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Biomedical subjects

G Wagner

Publications and source records attributed to G Wagner.

At least 469 records · Page 26Linked to original sources

[Evaluation of procedures for vaginal disinfection].

At the occasion of the usual preparations preceding gynecological operations the average vaginal bacterial release of 42 patients, already anaesthesized, was assessed by a rinsing technique to be 5,04 +/- 0,98 log10 c.f.u. per ml sampling fluid after aerobic and anaerobic culture. The reduction of this bacterial release caused by the measurement itself is relatively small, therefore the technique was found to be suitable for evaluation of the efficacy of germreducing measures like irrigation or disinfection. An irrigation with isotonic saline during 30 s was measured to reduce the vaginal bacterial release by 0,4 +/- 0,5 log-steps. A solution containing 0,08% chlorhexidine gluconate + 0,1% benzalkon gluconate applicated during 5 min caused a reduction of 1,04 +/- 0,76 and a watery solution of povidone-iodine one of 2,29 +/- 1,00 log-units when used for 3 min. When after disinfection the sustained antimicrobial action of the chlorhexidin-containing preparation was not neutralized already during the sampling process by Tween 80 + lecithine + histidine being contained in the sampling fluid, an erroneously optimistic log reduction of 2,35 +/- 0,48 was measured. From the results it was calculated that 17-23 volunteers are necessary in order to detect with sufficient statistical safety an observed mean log reduction to be 0,5 log-units smaller than a hypothetical minimal reduction of 2,00 log-steps as required provisionally on an arbitrary basis.

Aerobiosis↗

Human vaginal pH and sexual arousal.

The surface pH of the vagina was measured before and after sexual arousal by self-stimulation in ten healthy women. The mean value of six spots measured and pH measured in collected vaginal fluid was highly correlated. Two-way analysis of variance showed a mean increase of pH after orgasm (significant at the 0.5% level). The Wilcoxon matched-pairs test and a paired t-test showed a significant increase in three and four of the subjects, respectively, and a decrease in pH in one other subject. It is concluded that in the present laboratory setting, clitoral self-stimulation to orgasm only results in small changes of the vaginal surface pH.

Adult↗

[Synthesis of N-alpha-(arylsulfonylglycyl)amidinophenylalanine amides as highly active inhibitors of thrombin].

The headline compounds were prepared from purified cyanophenylalanines after presenting arylsulfonylglycyl residues, activation of the carboxyl group by formation of the p- nitrophenylester followed by aminolysis and transfer of a cyano in an amidine function. Besides some esters and an acid were synthetized with the basic structure mentioned in the headline . The p-compounds with a cycloaliphatic amide component proved as "tight binding inhibitors". The greatest antithrombin effect shows N alpha-(2- naphthylsulphonylglycyl )-4- amidinophenylalaninpiperidi d with a Ki-value of 6 X 10(-9) mol/l using S-2238 as a substrate.

Phenylalanine↗

Improved spectral resolution in cosy 1H NMR spectra of proteins via double quantum filtering.

A double quantum filter is inserted into a two-dimensional correlated (COSY) 1H NMR experiment to obtain phase-sensitive spectra in which both cross peak and diagonal peak multiplets have anti-phase fine structure, and in which the cross peaks and the major contribution to the diagonal peaks have absorption lineshapes in both dimensions. The elimination of the dispersive character of the diagonal peaks in phase-sensitive, double quantum-filtered COSY spectra allows identification of cross peaks lying immediately adjacent to the diagonal, which represents a significant improvement over the conventional COSY experiment.

Magnetic Resonance Spectroscopy↗

Protein conformation and proton nuclear-magnetic-resonance chemical shifts.

The nuclear magnetic resonance (NMR) chemical shifts of the polypeptide backbone protons in basic pancreatic trypsin inhibitor from bovine organs and the inhibitors E and K from the venom of Dendroaspis polylepis polylepis have been analyzed. Using the corresponding shifts in model peptides, the chemical shifts observed in the proteins were decomposed into random-coil shifts and conformation-dependent shifts. Correlations between contributions to the latter term and the polypeptide conformation were investigated by using the crystal structure of the bovine inhibitor. In addition to the well-known ring-current effects, a correlation was found between chemical shifts of amide and C alpha protons and the length of the hydrogen bonds formed by these protons with nearby oxygen atoms as acceptor groups. There remain sizeable and as yet unexplained residual conformation shifts. Overall, the present treatment provides a satisfactory qualitative explanation for the outstandingly large shifts of backbone hydrogen atoms in these diamagnetic proteins.

Amino Acid Sequence↗

[Transfer factor as adjuvant immunotherapy in invasive cervix cancer. Report of a double-blind study].

From 1977 to 1982 a prospective randomized double-blind study comparing transfer-factor (TF) versus placebo was conducted in invasive cervical cancer patients after radical surgery and irradiation. The husbands of the cancer patients were selected as leukocyte donors for TF preparations. 60 patients entered the study; 28 patients received placebo and 32 patients received TF. The comparability of both collectives was excellent concerning age and tumor stage. One patient treated with TF died intercurrently. The rate of recurrence of cancer was 5 in the 31 TF-treated patients and 11 in the 28 patients receiving placebo, which was significantly different (p less than 0,05). This difference was even greater when only patients treated for at least 3 months were compared (3 recurrences in the TF-group and 11 recurrences in the placebo-group). Further aspects of this clear clinical results are discussed.

Adult↗

[lst report: Alternatives to cortisone therapy. lst clinical experiences with a carnitine-betamethasone combination for the stimulation of fetal lung maturity].

In the recent past criticism has been voiced with regard to the efficacy and possible side effects of corticosteroid prophylaxis of fetal respiratory distress syndrome (RDS). Apparently the efficacy of this treatment has been over-estimated and the spectrum of possible side effects has not received enough critical attention. In view of the multiple indications that the fetal metabolism, above all, may be altered by this type of therapy, it seems necessary to search for other methods of surfactant stimulation. This paper presents the first clinical study on the use of carnitine (4 g for 5 days in combination with twice 8 mg beta-methasone versus twice 8 mg betamethasone alone). The patients on combination therapy showed a more marked increase in surfactant content of the amniotic fluid. Lung compliance determination in infants born within 72 hours of completion of therapy also revealed better results in the combination therapy group. There were also fewer clinically demonstrable RDS cases in this group. More research will be necessary to definitely establish the value of this new form of therapy.

Animals↗

Vasoactive intestinal polypeptide (VIP) as a putative neurotransmitter in penile erection.

The localization of vasoactive intestinal polypeptide (VIP) in the male genitourinary tract was investigated in the rabbit and man by means of radioimmunoassay and immunohistochemistry. In addition, the in vitro effect of VIP upon penile smooth muscle from man, the Vervet monkey, and the rabbit was investigated. Significant concentrations of VIP immunoreactivity were found in the human penis and all the organs of the rabbit genital tract apart from the testis. VIP immunoreactive nerve fibres were observed in the erectile tissue of the human and rabbit penis and in the other organs of the rabbit genital tract apart from the testis. Fibres were most abundant in association with blood vessels, in smooth muscle tissue, and subepithelially in glandular tissue. Strips of smooth muscle taken from the corpus cavernosum of Vervet monkey and man showed a dose-dependent relaxation in response to VIP at concentrations of 6 X 10(-8) mol X L-1 and 6 X 10(-7) mol X L-1. The data indicate that VIP may be an inhibitory neurotransmitter involved in the nervous control of penile erection.

Adult↗

Two-dimensional double quantum 1H NMR spectroscopy of proteins.

Two-dimensional double quantum 1H NMR spectra are recorded for a protein. The application of this technique to macromolecules is shown not to be impeded by the long preparation pulse sequence essential for this experiment. The identification of spin systems by analysis of the double quantum spectrum is illustrated. Since double quantum spectra do not contain diagonal peaks, connectivities between almost degenerate signals can be detected. By analysis of remote connectivities (i) it can be established whether amide and beta-protons belong to the same spin system or not, (ii) degeneracy of beta-proton chemical shifts can be demonstrated, and (iii) glycine amide protons can be distinguished from all others.

Amides↗

Cyclic amides of N alpha-arylsulfonylaminoacylated 4-amidinophenylalanine--tight binding inhibitors of thrombin.

Variation of the potent thrombin inhibitors derived from N alpha-arylsulfonyl-4-amidinophenylalanine was carried out by interposition of an omega-aminoalkylcarboxylic acid between the N alpha-arylsulfonyl residue and the 4-amidinophenylalanine part. The use of glycine as spacer renders the compounds tight binding inhibitors of thrombin. The Ki of the most potent inhibitor reaches the nmol/l range. The inhibitory effect is specifically directed against thrombin, the Ki values for inhibition of trypsin, plasmin and factor Xa are some orders of magnitude higher than those for thrombin inhibition.

Animals↗

[Dynamics of protein structures].

This review presents a survey of experimental and theoretical methods capable of providing a many-parameter characterization of internal mobility of protein molecules. Special emphasis is on applications of high-resolution nuclear magnetic resonance for studies of non-crystalline proteins and discussions of possible correlations between protein dynamics and biological functions of proteins.

Amino Acid Sequence↗

Peyronie's disease and erectile failure.

A total of 20 patients with Peyronie's disease, including 15 with erectile failure and 5 with normal potency, underwent evaluation with dynamic xenon washout and infusion cavernosography. Abnormal drainage from the cavernous body was found in 13 of the 15 patients with erectile failure and in none of the 5 potent patients (p less than 0.01), indicating that this condition seems to be the underlying pathological mechanism leading to erectile impotence in patients with Peyronie's disease.

Adult↗

Characterization of the distribution of internal motions in the basic pancreatic trypsin inhibitor using a large number of internal NMR probes.

The experimental observations described in this article indicated that a distribution of many different fluctuations is present in a globular protein. These fluctuations were characterized by observation of many natural internal probes such as the labile peptide protons and the aromatic side chains. The conditions which are necessary to get reactions of the internal probes have been discussed in detail. The structural interpretation of the data was facilitated by the development and the use of new NMR techniques which provided the identification of the resonances of all the labile peptide protons. With NOE measurements a distinction between correlated and uncorrelated exchange events was obtained. This enabled us to elucidate the exchange mechanism over a wide range of p2H and temperature and to classify different subsets of fluctuations with respect to their lifetimes. It was further demonstrated that a change of external conditions such as temperature, p2H or pressure can change the distribution of fluctuations in the protein. The mechanisms responsible for rotation of internal aromatic side chains were also found to change with temperature, and mechanistic aspects of these fluctuations were discussed. This demonstration of a manifold of spatial fluctuations in a small protein provides an impression on the kind of fluctuations which have to be expected for larger proteins. When studying protein reactions one should therefore consider the presence of a large number of different, transiently formed, spatial structures available for the partner in the reaction, which may pick out only that structure which will optimally perform a particular reaction with the highest efficiency.

Magnetic Resonance Spectroscopy↗

[Medical history of invasive cervical carcinoma. Symptoms and medical care in 87 cases].

The history of 87 patients suffering from invasive cervical cancer was taken using a special pattern of questions at the time of the patient's clinical admittance. After a minimum of two years after therapy the course of the disease was evaluated in each case and compared to the history and the stage of the tumor. The symptoms "postcoital bleeding" and "metrorrhagia" were found in different frequency in a significant dependence of the stage of the tumor. 26 patients (30%) had undergone a gynecologic examination without suspicion of malignancy within two years before clinical admittance, 18 of them in combination with a routine "PAP-smear". 15 patients reported the last unsuspicious examination even within the last year before clinical admittance. In this group of patients the highest rates of pelvic lymph node involvement (33,3%) and of mortality from recurrence (26,7%) were found. This surprising fact can be seen as evidence for a second form of cervical cancer with rapid invasive growth which may apart from false negative cytologic results be responsible for apparent failures of preventive care.

Adult↗