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Biomedical subjects

J W Park

Publications and source records attributed to J W Park.

At least 19 recordsLinked to original sources

Enhanced production of Scenedesmus spp. (green microalgae) using a new medium containing fermented swine wastewater.

Fermented swine urine (3%) (v/v) was added to a control medium (CT), named KEP I, and an aquatic microalgal culture (10% Bold's Basal Medium) for growing mixed Scenedesmus species. During a two-month period, the KEP I medium effected, the delayed onset of the stationary phase of cell division in a batch culture. After 31 days, of culturing, the growth rate (3-fold), dry weight (2.6-fold) and amino acid levels (2.7-fold), and secondary metabolites including chlorophyll a (2.1-fold), astaxanthin (2.8-fold), lutein (2.7-fold) and alpha (greater than 30-fold) and beta-carotene (greater than 5-fold) increased a greater degree in Scenedesmus grown in KEP I medium than in CT medium. Total lipids were much less in cells grown in KEP I than those grown in CT. An increased quantum yield of photosystem II of the aquatic microalgae. The KEP I medium should improve the cost efficiency of industrial mass batch cultures for CO(2) sequestration, bioremediation, phytonutrients, agricultural fertilizers, and microalgal stock for the species preservation of aquaculture strains for use in young fish feed. It may also serve to attenuate negative environmental impact via the recycling of animal wastewater.

Animals↗

Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations.

Isolated oral clefts, including cleft lip with/without cleft palate (CL/P) and cleft palate (CP), have a complex and heterogeneous etiology. Case-parent trios from three populations were used to study genes spanning chromosome 2, where single nucleotide polymorphic (SNP) markers were analyzed individually and as haplotypes. Case-parent trios from three populations (74 from Maryland, 64 from Singapore and 95 from Taiwan) were genotyped for 962 SNPs in 104 genes on chromosome 2, including two well-recognized candidate genes: TGFA and SATB2. Individual SNPs and haplotypes (in sliding windows of 2-5 SNPs) were used to test for linkage and disequilibrium separately in CL/P and CP trios. A novel candidate gene (ZNF533) showed consistent evidence of linkage and disequilibrium in all three populations for both CL/P and CP. SNPs in key regions of ZNF533 showed considerable variability in estimated genotypic odds ratios and their significance, suggesting allelic heterogeneity. Haplotype frequencies for regions of ZNF533 were estimated and used to partition genetic variance into among-and within-population components. Wright's fixation index, a measure of genetic diversity, showed little difference between Singapore and Taiwan compared with Maryland. The tensin-1 gene (TNS1) also showed evidence of linkage and disequilibrium among both CL/P and CP trios in all three populations, albeit at a lower level of significance. Additional genes (VAX2, GLI2, ZHFX1B on 2p; WNT6-WNT10A and COL4A3-COL4A4 on 2q) showed consistent evidence of linkage and disequilibrium only among CL/P trios in all three populations, and TGFA showed significant evidence in two of three populations.

Chromosome Mapping↗

Assembly of nucleic acid-lipid nanoparticles from aqueous-organic monophases.

Effective, reproducible, and scalable methods for DNA-lipid assembly are important for the success of non-viral vectors in in vivo gene therapy. We hypothesized DNA-lipid assembly would be optimal if started from a liquid monophase where both DNA and lipids separately form molecular or micellar solutions prior to mixing, without preexisting condensed lipid phases, thus allowing DNA-lipid assembly under conditions close to equilibrium. Previously, we found that mixing plasmid DNA, 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC), cholesterol and a cationic lipid, 1, 2-dioleoyl-3-(trimethylammonio) propane (DOTAP) in 50% (v/v) aqueous ethanol spontaneously produced an optically transparent solution. Upon ethanol removal, DNA-lipid nanoparticles (Genospheres) were formed. For comparison with well-known technologies, different DNA-lipid particles were prepared by interaction of plasmid DNA and stable or ethanol-destabilized lipid vesicles by combining the components in water or 30% (v/v) aqueous ethanol, respectively. Among the three studied DNA-lipid assembly methods, only Genospheres combined the properties of small size (less than or around 100 nm), high incorporation of both lipid and DNA, high degree of DNA protection (dye accessibility 5-12%), a narrow distribution of particle density and when immuno-targeted, the highest transfection efficiency in HER2-overexpressing cells in vitro. We conclude that the Genosphere assembly methodology offers advantages for the development of effective, scalable and targetable non-viral gene delivery vectors.

Base Sequence↗

High throughput SNP and expression analyses of candidate genes for non-syndromic oral clefts.

BACKGROUND: Recent work suggests that multiple genes and several environmental risk factors influence risk for non-syndromic oral clefts, one of the most common birth defects in humans. Advances in high-throughput genotyping technology now make it possible to test multiple markers in many candidate genes simultaneously. METHODS: We present findings from family based association tests of single nucleotide polymorphism (SNP) markers in 64 candidate genes genotyped using the BeadArray approach in 58 case-parent trios from Maryland (USA) to illustrate how multiple markers in multiple genes can be analysed. To assess whether these genes were expressed in human craniofacial structures relevant to palate and lip development, we also analysed data from the Craniofacial and Oral Gene Expression Network (COGENE) consortium, and searched public databases for expression profiles of these genes. RESULTS: Thirteen candidate genes showed significant evidence of linkage in the presence of disequilibrium, and ten of these were found to be expressed in relevant embryonic tissues: SP100, MLPH, HDAC4, LEF1, C6orf105, CD44, ALX4, ZNF202, CRHR1, and MAPT. Three other genes showing statistical evidence (ADH1C, SCN3B, and IMP5) were not expressed in the embryonic tissues examined here. CONCLUSIONS: This approach demonstrates how statistical evidence on large numbers of SNP markers typed in case-parent trios can be combined with expression data to identify candidate genes for complex disorders. Many of the genes reported here have not been previously studied as candidates for oral clefts and warrant further investigation.

Chromosome Mapping↗

Outcome of patients with recurrent hepatocellular carcinoma in liver transplantation.

Liver transplantation (OLT) is the treatment of choice for patients with hepatic cirrhosis related hepatocellular carcinoma (HCC). Among 156 liver transplant patients for HCC from June 1996 to February 2005, 23 had recurrent HCC. To evaluate risk factors that affect early recurrence of HCC after OLT, we divided the 23 patients into two groups: early (< or =12 months) and late (>12 months) recurrences. Among them, 15 patients were dead and eight alive patients had been followed to 31 July 2005. The most common recurrence site was the grafted liver (n = 15), next was bone (n = 11), lung (n = 8), lymph node (n = 6), brain (n = 4), skin (n = 2), adrenal gland (n = 1). There were no significant differences between the two groups in age or tumor size, number of tumors, cell differentiation, alpha-feto protein levels, tumor staging, number of patients within Milan criteria, steroid pulse therapy, infectious diseases, and immunostaining of tumor. In our study, there were no risk factors that predict early tumor recurrence. We noticed that more patients in the early recurrence group were excluded by Milan criteria due to a more progressed tumor staging with higher mean levels of serum alpha-feto protein.

Adult↗

Prognosis after liver transplantation predicted by preoperative MELD score.

The model for end-stage liver disease (MELD) has been an excellent predictor of 3-month mortality among cirrhotic patients awaiting orthotopic liver transplantation (OLT). The aim of this study was to evaluate whether the preoperative MELD score predicts short-term prognosis after OLT. We enrolled 98 adult liver transplant patients performed at our center from January 2001 to December 2002. In univariate analysis of risk factors for death within 3 and 6 months after liver transplantation, serum total bilirubin, creatinine, MELD score, hyponatremia with ascites, Child-Turcotte-Pugh (CTP) score were statistically significant parameters (P < .05). By logistic regression, none of the risk factors were subjected to multivariate analysis showed statistical significance. The odds ratios of the MELD score, hyponatremia with ascites, CTP score within 3 months were 0.997, 1.151, and 0.726 with 95% confidence intervals of [0.899, 1.105], [0.102, 12.959], and [0.389, 1.352], respectively. The odds ratio of MELD score, hyponatremia with ascites, CTP score within 6 months were 0.996, 0.914, and 0.764, with 95% confidence intervals of [0.901, 1.102], [0.089, 9.369], and [0.417, 1.401], respectively. Although MELD score has been a good predictor of short-term prognosis before OLT, MELD did not show an influence on the short-term prognosis after liver transplantation in this study.

Analysis of Variance↗

Outcomes of hepatitis B virus recurrence after liver transplantation.

The introduction of high doses of hepatitis B immune globulin (HBIG) and lamivudine for liver transplantation (OLT) prophylaxis has reduced the risk of hepatitis B recurrence and improved the survival of patients transplanted for hepatitis B virus (HBV)-related liver disease. But, posttransplant prophylaxis strategies to treat the recurrence of HBV have not yet been standardized. We analyzed 23 patients with HBV recurrence among 340 HBV-associated liver transplants performed from September 1996 to April 2004 (6.7%). Nine patients underwent deceased donor OLT and 14, living donor OLT. Mean follow-up was 37 months. Seroconversion after recurrence was observed in 6 of 23 patients (26%). Mean time to HBV recurrence tended to be shorter among the seroconversion (+) patients compared to seroconversion (-) patients (10 months vs 19.7 months; P = .062). Seroconversion rate after HBIG and lamivudine combination therapy for patients with HBV recurrence was 37.5% and time to seroconversion after HBV recurrence was 1.7 months. Seroconversion was best achieved when the pretransplant HBV DNA level was high and HBeAg was positive. Also, seroconversion rate was increased when HBV DNA level was low and the alanine transferase level high at the time of recurrence and when the time to recurrence after transplantation was short. Seroconversion after HBV recurrence, which was observed in 26%, may be increased in selected cases. Accordingly, aggressive treatment should be undertaken after HBV recurrence.

Antiviral Agents↗

Liver transplantation for hepatocellular carcinoma with bile duct thrombi.

In a few cases of hepatocellular carcinoma (HCC), jaundice results from obstructive causes, including tumor invasion or thrombi in the bile duct. We have reported herein our experience with liver transplantation (OLT) for HCC cares showing bile duct thrombi (BDT). From September 1996 to August 2004, 140 adult patients underwent OLT for HCC at our center. Four patients (2.9%) who had OLT performed for HCC had BDT and were included in this study. The patients were all men of mean age 57.0 years. The initial total bilirubin levels were in the range of 2.0 to 30.5 mg/dL. The sizes of the tumors ranged from 2.0 cm to 3.0 cm in diameter, all were single lesions. The median follow-up period was 20.6 months (range: 17.6 to 28.1 months). The only case in which the BDT was identified intraoperatively died 20 months after OLT due to multiple intrahepatic recurrences. The other three patients were alive, showing no evidence of recurrence at the end of follow-up. Although a series of four is too small to reach any conclusion, we suggest that OLT may be a treatment option for HCC with BDT in selected cases.

Adult↗

Safety of donors with fatty liver in liver transplantation.

Steatotic liver graft transplantation affect donor safety as well as recipient survival. We investigated safety of donors according to the extent of fatty change. We retrospectively reviewed donors who underwent right hepatectomy from September 1999 to April 2005, dividing them into three groups according to degree of macrovesicular fatty change upon intraoperative liver biopsy. Group 1 included patients with macrovesicular steatosis of 0 approximately 9%: group 2, 10 approximately 19% and group 3, at least 20%. Two hundred forty-five donors were enrolled with a male to female ratio of 2.02:1 and mean age of 31.8 years. There were 163 donors in group 1, 75 in group 2, and seven in group 3. There was no statistically significant difference in body mass index, operative time, blood loss, postoperative peak serum bilirubin, and aspartate transaminase levels among groups 1, 2, and 3. Overall complication rate, including reoperation, biliary stricture, wound infection, ileus, transfusion, bile leak and fluid collection were not different between the groups. Postoperative hospital stay was also not different. Peak alanine transaminase level was different between each group, and prothrombin time between group 1 and 3, but days until return to normal levels in all measured laboratory parameters were not different. Residual liver volume percent was significantly smaller among group 1 compared to others. In conclusion, fatty livers with less than 30% macrovesicular steatosis may be good donor candidates without significant complications as long as sufficient residual liver volume is left for the donor.

Adolescent↗

Genospheres: self-assembling nucleic acid-lipid nanoparticles suitable for targeted gene delivery.

We describe the assembly of a cationic lipid-nucleic acid nanoparticle from a liquid monophase containing water and a water miscible organic solvent where both lipid and DNA components are separately soluble prior to their combination. Upon removal of the organic solvent, stable and homogenously sized (70-100 nm) lipid-nucleic acid nanoparticles (Genospheres) were formed. The low accessibility (<15%) of the nanoparticle-encapsulated DNA to a DNA intercalating dye indicated well-protected nucleic acids and high DNA incorporation efficiencies. It was demonstrated that Genospheres could be stably stored under a variety of conditions including a lyophilized state where no appreciable increase in particle size or DNA accessibility was observed following reconstitution. Finally, Genospheres were made target-specific by insertion of an antibody-lipopolymer (anti-HER2 scFv (F5)-PEG-DSPE) conjugate into the particle. The target specificity (>100-fold) in HER2 overexpressing SK-BR-3 breast cancer cells was dependent on the degree of PEGylation, where the incorporation of high amounts of PEG-lipid on the particle surface (up to 5 mol%) had only a minor effect on the transfection activity of the targeted Genospheres. In summary, this work describes a novel, readily scalable method for preparing highly stable immunotargeted nucleic acid delivery vehicles capable of achieving a high degree of specific transfection activity.

DNA↗

Zero valent iron and clay mixtures for removal of trichloroethylene, chromium(VI), and nitrate.

A series of batch experiments on free swell, hydraulic conductivity, and contaminant removal efficiency was performed for the combination of bentonite and zero valent iron (ZVI), in order to identify the optimal mixing ratio between bentonite and ZVI. The swell volume of the bentonite-ZVI mixtures did not change with increasing ZVI, and the hydraulic conductivity decreased as the ZVI increased. The reduction rates and removal efficiencies of trichloroethylene (TCE), Chromium(VI), and nitrate increased as ZVI content increased, while there was no practical difference in removal efficiencies between 30% and 100% of ZVI weight contents. Therefore, 30% of the ZVI content was used as the optimal amount in this research since the physical properties, such as swell volume and hydraulic conductivity, as well as the contaminant sorption and reduction were the most efficient. From Raman spectrophotometer analysis, peaks of magnetite, maghemite, and hematite were observed on the surfaces of the bentonites that had been used for the mixtures. Since iron oxides are strong adsorbers of contaminants and magnetites can facilitate the electron transfer of irons, these formations are beneficial for the long-term performance of the iron metals.

Bentonite↗

Residual stress in composites with the thin-ring-slitting approach.

During polymerization, dental composites develop residual stresses that may compromise the marginal integrity and properties of the restorative. The objective of this study was to use the thin-walled ring-slitting method to measure and compare residual stresses. The hypotheses to be tested were that composites would generate different levels of residual stress based on their specific formulations and slitting times. Rings made from composites (Z100, Herculite, and Heliomolar) were cut at different times (10 min, 1 and 24 hrs) after being light-cured, and stress was measured. Residual stress was higher at the earlier cutting times, except for Heliomolar (alpha < 0.05). For the 10-minute and one-hour cutting groups, stress followed this order: Z100 > Herculite > Heliomolar. Early slitting was better to capture residual stress, and the thin-walled rings showed higher values than thick-walled rings and were better able to discriminate residual stress in composites.

Acrylic Resins↗

New antibody immobilization method via functional liposome layer for specific protein assays.

A specific protein assay system based on functional liposome-modified gold electrodes has been demonstrated. To fabricate such assay system, a liposome layer was initially grown on top of a gold layer. The liposome layer contained two kinds of functional molecules: biotin molecules for the binding sites of streptavidin and N-(10,12-pentacosadiynoic)-acetylferrocene molecules for the facile redox probe in electrochemical detections. Then, streptavidin was attached on the functional liposme-modified layer using the interaction of streptavidin-sbiotin complex. On the streptavidin-attached surface, antibody molecules, anti-human serum albumin antibodies could be immobilized without any secondary antibodies. AFM imaging of the streptavidin-attached liposome surface revealed a uniform distribution of closely packed streptavidin molecules. In situ quartz-crystal microbalance and electrochemical measurements demonstrated that the wanted antibody-antigen reactions should occur with high specificity and selectivity. Our specific antibody assay system, based on a functional liposome modified electrode, can be developed further to yield sophisticated structures for numerous protein chips and immunoassay sensors.

Antibodies↗

Intracerebral hemorrhage induces edema and oxidative stress and alters N-methyl-D-aspartate receptor subunits expression.

Intracerebral hemorrhage (ICH) induces brain edema formation via a variety of mechanisms including toxicity due to thrombin and erythrocyte lysis. However, the roles of oxidative damage and excitotoxicity have not been fully elucidated and they are examined in this rat ICH study. Adult male Sprague-Dawley rats received an intracaudate injection of 100 microl autologous whole blood and 5 U of thrombin. Rats were sacrificed at 1 hour, 1 and 3 days, and then the brains processed using Western blotting to quantify N-methyl-D-aspartate receptor (NR) subunit expression. At 3 days, animals were also sacrificed for assessment of protein oxidation using Western blot analysis for dinitrophenyl (DNP) and brain water content. Compared to the contralateral side, ipsilateral basal ganglia NR1 and NR2A subunit expression transiently increased at 1 hour after ICH and thrombin injection. From 24 hours there was a marked down-regulation. At 3 days, marked edema and DNP up-regulation were observed in ICH and thrombin injection groups. The present NR expression up-regulation at 1 hour may reflect the acute cell response after ICH. The down-regulation of NR subunits and upregulation of DNP may be associated with cell damage, towards which thrombin may contribute.

Animals↗

Genotypic resistance of hepatitis B virus to lamivudine in renal transplant recipients.

Renal recipients with hepatitis B virus (HBV) should be treated with prolonged lamivudine. However, lamivudine resistance usually results after YMDD mutation within the HBV polymerase gene. Thereupon, the aim of this study was to investigate the genotypic resistance to lamivudine among renal transplant recipients to identify its effect on the clinical course of HBV in these patients. Between March 1997 and September 2003, eight of 17 renal transplant patients with hepatitis B virus were enrolled into this study and treated with 100 mg of lamivudine once each day. We amplified a selected region of the polymerase gene of HBV in order to confirm mutations in the YMDD motif. Mutations of YMDD region were observed in five of eight patients (62.5%). Out of five patients positive for HBV DNA, three (60%) showed genotypic resistance (YMDD mutation) with a normal ALT level. Two patients converted to HBV DNA negative. But, they were not associated with HBeAg seroconversion. Out of three patients who were pretransplant HBV DNA negative, genotypic resistance was observed in two patients (67%) revealing both positivity of HBe antibody and negativity of HBV DNA. In conclusion, although a normal ALT level and HBV DNA negative are maintained, the mutation of the YMDD locus may develop. Accordingly, we suggest that if the YMDD mutation is not involved in the progression of hepatitis B, lamivudine therapy should be continued despite genotypic resistance.

Adult↗

Phenotype severity and genetic variation at the disease locus: an investigation of nail dysplasia in the nail patella syndrome.

The genetic bases underlying the range and severity of phenotypes in Mendelian disorders is poorly understood; however, improvements in this area have the potential to facilitate analysis of oligogenic disorders. The nail dysplasia observed in Nail Patella Syndrome (NPS) was selected as a quantifiable variable within a Mendelian disorder, for which data could be readily obtained, to allow investigation of the genetic basis of variation. Analysis of SNP haplotypes across the LMX1B gene demonstrated association between the haplotype of the mutant allele and the variability in the nail score (p = 0.024). These results are in contrast to those obtained previously, which supported a modifying role for the wild-type allele. Since there is no evidence that particular mutations, or classes of mutation, are associated with the variation (p > 0.5), further work is required to identify the elements associated with the LMX1B gene that mediate phenotypic severity.

DNA Mutational Analysis↗

Black shale as a sorbent for trichloroethylene and Cr(VI).

Black shale was examined as a natural sorbent for organic and inorganic contaminants. Trichloroethylene (TCE) could be removed well from the water by sorption onto the locally available black shale because of the high organic carbon content (5.2%) of the black shale in this study. Hexavalent chromium Cr(VI) was mainly removed by ionic sorption and reduction in batch and column experiments. Amphiphilic humic acid was also sorbed onto the black shale and could facilitate the sorption of TCE at the same time. Humic acid also enhanced the removal of Cr(VI) by reduction and sorption, but the amount of Cr(VI) adsorbed (mg kg(-1)) was smaller than that of TCE. Considering that the black shale in this study was used without any modifications and has a small surface area, black shale can be a cost-effective natural geosorbent and additive to remove organic contaminants and heavy metals.

Adsorption↗