DSpace community: 醫學檢驗暨生物技術學系

Hla-Dpb1*0201 Allele Is Negatively Associated with Immunoglobulin E Responsiveness Specific for House Dust Mite Allergens in Taiwan

title: Hla-Dpb1*0201 Allele Is Negatively Associated with Immunoglobulin E Responsiveness Specific for House Dust Mite Allergens in Taiwan abstract: Background: House dust mite (HDM) Dermatophagoides pteronyssinus (Dp) is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p1, Der p2 and Der p5) to detect allergen-specific IgE responsiveness among large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM. Objective: This study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, Dp. Method: Two hundred and forty-eight subjects were selected for HLA association study. Plasma HDM allergens (Der p1, Der p2, Der p5)- specific IgE and Der p2-specific IgG antibodies were detected by ELISA, while HLA class II -DRB1, -DQA1, -DQB1, - DPB1 genetic polymorphism was determined by polymerase chain reaction / sequence-specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergens-specific IgE and IgG antibodies were performed . Results: There was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM- specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p5- specific IgE responsiveness. However, we found that HLA-DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p1 and Der p5 . There was a strong negative association between the HLA-DPB1*0201 allele with IgE responsiveness to Der p1 (OR: 0.30, p<0.0001, p<0.0007, pc<0.010 ). Conclusion: We clearly observed the association between HLA DPB1 alleles and specific IgE responsiveness to HDM major allergens. The molecular mechanism of HLA-DPB1* 0201 involvement in protecting subjects from HDM-specific IgE responsiveness await further investigation.

Ganoderic Acid X, a Lanostanoid Triterpene, Inhibits Topoisomerases and Induces Apoptosis of Cancer Cells

title: Ganoderic Acid X, a Lanostanoid Triterpene, Inhibits Topoisomerases and Induces Apoptosis of Cancer Cells abstract: Lanostanoid triterpenes isolated from Ganoderma amboinense were found to inhibit the growth of numerous cancer cell lines, and some of them inhibited the activities of topoisomerases I and II?? in vitro. Among the bioactive isolates, one of the most potent triterpene was identified to be 3??-hydroxy-15??-acetoxy-lanosta-7,9(11),24-trien-26- oic acid, ganoderic acid X (GAX). Treatment of human hepatoma HuH-7 cells with GAX caused immediate inhibition of DNA synthesis as well as activation of ERK and JNK mitogen- activated protein kinases, and cell apoptosis. Molecular events of apoptosis including degradation of chromosomal DNA , decrease in the level of Bcl-xL, the disruption of mitochondrial membrane, cytosolic release of cytochrome c and activation of caspase-3 were elucidated. The ability of GAX to inhibit topoisomerases and to sensitize the cancer cells toward apoptosis fulfills the feature of a potential anticancer drug.

Regulatory Roles of Spnt, a Novel Gene Located within Transposon Tntir

title: Regulatory Roles of Spnt, a Novel Gene Located within Transposon Tntir abstract: The transposon TnTIR contains spnIR quorum-sensing system regulating sliding motility and the production of nuclease, biosurfactant, and prodigiosin in Serratia marcescens. Within TnTIR, a gene named spnT is upstream of and co- transcribed with spnI SpnT is a cytoplasmic protein and its level peaks during early stationary phase. spnT over- expression resulted in inhibition of sliding motility and synthesis of prodigiosin, and biosurfactant similar to spnR. spnT but not spnR over-expression induced cell elongation and aberrant DNA replication in S. marcescens and Escherichia coli strains. In comparison with wild-type E coli strain, over -expression of spnT in an E coli priA and dnaC double-mutant strain did not lead to the aberrant cell morphology phenotypes, suggesting SpnT may act through the recombination-dependent DNA replication system. As spnT over -expression inhibited swarming but not swimming motility, SpnT may indirectly function as a negative regulator of surface-dependent migration and secondary metabolite production. (c) 2006 Elsevier Inc. All rights reserved.

A Two-Stage Design for Multiple Testing in Large-Scale Association Studies

title: A Two-Stage Design for Multiple Testing in Large-Scale Association Studies abstract: Modern association studies often involve a large number of markers and hence may encounter the problem of testing multiple hypotheses. Traditional procedures are usually over -conservative and with low power to detect mild genetic effects. From the design perspective, we propose a two-stage selection procedure to address this concern. Our main principle is to reduce the total number of tests by removing clearly unassociated markers in the first-stage test. Next, conditional on the findings of the first stage, which uses a less stringent nominal level, a more conservative test is conducted in the second stage using the augmented data and the data from the first stage. Previous studies have suggested using independent samples to avoid inflated errors . However, we found that, after accounting for the dependence between these two samples, the true discovery rate increases substantially. In addition, the cost of genotyping can be greatly reduced via this approach. Results from a study of hypertriglyceridemia and simulations suggest the two-stage method has a higher overall true positive rate (TPR) with a controlled overall false positive rate (FPR) when compared with single-stage approaches. We also report the analytical form of its overall FPR, which may be useful in guiding study design to achieve a high TPR while retaining the desired FPR .