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Biomedical subjects

S S Campbell

Publications and source records attributed to S S Campbell.

At least 19 recordsLinked to original sources
PubMed2004

Human keratin 8 mutations that disturb filament assembly observed in inflammatory bowel disease patients.

We have identified miss-sense mutations in keratin 8 in a subset of patients with inflammatory bowel disease (Crohn disease and ulcerative colitis). Inflammatory bowel diseases are a group of disorders that are polygenic in origin and involve intestinal epithelial breakdown. We investigated the possibility that these keratin mutations might contribute to the course of the disease by adversely affecting the keratin filament network that provides mechanical support to cells in epithelia. The mutations (Gly62 to Cys, Ile63 to Val and Lys464 to Asn) all lie outside the major mutation hotspots associated with severe disease in epidermal keratins, but using a combination of in vitro and cell culture assays we show that they all have detrimental effects on K8/K18 filament assembly in vitro and in cultured cells. The G62C mutation also gives rise to homodimer formation on oxidative stress to cultured intestinal epithelial cells, and homodimers are known to be polymerization incompetent. Impaired keratin assembly resulting from the K8 mutations found in some inflammatory bowel disease patients would be predicted to affect the maintenance and re-establishment of mechanical resilience in vivo, as required during keratin cytoskeleton remodeling in cell division and differentiation, which may lead to epithelial fragility in the gut. Simple epithelial keratins may thus be considered as candidates for genes contributing to a risk of inflammatory bowel disease.

Actin Cytoskeleton↗
PubMed2002

Ultrastructural aspects of the development of the hyaline layer and extracellular matrix lining the gastrointestinal tract in embryos and larvae of the starfish Pisaster ochraceus preserved by freeze substitution.

Embryos and larvae of the starfish Pisaster ochraceus are surrounded by a complex extracellular matrix (ECM) layer called the hyaline layer (HL). A similar but less well-organized ECM layer lines some regions of the larval gut. Examination of material preserved by freeze substitution shows that the HL consists of a coarse outer meshwork, a boundary layer, a supporting layer, which is divided into three sublayers, H1, H2, and H3, and an intervillus layer. The development of the HL has been studied in material preserved by freeze substitution. Development begins at fertilization when exocytosis of the cortical granules releases ECM into the perivitelline space and elevates the fertilization membrane. Shortly after, plaques of dense material with attached fibers are present on the outer surface of the egg plasmalemma. Following this, these plaques and fibers are associated with the tips of short microvilli, suggesting that they may induce microvillus formation. Next, the tips of some of the microvilli are joined by short regions of the H1 sublayer. Some of these H1 regions have short segments of boundary layer material associated with their outer surfaces while others are naked. Just prior to hatching, the H1 and boundary layers completely surround the embryo, separating the developing coarse meshwork and intervillus layers. Short segments of the H2 and H3 sublayers are also present. Posthatching, the microvilli and all HL layers increase in thickness and density, particularly the H2, boundary, and coarse outer meshwork layers. The results suggest a sequential organization of HL components from ECM that is secreted into the perivitelline space.

Animals↗
PubMed2001

Long-term time estimation is influenced by circadian phase.

The adaptive significance of a putative time sense in humans remains unclear as do the factors that underlie the capacity to gauge the passage of time. Here we show that the subjective assessment of relatively long durations varies systematically as a function of time of day. Specifically, the subjective clock ran relatively faster when the circadian oscillation of body temperature was on the rise and relatively slower on the declining portion of the temperature curve. The overall result was a rather labile clock that, on average, ran slow relative to physical time. The results provide a glimpse into an underexplored aspect of how humans use their endogenous clocks in the most fundamental way--to gauge the passage of time.

Adolescent↗
PubMed2001

Extraocular phototransduction and circadian timing systems in vertebrates.

It is widely accepted that, for organisms with eyes, the daily regulation of circadian rhythms is made possible by light transduction through those organs. Yet, it has been demonstrated repeatedly in recent years that ocular light receptors that mediate vision, at least in mammals, are not the same photoreceptors involved in circadian regulation. Moreover, it has been recognized for many years that circadian regulation can occur in organisms without eyes. In fact, extraocular circadian phototransduction (EOCP) appears to be a phylogenetic rule for the vast majority of species. EOCP has been reported in every nonmammalian species studied to date. In mammals, however, the story is very different. This paper presents findings from studies that have examined specifically the capacity for EOCP in vertebrate species. In addition, the literature addressing noncircadian aspects of extraocular phototransduction is briefly discussed. Finally, possible mechanisms underlying EOCP are discussed, as are some of the implications of the presence, or absence, of EOCP across phylogeny.

Amphibians↗
PubMed2001

Enhancement of REM sleep during extraocular light exposure in humans.

This study examined the effects on sleep of light administered to an extraocular site. A 3-h photic stimulus was applied to the popliteal region during sleep in 14 human subjects. Each subject also underwent a control stimulus condition during a separate laboratory session. The proportion of rapid eye movement (REM) sleep during the 3-h light administration session increased by an average of 31% relative to the control condition. The frequency but not the duration of REM episodes was altered during light exposure, thereby shortening the REM/non-REM (NREM) cycle length. No other sleep stages were significantly affected during light administration nor was sleep architecture altered after the light-exposure interval. These results confirm that extraocular light is transduced into a signal that is received and processed by the human central nervous system. In addition, they expand to a novel sensory modality previous findings that REM sleep can be enhanced by sensory stimulation.

Circadian Rhythm↗
PubMed2000

Age differences in the spontaneous termination of sleep.

The stage from which the spontaneous ending of sleep occurred was investigated in 138 sleep episodes obtained from 14 younger (19-28 years) and 11 older (60-82 years) individuals. The possible influences of circadian phase and quality of the preceding sleep period, as well as the impact of aging on characteristics of sleep termination were examined. Under experimental conditions in which subjects were isolated from time cues, and behavioral options to sleep were limited, no age-associated differences in the duration of sleep periods, or in the number or duration of REM episodes were observed. Despite similar percentages of NREM (stages 2-4) and REM sleep across age groups, younger subjects awakened preferentially from REM while older subjects did not. Of the sleep episodes obtained from older subjects, those with sleep efficiencies higher than the median were more likely to terminate from REM than those with lower sleep efficiencies. For all subjects, the REM episodes from which sleep termination occurred were truncated relative to those that did not end the sleep period. In addition, nonterminating REM episodes that were interrupted by a stage shift were most often interrupted by brief arousals to stage 0. Such arousals within nonterminating REM episodes occurred, on average, after a similar duration as the terminating point of sleep-ending REM episodes. The results from this study demonstrate that there are age-related differences in the sleep stage from which spontaneous awakenings occur, and that these differences may be due in part to the quality of the sleep period preceding termination. Findings regarding the characteristics of both terminating and nonterminating REM episodes are consistent with the notion that the neural and biochemical context of REM sleep may facilitate a smooth transition to wakefulness. It is speculated that age-associated changes in sleep continuity may render unnecessary the putative role of REM sleep in providing a 'gate' to wakefulness.

Adult↗
PubMed1999

EEG theta activity and pain insensitivity in self-injurious borderline patients.

The principal aim of this study was to investigate possible neurophysiological underpinnings of self-injurious behavior in women with borderline personality disorder (BPD). Pain report and EEG power spectrum density during a laboratory pain procedure, a 4-min 10 degrees C cold pressor test (CPT), were compared among four groups; female inpatients with BPD who do (BPD-P group, n = 22) and do not (BPD-NP group, n = 19) report pain during self-injury, female inpatients with major depression (n = 15), and normal women (n = 20). The BPD-NP group reported less pain intensity during the CPT compared to the other groups. Total absolute theta power was significantly higher in the BPD-NP group compared to the Depressed (P = 0.0074) and Normal (P = 0.0001) groups, with a trend toward being significantly higher compared to the BPD-P group (P = 0.0936). Dissociative Experience Scale scores were significantly higher in the BPD-NP group compared to the Depressed and Normal groups (maximum P = 0.0004), and significantly higher in the BPD-P group compared to the Normal group (P = 0.0016). Beck Depression Inventory and Sheehan Patient Rated Anxiety Scale scores were significantly lower in the Normal group compared to all patient groups. Theta activity was significantly correlated with pain rating (Pearson partial r = -0.43, P = 0.0001) and Dissociative Experiences Scale score (Pearson partial r = 0.32, P = 0.01).

Adolescent↗
PubMed1999

Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome.

The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or lying and also worsen at night. The current study was designed to determine if the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by an independent circadian factor. We recorded sleeping and waking PLMs and waking sensory symptoms in eight volunteers with RLS for 3 successive nights and days, starting with a polysomnographic recording of 2 nights, followed by a third night of sleep deprivation and the day after sleep deprivation. This study showed that both the PLMs and sensory symptoms were worst at night with a maximum for both between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of sleep deprivation. Circadian temperature curves were normal in all four patients with adequate data collection. The highest PLM counts occurred on the falling phase of the circadian temperature curve whereas the lowest PLM counts occurred on the rising phase of the curve. We conclude that the PLM and sensory symptoms in RLS are influenced by a circadian rhythm, and that the "worsening at night" criterion of the RLS Definition Criteria is, at least in part, distinct from the "worsening while lying or sitting" criterion.

Adult↗
PubMed1999

Etiology and treatment of intrinsic circadian rhythm sleep disorders.

Some individuals experience an acute or chronic sleep disturbance, associated with a misalignment between the timing of their sleep and the sleep-wake cycle that is desired, or considered normal by society. It is estimated that 5-10% of insomniacs seeking treatment have this type of disorder, collectively called circadian rhythm sleep disorders. This paper reviews circadian rhythm sleep disorders of the intrinsic type, which include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, and irregular sleep-wake pattern. For each disorder, we present data addressing its pathophysiology and potential treatments, including the use of behavioral measures and chronotherapy, bright light treatment and pharmacological treatments such as melatonin. We conclude by addressing some of the limitations and drawbacks of the various treatments.

Journal Article↗
PubMed1999

Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans.

Biological circadian clocks oscillate with an approximately 24-hour period, are ubiquitous, and presumably confer a selective advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock. Autosomal semi-dominant mutations in rodents with fast or slow biological clocks (that is, short or long endogenous period lengths; tau) are associated with phase-advanced or delayed sleep-wake rhythms, respectively. These models predict the existence of familial human circadian rhythm variants but none of the human circadian rhythm disorders are known to have a familial tendency. Although a slight 'morning lark' tendency is common, individuals with a large and disabling sleep phase-advance are rare. This disorder, advanced sleep-phase syndrome, is characterized by very early sleep onset and offset; only two cases are reported in young adults. Here we describe three kindreds with a profound phase advance of the sleep-wake, melatonin and temperature rhythms associated with a very short tau. The trait segregates as an autosomal dominant with high penetrance. These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique opportunity for genetic analysis of human circadian physiology.

Activity Cycles↗
PubMed1998

Extraocular circadian phototransduction in humans.

Physiological and behavioral rhythms are governed by an endogenous circadian clock. The response of the human circadian clock to extraocular light exposure was monitored by measurement of body temperature and melatonin concentrations throughout the circadian cycle before and after light pulses presented to the popliteal region (behind the knee). A systematic relation was found between the timing of the light pulse and the magnitude and direction of phase shifts, resulting in the generation of a phase response curve. These findings challenge the belief that mammals are incapable of extraretinal circadian phototransduction and have implications for the development of more effective treatments for sleep and circadian rhythm disorders.

Adult↗
PubMed1998

Relationships between sleep and body temperature in middle-aged and older subjects.

OBJECTIVES: Although changes in the circadian timing system are thought to be a major factor in the decline of sleep quality that often accompanies aging, few reports have actually examined this relationship in detail. Because some treatments for age-related insomnia are based on putative circadian changes, it is important to expand the limited database that specifically addresses this issue. This study examined age-related changes in sleep, and relationships between those sleep changes and alterations in the circadian timing system, in a group of middle-aged and older subjects. DESIGN: Sixty healthy men and women between the ages of 40 and 84 were studied. A subset of older subjects (< 65 years) had reported sleep disturbance for at least 1 year before participation. Polysomnography was obtained, and body core temperature was recorded continuously for 24 hours. All recordings took place in the Laboratory of Human Chronobiology, Department of Psychiatry, Cornell University Medical College. RESULTS: There were no differences in sleep quality between middle-aged and non-sleep-disturbed older subjects. However, timing of the minimum body temperature was earlier in the older non-sleep-disturbed subjects than in the middle-aged group. In contrast, sleep-disturbed older people had shorter total sleep times, reduced sleep efficiency, more waking time after sleep onset, and a reduced proportion of REM sleep compared with non-sleep-disturbed older subjects. Yet, there were no differences between the two older groups in the rhythm of body temperature. For the entire group, age was correlated negatively with total sleep time, sleep efficiency, percentage of stage 2 sleep, and the timing of the temperature minimum. CONCLUSION: The results support the widely held notion that sleep and circadian rhythm changes occur with aging. However, the hypothesis that age-related changes in sleep may be associated with aging of the circadian system was supported only to a limited degree, suggesting that age-related sleep disturbance is likely to have multiple causes. Thus, treatment strategies that incorporate a combination of interventions may be the most effective.

Adult↗
PubMed1997

Ultrastructure and synthesis of the extracellular matrix of Pisaster ochraceus embryos preserved by freeze substitution.

When asteroid embryos cryoprotected with propylene glycol are rapidly frozen in liquid propane and freeze substituted with ethanol, preservation of the cells and extracellular matrix (ECM) is excellent. The basal lamina, although thicker and less well defined than in conventionally fixed embryos, demonstrates a region of decreased density just below the cells that corresponds to the lamina lucida and a lamina densa. The former region is often occupied by fibrous material. In addition, as was previously described in conventionally fixed issues, the basal lamina of the ectoderm is generally thicker and more substantial than that of the endoderm, reinforcing an earlier suggestion that the structure of the basal is different in different regions of the embryo. The ECM of the blastocoel consists of thin "twig-like" elements that form a loose meshwork evenly distributed throughout the blastocoel. Bundles of 20 nm fibers, located within the meshwork, are oriented parallel to the base of the cells of the stomodeum. In the long axis of the embryo, similar fibers are present in the dorsal aspect of the animal between the stomach and the ectoderm and radiate out from the esophagus crossing the region between it and the ectoderm. Immunocytochemical work with three different monoclonal antibodies shows that glycoprotein molecules, synthesized in the Golgi apparatus, are also secreted here and form part of the matrix structure. The results suggest that the blastocoel is filled with a gel-like material reinforced with bundles of 20-nm fibers. The manner in which the observed arrangement could contribute to the development and maintainence of the shape of the embryo is discussed.

Animals↗
PubMed1997

Nighttime drop in body temperature: a physiological trigger for sleep onset?

Relationships between changes in the slope of the body temperature (BT) and the initiation of sleep were examined in 44 subjects ranging from 19 to 82 years of age. Following an adaptation night, subjects remained in the laboratory for a baseline night and 72 hours in temporal and social isolation, with strictly limited behavioral options ("disentrainment") during which continuous electroencephalograph (EEG) and BT were recorded. Polysomnographic sleep variables (e.g. sleep onset, percentage of each sleep stage) were determined for nighttime sleep periods at baseline and during the disentrainment period. Periods of the BT curve surrounding these sleep bouts were examined for minute to minute changes, and the time at which the maximum rate of decline (MROD) in temperature occurred was compared with the time of sleep onset (SO) and sleep quality parameters. On the baseline night, the MROD occurred, on average, 60 minutes prior to SO. During disentrainment, the MROD occurred, on average, 44 minutes prior to SO. The proximity of MROD to SO did not affect subsequent sleep quality on the baseline night, but during disentrainment, there were significant correlations between the interval from MROD to sleep onset and the amount of slow-wave sleep (SWS) obtained during the sleep bout. There were no significant age differences on variables related to MROD on baseline night, but the timing of both MROD and SO were significantly advanced in older, relative to younger, subjects during the disentrainment period. It is suggested that a rapid decline in core body temperature increases the likelihood of sleep initiation and may facilitate an entry into the deeper stages of sleep.

Adult↗
PubMed1996

Enhanced performance in elderly subjects following bright light treatment of sleep maintenance insomnia.

Sixteen older individuals with sleep maintenance insomnia were treated with night-time bright-light exposure (BL) while living at home. Twelve consecutive days of acute light treatment were followed by a 3-mo maintenance light-treatment period. Subjects completed laboratory evaluation sessions on five separate occasions (prior to and following the acute light-treatment period, and once per month during the maintenance period). During each laboratory session, performance levels, sleep, and core body temperature were measured. The performance battery consisted of four computerized tasks (Logical Reasoning, Stroop Congruency, Two Letter Visual Search, and Wilkinson Four-Choice Reaction Time) and was administered every 2 h between 10.00 and 18.00 hours. Subjects improved significantly on three of the four tasks from pre-BL to post-BL. During the maintenance period, subjects who received active BL treatment maintained significantly higher performance levels than a control BL group. Light treatment improved sleep efficiency and delayed the phase of the body temperature rhythm. Performance improvements were significantly related only to sleep and not to circadian phase. The implications for non-circadian treatments of sleep maintenance insomnia and cognitive functioning in the elderly are discussed.

Aged↗
PubMed1996

Physiology of the circadian system in animals and humans.

Virtually all organisms have developed an internal timing system capable of reacting to and anticipating environmental stimuli with a program of appropriately timed metabolic, physiologic, and behavioral events. The predominant biological rhythms coincide with the geophysical cycle of day and night-the circadian rhythms. The suprachiasmatic nuclei comprise the primary pace-maker in mammals, exhibiting the properties fundamental to a rhythm-generating structure. This article summarizes recent research that has elucidated mechanisms of signal transduction within the circadian system. The roles of various neurochemicals and hormones in transmitting the circadian timing signal are described. Properties of the circadian system, including photic and nonphotic entrainment, phase response curves, masking, and the intrinsic variability in the system are discussed.

Animals↗
PubMed1995

Effects of timed bright-light exposure on shift-work adaptation in middle-aged subjects.

Shift workers suffer from a constellation of symptoms that can severely compromise their ability to perform optimally on-shift. The largest single factor contributing to shift-worker problems is sleep disturbance, and there is little question that the primary cause of such sleep disturbance is circadian disruption. Recently, a number of studies have demonstrated that timed exposure to bright light can help facilitate adaptation to simulated shift-work schedules, at least in younger subjects. The aim of the current study was to assess the effects of bright-light interventions in middle-aged individuals undergoing a simulated shift-work regimen. Results indicate that although light was effective in resetting the circadian clocks of these subjects by more than 6 hours, there was little effect on measures of on-duty alertness and performance or on off-duty sleep. These findings suggest that middle-aged subjects may be less phase-tolerant than young subjects, and they raise questions concerning the utility of bright-light interventions in some shift-work populations.

Adult↗