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Biomedical subjects

J W Lee

Publications and source records attributed to J W Lee.

At least 37 records · Page 2Linked to original sources

Bioanalytical method development and validation for a large peptide HIV fusion inhibitor (Enfuvirtide, T-20) and its metabolite in human plasma using LC-MS/MS.

A method for measuring a human immunodeficiency virus (HIV) cell membrane fusion inhibitor (T-20/Ro 29-9800) and its metabolite (M-20/Ro 50-6343) in human plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. The relatively large peptide analytes and their corresponding deuterated (d(10)) peptides used as internal standard were isolated from plasma by protein precipitation with two volumes of acetonitrile to plasma. A large pore size reversed-phase C(18) column was employed to elute the peptides. A triple quadrupole mass spectrometer with electrospray interface operating in positive ion and multiple reaction monitoring modes with transitions m/z 1124-->1343 for both T-20 and M-20 was utilized for peak detection. The advantages of the method were a simple sample preparation, specific and sensitive MS/MS detection, and a wide dynamic range of 10-2000 ng/ml for T-20. The method was validated and used for analyzing samples from clinical studies to provide pharmacokinetic profiles of the HIV fusion inhibitor peptide drug and its metabolite.

Adsorption↗

Mutation analysis of hepatitis B virus promoters in chronically infected children.

Hepatitis B viral (HBV) infection in early childhood is one of the leading causes of chronic hepatitis and liver cirrhosis that eventually lead to hepatic carcinoma. Despite the nationwide immunization programs to curtail the vertical transmission of HBV, childhood HBV infection through mothers is still occurring in Korea. As one of the efforts to understand the childhood HBV infection in Korea, four HBV promoter sequences in the sera of the chronically infected children were analyzed. Children harbored diverse viral variants as most of the chronically infected adult patients, but the deletion mutations were rare. The dominant viral sequences in the children were highly similar to the ones in the respective mothers, indicating that the maternal viruses were most likely transmitted to the children. The mutations in X, S1, S2/S promoters did not seem to show any correlation to the severity of the disease nor ages of the children. The mutations that showed some correlation to the severity of the disease were the mutations in C promoter, but the mutations did not seem to be vertically transmitted. Finally, the children with the elevated ALT/AST levels tended to have more child-specific variants suggesting that the accumulation of host-specific mutations might be associated with the development of clinical symptoms.

Adolescent↗

Operational strategies for an activated sludge process in conjunction with ozone oxidation for zero excess sludge production during winter season.

A pilot-scale activated sludge system coupled with sludge ozonation process was operated for 112 days of a winter season without excess sludge wasting. The concept of this process is that the excess sludge produced is first disintegrated by ozone oxidation and then recirculated to a bioreactor in order to mineralize the particulate and soluble organic compounds. The basis of operation was to determine either the optimal amount of sludge in kg SS ozonated each day (SO) or the optimal ozonation frequency under the variable influent chemical oxygen demand (COD) loading and temperature conditions, since the ozone supply consumes costly energy. The optimal SO was obtained using the theoretically estimated sludge production rate (SP) and experimentally obtained ozonation frequency (n). While the SP was mainly subject to the COD loadings, sludge concentration was affected by the temperature changes in winter season. The optimal n was observed between 2.5 and 2.7 at around 15 degrees C, but it was doubled at 10 degrees C. Mixed liquor suspended solids (MLSS) concentration was leveled off at around 5000 mg/L in bioreactor at 15 degrees C, but the volatile fraction of MLSS was fixed around 0.7 indicating that there was no significant inorganic accumulation. Suspended solids (SS) and soluble COD in effluents kept always a satisfactory level of 10 and 15 mg/L with sufficient biodegradation. It was recommended to apply a dynamic SO under variable influent COD loadings and temperature conditions to the activated sludge system without excess sludge production for saving energy as well as system stabilization.

Biodegradation, Environmental↗

Preliminary results of consolidation chemotherapy following concurrent chemoradiation after radical surgery in high-risk early-stage carcinoma of the uterine cervix.

AIMS: To evaluate the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) with 5-fluorouracil (5-FU) and cisplatin in the treatment of high-risk, early stage cervical carcinoma after radical surgery. MATERIALS AND METHODS: Women with clinical stage IB and IIA cervical carcinoma, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes, positive margins, parametrial involvement, or all three, were divided into either a CCRT alone group or a consolidation chemotherapy after CCRT group. Three cycles of chemotherapy were given to the CCRT alone group, and six cycles to the consolidation chemotherapy group. Women in each group received 50.4 Gy external radiation in 28 fractions to a standard pelvic field. Chemotherapy consisted of cisplatin 60 mg/m2 (X 1) and 5-FU 1000 mg/m2/d (X 5) every 3 weeks, with the first and second cycles given concurrent with radiation. Survival and toxicity were compared between the two groups. RESULTS: Forty women were evaluable (25 in the CCRT alone group and 15 in the consolidation chemotherapy group). The estimated 2-year progression-free survival was 87.7% in the CCRT alone group and 67.0% in the consolidation chemotherapy group. The estimated 2-year overall survival was 95.8% in the CCRT alone group and 100% in the consolidation chemotherapy group. However, no significant differences were found in progression-free and overall survival in the two groups (P = 0.17 and P = 0.29, respectively). Grade 2 or higher leukopenia and neutropenia were significantly more frequent in the consolidation chemotherapy group than in the CCRT alone group (P = 0.02 and P < 0.01, respectively). CONCLUSIONS: Although the sample size was small, and this study was not randomised, these results suggest that consolidation chemotherapy may not improve survival. Rather, it may increase haematologic toxicities for women with high-risk, early stage cervical carcinoma who undergo radical surgery followed by CCRT.

Adenocarcinoma↗

Small gastrointestinal stromal tumours with focal areas of low attenuation on CT: pathological correlation.

AIM: To describe the pathology of focal areas of low attenuation in small gastrointestinal stromal tumours on contrast-enhanced computed tomography (CT), and to investigate the association of these areas as predictors of malignant potential. MATERIALS AND METHODS: Contrast-enhanced helical CT images were obtained of 39 small (up to 5 cm) gastrointestinal stromal tumours. Focal areas of low attenuation were retrospectively evaluated and correlated with histopathological findings. The relation between the mitotic rate of and the presence of focal areas of low attenuation in the tumours was analyzed using Fisher's exact test. RESULTS: Of the 39 small gastrointestinal stromal tumours, 15 contained focal areas of low attenuation on CT. These were found to be due to solid tumour (n=5), haemorrhage (n=3), haemorrhage with necrosis (n=2), cystic degeneration (n=2), fluid in ulcer (n=2), and fibrous septum (n=1); they were not found to be associated with a high mitotic rate (p=0.45). CONCLUSION: Focal areas of low attenuation on CT in small gastrointestinal stromal tumours represent varying pathological conditions and do not predict malignant potential.

Adult↗

Impact of ABO incompatibility on outcome after allogeneic peripheral blood stem cell transplantation.

Few studies have addressed the incidence of graft-versus-host disease (GVHD) or survival after ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). We analyzed the clinical outcome of ABO incompatibility after allogeneic PBSCT. A total of 89 consecutive adult patients with hematological diseases including 49 ABO-identical, 20 major, 15 minor, and five bidirectional ABO-incompatible transplants were enrolled from four medical centers in Korea. No significant difference in engraftment times, graft failure, or transfusion requirements between groups was noted. A clinical diagnosis of severe immune hemolysis or pure red cell aplasia was not made for any patient after transplantation. The incidence of acute or chronic GVHD did not statistically differ between groups. With a median follow-up duration of 13 months (range, 0.5-61 months), the 3-year overall survival estimates for the ABO-identical, major/bidirectional, and minor group were 44.6.0+/-9.0, 43.1+/-11.6, and 43.8+/-13.5%, respectively (P=0.8652), while the 3-year disease-free survival estimates were 33.8+/-7.6, 39.9+/-11.4, and 45.7+/-13.1%, respectively (P=0.8546). We observed that time to neutrophil, platelet, and red blood cell engraftment, transfusion requirements, incidence of acute or chronic GVHD, relapse, and survival were not influenced by ABO incompatibility after allogeneic PBSCT from HLA-matched sibling donors.

ABO Blood-Group System↗

Effects of green tea extract administration on the pharmacokinetics of clozapine in rats.

The pharmacokinetic interaction between clozapine, an atypical antipsychotic with metabolic complications, including weight gain, and green tea consumption has not been evaluated, although green tea is responsible for beneficial effects, including weight reduction, and is widely consumed in the world. Commercial green tea extract (175 mg kg(-1)) or saline was administered orally for 4 days before the oral administration of clozapine (20 mg kg(-1) ) to rats. Plasma concentrations of clozapine were measured up to 5 h after clozapine administration, and then hepatic CYP1A2 expression and activity were determined. There was no significant difference in the elimination half-life of clozapine between the green tea extract and saline groups. However, the time to reach peak concentration (T(max)) was significantly increased by green tea extract. The mean total area under the plasma concentration-time curve (AUC(0-infinity)) and maximal peak plasma concentration (C(max)) of clozapine in the green tea extract group were significantly lower than those of controls. Green tea extract induced a approximately 2-fold increase in hepatic CYP1A2 levels, while the activity increased slightly (by 10% of control). Because of this reduction in AUC and T(max) of clozapine by green tea extract pretreatment, we suggest that both the rate and amount of absorption of clozapine may be reduced by green tea extract, although the hepatic elimination phase may not be significantly altered. Therefore, the clinical implications of the effects of green tea on the bioavailability of clozapine in patients should be further evaluated.

Animals↗

Genetic structure of pig breeds from Korea and China using microsatellite loci analysis.

To understand molecular genetic characteristics of Korean pigs, the genetic relationships of nine pig breeds including two Korean pigs (Korean native pig and Korean wild pig), three Chinese pigs (Min pig, Xiang pig, and Wuzhishan pig), and four European breeds (Berkshire, Duroc, Landrace, and Yorkshire) were characterized from a 16-microsatellite loci analysis. The mean heterozygosity within breeds ranged from 0.494 to 0.703. Across multiple loci, significant deviation from Hardy-Weinberg equilibrium was observed in most pig breeds, except for two Chinese pigs (Min pig and Wuzhishan pig). This deviation was in the direction of heterozygote deficit. Across population loci, 36 of 144 significantly deviated (P < 0.05) from Hardy-Weinberg equilibrium. The mean FST, a measure of genetic divergence among subpopulations, of all loci indicated that 26.1% of total variation could be attributed to the breed difference. Relationship trees based on the Nei's DA genetic distance and scatter diagram from principal component analysis consistently displayed pronounced genetic differentiation among the Korean wild pig, Xiang pig, and Wuzhishan pig. Individual assignment test using a Bayesian method showed 100% success in assigning Korean and Chinese individual pigs into their correct breeds of origin and 100% exclusion success from all alternative reference populations at P < 0.001. These findings indicate that the Korean native pig has been experiencing progressive interbreeding with Western pig breeds after originating from a North China pig breed with a black coat color. Considering the close genetic relationship of Korean pigs to the Western breeds such as Berkshire and Landrace, our findings can be used as valuable genetic information for the preservation and further genetic improvement of the Korean native pig.

Alleles↗

Atypical manifestations of reversible posterior leukoencephalopathy syndrome: findings on diffusion imaging and ADC mapping.

Typically, reversible posterior leukoencephalopathy syndrome (RPLS) involves the parieto-occipital lobes. When regions of the brain other than the parieto-occipital lobes are predominantly involved, the syndrome can be called atypical RPLS. The purpose of this study is to find radiological and pathophysiological features of atypical RPLS by using diffusion-weighted imaging (D-WI). We retrospectively reviewed seven patients (two with eclampsia, one with cyclosporine neurotoxicity, and four with hypertensive encephalopathy) with atypical MR manifestations of RPLS. Changes in signal intensity on T2-weighted imaging (T2-WI) and D-WI, and ADC ratio, were analyzed. In patients with atypical manifestation of RPLS, high signal intensities on T2-WI were noted in the frontal lobe, basal ganglia, thalamus, brainstem, and subcortical white matter in regions other than the parieto-occipital lobes. These areas of increased signal intensities on T2-WI showed increased ADC values, representing vasogenic edema in all seven patients. This result should be very useful in differentiating atypical RPLS from other metabolic brain disorders that affect the same sites with cytotoxic edema.

Adult↗

Pseudorapidity distribution of charged particles in d+Au collisions at sqrt[sNN]=200 GeV.

The measured pseudorapidity distribution of primary charged particles in minimum-bias d+Au collisions at sqrt[s(NN)]=200 GeV is presented for the first time. This distribution falls off less rapidly in the gold direction as compared to the deuteron direction. The average value of the charged particle pseudorapidity density at midrapidity is |eta|< or =0.6)=9.4+/-0.7(syst) and the integrated primary charged particle multiplicity in the measured region is 82+/-6(syst). Estimates of the total charged particle production, based on extrapolations outside the measured pseudorapidity region, are also presented. The pseudorapidity distribution, normalized to the number of participants in d+Au collisions, is compared to those of Au+Au and p+(-)p systems at the same energy. The d+Au distribution is also compared to the predictions of the parton saturation model, as well as microscopic models.

Journal Article↗

Experimental investigation of the mammary gland tumour phantom for multifrequency microwave radio-thermometers.

Microwave radiometry is a spectral measurement technique for resolving the electromagnetic radiation of matter when its temperature is above absolute zero. The radio-thermometer utilises this technique and consequently can provide temperature distributions in subcutaneous biological tissues. A new phantom was proposed that imitates a mammary gland tumour, and the brightness temperature was observed using radio-thermometers operated at different frequencies, 1.75GHz and 3GHz. The proposed phantom, simulating heat diffusion propagated by tissues around real tumours, revealed that the thermal characteristics of the tumour imitator were well matched to the heat transfer properties of a real tumour and a proportional linear relationship between the location of the tumour imitator and the brightness temperature in a homogenous medium was established. From experiments using the proposed mammary gland tumour phantom and a clinical trial on patients with breast cancer, it could be concluded that a radio-thermometer with a short wavelength (lambda = 10cm, i.e. f= 3GHz) is useful to resolve a thermal anomaly at a shallow depth in an homogenous medium such as a breast.

Adult↗

Genetic analysis of the LKB1/STK11 gene in hepatocellular carcinomas.

The tumour suppressor gene, LKB1/STK11, has been mapped to chromosome 19p13, a region showing frequent allelic loss in various human cancers, including hepatocellular carcinoma (HCC). Additionally, LKB1 physically associates with p53 and regulates p53-dependent apoptotic pathways. To investigate whether genetic alterations of LKB1 could be involved in the tumorigenesis of HCC, we analysed the genetic alterations of the LKB1 and p53 genes in seven dysplastic nodules and 80 HCCs. We found one LKB1 missense mutation, CCG-->CTG (Pro-->Leu) at codon 281 within the kinase domain. We also found allelic loss in six of 27 (22%) informative HCC cases and all of them were HBV-positive cases. In addition, we detected seven missense, one nonsense and one silent mutations (nine of 80, 11%) of p53 in HCCs only. These results suggest that genetic alterations of the LKB1 or p53 genes may play an important role in tumour development or progression of a sub-set of HCCs, and may also provide alternative mechanisms to protect the HCC cell from p53-dependent apoptosis.

AMP-Activated Protein Kinase Kinases↗

Effects of Lactobacilli and an acidophilic fungus on the production performance and immune responses in broiler chickens.

Accumulated lines of evidence indicate that inactivated probiotics could have beneficial effects similar to those of live probiotics. Two strains of disrupted, cobalt-enriched, lactic acid bacteria (Lactobacillus acidophilus and Lactobacillus casei) and a disrupted fungal mycelium (Scytalidium acidophilum) were spray-mixed onto a mash basal feed, in 2 concentrations, prior to pelleting. The effects of these probiotics on production performance and immune response in broiler chickens were investigated. The production parameters, including BW, feed intake (FI), BW gain (BWG), and feed conversion ratio (FCR), were monitored weekly during a 6-wk trial. The immune response was evaluated by immunizing the birds with the antigen keyhole limpet hemocyanin (KLH) followed by a serological assay to measure blood IgA and IgG titers. Some of the production parameters were significantly improved by low L. casei (LCL; for BW and BWG), high L. acidophilus (LAH; for BW and BWG), and high fungal (FH; for BW, BWG, and FI) in comparison with the nonadditive control (NC-). However, these 3 treatments (LCL, LAH, and FH) did not enhance the measured immune responses. Instead, the titers of serum KLH-specific IgA in high L. casei (LCH) and low L. acidophilus (LAL) were significantly higher than those of NC-, 10 d after immunization. None of the probiotic treatments increased the titer of KLH-specific IgG in blood. Our results indicate that disrupted and cobalt-enriched L. acidophilus or L. casei was able to enhance production performance of broiler chickens. The fungal mycelium, S. acidophilum, when used at a high concentration, also demonstrated its potential for the first time to be used as a probiotic. In addition, the optimal concentration for administering probiotics is strain dependent. A higher dose does not always result in a better performance.

Animal Nutritional Physiological Phenomena↗

Synthesis and characterization of thermosensitive chitosan copolymer as a novel biomaterial.

Novel water-soluble thermosensitive chitosan copolymers were prepared by graft polymerization of N-isopropylacrylamide (NIPAAm) onto chitosan using cerium ammonium nitrate (CAN) as an initiator. The physicochemical properties of the resulting chitosan-g-NIPAAm copolymers were characterized by Fourier transform infrared (FT-IR) spectroscopy, 1H-nuclear magnetic resonance, X-ray diffraction measurement, thermogravimetric analysis (TGA) and solubility test. Sol-gel transition behavior was investigated by the cloud point measurement of the chitosan-g-NIPAAm aqueous solution. The gelling temperature was examined using the vial inversion method. The percentage of grafting (%) and efficiency of grafting (%) were investigated according to concentrations of monomer and initiator. The maximum grafted chitosan copolymer was obtained with 0.4 M NIPAAm and 6 x 10(-3) M CAN. Water-soluble chitosan-g-NIPAAm copolymers were prepared successfully and they formed thermally reversible hydrogel, which exhibits a lower critical solution temperature (LCST) around 32 degrees C in aqueous solutions. A preliminary in vitro cell study showed nontoxic and biocompatible properties. These results suggest that chitosan-g-NIPAAm copolymer could be very useful in biomedical and pharmaceutical applications as an injectable material for cell and drug delivery.

Acrylamides↗

Features of the metabolic syndrome after childhood craniopharyngioma.

Obesity and multiple pituitary hormone deficiency are common complications after surgery for childhood craniopharyngioma. We hypothesized that post craniopharyngioma surgery, children are at high risk for the metabolic syndrome, including insulin resistance due to excess weight gain and GH deficiency. This study characterized body composition (anthropometry and dual energy x-ray absorptiometry) and metabolic outcomes in 15 children (10 males and 5 females; age, 12.2 yr; range, 7.2-18.5 yr) after surgical removal of craniopharyngioma. In 9 subjects, outcomes were compared with those of healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Insulin sensitivity was measured by 40-min iv glucose tolerance test. Seventy-three percent of subjects were overweight or obese. Sixty-six percent had normal growth velocity without GH treatment. Subjects had increased abdominal adiposity (P = 0.008) compared with controls. However, there was no significant difference in total body fat. Subjects had higher fasting triglycerides (P = 0.02) and lower high density lipoprotein cholesterol to total cholesterol ratio (P = 0.015). Insulin sensitivity was equally reduced for subjects and controls (P = 0.86). After craniopharyngioma removal, patients had more features of the metabolic syndrome compared with controls. This could be a result of hypothalamic damage causing obesity and GH deficiency. Further studies exploring predictors of the metabolic syndrome after craniopharyngioma surgery are required.

Abdomen↗

Nitrogen removal characteristics analyzed with gas and microbial community in thermophilic aerobic digestion for piggery waste treatment.

In order to characterize the nitrogen conversion characteristics in a thermophilic aerobic digestion (TAD) system, a laboratory study has been conducted with the analysis of effluent gas and microbial community in the sludge samples. The lab TAD system was operated with HRT of 3 days and 60 degrees C. Based on the nitrogen mass balance, it has been found that about 2/3 of the daily load of nitrogen was converted to the gaseous form of nitrogen whereas cellular transformation and unmetabolized nitrogen accounted for about 1/3. Among the gaseous nitrogen transformation, significant amount of influent nitrogen had been converted to N2 gas (29% of influent N) and N2O (9% of influent N). Ammonia conversion was only 28% of influent N. The detection of N2O gas is a clear indication of the biological nitrogen reduction process in the thermophilic aerobic digester. No conclusive evidence for the existence of aerobic deammonification has been found. The microbial community analysis showed that thermophilic bacteria such as Bacillus thermocloacae, Bacillus sp. and Clostridial groups dominated in this TAD reactor. The diverse microbial community in TAD sludge may play an important role in removing both strong organics and nitrogen from piggery waste.

Agriculture↗