The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks

BACKGROUND: Circadian rhythms are endogenous, self-sustained oscillations with approximately 24-hr rhythmicity that are manifested in various physiological and metabolic processes. The circadian organization of these processes in mammals is governed by the master oscillator within the suprachiasmatic nuclei (SCN) of the hypothalamus. Recent findings revealed that circadian oscillators exist in most organs, tissues, and even in immortalized cells, and that the oscillators in peripheral tissues are likely to be coordinated by SCN, the master oscillator. Some candidates for endogenous entrainment factors have sporadically been reported, however, their details remain mainly obscure. RESULTS: We developed the in vitro real-time oscillation monitoring system (IV-ROMS) by measuring the activity of luciferase coupled to the oscillatory gene promoter using photomultiplier tubes and applied this system to screen and identify factors able to influence circadian rhythmicity. Using this IV-ROMS as the primary screening of entrainment factors for circadian clocks, we identified 12 candidates as the potential entrainment factor in a total of 299 peptides and bioactive lipids. Among them, four candidates (endothelin-1, all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid) have already been reported as the entrainment factors in vivo and in vitro. We demonstrated that one of the novel candidates, 15-deoxy-Δ(12,14)-prostaglandin J(2 )(15d-PGJ(2)), a natural ligand of the peroxisome proliferator-activated receptor-γ (PPAR-γ), triggers the rhythmic expression of endogenous clock genes in NIH3T3 cells. Furthermore, we showed that 15d-PGJ(2 )transiently induces Cry1, Cry2, and Rorα mRNA expressions and that 15d-PGJ(2)-induced entrainment signaling pathway is PPAR-γ – and MAPKs (ERK, JNK, p38MAPK)-independent. CONCLUSION: Here, we identified 15d-PGJ(2 )as an entrainment factor in vitro. Using our developed IV-ROMS to screen 299 compounds, we found eight novel and four known molecules to be potential entrainment factors for circadian clocks, indicating that this assay system is a powerful and useful tool in initial screenings

THE INCIDENCE OF PEPTIC ULCER SURGERY BEFORE AND AFTER THE INTRODUCTION OF H2-RECEPTOR ANTAGONISTS

Since the introduction of H2-receptor antagonists, the incidence of ulcer surgery has decreased markedly. Based on the number of patients who underwent ulcer surgery and upper gastrointestinal endoscopy in our hospital, the number of operations for peptic ulcer disease has decreased, although the number of peptic ulcer patients diagnosed by endoscopy has increased after the introduction of cimetidine (the first H2-receptor antagonist in Japan). The decreasing rate of surgical therapy before and after the administration of H2-receptor antagonists was 49.1%. The number of emergency operations has also decreased among ulcer patients diagnosed by endoscopy although the number of perforated and bleeding ulcer patients has increased. It is also reported that the most common operative procedure for both gastric and duodenal ulcer was distal gastrectomy reconstructed by gastroduodenostomy (Billroth Ⅰ)

Over 10 years follow-up of Coats’ disease in adulthood

Coats’ disease diagnosed in adulthood is rare; therefore, the treatment options and longer clinical course are not well established. We report on two cases of adult onset Coats’ disease, which have been observed for more than 10 years after conventional treatment. In the first case, a 76-year-old man with 9 years of diabetic retinopathy noticed a visual field defect in his left eye. Yellowish subretinal exudation with serous retinal detachment in his superior peripheral retina, and telangiectatic vessels with fluorescein leakage, numerous microaneurysms, and areas of capillary nonperfusion observed in a fluorescein angiography indicated adult Coats’ disease, and retinal photocoagulation was applied. Within 1 year, subretinal exudation was regressed and visual acuity was improved from 20/50 to 20/20, and was maintained for the next 11 years. In the second case, a 71-year-old man presented with decreased vision in his right eye. The fundus of his right eye showed multiple telangiectasic vessels and subretinal exudates extended to the fovea, which is diagnosed as adult Coats’ disease. Despite retinal photocoagulation, an increase of exudation and an enlargement of retinal detachment was observed within 1 month, and subsequently, additional treatment of cryotherapy was performed. Two months after these therapies, the exudation was regressed without retinal detachment, and visual acuity was improved to 20/200 which was maintained for the next 10 years. Even with adult Coats’ disease, conventional therapies of retinal photocoagulation and cryotherapy are effective and are the initial choice for improving or maintaining visual function

A New Constraint on the Lyα\alpha Fraction of UV Very Bright Galaxies at Redshift 7

We study the extent to which very bright (-23.0 < MUV < -21.75) Lyman-break selected galaxies at redshifts z~7 display detectable Lya emission. To explore this issue, we have obtained follow-up optical spectroscopy of 9 z~7 galaxies from a parent sample of 24 z~7 galaxy candidates selected from the 1.65 sq.deg COSMOS-UltraVISTA and SXDS-UDS survey fields using the latest near-infrared public survey data, and new ultra-deep Subaru z'-band imaging (which we also present and describe in this paper). Our spectroscopy has yielded only one possible detection of Lya at z=7.168 with a rest-frame equivalent width EW_0 = 3.7 (+1.7/-1.1) Angstrom. The relative weakness of this line, combined with our failure to detect Lya emission from the other spectroscopic targets allows us to place a new upper limit on the prevalence of strong Lya emission at these redshifts. For conservative calculation and to facilitate comparison with previous studies at lower redshifts, we derive a 1-sigma upper limit on the fraction of UV bright galaxies at z~7 that display EW_0 > 50 Angstrom, which we estimate to be < 0.23. This result may indicate a weak trend where the fraction of strong Lya emitters ceases to rise, and possibly falls between z~6 and z~7. Our results also leave open the possibility that strong Lya may still be more prevalent in the brightest galaxies in the reionization era than their fainter counterparts. A larger spectroscopic sample of galaxies is required to derive a more reliable constraint on the neutral hydrogen fraction at z~7 based on the Lya fraction in the bright galaxies.Comment: 20 pages, 7 figures, accepted for publication in Ap

Continuing mind for primary care medicine as total family care mailing list (TFC-ML) group

There were historically two great doctors for primary care (PC) medicine in Japan. They are Dr. Shigeaki Hinohara and Dr. Yoshikazu Tasaka. Tasaka was always active in medical treatment, organizational management, postgraduate education, and information dissemination using the Internet, and started Total Family Care Mailing List (TFC-ML) in 1998. TFC-ML included medical information with his comments every day for long. Even after his death in 2007, TFC-ML activity has been continued by many voluntary PC physicians. His TFC mind has been transmitted to future PC physicians. His inspiration may often come to TFC members for better total family care