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Biomedical subjects

H Steinberg

Publications and source records attributed to H Steinberg.

At least 19 recordsLinked to original sources
PubMed1992

Drug interactions represented by high resolution computer graphics.

The amount of backward walking induced in mice by co-administration of clenbuterol, a beta-adrenoceptor agonist and putative antidepressant, and the benzodiazepine chlordiazepoxide was plotted as a three-dimensional surface, using modified Uniras software. The surface was compared with the theoretical surface to be expected if the interactions between the two drugs were merely additive. The difference between the theoretical and the obtained surfaces was plotted and a functional representation of statistical variability was 'draped' over the difference model. The computer methods can be applied to small amounts of irregularly distributed data, and results are apparent from simple inspection, e.g. the highest peak of backward walking is also the most reliable statistically. The technique is useful for both laboratory and clinical studies.

Animals↗
PubMed1992

Erythropoietin response to acute normobaric hypoxia in humans.

Hypoxia causes an increased production of erythropoietin (EPO), but the time course of the EPO response in humans has not been well characterized. This study examines the relationship between the duration of normobaric hypoxic exposure and plasma EPO levels in healthy human subjects. Six volunteers breathed a gas mixture of 10.5% O2-89.5% N2 continuously for 5, 60, and 120 or intermittently for 240 min. O2 saturations were maintained between 75 and 85% during the exposure. Arterial pH was 7.467 +/- 0.019, PO2 37.05 +/- 2.43 Torr, and PCO2 36.69 +/- 2.05 Torr. O2 half-saturation pressures of hemoglobin were normal for all subjects. Plasma EPO was measured every 30 min for 360 min by radioimmunoassay. No increase in EPO was seen after the 5- and 60-min exposures. However, a 50% increase was seen 240 min after the initiation of the 120-min hypoxic exposure (P less than 0.01). Intermittent exposure resulted in an increase of EPO by 52% 360 min after the onset of exposure (P less than 0.05). Therefore, exposing humans continuously to an inspiratory O2 fraction of 0.105 for 120 min or intermittently for 240 min provides a sufficient stimulus to increase production of EPO.

Adult↗
PubMed1992

Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six.

Animals↗
PubMed1991

Cyclosporin A modulates the course of woodchuck hepatitis virus infection and induces chronicity.

Immunosuppression is known to influence the state of chronic hepatitis B virus infection, and is thought to increase the risk of developing chronic infection in newly exposed individuals. Cyclosporin A (CsA), an immunosuppressive agent that inhibits Th cell function, was administered to woodchucks chronically infected with woodchuck hepatitis virus (WHV), and resulted in a decreased severity of chronic hepatitis and an increased viremia during the treatment. Adult woodchucks inoculated with WHV and given CsA for 14 wk had increased viremias, decreased acute phase liver injury, and developed chronic infections at a higher rate compared with immunocompetent woodchucks given virus alone (chronicity in seven of seven WHV + CsA + vs zero of nine WHV + CsA-; p less than 0.001). These results in a relevant animal model of hepatitis B virus infection indicate: 1) that liver injury in acute hepadnavirus infections is immune-mediated and not a direct cytopathic effect of virus replication; 2) that Th cells function in the inflammatory response and in the immunologic control of hepadnavirus infection; and 3) that suppression of Th cell function in acute hepadnavirus infection decreases liver injury but alters the outcome of infection in favor of chronicity. These results also suggest continued challenges in the application of CsA in liver transplantation for hepatitis B virus-induced diseases.

Acute Disease↗
PubMed1990

Effects of temporary withdrawal from regular running.

Forty regular male runners were divided into two similar groups and studied for six weeks. One group continued normal running, but the other stopped running for the middle two weeks of the study. Questionnaires were completed at the end of each week. Symptoms of depression were greater in the withdrawn than in the control group at the end of the second week of withdrawal. Somatic symptoms, anxiety, insomnia and feelings of being under strain were greater in the withdrawn group after both the first and second weeks of withdrawal. The groups did not differ in the final two weeks, when running had been resumed. These effects strengthen the view that stopping regular physical exercise produces a 'withdrawal syndrome', and that exercise might therefore be regarded as addictive. The increase in depression may reflect a more gradual loss of the antidepressive effect of exercise training.

Adaptation, Psychological↗
PubMed1990

Besnoitiosis of the reproductive tract of a Blue Duiker (Cephalophus monticola).

A mature male Blue Duiker that had been born in the United States was submitted for necropsy examination following a brief illness. On histologic examination of the reproductive tract several Besnoitia cysts were found in the epididymis, prostate and bulbourethral gland. The lack of an inflammatory response or any negative effect on fertility, based on histologic evaluation and breeding history, is in contrast with the severe orchitis, epididymitis and infertility of besnoitiosis in cattle. This is the first report of an autochthonous infection of Besnoitia in the United States as well as the first report of besnoitiosis in a Blue Duiker.

Animals↗
PubMed1990

Endogenous opioids modulate the cardiovascular response to mental stress.

The role of endogenous opioids in the cardiovascular response to mental stress was investigated in two controlled studies. In the first, cardiovascular, hormonal and psychological measures were made in a group of subjects before, during and after presentation of either a mental stress task or a non-stressful control task in the presence of naloxone (8 mg), an opiate antagonist, or an equal volume of saline. The study was carried out in random order and single(subject)-blind. Naloxone specifically enhanced the heart rate response to the stressful task but had no effect on blood pressure, plasma epinephrine or norepinephrine, or feelings of anxiety. Naloxone increased plasma cortisol and ACTH in both stressful and control tasks. A second, double-blind, study replicated the effect on heart rate. An endogenous opioid mechanism thus appears to inhibit the cardiovascular response to stress.

Adolescent↗
PubMed1990

Mapping and interpreting complex interactions between psychoactive drugs by simple computer-generated models.

Drug combinations often yield results not readily predictable from those of their separate constituents. Computer programs have been developed to generate models of dual drug effects to analyse the results of experiments involving drug combinations. Single and combined dose-response results of rat locomotor activity are expressed as three-dimensional models. A manually plotted isobol diagram, showing eqi-active dose combinations of amylobarbitone and dexamphetamine, is compared with isobols constructed by the computer. A simple dose model theory is proposed which assumes that the two drugs have merely additive effects; differences between expectations from this theoretical model and the experimental results actually obtained were found by the computer. This computer approach allows detailed analysis of results. Three-dimensional dose response surfaces can provide a simple visual guide to dose combinations whose effects deviate significantly from those expected if the constituents were simply additive. Areas of special interest can thus be highlighted.

Animals↗
PubMed1990

Natural history of experimental woodchuck hepatitis virus infection: molecular virologic features of the pancreas, kidney, ovary, and testis.

The kinetic patterns of woodchuck hepatitis virus (WHV) infection were monitored in the pancreas, kidneys, ovaries, and testes. Groups of woodchucks experimentally infected with a standardized inoculum of WHV were sacrificed at different times over a 65-week period beginning in the preacute phase of viral infection and continuing to the period of serologic recovery or the establishment of chronic infections and subsequent hepatocellular carcinoma (B. E. Korba, P. J. Cote, F. V. Wells, B. Baldwin, H. Popper, R. H. Purcell, B. C. Tennant, and J. L. Gerin, J. Virol. 63:1360-1370, 1989). Tissues from an additional group of long-term (2 to 3 years) chronic WHV carriers which had been infected with the same WHV inocula were also examined. Viral DNA replication intermediates were found in all four tissues during the acute phase of WHV infection. However, WHV DNA replication intermediates were observed only in the kidneys of a small proportion of the chronically infected animals. Following the acute phase of infection, WHV DNA was present only in the pancreas, kidneys, and ovaries of the chronically infected woodchucks. A progressive evolution of different WHV genomic forms related to the replicative state of WHV was observed in these tissues. Histologic evaluation of these four tissues revealed only minimal, localized lesions which were not correlated with the state of WHV activity. The observations compiled in this study further extend the tissue tropism of WHV.

Animals↗