Biomedical subjects

S Wallner

Publications and source records attributed to S Wallner.

16 recordsLinked to original sources

PubMed2006

Expression of Hugl-1 is strongly reduced in malignant melanoma.

The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelial-mesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses were associated with advanced stage of the disease. Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Further, downregulation of MMP2 and MMP14 (MT1-MMP) and re-expression of E-cadherin was found in the Hugl-1-expressing cell clones supporting a role of Hugl-1 in EMT. Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression.

Blotting, Western↗

PubMed2001

Acute effects of nicorandil on glucose tolerance in subjects with borderline fasting blood glucose levels.

The acute effect of the anti-ischemic potassium channel opener nicorandil on glucose tolerance and post-challenge insulin levels was investigated in 11 subjects (6 males and 5 females, age 59 +/- 2 years) with borderline fasting blood glucose in a single blinded randomised study. All participants were submitted to two oral glucose tolerance tests in randomised order, once without any premedication and once 30 minutes after oral administration of 20 mg nicorandil. This single dose of nicorandil significantly increased blood glucose levels at 120 minutes (173 +/- 16 vs. 150 +/- 11 mg/dl, p < 0.05 by ANOVA) and 180 minutes (106 +/- 11 vs. 88 +/- 7 mg/dl, p < 0.05 by ANOVA) after ingestion of 75 mg of glucose. Serum insulin levels were not significantly altered. In conclusion we suggest that controlled studies in patients with coronary artery disease should be performed to investigate whether long term treatment with nicorandil increases progression rates from impaired glucose tolerance to type-II diabetes and/or from normal to impaired glucose tolerance with a possibly negative impact on the course of cardiovascular disease in comparison to conventional anti-anginal drugs.

Administration, Oral↗

PubMed2001

The alpha-amino group of L-arginine mediates its antioxidant effect.

Antioxidant effects may constitute part of the possible antiatherogenic effects of the amino acid L-arginine. These antioxidant properties were further characterized in a model of lipoprotein oxidation. Oxidation of lipoproteins in unfractionated human serum was continuously monitored by a fluorescent probe. The antioxidant effects of L-arginine, N-alpha-acetyl-arginine and vitamin E in combination with L-arginine were measured after initiation of free radical generation with either copper or 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). The half-time of the fast propagation rate for copper-induced lipoprotein oxidation increased after incubation with L-arginine in a dose-dependent manner (P < 0.01). N-alpha-acetyl-arginine did not show such effects. Vitamin E and L-arginine show different effects on copper-induced oxidation, the former increasing only lag-time, the latter increasing only propagation rate, and do not have reciprocal effects. In contrast to copper-induced oxidation, L-arginine increased the lag-time of AAPH-induced lipoprotein oxidation (P < 0.01), with no effect on the propagation rate at physiological concentrations. Again, N-alpha-acetyl-arginine did not show any antioxidant effects. Our experiments provide further evidence that mechanisms other than serving as a substrate for the NO-synthase could be involved in the antiatherosclerotic effect of L-arginine. In addition, our experiments clearly show, that the antioxidant effect of L-arginine is due to a chemical moiety different from that serving as the substrate for NO biosynthesis.

Amidines↗

PubMed2000

Leptin deficiency due to lipid apheresis: a possible reason for ravenous hunger and weight gain.

OBJECTIVE: To investigate how extracorporal cholesterol lowering therapy affects circulating leptin levels in patients with ravenous hunger after treatment and permanent weight gain. DESIGN: A case report. SUBJECT: 51 y old caucasian male patient with moderate chronic renal failure. MEASUREMENTS: Serum Leptin concentration (RIA, Linco Research Inc, St. Louis, MO, USA), total cholesterol, low density lipoprotein cholesterol, blood glucose levels, calorie intake by food records. RESULTS: During treatment total cholesterol was reduced by 50%. Serum Leptin levels showed a 42% reduction at the end of treatment, that by far exceeds the physiological diurnal variation. Calorie intake was significantly increased on days of treatment. CONCLUSION: We conclude that this artificial reduction in circulating leptin plays an important role in the pathogenesis of ravenous hunger and weight gain under extracorporal cholesterol lowering therapy in this case.

Blood Glucose↗

PubMed1999

Effects of intensified lifestyle modification on the need for further revascularization after coronary angioplasty.

BACKGROUND: In patients with coronary artery disease (CAD), a rate of restenosis as high as 50% is observed after percutaneous transluminal coronary angioplasty (PTCA). Frequently, this results in further revascularization procedures. Lifestyle intervention has been shown to slow the progression of CAD and to reduce cardiovascular events after myocardial infarction. However, no information exists whether such treatment influences the rate of restenosis in patients with CAD. The present study was performed to investigate the effects of an intensified lifestyle intervention on the need for further revascularization procedures in patients with established CAD after successful PTCA. DESIGN: A total of 60 patients were included and randomized to either conventional treatment by cardiologists and general practitioners or additional intensified lifestyle intervention in a diabetes and metabolism outpatient clinic for 12 months. The mean observation time after successful PTCA was 26 months. The primary outcome variable was the need for further revascularization procedures because of clinical restenosis. Secondary outcome variables were lifestyle-related measures. RESULTS: Intervention resulted in a reduction in body weight and blood pressure, and in increased physical activity. Furthermore, nutritional habits were changed towards less fat intake, and body composition changed towards a higher proportion of fat-free mass. The need for further revascularization procedures was reduced from a total of 14 out of 32 in the conventionally treated group to 3 out of 28 in the intervention group. This resulted in an event-free survival probability of 0.89 in the intervention group and 0.57 in the control group (P = 0.0055, log rank) with a resulting relative risk of 0.26 (95% CI 0.09-0.74). CONCLUSION: In conclusion, our data strongly suggest that intensified lifestyle modification is able to reduce the need for further revascularization procedures after PTCA in patients with CAD.

Angina Pectoris↗

PubMed1999

Effect of an individualised training programme during weight reduction on body composition: a randomised trial.

OBJECTIVE: To study the effect of a standardised training programme focusing on maintenance of fat free mass during weight reduction by energy reduction in obese children. DESIGN: Randomised trial of physical training programme and dietary advice (group A) versus dietary advice alone (group B). SUBJECTS: Thirty obese children and adolescents (14 group A, 16 group B) participated in the 12 week long programme; 20 children (10 group A, 10 group B) were also reassessed after one year. MEASUREMENTS: Fat free mass was estimated from the resistance index, obtained by bioelectrical impedance analysis at baseline, after four, eight, and 12 weeks in all subjects, and after one year in 20 subjects. RESULTS: The mean (SD) change in fat free mass was significantly different between the two groups after 12 weeks (group A, 2.68 (3.74) kg; group B, 0.43 (1.65) kg). The change in body weight after one year was inversely correlated with the change in fat free mass after 12 weeks (r = -0. 44), as assessed in the 20 subjects. CONCLUSIONS: A standardised training programme as used in this study can prevent reduction in fat free mass during weight loss in obese children. Reduction in fat free mass during weight reduction might be a risk factor for regain of weight.

Adipose Tissue↗

PubMed1998

Forearm composition contributes to differences in reactive hyperaemia between healthy men and women.

BACKGROUND: Post-ischaemic reactive hyperaemia in the forearm has been suggested as a marker of resistance vessel function. The contribution of forearm composition to the kinetics of reactive hyperaemia is largely unknown. The body composition of men and women differs in that women have a higher body fat content and less lean body mass. METHODS: In the present study, we investigated whether the kinetics of reactive hyperaemia in the forearm in 14 healthy subjects (seven men and seven women) show gender-specific differences and whether forearm composition contributes to such differences. RESULTS: Peak reactive hyperaemic flow as well as 1-min-flow debt repayment (measured by venous occlusion plethysmography) were significantly higher in male than in female study participants. This difference was explained to > 60% by gender-specific differences in forearm relative muscle mass (as determined by magnetic resonance imaging). The half-life of the reactive hyperaemic response, on the other hand, was not different between men and women and did not show an association with forearm muscle. CONCLUSION: Our results demonstrate that forearm composition must be considered if peak reactive hyperaemic or flow debt repayment is used as a target, and that dynamic measurements of the reactive hyperaemic process are more suitable to describe the function of resistance arteries than single-point observations.

Adipose Tissue↗

PubMed1997

Vascular effects of L-arginine: anything beyond a substrate for the NO-synthase?

L-arginine supplementation is hypothesized to reduce endothelial dysfunction and atherogenesis via increased biosynthesis of nitric oxide. Here we describe superoxide scavenging properties of arginine as an additional aspect which needs to be considered. Furthermore, arginine reduced copper-induced lipid peroxidation, indicating that superoxide anions essentially contribute to this process. In intact endothelial cells, L-arginine but not D-arginine diminished superoxide release and reduced cell-mediated breakdown of nitric oxide. Our data indicate that the reported vascular effects of L-arginine supplementation might involve an increased bioavailability of nitric oxide due to its superoxide scavenging properties beside a potential increased NO biosynthesis.

Animals↗

PubMed1997

Trace elements in coronary heart disease: Impact of intensified lifestyle modification.

Concentrations of 14 trace elements (Bi, Cd, Co, Cs, Cu, Hg, Mn, Pb, Rb, Sb, Sn, Sr, Tl, and Zn) were determined by inductively coupled plasma mass spectrometry (ICP-MS) in 120 whole-blood and 121 plasma samples of 56 patients with angiographically documented coronary heart disease (CHD). One serum and two whole-blood reference materials were analyzed for quality control. At baseline, patients had elevated Co plasma as well as diminished Cu blood concentrations compared to healthy adults. The Zn concentrations in whole blood were below or at the lower end of the normal range, but the concentrations in plasma were elevated. All other trace elements were within the normal concentration ranges for healthy adults. After initial investigations, patients were randomly assigned to an experimental group (N = 27) and to a usual care group (N = 29). Experimental group patients were prescribed a lifestyle program that included a low-fat diet and a weekly moderate exercise. Patients were examined at baseline, after 6 and 12 mo for clinical assessment and fasting venous blood samples. No significant time-course changes in concentrations of trace elements in blood and plasma during the clinical treatment in both groups of patients could be observed. The experimental group patients lost weight and had lower blood pressure after 12 mo compared to baseline. The interventional therapy reduced the need for further revascularization procedures.

Aged↗

PubMed1997

Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity.

The present study was carried out to evaluate the effect of a low-dose intravenous supplementation of L-arginine on insulin-mediated vasodilatation and insulin sensitivity. The study was performed in healthy subjects (n = 7) and patients with obesity (n = 9) and non-insulin-dependent diabetes mellitus (NIDDM) (n = 9). Insulin-mediated vasodilatation was measured by venous occlusion plethysmography during the insulin suppression test, evaluating insulin sensitivity. Experiments were performed twice in each subject in the presence or absence of a concomitant infusion of L-arginine (0.52 mg kg-1 min-1). L-Arginine restored the imparied insulin-mediated vasodilatation observed in obesity (22.4 +/- 4.1%, P < 0.01 vs. without L-arginine) and NIDDM (20.3 +/- 3.2%, P < 0.01 vs. without L-arginine). In healthy subjects, no effect on insulin mediated-vasodilatation was observed (24.8 +/- 3.1% vs. 21.4 +/- 3.1%). Insulin sensitivity was improved significantly (P < 0.001) in all three groups by infusion of L-arginine. No effect of L-arginine was observed on insulin, insulin-like growth factor I (IGF-I), free fatty acids (FFAs) or C-peptide levels during the insulin suppression test. Our data indicate that defective insulin-mediated vasodilatation in obesity and NIDDM can be normalized by intravenous L-arginine. Furthermore, L-arginine improves insulin sensitivity in obese patients and NIDDM patients as well as in healthy subjects, indicating a possible mechanism that is different from the restoration of insulin-mediated vasodilatation.

Adult↗

PubMed1997

Influence of autologous blood transfusion on natural killer and lymphokine-activated killer cell activities in cancer surgery.

BACKGROUND AND OBJECTIVES: Immunosuppression associated with blood transfusion may influence postoperative infection rates. It may also affect the prognosis of patients treated surgically for colorectal cancer. To control this effect, study protocols have applied autologous blood donation programs, which are thought to be immunologically neutral. However, evidence has emerged that blood donation itself might have suppressive effects on natural killer (NK) cell activities. At present, there are no data available on the effects of autologous blood transfusion on NK or lymphokine-activated killer (LAK) cells. This might be of interest as LAK cells may be active in tumor control. MATERIALS AND METHODS: 26 patients who underwent surgical resection for colorectal cancer, were assigned at random into two groups: (1) autologous blood donation and transfusion, or (2) allogeneic blood transfusion. NK and LAK activities were determined before blood donation, at surgery, and on the 3rd and 8th postoperative day. RESULTS: Blood donation induced a small decrease in NK and LAK activities. The postoperative courses of the two groups differed. In the allogeneic group, NK activity (-50%, p = 0.018) and LAK activity decreased (-60.7%, p = 0.043), whereas in the autologous group the decline in LAK was less pronounced (-33.7%, p = 0.091), and their NK activity even increased (+17.4%, p = 0.315). NK activity was modulated differently in the two study groups (0.0036). Differences in LAK activities were found between the 3rd and 8th day postoperatively (p = 0.354). CONCLUSIONS: In patients receiving autologous blood transfusion, postoperative suppressed NK and LAK activities were modulated. This implies that autologous blood transfusion is not immunologically neutral, but has an intrinsic immunomodulatory potential.

Aged↗

PubMed1997

[Effect of chromium yeast and chromium picolinate on body composition of obese, non-diabetic patients during and after a formula diet].

The objective of this study was to assess the effects of chromium yeast and chromium picolinate on lean body mass during and after weight reduction with a very-low-calorie diet. 36 obese (BMI 33.7 +/- 5.4 kg/m2), non-diabetic patients aged 45 +/- 6 years undergoing a 8-week very-low-calorie diet followed by a 18-week maintenance period. During the whole 26 week treatment period subjects received either placebo or chromium yeast (200 micrograms/d) or chromium-picolinate (200 micrograms/d) in a double-blind manner. Body weight was measured as BMI and body composition after calculation from skinfold thickness. As a result all three groups showed comparable weight loss after 8 and 26 weeks. Lean body mass was reduced in all groups after 8 weeks. However, after 26 weeks chromium picolinate supplemented subjects showed increased lean body mass (p < 0.029) whereas the other treatment groups still had reduced lean body mass. Chromium picolinate, but not chromium yeast, is able to increase lean body mass in obese patients in the maintenance period after a very-low-calorie diet without counteracting the weight loss achieved.

Adult↗

PubMed1994

Endobronchial actinomycosis.

Endobronchial actinomycosis was found to be the cause of right-sided atelectasis and haemoptysis in a 57 year old man without predisposing conditions. Fibreoptic bronchoscopy revealed occlusion of the intermediate bronchus by yellow-white masses. The diagnosis was confirmed histologically and by positive Actinomyces culture from bioptic material. Prolonged antibiotic treatment resulted in complete recovery, without need for surgical resection.

Actinomycosis↗

PubMed1987

The anemia of thermal injury: partial characterization of an erythroid inhibitory substance.

Anemia is one of a large number of systemic changes occurring in severely burned patients and has a multifactorial etiology including hemorrhage, hemolysis, and depression of the rate of erythropoiesis. In previous studies, it was found that serum of burned humans and animals contained a substance(s) capable of interfering with red cell colony formation in vitro. Here are reported studies done in an attempt to characterize further the inhibitory activity. The molecular weight was more than 50,000 daltons by ultrafiltration. By gel filtration an inhibitory region was identified with an approximate molecular weight range of 140-290,000. Treatment of sera with proteolytic enzymes resulted in loss of activity suggesting that the inhibitory substance(s) was a protein. Ion exchange chromatography indicated that the inhibitor was an acidic protein. It is suggested that this material participates in the pathophysiology of the anemia of thermal injury by depressing red cell production.

Adult↗

PubMed1984

The haematopoietic response to burning: studies in an animal model.

Changes in haematopoiesis which occur in humans after burning injury may have important effects on morbidity and mortality. Because of the heterogeneity of burn patients we studied the regulation of blood cell formation which occurs in an animal using an established mouse model. Mice received a 20 per cent third degree scald injury on the back. Serial studies of a variety of haematopoietic parameters including stem cell, bone marrow and peripheral blood findings were done post burn. Although anaemia occurred frequently after injury red blood cell survival studies and examination of the stool for occult blood showed that neither haemolysis nor blood loss were primary causes of the anaemia. Bone marrow erythroid stem cells fell markedly post burn and this was associated with the development of a substance in serum capable of inhibiting red cell colony formation but not white cell colony formation of normal marrow cells. Reticulocytosis occurred but was mild and the anaemia was primarily of the aregenerative type. Partial compensation for the depressed marrow erythropoiesis occurred in the spleen with an increase in erythroid colony-forming cells and erythroblasts. Marked granulocytosis occurred in the peripheral blood and bone marrow. There was an increase in splenic granulocytic stem cells post burn. Megakaryocytosis was striking in the bone marrow and spleen and there was an increase in peripheral blood platelet count. Evidence of immune stimulation included an increase in the size of the spleen and an increase in peripheral blood and splenic lymphocytes. Correlations of many of these findings suggested that the events were not occurring at random but that the changes in haematopoiesis were linked together. We speculate that the anaemia was the result of the increase in granulopoietic and thrombopoietic effort seen post burn.

Anemia↗

PubMed1983

Regulation of granulopoiesis following severe thermal injury.

Neutropenia often accompanies septicemia in burned patients. This paradox suggests a defect in the regulation of granulopoiesis. Colony stimulating factor (CSF) produced by the monocyte-macrophage system is an important regulator of granulocyte production. We followed serial serum CSF levels and peripheral blood leukocyte differential counts in 22 patients with greater than 30% burns. Six patients (mean burn, 58%) developed Gram-negative septicemia and died (Group I). Sixteen patients (mean burn, 38%) had no fatal septicemias (Group II). Nonsurvivors had initially low levels of CSF and developed persistent monocytopenia. Survivors, in contrast, had prompt rises in CSF and developed monocytosis. The presence of monocytopenia and low CSF levels in Group I suggests an abnormality in the stimulatory arm regulating granulopoiesis. Such a defect may play a role in the development of fatal septicemia following severe thermal injury.

Adult↗