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

Hepatocyte growth factor (HGF) is the most potent mitogen for mature hepatocytes and seems to act as a hepatotropic factor that has not been purified over the past 30 years. HGF was first purified from rat platelets in 1986. HGF is a hetrodimer molecule composed of 69-kDa alpha-subunit and 34-beta-subunit. In 1989, cDNAs of both human and rat HGF were cloned and primary structure of HGF was determined. HGF is derived from preproprecursor of of 728 amino acids, which is proteolytically processed to form mature HGF. The alpha-chain contains four kringle domains and it has 38% homology with plasmin. HGF mRNA and HGF activity increase markedly in the liver of rats after various liver injuries such as hepatitis, ischemia, physical crush, and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells and sinusoidal endothelial cells, but not in parenchymal hepatocytes. HGF mRNA is also markedly increased even in the intact lung, kidney, and spleen after injuries of the liver. Therefore, HGF may act as a trigger for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, HGF mRNA increases markedly in the kidney after various renal injuries, thus it suggests that HGF may act not only as a hepatotropic factor but also as a renotropic factor. HGF receptor with a Kd of 20 to 30 pM is widely distributed in various epithelial cells including hepatocytes. HGF receptor was recently identified as the product of c-met protooncogene, which encodes a 190-kDa transmembrane protein possessing tyrosine kinase domain. HGF has recently been shown to be a pleiotropic factor. HGF stimulates growth of various epithelial cells, including renal tubular cells (Mitogen). It is worth noting that HGF strongly enhances motility of epithelial cells (Motogen) and induces epithelial tubule formation (Morphogen), while it strongly inhibits growth of several tumor cells. All these findings indicate that HGF may have important roles in organogenesis, morphogenesis, carcinogenesis, as well as in organ regeneration.
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PMID:Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions. 131 69

Clinical, animal, and epidemiologic evidence indicates that exogenous steroids influence the risk of hepatocellular carcinoma (HCC) and a recent study suggested that parity also may increase the risk of this tumor in women. The latter hypothesis was evaluated in the data from a case-control study which was carried out in Athens and covered 166 male and 19 female cases of HCC, and 381 male and 51 female hospital controls. Among males, there was no association between the number of liveborn children and risk of HCC, whereas among women, there was a suggestive positive association. Compared with women with one or two children, the relative risk for HCC was 0.6 among nulliparous women, 1.3 among those with three or four children and 1.7 among those with five or more children. The association of parity with risk of HCC was limited to women who were positive for hepatitis-B surface antigen (HBsAg) and was not confounded by hepatitis-C virus infection or tobacco smoking. The small number of HCC cases does not permit firm conclusions. If confirmed, however, these results would provide the foundation for a practical preventive advice that could be given to women who are positive for HBsAg.
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PMID:Liveborn children and risk of hepatocellular carcinoma. 131 8

In persistent hepadnavirus infections, a distinctive feature of woodchuck hepatitis virus (WHV) is the coupling of frequent viral integrations into myc family genes with the rapid onset of primary liver tumors. We have investigated the patterns of WHV DNA insertion into N-myc2, a newly identified retroposed oncogene, in woodchuck hepatomas resulting from either natural or experimental infections. In both cases, integrated viral sequences were preferentially associated with the N-myc2 locus. In more than 40% of the woodchuck tumors analyzed, viral insertion sites were clustered in a 3-kb region upstream of N-myc2 or in the 3' noncoding region. Insertion of WHV sequences homologous to the human hepatitis B virus enhancers, either upstream or downstream of the N-myc2 coding domain, was associated with the production of normal N-myc2 mRNA or hybrid N-myc2-WHV transcripts, initiated at the normal N-myc2 transcriptional start site. Transient-transfection assays with different N-myc2-WHV constructs in HepG2 cells demonstrated that the viral enhancers could efficiently activate the N-myc2 promoter. These results, showing that cis activation of preferred cellular targets through enhancer insertion is a common strategy for tumor induction by WHV, emphasize the previously noted similarities between hepadnaviruses and nonacute oncogenic retroviruses.
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PMID:Hepadnavirus integration: mechanisms of activation of the N-myc2 retrotransposon in woodchuck liver tumors. 132 93

The purpose of this study was to retrospectively analyse the results of 1102 primary liver cancer (PLC) patients who underwent liver resection in the past thirty years and to research some effective approaches for improving the longterm effect of PLC treatment. Ninety five percent were hepatocellular carcinoma (HCC), 85.2% with cirrhosis of hepatitis and 25.6% with tumor equal to or smaller than 5 cm in diameter. The mortality rate (MR) within 1 month after operation was 1.8%, the operative MR was 8.8% before 1977 and only 0.4% after that. The total 5-year survival rate (SR) was 28.4% while in the group of small tumor (less than or equal to 5 cm), it was 75.0%. Our experience is as follows: (1) Early diagnosis and early resection of PLC is the key point for improving the operative result of long-term survival. In 282 cases of small cancer, tumor resection rate was 90.0%. Of 48 cases with tumor equal to or smaller than 3 cm in diameter, the 5-year SR was 83.3%. (2) Rehepatectomy for recurrent liver cancer is an important approach for improving the surgical result. In our series, recurrent rate within 5 years postoperation was 72.3% in larger tumor group and 34.5% in small tumors. There were 78 cases undergoing reoperation in a total number of 170 times of rehepatectomy with 54.7% of 5-year SR, after the 1st operation and 34.6% after the 2nd one. (3) For unresectable large tumors, two-stage operation is an important development in liver surgery. We had 26 cases of such patients with 60.0% of 5-year SR. (4) Improvement of operating techniques plays an important role in reducing postoperative complications, lowering operative mortality and obtaining better operative result. (5) Postoperative comprehensive treatment is also important for solidating operative effect and preventing tumor recurrence.
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PMID:Surgical approaches for improving the operating results of primary liver cancer. 132 42

In order to clarify the significance of mutation of the p53 tumor suppressor gene in the genesis and development of human hepatocellular carcinoma (HCC) in an aflatoxin B1 low-exposure area, the spectrum, i.e., incidence, type, and site, of p53 gene mutations was examined in 169 tissue samples resected mainly from Japanese patients using single-strand conformation polymorphism analysis and direct sequencing. Forty-nine tumors (29%) showed a p53 mutation (39 point mutations and 10 frameshifts). The point mutations comprised 18 transitions, only 4 of which occurred at CpG sites, and 21 transversions. Two evolutionarily conserved domains, IV and V, contained 65% of all mutations and codon 249 was the most frequent mutation site (7/49). The spectrum of p53 mutation did not differ among HCCs in relation to the type of hepatitis virus infection, sex, age, and background liver disease of patients, tumor size, or presence of metastasis, but incidence and site were significantly associated with the degree of differentiation of cancer cells. In poorly differentiated HCC, p53 mutation was frequent (54%) and clustered on domains IV and V, whereas in well or moderately differentiated HCC, the mutation was less frequent (21%) and equally distributed on domains II to V. Restriction fragment length polymorphism analysis revealed loss of heterozygosity on chromosome 17p in 55 (69%) of 80 informative cases and in 34 (95%) of 36 cases with p53 mutation. Therefore, p53 gene mutation is suggested to occur independently of the type of viral infection or status of preexisting liver disease and to occur preferentially in moderately and poorly differentiated HCCs in association with or after loss of another p53 allele as a late event of HCC progression.
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PMID:p53 gene mutation spectrum in hepatocellular carcinoma. 133 Feb 91

A 15-year old Black teenager came to a clinic at the University of Alabama's School of Medicine in Tuscaloosa requesting oral contraceptives (OCs). The physical examination indicated that she was in good health and the physician prescribed an OC (1 mg norethindrone and .035 mg ethinyl estradiol). 21 months later she returned complaining of yellow eyes for 3 weeks. The oral mucosa was also jaundiced. She had considerably high levels of bilirubin and alkaline phosphatase. She had no hepatitis virus antibodies. 5 months later she returned for the physical examination required to renew the OC prescription. She did not have jaundice at this time. 10 months later she complained of malaise and muscular pain. Her alkaline phosphatase level was high, but her bilirubin level was normal. She had mild hepatosplenomegaly without focal defects. After reviewing her medical records, the physician diagnosed intrahepatic cholestasis and discontinued her OC prescription. Liver function tests were normal within 3 months. 14 months later, she returned complaining of malaise and reported taking OCs obtained at another clinic 3 months earlier. The physician advised her about the complications of OCs and about other contraceptive methods. The same physician also examined a 32-year-old Black woman who had intermittent epigastric and right-upper quadrant abdominal pain for 2 weeks. Eating worsened the pain, which lasted for up to 15 minutes. She had used an OC for 12 years. Ultrasound revealed a 4.2 cm hypoechoic mass in the left upper lobe of the liver. The physician discontinued the OCs. The tumor regressed over 12 months. Active liver disease is a contraindication to OC use. Women who had cholestatic jaundice while pregnant or have first degree relatives with cholestatic jaundice of pregnancy should not use OCs. Physicians may introduce OCs to closely monitored women with a history of liver disease whose liver function tests are normal. Women with a family history of biliary excretion defects should not use OCs.
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PMID:Hepatobiliary complications of oral contraceptives. 133 97

We report two cases of liver cell adenomatosis associated with granulomatous hepatitis, both developed in white women (52 and 39 years of age) on long-term oral contraceptives (for 18 and 12 years, respectively). The first patient underwent surgery for five hepatic tumors 1-7 cm in diameter; the other patient had a partial segmentectomy for a 4-cm hepatic nodule of the right lobe. In both cases, dissection of the liver showed many other diffuse and smaller nodules. Histologically, all tumors were benign liver cell adenomas, with cellular atypia in the largest tumor and associated in both cases with granulomatous hepatitis, with numerous noncaseating epithelioid and giant cell granulomas located either only in the tumors (case 1) or diffusely in the tumoral and nontumoral hepatic parenchyma (case 2). During follow-up, ultrasound showed new nodular lesions in case 2, whereas in case 1 evolution was uneventful. In estroprogestative-associated liver diseases, adenomas are common, but adenomatosis and granulomas are rare. An association of these latter two conditions would seem to be exceptional. The prognosis for adenomatosis remains uncertain.
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PMID:Liver adenomatosis with granulomas in two patients on long-term oral contraceptives. 135 95

The prevalence of hepatitis B and C virus infections was studied in 70 patients diagnosed as having hepatocellular carcinoma. In addition to viral serological markers, serum hepatitis B virus DNA and hepatitis C virus RNA were determined with a nested polymerase chain reaction assay. Twelve patients (17%) were HBsAg positive, 26 (37%) had antibodies to HBs, HBc or both and 32 (46%) were negative for all hepatitis B virus serological markers. Prevalence of the antibody to hepatitis C virus was 63% (44 patients). Hepatitis B virus DNA was detected in 24 of the 66 tested patients (36%). Twelve of these hepatitis B virus DNA-positive patients were HBsAg negative (seven were positive for antibody to HBs, antibody to HBc or both and five were negative for all hepatitis B virus serological markers). Hepatitis C virus RNA was found in 42 of 68 patients (62%). A high correlation (95%) existed between hepatitis C virus RNA and hepatitis C virus antibodies. Nevertheless, two patients without antibody to hepatitis C virus had serum hepatitis C virus RNA sequences. Coinfection by the two viruses was detected in nine subjects (14%), but no clinical differences were found between these and the rest of the patients. We conclude that nearly 90% (62 of the 70 patients studied) of cases of hepatocellular carcinoma in our geographical area are related to hepatitis virus infections (detected by serological or molecular studies). Hepatitis C is more prevalent than hepatitis B virus in patients with hepatocellular carcinoma, and the infection is still active when the tumor is diagnosed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatitis B and C viral infections in patients with hepatocellular carcinoma. 138 Apr 80

We measured urinary levels of free L-fucose in healthy subjects, patients with benign diseases, and patients with cancer using an automated analyzer and a newly isolated L-fucose dehydrogenase, and evaluated the clinical usefulness of the results. The values obtained were corrected for urinary creatinine as micromoles per gram of creatinine. The cutoff value, set at the mean + 2SD for the healthy subjects, was 250 mumol/g.Cr. Patients with gallbladder cancer, bile-duct cancer, liver cancer, pancreatic cancer, or cirrhosis of the liver had significantly higher levels of L-fucose than the healthy subjects. The diagnostic sensitivity for these five diseases, taken together, was 68% (144/213). Specificity for the detection of cancer was calculated by use of false positives for patients with cholelithiasis, hepatitis, and pancreatitis: it was 73% (76/104). Diagnostic accuracy for these seven diseases taken together was therefore 69% (220/317). We compared the positive ratio of the L-fucose level with that of the tumor markers AFD and CA19-9. The positive ratio of an L-fucose value above the cutoff was higher than the positive ratio of either marker in bile-duct cancer, gallbladder cancer, liver cancer, and pancreatic cancer. The results suggested that the urinary levels of free L-fucose reflected the metabolism of sugar chains of glycoconjugates, and may be usefully clinically as a tumor marker.
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PMID:[Clinical assessment of urinary free L-fucose levels]. 140 61

The authors describe the finding of Nocardia asteroides from a haemoculture in a patient with right-sided pneumonia and several predisposing factors (TB, chronic bronchitis, anamnestic hepatitis, chronic hepatopathy, anaemia, ethylism and a neoplasm revealed in the final stage). Early bacteriological diagnosis and aimed antimicrobial therapy led to radical improvement of the very dramatic clinical condition. The authors discuss the possible higher incidence of the infectious agent, which previously was detected only very rarely.
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PMID:[Isolation of Nocardia asteroides using hemoculture (clinical report)]. 146 81


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