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)

In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease in p-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2 x MELD(10) (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i.e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity.
Cancer Chemother Pharmacol 1989
PMID:Nephrotoxicity of 5-(N-phenylcarboxamido)-2-thiobarbituric acid in the Fischer 344 rat. 259 97

In patients with chronic circulatory insufficiency, chronic nonspecific diseases of respiratory system, lung malignancies, as well as in the group of patients with "other diseases" complicated by bacterial pneumonia the total protein and protein fractions, bilirubin, activity of alanine aminotransferase and of aspartate aminotransferase in the blood serum has been determined. The control group consisted of analogous groups of patient without, however, bacterial pneumonia. It has been stated that in patients with lung cancer bacterial pneumonia has been accompanied by the increased concentration of beta-globulin and the decreased concentration of gamma-globulin. In other groups of patients the lowered concentration of albumin and the increased concentration of alpha-globulin has been observed. Chronic nonspecific diseases of respiratory system were, moreover, characterized by the increased concentration of gamma-globulin. In some groups of patients with secondary bacterial pneumonias if compare with analogous++ groups of patients without pneumonia the increased bilirubin concentration and increased activity of alanine aminotransferase and/or aspartate aminotransferase remaining however within normal range has been demonstrated.
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PMID:[Results of various biochemical studies in secondary bacterial pneumonia]. 263 Nov 44

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing a stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune disease and different malignancies. Recently, urinary neopterin levels have been found increased in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels have been measured in 23 cirrhotic patients (6 HBV related, and 17 cryptogenetic cirrhosis, 7 of them occurring in alcoholic subjects) and in 24 normal subjects. Mean values of serum neopterin were significantly increased in cirrhotics (3.92 +/- 3.28 ng/ml versus 1.24 +/- 0.51 ng/ml in controls, p less than 0.01). Serum neopterin values were not found to be significantly different in cirrhotics assessed in three different clinical classes according to Child's classification and in cirrhotics with and without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with the values of serum AST, ALT, ALP, GGT and gamma-globulin. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all stages of liver cirrhosis irrespective of its aetiology.
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PMID:Serum neopterin levels in liver cirrhosis. 263 48

Circulating immune complexes (CIC) were measured at the time of diagnosis in 81 patients with acute leukemia or blast crisis of chronic myeloid leukemia using precipitation by 3.75% polyethyleneglycol. Elevated CIC levels did not adversely influence complete remission duration and survival, patients with normal CIC levels exhibited mostly shorter remission and survival than those with elevated or borderline levels. No significant correlation was observed between CIC levels and Hb, WBC, CBC, platelet count, age, serum bilirubin, total protein, fibrinogen, AST and ALT levels, presence of hepatosplenomegaly and/or lymphadenopathy, HbSAg positivity, complete remission duration and survival. The lack of correlation may be caused by altered immune response in leukemic patients, but the obtained results may also be affected by the nonspecific nature of the method used for the detection. Simultaneous detection of CIC levels by multiple tests and evaluation not only of the number but also of the composition and size of CIC may decrease the incidence of false results. Nevertheless, only the establishment of antigen-specific assays may resolve the controversies in the detection of CIC and thus contribute to a more precise assessment of the role of CIC in prognosis of cancer, as well as to the verification of reliability of using CIC as a tumor marker.
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PMID:Circulating immune complexes in acute leukemia. 270 22

Even though HAV, HBV and HNANB viruses are responsible for most of the viral hepatitis cases, many other viruses have been reported to cause hepatic injury. These viruses may involve the liver, either as part of a systemic illness (e.g. EBV, CMV, HSV) or as the primary target organ (e.g. yellow fever virus, Lassa fever virus, Ebola virus). Clinically overt hepatocellular dysfunction is rare in such viral infections. Biochemical disturbance of hepatic functions shown, for example, by rises in AST and ALT, is a frequent event and indicates hepatic damage. Morphological changes of the liver include varying degrees of hepatic necrosis with a paucity of inflammatory activities. Intranuclear or cytoplasmic inclusion bodies may be characteristic findings in these diseases. Laboratory diagnosis depends upon serology and liver histology. Treatment is still largely supportive in most of these diseases, although recent trials of antiviral agents show promise against some viruses. Chronic sequelae, such as cirrhosis or hepatocellular cancer, are not encountered. More work is needed to elucidate the pathogenesis of hepatic injury in these illnesses.
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PMID:Viral diseases involving the liver. 282 80

Serum glutamyl transferase (gamma-GT), serum total protein, albumin, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), alkaline phosphatase and bilirubin were measured in 55 males and 45 females suffering from O. viverrini infection and in apparently healthy non-infected individuals. A decrease in total protein, albumin and bilirubin, as well as an increase in GOT, GPT and gamma-GT was observed in males with O. viverrini infection, whereas alkaline phosphatase remained unaffected. In female patients with O. viverrini, serum total protein and albumin also decreased, GOT and GPT increased, whereas gamma-GT remained unchanged. The difference in gamma-GT alteration between females and males is discussed with regard to the possible significance of alcohol consumption and in relation to the parasitic infection and its possible implications for malignancy, associated with liver fluke infection.
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PMID:Serum glutamyl transferase and other liver function tests in Opisthorchis viverrini infection. 286 Jul 15

Between December 1973 and September 1987, 21 patients with primary liver cancer and 41 patients with metastatic liver cancer were treated with external irradiation, intra-arterial infusion chemotherapy and/or transarterial embolization (TAE) at the National Medical Center Hospital, the National South Kyushu Central Hospital and the National Kure Hospital. Of the patients with primary liver cancer, 13 cases were treated with intra-arterial infusion chemotherapy (30-40 mg adriamycin or 10 mg mitomycin C) and hepatic irradiation. Eight cases were treated by TAE and hepatic irradiation. In the Child A group, the survival period of the chemotherapy + hepatic irradiation cases (mean: 608 days) was longer than that of the TAE + hepatic irradiation cases (mean: 216 days). The median survival period of all the cases was 7.0 months (mean: 10.9 months). For 16 of the 21 patients (who had absorbed over 40 Gy), the median survival period was 11.9 months (mean: 11.7 months). For 5 of the 21 patients (who had absorbed below 40 Gy), the median survival period was 4.3 months (mean: 7.9 months). Of the patients with metastatic liver cancer, the median survival period was 7.2 months (mean: 8.0 months). For 22 of the 41 patients (who had absorbed over 40 Gy), the median survival was 7.9 months (mean: 12.6 months). For 19 of the 41 patients (who had absorbed below 40 Gy), the median survival period was 1.7 months (mean: 2.6 months). The pretreatment serum GOT (glutamate oxaloacetate transaminase) levels and the pretreatment Karnofsky performance status index were the factors governing the prognosis of the cases with metastatic liver cancer, while toxicity was generally mild.
Cancer Chemother Pharmacol 1989
PMID:Hepatic irradiation in primary and metastatic liver cancer. 292 86

Fifty-one patients (16 with malignant extrahepatic biliary obstruction, ten with benign extrahepatic biliary obstruction, eight with alcoholic liver disease, five with viral hepatitis and 12 with liver metastases) and 19 adult healthy controls were studied with determinations of beta-N-acetyl hexosaminidase (a lysosomal enzyme which is cleared from the circulation by the Kupffer cells), carcinoembryonic antigen (CEA), serum bilirubin, alkaline-phosphatase and aspartate aminotransferase (AST). Both CEA and beta-NAH were elevated in each disease group. Elevated beta-NAH levels distinguished between benign and malignant extrahepatic biliary obstruction better than CEA levels. Beta-NAH levels for the malignant and the benign groups were 47.6 +/- 14.7 U/l and 23.0 +/- 4.7 U/l (mean +/- S.D.) respectively. The groups differed significantly (P less than 0.001). Plasma CEA levels for both groups were 18.7 +/- 38.9 and 7.2 +/- 3.3 ng/ml (mean +/- S.D.) respectively. Beta-NAH levels for the 19 normal controls were 15.8 +/- 3.5 U/l (mean +/- S.D.). Beta-NAH also was significantly elevated in patients with hepatic metastases (36.9 +/- 20.1 U/l). In 25 cancer patients with metastases other than in the liver beta-NAH levels (18.3 +/- 5.2) were not significantly elevated over the control group. It has potential value as a marker for non-CEA-producing liver metastases.
Eur J Cancer Clin Oncol 1985 Sep
PMID:Serum beta-N-acetyl hexosaminidase (beta-NAH) as a discriminant between malignant and benign extrahepatic biliary obstruction: comparison with carcinoembryonic antigen (CEA). 293 60

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)
Cancer Res 1987 Nov 15
PMID:Phase I study and pharmacokinetics of menogaril (NSC 269148) in patients with hepatic dysfunction. 295 59

3',5'-Dioctanoyl-5-fluoro-2'-deoxyuridine (FdUrd-C8), one of the lipophilic prodrugs of 5-fluoro-2'-deoxyuridine (FdUrd) was dissolved in an oily lymphographic agent (Lipiodol Ultra-Fluid), which had been studied as a carrier of the anticancer drug for hepatic cancer. The prodrug was administered into the left proper hepatic artery of rabbits bearing VX-2 tumor in the liver in order to examine the anticancer effects and possible adverse effects on nontumorous hepatic cells. Lipiodol or FdUrd-C8*Lipiodol selectively remained in the hepatic cancer area but disappeared from nontumorous parts of the liver 7 days after injection. Tumor growth rates in 1 week of the untreated group, a group given injections of 0.2 ml of Lipiodol alone, and groups given injections of 0.2 ml of Lipiodol containing 30, 50, 70, and 100 mg of FdUrd-C8 were 636, 436, 34.8, 14.9, -2.4, and -10.4% of the size at the time of treatment, respectively. Pathological observation also showed that FdUrd-C8 had a strong anticancer effect on VX-2 tumor growing in the liver of the rabbits. In contrast to the effect on the cancerous cells, that on nontumorous hepatic cells was very slight. In pathological observation, necrosis or degeneration of nontumorous hepatic cells was hardly observed. Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels temporarily rose 1 day after injection but returned to the initial levels within 7 days in all groups.
Cancer Res 1987 Apr 01
PMID:Selective anticancer effects of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine, a lipophilic prodrug of 5-fluoro-2'-deoxyuridine, dissolved in an oily lymphographic agent on hepatic cancer of rabbits bearing VX-2 tumor. 302 18


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