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Biomedical subjects

M Wolters

Publications and source records attributed to M Wolters.

At least 37 records · Page 2Linked to original sources

Cognitive outcome after unilateral pallidal stimulation in Parkinson's disease.

OBJECTIVES: Chronic high frequency electrostimulation of the globus pallidus internus mimics pallidotomy and improves clinical symptoms in Parkinson's disease. The aim of this study was to investigate the cognitive consequences of unilateral deep brain stimulation. METHODS: Twenty non-demented patients with Parkinson's disease (age range 38-70 years) were neuropsychologically assessed 2 months before and 3 months after unilateral pallidal stimulation. The cognitive assessment included measures of memory, spatial behaviour, and executive and psychomotor function. In addition to group analysis of cognitive change, a cognitive impairment index (CII) was calculated for each individual patient representing the percentage of cognitive measures that fell more than 1 SD below the mean of a corresponding normative sample. RESULTS: Neurological assessment with the Hoehn and Yahr scale and the unified Parkinson's disease rating scale disclosed a significant postoperative reduction in average clinical Parkinson's disease symptomatology (p<0.001). Repeated measures multivariate analysis of variance (using right/left side of stimulation as a between subjects factor) showed no significant postoperative change in cognitive performance for the total patient group (main effect of operation). The side of stimulation did not show a significant differential effect on cognitive performance (main effect of lateralisation). There was no significant operation by lateralisation interaction effect. Although the patients experienced significant motor symptom relief after pallidal stimulation, they remained mildly depressed after surgery. Analysis of the individual CII changes showed a postoperative cognitive decline in 30% of the patients. These patients were significantly older and took higher preoperative doses of levodopa than patients showing no change or a postoperative cognitive improvement. CONCLUSIONS: Left or right pallidal stimulation for the relief of motor symptoms in Parkinson's disease seems relatively safe, although older patients and patients needing high preoperative doses of levodopa seem to be more vulnerable for cognitive decline after deep brain stimulation.

Adult↗

Bacillus stearothermophilus lctB gene gives rise to functional K+ channels in Escherichia coli and in Xenopus oocytes.

We have cloned a small K+ channel subunit (LctB) of the gram-positive bacterium Bacillus stearothermophilus (B. stearo.). The B. stearo. LctB protein is only 134 amino acids long. The sequence contains a typical K+ channel P-domain with a K+ channel GYGD signature sequence and two hydrophobic, possibly membrane-spanning segments M1 and M2. Unexpectedly, LctB K+ channels exhibited properties which differed markedly from the ones reported for KcsA channels of the gram-positive bacterium Streptomyces lividans. LctB channels, when expressed in E. coli, were targeted to the outer membrane and not like KcsA channels to the inner membrane. After reconstitution in black lipid membrane, LctB channels mediated K+ currents at neutral pH. They were apparently not gated by pH like KcsA channels. Also, LctB cRNA produced functional LctB channels in the Xenopus oocyte expression system in marked contrast to KcsA. The results demonstrated that heterologous expression produced functional LctB channels both in E. coli and in Xenopus oocytes. It is proposed that bacterial LctB subunits can be properly handled by the Xenopus oocyte leading to the occurrence of functional LctB K+ channels in the oocyte plasma membrane.

Amino Acid Sequence↗

Secondary structure, stability and tetramerisation of recombinant K(V)1.1 potassium channel cytoplasmic N-terminal fragment.

The recombinant N-terminal fragment (amino acids 14-162) of a tetrameric voltage-gated potassium channel (K(V)1.1) has been studied using spectroscopic techniques. Evidence is presented that it forms a tetramer in aqueous solution, whereas when solubilised in 1% Triton X-100 it remains monomeric. The secondary structure content of both monomeric and tetrameric K(V)1.1 N-terminal fragment has been estimated from FTIR and CD spectroscopy to be 20-25% alpha-helix, 20-25% beta-sheet, 20% turns and 30-40% random coil. Solubilisation of the protein in detergent is shown by hydrogen-deuterium exchange analysis to alter tertiary structure rather than secondary structure and this may be the determining factor in tetramerisation ability. Using molecular modelling we propose a supersecondary structure consisting of two structural domains.

Amino Acid Sequence↗

A highly efficient 24-condition matrix for the crystallization of nucleic acid fragments.

A matrix screen is presented with optimized conditions for the crystallization of nucleic acid fragments. The screen consists of 24 conditions only and utilizes minimal amounts of sample. It has been tested on a series of DNA and RNA oligomers, and yielded diffraction-quality crystals of many specimens including drug-DNA complexes. Preliminary X-ray analysis of the crystals is reported.

Chemistry Techniques, Analytical↗

[Computer-assisted analysis of urethral pressure profiles in the woman].

The regular urethral stress profile which is applied for the diagnosis in urinary stress incontinence has been modified in two respects: Volley-like increasing pressure and a final spline-interpolation. With this method it is possible to analyze virtual standards for any variable of the profile. Measurements were carried out in 20 stress incontinent female patients compared with 10 healthy women. Urinary stress incontinence could not be verified through regular profiles (i.e. methods) in each of the 20 impaired patients. After the stress profile had been modified we proved that 11 Aases auf twenty definitely suffered from urethral insufficiency, 6 patients showed a deterioration of the profile and 3 had no change. It is possible to prove urinary stress incontinence by tracing the dynamics of the urethral pressure response which shows an irregular pattern in incontinent women.

Adult↗

Analysis of c-erbB2 protein content of human glioma cells and tumor tissue.

This study was designed to determine whether or not overexpression of the c-erbB2 protein plays a role in the etiology of human gliomas. The c-erbB2 gene codes for a 185 kDa cell membrane glycoprotein (gp185c-erbB2), which is similar to the receptor for epidermal growth factor. In initial studies, four human glioma cell lines (A-172, U118MG, U138MG and SW608) were used to develop techniques for detecting and quantifying gp185c-erbB2, using immunofluorescence microscopy, immunoblot analysis and flow cytometry. A-172 cells were found to have the highest content of gp185c-erbB2. More detailed studies utilizing A-172 cells indicated that cellular gp185c-erbB2 content changed little in response to conditions affecting cellular proliferative status, including serum deprivation, growth in low glucose medium and treatment with dimethyl sulfoxide. Ten human glioma specimens were then analyzed for cellular gp185c-erbB2 fluorescence and DNA content, using A-172 cells as a biological standard. Results indicated that gp185c-erbB2 was expressed at levels comparable to that of A-172 cells in many specimens, and at a very high level in one specimen. These data reiterate the problem of the molecular heterogeneity of human gliomas and indicate that gp185c-erbB2 may have a role in at least a subset of malignant glial tumors.

Brain Neoplasms↗

Forgiving heart.

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Humans↗

[A three-year aid program for plastic surgery in Peshawar (Pakistan). Ongoing management of severely injured patients of the Afghanistan war: 1,528 large operations, 5,171 smaller interventions, 15,932 patients examined].

Since 1980 Interplast Germany has sent many plastic surgeons to developing countries. In 1989 a new Interplast Germany program for helping Afghan refugees in Pakistan's Peshawar was started. The Federal Republic of Germany financed the first two years; thereafter, the European Community and Help supported the project. Twenty-four teams with 123 nurses, surgeons and anesthesiologists operated on 1,528 patients in two hospitals. In the same period 5,171 smaller operations have been performed and 15,932 patients have been examined. Low expense for the teams, good support by officials, and professional administration have made this project highly effective for 3 years.

Adult↗

A strategy for the construction of double-stranded DNA microcircles with circumferences less than 50 bp.

A procedure for the construction of double-stranded DNA microcircles is described that overcomes the natural limits of established circularization procedures. The assembly strategy needs only three components, i.e. two synthetic oligonucleotides containing any sequence of interest and T4 DNA ligase. All components can be provided in large quantities and only two enzymatic reaction steps are required. Such microcircles can serve as a model for topologically fixed and highly bent DNA molecules and the amounts needed for X-ray crystallography, n.m.r. spectroscopy or drug binding studies can readily be produced. The construction of a 42 base pair double-stranded DNA microcircle is presented, by far the smallest double-stranded DNA circle yet described either in vivo or in vitro.

Alkaline Phosphatase↗

Construction of a 42 base pair double stranded DNA microcircle.

A procedure for the construction of double stranded DNA microcircles is described that overcomes the natural limits of established circularization procedures. Starting with two synthetic oligonucleotides which are able to form dumbbell shaped structures, two subsequent ligation reactions yield a microcircle of double stranded DNA of 42 base pairs. This is by far the smallest circle of double stranded DNA yet described. These microcircles can be constructed in quantities required for high resolution structural analyses such as X-ray crystallography and NMR spectroscopy.

Base Composition↗

Observation on drug resistance of Trypanosoma (Nannomonas) congolense and Trypanosoma (Duttonella) vivax in cattle at a feedlot in the Northern Ivory Coast.

Studies carried out on feedlot cattle show Berenil at 7 mg/kg to be the treatment of choice in trypanosomiasis although repeated doses may be necessary. Resistant strains of Trypanosoma (Duttonella) vivax and Trypanosomas (Nannomonas) congolense survived dosages of between 0.5 mg/kg and 1.0 mg/kg of Trypamidium and were cross resistant to Homidium bromide.

Animals↗

Proteolytic fragmentation of Helix pomatia alpha-hemocyanin: structural domains in the polypeptide chain.

alpha-Hemocyanin from the Roman snail Helix pomatia is composed of polypeptide chains with a molecular weight of 360000 +/- 30000. The cylindrically shaped hemocyanin molecule contains 20 of these large chains. The polypeptide chain has been split into components with molecular weights of: 210000, 154000, 147000, 112000, 120000, 98000, 55000, and 50000, by gentle proteolysis with enzymes of different specificities. Most of the fragments have molecular weights which are about 50000 or a multiple of 50000. Departure from these values, as found in the 112000 and 120000 fragments, is probably caused by the high carbohydrates content of these components. A mixture of these fragments has the same oxygen binding properties as the nondigested protein. Subtilisin converts the hemocyanin polypeptide chain, under appropriate conditions, almost completely into fragments of 50000 and 55000 daltons with conservation of the oxygen binding properties of the nondigested protein. We conclude from these studies that the polypeptide chain of Helix pomatia alpha-hemocyanin is folded into about seven compact tertiary structures, which are covalently interconnected. This chain of structural domains has been visualized. (Siezen and Van Bruggen (1974), J. Mol. Biol. 90, 77-89) by electron microscopy, which shows 1/20 hemocyanin molecules to be flexible structures consisting of 7-8 apparently spherical units of 55-60 A diameter.

Animals↗