Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we investigated the regulation of insulin-like growth factor II gene expression to explain a role for this growth factor in concert with hepatitis B virus involvement in the development of hepatocellular carcinoma from cirrhosis. Sections of normal liver and tumor and non-tumor-bearing liver disease tissue were hybridized in situ with [35S]-labeled insulin-like growth factor II oligonucleotide probe. Parallel sections were tested for presence of insulin-like growth factor II polypeptide using immunohistochemistry. To investigate a possible role for hepatitis B virus in insulin-like growth factor II gene expression in hepatocellular carcinoma, results were analyzed against patient seropositivity for hepatitis B virus. Levels of insulin-like growth factor II transcripts in normal liver (n = 4) sections and in those from non-tumor-bearing individuals (n = 10) were so low that specific signal was not detectable above homogeneous tissue background. In contrast, 4 of 8 (50%) of the sections of hepatocellular carcinoma arising from cirrhosis or noncirrhotic chronic liver disease with hepatitis B virus involvement showed increased expression of insulin-like growth factor II messenger RNA transcripts. Up-regulation was observed in cell foci in the hepatocellular regions of the surrounding cirrhotic lobular cells and the fibrous septa. Numerous cell foci were observed in patch distribution in the tumor areas. The level of insulin-like growth factor II messenger RNA transcripts in sections of hepatocellular carcinoma arising from cirrhotic and noncirrhotic tissues obtained from patients seronegative for hepatitis B virus was similar to that of normal liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of insulin-like growth factor II gene expression by hepatitis B virus in hepatocellular carcinoma. 184 51

The presence of pre-S polypeptides in paraffin wax embedded liver sections from the biopsy specimens of 15 hepatitis B surface antigen (HBsAg) seropositive patients (five with chronic persistent hepatitis (CPH), four with chronic active hepatitis (CAH), four with cirrhosis and two "healthy" HBsAg carriers) was investigated using monoclonal antibodies directed to distinct epitopes on pre-S1 (18/7 and TO 606) and pre-S2 (5535 and Q 19/10). Pre-S1 was found in 13 cases when MA 18/7 was used but in only one specimen when TO 606 was used. Pre-S2 was detected in all the biopsy specimens with 5535 and in eight samples with Q 19/10. Mild enzymatic digestion annulled the staining of all monoclonal antibodies but Q 19/10. No association was observed between pre-S polypeptide expression and hepatitis B virus (HBV) replication or disease severity. Pre-S polypeptides can be detected readily in paraffin wax embedded material but the results obtained largely depend on the monoclonal antibodies used.
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PMID:Detection of hepatitis B virus pre-S1 and pre-S2 determinants in paraffin wax embedded liver tissue: importance of reagents used. 185 86

Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5 patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80-120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations greater than 140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course.
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PMID:Plasma vasoactive intestinal polypeptide concentration determination in patients with diarrhea. 198 54

The changes of humoral substances in the blood of cirrhotic rats were studied together with their effects on portal hemodynamics at different stages during the development of cirrhosis. The profiles of humoral substances and hemodynamics in two different cirrhotic rat models were also investigated. During the development of cirrhosis, glucagon increased markedly in all stages, histamine and vasoactive intestinal polypeptide (VIP) increased in the early stage, serotonin (5-HT) and somatostatin (SS) increased in the middle and late stages. There were different patterns of humoral substances in different cirrhotic models. Glucagon was the main humoral substance elevated in CCL4 induced cirrhosis, but histamine and 5-HT were mainly elevated in the blood in thioacetamide (TAA) induced cirrhosis. The hemodynamics altered differently in different stages during the development of cirrhosis and differently in the two cirrhotic rat models. Exchange transfusions between normal and cirrhotic rats resulted in an elevation of portal flow in normal rats, but no such changes were found after exchange pressure and an increase of portal blood transfusions between normal rats. The relationship between the humoral substances and portal hemodynamics is discussed. The results of this study strongly support the hypothesis of "humoral mechanism" in the pathogenesis of portal hypertension due to cirrhosis.
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PMID:Changes of blood humoral substances in experimental cirrhosis and their effects on portal hemodynamics. 212 49

Homozygosity for alpha 1-antitrypsin deficiency, usually of the genotype PIZZ, is one of the more common single gene defects in infants of European origin, occurring in about 1 in 2000 to 1 in 7000 of the newborn population. About 17% of such infants present with neonatal hepatitis and a small number with intracranial haemorrhage thought to be caused by vitamin K deficiency associated with cholestasis. At least 3% of PIZZ infants will die of cirrhosis in later childhood unless successfully treated by liver transplant. The pathogenesis of the liver disease is not understood and this is unsatisfactory both for treatment and for genetic counselling. The locus coding for alpha 1-antitrypsin (alpha 1AT) is designated PI for proteinase inhibitor. Careful study of the genotypes at this locus in neonatal disease shows that the only certain association is with the homozygous PIZZ genotype. The mutation results in a normal rate of synthesis of a polypeptide that becomes entrapped in the endoplasmic reticulum of the hepatocyte. Some other factor (or factors), as yet unidentified, determines whether severe liver damage results. The low level of alpha 1AT in the plasma seems unlikely to be the primary cause of damage but may play a secondary role. There is some evidence that the other factor(s) may be familial since in one study, though not in all, a high correlation for severity of liver disease was found between PIZZ siblings. The heterogeneity of the clinical course does not result from heterogeneity of PIZ alleles and there is no evidence that it is determined by variation in other related genes on chromosome 14. Only two possible clues have emerged so far. There is some evidence of a protective effect of breast-feeding, and a recent study has found the HLA class II DR3 antigen to be more common than expected in children with alpha 1-antitrypsin deficiency and liver disease. Accumulation of alpha 1AT protein in the hepatocytes may predispose them to some unidentified alteration of the immune response. It is possible that lack of antiprotease activity in the plasma might exacerbate the original damage, so the possibility of useful therapy with alpha 1AT cannot be ruled out entirely. At present, there is no valid way of predicting the severity of disease in a PIZZ child; hence, it is common for parents of a severely affected child to wish to terminate any future PIZZ pregnancy. The most direct method to diagnose the PIZZ genotype of a chorion villus sample is by allele-specific hybridization or sequencing of amplified DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetics of alpha 1-antitrypsin deficiency in relation to neonatal liver disease. 218 61

Tissue Polypeptide Antigen (TPA) and alpha 1-fetoprotein (AFP) were determined in sera of 21 patients with hepatocellular carcinomas, in 20 patients with extrahepatic carcinomas and metastases of the liver, as well as in 26 patients with cirrhosis of the liver. TPA was increased (greater than 85 U/L) in all patients with malignant hepatomas, in 80% of patients with metastatic liver cancer and in 35% of patients with cirrhosis of the liver. The critical serum TPA level, above which only malignant liver tumours lay, was statistically evaluated and found to be 187 U/L. All patients with benign liver disease and half of the patients with metastatic liver disease showed TPA values lower than 187 U/L. All of the patients with hepatocellular carcinoma and half of the patients with metastatic liver cancer had TPA values greater than 187 U/L; all of our patients with cirrhosis of the liver, as well as half of the patients with metastatic liver cancer had lower TPA values. 86% out of all hepatoma patients showed increased AFP levels (greater than 9 ng/ml), whereby the AFP concentrations were in the range which is highly suggestive of hepatoma (greater than 174 ng/ml) in 67% of all patients with malignant hepatomas. Patients with metastatic liver cancer and cirrhosis of the liver had AFP levels lower than 174 ng/ml AFP. TPA is an unspecific tumour marker, which can be used together with AFP in the diagnosis of unclear defects in liver parenchyma, in supervision of cirrhosis, as well as in control assessment during chemotherapy or after tumour resection.
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PMID:[Serum concentrations of tissue polypeptide antigen and alpha 1-fetoprotein in patients with primary liver cancer, liver metastasis and liver cirrhosis]. 240 89

Tissue polypeptide antigen (TPA) is a polypeptide isolated from malignant cells and found in high concentration in the serum of patients with various tumors. No information is available with respect to hepatocellular carcinoma (HCC). Serum TPA concentrations were measured in 290 patients with HCC, 85 healthy controls, 33 patients with amebic hepatic abscesses, 43 with chronic hepatitis or cirrhosis, and 39 with acute hepatitis. Raised values were found in 96% of the HCC patients, but also in 61% of patients with amebic abscesses, 86% with chronic hepatic parenchymal disease, and 90% with acute hepatitis. If a cut-off level of 500 IU/L was used, this reduced the sensitivity of TPA in HCC to 46%, but still left 46% of patients with acute hepatitis with raised values. TPA is comparable in sensitivity with alpha-fetoprotein as a marker for HCC, but its lack of specificity severely limits its clinical usefulness.
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PMID:The value of serum concentrations of tissue polypeptide antigen in the diagnosis of hepatocellular carcinoma. 242 21

This study was undertaken in order to compare the usefulness of three indices of tumour proliferation in detecting primary hepatocellular carcinoma (HCC) and in differentiating this neoplasm from liver cirrhosis. In 10 patients with HCC and in 63 with liver cirrhosis serum alpha-fetoprotein (AFP), tissue polypeptide antigen (TPA) and ferritin were assayed. Increased levels of AFP but not of TPA and ferritin were observed in HCC as compared to liver/cirrhosis. The receiver-operating characteristic curves demonstrated that AFP is more discriminating between HCC and liver cirrhosis than the other two markers. Correlations between liver function tests and serum markers were observed in liver cirrhosis but no in HCC. We can conclude that AFP is more useful than TPA and ferritin in detecting HCC in patients with liver cirrhosis, owing to the high frequency of false positive results of the latter two indices in liver cirrhosis. Liver dysfunction is probably involved in increasing all these markers of malignancy, thus reducing the specificity of these tests.
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PMID:Alpha-fetoprotein, tissue polypeptide antigen and ferritin in diagnosing primary hepatocellular carcinoma in patients with liver cirrhosis. 247 90

This study was undertaken in order to compare the ability of 4 tumour markers to discriminate between liver cirrhosis patients with or without hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA 19-9 and tissue polypeptide antigen (TPA) were determined in 63 patients with liver cirrhosis and in 25 patients with HCC in liver cirrhosis. All 4 serum markers were found to be increased in a number of liver cirrhosis patients, regardless of the presence of HCC. AFP was found to be more elevated in HCC patients as compared to the other group; no difference was observed for CA 19-9, CEA and TPA. A significant correlation was detected in HCC patients between AFP and TPA. Significant correlation were detected in all except HCC patients between liver function tests and TPA. We can conclude that AFP determination remains as yet the only suitable marker able to detect HCC in liver cirrhosis. The newly introduced serum marker CA 19-9 is, as previously reported, unhelpful for CEA. TPA can in some instances (i.e. in the absence of an important hepatic cell necrosis or cholestasis) provide a clue to neoplastic growth.
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PMID:Do CA 19-9 and TPA play a minor role as compared to AFP in diagnosing primary hepatocellular carcinoma? 247 97

In order to evaluate the behaviour of alpha-fetoprotein (AFP) and Tissue Polypeptide Antigen (TPA) in non neoplastic chronic hepatic diseases 60 patients suffering from chronic hepatitis have been studied, 28 of them with different ethiology cirrhosis, 4 with primary biliary cirrhosis (CBP), 18 with chronic active hepatitis (ECA), 5 with chronic persistent hepatitis (ECP), 3 suffering from alcoholic and 2 drug-induced hepatitis. In each case the diagnosis was biopsy-proved. We have found that TPA clearly shows an increase in about 90% of cirrhosis and in about 50% of ECA. Moreover, the group with non-A, non-B (NANB) cirrhosis and chronic hepatitis has shown a statistically significant correlation between TPA and alanine aminotransferase (ALT). On the other hand, AFP hants' shown statistically significant variations. The reasons of the TPA increase must probably be looked for in the marked sensitivity of this protein to non neoplastic tissues in rapid regeneration, in addition to the sensitivity to neoplastic tissues. Further studies will be carried out to evaluate the usefulness of TPA to tracing possible cytolitic relapses or any resumption of activity in hepatic cirrhosis.
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PMID:Alpha-fetoprotein and tissue polypeptide antigen in non neoplastic hepatic disorders. 248 Apr 32


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