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Biomedical subjects

J M Song

Publications and source records attributed to J M Song.

At least 19 recordsLinked to original sources

Roles of NF-kappaB and bcl-2 in two differential modes of cell death of mouse cortical collecting duct cells.

Recent data have implicated nuclear factor-kappaB (NF-kappaB) and Bcl-2 in the regulation of apoptotic and necrotic cell death in various cells. However, mechanisms of their effects on cell death of renal epithelial cells are not clear. First, we investigated the effect of specific inhibition of NF-kappaB and overexpression of Bcl-2 on necrotic cell death induced by hydrogen peroxide or cisplatin in renal collecting duct cells. M-1 cells, which were derived from outer cortical collecting duct, were stably transfected with the non-phosphorylatable mutant of inhibitory-kappaBalpha (I-kappaBalpha) and Bcl-2. Overexpression of I-kappaBalpha and Bcl-2 did not affect cisplatin-induced necrotic cell death, but overexpression of I-kappaBalpha significantly decreased H2O2-induced cell death. Regarding apoptotic cell death induced by cisplatin, serum deprivation and contact inhibition was increased by overexpression of I-kappaBalpha, whereas overexpression of bcl-2 inhibited the apoptotic cell death. I-kappaBalpha overexpression increased Bax expression and decreased cIAP-1 and -2 expression compared to vector-transfected cells, but did not alter SAPK/JNK activity in the presence or absence of cisplatin. NF-kappaB activity was significantly higher in bcl-2-overexpressing cells than in control cells. These data show that activation of NF-kappaB mediates H2O2-induced necrotic injury, but inhibits apoptotic cell death in renal collecting duct cells, and that Bcl-2 selectively protects apoptotic cell death in M-1 cells.

Animals↗

Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis.

In this work, the development and applications of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo disease diagnosis including oral carcinoma are described. The optical diagnosis system was based on an OPO laser for multi-wavelength excitation and time-resolved detection. The pulsed Nd-YAG-pumped OPO laser system (6 ns, 20 Hz) is compact and has a rapid, broad, and uniform tuning range. Time-gated detection of intensified charge-coupled device (ICCD) making use of external triggering was used to effectively eliminate the laser scattering and contribute to the highly sensitive in vivo measurements. Artificial tissue-simulating phantoms consisting of polystyrene microspheres and tissue fluorophores were tested to optimize the gating parameters. 51-ns gate width and 39-ns gate delays were determined to be the optimal parameters for sensitive detection. In vivo measurements with the optical diagnosis system were applied to esophagus, stomach, and small intestine using an endoscope in canine animal studies. The rapid tuning capability of the optical diagnosis system contributed greatly to the optimization of wavelength for the observation of porphyrin in the small intestine. When the small intestine was thoroughly washed with water, the emission band which corresponds to porphyrin disappeared. Based on this observation, it was concluded that the detected signal was yielded by porphyrin-containing bile secretion. Also, multispectral analyses using multiple excitations from 415 to 480 nm at 5 nm intervals confirmed the porphyrin detection in the small intestine. The optical diagnosis system was also applied to the detection of human xenograft of oral carcinoma in mice using 5-aminolevulinic acid (5-ALA) which is a photodynamic therapy (PDT) drug. Significant differences in protoporphyrin IX fluorescence intensity between normal and tumor tissue could be obtained 2 hours after the injection of 5-ALA into mice due to the preferential accumulation of 5-ALA in tumors. Results reported herein demonstrate potential capabilities of the LIF-OPO system for in vivo disease diagnosis.

Animals↗

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↗

Optimization of DNA electrophoretic behavior in poly(vinyl pyrrolidone) sieving matrix for DNA sequencing.

Poly(vinyl pyrrolidone) solution was used as a separation matrix in capillary electrophoresis for DNA sequencing. Four-label four-color detection was performed for base calling. Dye-labeled DNA showed large mobility shifts at normal conditions for DNA separation. Temporal correction of mobility shifts was achieved by normalizing with respect to pure peaks that are without spectral interference or temporal overlap at each color channel. To achieve even better performance, a DNA separation condition that does not require corrections for mobility shifts was found. Dichlororhodamine-labeled DNA fragments showed ideal electrophoretic behaviors according to DNA size in the presence of 10 M urea. The base-calling accuracy of dichlororhodamine-labeled M13mp18 and PGEM/U DNA were 99.3% for 333 bases and 99% for 315 bases, respectively. Base calling of unknown DNA samples obtained in the presence of 10 M urea showed 99.1% accuracy.

Coloring Agents↗

Intravascular ultrasound analysis of beta radiation therapy for diffuse in-stent restenosis to inhibit intimal hyperplasia.

We evaluated the efficacy of beta-radiation therapy ((188)Re-MAG(3)) to inhibit intimal hyperplasia (IH) in diffuse in-stent restenosis by intravascular ultrasound (IVUS) analysis in 50 patients. Nine patients who did not agree with radiation therapy, and therefore underwent rotational atherectomy and balloon angioplasty for diffuse in-stent restenosis in the same study period, were selected for control groups. Serial IVUS comparisons were available in 44 of 50 patients with radiation therapy and 7 of 9 control patients. At 6-month follow-up, there was less significant increase of IH area in patients with radiation therapy than in control patients (Delta IH area = 0.1 +/- 0.8 mm(2) vs. 2.6 +/- 1.8 mm(2), P > 0.001 in mean values, and 0.6 +/- 1.4 mm(2) vs. 2.9 +/- 2.1 mm(2), P = 0.026 in values of follow-up lesion site, respectively). In conclusion, beta-radiation therapy might be an effective treatment modality to inhibit intimal hyperplasia in patients with diffuse in-stent restenosis.

Aged↗

Atrial fibrillation surgery simplified with cryoablation to improve left atrial function.

BACKGROUND: The Maze procedure restores atrial fibrillation to normal sinus rhythm. However, concurrent left atrial functional recovery is not always achieved. To address this limitation, a modification using linear cryoablation is described. METHODS: Between July 1997 and December 1999, 83 patients received atrial fibrillation surgery in association with mitral valve surgery with or without additional concurrent procedures by either the conventional technique, group I (n = 30) or the modified technique, group II (n = 53). Onset of sinus conversion and echocardiographic assessment of postoperative left ventricular function, left atrial size, and mitral A-wave velocity were compared in the early postoperative period and 6 months after surgery. RESULTS: Sinus conversion occurred significantly earlier in group II, 2.4 +/- 5 days versus group I, 7.0 +/- 10 days. The mean transmitral A-wave velocity and the incidence of A-wave appearance in the early postoperative period and 6 months postoperatively were greater in group II than group I. CONCLUSIONS: With the current modification, restoration of sinus rhythm and superior left atrial contractile function occurred earlier than with the standard Maze III technique.

Atrial Fibrillation↗

Six-month angiographic follow-up after intravascular ultrasound-guided stenting of infarct-related artery: comparison with non-infarct-related artery.

BACKGROUND: Compared with balloon angioplasty, stenting has been established as an effective treatment modality to reduce restenosis in patients with acute myocardial infarction. However, the immediate results that predict favorable long-term outcomes in the acute infarct stenting are unknown. Therefore, we evaluated long-term outcomes of stenting for infarct-related artery (IRA) lesions by using intravascular ultrasound (IVUS) compared with that of stenting for non-IRA lesions. METHODS: IVUS-guided coronary stenting was successfully performed in 510 native coronary lesions (105 IRA vs 405 non-IRA). A 6-month follow-up angiogram was performed in 419 (82.2%) lesions: 87 (82.9%) IRA lesions and 332 (82.0%) non-IRA lesions. Coronary stenting on the IRA lesions was successfully performed within 7 to 10 days after onset of infarction in 42 patients and within 12 hours in 45 patients. Results were evaluated by clinical, angiographic, and IVUS methods. RESULTS: There were no significant differences in clinical and angiographic variables between the two groups. IVUS variables including reference vessel area and minimal stent area were also similar between the two groups. There was no significant difference in angiographic restenosis rate between the two groups in cases of minimal stent area > or = 7 mm(2): 12.8% (6 of 47) in IRA versus 19.1% (33 of 173) in non-IRA lesions (P = .315). However, the angiographic restenosis rate in cases of minimal stent area <7 mm(2) was 50% (20 of 40) in IRA lesions versus 31.5% (50 of 159) in non-IRA lesions (P = .028). CONCLUSIONS: Angiographic restenosis is significantly higher in stenting for IRA lesions compared with that for non-IRA lesions in cases of minimal stent area < 7 mm(2).

Angioplasty, Balloon, Coronary↗

Effect of hypercholesterolemia on macrophage infiltration after balloon injury to rabbit iliac artery.

Both hypercholesterolemia and vascular injury have been reported to induce macrophage infiltration, but their combined effect and the mechanism by which hypercholesterolemia enhances the infiltration remain to be clarified in vivo. To evaluate the effect of hypercholesterolemia on macrophage infiltration after vascular injury, the iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined 2h, 1 day, 3 days, 7 days, and 14 days after balloon injury using immunohistochemical staining for macrophages, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1. Nuclear factor kappa-B (NF-kappaB) activation was also evaluated in fresh frozen iliac arteries using the electrophoretic mobility shift assay method. The fundamental difference between HC and NC was the amount of macrophage infiltration seen in HC from 7 days after balloon injury. Two out of 4 HC iliac arteries on the 7th day, and 3 out of 4 HC iliac arteries on the 14th day were positively stained with ICAM-1 in regenerated endothelium and neointima, whereas there were no positively stained NC iliac arteries. Neither HC nor NC tissues showed positive staining with VCAM-1. NF-kappaB was activated in HC 7 and 14 days after balloon injury, but not in NC. In conclusion, in vivo hypercholesterolemia induces macrophage infiltration after balloon injury and it is mediated by increased NF-kappaB activation promoting ICAM-1 expression.

Animals↗

Clinical characteristics of constrictive pericarditis diagnosed by echo-Doppler technique in Korea.

A retrospective analysis of clinical data of 71 patients with constrictive pericarditis (CP) diagnosed by echo-Doppler technique (mean age, 49+/-17) was done. In 27 patients (38%), the etiology was unknown, and the three most frequent identifiable causes were tuberculosis (23/71, 32%), cardiac surgery (8/71, 11%), and mediastinal irradiation (6/71, 9%). Pericardiectomy was performed in 35 patients (49%) with a surgical mortality of 6% (2/35), and 11 patients (15%, 11/ 71) showed complete resolution of constrictive physiology with medical treatment. Patients with transient CP were characterized by absence of pericardial calcification, shorter symptom duration, and higher incidence of fever, weight loss, and tuberculosis. The 5-yr survival rates of patients with transient CP and those undergoing pericardiectomy were 100% and 85+/-6%, respectively, which were significantly higher than that of patients without undergoing pericardiectomy (33+/-17%, p=0.0083). Mediastinal irradiation, higher functional class, low voltage in ECG, low serum albumin, and old age were the independent variables associated with a higher mortality. Tuberculosis is still the most important etiology of CP in Korea, and not infrequently, it may cause transient CP. Early diagnosis and decision-making using follow-up echocardiography are crucial to improve the prognosis of patients with CP.

Adult↗

[Clinical study on effect of tongyu no. I in improving prethrombotic state of senile diabetes mellitus].

OBJECTIVE: To explore the therapeutic mechanism of Tongyu No. I (TY-1) in improving prethrombotic state of senile diabetes mellitus. METHODS: Sixty-two patients of diabetes mellitus with prethrombotic state and blood-stasis Syndrome were selected and divided randomly into two groups, 32 in the treated group and 30 in the control group. The two groups were treated by conventional therapy, combined with additional TY-1 (treated group) and aspirin (control group) respectively for 2 months. And the clinical effect as well as relevant criteria in both groups before and after treatment were observed. RESULTS: In the treated group, treatment showed markedly effective in 14 cases, effective in 16 and ineffective in 2, the total effective rate being 93.8%. In the control group, the corresponding values were 6, 14, 10 and 66.7% respectively. Comparison of the total effective rate in the two groups showed significant difference (P < 0.01). After treatment, the treated group showed lowering in plasma TXB2 similar to that in the control group, while the decrease of GMP-140 and fasting blood glucose levels was significant as compared with before treatment (P < 0.01) and the difference was significant between the two groups (P < 0.05) after treatment. CONCLUSION: TY-1 could improve the prethrombotic state and blood-stasis Syndrome in patients of diabetes mellitus, the main therapeutic mechanism might be correlated to the lowering of GMP-140 content.

Aged↗

Alternative base-calling algorithm for DNA sequencing based on four-label multicolor detection.

A simple base-calling scheme based on four-label multicolor detection is suggested for DNA sequencing. The entire spectra of the dye labels were used for identification. Specifically, the maxima of the emission spectra rather than the intensity ratios at selected wavelengths are used to provide excellent discrimination. Capillary gel electrophoresis was used for the separation of DNA fragments. Data acquisition and analysis compatible with fast and high-throughput imaging detection was accomplished. The accuracy of base calling of PGEM/U DNA from the raw data obtained with 5 nm and 7 nm spectroscopic resolution were 98.4% for 386 bases and 98.4% for 385 bases. Base calling of M13mp18 DNA showed 98.3% accuracy for 420 bases.

Algorithms↗

Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation.

This study assessed the clinical utility of mitral annulus velocity in the evaluation of left ventricular diastolic function in patients with atrial fibrillation. Atrial fibrillation is the most common sustained arrhythmia encountered in clinical practice. The clinical usefulness of conventional Doppler indexes is limited in atrial fibrillation because of the altered left atrial pressure and loss of synchronized atrial contraction. Mitral inflow and mitral annulus velocities were measured simultaneously with tau in 27 patients with nonrheumatic atrial fibrillation at the cardiac catheterization laboratory. Among deceleration time of mitral inflow, peak mitral inflow velocity (E), and peak diastolic mitral annulus velocity (E), only E correlated with tau (r = 0.51, P =.007). Prolonged tau (>/=50 ms) could be predicted by E <8 cm/s with a sensitivity of 73% (16 of 22) and a specificity of 100% (5 of 5). The E/E ratio correlated with left ventricular filling pressure (r = 0.79, P <.001). The E/E ratio of >/=11 could predict elevated left ventricular filling pressure (>/=15 mm Hg) with a sensitivity of 75% (9 of 12) and a specificity of 93% (14 of 15). Mitral annulus velocity is useful in the detection of impaired left ventricular relaxation and estimation of filling pressure even in patients with atrial fibrillation.

Adult↗

Variant angina is not associated with angiotensin I converting enzyme gene polymorphism but rather with smoking.

BACKGROUND: Angiotensin converting enzyme (ACE) perhaps plays roles in regulating coronary vasomotor tone by producing angiotensin II and degrading bradykinin. OBJECTIVES: We sought to investigate the role of ACE gene polymorphism in the pathogenesis of variant angina and to compare it with that of other clinical risk factors for male patients with variant angina and age-matched and sex-matched control subjects. METHODS: We studied 78 male patients with variant angina who exhibited spontaneous or provoked coronary spasms during coronary angiography and compared prevalences of ACE gene genotype (deletion D and insertion I) and other risk factors between this group of patients with variant angina and age-matched and sex-matched control subjects whose angiograms were normal and in whom the ergonovine test did not cause spasms (n = 80). RESULTS: Smokers were more prevalent in the group of patients with variant angina (P < 0.05). Genotype and allele prevalences of the group of patients with variant angina (0.14, 0.53 and 0.33 for DD, DI and II and 0.41 and 0.59 for D and I, respectively) were no different from those of the control group (0.16, 0.49 and 0.35 for DD, DI and II and 0.40 and 0.60 for D and I). Multiple logistic regression analysis showed that smoking was a significant risk factor for variant angina (odds ratio 2.61, 95% confidence interval 1.03-6.66) whereas ACE genotype was not. CONCLUSIONS: Variant angina is associated with an environmental factor, such as smoking, rather than a genetic factor, such as ACE gene polymorphism.

Aged↗

Evidence of genetic progression in human gastric carcinomas with microsatellite instability.

Mutator phenotype tumors provide unique opportunities to unravel malignant progression because of various gene alterations acquired during clonal tumor evolution. Gastric carcinomas, which have been known to show frequent genetic instability, would be composed of initial gene alterations shared by most tumor areas and subsequent alterations restricted to particular tumor sites. To analyse the timing of genetic events, we examined separate sites of tumor tissue obtained from a given gastric carcinoma patient with microsatellite instability (MSI). Our study included 95 normal/tumor area pairs from 25 patients. Six of the 25 patients (24%) demonstrated various levels of MSI ranging from 7% (two of 30) to 97% (28 of 29) of markers tested in multiple tumor sites. Of the six patients, five manifested frameshift mutations in a tract of ten deoxyadenosines within transforming growth factor beta receptor type II and four demonstrated frameshift mutations in a tract of eight deoxyguanosines within BAX. These mutations were common to all tumor sites regardless of the various level of MSI phenotype, indicating initial events. Two of the six patients exhibited frameshift mutations in mononucleotide repeats of mismatch repair genes, hMSH3 and hMSH6, and the insulin-like growth factor II receptor in restricted tumor areas, indicating additional alterations. Insulin-like growth factor II receptor mutations appear to be caused by hMSH3 and hMSH6 mutations because the former mutations were confined to tumor portions with the latter two mismatch repair lesions. These results provide genetic progression evidence for gastric carcinomas of the mutator pathway. In this pathway, mismatch repair insufficiency initially targets mononucleotide tracts of transforming growth factor beta receptor type II and BAX. During tumorigenesis, primary mismatch repair failure may give rise to the secondary mismatch repair lesions, frameshift mutations of hMSH3 and hMSH6, which result in another tumorigenic mutation in the insulin-like growth factor II receptor.

Adult↗

Microsatellite instability-associated mutations associate preferentially with the intestinal type of primary gastric carcinomas in a high-risk population.

Most colon cancers exhibiting microsatellite instability (MI), a mutator phenotype of mismatch repair failure, are associated with mutations of the transforming growth factor-beta receptor type II genes (TGF-beta RII). Of intestinal- and diffuse-type gastric carcinomas, the former have been thought to arise from intestinal metaplasia in which gastric mucosa resembles intestinal mucosa. To evaluate the preferential histological type of MI-associated mutations in the development of gastric carcinoma, mutations of TGF-beta RII, p53, and p16 were analyzed for the two types of primary gastric carcinomas showing MI. Of 50 primary gastric carcinomas, including 33 intestinal types and 17 diffuse types, 15 cases (30%) demonstrated MI at 1 or more of the 11 microsatellite markers tested. The 15 MI cases were classified into two groups, widespread MI and low-level MI, based on the number of markers exhibiting the instability. Eleven were widespread MIs, and the remaining four cases were low-level MIs. Ten of the 11 (91%) widespread MIs were of the intestinal type, and 1 case (9%) was of the diffuse type. Of the 11 widespread MIs, 10 cases (91%) demonstrated frameshift mutations within the polyadenylate tract of the TGF-beta RII. The frameshift mutation was rarely detected at p53 and p16 (1 of 11, 9%). In contrast, the four low-level MI cases had no frameshift mutations within the repeat sequences of TGF-beta RII, p53, and p16, but two of the four cases demonstrated base substitution mutations within p53. Our results suggest that mismatch repair failure can mutate the TGF-beta RII and may provide one of the pathways for the development of the intestinal-type gastric carcinoma in high-risk populations.

Adenocarcinoma↗

Organization and characterization of the two yeast ribosomal protein YL19 genes.

A second copy of the Saccharomyces cerevisiae ribosomal protein YL19 gene was isolated through the use of the RPL19A gene as a probe. The nucleotide sequence of the gene, RPL19B, was determined. RPL19B contains an intron of 384 nucleotides located near its 5'-end. The coding regions of the two yeast genes, RPL19A and RPL19B, differ in only 34 nucleotides, none of which lead to changes in the amino-acid sequences of the predicted protein of 189 amino acids. RPL19B is also closely linked to a mitochondrial ADP/ATP carrier protein gene AAC2. Yeast cells containing disruption of either RPL19A or RPL19B formed smaller colonies than wild-type strains; however, simultaneous deletion of both genes is lethal.

Amino Acid Sequence↗

The N-terminal, dehydrogenase/cyclohydrolase domain of yeast cytoplasmic trifunctional C1-tetrahydrofolate synthase requires the C-terminal, synthetase domain for the catalytic activity in vitro.

The yeast ADE3(1-333) gene which encodes a truncated protein containing the N-terminal 5,10-methylene-tetrahydrofolate (THF) dehydrogenase (D)/5,10-methyl-THF cyclohydrolase (C) domain of cytoplasmic trifunctional C1-THF synthase is able to complement all the phenotypes associated with ade3 mutations in vivo. However, expression of the ADE3(1-333) gene in an ade3 strain does not retain any D activity in vitro. Expression in a yeast ade3 strain of the ADE3(1-333) fused to the Escherichia coli lacZ gene or to the yeast SER2 gene allows detection of D and C activities in vitro. These results indicate that the N-terminal D/C domain of C1-THF synthase requires the C-terminal 10-formyl-THF synthetase domain for stable catalytic activity in vitro.

Alleles↗