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Olaf Dirsch

Publications and source records attributed to Olaf Dirsch.

At least 37 records · Page 2Linked to original sources
PubMed2004

Presence of markers for liver progenitor cells in human-derived intrahepatic biliary epithelial cells.

AIMS: Rodent intrahepatic bile duct may harbor bipotential liver progenitor cells. In this study, human-derived intrahepatic biliary epithelial cells (BECs) were investigated in terms of whether they have the character of liver progenitor cells. METHODS: Ten liver tissue specimens were obtained after partial hepatectomy or liver explantation. Intrahepatic BECs were isolated by density-gradient centrifugation and immunomagnetic separation using anti-human epithelial antigen and cultured in medium containing epidermal growth factor and hepatocyte growth factor. The isolated and cultured cells were characterized by immunostaining and reverse transcription polymerase chain reaction with a variety of markers for fetal hepatocytes and liver progenitor cells. RESULTS: These cells had proliferated for up to 18 weeks in vitro. They continuously expressed epithelial markers (cytokeratin (CK) 8 and CK 18) as well as biliary markers (CK 7 and CK 19). Remarkably, some isolated and cultured cells also expressed markers for fetal hepatocytes and liver progenitor cells, including albumin, alpha-fetoprotein, alpha1-antitrypsin, c-kit and chromogranin-A. CONCLUSION: Some human-derived intrahepatic BECs coexpressed markers for liver progenitor cells. This finding further supports the hypothesis that the human biliary tree may also consist of liver progenitor cells.

Adult↗
PubMed2004

Helper-dependent adenoviral vector-mediated delivery of woodchuck-specific genes for alpha interferon (IFN-alpha) and IFN-gamma: IFN-alpha but not IFN-gamma reduces woodchuck hepatitis virus replication in chronic infection in vivo.

Alpha interferon (IFN-alpha) and IFN-gamma are able to suppress hepadnavirus replication. The intrahepatic expression of high levels of IFN may enhance the antiviral activity. We investigated the effects of woodchuck-specific IFN-alpha (wIFN-alpha) and IFN-gamma(wIFN-gamma) on woodchuck hepatitis virus (WHV) replication in vivo by helper-dependent adenoviral (HD-Ad) vector-mediated gene transfer. The expression of biologically active IFNs was demonstrated in vitro after transduction of woodchuck cells with HD-Ad vectors encoding wIFN-alpha (HD-AdwIFN-alpha) or wIFN-gamma (HD-AdwIFN-gamma). The transduction efficacy of the HD-Ad vector in woodchuck liver in vivo was tested with a vector expressing green fluorescence protein (GFP). Immunohistochemical staining of liver samples on day 5 after injection showed expression of GFP in a high percentage of liver cells surrounding the central vein. The transduction of livers of WHV carriers in vivo with HD-AdwIFN-alpha or HD-AdwIFN-gamma induced levels of biologically active IFN, which could be measured in the sera of these animals. Expression of wIFN-alpha in the liver reduced intrahepatic WHV replication and WHV DNA in sera of about 1 log step in two of two woodchucks. Transduction with HD-AdwIFN-gamma, however, reduced WHV replicative intermediates only slightly in two of three animals, which was not accompanied with significant changes in the WHV DNA in sera. We demonstrated for the first time the successful HD-Ad vector-mediated transfer of genes for IFN-alpha and IFN-gamma in vivo and timely limited reduction of WHV replication by wIFN-alpha, but not by wIFN-gamma.

Adenoviridae↗
PubMed2003

Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT.

More than 90% of gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT, and activating mutations of the KIT gene are detectable in the vast majority of these tumors. Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Here we report a patient with metastatic GIST who responded well to imatinib mesylate treatment despite the near absence of KIT expression in two different samples of his tumor. The tumor was morphologically typical for a GIST, stained positively for CD34, and harbored an in-frame deletion (WK 557-558) in KIT exon 11 that is common in GISTs. Our experience with this patient suggests that even GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy.

Adult↗
PubMed2003

The efficiency of humoral immune transfer depends on both the graft and the immunosuppressive treatment.

The present study was designed to compare the efficiency of adoptive transfer of humoral immunity after liver, kidney, and heart transplantation in relation to the number of passenger lymphocytes, and to estimate the risk of a detrimental effect and the chance of a beneficial effect. Hepatitis B virus surface-antigen-vaccinated brown Norway rats (BNs) and AxC 9935 Irish (ACI rats) served as donors, and naïve Lewis (LEW) rats as recipients. The liver grafts contained 100 times more passenger lymphocytes than heart grafts, and the kidney grafts approximately ten times more, indicated by monoclonal CD45 antibody staining. Transient anti-HBs immunity did occur after transplantation of all three organ grafts. In all rejecting groups, the serum recipient-to-donor anti-HBs titer ratio (R/D ratio) was below 0.10%, with heart recipients showing half the level (0.05%) of liver recipients (0.09%). Under immunosuppression, R/D ratio doubled in liver or kidney recipients, but remained unaffected in heart recipients. Immune transfer was most efficient in immune-suppressed liver recipients in the spontaneously tolerant strain combination as indicated by a significantly higher R/D ratio (0.32%) and a longer titer persistence (up to 9 weeks) than in all other groups. Therefore, mainly liver and kidney graft recipients carry a risk, but also a chance of benefiting from the transfer of donor-derived immunity.

Animals↗
PubMed2003

Catheter-based coronary bypass: a development update.

Catheter-based coronary bypass has evolved since its origin in 1995. We present a status update of one version of catheter-based bypass, percutaneous in situ coronary venous arterialization (PICVA), its successes and failures, and the many questions and challenges that remain. Initial clinical experience with PICVA demonstrated promising mitigation of angina in no-option patients, but was complicated by a relatively low procedural completion rate and a high incidence of MACE. A great deal was learned in these initial cases. The system of devices is currently undergoing significant modification, and further clinical study is underway.

Cardiac Catheterization↗
PubMed2003

Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits.

To overcome the problem of in-stent restenosis, the concept of local delivery of antiproliferative or immunosuppressive drugs has been introduced into interventional cardiology. Local drug delivery can be achieved by drug-eluting stents coated with polymer surfaces used for controlled drug release. However, several polymer coatings have shown an induction of inflammatory response and increased neointima formation. In the present study, the effect of a new inorganic ceramic nanoporous aluminum oxide (Al(2)O(3)) coating on neointima proliferation and its suitability as a carrier for the immunosuppressive drug tacrolimus have been investigated. 316 L stainless steel coronary stents were coated with a 500 nm thin nanoporous aluminum oxide layer. This ceramic nanolayer was used as a carrier for tacrolimus. Bare stents (n = 6), ceramic coated stents (n = 6), and ceramic coated stents loaded with 60 (n = 7) and 120 mug (n = 6) tacrolimus were implanted in the common carotid artery of New Zealand rabbits. The ceramic coating caused no significant reduction of neointimal thickness after 28 days. Loading the ceramic stents with tacrolimus led to a significant reduction of neointima thickness by 52% for 60 mug (P = 0.047) and 56% for 120 mug (P = 0.036) as compared to the bare stents. The ceramic coating alone as well as in combination with tacrolimus led to a reduced infiltration of lymphocytes and macrophages in the intima in response to stent implantation. Ceramic coating of coronary stents with a nanoporous layer of aluminum oxide in combination with tacrolimus resulted in a significant reduction in neointima formation and inflammatory response. The synergistic effects of the ceramic coating and tacrolimus suggest that this new approach may have a high potential to translate into clinical benefit.

Animals↗
PubMed2003

Assessment of normal, inflammatory, and tumor-bearing lymph nodes with contrast-enhanced interstitial magnetic resonance lymphography: preliminary results in rabbits.

PURPOSE: To assess different gadolinium (Gd)-based contrast agents for interstitial magnetic resonance (MR) lymphography in normal, inflammatory, and tumor-bearing lymph nodes in rabbits. MATERIALS AND METHODS: Three paramagnetic contrast agents were assessed: a standard extracellular 0.5 M Gd-chelate, gadoterate meglumine (Gd-DOTA), and two macromolecular agents, P792 and P760 (all Guerbet, Aulnay-sous-Bois, France). A volume of 0.5 mL of each agent were injected subcutaneously into the dorsal footpads of six rabbits (three groups, 18 rabbits). Imaging was performed prior to as well as two weeks following induction of either reactive (complete Freund adjuvant) or tumorous (VX2 tumor) lymph nodes. T1-weighted three-dimensional gradient-echo and maximum intensity projection (MIP) images were obtained up to 120 minutes as well as 24 hours after administration of the different compounds. Signal-to-noise ratios (SNRs) of enhancing lymph nodes were calculated. The different compounds were compared regarding nodal enhancement over time, depiction of regional nodes, and lymphatic vessels. Furthermore, enhancement patterns were compared between normal, inflammatory, and metastasized nodes. RESULTS: Inguinal and iliac lymph nodes and lymph vessels revealed enhancement following interstitial injection of all evaluated compounds. For all agents, inflammatory lymph nodes revealed no significantly different SNRs compared to normal nodes (P > 0.2), whereas tumorous nodes showed signal voids and significantly lower SNRs (P < 0.05). Compared to P760 and P792, depiction of tumor-bearing nodes with Gd-DOTA was less reliable. CONCLUSION: Interstitial MR lymphography with P760 and P792 allows differentiation of tumor-bearing lymph nodes from reactive inflammatory and normal nodes based on a contrast uptake pattern assessed qualitatively as well as quantitatively.

Animals↗
PubMed2003

Amyloid of heart and lungs in a patient with low output syndrome after coronary artery bypass grafting.

A 70-year-old patient with two-vessel disease and moderately reduced left ventricular function after a recent myocardial infarction was admitted for a routine coronary artery bypass grafting (CABG) procedure. During anesthetic induction, he became unstable and cardiopulmonary bypass had to be instituted urgently. Despite good bypass flows, the patient died in myocardial failure shortly after surgery. At autopsy, besides severe atherosclerotic coronary artery disease, cardiac and pulmonary amyloidosis were found.

Aged↗
PubMed2003

Papillomatosis confined to the distal biliary tract--a rare cause of obstructive jaundice: report of a case.

Based on the findings of a patient with recurrent obstructive jaundice due to papillomatosis of the distal bile duct, we herein describe the diagnostic difficulties and therapeutic options in this very rare disease. Endoscopic retrograde cholangiopancreatography and, in particular, cholangioscopy are the imaging procedures of choice if biliary papillomatosis is suspected. Due to the tendency of such patients to demonstrate malignant transformation and develop biliary cirrhosis with septic complications, an early and radical surgical resection is recommended in rare cases of localized papillomatosis. This approach may offer the only chance of a cure although the potential risk of multifocal recurrence cannot be ruled out. When considering a radical resection, intraoperative cholangioscopy is strongly recommended to confirm any localized papillomatosis and rule out any diffuse papillomatosis of the entire biliary tract.

Adenoma↗
PubMed2003

Efficacy of combined lamivudine and adefovir dipivoxil treatment for severe HBV graft reinfection after living donor liver transplantation.

Resistance to lamivudine and hyperimmune globulin (HBIG) may cause severe graft reinfection with progression to fulminant hepatic failure in liver transplant recipients. In this report, we describe the clinical course of a patient with perinatally acquired chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma who developed severe fibrosing cholestatic hepatitis after living donor liver transplantation because of the emergence of lamivudine and HBIG-resistant chronic hepatitis B. Immunohistochemistry demonstrated that more than 30% of hepatocytes stained positively for hepatitis B core antigen. Hepatitis B virus sequence analysis revealed several mutations in the polymerase gene (L528M, M552I, M552V) as well as in the surface gene region encoding the immunogenic major hydrophilic loop of the small surface protein (G130N, M133T, D144G). The amino acid exchange at codon 144 has already been described to escape neutralization by HBIG. Combined treatment with lamivudine and adefovir dipivoxil (ADV) was associated with a dramatic biochemical, virological and clinical response with resolution of jaundice, ascites, peripheral edema and pleural effusions. Serum bilirubin normalized, HBV DNA levels significantly decreased and liver biopsy was remarkable for the absence of viral protein. These results indicate that ADV may provide a sustained rescue treatment for aggressive courses of HBV graft reinfection in liver transplant recipients.

Adenine↗
PubMed2002

A new model of hepatitis B virus reinfection: liver transplantation in the woodchuck1.

BACKGROUND: Reinfection of liver grafts with hepatitis B virus (HBV) is a pertinent problem in clinical liver transplantation, requiring the development of new treatment strategies. However, no animal model is currently available to study the course and mechanism of hepatitis B reinfection. This was the reason to establish the technique of liver transplantation in the woodchuck, which is a widely used animal model for HBV infection. MATERIAL AND METHODS: For the reinfection study, woodchuck hepatitis virus (WHV)-negative animals were selected as donors, whereas chronic carriers served as recipients (n=3). Immunosuppression consisted of cyclosporine in a daily dose of 5 mg/kg. Blood and liver samples were obtained before and 8 hr, 3 weeks, and 10 weeks after transplantation. Virological markers included serological testing for WHV DNA, WHV surface antigen (WHsAg), core antigen (WHcAg), and their antibodies (anti-WHs and anti-WHc). WHV DNA replication intermediates and viral RNA were detected by Southern blot hybridization and Northern blot, respectively. Viral proteins in the liver were visualized by immunohistochemistry for WHsAg and WHcAg. RESULTS: Early after transplantation membranous but no intracytoplasmic staining for WHsAg was detected in the liver graft, which was negative for WHcAg as well as WHV-DNA and RNA. Nearly all hepatocytes in the liver grafts of animals killed at 3 weeks and 10 weeks posttransplant showed strong membranous (WHsAg) and intracytoplasmic (WHsAg and WHcAg) staining, which was higher in frequency and intensity than in carriers before transplantation. The apparently reduced level of WHV replication intermediates and viral RNA in the reinfected liver grafts compared with the carrier animals was caused by the severe morphological changes leading to a replacement of hepatocytes by extended portal infiltrates. CONCLUSION: The woodchuck proved to be a suitable model to study WHV reinfection after liver transplantation, because the operative procedure was well tolerated. The first sign of viral presence in the graft was WHsAg detected exclusively in the sinusoids. Reinfection was proven by heavy intracytoplasmic staining for WHsAg and WHcAg in the majority of hepatocytes and detection of viral DNA and RNA in the graft.

Animals↗
PubMed2002

Extraction of large intracoronary thrombus in acute myocardial infarction by percutaneous Fogarty maneuver: intentional abuse of a novel interventional device.

Intracoronary thrombus in the infarct-related artery remains a challenge for interventional catheter-based techniques in acute myocardial infarction and may result in severe complications due to distal embolization. We describe a patient with acute myocardial infarction in whom a large intracoronary thrombus of the left anterior descending coronary artery was successfully removed by percutaneous Fogarty maneuver using an expanded filter protection device.

Adult↗
PubMed2002

Modified sleeve anastomosis for reconstruction of the hepatic artery in rat liver transplantation.

End-to-end sleeve anastomosis between a donor common hepatic artery and a recipient proper hepatic artery was proven to be the most physiological and simple method for hepatic rearterialization in rat liver transplantation. Current technical variants of the sleeve technique, however, are hampered by the high rate of bleeding from the anastomotic site. This report deals with a technical modification which inhibits postoperative bleeding efficiently. The procedure consisted of a guiding suture, as previously described in other technical variants, and a modified fixing suture. Instead of using a single stitch to fix the feeding vessel with the receiving vessel, a running suture between the edge of the donor common hepatic artery and the adventitia of the recipient proper hepatic artery was performed to avoid a possible backflow. The patency rate of 91% was as high as reported by others using a sleeve technique, which was also reflected in the histomorphological picture, being indistinguishable from normal liver histology. This technical modification simplified the procedure of reconstructing the hepatic artery and could contribute to a wider use of the arterialized liver transplantation model in rats.

Anastomosis, Surgical↗
PubMed2002

Improved renal transplantation in the rat with a nonsplinted ureteroureterostomy.

Orthotopic renal transplantation in the rat is a widely used model in immunology and transplantation-related research. Although numerous modifications of the surgical technique of ureteric reconstruction were evaluated, ureter complications following this reconstruction still occurred frequently. Instead of dividing the ureter in the middle between kidney and bladder (method 1), the anastomosis was performed close to the renal pelvis after cutting the ureter obliquely (method 2), which enlarged the diameter of the ureteral anastomosis 2-fold. The incidence of stenosis of ureteric anastomosis was 12.5% (3/24) using method 1, whereas this complication was avoided completely (0/45) using method 2. Furthermore, the risk of injury to the ureter was reduced, as isolation of the ureter was limited. These modifications improved the last delicate step in the procedure of rat kidney transplantation.

Anastomosis, Surgical↗
PubMed2002

Stent coating: a new approach in interventional cardiology.

BACKGROUND: Since its introduction in clinical cardiology, several studies have shown the superiority of coronary stent implantation as compared to conventional angioplasty. However, restenosis still remains a major drawback of this new technique. Basic research in animal models could identify stent-related factors like stent-material and stent-design as major determinants of intima proliferation. Since materials with good biocompatibility often have unsuitable mechanical properties and vice versa, the concept of stent coating has been developed to allow the combination of favorable characteristics from different materials. PASSIVE COATING: In general, passive coatings, which only serve as a barrier between the stainless steel and the tissue, and active coatings, which directly interfere with the process of intima proliferation have been identified. Currently there are several passive coatings commercially available with good results in animal models and preliminary reports from clinical studies. ACTIVE COATING: As any surface induces some kind of tissue reaction promoting restenosis, an active stent coating with antiproliferative drugs has been proposed. However, while animal studies revealed convincing results, preliminary clinical studies not only showed active stent coating effective in preventing restenosis, but also demonstrated the potential risks of this new approach. Although this technique may harbor some specific risks, with the introduction of stent coating a new chapter of interventional cardiology has been flipped open.

Angioplasty, Balloon, Coronary↗
PubMed2002

Adoptive transfer of HBV immunity by kidney transplantation and the effect of postoperative vaccination.

Transfer of hepatitis B immunity occurs upon the transfer of immunologically active cells from the donor to the recipient by means of an organ graft. This has been repeatedly demonstrated for bone marrow and liver transplantations. Evidence is now presented for the transfer of anti-hepatitis B surface antibodies (anti-HBs) after kidney transplantation in rats. Kidney donors from one syngeneic and two allogeneic rat strains were immunized twice with 4 microg of recombinant hepatitis B vaccine. In week 6 after the first vaccination, kidney grafts were transplanted into Lewis (LEW) rats. Half of the recipients underwent daily immunosuppressive treatment with cyclosporin A (CsA). All recipients were vaccinated either after 10 weeks or 1 week postoperatively. Anti-HBs titer was measured weekly. Effective anti-HBs titers (10-227 mIU/ml, lasting for 1-7 weeks) were detected in 86% (25/29) of recipient rats, whose corresponding donors all had a titer above 15,000 mIU/ml. Immunosuppression enhanced the donor-derived immunity in terms of recipient-to-donor titer ratio, maximal titer and titer persistence.

Adoptive Transfer↗
PubMed2002

Repeated detection of gas in the portal vein after liver transplantation: A sign of EBV-associated post-transplant lymphoproliferation?

A 1-yr-old child presented with intractable right sided pleural effusion and progressive clinical deterioration 3 weeks after liver transplantation for Alagille Syndrome. He had been treated successfully for severe acute rejection before. Ultrasound and Doppler mode studies repeatedly demonstrated air in the portal vein. Intra-abdominal and intra-thoracic lymphoproliferation was detected, and EBV virus load and serology were suggestive of primary EBV infection. Liver biopsy revealed blast-like infiltrates of B-cells, considered diagnostic for post-transplant lymphoproliferative disease. The disease resolved upon reduction of immunosuppression. We suggest that the detection of portal vein gas in pediatric liver transplant recipients beyond the early post-operative period may be a sign of intra-abdominal post-transplant lymphoproliferative disease.

Alagille Syndrome↗