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Biomedical subjects

G Otto

Publications and source records attributed to G Otto.

At least 73 records · Page 4Linked to original sources
PubMed1997

Uncoupling of XB/U-cadherin-catenin complex formation from its function in cell-cell adhesion.

Xenopus XB/U-cadherin forms functional complexes with mouse alpha- and beta-catenins and p120(cas) when expressed in murine L-TK- fibroblasts. These cells were stably transfected with cDNAs encoding different cytoplasmic XB/U-cadherin mutants, each partially deleted in the different parts of the 38 most carboxyl-terminal amino acids. The binding of p120(cas) was not affected by carboxyl-terminal deletions, confirming its binding to a region more amino-terminal and distinct from the catenins. alpha- and beta-catenins associate with truncated XB/U-cadherins if either 19 amino acid half of the cadherin 38 amino acid tail is present, indicating that the site of catenin interaction is upstream of the deletions. However, for adhesive function of XB/U-cadherin constructs, the most carboxyl-terminal 19 amino acids are essential; if these amino acids are deleted, cadherin-catenin complexes unable to mediate cell-cell adhesion are formed. Nonadhesive complexes are solubilized by mild detergent, whereas functional complexes are stable. Provided that detergent stability of cadherin-catenin complexes is taken as a measure of their cytoskeletal association, our results give first evidence that cytoskeletal stabilization occurs independent of cadherin-catenin complex formation and requires the 19-amino acid cadherin carboxyl terminus.

Amino Acid Sequence↗
PubMed1997

[Leiomyosarcoma of the inferior vena cava].

HISTORY AND CLINICAL FINDINGS: In a 34-year-old woman who underwent ultrasound investigation because of recurrent pyelonephritis a space-occupying lesion in the liver was an incidental finding. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed a tumour in segment I of the liver. The patient had been on contraceptives for 12 years. She had no symptoms. INVESTIGATIONS: Laboratory tests, including tumour markers, were unremarkable. Diagnostic tests to exclude malignant tumour with metastases were negative (thyroid scintigraphy, mammography, coloscopy and gastroscopy). Further tests (ultrasound, coeliaco-mesentericography, hydro-CT and spiral CT, MRI) revealed a tumour, 5 x 4 x 4 cm, in segment I of the liver, most likely an adenoma. Surgical intervention was indicated by the size and questionable malignancy of the tumor. TREATMENT AND COURSE: At operation a tumour was found which originated from the inferior vena cava (IVC) and displaced segment I of the liver. The tumour was resected and the venous wall reconstructed with a Goretex patch. Histological examination indicated a poorly differentiated leiomyosarcoma of the IVC. Adjuvant radiotherapy was undertaken postoperatively. There has been no evidence of recurrence after 10 months. CONCLUSIONS: Leiomyosarcoma of the IVC can be mistaken, both by ultrasound and tomographic diagnostic procedures, for a tumour in segment I of the liver, especially an adenoma. A leiomyosarcoma of the IVC should be included in the differential diagnosis of an hepatic tumour that lies close to segment I of the liver.

Adenoma↗
PubMed1997

Extrahepatic biliary obstruction impairs microvascular perfusion and increases leukocyte adhesion in rat liver.

To determine if disturbances of the liver microcirculation may be of pathophysiological relevance for liver damage during acute biliary obstruction, we studied the effects of bile duct ligation (BDL) on hepatic microhemodynamics and leukocyte adhesion in rat liver in vivo. Male Wistar rats were subjected to BDL for 3 days and 7 days, respectively. Sham-operated controls underwent laparotomy without BDL. After 3 days, intravital fluorescence microscopy (IVM) and hydrogen gas (H2) clearance were performed to study hepatic microvascular perfusion. Furthermore, leukocyte-endothelial cell interactions were assessed by IVM. Intercellular adhesion molecule 1 (ICAM-1) protein expression was studied by Western blot analysis and tissue immunofluorescence after 3 and 7 days, respectively. Analysis of microvascular perfusion by IVM revealed a marked impairment of sinusoidal perfusion after 3 days. Assessment of H2 clearance confirmed that overall hepatic microvascular perfusion was decreased. In addition, increased leukocyte adhesion in sinusoids and venules could be observed. A concomitant increase of ICAM-1 expression in liver tissue was also noted within the first week after BDL. Our results show that BDL is followed by a marked depression of the hepatic microcirculation and increased leukocyte adhesion in vivo within 3 to 7 days. Together, these findings suggest that deficits in microvascular perfusion and increased neutrophil infiltration may represent a potential source of liver injury during acute biliary obstruction.

Animals↗
PubMed1997

[Significance of diagnostic imaging for determining surgical indications in solid liver tumors].

Radiological imaging is essential for the differential-diagnostic appraisal and the assessment of size, number, and localization of neoplastic liver lesions. The results determine the decision for or against operation and the surgical strategy. Moreover, oncological contraindications against surgery are recognized by imaging procedures. Technical refinements of imaging comprise improved quality of ultrasound and of computed tomography and fast sequences in magnetic resonance imaging. Special investigational protocols and specific contrast agents for ultrasonography and magnetic resonance technique are highly relevant for clinical practice. The value of diagnostic procedures is demonstrated by our own experience. The differential use of imaging procedures, technical and methodological performance and the final diagnostic interpretation require a high standard of expertise. Diagnostic accuracy is limited by technical and biological factors.

Diagnostic Imaging↗
PubMed1997

Human hepatic preneoplasia: phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia.

Foci of altered hepatocytes (FAH) represent preneoplastic lesions, as shown in various animal models of hepatocarcinogenesis, but their significance in the human liver has not been established. The cellular composition, size distribution and proliferation kinetics of FAH in 163 explanted and resected human livers with or without hepatocellular carcinoma (HCC) and their possible association with small-cell change of hepatocytes (SCC) were therefore studied. FAH, including glycogen-storing foci, were found in 84 of 111 cirrhotic livers, demonstrating higher incidences in cases with (29/32) than in those without HCC (55/79). FAH were observed more frequently in HCC-free cirrhosis associated with hepatitis B or C virus or chronic alcoholic abuse (high-risk group) (37/47) than in that due to other causes (low-risk group) (12/21). MCF, predominant in cirrhotic livers of the high-risk group, were more proliferative, larger and more often involved in formation of nodules of altered hepatocytes (39.3%) than were GSF (8.5%). The results suggest that the FAH are preneoplastic lesions, MCF being more advanced than GSF. Oncocytic and amphophilic cell foci were also observed, but their significance remains to be clarified. Two types of SCC, namely diffuse and intrafocal SCC, were identified, but only intrafocal SCC was found to be related to increased proliferative activity and more frequent nodular transformation of the FAH involved, suggesting a close association with progression from FAH to HCC.

Adolescent↗
PubMed1997

Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow.

BACKGROUND: Recent studies provide evidence that nitric oxide (NO) has beneficial effects in hepatic ischemia/reperfusion injury. The purpose of this study was to evaluate whether nitric oxide is involved in the regulation of hepatic microvascular perfusion after warm hepatic ischemia. Therefore, we performed a study using in vivo fluorescence microscopy. METHODS: Clamping of the left liver lobe was performed in male Wistar rats for the duration of 70 min. One experimental group (n=8) received L-NAME (Nw-nitro-L-arginine methyl ester hydrochloride), an NO-synthase inhibitor, 1 min prior to reperfusion. A second experimental group (n=8) received L-arginine (NO-substrate) continuously infused throughout the observation period. Controls (n=8) received equivalent volumes of an isotonic solution and underwent the same procedures. Hepatic microvascular blood flow and leukocyte-endothelial cell interaction was studied between 20 and 90 min after reperfusion using in vivo fluorescence microscopy. RESULTS: Inhibition of NO-synthesis during reperfusion by application of L-NAME caused a marked decrease in sinusoidal blood flow velocity. Furthermore, we noted an increase of non-perfused sinusoids in this group. Treatment with L-arginine improved functional perfusion of hepatic acini and reduced significantly the number of adherent leukocytes in sinusoids and venules compared to control animals. CONCLUSIONS: Our results provide further evidence that NO maintains postischemic hepatic microvascular perfusion and that inhibition of NO synthesis has detrimental effects on hepatic microhemodynamics during reperfusion.

Animals↗
PubMed1997

Effects of mixed ETA and ETB-receptor antagonist (Ro-47-0203) on hepatic microcirculation after warm ischemia.

There is evidence that endothelin (ET) is involved in disturbances of the hepatic microcirculation after warm ischemia. In this study we investigated the influence of a mixed ETA-, ETB-receptor antagonist (Bosentan) on ischemia-reperfusion damage of the liver by means of intravital fluorescence microscopy (IVM). Clamping of the left liver lobe (= warm ischemia) was performed in 16 male Wistar rats for 70 min. The treatment group (N = 8) received 15 mg/kg Bosentan (Ro-47-0203) 1 min prior to reperfusion. Controls (N = 8) received an equivalent amount of Ringer's solution. Between 20 and 90 min after reperfusion, leukocyte-endothelial cell interactions in sinusoids and postsinusoidal venules as well as perfusion of hepatic acini were studied. Application of Bosentan improved sinusoidal blood flow, attenuated manifestations of microvascular perfusion failure, and decreased the number of rolling leukocytes in postsinusoidal venules. Our results provide further evidence that ET is involved in postischemic impairment of hepatic microhemodynamics during reperfusion.

Animals↗
PubMed1997

Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outcome of alcoholism.

The present study was performed to test the hypotheses that allelic variants at the human dopamine D2 receptor gene locus (DRD2) confer susceptibility to alcoholism or are associated with clinical subtypes of alcoholism. We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genotype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls. However, the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addition, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine. Regression analysis revealed the DRD2 E8 genotype as the only significant factor determining withdrawal severity in female alcoholics. The findings suggest an influence of the DRD2 genotype on the neuropharmacological effects of chronic alcohol exposure and the clinical course of alcoholism.

Adaptation, Physiological↗
PubMed1997

Fatal hepatic necrosis after isoflurane anaesthesia.

Several halogenated anaesthetic agents have been associated with hepatotoxicity. We report a case of fulminant, fatal hepatic necrosis after uneventful isoflurane anaesthesia in a patient without previous liver disease, who may have been sensitised by previous exposure to enflurane. Although no anti-trifluoroacetyl antibodies could be detected in the patient's serum, isoflurane hepatotoxicity seems very likely to be the reason for fulminant hepatic failure in this patient.

Adult↗
PubMed1997

Recurrent hepatitis C virus infection after liver transplantation--long-term follow-up with respect to the HCV genotypes/subtypes.

BACKGROUND/AIMS: Various factors may affect the postoperative course in recurrent hepatitis C virus (HCV) infection after liver transplantation (OLT). The aim of our study was to evaluate the potential role of HCV genotypes and immunosuppressive treatment. METHODS: 17 liver allograft recipients, HCV-RNA positive prior to OLT, were followed 26-102 months postoperatively. The diagnosis of HCV infection was based on clinical, serological and histological findings and detectable HCV-RNA in serum. The genotypes/subtypes were evaluated by a "reverse line probe" assay. RESULTS: After OLT hepatitis C viremia was evident in 16 of 17 allograft recipients (94%). Two patients acquired HCV infection after transplantation (incidence 0.84%). Clinically eight of 18 viremic patients remained asymptomatic. Ten of 18 had an acute hepatitis (eleven to 27 weeks after OLT), of those nine patients developed chronic hepatitis (hepatic activity indices: grade 1-3) with progression to fibrosis in two patients. One patient subsequently developed cirrhosis. Subtype 1 b was predominant (eleven of 18 patients). After transplantation subtype 1 b was not associated with a higher rate of recurrent hepatitis compared to other genotypes/subtypes (45% in type 1 b vs. 71% in type "non-1 b"; n.s.). CONCLUSION: Identical HCV genotypes/subtypes before and after OLT indicate a recurrent rather than a postoperatively acquired HCV infection of the allograft. Despite viremia most patients had no or mild to moderate hepatitis in the long-term follow-up. Different HCV genotypes were not associated with specific clinical courses of recurrent HCV infection after OLT.

Adolescent↗
PubMed1997

Prevalence of serum antibodies to Helicobacter pylori and to CagA protein in liver transplant recipients.

OBJECTIVE: To study Helicobacter pylori seroepidemiology before and after orthotopic liver transplantation. METHODS: Serum samples obtained from 118 liver transplant recipients before and after transplantation were examined for the presence of IgG antibodies to H. pylori whole cell extract and to the CagA protein of H. pylori. RESULTS: Of 118 patients, 64 (54.2%) were H. pylori positive, and 36 (56.3%) of these had CagA antibodies. Of the 64 seropositive patients, 22 (34.4%) remained positive and 42 (65.6%) became negative for H. pylori antibodies a median of 39 months after transplantation. Patients who seroreverted showed a tendency to lower pretransplantation antibody levels and had received antibiotic therapy for at least 4 days. Seroreversion or antibody persistence was not affected by age, sex, CagA antibody status, CagA antibody titer, duration of antibiotic therapy, or immunosuppressive drugs administered after liver transplantation. CONCLUSIONS: The prevalence of H. pylori infection, as detected by serological screening, in patients selected for liver transplantation is not different from that in the general population. In these patients, the seroprevalence of H. pylori drops after liver transplantation. This is largely due to the intake of antibiotics and immunosuppressants by transplant recipients. Seroreversion seems to be independent of the type of H. pylori bacteria.

Adult↗
PubMed1997

[Rehabilitation of patients with alcoholic liver cirrhosis after orthotopic liver transplantation: a 7-year follow-up].

Alcoholic liver cirrhosis is the main indication for orthotopic liver transplantation. Since 1988, 52 patients with alcoholic liver cirrhosis have been transplanted at the Department of Surgery of the University of Heidelberg. The survival rates are as follows: 73% of the patients survived for 1 year, 68% for 2 and 3 years, 64% for 4 years, and 57% survived for 5 years. After transplantation, recidivism occurred in 6 patients. Remarkable in this case was the fact that all 6 patients had a relatively short period of abstention prior to surgery (2 to 5 months). In 12 patients, a small carcinoma was found in the cirrhotic liver. This had neither been seen previously by ultrasound nor by computer tomography. In summary, orthotopic liver transplantation is an excellent mode of treatment in end-stage alcoholic liver cirrhosis. However, the patients have to be carefully selected in order to avoid recidivism following transplantation.

Adult↗
PubMed1997

[Prevention of hepatitis B--analysis of cost-effectiveness after liver transplantation].

HBV recurrence, despite immunoprophylaxis which occurred in 67% of our patients, remains the main problem following liver transplantation for HBV infection. Pretransplant viral replication (HBV-DNA) and probably viral mutation may account to some degree for the failures involved in hyperimmunoglobulin prophylaxis. In order to improve the cost/benefit relationship, only HBV-DNA and HBeAG-negative patients should be selected or preoperatively seroconverted by nucleosides (famciclovir, lamivudine); post-operatively a variable HIG prophylaxis should be administered.

2-Aminopurine↗
PubMed1996

Dopamine D2 receptor gene (DRD2) haplotypes in Caucasians.

The human dopamine D2 receptor gene (DRD2) is considered a candidate gene for neuro-psychiatric diseases. We typed three new DNA sequence variants in DRD2 intron 4, intron 6 and exon 8, in combination with the known TaqI A restriction fragment length polymorphism (RFLP) and exon 7 311Ser/Cys in 106 unrelated psychiatrically healthy Caucasians. Based on the genotypic data we delineated 10 distinct DRD2 haplotypes and their genetic relationship. Our data provide evidence that the Taq A1 allele and the 311Cys variant are components of different groups of haplotypes though both variants have been speculated to be associated with alcoholism or schizophrenia in recent studies. Therefore we conclude that the prior knowledge of the frequencies and genetic relationships of DRD2 haplotypes will lead to the selection of more suitable intragenic markers for future association studies.

Gene Frequency↗
PubMed1996

Impact of N-acetylcysteine on the hepatic microcirculation after orthotopic liver transplantation.

Recent observations showed an improvement of hepatic macro- and microhemodynamics as well as survival rates after warm ischemia of the liver following treatment with N-acetylcysteine (NAC). In this study we assessed the influence of NAC on the hepatic microcirculation after orthotopic liver transplantation (OLT) using intravital fluorescence microscopy. OLT with simultaneous arterialization was performed in 16 male Lewis rats following cold storage in University of Wisconsin solution for 24 hr. Within the experimental group (n = 8) donors received NAC (400 mg/kg) 25 min before hepatectomy. In addition, high-dose treatment of recipients with NAC (400 mg/kg) was started with reperfusion. Control animals (n = 8) received an equivalent amount of Ringer's solution. Intravital fluorescence microscopy was performed 30-90 min after reperfusion assessing acinar and sinusoidal perfusion, leukocyte-endothelium interaction, and phagocytic activity. Treatment with NAC reduced the number of nonperfused sinusoid from 52.4 +/- 0.8% to 15.7 +/- 0.5% (p = 0.0001) (mean +/- SEM). Furthermore, we achieved a significant reduction of leukocytes adhering to sinusoidal endothelium (per mm2 liver surface) from 351.9 +/- 13.0 in controls to 83.6 +/- 4.2 in the experimental group (P = 0.0001). In postsinusoidal venules, treatment with NAC decreased the number of sticking leukocytes (per mm2 endothelium) from 1098.5 +/- 59.6 to 425.9 +/- 37.7 (P = 0.0001). Moreover, bile flow was significantly increased after therapy with NAC (4.3 +/- 1.2 vs. 2.2 +/- 0.7 ml/90 min x 100g liver) (P < 0.05). Phagocytic activity was not influenced by application of NAC. We conclude that high-dose therapy with NAC in OLT attenuates manifestations of microvascular perfusion failure early after reperfusion and should be considered as a means to reduce reperfusion injury.

Acetylcysteine↗
PubMed1996

Validation of endothelin (ET) immunoreactivity in human bile by HPLC. Comparison of biliary ET concentration in liver transplant recipients with values obtained during cholecystectomy.

High endothelin (ET) concentrations were recently detected in human bile after orthotopic liver transplantation (OLT). In the present study we compared biliary ET/big-ET levels measured by radioimmunoassay (RIA) in liver graft recipients (n = 37) with levels measured in non-transplant patients during cholecystectomy (n = 38) to clarify the influence of transplantation on the levels of biliary ET peptides. HPLC elution profiles of biliary ET were analyzed for characterization of ET peptide composition and validation of RIA analysis in bile extracts. Mean ET/big-ET levels in the common bile duct after OLT were significantly elevated (ET, 20.9 +/- 15; big-ET, 39.2 +/- 19 fmol/ml) compared to levels in non-transplant patients (ET, 5.7 +/- 4.9; big-ET, 12 +/- 8 fmol/ml). Highest ET/big-ET levels were measured in the gall bladder during cholecystectomy (ET, 61.7 +/- 41; big-ET, 75 +/- 28 fmol/ml). ET and big-ET levels were correlated by linear regression. HPLC analysis reveals the presence of high levels of ET/big-ET in human bile. Biliary ET mostly represents ET-1. High biliary ET levels after OLT appear to be derived from active endothelial secretion and probably reflect hepatic endothelial stress after preservation/ reperfusion. High biliary ET levels could be involved in the mediation of functional cholestatic syndromes after OLT.

Adult↗