Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polymerase chain reaction with prior reverse transcription of RNA into cDNA was applied to hepatitis C virus RNA detection in human serum samples of different origin. In order to eliminate false negative results, the following steps were optimized: RNA extraction, reverse transcription, and oligonucleotide primer selection. We compared different RNA extraction methods using guanidinium salt/detergent and proteinase K digestion/phenol extraction, and tested virus particle enrichment with polyethylene glycol precipitation and ultracentrifugation. RNA extraction with guanidinium salt/detergent was the most efficient method. Ultracentrifugation of single samples did not improve hepatitis C virus RNA detection. Polyethylene glycol precipitation performed poorly. Recombinant thermostable reverse transcriptase produced cDNA from fewer samples than did Moloney murine leukaemia virus reverse transcriptase. Nested oligonucleotide primers from the 5'-terminal non-coding region of the hepatitis C virus genome amplified cDNA from more samples than did primers from the coding regions. Thirty six anti-hepatitis C virus antibody positive samples were tested; nested primers (nucleotides 6 to 327 and 15 to 288) yielded 21 amplificates, whereas primers from the coding region produced 16 amplificates (nucleotides 4684-5276) and 5 amplificates (nucleotides 5166-5270), respectively. The most efficient combination of steps was RNA extraction with guanidinium salt solution, reverse transcription with Moloney murine leukaemia virus reverse transcriptase and nested polymerase chain reaction primed with primers from the 5'-terminal non-coding region of the hepatitis C virus genome. Other combinations produced more false negative results. Three different groups of anti-hepatitis C virus antibody positive individuals had markedly different viraemia patterns: Hepatitis C virus RNA was detected in the sera of only 10% of anti-hepatitis C virus antibody positive blood donors, but in 90% of anti-hepatitis C virus antibody positive patients with clinically manifest hepatitis C, and 90% of anti-hepatitis C virus antibody positive haemophiliacs who had received plasma products in the past which had not been virus-inactivated. No hepatitis C virus RNA could be detected in the sera of 450 anti-hepatitis C virus antibody negative blood donors with elevated serum alanine aminotransferase catalytic concentrations.
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PMID:Improved detection of hepatitis C virus RNA by reverse transcription and polymerase chain reaction. 128 41

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.
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PMID:Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus. 168 26

Determining the current status of therapeutic results of acute lymphoblastic leukemia (ALL), and identifying the important clinical predictors of survival and relapse are essential for establishing therapeutic strategies. Sixty-two children with ALL who were admitted to Chonnam University Hospital from January 1983 to June 1991 were studied. With a mean follow-up period of 53.7 months, the overall 5-year survival rate (5YSR) was 46.1%. The overall rate of 5-year event-free survival (EFS) was 25.4% and significantly differed between risk groups: 48.7% for standard, 16.3% for high, and 12.5% for very high (p < .05). Overall 4-year survival after initial relapse was 34.2% and there was no significant difference in survival between those who relapsed during maintenance therapy and those who relapsed after completing maintenance. The Cox proportional hazards model identified central nervous system (CNS) irradiation (P < 0.001) as having the most important influence upon EFS, followed by serum alanine aminotransferase level, platelet level, and age. On the other hand, CNS leukemia at diagnosis, followed by mediastinal mass, and hemoglobin level were found to be the most important prognostic predictors for relapse. On the basis that present results differ from those of developed countries, we suggest the necessity of a nation-wide cohort study to delineate the characteristics of Korean ALL in children, to make our own protocols, and ultimately to improve the therapeutic outcome.
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PMID:Therapeutic results and prognostic predictors of childhood acute lymphoblastic leukemia: Cox regression analysis. 184 44

We studied 145 children with acute lymphocytic leukemia (ALL) in remission who had been off chemotherapy for at least 2 years, to assess the prevalence of hepatitis delta virus (HDV) infection, and to determine whether HDV infection was associated with more severe chronic liver disease. The prevalence of chronic HBV infection was 41.5% (60/145). The prevalence of HDV infection among these patients with chronic HBV infection was 50% (30/60). Eighty-five patients were HBsAg-negative. There was evidence that HDV-infected children had more severe chronic liver disease than did HBsAg-positive, anti-HDV-negative patients: (1) their serum ALT levels were significantly more likely to be elevated at long-term follow-up (27/30 vs. 10/26, p = 0.0001); (2) their mean ALT levels were significantly higher 3 years after the cessation of chemotherapy (128 vs. 84 IU/L, p = 0.001); and (3) they were more likely to have either chronic acute hepatitis or cirrhosis when liver biopsy was done (18/23 vs. 6/18, p = 0.0038). Children who were HBsAg-negative had the lowest alanine aminotransferase (ALT) levels and were least likely to have chronic active hepatitis or cirrhosis (3/31). We conclude that infection with HDV in children with ALL is associated with serious chronic liver disease. In long-term survivors, HDV infection is a major cause of morbidity and an adverse prognostic factor in terms of leukemia-free survival.
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PMID:Delta virus and childhood leukemia. 202 65

In 34 patients (16 women and 18 men) with acute leukaemias (8 with acute lymphoblastic leukaemia and 26 with acute myeloblastic leukaemia), as yet untreated, the serum levels were determined of conjugated cholic acid, bilirubin, aspartate aminotransferase (AspAT), alanine aminotransferase (AlAT), alkaline phosphatase (AP), lactate dehydrogenase (LDH) and cholinesterase (Chol). Serum conjugated cholic acid level was determined by radioimmunoassay. The mean values of AP and Chol activity were within the range of normal values in this laboratory, the values of AspAT and AlAT were slightly above this range, and LDH value exceeded twice this normal range. The mean bilirubin concentration was within normal range. The greatest changes were noted in conjugated cholic acid values, the mean value exceeded five times the upper normal range (1.0 mumol/l). In 30 patients (88%) the conjugated cholic acid level in the serum was above 1.0 mumol/l, in the remaining 4 cases it was above the mean value for the control group. No correlation was found between conjugated cholic acid and any of the determined parameters. These results point out that the serum level of conjugated cholic acid may be a valuable parameter for assessment of hepatocellular function in acute leukaemias.
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PMID:[Serum cholic acid levels in patients with acute leukemia]. 225 Dec 7

Serum biochemical analyses were done on F344 rats in the early and late stages of mononuclear cell leukemia. There were marked increases in serum bilirubin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase. Increases in these parameters generally were more severe in the late stages of leukemia. Both direct and indirect-reacting bilirubin were increased with the unconjugated form predominating early and the conjugated form predominating late in the course of the disease. Lactate dehydrogenase isoenzyme determination correlated with histological examination indicated that liver damage was responsible for the observed changes. Urinalysis revealed marked hemoglobinuria, bilirubinuria and increased urine urobilinogen. Serum protein electrophoresis revealed marked reductions in the alpha globulin fractions.
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PMID:Pathology of the mononuclear cell leukemia of Fischer rats. III. Clinical chemistry. 664 40

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

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

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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