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)

A total of 203 paediatric cancer treatment survivors were tested for serum antibodies against hepatitis-C virus (anti-HCV). Anti-HCV was detected in 41 patients (20.2%) with first generation anti-HCV ELISA. Positive results were confirmed in all samples retested with a second generation ELISA (n = 35) and in all but two cases re-analysed by immunoblotting (n = 23). Anti-HCV positive children had received significantly more blood product transfusions compared to seronegative patients. In 75 children (32%) chronic liver disease was found. It was defined as an elevation of serum alanine aminotransferase values to a least 2.5 times the upper limit of normal persisting for 6 months or longer. Hepatitis A was never detected, and in 58 children the chronic hepatopathy was unexplained by hepatitis B (non-A non-B chronic liver disease). Of these patients 29 (50%) were seropositive for anti-HCV. Surprisingly, non-A/non-B chronic liver disease was associated with anti-HCV in 14 of 19 solid tumour patients (78.9%), but in no more than 14 of 39 leukaemia and lymphoma patients (35.9%). This phenomenon was not explained by different rates of cytomegalovirus disease and drug toxicity related hepatopathies between the two groups. It may be related to differences of leukaemia/lymphoma compared to solid tumour therapy schedules (differential immunosuppression and liver toxicity).
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PMID:Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients. 768 44

We used the polymerase chain reaction (PCR) to determine the presence of hepatitis C virus (HCV)-RNA in serum samples obtained from 19 patients with leukaemia or severe aplastic anaemia and investigated the correlation between HCV status and the results of liver function tests after bone marrow transplantation. PCR analysis of serum samples obtained before transplant showed that 10 of 18 patients were HCV-RNA-positive; 5 of these patients had developed acute post-transfusion hepatitis 1-11 months before transplant. An additional patient was HCV-RNA-positive on post-transplant day 62. Eight HCV-RNA-positive patients had pre-transplant GPT levels above the upper limit of normal. In these patients the GPT decreased significantly from a median of 104 IU/l (54-822 IU/l) pre-transplant to 23 IU/l (15-56 IU/l) on post-transplant days 8-12. In 9 of 11 HCV-RNA-positive patients, the GPT increased transiently from days 40 to 50 and again increased after day 100. Two of these patients died from hepatic failure; the GPT levels normalised in 3 patients after day 300 but continued to fluctuate in 4 patients. In the remaining 2 HCV-RNA-positive patients, the GPT remained close to the normal range throughout the follow-up period. Three HCV-RNA-positive patients became HCV-RNA-negative after 1-3 years. In these patients, the GPT remained normal for > 3 years after day 300.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver function tests of recipients with hepatitis C virus infection after bone marrow transplantation. 801 65

The cytotoxic activity of 6-mercaptopurine (6-MP) is affected by thiopurine methyltransferase (TPMT), a genetically regulated and variable intracellular enzyme. 6-Thioguanine (6-TG), a closely related thiopurine, is less affected by that enzyme and so it may be a more reliable drug-at least for patients with constitutionally high TPMT activity. We attempted to assess its suitability as an alternative by comparing the pharmacokinetics of both drugs in a small group of children with lymphoblastic leukaemia (ALL). Patients were included who were in their second or subsequent remission, who would otherwise have received 6-MP, and on whom pharmacokinetic data concerning 6-MP metabolism had been collected in a previous remission. Plasma 6-TG concentrations were assayed following an oral dose of 40 mg m-2, and the accumulation and fluctuation of intracellular (erythrocyte, RBC) 6-TG nucleotides (6-TGNs) were measured at regular intervals during daily oral therapy. Seven children were studied. Plasma 6-TG concentrations were low and cleared within 6 h of oral dosing. At 7 days, 6-TGN concentrations ranged from 959 to 2361 pmol 8 x 10(-8) RBCs, in all cases significantly higher (P = 0.002) than those produced by the same patients on 6-MP. After a total therapy time of 35 patient months, a modest rise of alanine aminotransferase was seen on one occasion, otherwise no toxicity apart from myelosuppression was encountered. In the context used, 6-TG appears well tolerated and produces higher concentrations of intracellular cytotoxic metabolites than 6-MP. For children constitutionally 'resistant' to the traditional drug, if not all, it may be a preferable alternative.
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PMID:Is 6-thioguanine more appropriate than 6-mercaptopurine for children with acute lymphoblastic leukaemia? 831 12

The presence of viruses in blood cells or plasma from asymptomatic donors is the major risk of transmitting an infectious agent through blood transfusion. The main viruses involved are hepatitis viruses and retroviruses. The risk of transmitting hepatitis B virus (HBV) and hepatitis C virus (HCV) has been progressively and efficiently reduced in the last years by the successive introduction of hepatitis B surface antigen (HBsAg) screening, elevated serum alanine aminotransferase (ALT), antibody to hepatitis B core (HBc Ab), and more recently antibody to hepatitis C virus (HCV Ab). The risk of transmitting human retroviruses like human immunodeficiency virus (HIV) and human T-cell leukemia/lymphoma virus (HTLV) has also been reduced drastically thanks to screening for corresponding antibodies. However, except for HBs Ag screening, the immunoassays used for HCV, HIV, or HTLV only detect antibodies. Therefore, although they are infectious, a few blood units may be not discarded. The efficacy of preventive measures depends on the incubation time, the infectivity during this silent phase, and the sensitivity of screening procedures. Human cytomegalovirus (HCMV) and parvovirus B 19 are responsible for common infections. Consequently, 30% to more than 50% adults have serologic evidence of past infection. However, both viruses may cause severe primo-infections in some circumstances, especially in pregnant women or immunodeficient individuals.
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PMID:[Viral risks associated with blood transfusion]. 838 12

This review summarises serologic profiles and clinical features of HCV infection in children with leukemia. The diagnosis of HCV infection is currently based on the detection in serum of antiviral antibodies and HCV-RNA. Studies on leukemic children, however, have clearly shown that only HCV-RNA testing correctly identifies HCV infection, as specific antibodies become detectable in serum only after chemotherapy withdrawal in almost all cases. Viraemia instead appears early in the course of leukemia, and infected patients become carriers. The pattern of liver disease is rather homogeneous. Early onset, persisting ALT elevation during chemotherapy often with drastic reduction during high-dose chemotherapy, followed by sharp exacerbations of liver cell necrosis. ALT normalise after chemotherapy withdrawal in most cases, despite persisting viraemia. As regards to the ultimate prognosis of liver disease in these children, we have observed that, among a series of 119 patients followed for at least 10 years off-therapy, none has developed clinical decompensated liver disease and only 6% still has abnormal ALT levels. On the other hand, the need for prolonged follow-up of children surviving leukemia with chronic HCV infection is emphasized by the fact that the natural history of HCV infection has not been fully clarified and that additional late sequelae are likely to occur.
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PMID:Hepatitis C virus serum markers and liver disease in children with leukemia. 858 Jul 92

We have evaluated the efficacy of treatment with recombinant Interferon-2b (IFN-2b) in 12 children with cancer who developed chronic hepatitis-B infection. Seven of them had lymphoblastic leukaemia and others had solid tumours. Seven cases were male. Mean age was 10.5 years with a range of 5-16 years. Chronic Hepatitis B was diagnosed biochemically, serologically and histopathologically. They were HBsAg(+), HBV-DNA(+), and HCV(-), HIV(-). Seven cases were HBeAg(+) and two of them were anti-Delta IgG(+). Liver biopsy revealed chronic active hepatitis in six cases and persistent hepatitis in three cases. IFN was given at the dose of 5 MU/m2 three times a week, subcutaneously for 6 months. It was well tolerated. After IFN therapy, ALT levels returned to normal in seven cases. All cases were still HBsAg(+). Four of them seroconverted to anti-HBe antibody. Loss of serum HBV-DNA in three cases, but 11 cases showed a marked decrease after IFN. The control liver biopsies showed that histopathological activity index was diminished in five cases. Other 16 patients, serving as control, received no therapy. Five of them were leukaemia and others were solid tumours. Twelve cases were male. Mean age was 9.3 years with a range of 4-19 years. After 6 months, only one patient lost HBV-DNA and three of them seroconverted to anti-HBe with normalization of ALT values. In our study, IFN treatment favourably influenced the progress of chronic hepatitis B in children with cancer.
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PMID:alpha-Interferon-2b treatment for chronic hepatitis-B infection in children with cancer. 893 55

Bropirimine (U-54461S), an oral interferon (IFN) inducer that has also a direct antiproliferative activity, is a novel antitumor agent. To investigate the safety and pharmacokinetics of bropirimine tablets and to measure IFN concentrations in patients with cancer, Phase I studies were conducted. In single dose study (0.25 to 3g) and multiple-dose study with one-day dosing (1 or 2g, every one or two hours, three times a day), bropirimine treatment was well tolerated by the patients with cancer. In multiple-dose study with consecutive days dosing (1 or 2g, every 2 hours, three times a day for 3 or 5 consecutive days), a regimen with a dose of 1g orally administered every two hours, three times a day for three consecutive days was considered to be tolerable to cancer patients. Adverse drug reactions frequently observed were generalized malaise, fever, nausea/vomiting, anorexia, headache/dull headache, and tachycardia. Abnormalities in laboratory tests frequently observed were leukemia, neutropenia, thrombocytopenia, and elevation in GOT/GPT. IFN was not induced in any patients in the single dose study. It was, however, induced in 3 of 16 cases (18.8%) in the one-day dosing study and in 6 of 7 cases (85.7%) in the consecutive days dosing study. As to clinical antitumor efficacy, a decrease in size of the tumor lesions and improvement in subjective/objective symptoms were noted in two cases in the one-day dosing study. With these findings, the regimen with the dose of 1g orally administered every two hours, three times a day for three consecutive days with a four-day drug-free interval per week was recommended for early phase II studies.
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PMID:[Bropirimine (U-54461S) phase I clinical studies]. 897 2

We examined 111 patients with acute type- or lymphoma type-adult T-cell leukemia (ATL) and compared them with 106 patients with non-Hodgkin's lymphoma (NHL). In addition to skin involvement and hypercalcemia which are already known to be frequent in ATL, ATL patients showed an higher incidence of hepatic involvement. There was more frequent palpable hepatomegaly, higher total bilirubin, GOT, GPT, lactate dehydrogenase (LDH), and alkaline phosphatase values in ATL than in NHL patients (p < 0.0001). Among 36 autopsied liver samples, invasion of ATL cells was confirmed in 22 cases. ATL patients with impaired hepatic function showed shorter survival times than patients without hepatic dysfunction. Moreover, ATL patients showed a worse performance status (PS), a higher incidence of lytic bone lesions, lower total protein (TP) and serum albumin levels than NHL patients. This invasive characters of ATL cells and consequent impaired general condition seemed to be factors affecting the poor prognosis recorded in ATL.
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PMID:Frequent hepatic involvement in adult T cell leukemia: comparison with non-Hodgkin's lymphoma. 932 95

Neoplastic disorders sometimes accompany a renal transplant. Herein, we report a large granular lymphocyte (LGL) leukemia patient with pure red cell aplasia (PRCA) after renal transplantation. A 36-year-old female was presented to our department with anemia in February 1996. She had undergone hemodialysis because of pregnancy in December 1981. She received a renal transplantation from her mother in April 1986. After the transplantation, she received cyclosporin A (CyA) at 2 mg/kg/day, mizoribine at 1 mg/kg/day, and methylprednisolone at 0.1 mg/kg/day for 8 years. In July 1995, her hemoglobin level dropped to 9.3 g/dl, and anemia developed gradually. In January 1996, her hemoglobin was 5.8 g/dl, and she was given a red blood cell transfusion. Laboratory findings were as follows: RBC 1.46 x 10(12)/L; hemoglobin 5.8 g/dl; hematocrit 17.8%; leucocytes 5.2 x 10(9)/L with 62.4% neutrophils, 34.1% lymphocytes, 2.6% monocytes; platelets 50.8 x 10(10)/L; reticulocytes 0.4%. Bone marrow aspirate smears and biopsy sections revealed normal myeloid and megakaryocyte differentiation with few erythroid precursors. The lymphocytes were of medium size with granules in the cytoplasm. More than 90% of lymphocytes were of the LGL type. Surface markers of peripheral blood mononuclear cells demonstrated increases in the CD2+, CD3+, CD4-, and CD8+ populations. A monoclonal rearrangement of T-cell receptor (TCR)-beta chain gene was found by Southern blot analysis of the mononuclear cells in peripheral blood. A diagnosis of LGL leukemia with PRCA was made. During the next 4 months, she received six red blood cell transfusions, a total of 12 U. In March 1996, the patient was treated with cyclophosphamide (1 mg/kg/day). After 1 month of treatment, serum GPT levels increased to 60 IU/l. The dose of cyclophosphamide was reduced to 0.5 mg/kg/day. Two months after initiation of the therapy, the patient developed reticulocytosis and blood transfusion was not needed thereafter. During remission, the number of CD2+, CD3+, CD4-, and CD8+ lymphocytes decreased. Large granular lymphocytes decreased to less than 10% of peripheral blood. The monoclonal rearrangement of the TCR-beta chain gene in peripheral blood disappeared.
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PMID:Large granular lymphocyte leukemia with pure red cell aplasia in a renal transplant recipient. 942 21

We have previously shown, using human T-cell lymphocytotrophic virus-I (HTLV-I)-infected cell lines, that soluble interleukin-6 receptor (sIL-6R) is generated through an alternative splicing mechanism. In this study, we examined human sera for the presence of alternatively spliced soluble IL-6R (AS-sIL-6R). We produced a monoclonal antibody (mAb) recognizing the unique sequence of AS-sIL-6R peptide, generated by an altered reading frame. We also made recombinant AS-sIL-6R protein in Spodoptera frugiperda-9 (Sf-9) cells carrying baculovirus, which encoded altered sIL-6R or conventional IL-6R cDNA. mAbs specifically recognized AS-sIL-6R, but not conventional IL-6R, as demonstrated by Western blot analyses, fluorescence-activated cell sorter, immunofluorescence analyses and enzyme-linked immunosorbent assay (ELISA). We adapted an ELISA system and used it for detection of altered sIL-6R in sera from 23 healthy persons, 12 patients with adult T-cell leukaemia (ATL) and 13 patients with HTLV-I-associated myelopathy (HAM). Serum levels of AS-sIL-6R were 6.4 or 6.1 times greater in ATL (28.7+/-20.4 ng/ml, P<0.0001) and in HAM patients (27.5+/-12.1 ng/ml, P<0.0001) than in healthy individuals (4.5+/-2.1 ng/ml). High levels of AS-sIL-6R were also observed in plasma from rheumatoid arthritis patients and in persons with elevated levels of alanine aminotransferase (ALT), antinuclear antibody (ANA), or alpha-fetoprotein (AFP). However, in human immunodeficiency virus-1 (HIV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV)-infected individuals, AS-sIL-6R levels were not elevated. In this study, we confirmed that AS-sIL-6R is indeed present in human sera. These observations suggest that alternative splicing of IL-6R mRNA is of consequence in ATL, HAM and in some autoimmune diseases. The HTLV-I-infected T cells appeared to play an important role in AS-sIL-6R production.
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PMID:High-level production of alternatively spliced soluble interleukin-6 receptor in serum of patients with adult T-cell leukaemia/HTLV-I-associated myelopathy. 982 98


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