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G Baumann

Publications and source records attributed to G Baumann.

At least 289 records · Page 16Linked to original sources
PubMed1989

In vivo kinetics of a covalent growth hormone-binding protein complex.

The biologic function of the newly recognized binding proteins (BP) for human growth hormone (hGH) in human plasma is largely unknown; hGH circulates in part in complexed form in association with the BP. In a previous study we showed that the in vivo kinetics of hGH were altered in the presence of the BP. However, that study gave only qualitative information because the BP was present in excess and the complex was subject to dissociation in vivo. To gain more quantitative information about the in vivo behavior of complexed hGH, metabolic clearance (MCR), distribution volume (Vd), and degradation rate of a covalently crosslinked, stoichiometrically correct, chemically stable hGH-BP complex were measured. The MCR and the degradation rate of complexed hGH were tenfold lower than those of free hGH (P less than .001), and its Vd was significantly smaller than that for free hGH (P less than .001). The covalent complex was fully immunoreactive with polyclonal anti-hGH antibodies. We conclude that complexed hGH is protected from clearance and degradation by being restricted from access to degradation sites, including the proximal renal tubule and receptor-mediated delivery to intracellular proteolygic organelles. The data developed also yield preliminary information about the in vivo distribution of the BP itself. These data provide important guidelines for future studies regarding the in vivo effects of the BP. In addition, the results indicate that the principal epitope(s) of hGH remain(s) exposed on the outer surface of the complex.

Animals↗
PubMed1989

Polarity as a criterion in protein design.

Hypothetical proteins can be tested computationally by determining whether or not the designed sequence-structure pair has the characteristics of a typical globular protein. We have developed such a test by deriving quantities with approximately constant value for all globular proteins, based on empirical analysis of the exposed and buried surfaces of 128 structurally known proteins. The characteristic quantities that best appear to segregate badly designed or deliberately misfolded proteins from their properly folded natural relatives are the polar fraction of side chains on the protein surface and, independently, in the protein interior. Three of the seven hypothetical structures tested here can be rejected as having too many polar side-chain groups in the interior or too few on the protein surface. In addition, a recently designed nutritional protein is identified as being very much unlike globular proteins. These database-derived characteristic quantities are useful in screening designed proteins prior to experiment and may be useful in screening experimentally determined (X-ray, NMR) protein structures for possible errors.

Electric Conductivity↗
PubMed1989

Effect of intravenous pimobendan (UDCG 115 BS) on hemodynamics and left ventricular volumes in idiopathic dilative cardiomyopathy.

Acute cardiovascular effects of 5 mg (group I, n = 6) and 10 mg (group II, n = 6) intravenous pimobendan (UDCG 115 BS) were studied by right and left heart catheterizations in patients suffering from idiopathic dilative cardiomyopathy (NYHA II and III). Before and 2.5 h after application of pimobendan, left ventricular volumes and left ventricular dP/dtmax were evaluated by left heart catheterization. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCP), cardiac output (CO), heart rate (HR), and sytemic blood pressure (BP) were assessed before and 2.5, 4, and 6 h after administration of pimobendan. PCP was reduced from 12.2 +/- 7.5 to 8.3 +/- 7.1 mm Hg (p less than 0.05) by 5 mg pimobendan, and from 18.3 +/- 6.2 to 6.2 +/- 3.4 mm Hg (p less than 0.005) by 10 mg pimobendan. Reduction of RAP was only significant in group II (6.2 +/- 3.2 to 1.2 +/- 0.9 mm Hg; p less than 0.05). In contrast to other hemodynamic parameters, the significant increase of CO exhibited no dose dependency. Only at 10 mg pimobendan induced a temporary reduction of mean arterial blood pressure (MAP). An increase in HR occurred only in group I and was merely transient. Left ventricular end-diastolic (EDVI) and end-systolic volume (ESVI) indices were clearly reduced by 5 mg, as well as by 10 mg pimobendan. However, a significant rise of left ventricular ejection fraction (EF) only occurred in group II. On the other hand, left ventricular dP/dtmax was increased significantly in both groups. No adverse effects were noted during acute administration of pimobendan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cardiovascular profile of UDCG 115 BS-pimobendane and reversibility of catecholamine subsensitivity in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy.

The pyridazoline derivative UDCG 115 BS (pimobendane) is a new, noncatecholamine, nonglycoside inotropic compound with potent vasodilative properties which exerts its stimulatory myocardial effect by increasing the Ca2+ affinity of cardiac contractile proteins and thus improving Ca2+ utilization. The aim of this study was to characterize and quantify the hemodynamic profile of oral UDCG 115 BS in 25 patients suffering from idiopathic congestive cardiomyopathy (NYHA III) and compare these effects with the action of the beta 1-receptor agonist dobutamine. UDCG 115 BS 5 mg p.o. increased cardiac output, cardiac index, and stroke volume index by approximately 60%. With only minor changes in heart rate, ventricular filling pressures decreased by 40%. A decline in pulmonary and systemic vascular resistance (-50%), as well as in systolic, diastolic, and mean pulmonary artery pressures (-35%) were also observed. The effects of 5 mg UDCG 115 BS were comparable to those that occurred with the optimal dose of dobutamine, whereas 10 mg UDCG 115 BS induced significantly more pronounced hemodynamic changes. The effects of UDCG lasted for at least 12 h. No major side effects were observed. Continuous treatment with 10 mg UDCG 115 BS/day for greater than 5 days resulted in a significantly improved response in beta-adrenoceptor stimulation as well as a drop in endogenous plasma catecholamines to nearly normal values. We therefore conclude that UDCG 115 BS, with its unique receptor-independent mechanism of action, may represent a new therapeutic approach in the management of patients with congestive heart failure (CHF).

Blood Pressure↗
PubMed1989

Clinical efficacy of pimobendan (UD-CG 115 BS) in patients with chronic congestive heart failure.

The pyridazoline derivative UD-CG 115 BS (pimobendan) is a noncatecholamine, nonglycoside new inotropic compound with potent vasodilator properties that exerts stimulatory myocardial effects by increasing the Ca2+ affinity of cardiac contractile proteins, thus improving Ca2+ utilization. The aim of the present study was to characterize and quantify the hemodynamic effects of oral UD-CG 115 BS in 25 patients with idiopathic congestive cardiomyopathy (NYHA stage III) and compare these to the action of the beta 1-receptor agonist dobutamine. UD-CG 115 BS 5 mg p.o. increased cardiac output, cardiac index, and stroke volume index by approximately 60%. With only minor changes in heart rate, ventricular filling pressures decreased (-40%) and there was a decline in pulmonary and systemic vascular resistance (-50%), as well as in systolic, diastolic, and mean pulmonary artery pressure (-35%). The effects of 5 mg UD-CG 115 BS were comparable to the optimal dose of dobutamine, while 10 mg induced significantly more pronounced hemodynamic changes. The effects of UD-CG 115 BS lasted for at least 12 h. No major side effects were observed. A continuous treatment with 10 mg of UD-CG 115 BS/day over a period of 5 days resulted in a significantly improved response to beta-adrenoceptor stimulation while endogenous plasma catecholamines fell down to nearly normal values. It is concluded that UD-CG 115 BS, with its unique receptor independent mechanism of action, may represent a new therapeutic approach for management of congestive heart failure patients.

Adult↗
PubMed1989

[Acute and chronic effects of UDCG 115 BS (pimobendan) in patients with advanced myocardial failure].

In a double-blind, placebo-controlled cross-over study acute hemodynamic effects of oral UDCG 115 BS (5 and 10 mg) were investigated in myocardial heart failure before (n = 16) and after (n = 13) chronic treatment (4 weeks). Before chronic treatment, UDCG 115 BS induced a similar increase in cardiac index with both doses (5 mg: from 2.4 +/- 0.7 to 3.5 +/- 0.7 l/min/m2, p less than 0.001; 10 mg: from 2.5 +/- 0.6 to 3.6 +/- 0.9 l/min/m2, p less than 0.001). Both right atrial pressure and pulmonary capillary wedge pressure were clearly reduced (p less than 0.001). Heart rate increased slightly only after 5 mg (p less than 0.05). Systemic vascular resistance was reduced (p less than 0.001), whereas mean blood pressure did not change. After chronic treatment (2 x 5 or 2 x 10 mg/d) and cessation of medication for 24 h there was no difference for control hemodynamic values as compared to placebo. Acute hemodynamic effects were considerably attenuated in comparison with the results obtained before chronic treatment. NYHA-classification, however, clearly (p less than 0.05) improved during administration of UDCG 115 BS as compared to placebo. Two patients died on placebo, whereas no patient expired on verum. This might indicate a therapeutic longterm effect of UDCG 115 BS, despite the observed development of partial tolerance.

Adult↗
PubMed1988

[5-year follow-up after endarterectomy of carotid artery thrombosis].

The long-term results of carotid endarterectomy were analysed in 119 patients, operated on between January 1979 and December 1980 (135 endarterectomies; preoperative data analysed retrospectively). 43 patients had been in stage I, 39 in stage IIa, 13 in stage IIb, 4 in stage III, and 20 in stage IV. Perioperative mortality was 0.8%, while hospital mortality was 2.5%. Transitory perioperative neurological deficits occurred in 4.2% of all patients, but no permanent ones. Five years postoperatively 44.5% had died, nearly half (43.4%) of cardiovascular disease. Cerebrovascular disease and tumour each caused 15% of deaths. During the five-year follow-up period 12% of all patients had had transitory ischaemic attacks; 16% had suffered a stroke (in 63% on the operated side). With a high prevalence of risk factors, only the quality of diabetic control (mortality rate of well controlled diabetes 38%, of poorly controlled 70%) and the risk factors heart failure and vascular occlusive disease had a significant influence on the mortality rate. But the mortality rate was significantly lowered with the use of platelet aggregation inhibitors (41.6% vs 72.7%).

Adult↗
PubMed1988

Immunochemical similarity of the human plasma growth hormone-binding protein and the rabbit liver growth hormone receptor.

We probed the (immunochemical) relationship between the recently discovered growth hormone binding protein in human plasma and the growth hormone receptor using monoclonal and polyclonal antibodies raised against rabbit liver growth hormone receptor. The human binding protein was recognized by these antibodies; its immunological crossreactivity compared to the rabbit receptor was 1-2%. These data suggest a) that the binding protein and the receptor are structurally related and b) that rabbit and human growth hormone receptors share some but not all epitopes.

Animals↗
PubMed1988

Nucleotide sequence analysis of soybean small heat shock protein genes belonging to two different multigene families.

In soybean, the small heat shock proteins of 15 to 18 kDa are encoded in the nucleus by at least two different multigene families, designated class I and class VI. Genomic DNA sequences of two new heat shock genes and flanking regions were determined: Gmhsp18.5-C, a class I gene, and Gmhsp17.9-D, the first known class VI gene. Comparison of both genes revealed a moderate homology (approx. 38%) mainly within the 3' ends of their coding regions. Hydropathic characterizations and secondary-structure predictions of the deduced amino acid sequences revealed two conserved domains within the C-terminal halves of the polypeptides that are also present in related proteins of other organisms. The transcription of both genes is heat shock dependent and the mRNA start sites, as determined by S1 nuclease mapping, are located downstream from typical TATA box sequences and multiple heat shock promoter elements such as 5' CT-GAA--TTC-AG. The putative promoter regions of the genes are preceded by long tracts of repetitive sequences with a high A + T content of 79 to 89%, which are bordered by runs of "simple sequences" such as (A) 12/13, (T)10 and (TA)10. Similar characteristic features are present in the promoter and 5'-flanking regions of other soybean heat shock genes. The possible function of these distinct sequences is discussed.

Amino Acid Sequence↗
PubMed1988

Comparison of acute haemodynamic effects of dopexamine hydrochloride, dobutamine and sodium nitroprusside in chronic heart failure.

Dopexamine hydrochloride (Dopacard) is a new synthetic catecholamine compound, which possesses potent beta 2-adrenergic and DA1-dopaminergic agonistic properties. It is free of alpha-adrenergic activity, has no beta 1-adrenergic activity and is less potent at DA2-dopaminergic receptors than dopamine. In the present study the acute haemodynamic effects of dopexamine hydrochloride were compared to those of dobutamine and nitroprusside in 12 patients with idiopathic congestive cardiomyopathy in an open crossover study. With dopexamine hydrochloride, there were dose-dependent increases from control in cardiac output and stroke volume, decreases in blood pressure, right and left atrial pressure, systemic vascular resistance and pulmonary vascular resistance and little change in heart rate. Similar effects were seen with nitroprusside, apart from a marked increase in heart rate, and with dobutamine, except that systolic aortic blood pressure increased and there was no change in diastolic or mean pressure or pulmonary artery systolic pressure. In general, dopexamine hydrochloride produced effects between those produced by the other two treatments. This suggests that dopexamine with its combined vasodilator and inotropic action has a desirable cardiovascular profile with advantages over the beta 1-receptor agonist dobutamine and the pure vasodilator sodium nitroprusside.

Adult↗
PubMed1988

MK 458, a selective and potent D2 receptor agonist in advanced Parkinson's disease.

MK 458 is a potent and selective D2 receptor agonist. MK 458 consists of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) in a hydroxypropyl-methylcellulose-lactose matrix. MK 458, mean dose 8.1 mg (range 2.5 to 13.5 mg), was administered to 14 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The duration of the study was 4 weeks with a titration to maximum dose in 2 weeks. The addition of MK 458 resulted in a mean reduction in levodopa of 41% (range 0 to 81%). This degree of levodopa reduction was not seen in previous studies with other DA agonists. While the reduction in signs of PD was comparable to those on levodopa, MK 458 did not induce dyskinesias or dystonias. It is postulated that MK 458 may be able to replace levodopa as the primary treatment for PD.

Adult↗
PubMed1988

The circulating growth hormone (GH)-binding protein complex: a major constituent of plasma GH in man.

The recent discovery of a specific binding protein for human GH (hGH) in human plasma suggests that hGH circulates in part as a complex in association with the binding protein(s). However, the magnitude of the complexed fraction prevailing under physiological conditions is unknown because of 1) dissociation of the complex during analysis and 2) potential differences in the binding characteristics of radiolabeled and native hGH. We conducted experiments designed to minimize dissociation during analysis (gel filtration in prelabeled columns, frontal analysis, and batch molecular sieving) with both native and radioiodinated hGH. All three methods yielded similar estimates for the complexed fraction. In normal plasma the bound fraction for 22 K hGH averaged 50.1% (range, 39-59%), that for 20 K hGH averaged 28.5% (range, 26-31%). Above a hGH level of about 20 ng/ml the bound fraction declines in concentration-dependent manner due to saturation of the binding protein. We conclude that a substantial part of circulating hGH is complexed with carrier proteins. This concept has important implications for the metabolism, distribution, and biological activity of hGH.

Carrier Proteins↗
PubMed1988

A rapid and simple assay for growth hormone-binding protein activity in human plasma.

The newly discovered circulating growth hormone binding proteins dictate a re-evaluation of the state of GH in plasma in health and disease as the binding proteins are known to affect GH metabolism and action. We describe a rapid and simple GH-binding assay that allows determination of free and complexed plasma GH, as well as GH-binding protein activity as an index of GH-binding protein levels, with relative ease. The method is based on incubation of plasma with 125I-GH and separation of bound from free GH on small DEAE-cellulose columns; it can be used on a large scale for routine determinations. The results obtained by this method are comparable to those obtained with the previously used slow and more cumbersome gel filtration technique. Initial data obtained in normal subjects and certain disease states show that the bound fraction of plasma GH is similar in men, women and children, is unaffected by pregnancy or acute infection, but is marginally decreased in liver cirrhosis. In acromegaly, binding protein activity also appears normal when allowance is made for partial saturation of the binding proteins by the high prevailing GH levels. The technique we describe should facilitate investigations of normal and abnormal regulation of the GH binding proteins.

Adolescent↗
PubMed1988

Plasma estrogens, androgens, and von Willebrand factor in men on chronic hemodialysis.

The role of sex hormones in atherogenesis has not been well defined. Since hemodialysis patients show signs of feminization and an increased propensity for atherosclerosis they are particularly suited to probe the relationship between estrogen, testosterone, and atherosclerosis. Therefore, we measured plasma total, free, and protein-bound estradiol (E2), testosterone (Te), and prolactin in 28 hemodialysis patients and in 30 age-matched controls. Von Willebrand factor (vWF) levels were also assayed. Total and free E2 as well as Te were significantly decreased in the patients (p less than 0.001). However, the E2/Te ratio was elevated in the patients (p = 0.05), as was vWF (p less than 0.01). No correlations were found between hormone levels and vWF, gynecomastia or vascular disease, but vWF and vascular disease were highly correlated. We conclude that in hemodialysis patients absolute estrogen levels are lower than normal, but that the estrogen/androgen ratio is shifted in favor of estrogen because of the coexistence of androgen deficiency. These findings suggest that an elevation in the estrogen/androgen ratio, rather than an increase in estrogen per se, may be a risk factor for atherosclerosis.

Adult↗
PubMed1987

[Fibrinolytic treatment of deep venous thromboses with streptokinase at an ultrahigh dosage].

Twenty-one patients with deep vein thrombosis were treated for six hours per day in accordance with an "ultrahigh" dose scheme with 1,500,000 units/hour streptokinase. A maximum of two such cycles were administered in the first ten patients, and the subsequent patients received up to five cycles as required. In terms of clinical chemical parameters, a pronounced lowering of fibrinogen with corresponding elevation of fibrin(ogen) cleavage products regularly occurred during the first cycle. There were great differences in the individual times for which these alterations persisted (12-72 hours). The alterations during the subsequent cycles were very much less, probably because of the pronounced lowering of the plasminogen concentration. The clinical tolerance (including hemorrhagic complications) was roughly comparable with that of a streptokinase treatment with conventional doses. Phlebographic checking of the result of treatment showed that the ultrahigh dosed intermittent dosage scheme is a highly effective treatment procedure with which the duration of treatment can be appreciably shortened compared to conventional dosage schemata: in four cases, a full recanalization could already be attained after a single cycle.

Adolescent↗
PubMed1987

Functional analysis of sequences required for transcriptional activation of a soybean heat shock gene in transgenic tobacco plants.

The 5' DNA sequences involved in the thermal inducibility of the soybean heat shock gene hs6871 were analysed in transgenic tobacco plants. The transcriptional activity of various in vitro generated deletion mutants was examined by Northern blot analysis, S1 nuclease mapping and dot-blot hybridization. At least 181 bp upstream from the translational start site are sufficient for thermal induction at 40 degrees C and correct initiation of transcripts. Full promoter activity with the induction of wild-type levels of transcripts requires additional upstream sequences contained within 439 bp 5' to the coding sequence. Our results suggest that faithful regulation and the generation of high levels of hs6871-specific mRNA depend on the presence of sequences which show homology to the 14-bp heat shock consensus element of Drosophila and, in addition, on as yet unidentified enhancer-like upstream sequences.

Journal Article↗
PubMed1987

Community hospital administration of intravenous tissue plasminogen activator in acute myocardial infarction: improved timing, thrombolytic efficacy and ventricular function.

As an investigational fibrinolytic agent for acute myocardial infarction, intravenous recombinant tissue-type plasminogen activator (rt-PA) has been administered primarily in tertiary care and university centers. To determine the value of early initiation of such therapy, two satellite community hospital emergency rooms were established for use of rt-PA and the experience was compared among 142 consecutive patients who were transferred to a regional center for acute cardiac catheterization after intravenous rt-PA therapy. In Group I (n = 19), patients received rt-PA after interhospital transport to the regional center, but before cardiac catheterization. In Group II (n = 70), rt-PA therapy was initiated by the helicopter physician and nurse team after their arrival at the local community hospital emergency room. Group III patients (n = 53) had rt-PA administered in the local community hospital by the emergency room physician. Group III patients had earlier initiation of therapy (2.1 +/- 0.8 hours in Group III versus 3.8 +/- 1.2 hours in combined Groups I and II, p less than 0.001) and an increased rate of infarct vessel recanalization on the 90 minute coronary angiogram (81 in Group III versus 67% in combined Groups I and II, p = 0.057). The patients in Group III had a higher acute left ventricular ejection fraction (54 +/- 8% versus 50 +/- 9.5% in combined Groups I and II, p less than 0.01) and a trend toward an increased 7 day ejection fraction (55.5 +/- 9% versus 51.7 +/- 9.5%, respectively, p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗