OBJECTIVE: The aim of this study was to investigate the relationship between autism spectrum disorder (ASD) and general vaccinations, including measles-mumps-rubella (MMR) vaccine, in Japanese subjects, a population with high genetic homogeneity. PATIENTS AND METHODS: A case-control study was performed. Cases (n=189) were diagnosed with ASD, while controls (n=224) were volunteers from general schools, matched by sex and birth year to cases. Vaccination history and prenatal, perinatal, and neonatal factors from the Maternal and Child Health handbook, which was part of each subject's file, were examined. To determine the relationship between potential risk factors and ASD, crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and the differences in mean values of the quantitative variables between cases and controls were analyzed using an unpaired t-test. Moreover, MMR vaccination and the effect of the number of vaccine injections were investigated using a conditional multiple regression model. RESULTS: For MMR vaccination, the OR was 1.04 (95% CI, 0.65-1.68), and no significant differences were found for the other vaccines. For all of the prenatal, perinatal and neonatal factors, there were no significant differences between cases and controls. Furthermore, regarding the presence of ASD, MMR vaccination and the number of vaccine injections had ORs of 1.10 (95% CI, 0.64-1.90) and 1.10 (95% CI, 0.95-1.26), respectively, in the conditional multiple regression model; no significant differences were found. CONCLUSIONS: In this study, there were not any convincing evidences that MMR vaccination and increasing the number of vaccine injections were associated with an increased risk of ASD in a genetically homogeneous population. Therefore, these findings indicate that there is no basis for avoiding vaccination out of concern for ASD.

A 76-year-old woman presented with vaginal bleeding and discharge in September 2009. She was admitted to our hospital because a tumor of 5 cm in diameter was found in the vagina in a nearby clinic. She was diagnosed with primary vaginal diffuse large B-cell lymphoma (DLBCL) on biopsy of the tumor because CT, MRI and FDG-PET showed no area of lymphomatous involvement other than the vagina and direct involvement into the bladder. She achieved complete response (CR) after chemotherapy followed by localized radiation therapy, but she had a relapse in the central nervous system (CNS) two months after CR. A study of 57 reported cases of primary vaginal lymphoma suggested that the most common histologic type was DLBCL, and most of patients were in a localized stage and responded well to combination of chemotherapy and radiation therapy. To date, two cases of primary vaginal lymphoma with a relapse in the CNS have been reported. We presumed that direct involvement into the bladder of vaginal lymphoma contributed to the relapse in the CNS in this case.

Therapeutic chaperone effect of a valienamine derivative N-octyl 4-epi-β-valienamine (NOEV) was studied in G(M1)-gangliosidosis model mice. Phamacokinetic analysis revealed rapid intestinal absorption and renal excretion after oral administration. Intracellular accumulation was not observed after continuous treatment. NOEV was delivered to the central nervous system through the blood-brain barrier to induce high expression of the apparently deficient β-galactosidase activity. NOEV treatment starting at the early stage of disease resulted in remarkable arrest of neurological progression within a few months. Survival time was significantly prolonged. This result suggests that NOEV chaperone therapy will be clinically effective for prevention of neuronal damage if started early in life hopefully also in human patients with G(M1)-gangliosidosis.

OBJECTIVE: To evaluate the efficacy and safety of intensive post-remission chemotherapy for untreated patients aged 15-69 years with adult acute lymphoblastic leukemia and lymphoblastic lymphoma in a multicenter Phase II study. METHODS: The chemotherapy regimen consisted of induction, post-remission and maintenance for 2 years. The primary endpoint was 5-year progression-free survival, and secondary endpoints included complete remission rate, overall survival and adverse events. Among 115 patients enrolled, 108 eligible patients [median age, 33.5 years (range, 15-69)] including 96 acute lymphoblastic leukemia and 12 lymphoblastic lymphoma were assessed. Other major characteristics were male 50%, T-cell phenotype 21%, Philadelphia chromosome 22%, B-symptom+ 35% and performance status 2/3 22%. RESULTS: Eighty-seven patients achieved complete remission (81%; 95% confidence interval 72-88%), while five (5%) died during the chemotherapy protocol. The median overall survival and progression-free survival were 1.8 years (95% confidence interval, 1.5-2.6) and 1.2 years (95% confidence interval, 0.8-1.6), respectively. Their 5-year overall survival and progression-free survival were 29 and 28%, respectively. The 5-year overall survival of 31 patients who underwent allogeneic (n = 19) or autologous (n = 12) stem cell transplantation during first complete response was 51%. Major non-hematologic toxicities of Grade 3 or greater were infections (21%) and pulmonary complications (6%). When compared with the investigators' previous Phase II trials, JCOG9402 improved progression-free survival and overall survival when compared with JCOG8702; however, it did not show improvement when compared with JCOG9004. CONCLUSIONS: Although the intensified induction and post-remission chemotherapy was feasible and 28% of the patients with adult acute lymphoblastic leukemia or lymphoblastic lymphoma achieved long-term progression-free survival, JCOG9402 did not show improvement.

We investigated the effect of mild (non-noxious) tactile stimulation (stroking) of skin on dopamine (DA) release in the nucleus accumbens (NAc) of rats. A coaxial microdialysis probe was stereotaxically implanted in the NAc and perfused with modified Ringer's solution. Dialysate output from consecutive 5-min periods was injected into a high-performance liquid chromatograph and DA was measured using an electrochemical detector. Bilateral tactile stimulation of the back for 5 min significantly increased DA release in conscious and anesthetized animals. Increased DA release was observed by stimulation of the contralateral, but not ipsilateral, back. DA secretion was also increased with stimulation of the forelimb, hindlimb, and abdomen. These effects were abolished after lesioning the ventral tegmental area (VTA). In contrast, noxious stimulation (pinching) of these areas had no effect on DA secretion. In conclusion, innocuous mechanical stimulation of the skin increases DA release in the contralateral NAc via the VTA.

This paper describes the chemistry of porewater when constructing different soil layers on acidic weathered rock of a closed mine to remediate the surface environment. Three cases were set on a flat surface of the site, all under different layer systems. Case 1 was only composed of weathered rocks. A top neutralization layer was constructed on the weathered rocks in case 2, whereas both an upper low-permeable and middle neutralization layers were constructed on the weathered rocks in case 3. The low-permeable layer of 30 cm thick consists of clay, and the neutralization layer of 30 cm thick consists of the mixture of the weathered rock and calcium carbonate as a neutralizer. Porewater sampling systems and soil sensors to measure temperature, water content, and electrical conductivity were set at different depths. In case 1, steadily high concentrations of heavy metals were observed regardless of the depth, and the pH ranged from 2 to 4. In cases 2 and 3, a dramatic decrease in concentrations of heavy metals was observed, even below the neutralization layer. For both cases, pH values were circumneutral. There were no significant seasonable changes in heavy metals concentrations and pH of porewater by considering the temperature and precipitation. In addition, the water content of the layers in case 3 fluctuated more mildly than that in cases 1 and 2, indicating that the low-permeable layer reduced the rate of infiltration. Therefore, a significant reduction in the load of heavy metals released from the site can be achieved by both implementing neutralization and low-permeable layers.

Flow coefficients v_{n} for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at sqrt[s_{NN}]=200  GeV, are measured relative to event planes Ψ_{n}, determined at large rapidity. We report v_{n} as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The v_{n} are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.

Using 1710 Thoroughbred racehorses in Japan, a cohort study was performed to evaluate the influence of genotypes at four single nucleotide polymorphisms (SNPs) on equine chromosome 18 (ECA18), which were associated in a previous genome-wide association study for racing performance with lifetime earnings and performance rank. In males, both g.65809482T>C and g.65868604G>T were related to performance rank (P = 0.005). In females, g.65809482T>C (P = 1.76E-6), g.65868604G>T (P = 6.81E-6) and g.66493737C>T (P = 4.42E-5) were strongly related to performance rank and also to lifetime earnings (P < 0.05). When win-race distance (WRD) among all winning racehorses and best race distance (BRD) among elite racehorses were considered as the phenotypes, significant associations (P < 0.001) were observed for all four SNPs. The favourable race distance of both elite (BRD) and novice racehorses (WRD) was also associated with genotypes in the ECA18 region, indicating the presence of a gene in this region influencing optimum race distance in Thoroughbred racehorses. Therefore, the association with performance rank is likely due to the bias in the race distances. The location of the SNPs within and proximal to the gene encoding myostatin (MSTN) strongly suggests that regulation of the MSTN gene affects racing performance. In particular, the g.65809482T>C, g.65868604G>T and g.66493737C>T SNPs, or their combinations, may be genetic diagnostic markers for racing performance indicators such as WRD and BRD.

BACKGROUND The role of interleukin (IL) 13 and IL-17A in aspirin-exacerbated respiratory disease (AERD) remains unknown. OBJECTIVE To analyze the IL-13 and IL-17A gene polymorphisms in Japanese patients with AERD. METHODS The single-nucleotide polymorphisms in each gene were examined in patients with AERD, patients with aspirin-tolerant asthma (ATA), and healthy controls. RESULTS Frequencies of the TT/CT genotype of the IL-13 -1111C>T gene were higher than frequencies of the CC genotype in AERD patients compared with ATA patients (P <.001). In female patients with AERD, frequencies of the TT/CT genotype were higher than those of the CC genotype compared with female patients with ATA (P <.001). However, genotype frequencies of IL-13 Arg110Gln did not differ between AERD and ATA patients. Frequencies of the CC genotype of the IL-17A -737C>T gene were higher than those of the TT/CT genotype in AERD patients compared with ATA patients (P =.02). In female patients with AERD, frequencies of the CC genotype were higher than those of the TT/CT genotype compared with female patients with ATA (P =.03). Forced expiratory volume in 1 second (percentage predicted) in AERD patients with the CC genotype of the IL-13 -1111C>T gene was lower than that in the patients with the TT/CT genotype. AERD patients with the TT/CT genotype of the IL-17A -737C>T gene had a higher peripheral total eosinophil count compared with the patients with the CC genotype. The comparison of the clinical characteristics according to the IL-13 Arg110Gln gene polymorphism showed no difference. CONCLUSIONS These findings suggest that the IL-13 -1111C>T and IL-17A -737C>T gene sequence variations might have a role in the development of AERD.

Back-to-back hadron pair yields in d+Au and p+p collisions at √s(NN)=200 GeV were measured with the PHENIX detector at the Relativistic Heavy Ion Collider. Rapidity separated hadron pairs were detected with the trigger hadron at pseudorapidity |η|<0.35 and the associated hadron at forward rapidity (deuteron direction, 3.0<η<3.8). Pairs were also detected with both hadrons measured at forward rapidity; in this case, the yield of back-to-back hadron pairs in d+Au collisions with small impact parameters is observed to be suppressed by a factor of 10 relative to p+p collisions. The kinematics of these pairs is expected to probe partons in the Au nucleus with a low fraction x of the nucleon momenta, where the gluon densities rise sharply. The observed suppression as a function of nuclear thickness, p(T), and η points to cold nuclear matter effects arising at high parton densities.