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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To analyze the serological, clinical and histological significance of hepatitis B virus (HBV) replication among a group of patients with chronic delta hepatitis (CDH), we have studied the clinical and the histological activity in 49 patients with CDH. The HBV-DNA was analyzed by dot-blot and polymerase chain reaction (PCR). Concomitant infection with hepatitis C virus (HCV) was analyzed by reverse transcriptase (RT)-PCR, HDV replication by dot-blot, and human immunodeficiency virus (HIV) infection by enzyme-linked immunosorbent assay. The subjects were divided into three groups according to HBV-DNA status: group I: 14 patients HBV-DNA dot-blot positive; group II: 29 patients HBV-DNA positive only by PCR, and group III: 6 patients HBV-DNA negative by dot-blot and PCR. We have found HBV-DNA by dot-blot in 28.5% of patients, and by PCR in 87.7%. Also 22 patients were anti-HCV positive (86.3% had HCV-RNA by RT-PCR). The first group (HBV-DNA dot-blot positive) had significantly higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than those in the second and third groups. Likewise, serum ALT and AST were significantly higher in the second group (HBV-DNA positive by PCR) than in those of the third group. Histological inflammatory activity was significantly higher in the group of patients with HBV-DNA detectable by dot-blot. The prevalence of serum HDV-RNA and IgM anti-HDV were similar in the three groups. These results were similar in the anti-HCV-positive and -negative patients. In conclusion, these data suggest that: (1) persistence of HBV replication is a major determinant of severe liver damage in chronic delta hepatitis, and (2) HCV and HIV infections do not influence the natural history of CDH.
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PMID:Correlation between hepatitis B viremia and the clinical and histological activity of chronic delta hepatitis. 799 89

We have previously observed an increased frequency of liver failure in human immunodeficiency virus (HIV)-infected hemophiliacs. The purpose of this study was to quantitate hepatitis C virus (HCV) RNA levels in serial samples from HIV-seropositive (HIV+) and HIV-seronegative (HIV-) hemophiliacs before and after HIV seroconversion, and to examine the relationship of HCV RNA levels to CD4 cell counts and to hepatic dysfunction over time. HCV RNA levels were measured on serial samples of serum stored frozen from 17 HCV+/HIV+ and 17 HCV+/HIV- subjects matched within 5 years of their birth dates. All were HCV+ before study entry. HCV RNA levels were quantitated by a branched DNA-enhanced label amplification (bDNA) assay. For samples less than the cut off, HCV RNA was measured by the nested polymerase chain reaction. Individual changes over time, clinical groups, and mean values within predetermined time windows were compared with Wilcoxon rank sum tests. Mean HCV RNA levels increased from 2.76 (standard error [SE] 1.33) x 10(5) to 2.84 (SE 1.39) x 10(6) eq/mL during the first 2 years after HIV seroconversion (P = .006). Baseline HCV RNA levels in the pre-HIV seroconversion group were not significantly different from the baseline levels in those who remained HIV (P = .79). Over the entire period of study, HCV RNA levels increased nearly threefold in those who remained HIV- (mean 9.47 [SE 4.78] x 10(5) to 2.81 [SE 1.13] x 10(6)/mL; P = .02). Among those who became HIV+, HCV RNA levels increased 58-fold (mean 2.85 [SE 1.26] x 10(5) to 1.66 [SE 0.57] x 10(7) eq/mL; P = .0001). The rate of increase in HCV RNA levels was eightfold faster for HIV+ subjects than for subjects who remained HIV- (P = .009). HCV RNA levels increased twofold higher in 5 subjects who developed liver failure compared with the 12 who did not (P = .43). HCV RNA levels correlated significantly with CD4 counts (R = -.33, P = .01) and serum aspartate aminotransferase levels (AST) (R = .36, P = .007). We conclude that HCV RNA levels are significantly higher in HIV+ than in HIV- multitransfused hemophiliacs. HCV load increases over time, is enhanced by HIV, and further increases as immune deficiency progresses. HCV RNA levels are directly associated with high AST levels. These findings suggest that HIV-induced immune deficiency may promote increased HCV replication.
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PMID:Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. 804 20

An antisense phosphorothioate oligodeoxynucleotide 27-mer complementary to the rev gene mRNA of the human immunodeficiency virus (HIV-1) was administered to rats through intravenous injections and subcutaneous infusions in order to investigate the disposition of this compound. In addition, nonlethal toxic responses of the rat were evaluated. A biphasic plasma clearance with t1/2 alpha of 20-25 min and t1/2 beta of 27-41 hr was observed. Single doses ranging from 35 to 3257 micrograms were examined, and the plasma concentration and area under the plasma concentration-time curve (AUC) were found to be directly proportional to the dose. Continuous subcutaneous infusion of 50 mg over 28 days was also examined. The oligonucleotide is completely eliminated in the urine over 3 days. Electrophoretic analysis demonstrated that the excreted compound has the same mobility and UV-absorbance profile as the administered compound. Measurement of accumulation and distribution into tissues revealed unique tissue-specific rates and extent of oligonucleotide movement into and out of tissues. Results of the chronic infusion study suggest that uptake into tissue is not saturated, even after 28 days of infusion. Analysis of blood plasma from oligonucleotide-treated animals shows a possible transient elevation in levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), but not alkaline phosphatase (AP), gamma-glutamyltransferase (GT), and bilirubin. The data collectively support the potential utility of phosphorothioate oligonucleotides as therapeutic agents in vivo.
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PMID:Pharmacokinetics of an antisense phosphorothioate oligodeoxynucleotide against rev from human immunodeficiency virus type 1 in the adult male rat following single injections and continuous infusion. 806 15

A distinct clinical syndrome of cholestasis and hepatitis occurred during early infancy in seven infants with perinatally acquired human immunodeficiency virus 1 infection. In five infants hepatitis was the first manifestation of human immunodeficiency virus 1 infection. The median age of onset of hepatitis was 7 months (range, 5 to 10 months). The mean total bilirubin concentration at presentation was 7.4 mg/dl (range, 3.9 to 11 mg/dl), the mean aspartate aminotransferase was 1512 IU/liter (range, 782 to 2960 IU/liter) and the mean alanine amino-transferase 512 IU/liter (range, 92 to 1247 IU/liter). The absolute CD4 count at the time of onset of hepatitis ranged from 191 to 2298 cells/mm3 (mean, 766 cells/mm3). Six of the seven children died within 12 weeks of onset of hepatitis, three as a result of complications of Pneumocystis carinii pneumonia, and two died of complications secondary to cytomegalovirus. In only one infant was the cause of death the direct consequence of liver failure. The seventh infant died 17 months after the onset of hepatitis of dilated cardiomyopathy. No specific etiologic agent has been identified as the cause of cholestatic hepatitis in these infants. In situ hybridization studies to detect human immunodeficiency virus 1 messenger RNA was negative in the liver tissue obtained at biopsy and autopsy in five of the samples tested.
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PMID:Cholestatic hepatitis in children infected with the human immunodeficiency virus. 810 98

Light-activated merocyanine 540 (pMC540) has been shown in our earlier studies to be effective against certain types of tumor cells and viruses, including human immunodeficiency virus (HIV-1). To test the potential extracorporeal and systemic use of pMC540, its toxicity was investigated in DBA/2 mice, pigs, and dogs. The lethal dose in DBA/2 mice after an i.p. injection was 370 mg/kg, and the 50% lethal dose (LD50) was 320 mg/kg; however, following i.v. administration, the lethal dose and the LD50 dose were 240 and 160 mg/kg, respectively. Tritium-labeled MC540 was used to study the biodistribution of pMC540 in DBA/2 mice. Almost 70% of the injected radioactivity was excreted within 6 h of injection. After 1 week, the pMC540 was almost completely cleared, with only 1.89% of the activity remaining, and had a plasma half-life of 23 h. Pigs injected with an accumulated dose of 10 mg/kg and followed for a period of 30 days did not show adverse signs of toxicity as monitored by SMAC-28 analysis, CBC profile, and blood-coagulation studies. A dog injected with a single dose of 20 mg/kg showed induction of the hepatic enzymes glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (AST); however, serum levels of gamma-glutamyl transpeptidase (GGT) remained unchanged. The data presented herein may serve to identify certain drug-dose limitations in the systemic use of pMC540.
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PMID:Biodistribution and toxicity of photoproducts of merocyanine 540. 845 86

In about 30% to 40% of patients with chronic hepatitis C, treatment with recombinant interferon alfa (r-IFN alpha) causes a decrease of serum aminotransferases and hepatitis C virus (HCV) RNA. The antiviral mechanism of interferon alfa (IFN alpha) in vivo is unknown. From serial measurements of serum HCV-RNA concentrations following IFN alpha induced perturbation of the balance between virus production and clearance, we obtained kinetic information on the pretreatment steady-state of HCV. In patients with chronic hepatitis C responding to IFN alpha, HCV-RNA declined exponentially with a half life of approximately 2 days. Modeling of the data predicts that in patients with chronic hepatitis C responding to IFN alpha this cytokine predominantly acts as an inhibitor of de novo infection of susceptible cells. HCV is released from infected cells with a mean half life of 2.7 +/- 1.3 days, whereas the clearance rate from serum is faster (mean half life, 0.7 +/- 0.4 days). The minimum virus production and clearance per day in patients with chronic hepatitis C was calculated to be 6.7 x 10(10) virions/d (range, 0.2 to 43.8 x 10(10) virions/d). These values showed no correlation with the HCV genotype, aminotransferase levels, or the histological activity as assessed before the administration of r-IFN alpha. Simultaneous kinetic analysis of serum aminotransferases as surrogate markers of hepatocyte integrity revealed half lifes for the release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from hepatocytes of 4.7 +/- 3.8 and 3.0 +/- 3.5 days, respectively. The half life data for HCV in chronically infected patients are remarkably similar to recently published data on human immunodeficiency virus type 1 (HIV-1) suggesting that both RNA viruses replicate continuously and highly productive in vivo. The turnover rates explain the rapid generation of viral diversity and the opportunity for viral escape phenomena from the host immune surveillance.
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PMID:Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo. 859 65

A retrospective analysis of 99 hepatitis B-positive homosexual men with known human immunodeficiency virus (HIV) status was conducted to study the interaction of concurrent HIV infection on the course of their chronic hepatitis B virus (HBV) infection. All 99 subjects had chronic hepatitis B, 43 of whom were HIV antibody negative and 56 of whom were HIV antibody positive at the time of their initial presentation. Serial serum aminotransferase levels were used as an indirect estimate of the severity of hepatic inflammation. Factors that may influence the course of hepatitis B, HIV status, hepatitis B e antigen (HBeAg)/hepatitis B e antibody (HBeAb) status, alcohol intake, and zidovudine (AZT) therapy were correlated with aminotransferase values. Overall, there was no difference in mean serum alanine aminotransferase (ALT) levels between HIV antibody-negative and HIV antibody-positive patients. There is a higher prevalence rate of HBeAg in HIV antibody-positive patients (p < 0.05), and the seroconversion rate from HBeAg to HBeAb was lower in HIV antibody-positive patients compared with HIV antibody-negative patients (p < 0.05). However, reactivation rates from HBeAb to HBeAg were no different in the HIV antibody-positive and negative hepatitis B carriers. With mild, moderate, or heavy alcohol intake, we observed no statistically significant difference in mean serum alanine aminotransferase levels and no mean serum aspartate aminotransferase levels between HIV antibody-negative patients versus HIV antibody-positive patients. Similarly, there was no significant difference in the pattern of serum aminotransferase in those subjects treated with or without AZT. The mortality rates were higher in HIV antibody-positive patients (n = 8) compared with in HIV antibody-negative patients (n = 2). Seventy-five percent (n = 6) of the HIV antibody-positive patients died from acquired immunodeficiency syndrome (AIDS), and overall only two patients died of liver disease, one in each group. We conclude that there is no overt influence by HIV or the treatment thereof on the course of chronic HBV infection in a population of homosexual men. In HIV-infected patients, death from AIDS predominated; hence, the main target for therapy should be HIV rather than HBV.
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PMID:The interaction of human immunodeficiency virus infection and hepatitis B virus infection in infected homosexual men. 877 27

The compound 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent inhibitor of a number of viruses in vitro such as human immunodeficiency virus types 1 and 2, herpes simplex virus types 1 and 2, hepatitis B virus, cytomegalovirus, and Epstein-Barr virus. PMEA also proved to be effective in vivo against feline immunodeficiency virus in cats and simian immunodeficiency virus in rhesus monkeys. In an open, non-placebo-controlled trial, the safety of weekly doses of PMEA in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was studied for a period of 11 weeks. CD4+ T-cell counts at baseline were between 10 and 450/mm(3). The drug was administered intravenously at a dose of 1000 mg. No serious side-effects were seen. On one occasion one patient showed alanine aminotransferase and aspartate aminotransferase levels 5 times higher than the upper limit of normal and another patient showed on one occasion aspartate aminotransferase levels 5 times higher than the upper limit of normal. In another patient serum amalyse levels increased, on one occasion 1.5 times above the upper limit of normal. An improvement in general well-being was reported by all patients. For patients with a CD4+ T-cell count > 100/mm(3) at baseline, the CD4+ T-cell count increased from a mean of 283/mm(3) at baseline to a mean of 448/mm(3) at the end of the study. Repeat infusions of PMEA at a dose of 1000 mg were safe and well tolerated. Our results suggest that PMEA, administrated according to this treatment schedule, may be effective in treating patients with human immunodeficiency virus infection.
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PMID:Safety of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in patients with human immunodeficiency virus infection: a pilot study. 886 29

After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years under identical conditions. Blood samples were analyzed for the following: complete hematology, clinical chemistry, serum protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets. The following hematological and clinical chemistry parameters were markedly changed in the FIV-infected animals from month 9 onwards: glucose, serum protein, gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride. In FeLV infection, the markedly changed parameters were mean corpuscular volume, mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to reports of field studies, neither FIV-positive nor FeLV-positive animals developed persistent leukopenia, lymphopenia, or neutropenia. A significant decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+ and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection. The changes in FIV infection may reflect subclinical kidney dysfunction, changes in energy and lipid metabolism, and transient activation of the humoral immune response as described for human immunodeficiency virus (HIV) infections. The changes in FeLV infection may also reflect subclinical kidney dysfunction and, in addition, changes in erythrocyte and immune function of the animals. No severe clinical signs were observed in the FIV-positive cats, while FeLV had a severe influence on the life expectancy of persistently positive cats. In conclusion, several parameters of clinical chemistry and hematology were changed in FIV and FeLV infection. Monitoring of these parameters may prove useful for the evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many parallels between laboratory parameters in FIV and HIV infection further support the importance of FIV as a model for HIV.
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PMID:Parameters of disease progression in long-term experimental feline retrovirus (feline immunodeficiency virus and feline leukemia virus) infections: hematology, clinical chemistry, and lymphocyte subsets. 900 78

Ten patients with asymptomatic human immunodeficiency virus (HIV) infection were treated for typhoid fever at King Edward VIII Hospital, Durban, South Africa, from 1993 through 1995. The mean age was 23.7 years (range, 8-33 years), with a female-to-male ratio of 9 to 1 and mortality and morbidity rates of 20% and 10%, respectively. Common presenting manifestations were fever (100%), relative bradycardia (50%), and diarrhea (40%). With respect to epidemiologic and clinical characteristics, we noted no significant differences among these 10 HIV-positive and 32 HIV-negative patients treated for typhoid fever during the same period. However, we found hepatic dysfunction in the form of an isolated increase in aspartate aminotransferase (p < 0.01) and abnormal urinary findings suggestive of glomerulonephritis (p = 0.01) more frequently in HIV-positive patients.
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PMID:Typhoid fever and asymptomatic human immunodeficiency virus infection. A report of 10 cases. 941 66


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