Circadian production of melatonin in cartilage modifies rhythmic gene expression

Endochondral ossification, including bone growth and other metabolic events, is regulated by circadian rhythms. Herein, we provide evidence that melatonin has a direct effect on the circadian rhythm of chondrocytes. We detected mRNA expression of the genes which encode the melatonin-synthesizing enzymes AANAT (arylalkylamine N-acetyltransferase) and HIOMT (hydroxyindole O-methyltransferase), as well as the melatonin receptors MT1 and MT2 in mouse primary chondrocytes and cartilage. Production of melatonin was confirmed by mass spectrometric analysis of primary rat and chick chondrocytes. Addition of melatonin to primary mouse chondrocytes caused enhanced cell growth and increased expression of Col2a1, Aggrecan, and Sox9, but inhibited Col10a1 expression in primary BALB/c mouse chondrocytes. Addition of luzindole, an MT1 and MT2 antagonist, abolished these effects. These data indicate that chondrocytes produce melatonin, which regulates cartilage growth and maturation via the MT1 and MT2 receptors. Kinetic analysis showed that melatonin caused rapid upregulation of Aanat, Mt1, Mt2, and Pthrp expression, followed by Sox9 and Ihh. Furthermore, expression of the clock gene Bmal1 was induced, while that of Per1 was downregulated. Chronobiological analysis of synchronized C3H mouse chondrocytes revealed that melatonin induced the cyclic expression of Aanat and modified the cyclic rhythm of Bmal1, Mt1, and Mt2. In contrast, Mt1 and Mt2 showed different rhythms from Bmal1 and Aanat, indicating the existence of different regulatory genes. Our results indicate that exogenous and endogenous melatonin work in synergy in chondrocytes to adjust rhythmic expression to the central suprachiasmatic nucleus clock

Search for VHE gamma rays from SS433/W50 with the CANGAROO-II telescope

SS433, located at the center of the supernova remnant W50, is a close proximity binary system consisting of a compact star and a normal star. Jets of material are directed outwards from the vicinity of the compact star symmetrically to the east and west

Search for TeV gamma-rays from SN 1987A in 2001

We searched for TeV gamma-rays from the remnant of SN 1987A around 5400 days after the supernova. The observations were carried out in 2001, from November 16 to December 11, using the CANGAROO-II Imaging Atmospheric Cherenkov Telescope. In total, 708 minutes of ON- and 1019 minutes of OFF-source data were obtained under good conditions. The detection threshold was estimated to be 1 TeV, due to the mean zenith angle of 39$^\circ$. The upper limits for the gamma-ray flux were obtained and compared with the previous observations and theoretical models. The observations indicate that the gamma-ray luminosity is lower than $1\times 10^{37}$ erg s$^{-1}$ at $\sim 10$ TeV.Comment: 8 pages, 3 figures, submitted for publication, style file adde

Detection of diffuse TeV gamma-ray emission from the nearby starburst galaxy NGC 253

We report the TeV gamma-ray observations of the nearby normal spiral galaxy NGC 253. At a distance of $\sim$2.5 Mpc, NGC 253 is one of the nearest starburst galaxies. This relative closeness, coupled with the high star formation rate in the galaxy, make it a good candidate TeV gamma-ray source. Observations were carried out in 2000 and 2001 with the CANGAROO-II 10 m imaging atmospheric Cerenkov telescope. TeV gamma-ray emission is detected at the $\sim 11\sigma$ level with a flux of $(7.8 \pm 2.5)\times 10^{-12} {\rm cm}^{-2} {\rm sec}^{-1}$ at energies $>$0.5 TeV. The data indicate that the emission region is broader than the point spread function of our telescope.Comment: 4 pages, double colomn, 3 figures, aa.cl

Quantification of Cell Migration and Invasion, and Their Association with Periostin in Anaplastic Thyroid Cancer, Using a Real-time Cell Analyzer

Anaplastic thyroid cancer (ATC) is known to be a highly malignant cancer of the thyroid with a high mortality rate. In a previous study, we used real-time cell analysis (RTCA) to analyze cell migration and invasion of oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth. In the present study, we investigated cell migration and invasion of ATC using RTCA, as well as their association with periostin, matrix metalloproteinases (MMPs), and integrins. Experiments were performed on TCO-1 and HTC/C3 cells, which are human ATC cell lines. OSCC cell lines were used for comparison. Using the cell analysis system, cell migration was assessed on fibronectin-coated CIM-Plates, whereas invasion was assessed on fibronectin- and matrigel-coated CIM-Plates. SCC-4 cells exhibited high cell migration and invasion activity compared with other OSCC cell lines. TCO-1 cells exhibited equivalent cell invasion but stronger migration than SCC-4 cells. Although TCO-1 cells had strong invasive activity, they did not express MMP-9, unlike SCC-4 cells. Conversely, periostin expression was high in TCO-1 cells. Therefore, periostin expression appears to be associated with the cell migration and invasion activity of ATC. The RTCA system will be useful for the analysis of the metastatic characteristics of ATC in head and neck cancer

Evidence of TeV gamma-ray emission from the nearby starburst galaxy NGC 253

TeV gamma-rays were recently detected from the nearby normal spiral galaxy NGC 253 (Itoh et al., 2002). Observations to detect the Cherenkov light images initiated by gamma-rays from the direction of NGC 253 were carried out in 2000 and 2001 over a total period of $\sim$150 hours. The orientation of images in gamma-ray--like events is not consistent with emission from a point source, and the emission region corresponds to a size greater than 10 kpc in radius. Here, detailed descriptions of the analysis procedures and techniques are given.Comment: 16 pages, 27 figures, aa.cl

Case Report: Unresectable pulmonary metastases of a giant cell tumor of bone treated with denosumab: a case report and review of literature

Giant cell tumors of bone (GCTB) sometimes metastasize to distant organs. In this case report, we present pulmonary metastases of GCTB mimicking malignancies. A 49-year-old man underwent two surgical treatments for a GCTB of the right proximal radius. At the time of the second surgery, no lesions were observed on chest radiography. Three years after surgery, the patient presented with cough and dyspnea, and chest radiography and computed tomography (CT) revealed multiple lung nodules. Positron emission tomography/CT revealed a high accumulation of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in multiple lesions. Based on the rapid growth and accumulation of 18F-FDG, a metastatic malignant tumor was suspected. CT-guided needle biopsy was performed, and the histology showed proliferation of spindle cells and multinuclear giant cells without malignant changes. Denosumab was administered because multiple lung lesions were unresectable. One month after denosumab treatment, CT showed marked shrinkage of the lesions, and the symptoms significantly improved. Eighteen months after the initial treatment with denosumab, the patient had no symptoms or tumor growth. Although its long-term efficacy and safety remain unclear, denosumab may be a treatment option for patients with unresectable pulmonary GCTB

Prolonged Tachycardia with Higher Heart Rate Is Associated with Higher ICU and In-hospital Mortality

Tachycardia is common in intensive care units (ICUs). It is unknown whether tachycardia or prolonged tachycardia affects patient outcomes. We investigated the association between tachycardia and mortality in critically ill patients. This retrospective cohort study’s primary outcome was patient mortality in the ICU and the hospital. We stratified the patients (n=476) by heart rate (HR) as LowHR, MediumHR, and HighHR groups. We also stratified them by their durations of HR >100 (prolonged HR; tachycardia): MildT, ModerateT, and SevereT groups. We determined the six groups’ mortality. The ICU mortality rates of the LowHR, MediumHR, and HighHR groups were 1.0%, 1.5%, and 7.9%, respectively; significantly higher in the HighHR vs. LowHR group. The in-hospital mortality rates of these groups were 1%, 4.5%, and 14.6%, respectively; significantly higher in the HighHR vs. LowHR group. The ICU mortality rates of the MildT, ModerateT, and SevereT groups were 0.9%, 5.6%, and 57.1%, respectively. The mortality of the HRT=0 (i.e., all HR ≤ 100) patients was 0%. The in-hospital mortality rates of the MildT, ModerateT, and SevereT groups were 1.8%, 16.7%, and 85.7%, respectively; that of the HRT=0 patients was 0.5%. Both higher HR and prolonged tachycardia were associated with poor outcomes

Detection of Gamma-rays around 1TeV from RX J0852.0-4622 by CANGAROO-II

We have detected gamma-ray emission at the 6sigma level at energies greater than 500GeV from the supernova remnant RX J0852.0-4622 (G266.2-1.2) using the CANGAROO-II Imaging Atmospheric Cherenkov Telescope (IACT). The flux was 0.12 times of that of Crab at 1TeV. The signal centroid is consistent with the peak of the X-ray emission in the north-west rim of the remnant.Comment: 12pages, 4figures, to be published in ApJ

Search for VHE gamma rays from SS433/W50 with the CANGAROO-II telescope

SS433, located at the center of the supernova remnant W50, is a close proximity binary system consisting of a compact star and a normal star. Jets of material are directed outwards from the vicinity of the compact star symmetrically to the east and west. Non-thermal hard X-ray emission is detected from lobes lying on both sides. Shock accelerated electrons are expected to generate sub-TeV gamma rays through the inverse-Compton process in the lobes. Observations of the western X-ray lobe region of SS433/W50 system have been performed to detect sub-TeV gamma-rays using the 10m CANGAROO-II telescope in August and September, 2001, and July and September, 2002. The total observation times are 85.2 hours for ON source, and 80.8 hours for OFF source data. No significant excess of sub-TeV gamma rays has been found at 3 regions of the western X-ray lobe of SS433/W50 system. We have derived 99% confidence level upper limits to the fluxes of gamma rays and have set constraints on the strengths of the magnetic fields assuming the synchrotron/inverse-Compton model for the wide energy range of photon spectrum from radio to TeV. The derived lower limits are 4.3 microgauss for the center of the brightest X-ray emission region and 6.3 microgauss for the far end from SS433 in the western X-ray lobe. In addition, we suggest that the spot-like X-ray emission may provide a major contribution to the hardest X-ray spectrum in the lobe.Comment: 7 pages, 8 figures, to be published in Astroparticle Physic