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Biomedical subjects

E S Park

Publications and source records attributed to E S Park.

At least 19 recordsLinked to original sources

Defining the mechanism by which IFN-beta dowregulates c-myc expression in human melanoma cells: pivotal role for human polynucleotide phosphorylase (hPNPaseold-35).

Type I interferons (IFN-alpha/-beta) are capable of suppressing c-myc mRNA expression by modulating post-transcriptional processing. However, the molecular mechanism of this phenomenon is poorly understood. We previously established that human polynucleotide phosphorylase (hPNPase(old-35)), a type I IFN-inducible 3',5' exoribonuclease involved in mRNA degradation, induces G1 cell cycle arrest and eventually apoptosis by specifically degrading c-myc mRNA. We now demonstrate a close association between IFN-beta-induced hPNPase(old-35) upregulation and c-myc downregulation in human melanoma cells. Employing stable melanoma cell clones expressing hPNPase(old-35) small inhibitory RNA, we demonstrate that hPNPase(old-35) is a key molecule coupled with IFN-beta-mediated downregulation of c-myc mRNA. Inhibition of hPNPase(old-35) or overexpression of c-myc protects melanoma cells from IFN-beta-mediated growth inhibition, emphasizing the importance of hPNPase(old-35) upregulation and consequent c-myc downregulation in IFN-beta-induced growth inhibition and apoptosis induction. In these contexts, targeted overexpression of hPNPase(old-35) might be a novel therapeutic strategy for c-myc-overexpressing and IFN-resistant tumors, such as melanomas.

Apoptosis↗

Clinical features and risk factors for striae distensae in Korean adolescents.

BACKGROUND: Despite the high prevalence of striae distensae, clinical studies are few in number, and their pathophysiology still obscure. OBJECTIVES: To determine the prevalence and clinical characteristics of striae distensae that occur in Korean adolescents, and to correlate their clinical features with family history, other dermatological conditions, and body measurements. METHODS: One hundred and fifty-seven healthy Korean students, aged 15 to 17, were studied. A questionnaire and physical examination were employed to assess the subjects' past and family history, and the distribution, clinical features and severity of striae distensae. RESULTS: Striae distensae were present in 131 subjects (83.4%). Ninety-four (88.2%) of 109 male and 37 (77.1%) of 48 female subjects were affected. The striae were white in colour in 69.5% and asymptomatic in most of the subjects. They developed at an average age of 13.8 years. Family history was present in 18 subjects (11.5%). Seborrhoea of the face was positively correlated (P < 0.035) with striae distensae, and atopic dermatitis negatively correlated (P < 0.001). In both sexes, the buttock was the most prevalent area of striae development, followed by the lower back and knee in boys and by the thigh and calf in girls. Striae were significantly more common on the thigh of girls and on the knee of boys. CONCLUSIONS: Our results indicate that striae distensae are a common skin condition that occurs early in puberty regardless of gender, and that they have a different anatomical distribution and relationship with body measurements in each gender.

Adolescent↗

Incidence of apoptosis in clone embryos and improved development by the treatment of donor somatic cells with putative apoptosis inhibitors.

This study was conducted to promote in vitro-development of clone embryos by the treatment of donor somatic cells with hemoglobin (Hb) and/or beta-mercaptoethanol (ME), based on the analysis of apoptosis after somatic cell nuclear transfer (SCNT). Prospective, randomized study was conducted and, in vitro-matured bovine oocytes and fetal fibroblasts were provided for SCNT. In the first series of experiment, embryo apoptosis after SCNT was monitored by a terminal deoxynucleotidyl transferase-mediated d-UTP nick end-labeling assay. As results, apoptosis occurred more (P < 0.05) frequently after SCNT than after in vitro-fertilization (IVF) of control treatment. Subsequently, donor somatic cells treated with Hb (1 microg/ml) and/or ME (10 microM) were provided for SCNT. Either Hb or ME greatly reduced apoptosis (0.083 +/- 0.006 vs. 0.058-0.068 +/- 0.005), while combined treatment did not. ME was more promotive than Hb; significant increases were found in morula compaction (86%), cell numbers of blastocyst (131.3 +/- 1.3 cells/blastocyst), and inner cell mass (31.9 +/- 0.8 cells/blastocyst) cell, and the ratio of inner cell mass to trophectodermal cell numbers (0.24 +/- 0.01). In conclusion, the treatment of donor somatic cells with ME or Hb could reduce apoptosis after SCNT, resulting improved preimplantation development.

Animals↗

Involvement of the protein kinase C pathway in thyrotropin-induced STAT3 activation in FRTL-5 thyroid cells.

The binding of thyrotropin (TSH) to the TSH receptor (TSHR) activates two signaling pathways: the cAMP-protein kinase A (PKA) and the protein kinase C (PKC) systems. We have recently demonstrated that TSH activates the Janus kinases (JAK)/signal transducer and activator of transcription (STAT) pathway via TSHR. This study aimed to investigate whether the cAMP/PKA or the PKC system is involved in STAT3 activation in response to TSH. Treatment with TSH activated STAT3 phosphorylation in FRTL-5 thyrocytes and human TSHR-expressing Chinese hamster ovary cells. TSH-induced STAT3 activation was inhibited by a blocking antibody directed against TSHR that was isolated from patients with primary myxoedema. Increased intracellular cAMP activated STAT3 but inhibition of PKA did not affect STAT3 activation. On the other hand, the PKC stimulant PMA induced STAT3 phosphorylation and the PKC inhibitors inhibited it. Moreover, inhibition of PKC blocked STAT3 activation induced by a stimulator of cAMP. Our data suggest that TSH activates STAT3 via TSHR and cAMP- and PKC-dependent pathways, and provide evidence that PKC may be involved in the pathway downstream from cAMP.

Animals↗

Quasicrystals and related approximant phases in Mg-Zn-Y.

As-cast microstructure of Mg-rich Mg(68)Zn(28)Y(4) has been investigated by a detailed transmission electron microscopy study. The as-cast Mg(68)Zn(28)Y(4) alloy consisted of three different types of phases: 10-20 m size primary solidification phase, dendritic phase grown from the primary phase and a eutectic structure formed at the later stage of solidification. The primary solidification phase has an icosahedral structure with a large degree of phason strain. 1/1 rhombohedral approximant phase with lattice parameters a=27.2 A and =63.43 degrees is first observed in Mg-Zn-Y system. The rhombohedral structure can be obtained by introducing phason strain in the six-dimensional face centered hyper-cubic lattice. The decagonal phase nucleates with orientation relationship with the icosahedral phase, and Mg(4)Zn(7) nucleates with orientation relationship with the decagonal phase, indicating a close structural similarity between the three phases. Gradual depletion of Y during solidification plays an important role in heterogeneous nucleation of decagonal and Mg(4)Zn(7) phases from icosahedral and decagonal phases, respectively.

Journal Article↗

T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer.

Manipulations capable of breaking host tolerance to induce tissue-specific T cell-mediated inflammation are of central importance to tumor immunotherapy and our understanding of autoimmunity. We demonstrate that androgen ablative therapy induces profuse T cell infiltration of benign glands and tumors in human prostates. T cell infiltration is readily apparent after 7-28 days of therapy and is comprised predominantly of a response by CD4+ T cells and comparatively fewer CD8+ T cells. Also, T cells within the treated prostate exhibit restricted TCR Vbeta gene usage, consistent with a local oligoclonal response. Recruitment/activation of antigen-presenting cells in treated prostate tissues may contribute to local T cell activation. The induction of T cell infiltration in prostate tissues treated with androgen ablation may have implications for the immunotherapeutic treatment of prostate cancer as well as other hormone-sensitive malignancies, including breast carcinoma.

Androgen Antagonists↗

Transdermal delivery of ketoprofen using microemulsions.

A transdermal preparation containing ketoprofen was developed using O/W microemulsion system. Of the oils tested, oleic acid was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of ketoprofen was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 3% ketoprofen, 6% oleic acid, 30% Labrasol/Cremophor RH 40 (1:1) and water. Terpenes were added to the microemulsion at the level of 5% and their effect on the skin permeation of ketoprofen from the microemulsion was evaluated. Of the four terpenes used, only limonene resulted in a powerful enhancing activity (3-fold increase over control).

Administration, Cutaneous↗

Distinct characteristic of Galpha(h) (transglutaminase II) by compartment: GTPase and transglutaminase activities.

Galpha(h) (transglutaminase II) is a bifunctional enzyme possessing transglutaminase and GTPase activities. To better understand the factors affecting these two functions of Galpha(h), we have examined the characteristics of purified Galpha(h) from membrane and cytosol. GTP binding activity of mouse heart Galpha(h) was higher in membrane than that from cytosol. Furthermore, phospholipase C-delta1 (PLC-delta1) activity and coimmunoprecipitation of Galpha(h)-coupled PLC-delta1 in the alpha(1)-adrenoceptor-Galpha(h)-PLC-delta1 complex preparations were increased by phenylephrine in the presence of membranous Galpha(h). On the other hand, transglutaminase activity of cytosolic Galpha(h) was higher than that from membrane Galpha(h). These results demonstrate that bifunctions of Galpha(h) are regulated by its localization that can reflect the cellular functions of Galpha(h).

Animals↗

Circularly permuted green fluorescent proteins engineered to sense Ca2+.

To visualize Ca(2+)-dependent protein-protein interactions in living cells by fluorescence readouts, we used a circularly permuted green fluorescent protein (cpGFP), in which the amino and carboxyl portions had been interchanged and reconnected by a short spacer between the original termini. The cpGFP was fused to calmodulin and its target peptide, M13. The chimeric protein, which we have named "pericam," was fluorescent and its spectral properties changed reversibly with the amount of Ca(2+), probably because of the interaction between calmodulin and M13 leading to an alteration of the environment surrounding the chromophore. Three types of pericam were obtained by mutating several amino acids adjacent to the chromophore. Of these, "flash-pericam" became brighter with Ca(2+), whereas "inverse-pericam" dimmed. On the other hand, "ratiometric-pericam" had an excitation wavelength changing in a Ca(2+)-dependent manner. All of the pericams expressed in HeLa cells were able to monitor free Ca(2+) dynamics, such as Ca(2+) oscillations in the cytosol and the nucleus. Ca(2+) imaging using high-speed confocal line-scanning microscopy and a flash-pericam allowed to detect the free propagation of Ca(2+) ions across the nuclear envelope. Then, free Ca(2+) concentrations in the nucleus and mitochondria were simultaneously measured by using ratiometric-pericams having appropriate localization signals, revealing that extra-mitochondrial Ca(2+) transients caused rapid changes in the concentration of mitochondrial Ca(2+). Finally, a "split-pericam" was made by deleting the linker in the flash-pericam. The Ca(2+)-dependent interaction between calmodulin and M13 in HeLa cells was monitored by the association of the two halves of GFP, neither of which was fluorescent by itself.

Calcium↗

SPIN90 (SH3 protein interacting with Nck, 90 kDa), an adaptor protein that is developmentally regulated during cardiac myocyte differentiation.

In the yeast two-hybrid screening, we have isolated a cDNA clone from a human heart library using Nck Src homology 3 (SH3) domains as bait. The full-length cDNA, which encoded 722 amino acids, was identified as a VIP54-related gene containing an SH3 domain, proline-rich motifs, a serine/threonine-rich region, and a long C-terminal hydrophobic region. We refer to this protein as SPIN90 (SH3 Protein Interacting with Nck, 90 kDa). The amino acid sequence of the SH3 domain has the highest homology with those of Fyn, Yes, and c-Src. SPIN90 was broadly expressed in human tissues; in particular, it was highly expressed in heart, brain, and skeletal muscle, and its expression was developmentally regulated during cardiac myocyte differentiation. SPIN90 is able to bind to the first and third SH3 domains of Nck, in vitro, and is colocalized with Nck at sarcomere Z-discs within cardiac myocytes. Moreover, treatment with antisera raised against SPIN90 disrupted sarcomere structure, suggesting that this protein may play an important role in the maintenance of sarcomere structure and/or in the assembly of myofibrils into sarcomeres.

Adaptor Proteins, Signal Transducing↗

Effects of adhesives and permeation enhancers on the skin permeation of captopril.

To formulate a transdermal drug delivery system of captopril, monolithic adhesive matrix type patches containing 20% captopril, different pressure-sensitive adhesives, and various permeation enhancers were prepared using a labcoater. The effects of the adhesives and permeation enhancers on skin permeation of captopril from the prepared patches were evaluated using Franz diffusion cells fitted with excised rat skins. The permeation rate of the drug through the excised skin was dependent on the type of polyacrylate copolymers studied. Fatty alcohols resulted in a pronounced enhancing effect on the skin permeation of captopril, while dimethyl sulfoxide, N-methyl-2-pyrrolidone, oleic acid, Transcutol, and polysorbate 20 showed no significant enhancing effect. The permeation-enhancing effect of the fatty alcohols reached the maximum at the level of 100%. Based on these results, a captopril patch may be developed with further optimization.

Acrylates↗

Hepatocellular carcinoma: correlation between vascular endothelial growth factor level and degree of enhancement by multiphase contrast-enhanced computed tomography.

RATIONALE AND OBJECTIVES: To determine whether vascular endothelial growth factor (VEGF) is a histopathological factor influencing contrast enhancement of hepatocellular carcinoma (HCC) on computed tomography (CT). METHODS: Twenty-two nodular HCCs underwent multiphase helical CT and surgery. Tumor size, histological grading of differentiation, and type of hepatitis were evaluated. Tumor attenuation was graded as hyperattenuated, isoattenuated, and hypoattenuated. Immunohistochemical staining with anti-VEGF antibody was performed and scored as weak, intermediate, or strong. Spearman's rank correlation test was used. RESULTS: Tumors ranged from 1.0 to 12.0 cm (mean 5.1 cm). The degree of enhancement during the hepatic arterial phase was significantly correlated with VEGF expression. Size was negatively correlated with VEGF expression and the degree of enhancement, but histological grade and type of hepatitis were not correlated with VEGF expression, tumor size, or degree of enhancement. CONCLUSIONS: In HCC, VEGF expression is correlated with the degree of contrast enhancement during arterial-phase CT.

Adult↗

The effect of electrical stimulation on the trunk control in young children with spastic diplegic cerebral palsy.

This study was designed to determine the effectiveness of electrical stimulation over the trunk in improving sitting balance in young children with spastic diplegic cerebral palsy who displayed poor trunk control. The subjects ranged in age from 8 to 16 months and were randomly assigned to two groups. Both group had physical therapy for 6 weeks. Electrical stimulation (ES) group had additional electrical stimulation over the abdomen and posterior back muscles. Radiographic studies were carried out on the whole spine while they were sitting before and after treatment. Kyphotic angle, Cobb's angle and lumbo-sacral angle were measured. Additionally, sitting score-Gross Motor Function Measure (GMFM) was also evaluated. There was no difference of these values at initial evaluation between the two groups. Following 6 weeks of intensive therapy, the changes of kyphotic angle and sitting score-GMFM were significantly higher in ES group statistically when compared with those of the control group. The Cobb's angle following treatment was improved in ES group, but not statistically compared with that of control group. This study suggests that electrical stimulation over the trunk become a beneficial therapeutic technique in improving the sitting posture and trunk control in young children with spastic diplegic cerebral palsy.

Cerebral Palsy↗

Comparison of anterior and posterior walkers with respect to gait parameters and energy expenditure of children with spastic diplegic cerebral palsy.

The purpose of this study was to compare gait pattern and energy consumption in children with spastic diplegic cerebral palsy, when using anterior and posterior walkers, and to determine which walker should be recommended as a walking aid for these children. Ten spastic diplegic cerebral palsied children, of average age 9 years, were enrolled in this study. Before assessment, they had all received a practice period of 1-month to familiarize themselves with both types of walker. Gait characteristics were evaluated by computer-based kinematic gait analysis using Vicon 370 Motion Analysis, and energy expenditure was determined by KBI-C while they were using the walkers. The oxygen consumption rate was significantly lower whilst using the posterior walker, as was the oxygen cost. Walking velocity and cadence on gait analysis showed no significant difference between the walker types. However, step length, single support time and double support time were significantly different for the two walkers. Flexion angles of the trunk, hip and knee were lower using a posterior walker. Gait analysis data and oxygen consumption measurements indicated that the posterior walker has more advantages in terms of upright positioning and energy conservation than the anterior walker.

Biomechanical Phenomena↗

Enhancing effect of polyoxyethylene alkyl ethers on the skin permeation of ibuprofen.

The influence of polyethoxylated non-ionic surfactants on the transport of ibuprofen across rat skin was investigated. The skin permeation of ibuprofen from a series of 17 polyoxyethylene (POE) alkyl ethers containing 5% ibuprofen was determined using Franz diffusion cells fitted with excised rat skins. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were performed for the physicochemical characterization of ibuprofen-surfactant interaction. In vitro transdermal flux through excised rat skin was found in the decreasing order of POE(5)cetyl/oleyl ether (110.24 microg/cm(2)/h)>POE(2)lauryl ether (99.91 microg/cm(2)/h)>POE(2)oleyl ether (67.46 microg/cm(2)/h)>POE(10)stearyl ether (66.19 microg/cm(2)/h). POE(2)oleyl ether showed the longest lag time (2.47 h). The enhancers containing the EO chain length of 2-5, HLB value of 7-9 and an alkyl chain length of C16-C18 were effective promoters of ibuprofen flux. FT-IR and DSC studies to probe the nature of the interaction between the ibuprofen and surfactant indicated that the hydrogen bonding state of ibuprofen was changed from the dimeric form to the carbonyl-hydroxyl (C=O-HO) hydrogen bond form in the presence of excess POE alkyl ether. These results indicated that this new system may be used in developing a transdermal formulation with improved skin permeation of ibuprofen.

Algorithms↗

Role of peroxiredoxins in regulating intracellular hydrogen peroxide and hydrogen peroxide-induced apoptosis in thyroid cells.

Peroxiredoxins (Prxs) play an important role in regulating cellular differentiation and proliferation in several types of mammalian cells. One mechanism for this action involves modulation of hydrogen peroxide (H(2)O(2))-mediated cellular responses. This report examines the expression of Prx I and Prx II in thyroid cells and their roles in eliminating H(2)O(2) produced in response to thyrotropin (TSH). Prx I and Prx II are constitutively expressed in FRTL-5 thyroid cells. Prx I expression, but not Prx II expression, is stimulated by exposure to TSH and H(2)O(2). In addition, methimazole induces a high level of Prx I mRNA and protein in these cells. Overexpression of Prx I and Prx II enhances the elimination of H(2)O(2) produced by TSH in FRTL-5 cells. Treatment with 500 micrometer H(2)O(2) causes apoptosis in FRTL-5 cells as evidenced by standard assays of apoptosis (i.e. terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end labeling, BAX expression, and poly(ADP-ribose) polymerase cleavage. Overexpression of Prx I and Prx II reduces the amount of H(2)O(2)-induced apoptosis measured by these assays. These results suggest that Prx I and Prx II are involved in the removal of H(2)O(2) in thyroid cells and can protect these cells from undergoing apoptosis. These proteins are likely to be involved in the normal physiological response to TSH-induced production of H(2)O(2) in thyroid cells.

Animals↗