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Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients

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Asian Journal of Andrology 2012年第4期14卷 580-583页

作者： Toshinobu Miyamoto Aldra Tsujimura Yasushi Miyagawa eitetsu koh Mikio Namiki Michiharu Horikawa Yasuaki Saijo Kazuo Sengoku Department of Obstetrics and Gynecology Asahikawa Medical University Asahikawa Hokkaido 078-8510 Japan Department of Urology Osaka University Graduate School of Medicine Suita 565-0871 Japan Department of Integrated Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa 920-1192 Japan Division of Community Medicine and Epidemiology Department of Health Science Asahikawa Medical University Asahikawa 078-8510 Japan

Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.

关键词： azoospermia HORMAD1 male infertility male meiosis SNP

Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism： a multicenter, randomized controlled trial in Japan （EARTH Study）

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Asian Journal of Andrology 2016年第1期18卷 25-34页

作者： Hiroyuki Konaka Kazuhiro Sugimoto Hideki Orikasa Teruaki Iwamoto Toshinari Takamura Yoshiyu Takeda Kazuyoshi Shigehara Masashi Iijima eitetsu koh Mikio Namiki Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan Division of Biostatistics and Clinical Epidemiology University of Toyama School of Medicine Toyama Toyama Japan Division of Male Infertility Center for Infertility and IVF International University of Health and Welfare Nasushiobara Tochigi Japan Department of Disease Control and Homeostasis Kanazawa University Graduate Schoofof Medical Science Kanazawa Ishikawa Japan Departrnent of Internal Medicine. Division of Endocrinology and Hypertension Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan.

Androgen replacement therapy （ART） efficacy on late-onset hypogonadism （LOH） has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores （IPSS）, International Index of Erectile Function-5 （IIEF-5） scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART （n = 169） or control groups （n = 165）. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey （SF-36） scale （P= 0.0318）. ART was also associated with significant decreases in waist circumstance （P = 0.002） and serum triglyceride （TG）（P = 0.013） and with significant increases in whole-body and leg muscle mass volumes （P= 0.071 and 0.0108, respectively）, serum hemoglobin （P 〈 0.001）, IPSS voiding subscore （P = 0.0418）, and the second question on I IEF-5 （P = 0.0049）. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.

关键词： androgen replacement therapy health-related quality of life late-onset hypogonadism randomized controlled trial testosterone

Aberrant methylation of the TDMR of the GTF2AIL promoter does not affect fertilisation rates via TESE in patients with hypospermatogenesis

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Asian Journal of Andrology 2013年第5期15卷 634-639页

作者： Kazuhiro Sugimoto eitetsu koh Masashi Iijima Masaki Taya Yuji Maeda Mikio Namiki Departments of Integrative Cancer Therapy and Urology Andrology Unit Kanazawa University Graduate School of Medical Science Takara Kanazawa 920-8641 Japan

Increasing evidence shows a relationship between epigenetic regulation and male infertility. The GTF2A1L gene promoter contains the DNA methylation site of a tissue-specific differentially methylated region （TDMR）. Eighty-six patients with non-obstructive azoospermia were assessed for the DNA methylation state of CpG islands in the GTF2AIL promoter using testicular genomic DNA. Based on histological criteria, 26 of the 86 patients had normal spermatogenesis （controls）, 17 had hypospermatogenesis and 26 had a Sertoli cell-only phenotype or tubular sclerosis. GTF2AIL TDMR methylation was significantly lower in testes DNA from control samples than from hypospermatogenic samples （P=0.029）. Patients with hypospermatogenesis were divided into two subgroups： high DNA methylation （HM, n=5） and low DNA methylation （LM, n= 12）. The GTF2AIL TDMR methylation rate differed significantly between the HM and LM groups （P=0.0019）, and GTF2A 1L expression was significantly higher among the LM than in the HM patients （P=0.023）. High TDMR methylation was correlated with low GTF2AIL gene expression levels. Both groups demonstrated relatively good outcomes with respect to sperm retrieval, fertilisation, pregnancy and childbirth rates. We observed that aberrant GTF2AIL gene expression was not correlated with fertilisation rates. The testicular sperm extraction （TESE） technique may be used to overcome male infertility due to aberrant TDMR methvlation.

关键词： ALF azoospermia CpG island hypospermatogenesis MALDI-TOF MS testicular sperm extraction (TESE)

A single nucleotide polymorphism in SPA TA17 may be a genetic risk factor for Japanese patients with meiotic arrest

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Asian Journal of Andrology 2009年第5期11卷 623-628,I0004,I0005页

作者： Toshinobu Miyamoto[日本] Akira Tsujimura[日本] Yasushi Miyagawa[日本] eitetsu koh[日本] Naoko Sakugawa[日本] Hiroe Miyakawa[日本] Hisashi Sato[日本] Mikio Namiki[日本] Akihiko Okuyama[日本] Kazuo Sengoku[日本] Department of Obstetrics and Gynecology Asahikawa Medical College Asahikawa Hokkaido 078-851 O Japan＂ Department of Urology Graduate School of Medicine Osaka University Suita 565-0871 Japan＂ Department of Integrated Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa920-8641 Japan

Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis were identified by microarray analysis of human testicular tissue. One of these is spermatogenesis-associated 17 （SPATA17）. To investigate whether defects in the SPATA17 gene are associated with azoospermia due to meiotic arrest, a mutational analysis was conducted, in which the SPATA17 coding regions of 18 Japanese patients with this condition were sequenced. A statistical analysis was carried out that included 18 patients with meiotic arrest, 20 patients with Sertoli-cell-only syndrome （SCOS） and 96 healthy control men. No mutations were found in SPA TA17. However, three coding single nucleotide polymorphisms （cSNPs： SNP 1-SNP3） were detected in the patients with meiotic arrest. No significant differences in the genotype or allele frequencies of SNP1 and SNP2 were found between patients with meiotic arrest and the others. However, the frequency of the SNP3 allele was significantly elevated in the meiotic arrest group （P 〈 0.05）. This study suggests that SPATA17 may play a critical role in human spermatogenesis, especially in meiosis.

关键词： azoospermia meiosis polymorphism SNP SPATA17

Preoperative Exercise Testing Is a Better Predictor of Postoperative Complications than Pulmonary Function Testing for Patients with Lung Cancer

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Open Journal of Thoracic Surgery 2015年第1期5卷 15-20页

作者： Atsushi Hata Yasuo Sekine eitetsu koh Nobuyuki Yamaguchi Department of Thoracic Surgery Tokyo Women’s Medical University Yachiyo Medical Center Yachiyo Japan Division of Clinical Physiology Tokyo Women’s Medical University Yachiyo Medical Center Yachiyo Japan

Objective: The aim of this preliminary study was to evaluate the feasibility of exercise testing (ET) for predicting postoperative complications in patients with impaired pulmonary function. Methods: Thirteen patients were prospectively enrolled. The enrollment criteria were FEV1.0% 8 by the Goddard classification or interstitial pneumonia on chest computed tomography. Patients underwent testing for pulmonary function, six-minute walking test (6MWT), and stair-climbing test (SCT). Postoperative cardiopulmonary complications (PCPCs) were recorded. Results: Four patients developed PCPCs. There were no significant differences between the patients with PCPCs (n = 4) and those without PCPCs (n = 9) for background data and PFT. The distances achieved in the 6MWT were 503 ± 72.7 m for patients without PCPCs and 369 ± 50.7 m for patients with PCPCs (p = 0.011). The SCT climbing heights were 20.4 ± 5.3 m for patients without PCPCs and 14.9 ± 4.0 m for patients with PCPCs (P = 0.187). Cut-off points, including a 6MFT distance of less than 400 m, SCT height lower than 15 m, and SCT climbing speed less than 8.5 m/min, were predictive of CPCP. Conclusions: Exercise testing is more feasible for predicting postoperative cardiopulmonary complications than stationary pulmonary function testing.

关键词： Lung Cancer Exercise Testing Postoperative Complication Pulmonary Function Testing

High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

Examples of entropy generating sequence

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Science China Mathematics 2011年第3期54卷 531-538页

作者： PARK Kyewon koh Department of Mathematics Ajou University

We introduce the notion of entropy generating sequence for infinite words and define its dimension when it exists. We construct an entropy generating sequence for each symbolic example constructed by Cassaigne such that the dimension of the sequence is the same as its topological entropy dimension. Hence the complexity can be measured via the dimension of an entropy generating sequence. Moreover, we construct a weakly mixing example with subexponential growth rate.

关键词： entropy dimension entropy generating sequence complexity

Perfusion magnetic resonance imaging of the liver

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World Journal of Gastroenterology 2010年第13期16卷 1598-1609页

作者： Choon Hua Thng Tong San koh David J Collins Dow Mu koh Department of Oncologic Imaging National Cancer Centre Department of Radiology Royal Marsden NHS Foundation Trust CR UK-EPSRC Cancer Imaging Centre Institute of Cancer Research

Perfusion magnetic resonance imaging (MRI) studies quantify the microcirculatory status of liver parenchyma and liver lesions, and can be used for the detection of liver metastases, assessing the effectiveness of antiangiogenic therapy, evaluating tumor viability after anticancer therapy or ablation, and diagnosis of liver cirrhosis and its severity. In this review, we discuss the basic concepts of perfusion MRI using tracer kinetic modeling, the common kinetic models applied for analyses, the MR scanning techniques, methods of data processing, and evidence that supports its use from published clinical and research studies. Technical standardization and further studies will help to establish and validate perfusion MRI as a clinical imaging modality.

关键词： Magnetic resonance imaging Dynamic contrast-enhanced magnetic resonance imaging Liver Tracer kinetic modeling

Comparison of intraocular pressure peak and fluctuations among Filipino patients with non-glaucomatous eyes and glaucoma suspects using water drinking test and diurnal intraocular pressure

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International Journal of Ophthalmology(English edition) 2021年第11期14卷 1729-1734页

作者： Anelisa koh Cynthia Verzosa Department of Ophthalmology Jose R.Reyes Memorial Medical CenterManila 1003Philippines

AIM:To compare the intraocular pressure(IOP)peaks and fluctuations using water drinking tests(WDTs)and mean diurnal IOP among Filipino patients with normal eyes and glaucoma suspectsMETHODS:This prospective study included normal and glaucoma suspect *** patient underwent both WDT and mean diurnal examination on separate *** mean diurnal examination,IOP was recorded every 2 h for 8 h while in WDT,IOP was recorded prior to WDT,and postWDT at 5,15,30,45,and 60 *** peak was recorded as the highest IOP for both methods,and IOP fluctuation was recorded as highest IOP minus lowest ***:With the comparison of diagnostic tests,both normal eyes and glaucoma suspect groups,the peak IOP was caught at 15 *** analysis of both groups also showed that the peak IOP measurements were statistically higher for the WDT compared to mean diurnal IOP(P=0.039,P=0.048 under normal group and P=0.032 and P=0.031 under glaucoma suspect group).Similarly,the WDT had a statistically higher mean IOP fluctuation score than the mean diurnal IOP method in both groups(P=0.003,P=0.011 under normal group;P=0.002 and P=0.005 under glaucoma suspect group).CONCLUSION:This study shows that WDT is a comparable diagnostic exam in predicting IOP fluctuations than mean diurnal *** is a promising diagnostic procedure for risk assessment in glaucoma.

关键词： glaucoma waterdrinking test intraocular pressure intraocular pressure peak fluctuation