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Author Yasuniwa, Y.; Izumi, H.; Wang, K.-Y.; Shimajiri, S.; Sasaguri, Y.; Kawai, K.; Kasai, H.; Shimada, T.; Miyake, K.; Kashiwagi, E.; Hirano, G.; Kidani, A.; Akiyama, M.; Han, B.; Wu, Y.; Ieiri, I.; Higuchi, S.; Kohno, K. url  doi
openurl 
  Title Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway Type Journal Article
  Year (down) 2010 Publication PloS one Abbreviated Journal PLoS One  
  Volume 5 Issue 12 Pages e15330  
  Keywords Animals; *Circadian Rhythm; Disease Progression; *Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms/*pathology; *Neovascularization, Pathologic; Nerve Tissue Proteins/metabolism; Skin/metabolism; Vascular Endothelial Growth Factor A/metabolism; Wnt Proteins/*metabolism; Oncogenesis  
  Abstract Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway.  
  Address Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:21203463; PMCID:PMC3009728 Approved no  
  Call Number IDA @ john @ Serial 162  
Permanent link to this record
 

 
Author Gooley, J.J.; Rajaratnam, S.M.W.; Brainard, G.C.; Kronauer, R.E.; Czeisler, C.A.; Lockley, S.W. url  doi
openurl 
  Title Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light Type Journal Article
  Year (down) 2010 Publication Science Translational Medicine Abbreviated Journal Sci Transl Med  
  Volume 2 Issue 31 Pages 31ra33  
  Keywords Adolescent; Adult; Circadian Rhythm/physiology/*radiation effects; Dose-Response Relationship, Radiation; Humans; Light; Melatonin/secretion; Photoperiod; Phototherapy; Retina/physiology/radiation effects; Retinal Cone Photoreceptor Cells/physiology/radiation effects; Retinal Ganglion Cells/physiology/radiation effects; Rod Opsins/physiology; Young Adult; blue light; light at night; melatonin; melanopsin; light therapy  
  Abstract In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.  
  Address Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1946-6234 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:20463367 Approved no  
  Call Number IDA @ john @ Serial 294  
Permanent link to this record
 

 
Author Brainard, G.C.; Sliney, D.; Hanifin, J.P.; Glickman, G.; Byrne, B.; Greeson, J.M.; Jasser, S.; Gerner, E.; Rollag, M.D. url  doi
openurl 
  Title Sensitivity of the human circadian system to short-wavelength (420-nm) light Type Journal Article
  Year (down) 2008 Publication Journal of Biological Rhythms Abbreviated Journal J Biol Rhythms  
  Volume 23 Issue 5 Pages 379-386  
  Keywords Human Health; Adult; Circadian Rhythm/*radiation effects; Female; Humans; *Light; Male; Melatonin/metabolism; Models, Biological; Neurosecretory Systems; Photons; Pineal Gland/metabolism; Retinal Ganglion Cells/*metabolism; Vision, Ocular  
  Abstract The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.  
  Address Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. george.brainard@jefferson.edu  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 0748-7304 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:18838601 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 724  
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Author Foster, R.G.; Hankins, M.W. url  doi
openurl 
  Title Circadian vision Type Journal Article
  Year (down) 2007 Publication Current Biology : CB Abbreviated Journal Curr Biol  
  Volume 17 Issue 17 Pages R746-51  
  Keywords Human Health; Animals; Circadian Rhythm/*physiology; Mice; Photoreceptor Cells, Vertebrate/*physiology; Rats; Rod Opsins/physiology; Vision, Ocular/*physiology  
  Abstract  
  Address Department of Ophthalmology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. russell.foster@eye.ox.ac.uk  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0960-9822 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:17803920 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 751  
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Author Cajochen, C.; Munch, M.; Kobialka, S.; Krauchi, K.; Steiner, R.; Oelhafen, P.; Orgul, S.; Wirz-Justice, A. url  doi
openurl 
  Title High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light Type Journal Article
  Year (down) 2005 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab  
  Volume 90 Issue 3 Pages 1311-1316  
  Keywords Human Health; Adult; Body Temperature Regulation/physiology/*radiation effects; Circadian Rhythm/physiology/radiation effects; Color; Heart Rate/physiology/*radiation effects; Humans; *Light; Male; Melatonin/*metabolism; Retinal Cone Photoreceptor Cells/physiology; Sleep Stages/physiology/radiation effects; Wakefulness/physiology/*radiation effects  
  Abstract Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.  
  Address Centre for Chronobiology, Psychiatric University Clinic, Wilhelm Kleinstr. 27, CH-4025 Basel, Switzerland. christian.cajochen@pukbasel.ch  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0021-972X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:15585546 Approved no  
  Call Number LoNNe @ kagoburian @ Serial 728  
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