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Biomedical subjects

J Roth

Publications and source records attributed to J Roth.

At least 775 records · Page 43Linked to original sources
PubMed1975

Cell membrane receptors for polypeptide hormones. Application to the study of disease states in mice, and men.

Recent studies have suggested that the first step in the action of polypeptide hormones and catecholamines is binding to surface membrane receptor sites. This interaction can be studied directly using radioactively labeled hormones and a variety of receptor preparations. With these radioreceptor assay technics, it has been possible to define structure-activity relationships and to assay plasma hormones. These studies have also been used to define alterations in the hormone receptors in disease that lead to peripheral resistance to hormonal action and to characterize the factors that regulate receptor concentrations.

Adrenocorticotropic Hormone↗
PubMed1975

Defect in insulin binding to receptors in obese man. Amelioration with calorie restriction.

With insulin at 0.1 ng/ml, the binding of (125I)insulin in vitro to circulating lymphocytes from 11 obese patients was less than that observed with cells from 10 thin volunteers. Furthermore, with obese cells, unlabeled insulin was less effective in competing with labeled hormone for binding, both at low and high concentrations of unlabeled insulin. These differences were not accounted for by the high concentrations of insulin in the circulation of the obese patients at the time fthe blood was drawn, or by differences in degradation of hormone, or in the characteristics of the cell population. The decrease in binding appears to be due to a lowering of the receptor concentration, but some loss of affinity has not been excluded. Institution of a calorie restricted diet (nine patients) which ameliorated the hyperinsulinemia, produced an improvement in hormone binding. Since the insulin receptors of lymphocytes in metabolic disorders seem to reflect the state of insulin receptors or target cells such as liver and fat, the lymphocytes or other leukocytes appear to be ideal for studies of impaired cell responsiveness to hormones in man.

Adult↗
PubMed1975

Insulin receptor deficiency in genetic and acquired obesity.

We have previously shown that in the insulin-resistant obese hyperglycemic mouse (ob/ob) there is a deficiency in the number of insulin receptor sites on hepatocytes, adipocytes, and thymic lymphocytes. We now find that concentration of insulin receptors on liver plasma membranes is decreased in the db/db mouse, another form of inherited obesity, and in normal mice that became obese after treatment with gold thioglucose, while thin mice, heterozygous for the ob mutation (ob/+), have normal insulin binding. With acute and chronic food restriction of the ob/ob and gold thioglucose obese mice, there is reduction in hyperinsulinemia and an associated increase in the insulin receptor concentration toward normal. In contrast, when fasting ob/ob mice were given exogenous insulin to maintain the hyperinsulinemia, insulin receptors failed to increase. Thus, in all cases, there was a consistent relationship between the degree of hyperinsulinemia and of insulin receptor loss. These findings suggest that decreased insulin binding is a characteristic feature of the insulin resistance of obesity, and that sustained hyperinsulinemia is a major factor in the control of the concentration of insulin receptors on target cells.

Adipose Tissue↗
PubMed1975

Radioreceptor assay of insulin: Comparison of plasma and pancreatic insulins and proinsulins.

Porcine proinsulin, related intermediates and plasma immunoreactive insulin components have been studied by radioreceptor assay. Using the purified rat liver membrane or cultured human lymphocyte radioreceptor assay, porcine proinsulin is %5, split proinsulin 6% (54-55 split in connecting peptide) desdipeptide proinsulin 20% (deletion of amino acids 62 and 63 of connecting peptide) and desnonapeptide proinsulin 27% (deletion of amino acids 55-63 of connecting peptide) as active as porcine insulin in both assay systems; these values closely parallel the in vitro bioactivity of these preparations. In the lymphocyte radioreceptor assay the human plasma immunoreactive insulin-like component has the same potency as porcine insulin per immunoreactive unit, whereas the plasma immunoreactive proinsulin-like component is only 15% as active. Since both plasma immunoreactive components are somewhat less reactive than would be expected from puriified human insulin and proinsulin, the data suggest that both plasma components contain immunoreactive molecules that do not react in the radioreceptor assay.

Animals↗
PubMed1975

Circulating NSILA-s in man: Preliminary studies of stimuli in vivo and of binding to plasma components.

The insulin-like peptide NSILA-s (non-suppressible insulin-like activity soluble in acid ethanol) was measured in plasma using gel filtration in acid and a new radioreceptor assay. Total plasma NSILA-s levels, which are elevated in some patients with extrapancreatic tumors and hypoglycemia, were also found to be elevated in pregnancy. Patients with hypopituitarism had subnormal concentrations of total plasma NSILA-s which rose promptly and reached a peak 1 h after intravenous hGH. In contrast ot this acute stimulus, chronic elevation of hGH resulted in an elevated level of NSILA-s in only 1 of 10 acromegalics. In normal subjects, oral glucose loading resulted in a rise in NSILA-s (mean peak equals 151% of basal) while insulin induced hypoglycemia produced a small and variable fall. Among the other conditions studied, anorexia nervosa was associated with low levels of NSILA-s. Using gel filtration we found that at physiologic pH about 93% of endogenous NSILA-s is reversibly bound to larger molecules. We show that in normal adults the insulin-like bioactivity in plasma due to free NSILA-s in the basal state is equal to that exerted by insulin itself, and that the free NSILA-s in the circulation of patients with extra-pancreatic tumors approximates the elevated level of insulin in patients with insulin-secreting pancreatic tumors.

Acromegaly↗
PubMed1975

Hyperinsulinemia and hypoinsulinemai. Insulin responses to oral carbohydrate over a wide spectrum of glucose tolerance.

Oral glucose tolerance tests using a 75 gm. carbohydrate load were performed on 396 Pima Indians. Subjects were divided into groups on the basis of two-hour plasma glucose levels and the patterns of insulin response examined. Two-hour insulin levels were highest in the group with two-hour plasma glucose levels between 140-169 mg,/100 ml. and then fell progressively until levels about 400 mg./100 ml. were reached. Half and one-hour insulin levels showed little change in the groups with two-hour glucose levels up to 170 mg,/100 ml., but at higher glucose levels these insulin levels also progressively diminished. Fasting insulin levels were relatively unchanged over the entire range of glucose inintolerance. Obesity was the most important factor influencing the fasting insulin levels. Glucose level was the major determinant of post-load insulin responses, but these were also significantly influenced by obesity. No effect of age or sex on insulin levels was demonstrated. Comparison with other published data indicated that different interpretations of insulin response in subjects with "mild diabetes" have resulted from comparisons of groups with different degrees of glucose tolerance.

Adolescent↗
PubMed1975

Rejection and repair of endothelium in major vessel transplants.

Fresh saphenous vein homografts are gaining popularity as conduits for femoral-popliteal or distal bypass grafts. Aside from major blood group compatibility, there is little clinical evidence that rejection is a significant factor in long-term patency. Some have suggested that blood vessels are weakly antigenic and others indicate that rejection does not endanger long-term patency. Transplantation and toxic damage were produced in experimental animals in order to compare healing processes. Both types of injuries produced early significant endothelial cell proliferation detected by H3-thymidine uptake. This response peaked at 5 days in transplants and ever-expanding islands of proliferating endothelium were present in aortas exposed to 20 percent sodium chloride, leading to healing in 3 to 4 months. In the transplanted vessels, total endothelial destruction occurred at 11 to 28 days, and cells of host origin determined by sex chromatin analysis gradually resurfaced those grafts that maintained patency. At 4 months only two of six carotid artery homografts were patent in unmodified dogs, and eight of nine were patent in animals given 1 mg. per kilogram of Imuran. All patent grafts were resurfaced by host cells. We conclude that rejection does play a role in long-term patency; that donor endothelium of living vascular grafts cannot maintain sufficient proliferative capacity to repair immunological damage; that small doses of Imuran significantly alter the rate of destruction leading to more orderly repair and patency; and that clinical trials utilizing one half the dose of Imuran required for kidney graft survival are likely to improve significantly the long-term patency rate of fresh arterial or venous homografts in man.

Animals↗
PubMed1975

[Investigations of chronic bronchitis and bronchial obstruction in miners].

655 ore miners were investigated for detection of a chronic bronchitis, of difficulty in breathing and bronchial obstruction. Dependent on age and period of occupational life there was observed an increase in frequency of abnormal findings. Smoking cigarettes must be considered as a important cause of development of these diseases. On the other hand the importance of occupational influences recedes on conditions that the labour hygiene norms are observed.

Adult↗
PubMed1975

[Bronchial obstruction and bronchial hyperreactivity as a cause of difficulty in breathing that depends on burden and weather].

356 male patients (non-suffering from the lungs, recidivity-bronchitis or chronic bronchitis) were interrogated about the presence of difficulty in breathing that depends on burden and weather, and these patients were investigated for detection of a bronchial obstruction and a bronchial hyperreactivity. With the increased degree of a manifest bronchial obstruction a high-significant increase in frequency of load-dyspnea was demonstrated. On the other hand a significant increase of difficulty in breathing that depends on weather can be obtained only in patients with bronchial hyperreactivity. To estimate more differentiated the difficulty in breathing about which the patients pointed out, an investigation by means of the acetylcholine test is necessary.

Acetylcholine↗
PubMed1975

[Significance of the acetylcholin-test in screening and evaluation of recurrent and chronic bronchitis (author's transl)].

156 healthy persons, 198 patients with recurrent bronchitis and 112 patients with chronic bronchitis showed different reaction to the acetylcholin test. Frequency of cough-reaction (bronchosensorial hyperreactivity) was high-significant lower in healthy persons (17,3%) than in patients with recurrent (30,8%) or chronic bronchitis (54,5%). Frequency of obstructive reaction (bronchomotorial hyperreactivity) was less but still significant different in these 3 groups (32,7%; 39,4%; 52,7%). The author proposes to pay more attention to acetylcholin-cough-test.

Acetylcholine↗
PubMed1975

[Importance of acetylcholine-test for workers under medical supervision by industrial physicians and the prophylactic examination of patients with obstructive lung-diseases (author's transl)].

2316 persons, predominantly underground miners, aged up to 64 years were investigated with the acetylcholine-test (ultrasonic aerosol device for individual inhalation "TuR", USI3, 0,2% solution, 3 min duration of inhalation) to detect bronchial hyperreactivity (decrease in the first-second-flow-test about 30% compared with the initial value 5 min. after finishing inhalation). This method permits an early diagnosis of bronchial obstruction and helps to distinguish between a stable and unstable reaction of the bronchial system. In 75 (4,4% from 1714) patients without and 57 (14% from 434) patients with manifest ventilation disorders a bronchial hyperreactivity was found. Restrictive disorders did not influence bronchial hyperreactivity. With increasing degrees of manifest bronchial obstruction a highly significant prevalence of bronchial hyperreactivity was demonstrable. Patients with a slight manifest bronchial obstruction tended significantly more frequent to intensified bronchospastic reactions. Periodical health examinations for early detection and dispensary care for persons with bronchial obstruction and obstructive respiratory diseases should be attained. The standardization of this examination is discussed, because in 60,2% there was a positive cough reaction and in 2% the inhalation had to be stopped prematurely. The one-step-method of inhalation with a acetylcholine-solution (0,1%) is proposed.

Acetylcholine↗