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)

Thirteen biochemical parameters (viz. glucose, calcium, inorganic phosphorous, urea nitrogen, uric acid, cholesterol, albumin, total protein, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) were determined in serum and partly in liver of rats 1-28 days after i.p. aflatoxin B1 (AFB) (3 mg/kg). Histological examinations of the liver were also made in parallel to the biochemical studies. In the serum, enzyme activities and total bilirubin level increased and peaked on the 2nd day, while other activities of aspartate aminotransferase and alanine aminotransferase in the liver significantly decreased and reached a minimum on the 2nd day after AFB administration. The depression of the liver enzyme activities persisted over 7 days. The liver protein content also reduced transiently during 1-1.5 days. However, all biochemical parameters returned to normal levels 2 weeks after treatment, and remained so throughout the rest of experimental period. Histological changes in the liver were very similar to those reported by other.
Br J Cancer 1980 Aug
PMID:Sequential biochemical and histological changes in rats treated with aflatoxin B1. 742 38

(AxT6)F1 hybrid mice received s.c. transplants from (AxT6)F1 mammary carcinomas. At 1, 2 or 4 weeks after tumour transplantation, the mice were bled to obtain plasma and then challenged with 25 micron E. coli lipopolysaccharide (LPS) endotoxin i.v. The mice were killed 24 hr later, further plasma was obtained and their liver ratios and spleen ratios were determined. A similar procedure was carried out on non-tumour-bearing mice. Progressive tumour growth was associated with an increase in the liver ratio. In parallel, mice with 4-week tumour transplant showed increased uptake of colloidal carbon particles and 51Cr-labelled sheep red blood cells in the liver. The plasma amino aspartate transaminase (AST) and the ornithine carbamoyl transferase (OCT) showed a constant rise in all groups of mice after LPS injection. However, at 24 hr after LPS injection, the AST level showed the greatest rise in mice with 4-week tumour transplants. By contrast, OCT, which is liberated only from hepatocytes, showed the greatest rise in non-tumour-bearing mice.
Br J Cancer 1980 Dec
PMID:Hyperphagocytosis and the effect of lipopolysaccharide injection in tumour-bearing mice. 745 24

Pseudoisocytidine (psi ICyd) is a C-nucleoside with enhanced stability and resistance to enzymatic deamination when compared to 5-azacytidine and 1-beta-D-arabinofuranosylcytosine. Elimination kinetics in plasma using [14C]psi ICyd showed a beta-phase for t1/2 for 14C of 2 hr and a beta-phase t1/2 of unchanged psi ICyd of 1.5 hr. Net recovery of radioactivity in urine over 24 hr varied between 40 and 80% of the administered dose; 50 to 90% was unchanged drug and the rest was pseudouridine. Human leukemic cells in vitro deaminated psi ICyd very slowly, formed appreciable quantities of pseudoisocytidine triphosphate, and incorporated small amounts into RNA and DNA. Clinical trials were done using a daily i.v. injection for 5 consecutive days. Hematological or intestine toxicities were not seen, nor was depression of white blood cell count observed in leukemic patients. Hepatic toxicity proved to be dose limiting; this was characterized by an early phase with elevation of prothrombin time and aspartate aminotransferase. A later phase with cirrhosis was observed in two patients. Autopsy showed massive hepatic necrosis in patients dying of acute toxicity and micronodular cirrhosis in one patient dying with the chronic form.
Cancer Res 1980 Nov
PMID:Biochemical, pharmacological, and phase I clinical evaluation of pseudoisocytidine. 747 Oct 64

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.
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PMID:Frozen section evaluation of donor livers before transplantation. 750 53

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), alpha 1-antitrypsin (ATT), alpha 1-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.
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PMID:Interleukin-6 and acute-phase proteins in head and neck cancer. 754 87

We studied the variability in doxorubicin pharmacokinetics in 27 patients, all of whom had normal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatase, albumin, creatinine) and physical characteristics (age, gender, height, weight, tumour type) was investigated. The 6 men had a significantly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh-1 m-2, respectively; P = 0.002). Doxorubicin clearance was significantly lower in patients with breast cancer than in those with other tumours (median values, 26 and 53 lh-1 m-2, respectively; P = 0.0008). The other biochemical and physical parameters did not correlate with doxorubicin clearance. However, in multivariate analysis, gender was the only factor predicting doxorubicin clearance (r2 = 40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) was higher in the men than in the women (median values, 0.62 and 0.36, respectively; P = 0.03). We conclude that gender may be an important determinant of doxorubicin clearance in patients with normal liver biochemistry.
Cancer Chemother Pharmacol 1995
PMID:Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry. 755 38

An analogue of Hoechst 33258, bearing a phenolic hydroxyl group in the meta rather than para position, was designed using molecular graphics to introduce hydrogen-bonding potentials between this OH group and the C = O group of cytosine-9 and the NH2 group of guanine-4', of the opposite strand of the B-DNA duplex, d(CGCGAATTCGCG)2. This derivative (meta-Hoechst) was synthesized in seven steps and characterized. Its binding to DNA was assessed by measurements of melting temperatures (Tm) and found to be similar in strength and AT preference to the parent Hoechst 33258 at this gross level. The AT preference of meta-Hoechst and Hoechst 33258 was probed further using hydroxyl radical footprinting on the tyrT DNA fragment, for which clear footprints were detected at AAT, AAA and ATAT runs, as for netropsin and distamycin. Hydroxyl radical footprinting was carried out on a trimer of CGCGAATTCGCG cloned into a longer DNA fragment, for which clear footprints for both Hoechst 33258 and meta-Hoechst were detected in regions with four or more contiguous AT base pairs. Three cell lines derived from haematological malignancies were more sensitive to both Hoechst 33258 and meta Hoechst than lines derived from solid tumours, but there was no significant difference between the activity of these two Hoechst derivatives.
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PMID:Synthesis, DNA binding, footprinting and in vitro antitumour studies of a meta-hydroxy analogue of Hoechst 33258. 757 88

The medical and necropsy records of 41 cats diagnosed with nonlymphomatous hepatobiliary (NLHB) masses, including neoplasia and cysts, were reviewed. Overall, benign masses (n = 27) were more common than malignant ones (n = 14). The single most common malignancy was cholangiocellular carcinoma. The median age at diagnosis was significantly lower (P < .01) for cats with malignant rather than benign disease. Clinical signs associated with hepatobiliary neoplasia were usually vague and included lethargy, vomiting, and anorexia, often present for at least 2 weeks before presentation. Benign masses were an incidental finding in significantly more (P < .01) of the cases than were malignant masses. Median values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin were significantly higher (P < .05) in cats with malignant versus benign masses. The prognosis for malignant disease was poor, with 86% of the cats dying or being euthanatized during hospitalization. Cats with benign disease that underwent exploratory celiotomy were more likely to recover and warranted a more favorable prognosis than cats with malignant tumors. Factors associated with malignancy included age at presentation, presence of clinical signs at presentation, and specific serum chemistry changes.
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PMID:Nonlymphomatous hepatobiliary masses in cats: 41 cases (1972 to 1991). 783 94

The rodent liver carcinogen and hepatic peroxisome proliferator methylclofenapate (MCP) has been evaluated for genetic toxicity in a range of in vitro and rodent genotoxicity assays. It gave a negative response in each of the following assays: mutagenicity to S. typhimurium and E. coli (+/- S9 mix, plate and pre-incubation assays), clastogenicity to cultured human lymphocytes and CHO cells (+/- S9 mix), a mouse bone marrow micronucleus assay (24h and 48h sampling), a rat liver assay for UDS in vivo (12h sampling), assays for lac I (Big Blue) and lac Z (Muta Mouse) mutations in the liver of transgenic mice, and an assay of the ability of MCP to modify the mutagenicity to the liver of dimethylnitrosamine in both transgenic mutation assays. The micronucleus and UDS assays were conducted using a single administration of MCP at its maximum tolerated dose, while the transgenic assays were conducted using nine daily administrations of MCP at its cancer bioassay dose level. These nine daily administrations were shown to double the weight of the liver of non-transgenic, Big Blue and Muta Mice, as well as leading to a dramatic proliferation of peroxisomes (electron microscopy) in the livers of each strain. These changed parameters had returned to control levels when the mutation analyses were conducted (10 days after the final dose of MCP). Despite the liver enlargement observed following MCP administration, no evidence of mitotic activity was observed in treated livers, although an increased number of cells were undergoing replicative DNA synthesis during the final 3 days of the 9 days of administration (BUdR assessment of S-phase). Liver biochemistry parameters (ALT, AST, AP, CK, GGT and albumin) were unaffected by the chronic (9 day) administration of MCP indicating an absence of hepatic toxicity. These combined observations favour a non-genotoxic mechanism of action for the hepatic carcinogenicity of MCP. The clastogenicity in vitro of the perixisome proliferator Wyeth 14,643 has been confirmed in CHO cells, but it is noted that this chemical is more soluble than is MCP. In particular, at the highest dose level at which MCP could be tested, Wy 14,643 was also non-clastogenic.
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PMID:Evaluation of the genetic toxicity of the peroxisome proliferator and carcinogen methyl clofenapate, including assays using Muta Mouse and Big Blue transgenic mice. 785 96

Hepatic and renal subacute toxicity induced by the antineoplastic drugs chlorambucil, cisplatin, epirubicin and methotrexate and the steroid alkylating agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13, 17-lactam (p-[bis(2-chloroethyl) amino] phenyl) acetate was investigated in rats using serum biochemical parameters. Toxicological evaluation was performed in serum samples following the administration of dose regimens of the agents that were previously shown to be effective in suppressing malignant tumor growth or to prolong survival in tumor bearing animals. Hepatic and renal subacute toxicity was evaluated by measuring enzyme activity or concentrations of: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total cholesterol, gamma-glutamyltransferase, glucose, potassium, sodium, blood urea nitrogen and uric acid. The use of the above serum biochemical parameters indicated that the overall toxicity impact of the antitumor drugs was methotrexate < cisplatin < epirubicin < chlorambucil. The homo-azasteroid ester only transiently affected the biochemical parameters associated with renal toxicity, while it affected some of the biochemical parameters associated with hepatic toxicity, though to a significantly lower extent than the antitumor drugs.
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PMID:Evaluation of kidney and liver subacute toxicity of antitumor agents using serum biochemical parameters in rats. 790 82


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