22 research outputs found

    漢方薬とそれを構成する生薬のインフルエンザウイルス増殖に対する影響 : カンゾウによるウイルス蛋白質合成抑制

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    広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

    Evaluation of sample size effect on the identification of haplotype blocks

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    Background: Genome-wide maps of linkage disequilibrium (LD) and haplotypes have been created for different populations. Substantial sharing of the boundaries and haplotypes among populations was observed, but haplotype variations have also been reported across populations. Conflicting observations on the extent and distribution of haplotypes require careful examination. The mechanisms that shape haplotypes have not been fully explored, although the effect of sample size has been implicated. We present a close examination of the effect of sample size on haplotype blocks using an original computational simulation. Results: A region spanning 19.31 Mb on chromosome 20q was genotyped for 1,147 SNPs in 725 Japanese subjects. One region of 445 kb exhibiting a single strong LD value (average |D'|; 0.94) was selected for the analysis of sample size effect on haplotype structure. Three different block definitions (recombination-based, LD-based, and diversity-based) were exploited to create simulations for block identification with θ value from real genotyping data. As a result, it was quite difficult to estimate a haplotype block for data with less than 200 samples. Attainment of a reliable haplotype structure with 50 samples was not possible, although the simulation was repeated 10,000 times. Conclusion: These analyses underscored the difficulties of estimating haplotype blocks. To acquire a reliable result, it would be necessary to increase sample size more than 725 and to repeat the simulation 3,000 times. Even in one genomic region showing a high LD value, the haplotype block might be fragile. We emphasize the importance of applying careful confidence measures when using the estimated haplotype structure in biomedical research

    Evaluation of sample size effect on the identification of haplotype blocks

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    <p>Abstract</p> <p>Background</p> <p>Genome-wide maps of linkage disequilibrium (LD) and haplotypes have been created for different populations. Substantial sharing of the boundaries and haplotypes among populations was observed, but haplotype variations have also been reported across populations. Conflicting observations on the extent and distribution of haplotypes require careful examination. The mechanisms that shape haplotypes have not been fully explored, although the effect of sample size has been implicated. We present a close examination of the effect of sample size on haplotype blocks using an original computational simulation.</p> <p>Results</p> <p>A region spanning 19.31 Mb on chromosome 20q was genotyped for 1,147 SNPs in 725 Japanese subjects. One region of 445 kb exhibiting a single strong LD value (average |D'|; 0.94) was selected for the analysis of sample size effect on haplotype structure. Three different block definitions (recombination-based, LD-based, and diversity-based) were exploited to create simulations for block identification with <it>θ </it>value from real genotyping data. As a result, it was quite difficult to estimate a haplotype block for data with less than 200 samples. Attainment of a reliable haplotype structure with 50 samples was not possible, although the simulation was repeated 10,000 times.</p> <p>Conclusion</p> <p>These analyses underscored the difficulties of estimating haplotype blocks. To acquire a reliable result, it would be necessary to increase sample size more than 725 and to repeat the simulation 3,000 times. Even in one genomic region showing a high LD value, the haplotype block might be fragile. We emphasize the importance of applying careful confidence measures when using the estimated haplotype structure in biomedical research.</p

    Inactivation of the Influenza Virus by a Supplemental Fermented Plant Product (Manda Koso)

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    Manda Koso is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that are fermented for more than 3 years. We hypothesized that the FPP can prevent infection by influenza virus and human norovirus. Therefore, we investigated the effects of the FPP on influenza virus and feline calicivirus, a surrogate of human norovirus. We found that 10% FPP inactivated the influenza virus but not the feline calicivirus. Inhibition of the influenza virus was highly concentration-dependent: 1% and 0.3% FPP showed reduced inactivation efficacy. The effects of the FPP on the influenza virus-infected cells were investigated by addition of the FPP to the culture medium after virus infection. No suppressive effect of the FPP on influenza replication in MDCK cells was observed. The results showed that the FPP could inactivate influenza virus by affecting the virus particles

    Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population

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    Background: Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between D15S118 and D15S117 in a Japanese population using a region-wide case-control association test. Methods: A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed. Results: SNP2140 (rs2412747) (C/T) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal p value (p = 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07–1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing. Conclusion: The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations

    Accuracy management survey of nucleic acid amplification tests using inactivated SARS-CoV-2 in Hiroshima Prefecture

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    At the beginning of 2020, the number of laboratories performing SARS-CoV-2 testing increased with the rapid expansion of COVID-19 in Hiroshima Prefecture. Thus, it is necessary to compare and verify the validity of the test results among local laboratories. In this study, we distributed the same standard samples to laboratories that performed COVID-19 testing using the nucleic acid amplification method and confirmed the accuracy of the tests. The SARS-CoV-2 strain distributed by the National Institute of Infectious Diseases (NIID), Japan, was used for testing. As measured by RT-qPCR, a specific amount of the virus was inactivated by ethanol and dried as specimens for distribution. This study included 27 tests performed at 15 laboratories conducting or planning to conduct nucleic acid amplification tests (RT-qPCR and LAMP methods) for SARSCoV-2. The detection limit of each test method was set at the value provided by the NIID. The accuracy of the tests was examined to determine whether they met the required accuracy criteria. SARS-CoV-2 genomic RNA was reliably detected in all 27 tests. The inactivated specimens used in this study were safe to distribute and could be used as positive controls for all methods.This study was supported by a grant from the Government-Academia Collaboration of Hiroshima Prefecture and by a research grant for COVID-19 from AMED, Japan under Grant Number 20he0622011h0001(to J. T.)

    Antimicrobial Resistance of Breakthrough-Urinary Tract Infections in Children under Antimicrobial Prophylaxis

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    Antimicrobial prophylaxis using cefaclor or trimethoprim-sulfamethoxazole (co-trimoxazole) is recommended for children with vesicoureteral reflex (VUR) to prevent recurrent urinary tract infection (UTI). This retrospective study was performed by reviewing the data of children ≥5 years of age treated for recurrent UTI in six hospitals from 2010 to 2015. The criteria for UTI diagnosis is fever (≥38°C) and positive results in urine culture (>104 colony-forming units/ml in midstream or withdrawn urine specimens). In total, 41 children were reviewed, and 31 children had recurrent UTI without antimicrobial prophylaxis and 10 had breakthrough (BT)-UTI treated with prophylaxis using cefaclor or co-trimoxazole. In the cases of BT-UTI treated with prophylaxis, 5 children received cefaclor and 5 received co-trimoxazole. We collected data on pathogens, antimicrobial resistance, and antimicrobial agents chosen for the empirical treatment of recurrent UTI. We also evaluated the validity of empirical therapy for recurrent UTI in this study. Various pathogens were found in children who received prophylaxis with cefaclor. The rate of empirical antimicrobial agents that were inappropriate based on antimicrobial susceptibility tests was higher in children who received prophylaxis with cefaclor (60.0%) than in those who received no prophylaxis (25.9%) or prophylaxis with co-trimoxazole (20.0%). Prophylaxis with cefaclor was found to be a risk factor for inappropriate empirical treatment in BT-UTI cases. The results suggest that the choice of empirical antimicrobial agents in BT-UTI cases should be carefully considered before treatment with prophylaxis. To encourage the adequate use of antimicrobial agents, we recommend prophylaxis with co-trimoxazole to prevent recurrent UTI

    Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population

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    <p>Abstract</p> <p>Background</p> <p>Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between <it>D15S118 </it>and <it>D15S117 </it>in a Japanese population using a region-wide case-control association test.</p> <p>Methods</p> <p>A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed.</p> <p>Results</p> <p>SNP2140 (rs2412747) (<it>C/T</it>) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (<it>UBR1</it>) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal <it>p </it>value (<it>p </it>= 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07–1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing.</p> <p>Conclusion</p> <p>The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.</p
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