Search results for " Pathogenesis"
showing 10 items of 71 documents
Desmin‐related Myopathies
2006
Outstanding progress in elucidating the pathology of muscular disorders at light and electron microscopic levels has allowed the identification of proteins involved in pathological alterations. This, in turn, has led to discoveries of multiple genes and mutations associated with previously poorly understood conditions. An unexpected result is that phenotypically similar and pathogenetically related neuromuscular disorders are associated with mutations in one or the other of several interacting proteins. Keywords: desmin-related myopathy; distal myopathy; cardiomyopathy; desmin and alpha-B crystallin gene mutations; functional analysis; molecular pathogenesis; genotype–phenotype correlations
Multiple infection dynamics has pronounced effects on the fitness of RNA viruses
2001
Several factors play a role during the replication and transmission of RNA viruses. First, as a consequence of their enormous mutation rate, complex mixtures of genomes are generated immediately after infection of a new host. Secondly, differences in growth and competition rates drive the selection of certain genetic variants within an infected host. Thirdly, but not less important, a random sampling occurs at the moment of viral infectious passage from an infected to a healthy host. In addition, the availability of hosts also influences the fate of a given viral genotype. When new hosts are scarce, different viral genotypes might infect the same host, adding an extra complexity to the comp…
Cytomegalovirus inhibits the engraftment of donor bone marrow cells by downregulation of hemopoietin gene expression in recipient stroma
1998
ABSTRACT Cytomegalovirus (CMV) disease after bone marrow (BM) transplantation is often associated with BM graft failure. There are two possible reasons for such a correlation. First, a poor hematopoietic reconstitution of unrelated etiology could promote the progression of CMV infection by the lack of immune control. Alternatively, CMV infection could interfere with the engraftment of donor BM cells in recipient BM stroma. Evidence for a causative role of CMV in BM aplasia came from studies in long-term BM cultures and from the murine in vivo model of CMV-induced aplastic anemia. A deficiency in the expression of essential stromal hemopoietins, such as stem cell factor (SCF), has indicated …
Hepatozelluläres Karzinom - molekulare Grundlagen und Zielmoleküle für die Therapie
2012
Das hepatozellulare Karzinom zahlt zu den haufigsten Krebserkrankungen weltweit mit einer steigenden Inzidenz in westlichen Landern. Leberzellkarzinome zeichnen sich durch eine molekulare Vielfalt und ein schlechtes Therapieansprechen aus. Trotz groser Fortschritte in der Diagnostik und Behandlung des Leberzellkarzinoms in den letzten Jahren bleiben die Details der biochemischen Mechanismen weitestgehend unverstanden. Hierdurch wird die Entwicklung neuer Therapiestrategien erheblich erschwert. Die rasante Entwicklung von neuen Verfahren zur Analyse molekularer Mechanismen der Krebsentstehung auf verschiedenen molekularen Ebenen hat wesentlich zum Verstandnis der Hepatokarzinogenese beigetra…
Hepatitis viruses: live and let die.
2007
Viral hepatitis is a diffuse inflammatory reaction of the liver caused by hepatotropic viruses. Among the hepatitis viruses, only hepatitis B virus and hepatitis C virus are able to persist in the host and cause chronic hepatitis. In the course of persistent infection, inflammation forms the pathogenetic basis of chronic hepatitis that can lead to nodular fibrosis, which can progress to cirrhosis and, eventually, hepatocellular carcinoma (HCC). Of the different antiviral defense systems employed by the host, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Pathomorphologic studies have shown acidophilic bodies and hepatocyte dropout…
Vibrio vulnificus biotype 2 serovar E gne but not galE is essential for lipopolysaccharide biosynthesis and virulence
2008
ABSTRACT This work aimed to establish the role of gne (encoding UDP-GalNAc 4-epimerase activity) and galE (encoding UDP-Gal-4-epimerase activity) in the biosynthesis of surface polysaccharides, as well as in the virulence for eels and humans of the zoonotic serovar of Vibrio vulnificus biotype 2, serovar E. DNA sequence data revealed that gne and galE are quite homologous within this species (≥90% homology). Mutation in gne of strain CECT4999 increased the surface hydrophobicity, produced deep alterations in the outer membrane architecture, and resulted in noticeable increases in the sensitivity to microcidal peptides (MP), to eel and human sera, and to phagocytosis/opsonophagocytosis. Furt…
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
2015
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Severe reduction of blood lysosomal acid lipase activity in cryptogenic cirrhosis: A nationwide multicentre cohort study
2017
Background and aims Blood lysosomal acid lipase (LAL) is reduced in non-alcoholic steatohepatitis, which is the major cause of cryptogenic cirrhosis (CC); few data on LAL activity in CC do exist. We investigated LAL activity in a cohort of patients with liver cirrhosis. Methods This is a multicentre cohort study including 274 patients with liver cirrhosis of different aetiology from 19 centres of Internal Medicine, Gastroenterology and Hepatology distributed throughout Italy. Blood LAL activity (nmol/spot/h) was measured with dried blood spot extracts using Lalistat 2. Results Overall, 133 patients had CC, and 141 patients had cirrhosis by other causes (61 viral, 53 alcoholic, 20 alcoholic …
Phytopathogenic Bacteria Associated with Bacterioses of Common Oak (Quercus robur L.) in Ukraine
2022
Studying the biological characteristics of the causative agents of bacteriosis of the common oak (Quercus robur L.) (to highlight the links between the key factors of pathogenesis and bacterial groups) is a new and relevant area of research. This work aims to identify the species composition of phytopathogenic bacteria associated with common oak bacteriosis and to study the morphological, cultural, and biochemical properties of pathogens. To establish the general phytosanitary state of the surveyed stands, classical forest inventory and phytopathological (visual on based on typical symptoms of the disease and macroscopic) methods were used. The properties of isolated bacteria were studied u…
Control of cytomegalovirus in bone marrow transplantation chimeras lacking the prevailing antigen-presenting molecule in recipient tissues rests prim…
1998
ABSTRACT Cytomegalovirus (CMV) infection during the transient immunodeficiency after bone marrow transplantation (BMT) develops into disease unless antiviral CD8 T cells are restored in due course. Histoincompatibility between donor and recipient is associated with increased risk. Complications may include a rejection response against the foreign major histocompatibility complex (MHC) antigens and a lack of antiviral control resulting from a misfit between donor-derived T cells and the antigenic viral peptides presented in recipient tissues. Here we have established a murine model of CMV disease after experimental BMT performed across a single MHC class I disparity. Specifically, BALB/c bon…