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Biomedical subjects

S Winter

Publications and source records attributed to S Winter.

At least 73 records · Page 4Linked to original sources
PubMed1997

Conformational transitions provoked by organic solvents in beta-lactoglobulin: can a molten globule like intermediate be induced by the decrease in dielectric constant?

BACKGROUND: It is known that nonnative states of protein molecules can exist in living cells and can be involved in a number of physiological processes. It has also been established that the membrane surface can be responsible for the partial denaturation of proteins due to negative charges on it. The local decrease in the effective dielectric constant of water near the organic surface has been suggested to be an additional driving force for protein denaturation in the membrane field, but data to confirm this suggestion were lacking. RESULTS: Conformational transitions induced in beta-lactoglobulin by methanol, ethanol, isopropanol, dimethylformamide and dioxane were studied by near and far UV circular dichroism, steady-state tryptophan fluorescence and fluorescence decay of 8-anilinonaphthalene-1-sulfonate (8-ANS). The existence of at least two noncoinciding cooperative transitions has been established in all solvent systems studied. The first of these transitions describes the disruption of rigid tertiary structure in protein molecules, while the second reflects the formation of an expanded helical conformation typical of proteins in concentrated organic solvents. This means that the organic solvents provoke the formation of a denatured intermediate state with pronounced secondary structure and native-like compactness. We show that the positions of maxima in fI versus dielectric constant dependence virtually coincide for all five solvent systems studied. CONCLUSIONS: The decrease in the dielectric constant of the solvent induces in beta-lactoglobulin an equilibrium intermediate state. This state, being denatured, is relatively compact and has pronounced secondary structure and high affinity for the hydrophobic fluorescent probe 8-ANS, i.e. possesses all the properties of the molten globule intermediate state.

Anilino Naphthalenesulfonates↗
PubMed1996

Use of fluorescence decay times of 8-ANS-protein complexes to study the conformational transitions in proteins which unfold through the molten globule state.

The conformational transitions starting with the native protein, passing the molten globule state and finally approaching the unfolded state of proteins was investigated for bovine carbonic anhydrase B (BCAB) and human alpha-lactalbumin (alpha-HLA) by means of fluorescence decay time measurements of the dye 8-anilinonaphthalene-1-sulphonic acid (8-ANS). Stepwise denaturation was realized by using the denaturant guanidinium chloride (GdmCl). It was shown that 8-ANS bound with protein yields a double-exponential fluorescence decay, where both decay times considerably exceed the decay time of free 8-ANS in water. This finding reflects the hydrophobic environment of the dye molecules attached to the proteins. The fluorescence lifetime of the short-time component is affected by protein association and can be effectively quenched by acrylamide, indicating that 8-ANS molecules preferentially bind at the protein surface. The fluorescence lifetime of the long-time component is independent of the protein and acrylamide concentration and may be related to protein-embedded dye molecules. Changes of the long lifetime component upon GdmCl-induced denaturation and unfolding of BCAB and alpha-HLA correlate well with overall changes of the protein conformation. The transition from native protein to the molten globule state is accompanied by an increase of the number of protein-embedded 8-ANS molecules, while the number of dye molecules located at the protein surface decreases. For the transition from the molten globule to the unfolded state was the opposite behaviour observed.

Acrylamide↗
PubMed1996

[Nutritional intake of daily diets in nursing homes for the aged. I--Energy, protein, fat, carbohydrate and fiber].

Daily diet from 20 nursing homes for the elderly in the German state of Hessen was collected over a period of 7 days. Caloric free beverages were not included. After weighing and protocoling, the components of the meals were combined to one sample per day. Energy, protein, fat, carbohydrate and dietary fiber content was determined by analytical methods and by calculation using the nutrient table Federal Foodstuffs Key (Bundeslebensmittelschlüssel). Mean calculated contents exceeded analytical determined data except for dietary fibre. In comparison to the recommendations of the German Association for Nutrition (Deutsche Gesellschaft für Ernährung) concerning nutrient intake of the elderly, energy, fat and protein content of the daily diet were too high. Carbohydrate content did not reach the recommendations, being at least 50% of energy intake. It is remarkable that dietary fibre content exceeded the recommendations of 30 grams per day. In Hessen a similar study was already done in 1982. Regarding energy, protein, fat and carbohydrate content, only negligible changes could be stated since that time.

Aged↗
PubMed1996

Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany.

Previous studies of cognition enhancers have mainly focused on insufficiently defined groups of cognition disorders, e.g., "cerebral insufficiency". With regard to the various biological changes in senile dementia of Alzheimer's type (SDAT) and in vascular dementia (VD), which together make up the great majority of senile dementias, many authors have encouraged different studies of these types of dementias, especially since both can be diagnosed clinically with satisfying certainty. Since primary care physicians treat the majority of elderly and demented patients, they have their own experience with cognition enhancers. We were therefore interested to know, how far these physicians differ in their treatment of SDAT and VD. We performed a representative survey (response rate 83.2%; 145 family physicians and 14 neuropsychiatrists) in the Goettingen area. A written case vignette described a 70-year-old widow with moderate dementia and vascular risk factors which are easily treated with drugs. Two versions were randomly assigned, in which (version A) either a "typical" VD history or a typical SDAT history (version B) were described. After perusal, the physician was asked whether and which drugs he would choose to treat the cognitive disorders in this patient. Most frequently, piracetam (A/B: 25.6%/30.9%), ginkgo biloba (24.4%/28.4%), and nimodipine (14.1%/25.9%) were considered. Aspirin was cited by 29.5%(A) and 17.3%(B) of the physicians respectively. As far as the type of dementia was concerned, significant differences were found only for co-dergocrine, which was preferred in SDAT. The following inter-group trends were observed: family physicians considered ginkgo biloba more often than nimodipine or co-dergocrine. The results show the apparent importance of cost-and safety aspects, while the type of dementia has hardly any impact. The latter impression corresponds to the results of drug trials demonstrating no different efficacy. In our opinion, aspirin was not sufficiently taken into consideration.

Adult↗
PubMed1996

Mucosal enzyme activity for butyrate oxidation; no defect in patients with ulcerative colitis.

BACKGROUND: Butyrate is an important energy source for the colon and its metabolism has been reported to be defective in ulcerative colitis. One mechanism for defective butyrate metabolism in patients with ulcerative colitis could be an enzyme deficiency in the beta-oxidation pathway of butyrate. AIMS: This study was undertaken to measure the activity of each enzyme involved in the beta-oxidation pathway of butyrate in colonic epithelium. PATIENTS: Patients with ulcerative colitis (n = 33), Crohn's colitis (n = 10), and control subjects with colorectal cancer or diverticular disease (n = 73) were studied. METHODS: Analysis was carried out using fluorometric and spectrophotometric techniques on homogenised epithelial biopsy specimens. RESULTS: Significantly increased butyryl CoA dehydrogenase activity was found in mucosa from patients with ulcerative colitis (33.2 (28.3, 38.1) mumol/g wet weight/min:mean (95% CI)) compared with activity in mucosa from control patients (24.3 (20.9, 27.7) mumol/g wet weight/min:mean (95% CI)) p < 0.02. No significant increase in activity of the enzymes butyryl-CoA synthetase, crotonase or hydroxybutyryl-CoA dehydrogenase was found in patients with ulcerative colitis. In contrast the mucosal thiolase activity was significantly lower in those patients with quiescent colitis (3.21 (2.61, 3.81) mumol/g wet weight/min:mean (95% CI)) when compared with control mucosa (5.69 (5.09, 6.29) mumol/g wet weight/min:mean (95% CI)) p < 0.001. However, mucosal thiolase activity increases with the age of the donor patient and differences in the age range of the patient groups probably account for this finding. CONCLUSIONS: This study shows no substantial deficiency of enzyme activity in the beta-oxidation pathway of butyrate in the mucosa of patients with ulcerative colitis in histological remission.

Adolescent↗
PubMed1996

Specific targeting of human papillomavirus type 16 E7 oncogene with triple-helix forming purine oligodeoxyribonucleotides.

Molecular mechanical calculations (computer modelling), optical DNA melting experiments and co-migration assay were used to assess stable helix formation at homopurine-homopyrimidine-rich target sites present in the human papillomavirus type 16 E7 oncogene (positions 656-673 on the genome map). The target sequence, either present in the E7 oncogene obtained by PCR technique or prepared from oligodeoxyribonucleotides (ODNs), can be specifically recognised by different 17-merpurine ODNs designed to form antiparallel or parallel triple helices. These "in vitro" experiments realised with rather long purine ODNs having a high degree of specificity, open the way for "in vivo" tests focused on E7 oncogene targeting and suppression.

Base Sequence↗
PubMed1995

[Factors influencing the prescribing of nootropic drugs. Results of a representative inquiry in Lower Saxony].

AIM OF INVESTIGATION: To discover (1) to what extent patients' wishes and the extent of any abnormality of brain performance influence the frequency with which "nootropic" drugs (those thought to affect brain activity, e.g. piracetam, pyritinol, or improve cerebral circulation, e.g. xanthine derivatives, Ginkgo biloba, secale alkaloids, calcium antagonists) are prescribed; (2) the medical practitioner's expectations of the effectiveness of such medications. METHOD: In a personal interview, 145 family doctors and 14 neurologists in private practice in the Göttingen area of Germany (participation rate: 83.2% of those asked to participate) were questioned about fictitious cases (case 1: mild memory problem with or without expressed wish for medication; case 2: moderate dementia, of Alzheimer or multi-infarct type). The previously arranged interviews, which took place in the doctors' practice rooms, consisted of standardized open questions to the written case reports. RESULTS: Regardless of the wish of the patient and the extent and type of the abnormal brain function about 70% of all participating doctors would prescribe those drugs, even though about 56% had doubts about their effectiveness. About 28% expected a positive effect on brain performance. A nearly equal proportion of doctors would continue an existing drug regimen as would prescribe one. CONCLUSION: The prescription of the named group of drugs is influenced less by medical criteria than by factors which concern doctor-patient relationship.

Adult↗
PubMed1995

Primary structure of human amphiphysin, the dominant autoantigen of paraneoplastic stiff-man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14.

Amphiphysin is a protein peripherally associated with synaptic vesicles. It is expressed in many neurons, certain endocrine cell types, and spermatocytes. Autoantibodies against amphiphysin occur in patients afflicted with a rare neurologic autoimmune disease, paraneoplastic Stiff-Man syndrome. To provide a basis for the understanding of anti-amphiphysin autoimmunity, we have cloned cDNAs and determined the primary structure of human amphiphysin. Comparison with chicken amphiphysin defines domains of low and high amino acid sequence conservation. As a candidate for heritable disorders of the nervous system, endocrine tissues or male fertility, the human amphiphysin gene was mapped to chromosome 7, region p13-p14.

Animals↗
PubMed1995

Sleep disturbances in the demented elderly: treatment in ambulatory care.

We report the results of a representative survey in Lower Saxony, Germany, that focused on the treatment of sleep disturbances in the moderately demented elderly. Two written sample case histories (vignettes) described either a vascular demented patient suffering from nocturnal wandering or an Alzheimer's-type demented patient without apparent psychotic or behavioral (sleep) disorder. These were randomly assigned and presented to 145 family physicians and 14 neuropsychiatrists working in private practice by a trained investigator, who then conducted a standardized interview with the physicians. The study was representative of physicians (response rate: 83.2%). In response to the question concerning how they would treat the patient's sleep disturbances, about 20% of the physicians (with respect to both versions) answered that they would not choose drugs. More than 40% considered neuroleptics to be the drugs of choice. Benzodiazepines, antidepressants and other substances were seldom considered. No significant difference was noted in the response to the two different case histories. The results allow for the conclusion that non-drug treatments, which (at least initially) should be the treatment of choice, are mainly disregarded by the majority of the ambulatory care physicians. The reason for this seems to be a lack of education in sleep medicine and also in geriatric medicine.

Aged↗
PubMed1995

Reasons for prescribing cognition enhancers in primary care. Results of a representative survey in Lower Saxony, Germany.

With regard either to the controversial debate about the efficacy of cognition enhancers (CEs) or to the high costs which the frequent prescription of these drugs causes the German health system's economy, we wanted to know what physicians expect from a therapy with these drugs. We performed a representative survey (response rate 83.2%) in Lower Saxony, Germany from February to July 1993. We designed two written case vignettes which described either a patient with slight memory problems or a moderately demented patient who also suffers from common systemic disorders. In a face-to-face interview 145 general practitioners and primary care internists (family physicians) and 14 community neuropsychiatrists answered the question, whether they would prescribe CEs to each of the patients described and what they would expect from this therapy. 70.4% of all physicians would prescribe a cognition enhancer to the slightly impaired patient and 63.5% to the multimorbid moderately demented patient, respectively. More than 50% of the family physicians would not expect any positive therapeutic effect in both patients, while the neuropsychiatrists did so in 57.1% in the patient with slight memory disturbances and in 35.7% in the moderately demented patient. A positive effect on cognition was expected by 28.2% of all physicians in the slight and by 18.3% in the moderately impaired patient, respectively. Other reasons mentioned were amelioration of cerebral perfusion and drive, as well as effects on disease progression. In conclusion, the results of this study clearly demonstrate that cognition enhancers are prescribed in spite of major doubts in their efficacy.

Aged↗
PubMed1995

The role of L-carnitine in pediatric cardiomyopathy.

Metabolic and genetic factors underlie some forms of cardiomyopathy in childhood. A variety of inborn errors of metabolism can impair mitochondrial energy production, or beta-oxidation, in the heart and lead to myocardial dysfunction. L-Carnitine, an essential element of beta-oxidation, transports fatty acids across the mitochondrial membrane for energy production. L-Carnitine deficiency syndromes are now well described as secondary to a variety of inborn errors of metabolism and often include cardiomyopathy in the clinical picture. Despite traditional therapies for cardiomyopathy, mortality for this disorder remains at well over 50%. Review of reports of L-Carnitine supplementation studies and results from our own trial underscore the importance of its role in cardiac function and demonstrates that there is likely a subpopulation of patients with cardiomyopathy responsive to L-carnitine treatment.

Cardiomyopathies↗
PubMed1994

[Ambulatory treatment of sleep disorders in the aged].

An enquiry into the handling by medical practitioners of sleeping problems among elderly patients was conducted in southern Lower Saxony by personal interview, combined with a standard questionnaire. A typical case report had been drafted concerning a 70-year-old, previously healthy widow: her complaints were "nonspecific" and could be classified as an example of either depression, of the onset of senile dementia or as within normal limits for age. This case report was presented by two interviewers to 145 general practitioners (GPs) and 14 neurologists in private practice (response rate of 83.2%) who were asked how they would have treated the patient's sleeping disorder. 30.3% of the GPs and 14.3% of the neurologists would initially not have prescribed medication. Only GPs (19.5%) mentioned possible herbal medication. Sedative neuroleptics were preferred by 57.1% of neurologists and 26.2% of GPs, while benzodiazepines would have been given by 14% of both groups. Antidepressive drugs and chloral hydrate were chosen less often (5.7% and 2.5%, respectively). These data support the finding of a high frequency of neuroleptic prescriptions given to the elderly. They also make clear that the possibility of treatment without drugs is usually not sufficiently explored.

Aged↗
PubMed1994

Pyruvate dehydrogenase deficiency: molecular basis for intrafamilial heterogeneity.

Two half-brothers and their mother had symptomatic pyruvate dehydrogenase complex deficiency. The infants had severe congenital lactic acidosis, seizures, and apneic spells and died at the ages 3 and 4 months. The mother was less symptomatic with mental retardation, truncal ataxia, and dysarthria. The residual pyruvate dehydrogenase activities in cultured skin fibroblasts from the 2 infants and their mother were 7, 15, and 10% of control values. Immunoblot analysis showed negligible amounts of E1 alpha and E1 beta subunits of the complex. Northern blot analysis for the E1 alpha subunit showed normal results. In the 2 sons, complementary DNA sequence analysis revealed a cytosine to thymine mutation in exon 4, resulting in a change of arginine 127 to tryptophan in the E1 alpha subunit. Restriction enzyme analysis of the polymerase chain reaction product representing exon 4 of the E1 alpha gene revealed that the mother was a heterozygotes. Complementary DNA restriction analysis and methylation analysis of the X chromosome DXS255 loci revealed skewed activation of the mutant allele, consistent with the deficient pyruvate dehydrogenase activity in the mother's fibroblasts. The milder maternal phenotype is consistent with variable X-inactivation patterns in different organs of female heterozygotes.

Base Sequence↗
PubMed1994

Diagnosis of dementia in primary care: results of a representative survey in lower Saxony, Germany.

To investigate whether an early diagnosis of dementia is established, whether a differentiation is made between vascular and primary degenerative etiology, and whether treatable causes of dementia are considered in primary care, we performed a survey using three written sample case histories describing slight memory impairment (case 1) or moderate dementia (case 2a: vascular dementia; case 2: degenerative dementia of Alzheimer type). The combinations 1 and 2a or 1 and 2b were randomly assigned and presented to ambulatory-care physicians (145 general practitioners and primary care internists and 14 neuropsychiatrists in private practice) in Göttingen and rural surroundings by a trained investigator who then performed a standardized interview. The study was representative (response rate 83.2%). For the sample case with slight memory complaints 13.8% of all physicians arrived at a primary diagnosis of depression and 44.0% considered depression for differential diagnosis. Senile dementia of Alzheimer type was considered less often. In the sample cases with moderate dementia according to established scientific criteria, there was a striking under-diagnosis of dementia, and in both cases an over-diagnosis of underlying vascular etiology. Treatable causes of dementia, such as possible drug interactions and substance abuse, were considered only by a minority of physicians. In conclusion, memory deficits seem to be regarded mainly as consequences of disturbed cerebral perfusion, and dementia as well as depression and drug adverse effects seem to be under-diagnosed in primary care.

Aged↗
PubMed1994

Some new properties of DNA-YOYO-3 homodimer complexes revealed by electrophoresis and fluorescence lifetime measurements.

The DNA bis-intercalator oxazole homodimer (YOYO-3: 1,1'-(4,4,7,7-tetramethyl-4,7-diazaundecamethylene)-bis-4-[3-methy l- 2,3-dihydro-(benzo-1,3-oxazole)-2-methylidene]-quinolinium tetraiodide) specifically alters the electrophoretic pattern of covalently closed circular (CCC) DNA molecules. Thus, YOYO-3 seems to remove the CCC DNA supercoils and induces the appearance of additional bands by changing the linking number. It also promotes an unusual "star" activity for the restriction enzyme Hind III. Fluorescence lifetime measurements indicate that YOYO-3 is capable of binding to DNA by bis- and mono-intercalation.

Benzoxazoles↗
PubMed1994

Crystalloid versus blood cardioplegia in coronary by-pass surgery. A prospective, randomized, controlled study in 100 consecutive adults.

In a prospective randomized trial we investigated the benefit of blood versus asanguinous cardioplegia in routine coronary by-pass grafting. One hundred consecutive adult patients were randomly assigned to two groups: Group A (53 patients) received cold blood cardioplegia and group B (47 patients) had standard St. Thomas solution. In all patients we combined ante- and retrograde administration, in group A warm reperfusion was carried out before aortic declamping. Aortic cross clamp times, amount of cardioplegic solution and blood potassium levels at the end of cardio-pulmonary by-pass were higher in group A than in group B. The need for inotropic support at the end of the operation as well as in the postoperative period was more frequent in the crystalloid cardioplegia group. The occurrence of atrial fibrillation showed no clear correlation to the kind of cardioplegia used. Perioperative infarction was less frequent in the blood cardioplegia group (3.7% vs 6.3%; p < 0.01) and 30-day-mortality was nil (0% vs 3.2%; p < 0.01). Hospital stay did not differ between the two groups. In this clinical trial we could demonstrate the superiority of blood versus crystalloid cardioplegia in routine coronary by-pass grafting. Ante- and retrograde delivery of cold blood cardioplegia followed by warm reperfusion is a safe and simple method yielding satisfactory results.

Adult↗