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Biomedical subjects

J K Park

Publications and source records attributed to J K Park.

At least 19 recordsLinked to original sources

Antisense oligonucleotides for ICAM-1 attenuate reperfusion injury and renal failure in the rat.

The leukocyte adhesion molecule ICAM-1 is implicated in ischemic renal reperfusion injury. We tested the utility of an ICAM-1 antisense oligodeoxyribonucleotide (ODN) with lipofectin, six hours prior to 30 minutes of bilateral renal ischemia in the rat. We measured ICAM-1 expression by immunohistochemistry and Western blot. Our antisense ODN showed a specific ICAM-1 surface expression inhibition in vitro. We then assessed ICAM-1 expression, leukocyte infiltration, serum creatinine, serum urea concentration, and renal histology in rats subjected to renal ischemia and controls. Serum creatinine and urea concentrations 12 and 24 hours post-ischemia were increased in saline treated and reverse ODN treated rats, compared to antisense ODN treated or sham operated rats (P < 0.05). Western blotting showed decreased ICAM-1 protein in antisense ODN-treated kidneys, compared to reverse ODN treated and saline treated ischemic controls (P < 0.05). Antisense ODN also ameliorated the ischemia-induced infiltration of granulocytes and macrophages (P < 0.05), and resulted in less cortical renal damage as assessed by a quantitative pathological grading scale (P < 0.05), compared to reverse ODN or saline treatment. Thus, antisense ODN for ICAM-1 protected the kidney against ischemic renal failure. The clinical applicability of these findings extends beyond ischemic acute renal failure.

Acute Kidney Injury

Conformational energies of substrates and inhibitors for carboxypeptidase A: stereoelectronic effect.

Because of the complexity involved in binding of a ligand to an enzyme the conformational preference of the bound ligand has not been well understood yet. We have examined the conformational energies of ligands for carboxypeptidase A using ab initio calculations. Considering the large stereoelectronic effect of 4-5 kcal/mol, the energetic preference of the unbound ligand conformers which arises from the stereoelectronic effect appears to play a significant role in determining the bound ligand conformations.

3-Mercaptopropionic Acid

Monocyte infiltration and c-fms expression in hearts of spontaneously hypertensive rats.

To elucidate mechanisms of myocardial hypertrophy in spontaneously hypertensive rats (SHR), we examined by Northern blotting the expression of the proto-oncogenes c-myc, c-fos, c-sis, and c-fms in the hearts of 4- and 14-week-old SHR and normotensive Wistar-Kyoto (WKY) rats. No difference in c-myc or c-fos expression could be found between SHR and WKY rats. In SHR, c-sis gave a weak and c-fms a very strong signal at 14 weeks, whereas no signal for these oncogenes was found in either WKY rats or Sprague-Dawley controls. Since c-fms codes for the receptor of monocyte colony-stimulating factor, we next used in situ hybridization to localize the presence of c-fms in hearts of SHR at 14 weeks. We found strong signals for c-fms around small blood vessels and between cardiac myocytes in 14-week-old SHR but none in WKY rats. Immunohistochemical staining corroborated the presence of clusters of monocyte infiltration at these same perivascular sites in significantly greater numbers in SHR than in WKY rats. We conclude that c-fms expression and macrophage infiltration are increased in the perivascular space of hypertrophied hearts from SHR. We suggest that mononuclear cell recruitment and induction of c-fms may play a role in the development of hypertension-associated myocardial hypertrophy.

Animals

Inhibition of acyl-CoA: cholesterol acyltransferase by isohalobacillin, a complex of novel cyclic acylpeptides produced by Bacillus sp. A1238.

A complex of metabolites consisting of two isomeric cyclic acylpeptides was isolated from a culture of Bacillus sp. A1238 by successive chromatographies on Amberlite XAD-7, silica gel and silica ODS columns. By a combination of spectroscopic and chemical analyses, the two subcomponents were identified as isomers of halobacillin, and the complex was designated isohalobacillin. Each molecule of isohalobacillin subcomponents contains either a 3-hydroxy-1-oxo-13-methyltetradecyl or a 3-hydroxy-1-oxo-12 methyltetradecyl moiety in place of a 3-hydroxy-1-oxopentadecyl moiety that is found in the halobacillin molecule. In a cell-free assay, isohalobacillin inhibited acyl-CoA: cholesterol acyltransferase by 50% at a concentration of 50 microM. When added to a culture of macrophage J774, the agent inhibited oxidized low density lipoprotein-induced synthesis of cholesteryl ester from [14C]oleate without affecting surface binding, internalization and degradation of the lipoprotein in the cells.

Amino Acid Sequence

Inhibition of the binding of oxidized low density lipoprotein to the macrophages by iturin C-related compounds.

Binding of modified lipoproteins including oxidized low density lipoprotein (oxidized LDL) to cell surface receptors is an initial step of conversion of monocyte-derived macrophages into lipid-laden foam cells, a key cellular component in the early lesions of atherosclerosis. We have searched for microbial metabolites that inhibit oxidized LDL-induced lipid accumulation in macrophages and isolated three compounds from a strain of Bacillus sp. as inhibitors of oxidized LDL binding. By chemical and spectroscopic analyses, these metabolites were shown to be related to the cyclic lipopeptide iturin C. Two of these compounds were novel metabolites having long chain beta-amino acid moieties of different length. These agents, at concentrations ranging from 5 to 20 microM, inhibited cell surface binding of oxidized 125I-LDL, resulting in reduced intracellular accumulation and degradation of the lipoprotein as well as in reduced cholesteryl ester formation from [14C]oleate in macrophages J774.

Amino Acid Sequence

Comparison of radiofrequency catheter ablation procedures in children, adolescents, and adults and the impact of accessory pathway location.

Radiofrequency (RF) catheter ablation is an accepted treatment for supraventricular tachycardia. However, the determinants of success, difficulty, or risk of complication associated with ablation have not been defined. This study evaluated patient age and location of the accessory or extranodal pathway as determinants of these procedural variables. Patients were stratified by age, with those aged 2 to 12 years classified as children, those aged 13 to 19 years as adolescents, and those > or = 20 years as adults. Locations were defined as right, septal, or left free wall accessory pathways, or extranodal slow pathways associated with atrioventricular node reentrant tachycardia. A total of 443 RF ablation procedures performed in 413 patients were evaluated. All procedures were performed in the same laboratory by the same group of physicians. Success rates for ablation of supraventricular tachycardia did not differ among the 3 age groups, ranging from 93% to 95%. Procedural aspects, including total procedure time, fluoroscopy time, and number of applications of RF energy also did not differ by age group. However, analysis of outcome and procedural complexity with respect to pathway location demonstrated that ablation of right free wall and septal accessory pathways was significantly more difficult than left free wall or slow pathway (success rates of 85% and 88% vs 97% and 98%, respectively, p = 0.01 and 0.02), irrespective of age. Additionally, right free wall pathways required significantly greater procedure time (mean = 5.1 hours), fluoroscopy time (mean = 78 minutes), and RF applications (median = 16) than ablations performed at other sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity: a preliminary report.

Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma (RCC) may be related to alterations in signal transduction pathways. We report that T cells from RCC patients have two alterations in kappa B motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of kappa B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro. On the basis of Western blotting experiments using antibodies to kappa B/Rel family proteins, the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 (p50) subunit. The second abnormality in kappa B-binding activity in T cells from these patients is that RelA, a member of the Rel homology family which is part of the normal NF-kappa B complex, was not induced in the nucleus following activation. Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells. The altered kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli.

Base Sequence

Atypical forms of supraventricular tachycardia due to atrioventricular node reentry in children after radiofrequency modification of slow pathway conduction.

OBJECTIVES: This study was performed to investigate the prevalence, mechanisms and clinical significance of supraventricular tachycardias inducible in children or adolescents after radiofrequency modification of slow pathway conduction for the treatment of atrioventricular (AV) node reentrant tachycardia. BACKGROUND: Limited data have been reported with regard to the physiology of AV node reentrant tachycardia in young patients. Radiofrequency catheter ablation allows evaluation of the effects of selective modification of the different pathways involved in AV node reentrant tachycardia. METHODS: Selective modification of slow pathway conduction was performed in 18 young patients (12.9 +/- 3.4 years old) with typical (anterograde slow-retrograde fast) AV node reentrant tachycardia. Radiofrequency energy was applied across the posteromedial or midseptal tricuspid annulus, guided by slow pathway potentials and anatomic position. Programmed stimulation was performed after modification of slow pathway conduction defined as noninducibility of typical AV node reentrant tachycardia. RESULTS: Modification of slow pathway conduction was achieved in each patient, with a median of four applications of radiofrequency energy. However, atypical forms of supraventricular tachycardia were inducible in 9 of 18 young patients after slow pathway modification: AV node reentrant tachycardia with 2 to 1 AV block (seven patients); anterograde fast-retrograde slow AV node reentrant tachycardia (five patients); and sustained accelerated junctional tachycardia (two patients). In comparison, atypical forms of tachycardia were inducible in only 2 of 59 adult patients with AV node reentrant tachycardia undergoing slow pathway modification in the same laboratory (p = 0.01). Additional applications of radiofrequency energy to the posteromedial tricuspid annulus rendered AV node reentrant tachycardia with 2 to 1 block and the fast-slow form of AV node reentrant tachycardia noninducible. Junctional tachycardia terminated spontaneously in both patients. During 9.8 +/- 3 months of follow-up, slow-fast AV node reentrant tachycardia has recurred in one patient, whereas fast-slow AV node reentrant tachycardia has occurred in two patients, both with inducible fast-slow tachycardia after the initial modification of slow pathway conduction. CONCLUSIONS: Initial applications of radiofrequency energy may selectively modify the anterograde conduction of slow pathway fibers in young patients with AV node reentrant tachycardia. This may result in AV node reentrant tachycardia with 2 to 1 AV block or a reversal of the reentrant circuit (fast-slow tachycardia). Induction of these tachyarrhythmias indicates that further applications of radiofrequency energy are required for the successful modification of slow pathway conduction in young patients. The increased prevalence of inducible atypical arrhythmias among young patients suggests differences in the anatomic or electrophysiologic substrate of AV node reentrant tachycardia that may evolve as a function of age.

Adolescent

Analysis of body surface area as a determinant of impedance during radiofrequency catheter ablation in adults and children.

Since most radiofrequency (RF) generators used for catheter ablation approximate a constant voltage output, applied power is inversely proportional to the impedance load of the system. Knowledge of the expected impedance load for a patient may facilitate selection of safer and more effective voltage output. Preliminary observations suggest that in adults, impedance is directly proportional to body surface area (BSA), thus prompting this study to determine whether this relation was maintained in smaller patients undergoing RF catheter ablation. Prospective analysis of impedance from 949 RF deliveries in 76 patients (BSA, 0.69-2.3 m2) revealed the mean impedance for all deliveries to be 103 +/- 8 ohms. Two-phase linear regression analysis revealed a significant, direct correlation between impedance and BSA in patients with a BSA > or = 1.5 m2 (P = .001); however, for patients with a BSA < 1.5 m2 there was no correlation. These results indicate that as patient size decreases below 1.5 m2, impedance is constant. Radiofrequency catheter ablation procedures in children may require selection of a voltage output similar to that used in adults in order to produce effective RF lesions.

Adult

Tumor necrosis factor alpha from peripheral blood mononuclear cells of IgA nephropathy and mesangial cell proliferation.

BACKGROUND: To investigate the role of mononuclear cells and their products on rat mesangial cell proliferation, we evaluated the effect of peripheral blood mononuclear cells (PBMC) culture supernatant of patients with IgA nephropathy on rat mesangial cells 3[H]-thymidine uptake, and measured the concentration of cytokines in the supernatant to find out which cytokine in PBMC culture supernatant has a major influence on mesangial cell 3[H]-thymidine uptake. METHODS: In ten patients with primary IgA nephropathy and 10 normal controls, PBMC were cultured with PHA (20 micrograms/ml) and con-A (10 micrograms/ml) for 24 hours, and supernatants were collected and stored at -70 degrees C until tested. Mesangial cell was cultured for 48 hours at a concentration of 10(4) cells/well with 1:2 or 1:10 diluted PBMC culture supernatant. 3[H]-thymidine uptake into rat mesangial cell was assayed after 18 hour culture. The cytokine concentrations of PBMC culture supernatant were measured by radioimmunoassay. RESULTS: When 1:2 diluted PBMC culture supernatant was added, the supernatant of IgA nephropathy induced higher 3[H]-thymidine uptake into mesangial cell compared with that of normal controls. 3[H]-thymidine uptake induced by 1:2 diluted PBMC culture supernatant was significantly higher than that induced by 1:10 diluted supernatant of IgA nephropathy. The concentration of TNF-alpha in PBMC culture supernatant of the patients with IgA nephropathy was higher than that of normal controls and showed a good correlation with the mesangial cell 3[H]-thymidine uptake. CONCLUSION: It is suggested that the mononuclear cell of IgA nephropathy may have the intrinsic property to produce more TNF-alpha which may be mitogenic to mesangial cells when stimulated with mitogens, and it may be related to the mesangial cell proliferation in IgA nephropathy.

Adolescent

Effect of angiotensin converting enzyme inhibitor on collagen production by cultured mesangial cells.

Cultured mesangial cells (MC) express renin mRNA and generate angiotensin I, supporting the action of local renin-angiotensin system. Also angiotensin II may act like a growth factor and was reported to increase collagen production (CP) in cultured MC. Angiotensin converting enzyme inhibitor is suggested to attenuate development and advancement of glomerulosclerosis, mainly with its hemodynamic effects. Therefore, we investigated the direct effects of enalapril (E) on CP by cultured MC. Rat MC were cultured in DMEM media alone, or containing high glucose (HG: 25 mM) or soluble immune complex (IC) prepared with bovine gamma globulin (BGG) and anti-BGG, with or without E (0.2 microgram/ml). CP was determined after 24 h by [3H] proline incorporation method. E significantly reduced CP by 43% in medium as compared with control (C) (C: 37,210 +/- 4,200 vs C + E: 21,350 +/- 5,080 cpm/well, p < 0.01). CP in medium increased in the presence of HG (123% of C) or IC (147% of C), which was, however, prevented with E (HG + E: 105% of C, IC + E: 116% of C). There were no differences of CP in cell layer between C (3,490 +/- 220 cpm/well) and C + E (3,340 +/- 190 cpm/well), and also no changes after addition of E in HG or IC groups. In conclusion, E directly attenuates CP by MC, even in the presence of HG or IC, independently of its hemodynamic effects.

Angiotensin-Converting Enzyme Inhibitors

The expression of beta 1 integrin and intercellular adhesion molecule-1 on mesangial cells and its modulation in glomerulonephritis.

OBJECTIVES: This study was performed to observe the effects of conditioned media (CM) of cultured mononuclear cells (MNC) on the expression of beta 1 integrin and intercellular adhesion molecule(ICAM)-1 on mesangial cells and the modulation by TGF-beta, TNF alpha, or hydroxyl radical Also these were examined in anti-Thy mesangial proliferative GN (MsPGN) or puromycin aminonucleoside nephrosis(PAN). METHODS: The expression of beta 1 integrin and ICAM-1 on mesangial cells was examined by ELISA and the modulation by TGF-beta, TNF alpha, or hydroxyl radical was investigated by using neutralizing antibody and dimethylthiourea. [.OH] scavenger. RESULTS: The CM of MNC from Control suppressed the beta 1 integrin expression and thymidine incorporation and increased ICAM-1 expression on mesangial cells, compared to media alone. Especially the significant increase in ICAM-1 expression was reversed by anti-TNF alpha antibody. beta 1 integrin expression on mesangial cells was higher by the addition of CM of MNC in MsPGN than in Control, which was prevented by anti-TGF beta antibody or dimethylthiourea. ICAM-1 expression was not different among groups. Thymidine incorporation by adding CM of MNC was lower in MsPGN and PAN, which was mitigated by anti-TGF beta and anti-TNF alpha. Thus the ratio of the expression of ICAM-1 to thymidine incorporation was higher in MsPGN and PAN. CONCLUSION: The expression of beta 1 integrin and ICAM-1, and the thymidine incorporation on mesangial cells are directly regulated by MNC, maybe through factors such as TGF beta or TNF alpha. In MsPGN, the overexpression of beta 1 integrin induced by MNC through TGF beta or hydroxyl radical on day 3 may be related to the pathogenesis.

Animals

Effects of positive acceleration on atrial natriuretic peptide in humans.

To study the effects of positive acceleration on the plasma atrial natriuretic peptide (ANP) and renin concentration (PRC), students of the Korean Air Force Academy and pilots were exposed to +6 Gz for 30 s in a human centrifuge without anti-G suits. An acceleration to +6 Gz caused a significant increase (p < 0.01) in the heart rate of both the student and pilot groups. We performed blood collection within 2 min after terminating centrifugation. Systolic blood pressure was increased significantly (p < 0.01), and heart rates were elevated and did not return to control levels by 2 min after centrifugation. Plasma ANP decreased significantly in both groups (p < 0.05). The difference in the percentage of ANP decrement was not significant between student and pilot groups. PRC increased significantly (p < 0.05) in both groups. This study demonstrated that high +Gz exposure in man caused a significant reduction of plasma ANP concentration, although PRC, heart rate, and blood pressure increase.

Acceleration