A Genome-Wide Association Analysis Identified a Novel Susceptible Locus for Pathological Myopia at 11q24.1

Myopia is one of the most common ocular disorders worldwide. Pathological myopia, also called high myopia, comprises 1% to 5% of the general population and is one of the leading causes of legal blindness in developed countries. To identify genetic determinants associated with pathological myopia in Japanese, we conducted a genome-wide association study, analyzing 411,777 SNPs with 830 cases and 1,911 general population controls in a two-stage design (297 cases and 934 controls in the first stage and 533 cases and 977 controls in the second stage). We selected 22 SNPs that showed P-values smaller than 10−4 in the first stage and tested them for association in the second stage. The meta-analysis combining the first and second stages identified an SNP, rs577948, at chromosome 11q24.1, which was associated with the disease (P = 2.22×10−7 and OR of 1.37 with 95% confidence interval: 1.21–1.54). Two genes, BLID and LOC399959, were identified within a 200-kb DNA encompassing rs577948. RT–PCR analysis demonstrated that both genes were expressed in human retinal tissue. Our results strongly suggest that the region at 11q24.1 is a novel susceptibility locus for pathological myopia in Japanese

Association between the SERPING1 Gene and Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Japanese

PURPOSE: Recently, a complement component 1 inhibitor (SERPING1) gene polymorphism was identified as a novel risk factor for age-related macular degeneration (AMD) in Caucasians. We aimed to investigate whether variations in SERPING1 are associated with typical AMD or with polypoidal choroidal vasculopathy (PCV) in a Japanese population. METHODS: We performed a case-control study in a group of Japanese patients with typical AMD (n = 401) or PCV (n = 510) and in 2 independent control groups--336 cataract patients without age-related maculopathy and 1,194 healthy Japanese individuals. Differences in the observed genotypic distribution between the case and control groups were tested using chi-square test for trend. Age and gender were adjusted using logistic regression analysis. RESULTS: We targeted rs2511989 as the haplotype-tagging single nucleotide polymorphism (SNP) for the SERPING1 gene, which was reported to be associated with the risk of AMD in Caucasians. Although we compared the genotypic distributions of rs2511989 in typical AMD and PCV patients against 2 independent control groups (cataract patients and healthy Japanese individuals), SERPING1 rs2511989 was not significantly associated with typical AMD (P = 0.932 and 0.513, respectively) or PCV (P = 0.505 and 0.141, respectively). After correction for age and gender differences based on a logistic regression model, the difference in genotypic distributions remained insignificant (P>0.05). Our sample size had a statistical power of more than 90% to detect an association of a risk allele with an odds ratio reported in the original studies for rs2511989 for developing AMD. CONCLUSIONS: In the present study, we could not replicate the reported association between SERPING1 and either neovascular AMD or PCV in a Japanese population; thus, the results suggest that SERPING1 does not play a significant role in the risk of developing AMD or PCV in Japanese

Effects of ferric citrate on intracellular oxidative stress markers after hydrogen peroxide treatment of human U937 monocytes

Phosphate binders, such as iron （III） citrate hydrate （FCH）, are essential medications for hemodialysis patients. Some in vivo studies have demonstrated that FCH prevented induction of oxidative stress in the presence of transferrin. However, how FCH affects iron-related oxidative stress in the absence of transferrin remains unclear. In the current study, we investigated the effects of ferric citrate （FC） on oxidative stress in the absence of transferrin in vitro to address this question. Human U937 monocytes were pretreated with FC, iron （II） chloride tetrahydrate （FeCl2・4H2O）, iron （III） chloride hexahydrate （FeCl3・6H2O）, or saccharated ferric oxide for 24 h and then treated with 10-mM hydrogen peroxide （H2O2） for 30 min. The final Fe concentrations were adjusted to approximately 200µg/dl. Iron concentration, intracellular reactive oxygen species （ROS） levels, and intracellular lipid peroxidation of the cell membrane were measured. After treatment with FC, iron concentration and ROS levels increased. Change in lipid peroxidation after treatment with FC was not observed. However, after treatment with H2O2, no change was observed in the intracellular ROS levels in FC-pretreated cells, whereas lipid peroxidation of the cell membrane was decreased. Despite the high iron concentration in FC-pretreated cells, neither intracellular ROS nor cell membrane lipid peroxidation levels were increased with H2O2 treatment. Their results might represent antioxidative effects of FC. The results of this study may contribute to a better understanding of the effects of oxidative stress in hemodialysis patients treated with FCH

Management of prenatal ovarian cysts

Objectives: The aim of the present study was to analyze the antenatal and postnatal outcome of fetal ovarian cysts in relation to their ultrasonographic pattern and size. Methods: Sixteen fetal ovarian cysts were diagnosed in 16 fetuses and followed with serial ultrasonograms in utero and after birth until spontaneous or surgical resolution. Results: Eleven fetal ovarian cysts were simple cysts at first prenatal scan but 3 of the 11 became complex cysts at last prenatal scan and required postnatal laparoscopic surgery. Seven of the 11 simple cysts (63%) disappeared on follow up imaging by ultrasonograms or MRI during pregnancy or within 2 months after birth. The rate of spontaneous resolution of simple cysts was higher than that of complex cysts (40.0%). The mean maximum diameter of the ovarian cysts before delivery that were subsequently excised surgically at postnatal period (50±13.4 mm) was not different from that of ovarian cysts that resolved spontaneously (42.8±12.8 mm, P= 0.2918).Conclusion: In our study, cyst size did not predict the risk of ovarian loss. The opportunity of laparoscopic exploration versus conservative management needs to be investigated because some complex cysts resolved spontaneously in the postnatal period

The Origin and Genetic Variation of Domestic Chickens with Special Reference to Junglefowls Gallus g. gallus and G. varius

It is postulated that chickens (Gallus gallus domesticus) became domesticated from wild junglefowls in Southeast Asia nearly 10,000 years ago. Based on 19 individual samples covering various chicken breeds, red junglefowl (G. g. gallus), and green junglefowl (G. varius), we address the origin of domestic chickens, the relative roles of ancestral polymorphisms and introgression, and the effects of artificial selection on the domestic chicken genome. DNA sequences from 30 introns at 25 nuclear loci are determined for both diploid chromosomes from a majority of samples. The phylogenetic analysis shows that the DNA sequences of chickens, red and green junglefowls formed reciprocally monophyletic clusters. The Markov chain Monte Carlo simulation further reveals that domestic chickens diverged from red junglefowl 58,000±16,000 years ago, well before the archeological dating of domestication, and that their common ancestor in turn diverged from green junglefowl 3.6 million years ago. Several shared haplotypes nonetheless found between green junglefowl and chickens are attributed to recent unidirectional introgression of chickens into green junglefowl. Shared haplotypes are more frequently found between red junglefowl and chickens, which are attributed to both introgression and ancestral polymorphisms. Within each chicken breed, there is an excess of homozygosity, but there is no significant reduction in the nucleotide diversity. Phenotypic modifications of chicken breeds as a result of artificial selection appear to stem from ancestral polymorphisms at a limited number of genetic loci

停留精巣の研究 第3報: 停留精巣患者における精巣内複合糖質の組織化学的研究

3～37歳の停留精巣患者23例の停留精巣および対側陰嚢内精巣において, 光顕組織化学的方法にて複合糖質の変化を観察し, さらに正常精巣組織と比較した.停留精巣精細管壁及び間質では, 正常精巣に比べ酸性ムコ多糖(精細管壁:コンドロイチン硫酸A及びC, 間質:コンドロイチン硫酸B)が減少し, 特に精細管壁において顕著であった.なお, 患側精細管上皮においては, 思春期前から思春期以後を通じ, グリコーゲン及びガラクトース含有量の減少が認められたThe complex carbohydrates in the undescended and contralateral scrotal testes of patients with cryptorchidism, were examined by light microscopic histochemical methods, in comparison with those of normal testes. In the undescended testes, histochemical reactions for acidic and neutral complex carbohydrates were apparently weaker than in the normal testes, especially pronounced in the seminiferous tubular walls. In the germinal and supporting cells of the undescended testes, the amount of galactose residues in the complex carbohydrates decreased from the prepubertal to post-pubertal periods. Periodic acid-Schiff reaction also revealed a decrease in the glycogen content in the germinal and supporting cells of the undescended testes from pre-pubertal to post-pubertal periods

膀胱内Inverted Papillomaの2例

膀胱内に発生したInvertedPapiliomaの2例を報告し, 若干の文献的考察を加えた.患者はそれぞれ肉眼的血尿と尿線途絶を主訴とする39歳の男性と36歳の女性であった.両症例とも膀胱内腫瘍は経尿道的に切除され, 組織学的ecPt型的なInvertedPapillomaの所見を示した.Two cases of inverted papilloma of the urinary bladder are reported. The patients were a 39-year-old male with macrohematuria and a 36-year-old female with interrupted urination. In both of the patients, tumors were resected transurethrally, and histologic examination revealed them to be typical inverted papilloma