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Biomedical subjects

S J Hong

Publications and source records attributed to S J Hong.

At least 19 recordsLinked to original sources

Multiple predictors of coronary restenosis after drug-eluting stent implantation in patients with diabetes.

OBJECTIVES: To identify parameters influencing the likelihood of restenosis after implantation of drug-eluting stents (DES) in patients with diabetes. METHODS: Stented patients (n = 840) with DES were retrospectively reviewed for inclusion in the study from the Multicenter PCI Database Registry. From this database, 211 (25.1%) of 840 patients with six-month angiographic follow up had diabetes. Predictors of coronary restenosis were identified with univariate and multivariate logistic regression analyses. RESULTS: Restenosis occurred in 92 of 629 (14.6%) patients without diabetes and in 44 (20.9%) of 211 patients with diabetes (p < 0.001). Multivariate parameters for predicting restenosis in the diabetic group were current smoking (odds ratio (OR) 1.923, 95% confidence interval (CI) 1.055 to 4.725, p = 0.036), higher C reactive protein concentration (OR 1.031, 95% CI 1.011 to 1.075, p = 0.043), use of the paclitaxel-eluting stent (OR 2.638, 95% CI 1.338 to 5.200, p = 0.005), longer stent length (OR 1.065, 95% CI 1.021 to 1.119, p = 0.033), smaller reference diameter before DES implantation (OR 0.501, 95% CI 0.110 to 0.965, p = 0.040), smaller reference diameter (OR 0.455, 95% CI 0.120 to 0.814, p = 0.026) and minimum lumen diameter (OR 0.447, 95% CI 0.068 to 0.876, p = 0.039) after DES implantation. CONCLUSION: Even with the introduction of DES, diabetes remains a significant predictor of coronary restenosis, especially in cases of a small baseline vessel size, small vessel size after percutaneous coronary intervention, longer stent length, use of the paclitaxel-eluting stent, current smoking and high C reactive protein concentration.

Angioplasty, Balloon↗

Topiramate stimulates glucose transport through AMP-activated protein kinase-mediated pathway in L6 skeletal muscle cells.

The use of topiramate (TPM) in the treatment of binge-eating disorder, bulimia nervosa, and antipsychotic-induced weight gain has recently increased, however, the exact molecular basis for its effects on body weight reduction and improved glucose homeostasis, is yet to be elucidated. Here we investigated the effect and signaling pathway of TPM on glucose uptake in L6 rat skeletal muscle cells, which account for >70% of glucose disposal in the body. Intriguingly, we found that TPM (10 microM) stimulated the rate of glucose uptake up to twofold increase. And TPM-stimulated glucose transport was inhibited with the overexpression of dominant-negative form of AMP-activated protein kinase (AMPK), an important mediator in glucose transport, implicating that AMPK-mediated pathway is involved. The TPM-stimulated glucose transport was blocked by SB203580, a specific inhibitor of AMPK downstream mediator, p38 mitogen-activated protein kinase (MAPK) protein. LY294002, an inhibitor of phosphatidylinositol (PI) 3-kinase, which is another crucial mediator in independent glucose transport pathway, did not inhibit TPM-stimulated glucose transport. We also found that TPM increased the phosphorylation level of AMPK and p38 MAPK, whereas no effect on the activity of PI 3-kinase of TPM, when assessed by PI 3-kinase assay, was observed. These results together suggest that TPM stimulates glucose transport, not via PI 3-kinase mediated, but via AMPK-mediated pathway in skeletal muscle cells, thereby contributing to the body weight regulation and glucose homeostasis.

AMP-Activated Protein Kinases↗

Management of malignant stricture of the esophagogastric junction with a newly designed self-expanding metal stent with an antireflux mechanism.

BACKGROUND AND STUDY AIMS: When stents are placed across the esophagogastric junction for palliative treatment of malignant strictures, they may lead to esophagogastric reflux. The aim of this study was to compare the effectiveness of a newly designed antireflux stent with that of a standard open stent and a currently available antireflux stent (Dostent) in preventing gastroesophageal reflux symptoms in patients with inoperable cancer at the esophagogastric junction. PATIENTS AND METHODS: Thirty-six consecutive patients with cancer at the esophagogastric junction were randomly assigned to undergo placement of a newly designed antireflux stent (n = 12), a Dostent (n = 12), or a standard open stent (n = 12). Technical and clinical success, dysphagia score, reflux symptoms, complications and ambulatory 24-h esophageal pH monitoring were assessed. RESULTS: The technical success rates were 100 %. After 1 week, dysphagia had improved in all patient groups ( P < 0.05), but the degree of improvement did not differ between the three groups. The DeMeester score was significantly lower in the group with the newly designed antireflux stent than in the other groups. The fraction of the total recording time during which esophageal pH was below 4 was 3.14 +/- 5.78 % using the newly designed antireflux stent, in comparison with 29.25 +/- 15.41 % in the Dostent group and 15.01 +/- 11.72 % in the standard open stent group ( P < 0.001). Fewer reflux episodes occurred with the newly designed antireflux stent than with the Dostent or standard open stent. There were no complications with any of the three stents. CONCLUSIONS: The newly designed antireflux stent is effective in relieving dysphagia caused by malignant cancer at the esophagogastric junction. The newly designed antireflux stent is significantly more effective in preventing gastroesophageal reflux than currently available antireflux stents.

Aged↗

Alteration of cyclopiazonic acid-mediated contracture of mouse diaphragm after denervation.

As a major Ca(2+) source for muscle contraction, the sarcoplasmic reticulum (SR) of skeletal muscle maintains its Ca(2+) content by uptake of myoplasmic Ca(2+) and by replenishment with extracellular Ca(2+). Since transection of motor nerve alters the functions of SR Ca(2+) pump and sarcolemma ion channels, this study explored the effect of denervation on the contracture evoked by cyclopiazonic acid (CPA), an inhibitor of SR Ca(2+) pump. In innervated hemidiaphragm, CPA elicited a bimodal elevation of muscle tone, which was dependent on extracellular Ca(2+) and differentially inhibited by pretreatment with 2-aminoethoxydiphenylborane (APB) and U73122. Activation of muscle Na(+) channels to simulate denervation-induced membrane depolarization did not change the contracture profile. After denervation for 5-14 days when the contracture induced by caffeine was not yet depressed, CPA elicited only APB-sensitive monophasic contracture. Stimulation of ATP-regulated K(+) channels with lemakalim hyperpolarized muscle membrane and attenuated CPA contracture in denervated, but not innervated, hemidiaphragm. The effects of lemakalim were antagonized by glybenclamide. It is inferred that the bimodal CPA contracture is resulted from distinct recruitments of Ca(2+) entry and that denervation alters the voltage dependence and down-regulates CPA-mediated Ca(2+) influx.

Action Potentials↗

Establishment of a capillary-cumulus model to study the selection of sperm for fertilization by the cumulus oophorus.

BACKGROUND: Spermatozoa have to traverse the cumulus oophorus before fertilization in vivo. Evidence suggests that the cumulus oophorus plays an important role in the fertilization process. We describe the establishment of a capillary-cumulus oophorus model with which to study the action of cumulus mass on the function of human spermatozoa. METHODS: Human cumulus oophorus was aspirated into a glass capillary. Spermatozoa were allowed to pass through the cumulus mass in the capillary from one end of the capillary. The spermatozoa that had traversed the mass were collected at the other end of the capillary and underwent sperm function analyses. RESULTS: Compared with those spermatozoa cultured in medium alone, spermatozoa exposed to the cumulus mass were more likely to have normal morphology, be capacitated and acrosome reacted, with a distinct motility pattern and better zona-binding capacity. CONCLUSION: A novel in vitro model for spermatozoa penetration through the cumulus oophorus was established. The model can be applied to investigate the effect of the cumulus oophorus on sperm functions.

Acrosome Reaction↗

Ion channels of Fasciola hepatica incorporated into planar lipid bilayers.

Ion channels are important target sites of anthelmintics, but little is known about those in Fasciola hepatica. In this work, we applied a planar lipid bilayer technique to characterize the properties of single ion channels in F. hepatica. Under a 200/40 mM KCl gradient, a large conductance channel of 251 pS was observed in 18% of the membranes studied. The channel was selective to K(+) over Cl(-) with a permeability ratio of K(+) to Cl(-) (PK/PCl) of 4.9. Open state probability (Po) of the channel was less than 0.5 and dependent on voltage (-60 to approximately +40 mV) and Ca(2+) (approximately 100 microM). The other two types of single channels observed in 11 and 5% of membranes, respectively, were a K(+)-permeable channel of 80 pS (PK/PCl=4.6) and a Cl(-)-permeable channel of 64 pS (PK/PCl=0.058). Open state probability of both channels showed little voltage dependence. The results indicate that distinct single channels of 60 to approximately 251 pS are present in relative abundance and, in addition, that the planar lipid bilayer technique can be a useful tool for the study of single ion channels in F. hepatica.

Animals↗

Through-the-scope double colonic stenting in the management of inoperable proximal malignant colonic obstruction: a pilot study.

BACKGROUND AND STUDY AIMS: Particularly in cases of proximal colonic obstruction, the long distance and tortuosity of the bowel make it difficult for gastroenterologists and radiologists to advance the stent to the point of the obstruction. The purpose of this study was to evaluate the clinical usefulness and efficacy in preventing stent migration and tumor ingrowth of a new self-expanding through-the-scope (TTS) double colonic stent in the palliative management of patients with inoperable proximal malignant colonic obstruction. PATIENTS AND METHODS: A total of seven patients (four men, three women; mean age 62 years, range 57 - 68) underwent placement of a newly developed through-the-scope self-expanding double colonic stent. The etiologies of the obstructions at the time of stent insertion were colonic adenocarcinoma (no previous surgical resection) in five cases and metastatic adenocarcinoma from gastric carcinoma in two. The locations of the obstructions were the ascending colon in three cases, the hepatic flexure in two, and the transverse colon in two. To prevent tumor ingrowth and stent migration, an uncovered Niti-S stent (Taewoong Medical Co., Ltd., Seoul, South Korea) was inserted into the stenotic area; a partly membrane-covered Niti-S stent was then again inserted into the stenotic area inside the uncovered Niti-S stent. RESULTS: The self-expanding TTS double colonic stents were placed in the colon in seven patients with acute malignant colonic obstruction. Double stenting was successful in traversing the lesion in six of the seven cases. In one patient, the stent was not successfully placed across the lesion due to a very acute angle at the hepatic flexure. There were no significant complications relating to the insertion, with no clinical or radiographic evidence of perforation or bleeding during or after the procedures, and there were no cases of stent migration or tumor ingrowth during the mean follow-up period of 13 months. CONCLUSIONS: Placement of these new self-expanding through-the-scope double colonic stents for the management of inoperable proximal malignant colonic obstruction is a feasible, effective, and safe form of palliative treatment for the prevention of stent migration and tumor ingrowth.

Adult↗

Management of malignant strictures of the cervical esophagus with a newly-designed self-expanding metal stent.

Recently, the use of self-expanding metal stents has become a well-established method of palliative treatment for stenotic malignant diseases in the middle and distal esophagus. However, published results on the use of self-expanding metal stents in cervical esophageal cancer are somewhat limited by a paucity of clinical details and experience. A new self-expanding esophageal metal stent with a short upper flange 0.7 cm in length was studied prospectively in order to assess its efficacy for palliative treatment. This report presents experience in three patients in whom this new stent was used in the treatment of cervical esophageal cancers. Stent placement was successful in all three patients, with no serious complications such as esophageal perforation, hemorrhage, or foreign-body sensation. All of the patients experienced rapid improvement in dysphagia and clinical symptoms. The newly designed self-expanding stent can be of value in the treatment of stenotic cervical esophageal cancer.

Aged↗

The origin of the triploid in Paragonimus westermani on the basis of variable regions in the mitochondrial DNA.

Triploid, parthenogenetic forms of the lungfluke, Paragonimus westermani, occur in Japan, Korea and China. The origin(s) of triploidy has been debated over the years. Sequences of two regions in the mitochondrial DNA, i.e. partial lrRNA (16S), and a portion of the non-coding region, were obtained from natural populations of P. westermani. All triploid individuals (Japan, Korea, China) and a single tetraploid individual (China) had identical sequences in the 16S region studied. Some sequence variation was observed among diploids, with those from Taiwan being distinct from the remainder. Both neighbour joining and parsimony trees using the 16S region placed diploid individuals from southwestern Japan close to the triploids and the tetraploid. The fragment amplified from the mitochondrial non-coding region showed dimorphism. One form (type A) consisted of 239 bp comprising two identical tracts of 70 bp separated by a tract of 93 bp. The second form (Type B) consisted of only a single 70 bp tract. All diploid individuals from Taiwan, China and Korea possessed type A, while those from Japan were polymorphic; individuals from Oita and Hyogo had type B, those from Chiba had type A, but both types were found in Mie. On the other hand, all of the triploid individuals and two tetraploid individuals possessed type B. Both the form present in the non-coding region and the 16S sequence suggest an affinity between a south-eastern group of diploid populations in Japan and the triploid form. A possible mechanism responsible for the origin of the triploid is discussed.

Animals↗

Dependence of cyclopiazonic-acid-induced muscle contractures on extracellular Ca2+.

Inhibition of Ca2+ uptake by the sarcoplasmic reticulum decreases cytosolic Ca2+ clearance and also triggers Ca2+ influx in response to Ca2+ store depletion. The role of extracellular Ca2+ in the contractures evoked by cyclo-piazonic acid (CPA) and thapsigargin (TG), Ca2+ pump inhibitors, was assessed in mouse diaphragm. At 3-100 microM, CPA elicited a rapid-onset contracture followed by a large elevation of muscle tone, which corresponded temporally to the monophasic slow contracture evoked by TG (1-30 microM). Irrespective of the differences in profiles, contractures were prevented and inhibited by the removal of extracellular Ca2+, but not by nicardipine and SK&F96365, blockers of voltage-gated (L-type) and receptor-operated Ca2+ channels. Mn2+ and Ni2+ preferentially depressed the fast-phase contracture, whereas long-term pretreatment with LY294002, U73122, and 2-aminoethoxydiphenylborance, inhibitors of phosphatidylinositol kinase, phospholipase C, and inositol trisphosphate receptors, suppressed the slow-phase contracture. When contracture was inhibited, the twitch response remained augmented and prolonged by CPA and TG, indicating that the inhibition was not due to malfunction of the contractile apparatus. For preparations incubated in Ca2+-free medium containing CPA, a monophasic fast upstroke of muscle tone developed as extracellular Ca2+ was restored. The results suggest that the bimodal contracture induced by CPA is mediated by the recruitment of distinct Mn2+- and U73122-sensitive Ca2+ entries. The ongoing two-component Ca2+ entries might merge if the muscle preparation was preconditioned with CPA in Ca2+-free medium to deplete cellular Ca2+ stores.

Animals↗

Inhibition of autonomic nerve-mediated inotropic responses in guinea pig atrium by bafilomycin A.

Neurosecretory vesicles actively accumulate neurotransmitter by consuming proton motive force generated by vacuolar H+-ATPase (V-ATPase). The effects of bafilomycin A, a macrolide antibiotic that inactivates V-ATPase, on nerve stimulation-mediated inotropic responses of the left atrium were studied to explore the role of the enzyme in the cholinergic and adrenergic neurotransmissions. On field stimulation, the contractility of paced atrium exhibited initial atropine-sensitive depression followed by propranolol-sensitive facilitation. Both the negative and positive inotropic effects were abolished by bafilomycin A. The inhibitions were irreversible and followed a similar time course and the inhibitory effects were accelerated by intense nerve stimulation. In contrast, bafilomycin A had no effect on the inotropic responses produced by muscarinic acetylcholine or alpha-adrenergic receptor agonist. Stimulation of neuronal nicotinic acetylcholine receptor also elicited biphasic changes of contractile force, which were depressed by bafilomycin A. Compared with the inhibitory effects on field stimulation, the depressions progressed slowly and incompletely. The results suggest that inhibition of V-ATPase depressed the synaptic transmissions at autonomic nerve-muscle junctions. Furthermore, bafilomycin A preferentially inhibited neurotransmitter release emanating from the immediately releasable pool.

Animals↗

A gadolinium and pH-sensitive hyperpolarization-activated cation current in acutely isolated single neurones from Fasciola hepatica.

Fasciola hepatica, a parasitic flatworm belonging to the Class Trematoda, is one of the first metazoan groups to possess a centralized nervous system. However, the electrophysiological properties of neurones in F. hepatica are largely unknown. In the present study, we acutely isolated viable neurones from F. hepatica and characterized their electrophysiological properties. A hyperpolarization-activated cation current was recorded in the cells using the whole-cell patch-clamp. The current was found to be activated slowly at membrane potentials negative to 0 mV and did not display any time-dependent inactivation. This current was reduced by 1 mM Gd3+ to the level of the leak current, while 3 mM of Cs+ had no effect. However, the current was inhibited by extracellular acidosis in the pH range 7.0-7.8, and the membrane potentials of these cells were depolarized by extracellular alkalosis in the pH range of 5.8 to 8.2. Gd3+ (1 mM), which inhibited the pH-sensitive hyperpolarization-activated cation current, also hyperpolarized the cells. In summary, we isolated single neurones from F. hepatica, and these were found to express a pH-sensitive hyperpolarization-activated cation current. This current may participate in the membrane depolarization of F. hepatica neurones during alkaline challenge.

Animals↗

F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes.

BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET) has a supplementary role in localizing recurrent sites of differentiated thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS: Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy and I-131 ablation therapy beforehand and showed negative I-131 scans on follow-up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node groups revealed metastasis. The sensitivity and specificity of FDG PET for metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical lymph nodes of differentiated thyroid carcinoma patients who showed negative I-131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.

Adult↗

Clonorchis sinensis: molecular cloning and characterization of 28-kDa glutathione S-transferase.

A 28-kDa glutathione S-transferase (Cs28GST) was purified from a Clonorchis sinensis cytosolic fraction through anion-exchange and glutathione-affinity column chromatographies. A monoclonal antibody raised against Cs28GST reacted specifically to the C. sinensis antigen among trematode proteins. A putative peptide of 212 amino residues deduced from a cDNA clone appeared homologous with 28-kDa GST of trematodes, and its secondary structural elements predicted a GSH-binding site. Recombinant Cs28GST showed GST enzyme activity with CDNB substrate and was sensitive to the model inhibitors. The recombinant Cs28GST was antigenically indistinguishable from the native form and was recognized specifically by C. sinensis-infected human sera. The Cs28GST was localized in the tegument and underlying mesenchymal tissues. It is suggested that Cs28GST may play significant physiological roles against bioreactive molecules and be a useful reagent for serodiagnosis of clonorchiasis.

Amino Acid Sequence↗

Reduction of quantal size and inhibition of neuromuscular transmission by bafilomycin A.

The energy for uphill transport of neurotransmitters into synaptic vesicles is created by bafilomycin A- and concanamycin A-sensitive vacuolar H(+)-ATPase (V-ATPase). Both blockers (at 0.1-5 microM) depressed twitch tension and induced tetanic fade of mouse diaphragm on stimulation of the phrenic nerve. Axonal impulse conduction and depolarization of motor endplate by exogenous acetylcholine were not inhibited. The IC(50)s for bafilomycin A and concanamycin A were 1.1+/-0.2 and 0.7+/-0.1 microM, respectively. Contractile response evoked by stimulation of diaphragm, muscle resting membrane potential and membrane resistance were not altered. V-ATPase blockers decreased quantal size and shifted the distribution of miniature endplate potentials (mepps) to low amplitude direction. The increase of mepp events in high KCl medium was suppressed slightly. The blockers depressed endplate potentials (epps) with IC(50)s of 0.7+/-0.2 microM (bafilomycin A) and 0.4+/-0.1 microM (concanamycin A). On high frequency stimulation, the coefficient of variance and run-down of epps were increased. The inhibitory effects on mepps and epps were irreversible and augmented by nerve stimulation. The results suggest that inhibition of V-ATPase reduces the acetylcholine content of synaptic vesicles, leading to suppression of neuromuscular transmission.

Animals↗

Molecular cloning and characterization of a mu-class glutathione S-transferase from Clonorchis sinensis.

In biliary passages, Clonorchis sinensis causes epithelial hyperplasia and is assumed to promote carcinogenesis. Glutathione S-transferase (GST) is an antioxidant enzyme involved in phase II defense in trematodes. A clone (pcsGSTM1) encoding a GST was identified by screening a C. sinensis cDNA library with a PCR-synthesized cDNA probe. The predicted amino acid sequence encoded by pcsGSTM1 cDNA had a high degree of sequence identity and folding topology similar to the mu-class GSTs. The estimated molecular mass of the protein, 26 kDa, was consistent with an expression by pcsGSTM1 cDNA. The bacterially expressed recombinant csGSTM1 protein possessed an enzymatic GST activity and conjugated GSH to reactive carbonyls of lipid peroxidation. The recombinant csGSTM1 protein did not share antigenic epitope(s) with GSTs of Fasciola hepatica, Paragonimus westermani and Schistosoma japonicum. The csGSTM1 was identified to a mu-class GST in C. sinensis.

Amino Acid Sequence↗