Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice.

Regulators of G protein signaling (RGS) are a multi-functional protein family, which functions in part as GTPase-activating proteins (GAPs) of G protein α-subunits to terminate G protein signaling. Previous studies have demonstrated that the Rgs16 transcripts exhibit robust circadian rhythms both in the suprachiasmatic nucleus (SCN), the master circadian light-entrainable oscillator (LEO) of the hypothalamus, and in the liver. To investigate the role of RGS16 in the circadian clock in vivo, we generated two independent transgenic mouse lines using lentiviral vectors expressing short hairpin RNA (shRNA) targeting the Rgs16 mRNA.

Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals.

Aims/hypothesis: In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes.

Methods: We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations.

Reconstruction of the first web in congenital thumb anomalies.

Reconstruction of the first web is an important technique for thumb adduction contracture accompanying congenital anomalies. Our previous cases have been reviewed here to evaluate and compare the indications, results, and problems for these two techniques. The angle formed by the first and second metacarpals (first-second metacarpal angle; 1-2 MCA) on the anterio-posterior (AP) view of the hand, with the thumb in maximum radial abduction, was measured from X-ray.

Surgical treatment of spontaneous posterior interosseous nerve palsy: a retrospective study of 50 cases.

We have reviewed 38 surgically treated cases of spontaneous posterior interosseous nerve palsy in 38 patients with a mean age of 43 years (13 to 68) in order to identify clinical factors associated with its prognosis. Interfascicular neurolysis was performed at a mean of 13 months (1 to 187) after the onset of symptoms. The mean follow-up was 21 months (5.

Costo-osteochondral graft for post-traumatic osteonecrosis of the radial head in an adolescent boy.

We present a case of post-traumatic osteonecrosis of the radial head in a 13-year-old boy which was treated with costo-osteochondral grafts. A satisfactory outcome was seen at a follow-up of two years and ten months. Although costo-osteochondral grafting has been used in the treatment of defects in articular cartilage, especially in the hand and the elbow, the extension of the technique to manage post-traumatic osteonecrosis of the radial head in a child has not previously been reported in the English language literature.

The trapezius-splitting approach: modifications for treating disorders and traumas occurring in the lateral supraspinatus fossa.

Background: Disorders or traumas requiring surgery other than suprascapular entrapment neuropathy that occur in the lateral supraspinatus fossa are decidedly uncommon. Because a wider operative field is necessary for treating these disorders, we have applied a trapezius-splitting approach with some modifications.

Methods: The procedure comprises a saber cut incision along with trapezius-splitting of 5 cm to 6 cm proximally from the position coinciding with the posterior margin of the acromioclavicular joint.

Clinical and genetic characteristics of patients with autoimmune thyroid disease with anti-islet autoimmunity.

In contrast to the large number of studies on autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus, little is known about the anti-islet autoimmune status in patients with autoimmune thyroid diseases (AITDs). We therefore studied the anti-islet autoimmune status in patients with AITD and the clinical and genetic characteristics of AITD patients with anti-islet autoimmunity. The positivity and titer of glutamic acid decarboxylase antibody (GAD Ab) were studied in 866 Japanese patients with AITD (546 with Graves disease and 320 with Hashimoto thyroiditis), 221 patients with thyroid disease of nonautoimmune origin, and 282 control subjects.

Nuclear hormone retinoid X receptor (RXR) negatively regulates the glucose-stimulated insulin secretion of pancreatic ß-cells.

Objective: Retinoid X receptors (RXRs) are members of the nuclear hormone receptor superfamily and are thought to be key regulators in differentiation, cellular growth, and gene expression. Although several experiments using pancreatic β-cell lines have shown that the ligands of nuclear hormone receptors modulate insulin secretion, it is not clear whether RXRs have any role in insulin secretion.

Research Design And Methods: To elucidate the function of RXRs in pancreatic β-cells, we generated a double-transgenic mouse in which a dominant-negative form of RXRβ was inducibly expressed in pancreatic β-cells using the Tet-On system.

Efficacy and safety of metformin for treatment of type 2 diabetes in elderly Japanese patients.

Aim: The maximum dosage of metformin allowed for clinical use in Japan is much less than half that in Western countries, making it difficult to apply the results of clinical trials in Western countries to Japanese patients. In particular, the efficacy and safety of metformin in elderly patients are largely unknown.

Methods: Among 1508 patients who were newly prescribed metformin at our hospital from 2000-2006, patients with sufficient clinical data were retrospectively studied for the safety (n=1132) and efficacy (n=568) of the drug.

Insulin transactivator MafA regulates intrathymic expression of insulin and affects susceptibility to type 1 diabetes.

Objective: Tissue-specific self-antigens are ectopically expressed within the thymus and play an important role in the induction of central tolerance. Insulin is expressed in both pancreatic islets and the thymus and is considered to be the primary antigen for type 1 diabetes. Here, we report the role of the insulin transactivator MafA in the expression of insulin in the thymus and susceptibility to type 1 diabetes.

Supracondylar osteotomy of the humerus to correct cubitus varus: do both internal rotation and extension deformities need to be corrected?

Background: A variety of osteotomies has been proposed to correct posttraumatic cubitus varus deformity as well as any associated hyperextension and/or rotational deformities. However, lateral closing-wedge osteotomy and step-cut osteotomy, both of which have been used extensively with satisfactory outcomes, correct only in the coronal plane. To date, no direct comparison has been made between three-dimensional and simple coronal plane osteotomies.

3-Cyano-6-(5-methyl-3-pyrazoloamino)pyridines: selective Aurora A kinase inhibitors.

A new class of Aurora A kinase inhibitor was created by transforming 4-(5-methyl-3-pyrazoloamino)pyrimidine moiety of VX-680 to 3-cyano-6-(5-methyl-3pyrazoloamino)pyridine. Compound 6 exhibited a potent Aurora A kinase inhibitory activity, excellent selectivity to Aurora B kinase and other 60 kinases, good cell permeability and good PK profile. Therefore compound 6 was effective in antitumor mice model at a dose of 30 mg/kg po qd without decrease of body weight.

Involvement of microsomal triglyceride transfer protein in nonalcoholic steatohepatitis in novel spontaneous mouse model.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is currently recognized as a global health issue and encompasses a wide spectrum of entities, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). The lack of a spontaneous animal model of NASH, however, has hampered basic research in this field.

Methods: We examined the hepatic lesions in the inbred Fatty Liver Shionogi (FLS) mouse, which exhibits type 2 diabetes, and investigated the molecular mechanism leading to NAFLD/NASH.

Direct evidence for susceptibility genes for type 2 diabetes on mouse chromosomes 11 and 14.

Aims/hypothesis: Diabetogenic loci for type 2 diabetes have been mapped to mouse chromosome (Chr) 11 and 14 in the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of type 2 diabetes. We aimed to obtain direct evidence of these genes on each chromosome and to clarify their function and interaction in conferring susceptibility to type 2 diabetes.

Methods: We established three consomic strains homozygous for diabetogenic NSY-Chr11, NSY-Chr14 or both on the control C3H background (C3H-11(NSY), C3H-14(NSY) and C3H-11(NSY)14(NSY), respectively), and monitored diabetes-related phenotypes longitudinally.

Effect of shortening deformity of the clavicle on scapular kinematics: a cadaveric study.

Background: In some short malunion cases, midshaft clavicular fractures are reported to result in unsatisfactory clinical outcomes. Shortening deformity of the clavicle could change the anatomical alignment of the shoulder girdle and is surmised to affect shoulder kinematics on arm movements. Nevertheless, no report has ever referred to documented changes.

Phylloid hypermelanosis and melanocytic nevi with aggregated and disfigured melanosomes: causal relationship between phylloid pigment distribution and chromosome 13 abnormalities.

The mosaic pattern of phylloid hypomelanosis is mostly associated with chromosome 13 abnormalities. Recently, 1 case of hypermelanosis in a phylloid pattern has been described. We describe a 29-year-old Japanese male with mental retardation, phylloid hypermelanosis and histopathologically and ultrastructurally peculiar melanocytic nevi, which were associated with 3 aberrant chromosome 13 cell lines.

Inhibition of STAT1 accelerates bone fracture healing.

Skeletal fracture healing involves a variety of cellular and molecular events; however, the mechanisms behind these processes are not fully understood. In the current study, we investigated the potential involvement of the signal transducer and activator of transcription 1 (STAT1), a critical regulator for both osteoclastogenesis and osteoblast differentiation, in skeletal fracture healing. We used a fracture model and a cortical defect model in mice, and found that fracture callus remodeling and membranous ossification are highly accelerated in STAT1-deficient mice.

Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations.

Aims/hypothesis: To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations.

Methods: We genotyped five common variants previously reported in Europeans: rs1799884 (GCK), rs780094 (GCKR), rs560887 (G6PC2-ABCB11) and both rs1387153 and rs10830963 (MTNR1B) in the general Japanese (n = 4,813) and Sri Lankan (n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples.

Impact of Previous PCI on Hospital Mortality After Off-Pump Coronary Artery Bypass Grafting in Diabetic Patients With Multivessel Disease.

Objective: : Because percutaneous coronary intervention (PCI) has been performed excessively, many patients initially managed with PCI are being referred for coronary artery bypass grafting (CABG). The purpose of this study was to assess the impact of previous PCI on surgical mortality after off-pump CABG in diabetic patients with multivessel disease.

Methods: : Between January 2002 and April 2008, 595 consecutive patients (99.

Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice.

Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG), a decoy receptor of RANKL, maintain bone mass by regulating the differentiation of osteoclasts, which are bone-resorbing cells. Endochondral bone ossification and bone fracture healing involve cartilage resorption, a less well-understood process that is needed for replacement of cartilage by bone. Here we describe the role of OPG produced by chondrocytes in chondroclastogenesis.

Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset.

Aim/hypothesis: We sought to clarify similarities and differences in the contribution of HLA to genetic susceptibility to three subtypes of type 1 diabetes: acute-onset, fulminant and slowly progressive.

Methods: We genotyped 545 Japanese patients with type 1 diabetes (338 acute-onset, 80 fulminant, 127 slowly progressive) and 396 control participants at HLA-DRB1, -DQB1, -A, -B and -C, and at 101 candidate single nucleotide polymorphisms (SNPs) in an 8.5 Mb region of the extended HLA.

Low-dose vasopressin infusion therapy for refractory hypotension in ELBW infants.

Background: Severe hypotension in infants, especially in preterm infants, is associated with poor neurological outcome and high mortality. In adults, low-dose vasopressin (arginine vasopressin: AVP) infusion therapy has been effective for treating hypotension that is refractory to vasopressors and inotropes.

Methods: The effects of AVP infusion therapy for refractory hypotension were retrospectively evaluated in extremely low-birthweight infants.

Defining impairment and treatment of subacute and chronic fractures of the coracoid process.

Background: Concerning subacute and chronic coracoid fractures, the details of these disorders and its consequent treatment methods have not yet been established.

Methods: Fifteen patients who received treatment at 23 weeks +/- 23 weeks after injury were followed up for 23 months +/- 10 months. There were 10 type I fractures and 5 type II fractures according to the classification proposed by Ogawa et al.

Computer simulation of humeral shaft fracture in throwing.

Hypothesis: Throwing fractures of the humerus are well known, but the exact mechanism of injury is not clear. It has been postulated that these may be stress fractures because the forces have not seemed sufficient to cause acute fractures while throwing.

Materials And Methods: Using finite element analysis, we reproduced fractures of the humerus using 3-dimensional models built from computed tomography images of 5 healthy volunteers.