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Articles by D Choi
Total Records ( 6 ) for D Choi
  D Choi , A Radziszewska , S. A Schroer , N Liadis , Y Liu , Y Zhang , P. P. L Lam , L Sheu , Z Hao , H. Y Gaisano and M. Woo

Fas/Fas ligand belongs to the tumor necrosis factor superfamily of receptors/ligands and is best known for its role in apoptosis. However, recent evidence supports its role in other cellular responses, including proliferation and survival. Although Fas has been implicated as an essential mediator of β-cell death in the pathogenesis of type 1 diabetes, the essential role of Fas specifically in pancreatic β-cells has been found to be controversial. Moreover, the role of Fas on β-cell homeostasis and function is not clear. The objective of this study is to determine the role of Fas specifically in β-cells under both physiological and diabetes models. Mice with Fas deletion specifically in the β-cells were generated using the Cre-loxP system. Cre-mediated Fas deletion was under the control of the rat insulin promoter. Absence of Fas in β-cells leads to complete protection against FasL-induced cell death. However, Fas is not essential in determining β-cell mass or susceptibility to streptozotocin- or HFD-induced diabetes. Importantly, Fas deletion in β-cells leads to increased p65 expression, enhanced glucose tolerance, and glucose-stimulated insulin secretion, with increased exocytosis as manifested by increased changes in membrane capacitance and increased expression of Syntaxin1A, VAMP2, and munc18a. Together, our study shows that Fas in the β-cells indeed plays an essential role in the canonical death receptor-mediated apoptosis but is not essential in regulating β-cell mass or diabetes development. However, β-cell Fas is critical in the regulation of glucose homeostasis through regulation of the exocytosis machinery.

  D Choi and M. Woo

Pancreatic β-cell mass is dynamic and is regulated by β-cell proliferation, neogenesis, and apoptosis. Under physiological conditions, apoptosis is tightly regulated with a slow, net rise in β-cell mass over time. Excessive β-cell apoptosis is an important contributor to both type 1 and type 2 diabetes development. Therefore, much effort has been given recently to better understand the mechanisms of apoptosis that occur both during physiological homeostasis and during the course of both types of diabetes. Caspases are the executioners of apoptosis that ultimately result in cell suicide. In mammals, there are 14 caspases, of which many participate in the apoptotic pathways. Genetic mouse models have been important tools for elucidation of the specific apoptotic pathways that play an essential role in β-cell apoptosis under physiological and pathological conditions. This review focuses on the diverse roles of each of the specific caspases and their regulators, unveiling both the classical apoptotic roles as well as emerging nonapoptotic roles.

  S. H Kim , J Lee , M. J Kim , Y. H Jeon , Y Park , D Choi , W. J Lee and H. K. Lim

OBJECTIVE. We compared the diagnostic performance of gadoxetic acid–enhanced MRI with that of triple-phase 16-, 40-, and 64-MDCT in the preoperative detection of hepatocellular carcinoma (HCC).

SUBJECTS AND METHODS. Sixty-two consecutively registered patients (54 men, eight women; age range, 31–67 years) with 83 HCCs underwent triple-phase (arterial, portal venous, equilibrium) CT at 16-, 40-, or 64-MDCT and gadoxetic acid–enhanced 3-T MRI. The diagnosis of HCC was established after surgical resection. Three observers independently and randomly reviewed the MR and CT images on a tumor-by-tumor basis. The diagnostic accuracy of these techniques in the detection of HCC was assessed with alternative free response receiver operating characteristic (ROC) analysis. Sensitivity, positive and negative predictive values, and sensitivity according to tumor size were evaluated.

RESULTS. For each observer, the areas under the ROC curve were 0.971, 0.959, and 0.967 for MRI and 0.947, 0.950, and 0.943 for CT. The differences were not statistically significant between the two techniques for each observer (p > 0.05). The differences in sensitivity and positive and negative predictive values between the two techniques for each observer were not statistically significant (p > 0.05). Among 10 HCCs 1 cm in diameter or smaller, each of the observers detected seven tumors with MRI. With CT, one observer detected five, one observer detected four, and one observer detected three HCCs with no statistically significant difference (p > 0.05).

CONCLUSION. Gadoxetic acid–enhanced MRI and triple-phase MDCT have similar diagnostic performance in the preoperative detection of HCC, but MRI may be better than MDCT in the detection of HCC 1 cm in diameter or smaller.

  B. K Koo , K Waseda , H. J Kang , H. S Kim , C. W Nam , S. H Hur , J. S Kim , D Choi , Y Jang , J. Y Hahn , H. C Gwon , M. H Yoon , S. J Tahk , W. Y Chung , Y. S Cho , D. J Choi , T Hasegawa , T Kataoka , S. J Oh , Y Honda , P. J Fitzgerald and W. F. Fearon

Background— We sought to investigate the mechanism of geometric changes after main branch (MB) stent implantation and to identify the predictors of functionally significant "jailed" side branch (SB) lesions.

Methods and Results— Seventy-seven patients with bifurcation lesions were prospectively enrolled from 8 centers. MB intravascular ultrasound was performed before and after MB stent implantation, and fractional flow reserve was measured in the jailed SB. The vessel volume index of both the proximal and distal MB was increased after stent implantation. The plaque volume index decreased in the proximal MB (9.1±3.0 to 8.4±2.4 mm3/mm, P=0.001), implicating plaque shift, but not in the distal MB (5.4±1.8 to 5.3±1.7 mm3/mm, P=0.227), implicating carina shifting to account for the change in vessel size (N=56). The mean SB fractional flow reserve was 0.71±0.20 (N=68) and 43% of the lesions were functionally significant. Binary logistic-regression analysis revealed that preintervention % diameter stenosis of the SB (odds ratio=1.05; 95% CI, 1.01 to 1.09) and the MB minimum lumen diameter located distal to the SB ostium (odds ratio=3.86; 95% CI, 1.03 to 14.43) were independent predictors of functionally significant SB jailing. In patients with ≥75% stenosis and Thrombolysis In Myocardial Infarction grade 3 flow in the SB, no difference in poststent angiographic and intravascular ultrasound parameters was found between SB lesions with and without functional significance.

Conclusions— Both plaque shift from the MB and carina shift contribute to the creation/aggravation of an SB ostial lesion after MB stent implantation. Anatomic evaluation does not reliably predict the functional significance of a jailed SB stenosis.

Clinical Trial Registration: Unique Identifier: NCT00553670.

  D Choi , M Getmansky , B Henderson and H. Tookes

This article examines the potential impact of capital supply on security issuance. We focus on the role of convertible bond arbitrageurs as suppliers of capital to convertible bond issuers. We estimate a simultaneous equations model of demand and supply of convertible bond capital, linking the time series of aggregate convertible bond issuance to measures of capital supply: convertible bond arbitrage hedge fund flows, returns, and a proxy for arbitrageurs’ use of leverage. We find that issuance is positively and significantly related to increases in all three supply measures. To provide further interpretation, we use the September/October 2008 short-selling ban as a natural experiment to examine the impact of an exogenous shock to the supply of capital from arbitrageurs. Results from both empirical approaches provide evidence that the supply of capital from convertible bond arbitrageurs impacts issuance.

  V Musahl , M Citak , P. F O'Loughlin , D Choi , A Bedi and A. D. Pearle

Background: The pivot shift is a dynamic test of knee stability that involves a pathologic, multiplanar motion path elicited by a combination of axial load and valgus force during a knee flexion from an extended position.

Purpose: To assess the stabilizing effect of the medial and lateral meniscus on anterior cruciate ligament-deficient (ACL-D) knees during the pivot shift examination.

Study Design: Controlled laboratory study.

Methods: A Lachman and a mechanized pivot shift test were performed on 16 fresh-frozen cadaveric hip-to-toe lower extremity specimens. The knee was tested intact, ACL-D, and after sectioning the medial meniscus (ACL/MM-D; n = 8), lateral meniscus (ACL/LM-D; n = 8), and both (ACL/LM/MM-D; n = 16). A navigation system recorded the resultant anterior tibial translations (ATTs). For statistical analysis an analysis of variance was used; significance was set at P < .05.

Results: The ATT significantly increased in the ACL-D knee after lateral meniscectomy (ACL/LM-D; P < .05) during the pivot shift maneuver. In the lateral compartment of the knee, ATT in the ACL-D knee increased by 6 mm after lateral meniscectomy during the pivot shift (16.6 ± 6.0 vs 10.5 ± 3.5 mm, P < .01 for ACL/LM out vs ACL out). Medial meniscectomy, conversely, had no significant effect on ATT in the ACL-D knee during pivot shift examination (P > .05). With standardized Lachman examination, however, ATT significantly increased after medial but not lateral meniscectomy compared with the ACL-D knee (P < .001).

Conclusion: Although the medial meniscus functions as a critical secondary stabilizer to anteriorly directed forces on the tibia during a Lachman examination, the lateral meniscus appears to be a more important restraint to anterior tibial translation during combined valgus and rotatory loads applied during a pivoting maneuver.

Clinical Relevance: This model may have implications in the evaluation of surgical reconstruction procedures in complex knee injuries.

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