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Biomedical subjects

C Wolf

Publications and source records attributed to C Wolf.

At least 127 records · Page 7Linked to original sources
PubMed1996

Matrilysin expression in human prostate carcinoma.

The metalloproteinases, a multigene family of metal-requiring enzymes, have been suggested to play a role in tumor invasion and metastasis. Previously, we demonstrated that human primary prostate tumors express higher levels of matrilysin and gelatinase A mRNA than normal prostate does. In the study presented here, we used in situ hybridization and immunohistochemical staining of serial sections of paraffin-embedded primary prostate tumors to compare the sites of matrilysin and gelatinase A expression and protein localization. These results confirmed the epithelial nature of matrilysin expression and protein localization. In contrast, gelatinase A mRNA was localized to the interstitial stroma, whereas the protein was associated with the epithelial tumor cells. In situ hybridization was also used to demonstrate that gelatinase B expression was restricted to macrophages infiltrating the tumors. Proteins isolated from an additional set of frozen tumor specimens were analyzed by western blotting to determine the relative amounts of matrilysin in the active and proenzyme forms. The western analyses demonstrated that in all cases in which matrilysin was detected, at least some of the enzyme was in the active form. These results are discussed with respect to the possible role these enzymes may play in prostate tumor progression.

Amino Acid Sequence↗
PubMed1996

Synthesis and pharmacology of combined histamine H1-/H2-receptor antagonists containing diphenhydramine and cyproheptadine derivatives.

The classical histamine H1-receptor antagonists diphenhydramine (3a) and cyproheptadine (9) and their derivatives (3b-d, 10) were connected with a 2-guanidinothiazole containing structure (28) derived from the H2-receptor antagonist tiotidine in order to obtain combined H1-/H2-receptor antagonists. The two moieties were not directly linked together, but were separated by a polymethylene spacer and a polar group (nitroethenediamine or urea). Thus 12 compounds were obtained that proved in vitro to possess high H1- and H2-receptor antagonist activity at the isolated guinea-pig ileum (H1) and the isolated guinea-pig right atrium (H2), respectively. The incorporation of the diphenhydramine as well as the cyproheptadine component provides high affinity to H1-receptors. The tricyclic cyproheptadine and its 10,11-dihydro derivative (30-32, 34), however, cause a decrease of H2-receptor antagonist potency compared to the diphenhydramines (29a-d, 33a-d). Using nitroethenediamine as the polar group is apparently more favourable to H1- and H2-receptor affinity as the urea function. All compounds elicit a dual mode of competitive and noncompetitive antagonism. Among the novel compounds the nitroethenediamines with 4-fluoro- or 4-methyl-substituted diphenhydramine as H1-receptor antagonist moiety (29c, d) display the most potent H1- and H2-receptor antagonist effects. The presented concept is a very promising way to combine H1- and H2-receptor antagonist properties in one molecule.

Animals↗
PubMed1996

Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz and the lethal acrodysgenital syndromes.

UNLABELLED: The Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterized by dysmorphic facial features with abnormal limbs and genitalia. Two forms have been recognized based on clinical course and severity: the classical SLO (type I) and the lethal acrodysgenital syndrome (type II). Type I SLO has been recently ascribed to a defect in cholesterol synthesis. Taking advantage of a series of seven patients including five type I and two type II SLO, we describe micrognathia, severe microcephaly, major ante and post natal growth retardation and feeding difficulties as consistent features in the disease. In addition, we give support to the presence of abnormal cholesterol levels in the lethal acrodysgenital syndrome but find no correlation between plasma sterol levels and the clinical severity of the disease. CONCLUSION: The identification of the same biochemical defect in both types of Smith-Lemli-Opitz Syndrome suggests that despite major discrepancies in clinical course and severity, type I and type II SLo are probably allelic disorders.

Child↗
PubMed1996

Are coping strategies related to disease outcome in early breast cancer?

A consecutive series of 107 women with early breast cancer were investigated for coping strategies and disease outcome 5 to 6 years after primary surgical treatment (mastectomy or lumpectomy). Coping was assessed several times during a 3-year investigation period by the Zurich and Freiburg Questionnaires of Coping with Illness (ZQCI, FQCI). Data analysis revealed no significant correlations between coping strategies and the target variable "death from breast cancer". However, significant relations were found between postsurgical tumour size (p < or = 0.01), positive histological node status (p < or = 0.01) and death from breast cancer. The results of a discriminant analysis also indicated that somatic parameters are more important for the course of breast cancer disease than psychological aspects of coping. The role of psychosocial variables for the outcome of cancer disease remains unclear and further studies in this field are necessary.

Adaptation, Psychological↗
PubMed1996

1,2,3-Trithiane-5-carboxylic acid, a first contact allergen from Asparagus officinalis (Liliaceae).

BACKGROUND: Although hundreds of cases of allergic contact dermatitis caused by asparagus have been described in the literature, the responsible allergens are still unknown. OBJECTIVE: Fresh asparagus shoots were purchased in early April. Juice and ether extracts were prepared and stored in a deep freezer until chemical investigations and patch tests could be performed. Known constituents were obtained from investigators who have isolated asparagus components. METHODS: Asparagus-sensitive patients were patch tested with the juice or fresh parts of asparagus and four constituents. One of the compounds was synthesized to get greater amounts for experimental sensitization in guinea pigs. RESULTS: All patients gave positive results with the fresh asparagus and 1,2,3-trithiane-5-carboxylic acid, one of its constituents. Experimental sensitization showed that asparagus has a weak to moderate sensitizing capacity. 1,2,3-Trithiane-5-carboxylic acid showed a similar sensitizing power in the experiments. 1,2,3-Trithiane-5-carboxylic acid is a plant growth inhibitor occurring in asparagus mainly in the early phase of the season. CONCLUSION: For the first time, a sulfur-containing growth inhibitor could be determined as a contact sensitizer in an edible plant. A second sensitizing constituent was detected, of which the structure could not yet be elucidated completely.

Adult↗
PubMed1996

Changes in serum sterols of rats treated with 7-dehydrocholesterol-delta 7-reductase inhibitors: comparison to levels in humans with Smith-Lemli-Opitz syndrome.

The impaired conversion of 7-dehydrocholesterol to cholesterol, as a result of a permanent inhibition of the activity of 7-dehydrocholesterol-delta 7-reductase, has been reported in the Smith-Lemli-Opitz (SLO) syndrome (1, 2). For the purpose of experimental teratology, an animal disease model consisting of the offspring of pregnant rats treated with AY 9944 or BM 15766, inhibitors of 7-dehydrocholesterol-delta 7-reductase, was established. The present study compares the profiles of sterols in rat serum, obtained after transient treatment with inhibitors, with profiles of sterols obtained from patients with the permanent enzyme defect. AY 9944 (single dose of 50, 75, or 100 mg/kg) or BM 15766 (60, 75, or 90 mg/kg per day for 11 days) induces hypocholesterolemia and accumulation of 7-dehydrocholesterol and aberrant sterols in rat serum. The aberrant sterols in the treated rats are similar to those detected in human SLO patients by gas chromatography coupled to mass spectrometry (1, 3, 4) and were identified as 7- and 8-dehydrocholesterol, two trienols (I and II), and 19-nor-5,7,9(10)-cholestatrien-3 beta-ol. The time- and dose-dependences of the biochemical alterations are compared to the teratogenic abnormalities induced by inhibitors. The dietary cholesterol supplementation that suppresses embryo malformations induced by AY 9944 prevents severe hypocholesterolemia and decreases the aberrant sterol levels. As a function of time after intoxication, the 8-dehydrocholesterol to 7-dehydrocholesterol ratio increases, suggested that 8-dehydrocholesterol is derived from the gradual conversion of the accumulated 7-dehydrocholesterol. The ratio of 8-dehydrocholesterol to 7-dehydrocholesterol is higher in human SLO than in the animal disease model. This may be explained by a permanent block in 7-dehydrocholesterol-delta 7-reductase in SLO compared to a transient inhibition of this enzyme in the animal model.

Animals↗
PubMed1996

[Percutaneous "high risk" angioplasty with prophylactic cardiopulmonary support. High risk PTCA with mechanical circulatory support].

With improved technology and development of several mechanical assist devices, the indications of percutaneous transluminal coronary revascularization have been extended. In 39 patients (30 men, mean age = 60.1 +/- 8.1 years) with angina pectoris or heart failure, with poor operative risk-benefit ratio and ejection fraction < 35% and/or target vessel supplying > 50% of the viable myocardium, we performed assisted percutaneous transluminal coronary revascularization. Intraortic balloon counterpulsation (n = 16), extracorporal circulation (n = 21), or hemopump (n = 2) were used for mechanical support. Complete 6-week follow up was possible in 27 patients. An improvement of left-ventricular function (patients with EF < or = 35% demonstrated an improvement: 27 +/- 7 vs 36 +/- 10%, p < 0.05), heart failure (patients with EF < or = 35% demonstrated an improvement of maximal oxygen uptake: 14 +/- 4 vs 17 +/- 4 ml/kg/min; p < 0.05) and a marked improvement of angina (23/38 demonstrated CCS-improvement of at least one class) was found. Hospital mortality was as low as 2.6%. Major postinterventional complications included nonfatal myocardial infarction (n = 2), fatal retroperitoneal bleeding (n = 1), pulmonary edema (n = 1), nonfatal ventricular fibrillation (n = 1), cerebrovascular event without residual (n = 1), and deep vein thrombosis (n = 4). In conclusion, assisted percutaneous revascularization was successful in a high risk subset of patients with increased surgical risk and/or poor ventricular function.

Aged↗
PubMed1996

[Increased secretogranin II protein and mRNA expression in C cells of the thyroid in Hashimoto's thyroiditis].

Secretogranin II (chromogranin C) has been demonstrated in normal and hyperplastic C cells of the thyroid as well as in medullary thyroid carcinoma. Both by immunohistochemistry and immunoblotting it was found that C cells and medullary thyroid carcinomas contain substantially less secretogranin II when compared to chromogranins A and B. Secretoneurin, a biologically active protein endoproteolytically processed from secretogranin II, has been found to have a potent chemotactic activity towards monocytes. This and the finding that histamine specifically induces secretogranin II mRNA in cultured bovine chromaffin cells may indicate a possible role of this peptide in inflammatory conditions. The aim of the present study was to investigate secretogranin II both on the mRNA and protein level on routinely processed tissues from 18 cases with Hashimoto's thyroiditis. In contrast to normal, hyperplastic, and neoplastic C cells, the C cells in cases with Hashimoto's thyroiditis showed increased secretogranin II mRNA as well as protein (secretogranin II and secretoneurin) expression. Our results support the concept that secretogranin II/secretoneurin may be involved in inflammatory conditions. Further studies are necessary to elucidate whether secretogranin II is of biological relevance in Hashimoto's thyroiditis.

Animals↗
PubMed1996

[Is inpatient rehabilitation of patients with chronic obstructive lung disease (COPD) useful? Results of a prospective 1-year follow-up study].

Success of inpatient therapy for patients with chronic obstructive pulmonary disease (COPD) has been assessed in a prospective study of 54 patients (mean age = 63.8y). During hospital stay (mean duration = 27.6d) FEV1% of predicted improved from 42.5% on admission to 51.9% on discharge (p < 0.001). Quality of Life (QoL) (p < 0.05) and Health Satisfaction (p < 0.001) improved significantly. The 22 drop-outs revealed a significantly more depressive coping strategy but did not differ from the remaining 32 patients regarding lung function, sociodemographic data and QoL. One year after the hospital stay the remaining 32 patients showed a still improved FEV1% (46.4%, p < 0.05) and Health Satisfaction (< 0.05) but QoL scores relapsed to entry levels. Better pulmonary long-term effects were achieved by patients with high QoL scores on entry; subjects that tended most to wishful thinking as a coping strategy had worse pulmonary outcome.

Adaptation, Psychological↗
PubMed1995

Characterization of monoclonal antibodies against stromelysin-3 and their use to evaluate stromelysin-3 levels in breast carcinoma by semi-quantitative immunohistochemistry.

Stromelysin-3 (ST3) is a matrix metalloproteinase which is expressed in fibroblastic cells of most human invasive carcinomas and represents a potential new prognostic indicator. Expression of recombinant ST3 forms in Escherichia coli from cDNA constructs indicated that high levels of expression were achieved when the ST3 pro-domain was deleted. The putative mature form of ST3 thus produced and recovered from bacterial inclusion bodies was used to prepare monoclonal antibodies (MAbs) against ST3 by immunization of BALB/C mice. Ten hybridomas producing MAbs against ST3 were obtained and analyzed for their ability to detect endogenous ST3 in breast cancer and in conditioned media from human fibroblasts. One of these MAbs (5ST-4A9) was found to be suitable for the routine detection of ST3 on breast cancer tissue sections, thus opening the possibility to evaluate ST3 prognostic value in breast cancer using semi-quantitative immunohistochemistry.

Animals↗
PubMed1995

Blood sphingomyelins from two European countries.

The objectives of this study were to isolate and analyse human blood sphingomyelins from two European populations which have significant differences in both the composition of dietary fat source and the rate of mortality from coronary heart disease. Blood samples have been taken from healthy adult volunteers from a Greek (Thessaloniki) and a French (Paris) region. The sphingomyelin fraction from red blood cells and plasma, separately, have been isolated by thin-layer chromatography and analysed by mass spectrometry after soft chemical ionisation with gas ammonia. The conditions used gave spectra with three discrete areas which correspond to ions coming from sphingoid bases, fatty acids and ceramides. Eight sphingoid bases have been detected in both red blood cells and plasma. Sphingosine was the major contributor. The rest of the sphingoid bases have 16 to 19 carbon atoms and 0 to 2 double bonds. Fourteen fatty acids, the same for red blood cells and plasma, have been detected with 16 to 26 carbon atoms and 0 to 2 double bonds. Palmitic acid was the most abundant fatty acid. Thirty eight ceramides have been detected in red blood cells and forty in plasma. Thirty six ceramides were common in red blood cells and plasma. Statistically significant differences (P < 0.01) have been detected between the two populations for some sphingoid bases, fatty acids and ceramides. Differences have also been found between the two populations in the degree of saturation of these sphingomyelin parts. These differences are attributed to (a) high monounsaturated fat, olive oil, consumption by Greeks and (b) other environmental and genetic factors. It is suggested that the detected differences between the two populations contribute to the different coronary heart disease rates observed among Greeks and French.

Adult↗
PubMed1995

Effect of lead on blood pressure in occupationally nonexposed men.

To determine if low-level exposure to lead has an effect on arterial blood pressure, demographic and clinical data of a group of 507 males without any occupational exposure to lead were analyzed in a retrospective study. The following variables were included in the analysis: age, height, weight, nicotine consumption, alcohol intake, blood lead, systolic blood pressure, diastolic blood pressure, and erythrocyte count. The effects of the variables age, weight, height, alcohol intake, nicotine consumption, and blood lead on blood pressure were investigated by stepwise linear regression analysis. The diastolic as well as the systolic blood pressure was significantly influenced by Body Mass Index, age, and alcohol. A significant effect of lead could be found only for diastolic blood pressure. None of the possible interactions were significant enough to merit inclusion in the statistical model. Regarding the strength of the effects on diastolic blood pressure we find that lead ranks after age, weight. In conclusion, this study shows that lead has an effect on diastolic arterial blood pressure in a survey of a group of middle-aged, occupationally nonexposed men.

Adult↗
PubMed1995

Phospholipids with a short acyl chain modulate phospholipase and acyltransferase activities.

1-Acyl lysophosphatidylcholine prepared from egg yolk has been chemically reacylated to form decanoyl, dodecanoyl, myristoyl and palmitoyl derivatives of phosphatidylcholine. The liposomes formed by these semi-synthetic phospholipids have been characterized by calorimetry, X-ray diffraction and fluorescence probe methods. Asymmetric phosphatidylcholines tend to promote formation of excimers of a codispersed fluorescent phospholipid (1-palmitoyl-sn-2-(1-pyrenedecanoyl)-L-alpha-phosphatidic acid) (2 mol%). Excimer formation is correlated with the rate of hydrolysis of the fluorescent anionic phospholipid by Crotalus venom phospholipase A2. Codispersion with the semi-synthetic phosphatidylcholine of cholesterol or unsaturated fluid lecithin modulated both excimer formation and the susceptibility of the fluorescent probe to hydrolysis by venom phospholipase A2 at 22 degrees C. Similar results were obtained with hydrolysis of a radiolabelled substrate, 1-palmitoyl-sn-2-[1-14C]linoleoylphosphatidylethanolamine, codispersed with the semi-synthetic phosphatidylcholine. Enrichment of rat hepatocyte plasma membranes with semi-synthetic asymmetric phosphatidylcholines was mediated by incubation of membranes with phospholipid dispersions in the presence of a phospholipid exchange protein. Enrichment of the membranes with semi-synthetic phosphatidylcholines of between 30 and 60% of the membrane phosphatidylcholine was achieved. The resulting alteration of the biomembrane is associated with a decreased activity of endogenous membrane phospholipase A2 acting on extramembranous radiolabelled substrate vesicles. By contrast, the activity of acyl-CoA:lysophospholipid acyltransferase is increased in membranes enriched with highly asymmetric phospholipids.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1995

Polyunsaturated fatty acid enrichment increases ultraviolet A-induced lipid peroxidation in NCTC 2544 human keratinocytes.

The influence of cell enrichment with fatty acids with increasing degree of unsaturation on the ultraviolet A-induced formation of lipid-peroxidation products (thiobarbituric acid reactive substances [TBARS]) has been investigated in NCTC 2544 human keratinocytes. A 48-h preculture of cells in controlled medium supplemented with unsaturated fatty acids resulted in a marked increase in TBARS appearance under ultraviolet A exposure. This effect was dependent upon the degree of unsaturation of the fatty acids, with the following order of efficiency: arachidonic > linolenic > linoleic > oleic acid. For arachidonic acid (AA), the potentiating effect on ultraviolet A-induced lipid peroxidation was dependent upon the fatty acid concentration, with about a 2.5-fold increase in TBARS formation in cells pre-cultured with 5 x 10(-5) M AA, then exposed to a UVA dose of 13 J/cm2. The increase in TBARS formation by AA was almost totally prevented by supplementation of cells with 5 x 10(-5) M vitamin E, whereas buthionine sulfoximine, a chemical which depletes cell glutathione, potentiated lipid peroxidation. These results suggest that the nature of the fatty acids of cellular lipids could influence the response of keratinocytes to ultraviolet A, and especially the ultraviolet A-induced lipid peroxidation.

Antimetabolites↗
PubMed1995

Direct molecular analysis of myotonic dystrophy in the German population: important considerations in genetic counselling.

Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat at the DM locus on chromosome 19. Direct genomic analysis in the German population was carried out on 18 DM families, six families with equivocal diagnosis, 69 subjects with equivocal clinical diagnosis, and 100 controls using the polymerase chain reaction (PCR) and a refined Southern protocol. In the majority of the cases molecular analysis confirmed the clinical diagnosis. These included seven cases of congenital DM (CDM) with widely differing gene expansions and instabilities. In most DM families the expanded fragment became larger in successive generations, but we also identified four families with contractions and two families that showed stability of the enlarged fragment during transmission. In four clinically defined DM patients we were unable to detect enlarged CTG repeats. Sequencing of each exon of the DM gene in two of these patients failed to show any mutations. Our cases have important implications for genetic counselling of DM families, highlighting both the diagnostic value of direct genomic analysis and its limitations.

Adult↗
PubMed1995

[Legal guardianship in psychiatric consultation].

The goal of the new guardianship law in Germany, in effect since 1992, is to enable the mentally ill to lead as independent a life as possible and as long as possible without any legal action. However, a comparison of 81 (1991) cases decided under the old law and 82 (1992) decided under the revised law as part of a psychiatric liaison service at a large general hospital showed that in practice the benefits for one of the main groups affected, elderly patients with dementia, might be relatively small. There are two reasons for this: the legal decision about incompetency has become more complicated and the social circumstances of the individuals affected can be changed very little by the law.

Activities of Daily Living↗
PubMed1995

[Causal attributions and coping with illness by breast cancer patients: results of a longitudinal study].

The present 3-year longitudinal study investigated the relationship between causal attribution and coping mechanism. Data were collected in a group of 66 breast cancer patients by self-report questionnaires. Three issues were addressed: 1. How do the patients explain the cause of their illness? 2. Do the subjective causes change over the course of three years? 3. What kind of relationship can be found between the causal attributions and the coping mechanism of the patients? Results showed a predominance of psychological attribution. Only little statistical prove could be found for changes between the four ratings. Analysing the individual data of the patients however revealed changing perceptions for about half the patients. A relationship between psychological attribution and depressive coping and problem solving as well were found.

Adaptation, Psychological↗