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Biomedical subjects

K Choi

Publications and source records attributed to K Choi.

At least 19 recordsLinked to original sources
PubMed2006

Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy.

Transglutaminase 2 (TG2, a.k.a. tissue transglutaminase) belongs to a family of transglutaminase enzymes that stabilize proteins by affecting covalent crosslinking via formation of amide bonds. Cell surface TG2 is directly involved as an adhesive receptor in cell-extracellular matrix (ECM) interactions. Here, we show that TG2 activity is elevated in glioblastomas compared with non-neoplastic brain. Immunofluorescent studies showed increased staining of fibronectin colocalized with TG2 in the ECM in glioblastomas. In addition, small clusters of invading human glioblastoma cells present in non-neoplastic brain parenchyma secrete high levels of TG2 and fibronectin that distinguish them from normal brain stroma. Downregulation of TG2 in U87MG glioblastoma cells with RNAi demonstrated decreased assembly of fibronectin in the ECM. Treatment with KCC009 blocked the remodeling of fibronectin in the ECM in glioblastomas in both in vitro and in vivo studies. KCC009 treatment in mice harboring orthotopic glioblastomas (DBT-FG) sensitized the tumors to N,N'-bis(2-chloroethyl)-N-nitrosourea chemotherapy, as measured by reduced bioluminescence, increased apoptosis and prolonged survival. The ability of KCC009 to interfere with the permissive remodeling of fibronectin in the ECM in glioblastomas suggests a novel target to enhance sensitivity to chemotherapy directed not only at the tumor mass, but also invading glioblastoma cells.

Animals↗
PubMed2006

Parathion degradation and toxicity reduction in solar photocatalysis and photolysis.

The solar photocatalytic degradation of methyl parathion was investigated using a circulating TiO2/solar light reactor. Under solar photocatalysis condition, parathion was more effectively degraded than solar photolysis and TiO2-only conditions. With solar photocatalysis, 20 mg/L of parathion was completely degraded within 60 min with a TOC decrease of 63% after 150 min. The main ionic byproducts during photocatalysis recovered from parathion degradation were mainly as NO3-, NO2- and NH4+, 80% of the sulphur as SO4(2-), and 5% of phosphorus as PO4(3-). The organic intermediates 4-nitrophenol and methyl paraoxon were also identified, and these were further degraded in solar photocatalytic condition. Two different bioassays (Vibrio fischeri and Daphnia magna) were used to test the acute toxicity of solutions treated by solar photocatalysis and photolysis. The Microtox test using V. fischeri showed that the toxicity expressed as EC50 (%) value increased from 5.5% to >82% in solar photocatalysis, indicating that the treated solution is non-toxic, but only increased from 4.9 to 20.5% after 150 min in solar photolysis. The acute toxicity test using D. magna showed that EC50 (%) increased from 0.05 to 1.08% under solar photocatalysis, but only increased to 0.12% after 150 min with solar photolysis, indicating the solution is still toxic. The pattern of toxicity reduction parallels the decrease in TOC and the parathion concentrations.

Aliivibrio fischeri↗
PubMed2006

Comparison of membrane biofouling in nitrification and denitrification for the membrane bioreactor (MBR).

Batch filtration tests were conducted to compare the characteristics of membrane biofouling with regard to nitrification and denitrification. A Modified Fouling Index (MFI) was obtained using a stirred cell tester. The denitrification assays showed higher membrane fouling rates than the nitrification assays. The fouling became worse, not only due to pore blocking resistance, but also from cake layer resistance after denitrification. The Extracellular Polymeric Substances (EPS) concentration and relative hydrophobicity were decreased after denitrification, resulting in floc deterioration. The floc deterioration was assumed to have increased the cake layer resistance in the filtration test. The protein Soluble Microbial Products (SMP) concentration, portion of high molecular weight in carbohydrate SMP and relative hydrophobicity were increased after denitrification, which was assumed to cause membrane pore blocking. The changes in the EPS and SMP characteristics were the main fouling parameters in denitrification.

Biomass↗
PubMed2004

Ubiquitin-proteasome pathway as a primary defender against TRAIL-mediated cell death.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death as well as expression of proinflammatory genes such as CXCL8 in malignant human astrocytoma cells. However, the molecular mechanisms that determine the fate of cells are not yet understood. The ubiquitin (Ub)-proteasome pathway regulates a wide range of cellular functions through degradation of various regulatory proteins; given this, we hypothesized that this pathway may play a central role in TRAIL-mediated signaling. We demonstrate here that inhibition of the Ub-proteasome pathway enhanced TRAIL-mediated cell death of human astrocytoma CRT-MG cells within hours by blocking degradation of active caspase-8 and -3. Proteasome inhibitors suppressed TRAIL-mediated activation of NF-kappaB; however, inhibition of the NF-kappaB pathway alone was not sufficient to enhance TRAIL-mediated cell death. Collectively, these results suggest that the Ub-proteasome pathway may play an important role as an antiapoptotic surveillance system by eliminating activated caspases as well as mediating NF-kappaB-dependent signals.

Apoptosis↗
PubMed2004

A novel synthetic method for nanosized crystalline titania for use in the decomposition of dyes.

Photocatalytically active nanocrystalline titania particles were prepared using a hydrothermal process, by controlling the particle size and crystallinity. The crystalline structures and morphologies of the particles were characterized by X-ray diffraction and transmission electron microscopy. The BET method was used to determine the surface area and verify the grain size. To estimate the photocatalytic activity of the synthesized particles, a dye photodegradation experiment was carried out and the activity of the particles was compared with that of conventional titania. The results show that synthesized nanocrystalline titania particles had a higher photocatalytic activity than that of conventional titania. These findings provide a basis for the preparation of more effective and usef ul materials for use in AOP applications.

Catalysis↗
PubMed2003

Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney.

Glomerulosclerosis is a common morphologic result seen in almost all progressed renal diseases, and is the characteristic change in focal segmental glomerulosclerosis (FSGS). The most convincing hypothesis for glomerulosclerosis is cytokine-mediated injury by infiltrating immune cells in the glomerulus and tubulointerstitial area. This study investigated whether the anti-inflammatory effect of interleukin-10 (IL-10) when expressed by a recombinant adenoviral vector can prevent the onset of glomerulosclerosis in FGS/Kist mice (an animal model with naturally occurring renal failure initiated by FSGS). Each group of mice received recombinant adenoviruses encoding human IL-10 (Ad:hIL-10) by intraparenchymal injection at 6 weeks and were examined for cytokine expression, glomerular sclerotic index, and proteinuria. After injection of Ad:hIL-10 to the kidney, IL-10 expression was found to last over 20 days. Mice treated with Ad:hIL-10 were shown to have a significant reduction in the glomerular sclerotic index at 10 weeks when compared to control groups. The level of proteinuria in Ad:hIL-10-treated mice was also significantly reduced. About 50% of the urine samples of naive and Ad:LacZ-treated groups had severe levels of proteinuria. By contrast, at 10 weeks the group treated with Ad:hIL-10 had lower levels of proteinuria and transforming growth factor-beta1 (TGF-beta1) expression. These results demonstrate that IL-10 effectively prevents the development of glomerulosclerosis in FGS/Kist mice, and IL-10 gene therapy may be of use for the treatment of renal failure.

Adenoviridae↗
PubMed2001

Congestion of right liver graft in living donor liver transplantation.

BACKGROUND: Left liver graft from a small donor will not meet the metabolic demands of a larger adult recipient. One solution to this problem is to use a right liver graft without a middle hepatic vein (MHV). However, the need for drainage from the MHV tributaries has not yet been described. METHODS: Five right liver grafts without a MHV were transplanted in patients including two hepatitis B virus-cirrhosis, two fulminant hepatic failure and one secondary biliary cirrhosis. The graft weight ranged from 650 to 1,000 g, corresponding to 48 to 83% of the standard liver volume of the recipients. RESULTS: Two of five recipients were complicated with severe congestion of the right median sector immediately after reperfusion, followed by prolonged massive ascites and severe liver dysfunction. One of the patients died of sepsis with progressive hepatic dysfunction 20 days after the operation. CONCLUSIONS: Preservation and reconstruction of the MHV tributaries is recommended to prevent congestion of the right liver graft without MHV.

Body Weight↗
PubMed2001

Endogenous glycosylphosphatidylinositol-specific phospholipase C releases renal dipeptidase from kidney proximal tubules in vitro.

Spontaneous enzymic release of renal dipeptidase (RDPase; EC 3.4.13.19), a glycosylphosphatidylinositol (GPI)-linked ectoenzyme, was observed in vitro during incubation of porcine proximal tubules at 37 degrees C. Triton X-114 phase separation of the released RDPase showed that the majority of the enzyme activity partitioned into the aqueous phase, indicating its hydrophilic nature. Immunoblot analyses using an antibody against the cross-reacting determinant (CRD) inositol 1,2-cyclic monophosphate, the epitope formed by phospholipase C (PLC) cleavage of the GPI anchor on a protein, detected the released RDPase. Reprobing the immunoblot with an anti-RDPase serum showed the RDPase band co-migrating with the CRD band. The release of RDPase from the proximal tubules was a Ca(2+)-dependent process and had a pH optimum of 9.0. These results indicate that RDPase is released from the proximal tubules by the action of a distinct endogenous GPI-specific PLC.

Animals↗
PubMed2001

Toxicity evaluation of metal plating wastewater employing the Microtox assay: a comparison with cladocerans and fish.

The relative sensitivity of the Microtox assay is closely related to the type of toxicant, and hence its utility in biomonitoring effluents is better evaluated on a case-by-case basis. The Microtox assay, employing the marine bacterium Vibrio fischeri, was evaluated for its applicability in monitoring metal plating wastewater for toxicity. The results of the Microtox assay after 5, 15, and 30 min of exposure, were compared with data obtained from conventional whole effluent toxicity testing (WET) methods that employed Daphnia magna, Ceriodaphnia dubia, and the fathead minnow (Pimephales promelas). The Microtox assay produced notably comparable EC50 values to the LC50 values of the acute fathead minnow toxicity test (< 0.5 order of difference). The Spearman's rank correlation analyses showed that the bacterial assay, regardless of exposure duration, correlated better with the acute fish than the daphnid results (p < 0.05). These observations were consistent to other studies conducted with inorganic contaminants. The relative sensitivity of the 30-min Microtox assay was within the range of the two frequently used acute daphnid/fish toxicity tests. In conclusion, the Microtox assay correlated well with the acute fathead minnow data and is well suited for toxicity monitoring for these types of industrial wastes.

Animals↗
PubMed2001

Calreticulin, a calcium-binding molecular chaperone, is required for stress response and fertility in Caenorhabditis elegans.

Calreticulin (CRT), a Ca(2+)-binding protein known to have many cellular functions, including regulation of Ca(2+) homoeostasis and chaperone activity, is essential for heart and brain development during embryogenesis in mice. Here, we report the functional characterization of Caenorhabditis elegans calreticulin (crt-1). A crt-1 null mutant does not result in embryonic lethality but shows temperature-dependent reproduction defects. In C. elegans CRT-1 is expressed in the intestine, pharynx, body-wall muscles, head neurons, coelomocytes, and in sperm. crt-1 males exhibit reduced mating efficiency and defects late in sperm development in addition to defects in oocyte development and/or somatic gonad function in hermaphrodites. Furthermore, crt-1 and itr-1 (inositol triphosphate receptor) together are required for normal behavioral rhythms. crt-1 transcript level is elevated under stress conditions, suggesting that CRT-1 may be important for stress-induced chaperoning function in C. elegans.

Animals↗
PubMed2000

Target site search and effective inhibition of leukaemic cell growth by a covalently closed multiple anti-sense oligonucleotide to c-myb.

Systematic secondary structure simulation of a target mRNA sequence is shown to be effective for locating a good anti-sense target site. Multiple selected anti-sense sequences were placed in a single molecule. The anti-sense oligonucleotide (oligo) was covalently closed to avoid exonuclease activities and was designated CMAS (covalently closed multiple anti-sense)-oligo. CMAS-oligo was found to be stable, largely preserving its structural integrity after 24 h of incubation in the presence of either exonuclease III or serum. When human c-myb mRNA was targeted by the c-myb CMAS-oligo, expression of the gene was completely abolished. Further, tumour cell growth was inhibited by 82+/-3% as determined by an MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and by 90+/-1% by [(3)H]thymidine incorporation. When a leukaemic cell line K562 was treated with CMAS-oligo, colony formation on soft agarose was also decreased by 93%. In contrast, treatment with a scrambled control oligo did not significantly inhibit leukaemic cell growth. These results suggest that a rational target site search is possible for an anti-sense oligo and that CMAS-oligo can be employed as an effective anti-sense agent with enhanced stability.

Cell Division↗
PubMed2000

Potent growth inhibition of leukemic cells by novel ribbon-type antisense oligonucleotides to c-myb1.

We studied the effects of antisense oligonucleotides (AS oligos) with a novel structure. The AS oligos were covalently closed to avoid exonuclease activities by enzymatic ligation of two identical molecules. The AS oligos of a ribbon type (RiAS oligos) consist of two loops containing multiple antisense sequences and a stem connecting the two loops. Three antisense sequences targeting different binding sites were placed in a loop that was designed to form a minimal secondary structure by itself. RiAS oligos were found to be stable because they largely preserved their structural integrity after 24 h incubation in the presence of either exonuclease III or serums. When a human promyelocytic cell line, HL-60, was treated with RiAS oligos to c-myb, c-myb expression was effectively ablated. Cell growth was inhibited by >90% determined by both the 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and [(3)H]thymidine incorporation. Further, when the leukemic cell line K562 was treated with c-myb RiAS oligos, colony formation on soft agarose was reduced by 92 +/- 2%. These results suggest that RiAS oligos may be employed for developing molecular antisense drugs as well as for the functional study of a gene.

Base Sequence↗
PubMed2000

Acute and chronic life cycle toxicity of acenaphthene and 2,4,6-trichlorophenol to the midge Paratanytarsus parthenogeneticus (Diptera: Chironomidae).

The acute and life cycle toxicities of acenaphthene and 2,4,6-trichlorophenol (2,4,6-TCP) were evaluated using the parthenogenic dipteran larva, Paratanytarsus parthenogeneticus, of the family Chironomidae. Static 48 h acute toxicity tests employed third instar larvae, and the flow-through 20-day life cycle tests were initiated with eggs. No acute lethal effect was observed in the saturated concentration (2.1 mg/l) of acenaphthene in water, and the median lethal concentration of 2,4,6-TCP was approximately 40 mg/l. In the life cycle toxicity test with acenaphthene, hatchability of the midge was affected by 50% at an exposure concentration of approximately 0.17 mg/l. The median effective concentration for larval, pupal and adult development was found between 0.06 and 0.07 mg/l, respectively, and these were significantly lower than the effective concentration for hatching success. With regard to 2,4,6-TCP toxicity, the median effective concentration for midge hatchability was 4.23 mg/l. The larval development, pupal formation and adult emergence, however were impeded at 1.60, 1.46 and 1.33 mg/l, respectively. Each level was noticeably lower than the median effective concentration for hatchability. The concentrations for each compound that interfered with the development to fourth instar, pupa and adult were not significantly different. These results indicate that larval developments after hatching were the most sensitive stages and affected the success of midge growth.

Acenaphthenes↗
PubMed2000

Calreticulin couples calcium release and calcium influx in integrin-mediated calcium signaling.

The engagement of integrin alpha7 in E63 skeletal muscle cells by laminin or anti-alpha7 antibodies triggered transient elevations in the intracellular free Ca(2+) concentration that resulted from both inositol triphosphate-evoked Ca(2+) release from intracellular stores and extracellular Ca(2+) influx through voltage-gated, L-type Ca(2+) channels. The extracellular domain of integrin alpha7 was found to associate with both ectocalreticulin and dihydropyridine receptor on the cell surface. Calreticulin appears to also associate with cytoplasmic domain of integrin alpha7 in a manner highly dependent on the cytosolic Ca(2+) concentration. It appeared that intracellular Ca(2+) release was a prerequisite for Ca(2+) influx and that calreticulin associated with the integrin cytoplasmic domain mediated the coupling of between the Ca(2+) release and Ca(2+) influx. These findings suggest that calreticulin serves as a cytosolic activator of integrin and a signal transducer between integrins and Ca(2+) channels on the cell surface.

Animals↗
PubMed2000

Grass carp (Ctenopharyngodon idellus) bile may inhibit the release of renal dipeptidase from the proximal tubules by nitric oxide generation.

There are many reports on acute renal failure (ARF) after ingestion of grass carp bile (CB; Ctenopharyngodon idellus). Renal dipeptidase (RDPase; EC 3.4.13.19) is a glycosylphosphatidylinositol-anchored ectoenzyme within the renal proximal tubules (PTs) and is proposed as a diagnostic enzyme of renal disease. We examined the release of RDPase following treatment with CB and various nitric oxide (NO) related compounds in porcine PTs. The RDPase release from PTs was inhibited by CB in a concentration-dependent manner and was also inhibited by sodium nitroprusside (direct NO donor) and L-arginine (NO synthase substrate) in the tested range (0-12 mM). CB-treated (0. 1 mg/ml) PTs showed a decreased RDPase activity in comparison with the control group. This inhibition was blocked by 2 mM L-NAME (NO synthase inhibitor) and U73122 (inhibitor of phosphatidylinositol-specific phospholipase C) in a concentration-dependent manner. Eel bile (0-0.1 mg/ml), used as the control, did not significantly affect the RDPase release from PTs. The NO concentration was observed as nitrite, the degradation product of the NO metabolism, increased in proportion to CB and L-arginine. The increase of nitrite to 151.5% by CB treatment (0.1 mg/ml) was blocked by 2 mM L-NAME (95.5%). When the phospholipase C pathway was blocked by 10 and 20 microM U73122, the nitrite generation decreased to 122.7 and 89.4%, respectively. These results strongly suggest that NO generation and the phospholipase C pathway affect the RDPase release from the PTs and that they may be involved in the development of ARF in vivo following CB ingestion. The release of RDPase from PTs could be a useful tool not only for this CB-caused ARF, but also for the elucidation of other biochemical mechanisms.

Animals↗