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Biomedical subjects

W Vogel

Publications and source records attributed to W Vogel.

At least 253 records · Page 14Linked to original sources

Extraversion as a modifying factor in catecholamine and behavioral responses to ethanol.

Individual differences in catecholamine response to stress and ethanol were tested in extraverts and introverts on the basis of Eysenck's drug postulate claiming that introverts would be less susceptible to sedative drugs like ethanol. Forty-four healthy males received either 0.8 g/kg ethanol mixed into a drink of caffeine-free cola or a respective placebo and were tested with a stressful mental arithmetic task before and 40 min after the intake of the drink. Plasma catecholamines were determined from blood samples drawn at five defined intervals from an indwelling cannula and self-ratings on deactivation, relaxation, and anxiety were obtained as well as quality and quantity of performance in the arithmetic task. Results showed that there was no difference in catecholamine stress responses between introverts (Ex -) and extraverts (Ex +) before the drink, but that the intake of the fluid (both ethanol and placebo) resulted in higher norepinephrine (NE) increases in Ex - than in Ex +. The combined effects of ethanol and stress yielded larger responses of longer durations in Ex - than in Ex +. The concomitant psychological changes showed larger reductions in anxiety and increases in relaxation as well as larger decrements in quality of performance (% errors) in introverts in spite of their higher catecholamine increases. Thus, the predictions on the basis of arousal theory could not be verified experimentally and the drug postulate has to be modified in the sense that introverts probably have a higher depletion of NE in the central nervous system under physical but not under mental stress which is reflected by higher levels in the plasma and respective decreases in performance and activation.

Adult↗

Prevalence of hepatocellular carcinoma in alpha-1-antitrypsin deficiency.

The aim of the present study was to determine the prevalence of hepatocellular carcinoma in adults with heterozygous alpha 1-antitrypsin deficiency and to assess the presence of possible co-risk factors for the development of hepatocellular carcinoma. Two hundred and forty patients with cirrhosis of different aetiologies and 130 patients with alpha 1-antitrypsin deficiency without evidence of chronic liver disease were investigated. Out of the 240 patients with cirrhosis, 61 patients (25%) were found to have alpha 1-antitrypsin deficiency, 36 patients (15%) had chronic hepatitis C infection, 50 (21%) had chronic hepatitis B and 24 (10%) had hepatitis C and hepatitis B infection. Thirty patients (12%) had cryptogenic cirrhosis and 39 (16%) alcoholic cirrhosis. The prevalence of hepatocellular carcinoma in patients with alpha 1-antitrypsin deficiency-associated cirrhosis was comparable to that of hepatocellular carcinoma in patients with cirrhosis of other aetiologies. Positive viral markers were found in 67% of the patients with alpha 1-antitrypsin deficiency-associated cirrhosis with hepatocellular carcinoma. In contrast, in the group of 130 patients with alpha 1-antitrypsin deficiency but without clinical and laboratory signs of chronic liver disease, none was found to have hepatocellular carcinoma (p = 0.001). Our results indicate that heterozygous alpha 1-antitrypsin deficiency-associated cirrhosis is a risk factor for hepatocellular carcinoma, but this is due to chronic liver disease and not due to the metabolic disorder itself.

Adult↗

Alpha 1-antitrypsin phenotypes in patients with anti-neutrophil cytoplasmic antibody-positive vasculitis.

1. The genetic background of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis remains largely unknown. Recently a very high prevalence of medium and severe deficiency of alpha 1-antitrypsin was described in a small group of patients with Wegener's granulomatosis and c-ANCA. c-ANCAs are autoantibodies against proteinase 3, and alpha 1-antitrypsin is the main inhibitor of this enzyme. 2. alpha 1-Antitrypsin phenotypic polymorphism was determined by isoelectric focusing in 32 patients with c-ANCA-associated systemic vasculitis. Twenty-nine patients had Wegener's disease, two had microscopic polyarteritis and one suffered from idiopathic rapidly progressive glomerulonephritis. 3. Two patients were homozygous PiZZ and three were heterozygous PiMZ. These phenotype frequencies differed significantly from expected values, assuming Hardy-Weinberg equilibrium (P < 0.01). Compared with a control group of 868 healthy blood donors, these results meant a significant increase in the PiZ allele (0.0138 versus 0.1094, P < 0.001). 4. Furthermore, the serum of 47 patients with severe alpha 1-antitrypsin deficiency (PiZZ) was tested for the presence of ANCA. All sera were negative for c-ANCA and p-ANCA. None of the patients showed clinical signs of systemic vasculitis. 5. In conclusion, these data indicate that alpha 1-antitrypsin deficiency, despite being significantly more common in patients with c-ANCA-associated systemic vasculitis, is only a minor genetic risk factor for the development of this disease.

Adolescent↗

The male pseudohermaphrodite XX polled goat is Zfy and Sry negative.

The Polled mutation of the goat is inherited as an autosomal dominant trait. Homozygotes with a 60,XX karyotype develop into intersexes. We looked for the presence of Y-chromosomal sequences (Zfy and Sry) in a male pseudohermaphrodite polled goat by Southern blotting and PCR analysis. Molecular analysis revealed that this XX goat had no Sry sequence. It showed identical hybridization patterns, using the human SRY and ZFY probes at low stringency, with the normal XX female goat, whereas an XY male revealed prominent Sry and Zfy signals. Identical results were obtained from PCR analysis with the caprine Sry primers. The possible role of an autosomal recessive gene in the induction of testes and maleness is discussed.

Animals↗

[The significance of infection pathways for hepatitis C virus associated chronic liver disease].

The importance of hepatitis C virus (HCV) infection as a cause of chronic liver disease has become clear with the introduction of serologic detection methods. On the basis of epidemiologic evidence the parenteral way of infection has been considered to be the most important one. However, the epidemiologic data regarding the significant route of infection are still limited. To study the ways of HCV-infection and their possible influence on the course of the disease, 73 patients with chronic hepatitis C infection were examined. Setting was the out-patient department of Gastroenterology of our University Hospital. Patients history, completed by a questionnaire, laboratory findings and liver histology were analysed. The study indicated that in 50% of the patients transmission had occurred through parenteral infection, the other 50% had been infected through the non-parenteral (sporadic) way. The study revealed further that the way of infection has an influence on the progression of liver disease with the patients infected sporadically showing histologically more serious hepatic changes. In 50 patients HCV-infection was the only cause of their chronic liver disease, in 23 patients additional pathogenic factors were detected. These 23 patients showed a rapid progress of the disease. Therefore, HCV-infection cannot be considered any longer as a disease that is primarily transmitted parenterally. Due to the large number of sporadic infections, HCV-infection will continue to be of great epidemiologic importance even after the effective elimination of contaminated blood products.

Adolescent↗

[Bassini and Shouldice repair of inguinal hernia. A retrospective comparative study].

Between 1987 and 1991 394 primary inguinal hernias in 370 patients were treated in a series of 199 patients using Bassini repair and a consecutive series of 195 patients using Shouldice repair. No intraoperative complications were seen in either group. During hospitalisation time 2 early recurrences were seen after Bassini repair, but there were no significant differences in postoperative haematomas, wound infections and thromboembolic complications between both groups. Recurrence rate was 21.6% in Bassini repair after a mean observation period of 48 months and 2.6% in Shouldice repair after a mean observation period of 26 months. A higher rate of hypesthesia was found after Shouldice repair. There was no incidence of postoperative testicular atrophy, granuloma or hydrocele in both groups. According to the significantly lower recurrence rate and good acceptance by the patients the Shouldice procedure currently seems to be the best standard for inguinal hernia repair.

Adolescent↗

[Prognosis and life expectancy in primary biliary cirrhosis].

The aim of the present study was to investigate prognosis and life expectancy in patients with primary biliary cirrhosis. We retrospectively analysed 59 patients from western Austria over 15 years (mean 6 years). The results of the present study were compared with the average life expectancy of the population of western Austria and with the results of the Mayo study published in 1989. The mean survival time in our study was 112.7 months, 25% were dead by 132 months. Kaplan-Meier analysis showed a 95% probability to survive 1 year and a 84% probability to be alive at 5 years. Asymptomatic patients had a significantly better prognosis than symptomatic patients. In comparison with the Mayo study the patients in our study had a better prognosis and in comparison with the normal population a significantly worse life expectancy.

Adult↗

Familial occurrence of agonadism and multiple internal malformations in phenotypically normal girls with 46,XY and 46,XX karyotypes, respectively: a new autosomal recessive syndrome.

We report on 2 phenotypic sisters, one with 46,XY; the other with 46,XX. The 2 girls had similar related internal malformations, including agonadism, hypoplasia of the right pulmonary artery, hypoplasia of the right lung, isolated dextrocardia with complex vitium cordis, and diaphragmatic hernia (only sib 1) or omphalocele (only sib 2). This combination of malformations did not fit into any of the previously described syndromes. For this syndrome we suggest the acronym PAGOD ([hypoplasia of the] pulmo, and pulmonary artery, agonadism, omphalocele/diaphragmatic defect, dextrocardia). The occurrence of a basically similar set of malformations in 2 unlike sex is interpreted as evidence for autosomal recessive inheritance. The different gonosomal status excludes the Y chromosome as a responsible factor. The peculiar finding of a 46,XX sex chromosome constitution combined with agonadism and an intact urogenitral tract emphasizes the concept of secondary regression of Wolffian and Müllerian structures. The associated malformations of mesodermal structures can be interpreted as midline defects. We suggest that, from the developmental field perspective, secondary regression of midline structures including the gonadal anlage explains the pathogenesis reasonably well.

Abnormalities, Multiple↗

Induction of circulating IL-1 receptor antagonist by IFN treatment.

This study was undertaken to determine whether IFN induce IL-1 receptor antagonist (IL-1Ra), a specific inhibitor of IL-1. Plasma samples were obtained from healthy volunteers (n = 5) and patients with chronic hepatitis C (n = 5) treated with IFN-alpha, and from patients with renal cell carcinoma (n = 6) treated with IFN-gamma and assayed for IL-1Ra by a specific radioimmunoassay. Both types of IFN were administered subcutaneously. In vitro studies were carried out with PBMC from healthy volunteers. A single, low and nontoxic dose (1 x 10(6) U) of IFN-alpha induced circulating IL-1Ra, which reached peak levels within 12 h. This effect was dose-dependent and more pronounced with a higher dose (5 x 10(6) U). Peak IL-1Ra levels 12 h after 5 x 10(6) U IFN-alpha were 4.16 +/- 0.35 ng/ml in healthy volunteers and 5.7 +/- 0.73 ng/ml in patients with chronic hepatitis C (difference not significant). Thereafter levels declined but remained elevated for 24 h. IFN-gamma treatment led only to a modest increase of circulating IL-1Ra even at a dose of 400 micrograms; this dose, however, was associated with side effects similar to those seen after injection of 5 x 10(6) U IFN-alpha. PBMC stimulated with IFN-alpha or IFN-gamma produced IL-1Ra in vitro. The induction of IL-1Ra may contribute to the antiviral, anti-inflammatory, and antiproliferative effects of IFN.

Carcinoma, Renal Cell↗

Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation.

Regulation of cell proliferation, differentiation, and metabolic homeostasis is associated with the phosphorylation and dephosphorylation of specific tyrosine residues of key regulatory proteins. The phosphotyrosine phosphatase 1D (PTP 1D) contains two amino terminally located Src homology 2 (SH2) domains and is similar to the Drosophila corkscrew gene product, which positively regulates the torso tyrosine kinase signal transduction pathway. PTP activity was found to be regulated by physical interaction with a protein tyrosine kinase. PTP 1D did not dephosphorylate receptor tyrosine kinases, despite the fact that it associated with the epidermal growth factor receptor and chimeric receptors containing the extracellular domain of the epidermal growth factor receptor and the cytoplasmic domain of either the HER2-neu, kit-SCF, or platelet-derived growth factor beta (beta PDGF) receptors. PTP 1D was phosphorylated on tyrosine in cells overexpressing the beta PDGF receptor kinase and this tyrosine phosphorylation correlated with an enhancement of its catalytic activity. Thus, protein tyrosine kinases and phosphatases do not simply oppose each other's action; rather, they may work in concert to maintain a fine balance of effector activation needed for the regulation of cell growth and differentiation.

Amino Acid Sequence↗

The hepatic acute-phase proteins alpha 1-antitrypsin and alpha 2-macroglobulin inhibit binding of transferrin to its receptor.

Transferrin binding to human placental sites was inhibited by the acute-phase proteins alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-MG), whereas haptoglobin, C-reactive protein and ferritin displayed no such effect. In equilibrium saturation binding assays, the effective acute-phase proteins decreased the apparent affinity of the binding sites for transferrin, but the transferrin binding-site density Bmax. was not significantly changed. For instance, the addition of 30 microM alpha 1-AT increased the KD of transferrin from 8.46 +/- 1.51 nM to 21.6 +/- 3.04 nM; the Bmax. values were 1.17 +/- 0.18 pmol/mg of protein and 1.04 +/- 0.25 pmol/mg of protein respectively. In kinetic studies, alpha 1-AT decreased the association rate constant k+1 of the 125I-transferrin-binding-site complex from 2.18(+/- 0.21) x 10(7) M-1.min-1 to 3.99(+/- 0.18) x 10(6) M-1.min-1. In contrast, the dissociation rate constant k-1 was not changed (0.0948 +/- 0.002 min-1, 0.089 +/- 0.0017 min-1). On isoelectric focusing, no alteration in transferrin protein pattern or shift in isoelectric point was detected in the presence of alpha 1-AT. Inhibition of transferrin binding by the acute-phase proteins alpha 1-AT and alpha 2-MG is competitive. Interestingly, inhibition is already present at physiological concentrations. However, full inhibition is only achieved at concentrations above the normal range, which are attained in acute-phase reactions.

Binding Sites↗

Cineradiography for determination of normal and abnormal function in mechanical heart valves.

To determine the diagnostic value of cineradiography of mechanical heart valves, 112 cinefluoroscopic studies were performed in 76 patients with 95 valve prostheses (caged ball or disk valves, tilting disk and bileaflet valves). A patient group (n = 45) presenting with clinical or echocardiographic findings suggestive of valve-related complications was compared with a control group (n = 31) without such symptoms. Disk-opening angles (mean +/- SD) for Medtronic Hall aortic valves were found to be significantly smaller (62.8 +/- 11.1 degrees) in patients than in control subjects (73.9 +/- 1.6 degrees; p < 0.05). Tissue ingrowth or thrombus formation, or both, demonstrated in 3 patients on subsequent reoperation, are considered as the main cause of incomplete or asymmetric disk opening. Opening and closing times did not differ significantly between patients and control subjects. Besides abnormal valve motion, structural defects such as strut fracture or leaflet escape could be rapidly detected by cineradiography if x-ray projections according to the particular valve design were used. Together with quantitative Doppler echocardiographic and clinical data, this method can help to give specific answers if the question is to either confirm or exclude imminent or acute valve malfunction. Thus, modern cineradiography is a highly valuable noninvasive diagnostic tool for both rapid management of emergency cases and routine follow-up of patients with mechanical heart valves.

Aortic Valve↗