Ki Young Kim

Remnant lipoprotein particles induce apoptosis in endothelial cells by NAD(P)H oxidase-mediated production of superoxide and cytokines via lectin-like oxidized low-density lipoprotein receptor-1 activation: prevention by cilostazol.

Background—Remnant lipoprotein particles (RLPs), products of lipolytic degradation of triglyceride-rich lipoprotein derived from VLDL, exert atherogenesis. In this study, we observed how RLPs induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and cilostazol prevented cell death. Methods and Results—RLPs were isolated from the plasma of hyperlipidemic patients by use of an immunoaffinity gel mixture of anti–apolipoprotein A-1 and anti–apolipoprotein B-100 monoclonal antibodies. RLPs (50 &mgr;g/mL) significantly increased superoxide formation in HUVECs associated with elevated gp91phox mRNA and protein expression and Rac1 translocation, accompanied by increased production of tumor necrosis factor (TNF)-&agr; and interleukin-1&bgr;, DNA fragmentation, and cell death. Cilostazol (1 to 100 &mgr;mol/L) significantly suppressed not only NAD(P)H oxidase–dependent superoxide production but also TNF-&agr; and interleukin-1&bgr; release and restored viability. RLPs activated a lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which was not inhibited by cilostazol. Treatment of HUVECs with monoclonal antibody for LOX-1 attenuated RLP-mediated production of superoxide, TNF-&agr;, and interleukin-1&bgr; and DNA fragmentation. Conclusions—RLPs stimulated NAD(P)H oxidase–dependent superoxide formation and induction of cytokines in HUVECs via activation of LOX-1, consequently leading to reduction in cell viability with DNA fragmentation, and cilostazol exerts a cell-protective effect by suppressing these variables.

A routing algorithm for a single straddle carrier to load export containers onto a containership

How to route a straddle carrier during loading operation of export containers in port container terminals is discussed. We try to minimize the total travel distance of the straddle carrier in the yard. We determine the number of containers which the straddle carrier picks up at each yard-bay as well as the sequence of yard-bays which the straddle carrier visits during the tour. The objective is to minimize the total travel time of the straddle carrier. This routing problem is formulated as an integer programming. An efficient optimizing algorithm is also developed for the carrier routing problem.

Routing straddle carriers for the loading operation of containers using a beam search algorithm

Abstract This paper discusses how to route straddle carriers during the loading operation of export containers in port container terminals. The objective of the routing is to minimize the total travel distance of straddle carriers in the yard. The routing problem is comprised of the container allocation problem and the carrier routing problem. In the container allocation problem, containers in the yard are divided into multiple classes, each of which will be loaded by a quay crane. The container allocation problem is formulated as a transportation problem. In the carrier routing problem, the sequence of yard-bays that a carrier visits is determined. A beam search algorithm is developed for the carrier routing problem. A numerical experimentation is carried out in order to evaluate the performance of the algorithm.

National Cancer Incidence for the Year 2002 in Korea

PURPOSEnSince the revised Cancer Act of October 2006, cancer registration was reactivated, based on the Statistics Law.nnnMATERIALS AND METHODSnThe incidence of cancer during 2002 was calculated on the basis of the information available from the National Cancer Incidence Database. Crude and age-standardized rates were calculated by gender for 18 age groups (0 approximately 4, 5 approximately 9, 10 approximately 14, every five years, 85 years and over).nnnRESULTSnThe overall crude incidence rates (CRs) were 269.2 and 212.8 per 100,000 for males and females, and the overall age-standardized incidence rates (ASRs) were 287.8 and 172.9 per 100,000, respectively. Among males, the five leading primary cancer sites were stomach (CR 62.4, ASR 65.7), lung (CR 45.4, ASR 51.0), liver (CR 43.2, ASR 43.7), colon and rectum (CR 30.7, ASR 32.7), and prostate (CR 8.0, ASR 9.6). Among females, the most common cancer sites were breast (CR 33.1, ASR 26.9), followed by stomach (CR 32.8, ASR 26.0), colon and rectum (CR 23.1, ASR 18.5), thyroid (CR 19.1, ASR 15.7), and uterine cervix (CR 18.2, ASR 14.7). In the 0~14 age group, leukemia was the most common cancer for both genders. For males, stomach cancer was the most common cancer in the 15 approximately 64 age-group, but lung cancer was more frequent in men 65 or older. For females, thyroid cancer among the 15 approximately 34 age-group, breast cancer among 35 approximately 64 age-group and stomach cancer in women 65 years or older were the most common forms of cancer for each age group. The quality indices for the percentage of deaths, by death certificate only, were 4.7% for males and 4.5% for females.nnnCONCLUSIONSnSince the National Cancer Incidence Database was started, the annual percent change of cancer cases increased by 4.8% (4.1% for males, 5.7% for females) during 1999 approximately 2002. This value reflects the increase in prostate cancer for males and breast and thyroid cancer in females during 2002. The timely reporting of improved quality of cancer registration is needed for evidence-based decisions regarding cancer control in Korea.

A routing algorithm for a single transfer crane to load export containers onto a containership

It is discussed how to route transfer crane during loading operation of export containers in port container terminal. We determine the number of containers which transfer crane picks up at each yard-bay as well as the sequence of yard-bays which transfer crane visits during the tour. The objective is to minimize the total container handling time of the transfer crane including the set-up time at each yard-bay and the travel time between consecutive yard-bays. This routing problem is formulated as an integer programming. An efficient optimizing algorithm is also developed for the crane routing problem.

Vascular NAD(P)H Oxidase Triggers Delayed Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats

Background and Purpose– To clarify the role of vascular NAD(P)H oxidase in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), both the activity and/or activation mechanisms of NAD(P)H oxidase in the cerebral vasculature and the effect of oxidase inhibition on SAH-induced cerebral vasospasm were assessed. Methods— The changes in the luminal perimeter of the middle cerebral artery were measured histologically after SAH was induced according to a 2-hemorrhage model in rats. The NAD(P)H oxidase activity in the cerebral vasculature was measured with a lucigenin assay at different time intervals from 12 hours to 14 days after injection of autologous blood into cisterna magna. The membrane translocation of p47phox and the protein expression of membrane subunits (gp91phox and p22phox) of NAD(P)H oxidase were analyzed using Western blot analysis. Results— The luminal perimeter of the middle cerebral artery started to decrease on day 1 and peaked on day 5 after a second injection of blood, and these changes were significantly ameliorated by treatment with an NAD(P)H oxidase inhibitor, diphenyleneiodonium. At 24 hours after the second injection of blood, both vascular production of superoxide anion and NAD(P)H oxidase activity were markedly increased with enhanced membrane translocation of p47phox, but by 48 hours the enzyme activity had regained normal values. However, no significant changes in the expression of gp91phox and p22phox were observed throughout the experiments. Conclusions— These findings suggest that the activation of NAD(P)H oxidase through enhanced assembly of the oxidase components in the early stages of SAH might contribute to the delayed cerebral vasospasm in SAH rats.

Neuroprotection by cilostazol, a phosphodiesterase type 3 inhibitor, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion.

In the present study, we elucidated effect of cilostazol to prevent the occurrence of vacuolation and rarefaction of the white matter in association with apoptosis induced by bilateral occlusion of common carotid arteries in the male Wistar rats. Rats orally received vehicle (DMSO) or 60 mg kg(-1) day(-1) (orally) cilostazol for 3, 7, 14 or 30 days. In the vehicle group, increased vacuolation and rarefactions in the white matter were accompanied by extensive activation of both microglial and astroglial cells with suppression of oligodendrocytes in association with increased TNF-alpha production, caspase-3 immunoreactivity and TUNEL-positive cells in the white matter including optic tract. Post-treatment with cilostazol (60 mg kg(-1) day(-1)) strongly suppressed not only elevated activation of astroglia and microglia but also diminished oligodendrocytes following chronic cerebral hypoperfusion. In conclusion, cilostazol (60 mg kg(-1) day(-1), orally) significantly reduced the apoptotic cell death in association with decreased TNF-alpha production and caspase-3-positive cells in the white matter of rat brains subjected to bilateral occlusion of common carotid arteries, consequently ameliorating vacuoles and rarefaction changes in the white matter.

Impairment of autoregulatory vasodilation by NAD(P)H oxidase-dependent superoxide generation during acute stage of subarachnoid hemorrhage in rat pial artery.

This study assessed the mechanism(s) by which the autoregulatory vasodilation of rat pial artery in response to acute hypotension during the acute phase of subarachnoid hemorrhage (SAH) was markedly blunted. Increased superoxide production from the cerebral vessels in response to NAD(P)H at 24 hours after SAH +NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) was inhibited by intracisternal administration of a tyrosine kinase inhibitor genistein (10 μmol/L) and Rac inhibitor Clostridium difficile toxin B (1 ng/mL) and a flavoenzyme inhibitor diphenyleneiodonium (10 μmol/L). The expression of gp91phox was enhanced by SAH + L-NAME from 12 to 24 hours, which was inhibited by genistein and toxin B, but not the p22phox. Increased membrane translocation of Rac after SAH + L-NAME was attenuated by both genistein and toxin B, whereas increased tyrosine kinase activity was blocked by genistein, but not by toxin B. The blunted autoregulatory vasodilation to acute hypotension was effectively recovered by genistein and C. difficile toxin B as well as by diphenyleneiodonium. In conclusion, SAH during acute stage causes an increase in NAD(P)H oxidase—dependent superoxide formation in cerebral vessels, which is due to activation of tyrosine phosphorylation-dependent increased expression of gp91phox mRNA and translocation of Rac protein, thereby resulting in a significant reduction of autoregulatory vasodilation.

KR-31372 inhibits KDR/Flk-1 tyrosine phosphorylation via K+ATP channel opening in its antiangiogenic effect

The aim of this study was to identify the signaling pathway of the antiangiogenesis by (2R,3R,4S)-N-cyano-N-(6-nitro-3,4-dihydro-hydroxy-2-methyl-2-dimethoxymethyl 2H-1-benzopyran-4yl)-N-benzylguanidine (KR-31372). KR-31372 inhibited the in vitro basal tube formation using Matrigel-coated plate and in vivo neovascularizations in mice induced by Matrigel containing vascular endothelial growth factor (VEGF(165), 5 ng/ml). VEGF(165) markedly increased cell proliferation using 5-bromo-2-deoxyuridine incorporation and chemotactic migration using transwell chamber in human umbilical vein endothelial cells, those of which were significantly suppressed by pretreatment with KR-31372 and levcromakalim concentration dependently. The suppression of all these variables were strongly antagonized by glibenclamide, ATP-sensitive K(+) channel blocker. KR-31372 (10(-6)-10(-4) M) and levcromakalim (10(-5) M) concentration-dependently suppressed the VEGF(165)-induced increases in KDR/Flk-1 tyrosine phosphorylation as well as the extracellular signal-related kinase 1/2 (ERK1/2), p38 MAK and p125(FAK) tyrosine phosphorylation. These variables were significantly antagonized by glibenclamide. In conclusion, KR-31372 significantly inhibited the KDR/Flk-1 tyrosine phosphorylation-linked ERK1/2, p38 MAPK and p125(FAK) tyrosine phosphorylation via mediation of K(+)(ATP) channel opening, thereby resulting in antiangiogenesis.

Effects of Polyamines on TNFalpha- or Tamoxifen-induced Apoptosis in Human Breast Cancer Cells.

PURPOSEnTo investigate the effects of polyamines on tumor necrosis factor alpha (TNFalpha)-or tamoxifen (TAM)-induced apoptosis in estrogen receptor (ER)-positive MCF- 7 and ER-negative MDA-MB-231 human breast cancer cells.nnnMATERIALS AND METHODSnCell viability was assessed by using MTT assay. Reactive oxygen species (ROS) generation was measured using 2, 7-dichlorofluorescin diacetste (DCFDA) by fluorescence plate reader. DNA fragmentation was assessed by 1.5% agarose gel electrophoresis.nnnRESULTSnTNFalpah and TAM showed significant dose- and time- dependent inhibitory effects on the growth of MCF-7 human cells. However, the growth of MDA-MB-231 cells were not inhibited by TNFalpha or TAM treatment. The generation of ROS was increased in dose-and time-dependent manner by TNFalpha treatment in MCF-7 cells. Polyamines, especially spermine suppressed TNFalpha-induced ROS generation in MCF-7 cells. Antioxidant effects of polyamines were also demonstrated by DNA fragmentation, cell morphology as well as ROS generation assay. Polyamines also blocked TAM-induced cell death in MCF-7 cell. However, MDA-MB-231 cells showed resistance to the cytotoxic effects of TNFalpha or TAM.nnnCONCLUSIONnThese results suggest that polyamines may prevent TNFalpha or TAM-induced apoptosis in MCF-7 human breast cancer cells.