Genome Wide Association Study of Age at Menarche in the Japanese Population

Age at menarche (AAM) is a complex trait involving both genetic and environmental factors. To identify the genetic factors associated with AAM, we conducted a large-scale meta-analysis of genome-wide association studies using more than 15,000 Japanese female samples. Here, we identified an association between SNP (single nucleotide polymorphism) rs364663 at the LIN28B locus and AAM, with a P-value of 5.49×10−7 and an effect size of 0.089 (year). We also evaluated 33 SNPs that were previously reported to be associated with AAM in women of European ancestry. Among them, two SNPs rs4452860 and rs7028916 in TMEM38B indicated significant association with AAM in the same directions as reported in previous studies (P = 0.0013 with an effect size of 0.051) even after Bonferroni correction for the 33 SNPs. In addition, six loci in or near CCDC85A, LOC100421670, CA10, ZNF483, ARNTL, and RXRG exhibited suggestive association with AAM (P<0.05). Our findings elucidated the impact of genetic variations on AAM in the Japanese population

Genome Wide Association Study of Age at Menarche in the Japanese Population

Age at menarche (AAM) is a complex trait involving both genetic and environmental factors. To identify the genetic factors associated with AAM, we conducted a large-scale meta-analysis of genome-wide association studies using more than 15,000 Japanese female samples. Here, we identified an association between SNP (single nucleotide polymorphism) rs364663 at the LIN28B locus and AAM, with a P-value of 5.49×10−7 and an effect size of 0.089 (year). We also evaluated 33 SNPs that were previously reported to be associated with AAM in women of European ancestry. Among them, two SNPs rs4452860 and rs7028916 in TMEM38B indicated significant association with AAM in the same directions as reported in previous studies (P = 0.0013 with an effect size of 0.051) even after Bonferroni correction for the 33 SNPs. In addition, six loci in or near CCDC85A, LOC100421670, CA10, ZNF483, ARNTL, and RXRG exhibited suggestive association with AAM (P<0.05). Our findings elucidated the impact of genetic variations on AAM in the Japanese population.</p

Effects of Feeding Probiotics on the Localization of Cells Containing Immunoreactive Interleukin-6 in the Intestine of Broiler Chicks

The aim of this study was to examine whether treatments of chicks with probiotics affect the population of cells containing interleukin-6 (IL-6) and IgA in the intestine of broiler chicks. The diets with probiotics, Streptococcus faecalis, Clostridium buthricum, Bacillus mesentericus, were fed from day 0 to 10 of age. The sections of duodenum, pouch and tonsil region of cecum and colon were immunostained for IL-6 and IgA. The IL-6 immunoreaction products were identified in the leukocytes locating in the subepithelial tissues under the mucosal and crypt epithelium and lamina propria, and occationally in the the mucosal and crypt epithelium, in all birds. The density of immunoreactive (ir) IL-6 cell population in the mucosa tended to be lowest in the duodenum and highest in the colon. The density did not differ between control and probiotics groups on day 5; however, that in the cecum pouch and colon was significantly greater in the probiotics group than control on day 10. The IgA immunoreaction products were identified in the mucosal and crypt epithelial cells in all segments of the intestine, and some IgA-positive cells were localized in the lymphoid tissue in the cecum tonsil, whereas differences in their localization were not observed between probiotics and control groups. In conclusion, we suggest that probiotics increases the population of irIL-6 cells in the cecum and colon mucosal tissues of chicks. Because IL-6 is multifunctional cytokine for immune system, the increased IL-6 secretion may affect the immune functions in the intestinal mucosal tissues

Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group

The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m2/day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m2/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70–100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2) plus ACNU (40 mg/m2). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12–35%) and 8% (95% CI, 4–15%). Median PFS was 13 months (95% CI, 9.2–17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67–89%) and 49% (95% CI, 33–57%). Median OS was 11.8 months (95% CI, 8.2–14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS