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Biomedical subjects

W Werner

Publications and source records attributed to W Werner.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Fetal plexus cysts. An indication for prenatal karyotyping].

From March 1988 to September 1990, 1844 patients (pregnant women) were sonographically examined following a pregnancy monitoring programme and for further diagnostic clarification of unclear sonographic patterns. The ultrasound examinations were carried out with a 3.5 Mhz convex transducer, and by pregnancies before the 16th week with a 5 Mhz vaginal transducer (Toshiba SSA 250 a), respectively. In 13 cases (0.7%), foetal chorioidal plexus cysts were found; in 6 of them they occurred unilaterally and in the other 7 bilaterally. In general, most of the cases were diagnosed between the 13th and 22nd weeks of pregnancy. All unilateral cysts appeared transitorily, were of small size and receded by the 24th week of pregnancy. From the 7 patients with bilateral plexus cysts, 4 foetuses showed no signs of anatomical abnormalities. In the other 3 foetuses, it was possible, to recognise further anatomical abnormalities, when performing ultrasound i.e. 2 of them proved to be a trisomy 18 and the third case a trisomy 21.

Abnormalities, Multiple↗
PubMed1991

Static firing rates of premotor and primary motor cortical neurons associated with torque and joint position.

Single cell activity was studied in the postarcuate premotor area (PMA) and primary motor cortex (MI) of two monkeys performing a load-bearing task with the contralateral hand. Steady-state discharge rates were examined in relation to positional maintenance of the wrist which was held in one of three given positions against graded torques directed towards flexion or extension. Significant and monotonic relationships between tonic firing rate and static torque were found in 41% of 477 MI cells and in only 26% of 470 units studied in PMA. However, for specific cell groups in the PMA the proportion of load-related neurons reached that of the MI samples; this was true for pyramidal tract neurons (PTNs) and for 'non-PTNs' if recorded in their vicinity. The most interesting difference pertains to the range of load over which cells in both areas modulated activity. MI neurons showed steepest change of firing rates over a limited range of small torques around zero external load; the population average displayed a sigmoidal relationship. Proportionally more PMA neurons increased their activity over the entire range of torques examined or showed the highest increase with stronger torques; the population average best fitted a quadratic function. The mean firing rate-torque slope of the PMA population was significantly smaller than that of MI. Many cells in either area were related to both torque and joint position and displayed correlates of length-tension properties of muscle. Change of position sensitivity with torque was found to parallel the rate-torque characteristics in individual neurons. Mean position sensitivity of PMA neurons increased with increasing torques in the 'preferred' direction. In contrast, greatest position sensitivity of the MI population occurred over the range of low torques, which means a clear quantitative dissociation from the muscular activities. The results suggest differential roles of MI and PMA in the control of 'fine' versus 'gross' muscular forces. Undoubtedly, some PMA cell elements (possibly certain output neurons) are involved in aspects of postural control of EMG adjustment to load and joint position.

Animals↗
PubMed1991

Phasic and tonic responses of premotor and primary motor cortex neurons to torque changes.

Responses to torque step perturbation of the wrist were compared in premotor area (PMA) and motor cortex (MI) neurons of the monkey. A substantial portion (39%) of cells recorded from the PMA had phasic responses with onset latencies as short as those found in MI (mostly between 15 and 50 ms). Responsiveness to small perturbations, directional specificity and linear correlation of phasic responses with the velocity of displacement are properties that were essentially present in the PMA. A role of somatosensory feedback to the PMA in accurate and fast up-dating of movement is suggested. Tonically sustained responses to torque change (mean latency around 60 ms) were encountered in both areas and preferentially in neurons that had a monotonic load-relationship under steady-state condition. Such cortical responses did not exhibit reflex-like features, i.e. no correlation with amplitude of torque step and resulting displacement. Instead, the new load condition seemed to be represented by the tonic response of any particular neuron in accordance with its individual firing rate-load characteristics. These tonic cortical responses may be involved in the swift and effective adaptation to the actual load.

Animals↗
PubMed1991

[Saponins from Thinouia coriacea].

The investigation of the stems of Thinouia coriacea Britton (Sapindaceae), an ichthyotoxic plant from South Brazil, afforded eight glycosides of oleanolic acid. Structures were assigned based on data from partial hydrolysis. 13C-NMR and mass spectral procedures as 3-O-alpha-L-arabinopyranoside (1), 3-O-alpha-L-rhamnopyranosyl-(1----2)-alpha-L-arabinopyranoside+ ++ (2), 3-O-beta-D-glucopyranosyl-(1----4)-alpha-L-arabinopyranoside (3), 3-O-beta-D-glucopyranosyl-(1----3)-alpha-L-rhamnopyranosyl-(1----2 )-alpha-L-arabinopyranoside (4), 3-O-alpha-L-rhamnopyranosyl-(1----2)[beta-D-glucopyranosyl-(1----4 )]-alpha-L-arabinopyranoside (5), 3-O-beta-D-xylopyranosyl-(1----3)-alpha-L-rhamnopyranosyl-(1----2) [beta-D-glucopyranosyl-(1----4)[alpha-L-arabinopyranoside (6), 3-O-beta-D-glucopyranosyl-(1----3)-alpha-L-rhamnopyranosyl-(1----2 )[beta-D-glucopyranosyl-(1----4)]-alpha-L-arabinopyranoside (8). Saponin 7 showed the same sugars as 8, but the attachment between the sugars could not be elucidated. The same saponins were present in the roots, but not in the leaves.

Carbohydrate Sequence↗
PubMed1991

Bestatin-induced enhancement of in vivo phagocytosis determined by a new simple assay.

Pretreatment of mice by the immunostimulator bestatin resulted after four days in a significant enhancement of the phagocytic activity of peritoneal cells. For quantification of the phagocytic process of murine peritoneal phagocytes a new in vivo assay is proposed. Fluorescein isothiocyanate (FITC)-labeled Escherichia coli bacteria were i.p. injected. After ten minutes peritoneal cells were harvested and the phagocytic index of peritoneal phagocytes was fluorescence-photometrically assessed. The frequency distribution of phagocytized bacteria per cell found by the this assay corresponded to Poisson distribution. This coincidence allowed estimation of the minimum number of cells needed for detecting a significant difference of phagocytosis indices, resulting in an enhancement of test efficiency.

Adjuvants, Immunologic↗
PubMed1991

[Synthesis of a potential metabolite of the carcinostatic bendamustin (Cytostasen)].

The synthesis of the methylester of (5-[Bis(2-chlorethyl)amino]-1-methyl-benzimidazolyl-(2))ethanolic acid (4) has been described. The assumption that the butanoic acid group of the anticancer drug bendamustine (Cytostasan) will be biotransformed in patients to the ethanoic acid group as found for chlorambucil has been disproved by means of a comparison of the methylated metabolites and 4 by MS and HPLC.

Antineoplastic Agents↗
PubMed1990

Physiochemical characterization of substituted chromeno[4,3-b][1,5]benzodiazepine stereoisomers designed as cell membrane active antitumor agents.

As an alternative to naturally occurring pyrrolo[2,1-c][1,4]benzodiazepines (e.g., antramycin) which possess properties of DNA alkylation, we have designed several antileukemic chromeno[4,3-b][1,5]benzodiazepine derivatives with potential activity toward leukemia cell membranes and the cyclic nucleotide system. The cis and trans diastereoisomers were characterized by NMR. The absolute configurations of the enantiomers were established by X-ray diffraction and circular dichroism (CD) measurements. By means of absorption spectroscopy and determinations of fluorescence and fluorescence decay, it was found that the cancerostatically active compound (+)(6aR, 13aS)-3,4-dimethoxy-10,11-dimethyl-6,6a,7,8,13, 13a-hexahydrochromeno[4,3-b][1,5]benzodiazepine (ZIMET 54/79) and its biologically inactive (-) enantiomer (ZIMET 55/79) interact with liposomal membranes. At pH values of 6.0 and 7.3 the long-wave absorption bands of these agents showed weak bathochromic and hypochromic effects upon addition of neutral, and positively and negatively charged phosphatidylcholine and phosphatidylcholine/cholesterol liposomes. Such spectral changes are interpreted as resulting from the binding of both agents to phospholipid bilayers. Steady-state determinations using the membrane probe 1-anilino-8-naphthalenesulfonic acid (1,8-ANS) led to the observation of a small decrease in fluorescence intensity in the presence of either agent. Time-resolved measurements demonstrate that the mechanism of action of the agents occurs mainly through the partial displacement of probe molecules from regions of hydrophobic binding to areas of greater solvent accessibility. No significant differences in binding between the cancerostatically active and inactive enantiomers with liposomes (archiral systems) were detectable on the basis of spectrophotometric and fluorescence determinations. Cell membrane bound adenylate cyclase is stimulated by ZIMET 54/79, resulting in an increase of 103% in the level of cAMP in mouse L1210 leukemia cells. On examination of structure-activity relationships, it was found that the biological activity (leukemia L1210, P388, Lewis lung carcinoma, melanoma B16, increase in cAMP) is correlated with the particular configuration (6aR,13aS) and type of substituent at positions 3 and 4 of the benzo ring in the case of alkoxy groups and positions 10 and 11 for methyl groups. No activity was detected toward DNA/RNA using microbial test systems.

Animals↗
PubMed1990

Expression of fowl adenovirus type 10 antigens in Escherichia coli.

In an attempt to construct a genetic map of the fowl adenovirus (FAV) and to determine which viral proteins are natural immunogens in chickens and hence may be relevant to protective immunity we have constructed an expression library of FAV type 10 DNA. The genomic DNA was partially digested with the restriction endonuclease Sau3A, and this DNA was inserted into the 3' terminal end of the beta-galactosidase gene in a plasmid vector. To date, approximately 600 clones have been identified that express FAV type 10 antigens as determined by immunological screening with rabbit antisera to purified virus, including one that has amino acid homology with the 100 kDa protein of human adenovirus type 5. These antigen positive clones were found to contain DNA from FAV type 10 genome as determined by hybridisation to FAV DNA. These clones will allow the further characterisation of FAV and possibly the identification of potential vaccine molecules.

Animals↗
PubMed1990

Pharmacodynamic study of F(ab')2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris.

The pharmacodynamics of intravenous bolus injections of 0.05, 0.10, 0.15, and 0.20 mg/kg of F(ab')2 fragments of the murine monoclonal antibody 7E3, 7E3-F(ab')2, directed against the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor of human platelets, were studied in groups of four patients with unstable angina pectoris. With 0.20 mg/kg, the template bleeding time prolonged from 6.3 +/- 1.9 (mean +/- SD) to greater than 30 min; it subsequently decreased to 13 +/- 7.8 min after 12 h and to 8.3 +/- 1.5 min after 24 h. The number of unblocked GPIIb/IIIa receptors (preinfusion value, 32,000 +/- 3,000 per platelet) decreased to 13 +/- 7% of the preinfusion value 1 h after infusion, and then increased to 33 +/- 10% at 12 h, 44 +/- 8% at 24 h and 67 +/- 7% at 72 h. The logarithm of the bleeding time was inversely proportional with the residual GPIIb/IIIa receptors (r = 0.73, P less than 0.0001). ADP-induced platelet aggregation (measured by changes in light transmittance in percent) decreased from 60 +/- 5% before infusion to 1.5 +/- 3% 1 h after infusion; it then increased to 29 +/- 3% after 24 h and 39 +/- 6% after 72 h. Platelet counts decreased by 16% at 1 h and returned to control values within 24 h. Proportionally smaller effects were seen at lower doses of 7E3-F(ab')2. Antibody injection did not induce spontaneous bleeding. Angina was not observed during the first 12 h when the bleeding time was significantly prolonged, but occurred in 6 of the 16 patients within the next 3 d. 2 of the 16 patients developed low titers of IgG antibodies specific for 7E3-F(ab')2. Thus 7E3-F(ab')2 induces dose-related inhibition of platelet function; at a dose of 0.20 mg/kg, it causes profound inhibition of platelet aggregation and prolongation of the bleeding time, but no spontaneous bleeding.

Adult↗
PubMed1989

Correlation between template bleeding times and spontaneous bleeding during treatment of acute myocardial infarction with recombinant tissue-type plasminogen activator.

The purpose of this study was to correlate bleeding complications during and after treatment with recombinant tissue-type plasminogen activator (rt-PA) with serial template bleeding time measurements, with ADP-induced platelet aggregation, with clinical characteristics, and with hemostatic parameters. Fifty-two of 55 consecutive patients with acute myocardial infarction and template bleeding times (Ivy method) of less than 9.5 minutes were treated with rt-PA in a total dose of 55-212 mg (mean, 109 mg) over 90 to 360 minutes (median, 240 minutes) combined with heparin. The mean bleeding time was significantly prolonged at 90 minutes (from 5.0 +/- 1.9 to 8.2 +/- 4.3 minutes, p less than 0.0001) but returned toward baseline after 4 hours (from a median of 8.0 to 7.0 minutes, p less than 0.05). Thirteen patients (25%) suffered relatively minor but spontaneous bleeding that did not correlate with age, hypertension, smoking, partial thromboplastin time, platelet count, ADP-induced platelet aggregation, steady-state rt-PA level, or extent of fibrinogen degradation. In multivariate analysis, only the 90-minute bleeding time correlated with spontaneous bleeding (p = 0.01). Prolongation of the 90-minute bleeding time to greater than or equal to 9 minutes, which occurred in 21 patients, correlated with spontaneous bleeding with a sensitivity of 69% (95% confidence interval, 39-90%) and a specificity of 69% (95% confidence interval, 52-83%). Retrospective analysis revealed that in 14 patients taking aspirin, the bleeding time at 90 minutes was significantly more prolonged (p less than 0.05) and spontaneous bleeding significantly more frequent (p less than 0.01) than in patients not taking aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

[Mitoguazone (methylglyoxal bis(guanylhydrazone))--its status and prospects].

Because of its severe side effects, initial clinical trials of the antineoplastic compound mitoguazone (Methyl-GAG, M-G) were ceased in the middle of 1960s. One decade later pharmacokinetically guided dose schedules as well as new experimental data on the antiproliferative mechanism of action stimulated new clinical studies. First results indicated that M-G had single-agent activity against various tumors such as acute leukemia and malignant lymphoma connected with acceptable tolerance. M-G seems to be effective especially in combination with other antineoplastic drugs. Its final evaluation may be reserved to further randomized trials. Recently, the psoriasis vulgaris is expected to be an additional field of the application of M-G. In this minireview data on synthesis, preclinical pharmacology, pharmacokinetics, biochemical effects and toxicology of M-G are given. Furthermore, clinical findings on M-G concerning its pharmacokinetic behaviour, antitumor and antipsoriatic activities are described.

Animals↗
PubMed1988

[HLA typing in Ullrich-Turner syndrome].

33 female patients with established anomaly of gonosomes were examined for the problem of a possible connection of the disease with certain types of HLA. An accumulation of individual specificites of HLA cannot be proved summarizingly; there are no significant differences to the control group. Remarkable and at present not yet to be interpreted is, however, the exclusive occurrence of the HLA-A1 in the 45,X-karyotype and iso-X-chromosomes, which needs further investigations.

Female↗
PubMed1988

Inherited deletion of subband Xp21.13 in a male with Duchenne muscular dystrophy.

The chromosomes of a male patient who suffers from Duchenne muscular dystrophy (DMD) with a molecular deletion were examined with an improved high resolution R type replication banding technique. High resolution cytogenetic analysis of the proband revealed a deletion of the Xp21.13 subband. His healthy mother was heterozygous for the deletion, which is subject to random X inactivation in lymphocytes. The X chromosomes of the proband's grandmother were normal, suggesting that the deletion of the Xp21.13 subband in the mother was a new mutation. The finding of a very small, cytologically visible Xp21.1 deletion in a male DMD patient with a molecular deletion emphasises the importance of resolving the fine structure in the Xp21 region.

Child↗
PubMed1988

Prevention of coronary artery reocclusion and reduction in late coronary artery stenosis after thrombolytic therapy in patients with acute myocardial infarction. A randomized study of maintenance infusion of recombinant human tissue-type plasminogen activator.

Sixty-eight patients with acute "transmural" myocardial infarction presenting within 6 hours (range, 1.3-5.8 hours) of onset of chest pain were given intravenous recombinant tissue-type plasminogen activator (rt-PA) at a dosage of 1 mg/kg during 90 minutes. Coronary angiography at 90 minutes revealed a patent infarct-related coronary artery in 52 patients (76%). These patients were randomized either to treatment by continuous infusion of heparin alone (27 patients) or to treatment by heparin and a maintenance infusion of rt-PA at a dosage of 0.8 mg/kg during 4 hours (25 patients). Coronary angiography was repeated 60 minutes after the start of the maintenance infusion and again after 8-14 days. Acute symptomatic reocclusion of the infarct-related artery occurred during the 1-hour observation period in five (19%) patients treated with heparin alone but in none of the patients treated with rt-PA (p = 0.05). The measured residual stenosis of the patent infarct-related coronary artery was similar in the heparin-treated and the rt-PA-treated groups at 90 minutes infusion: 66 +/- 14% versus 68 +/- 13% diameter stenosis, respectively (mean +/- SD) and 1.1 +/- 1.1 mm2 versus 0.82 +/- 0.7 mm2 area (p = 0.35). At 8-14 days after infusion, residual stenosis was unchanged in the heparin-treated group, but it improved to 55 +/- 17% (p = 0.001) and 1.6 +/- 1.2 mm2 (p = 0.003) in the rt-PA-treated group. At 90 minutes of infusion, residual intraluminal thrombus was observed in 29 of the 52 patients (56%) with a comparably measured distribution in the two groups (p = 0.43). At 150 minutes, however, the extent of intraluminal thrombus was significantly reduced in the rt-PA-treated group as compared with the heparin-treated group (p = 0.03). In-hospital ischemic events (symptomatic reocclusion, unstable angina, or cardiovascular death) occurred in 12 patients of the heparin-treated group but only in three patients of the rt-PA-treated group (p = 0.03). Fibrinogen levels decreased to 65 +/- 21% of baseline at 90 minutes of rt-PA infusion. During the rt-PA maintenance infusion, fibrinogen fell slightly from 63 +/- 26 to 57 +/- 28% (p = 0.18). This study shows that after successful reperfusion with 1 mg/kg rt-PA during 90 minutes, a maintenance infusion of 0.8 mg/kg rt-PA during 4 hours prevents acute symptomatic coronary artery reocclusion, and it reduces the frequency of ischemic events and the severity of residual coronary artery stenosis at hospital discharge.

Aged↗