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Biomedical subjects

S Braun

Publications and source records attributed to S Braun.

At least 271 records · Page 15Linked to original sources

A tyrosine-specific protein kinase from Ehrlich ascites tumor cells.

A protein tyrosine kinase that phosphorylates both alpha and beta subunits of inactivated (Na+,K+)-ATPase from dog kidney was purified about 500-fold from Ehrlich ascites tumor cell membranes. The enzyme required divalent cations Mn2+, Mg2+, or Fe2+ but was inhibited by Cu2+ or Zn2+. The purified enzyme phosphorylated the beta subunit about five times faster than the alpha subunit of the (Na+,K+)-ATPase. The random polymer poly(Glu80Tyr20) was an excellent substrate while casein was only marginally phosphorylated. In contrast, the purified transforming gene product of Rous sarcoma virus phosphorylated all three substrates and the (Na+,K+)-ATPase was preferentially phosphorylated on the alpha subunit. The transforming gene product of Fujinami sarcoma visue and EGF receptor kinase from A431 cells phosphorylated (Na+,K+)-ATPase poorly whereas casein was an excellent substrate. The molecular weight of the partially purified protein tyrosine kinase from Ehrlich ascites tumor cells determined by gel filtration was about 60,000. One of two major phosphorylated phosphopeptides resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis had an Mr of 60 kDa, thus suggesting that it might be the autophosphorylated protein tyrosine kinase. A phosphatase that hydrolyzes phosphorylated histones or poly(Glu80Tyr20) was partially purified from the same membrane.

Animals↗

Reversion of the transformed phenotype of B16 mouse melanoma: involvement of an 83 kd cell surface glycoprotein in specific growth inhibition.

Treating B16 mouse melanoma cells with monoclonal antibody NORM-2 reduces cell growth in tissue culture, agar, and syngeneic mice. We show that the NORM-2 antibody recognizes an integral 83 kd glycoprotein that is mobile in the plane of the plasma membrane of B16 melanoma cells. Expression of the glycoprotein is reduced under conditions that inhibit B16 growth, such as low serum, high cell density, and addition of transforming growth factor-beta. The glycoprotein reappears during S phase, when growth-arrested cells are restimulated. The NORM-2 antigen appears to be involved in growth regulation of B16 melanoma cells both in vitro and in vivo.

Animals↗

Interleukin 1 inhibitory activity secreted by a human myelomonocytic cell line (M20).

Culture supernatants from a myelomonocytic cell line (M20) were found to inhibit interleukin 1 (IL 1) activity in vitro. The factor, isolated from these supernatants, inhibited augmentation of phytohemagglutinin response of mouse thymus cells induced by IL 1 derived from several established cell lines. Various IL 1-dependent activities such as lymphocyte and fibroblast proliferation in vitro were also inhibited by the factor. The factor did not inhibit IL 2-induced or other proliferative responses not related to IL 1. Preliminary biochemical characterization of the factor indicated that the activity resides in a protein with a molecular mass of 52 kDa.

Cell Division↗

Partial purification and characterization of protein tyrosine kinases from normal tissues.

Three membranous protein tyrosine kinases (PTKs) have been partially purified from human placenta and pig brain. The two placental enzymes (PTK-1 and -2) are distinct with respect to solubility in detergents, molecular weight, and enzymatic properties. The brain protein tyrosine kinase resembles placental PTK-1 with respect to molecular weight and some kinetic properties. However, stimulation of brain PTK is greater with Mn2+ than with Mg2+ whereas placental PTK-1 gives higher rates with Mg2+ than with Mn2+. All three enzymes are inhibited about 50% by 0.1 M NaCl. A monoclonal antibody raised in vitro against the brain enzyme inhibits brain PTK as well as placental PTK-2, but has no effect against PTK-1 or pp60src. It thus appears that these three enzymes are distinct entities that differ from each other both kinetically and immunologically. With synthetic tyrosine-glutamic acid polymers as a substrate, protein tyrosine kinase activity can be detected in crude extracts of membranes.

Animals↗

Effects of a kappa-opioid agonist on adrenocorticotropic and diuretic function in man.

Although kappa-opiate receptors represent an important fraction of the total opiate receptor capacity in human brain their endocrine function is unknown. We determined the effects of a kappa-opiate receptor agonist on the secretion of vasopressin, ACTH and cortisol and on diuresis. The racemic benzomorphan kappa agonist MR 2033 or its opiate active (-)-isomer, MR 2034, inhibited the release of cortisol and ACTH in 12 trials in a naloxone reversible manner; plasma levels of vasopressin were not altered. The (+)-isomer, MR 2035, did not affect the secretion of cortisol or ACTH. Surprisingly, in five other subjects large increases were observed in vasopressin, ACTH and cortisol following the kappa-agonist, which were probably elicited indirectly by aversive effects of the opioid. The subjects in whom vasopressin release was not altered by MR 2033 and MR 2034 displayed large decreases in urine osmolality which were not antagonized by naloxone. The opiate inactive (+)-isomer, MR 2035, caused no diuretic response. Subjects in whom vasopressin release was stimulated did not show decreases in urine osmolality indicating that vasopressin is capable of antagonizing the diuretic action of the kappa-agonist. Our data show that a kappa-agonist inhibits secretion of cortisol and ACTH by acting at stereospecific opiate receptors and elicits diuresis by acting at stereospecific, but naloxone-insensitive non-classical opioid receptors. These data support the concept that different types of kappa-receptors can be distinguished in man.

Adrenocorticotropic Hormone↗

Antiarrhythmic and haemodynamic effects of tiapamil, a new calcium antagonist, during coronary artery occlusion and reperfusion in dogs.

The antiarrhythmic and haemodynamic effects of tiapamil, a new calcium antagonist, were studied in 28 anaesthetised open chest dogs. Tiapamil (2 mg X kg-1 intravenously over 5 min) was infused 15 min before a 20 min ligature of the left anterior descending coronary artery in 11 dogs. In 17 dogs physiological solution was given instead of tiapamil. In this control group, ventricular fibrillation developed during coronary occlusion in 14 (82%) dogs and after coronary reperfusion in seven of 9 (77%) dogs, which reached this stage. In contrast, in the dogs pretreated with tiapamil, ventricular fibrillation did not develop during coronary occlusion in any of the 11 dogs and did develop after coronary reperfusion in only one (9%). In addition, tiapamil appreciably decreased heart rate and blood pressure and increased cardiac output and stroke volume. These antiarrhythmic and haemodynamic effects of tiapamil suggest that this drug would be useful in the management of patients with coronary artery disease.

Animals↗

Factors contributing to forest decline in northwestern Switzerland.

Possible causes of decline of 37 beech (Fagus sylvatica L.) forests in northwestern Switzerland were investigated. The trees were assessed for symptoms of damage or disease including loss of leaves, chlorosis and dead shoots. In addition, nutrients and pollutants were analyzed in soil, leaves, stemflow and rainwater. Air pollutants were monitored at several sites. The results indicate that a variety of factors may have contributed to forest decline.

Journal Article↗

Anterior pituitary hormone responses to a kappa-opioid agonist in man.

The present study was designed to investigate pituitary hormone responses to a kappa-opiate receptor agonist in man. Normal men were given the racemic benzomorphan kappa-agonist MR 2033 or its levorotatory isomer MR 2034 iv. Plasma levels of PRL and GH markedly increased after injection of 3.5 micrograms/kg MR 2033 or 1.9 or 3.8 micrograms/kg MR 2034. These effects of MR 2033 were blocked by the opiate antagonist naloxone (10 mg), thereby demonstrating their mediation by opiate receptors. The kappa-agonist did not change plasma levels of LH and FSH. The secretion of TSH was significantly suppressed by MR 2033 and MR 2034, but this action was not antagonized by pretreatment with naloxone. The suppression of plasma TSH was, however, stereospecific since the (+)-isomer, MR 2035, did not affect TSH secretion. These data indicate that kappa-opiate receptors are located on neuronal pathways regulating GH, TSH, and PRL secretion. The pattern of pituitary responses elicited by the kappa-agonist differs from that of mu-opioid agonists, indicating differential endocrine functions for the endogenous agonists.

Adult↗

Detection of different interleukin-1 activities in human monocytes and monocytic cell lines.

Culture supernatants from normal human monocytes, monocyte hybrid cell lines, and myelomonoblastic cell lines were tested for human interleukin-1 (IL-1) activity. In the present study, we report the detection of IL-1 secreted by several cell lines of monocyte origin and compare their biological and biochemical characteristics. IL-1 activity was tested by the regular assay of phytohemagglutinin (PHA) response of mouse thymus cells. IL-1 was found to be constitutively secreted by U937 and the M20 cell lines, as well as by three of the monocyte hybrid cell lines. The activity was always augmented following dialysis and did not require the presence of serum for its secretion. We compared the IL-1 activity of the myelomonoblastic M20 and hybrid 1C4 cell lines to that of normal monocytes. We found differences in the kinetics of IL-1 secretion, the pattern of activity following dilution of concentrated supernatants, and augmentation of activity by various inducers. The differences described may be explained by concomitant secretion of IL-1 inhibitory factors, as well as the secretion of activities other than IL-1. Preliminary biochemical analysis showed that all three cell sources tested shared some species of molecules characterized by gel filtration and ion-exchange chromatography. However, some species of molecules expressing IL-1 activity were unique to the cell lines and were not found in normal monocytes.

Animals↗

Haemodynamic effects of Ro 13-6438, a new inotropic agent with vasodilating properties.

The chemical class 1,5 dihydroimidazo (2,1-6) guinazolin-2(3H)ones has been shown to have positive inotropic activity, some of its members displaying a favourable ratio between positive inotropic and chronotropic activity. This study was designed to determine the cardiovascular properties of Ro 13-6483, a non-glycoside, non-catechol positive inotropic agent, in anaesthetized, open chest mongrel dogs. Ro 13-6483 (1 mg/kg) was administered intravenously over a 5-min period to 6 dogs. Haemodynamic changes were measured continuously over a period of 45 min. Ro 13-6438 increased stroke volume by 61.9% (p less than 0.001) and cardiac output by 53.3% (p less than 0.001). Systolic and diastolic blood pressure decreased significantly (p less than 0.01). Heart rate did not change. The lowering of the blood pressure, without a significant increase in heart rate, observed after Ro 13-6483 administration might prove to be of value in patients with congestive heart failure, since Ro 13-6483 would reduce afterload and improve the competency of the heart, in addition to the positive inotropic effects.

Animals↗

[Angiotensin converting enzyme in the adult respiratory distress syndrome].

Angiotensin-converting enzyme (ACE) is present in high concentration in pinocytotic vesicles of the inner walls of the capillary endothelial cells of the lungs. Since a lesion of these endothelial cells is considered to be a major pathogenetic factor in adult respiratory distress syndrome (ARDS), the question arises whether serum ACE could be used as a marker enzyme in the course of ARDS to assess the syndrome's development and prognosis. The authors examined 28 patients with ARDS, 14 of whom survived acute respiratory failure. The serum ACE was determined every 48 hours. In addition, daily determination was carried out of AaDO2, pulmonary shunt perfusion (Qs/Qt) and thoraco-pulmonary compliance. In 9 of the surviving ARDS patients control serum ACE levels and lung function tests were performed half a year after recovery. 60 healthy volunteers served as controls. Definitely reduced serum ACE levels were found both in the surviving (17.1 +/- 6.9 U/ml) and dead (17.6 +/- 8.7 U/ml) ARDS patients. However, since the values for both groups are practically identical it can be assumed that determining the ACE level alone is probably not of prognostic value in acute respiratory failure. Patients who have survived ARDS show a significantly positive correlation between serum ACE and AaDO2, whereas in the patients who died a significantly negative correlation between serum ACE, AaDO2 and Qs/Qt was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Clinical and hemodynamic effects of combined propranolol and nifedipine therapy versus propranolol alone in patients with angina pectoris.

To determine the comparative effectiveness and hemodynamic effects of long-term oral treatment with propranolol alone and combined with nifedipine in patients with stable angina pectoris, 20 patients with coronary disease were studied by equilibrium radionuclide ventriculography. Measurements were performed at rest and during supine bicycle exercise before treatment, after 4 weeks on propranolol, 1 hour after institution of combined propranolol and nifedipine treatment, and after 4 weeks on the combined treatment. The reduction in exercise rate-pressure product induced by the combination (17.2 +/- 2.6 X 10(3)) was significantly greater (p less than 0.001) than that attained by propranolol alone (19.3 +/- 2.8 X 10(3)). In patients at rest, neither propranolol nor the combined therapy altered global left ventricular (LV) ejection fraction (EF). Without drugs and on propranolol, exercise EF decreased significantly. On the combined therapy there was a significant improvement in exercise EF compared both with rest values (p less than 0.01) and with exercise EF on propranolol (p less than 0.001). Exercise tolerance, expressed as total work load, significantly increased on propranolol and further increased on combined therapy. Thus the combined propranolol/nifedipine therapy in patients with stable angina proved to be hemodynamically superior to therapy with propranolol alone and safe even in patients with moderately depressed LV function.

Administration, Oral↗