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Biomedical subjects

M E Harrington

Publications and source records attributed to M E Harrington.

At least 19 recordsLinked to original sources
PubMed1997

Circadian phase shifts to neuropeptide Y In vitro: cellular communication and signal transduction.

Mammalian circadian rhythms originate in the hypothalamic suprachiasmatic nuclei (SCN), from which rhythmic neural activity can be recorded in vitro. Application of neurochemicals can reset this rhythm. Here we determine cellular correlates of the phase-shifting properties of neuropeptide Y (NPY) on the hamster circadian clock in vitro. Drug or control treatments were applied to hypothalamic slices containing the SCN on the first day in vitro. The firing rates of individual cells were sampled on the second day in vitro. Control slices exhibited a peak in firing rate in the middle of the day. Microdrop application of NPY to the SCN phase advanced the time of peak firing rate. This phase-shifting effect of NPY was not altered by block of sodium channels with tetrodotoxin or block of calcium channels with cadmium and nickel, consistent with a direct postsynaptic site of action. Pretreatment with the glutamate receptor antagonists (DL-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione disodium) also did not alter phase shifts to NPY. Blocking GABAA receptors with bicuculline (Bic) had effects only at very high (millimolar) doses of Bic, whereas blocking GABAB receptors did not alter effects of NPY. Phase shifts to NPY were blocked by pretreatment with inhibitors of protein kinase C (PKC), suggesting that PKC activation may be necessary for these effects. Bathing the slice in low Ca2+/high Mg2+ can block phase shifts to NPY, possibly via a depolarizing action. A depolarizing high K+ bath can also block NPY phase shifts. The results are consistent with direct action of NPY on pacemaker neurons, mediated through a signal transduction pathway that depends on activation of PKC.

2-Amino-5-phosphonovalerate↗
PubMed1997

NPY opposes PACAP phase shifts via receptors different from those involved in NPY phase shifts.

The suprachiasmatic nuclei (SCN) of the hamster can be maintained for several days in vitro, allowing electrophysiological investigation of the mammalian circadian clock. Application of pituitary adenylate cyclase activating peptide (PACAP) at Zeitgeber time (ZT) 6 on the first day in vitro can phase shift the rhythm of firing rate expressed by SCN neurons on a subsequent day in vitro. Here we report that co-application of neuropeptide Y (NPY) will block the phase-shifting action of PACAP. This blocking action is mimicked by [Leu31,Pro34]NPY and [D-Trp32]NPY but not by NPY(22-36) or avian pancreatic polypeptide. The results indicate that NPY has actions in the SCN via receptors distinct from the Y2 receptor, which mediates the phase-shifting action of NPY.

Animals↗
PubMed1997

A classification system to evaluate weight maintainers, gainers, and losers.

OBJECTIVES: To study natural weight changes and to develop a weight classification system that can identify weight maintainers, gainers, and losers. DESIGN/OUTCOME: A prospective, observational study in which weight changes over five annual measurements were evaluated. In the weight classification system used, changes greater than 5 lb defined weight maintenance, gain, or loss. SUBJECTS/SETTINGS: Subjects were healthy, normal-weight and over weight, men and women (mean age = 44.1 +/- 14.1 years) in the Relationships of Energy, Nutrition, and Obesity to Cardiovascular Disease Risk Study. Prospective data for 385 of the original 508 subjects for whom actual weights were available for each of the 5 years (1985 to 1990) were used to classify and characterize subjects by weight-change categories. STATISTICAL ANALYSES: Cross-tabulations (with chi 2 tests) and hterarchical log-linear analyses (with partial chi 2 tests) to examine the relationships of categorical variables; analyses of variance (with F tests) for continuous measures. RESULTS: Over the 4-year interval, 46% of subjects were classified as maintainers, 34% as gainers, and 20% as losers. Over shorter 1-year epochs, more subjects were maintainers (62%) and fewer subjects were gainers (22%) or losers (16%). Maintainers had fewer and smaller magnitudes of weight fluctuations and showed fewer deleterious changes in health risk factors than gainers. APPLICATIONS: Weight changes of greater than +/-5 lb can classify a person as a weight maintainer, or loser. Although annual weight changes were used in this study, a weight change of more than 5 lb between any two points in time may suggest nonmaintenance of weight or weight instability that needs further evaluation.

Adult↗
PubMed1997

The ventral lateral geniculate nucleus and the intergeniculate leaflet: interrelated structures in the visual and circadian systems.

The ventral lateral geniculate nucleus (vLGN) and the intergeniculate leaflet (IGL) are retinorecipient subcortical nuclei. This paper attempts a comprehensive summary of research on these thalamic areas, drawing on anatomical, electrophysiological, and behavioral studies. From the current perspective, the vLGN and IGL appear closely linked, in that they share many neurochemicals, projections, and physiological properties. Neurochemicals commonly reported in the vLGN and IGL are neuropeptide Y, GABA, enkephalin, and nitric oxide synthase (localized in cells) and serotonin, acetylcholine, histamine, dopamine and noradrenalin (localized in fibers). Afferent and efferent connections are also similar, with both areas commonly receiving input from the retina, locus coreuleus, and raphe, having reciprocal connections with superior colliculus, pretectum and hypothalamus, and also showing connections to zona incerta, accessory optic system, pons, the contralateral vLGN/IGL, and other thalamic nuclei. Physiological studies indicate species differences, with spectral-sensitive responses common in some species, and varying populations of motion-sensitive units or units linked to optokinetic stimulation. A high percentage of IGL neurons show light intensity-coding responses. Behavioral studies suggest that the vLGN and IGL play a major role in mediating non-photic phase shifts of circadian rhythms, largely via neuropeptide Y, but may also play a role in photic phase shifts and in photoperiodic responses. The vLGN and IGL may participate in two major functional systems, those controlling visuomotor responses and those controlling circadian rhythms. Future research should be directed toward further integration of these diverse findings.

Animals↗
PubMed1997

Neuropeptide Y and glutamate block each other's phase shifts in the suprachiasmatic nucleus in vitro.

The suprachiasmatic nuclei contain a circadian clock whose activity can be recorded in vitro for several days. Photic information is conveyed to the nuclei primarily via a direct projection from the retina, the retinohypothalamic tract, utilizing an excitatory amino acid neurotransmitter. Photic phase shifts may be mimicked by application of glutamate in vitro. A second, indirect pathway to the suprachiasmatic nuclei via the geniculohypothalamic tract utilizes neuropeptide Y as a transmitter. Phase shifts to neuropeptide Y in vitro are similar to those seen to non-photic stimuli in vivo. We have used the hypothalamic slice preparation to examine the interactions of photic and non-photic stimuli in the suprachiasmatic nuclei. Coronal hypothalamic slices containing the suprachiasmatic nuclei were prepared from Syrian hamsters and 3 min recordings of the firing rate of individual cells were performed throughout a 12 h period. Control slices receiving either no application or application of artificial cerebrospinal fluid to the suprachiasmatic nucleus showed a consistent daily peak in their rhythms. Glutamate produces phase shifts of the circadian clock in the hamster hypothalamic slice preparation during the subjective night but not during the subjective day. These phase shifts were similar in timing and direction to the photic phase response curve in vivo confirming previous work with the rat slice preparation. Neuropeptide Y produces phase shifts of the circadian clock during the subjective day but not during the subjective night. The phase shifts are similar in timing and direction to the non-photic phase response curve in vivo, confirming previous in vitro work. We then examined the interaction of these neurochemicals with each other at various times during the circadian cycle. We found that both advances and delays to glutamate in the slice are blocked by application of neuropeptide Y. We also found that phase shifts to neuropeptide Y in the slice are blocked by application of glutamate. These results indicate that photic and non-photic associated neurochemicals can block each others phase shifting effects within the suprachiasmatic nucleus in vitro. These experiments demonstrate the ability of photic and non-photic associated neurochemicals to interact at the level of the suprachiasmatic nucleus. It is clear that neuropeptide Y antagonizes the effect of glutamate during the subjective night, and that glutamate antagonizes the effect of neuropeptide Y during the subjective day. Great care must be taken when devising treatments where photic and non-photic signals may interact.

Animals↗
PubMed1997

Suprachiasmatic nucleus neurons are glucose sensitive.

The suprachiasmatic nucleus (SCN) in the hypothalamus serves as the pacemaker for mammalian circadian rhythms. In a hamster brain slice preparation, the authors were able to record spontaneous activity from SCN cells for up to 4 days in vitro and verify a self-sustained rhythm in firing. The phase of this rhythm was altered by the concentration of glucose in the bathing medium, with time of peak firing advanced for a 20 mM glucose condition and slightly delayed for a 5 mM glucose condition, relative to 10 mM. The advancing effect of 20 mM glucose and the delaying effect of 5 mM glucose were not maintained during a 2nd day in vitro after changing the bathing medium back to 10 mM glucose, thus indicating the effect was not a permanent phase shift of the underlying oscillation. In experiments recording from cell-attached membrane patches on acutely dissociated hamster SCN neurons, exchanging the bathing medium from high (20 mM) to zero glucose increased potassium (K+)-selective channel activity. With inside-out membrane patches, the authors revealed the presence of a glybenclamide-sensitive K+ channel (190 pS) and a larger conductance (260 pS) Ca(2+)-dependent K+ channel that were both reversibly inhibited by ATP at the cytoplasmic surface. Furthermore, 1 mM tetraethylammonium chloride was demonstrated to advance peak firing time in the brain slice in a similar manner to a high concentration of glucose (20 mM). The authors interpret the result to imply that SCNs are sensitive to glucose, most probably via ATP modulation of K+ channel activity in these neurons. Tonic modulation of K+ channel activity appears to alter output of the pacemaker but does not reset the phase.

Adenosine Triphosphate↗
PubMed1997

Aedes aegypti in Córdoba Province, Argentina.

In 1955, the area infested by Aedes aegypti in Argentina was estimated as 1,500,000 km2; and in 1963, the species was considered to be eradicated from Argentina. In 1995, the Argentine Ministry of Health reported reinfestation by Ae. aegypti. During 1994-95, the Ministry of Health of Córdoba Province, Zoonosis Department, established a surveillance system for Ae. aegypti in Córdoba Province, Argentina. This report is a summary of results obtained thus far. In total, 74 localities in Córdoba Province were sampled during August 1994-April 1996, resulting in 5 positives (6.7%): Villa María city, Villa Nueva, and Córdoba city in 1995, and Juarez Celman and Jesús María in 1996. In Villa María and Villa Nueva, Ae. aegypti was present until June 1995 (autumn) and reappeared in December 1995. In Córdoba city, Ae. aegypti was eliminated from the only positive house in May 1995, but it reappeared in March 1996. Reappearance of Ae. aegypti in this temperate area in early summer may have been due to the survival of individuals during winter and not to reintroduction during summertime. The last previous active surveillance for Ae. aegypti in Córdoba Province was carried out more than 30 years ago.

Aedes↗
PubMed1996

Neuropeptide Y phase shifts the circadian clock in vitro via a Y2 receptor.

The suprachiasmatic nuclei (SCN) contain a circadian clock whose activity can be recorded in vitro for several days. This clock can be reset by the application of neuropeptide Y. In this study, we focused on determination of the receptor responsible for neuropeptide Y phase shifts of the hamster circadian clock in vitro. Coronal hypothalamic slices containing the SCN were prepared from Syrian hamsters housed under a 14 h:10 h light:dark cycle. Tissue was bathed in artificial cerebrospinal fluid (ACSF), and the firing rates of individual cells were sampled throughout a 12 h period. Control slices received either no application or application of 200 nl ACSF to the SCN at zeitgeber time 6 (ZT6; ZT12 was defined as the time of lights off). Application of 200 ng/200 nl of neuropeptide Y at ZT6 resulted in a phase advance of 3.4 h. Application of the Y2 receptor agonist, neuropeptide Y (3-36), induced a similar phase advance in the rhythm, while the Y1 receptor agonist, [Leu31, Pro34]-neuropeptide Y had no effect. Pancreatic polypeptide (rat or avian) also had no measurable phase-shifting effect. Neuropeptide Y applied at ZT20 or 22 had no detectable phase-shifting effect. These results suggest that the phase-shifting effects of neuropeptide Y are mediated through a Y2 receptor, similar to results found in vivo.

Animals↗
PubMed1996

Circadian rhythm photic phase shifts are not altered by histamine receptor antagonists.

Histamine may play a role in synchronizing endogenous circadian rhythms with exogenous photic cues. Direct application of histamine to the suprachiasmatic nucleus, the site of the mammalian circadian pacemaker, phase shifts the circadian rhythm in neural activity [7]. Intraventricular injections of histamine also phase shift circadian rhythms [14]. The magnitude and direction of the phase shifting effects of histamine depend on circadian phase in a manner similar to light [7,14]. Depletion of brain histamine levels by inhibition of histamine synthesis reduces phase shifts to light [10].

Animals↗
PubMed1995

Histamine synthesis inhibition reduces light-induced phase shifts of circadian rhythms.

Circadian rhythms are generated by the hypothalamic suprachiasmatic nuclei, a site of dense histaminergic innervation. Histamine can phase shift circadian rhythms in a manner similar to light. In this experiment, we administered alpha-fluoromethylhistidine (FMH), an inhibitor of histamine synthesis, prior to a light pulse in hamsters housed under constant darkness. Photic phase shifts in wheel-running rhythms were significantly attenuated by FMH pretreatment. These results suggest that histamine may modulate photic input to the circadian clock.

Animals↗
PubMed1995

Who are the weight maintainers?

To characterize people who maintain weight over long periods of time, normal weight and obese adults (n = 385) were studied over five annual visits. Subjects were classified using a +/- 5 lb change between the first and the fifth year visits to determine overall maintenance (M), with gain (G) or loss (L) being any change outside this range. This MGL status was cross-tabulated with a Fluctuation Index which counted the number of successive year-to-year weight changes of more than +/- 5 lbs (F0 through F4). True maintainers were defined as those having all weight changes within +/- 5 lbs during the 5-year period (M and F0). Nineteen percent (n = 73) of the subjects were classified as True Maintainers and included three times as many normal weight as obese subjects. Obese subjects comprised only 25% of the True Maintainer group but 60% of the Non-Maintainer group. Age had no association with Maintainer status. Standard measures of weight variability were lowest among True Maintainers and highest in Non-Maintainers. In addition, True Maintainers had lower BMI, Percent Body Fat, and Waist-Hip Ratios than Non-Maintainers. Subjects classified as Non-Maintainers were more likely to engage in dieting, by a variety of measures, than True Maintainers--this was particularly true among obese subjects. Finally, changes in total cholesterol, LDL and HDL cholesterol, and systolic and diastolic blood pressure were not reliably associated with Maintainer status, although the ordering of the group means suggested that True Maintainers had slightly healthier levels of "risk" variables. Overall, the results suggest that True Maintainers comprise a potentially important and interesting group of individuals who need further study.

Adult↗
PubMed1995

A measurement system for the recognition of arm gestures using accelerometers.

This paper describes a strategy to measure arm movements using accelerometers for the computer recognition of arm gestures. Gesture recognition is being investigated as an alternative method of computer input for people with severe speech and motor impairment; the emphasis is on the needs of people with athetoid cerebral palsy who have difficulties with existing computer input devices. An initial model-based approach to estimate the kinematic motion of the arm from acceleration measurements is given, followed by the chosen measurement scheme. The current system considers the forearm as a rigid body and uses two data streams derived from four linear accelerometers. By treating these signals as outputs from postulated mechanical models, the data are reduced to two series of step inputs that are appropriate for pattern classification and recognition. Although this does not in any way model the arm, the concepts used are based on the type of driving signals expected in the control of arm gestures. Initial experimental results show that the information content of gestures is preserved by this data parameterization.

Arm↗
PubMed1994

Axillofemoral bypass: compromised bypass for compromised patients.

PURPOSE: The procedure of axillofemoral bypass (AXF) grafting has generally been used in the past for patients with serious contraindication to certain reconstructive procedures involving the abdominal aorta. Because some recent series have noted improved results, it has been suggested that the indications for this bypass may be extended. We reviewed our experience with AXF to identify which factors affect outcome, to determine whether recent results have improved, and to determine whether an extension of the use of the procedure is justified by the observed results. METHOD: One hundred fifty-three AXF, including 80 axillobifemoral bypasses and 73 axillounifemoral bypasses performed between October 1974 and December 1992 were reviewed. RESULTS: Three-year primary and secondary patency rates for the entire group were 49.4% and 65.7%. Primary patency was adversely affected (p < 0.05) by superficial femoral artery occlusion, use of externally supported polytetrafluoroethylene, distal endarterectomy, distal anastomosis to the deep femoral artery, and year of surgery after 1984, but not by use of unifemoral or bifemoral outflow, side of graft origin, or concomitant distal procedure. The operative mortality rate of bypasses performed for claudication and the limb salvage rate was 8.3% overall and 5.9% after 1984. Limb salvage rates were 74.8% and 74.8% at 3 and 5 years. The patient survival rate for all AXF was 55.8% and 39.2% at 3 and 5 years. AXF for acute ischemia carried a high rate of mortality and limb loss. CONCLUSION: Bifemoral outflow, external support, and more recent surgery were not associated with improved patency rates. Our results do not support extended indications for AXF.

Aged↗
PubMed1993

Histamine phase shifts the circadian clock in a manner similar to light.

The mammalian circadian pacemaker in the suprachiasmatic nuclei (SCN) receives a dense input from histamine-containing neurons in the posterior basal hypothalamus. We applied histamine to SCN tissue in vitro and measured the subsequent rhythm in firing rate. Histamine caused a phase delay in the early subjective night and a phase advance in the late subjective night. The similarity of histamine- and photic-induced phase shifts indicates that histamine may play a role in the modulation of circadian clock photic input.

Action Potentials↗
PubMed1993

A phase-response curve to the benzodiazepine chlordiazepoxide and the effect of geniculo-hypothalamic tract ablation.

The geniculo-hypothalamic tract (GHT) provides input to the mammalian circadian pacemaker in the suprachiasmatic nucleus. Several recent reports indicate that GHT ablation blocks phase shifts to the benzodiazepines triazolam and chlordiazepoxide at circadian times (CTs) 6 and 21. In this study we tested if GHT ablation blocks phase shifts to chlordiazepoxide at a wide range of circadian phases. Syrian hamsters were housed under constant dim light, and running-wheel activity rhythms were monitored. Intraperitoneal injections of either chlordiazepoxide (100 mg/kg) or saline were administered at various circadian times, and a phase-response curve was constructed. In intact animals, chlordiazepoxide produced phase-advance shifts at CTs 0, 4, 6, and 8, and phase-delay shifts between CTs 12-14. Although bursts of increased activity were sometimes observed on the day of injection, activity does not appear to mediate chlordiazepoxide-induced phase shifts. Hamsters with > 45% GHT ablation showed no phase shifts > 20 min to chlordiazepoxide. Our results indicate that the geniculo-hypothalamic tract is necessary for the phase-shifting effects of the benzodiazepine chlordiazepoxide throughout the circadian cycle.

Animals↗
PubMed1993

Effects of damage to SCN neurons and efferent pathways on circadian activity rhythms of hamsters.

This experiment was designed to determine if entrainment to a light:dark (LD) schedule and the free-running rhythm in constant light are altered by partial lesions of suprachiasmatic nuclei (SCN) cells or SCN output pathways. Twenty-four male golden hamsters were housed under 12L:12D. Hamsters received either lesions (n = 16), sham surgery (n = 4), or no surgery (n = 4), and were placed into individual cages with running wheels under 14L:10D. Each time after 4 weeks, the LD schedule was phase advanced by 6 h, phase delayed by 6 h, and then the animals were exposed to constant dim light. At the end of the experiment, brain sections were processed for peptide histidine isoleucine (PHI) and gastrin releasing peptide (GRP) immunohistochemistry. Alternate sections were stained for cells and fibers. Behavioral results indicate that (a) very few SCN cells and SCN efferent fibers, as labeled by PHI and GRP immunohistochemistry, are necessary for the expression of circadian rhythmicity in wheel running, and (b) damage to pathways rostral to the SCN may be more critical for entrainment and rhythmicity than damage to caudal pathways. Targets of PHI- and GRP-immunoreactive SCN efferent fibers were also identified.

Animals↗