Biomedical subjects

Y Choi

Publications and source records attributed to Y Choi.

At least 127 records · Page 7Linked to original sources

PubMed2001

The role of peripheral N-methyl-D-aspartate receptors in Freund's complete adjuvant induced mechanical hyperalgesia in rats.

We investigated the role of excitatory amino acid receptors in mechanical hyperalgesia induced by subcutaneous injection of Freund's complete adjuvant (FCA) into the rat hind paw. In normal rats, an intraplantar (i.pl.) injection of L-glutamate, but not of D-glutamate (3 pmol/0.1 ml each) produced a mechanical hyperalgesia in the hind paw with a lowered paw-withdrawal threshold to pressure. In rats that developed mechanical hyperalgesia associated with inflammation in the hind paw following i.pl. injection of FCA (0.15 ml), the injection of N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (1 pmol/0.1 ml) into the inflamed paw increased the paw pressure threshold. On the other hand, the injection of non-NMDA receptor antagonist, 6-cyano-7-nitroqiunoxaline-2,3-dione (CNQX, 10 pmol/0.1 ml) into the inflamed paw had no effect on FCA-induced lowering of the paw pressure threshold. The results suggest that NMDA, but not non-NMDA receptors play a substantial role in mediating the development of mechanical hyperalgesia induced in the inflamed paw following i.pl. FCA injection.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2001

Three pairs of cysteine residues mediate both redox and zn2+ modulation of the nmda receptor.

NMDA receptor activity is modulated by various compounds, including sulfhydryl redox agents and Zn(2+). In addition to a slow and persistent component of redox modulation common to all NMDA receptors, NR1/NR2A receptors uniquely have a rapid and reversible component that has been variously attributed to redox or Zn(2+) effects. Here we show that this rapid modulatory effect can be described by two time constants with relatively fast ( approximately 6 sec) and intermediate (60 sec) half lives, and it is likely to be attributable to both redox agents and Zn(2+). Using site-directed mutagenesis, we identified three pairs of cysteine residues that underlie the various kinetic components of redox modulation of NMDA-evoked currents in Xenopus oocytes expressing NR1/NR2A receptors: (1) Cys 87 and Cys 320 in NR2A underlie the fast component, (2) Cys 79 and Cys 308 in NR1 underlie the intermediate component, and (3) Cys 744 and Cys 798 in NR1 underlie the persistent component. Mutation of these redox-sensitive cysteine residues also affects high-affinity, voltage-independent Zn(2+) inhibition that is specific to NR1/NR2A receptors. Exposure to methanethiosulfonate agents that modify cysteine residues did not block the Zn(2+) inhibition. Thus, these cysteine residues do not appear to coordinate Zn(2+) directly. Instead, the redox status of these cysteine residues may modulate the sensitivity of the receptor to Zn(2+).

Animals↗

PubMed2001

Osteoclastogenesis is enhanced by activated B cells but suppressed by activated CD8(+) T cells.

Host immune response is known to contribute to the progression of periodontitis, and alveolar bone destruction in periodontitis is associated with enhanced osteoclast activity. Therefore, we evaluated the roles of activated lymphocyte subsets in osteoclastogenesis. Osteoclast precursors were co-cultured with activated lymphocytes (B, CD4(+) T, CD8(+) T) in the presence of either macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus soluble receptor activator of NF-kappaB ligand (sRANKL), and subsequent differentiation into active osteoclasts was evaluated by a resorption assay. The activated B and CD4(+) cells, but not CD8(+) T cells, induced osteoclast differentiation in the presence of M-CSF alone. In the presence of M-CSF and sRANKL, B cells induced the formation of small but highly active osteoclasts and increased resorption, while CD8(+) T cells profoundly suppressed osteoclastogenesis. Co-culture using an insert well or supernatant suggested that both B and CD8(+) T cells acted on osteoclasts mostly via soluble proteins. Activated B cells expressed many osteoclastogenic factors including RANKL, TNF-alpha, IL-6, MIP-1alpha, and MCP-3. CD8(+) T cells expressed a substantial amount of osteoprotegerin (OPG) along with RANKL. However, blocking antibody to OPG did not reverse the suppression by CD8(+) T cells, suggesting that other factor(s) are involved. Taken together, activated B cells promoted osteoclastogenesis, while CD8(+) T cells inhibited the osteoclast formation via direct interaction. The results imply the importance of lymphocyte subpopulations in the development of periodontitis.

Animals↗

PubMed2001

Effect of interferon-gamma on the susceptibility to Fas (CD95/APO-1)-mediated cell death in human hepatoma cells.

Many tumors, including hepatocellular carcinomas (HCCs), resist Fas-mediated cell death, which is one of the effector mechanisms in the host's anti-tumor response; however, this resistance can be abolished by interferon-gamma (IFN-gamma). IFN-gamma may sensitize Fas-mediated cell death in several ways, but the exact mechanism in HCCs is uncertain. In this study, we thoroughly investigated the effect of IFN-gamma on the susceptibility of one human normal liver cell line and 12 HCC cell lines to Fas-mediated cell death. We also investigated the effect of IFN-gamma on the expression of various apoptosis-related genes such as the Fas/TNF-related genes, the bcl-2 family, and the caspase family of genes. Although most cell lines showed considerable constitutive expression of Fas, all tested cell lines resisted Fas-mediated cell death without IFN-gamma. When cells were pretreated with IFN-gamma, only three cell lines were made significantly susceptible to Fas-mediated cell death (SNU-354, SNU-387 and SNU-423); the other 10 cell lines were not affected. IFN-gamma increased the mRNA expression of Fas, TRAIL and caspase-1, and surface Fas was also increased. The strongly sensitized cell lines (SNU-354, SNU-387 and SNU-423) showed a particularly potent increment in surface Fas after IFN-gamma treatment (increase in surface Fas > 1.7-fold). This result enabled us to conclude that a potent increment of surface Fas expression is a major sensitizing mechanism of IFN-gamma. We conclude that IFN-gamma cannot play a sensitizing role in most HCC cell lines and that IFN-gamma makes HCC cells susceptible to Fas-mediated cell death through a marked up-regulation of surface Fas in some HCC cells.

Apoptosis↗

PubMed2001

Ifosfamide nephrotoxicity in pediatric cancer patients.

The renal functions in pediatric cancer patients who received ifosfamide (IFO) treatment were evaluated and the risk factors related to IFO nephrotoxicity were determined. The medical records of all children treated with IFO were reviewed, and 62 with normal renal function before IFO treatment were selected. Nephrotoxicity was diagnosed by measuring urine beta2-microglobulin and glucose, and serum phosphate, bicarbonate, and creatinine. Forty-eight (77.4%) had a history of previous cisplatin treatment. Nephrotoxicity was detected in 20 patients (32.3%). beta2-Microglobulinuria was observed in all 20, hypophosphatemia in 10 (16.1%), hypocarbia in 2 (3.2%), glucosuria in 5 (8.1%), and decreased creatinine clearance in 7 (11.3%). The cumulative dose of IFO and a history of previous cisplatin therapy were related to nephrotoxicity. Among the 20 patients with nephrotoxicity, the median cumulative dose of IFO in patients with a low (<500 mg/m2) and high (>500 mg/m2) cumulative dose of previous cisplatin was 80 g/m2 (73-102 g/m2) and 45 g/m2 (11-76 g/m2), respectively. Most of the nephrotoxicity persisted after cessation of IFO treatment. In conclusion, close monitoring of IFO nephrotoxicity should be started earlier in patients with high-dose cisplatin pretreatment. Tubular proteinuria, as indicated by beta2-microglobulinuria, was the most-sensitive marker for IFO nephrotoxicity. Long-term follow-up study for reversibility of IFO nephrotoxicity is in progress.

Adolescent↗

PubMed2001

TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis.

There is considerable evidence that osteoclasts are involved in the pathogenesis of focal bone erosion in rheumatoid arthritis. Tumor necrosis factor-related activation-induced cytokine, also known as receptor activator of nuclear factor-kappaB ligand (TRANCE/RANKL) is an essential factor for osteoclast differentiation. In addition to its role in osteoclast differentiation and activation, TRANCE/RANKL also functions to augment T-cell dendritic cell cooperative interactions. To further evaluate the role of osteoclasts in focal bone erosion in arthritis, we generated inflammatory arthritis in the TRANCE/RANKL knockout mouse using a serum transfer model that bypasses the requirement for T-cell activation. These animals exhibit an osteopetrotic phenotype characterized by the absence of osteoclasts. Inflammation, measured by clinical signs of arthritis and histopathological scoring, was comparable in wild-type and TRANCE/RANKL knockout mice. Microcomputed tomography and histopathological analysis demonstrated that the degree of bone erosion in TRANCE/RANKL knockout mice was dramatically reduced compared to that seen in control littermate mice. In contrast, cartilage erosion was present in both control littermate and TRANCE/RANKL knockout mice. These results confirm the central role of osteoclasts in the pathogenesis of bone erosion in arthritis and demonstrate distinct mechanisms of cartilage destruction and bone erosion in this animal model of arthritis.

Animals↗

PubMed2001

Poly(ethylene glycol)-poly(L-lactide) diblock copolymer prevents aggregation of poly(L-lactide) microspheres during ethylene oxide gas sterilization.

Sterilization procedure is one of the most important obstacles in the clinical applications of biodegradable microspheres. The microspheres prepared with poly(alpha-hydroxy acid) were severely aggregated during ethylene oxide (EO) gas sterilization, and could not be used in clinical applications. In this study, the effects of EO gas sterilization on the poly(L-lactide) (PLLA) microspheres were analyzed by nuclear magnetic resonance spectroscopy (1H-NMR), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), scanning electron microscope (SEM) and size fractionation. The aggregation between the microspheres might be stimulated by high mobility of amorphous regions of PLLA on the microsphere surfaces since both water vapor and gas mixture can reduce glass transition temperature (Tg) of PLLA below the sterilization temperature. During EO gas sterilization, there were no changes in the molecular structure and the molecular weight of PLLA in microspheres, but there were changes in the crystallinity of PLLA in microspheres. In this study, poly(L-lactide)-poly(ethylene glycol) diblock copolymers (PLE) were blended with PLLA homopolymers in various ratios to design the microsphere suitable for EO gas sterilization. Aggregation of PLLA microspheres was markedly prevented when more than 4wt% of PLE was blended in the microspheres. This inhibition effect on aggregation may be due to the increased initial crystallinity of the microspheres, which help to maintain the microsphere morphology during EO gas sterilization.

Calorimetry, Differential Scanning↗

PubMed2001

A simple and efficient in vitro method for metabolism studies of radiotracers.

In vitro metabolism of acetylcholinesterase inhibitors containing 3-[(18)F]fluoromethylbenzyl- ([(18)F]1) and 4-[(18)F]fluorobenzyl-piperidine moieties ([(18)F]2) was studied and compared with the in vivo metabolism. Defluorination of the [(18)F]1 mainly occurred to generate [(18)F]fluoride ion both in vitro and in vivo. In contrast, the [(18)F]2 was converted into an unknown polar metabolite in both metabolism methods and another metabolite, 4-[(18)F]fluorobenzoic acid in vitro. These results demonstrated that the in vitro method can be used to predict the in vivo metabolism of both radiotracers.

Animals↗

PubMed2001

Safety becomes danger: dilemmas of drug-use in public space.

This paper provides a socio-spatial analysis of injecting drug-use in public space. It focuses on one urban district in Melbourne, Australia, which has become strongly identified with heroin sale and use in public space. Selling activities are camouflaged within a diverse street life while injecting sites are dispersed through a broad diversity of laneways, car parks and toilets. These injecting zones occupy liminal places which slide between categories of private and public, and which mediate complex and paradoxical relations between safety and danger. Those who inject in public space are caught in a dilemma--needing both privacy and exposure in the event of an overdose, safety from police becomes danger from an overdose. This empirical work, based on interview and spatial analysis, is presented as a basis for theorizing the socio-spatial construction of heroin use and for assessing the prospects for safe injecting.

Drug Overdose↗

PubMed2001

Etiology and prevention of substance use among Asian American youth.

Among populations identified by the U.S. Bureau of the Census, it is anticipated that the Asian/Pacific Islander (API) population will experience the greatest change between 1990 and 2050 (U.S. Bureau of the Census. [1996, February]. Current population reports. Series P25-1130. Washington, DC: U.S. Government printing office). Limited studies focus on APIs as a racial group and still fewer disaggregate samples to specific ethnic Asian subgroupings. This paper begins with definitions of the API communities, then examines rates of adolescent drug use, risk and protective factors, and preventive intervention effectiveness focused on API communities. The limited epidemiological data suggest that in general, APIs are at a relatively lower risk for drug use than youth from most other ethnic groups. However, the available data also suggest that use may not be as low as generally assumed with rates for alcohol use, smoking, and some illicit drugs being equal to or exceeding those of African Americans and European Americans. Despite the paucity of available data on particular Asian subgroups, the available data demonstrate that there are differences among API subgroups, underscoring the importance of identifying Asian subgroups when studying substance use and when planning prevention and treatment. The limited data examining the etiology of drug use across API subgroups suggests that some of the risk and protective factors derived from majority based research may also be predictors for these populations. These data support the utility of examining the generalizability of existing tested prevention approaches among different API communities. Finally, further efforts should be made to encourage and support the evaluation of community-based programs that already target and deliver services to API youth.

Adolescent↗

PubMed2001

Recurrent focal segmental glomerulosclerosis following renal transplantation in Korean pediatric patients.

The recurrence of focal segmental glomerulosclerosis (FSGS) in transplants is a well-known problem in pediatric renal transplantation (Tx). Recently, the race of the recipient was recognized as a major variable associated with disease recurrence. In view of this finding, we report on our single-center experience of FSGS recurrence in Korean children, an ethnically homogeneous Far East Asian population. Clinical records and renal biopsy specimens, both native and graft, were reviewed for all pediatric renal Txs (recipient age < or = 18 yr) performed at Seoul National University Hospital from 1984 to 1999. Twenty-two children with primary FSGS received 22 allografts for renal replacement. The mean age of disease onset in these patients was 5.9 yr. The grafts were from 12 living-related, six living-unrelated, and four cadaveric donors, and all recipients were immunosuppressed with cyclosporin A (CsA)-based regimens. Post-transplant recurrence of FSGS was confirmed in nine patients (41%). Long-term graft survival in recurrent and non-recurrent groups was not significantly different. Risk factor analysis showed that patients with a disease duration shorter than 48 months (odds ratio 11.7, 95% CI 1.53-89.1) and a glomerulosclerosis percentage of < 55% by renal biopsy (odds ratio 16.0, 95% CI 1.45-176) were at greater risk of disease recurrence. These results suggest that Korean children are similar to non-African-American youngsters in the USA and Europe with respect to post-transplant recurrence of FSGS. The same may be true of other Far Eastern Asian children.

Asian People↗

PubMed2001

Inhibition effect of new farnesol derivatives on all-trans-retinoic acid metabolism.

All-trans-retinoic acid (atRA) is a promising anticancer and antiwrinkle drug. However, its clinical application is limited because it is rapidly metabolized by the induced cytochrome P450 (P450). In this study, farnesol derivatives are proposed as new inhibitors to prevent P450-mediated metabolism. The farnesol derivatives were suc-farnesol and mal-farnesol, which were synthesized by the chemical conjugation of farnesol with succinic anhydride and maleic anhydride, respectively. The inhibition effects of farnesol, farnesoic acid, and farnesol derivatives on the atRA metabolism were evaluated in microsome and in AMC-HN-6 cells. In the microsome experiment, suc-farnesol and mal-farnesol strongly inhibited atRA metabolism at 10(minus;4) mol/L concentration by as much as 61% and 77%, respectively. In the cell experiment, the inhibition effects of farnesol derivatives on the atRA metabolism showed similar tendency as the results in the microsome experiment, even if the effect was somewhat decreased. Effects of farnesoic acid and farnesol, however, were not significant. This research suggests that carboxylic end groups, such as atRA and hydrophobicity, might be important factors causing the higher inhibition effect, and that derivatization of farnesol can be 1 method to develop new inhibitors of atRA metabolism.

Antimetabolites↗

PubMed2001

Effects of the estrous cycle, pregnancy, and interferon tau on 2',5'-oligoadenylate synthetase expression in the ovine uterus.

The enzymes which comprise the 2',5'-oligoadenylate synthetase (OAS) family are interferon (IFN) stimulated genes which regulate ribonuclease L antiviral responses and may play additional roles in control of cellular growth and differentiation. This study characterized OAS expression in the endometrium of cyclic and pregnant ewes as well as determined effects of IFNtau and progesterone on OAS expression in cyclic or ovariectomized ewes and in endometrial epithelial and stromal cell lines. In cyclic ewes, low levels of OAS protein were detected in the endometrial stroma (S) and glandular epithelium (GE). In early pregnant ewes, OAS expression increased in the S and GE on Day 15. OAS expression in the lumenal epithelium (LE) was not detected in uteri from either cyclic or pregnant ewes. Intrauterine administration of IFNtau stimulated OAS expression in the S and GE, and this effect of IFNtau was dependent on progesterone. Ovine endometrial LE, GE, and S cell lines responded to IFNtau with induction of OAS proteins. In all three cell lines, the 40/46-kDa OAS forms were induced by IFNtau, whereas the 100-kDa OAS form appeared to be constitutively expressed and not affected by IFNtau. The 69/71-kDa OAS forms were induced by IFNtau in the S and GE cell lines, but not in the LE. Collectively, these results indicate that OAS expression in the endometrial S and GE of the early pregnant ovine uterus is directly regulated by IFNtau from conceptus and requires the presence of progesterone.

2',5'-Oligoadenylate Synthetase↗

PubMed2001

Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular epithelium of the ovine uterus.

Interferon tau (IFNtau) is the signal for maternal recognition of pregnancy in ruminants. The positive effects of IFNtau on IFN-stimulated gene (ISG) expression are mediated by ISG factor 3 (ISGF3), which is composed of signal transducer and activator of transcription (Stat) 1, Stat 2, and IFN regulatory factor-9 (IRF-9), and by gamma-activated factor (GAF), which is a Stat 1 homodimer. Induction of ISGs, such as ISG17 and 2',5'-oligoadenylate synthetase, by IFNtau during pregnancy is limited to the endometrial stroma (S) and glandular epithelium (GE) of the ovine uterus. The IRF-2, a potent transcriptional repressor of ISG expression, is expressed in the luminal epithelium (LE). This study determined effects of the estrous cycle, pregnancy, and IFNtau on expression of Stat 1, Stat 2, IRF-9, IRF-1, and IRF-2 genes in the ovine endometrium. In cyclic ewes, Stat 1, Stat 2, IRF-1, and IRF-9 mRNA and protein were detected at low levels in the S and GE. During pregnancy, expression of these genes increased only in the S and GE. Expression of IRF-2 was detected only in the LE and superficial GE (sGE) of both cyclic and pregnant ewes. In cyclic ewes, intrauterine administration of IFNtau stimulated Stat 1, Stat 2, IRF-9, and IRF-1 expression in the endometrium. Ovine IRF-2 repressed transcriptional activity driven by IFN-stimulated response elements that bind ISGF3, but not by gamma-activation sequences that bind GAF. These results suggest that IRF-2 in the LE and sGE restricts IFNtau induction of ISGs to the S and GE. In the S and GE, IFNtau hyperactivation of ISG expression likely involves formation and actions of the transcription factors ISGF3 and, perhaps, IRF-1.

Animals↗

PubMed2001

Image reconstruction using the wavelet transform for positron emission tomography.

We conducted positron emission tomography (PET) image reconstruction experiments using the wavelet transform. The Wavelet-Vaguelette decomposition was used as a framework from which expressions for the necessary wavelet coefficients might be derived, and then the wavelet shrinkage was applied to the wavelet coefficients for the reconstruction (WVS). The performances of WVS were evaluated and compared with those of the filtered back-projection (FBP) using software phantoms, physical phantoms, and human PET studies. The results demonstrated that WVS gave stable reconstruction over the range of shrinkage parameters and provided better noise and spatial resolution characteristics than FBP.

Algorithms↗

PubMed2001

TDAG51 is not essential for Fas/CD95 regulation and apoptosis in vivo.

Fas/CD95 is a key regulator of apoptotic signaling, which is crucial for the maintenance of homeostasis in peripheral lymphoid organs. TDAG51 has been shown to play critical roles in the up-regulation of Fas gene expression and T-cell apoptosis in vitro. In order to identify the role of TDAG51 in vivo, we generated TDAG51-deficient (TDAG51-/-) mice. Northern blotting revealed no expression of TDAG51 in TDAG51-/- mice, indicating that the TDAG51 gene was successfully targeted. TDAG51-/- mice were healthy and showed no gross developmental abnormalities. While Fas-deficient mice display marked lymphadenopathy, splenomegaly, and lymphocytosis, TDAG51-/- mice had no apparent defects in secondary lymphoid organs. Although TDAG51 is required for up-regulation of Fas expression in T-cell hybridomas, TDAG51-/- mice expressed normal levels of Fas and had normal T-cell apoptosis. Therefore, we conclude that TDAG51 is not essential for Fas up-regulation and T-cell apoptosis in vivo. There are several known homologs of TDAG51, and these homologs may substitute for TDAG51 in TDAG51-/- mice.

Animals↗

PubMed2001

Effects of ethylene oxide gas sterilization on physical properties of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) microspheres.

The aggregation of poly(alpha-hydroxy acid) microspheres during ethylene oxide (EO) gas sterilization makes it difficult for the microspheres to be used in clinical applications. In this study, six kinds of PLLA-PEG-PLLA triblock copolymers (TriPLE) were synthesized with various composition ratios of PEG/PLLA in the range of 0.012 to 0.103. TriPLE microspheres were prepared by the oil-in-water emulsion method. TriPLE microspheres were characterized by using 1H-NMR, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). After sterilization by EO gas at 55 degrees C, the microspheres were analyzed by scanning electron microscope (SEM), laser diffractometry, standard sieves, X-ray diffraction (XRD), GPC, and DSC. When the composition ratio of PEG/PLLA was above 0.02, the initial crystallinity of TriPLE in microspheres was as high as 50%, and the microspheres were suitable to be sterilized by EO gas. On the other hand, TriPLE microspheres, which had composition ratios of PEG/PLLA below 0.02, had low initial crystallinities of about 30%, and aggregated during EO gas sterilization. For these microspheres, crystallinity increased up to 50% during the sterilization, whereas other TriPLE microspheres did not show any changes in crystallinity. Therefore, the aggregation of TriPLE microspheres during EO gas sterilization was markedly reduced as the initial crystallinity of TriPLE in the microspheres was increased.

Calorimetry, Differential Scanning↗

PubMed2001

Cloning of the ovine estrogen receptor-alpha promoter and functional regulation by ovine interferon-tau.

Interferon-tau (IFNtau), the ruminant pregnancy recognition signal, inhibits transcription of the estrogen receptor alpha (ERalpha) gene in the endometrial lumenal epithelium of the sheep uterus, thereby abrogating production of luteolytic PGF(2alpha) pulses. The effects of IFNtau are mediated in part by IFN-stimulated response elements (ISREs) and IFN regulatory factor elements (IRFEs). The promoter/enhancer region of the ovine ERalpha gene was cloned, sequenced, and predicted to contain four IRFEs and one ISRE. Electrophoretic mobility shift assays indicated that the -2110 IRFE bound only IRF-1, whereas the -1877 IRFE and the -1284 ISRE were functional in binding IRF-1 and IRF-2. IFNtau inhibited transcriptional activity of the 2.7-kb ovine ERalpha promoter in transfection assays using ovine lumenal epithelium cells. Analyses of sequential 5'-deletion mutants of the ovine ERalpha promoter indicated that the effects of IFNtau may be mediated by IRFEs as well as other elements. Overexpression of ovine IRF-2, but not IRF-1, inhibited transcriptional activity of several regions of the ovine ERalpha promoter containing an IRFE or an ISRE as well as some, but not all, regions lacking these elements.

Animals↗