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Biomedical subjects

T Schwartz

Publications and source records attributed to T Schwartz.

At least 55 records · Page 3Linked to original sources

Phorbol esters inhibit insulin-induced receptor down-regulation in cultured human lymphocytes: association with diminished insulin receptor autophosphorylation.

Exposure of cells to phorbol 12-myristate 13-acetate (PMA) has been reported to result in resistance to the acute biological effects of insulin and an associated reduction in insulin-receptor tyrosine kinase activity. To investigate the relationship of insulin receptor autophosphorylation with a longer-term action of insulin the effect of PMA on insulin-stimulated receptor down-regulation was examined in cultured human lymphocytes (IM-9). Lymphocytes bound [3H]phorbol dibutyrate specifically with characteristics typical of binding to protein kinase C (PKC). Acute exposure (30 min) to PMA resulted in a transient decrease of insulin binding which is consistent with a decrease in receptor number. Chronic (18 h) exposure to PMA (5 nM) resulted in inhibition of insulin-induced down-regulation of its cognate receptor. Sphingosine, an inhibitor of PKC, or chronic pre-exposure to a high concentration of PMA (1 microM), which is known to inactivate PKC, blocked the effect of PMA. PMA inhibited insulin-stimulated receptor internalization by 26% and receptor degradation by 82%. Exposure of intact cells to PMA followed by insulin treatment inhibited insulin-receptor autophosphorylation subsequently assayed in vitro, as well as beta-subunit tyrosine phosphorylation in situ. In summary, PMA inhibited insulin-stimulated receptor down-regulation via activation of PKC. This was associated with an inhibition of both receptor internalization and receptor degradation. There was a concomitant inhibition of receptor tyrosine autophosphorylation consistent with a requirement of receptor kinase activation for both short-term and long-term biological effects of insulin.

Cell Line↗

Site-directed and transposon-mediated mutagenesis with pfd-plasmids by electroporation of Erwinia amylovora and Escherichia coli cells.

The suicide plasmid pfdA31-Tn5 was constructed to mutagenize Erwinia amylovora and Escherichia coli strains by electorporation. This vector carries the bacteriophage fd replication origin, a beta-lactamase gene and the transposon Tn5. For propagation the plasmid depends on host cells producing fd gene-2 protein. Electroporation of E.amylovora or E.coli cells with plasmid pfdA31-Tn5 yielded more than 10(4) transposition events per micrograms DNA. We have produced and characterized transposon mutants of E.amylovora affecting either galactose metabolism or the synthesis of the phytotoxin (L)-2,5-dihydrophenylalanine. A Tn5-insertion in a gene, involved in exopolysaccharide synthesis of E.amylovora strain Ea7/74, was subcloned into vector pfdA31 and used to mutagenize E.amylovora strain Ea1/79 by site-directed recombination.

Blotting, Southern↗

Anaesthesia and the child with HIV infection.

The frequency of AIDS in the paediatric population is growing rapidly and is expected to get worse. The anaesthetist will participate in the care of these children in the operating room and the intensive care unit with increasing frequency and must therefore have an understanding of the many manifestations of this syndrome. Children become infected with HIV by transplacental transmission from mother to fetus in over 80% of cases. Early diagnosis in infants can be very difficult. Clinical manifestations of HIV infection in children result from damage to almost every organ system. Considerations for the anaesthetist include: the effects of medications, cardiovascular dysfunction, pulmonary disease, altered metabolism, equipment preparation, choice of anaesthetic, modes of viral transmission and psycho-social issues.

Anesthesia↗

Haptoglobin typing in canine bloods.

Haptoglobin typing by vertical electrophoresis in a discontinuous polyacrylamide gel was conducted on 47 dog blood samples, of which 19 were from Doberman pinschers, 20 from German shepherds, and 8 from pit bullterriers. Two phenotypes were common in the three breeds and could not be used to differentiate between them. Canine haptoglobin phenotypes were, however, sufficiently different from those of humans to warrant using haptoglobin typing as a method for determining the origin of bloodstains.

Animals↗

The persistence of neutralizing antibodies after revaccination against smallpox.

Persistence of neutralizing antibodies after revaccination against smallpox was studied. Single serum samples from 140 revaccinated donors were tested for neutralizing antibodies using the plaque reduction assay. The donors, aged 21-49 years at sampling, had been vaccinated in infancy and revaccinated at 8 and 18 years; they formed seven groups of 20 men each, revaccinated about 3, 5, 10, 15, 20, 25, and 30 years before sampling. The differences in mean titer among groups were insignificant (P greater than .01). The titer significantly decreased during the first 3 years after the revaccination but remained stable for at least 30 years thereafter (geometric mean titer, 10.5; 95% confidence interval, 6.8-16.4). The results suggest that there is probably no need for routine revaccinations beyond the primary and two revaccinations; nevertheless, persons at high risk should be revaccinated regardless of their vaccination status.

Adult↗

Neuropeptide degradation by large vessel and microvessel-derived endothelial cells in vitro: cell surface catabolism of thyrotropin releasing hormone (TRH).

Cell surface ectopeptidase activity of purified, cultured large vessel and microvessel-derived endothelial cells (EC) was studied. Degradation of thyrotropin releasing hormone (TRH), and production of cyclo-His-Pro was significantly increased (P less than 0.001) in large vessel EC compared with microcapillary EC. Since the rate of catabolism in the microvascular capillary bed is 5 times less than that in the large vessel wall, peptide concentrations are likely maintained longer in close proximity to their site of biosynthesis, where they are presumably most active.

Aminopeptidases↗

Blood pressure, catecholamines, and pancreatic polypeptide in obstructive sleep apnea with and without nasal Continuous Positive Airway Pressure (nCPAP) treatment.

In order to study blood pressure, adrenergic, and cholinergic activity in severe obstructive sleep apnea (OSA), 14 patients with apnea index (AI) greater than 30 apneas/h, mean apnea time index greater than 20 sec were studied before and with nasal Continuous Positive Airway Pressure (nCPAP). Sleep, respiration, arterial blood pressure, arterial plasma catecholamines [norepinephrine (NE) and epinephrine (E)], and plasma pancreatic polypeptide (PP) were measured without and after seven days treatment with nCPAP. Initially in the apnea, arterial blood pressure decreases, and thereafter steadily increases and shows a maximum during the first breath terminating the apnea. With nCPAP the arterial pressure variations disappeared. Awake morning systolic (SBP) and diastolic (DBP) blood pressure decreased the nCPAP treatment. A significant relation between the reduction in AI and the reduction in morning awake SBP and DBP with nCPAP treatment was observed. No significant changes in NE were observed with nCPAP treatment. Epinephrine decreased and PP increased significantly with nasal nCPAP treatment. The systolic and diastolic blood pressure reduction was significantly related to the decrease in E and the increase in PP. No association between sleep stages and plasma NE, E, and plasma-PP was found before treatment. With nCPAP treatment plasma-PP was higher during non-rapid eye movement (NREM) stage 2 to 4 sleep than during rapid eye movement (REM) sleep. Thus, morning awake arterial blood pressure and nocturnal arterial blood pressure decrease with nCPAP treatment in sleep apnea patients. These hemodynamic changes are related to the decrease in AI and sympathetic activity and the increase in parasympathetic activity.

Adult↗

Infectious disease among Ethiopian immigrants in Israel.

From 1980 to 1985, 14,465 refugees arrived in Israel from Ethiopia. Typhoid fever, tuberculosis, or malaria was present in 1.8% to 9% of immigrants; as many as 93% were infested with intestinal parasites. Extreme malnutrition was common, and serologic evidence of syphilis and hepatitis B was frequently encountered. A program for diagnosis, therapy, and immunoprophylaxis following the massive influx of African refugees is described.

Adolescent↗

Effect of ganglionic blockade on endogenous circulating pancreatic polypeptide, vasoactive intestinal polypeptide, substance P, neurotensin and noradrenaline in healthy controls and long-term insulin-dependent diabetic patients.

Plasma pancreatic polypeptide (PP), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT) and noradrenaline (NA) were measured in eight healthy subjects and 12 long-term insulin-dependent diabetic patients with and without autonomic neuropathy, before and after intravenous infusion of the ganglionic blocking agent trimethaphan camsylate, in order to determine the influence of the autonomic nervous system on the baseline values of the substances. The basal levels of the measured substances were not significantly different in healthy subjects and patients with or without diabetic autonomic neuropathy. In healthy subjects, the ganglionic blockade induced a significant decrease in PP (80%) (P less than 0.02), NA (58%) (P less than 0.05), NT (27%) (P less than 0.05) and a significant increase in SP (30%) (P less than 0.05), while the VIP concentration remained unchanged. The diabetic patients had nearly the same significant decrease in PP (68%) (P less than 0.01), NA (50%) (P less than 0.01), NT (22%) (P less than 0.02), VIP (21%) (P less than 0.05) and increase in SP (73%) (P less than 0.01). No relationship was found between the autonomic neuropathy and changes of the substances during ganglionic blockade. The results indicate that the postganglionic part of the autonomic nervous system participates in the maintenance of a normal baseline level of PP, NT and NA, but not of VIP. The regulation of VIP may be disturbed in long-term diabetic subjects.

Adult↗

[Comparative studies on the rotavirus syndrome following infection with human rotavirus of the subgroup 1 or 2].

Human rotavirus infection which heals spontaneously causes gastroenteritis in newborns and infants. 150 pediatric patients infected with rotavirus as diagnosed by ELISA suffered from diarrhoea for an average of 3 days, from vomiting for 1 day, and/or fever for 1-2 days. Nowadays this disease is known as "human rotavirus syndrome". Human rotaviruses can be divided into at least 4 serotype antigens and some 3 further subgroup antigens. The serotype antigens are only detectable biologically (e.g. by neutralization test), whereas the subgroup antigens can be demonstrated as specific proteins by a solid-phase test (ELISA). This study investigated whether an infection with human rotavirus of subgroup 1 (21%) or 2 (77%), which occur most frequently causes different degrees of severity of the rotavirus syndrome. The clinical comparison of 27 (subgroup 1) and 98 (subgroup 2) infected patients shows that the disease is not significantly different. This means that the detection of subgroup antigens 1 and 2 does not result in a different prognosis for the disease. The diagnosis of subgroup antigens after human rotavirus infection is therefore clinically important only for the detection of nosocomial infections, especially due to the rarely occurring subgroups 1 and 3.

Antigens, Viral↗

Metabolism of C-peptide in the dog. In vivo demonstration of the absence of hepatic extraction.

The in vivo hepatic metabolism of connecting peptide (C-peptide) in relation to that of insulin has not been adequately characterized. A radioimmunoassay for dog C-peptide was therefore developed and its metabolism studied in conscious mongrel dogs, with sampling catheters chronically implanted in their portal and hepatic veins and femoral artery. The hepatic extraction of endogenous C-peptide under basal conditions was negligible (4.3 +/- 4.5%) and was similar to the hepatic extraction of C-peptide measured during the constant exogenous infusion of C-peptide isolated from dog pancreas. Simultaneously measured hepatic extraction of endogenous and exogenously infused insulin were 43.8 +/- 7.6 and 47.5 +/- 4.4%, respectively. The metabolic clearance rate of infused C-peptide was 11.5 +/- 0.8 ml/kg per min and was constant over the concentration range usually encountered under physiological conditions. In additional experiments, the effect of parenteral glucose administration on the hepatic extraction of C-peptide and insulin was investigated. The hepatic extraction of C-peptide (6.2 +/- 4.0%) was again negligible in comparison with that of insulin (46.7 +/- 3.4%). Parenteral glucose administration did not affect the hepatic extraction of either peptide irrespective of whether it was infused peripherally, intraportally, or together with an intraportal infusion of gastrointestinal inhibitory polypeptide. The fasting C-peptide insulin molar ratio in both the portal vein (1.2 +/- 0.1) and femoral artery (2.1 +/- 0.3) was also unaffected by the glucose stimulus. These results therefore indicate that, since the hepatic extraction of C-peptide is negligible and its clearance kinetics linear, the peripheral C-peptide concentration should accurately reflect the rate of insulin secretion. New approaches to the quantitation of hepatic extraction and secretion of insulin by noninvasive techniques are now feasible.

Animals↗