1,510 research outputs found
Primary biliary cirrhosis
No full textPrimary biliary cirrhosis is a chronic liver disease characterised by intrahepatic bile-duct destruction, cholestasis, and, in some cases, cirrhosis. Evidence supporting the autoimmune nature of this disorder includes the appearance of highly specific antimitochondrial antibodies (AMAs) and autoreactive T cells. Concordance rates in monozygotic twins, familial prevalence, and genetic associations underscore the importance of genetic factors, whereas findings of epidemiological studies and murine models suggest a possible role for exogenous chemicals and infectious agents through molecular mimicry. The incidence of primary biliary cirrhosis has increased over recent decades, possibly attributable to augmented testing of liver biochemistry rather than a rise in disease incidence. AMAs remain the hallmark of diagnosis in most cases and allow detection of asymptomatic patients. Symptomatic individuals usually present with either pruritus or fatigue and, more rarely, with either jaundice or complications of cirrhosis. The prognosis of primary biliary cirrhosis has improved because of early diagnosis and use of ursodeoxycholic acid, the only established medical treatment for this disorder. Although not a cure, treatment can slow disease progression and delay the need for liver transplantation. However, some patients do not respond adequately to ursodeoxycholic acid and might need alternative therapeutic approaches
Fleming, R.L. Sr., Fleming, R.L., Jr. & Bangdel, L.S. — Birds of Nepal, with reference to Kashmir and Sikkim. Katmandu, Nepal, chez le senior author (Box 229), 1976
No full textBourlière François. Fleming, R.L. Sr., Fleming, R.L., Jr. & Bangdel, L.S. — Birds of Nepal, with reference to Kashmir and Sikkim. Katmandu, Nepal, chez le senior author (Box 229), 1976. In: La Terre et La Vie, Revue d'Histoire naturelle, tome 31, n°2, 1977. p. 348
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Immune sera recognize on erythrocytes a Plasmodium falciparum antigen composed of repeated amino acid sequences
No full textAbstract not availableRoss L. Coppel, Alan F. Cowman, Robin F. Anders, Albert E. Bianco, Robert B. Saint, Klaus R. Lingelbach, David J. Kemp & Graham V. Brow
Epidemiology and pathogenesis of primary biliary cirrhosis
No full textPrimary biliary cirrhosis is an autoimmune disease of unknown etiology leading to progressive destruction of small intrahepatic bile ducts and eventually to liver cirrhosis and failure. It is characterized by female predominance (with most cases observed between the ages of 40 and 60) and serum autoantibodies to mitochondrial antigens as highly specific hallmarks. Epidemiologic data indicate a variable incidence and prevalence of the disease. A number of genetic factors have been indicated as playing a role in determining disease susceptibility or progression, although no definitive conclusion has been reached so far. However, as suggested by some epidemiologic observations, a number of environmental factors, including molecular mimicry by either microorganisms or xenobiotics, have also been proposed. A hypothesis gaining support is that environmental factors may trigger disease in genetically predisposed individuals. In this review, the available data regarding the epidemiology and pathogenesis of primary biliary cirrhosis will be described and discussed
Lack of immunological or molecular evidence for a role of mouse mammary tumor retrovirus in primary biliary cirrhosis
No full textBackground & Aims: Recent observations, including a pilot clinical trial, have suggested that a human mouse mammary tumor virus (MMTV) causes primary biliary cirrhosis (PBC). We attempted to confirm such data. Methods: We obtained sera from 101 patients (53 with PBC and 48 controls), fixed liver sections from 10 patients (8 PBC and 2 controls), fresh liver specimens (6 PBC and 6 controls), and fresh peripheral blood lymphocytes (PBLs) (10 PBC and 10 controls). We studied sera for reactivities against 3 different strains of MMTV virions, MMTV(C3H), MMTV(FM), and MMTV(LA), including goat polyclonal antibodies against MMTV virions, gp52, and p27 as positive controls. We stained liver specimens using polyclonal antibodies against MMTV and gp52 and further examined tissue samples and PBLs for specific MMTV genome sequences. Results: By Western blot analysis, no detectable reactivity in any of the PBC sera against any of the 3 MMTV strains or MMTV gp52 or p27 was observed. However, viral proteins were recognized by our control positive polyclonal antibodies. We note that 13%-60% of PBC sera presented low reactivity against 2 proteins of approximately 57 and 74 kilodaltons. Such reactivity is related to the trace amounts of mitochondrial antigens in the virus preparations derived from murine mammary tumor tissue. No detectable immunohistochemical or molecular evidence for MMTV was found in the liver specimens or PBLs. Conclusions: We were unable to recapitulate the data on this specific retroviral etiology of PBC and suggest that such data could be the result of contamination
Phylogenetic and immunological definition of four lipoylated proteins from Novosphingobium aromaticivorans, implications for primary biliary cirrhosis
No full textNovosphingobium aromaticivorans, a unique ubiquitous bacterium that metabolizes xenobiotics and activates environmental estrogens, has been suggested as a pathogenic factor in the development of primary biliary cirrhosis (PBC). To define the molecular basis of PBC sera reactivity, we investigated the characteristic of the bacterial antigens involved. We cloned and sequenced four genes from N. aromaticivorans coding for immunoreactive proteins, arbitrarily named Novo 1 through Novo 4. We subsequently analyzed these proteins for their homology to known mitochondrial proteins and defined their reactivity using monoclonal antibodies (mAbs), rabbit anti-lipoic acid antibody, and PBC/control sera. Moreover, we studied their phylogenetic relation with the known PBC autoantigens. Novo proteins have an extraordinary degree of amino acid homology with all of the major human mitochondrial autoantigens PDC-E2 (Novo 1 and 2), OGDC-E2 (Novo 3), and BCOADC-E2 (Novo 4). Moreover, Novo 1-4 contain a lipoylated domain, are recognized by AMA-positive sera, and react with specific mAbs to mitochondrial antigens. Interestingly, the phylogenetic relation of the proteins emphasizes the conservation of the lipoylated domain. In conclusion, our data provide a high degree of confidence that N. aromaticivorans may potentiate the breakdown of self tolerance in genetically susceptible individual
Horsemastership part 3: international perspectives of its therapeutic value
No full textIn previous opinion articles written by the authors, it has been proposed that horsemastership is an effective medium for therapy and education for young adults with additional needs. However, the existing research to support this proposal is informal and limited. Therefore, the first author carried out an international piece of research into the value of horsemastership to this group of people. A questionnaire using both quantitative and qualitative methods was completed by 21 professionals of various disciplines and countries who used horsemastership for therapeutic and educational purposes. This article gives a brief description of the methodology, including justification for the design selected, and discusses the relevance and implications of the results of this study. To pull together the three articles written by the authors, a final conclusion on the value of horsemastership to people with additional needs is drawn.<br/
A sensitive bead assay for antimitochondrial antibodies : Chipping away at AMA-negative primary biliary cirrhosis
No full textThe antimitochondrial response in primary biliary cirrhosis (PBC) is the most
highly directed and specific self-reacting antibody in human immunopathology.
Originally, antimitochondrial antibodies (AMAs) were detected by indirect
immunofluorescence (IIF) and found in approximately 90% of well-documented
patients with PBC. The introduction of recombinant autoantigens and the use of
immunoblotting have increased the sensitivity and specificity of AMAs, and they
are now considered positive in approximately 95% of patients with PBC. Clearly,
accurate autoantibody detection represents one of the fundamental requirements
for reliable diagnostics in autoimmunity. To address the 5% of AMA-negative
patients with PBC, we have generated and validated a bead assay for the detection
of AMA. We enrolled 120 patients with PBC, including a non-random group of 30
rigorously proven AMA-negative patients, 50 healthy subjects, and 74 controls
with autoimmune diseases (18 with primary sclerosing cholangitis, 16 with
autoimmune hepatitis, and 40 with systemic lupus erythematosus). Individual bead
assays were done with the three mitochondrial autoantigens, PDC-E2, BCOADC-E2,
and OGDC-E2. As expected, 90 of 90 previously known AMA-positive patients
remained positive with this assay but, interestingly, 20% of the rigorously
defined AMA-negative patient group had antibodies to one or more of the
mitochondrial autoantigens. Furthermore, 100% of these newly detected
AMA-positive patients were anti-nuclear antibody (ANA) positive. CONCLUSION: The
development of this assay reflects the potential for automated detection with
rapid and reliable assaying and further highlights the diminished number of truly
AMA-negative PBC patients
Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis
No full textThe role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (TLR) 2 (lipoteichoic acid; LTA), TLR3 (polyIC), TLR4 (lipopolysaccharide; LPS), TLR5 (flagellin), and TLR9 (CpG-B). Supernatant fluids from the cultures were analyzed for levels of 5 different pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, IL-12p70, and TNF-α. After in vitro challenge with TLR ligands, PBC monocytes produced higher relative levels of pro-inflammatory cytokines, particularly IL-1β, IL-6, IL-8, and TNF-α, compared with controls. In conclusion, monocytes from patients with PBC appear more sensitive to signaling via select TLRs, resulting in secretion of selective pro-inflammatory cytokines integral to the inflammatory response that may be critical in the breakdown of self-tolerance. Copyrigh
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