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)

Since 1983 large number of people are being encountered with arsenic toxicity due to drinking of arsenic contaminated water (0.05-3.2 mg/l) in 6 districts of West Bengal. Clinical and various laboratory investigations were carried out on 156 patients to ascertain the nature and degree of morbidity and mortality that occurred due to chronic arsenic toxicity. All the patients studied had typical rain drop like skin pigmentation (being inclusion criteria) while thickening of palm and sole were found in 65.5% patients. Other features included weakness (70%), gastro-intestinal symptoms (58.6%), involvement of respiratory system (57.08%) and nervous system (50.6%). Lung function tests showed restrictive lung disease in 53% (9/17) and combined obstructive and restrictive lung disease in 41% (7/17) of patients. Abnormal electromyography was found in 34.8% (10/29) and altered nerve conduction velocity in 34.8% (10/29) of cases. Enlargement of liver was found in 120 cases (76.9%) while splenomegaly in 31.4% cases. Liver function test showed elevated globulin level in 15.8% and alkaline phosphatase in 51.3%, alanine amino transferase (ALT) in 11.8% and aspartate amino transferase (AST) in 27.6% of cases. Evidence of portal hypertension was found in 33.3% patients. Liver biopsy reports of 45 patients showed non-cirrhotic portal fibrosis in 41, cirrhosis in 2 and normal histology in 2 cases. There was no correlation between the quantity of arsenic taken through water and the level of arsenic in hair, nail, liver tissues and the degree of fibrosis. There were 5 deaths of which one had skin cancer. The various non-cancer manifestations which were observed in these patients were much severe than those reported in similar cases in other parts of the world.
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PMID:Chronic arsenic toxicity in west Bengal--the worst calamity in the world. 960 Nov 81

Hepatitis C virus (HCV) infection is a major health problem that leads to cirrhosis and hepatocellular carcinoma in a substantial number of infected individuals, estimated to be 100-200 million worldwide. Unfortunately, immunotherapy or other effective treatments for HCV infection are not yet available, and interferon administration has limited efficacy. Different approaches to HCV therapy are being explored, and these include inhibition of the viral proteinase, helicase, and RNA-dependent RNA polymerase and development of a vaccine. Here we present the design of selective inhibitors with nanomolar potencies of HCV NS3 proteinase based on eglin c. These eglin c mutants were generated by reshaping the inhibitor active site-binding loop, and the results emphasize the role played by residues P5-P4' in enzyme recognition. In addition, alanine scanning experiments provide evidence that the N terminus of eglin c also contributes to NS3 binding. These eglin inhibitors offer a unique tool for accurately assessing the requirements for effective inhibition of the enzymatic activity of NS3 and at the same time can be considered lead compounds for the identification of other NS3 inhibitors in targeted design efforts.
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PMID:Design of selective eglin inhibitors of HCV NS3 proteinase. 970 81

A 63-year-old woman who had received hemodialysis therapy since she fell acute on chronic renal failure 4 years ago presented with multiple joint pain. Nephrocalcinosis was not detected by abdominal X-ray when hemodialysis therapy was initiated. Laboratory testing showed azotemia, anemia, hypoproteinemia and mild liver dysfunction but no liver cirrhosis. Biopsied bone tissue demonstrated numerous calcium oxalate crystal depositions. Laparoscopy revealed black liver in macroscopic view. Histological studies showed numerous lipofuscin-like dark brown granules were deposited in hepatocytes. The activity of alanine : glyoxylate aminotransferase (AGT) was less than 0.1 U/g in biopsied patient's liver tissue. Generally, clinical symptoms demonstrated by Japanese primary hyperoxaluria type I (PH-I) patients are milder than those of European patients. Some PH-I patients may successfully avoid urinary tract calcification unless they fall into oliguria by some other causes. The lipofuscin granules are most likely the source of the dark color. Massive deposition of the lipofuscin granules indicated that the duration of the liver metabolic abnormality had lasted for long time. Thus, black liver may be related to a mild form of PH-I.
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PMID:A case of late onset primary hyperoxaluria type I (PH-I) presented with black liver. 977 23

In this study, we evaluated the correlation between alanine aminotrasferase levels and hepatitis C virus genotypes in liver transplant patients. We studied 18 patients who had undergone orthotopic liver transplantation because of end-stage cirrhosis (n = 9) or hepatocellular carcinoma (n = 9) hepatitis C virus related. Serum HCV-RNA testing was performed monthly on all the 18 series of serum samples from the first week after liver transplant until the end of the follow up, this period ranging from 1 to 39 months. After liver transplantation, serum HCV-RNA was detected in 14 patients (78%). Of the 8 patients infected with subtype 1b. 1 remained asymptomatic, 2 developed acute liver failure and 5 developed chronic hepatitis. In patients infected with types 1a (Choo et al., 1989), 2a (Choo et al., 1989), with a mixed infection 1b/3 (Kuo et al., 1989) or with an undetermined genotype, significant laboratory abnormalities were not observed. Recurrence of hepatitis C virus infection after liver transplantation is common, and recurrent hepatitis occurs in 50% of cases. Genotype 1b appears to be associated with a higher rate of recurrent hepatitis, compared to other genotypes.
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PMID:Recurrence of hepatitis C virus infection after orthotopic liver transplantation: role of genotypes. 1019 Jan 12

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.
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PMID:Postoperative hepatic catabolic stress response in patients with cirrhosis and chronic hepatitis. 1065 74

Dipeptidyl peptidase (DPP) IV has roles in T-cell costimulation, chemokine biology, type-II diabetes and tumor biology. Fibroblast activation protein (FAP) has been implicated in tumor growth and cirrhosis. Here we describe DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP. Northern-blot hybridization showed that the tissue expression of DPP8 mRNA is ubiquitous, similar to that of DPPIV. The DPP8 gene was localized to chromosome 15q22, distinct from a closely related gene at 19p13.3 which we named DPP9. The full-length DPP8 cDNA codes for an 882-amino-acid protein that has about 27% identity and 51% similarity to DPPIV and FAP, but no transmembrane domain and no N-linked or O-linked glycosylation. Western blots and confocal microscopy of transfected COS-7 cells showed DPP8 to be a 100-kDa monomeric protein expressed in the cytoplasm. Purified recombinant DPP8 hydrolyzed the DPPIV substrates Ala-Pro, Arg-Pro and Gly-Pro. Thus recombinant DPP8 shares a postproline dipeptidyl aminopeptidase activity with DPPIV and FAP. DPP8 enzyme activity had a neutral pH optimum consistent with it being nonlysosomal. The similarities between DPP8 and DPPIV in tissue expression pattern and substrates suggests a potential role for DPP8 in T-cell activation and immune function.
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PMID:Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. 1101 66

The cause of muscle wasting and decreased plasma levels of branched chain amino acids (BCAA), valine, leucine, and isoleucine in liver cirrhosis is obscure. Here we have evaluated the effect of hyperammonemia. Rats were infused with either an ammonium acetate/bicarbonate mixture, a sodium acetate/bicarbonate mixture, or saline for 320 minutes. The parameters of leucine and protein metabolism were evaluated in the whole body and in several tissues using a primed constant intravenous infusion of L-[1-14C]leucine. Ammonium infusion caused an increase in ammonia and glutamine levels in plasma, a decrease in BCAA and alanine in plasma and skeletal muscle, a significant decrease in whole-body proteolysis and protein synthesis, and an increase in leucine oxidized fraction. A significant decrease in protein synthesis after ammonium infusion was observed in skeletal muscle while a nonsignificant effect was observed in liver, gut, heart, spleen, and kidneys. We conclude that the decrease in plasma BCAA after ammonia infusion is associated with decreased proteolysis and increased leucine oxidized fraction.
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PMID:Effect of hyperammonemia on leucine and protein metabolism in rats. 1107 24

We have utilized [(15)N]alanine or (15)NH(3) as metabolic tracers in order to identify sources of nitrogen for hepatic ureagenesis in a liver perfusion system. Studies were done in the presence and absence of physiologic concentrations of portal venous ammonia in order to test the hypothesis that, when the NH(4)(+):aspartate ratio is >1, increased hepatic proteolysis provides cytoplasmic aspartate in order to support ureagenesis. When 1 mm [(15)N]alanine was the sole nitrogen source, the amino group was incorporated into both nitrogens of urea and both nitrogens of glutamine. However, when studies were done with 1 mm alanine and 0.3 mm NH(4)Cl, alanine failed to provide aspartate at a rate that would have detoxified all administered ammonia. Under these circumstances, the presence of ammonia at a physiologic concentration stimulated hepatic proteolysis. In perfusions with alanine alone, approximately 400 nmol of nitrogen/min/g liver was needed to satisfy the balance between nitrogen intake and nitrogen output. When the model included alanine and NH(4)Cl, 1000 nmol of nitrogen/min/g liver were formed from an intra-hepatic source, presumably proteolysis. In this manner, the internal pool provided the cytoplasmic aspartate that allowed the liver to dispose of mitochondrial carbamyl phosphate that was rapidly produced from external ammonia. This information may be relevant to those clinical situations (renal failure, cirrhosis, starvation, low protein diet, and malignancy) when portal venous NH(4)(+) greatly exceeds the concentration of aspartate. Under these circumstances, the liver must summon internal pools of protein in order to accommodate the ammonia burden.
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PMID:Alanine metabolism in the perfused rat liver. Studies with (15)N. 1142 41

Abnormal liver function in thyroid disorders may be secondary to thyrotoxicosis or to autoimmune injury to the liver. We report the case of a 36-year-old female who developed jaundice and pruritus with mild cholestasis and moderately elevated transaminase levels. The diagnosis of Graves' disease was made shortly thereafter. Laboratory findings were: alanine and aspartate aminotransferase 219 (IU/I (N: 9-50) and 102 IU/I (N: 10-15) respectively, alkaline phosphatase 336 IU/I (N: 40-135), bilirubin 24 micromol/I (N: 2-23), and gamma-glutamyl transpeptidase 232 IU/I (N: 9-43). Abdominal ultrasonography showed normal bile ducts; echocardiography ruled out heart failure; viral and autoimmune markers for hepatitis and cirrhosis were negative. Percutaneous liver biopsy showed moderate intrahepatic steatosis, anisokaryosis, lymphocyte infiltration in the portal areas, and Kupffer cell hyperplasia. Outcome was favorable after seven months of iodine therapy, confirming the diagnosis of thyrotoxicosis hepatitis.
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PMID:[Thyrotoxicosis hepatitis: a case report]. 1145 76

Exposure to nitrosamines may be the occupational risk factor for liver cirrhosis. 2-(Allylthio)pyrazine, a chemopreventive agent, inhibits CYP2E1 and induces phase II enzymes. We examined the effects of 2-(allylthio)pyrazine on hepatic fibrosis, a prepathologic state of cirrhosis, and on the expression of transforming growth factor-beta1 induced by dimethylnitrosamine. Treatment of rats with dimethylnitrosamine for 4 weeks increased plasma alanine/aspartate amino-transferase and y-glutamyl transpeptidase activities, and bilirubin content, whereas the total plasma protein and albumin levels were decreased. 2-(Allylthio)pyrazine inhibited dimethylnitrosamine-induced increases in the enzyme activities and bilirubin, and restored the plasma protein and albumin contents. Masson's trichrome staining showed that dimethylnitrosamine induced liver fibrosis, the extent of which was reduced by 2-(allylthio)pyrazine treatments. Reverse transcription-polymerase chain reaction analysis revealed that 2-(allylthio)pyrazine inhibited production of transforming growth factor-beta1 mRNA by dimethylnitrosamine. These results demonstrated that 2-(allylthio)pyrazine might inhibit dimethylnitrosamine-induced liver fibrosis due to suppression of CYP2E1 expression and transforming growth factor-beta1 production.
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PMID:2-(Allylthio)pyrazine, a cancer chemopreventive agent, inhibits liver fibrosis induced by dimethylnitrosamine in rats: role of inhibition of transforming growth factor-beta1 expression. 1148 6


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