A recent study identified a variant of the NUDT15 gene (rs116855232 C>T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A>G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mg m, 30.7 mg m and 44.1 mg m, respectively. The outcomes did not differ significantly among the different genotypes.

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Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L-and V-type PML-RARa, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.

Borna disease virus (BDV), a negative-strand RNA virus, has been reported to be associated with severe psychiatric disorders. The association is mainly based on the findings that patients with schizophrenia and depression have a higher seroprevalence rate of BDV-specific antibodies than controls. In addition, psychiatric patients were also found to have a higher detection rate of BDV transcripts in their blood than controls. By using an improved Western blot analysis, we first demonstrated that Chinese schizophrenic patients from Taiwan also have a higher seroprevalence of BDV-specific antibodies than controls (12.1% vs 2.9%, P Ͻ 0.001), providing support to the positive association between BDV and psychiatric disorders in our population. Because of the contagious nature of viral infection, we further examined patients' family members and mental health workers, who have close contact with patients. We found that both groups also have a higher seroprevalence of BDV-specific antibodies, 12.1% and 9.8%, respectively, than controls. This finding provides some evidence for a possible human-to-human transmission of Borna disease virus. Our finding needs further independent verification from other research groups and the clinical relevance of this preliminary observation deserves further study.

Intersubband lasing at 12-16 microm based on a CO2 laser pumped stimulated resonant Raman process in GaAs/AlGaAs three-level double-quantum-well structures is reported. The presence, or lack of, lasing action provides evidence for resonantly coupled modes of collective electronic intersubband transitions and longitudinal optical phonons. An anticrossing behavior of these modes is clearly seen when the difference between the pump and lasing energies (i.e., Stokes Raman shift) is compared with the subband separation. This work reveals the significance of the strong coupling between intersubband transitions and phonons and raises a new possibility of realizing a phonon "laser."

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The aim of this study was to investigate whether maternal dietary supplementations with different zinc (Zn) sources could reduce the deleterious effect of maternal heat stress on hatchability performance and progeny growth performance. A completely randomized design (n = 6) with 2 maternal environmental temperatures [normal 21 ± 1°C (NT) vs. high 32 ± 1°C (HT)] × 3 maternal dietary supplemental Zn levels [Zn-unsupplemented control diet (CON), the control diet + 110 mg of Zn/kg of diet as either inorganic ZnSO4 (iZn) or organic Zn with a moderate chelation strength (oZn)] was used. HT decreased (P < 0.05) fertility, hatchability, chick hatch weight, and embryonic survival. HT also decreased (P ≤ 0.05) progeny BW, ADG, and ADFI at one to 21, 22 to 28, and 29 to 42 d of age as well as breast muscle ratio and plasma aspartate aminotransferase and creatine kinase activities at 42 d of age. Maternal dietary Zn supplementation with either iZn or oZn increased (P < 0.004) Zn contents in yolk and liver, non-weak chick ratio, as well as progeny BW, ADFI, and survivability at one to 21 d of age. Notably, the addition of oZn increased (P < 0.05) hatchability and progeny thigh meat quality by reducing b* value. The progeny ADG at one to 21 d and 22 to 28 d of age and BW at 28 d of age from maternal NT were not affected (P > 0.46) by maternal dietary Zn supplementation, but the above 3 indices from HT-iZn (P < 0.05) and HT-oZn (P < 0.003) were higher than those from HT-CON. Our results indicate that maternal heat stress impairs hatching performance, embryonic development, and progeny growth performance, inducing metabolic changes, while supplementation of Zn in maternal diets regardless of Zn sources improved hatch chick quality and survivability of offspring and alleviated the negative effect of maternal heat stress on growth performance of offspring during the starter period. In addition, maternal dietary supplementation with the organic Zn improved hatchability and progeny meat quality.

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