A missense variant in PER2 is associated with delayed sleep-wake phase disorder in a Japanese population.

Delayed sleep-wake phase disorder (DSWPD) is a subtype of circadian rhythm sleep-wake disorders, and is characterized by an inability to fall asleep until late at night and wake up at a socially acceptable time in the morning. The study aim was to identify low-frequency nonsense and missense variants that are associated with DSWPD. Candidate variants in circadian rhythm-related genes were extracted by integration of genetic variation databases and in silico assessment.

Lack of association between variable number tandem repeat and circadian rhythm sleep-wake disorders.

Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by disturbed sleep-wake patterns. We genotyped a variable number tandem repeat (VNTR) in 248 CRSWD individuals and 925 controls and found no significant association between the VNTR and CRSWDs or morningness-eveningness (diurnal) preferences in the Japanese population. Although the VNTR has been associated with circadian and sleep phenotypes in some other populations, the polymorphism may not be a universal genetic marker.

Regulation of molecular clock oscillations and phagocytic activity via muscarinic Ca signaling in human retinal pigment epithelial cells.

Vertebrate eyes are known to contain circadian clocks, however, the intracellular mechanisms regulating the retinal clockwork remain largely unknown. To address this, we generated a cell line (hRPE-YC) from human retinal pigmental epithelium, which stably co-expressed reporters for molecular clock oscillations (Bmal1-luciferase) and intracellular Ca concentrations (YC3.6).

[The Outpatient Clinic and Rehabilitation Program Specialized in Adult Developmental Disorders].

The rehabilitation program has been conducted at our psychiatric clinic for depressive patients who are absent from work, with the aim of assisting them to return to work. We have noticed that a substantial number of the patients have traits of developmental disorders, which contribute to chronicity and/or recurrence of depression. Therefore, we have recently created a new rehabilitation program in addition to the specialty outpatient clinic and peer support group.

Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder.

A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT).

Analysis of the molecular pathophysiology of sleep disorders relevant to a disturbed biological clock.

Genetic studies have revealed several clock gene variations/mutations involved in the manifestation of sleep disorders or interindividual differences in sleep-wake patterns, but only part of the genetic risk can be explained by the gene variations/mutations identified to date. Recent progress in research into circadian rhythm generation has provided efficient tools for eliciting the molecular basis of clock-relevant sleep disorders, complementing traditional genetic analysis. While the human master clock resides in the suprachiasmatic nucleus of the hypothalamus (central clock), peripheral tissue cells also generate self-sustained circadian oscillations of clock gene expression (peripheral clock), enabling estimation of individual human clock properties through a single collection of skin fibroblasts or venous blood cells.

Plasma atrial natriuretic peptide is an early diagnosis and disease severity marker of myxomatous mitral valve disease in dogs.

The aim of this study was to retrospectively assess the clinical usefulness of plasma atrial natriuretic peptide (ANP) concentrations for determining the severity of myxomatous mitral valve disease (MMVD) in dogs. Plasma ANP levels were found to be significantly higher in dogs with MMVD compared to healthy dogs, and plasma ANP levels increased significantly in dogs with progressive heart failure. In dogs with MMVD, stepwise regression analysis revealed that the left atrium/aorta ratio and fractional shortening could be used to predict the plasma ANP concentration.

Mitral valve repair under cardiopulmonary bypass in small-breed dogs: 48 cases (2006-2009).

Objective: To determine whether mitral valve repair (MVR) under cardiopulmonary bypass would be an effective treatment for mitral regurgitation in small-breed dogs.

Design: Retrospective case series.

Animals: 48 small-breed dogs (body weight, 1.

An association analysis of Per2 with panic disorder in the Japanese population.

Panic disorder (PD) is a severe and chronic psychiatric disorder, with genetic components underlying in its etiology. The PERIOD2 (Per2) gene has been reported to be associated with familial advanced sleep phase syndrome. Considering the high frequency of sleep disturbance in PD, Per2 may be a candidate gene for PD.

Surgical closure of an atrial septal defect using cardiopulmonary bypass in a cat.

Objective: To describe surgical repair of a large atrial septal defect (ASD) in a cat.

Study Design: Clinical report.

Animal: A 3-year-old, 3.

Surgical repair of a complete endocardial cushion defect in a dog.

Objective: To describe surgical repair of a complete endocardial cushion defect (ECD) in a dog.

Study Design: Clinical report.

Animal: A 5-month-old, 9.

Self-sustained circadian rhythm in cultured human mononuclear cells isolated from peripheral blood.

Disturbed circadian rhythmicity is associated with human diseases such as sleep and mood disorders. However, study of human endogenous circadian rhythm is laborious and time-consuming, which hampers the elucidation of diseases. It has been reported that peripheral tissues exhibit circadian rhythmicity as the suprachiasmatic nucleus-the center of the biological clock.

Introduction of tau mutation into cultured Rat1-R12 cells by gene targeting, using recombinant adeno-associated virus vector.

We aim to develop a cultured cell model, to serve as a system with which the altered circadian phenotypes produced by the clock gene variations could be studied in vitro. Tau mutation, which shortens the circadian period of hamsters and mice, was introduced into the CK1epsilon locus of cultured Rat1-R12 cells by gene targeting mediated by a recombinant adeno-associated virus (rAAV) vector. After transduction of Rat1-R12 cells with rAAV, about 0.

Continuous observation of rabbit preimplantation embryos in vitro by using a culture device connected to a microscope.

We developed a compact culture device that maintains developing embryos in vitro under constant temperature and CO(2) concentration. Using this device, we cultured rabbit embryos from the pronuclear stage to the hatched blastocyst stage and recorded their development digitally for 7 d. Recorded images were converted to a movie, and the developmental movement of individual embryos was analyzed.

The influence of gender on cardiac fibrosis induced by sympathetic stimulation.

We examined the influence of sex steroids on cardiac effects of sympathetic agents in mice. The mice were divided into four groups: males, neutered males (N-males), females, and neutered females (N-females). Dobutamine (DOB; 2.

Establishment of human cell lines showing circadian rhythms of bioluminescence.

We have established human retinal pigment epithelial cell lines stably expressing the luciferase gene, driven by the human Bmal1 promoter, to obtain human-derived cells that show circadian rhythms of bioluminescence after dexamethasone treatment. The average circadian period of bioluminescence for the obtained clones was 24.07+/-0.

Evaluation of the renin-angiotensin system in cardiac tissues of cats with pressure-overload cardiac hypertrophy.

Objective: To clarify regulation of the renin-angiotensin (RA) system in cardiac tissues by measuring angiotensin-converting enzyme (ACE) and chymase activities in cats with pressure-overload cardiac hypertrophy.

Animals: 13 adult cats.

Procedures: Pressure-overload cardiac hypertrophy was induced by coarctation of the base of the ascending aorta in 6 cats, and 7 cats served as untreated control animals.

[Functional polymorphisms in clock genes and circadian rhythm sleep disorders].

Polymorphisms in clock genes induce circadian rhythm sleep disorders. Mutations in Per2 gene (S662G) or Casein Kinasel delta (CK16) gene (T44A) cause Familial advanced sleep phase syndrome. Missense polymorphisms in Per3 (V647G) and CK1e (S408N) genes increase or decrease the risk of developing delayed sleep phase syndrome.

Changes in the myocardial performance index during dobutamine administration in anesthetized cats.

Objective: To investigate the relationship between myocardial performance index (MPI; also known as the Tei index) and cardiac function in anesthetized cats administered dobutamine.

Animals: 6 adult cats.

Procedures: Cats were anesthetized by administration of propofol (6 mg/kg, IV), and anesthesia was maintained by administration of isoflurane.

Circadian rhythms in the CNS and peripheral clock disorders: human sleep disorders and clock genes.

Genetic analyses of circadian rhythm sleep disorders (CRSD), such as familial advanced sleep phase syndrome (ASPS) and delayed sleep phase syndrome (DSPS), and morningness-eveningness revealed the relationship between variations in clock genes and diurnal change in human behaviors. Variations such as T3111C in the Clock gene are reportedly associated with morningness-eveningness. Two of the pedigrees of familial ASPS (FASPS) are caused by mutations in clock genes: the S662G mutation in the Per2 gene or the T44A mutation in the casein kinase 1 delta (CK1delta) gene, although these mutations are not found in other pedigrees of FASPS.

Short term change of urinary N-acetyl-beta-D-glucosaminidase in reduced kidney mass with renal artery ligation.

The aim of the present study was to evaluate short term urinary NAG levels in a model of reduced kidney mass. The half and quarter kidney mass were made from ligation of the renal artery. Both groups decreased in the level of excreted NAG on day 1 and 2 after operation.

No association between the CNTF null mutation and schizophrenia or personality.

The ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that plays a critical role in neurodevelopment. On the basis of neurodevelopmental hypothesis, the CNTF gene has been a candidate locus for schizophrenia. Several studies have investigated the association between the null mutation of the gene and schizophrenia, however, with inconsistent results.

Effects of enalapril in cats with pressure overload-induced left ventricular hypertrophy.

In order to evaluate the effect of enalapril on haemodynamics and renal function in a pressure overload model, we prepared eight feline models of left ventricular hypertrophy (LVH) by banding of the aortic arch. The LVH cats were assigned to the placebo group or the enalapril group (0.5 mg/kg, PO, sid) 3 months following surgery, and each received its respective drug for 4 weeks.