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Biomedical subjects

G Wagner

Publications and source records attributed to G Wagner.

At least 415 records · Page 23Linked to original sources

Summary of short- and long-term studies with bisoprolol in coronary heart disease (CHD).

This report summarizes the most important results of 11 studies regarding efficacy and safety of bisoprolol in patients with stable angina pectoris due to coronary heart disease. Assessments carried out 2-3 h after the administration of the beta 1-selective adrenoceptor blocking agent bisoprolol revealed that the dose of 10 mg produced maximum effects in terms of improvement of exercise capacity (W X min) and reduction of ST segment depression at peak exercise. Duration of action was maintained over 24 h after administration of 5 and 10 mg bisoprolol. Thus, the data indicate no relevant loss of effect 24 h after single or repeated administration of 5-20 mg/day. Open uncontrolled long-term studies over 1 year demonstrated that bisoprolol in the dose range of 5-20 mg once daily is safe and highly effective. The evaluation was based on the bisoprolol effects on bicycle exercise tests, weekly anginal attack rates, the incidence of untoward side effects, and clinical routine laboratory investigations.

Adrenergic beta-Antagonists↗

Primary aldosteronism due to a malignant ovarian tumour.

The case of a woman with autonomous aldosteronism, hypertension, and malignant ovarian tumour is reported. Hormone studies revealed high plasma aldosterone levels, and low plasma renin concentration. Following surgical removal of a malignant sex cord stromal tumour, the hyperaldosteronism regressed, and the hypertension improved. Subsequently the tumour recurred, as did hyperaldosteronism.

Aldosterone↗

Primary and secondary chloride transport in Halobacterium halobium.

Chloride uptake in intact cells of Halobacterium halobium was characterized by rates of influx and efflux of 36Cl- under conditions of light, respiration, or both. Halobacterial mutant strains with and without retinal transport proteins allowed study of the effects of halorhodopsin and bacteriorhodopsin under illumination. Two structurally independent chloride transport systems could be distinguished: halorhodopsin, the already known light-driven chloride pump, and a newly described secondary uptake system, which was energized by respiration or by light via bacteriorhodopsin.

Adenosine Triphosphate↗

[Synthesis of N-alpha-(arylsulfonyl-L-prolyl)- and N alpha-(benzyloxycarbonyl-L-prolyl)-D,L-4-amidinophenylalanine amides as inhibitors of thrombin].

N alpha substituted 4-cyanophenylalanines were prepared by reaction of the acid chloride, the activated ester and the mixed anhydride of Tos-Pro-OH, 2-naphthylsulfonyl-L-proline and Z-Pro-OH, respectively, with cyanophenylalanine. These acids were transferred into the amides via the 4-nitrophenyl esters or the mixed anhydrides. The cyano compounds were converted via the thioamides and the thioimidic esters into the amidines by common way. The exchange of the glycine residue by prolin in compounds former described caused a decreased antithrombin effect.

Chemical Phenomena↗

Absorption of menstrual discharge by tampons inserted during menstruation: quantitative assessment of blood and total fluid content.

The simultaneous absorption of genital secretions and blood was assessed in 61 intravaginal tampons from eight young, healthy, nulliparous volunteers during menstruation. The tampons were self-inserted over the first 3 days of menstruation according to the habit of each subject. Wide variations in the amount of blood and fluid absorbed were noted within and between subjects. The mean amount of genital secretion absorbed was 0.31 g/h and that of menstrual blood was 0.76 g/h. The average tampon absorbed 65% blood and 35% genital secretion.

Absorption↗

[Synthesis of N-alpha-(tosylglycylprolyl)-4-amidinophenylalanine amides as thrombin inhibitors].

N alpha-(Tosylprolylglycyl)-4-cyanphenylalanine was synthesized by the reaction of an activated ester and a mixed anhydride, respectively, of Tos-Pro-Gly-OH with 4-cyanophenylalanine. N alpha-(Tosylglycylprolyl)-4-cyanophenylalanine was prepared by reaction of Tos-Gly-Cl with N alpha-prolyl-4-cyanophenylalanine. These acids were transferred into the amides. The cyano compounds were converted into the desired amidines via the thioamides and the thioimidic esters.

Amidines↗

[Abdominal computerized tomography in the after-care of ovarian cancers].

The diagnostic capacity of abdominal CT as a follow-up in ovarian cancer is demonstrated on 67 patients verified by a second-look operation. In the diagnosis of recurrence CT has a sensitivity of 83%, a specificity of 94% and an overall accuracy of 88%. With local recurrence or residual tumours CT has an accuracy of 91%, with liver metastases of 94%. The accuracy in finding peritoneal carcinosis is 84%. Ascites proved to be a sure sign of peritoneal carcinosis. Because of its high sensitivity second-look operation can be avoided in case of a positive report. In a negative report a second-look operation will be necessary to verify the success of therapy. In the follow-up of ovarian cancer CT should be performed every 6 month during the first 2 years and yearly for another 3 years.

Female↗

Amide proton exchange in proteins by EX1 kinetics: studies of the basic pancreatic trypsin inhibitor at variable p2H and temperature.

With the use of one-dimensional 1H nuclear magnetic resonance, two-dimensional correlated spectroscopy, and two-dimensional nuclear Overhauser enhancement spectroscopy, the exchange mechanisms for numerous individual amide protons in the basic pancreatic trypsin inhibitor (BPTI) were investigated over a wide range of p2H and temperature. Correlated exchange under an EX1 regime was observed only for the most slowly exchanging protons in the central hydrogen bonds of the antiparallel beta-sheet and only over a narrow range of temperature and p2H, i.e., above ca. 55 degrees C and between p2H 7 and 9, where the opening rates of the structure fluctuations which promote the exchange of these protons are of the order 0.1 min-1. At p2H below 7, the exchange of this most stable group of protons is uncorrelated and is governed by an EX2 mechanism. At p2H above 9, the exchange is also uncorrelated and occurs via either EX2 or EX1 processes promoted by strictly local structure fluctuations. For all other backbone amide protons in BPTI, the exchange was found to be uncorrelated and by an EX2 mechanism under all conditions of p2H and temperature where quantitative measurements could be obtained with the methods used, i.e., for kex approximately less than 5 min-1. From these observations with BPTI it can be concluded that the amide proton exchange in globular proteins is quite generally via EX2 processes, with rare exceptions for measurements with extremely stable protons at high temperature and basic p2H. This emphasizes the need for further development of suitable concepts for the structural interpretation of EX2 amide proton exchange [Wagner, G. (1983) Q. Rev. Biophys. 16, 1-57; Wagner, G., Stassinopoulou, C. I., & Wüthrich, K. (1984) Eur. J. Biochem. 145, 431-436] and for more detailed investigations of the intrinsic exchange rates for solvent-exposed amide protons in the "open" states of a protein [Roder, H., Wagner, G., & Wüthrich, K. (1985) Biochemistry (following paper in this issue)].

Amides↗

Individual amide proton exchange rates in thermally unfolded basic pancreatic trypsin inhibitor.

A novel experiment is described for measurements of amide proton exchange rates in proteins with a time resolution of about 1 s. A flow apparatus was used to expose protein solutions in 2H2O first to high temperature for a predetermined time period, during which 1H-2H exchange proceeded, and then to ice-water. The technique was applied for exchange studies in thermally unfolded, selectively reduced basic pancreatic trypsin inhibitor. Measurements were made by 1H nuclear magnetic resonance after the exchange was quenched by rapid cooling. Thereby, the sequence-specific resonance assignments for the folded protein could be used, which had been previously obtained. The results of this study indicate that the exchange rates in the thermally unfolded protein are close to those expected for a random chain and that the NH exchange is catalyzed by 2H+ and O2H- up to high temperature, with no significant contributions from p2H-independent catalysis. We conclude that the parameters derived by Molday et al. [Molday, R. S., Englander, S. W., & Kallen, R. G. (1972) Biochemistry 11, 150-158] from measurements with small model peptides can be used to calculate intrinsic exchange rates in unfolded proteins and thus provide a reliable reference for the interpretation of exchange rates measured under native conditions.

Amides↗

Comparison of ouabain receptors in sheep myocardium and Purkinje fibres.

The conducting system of the heart has been reported to be more sensitive to the toxic effects of digitalis than the working myocardium. To investigate the molecular basis of these observations, we have characterized the ouabain receptor in Purkinje fibres and ventricular muscle of the digitalis-sensitive sheep heart using cell membrane preparations, crude homogenates and contracting heart tissues. [3H]-Ouabain binding has the following characteristics: in sheep left ventricular cell membranes, specific binding was of high affinity (KD 1.9 X 10(-9) M at 37 degrees); was co-incident with an inhibition of (Na+ + K+)-ATPase activity; and was inhibited by K+ and unlabelled cardiotonic steroids; in crude homogenates, the maximal binding capacity but not the affinity for ouabain varied in different parts of the sheep heart with Purkinje fibres containing markedly fewer binding sites (0.33 X 10(14)/g wet weight; left ventricle, 1.3 X 10(14)/g wet weight) and in isolated, contracting Purkinje fibres and right ventricular moderator band strips, concentration-response curves for [3H]-ouabain binding, increase in force of contraction and inhibition of [86Rb+]-uptake were co-incident. In both contracting tissues, a ouabain concentration of 3 X 10(-7) M occupied about 50% of the specific binding sites, gave the maximal inotropic effect without toxicity and inhibited [86Rb+]-uptake by about 50%. The maximal binding capacity was lower in contracting Purkinje fibres (2 X 10(14) binding sites/g wet weight) than in contracting moderator band strips (3.9 X 10(14) binding sites/g wet weight). The maximal inotropic effects were reached slightly faster in Purkinje fibres but toxicity also occurred faster in these fibers. We conclude that the specific ouabain binding site is the receptor mediating positive inotropy and inhibition of (Na+ + K+)-ATPase in the sheep heart. Further, this receptor is identical in both the conducting system and working myocardium but the conducting system contains many fewer receptors. This change in receptor number, rather than affinity, may underlie the increased ouabain toxicity observed in Purkinje fibres.

Animals↗

Systematic application of high-resolution, phase-sensitive two-dimensional 1H-NMR techniques for the identification of the amino-acid-proton spin systems in proteins. Rabbit metallothionein-2.

Novel strategies for elucidation and classification of amino acid 1H-NMR spin systems in proteins were developed exploiting recently introduced two-dimensional NMR techniques such as phase-sensitive double-quantum-filtered correlated spectroscopy, relayed coherence transfer spectroscopy, double quantum spectroscopy and nuclear Overhauser spectroscopy. Due to the improved resolution in phase-sensitive spectra, the fine structure of cross peaks could be exploited as a powerful source of information for establishing 1H-1H connectivities. Principles for the interpretation of multiplet structures of absorption mode cross peaks are discussed. With these methods the 1H spin systems of rabbit liver metallothionein-2 were elucidated and classified according to amino acid types. Despite the intrinsically difficult situation arising from the unusual amino acid composition of this protein, a more complete characterization of the 1H spin systems prior to the step of sequential resonance assignments was achieved with the presently introduced methodology than was possible in earlier studies of proteins of similar size.

Amino Acids↗