Biomedical subjects

Hye-Won Shin

Publications and source records attributed to Hye-Won Shin.

24 records · Page 2Linked to original sources

PubMed2003

Airway diffusing capacity of nitric oxide and steroid therapy in asthma.

Exhaled nitric oxide (NO) concentration is a noninvasive index for monitoring lung inflammation in diseases such as asthma. The plateau concentration at constant flow is highly dependent on the exhalation flow rate and the use of corticosteroids and cannot distinguish airway and alveolar sources. In subjects with steroid-naive asthma (n = 8) or steroid-treated asthma (n = 12) and in healthy controls (n = 24), we measured flow-independent NO exchange parameters that partition exhaled NO into airway and alveolar regions and correlated these with symptoms and lung function. The mean (+/-SD) maximum airway flux (pl/s) and airway tissue concentration [parts/billion (ppb)] of NO were lower in steroid-treated asthmatic subjects compared with steroid-naive asthmatic subjects (1,195 +/- 836 pl/s and 143 +/- 66 ppb compared with 2,693 +/- 1,687 pl/s and 438 +/- 312 ppb, respectively). In contrast, the airway diffusing capacity for NO (pl.s-1.ppb-1) was elevated in both asthmatic groups compared with healthy controls, independent of steroid therapy (11.8 +/- 11.7, 8.71 +/- 5.74, and 3.13 +/- 1.57 pl.s-1.ppb-1 for steroid treated, steroid naive, and healthy controls, respectively). In addition, the airway diffusing capacity was inversely correlated with both forced expired volume in 1 s and forced vital capacity (%predicted), whereas the airway tissue concentration was positively correlated with forced vital capacity. Consistent with previously reported results from Silkoff et al. (Silkoff PE, Sylvester JT, Zamel N, and Permutt S, Am J Respir Crit Med 161: 1218-1228, 2000) that used an alternate technique, we conclude that the airway diffusing capacity for NO is elevated in asthma independent of steroid therapy and may reflect clinically relevant changes in airways.

Adolescent↗

PubMed2003

Impact of high-intensity exercise on nitric oxide exchange in healthy adults.

PURPOSE: After exercise, exhaled NO concentration has been reported to decrease, remain unchanged, or increase. A more mechanistic understanding of NO exchange dynamics after exercise is needed to understand the relationship between exercise and NO exchange. METHODS: We measured several flow-independent NO exchange parameters characteristic of airway and alveolar regions using a single breath maneuver and a two-compartment model (maximum flux of NO from the airways, J'(awNO), pL x s-1; diffusing capacity of NO in the airways, D(awNO), pL x s-1 x ppb-1; steady state alveolar concentration, C(alv,ss), ppb; mean airway tissue NO concentration, C(awNO), ppb), as well as serum IL-6 at baseline, 3, 30, and 120 min after a high-intensity exercise challenge in 10 healthy adults (21-37 yr old). RESULTS: D(awNO) (mean +/- SD) increased (37.1 +/- 44.4%), whereas J'(awNO) and C(awNO) decreased (-7.27 +/- 11.1%, -26.1 +/- 24.6%, respectively) 3 min postexercise. IL-6 increased steadily after exercise to 481% +/- 562% above baseline 120 min postexercise. CONCLUSION: High-intensity exercise acutely enhances the ability of NO to diffuse between the airway tissue and the gas phase, and exhaled NO might be used to probe both the metabolic and physical properties of the airways.

Adult↗

PubMed2002

Impact of axial diffusion on nitric oxide exchange in the lungs.

Nitric oxide (NO) appears in the exhaled breath and is a potentially important clinical marker. The accepted model of NO gas exchange includes two compartments, representing the airway and alveolar region of the lungs, but neglects axial diffusion. We incorporated axial diffusion into a one-dimensional trumpet model of the lungs to assess the impact on NO exchange dynamics, particularly the impact on the estimation of flow-independent NO exchange parameters such as the airway diffusing capacity and the maximum flux of NO in the airways. Axial diffusion reduces exhaled NO concentrations because of diffusion of NO from the airways to the alveolar region of the lungs. The magnitude is inversely related to exhalation flow rate. To simulate experimental data from two different breathing maneuvers, NO airway diffusing capacity and maximum flux of NO in the airways needed to be increased approximately fourfold. These results depend strongly on the assumption of a significant production of NO in the small airways. We conclude that axial diffusion may decrease exhaled NO levels; however, more advanced knowledge of the longitudinal distribution of NO production and diffusion is needed to develop a complete understanding of the impact of axial diffusion.

Diffusion↗

PubMed2002

Flow-independent nitric oxide exchange parameters in cystic fibrosis.

Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C(NO,plat)) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n = 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J(NO,max'), pl s(-1)), diffusing capacity of NO in the airways (D(NO,air'), pl s(-1) ppb(-1)), steady-state alveolar concentration (C(alv,ss'), ppb), and mean tissue concentration of NO in the airways (C(tiss,air'), ppb). We determined the following mean (+/- SD) values in the healthy children and patients with CF for J(NO,max'), D(NO,air'), C(alv,ss'), and C(tiss,air'), respectively: 784 +/- 465 and 607 +/- 648 pl s(-1); 4.82 +/- 3.07 and 17.6 +/- 12.1 pl s(-1) ppb(-1); 4.63 +/- 3.59 and 1.96 +/- 1.18 ppb; and 198 +/- 131 and 38 +/- 25 ppb. D(NO,air) is elevated (p = 0.007), and both C(alv,ss) and C(tiss,air) are reduced (p = 0.05 and 0.002, respectively) in CF. In contrast, C(NO,plat) for healthy control subjects and patients with CF are not statistically different at both exhalation flow rates of 50 ml/s (17.5 +/- 11.5 and 11.5 +/- 8.97) and at 250 ml/s (7.11 +/- 5.36 and 4.28 +/- 3.43). We conclude that D(NO,air'), C(tiss,air'), and C(alv,ss) may be useful noninvasive markers of CF.

Adolescent↗

PubMed2002

Phosphoinositides regulate membrane-dependent actin assembly by latex bead phagosomes.

Actin assembly on membrane surfaces is an elusive process in which several phosphoinositides (PIPs) have been implicated. We have reconstituted actin assembly using a defined membrane surface, the latex bead phagosome (LBP), and shown that the PI(4,5)P(2)-binding proteins ezrin and/or moesin were essential for this process (). Here, we provide several lines of evidence that both preexisting and newly synthesized PI(4,5)P(2), and probably PI(4)P, are essential for phagosomal actin assembly; only these PIPs were routinely synthesized from ATP during in vitro actin assembly. Treatment of LBP with phospholipase C or with adenosine, an inhibitor of type II PI 4-kinase, as well as preincubation with anti-PI(4)P or anti-PI(4,5)P(2) antibodies all inhibited this process. Incorporation of extra PI(4)P or PI(4,5)P(2) into the LBP membrane led to a fivefold increase in the number of phagosomes that assemble actin. An ezrin mutant mutated in the PI(4,5)P(2)-binding sites was less efficient in binding to LBPs and in reconstituting actin assembly than wild-type ezrin. Our data show that PI 4- and PI 5-kinase, and under some conditions also PI 3-kinase, activities are present on LBPs and can be activated by ATP, even in the absence of GTP or cytosolic components. However, PI 3-kinase activity is not required for actin assembly, because the process was not affected by PI 3-kinase inhibitors. We suggest that the ezrin-dependent actin assembly on the LBP membrane may require active turnover of D4 and D5 PIPs on the organelle membrane.

Binding Sites↗

PubMed2002

Gamma-adaptin interacts directly with Rabaptin-5 through its ear domain.

In yeast two-hybrid screening using gamma1-adaptin, a subunit of the AP-1 adaptor complex of clathrin-coated vesicles derived from the trans-Golgi network (TGN), as bait, we found that it could interact with Rabaptin-5, an effector of Rab5 and Rab4 that regulates membrane docking with endosomes. Further two-hybrid analysis revealed that the interaction occurs between the ear domain of gamma1-adaptin and the COOH-terminal coiled-coil region of Rabaptin-5. Pull down assay with a fusion protein between glutathione S-transferase and the ear domain of gamma1-adaptin and coimmunoprecipitation analysis revealed that the interaction occurs in vitro and in vivo. Immunocytochemical analysis showed that gamma1-adaptin and Rabaptin-5 colocalize to a significant extent on perinuclear structures, probably on recycling endosomes, and are redistributed into the cytoplasm upon treatment with brefeldin A. These results suggest that the gamma1-adaptin-Rabaptin-5 interaction may play a role in membrane trafficking between the TGN and endosomes.

Adaptor Protein Complex gamma Subunits↗