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Biomedical subjects

G Wagner

Publications and source records attributed to G Wagner.

At least 379 records · Page 21Linked to original sources
PubMed1987

Protein structures in solution by nuclear magnetic resonance and distance geometry. The polypeptide fold of the basic pancreatic trypsin inhibitor determined using two different algorithms, DISGEO and DISMAN.

A set of conformational restraints derived from nuclear magnetic resonance (n.m.r.) measurements on solutions of the basic pancreatic trypsin inhibitor (BPTI) was used as input for distance geometry calculations with the programs DISGEO and DISMAN. Five structures obtained with each of these algorithms were systematically compared among themselves and with the crystal structure of BPTI. It is clear that the protein architecture observed in single crystals of BPTI is largely preserved in aqueous solution, with local structural differences mainly confined to the protein surface. The results confirm that protein conformations determined in solution by combined use of n.m.r. and distance geometry are a consequence of the experimental data and do not depend significantly on the algorithm used for the structure determination. The data obtained further provide an illustration that long intramolecular distances in proteins, which are comparable with the radius of gyration, are defined with high precision by relatively imprecise nuclear Overhauser enhancement measurements of a large number of much shorter distances.

Algorithms↗
PubMed1987

Metal co-ordination in rat liver metallothionein-2 prepared with or without reconstitution of the metal clusters, and comparison with rabbit liver metallothionein-2.

Possible origins of the different metal co-ordination topologies in the recently determined structures of rat metallothionein-2 (MT2) in single crystals and rabbit MT2 in solution were investigated. A complete structure determination for rat MT2 in solution by nuclear magnetic resonance (n.m.r.) showed that the differences in the spatial structures cannot be attributed to the different primary structures of the two species. Comparison of [113Cd7]MT2 obtained by reconstitution of the apoprotein in vitro with preparations using a different procedure showed, moreover, that the metal co-ordination observed in solution by n.m.r. is not an artefact of the protein reconstitution. Solutions of high-pressure liquid chromatographically homogeneous biosynthetic preparations of [113Cd, Zn]MT2 were obtained from rat liver following injection of 113Cd into rats in vivo, without further metal exchange after protein isolation. They contain a mixture of several forms of MT2 with different relative metal compositions, giving rise to an increased number of 113Cd resonances. For the components of the four-metal cluster, the major one of these different forms exhibits patterns in the two-dimensional [1H, 113Cd]-correlated spectra that are indistinguishable from those of [113Cd7]MT2, thereby implying identity of cluster coordination and topology. These results are discussed with regard to continued investigations into the differences between the solution structure and crystal structure of MT2.

Amino Acid Sequence↗
PubMed1987

Reinvestigation of the aromatic side-chains in the basic pancreatic trypsin inhibitor by heteronuclear two-dimensional nuclear magnetic resonance.

The 1H nuclear magnetic resonance (n.m.r.) assignments for the aromatic spin systems of the four tyrosines and four phenylalanines in the basic pancreatic trypsin inhibitor (BPTI) were reinvestigated using novel 13C-1H heteronuclear two-dimensional experiments. Resonance lines which are degenerate in homonuclear 1H n.m.r. spectra could thus be resolved. Based on this new evidence the previous assignments for Phe22 and Phe33 had to be corrected. This affects the earlier conclusions on aromatic ring flips in BPTI in that Phe22 is rotating rapidly on the n.m.r. time scale at 36 degrees C, rather than being immobilized up to 80 degrees C.

Amino Acid Sequence↗
PubMed1987

[Estrogen-induced gynecomastia following use of estrogen-containing local agents].

Loss of libido, decreased hair growth and gynecomastia developed in a 61-year-old man after six months of applying an estrogen-containing hair tincture for diffuse alopecia areata of the head hair. All these signs disappeared within four weeks of stopping the application, and hormone levels were again normal. Locally applied estrogen preparations are in general contraindicated in males because of their potential systemic effects. If they have to be given, hormone levels (testosterone; estradiol) must be checked.

Alopecia↗
PubMed1987

Stereospecific assignments of side-chain protons and characterization of torsion angles in Eglin c.

Stereospecific assignments were obtained in the protein Eglin c for beta-methylene protons of 9 out of the 24 residues with AMX symmetry, for three residues with long side chains and for the gamma-methyl groups of 8 out of the 11 valines. This was achieved by analyzing the cross-peak multiplet structures in two-dimensional correlated spectra with spectral simulations and peak fitting, and by quantitative measurements of intraresidue nuclear Overhauser enhancements. In addition to the stereospecific assignments, information on the torsion angles phi and chi 1 was obtained. To estimate inferences of internal motions on this analysis, the effect of uniform averaging within a certain range of the torsion angle chi 1 on cross-peak multiplet structures and on relative intraresidue nuclear Overhauser enhancement is discussed.

Magnetic Resonance Spectroscopy↗
PubMed1987

[Pityriasis versicolor pseudoatrophicans. A case description].

We report on a pseudoatrophic manifestation of tinea versicolor. A 32-year-old female patient, who had suffered from typical spotty lesions of tinea versicolor for 12 years, now additionally developed pseudoatrophic lesions within a few weeks. Complete remission of these lesions after local antimycotic therapy as well as mycological and histopathological findings confirmed the diagnosis of pseudoatrophic tinea versicolor.

Adult↗
PubMed1987

Assignment of the 13C nuclear magnetic resonance spectrum of a short DNA-duplex with 1H-detected two-dimensional heteronuclear correlation spectroscopy.

Proton-detected 1H-13C heteronuclear correlated spectroscopy [( 1H,13C]-COSY) was used to establish relations between the carbon-13 and proton nuclear magnetic resonance chemical shifts in the hexadeoxynucleoside pentaphosphate d-(GCATGC)2. Using the previously established sequence-specific proton NMR assignments, sequence-specific assignments were thus obtained for nearly all proton-bearing carbons. This approach offers a new criterion for distinguishing between the proton NMR lines of purines and pyrimidines, based on the different proton-carbon-13 coupling constants. Furthermore, the adenine ring carbon 2 has a unique carbon-13 chemical shift, which enables a straightforward identification of the adenine C2H resonances by [1H,13C]-COSY.

Base Sequence↗
PubMed1987

Spatial structure of rabbit liver metallothionein-2 in solution by NMR.

Sequence-specific assignments of the proton spin systems of (Cd7) rabbit liver metallothionein-2 were obtained with homonuclear two-dimensional nuclear magnetic resonance techniques. On the basis of the NMR data the amino acid sequence had to be modified in six positions, and it was found that the protein consists of 62 rather than 61 residues. Through-bond connectivities between the metals and sequentially assigned cysteine residues were obtained with two-dimensional heteronuclear 1H-113Cd correlated spectroscopy. This information, and distance constraints obtained from nuclear Overhauser enhancement spectra were used as input for distance geometry calculations of the spatial polypeptide fold. The polypeptide chain forms two domains which enclose a three-metal cluster and a four-metal cluster, respectively. The metal coordination within the clusters is markedly different from that of (Cd5, Zn2)-MT-2 from rat liver as determined by X-ray crystallography (Furey, et al., 1986) i.e. in the two structures different metal-cysteine combinations prevail for 5 of the 12 connectivities in the three-metal cluster and for 14 of the 16 connectivities in the four-metal cluster.

Amino Acid Sequence↗
PubMed1987

[Comparison between prostaglandin E2 gel and oxytocin in medically indicated labor induction].

The use of prostaglandins (PG) increasingly replaces the "classical" method of induction of labour by means of oxytocin and amniotomy, the last-named method being associated, especially in women with an unripe cervix, with side effects like prolonged labour and a higher rate of obstetric surgery. In this study the point of interest was whether prostaglandins offer any advantages over the classical method in respect of efficacy and maternal and foetal tolerance. 99 patients subdivided into primiparae and multiparae were randomly assigned to group A or B. In group A labour was induced with 1 mg resp. 2 mg PGE2 intravaginally at an interval of 6 hours. In group B the method of induction consisted of intravenous oxytocin and amniotomy. The success rate of induction was almost equal in both groups. However, in those patients where PGE2 induction did not succeed and who could not be delivered within 12 hours the cervical score was significantly improved in comparison to the oxytocin group. Based on the experience reported in the literature, one might speculate that an increased dosage could still improve the results of vaginally administered PGE2 gel.

Administration, Intravaginal↗
PubMed1987

Comparison of the effects of two doses of bisoprolol on exercise tolerance in exercise-induced stable angina pectoris.

Recently, bisoprolol has been investigated regarding its effects on exercise tolerance and the duration of action in patients with coronary heart disease (CHD) following single oral administration. It appears, however, that the extent of effects of 5 mg bisoprolol is not fully established yet. Therefore, the effects of 5 and 10 mg bisoprolol and the duration of action were assessed in 12 patients (10 male, 2 female; mean age 60.2 years) with stable angina pectoris due to CHD after repeated administration. Patients were given 5 or 10 mg bisoprolol once daily for 2 weeks according to a double-blind, randomized cross-over design. At entry one exercise tolerance test (ETT) served as baseline measurement and following each treatment period ETTs were performed before (24-hour value) and 3 hours after tablet intake. Exercise capacity (in W X min) was calculated until the onset of angina, 0.1 mV ST-segment depression and at peak exercise. Compared to baseline all workload values during active therapy were significantly improved (P less than or equal to 0.05) except for the workload till onset of angina with bisoprolol 5 mg at 24 hours. The effects at 3 hours were significantly stronger than those after 24 hours for both dosages. Significantly stronger effects were observed 3 hours as well as 24 hours after intake during treatment with 10 mg compared to 5 mg: at peak exercise on heart rate (P less than or equal to 0.05) and exercise capacity (P less than or equal to 0.01), at identical workload on heart rate (P less than or equal to 0.01) and rate-pressure product (P less than or equal to 0.01). It was found that bisoprolol 5 mg once daily leads to therapeutic effects with a clearly maintained duration of action over 24 hours, but further increase of peak exercise capacity may be achieved with 10 mg.

Administration, Oral↗
PubMed1987

[Potential antiangiogenic substances from alpha,alpha'-bis(amidinobenzyl)cycloalkanone derivatives and alpha-(arylsulfonylamino)-omega-phenylcarboxylic acid-4-amidinoanilide].

Assuming that the immigration of endothelial cells from existing blood vessels into tissues to be vascularized is the first step of neoangiogenesis, we examined the potential antiangiogenic activity of some synthetic inhibitors of serine proteinases on the migratory rate of isolated endothelial cell using Boyden technique. The 4-amidinoanilide of 2-tosylamino-4-phenylbutyric acid was shown to be the most effective inhibitor. Its effect is probably caused by inhibition of the plasminogen activators of tissue type produced by the cells.

4-Aminobenzoic Acid↗
PubMed1987

[Synthetic inhibitors of serine proteinases. 32. Inhibition of trypsin, plasmin and thrombin by amides of N-alpha-substituted 4-amidinophenylalanine. Effect of various amino acids and blocking groups of the n-alpha residue on inhibitory activity].

Cyclic amides of N alpha-arylsulfonylated 4-amidinophenylalanine are specific, highly potent inhibitors of thrombin. Introduction of amino acids between the arylsulfonyl blocking group and amino nitrogen influence particularly the antithrombin activity. By the use of glycine as spacer the compounds become tight binding thrombin inhibitors, while introduction of other omega-amino acids, Gly-Gly, L-Pro, Gly-L-Pro or L-Pro-Gly, reduces the specificity and potency of thrombin inhibition. Substitution of the arylsulfonyl blocking group for a heteroarylsulfonyl residue or an aryl residue causes a decrease in antithrombin activity, while substitution for a benzoyloxycarbonyl blocking group has only slight influence. It is concluded that the N alpha-moiety is of decisive importance for the antithrombin activity of derivatives of 4-amidinophenylalanine.

Amidines↗
PubMed1987

Prostaglandins in the menstrual cycle of women. A review.

The changes of concentrations of prostaglandins (PG) are cyclic in the uterine tissues and related to steroid ovarian hormones. The role in normal menstruation is presumably related to a local haemodynamic effect. PGF2 alpha vasoconstricts the endometrial vessels during menstruation and contracts the smooth muscle of the myometrium. PGE2 vasodilates the vessels of the endometrium, and PGI2 relaxes smooth muscle, vasodilates the vessels of the myometrium and inhibits thrombocyte aggregation. The pathological conditions dysmenorrhea and menorrhagia relates to symptoms which seem to be exaggerations of normal activities, probably due to increased PG levels. Prostaglandin synthesis inhibitors (PGSI) in women have not been able to prevent ovulation, but animal experiments have shown that the bursting of the follicle demands prostaglandins. In vitro experiments with human tissue have shown that PG is necessary for the occurrence of dissociation of connective tissue around the apex. Luteolysis is due to PG in several species, but it has not been possible to find this direct effect of PG upon luteolysis in women. However, there are indications that the PG functions as a mediator for or is mediated by catecholamines and/or oxytocin.

Animals↗
PubMed1987

Transfer factor for adjuvant immunotherapy in cervical cancer.

In a prospective randomized double-blind study of 60 patients with invasive cervical cancer, 32 were treated with transfer factor (TF) derived from leukocytes of the patients' husbands, and 28 were treated with placebo. Within the first 2 years after radical hysterectomy, five out of 32 TF-treated patients and 11 out of 28 placebo-treated patients developed recurrence of malignancy. Excluding one further patient with intercurrent death this difference is significant (chi 2 = 3.9915; P less than 0.05). Subdividing the collectives, significant differences were found in patients aged below 35 years and in patients with stage I disease. Identical immune profiles were checked in leukocyte donors prior to leukophoresis and were serially checked in patients. Antigen-specific correlations were found between donors' and recipients' reactivities but not between donors' reactivity and recipient's course of the disease.

Clinical Trials as Topic↗
PubMed1987

Estimation of myocardial infarct size by electrocardiographic and radionuclide techniques.

The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Trial was a randomized, experimental, multicenter clinical study comparing intravenous streptokinase therapy to conventional therapy of acute myocardial infarction. Myocardial infarct size was estimated by spatial vectorcardiography in 93 patients in the treatment group and 80 patients in the control group eight weeks post MI. The estimated infarct size for the treated group was smaller: 16 +/- 10% MI vs. 20 +/- 9% MI for the control group, P = 0.01. Four independent techniques to estimate infarct size were prospectively compared within the same day: Cowan's spatial VCG; the Selvestor/Wagner QRS score; 99m technetium synchronized ejection fractions and 201-Thallium Tomography. There was strong correlation between the two ECG techniques (r = 0.88) and between the two radionuclide techniques (r = 0.77). Statistically significant correlations (P = 0.0001) were described, respectively, among the four techniques, but the correlations were not clinically strong between electrocardiographic and radionuclide techniques: IAD vs. EF, r = -0.41; IAD vs. 201-Tl, r = 0.50; QRS Score vs. EF, r = -0.49; QRS Score vs. 201-Tl, r = 0.58.

Clinical Trials as Topic↗