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Biomedical subjects

R Cohen

Publications and source records attributed to R Cohen.

At least 487 records · Page 27Linked to original sources
PubMed1984

Biosynthetic human insulin and proinsulin have additive but not synergistic effects on total body glucose disposal.

Recent studies from our laboratory have demonstrated that human biosynthetic proinsulin has a much slower MCR than insulin as well as a greater effect on hepatic than on peripheral tissues. Since both of these features make proinsulin potentially useful as an adjunct to insulin, the present study was undertaken to characterize the biological effects of combined infusions of insulin and proinsulin. As an initial study, multiple euglycemic clamp studies were performed in six normal subjects to construct dose-response curves for insulin- and proinsulin-mediated glucose disposal. Insulin infusion rates of 0.63, 1.67, 5, and 10 micrograms/M2 X min were compared to proinsulin infusion rates of 2.75, 7.5, 22.5, and 45 micrograms/M2 X min. Analysis of these dose-response curves indicated that proinsulin-mediated glucose disposal was approximately 7% that of insulin. Each subject also received a combined infusion of insulin (0.63 micrograms/M2 X min) and proinsulin (2.75 micrograms/M2 X min). The mean (+/- SE) glucose disposal rate obtained during the combination study (319 +/- 21 mg/M2 X min) was similar to that predicted by adding the results from the individual hormone infusions (307 +/- 21 mg/M2 X min). Analysis of the dose-response curves for insulin and proinsulin was also useful in predicting the glucose disposal rate during the combination study (290 +/- 19 mg/M2 X min). Thus, using either approach to predict the glucose disposal rates, insulin and proinsulin appeared to have additive effects on total body glucose disposal.

Adult↗
PubMed1984

Glucose metabolism in experimental hyperthyroidism: intact in vivo sensitivity to insulin with abnormal binding and increased glucose turnover.

The characteristics of the dose response of insulin on the glucose turnover rate and erythrocyte insulin binding parameters were determined in five normal men before and during experimentally induced hyperthyroidism [L-T4 (2 micrograms kg-1 day-1) for 4 weeks with additional L-T3 (1 microgram kg-1 day-1) for the following 3 weeks]. Hyperthyroidism was characterized by significant rises in T3 from 1.92 +/- 0.17 (+/- SEM) to 3.66 +/- 0.17 nmol/liter (P less than 0.01) and resting metabolic rate from 39 +/- 0.7 to 48 +/- 1 watt/m2 (P less than 0.001). While the subjects received a diet adapted to the metabolic rate, blood glucose rose from 3.8 +/- 0.07 to 4.46 +/- 0.11 mmol/liter (P less than 0.05) without a significant change in plasma insulin. During the insulin dose-response study, glucose infusion rates were unaltered by hyperthyroidism, and neither the maximum effect nor the sensitivity to insulin was altered. Glucose turnover rate, measured using [6,6-2H2]glucose as tracer, was determined in the basal state and during the 0.4 mU kg-1 min-1 insulin infusion. In the basal state, it was significantly increased by hyperthyroidism (control, 2.3 +/- 0.1; hyperthyroidism, 3.7 +/- 0.1 mg kg-1 min-1). During the insulin infusion, hepatic glucose production was totally suppressed before T4 and T3 treatment, but was 0.96 +/- 0.39 mg kg-1 min-1 during T4 and T3 treatment. A marked decrease in the insulin binding affinity to erythrocytes was found without a change in the insulin receptor number. In conclusion, glucose metabolism in experimental hyperthyroidism is characterized by 1) increases in basal glucose production and utilization; 2) antagonism between the effect of insulin and hyperthyroidism at the hepatic level; and 3) lack of peripheral insulin resistance in spite of marked alteration in erythrocyte insulin binding affinity.

Adult↗
PubMed1984

Effects of human pancreatic tumor growth hormone-releasing hormone (hpGRH1-44-NH2) on immunoreactive and bioactive plasma growth hormone in normal young men.

Synthetic human pancreatic tumor GH-releasing hormone (hpGRH 1-44-NH2) was given by iv bolus injection to 10 normal men at doses of 75, 150, 300, and 600 micrograms. At all doses the plasma GH responses were similar in an individual subject. Among subjects, however, the responses were significantly different, with peak GH concentrations ranging between 9.0 micrograms/liter and 54.9 micrograms/liter. The GH released in response to GRH was bioactive in the Nb2 lymphoma cell multiplication assay. The circulating GH 30 and 60 min after GRH was detected in 3 molecular forms corresponding to little, big, and big-big GH. These forms averaged 50%, 30%, and 20% of the total immunoreactive GH, respectively. The mean rise of plasma somatomedin-C, from 1.86 U/ml to 2.21 U/ml 24 h after GRH, was not statistically significant. A small but statistically significant GRH dose-dependent rise in plasma PRL (mean PRL concentrations 10 min after 600 micrograms GRH, 11.13 micrograms/liter occurred consistently after GRH injection. The evidence that the GH released by GRH is bioactive supports the potential use of GRH for therapeutic applications.

Adult↗
PubMed1984

Epilepsy in prison: elevated prevalence and no relationship to violence.

The epidemiologic, clinical, and social characteristics of epilepsy were investigated in men entering the Illinois prison system and compared with a matched control group of prisoners without epilepsy. The prevalence of epilepsy was 2.4%, four times higher than the prevalence among men aged 20 to 39 in Rochester, MN. Head trauma was the probable cause of epilepsy among 45% of the prisoners with epilepsy, a much higher percentage than that reported in studies of other populations. In comparison with an age- and race-matched group of prisoners without epilepsy, the epilepsy group was not convicted of more serious or more violent crimes.

Adolescent↗
PubMed1984

The effects of biosynthetic human proinsulin on carbohydrate metabolism.

Large quantities of biosynthetic human proinsulin have recently become available through recombinant DNA technology. Since the in vivo effects of human proinsulin have not been studied in man, we compared the dose-response relationship for stimulation of glucose disposal and suppression of hepatic glucose output by proinsulin and insulin. Ten normal subjects were studied using the euglycemic glucose clamp technique. The human proinsulin and insulin infusion rates were chosen to achieve steady-state proinsulin levels 10-fold higher than insulin levels on a molar basis, based on previous observations that porcine proinsulin has approximately 10% the potency of insulin. Proinsulin infusion rates of 2.75, 7.5, 22.5, and 45 micrograms/m2/min were compared with insulin infusion rates of 0.63, 1.67, 5, and 10 micrograms/m2/min. Primed, continuous infusions of insulin yielded steady-state levels within 25 min, whereas proinsulin levels did not reach a steady state for 120-180 min. The metabolic clearance rate of insulin was 11-12 ml/kg/min at the lower infusion rates but fell to 8.4 ml/kg/min at the highest infusion rate. The metabolic clearance rate of proinsulin was 3.0-3.5 ml/kg/min at all infusion rates. Dose-response analysis demonstrated that proinsulin-mediated glucose disposal was approximately 8% that of insulin. In contrast, proinsulin-mediated suppression of hepatic glucose output was approximately 12% that seen with insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Conformational stress and anastomotic hyperplasia.

Late failure of synthetic vascular grafts to small-diameter arteries (less than or equal to 4 mm) is commonly due to anastomotic hyperplasia. Theoretic analysis suggests that conformational changes at the anastomosis lead to high localized arterial wall stress caused by increases in radius of curvature of the artery (law of Laplace: tension = pressure X radius). Nine 3 kg rabbits had a plastic insert implanted into the infrarenal aorta. The insert was designed to recreate the conformational changes caused by the anastomosis of a synthetic graft to a small-diameter artery, without significantly altering blood flow. The increase in arterial wall tension created by the insert was calculated to be 80% to 100% over baseline values. Aortography, real-time ultrasound, and computed tomography (CT) scanning were done to confirm the absence of luminal thrombus formation or migration of the insert. Ultrasound and CT scans also confirmed the desired conformational changes in the aorta at the site of the insert. Aortas, with the inserts in place, were removed from 3 days to 6 months after implantation. Implantation times of 1 to 6 months resulted in a hyperplastic subintimal lesion characterized by fibrous tissue deposition, spindle cells (which may have been fibroblasts), and/or smooth muscle cells covered by endothelium. In contrast, two rabbits that had the insert placed and then removed at 1 minute and were allowed to survive for 37 and 72 days, respectively, demonstrated complete healing of the aorta without anastomotic hyperplasia. The arterial wall conformational changes induced in this experiment led to the formation of a lesion consistent with anastomotic hyperplasia. An increase in wall tension may have been the stimulus for this response. Prevention of anastomotic hyperplasia may require a means of uniting a graft to an artery without increasing wall tension.

Animals↗
PubMed1984

[Intestinal occlusion and enterocolitis caused by Gelopectose].

A case of intestinal obstruction and enterocolitis, probably as a consequence of inappropriate use of thickened feedings, is reported. Products which thicken feedings take an important part in the treatment of gastro-oesophageal reflux in infants. In order to thicken feedings, pectin and silicium have been added to milk. However, they may lead to an obstructive medication bezoar. Thus, it is necessary to limit their use to 3-5% of feeding and to clearly explain their potential hazards to the family.

Enterocolitis↗
PubMed1983

[Measurement of insulin sensitivity using the somatostatin-insulin-glucose test. Importance of the determination of plasma free fatty acids and insulin clearance].

Insulin sensitivity was determined in normal subjects and in subjects with possible insulin-resistance by simultaneous infusion of somatostatin, insulin and glucose. C peptide, growth hormone and glucagon were decreased by somatostatin in all subjects. Steady-state blood glucose was 2.84 mM (mean) in normal subjects and between 11 and 15 mM in the other subjects (p less than 0.01), indicating severe insulin resistance. Steady state plasma insulin was 50 mU/l (mean) in control subjects, but was markedly lower in one of the subjects with insulin-resistance and higher in the other two subjects, suggesting abnormalities in insulin clearance in these subjects. An index of insulin sensitivity taking into account these variable insulin levels was decreased in the insulin-resistant subjects (21 to 61, vs 117 to 251; p less than 0.01). Insulin-resistant subjects had increased basal levels of plasma free fatty acids (p less than 0.01) which failed to decrease during the test as in control subjects, suggesting abnormal metabolic regulation. In contrast, blood ketone bodies were normal in the basal state and decreased similarly in all subjects during the test, suggesting that hepatic ketogenesis does not resist to insulin.

Adult↗
PubMed1983

Solubilization of the UDP-glucose:1,4-beta-D-glucan 4-beta-D-glucosyltransferase (cellulose synthase) from Acetobacter xylinum. A comparison of regulatory properties with those of the membrane-bound form of the enzyme.

A procedure has been developed for the effective solubilization of UDP-glucose:1,4-beta-D-glucan 4-beta-D-glucosyltransferase (cellulose synthase) by treatment of membranes from the bacterium Acetobacter xylinum with digitonin. Low concentrations of digitonin (0.1%, w/v) cause stimulation of the enzyme activity in membranes; treatment with higher concentrations of digitonin (1-10%) results in solubilization of up to 70% of the digitonin-stimulated activity. The digitonin-solubilized enzyme displays regulatory properties quite similar to those of the membrane-bound form of the enzyme, showing specific activation by GTP. GTP activation requires the presence of a protein factor which can be separated from the enzyme by washing the membranes prior to enzyme solubilization. Association of this protein factor with the membrane-bound enzyme is promoted by polyethylene glycol or by Ca2+; however, these compounds are ineffective in enhancing enzyme-factor association for the enzyme in the solubilized state. The observation that Ca2+ promotes enzyme-factor association in the membranes suggests that this cation, in addition to GTP, may play a role in the regulation of cellulose synthesis in vivo in A. xylinum.

Arabidopsis Proteins↗
PubMed1983

Calcium-dependent 4-aminopyridine stimulation of protein phosphorylation in squid optic lobe synaptosomes.

When intact synaptosomes were incubated with [gamma-32P]ATP, maximal protein phosphorylation was attained 2 min after the start of incubation. Protein phosphorylation under basal conditions was dependent on external Ca2+, and the dominant peak of phosphorylation was a 50-kd protein. Incubation of intact synaptosomes in the presence of 3-6 mM 4-aminopyridine (4-AP) caused a markedly enhanced phosphorylation of high molecular weight proteins of 90, 100, 130, and 180 kd, with no increase in the 50 or 38 kd proteins. This effect of 4-AP was dependent on external calcium ions in the incubation medium. The 4-AP effect on the high molecular weight proteins was also found in synaptosomal plasma membranes isolated from the synaptosomes. Tetraethylammonium (TEA) ions did not produce this enhancement of phosphorylation.

4-Aminopyridine↗
PubMed1983

Immunoregulatory cell subsets in Goodpasture's syndrome: evidence for selective T suppressor-cell depletion during active autoimmune disease.

In a patient with documented untreated Goodpasture's syndrome, serial determination of T-cell subsets using monoclonal antibodies and flow cytometry revealed a persistent but variable deficiency of T-suppressor cells during the period of active disease. As the percentage of OKT8+ cells (suppressor/cytotoxic T cells) returned to normal levels, anti-basement membrane autoantibody production decreased and finally disappeared. Possible pathogenetic implications of immunoregulatory cell imbalance specifically in reference to Goodpasture's syndrome are discussed.

Adult↗