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Biomedical subjects

S K Chung

Publications and source records attributed to S K Chung.

At least 37 records · Page 2Linked to original sources
PubMed2000

Decentration and tilt: silicone multifocal versus acrylic soft intraocular lenses.

PURPOSE: To compare differences in decentration and tilt between a silicone multifocal and an acrylic intraocular lens (IOL) by evaluating postoperative changes. SETTING: Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea. METHODS: Forty eyes of 20 patients with IOL implantation were randomized into 2 groups according to IOL type: 3-piece silicone multifocal IOL or 3-piece acrylic IOL. All lenses were implanted in the capsular bag through a clear corneal incision after continuous curvilinear capsulorhexis and phacoemulsification. The amount of the decentration and the degree of the tilt of each IOL were measured using the EAS-1000 anterior eye segment analysis system 1 day and 1 and 2 months after surgery. RESULTS: No significant difference in decentration and tilt was found among the 3 follow-ups or between lens types. CONCLUSION: Neither IOL decentration nor tilt showed significant progression up to 2 months in eyes with a silicone multifocal or acrylic IOL when the IOLs were placed properly in the capsular bag. The amount of decentration and tilt was similar between lens types.

Acrylic Resins↗
PubMed2000

Decentration, tilt, and near vision of the array multifocal intraocular lens.

PURPOSE: To study the periodic changes in decentration, tilt, and near vision in eyes with the Array(R) multifocal intraocular lens (IOL). SETTING: Department of Ophthalmology, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. METHOD: This study comprised 20 eyes of 10 patients older than 60 years who had binocular cataract and bilateral implantation of the Array multifocal IOL. Mean patient age was 66.0 years (range 60 to 75 years). After a clear corneal incision and continuous curvilinear capsulorhexis were made, each eye had phacoemulsification and in-the-bag IOL implantation. The amount of IOL decentration and degree of tilt were evaluated using the EAS-1000 anterior eye segment analysis system 1 day and 1 and 2 months postoperatively. Near and far visual acuities were measured at the same examinations. RESULTS: No statistically significant differences were observed in decentration (P =.13) or tilt (P =.32) throughout the follow-up. Mean uncorrected distance visual acuity was 0.68 +/- 0.27 (SD), and mean uncorrected near acuity was 0.49 +/- 0.15 2 months postoperatively. Uncorrected distance acuity better than 0.5 was achieved in 14 eyes (77.8%), in which the mean uncorrected distance acuity was 0.80 +/- 0.18 and the mean uncorrected near acuity was 0. 53 +/- 0.14 2 months postoperatively. CONCLUSIONS: Tilt and decentration of the Array multifocal IOL showed no significant progression up to 2 months after implantation. For near acuity, the Array IOL may be an effective aid.

Aged↗
PubMed2000

Design and synthesis of potential inhibitors of the ergosterol biosynthesis as antifungal agents.

A series of azolylmethyloxolane derivatives with modified sterol side-chain structures, designed as potential dual functional inhibitors of cytochrome P450 14alpha-demethylase (14DM) and delta24-sterol methyltransferase (24-SMT) based on the common characteristic features of 24-aminosterols and azole antifungal agents, were synthesized and evaluated for their antifungal activities and inhibitory activities of 14DM and 24-SMT. Among these compounds, imidazolylmethyloxolane derivatives 28a and 28b showed potent in vitro antifungal activities comparable to those of itraconazole. However, the in vitro bioactivities have not been linearly translated into in vivo protection data for some unknown reasons.

Administration, Oral↗
PubMed2000

Human intravenous immunoglobulin preparation and virus inactivation by pasteurization and solvent detergent treatment.

Human intravenous immunoglobulin (IVIG) solutions were prepared by two different methods and compared to each other. The crude immunoglobulin fraction obtained from Cohn-Oncley fractionation of plasma was further purified and subjected to virus inactivation, either by polyethylene glycol precipitation and pasteurization at 60 degrees C for 10 hours, or by ion exchange chromatography and solvent/detergent treatment. The final preparations, formulated in 5% immunoglobulin solutions were characterized by in vitro analyses of biochemical and biological properties and compared with the samples of other manufacturer's IVIG solution products. The critical properties evaluated in this study were purity, molecular intactness, and the biological functions such as Fc function and anticomplementary activity. Virus inactivation and removal by processing steps and by deliberate virucidal steps, as described above, were tested on various human pathogenic viruses, such as human immunodeficiency and experimental model viruses. The tested viruses were successfully inactivated and removed. We conclude that the intravenous immunoglobulins prepared by two different methods, as described above, provide an equivalent viral safety and quality.

Antibodies↗
PubMed2000

Aldose reductase-deficient mice develop nephrogenic diabetes insipidus.

Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus.

Aldehyde Reductase↗
PubMed2000

Overexpression of Na(+)-dependent myo-inositol transporter gene in mouse lens led to congenital cataract.

PURPOSE: Maintaining appropriate osmotic pressure is essential for maintaining lens transparency. This study was performed to investigate whether high levels of myo-inositol, one of the major organic osmolytes in the lens, would lead to cataract development. METHODS: Transgenic mouse lines carrying the bovine Na(+)-dependent myo-inositol transporter (bSMIT) cDNA under the control of the mouse alphaA-crystallin promoter were generated. RESULTS. Increased bSMIT expression was accompanied by increased myo-inositol level in the lens and increased uptake of (3H) myo-inositol by the lens in culture. The transgenic mice developed observable cataract under normal rearing conditions beginning at 2 to 8 weeks of age, and the severity of cataract development was correlated to the level of bSMIT gene expression and lens myo-inositol accumulation. For transgenic mouse line 3352, heterozygous mice did not develop cataract, whereas homozygous ones did. Prenatal feeding of heterozygous 3352 mice with high myo-inositol diet led to cataract development, indicating that cataract development was not merely due to a nonspecific effect of SMIT overexpression. Introducing aldose reductase overexpressing transgene into heterozygous 3352 mice also led to cataract development, indicating that this type of cataract is primarily due to osmotic stress. CONCLUSIONS: The present results indicate that high levels of myo-inositol and sorbitol in the lens contribute to cataract development. This is a useful model to study the role of osmotic stress in cataractogenesis during lens development.

Aldehyde Reductase↗
PubMed1999

Glucose-dependent insulinotropic polypeptide gene expression in the stomach: revealed by a transgenic mouse study, in situ hybridization and immunohistochemical staining.

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in stimulating insulin release in the pancreas as well as inhibiting gastric acid secretion in the stomach. GIP has been found in specific endocrine cells located in the mucosal layer of the small intestine and in the submandibular salivary gland. In this study, the tissue-specific expression of GIP guided by 1.2 kb of the human GIP (hGIP) gene 5' flanking region was investigated by a transgenic mouse approach. A chimeric promoter-reporter gene construct linking the 5'-flanking region of the hGIP gene with the thymidine kinase gene of the herpes simplex virus was introduced into the genomes of mice by microinjection. By reverse transcriptase-PCR (RT-PCR) and thymidine kinase assays, transgene expression was found in the stomach and pancreas. The enzyme activity detected in the stomach was about 6-fold higher than that found in the pancreas, suggesting that GIP may be expressed in the stomach. This observation is supported by RT-PCR studies since both human and mouse GIP transcripts are detected in the stomach and small intestine. In addition, distinct GIP-producing cells were identified in both tissues in mouse by in situ hybridization and immunohistochemical staining. Taken together, our data demonstrate for the first time that GIP is expressed in human and mouse stomach.

Amino Acid Sequence↗
PubMed1999

Practical synthesis of all inositol stereoisomers from myo-inositol.

Synthesis of six inositol stereoisomers was successfully carried out via conduritol intermediates prepared from myo-inositol. Dihydroxylation and epoxidation followed by ring opening of the conduritol B, C and F derivatives gave epi-, allo-, muco-, neo-, DL-chiro- and scyllo-inositol. The cis-inositol derivative, which may not be prepared by this approach, was synthesized in 5 steps via 2-O-benzoyl-myo-inositol orthoformate as the key intermediate.

Hydroxylation↗
PubMed1999

Inositol 1,3,4-trisphosphate acts in vivo as a specific regulator of cellular signaling by inositol 3,4,5,6-tetrakisphosphate.

Ca2+-activated Cl- channels are inhibited by inositol 3,4,5, 6-tetrakisphosphate (Ins(3,4,5,6)P4) (Xie, W., Kaetzel, M. A., Bruzik, K. S., Dedman, J. R., Shears, S. B., and Nelson, D. J. (1996) J. Biol. Chem. 271, 14092-14097), a novel second messenger that is formed after stimulus-dependent activation of phospholipase C (PLC). In this study, we show that inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) is the specific signal that ties increased cellular levels of Ins(3,4,5,6)P4 to changes in PLC activity. We first demonstrated that Ins(1,3,4)P3 inhibited Ins(3,4,5,6)P4 1-kinase activity that was either (i) in lysates of AR4-2J pancreatoma cells or (ii) purified 22,500-fold (yield = 13%) from bovine aorta. Next, we incubated [3H]inositol-labeled AR4-2J cells with cell permeant and non-radiolabeled 2,5,6-tri-O-butyryl-myo-inositol 1,3, 4-trisphosphate-hexakis(acetoxymethyl) ester. This treatment increased cellular levels of Ins(1,3,4)P3 2.7-fold, while [3H]Ins(3, 4,5,6)P4 levels increased 2-fold; there were no changes to levels of other 3H-labeled inositol phosphates. This experiment provides the first direct evidence that levels of Ins(3,4,5,6)P4 are regulated by Ins(1,3,4)P3 in vivo, independently of Ins(1,3,4)P3 being metabolized to Ins(3,4,5,6)P4. In addition, we found that the Ins(1, 3,4)P3 metabolites, namely Ins(1,3)P2 and Ins(3,4)P2, were >100-fold weaker inhibitors of the 1-kinase compared with Ins(1,3,4)P3 itself (IC50 = 0.17 microM). This result shows that dephosphorylation of Ins(1,3,4)P3 in vivo is an efficient mechanism to "switch-off" the cellular regulation of Ins(3,4,5,6)P4 levels that comes from Ins(1,3, 4)P3-mediated inhibition of the 1-kinase. We also found that Ins(1,3, 6)P3 and Ins(1,4,6)P3 were poor inhibitors of the 1-kinase (IC50 = 17 and >30 microM, respectively). The non-physiological trisphosphates, D/L-Ins(1,2,4)P3, inhibited 1-kinase relatively potently (IC50 = 0.7 microM), thereby suggesting a new strategy for the rational design of therapeutically useful kinase inhibitors. Overall, our data provide new information to support the idea that Ins(1,3,4)P3 acts in an important signaling cascade.

Animals↗
PubMed1999

Synergistic effect of optic and peripheral nerve grafts on sprouting of axon-like processes of axotomized retinal ganglion cells in adult hamsters.

We investigated the sprouting response of retinal ganglion cells (RGCs) following the transplantation of peripheral nerve (PN) and/or optic nerve (ON) into the vitreous of the eye and the intraorbital transection of the optic nerve in hamsters. Our previous results showed that an intravitreal PN graft could induce sprouting of axon-like processes in axotomized RGCS [3] (Cho, E.Y. and So, K.F., Characterization of the sprouting response of axon-like processes from retinal ganglion cells after axotomy in adult hamsters: a model using intravitreal implantation of a peripheral nerve, J. Neurocytol., 21 (1992) 589-603). In this model, we have examined the effect of intravitreal ON graft on the sprouting of RGCs both following a co-transplantation of PN and ON into the vitreous and transplantation of ON alone. The present results show that sprouting is increased by more than two-fold in retinas having PN and ON grafts than a PN graft alone. However, the ON graft by itself rarely induced sprouting in RGCs. These results suggest that the ON graft enhance the number of RGCs to sprout axon-like processes in the presence of PN graft by exerting a synergistic rather than an additive effect, since ON graft alone did not induce sprouting. In addition, no diffusible inhibitory effect of ON graft on PN induced sprouting was observed.

Age Factors↗
PubMed1999

Estrogen protects against 3-methylindole-induced olfactory loss.

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD). Since estrogen therapy may mitigate the cognitive symptoms of AD, we determined whether 17beta-estradiol (E2) alters the olfactory discrimination performance of female rats exposed to the olfactotoxicant 3-methylindole (3-MI). Twelve ovariectomized rats received daily injections of E2 (1 mg/kg i.p.) in corn oil and 10 received daily injections of corn oil alone. Sensory testing occurred on a near-daily basis throughout a 10-week test period, midway in which a single injection of 3-MI was administered (300 mg/kg i.p.). On each pre- and post-3-MI test day, the rats were required to perform a series of successively more difficult odor discrimination tasks until one was reached where <80% performance was attained. The tasks were between the odor of a 10-4 v/v concentration of ethyl acetate (EA) and the odor of each of six different concentrations of butanol added to the EA (10-4, 10-4.5, 10-5.0, 10-5.5, 10-6.0, 10-6.5 v/v). Following 3-MI treatment, the performance of the E2-treated rats was found to be superior to that of the oil-treated rats and to return more quickly to the pre-3 MI baseline, suggesting that high doses of E2 mitigate 3-MI-induced smell loss in rats. Additional work is needed to determine the physiologic basis of this phenomenon.

Animals↗
PubMed1999

Whole-body and pinhole bone scintigraphic manifestations of Reiter's syndrome: distribution patterns and early and characteristic signs.

The characteristic whole-body and pinhole scintigraphic manifestations of osteo-enthesopathy and arthropathy in Reiter's syndrome (RS) are described, with an emphasis on early diagnosis. We analysed 59 sets of whole-body and pinhole bone scintigrams of 59 patients with RS. The population comprised 47 men and 12 women with an age range from 15 to 53 years (mean=29.4). Bone scintigraphy was carried out 2-2.5 h after intravenous injection of technetium-99m hydroxydiphosphonate using a single-head gamma camera (Siemens Orbiter Model 6601) with a low-energy high-resolution and a 4-mm pinhole collimator for whole-body and pinhole scintigraphy, respectively. In total 262 lesions of osteo-enthesopathy and arthritis were detected on 59 whole-body scintigrams, an incidence of 4.4 lesions per patient. As anticipated, the lesional distribution was asymmetrical: 68% were in the lower limb skeleton and 32% in the axial and upper limb skeleton. Pinhole bone scintigraphy, applied selectively to one region of interest in each case, enabled us to accurately diagnose arthritis and osteo-enthesopathy. It was noteworthy that osteo-enthesopathy, alone or in combination with arthritis, occurred in 78.9%, and had a strong predilection for the foot bones, especially the calcaneus (25. 6%). Pinhole scintigraphy detected enthesopathy in the absence of radiographic alteration in 14.1% of cases and portrayed characteristic signs of RS in 6.9%. Whole-body bone scintigraphy augmented with pinhole scintigraphy was found to be useful in order to panoramically display the systemic involvement pattern, to assess the characteristic bone and articular alterations and to detect early signs of RS.

Adolescent↗
PubMed1999

Ciliary neurotrophic factor promotes the regrowth capacity but not the survival of intraorbitally axotomized retinal ganglion cells in adult hamsters.

Ciliary neurotrophic factor has recently been shown to promote the axonal regrowth of retinal ganglion cells into a peripheral nerve graft following an intracranial transection of the optic nerve (approximately 7 mm from the optic disc). It is unclear whether the enhancement of axonal regrowth by ciliary neurotrophic factor application correlates with the enhancement of survival of retinal ganglion cells and/or the up-regulation of expression of growth-associated protein-43 messenger RNA in retinas. The present study evaluated the regenerative capacity of retinal ganglion cells following intraorbital transection of the optic nerve (approximately 1.5 mm from the optic disc) and the attachment of a peripheral nerve to the ocular stump of the optic nerve. In addition, we have determined the survival of retinal ganglion cells and the expression of growth-associated protein-43 messenger RNA in ciliary neurotrophic factor-treated retinas following optic nerve transection. The results showed that in the ciliary neurotrophic factor-treated retinas, the number of retinal ganglion cells which had regrown axons into a peripheral nerve is about four times more than the control. In the axotomized retinas, ciliary neurotrophic factor initiated sprouting of axon-like processes at 14 and 28 days post-axotomy and up-regulated the expression level of growth-associated protein-43 messenger RNA at 7, 14 and 28 days post-axotomy. However, ciliary neurotrophic factor did not prevent the death of axotomized retinal ganglion cells. We suggest that one possible mechanism for the axonal regeneration of axotomized retinal ganglion cells by ciliary neurotrophic factor could be mediated by the up-regulation of growth-associated protein-43 gene expression and not by increasing the pool of surviving retinal ganglion cells after axotomy.

Animals↗
PubMed1999

Synthesis of all possible regioisomers of scyllo-inositol phosphate.

scyllo-Inositol is the all equatorial stereoisomer of myo-inositol. All possible 12 regioisomers of scyllo-inositol phosphate were synthesized for the first time via a scyllo-inositol benzoate intermediate, which was derived from a myo-inositol derivative. The stereoinversion of myo-inositol into scyllo-inositol was accomplished by Mitsunobu reaction of the vicinal cis-diol. The requisite intermediates, scyllo-inositol benzoates were obtained by benzoyl migration or random benzoylation, and phosphorylated to give scyllo-IPn.

Inositol↗
PubMed1999

Comparisons of genomic structures and chromosomal locations of the mouse aldose reductase and aldose reductase-like genes.

Aldose reductase (AR), best known as the first enzyme in the polyol pathway of sugar metabolism, has been implicated in a wide variety of physiological functions and in the etiology of diabetic complications. We have determined the structures and chromosomal locations of the mouse AR gene (Aldor1) and of two genes highly homologous to Aldor1: the fibroblast growth factor regulated protein gene (Fgfrp) and the androgen regulated vas deferens protein gene (Avdp). The number of introns and their locations in the mouse Aldor1 gene are identical to those of rat and human AR genes and also to those of Fgfrp and Avdp. Mouse Aldor1 gene was found to be located near the Cald1 (Caldesmon) and Ptn (Pleiotropin) loci at the proximal end of chromosome 6. The closely related genes Fgfrp and Avdp were also mapped in this region of the chromosome, suggesting that these three genes may have arisen by a gene duplication event.

Aldehyde Reductase↗
PubMed1999

Recombinant p42IP4, a brain-specific 42-kDa high-affinity Ins(1,3,4,5)P4 receptor protein, specifically interacts with lipid membranes containing Ptd-Ins(3,4,5)P3.

We have recently cloned the cDNA of p42IP4, a membrane-associated and cytosolic inositol (1,3,4,5)tetrakisphosphate receptor protein [Stricker, R., Hülser, E., Fischer, J., Jarchau, T., Walter, U., Lottspeich, F. & Reiser, G. (1997) FEBS Lett. 405, 229-236.] p42IP4 is a protein of 374 amino acids with Mr of 42 kDa. The p42IP4 protein has a zinc finger motif at its N-terminus, followed by two pleckstrin homology domains. To characterize further the biochemical and functional properties of p42IP4, it was expressed as a glutathione-S-transferase fusion protein in Sf9 cells using a recombinant baculovirus vector. The protein was affinity adsorbed on glutathione beads, cleaved from glutathione-S-transferase with the protease factor-Xa and purified on heparin agarose. The recombinant purified protein is active because it shows binding affinities similar to those of the native p42IP4, purified from pig cerebellum or rat brain (Ki for inositol(1,3,4,5)P4 of 4.1 nm and 2.2 nm, respectively). Moreover the ligand specificity of the recombinant protein for various inositol polyphosphates is similar to that of the native protein purified from brain. Importantly, we show here that p42IP4 binds phosphatidylinositol(3,4,5)P3 specifically, as the recombinant protein can associate with lipid membranes (vesicles) containing phosphatidylinositol(3,4,5)P3; this binding occurs in a concentration-dependent manner and is blocked by inositol(1,3,4,5)P4. This specific association and the possibility that endogenous p42IP4 can be converted from a membrane-associated state to a soluble state support the hypothesis that p42IP4 might be redistributed between cellular compartments upon hormonal stimulation.

Animals↗