Publications

neural basis and biological function of masking by light in mammals: suppression of melatonin and locomotor activity.	light influences mammalian circadian rhythms in two different ways: (1) it entrains endogenous oscillators (clocks), which regulate physiology and behavior; and (2) it affects directly and often immediately physiology and behavior (these effects are also referred to as masking). masking effects of light on pineal melatonin, locomotor activity, and the sleep-wake cycle in mammals and man are reviewed. they seem to represent a universal response in this group. the review reveals that the mechanism ...	2001	11763983
retinal circadian rhythms in humans.	circadian rhythms in the retina may reflect intrinsic rhythms in the eye. previous reports on circadian variability in electrophysiological human retinal measures have been scanty, and the results have been somewhat inconsistent. we studied the circadian variation of the electrooculography (eog), electroretinography (erg), and visual threshold (vth) in subjects undergoing a 36h testing period. we used an ultrashort sleep-wake cycle to balance effects of sleep and light-dark across circadian cycl ...	2001	11777083
studies on functional roles of the histaminergic neuron system by using pharmacological agents, knockout mice and positron emission tomography.	since one of us, takehiko watanabe (tw), elucidated the location and distribution of the histaminergic neuron system in the brain with antibody raised against l-histidine decarboxylase (a histamine-forming enzyme, hdc) as a marker in 1984 and came to tohoku university school of medicine in sendai, we have been collaborating on the functions of this neuron system by using pharmacological agents, knockout mice of the histamine-related genes, and, in some cases, positron emission tomography (pet). ...	2001	11908822
sleep and sleep-wake cycle in an 81-year-old patient with de novo ultra-rapid cycling bipolar disorder.	this is a case report of an 81-year-old man who developed de novo bipolar disorder with ultrarapid cycling at the age of 80. mood was self-rated daily over a period of ten weeks; in addition, polysomnographic and motor activity recordings were performed during a drug-free baseline period. both depressive and hypomanic episodes had an average duration of about 30 hours; the affective cycle was thus independent from the sleep-wake cycle. when mood shifts occurred during nighttime, sleep was differ ...	2001	11315515
behavioural-genetic perspectives on personality function.	in the wake of the recent announcements that the human genome has been mapped, efforts to identify the genetic loci underlying personality function will grow and intensify. much research has already been done in this area, but it has for the most part been limited to classical biometrical approaches designed to determine if personality has a heritable basis. these so-called "heritability" studies estimate how much of the individual differences in personality are attributable to genetic differenc ...	2001	11320677
defining the states of consciousness.	consciousness remains an elusive concept due to the difficulty to define what has been regarded for many years as a subjective experience, therefore irrelevant for scientific study. recent development in this field of research has allowed to provide some new insight to a possible way to define consciousness. going through the extensive literature in this domain, several perspectives are proposed to define this concept. (1) consciousness and attention may not reflect the same process. (2) conscio ...	2001	11323082
on-line detection of sleep-wake states and application to produce intermittent hypoxia only in sleep in rats.	sleep-disordered breathing is associated with adverse clinical consequences such as daytime sleepiness and hypertension. the mechanisms behind these associations have been studied in animal models, especially rats, but intermittent stimuli such as hypoxia have been applied without reference to sleep-wake states. to determine mechanisms underlying the adverse physiological consequences of stimuli associated with sleep-disordered breathing requires criteria for detection of sleep-wake states on-li ...	2001	11356775
decreased nocturnal levels of prolactin and growth hormone in women with fibromyalgia.	fibromyalgia (fm) is a complex syndrome, primarily of women, characterized by chronic pain, fatigue, and sleep disturbance. altered function of the somatotropic axis has been documented in patients with fm, but little is known about nocturnal levels of prl. as part of a laboratory study of sleep patterns in fm, we measured the serum concentrations of gh and prl hourly from 2000--0700 h in a sample of 25 women with fm (mean, 46.9 +/- 7.6 yr) and in 21 control women (mean, 42.6 +/- 8.1 yr). the me ...	2001	11297602
low-amplitude propagated contractile waves: a relevant propulsive mechanism of human colon.	human colonic motility is still poorly understood, especially as far as concerns its propulsive function. available data refer almost exclusively to the forceful propulsive activity, which is recognized as high-amplitude propagated contractions, the manometric equivalent of mass movements. by contrast, information on less vigorous propulsive contractions is still lacking.	2001	11303973
association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome.	recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (dsps) and non-24-h sleep-wake syndrome (n-24). we analyzed the human period3 (hper3) gene, one of the human homologs of the drosophila clock-gene period (per), as a possible candidate for rhythm disorder susceptibility. all of the coding exons in the hper3 gene were screened for polymorphisms by a pcr-based strategy using genomic dna samples fro ...	2001	11306557
the suprachiasmatic nucleus projects to posterior hypothalamic arousal systems.	the suprachiasmatic nucleus (scn) temporally organizes behavior in part by sustaining arousal during the wake period of the sleep/wake cycle to consolidate adaptive waking behavior. in this study, we demonstrate direct projections from the scn, in both the rat and the human brains, to perikarya and proximal dendrites of two groups of posterior hypothalamic neurons with axonal projections that suggest they are important in the regulation of arousal, one producing hypocretins (hct) and the other m ...	2001	11209963
charcot-marie-tooth disease and sleep apnoea syndrome: a family study.	charcot-marie-tooth (cmt) disease is a genetically heterogeneous group of hereditary motor and sensory polyneuropathies in which sleep apnoea has rarely been reported and no causal relation shown. we looked for an association between the most common subtype of cmt disease (cmt1a) and sleep apnoea syndrome.	2001	11214130
evidence from the waking electroencephalogram that short sleepers live under higher homeostatic sleep pressure than long sleepers.	we used the waking electroencephalogram to study the homeostatic sleep regulatory process in human short sleepers and long sleepers. after sleeping according to their habitual schedule, nine short sleepers (sleep duration < 6 h) and eight long sleepers (> 9 h) were recorded half-hourly during approximately 40 h of wakefulness in a constant routine protocol. within the frequency range of 0.25-20.0 hz, spectral power density in the 5.25-9.0 and 17.25-18.0 hz ranges was higher in short sleepers tha ...	2001	11226688
human melatonin regulation is not mediated by the three cone photopic visual system.	the aim of this study was to test if the three cone photopic visual system is the primary ocular photoreceptor input for human circadian regulation by determining the effects of different wavelengths on light-induced melatonin suppression. healthy subjects with stable sleeping patterns (wake-up time 7:30 am +/- 12 min) and normal color vision were exposed at night to full-field 505 nm or 555 nm monochromatic stimuli or darkness for 90 min. plasma collected before and after exposures was quantifi ...	2001	11232036
prenatal nicotine alters vigilance states and achr gene expression in the neonatal rat: implications for sids.	maternal smoking is a major risk factor for sudden infant death syndrome (sids). the mechanisms by which cigarette smoke predisposes infants to sids are not known. we examined the effects of prenatal nicotine exposure on sleep/wake ontogenesis and central cholinergic receptor gene expression in the neonatal rat. prenatal nicotine exposure transiently increased sleep continuity and accelerated sleep/wake ontogeny in the neonatal rat. prenatal nicotine also upregulated nicotinic and muscarinic cho ...	2001	11247836
bovine spongiform encephalopathy and variant creutzfeldt-jakob disease: background, evolution, and current concerns.	the epidemic of bovine spongiform encephalopathy (bse) in the united kingdom, which began in 1986 and has affected nearly 200,000 cattle, is waning to a conclusion, but leaves in its wake an outbreak of human creutzfeldt-jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. although averaging only 10-15 cases a year since its first appearance in 1994, its future magnitude and geographic distribution (in countries that have imp ...	2001	11266289
evidence for a biological dawn and dusk in the human circadian timing system.	1. because individuals differ in the phase angle at which their circadian rhythms are entrained to external time cues, averaging group data relative to clock time sometimes obscures abrupt changes that are characteristic of waveforms of the rhythms in individuals. such changes may have important implications for the temporal organization of human circadian physiology. 2. to control for variance in phase angle of entrainment, we used dual internal reference points--onset and offset of the nocturn ...	2001	11559786
history, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells.	in 1876, von kupffer described liver sternzellen (star-shaped cells). the functions of these cells remained enigmatic for 75 years until ito observed lipid-containing perisinusoidal cells in human liver. in 1971, wake demonstrated that the sternzellen of von kupffer and the fat-storing cells described by ito were identical. wake also established that these cells were important sites of vitamin a storage. soon thereafter, kent and popper demonstrated that the stellate cells were intimately linked ...	2001	11586463
autoantibodies to pancreatic hsp60 precede the development of glucose intolerance in patients with cystic fibrosis.	persons expressing the genetic disease cystic fibrosis (cf) suffer from a high risk of developing impaired glucose tolerance and diabetes. the development of diabetes in cf has been attributed, in the past, to the destruction of pancreatic islets and their resident beta-cells secondary to the destruction of the surrounding tissue by mechanical clogging of the pancreatic exocrine ducts. however, the discovery that autoimmunity to the 60-kda heat shock protein (hsp60) may cause type i diabetes in ...	2001	11591125
bloodborne pathogens: updating sharps safety.	osha's new compliance directive was a wake-up call telling healthcare employers they must use safer technology and safer work practices.	2001	11602984
predictors of incidence and prevalence of green tobacco sickness among latino farmworkers in north carolina, usa.	the characteristics of some populations make epidemiological measurement extremely difficult. the objective of this study is to identify risk factors that explain variation among incidence densities and proportions of one occupational illness, green tobacco sickness, within one such special population, latino migrant and seasonal farmworkers in the united states.	2001	11604438
neuroimmunologic aspects of sleep and sleep loss.	the complex and intimate interactions between the sleep and immune systems have been the focus of study for several years. immune factors, particularly the interleukins, regulate sleep and in turn are altered by sleep and sleep deprivation. the sleep-wake cycle likewise regulates normal functioning of the immune system. although a large number of studies have focused on the relationship between the immune system and sleep, relatively few studies have examined the effects of sleep deprivation on ...	2001	11607924
complex sound processing during human rem sleep by recovering information from long-term memory as revealed by the mismatch negativity (mmn).	perceptual learning is thought to be the result of neural changes that take place over a period of several hours or days, allowing information to be transferred to long-term memory. evidence suggests that contents of long-term memory may improve attentive and pre-attentive sensory processing. therefore, it is plausible to hypothesize that learning-induced neural changes that develop during wakefulness could improve automatic information processing during human rem sleep. the mmn, an objective me ...	2001	11368962
mouse model for morningness/eveningness.	human morning/evening preferences has recently been reported to be associated with polymorphism of the 3' flanking region of the clock gene, which was the first identified mammalian circadian clock gene. we recorded body temperature, spontaneous activity, electroencephalogram and electromyogram for 48 h in mice with jcl:icr genetic background and homozygous for the clock mutation (cl/cl on jcl:icr). in both wild-type and cl/cl on jcl:icr, body temperature, activity, wake and sleep were completel ...	2001	11388430
predicting behavioral changes associated with age-related cognitive impairment in dogs.	to monitor the progression of age-related behavioral changes in dogs during a period of 6 to 18 months and to determine whether signs of dysfunction in any of 4 behavioral categories can be used to predict further impairment.	2001	11394832
human aging and melatonin. clinical relevance.	melatonin is a hormone produced mainly by the pineal gland and secreted primarily at night, when it reaches levels 10 times higher than those present in the daytime. the highest melatonin levels are found in children younger than 4 yr; thereafter melatonin levels begin to decline with age. as a chronobiotic, melatonin acts on sleep by phase-advancing or delaying the sleep--wake cycle so that sleep onset occurs earlier or later than usual. beneficial effects of melatonin have been observed in del ...	2001	11404053
phase-advance shifts of human circadian pacemaker are accelerated by daytime physical exercise.	effects of forced sleep-wake schedules with and without physical exercise were examined on the human circadian pacemaker under dim light conditions. subjects spent 15 days in an isolation facility separately without knowing the time of day and followed a forced sleep-wake schedule of a 23 h 40-min period for 12 cycles, and physical exercise was imposed twice per waking period for 2 h each with bicycle- or rowing-type ergometers. as a result, plasma melatonin rhythm was significantly phase advanc ...	2001	11404294
mastering the value chain. an interview with mark levin of millennium pharmaceuticals. interview by david champion.	as today's business leaders are all too aware, a new scientific or technological break-through can quickly transform an industry's competitive landscape. the upheaval is often traumatic for the companies involved, forcing them to rethink their strategies and redefine their boundaries. but an industry in flux also creates vast opportunities. to seize them, companies must see how the current upheavals will affect the future distribution of profits--and then reinvent themselves to capitalize on the ...	2001	11408971
drug discovery in the wake of genomics.		2001	11434347
familial advanced sleep phase syndrome.	the circadian rhythms of sleep propensity and melatonin secretion are regulated by a central circadian clock, the suprachiasmatic nucleus of the hypothalamus. the most common types of sleep disorders attributed to an alteration of the circadian clock system are the sleep/wake cycle phase disorders, such as delayed sleep phase syndrome and advanced sleep phase syndrome (asps). advanced sleep phase syndrome is characterized by the complaint of persistent early evening sleep onset and early morning ...	2001	11448298
non-rapid-eye-movement sleep propensity after sleep deprivation in human subjects.	the circadian modulation of occurrence of non-rapid-eye-movement sleep (nrem) was investigated in 37 volunteers under dim-light conditions after 24-h total sleep deprivation using a 26-h 10/20-min ultra-short sleep-wake schedule. the propensity of nrem showed rapid increase followed by gradual decrease during the subjective day and nocturnal bouts during the subjective night coinciding with melatonin production. the mean propensity of nrem during the subjective day was smaller than that during t ...	2002	11911980
human alpha oscillations in wakefulness, drowsiness period, and rem sleep: different electroencephalographic phenomena within the alpha band.	cortical oscillations in the range of alpha activity (8-13 hz) are one of the fundamental electrophysiological phenomena of the human electroencephalogram (eeg). evidence from quantitative eeg data has shown that their electrophysiological features, cortical generation mechanisms, and therefore, their functional correlates vary along the sleep-wake continuum. specifically, spectral microstructure and eeg coherence levels between anterior and posterior cortical regions permit to differentiate amo ...	2002	11915486
mutation screening of the human clock gene in circadian rhythm sleep disorders.	we tested whether the human clock (hclock) gene, one of the essential components of the circadian oscillator, is implicated in the vulnerability to delayed sleep phase syndrome (dsps) and non-24-hour sleep-wake syndrome (n-24). screening in the entire coding region of the hclock gene with pcr amplification revealed three polymorphisms, of which two predicted the amino acid substitutions r533q and h542r. the frequencies of the r533q and h542r alleles in patients with dsps or n-24 were very low an ...	2002	11927136
ceramic photocell implants could restore sight.	researchers are perfecting the use of ceramic photocells for retinal implantation. the work is being done at the space vacuum epitaxy center in houston, tx. the photocells are the results of experiments with oxide detectors conducted in space using the wake shield facility. artificial retinas are constructed of 100,000 microscopic ceramic detectors attached to a polymer film, which disintegrates after implantation. initially, four arrays will be implanted, totalling 400,000 detectors per eye. if ...	2002	11951916
ethics in international health research: a perspective from the developing world.	health research plays a pivotal role in addressing inequities in health and human development, but to achieve these objectives the research must be based on sound scientific and ethical principles. although it is accepted that ethics play a central role in health research in developing countries, much of the recent debate has focused on controversies surrounding internationally sponsored research and has taken place largely without adequate participation of the developing countries. the relation ...	2002	11953789
circadian rhythms from flies to human.	in this era of jet travel, our body 'remembers' the previous time zone, such that when we travel, our sleep wake pattern, mental alertness, eating habits and many other physiological processes temporarily suffer the consequences of time displacement until we adjust to the new time zone. although the existence of a circadian clock in humans had been postulated for decades, an understanding of the molecular mechanisms has required the full complement of research tools. to gain the initial insights ...	2002	12015613
[pathophysiology of rett syndrome from the standpoints of clinical characteristics and clinical neurophysiological findings].	the pathophysiology of rett syndrome (rtt) was discussed by reviewing the characteristic clinical features and neurophysiological studies. the electroencephalography (eeg), sensory evoked potentials (sep), sleep-wake rhythm (swr) study and polysomnographical (psg) study showed age dependent characteristics. the findings in eeg and sep studies suggested the specific subcortical and cortical involvements taking place during the development. psg suggested the early dysfunction of the brainstem and ...	2002	12030007
assessment of spontaneously occurring periodic limb movements in sleep in the rat.	periodic limb movements in sleep (plms) are often associated with the restless legs syndrome (rls). although the dopaminergic system seems to be involved, the pathophysiology of plms and rls is still obscure. the objective of this study is to explore whether a plms-like phenomenon can be observed in rodents in order to elucidate the underlying mechanisms.	2002	12039666
sleep, feeding, and neuropeptides: roles of orexins and orexin receptors.	recent studies using molecular genetics in mice and dogs, as well as histopathological analyses of human disease, have come to the same conclusion: the human sleep disorder narcolepsy is caused by failure of signaling mediated by orexin (hypocretin) neuropeptides. these and other findings strongly suggest that the orexin system plays a critical role in sleep/wake regulation. in addition, the orexin system may link energy homeostasis to the regulation of sleep/wake cycles.	2002	12049942
polysomnographic findings in five adult patients with pituitary insufficiency before and after cessation of human growth hormone replacement therapy.	we observed the new onset of severe obstructive sleep apnoea syndrome (osas) in an adult male patient during human growth hormone (hgh) replacement therapy. this prompted us to evaluate the potential influence of hgh substitution therapy on sleep in middle-aged men.	2002	12072052
orexins: from neuropeptides to energy homeostasis and sleep/wake regulation.	the neuropeptides orexin a and orexin b (also called hypocretin 1 and 2) were recently discovered by a "reverse pharmacology" approach as ligands for two previously orphan g protein coupled receptors: orexin receptors 1 and 2. neurons producing orexins are located exclusively in the lateral hypothalamic area but project broadly to various parts of the brain, and they have been implicated in the control of energy homeostasis and arousal maintenance. the orexin receptors are also broadly expressed ...	2002	12072908
greater daytime sleepiness in subcortical stroke relative to parkinson's disease and alzheimer's disease.	deficits in daytime alertness in the elderly may reflect, in part, deterioration of the critical neural systems modulating circadian control of sleep and wakefulness. in this study, 47 patients with subcortical stroke (n = 9), alzheimer's disease (n = 6), and parkinsonism (n = 32) underwent a 24-hour in-laboratory evaluation consisting of overnight polysomnography and next-day evaluation of daytime sleep tendency with the multiple sleep latency test. patients with stroke were significantly sleep ...	2002	12083594
sleep states differentiate single neuron activity recorded from human epileptic hippocampus, entorhinal cortex, and subiculum.	animal models of epilepsy have shown that synchronous burst firing is associated with epileptogenesis, yet the evidence from human studies linking neuronal synchrony and burst firing to epileptogenesis remains equivocal. sleep-wake states have been shown to differentially modulate the generation of epileptiform eeg spikes between brain regions of greater and lesser seizure-generating potential, providing information that helps to identify the primary epileptogenic region. using these state-depen ...	2002	12097521
theoretical and practical considerations in the application of whole body plethysmography to sleep research.	the sleep-wake state has a profound influence on many, perhaps most, aspects of normal physiology and is strongly implicated in the mediation (or remediation) of impaired health and performance. many sleep disorders stem from abnormal respiratory anatomy or sleep-induced changes in respiratory control, underscoring the need for research into the effects of the sleep-wake state on respiratory control processes. whole body plethysmography is being increasingly used to study respiration in freely b ...	2002	12111280
beta-cit spect demonstrates reduced availability of serotonin transporters in patients with fatal familial insomnia.	fatal familial insomnia (ffi) is a rare hereditary human prion disease with unique clinical features including progressive sleep impairment and autonomic dysfunction. the serotonergic system is considered to be involved in the regulation of the sleep-wake cycle. in this study we demonstrate a reduced availability of serotonin transporters of 57% and 73% respectively in a thalamus-hypothalamus region of two ffi patients examined with beta-cit spect as compared to age-expected control values.	2002	12111447
education in a genomic world.	if a transformation in medicine occurs in the wake of the human genome project, its likely focus will be prevention, a logical extension of the lessons of variation and individuality inherent in molecular genetics. the transformation of medicine will require a transformation in genetics education as well, focusing on the development of genetic literacy that allows patient and provider to collaborate as partners in health promotion and disease prevention. the components of genetic literacy includ ...	2002	12187440
the physiology and pharmacology of the orexins.	orexin-a and orexin-b are two peptides derived by proteolytic cleavage from a 130 amino acid precursor prepro-orexin, which recently were isolated from the rat hypothalamus. orexin-a is fully conserved across mammalian species, whilst rat and human orexin-b differ by 2 amino acids. these peptides bind to two g(q)-coupled receptors, termed ox(1) and ox(2). the receptors are 64% homologous and highly conserved across species. orexin-a is equipotent at ox(1) and ox(2), whilst orexin-b displays mode ...	2002	12191593
genetic variability in response to infection: malaria and after.	recent studies have shown that the relatively short period of exposure of human populations to malaria has left in its wake a wide range of genetic diversity. and there is growing evidence that other infectious agents have, or are, having the same effect. by integrating further studies of human populations with genetic analyses of susceptibility to murine malaria it should now be possible to determine some of the mechanisms involved in the variation of susceptibility to infectious disease, infor ...	2002	12209359
homeostatic control of slow-wave and spindle frequency activity during human sleep: effect of differential sleep pressure and brain topography.	the impact of a 40 h sleep deprivation versus a 40 h multiple nap paradigm on topographic and temporal aspects of electroencephalographic (eeg) activity during the subsequent recovery sleep was investigated in 10 young volunteers in a controlled 'constant posture' protocol. the accumulation of sleep pressure with extended wakefulness could be significantly attenuated by intermittent naps. the differential sleep pressure conditions induced frequency- and topographic-specific changes in the eeg sl ...	2002	12217973
sleep-waking discharge patterns of neurons recorded in the rat perifornical lateral hypothalamic area.	the perifornical lateral hypothalamic area (pf-lha) has been implicated in the control of several waking behaviours, including feeding, motor activity and arousal. several cell types are located in the pf-lha, including projection neurons that contain the hypocretin peptides (also known as orexins). recent findings suggest that hypocretin neurons are involved in sleep-wake regulation. loss of hypocretin neurons in the human disorder narcolepsy is associated with excessive somnolence, cataplexy a ...	2002	11790824
integration of human sleep-wake regulation and circadian rhythmicity.	the human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. the sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. it is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of t ...	2002	11796701
molecular genetic studies on sleep-wake regulation, with special emphasis on the prostaglandin d(2) system.	to elucidate the exact role of the pgd(2) system in sleep-wake regulation in vivo, the sleep behavior of knockout mice, generated in the author's and other laboratories, was examined for lipocalin-type pgd synthase (l-pgds), pgd receptor, adenosine a(2a) receptor, and histamine h(1) receptor; transgenic mice overexpressing the human l-pgds gene, generated in the author's laboratory, were also examined. the circadian profiles of sleep patterns of wild-type and the genetically manipulated mice wer ...	2002	11796702
diurnal variation of human corneal curvature in young adults.	to elucidate the diurnal variation of human corneal curvature with regard to gender and menstrual cycle.	2002	11828909
getting through to circadian oscillators: why use constant routines?	overt 24-h rhythmicity is composed of both exogenous and endogenous components, reflecting the product of multiple (periodic) feedback loops with a core pacemaker at their center. researchers attempting to reveal the endogenous circadian (near 24-h) component of rhythms commonly conduct their experiments under constant environmental conditions. however, even under constant environmental conditions, rhythmic changes in behavior, such as food intake or the sleep-wake cycle, can contribute to obser ...	2002	11837947
age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in pdapp mice.	recent studies demonstrated that mice overexpressing the human mutant beta-amyloid precursor protein (hbetaapp; pdapp mice) show age-independent and age-related deficits in spatial learning. we used behavioral and electrophysiological techniques to determine in young and aged pdapp mice whether deficits in spatial learning also involve alterations in sleep-wake states, thermoregulation and motor activity. consistent with earlier studies, young pdapp mice exhibited selective age-independent defic ...	2002	11844479
effects of nocturnal bright light on saliva melatonin, core body temperature and sleep propensity rhythms in human subjects.	nine healthy male volunteers (mean age of 24) participated in two experimental sessions of random crossover design: a bright light (5000 lux for 5 h from 00:00 to 05:00 h) session and a dim light (10 lux for 5 h from 00:00 to 05:00 h) session. subsequently participants entered an ultra-short sleep-wake schedule for 26 h, in which a sleep-wake cycle consisting of 10-min sleep eeg recording on a bed and 20-min resting awake on a semi-upright chair were repeated. saliva melatonin level and core bod ...	2002	11849730
actin' up (and down).	the côte d'azure provided a stunning backdrop for a recent conference* on the role of microfilament function and regulation in cell polarity. although sadly missing several north american participants in the wake of events in washington and new york, the largely european audience was nevertheless treated to fascinating insights into the many roles of actin polymerization and other processes involved in the establishment and maintenance of cell polarity. (*joint cnrs/jacques monod/embo conference ...	2002	11853994
sleep/wake cycles in the dark: sleep recorded by polysomnography in 26 totally blind subjects compared to controls.	to evaluate subjective sleep difficulties and nocturnal sleep with polysomnography in 26 completely blind subjects, living in normal social environments and to compare the findings with those of matched controls.	2002	12350437
direct evidence that "speedlines" influence motion mechanisms.	determining the direction of visual motion poses a serious problem for any visual system, given the inherent ambiguities. geisler (1999) has suggested that motion streaks left in the wake of a moving target provide a rich source of potential information that could aid in resolving direction ambiguities. here we provide strong experimental evidence that the human visual system does in fact exploit motion streaks in direction discrimination. masks comprising oriented random noise impeded direction ...	2002	12351740
cellular localization of cyclooxygenase-1 and cyclooxygenase-2 in the normal mouse, rat, and human retina.	prostaglandins, synthesized by cyclooxygenase (cox), regulate diverse neurophysiological actions such as regulation of autonomic responses, transmission of pain, generation of fever, control of sleep-wake cycle, synaptic signaling, and cross-talk between neurons and glia in the central nervous system. although prostaglandins have been widely studied in the anterior segment tissues of the eye, relatively little is known about prostaglandins in the neural retina. by using immunohistochemistry, we ...	2002	12355421
a phase dynamics model of human circadian rhythms.	nonphotic entrainment of an overt sleep-wake rhythm and a circadian pacemaker-driving temperature/melatonin rhythm suggests existence of feedback mechanisms in the human circadian system. in this study, the authors constructed a phase dynamics model that consisted of two oscillators driving temperature/melatonin and sleep-wake rhythms, and an additional oscillator generating an overt sleep-wake rhythm. the feedback mechanism was implemented by modifying couplings between the constituent oscillat ...	2002	12375623
age-related changes in sleep-wake rhythm in dog.	to investigate a sleep-wake rhythm in aged dogs, a radio-telemetry monitoring was carried out for 24 h. electrodes and telemetry device were surgically implanted in four aged dogs (16-18 years old) and four young dogs (3-4 years old). electroencephalogram (eeg), electromyogram (emg) and electrocardiogram (ecg) were recorded simultaneously as parameters to determine vigilance states and an autonomic nervous function. wakefulness, slow wave sleep (sws) and paradoxical sleep (ps) were identified ac ...	2002	12385805
cardiovascular disease and the global tobacco epidemic: a wake-up call for cardiologists.	the global tobacco epidemic continues unabated with the recruitment of young people, including women, to join the ranks of smokers. even though cardiovascular diseases account for some of the major tobacco-related morbidity and mortality, cardiologists and their professional societies have lagged behind in the crusade against tobacco. a great opportunity exists for more involvement and leadership role by cardiologists, especially in countries where tobacco control efforts are not well establishe ...	2002	12419555
origin and functional role of the extracellular serotonin in the midbrain raphe nuclei.	there is considerable interest in the regulation of the extracellular compartment of the transmitter serotonin (5-hydroxytryptamine, 5-ht) in the midbrain raphe nuclei because it can control the activity of ascending serotonergic systems and the release of 5-ht in terminal areas of the forebrain. several intrinsic and extrinsic factors of 5-ht neurons that regulate 5-ht release in the dorsal (dr) and median (mnr) raphe nucleus are reviewed in this article. despite its high concentration in the e ...	2002	12423765
epigenomics: genome-wide study of methylation phenomena.	epigenetics is one of the key areas of future research that can elucidate how genomes work. it combines genetics and the environment to address complex biological systems such as the plasticity of our genome. while all nucleated human cells carry the same genome, they express different genes at different times. much of this is governed by epigenetic changes resulting in differential methylation of our genome--or different epigenomes. individual studies over the past decades have already establis ...	2002	12432963
molecular genetics of timing in intrinsic circadian rhythm sleep disorders.	recent advances in circadian biology are identifying key genes and the molecular clockworks they command. these biochemical systems provide new tools for evaluating clinically observed, intrinsic circadian rhythm sleep disorders. a striking example was last year's discovery of a point mutation in a human clock gene that produces a sleep phase syndrome. this finding suggested that other intrinsic sleep disorders may have genetic underpinnings, and that less debilitating variations in sleep/wake b ...	2002	12452482
secretin and sleep in children with autism.	the objectives of this pilot study were 1) to examine possible effects of secretin infusions on sleep-wake state organization in children with autism, and 2) to assess the feasibility of home recordings using time-lapse videosomnography in children with autism. participants were a subset of subjects from two double blind, placebo-control, multi-center clinical trials. one trial, the uc irvine study, assessed the effects of porcine secretin vs. saline infusions on children's behavior, language an ...	2002	12462350
the 3111 clock gene polymorphism is not associated with sleep and circadian rhythmicity in phenotypically characterized human subjects.	mutations in clock genes are associated with abnormal circadian parameters, including sleep. an association has been reported previously between a polymorphism (3111c), situated in the 3'-untranslated region (3'-utr) of the circadian gene clock and evening preference. in the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free-running circadian rhythms and characterized with regard to circadian period (tau) an ...	2002	12464098
roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine h1 receptors in human brain.	brain histamine is involved in a wide range of physiological functions such as regulation of the sleep-wake cycle, arousal, cognition, and memory mainly through interactions with histamine h1 receptors (h1rs). neurons producing histamine, histaminergic neurons, are exclusively located in the posterior hypothalamus and transmit histamine to almost all regions of the brain. histamine h1 antagonists, or antihistamines, often prescribed for treatment of allergic disorders, sometimes induce sleepines ...	2002	12467881
right- and left-brain hemisphere. rhythm in reaction time to light signals is task-load-dependent: age, gender, and handgrip strength rhythm comparisons.	in healthy mature subjects simple reaction time (srt) to a single light signal (an easy task) is associated with a prominent rhythm with tau = 24 h of dominant (dh) as well as nondominant (ndh) hand performance, while three-choice reaction time (crt), a complex task, is associated with tau = 24 h of the dh but tau < 24 h of the ndh. the aims of the study were to assess the influence of age and gender on the difference in tau of the ndh and dh, as it relates to the corresponding cortical hemisphe ...	2002	12511028
mood and the circadian system: investigation of a circadian component in positive affect.	the aim of this study was to test if the pattern of human mood variation across the day is consistent with the hypothesis that self-reports of positive affect (pa) have a circadian component, and self-reports of negative affect (na) do not. data were collected under two protocols: normal ambulatory conditions of activity and rest and during a 27 h constant routine (cr) procedure. mood data were collected every 3 h during the wake span of the ambulatory protocol and hourly during the 27 h cr. in ...	2002	12511032
unsupervised continuous sleep analysis.	one aim of the eu-funded project siesta was to develop a new way of describing the human sleep-wake continuum with high temporal resolution, and independent of subjective rules, to serve as an alternative to traditional sleep scoring. here, we report new findings obtained with a fully automatic, probabilistic sleep-analyzer using hidden markov models (hmms) based on data from a single electroencephalogram (eeg) channel. hmms allow the analysis of non-stationary time series by modeling both the p ...	2002	12575468
sleep and circadian schedule disorders.	the timing and synchronization of human circadian rhythms is important for health and well-being. some individuals, for reasons that remain unclear, display less resilience or flexibility in their ability to synchronize to the 24-hour world and are thus diagnosed with a circadian schedule disorder. the objective of this article is to briefly introduce concepts about human circadian timing and to review what is known about chronic, long-term circadian schedule disorders such as delayed sleep phas ...	2002	12587363
disorders of the circadian clock: etiology and possible therapeutic targets.	the mammalian circadian clock in the suprachiasmatic nuclei (scn) of the hypothalamus conveys 24-hr rhythmicity to sleep-wake cycles, temperature, locomotor activity and virtually all other behavioral and physiological processes. in order for these cycles to be adaptive, they must be synchronized, or entrained, to the 24-hr light/dark cycle produced by the rotation of the earth. the timing of circadian variables relative to the light/dark cycle, i.e., the phase angle of entrainment, is influence ...	2002	12769597
the subjective effects of chewing qat leaves in human volunteers.	chewing the leaves of the qat plant (catha edulis) for their pleasurable central stimulant effect is a habit that is widespread in yemen and certain areas of east africa. the use of the qat leaves is believed to cause a variety of gastrointestinal and genito-urinary symptoms as well as sleep disturbance. we studied the subjective effects of chewing qat leaves in human volunteers.	2002	17259764
developing circadian rhythmicity in infants.	circadian rhythms are endogenously generated rhythms with a period length of about 24-hrs. evidence gathered over the past decade indicates that the circadian timing system develops prenatally and the suprachiasmatic nuclei, the site of a circadian clock, are present by mid-gestation in human and non-human primates. recent evidence also shows that the circadian system of primate infants is responsive to light at very premature stages and that low intensity lighting can regulate the developing cl ...	2003	16437011
toward a detailed computational model for the mammalian circadian clock.	we present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the per, cry, bmal1, clock, and rev-erb alpha genes. in agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between per/cry/rev-erbalpha and bmal1 mrnas. sustained oscillations correspond to the rhythms autonomously generated by suprachiasmat ...	2003	12775757
involvement of hypocretins/orexins in sleep disorders and narcolepsy.	the orexins/hypocretins are novel peptide neurotransmitters first characterized in 1998. the cell bodies of the neurons releasing them are localized exclusively in the posterior and lateral hypothalamus although they send out projections which innervate the whole central nervous system. they have recently attracted a great deal of interest in the neuroscience and medical community due to the finding that a reduction of orexin/hypocretins levels occurs in most human cases of the sleep disorder na ...	2003	12792667
presumed consent for transplantation: a dead issue after alder hey?	in the wake of scandals about the unauthorised retention of organs following postmortem examination, the issue of valid consent (or the lack of it) has returned to the forefront. emphasis is put on obtaining explicit authorisation from the patient or family prior to any medical intervention, including those involving the dead. although the controversies in the uk arose from the retention of human material for education or research rather than therapy, concern has been expressed that public mistr ...	2003	12796433
the human spermatozoon--not waving but drowning.	the poor quality of the human ejaculate sets man apart from all other mammalian species. even in normal fertile men the ejaculate may contain up to 85% abnormal forms according to the world heath organization (1999). in the wake of this poor semen quality comes extremely poor fertility (hull et al, 1985) and the highest rates of aneuploidy, pregnancy loss and birth defects in viviparous vertebrates. thus, the poor quality of human spermatozoa is reflected in both their capacity for fertilization ...	2003	12817679
strategic alternative responses to risks of terrorism.	the terrorist acts of september 11, 2001 were a wake-up call for changing our traditional response to risks of terrorism. given that government and worldwide think-tank organizations maintain that risks of terrorism will continue for the indefinite future, the following questions deserve strategic answers. how long can we respond to terrorism with tactical measures only, sustain current curtailments of some of our freedoms, travel, and quality of life, and absorb losses in human life and propert ...	2003	12836837
two pedigrees of familial advanced sleep phase syndrome in japan.	to determine whether a known missense mutation (bp2106 a/g) in hper2 (a human homolog of the drosophila period gene) for familial advanced sleep phase syndrome in a caucasian family is involved in japanese familial advanced sleep phase syndrome pedigrees.	2003	12841366
interspecific evolution: microbial symbiosis, endosymbiosis and gene transfer.	microbial symbioses are interesting in their own right and also serve as exemplary models to help biologists to understand two important symbioses in the evolutionary past of eukaryotic cells: the origins of chloroplasts and mitochondria. most, if not all, microbial symbioses have a chemical basis: compounds produced by one partner are useful for the other. but symbioses can also entail the transfer of genes from one partner to the other, which in some cases cements two cells into a bipartite, c ...	2003	12871231
diurnal variation of cerebrospinal fluid hypocretin-1 (orexin-a) levels in control and depressed subjects.	hypocretins, excitatory neuropeptides at monoaminergic synapses, appear to regulate human sleep-wake cycles. undetectable cerebrospinal fluid hypocretin-1 levels are seen in narcolepsy, which is frequently associated with secondary depression. shortened rapid eye movement latency is observed in both narcolepsy and depression. cerebrospinal fluid hypocretin-1 levels have not been reported in mood disorders.	2003	12873798
[yawning].	yawning is a normal reflex triggered by arousal, drowsiness, boredom, hunger and emotional conditions and it is associated to several neurological diseases and drug abuse. its wide presence in the phylogenetic vertebrate scale and even in human fetuses as young as 12 weeks directed the search for the common anatomic and biochemical mechanisms involved. the demonstration that yawning is not connected with high co2 or low o2 blood levels left aside a prevalent metabolic hypothesis. its close relat ...	2003	12876910
neuroendocrine profiles in mood disorders.	the study of neuroendocrine abnormalities in major mental illness, such as the unipolar and bipolar affective syndromes, has been the focus of interest in the past few years. the neuroendocrine window into the brain has been considered as a fruitful and promising approach to the study of mental disorders, as suggested by studies of some neuroendocrine challenge tests in depression that demonstrated their potential use as biological markers. the modern approach to hormonal dynamics focuses on the ...	2003	12890312
developing circadian rhythmicity in infants.	circadian rhythms are endogenously generated rhythms with a period length of approximately 24 hours. evidence gathered during the past decade indicates that the circadian timing system develops prenatally and the suprachiasmatic nuclei, the site of a circadian clock, is present by midgestation in primates. recent evidence also shows that the circadian system of primate infants is responsive to light at very premature stages and that low-intensity lighting can regulate the developing clock. after ...	2003	12897290
the influence of subjective alertness and motivation on human performance independent of circadian and homeostatic regulation.	endogenous circadian rhythmicity and sleep-wake homeostasis are robust regulators of human alertness and performance, yet few studies have examined how these regulatory processes affect motivation. moreover, the influence of alertness and motivation on performance, independent of circadian phase and hours awake, has not been studied. healthy subjects, 12 males and 3 females, ages 20 to 41, participated in a 2-week 28-h forced desynchrony protocol to address these issues. subjects performed a bat ...	2003	12932085
human circadian melatonin rhythm phase delay during a fixed sleep-wake schedule interspersed with nights of sleep deprivation.	the human circadian pacemaker, with an intrinsic period between 23.9 and 24.5 hr, can be reset by low levels of light. biomathematical models of the human clock predict that light-dark cycles consisting of only approximately 3.5 lux during 16 hr of wakefulness and 0 lux during 8 hr of sleep should entrain approximately 45% of the population. however, under real-life conditions, sleep-wake schedules and the associated light-dark exposures are often irregular. it remains unclear whether the phase ...	2003	12932197
investigating the interaction between the homeostatic and circadian processes of sleep-wake regulation for the prediction of waking neurobehavioural performance.	the two-process model of sleep regulation has been applied successfully to describe, predict, and understand sleep-wake regulation in a variety of experimental protocols such as sleep deprivation and forced desynchrony. a non-linear interaction between the homeostatic and circadian processes was reported when the model was applied to describe alertness and performance data obtained during forced desynchrony. this non-linear interaction could also be due to intrinsic non-linearity in the metrics ...	2003	12941057
the human body may buffer small differences in meal size and timing during a 24-h wake period provided energy balance is maintained.	because approximately 20% of the work force in the industrialized world have irregular working hours, it is pertinent to study the consequences of eating at irregular, especially nighttime hours. we studied the postprandial responses during nocturnal fasting vs. eating throughout a 24-h wake period. seven healthy males were studied twice in a crossover design. after a 6-d diet adjustment period [high fat diet, 45 energy percent (en%) fat, 40 en% carbohydrates)] with sleep from 2300 to 0700 h, th ...	2003	12949360
melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones.	the pineal hormone melatonin is a popular treatment for sleep and circadian rhythm disruption. melatonin administered at optimal times of the day for treatment often results in a prolonged melatonin profile. in photoperiodic (day length-dependent) species, changes in melatonin profile duration influence the timing of seasonal rhythms. we investigated the effects of an artificially prolonged melatonin profile on endogenous melatonin and cortisol rhythms, wrist actigraphy, and reproductive hormone ...	2003	12970302
miniaturized analytical assays in biotechnology.	biotechnology today is a well-established paradigm in many areas of human endeavor, such as the pharmaceutical industry, agriculture, management of the environment and many others. meanwhile, biology is undergoing a spectacular transition: whereas systematic biology was replaced gradually by molecular biology, the latter is rapidly being transformed into a new systematic era in which entire genomes are being charted by ever more sophisticated analytical techniques. in the wake of this onslaught ...	2003	14499125
therapeutic strategies for alzheimer disease: focus on neuronal reactivation of metabolically impaired neurons.	based on several lines of evidence, it has been hypothesized that decreased neuronal metabolic rate may precede cognitive impairment, contributing to neuronal atrophy as well as reduced neuronal function in alzheimer disease (ad). additionally, studies have shown that stimulation of neurons through different mechanisms may protect those cells from the deleterious effects of aging and ad, a phenomenon we paraphrased as "use it or lose it." therefore, it is attractive to direct the development of ...	2003	14512817
chromatin assembly factor 1 is essential and couples chromatin assembly to dna replication in vivo.	de novo chromatin assembly maintains histone density on the daughter strands in the wake of the replication fork. the heterotrimer chromatin assembly factor 1 (caf-1) couples dna replication to histone deposition in vitro, but is not essential for yeast cell proliferation. depletion of caf-1 in human cell lines demonstrated that caf-1 was required for efficient progression through s-phase. cells lacking caf-1 accumulated in early and mid s-phase and replicated dna slowly. the checkpoint kinase c ...	2003	14519857
topical review: sleep bruxism and the role of peripheral sensory influences.	sleep bruxism (sb) is an unusual orofacial movement described as a parafunction in dentistry and as a parasomnia in sleep medicine. since several peripheral influences could be involved in sleep-wake regulation and the genesis of rhythmic jaw movements, the authors have reviewed the relevant literature to facilitate understanding of mechanisms possibly involved in sb genesis. various animal and human studies indicate that during either wakefulness or anesthesia, orofacial sensory inputs (e.g., f ...	2003	14520766
dissociable stages of human memory consolidation and reconsolidation.	historically, the term 'memory consolidation' refers to a process whereby a memory becomes increasingly resistant to interference from competing or disrupting factors with the continued passage of time. recent findings regarding the learning of skilled sensory and motor tasks ('procedural learning') have refined this definition, suggesting that consolidation can be more strictly determined by time spent in specific brain states such as wake, sleep or certain stages of sleep. there is also renewe ...	2003	14534587
automated sleep staging in rat with a standard spreadsheet.	a new method of automated sleep-wake staging in the rat is described. hippocampal electroencephalographic (hpc) and nuchal electromyographic signals were recorded by a digital polygraph. the hpc channel was filtered off-line to obtain the original plus theta and delta waves. statistics of each of these four channels were obtained every 5 s and exported to a standard spreadsheet. the automated staging consisted of five steps: (1) automatic detection of waking, nonrapid eye movement sleep and rapi ...	2003	14583408
sleep-wake states and their regulatory mechanisms throughout early human development.	the emergence of sleep states is one of the most significant aspects of development. descriptions of both neonatal and late fetal behavior and studies on the organization of sleep have shown that fetus and newborns exhibit spontaneously discrete and cyclic patterns of active sleep (as) and quiet sleep (qs). human fetuses and neonates sleep most of their life, and as is the prevailing state even during the first postnatal months. several hypotheses to explain central nervous system development co ...	2003	14597916
development under extreme conditions: forensic bioinformatics in the wake of the world trade center disaster.	the terrorist attacks of september 11, 2001 resulted in death and devastation in three locations, and extraordinary efforts have been exerted to identify the remains of all victims. as mass fatalities go, this one has been unusual at a policy level because the goal has been not merely to identify remains for every decedent, but to identify every bit of remains found so that even small pieces of tissue can be returned to families for burial. while the human impact at the pentagon and shanksville, ...	2003	12603064