8 results on '"McNally, Richard J.Q."'
Search Results
2. PBC triggers in water reservoirs, coal mining areas and waste disposal sites: From Newcastle to New York.
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McNally, Richard J.Q., Smyk, Daniel, Mytilinaiou, Maria G., Rigopoulou, Eirini I., and Bogdanos, Dimitrios P.
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CIRRHOSIS of the liver , *RESERVOIRS , *COAL mining , *WASTE disposal sites , *IMMUNOLOGICAL tolerance , *AUTOIMMUNITY , *BILE duct diseases , *CHOLESTASIS , *MIMICRY (Chemistry) - Abstract
Various environmental factors have been proposed as triggers of primary biliary cirrhosis (PBC), a progressive autoimmune cholestatic liver disease which is characterised by the destruction of the small intrahepatic bile ducts. Support for their pathogenic role in PBC is provided by epidemiological studies reporting familial clustering and clusters of the disease within a given geographical area. The seminal study by Triger reporting that the great majority of PBC cases in the English city of Sheffield drank water from a specific water reservoir, has been followed by studies reporting disease 'hot spots' within a restricted geographic region of the former coal mining area of Newcastle. The New York study reporting an increased risk and significant clustering of PBC cases near toxic federal waste disposal sites has added strength to the notion that environmental factors, possibly in the form of infectious agents or toxic/chemical environmental factors in areas of contaminated land, water or polluted air may play a key role in the development of the disease. This review discusses the findings of reports investigating environmental factors which may contribute to the cause of primary biliary cirrhosis. [ABSTRACT FROM AUTHOR]
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- 2010
3. Infectious agents and xenobiotics in the etiology of primary biliary cirrhosis.
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McNally, Richard J.Q., Selmi, Carlo, De Santis, Maria, Cavaciocchi, Francesca, and Gershwin, M. Eric
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CIRRHOSIS of the liver , *ETIOLOGY of diseases , *XENOBIOTICS , *RESTRICTED environmental stimulation , *MITOCHONDRIAL DNA , *SEROLOGY , *AUTOANTIBODIES - Abstract
Primary biliary cirrhosis (PBC)is a chronic autoimmune cholestatic liver disease that manifests a latitudinal gradient in prevalence and incidence. The mechanisms leading to the initiation and perpetuation of PBC remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. PBC is also characterized by a high concordance rate in monozygotic twins and is considered a model autoimmune disease because of several features common to other conditions and the relatively homogeneous serological and biochemical features. From a diagnostic standpoint, PBC is characterized by the highest specificity of serum autoantibodies directed at mitochondrial proteins. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics that will be critically discussed in the present review article. [ABSTRACT FROM AUTHOR]
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- 2010
4. The role of E. coli infection in the pathogenesis of primary biliary cirrhosis.
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McNally, Richard J.Q., Bogdanos, Dimitrios P., Baum, Harold, Vergani, Diego, and Burroughs, Andrew K.
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ESCHERICHIA coli diseases , *CIRRHOSIS of the liver , *EPIDEMIOLOGY , *URINARY tract infections , *IMMUNE response , *IMMUNOLOGICAL tolerance , *CHOLESTASIS , *AUTOIMMUNITY - Abstract
Among various infectious agents possibly involved in the pathogenesis of primary biliary cirrhosis (PBC), Escherichia Coli (E. coli) has received special attention because of epidemiological and experimental evidence linking this bacterium with the disease's development. This review discusses early and more recent epidemiological studies associating recurrent urinary tract infections with E. coli and the development of PBC. We also critically review data provided over the years demonstrating disease-specific humoral and cellular immune responses against E. coli antigens in patients with PBC. Finally, we assess the relevance of experimental findings reporting cross-reactive immunity between mimicking sequences of E. coli and the major PBC mitochondrial antigens in the pathogenesis of the PBC. We also address the extent to which molecular mimicry and immunological cross-reactivity can be considered as a critical pathogenic process linking infection with self destruction. [ABSTRACT FROM AUTHOR]
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- 2010
5. Primary biliary cirrhosis: Environmental risk factors.
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McNally, Richard J.Q., Dronamraju, Deepti, Odin, Joseph, and Bach, Nancy
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CIRRHOSIS of the liver , *AUTOIMMUNE diseases , *ETIOLOGY of diseases , *CHOLESTASIS , *CAUCASIAN race , *XENOBIOTICS , *EPIDEMIOLOGY - Abstract
Primary biliary cirrhosis (PBC) is an autoimmune disease of unclear etiology. It is a chronic, progressive condition that causes intrahepatic ductal destruction ultimately leading to symptoms of cholestasis, cirrhosis and liver failure. The disease predominantly affects middle aged Caucasian women. It has a predilection to certain regions and is found in higher incidences in North America and Northern Europe. It also has a genetic predisposition with a concordance rate of 60% among monozygotic twins. Combinations of genetic and environmental factors are proposed in the pathogenesis of this disease with a compelling body of evidence that suggests a role for both these factors. This review will elucidate data on the proposed environmental agents involved the disease's pathogenesis including xenobiotic and microbial exposure and present some of the supporting epidemiologic data. [ABSTRACT FROM AUTHOR]
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- 2010
6. Infectious agents in the pathogenesis of primary biliary cirrhosis.
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McNally, Richard J.Q., Ortega-Hernandez, Oscar-Danilo, Levin, Nancy-Agmon, Altman, Arie, and Shoenfeld, Yehuda
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CIRRHOSIS of the liver , *PYRUVATES , *MOLECULAR mimicry , *IMMUNOLOGICAL tolerance -- Molecular aspects , *EPIDEMIOLOGY , *AMINO acid sequence , *AUTOIMMUNITY - Abstract
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease which is characterized by the breakdown of self-tolerance to the highly conserved pyruvate dehydrogenase complex, specially the pyruvate dehydrogenase E2 complex (PDC-E2). The breakdown of the tolerance to such antigens leads to an autoimmune process characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Epidemiological studies have suggested that infections agents can trigger or even exacerbate the disease. Among other gram negative bacteria, Escherichia Coli, and Nosphingobium aromaticivorans are the most associated agents reported hitherto. Epidemiological and molecular evidence points towards molecular mimicry between some components of these microorganisms and specific amino-acid sequences that are present in proteins on normal cells of the biliary tract. In this review, we revisit all reports suggesting that infectious agents might be associated with the autoimmune pathogenesis of PBC. We also retrieve the immune molecular mimicry mechanisms that are likely involved with the autoimmune process in PBC. [ABSTRACT FROM AUTHOR]
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- 2010
7. Infection as a risk factor in the pathogenesis of primary biliary cirrhosis: Pros and cons.
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McNally, Richard J.Q., Kumagi, Teru, Abe, Masanori, Ikeda, Yoshiou, and Hiasa, Yoichi
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CIRRHOSIS of the liver , *DISEASE risk factors , *CASE-control method , *ETIOLOGY of diseases , *GENETICS of disease susceptibility , *XENOBIOTICS , *IMMUNOLOGICAL tolerance - Abstract
Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology, characterized by injury of the intrahepatic bile ducts that may eventually lead to cirrhosis and liver failure. Evidence suggests cardinal roles for both environmental factors and genetic susceptibility. Nevertheless, the absolute etiology of PBC is unclear, despite recent well-designed case-control studies that reported environmental risk factors, including infectious agents, for PBC. Of the reported infectious agents, some of them are not reproducible and remain controversial. However, infection is no doubt one of the major risks among the environmental factors. This is supported by the fact that infectious agents in autoimmune diseases express antigens resulting in molecular mimicry and xenobiotics that play a role in breaking tolerance. Taken together, recent findings from genome wide assays as well as novel animal models may enable us to better understand the mechanism of pathogenesis responsible for this disease. [ABSTRACT FROM AUTHOR]
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- 2010
8. Environmental agents involved in the cause of primary biliary cirrhosis.
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McNally, Richard J.Q. and Kouroumalis, Elias
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CIRRHOSIS of the liver , *ETIOLOGY of diseases , *AUTOIMMUNE diseases , *SEROLOGY , *XENOBIOTICS , *EPIDEMIOLOGY - Abstract
Primary biliary cirrhosis (PBC) is an immune mediated chronic cholestatic liver disease with a slowly progressive course It is a universal disease with a reported latitudinal gradient in prevalence and incidence. The aetiology of primary biliary cirrhosis is still unknown. It is characterized by a 60% concordance in monozygotic twins and is considered an autoimmune disease because of several features common to other autoimmune conditions and the relatively homogeneous serological and biochemical features. However geoepidemiological and clinical studies strongly imply that environmental factors also play an important role. It is accepted that the disease is clearly the result of a combination of genetic and environmental factors. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics. This review will attempt to place such factors in perspective. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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