UMLS:C0019158 - FACTA Search

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Query: UMLS:C0019158 (hepatitis)
30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatitis-like changes were induced in the liver of albino female rats weighing 120-150 g and fed on the appropriate vivarium diet by single parenteral administration of hydrochloride galactosamine in a dose of 0.9 or 1.8 mmol per 1 kg of body weight. The thiamine diphosphate level in the cytosol fraction of the liver decreased 24 h after the preparation administration, the same in blood but with the higher dose used. The activity of pyruvate dehydrogenase, a thiamine diphosphate dependent enzyme, decreased similarly. The cytosol transketolase activity lowered by 38-39%. The coenzyme biosynthesis disturbance due to a fall by 49-58% in the thiamine pyrophosphatase activity is considered to be responsible for hydrochloride galactosamine-induced decrease in the thiamine diphosphate pool. Specificity of the thiamine diphosphate pool disturbance and discoordination of thiamine diphosphate dependent enzymes in the liver are observed under administration of hydrochloride galactosamine.
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PMID:[Thiamine diphosphate pool and its biosynthesis in the liver in galactosamine hepatitis]. 258 37

Autoantibodies are important diagnostic markers for autoimmune type chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). At least three subgroups of AI-CAH can be distinguished serologically. Antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and liver membrane autoantibodies (LMA) characterize classical autoimmune type 'lupoid' hepatitis, while liver kidney microsomal (LKM) antibodies identify a second, and antibodies to a soluble liver antigen (anti-SLA), a third subgroup of AI-CAH. Patients with autoimmune type CAH in contrast to patients with virus-induced liver diseases profit from immunosuppressive therapy. PBC is characterized by disease-specific subtypes of antimitochondrial antibodies (AMA). Technical developments, like immunoblotting and molecular cloning, led to a better definition and characterization of autoantibody-antigen systems. Molecular cloning has been successfully applied to identify the main 70 kDa mitochondrial antigen in PBC. This and other mitochondrial autoantigens have been identified as enzymes: E2 component of pyruvate dehydrogenase (PDH-E2) and its component X, branched chain alpha-keto acid dehydrogenase (BCKD-E2), and 2-oxoglutarate dehydrogenase. LKM-1 antigen has been identified as cytochrome P-450 db1, a drug metabolizing enzyme with a known genetic polymorphism. These cloned hepatic autoantigens share some characteristics with other autoantigens: they are enzymes, autoantibodies react with active sites of these enzymes and the autoepitopes are highly conserved. After the identification of these autoepitopes, specific and sensitive diagnostic reagents will become available. B and T cell epitope mapping will help to elucidate whether these autoantibodies are just clinically valuable diagnostic markers or whether they contribute to the immunopathogenesis or help to identify the aetiological agents.
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PMID:Autoantibodies and antigens in liver diseases--updated. 268 96

Trifluoroacetylated (CF3CO-) proteins, elicited upon exposure of animals or humans to halothane, were recognized by anti-CF3CO antibody, monospecific for the hapten derivative N6-trifluoroacetyl-L-lysine. Anti-CF3CO antibodies cross-reacted with the dihydrolipoamide acetyltransferase (E2 subunit) of pyruvate dehydrogenase, indicating that epitopes on the E2 subunit of pyruvate dehydrogenase molecularly mimic those on CF3CO-proteins. Lipoic acid, the prosthetic group of the E2 subunit of pyruvate dehydrogenase was essential in this process, in that only the lipoylated form of the recombinantly expressed inner lipoyl domain of the human E2 subunit of pyruvate dehydrogenase, but not the unlipolyated form, was recognized by anti-CF3CO antibody. Furthermore, based on a high degree of structural relatedness, both CF3CO-Lys and (6RS)-lipoic acid, as well as the lipoylated peptide ETDK(lipoyl)ATIG specifically inhibited the recognition by anti-CF3CO antibody of the E2 subunit of pyruvate dehydrogenase, of trifluoroacetylated rabbit serum albumin and of human liver CF3CO-proteins. In sera of patients with halothane hepatitis, autoantibodies with properties identical to those of anti-CF3CO antibody were identified which could not discriminate between CF3CO-proteins and the E2 subunit of pyruvate dehydrogenase. These data suggest that the E2 subunit pyruvate of dehydrogenase is an autoantigen in halothane hepatitis and that molecular mimicry of CF3CO-proteins by the E2 subunit of pyruvate dehydrogenase is due to the similar structures of CF3CO-Lys and lipoic acid.
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PMID:Identification of the dihydrolipoamide acetyltransferase subunit of the human pyruvate dehydrogenase complex as an autoantigen in halothane hepatitis. Molecular mimicry of trifluoroacetyl-lysine by lipoic acid. 751 86

A new non-linear mathematical model was constructed in order to perform in vivo quantification of the RES phagocytic function. This method is based on the same technical facilities as used for the routine liver-spleen scintigraphy with radiocolloids [1, 2]. But kinetic modeling of dynamic Tc-99m-sulfur colloid data produced estimations of the functional RE-parameters: the clearance rate of the colloidal particles, the rate of phagocytosis, and the RES functional volume, which can not be obtained by classical approaches. This non-linear model was designed on the basis of the principal characteristics of particulate material interaction with macrophages (attachment, phagocytosis, digestion) [3, 4, 5]. The theoretically examined behavior of this in vivo mathematical model corresponds with the experimental behavior of the RES. The mathematical expression of the dynamics is the system of non-linear differential equations with constant coefficients that have no analytical solution. Fitting of the normalized heart blood time-activity curve was obtained to identify the unknown model parameters via non-linear regression. For this purpose general interactive PASCAL procedure IDPAR for a PDP-11/34 computer was used (an IBM PC version is also available). Two to three iterations were needed to estimate the set of unknown parameters for any patient study (1-1.5 min). A very good fitting was obtained between experimental and model curves in every case of different pathologies (error of the approximation is about 2-3%). Studies were performed using an in vivo bolus injection of 3.6 mg/80 kg commercially available colloid KOREN labeled with 3m-Ci 99m-Tc (analog of TCK-1). Our method was used to determine the RES functional parameters for patient groups with different levels of the RES dysfunction. Obtained results illustrate the possibilities of our technique to quantitatively estimate not only great pathology (portal cirrhosis), but also small changes of the RE-function (case of hyperlipidemia and ulcer gaster). In all patient groups marked changes of Tc-99m-sulfur colloid turnover were observed. In general, tracer clearance from the circulation was decreased, and the rate of phagocytosis and the RES volume were diminished compared with controls. The effect of a reduction of phagocytosis increases when the RES dysfunction becomes stronger. It can be shown that a non-parametric Wilcoxon-Mann-Whitney test gives a significant difference (P95%) for these patient groups. Further, we represent the possibility of using the model for monitoring changes of the RES-function parameters during and after therapy. The quantitative test of the RES function can significantly enhance the diagnosis and management of different diseases. Serial colloidal studies may document changes in the RES-function for the tumors, cirrhosis, hyperlipidemia, reticulosis, hepatitis, thrombosis, infection, AIDS, burn injury, shock and trauma patients. The technique may be useful for the different RES investigations with laboratory animals. Created computer software can be used as a tool for kinetic models, simulation, and unknown parameters identification.
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PMID:A non-linear mathematical model for the in vivo evaluation of the RES phagocytic function. 859 76

Auto-antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched-chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti-LKM1 was also measured by indirect immunofluorescent test. Anti-P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH-C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non-B non-C (NBNC) and AIH were seronegative for anti-LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH-B. Anti-BCKD-E2 but not anti-PDH-E2 was found in four patients (2.5%), one with AIH, two with CH-C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti-SLA and anti-BCKD-E2. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 are uncommon in adult CH-C, CH-B, CH-NBNC and AIH patients in Japan. Some of these patients positive for auto-antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto-antibodies.
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PMID:Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis. 950 98

We report here a patient with chronic active hepatitis who had no markers for hepatitis viruses and no hyper-gamma-globulinemia, but had high titers of antimitochondrial antibody. Serum levels of alkaline phosphatase were normal, and antinuclear antibody, antismooth muscle antibody, and antiliver kidney microsome antibody tested negative. The titers of antimitochondrial antibody exceeded 1:640, and the positivity for anti-M2 was ascertained by using both ELISA and immunoblot with beef-heart mitochondria and a recombinant pyruvate dehydrogenase E2 subunit as antigens. This patient responded to ursodeoxycholic acid (UDCA) therapy in the beginning, but her hepatitis flared up during UDCA therapy. In contrast, she responded completely to corticosteroid therapy. The clinical course and histological findings of this patient strongly suggest that this patient has autoimmune hepatitis.
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PMID:A case of autoimmune hepatitis with a high titer of antimitochondrial antibody and normal gamma-globulinemia. 1144 97

The differential diagnosis of the three disorders that are usually classified as autoimmune liver diseases, namely autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), requires careful exclusion of other causes of chronic liver disease together with the finding of suggestive patterns of abnormalities of serum biochemical parameters, immunoglobulin isotypes and 'conventional' non-organ-specific autoantibodies. Antimitochondrial antibodies (particularly those reacting with epitopes on the E2 components of the pyruvate dehydrogenase and other 2-oxo-acid dehydrogenase complexes), and some sub-specificities of antinuclear antibodies, are virtually pathognomonic of PBC. Anti-liver-kidney microsomal antibodies reacting with defined epitopes on the cytochrome isoform P4502D6 are relatively specific for a small sub-group of (so-called 'type 2') AIH. However, most of the other serological parameters lack specificity. Additionally, within and between each disease group there is wide variability, even among patients with comparable severity of liver damage. Thus, in many cases, liver histology and/orcholangiography is still required for definitive diagnoses or for assessing stage and severity of these disorders. A number of autoantibodies that are more directly related to the liver than the 'conventional' autoantibodies are showing promise as possibly more specific diagnostic markers of AIH. Commercial tests for some of these are under development and it is hoped that they will soon become widely available.
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PMID:Autoimmune liver diseases. 1171 93

Autoimmune diseases of the liver are chronic inflammatory diseases leading to an etiologically undefined immune-mediated attack aimed at the hepatocyte, small microscopic bile ducts, and the entire biliary system detectable by cholangiography, respectively. From the standpoint of clinical disease three entities can be distinguished: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). These are not only different regarding their clinical profile but also differ in diagnostic strategy, therapeutic regimen and probability of remission, as well as their association with other immune-mediated diseases and cancer. PBC and PSC are cholestatic diseases. PBC is most often diagnosed in women. The diagnosis is readily reached by the detection of specific antimitochondrial autoantibodies directed against pyruvate dehydrogenase (PDH-E2), is associated with an array of rheumatological extrahepatic syndromes and responds unsatisfactorily to immunosuppressive drugs. Ursodeoxycholic acid leads to biochemical and possibly histological benefits. In contrast, PSC affects younger men who suffer from inflammatory bowel disease in 75% of cases. PSC is not characterized by specific serum autoantibodies. The diagnosis is reached by histology and typical findings upon cholangiography. In 10-20% PSC is associated with cholangiocarcinoma and also with colon cancer. PSC also does not respond well to immunosuppression. Therapeutic interventions include mechanical endoscopic manipulation of the bile ducts, treatment of cholangitis and ursodeoxycholic acid. AIH is a classical autoimmune disease with a female predisposition, circulating autoantibodies, elevated immunoglobulins, the association of other extrahepatic autoimmune diseases, and a dramatic response to immunosuppression with normalization of the patient's prognosis upon remission and prevention of cirrhosis. However, the diagnosis is only reached by the exclusion of other liver diseases also characterized by biochemical, histological and clinical features of chronic hepatitis. In this light, the precise diagnosis is essential. In spite of the clear distinctions of the three diseases overlapping syndromes do exist. These can be characterized as the coexistence of serological parameters of PBC and AIH, of cholestasis and hepatitis, of autoantibodies and viral markers, or the consecutive manifestation of PBC and AIH, or AIH and PSC. However, the overlap of genuine autoimmune diseases is rare. This is relevant regarding therapy and must lead to the precise clinical and diagnostic discrimination of serological autoimmunity (autoantibodies) and genuine autoimmune disease (i.e. AIH) for the initiation of efficatious therapeutic measures. AIH, PBC and PSC are well established indications for liver transplantation with good results. Transplantation is required when cirrhosis is progressive despite therapy and is likely to lead to liver failure.
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PMID:[Autoimmune liver diseases and their overlap syndromes]. 1698 80

Antimitochondrial antibodies (AMA) are the serum hallmark of primary biliary cirrhosis (PBC). However, AMA-positivity can be found in non-PBC sera when lower dilutions are used, thus raising issues about the specificity and sensitivity of the test. AMA reacts primarily with the lipoylated domains of pyruvate dehydrogenase-E2 (PDC-E2) which is highly conserved across species, including bacteria. We studied 77 serum samples, including 24 from patients with anti-PDC-E2-positive PBC and 53 controls (16 with autoimmune hepatitis (AIH), 10 with primary sclerosing cholangitis (PSC), and 27 healthy individuals) for their reactivities at serial dilutions (1:10, 1:20 and 1:40) against Escherichia coli DH5 alpha lysate overexpressing human PDC-E2 using immunoblotting (IB). A murine anti-human PDC-E2 monoclonal antibody (mAB) was used as control. We further studied positive sera using adsorption with a synthetic E. coli peptide sharing similarity with human PDC-E2. Finally, we verified whether a unique buffer for E. coli preparation could reduce non-specific serum reactivity. Results demonstrated that 100% of anti-PDC-E2-positive PBC and up to 38% of control sera at 1:10 dilution recognized E. coli PDC-E2 at IB while dilution tests indicated that the overall potency of PBC reactivity was 100-fold higher compared to controls. In fact, a subgroup (20-38%) of non-PBC sera were positive at low titers but lost the reactivity when absorbed with the synthetic E. coli peptide. Finally, our unique buffer reduced the reactivity of non-PBC sera as measured by ELISA. In conclusion, we demonstrated that weak cross-reactivity with E. coli PDC-E2 occurs in non-PBC sera at lower dilutions and that such reactivity is not due to AMA-positivity. The use of a specific buffer might avoid the risk of false positive AMA determinations when E. coli-expressed recombinant antigens are used.
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PMID:Serum reactivity against bacterial pyruvate dehydrogenase: increasing the specificity of anti-mitochondrial antibodies for the diagnosis of primary biliary cirrhosis. 1716 70

Metabolic reprogramming is implicated in macrophage activation, but the underlying mechanisms are poorly understood. Here, we demonstrate that the NOTCH1 pathway dictates activation of M1 phenotypes in isolated mouse hepatic macrophages (HMacs) and in a murine macrophage cell line by coupling transcriptional upregulation of M1 genes with metabolic upregulation of mitochondrial oxidative phosphorylation and ROS (mtROS) to augment induction of M1 genes. Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. As such, inhibition of the NOTCH pathway or Pdp1 knockdown abrogated glucose oxidation, mtROS, and M1 gene expression. Conditional NOTCH1 deficiency in the myeloid lineage attenuated HMac M1 activation and inflammation in a murine model of alcoholic steatohepatitis and markedly reduced lethality following endotoxin-mediated fulminant hepatitis in mice. In vivo monocyte tracking further demonstrated the requirement of NOTCH1 for the migration of blood monocytes into the liver and subsequent M1 differentiation. Together, these results reveal that NOTCH1 promotes reprogramming of mitochondrial metabolism for M1 macrophage activation.
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PMID:NOTCH reprograms mitochondrial metabolism for proinflammatory macrophage activation. 2666 11

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