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Biomedical subjects

H Wild

Publications and source records attributed to H Wild.

At least 19 recordsLinked to original sources
PubMed2001

Discovery of heterocyclic ureas as a new class of raf kinase inhibitors: identification of a second generation lead by a combinatorial chemistry approach.

Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as novel inhibitors of raf kinase, a key mediator in the ras signal transduction pathway. Structure-activity relationships were established, and the potency of the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial synthesis approach enabled the identification of a breakthrough lead (IC(50)=0.54 microM) for a second generation series of heterocyclic urea raf kinase inhibitors.

Proto-Oncogene Proteins c-raf↗
PubMed2001

Making faces: creating three-dimensional parameterized models of facial expression.

Previous studies of the perceptual processing and dynamics of emotional expression in faces have been limited by the lack of realistic yet controlled stimuli. The present work offers researchers a method for creating such stimuli for exploring these phenomena. We describe the creation of the stimuli and a series of experiments testing the validity of these stimuli with respect to emotional expressions in humans. Participants evaluated synthesized facial images and standardized photographs of six basic emotional expressions for intensity and accuracy of perceived emotion. Comparisons of these measures were qualitatively similar for synthesized and photographed faces. A manipulation of the magnitude of the synthesized expressions yielded a significant effect on the perceived intensity of expression. In a subsequent multidimensional scaling study, no systematic differences were uncovered in the derived configurations of the synthesized expressions and the photographs. These results are discussed in the context of possible future research applications.

Emotions↗
PubMed1999

Ribosomal RNA is the target for oxazolidinones, a novel class of translational inhibitors.

Oxazolidinones are antibacterial agents that act primarily against gram-positive bacteria by inhibiting protein synthesis. The binding of oxazolidinones to 70S ribosomes from Escherichia coli was studied by both UV-induced cross-linking using an azido derivative of oxazolidinone and chemical footprinting using dimethyl sulphate. Oxazolidinone binding sites were found on both 30S and 50S subunits, rRNA being the only target. On 16S rRNA, an oxazolidinone footprint was found at A864 in the central domain. 23S rRNA residues involved in oxazolidinone binding were U2113, A2114, U2118, A2119, and C2153, all in domain V. This region is close to the binding site of protein L1 and of the 3' end of tRNA in the E site. The mechanism of action of oxazolidinones in vitro was examined in a purified translation system from E. coli using natural mRNA. The rate of elongation reaction of translation was decreased, most probably because of an inhibition of tRNA translocation, and the length of nascent peptide chains was strongly reduced. Both binding sites and mode of action of oxazolidinones are unique among the antibiotics known to act on the ribosome.

Anti-Bacterial Agents↗
PubMed1991

Mechanisms of fat-related modulation of N-nitrosodiethylamine-induced tumors in rats: organ distribution, blood lipids, enzymes and pro-oxidant state.

Groups of rats, either dosed with N-nitrosodiethylamine (NDEA) for 10 weeks (from the age of 7 to 17 weeks) or untreated, were fed diets containing either 2% (low fat, LF) or 30% polyunsaturated fat (high fat, HF) on an equicaloric basis from 5 weeks until rats were 43 weeks old. Biochemical parameters were measured during and at the end of the experiment in various organs, blood, urine and exhaled air, for correlation with the presence or absence of tumors. The HF diet tended to increase the number of hepatic tumors induced by NDEA, while the number of extrahepatic tumors was higher in rats fed on the LF diet; also the overall tumor incidence was higher in the LF group. In the HF/NDEA group, only two benign extrahepatic tumors were found. Plasma total and free cholesterol and triglyceride concentrations were lower in the HF than the LF group without NDEA treatment. In animals bearing liver and/or extrahepatic tumors all plasma lipid concentrations were lower than in tumor-free animals. Only minor or no changes were detected in blood catalase activity, malondialdehyde level, reduced glutathione (GSH) level or GSH-related enzymes and excretion of thioethers in the urine due to dietary modulation or NDEA. Changes in the liver that were associated with the HF diet were: (i) increased amounts of some polyunsaturated fatty acids and of total phospholipids in liver microsomes; (ii) an enhanced level of lipid peroxidation in liver; (iii) a decrease in liver glutathione levels during NDEA treatment, with a simultaneous adaptive increase in superoxide dismutase levels, and a decrease in renal glutathione levels in both treated and untreated groups; (iv) enhanced microsomal induction of aminopyrine N-demethylase and epoxide hydrolase activities by NDEA, and (v) decreased hexose monophosphate shunt (HMS) activity. All mono-oxygenase activities were lower, and the activities of epoxide hydrolase, UDP-glucuronosyltransferase and HMS were higher, in liver tumors than in non-tumorous liver of similarly-treated rats. Neither diet nor NDEA had a major effect on drug-metabolizing enzyme activities in lung and kidney. HF diet significantly increased ethane exhalation (an indicator of the whole-body pro-oxidant state) over those on the LF diet: in rats on either diet, it was further increased when NDEA was given. Ethane exhalation was still elevated 30 weeks after the cessation of NDEA treatment. Our results suggest an association between the observed changes in biochemical parameters, notably oxidative stress, due to dietary modulation and the altered tumor incidence and organ distribution of tumors induced by NDEA.

Alanine Transaminase↗
PubMed1990

An analysis of neural spike-train distributions: determinants of the response of visual cortex neurons to changes in orientation and spatial frequency.

A previously unexploited method of examining neural spike-trains was applied to data obtained from cells in the visual cortex. Distributions of interspike intervals recorded extracellularly from cat visual cortex under four conditions were analyzed. Stimuli were gratings differing in orientation and spatial frequency. The probability density function of first passage time for a random walk with drift process, which is defined by its barrier height and drift coefficient, was used to characterize the generating process of axonal discharge under resting and stimulus conditions. Drift coefficient and barrier height were derived from the sample mean and standard deviation of the measured inter-spike intervals. For cells with simple receptive fields, variations in the drift coefficient were produced by changes in orientation and spatial frequency. Variations in barrier height were produced only by changes in orientation of the stimulus.

Animals↗
PubMed1986

Nitrate and nitrite in normal gastric juice. Precursors of the endogenous N-nitroso compound synthesis.

The nitrate and nitrite levels of 75 gastric juice samples from young and healthy fasting volunteers were examined. For both parameters a dependence on the specific pH value of the secretion was detected. The rise of the nitrite level from normal 0.1 ppm in the acid to 1.4 ppm in the neutral range can be explained by the activity of the bacterial flora even in the healthy stomach, which has already been demonstrated earlier. The hitherto existing theory that nitrate originates exclusively from the salivary glands, and if not reduced to nitrite by bacteria in the mouth cavity, is brought into the stomach via swallowed saliva only, does not explain the observation that there is a rise in nitrate concentration in neutral juice, too. Further investigations have to be made to see whether there are other endogenous sources of nitrate except the salivary glands in the gastrointestinal tract. The environmental pollutant nitrate must be paid more attention to in future.

Adult↗
PubMed1979

[Intelligence findings in children and adolescents with congenital cataract].

In children and young people with congenital cataracts the verbal intelligence quotient gives higher values than the perceptive-practical IQ. Longitudinal studies show the IQv reduced, but not the IQH. Connections exist between visual acuity and the IQ value, and the causes can be assumed to be disturbances of verbal information processing.

Adolescent↗