecal excretion of 111In-labelled autologous granulocytes, which directly reflects gut inflammation. Twelve patients were randomized to receive either Pentasa or placebo. After 10 days of treatment faecal granulocyte excretion fell in all patients receiving 5-ASA, while no consistent change was found in the placebo group. These results suggest that this slow-release preparation of 5-ASA should be tested in larger controlled therapeutic trials over a longer period of time.
Adult↗