Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ah receptor regulates induction of cytochrome P450IA1 and mediates certain toxicities of polyhalogenated aromatics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been characterized previously in continuous cell lines, notably the mouse hepatoma line Hepa 1, the human squamous cell carcinoma line A431, and the human liver cell line Hep G2. The present work extends our knowledge of the Ah receptor in continuous human liver cell lines. Ah receptor can be detected in Mz-Hep-1, a hepatitis B virus-negative cell line derived from a Thorotrast-induced hepatocellular carcinoma. The mean concentration of Ah receptor in Mz-Hep-1 cells was 341 +/- 22 fmol/mg cytosol protein (mean +/- SEM, nine separate determinations). This is equivalent to approximately 30,000 sites per cell. The concentration of Ah receptor in Mz-Hep-1 cells is similar to that in Hepa 1 cells and approximately three times higher than that in Hep G2 cells. The Mz-Hep-1 Ah receptor sedimented in continuous sucrose gradients at approximately 9 S. Specificity of binding by [3H]TCDD was demonstrated by competitive binding of non-radiolabeled 2,3,7,8-tetrachlorodibenzofuran, 3-methylcholanthrene (MC), and dibenz[a,h]anthracene in 50-fold molar excess. Phenobarbital, which is not a substrate for P450IA1, did not compete with [3H]TCDD for binding to Mz-Hep-1 Ah receptor. Dexamethasone and estradiol also did not compete with [3H]TCDD for binding, suggesting non-identity of Ah receptor with glucocorticoid or estrogen receptor. In separate experiments, glucocorticoid receptor was identified in Mz-Hep-1 cells. By Scatchard plot analysis, the apparent equilibrium dissociation constant (Kd) for binding of [3H]TCDD to Mz-Hep-1 Ah receptor was estimated to be 4.4 nM, compared to 0.8 nM in Hepa 1 cells. By Woolf plot analysis the Kd was 5.4 nM, compared to 1.2 nM in Hepa 1 cells. The [3H]TCDD.Ah receptor complex extracted from nuclei of Mz-Hep-1 cells incubated with [3H]TCDD in culture at 37 degrees sedimented at approximately 6 S under conditions of high ionic strength. Aryl hydrocarbon hydroxylase (AHH) activity was detectable in Mz-Hep-1 cells after pretreatment with inducing chemicals. Mz-Hep-1 cells have the highest concentrations of Ah receptor in any continuous human liver cell line thus far investigated. The Mz-Hep-1 Ah receptor is similar physicochemically to that described in murine systems. AHH activity is inducible in Mz-Hep-1 cells.
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PMID:Ah receptor mediating induction of cytochrome P450IA1 in a novel continuous human liver cell line (Mz-Hep-1). Detection by binding with [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin and relationship to the activity of aryl hydrocarbon hydroxylase. 165 Feb 14

The effect of recombinant human erythropoietin (rHuEPO) on the immune system of hemodialysis patients has been studied by evaluating their response to hepatitis B (HB) vaccination. Fifty hemodialysis patients were given four doses of 20 micrograms recombinant DNA hepatitis B vaccine (SKF) at an interval of 0, 1, 2 and 6 months. Thirty-seven patients could be evaluated at one year. Twelve of 15 (80%) of the rHuEPO treated patients and 12 of 22 (54%) of non-rHuEPO treated dialysis patients developed anti-HBs antibodies. At the time of maximum immune response (8 months), the geometric mean anti-HBs titers (mIU/ml +/- SEM) of responders and all patients were five times (224.0 +/- 5.9 vs. 41.7 +/- 1.5, P less than 0.001), and eight times (57.6 +/- 8.7 vs. 6.7 +/- 1.8, P less than 0.05), respectively, higher in rHuEPO treated patients than in patients not receiving the drug. High antibody response (greater than 100 mIU/ml) prevailed in the group of rHuEPO treated patients and was associated with a high helper/suppressor ratio. Discriminant multivariate analysis (P = 0.038) revealed the influence of treatment with rHuEPO (40%) and helper/suppressor ratio (31%) on antibody concentration, while age, gender, duration of dialysis and previous blood transfusions were similar in both patient groups. Although changes in lymphocyte subsets observed in rHuEPO treated patients may be the result of a reduced administration of blood transfusions, immune reactivity seems also to be directly affected by the drug.
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PMID:Treatment with recombinant human erythropoietin increases antibody titers after hepatitis B vaccination in dialysis patients. 192 Nov 47

Children with uncontrolled autoimmune chronic active hepatitis have increased numbers of activated T lymphocytes expressing interleukin 2 receptors (IL2R). A soluble form of IL2R has recently been described whose proposed role is to downregulate T cell activation by competing for interleukin 2. We investigated whether a deficiency of soluble IL2R could account for the high concentrations of IL2R positive T lymphocytes in autoimmune chronic active hepatitis. Soluble IL2R was measured by enzyme-linked immunosorbent assay in the serum of 16 children with autoimmune chronic active hepatitis, eight with chronic liver disease due to hepatitis B virus infection, seven with Wilson's disease, nine with alpha 1 antitrypsin deficiency, and 15 healthy age matched controls. Soluble IL2R concentration was significantly higher in patients with autoimmune chronic active hepatitis than in healthy controls (mean (SEM) 475 (75) U/ml, 145 (8) U/ml respectively, p less than 0.01). Eleven patients who had active disease had significantly higher soluble IL2R concentrations (590 (89) U/ml) than the five cases with inactive disease (220 (36) U/ml, p less than 0.01). No difference was found between the controls and the patients with chronic liver disease due to hepatitis B infection, Wilson's disease, and alpha 1 antitrypsin deficiency. Percentages and absolute numbers of surface IL2R positive T cells as detected by immunofluorescence were significantly higher in the patients with autoimmune chronic active hepatitis (11.8% (1); 274/microliters (31)) than in controls (0.2% (0.1); 5/microliters (2), p less than 0.001), the highest values being found in those with uncontrolled disease. A significantly positive correlation was observed between concentrations of soluble IL2R and the percentage of T cells expressing IL2 receptors (r=0.67, p<0.001). These results indicate that the high levels of IL2R positive T lymphocytes characteristic of autoimmune chronic active hepatitis are not due to a deficiency of soluble IL2 receptors.
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PMID:Soluble interleukin 2 receptors in autoimmune chronic active hepatitis. 237 74

The mechanism responsible for liver cell necrosis in patients with hepatitis A is not known. Since the type of hepatic lesions and the clinical presentation of acute hepatitis B are similar and are probably related to the cell-mediated immune response to a viral antigen located in the liver cell, it is possible that a similar mechanism is involved in hepatitis A. In the present paper, immune reactivity to hepatitis A antigen (HAAg) was measured in 13 patients at the time of recovery from hepatitis A, by using the leukocyte migration inhibition test (LMIT) under agarose with purified HAAg as antigen. Eleven normal subjects without history of hepatitis and 4 patients convalescent from hepatitis B were used as controls. Inhibition of leukocyte migration by HAAg was found in 11 of the 13 patients, with an average migration index (MI) of 77.0% (SEM 3.5). No such inhibition was found in any of the controls: MI = 100.8% (SEM 1.0), P less than 0.0001. These findings show that, like for HBsAg in hepatitis B, an immune response specific for HAAg can be demonstrated by the LMIT after HAV infection. This response could perhaps be related to the liver injury associated to hepatitis A.
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PMID:A specific immune response to purified HA antigen (HAAg) demonstrated by leukocyte migration inhibition in patients recovering from viral hepatitis A. 300

To determine the effect of corticosteroids on the replication of hepatitis B virus and to assess the relationship between virus replication and prognosis, the behavior of serum and tissue HBcAg was evaluated in 16 patients with severe HBsAg-positive chronic active hepatitis who were treated with prednisone and followed for up to 10 years (mean +/- SEM, 66 +/- 9 months). Hepatitis B virus replication was assessed in serum by a solid-phase radioimmunoassay of Dane particle-associated HBcAg and in liver tissue by indirect immunoperoxidase staining for HBcAg. Despite the presence of severe inflammatory activity, only low levels of hepatitis B virus replication were demonstrated. Mean serum HBcAg levels were low at accession and remained essentially unchanged or gradually decreased during corticosteroid therapy. Serum HBcAg appeared in only one patient in whom no virus replication was detected prior to therapy. HBeAg was frequently detected at low titers by radioimmunoassay when serum HBcAg was undetectable. Loss of HBcAg preceded loss of HBeAg by radioimmunoassay, and disappearance of both markers was a prerequisite for sustained histologic remission. In eight patients, inflammation was present despite absence of serum or tissue HBcAg; in three of these, disease activity continued after loss of HBeAg. We conclude that low levels of hepatitis B virus replication may be associated with severe inflammatory activity, and these levels are not increased by long-term corticosteroid therapy. Inflammation can continue despite loss of HBeAg and absence of detectable virus replication.
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PMID:Hepatitis B virus replication in steroid-treated severe HBsAg-positive chronic active hepatitis. 396 68

Ultrastructural studies with the transmission (TEM) and scanning (SEM) electron microscopes have added greatly to our knowledge of cellular structure and function in the liver. The normal polyhedral hepatocyte has numerous subcellular organelles, such as mitochondria, peroxisomes, lysosomes and complex rough (rer) and smooth (ser) endoplasmic reticulum. The normal hepatocyte stores glycogen, and sometimes lipid droplets, and secretes bile through the bile canaliculi between adjacent liver cells. It receives nutrients from the sinusoidal lumen across a fenestrated endothelium which is separated by the Space of Disse' from the plasma membrane. The Space of Disse' contains a scant network of reticulin fibers but no basal lamina. Two types of parasinusoidal cells are found in Disse's space: the fat storing cells of Ito, and the Pit cells which may have an endocrine function. The diseased liver has yielded much information in studies with TEM and SEM. The studies with TEM have been most helpful in studying the etiology of infectious diseases such as hepatitis B; have revealed organelle changes such as megamitochondria in cirrhosis and the fibrillar nature of alcoholic hyaline; have led to the identification of specific deposits in metabolic and storage diseases such as hemochromatosis (iron). Wilson's disease (copper), and alpha-1-antitrypsin deficiency (glycoprotein) have proven useful in identifying drug induced liver cell changes such as proliferation of SER and cholestasis, and are useful for identifying specific cell types in inflammatory and neoplastic diseases. In the future, both TEM and SEM coupled with histochemical, cytochemical, immunohistochemical and other analytic techniques will continue to add greatly to our understanding of the liver in health and disease.
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PMID:Ultrastructure of the liver and biliary tract in health and disease. 637 90

Studies on the natural history of chronic type B hepatitis have shown that loss of hepatitis B e antigen and seroconversion to antibody to hepatitis B e antigen are usually accompanied by remission of disease activity and improvement in serum aminotransferase levels. Twenty-five symptomatic patients with biopsy-documented chronic type B hepatitis were followed for 25 +/- 2 mo (mean +/- SEM) after disappearance of hepatitis B e antigen, hepatitis B virus-deoxyribonucleic acid, and deoxyribonucleic acid polymerase activity from the serum. Twenty-four patients developed the antibody to hepatitis B e antigen. All 25 patients demonstrated a decrease in serum aminotransferase levels, and most became asymptomatic. However, during subsequent follow-up, 8 of the 25 patients (32%) exhibited reactivation of chronic type B hepatitis manifested by abrupt elevation of serum aminotransferase levels and reappearance of serum hepatitis B virus-deoxyribonucleic acid, deoxyribonucleic acid polymerase activity, and, in 7 patients, hepatitis B e antigen. All 8 patients developed symptoms: 3 became icteric, 3 developed ascites, and 2 bled from esophageal varices. One of these patients died. Episodes of reactivation invariably occurred within 1 yr of loss of hepatitis B e antigen and lasted for up to 13 mo. These observations suggest that loss of hepatitis B e antigen and seroconversion to the antibody to hepatitis B e antigen do not necessarily imply permanent remission of chronic type B hepatitis, and subsequent spontaneous reactivation may be an important cause of progression of hepatic injury.
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PMID:Spontaneous reactivation of chronic hepatitis B virus infection. 669 Mar 50

High-affinity monoclonal IgG and IgM antibodies to hepatitis B surface antigen (HBsAg) have been prepared and their functional capabilities explored by means of solid-phase radioimmunoassays. 125I-labeled HBsAg binding studies indicated that monoclonal IgM antibodies against HBsAg (anti-HBs) coupled to a solid-phase support quantitatively bound more HbsAg at a faster rate than conventionally prepared anti-HBs reagents or other high-affinity IgG monoclonal anti-HBs antibodies. Consequently, IgM anti-HBs was also radiolabeled, and an IgM-IgM radioimmunoassay was developed for the immunodiagnosis of hepatitis B. The lower limit of this assay was approximately 100 pg +/- 30 (SEM) of HBsAg per ml of serum. Compared to available commercial radioassays, preliminary studies have shown the IgM-IgM assay to have increased sensitivity, which improved the detection of a HBsAg-associated determinant in acute hepatitis and post transfusion hepatitis. It is probable that the multivalent interaction between monoclonal IgM anti-HBs and the polydeterminant HBsAg is important in augmenting the performance of this monoclonal assay.
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PMID:Immunodiagnosis of hepatitis B with high-affinity IgM monoclonal antibodies. 694 Jan 37

Active immunization is crucial for eradicating hepatitis B virus infection from dialysis units. A prospective study was performed in 63 consecutive chronic uremic patients, which included the following: (1) the intramuscular (IM) administration of 40 micrograms of a DNA-recombinant vaccine (Engerix-B, Smith Kline & French Laboratories, Milan, Italy) to all chronic uremic patients at 0, 1, 2, and 6 months; (2) the antibody titer determination at the seventh month (chronic uremic patients with a titer > 100 mIU/mL received an IM booster dose of 40 micrograms at 18 months [group A], and those with a titer < 100 mIU/mL received a further IM dose of 40 micrograms at 12 months [group B]); and (3) the intradermal inoculation of 5 micrograms of vaccine every 2 weeks until the protective titer (> or = 10 mIU/mL) was achieved, and then monthly for 6 months, in chronic uremic patients who did not have a protective titer even after 19 months (group C). Thus, 41, 17, and five chronic uremic patients were allocated to groups A, B, and C, respectively. All developed a protective titer: 79.4%, 84.0%, and 87.5% after the fourth, fifth, and sixth IM dose at 7, 13, and 19 months, respectively. Five chronic uremic patients (group C) achieved seroprotection after 3.8 +/- 0.5 (SEM) intradermal inoculations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatitis B virus infection in chronic uremia: long-term follow-up of a two-step integrated protocol of vaccination. 784 67

Sixty-five patients with haemophilia A from Singapore General Hospital, treated within the last 15 years exclusively with cryoprecipitate, were studied for the effect of the total number of exposures to random blood donors on their immune system. These haemophiliacs were aged 4 to 71 years (median 24 years) and were all apparently healthy with no clinical evidence of viral infection. None of them was a homosexual or intravenous drug user. All of them tested negative for human immuno-deficiency virus antibody and hepatitis B surface antigen. Analysis of the T-lymphocyte subset population showed 20 out of 65 haemophiliacs or 30.8% had reversal of T4/T8 ratio, ie. less than 1.00. There was no significant difference in the mean age of the 20 patients with abnormal T4/T8 ratios compared with the 45 with normal T4/T8 ratios. The mean age of the former group was 23 and the latter was 25. The group with reversal of T4/T8 ratio had exposure to 827.4 +/- 137.3 (mean +/- SEM) random blood donors, which is significantly higher than 402.5 +/- 64.1 in the group with normal T4/T8 ratio (p < 0.05). The reversal of T4/T8 ratio is predominantly due to the suppression of absolute T4 cell counts, with slightly raised absolute T8 cell counts. This abnormality may be transient or permanent. Interestingly, all the six out of 65 haemophiliacs with factor VIII inhibitor did not show any reversal of T4/T8 ratio in this study.
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PMID:Altered immunity in haemophiliacs treated exclusively with cryoprecipitate. 836 41


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