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Biomedical subjects

K Y Lee

Publications and source records attributed to K Y Lee.

At least 37 records · Page 2Linked to original sources

Alteration of biochemical profiles after high-dose intravenous immunoglobulin administration in Kawasaki disease.

UNLABELLED: Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory treatment for several immune-mediated diseases. Early effects of high-dose IVIG treatment on biochemical profiles including lipids and proteins were evaluated in patients with Kawasaki disease (KD). Twelve children with KD (9 boys) were treated with IVIG at 2 g/kg over a period of 12 h. Serial sera samples were collected from the patients four times: before IVIG treatment and 2 h, 24 h and 7 d after IVIG treatment. The samples were frozen at -20 degrees C before biochemical analysis. A significant decrease in albumin concentration was found 2 h and 24 h after IVIG treatment, but this recovered to the pretreatment level after 7 d. Total cholesterol and triglyceride increased slightly after 7 d. A significant decrease in HDL-cholesterol and C-reactive protein was seen 2 h and 24 h after IVIG treatment. CONCLUSION: High-dose IVIG affects immediate changes in protein profiles and HDL-cholesterol in KD. Changes in HDL-cholesterol induced by IVIG may be the result of changes in systemic protein metabolism.

C-Reactive Protein↗

Localization of Claude's syndrome.

Although the red nucleus often has been suggested to be the lesion site responsible for Claude's syndrome, the precise localization of the syndrome is uncertain. Lesion sites were reviewed in six patients with Claude's syndrome and compared with other patients with the syndrome identified by a literature search. The findings strongly suggest that Claude's syndrome occurs because of a lesion of the superior cerebellar peduncle just below and medial to the red nucleus. Midbrain infarction and partial oculomotor nerve palsy was common.

Adult↗

Differential and cell-type specific microheterogeneity of high mannose-type Asn-linked oligosaccharides of human transferrin receptor.

The structural analysis of high mannose-type Asn-linked (N-linked) oligosaccharides of the human transferrin receptor (hTR) from D-[2-3H]mannose metabolic-radiolabeled human cells--A431, K562, BeWo, and HL60--was investigated. The radiolabeled hTR glycopeptides were prepared and fractionated by a lectin chromatography of Concanavalin A-Sepharose. The composition analysis of hTR glycopeptides revealed that Con A-I contains both mannose and fucose, whereas Con A-III has mannose exclusively. The Con A-III glycopeptides were treated with Endo H. The released oligosaccharides were charge-fractionated by QAE-Sephadex. The neutral oligosaccharides were further size-fractionated by an amine absorption high performance liquid chromatography (HPLC). Our results demonstrate that the high mannose-type oligosaccharides of hTR ranged in size from Man5-R to Man9-R with cell-type specific patterns. A relative amount of each component was found to be differentially heterogeneous among the four different human cell lines.

Asparagine↗

Transcriptional regulation of the estrogen-inducible pS2 breast cancer marker gene by the ERR family of orphan nuclear receptors.

The estrogen-receptor-related receptors (ERRs) alpha, beta, and gamma are orphan nuclear hormone receptors that share significant homology with the estrogen receptors (ERs) but are not activated by natural estrogens. In contrast, the ERRs display constitutive transcriptional activity in the absence of exogenously added ligand. However, the ERRs bind to the estrogen response element and to the extended half-sites of which a subset can also be recognized by ERalpha, suggesting that ERRs and ERs may control overlapping regulatory pathways. To test this hypothesis, we explored the possibility that ERRs could regulate the expression of the estrogen-inducible pS2 gene, a human breast cancer prognostic marker. Transfection studies show that all of the ERR isoforms can activate the pS2 promoter in a variety of cell types, including breast cancer cell lines. Surprisingly, sequence analysis combined with mutational studies revealed that, in addition to the well-characterized estrogen response element, the presence of a functional extended half-site within the pS2 promoter is also required for complete response to both ER and ERR pathways. We show that ERR transcriptional activity on the pS2 promoter is considerably enhanced in the presence of all three members of the steroid receptor coactivator family but is completely abolished on treatment with the synthetic estrogen diethylstilbestrol, a recently described inhibitor of ERR function. Finally, we demonstrate that ERRalpha is the major isoform expressed in human breast cancer cell lines and that diethylstilbestrol can inhibit the growth of both ER-positive and -negative cell lines. Taken together, these results demonstrate that estrogen-inducible genes such as pS2 can be ERR targets and suggest that pharmacological modulation of ERRalpha activity may have therapeutic value in the treatment of breast cancer.

Animals↗

Rescue treatment with abciximab in acute ischemic stroke.

In acute ischemic stroke, reocclusion after an initially successful thrombolysis treatment can occur and is associated with increased morbidity and mortality. The authors present the successful use of abciximab, a platelet glycoprotein IIb/IIIa receptor inhibitor, in a patient with a thrombotic occlusion of the proximal middle cerebral artery, which was refractory to combined IV and intra-arterial thrombolysis and percutaneous intracranial balloon angioplasty.

Abciximab↗

Topography and instability of monolayers near domain boundaries.

We theoretically study the topography of a biphasic surfactant monolayer in the vicinity of domain boundaries. The differing elastic properties of the two phases generally lead to a nonflat topography of "mesas," where domains of one phase are elevated with respect to the other phase. The mesas are steep but low, having heights of up to 10 nm. As the monolayer is laterally compressed, the mesas develop overhangs and eventually become unstable at a surface tension of about K(deltac(0))(2) (deltac(0) being the difference in spontaneous curvature and K a bending modulus). In addition, the boundary is found to undergo a topography-induced rippling instability upon compression, if its line tension is smaller than about Kdeltac(0). The effect of diffuse boundaries on these features and the topographic behavior near a critical point are also examined. We discuss the relevance of our findings to several experimental observations related to surfactant monolayers: (i) small topographic features recently found near domain boundaries; (ii) folding behavior observed in mixed phospholipid monolayers and model lung surfactants; (iii) roughening of domain boundaries seen under lateral compression; (iv) the absence of biphasic structures in tensionless surfactant films.

Journal Article↗

Inhibition of cytokine-induced vascular cell adhesion molecule-1 expression; possible mechanism for anti-atherogenic effect of Agastache rugosa.

Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) play an important role during the early stages of atherogenesis. Agastache rugosa has an anti-atherogenic effect in low density lipoprotein receptor -/- mice. Moreover, A. rugosa reduced macrophage infiltration and VCAM-1 expression has been localized in aortic endothelium that overlies early foam cell lesions. This study ascertained that tilianin (100 microM), a major component of A. rugosa, inhibits the tumor necrotic factor-alpha (TNF-alpha)-induced expression of VCAM-1 by 74% in cultured human umbilical vein endothelial cells (HUVECs). Also, tilianin (100 microM) reduced TNF-alpha-induced activation of nuclear factor-kappaB in HUVECs.

Animals↗

IFNalpha sensitizes ME-180 human cervical cancer cells to TNFalpha-induced apoptosis by inhibiting cytoprotective NF-kappaB activation.

Tumor necrosis factor alpha (TNFalpha) induces apoptosis of a variety of tumor cell types. The anti-tumor effect of TNFalpha is often augmented by interferon (IFN) gamma. We hypothesized that IFNalpha, which shares many biological activities with IFNgamma, might also synergize with TNFalpha for the induction of tumor cell death. We tested our hypothesis using ME-180 human cervical cancer cells exposed to either IFNalpha or TNFalpha alone or both. We analyzed the death of ME-180 cells by biochemical and cytological means, and investigated the molecular mechanism underlying cytotoxic synergism between the two cytokines. We found that (i) IFNalpha/TNFalpha synergistically induced apoptosis of ME-180 cells, which was accompanied by activation of caspases-3 and -8; (ii) IFNalpha induced signal transducer and activator of transcription (STAT) 1 phosphorylation, and transfection of phosphorylation-defective STAT1 dominant-negative mutant inhibited IFNalpha/TNFalpha-induced apoptosis; (iii) inhibition of nuclear factor kappaB (NF-kappaB) by proteasome inhibitor MG-132 sensitized ME-180 cells to TNFalpha alone; (iv) IFNalpha treatment attenuated TNFalpha-induced NF-kappaB reporter activity, while it did not inhibit DNA binding of NF-kappaB. Taken collectively, our results indicate that IFNalpha sensitizes ME-180 cells to TNFalpha-induced apoptosis by inhibiting TNFalpha-mediated cytoprotective NF-kappaB activation, and this sensitizing effect of IFNalpha is mediated through a STAT1-dependent pathway.

Apoptosis↗

Successful interferon alpha therapy in atopic dermatitis of Besnier's prurigo pattern with normal serum IgE and blood eosinophil fraction: randomized case-controlled study.

A randomized case-controlled study was carried out to investigate for interferon alpha therapy in atopic dermatitis (AD) of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. Interferon alpha therapy was conducted on 14 non-responders to interferon gamma and subsequent thymopentin therapy among 100 atopic dermatitis patients. Eight patients who improved significantly, showed skin lesions of the Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. For the randomized prospective case-controlled study, 44 patients with the above characteristics were selected. Thirteen Besnier's prurigo patients were treated with interferon alpha therapy, ten with interferon gamma, ten with thymopentin, and the remaining 11 were untreated as the control group. With interferon alpha therapy, 11 out of 13 Besnier's prurigo patients with normal IgE and normal blood eosinophil fraction improved significantly, two out of ten improved with interferon gamma therapy, and none improved with thymopentin therapy or in the untreated control group. Interferon alpha therapy was effective on AD of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. These results suggest the possibility of non-IgE-mediated AD and the heterogeneity of atopic dermatitis.

Adjuvants, Immunologic↗

Time- and depth-dependent changes in crosslinking and oxidation of shelf-aged polyethylene acetabular liners.

Since crosslinking and oxidation of ultrahigh-molecular-weight polyethylene (UHMWPE) have important roles in determining the wear resistance of UHMWPE total joint components, the time and depth dependence of crosslinking and oxidation of new shelf-aged (2-11 years), ready-to-implant acetabular liners were studied by using solvent extraction and Fourier transform infrared spectroscopy. The ultrastructure of these materials also was examined by using low-voltage scanning electron microscopy in an oil-free vacuum. Oxidation levels increased with time and with depth (p < 0.0001) from the surface of the older liners to a maximum value at about 1-2 mm below the surface, then decreased. They were minimal at the midsection of the liners. The crosslinking of these liners decreased with time and depth (p < 0.0001) and was inversely proportional to the level of oxidation. High and depth-dependent oxidation levels were observed in all older liners made from GUR 415 and 412 resins but were distinctly absent from a comparably aged (i.e., 9 years) liner made from 1900 CM-resin. Some liners showed varying degrees of inhomogeneous and discontinuous morphologic ultrastructure in addition to varying amounts of porosity while others had a more homogeneous ultrastructure. Oxidation and crosslinking of polyethylene are time- and depth-dependent processes that are mutually competitive. We suggest that resin choice and perhaps consolidation-related variables lead to differences in polyethylene's ultrastructure. These ultrastructural differences in polyethylene's inhomogeneities, that is, the type (interconnected or closed-cell) or extent may affect the oxidation resistance of polyethylene. While oxygen diffusion to free radicals in polyethylene already is known to explain some of these time- and depth-dependent effects, perhaps such ultrastructural variations also may facilitate or retard oxygen diffusion in this material. Resin-based ultrastructural variability partially may explain the variability in the clinical performance of polyethylene total joint implant components. Thus resin choice or processing modifications related to polyethylene's ultrastructure may increase its oxidation resistance and ultimately improve the clinical wear performance of polyethylene total joint orthopedic implants.

Acetabulum↗

Degradable and injectable poly(aldehyde guluronate) hydrogels for bone tissue engineering.

Degradable and injectable hydrogels may be ideal for bone-tissue engineering, especially in the craniofacial region because of the ease of access for injection. Alginate hydrogels potentially could be used as injectable cell delivery vehicles, but they exhibit a limited range of mechanical properties and uncontrollable disintegration time. Therefore we synthesized new hydrogels, composed of poly(aldehyde guluronate) (PAG) and adipic acid dihydrazide, that have a wide range of mechanical stiffness and controllable degradation rate. MC3T3-E1 cells adhered and multiplied on PAG hydrogels in vitro. When primary rat calvarial osteoblasts were mixed with PAG hydrogels and subcutaneously injected into the backs of mice, mineralized bone tissues were formed 9 weeks following implantation. These hydrogels may find wide utility as an injectable delivery system for bone precursor cells as well as for other applications in tissue engineering.

3T3 Cells↗

Hematein inhibits tumor necrotic factor-alpha-induced vascular cell adhesion molecule-1 and NF-kappaB-dependent gene expression in human vascular endothelial cells.

Monocyte adhesion to the endothelium via adhesion molecules is one of the earliest events in atherogenesis. It has been suggested that vascular cell adhesion molecule-1 (VCAM-1) plays a very important role in the recruitment of monocytes in atherosclerosis. The aim of our study was to evaluate whether hematein can influence the expression of VCAM-1 and the transcription of nuclear factor-kappaB (NF-kappaB)-dependent genes. Immunohistochemistry revealed that mouse aortic artery endothelial cells express VCAM-1 after feeding a high cholesterol diet for 8 weeks. Hematein dose dependently suppressed TNF-alpha-induced VCAM-1 in both surface (30.8%) and soluble protein (65%) production in HUVECs. The transcription level of VCAM-1 was measured by Northern blot analysis, and decreased VCAM-1 protein expression was associated with a reduction of VCAM-1 mRNA expression. Transient transfection study of NF-kappaB promoter construct and electrophoretic mobility shift assay suggested that hematein inhibited both NF-kappaB-dependent gene expression and NF-kappaB activation induced by TNF-alpha. Our results suggest that the down-regulation of VCAM-1 expression by hematein may in part be due to the inhibition of NF-kappaB-dependent gene expression.

Animals↗

Tyrosine phosphorylation translocates beta-catenin from cell-->cell interface to the cytoplasm, but does not significantly enhance the LEF-1-dependent transactivating function.

beta-catenin plays an essential role in cells, not only as a cadherin-associated complex, but also as a signaling molecule in the nucleus. Tyrosine phosphorylation of beta-catenin has been shown to correlate with tumorigenesis, cell migration, and developmental processes. However, its exact effects on downstream targets in the nucleus are not yet clear. In this study, we used HCT-15 colon carcinoma and NIH 3T3 fibroblasts as models to investigate the effects of a phosphotyrosine phosphatase (PTPase) inhibitor on the localization of beta-catenin, the binding affinity to LEF-1 (Lymphoid Enhancer Factor), and on LEF-1-dependent transactivation function. Treatment with a PTPase inhibitor, pervanadate, increased the tyrosine phosphorylation of beta-catenin in a time-dependent manner and led to its relocation from cell-cell interfaces to the cytoplasm. This phosphorylation/dephosphorylation of beta-catenin does not require its presence at cell-cell interfaces. However, tyrosine phosphorylation of beta-catenin does not change its binding affinity to LEF-1 nor enhance cyclin D1 transactivation, a nuclear target of beta-catenin/LEF-1. This result suggests that tyrosine phosphorylation of beta-catenin has effects on the binding to cadherins in the cytoplasm but not on its LEF-1-dependent transactivating function in the nucleus.

3T3 Cells↗

Direct and precise determination of environmental radionuclides in solid materials using a modified Marinelli beaker and a HPGe detector.

A simple but precise detection method was studied for the determination of natural radionuclides using a conventional HPGe detector. A new aluminium beaker instead of a plastic Marinelli beaker was constructed and examined to reach radioactive equilibrium conditions between radon and its daughter elements without the escape of gaseous radon. Using this beaker fifteen natural radionuclides from three natural decay series could be determined by direct gamma-ray measurement and sixteen radionuclides could be determined indirectly after radioactive equilibrium had been reached. Analytical results from ground water were compared with those from conventional alpha spectroscopy and the results agreed well within 12% difference. Nitrogen gas purge was used to replace the surrounding air of the detector to obtain a stable background and reducing the interference of radon daughter nuclides in the atmosphere. The use of nitrogen purging and the aluminium Marinelli beaker results in an approximately tenfold increase of sensitivity and a decrease of the detection limit of 226Ra to about 0.74 Bq kg(-1) in soil samples.

Journal Article↗

Impact of splenectomy for lymph node dissection on long-term surgical outcome in gastric cancer.

BACKGROUND: In the treatment of gastric cancer, splenectomy is performed for effective lymph node dissection around the splenic artery and splenic hilum. The purpose of this study was to clarify the long-term outcome of splenectomy in the treatment of gastric cancer. METHODS: The effect of splenectomy on recurrence and prognosis was examined in a retrospective analysis of 665 patients who had undergone curative total gastrectomy for gastric carcinoma from 1987 to 1996. The risk factors associated with recurrence and prognosis were investigated by univariate and multivariate analysis. RESULTS: The splenectomy group showed more advanced lesions and a higher recurrence rate than the spleen-preserved group. However, after adjusting for the TNM (tumor, node, metastasis) stage, there was no significant difference in recurrence rate and pattern between the two groups. Logistic regression analysis revealed that gross type, serosal invasion, and nodal metastasis were independent risk factors for recurrence while splenectomy was not. When comparing patients with the same TNM (tumor, node, metastasis) stages, no significant difference in the 5-year survival rates was apparent. Multivariate analysis demonstrated that age, serosal invasion, and nodal metastasis were independent prognostic factors whereas splenectomy was not. CONCLUSIONS: These data suggest that splenectomy for lymph node dissection in gastric cancer is not effective regarding long-term patient prognosis.

Adenocarcinoma↗

p53, BCL-2, and Ki-67 expression according to tumor response after concurrent chemoradiotherapy for advanced rectal cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer is an important modality for curative resection, but tumors show wide spectrum response. The purpose of this study was to investigate any correlation among related genetic mutations, proliferative index, and tumor response after CCRT. METHODS: This study included 23 patients with rectal cancer, who were preoperatively staged as at least T3 N1 or T4 (determined by transrectal ultrasonography and MRI). Enrolled patients were given 5-FU 450 mg/m2/day and leucovorin 20 mg/m2/day intravenously for 5 days during weeks 1 and 5 of radiotherapy (45-54 Gy). Surgical resection was performed 4 weeks after completion of the scheduled treatment. Tumor response was classified as CR (complete response), PR (partial response: 50% diminution of tumor volume and downstaging), and NR (no response). Paraffin-embedded tissue obtained before chemoradiotherapy was studied by immunohistochemical staining for p53, BCL-2, and Ki-67. The extent of tumor response was correlated with proliferative activity and was measured by immunostaining Ki-67 proliferative antigen and the expression of p53 and BCL-2 oncoproteins. RESULTS: All patients were resectable. CR was obtained in 4 patients, PR in 10 patients, and NR in 9 patients. The p53 mutation was noted in 16 patients: NR in 5 patients, PR in 9 patients, and CR in 2 patients (P = .638). BCL-2 expression was noted in 11 patients: NR in 4 patients, PR in 3 patients, and CR in 4 patients (P = .799). The Ki-67 labeling index was NR: 615.4+/-47.2; PR: 663.2+/-20.4; and CR: 765.5+/-58.3 (CR + PR vs. NR, P = .029). CONCLUSIONS: Immunohistochemical expression of p53 and BCL-2 does not correlate with tumor response after CCRT, but Ki-67 labeling may be a useful parameter for radiosensitive tumors selected for CCRT.

Adenocarcinoma↗