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Biomedical subjects

C L Hart

Publications and source records attributed to C L Hart.

At least 55 records · Page 3Linked to original sources
PubMed1999

Identification of kinesin-C, a calmodulin-binding carboxy-terminal kinesin in animal (Strongylocentrotus purpuratus) cells.

Several novel members of the kinesin superfamily, until now identified only in plants, are unique in their ability to bind calmodulin in the presence of Ca(2+). Here, we identify the first such kinesin in an animal system. Sequence analysis of this new motor, called kinesin-C, predicts that it is a large carboxy-terminal kinesin, 1624 amino acid residues in length, with a predicted molecular mass of 181 kDa. Kinesin-C is predicted to contain a kinesin motor domain at its carboxy terminus, linked to a segment of alpha-helical coiled-coil 950 amino acid residues long, ending with an amino-terminal proline-rich tail domain. A putative calmodulin-binding domain resides at the extreme carboxy terminus of the motor polypeptide, and recombinant kinesin-C binds to a calmodulin-affinity column in a Ca(2+)-dependent fashion. The presence of this novel calmodulin-binding motor in sea urchin embryos suggests that it plays a critical role in Ca(2+)-dependent events during early sea urchin development.

Amino Acid Sequence↗
PubMed1999

Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of scottish men with 21 years of follow up.

OBJECTIVES: To relate alcohol consumption to mortality. DESIGN: Prospective cohort study. SETTING: 27 workplaces in the west of Scotland. PARTICIPANTS: 5766 men aged 35-64 when screened in 1970-3 who answered questions on their usual weekly alcohol consumption. MAIN OUTCOME MEASURES: Mortality from all causes, coronary heart disease, stroke, and alcohol related causes over 21 years of follow up related to units of alcohol consumed per week. RESULTS: Risk for all cause mortality was similar for non-drinkers and men drinking up to 14 units a week. Mortality risk then showed a graded association with alcohol consumption (relative rate compared with non-drinkers 1. 34 (95% confidence interval 1.14 to 1.58) for 15-21 units a week, 1. 49 (1.27 to 1.75) for 22-34 units, 1.74 (1.47 to 2.06) for 35 or more units). Adjustment for risk factors attenuated the increased relative risks, but they remained significantly above 1 for men drinking 22 or more units a week. There was no strong relation between alcohol consumption and mortality from coronary heart disease after adjustment. A strong positive relation was seen between alcohol consumption and risk of mortality from stroke, with men drinking 35 or more units having double the risk of non-drinkers, even after adjustment. CONCLUSIONS: The overall association between alcohol consumption and mortality is unfavourable for men drinking over 22 units a week, and there is no clear evidence of any protective effect for men drinking less than this.

Adult↗
PubMed1999

The health impact of smoking in manual and non-manual social class men and women: a test of the Blaxter hypothesis.

Blaxter has hypothesized that harmful behavioral habits like smoking have a greater impact on health in the non-manual than in the manual social classes, possibly because other adverse exposures have a more important role in the manual social classes. However, the outcome measure used was a composite measure of physiological indices of morbidity and the relevance of this to other health problems is uncertain. We have therefore investigated the effect of smoking on mortality, to test whether the risk of death associated with smoking differs between manual and non-manual social classes. Data on 6831 men and 7993 women, aged 45-64 when screened in the Renfrew and Paisley study, a large prospective observational study in the West of Scotland, have been analyzed. All cause mortality rate ratios for smokers compared with never smokers have been calculated within manual and non-manual social classes. Although the age adjusted rate ratios are slightly higher among the non-manual men and women (2.19 [1.83-2.61] versus 1.92 [1.71-2.17] for non-manual and manual men respectively, and 1.75 [1.54-1.99] versus 1.65 [1.50-1.82] for non-manual and manual women), this difference between social classes is not statistically significant (p-values for test of difference 0.26 and 0.47 for men and women respectively). When additionally adjusted for other risk factors, cardiorespiratory symptoms and deprivation, this picture remained the same (p-values for test of difference are 0.41 and 0.50 for men and women respectively). Similar results were found when the cohort was divided by deprivation categories rather than social classes or when smoking related mortality rather than mortality from all causes was used as the outcome measure. We therefore conclude that the health impact of smoking is similar in each socio-economic group. The relative health improvement consequent on smoking cessation is thus similar in different socio-economic groups.

Aged↗
PubMed1999

Risk factors and 20-year stroke mortality in men and women in the Renfrew/Paisley study in Scotland.

BACKGROUND AND PURPOSE: The aim of this study was to relate risk factors in middle-aged men and women to stroke mortality over a long follow-up period. METHODS: In the early to mid 1970s, 7052 men and 8354 women from the Renfrew/Paisley prospective cohort study in Scotland were screened when aged 45 to 64 years. Risk factors measured included blood pressure, blood cholesterol and glucose, respiratory function, cardiothoracic ratio, smoking habit, height, body mass index, age, preexisting coronary heart disease, and diabetes. These were related to stroke mortality over 20 years of follow-up. RESULTS: Women's stroke mortality rates were similar to men's, unlike coronary heart disease mortality, in which case women's rates were lower than men's. Diastolic and systolic blood pressure, smoking, cardiothoracic ratio, preexisting coronary heart disease, and diabetes were positively related to stroke mortality for men and women, while adjusted forced expiratory volume in 1 second and height were negatively related. Cholesterol and body mass index were not related to stroke mortality. Glucose in nondiabetics was positively related to stroke mortality for women but not men, and there was evidence of a threshold effect at the highest levels of glucose. Former smokers had mortality rates that were similar to those of never-smokers. In sex-specific multivariate models, most variables retained a statistically significant association with stroke mortality, illustrating the multifactorial etiology of stroke. CONCLUSIONS: Overall, findings for women were similar to those for men. Control of risk factors for reduction of stroke mortality should be targeted at men and women in a similar fashion, particularly with reference to smoking cessation and blood pressure control.

Blood Glucose↗
PubMed1998

Direction determination in the minus-end-directed kinesin motor ncd.

Motor proteins of the kinesin superfamily transport intracellular cargo along microtubules. Although different kinesin proteins share 30-50% amino-acid identity in their motor catalytic cores, some move to the plus end of microtubules whereas others travel in the opposite direction. Crystal structures of the catalytic cores of conventional kinesin (a plus-end-directed motor involved in organelle transport) and ncd (a minus-end-directed motor involved in chromosome segregation) are nearly identical; therefore, the structural basis for their opposite directions of movement is unknown. Here we show that the ncd 'neck' made up of 13 class-specific residues next to the superfamily-conserved catalytic core, is essential for minus-end-directed motility, as mutagenesis of these neck residues reverses the direction of ncd motion. By solving the 2.5 A structure of a functional ncd dimer, we show that the ncd neck (a coiled-coil) differs from the corresponding region in the kinesin neck (an interrupted beta-strand), although both necks interact with similar elements in the catalytic cores. The distinct neck architectures also confer different symmetries to the ncd and kinesin dimers and position these motors with appropriate directional bias on the microtubule.

Cloning, Molecular↗
PubMed1998

Social mobility and 21 year mortality in a cohort of Scottish men.

The objective of this prospective cohort study was to determine the contribution of changes in social class within and between generations to mortality risk and to socioeconomic differentials in mortality. In 27 workplaces in the west of Scotland. 5567 men aged 35-64 years when screened, provided information on their father's occupation, their own first occupation and their occupation at screening. Mortality risk, from broad causes of death by intergenerational and intragenerational social mobility groups, was measured after 21 years. For all or some of the 3 routes of mobility (childhood to screening, labour market entry to screening and childhood to labour market entry), increasing values were seen across the 4 groups (stable non manual, upwardly mobile, downwardly mobile and stable manual) for diastolic blood pressure, body mass index, current smoking, early school leaving, angina, bronchitis, severe chest pain, and proportion living in deprived areas. Decreasing values were seen for serum cholesterol, height, FEV1, exercise, never and ex-smokers, wine drinkers and car users. For mobility between childhood and screening and between childhood and labour market entry, mortality risk was highest for the stable manual group and lowest for the stable non manual group for all cause, cardiovascular disease and other causes of death. The upwardly and downwardly mobile groups had intermediate risks. For cancer mortality, the stable manual group had the highest risk with the other groups having lower and similar risks. For mobility between labour market entry and screening, the highest risk was for the downwardly mobile group for all cause and cardiovascular mortality. For cancer mortality, the risk was higher for men in manual social classes at all occasions. Adjustment for risk factors attenuated but could not completely explain the differentials in mortality risk. Overall, major differences in mortality risk were seen between the stable non manual and the stable manual groups, to which social mobility does not contribute. With the exception of the small intragenerationally downwardly mobile group there was little evidence that social mobility itself was associated with mortality outcomes different from those expected on the basis of lifetime socioeconomic experience. This is consistent with the suggestion that the main influence of socioeconomic position on mortality risk is an accumulative one, acting across the lifecourse.

Adult↗
PubMed1998

Socioeconomic differentials in mortality among men within Great Britain: time trends and contributory causes.

STUDY OBJECTIVE: To assess the size of mortality differentials in men by social class in Scotland as compared with England and Wales, and to analyse the time trends in these differentials. SUBJECTS: Men from England and Wales and Scotland around each census from 1951 to 1981. METHODS: Poisson regression analysis was used to calculate relative indices of inequality for disease specific and all cause mortality as a measure of mortality differentials between social classes. This measure is not dependent on the size of the social class groups, so it can be used to compare the magnitude of differentials over time periods during which the relative sizes of social class groups change. MAIN RESULTS: While overall death rates were higher in Scotland than in England and Wales around the 1951, 1961, and 1971 censuses the relative indices of inequality indicated smaller mortality differences between social classes in Scotland. Inequality, as indexed by the relative index of inequality, increased over time in both Scotland and England and Wales, but to a greater degree in Scotland, resulting in greater social class mortality differentials for Scotland in 1981 (the relative index of inequality increased from 1.40 to 2.43 for England and Wales, and from 1.22 to 2.57 for Scotland between 1951 and 1981). This greater increase in the magnitude of inequalities in all cause mortality in Scotland seemed to result from increasing social class differentials in cardiovascular disease, accidents and external causes, and "all other causes of death". Examining the trends in overall death rates, it seems that the greater increase in social class differences in Scotland occurred because of the greater decrease in death rates among the privileged social groups, in combination with a smaller decrease (or a greater increase) in the death rates in the lower social class groups. CONCLUSIONS: This study has shown that trends in mortality and in inequalities in mortality differ within Great Britain. Although death rates were higher in Scotland than in England and Wales, smaller mortality differentials by social class were found in Scotland over the period 1951 to 1971. By 1981, however, social class mortality differentials were greater in Scotland than in England and Wales. The greater increase in the social class differentials over time in Scotland, may have contributed to the worsening overall mortality profile in Scotland as compared with England and Wales that occurred between 1971 and 1981.

Adolescent↗
PubMed1998

Inequalities in mortality by social class measured at 3 stages of the lifecourse.

OBJECTIVES: This study examined how social class, measured at 3 staged of life, contributes to mortality risk. METHODS: A cohort of employed Scottish men (n = 5567) provided their fathers' occupation and their own first and current occupations, from which social class in childhood, at labor-market entry, and at screening (1970 to 1973) was determined. Relative rates of mortality and relative indices of inequality were calculated from 21 years of follow-up. RESULTS: Mortality risk was similar at each stage of life, with men in the higher social classes having the lowest risk. Social class at screening produced the greatest relative indices of inequality. CONCLUSIONS: The widening of inequalities in mortality in adulthood suggests the importance of the accumulation of poor socioeconomic circumstances throughout life.

Adult↗
PubMed1998

The Bruce treadmill protocol: does walking or running during the fourth stage alter oxygen consumption values?

OBJECTIVE: To investigate heart rate (HR) and relative oxygen consumption (VO2) measures during two modes (walking or running stages four) of the Bruce treadmill protocol. PARTICIPANTS: Male volunteers (n = 27), ranging in age from 25 to 56 years (M = 39.1 +/- 10.7 yrs). EXPERIMENTAL DESIGN: S's performed to volitional fatigue on the two randomly assigned treadmill tests. MEASURES: HR and VO2 were taken each minute and at point of exhaustion. RESULTS: Dependent "t"-tests revealed a significantly (p < or = 0.05) difference between the protocols at 11 minutes (running = 46.7 +/- 3.9 > walking = 44.6 +/- 3.7 ml[kg.min-1]) and at 12 minutes (running = 49.3 +/- 4.1 > walking = 47.6 +/- 3.5 ml[kg.min-1]) on the VO2 values. A significant differences was noted on HR at 11 minutes (running = 158.1 +/- 13.5 > walking = 156.0 +/- 13.0 bpm) and at 12 minutes (running = 160.4 +/- 11.0 > walking = 157.8 +/- 11.4 bpm) between the protocols. The two-way ANOVA technique revealed no significant differences or interactions on VO2 or HR between younger (< 45 yrs) and older (> or = 45 yrs) subjects during either protocol. A one-way ANCOVA indicated no significant differences between taller and shorter subjects on VO2 during the fourth stage of the Bruce protocol. The correlations, between the two protocols, for HR were strong but were weaker and inconsistent for VO2. The repeated measures ANOVA indicated significant within subject variability between test administrations. CONCLUSIONS: When testing endurance trained males, modality, age and height are not factors in differences of VO2 values during the 4th stage of the Bruce treadmill test but learning effect could be.

Adult↗
PubMed1997

The directional preference of kinesin motors is specified by an element outside of the motor catalytic domain.

Members of the kinesin superfamily share a similar motor catalytic domain yet move either toward the plus end (e.g., conventional kinesin) or the minus end (e.g., Ncd) of microtubules. The structural features that determine the polarity of movement have remained enigmatic. Here, we show that kinesin's catalytic domain (316 residues) in a dimeric construct (560 residues) can be replaced with the catalytic domain of Ncd and that the resultant motor moves in the kinesin direction. We also demonstrate that this chimera does not move processively over many tubulin subunits, which is similar to Ncd but differs from the highly processive motion of conventional kinesin. These findings reveal that the catalytic domain contributes to motor processivity but does not control the polarity of movement. We propose that a region adjacent to the catalytic domain serves as a mechanical transducer that determines directionality.

Adenosine Triphosphatases↗
PubMed1997

Microtubule interaction site of the kinesin motor.

Kinesin and myosin are motor proteins that share a common structural core and bind to microtubules and actin filaments, respectively. While the actomyosin interface has been well studied, the location of the microtubule-binding site on kinesin has not been identified. Using alanine-scanning mutagenesis, we have found that microtubule-interacting kinesin residues are located in three loops that cluster in a patch on the motor surface. The critical residues are primarily positively charged, which is consistent with a primarily electrostatic interaction with the negatively charged tubulin molecule. The core of the microtubule-binding interface resides in a highly conserved loop and helix (L12/alpha5) that corresponds topologically to the major actin-binding domain of myosin. Thus, kinesin and myosin have developed distinct polymer-binding domains in a similar region with respect to their common catalytic cores.

Adenosine Triphosphatases↗
PubMed1997

Pre-existing ischaemic heart disease and ischaemic heart disease mortality in women compared with men.

BACKGROUND: In all 8353 women and 7058 men aged 45-64 took part in the Renfrew/Paisley survey in 1972-1976. They formed a prospective cohort study of a general population in the West of Scotland; an area with high ischaemic heart disease (IHD) mortality rates. The objective of this study was to investigate three indicators of pre-existing IHD and determine how they predicted subsequent IHD mortality in females compared with males. METHODS: Pre-existing IHD was ascertained by the Rose Angina questionnaire, a question on severe chest pain indicating evidence of previous IHD and an electrocardiogram at a screening examination. Mortality information for a 15-year follow-up period was available. RESULTS: Pre-existing IHD was higher at older ages and was less common in women than men. The risks of IHD mortality were doubled for those with a single cardiovascular indicator compared to those without, and were increased to fourfold for those with two or more indicators. Indicators of pre-existing IHD had high specificity and low sensitivity for subsequent IHD mortality in both women and men, and the positive predictive values for women in the oldest age group were similar to those for men in the youngest age group. CONCLUSIONS: Each indicator of pre-existing IHD was a useful predictor of subsequent IHD mortality in both women and men, even though IHD mortality rates were lower in women. The indicators obtained by questionnaire could be implemented in the primary health care setting to identify quickly those at risk who would benefit from further investigation and intervention.

Age Factors↗
PubMed1996

Association of cardiovascular disease risk factors with socioeconomic position during childhood and during adulthood.

OBJECTIVE: To investigate strength of associations between risk factors for cardiovascular disease and socioeconomic position during childhood and adulthood. DESIGN: Cross sectional analysis of status of cardiovascular risk factors and past and present social circumstances. SUBJECTS: 5645 male participants in the west of Scotland collaborative study, a workplace screening study. MAIN OUTCOME MEASURES: Strength of association between each risk factor for cardiovascular disease (diastolic blood pressure, serum cholesterol concentration, level of recreational physical exercise, cigarette smoking, body mass index, and FEV1 score (forced expiratory volume in one second as percentage of expected value) and social class during childhood (based on father's main occupation) and adulthood (based on own occupation at time of screening). RESULTS: All the measured risk factors were significantly associated with both father's and own social class (P < 0.05), apart from exercise and smoking (not significantly associated with father's social class) and body mass index (not significantly associated with own social class). For all risk factors except body mass index, the regression coefficient of own social class was larger than the regression coefficient of father's social class. The difference between the coefficients was significant for serum cholesterol concentration, cigarette smoking, body mass index, and FEV1 score (all P < 0.001). CONCLUSIONS: Subjects' status for behavioural risk factors (exercise and smoking) was associated primarily with current socioeconomic circumstances, while status for physiological risk factors (serum cholesterol, blood pressure, body mass index, and FEV1) was associated to varying extents with both past and present socioeconomic circumstances.

Adult↗
PubMed1996

Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study.

OBJECTIVE: To assess the relation between forced expiratory volume in one second (FEV1) and subsequent mortality. DESIGN: Prospective general population study. SETTING: Renfrew and Paisley, Scotland. SUBJECTS: 7058 men and 8353 women aged 45-64 years at baseline screening in 1972-6. MAIN OUTCOME MEASURE: Mortality from all causes, ischaemic heart disease, cancer, hung and other cancers, stroke, respiratory disease, and other causes of death after 15 years of follow up. RESULTS: 2545 men and 1894 women died during the follow up period. Significant trends of increasing risk with diminishing FEV1 are apparent for both sexes for all the causes of death examined after adjustment for age, cigarette smoking, diastolic blood pressure, cholesterol concentration, body mass index, and social class. The relative hazard ratios for all cause mortality for subjects in the lowest fifth of the FEV1 distribution were 1.92 (95% confidence interval 1.68 to 2.20) for men and 1.89 (1.63 to 2.20) for women. Corresponding relative hazard ratios were 1.56 (1.26 to 1.92) and 1.88 (1.44 to 2.47) for ischaemic heart disease, 2.53 (1.69 to 3.79) and 4.37 (1.84 to 10.42) for lung cancer, and 1.66 (1.07 to 2.59) and 1.65 (1.09 to 2.49) for stroke. Reduced FEV1 was also associated with an increased risk for each cause of death examined except cancer for lifelong nonsmokers. CONCLUSIONS: Impaired lung function is a major clinical indicator of mortality risk in men and women for a wide range of diseases. The use of FEV1 as part of any health assessment of middle aged patients should be considered. Smokers with reduced FEV1 should form a priority group for targeted advice to stop smoking.

Cardiovascular Diseases↗
PubMed1995

Cardiorespiratory disease in men and women in urban Scotland: baseline characteristics of the Renfrew/Paisley (midspan) study population.

UNLABELLED: STUDY OBJECTIVE. To describe the distribution of risk factors, risk behaviors, symptoms and the prevalence of cardiorespiratory disease in men and women in an urban area with high levels of socioeconomic deprivation. A cross-sectional survey of 15,411 men and women aged 45-64, comprising an 80% response rate from the general population in Paisley and Renfrew, Scotland. MAIN RESULTS: The main characteristics of the male Renfrew/Paisley population, compared to previous British studies, were shorter stature, higher blood pressure, a higher proportion of smokers who continue to smoke, lower FEV1 and higher levels of reported angina, breathlessness on effort and chronic bronchitis. In comparison with men, the main characteristics of the female Renfrew/Paisley population were shorter stature, higher plasma cholesterol, lower FEV1, fewer current and ex-smokers, and a higher prevalence of breathlessness on effort. There were only small differences between men and women in the prevalence of angina, ECG evidence of myocardial ischaemia and chronic bronchitis. CONCLUSIONS: Middle-aged men and women in an urban area with high levels of socio-economic deprivation have different cardio-respiratory risk and disease profiles compared to previous population in the UK, based on occupational groups and random national samples.

Angina Pectoris↗
PubMed1995

Risk factors for cardiorespiratory and all cause mortality in men and women in urban Scotland: 15 year follow up.

STUDY OBJECTIVE: To describe the relationship between risk factors, risk behaviours, symptoms and mortality from cardiorespiratory diseases in an urban area with high levels of socioeconomic deprivation. A cohort study of 15,411 men and women aged 45-64, comprising 80% of the general population of Paisley and Renfrew, Scotland. OUTCOMES: Mortality after 15 years from coronary heart disease(ICD 410-4), stroke(ICD 430-8), respiratory disease(ICD 460-519) and all causes. MAIN RESULTS: Mortality rates from all causes were 19% in men aged 45-49, 31% in men aged 50-54, 42% in men aged 55-59 and 57% in men aged 60-64. The rates are considerably higher than those reported in previous UK prospective studies. For women the rates were 12%, 18%, 25% and 38% respectively. In general men and women showed similar relationships between risk factor levels and mortality rates. People in manual occupations had higher mortality rates. Raised levels of systolic and diastolic blood pressure were associated with increased coronary, stroke and all cause mortality rates. Plasma cholesterol had no such association with all cause mortality rates. High and low levels of body mass index were associated with higher mortality rates than intermediate levels. A relationship between short stature and increased mortality rates was observed in men and women. FEV1 expressed as a percentage of the expected value showed the strongest relationship with mortality rates, particularly for respiratory disease, but also for deaths from coronary heart disease, stroke and all causes. CONCLUSIONS: A similar pattern of relationship between risk factor levels and mortality rates exists in men and women in Renfrew and Paisley. Respiratory impairment as measured by FEV1% predicted appears to be the most likely explanation of the observed high all cause mortality rates in this population.

Blood Pressure↗
PubMed1994

Predictability of sacral base levelness based on iliac crest measurements.

A level sacral base plane is necessary to allow normalization of complex lumbosacral mechanics. Palpatory examinations are often used to evaluate for leg length discrepancy and pelvic obliquity despite improved accuracy and consistency of radiographic techniques. Treatment based on palpatory examinations suppose a direct and consistent relationship between the pelvic bones (innominates) and the sacral base. To evaluate the relationship between iliac crest levelness and sacral base levelness, a radiographic postural survey in the upright, weight-bearing position was performed on 358 men and women thought to have pelvic obliquity. Of these subjects, 293 demonstrated unlevel iliac crest heights or sacral base > or = 3/16 inch (4.76 mm), with iliac crest heights accurately predicting sacral base position 62% of the time. At > or = 3/8 inch (9.53 mm), 68% of the cases were accurately predicted. When the criterion for unlevelness was increased to > or = 1/2 inch (12.70 mm), the predictive accuracy improved to 83%. Radiographic findings in this study demonstrate a significant difference between iliac crest heights and sacral base position. In cases of mild to moderate short leg syndromes, the iliac crest height is an unreliable predictor of the direction or degree of sacral base levelness.

Adult↗