Biomedical subjects

S Y Jeong

Publications and source records attributed to S Y Jeong.

At least 19 recordsLinked to original sources

PubMed2004

Use of polyurethane with sustained release dexamethasone in delayed adjustable strabismus surgery.

AIM: To determine the effect of polyurethane film with sustained release dexamethasone (SRD) in delayed adjustable strabismus surgery. METHODS: A prospective, masked observer, controlled study was performed in rabbits. Thirty four rabbit eyes were divided into three groups. After recession of the superior rectus muscle (SRM), polyurethane film with or without SRD, or balanced salt solution was applied beneath and over SRM in the polyurethane-dexamethasone group (group P-D), polyurethane group (group P), and the control group (group C), respectively. Delayed adjustment was performed once on each SRM at 4 and 6 weeks postoperatively by a masked observer. The possible length to adjust and the necessary force required for the adjustment, as well as the degree of any adhesions, were also evaluated. RESULTS: In the control group, adjustment was impossible in all of the eyes at 4 and 6 weeks postoperatively. In group P-D, adjustment was possible in 11 out of 11 eyes (11/11) 4 weeks postoperatively and in 10/11 eyes 6 weeks postoperatively. In group P, adjustment was possible in 9/11 eyes 4 weeks postoperatively and in 10/12 eyes 6 weeks postoperatively. CONCLUSIONS: Use of polyurethane film with and without SRD could delay adjustment in most eyes for up to 6 weeks postoperatively. Polyurethane is helpful for delaying adjustment in rabbit eyes until 6 weeks postoperatively without the need for frequent topical instillation of steroids.

Animals↗

PubMed2002

Self-assembled "nanocubicle" as a carrier for peroral insulin delivery.

AIMS/HYPOTHESIS: A patient with (insulin-dependent) diabetes mellitus receives at least one subcutaneous insulin injection a day to maintain low serum glucose concentrations. Since patients' compliance with such dosage regimens is too low, the development of an oral formula is clearly attractive. We present the development of a liquid formula that can be easily dispersed in water to produce particles named "nanocubicles" which efficiently encapsulate insulin. METHODS: Fasted streptozotocin-induced diabetic rats were administered orally with particles encapsulating insulin, and particles without insulin or soluble insulin in water. Groups of rats were also injected soluble insulin in PBS for control. Blood glucose concentration and insulin concentration were measured 1, 2, 3, 4 and 6 h after the administration of the insulin formulas. RESULTS: In vitro experiments show that the particles can be taken up by the Caco-2 cells at a high ratio. The serum glucose concentration was controlled for more than 6 h after oral insulin administration but returned to the basal concentration in 3 h when 1 IU/kg of insulin was injected intravenously. CONCLUSION/INTERPRETATION: Our biocompatible and stable oral insulin formulation is easy to prepare and produces reproducible hypoglycaemic effects, therefore we anticipate clinical acceptance and utilization of this form of insulin therapy.

Administration, Oral↗

PubMed2001

Nitric oxide directly activates large conductance Ca2+-activated K+ channels (rSlo).

We investigated whether nitric oxide (NO) directly activates the cloned alpha-subunit of large conductance Ca2+-activated K+ (Maxi-K) channels from rat brain (rSlo), expressed either in HEK293 cells or Xenopus oocytes. In inside-out patches, the application of S-nitroso-N-acetylpenicillamine (SNAP), a NO-releasing compound, reversibly activated the channel shifting the voltage dependent activation curve of the macroscopic Maxi-K current to the left by about 15 mV. Pretreatment of the patches with N-ethylmaleimide to alkylate free sulfhydryl groups did not prevent the effect of SNAP, suggesting that NO may directly interact with the channels. These results suggest that Maxi-K channels might be one of the physiological targets of NO in the brain.

Animals↗

PubMed2001

Induction of angiogenesis by expression of soluble type II transforming growth factor-beta receptor in mouse hepatoma.

The biological effect of transforming growth factor-beta (TGF-beta) is cell type-specific and complex. The precise role of TGF-beta is not clear in vivo. To elucidate the regulation mechanism of endogenous TGF-beta on hepatoma progression, we modified the MH129F mouse hepatoma cell with a retroviral vector encoding the extracellular region of type II TGF-beta receptor (TRII). Soluble TRII (TRIIs) blocked TGF-beta binding to TRII on the membrane of hepatoma cells. Growth of MH129F cells was inhibited by TGF-beta1 treatment; however, soluble TRII-overexpressing cells (MH129F/TRIIs) did not show any change in proliferation after TGF-beta1 treatment. MH129F/TRIIs cells also increased vascular endothelial growth factor (VEGF) expression, endothelial cell migration, and tube formation. Implantation of MH129F/TRIIs cells into C3H/He mice showed the significantly enhanced tumor formation. According to Western blot and protein kinase C assay, the expression of VEGF, KDR/flk-1 receptor, and endothelial nitric-oxide synthase was enhanced, and the phosphorylation activity of protein kinase C was increased up to 3.7-fold in MH129F/TRIIs tumors. Finally, a PECAM-1-stained intratumoral vessel was shown to be 4.2-fold higher in the MH129F/TRIIs tumor. These results indicate that VEGF expression is up-regulated by a blockade of endogenous TGF-beta signaling in TGF-beta-sensitive hepatoma cells and then stimulates angiogenesis and tumorigenicity. Therefore, we suggest that endogenous TGF-beta is a major regulator of the VEGF/flk-1-mediated angiogenesis pathway in hepatoma progression.

Animals↗

PubMed2001

SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein.

Genetic etiologies of at least 20% of autosomal dominant cerebellar ataxias (ADCAs) have yet to be clarified. We identified a novel spinocerebellar ataxia (SCA) form in four Japanese pedigrees which is caused by an abnormal CAG expansion in the TATA-binding protein (TBP) gene, a general transcription initiation factor. Consequently, it has been added to the group of polyglutamine diseases. This abnormal expansion of glutamine tracts in TBP bears 47--55 repeats, whereas the normal repeat number ranges from 29 to 42. Immunocytochemical examination of a postmortem brain which carried 48 CAG repeats detected neuronal intranuclear inclusion bodies that stained with anti-ubiquitin antibody, anti-TBP antibody and with the 1C2 antibody that recognizes specifically expanded pathological polyglutamine tracts. We therefore propose that this new disease be called SCA17 (TBP disease).

Adult↗

PubMed2001

Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.

Oil-in-water (o/w) type lipid emulsions were formulated by using 18 different natural oils and egg phosphatidylcholine (egg PC) to investigate how emulsion particle size and stability change with different oils. Cottonseed, linseed and evening primrose oils formed emulsions with very large and unstable particles. Squalene, light mineral oil and jojoba bean oil formed stable emulsions with small particles. The remaining natural oils formed moderately stable emulsions. Emulsions with smaller initial particle size were more stable than those with larger particles. The correlation between emulsion size made with different oils and two physical properties of the oils was also investigated. The o/w interfacial tension and particle size of the emulsion were inversely proportional. The effect of viscosity was less pronounced. To study how the oil component in the emulsion modulates the in vitro release characteristics of lipophilic drugs, three different emulsions loaded with two different drugs were prepared. Squalene, soybean oil and linseed oil emulsions represented the most, medium and the least stable systems, respectively. For the lipophilic drugs, release was the slowest from the most stable squalene emulsion, followed by soybean oil and then by linseed oil emulsions. Cationic emulsions were also prepared with the above three different oils as gene carriers. In vitro transfection activity was the highest for the most stable squalene emulsion followed by soybean oil and then by linseed oil emulsions. Even though the in vitro transfection activity of emulsions were lower than the liposome in the absence of serum, the activity of squalene emulsion, for instance, was ca. 30 times higher than that of liposome in the presence of 80% (v/v) serum. In conclusion, the choice of oil component in o/w emulsion is important in formulating emulsion-based drug or gene delivery systems.

Animals↗

PubMed2001

The genomic structure and expression of MJD, the Machado-Joseph disease gene.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder that is clinically characterized by cerebellar ataxia and various associated symptoms. The disease is caused by an unstable expansion of the CAG repeat in the MJD gene. This gene is mapped to chromosome 14q32.1. To determine its genomic structure, we constructed a contig composed of six cosmid clones and eight bacterial artificial chromosome (BAC) clones. It spans approximately 300kb and includes MJD. We also determined the complete sequence (175,330bp) of B445M7, a human BAC clone that contains MJD. The MJD gene was found to span 48,240bp and to contain 11 exons. Northern blot analysis showed that MJD mRNA is ubiquitously expressed in human tissues, and in at least four different sizes; namely, 1.4, 1.8, 4.5, and 7.5kb. These different mRNA species probably result from differential splicing and polyadenylation, as shown by sequences of the 21 independent cDNA clones isolated after the screening of four human cDNA libraries prepared from whole brain, caudate, retina, and testis. The sequences of these latter clones relative to the MJD gene in B445M7 indicate that there are three alternative splicing sites and eight polyadenylation signals in MJD that are used to generate the differently sized transcripts.

Alternative Splicing↗

PubMed2001

Optimization of lipid composition in cationic emulsion as in vitro and in vivo transfection agents.

PURPOSE: To enhance in vitro and in vivo transfection activity by optimizing lipid composition of cationic lipid emulsions. METHODS: Various emulsion formulations having different cationic lipids as emulsifiers, and additional helper lipids as co-emulsifiers, were prepared. The stability of the emulsion and its complex with DNA was investigated by measuring the particle size change in phosphate buffer saline (PBS) over a period of 20 days. The activity of the emulsions in transfecting pCMV-beta into COS-1 cells in the presence or absence of 80% serum was evaluated. We also evaluated in vivo transfection activity using intravenously administered pCMV-Luc+ as a reporter gene. RESULTS: Among the cationic emulsifiers, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) formed the most stable and efficient emulsion gene carrier. Addition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) increased in vitro transfection activity, but slightly compromised the stability of the emulsion. The loss was compensated for by including small amounts of Tween 80 in the emulsion. The in vitro and in vivo transfection activities were also increased by adding Tween 80. Even though in vitro transfection activity of liposomes was high in the absence of serum, the transfection activity of emulsions was far greater than that of liposomes in the presence of serum and for in vivo applications. CONCLUSIONS: By including DOPE as an endosomolytic agent and Tween 80 as a stabilization agent, the cationic emulsion becomes a more potent gene carrier for in vitro and in vivo applications, especially in the presence of serum.

3T3 Cells↗

PubMed2001

NC-1500 prevents concanavalin A-induced mice hepatitis without affecting cytokine gene expression.

NC-1500 is a dihydropyridine type calcium channel blocker. The effect of NC-1500 on mice concanavalin A-induced hepatitis was examined. Treatment of mice with concanavalin A (Con A) caused elevation of plasma transaminase. Pretreatment of mice with NC-1500 (3, 10 and 30 mg/kg, p.o.) prevented this Con A-induced elevation of plasma transaminase. Treatment of mice with Con A induced tumor necrosis factor-alpha (TNF-alpha) mRNA expression in the liver. However, NC-1500 (30 mg/kg, p.o.) did not affect this Con A-induced TNF-alpha mRNA expression in the liver. The present results showed that NC-1500 inhibited Con A-induced hepatitis without affecting TNF-alpha mRNA expression in the liver.

Alanine Transaminase↗

PubMed2001

Expression of the alpha1D subunit of the L-type voltage gated calcium channel in human liver.

Calcium channel blocker is useful for a variety of purposes and is effective for preventing hepatitis elicited by different inducers, suggesting its possible clinical application for treating hepatitis. The alpha1-subunit of the dihydropyridine-sensitive L-type calcium channel is a target of calcium channel blocker. For clinical application of calcium channel blocker, it is important to analyze the expression of the L-type calcium channel in the liver. However, the subtype of the L-type calcium channel alpha1-subunit expressed in the liver was not known. In the present study, the alpha1-subunit of the calcium channel expressed in human liver was systematically analyzed. The alpha1D subunit of the dihydropyridine-sensitive L-type voltage gated calcium channel is expressed relatively strongly in the liver and may play an important role in the liver.

Calcium Channels, L-Type↗

PubMed2000

Induction of apoptosis in human leukemia cells by 3-deazaadenosine is mediated by caspase-3-like activity.

3-Deazaadenosine (DZA), one of the potent inhibitors of S-adenosylhomocysteine hydrolase, is known to possess several biological properties including an induction of apoptosis. To evaluate a possibility that DZA may be utilized for the treatment of human leukemia, we studied molecular events of cell death induced by DZA in human leukemia HL-60 and U-937 cells. DZA induced a specific cleavage of poly ADP-ribose polymerase (PARP) and an activation of the cysteine protease caspase-3/CPP32 which is known to cleave PARP. DZA-mediated nuclear DNA-fragmentation was completely blocked in the presence of a universal inhibitor of caspases (z-VAD-fmk) or the specific inhibitor of caspase-3 (z-DEVD-fmk) unlike of cycloheximide (CHX). DNA fragmentation was preceded by the lowering of c-myc mRNA in the DZA treated cells. In addition, DZA-induced apoptosis was blocked by pretreatment with adenosine transporter inhibitors such as nitrobenzylthioinosine (NBTI) and dipyridamole (DPD). Taken together, these results demonstrate that DZA-induced apoptosis initiated through an active transport of DZA into human leukemia cells, is dependent on the caspase-3-like activity without de novo synthesis of proteins and possibly involves c-myc down-regulation.

Adenosine↗

PubMed2000

Germline mutations of the dpc4 gene in Korean juvenile polyposis patients.

Juvenile polyposis is an uncommon condition characterized by the development of multiple (usually more than 5) juvenile polyps in the gastrointestinal tract, especially in the colon. This disease usually occurs during childhood, and is inherited in an autosomal dominant fashion. It has been suggested that the dpc4 (deleted in pancreatic carcinoma, locus 4) gene, which is located on chromosome 18q21.1, might cause juvenile polyposis. The dpc4 (smad4) gene is a candidate tumor-suppressor gene and may play a role in the TGF-beta-signaling pathway. To confirm the idea that alterations of the dpc4 gene may result in juvenile polyposis, we screened 5 Korean juvenile-polyposis patients by PCR-SSCP (single-strand conformation polymorphism) analysis and bi-directional sequencing. There were germline mutations of the dpc4 gene in 3 out of the 5 patients: 2 had a genetic alteration in exon 9 and the third had a mutation in exon 8. These germline mutations occurred in the C-terminus of the dpc4 gene, similar to most published mutations. One patient exhibited a non-sense mutation (codon 388), which changed a glutamine codon (CAG) to a stop codon (TAG). The second patient harbored a mis-sense mutation (codon 390), causing a non-conservative amino-acid change . The third patient had a mis-sense mutation in exon 8 (codon 361), which altered an arginine codon (CGC) into a histidine codon (CAC).

Adenomatous Polyposis Coli↗

PubMed2000

In vivo gene transfer to the mouse nasal cavity mucosa using a stable cationic lipid emulsion.

We evaluate a new cationic emulsion as a mucosal gene carrier and elucidate the relationship between the transfection efficiency and the stability of the carrier/DNA complex. A cationic lipid emulsion was formulated with soybean oil and 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) as major components and was used to transfer genes to the epithelial cells of the mouse nasal cavity via intranasal instillation. Correlation between the transfection efficiency and the stability of the carrier/DNA complex was investigated by measuring the carrier size changes and by observing the degree of DNA protection against DNase I digestion in the presence of heparin. The cationic emulsion showed at least 3 times better transfection activity than the liposomal carriers in nasal mucosae. The cationic emulsion was stable in the presence of heparin whereas the liposomal carriers became very unstable. Unlike DNA in liposome/DNA complexes, DNA in the emulsion/DNA complex was resistant to heparin exchange and DNase I digestion. The cationic emulsion was more effective in delivering DNA to nasal mucosae than commercially available liposomal carriers. The transfection activities of the lipid carriers in nasal cavity mucosae are in agreement with the stability of the lipid carriers and their complexes with DNA.

Animals↗

PubMed2000

Cloning and expression study of the mouse tetrodotoxin-resistant voltage-gated sodium channel alpha subunit NaT/Scn11a.

We have cloned a tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel alpha subunit from a mouse cDNA library and designated it as NaT. It encodes 1765 amino acid residues and is virtually identical to that of Scn11a, which has been reported recently, except for 40 nt and 14 aa substitutions. The amino acid identity of NaT/Scn11a with rat NaN/SNS2 is 88%. NaT/Scn11a was mapped to mouse chromosome 9F3-F4 by fluorescence in situ hybridization (FISH). While rat NaN/SNS2 has been reported to be expressed specifically in the peripheral sensory neurons, NaT/Scn11a is expressed not only in the peripheral sensory neurons but also in the spinal cord, uterus, testis, ovary, placenta, and small intestine. NaT is detectable in mouse embryos 15 days postcoitus (p.c.), around the phase of organogenesis and gonadal differentiation. These findings demonstrate a unique distribution of NaT/Scn11a and suggest some of its roles in the above-mentioned processes.

Amino Acid Sequence↗

PubMed2000

Identification of a novel human voltage-gated sodium channel alpha subunit gene, SCN12A.

We have cloned a cDNA encoding a novel human voltage-gated sodium channel alpha subunit gene, SCN12A, from human brain. Two alternative splicing variants for SCN12A have been identified. The longest open reading frame of SCN12A encodes 1791 amino acid residues. The deduced amino acid sequence of SCN12A shows 37-73% similarity with various other mammalian sodium channels. The presence of a serine residue (S360) in the SS2 segment of domain I suggests that SCN12A is resistant to tetrodotoxin (TTX), as in the cases of rat Scn10a (rPN3/SNS) and rat Scn11a (NaN/SNS2). SCN12A is expressed predominantly in olfactory bulb, hippocampus, cerebellar cortex, spinal cord, spleen, small intestine, and placenta. Although expression level could not be determined, SCN12A is also expressed in dorsal root ganglia (DRG). Both neurons and glial cells express SCN12A. SCN12A maps to human chromosome 3p23-p21.3. These results suggest that SCN12A is a tetrodotoxin-resistant (TTX-R) sodium channel expressed in the central nervous system and nonneural tissues.

Amino Acid Sequence↗

PubMed2000

Solid-state 87Rb NMR study in powdered RbMnCl3.

Structural phase transition at 290 K and the implication on the intermediate phase above 290 K in powdered RbMnCl3 are observed by using a solid-state 87Rb NMR spectroscopy. Quadrupole coupling constants (e2qQ/h), the asymmetry parameters (eta), and the relative peak intensities for two physically nonequivalent Rb sites, Rb(I) and Rb(II), are determined from nonlinear least-squares fits to the 87Rb NMR powder patterns in the temperature range from 260 to 330 K. Quadrupole coupling constants and the asymmetry parameters are examined for the detection of the phase transition resulting in a significant structural change in the Rb(II) site. In addition, changes in the relative peak intensity between the Rb(I) and Rb(II) sites seem to suggest the existence of an anomalous intermediate phase, which is complemented by the differential scanning calorimetry and X-ray diffraction studies.

Chlorides↗

PubMed2000

Transanally injected triamcinolone acetonide in levator syndrome.

PURPOSE: Several treatments are used for the treatment of levator syndrome, such as rectal massage, biofeedback, and galvanic stimulation. But their effects are inconsistent, and multiple treatment sessions are usually required. Triamcinolone acetonide and lidocaine mixture was injected locally into the tenderest point in levator syndrome under the hypothesis that levator syndrome is caused by tendinitis of pelvic floor musculature. METHODS: A mixture of 40 mg of triamcinolone acetonide and 1 ml of 2 percent lidocaine was injected into the tenderest point transanally in 104 patients (33 males; mean age, 51 years) with levator syndrome from December 1996 to May 1998 at Daehang Clinic. Additional injections were repeated at two-week intervals to a maximum of three injections in cases of poor response. Follow-up was performed prospectively concerning patient's perception of pain level using a visual analog scale. Depending on the response, the patients were classified into four groups: pain-free, good, fair, and no response. More than 50 percent pain reduction was classified as "good," and less than 49 percent reduction as "fair." RESULTS: The injection regions, where the tenderest points were identified on digital rectal compression, were left anterior anal canal in 71.2 percent of patients, right anterior in 3.8 percent of patients, and posterior in 25 percent of patients. The results of treatment were as follows: at three months after injection, response was classified as pain-free in 36.8 percent of patients, good in 35 percent of patients, fair in 19.5 percent of patients, and no response in 8.7 percent of patients; at six months the response was pain-free in 30.1 percent of patients, good in 46.5 percent of patients, fair in 18.2 percent of patients, and no response in 5.2 percent of patients. Most patients, except 8.7 percent at three months and 5.2 percent at six months, experienced treatment benefits. There were no complications during the follow-up periods. CONCLUSION: Transanal injection of triamcinolone acetonide and lidocaine mixture into the tenderest point is such a simple, safe, and very effective modality that it can be recommended as a primary therapy for levator syndrome.

Adolescent↗

PubMed2000

A cationic lipid emulsion/DNA complex as a physically stable and serum-resistant gene delivery system.

PURPOSE: To develop a non-viral gene delivery system in the form of an oil-in-water (o/w) lipid emulsion. METHOD: Cationic lipid emulsions were formulated with soybean oil, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) as a cationic emulsifier and other co-emulsifiers. The physical characteristics of the lipid emulsion and the emulsion/DNA complex were determined. The in vitro transfection efficiency of the emulsion/DNA complex was determined in the presence of up to 90% serum. RESULTS: The average droplet size and zeta potential of emulsions were ca. 180 nm and ca. +50 mV, respectively. Among the emulsions, a stable formulation was selected to form a complex with a plasmid DNA encoding chloramphenicol acetyltransferase. By increasing the ratio of emulsion to DNA. zeta-potential of the emulsion/DNA complex increased monotonously from negative to positive without any changes in the complex size. The complex was stable against DNase I digestion and an anionic poly-L-aspartic acid (PLAA). The complex delivered DNA into the cells successfully, and the transfection efficiency was not affected by complex formation time from 20 min to 2 h. More importantly, the cationic lipid emulsion facilitated the transfer of DNA in the presence of up to 90% serum. CONCLUSIONS: The cationic lipid emulsion/DNA complex has physical stability and serum resistant properties for gene transfer.

Animals↗