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G Baumann

Publications and source records attributed to G Baumann.

At least 271 records · Page 15Linked to original sources
PubMed1990

Non-random spatial distribution of intermembraneous particles in red blood cell membrane.

A combined analysis using digital image processing and quantitative evaluation of computed radial distribution of freeze fracture P face particles irradiated and nonirradiated has been carried out. Important quantitative features of the arrangement of particles can be described by computing a statistical measure, the radial distribution function g(r), commonly used to study the structure of liquids. The coordinates for calculating g(r) for each sample were measured automatically by a digital image processing system. The results for the radial distribution function were found to closely resemble g(r) for fluids, indicating the presence of shortrange order. This measure distinguishes three different patterns: i) random distribution, ii) dilute gas like and iii) a liquid like model. The mean number of first nearest neighbours surrounding each particle (coordination number) was found to be of the order of three. The RBC intramembraneous particles are heterogeneous in their behavioural pattern: two thirds random; one fifth, dilute gas; and one tenth, liquid.

Animals↗
PubMed1990

Cardiovascular effects of forskolin (HL 362) in patients with idiopathic congestive cardiomyopathy--a comparative study with dobutamine and sodium nitroprusside.

Forskolin, a diterpene derivative of the Indian plant Coleus forskhohlii, proved to be a marked positive inotropic and vasodilatory compound in animal experiments with a mechanism of action distinct from catecholamines, cardiac glycosides, and phosphodiesterase-inhibiting compounds. The cardiovascular effects of forskolin seem to be mediated by a direct stimulatory action at the catalytic unit of sarcolemmal adenylate cyclase. The aim of the present study was to clarify the cardiovascular profile of this compound in 12 patients with stage III (NYHA) congestive cardiomyopathy. The effects of forskolin were investigated by invasive techniques using the thermodilution catheter method and compared to the beta 1-receptor agonist dobutamine and the vasodilator sodium nitroprusside in an intraindividual comparison. Forskolin dose-dependently reduced cardiac pre- and afterload values, and led to a reduction in systolic, diastolic, and mean pulmonary artery pressure as well as pulmonary wedge pressure by greater than 50% concomitant with an increase in cardiac output. There was a slight increase in heart rate. Cardiac stroke volume and stroke volume index was increased by approximately 70%. The cardiovascular effects of dobutamine and nitroprusside were less pronounced; however, it seemed that a similar hemodynamic profile could be achieved by the combination of both dobutamine and sodium nitroprusside. In view of the rapid development of tolerance toward beta 1-receptor stimulation, forskolin, with its receptor-independent mechanism of action, may be advantageous for the treatment of severe heart failure, especially in patients with catecholamine-insensitive heart failure.

Adult↗
PubMed1990

Effects of platelet-activating factor on myocardial contraction and myocardial relaxation of isolated perfused guinea pig hearts.

Platelet-activating factor (PAF) is an important mediator of cardiovascular shock owing to immunologic reactions, including anaphylaxis and endotoxaemia. Previous studies have shown that PAF is a potent cardio-depressive agent causing a marked coronary constriction and a sustained impairment of myocardial contractility. In this study, we attempted to characterize further the prolonged PAF effects on coronary circulation and myocardial contractile force in isolated guinea pig hearts perfused at constant pressure (60 cm H2O) or constant flow which was adjusted to a level of 100% above basal flow. In addition, the PAF-induced changes of ventricular systolic and diastolic function were distinguished. In the hearts perfused at constant pressure, PAF induced a dose-dependent (0.57, 5.7, and 57 pmol/min) decrease of coronary flow rates, left ventricular pressure (LVP), LV contraction (peak positive dP/dt) and LV relaxation (peak negative dP/dt). The decrement of peak negative dP/dt was more pronounced than that of peak positive dP/dt. Maintenance of coronary flow rates only attenuated, but did not suppress, the PAF-induced ventricular malfunction, and it improved ventricular relaxation less than it did ventricular contraction. Pretreatment with the PAF antagonist WEB 2086 (19.7 nmol/min) almost completely abolished the effects of the highest PAF dose on coronary circulation and ventricular contractile parameters. We conclude that the cardiodepressive effects of PAF are due to coronary constriction and direct contractile events. Furthermore, PAF impairs ventricular diastolic function more than ventricular systolic function.

Animals↗
PubMed1990

Growth hormone binding proteins and various forms of growth hormone: implications for measurements.

GH measurements are complicated by numerous physiologically occurring GH forms, by the lack of availability of completely specific reagents for the various GH isoforms, and by interference of the circulating BP in some assays. The discrepancies between assay results are partly due to these factors, with monoclonal immunoassays or RRAs being more affected than polyclonal immunoassays.

Biological Assay↗
PubMed1990

Randomized double-blind cross-over study of Sinemet-controlled release (CR4 50/200) versus Sinemet 25/100 in Parkinson's disease.

Sinemet-controlled release (CR4) consisting of 50 mg carbidopa/200 mg levodopa was compared with Sinemet 25/100 in 24 Parkinson's disease (PD) patients during a 16-week double-blind cross-over study. The mean age of the patients was 66.2 years, their mean duration of PD was 9.3 years. All of the patients had response fluctuations consisting mainly of the 'wearing-off' phenomenon. Some of the patients also experienced the 'on-off' phenomenon. All patients were evaluated using the unified Parkinson disease rating scale. The following significant differences were noted on Sinemet CR4. More patients noted a decrease in dyskinesias and response fluctuations; more patients experienced a decrease in stage when 'on'; more patients were 'on' longer during the day, and more patients were globally improved. The mean number of doses per day were significantly less on Sinemet CR4 (mean 5.0, range 3-8) than on Sinemet 25/100 (mean 6.2, range 4-11 doses/day). The mean dose of levodopa in Sinemet CR4 was 1,186 +/- 458 mg and the mean dose of carbidopa was 797 +/- 115 mg. The mean dose of levodopa in Sinemet 25/100 was 873 +/- 304 mg and the mean dose of carbidopa was 218 +/- 76 mg. This study indicates that Sinemet CR4 is a useful addition for patients with response fluctuations.

Aged↗
PubMed1990

Diurnal pattern of plasma growth hormone-binding protein in man.

The identification of specific GH-binding proteins (GH-BP) in human plasma, one of which is a fragment of the GH receptor, has added new complexity to the state of GH in the circulation. A major proportion of GH circulates in complexed form, which differs in kinetics and possibly bioactivity from free GH. Little is known about the regulation of the GH-BP, their constancy or variation in plasma, or plasma factors affecting GH binding. Consequently, the temporal pattern of bound and free GH in plasma is also unknown. Knowledge about possible spontaneous variability in GH-BP levels/activity is required for physiological investigations and comparative studies among different populations. To address these issues, we measured GH-binding activity in plasma every hour over a 24-h period in six normal adults (three men and three women). A standardized GH binding assay, employing incubation of plasma with [125I]GH and separation of bound from free GH by gel filtration, was used. GH-BP activity showed no significant diurnal variation in any subject. The average GH-BP activity was similar in all subjects, although statistically significant differences were found between some subjects. No age- or sex-related differences were identified. We conclude that in normal man plasma GH-BP activity is constant throughout the day, thereby implying 1) constancy of binding protein (and possibly GH receptor) concentration, and 2) absence of significant fluctuations in potential binding inhibitors/enhancers in plasma.

Adult↗
PubMed1990

A second, lower affinity growth hormone-binding protein in human plasma.

In our previous description of the circulating GH-binding protein (GH-BP) we observed, in addition to the main GH-BP complex, a second macromolecular component designated peak I during gel filtration of [125I]GH-plasma mixtures. This component was not further characterized because of its small magnitude, seeming nonsaturability, and suspected artifactual nature. We have now characterized peak I as the complex of a low affinity BP with GH. To gain a better knowledge of the nature of peak I, whole plasma or plasma fractions containing isolated peak I-BP (ammonium sulfate precipitated or prepared by gel filtration of plasma) were incubated with monomeric [125I]GH and varying concentrations of unlabeled GH. The mixtures were then analyzed by Sephadex G-100 chromatography to separate free from protein-bound GH. Peak I-associated radioactivity was saturable at high concentrations of human GH, but not with animal GHs. Saturation/Scatchard analysis yielded an association constant of 10(5) M-1 and a maximum binding capacity of 15 mg/L plasma. Chemically cross-linked complexes of [125I]GH with isolated peak I BP were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and two-dimensional electrophoresis. These experiments yielded a mol wt of 124 kD and a pI of 7 for the cross-linked complex. This is in contradistinction to the previously reported high affinity GH-BP complex, which when cross-linked has a mol wt of 76 kD and a pI of 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗
PubMed1990

Basal plasma growth hormone levels in man: new evidence for rhythmicity of growth hormone secretion.

Circulating GH levels in man fluctuate widely due to pulsatile GH secretion by the pituitary gland. During much of the time, plasma GH is undetectable by current assays. This is punctuated by occasional secretory episodes, resulting in plasma GH peaks of varying height. The principal diurnal secretory event for GH is that associated with early slow wave sleep, but little is known about the prevailing level and dynamics of GH during the day. We used a new ultrasensitive immunoradiometric assay for GH (Boots-Celltech IRMA; limit of detection, 20 ng/L) to measure plasma GH in the previously undetectable range and to assess its diurnal pattern. Plasma GH was measured every 20 min over a 24-h period in 12 normal subjects (6 men and 6 women, aged 20-47 yr) under physiological conditions. Time series analysis of plasma GH patterns was performed by the Cluster algorithm, autocorrelation, and spectral analysis. Plasma GH, as measured by IRMA, was detectable at all time points and ranged from 40-19,695 ng/L. Dynamic fluctuations occurred within and above the previously undetectable range, with amplitudes varying over 3 orders of magnitude. Women had significantly higher overall GH levels, higher peak amplitudes, and higher valley levels/nadirs than men. GH pulses occurred with an average frequency of about 13/day in both sexes, with a dominant, but not strictly periodic, 2-h rhythmicity. We conclude that in man pulsatile GH secretion occurs throughout the day, and that it is oscillatory rather than episodic. This neurosecretory pattern has eluded recognition heretofore because of the lack of assay sensitivity. Women of reproductive age have higher pulse amplitudes and a higher baseline but equal pulse frequency compared to men. Previous estimates of integrated GH concentrations and GH production rates were too high by a factor of 2 due to overestimation of GH levels in the undetectable range.

Adult↗
PubMed1990

Plasma transport of human growth hormone in vivo.

We have previously shown that a substantial part of human GH is complexed with GH-binding proteins (BPs) when GH is incubated with plasma in vitro. The proportion of GH bound in vivo, however, is unknown and may differ because of factors that cannot be assessed in vitro, such as binding to tissue receptors, distribution of GH outside the vascular compartment, and fluctuating GH and possibly BP levels. Accordingly, we studied the plasma transport characteristics of GH in vivo in six normal men. Monomeric, natural sequence human GH (Humatrope, Eli Lilly Co.) was injected iv in a dose designed to yield physiological plasma levels. Endogenous GH was suppressed before injection with oral glucose administration. Fifteen minutes after injection, plasma was obtained and immediately analyzed by zonal and frontal analysis in gel chromatography, followed by GH measurement in the fractions by RIA. The results obtained were very similar to those derived from in vitro studies, regardless of which analytical method was used. Frontal analysis at 37 C, which most directly reflects the true bound fraction, showed that 38.8 +/- 4.7% (mean +/- SD) of GH was bound to BPs at plasma GH levels ranging from 32-59 micrograms/L, indistinguishable from in vitro results. [When allowance was made for partial BP saturation, the fraction bound at low GH levels (greater than 7 micrograms/L) was calculated as 45.5 +/- 7.5%.] There was evidence for binding to both high and low affinity BPs in the expected proportions. In contrast to complex formation between GH and BPs, no evidence was obtained for conversion of the monomeric GH to oligomeric forms. We conclude that in vitro predictions about binding of GH to BPs in human plasma are representative of in vivo conditions. Shortly after a GH pulse, almost half of plasma GH circulates in complexed form, primarily bound to the high affinity (receptor-related) BP. Aggregation of GH in plasma does not occur (at least within a 15-min period), suggesting that the pituitary is the predominant, if not sole, source of circulating GH oligomers.

Carrier Proteins↗
PubMed1990

Growth hormone-binding protein: II. Studies in pygmies and normal statured subjects.

The serum concentrations of a specific GH-binding protein, derived from the GH receptor, were assayed in sera from 62 African pygmies and 101 normal statured controls. Samples were assayed in the absence and presence of excess GH using 2 separatory procedures. Interassay variability for samples was corrected by a standard reference pool of sera from adults assayed with all unknown samples. Results were expressed as specific binding relative to this standard. The mean percent relative specific binding for GH increased with age in normal-statured controls throughout childhood and adolescence. Relative specific binding for GH was 37.0 +/- 2.0% (mean +/- SEM) in control subjects between the ages of 1-5 yr (mean age, 2.9 yr) and increased progressively to 93.0 +/- 7.0% in young adults (mean age, 23 yr). The relative specific binding of GH by serum from pygmies did not exceed 30.1 +/- 3.4% of the control adult standard at any age period (P less than 0.001), and there was no progressive age-related increase in binding. The decrease from normal binding was minimal in pygmies during childhood (29%), but the decrease from normal was 60-70% in adolescents and adults. Thus, short stature in pygmies probably results not from an absolute deficiency of GH receptors per se, as in Laron dwarfism, but from a failure of cellular GH receptors to increase in a normal manner. This is most compatible with a change in regulating expression of the GH receptor gene, rather than a structural defect in the coding sequence of the GH receptor gene.

Adolescent↗
PubMed1990

Plasma transport of the 20,000-dalton variant of human growth hormone (20K): evidence for a 20K-specific binding site.

The 20,000-dalton variant of human GH (20K) is known to circulate in blood, but few details are known about its plasma transport. A substantial portion of 20K appears to be protein bound despite its low affinity for the receptor-related GH-binding protein (BP). We, therefore, investigated the binding pattern of 20K in human plasma. Radioiodinated 20K was incubated with plasma or plasma fractions, and the mixture was fractionated by gel filtration. Saturation/Scatchard analysis was performed with both 20K and 22,000-dalton GH (22K). The majority (approximately 80%) of protein-bound 20K was complexed with a low affinity BP (Ka = approximately 2 x 10(5) M-1), with the remainder complexed with the high affinity2 receptor-related BP. The binding of 20K to the low affinity BP was specific for 20K; it may involve a 20K-specific binding site on the previously described low affinity plasma BP (peak I) or a separate 20K-specific BP. 22K did not interact with this binding site/BP. Analysis of the 20K-BP complex by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing suggested, but did not prove, the existence of a separate BP for 20K. We conclude that 20K in plasma binds primarily to a low affinity, 20K-specific binding site (possibly a new, third GH-BP), with only a small fraction bound to the GH receptor-related BP. This binding pattern is markedly different from that of 22K, which is predominantly bound to the receptor-related BP. The existence of a 20K-specific binding site/BP suggests an as yet unrecognized role for this GH variant.

Autoradiography↗
PubMed1990

Characterization of cardiovascular events mediated by platelet activating factor during systemic anaphylaxis.

Previous studies have shown that an anaphylactic reaction in the isolated perfused heart is characterized by drastic coronary constriction, arrhythmias, and severe impairment of contractility. In vivo anaphylaxis is associated with myocardial ischemia and rapid cardiovascular failure. Recently, not only histamine but also platelet activating factor (PAF) has been implicated in cardiac manifestation of anaphylaxis. The present study was designed to separate the effects of PAF from those of histamine on cardiovascular function during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous (s.c.) application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous (i.v.) infusion of ovalbumin were tested in anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced severe cardiac dysfunction. Within 3 min, cardiac output (CO) had already decreased by 90% and left ventricular end-diastolic pressure (LVEDP) increased significantly, indicating left ventricular pump failure. Concurrently, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of atrioventricular block. After 4 min, blood pressure (BP) rapidly decreased. All animals died within 10 min. Pretreatment with the H1-receptor antagonist mepyramine (1 mg/kg i.v.) in combination with the H2-receptor antagonist cimetidine (10 mg/kg i.v.) delayed onset of myocardial ischemia, arrhythmias and cardiac pump failure. After 10 min, however, LV contractility and BP steadily decreased, leading to severe hypotension within 30 min. If the selective PAF antagonist WEB 2086 (1 mg/kg i.v.) was administered in addition to cimetidine and mepyramine, myocardial ischemia and LV contractile failure were markedly inhibited further. In contrast, pretreatment with WEB 2086 alone had no beneficial effects on the anaphylactic cardiovascular changes. Therefore, we conclude that histamine is the predominant mediator during the early phase of systemic anaphylaxis whereas PAF-mediated effects are involved in cardiac dysfunction during the protracted late phase of anaphylaxis.

Anaphylaxis↗
PubMed1990

[Acute reduction of increased atrial natriuretic peptide level and cyclic guanosine monophosphate in patients with chronic heart failure caused by beta-adrenergic stimulation with dopexamine hydrochloride. Correlation with hemodynamic parameters].

In eight patients (63 +/- 8 years) with dilated cardiomyopathy, the acute effects of positive inotropic stimulation with dopexamine hydrochloride, a beta-2-agonistic and DA1-dopaminergic catecholamine, on the plasma levels of ANP and cGMP were tested. A four-point dose-response curve was prepared for dopexamine from 1 microgram/kg/min to 4 micrograms/kg/min. Each infusion stage lasted 15 min; ANP and cGMP were taken from the mixed venous blood. Hemodynamic parameters were determined by a Swan-Ganz catheter; cardiac output was determined by thermodilution. ANP dropped by 40% from 348 +/- 124 pg/ml to 208 +/- 70 pg/ml (p less than or equal to 0.01), while cGMP dropped by 25% from 4.8 +/- 1.6 pmol to 3.6 +/- 1.3 pmol/ml at the time of maximum hemodynamic effect after 1 h. Linear regression analyses revealed a significant relationship (p less than or equal to 0.01) between ANP as the independent variable and cGMP as the dependent variable. The hemodynamic determinants of the ANP concentration proved to be--independently of each other--the pulmonary capillary wedge pressure (p less than or equal to 0.01) and the mean right atrial pressure (p less than or equal to 0.01). The results show that chronically elevated ANP and cGMP levels can be strikingly reduced within a short time, whereby ANP and cGMP show similar kinetics. The results suggest a use of ANP and cGMP as humoral parameters in the therapy control of chronic heart failure.

Adrenergic beta-Agonists↗
PubMed1989

Low levels of high-affinity growth hormone-binding protein in African pygmies.

The cause of growth hormone resistance and short stature in African Pygmies in unknown. Low levels of insulin-like growth factor 1 that fail to respond to growth hormone suggest a possible deficiency of growth hormone receptors. The high-affinity growth hormone-binding protein is a fragment of the growth hormone receptor and may be an indicator of the number of receptors in tissues. We measured growth hormone-binding activity in plasma from 20 pygmies and 12 control subjects (7 white Americans and 5 non-Pygmy black Africans of normal stature). Growth hormone binding to the high-affinity binding protein was significantly reduced in the Pygmies as compared with the controls (mean +/- SD, 6.50 +/- 2.33 percent vs. 12.95 +/- 3.95 percent bound per 160 microliters of plasma; P less than 0.001); however, there was substantial overlap between the values for Pygmies and controls. Growth hormone binding to the low-affinity binding protein was similar in Pygmies and control subjects. We conclude that Pygmies have low levels of high-affinity growth hormone-binding protein in their plasma, which may indicate a reduced number of growth hormone receptors in their tissues. The finding may help explain the resistance to growth in Pygmies, but there may be additional reasons, related to the receptors or not, for their short stature.

Adolescent↗
PubMed1989

The function of plant heat shock promoter elements in the regulated expression of chimaeric genes in transgenic tobacco.

A series of deletion mutants of a soybean heat shock (hs) gene promoter was generated and linked to the chloramphenicol acetyl transferase (CAT) coding sequence. These chimaeric promoter/reporter gene constructs were introduced into tobacco and thermoregulated expression of CAT activity was examined in leaf extracts. Three different types of gene fusions were tested using two different BIN19 vector constructions: (1) translational fusion between the N-terminus of the protein coding sequence of the heat shock gene Gmhsp17.3-B and CAT; (2) transcriptional fusions between the 5' nontranslated RNA regions of Gmhsp17.3-B and CAT; and (3) promoter fusions joining the hs promoter upstream sequences to the TATA box sequence of the delta CaMV 35S-CATter vector. Alternatively, multiple copies of a synthetic deoxyoligonucleotide with the soybean hs consensus element (HSE2) were used. Heat inducible CAT activities were detected except in plants containing a transcriptional fusion devoid of all but 18 nucleotides at the 5' terminus of the hs gene transcript. CAT activity was detectable in these plants only during the recovery at 25 degrees C after a hs (40 degrees C). Overlapping HSE-like promoter sequences seem to be necessary for the induction of heat inducible transcription of linked genes; synthetic HSE2 sequences have the capacity to reconstitute a hs promoter in combination with a TATA box sequence. Effective translation during hs seems to require sequences in the 5' non-translated leader of the hs protein mRNA; these sequences can be functionally replaced by the 5' leader sequence of the delta CaMV 35S promoter.

Amino Acid Sequence↗
PubMed1989

Regulation of plasma growth hormone-binding proteins in health and disease.

Binding proteins (BP) for growth hormone (GH) have recently been discovered in human plasma. The main BP is related to the GH receptor and probably corresponds to the extracellular portion of the receptor. The BP influence several aspects of GH homeostasis and action. Their level and activity in blood, therefore, become important variables in overall GH physiology. However, to date little is known about the regulation of GH-BP in health and disease. To gain initial information about this point, GH-BP activity was examined in the plasma of 124 subjects with various physiologic and pathologic conditions. The conditions were selected to provide basic physiologic data (men, women, children, age, pregnancy and to investigate key disease states attended by abnormal GH physiology (liver cirrhosis, uremia, infection, acromegaly). A standardized GH binding assay was used to measure BP activity as an index of BP levels. Both the principal, high affinity BP (peak II) and the minor, low affinity BP (peak I) showed considerable individual variation in all groups. Neonates had the lowest levels of both BPs, but by the age of 1 year the levels had increased and remained fairly stable through the seventh decade. In males but not females between the ages of 1 and 20 years, the main (peak II) BP showed a slight upward trend, whereas the minor (peak I) BP declined moderately. Patients with cirrhosis showed the most variation in both BP, and uremic patients demonstrated decreased peak II, but not peak I, binding. Neither BP was affected in acromegaly. We conclude that BP activity in plasma is well conserved in most conditions, but substantial individual variability exists. BP activity increases dramatically during the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗