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Biomedical subjects

P Metcalf

Publications and source records attributed to P Metcalf.

At least 37 records · Page 2Linked to original sources
PubMed1997

Risk factors differ for carotid artery plaque with and without acoustic shadowing. Atherosclerosis Risk in Communities Study Investigators.

To investigate the association of gender, ethnicity, and several cardiovascular risk factors with carotid artery plaque and plaque with acoustic shadowing in a population-based sample, high-resolution B-mode ultrasonography was used to characterize lesions in the common and internal carotid arteries, and at the carotid bifurcation in 12,796 US men and women, aged 45 to 64 years, participating in the Atherosclerosis Risk in Communities Study (ARIC) baseline survey. In multiple logistic regression analyses, male gender (odds ratio and 95% confidence interval: 1.52 [1.39-1.67]) and increased total (1.47 [1.32-1.63]) and low-density-lipoprotein cholesterol (1.49 [1.34-1.65]) levels were statistically significantly associated only with the presence of plaque. In contradistinction, smoking (2.22 [1.79-2.75]) and hypertension (1.54 [1.30-1.82]) were additionally associated with acoustic shadowing. Hyperfibrinogenemia (1.33 [1.12-1.59]) was associated only with lesions accompanied by acoustic shadowing. While ethnicity associations with plaque alone varied across the artery segments, among those with plaque, being white was uniformly associated with acoustic shadowing. After multivariable adjustment, high-density-lipoprotein cholesterol was not associated with either manifestation of atherosclerosis. In conclusion, differences were seen in the associations of established cardiovascular risk factors with discretely characterized carotid artery plaque lesions, according to the presence or absence of acoustic shadowing suggestive of mineralization of plaque.

Carotid Artery, Common↗
PubMed1996

Crystallization of DsbC, the disulfide bond isomerase of Escherichia coli.

DsbC is a 2 x 23 kDa soluble dimeric protein molecule involved in protein disulfide bond formation in the E. coli periplasm, primarily catalyzing disulfide bond rearrangements. Crystals of both the native and selenomethione protein suitable for structure determination were obtained using the hanging-drop vapour-diffusion method. The best crystals were obtained using 18-22% (v/v) polyethylene glycol 550 monomethyl ether in 100 mM Tris-HCl (pH 8.9). Seeding methods were used to produce large crystals diffracting to 2 A resolution, and the detergent n-octyl-beta-glucoside was used to improve crystal quality. Significant variation in cell dimensions and crystal order was observed. Cell dimensions obtained for frozen crystals were in the range a = 58.8 (0.3), b = 78.9 (0.5), c = 95.2 (5.0) A. The lattice is orthorhombic and systematic absences indicate that the space group is P2(1)2(1)2(1).

Journal Article↗
PubMed1996

Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population. Atherosclerosis Risk in Communities Study Investigators.

Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P < .001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P < .001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P < .001 for most) and of body mass index (1.6 to 4.5, P < .05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults.

Cluster Analysis↗
PubMed1996

Prevalence of Helicobacter pylori infection in different ethnic groups in New Zealand children and adults.

BACKGROUND: Helicobacter pylori infection is a major risk factor for peptic ulcer disease and gastric cancer. A study of patients with dyspepsia attending for gastroscopy showed significant differences in H. pylori seropositivity between ethnic groups. AIMS: To determine the prevalence of H. pylori in children and adults in the community in different ethnic groups and to identify risk factors for infection. METHODS: Serum samples (324) were randomly selected from a cross-sectional survey of 11-12 year old school children with a high proportion of Maori and Pacific Island groups. Serum samples (579) were randomly selected from a cross-sectional workforce survey of 5677 participants aged 40-64 years. Serum samples were tested for H.pylori IgG. RESULTS: The percentage seropositivity in 11-12 year old children was European 7%, Maori/part Maori 21%, all Pacific Island groups 48% and for the workforce survey 35.8%, 57.4% and 73.2% respectively. Compared with Europeans the increased relative risk of seropositivity for H.pylori in Maori and Pacific Island participants was significant after adjusting for age and socio-economic status (1.43 [1.13, 1.80] and 1.76 [1.43, 2.18]) respectively. The relative risk of H.pylori infection significantly increased with age, lower socio-economic status and lower household income, but was not significantly associated with gender, alcohol or cigarette use. CONCLUSIONS: The high seroprevalence of H.pylori in Maori and Pacific Island groups is consistent with the differences in incidence of gastric cancer. H.pylori continues to be a common infection in Maori and Pacific Island school children. Ethnicity appears to be a risk factor for H.pylori independent of socio-economic status.

Adult↗
PubMed1995

Crystallization and preliminary X-ray diffraction studies of leishmanolysin, the major surface metalloproteinase from Leishmania major.

The membrane-bound GPI-anchored zinc metalloproteinase leishmanolysin purified from Leishmania major promastigotes has been crystallized in its mature form. Two crystal forms of leishmanolysin have been grown by the vapor diffusion method using 2-methyl-2,4-pentanediol as the precipitant. Macroseeding techniques were employed to produce large single crystals. Protein microheterogeneity in molecular size and charge was incorporated into both crystal forms. The tetragonal crystal form belongs to the space group P4(1)2(1)2 or the enantiomorph P4(3)2(1)2, has unit cell parameters of a = b = 63.6 A, c = 251.4 A, and contains one molecule per asymmetric unit. The second crystal form is monoclinic, space group C2, with unit cell dimensions a = 107.2 A, b = 90.6 A, c = 70.6 A, beta = 110.6 degrees, and also contains one molecule per asymmetric unit. Both crystal forms diffract X-rays beyond 2.6 A resolution and are suitable for X-ray analysis. Native diffraction data sets have been collected and the structure determination of leishmanolysin using a combination of the isomorphous replacement and the molecular replacement methods is in progress.

Animals↗
PubMed1995

Human procathepsin D: three-dimensional model and isolation.

Human procathepsin D was isolated from medium of human breast cancer cell line ZR-75-1 potentiated with estrogen. The isolation involved both immunoaffinity chromatography and ion-exchange chromatography. The affinity chromatography employed polyclonal antibodies raised against a synthetic activation peptide of human cathepsin D. We have started preliminary crystallization trials using the isolated material. A model of human procathepsin D was also built using coordinates of human cathepsin D and pig pepsinogen. The model aids understanding of multiple roles played by activation peptides of aspartic proteinases and will be used as a starting model for molecular replacement.

Amino Acid Sequence↗
PubMed1995

Serum 25-hydroxyvitamin D3 levels decreased in impaired glucose tolerance and diabetes mellitus.

A cross-sectional survey was carried out in a New Zealand Polynesian and Caucasian workforce of 5677 staff aged 40-64 years to determine whether serum concentrations of 25-hydroxyvitamin D3 are altered in people with newly diagnosed diabetes mellitus and impaired glucose tolerance (IGT). Serum 25-hydroxyvitamin D3 concentration was significantly lower in newly detected cases with diabetes and IGT (n = 238) compared with controls individually matched by sex, age (+/- 2 years), ethnicity, and date of interview (mean (S.D.): 69 (31) vs. 76 (34) nmol/l; P = 0.0016). Among controls, serum concentrations were significantly lower in Maori (mean (S.E.) = 65 (5) nmol/l; P = 0.0013) and Pacific Islanders (59 (4) nmol/l; P = 0.0001) compared with Europeans (82 (3) nmol/l), after adjusting for age, sex, and time of year. We conclude that diabetes and IGT are associated with low serum concentrations of 25-hydroxyvitamin D3 and that low concentrations of this hormone in New Zealand Polynesians may partly explain their increased prevalence of diabetes/IGT compared with Europeans.

Adult↗
PubMed1995

Serum 25-hydroxycholecalciferol concentration in newly detected hypertension.

Although blood concentrations of the active metabolite 1,25-dihydroxyvitamin D are raised in hypertension, concentrations of 25-hydroxyvitamin D, the main vitamin D metabolite, do not appear to have been reported in newly detected hypertension. Serum levels of 25-hydroxycholecalciferol were measured in 186 newly detected hypertensive patients (blood pressure > 160/95 mm Hg and never on antihypertensive medication) and normotensive controls individually matched by sex, age (+/- 2 years), ethnicity, and date of interview. Serum 25-hydroxycholecalciferol levels were similar in cases (mean (SD) = 64 (21) nmol/L) and controls (67 (28) nmol/L, P = .20). We conclude that serum 25-hydroxycholecalciferol, a marker of body vitamin D, is normal in hypertension.

Age Factors↗