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Biomedical subjects

D G Cook

Publications and source records attributed to D G Cook.

At least 91 records · Page 5Linked to original sources
PubMed1994

Passive exposure to tobacco smoke in children aged 5-7 years: individual, family, and community factors.

OBJECTIVE: To examine the importance of parental smoking on passive exposure to tobacco smoke in children and the social and geographical patterns of exposure. DESIGN: Cross sectional study. SETTING: Schools in 10 towns in England and Wales; five towns with high adult cardiovascular mortality and five with low rates. SUBJECTS: 4043 children aged 5-7 years of European origin. MAIN OUTCOME MEASURES: Salivary cotinine concentration and parents self reported smoking habits. RESULTS: 1061 (53.0%) children were exposed to cigarette smoke at home or by an outside carer. Geometric mean cotinine rose from 0.29 (95% confidence interval 0.28 to 0.31) ng/ml in children with no identified exposure to 4.05 (3.71 to 4.42) ng/ml in households where both parents smoked and 9.03 (6.73 to 12.10) ng/ml if both parents smoked more than 20 cigarettes a day. The effect of mothers' smoking was greater than that of fathers', especially at high levels of consumption. After adjustment for known exposures geometric mean cotinine concentrations rose from 0.52 ng/ml in social class I to 1.36 ng/ml in social class V (P < 0.0001); and were doubled in high mortality towns compared with the low mortality towns (P = 0.002). In children with no identified exposure similar trends by social class and town were observed and the cotinine concentrations correlated with the prevalence of parental smoking, both between towns (r = 0.69, P = 0.02) and between schools within towns (r = 0.50, P < 0.001). CONCLUSIONS: Mothers' smoking is more important that fathers' despite the lower levels of smoking by mothers. Children not exposed at home had low cotinine concentration, the level depending on the prevalence of smoking in the community.

Age Factors↗
PubMed1994

Binding of human immunodeficiency virus type I (HIV-1) gp120 to galactosylceramide (GalCer): relationship to the V3 loop.

The primary receptor for the human immunodeficiency virus (HIV) is the CD4 molecule. However, a large body of evidence has demonstrated that some cells that do not express the CD4 receptor can be infected by HIV-1 and HIV-2, indicating that an alternative mechanism of infection must exist for some cell types. Recently it was reported that antibodies against the glycosphingolipid, galactosylceramide (Gal beta 1-1'Cer;GalCer), blocked infection of several CD4 negative cell lines derived from the brain and colon. The hypothesis that GalCer might be involved in the process of HIV entry into these cells was further supported by the finding that recombinant gp120 bound GalCer with high affinity in a high performance thin layer chromatography (HPTLC) binding assay. We have examined the interactions between GalCer and gp120, and found that the oligosaccharides that constitute a large proportion of the molecular mass of this glycoprotein are not involved in binding to this glycolipid. Furthermore, using a panel of monoclonal and monospecific antibodies we have determined that gp120 binds GalCer, and the related molecule 3' sulfo galactosylceramide (sulfatide), at a site that is conformationally close to the its principal neutralizing domain (V3 loop) or at the V3 loop itself.

Animals↗
PubMed1994

Expression of foreign proteins in a human neuronal system.

The NT2N cell system offers an attractive way to overcome some of the technical limitations inherent in working with primary neuronal cultures. In particular, it is possible to obtain large quantities of neurons with which to perform biochemical experiments, and the growth of neurites can be synchronized and controlled by varying the substrate on which the cells grow. In addition, because the differentiated NT2N neurons are derived from a mitotically active precursor cell line in vitro, it is possible to employ a variety of techniques, that are not otherwise available when working directly with postmitotic neurons, to obtain expression of foreign proteins. Because they are fully polarized, NT2N cells offer a way to study protein sorting to axons and dendrites at both the biochemical and the morphological level. Further characterization of NT2N cells is underway, and more efficient ways to obtain expression of foreign proteins will no doubt be found.

Base Sequence↗
PubMed1994

A comparison of bone mineral density between Caucasian, Asian and Afro-Caribbean women.

1. We analysed the lumbar spine (L2-L4) and femoral neck bone mineral density results of Caucasian (n = 2232), Asian (Indian sub-continent) (n = 153) and Afro-Caribbean (n = 102) women referred for bone densitometry over a 30 month period. To assess the risk of osteoporosis, the results of Caucasian and Asian women were compared with those of a reference Caucasian population supplied by Lunar. 2. Subject characteristics were similar in all three groups, other than expected ethnic differences in stature and weight. We found that lumbar spine and femoral neck bone mineral density in Caucasians was lower than in Afro-Caribbeans, but higher than in Asians. Consistent with this, bone mineral density was also lower in Asians as compared with the reference Caucasian population, both at the lumbar spine and femoral neck. As a consequence, a higher proportion of Asian women were classified as being at increased risk of osteoporosis than Caucasian women. 3. Since ethnic differences in skeletal size might influence bone mineral density, we also obtained values for bone mineral content in Caucasian and Asian women that were corrected for projected skeletal area, and weight and years since menopause, using regression equations derived from the Caucasian study population. After this analysis, the difference in bone mineral content between Caucasians and Asians at the lumbar spine disappeared, while that at the femoral neck persisted. 4. We conclude that the assessment of risk of osteoporosis in Asian women by comparing bone mineral density with a reference Caucasian population may have limited validity because of the influence of skeletal size on such measurements.

Absorptiometry, Photon↗
PubMed1994

Chest illness in infancy and chronic respiratory disease in later life: an analysis by month of birth.

BACKGROUND: Cohorts born at different times of year differ in their risk of exposure to seasonal respiratory infections in early life, but are likely to have similar socioeconomic status and lifestyle thereafter. METHODS: We investigated the long-term consequences of acute chest illness in infancy for later development of chronic respiratory disease by analysing variations by month of birth in hospital admissions for respiratory illness (total n = 49,866), chronic respiratory symptoms and ventilatory function among British school children (n = 11,482) and middle-aged adults (total n = 55,829). RESULTS: Admission for bronchiolitis in the first year of life was three times more common for infants born September to November (autumn) than those born March to May, yet people born in the autumn experienced fewer respiratory symptoms and had better ventilatory function. In two surveys of middle-aged men, forced expiratory volume in one second/forced ventilatory capacity (FEV1/FVC) was significantly (P = 0.025) higher among autumn births. Hospital admissions for chronic bronchitis/emphysema and pneumonia varied little with season of birth. Admissions for asthma were significantly (P < 0.05) more common among children and young adults born in the autumn. CONCLUSIONS: These findings do not support the hypothesis of a causal link between chest illness in infancy and the later development of chronic bronchitis and emphysema. The variation in asthma admissions with month of birth deserves further investigation.

Adult↗
PubMed1994

Characterization of human immunodeficiency virus type 1 gp120 binding to liposomes containing galactosylceramide.

Human immunodeficiency virus type 1 (HIV-1) infects some cell types which lack CD4, demonstrating that one or more alternative viral receptors exist. One such receptor is galactosylceramide (GalCer), a glycosphingolipid distributed widely in the nervous system and in colonic epithelial cells. Using a liposome flotation assay, we found that the HIV-1 surface glycoprotein, gp120, quantitatively bound to liposomes containing GalCer but not to liposomes containing phospholipids and cholesterol alone. Binding was saturable and was inhibited by preincubating liposomes with anti-GalCer antibodies. We observed less efficient binding of gp120 to liposomes containing lactosylceramide, glucosylceramide, and galactosylsulfate, whereas no binding to liposomes containing mixed gangliosides, psychosine, or sphingomyelin was detected. Binding to GalCer was rapid, largely independent of temperature and pH, and stable to conditions which remove most peripheral membrane proteins. By contrast, gp120 bound to lactosylceramide could be removed by 2 M potassium chloride or 3 M potassium thiocyanate, demonstrating a less stable interaction. Removal of N-linked oligosaccharides on gp120 did not affect binding efficiency. However, as previously observed for CD4 binding, heat denaturation of gp120 prevented binding to GalCer. Finally, binding was critically dependent on the concentration of GalCer in the target membrane, suggesting that binding to glycolipid-rich domains occurs and that GalCer conformation may be important for gp120 recognition.

Galactosylceramides↗
PubMed1993

Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor.

The gastrointestinal tract plays a major role in the pathogenesis and pathophysiology of infection by the type 1 human immunodeficiency virus (HIV-1). It is a potential route for viral entry and it is the site of a number of complications, including both opportunistic infections and a primary HIV-induced enteropathy. Correspondingly, both in vivo and in vitro studies have demonstrated HIV infection of gastrointestinal cells of lymphoid and epithelial origin. HT-29, a human colonic epithelial cell line that is infectable with many HIV-1 strains, does not express CD4 protein or mRNA. Recent studies showed that antibodies recognizing a neutral glycolipid related to galactosylceramide (GalCer) in HT-29 cells inhibited HIV-1 infection of this cell line, extending previous findings in neural cells. In the current studies, we further analyzed the neutral glycolipids of HT-29 cells and showed that they contained authentic GalCer and that recombinant gp120 bound to this glycolipid. Moreover, by analyzing GalCer expression in clones derived from HT-29 and Caco-2 (another human colonic cell line), we observed that the level of expression of this glycolipid was associated with the sensitivity to HIV-1 infection. Subclones of Caco-2 did not express GalCer and were not infectable with any of three HIV-1 strains. These results strengthen the possibility that GalCer is an alternative receptor in CD4- cell lines. Furthermore, since GalCer is a major glycolipid in epithelial cells of the small intestine and colon, these results provide a structural basis for the binding of HIV-1 by gastrointestinal epithelial cells and the entry of the virus into those cells.

Adenocarcinoma↗
PubMed1993

Time trends in respiratory symptoms in childhood over a 24 year period.

Two cross sectional surveys, 24 years apart, using the same respiratory questionnaire, were carried out to examine changes in prevalence rates of cough, phlegm, and wheeze and to relate changes in wheeze to objective peak expiratory flow rates (PEFRs). The surveys were done in towns in southern and northern England and South Wales in schoolchildren aged 6.0-7.5 years; n = 1655 in 1966 and n = 2323 in 1990. Parents reported on winter cough and winter phlegm (early morning or day/night) and wheeze; PEFRs were also measured. The proportion of children reported as wheezing on most days or nights increased from 3.9% to 6.1% (95% confidence interval (CI) for increase -0.2 to 4.6), with a smaller increase in the prevalence of those who had ever wheezed. The proportion of children with day or night time cough increased from 21.1% to 33.3% (95% CI for increase 3.8 to 20.6) and the proportion with day or night time phlegm increased from 5.8% to 10.0% (95% CI for increase 0.4 to 8.0). Smaller increases in the prevalence of persistent cough (from 9.0% to 12.4%) and persistent phlegm (from 2.4% to 3.5%) were also observed, while morning cough and morning phlegm showed little change. The increases in cough and phlegm were apparent in subjects with and without a history of wheeze. Both absolute and proportional changes in symptom prevalence were generally greater in the north than in the south. Similar social class trends were seen in each survey. The mean difference in PEFR between subjects with and without wheeze was smaller in 1990 than in 1966, but this result could be influenced by a greater proportion of subjects receiving antiasthmatic treatment in the 1990 survey. These apparent increases in the prevalence of persistent wheeze, day and night time cough and phlegm, occurring over a period during which outdoor air pollution levels have decreased substantially, deserve further investigation.

Child↗
PubMed1993

Relation of passive smoking as assessed by salivary cotinine concentration and questionnaire to spirometric indices in children.

BACKGROUND: Previous studies of the effects of passive exposure to smoke on spirometric indices in children have largely relied on questionnaire measures of exposure. This may have resulted in underestimation of the true effect of passive smoking. Biochemical measures offer the opportunity to estimate recent exposure directly. METHODS: The relation between spirometric indices and passive exposure to tobacco smoke was examined in a large population sample of 5-7 year old children from 10 towns in England and Wales. The effects of passive exposure to smoke on lung function were assessed by means of both salivary cotinine concentration and questionnaire measurements of exposure. Analyses of the relation between spirometric values and cotinine concentrations were based on 2511 children and of the relation between spirometric values and questionnaire measures on 2000 children. RESULTS: Cotinine concentration was negatively associated with all spirometric indices after adjustment for confounding variables, which included age, sex, body size, and social class. The strongest association was with mid expiratory flow rate (FEF50), the fall between the bottom and top fifths of the cotinine distribution being 6%, equivalent to a reduction of 14.3 (95% confidence limits (CL) 8.6, 20.0) ml/s per ng/ml cotinine. Salivary cotinine concentrations were strongly related to exposure to cigarette smoke at home but 88% of children who were from non-smoking households and not looked after by a smoker had detectable cotinine concentrations, 5% being in the top two fifths of the cotinine distribution. A composite questionnaire score based on the number of regular sources of exposure was as strongly related to mid and end expiratory flow rates as the single cotinine measure. The fall in FEF50 per smoker to whom the child was exposed was 51.0 (26.5, 75.5) ml/s. The relationships between the questionnaire score and forced vital capacity (FVC) or forced expiratory volume in one second (FEV1) were not statistically significant. CONCLUSIONS: These effects of passive smoking on respiratory function are consistent with the results of previous studies and, although small in absolute magnitude, may be important if the effects of exposure are cumulative. In children aged 5-7 years the use of a single salivary cotinine concentration as a marker of passive exposure to smoke resulted in clear relationships between exposure and FVC and FEV1, whereas the associations were much weaker and not significant when based on the questionnaire score. The associations between exposure and mid or end expiratory flow rates were of similar magnitude for cotinine concentration and the questionnaire score. The use of salivary cotinine concentration in longitudinal studies may help to determine the extent to which these effects are cumulative or reversible.

Biomarkers↗
PubMed1992

Leukocyte count and risk of major coronary heart disease events.

The association between leukocyte count and subsequent risk of major coronary heart disease events was examined using data from three prospective cohort studies--two from the United States and one from Great Britain. A total of 28,181 middle-aged men were followed for 6-12 years. A total of 1,768 men had a nonfatal myocardial infarction or died of coronary heart disease. In all three cohorts, there was a positive, statistically significant relation between baseline leukocyte count and risk of subsequent major coronary heart disease events after adjustment for age, serum total cholesterol, diastolic blood pressure, and number of cigarettes smoked per day (relative odds = 1.32 (p less than 0.0001), 1.15 (p = 0.0001), and 1.14 (p = 0.003), corresponding to a 2,000/mm3 difference in leukocyte count). The associations persisted when all nonsmokers (former smokers plus never smokers) and never smokers alone were considered and when those with evidence of preexisting coronary heart disease at baseline were excluded. Leukocyte count appears to be an indicator of a person's future risk of major coronary heart disease events.

Adult↗
PubMed1992

Non-employment and changes in smoking, drinking, and body weight.

OBJECTIVE: To assess the effect of unemployment and early retirement on cigarette smoking, alcohol consumption, and body weight in middle aged British men. DESIGN: Prospective cohort study (British regional heart study). SETTING: One general practice in 24 towns in Britain. SUBJECTS: 6057 men aged 40-59 who had been continuously employed for five years before the initial screening. Five years after screening 4412 men had been continuously employed and 1645 had experienced some unemployment or retired. MAIN OUTCOME MEASURES: Numbers of cigarettes smoked and units of alcohol consumed per week and body mass index (kg/m2). RESULTS: An initial screening significantly higher percentages of men who subsequently experienced non-employment smoked or had high alcohol consumption than of men who remained continuously employed: 43.0% versus 37.0% continuously employed for cigarette smoking (95% confidence interval for difference 3.2% to 9.0%) and 12.1% versus 9.0% for heavy drinking (1.3% to 5.1%). There was no evidence that men increased their smoking or drinking on becoming non-employed. Men non-employed through illness were significantly more likely to reduce their smoking and drinking than men who remained continuously employed. Men who experienced non-employment were significantly more likely to gain over 10% in weight than men who remained continuously employed: 7.5% versus 5.0% continuously employed (0.9% to 4.0%). CONCLUSIONS: Loss of employment was not associated with increased smoking or drinking but was associated with an increased likelihood of gaining weight. The long term effects of the higher levels of smoking and alcohol consumption before nonemployment should be taken into account when comparing mortality and morbidity in groups of unemployed and employed people.

Adult↗
PubMed1992

The leukocyte count and risk of lung cancer.

The association between leukocyte count and subsequent risk of lung cancer was evaluated in three large cohorts from the United States and Britain. A total of 309 lung cancer events occurred among 28,181 men whose cases were followed-up for 7 to 12 years. In all three cohorts, there was a marked increase in risk of lung cancer with increasing leukocyte count, after adjustment for age and the number of cigarettes smoked per day. The adjusted relative odds in the three cohorts, for a 2000/microliters difference in leukocyte count, were 1.58 (P = 0.0001), 1.29 (P = 0.003) and 1.20 (P = 0.02). These relative odds persisted when current smokers were considered alone, when serum markers of cigarette smoking exposure were adjusted for, and when men with lung cancer events during the first 5 years of follow-up were excluded. The leukocyte count appears to be linked to the pathogenesis of smoking-related lung cancer.

Adult↗
PubMed1992

Do maternal and intrauterine factors influence blood pressure in childhood?

It has been proposed that maternal health and nutrition may be important in the development of adult cardiovascular risk, and that blood pressure may be an important intermediate step in this process. To examine the relevance of this hypothesis in contemporary British children, the relationships of several maternal factors to blood pressure were studied in 3360 children of European origin aged 5-7 years. Maternal age, height, and body mass index were all positively related to blood pressure in childhood but these relationships were abolished once the child's body build was taken into account. Maternal social class, educational attainment, and history of smoking in pregnancy showed no relationship with blood pressure in childhood. Parity showed an inverse association with blood pressure, but this appeared to be due to an association between total sibship size and blood pressure, suggesting a postnatal rather than a prenatal origin. Blood pressure was higher in children whose mothers had a history of high blood pressure but this association was no stronger than that for paternal history. Both birth weight and gestational age were inversely related to blood pressure at 5-7 years. The association between birth weight and blood pressure was attenuated by standardisation for gestational age, and the relationships between birth weight and blood pressure were similar in preterm and full term infants. No specific association between blood pressure and the maternal factors studied have been observed in this population. Hypotheses relating maternal factors to cardiovascular risk need to specify the timing and nature of their effects more precisely. Although the relationship between birth weight and blood pressure is not fully understood, it appears to reflect size at birth rather than fetal growth rate.

Birth Weight↗
PubMed1992

The Dinamap 1846SX automated blood pressure recorder: comparison with the Hawksley random zero sphygmomanometer under field conditions.

STUDY OBJECTIVE: The aim was to compare the performance of the Dinamap 1846SX automated oscillometric blood pressure recorder with that of the Hawksley random zero sphygmomanometer during use under field study conditions. DESIGN: Two independent within subject measurement comparisons were made, one in adults and one in children, each conducted in three stages over several months while the Dinamap instruments were being used in epidemiological field surveys. SETTING: The studies were done in outpatients clinics (adults) and primary schools (children). PARTICIPANTS: 141 adults (20-85 years) and 152 children (5-7 years) took part. MEASUREMENTS AND MAIN RESULTS: In adults a pair of measurements was made with each instrument, the order alternating for consecutive subjects. In children one measurements was made with each instrument, in random order. Measurements with the Dinamap 1846SX were higher than those with the random zero sphygmomanometer both in adults (mean difference 8.1 mm Hg; 95% CI 6.5 to 9.7 mm Hg) and in children (mean difference 8.3 mm Hg; 95% CI 6.9 to 9.7 mm Hg). Diastolic measurements were on average very similar both in adults and in children. The results were consistent at all three stages of both studies. The differences in systolic measurement were independent of blood pressure level. However, the extent of agreement in diastolic pressure depended on the diastolic blood pressure level; in both studies Dinamap diastolic measurements were higher at low diastolic pressures while random zero diastolic measurements were higher at high diastolic pressures. CONCLUSIONS: Systolic measurements made with the Dinamap 1846SX instrument are not directly comparable with those of the Hawksley random zero sphygmomanometer and are unlikely to be comparable with those of earlier Dinamap models. These differences have important implications for clinical practice and for comparisons of blood pressure measurement between epidemiological studies. However, the consistency of measurement by the Dinamap 1846SX over time suggests that the instrument may have a place in standardised blood pressure measurement in the research setting.

Adult↗
PubMed1992

Childhood blood pressure, body build, and birthweight: geographical associations with cardiovascular mortality.

STUDY OBJECTIVE: The aim was to examine whether blood pressure, body build, and birthweight differ between areas of England and Wales with widely differing adult cardiovascular mortality rates. DESIGN: This was a cross sectional survey of children in five towns with exceptionally high and five towns with exceptionally low current adult cardiovascular mortality. SETTING: The study was a school based survey. SUBJECTS: 3842 children aged 5.0-7.5 years were selected by stratified random sampling of primary schools (response rate 76%). MEASUREMENTS AND MAIN RESULTS: Blood pressure, pulse rate, height, and weight were measured and birthweight was assessed by maternal recall. Children in towns with high cardiovascular mortality rates were significantly shorter than those in towns with low cardiovascular mortality rates (mean difference 0.9 cm, 95% confidence interval 0.4 to 1.4 cm) and had slightly higher body mass indices (mean difference 0.12 kg/m2, 95% CI -0.03 to 0.27 kg/m2). Mean birthweights were slightly lower in high mortality towns (mean difference 34 g, 95% CI -10 to 78 g), while the proportion of children with low birthweight (< 2500 g) (8.1%) was significantly higher than that in low mortality towns (5.5%) (p = 0.005). Mean differences in blood pressure between high and low mortality towns were small and non-significant, even after adjustment for height. The differences in height between high and low mortality towns were largely independent of social class. However, differences in mean birthweight were markedly reduced once social class was taken into account. CONCLUSIONS: No geographical relationship between childhood blood pressure and adult cardiovascular mortality was detected. Although it is possible that the differences in mean height and body mass index between towns with differing adult cardiovascular mortality may have implications for future patterns of health in these towns, the absence of marked differences in birthweight and blood pressure suggests that hypotheses proposing a direct relationship between intrauterine experience and adult cardiovascular mortality will have limited relevance to geographical variation in cardiovascular disease in this generation.

Adult↗
PubMed1992

Non-consulters and high consulters in general practice: cardio-respiratory health and risk factors.

The 1990 General Practitioner contract requires that health promotion and illness prevention services should be provided to all patients aged 16-74 years. Consultation rates over a period of three years were examined in 7010 middle-aged men in Great Britain to compare the cardio-respiratory health and risk factor status of non-consulters (men who did not consult in three years) with those of average consulters (men who consulted 3-5 times in three years) and high consulters (men who consulted 24 or more times in three years) to assess their relative need for health promotion and illness prevention services. The non-consulters (n = 1025) were remarkably similar to the average consulters (n = 1585) in health and lifestyle characteristics. The high consulters (n = 306) had a greater burden of ill-health and a less healthy lifestyle. Chest pain on exertion, chronic bronchitis, breathlessness or wheeze were present in 23 per cent of non-consulters, 27 per cent of average consulters and over 50 per cent of high consulters. Similarly, 48 per cent of the non-consulters smoked, drank heavily or were obese compared with 47 per cent of the average consulters and 61 per cent of the high consulters. The prevalence of recall of high blood pressure which had been diagnosed by a doctor rose from 6 per cent in non-consulters and 10 per cent in average consulters to 29 per cent in high consulters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Casual urine concentrations of sodium and potassium and geographic blood pressure variations in Great Britain.

The associations between blood pressure and urine sodium, potassium and creatinine have been studied among 1,240 men and 1,119 women living in nine British towns in order to assess the contribution of sodium and potassium intake to geographic BP variations within Great Britain. Significant positive associations were found between systolic BP and the urine sodium/potassium ratio for men (P less than 0.05) and for women (P less than 0.001), and for the sodium/creatinine ratio in men (P less than 0.01), after adjustment for age and body mass index. The findings for diastolic BP were similar, but non-significant for men. Associations between BP and sodium concentration were inconsistent and non-significant. The associations between BP and potassium concentration were consistently negative, and significant for diastolic in women (P less than 0.01). The correlations between the mean town systolic BPs and the sodium/potassium ratio were 0.65 (P = 0.058) for men, and 0.60 (P = 0.086) for women. Correlations for diastolic BP were such smaller. The association between BP and the sodium/potassium ratio in this study is consistent both within and between populations, although more so for women than for men. The results are also consistent with the results of other population studies using casual and 24 urine specimens. Although unable to quantify the effects of sodium and potassium with precision, the study suggests that the sodium/potassium ratio is of importance in geographic BP variations in Great Britain, at least for systolic blood pressure.

Adult↗