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Biomedical subjects

W Vogel

Publications and source records attributed to W Vogel.

At least 199 records · Page 11Linked to original sources

Myasthenia gravis and primary biliary cirrhosis. Common immunological features and rare coincidence.

A 43-year-old woman with recently diagnosed primary biliary cirrhosis developed antibody-negative myasthenia gravis. She did not receive D-penicillamine therapy. Clinical and immunological features of this patient are discussed. In previous reports on an association between primary biliary cirrhosis and myasthenia D-penicillamine treatment was an obligate causal linkage between both disorders.

Adult↗

Simultaneous transplantation of isolated hepatocytes reduces rejection of small bowel allografts and improves survival in the rat.

Hepatocytes transplanted some days prior to vascularized allografts were shown to have the potential to prolong allograft survival in the rat. In the present study, hepatocytes and small bowel allografts were transplanted simultaneously in a Lewis (donor)-Brown Norway (recipient) rat model. 8-15 x 10(6) liver cells were injected into the spleen of small bowel recipients. The administration of at least 10 mg cyclosporine A (CyA)/kg over 3 days was necessary to prevent early rejection of hepatocytes. In groups simultaneously receiving hepatocytes, small bowel grafts and 10 mg CyA/kg over 3 days, a significant mitigation of rejection and a prolongation of survival was achieved, compared to groups receiving solely small bowel grafts and 10 mg CyA/kg over 3 days. We conclude that simultaneously transplanted hepatocytes exert a protective effect on a grafted organ from the same donor, provided that early rejection of hepatocytes is prevented by sufficient immunosuppression.

Animals↗

A survey of physician use of treatment methods for functional enuresis.

We report a survey of treatment methods used by primary care physicians in Worcester, Massachusetts in the treatment of functional enuresis. The results suggest a predominance in the use of psychobehavioral over pharmacologic treatment methods and are in contrast to previous studies. Ninety-one percent of physicians reported recommending the use of rewards to control enuresis. Eighty percent of physicians reported using the "bell-and-pad" conditioning method for treatment of functional nocturnal enuresis, contrasted with 5% of physicians reported in previous studies. Fifty-two percent of physicians reported using medication for treatment of functional nocturnal enuresis, despite substantial evidence of its dubious efficacy.

Attitude of Health Personnel↗

Unusual thoracic collaterals of gastro-oesophageal varices in a patient with end-stage liver disease.

Thoracic varices are rare anomalies in patients with liver cirrhosis and portal hypertension. Gastro-oesophageal varices usually drain into the azygos or hemiazygos vein. The case is reported here of an unusual collateral pathway of gastro-oesophageal varices with drainage to the vena anonyma system presenting as lung masses on chest X-ray, which completely resolved after successful liver transplantation.

Collateral Circulation↗

Acute renal failure complicating non-fulminant hepatitis A.

Hepatitis, A is usually a mild and self-limiting infection of the liver. Whereas the clinical course is usually benign in children, complications such as prolonged cholestasis and fulminant liver failure have been reported in adults. Acute functional renal failure is an uncommon event in the absence of fulminating liver disease. So far, only cases of acute hepatitis A with biopsy-proven interstitial renal disease or tubular necrosis have been reported [Geltner et al. 1992. Kramer et al. 1986]. We present the case of a 35-year-old, previously healthy male with non-fulminant cholestatic viral hepatitis A, who developed progressive oliguric renal failure requiring dialysis therapy. Kidney biopsy ruled out glomerular disease and tubular necrosis. In the absence of bleeding and other causes of fluid depletion this case may be another variant of hepatorenal syndrome whose etiopathogenesis is only poorly understood.

Acute Kidney Injury↗

Multiple in vivo phosphorylated tyrosine phosphatase SHP-2 engages binding to Grb2 via tyrosine 584.

SHP-2 (also named PTP1D, syp, or SH-PTP2) has been identified as a phosphotyrosine phosphatase comprising two src-homology-2 (SH2) domains. Upon growth factor stimulation, SHP-2 becomes tyrosine phosphorylated, thereby increasing its catalytic activity. Here, we identified SHP-2 to be phosphorylated on multiple tyrosine residues in response to different stimuli and unmasked the carboxyl-terminal tyrosine 584 as a major phosphorylation site in human cell lines. Tyrosine 584 shares, together with tyrosine 546, the consensus sequence pY-X-N-X, a characteristic of potential binding sites for the SH2 domain of growth factor receptor-bound protein 2 (Grb2). We show here that mutation of tyrosine 584, but not tyrosine 546, to phenylalanine totally abolished the binding of Grb2 to SHP-2. By using a systematic mutagenesis approach, phosphorylation of additional tyrosines in each of the SH2 domains of SHP-2 was detected after coexpression of epidermal growth factor receptor, but not after coexpression of platelet-derived growth factor receptor, whereas tyrosine 263 located in the interspace between SH2 and catalytic domain appears to be exclusively recognized by platelet-derived growth factor receptor. Immunoprecipitation of SHP-2 from a panel of mammary carcinoma cell lines copurifies several tyrosine phosphorylated proteins; the most prominent band has an apparent molecular weight of M(r) 115,000.

Adaptor Proteins, Signal Transducing↗

[Hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The profile of risk factors associated with HCC includes not only chronic infection with hepatitis B virus and/or hepatitis C virus with subsequent cirrhosis, but also metabolic and alcoholic chronic liver diseases. While the risk of developing cancer is high in patients with cirrhosis, the aim of most screening programmes is to detect small, potentially resectable tumors. Serum alpha 1-fetoprotein lacks both sensitivity and specificity as a screening test and two-thirds of patients with small HCCs have levels below 200 ng/ml. Hepatic resection or liver transplantation at an early stage of HCC, without extrahepatic metastasis, provide complete cure of the disease.

Adult↗

Protein-tyrosine phosphatase 1D modulates its own state of tyrosine phosphorylation.

The insulin receptor-mediated signal transduction pathway involves insulin receptor substrate 1 and a variety of proteins containing Src homology-2 (SH2) domains, such as phosphatidylinositol 3-kinase, Grb2, and protein-tyrosine phosphatase 1D (PTP1D). Upon insulin stimulation of baby hamster kidney cells overexpressing the IR, the catalytically inactive mutant of PTP1D, C463A, becomes tyrosine-phosphorylated and coprecipitates with Grb2. Tyrosine phosphorylation of this mutant is significantly reduced when wild type PTP1D is coexpressed. Substitution of tyrosine residues 546 and 584 with phenylalanine abrogates tyrosine phosphorylation of the catalytically inactive mutant and abolishes its interaction with Grb2.

Animals↗

Single voltage-activated Na+ and K+ channels in the somata of rat motoneurones.

1. Voltage-activated Na+ and K+ channels were investigated in the soma membrane of motoneurones using the patch-clamp technique applied to thin slices of neonatal rat spinal cord. 2. One type of TTX-sensitive Na+ channel, with a conductance of 14.0 pS, was found to underlie the macroscopic Na+ conductance in the somata of motoneurones. These channels activated within a potential range between -60 and -20 mV with a potential of half-maximal activation (E50) of -38.9 mV and steepness factor (k) of 6.1 mV. 3. Kinetics of Na+ channel inactivation could be fitted with a single exponential function at all potentials investigated. The curve of the steady-state inactivation had the following parameters: a half-maximal potential (Eh,50) of -81.6 mV and k of -10.2 mV. 4. Kinetics of recovery of Na+ channels from inactivation at a potential of -80 mV were double exponential with fast and slow components of 16.2 (76%) and 153.7 ms (24%), respectively. It is suggested that the recovery of Na+ channels from inactivation plays a major role in defining the limiting firing frequency of action potentials in motoneurones. 5. Whole-cell K+ currents consisted of transient (A)- and delayed-rectifier (DR)-components. The A-component activated between -60 and +20 mV with an E50 of -33.3 mV and k of 15.7 mV. The curve of steady-state inactivation was best fitted with an Eh,50 of -82.5 mV and k of -10.2 mV. The DR-component of K+ current activated smoothly at more positive potentials. E50 and k for DR-currents were +1.4 and 16.9 mV, respectively. 6. The most frequent single K+ channel found in the somata of motoneurones was the fast inactivating A-channel with a conductance of 19.2 pS in external Ringer solution. In symmetrical high-K+ solutions the conductance was 50.9 and 39.6 pS for inward and outward currents, respectively. The channel activation took place between -60 and +20 mV. The curve of steady-state inactivation of single A-channels had an Eh,50 of -87.1 mV and k of -12.8 mV. In high-Ko+ solution A-channels demonstrated a rapid deactivation at potentials between -110 and -60 mV. The time constant of the channel deactivation depended on the membrane potential and changed from 1.5 ms at -110 mV to 6.3 ms at -60 mV. 7. Delayed-rectifier K+ channels were found in the soma membrane at a moderate density.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗