Biomedical subjects

Jong Park

Publications and source records attributed to Jong Park.

11 recordsLinked to original sources

PubMed2005

Relations of plasma high-sensitivity C-reactive protein to various cardiovascular risk factors.

This study was performed to evaluate the relation of high-sensitivity C-reactive protein (hsCRP) with several cardiovascular risk factors such as age, blood pressure, smoking habit and serum lipids, body mass index, blood glucose, regular exercise, alcohol drinking, white blood cell counts in a cross-sectional survey. Plasma hsCRP was measured by immunoturbidimetry in 202 subjects, aged over 50 yr, who participated in health-check survey in a rural area of Jeollanamdo, Korea. Plasma hsCRP level was 1.9 +/- 3.0 mg/dL. There were significant associations between hsCRP levels and age, white blood cell counts, blood glucose, diastolic blood pressure, HDL-cholesterol, body mass index and smoking status. In stepwise multivariate regression analysis, white blood cell counts, age, blood glucose, smoking status and body mass index were independent correlates of hsCRP levels. In conclusion, plasma hsCRP levels were associated with several cardiovascular risk factors, and these data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease. Further what we need now are prospective studies to evaluate the association of C-reactive protein concentrations with subsequent cardiac events.

Alcohol Drinking↗

PubMed2004

Using convex hulls to extract interaction interfaces from known structures.

MOTIVATION: Protein interactions provide an important context for the understanding of function. Experimental approaches have been complemented with computational ones, such as PSIMAP, which computes domain-domain interactions for all multi-domain and multi-chain proteins in the Protein Data Bank (PDB). PSIMAP has been used to determine that superfamilies occurring in many species have many interaction partners, to show examples of convergent evolution through shared interaction partners and to uncover complexes in the interaction map. To determine an interaction, the original PSIMAP algorithm checks all residue pairs of any domain pair defined by classification systems such as SCOP. The computation takes several days for the PDB. The computation of PSIMAP has two shortcomings: first, the original PSIMAP algorithm considers only interactions of residue pairs rather than atom pairs losing information for detailed analysis of contact patterns. At the atomic level the original algorithm would take months. Second, with the superlinear growth of PDB, PSIMAP is not sustainable. RESULTS: We address these two shortcomings by developing a family of new algorithms for the computation of domain-domain interactions based on the idea of bounding shapes, which are used to prune the search space. The best of the algorithms improves on the old PSIMAP algorithm by a factor of 60 on the PDB. Additionally, the algorithms allow a distributed computation, which we carry out on a farm of 80 Linux PCs. Overall, the new algorithms reduce the computation at atomic level from months to 20 min. The combination of pruning and distribution makes the new algorithm scalable and sustainable even with the superlinear growth in PDB.

Algorithms↗

PubMed2004

HPID: the Human Protein Interaction Database.

UNLABELLED: The Human Protein Interaction Database (http://www.hpid.org) was designed (1) to provide human protein interaction information pre-computed from existing structural and experimental data, (2) to predict potential interactions between proteins submitted by users and (3) to provide a depository for new human protein interaction data from users. Two types of interaction are available from the pre-computed data: (1) interactions at the protein superfamily level and (2) those transferred from the interactions of yeast proteins. Interactions at the superfamily level were obtained by locating known structural interactions of the PDB in the SCOP domains and identifying homologs of the domains in the human proteins. Interactions transferred from yeast proteins were obtained by identifying homologs of the yeast proteins in the human proteins. For each human protein in the database and each query submitted by users, the protein superfamilies and yeast proteins assigned to the protein are shown, along with their interacting partners. We have also developed a set of web-based programs so that users can visualize and analyze protein interaction networks in order to explore the networks further. AVAILABILITY: http://www.hpid.org.

Algorithms↗

PubMed2004

Enhanced protein glutathiolation and oxidative stress in cigarette smokers.

There are many functional assays of oxidative damage to DNA, protein, and lipids but few reliable markers of chronic oxidative stress. The glutathiolation of proteins at key Cys residues is considered an important redox-sensitive, posttranslational signaling mechanism in the regulation of critical cellular functions. To determine whether protein bound glutathione (GSSP) is a sensitive indicator of oxidative stress, red blood cell and plasma concentrations were measured and compared between smokers and nonsmokers. In a community-based study conducted in Westchester County, New York, USA, blood samples were obtained from 354 cigarette smokers and 97 never smokers. The mean concentration of blood GSSP (micromol/L) was 32% higher in cigarette smokers and 43% higher when standardized by hemoglobin concentrations (p <.01). Plasma GSSP levels were also 20% higher in smokers than in nonsmokers (p <.001). The relationship was dose-dependent, with blood GSSP levels significantly correlated with cigarettes smoked per day, plasma cotinine, and plasma thiocyanate (r values ranged from .25 to .40). In smokers, there were no significant differences in GSSP and GSH levels by GSTM1 or GSTM3 genotype. Intraindividual variation in blood samples, as determined by taking serial samples over a 2-week period, was low (CV = 12.1%, n = 8). GSSP levels are stable over time but increase in response to the abundant free radicals in cigarette smoke. These findings support the use of GSSP as a sensitive biomarker of oxidative stress.

Blood Proteins↗

PubMed2004

The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk.

OBJECTIVE: The human 8-oxoguanine DNA N-glycosylase 1 gene encodes a DNA glycosylase that is involved in the base excision repair of 8-hydroxy-2-deoxyguanine from oxidatively-damaged DNA and expressed in lung tissue. The codon 326 polymorphism in the hOGG1 gene has been suggested to reduce DNA repair enzyme activity based on in vitro functional analysis. The goal of the present study is to determine whether the codon 326 polymorphism was significantly associated with alterations in individual risk for lung cancer. METHODS: To determine whether hOGG1 plays a role in risk for lung cancer, we measured the prevalence of the Ser326Cys polymorphism in incident lung cancer patients and matched non-cancer controls. hOGG1 genotyping was performed by PCR-restriction fragment length polymorphism analysis of genomic DNA isolated from 179 Caucasian lung cancer cases and 358 controls individually matched in a 1:2 ratio by race-, sex- and age (+/- 5 years). RESULTS: Significantly increased risk for lung cancer was observed for both the hOGG1 326 (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.2-2.9) and hOGG1 326 genotypes (OR = 3.8, 95% CI = 1.4-10.6). The increased risk for lung cancer was observed for subjects with both the hOGG1 326 (OR = 1.7, 95% CI = 1.1-2.8) and hOGG1 326 genotypes (OR = 4.9, 95% CI = 1.5-16.1) in ever-smokers. A significant association was found between hOGG1 genotypes and lung cancer risk with a dose-dependent effect with smoking. Significantly increased risk for variant hOGG1 genotypes was observed for all non-small cell lung cancer patients. CONCLUSION: These results suggest that the hOGG1 Ser326Cys polymorphism plays an important role in the risk for lung cancer and is linked to exposure to tobacco smoke.

Aged↗

PubMed2004

Asp85tyr polymorphism in the udp-glucuronosyltransferase (UGT) 2B15 gene and the risk of prostate cancer.

PURPOSE: An amino acid changing polymorphism in the UDP-glucuronosyltransferase (UGT) 2B15 gene has been described at codon 85 (aspartate>tyrosine). The UGT2B15 allele exhibits 2-fold decreased activity for dihydrotestosterone, which was suggested to be associated with the risk of prostate cancer based on in vitro functional analysis. We determined whether this polymorphism can be used to predict individual susceptibility to prostate cancer. MATERIALS AND METHODS: UGT2B15 expression was determined by reverse transcription-polymerase chain reaction of normal prostate tissues. Prevalence of the UGT2B15 Asp85Tyr polymorphism was compared between cases and controls by allele specific polymerase chain reaction analysis using genomic DNA isolated from 155 incident white patients with primary prostate cancer and 155 individually age matched (+/-5 years) white controls. RESULTS: UGT2B15 mRNA was detected in all prostate tissues tested. A significant association was found between UGT2B15 genotypes and prostate cancer risk. A significantly increased risk of prostate cancer was observed in subjects with the homozygous UGT2B15 genotype (OR 2.7, 95% CI 1.1 to 6.6). CONCLUSIONS: These results suggest that the UGT2B15 enzyme may have a role in the metabolism of dihydrotestosterone in prostate tissue and UGT2B15 Asp85Tyr polymorphism is associated with prostate cancer risk.

Aged↗

PubMed2003

Visualisation and graph-theoretic analysis of a large-scale protein structural interactome.

BACKGROUND: Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network. RESULTS: We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network. CONCLUSIONS: Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level.

Archaeal Proteins↗

PubMed2003

Association between polymorphism of human oxoguanine glycosylase 1 and risk of prostate cancer.

PURPOSE: The human oxoguanine glycosylase 1 (hOGG1) gene encodes a DNA glycosylase that is involved in excision repair of 8-OH-dG (8-hydroxy-2-deoxyguanine) from oxidatively damaged DNA. To determine whether hOGG1 has a role in the risk of prostate cancer we screened normal prostate tissue specimens for hOGG1 expression and assessed the role of hOGG1 Ser326Cys polymorphism in the risk of prostate cancer. MATERIALS AND METHODS: In 5 normal prostate tissues hOGG1 expression was determined by reverse transcriptase-polymerase chain reaction. The prevalence of hOGG1 Ser326Cys polymorphism was compared between white patients cases and controls using polymerase chain reaction restriction fragment length polymorphism analysis of genomic DNA isolated from 84 incident patients with primary prostate cancer and 252 individually matched controls (1:3 ratio) by age (+/- 5 years at diagnosis) in white men. RESULTS: In all prostate tissues tested hOGG1 mRNA was detected. A significant association was found between hOGG1 genotypes and prostate cancer with a dose effect relationship (trend test p <0.003). A significantly increased risk of prostate cancer was observed for subjects with hOGG1(326Cys) allele (ORadj 2.1, 95% CI 1.2-3.8). CONCLUSIONS: These results suggest that hOGG1 may have a role in the repair of 8-OH-dG adducts in prostate tissue and hOGG1 Ser326Cys polymorphism is associated with prostate cancer risk.

Adenocarcinoma↗

PubMed2002

Sequence similarity between stereocilin and otoancorin points to a unified mechanism for mechanotransduction in the mammalian inner ear.

BACKGROUND: Interaction between hair cells and acellular gels of the mammalian inner ear, the tectorial and otoconial membranes, is crucial for mechanoreception. Recently, otoancorin was suggested to be a mediator of gel attachment to nonsensory cells, but the molecular components of the interface between gels and sensory cells remain to be identified. HYPOTHESIS: We report that the inner ear protein stereocilin is related in sequence to otoancorin and, based on its localisation and predicted GPI-anchoring, may mediate attachment of the tectorial and otoconial membranes to sensory hair bundles. TESTING: It is expected that antibodies directed against stereocilin would specifically label sites of contact between sensory hair cells and tectorial/otoconial membranes of the inner ear. IMPLICATIONS: Our findings support a unified molecular mechanism for mechanotransduction, with stereocilin and otoancorin defining a new protein family responsible for the attachment of acellular gels to both sensory and nonsensory cells of the inner ear.

Amino Acid Sequence↗

PubMed2002

The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk.

The human OGG1 (hOGG1) gene encodes a DNA glycosylase that is involved in the excision repair of 8-hydroxy-2'-deoxyguanine (8-OH-dG) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in risk for orolaryngeal cancer, we screened normal orolaryngeal tissue specimens for hOGG1 expression and assessed the role of the hOGG1 Ser326Cys polymorphism in risk for orolaryngeal cancer. hOGG1 expression was determined by reverse transcription-polymerase chain reaction of total RNA from aerodigestive tract tissues, and hOGG1 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis of buccal cell DNA isolated from 169 Caucasian orolaryngeal cancer cases and 338 race-, sex- and age-matched controls. hOGG1 mRNA was detected in all aerodigestive tract tissues tested including tonsil, tongue, floor of mouth, larynx and esophagus. Significantly increased risk for orolaryngeal cancer was observed for both the hOGG1 326(Ser)/326(Cys) (odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.04-2.6) and hOGG1 326(Cys)/326(Cys) (OR = 4.1, 95% CI = 1.3-13) genotypes. Although no significant difference in risk for orolaryngeal cancer was observed for hOGG1 genotypes in never-smokers, increased risk for orolaryngeal cancer was observed for subjects with the homozygous polymorphic hOGG1 326(Cys)/326(Cys) genotype in smokers (>100 cigarettes lifetime; OR = 4.8, 95% CI = 1.3-18). Similarly, although no association was observed in never drinkers of alcohol, significantly increased risk was observed for the hOGG1 326(Cys)/326(Cys) genotype in alcohol drinkers (>1 shot/week; OR = 6.9, 95% CI = 1.6-29). These results suggest that hOGG1 may play an important role in the repair of 8-OH-dG adducts in the aerodigestive tract and that the hOGG1 Ser326Cys polymorphism plays an important role in risk for smoking- and alcohol-related orolaryngeal cancer.

Adult↗

PubMed2002

Large scale statistical prediction of protein-protein interaction by potentially interacting domain (PID) pair.

Protein-protein interaction plays a critical role in biological processes. The identification of interacting proteins by computational methods can provide new leads in functional studies of uncharacterized proteins without performing extensive experiments. We developed a database for the potentially interacting domain pairs (PID) extracted from a dataset of experimentally identified interacting protein pairs (DIP: database of interacting proteins) with InterPro, an integrated database of protein families, domains and functional sites. In developing protein interaction databases and predictive methods, sensitive statistical scoring systems is critical to provide a reliability index for accurate functional analysis of interaction networks. We present a statistical scoring system, named "PID matrix score" as a measure of the interaction probability (interactability) between domains. This system provided a valuable tool for functional prediction of unknown proteins. For the evaluation of PID matrix, cross validation was performed with subsets of DIP data. The prediction system gives about 50% sensitivity and more than 98% specificity, which implies that the information for interacting proteins pairs could be enriched about 30 fold with the PID matrix. It is demonstrated that mapping of the genome-wide interaction network can be achieved by using the PID matrix.

Algorithms↗