Biomedical subjects

Young Joo Lee

Publications and source records attributed to Young Joo Lee.

At least 19 recordsLinked to original sources

PubMed2006

Glycogen synthase kinase-3beta activity plays very important roles in determining the fate of oxidative stress-inflicted neuronal cells.

Glycogen synthase kinase-3, especially the beta form (GSK-3beta), plays key roles in oxidative stress-induced neuronal cell death, an important pathogenic mechanism of various neurodegenerative diseases. Although the neuroprotective effects of GSK-3beta inhibitors have been described, the optimal level of GSK-3beta inhibition for neuronal cell survival has not yet been determined. We investigated the effect of varying GSK-3beta activity on the viability of oxidative stress-injured neuronally differentiated PC12 (nPC12) cells and intracellular signals related with the GSK-3beta and caspase-3 pathways. Compared to the nPC12 control cells treated with only 100 microM H(2)O(2), treatment of 50-200 nM GSK-3beta inhibitor II or 25-500 nM GSK-3beta inhibitor VIII reduced the increased enzyme activity by about 50% and protected the cells against H(2)O(2)-induced oxidative stress. The optimal concentration of GSK-3beta inhibitor II enhanced heat shock transcription factor-1 levels, decreased levels of phosphorylated tau (Ser202) and cytosolic cytochrome c, activated caspase-3, and cleaved poly (ADP-ribose) polymerase. In contrast, higher concentrations of GSK-3beta inhibitor II (more than 500 nM) induced neuronal cell death and showed opposite effects relative to the above described intracellular signals. These results suggest that optimized inhibitor levels for modulating GSK-3beta activity may prevent apoptosis induced by oxidative stress associated with neurodegenerative diseases.

Animals↗

PubMed2006

Calbindin-D9k mRNA expression in the rat uterus following exposure to methoxychlor: a comparison of oral and subcutaneous exposure.

Calbindin-D(9k) (CaBP-9k) is a cytosolic calcium-binding protein that is induced by estrogenic compounds possibly through estrogen receptors. We compared CaBP-9k mRNA expression in the uterus with uterotrophic response in immature rats exposed to methoxychlor (MC), an environmental chemical with estrogenic activity. MC was orally or subcutaneously administered to 3-week-old female Sprague-Dawley rats for 3 days. The weights of the uterus and vagina significantly increased in the oral treatment group at a dose of 50, 100 and 200 mg/kg, but those of the subcutaneous (SC) treatment group only increased at 200 mg/kg. Northern blot analysis showed that CaBP-9k mRNA expression was significantly induced in a dose-dependent manner at doses of 50, 100 and 200 mg/kg/day in the oral treatment group. SC administration of MC induced significant expression at only a dose of 200 mg/kg/day; this was similar to the uterotrophic response. MC has an estrogenic effect on the uterus as shown by the increase in weight and induction of CaBP-9k mRNA expression, which were much greater following exposure via oral gavage than via the SC route. The strong correlation between the results of in vivo uterotrophic assay and CaBP-9k mRNA expression suggests that CaBP-9k mRNA expression in the rat uterus may be used as an early gene marker for detection of the estrogenic effects of putative environmental chemicals.

Administration, Oral↗

PubMed2006

Hypoxic activation of unoccupied estrogen-receptor-alpha is mediated by hypoxia-inducible factor-1 alpha.

The estrogen receptor (ER) plays an important role in breast cancer development and progression. Hypoxia has been shown to modulate the level of ERalpha expression, which is intimately associated with the biology of breast carcinomas. However, the effect of hypoxia on ERalpha-mediated transactivation is largely unknown. In this report, we have examined ligand-independent transcriptional activation of ERalpha by hypoxia. The hypoxia-induced ERalpha-mediated transcriptional response was inhibited by the ER antagonist ICI 182,780 as determined by transient expression of ERalpha and ER-responsive reporter plasmids in the HEK 293 cells. Hypoxic activation of ERalpha was dependent on the increased expression of hypoxia-inducible factor-1alpha (HIF-1alpha), as examined in HEK 293 cells under conditions of normoxia. These results indicate that hypoxia activates ERalpha in a ligand-independent manner, possibly through the interaction between HIF-1alpha and ERalpha.

Cell Hypoxia↗

PubMed2006

Hydrogel behavior of a sugar-based gelator by introduction of an unsaturated moiety as a hydrophobic group.

The new sugar-based gelators 1 and 2 were synthesized, and their gelation abilities were evaluated in organic solvents and in water. Compound 1 gelates both water and organic solvents whereas 2 gelates only organic solvents. Superstructural difference between hydrogel 1 and organogel 2 was investigated by CD, TEM, AFM, 1H NMR and XRD. Hydrogel 1 displays a well-developed helical ribbon structure with 20-150 nm diameter and a length of several hundred microm whereas organogel 2 shows a twisted fiber structure of diameter 20 nm. CD measurements of hydrogel 1 and organogel 2 indicate that hydrogel 1 maintains a well-ordered chiral structure whereas organogel 2 maintains a relatively disordered chiral structure. The 1H NMR and XRD results suggest that the hydrophobic interaction in hydrogel 1 are relatively weak, with a relatively small region interdigitated between lipophilic alkyl groups. In addition, upon irradiation at 254 nm wavelength, hydrogel 1 reveals a red coloration at 540 nm. These results indicate that the self-assembled hydrogel 1 was polymerized by UV-irradiation. The intensity of the CD spectrum of the polymerized hydrogel markedly decreased. This result indicates that upon polymerization the highly ordered chiral structure of hydrogel 1 changes to a disordered molecular packing structure.

Journal Article↗

PubMed2006

The role of matrix metalloproteinase 9 in early neurological worsening of acute lacunar infarction.

The involvement of matrix metalloproteinases (MMPs) in ischemic-stroke-induced inflammatory response has recently been suggested; however, the relationship between MMPs and stroke progression has not been evaluated. We investigated the role of MMPs in neurological worsening of acute lacunar infarction. Forty-nine consecutive patients with an acute lacunar infarction (as defined by clinical and MRI criteria within 48 h after stroke onset) were evaluated. Clinical, biochemical, rheological, inflammatory and other parameters were compared between progressive and nonprogressive groups. Among the variables, only inflammatory parameters, including MMP-9 and erythrocyte sedimentation rate, were associated with neurological worsening of acute lacunar infarction (p<0.05). These results suggest that the inflammatory process could play an important role in early neurological worsening of acute lacunar infarction.

Acute Disease↗

PubMed2006

The effect of luteolin-7-O-beta-D-glucuronopyranoside on gastritis and esophagitis in rats.

This study evaluated the inhibitory action of luteolin-7-O-beta-D-glucuronopyranoside, luteolin which was isolated from Salix gilgiana leaves, and omeprazole on reflux esophagitis and gastritis in rats. Reflux esophagitis and gastritis were induced surgically and by the administration of indomethacin, respectively. The intraduodenal administration of luteolin-7-O-beta-D-glucuronopyranoside decreased the ulcer index, injury area, gastric volume and acid output, and increased the gastric pH compared with luteolin. Luteolin-7-O-beta-D-glucuronopyranoside significantly decreased the size of the gastric lesions that had been induced by exposing the gastric mucosa to indomethacin. The malondialdehyde content, which is the end product of lipid peroxidation, was increased significantly after inducing of reflux esophagitis. The malondialdehyde content was decreased by Luteolin-7-O-beta-D-glucuronopyranoside but not luteolin or omeprazole. Luteolin-7-O-beta-D-glucuronopyranoside has a more potent antioxidative effect than luteolin. Luteolin-7-O-beta-D-glucuronopyranoside is a promising drug for the treatment of reflux esophagitis and gastritis.

Animals↗

PubMed2005

The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice.

Epigallocatechin gallate (EGCG) is a constituent of green tea, and increasing evidence suggests that EGCG has neuroprotective effects on oxidative stress-injured neuronal cells, especially motoneurons. Although the neuroprotective effects of EGCG have been demonstrated in Parkinson's and Alzheimer's diseases and ischemic stroke models, there has been no report on the effect of EGCG on an in vivo model of amyotrophic lateral sclerosis (ALS). This study was undertaken to evaluate the effect of EGCG on ALS model mice with the human G93A mutated Cu/Zn-superoxide dismutase (SOD1) gene. We treated each group of 11 ALS model mice with EGCG (1.5, 2.9, and 5.8 microg/g body weight), dissolved in 0.5 ml of 0.9% sterile NaCl, and one group of 11 with 0.5 ml of 0.9% sterile NaCl (control group) intraorally every day after 60 days of age (presymptomatic treatment). The treatment of more than 2.9 microg EGCG/g body weight significantly prolonged the symptom onset and life span, preserved more survival signals, and attenuated death signals. These data suggest that EGCG could be a potential therapeutic candidate for ALS as a disease-modifying agent.

Amyotrophic Lateral Sclerosis↗

PubMed2005

Hypertonic sodium chloride induction of cyclooxygenase-2 occurs independently of NF-kappaB and is inhibited by the glucocorticoid receptor in A549 cells.

Cellular response to a hypertonic environment is important for fluid clearance in the lung. Hypertonicity modulates prostaglandin synthesis by influencing cyclooxygenase-2 (COX-2) expression in tissues such as liver and kidney via a mitogen-activated protein kinase (MAPK)-dependent pathway. However, little is known about COX-2 expression in response to hypertonicity in the lung. COX-2 mRNA accumulation induced by hypertonic NaCl was detected after 1 h of treatment, and COX-2 mRNA continued to accumulate until 18 h, the longest time point examined, in human alveolar epithelial A549 cells. This induction was a transcriptional event that occurred in the absence of the protein synthesis inhibitor cycloheximide and was the result of enhanced promoter activity, as examined with the use of full-length COX-2 promoter-driven reporter plasmids. The induction of COX-2 expression by hypertonic NaCl did not require the activation of NF-kappaB. The p38 MAPK inhibitor, SB203580, or MEK1/2 inhibitor, U0126, inhibited hypertonic induction of COX-2 expression. We examined whether the hypertonic induction of COX-2 was under the influence of glucocorticoid; we found that COX-2 promoter activity and mRNA and protein levels were depressed by dexamethasone and antagonized by the glucocorticoid receptor (GR) antagonist RU486. Our data demonstrate that the induction of COX-2 expression by hypertonic NaCl occurs independently of NF-kappaB and is inhibited by the GR in A549 cells.

Base Sequence↗

PubMed2005

Two-cation competition in ionic-liquid-modified electrolytes for lithium ion batteries.

It is a common observation that when ionic liquids are added to electrolytes the performances of lithium ion cells become poor, while the thermal safeties of the electrolytes might be improved. In this study, this behavior is investigated based on the kinetics of ionic diffusion. As a model ionic liquid, we chose butyldimethylimidazolium hexafluorophosphate (BDMIPF(6)). The common solvent was propylene carbonate (PC), and lithium hexafluorophosphate (LiPF(6)) was selected as the lithium conducting salt. Ionic diffusion coefficients are estimated by using a pulsed field gradient NMR technique. From a basic study on the model electrolytes (BDMIPF(6) in PC, LiPF(6) in PC, and BDMIPF(6) + LiPF(6) in PC), it was found that the BDMI(+) from BDMIPF(6) shows larger diffusion coefficients than the Li(+) from LiPF(6). However, the anionic (PF(6)(-)) diffusion coefficients present little difference between the model electrolytes. The higher diffusion coefficient of BDMI(+) than that of Li(+) suggests that the poor C-rate performance of lithium ion cells containing ionic liquids as an electrolyte component can be attributed to the two-cation competition between Li(+) and BDMI(+).

Journal Article↗

PubMed2005

Differential effects of diallyl disulfide on neuronal cells depend on its concentration.

Diallyl disulfide (DADS) is one of the organosulfur compounds of garlic. The effects of DADS on neuronal cells have not clearly been established. We investigated its effects on the viability of neuronal cells (N18D3 cells), the levels of free radical and membrane lipid peroxidation, and the cell signals, such as phosphatidylinositol 3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3). When N18D3 cells were treated with several concentrations of DADS, the viability was not affected up to 25 microM, however, decreased at higher than 25 microM. The levels of free radicals and membrane lipid peroxidation were increased in a dose-dependent manner, especially at higher than 25 microM. The treatment of N18D3 cells with 25 microM DADS slightly increased the expressions of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3, but the treatment with 100 microM significantly reduced them. To evaluate whether low concentration of DADS, up to 25 microM, had protective effect on oxidative stress-injured N18D3 cells, the viability of N18D3 cells (pretreated with DADS for 2h versus not pretreated) was evaluated 24h after their exposure to 100 microM H(2)O(2) for 30 min. Compared to the cells treated with only 100 microM H(2)O(2), the pretreatment with 25 microM DADS increased the viability, and the expressions of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3. These results indicate that low concentration of DADS has protective effects on N18D3 cells, whereas high concentration is rather cytotoxic. Therefore, some specific optimum concentration of DADS may be a new potential therapeutic strategy for oxidative stress-injury in vitro model of neurodegenerative diseases.

Allyl Compounds↗

PubMed2005

Multicenter analysis of clinicopathologic features of intraductal papillary mucinous tumor of the pancreas: is it possible to predict the malignancy before surgery?

BACKGROUND: Despite recently increasing numbers of reports on intraductal papillary mucinous tumors (IPMTs), difficulties still remain in terms of diagnosis, treatment, and prognosis. The purpose of this multicenter study was to evaluate the clinicopathologic features of IPMT in Korea and to suggest predictive criteria for malignancy in IPMT. METHODS: We retrospectively reviewed the clinicopathologic data of 208 patients who underwent operations for IPMT between 1993 and 2002 at 28 institutes in Korea. RESULTS: Of the 208 patients (mean age, 61 years), 147 were men and 61 were women. A total of 124 patients underwent pancreatoduodenectomy, 42 underwent distal pancreatectomy, 17 underwent total pancreatectomy, and 25 underwent limited pancreatic resection. There were 128 benign cases (adenoma, n = 62; borderline, n = 66) and 80 malignant cases (noninvasive, n = 29; invasive, n = 51). A significant difference in 5-year survival was observed between the benign and malignant groups (92.6% vs. 65.3%; P = .006). Of the six factors (age, location, duct dilatation, mural nodule, main duct type, and tumor size) that showed statistical differences by univariate analysis between the benign and malignant groups, three were significant by multivariate analysis--namely, mural nodule (P = .009), tumor size (P = .023), and a dilated duct size (P = .010). CONCLUSIONS: A significant proportion of IPMTs are malignant, although the overall prognosis of IPMT is superior to that of ordinary pancreatic cancer. Radical surgery is recommended for IPMT with the predictors of malignancy: mural nodule, tumor size (> or =30 mm), and dilated duct size (> or =12 mm).

Adenocarcinoma, Mucinous↗

PubMed2005

Two-dimensional gel analysis of protein expression profile in squamous cervical cancer patients.

OBJECTIVES: Screening in cervical cancer is progressing to find out candidate genes and proteins, which may work as biological markers and play a role in tumor progression. We examined the protein expression patterns of squamous cell carcinoma (SCC) tissues from Korean women using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of fight (MALDI-TOF) mass spectrometer. METHODS: Normal cervix and SCC tissues were solubilized and 2-DE was performed using the pH 3-10 linear IPG strips of 17 cm length and silver stained. Protein expression was evaluated using PDQuest 2-D software. The differentially expressed protein spots were identified with MALDI-TOF mass spectrometer and the peptide mass spectra identification was performed using Mascot program searching the Swiss-prot or NCBInr databases. RESULTS: A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins were down-regulated. Among the proteins identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase, apolipoprotein a1) were previously known proteins involved in tumor and 21 proteins were newly identified in this study. CONCLUSIONS: 2-DE offers total protein expression profiles of SCC tissues and further characterization of proteins that are differentially expressed will give a chance to identify tumor-specific diagnostic markers for SCC.

Adult↗

PubMed2005

Role of GSK-3beta activity in motor neuronal cell death induced by G93A or A4V mutant hSOD1 gene.

Point mutations such as G93A and A4V in the human Cu/Zn-superoxide dismutase gene (hSOD1) cause familial amyotrophic lateral sclerosis (fALS). In spite of several theories to explain the pathogenic mechanisms, the mechanism remains largely unclear. Increased activity of glycogen synthase kinase-3 (GSK-3) has recently been emphasized as an important pathogenic mechanism of neurodegenerative diseases, including Alzheimer's disease and ALS. To investigate the effects of G93A or A4V mutations on the phosphatidylinositol-3-kinase (PI3-K)/Akt and GSK-3 pathway as well as the caspase-3 pathway, VSC4.1 motoneuron cells were transfected with G93A- or A4V-mutant types of hSOD1 (G93A and A4V cells, respectively) and, 24 h after neuronal differentiation, their viability and intracellular signals, including PI3-K/Akt, GSK-3, heat shock transcription factor-1 (HSTF-1), cytochrome c, caspase-3 and poly(ADP-ribose) polymerase (PARP), were compared with those of wild type (wild cells). Furthermore, to elucidate the role of the GSK-3beta-mediated cell death mechanism, alterations of viability and intracellular signals in those mutant motoneurons were investigated after treating the cells with GSK-3beta inhibitor. Compared with wild cells, viability was greatly reduced in the G93A and A4V cells. However, the treatment of G93A and A4V cells with GSK-3beta inhibitor increased their viability by activating HSTF-1 and by reducing cytochrome c release, caspase-3 activation and PARP cleavage. However, the treatment did not affect the expression of PI3-K/Akt and GSK-3beta. These results suggest that the G93A or A4V mutations inhibit PI3-K/Akt and activate GSK-3beta and caspase-3, thus becoming vulnerable to oxidative stress, and that the GSK-3beta-mediated cell death mechanism is important in G93A and A4V cell death.

Alanine↗

PubMed2005

Long-term growth of pediatric patients following living-donor liver transplantation.

In order to determine the influence of living donor liver transplantation (LDLT) on long-term growth, we studied the progress of 36 children who had survived more than 5 yr after LDLT from 1994 to 1999. The median age at the transplantation was 1.5 yr (range: 6 months-15 yr) and the median follow-up period was 6.5 yr (range: 5-9 yr). A height standard deviation score (zH) was analyzed for each patient according to medical records. Significant catch-up growth occurred within 2 yr after LDLT with a mean zH changing from -1.2 to 0.0 and was maintained for up to 7 yr post-transplantation (zH-0.1). Younger children (<2 yr) were more growth-retarded at the time of LDLT, but showed higher catch-up growth rates and their final zH was greater than that of older children. Children with liver cirrhosis were more growth-retarded at the time of LDLT, but showed significant catch-up growth and their final height was similar to children with fulminant hepatitis. Growth in children who experienced significant hepatic dysfunction after LDLT was not significantly different from those without graft dysfunction. There was no difference between the types of immunosuppressants used. Our finding suggests that LDLT can result in adequate catchup linear growth, and this effect can persist even after 7 yr post-transplantation.

Adolescent↗

PubMed2005

[Preoperative diagnosis and management for hilar cholangiocarcinoma].

Liver resection with extrahepatic bile duct resection, wide lymph node dissection and caudate lobectomy has become the standard treatment for patients with hilar cholangiocarcinoma. More extended surgery, such as hepatopancreatoduodenectomy, combined portal vein and liver resection, has been accepted for treatment. Such aggressive resection could only offers better chance of long-term survival, but postoperative morbidity and mortality is still high. Various preoperative diagnostic and management modalities including PTBD, PTCS, angiography, MR angiography, MR cholangiography, DCT, CT angiography and PTPE are very important for optimal treatment and reduced mortality. It is recommended that surgeons, physicians, endoscopists, and radiologists, including interventional radiologists should perform the diagnosis and preoperative management of patients with hilar cholangiocarcinoma in a concerted way.

Bile Duct Neoplasms↗

PubMed2004

Extracts from Schizandra chinensis fruit activate estrogen receptors: a possible clue to its effects on nitric oxide-mediated vasorelaxation.

Schizandra chinensis fruit has long been used for the treatment of cardiovascular symptoms associated especially with menopausal symptoms in Korea. To provide a scientific rationale for such uses, we have investigated the vasorelaxant effects of Schizandra chinensis fruit on the vasomotor tone of the rat thoracic aorta in an organ bath. The crude extracts of Schizandra chinensis fruit (SC-Ex) elicited a transient relaxing response in the endothelium-intact rat aorta contracted with norepinephrine. This relaxant effect was abolished by removal of the endothelium, and also by pretreatment with nitric oxide synthase inhibitor. We then examined whether this vasodilatory effect occurs through estrogen receptor by reporter assays. SC-Ex activated the estrogen-responsive luciferase gene in COS cells transiently transfected with estrogen receptor and reporter plasmids. The activation was maintained in the butanol-soluble fraction and further increased in the successively fractionated C(18) cartridge-adsorbed fraction (SC-ADF). Reporter gene activation by SC-ADF was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the effect is estrogen receptor dependent. However, SC-ADF failed to activate the androgen receptor in COS cells transfected with the corresponding receptor and reporter plasmids. These data show that extracts of Schizandra chinensis fruit act as a weak phytoestrogen.

Animals↗

PubMed2003

Combined effects of inhaled nitric oxide and a recruitment maneuver in patients with acute respiratory distress syndrome.

Nitric oxide (NO) inhalation therapy has been employed in the management of acute respiratory distress syndrome (ARDS), in order to improve oxygenation. Several factors have been implicated as being responsible for the action of inhaled NO. Alveolar recruitment methods, such as prone positioning and a sufficient positive end expiratory pressure (PEEP), have been identified as having a positive impact on the NO response. A Recruitment maneuver (RM) was introduced for the treatment of ARDS, along with a lung protective strategy. Here, we hypothesized that a RM may further augment the oxygenation of patients treated with NO inhalation. Therefore, the effects of the inhalation of NO, either in combination with a RM, or separately, were evaluated on patients with ARDS for their enhancing action. 23 patients with ARDS were enrolled, and divided into three groups. The patients in group 1 (n=11) were treated with 5 ppm NO via inhalation, followed by a RM, applying a sustained inflation pressure of 30 - 35 cmH2O for 30 seconds. Group 2 (n=6) received a RM alone, while group 3 (n=3) was treated with NO inhalation alone. The oxygenation and hemodynamic parameters were obtained prior to, and 2, 12, and 24 h after, the respective treatment procedures. For group 1, the PaO2/FiO2 increased from its initial value of 171.8 +/- 67.8 to 203.2 +/- 90.0 2 h after NO inhalation. Further improvement was noted with the continual application of the RM reaching, 215.5 +/- 74.6 (p=0.05) and 254.2 +/- 109.5 (p < 0.05), after 12 and 24 h, respectively. Initially 7 of the subjects did not respond to NO inhalation, but 3 of these non-responders changed into responders 12 h after the RM. The changes in the PaO2/FiO2 from baseline at each time period were greater in group 1 than in the other groups, but with no statistical significance. The hemodynamics of the patients was not significantly altered during the entire study period. We conclude that the combined application of NO inhalation and a RM could be beneficial and safe for patients with ARDS, showing an enhancing effect in improvement of oxygenation.

Administration, Inhalation↗

PubMed2003

Ginsenoside Rc and Re stimulate c-fos expression in MCF-7 human breast carcinoma cells.

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

Adenocarcinoma↗