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Biomedical subjects

J S Choi

Publications and source records attributed to J S Choi.

At least 37 records · Page 2Linked to original sources

Expression of osteopontin mRNA in developing rat brainstem and cerebellum.

This study was undertaken to investigate the developmental expression of osteopontin (OPN) in the rat brainstem and cerebellum by Northern blotting and in situ hybridization. The expression of OPN was noted in the mesencephalic Vth nucleus initially at embryonic day 16 (E16). At E20, the labeling extended into other brainstem nuclei including the cochlear, vestibular, facial motor, and hypoglossal nuclei. During the first week of postnatal life, the OPN signal in the brainstem increased markedly, and by P14, OPN expression was found in functionally diverse areas including motor-related areas, sensory relay nuclei, and the reticular formation. The adult labeling pattern was established in central neurons at this time. These results corresponded well with those from Northern blot analysis. On the basis of morphological and distribution criteria, the OPN signal in several nuclei appeared to be contained exclusively within neuronal soma. OPN expression in neurons occurred during the period of neuronal differentiation and increased with maturation. Our results therefore suggest that OPN contributes to developmental processes, including the differentiation and maturation of specific neuronal populations, in the rat brain.

Animals↗

Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1.

The effects of fluoxetine and its major metabolite, norfluoxetine, were studied using the patch-clamp technique on the cloned neuronal rat K(+) channel Kv3.1, expressed in Chinese hamster ovary cells. In whole-cell recordings, fluoxetine and norfluoxetine inhibited Kv3.1 currents in a reversible concentration-dependent manner, with an IC(50) value and a Hill coefficient of 13.11+/-0.91 microM and 1.33+/-0.08 for fluoxetine and 0.80+/-0.06 microM and 1.65+/-0.08 for norfluoxetine at +40 mV, respectively. In inside-out patches, norfluoxetine applied to the cytoplasmic surface inhibited Kv3.1 with an IC(50) value of 0.19+/-0.01 microM. The inhibition of Kv3.1 currents by both drugs was characterized by an acceleration in the apparent rate of current decay, without modification of the activation time course and with relatively fewer effects on peak amplitude. The degree of inhibition of Kv3.1 by norfluoxetine was voltage-dependent. The inhibition increased steeply between 0 and +30 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +30 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.31+/-0.05. The association (k(+1)) and dissociation (k(-1)) rate constants for norfluoxetine-induced inhibition of Kv3.1 were 21.70+/-3.39 microM(-1) s(-1) and 14.68+/-3.94 s(-1), respectively. The theoretical K(D) value derived by k(-1)/k(+1) yielded 0.68 microM. Norfluoxetine did not affect the ion selectivity of Kv3.1. The reversal potential under control conditions was about -85 mV and was not affected by norfluoxetine. Norfluoxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of norfluoxetine, were superimposed. The voltage dependence of steady-state inactivation was not changed by the drug. Norfluoxetine produced use-dependent inhibition of Kv3.1 at a frequency of 1 Hz and slowed the recovery from inactivation. It is concluded that at clinically relevant concentrations, both fluoxetine and its major metabolite norfluoxetine inhibit Kv3.1, and that norfluoxetine directly inhibits Kv3.1 as an open channel blocker.

Algorithms↗

A new cyclic phenyllactamide from Salvia miltiorrhiza.

From the rhizome of Salvia miltiorrhiza, a new cyclic phenyllactamide was isolated and characterized as 2,10,11-trihydroxy-8-methoxy-1,6,7,8-tetrahydro-2H-benzo[e]azecine-3,5-dione (1) from spectroscopic evidence. The new compound was found to be a scavenger of 1,1-diphenyl-2-picrylhydrazyl radical.

Acetamides↗

Peroxynitrite scavenging and cytoprotective activity of 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether from the marine alga Symphyocladia latiuscula.

Peroxynitrite (ONOO(-)), formed from the reaction of superoxide (O(2)*(-)) and nitric oxide (*NO), is a cytotoxic species that can oxidize several cellular components such as proteins, lipids, and DNA. It has been implicated in diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, and atherosclerosis. Due to the lack of endogenous enzymes responsible for ONOO(-) inactivation, developing a specific ONOO(-) scavenger is of considerable importance. The aim of this study was to evaluate the ability of marine natural products to scavenge ONOO(-) and to protect cells against ONOO(-). Methanolic extracts of 17 marine alga were tested for their ONOO(-) scavenging activity. Among them, Symphyocladia latiuscula showed the potent scavenging activity. CH(2)CH(2) fraction was partitioned with CH(2)CH(2) following n-hexanal extraction from the methanol extract of S. latiuscula. It was highly effective for ONOO(-) scavenging activity. Further analysis of the active fractionated extract identified 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB) as a potent ONOO(-) scavenger. The data demonstrated that TDB led to decreased ONOO(-)-mediated nitration of tyrosine through electron donation. TDB showed significant inhibition on nitration of bovine serum albumin and low-density lipoprotein by ONOO(-) in a dose-dependent manner. It also provided cytoprotection from cell damage induced by ONOO(-). TDB can be developed as an effective peroxynitrite scavenger for the prevention of the involved diseases.

Animals↗

Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status.

p21Waf1 (p21), p27Kip1 (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, studies on these cell cycle regulators in ductal carcinoma in situ (DCIS) have been extremely limited. Therefore, we studied the immunohistochemical expression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared the findings with the clinicopathologic parameters (age, tumor size, gross type, histologic type, histologic grade, necrosis and mitotic index), p53 and estrogen receptor (ER) status. A significant correlation was found between positive p21 immunoreactivity (67.3% of the cases) and well-differentiated histologic grade, non-comedo type, ER-positive and p53-negative (p53-) status. DCIS with p21+/p53- is likely to be the non-comedo type. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) correlated with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cyclin D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.

Adult↗

New galactolipids from the marine bacillariophycean microalga Nitzschia sp.

Two new galactopyranosyldiacylglycerols have been isolated from the marine bacillariophycean microalga Nitzschia sp. and their structures were determined as (2S)-3-O-beta-D-galactopyranosyl-1,2-di-O-(9Z-hexadecenoyl)glycerol (1) and (2S)-3-O-beta-D-galactopyranosyl-1-O-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-O-(9Z-hexadecenoyl)glycerol (2) by physicochemical evidence.

Chromatography, High Pressure Liquid↗

Expression of vascular endothelial growth factor and inducible nitric oxide synthase in pterygia.

PURPOSE: To evaluate the expression of vascular endothelial growth factor (VEGF) in pterygium and investigate the interrelationships between VEGF and nitric oxide (NO) in the development of pterygia. METHODS: Specimens of normal conjunctiva acquired incidentally to conjunctival transplantation during pterygium and strabismus surgery and the excised pterygium were used in this study. Cryopreserved tissue specimens consisting of normal conjunctiva and pterygium were used to study the expression of VEGF and inducible NO synthetase (iNOS), using immunohistochemistry. For confirmation of NOS activity, reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was done. Enzyme-linked immunosorbent assay (ELISA) for detection and quantification of VEGF was performed. RESULTS: Expression of VEGF and iNOS was strongly revealed mainly in the epithelium of the head portions of pterygial specimens, although not in the epithelium of conjunctival ones. Pterygial epithelium was stained with NADPH diaphorase, confirming NOS activity. ELISA showed a greater amount of VEGF in pterygium (11.7 +/- 2.1 pg/mg) compared with normal conjunctiva (4 +/- 0.47 pg/mg) ( p < 0.05). CONCLUSION: These data are the first to demonstrate that VEGF and NO may play an important role in the development of pterygium and to identify VEGF and NO in the epithelium of pterygium. We hypothesize that environmental stress, such as ultraviolet irradiation and local inflammation stimulate the elaboration of NO and VEGF, resulting in the conjunctival fibrovascular ingrowth characteristic of pterygium.

Adult↗

Outcome and management of patients with large rectoanal intussusception.

OBJECTIVES: Rectoanal intussusception is the funnel-shaped infolding of the rectum, which occurs during evacuation. The aims of this study were to evaluate the risk of full thickness rectal prolapse during follow-up of patients with large rectoanal intussusception, and whether therapy improved functional outcome. METHODS: Between September 1988 and July 1997, patients diagnosed with a large rectoanal intussusception by cinedefecography (intussusception > or = 10 mm, extending into the anal canal) were retrospectively evaluated. Patients with full thickness rectal prolapse on physical examination or cinedefecography were excluded, as were patients with colonic inertia or a history of surgery for rectal prolapse. The patients were divided into three groups according to the treatment received: group I, conservative dietary therapy; group II, biofeedback; and group III, surgery. Outcomes were obtained by postal questionnaires or telephone interviews. Parameters included age, gender, past medical and surgical history, change of bowel habits, fecal incontinence score, and development of full thickness rectal prolapse. RESULTS: Of the 63 patients, 18 were excluded (seven patients had confirmed full thickness rectal prolapse, four had previous surgery for rectal prolapse, three had colonic inertia, and four died). Follow-up data were obtained in 36 (80%) of the remaining 45 patients. The mean follow-up of this group was 45 months (range, 12-118 months). There were 34 women and two men, with a mean age of 72.4 yr (range, 37-91 yr). The mean size of the intussusception was 2.2 cm (range, 1.0-5.0 cm). The patients were classified as follows: group I, 13 patients (36.1%); group II, 13 patients (36.1%); and group III, 10 patients (27.8%). Subjectively, symptoms improved in five (38.5%), four (30.8%), and six (60.0%) patients in the three groups (p > 0.05). Among the patients with constipation, the decrease in numbers of assisted bowel movements per week (time of diagnosis to present) was significantly greater in group II compared to group 1 (8.1+/-2.8 vs 0.8+/-0.5, respectively, p = 0.004). Among the patients with incontinence, incontinence scores improved more in group II as compared to either group I or group III (time of diagnosis to present, 3.7+/-4.2 to 1.1+/-5.4 vs 1.4+/-2.2, respectively, p > 0.05). Six patients (two in group I, three in group II, and one in group III) had the sensation of rectal prolapse on evacuation; however, only one patient in group I developed full thickness rectal prolapse. CONCLUSIONS: This study demonstrated that the risk of full thickness rectal prolapse developing in patients medically treated for large intussusception is very small (1/26, 3.8%). Moreover, biofeedback is beneficial to improve the symptoms of both constipation and incontinence in these patients. Therefore, biofeedback should be considered as the initial therapy of choice for large rectoanal intussusception.

Adult↗

Epidemiologic and clinical survey of Behcet's disease in Korea: the first multicenter study.

The prevalence of Behcet's disease is the highest in the East Asian and the Mediterranean countries. Behcet's disease is also distributed in the Asian countries, but the nationwide survey has not been performed in Korea yet. The Korean Study Group for Behcet's Disease, founded in 1999, conducted a multicenter, retrospective survey on epidemiologic and clinical features of the patients with Behcet's disease from 20 hospitals around the nation from 1997 to 1999. Of 3,497 patients, 1,527 were classified into complete or incomplete type of Behcet's disease according to the revised Shimizu's classification. The sex ratio was 1:1.75 with the female predominance. Geographical distribution showed the highest frequency in Seoul (38.5%). Clinically, 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions and 50.9% had ocular lesions. As for the minor clinical manifestations, articular symptoms were the most frequent. The pathergy test showed positive in 15.4% of patients and revealed a higher positive rate in males (20.2%) than in females (12.7%). In conclusion, we performed the first multicenter study on Behcet's disease in Korea and revealed the female predominance, higher frequency of ocular lesions, and lower positivity of pathergy test in the patients.

Adolescent↗

Amygdala lesions block conditioned enhancement of the early component of the rat eyeblink reflex.

A tone conditioned stimulus (CS) previously paired with a grid shock unconditioned stimulus (US) can greatly enhance the early electromyographic (EMG) component (R1) of the rat eyeblink reflex. The hypothesis that the central nucleus of the amygdala (ACe) is an essential part of the circuitry mediating conditioned R1 enhancement was tested. After bilateral ACe lesions (L) or a sham operation (S), rats received paired presentations of the CS and US (P) or explicitly unpaired CS and US presentations (U), resulting in 4 groups: P/S, P/L, U/S, and U/L. ACe lesions completely prevented conditioned R1 enhancement, which was only exhibited in Group P/S. In the latter group, the "preextinction" conditioned enhancement effect was roughly a 2-fold increase in the R1 magnitude. Circuit-level mechanisms are discussed, and some advantages of the eyeblink EMG response in this general conditioning paradigm are considered.

Acoustic Stimulation↗

Complestatin is a noncompetitive peptide antagonist of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors: secure blockade of ischemic neuronal death.

Complestatin, a peptide derived from Streptomyces, was found to protect cultured cortical neurons from excitotoxicity induced by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate. This neuroprotective behavior of complestatin was attributed to a blockade of Ca2+ ion entry and accumulation, after the activation of NMDA and AMPA/kainate receptors. Complestatin reversibly interfered with NMDA- and AMPA-mediated excitatory synaptic transmission. Complestatin also protected cortical neurons from prolonged deprivation of oxygen and glucose, more effectively than combined antagonists of NMDA and AMPA/kainate receptors. Neurotoxicity, evolving within 1 to 2 days after continuous exposure to combined NMDA and AMPA/kainate antagonists, was not observed in cortical cell cultures that were exposed to complestatin. Finally, complestatin dose dependently prevented neuronal death evolving within the inner nuclear and ganglion cell layers, after transient retinal ischemia. We conclude that complestatin possesses novel pharmacological properties that effectively prevent excitotoxicity under certain pathological conditions.

Animals↗

Proteome analysis of light-induced proteins in Synechocystis sp. PCC 6803: identification of proteins separated by 2D-PAGE using N-terminal sequencing and MALDI-TOF MS.

The cyanobacterium Synechocystis sp. PCC 6803 is an ideal model organism for the proteome study of light-induced gene expression because the whole genomic sequence has been determined. The soluble proteins extracted from light- and dark-cultured cells were separated by two-dimensional polyacrylamide gel electrophoresis. Light-induced protein spots electroblotted on a polyvinyldiene difluoride membrane were analyzed by N-terminal Edman sequence determination and followed by CyanoBase. The tryptic digests of some proteins were also confirmed by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) and MS-Fit search. Interestingly, eight proteins were related to photosynthesis and respiration (RbcS/L, CbbA, Gap2, AtpB, CpcB, PsbO, and PsbU). Four proteins (SodB, DnaK, GroEL2, and Tig) were involved in cellular processes and the functions of another two proteins (rehydrin and membrane protein) were unknown. The proteome analysis by N-terminal Edman sequencing and MALDI-TOF enabled us to characterize one-shot protein profiles expressed under different physiological conditions.

Amino Acid Sequence↗

Enhanced bioavailability by buccal administration of triamcinolone acetonide from the bioadhesive gels in rabbits.

The pharmacokinetics and bioavailability of triamcinolone acetonide were determined to investigate buccal absorption from the mucoadhesive gels in rabbits. The enhancing effect of sodium deoxycholate as an enhancer on the buccal absorption of triamcinolone acetonide from the mucoadhesive gels was evaluated in rabbits. Thus, 2 mg/kg of triamcinolone acetonide was administered from the mucoadhesive gels containing an enhancer (enhancer group) or not (control group) via the buccal routes and compared with intravenous routes (1 mg/kg, i.v. group). AUC of the control, enhancer and i.v group were 2374+/-915, 3778+/-1721 and 3945+/-2085 h ng/ml, respectively, and the absolutive bioavailability of enhancer or i.v to control group were 159.14 or 332.35%, respectively. The average C(max) of control and enhancer group were 263+/-159 and 362+/-201 ng/ml, and the mean T(max) of the control group and enhancer group were 5.00+/-1.67 and 4.33+/-0.82 h, respectively, but there was no significant difference. As the triamcinolone acetonide gels containing sodium deoxycholate as an enhancer was administered to rabbits via the buccal routes, the relative bioavailability showed about 1.59-fold compared with the control group. Buccal administration of triamcinolone acetonide gels containing sodium deoxycholate as an enhancer to rabbits showed a relatively constant, sustained blood concentration with minimal fluctuation.

Adhesives↗

Failure to activate NF-kappaB promotes apoptosis of retinal ganglion cells following optic nerve transection.

NF-kappaB is a transcription factor, which is activated by various stimuli. One of the well-known activators of NF-kappaB is oxidative stress, which is a cause of cell death in some tissue, or cell types. Optic nerve transection, axotomy, results in retinal cell death, because of oxidative stress, deprivation of neurotrophic factors, etc. Since it has been hypothesized that the retinal ganglion cell death after axotomy is due to the generation of reactive oxygen species, we investigated whether NF-kappaB is involved in the retinal cell death after axotomy. This study was performed to investigate the role of NF-kappaB in retinal ganglion cell death after optic nerve transection. We used double staining experiment by using anti-NF-kappaB antibody and ethidium bromide to observe the correlation of NF-kappaB activation and the cell death. NF-kappaB was observed only in the surviving cells. NF-kappaB translocation was observed 3 days after the optic nerve transection. The NF-kappaB inhibitor, sulfasalazine, was used to block the activation of NF-kappaB in the axotomized retina, and the number of ganglion cells was quantified using retrograde in the presence or absence of sulfasalazine after axotomy. Inhibition of NF-kappaB by sulfasalazine accelerated the degeneration of ganglion cells in the retina. The results suggest that the activated NF-kappaB plays a protective role from the cell death in the injured ganglion cells.

Animals↗

Inhibition of NFkappaB by methyl chlorogenate from Eriobotrya japonica.

Methylchlorogenic acid (MC) is one of the main components in the leaves of Eriobotrya japonica. We previously reported that MC is the most potent antioxidant among several components of Eriobotrya japonica, and its antioxidant activity is stronger than that of chlorogenic acid. Antioxidants are expected to inhibit redox-sensitive NFkappaB activation since NFkappaB is readily influenced by cellular oxidative state. Based on these findings, in vivo experiments with MC were conducted to determine its ability to downregulate the NFkappaB activation in mouse liver. Results clearly showed that MC is a potent suppressor of BHP-induced NFkappaB activation. We observed a significant reduction by MC on BHP-induced translocation of p65 subunit of NFkappaB. This may be due to formation of p50/p65 heterodimer, which is mainly inducible NFkappaB. MC slightly blocked the BHP-induced IkappaB alpha degradation. There is a possibility of IkappaB alpha resynthesis via activated NFkappaB during a 5 h waiting period following BHP injection. The present results suggest that MC may inhibit NFkappaB activation, exhibiting its ability to downregulate the NFkappaB-dependent gene expression. Thus, it can be expected that MC may have potential for therapeutic intervention on various NFkappaB-dependent pathological conditions such as inflammatory or possibly mutagenic processes.

Active Transport, Cell Nucleus↗