Biomedical subjects

A W Kirby

Publications and source records attributed to A W Kirby.

14 recordsLinked to original sources

PubMed1999

Melatonin and the reduction or alleviation of stress.

In a double blind and placebo controlled study designed to investigate the effect of melatonin administration at 13:00 hr on menstrual characteristics, prolactin, and premenstrual syndrome-like symptoms during simulated eastward travel, it was noted that melatonin reduces or alleviates the stress associated with the simulated travel. Bright lights were utilized to simulate eastward movement across six time zones. Melatonin (10 mg) was given to healthy females for 5 consecutive days during the late follicular and early luteal phases of the menstrual cycle. Hourly blood samples, used for analysis of melatonin and prolactin levels, were obtained for 24 hr before entering the dose administration phase of the study and again on the last dose day. Volunteers also completed a profile of moods state questionnaire upon waking on each of 8 days which overlapped the in-house dose administration days. The placebo group showed a prolactin peak at 13:00 hr (dose time) on the last dose day/blood draw, while the melatonin group showed a prolactin peak at 15:00 hr. The prolactin peak at 13:00 hr is likely the result of stress, since stress is known to elicit the release of prolactin. The peak at 15:00 hr in the melatonin group was likely elicited by the administration of melatonin. Stress reduction in the melatonin group was supported by results from the profile of moods state questionnaire. The melatonin group consistently demonstrated scores indicative of less stress.

Adolescent↗

PubMed1997

Triple-helical DNA as a reversible block of the branch point in a partially symmetrical DNA four-arm junction.

DNA branch migration is a fundamental process in genetic recombination. A new model system has been developed for studying branch migration in a small synthetic four-arm junction. A mathematical method for describing branch-point movement by discrete steps in such junctions is also presented. The key to our experimental system is the ability to fix the location of the branch point during the assembly of the junction with a reversible block. The block is provided by a short oligonucleotide that forms triplex DNA adjacent to the initial location branch point at low pH. Raising the pH causes the triplex strand to dissociate, making the branch point free to migrate. Once mobile, the branch point can run off the end of the junction. The time-course for this runoff is consistent with a random walk of the branch point. If it is assumed that one migration step moves the branch point one base-pair, the time-course gives a rate constant for one step of 1.4 second-1 at 37 degrees C in 10 mM MgCl2, 50 mM NaCl. These values are consistent with other measurements of non-enzymatic branch migration. We have also monitored the spread of the branch points directly with T4 endonuclease VII. Using EcoRI restriction endonuclease, we have shown that the binding of this protein to the arms of the junction essentially blocks branch migration through the binding site. In these experiments Ca2+ replaces Mg2+, and the enzyme does not cleave the DNA. In vivo there must be a special process to get branch points to migrate past bound proteins.

DNA↗

PubMed1996

Melatonin efficacy in aviation missions requiring rapid deployment and night operations.

BACKGROUND: The rapid deployment of Army aviation personnel across time zones, combined with missions beginning immediately upon arrival, results in desynchronization of physiological and cognitive performance rhythms. Implementation of effective countermeasures enhances safety, health, well-being, and mission completion. The naturally occurring hormone melatonin has been suggested as an effective counter measure for jet lag and shift lag because of its influence on the human circadian timing system and its hypnotic properties. METHODS: The efficacy of melatonin (10 mg) in maintaining stable sleep/wake cycles of Army aircrews was tested during a training mission involving rapid deployment to the Middle East and night operations. Cognitive performance was tested before and after travel; activity rhythms were recorded continuously for 13 d. RESULTS: Melatonin treatment advanced both bedtimes and rise times (2-3 h) and maintained sleep durations between 7-8 h. Placebo treatment was mostly associated with longer advances in rise times than bedtimes resulting in shorter sleep durations (5-7 h). Upon awakening, the melatonin group exhibited significantly fewer errors (mean: 7.45) than the placebo group (mean: 14.50) in a dual-task vigilance test. CONCLUSION: Melatonin can be a useful treatment for the prevention of sleep disruptions and cognitive degradation, even in uncontrolled sleeping environments characteristic of military deployments.

Adult↗

PubMed1991

Effect of diisopropylfluorophosphate on muscarinic and gamma-aminobutyric acid receptors in visual cortex of cats.

Administration of diisopropylfluorophosphate (DFP), an organophosphorus (OP) compound, irreversibly inhibits acetylcholinesterase (AChE) and results in cholinergic hyperactivity. This study investigated muscarinic and gamma-aminobutyric acid (GABA) receptor changes in visual cortex of cats following an acute exposure to DFP. A single acute administration of DFP (4 mg/kg) decreased the number of muscarinic receptors at 2, 10, and 20 hours after treatment. GABA receptors were elevated at 2 and 10 hours but returned to within control levels at 20 hours. No significant alteration in muscarinic or GABA receptor affinity was noted. In all cases cortical AChE activity was inhibited 60-90%. These findings show a down regulation of muscarinic receptors after DFP associated with low AChE activity. GABA receptors also are altered, and may be part of a compensatory mechanism to counteract excess cholinergic stimulation.

Acetylcholinesterase↗

PubMed1987

Recovery of the visual evoked response in the cat following administration of diisopropylfluorophosphate, an irreversible cholinesterase inhibitor.

Visual evoked responses (VER) to counterphased gratings were recorded from area 17 of cat visual cortex prior to and following administration of diisopropylfluorophosphate (DFP). The VER and acetylcholinesterase (AChE) activity of blood, retina, and visual cortex were reduced significantly following DFP administration. Approximately two hours after exposure to 4 mg/kg DFP, the VER began to recover and in some cats returned to base line levels. In contrast, blood, retina, and cortex AChE activity showed little, if any, tendency for recovery throughout the experiment. Since atropine sulfate provided at least partial recovery of the VER following DFP without affecting AChE inhibition, an accumulation of acetylcholine (ACh) probably is involved in the initial visual loss. However, recovery of the VER over time while AChE remained severely inhibited implicates mechanisms other than, or in addition to, accumulation of ACh at receptor sites.

Acetylcholinesterase↗

PubMed1985

The effects of diisopropylfluorophosphate on spatial frequency responsivity in the cat visual system.

Visual-evoked responses to counterphased gratings were recorded from area 17 of cat visual cortex before and after diisopropylfluorophosphate (DFP) administration. DFP produced effects similar to those obtained following physostigmine sulfate administration, in that responses to low spatial frequencies were preferentially reduced. The time course of the effects was quite different for the two types of drugs, and for high doses of DFP responses to all spatial frequencies were approximately uniformly depressed or abolished.

Animals↗

PubMed1984

Contrast sensitivity determined with the spatial bandwidth equalization technique: threshold, suprathreshold, and spatiotemporal measurements.

Contrast sensitivity functions were obtained from normal subjects using a spatial bandwidth equalization (SBE) technique and the more conventional display method. Static sensitivity measurements obtained with the two methods were in good agreement. However, when the patterns were counterphase flickered , sensitivity to the lower spatial frequencies was enhanced using the conventional method while sensitivity measured with the SBE technique was slightly depressed. The SBE method also was used to investigate suprathreshold contrast perception with static and flickering gratings. In general, the perception of contrast was independent of spatial frequency content of the stimulus, especially with increasing contrast levels and flicker frequencies. These studies have shown that the SBE technique is an acceptable method to assess static contrast sensitivity and suprathreshold contrast perception.

Humans↗

PubMed1983

A cholinergic-sensitive channel in the cat visual system tuned to low spatial frequencies.

Visually evoked responses to counterphased gratings were recorded from the cat visual cortex before and after physostigmine administration. Physostigmine markedly reduced the responses to low spatial frequencies, but minimally affected the response to high frequencies. This effect is considered cholinergic since it could be reversed by atropine. These results support at least a two-channel model of spatial frequency responsivity.

Animals↗

PubMed1982

Elongation of cat eyes following neonatal lid suture.

Development of the axial length of cat eyes was monitored through A-scan ultrasonography at various times after neonatal monocular lid suture. In every case the deprived eye was longer than its fellow eye. Upon reestablishment of the palpebral fissure, refractive state and corneal curvature were recorded. Although all the deprived eyes showed axial elongation, there was no consistent relationship between neonatal lid fusion and the degree of myopia.

Age Factors↗

PubMed1981

GABA-antagonists and spatial summation in Y-type cat retinal ganglion cells.

1. The effect of GABA-antagonists on centre size of Y-type retinal ganglion cells was measured under conditions which ensured that cells were rod driven. 2. Both bicuculline and picrotoxin, administered intravenously, led to reliable and reversible changes in centre size as determined by area-sensitivity measurements. 3. The administration of GABA-antagonists produced opposite results in on- and off-centre cells; the centre summing area decreased in on-centre cells and increased in off-centre cells.

Animals↗

PubMed1981

Gaba-antagonists alter spatial summation in receptive field centres of rod- but not cone-drive cat retinal ganglion Y-cells.

1. When Y-type cat retinal ganglion cells were driven by cones, the i.v. administration of the GABA-antagonist picrotoxin failed to alter receptive field centre size. 2. This result is in marked contrast to our previous finding that when Y-cells were driven by rods, GABA-antagonists led to specific and reversible changes in centre size. 3. These results taken together suggest that for centre signals of Y-cells, the rod and cone pathways are pharmacologically distinct.

Animals↗

PubMed1979

The effect of strychnine, bicuculline, and picrotoxin on X and Y cells in the cat retina.

The effect of intravenous strychnine and the GABA antagonists picrotoxin and bicuculline upon the discharge pattern of center-surround-organized cat retinal ganglion cells of X and Y type were studied. Stimuli (mostly scotopic, and some photopic) were selected such that responses from both on and off-center cells were either due to the center, due to the surround, or clearly mixed. Pre-drug control responses were obtained, and their behavior following administration of the antagonists was observed for periods up to several hours. X-cell responses were affected in a consistent manner by strychnine while being unaffected by GABA antagonists. All observed changes following strychnine were consistent with a shift in center-surround balance of X cells in favor of the center. For Y-cell responses to flashing annuli following strychnine, there was either no shift or a relatively small shift in center-surround balance. Compared to X-cell responses to flashing lights, those of Y cells were very little affected by strychnine and in most cases were unaffected. It thus appears that glycine plays a similar role in receptive field organization of X cells as does GABA in Y cells (Kirby and Enroth-Cugell, 1976. J. Gen. Physiol. 68:465-484).

Action Potentials↗

PubMed1978

Square wave jerks in Friedreich's ataxia.

We observed a brother and sister with Friedreich's ataxia during steady fixation. They both had abnormal eye movements consisting of randomly occurring, small amplitude, conjugate horizontal saccades away from the fixation target. The saccades were followed by maintenance of this eccentric position for a brief period, and finally, a corrective saccade back to the original position. Electro-oculographic recordings showed these eye movements to be square wave jerks. They had an amplitude ranging from 1.5 to 10.7 degrees and a duration averaging less than 200 msec. Square wave jerks were also superimposed on pursuit movements in both patients. Square wave jerks are an additional ocular finding that may signify chronic cerebellar dysfunction. More specifically, they are an additional neuro-ophthalmological finding that may be observed in Friedreich's ataxia.

Adolescent↗

PubMed1976

The involvement of gamma-aminobutyric acid in the organization of cat retinal ganglion cell receptive fields. A study with picrotoxin and bicuculline.

The effects of picrotoxin and bicuculline upon the discharge pattern of center-surround organized cat retinal ganglion cells of X and Y type were studied. All experiments were carried out under scotopic or possibly low mesopic conditions; mostly but not exclusively on-center cells were studied. Stimuli were chosen so that responses were either; (a) "purely" central; (b) surround dominated; or (c) clearly mixed but center dominated. In each case a pre-drug control response was estaboished, the drug was administered intravenously, and its subsequent effect upon the response was observed. In Y cells both picrotoxin and bicucullin caused the center-driven component of the response to become somewhat reduced in magnitude, while the surround component was substantially reduced. There was thus a change in center-surround balance in favor of the center-driven component. Responses of X cells remained virtually unaffected by both picrotoxin and bicuculline.

Adaptation, Physiological↗