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211.
Polymorphic thiopurine methyltransferase in erythrocytes is indicative of activity in leukemic blasts from children with acute lymphoblastic leukemia 总被引:12,自引:0,他引:12
The activity of thiopurine methyltransferase (TPMT) exhibits genetic polymorphism, with approximately 1 in 300 individuals inheriting TPMT deficiency as an autosomal recessive trait, and about 11% having intermediate activity (ie, heterozygotes). Patients with TPMT deficiency accumulate excessive concentrations of 6-thioguanine nucleotides (TGNs) and develop severe toxicity when treated with standard dosages of mercaptopurine. High TPMT activity has been associated with lower concentrations of TGNs, yielding a higher risk of treatment failure in children with acute lymphoblastic leukemia (ALL). As the biochemical basis of these pharmacodynamic relationships has not been fully elucidated, we investigated the variability and relationship of TPMT activity in erythrocytes and lymphoblasts from children with ALL. A 58-fold range of erythrocyte TPMT activity was found among 119 patients receiving ALL chemotherapy (0.6 to 34.9 U/mL packed erythrocytes), but relatively low intrapatient variability (coefficient of variation, 13.5%) was observed over 1 year. A 27-fold range in TPMT activity was observed in leukemic blasts obtained from 42 patients at initial diagnosis (3.3 to 88.9 U/1 x 10(9) cells). TPMT activity in leukemic blasts at diagnosis was significantly correlated with TPMT in erythrocytes before therapy (rs = .75, P < .0001, N = 13). These data document extensive interpatient variability of TPMT activity in ALL blasts and establish its linkage to polymorphic TPMT activity in erythrocytes, providing a new mechanism by which erythrocytes serve as prognostic markers of mercaptopurine metabolism and TPMT activity in children with ALL. 相似文献
212.
Most children with congenital cystic adenomatoid malformation present in the first six months of life. Three cases are described with unusually late presentation. One child was completely asymptomatic and another became symptomatic only after secondary infection of a congenital cystic adenomatoid malformation. In two cases the correct diagnosis was not made preoperatively. The value of preoperative lung scanning was demonstrated in one case in which a lung scan showed a larger perfused area than indicated on the radiograph. At operation, a lobulated cystic structure was seen attached by a thin pedicle to the interior surface of the left upper lobe. 相似文献
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215.
Marta Scandurra Davide Rossi Clara Deambrogi Paola MV Rancoita Ekaterina Chigrinova Michael Mian Michaela Cerri Silvia Rasi Elisa Sozzi Francesco Forconi Maurilio Ponzoni Santiago M Moreno Miguel A Piris Giorgio Inghirami Emanuele Zucca Valter Gattei Andrea Rinaldi Ivo Kwee Gianluca Gaidano Francesco Bertoni 《Hematological oncology》2010,28(2):62-67
Richter's syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma and is mostly represented by diffuse large B‐cell lymphoma (DLBCL), with a post‐germinal centre (GC) phenotype, clonally related to the pre‐existing CLL. RS has a very poor prognosis and its pathogenetic mechanisms are poorly understood. In order to gain additional hints in RS pathogenesis, we performed a genome‐wide DNA profiling study of 13 RS phases and eight matched CLL phases using the Affymetrix Human Mapping 250K NspI SNP arrays. Individual genomic profiles were heterogeneous, with no individual lesions occurring in more than half of the cases. However, several observations suggest that MYC pathway might be involved in RS. The 13q13.3‐qter region containing MIRHG1 (MIR‐17‐92), a cluster of microRNA interacting with c‐MYC, was acquired at the time of transformation. The 13q gain was coupled with the gain of c‐MYC and loss of TP53. Translocation of c‐MYC was acquired at transformation in a fraction of cases and this event appeared mutually exclusive with gain of MIRHG1. MYCN, a c‐MYC homologue, was also recurrently gained. By comparing RS with 48 de novo DLBCL, RS presented a significantly lower prevalence of deletions affecting the PRDM1 and TNFAIP3, genes on 6q, known to be associated with a post‐GC phenotype. In conclusion, the genomic profile of RS seems to differ from what observed in de novo DLBCL and in other transformed DLBCL. Genomic lesions occurring in RS are heterogeneous suggesting the existence of different RS subsets, possibly due to different transforming mechanisms. A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
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Núria Aranda Fernando E. Viteri Carme Montserrat Victoria Arija 《Annals of hematology》2010,89(8):767-773
Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism
characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase
the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and
S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status,
in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated
from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2%
in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote,
H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative
to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators
of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these
levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the
indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish
Mediterranean population. 相似文献
218.
Alejandro Allepuz Mireia Espallargues Montse Moharra Mercè Comas Joan MV Pons Research Group on Support Instruments – IRYSS Network 《BMC health services research》2008,8(1):76
Background
Prioritisation instruments were developed for patients on waiting list for hip and knee arthroplasties (AI) and cataract surgery (CI). The aim of the study was to assess their convergent and discriminant validity and inter-observer reliability. 相似文献219.
Cucó G Fernandez-Ballart J Arija V Canals J 《International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ern?hrungsforschung. Journal international de vitaminologie et de nutrition》2005,75(5):320-326
The aim of this study was to analyze how micronutrient intake during preconception and pregnancy affects neonatal behavior. A total of 66 healthy women volunteers were studied during preconception and in weeks 6, 10, 26, and 38 of pregnancy using the seven-day dietary record. The behavior of the newborn infant was assessed after three days of life using the Neonatal Behavioral Assessment Scale (NBAS). Multiple linear regression models were built and adjusted for the confounding variables in each of the periods studied and for each one of the various NBAS clusters. The intake of vitamins B1 and B6 in the sixth week of pregnancy and of iron in the 38th week of pregnancy have a positive and significant effect on the motor cluster of the NBAS independently of the body mass index (BMI), preconception age, gestational age, educational level, whether the mother is a smoker, the mother's personality dimensions, and the weight and sex of the newborn. The intake of B1, B6, and iron during pregnancy might contribute to the neuromotor maturity of the newborn. 相似文献
220.
Hallinan EA Hagen TJ Bergmanis A Moore WM Jerome GM Spangler DP Stevens AM Shieh HS Manning PT Pitzele BS 《Journal of medicinal chemistry》2004,47(4):900-906
5(S)-Fluoro-N6-(iminoethyl)-l-lysine (14), an analogue of the potent, selective induced nitric oxide synthase (iNOS) inhibitor iminoethyl-l-lysine (1), was synthesized and found to be a selective iNOS inhibitor. 相似文献