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Articles by S. J Park
Total Records ( 9 ) for S. J Park
  S. J Park , H. Y Yoo , Y. E Earm , S. J Kim , J. K Kim and S. D. Kim
  Background

The roles of arachidonic acid (AA) metabolites in hypoxia-induced pulmonary vasoconstriction (HPV), a critical physiological mechanism that prevents ventilation/perfusion mismatch, are still incompletely understood.

Methods

Pulmonary arterial pressure was measured in ventilated/perfused rat lungs. Isometric tones of rat intralobar pulmonary arteries were also measured, using a myograph.

Results

Hypoxia (Po2, 3%)-induced pulmonary arterial pressure increases (PAPhypox) were stable with blood-mixed perfusate, but decayed spontaneously. PAPhypox was inhibited by 29%, 16%, and 28% by the thromboxane A2 (TXA2) antagonist SQ-29548, the 5-lipoxygenase inhibitor, MK886, and the leukotriene D4 antagonist, LY-171883, respectively. The prostacyclin synthase inhibitor tranylcypromine augmented PAPhypox by 5%, whereas inhibition of cytochrome P450 did not affect PAPhypox. Consistently, the TXA2 analogue U46619 increased PAPhypox whereas prostacyclin abolished PAPhypox. However, leukotriene D4 had no direct effect on PAPhypox. In the isolated pulmonary arteries, pretreatment with U46619 was essential to demonstrate hypoxia-induced contraction.

Conclusions

The above results suggest that TXA2 and cysteinyl leukotrienes, other than leukotriene D4, are endogenous factors that facilitate HPV in rats. The indispensable role of TXA2-induced pretone in the HPV of isolated pulmonary arteries indicates that the signal from thromboxane receptors might be a critical component of oxygen sensation mechanisms.

  S. J Park , Y. H Kim , D. W Park , S. W Lee , W. J Kim , J Suh , S. C Yun , C. W Lee , M. K Hong , J. H Lee , S. W Park and for the MAIN COMPARE Investigators
 

Background— Although intravascular ultrasound (IVUS) guidance has been useful in stenting for unprotected left main coronary artery stenosis, its impact on long-term mortality is still unclear.

Methods and Results— In the MAIN-COMPARE registry, patients with unprotected left main coronary artery stenosis in a hemodynamically stable condition underwent elective stenting under the guidance of IVUS (756 patients) or conventional angiography (219 patients). Patients with acute myocardial infarction were excluded. The 3-year outcomes between the 2 groups were primarily compared using propensity-score matching in the entire and separate populations according to stent type. In 201 matched pairs of the overall population, there was a tendency of lower risk of 3-year morality with IVUS guidance compared with angiography guidance (6.0% versus 13.6%, log-rank P=0.063; hazard ratio, 0.54; 95% CI, 0.28 to 1.03; Cox-model P=0.061). In particular, in 145 matched pairs of patients receiving drug-eluting stent, the 3-year incidence of mortality was lower with IVUS guidance as compared with angiography guidance (4.7% versus 16.0%, log-rank P=0.048; hazard ratio, 0.39; 95% CI, 0.15 to 1.02; Cox model P=0.055). In contrast, the use of IVUS guidance did not reduce the risk of mortality in 47 matched pairs of patients receiving bare-metal stent (8.6% versus 10.8%, log-rank P=0.35; hazard ratio, 0.59; 95% CI, 0.18 to 1.91; Cox model P=0.38). The risk of myocardial infarction or target vessel revascularization was not associated with the use of IVUS guidance.

Conclusions— Elective stenting with IVUS guidance, especially in the placement of drug-eluting stent, may reduce the long-term mortality rate for unprotected left main coronary artery stenosis when compared with conventional angiography guidance.

  B Chevalier , S Silber , S. J Park , E Garcia , G Schuler , H Suryapranata , J Koolen , K. E Hauptmann , W Wijns , M. C Morice , D Carrie , G. A van Es , H Nagai , D Detiege , D Paunovic , P. W Serruys and for the NOBORI 1 Clinical Investigators
 

Background— The newly developed Nobori coronary stent coated with a bioresorbable polymer, polylactic acid, and the antiproliferative agent Biolimus A9 has the potential to reduce restenosis by suppressing neointima formation.

Methods and Results— We conducted a randomized (2:1), controlled trial comparing the Biolimus A9-eluting stent Nobori and the paclitaxel-eluting stent Taxus Liberté, in 243 patients (153 Nobori and 90 Taxus) at 29 centers in Europe, Asia, and Australia. Patients with previously untreated lesions in up to 2 native coronary arteries were considered for enrollment. The primary end point was in-stent late loss at 9 months, whereas secondary end points included other quantitative coronary angiography parameters, such as in-segment late loss and the rate of restenosis as well as key intravascular ultrasound parameters. Clinical secondary end points were stent thrombosis and composite of major adverse cardiac events comprising death, myocardial infarction, and target vessel revascularization. At 9 months, the in-stent late loss was significantly lower in the Nobori group compared with the Taxus group (0.11±0.30 mm versus 0.32±0.50 mm) reaching both the primary hypothesis of noninferiority of Nobori stent versus Taxus Liberté stent (P<0.001) and the secondary hypothesis of superiority (P=0.001). This finding was confirmed by a significant reduction in binary restenosis from 6.2% in Taxus to 0.7% in Nobori (P=0.02) and neointimal volume obstruction, detected by intravascular ultrasound, from 5.5±7.2% in Taxus to 1.8±5.2% in Nobori (P=0.01). The major adverse cardiac events rate was 4.6% in the Nobori and 5.6% in the Taxus cohort of patients. The stent thrombosis rate was 0% in the Nobori arm and 4.4% in the Taxus arm.

Conclusions— The NOBORI 1 clinical trial confirmed its primary hypothesis—noninferiority of the Nobori Biolimus A9-eluting stent versus the Taxus Liberté stent in reducing neointimal proliferation. Both stents showed a low major adverse cardiac events rate in the studied population.

  S. J Lee , S. S Lee , H. J Jung , H. S Kim , S. J Park , C. W Yeo and J. G. Shin
 

Our objectives were to identify CYP2D6 genetic polymorphisms in a Korean population, to compare the allele frequencies with those of other ethnic groups, and to evaluate variant-induced functional variations in dextromethorphan (DM) metabolism in vitro and in vivo. Thirty-eight single nucleotide polymorphisms of CYP2D6 were identified by direct DNA sequencing in 51 Koreans. An extended set of 707 subjects were screened for the identified variants. A group of 202 healthy subjects was subjected to phenotypic analysis on DM metabolism. CYP2D6*10 was found to be the most frequent allele (45.6%), followed by CYP2D6*1 (32.3%), *2 (9.9%), *5 (5.6%), *41 (2.2%), *49 (1.4%), and some other rare alleles (<1%). The newly identified E418K and S183Stop were assigned as CYP2D6*52 and CYP2D6*60, respectively, by the Human P450 (CYP) Allele Nomenclature Committee. Individuals having the CYP2D6*10/*49 genotype (n = 5) exhibited a significant decrease in CYP2D6 metabolic activity compared with those with the CYP2D6*1/*1 genotype (n = 31) (P < 0.019). Variations in CYP2D6 protein levels in liver tissues (n = 49) were observed with CYP2D6 genotypes, and correlation between the CYP2D6 protein content and the activity was significant (r2 = 0.7). Given the importance of CYP2D6 in drug metabolism, subjects with the CYP2D6*10/*49 genotype may benefit from genotype analysis to achieve optimal drug therapy.

  S. J Lee , S. S Lee , H. J Jung , H. S Kim , S. J Park , C. W Yeo and J. G. Shin
 

Our objectives were to identify CYP2D6 genetic polymorphisms in a Korean population, to compare the allele frequencies with those of other ethnic groups, and to evaluate variant-induced functional variations in dextromethorphan (DM) metabolism in vitro and in vivo. Thirty-eight single nucleotide polymorphisms of CYP2D6 were identified by direct DNA sequencing in 51 Koreans. An extended set of 707 subjects were screened for the identified variants. A group of 202 healthy subjects was subjected to phenotypic analysis on DM metabolism. CYP2D6*10 was found to be the most frequent allele (45.6%), followed by CYP2D6*1 (32.3%), *2 (9.9%), *5 (5.6%), *41 (2.2%), *49 (1.4%), and some other rare alleles (<1%). The newly identified E418K and S183Stop were assigned as CYP2D6*52 and CYP2D6*60, respectively, by the Human P450 (CYP) Allele Nomenclature Committee. Individuals having the CYP2D6*10/*49 genotype (n = 5) exhibited a significant decrease in CYP2D6 metabolic activity compared with those with the CYP2D6*1/*1 genotype (n = 31) (P < 0.019). Variations in CYP2D6 protein levels in liver tissues (n = 49) were observed with CYP2D6 genotypes, and correlation between the CYP2D6 protein content and the activity was significant (r2 = 0.7). Given the importance of CYP2D6 in drug metabolism, subjects with the CYP2D6*10/*49 genotype may benefit from genotype analysis to achieve optimal drug therapy.

  S. J Park , Y. S Chun , K. S Park , S. J Kim , S. O Choi , H. L Kim and J. W. Park
 

Hypoxic inhibition of K+ current is a critical O2-sensing mechanism. Previously, it was demonstrated that the cooperative action of TASK-1 and NADPH oxidase-4 (NOX4) mediated the O2-sensitive K+ current response. Here we addressed the O2-sensing mechanism of NOX4 in terms of TASK-1 regulation. In TASK-1 and NOX4-coexpressing human embryonic kidney 293 cells, hypoxia (5% O2) decreased the amplitude of TASK-1 current (hypoxia-ITASK-1). To examine whether reactive oxygen species (ROS) mediate the hypoxia-ITASK-1, we treated the cells with carbon monoxide (CO) which is known to reduce ROS generation from the heme-containing NOX4. Unexpectedly, CO failed to mimic hypoxia in TASK-1 regulation, rather blocked the hypoxia-ITASK-1. Moreover, the hypoxia-ITASK-1 was neither recovered by H2O2 treatment nor prevented by antioxidant such as ascorbic acid. However, the hypoxia-ITASK-1 was noticeably attenuated by succinyl acetone, a heme synthase inhibitor. To further evaluate the role of heme, we constructed and expressed various NOX4 mutants, such as HBD(–) lacking the heme binding domain, NBD(–) lacking the NADPH binding domain, FBD(–) lacking the FAD binding domain, and HFBD(–) lacking both heme and FAD domains. The hypoxia-ITASK-1 was significantly reduced in HBD(–)-, FBD(–)-, or HFBD(–)-expressing cells, versus wild-type NOX4-expressing cells. However, NBD(–) did not affect the TASK-1 response to hypoxia. We also found that p22 is required for the NOX4-dependent TASK-1 regulation. These results suggest that O2 binding with NOX4 per se controls TASK-1 activity. In this process, the heme moiety and FBD seem to be responsible for the NOX4 regulation of TASK-1, and p22 might support the NOX4-TASK-1 interaction.

  J. K Seon , S. J Park , K. B Lee , H. R Gadikota , M Kozanek , L. S Oh , S Hariri and E. K. Song
  Background

Screw and suture fixations are the most commonly used methods of fixation in treatment of anterior cruciate ligament tibial avulsion fractures. Even though a few biomechanical studies have compared the stability of the 2 fixation techniques, a clinical comparison has not yet been reported.

Hypothesis

The authors hypothesized that both fixations would be identical in all studied clinical outcome measures at a minimum 2-year follow-up.

Study Design

Cohort study; Level of evidence, 3.

Materials and Methods

Thirty-three patients treated with either screw fixation (16 patients) or suture fixation (17 patients) within 1 month of the anterior cruciate ligament tibial avulsion fracture (type II or III) without associated ligamentous injury were included. All patients were evaluated at a minimum 2-year follow-up in terms of Lysholm knee scores and return to preinjury activities. Knee stability was compared based on the Lachman test and stress radiography.

Results

No significant differences were found between the 2 groups in terms of average Lysholm knee scores (91.7 in the screw group and 92.7 in the suture group, P = .413) at follow-up. All patients except 2 (1 in each group) returned to preinjury activity levels. However, flexion contractures (5° to 10°) were found in 3 patients in the screw group and 2 patients in the suture group without significant intergroup difference. Stabilities based on the Lachman test and instrumented stress radiography were also similar between the 2 groups at follow-up. However, 2 patients in the screw group and 1 in the suture group showed more than 5 mm laxity compared with the contralateral knee on stress radiographs.

Conclusion

Both the screw and suture fixation techniques for the anterior cruciate ligament tibial avulsion fracture produced relatively good results in terms of functional outcomes and stability without any significant differences. However, some patients in both groups showed residual laxity or flexion contractures.

  S. B Jang , A. R Kwon , W. S Son , S. J Park and B. J. Lee
 

The HP0062 gene encodes a small acidic protein of 86 amino acids with a theoretical pI of 4.6. The crystal structure of hypothetical protein HP0062 from Helicobacter pylori has been determined at 1.65 Å by molecular-replacement method. The crystallographic asymmetric unit contains dimer, in which HP0062 monomer folds into a helix–hairpin–helix structure. The two protomers are primarily held together by extensive hydrophobic interactions in an antiparallel arrangement, forming a four helix bundle. Aromatic residues located at a or g position in the heptad leucine zipper are not major contributor required for HP0062 dimerization but important for the thermostability of this protein.

  S. B Jang , C Ma , J. Y Lee , J. H Kim , S. J Park , A. R Kwon and B. J. Lee
 

The HP0827 protein is an 82-residue protein identified as a putative ss-DNA-binding protein 12RNP2 Precursor from Helicobacter pylori. Here, we have determined 3D structure of HP0827 using Nuclear Magnetic Resonance. It has a ferredoxin-like fold, β1–1–β2–β3–2–β4 (; -helix and β; β-sheet) and ribonucleoprotein (RNP) motifs which are thought to be important in RNA binding. By using structural homologues search and analyzing electrostatic potential of surface, we could compared HP0827 with other RNA-binding proteins (sex-lethal, T-cell restricted intracellular antigen-1, U1A) to predict RNA-binding sites of HP0827. We could predict that β sheets of HP0827, especially β1 and β3, are primary region for RNA binding. Consequently, similar to other RNA-binding proteins, RNP motifs (Y5, F45, F47), positively charged and hydrophobic regions (K32, R37, K40, K41, K43, R70, R73) are proposed as a putative RNA-binding sites. In addition, differences in amino acids composition of RNP motifs, N, C-terminal residues, loop-region fold and the orientation of 1-helix with other RNA recognition motif proteins could give specific biological functions to HP0827. Finally, the study on natural RNA target is also important to completely understand the biological function of HP0827.

 
 
 
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