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Articles by N. H Kim
Total Records ( 5 ) for N. H Kim
  K. W Jensen , K. M Kerr , P. F Fedullo , N. H Kim , V. J Test , O Ben Yehuda and W. R. Auger

Background— The currently recommended treatment for chronic thromboembolic pulmonary hypertension is pulmonary thromboendarterectomy (PTE). No convincing evidence for the use of pulmonary hypertensive medical therapy (PHT) exists in operable candidates. We sought to determine the prevalence of the use of PHT on referral for PTE and the effects on pre-PTE hemodynamics and post-PTE outcomes/hemodynamics.

Methods and Results— We performed a retrospective analysis of chronic thromboembolic pulmonary hypertension patients referred for PTE during 2005–2007. The prevalence of PHT was determined for all patients referred to our institution. Hemodynamic and outcomes analysis involved only those undergoing PTE. Data included baseline demographics, PHT medication(s), dosage, duration of therapy, and time to referral. Hemodynamic data were acquired from the time of diagnosis, the time of referral visit, and after PTE. Outcomes included intensive care unit, hospital, and ventilator days; bleeding and infection rates; incidence of reperfusion lung injury; and in-hospital mortality. The control group (n=244) was compared with the PHT group (n=111); subgroups included monotherapy with bosentan, sildenafil, or epoprostenol and combination therapy. The prevalence of PHT significantly increased from 19.9% in 2005 to 37% in 2007. There was minimal benefit of treatment with PHT on pre-PTE mean pulmonary artery pressure, but its use was associated with a significant delay in time to referral for PTE. Both groups experienced significant improvements in hemodynamic parameters after PTE. The 2 groups did not differ significantly in any post-PTE outcome. Similar results were obtained for each subgroup.

Conclusions— Our results suggest that PHT use has minimal effect on pre-PTE hemodynamics and no effect on post-PTE outcomes/hemodynamics.

  T. N Kim , S Kim , S. J Yang , H. J Yoo , J. A Seo , N. H Kim , S. H Baik , D. S Choi and K. M. Choi

Background— Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular disease. Vascular inflammation is a key factor in both the pathogenesis and outcome of atherosclerosis. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a promising tool for indentifying and quantifying vascular inflammation within atherosclerotic plaques. This study was designed to examine the vascular inflammation measured using FDG-PET in patients with impaired glucose tolerance and T2DM, in comparison with age- and sex-matched control subjects with normal glucose tolerance.

Methods and Results— We investigated vascular inflammation using FDG-PET in 90 age- and sex-matched subjects with different glucose tolerance (30 normal glucose tolerance subjects, 30 impaired glucose tolerance subjects, and 30 T2DM subjects). Vascular 18F-FDG uptake was measured as both the mean and maximum blood-normalized standardized uptake value, known as the target-to-background ratio (TBR). Both mean and maximum TBR measurements were significantly different, based on glucose tolerance, although the carotid intima-media thickness measurements were not significantly different. The maximum TBR values in patients with impaired glucose tolerance and T2DM were significantly increased compared with the normal subjects. In addition, subjects with metabolic syndrome had increased maximum TBR values compared with those without metabolic syndrome. Age-, sex-, and body mass index–adjusted maximum TBR levels were positively correlated with triglyceride, hemoglobin A1c, insulin resistance, high-sensitivity C-reactive protein, and Framingham risk score and were negatively correlated with high-density lipoprotein cholesterol and adiponectin levels.

Conclusions— The results of the present study suggest that impaired glucose tolerance and T2DM are associated with vascular inflammation in carotid atherosclerosis detected by FDG-PET.

  J. Y Um , C. H Jang , K. Y Kim , S. J Kim , N. H Kim , P. D Moon , I. Y Choi , N. Y Myung , H. J Jeong , S. H Hong and H. M. Kim

Auditory dysfunction is related to large/small vessel occlusions and hemorrhage. Sudden sensorineural hearing loss (SSNHL) frequently occurs with anterior inferior cerebellar artery occlusion proximal to the internal auditory artery. Moreover, SSNHL has various pathogenetic mechanisms, the main proposed mechanisms being vascular disease, membrane ruptures, infection, and autoimmunity. Tumor necrosis factor (TNF) is an important cytokine in the inflammation process of cerebrovascular diseases. In the current study, the possible effects of polymorphisms in TNF- and TNF-β genes on SSNHL are evaluated. Two genetic polymorphisms in the TNF locus (TNF- —308 G - ->A and TNF-β +252 A - ->G) were investigated as risk factors for SSNHL by determining their prevalence in 97 SSNHL patients and in 587 controls. A significant increase was found for the TNF-β allele 1 in SSNHL patients compared with the controls ( 2 = 7.251, P = .007, odds ratio [OR] = 1.534, confidence interval [CI] = 1.12-2.10). These findings suggest that the TNF-β +252 locus plays an important role in the etiopathogenesis of SSNHL.

  I Lee , S. S Ajay , J. I Yook , H. S Kim , S. H Hong , N. H Kim , S. M Dhanasekaran , A. M Chinnaiyan and B. D. Athey

MicroRNAs (miRNAs) are known to post-transcriptionally regulate target mRNAs through the 3'-UTR, which interacts mainly with the 5'-end of miRNA in animals. Here we identify many endogenous motifs within human 5'-UTRs specific to the 3'-ends of miRNAs. The 3'-end of conserved miRNAs in particular has significant interaction sites in the human-enriched, less conserved 5'-UTR miRNA motifs, while human-specific miRNAs have significant interaction sites only in the conserved 5'-UTR motifs, implying both miRNA and 5'-UTR are actively evolving in response to each other. Additionally, many miRNAs with their 3'-end interaction sites in the 5'-UTRs turn out to simultaneously contain 5'-end interaction sites in the 3'-UTRs. Based on these findings we demonstrate combinatory interactions between a single miRNA and both end regions of an mRNA using model systems. We further show that genes exhibiting large-scale protein changes due to miRNA overexpression or deletion contain both UTR interaction sites predicted. We provide the predicted targets of this new miRNA target class, miBridge, as an efficient way to screen potential targets, especially for nonconserved miRNAs, since the target search space is reduced by an order of magnitude compared with the 3'-UTR alone. Efficacy is confirmed by showing SEC24D regulation with hsa-miR-605, a miRNA identified only in primate, opening the door to the study of nonconserved miRNAs. Finally, miRNAs (and associated proteins) involved in this new targeting class may prevent 40S ribosome scanning through the 5'-UTR and keep it from reaching the start-codon, preventing 60S association.

  Y. S Kim , N. H Kim , S. J Yeom , S. W Kim and D. K. Oh

Codon optimization was used to synthesize the blh gene from the uncultured marine bacterium 66A03 for expression in Escherichia coli. The expressed enzyme cleaved β-carotene at its central double bond (15,15') to yield two molecules of all-trans-retinal. The molecular mass of the native purified enzyme was ~64 kDa as a dimer of 32-kDa subunits. The Km, kcat, and kcat/Km values for β-carotene as substrate were 37 µm, 3.6 min–1, and 97 mm–1 min–1, respectively. The enzyme exhibited the highest activity for β-carotene, followed by β-cryptoxanthin, β-apo-4'-carotenal, -carotene, and -carotene in decreasing order, but not for β-apo-8'-carotenal, β-apo-12'-carotenal, lutein, zeaxanthin, or lycopene, suggesting that the presence of one unsubstituted β-ionone ring in a substrate with a molecular weight greater than C35 seems to be essential for enzyme activity. The oxygen atom of retinal originated not from water but from molecular oxygen, suggesting that the enzyme was a β-carotene 15,15'-dioxygenase. Although the Blh protein and β-carotene 15,15'-monooxygenases catalyzed the same biochemical reaction, the Blh protein was unrelated to the mammalian β-carotene 15,15'-monooxygenases as assessed by their different properties, including DNA and amino acid sequences, molecular weight, form of association, reaction mechanism, kinetic properties, and substrate specificity. This is the first report of in vitro characterization of a bacterial β-carotene-cleaving enzyme.

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