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

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

Conventional staging in small cell lung cancer (SCLC) is only of limited prognostic value and is often based on elaborate investigations. We have carried out univariate and multivariate analysis of possible prognostic factors at presentation in 333 consecutive patients with SCLC. Fifteen parameters were found to have individual prognostic significance, of which the most powerful were serum albumin, bone marrow aspirate, disease extent and performance status (all P less than 0.00005). Factors which were not of prognostic significance included age, sex, SVC obstruction, and pleural involvement. Multivariate analysis excluded many factors including bone marrow aspirate as not being independently variable, and a simple combination of clinical performance status, serum albumin and alanine transaminase could be used to define 3 groups (good; medium; poor) of better prognostic significance (survival at 1 year 50% vs. 27% vs. 3%) than conventional limited/extensive disease staging (1 year survival 48% vs. 18%). Other simple combinations of biochemical parameters including plasma sodium and alkaline phosphatase achieved almost as good prognostic groupings. We suggest that consideration should be given to replacing the conventional limited/extensive disease staging system with a simpler system along the lines we have described.
Eur J Cancer Clin Oncol 1987 Nov
PMID:Prognostic factors in small cell lung cancer: a simple prognostic index is better than conventional staging. 282 70

Members of four families segregating for multiple endocrine neoplasia type IIa (Sipple's syndrome) were typed for 16 segregating blood group, erythrocyte enzyme, and plasma protein loci. Linkage analysis failed to find evidence favoring linkage between the multiple endocrine neoplasia mutation and any segregating marker. The data from this study were combined with the published data to rule out linkage for the HLA, ABO, Rh, or MNS loci at theta less than or equal to 0.25, the ADA, PGMI, AcP, GLOI, or GM loci at theta less than or equal to 0.10, and for GPT, PGD, or HpA at theta less than or equal to 0.05. The pooled data are inconclusive with respect to the previously suggested linkage to the P blood group locus.
Cancer Genet Cytogenet 1985 Feb 15
PMID:A linkage study of multiple endocrine neoplasia type IIa. 285 92

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

Twelve patients with disseminated breast cancer were injected with monoclonal antibody MBr1 at the National Cancer Institute of Milan, Italy, from January 1983 to March 1985. The first seven patients had advanced disease and the remaining five operable breast cancer. In the first seven patients the initial dosage of MBr1 was 0.5 mg and was doubled in the next patient up to 16 mg. The last five women received 10 mg of MBr1. No general side effects such as bronchospasm, hypotension, immediate or delayed allergic reactions were observed. Four patients who were injected with 10 mg or more experienced fever, shudder and vague abdominal and articular pain. The following tests were monitored: R.B.C., W.B.C., percentage of lymphocytes, blood glucose, urea nitrogen and creatinine, serum levels of Na+, K+, Cl-, total proteins levels, albumins and globulins, bilirubin, GOT, GPT, alkaline phosphatase, LDH, amylase, gamma GT and CPK. No major modifications were observed: a limited increase of the transaminases, LDH and gamma GT was evident at the last check. An early temporary alteration of CPK was observed in the four patients who had symptoms. Serum levels of MBr1 are detectable immediately after injection starting from 4 mg, and all sera were negative 48 hours later. It is concluded that the scanty toxicity allows to continue clinical investigations to verify the linkage between MBr1 and Ca-MBr1 "in vivo" after a single injection of no more than 16 mg of the MoAb. The increase of this dosage as well as multiple injections do not seem safe at present.
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PMID:Evaluation of toxic effects following administration of monoclonal antibody MBr1 in patients with breast cancer. 287 47

For the investigation of locoregional chemotherapy of liver neoplasms we developed a standardized animal model in the rat. Continuous infusion therapy or repeated bolus injections of FUDR or 5-FU were given via the hepatic artery, the portal vein or the vena cava in tumor-bearing animals. The efficacy of the treatment was determined by measuring the tumor volume 3 weeks after tumor cell implantation. For the evaluation of the local and systemic toxicity serum GOT, GPT, and total bilirubin were determined. DNA single strand breaks were assessed in isolated liver and bone marrow cells. Inhibition of colony formation of bone marrow stem cells was determined by CFU-C and CFU-S bioassay. A significant reduction of tumor growth was observed only after continuous infusion of FUDR via the hepatic artery. Systemic toxicity was lowest in this group for both compounds while the local liver toxicity was only slightly elevated.
J Cancer Res Clin Oncol 1986
PMID:Experiments on the efficacy and toxicity of locoregional chemotherapy of liver tumors with 5-fluoro-2'-deoxyuridine (FUDR) and 5-fluorouracil (5-FU) in an animal model. 293 47

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

GR-C507/75 (GR38032F) antagonizes the 5-HT3 (serotonin) receptor and prevents cisplatin-induced emesis in animals. In this dose-ranging trial, 44 patients with cancer receiving chemotherapy known to produce nausea and vomiting (including cisplatin, cyclophosphamide, and doxorubicin) received three intravenous (IV) infusions of GR-C507/75 every two hours beginning 30 minutes before chemotherapy. Ten dosage levels were explored, ranging from 0.04 mg/kg to 0.35 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, headache, transient elevations of SGOT or alanine aminotransferase (ALT), and dry mouth. No akathisia or acute dystonic reactions were observed. Antiemetic effects were seen in patients receiving cisplatin at 120 mg/m2. GR-C507/75 can be safely administered on this schedule at IV dosages up to 0.35 mg/kg in patients receiving chemotherapy. Further studies of this agent at higher dosages and by different schedules are appropriate.
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PMID:Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy. 296 55

Four brothers who developed testicular neoplasms, one bilaterally, are described. Histologic examination showed four of the tumors to be seminomas and one to be a mixed germ cell tumor. Three of the brothers are alive. Apart from a late-onset bladder carcinoma in their father and a pulmonary cancer in a maternal uncle, cancers were not recorded in the extended kindred. One patient, a sister, and the parents had normal frequency of sister chromatid exchange (SCE) and chromosome aberrations, whereas the two patients sampled after radiation showed increase in one or both. The father was found heterozygous in 12 and the mother in 8 genetic marker systems among 25 tested. For the blood group gene loci JK and MNSs, and the erythrocyte enzyme locus GPT the father had given the same allele to all three affected sons examined. The mother had given different alleles to the sons in all of her informative markers. On the model of a recessively acting susceptibility gene, only JK and GPT remained consistent with linkage without recombination. These investigations did not add support to a genetic etiology for the unusual family occurrence of testicular cancer. An apparent birth-order effect on time at onset/diagnosis in this and published families suggests time-limited environmental factors. Nevertheless, JK, MNSs, and GPT should be included in future testis cancer families to test the model of a "dominant" genetic predisposition.
Cancer 1985 May 01
PMID:Testicular neoplasms occurring in four brothers. A search for a genetic predisposition. 298 72

A clinical phase II study of recombinant human leukocyte interferon A (rIFN-alpha A, Ro 22-8181) for various skin malignant tumors was jointly conducted at nine medical institutes across the country in order to study its clinical effect and side effects. Patients received Ro 22-8181 alone in doses ranging from 3 X 10(6) U/day to 50 X 10(6) U/day either by intramuscular injection or by local injection. Good response was obtained in one (4.8%) of 21 patients treated by intramuscular injection and in 26 (72.2%) of 36 patients treated by local injection. The percentage of good responses achieved by local injection for individual diseases was 55.6% (5/9) for metastatic malignant skin melanoma, 100% (11/11) for cutaneous malignant lymphoma, 100% (5/5) for extramammary Paget's disease, 75% (3/4) for intraepidermal cancer and 50% (2/4) for metastatic skin cancer. Main side effects were fever, anorexia, general fatigue, chills, nausea and vomiting. Abnormal laboratory data included leukopenia, and elevation of GOT and GPT, although their incidence was lower with local injection than with intramuscular injection. Side effects were mostly improved by reduction of the dose or discontinuation of the treatment.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in skin malignant tumors]. 298 7


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