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)

The authors investigated dynamic changes and the interaction of the plasma renin activity (PRA), plasma aldosterone (PAC), i.e. the main representatives of sodium retaining systems, and of the atrial natriuretic factor (ANF) the decisive natriuretic substance in acute expansion of the extracellular volume (ECV) by infusion of two litres of saline in six controls, seven patients with essential hypertension and liver cirrhosis without ascites (6 patients) and with ascites (6 patients). The expansion evoked controversial changes of these systems. It led to a rise of ANF and suppression of PAC and PRA. Although ANF rose after infusion to the roughly similar range (12.4 to 15.7 pmol/l), the natriuretic response to expansion differed significantly in different groups of patients. It was most marked in hypertonic subjects (517.2 to 93.2 mumols/min) and practically zero in ascitic liver cirrhosis (54.2 +/- 44.2 mumols/min). The explanation of this finding may be the persistence of high activity of the renin-angiotensin-aldosterone system despite its partial inhibition by infusion of saline in cirrhosis of the liver (PRA 1.69 +/- 0.66 nmols/l/hr., PAC 1.12 nmol/l). For the renal response to acute expansion of the ECV thus not only the absolute plasma concentration of ANF is decisive but also its ratio to the activity of the sodium retaining renin-angiotensin-aldosterone system.
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PMID:[Mutual interaction of the renin-angiotensin system and the atrial natriuretic factor in the renal response to acute volume loading]. 214 4

We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes.
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PMID:The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes. 840 27

A 26-year-old woman, after cesarean section in the 33rd week of gestation, developed after delivery thrombosis of the popliteal vein, pulmonary embolism and thrombosis of the portal vein. After completion of a six month period of oral anticoagulation, laboratory investigations revealed diminished levels of plasminogen and free protein S antigen as well as APC-resistance due to heterozygous FV R506Q mutation. After six uneventful years, abdominal sonography and magnetic resonance examination, performed because of abdominal pain, showed liver cirrhosis with Budd-Chiari syndrome. Additional hematological investigations led to the diagnosis of polycythemia vera. Association of myeloproliferative disorders, mainly polycythemia vera, with splanchnic venous thrombosis is well known and should always be looked for.
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PMID:[A 26-year-old woman with splanchnic vein thrombosis as the initial manifestation of polycythemia vera]. 1051 20

Renal Na+ handling abnormalities have been shown in preascitic cirrhosis. To investigate the underlying pathophysiology, the effects of different sodium intakes on Na(+) balance and renal hemodynamics were assessed at 100 mEq Na+/day (low-sodium diet [LSD]) and after 6 days of 250 mEq Na+/day (high-sodium diet [HSD]). Eight asymptomatic patients with cirrhosis (Pugh-Child A class) (PAC) and 10 healthy controls (CON) were studied. At HSD, although CON readjusted Na+ excretion within the fourth day, PAC did not reach the new balance and developed a final greater Na+ retention (+437 mEq in PAC v +228 mEq in CON, P<.001). In PAC, fractional Na+ excretion (FENa) was significantly lower than in CON at LSD (P<.05), and, after HSD, increased in both groups (P<.05). In PAC, renal vascular resistances (RVR) at LSD resulted lower than in CON (P<.05) and failed to decrease after HSD. As a consequence, after HSD, glomerular filtration rate and renal plasma flow failed to increase in PAC. PRA and plasma aldosterone were significantly lower in PAC, than in CON at LSD (P<.05), and decreased in both groups after HSD (P<.05). Proximal Na+ reabsorption (RProx) [as indicated by fractional free water clearance measured in a state of maximal water diuresis] at LSD was lower in PAC than in CON (P<.05) and decreased in both groups after HSD (P<.05). In summary, early stages of cirrhosis are characterized by: (1) a reduction of RVR, probably associated with splanchnic vasodilation; (2) a Na+ retention already at LSD, as indicated by the lower FENa observed in PAC, that produces extracellular volume (ECV) expansion, with a consequent RProx and renin-angiotensin-aldosterone axis (RAS) suppression; (3) a greater Na+ retention after HSD, associated with an abnormal adaptation of renal hemodynamic, a greater ECV expansion and a consequent Rprox and RAS suppression. These data show the presence of early renal hemodynamic dysfunction in PAC. Our findings also show in this phase of the disease a preserved adaptation of RProx and RAS, thus suggesting that the observed tubular Na+ reabsorption derangement is probably related to abnormal ANP behavior.
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PMID:Sodium retention in preascitic stage of cirrhosis. 1132 May 1

To assess whether an increased production of nitric oxide is involved in the circulatory and renal alterations of cirrhosis, we evaluated systemic hemodynamics (echocardiography), renal hemodynamics, and sodium handling (lithium clearance method), plasma renin activity (PRA), aldosterone (PAC), and norepinephrine in 7 patients (3 men, mean age 65 +/- 2 years) with compensated cirrhosis, portal hypertension, and hyperdynamic circulation during intravenous N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg bolus plus 0.05 mg/kg. min for 120 minutes) or placebo (the vehicle) in a randomized, placebo-controlled, crossover study. Administration of L-NMMA resulted in significant reductions in plasma and urinary nitrite levels and plasma cyclic guanosine monophosphate (cGMP), indicating effective inhibition of nitric oxide synthase. L-NMMA also significantly reduced cardiac index (-13%) and increased systemic vascular resistance (+26%), arterial pressure (+9%), renal blood flow (+12%), glomerular filtration rate (+12%), and sodium excretion (+25%). Changes in sodium excretion were caused by both enhanced filtered sodium load and reduced sodium reabsorption in the proximal tubule. Plasma norepinephrine significantly decreased in response to L-NMMA, and there was a trend for reductions in PRA and PAC. Placebo had no appreciable effect on any of the measured parameters. These results indicate that in patients with compensated cirrhosis, portal hypertension and hyperdynamic circulation inhibition of nitric oxide synthase corrects the altered systemic hemodynamics and improves renal function and sodium excretion.
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PMID:Hemodynamic, renal, and endocrine effects of acute inhibition of nitric oxide synthase in compensated cirrhosis. 1143 29

In patients with cirrhosis and portal hypertension, standing induces a reduction in cardiac index (CI) and an increase in systemic vascular resistance index. Our previous studies indicate that this abnormal hemodynamic response to standing is due to an altered myocardial function, because cirrhotic patients are unable to compensate for the reduced preload with an increase in left ventricular (LV) ejection fraction (EF) and stroke volume. To evaluate whether the cardiac dysfunction in cirrhosis is influenced by canrenone, an aldosterone antagonist, 8 patients with preascitic, nonalcoholic cirrhosis, and portal hypertension underwent echocardiographic assessment of LV function and systemic hemodynamics and determinations of plasma volume, urinary sodium excretion, and plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (PNE) when on a 150-mmol/d-sodium diet (baseline), after 1 month on canrenone (100 mg/d) plus a 40-mmol/d-sodium diet and after 1 month on canrenone plus a 150-mmol/d-sodium diet. Echocardiographic evaluation was performed with the patient in the supine position and during active standing. At baseline, patients had high plasma volume and normal renal function, PRA, PAC, and PNE. CI, LVEF, and stroke volume index were also normal. Standing caused a significant reduction in CI and LVEF. After canrenone and either sodium diet, CI significantly decreased, and PRA and PNE increased in the supine position. On standing, LVEF and CI did not decrease further. Plasma volume significantly decreased only after low-sodium diet plus canrenone. In conclusion, canrenone normalizes the cardiac response to the postural challenge in patients with preascitic cirrhosis.
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PMID:Cardiovascular effects of canrenone in patients with preascitic cirrhosis. 1261 26

Major etiologic factors associated with human hepatocellular carcinomas (HCCs) include infection with hepatitis C (HCV) and hepatitis B virus (HBV), excess alcohol intake and aflatoxin B(1) exposure. While the G-->T p53 mutation at codon 249 has been identified as a genetic hallmark of HCC caused by aflatoxin B(1), the genetic profile associated with other etiologic factors appears to be less distinctive. In our study, we screened HCCs resulting from HCV infection (51 cases), HBV infection (26 cases) or excess alcohol intake (23 cases) for alterations in genes involved in the RB1 pathway (p16(INK4a), p15(INK4b), RB1, CDK4 and cyclin D1), the p53 pathway (p53, p14(ARF) and MDM2) and the Wnt pathway (beta-catenin, APC). Alterations of the RB1 pathway, mainly p16(INK4a) methylation, loss of RB1 expression and cyclin D1 amplification, were most common (69-100% of cases). There was a significant correlation between loss of RB1 expression and RB1 methylation. All 24 HCCs with RB1 promoter methylation lacked RB1 expression, while none of the 67 cases with RB1 expression exhibited RB1 methylation (p < 0.0001), suggesting that promoter methylation is a major mechanism of loss of RB1 expression in HCCs. Alterations of the p53 pathway consisted mostly of p53 mutations or p14(ARF) promoter methylation (20-48%). Mutations of the p53 gene were found at a similar frequency (13-15%) in all etiologic groups, without any consistent base change or hot spot. Mutations of beta-catenin were found in 13-31% of cases, while no APC mutations were detected in any of the HCCs analyzed. With the exception of only 3 of 39 cases (8%), cyclin D1 amplification and beta-catenin mutations were mutually exclusive, supporting the view that cyclin D1 is a target of the Wnt signaling pathway. Overall, the RB1, p53 and Wnt pathways were commonly affected in HCCs of different etiology, probably reflecting common pathogenetic mechanisms, i.e., chronic liver injury and cirrhosis, but tumors associated with alcoholism had more frequent alterations in the RB1 and p53 pathways than those caused by HCV infection.
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PMID:Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis. 1284 70

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies, but the molecular mechanisms of hepatocarcinogenesis remain unclear. Although p53 mutations are frequently observed in Asian HCC, it is not a common event in Western HCC. Recent studies suggest that tumor suppressor genes (TSGs) can also be silenced through epigenetic disruption, such as promoter CpG island methylation, during carcinogenesis. To further understand the molecular mechanism of hepatocarcinogenesis, we have investigated the promoter methylation status of nine TSGs (SOCS-1, GSTP, APC, E-cadherin, RAR-beta, p14, p15, p16, and p73) in 51 cases of HCC using methylation-specific polymerase chain reaction. We found that 82% of HCCs had methylation of at least one TSG promoter. The most frequently methylated TSGs in HCC were: SOCS-1 (65%), GSTP (54%), APC (53%), E-cadherin (49%), and p15 (49%). Methylation of SOCS-1, GSTP, APC, E-cadherin, and p15 was more frequent in HCC than in nontumor liver (P < 0.05). Methylation of SOCS-1, GSTP, and p15 was also significantly more frequent in HCC than cirrhotic liver (P < 0.05). Although methylation of one or two genes could be seen in both nontumor and cirrhotic livers, 53% of the HCC cases had three or more TSG promoters methylated, in comparison to 0% in nontumor liver and 13% in cirrhosis (P = 0.001). Methylation of SOCS-1, APC, and p15 was more frequently seen in hepatitis C virus-positive HCC than hepatitis C virus/hepatitis B virus-negative HCC. Our data suggest that promoter hypermethylation of TSGs is a common event in HCC and may play an important role in hepatocarcinogenesis.
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PMID:Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. 1293 51

To determine the methylation profile of multiple tumor-related genes during multistep hepatocarcinogenesis, we investigated the methylation status of CpG islands of 9 genes, using methylation-specific polymerase chain reaction for 60 paired hepatocellular carcinoma (HCC) and non-HCC liver tissue samples, 22 dysplastic nodule (DN), 30 liver cirrhosis (LC), 34 chronic hepatitis (CH) and 20 normal liver samples. The methylation status of 9 genes was correlated to the clinicopathological findings of HCC patients. All HCC samples showed methylation of at least one gene, whereas it was shown in 72.7% of DN and 40% of LC, but was not shown in CH and normal liver samples (P < 0.001). The number of genes methylated showed a stepwise increase with the progression of stages (0 for normal liver and CH, 0.5 for LC, 1.5 for DN, and 3.7 for HCC (P < 0.001)). The genes frequently methylated in HCC were APC (81.7%), GSTP1 (76.7%), RASSF1A (66.7%), p16 (48.3%), COX-2 (35%), and E-cadherin (33.3%). COX-2, p16, RASSF1A, and TIMP-3 were not methylated in LC and CH from patients without concurrent HCC. Chronic liver diseases with concurrent HCC showed higher methylation frequencies of the tested genes, and a higher number of methylated genes than those without concurrent HCC. HCC patients with methylation of E-cadherin or GSTP1 showed poorer survival than those without (P = 0.034 and 0.043, respectively). In conclusion, our results indicated that CpG island methylation of tumor-related genes is an early and frequent event, and accumulates step-by-step during a multistep hepatocarcinogenesis. CpG island methylation of E-cadherin or GSTP1 might serve as a potential biomarker for prognostication of HCC patients.
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PMID:Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis. 1450 45

Portal vein thrombosis is one of the main prehepatic causes of portal hypertension. The most frequent causes of thrombosis in this localization, apart from hepatic cirrhosis, are the following: acute inflammatory diseases and abdominal cancers, traumas, proliferative diseases of the hematopoietic system. In recent years attention was given to disorders in hemostasis, such as thrombophilia, in the course of which thrombosis development is particularly common. The authors present 10 patients after an incident of portal vein thrombosis, in which primary hepatic pathology was excluded and tests directed at thrombophilia were performed. In seven patients abnormalities in the examined parameters were found, and what is more, in two cases they had a complex character and involved more than one parameter. In five patients hyperhomocysteinemia was found. Among them, in two patients there was also a decreased protein S activity and in one of them there was also APC-resistance. In the next two patients there were abnormalities in one of the examined parameters - APC-resistance. Hyperhomocysteinemia was found in all patients with idiopathic thrombosis, and in one of them there were concurrent changes in protein S activity and APC-resistance. In patients with the history of portal vein thrombosis diagnostics of thrombophilia should be performed.
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PMID:[Portal vein thrombosis in patients with thrombophilia--own observations]. 1620 49


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