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)

L-689,502, N-[2(R)-hydroxy-1(S)-indanyl]-5(S)-(1,1-dimethylethoxy- carbonylamino)-4(S)-hydroxy-6-phenyl-2(R)-(4-[2-(4- morpholinyl)ethoxy]phenyl)methyl hexanamide, is a potent inhibitor of human immunodeficiency virus-1 protease. The effect of dose on the elimination kinetics of L-689,502 was studied in rats and dogs. After i.v. administration, total plasma clearance of L-689,502 in rats decreased with increasing dose; the clearance decreased from 181 ml/min/kg at 1 mg/kg to 86 ml/min/kg at 20 mg/kg. Similar results were observed in dogs; clearance fell from 29 ml/min/kg at 0.5 mg/kg to 17 ml/min/kg at 10 mg/kg. Bile flow in rats was retarded in a dose-dependent manner after a single i.v. injection of L-689,502. The cholestatic effect was reversible and maximal at 5 mg/kg i.v. Consistent with the cholestatic effect, L-689,502 caused an increase in serum levels of aminotransferase. After i.v. administration of L-689,502 (10 mg/kg), alanine aminotransferase increased from 50 to 370 IU/liter and aspartate aminotransferase from 120 to 700 IU/liter. Moreover, pretreatment of rats with L-689,502 resulted in a significant decrease in the elimination kinetics of antipyrine and diflunisal, as well as of L-689,502 itself. Collectively, these results suggest that the dose-dependent kinetics of L-689,502 in rats and dogs are more likely due to hepatotoxicity caused by the drug than to capacity-limited metabolism.
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PMID:Dose-dependent toxicokinetics of L-689,502, a potent human immunodeficiency virus protease inhibitor, in rats and dogs. 140 75

The risk of non-A, non-B hepatitis transmission by an intravenous immunoglobulin (IVIG) preparation was assessed in a prospective multicenter trial in 68 patients with primary immunodeficiency disorders (40 children or adolescents and 28 adults). During the 4-week prestudy evaluation period the clinical examinations and liver function tests including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin were normal in all patients. The treatment consisted of three infusions of 200 mg IVIG (pH 4; pepsin procedure) per kilogram body weight at 2-week intervals. During the observation period of 24 weeks following the first infusion of the study IVIG, the patients were monitored at regular time intervals. No clinical and laboratory signs of hepatitis or liver dysfunction were noticed. All patients completed the study. In 5 patients, one isolated alanine aminotransferase value and in another patient one gamma-glutamyl transpeptidase value were moderately elevated, but always below 2.5 times the upper limit of the reference range. Similar isolated and transient elevations were observed for aspartate aminotransferase and alkaline phosphatase. It was concluded that the IVIG preparation did not transmit non-A, non-B hepatitis or other viral liver diseases.
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PMID:Safety of intravenous immunoglobulin preparations: a prospective multicenter study to exclude the risk of non-A, non-B hepatitis. 177 40

Several randomised controlled trials have been undertaken to evaluate the efficacy of alpha-interferon in the therapy of chronic hepatitis B. In patients with HBe antigen-positive disease acquired in adult life the response rates vary from 25-50%. In those infected at birth, response rates are lower. Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti-human immunodeficiency virus antibody status (p less than 0.001), chronic active hepatitis on liver biopsy (p less than 0.005), high AST level (p less than 0.001), low hepatitis B virus DNA level (p less than 0.001) and a history of acute hepatitis (p less than 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p less than 0.05). The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter, which predicted response in 77% with a specificity of 79% (p less than 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration (p less than 0.001).
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PMID:Treatment of hepatitis B virus infection with interferon. Factors predicting response to interferon. 196 Mar 78

A 71-yr-old male presented with a 2-month history of fever, malaise, and weight loss. Physical exam revealed chorioretinitis. Laboratory studies were notable for elevated levels of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate transaminase, and alanine transaminase. Immunoglobulin G antibody to Toxoplasma gondii was positive to a dilution of 1:4096, whereas serologic studies for hepatitis A virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, Brucella, and Tularemia were negative. A percutaneous biopsy of the liver revealed hepatic granulomas. Culture of the biopsy specimen was negative for growth of mycobacteria or fungi. Spontaneous improvement in clinical and laboratory parameters occurred over a 4-month period.
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PMID:Toxoplasmic chorioretinitis and hepatic granulomas. 222 Jul 41

Virus inducible elements (IE) in promoters of mouse alpha-interferon and human beta 1-interferon genes contain multiple copies of the hexanucleotide sequence AGT-GAA or its variants which are also found in the interferon-stimulated response element of genes transcriptionally induced by interferon. We have examined the similarities between virus and interferon induction of gene expression and the role of AGTGAA and AAT-GAA hexamers in these responses. Hybrid plasmids were constructed by inserting the IE region, the alpha 4 promoter, or the multiple copies of AGTGAA or AAT-GAA 5' to the inactive-45 human immunodeficiency-chloramphenicol acetyltransferase hybrid gene, and their inducible expression was studied in a transient expression assay. In L-cells, multiple hexamers were efficiently induced both by infection with Newcastle disease virus and by interferon treatment; while the alpha 4 promoter and the IE inducible region were induced predominantly by virus rather than by interferon. In order to dissociate the effect of virus and endogenous interferon on the induction process, we examined the gene expression in Vero cells, which have undergone homozygous deletion of type 1 interferon genes, and in VNPT-159 cells, which were derived from Vero cells by insertion of an inducible human interferon beta 1 gene. The results show that while the alpha 4 promoter was efficiently induced only by virus in both cell types, the constructs containing shorter segments of the IE were induced by both virus and interferon in Vero cells. However, the inducibility by interferon was not detected in VNPT-159 cells, suggesting that the presence of endogenous interferon suppresses interferon-induced expression of hexanucleotide repeats and the short inducible region. In contrast, virus inducibility of endogenous interferon-stimulated genes, ISG-15 and ISG-54, was about 100-fold more efficient in VNPT-159 cells than in Vero cells, suggesting that this induction is largely mediated through synthesis of endogenous interferon. Hence, endogenous interferon may play a role in the autoregulation of both interferon genes and interferon-stimulated genes.
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PMID:Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation. 255 Apr 51

Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti-human immunodeficiency virus antibody status (p less than 0.001), chronic active hepatitis on liver biopsy (p less than 0.005), high AST level (p less than 0.001), low hepatitis B virus DNA level (p less than 0.001) and a history of acute hepatitis (p less than 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p less than 0.05). The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter, which predicted response in 77% with a specificity of 79% (p less than 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration (p less than 0.001).
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PMID:Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy? A statistical analysis of predictive factors. 237 80

We studied unselected, hepatitis B surface antigen (HBsAg)-positive parenteral drug abusers for antibody to hepatitis D virus (anti-HD) and antibody to human immunodeficiency virus (HIV). The prevalences of anti-HD and antibody to HIV were 67% and 58%, respectively, and there was no association between positivity for these two markers. In a logistic regression model, anti-HD was associated with older age (P = .001), longer duration of drug abuse (P = .045), and the presence of liver disease (P = .002). Antibody to HIV was associated with a younger age (P = .003) and increased serum globulin levels (P less than .001). In patients infected with HIV, the severity of hepatic dysfunction remained correlated with anti-HD. In anti-HD-positive patients, most indices of hepatic dysfunction were similar whether or not antibody to HIV was present, but serum aspartate aminotransferase levels were significantly higher in patients with both anti-HD and antibody to HIV. (124 +/- 16 vs. 74 +/- 11, P less than .05).
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PMID:Hepatitis D virus and human immunodeficiency virus antibodies in parenteral drug abusers who are hepatitis B surface antigen positive. 317 Dec 27

We measured serum aspartate transaminase (AST) concentration and serum hepatitis B virus (HBV) DNA concentration in homosexual men with chronic HBV infection and a spectrum of immune deficiency as a result of exposure to human immunodeficiency virus (HIV). Serum AST and HBV DNA concentrations were similar in patients with varying immune function as indicated by in vivo criteria (diagnosis and skin tests reactivity) and in vitro criteria (lymphocyte transformation responses to mitogens and Candida and tetanus antigens) and were unrelated to the number of circulating T cells, suppressor/cytotoxic cells, helper cells, natural killer cells, and the helper:suppressor ratio. Serum AST concentration and indices of cellular immune function were similar in patients with varying HBV replicative activity (high and low HBV DNA concentrations). The observed lack of relationship between serum AST concentration and indices of cellular immune function and HBV replication suggests either that other factors determine the severity of hepatic inflammation in chronic HBV infection, or that currently available tests of cellular immune function and HBV replicative activity do not accurately reflect processes in the liver.
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PMID:Hepatic inflammation, hepatitis B replication, and cellular immune function in homosexual males with chronic hepatitis B and antibody to human immunodeficiency virus. 334 28

For identification of the features of disseminated Mycobacterium avium complex (DMAC) in human immunodeficiency virus (HIV)-infected children, a retrospective medical record review of 31 long-term survivors with transfusion-acquired HIV was conducted. Nine patients developed DMAC defined as positive isolation of M. avium complex from peripheral blood. DMAC was diagnosed in patients 51 to 132 months of age (mean, 101). The time from HIV-infecting transfusion to DMAC diagnosis ranged from 37 to 132 months (mean, 92) and survival from the time of DMAC diagnosis ranged from 4 to 21 months (mean, 10). Selected laboratory and clinical measures in DMAC-positive and DMAC-negative subjects were compared. DMAC-positive patients had significantly lower CD4+ T cell counts and higher HIV p24 antigen concentrations than DMAC-negative patients at comparable times. Increased percentages of circulating leukocyte band forms and increased aspartate aminotransferase values were seen more often in DMAC-positive patients. Fever and abdominal pain were the only clinical features seen more often in DMAC-positive than in DMAC-negative patients. At the end of the study period overall survival of DMAC-positive patients was less than that of DMAC-negative children, at 33% vs. 73%. DMAC occurs in profoundly immunocompromised children with advanced HIV disease and significantly affects survival. The clinical and laboratory features of DMAC are relatively nonspecific and a high index of suspicion in patients with markedly reduced CD4+ T cells is essential.
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PMID:A comparative study of transfusion-acquired human immunodeficiency virus-infected children with and without disseminated Mycobacterium avium complex. 791 34

Variable regions with sequence length variation in the human immunodeficiency virus type 1 envelope exhibit an unusual pattern of codon usage with AAT, ACT, and AGT together composing > 70% of all codons used. We postulate that this distribution is caused by insertion of AAT triplets followed by point mutations and selection. Accumulation of the encoded amino acids (asparagine, serine, and threonine) leads to the creation of new N-linked glycosylation sites, which helps the virus to escape from the immune pressure exerted by virus-neutralizing antibodies.
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PMID:Insertion of N-linked glycosylation sites in the variable regions of the human immunodeficiency virus type 1 surface glycoprotein through AAT triplet reiteration. 793 44


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