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P Metcalf

Publications and source records attributed to P Metcalf.

At least 73 records · Page 4Linked to original sources

Three-dimensional structure of Gln25-ribonuclease T1 at 1.84-A resolution: structural variations at the base recognition and catalytic sites.

The structure of the Gln25 variant of ribonuclease T1 (RNase T1) crystallized at pH 7 and at high ionic strength has been solved by molecular replacement using the coordinates of the Lys25-RNase T1/2'-guanylic acid (2'GMP) complex at pH 5 [Arni et al. (1988) J. Biol. Chem. 263, 15358-15368] and refined by energy minimization and stereochemically restrained least-squares minimization to a crystallographic R-factor of 14.4% at 1.84-A resolution. The asymmetric unit contains three molecules, and the final model consists of 2302 protein atoms, 3 sulfates (at the catalytic sites), and 179 solvent water molecules. The estimated root mean square (rms) error in the coordinates is 0.15 A, and the rms deviation from ideality is 0.018 A for bond lengths and 1.8 degrees for bond angles. Significant differences are observed between the three molecules in the asymmetric unit at the base recognition and catalytic sites.

Amino Acid Sequence↗

Albuminuria in people at least 40 years old: effect of obesity, hypertension, and hyperlipidemia.

Concentrations of urinary albumin and the albumin:creatinine ratio were measured in early-morning urine specimens from 5670 people older than 40 years who participated in a health screening survey of a local workforce. Sex-specific reference intervals were determined in a subgroup of 3597 people after excluding 2073 individuals with Albustix-positive proteinuria; diabetes mellitus; bacteriuria; current hypertension; body mass index greater than or equal to 30 kg/m2; or serum triglyceride greater than or equal to 2.5 mmol/L. The 97.5 percentile concentration for urinary albumin was 28 mg/L in men and 29 mg/L in women; for the albumin:creatinine ratio this was 2.3 g/mol in men and 2.8 g/mol in women. In the study population, the degree of albuminuria showed piecewise log-linear relationships with diastolic blood pressure (P = 0.0001) and body mass index (P = 0.0001), log-linear relationships with hypertriglyceridemia (P = 0.0001) and hypercholesterolemia (P = 0.0001), and a negative piecewise linear relationship with high-density lipoprotein (HDL) cholesterol (P = 0.0461).

Adult↗

Prevalence of diabetes mellitus and impaired glucose tolerance in a New Zealand multiracial workforce.

A cross sectional survey was carried out among a multiracial workforce of 5677 staff aged 40 to 64 years at worksites in Auckland and Tokoroa to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT). The prevalences of diabetes mellitus and IGT were both similar for men and women, but increased with age. The relative risks for diabetes mellitus and for IGT were both inversely associated with gross annual household income, independent of age and ethnicity, being 1.61 (95% Cl = 1.10, 2.37) and 1.80 (95% Cl = 1.21, 2.67) respectively, in the lowest income group (less than $30,000) compared with the highest (greater than $40,000). Compared with Europeans, the relative risk of diabetes mellitus was significantly increased among Maori (3.63; 95% Cl = 2.48, 5.32), Pacific Islanders (2.34; 95% Cl = 1.50, 3.66) and Asians (5.97; 95% Cl = 2.61, 13.65), after controlling for age, income and body mass index. The increased prevalence of diabetes mellitus among Maori and Pacific Islanders, but not in Asians, could be partly attributed to their increased levels of obesity compared with Europeans. However, other factors, in addition to obesity, explain the increased diabetes prevalence in nonEuropean groups.

Adult↗

The three-dimensional structure of reovirus obtained by cryo-electron microscopy.

The structures of reovirus serotypes T2J (Jones), T3D (Dearing) and the T3D core particle have been determined by cryo-electron microscopy and image processing. At a resolution of 30 A the two serotypes have similar features. The core is visible within the virus structure. The outer surface of the virus particles contains 120 holes at T = 13.1 local 6-fold axes. The holes penetrate into the virus as far as the surface of the internal core shell. Protrusions extending 4 nm from the virus surface surround each hole on the outside of the virus. At the 5-fold axes on the surface of the virus flat 'penton craters' form covers over the underlying core spikes. The detailed structure of the reovirus shell is very different to that of rotavirus although both have holes at T = 13.1 axes. Little evidence was seen of reovirus fibres extending from the virus surface.

Image Processing, Computer-Assisted↗

Fructosamine Test-Plus, a modified fructosamine assay evaluated.

We have evaluated Fructosamine Test-Plus, a commercial fructosamine assay based on the reduction of nitro-blue tetrazolium dye in alkaline buffer (Clin Chem 1985;31:1550-4), modified by including a detergent and uricase in the reagent, by changing the concentrations of buffer and dye, and by changing the approach to primary calibration. Specimens were from 2321 participants in a health screening survey in a local workforce. Compared with the original fructosamine method, the Fructosamine Test-Plus method was less affected by protein concentration in the sample and less subject to interference from hyperlipidemia. The changes have also extended the linearity of the assay in the pathological range. However, as a screening method for diabetes mellitus in a population with a disease prevalence of 2.28%, the performance of Fructosamine Test-Plus was similar to the original assay.

Adult↗

Factors associated with development of diabetes mellitus: results from a cross sectional survey in Kawerau.

To determine risk factors for diabetes mellitus, a cross sectional study was performed on adult residents of Kawerau. Three thousand nine hundred and eighty-two adults (82.8% response rate) had a fructosamine screening test and undiagnosed diabetes was confirmed in 29 cases. Controls were 241 nondiabetic individuals randomly selected from residents with normal fructosamine result. Compared with controls, new diabetics were significantly older and more obese (p less than 0.05). After controlling for age and body mass index, we also found significant increases in systolic and diastolic blood pressure, 2 hour insulin, and fasting triglyceride levels. These results suggest that the above variables are associated with diabetes mellitus independent of age and obesity.

Alcohol Drinking↗

Fructosamine compared with a glucose load as a screening test for gestational diabetes.

Five hundred seven women were screened for gestational diabetes between 20-36 weeks' gestation. All received a 100-g glucose (polycose) load at 28 weeks with measurement of plasma glucose 1 hour later. Fructosamine levels were measured at 4-week intervals from 20-36 weeks. At 36 weeks, a full 100-g 3-hour glucose tolerance test was performed on all subjects. Eighteen women were diagnosed as having gestational diabetes. The glucose load had a sensitivity of 81% in detection of gestational diabetes, compared with 50% for fructosamine at 36 weeks. Fructosamine is not useful as a screening test for gestational diabetes as currently defined.

Diabetes Mellitus↗

Crystallization of amino-terminal domains and domain fragments of variant surface glycoproteins from Trypanosoma brucei brucei.

Crystals were produced from variant surface glycoproteins (VSG) of Trypanosoma brucei brucei antigenic variants MITat 1.2, 1.6, and ILTat 1.22, 1.23, 1.24, 1.25, and 1.26. Purified VSGs had molecular weights from 60,000 to 68,000 on sodium dodecyl sulfate-polyacrylamide gels, whereas the crystals obtained were composed of polypeptides of approximate Mr 40,000-50,000. Amino-terminal amino acid sequences determined from the crystallized VSGs were identical to sequences obtained from the respective intact proteins, indicating that the crystals contained VSG amino-terminal fragments. Crystallization conditions and lattice dimensions of the crystals are given.

Animals↗

Fructosamine concentrations in general population of Kawerau.

We measured fructosamine concentrations in nonfasted serum from 7094 residents (82.8% of the estimated population) of Kawerau, New Zealand, including 65 known diabetic patients (prevalence of 0.92%). Fructosamine results showed a trimodal frequency distribution, with cutting points corresponding to 5th and 95th percentile values. Forty-two diabetic individuals had levels that exceeded the 95th percentile. These individuals had more severe metabolic abnormalities, characterized by lower plasma C-peptide and elevated fasting plasma glucose concentrations. Mean fructosamine values also showed a significant increase with age and a highly significant age-ethnic interaction that paralleled the higher frequency of diabetes in older age groups and among elderly Maori people. However, as a screening method in the general population, fructosamine measurement was diagnostically deficient because of a weak correlation with serum albumin. Arithmetic correction for albumin concentration in the sample did not increase the diagnostic usefulness of the test.

Adult↗

Serum fructosamine as a screening method for diabetes mellitus in patients with suspected acute myocardial infarction.

It is important to identify diabetic patients in a coronary care population because they have a higher risk of suffering congestive heart failure, dysrhythmias and death following myocardial infarction. In order to determine the most efficient screening method for diabetes, we compared fructosamine and glucose measurements on admission blood specimens from 256 consecutive patients. Of 15 (5.9%) known diabetic patients, 12 had glucose results greater than or equal to 7.8 mmol/l and nine had fructosamine levels greater than 2.87 mmol/l. However, elevated glucose results were also found in a high proportion (49.2%) of patients with no previous history of diabetes. We performed glucose tolerance tests in 107 patients after discharge to determine the frequency of false-positive observations. Fructosamine yielded five (4.6%) false-positive results, whereas plasma glucose yielded 47 (43.9%) false-positive observations. We conclude that serum fructosamine provides a more specific screening method for diabetes in this population because the results are unaffected by stress hyperglycemia.

Adult↗

Protein, DNA, and virus crystallography with a focused imaging proportional counter.

A set of programs has been developed for rapid collection of x-ray intensity data from protein and virus crystals with a commercially available two-dimensional focused geometry electronic detector. The detector is compact and portable, with unusually high spatial resolution comparable to that used in oscillation photography. It has allowed x-ray data collection on weakly diffracting crystals with large unit cells, as well as more conventional "diffractometer-quality" crystals. The quality of the data is compared with that from oscillation photography and automated diffractometry in the range of unit cells from 96.3 to 383.2 angstroms. Isomorphous and anomalous difference Pattersons, based on detector data, are shown for a variable surface glycoprotein mercury derivative and for a repressor-DNA bromine derivative, which has been solved at 7 angstroms with detector data only.

Computers↗

Quality assessment of determinations of serum fructosamine in 33 clinical chemistry laboratories.

We investigated the analytical performance of fructosamine measurement in 33 routine clinical chemistry laboratories. We prepared 12 human control sera spanning a range of nondiabetic and diabetic fructosamine concentrations and assigned target values by using commercial reagents and a Cobas Bio centrifugal analyzer. Each control serum was analyzed by participating laboratories on two separate occasions. Averaged results were compared with target values, and systematic error was determined from slope and intercept regression coefficients. Overall, we found no significant (p greater than 0.05) slope or intercept bias, although slight nonlinearity was found with bichromatic instruments. Random error was determined from the standard error of estimate and from duplicate measurements. We found a median interlaboratory CV of 5.36% and similar analytical performance with all automated instruments used. The median random error with manual techniques was 18.1%. We conclude that fructosamine measurement as currently performed in routine laboratories is sufficiently accurate and reliable to function as an index of blood glucose control in diabetic patients.

Blood Glucose↗

Aerial spraying of 2,4,5-T and human birth malformations: an epidemiological investigation.

An investigation of the rate of birth malformations in the Northland region of New Zealand provides no evidence to associate spraying of 2,4,5-trichlorophenoxyacetic acid with the occurrence of any malformation of the central nervous system, including spina bifida. A statistically significant association between spray and malformation is found in the case of talipes. Whether this association indicates a causal relation remains to be established.

2,4,5-Trichlorophenoxyacetic Acid↗

Congenital malformations in the newborn in Northland: 1966-1977.

A survey of all hospital births in the Northland region of New Zealand during 1966-1977 has been carried out. There were 23 591 births during this period, of which 374 had significant malformations diagnosed in hospital. There were 243 stillbirths, 148 neonatal deaths; 334 infants with diagnosed malformations survived to discharge. Rates of stillbirth, neonatal death and malformation were higher amongst Maoris than amongst non-Maoris. The commoner malformations (with incidence rates per thousand births) were: talipes (5.2), spina bifida, congenital heart defects, cleft lip and/or cleft palate (1.5), and anencephalus (1.0). Anencephalus was commoner amongst females than males; talipes and isolated cleft palate were commoner amongst Maoris, anencephalus and spina bifida amongst non-Maoris. There is some evidence that whereas the rate of stillbirth has declined over the period, the rate of neonatal death has risen.

Congenital Abnormalities↗