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Biomedical subjects

C J Clark

Publications and source records attributed to C J Clark.

At least 19 recordsLinked to original sources
PubMed2003

Analysis of the 5' flanking region of the interleukin 10 gene in patients with systemic sclerosis.

OBJECTIVES: Fibrosis, a feature of systemic sclerosis (SSc), is more severe in the diffuse compared with the limited disease variant. Interleukin 10 (IL-10) is an anti-inflammatory cytokine which reduces type 1 collagen mRNA levels in human fibroblasts. The 5' flanking region of the IL-10 gene is highly polymorphic, with three single base pair substitutions at position -1082(G/A), -819(C/T) and -592(C/A), which results in differential IL-10 production. The GCC/GCC genotype is associated with high IL-10 production while the ATA/ATA genotype with low production. We postulated that there would be a difference in IL-10 polymorphisms in patients with limited (lSSc) and diffuse (dSSc) disease. METHODS: Patients with limited (lSSc, n = 89) or diffuse (dSSc, n = 51) disease plus controls (n = 94) were recruited. DNA was isolated from peripheral blood and polymorphisms analysed using amplification refractory mutation system (ARMS) polymerase chain reaction (PCR). RESULTS: dSSc patients were less likely to carry the genotype indicative of high IL-10 production when compared with controls (controls vs dSSc; 29 vs 4%, chi2 = 15.7, 5 df, P = 0.005) and lSSc patients (lSSc vs dSSc; 21 vs 4%, chi2 = 17.5, 5 df, P = 0.002). There was no difference between control and lSSc patients. While there was no difference between controls and lSSc haplotypes, the GCC haplotype distribution did differ significantly between controls and dSSc patients (controls vs dSSc; 54 vs 36%, chi2 = 11.2, 2 df, P = 0.001). A significant difference was also observed between lSSc and dSSc haplotype distribution (lSSc vs dSSc; 48 vs 36%, chi2 = 13.5, 2 df, P < 0.001). CONCLUSION: We demonstrate that IL-10 genotypes associated with high IL-10 production are under-represented in dSSc. This may have implications in the disease pathology.

DNA↗
PubMed2002

Analysis of transforming growth factor beta1 gene polymorphisms in patients with systemic sclerosis.

OBJECTIVES: To determine the distribution of transforming growth factor beta1 (TGFbeta1) genotypes at codon 10 (+869 polymorphism) and codon 25 (+915 polymorphism) in patients with scleroderma (SSc). Differences between diffuse and limited SSc (dSSc and lSSc) were also investigated. METHODS: Patients with lSSc (n=89) and dSSc (n=63) were compared with 147 controls. DNA was isolated from peripheral blood and polymorphisms at codons 10 (C/T) and 25 (G/C) of the TGFbeta1 gene analysed by polymerase chain reaction and sequence specific oligonucleotide probing. RESULTS: Significantly more patients with SSc than controls carried allele C at codon 10 (controls v SSc, 38% v 48%, chi(2)=8.2, 1df, p=0.004), OR=1.95 (95% CI 1.16 to 3.27). The difference remained when patients with SSc were split into those with limited or diffuse disease, (controls v dSSc, chi(2)=5, 1df, p=0.02 and controls v lSSc, chi(2)=6, 1df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls v SSc, chi(2)=45, 1df, p<0.0001). Possession of allele C at codon 10 gave an OR=4.8 (95% CI 2.8 to 8.4). No difference in allele frequency was seen between patients with SSc and controls at codon 25. More patients with SSc than controls carried the GG genotype (controls v SSc, 80% v 88%, chi(2)=7, 2df, p=0.027). Possession of allele G gave an OR=1.7 (95% CI 0.5 to 5.9). There was no difference between diffuse and limited disease at either codon. CONCLUSIONS: These results suggest that patients with SSc are genetically predisposed to high TGFbeta1 production. These polymorphisms do not, however, explain the difference in the clinical phenotypes of limited and diffuse SSc.

Codon↗
PubMed2002

Home based neuromuscular electrical stimulation as a new rehabilitative strategy for severely disabled patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Passive training of specific locomotor muscle groups by means of neuromuscular electrical stimulation (NMES) might be better tolerated than whole body exercise in patients with severe chronic obstructive pulmonary disease (COPD). It was hypothesised that this novel strategy would be particularly effective in improving functional impairment and the consequent disability which characterises patients with end stage COPD. METHODS: Fifteen patients with advanced COPD (nine men) were randomly assigned to either a home based 6 week quadriceps femoris NMES training programme (group 1, n=9, FEV(1)=38.0 (9.6)% of predicted) or a 6 week control period before receiving NMES (group 2, n=6, FEV(1)=39.5 (13.3)% of predicted). Knee extensor strength and endurance, whole body exercise capacity, and health related quality of life (Chronic Respiratory Disease Questionnaire, CRDQ) were assessed. RESULTS: All patients were able to complete the NMES training programme successfully, even in the presence of exacerbations (n=4). Training was associated with significant improvements in muscle function, maximal and endurance exercise tolerance, and the dyspnoea domain of the CRDQ (p<0.05). Improvements in muscle performance and exercise capacity after NMES correlated well with a reduction in perception of leg effort corrected for exercise intensity (p<0.01). CONCLUSIONS: For severely disabled COPD patients with incapacitating dyspnoea, short term electrical stimulation of selected lower limb muscles involved in ambulation can improve muscle strength and endurance, whole body exercise tolerance, and breathlessness during activities of daily living.

Aged↗
PubMed2002

11beta-hydroxylase and aldosterone synthase expression in fetal rat hippocampal neurons.

The central nervous system produces many of the enzymes responsible for corticosteroid synthesis. A model system to study the regulation of this local system would be valuable. Previously, we have shown that primary cultures of hippocampal neurons isolated from the fetal rat can perform the biochemical reactions associated with the enzymes 11beta-hydroxylase and aldosterone synthase. Here, we demonstrate directly that these enzymes are present within primary cultures of fetal rat hippocampal neurons.

Adrenal Glands↗
PubMed2001

Seasonal variation in the feeding ecology of the grey-cheeked mangabey (Lophocebus albigena) in Cameroon.

Seasonal fluctuations in resource abundance often cause primates to change their feeding behavior and ecology. The objective of this study was to examine the response of a largely frugivorous monkey, the grey-cheeked mangabey (Lophocebus albigena), to seasonal variations in fruit abundance. We used 15-min scan sampling to quantify feeding, activity, and habitat use by monkeys between February and December 1998 in the Dja Reserve, Cameroon. L. albigena were found to have omnivorous feeding habits, consuming the fruits, seeds, leaves, and flowers of 132 plant species. Although monkeys fed from many plant species, only five plant species accounted for 45% of all feeding records. The number of feeding observations on a plant species was significantly correlated with its fruit production. L. albigena responded to fruit-lean periods by shifting from a diet dominated by fruit to one dominated by seeds, flowers, and young leaves. This diet shift coincided with greater use of swamp habitat and higher dietary diversity. L. albigena spent the greatest percentage of scan samples feeding and traveling, but activities varied significantly over the day. Individuals spent a significantly higher percentage of scan samples feeding during the fruit-rich season than in the fruit-lean season. Comparing our results to those of studies in Gabon and Uganda, we found that L. albigena differ across regions in the number of plant species they consume and time spent feeding. These differences may be a result of variations in tree diversity or the strength of seasonal fluctuations in resource abundance among sites.

Animals↗
PubMed2001

Management of lymphoma patients in a cancer unit: an audit of 15 years' experience in a district general hospital.

The objectives were to analyse data obtained in a district general hospital medical oncology unit over a 15-year period, and to provide a comparator for standards of care for lymphoma patients in new cancer units. Prospectively collected data were analysed on 208 consecutive patients presenting with lymphoma, on an 'all-comers' basis, between 1981 and 1996. Treatment was with radiotherapy and/or chemotherapy, according to local protocols. The outcome measure was survival from the date of diagnosis. The 5-year actuarial survival was 72.7% for Hodgkin's disease and 55.7% for non-Hodgkin's lymphoma. Age and stage of disease were the only predictors of survival in a multivariate analysis. Histological classification was not a useful predictor of survival in this analysis. Survival figures comparable with those obtained nationally and across Europe are attainable in a cancer unit. Multiple pathways of referral of lymphoma patients operate in our region.

Adolescent↗
PubMed2000

Using (1)H magnetic resonance imaging and complementary analytical techniques to characterize developmental changes in the Zantedeschia Spreng. tuber.

Nuclear magnetic resonance imaging (MRI) and complementary analytical techniques were used to examine tissue structure and developmental changes occurring during active growth in the root tuber of ZANTEDESCHIA: Spreng. cv. Chianti, a commercially significant cut flower. Plants were observed during the period of leaf senescence and tuberization at the end of the first growth cycle of micropropagated plantlets and, following cool storage to break endodormancy, during development occurring after the replanting of ecodormant tubers. MRI distinguished two distinct regions within the tuber, and the differences in the binding state of water in the two regions were reflected in differences in tissue morphology and function. An abundance of free water was observed in tissue comprised of large parenchyma cells, at the base of the tuber. This tissue appeared to be involved in maintaining the viability of the plant during the period of dormancy, a function indicated primarily by increased metabolic activity in this tissue during dormancy, and reduced metabolic activity during periods of active growth. In contrast, water was more tightly bound in tissue comprised of small parenchyma cells. This tissue appeared to operate as a region for dynamic carbohydrate storage. The initial increase in the free water content of this tissue during the growth phase was linked to the mobilization of starch during canopy development. The subsequent decrease in free water in the remainder of the growth period was linked to the reaccumulation of starch while the tuber functioned as a sink for photosynthate prior to canopy senescence.

Carbohydrate Metabolism↗
PubMed2000

alpha-adducin and angiotensin I-converting enzyme polymorphisms in essential hypertension.

This study focused on two genes that have previously been implicated in hypertension and may influence renal sodium handling, adducin, and angiotensin I-converting enzyme (ACE). We compared their polymorphic frequencies and interaction in patients with essential hypertension (n=128) and individually age- and gender-matched normotensive control subjects. The alpha-adducin G460W polymorphism was genotyped by DNA amplification and restriction digestion. The ACE I/D polymorphism was assayed by a triple-primer method, with a "nested" polymerase chain reaction primer situated completely within the insertion sequence of the I: allele. The distributions of genotypes and alleles for the two polymorphisms were not significantly different between the case and control populations, and the cross-classification of cases by alpha-adducin and ACE genotype gave a distribution similar to that of control subjects. We have previously reported that the distributions of genotypes for two linked polymorphisms in the aldosterone synthase gene (one in the steroidogenic factor-1 [SF-1] binding site and the other an intronic conversion [IC]) were significantly different between this cohort of essential hypertensives and matched control subjects. The cross-classification of cases by alpha-adducin and SF-1, alpha-adducin and IC, ACE and SF-1, and ACE and IC genotype gave a distribution similar to that of control subjects. Hence, no evidence was found to suggest an association between either the alpha-adducin G460W or the ACE I/D polymorphism and hypertension in a careful case-control study. Furthermore, the alpha-adducin G460W, ACE I/D, and aldosterone synthase SF-1 and IC polymorphisms do not appear to interact in our hypertensive population.

Calmodulin-Binding Proteins↗
PubMed2000

Skeletal muscle strength and endurance in patients with mild COPD and the effects of weight training.

This study poses two questions: 1) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease (COPD)? and 2) what is the effect of a randomized, controlled, 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients (age 49+/-11 yrs), mean forced expiratory volume in one second (FEV1) 77+/-23% pred and 52 healthy, sedentary subjects (age 51 (10) yrs), mean FEV1 109+/-16% pred. The 43 COPD patients were randomly allocated into training (n=26) and control (n=17) groups. Isokinetic and isotonic muscle function, whole body endurance, maximal exercise capacity and lung function were measured. The COPD patients had reduced isokinetic muscle function (with the exception of sustained upper limb strength) as compared with healthy sedentary subjects. Muscle function improved after weight training in the COPD patients. Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption. A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which cannot be explained by factors such as hypoxaemia and malnutrition. Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning.

Adult↗
PubMed2000

Expression of 11beta-hydroxylase and aldosterone synthase genes in the rat brain.

The terminal stages of cortisol and aldosterone production in the human adrenal gland are catalysed by the enzymes 11beta-hydroxylase and aldosterone synthase, which are encoded by the CYP11B1 and CYP11B2 genes respectively. Recent studies have suggested that aldosterone and cortisol are also made in other tissues such as the brain, heart and vascular system and may play a role in cardiovascular homeostasis. The aim of this study was to confirm the presence of these enzymes and localise them precisely in the rat brain. Reverse transcription-polymerase chain reaction (RT-PCR)/Southern blotting confirmed transcription of CYP11B1 and CYP11B2 in whole brain and hypothalamus minces from Wistar-Kyoto rats. 11beta-Hydroxylase and aldosterone synthase were immunolocalised in paraffin-embedded rat adrenal and brain sections using mouse monoclonal antibodies. Negative controls utilised a mouse monoclonal antibody raised against a non-mammalian epitope. In the brain, 11beta-hydroxylase and aldosterone synthase were detected in the cerebellum, especially the Purkinje cells, as well as the hippocampus. The specificities of the 11beta-hydroxylase and aldosterone synthase antibodies were confirmed by positive immunostaining of the relevant regions of the adrenal cortex. This is the first direct evidence that steroid hydroxylases involved in the final stages of corticosteroid biosynthesis are present in specific regions of the central nervous system.

Animals↗
PubMed2000

Corticosteroid production by fetal rat hippocampal neurons.

11beta-hydroxylase and aldosterone synthase catalyse the final stages of corticosterone and aldosterone synthesis respectively. Previously, we established that they are expressed in the rat brain, particularly the cerebellum and the hippocampus. Primary cultures of fetal rat neurons were studied. RT-PCR and immunohistochemistry established that neurons express 11beta-hydroxylase and aldosterone synthase mRNAs and protein. After incubating the cells with 10microM DOC for 24 hours, medium was analysed for aldosterone and corticosterone. Median % conversion of DOC to corticosterone was 7.6% compared to 0.4% in controls. Median % conversion of DOC to aldosterone was 6.2% compared to 0.06% in controls. Corticosteroids mediate a number of functions of mammalian brain, including blood pressure homeostasis, salt appetite and neuronal excitability. Local production of these steroids could have significant effects on these processes.

Aldosterone↗
PubMed1999

Article I: Prevention and education regarding rabies in human beings. National Working Group on Rabies Prevention and Control.

Substantial changes in the epizootic characteristics of rabies have transpired in the United States during the past 50 years. Traditional veterinary practices and public health recommendations have effectively controlled rabies in dogs and prevented associated human fatalities; however, they have been unable to adequately address the problem of rabies in wildlife. Attributable in part to a renewed focus on emerging infectious diseases, a conference was held at the Centers for Disease Control and Prevention in 1993 to begin discussion focused on the reemergence of rabies and to formulate new suggestions for prevention and control of rabies in the United States. Three major working groups were formed from a national committee of professionals representing a broad array of biomedical disciplines. These groups concentrated on prevention of rabies in human beings, education, laboratory diagnosis of rabies, and rabies control in animals. The groups described the perceived minimum requirements to promote prevention and control of rabies in the United States into the next century. The following article describes the needs and recommendations identified by the prevention and education working group. Two other articles, scheduled for the Nov 15 and Dec 1, 1999 issues of JAVMA, will relay the needs and recommendations of the working groups on laboratory diagnosis of rabies and rabies in wildlife.

Animals↗
PubMed1999

Physical activity and asthma.

The relationship between asthma and exercise and the resultant disability (ie, the impact on activities of daily living, including physical activity) shows wide interpatient and intrapatient variability, being influenced not only by the disease but additional psychosocial variables. There are a variety of helpful pharmacologic and nonpharmacologic measures in dealing with simple exercise-induced asthma, and new therapeutic options are being developed. The cardiorespiratory performance characteristics of asthmatic patients are very frequently suboptimal, either because of symptom-limited exercise tolerance or secondary deconditioning consequent upon inactivity. Medically supervised physical training can produce significant beneficial change. Recommendations for rehabilitation of asthmatic patients would include individualized exercise prescription and advice based on objective criteria of exercise capability, with flexibility in the programs offered, in order to cater to the broadest spectrum of patient disability.

Activities of Daily Living↗
PubMed1996

Sump bay fever: inhalational fever associated with a biologically contaminated water aerosol.

OBJECTIVE: To investigate the clinical, serological, and environmental features of a work related inhalational fever associated with exposure to an aerosol generated from a biologically contaminated 130,000 gallon water pool in a building used for testing scientific equipment. METHOD: Cross sectional survey of all exposed subjects (n = 83) by symptom questionnaire, clinical examination, spirometry, and serology for antibody to Pseudomonads, pool water extract, and endotoxin. In symptomatic patients diffusion capacity was measured, and chest radiology was performed if this was abnormal. Serial peak flow was recorded in those subjects with wheeze. Bacterial and fungal air sampling was performed before and during operation of the water pool pump mechanism. Endotoxin was measured in the trapped waters and in the pumps. Serum cotinine was measured as an objective indicator of smoking. RESULTS: Of the 20 symptomatic subjects, fever was most common in those with the highest exposure (chi 2 42.7, P < 0.001) in the sump bay when the water was (torrentially) recirculated by the water pumps. Symptoms occurred late in the working day only on days when the water pumps were used, and were independent of the serum cotinine. Pulmonary function was normal in most subjects (spirometry was normal in 79/83, diffusion capacity was low in five subjects, chest radiology was normal). Peak flow recording did not suggest a work relation. The bacterial content of the aerosol rose from 6 to > 10,000 colony forming units per cubic metre (cfu/m3) (predominantly environmental Pseudomonads) when the pumps were operating. High endotoxin concentrations were measured in the waters and oil sumps in the pumps. Low concentrations of antibody to the organisms isolated were detected (apart from two subjects with high antibody) but there was no relation to exposure or the presence of symptoms and similar antibody was found in the serum samples from a non-exposed population. The fever symptoms settled completely with the simple expedient of changing the water and cleaning the pumps. CONCLUSION: Given the results of our study, the development of inhalational fever in this unique environment and clearly restricted cohort was closely related to the degree of exposure to contaminated aerosol and mainly occurred in the absence of distinct serological abnormality and independent of cigarette smoking.

Adult↗
PubMed1996

Low intensity peripheral muscle conditioning improves exercise tolerance and breathlessness in COPD.

This randomized, controlled study investigated the physiological effects of a specially designed 12 week programme of isolated conditioning of peripheral skeletal muscle groups. The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital. Forty eight patients, aged 40-72 yrs with chronic obstructive pulmonary disease (COPD) (mean (SD) forced expiratory volume in one second (FEV1) 61 (27)% of predicted normal) were randomly allocated into training (n = 32) and control (n = 16) groups. Physiological assessments were performed before and after the 12 week study period, and included peripheral muscle endurance and strength, whole body endurance, maximal exercise capacity (maximum oxygen consumption (V'O2,max)) and lung function. The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance, with no additional breathlessness. Whole body endurance measured by free arm treadmill walking increased by 6,372 (3,932-8,812) 3 (p < 0.001). Symptom-limited maximal V'O2 was unchanged. However, the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide, both at peak exercise and at equivalent work rate (Wmax). In summary, low intensity isolated peripheral muscle conditioning is well-tolerated, simple and easy to perform at home. The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning.

Exercise↗
PubMed1995

Efficiency of sampling: birthweight and gestational age distributions in two cohorts, < 31 weeks and 500-1499 grams.

We studied the efficiency of two common sampling strategies used to assemble cohorts to study the long-term problems of preterm infants: infants with birthweights of 500-1499 g, and infants with gestational ages (GA) of < 31 weeks. Birthweight, GA and 2-year outcome data from a population based study of infants < 2001 g, the Central New Jersey Brain Hemorrhage Study (NBH), were used to define the birthweight and GA distributions, at enrollment and at the age of 2 years, of overlapping subsets: infants 500-1499 g (n = 599) and infants < 31 weeks of age (n = 522). Using frequencies from the NBH study, we estimated that 1000 infants of 500-1499 g enrolled at birth would produce 712 infants at the age of 2 years, 498 below 31 weeks and 214 above. Enrolling 1000 infants < 31 weeks would produce a cohort of 697 infants at the age of 2, all of whom were < 31 weeks. Neither sampling strategy maximised the statistical power to investigate the pathophysiological determinants of long-term outcomes associated with short GA. Both methods oversampled older GAs. A stratified sampling technique based on GA, designed to produce equal numbers of subjects at each week of GA, would improve statistical power to study long-term outcomes. As we move from descriptive to analytical studies of preterm infants, we need to devise efficient, GA-based, sampling strategies that maximise statistical power to test pathophysiological hypotheses.

Birth Weight↗