Publications

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
[sleeping sickness: major disorders of circadian rhythm].	at the meningoencephalitis stage, human african trypanosomiasis (hat), sleeping sickness, causes dysregulation of the circadian rhythm of the sleep/wake cycle, rather than hypersomnia. in bedridden patients, total sleep time does not exceed 9 hours. the change in the 24-hour distribution of sleep and wakefulness is proportional to severity of clinical symptoms and laboratory abnormalities. the internal structure of sleep is also altered. all patients present sleep onset rapid eye movement period ...	2001	11803823
rhythmic hippocampal slow oscillation characterizes rem sleep in humans.	hippocampal rhythmic slow activity (rsa) is a well-known electrophysiological feature of exploratory behavior, spatial cognition, and rapid eye movement (rem) sleep in several mammalian species. recently, rsa in humans during spatial navigation was reported, but systematic data regarding human rem sleep are lacking. using mesio-temporal corticography with foramen ovale electrodes in epileptic patients, we report the presence of a 1.5-3-hz synchronous rhythmic hippocampal oscillation seemingly sp ...	2001	11811669
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
sleep disturbances after acute exposure to alcohol in mothers' milk.	the results of previous research in our laboratory revealed that breast-fed infants experience significantly less active sleep after exposure to alcohol in their mothers' milk than do breast-fed infants not exposed to alcohol. the present study tested the hypothesis that infants would compensate for such reductions if their mothers then refrained from drinking alcohol. to this end, 23 breast-fed infants from 3 to 5 months of age and their mothers were tested on 2 days separated by 1 week. a smal ...	2001	11839458
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
genetic technologies and courts of law.	human genetic testing, and its next logical technological plateau, gene therapy, are largely unregulated in the united states and much of the world. since the basic science and some of the technological know-how related to such tests and therapeutic regimes cross national boundaries, the disputes that follow in the wake of popular response to such technological advances could arise in virtually any court of the world. for much of the post-industrial world, this pits the unfettered processes of m ...	2000	11881639
studies on weightlessness in a primate in the biosatellite 3 experiment.	in june 1969 a male macaca nemestrina (pigtail macaque) was flown in earth orbit for 8.8 days in nasa biosatellite 3. the experiment examined in detail central nervous and cardiovascular functions, and included pre- and post-flight whole body metabolic assessment, in-flight urine analysis, and pre-and post-flight bone density measurements. although the sleep/wake cycle was 24 hr, a phase angle lag of 2 hr from the imposed night/day mode occurred. a definite desynchronosis occurred, with rhythms ...	1972	11898844
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
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
gulf money in kerala: coping with the problems of plenty.	the recent phenomenon of emigration from kerala to the gulf countries and the increasing inflow of remittances is having a tremendous impact on kerala's economy. the state planning board reports that the remittances from the gulf to this tiny state are rs. 400 crones/year. an annual inflow of this amount cannot help influence the fortunes of the population. although emigration from kerala is not new, the current outflow reached massive proportions only in the wake of the intensive constructio ...	1979	12265616
[how to promote birth planning in the wake of transfer of agricultural production responsibility to the work crew].	mianzhu county is among sichuan province's more successful counties in family planning. following marx's theory of the 2-fold character of production, mianzhu county in 1980 simultaneously transferred both agricultural production and family planning work to the work crew by implementing "double transfer of responsiblity," thereby mobilizing cadres and people to understand both time material production and human reproduction, i.e., "grains, money and people." last year when the agricultural pro ...	1981	12266520
careful monitoring of human rights needed -- dr. wiwat rojanapithayakorn.	in his talk, joint un program on hiv/aids team leader dr. wiwat rojanapithayakorn made a plea for the careful monitoring of human rights with respect to the hiv/aids epidemic. since the start of the hiv/aids pandemic, a total of 47 million people have been infected with hiv, 14 million have died of aids, with 33 million afflicted with the virus by the end of 1998. in the wake of this global crisis comes the widespread abuse of human rights and fundamental freedoms worldwide. many hiv/aids pat ...	1999	12295690
samoa: the realities of living with hiv in samoa.	how does a pacific country deal with someone who is hiv positive? what support can be expected from society and family if one is infected by hiv? how does the rhetoric of being a family-oriented and caring society fit with the realities of what happens to hiv positive people? this presentation talks about the experience of an hiv positive woman. peati maiava is from samoa. she was married in june 1992 and subsequently had two sons. her youngest son, fiti, died after much suffering of an und ...	2000	12295867
condom promotion and use: family planning versus hiv protection.	condoms have been used since the 16th century as a prophylactic agent against sexually transmitted diseases. with regards to family planning, condoms are used for spacing and prevention of pregnancy. however, after the invention of more reliable contraceptives, condoms lost their popularity as a contraceptive agent, only to regain it in the wake of the aids epidemic. the main concern in using condoms has always been the high failure rate, which tends to be a complicated issue given that it's ...	1989	12316117
health care and human rights.	on april 6, 1995, in new delhi, india, demonstrators with the group aids bhedbhav virodhi andolan (abva) protested against the death of an aids patient in calcutta due to medical negligence. they observed two minutes of silence in the memory of dipak biswas and carried signs stating fight aids not aids patients, aids patients have human rights, and wake up, national human rights commission. the demonstrators also submitted a memorandum to the chairman of the national human rights commission and ...	1995	12319587
the use and abuse of female domestic workers from sri lanka in lebanon.	women who migrate from sri lanka to become domestic workers in lebanon face gender, class, and race discrimination that often results in abuse, yet the predicament of these women is largely ignored by local and international humanitarian and human rights agencies. public consciousness about the plight of asian domestic workers in the persian gulf region was raised in 1990 when domestic workers were repatriated in the wake of the gulf war. in lebanon, nearly half of the work permits granted to ...	1998	12321536
bringing its results and benefits. mozambique. the hague forum.	in the wake of the 1994 international conference on population and development (icpd), and given the country's high rate of population growth, mozambique developed a national population policy to facilitate the implementation of the icpd program of action at the national level, and to contribute to a smoother economic growth and better human development in the country. a fresh approach was used to create this population policy, although introducing a reproductive health perspective was a major ...	1999	12322185
female predominance of immigration to the united states since 1930: a first look.	immigration patterns in the us in the last 50 years have defied the conventional wisdom that most international migrants are young, working-age males. since 1930 more than 1/2 of all immgrants to the us have been women, and 2/3 have been women or children. data show that the persistently large number of marriages of foreign-born or native-born us residents to alien women, coupled with increasing government regulation of immigration and a strong policy bias against the seperation of spouces and ...	1984	12340340
china responds to the conference goals. responses to icpd.	china implemented a rural family planning program during the 1990s with the goal of helping families with fewer children to improve their standard of living. economic development and the development of a social security system has since improved living standards and reduced the need for large families. in the wake of the 1994 international conference on population and development (icpd) and its program of action committing the international community to quantitative goals in education, the red ...	1995	12346289
newsmaker interview: geraldine ferraro. striving for equality.	geraldine ferraro is a long-standing advocate of women's rights who currently serves as the us ambassador to the un's human rights commission. she was elected to the us congress in 1978, after which she served three terms as a representative from the state of new york. ms. ferraro led efforts to pass the equal rights amendment, sponsored the women's economic equity act, and ran on the democratic national ticket in 1984 as the first woman vice-presidential candidate. this paper presents the te ...	1995	12346510
sustainable development.	many attempts have been made over the last decade to define sustainable development (sd). however, it is much easier to describe one's expectations of sd. the discussion over sd grew in the wake of the brundlandt commission report, our common future (ocf), which describes sd as a process of change in which resources, the direction of investment, orientation of technological development, and institutional change all enhance the potential to meet human needs today and in the future. the ocf str ...	1996	12347747
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
narcolepsy: genetic predisposition and neuropharmacological mechanisms. review article.	narcolepsy is a disabling sleep disorder characterized by excessive daytime somnolence (eds), cataplexy and rem sleep-related abnormalities. it is a frequently-occurring but under-diagnosed condition that affects 0.02 to 0.18% of the general population in various countries. although most cases occur sporadically, familial clustering may be observed; the risk of a first-degree relative of a narcoleptic developing narcolepsy is 10-40 times higher than in the general population. the disorder is tig ...	2000	12531161
actigraphy in human psychopharmacology: a review.	over the last 25 years wrist actigraphy has predominantly been used in sleep research and chronobiology where the technique has proved useful in the measurement of sleep and the characterisation of the sleep/wake cycle. whilst there are a large number of studies published that have used actigraphy, there have only been relatively few studies that have shown that the technique is capable of measuring drug-induced changes in nocturnal and/or diurnal behaviour. thus the use of actigraphy to measure ...	2003	12532314
clinical pharmacokinetic profile of modafinil.	modafinil is a unique wake-promoting agent for oral administration. its pharmacological properties are distinct from those of other cns agents, and it selectively targets neuronal pathways in the sleep/wake centres of the brain. after single or multiple oral doses, modafinil is readily absorbed, reaching maximum plasma concentrations at 2-4 hours after administration and pharmacokinetic steady state within 2-4 days. its pharmacokinetics are dose-independent between 200 and 600 mg/day. the elimin ...	2003	12537513
distinctive effects of modafinil and d-amphetamine on the homeostatic and circadian modulation of the human waking eeg.	modafinil is a wake-promoting agent that affects hypothalamic structures involved in the homeostatic and circadian regulation of vigilance. administered during sleep deprivation, it reduces the need for prolonged recovery sleep and decreases the rebound in eeg slow-wave activity. these diachronic effects suggest an action of modafinil on a homeostatic sleep regulatory process.	2003	12552359
life between clocks: daily temporal patterns of human chronotypes.	human behavior shows large interindividual variation in temporal organization. extreme "larks" wake up when extreme "owls" fall asleep. these chronotypes are attributed to differences in the circadian clock, and in animals, the genetic basis of similar phenotypic differences is well established. to better understand the genetic basis of temporal organization in humans, the authors developed a questionnaire to document individual sleep times, self-reported light exposure, and self-assessed chrono ...	2003	12568247
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
['proteomics': the mapping of all human proteins].	the genomes of many organisms, including humans, are now largely known. in the wake of this there is a need to identify and measure all proteins that are encoded by the genome (proteomics). this need leads to turbulent developments in the area of analytical techniques, such as two-dimensional electrophoresis, mass spectrometry, and protein chips. the rapidity of advancements justifies the expectation that in the next 5-10 years it will indeed become possible to determine the proteome of an organ ...	2003	12577768
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
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
optimization of light and melatonin to phase-shift human circadian rhythms.	both light and melatonin, appropriately timed, have been shown to phase-shift human circadian rhythms. in addition, both light and melatonin have acute physiological and behavioural effects. depending on the dose, melatonin can reduce core body temperature and induce sleepiness. conversely, light at night increases body temperature and enhances alertness and performance. the acute and phase-shifting effects of light and melatonin have justified their investigation and use in the treatment of cir ...	2003	12622847
parvovirus b19 and autoimmune diseases.	parvovirus b19 (b19) causes many clinical disorders, of which the most common are erythema infectiosum, aplastic crisis complicating chronic hemolytic anemia, and hydrops fetalis. in young adults, the skin eruption caused by b19 is accompanied with polyarthritis and polyarthralgia in 60% of the cases. the joint abnormalities predominate in the hands and feet and usually resolve within a week (range 2-21 d). serological tests show igm antibodies against b19, confirming the diagnosis of recent inf ...	2003	12639611
circadian and homeostatic regulation of hypocretin in a primate model: implications for the consolidation of wakefulness.	in humans, consolidation of wakefulness into a single episode can be modeled as the interaction of two processes, a homeostatic "hour-glass" wake signal that declines throughout the daytime and a circadian wake-promoting signal that peaks in the evening. hypocretins, novel hypothalamic neuropeptides that are dysfunctional in the sleep disorder narcolepsy, may be involved in the expression of the circadian wake-promoting signal. hypocretins (orexins) are wake-promoting peptides, but their role in ...	2003	12716965
phase advancing human circadian rhythms with short wavelength light.	the photoreceptor(s) responsible for photoresetting of the human circadian system have not been identified. the aim of the present study was to assess the ability of short wavelength light to alter the timing of circadian rhythms. eleven male subjects were studied in 15 4-day trials with a single 4 h light pulse administered on day 3, immediately after habitual wake time. the magnitude of the phase shifts in the melatonin acrophase and offset were similar after white (4300 microw/cm(2)) and shor ...	2003	12727312
the berger lecture. chronobiology of sleep/wake and of sleepiness/alertness states in normal and sleep disordered human subjects.		2000	12740972
practice parameters for the role of actigraphy in the study of sleep and circadian rhythms: an update for 2002.	actigraphy is a method used to study sleep-wake patterns and circadian rhythms by assessing movement, most commonly of the wrist. these evidence-based practice parameters are an update to the practice parameters for the use of actigraphy in the clinical assessment of sleep disorders, published in 1995. these practice parameters were developed by the standards of practice committee and reviewed and approved by the board of directors of the american academy of sleep medicine. recommendations are b ...	2003	12749556
protecting human research subjects.	in early november, little more than a year after 18-year-old jesse gelsinger died in a gene-transfer trial at the university of pennsylvania, his family reached an unspecified settlement with the research team and institutions involved in the experiment. although the settlement with the university brought closure to the lawsuit, gelsinger's death raised lingering concerns about the risks of clinical trials involving human subjects. government investigations and hearings in the wake of the traged ...	2001	12751493
a subpopulation of rats show social and sleep-waking changes typical of chronic neuropathic pain following peripheral nerve injury.	neuropathic conditions for which treatment is sought, the so-called chronic pain syndrome, are characterized usually by complex behavioural disturbances as well as pain. in this study we evaluated whether social behavioural and sleep disruptions occurred after nerve injury. before and after chronic constriction of the sciatic nerve, resident-intruder and sleep-wake cycles, as well as mechanical and thermal allodynia/hyperalgesia, were quantified. sciatic nerve injury in all animals reduced withd ...	2003	12752790
theta oscillation in the anterior cingulate and beta-1 oscillation in the medial temporal cortices: a human case report.	in previous studies we observed gamma (30-150 hz) and beta-1 (10-20 hz) oscillations in the medial temporal lobe (mtl) using subdural electrodes. the beta-1 was present during wake and rem sleep while gamma was present in all states. recently we studied a patient (35 years m) with electrodes attached to the anterior cingulate cortex (acc). this structure showed regular theta (5-6 hz) oscillations. in the first recording, electrodes were attached to the mtl, that demonstrated the beta-1 and gamma ...	2003	12763350
simian virus 5 is a poor inducer of chemokine secretion from human lung epithelial cells: identification of viral mutants that activate interleukin-8 secretion by distinct mechanisms.	we have compared chemokine secretion from human lung a549 cells infected with simian virus 5 (sv5) with other members of the rubulavirus genus of paramyxoviruses. high levels of the chemokines interleukin-8 (il-8) and macrophage chemoattractant protein-1 (mcp-1) were secreted from a549 cells infected with human parainfluenza virus type 2 (hpiv-2) but not from cells infected with wild-type (wt) sv5. the lack of il-8 secretion from sv5-infected cells was not due to a global block in all signal tra ...	2003	12768033
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
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