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Biomedical subjects

J J Lee

Publications and source records attributed to J J Lee.

At least 19 recordsLinked to original sources
PubMed2006

Quality of life is predictive of survival in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Patients with unresectable hepatocellular carcinoma (HCC) have a dismal prognosis. The objective of this study was to evaluate whether patient-reported baseline quality of life (QoL) measured by the EORTC QLQ-C30 instrument is predictive of survival for these patients. MATERIALS AND METHODS: Two hundred and thirty-three patients with unresectable HCC (mainly hepatitis B-associated) who were recruited into two separate randomized phase III clinical studies, based on palliative chemotherapy and palliative hormonal therapy, respectively, gave consent and received pretreatment QoL assessment. EORTC QLQ-C30 scores and clinical variables at the time of study entry were analyzed to identify factors that influenced survival by applying multivariate analysis. Independent prognostic factors for survival were studied by Cox regression analysis. RESULTS: Median survival of the 233 patients was 5.5 months (95% CI 4.2-6.5 months). Significant independent predictors of shorter survival were advanced Okuda staging (P = 0.0030; HR = 2.058), high baseline total bilirubin (P = 0.0008; HR = 1.013) and worse QoL score in the appetite score domain (P = 0.0028; HR for 10 point increase = 1.070). Patients who were entered into the chemotherapy trial (P = 0.0002; HR = 0.503), those who scored better in the physical functioning domain (P = 0.0034; HR for 10 point decrease = 0.911) and the role functioning domain (P = 0.0383; HR for 10 point decrease = 0.944) of the QoL questionnaire, were associated with longer survival. CONCLUSIONS: In the studied HCC population, patient-reported baseline QoL provides additional prognostic information that supplements traditional clinical factors, and is a new prognostic marker for survival for patients with unresectable HCC.

Adolescent↗
PubMed2006

Improved therapeutic outcomes of DLBCL after introduction of rituximab in Korean patients.

The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact of this combination therapy on DLBCL outcomes in Korea. From October 2001 to June 2004, newly diagnosed DLBCL patients in nine Korean institutes were included. All of these 81 patients were treated with three or more cycles of rituximab plus CHOP (R-CHOP) combination chemotherapy (R group), and followed for a minimum of 12 months. For comparison, a historical cohort of patients was used and analyzed for "Clinicopathologic characteristics of Korean non-Hodgkin's lymphomas (NHLs) based on Revised American Lymphoma (REAL) classification" in 1999. Among the 1,098 NHL patients, the data of 214 DLBCL patients, who were treated with CHOP chemotherapy in first-line, were analyzed (C group). We compared outcomes between the C group and the R group. A total of 295 patients were evaluated (C group, 214; R group, 81). The complete response (CR) rate was higher in R group (73 vs 91%, p=0.001). The 2-year event-free survival (EFS) rate was significantly higher in R group (78 vs 85%, p=0.0194). This survival benefit was maintained in high-risk patients according to the international prognostic index (IPI) (p=0.0039), regardless of age. However, there was no significant difference in low-risk patients. The addition of rituximab to CHOP combination chemotherapy for DLBCLs showed improved outcomes, particularly in high-risk group according to the IPI. Long-term follow-up results will be needed to confirm these results.

Adolescent↗
PubMed2006

CYP2D-related metabolism in animals of the Canoidea superfamily - species differences.

CYP2D-related drug metabolism in liver microsomes from animals of the Canoidea super family, i.e. mink (Mustela vison), bears (Ursus arctos), foxes (Vulpes vulpes) and dogs, were investigated. Propranolol, bunitrolol and imipramine, which are typically substrates of CYP2D subfamilies, were used in the experiment. All the animals of the Canoidea superfamily that were tested lacked the ability to catalyse 7-hydroxylation of propranolol, which is one of the major metabolic pathways in rats. Stereoselectivity of propranolol metabolism was towards (S)-propranolol in all the reactions of the animals tested with the exception of mink, which showed a selective tendency towards (R)-propranolol in N-dealkylation. As far as metabolic patterns of (R)- and (S)-propranolol are concerned, bears, foxes and dogs are alike, but minks are somewhat different. Liver microsomes from mink showed, among the animals of the Canoidea superfamily, the lowest propranolol hydroxylase activity at 4- and 5-positions and imipramine 2-hydroxylation and {N-}demethylation activities. We could not detect bunitrolol 4-hydroxylation in mink liver microsomes at the low substrate concentration used. We conclude that mink have the lowest activity of CYP2D-related xenobiotic metabolism among the Canoidea superfamily.

Adrenergic Uptake Inhibitors↗
PubMed2006

Association of melanocortin 4 receptor (MC4R) and high mobility group AT-hook 1 (HMGA1) polymorphisms with pig growth and fat deposition traits.

The aim of this study was to analyse the combined effect of melanocortin 4 receptor (MC4R) and high mobility group AT-hook 1 (HMGA1) polymorphisms on growth and fatness traits in Duroc pigs. No significant interaction was observed between MC4R and HMGA1 for back-fat traits. An additive mode of inheritance of both gene effects was found for average daily gain and lean meat content. Maximum mean differences from combined genotypic effects were over 2 mm for back fat, 70 g/day for average daily gain and 2% for lean meat content. Therefore, utilization of polymorphisms in both MC4R and HMGA1 for marker-assisted selection could result in an economic benefit to the pig industry.

Animals↗
PubMed2006

Parameter sensitivity analysis for activated sludge models No. 1 and 3 combined with one-dimensional settling model.

The aim of this study was to suggest a sensitivity analysis technique that can reliably predict effluent quality and minimize calibration efforts without being seriously affected by influent composition and parameter uncertainty in the activated sludge models No. 1 (ASM1) and No. 3 (ASM3) with a settling model. The parameter sensitivities for ASM1 and ASM3 were analyzed by three techniques such as SVM-Slope, RVM-SlopeMA, and RVM-AreaCRF. The settling model parameters were also considered. The selected highly sensitive parameters were estimated with a genetic algorithm, and the simulation results were compared as deltaEQ. For ASM1, the SVM-Slope technique proved to be an acceptable approach because it identified consistent sensitive parameter sets and presented smaller deltaEQ under every tested condition. For ASM3, no technique identified consistently sensitive parameters under different conditions. This phenomenon was regarded as the reflection of the high sensitivity of the ASM3 parameters. But it should be noted that the SVM-Slope technique presented reliable deltaEQ under every influent condition. Moreover, it was the simplest and easiest methodology for coding and quantification among those tested. Therefore, it was concluded that the SVM-Slope technique could be a reasonable approach for both ASM1 and ASM3.

Algorithms↗
PubMed2006

Identification of the adverse effect of nitrate on the phosphate release rate and improvement of EBPR process models.

The adverse effect of nitrate on the phosphate release rate in the anaerobic phase was observed and was hardly explainable with conventional EBPR process models. Four possible mechanisms were proposed including substrate competition, reduced fermentation, parallel reaction and sequential reaction. Batch experiments were designed and conducted to identify the dominant mechanism. Results showed that the sequential reaction was the only possible mechanism where only denitrification occurred if any nitrate existed in the anaerobic phase. Then the phosphate release following after the nitrate was completely removed. Nitrate inhibition effect was added into the PHA storage rate to incorporate the sequential reaction in the conventional ASM3 plus EAWAG bio-P module (ASM3 + P). Nitrate inhibition coefficient, K(I,NO,PAO) was found to be as low as 0.05 mg/L. This correlated well with experimental observation where no also meant that the anaerobic compartment of a continuous flow reactor could be seriously affected by the residual nitrate contained in the sludge recycle flow. This phenomenon caused overestimation of the phosphate uptake rate and consequently underestimation of PO4(3-) -P concentration. This problem was resolved by incorporation of a nitrate inhibition term in the ASM3 + P for more accurate simulation of the EBPR process.

Bacteria, Anaerobic↗
PubMed2006

Enhancing flexible fiber filter (3FM) performance using in-line coagulation.

A new packing for deep bed filtration using Flexible Fibers has been proposed and developed on a very large scale for tertiary treatment of wastewater. The purpose of this study is to check the possibility of using this technology for the production of drinking water from surface water. In this study, the feasibility of the fiber filter application on water treatment was examined and the removal efficiency of fiber filter was improved using an in-line coagulant injection method. The experiments were carried out at pilot scale. The filter was packed with bundles of polyamide fibers with a bed porosity of 93%. Nak-dong River was used as the filter influent water and alum, PSOM, and PAC were used as the coagulants. The coagulants were injected by the in-line injection method. Small dosages (1-5 mg/L) of the polymeric coagulants (PSOM and PAC) showed an increase of removal efficiency compared to the operation without coagulants. Specifically, 1 mg/L of PAC showed the longest filtration time. Considering filtration time, filtrate quality, and filtered volume, the filtration velocity of 120 m/hr was chosen as an optimum value. For long-term operations, the effluent quality was 0.4 NTU and the removal efficiency was stable for the given optimum conditions.

Filtration↗
PubMed2005

Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit.

Betel quid (BQ) chewing is popular in Taiwan, India, and many southeast-Asian countries. BQ chewing has strong association with the risk of oral leukoplakia (OL), oral submucous fibrosis (OSF), and oral cancer (OC). BQ components exhibit genotoxicity and may alter the structure of DNA, proteins and lipids, resulting in production of antigenicity. BQ ingredients are also shown to induce keratinocyte inflammation by stimulating the production of prostaglandins, TNF-alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in keratinocytes. These events may provoke tissue inflammation, early cell-mediated immunity (CMI), and immune surveillance in BQ chewers. However, BQ components also directly affect the functional activities of immunocompotent cells, and moreover tumor cells may hypo-respond to the CMI via diverse mechanisms such as induction of apoptosis of lymphocytes, induction of production of suppressor T cells, downregulation of MHC molecules in tumor cells, etc. Clinically, an alteration in lymphocyte subsets, a decrease in total number of lymphocytes, and a reduction in functional activities of CMI have been observed in isolated peripheral blood mononuclear cells (PBMC) and tumor infiltrated lymphocytes (TIL) in patients with OSF, OL or OC. Adaptation of tumor cells to immune system may promote clonal selection of resistant tumor cells, leading to immune tolerance. Future studies on effects of BQ components on CMI and humoral immunity in vitro and in vivo can be helpful for chemoprevention of BQ-related oral mucosal diseases. To elucidate how virus infection, tobacco, alcohol and BQ consumption, and other environmental exposure affect the immune status of patients with oral premalignant lesions or OC will help us to understand the immunopathogenesis of OC and to develop immunotherapeutic strategies for OC.

Areca↗
PubMed2005

Distribution of productive antigen-processing activity for MHC class II presentation in macrophages.

We demonstrated that an epitope from the recombinant protective antigen (rPA) of Bacillus anthracis was presented by mature major histocompatibility complex class II (MHC-II) molecules, whereas an epitope from the recombinant virulent (rV) antigen of Yersinia pestis was presented by newly synthesized MHC-II. We addressed which endosomal compartments were involved in the antigen processing of each epitope. Bone-marrow-derived macrophages were subjected to subcellular fractionation; fractions were analysed for the expression of endosomal markers and used as a source of enzyme activity for the processing of rPA and rV antigens. The rPA epitope was productively processed by dense lysosomal fractions and light membrane fractions expressing early endosomal markers Rab5 and early endosomal antigen-1 as well as markers of antigen-presenting compartments (MHC-II, DM, DO and Ii chain). In contrast, the rV epitope was productively processed only by dense fractions with lysosomal activity. No productive antigen-processing activity was associated with fractions of intermediate density expressing Rab7 and Rab9, characteristic of late endosomes. The data suggest that endosomal compartments expressing Rab5 guanosine triphosphatase can productively process protein antigens for presentation by mature MHC class II molecules.

Amino Acid Sequence↗
PubMed2005

A new Hypocrea strain producing harzianum A cytotoxic to tumour cell lines.

AIMS: To identify a new fungal strain, Hypocrea sp. F000527 producing a trichothecene metabolite, harzianum A, and to evaluate its cytotoxicity to tumour cell lines. METHODS AND RESULTS: A fungal strain, F000527, with cytotoxic activity was identified as a new Hypocrea strain based on morphological characteristics and internal transcribed spacers rDNA sequence data. Harzianum A was isolated from wheat bran culture by 50% acetone extraction, silica gel chromatography, Sephadex LH-20 chromatography and HPLC. The chemical structures were determined by ESI- or HRFAB-MS and (1)H and (13)C-NMR analyses. Harzianum A showed cytotoxicity to HT1080 and HeLa cell lines with IC(50) value of 0.65 and 5.07 Łg ml(-1) respectively. CONCLUSIONS: Harzianum A with a chemical formula of C(23)H(28)O(6) was isolated from a new Hypocrea strain and showed moderate to strong cytotoxicity to human cancer cell lines. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of the production of cytotoxic harzianum A by a new Hypocrea strain.

Antineoplastic Agents↗
PubMed2005

Type III secretion of the Salmonella effector protein SopE is mediated via an N-terminal amino acid signal and not an mRNA sequence.

Type III secretion systems (TTSS) are virulence-associated components of many gram-negative bacteria that translocate bacterial proteins directly from the bacterial cytoplasm into the host cell. The Salmonella translocated effector protein SopE has no consensus cleavable amino-terminal secretion sequence, and the mechanism leading to its secretion through the Salmonella pathogenicity island 1 (SPI-1) TTSS is still not fully understood. There is evidence from other bacteria which suggests that the TTSS signal may reside within the 5' untranslated region (UTR) of the mRNA of secreted effectors. We investigated the role of the 5' UTR in the SPI-1 TTSS-mediated secretion of SopE using promoter fusions and obtained data indicating that the mRNA sequence is not involved in the secretion process. To clarify the proteinaceous versus RNA nature of the signal, we constructed frameshift mutations in the amino-terminal region of SopE of Salmonella enterica serovar Typhimurium SL1344. Only constructs with the native amino acid sequence were secreted, highlighting the importance of the amino acid sequence versus the mRNA sequence for secretion. Additionally, we obtained frameshift mutation data suggesting that the first 15 amino acids are important for secretion of SopE independent of the presence of the chaperone binding site. These data shed light on the nature of the signal for SopE secretion and highlight the importance of the amino-terminal amino acids for correct targeting and secretion of SopE via the SPI-1-encoded TTSS during host cell invasion.

Amino Acid Motifs↗
PubMed2004

Reversible changes in adrenocorticotropin (ACTH)-induced adrenocortical steroidogenesis and expression of the peripheral-type benzodiazepine receptor during the ACTH-insensitive period in young rats.

We previously demonstrated decreased adrenal content of a mitochondrial cholesterol transporter [peripheral-type benzodiazepine receptor (PBR)] during the first postnatal week in rats, when ACTH-inducible steroidogenesis is low. Here we report that the expression of PBR protein and mRNA increases throughout the neonatal/juvenile period in rats in parallel with ACTH-inducible steroidogenesis in vitro. We also previously reported that chronic stimulation of rat pups with daily ACTH injections augmented the steroidogenic response of the developing adrenal cortex. We therefore tested the hypotheses that the change in phenotype induced by ACTH was permanent, and that the effects of ACTH were mediated by increased PBR expression. Pups were injected with ACTH or saline from postnatal d (pd) 2-8 or 2-14. Another group of pups received ACTH from pd 2-7, followed by saline from pd 8-14. On the final day, all pups were challenged with a test injection of ACTH or saline. Exposure to ACTH, but not saline, for 1 wk significantly increased adrenal mass, the corticosterone response to ACTH, and the expression of PBR protein and mRNA. Continued ACTH treatment for a second week maintained adrenal mass, steroidogenesis, and PBR mRNA expression. When ACTH was withdrawn after 1 wk and replaced with daily saline injections, however, adrenal mass, ACTH-inducible steroidogenesis, and PBR expression returned to levels comparable to those in age-matched saline controls (i.e. animals that had not received ACTH injections during the first 2 wk). Thus, although ACTH was capable of inducing increased steroidogenic capacity of the juvenile rat adrenal, its effects were only manifest when pups were exposed regularly to high plasma ACTH levels. ACTH, therefore, has significant, but reversible, effects on the development of adrenocortical function, possibly mediated in part by increased expression of PBR.

Adrenal Cortex↗
PubMed2004

Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells.

Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (delta Psim) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 microM) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05-0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.

Antioxidants↗
PubMed2004

Robust motor speed control under time varying loads in moving actuator type artificial heart (AnyHeart).

The Moving Actuator type artificial heart(AnyHeart) as well as many other artificial hearts uses a motor as its power source. For controllability of control parameters such as pump rate, pump output, blood pressure profile and flow form, the precise motor speed control is important. However, because the implantable device has limited carrying capacity of hardware components in size and number, applying diverse motor control methods are not possible. In addition, the existing PI (Proportional-Integral) motor controller does not show satisfactory performance. A new controller that is sufficiently robust for the changes of load and physical system parameters has been designed and tested. The robust speed controller is based on the sliding mode control method that is applicable to a system of which the ranges of uncertainty in physical parameters are known. In a mock circulation system test, the actual speed showed good tracking characteristics in respect to the reference speed. Fast follow-up characteristics were also observed under high afterload and speed conditions. The speed error, current and power consumption were reduced by about 40%. The proposed control technique overcomes the limitations of the PI controller, and makes important improvements in both performance and stability.

Algorithms↗
PubMed2004

Optociliary shunt vessels in diabetes mellitus.

INTRODUCTION: Optociliary shunt vessels is classically described to be associated with optic nerve sheath meningioma, with the triad symptoms of optociliary veins, disc pallor and visual loss. Other clinical settings include retinal vein occlusion, chronic glaucoma, meningioma, and rarely as a congenital form. We report an interesting case series of three patients with diabetes mellitus presenting with optociliary shunts. METHODS: Patients who underwent diabetic retinopathy screening were referred to the eye clinic for abnormal findings. Between 2000 and 2001, out of a total of 3,360 patients, three diabetic patients with optociliary shunt vessels were found (0.1 percent). Optociliary shunt vessels were documented with fundus photography and fundal fluorescein angiography. RESULTS: All three patients had bilateral mild nonproliferative diabetic retinopathy with one having, in addition, bilateral diabetic maculopathy. Fluorescein angiography showed classical features of acquired optociliary shunts with no leakage. Systemic review did not show any secondary cause of the optociliary shunts. CONCLUSION: Our case series showed that optociliary veins can be associated with diabetes mellitus. The authors postulate that it may be due to venous insufficiency secondary to the process of diabetic microangiopathy and venous stasis.

Diabetic Retinopathy↗
PubMed2004

A study of NH3-N and P refixation by struvite formation in hybrid anaerobic reactor.

This research is concerned with the removal of ammonia nitrogen and phosphorus in foodwaste by crystallization. Reductions have been achieved by struvite formation after the addition of magnesium ions (Mg2+). Magnesium ions used in this study were from magnesium salts of MgCl2. The results of our analysis using scanning electron microscopy and energy dispersive X-ray analysis showed that the amount of struvite in precipitated sludge grew enough to be seen with the naked eye (600-700 microm). EDX analysis also showed that the main components of the struvite were magnesium and phosphorus. NH3-N removal efficiency using MgCl2 was 67% while PO4-P removal efficiency was 73%. It was confirmed that nitrogen and phosphorus could be stabilized and removal simultaneously through anaerobic digestion by Mg, NH3 and PO4-P, which were necessary for struvite formation.

Ammonia↗
PubMed2003

Anticonvulsant dicarboxyphenylglycines differentially modulate excitatory amino acid release in the rat cerebral cortex.

The 3,4-dicarboxyphenylglycines (3,4-DCPGs) have recently been shown to be effective new anticonvulsant agents in a rodent model of epilepsy, with the racemic mixture showing significantly greater potency than either isomer alone. The (R)-isomer has been identified as a competitive AMPA-type ionotropic glutamate receptor antagonist, whilst (S)-3,4-DCPG is a highly potent and selective metabotropic glutamate receptor 8 (mGlu8 receptor) agonist. We now report the inhibitory activity of (R)- and (RS)-3,4-DCPG, but not (S)-3,4-DCPG, against both 35 mM and 50 mM KCl-evoked glutamate release in the rat cerebral cortex in vitro. In contrast to the anticonvulsant actions of the 3,4-DCPGs, no evidence was obtained for a synergistic inhibitory interaction between the separate isomers. We conclude that whilst inhibition of cortical excitatory amino acid release may contribute to the anticonvulsant actions of (RS)-3,4-DCPG, it does not represent the sole mechanism of action. Synergistic interactions between ligands acting at different subtypes of ionotropic and metabotropic glutamate receptors remains a promising new strategy for the treatment of currently drug-refractory seizure states.

Animals↗