Biomedical subjects

K Park

Publications and source records attributed to K Park.

At least 199 records · Page 11Linked to original sources

PubMed1999

Synchronization and resonance in a driven system of coupled oscillators.

We study the noise effects in a driven system of globally coupled oscillators, with particular attention to the interplay between driving and noise. The self-consistency equation for the order parameter, which measures the collective synchronization of the system, is derived; it is found that the total order parameter decreases monotonically with noise, indicating overall suppression of synchronization. Still, for large coupling strengths, there exists an optimal noise level at which the periodic (ac) component of the order parameter reaches its maximum. The response of the phase velocity is also examined and found to display resonance behavior.

Journal Article↗

PubMed1999

Mechanistic aspects of green tea as a cancer preventive: effect of components on human stomach cancer cell lines.

It is now well accepted that (-)-epigallocatechin gallate (EGCG) inhibits carcinogenesis in the digestive tract in rodents. To understand the mechanisms of anticarcinogenesis, we first studied growth inhibition by EGCG in human stomach cancer cell lines established at Seoul National University (SNU cell lines). Inhibition by EGCG of [3H]thymidine incorporation into eight SNU cell lines was examined, in relation to transforming growth factor-beta (TGF-beta) responsiveness. Various tea polyphenols derived from green tea and black tea induced growth inhibition and apoptosis of human stomach cancer cell line KATO III, and inhibition of tumor necrosis factor-alpha (TNF-alpha) release from the cells, in the order of (-)-epicatechin gallate (ECG), EGCG, (-)-epigallocatechin (EGC), teaflavins (TF) and (-)-epicatechin (EC). In addition, we demonstrated that EGCG inhibited TNF-alpha gene expression in KATO III cells, as well as okadaic acid-induced AP-1 and NF-kappa B activation. The inhibitory potencies of EGCG for AP-1 and NF-kappa B binding to DNA were different between KATO III cells and mouse fibroblast cell line BALB/3T3. Thus, EGCG and other tea polyphenols may interact with various transcription factors, in addition to AP-1 and NF-kappa B, in nuclei of various cells, resulting in inhibition of TNF-alpha gene expression and TNF-alpha release.

3T3 Cells↗

PubMed1999

Expression of multiple Na+/H+ exchanger isoforms in rat parotid acinar and ductal cells.

Several members of the Na+/H+ exchanger gene family (NHE1, NHE2, NHE3, and NHE4) with unique functional properties have been cloned from rat epithelial tissues. The present study examined the molecular and pharmacological properties of Na+/H+ exchange in rat parotid salivary gland cells. In acinar cells superfused with a physiological salt solution (145 mM Na+), Na+/H+ exchanger activity was inhibited by low concentrations of the amiloride derivative ethylisopropyl amiloride (EIPA; IC50 = 0.014 +/- 0.005 microM), suggesting the expression of amiloride-sensitive isoforms NHE1 and/or NHE2. Semiquantitative RT-PCR confirmed that NHE1 transcripts are most abundant in this cell type. In contrast, the intermediate sensitivity of ductal cells to EIPA indicated that inhibitor-sensitive and -resistant Na+/H+ exchanger isoforms are coexpressed. Ductal cells were about one order of magnitude more resistant to EIPA (IC50 = 0.754 +/- 0.104 microM) than cell lines expressing NHE1 or NHE2 (IC50 = 0.076 +/- 0.013 or 0.055 +/- 0.015 microM, respectively). Conversely, ductal cells were nearly one order of magnitude more sensitive to EIPA than a cell line expressing the NHE3 isoform (IC50 = 6.25 +/- 1.89 microM). Semiquantitative RT-PCR demonstrated that both NHE1 and NHE3 transcripts are expressed in ducts. NHE1 was immunolocalized to the basolateral membranes of acinar and ductal cells, whereas NHE3 was exclusively seen in the apical membrane of ductal cells. Immunoblotting, immunolocalization, and semiquantitative RT-PCR experiments failed to detect NHE2 expression in either cell type. Taken together, our results demonstrate that NHE1 is the dominant functional Na+/H+ exchanger in the plasma membrane of rat parotid acinar cells, whereas NHE1 and NHE3 act in concert to regulate the intracellular pH of ductal cells.

Amiloride↗

PubMed1999

Surface modification with PEO-containing triblock copolymer for improved biocompatibility: in vitro and ex vivo studies.

Poly(ethylene oxide) (PEO) has been frequently used to modify biomaterial surfaces for improved biocompatibility. We have used PEO-polybutadiene-PEO triblock copolymer to graft PEO to biomaterials by gamma-irradiation for a total radiation dose of 1 Mrad. The molecular weight of PEO in the block copolymer was 5000. In vitro study showed that fibrinogen adsorption to Silastic, polyethylene, and glass was reduced by 70 to approximately 95% by PEO grafting. On the other hand, the reduction of fibrinogen adsorption was only 30% on expanded polytetrafluoroethylene (e-PTFE). In vitro platelet adhesion study showed that almost no platelets could adhere to PEO-coated Silastic, polyethylene, and glass, while numerous platelet aggregates were found on the ePTFE. The platelet adhesion in vitro corresponded to the fibrinogen adsorption. When the PEO-grafted surfaces were tested ex vivo using a series shunt in a canine model, the effect of the grafted PEO was not noticeable. Platelet deposition on ePTFE was reduced by PEO grafting from 8170 +/- 1030 to 5100 +/- 460 platelets 10(-3) microm2, but numerous thrombi were still present on the PEO-grafted surface. The numbers of platelets cumulated on Silastic, polyethylene, and glass were 100 +/- 80, 169 +/- 35, and 24 +/- 22 platelets 10(-3) microm2, respectively. This is about 35% reduction in platelet deposition by PEO grafting. While the numbers of deposited platelets were small, the decreases were not as large as those expected from the in vitro study. This may be due to a number of reasons which have to be clarified in future studies, but it appears that in vitro platelet adhesion and fibrinogen adsorption studies may not be a valuable predictor for the in vivo or ex vivo behavior of the PEO-grafted surfaces.

Adsorption↗

PubMed1999

Characterization of estrogen receptor-beta (ERbeta) messenger ribonucleic acid and protein expression in rat granulosa cells.

We have examined estrogen-responsiveness of ovarian granulosa cells by focusing on estrogen receptor (ER) expression. Estrogen responsiveness was determined by examining the effect of 17beta-estradiol (1-10 nM) on luciferase reporter activity in rat granulosa cells transfected with an ERE-luciferase construct. The results demonstrate an estrogen-induced (approximately 3-fold) increase in luciferase reporter activity, indicating that granulosa cells contain functional estrogen response element (ERE)-binding transcriptional activators. Gel mobility shift assays in combination with ER antibodies show that ERbeta is the predominant ERE-binding protein in granulosa cells. Western blotting results show that granulosa cells contain ERbeta-immunoreactive protein(s) migrating at a size substantially larger than the recombinant protein generated from the originally proposed 485 amino acid open-reading frame. This size discrepancy is not due to granulosa cell expression of ERbeta isoforms with insertions within the coding region because RT-PCR assays revealed products with sizes expected for ERbeta, ERbetaB, and delta3 isoforms. This size discrepancy appears to be due to usage of a well-conserved, upstream in-frame translation initiation codon (ATG436) leading to a 530 amino acid open reading frame. ERbeta messenger RNA (mRNA) characterization using 5'-rapid amplification of complementary DNA ends (5'-RACE) show the presence of two different (P1- and P2-) 5'-ends of rat ERbeta mRNA encoding the full-length ERbeta protein. The generation of the P2-specific exon is likely due to initiation of transcription from an alternative promoter. Both P1- and P2-specific exon-containing ERbeta mRNAs are expressed in granulosa cells, and they are rapidly down-regulated by the cAMP-mediated intracellular signaling pathway in cultured granulosa cells. Taken together, our results show that rat granulosa cells produce two different 3',5'-cAMP-regulated ERbeta mRNA species and that these mRNA species are capable of encoding the full-length ERbeta protein.

Animals↗

PubMed1999

Effects of castration and androgen replacement on erectile function in a rabbit model.

We investigated, in a rabbit model, the effects of castration and testosterone replacement on: 1) the hemodynamics of the corpus cavernosum; 2) alpha-1 adrenergic receptor protein expression; 3) neural NO synthase protein expression and activity; 4) phosphodiesterase type 5 activity; and 5) trabecular smooth muscle/connective tissue balance. One week after bilateral orchiectomy, animals were treated for 7 days with vehicle alone, testosterone, or estradiol. Intact control animals received vehicle only. Systemic arterial blood and intracavernosal pressures (ICP) were measured in each animal before and after electrical stimulation of the cavernosal nerve. Alpha1-adrenergic receptor protein expression was determined by ligand binding studies. NO synthase expression and activity were determined by Western blot analyses and conversion of L-arginine to citrulline, respectively. Phosphodiesterase type 5 activity was determined by hydrolysis of guanosine 3',5'-cyclic monophosphate (cGMP) in tissue extracts in the absence or presence of 100 nM sildenafil. Smooth muscle content was assessed by Masson's trichrome staining and computer-assisted histomorphometry. Castration significantly reduced ICP, but it did not alter systemic arterial blood pressure during stimulation of the cavernosal nerve. Testosterone, but not estradiol, treatment prevented the effects of castration and restored ICP to values similar to those obtained in intact animals. Castration reduced expression of alpha1-adrenergic receptor, and this reduction was prevented or reversed by testosterone replacement. Neural NO synthase protein expression and total activity were not altered significantly by castration or after testosterone replacement. However, phosphodiesterase type 5 activity increased in castrated animals treated with testosterone. Castration significantly reduced trabecular smooth muscle content, and this reduction was restored by testosterone (but not estradiol) treatment. The results of this study demonstrate that androgen deprivation alters the functional responses and structure of erectile tissue.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1999

Evaluation of 18F-FDG positron emission tomography in gastric and oesophageal carcinoma.

The aim of this study was to evaluate 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) in gastric and oesophageal carcinoma. 16 patients with biopsy proven oesophageal or gastric carcinoma had PET scans. Four patients had advanced disease and received palliative treatment. The remaining 12 patients were randomized to immediate surgery or neoadjuvant chemotherapy. Three patients had repeat PET scans following chemotherapy. PET detected the primary tumour in all cases including stage T1 lesions. Involved locoregional nodes (N1, N2) were not identified separately from the primary tumour. Semiquantitative analysis was performed in the form of tumour to liver activity ratios (TLR). In general, the TLR values were higher in the higher T stages, although there was only one case each of T1 and T2 lesions. PET scanning using 18F-FDG is a sensitive method for detecting primary oesophageal and gastric cancers but is limited in locoregional staging.

Adult↗

PubMed1999

Role of p53 gene mutation in tumor aggressiveness of intracranial meningiomas.

The mutations that occur in the p53 tumor suppressor gene have been studied in various human malignant tumors. However, little is known about this gene in meningiomas. To investigate the relationship and frequency of p53 gene mutations, the p53 polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and immunohistochemical study were performed on the 41 intracranial meningiomas (21 benign, 11 atypical, and 9 malignant). The higher the p53 protein expression rate, the poorer the histologic grade (9.5%, 72.7%, and 88.9% in benign, atypical and malignant meningioma, respectively) (p=0.000). The p53 protein expression rate was higher in recurrent meningioma (71.4%) than in nonrecurrent meningioma (10.5%) (p=0.002). PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232). Also, the rate was higher in recurrent menigioma (20%) than in nonrecurrent meningioma (0%) (o=0.495). Among five to eight exons of the p53 gene, the mutation was observed on exon 7 more frequently. In conclusion, p53 immunoreactivity and p53 gene mutation are closely correlated with histologic grade and histologic atypia of intracranial meningiomas. p53 gene mutation would be considered as a useful marker to detect the progression of intracranial meningiomas.

Brain Neoplasms↗

PubMed1999

c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer.

We underwent protein assay for Myc expression in 76 human gastric cancer tissues using immunohistochemistry. Expression of Myc protein was analyzed according to proliferative indices measured by flow cytometry. Levels of Myc protein expression was evaluated by correlating with biologic and clinical parameters. In 36 (47.4%) of 76 primary gastric cancers, overexpression of Myc was observed. We could observe expression of Myc protein in a significant portion of early gastric cancer (42.9%). Expression of Myc protein was demonstrated to be more frequent in poorly differentiated cancer cells (p=0.043). However, expression of Myc protein had little influence over progress or extent of the disease. Expression of Myc protein was significantly correlated with increased proliferative activity (p=0.032) and patients with high levels of Myc expression had poor disease-free survival. In a certain proportion of human gastric cancer, Myc protein may function as a regulator of cancer cell growth and expression of Myc may represent an aggressive phenotype of gastric cancer.

Adult↗

PubMed1999

99mTc-MIBI scan in mammary Pagets disease: a case report.

Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) uptake is known to be increased in breast cancer because of increased blood flow from angiogenesis and heightened metabolism. We performed a 99mTc-MIBI scan in a patient with mammary Paget's disease. The patient had underlying invasive cancer in the same side of the breast. 99mTc-MIBI scan exhibited a scintigraphic image of the uptake from the invasive cancer lesion located deeply in the breast toward the epidermis. 99mTc-MIBI showed an uptake in the deeply located invasive cancer lesion as well as nipple lesion. Especially, the delayed phase of Tc-MIBI scan demonstrated the tumor site more accurately. In conclusion, 99mTc-MIBI scan could be a useful adjunct to clinical decision making in the management of Paget's disease of the breast.

Breast Neoplasms↗

PubMed1999

Newly developing endoscopic devices--shadow optics and micromachine.

Based on the newly-developed engineering technologies, many kinds of useful equipment have been available for minimally invasive surgery. Recently the time to connect clinical needs and advanced technologies has become faster. In this article, we have summarized the recent technologies for endoscopic surgeries. Shadow optic technologies for better geometric perception using dual illumination in a conventional 2-D monitor and "Overview optics" for a panoramic view with an additional visual system are introduced. Micromachine technology is very close to practical implementation for minimally invasive surgeries. Virtual Biopsy is the one of the hottest topics for the next generation of endoscopy. Stereoscopic and volumetric vision systems are still on the way, which should overcome the irritating goggles and stereo display devices. As well as operational theater that integrates all the required equipment with a computer-based system, including voice recognition, still requires the standard protocols to connect many kinds of devices from different manufacturers.

Biopsy↗

PubMed1999

Histomorphometric analysis of age-related structural changes in human clitoral cavernosal tissue.

PURPOSE: To characterize age-associated histological changes of human clitoral cavernosal tissue and to determine whether age-related histological changes of clitoral cavernosal tissue correlate with vascular disease-related mortality. MATERIALS AND METHODS: Human clitorises were obtained from 15 fresh cadavers (age: 11 to 90 years) and from 3 patients undergoing clitoral surgery (age: 6 months to 15 years). Cross sections of the clitorises were stained with Masson's trichrome and utilized for computer assisted histomorphometric image analysis to determine the clitoral cavernosal content of smooth muscle and connective tissue. RESULTS: These studies revealed a strong link between increase in age and decreased clitoral cavernosal smooth muscle fibers. In histomorphometry, the percentage of clitoral cavernosal smooth muscle (mean +/- standard error) in an age group of 6 months to 15 years (n = 4) was 65+/-1.5, in 44 to 54 years (n = 7) was 50+/-1.2, and in 55 to 90 years (n = 7) was 37+/-1.3 (ANOVA, p = 0.0001). In the 18 tissues studied, decrease in the percentage of clitoral cavernosal smooth muscle significantly correlated with increase in age (simple regression, r = 0.61). In the age group of 44 to 90 years, clitoral cavernosal fibrosis was significantly greater in the presence of cardiovascular disease-related mortality compared with those without cardiovascular disease-related mortality. CONCLUSION: This study shows that aging women undergo histological changes in clitoral cavernosal erectile tissue. Vascular risk factors may adversely affect the structure of clitoral cavernosal tissue. These findings may be of importance in the pathophysiology of age-associated female sexual arousal disorders.

Adolescent↗

PubMed1999

Thrombogenicity of polyethylene oxide-bonded Dacron sewing ring in a mechanical heart valve.

BACKGROUND AND AIM OF THE STUDY: The aim of the study was to evaluate the effect of binding hydrophilic polyethylene oxide (PEO) onto Dacron fibers in the sewing ring of a mechanical heart valve (MHV), in terms of thrombogenicity of the prosthesis. METHODS: The study was performed in blinded fashion. Six Yorkshire-cross pigs (bodyweight 35-45 kg) were implanted with MHVs, in the mitral annulus, with the PEO-treated sewing ring. An additional five pigs implanted with identical MHVs, but with untreated sewing rings, served as controls. PEO of chain-length 10,000 Da was grafted to Dacron fibers using gamma irradiation. PEO-bonded Dacron fibers (diameter 100 microns) were used to weave the sewing ring, which was then assembled on a titanium stent (OD 25 mm). Autologous platelets were labeled with 111In-tropolone and injected intravenously (850-1250 microCi per injection) into the pigs on removal from cardiopulmonary bypass (CPB). At 20-24 h after surgery, platelet thrombi adherent to MHV components, and shed emboli trapped in the brain, lung, heart, kidneys and other organs/connective tissues were imaged using a gamma camera. The animals were killed and the amounts of thrombi adherent to MHV components and organ-trapped emboli quantified using an ionization chamber and gamma counter. RESULTS: There was no statistically significant difference in the adhesion of 111In-labeled platelets to either control sewing rings (0.08 +/- 0.06% dose) or PEO-treated rings (0.19 +/- 0.21% dose). The thrombogenicity of MHV components in both animal groups was in the ascending order: Dacron ring > Teflon pledgets > polypropylene sutures > titanium housing > pyrolytic carbon. The number of platelet-emboli trapped in the organs was not significantly different between the two groups. CONCLUSIONS: Simple modifications may not reduce platelet thrombosis or wound-healing of the sewing ring in the acute phase, at which time several complex processes are activating and inactivating platelets and coagulant factors during CPB and implantation of MHVs.

Animals↗

PubMed1998

Membrane-limited expression and regulation of Na+-H+ exchanger isoforms by P2 receptors in the rat submandibular gland duct.

1. Cell-specific reverse transcriptase-polymerase chain reaction (RT-PCR), immunolocalization and microspectrofluorometry were used to identify and localize the Na+-H+ exchanger (NHE) isoforms expressed in the submandibular gland (SMG) acinar and duct cells and their regulation by basolateral and luminal P2 receptors in the duct. 2. The molecular and immunofluorescence analysis showed that SMG acinar and duct cells expressed NHE1 in the basolateral membrane (BLM). Duct cells also expressed NHE2 and NHE3 in the luminal membrane (LM). 3. Expression of NHE3 was unequivocally established by the absence of staining in SMG from NHE3 knockout mice. NHE3 was expressed in the LM and in subluminal regions of the duct. 4. Measurement of the inhibition of NHE activity by the amiloride analogue HOE 694 (HOE) suggested expression of NHE1-like activity in the BLM and NHE2-like activity in the LM of the SMG duct. Several acute and chronic treatments tested failed to activate NHE activity with low affinity for HOE as expected for NHE3. Hence, the physiological function and role of NHE3 in the SMG duct is not clear at present. 5. Activation of P2 receptors resulted in activation of an NHE-independent, luminal H+ transport pathway that markedly and rapidly acidified the cells. This pathway could be blocked by luminal but not basolateral Ba2+. 6. Stimulation of P2U receptors expressed in the BLM activated largely NHE1-like activity, and stimulation of P2Z receptors expressed in the LM activated largely NHE2-like activity. 7. The interrelation between basolateral and luminal NHE activities and their respective regulation by P2U and P2Z receptors can be used to co-ordinate membrane transport events in the LM and BLM during active Na+ reabsorption by the SMG duct.

Adenosine Triphosphate↗

PubMed1998

Isolated human germinal center centroblasts have an intact mismatch repair system.

Ig somatic hypermutation contributes to the generation of high-affinity Abs that are essential for efficient humoral defense. The presence of multiple point mutations in rearranged Ig V genes and their immediate flanking sequences suggests that the DNA repair system may not be working properly in correcting point mutations introduced to the restricted region of Ig genes. We examined the DNA repair functions of germinal center (GC) centroblasts, which are the cells in which ongoing Ig hypermutation takes place. We found that GC centroblasts express all known components of the human DNA mismatch repair system, and that the system corrects DNA mismatches in a strand-specific manner in vitro. We conclude that general suppression of mismatch repair at the cellular level does not occur during somatic hypermutation.

B-Lymphocytes↗

PubMed1998

Requirements for and regulation of origin opening of plasmid P1.

Origin opening is essential for the initiation of DNA replication in the theta mode and requires binding of initiator proteins. Using reactivity to KMnO4 in vivo as an assay, we find that, like initiation, origin opening of the Escherichia coli plasmid P1 requires the host initiators DnaA and HU and the plasmid-encoded initiator RepA. The ability to detect opening at the P1ori in vivo allowed us to study this activity at various copy numbers in chimeric replicons. The opening was prevented when the P1ori was cloned in high copy vectors or when excess RepA binding sites (iterons) were provided in trans. However, when RepA supply was also increased, the opening was efficient. A further increase in RepA prevented opening. Replication of an incoming P1 under these conditions correlated with opening. These results demonstrate that initiation is possible even at abnormally high origin concentrations and that oversupply of RepA, relative to iterons, can prevent replication by blocking origin opening. It appears that plasmid overreplication can be prevented either by limiting RepA or by accumulating RepA at a rate higher than that of the origin.

Bacterial Proteins↗

PubMed1998

Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle.

Phosphodiesterases play an important physiological role by regulating the intracellular levels of cyclic nucleotides. In this study, we investigated the kinetic parameters of inhibition of phosphodiesterase (PDE) type 5 (EC 3.1.4.35, 3',5'-cyclic GMP phosphodiesterase) by a novel, high-affinity, selective PDE type 5 inhibitor, sildenafil, in intact cells and in soluble extracts of human clitoral corpus cavernosum smooth muscle cells. Sildenafil inhibited cGMP hydrolysis in the crude extract (Ki = 7.2 +/- 2.7) and in partially purified preparations (Ki = 9 nM) in a competitive manner, as determined by Dixon plots. Sildenafil was a more effective PDE type 5 inhibitor than zaprinast (Ki = 400.0 +/- 76.4 nM, crude extracts; 250 nM, partially purified). Stimulation of intracellular cGMP synthesis by the nitric oxide donor sodium nitroprusside resulted in a 3.3- and 2.9-fold increase in cGMP concentration in the presence of sildenafil or zaprinast, respectively, compared to sodium nitroprusside treatment alone in intact cells at physiological temperatures. These observations suggest that human clitoral corpus cavernosum smooth muscle tone may be regulated by the synthesis and release of nitric oxide and that this pathway is dependent on PDE type 5 activity.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1998

Direct binding to nucleic acids by Vpr of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a 15kDa regulatory protein packaged in the HIV-1 virion. Although the molecular mechanism of Vpr function during viral replication remains elusive, Vpr has been found to possess interesting biological activities, including cell-cycle arrest at the G2/M check point, promotion of the HIV-1 pre-integration complex for nuclear transport, and a low but significant level of transcriptional activation of a variety of viral and cellular promoters. We now present data suggesting that HIV-1 Vpr is a nucleic-acid-binding protein. This activity of Vpr was demonstrated by DNA-cellulose chromatography, antibody co-immunoprecipitation, and gel electrophoretic mobility shift assays. By mutational analysis, the C-terminal region of Vpr, which is rich in basic amino-acid residues, was shown to be critical for Vpr binding to nucleic acids. The nucleic-acid-binding activity of Vpr is consistent with several biological activities of Vpr and may provide an important clue for understanding the molecular interactions between HIV-1 and the host cells.

Amino Acid Sequence↗