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Biomedical subjects

W S Park

Publications and source records attributed to W S Park.

At least 19 recordsLinked to original sources
PubMed2006

Mutational analysis of the hCDC4 gene in gastric carcinomas.

hCDC4, a ubiquitin ligase, plays a role in the control of cell cycle and chromosome stability. The hCDC4 gene is considered a tumour suppressor gene and is mutated in several human neoplasias, including colorectal and endometrial tumours. Data on the hCDC4 mutation in gastric cancer is, however, lacking. This study explored the possibility that hCDC4 mutation is involved in the development of gastric cancer. The hCDC4 gene in 162 gastric adenocarcinoma tissues was analysed for somatic mutations using a polymerase chain reaction-single strand conformation polymorphism assay. Overall, six hCDC4 mutations were found (3.7%), comprising four missense, one frameshift deletion and one nonsense mutation(s). It is notable that the hCDC4 mutations were found in early as well as in advanced gastric carcinomas. These data indicate that hCDC4 mutation occasionally occurs in gastric carcinomas and suggest that it might play a role in the development of some gastric carcinomas.

Aged↗
PubMed2006

The JAK2 V617F mutation in de novo acute myelogenous leukemias.

A missense somatic mutation in JAK2 gene (JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly suggesting its role in the pathogenesis of myeloid disorders. As activation of JAK2 signaling is occurred in other malignancies as well, we have analysed 558 tissues from common human cancers, including colon, breast and lung carcinomas, and 143 acute adulthood leukemias by polymerase chain reaction -- single strand conformation polymorphism analysis. We found three JAK2 mutations in the 113 acute myelogenous leukemias (AMLs) (2.7%), but none in other cancers. The mutations consisted of two V617F mutations and one K607N mutation. None of the AML patients with the JAK2 V617F mutation had a history of previous hematologic disorders. This is the first report on the JAK2 gene mutation in AML, and the data indicated that the JAK2 gene mutation may not only contribute to the development of chronic myeloid disorders, but also to some AMLs.

Adult↗
PubMed2006

Ethnic characteristics of eyelashes: a comparative analysis in Asian and Caucasian females.

BACKGROUND: Despite similar biochemical composition of human hair between races, physico-morphological characteristics are not identical in different ethnic groups. Eyelashes have been investigated far less than scalp hair, and the information available is insufficient. OBJECTIVES: To obtain basic information about eyelashes and to clarify differences between female eyelashes in Asians and Caucasians. METHODS: Twenty Asian and 10 white Caucasian female volunteers aged between 20 and 29 years were admitted to the study. Lateral digital photographs of upper eyelashes were taken and curl-up and lift-up angles of upper eyelashes were measured from lateral views. Images of upper eyelashes were also taken using the phototrichogram technique and total numbers, lengths and thicknesses of upper eyelashes were obtained (a total of 4661 eyelashes; 2946 for Asian, 1715 for Caucasian). The central portion of the eyelashes or whole eyelashes were clipped and images were taken immediately and 7 days later to obtain the growth rate and anagen ratio of upper eyelashes. Numbers and thickness of eyelash cuticular layers were obtained by electron microscopy. RESULTS: Compared with Caucasians, Asian eyelashes revealed lower lift-up and curl-up angles, fewer numbers and a thicker transverse diameter. However, no statistical difference was observed in length or growth rate. Duration of anagen was estimated at about 2 months. The eyelash anagen ratio obtained from five Asians was 17.8 +/- 3.3%. By electron microscopy, the number of cuticular layers in transverse section was greater in Asian (8.0 +/- 1.2) than Caucasian females (6.5 +/- 1.1), but no statistical difference was found in single cuticle layer thickness between the two groups. Moreover, eyelash characteristics were not influenced by eye makeup in either race. CONCLUSIONS: Our results on eyelash morphology and growth characteristics demonstrated significant ethnic differences in Asian and Caucasian females that could provide basic information for future investigations.

Adult↗
PubMed2005

Quantitation of niflumic acid in human plasma by high-performance liquid chromatography with ultraviolet absorbance detection and its application to a bioequivalence study of talniflumate tablets.

A rapid and simple HPLC method with UV detection (288 nm) was developed and validated for quantitation of niflumic acid in human plasma, the active metabolite of talniflumate. After precipitation with 100% methanol containing the internal standard, indomethacin, the analysis of the niflumic acid level in the plasma samples was carried out using a reverse phase C18 CAPCELL PAK (5 microm, 4.6 mm x 250 mm) column. The chromatographic separation was accomplished with an isocratic mobile phase consisting of a mixture of 0.1M sodium acetate in water and acetonitrile (37:63, v/v), adjusted to pH 6.4. This HPLC method was validated by examining its precision and accuracy for inter- and intra-day runs in a linear concentration range of 0.02-5.00 microg/mL. Stability of niflumic acid in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days storage in a freezer. This validated method was successfully applied to the bioequivalence study of talniflunate in healthy volunteers.

Adult↗
PubMed2004

Genetic analysis of the LKB1/STK11 gene in hepatocellular carcinomas.

The tumour suppressor gene, LKB1/STK11, has been mapped to chromosome 19p13, a region showing frequent allelic loss in various human cancers, including hepatocellular carcinoma (HCC). Additionally, LKB1 physically associates with p53 and regulates p53-dependent apoptotic pathways. To investigate whether genetic alterations of LKB1 could be involved in the tumorigenesis of HCC, we analysed the genetic alterations of the LKB1 and p53 genes in seven dysplastic nodules and 80 HCCs. We found one LKB1 missense mutation, CCG-->CTG (Pro-->Leu) at codon 281 within the kinase domain. We also found allelic loss in six of 27 (22%) informative HCC cases and all of them were HBV-positive cases. In addition, we detected seven missense, one nonsense and one silent mutations (nine of 80, 11%) of p53 in HCCs only. These results suggest that genetic alterations of the LKB1 or p53 genes may play an important role in tumour development or progression of a sub-set of HCCs, and may also provide alternative mechanisms to protect the HCC cell from p53-dependent apoptosis.

AMP-Activated Protein Kinase Kinases↗
PubMed2004

Production and the characterization of monoclonal antibody against CD43, K06.

A monoclonal antibody against human CD43 has been developed and designated as K06. Its reactivity in the lymphoid organs was different from that of known anti-CD43 monoclonal antibodies suggesting that this may recognize a novel epitope of human CD43 molecule. The CD43 epitope detected by anti-K06 monoclonal antibody was highly expressed in cortical thymocytes, platelets, and myeloid cells of normal peripheral blood, and its reactivity was comparable to that of known anti-CD43 monoclonal antibodies. However, the density of this epitope was lower in the medullary thymocytes. Biochemical studies indicated that anti-K06 monoclonal antibody could recognize glycosylated moiety of CD43 antigen. The expression profile of anti-K06 monoclonal antibody in several cell lines was somewhat different from that of known anti-CD43 antibodies. In addition, CD43 ligation through the K06 epitope appeared to induce apoptosis in human leukemic cell line, Molt-4. We therefore assume that K06 epitope of human CD43 might have some role in T-cell development.

Antibodies, Monoclonal↗
PubMed2003

BRAF mutations in non-Hodgkin's lymphoma.

Ras proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. BRAF, which encodes an RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers. The activating mutation of BRAF is known to play a role in tumour development. As there have been no data on the BRAF mutation in non-Hodgkin's lymphoma (NHL), we analysed the genomic DNAs from 164 NHLs by polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) for the detection of somatic mutations of BRAF (exons 11 and 15). Overall, we detected BRAF mutations in four NHLs (2.4%). Whereas most BRAF mutations in human cancers involved V599 of BRAF, all of the four BRAF mutations in the NHLs involved other amino acids (one G468A, two G468R and one D593G). To our knowledge, this is the first report on BRAF mutation in NHL, and the data indicate that BRAF is occasionally mutated in NHL, and suggest that BRAF mutation may contribute to the tumour development in some NHLs.

Cell Transformation, Neoplastic↗
PubMed2002

The skin barrier state of aged hairless mice in a dry environment.

BACKGROUND: Many elderly people have chronic xerosis, and frequently experience an exacerbation during winter. OBJECTIVES: To investigate the barrier state of aged murine skin with or without barrier disruption in a dry environment. METHODS: Aged and young hairless mice were kept separately in dry and normal conditions for 9 days. Acetone treatment was used to perturb the skin barrier. Skin barrier function was measured as transepidermal water loss (TEWL), and morphological changes in the epidermis were studied by electron microscopy. RESULTS: The baseline TEWL was not higher in the dry environment. The number of stratum corneum (SC) layers and the epidermal thickness of aged mice increased in the dry environment. The recovery rate of the aged skin barrier was neither accelerated nor delayed in the dry environment. In the normal environment, aged mice recovered more slowly than young mice. After barrier perturbation in the aged mice, changes in SC layers and in epidermal thickness were similar in the two environments. The secretion and number of lamellar bodies did not differ between the two environments. CONCLUSIONS: We confirmed that a dry environment induces epidermal proliferation and scaling in both aged and young mice. However, no remarkable difference was found in the skin barrier recovery of aged hairless mice in a dry environment.

Acetone↗
PubMed2001

Effect of hypothermia on bilirubin-induced alterations in brain cell membrane function and energy metabolism in newborn piglets.

The aim of this study was to evaluate the effects of hypothermia on bilirubin-induced alterations in brain cell membrane function and energy metabolism in the developing brain. Thirty-seven newborn piglets were divided randomly into four groups: normothermic control (NC, n=9); hypothermic control (HC, n=7); normothermic bilirubin infusion (NB, n=11); and hypothermic bilirubin infusion (HB, n=10) groups. In bilirubin infusion groups (NB and HB), a loading dose of bilirubin (35 mg/kg) was given over 5 min, followed by a continuous infusion (25 mg/kg/h) for 4 h. The control groups (NC, HC) received a bilirubin-free buffer solution. Sulfadimethoxine was administered to animals in all experimental groups. Rectal temperature was maintained between 38.0 and 39.0 degrees C in normothermic groups, and between 34.0 and 35.0 degrees C in hypothermic groups for 4 h after the start of bilirubin infusion. The final blood and brain bilirubin concentrations in the bilirubin infusion groups (NB and HB) were not significantly different. Decreased cerebral cortical cell membrane Na(+),K(+)-ATPase activity and increased lipid peroxidation products observed in the NB group, indicative of bilirubin-induced brain damage, were significantly attenuated in the HB group. Hypothermia also significantly improved the bilirubin-induced reduction in brain ATP and phosphocreatine levels and increase in blood and brain lactate levels. In summary, hypothermia significantly attenuated the bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglet. These findings suggest the possibility that hypothermia could be a good neuroprotective therapeutic modality in neonatal bilirubin encephalopathy.

Adenosine Triphosphate↗
PubMed2001

Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers.

Several lines of evidence suggest that apoptosis dysregulation plays an important role in cancer metastasis. In this study, to explore the possibility that the mutations of death receptors are involved in the metastasis mechanism, we analyzed the death domains of Fas and tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 and -2 (TRAIL-R1 and -R2) genes for the detection of somatic mutations in 57 breast cancers with (n = 34) or without (n = 23) metastasis to the regional lymph nodes. We found seven mutations (three TRAIL-R1 and four TRAIL-R2 mutations), and these mutations were detected only in the breast cancers with metastasis. Furthermore, we also analyzed the allelic losses of chromosome 8p21-22, where TRAIL-R1 and R2 reside in the same series of breast cancers, and found that the allelic losses were significantly higher in metastatic breast cancers. We expressed the tumor-derived TRAIL-R1 and TRAIL-R2 mutants in 293 cells and found that apoptosis was suppressed. These data suggest that TRAIL-R1 and R2 genes are relevant to the frequent loss of chromosome 8p21-22 in breast cancer and that the inactivating mutations of TRAIL-R1 and -R2 genes play a role in the metastasis of breast cancer.

Apoptosis↗
PubMed2001

Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after acute transient global hypoxia-ischemia in the newborn piglet.

This study was done to determine the effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after hypoxia-ischemia (HI). Forty-five newborn piglets were divided randomly into four experimental groups: normoxia control (NC, n=9); HI/reoxygenation-reperfusion (RR) control (HC, n=11); HI/RR hyperglycemia (HE, n=12); and HI/RR hypoglycemia (HO, n=13) group. Animals were subjected to transient HI for 30 min followed by 2 h of RR. Cerebral HI was induced by temporary but complete occlusion of bilateral common carotid arteries with surgical clips and simultaneous breathing with 8% oxygen. Glucose was unregulated in HC group, and controlled by modified glucose clamp technique immediately after HI in HE (350 mg/dl) and HO (50 mg/dl) groups. During HI, heart rate, base deficit, glucose and lactate level in the blood and cerebrospinal fluid increased, and arterial pH, oxygen saturation and blood pressure decreased significantly in HC, HE and HO groups. During RR, these abnormalities returned to normal values, but lactic acidosis persisted especially in HO group. Cerebral Na(+),K(+)-ATPase activity decreased, and lipid peroxidation products increased significantly in HC group than in NC group, and these abnormalities were significantly aggravated in HE, but not in HO, group. Brain ATP and phosphocreatine levels in HE group were significantly reduced compared to the corresponding values in NC, HC and HO groups. In summary, hyperglycemia, but not hypoglycemia immediately after HI interfered with the recovery of brain cell membrane function and energy metabolism. These findings suggest that post-hypoxic-ischemic hyperglycemia is not beneficial and might even be harmful in neonatal hypoxic-ischemic encephalopathy.

Adenosine Triphosphatases↗
PubMed2001

Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma.

Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.

Humans↗
PubMed2001

CD99 regulates the transport of MHC class I molecules from the Golgi complex to the cell surface.

The down-regulation of surface expression of MHC class I molecules has recently been reported in the CD99-deficient lymphoblastoid B cell line displaying the characteristics of Hodgkin's and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surface is primarily due to a defect in the transport from the Golgi complex to the plasma membrane. Loss of CD99 did not affect the steady-state expression levels of mRNA and protein of MHC class I molecules. In addition, the assembly of MHC class I molecules and the transport from the endoplasmic reticulum to the cis-Golgi occurred normally in the CD99-deficient cells, and no difference was detected between the CD99-deficient and the control cells in the pattern and degree of endocytosis. Instead, the CD99-deficient cells displayed the delayed transport of newly synthesized MHC class I molecules to the plasma membrane, thus causing accumulation of the molecules within the cells. The accumulated MHC class I molecules in the CD99-deficient cells were colocalized with alpha-mannosidase II and gamma-adaptin in the Golgi compartment. These results suggest that CD99 may be associated with the post-Golgi trafficking machinery by regulating the transport to the plasma membrane rather than the endocytosis of surface MHC class I molecules, providing a novel mechanism of MHC class I down-regulation for immune escape.

12E7 Antigen↗
PubMed2001

Somatic mutations in the death domain of the Fas (Apo-1/CD95) gene in gastric cancer.

It is now believed that genes regulating apoptosis are also important variables in cancer development. Fas, a transmembrane protein of the tumour necrosis factor receptor family, is a key molecule for cell death signalling. The mutation of the primary structure of the Fas gene might also be one of the possible mechanisms that disrupt Fas-mediated apoptosis in tumour cells. The purpose of this study was to determine whether somatic mutation of the Fas gene could be involved in the tumourigenesis of gastric cancer. Polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) analysis with two intragenic polymorphic markers, and mutation analysis for the entire coding regions of the Fas gene were performed in 43 cases of gastric cancer, using PCR-single-strand conformational polymorphism sequencing. Five (11.6%) missense mutations were detected, only in the death domain of the Fas gene. Although these mutations were observed only in intestinal-type gastric cancers, there was no statistically significant difference in the frequency of Fas mutation between intestinal- and diffuse-type gastric cancer (p=0.068). Nine LOH out of 22 informative cases were also detected with one or both markers (41%). Three of them demonstrated a somatic mutation in the remaining allele, indicating the inactivation of both alleles. These results suggest that genetic alterations of the Fas gene may not only be limited to gastric cancer cell protection through Fas resistance, but may also play an important role in tumour promotion and/or progression in a subset of gastric cancer.

Adenocarcinoma↗