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Biomedical subjects

G Baumann

Publications and source records attributed to G Baumann.

At least 325 records · Page 18Linked to original sources
PubMed1984

Apparent superiority of H2-receptor stimulation and simultaneous beta-blockade over conventional treatment with beta-sympathomimetic drugs in post-acute myocardial infarction: cardiac effects of impromidine--a new specific H2-receptor agonist-in the surviving catecholamine-insensitive myocardium.

Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to beta-adrenergic and H2-histaminergic stimulation by isoproterenol and impromidine tested in the isolated perfused heart preparation. Adenylate cyclase activity as well as binding characteristics of [3H]-dihydroalprenolol ([3H]-DHA), [3H]-methyl-tiotidine ([3H]-TIOT) and [3H]-quinuclidinyl benzilate ([3H]-QNB) to cardiac beta 1-, H2- and cholinergic muscarinic receptors were determined in sarcolemmal membrane preparations of the right ventricle of the same hearts. In addition, an attempt was made to elucidate the therapeutic value of post-AMI treatment with impromidine in the presence and absence of beta-blockade, in contrast to administration of prenalterol and the conventional therapy with beta-sympathomimetic drugs, e.g. dobutamine. Three days post-AMI the dose-response curve for isoproterenol of right ventricular dP/dtmax was significantly depressed, while the inotropic effect of impromidine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 80% whereas impromidine and NaF stimulation rates were unaltered. Receptor-binding studies indicated a 90% loss and 10-times lowered affinity (KD) of the remaining beta-receptors while specific [3H]-TIOT- and [3H]-QNB-binding was unchanged. Administration of dobutamine increased mortality rates and extension of infarct size, led to a further decrease in contractile response to isoproterenol, induced complete insensitivity of adenylate cyclase to isoproterenol stimulation and caused pronounced additional reduction of number and affinity of [3H]-DHA-binding sites. In contrast, all above alterations were prevented by treatment with either prenalterol or combined administration of impromidine plus metoprolol. It is concluded, that these alterations in the non-ischemic, uninvolved myocardium post-AMI are the result of catecholamine-induced specific damage of sarcolemmal beta-receptors. Furthermore, treatment with H2-agonists in combination with beta-blocking agents may have beneficial effects, whereas conventional therapy with beta-sympathomimetic drugs tends to worsen the already depressed function of the beta-adrenergic stimulation mechanism.

Adenylyl Cyclases↗
PubMed1984

Enhanced efficacy of U-500 insulin in the treatment of insulin resistance caused by target tissue insensitivity.

This report describes a 55-year-old diabetic patient with severe insulin resistance due to obesity and hepatic cirrhosis. Anti-insulin antibodies were responsible for only a minor part of the insulin resistance. Insulin resistance was mediated primarily at the target tissue level by a combination of insulin receptor deficiency and a postreceptor defect. When the patient was treated with U-500 regular pork insulin subcutaneously, her insulin requirement was only one third to one half of that during U-100 NPH or regular insulin treatment. The reasons for the greater efficacy of U-500 insulin are unknown. U-500 insulin may have a place in the optimization of therapy for patients with insulin resistance of nonimmunologic origin.

Diabetes Mellitus↗
PubMed1984

Kinetics of cell age-dependent decline of insulin receptors in human red cells.

Insulin receptors are present in human erythrocytes and correlate negatively with cellular age. Little is known about the function of these receptors, about the precise kinetics of their decline during cell aging or about their fate after disappearance from the cells. To elucidate some of these questions, we have prepared red blood cell populations of widely varying cellular ages (ranging from the erythroblast stage to senescent mature erythrocytes) by isopycnic centrifugation on isosmolar density gradients. In addition, young red cells were cultured for 4 days in vitro to permit observation of short-term changes. In mature erythrocytes, insulin receptors decreased as an exponential function of cell age with an estimated half time of 40 days. A more rapid decline of insulin receptors occurred coincident with reticulocyte maturation. Loss of receptors from cultured cells was accompanied by appearance of a soluble insulin receptor in the medium. The effect of insulin on glucose utilization in erythroblast and reticulocyte preparations was negligible, as assessed by CO2 and lactate production. We conclude that 1) insulin receptors are progressively lost from the red blood cell after the erythroblast stage; 2) receptor loss is particularly rapid during reticulocyte maturation; 3) shedding of receptors into the extracellular environment is one reason for their depletion from cells; and 4) in basophilic erythroblasts and reticulocytes, insulin exhibits little metabolic action despite the relatively high receptor complement present in these cells.

Blood Glucose↗
PubMed1984

Insulin receptors in acute infection: a study of factors conferring insulin resistance.

Acute infections are accompanied by tissue insulin resistance, as manifested by worsening of metabolic control in diabetic patients and decreased glucose tolerance in non-diabetic subjects. To clarify the potential role of altered insulin receptor status in this phenomenon, we studied [125I]insulin binding to monocytes in 7 otherwise healthy subjects during acute bacterial and viral infections of moderate severity. The values were compared to those obtained after convalescence (five patients) and those of 24 normal subjects. Insulin binding during infection, at a time when insulin resistance was demonstrable, was indistinguishable from convalescent or normal values. Plasma glucose and insulin levels, the insulin to glucose ratio, as well as plasma GH, cortisol, and FFA were significantly elevated during infection, while plasma glucagon, epinephrine, and norepinephrine levels were normal. We conclude that insofar as monocyte receptors are representative of other tissues, insulin resistance in infection is mediated at the postreceptor level.

Adult↗
PubMed1984

Plasma "big" and "big-big" growth hormone (GH) in man: an oligomeric series composed of structurally diverse GH monomers.

Human GH (hGH) immunoreactivity in plasma can be separated into three species of different molecular size by gel filtration (little, big, and big-big hGH). In contrast to pituitary high mol wt GH forms, the molecular nature of the big hGH forms in blood is not known. Therefore, we purified these hGH size isomers from the plasma of L-dopa-stimulated normal subjects and acromegalic patients. Plasma was chromatographed on Sephadex G-100, and fractions containing big-big, big, and little hGH were generated. hGH was extracted and concentrated from these fractions by immunoadsorbent chromatography and analyzed by polyacrylamide gel electrophoresis (PAGE), sodium dodecyl sulfate-PAGE, and isoelectric focusing. The resulting gel profiles indicated that the majority (70%) of big and big-big hGH was converted to little hGH during extraction and storage. The remainder migrated as distinct species with mol wt of approximately 45, 62, 80, and 110 K in sodium dodecyl sulfate-PAGE. These forms could be converted almost completely to little hGH by sulfhydryl reduction. Little hGH (both native and converted from big forms) was composed of several monomeric hGH species, namely the 22 K form (principal), the 20 K variant, and at least one acidic form. All hGH size isomers contained the same monomeric building blocks, although in somewhat different proportions. Big hGH, e.g. was particularly rich in 20K. No abnormal or previously unrecognized hGH forms were identified as components of big or big-big hGH. Binding of hGH to plasma proteins could not be demonstrated. We conclude that 1) plasma big and big-big hGH represent an oligomeric series composed of 22K (major), 20K, and one or more acidic hGH monomers, 2) the majority of these oligomers are noncovalently associated, with a smaller fraction consisting of monomers linked by disulfide bridges.

Chromatography↗
PubMed1984

Circulating growth hormone forms after stimulation of pituitary secretion with growth hormone-releasing factor in man.

Human GH (hGH) in the circulation of acromegalic patients and pharmacologically stimulated normal subjects consists of several monomeric and oligomeric molecular forms. However, little is known about the nature of plasma hGH under physiological conditions. We examined the molecular composition of plasma hGH secreted in response to synthetic human pancreatic tumor GRF-(1-40) (hpGRF-40), a peptide closely resembling or identical to hypothalamic GRF. The peptide (10 micrograms/kg) was injected iv into six normal men, and blood was obtained 30 min later. Plasma hGH was characterized by gel filtration and by polyacrylamide gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and isoelectric focusing after extraction from plasma by immunoadsorbent chromatography. At least 53% of hGH eluted as little (monomeric) hGH, 27% as big (dimeric) hGH, and 20% or less as big-big (oligomeric and spurious) hGH during gel filtration. Among the monomeric forms, the 22,000-dalton form was predominant (83%), with smaller quantities of the 20,000-dalton variant (11%), and one or more unidentified acidic forms (N alpha-acetylated, deamidated, or cleaved hGH) (6%) also present. The molecular composition of plasma hGH secreted in response to hpGRF-40 is similar to that released after pharmacological stimuli or that circulating in acromegaly.

Adult↗
PubMed1983

The orientation of insulin receptors in the red cell membrane.

High-affinity binding of insulin to receptors in human erythrocyte membranes occurred at the external surface, but not at the cytoplasmic surface of the plasma membrane, as assessed by insulin binding to right-side-out and inside-out membrane vesicles. Even after prolonged (3 h) incubation at 22 degrees C, binding at the cytoplasmic membrane aspect remained negligible. The data indicate that the insulin receptor displays its hormone-binding site exclusively toward the extracellular space and that transmembrane mobility ("flip-flo") of the receptor from one to the other membrane leaflet is severely restricted.

Acetylcholinesterase↗
PubMed1983

Urinary growth hormone in man: evidence for multiple molecular forms.

Human GH (hGH) consists of several molecular forms. Monomeric forms present in pituitary extracts include the single chain, 22,000 mol wt form (22K; hGH-B); a 20,000 mol wt, single chain variant (20K); three proteolytically cleaved, two-chain forms (hGH-C, -D, and -E), acetylated, deaminated, and slow-migrating forms. It is not known which of these forms are secreted in vivo or whether peripheral organs contribute to the interconversion between some of these hGH forms. To answer these questions, we studied the molecular forms of hGH excreted in urine from normal volunteers and from an acromegalic patient, as urinary hGH presumably reflects integrated plasma hGH. hGH was extracted from urine by hollow fiber diafiltration and concentration, followed by immunoadsorbent chromatography. The extracted hGH was examined by polyacrylamide gel electrophoresis under native as well as denaturing and reducing conditions and by isoelectric focusing. The predominant form of hGH in both normal urine and urine from the acromegalic patient was 22K, with small quantities (approximately 10%) of 20K and an unidentified acidic form also present. Cleaved forms with enhanced bioactivity (hGH-D and -E) and big hGH forms were not detectable. We conclude that 1) the pattern of urinary hGH suggests that spontaneously secreted and circulating hGH is composed of at least three hGH forms, with 22K predominating; 2) the pattern of urinary hGH is similar to that of plasma hGH after L-dopa stimulation; 3) hGH excreted in acromegaly is indistinguishable from hGH excreted by normal subjects; 4) only a minute fraction (less than 0.01%) of the hGH secreted reaches the final urine; and 5) renal interconversion among hGH forms does not appear quantitatively important.

Acromegaly↗
PubMed1983

The molecular nature of circulating growth hormone in normal and acromegalic man: evidence for a principal and minor monomeric forms.

Human GH (hGH) extracted from pituitary glands consists of several molecular forms. Monomeric pituitary forms include the single chain 22,000-dalton polypeptide (22K; hGH-B), a 20,000-dalton variant with a 15-amino acid deletion (20K), 3 proteolytically cleaved 2-chain forms (hGH-C, -D, and -E), 2 deamidated forms, an acetylated form (fast hGH), and other, only partially characterized forms. It is not known which of these forms is secreted, nor what the precise nature of circulating hGH is. To answer these questions, we have extracted hGH from human plasma obtained by plasmapheresis from normal volunteers after L-dopa stimulation of hGH secretion and from acromegalic patients. We extracted and concentrated hGH by immunoadsorbent chromatography and examined its chemical nature by polyacrylamide gel electrophoresis under native and denaturing (sodium dodecyl sulfate and urea), nonreducing and reducing (dithiothreitol) conditions as well as by isoelectric focusing. In all cases, the predominant form of hGH present in plasma was 22K, which accounted for approximately 85% of all immunoreactive hGH. In addition, we found evidence for the presence of 20K as a minor form (approximately 7% of all hGH) and of one or more acidic forms (N-acetylated, deamidated, or cleaved hGH; 5-10% of all hGH). Exact identification of the acidic form(s) was not possible. However, the highly bioactive cleaved forms hGH-D and -E were judged to be undetectable (less than 5% of all hGH). We conclude that 1) several monomeric molecular forms of hGH circulate in normal and acromegalic man; 2) the pattern of circulating hGH forms reflects in part their relative prevalence in the pituitary gland; 3) proteolytically cleaved 2-chain hGH forms with enhanced bioactivity are not detectable in blood; and 4) monomeric hGH circulating in acromegaly is qualitatively indistinguishable from normal hGH.

Acromegaly↗
PubMed1983

Circadian variation of basal plasma growth hormone in man.

Human GH (hGH) circulating during periods of basal pituitary secretion is frequently undetectable in human plasma by RIA. Such basal periods predominate throughout most of the day. Knowledge of the concentration of basal hGH is important, since hGH plays a role in the homeostasis of several metabolic fuels and ions. We have used an immunoadsorbent technique to extract and concentrate hGH from large plasma samples before RIA in order to precisely measure basal hGH levels [immunoextracted RIA (IERIA)]. Twenty milliliters of blood were drawn from five normal volunteers every 2 h over a 24-h period. The obtained plasma (10-13 ml) was passed over an anti-hGH antibody Sepharose column. The column-bound hGH was eluted and measured by RIA. Recovery of hGH in the plasma extracts was measured using [131I]hGH as an internal standard. Recovery averaged 54 +/- 12% (mean +/- SD). Theoretically, the extraction procedure expanded the useful range of the RIA about 50-fold. In practice, the detection limit was 40 pg/ml plasma. Basal hGH (defined as less than 1 ng/ml by conventional RIA) was found to range from less than 40 to 746 pg/ml by IERIA. Above 2 ng/ml, conventional RIA and IERIA yielded comparable results (r = 0.92; P less than 0.001), but below 2 ng/ml, the two assays did not correlate (r = 0.01; P greater than 0.5). In general, conventional RIA overestimated plasma hGH in that range. As a result, the ratio between nocturnal and daytime hGH secretion, as assessed by IERIA, is higher than previously appreciated. We conclude that basal plasma hGH is highly variable below 1 ng/ml, and may on occasion be as low as less than 40 pg/ml. The episodic nature of hGH release appears to persist in the basal state. The conventional definition for basal hGH (less than 5 ng/ml) should probably be revised downward to less than 0.8 ng/ml.

Adult↗
PubMed1983

Estrogens and the hypothalamo-pituitary-adrenal axis in man: evidence for normal feedback regulation by corticosteroids.

Estrogen treatment and pregnancy are associated with higher than normal plasma free (nonprotein-bound) cortisol levels. In spite of this, clinical manifestations of steroid excess are not seen in these conditions. To explain this seeming discrepancy, it has been postulated that estrogens may induce tissue resistance to the actions of cortisol, and that one aspect of this resistance may be a higher set-point for ACTH suppression by corticosteroids. This possibility was studied in seven normal women. Plasma total and free cortisol levels as well as urinary cortisol excretion were measured during a control period and during treatment with ethinyl estradiol (100 micrograms/day). During both periods, graded doses of dexamethasone (0.2-mg increments; 0-1.4 mg/day) were administered. Estrogen treatment resulted in elevated plasma total and free cortisol levels, but urinary cortisol excretion was not affected. Dexamethasone administration resulted in a dose-dependent reduction of plasma total and free cortisol as well as urinary cortisol. The dose-response curve for suppression by dexamethasone of urinary cortisol during estrogen treatment was indistinguishable from that during the control period. The dose-response curve for plasma free cortisol suppression suggested that during estrogen treatment, slightly more dexamethasone was required to suppress free cortisol. However, this effect was small. In view of the overall data, we conclude that 1) estrogen does not increase integrated free cortisol prevailing in vivo; 2) estrogen does not significantly alter the hypothalamic or pituitary set-point for ACTH suppression by corticosteroid; 3) the elevation of plasma free cortisol is relatively minor and possibly an in vitro phenomenon; and 4) the present findings are compatible with the absence of clinical hypercorticism in hyperestrogenized states.

Adrenal Cortex Hormones↗
PubMed1982

Deleterious effects of cimetidine in the presence of histamine on coronary circulation. Possible clinical implications in anaphylactic states in individuals with coronary heart disease.

The present study characterizes effects of histamine in the presence of the H2-antagonist cimetidine on the coronary circulation of the isolated perfused spontaneously beating guinea pig heart. Infusion of histamine (2 x 10(-8) mol/1-5 x 10(-6) mol/l) induced a dose-dependent coronary dilation, comparable to the effect of isoproterenol and two highly-selective H2-agonistic compounds, impromidine and dimaprit. In the presence of cimetidine (5 x 10(-6) mol/l), however, coronary response to histamine was reversed in a manner that a dose-dependent coronary constriction occurred with coronary spasm and a flow rate approaching zero at histamine concentrations above 8 x 10(-7) mol/l, whereas the dilatory effect of impromidine and dimaprit was completely antagonized. In contrast, the histamine-induced constriction in the presence of cimetidine could be nearly abolished by additional infusion of the H1-antagonistic compound mepyramine (5 x 10(-5) mol/l). Is is concluded that H1- and H2-receptors are present in the coronary smooth muscle, H1-receptors mediating constriction and H2-receptors mediating coronary dilation. Speculation is provided that histamine may have hazardous effects in anaphylactic states if cimetidine is administered simultaneously, e.g., to prevent or cure peptic ulcer. Other possible clinical implications will be discussed.

Anaphylaxis↗
PubMed1982

Insulin receptors and insulin resistance in human pregnancy: evidence for a postreceptor defect in insulin action.

Pregnancy is accompanied, in its later stages, by physiological resistance to the action of insulin. We studied the potential contribution of altered insulin receptors to this phenomenon in 12 healthy pregnant women during their third trimester. For comparison, we studied the same women again several weeks postpartum. We also used a group of randomly chosen nonpregnant subjects as a control population. Women in this control group were studied during the luteal phase of the menstrual cycle. Plasma insulin and insulin to glucose ratios were significantly higher in the pregnant women. Insulin binding to peripheral blood monocytes was higher in pregnancy than postpartum in the majority of women, and as a group, the pregnant subjects showed significantly higher insulin binding than the nongravid subjects. This appeared to be due to a greater number of receptor sites per cell. We found no correlation between plasma insulin and insulin binding in pregnancy. We conclude that the insulin resistance of pregnancy is not attended by impaired binding of insulin to cellular receptors, at least in the monocyte. Our data suggest that the defect in insulin action lies at a site distal to the receptor.

Adult↗