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Biomedical subjects

P Metcalf

Publications and source records attributed to P Metcalf.

At least 55 records · Page 3Linked to original sources

Health status and occupation: use of a health status index to measure the health of occupations.

A total of 4466 employed persons completed the short Auckland University Health Status Index (AUHSI) questionnaire and a health score was assigned to each individual on the basis of their responses. This health score was found to have statistically significant associations with a number of health-related measures, including socio-economic status (P < 0.001), and with occupational group: administrative, clerical/sales/service, skilled trades and unskilled labour (P < 0.001). Within the occupational groups, 3361 employees could be assigned to 42 specific occupations having 19 or more members each. After controlling for age and gender, significant differences in mean health score for specific occupation were found in the clerical/sales/service (P < 0.05), skilled trades (P = 0.002) and unskilled manual (P < 0.05) groups. It is postulated that these differences may be due to the nature of the specific occupation. Some possible reasons are listed. It is concluded that a global measure of health status such as this may be useful in the planning and evaluation of occupational health services.

Female↗

Serum 25-hydroxyvitamin D3 is related to physical activity and ethnicity but not obesity in a multicultural workforce.

BACKGROUND: Recent research suggests that body vitamin D levels are decreased in coronary heart disease and diabetes, but it is unclear which cardiovascular risk factors are related to vitamin D status. AIMS: To examine the relation between vitamin D status and major cardiovascular risk factors. METHODS: Serum 25-hydroxyvitamin D3, a marker of recent sun exposure and vitamin D status, was measured in 390 New Zealand residents (95 Pacific Islanders, 74 Maori and 221 others mostly of European descent), who were part of a larger cross-sectional survey of a workforce (n = 5677) aged 40-64 years. RESULTS: Serum 25-hydroxyvitamin D3 levels were significantly lower in Pacific Islanders (mean (SE) = 56 (3) nmol/L; p = 0.0001) and Maoris (68 (3) nmol/L; p = 0.036) compared with Europeans (75 (2) nmol/L) after adjusting for age, sex and time of year. Also adjusting for ethnic group, 25-hydroxyvitamin D3 was higher in people doing vigorous (aerobic) leisure physical activities (71 (2) nmol/L; p = 0.0066) and moderate (non-aerobic) activities (68 (3) nmol/L; p = 0.12) compared with those who were inactive (63 (2) nmol/L). However, 25-hydroxyvitamin D3 was unrelated to body mass index, serum lipids, blood pressure or cigarette smoking. CONCLUSIONS: People with increased skin pigmentation, such as Polynesians, and people who are inactive, have decreased body levels of vitamin D; this might partly explain their increased risk of cardiovascular disease.

Adult↗

Multiple functions of pro-parts of aspartic proteinase zymogens.

The importance of aspartic proteinases in human pathophysiology continues to initiate extensive research. With burgeoning information on their biological functions and structures, the traditional view of the role of activation peptides of aspartic proteinases solely as inhibitors of the active site is changing. These peptide segments, or pro-parts, are deemed important for correct folding, targeting, and control of the activation of aspartic proteinase zymogens. Consequently, the primary structures of pro-parts reflect these functions. We discuss guidelines for formation of hypotheses derived from comparing the physiological function of aspartic proteinases and sequences of their pro-parts.

Amino Acid Sequence↗

Hypertension and its treatment in a New Zealand multicultural workforce.

AIMS: To investigate ethnic variations in blood pressure levels and the likelihood of hypertension being treated in a multicultural New Zealand workforce. METHODS: An employed population of 5651 staff aged 40 to 64 years at worksites in Auckland and Tokoroa, who recorded their current prescribed medication, were measured for blood pressure, weight and height. Body mass index (BMI) was calculated. RESULTS: Mean blood pressure levels were higher in men than women, and increased with age and BMI. Compared with Europeans, mean systolic and diastolic blood pressures were higher in Maori (by 5 to 6 mmHg), Pacific Islanders (by 4 to 6 mmHg) and Asians (by 1 to 5 mmHg) after controlling for age and blood pressure treatment. This increase in Maori and Pacific Islanders, compared with Europeans, was approximately halved after also controlling for BMI, but still remained statistically significant (p < 0.05). In contrast, ethnic differences in BMI did not explain any of the blood pressure increase in Asians. In analyses restricted to hypertensive participants, the likelihood of hypertension being treated was higher in women than men (odds ratio (OR) = 3.42; 95% CI 2.13, 5.47), and lower in Maori (OR 0.33; 95% CI 0.19, 0.58), Pacific Islanders (OR 0.27; 95% CI 0.16, 0.47) and Asians (OR 0.29; 95% CI 0.10, 0.86) than Europeans. CONCLUSION: These results suggest that the likelihood of hypertension being treated is related to sex and ethnic group; and that other unknown factors, in addition to increased BMI levels, explain the higher blood pressure levels in Polynesians compared to Europeans.

Adult↗

Serum lipid levels in a New Zealand multicultural workforce.

AIMS: To examine ethnic variations in serum lipid levels and to determine whether lipids are related to lifestyle variables in a New Zealand multicultural workforce. METHODS: Fasting blood samples were collected from 5671 employed people for determination of serum total and HDL cholesterol, triglycerides, and LDL cholesterol. Individual exposures over the previous three months to smoking, alcohol, leisure time physical activity were recorded, and weight and height were measured to calculate body mass index (BMI). RESULTS: Maori and Pacific Islanders had lower age-adjusted total and LDL cholesterol levels than Europeans, and these differences were increased by controlling for BMI. In contrast, age-adjusted mean (SE) HDL cholesterol levels were also lower in Maori (men = 1.17 (0.02); women = 1.38 (0.03) mmol/L) and Pacific Islanders (men = 1.17 (0.01); women = 1.30 (0.02) mmol/L) compared with Europeans (men = 1.20 (0.01); women = 1.47 (0.01) mmol/L), but when BMI, smoking and other variables were controlled, levels were significantly higher in Maori and Pacific Islanders. With serum triglycerides, the pattern was not consistent in Maori and Pacific Islanders. Age-adjusted mean levels in Maori (men = 2.25 (0.07) mmol/L; women = 1.53(0.07) mmol/L) were significantly higher (p < 0.05) than in Pacific Islanders (men = 1.82 (0.06); women = 1.34(0.05) mmol/L) of the same sex. After controlling for BMI and other variables, triglyceride levels were also significantly lower in Pacific Islanders than in Europeans and Asians. BMI and smoking were positively associated with total and LDL cholesterol and triglycerides, and negatively with HDL cholesterol, after controlling for alcohol and physical activity. CONCLUSION: Lifestyle risk factors, particularly BMI and smoking, are strongly related to serum levels of all major lipids. Ethnic variations in coronary heart disease mortality rates in New Zealand are more consistent with ethnic variations in triglycerides than with variations in the other serum lipids.

Adult↗

Two crystal structures for cathepsin D: the lysosomal targeting signal and active site.

Two crystal structures are described for the lysosomal aspartic protease cathepsin D (EC 3.4.23.5). The molecular replacement method was used with X-ray diffraction data to 3 A resolution to produce structures for human spleen cathepsin D and for bovine liver cathepsin D complexed with the 6-peptide inhibitor pepstatin A. The lysosomal targeting region of cathepsin D defined by previous expression studies [Barnaski et al. (1990) Cell, 63, 281-219] is located in well defined electron density on the surface of the molecules. This region includes the putative binding site of the cis-Golgi phosphotransferase which is responsible for the initial sorting step for soluble proteins destined for lysosomes by phosphorylating the carbohydrates on these molecules. Carbohydrate density is visible at both expected positions on the cathepsin D molecules and, at the best defined position, four sugar residues extend towards the lysosomal targeting region. The active site of the protease and the active site cleft substrate binding subsites are described using the pepstatin inhibited structure. The model geometry for human cathepsin D has rms deviations from ideal of bonds and angles of 0.013 A and 3.2 degrees respectively. For bovine cathepsin D the corresponding figures are 0.014 A and 3.3 degrees. The crystallographic residuals (R factors) are 16.1% and 15.8% for the human and inhibited bovine cathepsin D models respectively. The free R factors, calculated with 10% of the data reserved for testing the models and not used for refinement, are 25.1% and 24.1% respectively.

Amino Acid Sequence↗

Diabetes mellitus and employment: survey of a New Zealand workforce.

A cross-sectional survey of a 5670 multiracial New Zealand workforce aged > 40 years was used to determine the health status of people with diabetes mellitus in employment. One hundred and two workers (73 men, 29 women) had known diabetes mellitus (prevalence of 1.8%) of whom 91 individuals (89.2%) had Type 2 diabetes. Mean age of diabetic workers was 51.1 +/- 5.6 (SD) years and median duration of disease was 5.0 (range 0-51) years. Most subjects were asymptomatic, although only 31.4% of diabetic workers had fasting glucose concentrations and 35.5% had fructosamine concentrations within the mean +/- 2SD range of a matched control group. Moreover, 22.5% of diabetic participants had fasting hypertriglyceridaemia and 21.6% had microalbuminuria. Ethnicity (non-European vs European) and lack of insulin therapy were the most important predictors of poor glycaemic control. We advocate more aggressive therapy with insulin and with culturally sensitive education programmes to avert long-term macrovascular complications.

Adult↗

Diabetes mellitus and employment: is there discrimination in the workplace?

The employment record of 102 diabetic workers (73 men, 29 women), identified in a cross-sectional survey of 5670 middle-aged people in a New Zealand workforce, was studied for evidence of discrimination in the workplace. Compared with 403 matched controls (292 men, 111 women), diabetic workers showed no significant differences in socioeconomic status, educational attainment, or distribution between occupational groups. Similarly, mean duration of current employment (12.3 vs 12.4 years), mean number of jobs in the past 5 years (1.25 vs 1.34 jobs), frequency of sickness absence, and mean number of hours worked each week (43.5 vs 43.3h) did not differ significantly between diabetic and non-diabetic groups. We found no significant differences in work stress, even among those diabetic individuals with poor blood glucose control. There was no convincing evidence across a broad spectrum of industry that diabetic workers did suffer discrimination in the workplace.

Absenteeism↗

Crystallization and initial crystallographic results for pepstatin A inhibited bovine cathepsin D.

Cathepsin D was purified from bovine liver by a method using two pepstatin A affinity columns. The eluted protein was combined with pepstatin A and the complex crystallized from 15% polyethylene glycol 8000 at pH 5.9. The crystals diffract to a resolution of 3.0 A and have space group P2(1)2(1)2(1) with unit cell dimensions a = 74.8 A, b = 76.0 A, c = 157.7 A. There are two molecules in the asymmetric unit. The structure was solved by molecular replacement using a pepsin search model and both molecules showed clearly interpretable density in the position expected for pepstatin A in a preliminary difference map. The refined model has r.m.s. deviations from ideal bond lengths and angles of 0.014 A and 3.2 degrees, respectively, and a crystallographic R factor of 17%.

Animals↗

Purification and crystallization of human cathepsin D.

The two-chain form of human cathepsin D was purified from human spleen with a method utilizing an ion exchange chromatography step prior to the pepstatin affinity column normally used to purify aspartic proteases. The protein was crystallized from 21% polyethylene glycol 8000 at pH 4.0 using the hanging drop vapour diffusion method. Small crystals were used as seeds to grow crystals suitable for X-ray data collection. The crystals diffract to a resolution of 3.2 A and have space group P2(1)2(1)2(1) with unit cell dimensions a = 59.9 A, b = 99.6 A, c = 133.6 A. There are two molecules in the asymmetric unit.

Cathepsin D↗

The relationship between body mass index and socioeconomic status in New Zealand: ethnic and occupational factors.

AIMS: the relationship between body mass index (BMI) and socioeconomic status (SES) was examined in a multiracial New Zealand workforce in order to investigate ethnic variations. METHODS: an employed population of 5673 people were measured for weight and height and BMI calculated. Socioeconomic status was assigned using the UK Registrar General's scale. RESULTS: both European women and men showed an inverse relationship of increasing BMI with decreasing SES which is typical of developed societies. Maori, Pacific Islanders and Asians did not, but neither did they show the direct relationship of developing societies. Examination of the components of SES showed that combined family income did not influence BMI in any ethnic group but that education was strongly associated with BMI in Europeans (p = 0.0001) and weakly associated in Maori (p = 0.0603), and occupation was strongly associated with BMI in Europeans (p = 0.0001) and weakly associated in Pacific Islanders (p = 0.0148) independently of education. CONCLUSIONS: ethnic variations are partly explained by educational levels and occupation, but not by income. Increased education may decrease prevalence of obesity. Some occupational factors are discussed.

Adult↗