Search

Progranulin (PGRN) haploinsufficiency resulting from loss-of-function mutations in the PGRN gene causes frontotemporal lobar degeneration accompanied by TDP-43 accumulation, and patients with homozygous mutations in the PGRN gene present with neuronal ceroid lipofuscinosis. Although it remains unknown why PGRN deficiency causes neurodegenerative diseases, there is increasing evidence that PGRN is implicated in lysosomal functions. Here, we show PGRN is a secretory lysosomal protein that regulates lysosomal function and biogenesis by controlling the acidification of lysosomes. PGRN gene expression and protein levels increased concomitantly with the increase of lysosomal biogenesis induced by lysosome alkalizers or serum starvation. Down-regulation or insufficiency of PGRN led to the increased lysosomal gene expression and protein levels, while PGRN overexpression led to the decreased lysosomal gene expression and protein levels. In particular, the level of mature cathepsin D (CTSDmat) dramatically changed depending upon PGRN levels. The acidification of lysosomes was facilitated in cells transfected with PGRN. Then, this caused degradation of CTSDmat by cathepsin B. Secreted PGRN is incorporated into cells via sortilin or cation-independent mannose 6-phosphate receptor, and facilitated the acidification of lysosomes and degradation of CTSDmat. Moreover, the change of PGRN levels led to a cell-type-specific increase of insoluble TDP-43. In the brain tissue of FTLD-TDP patients with PGRN deficiency, CTSD and phosphorylated TDP-43 accumulated in neurons. Our study provides new insights into the physiological function of PGRN and the role of PGRN insufficiency in the pathogenesis of neurodegenerative diseases.

[Background] We previously demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) in the first complete remission (CR1) was recommended for adult patients wih Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) who have a human leukocyte antigen (HLA)-matched related (Leukemia 2011;25:259-265) or unrelated donor (Bone Marrow Transplant 2013;48:1077-1083). However, pediatric-inspired high-intensity chemotherapy dramatically improved the prognosis of adult patients with Ph-negative ALL. Therefore, the optimal treatment strategy for Ph-negative ALL in CR1 has not been established in the era of high-intensity chemotherapy. [Methods] Outcomes of patients with Ph-negative ALL who underwent HSCT from HLA-matched related or unrelated donor in CR1 performed between 2002 and 2011 (HSCT-MRD group and HSCT-MUD group, respectively) were obtained from the Transplant Registry Unified Management Program (TRUMP), which is the registry database of the Japanese Society for Hematopoietic Cell Transplantation (JSHCT). Patients aged between 16 and 24 and between 25 and 65 were analyzed separately, and their outcomes were compared with those of patients who did not receive HSCT in CR1 in clinical studies by Japan Adult Leukemia Study Group (JALSG), ALL-202U study in which patients received chemotherapy designed for pediatric patients (Blood Cancer J 2014;4:e252)(202U group) and ALL-202O study in which patients were randomly assigned to receive adult-type chemotherapy with high-dose or intermediate-dose methotrexate (MTX) therapy (Leukemia 2018;32:626-632)(202O group), respectively. Median durations between diagnosis to HSCT were obtained from the TRUMP data, and only patients who were disease-free more than each median duration were included from the JALSG studies. Risk stratifications were performed based on the white blood cell (WBC) count and cytogenetics. [Results] In patients aged less than 25 who underwent HSCT from related donor, the median duration between diagnosis to HSCT was 188 days. Overall survival (OS) in 202U group (N = 93) was significantly superior compared with OS in HSCT-MRD group (N = 102) (OS at 5 years: 81.8% vs 67.8%, P = 0.016) (Figure 1(A)), and which was attributed to the higher non-relapse mortality in HSCT-MRD group (NRM at 5 years: 1.4% vs 9.5%, P = 0.015). Disease-free survival (DFS) and relapse rate (RR) were similar between two groups (DFS at 5 years: 70.2% vs 62.5%, P = 0.115, and RR at 5 years: 28.4% vs 28.4%, P = 0.689). Higher OS was preserved in younger ( In patients aged more than 24 who underwent HSCT from related donor, the median duration between diagnosis to HSCT was 158 days. OS rate was not different between 202O group (N = 147) and HSCT-MRD group (N = 152) (OS at 5 years: 57.0% vs 60.2%, P = 0.114) (Figure 1(B)). The lower RR was counterbalanced by the higher NRM in HSCT-MRD group (RR at 5 years: 51.6% vs 30.0%, P < 0.001, and NRM at 5 years: 4.1% vs 15.2%, P = 0.015). No difference in OS was demonstrated among any subgroups. Superior DFS in HSCT-MRD group was observed only in high-risk patients (DFS at 5 years: 26.5% vs 57.2%, P = 0.003), but it diminished when only patients who actually received high-dose MTX were included in 202O group (DFS at 5 years: 36.4% vs 57.2%, P = 0.092). In patients aged more than 24 who underwent HSCT from unrelated donor, the median duration between diagnosis to HSCT was 214 days. OS rate was not different between 202O group (N = 138) and HSCT-MUD group (N = 104) (OS at 5 years: 60.0% vs 65.8%, P = 0.563). Superior DFS in HSCT-MUD group was observed even in all patients (DFS at 5 years: 47.2% vs 64.2%, P = 0.029). RR in HSCT-MUD group was lower (RR at 5 years: 14.3%) than that in HSCT-MRD group. [Discussions & Conclusions] High-intensity chemotherapy may change the role of HSCT for Ph-nagative ALL. Improved outcomes in HSCT-MUD group were observed, and it was partially because patients who had long CR before HSCT could underwent HSCT from MUD in CR1. Disclosures Kako: Bristol-Myers Squibb: Honoraria; Pfizer Japan Inc.: Honoraria. Tanaka:Bristol-Myers Squibb: Research Funding. Ichinohe:JCR Pharmaceuticals: Honoraria; Celgene: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Astellas Pharma: Research Funding; Chugai Pharmaceutical Co.: Research Funding; CSL Behring: Research Funding; Eisai Co.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; Ono Pharmaceutical Co.: Research Funding; Pfizer: Research Funding; Nippon Shinyaku Co.: Research Funding; MSD: Research Funding; Otsuka Pharmaceutical Co.: Research Funding; Repertoire Genesis Inc.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; Taiho Pharmaceutical Co.: Research Funding; Takeda Pharmaceutical Co.: Research Funding; Zenyaku Kogyo Co.: Research Funding; Alexion Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria. Kurahashi:Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Novartis Pharma Co., Ltd.: Honoraria; Takeda Pharmaceutical Co., Ltd: Honoraria; Bristol-Myers Squibb, Ltd.: Honoraria. Usui:Alexion Pharmaceuticals: Other: Personal Fees; Bristol-Myers Squibb: Other: Personal Fees, Research Funding; Kyowa-Hakko-Kirin Co.Ltd.: Other: Personal Fees; Astellas Pharma Inc.: Other: Personal Fees; Huya Bioscience International: Other: Personal Fees; Nippon Shinyaku Co.: Other: Personal Fees; SymBio Pharmaceuticals: Other: Personal Fees; Celgene Corporation: Other: Personal Fees; Pfizer: Other: Personal Fees, Research Funding; Takeda Pharmaceutical Co. Ltd: Other: Personal Fees; Cmic Co: Other: Personal Fees; Otsuka Pharmaceutical Co.Ltd.: Other: Personal Fees; AbbVie Inc: Other: Personal Fees. Kiyoi:Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Astellas Pharma Inc.: Honoraria, Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Pfizer Japan Inc.: Honoraria; Perseus Proteomics Inc.: Research Funding; Otsuka Pharmaceutical Co.,Ltd.: Research Funding; Bristol-Myers Squibb: Research Funding; Daiichi Sankyo Co., Ltd: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; FUJIFILM Corporation: Research Funding; Takeda Pharmaceutical Co., Ltd.: Research Funding. Matsumura:Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; Otsuka Pharmaceutical: Consultancy, Research Funding; Pfizer: Research Funding, Speakers Bureau. Miyazaki:Chugai: Research Funding; Otsuka: Honoraria; Novartis: Honoraria; Nippon-Shinyaku: Honoraria; Dainippon-Sumitomo: Honoraria; Kyowa-Kirin: Honoraria. Atsuta:CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria; Kyowa Kirin Co., Ltd: Honoraria.

In soybean, the I gene inhibits pigmentation over the entire seed coat, resulting in yellow seeds. It is thought that this suppression of seed coat pigmentation is due to naturally occurring RNA silencing of chalcone synthase genes (CHS silencing). Fully pigmented seeds can be found among harvested yellow seeds at a very low percentage. These seed coat pigmented (scp) mutants are generated from yellow soybeans by spontaneous recessive mutation of the I gene. A candidate for the I gene, GmIRCHS, contains a perfect inverted repeat (IR) of a CHS pseudogene (pseudoCHS3) and transcripts of GmIRCHS form a double-stranded CHS RNA that potentially triggers CHS silencing. One CHS gene, ICHS1, is located 680 bp downstream of GmIRCHS. Here, the GmIRCHS-ICHS1 cluster was compared in scp mutants of various origins. In these mutants, sequence divergence in the cluster resulted in complete or partial loss of GmIRCHS in at least the pseudoCHS3 region. This result is consistent with the notion that the IR of pseudoCHS3 is sufficient to induce CHS silencing, and further supports that GmIRCHS is the I gene.

Ce 3+ -doped and Ce 3+ /Li + -codoped SrAlSi 4 N 7 phosphors were synthesized by gas pressure sintering of powder mixtures of Sr 3 N 2 , AlN, α-Si 3 N 4 , CeN and Li 3 N. The phase purity, electronic crystal structure, photoluminescence properties of SrAlSi 4 N 7 :Ce 3+ (Ce 3+ /Li + ) were investigated in this work. The band structure calculated by the DMol 3 code shows that SrAlSi 4 N 7 has a direct band gap of 3.87 eV. The single crystal analysis of Ce 3+ -doped SrAlSi 4 N 7 indicates a disordered Si/Al distribution and nitrogen vacnacy defects. SrAlSi 4 N 7 was identified as a major phase of the fired powders, and Sr 5 Al 5 Si 21 N 35 O 2 and AlN as minor phases. Both Ce 3+ and Ce 3+ /Li + doped SrAlSi 4 N 7 phosphors can be efficiently excited by near-UV or blue light and show a broadband yellow emission peaking around 565 nm. A highest external quantum efficiency of 38.3% under the 450 nm excitation was observed for the Ce 3+ /Li + -doped SrAlSi 4 N 7 (5 mol%). A white light LED lamp with color temperature of 6300 K and color rendering index of Ra =78 was achieved by combining Sr 0.97 Al 1.03 Si 3.997 N\94\maccounttest14=t0005_18193 7 :Ce 3+ 0.03 with a commercial blue InGaN chip. It indicates that SrAlSi 4 N 7 :Ce 3+ is a promising yellow emitting down-conversion phosphor for white LEDs.

The effects of muscle contractions on the profile of postcontraction resting intracellular Ca2+ ([Ca2+]i) accumulation in Type 1 diabetes are unclear. We tested the hypothesis that, following repeated bouts of muscle contractions, the rise in resting [Ca2+]i evident in healthy rats would be increased in diabetic rats and that these changes would be associated with a decreased cytoplasmic Ca2+-buffering capacity. Adult male Wistar rats were divided randomly into diabetic (DIA; streptozotocin, ip) and healthy control (CONT) groups. Four weeks later, animals were anesthetized and spinotrapezius muscle contractions (10 sets of 50 contractions) were elicited by electrical stimulation (100 Hz). Ca2+ imaging was achieved using Fura-2 AM in the spinotrapezius muscle in vivo (i.e., circulation intact). The ratio (340/380 nm) was determined from fluorescence images following each set of contractions for estimation of [Ca2+]i. Also, muscle Ca2+ buffering was studied in individual myocytes microinjected with 2 mM Ca2+ solution. After muscle contractions, resting [Ca2+]i in DIA increased earlier and more rapidly than in CONT ( P < 0.05 vs. precontraction). Peak [Ca2+]i in response to the Ca2+ injection was significantly higher in CONT (25.8 ± 6.0% above baseline) than DIA (10.2 ± 1.1% above baseline). Subsequently, CONT [Ca2+]i decreased rapidly (2+ uptake) protein levels were evident between CONT and DIA, whereas ryanodine receptor (Ca2+ release) protein level and mitochondrial oxidative enzyme activity (succinate dehydrogenase) were decreased in DIA ( P < 0.05). In conclusion, diabetes impairs resting [Ca2+]i homeostasis following muscle contractions. Markedly different responses to Ca2+ injection in DIA vs. CONT suggest fundamentally deranged Ca2+ handling.

Objective To investigate the short-term efficacy of tamsulosin treatment for patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) according to baseline prostate volume (PV). Methods Tamsulosin, 0.2 mg/day, was prospectively given to 112 patients aged 50 years or older who had International Prostate Symptom Scores (IPSS) ≥ 8. The short-term efficacy was analyzed using the IPSS, quality of life (QOL) index, BPH problem index (BPI), maximum flow rate (Qmax) and postvoid residual urine volume (PVR) at 4 weeks and 3 months after treatment considering the estimated PV at baseline. Results Of the 112 patients, 81 and 31 had PV of

The tolerability and efficacy of sofosbuvir and ribavirin in patients infected with hepatitis C virus (HCV) genotype 2 were investigated under actual clinical conditions. A total of 208 patients with chronic HCV genotype 2 infection were treated with sofosbuvir 400 mg and ribavirin (weight-based dosing) for 12 weeks. Treatment discontinuation and sustained virological response 12 (SVR12) were evaluated. Moreover, factors associated with SVR12, hemoglobin decreasing to less than 10 g/dL during treatment, and alanine aminotransferase (ALT) non-normalization after treatment were evaluated. In all patients, SVR12 responses were 96.1% (200/208). About 6 of 8 patients (3.8%) who did not achieve SVR12 were re-treatment patients, and eight patients who did not achieve SVR all had liver cirrhosis. Multivariate analysis also identified body mass index (OR = 0.79; P < 0.001), platelet count (OR = 0.88; P = 0.003), and estimated glomerular filtration rate (eGFR) (OR = 0.96; P = 0.007) as independent contributing factors associated with hemoglobin decreasing to less than 10 g/dL during treatment, and only Mac-2 Binding Protein Glycosylation isomer (M2BpGi) (OR = 2.46; P = 0.017) as an independent contributing factor associated with ALT non-normalization after treatment. Cirrhotic patients may have a relatively high rate of treatment failure. In patients whose M2BpGi levels are elevated, their ALT tended to not normalize after treatment completion. These patients who did not achieve normalization of ALT after sofosbuvir plus RBV treatment need more careful observation for emergence of hepatocellular carcinoma even after achievement of SVR.

Purpose We aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). Materials and methods Among 1,087 patients with UCB who had undergone RC at our 11 institutions between 1990 and 2010, 306 patients who subsequently developed distant metastasis or local recurrence or both were identified. Clinical data were collected with medical record review. Univariate and multivariate Cox regression models addressed OS after recurrence. A nomogram predicting postrecurrence OS was constructed based on Cox proportional hazards model, without using postrecurrence factors (systemic chemotherapy and resection of metastasis). The performance of the nomogram was internally validated by assessing concordance index and calibration plots. Results Of the 306 patients, 268 died during follow-up with a median survival of 7 months (95% CI: 5.8–8.5). Postrecurrence chemotherapy was administered in 119 patients (38.9%). Multivariable analysis identified 9 independent predictors for OS; period of time from RC to recurrence (time-to-recurrence), symptomatic recurrence, liver metastasis, hemoglobin level, serum alkaline phosphatase level, serum lactate dehydrogenase level, serum C-reactive protein level, postrecurrence chemotherapy, and resection of metastasis. A nomogram was formed with the following 5 variables to predict OS: time-to-recurrence, symptomatic recurrence, liver metastasis, albumin level, and alkaline phosphatase level. Concordance index rate was 0.75 (95% CI: 0.72–0.78) by internal validation using Bootstraps with 1,000 resamples. Calibration plots showed that the nomogram fitted well. Conclusions We identified 9 clinicopathological factors as independent OS predictors in postcystectomy recurrence of UCB. We also created a validated nomogram with 5 variables that efficiently stratified those patients regardless of eligibility for chemotherapy. The nomogram would be useful for acquiring relevant prognostic information and for stratifying patients for clinical trials.

Objectives To determine the characteristics of testicular germ cell tumors in older patients. Methods A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register the testicular cancers diagnosed in 2005 and 2008. The survey included age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, treatment and clinical outcomes. These factors were compared between patients aged ≥50 years and those aged

We investigate fabrication of a photonic-crystal structure by air-hole retained crystal regrowth using TBAs-based MOVPE for GaAs based photonic-crystal lasers. Air holes having a filling factor of 10 % (the depth was 250 nm and the width was 110 nm) are successfully embedded. The embedded air holes show characteristic shapes due to anisotropy of growth rate along different crystal planes, such as gallium face and arsenic face. Furthermore, a low threshold of 0.5 kAcm−2 lasing is achieved with the fabricated structure.

Researchers experimentally demonstrate on-demand transfer of trapped photons on a photonic crystal chip for the first time., Photonic crystal nanocavities, which have modal volumes of the order of a cubic wavelength in the material, are of great interest as flexible platforms for manipulating photons. Recent developments in ultra-high quality factor nanocavities with long photon lifetimes have encouraged us to develop an ultra-compact and flexible photon manipulation technology where photons are trapped in networks of such nanocavities. The most fundamental requirement is the on-demand transfer of photons to and from the trapped states of arbitrary nanocavities. We experimentally demonstrate photon transfer between two nearly resonant nanocavities at arbitrary positions on a chip, triggered by the irradiation of a third nonresonant nanocavity using an optical control pulse. We obtain a high transfer efficiency of ~90% with a photon lifetime of ~200 ps.

In-band full-duplex, allowing simultaneous transmission and reception on the same device over the same frequency, can double the spectral efficiency theoretically. However, the severe self-interference challenges the physical layer design. Thus, to simplify the interference cancellation (IC), the space division full-duplex (SDFD) is considered, where two spatial-separated transmission points (TPs), e.g., base stations, simultaneously serve the same cell in downlink (DL) and uplink (UL), respectively. In this paper, assuming the TP has digital-domain IC capability only, we study the SDFD scheme in heterogeneous network, i.e., a small cell (named SDFD-cell) is served as SDFD via macro TP (MTP) in DL and small TP (STP) in UL. Due to the inter-TP interference, the capacity of SDFD-cell is restricted by the digital-domain IC. Moreover, SDFD degrades the performance of other non-SDFD-cells. Therefore, we propose a joint scheduling and precoding design algorithm. The scheduling scheme selects a user equipment (UE) pair in the SDFD-cell for DL and UL transmissions as proportional fairness metric. Then, an optimal precoder is designed for MTP to reduce the interference in both SDFD-cell and non-SDFD-cells. The simulation results verify that the proposed algorithm can significantly improve the capacity of the SDFD-cell with limited capacity degradation in non-SDFD-cells.

Background Type 1 autoimmune pancreatitis (AIP) is clinically characterized by a response to steroid therapy. Despite having a favorable prognosis, AIP has a high relapse rate and factors predicting relapse in AIP patients treated with steroids have not yet been established. Methods A retrospective chart review was conducted of 32 newly diagnosed type 1 AIP patients who had undergone enhanced computed tomography (CT) pre- and post-steroid therapy. Results Ten patients experienced relapse. Pancreatic volume was reduced significantly in all patients (pre-treatment volume, 88.5 ± 32.9 cm3 vs. post-treatment volume, 45.4 ± 21.1 cm3; P

Objectives To improve the perioperative care for radical prostatectomy patients at a multi-institutional level and practice. Methods A prospective multi-institutional study involving 50 hospitals was carried out in cooperation with the Japanese Society of Endourology. As the first step, a consensus meeting was held to establish a standardized perioperative care plan. Second, the clinical pathways were individually developed and revised according to the standardized care plan in each of the participating hospitals. Patterns of perioperative care, including preoperative hospital stay, resuming meals and ambulation, removal of pelvic drain and urethral catheter, antimicrobial administration, and postoperative hospital stay, were compared before (2007) and after developing/revising pathways (2009). Furthermore, actual practice and complications before and after implementing the pathways were investigated. Results Except for resuming ambulation, all perioperative pathways were significantly shortened with the adoption of the newly defined clinical pathway (P

Objective To comprehensively analyze the 5-year outcomes of tamsulosin treatment for patients with benign prostatic hyperplasia. Methods Tamsulosin (0.2 mg/day) was given to 112 patients who had International Prostate Symptom Scores ≥8. They were prospectively followed for 5 years with periodic evaluation. If tamsulosin had to be discontinued, the reason was determined. Treatment failure was considered in the case of disease progression (postvoid residual urine volume ≥200 mL, acute urinary retention, febrile urinary tract infection or hydronephrosis as a result of bladder outlet obstruction), conversion to other α1-blockers or need for surgery. An intention-to-treat analysis was carried out. Results A total of 34 patients (30.4%) continued the same medication for the overall study period, whereas 78 patients (69.6%) discontinued the medication. International Prostate Symptom Scores, Benign Prostatic Hyperplasia Problem Index and Quality of Life Index were significantly improved over the 5-year period. Treatment failure was observed in 21 patients (18.8%). Baseline prostate volume and postvoid residual urine volume were independent factors to predicting treatment failure. A total of 21 patients (18.8%) discontinued tamsulosin because of an improvement of symptoms. They were younger and had lower prostate-specific antigen levels than the remaining 91 patients. Their symptoms were stable even 1 year after termination of therapy. Conclusions Long-term efficacy of tamsulosin was observed, although only a small portion of patients continued the treatment. α1-blocker monotherapy might be not appropriate for achieving a good long-term outcome in patients with a large prostate volume and a large amount of postvoid residual urine volume. Persistent improvement of symptoms, even after termination of tamsulosin, was observed in young patients with low prostate-specific antigen levels.

Finite element (FE) simulations were conducted of full-car oblique side collision with a Hybrid III 3-year-old dummy and a child FE model seated in a child restraint system (CRS). Although the head of the Hybrid III 3-year-old did not have contact with the door, the head of the child FE model impacted the side of the door window sill. In the real world, the misuse of the CRS is observed frequently. A prescribed structural motion method was used to evaluate efficiently the influence of slack of the CRS harness and car seat belt. The CRS harness slack made the head of the child FE model impact on the top of the door window sill at a high velocity, and the head injury criterion (HIC) was comparable with the injury assessment reference value (IARV). It was found that the CRS harness slack can be one of the important factors of severe head injuries due to contact with the car interior, which is observed frequently in accidents.

While the cultivated soybean, Glycine max (L.) Merr., is more recalcitrant to pod dehiscence (shattering-resistant) than wild soybean, Glycine soja Sieb. & Zucc., there is also significant genetic variation in shattering resistance among cultivated soybean cultivars. To reveal the genetic basis and develop DNA markers for pod dehiscence, several research groups have conducted quantitative trait locus (QTL) analysis using segregated populations derived from crosses between G. max accessions or between a G. max and G. soja accession. In the populations of G. max, a major QTL was repeatedly identified near SSR marker Sat_366 on linkage group J (chromosome 16). Minor QTLs were also detected in several studies, although less commonality was found for the magnitudes of effect and location. In G. max × G. soja populations, only QTLs with a relatively small effect were detected. The major QTL found in G. max was further fine-mapped, leading to the development of specific markers for the shattering resistance allele at this locus. The markers were used in a breeding program, resulting in the production of near-isogenic lines with shattering resistance and genetic backgrounds of Japanese elite cultivars. The markers and lines developed will hopefully contribute to the rapid production of a variety of shattering-resistant soybean cultivars.

Soybean dwarf virus (SbDV) causes serious dwarfing, yellowing and sterility in soybean (Glycine max). The soybean cv. Adams is tolerant to SbDV infection in the field and exhibits antibiosis to foxglove aphid (Aulacorthum solani), which transmits SbDV. This antibiosis (termed “aphid resistance”) is required for tolerance to SbDV in the field in segregated progenies of Adams. A major quantitative trait locus, Raso1, is reported for foxglove aphid resistance. Our objectives were to fine map Raso1 and to reveal whether Raso1 alone is sufficient to confer both aphid resistance and SbDV tolerance. We introduced Raso1 into cv. Toyomusume by backcrossing and investigated the degree of aphid antibiosis to foxglove aphid and the degree of tolerance to SbDV in the field. All Raso1-introduced backcross lines showed aphid resistance. Interestingly, only one Raso1-introduced backcross line (TM-1386) showed tolerance to SbDV in the field. The results demonstrated Raso1 alone is sufficient to confer aphid resistance but insufficient for SbDV tolerance. Tolerance to SbDV was indicated to require additional gene(s) to Raso1. Additionally, Raso1 was mapped to a 63-kb interval on chromosome 3 of the Williams 82 sequence assembly (Glyma1). This interval includes a nucleotide-binding site–leucine-rich repeat encoding gene and two other genes in the Williams 82 soybean genome sequence.

Mucoepidermoid carcinoma of the intrahepatic bile duct is a rare variant of cholangiocarcinoma: it is composed of mucus-secreting squamous cells and glandular cells within the same nests. This tumor is very aggressive, with high-grade malignancy, and has a poor prognosis. In the international literature, only 17 cases of mucoepidermoid carcinoma originating in the hepatic bile duct system have been reported until now. We report an autopsy case of mucoepidermoid carcinoma of the intrahepatic bile duct with metastasis to the cranial skin in a Japanese man who was more than 70 years old. This cancer metastasizes to many organs, but skin metastasis is extremely rare.

Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) is one of the most damaging pests of soybean (Glycine max (L.) Merr.). Host plant resistance has been the most effective control method. Because of the spread of multiple SCN races in Hokkaido, the Tokachi Agricultural Experiment Station has bred soybeans for SCN resistance since 1953 by using 2 main resistance resources PI84751 (resistant to races 1 and 3) and Gedenshirazu (resistant to race 3). In this study, we investigated the genetic relationships of SCN resistance originating from major SCN resistance genes in Gedenshirazu and PI84751 by using SSR markers. We confirmed that race 1 resistance in PI84751 was independently controlled by 4 genes, 2 of which were rhg1 and Rhg4. We classified the PI84751- type allele of Rhg1 as rhg1-s and the Gedenshirazu-type allele of Rhg1 as rhg1-g. In the cross of the Gedenshirazu-derived race 3-resistant lines and the PI84751-derived races 1- and 3-resistant lines, the presence of rhg1-s and Rhg4 was responsible for race 1-resistance. These results indicated that it was possible to select race 1 resistant plants by using marker-assisted selection for the rhg1-s and Rhg4 alleles through a PI84751 origin × Gedenshirazu origin cross.

Scientists demonstrate strong coupling between distant nanocavities separated by more than 100 wavelengths as well as dynamic control over the coupling state. The strong coupling state can be stopped on demand by irradiating one of the nanocavities with a control pulse, thus freezing the photon state.

Background: The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer. Methods: Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray. Results: From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann–Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae. Conclusions: Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer. Impact: The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies. Cancer Epidemiol Biomarkers Prev; 20(10); 2195–203. ©2011 AACR.

The objectives of this paper were to determine the level of oxidative stress in atrophied gastrocnemius, and to verify the effect of molecular hydrogen (H2) saturated alkaline electrolyzed water (HSW) on gastrocnemius atrophy by modifying the redox status, indicated by 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and superoxide dismutase (SOD)-like activity. Female Wistar rats were divided into four groups: (1) the control (CONT); (2) the Hindlimb unloading (HU, for 3 weeks) given purified normal water (HU-NW); (3) the HU given alkaline electrolyzed reduced water (HU-AEW); and (4) the HU given HSW (HU-HSW). We showed that 8-OHdG, but not MDA, significantly increased by 149% and 145% in HU-NW and HU-AEW, respectively, when compared with CONT. In contrast, there was a trend toward suppression in 8-OHdG levels (increased by 95% compared with CONT) by treatment of HSW, though this effect was not prominent. Additionally, SOD-like activity significantly increased in both HU-NW (184%) and HU-AEW (199%) when compared with CONT. This result suggests the elevation of O2-· in the atrophied gastrocnemius. However, upregulation of SOD-like activity in the HU-HSW was increased by only 169% compared with CONT, though this difference is too small to detect statistical significance. HU led to 13% and 15% reduction of gastrocnemius wet weights in HU-NW and HU-AEW, respectively, compared with CONT. And the reduction of gastrocnemius wet weights in HU-HSW was attenuated by 7% compared with CONT. The gastrocnemius wet weights in the HU-HSW group were significantly greater than those in the HU-AEW, but not statistically significant with HU-NW. These results indicate that HU causes an increase in oxidative stress, but, in this experimental protocol, continuous consumption of HSW during HU does not demonstrate successful attenuation of oxidative stress and HU-mediated gastrocnemius atrophy.

Background: Early detection is essential to improve the outcome of patients with pancreatic cancer. A noninvasive and cost-effective diagnostic test using plasma/serum biomarkers would facilitate the detection of pancreatic cancer at the early stage. Methods: Using a novel combination of hollow fiber membrane–based low-molecular-weight protein enrichment and LC-MS-based quantitative shotgun proteomics, we compared the plasma proteome between 24 patients with pancreatic cancer and 21 healthy controls (training cohort). An identified biomarker candidate was then subjected to a large blinded independent validation (n = 237, validation cohort) using a high-density reverse-phase protein microarray. Results: Among a total of 53,009 MS peaks, we identified a peptide derived from CXC chemokine ligand 7 (CXCL7) that was significantly reduced in pancreatic cancer patients, showing an area under curve (AUC) value of 0.84 and a P value of 0.00005 (Mann–Whitney U test). Reduction of the CXCL7 protein was consistently observed in pancreatic cancer patients including those with stage I and II disease in the validation cohort (P < 0.0001). The plasma level of CXCL7 was independent from that of CA19-9 (Pearson's r = 0.289), and combination with CXCL7 significantly improved the AUC value of CA19-9 to 0.961 (P = 0.002). Conclusions: We identified a significant decrease of the plasma CXCL7 level in patients with pancreatic cancer, and combination of CA19-9 with CXCL7 improved the discriminatory power of the former for pancreatic cancer. Impact: The present findings may provide a new diagnostic option for pancreatic cancer and facilitate early detection of the disease. Cancer Epidemiol Biomarkers Prev; 20(1); 160–71. ©2011 AACR.

Study Type – Therapy (RCT) Level of Evidence 1b OBJECTIVE • To confirm the recurrence-preventing efficacy and safety of 18-month bacillus Calmette-Guerin (BCG) maintenance therapy for non-muscle-invasive bladder cancer. PATIENTS AND METHODS • The enrolled patients had been diagnosed with recurrent or multiple non-muscle-invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT). • The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non-maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence-free survival (RFS). RESULTS • Efficacy analysis was performed for 115 of the full-analysis-set population of 116 eligible patients, including 41 maintenance group patients, 42 non-maintenance group patients and 32 epirubicin group patients. • At the 2-year median point of the overall actual follow-up period, the final cumulative RFS rates in the maintenance, non-maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively. • The RFS following TURBT was significantly prolonged in the maintenance group compared with the non-maintenance group (generalized Wilcoxon test, P= 0.0190). CONCLUSION • BCG maintenance therapy significantly prolonged the post-TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.

Mobilized stem cells in the peripheral blood (PB) must be efficiently harvested at the appropriate time before autologous PB stem cell (PBSC) transplantation. Enumeration of CD34+ cells in the PB before apheresis predicts the number of PBSCs that can be collected, but the cytometric techniques used are complex and expensive. Therefore, it is necessary to identify an alternative to the CD34+ cell count in PBSC harvest-time monitoring. Fully automated flow cytometry using blood cell counters now allows reliable quantification of immature myeloid cells in the PB, referred to as hematopoietic progenitor cells (HPC), and reticulated platelets, expressed as the immature platelet fraction (IPF). Immature or reticulated platelets are thought to correlate with thrombopoietic activity of the marrow. Following a chemotherapy nadir, the recovery of white blood cell and platelet counts has been used to determine the right time for apheresis. Therefore, we examined whether the HPC count and IPF value could be used to predict PBSC mobilization in 20 patients with hematological malignancies. The HPC count was found to be correlated with the CD34+ cell count (r = 0.84, P < 0.01), whereas the IPF value was not (r = 0.37, P = 0.44). Therefore, the HPC count, but not the IPF value, is a possible predictor of the timing of autologous stem cell transplantation.

Objectives: To investigate the urodynamic effects of solifenacin in untreated female patients with symptomatic overactive bladder (OAB). Methods: A total of 52 untreated female patients with OAB symptoms were given 5 mg solifenacin once daily for 12 weeks. Before and after treatment, the frequency volume chart, overactive bladder symptom score (OABSS), postvoid residual volume, filling cystometry and adverse events were evaluated. Results: After solifenacin treatment, OAB symptoms were improved, voided volume was increased and voiding number was decreased. Bladder capacities at the first sensation of bladder filling, first desire to void and strong desire to void were significantly increased. Intravesical pressure at the first sensation of bladder filling was significantly decreased. Detrusor overactivity (DO) disappeared in five patients. For 28 patients with persisting DO after treatment, bladder capacity at DO was significantly increased. Both groups with and without DO at baseline had significant improvements of OAB symptoms. Conclusions: Solifenacin urodynamically increases bladder capacity in female patients with symptomatic OAB.

We review the recent progress in thin-film silicon solar cells with photonic crystals, where absorption enhancement is achieved by using large-area resonant effects in photonic crystals. First, a definitive guideline for enhancing light absorption in a wide wavelength range (600–1100 nm) is introduced, showing that the formation of multiple band edges utilizing higher-order modes confined in the thickness direction and the introduction of photonic superlattice structures enable significant absorption enhancement, exceeding that observed for conventional random scatterers. Subsequently, experimental evidence of this enhancement is demonstrated for a variety of thin-film Si solar cells: ~500-nm-thick ultrathin microcrystalline silicon cells, few-µm-thick microcrystalline silicon cells, and ~20-µm-thick thin single-crystalline silicon cells. The high short-circuit current densities and/or efficiencies observed for each cell structure confirm the effectiveness of using multiple band-edge resonant modes of photonic crystals for enhancing broadband absorption in actual solar cells.

Although a cell culture system for HCV JFH-1 strain has been developed, no robust cell culture system for serum-derived HCV is available. In this study, we have established systems capable of monitoring infection with JFH-1 virus based on specific reporter gene expression through proteolysis of chimeric transcription factors by HCV NS3/4A protease. We utilized a transcriptional factor Gal4-TBP that synergistically enhances transcription of the GAL4UAS and HIV-1 LTR tandem promoter with the Tat protein. We constructed chimeric Tat and Gal4-TBP transcription factors containing the HCV NS3/4A cleavage sequence of a mitochondria-resident IPS-1, but not those of the HCV polyprotein, and manipulated them to localize in the ER. Upon infection with JFH-1 virus, the transcription factors were efficiently cleaved by HCV protease, migrated into the nucleus and activated the reporter gene under the tandem promoter. Upon infection with JFH-1 virus, the Huh7OK1/TG-Luc cell line carrying the transcription factors and a luciferase gene under the promoter expressed luciferase in a dose-dependent manner in close correlation with HCV RNA replication. Huh7OK1/TG-LNGFR cells carrying the transcription factors and a cDNA of human low affinity nerve growth factor receptor under the promoter were selectively concentrated by immunomagnetic cell sorting upon infection with JFH-1 virus. These results indicate that the chimeric constructs bearing the ER-resident IPS-1 sequence are specifically recognized and efficiently cleaved by HCV protease and are harnessed for detection of HCV replication and for recovery of HCV-infected cells. This strategy may be applicable for the establishment of cell culture systems for the isolation of serum-derived HCV.

Helical poly(L-glutamate) with carbazole (Cz) side chains (PCELG) was synthesized as a hole-transport host material for a dye-doped polymer electroluminescence (EL) device. The main- and side-chain conformations were investigated by a combination of polarized infrared spectroscopy and semiempirical quantum chemical calculation. In an electrically poled PCELG crystalline film, the main chain was found to assume a right-handed α-helical conformation with an order parameter of ∼0.8. The Cz plane at the terminal side chain is inclined by about 44° toward the helical axis, creating a regular stacked structure conforming to the rigid α-helical backbone. The principal EL characteristics of these devices were determined and compared with those of devices made with poly(N-vinyl carbazole) (PVCz). For green and blue light, EL devices using PCELG exhibited luminance efficiencies comparable to those using PVCz. To the best of our knowledge, this was the first demonstration of primary colors emitted by an organic EL device with a polypeptide hole-transport host material. The experimental results suggested that the total concentration and spatial arrangement of the Cz groups play an important role in determining the EL characteristics of dye-doped polymer EL devices. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 496–502, 2010

症例は86歳，男性．2009年1月23日右鼠径部腫瘤の主訴で当院受診．当初は嵌頓，腸閉塞症状等認めず，待機的手術予定であったが，2009年1月27日，上腹部痛の主訴のもと当科再診，腹部単純X線でNiveauを認め，腹部骨盤CT検査で右鼠径部に腸管の嵌頓，上腹部にWhirl signを認めた．右嵌頓鼠径ヘルニアによる続発性小腸軸捻転症を疑い，同日腹腔鏡補助下に緊急手術を施行した．腹腔内は全体に拡張した小腸を認め，回腸末端のRichter型右嵌頓鼠径ヘルニアを認めた．嵌頓した腸管を鉗子で腹腔内に整復，嵌頓部腸管の血流障害は認めなかった．さらに検索したところ，上腸間膜動静脈を軸とし，反時計方向に約720度の軸捻転を認めたため，腸管整復術を施行した．捻転部小腸の血流障害は認めず，腸管切除は不要であった．Mesh Plug法による右鼠径ヘルニア根治術を施行し，手術を終了した．術後経過は良好で，術後17日目に軽快退院した．

The number and distribution of branches in soybean plants influence seed yield through effects on the efficiency of light utilization as well as on tolerance to lodging. We have developed recombinant inbred lines (RILs) from a cross between two experimental determinant lines, which differ in branching number. The 172 RILs were divided into four maturity groups according to their alleles for two maturity loci, E1 and E3, and were planted separately to avoid confounding effects of competition. The late-maturity RIL groups with the E1 genotype were grown in two different locations, whereas the early-maturity RIL groups with the e1 genotype were planted at one location. Analysis of all lines resulted in the identification of five quantitative trait loci (QTLs) for branching number, designated qBr1 to qBr5. Among these QTLs, qBr1 and qBr2 were mapped to the proximal regions of the E1 and E3 loci, respectively. The other three QTLs were mapped to regions distant from any known maturity loci and were detected only in the presence of the E1 genotype, indicating that they interact with qBr1. Our results suggest that branching number might be controlled genetically by the identified QTLs, even though the maturity loci substantially affect branching phenotype.

我々は2002年４月から2009年１月までに初回同種移植を施行した，急性骨髄性白血病（40症例），ハイリスク骨髄異形成症候群（10症例）計50症例について，移植前・移植時予後因子を検討するために後方視的解析を行った．平均年齢は41.4歳．32%が移植時非寛解期であり，また44%が染色体リスク分類において予後不良群であった．３年の全生存率，無進行生存率，再発率，移植関連死亡率はそれぞれ48.8%，41.3%，38.9%，27.8%であった．移植前・移植時因子の予後に与える影響を単変量・多変量解析で検討し，染色体リスクが最も重要な因子として同定された．さらに，染色体リスクで層別化し解析を加えたところ，染色体リスクによって，移植前処置の強度および移植片対宿主病の対応を変更する，層別化治療の検討が必要と考えられる結果を得たので報告する．

Days from full maturity to combine harvest maturity (DFC) is a major concern in combine harvesting of soybeans (Glycine max (L.)), especially in northern Japan, which has a short harvesting period. The combine harvest maturity, which was defined as the day at which the moisture content of the stem reached 30%, was analyzed using 7 soybean varieties for 3 yr in Hokkaido. There were significant differences in DFC among varieties (12 to 31 d) and among the 3 yr (16 to 25 d). DFC was closely associated with dry matter partitioning to stem (DMPS) at full maturity, that is, high DMPS increased DFC. The relationship between DMPS and DFC was examined by pod removal experiments conducted for 2 yr. In the soybean plants with high DMPS pod removal increased the stem desiccation period and DFC. These results indicated that DMPS at full maturity is an informative indicator for predicting the harvest maturity in the combine harvesting system.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To investigate whether bladder outlet obstruction (BOO), detrusor underactivity (DUA) and detrusor overactivity (DO) affect the long-term outcome of transurethral resection of the prostate (TURP) for patients having lower urinary tract symptoms suggestive of benign prostatic obstruction. PATIENTS AND METHODS Of 92 patients who had TURP after a urodynamic study between 1995 and 1997, 43 (47%) were alive at the time of the survey in February 2008. Nine patients were excluded because of prostate cancer, neurological diseases and the impossibility of symptomatic examination. The International Prostate Symptom Score (IPSS) and quality-of-life (QoL) index were determined at baseline, 3 months, 3, 7 and 12 years after surgery for 34 patients. RESULTS Although the improved IPSS and QoL index at 3 months gradually deteriorated with time, patients at 12 years were still significantly better than those at baseline. The IPSS in patients without BOO deteriorated faster than in those with it, whereas neither DUA nor DO influenced the slope of change in IPSS. Regardless of the preoperative urodynamic findings, the QoL index remained improved for 12 years. Two-thirds of patients with DUA but not BOO were satisfied with their urinary condition at 12 years. CONCLUSION The symptomatic improvement provided by TURP lasts for >10 years, although there is a gradual deterioration with time. The QoL index remained improved for 12 years regardless of the preoperative urodynamic findings.

In order to facilitate the discovery and investigation of anti-cancer therapeutics under physiological conditions, we have engineered the ovarian cancer cell line, HM-1/luc, in mice. This cell stably expresses firefly luciferase and produces light that can be detected using an in vivo imaging system (IVIS). Parental HM-1 cells cause severe carcinomatous peritonitis to B6C3F1 mice, but not to C57BL6 mice. Established HM-1/luc cells showed pathologically similar findings to HM-1 cells. HM-1/luc cells were injected into the peritoneal cavity of B6C3F1 mice and IVIS 2000 was conducted weekly after inoculation to monitor intra-peritoneal tumor growth. The mice were divided into three groups: non-CDDP-treated (control) and CDDP-treated (0.2 and 0.4 mg). A disease-suppressive effect of the CDDP was reflected by the significantly prolonged survival of the CDDP-treated mice (control 23 +/- 1.9 days, CDDP 0.2 mg 29.6 +/- 2.9 days; p < 0.05); the total photon and area of flux were decreased. The optical imaging of intraperitoneal tumors via in vivo bioluminescence is effective for noninvasive monitoring and semi-quantitative analysis. Our syngeneic mouse model has the relevant clinical features of ovarian cancer, which makes it a useful model for developing new ovarian cancer therapies.

To design an ideal hydrogen ( H ) storage material, the understanding of the interaction between a host material and hydrogen is essential. The strength of the interaction determines the enthalpy and activation energy for H hopping. To obtain those physical quantities by utilizing first principle method, the crystal structure should be elucidated. We focused on Vanadium ( V ) as a representative of BCC (body-centered-cubic) type of hydrogen storage materials. The feature of BCC type storage material is characterized by the existence of β phase. We investigated the crystal and electronic structural changes with various H concentration in V . Without taking vibrational contribution into account, H atoms prefer to locate at tetrahedral sites. While taking the contribution into account, β phase can be the stable structure at VH composition.

We created a protein library consisting of 647 Arabidopsis transcription factors (TFs) using a wheat cell-free system. The quality of proteins in the library was checked by binding assay of bZIP family proteins. Screening of TFs binding to 5'-regulatory regions of FLC and LFY was conducted using the library, and MYB67 and GBF1 were found to be binding factors.

Matrix metalloproteinases (MMPs) have been implicated in a variety of normal and pathological conditions that involve matrix degradation and remodelling. We investigated the role of MMPs in acute graft-versus-host disease (aGVHD) in 29 patients who had undergone allogeneic haematopoietic stem cell transplantation. The present study showed that the serum levels of MMP-9, but not those of MMP-2, significantly correlated with the occurrence and severity of aGVHD. Moreover, immunohistochemical analysis of the cutaneous lesions of patients with aGVHD revealed an increased number of inflammatory cells positive for MMP-9. These results suggest that MMP-9 might play an important role in the pathogenesis of aGVHD.