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Biomedical subjects

Y C Park

Publications and source records attributed to Y C Park.

At least 19 recordsLinked to original sources
PubMed2005

Phospho-ser 15-p53 translocates into mitochondria and interacts with Bcl-2 and Bcl-xL in eugenol-induced apoptosis.

Our previous studies demonstrated that antiallergic effects of herbs such as clove and Magnoliae Flos (MF) resulted from the induction of apoptosis in mast cells. We here examined whether the antiallergic activity was caused by eugenol (4-allyl-2-methoxyphenol) which was one of major ingredients in the essential oils or extracts of numerous plants including clove and Magnoliae Flos. RBL-2H3 cells were treated with eugenol, and DNA electrophoresis, Western blotting, immunocytochemistry, confocal microscopy and immunoprecipitation were conducted. Effect of eugenol was tested using a rat anaphylaxis model. RBL-2H3 cells treated with eugenol showed typical apoptotic manifestations and translocation of p53 into mitochondria. Antisense p53 partially prevented the induction of apoptosis. Noticeably, we observed that p53 translocated into mitochondria was phosphorylated on ser 15. Phospho-ser 15-p53 physically interacted with Bcl-2 and Bcl-xL in mitochondria and its translocation into mitochondria preceded cytochrome c release and mitochondrial membrane potential (MMP) reduction. We also depicted that the survival of animals even after administration of the fatal dose of compound 48/80 might result from the decreased number of mast cells by eugenol pretreatment. In conclusion, eugenol induces apoptosis in mast cells via translocation of phospho-ser 15-p53 into mitochondria.

Animals↗
PubMed2004

Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer.

PURPOSE: To determine whether R115777 improves survival in patients with refractory advanced colorectal cancer (CRC) in a multicenter, double-blind, prospective randomized study. PATIENTS AND METHODS: Three hundred sixty-eight patients were randomly assigned to R115777 (300 mg twice daily) orally for 21 days every 28 days or placebo in a 2:1 ratio. All patients received best supportive care. The primary end point was overall survival; secondary end points were progression free survival, tumor response, toxicity, and quality of life. RESULTS: The two treatment groups were well balanced for baseline demographics, including previous chemotherapy for advanced CRC. The median overall survival for R115777 was 174 days (95% CI, 157 to 198 days), and 185 days (95% CI, 158 to 238 days) for those patients receiving placebo (P =.376). One patient achieved a partial response in the R115777 arm. Stable disease (> 3 months) was observed in 24.3% patients in the R115777 group compared to 12.8% in the placebo arm. This did not translate into a statistically significant increase in progression-free survival. Overall, treatment was well tolerated. There was an increased incidence of reversible myelosuppression (neutropenia, thrombocytopenia), rash, and grade 1 to 2 diarrhea in the R115777 arm. There was no statistically significant difference in quality of life between arms. CONCLUSION: Single agent R115777, given at this dose and schedule, has an acceptable toxicity profile, but does not improve overall survival compared to best supportive care alone in refractory advanced CRC.

Adult↗
PubMed2003

Expression of an artificial polypeptide with a repeated tripeptide glutamyl-tryptophanyl-lysine in Saccharomyces cerevisiae.

AIMS: Artificial genes, which encode 48 or 64 repeats of a tripeptide, glutamyl-tryptophanyl-lysine have been cloned to the yeast expression vector pAM82 containing the PHO5 promoter and expressed in Saccharomyces cerevisiae AH22. METHODS AND RESULTS: When the yeast cells harbouring recombinant plasmids pALTG6-2 and pALTG4-4 were derepressed in Burkholder minimal medium (Toh-e, A., Ueda, Y., Kakimoto, S.I. and Oshima, Y. (1973) Journal of Bacteriology113, 727-738) containing low phosphate (0.03 g l-1 KH2PO4 and 1.5 g l-1 KCl), the expression was the highest after 24 h induction and the artificial polypeptides were synthesized to about 10% (pALTG6-2) and 14% (pALTG4-4) of the total cell protein. CONCLUSIONS: The artificial polypeptides produced in yeast were made to react with the rabbit antiserum against the polypeptide purified from Escherichia coli and found only in the pellet fraction of cell lysates, indicating the formation of inclusion body. Artificial polypeptide consisting of Glu-Trp-Lys may be useful as partial supplement in food and feeds. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of single cell enriched with homopolymers of an essential amino acid in yeast might be an important tool of supplementing cereal diets and feed grain rations and could be used as means for improvement of the amino acid profile of single cell protein and production of pharmaceutical peptides.

Amino Acids, Essential↗
PubMed2002

A new enzymic method for the isolation and culture of human bladder body smooth muscle cells.

Cultured cells of the human urinary bladder smooth muscle are useful for investigating bladder function, but methods for culturing them are not well developed. We have now established a novel enzymic technique. The smooth muscle layer was separated out and incubated with 0.2% trypsin for 30 min at 37 degrees C. The samples were then minced and incubated with 0.1% collagenase for 30 min and centrifuged at 900 g. The pellets were resuspended in RPMI-1640 medium containing 10% fetal calf serum (FCS) and centrifuged at 250 g. The smooth muscle cells from the supernatant were cultured in RPMI-1640 containing 10% FCS. The cells grew to confluence after 7-10 days, forming the "hills and valleys" growth pattern characteristic of smooth muscle cells. Immunostaining with anti-alpha-actin, anti-myosin, and anti-caldesmon antibodies demonstrated that 99% of the cells were smooth muscle cells. To investigate the pharmacological properties of the cultured cells, we determined the inhibitory effect of muscarinic receptor antagonists on the binding of [3H]N-methylscopolamine to membranes from cultured cells. The pKi values obtained for six antagonists agreed with the corresponding values for transfected cells expressing the human muscarinic M2 subtype. Furthermore, carbachol produced an increase in the concentration of cytoplasmic free Ca2+ an action that was blocked by 4-diphenylacetoxy-N-methylpiperidine methiodide, an M3 selective antagonist. This result suggests that these cells express functional M3 muscarinic receptors, in addition to M2 receptors. The subcultured cells therefore appear to be unaffected by our new isolation method.

Calcium↗
PubMed2002

Partial outlet obstruction of the rat bladder induces a stimulatory response on proliferation of the bladder smooth muscle cells.

Outlet obstruction of the rat bladder induces hypertrophy/hyperplasia characterized by increases in bladder mass, smooth muscle content, and collagen deposition. In order to understand the mechanism of the outlet obstruction-induced hypertrophy and hyperplasia, we first determined the temporal pattern of changes in bladder mass after inducing the outlet obstruction. Histological analysis revealed that the smooth muscle cells with hypertrophy and hyperplasia, fibroblasts and connective tissue were increased in a time-dependent manner, corresponding to the temporal pattern observed in the changes in bladder mass, although the phase of changes in these tissue components was somewhat different. In order to further determine whether any proliferation-stimulatory factors were released from the bladder with obstruction in correspondence with increased bladder mass, soluble fractions were prepared from the bladders with outlet obstruction for 3-30 weeks, and their effects on proliferation of smooth muscle cells were examined. The soluble fractions prepared from the bladders at 3 to 14 weeks after obstruction slightly but significantly facilitated the proliferation of cultured smooth muscle cells, while the soluble fractions released after 20 weeks rather suppressed the proliferation. These results suggest that the initial increase in bladder mass might be in part due to the facilitated proliferation of smooth muscle cells of the bladder body induced by growth factors released into the soluble fractions, and that hypertrophy might then play a role in the increased bladder mass at later phases.

Animals↗
PubMed2002

Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis.

The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS) production, whereas the DNA repair enzyme and transcriptional regulator redox factor-1 (ref-1) protects against cell death due to oxidative stimuli. However, the function of ref-1 in regulating intracellular oxidative stress, particularly that induced by rac1, has not been defined. We examined the role of ref-1 in vascular endothelial cell oxidative stress and apoptosis. Ref-1 was expressed in both the cytoplasm and nuclei of resting endothelial cells. Cytoplasmic ref-1 translocated to the nucleus with the oxidative trigger hypoxia/reoxygenation (H/R). Forced cytoplasmic overexpression of ref-1 suppressed H/R-induced oxidative stress (H(2)O(2) production), NF-kappaB activation, and apoptosis, and also mitigated rac1-regulated H(2)O(2) production and NF-kappaB transcriptional activity. We conclude that inhibition of oxidative stress is another mechanism by which ref-1 protects against apoptosis, and that this is achieved through modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel extra-nuclear function of ref-1.

Adenoviridae↗
PubMed2001

Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain.

The inhibitor of apoptosis proteins (IAPs) represent the only endogenous caspase inhibitors and are characterized by the presence of baculoviral IAP repeats (BIRs). Here, we report the crystal structure of the complex between human caspase-7 and XIAP (BIR2 and the proceeding linker). The structure surprisingly reveals that the linker is the only contacting element for the caspase, while the BIR2 domain is invisible in the crystal. The linker interacts with and blocks the substrate groove of the caspase in a backward fashion, distinct from substrate recognition. Structural analyses suggest that the linker is the energetic and specificity determinant of the interaction. Further biochemical characterizations clearly establish that the linker harbors the major energetic determinant, while the BIR2 domain serves as a regulatory element for caspase binding and Smac neutralization.

Apoptosis Regulatory Proteins↗
PubMed2001

Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.

PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.

Adult↗
PubMed2001

Bilateral sudden deafness as a prodrome of anterior inferior cerebellar artery infarction.

BACKGROUND: Acute ischemic stroke in the distribution of the anterior inferior cerebellar artery is known to be associated with hearing loss, facial weakness, ataxia, nystagmus, and hypalgesia. There have been few reports on bilateral deafness and vertebrobasilar occlusive disease. Furthermore, previous reports have not emphasized the inner ear as a localization of bilateral deafness. OBJECTIVE: To describe the presentation of acute ischemic stroke in the distribution of the anterior inferior cerebellar artery as sudden bilateral hearing loss with minimal associated signs. DESIGN AND SETTING: Case report and tertiary care hospital. PATIENT: A 66-year-old man with diabetes mellitus developed sudden bilateral deafness, unilateral tinnitus, and vertigo 7 days before the onset of dysarthria, facial weakness, and ataxia. T2-weighted magnetic resonance imaging scans showed hyperintensities in the right lateral pons and right middle cerebral peduncle and a possible abnormality of the left middle cerebellar peduncle. A magnetic resonance angiogram showed moderately severe stenosis of the distal vertebral artery and middle third of the basilar artery. The patient's right limb coordination and gait improved steadily over several weeks, but there was no improvement in hearing in his right ear. CONCLUSIONS: The relatively isolated onset of deafness as well as the severity and persistence of the hearing loss led us to conclude that the hearing loss in this case was likely due to prominent hypoperfusion of the internal auditory artery, with labyrinthine infarction as the earliest event. Vertebrobasilar occlusive disease should be considered in the differential diagnosis of sudden bilateral deafness.

Aged↗
PubMed2001

Distribution and hydrodynamic model of the Keumdong oil spill in Kwangyang Bay, Korea.

Oil concentrations in the seawater, seabed sediments, and shoreline sediments were measured from the samples collected 165 days after the Keumdong oil spill accident, which had occurred in Kwangyang Bay of the South Sea, Korea in September 1993. Distribution patterns of the concentrations in the seabed and shoreline sediments have allowed us to hindcast the transport and fate of the spilled oil. Overall, the patterns agree better with the southward (seaward) surface water circulation than with the northward (landward) bottom water circulation over the region. Rapid, initial dispersal of the spilled oil to the south and its subsequent grounding onto the intertidal seabed sediments, as well as onto the shorelines, appear to have made ineffective the subsurface oil transport by the bottom current.

Environmental Monitoring↗
PubMed2001

Identification of muscarinic receptor subtypes of cultured smooth muscle cells and tissue of human bladder body.

BACKGROUND: Muscarinic receptor subtypes of cultured smooth muscle cells from the human bladder body were investigated by the receptor binding assay method. The result was compared with that obtained from the human bladder body tissue to confirm whether the receptor subtypes of the cells are not changed after several passages of cell culture. METHODS: Inhibitory effects of various muscarinic antagonists on the binding of [3H]-N-methylscopolamine ([3H]-NMS) to membrane preparations obtained from cultured smooth muscle cells from the fourth subculture of the human bladder body were compared with those prepared from the human bladder body tissue and cells expressing human muscarinic receptor subtypes. RESULTS: Binding-inhibition constants (pKi) for atropine, pirenzepine, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), oxybutynin and propiverine obtained from membrane preparations of cultured smooth muscle cells were 8.91, 6.35, 8.24, 8.53, 7.29 and 5.61, respectively. pKi values of these muscarinic receptor antagonists against the membrane preparation of human bladder body tissue were 9.08, 6.66, 8.05, 8.79, 7.53 and 6.04, respectively. pKi values of cultured smooth muscle cells and tissue from human bladder body were correlated closely with those of insect cells expressing the cloned human M2 receptor subtype. CONCLUSION: The binding affinities for various muscarinic receptor antagonists of cultured human smooth muscle cells were maintained through the fourth subculture and it was suggested that the M2 receptor subtype is predominantly expressed in cultured smooth muscle cells of human bladder body as well as in tissue of the human bladder body.

Cells, Cultured↗
PubMed2001

Cephalometric and physiologic predictors of the efficacy of an adjustable oral appliance for treating obstructive sleep apnea.

The purpose of this study was to investigate whether any physiologic or cephalometric parameters could be used to predict the efficacy of an adjustable mandibular advancement appliance for treating obstructive sleep apnea (OSA). Forty-two male and 5 female patients with OSA were recruited on the basis of baseline polysomnography with a documented Apnea and Hypopnea Index (AHI) greater than 15 per hour. Repeat polysomnography was performed with the appliance in place. Baseline cephalometry was performed for each patient, and follow-up cephalometry was completed for 19 of the subjects. The subjects were divided into 3 groups on the basis of the degree of change in the AHI with oral appliance therapy: good response (> 75% decrease in AHI), moderate response (25% to 75% decrease in AHI), and poor response (< 25% decrease in AHI). Patients with a good response were younger and had smaller upper airways. In a linear regression analysis, the change in AHI (%) was associated with physiologic (age and body mass index), cephalometric (overjet, height of the maxillary molars, vertical height of the hyoid bone), and airway variables. However, changes in either overbite or overjet were not related to changes in any of the polysomnographic variables for the 19 subjects. A stepwise regression analysis revealed a better treatment response with the adjustable mandibular advancement appliance in patients who were younger and had a lower body mass index, a longer maxilla, a smaller oropharynx, a smaller overjet, less erupted maxillary molars, and a larger ratio of vertical airway length to the cross-sectional area of the soft palate.

Adult↗
PubMed2001

Schizophrenic delusions in Seoul, Shanghai and Taipei: a transcultural study.

In this transcultural study of schizophrenic delusions among patients in Seoul, Shanghai and Taipei, we discovered that both the frequency and content of delusions differed among the three groups; and that these differences could perhaps be explained by varying sociocultural and political situations. Delusional themes that are sensitive to sociocultural or political situations include guilt, love/sex, religion, somatic damage, economy/business and politics. Delusions regarding longevity, love/sex, dysmorphophobia/dysosmophobia, religion or supernatural matters, and espionage/spy stories were most frequent in Seoul patients. Those in Taipei predominantly had delusions about possession, religion or supernatural matters, hypnotism, and mass media/computers. Shanghai patients often had delusions of poisons, being prickled by poisoned needles, their brain and viscera extracted and being a family member of political authorities.

Adult↗
PubMed2001

Results of neurilemoma treatment: a review of 78 cases.

Between 1984 and 1994, a total of 78 patients underwent surgery for neurilemoma of the trunk or extremities. The incidence according to the involved nerve was analyzed and the follow-up results and complications after surgical treatment were reviewed. The median nerve was most frequently involved among 15 different nerves. Marginal excision was performed in 70 (90%) patients, incisional biopsy in 6 (8%), and wide excision in 2 (2%). Postoperative complications were paresthesia in 7 patients. There was no recurrence or malignant transformation until the average 47 months of follow-up. In most patients, marginal excision was sufficient to prevent local recurrence and did not impair nerve function significantly.

Adolescent↗
PubMed2001

[A case of squamous cell carcinoma of the bladder that was successfully treated with multidisciplinary therapies].

A 45-year-old man with hematopyuria detected at another hospital visited our department for further examination. Endoscopic examination revealed a disintegration abscess between the bladder neck and prostatic urethra. Transurethral biopsy demonstrated squamous cell carcinoma of the bladder. He received 40 Gy of radiation combined with M-VAC (methotrexate, vinblastine, dovorubicin cisplatin) chemotherapy. Pathologically, a complete response was found when he underwent total cystourethrectomy. There has been no sign of recurrence for one and a half years postoperatively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Effects of isoproterenol and butylscopolamine on the friction between an artificial stone and the intraureteral wall in anesthetized rabbits.

PURPOSE: We evaluated the effects of the nonselective beta-adrenoceptor agonist isoproterenol and the nonselective muscarinic antagonist butylscopolamine on ureteral wall tension, namely friction between an artificial stone and the intraureteral wall, in anesthetized rabbits. MATERIALS AND METHODS: The relaxing effect of the drugs on the KCl induced tonic contraction was examined in isolated rabbit ureters. The effect of the drugs on the applied force needed for the artificial stone to pass at a constant speed through the ureter, called sliding force, was evaluated in anesthetized rabbits. RESULTS: In a concentration dependent manner isoproterenol but not butylscopolamine reduced the KCl induced contraction in isolated ureter (mean pD2 7.35 +/- 0.06). Intravenous administration of 1 and 10 microg./kg. isoproterenol significantly decreased the friction between the artificial stone and intraureteral wall in anesthetized rabbits with sliding force at 15 minutes after drug administration decreased by 54.5% and 63.6%, respectively. In contrast, 100 and 1,000 microg./kg. butylscopolamine intravenously had no evident effect on ureteral wall tension. CONCLUSIONS: Our results strongly suggest that ureteral smooth muscle relaxation by beta-adrenergic stimulation reduces ureteral wall tension, thereby, diminishing mechanical effects impeding the movement of a ureteral stone down the ureter.

Adrenergic beta-Agonists↗