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Biomedical subjects

P J Park

Publications and source records attributed to P J Park.

7 recordsLinked to original sources

The performance of a risk score in predicting undiagnosed hyperglycemia.

OBJECTIVE: Type 2 diabetes is a serious disease that is commonly undetected and for which screening is sometimes advocated. A number of risk factors are associated with prevalent undiagnosed diabetes. The use of routinely available information on these factors has been proposed as a simple and effective way of identifying individuals at high risk for having the disease. The objective of this study was to assess the effectiveness of the Cambridge risk score in a large and representative population. RESEARCH DESIGN AND METHODS: A risk score derived from data in a previous study was tested for its ability to detect prevalent undiagnosed hyperglycemia as measured by a GHb > or = 6.0, 6.5, or 7% in 6,567 subjects aged 39-78 years in the European Prospective Investigation of Cancer-Norfolk cohort. RESULTS: For a specificity of 78%, the risk score predicted a GHb of > or = 7.0% in subjects aged 39-78 years, with a sensitivity of 51% (95% CI 40-62). The areas under the receiver-operating characteristic (ROC) curve for GHb > or = 6.0, 6.5, and 7% were 65.7% (63.8-67.6), 71.2% (68.4-75.2), and 74.2% (69.5-79.0), respectively. The area under the ROC curve was not significantly reduced if data on family and smoking history were unavailable for any of the cut-offs for GHb. CONCLUSIONS: The risk score performed as well as other previously reported models in all age groups. We concluded that a simple risk score using data routinely available in primary care can identify people with an elevated GHb with reasonable sensitivity and specificity, and it could therefore form part of a strategy for early detection of type 2 diabetes.

Adult↗

Angiotensin I converting enzyme inhibitory peptides purified from bovine skin gelatin hydrolysate.

Bovine skin gelatin was hydrolyzed with sequential protease treatments in the order of Alcalase, Pronase E, and collagenase using a three-step ultrafiltration membrane reactor. The molecular weight distributions of the first, second, and third hydrolysates were 4.8-6.6, 3.4-6.6, and 0.9-1.9 kDa, respectively. The angiotensin I converting enzyme (ACE) inhibitory activity of the third hydrolysate (IC(50) = 0.689 mg/mL) was higher than that of the first and second hydrolysates. Two different peptides showing strong ACE inhibitory activity were isolated from the hydrolysate using consecutive chromatographic methods including gel filtration chromatography, ion-exchange chromatography, and reversed-phase high-performance liquid chromatography. The isolated peptides were composed of Gly-Pro-Leu and Gly-Pro-Val and showed IC(50) values of 2.55 and 4.67 microM, respectively.

Angiotensin-Converting Enzyme Inhibitors↗

Subacute toxicity of chitosan oligosaccharide in Sprague-Dawley rats.

A subacute oral toxicity study of chitosan oligosaccharide was performed in Sprague-Dawley rats of both sexes. Each 36 male and female rats were administered by gavage with 500, 1,000 and 2,000 mg/kg/day for 4 weeks (7 days/week), respectively. Examinations regarding clinical signs, body weights, hematological and biochemical parameters, and histopathological examinations were carried out. There were no significant differences in behavior or external appearance, body weight and food consumption between control and treated rats. In addition, no significant differences in urinalysis, hematology, blood biochemistry, relative organ weights and histopathological findings were found in both control and treated rats. In conclusion, it was suggested that subacute toxicity of chitosan oligosaccharide was low and the no-observed adverse effect level was considered to be over 2,000 mg/kg in rats.

Animals↗

A nonparametric scoring algorithm for identifying informative genes from microarray data.

Microarray data routinely contain gene expression levels of thousands of genes. In the context of medical diagnostics, an important problem is to find the genes that are correlated with given phenotypes. These genes may reveal insights to biological processes and may be used to predict the phenotypes of new samples. In most cases, while the gene expression levels are available for a large number of genes, only a small fraction of these genes may be informative in classification with statistical significance. We introduce a nonparametric scoring algorithm that assigns a score to each gene based on samples with known classes. Based on these scores, we can find a small set of genes which are informative of their class, and subsequent analysis can be carried out with this set. This procedure is robust to outliers and different normalization schemes, and immediately reduces the size of the data with little loss of information. We study the properties of this algorithm and apply it to the data set from cancer patients. We quantify the information in a given set of genes by comparing its distribution of the score statistics to a set of distributions generated by permutations that preserve the correlation structure among the genes.

Algorithms↗

Terminal glycosylation of cystic fibrosis airway epithelial cells.

Cystic fibrosis (CF) has a characteristic glycosylation phenotype usually expressed as a decreased ratio of sialic acid to fucose. The glycosylation phenotype was found in CF/T1 airway epithelial cells (deltaF508/deltaF508). When these cells were transfected and were expressing high amounts of wtCFTR, as detected by Western blot analysis and in situ hybridization, the cell membrane glycoconjugates had an increased sialic acid content and decreased fucosyl residues in alpha1,3/4 linkage to antennary N-acetyl glucosamine (Fuc(alpha)1,3/4GlcNAc). After the expression of wtCFTR decreased, the amount of sialic acid and Fuc(alpha)1,3/4GlcNAc returned to levels shown by the parent CF cells. Sialic acid was measured by chemical analysis and Fuc(alpha)1,3/4GlcNAc was detected with a specific alpha1,3/4 fucosidase. CF and non-CF airway cells in primary culture also had a similar reciprocal relationship between fucosylation and sialylation. It is possible that the glycosylation phenotype is involved in the pathogenesis of CF lung disease by facilitating bacterial colonization and leukocyte recruitment.

Cell Membrane↗

The effect of varying the screening interval on false positives and duration of undiagnosed disease in a screening programme for type 2 diabetes.

OBJECTIVES: The aims of this study were to quantify the proportion of people diagnosed as having type 2 diabetes by standard 75 g oral glucose tolerance test, in a hypothetical screening programme, who would actually be false positives (false positive percentage), and the effect on the false positive percentage of varying the time between repeat screens. We also calculated the duration in person years of exposure to undiagnosed disease in the population for each screening interval. SETTING: Ely, Cambridgeshire, UK. METHODS: We used the glucose tolerance data from 965 participants of the Ely Diabetes Project, who were tested 4.5 years apart, to calculate the population's between and within person variance for 2 hour plasma glucose, and constructed a probability matrix of observed v true glucose tolerance categories. The progression of the population between glucose tolerance categories was modelled assuming exponential times to progression. RESULTS: After one year, 47.5% of test positives were disease free: almost half of those labelled with diabetes would not have the disease. For a 5 year interval, the false positive percentage was 27.6%, but the population would have been exposed to undiagnosed diabetes for 144 person years. CONCLUSIONS: Screening can be associated with both benefit and harm; the balance is dependent on characteristics of the disease and the screening programme. This study has quantified the trade off between exposure to undiagnosed diabetes and false positive results to inform the debate about screening for type 2 diabetes.

Blood Glucose↗

Dynamics of pore growth in membranes and membrane stability.

Pores can form and grow in biomembranes because of factors such as thermal fluctuation, transmembrane electrical potential, and cellular environment. We propose a new statistical physics model of the pore growth treated as a non-Markovian stochastic process, with a free energy barrier and memory friction from the membrane matrix treated as a quasi-two-dimensional viscoelastic and dielectric fluid continuum. On the basis of the modern theory of activated barrier crossing, an analytical expression for membrane lifetime and the phase diagram for membrane stability are obtained. The memory effect due to membrane viscoelasticity and the elasticity due to cytoskeletal network are found to induce sharp transitions to membrane stability against pore growth and compete with other factors to manifest rich dynamic transitions over the membrane lifetime.

Biophysical Phenomena↗