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)

Forty-seven male Macaca mulatta, 3 to 4 kg weight, were inoculated intravenously or subcutaneously with various doses of yolk sac-grown Rickettsia rickettsii. Thirty-four macaques became febrile and exhibited signs of infection ranging from transient illness with a few days of fever to severe illness with subsequent death. The rash appeared more frequently in the macaques inoculated subcutaneously. Febrile macaques that survived had leukocytosis, with concomitant neutrophilia. Febrile macaques that died had, in addition, marked terminal leukopenia and thrombocytopenia. Packed cell volume of all febrile macaques decreased. In almost all of the febrile macaques, there were increased serum urea nitrogen, glutamic-oxaloacetic transaminase, and lactate dehydrogenase and decreased total serum protein and amylase concentrations. A few febrile macaques had increased bilirubin values and decreased sodium, chloride, phosphorus, and alkaline phosphatase concentrations. Changes did not occur in serum glucose, potassium, calcium, and glutamic-pyruvic transaminase values. The experimental form of Rocky Mountain spotted fever in the macaque provides a subhuman primate model for studying the pathophysiology of this disease.
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PMID:Changes in blood serum constituents and hematologic values in Macaca mulatta with Rocky Mountain spotted fever. 82 Feb 24

The effects of intravenous administration of Escherichia coli endotoxin were studied in eight mature lactating cows. Three cows were studied following intrammary infection with E. coli. Significant clinical findings are presented. Significant clinico-pathological findings include leukopenia, decreased blood serum calcium concentrations and increased levels of serum glutamic-oxaloacetic transaminase and serum ornithine-carbamyl transferase. Significant elevations of plasma corticosteroids were also noted.
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PMID:Clinical and clinico-pathological effects of Escherichia coli endotoxin in mature cattle. 108 61

Withholding iron dextran treatment normally given to pigs at 1-3 days of age to prevent anemia resulted also in neutropenia. Polyinosinic acid:polycytidylic acid (poly I:C) at 0.5 mg/kg IV at 25 days of age resulted in induction of putative interferon 2 to 24 hours later, with significantly (P less than 0.05) lower concentrations in iron-deficient (Fe-) female pigs than in iron-supplemented (Fe+) female pigs. Poly I:C caused several transient toxic manifestations, including elevations in blood urea nitrogen, creatinine, aspartate aminotransferase, potassium (K), total bilirubin and phosphorus (P), marked leukopenia (both neutropenia and lymphopenia), and declines in serum albumin, calcium, cholesterol, glucose and globulin. Certain blood chemistries before poly I:C were significantly (P less than or equal to 0.05) different: albumin, globulin, cholesterol and K were higher in females than in males; albumin, globulin, glucose, P and K were higher in Fe- than in Fe+ pigs; and total carbon dioxide was higher in Fe+ than in Fe- pigs.
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PMID:Effects of poly I:C in porcine iron deficient neutropenia. 241 Jan 86

Trimetrexate is a nonclassical antifolate with greater preclinical antitumor activity than methotrexate. Fourteen patients with stage III or IV non-small-cell lung cancer who had not previously received chemotherapy were given trimetrexate (12 mg/m2 intravenously daily for 5 days) every 3 weeks. No major objective responses were observed (95% confidence limits: 0-20%). Ten of the 14 patients had grade 2 or greater toxicity, with 50% experiencing grade 2 or greater leukopenia and/or thrombocytopenia. Nausea, vomiting, rash, mucositis, diarrhea, and serum glutamic-oxaloacetic transaminase (SGOT) elevations were also seen. At the dosage and schedule of trimetrexate used, no responses occurred in this population of patients with non-small-cell lung cancer. With the low response rate and the observed degree of myelosuppression, trimetrexate appears to have limited utility in this disease.
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PMID:Phase II trial of trimetrexate in patients with stage III and IV non-small-cell lung cancer. 253 13

Ten yearling white-tailed deer (Odocoileus virginianus) were inoculated with bluetongue virus serotype 17. Two yearling white-tailed deer were inoculated with sonicated heparinized noninfected blood and served as controls. Clinical signs of bluetongue virus infection included increased rectal temperature, erythema, facial edema, coronitis, and stomatitis. By postinoculation day (PID) 8, excessive bleeding and hematoma formation at venipuncture sites, dehydration, and diarrhea developed. At necropsy, the most consistent findings were oral lesions and widespread hemorrhage, which ranged from petechia to massive hematoma formation. Bluetongue virus caused progressive prolongation of activated partial thromboplastin time and prothrombin time, and progressive reduction of Factors VIII and XII plasma activities beginning on PID 6. A progressive decrease in platelet numbers also developed on PID 6. Changes in platelet size were not detected. Mean thrombin time was shortened, but prolongation developed in 1 deer. Mean fibrinogen concentration and Factor V plasma activity initially increased and then decreased, but remained above preinoculation values. Factor V activity was low in a few deer. Results of screening tests for inhibitors of the intrinsic coagulation system were positive in 2 deer. High concentrations of fibrin(ogen) degradation products were first detected between PID 3 and 6. Hematologic changes included leukopenia, lymphopenia, neutrophilia, and low total plasma protein concentration. Differences in PCV, hemoglobin concentration, or RBC counts were not detected between infected and control deer. Serum total bilirubin concentration increased by PID 6, primarily because of increased unconjugated bilirubin concentration. Mild to severe increases in serum aspartate transaminase activity were accompanied by more marked increases in creatine kinase activity. Indirect Coombs test results were negative in all deer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimentally induced bluetongue virus infection in white-tailed deer: coagulation, clinical pathologic, and gross pathologic changes. 285 9

Aztreonam was used successfully in 17 of 17 patients with orthopedic infections due to gram-negative bacilli (11, osteomyelitis; six, septic arthritis). Duration of treatment ranged from 14 to 55 days, and the period of follow-up was four to 18 months. Causative organisms included Pseudomonas aeruginosa, Serratia marcescens, Enterobacter gergoviae, Citrobacter diversus, Proteus mirabilis, and Enterobacter aerogenes. Aztreonam was well tolerated. The only definite reactions attributable to aztreonam were asymptomatic increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) in four patients; none of these reactions interfered with completion of therapy. Adverse reactions that were possibly attributable to aztreonam included rash (two patients), diarrhea (one patient), and leukopenia (one patient). All of these patients were receiving antibiotics active against gram-positive organisms in mixed infections in addition to aztreonam. Aztreonam is a promising new monobactam without significant toxicity. It has good activity against gram-negative aerobic bacteria, including P. aeruginosa, and is effective in the treatment of serious infections due to gram-negative aerobes.
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PMID:Aztreonam in the treatment of bone and joint infections caused by gram-negative bacilli. 293 86

We performed a phase I study of menogaril to determine if dosage reduction was required in patients with hepatic dysfunction and if the relationship between pharmacokinetics and leukopenia, previously defined in patients with normal hepatic and renal function, was altered. Eighteen patients received 27 courses of menogaril, of which 26 were evaluable for toxicity. Patient characteristics were median age, 63 years (range, 28-80 years), 14 male/4 female, and median Karnofsky performance status 80% (range, 60-100%). Prior therapy included none, five; chemotherapy only, seven; radiotherapy only, two; and chemotherapy and radiotherapy, four. Menogaril was administered as a 2-h.i.v. infusion every 28 days at 62.5 (one patient), 125 (eight patients), 187.5 (seven patients), and 250 mg/m2 (six patients), based on pretreatment serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Patients also had indocyanine green and antipyrine clearances measured before menogaril treatment. Menogaril and metabolites were assayed by high performance liquid chromatography. Dose-limiting toxicity was leukopenia. WBC nadirs occurred between days 8 and 20 (median, 15). Three patients developed platelet nadirs below 100,000/microliters. Other toxicities included grade I nausea and vomiting in three patients and phlebitis at the site of drug infusion in six patients. Correlations were defined between pretreatment indocyanine green clearance and serum concentrations of alkaline phosphatase and total bilirubin. There were no correlations between pretreatment serum concentrations of bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, indocyanine green clearance or antipyrine and menogaril clearances. Menogaril pharmacokinetics in patients with elevated liver function tests was indistinguishable from that described in patients with normal liver function tests. There were excellent correlations between plasma area under the curve of menogaril and the percentage decreases in WBC and neutrophils. These were well described by two models previously used to study the same relationships in patients with normal hepatic and renal function. When compared to previous studies, patients with hepatic and renal dysfunction had a greater percentage decrease in WBC for any given area under the curve than did patients with normal hepatic and renal function. On the other hand, there was no difference in the relationship between percentage decrease in neutrophils and menogaril area under the curve in these two groups of patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I study and pharmacokinetics of menogaril (NSC 269148) in patients with hepatic dysfunction. 295 59

10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a weekly x 3 schedule (35 patients) or a weekly schedule (27 patients). The dosage levels ranged from 5 to 120 mg/m2. The toxicity observed with 10-EDAM was qualitatively similar to that of methotrexate. Oral mucositis was the dose-limiting toxicity; diarrhea, skin rash, leukopenia, thrombocytopenia, and mild elevations of serum glutamic-oxaloacetic transaminase, prothrombin, and partial thromboplastin times were also observed, but were not dose limiting. A weekly dosage of 80 mg/m2 with escalation or attenuation in accordance with patient tolerance, or 100 mg/m2 weekly for 3 weeks, followed by a 2-week "rest period" are recommended for Phase II assessment. 10-EDAM produced partial remissions in three patients with non-small cell lung cancer and one patient with breast cancer lasting 6, 40+, 26+, and 15 months, respectively. Pharmacokinetic studies carried out at the 5, 30, and 100 mg/m2 dosage levels demonstrated the drug to have a triphasic disappearance from plasma. Elimination was independent of dose over the range tested, with mean plasma half-lives of: alpha = 12.9 min, beta = 1.5 h, and gamma = 11.9 h. Cumulative urinary excretion of the drug ranged from 13 to 55% of the administered dose (mean = 33%); 88% of the urinary drug appeared within the first 4 h following drug administration. The pharmacokinetic behavior of the first and second weekly dosages were consistent within a given patient. The metabolites 7-hydroxy-10-EDAM, and 10-ethyl-10-deaza-2,4-diamino-pteroic acid were demonstrated in the plasma and urine of treated patients. In studies of tissue homogenates from two patients with skin metastases, more extensive retention of the drug and of its polyglutamates was observed in the breast cancer metastases than in the metastases from a kidney cancer or in normal skin.
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PMID:Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer. 341 10

A 7-year-old adult male ferret had progressive hair loss that was bilaterally symmetric. Also clinically evident were severe dehydration, polydipsia, muffled heart sounds, weak femoral pulses, hepatomegaly, lethargy, weakness, temporal muscular atrophy, dyspnea, and weakness. The blood profile of the ferret indicated profound leukopenia, eosinopenia, and high phosphorus, BUN, creatinine, and potassium concentrations, as well as high aspartate transaminase activity; the albumin concentration was low. The serum cortisol concentration was 8.1 micrograms/dl. Necropsy and histologic findings confirmed a diagnosis of hyperadrenocorticism, complicated by dilatative cardiomyopathy, chronic active hepatitis, and renal disease.
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PMID:Hyperadrenocorticism in a ferret. 365 2

T-2 toxin was given as a single intravascular dose at either 0.6 or 4.8 mg/kg to different groups of 50-kg female swine. Blood samples were taken at hourly intervals for determination of concentrations or activities of the following substances in serum or plasma: creatinine, blood urea nitrogen, inorganic phosphorus, total calcium, ultrafilterable calcium, magnesium, sodium, potassium, chloride, total protein, albumin, cholesterol, glucose, alkaline phosphatase, aspartate aminotransferase, and total bilirubin. Coagulation analyses included prothrombin time, partial thromboplastin time, activated coagulation time, and fibrin degradation products. Red blood cell, white blood cell, and platelet counts, hemoglobin concentrations, and hematocrits were determined from whole blood samples. An initial leukocytosis was followed by a leukopenia. The numbers of red cells, the hemoglobin concentration, and the hematocrit were increased. Nucleated red blood cells were seen in the blood smears. The serum concentration of bound calcium decreased, while phosphorus, magnesium, and potassium increased. Clinical screening tests detected no evidence of a coagulopathy in swine given T-2 toxin intravascularly.
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PMID:Experimental T-2 toxicosis in swine. II. Effect of intravascular T-2 toxin on serum enzymes and biochemistry, blood coagulation, and hematology. 406 62


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