Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute necrosis of R3230AC mammary tumor or thyroid carcinoma subcutaneously implanted in F344 rats was achieved by injection of a strongly hypertonic hexose and serotonin solution at 37 degrees C into and around the tumors. Changes in gross metabolism, hematology, and blood chemistry were then followed over a 9-day period, and they were most marked during or at the end of the first 24 hours. Food intake of the rats was sharply reduced, whereas drinking and diuresis were increased. Marked hemodilution and increased serum concentrations of aspartate aminotransferase, potassium, and uric acid were observed, as well as stable serum concentrations of sodium and chloride. Glucose overload, as opposed to fructose overload, led to secondary hypoglycemia. From day 2 food consumption returned to normal and increased thereafter. Water intake and urine output remained high. After an initial loss, body weight caught up with that of control rats. Hematocrit recovered partially, whereas blood chemistry progressively returned to about normal values.
J Natl Cancer Inst 1983 May
PMID:Systemic tolerance of osmotically induced oncolysis in rats. 657 33

Clone A human colon adenocarcinoma cells were grown in three-dimensional artificial capillary culture (ACC) to determine responses of capillaries treated 3 weeks after tumor cell inoculation with a specific, easily quantifiable cytotoxic agent, ionizing radiation. The high-density growth of tumor cells in ACC can be considered to be an in vitro analogue of a solid tumor. Changes in extracapillary space (ECS) fluid concentrations of lactate dehydrogenase (LDH) and aspartate aminotransferase (GOT) and the utilization of glucose in circulating medium were monitored after a supralethal radiation dose (90 Gy) of X-rays. Immediately after irradiation, increased levels of LDH and GOT were found that reached maximum levels about four to five times those found in nonirradiated control capillaries at 10-13 days post irradiation and then declined. Patterns of enzyme production appeared to correlate with the numbers of nonviable tumor cells collected from the ECS of the artificial capillaries. In contrast, glucose utilization showed little correlation with either enzyme concentration or dead cell production. It was determined that, while capillaries grown and treated in this manner appear to respond in a dose-dependent manner to ionizing radiation (as indicated by changes in LDH and GOT levels), these particular end points are relatively insensitive and are not suitable for studies in which therapeutic levels of X-radiation might be given. In other studies, tumor cells were removed from unirradiated capillaries by trypsinization and used to obtain complete survival curves after graded doses of X-radiation. The dose-response curves obtained indicate that clone A colon tumor cells grown in ACC show a marked decrease in their ability to accumulate sublethal radiation injury as compared to responses of these cells growing exponentially in asynchronous monolayer cultures, to synchronized mid-G1 tumor cells, or to tumor cells in stationary growth phase. These data suggest that ACC is a potentially useful model to study the effects of cytotoxic agents on human tumor cells.
J Natl Cancer Inst 1984 Jun
PMID:X-ray responses of human colon tumor cells grown in artificial capillary culture. 658 47

The whole-body protein synthesis rate (PSR) was measured in 5 control patients (group I) and 38 patients in various clinical states (group II). A single pulse of [15N]glycine was given and the PSR calculated from the 15N enrichment in the urinary ammonia excreted over the next 10 hr. The patients' results fell into three separate groups: group IIa patients were nonstressed and had uneventful recoveries (3.1 +/- 0.6 g prot./kg/day), their PSRs were the same as the control group I, (3.1 +/- 1.0 g prot./kg/day); group IIb patients were stressed, had higher PSRs (6.3 +/- 0.9 g prot./kg/day), one of whom died, and the rest had more complications than group IIa; group IIc patients had very high PSRs (15.4 +/- 6.1 g prot./kg/day), all of whom were seriously ill, and 8 out 12 died; Data are +/- 1 SD. The PSR correlated with the serum glutamate oxaloacetate transferase (SGOT, P less than 0.01). We concluded: (i) [15N]glycine cannot be used to measure the PSR in patients with evidence of liver disease; the results are best interpreted in terms of glycine metabolism; (ii) the "apparent" PSR correlated with clinical status; and (iii) an elevated PSR in a patient with a malignancy is not necessarily due to protein metabolism by the tumor.
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PMID:Whole-body protein turnover in metabolically stressed patients and patients with cancer as measured with [15N] glycine. 662 86

In 143 patients undergoing 199 cycles of total parenteral nutrition (TPN), alkaline phosphatase (AP), serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), direct bilirubin (DB), total bilirubin (TB), and lactic dehydrogenase (LDH) were measured and recorded before initiating TPN and weekly for seven weeks or until TPN was discontinued. Patterns of change were elevations and then plateaued. Direct bilirubin, TB and LDH showed no significant change. The patterns were independent of patient age, amount of fat emulsion administered, tumor burden, and nonprotein calorie to basal energy expenditure ratio.
Cancer 1982 Mar 15
PMID:The impact of total parenteral nutrition on liver function tests in patients with cancer. 680 Jun 31

The influence of intestinal microflora on the hepatotoxic effects of dimethylnitrosamine (DMN) or dimethylamine (DMA) plus NaNO2 was studied by comparing the degree of liver necrosis and the levels of serum alanine aminotransferase (GPT) and aspartate aminotransferase (GOT) in germ-free and conventional male Wistar rats (320 to 340 g). In one experiment, both germ-free and conventional rats were intubated with DMN in respective doses of 8, 9, and 10 mg/kg of body weight, while in another experiment, both groups were intubated with DMA (1500 mg/kg) plus NaNO2 (100 mg/kg). In both experiments, 48 hr after intubation, there was a marked difference in the degree of liver necrosis and the levels of serum GPT and GOT between the groups. In particular, a dose of 8 mg of DMN or 1500 mg of DMA plus 100 mg of NaNO2 produced severe liver necrosis in the majority of germ-free rats, while the same dose did not produce any detectable liver necrosis in the majority of conventional rats. At a dose of 8 mg, serum GPT and GOT levels were raised to 22 and 15 times normal values, respectively, in germ-free rats, but only to about twice the normal values for both levels in conventional rats. At the combination dose of DMA plus NaNO2, the levels of serum GPT and GOT were raised to 40 and 30 times normal values, respectively, in germ-free rats, while both levels remained almost normal in conventional rats. Thus, the results indicated that the liver of the germ-free state was far more susceptible to the acute toxic effects of DMN as well as DMA plus NaNO2 administration at a certain dose range than was the liver of the conventional state, suggesting the influence of the absence of microflora.
Cancer Res 1983 Jun
PMID:Susceptibility of germ-free rats to the hepatotoxic effects of dimethylnitrosamine or dimethylamine plus sodium nitrite administered orally. 685 Jun 4

As a model to study the possible early side effects of cultured T-cells (CTC) as a potential for adoptive cellular immunotherapy of human tumors, chimpanzees received iv infusions of 10(9) autologous, mixed lymphocyte culture-primed CTC. Complete blood counts, urinalyses, chest X-rays, blood chemistries, and serum immunoelectrophoresis were normal, and serologic studies were negative throughout the 3 weeks of observation. Serial transaminase levels were followed in 2 chimps, and mild increases in serum glutamic-oxaloacetic transaminase were seen in both and serum glutamic-pyruvic transaminase in 1 at 24 hours following each CTC infusion, but the levels returned to normal within 7 days. A liver biopsy specimen was normal. Fluorescence-activated cell sorter analysis of cells incubated with day 28 serum revealed weak labeling of only phytohemagglutinin (PHA)-stimulated lymphoblasts and of CTC, suggesting that a weak anti-PHA antibody was generated. These studies indicate that infusions of autologous, in vitro-primed CTC are accompanied by little clinical toxicity in the chimp model but that they may be weakly immunogenic.
J Natl Cancer Inst 1981 Aug
PMID:Clinical effects of infusions into chimpanzees of primed autologous cultured T-cells. 697 57

The Authors have tested serum levels of CEA, ferritin, Alpha-1-antitrypsin, parathyroid hormone (PTH) and calcitonin (CT) in 286 patients affected by lung, gastrointestinal, breast and other kinds of cancer and by non neoplastic diseases. 50 healthy subjects were tested as matched controls too. None of the tested patients was subjected to blood transfusion, therapy with iron, radio- or chemotherapy before the blood drawing. Cea, ferritin, PTH and CT were tested by radioimmunoassay; AAT by laser nephelometry. All the healthy subjects showed serum levels of the markers in the normal ranges. Also the percent of cases with contemporaneous pathological markers was examined. The obtained data have been statistically controlled with "chi square" test. The results show that CEA, ferritin, AAT and CT are higher in the tumor groups than in the others. On the contrary PTH seems to be not useful as tumor marker. The Authors conclude affirming that it is not possible to use any of the tested substances as a specific tumor marker but it is useful to test at the same time these markers in the patients suspected to be affected by cancer for an early diagnosis and therapy, as there are few false positive and false negative cases.
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PMID:[Association of serum tumor markers in solid neoplasms (CEA, ferritin, alpha 1-antitrypsin, parathormone and calcitonin)]. 698 16

Patient characteristics of 272 patients entered in a clinical trial conducted by the Pediatric Intergroup Ewing's Sarcoma Committee between June 1972 and November 1978 were examined for their relationship to prognosis. Prognosis was defined as disease-free survival time (time to local recurrence and/or metastatic disease) and overall survival time; all times were measured from the start of treatment. In a multivariate regression model, primary site of disease was the major variable that influenced prognosis, and patients with pelvic sites had the least favorable prognoses, followed by those with proximal and rib sites. The most favorable sites were distal and other. The median disease-free and survival times in weeks by primary site were, respectively: pelvis (69, 112), proximal (102, 141), rib (105, 109+), distal (226+, 240), and other (96+, 199+). Females had better prognoses than males; the median survival times were 197 and 147 weeks, respectively. An abnormal liver function as indicated by an abnormal serum glutamic-oxaloacetic transaminase value (greater than 45 IU) was a bad prognostic sign, although only 8 patients had this finding; their median survival time was 94 weeks. Patients who had resections had a slight advantage in survival compared with those having biopsies, though the difference favoring resection patients was not consistent for both sexes in any primary site. Individual characteristics of the patients that were of prognostic significance were: blood lymphocyte counts (high counts favorable), polymorphonuclear leukocyte counts (high counts unfavorable), and time from symptoms to diagnosis (times less than 1 mol favorable). Patients who received treatment 2 had significantly poorer prognoses than those given treatments 1 or 3. The median disease-free and survival times by treatment were (in wk): 1 (134, 198+), 2 (81, 120), and 3 (123, 182).
Natl Cancer Inst Monogr 1981 Apr
PMID:Prognostic factors in children with Ewing's sarcoma. 702 95

We found heterogenous ornithine oxoacid aminotransferase (L-ornithine: 2-oxo-acid aminotransferase, EC 2.6.1.1.3) in rat ascites hepatoma AH 130 cells. Compared with enzymes from normal rat tissues, this heterogenous enzyme showed larger Km values for 2-oxoglutarate, a different elution-profile upon affinity chromatography with 2-oxoglutarate, more anionic mobility upon polyacrylamide gell electrophoresis, and a clearly different salting-out property upon ammonium sulfate fractionation. Similar heterogeneity of this aminotransferase was found in human cancer cells.
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PMID:Ornithine oxoacid aminotransferase found in AH 130 ascites hepatoma cells. 705 19

The increasing concern of industrialized societies over the potential health hazard of synthetic chemicals in the occupational environment has led to government requirements for medical laboratory screening of workers. The specific tests for such screening programs are most often selected on the basis of medical experience which utilized them in symptomatic or hospitalized populations. Required screening tests for hepatic injury including cancer in vinyl chloride workers has been systematically and prospectively studied in an industrial population working with synthetic rubber and plastics. Approximately 1300 employees were studied over a five-year period. A cohort of 969 male employees, for the purposes of analysis, were divided into a "standard" and "nonstandard" population based upon the absence or presence of significant medical disease (including liver disease). A subcohort of 120 individuals was further identified based on availabiliity of liver biopsy. Evaluation of federally required studies included alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP), alanine aminotranserase (ALT, SGPT), aspartic aminotransferase (AST, SGOT) and bilirubin (BR). Also studied were indocyanine green clearance (ICG) and radioisotopic liver spleen scans (L-S scans). The GGTP provided the highest positive predicted value as a screening test for identifying "nonstandard" individuals (individuals with all types of medical disease) followed by ICG, AST, ALT, L-S scan, AP, and BR. In the identification of asymptomatic liver disease the GGTP had the least specificity due to a high false positive rate, while the AP provided the highest specificity. The ICG clearance however, provided the best combination of positive predictive value and sum of specificity and sensitivity. The AP provided additional increase in specificity as a follow-up study. There was no evidence that any of the other federally required tests added any additional benefit and did add significant increase in the false positive rate. These studies support the need for evaluating screening tests as to their sensitivity, specificity and positive predictive value, in asymptomatic individuals, before they are made established requirements.
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PMID:Effectiveness of federally required medical laboratory screening in the detection of chemical liver injury. 733 29


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