Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C) in liver biopsies from adults (n=19) with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex) technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05). At the level of electron microscopy, protein localization in endoplasmic reticulum (ER) membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT), serum level of HCV RNA or alpha-fetoprotein (AFP) on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging, proliferative activity of hepatocytes and serum AFP level represent more valuable indices of the disease progress than those provided by cellular expression of three potentially oncogenic HCV proteins in vivo.
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PMID:Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C) in chronic, long lasting hepatitis C virus (HCV) infection. 1816 75

The clinical significance of elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C virus (HCV) infection is not well defined. We analysed data from a population-based cohort of patients with HCV infection to assess the prevalence of elevated serum AFP, to determine its association with clinical and virologic parameters and with clinical outcomes. We defined a slightly elevated serum AFP level as 8 to <15 and a high-AFP level as > or =15 microg/L. Among 541 HCV-RNA-positive persons, 61 (11%) had a slightly elevated or high AFP at the time of consent. AFP > or =8 microg/L was associated with the older age, aspartate aminotransferase/alanine aminotransferase ratio >1, and higher alkaline phosphatase levels, but not with heavy alcohol use, IV drug use, genotype, viral load or duration of HCV infection. Among 192 persons with an AFP at liver biopsy, 17% had an AFP > or =8 microg/L. The sensitivity/specificity of an AFP level > or =8 in detecting Ishak 3-6 fibrosis was 39%/95%. Among 372 persons with a minimum of four AFP measurements over 6 years, 5% had persistently elevated AFP >8 microg/L, 19% had both elevated and normal AFP measurements, and 76% had persistently normal AFP. Elevated AFP at consent was associated with hepatocellular carcinoma (HCC) and end-stage liver disease. Over 6 years of follow-up, persistently elevated AFP was associated with the development of HCC; no person with AFP persistently <8 microg/mL developed HCC. Serial AFP measurements appear to be useful in identifying persons with advanced fibrosis and help to determine who needs periodic screening with liver ultrasound to detect HCC.
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PMID:Clinical significance of elevated alpha-fetoprotein in Alaskan Native patients with chronic hepatitis C. 1823 91

To compare the effects of alpha-ketoglutarate (alpha-KG) and melatonin on 24-h rhythmicity of oxidative stress in N-nitrosodiethylamine (NDEA)-injected Wistar male rats, melatonin (5 mg/kg i.p.) or alpha-KG (2 g/kg through an intragastric tube) was given daily for 20 weeks. In blood collected at 6 time points during a 24-h period, serum activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein (alpha-FP) were measured as markers of liver function. To assess lipid peroxidation and the antioxidant status, plasma levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured, together with the activity of erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST). NDEA augmented mesor and amplitude of rhythms in AST and ALT activity and plasma alpha-FP levels and mesor values of plasma TBARS, while decreasing mesor values of plasma GSH and erythrocyte SOD, CAT, GPx and GST. Acrophases were delayed by NDEA in all cases except for alpha-FP rhythm, which became phase-advanced. Co-administration of melatonin or alpha-KG partially counteracted the effects of NDEA. Melatonin decreased mesor of plasma TBARS and augmented mesor of SOD activity. The results indicate that melatonin and alpha-KG are effective in protecting from NDEA-induced perturbation of 24-h rhythms in oxidative stress. Melatonin augmented antioxidant defense in rats.
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PMID:24-hour rhythms in oxidative stress during hepatocarcinogenesis in rats: effect of melatonin or alpha-ketoglutarate. 1833 50

The prevalences of chronic infection by hepatitis C virus (HCV) and its genotypes vary among countries and ethnic groups. Among patients with end-stage renal disease (ESRD) and transplant recipients, the evolution of hepatic disease seems atypical and has not been established. In this study we compared the prevalence and HCV genotypic distribution among Brazilian patients with ESRD on dialysis or with transplantations. Moreover, we sought to compare the behavior of biochemical markers of hepatic activity of HCV infection in both groups. We prospectively evaluated 87 ESRD patients on dialysis and 105 transplant patients. Blood samples were obtained to perform qualitative HCV-RNA, genotyping, and, periodically, serum levels of aminotransferases (ALT, AST), gamma-glutamyltransferase (GGT), alpha-fetoprotein (AFT), and albumin. The prevalence of HCV in ESRD patients was similar to recipients (19.5% vs 25.7%; P = NS) and the most frequent genotype was 1a. There was no difference in the mean values of ALT, GGT, AFT, and serum albumin between both groups with HCV infection. The mean values of aminotransferases were slightly elevated and a high frequency of patients evolved with persistently normal parameters. In contrast, the mean values of the GGT were 3 or 4 times above the reference limit and a greater frequency of patients evolved with values persistently elevated in the 2 groups. In conclusion, in the 2 groups the prevalence of HCV infection was elevated; the most frequent genotype was 1a. Among the biochemical parameters, GGT seemed to be useful as an indirect marker of liver disease.
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PMID:Gamma-glutamyltransferase activity in chronic dialysis patients and renal transplant recipients with hepatitis C virus infection. 1858 96

Spontaneous intrahepatic bleeding is a rare condition. In the absence of trauma, intrahepatic hematoma may be due to underlying liver disease. We report a case of hepatocellular carcinoma in the patient who had huge intrahepatic hematoma without definite intrahepatic tumor at the time of initial presentation. A 54-year-old man was admitted to our hospital with a sudden onset of upper abdominal pain. Initial abdominal CT scan showed huge hematoma measuring more than 13 cm in diameter in the right lobe of the liver. However, there was no enhancing lesion in the liver. Laboratory data showed high alanine aminotransferase, alpha-fetoprotein and positive HBsAg. The MRI and angiography could not also depict any mass in the liver. The patient was treated with percutaneous drainage on the intrahepatic hematoma. The cytology from drainaged blood revealed no malignant cell. After hematoma decreased, follow-up CT scan depicted an enhancing tumor in the liver. He underwent right hepatic lobectomy and histopathological examination showed hepatocellular carcinoma.
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PMID:[A case of hepatocellular carcinoma presented as a huge intrahepatic hematoma]. 1860 42

One of the focuses in current cancer chemoprevention studies is the search for nontoxic chemopreventive agents that inhibit the initiation of malignant transformation. Cancer biomarkers are quantifiable molecules involved in the physiologic or pathologic events occurring between exposure to carcinogens and the development, progression of cancer. Biomarkers may be the consequence of a continuous process, such as increased cell mass, or a discrete event, such as genetic mutation. Analysis of tumor markers can be used as an indicator of tumor response to therapy. Gallic acid is a naturally available polyphenol, possess strong antioxidant activity with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated the antiproliferative effect of gallic acid during diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in male wistar albino rats. DEN treatment resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, acid phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, 5'-nucleotidase, bilirubin, alpha-fetoprotein, carcinoembryonic antigen, argyophillic nucleolar organizing regions, and proliferating cell nuclear antigen. Gallic acid treatment significantly attenuated these alterations and decreased the levels of AgNORs and PCNA. These finding suggests that gallic acid is a potent antiproliferative agent against DEN-induced HCC.
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PMID:Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat hepatocellular carcinoma. 1862 14

The aim of this case control study was to investigate the clinical significance of hepatitis B virus nuclear core antigen (HBcAg) in young cirrhotic patients. Fifteen cirrhotic patients with nuclear HBcAg in the liver biopsies were included. Their clinicopathological parameters as well as the core gene sequences were compared with those of a sex- and age-matched (1 to 2) control group. The mean follow-up periods were 124 +/- 80 and 102 +/- 43 months, respectively. Expression of nuclear HBcAg in cirrhotic liver was significantly associated with higher aspartate aminotransferase levels (P = 0.001), alanine aminotransferase levels (P < 0.001), and alpha-fetoprotein levels (P = 0.002), as well as a shorter duration to develop hepatocellular carcinoma or liver decompensation (Kaplan-Meier method, P = 0.044). Sequence analysis revealed mutations on the nuclear localization signal (NLS) of core protein in five cirrhotic patients with nuclear HBcAg (Q171K in four and Q179K in one patients). Site-directed mutagenesis experiments demonstrated that both the Q171K and Q179K mutation enhanced nuclear localization of the core protein. In conclusion, expression of nuclear HBcAg in young cirrhotic patients was associated with more severe hepatitis activities as well as an unfavourable long-term outcome. Mutations on the NLS of core protein were selected in some patients with nuclear HBcAg.
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PMID:Expression of hepatitis B virus nuclear core antigen in young cirrhotic patients is associated with an unfavourable long-term outcome. 1864 34

In the past 2 years, evidenced-based guidelines and statements on screening, diagnosis, and management of hepatitis B virus (HBV) from several organizations and experts have been published. The purpose of this article is to take the recommendations from these documents and help guide clinicians--whether they are primary care providers, hepatologists, gastroenterologists, or public health workers--about how to incorporate these guidelines into practice. The first task is for all providers to be involved in identifying persons with chronic HBV infection (CHB). New recommendations from the Centers for Disease Control and Prevention (CDC) advocate screening for the HBV in those at highest risk, especially persons from countries where HBV is endemic. Using information from the clinical and laboratory evaluation of the patient infected with HBV, especially the hepatitis B e antigen/antibody status, clinicians can classify the patient into 1 of the 4 phases of HBV infection. Because CHB is a dynamic process and patients can move from inactive to active infection status, and vice versa, all patients must be followed with alanine aminotransferase (ALT) and aspartate aminotransferase monitoring every 3 to 12 months for life. Those with elevated ALT and HBV DNA levels (>2,000 IU/mL) should be referred to a specialist for evaluation for possible treatment. Patients selected for antiviral therapy with nucleoside analogues should be followed every 3 to 6 months to detect emergence of antiviral resistance to the agent chosen. In addition, alpha-fetoprotein should be tested and ultrasound performed on all men aged >40 years and women >50 years of age to detect any hepatocellular carcinoma (HCC) in an early stage. Algorithms are included for primary care providers providing information on initial evaluation and management and referral of persons with CHB, and for specialists evaluating and treating HBV. Implementing steps to identify, follow, refer, and treat appropriately persons with CHB infection by all primary care and specialist healthcare providers can have a major impact on reducing the occurrence of HCC and cirrhosis in infected persons.
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PMID:Implementing evidenced-based practice guidelines for the management of chronic hepatitis B virus infection. 1918 74

Worldwide, 350 million people are chronically infected with hepatitis B virus (HBV) who are at greater risk of hepatocellular carcinoma (HCC) compared with uninfected people. The relative risks of HCC among people infected with HBV ranges from 5 to 49 in case-control studies and from 7 to 98 in cohort studies. More than 50% of HCC cases worldwide and 70-80% of HCC cases in highly HBV endemic regions are attributable to HBV. Incidence of HCC (per 100,000 person/year) among people with chronic HBV infection ranges from 400 to 800 in male and from 120 to 180 in female. Factors associated with increased risk of HCC include demographic characteristics (male sex and older age), lifestyles (heavy alcohol consumption and smoking), viral factors (genotype C, D F, high level of HBV DNA, core/precore mutation) and clinical factors (cirrhosis, elevated alpha-fetoprotein (AFP) and alanine aminotransferase (ALT)). HBV-related HCC has extremely poor prognosis with median survival less than 16 months. Survival rates of HBV-related HCC ranged from 36% to 67% after 1 year and from 15% to 26% after 5 year of diagnosis. Older age, liver function impairment, vascular invasion, tumour aggressiveness and elevated AFP are associated with HCC survival. Global burden of HBV-related liver disease is still a major challenge for public health in the 21st century. While decreases in incidence of HBV infection have been observed in birth cohorts following the introduction of universal infant HBV vaccination programme, HBV-related HCC incidence in is projected to increase for at least two decades because of the high prevalence of chronic HBV infection and prolonged latency to HCC development. To reduce HBV-related HCC continued expansion of universal infant HBV vaccination is required along with antiviral therapy targeted to those individuals at highest risk of HCC. Broad public health strategies should include routine testing to identify chronic HBV infection, improved health infrastructures including human resource to provide diagnosis and treatment assessment.
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PMID:Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. 1930 35

Perivascular epithelioid cell (PEC) tumors (or PEComas) are myomelanocytic lesions defined by coexpression of melanocytic and muscle markers, suggesting dual differentiation. They are rare mesenchymal tumors and include subtypes with distinct clinical features: angiomyolipoma, lymphangioleiomyomatosis, and clear cell "sugar" tumors of the lung, pancreas and uterus. Consequent upon the World Health Organization's recognition of PEC-derived tumors as a distinct entity, an increasing number of reports has documented PEComas arising at various anatomical locations. Clear cell myomelanocytic tumors of the falciform ligament/ligamentum teres (CCMTs) represent a rare variant of the PEComas. These hepatic PEComas, different from angiomyolipoma of the liver, pose a clinical, radiological and morphological diagnostic challenge. Because of their rarity, the clinical features and biological behavior of these tumors have yet to be established. We experienced our first case of CCMT in a 36-year-old woman who presented to our emergency department with a 3-day history of abdominal discomfort and progressive growth of an epigastric bulk. Intralesional hemorrhage was causing abdominal distension, which progressed to acute abdomen soon after. The hemoglobin concentration was 9.9 g/dL. Liver laboratory tests showed slight elevation of AST, ALT and gamma-GT. The alpha-fetoprotein level was not elevated. The radiological images showed a hemorrhagic mass with some bizarre features in left hepatic lobe, immediately adjacent to the ligamentum teres and falciform ligament. The patient underwent a left hepatic lobectomy. The diagnosis of CCMT was based on histological and immunohistochemical staining. The postoperative course was uneventful. The patient received no adjuvant treatment and is currently, 34 months after surgery, alive and disease free. In this report we describe a peculiar and hitherto undescribed clinical presentation of this tumor and its further course. Moreover, we discuss previously undescribed diagnostic imaging. We recommend that all unusual carcinomas and mesenchymal tumors of the liver should be tested for HMB-45: when positive, there is a high likelihood of PEComa.
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PMID:Acute abdomen as an unusual presentation of hepatic PEComa. A case report. 1936 72


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