Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge.
View Article and Find Full Text PDFBackground: Ischemia/reperfusion injury after liver transplantation (LT) may be associated with primary graft dysfunction (PDF) or non-function. Prostaglandins were demonstrated to be beneficial in reducing ischemic injury by improving microcirculation and protecting endothelial cells. The aim of this study was to analyze the effect of the continuously administered prostaglandin I(2) analog iloprost on allograft function after LT.
View Article and Find Full Text PDFBackground: There are only a few reports about combined heart-liver transplantations. The surgical techniques differ widely, ranging from sequential implantation of the organs to simultaneous transplantations. We report our experience with simultaneous, combined heart-liver transplantations without using a veno-venous bypass demonstrating that this is a feasible surgical technique.
View Article and Find Full Text PDFAlphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (NRAMP) as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells.
View Article and Find Full Text PDFCYP2D6 is part of the cytochrome P450 system, which catalyzes biotransformation of endogenous substrates and xenobiotics. Approximately 10% of the Caucasian population has two null alleles, resulting in a poor metabolizer (PM) status. Mostly, allele four (CYP2D6*4) is responsible for the PM status, which is suspected to be associated with an accelerated fibrosis progression (FP).
View Article and Find Full Text PDFBackground: Incisional hernias are a frequent problem after liver transplantation. Mesh repair techniques including laparoscopic repair have been employed in order to address this problem. We have introduced intraperitoneal onlay mesh repair (IPOM) in 2008 because of advantages that had been reported in the literature.
View Article and Find Full Text PDFAim: To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs).
Methods: A total of 333 participants were randomized 1:1 to undergo TPMT genotyping prior to azathioprine or to commence treatment without genotyping.
Results: There was no difference in the primary outcome of stopping azathioprine due to an adverse reaction (ADR, p = 0.
The aim of this analysis was to provide an update on the current trend in living donor liver transplantation (LDLT) for adult recipients in the model of end stage liver disease (MELD) era in Germany and to encourage a wider implementation of LDLT. We descriptively analysed the data of LDLTs in Germany from 15 December 2006 to 31 December 2009 using a multi-center retrospective analysis via a questionnaire and data provided by Eurotransplant. Ten German centers performed LDLTs in adults.
View Article and Find Full Text PDFPurpose: Prognosis after resection of liver metastases of colorectal cancer is influenced by a variety of clinical factors. For more than 20 years, efforts have been made to restructure and simplify prognostic parameters into clinical scores. We evaluated the influence of various clinical and pathological factors on survival and recurrence and developed a simple model for risk stratification.
View Article and Find Full Text PDFBackground: The long-term prognosis of arteriovenous (AV) polytetrafluoroethylene (PTFE) hemodialysis grafts is dissatisfying. Responsible for the poor outcome is a stenosis of the venous anastomosis. This originates from both pseudointimal (PI) and neointimal hyperplasia (IH) development.
View Article and Find Full Text PDFHighly pathogenic H5N1 influenza infections are associated with enhanced inflammatory and cytokine responses, severe lung damage, and an overall dysregulation of innate immunity. C3, a member of the complement system of serum proteins, is a major component of the innate immune and inflammatory responses. However, the role of this protein in the pathogenesis of H5N1 infection is unknown.
View Article and Find Full Text PDFIntroduction: Drug-induced tubulointerstitial nephritis and acute tubular necrosis are common, and are often caused by drugs especially antibiotics or non-steroidal anti-inflammatory drugs. Drug-induced liver dysfunction and renal failure after subcutaneous injection of phosphatidylcholine was not reported so far. 3-sn-Phosphatidylcholine has been described as a cell lysis reaction-inducing drug.
View Article and Find Full Text PDFBackground: This study is a clinical characterization of keloid scars in an African population comprising three rural tribes with familial keloids. Site distribution, morphologic features, and other characteristics of the scars were studied to assess whether each tribe had a specific scar phenotype.
Methods: Keloid scar clinics were set up at Soba Hospital in Khartoum, Sudan, for patient recruitment and management.
Metacognitive training (MCT) for patients with schizophrenia is a novel psychological group treatment targeting cognitive biases putatively involved in the pathogenesis of schizophrenia (e.g. jumping to conclusions, overconfidence in errors).
View Article and Find Full Text PDFChikungunya virus (CHIKV), an emerging mosquito-borne Alphavirus, causes debilitating rheumatic disease in humans that can last for weeks to months. Starting in 2004, a CHIKV outbreak in the Indian Ocean region affected millions of people, and infected travelers introduced CHIKV to new regions. The pathogenesis of CHIKV is poorly understood, and no approved vaccines or specific therapies exist.
View Article and Find Full Text PDFThe viral determinants of alphavirus-induced rheumatic disease have not been elucidated. We identified an RRV strain (DC5692) which, in contrast to the T48 strain, does not induce musculoskeletal inflammation in a mouse model of RRV disease. Substitution of the RRV T48 strain nonstructural protein 1 (nsP1) coding sequence with that from strain DC5692 generated a virus that was attenuated in vivo despite similar viral loads in tissues.
View Article and Find Full Text PDFNewly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages.
View Article and Find Full Text PDFStudies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross.
View Article and Find Full Text PDFBackground: Gastric cancer is one of the most frequent malignancies worldwide. More than 50% of all patients present with advanced stage of disease, with long-time survival of less than 5%. In selected subgroups, palliative gastric resection seems to be beneficial for survival and improved quality of the remaining life time, but is still controversially discussed.
View Article and Find Full Text PDFReplacing an infected prosthesis with a bioimplant provides a hopeful alternative in septic vascular surgery. The objective of this study was to determine the effect of fibroblast endothelial growth factors (FGF) and vascular endothelial growth factors (VEGF) coating on a decellularized vascular graft in a rat model and the possible impact on recellularization processes. Rat aortas were decellularized, crosslinked with genipin, and coated with poly-(D, L) lactide containing either FGF or VEGF.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
June 2010
We present numerical simulations as well as experimental results concerning transitions between Taylor vortices and spiral vortices in the Taylor-Couette system with rigid, nonrotating lids at the cylinder ends. These transitions are performed by wavy structures appearing via a secondary bifurcation out of Taylor vortices and spirals, respectively. In the presence of these axial end walls, pure spiral solutions do not occur as for axially periodic boundary conditions but are substituted by primary bifurcating, stable wavy spiral structures.
View Article and Find Full Text PDFHepatocellular carcinoma and cholangiocarcinoma are relatively rare tumors of the gastrointestinal tract in western Europe but their incidence has been increased in recent years. Newly diagnosed intrahepatic lesions or intrahepatic cholestasis require extensive laboratory tests and imaging studies in order to confirm the diagnosis of hepatocellular carcinoma, intrahepatic or extrahepatic cholangiocarcinoma. The treatment options range from liver resection or liver transplantation to conservative measures (in cases of non-resectable lesions).
View Article and Find Full Text PDFPrevious studies with Venezuelan equine encephalitis virus and Sindbis virus (SINV) indicate that alphaviruses are capable of suppressing the cellular response to type I and type II interferons (IFNs) by disrupting Jak/STAT signaling; however, the relevance of this signaling inhibition toward pathogenesis has not been investigated. The relative abilities of neurovirulent and nonneurovirulent SINV strains to downregulate Jak/STAT signaling were compared to determine whether the ability to inhibit IFN signaling correlates with virulence potential. The adult mouse neurovirulent strain AR86 was found to rapidly and robustly inhibit tyrosine phosphorylation of STAT1 and STAT2 in response to IFN-γ and/or IFN-β.
View Article and Find Full Text PDFBackground: Extrahepatic portal vein thrombosis, not associated with cirrhosis or tumours, is the second most frequent cause of portal hypertension worldwide. Especially in children, anatomic mesenterico-portal interposition (REX-shunt) has become an established treatment. The changes in hepatic microcirculation after reperfusion of the shunt have not been investigated so far.
View Article and Find Full Text PDF