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Biomedical subjects

D Ball

Publications and source records attributed to D Ball.

At least 55 records · Page 3Linked to original sources
PubMed2000

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population.

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.

Adult↗
PubMed2000

Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat.

Prolonged treatment with the beta(2)-adrenoceptor agonist clenbuterol (1-2 mg. kg body mass(-1). day (-1)) is known to induce the hypertrophy of fast-contracting fibers and the conversion of slow- to fast-contracting fibers. We investigated the effects of administering a lower dose of clenbuterol (250 microgram. kg body mass(-1). day (-1)) on skeletal muscle myosin heavy chain (MyHC) protein isoform content and adenine nucleotide (ATP, ADP, and AMP) concentrations. Male Wistar rats were administered clenbuterol (n = 8) or saline (n = 6) subcutaneously for 8 wk, after which the extensor digitorum longus (EDL) and soleus muscles were removed. We demonstrated an increase of type IIa MyHC protein content in the soleus from approximately 0.5% in controls to approximately 18% after clenbuterol treatment (P < 0.05), which was accompanied by an increase in the total adenine nucleotide pool (TAN; approximately 19%, P < 0.05) and energy charge [E-C = (ATP + 0.5 ADP)/(ATP + ADP + AMP); approximately 4%; P < 0.05]. In the EDL, a reduction in the content of the less prevalent type I MyHC protein from approximately 3% in controls to 0% after clenbuterol treatment (P < 0.05) occurred without any alterations in TAN and E-C. These findings demonstrate that the phenotypic changes previously observed in slow muscle after clenbuterol administration at 1-2 mg. kg body mass(-1). day(-1) are also observed at a substantially lower dose and are paralleled by concomitant changes in cellular energy metabolism.

Adenosine Diphosphate↗
PubMed2000

Total power output generated during dynamic knee extensor exercise at different contraction frequencies.

A novel approach has been developed for the quantification of total mechanical power output produced by an isolated, well-defined muscle group during dynamic exercise in humans at different contraction frequencies. The calculation of total power output comprises the external power delivered to the ergometer (i.e., the external power output setting of the ergometer) and the "internal" power generated to overcome inertial and gravitational forces related to movement of the lower limb. Total power output was determined at contraction frequencies of 60 and 100 rpm. At 60 rpm, the internal power was 18+/- 1 W (range: 16-19 W) at external power outputs that ranged between 0 and 50 W. This was less (P<0.05) than the internal power of 33+/-2 W (27-38 W) at 100 rpm at 0-50 W. Moreover, at 100 rpm, internal power was lower (P<0.05) at the higher external power outputs. Pulmonary oxygen uptake was observed to be greater (P<0.05) at 100 than at 60 rpm at comparable total power outputs, suggesting that mechanical efficiency is lower at 100 rpm. Thus a method was developed that allowed accurate determination of the total power output during exercise generated by an isolated muscle group at different contraction frequencies.

Adult↗
PubMed2000

GENESiS: creating a composite index of the vulnerability to anxiety and depression in a community-based sample of siblings.

There is considerable evidence for a unitary and dimensional view of the genetic vulnerability to symptoms of anxiety and depression. The GENESiS (Genetic Environmental-Nature of Emotional States in Siblings) Study aims to use a multivariate approach to detect genetic loci that contribute to individual differences in this vulnerability dimension. The study used the UK General Practice Research Framework to generate a community-based sample of siblings. Questionnaire measures of anxiety/depression included the short form of the neuroticism scale from the revised Eysenck Personality Questionnaire (EPQ-N), the General Health Questionnaire (GHQ-12), and the anxious arousal and high positive affect subscales from the Mood and Anxiety Symptoms Questionnaire (MASQ-AA and MASQ-HPA). Genetic model-fitting of 2658 unselected sibships provided evidence for a single common genetic (familial) factor that accounted for a substantial proportion of the genetic variances and covariances of these four measures. Using the parameter estimates of this model, we constructed a composite index of this common genetic factor. This index, which has a sib correlation of 0.22, will be used as a quantitative phenotype in the molecular genetic phase of GENESiS.

Adult↗
PubMed1999

DNA pooling and dense marker maps: a systematic search for genes for cognitive ability.

Pooling DNA from subjects within a group and comparing the pooled DNA across groups for a dense map of DNA markers offers a solution to the conundrum that linkage is systematic but not powerful whereas allelic association is powerful but not systematic. We used DNA pooling to screen 66 markers on chromosome 22 in original and replication samples of children of high general cognitive ability (g) and controls of average g. Although none of these markers survived our three-stage screening design (original pooling, replication pooling, individual genotyping), the results of DNA pooling were largely confirmed by individual genotyping. We can therefore exclude associations of major effect size on chromosome 22 for g, a key variable for cognitive neuroscience research on learning and memory.

Alleles↗
PubMed1999

Human power output during repeated sprint cycle exercise: the influence of thermal stress.

Thermal stress is known to impair endurance capacity during moderate prolonged exercise. However, there is relatively little available information concerning the effects of thermal stress on the performance of high-intensity short-duration exercise. The present experiment examined human power output during repeated bouts of short-term maximal exercise. On two separate occasions, seven healthy males performed two 30-s bouts of sprint exercise (sprints I and II), with 4 min of passive recovery in between, on a cycle ergometer. The sprints were performed in both a normal environment [18.7 (1.5) degrees C, 40 (7)% relative humidity (RH; mean SD)] and a hot environment [30.1 (0.5) degrees C, 55 (9)% RH]. The order of exercise trials was randomised and separated by a minimum of 4 days. Mean power, peak power and decline in power output were calculated from the flywheel velocity after correction for flywheel acceleration. Peak power output was higher when exercise was performed in the heat compared to the normal environment in both sprint I [910 (172) W vs 656 (58) W; P < 0.01] and sprint II [907 (150) vs 646 (37) W; P < 0.05]. Mean power output was higher in the heat compared to the normal environment in both sprint I [634 (91) W vs 510 (59) W; P < 0.05] and sprint II [589 (70) W vs 482 (47) W; P < 0.05]. There was a faster rate of fatigue (P < 0.05) when exercise was performed in the heat compared to the normal environment. Arterialised-venous blood samples were taken for the determination of acid-base status and blood lactate and blood glucose before exercise, 2 min after sprint I, and at several time points after sprint II. Before exercise there was no difference in resting acid-base status or blood metabolites between environmental conditions. There was a decrease in blood pH, plasma bicarbonate and base excess after sprint I and after sprint II. The degree of post-exercise acidosis was similar when exercise was performed in either of the environmental conditions. The metabolic response to exercise was similar between environmental conditions; the concentration of blood lactate increased (P < 0.01) after sprint I and sprint II but there were no differences in lactate concentration when comparing the exercise bouts performed in a normal and a hot environment. These data demonstrate that when brief intense exercise is performed in the heat, peak power output increases by about 25% and mean power output increases by 15%; this was due to achieving a higher pedal cadence in the heat.

Acid-Base Equilibrium↗
PubMed1999

Fatigue profile: a numerical method to examine fatigue in cycle ergometry.

Fatigue Profile, a new numerical method for characterising fatigue in isokinetic cycle ergometry is presented and compared with the conventional fatigue index (FI). The new method describes the temporal development of muscle fatigue based on the decline of peak power output throughout a whole trial. The advantage of this method is demonstrated by the analysis of two 25 s maximum trials, separated by 90 s recovery, performed by a well-trained athlete at a pedal frequency of 120 revolutions per minute. A fourth degree polynomial was fitted to model the peak power data. Using the polynomial model coefficients the first derivative represented the rate of changing peak power which represented the Fatigue Profile. The conventional FI was calculated as -35 Ws(-1) and -32 Ws(-1) for trials 1 and 2 respectively, indicating minor differences in fatigue between trials. In contrast the Fatigue Profile revealed important numeric and temporal differences between the trials. For trial 1 a maximum rate of peak power decline of -65 Ws(-1) was reached at approximately 6 s into the trial. In marked contrast, in trial 2, maximum rate of peak power decline (-146 Ws(-1)) occurred immediately. The Fatigue Profile approach allows the characterisation of the temporal development of fatigue under different experimental conditions and in combination with other techniques may yield further insight into the underlying mechanisms of fatigue.

Adult↗
PubMed1999

A randomised phase III study of accelerated or standard fraction radiotherapy with or without concurrent carboplatin in inoperable non-small cell lung cancer: final report of an Australian multi-centre trial.

PURPOSE: To investigate the effects separately and together of (a) shortening overall treatment time and (b) giving concurrent carboplatin in patients having radical radiotherapy for inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between April 1989 and May 1995, 204 patients with medically inoperable or technically unresectable NSCLC localised to the primary site and regional lymph nodes were randomised to receive one of four treatments using a 2 x 2 factorial design: standard radiotherapy, 60 Gy in 30 fractions in 6 weeks (R6); accelerated radiotherapy, 60 Gy in 30 fractions in 3 weeks (R3); standard radiotherapy as in R6 with carboplatin 70 mg/m2/day for 5 days during weeks 1 and 5 of radiotherapy (R6C); accelerated radiotherapy as in R3 with carboplatin 70 mg/m2/day for 5 days during week 1 of radiotherapy (R3C). RESULTS: The estimated median survival of all randomised patients was 15.7 months and estimated 2-year survival was 31%. The longest survival was seen in patients randomised to R6C (median 20.3 months, 41% surviving at 2 years) but there were no statistically significant differences between treatment arms or treatment factors (carboplatin versus no carboplatin, accelerated versus conventional radiotherapy). Haematological toxicity was significantly greater in patients treated with carboplatin and oesophageal toxicity was significantly greater and more protracted in patients treated with accelerated radiotherapy. CONCLUSIONS: This study failed to show a significant survival advantage for any of the treatment arms or factors. Halving overall treatment time resulted in significantly greater oesophageal toxicity with no suggestion of a survival advantage.

Adult↗
PubMed1999

Association between variants at the GABAAbeta2, GABAAalpha6 and GABAAgamma2 gene cluster and alcohol dependence in a Scottish population.

A role for the GABA/benzodiazepine receptor complex in alcohol dependence syndrome has been suggested by several lines of evidence. To elucidate the role of GABAA subunits in human alcohol dependence syndrome, we identified polymorphisms in the GABAAbeta2 and GABAAalpha6 receptor subunit genes on 5q33 and assessed their potential contribution in an association study, together with a NciI RFLP at the GABAAgamma2 receptor subunit gene. One hundred and eight alcohol-dependent subjects and 54 unrelated controls were recruited from Scotland. Two novel genetic markers were identified at the GABAAbeta2 and GABAAalpha6 receptor subunit genes and examined for association with the alcohol dependence syndrome and subgroups of subjects with Korsakoff's psychosis and without Korsakoff's psychosis, together with a NciI RFLP at the GABAAgamma2 receptor subunit gene. The chi2 tests demonstrated associations between all alcohol-dependent subjects (not stratified) and the BanI RFLP at the GABAAbeta2 receptor subunit gene (P = 0.015), and the AlwNI RFLP at the GABAAalpha6 receptor gene (P = 0.013). Significant associations were also found between the alcohol-dependent subjects with Korsakoff's psychosis and the BanI RFLP (P = 0.039) and the AlwNI RFLP (P = 0.003). Haplotype analysis also provided evidence of association when all alcohol-dependent subjects (P = 0.013) and the subjects with Korsakoff's psychosis (P = 0.007) were compared with controls. Our findings provide evidence for a role for the GABAA receptor subunit cluster on chromosome 5q33 in susceptibility to the alcohol dependence syndrome and Korsakoff's psychosis.

Adult↗
PubMed1999

DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in children.

General cognitive ability (g), which is related to many aspects of brain functioning, is one of the most heritable traits in neuroscience. Similarly to other heritable quantitatively distributed traits, genetic influence on g is likely to be due to the combined action of many genes of small effect [quantitative trait loci (QTLs)], perhaps several on each chromosome. We used DNA pooling for the first time to search a chromosome systematically with a dense map of DNA markers for allelic associations with g. We screened 147 markers on chromosome 4 such that 85% of the chromosome were estimated to be within 1 cM of a marker. Comparing pooled DNA from 51 children of high g and from 51 controls of average g, 11 significant QTL associations emerged. The association with three of these 11 markers ( D4S2943, MSX1 and D4S1607 ) replicated using DNA pooling in independent samples of 50 children of extremely high g and 50 controls. Furthermore, all three associations were confirmed when each individual was genotyped separately ( D4S2943, P = 0. 00045; MSX1, P = 0.011; D4S1607, P = 0.019). Identifying specific genes responsible for such QTL associations will open new windows in cognitive neuroscience through which to observe pathways between genes and learning and memory.

Adolescent↗
PubMed1999

Contact between people with learning disability and general practitioners: a cross-sectional case note survey.

BACKGROUND: This paper describes primary care consultation rates in a sample of people with learning disability. The study was carried out as part of a wider survey of primary care for this population group in response to concerns over quality of care and debate between general practitioners (GPs) and the local health authority over the need for additional remuneration for caring for people with learning disability. Estimates of consultation rates in the literature to date are conflicting and we sought to provide local data on the number and type of contacts with the primary care teams to inform this debate. METHOD: A primary care case note review was carried out of 112 people with learning disability aged over 18, identified from an administrative sample of 967 people known to health and social services. Contact rates (with practice nurses or GPs) were calculated and indirectly standardized for age using data from the fourth National Morbidity Survey in General Practice (MSGP4). RESULTS: Standardized consultation ratio in men was 156 (95 per cent confidence interval (CI) 142-172), in women was 111 (95 per cent CI 102-121) and for both sexes was 127 (95 per cent CI 120-135). Average contact rate was 4.6 per person per year. Eighty per cent of contacts were with GPs. Eighteen per cent (95 per cent CI 11-25 per cent) of subjects consulted, on average, more than once every two months. Limited information on underlying cause of learning disability and severity was available. Consultation rates were independent of age and sex, and were not increased in people with Down's syndrome or epilepsy compared with the rest of the sample population. Consultation rates were highest in people living in staffed group homes (p = 0.01). The presence of special arrangements between practices and residential facilities did not appear to increase service contact, but this finding is prone to measurement bias. CONCLUSIONS: Contrary to the findings of previous studies, people with learning disability consult primary care teams more frequently than the general population. However, this should not be taken as supporting calls for additional resources without addressing the effectiveness and appropriateness of health care offered.

Adult↗