Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sera of 260 patients with high serum aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1; AST)/alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2; ALT) ratio (greater than 2.0) and high serum AST (greater than 45 IU/1) were selected and tested for the presence of immunoglobulin complexed-AST, by using immunoprecipitation reaction and counterimmunoelectrophoresis. The macromolecular AST was confirmed by size-exclusion high-performance liquid chromatography (HPLC). 34 patients out of 260 were found to have AST-immunoglobulin complexes (13.1%). The classes of AST-linked immunoglobulins were identified to be alpha in 28 cases (82.4%, P less than 0.01), mixed type of alpha and gamma in 5 cases (14.7%) gamma in one case (2.9%). Positive frequency was the highest in liver malignancies, either primary (9/26, 34.6%) or metastatic (7/17, 42.2%), followed by other malignancies (6/55, 10.9%) and chronic liver diseases (4/22, 18.2%). Thus, it can be strongly suggested that the immunoglobulin A complexed-AST is frequently found in association with liver malignancies.
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PMID:Incidence and properties of aspartate aminotransferase-immunoglobulin complexes in patients with a high serum aspartate to alanine aminotransferase ratio. 220 38

In patients with either bilateral renal malignancies or with carcinoma occurring in a solitary kidney, the principle of en bloc removal of the tumor-bearing kidney cannot be applied. Recently we have performed surgical enucleation in two cases of asynchronous bilateral renal cell carcinoma. Case 1. A 60-year-old woman was hospitalized with diagnosis of left renal tumor 10 years tumor 10 years after right nephrectomy for renal cell carcinoma. The tumor was enucleated while occluding the renal vessels. Pathological examination revealed that the tumor (a nodule of 35 g) was renal cell carcinoma of grade I and perfectly covered by pseudocapsule. Hemodialysis was not required. The patient has been well for more than 11 months postoperatively and Ccr is 65 ml/min. Case 2. A 62-year-old man with slight elevation of serum GOT and GPT level was examined by CT, which revealed a space occupying lesion in the left kidney. He had undergone nephrectomy for renal cell carcinoma of right kidney 11 years ago. Three nodules of 56 g, 6 g and 3 g were removed by in situ enucleation. They were renal cell carcinoma of grade II and there was no malignant penetration of the pseudocapsule pathologically. After surgery hemodialysis was required 10 times for 21 days. Renal function has been refined gradually and the patient is well with 47.3 ml/min of Ccr at 4 months postoperatively. Before this report of 2 cases there were 22 cases of asynchronous bilateral renal cell carcinoma in Japanese literature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of asynchronous bilateral renal cell carcinoma. On our experience of enucleation for two cases]. 221 72

The effects of dietary thiamin, riboflavin and pyridoxine deficiencies on dimethylnitrosamine-induced lethality and hepatotoxicity were investigated in the rat. Development of deficiencies was monitored by growth rate, food intake, ratio of liver weight to body weight and the biochemical parameters (thiamin diphosphate effects for thiamin deficiency, glutathione reductase activity coefficient for riboflavin deficiency and erythrocyte glutamate-oxaloacetate transaminase activity for pyridoxine deficiency). Thiamin deficiency slightly increased the acute toxicity of dimethylnitrosamine as observed by the lowering of the LD50 dose and the greater increase in the serum glutamate-oxaloacetate transaminase and serum glutamate-pyruvate transaminase levels. Riboflavin deficiency, on the other hand, slightly increased the LD50 dose of dimethylnitrosamine and resulted in less dimethylnitrosamine-induced damage to the liver. Pyridoxine deficiency did not affect the lethal dose nor significantly alter the transaminases levels.
J Cancer Res Clin Oncol 1990
PMID:Alterations in dimethylnitrosamine-induced lethality and acute hepatotoxicity in rats during dietary thiamin, riboflavin and pyridoxine deficiencies. 225 78

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.
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PMID:[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies]. 226 Aug 76

The effect of the administration of an extract of garlic (Allium sativum) was studied in mice that were treated with a chronic lethal dose of cyclophosphamide (50 mg/kg body wt, 14 days). The intraperitoneal administration of garlic (50 mg/animal, 14 days) along with cyclophosphamide reduced the toxicity of the latter considerably with an increase in life span of more than 70%. The administration of garlic extract did not improve the lymphopenia produced by cyclophosphamide or liver alkaline phosphatase, but there was a significant reduction in liver glutamic-pyruvic transaminase. Moreover, garlic extract reduced the level of lipid peroxidation induced in the liver by cyclophosphamide administration. Administration of garlic extract did not interfere with the tumor-reducing activity of cyclophosphamide.
Nutr Cancer 1990
PMID:Chemoprotection of garlic extract toward cyclophosphamide toxicity in mice. 230 75

cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ +(II) (NDDP) is a liposome dependent cisplatin analogue since the liposome carrier is required for its i.v. administration and for its biological activity. A Phase I study of liposome entrapped NDDP (L-NDDP) was performed using a single i.v. injection every 4 weeks. L-NDDP was prepared and characterized at M. D. Anderson Cancer Center. The maximum tolerated dose of L-NDDP was 312.5 mg/m2. The dose-limiting toxicity was myelosuppression, affecting all three blood cell lineages. The granulocyte nadir occurred on days 14-18, and the platelet nadir consistently earlier (days 11-12). The median day of recovery of blood cell counts was day 21 (range, 18-32). Other toxicities included grade 2 nausea and vomiting, fever consisting of a single temperature spike in most patients, grade 1 diarrhea after 60% of courses, and grade 1-2 malaise lasting for 5-10 days after the infusion in 73% of courses. Transient alanine aminotransferase elevations without clinical relevance were common. No signs of renal dysfunction or ototoxicity were observed. One patient with a preexisting peripheral neuropathy showed some progression of the neuropathy after a cumulative dose of 1605 mg/m2. Except for fever and transient liver dysfunction, no liposome related side effects were observed in spite of the high doses of lipid administered. The blood clearance of L-NDDP fits a two-compartment model at lower doses and a single-compartment model at the maximum tolerated dose, suggesting that saturation of the reticuloendothelial organs occurs at the maximum tolerated dose. Two minimal responses were observed. L-NDDP has a toxicity profile similar to that of carboplatin. Phase II studies to address the issue of how the therapeutic index of platinum compounds is affected by liposome entrapment are being planned.
Cancer Res 1990 Jul 15
PMID:Phase I clinical and pharmacological study of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II). 236 84

We measured aminotransferase activity and vitamin B6 content in the livers of diabetic mice. Two different types of mice were used for the measurements, spontaneously non-obese diabetic (NOD) or alloxan-induced diabetic (Allo) mice, and control mice were either non-diabetic NOD or Institute of Cancer Research (ICR). The liver of diabetic mice had more aspartate aminotransferase (AST) activity than those of normal mice. The diabetic livers also had more vitamin B6 than did normal livers, and pyridoxamine (PM) levels were particularly high but pyridoxal (PL) levels were not. ICR livers showed hepatic alanine aminotransferase activities inversely correlated with blood glucose concentrations, while diabetic livers did not. The abundance of AST and B6 in the diabetic liver is consistent with the great need for gluconeogenic substrate there. This is understandable in that most aminotransferases require B6 vitamins, and especially the correlation between s-AST and PM levels was recognized in the diabetic liver. Conversely, the AST and PM levels were negatively correlated in normal mice. A metabolic shift towards gluconeogenesis apparently produces more B6 and PM while it induced holo-AST synthesis.
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PMID:Changes on levels of B6 vitamin and aminotransferase in the liver of diabetic animals. 237 34

The aim of this study was to determine the mechanism by which bropirimine exerts its developmental toxicity. This drug is an immunomodulator and interferon inducer with antiviral and antitumor activities in experimental models. Timed-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats were given a single oral (gastric intubation) dose of bropirimine at 200 or 400 mg/kg (doses as high as 100 mg/kg/day have been employed in human cancer trials) on days 5, 6, 7, 8, 9, 10, 11, or 12 of gestation and in a second experiment on day 12, 13, 14, 15, 16, 17, 18, or 19 of gestation. The dams were killed 24 hours after dosing and their uterine contents examined. In a third experiment, bropirimine (400 mg/kg) was administered on day 4 of gestation and the uteri of different groups were examined on day 8, 9, 10, 11, or 12 of gestation. Serum progesterone levels were measured at sacrifice. In the first two experiments a battery of hematologic/clinical chemistry assays also were performed. In all three experiments, bropirimine-related maternal toxicity was observed; such toxicity was characterized by significant decreases in weight gain, relative to the concurrent vehicle controls, as well as significant differences in several blood parameters including platelets, white blood cells, alanine aminotransferase, and aspartate transaminase. In the first experiment, bropirimine treatment on day 11, but not day 12, resulted in significant decreases in the mean number of live embryos per litter. In the second experiment, significant decreases in the number of live fetuses per litter occurred 24 hours after dosing on day 18 (200 and 400 mg/kg groups) or day 19 (400 mg/kg group). Decreases in serum progesterone appeared to correlate well with the embryolethal effects seen after treatment between days 6 and 11 of gestation, but not with the fetal lethality seen when treatment was given on day 17 or 18. The decreases in serum progesterone levels found most likely were the result of a luteolytic effect, although it is unknown if bropirimine has a direct or indirect effect on the corpora lutea. In the third experiment, bropirimine treatment on day 4 of gestation resulted in only slight preimplantational losses, but significant decreases were found in mean number of live embryos per litter after day 9. Uterine decidual necrosis has been observed in the first experiment where bropirimine was given on day 11; however, treatment on day 4 resulted in an apparent decrease in decidual development but not necrosis.
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PMID:Variability in the developmental toxicity of bropirimine with the day of administration. 239 79

Female Sprague-Dawley rats were given 0, 168, 840, 2550 or 4200 mg/kg of 1,4-dioxane 21 and 4 h before sacrifice. Hepatic DNA damage (by the alkaline elution technique), ornithine decarboxylase activity (ODC), reduced glutathione content, cytochrome P-450 content and serum alanine aminotransferase activity (ALT) were determined. Treatment with 1,4-dioxane increased hepatic DNA damage and cytochrome P-450 content at doses of 2550 and 4200 mg/kg. Large increases in the activity of hepatic ODC were observed at 840, 2550 and 4200 mg/kg of 1,4-dioxane. Thus the data suggest that 1,4-dioxane is a weak genotoxic carcinogen in addition to being a strong promoter of carcinogenesis (a non-genotoxic carcinogen).
Cancer Lett 1990 Aug
PMID:Is 1,4-dioxane a genotoxic carcinogen? 239 85

Postoperative intraportal anti-cancer chemotherapy was used for 51 patients with curatively resected colorectal cancer who were selected in the randomized controlled study to evaluate its inhibitory effect on liver metastasis from colo-rectal cancer. In cases of intraportal chemotherapy, 30 mg of Mitomycin-C (in 3 doses) and 5 mg/kg (B.W.)/day (1985-1986) or 3 mg/kg/day (1987-1988) of 5-FU was injected through the catheter inserted into the portal vein during postoperative 14 days. In cases of the control group (58 patients), the same doses of the drugs were injected into the peripheral vein during the same term. Six patients with recurrences were observed in the intraportal chemotherapy group, and 3 of them had liver metastases. In the control group, more liver metastases were observed (5 of 7 recurrences were liver metastases). Intraportally injected 5 mg/kg/day of 5-FU slightly disturbed the liver function. The averages of the serum GOT, GPT and gamma-GTP level of these cases were higher than those of the control cases. Three mg/kg/day of intraportally injected 5-FU had no influence on the liver function. There were no differences in the incidence of leukocytopenia or thrombocytopenia between the two groups.
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PMID:[Effects of prophylactic intraportal chemotherapy on liver function, blood profile and survival in patients with colo-rectal cancer]. 250 34


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