Biomedical subjects

J K Suh

Publications and source records attributed to J K Suh.

At least 19 recordsLinked to original sources

PubMed2003

A double-blind, randomised- placebo, controlled, parallel group, multicentre, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea.

The efficacy and safety of sildenafil was evaluated in a randomiSed, double-blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months duration. A total of 133 patients were randomised at six centres in Korea to receive either sildenafil (50 mg initially, increased if necessary to l00 mg or decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual activity for a period of 8 weeks. At the end of this time, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the International Index of Erectile Function (IIEF) scale, (2) the percentage of successful intercourse attempts, and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P&<0.0001). Treatment-related adverse events occurred in 56.1% of patients receiving sildenafil and 20.9% receiving placebo. The most common adverse events with sildenafil were vasodilatation (flushing), headache and abnormalities in colour vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in this population of Korean men appears similar to that reported in other studies in western populations.

Adult↗

PubMed2001

Identification of a negative Cis-regulatory element and multiple DNA binding proteins that inhibit transcription of the transforming growth factor-beta type II receptor gene.

Expression of the transforming growth factor-beta type II receptor (TGF-beta RII) is highly regulated and is a critical determinant of the cellular response to TGF-beta. Previous analysis of the promoter region for the TGF-beta RII gene introduced the possible existence of a negative regulatory element (NRE) upstream adjacent to the core promoter region (Bae et al., 1995. J. Biol. Chem. 270, 29460-29468). We have confirmed the presence of a strong NRE located between base pairs -100 and -67 relative to the transcription start site. Utilizing DNA transfection techniques and a series of synthesized oligonucleotide promoter fragments, we have shown that this NRE is active in a variety of cell lines. Electrophoretic mobility shift assays have revealed the presence of multiple DNA binding proteins specifically interacting with the NRE. At least three distinct protein complexes are variably present depending on the specific cell line examined, and mutational analysis of the NRE has identified a ten-base pair recognition sequence which is shared by all three complexes. This palindromic sequence has not been previously reported and does not share homology with any known transcription factor consensus sequences. When inserted into an E4Delta heterologous promoter construct, the NRE binding sequence failed to inhibit either basal or activated transcription of the target gene, indicating that the NRE does not act as a general repressor but may specifically operate within the context of the TGF-beta RII core promoter.

Animals↗

PubMed2001

A cross-validation of the biphasic poroviscoelastic model of articular cartilage in unconfined compression, indentation, and confined compression.

The biphasic poroviscoelastic (BPVE) model was curve fit to the simultaneous relaxation of reaction force and lateral displacement exhibited by articular cartilage in unconfined compression (n=18). Model predictions were also made for the relaxation observed in reaction force during indentation with a porous plane-ended metal indenter (n=4), indentation with a nonporous plane ended metal indenter (n=4), and during confined compression (n=4). Each prediction was made using material parameters resulting from curve fits of the unconfined compression response of the same tissue. The BPVE model was able to account for both the reaction force and the lateral displacement during unconfined compression very well. Furthermore, model predictions for both indentation and confined compression also followed the experimental data well. These results provide substantial evidence for the efficacy of the biphasic poroviscoelastic model for articular cartilage, as no successful cross-validation of a model simulation has been demonstrated using other mathematical models.

Animals↗

PubMed2001

An in situ calibration of an ultrasound transducer: a potential application for an ultrasonic indentation test of articular cartilage.

A change in mechanical properties of articular cartilage would be considered one of the most reliable signs of cartilage degeneration. While an indentation method has the potential to measure the cartilage properties in vivo, an accurate measurement of cartilage thickness in situ is technically difficult. An ultrasound transducer has often been used to measure the cartilage thickness. However, its accuracy is limited by the lack of an accurate measurement of the ultrasound speed of cartilage, for the ultrasound speed varies according to the pathological conditions of the tissue. Therefore, the objective of this study is to develop an in situ calibration method of predicting the true ultrasound speed of cartilage and thus allow the ultrasound transducer to measure the thickness of the tissue with great accuracy. By simultaneously implementing an indentation testing protocol using the ultrasound transducer as an indenter, this method can also provide an indentation stiffness measurement of cartilage. The feasibility of the proposed method was examined using normal and proteoglycan-depleted cartilage specimens. It was found that the true ultrasound speed measured by the in situ calibration method was sensitive to the proteoglycan depletion (1735+/-35 m/s for normal, and 1598+/-28 m/s for proteoglycan-depleted cartilage), and that the measured cartilage thickness was consistently accurate regardless of the tissue condition. The measured indentation stiffness of articular cartilage was also sensitive to the tissue condition. Thus, this study demonstrates that the proposed ultrasonic indentation technique can be used to accurately identify the abnormality of articular cartilage in situ.

Animals↗

PubMed2001

Microscopic and macroscopic approaches of Cu(II) removal by FSM-16.

The removal of Cu(II) by a mesoporous material, FSM-16, was studied using electron paramagnetic resonance (EPR) spectroscopy and surface complexation modeling (SCM). Free copper ions, adsorbed and precipitated Cu(II) species were qualitatively identified by in situ EPR spectroscopy of Cu-FSM-16 suspensions at room temperature and at 77 K. In addition, the adsorbed species was identified as a Cu(II) species with an axial symmetry from an analysis of the EPR spectra of "dry" Cu-FSM-16 at 77 K. On the basis of the EPR results, the removal of Cu(II) as a function of pH under various experimental conditions was successfully simulated by assuming two removal mechanisms such as surface complexation and surface precipitation. In the acidic pH range (< pH 6), free copper ions were predominant, and surface complexed then surface precipitated species became dominant as the pH increased.

Adsorption↗

PubMed2001

Biphasic poroviscoelastic simulation of the unconfined compression of articular cartilage: II--Effect of variable strain rates.

This study investigated the abilities of the linear biphasic poroviscoelastic (BPVE) model and the linear biphasic poroelastic (BPE) model to simulate the effect of variable ramp strain rates on the unconfined compression stress relaxation response of articular cartilage. Curve fitting of experimental data showed that the BPVE model was able to successfully account for the ramp strain rate-dependent viscoelastic behavior of articular cartilage under unconfined compression, while the BPE model was able to account for the complete viscoelastic response at a slow strain rate, but only the long-term viscoelastic response at faster strain rates. We concluded that the short-term viscoelastic behavior of articular cartilage, when subjected to a fast ramp strain rate, is primarily governed by a fluid flow-independent (intrinsic) viscoelastic mechanism, whereas the long-term viscoelastic behavior is governed by a fluid flow-dependent (biphasic) viscoelastic mechanism. Furthermore, a linear viscoelastic representation of the solid stress was found to be a valid model assumption for the simulation of ramp strain rate-dependent relaxation behaviors of articular cartilage within the range of ramp strain rates investigated.

Animals↗

PubMed2001

Biphasic poroviscoelastic simulation of the unconfined compression of articular cartilage: I--Simultaneous prediction of reaction force and lateral displacement.

This study investigated the ability of the linear biphasic poroelastic (BPE) model and the linear biphasic poroviscoelastic (BPVE) model to simultaneously predict the reaction force and lateral displacement exhibited by articular cartilage during stress relaxation in unconfined compression. Both models consider articular cartilage as a binary mixture of a porous incompressible solid phase and an incompressible inviscid fluid phase. The BPE model assumes the solid phase is elastic, while the BPVE model assumes the solid phase is viscoelastic. In addition, the efficacy of two additional models was also examined, i.e., the transversely isotropic BPE (TIBPE) model, which considers transverse isotropy of the solid matrix within the framework of the linear BPE model assumptions, and a linear viscoelastic solid (LVE) model, which assumes that the viscoelastic behavior of articular cartilage is solely governed by the intrinsic viscoelastic nature of the solid matrix, independent of the interstitial fluid flow. It was found that the BPE model was able to accurately account for the lateral displacement, but unable to fit the short-term reaction force data of all specimens tested. The TIBPE model was able to account for either the lateral displacement or the reaction force, but not both simultaneously. The LVE model was able to account for the complete reaction force, but unable to fit the lateral displacement measured experimentally. The BPVE model was able to completely account for both lateral displacement and reaction force for all specimens tested. These results suggest that both the fluid flow-dependent and fluid flow-independent viscoelastic mechanisms are essential for a complete simulation of the viscoelastic phenomena of articular cartilage.

Animals↗

PubMed2001

Distal anterior cerebral artery aneurysms: clinical features and surgical outcome.

Aneurysms of the distal anterior cerebral artery (DACA) are rare and their surgical treatments present some unique difficulties from a technical standpoint. In this report, we presented our experiences of cases with DACA aneurysms, and analyzed the clinical features and prognostic factors affecting the final outcomes. Among 770 cases of intracranial aneurysms operated from 1990 to 1998, 19 cases of DACA aneurysms (2.5%) were studied retrospectively. The characteristic findings were female preponderance (M:F = 1:2.8), common multiple aneurysms (57.9%), and frequent intracerebral hemorrhage (ICH) on initial brain CT scan (42.1%). All patients were operated via interhemispheric approach. Intraoperative aneurysmal rupture was developed only in 3 cases (15.8%), and had no relationship with the final outcome Fifteen out of 19 patients (78.9%) showed favorable outcome with a mortality rate of 5.3%. The follow-up data suggest that the initial ICH on brain CT scan portend a poor prognosis.

Adult↗

PubMed2000

Redox regulation of yeast flavin-containing monooxygenase.

The flavin-dependent monooxygenase from yeast (yFMO) oxidizes biological thiols such as cysteine, cysteamine, and glutathione. The enzyme makes a major contribution to the pools of oxidized thiols that, together with reduced glutathione from glutathione reductase, create the optimum cellular redox environment. We show that the activity of yFMO, as a soluble enzyme or in association with the ER membrane of microsomal fractions, is correlated with the redox potential. The enzyme is active under conditions normally found in the cytoplasm, but is inhibited as GSSG accumulates to give a redox potential similar to that found in the lumen of the ER. Site-directed mutations show that Cys 353 and Cys 339 participate in the redox regulation. Cys 353 is the principal residue in the redox-sensitive switch. We hypothesize that it may initiate formation of a mixed disulfide that is partially inhibitory to yFMO. The mixed disulfide may exchange with Cys 339 to form an intramolecular disulfide bond that is fully inhibitory.

Base Sequence↗

PubMed2000

GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis.

The quality of articular cartilage engineered using a cell-polymer construct depends, in part, on the chemical composition of the biomaterial and whether that biomaterial can support the chondrocytic phenotype. Acknowledging the supportive influence of tissue-specific matrix molecules on the chondrocytic phenotype, we have combined chondroitin sulfate-A (CSA) and chitosan, a glycosaminoglycan (GAG) analog, to develop a novel biomaterial to support chondrogenesis. Chitosan is a polycationic repeating monosaccharide of beta-1,4-linked glucosamine monomers with randomly located N-acetyl glucosamine units. Chitosan may be combined with the polyanionic CSA such that ionic crosslinking results in hydrogel formation. Bovine primary articular chondrocytes, when seeded onto a thin layer of CSA-chitosan, form discrete, focal adhesions to the material and maintain many characteristics of the differentiated chondrocytic phenotype, including round morphology, limited mitosis, collagen type II, and proteoglycan production. Our findings suggest CSA-chitosan may be well suited as a carrier material for the transplant of autologous chondrocytes or as a scaffold for the tissue engineering of cartilage-like tissue.

Animals↗

PubMed2000

Yeast flavin-containing monooxygenase is induced by the unfolded protein response.

Flavin-containing monooxygenase from yeast (yFMO) carries out the O(2)- and NADPH-dependent oxidation of biological thiols, including oxidizing glutathione to glutathione disulfide. FMO provides a large fraction of the oxidizing necessary for proper folding of disulfide bond-containing proteins; deletion of the enzyme reduces proper folding of endogenous carboxypeptidase Y by about 40%. The enzyme is not essential to cell viability because other enzymes can generate a significant fraction of the oxidizing equivalents required by the cell. However, yFMO is vital to the yeast response to reductive stress. FMO1 deletion mutants grow poorly under reductive stress, and carboxypeptidase Y activity is less than 10% of that in a stressed wild type. The FMO1 gene appears to be under control of an unfolded protein response element and is inducible by factors, such as reductive stress, that elicit the unfolded protein response. Reductive stress can increase yFMO activity at least 6-fold. This increased activity allows the cell to process endogenous disulfide bond-containing proteins and also to allow correct folding of disulfide-bonded proteins expressed from multicopy plasmids. The unfolded protein response is mediated by the Hac1p transcription factor that mediates virtually all of the induction of yFMO triggered by exogenous reducing agents.

Basic-Leucine Zipper Transcription Factors↗

PubMed2000

Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review.

Once damaged, articular cartilage has very little capacity for spontaneous healing because of the avascular nature of the tissue. Although many repair techniques have been proposed over the past four decades, none has sucessfully regenerated long-lasting hyaline cartilage tissue to replace damaged cartilage. Tissue engineering approaches, such as transplantation of isolated chondrocytes, have recently demonstrated tremendous clinical potential for regeneration of hyaline-like cartilage tissue and treatment of chondral lesions. As such a new approach emerges, new important questions arise. One of such questions is: what kinds of biomaterials can be used with chondrocytes to tissue-engineer articular cartilage? The success of chondrocyte transplantation and/or the quality of neocartilage formation strongly depend on the specific cell-carrier material. The present article reviews some of those biomaterials, which have been suggested to promote chondrogenesis and to have potentials for tissue engineering of articular cartilage. A new biomaterial, a chitosan-based polysaccharide hydrogel, is also introduced and discussed in terms of the biocompatibility with chondrocytes.

Animals↗

PubMed2000

Chronic subdural hematoma: evaluation of the clinical significance of postoperative drainage volume.

OBJECT: A wide variation in postoperative drainage volumes is observed during treatment of chronic subdural hematoma (CSDH) with twist-drill or burr-hole craniostomy and closed-system drainage. In this study the authors investigate the causes of the variation, the clinical significance thereof, and its influence on treatment outcome. METHODS: A total of 175 cases were investigated between January 1991 and December 1997. Of these, 145 patients had surgery for CSDH, of whom 30 had bilateral lesions. The cases of CSDH were divided into five subtypes (low-density, isodense, high-density, mixed-density, and layering types) on the basis of the brain computerized tomography (CT) findings. Burr-hole craniostomies with closed-system drainage were performed in all patients and the drainage was maintained for 5 days, during which daily amounts of fluid were measured. The mean drainage volume over 5 days was 320 ml, with the largest volume (413 ml) seen in the low-density type and the smallest (151 ml) in the mixed-density type of CSDH. There were recurrences in six patients (seven instances, 4%). The mixed-density type had the highest recurrence rate (8.6%), whereas there was no recurrence for the low-density type. There were no recurrences in 81 patients in whom the total drainage volumes for 5 days were more than 200 ml, but there were recurrences in six (seven instances) of 94 patients in whom the total drainage volume was less than 200 ml. CONCLUSIONS: The postoperative drainage volumes varied greatly because of differences in the outer membrane permeability of CSDH, and such variation seems to be related to the findings on the CT scans obtained preoperatively. Patients with CSDH in whom there is less postoperative drainage than expected should be carefully observed, with special attention paid to the possibility of recurrence.

Adult↗

PubMed1999

Lysine 219 participates in NADPH specificity in a flavin-containing monooxygenase from Saccharomyces cerevisiae.

The flavin-containing monooxygenase from Saccharomyces cerevisiae (yFMO) uses NADPH and O(2) to oxidize thiol containing substrates such as GSH and thereby generates the oxidizing potential for the ER. The enzyme uses NADPH 12 times more efficiently than NADH. Amino acid sequence analysis suggests that Lys 219 and/or Lys 227 may act as counterions to the 2' phosphate of NADPH and to help determine the preference for pyridine nucleotides. Site directed mutations show that Lys 219 makes the greater contribution to cosubstrate recognition. Conversion of Lys 219 to Ala reduces NADPH dependent activity 90-fold, but has no effect on NADH-dependent activity. Conversion of Lys 227 to Ala reduces NADPH-dependent activity fivefold and NADH-dependent activity threefold. Dissociation constants for NADP(+) to oxidized yFMO were measured spectroscopically. K(d) is 12 microM for the wild-type enzyme and 243 microM for the K219A mutant, consistent with the role of Lys 219 in pyridine nucleotide binding.

Amino Acid Sequence↗

PubMed1999

Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene.

STUDY DESIGN: In vivo studies using a rabbit model to determine the biologic effects of direct, adenovirus-mediated transfer of a therapeutic gene to the intervertebral disc. OBJECTIVES: 1) To deliver an exogenous therapeutic gene to rabbit lumbar intervertebral discs in vivo, 2) to quantify the resulting amount of gene expression, and 3) to determine the effect on the biologic activity of the discs. SUMMARY OF BACKGROUND DATA: Although growth factors such as transforming growth factor beta 1 appear to have promising therapeutic properties, there currently is no practical method for sustained delivery of exogenous growth factors to the disc for the management of certain chronic types of disease (e.g., disc degeneration). A possible solution is to modify the disc cells genetically through gene transfer such that the cells manufacture the desired growth factors endogenously on a continuous basis. METHODS: Saline, with or without virus, was injected directly into lumbar discs of 22 skeletally mature female New Zealand white rabbits. Group 1 (n = 11) received the adenovirus construct Ad/CMV-hTGF beta 1 containing the therapeutic human transforming growth factor beta 1-encoding gene. Group 2 (n = 6) received adenovirus containing the luciferase marker gene. Group 3 (n = 5) received saline only. The rabbits were killed 1 week after injection. Immunohistochemical staining for human transforming growth factor beta 1 was performed on the disc tissues of one rabbit from Group 1. Nucleus pulposus tissues from the remaining rabbits were cultured in serumless medium. Bioassays were performed to determine human transforming growth factor beta 1 production and proteoglycan synthesis. RESULTS: Discs injected with Ad/CMV-hTGF beta 1 exhibited extensive and intense positive immunostaining for transforming growth factor beta 1. The nucleus pulposus tissues from the discs injected with Ad/CMV-hTGF beta 1 exhibited a 30-fold increase in active transforming growth factor beta 1 production, and a 5-fold increase in total (active + latent) transforming growth factor beta 1 production over that from intact control discs (P < 0.05). Furthermore, these tissues exhibited a 100% increase in proteoglycan synthesis compared with intact control tissue, which was statistically significant (P < 0.05). CONCLUSIONS: The results of this study suggest that the intervertebral disc is an appropriate site for adenovirus-mediated transfer of exogenous genes and subsequent production of therapeutic growth factors. Gene therapy therefore may have useful applications for study of the basic science of the intervertebral disc and for clinical management of degenerative disc disease.

Adenoviridae↗

PubMed1999

Yeast flavin-containing monooxygenase generates oxidizing equivalents that control protein folding in the endoplasmic reticulum.

The flavin-containing monooxygenase from yeast (yFMO) catalyzes the O2- and NADPH-dependent oxidations of biological thiols, including oxidation of glutathione to glutathione disulfide (GSSG). Glutathione and GSSG form the principle redox buffering system in the cell, with the endoplasmic reticulum (ER) being more oxidizing than the cytoplasm. Proper folding of disulfide-bonded proteins in the ER depends on an optimum redox buffer ratio. Here we show that yFMO is localized to the cytoplasmic side of the ER membrane. We used a gene knockout strain and expression vectors to show that yFMO has a major effect on the generation of GSSG transported into the ER. The enzyme is required for the proper folding, in the ER, of test proteins with disulfide bonds, whereas those without disulfide bonds are properly folded independently of yFMO in the ER or in the cytoplasm.

Cell Compartmentation↗

PubMed1999

Intermittent sub-ambient interstitial hydrostatic pressure as a potential mechanical stimulator for chondrocyte metabolism.

OBJECTIVE: Experimental findings have suggested that the metabolic activities of articular cartilage can be influenced by mechanical stimuli. Our mathematical analysis predicted that cyclic compressive loading may create periods of intermittent sub-ambient hydrostatic pressure within the cartilage extracellular matrix. Based on this mathematical analysis, the present study was aimed to investigate whether the intermittent sub-ambient hydrostatic pressure, created in the cartilage extracellular matrix during cyclic compression, has a stimulative effect on the biosynthesis of chondrocytes. METHOD: In order to test this hypothesis, the present study developed a custom-designed sub-ambient pressure generator to subject a monolayer culture of chondrocytes to an intermittent sub-ambient pressure. Using this pressure generator, the monolayer chondrocyte culture system was analyzed for 35S-sulfate and 3H-proline incorporation rates for biosynthesis of proteoglycan and collagenous/noncollagenous protein molecules, respectively. Northern analyses for aggrecan and type II collagen mRNAs were also performed. RESULTS: It was found that the intermittent sub-ambient pressure produced a 40% increase in proteoglycan and a 17% increase in non-collagenous protein synthesis during the pressurization period (P < 0.05). The collagenous protein synthesis was not affected by the intermittent sub-ambient pressure regimen used in this study. After the intermittent sub-ambient pressurization, the metabolic activities of the chondrocytes returned to normal (control level). The intermittent sub-ambient pressure also produced an increase in the mRNA signals for aggrecan. Therefore, we conclude that intermittent sub-ambient pressure may be one of the potential mechanical stimulators of chondrocytes in articular cartilage during dynamic compression.

Aggrecans↗

PubMed1998

Adenovirus-mediated gene transfer to nucleus pulposus cells. Implications for the treatment of intervertebral disc degeneration.

STUDY DESIGN: In vitro and in vivo studies using a rabbit model were performed to determine the feasibility of adenovirus-mediated gene transfer to the intervertebral disc. OBJECTIVES: This study was conducted to determine whether it is possible to transfer genes to cells within the intervertebral disc by direct injection of an adenovirus and to determine the duration of gene expression obtained by this method. SUMMARY OF BACKGROUND DATA: Although growth factors have the potential to stimulate the regeneration of nucleus pulposus, sustained delivery of growth factors to a degenerated disc is clinically unfeasible with present technology. Novel approaches such as gene transfer should be investigated as possible solutions to this problem. METHODS: The lacZ marker gene was used to evaluate gene delivery to cells within intervertebral discs. For the in vitro study, cell cultures were established from the nucleus pulposus tissue of New Zealand white rabbits and infected with an adenovirus encoding the lacZ gene (Ad-lacZ). For the in vivo study, the anterior aspects of lumbar intervertebral discs were surgically exposed, and Ad-lacZ in saline solution was directly injected into the nucleus pulposus. An equal volume of saline only was injected into control discs. Expression of the transferred gene was detected by staining with 5-bromo-4-chloro-3-indolyl-beta-galactosidase (X-Gal). RESULTS: The in vitro experiments confirmed that nucleus pulposus cells were efficiently transduced by an adenoviral vector carrying the lacZ gene. In vivo injection of Ad-lacZ into the nucleus pulposus resulted in the transduction of a considerable number of cells. Marker gene expression in vivo persisted at an apparently undiminished level for at least 12 weeks. No staining was noted in control discs. CONCLUSIONS: The results show the feasibility of adenovirus-mediated gene transfer to the intervertebral disc. Expression of the marker gene persisted at least 12 weeks in vivo. This successful demonstration of exogenous gene transfer to the disc and sustained, long-term expression suggests that the adenoviral vector may be suitable for delivery of appropriate genes to the disc for the treatment of spinal disorders.

Adenoviridae↗