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Biomedical subjects

Y K Kim

Publications and source records attributed to Y K Kim.

At least 37 records · Page 2Linked to original sources

Effects of peripheral benzodiazepine receptor ligands on proliferation and differentiation of human mesenchymal stem cells.

The peripheral benzodiazepine receptor (PBR) has been known to have many functions such as a role in cell proliferation, cell differentiation, steroidogenesis, calcium flow, cellular respiration, cellular immunity, malignancy, and apoptosis. However, the presence of PBR has not been examined in mesenchymal stem cells. In this study, we demonstrated the expression of PBR in human bone marrow stromal cells (hBMSCs) and human adipose stromal cells (hATSCs) by RT-PCR and immunocytochemistry. To determine the roles of PBR in cellular functions of human mesenchymal stem cells (hMSCs), effects of diazepam, PK11195, and Ro5-4864 were examined. Adipose differentiation of hMSCs was decreased by high concentration of PBR ligands (50 microM), whereas it was increased by low concentrations of PBR ligands (<10 microM). PBR ligands showed a biphasic effect on glycerol-3-phosphate dehydrogenase (GPDH) activity. High concentration of PBR ligands (from 25 to 75 microM) inhibited proliferation of hMSCs. However, clonazepam, which does not have an affinity to PBR, did not affect adipose differentiation and proliferation of hMSCs. The PBR ligands did not induce cell death in hMSCs. PK11195 (50 microM) and Ro5-5864 (50 microM) induced cell cycle arrest in the G(2)/M phase. These results indicate that PBR ligands play roles in adipose differentiation and proliferation of hMSCs.

Anti-Anxiety Agents↗

Phylogenetic analysis of protozoa in the rumen contents of cow based on the 18S rDNA sequences.

AIMS: To examine the diversity of protozoa in the rumen contents of cow. METHODS AND RESULTS: Protozoa that inhabit the rumen were detected by PCR using protozoan-specific primers. Libraries of protozoan rDNA sequences were constructed from rumen fluid, solid tissues and epithelium. Twenty-three clones isolated from rumen fluid fell into two genera identified as Entodinium (69.6% of clones) and Epidinium (31.4% of clones). Of the clones isolated from rumen fluid, a moderate number were unidentifiable (30.4%). CONCLUSIONS: The predominant protozoan genus identified in the whole rumen belonged to the Entodinium group (81.1%). Protozoa were not detected in the rumen epithelium. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that rumen fluid and solid tissues contain different protozoan populations that may play specific roles in rumen function. Quantitative PCR techniques and a more specific set of phylogenetic probes that distinguish between protozoan species are needed to determine the significance of newly identified groups and to determine the distribution of identified protozoan clusters in rumen microbial communities.

Animals↗

Cloning and characterization of ce/8A gene from Rhizobium leguminosarum bv. trifolii 1536.

AIMS: To isolate the cellulase gene from Rhizobium leguminosarum bv. trifolii 1536. METHODS AND RESULTS: By the shot-gun method a clone (cel8A) harbouring 3.1 kb genomic DNA fragment from R. leguminosarum bv. trifolii 1536 was obtained. The cel8A gene coded 348 amino acids and it belongs to the glycosyl hydrolase family 8. The molecular mass of Cel8A protein induced from Escherichia coli DH5alpha, appeared to be 35 kDa. The optimum pH and optimum temperature was 7.0, and about 30 degrees C for its enzymatic activity respectively. CONCLUSIONS: R. leguminosarum bv. trifolii 1536 had cel8A gene having an open reading frame of 1047 bp coded for the activity of hydrolyzation of carboxymethyl cellulose. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of celluloytic enzyme by R. leguminosarum bv. trifolii was confirmed, which would play specific roles in rhizobia. Future study should focus on its role in the infection and nodulation phenomena.

Cellulase↗

Determination of the subthreshold state contribution in 13C(alpha,n)16O, the main neutron-source reaction for the s process.

The reaction rate of the stellar reaction 13C(alpha,n)16O, which is currently considered to be the main neutron source for the slow (s) process at low energies, has been rederived using the direct alpha-transfer reaction 13C(6Li,d)17O leading to the subthreshold state at 6.356 MeV in 17O. The contribution of the subthreshold state is found to be much smaller than the currently accepted predictions for the main neutron source of the s process, indicating less of a role of this reaction as the neutron source for the s-process scenario in low-mass stars at the asymptotic giant branch.

Journal Article↗

A double-blind, randomised- placebo, controlled, parallel group, multicentre, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea.

The efficacy and safety of sildenafil was evaluated in a randomiSed, double-blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months duration. A total of 133 patients were randomised at six centres in Korea to receive either sildenafil (50 mg initially, increased if necessary to l00 mg or decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual activity for a period of 8 weeks. At the end of this time, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the International Index of Erectile Function (IIEF) scale, (2) the percentage of successful intercourse attempts, and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P&<0.0001). Treatment-related adverse events occurred in 56.1% of patients receiving sildenafil and 20.9% receiving placebo. The most common adverse events with sildenafil were vasodilatation (flushing), headache and abnormalities in colour vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in this population of Korean men appears similar to that reported in other studies in western populations.

Adult↗

Comparison of skin tests to aeroallergens in Ankara and Seoul.

BACKGROUND: The environment contains many allergenic proteins, and skin test reactivity to aeroallergens may be different among people living in different regions. OBJECTIVE: To compare skin test results of Turkish and Korean patients with respiratory allergies. METHODS: The charts of 304 (160 male, 144 female) patients from Ankara, Turkey, and 208 (111 male, 97 female) patients' charts from Seoul, Korea, who had undergone skin prick tests were reviewed. Skin tests were classified as positive when the allergen-induced wheal size was the same size or larger than that caused by histamine. RESULTS: Grass pollens were found to be major allergens more often in Ankara than in Seoul (74.34% vs. 15.87%, p < 0.001). Skin test reactivities in Ankara were significantly lower (p < 0.001) than in Seoul to weed (6.91% vs. 37.50%) and tree pollens (4.61% vs. 39.42%). Allergic reactions to indoor allergens were significantly higher (p < 0.001) in Seoul than in Ankara: house dust mites (HDM) (83.17% vs. 32.90%), cockroaches (45.67% vs. 1.97%), and cats (17.79% vs. 1.65%). CONCLUSION: Due to the different aeroallergen environment, the positive skin test results were different in both cities: grass pollens were the most common allergens in Ankara, while patients from Seoul reacted more commonly to indoor allergens, especially to HDMs and cockroaches.

Adolescent↗

Detection of ABH blood group antigens in the saliva of Koreans and their stability according to storage of saliva samples.

The purpose of the present study was to identify salivary molecules carrying the ABH blood group antigens in Koreans and to investigate the changes in these antigens according to processing and storage of saliva samples. Secretor or non-secretor phenotypes and salivary components carrying the ABH antigens were identified in 90 subjects, 30 subjects in each ABO blood group, by SDS-PAGE and immunoblotting. Saliva samples were then obtained from 12 secretors-two males and two females in each ABO blood group and aliquots of both fresh saliva samples and their supernatants after centrifugation were stored at room temperature, 4, -20 and -70 degrees C. The same experiments were performed after 1, 3 and 6 months to investigate changes in the blood group antigens. In all 68 secretors, high-molecular-weight salivary mucin (MG1) was found to be the primary carrier of the ABH antigens. A salivary component of approximately 80 kDa also carried H antigen in seven saliva samples of 22 blood type O secretors. The blood group antigens were better detected in centrifuged samples. In saliva samples preserved at room temperature and 4 degrees C, the blood group antigens were either not detected or detected as degraded molecules. No change was found in the blood group antigens in saliva samples preserved at -20 and -70 degrees C for 6 months.

ABO Blood-Group System↗

Comparison of green fluorescent protein expression in two industrial Escherichia coli strains, BL21 and W3110, under co-expression of bacterial hemoglobin.

Vitreoscilla hemoglobin (VHb) has been successfully used to enhance production of foreign proteins in several microorganisms including Escherichia coli. We compared the expression of an oxygen-dependent foreign protein, green fluorescent protein (GFP) under co-expression of VHb in two typical industrial E. coli strains, BL21 (a B derivative) and W3110 (a K12 derivative), which have different metabolic properties. We employed the nar oxygen-dependent promoter for self-tuning regulation of VHb expression due to the natural transition of dissolved oxygen (DO) level during culture. We observed several interesting and differing behaviors in cultures of the two strains. VHb co-expression showed a positive influence on expression, and even on solubility, of GFP in both strains; while strain BL21 had the higher GFP expression level, W3110 showed higher solubility of expressed GFP. GFP expression in strain BL21 was very largely affected by variation of aeration environments, but W3110 was not significantly impacted. We surmised that this arose from different oxygen utilization abilities and indeed the two strains showed different patterns of oxygen uptake rate. Interestingly, the VHb co-expressing W3110 strain exhibited a peculiar increasing pattern of GFP expression during the late culture period even under low aeration conditions and this enhancement was more obvious in large-scale cultures. Therefore, this strain could be successfully employed in practical large-scale production cultures where DO levels tend to be limited.

Culture Media↗

Gamma-interferon and soluble interleukin 2 receptor in tuberculous pleural effusion.

To analysis the difference between systemic and local pleural T cell response in pulmonary tuberculosis, we analyzed interferon (IFN)-gamma and soluble interleukin-2 receptor (sIL-2R) in peripheral blood mononuclear cells (PBMC) culture supernatants and in pleural effusion (PE). We also investigated the association of pleural INF-gamma and sIL-2R levels with development of residual pleural thickening (RPT). The subjects in this study included patients with active pulmonary tuberculosis with or without PE (n = 46), those with nontuberculous PE (n = 32), and healthy tuberculin reactors (n = 20). Measurement of IFN-gamma and sIL-2R were made by ELISA. In pulmonary tuberculosis, IFN-gamma and sIL-2R concentrations in PBMC culture supernatants were lower than those of healthy tuberculin reactors (IFN-gamma; 258.4 +/-111.5 pg/mL versus 2792.5 +/-633.2 pg/mL, sIL-2R; 1465.0 +/-144.4 pg/mL versus 4777.1 +/-178.5 pg/mL, p < 0.05), whereas IFN-gamma and sIL-2R concentrations in PE were higher than those from nontuberculous pleural effusion (IFN-gamma; 1154.4 +/-252.4 pg/mL versus 292.0 +/-68.9 pg/mL, sIL-2R; 9805.2 +/-978.9 pg/mL versus 3426.7 +/-695.6 g/mL, p < 0.05). IFN-gamma and sIL-2R in PBMC culture supernatants were significantly lower in tuberculat patients with PE than those without PE, and the patients with a high value of IFN-gamma or sIL-2R in PE showed a low value of IFN-gamma or sIL-2R in PBMC culture supernatant, respectively. Patients with RPT had significantly higher IFN-gamma and sIL-2R values in their PE compared with those without RPT. These findings suggest that diminished systemic Th1 response in tuberculosis results from the accumulation of activated Th1 cell to the disease site, and that levels of IFN-gamma and sIL-2R in PE are useful posttreatment markers of RPT.

Adolescent↗

High prevalence of current asthma and active smoking effect among the elderly.

BACKGROUND: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted. OBJECTIVE: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population. METHODS: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens. RESULTS: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1). CONCLUSION: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

Adult↗

Relation of airway reactivity and sensitivity with bronchial pathology in asthma.

Airway hyperresponsiveness in asthmatics, which may result from inflammation or remodeling, is expressed as the concentration of methacholine that causes a 20% fall in FEV1 in the concentration-response curve (PC20). A decrease in PC20 may be due to a steeper curve (hyperreactivity) and/or a curve shift to the left (hypersensitivity). Our purpose was to analyze the relation of airway sensitivity and reactivity to airway pathological changes. The PC6, as sensitivity parameter, and the slope between PC20 and PC40 as reactivity parameter, were calculated. Total and differential cell counts in the bronchoalveolar lavage fluid, and percentage of epithelial shedding, basement membrane thickness, and submucosal thickness on bronchial biopsy, were measured. The PC6 showed a correlation with the baseline FEV1%. The slope was significantly correlated with the basement membrane thickness, and also demonstrated a strong association with submucosal thickness. The PC20 showed a correlation with the baseline FEV1% and the degree of epithelial shedding. These results suggest that the airway sensitivity and reactivity measurements reflect the degree of airway caliber and remodeling, respectively.

Adolescent↗

Morganelliasis pneumonia in a captive jaguar.

Suppurative bronchopneumonia was discovered in a 6-yr-old male jaguar (Panthera onca onca) that died after a 1 wk history of anorexia, depression, and respiratory difficulty. Morganella morganii was isolated as a pure culture from the lung, spleen, and heart blood. This is the first record of M. morganii induced pneumonia in a jaguar.

Animals↗

La autoantigen enhances translation of BiP mRNA.

Translational initiation of the human BiP mRNA is directed by an internal ribosomal entry site (IRES) located in the 5'-untranslated region (5'-UTR). In order to understand the mechanism of the IRES-dependent translation of BiP mRNA, cellular proteins interacting with the BiP IRES were investigated. La autoantigen, which augments the translation of polioviral mRNA and hepatitis C viral mRNA, bound specifically to the second half of the 5'-UTR of the BiP IRES and enhanced translation of BiP mRNA in both in vitro and in vivo assays. This finding suggests that cellular and viral IRESs containing very different RNA sequences may share a common mechanism of translation.

5' Untranslated Regions↗

5,6-Diphenylpyridazine derivatives as acyl-CoA:cholesterol acyltransferase inhibitors.

Alkyl-5,6-diphenylpyridazine derivatives combining several main features of ACAT inhibitors, such as a long alkyl side chain linked to a heterocycle and the o-diphenyl system, were synthesized and tested. Moreover, modeling studies on representative terms were performed. Some compounds displayed ACAT inhibition in the micromolar range, both on the enzyme isolated from rat liver microsomes and in cell-free homogenate of murine macrophages.

Animals↗

Inhibition of microsomal ATPases by high concentration of Mg2+ in tracheal epithelial cells.

Previous work in our laboratory established the presence of two types of microsomal ATPases, a low-affinity vanadate-sensitive (LAVS) and a high-affinity vanadate-sensitive (HAVS) ATPases, in tracheal epithelial cells. These ATPases were identified as Ca2+-ATPases by specific inhibitors and microsomal Ca2+ uptakes. Since the regulatory roles of Mg2+ on both cellular Ca2+-signaling and epithelial transports were demonstrated, the effects of Mg2+ on these ATPases were investigated. Mg2+-dependence of ATPase activity appeared bell-shaped with a maximal activity at 1-2 mM Mg2+ and Mg2+ at higher than 2 mM inhibited these enzymes. In a kinetic analysis of the LAVS ATPase inhibition, high concentration of Mg2+ appeared to inhibit the binding of ATP to a substrate-binding site. The microsomal 45Ca2+ uptakes mediated by both ATPases were also inhibited by high concentration of Mg2+. In order to test whether high concentration of Mg2+ directly inhibits these enzymes, microsomes were made leaky by the treatment of Triton X-100 and the microsomal ATPases were solubilized with CHAPS. The leaky microsomal ATPases and CHAPS-solubilized ATPases were similarly inhibited by high concentration of Mg2+, suggesting that Mg2+ directly inhibit these enzymes. In conclusion, Mg2+ has two types of modulatory effects on these enzymes, a catalytic effect at low concentration and an inhibitory effect at high concentration.

Adenosine Triphosphatases↗

Xenobiotic response in humanized double transgenic mice expressing tetracycline-controlled transactivator and human CYP1B1.

The cytochrome P450 enzymes (P450s or CYPs) are a superfamily of hemeproteins that catalyze the monooxygenation of a wide range of endobiotic and xenobiotic substrates. A typical strategy in toxicological research and testing involves applying a toxicant at high doses for a short period to homogeneous animals under controlled conditions. However, the conditions of this approach have very little in common with actual human exposure. Transgenic (Tg) mice carrying human genes encoding a drug-metabolizing enzyme (CYP) offer a solution to many of the difficulties in the evaluation of chemical toxicity. It has been demonstrated that the expression of human CYP transgenes under the control of mammalian-inducible promoters exhibits relatively poor fold increases after induction. In this study, we used the tetracycline-regulated (tet) promoter system to increase the expression of the human CYP1B1 (hCYP1B1) gene in the tissues of transgenic mice. By mating two lineages of transgenic mice, double transgenic (dTg) mice expressing both tTA and hCYP1B1 genes under the control of the tet promoter were successfully produced, into which the two transgenes were introduced in an embryo. The expression pattern of tTA-driven hCYP1B1 transgene featured a fold induction of more than 3 to 12 in the brain, heart, and lung and 2- to 4-fold induction in the liver, kidney, and intestine upon doxycycline removal. Immunohistochemical staining with hCYP1B1 antibody was also increased by the removal of doxycycline. In addition, the activities of CYP liver microsomes in the dTg mice without doxycycline showed an increase compared to that in the dTg mice treated with doxycycline. The level of activities correspond to the levels of human CYP1B1 protein expression in the Tg mice (-dox) that was increased by 2-fold induction as compared to that of the dTg mice with doxycycline. Thus, overproduction in Tg can be purified and the activity of purified human CYP1B1 can be characterized by alterations to the coding sequence in order to solve the physiological function of this enzyme in a humanized in vivo system. It is also possible to examine the activity of purified human CYP1B1 using several environmental toxicants such as procarcinogens.

Animals↗

A novel mechanism for myocardial stunning involving impaired Ca(2+) handling.

The mechanism of myocardial stunning has been studied extensively in rodents and is thought to involve a decrease in Ca(2+) responsiveness of the myofilaments, degradation of Troponin I (TnI), and no change in Ca(2+) handling. We studied the mechanism of stunning in isolated myocytes from chronically instrumented pigs. Myocytes were isolated from the ischemic (stunned) and nonischemic (normal) regions after 90-minute coronary stenosis followed by 60-minute reperfusion. Baseline myocyte contraction was reduced, P<0.01, in stunned myocytes (6.3+/-0.4%) compared with normal myocytes (8.8+/-0.4%). The time for 70% relaxation was prolonged, P<0.01, in stunned myocytes (131+/-8 ms) compared with normal myocytes (105+/-5 ms). The impaired contractile function was associated with decreased Ca(2+) transients (stunned, 0.33+/-0.04 versus normal, 0.49+/-0.05, P<0.01). Action potential measurements in stunned myocytes demonstrated a decrease in plateau potential without a change in resting membrane potential. These changes were associated with decreased L-type Ca(2+)-current density (stunned, -4.8+/-0.4 versus normal, -6.6+/-0.4 pA/pF, P<0.01). There were no differences in TnI, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), and phospholamban protein quantities. However, the fraction of phosphorylated phospholamban monomer was reduced in stunned myocardium. In rats, stunned myocytes demonstrated reduced systolic contraction but actually accelerated relaxation and no change in Ca(2+) transients. Thus, mechanisms of stunning in the pig are radically different from the widely held concepts derived from studies in rodents and involve impaired Ca(2+) handling and dephosphorylation of phospholamban, but not TnI degradation.

Action Potentials↗

Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells.

cis-platinum(II) (cis-diammine dichloroplatinum; cisplatin) is a potent antitumor compound that is widely used for the treatment of many malignancies. An important side-effect of cisplatin is nephrotoxicity, which results from injury to renal tubular epithelial cells and can be manifested as either acute renal failure or a chronic syndrome characterized by renal electrolyte wasting. Recently, apoptosis has been recognized as an important mechanism of cell death mediating the antitumor effect of cisplatin. This study was undertaken to examine the mechanisms of cell death induced by cisplatin in M-1 cells, which were derived from the outer cortical collecting duct cells of SV40 transgenic mice. Treatment of M-1 cells with high concentrations of cisplatin (0.5 and 1 mM) for 2 hr led to necrotic cell death, whereas a 24-hr treatment with 5-20 microM cisplatin led to apoptosis. Antioxidants protected against cisplatin-induced necrosis, but not apoptosis, indicating that reactive oxygen species play a role in mediating necrosis but not apoptosis induced by cisplatin and that the mechanism of cell death induced by cisplatin is concentration dependent. The low concentrations of cisplatin, which induced apoptosis in M-1 cells, did not affect the expression levels of Bcl-2-related proteins and did not activate c-Jun NH2-terminal kinase (SAPK/JNK). Cisplatin induced the translocation of endogenous Bax from the cytosolic to the membrane fractions and, subsequently, the release of cytochrome c. Overexpression of Bcl-2 blocked cisplatin-induced apoptosis and Bax translocation. These observations suggest that the subcellular redistribution of Bax is a critical event in the apoptosis induced by cisplatin.

Animals↗