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G Otto

Publications and source records attributed to G Otto.

At least 37 records · Page 2Linked to original sources
PubMed1999

CDKN2 mutation is infrequent in german hepatocellular carcinoma.

For hepatocellular carcinoma, only scarce and controversial data on CDKN2 alterations are available. A high rate of mutations in a Chinese study contrasts with a low rate found in Japanese tumors and a CDKN2 germline mutation in 4/26 Swiss tumors examined. We analyzed 23 hepatocellular carcinomas from German patients for homozygous deletions of CDKN2 by coamplification with the human tyrosine hydroxylase (TH) gene and for CDKN2 mutations by PCR-single strand conformation polymorphism analysis and direct DNA sequencing. Our results indicate the lack of homozygous deletions. In one tumor, DNA sequencing showed a GCG-ACG (alanine-threonine) substitution at codon 148, a polymorphism in exon 2 of CDKN2. We conclude that the alteration of CDKN2 by deletion or mutation appears not to be a frequent event in hepatocarcinogenesis in German patients.

Adolescent↗
PubMed1999

Effect of anesthesia on a whole blood lymphocyte proliferation assay in the rat.

Lymphocyte proliferation assays are commonly used to quantify the effects of immunosuppressive drugs in animal models, but the influence of anesthetic agents on those assays is not well understood. We used a whole blood proliferation assay to compare lymphocyte proliferation in blood drawn from normal male Lewis rats that were sedated using three common methods. Rats (n = 12) were serially bled from the orbital plexus while anesthetized with diethyl ether, methoxyflurane, or carbon dioxide. Before the beginning of the anesthetic trials, a random subset of the rats (n = 6) was bled via the jugular vein using only manual restraint to provide a baseline control group. A comparison of the lymphocyte proliferation results obtained under these four conditions (manual restraint, diethyl ether, methoxyflurane, or CO2) showed no significant differences. The only hematological variation seen was an elevation of the number of circulating lymphocytes when ether was used. We conclude that there is no justification for withholding sedation when bleeding rats for this type of lymphocyte proliferation. Furthermore, when considering the use of one of the agents examined in this study, the method can be chosen based on factors other than potential adverse effects on the assay results.

Anesthetics↗
PubMed1998

Complement inhibition by soluble complement receptor type 1 improves microcirculation after rat liver transplantation.

BACKGROUND: Recent observations provide evidence that complement is involved in the pathophysiology of ischemia/reperfusion injury. In this study, we assessed the impact of complement inhibition on hepatic microcirculation and graft function using a rat model of liver transplantation. METHODS: Arterialized orthotopic liver transplantation was performed in Lewis rats after cold preservation (University of Wisconsin solution, 4 degrees C, 24 h). Eight animals received the physiological complement regulator soluble complement receptor type 1 (sCR1) intravenously 1 min before reperfusion. Controls received Ringer's solution (n=8). Microvascular perfusion, leukocyte adhesion, and Kupffer cell phagocytic activity were studied 30-100 min after reperfusion by in vivo microscopy. RESULTS: Microvascular perfusion in hepatic sinusoids was improved in the sCR1 group (87+/-0.7% vs. 50+/-1%; P < 0.001). The number of adherent leukocytes was reduced in sinusoids (68.3+/-4.7 vs. 334.1+/-15.8 [adherent leukocytes per mm < or = liver surface]; P < 0.001) and in postsinusoidal venules after sCR1 treatment (306.6+/-21.8 vs. 931.6+/-55.9 [adherent leukocytes per mm < or = endothelial surface]; P < 0.001). Kupffer cell phagocytic activity was decreased in the sCR1 group compared to controls. Postischemic bile production reflecting hepatocellular function was increased by almost 200% (P = 0.004) after complement inhibition. Plasmatic liver enzyme activity was decreased significantly upon sCR1 treatment, indicating reduced parenchymal cell injury. CONCLUSIONS: Our results provide further evidence that the complement system plays a decisive role in hepatic ischemia/reperfusion injury. We conclude that complement inhibition by sCR1 represents an effective treatment to prevent reperfusion injury in liver transplantation.

Animals↗
PubMed1998

Differential immunosuppressive activity of monoclonal CD2 antibodies on allograft rejection versus specific antibody production.

CD2 is a co-stimulatory receptor involved in T cell activation. Here we report on immunosuppressive effects of three mouse CD2 monoclonal antibodies (OX34, OX54, OX55) directed against non-overlapping epitopes of the rat CD2 receptor on various modes of T cell activation in vitro and in vivo. Although non-ligand-blocking OX54 and OX55, in concert, activated T cells through CD2 in vitro, they individually suppressed the mixed lymphocyte reaction (MLR) and significantly prolonged allograft survival after rat heart transplantation in vivo. Phenotype analysis revealed that OX55 significantly down-modulated CD2 in vivo, whereas OX54 depleted T cells. Graft rejection coincided with re-expression of CD2 and clearance of OX55 from serum, whereas T cell depletion by OX54 outlasted the period of graft survival. The most suppressive antibody, OX34, down-modulated CD2 and inhibited T cell activation through the TCR or CD2 and the MLR and prolonged median allograft survival time from 7 days in controls to 45 days in the absence of any additional treatment. Graft survival was clearly dose dependent and correlated with the duration of CD2 down-modulation and the presence of circulating CD2 antibody in serum. Importantly, the specific antibody production to a T cell-dependent antigen as demonstrated by immunization with keyhole limpet hemocyanin in vivo remained unaffected after treatment with OX34. These results demonstrate the pivotal role of CD2 signaling in mediating allogeneic immune reactions after vascularized organ transplantation while allowing specific humoral immune responses in vivo.

Animals↗
PubMed1998

Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas.

Transactivation of cellular genes and functional inactivation of p53 by the hepatitis B virus (HBV) X gene-encoded protein (HBx) are proposed as alternative mechanisms for induction of hepatocellular carcinomas (HCCs) in chronic HBV infection. Using an immunohistochemical approach, we studied the expression of HBx in 39 explanted livers with HBV-associated disease. Because the data reported previously have been inconsistent, possibly due to the application of different antibodies, we compared results with 5 polyclonal and 6 monoclonal anti-HBx antibodies from five laboratories. Ten of the 11 antibodies reacted with recombinant HBx by Western blotting, but only 1 polyclonal and 2 monoclonal antibodies reacted specifically with HBx in tissue, and were thus suitable for immunohistochemistry. Three other polyclonal antibodies reacted with tissue components in addition to HBx. One polyclonal and 4 monoclonal antibodies did not recognize the HBx in the tissue. HBx was demonstrated in 16 of 30 (53.3%) cirrhotic livers and 10 of 18 (58.8%) HCCs by all specific antibodies. The expression of HBx, among three HBV antigens examined, was found to be preferentially maintained in HCC and the surrounding liver parenchyma, including focal or nodular preneoplastic lesions. However, the immunoreactivity was always limited to the cytoplasm of a small number of parenchymal and neoplastic cells. The role of X gene expression in HBV-associated human hepatocarcinogenesis remains to be established.

Animals↗
PubMed1998

Cytokeratin expression is reduced in glycogenotic clear hepatocytes but increased in ground-glass cells in chronic human and woodchuck hepadnaviral infection.

Hepatocytes of normal adult liver express cytokeratins (CKs) 8/18, but bile duct cells additionally contain CK7/19. We have previously demonstrated the frequent occurrence of foci of altered hepatocytes in association with hepatic tumors in humans and provided evidence for a preneoplastic nature of the focal lesions. In this study, we investigated the CK expression in both the preneoplastic lesions and extrafocal parenchyma. Sixty-seven explanted livers with cirrhosis or advanced fibrosis harboring preneoplastic focal lesions, with or without hepatitis B virus (HBV) infection, as well as 9 livers with HBV-associated fulminant hepatitis, were studied for the expression of CK7/8/14/18/19. Five livers from woodchucks infected with the woodchuck hepatitis virus (WHV) were also investigated. Glycogenotic clear hepatocytes were negative or weakly positive for CK8/18, while amphophilic hepatocytes were strongly positive for these CKs, the changes being associated with marked reduction and increase, respectively, of highly organized membranous components in their cytoplasm. This allows the distinct recognition of the clear-cell and clear-cell-dominant preneoplastic lesions in the human and woodchuck livers. In ground-glass hepatocytes expressing viral antigens, an unusual accumulation of CK8/18 was observed, but there was no evidence of preferential necrosis of ground-glass hepatocytes. Many CK7- and CK19-positive ductular (oval) cells were found in extrafocal liver tissue, but only rarely were they present within focal lesions.

Adult↗
PubMed1998

Incidence, prevalence, and clinical outcome of hepatitis GB-C virus infection in liver transplant patients.

A novel RNA virus of the Flaviviridae family has been discovered recently and designated hepatitis GB-C virus (GBV-C). Previous studies have reported that GBV-C is associated with posttransfusion hepatitis, chronic viral hepatitis, and cryptogenic hepatitis. However, the clinical significance of GBV-C infection has been questioned increasingly in patients not undergoing transplantation. To investigate whether GBV-C infection under immunosuppression affects the clinical or the histological outcome in liver transplant recipients, we determined the prevalence and incidence of GBV-C infections and the clinical and histological signs in patients after orthotopic liver transplantation (OLT). The presence of GBV-C was tested in sera from patients before and in regular intervals up to 6 years after OLT by nested reverse transcription-polymerase chain reaction using primers derived from the NS3 region. A total of 72 patients were studied. Before OLT, 8 of 72 (11.1%) patients were positive for GBV-C. After OLT, 7 of 8 (87.5%) remained positive. Of 64 patients who were negative for GBV-C before OLT, 23 became positive after OLT, resulting in a de novo rate of GBV-C infection of 35.9%. We could not detect a higher rate of histologically proven hepatitis in GBV-C-positive patients (29.1%) than in GBV-C-negative patients (14.6%, P > 0.057). Comparing GBV-C-positive with GBV-C-negative liver transplant patients, we could not find any differences in age, gender, liver function tests, number of blood transfusions, histological degree of hepatitis, or number of rejection episodes. Survival was not negatively influenced by GBV-C positivity. In conclusion, the presence of GBV-C did not influence the clinical or histological outcome in liver transplant patients.

Adult↗
PubMed1998

The efficacy of N-acetylcysteine as a hepatoprotective agent in liver transplantation.

One of the most common complications after liver transplantation is primary graft dysfunction which results from severe deterioration of the microcirculation. The data obtained from our experimental studies indicate that N-acetylcysteine (NAC) is able to reduce the severity of ischemia/reperfusion injury and improves postoperative graft function after liver transplantation in rats. The aim of this pilot study was to evaluate the efficacy of NAC as a hepatoprotective agent under clinical conditions. A group of 30 liver transplanted patients were treated with NAC, and 30 patients (control group) were treated with a 5% solution of glucose only. In the NAC group we observed a distinct reduction in ischemia/reperfusion injury and improved liver function with less elevated peak transaminases, better macrocirculation, improved liver synthesis function and a lower incidence of primary nonfunction compared with the control group. We conclude that NAC is a very promising substance for reducing graft dysfunction in clinical liver transplantation.

Acetylcysteine↗
PubMed1998

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology.

BACKGROUND/AIMS: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure. METHODS: The 5'-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12). RESULTS: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25% and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure. CONCLUSIONS: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.

Adolescent↗
PubMed1998

Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis.

Wilson's disease can result in fulminant liver failure due to hepatic copper overload. The CD95 system mediates apoptosis and has been demonstrated to be involved in liver disease. In this study CD95 mediated apoptosis was investigated in patients with fulminant hepatic failure in the course of Wilson's disease and in an in vitro model of copper treated human hepatoma cells. In patients, hepatic expression of CD95 and CD95L mRNA and apoptosis were detected. Copper overload in vitro resulted in hepatocytic apoptosis which could be reduced with a neutralizing anti-CD95L antibody. Copper treatment of hepatocytes results in activation of the CD95 system and induction of apoptosis which is operative during the course of hepatic failure in acute Wilson's disease.

Acute Disease↗
PubMed1998

Survival and recurrence after liver transplantation versus liver resection for hepatocellular carcinoma: a retrospective analysis.

OBJECTIVE: This study compares the results of liver transplantation (LTx) and liver resection (LR) for hepatocellular carcinoma (HCC) to test the widespread hypothesis that LTx is the preferable approach for small HCCs. SUMMARY BACKGROUND DATA: With respect to scarcity of donor organs and poor results, LTxs for large HCCs are obsolete. Small HCC transplantations have been reported to result in an excellent survival rate. However, the data of comparative studies are controversial. METHODS: Patients who were treated curatively by LTx (n = 50) or LR (n = 52) for HCC were included in this retrospective study. Survival and freedom from recurrence were analyzed. Patients were stratified according to prognostic factors (pT classification, tumor size, number of tumor nodules, vascular infiltration, and cirrhosis). RESULTS: Overall, after LTx and LR the 3-year survival rate and recurrence rate were not significantly different. In the Cox analysis, tumor size (p = 0.02) and vascular infiltration (p = 0.04) were independent variables after LTx, whereas after LR, none of the tested prognostic parameters was significant. With regards to recurrence, tumor size was the only independent factor, after both LTx and LR (p = 0.02, respectively). Directly comparing the two therapeutic approaches, a 3-year survival rate in pT 1/2, oligocentric (1-5 nodules), and oligocentric and small tumors proved to be superior after LTx. The recurrence rate after LTx was superior to LR in pT 1/2 and oligocentric tumors. Remarkably, for small (< or = 5 cm) tumors, LTx and LR resulted in a similar 3-year survival rate and freedom from recurrence. CONCLUSIONS: According to our analysis, the oncological advantage of LTx compared with LR is questionable. This applies especially for small tumors. Superior results of LTx in early stage HCC and particularly in oligocentric tumors may be attributed to incorrect preoperative diagnosis. Nevertheless, LTx is a reasonable treatment for patients with early stage tumors if a LR is impossible because of tumor localization or poor functional hepatic capacity.

Adult↗
PubMed1998

Hypothermia reduces neurologic deficits associated with placement of a vascular prosthesis in the abdominal aorta of rabbits.

Treatment for atherosclerotic vascular disease in human beings ranges from medical management to interventional therapy, such as angioplasty, atherectomy, and bypass grafting. Recently, bypass grafting with a vascular prosthesis has received increased attention and clinical use. In the course of studies to optimize use of a small-caliber vascular prosthesis, five of six rabbits undergoing implantation of a polytetrafluoroethylene vascular prosthesis in the infrarenal abdominal aorta developed hind limb neurologic deficits, which resulted from focal ischemic damage to the spinal cord attributable to temporary vascular occlusion of the abdominal aorta during placement of the vascular prosthesis. In subsequent studies, induction of systemic hypothermia decreased the rate of development of neurologic deficits from 83 to 9% without any apparent perioperative complications associated with decreased body temperature. We determined that mild hypothermia (rectal temperature of 32 to 35 degrees C), combined with aortic occlusion time of < 40 min, is sufficient to afford protection from ischemic injury to the spinal cord in the rabbit.

Animals↗
PubMed1998

[Effect of a shunt on subsequent liver transplantation].

Recurrent bleeding from esophageal varices may be prevented by TIPS or surgical shunts. Both treatment options bear potential risks for a consecutive liver transplantation. TIPS may lead to severe encephalopathy, hepatic functional deterioration, shunt occlusion or dislocation. Following surgical shunts, technical difficulties during transplantation and portal vene thromboses may be encountered. Patients with foreseeable indication for liver transplantation are best treated by TIPS. In Child A and stable Child B patients surgical shunts are preferable.

Esophageal and Gastric Varices↗