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P K Arora

Publications and source records attributed to P K Arora.

At least 37 records · Page 2Linked to original sources
PubMed1990

Strain-dependent association between immune function and paw preference in mice.

The relationship between immune function and the preferred direction of behavioral asymmetry was examined in several mouse strains. Mixed leukocyte reaction, natural killer cell activity, cytotoxic T lymphocyte response and lymphoproliferation in response to mitogens were investigated in animals with left or right paw preference. From the 7 strains and substrains examined, it appeared that differences in immune function between left and right pawed mice, when present, vary in directionality. Thus, in C3H/HeJ and 129/J, left pawed mice had higher immune responses than right pawed mice, whereas in C3H/HeNCr MTV- and BALB/cJ animals, the reverse was found. In C3H/HeNCr MTV+, C57BL/6J and Collin's heterogenous control population for the high/low asymmetry lines, no differences between animals with left or right paw preference were found. The statistical significance of these differences were not uniform for all the immune parameters studied. These data indicate that the association between immune function and preference for using the left versus right paw is a strain-dependent phenomenon and may suggest that the inconsistent evidence for an association between immune deficiency and left-handedness could be due to genetic heterogeneity among subpopulations.

Animals↗
PubMed1990

Morphine-induced immune alterations in vivo.

The high incidence of human immunodeficiency virus (HIV) seropositivity among drug abusers prompted us to examine in an animal model the effects of morphine on aspects of the immune system that may be specifically related to HIV infection. We now report a robust, sustained elevation in the ratio of CD4+/CD8+ cells in the spleen and thymus of mice chronically treated with morphine. Since CD4+ cells have been reported to be target cells for HIV, these alterations, in concert with a marked cellular atrophy that appears to be restricted to organs of the immune system, suggest that opiates may serve as cofactors in altering the immune status of the host and thus contribute to the increased susceptibility to HIV infection and eventual development of AIDS in opiate abusers.

Animals↗
PubMed1990

Characterization of human B cell (DK) and promonocyte (U937) clones after HIV-1 exposure: accumulation of viral reverse transcriptase activity in cells and early syncytia induction against SupT1 cells.

The kinetics of HIV-1 infection were compared among human B (DK), promonocyte (U937), T-B hybrid (CEMX174), and T (H9) cell lines. Just like H9 cells, CEMX174 cells exhibited strong syncytia induction capacity against highly HIV-1-sensitive CD4+ T cells (SupT1) and had high reverse transcriptase (RT) release in the supernatant. DK and U937 cells showed syncytia induction capacity by 72 hr, but RT activity in the culture supernatant (extracellular RT) increased much later. RT activity in cell lysates (intracellular RT) became detectable at 12-15 days. The inverted extracellular/intracellular RT ratio and syncytia induction capacity were also observed in chronically infected DK (DK-IIIB) and U937 (U937-IIIB) cell lines and subclones from U937-IIIB. Further, the coculture of H9 with DK-IIIB (which indicates no detectable extracellular RT release) showed remarkable amplification of extracellular RT with significant increase of T-B double marker hybrids (H9-DK-IIIB). Our results suggest that B cells and/or monocytes/macrophages may acquire fusing capacity against CD4+ T cells in early stages of the infection and that these cell-to-cell interactions may also lead to a reduction in the number of CD4+ T cells. Further, these T-B and T monocyte hybrids may serve as temporal sites for viral replication. These in vitro studies may provide clues to the possible immunopathological roles of HIV-1-infected B cells and monocytes/macrophages and may help in understanding the mechanisms of viral burden on an infected host.

B-Lymphocytes↗
PubMed1990

Structure-neurotoxicity trends of analogues of 1-methyl-4-phenylpyridinium (MPP+), the cytotoxic metabolite of the dopaminergic neurotoxin MPTP.

The dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) derives from its metabolism to 1-methyl-4-phenyl-pyridinium cation (MPP+), which is then selectively accumulated in dopaminergic neurons. In an effort to assess the structural requirements governing MPP+ cytotoxicity, we evaluated dopaminergic toxicity of MPP+ analogues 3 weeks after their microinfusion into rat substantia nigra. We also evaluated the substrate suitability of MPP+ analogues for high-affinity dopamine uptake in striatal synaptosomes by measuring their ability to induce specific dopamine release. The intranigral neurotoxicity of MPP+ analogues in vivo correlates mainly with their in vitro inhibitory activity on mitochondrial respiration, consistent with a compromise in cellular energy production as the principal mechanism of MPTP-induced cell death. This study extends the structure-neurotoxicity data base beyond that obtainable using MPTP analogues, since many of these are not metabolized to pyridinium compounds. Such information is crucial to assess which possible endogenous or exogenous compounds may exert MPTP/MPP(+)-like toxicity.

1-Methyl-4-phenylpyridinium↗
PubMed1990

Immunoenhancing effects of alprazolam in mice.

The GABA/benzodiazepine receptor chloride channel complex has been proposed to play a modulatory role in immune function. The effects of alprazolam, a triazolobenzodiazepine with high affinity for "central" benzodiazepine receptors, were examined on several parameters of immune function in mice. Natural killer cell activity, mixed leukocyte reactivity and mitogen-induced lymphocyte proliferation were all significantly increased two hr after administration of low doses (0.02-1.0 mg/kg) of alprazolam. Twenty four hr later, similar but less robust immunoenhancing effects were observed. Higher doses of alprazolam (5-10 mg/kg) did not affect these measures of immune function. The immunoenhancing effects of alprazolam did not appear related to corticosterone levels. In contrast, vehicle injection caused a profound suppression of these immune parameters two hr later, which was no longer apparent 24 hr later. This immunosuppression appeared to correlate with a concurrent rise in serum corticosterone levels. These data support the hypothesis that the GABA/benzodiazepine receptor chloride channel complex modulates immune function. Use of low doses of alprazolam may be of potential clinical importance when immunoenhancement is required.

Adjuvants, Immunologic↗
PubMed1990

Differential immune responsiveness in mouse lines selectively bred for high and low sensitivity to ethanol.

Natural killer cell activity was compared in the Long-Sleep and Short-Sleep mouse lines. These mice, initially selected for their sensitivities to a hypnotic dose of ethanol, are also differentially sensitive to other agents which act through the benzodiazepine/GABA receptor chloride ionophore complex. Natural killer cell activity was 40-59% lower in Short-Sleep when compared to Long-Sleep mice. Flow cytofluorometric analysis demonstrated that the number of Nk-1+ cells was also lower in the spleens of Short-Sleep than Long-Sleep mice. In addition, the incidence of 3-methylcholanthrene-induced tumors was significantly greater in Short-Sleep (85.7%) than in Long-Sleep (14.3%) mice. These results suggest that the Long-Sleep and Short-Sleep mouse lines may represent a unique model to assess the physiological role of the benzodiazepine/GABA receptor chloride ionophore complex in the neural modulation of immune function.

Animals↗
PubMed1990

Immune function in lines of mice selected for high or low degrees of behavioral asymmetry.

Cerebral lateralization has been suggested to play a regulatory role in immune function. In this study, several measures of immune function were evaluated in mice selectively bred for either a strong (HI) or weak (LO) degree of behavioral asymmetry (paw preference) and compared to an unselected control population (HET). Both HI and LO animals had fewer spleen cells but higher degrees of [3H]thymidine incorporation into DNA (on a per cell basis) than HET mice. However, only HI mice had lower immune functions compared to HET controls manifest as reduced mixed leukocyte reaction (MLR), cytotoxic T lymphocyte (CTL) activity, and natural killer (NK) cell activity. These findings indicate that although both extremes in the degree of paw preference may be associated with deviations from the norm, a high degree of behavioral lateralization is associated with decreased immune responsiveness in this animal model.

Animals↗
PubMed1990

Opiate-induced inhibition of calcium flux in immune cells.

Administration of morphine as a subcutaneous implant inhibits the initial influx of calcium (Ca2+) induced by mitogens in mouse splenocytes. This effect was not reproduced by incubation of splenocytes with morphine (10(-8)-10(-4)M). Within T cell subpopulations, CD4+, but not CD8+ cells were affected. Adrenalectomy abolished this effect of morphine in CD4+ but not B cells. Moreover, simultaneous administration of the opiate antagonist naltrexone blocked the effect of morphine in B cells, but not in CD4+ cells. These data indicate that inhibition of Ca2+ influx by morphine may be mediated through distinct glucocorticoid-dependent and independent mechanisms. The morphine-induced inhibition of Ca2+ influx in immune cells reported here may be an early event mediating opiate-induced immunosuppression.

Adrenalectomy↗
PubMed1990

Spontaneous rupture of the stomach.

Spontaneous rupture of the stomach is a rare but rapidly fatal accident. In the reported case, the galloping pace of deterioration claimed the life of the patient in spite of timely institution of resuscitative measures. However, in less catastrophic forms, provided the condition is recognised by its characteristic features, it is possible to improve the prognosis by expeditious surgical correction. It behoves us to briefly review the clinical features of this condition while presenting the case report.

Adult↗
PubMed1989

Evaluation of the effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA) on HIV-1 production in vitro.

Effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), an inhibitor of the common Adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4.), on HIV-1 production was evaluated in vitro. Reverse transcriptase (RT) activity in the supernatant was inhibited by nearly 50% in EHNA-treated HIV-1 infected H9 cells, when compared with untreated but infected H9 cells. There was also a significant decrease in cell viability, but this was reversed following the addition of deoxycytidine (dC) to these cultures. The combined treatment was also effective in suppressing HIV-1 release from HIV-1-infected U937 cells. This combined EHNA plus dC treatment had no effect on RT activity in the cell lysates, suggesting that the inhibition of HIV-1 production may be due to the disturbance of virus release from infected cells.

Adenine↗
PubMed1989

Suppression of natural killer cell activity by FG 7142, a benzodiazepine receptor "inverse agonist".

A dose-dependent (5-50 mg/kg) suppression of natural killer (NK) cell activity was observed 2 h after administration of the benzodiazepine receptor "inverse agonist" FG 7142 (N-methyl-beta-carboline-3-carboxamide), and was still manifest 24 h later. Addition of FG 7142 (1-1000 nM) to the 4 h 51 Cr release assay did not affect NK cell activity. Pretreatment of mice with the benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg) blocked FG 7142-induced suppression of NK cell activity, but had no effect when administered alone. The suppression of NK cell activity by FG 7142, a compound which produces a syndrome resembling stress or anxiety in both animals and man, provides further evidence that the central nervous system pathways subserved by the benzodiazepine/GABA receptor chloride channel complex ("supramolecular complex") may play a role in the modulation of immune function.

Animals↗
PubMed1989

Sexual behavior suppresses the primary antibody response in the golden hamster.

The possibility that sexual behavior triggers neural or endocrine events that influence immune function was explored in male Golden Hamsters (Mesocricetus auratus). Sexually experienced males showed a 62.8 and 64.9% decrease in antibody response to TNP-ovalbumin compared to virgin and sham-mated males, respectively, as measured by ELISA. Antibody deficiency was associated with copulation on the day of immunization and was highly correlated with ejaculatory behavior and the incidence of prolonged intromissions, an indicator of sexual satiety. Although a single sexual encounter was not sufficient to inhibit antibody levels, prolonged intromissions were inversely correlated with titers. Changes in antibody production were not related to plasma levels of cortisol, corticosteroid-binding globulin activity, or testosterone. These results suggest that sexual behavior is immunosuppressive and may play a role in the communicability of sexually transmitted diseases.

Animals↗
PubMed1989

Mating suppresses splenic natural killer cell activity in male golden hamsters.

The possibility that sexual behavior is associated with changes in natural killer cell activity was explored using a 4-h chromium-51 release assay. Mated male Golden Hamsters (Mesocricetus auratus) showed a significant suppression of natural killer cell activity 2 h after sexual activity relative to matched Virgin controls. Natural killer cell activity returned to control levels by 16 h postmating. The suppression of natural killer cell activity did not correlate with changes in plasma cortisol, transcortin, or testosterone levels, or with ejaculatory or intromissive behaviors. Administration of 0.40 mg/100 g of testosterone also suppressed natural killer activity at 2 h.

Animals↗
PubMed1989

Production and characterization of T-cell clones specific for trinitrophenyl (TNP)-modified syngeneic spleen cells (TNP-self).

Using serial antigenic challenge as the method of selection and stimulation, continuous lines of cytotoxic T-lymphocytes (CTL) directed against TNBS-modified syngeneic spleen cells (TNP-self) have been generated. Spleen cells from C3H/HeJ (H-2k) mice were primed in vitro with autologous spleen cells modified with TNBS, and subsequently cloned by limiting dilution and in soft agar in the presence of IL2. These CTL clones grew continuously in medium supplemented with IL2 and in the presence of antigen. They are antigen specific and H-2 restricted in their target cell recognition. They all express Thyl and Lyt2 surface markers. None of the clones exhibit natural killer (NK) cell activity. All CTL clones tested so far are restricted in their target cell recognition to H-2Kk-TNP and none were found to be restricted to H-2Dk-TNP. These findings demonstrate at the clonal level the H-2K/D restriction of TNP-self specific CTL. These clones provide tools that may facilitate an understanding of the development and regulation of antigen specific CTL. They may also serve as models useful towards an understanding of the mechanism of lysis by CTL.

Animals↗
PubMed1989

Linear scleroderma. A unique presentation.

A rare case of linear scleroderma with plaques of morphea in hemicorporeal distribution and subclinical systemic involvement is presented. Its possibility of progression into systemic sclerosis, which has not been reported earlier, is discussed.

Adult↗