Plasticity in the haemopoietic system.
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Adaptation, Physiological↗
Biomedical subjects
J H Williams
Publications and source records attributed to J H Williams.
Death in the dental chair.
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Anesthesia, Dental↗
Cholecystokinin infusion and gall bladder dysfunction.
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Cholecystokinin↗
Staging of dietary patterns among African American women.
This article describes the development of a behavioral staging algorithm for use in the Eat Well, Live Well Nutrition Program, a peer-delivered community-based program for African American women (N = 301). The authors examined whether increased frequency in performing low-fat eating behaviors and lower percentage calories from fat intake resulted as a participant moved through five stages of readiness to change each of five low-fat dietary patterns. Frequency of performing low-fat dietary behaviors was significantly different (p<.05) between four stages for the pattern of avoid fried foods, three stages for modify meats, and two stages for the patterns of substitution, avoid fat as seasoning, replacement. Percentage calories from fat were significantly different (p<.05) between four stages for the pattern of replacement, three stages for avoid fried foods and modify meats, and two stages for substitution and avoid fat as seasoning. Implications of these findings for the tailoring of community-based dietary programs are presented.
Adult↗
Functionally distinct groups of interneurons identified during rhythmic carbachol oscillations in hippocampus in vitro.
During distinct behavioral states, the hippocampus exhibits characteristic rhythmic electrical activity. Evidence in vivo suggests that both principal pyramidal cells and GABAergic interneurons participate in generating oscillations. We found that during rhythmic oscillations in area CA3, functionally distinct classes of interneurons could be identified, although all recorded interneurons had similar dendritic and axonal arbors. One group of interneurons was powerfully excited by CA3 pyramidal cells, whereas two other interneuron groups were relatively unaffected by pyramidal cell firing. One of these groups of interneurons was potently inhibited by other local interneurons during the pyramidal cell bursts. Our findings emphasize that morphologically similar cells are wired together very differently within the local circuit. The classes of hippocampal interneurons we have tentatively defined may be used during distinct behavioral states to switch the local network from one oscillatory state to another.
Animals↗
Complex organisation of the 5'-end of the human glycine tRNA synthetase gene.
Glycine tRNA synthetase (glyRS) catalyses the addition of the amino acid glycine to its cognate tRNA molecules. In the silk moth worm Bombyx mori, this gene is subject to complex transcriptional regulation because of the predominance of glycine in silk. In vertebrates, glycine is a major constituent of collagen but there have been no studies of glyRS regulation. In this study we have isolated and mapped a genomic clone containing the 5'-end of glyRS. Primer extension studies identified only one transcriptional start point (TSP) in three different cell lines. Expression of the transcript identified may be regulated translationally because it contains five potential initiation codons, three of which are in good context for initiation. The most 3' of the potential initiation codons has previously been predicted to be the initiating codon for cytoplasmic glyRS. Two of the upstream codons are in-frame with this codon, and both are predicted to extend the N-terminus of glyRS to include a mitochondrial targeting sequence. Sequencing of genomic DNA surrounding the TSP showed features common to the promoters of housekeeping genes, as well as a canonical TATA box at the unusual position of +9. Surprisingly, promoter activity in vitro was not specified by a 1.9 kb genomic fragment containing the TSP and TATA box, but by a contiguous 0.4 kb fragment immediately downstream. These studies suggest that the transcription of glyRS from a single start point requires downstream promoter elements.
Animals↗
High dose intravenous oestrogen (fosfestrol) in the treatment of symptomatic, metastatic, hormone-refractory carcinoma of the prostate.
OBJECTIVE: High dose intravenous stilboestrol has a direct cytotoxic effect on prostatic carcinoma cells. The purpose of this study was to assess subjective and objective responses in a select group of patients with metastatic, hormone-refractory carcinoma of the prostate with severe generalized bone pain in association with symptoms of advanced local disease. PATIENTS AND METHODS: Seventeen patients with metastatic carcinoma of the prostate, who had relapsed following a good initial response to androgen ablation, were treated as inpatients with once daily intravenous injection of 1104 mg diethylstilboestrol diphosphate (Honvan, Asta Medica, Cambridge, UK) for 7 days. The hormone-refractory status was confirmed by castrate serum testosterone levels. All the patients had failed to respond to second-line hormone manipulation and had progressive disease. All the patients had generalized bone pain, 11 also had symptoms of bladder outlet obstruction, 3 had recurrent haematuria and 3 had both. The mean age was 74 years (range 59-83), mean time to chemical relapse (rising PSA) was 29 months (range 1-70), and mean time to clinical relapse was 37 months (range 6-98). The WHO pain score, performance status score, and a patient-specific quality of life (daily living activity) were used as the subjective measures and the serum PSA as an objective marker. All the parameters were recorded before, during and up to three months after treatment. RESULTS: Two patients had a transient relief of bone pain with the pain score reducing by two points. Overall, the pain and performance scores and the local symptoms did not improve. The PSA level continued to rise in all patients. Despite parenteral pre-medication with pethidine and cyclizine, all the patients suffered nausea and pain following the injection. One patient died on the fifth day of treatment from a myocardial infarction and 4 developed deep vein thrombosis. All the patients required further symptom control measures. CONCLUSION: High dose intravenous stilboestrol causes considerable morbidity without any objective or subjective response in the treatment of patients with symptomatic, hormone-refractory metastatic carcinoma of the prostate.
Aged↗
Changes in skeletal muscle sarcoplasmic reticulum function and force production following myocardial infarction in rats.
In patients following myocardial infarction (MI), exercise tolerance and muscular strength are often markedly reduced. The purpose of this investigation was to determine if calcium (Ca2+) uptake and release by skeletal muscle sarcoplasmic reticulum (SR) are altered following MI and if such changes are associated with diminished muscular performance. SR vesicles were isolated from rat gastrocnemius muscle at 6 and 12 weeks following MI (via left coronary artery ligation) or sham surgery. At both post-surgery intervals, the rates of Ca2+ uptake (measured using fura-2) were 35% greater in the MI group. In addition, the rates of Ca2+ release were increased in the MI group by 10 and 30% at 6 and 12 weeks, respectively. At 12 weeks post-surgery, animals of the MI group showed significant reduction in in situ twitch and tetanic forces and significant elevations in the rates of tension increase and decrease. These data indicate that SR Ca2+ exchange is altered following MI. In addition, changes in SR function are associated with changes in force production by the whole muscle.
Adenosine Triphosphate↗
Glucose 6-phosphate alters rat skeletal muscle contractile apparatus and sarcoplasmic reticulum function.
We investigated the effects of glucose 6-phosphate (G6P) on skeletal muscle contractile apparatus and sarcoplasmic reticulum (SR) function. Using rat extensor digitorum longus fibres, the presence of 5 mM G6P decreased the Ca2+ sensitivity of both force production and actomyosin ATPase (AM-ATPase) activity. Conversely, maximal Ca(2+)-activated force was unaffected while maximal AM-ATPase activity was increased by 37%. In SR vesicles isolated from rat gastrocnemius, G6P markedly altered Ca2+ handling. It increased Ca(2+)-stimulated Ca(2+)-ATPase activity but depressed the net rate of Ca2+ uptake. This latter effect appears to be due to G6P-stimulated Ca2+ release. When G6P was added to Ca(2+)-loaded vesicles, a small, transient release of Ca2+ was elicited. In addition, G6P lowered the threshold for Ca(2+)-induced Ca2+ release but depressed the net rates of both AgNO3- and caffeine-induced releases. It is possible that the accumulation of G6P during muscular activity may adversely affect muscle force production and contribute to the fatigue process via its action on the contractile apparatus and SR.
Animals↗
Effects of lactate on force production by mouse EDL muscle: implications for the development of fatigue.
Numerous studies suggest that the accumulation of lactate during exercise contributes to the fatigue process. This notion is based on close negative correlations between force and intracellular muscle lactate concentrations during fatigue and recovery. In this investigation, we attempted to determine if lactate directly affects muscle force output. This was accomplished by incubating mouse extensor digitorum longus muscles in extracellular concentrations of 10, 20, 30 and 50 mM L-(+)-lactate at 21 and 37 degrees C and monitoring force output. At 21 degrees C, 30 and 50 mM, extracellular lactate significantly reduced tetanic force (Po 250 ms, 100 Hz) to 95 and 93% of initial, respectively. In addition, the rate of force development (+dP/dt) was reduced to 93 and 89% of initial. At 37 degrees C, the effects of extracellular lactate were augmented as Po was reduced to 73 and 62% of initial and +dP/dt was reduced to 55 and 44% of initial at 30 and 50 mM, respectively. We next sought to determine if the reduction in Po was due to altered sarcoplasmic reticulum (SR) function using a muscle homogenate fraction. The rate of AgNO3-induced SR Ca2+ release was depressed by 31% in the presence of 25 mM lactate. These results suggest that elevated lactate depresses force production by whole muscle and may play some role in the fatigue process. In addition, it appears that lactate depresses force production, in part, by inhibiting Ca2+ release from the SR.
Animals↗
Effects of varied fatigue protocols on sarcoplasmic reticulum calcium uptake and release rates.
The purpose of this investigation was to examine changes in sarcoplasmic reticulum (SR) function in muscles subjected to different patterns of muscle activity. Frog sartorius muscles were stimulated with tetanic trains (100 ms, 100 Hz) delivered at rates of 2.0, 0.5, and 0.2 trains/s. In one set of experiments, stimulation was continued until force had declined to approximately 17% of initial (constant fatigue), whereas in the other set, stimulation was continued for 1 min (constant duration). In the constant-fatigue experiments, Ca2+ uptake (1 mM MgATP) and release rates (25 microM AgNO3, 5 mM 4-chloro-m-cresol) were depressed by similar extents following each protocol. This occurred despite 1, 4, and 17 min of stimulation, respectively, used to induce fatigue. In the constant-duration experiments, larger reductions in SR function occurred following the highest frequency stimulation protocol. These data suggest that when muscles are fatigued to similar extents, depressions in SR function are independent of the activity protocol. On the other hand, when a constant duration of activity is imposed, changes in SR function are closely linked to the extent of force reduction.
Adenosine Triphosphate↗
E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions.
The objectives of this research were to determine the contribution of excitation-contraction (E-C) coupling failure to the decrement in maximal isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles after eccentric contractions and to elucidate possible mechanisms. The left anterior crural muscles of female ICR mice (n = 164) were injured in vivo with 150 eccentric contractions. Po, caffeine-, 4-chloro-m-cresol-, and K+-induced contracture forces, sarcoplasmic reticulum (SR) Ca2+ release and uptake rates, and intracellular Ca2+ concentration ([Ca2+]i) were then measured in vitro in injured and contralateral control EDL muscles at various times after injury up to 14 days. On the basis of the disproportional reduction in Po (approximately 51%) compared with caffeine-induced force (approximately 11-21%), we estimate that E-C coupling failure can explain 57-75% of the Po decrement from 0 to 5 days postinjury. Comparable reductions in Po and K+-induced force (51%), and minor reductions (0-6%) in the maximal SR Ca2+ release rate, suggest that the E-C coupling defect site is located at the t tubule-SR interface immediately after injury. Confocal laser scanning microscopy indicated that resting [Ca2+]i was elevated and peak tetanic [Ca2+]i was reduced, whereas peak 4-chloro-m-cresol-induced [Ca2+]i was unchanged immediately after injury. By 3 days postinjury, 4-chloro-m-cresol-induced [Ca2+]i became depressed, probably because of decreased SR Ca2+ release and uptake rates (17-31%). These data indicate that the decrease in Po during the first several days after injury primarily stems from a failure in the E-C coupling process.
Animals↗
Functional aspects of skeletal muscle contractile apparatus and sarcoplasmic reticulum after fatigue.
This study examined the effects of fatigue on the functional aspects of the contractile apparatus and sarcoplasmic reticulum (SR). Frog semitendinosus muscles were stimulated to fatigue, and skinned fibers or a homogenate fraction was prepared from both fatigued and rested contralateral muscles. In fatigued fibers, maximal Ca2+-activated force of the contractile apparatus was unaltered, whereas maximal actomyosin-ATPase activity was depressed by 20%. The Ca2+ sensitivity of force was increased, whereas that of actomyosin-ATPase was not altered. Also, the rate constant for tension redevelopment was decreased at submaximal Ca2+ concentration. These latter findings suggest that fatigue slows the dissociation of force-generating myosin cross bridges. Ca2+ uptake and Ca2+-ATPase activity of the SR were depressed by 46 and 21%, respectively, in the fatigued muscles. Fatigue also reduced the rates of SR Ca2+ release evoked by AgNO3 and 4-chloro-m-cresol by 38 and 45%, respectively. During fatigue, the contractile apparatus and SR undergo intrinsic functional alterations. These changes likely result in altered force production and energy consumption by the intact muscle.
Animals↗
Reduced latent inhibition in people with schizophrenia: an effect of psychosis or of its treatment.
BACKGROUND: People with schizophrenia show impaired attention. This could result from reduced latent inhibition (a measure of ability to filter out irrelevant stimuli). Previous studies have found reduced auditory latent inhibition in people with acute schizophrenia: we tested whether this results from psychosis or from drug treatment. METHOD: We measured auditory latent inhibition in two studies. One compared antipsychotic-naive people with acute schizophrenia with patients within two weeks of starting antipsychotic treatment. The second compared healthy volunteers given either saline or 1.0 mg haloperidol, intravenously. RESULTS: Latent inhibition was absent in treated patients, but was clearly present in patients who were naive to antipsychotics. Latent inhibition was absent in volunteers given haloperidol, but was clearly present in those given saline. CONCLUSIONS: The reduced auditory latent inhibition seen in acute schizophrenia is more plausibly due to antipsychotic treatment than to the disorder. Unless neuropsychological models of schizophrenia incorporate evidence from drug-free patients and drug-treated healthy controls, they may be invalid.
Adult↗
Using behavioural ecology to understand depression.
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Adaptation, Psychological↗
Sarcoplasmic reticulum responses to repeated sprints are affected by conditioning of horses.
Sarcoplasmic reticulum (SR) responses to repeated sprints and to physical conditioning were studied in 10 Quarter Horses. Exercise tests (four repeated sprints on a treadmill) were conducted before and after 12 wk of sprint conditioning. Muscle samples from the middle gluteal muscle were taken before and after each exercise test, and SR vesicles were isolated. Calcium uptake was determined spectrophotometrically using antipyrylazo III, and Ca2+-ATPase activity was determined using an enzyme-linked optical assay. Conditioning increased calcium uptake rate and Ca2+-ATPase activity by 14 and 38%, respectively, before exercise and by 25 and 26% after exercise. Exercise decreased calcium uptake rate and Ca2+-ATPase activity by 37 and 27%, respectively, before conditioning and by 28 and 21% after conditioning. Decreases in calcium uptake and Ca2+-ATPase activity of SR have been associated with fatigue during exercise, and this association is strengthened by the moderating effect of conditioning.
Animals↗
The role of colour Doppler imaging in the management of Peyronie's disease.
OBJECTIVE: To determine the role of colour Doppler imaging (CDI) in the investigation of erectile dysfunction in patients with Peyronie's disease. PATIENTS AND METHODS: Fifty consecutive patients (age 35-75 years) with Peyronie's disease who were considered suitable for surgical treatment were investigated using CDI to determine the haemodynamic variables of penile vasculature after an intracorporeal injection of 20 microg of alprostadil (with manual self-stimulation). A clinician independently recorded the quality of erection and the deformity. RESULTS: Twenty of 50 patients (40%) considered they had normal erectile function despite their penile deformity and all had normal responses, although they tended to exaggerate the degree of penile deformity. Of the 30 remaining patients, 21 who considered themselves to have erectile dysfunction had normal clinical and CDI haemodynamic responses to alprostadil. The remaining nine patients had a variety of erectile problems and whilst CDI showed altered haemodynamic values, in no case did CDI alter the proposed treatment based on the clinically apparent features of those patients. CONCLUSION: Colour Doppler imaging of the penis after pharmacologically induced erection gives anatomical and functional information in patients with Peyronie's disease but does not provide useful additional information to aid the selection of surgical treatment for the disease.
Adult↗
Strategies for recruitment to a population-based lung cancer prevention trial: the CARET experience with heavy smokers. Beta-Carotene and Retinol Efficacy Trial.
The Beta-Carotene and Retinol Efficacy Trial tested the effect of the combination of beta-carotene (30 mg) and retinyl palmitate (25,000 units) daily on the incidence of lung cancer in high-risk individuals. In study centers located in Seattle, WA; Portland, OR; and Irvine, CA, we recruited current and recent ex-cigarette smokers, aged 50-69 years. Our primary method of recruitment was by mailing study information and eligibility questionnaires to age-selected health insurance subscribers. A total of 1,216,549 subscriber households were contacted, which resulted in 16,449 enrollments and 12,184 randomizations. Other methods of recruitment yielded 1421 enrollments and 1002 randomizations. Seventy-four % of those participants who enrolled in the 3-month placebo run-in were randomized. The major reasons for nonrandomization once subjects were enrolled were: becoming ineligible (13%), concern about or development of side effects attributed to the study vitamins (18%), loss of interest or being too busy (23%), and not showing up at the appointed time or not willing to come to the study center (23%). Here, we discuss the reasons for nonparticipation and for subjects leaving the trial prior to randomization and possible modifications of trial design and procedures to address these problems. This recruitment approach provided a constant flow of potentially eligible participants, screened out many ineligible and uninterested persons prior to the scheduling of a study center visit, and ensured randomization of committed participants. A major limitation of this study was that the pool of minorities that was reached was small.
Aged↗