Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
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Serum electrolytes, metabolites and enzymes were determined in arterial blood of chronically cannulated dogs at room temperature and on exposure to 44-50 degrees C. These dogs were naturally acclimated to hot, arid conditions. In dogs maintaining their rectal temperatures (TR) below 40 degrees C, no significant changes were seen in the levels of Na+, Cl-, cholesterol, uric acid, alkaline phosphatase, lactic dehydrogenase or glutamic-pyruvic transaminase (SGPT). K+, CO2, glucose decreased significantly, and urea nitrogen (BUN) and glutamic-oxaloacetic transaminase (SGOT) showed small but significant increases. In several cases of excitable dogs, in which TR increased above 40 degrees C, we found large, significant increases in uric acid, SGPT and SGOT, and a decrease in cholesterol. The results suggest that in dogs maintaining their TR when exposed to high temperatures, changes in serum constituents indicate merely the presence of respiratory alkalosis and an increased energetic demand. When control of TR is lost, changes occur which suggest liver, and possibly cardiac, tissue damage.
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PMID:Physiological responses of dogs on exposure to hot, arid conditions. Serum constituents. 56 59

1. The prairie dog has been used extensively for the study of gallstone genesis and gallstone dissolution therapies, and has recently been implicated in an effort to prevent total parenteral nutrition-associated cholelithiasis with intravenous chenodeoxycholate. 2. Towards this effort, it is important that a range of normal blood chemistry values be reported for the prairie dog. This paper reports the mean values for a complete blood cell count, electrolytes, blood urea nitrogen, creatinine, calcium, phosphorus, liver enzymes, total bilirubin, protein, albumin, cholesterol, triglycerides and lipids for 45 adult prairie dogs. 3. The prairie dog has normochromic, microcytic blood with an increased number of red blood cells. The prairie dog also has a high concentration of small platelets. 4. The prairie dog has a higher CO2 concentration with a slightly increased potassium concentration than is found in man. The anion gap is 12 with a calculated serum osmolality of 316. The BUN concentration is elevated with a 3-fold increase in the AST concentration. 5. The prairie dog has lower serum values for cholesterol, VLDL and LDL cholesterol than man. In the prairie dog, HDL cholesterol consists of 67% of the total cholesterol concentration and the LDL and HDL ratio is 0.3.
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PMID:Hematologic and blood chemistry data for the prairie dog (Cynomys ludovicianus). 135 55

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In genetically susceptible pigs, MH can be induced by volatile, halogenated anaesthetics such as halothane. Within a series of pharmacological investigations, a fulminant MH could be induced in 59 of 66 homozygous halothane-susceptible pigs by a challenge with 3% halothane for 15 minutes. The typical MH was characterized by sudden appearance of tachycardia, muscle rigidity with typical extension of the hindlimbs, increase of body temperature, acidosis-caused by rapid increase of CO2 and lactate production-, hyperkalaemia and increased activity of creatine kinase (CK) and aspartate transaminase (AST). In seven homozygous MH-susceptible pigs, this typical MH could not be induced by halothane. These animals responded with sudden appearance of bradyarrhythmia and decrease of arterial pressure. In these MH-atypical pigs (MHA) neither the typical extension of hindlimbs nor a hyperthermia occurred. Compared to a group of 6 MH-susceptible pigs with typical reactions to halothane (MHS), the biochemical alterations were significantly retarded in MHA-pigs. These atypical reactions to halothane could be the effect of decreased cardiac output. Concerning the atypical reactions, we observed a familiar predisposition in MH-susceptible pigs. Although atypical reactions were not found in a group of homozygous halothane-nonsusceptible pigs (MHN), a possible explanation for atypical reactions could be a MH-independent halothane-susceptibility of the myocardium+ in MHA-pigs. On the other side the data may indicate that a primary defect in both the skeletal muscle and also the myocardium is involved in MH. The different reactions to halothane in MH-susceptible pigs could point to a genetic heterogeneity.
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PMID:Atypical reactions to halothane in a subgroup of homozygous malignant hyperthermia(MH)-susceptible pigs: indication of a heterogenous genetic basis for the porcine syndrome. 142 16

From a database of 93,077 in-patient admissions, patients assigned to catastrophic, very severe, moderately severe, and average 30-day mortality risk categories (as defined in Medicare Hospital Mortality Information, 1989 release, from the Health Care Financing Administration (HCFA] were selected for study. These admissions account for 30% of all admissions, but 70% of all deaths up to 1 year post admission. To determine whether laboratory information adds to the predictive power of the information used by HCFA, we compare the performance of 1 year survival predictors (Cox model) that use only diagnostic, demographic, and comorbidity information, with the performance of predictors that also include laboratory information. Using a separate set of patients not used for model definition, we find that laboratory data contain significant prognostic information independent of that already available in non-laboratory data. In HCFA's catastrophic disorders for example, non-laboratory information reduces the average risk of predicting a wrong outcome by 17% relative to considering only catastrophic group membership, and adding laboratory data reduces this risk by a further 21%. These improvements result primarily from considering the outcomes of a small set of routine laboratory tests (maximum BUN, AST, and WBC, and minimum CO2, hematocrit, and sodium).
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PMID:Laboratory data predicts survival post hospitalization. 175 70

In the following study, normal blood values were performed on 58 Friesian calves (30 males and 28 females) under preexisting Moroccan management conditions. The following parameters were evaluated: pH-value, p.CO2, actual HCO3, BE, BB, RBC, WBC, PCV, Hb, MCV, MCHC, Glucose, lactate, urea, creatinine, total protein, total bilirubin, enzyme activities of AST and GGT and electrolyte-values (Na, K, Cl). The values of all parameters varied significantly with age with the exception of MCV, MCHC and K. The female calves presented higher values of act. HCO3, BE, BB, Hb, PCV and MCV than the male calves (p less than 0.01). The calves were born in mixed acidosis stage which was largely restored 24 hours later. At the weaning, the calves showed a slight metabolic acidosis with a partial respiratory compensation. The metabolic acidosis was accompanied with an increase of lactate level in blood plasma. During the first month of life, the development of an anaemia (PCV decreased) was observed. The mean values of glucose and total protein increased after colostrum intake, whereas the electrolyte values in blood plasma decreased. In general, the mean values of lactate, creatinine, urea, total bilirubin and the activities of AST and GGT decreased with age, while glucose and total protein remained nearly unchanged. The age and the sex should be taken in consideration judging the above mentioned parameters in a new born calf from birth to weaning (here: two months).
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PMID:[Hemocytological and hemobiochemical studies in black pied, clinically healthy breeding calves in Morocco]. 204 72

Quality-control (QC) procedures (i.e., decision rules used, numbers of control measurements collected per run) have been selected for individual tests of a multitest analyzer, to see that clinical or "medical usefulness" requirements for quality are met. The approach for designing appropriate QC procedures includes the following steps: (a) defining requirements for quality in the form of the "total allowable analytical error" for each test, (b) determining the imprecision of each measurement procedure, (c) calculating the medically important systematic and random errors for each test, and (d) assessing the probabilities for error detection and false rejection for candidate control procedures. In applying this approach to the Hitachi 737 analyzer, a design objective of 90% (or greater) detection of systematic errors was met for most tests (sodium, potassium, glucose, urea nitrogen, creatinine, phosphorus, uric acid, cholesterol, total protein, total bilirubin, gamma-glutamyltransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase) by use of 3.5s control limits with two control measurements per run (N). For the remaining tests (albumin, chloride, total CO2, calcium), requirements for QC procedures were more stringent, and 2.5s limits (with N = 2) were selected.
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PMID:Selection of medically useful quality-control procedures for individual tests done in a multitest analytical system. 230 66

In an open, exploratory study, the safety of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC) was investigated. Seven patients in stages I to III and two patients in stage IV were treated for 1 year with 1 g/day of UDCA. Clinical symptoms, and alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase (GOT) and aspartate aminotransferase (GTP) levels improved significantly within three months and remained at the lower levels for the period of observation. Results of the galactose elimination capacity (4.7 +/- S.D. 1.4 mg/min per kg) and the aminopyrine breath test (0.60 +/- 0.33% dose/kg per mmol CO2) remained unchanged for 1 year. In all patients total serum bile acids increased and quantitatively UDCA became the most important bile acid. In patients in stages I to III this increase, however, was modest, whereas in patients in stage IV, total serum bile acids reached levels of 140 and 157 mumol/l and UDCA, levels of 90 and 103 mumol/l, respectively. It is concluded that UDCA appears to be safe only in stages I to III and that prognostic stratification based on bile acid levels or on the histological stage of the disease should be an important aspect of controlled clinical trials.
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PMID:Ursodeoxycholic acid in primary biliary cirrhosis: no evidence for toxicity in the stages I to III. 236 81

Pathways of glutamine metabolism in resting and proliferating rat thymocytes and established human T- and B-lymphoblastoid cell lines were evaluated by in vitro incubations of freshly prepared or cultured cells for one to two hours with [U14C]glutamine. Complete recovery of glutamine carbons utilized in products allowed quantification of the pathways of glutamine metabolism under the experimental conditions. Partial oxidation of glutamine via 2-oxoglutarate in a truncated citric acid cycle to CO2 and oxaloacetate, which then was converted to aspartate, accounted for 76% and 69%, respectively, of the glutamine metabolized beyond the stage of glutamate by resting and proliferating thymocytes. Similar results were obtained with the lymphoblastoid T- and B-cell lines. Complete oxidation to CO2 in the citric acid cycle via 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase accounted for only 25% and 7%, respectively. In proliferating cells a substantial amount of glutamine carbons was also recovered in pyruvate, alanine, and especially lactate. The main route of glutamine and glutamate entrance into the citric acid cycle via 2-oxoglutarate in lymphocytes appears to be transamination by aspartate aminotransferase rather than oxidative deamination by glutamate dehydrogenase. In the presence of glucose as a second substrate, glutamine utilization and aspartate formation markedly decreased, but complete oxidation of glutamine carbons to CO2 increased to 37% and 23%, respectively, in resting and proliferating cells. The dipeptide, glycyl-L-glutamine, which is more stable than free glutamine, can substitute for glutamine in thymocyte cultures at higher concentrations.
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PMID:Metabolism of glutamine in lymphocytes. 256 63

Energy metabolism in proliferating cultured rat thymocytes was compared with that of freshly prepared non-proliferating resting cells. Cultured rat thymocytes enter a proliferative cycle after stimulation by concanavalin A and Lymphocult T (interleukin-2), with maximal rates of DNA synthesis at 60 h. Compared with incubated resting thymocytes, glucose metabolism by incubated proliferating thymocytes was 53-fold increased; 90% of the amount of glucose utilized was converted into lactate, whereas resting cells metabolized only 56% to lactate. However, the latter oxidized 27% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Activities of hexokinase, 6-phosphofructokinase, pyruvate kinase and aldolase in proliferating thymocytes were increased 12-, 17-, 30- and 24-fold respectively, whereas the rate of pyruvate oxidation was enhanced only 3-fold. The relatively low capacity of pyruvate degradation in proliferating thymocytes might be the reason for almost complete conversion of glucose into lactate by these cells. Glutamine utilization by rat thymocytes was 8-fold increased during proliferation. The major end products of glutamine metabolism are glutamate, aspartate, CO2 and ammonia. A complete recovery of glutamine carbon and nitrogen in the products was obtained. The amount of glutamate formed by phosphate-dependent glutaminase which entered the citric acid cycle was enhanced 5-fold in the proliferating cells: 76% was converted into 2-oxoglutarate by aspartate aminotransferase, present in high activity, and the remaining 24% by glutamate dehydrogenase. With resting cells the same percentages were obtained (75 and 25). Maximal activities of glutaminase, glutamate dehydrogenase and aspartate aminotransferase were increased 3-, 12- and 6-fold respectively in proliferating cells; 32% of the glutamate metabolized in the citric acid cycle was recovered in CO2 and 61% in aspartate. In resting cells this proportion was 41% and 59% and in mitogen-stimulated cells 39% and 65% respectively. Addition of glucose (4 mM) or malate (2 mM) strongly decreased the rates of glutamine utilization and glutamate conversion into 2-oxoglutarate by proliferating thymocytes and also affected the pathways of further glutamate metabolism. Addition of 2 mM-pyruvate did not alter the rate of glutamine utilization by proliferating thymocytes, but decreased the rate of metabolism beyond the stage of glutamate significantly. Formation of acetyl-CoA in the presence of pyruvate might explain the relatively enhanced oxidation of glutamate to CO2 (56%) by proliferating thymocytes.
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PMID:Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism. 286 9

The isolated perfused rat kidney was shown to synthesize serine from aspartate or glutamate, both of which are also precursors of glucose. The major products of aspartate metabolism were ammonia, serine, glutamate, glucose, glutamine and CO2. Perfusion of kidneys with aspartate in the presence of amino-oxyacetate resulted in a near-complete inhibition of aspartate metabolism, illustrating the essential role of aspartate aminotransferase in the metabolism of this substrate. Radioactivity from 14C-labelled aspartate and from 14C-labelled glycerol was incorporated into serine and glucose. Production of both glucose and serine from aspartate was suppressed in the presence of 3-mercaptopicolinic acid. These data provide evidence for the operation of the phosphorylated and/or non-phosphorylated pathway for serine production to the presence of 3-mercaptopicolinic acid. This is explained by simultaneous glycolysis. The rate of glucose production, but not that of serine, was greater in kidneys perfused with glutamate or with aspartate plus glycerol than the rates obtained by perfusion with aspartate alone. These data are taken to suggest that serine synthesis occurred at a near-maximal rate, and that the capacity of the kidney for serine synthesis from glucose precursors is lower than that for glucose synthesis.
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PMID:Serine synthesis by an isolated perfused rat kidney preparation. 286 20


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