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Biomedical subjects

W Vogel

Publications and source records attributed to W Vogel.

At least 289 records · Page 16Linked to original sources

Ion channels in human axons.

1. Until now, no direct electrophysiological information has been available on the molecular basis of human nerve excitability. We here report patch-clamp recordings, both single- and multichannel, from acutely dissociated human axons. 2. Voltage-dependent sodium channels with a conductance gamma = 13 pS (measured in Ringer at room temperature) are found in the nodal area. 3. There are several types of voltage-dependent potassium channels: I channels (gamma = 34 pS), F channels (gamma = 50 pS), and channels with small conductance (gamma = 7-9 pS, all measured in high potassium solution). Most of them are closely similar to those already reported in Xenopus and rat axons; in addition a 200-pS, calcium-dependent potassium channel, similar to that in Xenopus, is present. 4. Differences between the electrical behavior of human axons and those of other species are probably not due to the presence of fundamentally different channel types, but may be due to differences in channel density or distribution. 5. As well as increasing our understanding of the basis of excitability in human nerve, this method may prove useful in the investigation of inherited and other human neuropathies.

Axons↗

Demonstration of replication patterns on histone-depleted chromosomes.

A modified immunologic technique is described for the purpose of demonstrating replication patterns on mammalian chromosomes after partial histone depletion. Replication patterns were induced by BrdU substitution and visualized by BrdU antibodies, coupled with peroxidase (diaminobenzidine/H2O2) or immunogold-detection. The replication patterns obtained by this technique did not reveal any additional details of replication compared to those shown by conventional cytogenetic staining. However, the possibility of demonstrating replication patterns on these partially histone-depleted chromosomes may prove useful for chromosomal in situ hybridization studies since the chromosomes produced are considerably larger than those seen in conventional preparations.

Animals↗

Circulating interleukin-1 and tumor necrosis factor antagonists in liver disease.

The proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor.

Adult↗

A combined biopsy-plugging device based on the Menghini- or Trucut needle for percutaneous liver biopsy: clinical experience.

Impaired blood clotting precludes percutaneous liver biopsy for histologic examination of liver tissue. The transjugular or laparoscopic approach are ways to reduce the risk of bleeding. These techniques, however, are laborious and confined to specialized centers. Methods of plugging the needle track with sealant presented so far are hampered by the need to leave either the cannula in situ or the need for a second percutaneous approach for the application of the sealant. We have tested a combined plugging-biopsy device allowing to perform the biopsy as a one-step procedure in patients with impaired clotting under laparoscopic vision control. In 37 patients either a modified Trucut or Menghini needle was tested. Handling of the Trucut needle proved easier. Tissue yield was satisfactory with both needles. Only one episode of bleeding was observed with a prototype Menghini needle. We conclude, that the combined plugging-biopsy device is a safe and reliable tool for obtaining liver tissue in patients with impaired blood coagulation.

Biopsy, Needle↗

[Therapy of chronic hepatitis B with interferon].

Over the last decade several well conducted studies in Europe and North America have shown that recombinant interferon-alpha (IFN-alpha) is an effective drug for the treatment of chronic hepatitis B. 5 million units given subcutaneously daily or every other day for 4 to 6 months will achieve remission in 30% (complete with loss of all viral markers) to 40% (incomplete with resolution of hepatitis but persistence of viral markers) of patients. High activity of hepatitis and low rate of viral replication are favourable prognostic markers. Male sex, infection in childhood and superinfection with the delta virus are associated with a low response rate. Cirrhotics in particular in the decompensated state of disease should be treated in a center with the possibility of liver transplantation.

Follow-Up Studies↗

Laminin matrix formation and S-100 protein and/or desmin-positive cells in malignant fibrous histiocytoma (MFH).

16/30 human storiform-pleomorphic malignant fibrous histiocytomas (MFH) showed a focal pericellular immunostaining for laminin. 14/16 of these laminin-positive tumours additionally revealed an atypical cellular differentiation (desmin- and/or S-100 protein-positive cells). The significance of focal laminin positivity along with atypical, non-entity specific differentiated cells is discussed before the background of laminin as being an indicator and promoter of differentiation in MFH. The limited value of a laminin detection in MFH for solving differential diagnostic questions (MFH versus other poorly differentiated sarcomas with basement membrane formation) has been pointed out.

Cell Differentiation↗

[After-care by the internal medicine physician following liver transplantation].

Orthotopic liver transplantation offers the only therapeutic option for many patients with end-stage liver disease. In adults, the overall five-year survival following transplantation has increased dramatically from approximately 30% a decade ago to nearly 70% currently. Cyclosporine A became available in the 1970s and substantially improved immunosuppressive therapy. It is now the mainstay of the therapeutic approach to prevent graft rejection. The postoperative care of liver transplant recipients is one of the most exciting challenges in clinical medicine. On the basis of the experience and results of the Innsbruck liver transplant programme the management of liver transplant recipients will be discussed with regard to the typical time frame of complications. We present data of 87 liver transplantations in 84 patients during a 10-year observation period. At present, intraoperative mortality is fortunately close to zero. Most of the deaths occur in the immediate postoperative period. Major complications are haemorrhage, hepatic artery or portal vein thrombosis, biliary leakage or graft dysfunction. In addition, side-effects resulting from high-dose immunosuppressive therapy or from antibiotic and antiviral therapy add to problems in this early period. Opportunistic infections, chronic graft failure, disease recurrence and nephrotoxicity related to Cyclosporine A therapy are complications seen during long-term management of liver transplant patients. The differential diagnosis and the adequate management of these complications are a great challenge to every hepatologist.

Aftercare↗

High prevalence of viral infection in adults with homozygous and heterozygous alpha 1-antitrypsin deficiency and chronic liver disease.

OBJECTIVE: To determine the prevalence of chronic liver disease in adults with homozygous (Pi ZZ) and heterozygous (Pi Z) alpha 1-antitrypsin deficiency and to assess the presence of other possible risk factors for the development of chronic active hepatitis and cirrhosis of the liver in these patients. DESIGN: Cross-sectional study. SETTING: A referral-based university hospital. PATIENTS: Consecutive patients (164) with the Pi ZZ and Pi Z phenotype with and without chronic liver disease. MEASUREMENTS: The presence of antibody to hepatitis C virus (anti-HCV) was determined using an assay incorporating synthetic peptide antigen from capsid protein (United Biomedical [UBI] assay) and a second-generation enzyme immunoassay (Abbott test); the presence of antibody to hepatitis B virus (anti-HBV) was determined using radioimmunoassays incorporating hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg); assays for antinuclear antibody and antimitochondrial antibody (M2 subtype) were also done, and alcohol abuse was assessed by history. RESULTS: Among patients with cirrhosis (32%), 62% were anti-HCV positive by the Abbott test (P = 0.006), and 41% were anti-HCV positive by the UBI assay (P = 0.007). Thirty-three percent of patients with cirrhosis had hepatitis B virus (HBV) infection (P = 0.01); 41% had a history of alcoholism; and 12% had features of autoimmune liver disease. Only five patients (9%) with cirrhosis had no other risk factor for chronic liver disease. Among patients with chronic active hepatitis (7%), 80% were anti-HCV positive by the Abbott test (P = 0.002), and 75% were anti-HCV positive by the UBI assay (P less than 0.001). Thirty percent of patients with chronic active hepatitis had HBV infection (P = 0.023); 18% had autoimmune hepatitis; and 8% abused alcohol. Only two patients (17%) had no additional risk factor for the development of chronic active hepatitis. Among patients with steatosis of the liver (48%), 5% were anti-HCV positive by the Abbott test, and none were anti-HCV positive by the UBI assay; 18% had serologic evidence of past HBV infection, and 28% abused alcohol. Among patients without chronic liver disease (13%), no viral infection could be found; 9% were alcoholics. CONCLUSIONS: Chronic liver disease in patients with alpha 1-antitrypsin deficiency is associated with a high prevalence of viral infection; this infection, rather than alpha 1-antitrypsin deficiency alone, may be the cause of the liver disease in such patients.

Adolescent↗

Expression of RPS4X in fibroblasts from patients with structural aberrations of the X chromosome.

A series of fibroblasts from patients with numerical or structural aberrations of the X chromosome were scored for the amount of mRNA of ribosomal protein S4 (RPS4X). Haplo-insufficiency of this gene has been reported previously to be a possible cause of Turner syndrome. Our results show that the transcription rate of RPS4X correlates with the number of gene copies. This confirms earlier findings indicating that this gene escapes X inactivation. In addition, we demonstrate that this applies to structurally aberrant X chromosomes. Our results show that RPS4X does not give rise to a type of haplo-insufficiency in these cases, because it escapes inactivation, even on structurally aberrant X chromosomes from patients with Turner syndrome. We therefore assume that RPS4X is not the most prominent candidate gene for Turner syndrome.

Base Sequence↗

A TEA-insensitive flickering potassium channel active around the resting potential in myelinated nerve.

A novel potassium-selective channel which is active at membrane potentials between -100 mV and +40 mV has been identified in peripheral myelinated axons of Xenopus laevis using the patch-clamp technique. At negative potentials with 105 mM-K on both sides of the membrane, the channel at 1 kHz resolution showed a series of brief openings and closings interrupted by longer closings, resulting in a flickery bursting activity. Measurements with resolution up to 10 kHz revealed a single-channel conductance of 49 pS with 105 mM-K and 17 pS with 2.5 mM-K on the outer side of the membrane. The channel was selective for K ions over Na ions (PNa/PK = 0.033). The probability of being within a burst in outside-out patches varied from patch to patch (> 0.2, but often > 0.9), and was independent of membrane potential. Open-time histograms were satisfactorily described with a single exponential (tau o = 0.09 msec), closed times with the sum of three exponentials (tau c = 0.13, 5.9, and 36.6 msec). Sensitivity to external tetraethylammonium was comparatively low (IC50 = 19.0 mM). External Cs ions reduced the apparent unitary conductance for inward currents at Em = -90 mV (IC50 = 1.1 mM). Ba and, more potently, Zn ions lowered not only the apparent single-channel conductance but also open probability. The local anesthetic bupivacaine with high potency reduced probability of being within a burst (IC50 = 165 nM). The flickering K channel is clearly different from the other five types of K channels identified so far in the same preparation. We suggest that this channel may form the molecular basis of the resting potential in vertebrate myelinated axons.

Animals↗

Demonstration of replication patterns in the last premeiotic S-phase of male Chinese hamsters after BrdU pulse labeling.

Chromosome replication in the last premeiotic S-phase of male mammals has been previously studied by [3H]thymidine autoradiography and by a 5-bromodeoxyuridine (BrdU)/Giemsa technique. We used a recently developed BrdU-antibody technique (BAT) in this study. The following conclusions were drawn: (1) The replication patterns observed are similar to that of somatic cells. (2) The heterochromatin starts replication in early S-phase. (3) The euchromatic part of the X chromosome of the male Chinese hamster replicates together with the autosomes and therefore behaves isocyclicly and not allocyclicly as hitherto assumed. Hence, genetic inactivity of the X chromosome may be brought about by a mechanism different from that in somatic cells.

Animals↗

Successful treatment of recurrent hepatic Candida infection with fluconazole after chemotherapy for acute leukemia: a case report.

Hepatic candidiasis represents an increasingly difficult problem in immunocompromised patients. It has been recognized as a variant of disseminated candidiasis after a period of neutropenia. Establishment of diagnosis is difficult since liver biopsy as well as culture may be negative, in spite of the presence of fungus. Hepatic lesions are generally not detectable by ultrasound examination or computed tomography until the neutrophil count has returned to normal. The aim of this case report is to describe the problems related to the diagnosis and treatment of hepatic candidiasis following chemotherapy for acute leukemia. The report also provides further evidence that fluconazole, a new broad-spectrum antifungal drug, can be safely and effectively used for the long-term treatment of deep-seated hepatic candidiasis.

Adult↗

Hepatocellular transplantation into the lung for temporary support of acute liver failure in the rat.

Because hepatocyte transplantation into the spleen or the peritoneal cavity, although successful in rats, is more difficult and less successful in larger animals, the lung was chosen for its accessibility and its high oxygen content as a new site for hepatocyte implantation for treatment of acute hepatic failure. Acute hepatic failure was induced by a combination by a portocaval side-to-side shunt and an 80% liver resection, which was associated with a greater than 90% mortality. Hepatocyte transplantation was performed either by injection of 1 x 10(7) cells via the jugular vein (100% mortality) or 5-7 x 10(7) cells transcutaneously into the right lung (92% survival). After injection of the cell-free supernatant into the lung, 53.3% of the animals survived. If more than 90% of the liver was resected, none of the animals survived despite hepatocyte or supernatant injection. From these findings, it is concluded that the lung is a suitable home for hepatocytes. However, the hepatocytes survived only in cases of acute hepatic failure with some remaining vital liver parenchyma.

Acute Disease↗

Serum levels of cytokines in chronic liver diseases.

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and C-reactive protein (CRP) were investigated in patients with chronic liver diseases (CLD) and correlated with the type of underlying disease and various clinical and laboratory parameters. Two hundred sixty-four patients suffering from various CLD were studied; 136 cases presented with liver cirrhosis, and 128 patients were in the noncirrhotic stage of their underlying liver diseases. Serum levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and CRP were elevated in patients with CLD. Endogenous cytokine patterns in CLD were stage dependent and only marginally affected by the type of underlying disease. The cirrhotic group of CLD patients showed higher serum levels in IL-1 beta, IL-6, TNF-alpha, and CRP than did noncirrhotic cases, and these differences reached the level of statistical significance. IL-1 beta and TNF-alpha values were closely correlated but did not correlate with IL-6 levels. Elevated concentrations of cytokines represent a characteristic feature of CLD regardless of underlying disease. This and the apparent stage-dependency suggest that enhanced endogenous cytokine levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Adolescent↗