Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver-derived lymphocytes were isolated from 73 liver biopsy specimens obtained from patients with chronic active liver disease and from six samples of normal liver. Mean absolute numbers (+/- S.E.M) of liver-derived lymphocytes recovered from needle biopsy specimens by mild enzymatic digestion of the liver tissue varied from 0.7 +/- 0.3 x 10(3)/mm3 in allografts being rejected to 8.9 +/- 0.9 X 10(3)/mm3 in chronic non-A, non-B hepatitis. By two-color flow cytometry, T lymphocytes (CD3+) were the major liver-derived lymphocyte population in all biopsy specimens. The mean CD4/CD8 ratio (0.6 +/- 0.2) was similar for liver-derived lymphocytes obtained from samples of normal or diseased liver. However, activated (human leukocyte antigen DR+) T cells were significantly (p less than 0.05) increased in liver-derived lymphocytes obtained from liver disease specimens than they were in samples from normal livers. Natural killer cells were less numerous than T cells in specimens obtained from diseased livers, with the mean natural killer/T cell ratio ranging from a low of 0.1 in allograft rejection to a high of 0.8 +/- 0.3 in primary sclerosing cholangitis. Liver-derived lymphocytes isolated from diseased liver contained significantly fewer (p less than 0.05) CD3-CD56+ or CD56+CD16-natural killer cells than did those obtained from normal liver samples. Natural killer activity was consistently detectable in liver-derived lymphocytes obtained from specimens of normal or diseased livers. Moreover, natural killer activity in the liver did not differ significantly from that in either normal or patient peripheral blood.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phenotypic and functional characteristics of lymphocytes isolated from liver biopsy specimens from patients with active liver disease. 156 23

We investigated the effects of interferon therapy on hepatocyte human leukocyte antigen class I and class II antigen expression and intrahepatic lymphocyte subsets in patients with chronic viral hepatitis B (n = 11) and C (n = 10). Interferon-alpha was administered intramuscularly in doses ranging from 3 to 18 million international units daily for 4 wk. Liver biopsy specimens were obtained just before and immediately after treatment, and the specimens were stained by the indirect immunoperoxidase method for evaluation of human leukocyte antigen expression and lymphocyte subsets. Before therapy, no significant difference was noted between hepatitis B and C in human leukocyte antigen class I antigen expression on hepatocytes or in the lymphocyte subsets in the intralobular and portal areas. After interferon-alpha treatment, hepatocyte expression of human leukocyte antigen class I antigens and serum beta 2-microglobulin levels were virtually unchanged in chronic viral hepatitis C patients, but both were increased in chronic viral hepatitis B patients. Human leukocyte antigen class II antigens were not expressed during treatment. The mean number of intralobular CD3+ and CD8+ cells and the mean serum ALT level decreased significantly in chronic viral hepatitis C patients (p less than 0.05) but not in chronic viral hepatitis B patients. The mean number of intralobular CD4+ cells was unaffected by interferon therapy in both groups. In all 21 patients, the changes in CD8+ cell numbers paralleled the changes in serum ALT levels. Our findings suggest that T-cell cytotoxicity may play an important role in hepatocyte damage in both chronic viral hepatitis C and chronic viral hepatitis B and that the response to interferon-alpha differs in these two types of hepatitis.
 ...
PMID:Effects of interferon on intrahepatic human leukocyte antigens and lymphocyte subsets in patients with chronic hepatitis B and C. 171 Oct

To identify prognostic features and to define the role of liver transplantation in severe autoimmune chronic active hepatitis, findings before and after corticosteroid therapy in 111 patients were correlated with outcome and compared with the findings in 24 patients who had been selected independently for liver transplantation. Patients whose condition deteriorated during corticosteroid treatment were younger (32 +/- 3 yr vs. 43 +/- 2 yr; p less than 0.02) than those who experienced remission, but no individual features predicted outcome. Patients in whom therapy failed required longer durations of continuous treatment than did those who experienced remission (60 +/- 14 mo vs. 20 +/- 12 mo; p = 0.001). Of 13 patients who did not experience remission within 4 yr, 9 (69%) ultimately deteriorated. Ascites developed more often in those patients whose therapy failed and who died of liver failure than in counterparts who survived (86% vs. 33%). Patients undergoing transplantation were similar to those whose treatment failed, but they died less frequently (8% vs. 56%, p less than 0.01). Indeed, the 5-yr survival rate after transplantation was comparable to that of patients who had entered remission (92% vs. 100%). Successive biopsy samples failed to disclose recurrent autoimmune hepatitis after transplantation. Human leukocyte antigens A1, B8 occurred more commonly in patients in whom treatment failed or who underwent transplantation (70% vs. 41%, p less than 0.05). We conclude that failure to achieve remission within 4 yr and the human leukocyte antigen A1, B8 phenotype are associated with poor prognosis. Manifestations of liver decompensation, such as ascites, in patients who have been unable to experience remission justify consideration of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prognostic features and role of liver transplantation in severe corticosteroid-treated autoimmune chronic active hepatitis. 1100 37

Human leukocyte antigen-D region-related alleles (human leukocyte antigen DR and DQ) and human leukocyte antigen class I alleles were typed serologically in 31 Japanese patients with autoimmune hepatitis. These patients had increased serum levels of AST and IgG, high titers of autoantibodies, no history of blood transfusion and were negative for HBsAg and antibodies to HBc. Three hundred eighty-six healthy subjects and 30 patients with cryptogenic chronic hepatitis served as control groups. The frequency of DR4 was significantly higher in autoimmune hepatitis patients (90.3%) than in healthy subjects (38.6%) and in cryptogenic chronic hepatitis patients (30%). The frequency of Bw54 was significantly higher in autoimmune hepatitis patients (45.2%) than in healthy subjects (10.9%). The risk to DR4-positive subjects for autoimmune hepatitis was 14.8 relative to healthy subjects. Two of 31 patients (6.5%) with autoimmune hepatitis were positive for antibody to hepatitis C virus; both clearly satisfied criteria for autoimmune hepatitis and both had Bw54 and DR4. This study revealed a highly significant association of autoimmune hepatitis with human leukocyte antigen Bw54 and DR4 in Japanese patients. Among the DR4-positive patients with autoimmune hepatitis, no significant differences were seen between those positive or negative for Bw54 with regard to clinical or laboratory data, relapse of disease or efficacy of prednisolone. Thus human leukocyte antigen class II alleles contribute to susceptibility and resistance to autoimmune hepatitis in Japanese patients, with distinct racial differences from those in white patients.
 ...
PMID:Association of autoimmune hepatitis with HLA-Bw54 and DR4 in Japanese patients. 217 92

A case of porphyria cutanea tarda (PCT) occurring after bone marrow transplantation (BMT) is reported. A 43-year-old male with chronic myelogenous leukemia received an human leukocyte antigen (HLA)-identical allogeneic transplantation with T-cell depleted marrow. Because of graft rejection, a second transplant was performed 4 months later. A grade II acute graft- vs.-host disease and a cytomegalovirus (CMV) infection were subsequently observed. Two years after the second transplant, cutaneous symptoms of PCT with typical biochemical abnormalities developed. Liver biopsy revealed signs of hepatitis with iron overload. CMV was isolated from liver tissue. The possible roles of underlying disease, BMT, and CMV liver disease are discussed in view of the recently reported cases of PCT in patients with AIDS or hematological disorders.
 ...
PMID:Porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukemia. 232 8

To study the role of antigen-specific T lymphocytes in the pathogenesis of autoimmune hepatitis, messenger RNA of T-cell receptors (TCR) was analyzed in liver biopsy specimens from four patients with autoimmune hepatitis. Using the TCR beta-chain variable region family specific oligonucleotides, a remarkable bias for the usage of beta-chain variable region 3 was detected in all four patients. Therefore, nucleotide and amino acid sequences of the complementarity-determining region 3 rearranged to the beta-chain variable region 3, which is a putative contact site for peptide fragments from antigens bound in the groove of the human leukocyte antigen molecule, was further analyzed in randomly selected 10 clones from each patient. An Asp-Arg-Pro motif in the complementarity-determining region 3 was identified in three of four patients with human leukocyte antigen DR4, and this motif was always rearranged to the beta-chain junctional region 1.2. From these results, beta-chain variable region 3+, Asp-Arg-Pro+, beta-chain junctional region 1.2+ T-cell clones may be among the responsible lymphocytes involved in the liver damage in autoimmune hepatitis, especially in patients with human leukocyte antigen DR4. Thus, an analysis of the complementarity-determining region 3 may give us an important clue to clarify characteristics of target antigens included in autoimmune hepatitis.
 ...
PMID:Limited usage of T-cell receptor beta chains and sequences of the complementarity determining region 3 of lymphocytes infiltrating in the liver of autoimmune hepatitis. 760 6

To determine the nature and prognostic implications of autoimmune hepatitis with an acute presentation, 12 patients with a disease duration of 3 months or less (mean duration, 2.3 +/- 0.2 months) were compared to 14 patients with a disease duration of 12 months or more (mean duration, 15.1 +/- 0.9 months). Liver tissue specimens were graded under code for lobular, portal and architectural changes. Patients with acute and chronic presentations were indistinguishable by age, sex, human leukocyte antigen phenotype, immunoserologic markers, and biochemical indices of liver inflammation. Moderate to severe lobular hepatitis was present more frequently in patients with acute presentations (75% versus 29%, p = 0.2), but differences were not statistically significant. Bridging fibrosis and cirrhosis were seen with equal frequency in both groups (79% versus 73%). Remission, relapse, treatment failure, progression to cirrhosis, and death from hepatic failure occurred with similar frequencies in patients with acute and chronic presentations. We conclude that autoimmune hepatitis with an acute presentation is indistinguishable by clinical and laboratory features from that with a chronic presentation and it is probably a pre-existent subclinical disease that is unmasked by disease progression or an abrupt exacerbation. Lobular hepatitis is an important histologic feature regardless of disease duration. The response to corticosteroid therapy is unaffected by the perceived duration of disease prior to treatment.
 ...
PMID:The nature and prognostic implications of autoimmune hepatitis with an acute presentation. 789 Sep 4

The dual observations that human leukocyte antigens have an antigen-binding groove and that the polymorphism we study as human leukocyte antigen types is largely related to amino acid substitutions in and around that groove have provided a new focus for immunogenetic studies. In autoimmune liver disease, recent studies have described specific amino acid substitutions in the antigen-binding groove of human leukocyte antigen DR molecules that may determine both disease susceptibility, through their direct influence on antigen binding, and the severity of the disease. In autoimmune hepatitis, lysine residues at DR beta position 71 in European subjects and arginine or histidine residues at DR beta position 13 in Japanese subjects may be responsible for much human leukocyte antigen-encoded disease susceptibility. Similar claims have been made for leucine residues at DR beta 38 in primary sclerosing cholangitis and for leucine residues at DP beta 35 in Japanese patients with primary biliary cirrhosis. To date, our knowledge of genetic susceptibility to autoimmune liver disease is incomplete. Other genes may contribute to susceptibility to autoimmune liver disease--for example the contribution of TAP genes, upstream promoter sequences and class III genes on chromosome 6 and the T-cell receptor genes and complement genes elsewhere in the human genome is currently unclear. Additional information concerning the immunogenetic contribution to disease severity is needed to complete the picture.
 ...
PMID:The molecular genetics of autoimmune liver disease. 802 Aug 93

We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlymphocytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; chi 2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; chi 2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (chi 2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis. 818 67

Major histocompatibility complex class II deficiency (bare lymphocyte syndrome) is a rare primary immunodeficiency disorder characterized by profound defects in human leukocyte antigen class II expression, inconsistent and incomplete expression of human leukocyte antigen class I molecules, and a complete lack of cellular and humoral immune responses to foreign antigens. To define the clinical and immunologic characteristics, outcome, and natural history of major histocompatibility complex class II deficiency, we retrospectively analyzed 30 consecutive patients. Clinical onset occurred in the first year of life, usually involving recurrent bronchopulmonary infections and chronic diarrhea. The clinical course was complicated by viral meningoencephalitis, hepatitis, cholangitis, and various autoimmune phenomena. Prognosis was very poor: the mean age at the time of death was 4 years. The main cause of death was overwhelming viral infection. Recent advances in bone marrow transplantation have raised hopes of curative treatment: 6 of 14 patients who underwent bone marrow transplantation were cured. Long-term survival after human leukocyte antigen-identical and haploidentical bone marrow transplantation seemed to depend primarily on the presence of preexisting viral infections.
 ...
PMID:Major histocompatibility complex class II deficiency: clinical manifestations, immunologic features, and outcome. 822 25


1 2 3 4 5 6 7 8 Next >>