Ten novel chicken dinucleotide repeat polymorphisms.
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Animals↗
Biomedical subjects
D Dawson
Publications and source records attributed to D Dawson.
Audit of direct access cardiac investigations: experience in an inner London Health District.
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Cardiology Service, Hospital↗
Effect of pegs and screws on bone ingrowth in cementless total knee arthroplasty.
The purpose of the present study was to assess the effects of pegs and screws on bone ingrowth into the tibial component in cementless total knee replacement. Left total knee replacements were performed in 21 mature male dogs with 3 cementless porous-coated tibial tray configurations (7 animals per group): (1) 4-peg design implanted with cortical screws passing through the pegs; (2) 4-peg design implanted without screws; and (3) pegless design secured by 4 cortical screws. The animals were allowed unrestricted activity and were euthanized 6 months postoperatively. The pegless components (Group 3) had the highest extent of bone ingrowth into the tray (90.3% +/- 9.4%), followed by the components with 4 pegs only (Group 2, 82.8% +/- 9.2%), and the components with 4 pegs and 4 screws (Group 1, 75.9% +/- 11.8%). The difference between Groups 1 and 3 was statistically significant (p < 0.05). The volume fraction of bone ingrowth in the tray did not differ among the 3 groups, with an overall mean of 22.5% (+/- 4.6%). At the posterolateral quadrant, Group 1 had significantly less bone ingrowth than Group 3 within the tray whether measured as the extent (63.6% +/- 20.5% versus 91.0% +/- 10.6%, p < 0.05) or volume fraction (19.1% +/- 8.8% versus 32.9% +/- 10.5%, p < 0.05). There were no between-group differences at the other quadrants. This study indicated that pegs provided no added benefit in a circumstance where sufficient initial fixation was obtained with screws.
Animals↗
Effects of post-mortem delay on high affinity forskolin binding sites and adenylate cyclase activity in rat and human striatum and cerebral cortex.
High affinity [3H]forskolin binding was measured using quantitative autoradiography in the striatum and frontal cortex of rat and human brain. Forskolin binding in rat striatum (310.8 +/- 26.0 pmol/g mean +/- S.E.M.) was approximately 4 times that in the frontal cortex (75.5 +/- 8.4 pmol/g), whereas in post-mortem human brain each region exhibited similar levels of forskolin binding (striatum 51.3 +/- 1.2 and cortex 53.2 +/- 2.1 pmol/g). Basal adenylate cyclase activity was assayed in membranes prepared from striatum and frontal cortex of rat and human; enzyme activity in the rat striatum was approximately 2-fold that in rat frontal cortex whereas enzyme activity in the human striatum was similar to that in the human frontal cortex. To investigate the effect of the interval between death and freezing of the brain, rats were killed by decapitation, then maintained at 37 degrees C for up to 4 hours before freezing and subsequent assay of forskolin binding and adenylate cyclase activity. Striatal forskolin binding declined markedly post-mortem such that 4 h post-mortem it was only 13% of the level in control animals while levels of cortical forskolin binding declined minimally during the immediate post-mortem period. Striatal and cortical adenylate cyclase activity (basal) was minimally influenced by post-mortem delay although in both regions there was a rapid loss of the ability of fluoroaluminate to stimulate adenylate cyclase. The data suggest that the striatum contains a population of high affinity forskolin binding sites which is extremely sensitive to post-mortem delay.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenylyl Cyclases↗
Pharmacological modification of glutamate neurotoxicity in vivo.
The ability of five agents (dizocilpine [MK-801], 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline [NBQX], enadoline [CI-977], L-nitroarginine methyl ester [L-NAME] and BW 1003c87) with well defined, distinct pharmacological profiles and with established anti-ischemic efficacy, to modify neuronal damage has been examined in a simple in vivo model of glutamate excitotoxicity. Cortical lesions were produced in physiologically-monitored halothane-anesthetised rats by reverse dialysis of glutamate. The volume of the lesion was quantified histologically by image analysis of approximately 20 sections taken at 200 microm intervals throughout the lesion. The AMPA and NMDA receptor antagonists (NBQX and MK-801) and the inhibitor of nitric oxide synthase (L-NAME) significantly reduced the lesion volume by a similar extent (by approximately 30% from vehicle). Two agents (the kappa opioid agonist, CI-977 and the sodium channel blocker, BW 1003c87) which putatively inhibit the release of endogenous glutamate presynaptically, had dissimilar effects on lesion size. CI-977 failed to alter the amount of damage produced by exogenous glutamate, whereas BW 1003c87 reduced the lesion size by approximately 50%. Using this model, the neuroprotective effects of anti-ischemic drugs can be explored in vivo, uncomplicated in contrast to experimental ischemia by reduced oxygen delivery, drug effects on tissue blood flow and compromised energy generation. In consequence, additional mechanistic insight into anti-ischemic drug action in vivo can be obtained.
Amino Acid Oxidoreductases↗
SID1-1: a mutation affecting meiotic sister-chromatid association in yeast.
Meiotic chromosome segregation must occur with high fidelity in order to prevent the generation of deleterious aneuploidies. In meiosis I, homologous chromosomes pair, then migrate to opposite poles of the spindle. This process uses a collection of unique structures and mechanisms that have yet to be thoroughly characterized. To acquire a collection of informative meiotic mutants, we carried out a novel genetic screen in Saccharomyces cerevisiae. This screen was designed to identify dominant mutants in which meiosis I chromosome segregation occurs with decreased fidelity. One mutant recovered using this screen, SID1-1 (sister disjunction), showed an incidence of spores disomic for a marked chromosome III that was 25-fold greater than the wild-type level. Crossing-over is slightly, but not dramatically, reduced in SID1-1. Both recombinant and nonrecombinant chromosomes segregate with reduced fidelity in the presence of SID1-1. We present evidence that the mutant is defective in sister-chromatid association.
Alleles↗
Serovar determination and molecular taxonomic correlation in Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum: a cooperative study of the International Working Group on Mycobacterial Taxonomy.
A cooperative study was conducted by the International Working Group on Mycobacterial Taxonomy to correlate the agglutination serovar designations of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum strains with the species ascriptions of these organisms according to molecular criteria and cultural properties and to assess the reproducibility of serovar determinations for a set of 63 reference strains of these species. Among the molecular criteria, the level of agreement between results obtained with nucleic acid probes and T-catalase serology results was 94% for strains of M. avium and M. intracellulare. Nucleic acid probes were not available for M. scrofulaceum, but none of the 10 strains ascribed to this species on the basis of catalase serology data reacted with a nucleic acid probe for M. avium or M. intracellulare. Ascription to a species on the basis of mycolic acid high-performance liquid chromatography patterns was in agreement with catalase serology results in 86% of the cases examined. Most strains belonging to serovars 1 through 6 and 8 through 11 were identified by molecular criteria as M. avium, most strains belonging to serovars 7, 12 through 20, 23, and 25 were identified as M. intracellulare, and most strains belonging to serovars 41 through 43 were identified as M. scrofulaceum, in agreement with common current practice. Evidence for assigning serovar 27 to M. scrofulaceum was obtained. However, two strains of a given serovar may, on occasion, be placed in different species. The dominant species assignments for strains belonging to serovars 21, 24, 26, and 28 remain unresolved.(ABSTRACT TRUNCATED AT 250 WORDS)
Agglutination Tests↗
Alleviation of sleep maintenance insomnia with timed exposure to bright light.
OBJECTIVE: Half of the population over 65 suffers from chronic sleep disturbance. As a consequence, almost 40% of hypnotic medications are prescribed to people over age 60. Yet, hypnotics are often of little benefit in this population. As such, an effective non-drug alternative could prove important in the management of age-related sleep maintenance insomnia. The current study sought to evaluate the efficacy of bright light exposure in the treatment of sleep maintenance insomnia. DESIGN: Following baseline sleep and circadian rhythms assessment, subjects with sleep-maintenance insomnia were treated with timed exposure to either bright white light or dim red light for 12 consecutive days. Sleep and circadian rhythms recordings were subsequently obtained and measures of sleep quality were compared to assess efficacy of the treatments. SETTING: Baseline and post-treatment sleep and circadian rhythms assessments took place in the Laboratory of Human Chronobiology, Department of Psychiatry, Cornell University Medical College. The treatment phase of the study was conducted in participants' homes. PARTICIPANTS: Sixteen men and women between the ages of 62 and 81 years were studied. All subjects were free of hypnotic medication, and all had experienced sleep disturbance for at least 1 year prior to entering the study. RESULTS: Exposure to bright light resulted in substantial changes in sleep quality. Waking time within sleep was reduced by an hour, and sleep efficiency improved from 77.5% to 90%, without altering time spent in bed. Increased sleep time was in the form of Stage 2 sleep, REM sleep, and slow wave sleep. The effects were remarkably consistent across subjects. CONCLUSIONS: The findings demonstrate the effectiveness of timed exposure to bright light in the treatment of age-related sleep maintenance insomnia. With further refinement of treatment regimens, this non-drug intervention may prove useful in a large proportion of sleep disturbed elderly.
Age Factors↗
Melatonin and sleep in humans.
Early studies on the physiological effects of melatonin typically reported hypnotic 'side-effects'. Later studies, specifically addressing this action, failed to reliably replicate hypnotic effects using standard polysomnography. This difference may be related to differences in the basic physiological action of melatonin compared with more conventional hypnotics. It is suggested that melatonin exerts a hypnotic effect through thermoregulatory mechanisms. By lowering core body temperature, melatonin reduces arousal and increases sleep-propensity. Thus, in humans, one role of melatonin is to transduce the light-dark cycle and define a window-of-opportunity in which sleep-propensity is enhanced. As such, melatonin is likely to be an effective hypnotic agent for sleep disruption associated with elevated temperature due to low circulating melatonin levels. The combined circadian and hypnotic effects of melatonin suggest a synergistic action in the treatment of sleep disorders related to the inappropriate timing of sleep and wakefulness. Adjuvant melatonin may also improve sleep disruption caused by drugs known to alter normal melatonin production (e.g., beta-blockers and benzodiazepines). If melatonin is to be developed as a successful clinical treatment, differences between the pharmacological profile following exogenous administration and the normal endogenous rhythm should be minimized. Continued development as a useful clinical tool requires control of both the amplitude and duration of the exogenous melatonin pulse. There is a need to develop novel drug delivery systems that can reliably produce a square-wave pulse of melatonin at physiological levels for 8-10 hr duration.
Body Temperature Regulation↗
A randomised controlled trial of psychotherapy in patients with refractory irritable bowel syndrome.
Patients with chronic, refractory irritable bowel syndrome (n = 102) were entered into a randomised controlled trial of psychotherapy versus supportive listening. Independent physical and psychological assessments were carried out at the beginning and end of the 12-week trial. For women, psychotherapy was found to be superior to supportive listening, in terms of an improvement in both physical and psychological symptoms. There was a similar trend for men, but this did not reach significance. Following completion of the trial, patients in the control group were offered psychotherapy; 33 accepted and following treatment experienced a marked improvement in their symptoms; ten declined. At follow-up one year later, those patients who had received psychotherapy remained well, patients who had dropped out of the trial were unwell with severe symptoms, and most of the controls who declined psychotherapy had relapsed. This study shows that psychotherapy is feasible and effective in the majority of irritable bowel syndrome patients with chronic symptoms unresponsive to medical treatment.
Adult↗
Increased cytotoxicity of squamous cell carcinoma of the head and neck by combining cisplatin with VP-16 and ciprofloxacin.
Chemotherapeutic treatment of squamous cell carcinoma (SCC) of the head and neck has been largely ineffective because of tumor cell resistance. This study examined combinations of cisplatin, 4' demethylepipodophyllotoxin ethylidene D-glucoside (VP-16), and ciprofloxacin, a quinolone antibiotic. VP-16 and ciprofloxacin were used in an effort to inhibit DNA repair and increase cytotoxicity. Chemotherapeutic agents often have a direct damaging effect on cellular DNA. Cytotoxicity may be the result of incomplete DNA repair mechanisms; whereas tumor cell resistance to drugs may be due to efficient DNA recovery. A nuclear enzyme especially important to DNA repair and cell growth is topoisomerase II (topo II). Targeted inhibition of topo II by VP-16 and ciprofloxacin may cause increased cisplatin cytotoxicity. SCC cell lines of head and neck origin were treated with a combination of cisplatin, VP-16, and/or ciprofloxacin with cell viability being assessed by the MTT colorimetric assay. Four of five SCC lines examined demonstrated significant augmentation of cisplatin cytotoxicity with the addition of both VP-16 and ciprofloxacin. These in vitro data suggest methods may exist for improving the chemotherapeutic treatment of SCC of the head and neck.
Antineoplastic Combined Chemotherapy Protocols↗
Osteomyelitis due to Mycobacterium haemophilum in a patient with AIDS.
A case of osteomyelitis resulting from infection with Mycobacterium haemophilum in a patient with the Acquired Immunodeficiency Syndrome (AIDS) and Hodgkin's disease is described. The clinical features and response to therapy are examined and compared to previous reported cases. Mycobacterium haemophilum infection in immunocompromised patients usually results in cutaneous lesions but osteomyelitis may be the presenting feature. Tissue samples should be obtained early for microbiological examination and treatment should consist of surgical debridement and appropriate antimicrobial therapy.
Acquired Immunodeficiency Syndrome↗
Phase resetting of the human circadian pacemaker with use of a single pulse of bright light.
Since the initial studies reporting that light can alter the phase position of the human circadian system, there has been increasing interest in the use of bright light as a tool for manipulating the phase position of the circadian pacemaker. Exposure protocols typically require subjects to receive 2-5 h of exposure over several circadian cycles. As a consequence, bright light treatment can involve a considerable time investment. However, recent studies indicate that a single pulse of bright light can produce significant phase shifts in the circadian pacemaker. If a single pulse of bright light can produce significant phase-shifting effects, multiple-pulse designs may be unnecessary. This study examined the phase-shifting effects of a single 4-h pulse of bright light (12,000 lux) in 14 male and one female subject aged between 19-45 years. With use of a "constant routine" to estimate circadian phase, a single 4-h pulse of light produced significant shifts in the phase of the core temperature rhythm. The timing of the exposure, relative to the core temperature rhythm, determined the degree and direction of the phase shift. Exposure immediately prior to habitual bedtime produced a mean phase delay in the core temperature of 2.39 h (SD = 1.37 h). In contrast, exposure immediately following habitual wake-up produced a mean phase advance of 1.49 h (SD = 2.06 h). In addition, the magnitude of the shift increased the closer the light pulse was to the individual's estimated endogenous core temperature minimum. There was, however, considerable interindividual variability in this relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
When the human circadian system is caught napping: evidence for endogenous rhythms close to 24 hours.
It is now well acknowledged that napping constitutes an inherent component of the human circadian system. To date, however, few studies have examined the effects of spontaneous napping on human free-running rhythms. This study investigated the free-running circadian periods of rest/activity and body core temperature in a group of young subjects who were permitted to nap during their time in isolation. Based on the frequency of self-reported sleep bouts, subjects were classified as Nappers or Nonnappers. Nappers exhibited free-running rhythms in both rest/activity and body core temperature that were not significantly different from 24 hours. Nappers showed a tendency for shorter free-running periods in both variables, when compared with Nonnappers. These findings emphasize the need for careful reassessment of data obtained from traditional free-run protocols.
Adult↗
A potential animal model for studying CF heterozygote advantage: genetic variation in theophylline-inducible colonic chloride currents among inbred strains of mice.
We have used Ussing chambers to measure chloride secretion by colonic segments (mucosa, muscularis, and serosa) from various inbred strains of mice. We found lower theophylline-induced Cl- secretion in the DBA/2J than in the C57BL/6J strain. Their F1 showed significantly higher levels of Cl- secretion than did the C57BL/6J parental strain while colonic segments from five recombinant inbred B x D lines ranged between the C57BL/6J and F1 values. No major component of the variation appeared to be associated with alleles of the met oncogene region of chromosome 6 or the H-2 region of chromosome 17.
Animals↗
Meiotic recombination on artificial chromosomes in yeast.
We have examined the meiotic recombination characteristics of artificial chromosomes in Saccharomyces cerevisiae. Our experiments were carried out using minichromosome derivatives of yeast chromosome III and yeast artificial chromosomes composed primarily of bacteriophage lambda DNA. Tetrad analysis revealed that the artificial chromosomes exhibit very low levels of meiotic recombination. However, when a 12.5-kbp fragment from yeast chromosome VIII was inserted into the right arm of the artificial chromosome, recombination within that arm mimicked the recombination characteristics of the fragment in its natural context including the ability of crossovers to ensure meiotic disjunction. Both crossing over and gene conversion (within the ARG4 gene contained within the fragment) were measured in the experiments. Similarly, a 55-kbp region from chromosome III carried on a minichromosome showed crossover behavior indistinguishable from that seen when it is carried on chromosome III. We discuss the notion that, in yeast, meiotic recombination behavior is determined locally by small chromosomal regions that function free of the influence of the chromosome as a whole.
Bacteriophage lambda↗
Aging young sleep: a test of the phase advance hypothesis of sleep disturbance in the elderly.
With aging, the phase relationship between sleep and body core temperature is altered such that the temperature minimum occurs substantially earlier in the major nocturnal sleep period. The sleep maintenance difficulties that often accompany normal aging are generally assumed to be associated with this age-related change in the phase angle between sleep and temperature. To test this notion, we used timed exposure to bright light to reproduce in healthy young adults a similar phase relationship between temperature and sleep, to determine if such a manipulation would induce the same fragmented nocturnal sleep commonly observed in individuals over 65 years of age. Seven young adults were exposed to morning bright light for 3 consecutive days following a baseline night. Bright light exposure caused a 97 min phase advance of the fitted temperature minimum when compared with baseline. Significant declines in several measures of sleep quality were associated with the phase advance, including wakefulness after initial sleep onset (WASO), sleep efficiency and number of stage changes. Yet, the severity of sleep disturbance exhibited by these subjects did not approach that exhibited by most elderly subjects. The findings suggest that while chronophysiological changes appear to be strongly associated with the tendency to awaken in the early morning, they cannot account entirely for the severity of sleep disturbance frequently observed in older subjects.
Journal Article↗
The variability in circadian phase and amplitude estimates derived from sequential constant routines.
Both the constant routine (CR) and the dim light melatonin onset have been suggested as reliable methods to determine circadian phase from a single circadian cycle. However, both techniques lack published studies quantifying the intercycle variability in their phase resolution. To address this question eight healthy male subjects participated in two CRs, 7 days apart. Circadian phase was determined using 3-min samples of core body temperature and two hourly urinary sulphatoxy melatonin excretion rates. Phase and amplitude were estimated using simple (24 h) and complex (24 + 12 h) cosinor models of temperature data and the onset, offset, and a distance-weighted-least-squares (DWLS) fitted acrophase for the melatonin metabolite. The variability in phase estimates was measured using the mean absolute difference between successive CRs. Using the simple 24 h model of temperature data, the mean absolute phase difference was 51 min (SD = 35 min). Using the complex model, the mean absolute phase difference was 62 min (SD = 35 min). Using the DWLS fitted acrophase for the melatonin metabolite, the mean absolute phase difference between CR1 and CR2 was 40 min (SD = 26 min). The results indicate that for CRs a week apart, the mean absolute difference in an individual's phase estimate can vary by 40-60 min depending on the choice of dependent measure and analytic technique. In contrast to the intraindividual variability, the group results showed considerably less variability. The mean algebraic difference between CRs, using temperature- or melatonin-derived estimates, was less than 5 min, and well within the range of normal measurement error.
Adult↗