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P K Arora

Publications and source records attributed to P K Arora.

61 records · Page 4Linked to original sources

Host-parasite relationships in experimental airborne tuberculosis. V. Lack of hematogenous dissemination of Mycobacterium tuberculosis to the lungs in animals vaccinated with Bacille Calmette-Guérin.

The influence of bacille Calmette-Guérin (BCG) on the pathogenesis of experimental airborne tuberculosis was studied. In a model that approximates the conditions under which man is vaccinated and infected, BCG-vaccinated and unvaccinated guinea pigs were infected by the respiratory route with an inoculum that resulted in the inhalation and retention (by each animal) of approximately three virulent tubercle bacilli (Mycobacterium tuberculosis strain H37Rv). Hematogenous seeding of the lungs occurred in unvaccinated animals about three weeks after aerosol infection but did not occur in BCG-vaccinated animals. Furthermore, the lungs of BCG-vaccinated animals failed to kill H37Rv that was introduced intravenously; however, evidence of mycobacteriostatic activity was found throughout the lungs. In view of the importance of hematogenous dissemination to the apex of the lungs in the establishment of pulmonary tuberculosis in man, the foregoing observations suggest a means by which vaccination with BCG may confer acquired resistance to tuberculosis.

Animals↗

Suppression of cytotoxic T lymphocyte (CTL) activity by FG 7142, a benzodiazepine receptor 'inverse agonist'.

A dose-dependent (12.5-100 mg/kg) suppression of cytotoxic T lymphocyte (CTL) activity was observed in mice after administration of the benzodiazepine receptor 'inverse agonist' FG 7142 (N-methyl-beta-carboline-3-carboxamide). This compound produces a syndrome resembling stress or anxiety in both animals and man. Addition of FG 7142 (1-1000 nM) to either a 4-hour 51Chromium-release assay or 5-day in vitro CTL generation system did not affect CTL activity. Pretreatment with the benzodiazepine receptor antagonist Ro 15-1788 (10 mg/kg) attenuated FG 7142-induced suppression of CTL activity, but had no effect when administered alone. Time-course studies indicated that FG 7142-induced suppression of CTL activity was long-lasting. The suppression of CTL activity by FG 7142 provides further evidence that the central nervous system pathways subserved by the benzodiazepine/GABA receptor chloride channel complex may play an important role in the modulation of immune function.

Animals↗

Pyrrole formation from 4-hydroxynonenal and primary amines.

The reaction of trans-4-hydroxy-2-nonenal (4-HNE) with primary amines was investigated to elucidate chemistry that may clarify the nature of its physiological covalent binding with protein-based primary amino groups. Such binding of 4-HNE, generated endogenously from lipid peroxidation, appears to be a pathophysiologic factor in the modification of low-density lipoprotein and perhaps other instances. We now show that 4-HNE reacts with primary amines in aqueous acetonitrile at pH 7.8 to afford after workup, in 14-23% yield, the corresponding pyrroles, which were characterized by independent synthesis from 4-oxononanal. Additional, mostly unstable adducts are also formed, some of which eventually "age" to the pyrrole. Hydride reduction after initial adduct formation permits the isolation of more stable materials, one of which has been identified as the reduced amine Michael addition product. Pyrrole formation may constitute a physiologically important reaction of 4-hydroxyalkenals.

Aldehydes↗

Strain variation in immune response and behavior following the death of cage cohorts.

Strain differences in both immune function and behavior were observed following exposure of mice to the death of cage-cohorts. AKR/J, BALB/cN, and C3H/HeJ mice were exposed to a dead cohort for two hours at 48 hour intervals for 30 days. During this two hour period, AKR/J mice displayed intense fighting and mounting behavior. In addition, these mice attacked, cannibalized, and buried carcasses. Neither C3H/HeJ nor BALB/cN mice exhibited the complete repertoire of behaviors directed at either carcasses or cage-cohorts observed in AKR/J mice. After 15 exposures to the death of cage-cohorts, allogeneic cytotoxic T-lymphocyte (CTL) response was suppressed in AKR/J mice, but was enhanced or unchanged in C3H/HeJ and BALB/cN mice, respectively. Other immune parameters including natural killer (NK) cell activity, and lipopolysaccharide-stimulated B cell proliferation were unchanged in AKR/J mice but increased in BALB/cN mice exposed to the death of cage-cohorts for thirty days. These results suggest: 1) that both suppression of the CTL response and behaviors indicative of defensive burying in AKR/J mice may specifically be due to the loss of cage-cohorts, since they were not observed following exposure of these mice to the death of contraspecific animals; and 2) that both the behavioral repertoire and immune responses following exposure to the death of cage-cohorts may be strain dependent. This strain dependence may reflect differences in the ability to cope with the intermittent presentation of a stressor, and may explain, at least in part, variability in stress-induced changes in immune functions.

Agonistic Behavior↗