Biomedical subjects

Y Cho

Publications and source records attributed to Y Cho.

At least 73 records · Page 4Linked to original sources

PubMed1999

Rescue and regrowth of sensory nerves following deafferentation by neurotrophic factors.

Trauma and loss of cochlear inner hair cells causes a series of events that result first in the retraction of the peripheral processes of the auditory nerve, scar formation in the organ of Corti, and over the course of weeks to months (depending on the species) the loss of auditory nerve cell bodies (spiral ganglion cells). Neurotrophic factors play an important role in the mature nervous system as survival factors for maintenance and protection and also can play a role in regrowth. Studies in the cochlea now show that application of exogenous neurotrophic factors can enhance survival of spiral ganglion cells after deafness and induce regrowth of peripheral processes, perhaps by replacing lost endogenous factors. Combinations of factors may be most effective for achieving greatest survival and regrowth. Our studies find that brain-derived neurotrophic factor (BDNF) and glial-line-derived neurotrophic factor (GDNF) are very effective at enhancing spiral ganglion cell survival following deafness from ototoxic drugs or noise. It has also been found that BDNF plus fibroblast growth factor (FGF) is very effective at inducing process regrowth. Electrical stimulation also acts to enhance spiral ganglion cell survival, and the combination of electrical stimulation and neurotrophic factors could prove a most effective intervention.

Aminoglycosides↗

PubMed1999

The inhibitory effect of ambroxol on hypochlorous acid-induced tissue damage and respiratory burst of phagocytic cells.

Ambroxol (100 microM and 1 mM) and the thiols (all 1 mM), glutathione, tiopronin and cysteine, significantly attenuated the myeloperoxidase, H(2)O(2) and Cl(-) system-caused destruction of alpha(1)-antiproteinase and the HOCl-induced destruction of collagen, whereas they did not affect the elastase-induced destruction of collagen. Glutathione, tiopronin and cysteine almost completely decomposed both HOCl and H(2)O(2), while ambroxol up to 1 mM did not show a scavenging action on H(2)O(2). Ambroxol (1 to 100 microM) and 1 mM thiol compounds markedly inhibited the HOCl-induced alteration of elastase activity. Thiol compounds significantly attenuated the HOCl production caused by degraded immunoglobulin G-activated neutrophils. Ambroxol depressed superoxide and H(2)O(2) production induced by degraded immunoglobulin G-activated neutrophils and by lipopolysaccharide-activated alveolar macrophages in a dose-dependent manner. The results show that ambroxol may interfere with oxidative tissue damage and decrease proteolytic tissue destruction by attenuation of oxidative stress-induced inactivation of alpha(1)-antiproteinase through both decomposition of HOCl and inhibition of the respiratory burst in phagocytic cells.

Ambroxol↗

PubMed1999

Structural basis for cold adaptation. Sequence, biochemical properties, and crystal structure of malate dehydrogenase from a psychrophile Aquaspirillium arcticum.

Aquaspillium arcticum is a psychrophilic bacterium that was isolated from arctic sediment and grows optimally at 4 degrees C. We have cloned, purified, and characterized malate dehydrogenase from A. arcticum (Aa MDH). We also have determined the crystal structures of apo-Aa MDH, Aa MDH.NADH binary complex, and Aa MDH.NAD.oxaloacetate ternary complex at 1.9-, 2.1-, and 2.5-A resolutions, respectively. The Aa MDH sequence is most closely related to the sequence of a thermophilic MDH from Thermus flavus (Tf MDH), showing 61% sequence identity and over 90% sequence similarity. Stability studies show that Aa MDH has a half-life of 10 min at 55 degrees C, whereas Tf MDH is fully active at 90 degrees C for 1 h. Aa MDH shows 2-3-fold higher catalytic efficiency compared with a mesophilic or a thermophilic MDH at the temperature range 4-10 degrees C. Structural comparison of Aa MDH and Tf MDH suggests that the increased relative flexibility of active site residues, favorable surface charge distribution for substrate and cofactor, and the reduced intersubunit ion pair interactions may be the major factors for the efficient catalytic activity of Aa MDH at low temperatures.

Adaptation, Physiological↗

PubMed1999

Expression, purification, characterization and crystallization of flap endonuclease-1 from Methanococcus jannaschii.

A gene coding for a protein homologous to the flap endonuclease-1 (FEN-1) was cloned from Methanococcus jannaschii, overexpressed, purified and characterized. The gene product from M. jannaschii shows 5' endo-/exonuclease and 5' pseudo-Y-endonuclease activities as observed in the FEN-1 in eukaryotes. In addition, Methanococcus jannaschii FEN-1 functions effectively at high concentrations of salt, unlike eukaryotic FEN-1. We have crystallized Methanococcus jannaschii FEN-1 and analyzed its preliminary character. The crystal belongs to the space group of P2(1) with unit cell dimensions of a = 58.93 A, b = 42.53 A, c = 62.62 A and beta = 92.250. A complete data set has been collected at 2.0 A resolution using a frozen crystal.

Blotting, Western↗

PubMed1999

Selective transendothelial migration of hematopoietic progenitor cells: a role in homing of progenitor cells.

To elucidate the mechanisms by which hematopoietic progenitor cells transmigrate via the bone marrow (BM) endothelial cells, we first established endothelial cell lines from BM and lung, and BM fibroblast cell lines; then we established an in vitro model of transendothelial migration of hematopoietic progenitor cells in the presence of chemoattractants secreted by BM fibroblast cells. The BM endothelial cells expressed vascular cell adhesion molecule-1 (VCAM-1), but the lung endothelial cells did not. The BM fibroblast cells secreted chemoattractants including stroma cell-derived factor (SDF)-1, which could attract hematopoietic progenitor cells to BM and activate the adhesion molecules expressed on hematopoietic progenitor cells after rolling along the endothelial cells. Anti-SDF-1 antibody inhibited the transendothelial migration of a hematopoietic progenitor cell line, FDCP-2. FDCP-2 that expressed very late activation antigen-4 (VLA-4) and normal progenitor cells transmigrated through BM endothelial cells but not lung endothelial cells, even if in the presence of chemoattractants produced by BM fibroblasts. Both anti-VLA-4 and anti-VCAM-1 antibodies inhibited the transendothelial migration of FDCP-2 cells and normal hematopoietic progenitor cells. These findings suggest that the transendothelial migration of hematopoietic progenitor cells is characteristic of BM endothelial cells, and that VLA-4/VCAM-1 and SDF-1 play important roles in the transendothelial migration and, consequently, homing of hematopoietic progenitor cells to BM.

Animals↗

PubMed1999

In vitro and in vivo studies of 1H NMR visibility to detect deoxyhemoglobin and deoxymyoglobin signals in myocardium.

1H nuclear magnetic resonance (NMR) spectroscopy can be used noninvasively to detect the proximal histidyl N delta proton signals of deoxymyoglobin in the myocardium. However, the quantification of deoxymyoglobin is based on the assumption that the deoxymyoglobin signal detected is not contaminated by the deoxyhemoglobin signals contributed from the blood. The purpose of this study was to conduct in vitro and in vivo 1H NMR studies to examine the in vivo NMR visibility of deoxyhemoglobin in the myocardium. The results demonstrate that the NMR visibility of alpha and beta subunits of deoxyhemoglobin is sensitive to the pulse width for spin excitation because of short T2 relaxation times, and they are not NMR visible in the canine myocardium in vivo at 4.7 T when a 0.5-1.0 msec long Gaussian excitation pulse is used. Therefore, the resonance peak detected at approximately 72 ppm (relative to the water resonance) in the ischemic canine myocardium in vivo is dominated by deoxymyoglobin.

Animals↗

PubMed1999

The surgical treatment of fixed subaortic stenosis: a clinical experience in Japan.

We report herein the results of a retrospective study conducted on ten consecutive Japanese patients who underwent successful surgical relief of fixed subaortic stenosis between 1972 and 1994 at ages ranging from 8 months to 21 years, and followed for 3.6 years and 26 years. Associated cardiovascular defects were present in six patients, two had a history of infective endocarditis, a discrete fibrous ring was found in nine patients, and a redundant abnormal sheet was found in one. A stenotic structure was removed in nine patients and incised in one, while myotomy was additionally performed in one. There were no early complications or deaths. Cardiac catheterization revealed a significant decrease in the peak systolic pressure gradient from 84+/-22 mm Hg preoperatively to 32+/-22 mm Hg postoperatively (P = 0.0017). Reoperation of an aortic valve replacement with or without valvular annulus enlargement was required in four patients because of a small annulus with aortic insufficiency or infective endocarditis. Infective endocarditis was a major cause of late mortality (n = 1) and morbidity (n = 1), but the remaining eight patients have been asymptomatic. Thus, although this lesion is relatively rare in Japan, the typical discrete type may be more common than previously believed. While a relief operation is associated with low early mortality, the palliative aspect regarding pathology of the aortic valve should not be underestimated, including poor growth of the valve annulus, deterioration of aortic insufficiency, and infective endocarditis. The most appropriate operative procedure for reoperation remains to be evolved.

Adolescent↗

PubMed1999

Mitral valve replacement in patients younger than 6 years of age.

UNLABELLED: We present our experience in mitral valve replacement (including left-sided tricuspid valve in corrected transposition) in patients younger than 6 years of age. The long term results were examined with special focus on re-replacement of the valve. Between 1974 and 1995, we performed mitral valve replacement in 14 patients younger than 6 years of age, with no operative mortality. There were 3 late deaths, caused by endocarditis, valve thrombosis, and congestive heart failure, respectively. The five-year-survival rate after primary replacement was 85%, and the ten-year-survival rate was 75%, using Kaplan-Meier analysis. Ten patients (11 occasions) required repeated mitral valve replacements at 2 months to 17 years after the original replacement. The indication for the second or third mitral valve replacement was paravalvular leakage (2 patients), valve thrombosis (1 patient), degeneration in the porcine prosthesis (3 patients), and patient outgrowth of the original small prosthesis (5 patients). Again there was no operative mortality. One patient who suffered from multiple occasions of valve thrombosis died at two years after the second replacement. All patients who had outgrown the prosthetic valve received larger prosthesis at the second replacement than at the primary replacement. The actuarial percentage of freedom from valve-related events at 3 years, 5 years, and at 10 years, was 50%, 37%, and 8%, respectively. CONCLUSIONS: Mitral valve replacement in patients younger than 6 years of age can be performed relatively safely, but meticulous follow-up and appropriate decision making for re-replacement is mandatory for the long-term survival of these patients.

Child↗

PubMed1999

Structure-based identification of a novel NTPase from Methanococcus jannaschii.

Almost half of the entire set of predicted genomic products from Methanococcus jannaschii are classified as functionally unknown hypothetical proteins. We present a structure-based identification of the biochemical function of a protein with an as yet unknown function from a M. jannaschii gene, Mj0226. The crystal structure of Mj0226 protein determined at 2.2 A resolution reveals that the protein is a homodimer and each monomer folds into an elongated alpha/beta structure of a new fold family. Comparisons of Mj0226 protein with protein structures in the database, however, indicate that one part of the protein is homologous to some of the nucleotide-binding proteins. Biochemical analysis shows that Mj0226 protein is a novel nucleotide triphosphatase that can efficiently hydrolyze nonstandard nucleotides such as XTP to XMP or ITP to IMP, but not the standard nucleotides, in the presence of Mg2+ or Mn2+ ions.

Acid Anhydride Hydrolases↗

PubMed1999

Structure and mechanism of glutamate racemase from Aquifex pyrophilus.

Glutamate racemase (MurI) is responsible for the synthesis of D-glutamate, an essential building block of the peptidoglycan layer in bacterial cell walls. The crystal structure of glutamate racemase from Aquifex pyrophilus, determined at 2.3 A resolution, reveals that the enzyme forms a dimer and each monomer consists of two alpha/beta fold domains, a unique structure that has not been observed in other racemases or members of an enolase superfamily. A substrate analog, D-glutamine, binds to the deep pocket formed by conserved residues from two monomers. The structural and mutational analyses allow us to propose a mechanism of metal cofactor-independent glutamate racemase in which two cysteine residues are involved in catalysis.

Amino Acid Isomerases↗

PubMed1999

Neurological complications after stem cell transplantation in childhood.

We analyzed the incidence of neurological complications in 77 patients receiving stem cell transplantation (SCT), and 12 patients (15.8%) had the following symptoms: convulsions, intracranial hemorrhage, and leukoencephalopathy. Although statistically not significant, neurological complications were seen more frequently in patients after allogeneic transplantation, and in those with acute graft-versus-host disease (GVHD) exceeding grade II. The most significant risk factor for neurological complications was identified as unrelated donor allogenic transplantation (P = 0.016). Complications were categorized into three groups, based on time of onset and symptoms: (1) convulsions during the conditioning period, (2) intracranial hemorrhage during the period of granulocyte recovery, and (3) leukoencephalopathy at around 2 months after SCT. We propose awareness of the risks of neurological complications in each period after SCT so that immediate and effective treatment of patients can be instigated.

Adolescent↗

PubMed1999

Multiple acquisitions via horizontal transfer of a group I intron in the mitochondrial cox1 gene during evolution of the Araceae family.

A group I intron has recently been shown to have invaded mitochondrial cox1 genes by horizontal transfer many times during the broad course of angiosperm evolution. To investigate the frequency of acquisition of this intron within a more closely related group of plants, we determined its distribution and inferred its evolutionary history among 14 genera of the monocot family Araceae. Southern blot hybridizations showed that 6 of the 14 genera contain this intron in their cox1 genes. Nucleotide sequencing showed that these six introns are highly similar in sequence (97.7%-99.4% identity) and identical in length (966 nt). Phylogenetic evidence from parsimony reconstructions of intron distribution and phylogenetic analyses of intron sequences is consistent with a largely vertical history of intron transmission in the family; the simplest scenarios posit but one intron gain and two losses. Despite this, however, striking differences in lengths of exonic co-conversion tracts, coupled with the absence of co-conversion in intron-lacking taxa, indicate that the six intron-containing Araceae probably acquired their introns by at least three and quite possibly five separate horizontal transfers. The highly similar nature of these independently acquired introns implies a closely related set of donor organisms.

Base Sequence↗

PubMed1999

An hrcU-homologous gene mutant of Xanthomonas campestris pv. glycines 8ra that lost pathogenicity on the host plant but was able to elicit the hypersensitive response on nonhosts.

Transposon mutagenesis was used to isolate nonpathogenic mutants of Xanthomonas campestris pv. glycines 8ra, which causes bacterial pustule disease in soybean. A 6.1-kb DNA region in which a mutation gave loss of pathogenicity was isolated and found to carry six open reading frames (ORFs). Four ORFs had homology with hrcU, hrcV, hrcR, and hrcS genes of Ralstonia solanacearum and X. campestris pv. vesicatoria. One nonpathogenic mutant, X. campestris pv. glycines H80, lost pathogenicity on soybean but was able to elicit the hypersensitive response (HR) on nonhost pepper and tomato plants. This mutant still multiplied as well as the wild type in the leaves or cotyledons of soybean. Although the DNA and amino acid sequences showed high homology with known hrp genes, the hrcU-homolog ORF is not required for HR induction on nonhost plants, pepper and tomato, or for the multiplication of bacteria in the host plant. This gene was only required for the pathogenic symptoms of X. campestris pv. glycines 8ra on soybean.

Amino Acid Sequence↗

PubMed1999

Crystallization and preliminary x-ray analysis of glutamate racemase from Aquifex pyrophilus, a hyperthermophilic bacterium.

Glutamate racemase catalyzes the reversible reaction of L-glutamate to D-glutamate, an essential component of the bacterial cell wall. Glutamate racemase from Aquifex pyrophilus has been crystallized by the hanging-drop vapor-diffusion method using polyethylene glycol 6000 as a precipitant. The crystals belong to space group P6122 or P6522 with unit-cell parameters a = b = 72.1, c = 185.02 A. The asymmetric unit contains one molecule, corresponding to a Vm value of 2.35 A3 Da-1. Complete data sets from a native and a mercury-derivative crystal have been collected at 2.0 and 2.3 A resolution, respectively, using a synchrotron-radiation source.

Amino Acid Isomerases↗

PubMed1999

[Roles of p53 in adriamycin-induced cell death and in acquisition of adriamycin resistance in adult T-cell leukemia (ATL) cells].

In order to define the roles of p53 in acquisition of drug resistance in ATL cell lines, we prepared several ATL cell lines which differed in sensitivity to adriamycin (ADM), and examined their functional p53 statuses, expressions of p53, p21, Bcl-2, Bax, and cell cycles. Our findings demonstrated: (1) Regardless of sensitivity to ADM, most of the cell lines, including ADM-resistant cell lines, carried wild-type p53. (2) Only one cell line, ED-S, which was the most sensitive to ADM carried non-functional mutated-type p53. (3) In the ATL cells carrying wild-type p53, regardless of sensitivity to ADM, ADM-treatment led to an elevation of p53 protein level with concomitant elevations of p21 and Bax protein levels. (4) In the cell line expressing mutated-type p53, ADM-treatment at the concentration of IC50 induced elevations of p53, and Bax protein levels but did not p21 protein level. (5) Expression of Bcl-2 protein did not change in any of the cell lines by treatment with ADM at their respective IC50 levels, but increased in the ADM-resistant cell line when it was treated with ADM at IC50 of its parent cell line. (6) In the cell cycle analysis, ADM-treatment induced G1- and G2-arrest and then apoptosis in the cell lines with wild-type p53, whereas it induced only G2-arrest and then apoptosis in the cell line with mutated-type p53 at the same time course as in those with wild-type p53. These findings suggest that p53 does not play a leading part either in the apoptosis induced by ADM, or in the acquisition of resistance to ADM in ATL cells, and that ADM-induced apoptosis is mediated by multiple pathways leading to the activation of effector molecules.

Antineoplastic Agents↗

PubMed1999

[Emergency coronary artery bypass grafting for acute coronary syndrome].

Between 1987 and 1998, 22 patients underwent emergency coronary artery bypass grafting for the treatment of acute coronary syndrome. Overall hospital mortality was 22.7% (5/22) versus 1.8% (9/501) in patients operated on electively (p < 0.01). There were no hospital deaths in the unstable angina group. Three patients (37.5%) in the myocardial infarction group and two patients (40%) in the failed catheter intervention group died due to postoperative low cardiac output syndrome (LOS) or mediastinitis. As a complication of mechanical supports, lower extremity ischemia was a risk factor for mortality. Postoperatively six patients (27.3%) had LOS. Univariate analyses showed that age greater than 70 years, old myocardial infarction, poor ejection fraction, preoperative shock, and left main trunk or three vessel disease were significantly associated with increased LOS. To improve the surgical results, it is considered that improvement of intraoperative myocardial protection, effective combination with catheter interventional therapy and careful use of mechanical supports are needed for these compromised patients.

Adult↗

PubMed1999

[Adverse effects of anti-thymocyte globulin/anti-lymphocyte globulin therapy].

This single-centre study evaluated the adverse effects of anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG) as used for the treatment of aplastic anemia and/or for conditioning regimens prior to stem cell transplantation. ATG/ALG was given to 29 patients a total of 37 times. The incidence of adverse effects was 62.1% (23/37), and fever was the most frequent adverse effect. Therapy was discontinued in only 4 patients (10.8%) due to severe adverse effects. Adverse effects occurred more frequently with ATG (rabbit-derived) than with ALG (horse-derived). Seven patients underwent 2 or 3 cycles of ATG/ALG therapy, for a combined total of 8 times; 6 of those patients (75% (6/8)) experienced adverse effects. Shorter intervals between repeated cycles of therapy appeared to heighten the risk of adverse reactions.

Adolescent↗

PubMed1998

A new low density lipoprotein receptor related protein, LRP5, is expressed in hepatocytes and adrenal cortex, and recognizes apolipoprotein E.

The isolation and characterization of rabbit and human cDNAs revealed a new low density lipoprotein receptor (LDLR)-related protein (LRP) designated as LRP5. Human LRP5 cDNA encodes a 1, 616-amino acid type I membrane-like protein with three ligand binding repeats in its extracellular region. LDLR-deficient cells transduced by recombinant adenovirus containing human LRP5 exhibited increased binding of apolipoprotein E (apoE)-enriched beta-migrating very low density lipoprotein. Northern blotting and in situ hybridization revealed a high level of LRP5 expression in hepatocytes and the adrenal gland cortex. In LDLR-deficient Watanabe heritable hyperlipidemic rabbits, LRP5 mRNA was increased in the liver and accumulated in cholesterol-laden foam cells of atherosclerotic lesions.

Adrenal Cortex↗