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Biomedical subjects

Y D Kim

Publications and source records attributed to Y D Kim.

At least 19 recordsLinked to original sources

Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter.

Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats with hemagglutinating virus of Japan-envelope (HVJ-E) vectors containing Epstein-Barr virus (EBV) plasmids encoding the genes for insulin and the GLUT 2 transporter. Efficient delivery of the genes was achieved with the HVJ-E vector, and the use of the EBV replicon vector led to prolonged hepatic gene expression. Blood glucose levels were normalized for at least 3 weeks as a result of the gene therapy. Cotransfection of GLUT 2 with insulin permitted the diabetic rats to regulate their blood glucose levels upon exogenous glucose loading in a physiologically appropriate manner and improved postprandial glucose levels. Moreover, cotransfection with insulin and GLUT 2 genes led to in vitro glucose-stimulated insulin secretion that involved the closure of K(ATP) channels. The present study represents a new way to efficiently deliver insulin gene in vivo that is regulated by ambient glucose level with prolonged gene expression. This may provide a basis to overcome limitations of insulin gene therapy in humans.

Animals↗

Appearance of bulk properties in small tungsten oxide clusters.

Contrary to the conventional understanding that atomic clusters usually differ in properties and structure from the bulk constituents of which they are comprised, we show that even a dimer of tungsten oxide (WO(3))(2) possesses bulklike features and the geometry of a small cluster containing only 4 tungsten and 12 oxygen atoms bears the hallmarks of crystalline tungsten oxide, WO(3). This observation, based on a synergistic approach involving mass distributions under quasisteady state conditions, photoelectron spectroscopy, and first principles molecular orbital theory, not only illustrates the existence of a class of strongly covalent or ionic materials whose embryonic forms are tiny clusters but also lends the possibility that a fundamental understanding of complex processes such as catalytic reactions on surfaces may be achieved on an atomic scale with clusters as model systems.

Journal Article↗

Plant regeneration from hairy-root cultures transformed by infection with Agrobacterium rhizogenes in Catharanthus roseus.

Hypocotyl explants of Catharanthus roseus produced hairy roots when cultured on Murashige and Skoog (MS) basal medium after infection by Agrobacterium rhizogenes. Explants gave rise to adventitious shoots at a frequency of up to 80% when cultured on MS medium supplemented with 31.1 microM 6-benzyladenine and 5.4 microM alpha-naphthaleneacetic acid. There was a significant difference in the frequency of adventitious shoot formation for each hairy-root line derived from a different cultivar. Plants derived from hairy roots exhibited prolific rooting and had shortened internodes. Approximately half of the plants had wrinkled leaves and an abundant root mass with extensive lateral branching, but otherwise appeared morphologically normal. Plants with hairy roots that were derived from the cultivar Cooler Apricot developed flowers with petals that were white in the proximal region, whereas the wild-type flower petals are red. PCR and Southern blot analyses revealed that plants derived from hairy roots retained the Ri TL-DNA.

Adenine↗

Transcription factor decoy for AP-1 reduces mesangial cell proliferation and extracellular matrix production in vitro and in vivo.

Diabetic nephropathy is characterized by an expansion of glomerular mesangium, caused by mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins, which eventually leads to glomerulosclerosis and renal failure. Activator protein-1 (AP-1), a transcription factor, is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation and ECM production. This investigation was undertaken to test the hypothesis that AP-1 plays an important role in ECM gene expression, and to develop a molecular therapeutic strategy based on decoy oligodeoxynucleotides (ODN). In this report, we show that transfection with AP-1 decoy ODN strongly inhibits high glucose- and angiotensin II-induced cell proliferation and expression of ECM genes in cultured mesangial cells in vitro. Administration of AP-1 decoy ODN into streptozotocin-induced diabetic rat kidney in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually abolished TGF-beta1 and plasminogen activator inhibitor-1 expression. Our results collectively indicate that AP-1 activation is crucial for mesangial cell proliferation and ECM production in response to high glucose and angiotensin II. Moreover, use of stable AP-1 decoy ODN combined with the highly effective HVJ-liposome method provides a novel potential molecular therapeutic strategy for the prevention of diabetic nephropathy.

Angiotensin II↗

Proton energy spectra in the nonmesonic weak decay of 12lambdaC and 28lambdaSi hypernuclei.

Numbers of protons per Gamma hypernuclear weak decay were measured as a function of proton energy above 40 MeV, explicitly identifying production of Gamma hypernuclei by the (pi+,K+) reaction. The ratios between the neutron-stimulated to proton-stimulated nonmesonic decay widths, Gamma((Lambda)n-->nn)/Gamma((Lambda)p-->np) ( = Gamma(n)/Gamma(p)) were extracted by fitting the proton energy spectra. The present result claims that the proton yields are suppressed and the Gamma(n)/Gamma(p) ratios are close to 1 both for 12LambdaC and 28LambdaSi in contradiction to theoretical expectations based on meson exchange models.

Journal Article↗

Stable sol-gel microstructured and microfluidic networks for protein patterning.

We demonstrate the formation of micropatterned sol-gel structures containing active proteins by patterning with polydimethylsiloxane (PDMS) microchannels. To transport sol solution efficiently into the hydrophobic PDMS microchannels, a hydrophilic-hydrophobic block copolymer was used to impart hydrophilicity to the PDMS microchannels. Poor adhesion of the micropatterned gel structure onto glass slides was improved by treating the glass surface with a polymeric substrate. To minimize cracks in the gel microstructure, hybrid matrices of interpenetrating organic and inorganic networks were prepared containing the reactive organic moieties polyvinylalcohol or polyvinylpyrrolidone. Retention of biochemical activity within the micropatterned gel was demonstrated by performing immunobinding assays with immobilized immunoglobulin G (IgG) antibody. The potential application of microfluidics technology to immobilized-enzyme biocatalysis was demonstrated using PDMS-patterned microchannels filled with trypsin-containing sol-gels. This work provides a foundation for the microfabrication of functional protein chips using sol-gel processes.

Catalysis↗

Measurement of the B(e2) of (7)(lambda)Li and shrinkage of the hypernuclear size.

We report on the first measurement of a hypernuclear gamma-transition probability. gamma rays emitted in the E2(5/2(+)-->1/2(+)) transition of (7)(Lambda)Li were detected by a large-acceptance germanium detector array (Hyperball), and the lifetime of the parent state ( 5/2(+)) was determined by the Doppler shift attenuation method. The obtained result, 5.8(+0.9)(-0.7)+/-0.7 ps, was then converted into the reduced transition probability [ B(E2)] to be B(E2;5/2(+)-->1/2(+)) = 3.6+/-0.5(+0.5)(-0.4) e(2) fm(4). Compared with the B(E2) of the corresponding E2(3(+)-->1(+)) transition in the 6Li nucleus, our result gives evidence that the size of the 6Li core in (7)(Lambda)Li is smaller than the 6Li nucleus in the free space.

Journal Article↗

Clinical and anatomical factors associated with thalamic dyskinesias.

To define the clinical and anatomical factors associated with dyskinesias following thalamic infarction, we performed neurological examination and three-dimensional brain magnetic resonance imaging for 23 patients with thalamic infarction. We measured the total volumes and the largest diameters of the lesions on axial and coronal images. Using the atlas of human thalamus, we investigated the damaged thalamic nuclei. We compared the means of the volumes and the largest diameters of the lesions, and the frequencies of damaged thalamic nuclei between patients with and without thalamic dyskinesias. Seven (two pseudochoreoathetosis and five dystonia) of the 23 patients with thalamic infarction developed dyskinesias. No specific neurological deficits at the onset of stroke predicted the development of dyskinesias. The mean volume of the lesions of patients with dyskinesias (739 mm(3)) was significantly larger than that of those without dyskiensias (92.9 mm(3)). The means of the largest axial (11.6 mm) and coronal (10.8 mm) diameters were significantly larger in patients with dyskinesias, compared to those (axial, 7.1 mm; coronal, 6.4 mm) of patients without dyskinesias. Patients with dyskinesias had damage in the centromedian (CM) thalamic nucleus more frequently compared to those without dyskinesias. Patients with a large thalamic infarction involving the CM nucleus are more likely to develop dyskinesias.

Adult↗

Combined right transradial coronary angiography and selective carotid angiography: safety and feasibility in unselected patients.

We evaluated the safety and feasibility of ad hoc carotid angiography following the right transradial coronary angiography. Selective carotid angiography was performed subsequent to coronary angiography in 213 consecutive patients. A 5 Fr Simmons catheter was reformed in descending or ascending aorta, then, withdrawn and rotated to cannulate the left and right carotid artery. Both carotid angiography was performed selectively in 211 (99%) patients. In two patients with severely tortuous subclavian artery, selective cannulation of the left carotid artery failed. There was no thromboembolism or arterial dissection. After the learning phase of 50 patients, the time to reform the catheter in aorta and to cannulate the left and right carotid artery was 50 +/- 77, 66 +/- 68, and 58 +/- 57 sec, respectively. Total procedural time was 195 +/- 145 sec. In conclusion, ad hoc carotid angiography can be performed reliably and safely following the right transradial coronary angiography. It might be useful for evaluation of an isolated or associated carotid artery stenosis. Cathet Cardiovasc Intervent 2001;53:380-385.

Adolescent↗

Urinary 1-hydroxypyrene and 2-naphthol concentrations in male Koreans.

OBJECTIVE: Urinary 1-hydroxypyrene (1-OHP) has been used as a biological marker of exposure to polycyclic aromatic hydrocarbons (PAHs), and urinary 2-naphthol is suggested as a new marker for route-specific exposure to airborne PAHs. We analyzed urinary 1-OHP and 2-naphthol concentrations in 292 male Koreans (129 university students and 163 shipyard workers) to define the distribution pattern in Koreans with no or low occupational exposure to PAHs. METHOD: Histories of cigarette smoking and the eating of PAH-containing foods were obtained by a self-administered structured questionnaire. Urine samples were collected and urinary 1-OHP and 2-naphthol concentrations were measured using high-performance liquid chromatography (HPLC). RESULTS: The arithmetic (geometric) means of urinary 1-OHP and 2-naphthol concentrations for all students, expressed as micromoles per mole of creatinine, were 0.04 (0.04) and 3.12 (2.22), for non-smokers 0.03 (0.03) and 1.78 (1.30) and for smokers 0.05 (0.03) and 4.36 (3.62), respectively. Among shipyard workers, the arithmetic (geometric) means of urinary 1-OHP and 2-naphthol concentrations were 0.69 (0.31) and 4.37 (2.62) for all, 0.27 (0.18) and 2.46 (1.16) for nonsmokers, and 0.97 (0.44) and 5.60 (4.44) for smokers, respectively. Mean urinary 1-OHP and 2-naphthol concentrations differed significantly between nonsmokers and smokers both in students and in shipyard workers. In smokers, some variables related to smoking habit were positively correlated with urinary 1-OHP and with 2-naphthol concentrations. The latter showed better correlations with the variables related to smoking amount than the former. None of the food-related factors was significantly correlated with urinary 1-OHP or 2-naphthol concentration. CONCLUSION: These results suggest that urinary 2-naphthol concentration is more sensitively affected by smoking status than urinary 1-OHP concentration and that urinary 2-naphthol is a sensitive marker for low-level inhalation of PAHs.

Chromatography, High Pressure Liquid↗

P16INK4a protein expression is associated with poor survival of the breast cancer patients after CMF chemotherapy.

Immunohistochemical assay for p16 protein expession was performed in 192 breast carcinoma patients treated with adjuvant chemotherapy. p16 expression was observed in 78 cases (40.6%). The frequency of p16 expression significantly decreased in moderately differentiated (histologic grade II) cancers, 20 (19.6%) of 102. In poorly differentiated cancers (histologic grade III), p16 expression was not observed in all 16 cases. p16 expression was significantly associated with histologic grade of the breast carcinomas (p < 0.001). The proliferative index (PI: S + G2/M) of individual tumors was measured by DNA flow cytometry. In 114 tumors with PI less than 20%, p16 expression was observed in 59 tumors (49.1%). In the tumors with PI equal or more than 20%, p16 expression was observed in 22 (28.2%) of 78 cases. p16 expression was significantly decreased in the tumor with higher PI (p =0.003). For the other clinicopathologic variables, no significant association was found with p16 expression status. Immunohistochemical assay for p53 protein expression was performed on the same breast carcinomas. There was no significant association between p16 and p53 expression in breast carcinomas. During median follow-up period of 52 months (range: 40-72 months), 46 patients (25.8%) had recurrent disease and 32 patients (18.91%) died of recurrent disease. p16 expression was observed in 20 (43.5%) of 46 patients with recurrent disease, while its expression was observed in 58 patients (39.7%) of 146 patients who were free of recurrence during the study period. p16 expression had no significant impact on predicting recurrence of breast carcinoma. Fourteen patients (12.2%) of 114 patients whose tumors did not show p16 expression died of recurrent breast carcinoma, whereas 18 patients (23.1%) of 78 patients with p16 expressing tumor died during the follow-up period. There was a significant difference of patient survival according to p16 expression status (p = 0.039). These results indicate that p16 expression is useful in predicting response to chemotherapy in breast cancer patients. p16 protein seems to have a role in tumor growth and differentiation of the breast carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1, GSTM1 and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentrations.

This study was undertaken to determine the effects of occupation, lifestyle and the genetic polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1 (CYP2E1) and glutathione S-transferases micro1 (GSTM1) and 1 (GSTT1) on the concentrations of urinary 1-hydroxypyrene (1-OHP) and 2-naphthol among Korean coke oven workers and university students. The study subjects included 90 coke oven workers and 128 university students. A questionnaire was used to obtain detailed data about the work area, smoking habits and food intake of subjects. Associations between urinary polycyclic aromatic hydrocarbon (PAH) concentrations and occupation, smoking status, total airborne PAH level and genetic polymorphisms were tested. Urinary 1-OHP and 2-naphthol concentrations were higher in coke oven workers than in students and correlated significantly with work area. Urinary 2-naphthol concentrations increased with an increase in the level of cigarette smoking in students. Total airborne PAH level correlated with urinary 1-OHP concentration in coke oven workers. Urinary 1-OHP and 2-naphthol concentrations were higher in coke oven workers with the c1/c2 or c2/c2 genotype of CYP2E1 than in those with the c1/c1 genotype. Urinary 2-naphthol concentrations were higher in GSTM1-null workers than in GSTM1-positive workers. In multiple regression analysis CYP2E1 was a significant factor determining urinary 1-OHP concentrations in coke oven workers. CYP2E1 and GSTM1 were significant determinants for urinary 2-naphthol concentrations in coke oven workers and GSTM1 and smoking were prognosticators among university students. Urinary 1-OHP is a better indicator of occupational exposure to PAH in coke oven workers than 2-naphthol, whereas urinary 2-naphthol may be more sensitive for non-occupational inhalation exposure to PAH. In occupationally exposed populations CYP2E1 and GSTM1 appear to play an important role in the metabolism of pyrene and naphthalene. In individuals not occupationally exposed to PAHs GSTM1 and smoking seem to influence the urinary concentration of 2-naphthol.

Base Sequence↗

Nonselective left internal mammary artery angiography during right transradial coronary angiography: a simple, rapid, and safe technique.

Internal mammary artery angiography is increasingly required, but the technique for left internal mammary artery (LIMA) angiography during right transradial coronary angiography is not well established. The authors investigated the feasibility and safety of a new, simple, and rapid nonselective technique. Following right transradial coronary angiography, LIMA angiography was performed using a 5 French (Fr) Judkins JL-3.5 catheter in 110 patients. The catheter, placed in the ascending aorta with its natural curve, was withdrawn slowly while being rotated clockwise to engage its tip in the proximal left subclavian artery. Contrast material was injected while sphygmomanometer cuff inflation was applied to the left upper arm. In the last 50 patients, the angiography was performed twice randomly with and without the cuff inflation. In 108 patients (98%), the catheter was successfully engaged in the subclavian artery in a mean of 11 +/- 8 seconds (range, 3-136) from the time when it was withdrawn from the ascending aorta, and nonselective LIMA angiography was successfully performed. The image quality of the angiograms was satisfactory in 103 (95%) of the 108 patients. In the last 50 patients, the image quality of the angiograms was determined satisfactory in 48 (96%) and 45 (90%) patients, with and without the cuff inflation, respectively. The difference was statistically not significant. There were no complications, including arterial dissection and thromboembolism. In conclusion, nonselective LIMA angiography can be readily and safely performed during right transradial coronary angiography using a 5 Fr Judkins JL-3.5 catheter.

Aged↗

The central conduction time in posterior tibial and pudendal nerve somatosensory evoked potentials.

The somatosensory evoked potentials (SEPs), following stimulation of both the posterior tibial nerve (PTSEP) and pudendal nerve (PNSEP), comprise of the lumbar negative, subcortical and cortical potential. These can be used to assess the long somatosensory pathway, including peripheral, intraspinal and intracranial conduction along the entire length. This study aimed to compare the central conduction time between the PTSEP and the PNSEP, and to investigate the relationship between the intraspinal and intracranial conduction time in the SEP pathway. The SEPs following stimulation of the posterior tibial nerve at the ankle and the pudendal nerve at the shaft of the penis were analyzed in 20 normal male subjects. The central conduction of the PNSEP was found to be slower than that of the PTSEP (p <0.05). This difference is due to a delay in conduction rather than that of intracranial conduction.

Adolescent↗

Phylogenetic relationships in family Magnoliaceae inferred from ndhF sequences.

The ndhF sequences of 99 taxa, representing all sections in extant Magnoliaceae, were analyzed to address phylogenetic questions in the family. Magnolia macrophylla and M. dealbata, North American species of Magnolia section Rytidospermum, are placed at the base in the subfamily Magnolioideae although its supporting value is low. In the remaining taxa, several distinctive lineages are recognized: (1) Magnolia, the biggest genus in the family, is not monophyletic; (2) Michelia, including section Maingola of Magnolia subgenus Magnolia, is closely related with Elmerrillia and sections Alcimandra and Aromadendron of Magnolia subgenus Magnolia; (3) the associates of Michelia are grouped with Magnolia subgenus Yulania and section Gynopodium of Magnolia subgenus Magnolia; (4) Pachylarnax forms a clade with sections Manglietiastrum and Gynopodium of Magnolia; (5) a well-supported Manglietia clade is recognized; (6) Caribbean species of section Theorhodon of Magnolia subgenus Magnolia, which are section Splendentes sensu Vázquez-Garcia, are closely allied with New World members of Magnolia subgenus Talauma; and (7) section Rytidospermum of Magnolia subgenus Magnolia and subgenus Talauma are polyphyletic. The separated clades in the molecular tree are considerably different from traditional taxonomic dispositions in the family. The molecular data strongly suggest that a taxonomic realignment of infrafamilial delimitations and compositions should be considered.

Journal Article↗

Regulation of IL-1beta-mediated MUC2 gene in NCI-H292 human airway epithelial cells.

This study demonstrates for the first time the effects of IL-1beta on the regulation of protein production as well as MUC2 gene transcription in cultured human airway epithelial cells. The effect of IL-1beta on the regulation of MUC2 protein was determined by flow cytometric analysis. The expression level of MUC2 induced by IL-1beta increased in a dose-dependent manner. MUC2 transcripts were detected after 2 h of exposure to IL-1beta and reached maximal level after 8 h. Actinomycin D experiments indicated that the IL-1beta-mediated MUC2 expression was controlled by transcriptional regulation. Both RT-PCR and FACS analysis showed that budesonide concomitantly attenuated IL-1beta mediated MUC2 gene as well as protein production levels. Use of the glucocorticoid receptor antagonist, RU-486, restored the inhibitory effect of budesonide on the IL-1beta-mediated MUC2 protein as well as gene. The data suggest that IL-1beta up-regulates MUC2 gene by transcriptional regulation and that budesonide suppresses the IL-1beta-medicated MUC2 expression via decreased transcriptional activation.

Bronchodilator Agents↗

Observation of a spin-flip M1 transition in 7(lambda)Li.

Using a large-acceptance germanium detector array (Hyperball), we have observed a spin-flip M1 gamma transition between the ground-state spin doublet of (7)(Lambda)Li (3/2(+)-->1/2(+)). The observed energy of 691.7+/-0.6(stat)+/-1.0(syst) keV provides crucial information on the strength of the spin-spin interaction between a Lambda and a nucleon. This is the first observation of well-identified hypernuclear gamma transitions using germanium detectors.

Journal Article↗