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W Schmidt

Publications and source records attributed to W Schmidt.

At least 217 records · Page 12Linked to original sources
PubMed1998

[Effect of high performance sports on energy metabolism].

The knowledge about metabolism and muscular fatigue has been considerably improved during the recent years. Intramuscular pH should not generally be discussed as a factor of cellular fatigue as it has been shown to increase transiently at the beginning and to be very differently affected in ST-(6,9) and FT-fibers (6,2) at the end of exercise. During maximum exercise, we assume changes of muscle membrane potential due to increasing interstitial potassium concentrations as an important performance-limiting factor. The role, lactate is playing during exercise, has to be thought over. Its production by the binding of two protons to the pyruvate molecule is necessary for an intensive anaerobic and aerobic metabolism. The lactate molecules itself represent a source of energy, which is preferentially used by the heart muscle and by ST-fibers working at lower intensity. During long term endurance events, the glycogen stores are assumed to be a limiting factor. However, no direct casual relationship between glycogen and fatigue mechanisms has been found hithertoo. The anaerobic glycolytic metabolism decreases during long lasting exercise as a result of lowered glycogen stores. Therefore, metabolic acidosis cannot be observed after ultra-long endurance events. In contrast, a respiratory alcalosis is the common finding.

Adolescent↗
PubMed1998

Human tumour xenografts in nude mice: chemotherapy trials with titanocene dichloride in different dosages.

PURPOSE: In this study new cytostatic therapies with titanocene dichloride in different dosages for the treatment of ovarian cancer are analyzed on human tumour xenografts in nude mice. The aim was to compare the effects of different dosages of titanocene dichloride on the growth of human tumour xenografts and nude mice body weight. METHODS: Biopsy material from one human ovarian carcinoma was expanded and transplanted into 52 nude mice. The treatment protocol included one experiment that consisted of the following six treatment groups: titanocene dichloride 3 x 10 mg/kg, titanocene dichloride 3 x 20 mg/kg, titanocene dichloride 3 x 30 mg/kg, titanocene dichloride 1 x 30 mg/kg, titanocene dichloride 1 x 40 mg/kg and a control group treated with 0.9% saline. Treatment groups were evaluated in terms of average daily increase in tumour volume and average daily body weight increase on nude mice. The slope factors alpha and beta of the body weight and tumour volume changes were calculated. RESULTS: Titanocene dichloride in the dosage of 3 x 30 mg/kg and 3 x 20 mg/kg brought about a significant reduction in tumour volume (p < 0.05) compared to the control group and to the treatment group under medication with titanocene dichloride 1 x 30 mg/kg. There were no significant changes in the body weight of nude mice. CONCLUSION: We found titanocene dichloride to be effective in the reduction of tumour volume increase in nude mice. Titanocene dichloride could be an active chemotherapeutic drug in women with ovarian carcinoma not responding to standard therapies.

Animals↗
PubMed1998

Effects of vinorelbine and titanocene dichloride on human tumour xenografts in nude mice.

PURPOSE: In this study, the new antineoplastic agents titanocene dichloride and vinorelbine are compared to cisplatin and paclitaxel using a human ovarian cancer xenograft model. METHODS: Biopsy material from one native human ovarian carcinoma was expanded and transplanted into 48 nude mice. The animals were divided into six treatment groups: cisplatin 3x4 mg/kg, paclitaxel 5x26 mg/kg, vinorelbine 1x20 mg/kg, titanocene dichloride 3x30 mg/kg, titanocene dichloride 3x40 mg/kg and a control group treated with 0.9% saline. Treatment groups were evaluated in terms of average daily increase in tumour volume and average daily body weight increase of the nude mice based on slopes of least square regressions performed on individual animals. The slope factors alpha and beta of the body weight (alpha) and tumour volume changes (beta) within each group were calculated. RESULTS: A statistically significant decrease (p<0.05) in body weight of the experimental animals was shown in groups treated with paclitaxel (alpha = -0.6878) and titanocene dichloride 3x40 mg/kg (alpha = -0.7194) compared to the control group which was treated with 0.9% saline (alpha = -0.2643). Significant body weight changes were not observed in the comparison of the remaining treated groups (cisplatin: alpha = -0.4552, vinorelbine: alpha = -0.5606, titanocene dichloride 3x30 mg/kg: alpha = -0.6173 to the control group. A significant reduction (p<0.05) of the increase tumour volume (vinorelbine: beta = 5.260, paclitaxel: beta = 0.478, titanocene dichloride 3x30 mg/kg: beta = 10.283, titanocene dichloride 3x40 mg/kg: beta = 5.768) was shown in treated groups except for cisplatin (beta = 18.722) compared to the tumour bearing control group (beta = 30.136). A statistically significant reduction of the increase in tumour volume occurred under paclitaxel medication compared to the group treated with cisplatin. CONCLUSION: We found titanocene dichloride to be effective as vinorelbine and more effective than cisplatin. Vinorelbine seems to be a very effective antineoplastic agent with a significantly higher cytostatic effect than cisplatin. Both titanocene dichloride and vinorelbine provide new therapeutic options in women with ovarian carcinoma not responding to standard chemotherapies.

Animals↗
PubMed1998

Correlation between immunoreactivity for transglutaminase K and for markers of proliferation and differentiation in normal breast tissue and breast carcinomas.

We investigated immunohistochemically localization and expression of transglutaminase K (TGK) in normal breast tissue (n = 10) and in breast carcinomas (n = 30). Transglutaminase K was compared with the staining patterns of cytokeratin 10, Ki-67, p53, estrogen and progesterone receptors in these tumors. Weak to strong membrane bound immunoreactivity to TGK was detected in 17 out of 30 breast carcinomas analyzed. TGK staining was heterogeneous with visual differences between individual tumour cells. Ninety percent of normal breast tissues revealed no immunoreactivity to TGK. Both intensity of TGK immunostaining and number of TGK-positive cells were upregulated in breast carcinomas as compared to normal breast tissue. Analyzing coexpression of TGK with cytokeratin 10, Ki-67, p53, ER and PR, no statistically significant correlation was found. Our findings indicate that: (I) TGK is upregulated in breast carcinomas as compared to normal breast tissue. (II) Upregulation of TGK in breast carcinoma is not exclusively induced by alterations of epithelial differentiation or proliferation, but by different, unknown mechanisms. (III) Upregulation of TGK in breast carcinomas may play an important role in the regulation of tumour cell invasive properties by modulating cell-matrix interactions or by facilitating the assembly of matrix and tissue remodeling.

Antibodies, Neoplasm↗
PubMed1998

Leiomyosarcomas of the female genital tract: a clinical and histopathological study.

INTRODUCTION: Leiomyosarcomas are malignant tumours showing smooth muscle differentiation. They represent approximately 25% of all uterine sarcomas and slightly over 1% of all uterine malignancies. The purpose of the present retrospective review is to relate clinical and pathological findings of leiomyosarcomas of the female genital tract to prognosis. MATERIAL AND METHODS: During 1972-1992 eleven patients had diagnosed uterine leiomyosarcomas treated at the Department of Gynecology of the University of Saarland. The hospital records of all patients were reviewed and complete primary treatment had been performed at this center. RESULTS: The mean age was 46.92 years (SD: +/-13.85). Atypical uterine bleeding and pelvic discomfort were the most common presenting complaints (72.7%). The mean follow-up time was 59.60 months (20-96 months). Overall 2-year survival was 70% and overall 5-year survival 30%. The overall survival of patients in FIGO-stage I was 57.14%, in FIGO-stage II 100%, in FIGO-stage III 0% and in FIGO-stage IV 0%. CONCLUSION: The primary therapy should consist of an operation as radical as possible. Treatment with organ preserving seems to be reasonable if the patient desires children. Also, chemotherapy might provide a hopeful sign in the improvement of survival rates.

Adult↗
PubMed1998

The influence of tamoxifen on the maturation index of vaginal epithelium.

PURPOSE: The estrogenic effect of tamoxifen on vaginal epithelium in postmenopausal women with breast cancer was evaluated over a period of more than 48 months. METHODS: The tamoxifen group consisted of 118 postmenopausal patients, control group I of 30 postmenopausal women with breast cancer receiving no tamoxifen or hormonal replacement therapy and control group II of 40 postmenopausal women without breast cancer taking no hormones. We determined the maturation index of the vaginal epithelium. Pearson's chi-square-test and t-test for independent samples were used in the statistical analysis. RESULTS: The maturation index increased under tamoxifen therapy within the first 24 months from 0.4026 before taking tamoxifen (n = 64) to 0.6066 (n = 162, p < 0.0001) and in the following 24 months to 0.6325 (n = 122, p < 0.0001). Under tamoxifen intake of more than 48 months, an additional small increase of the maturation index to 0.6735 (n = 42, p < 0.0001) could be noticed. The maturation index in the tamoxifen group was statistically significantly higher (p < 0.0001) than in the control groups (control group I: 0.3975, p < 0.0001; control group II: 0.4102, p < 0.0001). CONCLUSION: An apparent increase in the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen could be demonstrated.

Aged↗
PubMed1997

Alternative pathways of xanthone biosynthesis in cell cultures of Hypericum androsaemum L.

The biosynthesis of xanthones was studied in cell cultures of Hypericum androsaemum L. We have detected a new benzophenone synthase, for which the preferred substrate is benzoyl-CoA, itself supplied by 3-hydroxybenzoate:coenzyme A ligase. The stepwise condensation of benzoyl-CoA with three molecules of malonyl-CoA, catalyzed by benzophenone synthase, yields 2,4,6-trihydroxybenzophenone. This intermediate is subsequently converted by benzophenone 3'-hydroxylase, a cytochrome P450 monooxygenase. These biosynthetic steps, leading to the formation of 2,3',4,6-tetrahydroxybenzophenone, represent an alternative pathway to that recently proposed for cell cultures of Centaurium erythraea [Peters et al., Planta (1997) in press].

Acyl Coenzyme A↗
PubMed1997

Abnormal predominance of IgG in HIV-specific antibodies produced by short-term cultured duodenal biopsy specimens from HIV-infected patients.

The aim of our study was to analyze HIV-specific humoral immunity in the intestinal mucosa at different stages of HIV infection in comparison with serum and saliva. Duodenal biopsy specimens from 30 AIDS patients and 9 HIV-infected patients without AIDS were cultured for 48 hours. Culture supernatants, as well as simultaneously obtained serum and saliva samples, were adjusted to the same immunoglobulin concentrations and tested for HIV-specific IgG and IgA by Western blot. The HIV antigen pattern differed clearly between IgA and IgG but was similar for each isotype independent of its origin (i.e., serum, saliva, or biopsy specimen supernatants). Short-term cultured duodenal biopsy specimens from HIV-infected patients at all stages produced predominantly IgG, which was broadly reactive with HIV antigens. Lower titers of HIV-specific IgA, which recognized few antigens, were found, mostly the glycoprotein gp160. At later stages of the disease compared with earlier stages, the reaction pattern of mucosal IgA from saliva and biopsy supernatants was even more restricted; secretory component was frequently absent. The abnormal predominance of HIV-specific IgG over IgA in mucosal secretions may result from abnormal antibody production in the mucosa rather than from serum leakage. Mucosal inflammation induced by HIV-IgG immune complexes and insufficient immune exclusion by secretory IgA may not only lead to increased mucosal HIV replication but may also contribute to gastrointestinal disease in HIV-infected patients.

Adult↗
PubMed1997

Delayed treatment with rolipram protects against neuronal damage following global ischemia in rats.

In this study the effect of post-treatment with rolipram, an inhibitor of cAMP phosphodiesterase, on neuronal damage following global ischemia was evaluated. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 minutes. Rolipram was administered 6 hours after onset of ischemia and thereafter the following 7 days daily once at a dose of 0.3 or 3.0 mg/kg intraperitoneally. Four weeks after ischemia the amount of intact neurons in the hippocampus and in the striatum was assessed following perfusion fixation. The ischemia-induced neuronal damage in the CA1 sector of the hippocampus and in the striatum was reduced by rolipram at either dose. The present results show that treatment with rolipram reduces ischemic neuronal damage at a therapeutic window of 6 hours.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

[The effect of a lower stimulation frequency on the AV synchronicity of VDD pacemakers].

BACKGROUND AND OBJECTIVE: Implantation of a VDD pacemaker (ventricular pacing; dual sensing [atrial and ventricular]; dual response [triggered + inhibited]) together with a single VDD electrode catheter restores synchronous AV ventricular stimulation in patients with higher-grade AV block and intact sinus function. If higher-frequency stimulation occurs it may be a sign of pacemaker malfunction or of inadequate pacemaker programming. This study was undertaken to determine, at first follow-up examination, in how many patients with a VDD pacemaker VVI stimulation occurred more than 5% of the time; how such patients differed from those with 5% or fewer VVI stimulations; and whether a changed program reduced the proportion of VVI stimulations. PATIENTS AND METHODS: 67 consecutive patients were tested 1 to 3 months after implantation of the Unity VDD pacemaker (Sulzer Intermedics). The frequency of VVI stimulations was determined via a diagnostic pacemaker memory store. After intermediate analysis, programming was optimized and the patients then re-tested 12 months after the initial implantation. RESULTS: At the first follow-up examination 54 patients had VVI stimulations of < or = 5% (0.5 +/- 0.9%) and 13 had > 5% of the time (19.8 +/- 10.7%). The two groups differed significantly from one another in their lower intervention frequency (< or = 5% VVI stimulations: 47 +/- 6/min; > 5% VVI stimulations: 58 +/- 5/min). In particular, the pacemakers in patients with > 5% VVI stimulations had been significantly more often programmed to values of > 50/min. As a result, the pacemakers of these patients were reprogrammed to a lower frequency. A year after implantation there was no longer any difference in the lower intervention frequency, 44 +/- 4/min, between patients with initially > 5% VVI stimulations and those with initially < or = 5% stimulations. At the same time, the proportion of VVI stimulations fell to 4 +/- 6%, with 67% of patients having AV synchronicity of > 95%. INTERPRETATION: At first follow-up, patients with > 5% VVI stimulations differed from those with < or = 5% stimulations with regard to an increased lower intervention frequency. In most of these patients the proportion of AV stimulations was increased to > 95% by reducing the lower intervention frequency to < or = 50/min.

Aged↗
PubMed1997

Retinal ischemia induced by the intraluminal suture method in rats.

In a model of transient focal cerebral ischemia in male Sprague-Dawley rats, which is induced by the intraluminal suture method, the acute effects on the electrical function of the retina were monitored by recording the electroretinogram. The electroretinogram was recorded from halothane-anesthetized rats before, during and after vascular occlusion through the intraluminal suture method for 180 min. During vascular occlusion the amplitude of the a- and b-wave were markedly suppressed. Upon reperfusion the a-wave recovered immediately. During reperfusion up to 48 h the amplitude of the b-wave increased to approximately 50% of the pre-occlusion value did not fully recover. Immunohistochemistry of the retinas revealed that the vascular occlusion induced the expression of glial fibrillary acidic protein in retinal Müller cells. The present data suggest that the intraluminal suture method leads to retinal ischemia.

Animals↗
PubMed1997

Intestinal formation of hypoxanthine and uric acid during endotoxemia.

The objective of this study was to examine the intestinal metabolism of high-energy purine compounds as sensitive indicators of tissue ischemia during endotoxemia. Arterial (art) and portal venous (PV) concentrations as well as the intestinal net concentration changes of adenosine (ADO), hypoxanthine (Hypo), and uric acid (UA) were measured at baseline and after 60 and 120 min in rats that were subjected to a 1-hr continuous infusion of endotoxin (1.5 mg/kg; group E), and in control animals (group C). Furthermore, the arterial (SaO2) and portal venous oxygen saturation (S(PV)O2) was determined at the same time points. Animals in both groups remained normotensive throughout the study period and no differences in mean arterial blood pressure were observed. In both groups, adenosine concentrations remained constant throughout the study and no changes in the net concentration difference (NCD) of adenosine between arterial and portal venous blood were observed [ADO(NCD); baseline: group E, -23 +/- 46 nmole/L; group C, 17 +/- 84 nmole/L; 120 min: group E, 14 +/- 38 nmole/L; group C, 5 +/- 40 nmole/L]. In contrast to control animals, hypoxanthine and uric acid concentrations increased in arterial and portal venous blood in endotoxemic rats after 120 min. This was accompanied with an increase in the intestinal net concentration differences of both hypoxanthine and uric acid, indicating the gut as the predominant source of these two compounds during endotoxemia [Hypo(NCD); baseline: group E, -36 +/- 53 nmole/L; group C, -53 +/- 185 nmole/L; 120 min: group E, 538 +/- 211 nmole/L; group C, 99 +/- 100 nmole/L] [UA(NCD); baseline: group E, 2.04 +/- 1.62 micromole/L; group C, -0.04 +/- 1.11 micromole/L; 120 min: group E, 9.58 +/- 3.04 micromole/L; group C, 0.35 +/- 1.34 micromole/L]. Furthermore, in endotoxemic rats the portal venous oxygen saturation decreased despite unaltered arterial oxygen saturation [SaO2; baseline: group E, 95.2 +/- 0.9%; group C, 94.2 +/- 0.9%; 120 min: group E, 95.4 +/- 0.7%; group C, 96.4 +/- 0.9%] [S(PV)O2; baseline: group E, 86.2 +/- 3.1%; group C, 85.7 +/- 1.4%; 120 min: group E, 69.1 +/- 4.5%; group C, 82.3 +/- 1.9%]. These results indicate the presence of tissue ischemia in the intestinal tract during early, normotensive endotoxemia. Furthermore, because of the direct toxic damage mediated by oxygen radicals that are generated during the production of uric acid, intestinal mucosal injury observed during endotoxemia may be related to an enhancement of the ATP-degradation pathway.

Adenosine↗
PubMed1997

Generation of effective cancer vaccines genetically engineered to secrete cytokines using adenovirus-enhanced transferrinfection (AVET).

Cancer vaccines are based on the concept that tumors express novel antigens and thus differ from their normal tissue counterparts. Such putative tumor-specific antigens should be recognizable by the immune system. However, malignant cells are of self origin and only poorly immunogenic, which limits their capability to induce an anticancer immune response. To overcome this problem, tumor cells have been isolated, genetically engineered to secrete cytokine gene products and administered as cancer vaccines. We used adenovirus-enhanced transferrinfection (AVET), which allows high-level transient transgene expression, to introduce cytokine gene expression vectors into murine melanoma cells. The efficiency of AVET makes laborious selection and cloning procedures obsolete. We administered such modified tumor cells as cancer vaccines to syngeneic animals and investigated their impact on the induction of anticancer immunity. We found that IL-2 or GM-CSF gene-transfected murine melanoma cells are highly effective vaccines. Both of these cytokine-secreting vaccines cured 80% of animals which bore a subcutaneous micrometastasis prior to treatment, and induced potent antitumor immunity. The generation of antitumor immunity by these cytokine-secreting vaccines requires three different steps: (1) tumor antigen uptake and processing by antigen-presenting cells (APCs) at the site of vaccination; (2) migration of these APCs into the regional lymph nodes where T-cell priming occurs; (3) recirculation of specific, activated T-cells that recognize distinct tumor load and initiate its elimination. Extending our previously reported studies, we have now comprehensively analysed the requirements for effective antitumor vaccination in animals. This may also become the basis for treatment of human cancer patients.

Animals↗