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)

One hundred thirty-two cases of severe acetaminophen (paracetamol) poisoning were treated with oral methionine. Seven of 96 patients who received the antidote within ten hours of ingestion of the overdose had severe liver damage (aspartate transaminase level, greater than 1,000 IU/L), but none of these patients died. Thirty-six patients received methionine between ten and 24 hours of ingestion; severe liver damage occurred in 47%, and two patients died. The treatment protocol for oral methionine is simple, and therapy is complete within 12 hours as compared with three days for oral acetylcysteine and 20 hours for intravenous acetylcysteine. Side effects from methionine were unimportant. Oral methionine is as effective as acetylcysteine in preventing severe liver damage and death after acetaminophen overdose. However, as with acetylcysteine, it must be given within ten hours of ingestion to be effective.
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PMID:Treatment of acetaminophen poisoning. The use of oral methionine. 746 32

We investigated whether S-adenosyl-L-methionine (SAMe) influences the inhibitory effect of ethanol on bile secretion and ethanol hepatotoxicity in the isolated perfused rat liver. SAMe (25 mg/kg intramuscularly three times a day) was administered for three days consecutively. Liver was then isolated and perfused with taurocholate to stabilize bile secretion and exposed to 1% ethanol for 70 min. The effect of ethanol on bile flow, bile salt biliary secretion, oxygen liver consumption, AST and LDH release in the perfusate, and hepatic concentration of glutathione, malondialdehyde, and diene conjugates was compared between SAMe-treated livers (N = 11) and paired controls (N = 11). Control experiments without ethanol were also performed (N = 6). Exposure to 1% ethanol induced a significantly (P < 0.03) higher inhibition of bile flow (-35% vs 17%) and bile salt secretion (-28% vs 16%) in untreated compared with SAMe-treated livers. During 1% ethanol exposure, the release of LDH and AST in the perfusate was significantly lower (P < 0.02) in SAMe-treated livers. Oxygen liver consumption was markedly inhibited by 1% ethanol administration (P < 0.02 vs controls without ethanol), an effect almost totally prevented by SAMe treatment (P < 0.02 vs ethanol controls). The hepatic concentration of total glutathione was significantly (P < 0.02) decreased by 1% ethanol exposure, but this effect was less pronounced in SAMe-treated than in untreated controls (P < 0.02). The hepatic levels of malondialdehyde and diene conjugates were not significantly changed by ethanol exposure in either SAMe-treated or control livers in comparison to ethanol-free controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of S-adenosyl-L-methionine on ethanol cholestasis and hepatotoxicity in isolated perfused rat liver. 762 90

Despite the extensive search for disease causing mutations in exons 28-36 of the neurofibromatosis type 1 (NF1) gene, the NF1 specific mutations so far documented account for only a small proportion of all NF1 cases. In this study, we have used 8 sets of new primers to amplify sequences throughout the NF1 gene, including 10 different exons and their flanking intron sequences. The derived PCR products from 150 independent NF1 patients and 50 normal controls were examined by heteroduplex analysis on Hydrolink gels. Three novel mutations were identified and characterised. Two of these mutations include the same 3-bp deletion (AAT) within exon 17 with a silent codon change from ACA (threonine) to ACG (threonine) and a loss of the codon ATG (methionine). The third mutation is a 10-bp deletion (TTCTCTTGGA) within exon 44 resulting in the formation of an inappropriate stop codon. These results should be useful for the further elucidation of the molecular basis of NF1.
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PMID:Neurofibromatosis type 1 (NF1): the search for mutations by PCR-heteroduplex analysis on Hydrolink gels. 790 9

Sixteen Escherichia coli clinical isolates which were resistant to ampicillin and amoxicillin-clavulanate but susceptible to cephalothin were studied. Eight strains showed the presence of a beta-lactamase which comigrates with reference OXA-1 enzyme. The eight other strains produced different TEM-1 derivatives which had in common a higher Km for penicillins and a higher 50% inhibitory concentration for the beta-lactamase inhibitors. By oligotyping and sequencing of PCR products, it was shown that Ser (AGC) (TEM-30; also called TRI-1) in three strains and Cys (TGC) (TEM-31; also called TRI-2) in one strain were substituted for Arg-241 (CGC), that Leu (CTG) (TEM-33) and Val (GTG) (TEM-34) in one strain each were substituted for Met-67 (ATG), and that in other mutants the two latter substitutions occurred together with the substitution of Asp (GAT) (TEM-35 and TEM-36) for Asn-272 (AAT). Therefore, different sets of amino acid substitutions of TEM-1 can be found in clinical isolates and lead to resistance to beta-lactamase inhibitors.
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PMID:Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 beta-lactamase conferring resistance to beta-lactamase inhibitors. 806 42

Serum amino acid (AA) profiles are altered in epilepsy. It is not clear whether this is due to the disease process itself or to other variables such as seizure type, seizure frequency, duration of illness, medication, or altered liver function. We investigated serum AA profiles and liver enzymes in 73 epileptic patients and 90 healthy subjects and evaluated the data by analysis of variance to discriminate between age, sex, seizure type, duration of illness, seizure frequency, antiepileptic drug (AED) and increased serum liver enzyme levels, and their putative interaction with the serum AA profile. There was no correlation between the changes in the AA profile and age, duration of illness, seizure frequency, and seizure type. Seventy-two percent of the AED-treated patients and 33% of the unmedicated patients showed an increase in one or several serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or gamma-glutamyl transferase (gamma-GT)]; particularly gamma-GT. We observed a significant increase in serum concentrations of glutamine and glycine and decreased levels of taurine, threonine, serine, valine, methionine, isoleucine, leucine, phenylalanine, histidine, tryptophan, and arginine in AED-treated patients but not in unmedicated patients. These results show that the changes in the serum AA profiles of epileptic patients treated with AEDs occur in patients with alteration of serum liver enzymes; whether this implies a causal relation is still uncertain.
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PMID:Serum amino acids, liver status, and antiepileptic drug therapy in epilepsy. 809 92

Serum lactate dehydrogenase (LDH) isoenzyme and amino acid (a.a) patterns were evaluated in comparison to several other biochemical parameters for liver and renal function with the objective of clarifying the differential diagnosis of hepatic disorders and predicting the outcome of schistosomal infection in Egyptian patients. Patients examined included those with complicated hepatic disorders and others with different stages of schistosomal infestation, hepatoma or bladder cancer, in addition to a normal control group. Several biochemical parameters appeared to be useful in establishing consistent differences or similarities between the studied groups. Examples are; elevated serum AST/ALT ratio and methionine content in chronic schistosomiasis, elevated serum urea/creatinine ratio and leucine content in all schistosomal patients and extremely high levels of N-acetyl-beta-D-glucosaminidase (NAG) in the urine of non-schistosomal bladder cancer patients. In addition, characteristic LDH isoenzyme profiles distinguish between the studied groups, in particular separating chronic schistosomiasis from schistosomal bladder cancer and hepatoma from other hepatic disorders.
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PMID:Diagnostic value of serum lactate dehydrogenase isoenzyme and amino acid patterns in several schistosomal and non-schistosomal disorders as compared to other biochemical parameters. 887 15

Six naturally occurring but rare alleles of sn-glycerol-3-phosphate dehydrogenase (Gpdh) in Drosophila melanogaster have been investigated in this study. They all belong to a class of GpdhUF (ultra-fast) alleles, because their electrophoretic mobilities are faster than that of the GpdhF (fast) allele. The GpdhUF variants are widespread, and have been reported from five continents. DNA sequence analysis has shown that the change in electrophoretic mobility was in each allele caused by a single amino acid residue substitution in the encoded protein. In the XiamenUF allele it is a substitution of lysine (AAA) to asparagine (AAT) in exon 1 (residue 3). An asparagine (AAT) to aspartate (GAT) change was found in exon 6 (residue 336) in the IowaUF and NetherlandsUF alleles. The mobility of the RaleighUF allele was altered by a valine (GTG) to glutamate (GAG) substitution in exon 3 (residue 76). Two mutations were detected in the BrazzavilleUF allele: a lysine (AAG) to methionine (ATG) substitution in exon 2 (residue 68) is responsible for the ultra-fast phenotype of this variant, while a tyrosine (TAT) to phenylalanine (TTT) substitution in exon 4 (residue 244) is not expected to alter the electrophoretic mobility of the encoded protein. These results indicate that the GpdhUF alleles originate from different mutational events, and only two of them--IowaUF and NetherlandsUF--might share a common ancestry. The GPDH activity of the IowaUF allele is intermediate between those of the GpdhS and GpdhF control stocks. The other GpdhUF variants have lower activities than the controls: XiamenUF--83%, RaleighUF--80% and BrazzavilleUF--73% of the GpdhF control.
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PMID:Molecular structure of rare but geographically widespread sn-glycerol-3-phosphate dehydrogenase 'ultra-fast' electrophoretic alleles in Drosophila melanogaster. 890 Nov 36

Eight myoinhibiting peptides were purified by high performance liquid chromatography from a methanolic extract of 7000 brains of the desert locust, Schistocerca gregaria. Complete sequences were obtained via a novel, combined approach employing: (1) chemical microsequencing and (2) post-source decay analysis on a reflectron time-of-flight mass spectrometer using matrix-assisted laser desorption/ionisation. Each of the peptides shows C-terminal amino acid sequence similarity to cockroach and cricket allatostatins and to blowfly callatostatins. Therefore, these novel peptides were designated Schistocerca gregaria allatostatins (Scg-ASTs) or schistostatins and their primary structures were determined to be: Ala-Tyr-Thr-Tyr-Val-Ser-Glu-Tyr-Lys-Arg-Leu-Pro-Val-Tyr-Asn-Phe-Gly-Leu- NH2 (Scg-AST-2), Ala-Thr-Gly-Ala-Ala-Ser-Leu-Tyr-Ser-Phe-Gly-Leu-NH2 (Scg-AST-3), Gly-Pro-Arg-Thr-Tyr-Ser-Phe-Gly-Leu-NH2 (Scg-AST-4), Gly-Arg-Leu-Tyr-Ser-Phe-Gly-Leu-NH2 (Scg-AST-5), Ala-Arg-Pro-Tyr-Ser-Phe-Gly-Leu-NH2 (Scg-AST-6), Ala-Gly-Pro-Ala-Pro-Ser-Arg-Leu-Tyr-Ser-Phe-Gly-Leu-NH2 (Scg-AST-7), Glu-Gly-Arg-Met-Tyr-Ser-Phe-Gly-Leu-NH2 (Scg-AST-8), and Ala-Pro-Ala-Glu-His-Arg-Phe-Ser-Phe-Gly-Leu-NH2 (Scg-AST-10). Synthetic Scg-AST peptides inhibit the peristaltic movements of the oviduct of S. gregaria. Although all eight peptides show potent inhibitory effects on juvenile hormone (JH) biosynthesis by corpora allata (CA) of the cockroach Diploptera punctata, no allatostatic effects were observed on CA of the desert locust (S. gregaria).
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PMID:Isolation and characterization of eight myoinhibiting peptides from the desert locust, Schistocerca gregaria: new members of the cockroach allatostatin family. 890 48

The possibility that postmortem biochemical changes in blood might parallel drug redistribution and thus serve as markers was explored in a detailed case study. Eighteen blood and 14 tissue and fluid samples were taken at autopsy 16 h after the death of a 34-year-old female from amitriptyline overdose. Ranges of drug concentrations in blood were amitriptyline 1.8 to 20.2 micrograms/mL, nortriptyline 0.6 to 7.3 micrograms/mL, levels were lowest in femoral vein and highest in pulmonary vein blood. Corresponding levels of 17 amino acids showed markedly different patterns of site-to-site variability. There was a strong positive correlation between individual amino acid and drug concentrations in pulmonary blood samples (n = 5), particularly for glycine, leucine, methionine, serine, and valine. In blood samples from the great veins and right heart (n = 10), the correlation was less strong (r = 0.6 to 0.7). Methionine showed a strong positive correlation in pulmonary samples (r = 0.93), and negative correlation in great veing samples (r = -0.68). Lactic acid showed a strong negative correlation in pulmonary samples (r = -0.93) but a positive correlation in great vein samples (r = 0.71). Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, and bilirubin had a weak positive correlation with drug levels in great vein samples but not pulmonary samples. The results suggest that hepatic enzymes are relatively poor markers for postmortem hepatic drug shifts but that amino acids, particularly methionine, may be useful markers for pulmonary drug shifts.
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PMID:Possible markers for postmortem drug redistribution. 898 78

Intrahepatic cholestasis of pregnancy (ICP) is a syndrome usually manifesting during the third trimester of pregnancy and disappearing after delivery. Multiple factors seem to be involved in pathogenesis of the syndrome; however, ICP appears to take place in women congenitally hypersensitive to estrogens. Typical is pruritus, which may be followed by jaundice and associated with other less common symptoms. The biochemical parameters are characteristically altered: an increase in the levels of aminotransferases (AST, ALT), total bile acids and alkaline phosphatase is observed; while serum GGT are normal. Maternal prognosis is benign. By contrast, a higher risk of acute fetal distress and prematurity has been reported. Various drugs are used in the treatment of ICP. We present the case of a patient treated with S-adenosyl-L-methionine (SaMe). SaMe therapy has proved to be effective in improving the altered biochemical parameters, whose normalization was obtained before delivery.
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PMID:[Intrahepatic cholestasis in pregnancy]. 911 20


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