PubMed Health⌕ Search

Biomedical subjects

J U Lee

Publications and source records attributed to J U Lee.

At least 19 recordsLinked to original sources
PubMed1999

Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative, TAC-101, in human pancreatic-cancer cells.

In this study, we investigated the effect of a novel retinobenzoic acid, 4-[3,5-bis (trimethylsilyl) benzamido] benzoic acid (TAC-101), on the growth of 4 human pancreatic-cancer cell lines; BxPC-3, MIAPaCa-2, CFPAC-1 and AsPC-1. TAC-101 significantly inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells in a time- and concentration-dependent manner, but not the proliferation of AsPC-1 cells. Furthermore, the anti-proliferative effects of TAC-101 on BxPC-3 and MIAPaCa-2 cells were stronger than those of all-trans retinoic acid. Flow-cytometric analyses indicated that treatment of BxPC-3 with TAC-101 strongly induces cell-cycle arrest at the G1 phase. The cell-cycle arrest induced by TAC-101 was accompanied by reduction of retinoblastoma-gene product (RB) phosphorylation and an increase of 2 cyclin-dependent kinase (CDK) inhibitors, p21(WAF1/Cip1) (p21) and p27Kip1 (p27). TAC-101 also caused a decrease in cyclin A and thymidylate synthase, which are E2F-regulated gene products. No changes were observed in the expression of cyclin D1, cyclin E on CDK2. In addition, Hoechst staining, gel electrophoresis and flow-cytometric analysis indicated that a marked reduction in the number of BxPC-3 cells with TAC-101 was related to the induction of apoptosis. Our results suggest that TAC-101 inhibits the growth of certain pancreatic-cancer cells by means of G1-phase cell-cycle arrest resulting from the reduction of RB phosphorylation and the up-regulation of p21 and p27 as well as the induction of apoptosis. TAC-101 may therefore be a useful agent for new therapeutic strategies focusing on inhibition of pancreatic-cancer-cell proliferation.

Antineoplastic Agents↗
PubMed1999

Immunohistochemical analysis of Bcl-2, Bax, Bcl-X, and Mcl-1 expression in pancreatic cancers.

Expression of several members of the Bcl-2 family proteins was investigated by means of both immunohistochemical analysis in 30 invasive ductal adenocarcinomas and 23 intraductal papillary-mucinous tumors (IPMTs) and immunoblot analysis in 6 cancer tissues and 7 pancreatic cancer cell lines. We found that Bcl-2 was expressed in 23%, Bax in 53%, Bcl-X in 90%, and Mcl-1 in 90% of the invasive ductal adenocarcinomas. In intraductal papillary-mucinous adenocarcinomas, the expression rate of Bax was 44% and those of Bcl-XL and Mcl-1 were 88%; these values were higher than those for intraductal papillary-mucinous adenomas. Immunoblot analysis identified Bcl-XL as the predominant form of the Bcl-X protein in both pancreatic cancer tissues and cell lines, and demonstrated that both Bcl-XL and Mcl-1 protein levels were uniformly high in all cell lines. These results suggest that an imbalance between antiapoptosis proteins (such as Bcl-2, Bcl-XL, and Mcl-1) and proapoptotic proteins (such as Bax and Bcl-Xs) is involved in the distinctive biologic features of adenocarcinomas of the pancreas. Furthermore, predominantly high expressions of Bcl-XL and Mcl-1 in intraductal papillary-mucinous adenocarcinomas might be involved in the carcinogenesis in IPMT of the pancreas.

Adenocarcinoma↗
PubMed1999

Altered renal expression of nitric oxide synthase isozymes in spontaneously hypertensive rats.

OBJECTIVES: The present study was aimed at exploring whether the pathogenesis of hypertension is related with an altered expression of nitric oxide synthase (NOS) isozymes, i.e., bNOS, iNOS and ecNOS. METHOD: By Western blot analysis, the expression of NOS isozymes were determined in the kidney isolated from spontaneously hypertensive rats (SHR) and their normotensive control, Wistar-Kyoto rats (WKY). The NOx (nitrite/nitrate) contents were also determined in the kidney and plasma. RESULTS: The plasma NOx was significantly increased in SHR compared with that in WKY. The basal level of NOx was higher in the medulla and cortex of the kidney in SHR compared with that in WKY rat. bNOS proteins were expressed higher in the outer medulla and cortex, and iNOS proteins were higher in the inner medulla, outer medulla and cortex in SHR. ecNOS expression did not significantly differ between the SHR and WKY. CONCLUSIONS: These results indicate that the NO generation may not be impaired, but rather increased. It is likely that the increased expression of NOS isozymes is a counter-reactive phenomenon secondary to the increased blood pressure in this model of hypertension.

Animals↗
PubMed1999

Role of nitric oxide in the pathogenesis of diabetic nephropathy in streptozotocin-induced diabetic rats.

OBJECTIVES: Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. METHODS: To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2-/NO3-, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. RESULTS: Diabetic rats exhibited significantly elevated plasma and urinary NO2-/NO3- levels at 28 days after streptozotocin injection, and total excretion of NO2-/NO3- was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2-/NO3- concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. CONCLUSIONS: NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats exhibited enhanced renal hemodynamic responses to acute NO inhibition and excreted increased urinary NO2-/NO3-. These results suggest that excessive NO production may contribute to renal hyperfiltration and hyperperfusion in early diabetes.

Animals↗
PubMed1998

Involvement of matrix metalloproteinase-2 activity in invasion and metastasis of pancreatic carcinoma.

BACKGROUND: Activation of matrix metalloproteinase-2 (MMP-2) has been implicated in the progression, invasion, and metastasis of various cancers, but little information is available with regard to its role in pancreatic carcinoma with poor prognosis. METHODS: Gelatin zymography was used for the detection of latent and activated forms of MMP-2 and MMP-9 in 13 normal pancreatic tissue specimens, 14 chronic pancreatitis tissue specimens, and 33 pancreatic carcinoma tissue specimens. The gelatinase activity was quantified by densitometer, and the 66-kilodalton (kDa)/(66-kDa + 72-kDa) ratio was calculated as the MMP-2 activation ratio. Western blot analysis was performed to confirm the zymographic profile. RESULTS: Latent forms of MMP-2 and MMP-9 were detected in all samples of pancreatic carcinoma, chronic pancreatitis, and normal pancreatic tissue. The expression rate of the MMP-2 activated form in pancreatic carcinoma tissue specimens was 100% (33 of 33) but that of MMP-9 was 21%. The MMP-2 activation ratio in pancreatic carcinoma tissue specimens was significantly higher than that of chronic pancreatitis and normal pancreatic tissue specimens. The MMP-2 activation ratio in pT3 tumors was significantly higher than that in pT1 tumors. The MMP-2 activation ratio also was significantly higher in pancreatic carcinoma specimens with histologically positive regional lymph node metastasis and distant metastasis than those without metastasis. The MMP-2 activation ratio observed in patients who developed postresection recurrence within 6 months was significantly higher than that in patients without recurrence at 6 months. CONCLUSIONS: The results of the current study indicate that MMP-2 activation plays a significant role in tumor invasion and metastasis in pancreatic carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1998

The role of platelet-activating factor in regional myocardial ischemia-reperfusion injury.

BACKGROUND: This swine model was designed to elucidate the role of platelet-activating factor in regional myocardial ischemia-reperfusion injury. METHODS: In groups 1 and 2 (n = 12 each), the left anterior descending coronary artery was ligated for 60 minutes to induce regional myocardial ischemia followed by 6 hours of reperfusion. Group 1 received the platelet-activating factor antagonist TCV-309 before ischemia, whereas group 2 did not. Group 3 (n = 3) had a sham operation. RESULTS: Animals in group 2 exhibited significant (p < 0.05) hemodynamic instability and myocardial depression during the reperfusion period. Despite preventive measures, 7 of the 12 animals experienced severe dysrhythmias in the form of atrial and ventricular fibrillation leading to cardiac arrest. In contrast, animals in group 1 in whom the effects of platelet-activating factor were blocked by the specific platelet-activating factor receptor antagonist TCV-309 were hemodynamically stable and had significantly (p < 0.05) better myocardial function. This significant difference in global myocardial function between the groups was observed in the presence of similar morphologic findings and regional myocardial function. CONCLUSIONS: These results suggest that platelet-activating factor has a definite influence on global myocardial dysfunction associated with regional myocardial ischemia-reperfusion injury.

Animals↗
PubMed1998

Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis.

Tumour angiogenesis, as assayed by microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) have become established as important prognostic indicators for many tumour types. In this study, MVD and the expression of VEGF and PD-ECGF were examined by immunohistochemical staining of 50 pancreatic cancer tissues, and the relationships between either MVD or the expression of these two angiogenic factors and the clinicopathological features, including survival, were analysed. The expression of VEGF and PD-ECGF proteins were confirmed by Western blot analysis and VEGF mRNA isoforms were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in five pancreatic cancer cell lines. Twenty-eight (56%) of 50 pancreatic cancers were positive for VEGF protein in cancer cells, and 16 (32%) showed strong PD-ECGF staining in cancer and infiltrating cells. VEGF121 and VEGF165 were identified as the predominant species produced in pancreatic cancer cells. The overexpression of VEGF and PD-ECGF protein significantly correlated with high MVD (P = 0.002, 0.044, respectively). Advanced stage of disease was significantly more frequent in patients with high MVD (P = 0.025). No significant association was found between the expression of VEGF or PD-ECGF and clinicopathological features, except for tumour histology. The expression of PD-ECGF correlated with poor survival (P = 0.011), but MVD and VEGF expression were not found to be useful for the prediction of overall survival. This study suggests that VEGF and PD-ECGF may play an important role in tumour angiogenesis, and that PD-ECGF expression seems to be useful for establishing prognoses for pancreatic cancer.

Blotting, Western↗
PubMed1998

A human case of tick bite by Ixodes nipponensis.

A human case of the tick bite on the back of 36-year-old man was found in September 1995. On admission he complained of itching sensation and pain at the site. The removed tick was identified morphologically as Ixodes nipponensis.

Adult↗
PubMed1998

A case of arteriovenous type cardiac hemangioma.

Cardiac hemangiomas are rare primary tumors of the heart and constitute only 2.8% of primary cardiac tumors. They are classified into capillary, cavernous, epitheloid and arteriovenous type and the last one is the most uncommon type. We experienced a case of cardiac hemangioma which was diagnosed as arteriovenous type for the first time in Korea in the literature. The patient was a 54-year-old woman who presented with palpitation and anterior chest pain. The diagnosis was based upon coronary angiography which showed two tumor blushings located in the interatrial and interventricular septum with venous drainage to the coronary sinus and right atrium. Associated atrial fibrillation with rapid ventricular response was controlled with digitalis.

Atrial Fibrillation↗
PubMed1997

Detection of matrix metalloproteinase activity in human pancreatic cancer.

Destruction of the basement membrane (BM) is mandatory for tumor spread, and matrix metalloproteinases (MMPs) are known to be implicated in colon cancer invasion and metastasis by digesting type IV collagen, a main component of the BM. The current study analyzed the expression of MMP-2 and MMP-9 in pancreatic cancer tissues. Frozen specimens of pancreatic cancer (n = 10), a liver metastatic nodule from pancreatic cancer (n = 1), and normal pancreas (n = 3) were homogenized and analyzed by zymography. The activated form of MMP-9 (82 kDa) was detected in all of the normal and malignant tissues, while the activated form of MMP-2 (62 kDa) was detected in all of the pancreatic cancers and its metastatic tissue, but not in the normal pancreatic tissues. These results indicate that expression of the activated form of MMP-2 may be specific to pancreatic cancer, while that of MMP-9 may be unrelated to it.

Biomarkers, Tumor↗
PubMed1997

Effects of structural modulation on biological activity of bombesin analogues with (E)-alkene bond.

The specific bombesin receptor antagonist, (E)-alkene bombesin isostere (EABI-1), [D-Phe6,Leu13psi[(E)CH=CH]Leu14]bombesin(6-14) is a potent antagonist in terms of inhibition of bombesin-stimulated amylase release from rat pancreatic acini. This study examined the effects of EABI-1 (L-L diastereomer) and three novel bombesin analogues on amylase release in rat pancreatic acini. EABI-2 is a L-D diastereomer of EABI-1. EABI-3 is an analogue, of which leucine at position 13 of EABI-1 was replaced with valine. EABI-4 is a L-D diastereomer of EABI-3 (L-L). The order of agonist potency was EABI-2>EABI-3>EABI-4. EABI-1 showed no agonist activity at concentrations up to 100nM. On the other hand, all of four analogues had antagonist activity. The order of antagonist potency was EABI-1>EABI-3>EABI-4>EABI-2. EABI-1 was a complete antagonist, EABI-2 and EABI-3 were partial agonists, and EABI-4 had a weak agonist effect. The present study provides a useful information on the future development of peptide analogues for anticancer agents and biological tools for investigating actions of bombesin family peptides.

Amylases↗
PubMed1997

Role of apoptosis in duct obstruction-induced pancreatic involution in rats.

It has been recognized in mammals that after pancreatic duct obstruction, acinar cells progressively disappear and pancreatic islets are preserved. Previous studies by electron microscopy have suggested the involvement of apoptosis in acinar cell deletion. In the present study, we employed molecular biological methods and investigated whether acinar cell deletion is due to apoptosis. In male Sprague-Dawley rats, pancreatic duct ligation was performed through a left paramedian incision. Pancreatic tissue was studied at each of the following intervals after ligation: 3, 6, 12, 18, and 24 h and 2, 3, 5, and 7 days. DNA fragmentation was determined by in situ labeling of DNA strand breaks on tissue sections [fluorescein-labeled terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method (TUNEL)] and by electrophoretic detection of the fragments of extracted DNA. Tissue sections were also examined by hematoxylin/eosin staining and immunohistochemical staining of insulin. Pancreatic duct ligation induced acinar cell deletion by day 5. Pancreatic tissue from control rats demonstrated no TUNEL-positive nuclei. In contrast, acinar cells from rats 12 h to 5 days after duct ligation showed TUNEL-positive nuclei. The number of TUNEL-positive nuclei was maximum 2 days after duct ligation. Electrophoresis showed DNA fragmentation after duct ligation. Control rats showed a genomic DNA pattern. Islets were preserved throughout the experimental period in duct-ligated rats and control rats. The results suggest that apoptosis may be the dominant form of acinar cell death in the rat pancreatic duct ligation model.

Amylases↗
PubMed1997

Expression of Bcl-2 and PCNA in duct cells after pancreatic duct ligation in rats.

Obstruction of the pancreatic duct induces acinar cell deletion followed by duct proliferation and interstitial fibrosis. Apoptosis has been reported to be involved in the induction of acinar cell deletion after pancreatic duct ligation (PDL) in rats, however, the mechanism of pancreatic duct cell proliferation is still unknown. We hypothesized that Bcl-2 (antiapoptosis protein) and PCNA (cell cycle-related protein) could be involved in the mechanism of pancreatic duct cell proliferation after PDL. In PDL, rats, acinar cells decreased in number and disappeared completely after duct ligation and duct-lining cells increased in number and formed duct-tubular complexes. Immunohistochemical study showed that PCNA expression appeared in the ductules and centroacinar cells from early stages after duct ligation and that Bcl-2 expression in duct cells, which was faint in normal pancreas, increased significantly when acinar cells were diminishing. Western blotting demonstrated that Bcl-2 was detected as a single band at 26 kDa, and the intensity of Bcl-2 in PDL rats was approximately ninefold stronger than in normal pancreas. Expression of Bcl-2 and PCNA after pancreatic duct ligation may be related to the prevention of apoptosis and cell proliferation of pancreatic duct cells in rats.

Animals↗
PubMed1997

Role of neutrophils in cerulein-induced pancreatitis in rats: possible involvement of apoptosis.

We investigated the role of neutrophils and the involvement of apoptosis in cerulein-induced acute pancreatitis. Male Sprague-Dawley rats were divided into 2 groups. In the control group, acute pancreatitis was induced by subcutaneous injections of cerulein. In methotrexate-treated group, the rats received intraperitoneal injections of methotrexate to produce neutrophil depletion before the injections of cerulein. The rats were sacrificed at the indicated time points until 72 h after the first injection of cerulein. Neutrophil depletion ameliorated pancreatic edema and vacuole formation in acinar cells during the early stages of cerulein-induced acute pancreatitis. Electron microscopy, DNA gel electrophoresis and in situ nick end-labeling revealed the involvement of apoptosis in acinar cells in cerulein-induced acute pancreatitis. Furthermore, the number of apoptotic acinar cells in neutrophil-depleted rats showed an about 2-fold increase during the late stages when compared with those in the control rats. Our results suggest that neutrophil depletion in cerulein-induced pancreatitis leads to amelioration of pancreatic injury during the early stage, and enhancement of apoptosis by neutrophil depletion occurs during the late stage.

Acute Disease↗
PubMed1997

Effects of altered body fluid balance and high blood pressure on the plasma brain natriuretic peptide in rats.

The present study was aimed to investigate the regulatory mechanisms of BNP release. Effects of acute and chronic perturbations in body fluid balance, changes in BP, and regulatory roles of NO and endothelin systems on BNP release were examined in rats. Although acute extracellular volume expansion did not have significant effects on plasma BNP, prolonged high-salt intake increased plasma BNP levels. Plasma BNP levels were also higher in 2K1C rats compared with the control. Although infusion of L-NAME increased the plasma BNP in control, it did not further affect the plasma BNP in rats with high-salt intake. Although L-arginine (20 mg.kg-1 per min) per se did not have significant effects on plasma BNP, it blocked the stimulatory effect of L-NAME (200 micrograms.kg-1 per min). Plasma BNP was severalfold increased following a single injection of endothelin (0.3 micrograms/kg) in normal and high-salt intake groups, the magnitude of which was not significantly affected by the high-salt intake. Although indomethacin did not have significant effects on plasma BNP in normal rats, it blocked the stimulatory effect of 2K1C hypertension. It is concluded that BNP is regulated by chronic changes in body fluid balance and blood pressure. It is also suggested that endothelin and NO systems may directly regulate the secretion of BNP in vivo. An endogenous prostaglandin synthesis may be involved in the stimulated release of BNP in hypertension.

Animals↗
PubMed1997

Attenuated central pressor response to nitric oxide synthesis inhibition in chronic renal failure rats.

OBJECTIVES: Central and peripheral roles of nitric oxide (NO) in blood pressure regulation have been suggested. The present study was aimed at examining if the role of NO in blood pressure regulation is altered in chronic renal failure. METHODS: Blood pressure responses to acute inhibition of NO were examined in 5/6 nephrectomized rats. Three weeks after the renal ablation, under thiopental (50 mg/kg, i.p.) anesthesia, an intracerebroventricular cannula was placed in the left lateral ventricle and the femoral vein was cannulated to serve as an infusion route. The arterial blood pressure was measured in the right femoral artery. NG-nito-L-arginine methyl ester (L-NAME) was infused (100 microgram/kg per min for 60 min either intracerebroventricularly or intravenously. RESULTS: Chronic renal failure rats showed a significantly higher arterial pressure than the control rats (147 +/- 14 mmHg vs. 122 +/- 13 mmHg). Intracerebroventricular L-NAME did not affect the arterial pressure in chronic renal failure rats (0.5 +/- 4 mmHg increase from the basal), while it significantly increased the arterial pressure in normal rats (22 +/- 3 mmHg increases from the basal). Intravenous L-NAME increased the arterial pressure, the magnitude of which did not differ between the normal and chronic renal failure rats (24 +/- 3 vs. 16 +/- 3 mmHg increases from the basal). CONCLUSION: These results indicate that the central role of NO in the regulation of blood pressure is altered in chronic renal failure.

Analysis of Variance↗
PubMed1997

Changes of the plasma endothelin in adaptation to increased salt intake in rats.

OBJECTIVES: Roles for vascular endothelial hormones in body fluid balance have been variously suggested. The present study was aimed at investigating whether the plasma endothelin is altered in responses to acute and chronic perturbations in body fluid balance. METHODS: Effects of intravenous infusion of MG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of endothelium-derived nitric oxide (NO) synthesis, on urinary excretion, blood pressure and plasma levels of endothelin were examined in rats kept on either normal or high-salt diet for two weeks. The plasma endothelin levels in response to an acute extracellular volume expansion (VE) were also determined in normal and 2-kidney, 1 clip (2K1C) hypertensive rats. RESULTS: L-NAME (20 and 200 micrograms.kg(-1) per min) elicited diuretic and natriuretic effects in association with increased blood pressure both in normal and high-salt rats. In high-salt rats, however, the urinary response to L-NAME was attenuated and the pressor response was augmented compared with the control. High-salt intake per se caused a small, but significant, increase of the plasma endothelin. L-NAME (200 micrograms(-1) per min) markedly increased the plasma endothelin was also marginally increased following VE, the magnitude of which did not differ between the normal and 2K1C rats. CONCLUSION: These results suggest that the endothelin system takes part in adaptation to increased salt-intake. Another evidence indicating a negative modulation of NO on the release of endothelin is also provided.

Adaptation, Physiological↗