An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population.

Narcolepsy without cataplexy (NA w/o CA) (narcolepsy type 2) is a lifelong disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, but no cataplexy. In the present study, we examined the human leukocyte antigen HLA-DQB1 in 160 Japanese patients with NA w/o CA and 1,418 control subjects. Frequencies of DQB1*06:02 were significantly higher in patients with NA w/o CA compared with controls (allele frequency: 16.

Spatial and time-course thermodynamics during pulmonary vein isolation using the second-generation cryoballoon in a canine in vivo model.

Background: Thermodynamics in the left atrium-pulmonary vein (PV) junction, phrenic nerve, and esophagus during PV isolation (PVI) using the second-generation cryoballoon are not known.

Methods And Results: Twenty dogs underwent PVI using second-generation cryoballoon. Ablations were performed for ≤2 deliveries based on PVI without a bonus freeze.

Secretion of a truncated osteopetrosis-associated transmembrane protein 1 (OSTM1) mutant inhibits osteoclastogenesis through down-regulation of the B lymphocyte-induced maturation protein 1 (BLIMP1)-nuclear factor of activated T cells c1 (NFATc1) axis.

Genetic mutations in osteoclastogenic genes are closely associated with osteopetrotic bone diseases. Genetic defects in OSTM1 (osteopetrosis-associated transmembrane protein 1) cause autosomal recessive osteopetrosis in humans. In particular, OSTM1 mutations that exclude the transmembrane domain might lead to the production of a secreted form of truncated OSTM1.

Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment.

Almost all highly metastatic tumor cells possess high platelet aggregating abilities, thereby form large tumor cell-platelet aggregates in the microvasculature. Embolization of tumor cells in the microvasculature is considered to be the first step in metastasis to distant organs. We previously identified the platelet aggregation-inducing factor expressed on the surfaces of highly metastatic tumor cells and named as Aggrus.

Platelets promote osteosarcoma cell growth through activation of the platelet-derived growth factor receptor-Akt signaling axis.

The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation-inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor-platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma-platelet interactions induce the release of platelet-derived growth factor (PDGF) from platelets, which promotes the proliferation of osteosarcomas.

Alteration of strain ratio evaluated by transabdominal ultrasound elastography may predict the efficacy of preoperative chemoradiation performed for pancreatic ductal carcinoma: preliminary results.

Background/aim: We evaluated the usefulness of ultrasound-elastography (US-elastography) for prediction of therapy effect by measuring strain ratio (SR).

Methodology: Consecutive patients with resectable pancreatic ductal carcinoma who underwent US-elastography before and after neoadjuvant chemoradiation were included. Patients were classified into either response group or non-response group according to the histological evaluation of resected specimens.

A classification of congenital uterine anomalies predicting pregnancy outcomes.

Objective: To evaluate pregnancy outcomes in women with uterine anomalies by applying a method for diagnosing and classifying congenital uterine malformations.

Design: Retrospective study.

Setting: Tertiary care center.

Porphyromonas gingivalis-derived lysine gingipain enhances osteoclast differentiation induced by tumor necrosis factor-α and interleukin-1β but suppresses that by interleukin-17A: importance of proteolytic degradation of osteoprotegerin by lysine gingipain.

Periodontitis is a chronic inflammatory disease accompanied by alveolar bone resorption by osteoclasts. Porphyromonas gingivalis, an etiological agent for periodontitis, produces cysteine proteases called gingipains, which are classified based on their cleavage site specificity (i.e.

[A retrospective study of tegafur/uracil compared with cyclophosphamide, methotrexate, and fluorouracil as adjuvant chemotherapy in patients with node-negative, triple-negative breast cancer].

Japanese clinical trials of a tegafur/uracil(UFT)-based postoperative chemotherapy regimen compared with cyclophosphamide, methotrexate, and fluorouracil(CMF)treatment have shown that UFT is not inferior to CMF for the treatment of hormone receptor-positive breast cancer patients. However, the usefulness of UFT for hormone receptor-negative breast cancer, including the triple-negative subtype(hormone receptor-negative, human epidermal growth factor receptor 2 [HER2]-negative), is unknown. The aim of this retrospective study was to examine the effectiveness of postoperative, adjuvant UFT compared to CMF when these regimens were given to women with node-negative, triple-negative breast cancer.

Characteristic hydrolyzing of megalosaccharide by human salivary α-amylase and small intestinal enzymes, and its bioavailability in healthy subjects.

The digestibility of Megalosaccharide® (newly developed carbohydrate comprising α-1,4-glucosaccharide) was investigated in vitro and in vivo. Isomaltosyl-megalosaccharide® (IMS) and nigerosyl-megalosaccharide® (NMS) contain 20% and 50% of the megalosaccharide fraction (degree of polymerization (DP) 10-35), respectively. IMS was hydrolyzed readily by α-amylase to oligosaccharides (DP ≤ 7), and a small amount of glucose was produced from oligosaccharides by small intestinal enzymes (SIEs).

The astaxanthin-induced improvement in lipid metabolism during exercise is mediated by a PGC-1α increase in skeletal muscle.

Astaxanthin, a xanthophyll carotenoid, accelerates lipid utilization during aerobic exercise, although the underlying mechanism is unclear. The present study investigated the effect of astaxanthin intake on lipid metabolism associated with peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in mice. Mice were divided into 4 groups: sedentary, sedentary and astaxanthin-treated, exercised, and exercised and astaxanthin-treated.

γ-Secretase associated with lipid rafts: multiple interactive pathways in the stepwise processing of β-carboxyl-terminal fragment.

γ-Secretase generates amyloid β-protein (Aβ), a pathogenic molecule in Alzheimer disease, through the intramembrane cleavage of the β-carboxyl-terminal fragment (βCTF) of β-amyloid precursor protein. We previously showed the framework of the γ-secretase cleavage, i.e.

Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis.

Platelet aggregation-inducing factor Aggrus, also known as podoplanin, is associated with tumor malignancy by promoting hematogenous metastasis. Aggrus overexpression has been reported in some tumor tissues including lung, esophagus, head and neck and brain. We here found the frequent upregulation of aggrus mRNA in urinary bladder cancers using cancer tissue panels from various organs.

Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.

The platelet aggregation-inducing factor Aggrus, also known as podoplanin, is frequently upregulated in several types of tumors and enhances hematogenous metastasis by interacting with and activating the platelet receptor CLEC-2. Thus, Aggrus-CLEC-2 binding could be a therapeutic molecular mechanism for cancer therapy. We generated a new anti-human Aggrus monoclonal antibody, MS-1, that suppressed Aggrus-CLEC-2 binding, Aggrus-induced platelet aggregation, and Aggrus-mediated tumor metastasis.

Optimal strength and number of shocks at upper limit of vulnerability testing required to predict high defibrillation threshold without inducing ventricular fibrillation.

Background: The upper limit of vulnerability (ULV) closely correlates with the defibrillation threshold (DFT). The aim of this study was to establish the optimal protocol for using the ULV test to predict high DFT (>20 J) without inducing ventricular fibrillation (VF).

Methods And Results: The 10-J and 15-J ULV test with 3 coupling intervals (-20, 0, and +20 ms to the peak of T-wave) and the DFT test were performed in 96 patients receiving implantable cardioverter defibrillator.

Usefulness of full spine computed tomography in cases of high-energy trauma: a prospective study.

Introduction: At this hospital, computed tomography (CT) of the full spine is performed on all patients who have sustained high-energy trauma because spinal fractures can be overlooked by referring only to clinical findings and plain X-rays of the spine. The goal of this study is to prospectively detect the occurrence of spinal fractures in cases of high-energy trauma using full spine CT and to evaluate the usefulness of it.

Materials And Methods: Subjects were 179 patients (134 male, 45 female) who were deemed to have sustained high-energy trauma in the 21-month period starting in September 2007.

A minimally invasive surgery combining temporary percutaneous pedicle screw fixation without fusion and vertebroplasty with transpedicular intracorporeal hydroxyapatite blocks grafting for fresh thoracolumbar burst fractures: prospective study.

Background: The conventional surgical treatment for thoracolumbar burst fractures is physically invasive for the patient and also causes problems such as the sacrifice of healthy mobile segments to stabilize the fracture site. We performed a procedure for the treatment of fresh thoracolumbar burst fractures by combining percutaneous short pedicle screw fixation and vertebroplasty with transpedicular intracorporeal hydroxyapatite blocks grafting.

Methods: Patients with type A3 fresh thoracolumbar burst fractures with no or mild neurological symptoms were treated using temporary posterior fixation without fusion.

[Development and pharmacological effects of anti-RANKL monoclonal antibody drug denosumab].

Denosumab (called RANMARK(®) in Japan), an anti-bone resorptive drug, is a complete human type monoclonal antibody that targets the osteoclast differentiation factor receptor activator of NF-κB ligand (RANKL). Using advanced gene-engineering techniques, Amgen Inc. (USA) has developed the drug, and it is now utilized in Japan for treatment of cancerous bone lesions associated with multiple myeloma and bone metastasis.

Dabigatran in the peri-procedural period for radiofrequency ablation of atrial fibrillation: efficacy, safety, and impact on duration of hospital stay.

Purpose: Dabigatran is effective for both the prevention of stroke and bleeding in patients with atrial fibrillation (AF). However, the safety and efficacy of the use of dabigatran in the peri-procedural period for radiofrequency catheter ablation (RFCA) of AF is unknown. Therefore, the purpose of this study was to evaluate the safety and efficacy of dabigatran in the peri-procedural period for RFCA of AF and the duration of hospital stay.

Downregulation of carbonic anhydrase IX promotes Col10a1 expression in chondrocytes.

Carbonic anhydrase (CA) IX is a transmembrane isozyme of CAs that catalyzes reversible hydration of CO(2). While it is known that CA IX is distributed in human embryonic chondrocytes, its role in chondrocyte differentiation has not been reported. In the present study, we found that Car9 mRNA and CA IX were expressed in proliferating but not hypertrophic chondrocytes.

γ-Secretase-Dependent Proteolysis of Transmembrane Domain of Amyloid Precursor Protein: Successive Tri- and Tetrapeptide Release in Amyloid β-Protein Production.

γ-Secretase cleaves the carboxyl-terminal fragment (βCTF) of APP not only in the middle of the transmembrane domain (γ-cleavage), but also at sites close to the membrane/cytoplasm boundary (ε-cleavage), to produce the amyloid β protein (Aβ) and the APP intracellular domain (AICD), respectively. The AICD49-99 and AICD50-99 species were identified as counterparts of the long Aβ species Aβ48 and Aβ49, respectively. We found that Aβ40 and AICD50-99 were the predominant species in cells expressing wild-type APP and presenilin, whereas the production of Aβ42 and AICD49-99 was enhanced in cells expressing familial Alzheimer's disease mutants of APP and presenilin.

γ-secretase modulators and presenilin 1 mutants act differently on presenilin/γ-secretase function to cleave Aβ42 and Aβ43.

Deciphering the mechanism by which the relative Aβ42(43) to total Aβ ratio is regulated is central to understanding Alzheimer disease (AD) etiology; however, the mechanisms underlying changes in the Aβ42(43) ratio caused by familial mutations and γ-secretase modulators (GSMs) are unclear. Here, we show in vitro and in living cells that presenilin (PS)/γ-secretase cleaves Aβ42 into Aβ38, and Aβ43 into Aβ40 or Aβ38. Approximately 40% of Aβ38 is derived from Aβ43.

Octacalcium phosphate suppresses chondrogenic differentiation of ATDC5 cells.

Implantation of octacalcium phosphate (OCP), a hydroxyapatite precursor, has been reported to induce chondrogenesis in vivo. In this study, we examined the effects of OCP on the chondrogenic differentiation of mouse chondroblastic ATDC5 cells in vitro. Contrary to our expectation, chondrogenic differentiation of ATDC5 cells evaluated by the mRNA expression of Col2a1, Acan and Col10a1 was suppressed by OCP.