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Biomedical subjects

D Y Lee

Publications and source records attributed to D Y Lee.

At least 37 records · Page 2Linked to original sources
PubMed2001

Suppression of tumorigenicity and metastasis in B16F10 cells by PTEN/MMAC1/TEP1 gene.

PTEN/MMAC1/TEP1 (PTEN) is a tumor suppressor gene that is mutated in a variety of advanced and metastatic cancers, strongly suggests that PTEN alteration is possibly involved in the tumor progression and formation of metastases. However, the roles of PTEN in tumor growth and metastasis and its functional mechanisms are not fully understood. We evaluated the tumor suppressor function of PTEN gene on tumor growth and metastasis in vitro and in vivo. Our results of in vitro soft agar assay and in vivo PTEN-expressing tumor cell growth showed that PTEN inhibited the tumorigenicity of B16F10 melanoma cells. Anti-metastatic function of PTEN was also revealed by experimental pulmonary metastatic animal model. For the further insight into the mechanisms underlying the PTEN-mediated inhibition of tumor metastasis, we have examined the role of PTEN on the secretion of matrix metalloproteinases (MMPs), insulin-like growth factors (IGFs) and the expression of secretory and cellular vascular endothelial growth factor (VEGF) proteins that have been described to contribute to the metastasis of tumor. PTEN significantly lowered MMPs and IGFs secretion and also expression of secretory and cellular VEGF proteins. These results suggest that PTEN tumor suppressor protein inhibits tumorigenicity and metastasis through regulation of MMP, IGFs, and VEGF expression.

Animals↗
PubMed2001

Mutational effects on thermostable superoxide dismutase from Aquifex pyrophilus: understanding the molecular basis of protein thermostability.

We designed two mutants of superoxide dismutase (SOD), one is thermostable and the other is thermolabile, which provide valuable insight to identify amino acid residues essential for the thermostability of the SOD from Aquifex pyrophilus (ApSOD). The mutant K12A, in which Lys12 was replaced by Ala, had increased thermostability compared to that of the wild type. The T(1/2) value of K12A was 210 min and that of the wild type was 175 min at 95 degrees C. However, the thermostability of the mutant E41A, which has a T(1/2) value of 25 min at 95 degrees C, was significantly decreased compared to the wild type of ApSOD. To explain the enhanced thermostability of K12A and thermolabile E41A on the structural basis, the crystal structures of the two SOD mutants have been determined. The results have clearly shown the general significance of hydrogen bonds and ion-pair network in the thermostability of proteins.

Bacterial Proteins↗
PubMed2001

Fumonisin B(1) induces apoptosis in LLC-PK(1) renal epithelial cells via a sphinganine- and calmodulin-dependent pathway.

Fumonisins are a family of mycotoxins produced by Fusarium moniliforme, which is the most common mold found on corn throughout the world. These compounds are both toxic and carcinogenic for animals, and perhaps humans, with the kidney being the most sensitive organ to fumonisin toxicity. The molecular mechanism of fumonisin toxicity appears to involve disruption of de novo biosynthesis of sphingolipids and accumulation of sphinganine. The goals of this study were to determine whether fumonisin B(1) kills LLC-PK(1) renal kidney epithelial cells by inducing apoptosis and to identify genes affected by sphinganine that mediate fumonisin B(1)-induced cell death. Fumonisin B(1) produced morphological changes (i.e., cell shrinkage, membrane blebbing) and time-dependent increases in DNA fragmentation demonstrating that the toxin induces apoptosis. Simultaneously, fumonisin B(1) blocked sphingolipid biosynthesis and caused accumulation of sphinganine. To further investigate the role of sphinganine in fumonisin B(1)-induced apoptosis, beta-fluoroalanine (betaFA) was used to inhibit serine palmitoyltransferase, which catalyzes an earlier step in the sphingolipid biosynthetic pathway. betaFA blocked sphinganine accumulation and prevented fumonisin B(1)-induced DNA fragmentation, confirming that apoptosis induced by fumonisin B(1) is dependent upon accumulation of sphinganine. To examine gene expression, differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) was applied to RNA isolated after 16 h of exposure to fumonisin B(1). Differential expression in response to fumonisin B(1) of a gene identified as calmodulin has been verified by Northern analysis. Sphinganine appears to mediate the effect because betaFA reduces induction of calmodulin mRNA by fumonisin B(1). Fumonisin B(1) also increases calmodulin protein in a concentration-dependent manner and the calmodulin antagonist W7 blocks fumonisin B(1)-induced DNA fragmentation, supporting a role for calmodulin in fumonisin B(1)-induced apoptosis. In contrast, fumonisin B(1) had no effect on expression of bcl-2 family genes (bax, bcl-2, and bcl-x). These findings demonstrate that fumonisin B(1) kills LLC-PK(1) kidney cells by inducing apoptosis. Further, the results establish a sequence of events for fumonisin B(1)-induced apoptosis involving initial disruption of sphingolipid metabolism and accumulation of sphinganine (or a metabolite), which, in turn, induces expression of calmodulin.

Alanine↗
PubMed2001

Transferrin C2 variant does not confer a risk for Alzheimer's disease in Koreans.

We analyzed the transferrin (TF) and apolipoprotein E (APOE) genotypes of 164 probable Alzheimer's disease (AD) patients and 239 cognitively normal elderly controls in Koreans. We failed to detect a significant difference in genotypic frequencies and allelic frequencies of the TF polymorphism between the AD group and control group (P>0.1 by Chi square test). The frequency of the TF C2 variant did not differ by the diagnosis when the APOE epsilon4-positive subjects and APOE epsilon4-negative subjects were analyzed separately (P>0.1 by Chi square test). The TF C2 variant did not influence the age-at-onset of AD independently or synergistically with the occurrence of the APOE epsilon4 allele (P>0.1 by ANOVA). The TF C2 variant did not confer a risk for AD in Koreans.

Age Factors↗
PubMed2001

Association of alpha-2-macroglobulin deletion polymorphism with sporadic Alzheimer's disease in Koreans.

Alpha-2-macroglobulin (A2M) deletion polymorphism was recently reported to be associated with Alzheimer's disease (AD) in a way comparable to apolipoprotein E (APOE) polymorphism in a family-based study. However, the association of A2M deletion polymorphism with AD has not been consistently replicated in successive case-controlled studies. In order to evaluate whether this A2M polymorphism is associated with AD in Koreans, we examined the frequencies of the A2M deletion (D) allele and D-bearing genotypes in a group of Koreans composed of 100 sporadic AD patients and 203 control subjects. The frequency of the deletion (D) allele (P=0.046) was significantly different between the total group of AD patients and the controls, although the frequency of the D-bearing genotypes did not attain significance (P=0.078). When the subjects were stratified according to age at onset, there was significant difference in the frequencies of the D allele (P=0.044) and D-bearing genotypes (P=0.041) between late-onset AD patients (> or =65 years) and the controls. However, no significant difference was observed between early-onset AD patients (<65 years) and the control group. Additionally, when we divided the late-onset AD and control subjects by APOE epsilon4 status, the difference of the A2M D allelic frequency was significant only in the APOE epsilon4 negative subjects (P=0.015). In conclusion, our data suggests that the A2M D allele is a modest risk factor for late-onset sporadic AD in Koreans, and the AD risk conferred by the A2M D allele increases in APOE epsilon4 negative subjects.

Aged↗
PubMed2001

Structural characterization of the 60-kDa bermuda grass pollen isoallergens, a covalent flavoprotein.

Our studies suggest a tripartite structure for the 60-kDa allergen of Bermuda grass pollen (BG60) including a short N-terminal segment, a FAD-binding domain, and a C-terminal domain. The lower molecular weight isoallergens lack the N-terminal segment. The higher protease susceptibility and the lower melting temperature of approximately 20 degrees C of the lower molecular weight isoforms suggest that the N-terminal segment is essential for a compact structure. Database screening reveals that the protease-digested peptide sequences (approximately 180 residues in total) share 40% identity with the plant berberine bridge enzymes. In particular, a 24-residue peptide sequence displays high similarity to a conserved FAD-binding motif. The spectroscopic and SDS-PAGE analyses suggest that the cofactor FAD is covalently linked to the central domain. Therefore, we conclude that BG60 is identified as the first flavinylated allergen.

Allergens↗
PubMed2001

Neither the butyrylcholinesterase K variant nor transferrin C2 variant confers a risk for Alzheimer's disease in Koreans.

To investigate the possible involvement of the butyrylcholinesterase (BCHE) K variant and transferrin (TF) C2 variant in the manifestation of Alzheimer's disease (AD), we analyzed the BCHE, TF and apolipoprotein E (APOE) genotypes of 164 sporadic AD patients and 239 normal elderly controls. The frequencies of the BCHE K and TF C2 did not differ between the AD patients and controls (P > 0.1). The occurrence of the APOE epsilon4 did not influence the distribution of the BCHE K and TF C2 variants (P > 0.1). No linkage disequilibrium between the BCHE K and TF C2 was observed either in both the AD patients and controls (P > 0.1). In conclusion, neither the BCHE K nor the TF C2 confers a risk for AD.

Aged↗
PubMed2001

Neurologic outcomes of pediatric epileptic patients with pentobarbital coma.

Status epilepticus is a life-threatening condition requiring emergent medical attention. Although initial therapies with antiepileptic drugs generally terminate seizures within 30 to 60 minutes, patients with refractory status epilepticus require additional intervention. High-dose pentobarbital has been the most commonly prescribed agent for the management of refractory status epilepticus in children. The objective of this research was to evaluate the association between the response of pentobarbital coma and neurologic outcomes in refractory status epilepticus. Twenty-three subjects were treated with pentobarbital coma for at least 48 hours. Medical records were reviewed to collect patient demographic information, responses to treatment, and neurologic outcomes. Among the 23 patients reviewed, 12 patients were controlled with pentobarbital (responders), six were unresponsive to pentobarbital (nonresponders), and five patients relapsed after discontinuation or during tapering of pentobarbital (relapser). The mortality rate among the relapser and nonresponder groups combined was 90.9%, but no deaths occurred among the responder group (P < 0.001). The survival rate was greater among toddlers compared with neonates or older children. Failure of seizure control after pentobarbital coma was associated with a poor prognosis. The potential for serious complications of pentobarbital therapy among neonates highlights the need for careful dosing in this age group.

Adolescent↗
PubMed2001

Expression of the insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) in human gastric cancer cells.

Insulin-like growth factor (IGF)-I and -II are potent mitogens and postulated to exert autocrine, and paracrine effects on growth regulation in human gastric cancer. Their mitogenic effects are tightly regulated by the IGF binding proteins (IGFBPs). In this study, we evaluated the mRNA expression of IGF-I, IGF-II and the IGFBPs in a panel of human gastric cancer cell lines, and normal and tumour tissue specimens from patients with gastric cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and competitive PCR. Conditioned media (CM) of the gastric cancer cell lines were studied for the secretion of the IGFBPs by western ligand blot (WLB) and western immunoblot (WIB). IGF-I and IGF-II were expressed in all of the gastric cancer cell lines, and the normal and tumour tissue specimens. Overexpression of the IGFs, in particular, IGF-II, was observed in the tumour tissues. The expression pattern of IGFBPs was heterogeneous among the gastric cancer cell lines. IGFBP-2 was expressed in all of the gastric cancer cell lines, whereas IGFBP-1 was not detected in any cell lines. IGFBP-4 was expressed in the most of cell lines. IGFBP-3, IGFBP-5 and IGFBP-6 were expressed in approximately 50% of cell lines. In addition, exogenous IGF-I and IGF-II stimulated the proliferation of gastric cancer cells, suggesting the existence of a functional IGF system in gastric cancer. Taken together, our data-suggest that the IGF-IGFBP system may play an important role in the initiation, progression and metastasis of gastric cancer. Further studies are needed to understand the exact role of IGFs and IGFBPs in gastric neoplasia.

Adenocarcinoma↗
PubMed2001

Recycling of wood chips and wheat dregs for sludge processing.

A Buchner filtration study was conducted to investigate the effect on sludge dewatering of adding organic waste solids (wood chips or wheat dregs) to sludge after chemical preconditioning (with ferric chloride or alum). Increasing the dose of wood chips or wheat dregs enhanced sludge filtration performance and increased the energy content of the filter cake, but did not consistently increase the total filtrate removed. The additional filtrate removal was found to balance the inert solids load only when the chemical preconditioner used did not result in sufficient coagulation of the sludge and the skeleton builder dose was low (< or = 90%). Accordingly, various dose ranges of wood chips and wheat dregs are suggested for different sludge management schemes.

Biodegradation, Environmental↗
PubMed2001

Nutrient removal from polluted river water by using constructed wetlands.

The Erh-Ren River is one of the most polluted rivers in Taiwan. Although its flow rate is relatively low, the rate is still beyond the capacity of any traditional water treatment facility. A pilot-scale constructed wetland (CW) is the attempt used to purify the highly polluted river water and to collect data for the construction and operation of a full-scale system in the future. This article reports the results from this initial stage of our research work. During the study, the most efficient nutrient removal occurred between April and October. The monthly average removal rates of chemical oxygen demand (COD) ranged from 13-51% of ammonia-N (AN) from 78-100%, and of orthophosphate (OP) from 52-85%. After November, input COD levels increased, and the monthly average removal rates of ammonia-N dropped to 16% and of orthophosphate to 13%. The dramatic changes in removal efficiency suggest that the macrophytes in the CW had a direct influence on the water treatment and that the change of seasons and the quality of the river water inhibited the growth of the macrophytes.

Ammonia↗
PubMed2001

Elective endovascular treatment of descending thoracic aortic aneurysms and chronic dissections with stent-grafts.

PURPOSE: To report our experience of endovascular stent-graft placement in patients with descending thoracic aortic dissections and aneurysms and to evaluate the feasibility, safety, and clinical outcomes of the treatment. MATERIALS AND METHODS: Stent-grafts were placed in the descending thoracic aortas of 23 patients with saccular aneurysms (n = 11) and Stanford type B chronic aortic dissections of the descending thoracic and abdominal aorta (n = 12). All stent-grafts were individually constructed of self-expandable stainless steel stents covered with polytetrafluoroethylene. Vascular access was achieved through the femoral artery in all patients. Clinical status of each patient was monitored and postoperative CT was performed within 1 month of the procedure and at 3-12-month intervals after the procedures. RESULTS: Successful exclusion of the primary entry tears of dissections and the inlets of saccular aneurysms was achieved in all but two patients with aortic dissection. The overall technical success rate was 91.3% (dissection: 10 of 12 = 83%; aneurysm: 11 of 11 = 100%). All patients in whom technical success was achieved showed complete thrombosis and significant decrease in diameter of the thoracic false lumen (preoperative: 5.3 cm +/- 0.9; postoperative: 4.3 cm +/- 0.9; P = .004) or aneurysm sac (preoperative: 5.3 cm +/- 1.7; postoperative: 2.8 cm +/- 2.5; P = .001). In addition, five patients demonstrated complete resolution of the dissected thoracic false lumen (n = 2) and aneurysm sac (n = 3). However, in all patients with aortic dissection, the abdominal aorta was not significantly changed in size (P = .302) and shape and their false lumen flows remained persistent. Immediate postoperative complications were detected in 12 patients (52%); 10 had fever, leukocytosis, and elevation of C-reactive protein, another had wound infection, and another had transient abdominal pain. Three patients died 2, 3, and 12 months after the procedure: one from septic shock, another from underlying mediastinitis, and the other from an unexplained cause. The remaining 20 patients were well after the procedure (1-9 days; mean, 3 days), without any stent-graft-related complications or discomfort (follow up period: 10-65 mo; mean: 25.1 mo +/- 15.6). The cumulative survival rate after the stent graft was 100% at 30 days and 91% at 12 months. CONCLUSIONS: For treatment of aortic dissection and saccular aneurysm of the descending thoracic aorta, endovascular stent-graft repair may be a technically feasible and effective treatment modality.

Adult↗
PubMed2001

Percutaneous peritoneovenous shunt creation for the treatment of benign and malignant refractory ascites.

Peritoneovenous shunt placement has been reported as a treatment of refractory ascites by general surgeons, but without a clearly established role. The authors successfully inserted shunts under ultrasonographic and fluoroscopic guidance in 12 patients who had symptomatic refractory ascites (nine men, three women; mean maintenance duration, 88.5 d). Nine patients had advanced liver cirrhosis (five with superimposed hepatoma). Other patients had stomach cancer, colon cancer, and complicated polycystic kidney disease. The mortality rate was 83%. Causes of death included bleeding from preexisting varices, sepsis, hepatic failure, rupture of hepatoma, and disseminated intravascular coagulation. The authors describe the feasibility, technical details, and short-term results of percutaneous peritoneovenous shunt placement.

Adult↗
PubMed2001

Enhancing the dewaterability and amenability of sludge for subsequent stabilization processes by using organic waste solids as conditioners.

Dual-material conditioning of sludge was evaluated using a chemical conditioner (either alum or ferric chloride), followed by a physical conditioner (either wood chips or wheat dregs). The combined effects of the conditioners on the dewaterability of the sludge with vacuum filtration and the amenability of the resulting sludge cake for subsequent stabilization processes were investigated. Results showed that the specific resistance of the conditioned sludge was effectively reduced when the dose of wood chips or wheat dregs was increased in each dual-material combination. From the results of analysis of solids in the cake, the filtered sludge cake with either wood chips or wheat dregs conditioning in higher dosage resulted in lower moisture and higher volatile combustible solids content. Accordingly, sludge conditioning with these two materials substantially increased the heating value of the dewatered sludge. In addition, wood chips are the most widely used bulking agent, and wheat dregs could be suitable to act as amendments in sludge composting. These results indicate that these two organic waste solids could replace a significant portion of the chemicals now used for sludge conditioning to improve the dewaterability of sludge and the amenability of the resulting sludge cake for incineration and composting processes.

Conservation of Natural Resources↗
PubMed2001

Pulmonary peptide delivery: effect of taste-masking excipients on leuprolide suspension metered-dose inhalers.

The purpose of this study was to evaluate the effect of taste-masking excipients on in vitro and in vivo performance of a leuprolide metered-dose inhaler (MDI) suspension formulation. Taste-masking excipients (aspartame and menthol) were added to a leuprolide suspension MDI formulation. The leuprolide MDI formulation with the taste-masking excipients was characterized in terms of milling time, particle size distribution, dose delivery and uniformity, and drug absorption in dogs. The data were compared with a formula that did not contain taste-masking excipients. It was found that the longer milling time for the leuprolide suspension with the taste-masking excipients was required to obtain a similar particle size distribution compared with the formula without taste-masking excipients using a fluid energy mill. Although measurable differences in mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were not observed between the two formulations, the percent of particles < or = 5 microns and the actuator retention for the formula with the taste-masking excipients were significantly different from the formula without taste-masking excipients using the Marple-Miller cascade impactor. Taste-masking excipients did not show a significant effect on valve delivery and through-can dose uniformity. However, the mean ex-actuator dose was 150.4 mg for the formula with the taste-masking excipients and 162.2 mg for the reference formula, respectively, indicating a significant difference. In tracheostomized dogs, both formulations showed comparable pharmacokinetic parameters including Cmax, Tmax, AUC0-12 and bioavailability (F%), indicating that the taste-masking excipients do not have an effect on lung absorption of leuprolide acetate. Therefore, inclusion of taste-masking excipients in the leuprolide MDI suspension formulation showed a significant impact on drug micronization, exactuator dose, and particle deposition pattern. Mechanistically, the unfavorable performance of leuprolide MDI in the presence of taste-masking excipients could be due to modification of the properties of the suspension itself and alteration of propellant evaporation following actuation.

Administration, Inhalation↗
PubMed2001

Aortic and arterial aneurysms in behçet disease: management with stent-grafts--initial experience.

PURPOSE: To assess the application of stent-grafts in the management of aortic and arterial aneurysms in patients with Behçet disease. MATERIALS AND METHODS: Nine aneurysms in seven patients were managed with various types of stent-grafts. Diagnoses were based on clinical findings. The aortic aneurysms (n = 3) were thoracic (n = 1), suprarenal (n = 1), or infrarenal (n = 1). The arterial aneurysms (n = 6) were in the right and left subclavian (n = 2), right common carotid (n = 2), right brachiocephalic (n = 1), or left common iliac arteries (n = 1). A tandem connection of Gianturco stent covered with polytetrafluorethylene was placed in three aneurysms, and a balloon-expandable stent was placed in six. RESULTS: The stent-graft was successfully placed in all patients. Immediate follow-up angiography revealed complete exclusion of the aneurysm in all cases. Follow-up computed tomography performed 3 days to 2 weeks later revealed complete exclusion and thrombosis of the aneurysm and patency of the stent-graft in six patients. In one patient, total occlusion of the artery with a stent occurred due to flow disturbance caused by double lesions. During follow-up (range, 6-59 months; mean, 28 months), the aneurysm resolved and completely regressed in four patients. A recurrent aneurysm at the distal margin of previously inserted stent-graft was successfully managed with an additional stent-graft. CONCLUSION: The findings in this initial experience suggest that stent-graft insertion may be a safe and effective alternative to surgical treatment of aortic and arterial aneurysms in patients with Behçet disease.

Adult↗