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Biomedical subjects

S Zeuzem

Publications and source records attributed to S Zeuzem.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Generalized hyperpigmentation and malignant acanthosis nigricans. A case of a patient with hereditary hemochromatosis and gastric cancer].

A 56-year-old previously healthy man developed hyperpigmentation of the entire skin over the previous 6 months without any other signs of further impairment. Additionally, we found accentuated skin lines of the neck and intertriginous sites as well as cutaneous papillomatosis. Histological examinations, laboratory tests and technical diagnostics revealed the existence of both hereditary hemochromatosis and adenocarcinoma of the stomach. Simultaneous manifestation of hyperpigmentation as a result of hemochromatosis as well as malignant acanthosis nigricans as a paraneoplastic symptom in gastric cancer is very rare.

Acanthosis Nigricans↗
PubMed2005

Development of ulcerative colitis after heart transplantation during immunosuppressive therapy.

BACKGROUND: Cardiac transplantation has become an accepted treatment modality for end-stage heart failure. Immunosuppressive agents, which are used after transplantation, are considered as therapeutic options for inflammatory bowel disease. CASE REPORT: We report on a 53-year-old patient who was treated for 2 years with cyclosporine A, azathioprine and prednisolone after heart transplantation. He developed a distal colitis with all features of ulcerative colitis. An infectious or ischemic etiology was carefully excluded. In spite of high-dose treatment with prednisolone the patient's abdominal symptoms worsened and he developed a progression of the inflammation in the entire colon and a colectomy with ileostomy was necessary. The histology was consistent with ulcerative colitis. After colectomy he recovered and remained in a good state of health. CONCLUSIONS: This report supports the concept that new onset inflammatory bowel disease can develop in a heart transplantation recipient in spite of immunosuppression.

Biopsy↗
PubMed2005

Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C.

In patients with chronic hepatitis C, alanine aminotransferase (ALT) levels do not accurately reflect the extent of liver inflammation. The discrepancy between ALT level and liver damage could be related to the mode of cell death. In the present study, we quantified serum levels of apoptotic cytokeratin 18 (CK-18) neoepitopes that are generated by activated caspases during apoptosis. Apoptotic CK-18 neoepitopes were quantified by enzyme linked immunosorbent assay in sera from patients with chronic hepatitis C and elevated ALT levels (n = 72), patients with chronic hepatitis C and persistently normal ALT levels (n = 27) and healthy controls (n = 19). Serum CK-18 neoepitope levels were strongly correlated with ALT (r = 0.659, P < 0.0001) and the histology activity index (r = 0.374, P < 0.001). Patients with chronic hepatitis C and persistently normal ALT levels had higher apoptotic CK-18 neoepitope levels than healthy controls (P = 0.03) but lower levels than patients with chronic hepatitis C and elevated ALT levels (P < 0.001). Highest serum CK-18 neoepitope levels were observed in patients with cirrhosis (P = 0.002). Hence apoptotic CK-18 neoepitopes in serum of patients with chronic hepatitis C are associated with ALT level and histological liver damage. Serum apoptotic CK-18 neoepitope levels are elevated both in patients with chronic hepatitis C and elevated ALT levels as well as in patients with normal ALT levels indicating that also patients with chronic hepatitis C and normal ALT have an increased hepatocyte loss by apoptosis.

Adult↗
PubMed2004

Antioxidative treatment prevents activation of death-receptor- and mitochondrion-dependent apoptosis in the hearts of diabetic rats.

AIMS/HYPOTHESIS: The mechanisms by which glucose injures cells of the cardiovascular system include generation of reactive oxygen species and induction of cellular apoptosis. To date, little is known about the molecular events of hyperglycaemia-induced apoptosis in the heart in vivo. METHODS: Male Sprague-Dawley rats were rendered diabetic by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin. Caspase activities in cardiac ventricular tissue were determined using fluorometric and immunoassay caspase-activity assay kits respectively. Expression levels of proteins of the apoptotic cascade were determined with western blot analyses using specific antibodies. RESULTS: Four weeks of hyperglycaemia induced significant apoptosis in cardiac tissue. Determining the initiators of death-receptor-dependent apoptosis revealed induction of CD95/Fas and caspase-8. Examination of the activities of effector caspases revealed increased activity of caspase-6, but not caspase-3 and -7. On evaluating inhibitors of apoptosis, we found up-regulation of caspase-3 and -7-inhibiting X-linked inhibitors of apoptosis in diabetic rats. Hyperglycaemia also induced significant mitochondrion-dependent apoptosis. Our evaluation of expression levels of Bcl-2 family members showed increased expression of pro-apoptotic Bak and Bax in diabetic rats. Antioxidative treatment with lipoic acid significantly suppressed apoptosis and down-regulated caspase-6, -8 and -9 activity, as well as expression levels of pro-apoptotic Bcl-2 proteins without changing blood glucose levels. CONCLUSIONS/INTERPRETATION: The present study indicates that reactive oxygen species induced by high glucose are involved in both death-receptor- and mitochondrion-dependent apoptosis in the heart in vivo. It also suggests that antioxidants may be a therapeutic option for preventing cardiovascular damage in diabetes mellitus in humans.

Animals↗
PubMed2004

[Postexposure prevention after occupational exposure to HBV, HCV and HIV].

After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.

Drug Therapy, Combination↗
PubMed2004

[Postexposure prophylaxis after occupational exposure to HBV, HCV and HIV].

After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.

Acute Disease↗
PubMed2004

[Post-exposure prevention after occupational exposure to HBV, HCV and HIV].

After occupational exposure to HBV, HCV, and HIV, the patient from whom the potentially infectious material originates (index patient) as well as the exposed person should undergo serological and, if needed, molecular screening. Active and passive immunoprophylaxis after exposure to HBV is an effective tool against infection with hepatitis B virus in unvaccinated persons. The post-exposure prophylaxis (PEP) should be given within 24 h after exposure of an unprotected person to HBV-positive material. Once acute hepatitis B infection is diagnosed, therapy is not recommended for immunocompetent persons. At present, PEP against HCV infection is not available. Monotherapy with interferon-alpha avoids chronification in most patients suffering from acute hepatitis C. After exposure with an increased risk for transmission of HIV (percutaneous needle stick injury, cut), PEP should be recommended and can also be offered for further indications. PEP should be started as early as possible and carried out for 28 days. The recommended PEP consists of two inhibitors of the reverse transcriptase and one inhibitor of the protease.

HIV Infections↗
PubMed2004

Duodenal angiolipoma -- endoscopic diagnosis and therapy.

We report on two patients with upper gastrointestinal bleeding owing to duodenal angiolipomas, and their endoscopic diagnosis and therapy. In both cases the bleeding source was a pedunculated tumour. Diagnosis and definitive therapy was made by endoscopic snare polypectomy. After stopping the bleeding from the mucosal defect by injection therapy in one patient, the further course was uneventful in both. A colonic angiolipoma in one of the patients was also treated by polypectomy. Gastrointestinal angiolipomas are exceedingly rare, however, these case reports show that duodenal angiolipomas do exist and that they, as lipomas, may lead to substantial gastrointestinal bleeding and may be treated successfully by standard polypectomy techniques.

Adenomatous Polyps↗
PubMed2004

Mutations in the putative HCV-E2 CD81 binding regions and correlation with cell surface CD81 expression.

The hepatitis C virus (HCV) envelope (E)2 protein interacts with the cellular receptor CD81 leading to modulation of B and T cell function. Recently, a higher binding affinity of subtype 1a in comparison with 1b derived E2 proteins for CD81 in vitro was described. The importance of mutations within the putative CD81 binding regions of different HCV geno-/subtypes in correlation with CD81 expression is unknown. In the present study, CD81 expression on blood lymphocytes of patients with chronic hepatitis C infected with different HCV geno-/subtypes were analysed by fluorescence activated cell sorter analyses. In addition, the putative CD81 binding regions on the E2 gene comprising the hypervariable region (HVR)2 were analysed by direct sequencing. CD81 expression on CD8(+) T-lymphocytes from patients infected with subtype 1a (n = 6) was significantly higher in comparison with subtype 1b (n = 12) and 3 (n = 5) infected patients before and during antiviral therapy (P = 0.006; P = 0.021, respectively). Sequencing of the putative CD81 binding regions in the E2 protein comprising the HVR2 (codon 474-495 and 522-552 according to the HCV-1a prototype HCV-H) showed a highly conserved motif within HVR2 for subtype 1a isolates and an overall low number of mutations within the putative CD81 binding regions, whereas numerous mutations were detected for subtype 1b isolates (12.0 vs 23.6%). HCV-3 isolates showed an intermediate number of mutations within the putative binding sites (19.2%; P = 0.022). In conclusion, the highly conserved sequence within HVR2 and putative CD81 binding sites of subtype 1a isolates previously associated with a high CD81 binding affinity in vitro is correlated with high CD81 expression on CD8(+) T-lymphocytes in vivo.

Adult↗
PubMed2004

An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn's disease and experimental colitis in vivo.

BACKGROUND AND AIMS: Interleukin-12 (IL-12), a p35/p40 heterodimer, plays a pivotal role in the immune response in Crohn's disease (CD). Since IL-12 p40 dimers act as IL-12 antagonists, we assayed p40 dimer proteins to modulate chronic intestinal inflammation. METHODS: We generated a fusion protein consisting of the IL-12(p40) subunit fused to the constant region of IgG2b. IL-12(p40)-IgG2b was tested in a murine 2,4,6,-trinitrobenzene sulphonic acid (TNBS) colitis model and in lamina propria mononuclear cells (LPMNC) from patients with CD in vitro. RESULTS: Dimeric IL-12(p40)-IgG2b fusion protein bound specifically to the IL-12 receptor. In concentrations <10(-7) M, it acted as an IL-12 antagonist as it inhibited interferon gamma (IFN-gamma) secretion, suppressed proliferation, and increased apoptosis of LPMNC from patients with CD. However, in concentrations >10(-6) M, IL-12(p40)-IgG2b increased IFN-gamma secretion and lymphocyte proliferation thereby acting as an IL-12 agonist. In TNBS colitic mice, IL-12(p40)-IgG2b decreased mortality (10% v 68%), prevented body weight loss, reduced tumour necrosis factor alpha, and increased IL-10 secretion. CONCLUSIONS: The IL-12(p40)-IgG2b fusion protein has dichotomic properties as a specific IL-12 antagonist and selective repressor of mucosal inflammation at low concentration and as an IL-12 agonist at high concentration.

Adult↗
PubMed2004

Receptor tyrosine kinases are signaling intermediates of G protein-coupled receptors.

G protein-coupled receptors (GPCRs) can utilize receptor tyrosine kinases (RTKs) to mediate important cellular responses such as proliferation, differentiation and survival. Recent advances in the field suggest that GPCR-induced transactivation of RTKs might be important for diseases such as cancer and cardiac hypertrophy. Depending on the receptor and cell type, GPCR signaling involves activation of several different RTKs. By activating different subsets of RTKs, GPCRs can fine-tune their effects on target cells. Furthermore, RTK-independent signaling pathways also initiated by GPCRs may modify the biological read out of the transactivated RTKs. This review focuses on the mechanisms how GPCRs and intracellular messengers elicit transactivation of different RTKs and the resulting different biological responses.

Cell Communication↗
PubMed2003

[44-year-old patient with fulminant liver failure].

The 44-year old female patient was admitted with acute hepatic failure and extensive haemolysis under the preliminary diagnosis of Wilson's disease. General characteristic criteria of Wilson's disease as Kayser-Fleischer ring, low serum copper and low ceruloplasmin levels were not observed. The preliminary diagnosis of acute Wilson's disease was established on the basis of the characteristic laboratory values with an AP/bilirubin ratio <2, an AST/ALT ratio >4, accompanying hemolysis and a highly elevated cupruresis. The definitive diagnosis of Wilson's disease was verified after orthotopic liver transplantation by quantitative copper evaluation in the explanted liver. The case represents the yet oldest patient reported with an acute manifestation of Wilson's disease.

Adult↗