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Biomedical subjects

Y S Choi

Publications and source records attributed to Y S Choi.

At least 37 records · Page 2Linked to original sources

Study on gelatin-containing artificial skin IV: A comparative study on the effect of antibiotic and EGF on cell proliferation during epidermal healing.

Gelatin-hyaluronate sponge with and without antibiotic and epidermal growth factor (EGF) were prepared and compared. Four types of sponges were applied on the full-thickness dorsal skin defect of Wistar rat. The effects of antibiotic and EGF in gelatin-hyaluronate sponge on wound healing were investigated by light microscopy and image analyzer at postoperative days of 5, 12 and 21. An immunohistochemical technique, employing PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA) was applied to wounded tissue sections. The number of PC10-positive cells was very high for the sponge with EGF at postoperative day 5, then gradually decreased with time. Also we found that antibiotics restrained the cell proliferation during the migratory phase. The sponge with both antibiotic and EGF showed good wound healing performances on the whole for a healing period. The epithelium was regenerated fast with EGF-impregnated sponges at day 5, but each sample had nearly the same length of regenerated epithelium at day 12.

Animals↗

Mitochondrial transcription factor A (mtTFA) and diabetes.

Mitochondrial DNA (mtDNA) content decreased in an age-dependent manner and may be one of the causal factors in age-related type 2 diabetes. Mitochondrial transcription factor A (mtTFA), which provides the replication primer, plays a key role for the regulation of mtDNA replication and its level is proportional to mtDNA. Here, we studied on the regulatory mechanism of mtTFA expression and the factors affecting the transcriptional activity of the mtTFA promoter. The promoter of human mtTFA contains 67 CpG dinucleotides. When the plasmids bearing the mtTFA promoter (2378 bp) linked to luciferase were transiently transfected into HepG2 cells, in vitro methylation of NRF-1 site by HhaI methylase abolished the mtTFA promoter activity up to 90%, implying that the CpG methylation of NRF-1 site inactivate mtTFA promoter-driven transcriptional activity. Besides the promoter methylation, the exogenous hydrogen peroxide or glucose also modulates the promoter activity of mtTFA. The bacterially overexpressed mtTFA protein exhibits a strong binding affinity to circular DNA (perhaps to mtDNA in mitochondria in vivo) and the protection of the DNA from cleavage by a hydrogen peroxide attack. Taken all these results together, age-related alterations of oxidative stress may affect mtDNA replication via regulating mtTFA activity. Furthermore, a vicious cycle may be present between mtTFA protein level and oxidative stress in the sense of DNA damage. Further studies were necessary to prove the presence of methyl cytosine in the mtTFA promoter of either an aged or a diabetic person and the effect of oxidative stress on the mtTFA function and expression resulting in a change of the mtDNA copy number.

Amino Acid Sequence↗

Torsion angle based design of peptidomimetics: a dipeptidic template adopting beta-I turn (Ac-Aib-AzGly--NH(2)).

We have attempted to design a model dipeptide (acetyl dipeptide amide, Ac-CA1-CA2--NH(2)) that can adopt specifically typical torsion angles of the beta-I turn (phi(i+1), psi(i+1), phi(i+2), psi(i+2)=-60 degrees, -30 degrees, -90 degrees, 0 degrees ). The key of the design is the combination of constrained amino acids that prefer to adopt the desired torsion angles. We chose Aib (aminoisobutyric acid) as the first residue of which phi and psi angles must be -60 degrees and -30 degrees, respectively. Then, we selected an azaamino acid as the second residue since previous studies have indicated that they prefer to adopt +/-90 degrees of phi angle and 0 degrees or 180 degrees of psi angle. The conformational preference of the resulting Ac-Aib-AzGly--NH(2) is investigated using ab initio methods. The conformations implying beta-I and beta-I' turns are energetically most favorable, as we expected. Thus, we synthesized the designed molecule on the solid phase considering the future generation of combinatorial libraries using an automatic peptide synthesizer. Then, NMR spectroscopy was carried out to confirm their conformational preference in solution was carried out. The results indicated that the Ac-Aib-AzGly--NH(2) adopt beta-I or beta-I' turns in solution forming an intramolecular hydrogen bonding between Ac--C(O) and terminal NH(2). We believe that such a small peptidomimetic template is highly useful for the design of drug candidates and molecular devices.

Dipeptides↗

Studies on gelatin-based sponges. Part III: a comparative study of cross-linked gelatin/alginate, gelatin/hyaluronate and chitosan/hyaluronate sponges and their application as a wound dressing in full-thickness skin defect of rat.

Novel cross-linked sponges composed of gelatin/alginate and gelatin/hyaluronate and chitosan/hyaluronate (GH, GA and CH, respectively) were prepared and compared. Six different sponges with or without silver sulfadiazine (AgSD) were applied on the full-thickness dorsal skin defect of Wistar rat. The histology and epidermal wound healing rates of the skin defects were investigated by light microscopy and computerized morphometry 5 and 12 days post-operatively. In our full-thickness wound model (diameter 1 cm), the AgSD-impregnated sponges showed good wound healing performances on the whole. However, there appeared meaningful differences of wound healing between the gelatin-based sponges (GH, GA) and the CH. GH with AgSD was found to show the best wound healing properties as a wound dressing resulting from histological findings and computerized morphometric analysis of epidermal healing.

Journal Article↗

Establishment of a follicular lymphoma cell line (FLK-1) dependent on follicular dendritic cell-like cell line HK.

A novel cell line, FLK-1, was established from bone marrow cells of a patient with follicular lymphoma by means of co-culture with follicular dendritic cell (FDC)-like cell line HK. Immunophenotypic analysis showed that FLK-1 expressed CD10, CD19, CD20, CD38, IgG and HLA-DR, which is a typical feature of germinal center B cells. Cytogenetic analysis of FLK-1 demonstrated t(14;18)(q32;q21) translocation involving BCL2 and immunoglobulin heavy chain genes. Especially noteworthy is that the growth of FLK-1 was found to be dependent on a FDC line, HK. When HK cells were removed from the culture, FLK-1 cells stopped growing and eventually died. An apoptotic mechanism appeared to be involved as indicated by the presence of chromosome condensation and DNA ladder formation. The culture experiment using micropore membranes showed that soluble factor(s) of HK cells supported the growth, while direct cell-to-cell contact appeared to be necessary for longterm cell proliferation. These findings suggest the importance of the micro-environment for follicular lymphoma cells to grow. The FLK-1 cell line may thus prove to be useful for studying the growth mechanism of follicular lymphoma and provide new insights into the pathogenesis of follicular lymphoma.

Cell Communication↗

Vitamin C prevents radiation-induced endothelium-dependent vasomotor dysfunction and de-endothelialization by inhibiting oxidative damage in the rat.

1. The present study was undertaken to determine whether endothelial function or morphology was altered in aortic rings of rats after irradiation, to investigate the mechanism of radiation effects on the endothelium and to examine the effect of vitamin C treatment against radiation-induced damage of the endothelium. 2. Female Sprague-Dawley rats were randomized into four groups (control, radiation, radiation + vitamin C, radiation + vitamin C + NG-nitro-L-arginine methyl ester (L-NAME); n = 10 for each group and n = 7 for the control group) and were irradiated with 10 Gy of 137Cs as a radiation source. Segments of the thoracic aorta were obtained and isometric tension, levels of 8-hydroxydeoxyguanosine (OH-dG) and immunohistochemical staining were measured. 3. Irradiation significantly impaired the acetylcholine-induced vasodilation of aortic segments, an effect that could be prevented by pretreatment with vitamin C (500 mg/kg per day). This beneficial effect of vitamin C was abolished by the addition of L-NAME (100 microg/kg per day), an inhibitor of nitric oxide (NO) synthesis. Irradiation significantly increased the level of OH-dG in the aorta (1.02 +/- 0.27 vs 2.61 +/- 0.78 OH-dG/105 deoxyguanosine (dG) for control and irradiated tissues, respectively; P < 0.01), an increase that was prevented by vitamin C treatment (1.59 +/- 0.23 OH-dG/105 dG; P < 0.01). Irradiation caused significant de-endothelialization (von Willebrand factor (vWF) staining was 93 +/- 7 vs 100% in irradiated and control tissues, respectively; P < 0.05) and this was prevented by vitamin C treatment (vWF staining 98 +/- 3%; P < 0.05). 4. Radiation caused endothelial damage and impaired NO production through oxidative injury, resulting in a selective impairment of endothelial-dependent vasodilation that could be prevented by vitamin C, partly through anti-oxidant mechanisms.

Acetylcholine↗

The value of contrast echocardiography in the diagnosis of patent ductus arteriosus with Eisenmenger's syndrome.

When patent ductus arteriosus (PDA) is complicated by pulmonary hypertension resulting in a right-to-left shunt, an erroneous diagnosis of primary pulmonary hypertension may be made, even after echocardiographic examination. Among the 8 patients referred to our echocardiography laboratory with the diagnosis of primary pulmonary hypertension between June 1994 and November 1999, 2 patients were found to have PDA with Eisenmenger's syndrome. Patent ductus arteriosus with Eisenmenger's syndrome can be diagnosed by the opacification of the abdominal aorta without opacification of the left-sided chambers during contrast echocardiography.

Adolescent↗

Immobilization of arsenic in tailing by using iron and hydrogen peroxide.

Under environmental conditions, arsenic (As) reveals anionic behavior and is converted into various forms in accordance with the Eh/pH condition. This causes the difficulty of treating As with other heavy metals in tailing. This study was carried out to develop the immobilization method of arsenic in tailing as ferric arsenate (FeAsO4) using hydrogen peroxide. According to experimental results, the extracted concentrations of arsenic and iron (Fe) from tailing were reduced up to 84% and 93%, respectively. In the experiment using pure Pyrite (FeS2) and As solution, As concentration decreased with an increase of hydrogen peroxide dosage. The experimental results of re-extraction showed that only 10% of As and 20% of Fe were extracted in the case of using hydrogen peroxide. As a result, the long-term stability of this method was clarified.

Arsenic↗

Functional effects of TNF and lymphotoxin alpha1beta2 on FDC-like cells.

Recent studies suggest that tumor necrosis factor (TNF) family members such as TNFalpha and lymphotoxin alphabeta (LTalpha1beta2) are important in the development of follicular dendritic cells (FDCs) and maintenance of FDC function. In this study we used FDC-like cells (FDC-LC) cultured from normal human tonsil and investigated the effects of TNF and LTalpha1beta2 on expression of adhesion molecules and the production of cytokines and chemokines. TNF and LTalpha1beta2 both increased the expression of VCAM-1 and ICAM-1 on FDC-LC. In addition, IL-4 with LTalpha1beta2 synergistically increased the expression of VCAM-1, but not ICAM-1. Cytokine IL-6 and IL-15 mRNAs were induced following stimulation with TNF and LTalpha1beta2. These two cytokines were present in FDC-LC supernatants by ELISA and increased following TNF and LTalpha1beta2 stimulation. We also examined FDC-LC for chemokines, which affect B cells, including IL-8, SDF-1, MIP3beta/ELC, and BCA-1/BLC. SDF-1 mRNA and protein were expressed by FDC-LC, and following stimulation with TNF and LTalpha1beta2, decreases in both were observed. Therefore, TNF and LTalpha1beta2, which are produced by activated B cells, increased the expression of adhesion molecules and cytokines from FDC-LC, potentially providing key signals to support germinal center B cell survival and differentiation.

Cell Line↗

Identification of a human follicular dendritic cell molecule that stimulates germinal center B cell growth.

The initial interaction between B cells and follicular dendritic cells (FDCs) appears to be essential for germinal center (GC) formation. To identify molecules regulating this interaction, we generated FDC-staining monoclonal antibodies (mAbs) and screened them for their ability to block FDC-mediated costimulation of growth and differentiation of CD40-stimulated B cells. Using one of the inhibitory mAbs, 8D6, we expression cloned the cDNA encoding the 8D6 antigen (Ag) from a human FDC line, HK. The 8D6 Ag is a novel protein of 282 amino acids that is expressed abundantly on FDCs. Monolayers of COS cells transiently transfected with the 8D6 Ag cDNA stimulate B cell growth. The mAb 8D6 blocks the costimulatory function completely. The inhibitory activity of the mAb 8D6 was demonstrated to be due to an inhibition of cell cycle progression of CD40 ligand-stimulated GC B cells. In addition, the mAb 8D6 inhibits the growth of a lymphoma of GC origin, L3055, which depends on FDCs or HK cells for its growth. These findings suggest that the primary function of FDCs in the GC is to stimulate B cell growth. An FDC signal molecule, 8D6 Ag, may be an important molecule to mediate this function.

Animals↗

Synergistic effect of angiotensin-converting enzyme and angiotensinogen gene on cardiac hypertrophy.

AIMS: There are controversies concerning the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH), and the unclear association between angiotensinogen (ATG) M235T polymorphism and LVH. We investigated both the separate and interactive effects of these two genes on LVH in patients (N=396) with cardiovascular disease and normal healthy volunteers (N=133). RESULTS: Frequency of DD genotype of ACE gene was significantly (P<0.05) higher in patients with LVH than patients without LVH or normal controls. Frequency of IT genotype of ATG gene in patients with LVH was significantly (P<0.01) greater than that in normal controls or marginally (P=0.1) higher than that in patients without LVH. These findings were also observed in normotensive patients and normal controls after excluding hypertensive patients. Only in patient group, the frequency of DD genotype in the highest quartile of LVMI was significantly greater than that in the lowest quartile (P<0.05). The higher tendency of TT genotype in the highest quartile patients compared with that in the lowest, did not reach statistical significance. In combined genotype analysis, there was a remarkable difference in LVMI between the two extreme double homozygotes only in patient group (156+/-25 versus 109+/-25 g/m2 for TT+DD versus MM+II) (P<0.01). In ANCOVA, the interaction term composed of ACE and ATG genotype was a significant independent variable for LVMI only in the male patient group (P<0.01). CONCLUSION: The D-allele of ACE and T-allele of ATG gene exert a synergistic effect on cardiac hypertrophy in male patients with cardiovascular diseases, but not in normal healthy population.

Adult↗

Distinct role of follicular dendritic cells and T cells in the proliferation, differentiation, and apoptosis of a centroblast cell line, L3055.

Germinal center (GC) B cells undergo complex interactions with follicular dendritic cells (FDC) and T cells in the course of differentiation into memory B and plasma cells. To delineate the individual roles of FDC and T cells at each stage of GC B cell differentiation at the clonal level and to analyze the signals involved, we adopted a unique experimental model using an FDC line, HK, and a lymphoma cell line, L3055, that resembles centroblasts. A detailed phenotypic analysis revealed L3055 cells to be a clonal population originating from the GC. Like freshly isolated centroblasts, L3055 cells underwent spontaneous apoptosis when cultured in the absence of fresh FDC or HK cells. L3055 cells proliferated continuously in the presence of HK cells, while they differentiated into a population with the phenotype of centrocytes after stimulation with CD40 ligand (CD40L) and IL-4. The CD40L-stimulated L3055 cells underwent CD95-mediated apoptosis, which was reminiscent of the feature of CD40L-stimulated tonsillar GC B cells. In contrast to HK cells that did not protect L3055 cells from anti-Ig killing, CD40L plus IL-2, IL-4, and IL-10 prevented anti-Ig-induced apoptosis. These experimental results demonstrate a distinct function of FDC and activated T cells, in that FDC provide signals for rapid proliferation of centroblasts, whereas T cells confer signals for differentiation of centroblasts into centrocytes and resistance to B cell receptor-mediated apoptosis. T cells collaborate with FDC in the protection and expansion of the Ag-specific GC B cells.

Adolescent↗

Upregulation of phospholipase D in astrocytes in response to transient forebrain ischemia.

Previous in vitro studies using cell cultures or brain slices have demonstrated that phospholipase D (PLD) in the nervous system is involved in the signaling mechanism in response to a variety of agonists. However, little is known about the pathophysiological role of PLD-mediated signaling in the adult brain. We examined the changes in the expression of a PLD isozyme, PLD1, in the adult rat hippocampus, using immunological approaches and an assay for PLD activity after transient forebrain ischemia (four-vessel occlusion model) that results in the selective delayed death of CA1 pyramidal cells and induces reactive astrocytes in the CA1 subfield. In the control hippocampus, PLD1 the level of immunoreactivity was very low. After ischemia, in parallel with the results of Western blot analysis and the PLD activity assay, immunohistochemical analysis of PLD1 demonstrated that the immunoreactive proteins peaked at 7-14 days and were most prominent in the CA1 and the dentate hilar region. The temporal and spatial patterns of immunoreactivity of both PLD1 and glial fibrillary acidic protein (GFAP) were very similar, indicating that reactive astrocytes express PLD1, confirmed by double staining for PLD1 and GFAP. These results demonstrate that reactive astrocytes upregulate PLD in vivo after injury in the adult rat hippocampus.

Animals↗

Regulation of CD27 expression in the course of germinal center B cell differentiation: the pivotal role of IL-10.

The molecules of the TNF superfamily and their receptors play crucial roles in the humoral immune response. In view of the powerful effects on germinal center (GC) B cell differentiation, the expression of these molecules should be tightly regulated. In this study, we have undertaken a detailed analysis of the regulation of CD27 expression following the differentiation of GC B cells supported by a follicular dendritic cell line. We show that CD27 is differentially expressed on B cell subpopulations at different stages of differentiation. Naive B cells are virtually negative but plasma cells generated in vivo are strongly positive for CD27 expression. GC B cells that exhibit a moderate expression of CD27 remarkably up-regulate the expression levels of this molecule when they differentiate into plasma cells, which is induced by IL-10. The up-regulation of CD27 expression correlates with that of CD38. Therefore, high expression of CD27 molecules emerges as a specific marker for plasma cells. Our results suggest an important role for CD27 in the differentiation of GC B cells into plasma cells. Evaluation of CD27 expression levels may be of a clinical significance in assessment of B cell maturation in immunocompromised patients.

Animals↗

Relationship between the extent of fracture and the degree of enophthalmos in isolated blowout fractures of the medial orbital wall.

PURPOSE: This study investigated the relationship between the extent of fracture and enophthalmos in blowout fractures of the medial orbital wall. PATIENTS AND METHODS: Nine patients with isolated blowout fractures of the medial orbital wall, confirmed by computed tomography scans, were evaluated. The area of fracture and the volume of herniated orbital tissue were determined from computed tomography scans using simple linear measurements. Each of the calculated values for area and volume were compared with the degree of enophthalmos to determine whether there was any significant relationship between them. RESULTS: Enophthalmos increased proportionally as the area of fracture or the volume of herniated orbital tissue increased (P < .05). The area of fracture and the volume of herniated orbital tissue associated with 2 mm of enophthalmos were 1.9 cm2 and 0.9 mL, respectively, as calculated from the regression curve. CONCLUSION: Enophthalmos of 2 mm or more, which is a frequent indication for surgery, can be expected when the area of fracture is 1.9 cm2 or more, or the volume of herniated orbital tissue is 0.9 mL or more.

Adult↗

Role of azaamino acid residue in beta-turn formation and stability in designed peptide.

The structural perturbation induced by C(alpha)-->N(alpha) exchange in azaamino acid-containing peptides was predicted by ab initio calculation of the 6-31G* and 3-21G* levels. The global energy-minimum conformations for model compounds, For-azaXaa-NH2 (Xaa=Gly, Ala, Leu) appeared to be the beta-turn motif with a dihedral angle of phi= +/- 90 degrees, psi=0 degrees. This suggests that incorporation of the azaXaa residue into the i+2 position of designed peptides could stabilize the beta-turn structure. The model azaLeu-containing peptide, Boc-Phe-azaLeu-Ala-OMe, which is predicted to adopt a beta-turn conformation was designed and synthesized in order to experimentally elucidate the role of the azaamino acid residue. Its structural preference in organic solvents was investigated using 1H NMR, molecular modelling and IR spectroscopy. The temperature coefficients of amide protons, the characteristic NOE patterns, the restrained molecular dynamics simulation and IR spectroscopy defined the dihedral angles [ (phi i+1, psi i+1) (phi i+2, psi i+2)] of the Phe-azaLeu fragment in the model peptide, Boc-Phe-azaLeu-Ala-OMe, as [(-59 degrees, 127 degrees) (107 degrees, -4 degrees)]. This solution conformation supports a betaII-turn structural preference in azaLeu-containing peptides as predicted by the quantum chemical calculation. Therefore, intercalation of the azaamino acid residue into the i+2 position in synthetic peptides is expected to provide a stable beta-turn formation, and this could be utilized in the design of new peptidomimetics adopting a beta-turn scaffold.

Aza Compounds↗

Endonasal endoscopic reduction of blowout fractures of the medial orbital wall.

PURPOSE: This article describes the endonasal endoscopic reduction (EER) of blowout fractures (BOFs) of the medial orbital walls and reports the clinical results. PATIENTS AND METHODS: Sixteen patients who underwent EER for a BOF of the medial orbital wall were analyzed. The surgical indications for treatment were diplopia, limitation of eye movements, and significant enophthalmos. They were followed-up for at least 3 months after the surgery. Surgical techniques, surgical results, and postoperative complications were reviewed. RESULTS: There were no significant intraoperative or postoperative complications. Fourteen patients showed complete resolution of symptoms after the surgery. One patient, who had persistent diplopia and remaining enophthalmos, underwent medial wall reconstruction with a Medpor surgical implant (Porex Surgical Inc, College Park, GA) by a transorbital approach. Another patient, who had residual enophthalmos, had correction of enophthalmos after insertion of a Medpor implant. Both patients are now symptom-free. CONCLUSION: The results indicate that EER is a safe and effective technique for the treatment of BOFs of the medial orbital wall.

Adolescent↗

Differentiation between reversible and irreversible restrictive left ventricular filling patterns with the use of mitral annulus velocity.

A restrictive left ventricular filling pattern is generally recognized as an ominous prognostic sign in patients with congestive heart failure. Recently, this filling pattern has been further categorized into reversible and irreversible groups according to the changes in the mitral inflow pattern after preload reduction; furthermore, the prognosis is reported to be different for the two groups. Forty-two patients with a restrictive left ventricular filling pattern who could adequately perform Valsalva's maneuver were studied. Baseline peak early (E) and late (A) mitral inflow velocities, E/A ratio, deceleration time of E velocity, peak early (E') and late (A') diastolic mitral annulus velocities, and E'/A' ratio were obtained. During Valsalva's maneuver, the E/A ratio reversed (<1) in fifteen patients (15/42, 36%). These patients were categorized as belonging to the reversible group. Among the baseline mitral inflow and mitral annulus velocity parameters, A' > 0.05 m/s best discriminated between the reversible and irreversible restrictive left ventricular filling patterns, with a sensitivity of 80% and a specificity of 85%.

Adult↗