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Biomedical subjects

Y S Han

Publications and source records attributed to Y S Han.

At least 19 recordsLinked to original sources

Outcome of patients with recurrent hepatocellular carcinoma in liver transplantation.

Liver transplantation (OLT) is the treatment of choice for patients with hepatic cirrhosis related hepatocellular carcinoma (HCC). Among 156 liver transplant patients for HCC from June 1996 to February 2005, 23 had recurrent HCC. To evaluate risk factors that affect early recurrence of HCC after OLT, we divided the 23 patients into two groups: early (< or =12 months) and late (>12 months) recurrences. Among them, 15 patients were dead and eight alive patients had been followed to 31 July 2005. The most common recurrence site was the grafted liver (n = 15), next was bone (n = 11), lung (n = 8), lymph node (n = 6), brain (n = 4), skin (n = 2), adrenal gland (n = 1). There were no significant differences between the two groups in age or tumor size, number of tumors, cell differentiation, alpha-feto protein levels, tumor staging, number of patients within Milan criteria, steroid pulse therapy, infectious diseases, and immunostaining of tumor. In our study, there were no risk factors that predict early tumor recurrence. We noticed that more patients in the early recurrence group were excluded by Milan criteria due to a more progressed tumor staging with higher mean levels of serum alpha-feto protein.

Adult↗

Prognosis after liver transplantation predicted by preoperative MELD score.

The model for end-stage liver disease (MELD) has been an excellent predictor of 3-month mortality among cirrhotic patients awaiting orthotopic liver transplantation (OLT). The aim of this study was to evaluate whether the preoperative MELD score predicts short-term prognosis after OLT. We enrolled 98 adult liver transplant patients performed at our center from January 2001 to December 2002. In univariate analysis of risk factors for death within 3 and 6 months after liver transplantation, serum total bilirubin, creatinine, MELD score, hyponatremia with ascites, Child-Turcotte-Pugh (CTP) score were statistically significant parameters (P < .05). By logistic regression, none of the risk factors were subjected to multivariate analysis showed statistical significance. The odds ratios of the MELD score, hyponatremia with ascites, CTP score within 3 months were 0.997, 1.151, and 0.726 with 95% confidence intervals of [0.899, 1.105], [0.102, 12.959], and [0.389, 1.352], respectively. The odds ratio of MELD score, hyponatremia with ascites, CTP score within 6 months were 0.996, 0.914, and 0.764, with 95% confidence intervals of [0.901, 1.102], [0.089, 9.369], and [0.417, 1.401], respectively. Although MELD score has been a good predictor of short-term prognosis before OLT, MELD did not show an influence on the short-term prognosis after liver transplantation in this study.

Analysis of Variance↗

Outcomes of hepatitis B virus recurrence after liver transplantation.

The introduction of high doses of hepatitis B immune globulin (HBIG) and lamivudine for liver transplantation (OLT) prophylaxis has reduced the risk of hepatitis B recurrence and improved the survival of patients transplanted for hepatitis B virus (HBV)-related liver disease. But, posttransplant prophylaxis strategies to treat the recurrence of HBV have not yet been standardized. We analyzed 23 patients with HBV recurrence among 340 HBV-associated liver transplants performed from September 1996 to April 2004 (6.7%). Nine patients underwent deceased donor OLT and 14, living donor OLT. Mean follow-up was 37 months. Seroconversion after recurrence was observed in 6 of 23 patients (26%). Mean time to HBV recurrence tended to be shorter among the seroconversion (+) patients compared to seroconversion (-) patients (10 months vs 19.7 months; P = .062). Seroconversion rate after HBIG and lamivudine combination therapy for patients with HBV recurrence was 37.5% and time to seroconversion after HBV recurrence was 1.7 months. Seroconversion was best achieved when the pretransplant HBV DNA level was high and HBeAg was positive. Also, seroconversion rate was increased when HBV DNA level was low and the alanine transferase level high at the time of recurrence and when the time to recurrence after transplantation was short. Seroconversion after HBV recurrence, which was observed in 26%, may be increased in selected cases. Accordingly, aggressive treatment should be undertaken after HBV recurrence.

Antiviral Agents↗

Liver transplantation for hepatocellular carcinoma with bile duct thrombi.

In a few cases of hepatocellular carcinoma (HCC), jaundice results from obstructive causes, including tumor invasion or thrombi in the bile duct. We have reported herein our experience with liver transplantation (OLT) for HCC cares showing bile duct thrombi (BDT). From September 1996 to August 2004, 140 adult patients underwent OLT for HCC at our center. Four patients (2.9%) who had OLT performed for HCC had BDT and were included in this study. The patients were all men of mean age 57.0 years. The initial total bilirubin levels were in the range of 2.0 to 30.5 mg/dL. The sizes of the tumors ranged from 2.0 cm to 3.0 cm in diameter, all were single lesions. The median follow-up period was 20.6 months (range: 17.6 to 28.1 months). The only case in which the BDT was identified intraoperatively died 20 months after OLT due to multiple intrahepatic recurrences. The other three patients were alive, showing no evidence of recurrence at the end of follow-up. Although a series of four is too small to reach any conclusion, we suggest that OLT may be a treatment option for HCC with BDT in selected cases.

Adult↗

Safety of donors with fatty liver in liver transplantation.

Steatotic liver graft transplantation affect donor safety as well as recipient survival. We investigated safety of donors according to the extent of fatty change. We retrospectively reviewed donors who underwent right hepatectomy from September 1999 to April 2005, dividing them into three groups according to degree of macrovesicular fatty change upon intraoperative liver biopsy. Group 1 included patients with macrovesicular steatosis of 0 approximately 9%: group 2, 10 approximately 19% and group 3, at least 20%. Two hundred forty-five donors were enrolled with a male to female ratio of 2.02:1 and mean age of 31.8 years. There were 163 donors in group 1, 75 in group 2, and seven in group 3. There was no statistically significant difference in body mass index, operative time, blood loss, postoperative peak serum bilirubin, and aspartate transaminase levels among groups 1, 2, and 3. Overall complication rate, including reoperation, biliary stricture, wound infection, ileus, transfusion, bile leak and fluid collection were not different between the groups. Postoperative hospital stay was also not different. Peak alanine transaminase level was different between each group, and prothrombin time between group 1 and 3, but days until return to normal levels in all measured laboratory parameters were not different. Residual liver volume percent was significantly smaller among group 1 compared to others. In conclusion, fatty livers with less than 30% macrovesicular steatosis may be good donor candidates without significant complications as long as sufficient residual liver volume is left for the donor.

Adolescent↗

Self-reported prevalence and risk factors of asthma among Korean adolescents: 5-year follow-up study, 1995-2000.

OBJECTIVES: The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires have shown that the prevalence of childhood asthma is increasing worldwide. Although Asian countries used to have lower prevalence rates of allergic disease than Western countries, this prevalence is increasing in several Asian countries. To determine whether the prevalence of childhood asthma is changing in Korean adolescents, we compared findings from nationwide cross-sectional surveys in 1995 and 2000 on populations of middle-school children using the Korean version of the ISAAC questionnaire. METHODS: We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 15,481 children, ages 12-15, and encompassing all three grades in middle school, selected from 34 schools across the nation; the response rate was 97.3%. In 2000, 15,894 children were selected from 31 of the same schools, and the response rate was 96.4%. The SAS system version 8.0 was utilized for all statistical analyses. RESULTS: The WQ showed that the lifetime and 12-month prevalence of wheeze did not change from 1995 to 2000. While the 12-month prevalence rates of sleep disturbed by wheezing and night cough increased, the rates of severe attack of wheezing and exercise-induced wheeze did not change, over this period of time. The lifetime prevalence of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3% in 2000, as did the 12-month prevalence of asthma treatment, from 1.0% in 1995 to 1.9% in 2000. The AVQ also showed increases in the lifetime and 12-month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time. These were especially because of significant increases in the Provincial cities of Korea. Interestingly, the 12-month prevalence of wheeze was consistently high in Cheju with low air pollution indices, whereas this rate was low in Ulsan and Ansan with very high air pollution indices. Risk factor analysis showed that body mass index (BMI), passive smoking, and living with a dog or cat, but not air pollution, were associated with higher risk of wheeze. CONCLUSIONS: In the 5-year period from 1995 to 2000, the prevalence of asthma symptoms has increased in Korean adolescents, much of it because of increases in Provincial Centers. BMI, passive smoking, and living with a dog or cat are important risk factors. Environmental factors other than air pollution may be associated with increases in asthma, especially in Provincial Centers.

Adolescent↗

Mutational effects on thermostable superoxide dismutase from Aquifex pyrophilus: understanding the molecular basis of protein thermostability.

We designed two mutants of superoxide dismutase (SOD), one is thermostable and the other is thermolabile, which provide valuable insight to identify amino acid residues essential for the thermostability of the SOD from Aquifex pyrophilus (ApSOD). The mutant K12A, in which Lys12 was replaced by Ala, had increased thermostability compared to that of the wild type. The T(1/2) value of K12A was 210 min and that of the wild type was 175 min at 95 degrees C. However, the thermostability of the mutant E41A, which has a T(1/2) value of 25 min at 95 degrees C, was significantly decreased compared to the wild type of ApSOD. To explain the enhanced thermostability of K12A and thermolabile E41A on the structural basis, the crystal structures of the two SOD mutants have been determined. The results have clearly shown the general significance of hydrogen bonds and ion-pair network in the thermostability of proteins.

Bacterial Proteins↗

Biochemical characterization of a novel hypoxanthine/xanthine dNTP pyrophosphatase from Methanococcus jannaschii.

A novel dNTP pyrophosphatase, Mj0226 from Methanococcus jannaschii, which catalyzes the hydrolysis of nucleoside triphosphates to the monophosphate and PPi, has been characterized. Mj0226 protein catalyzes hydrolysis of two major substrates, dITP and XTP, suggesting that the 6-keto group of hypoxanthine and xanthine is critical for interaction with the protein. Under optimal reaction conditions the k(ca)(t) /K(m) value for these substrates was approximately 10 000 times that with dATP. Neither endonuclease nor 3'-exonuclease activities were detected in this protein. Interestingly, dITP was efficiently inserted opposite a dC residue in a DNA template and four dNTPs were also incorporated opposite a hypoxanthine residue in template DNA by DNA polymerase I. Two protein homologs of Mj0226 from Escherichia coli and Archaeoglobus fulgidus were also cloned and purified. These have catalytic activities similar to Mj0226 protein under optimal conditions. The implications of these results have significance in understanding how homologous proteins, including Mj0226, act biologically in many organisms. It seems likely that Mj0226 and its homologs have a major role in preventing mutations caused by incorporation of dITP and XTP formed spontaneously in the nucleotide pool into DNA. This report is the first identification and functional characterization of an enzyme hydrolyzing non-canonical nucleotides, dITP and XTP.

Archaeoglobus↗

Repair activities of 8-oxoguanine DNA glycosylase from Archaeoglobus fulgidus, a hyperthermophilic archaeon.

Oxidative DNA damage is caused by reactive oxygen species formed in cells as by products of aerobic metabolism or of oxidative stress. The 8-oxoguanine (8-oxoG) DNA glycosylase from Archaeoglobus fulgidus (Afogg), which excises an oxidatively-damaged form of guanine, was overproduced in Escherichia coli, purified and characterized. A. fulgidus is a sulfate-reducing archaeon, which grows at between 60 and 95 degrees C, with an optimum growth at 83 degrees C. The Afogg enzyme has both DNA glycosylase and apurinic/apyrimidinic (AP) lyase activities, with the latter proceeding through a Schiff base intermediate. As expected for a protein from a hyperthermophilic organism, the enzyme activity is optimal near pH 8.5 and 60 degrees C, denaturing at 80 degrees C, and is thermally stable at high levels of salt (500mM). The Afogg protein efficiently cleaves oligomers containing 8-oxoG:C and 8-oxoG:G base pairs, and is less effective on oligomers containing 8-oxoG:T and 8-oxoG:A mispairs. While the catalytic action mechanism of Afogg protein is likely similar to the human Ogg1 (hOgg1), the DNA recognition mechanism and the basis for 8-oxoG substrate specificity of Afogg differ from that of hOgg.

Amino Acid Sequence↗

Mutational analyses of Aquifex pyrophilus DNA ligase define essential domains for self-adenylation and DNA binding activity.

We constructed nine deletion mutants of NAD+-dependent DNA ligase from Aquifex pyrophilus to characterize the functional domains. All of DNA ligase deletion mutants were analyzed in biochemical assays for NAD+-dependent self-adenylation, DNA binding, and nick-closing activity. Although the mutant lsub1 (91-362) included the active site lysine (KxDG), self-adenylation was not shown. However, the mutants lsub6 (1-362), lsub7 (1-516), and lsub9 (1-635) showed the same adenylation activity as that of wild type. The lsub5 (91-719), which has the C-terminal domain (487-719) as to lsub4 (91-486), showed minimal adenylation activity. These results suggest that the presence of N-terminal 90 residues is essential for the formation of an enzyme-AMP complex, while C-terminal domain (487-719) appears to play a minimal role in adenylation. It was found that the presence of C-terminal domain (487-719) is indispensable for DNA binding activity of lsub5 (91-719). The mutant lsub9 (1-635) showed reduced DNA binding activity compared to that of wild type, suggesting the contribution of the domain (636-719) for the DNA binding activity. Thus, we concluded that the N-terminal 90 residues and C-terminal domain (487-719) of NAD+-dependent DNA ligase from A. pyrophilus are mutually indispensable for binding of DNA substrate.

Adenosine Monophosphate↗

XAFS study of copper species stabilized in the interlayer space of layered perovskite oxides.

New intercalation compounds with Cu2+ ions in the interlayer of layered perovskite oxides, OA(1-x)Ca(2-x)La(x)Nb3O10) (OA = n-octylammonium ion, 0 < or = x < 1), have been prepared by ion-exchange reaction, and characterized by means of XRD and XAS. For the detail elucidation of the fine structure of the Cu K-edge XANES spectra, polarized XAS was applied for the [Cu(en)2]2+ and Cu2+ ions intercalated to the single crystal. According to the XANES and EXAFS spectra measured at Cu K-edge, copper ions are four coordinated. In addition, XANES spectra have shown that the charge transfer from host layer to intercalated ions influences on the chemical state of copper ion.

Journal Article↗

Ion exchange and fixation of rare-earth cation into expandable tetrasilicic fluorine mica.

Rare-earth cation (Nd3+) are incorporated into the interlayer spaces between the silicate layers of synthetic fluorine mica, Na0.665Mg2.68(Si3.98)Al0.02F1.98, by conventional ion exchange reaction. Subsequent migration of the interlayer cations upon calcination into the vacant octahedra of 2:1 layers is followed by powder X-ray diffraction, diffuse-reflectance UV spectroscopy, and X-ray absorption spectroscopy as a function of calcination temperature. It is found from the spectroscopic analyses that the interlayer cations start to migrate into the octahedral vacant sites from 400 degrees C through the hexagonal siloxane ring of the tetrahedral silicate layers. According to the Nd L(III)-edge XANES spectra, the normalized absorption intensity gradually decreases while the FWHM increases with temperature, suggesting that the bonding character of rare-earth cations and silicate lattices evolves from ionic to covalent as the calcination temperature increases.

Journal Article↗

Local structure analysis of Ti species stabilized in ion exchangeable layer solids by x-ray absorption spectroscopy.

Nano-sized titanium dioxides are incorporated into the interlayer spaces of ion-exchangeable layered perovskites, H(1-x)Ca2(x)La(x)Nb3O10 (x=0.0-0.75), by replacing the interlayer protons with positively charged TiO2 nano-sol particles or basic titanium glycolate complex (titanatrane). Powder X-ray diffraction analysis. UV-Vis absorption spectroscopy, thermogravimetric analysis, and N2 adsorption-desorption isotherm measurements show that quantum sized TiO2 particles are stabilized in between perovskite lattices to form micropores (S(BET) = 37-110 m2/g). X-ray absorption spectroscopy at the Ti K-edge was used for investigating the local environment around Ti atoms constituting the interlayer pillars. According to the XANES spectra, the 'as-pillared' Ti species have the same local environments with those of precursory species, which subsequently converted into TiO2 clusters with rutile and anatase-like local structures when TiO2 nano-sol particles and titanatrane are used as pillaring species. respectively. It is also found that the local environment of TiO2 remains almost constant irrespective of the layer charge density, while the TiO2 pillar content and the microporosity increase with the latter.

Journal Article↗

Molecular cloning and characterization of thermostable DNA ligase from Aquifex pyrophilus, a hyperthermophilic bacterium.

A DNA ligase gene from the hyperthermophilic bacterium Aquifex pyrophilus (Ap) was cloned and sequenced. An open reading frame of 2,157 bp that codes for a 82-kDa protein showed 40%-60% homology with a series of NAD+-dependent DNA ligases from different organisms. The recombinant enzyme Ap DNA ligase expressed in Escherichia coli was purified to homogeneity and characterized. The activity of Ap DNA ligase gradually increased in proportion to the concentration of monovalent salt up to 200 mM NaCl, 150 mM KCl, 200 mM NH4Cl, and 350 mM potassium glutamate. The optimum temperature and pH of Ap DNA ligase were greater than 65 degrees C and 8.0-8.6, respectively, for nick-closing activity. More than 75% of the ligation activity was retained after incubation at 95 degrees C for 60 min, whereas the half-lives of Thermus aquaticus and Escherichia coli DNA ligases at 95 degrees C were < or =15 min and 5 min, respectively. Thermostable Ap DNA ligase was applied to repeat expansion detection (RED) and could be a useful enzyme in DNA diagnostics.

Amino Acid Sequence↗

Mast cell chymase expression and mast cell phenotypes in human rejected kidneys.

BACKGROUND: Mast cells (MCs) are known to participate in various types of chronic disease, but their role in chronic renal rejection is poorly understood. Recently, distinct phenotypes of MCs have been described in humans by the demonstration of one protease, chymase. Hence, we questioned whether chymase in MCs could play a role in the pathogenesis of renal rejection in humans. METHODS: We investigated MC chymase expression and MC phenotypes, using immunohistochemical single- and double-staining techniques, in nephrectomy (N = 13) and biopsy (N = 8) specimens of human rejected kidneys. Tissue chymase levels were determined by enzymatic assay for chymase activity. We also examined the association between MC chymase expression and the degree of interstitial fibrosis in these renal allografts. RESULTS: Based on chymase positivity, rejected kidneys were divided into two groups, a chymase-negative [Chy(-)] group and a chymase-positive [Chy(+)] group. Quantitative analysis showed that the number of chymase-positive MCs and tissue chymase levels were significantly higher in the Chy(+) group than in the Chy(-) group. Furthermore, the interstitial fibrotic area in the Chy(+) group was significantly larger than that in the Chy(-) group. Immunodouble staining analysis also demonstrated that a new MC phenotype, positive for chymase but negative for tryptase, was present in the human rejected kidney. CONCLUSIONS: These results show that increased expression of chymase in MCs is related to the severity of interstitial fibrosis in human rejected kidneys.

Adolescent↗

The incidence and clinical characteristics of symptomatic propylthiouracil-induced hepatic injury in patients with hyperthyroidism: a single-center retrospective study.

OBJECTIVES: Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course. METHODS: Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes. RESULTS: Four hundred ninety-seven patients (age 42.6 +/- 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 +/- 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 +/- 288 micromol/L, 143 +/- 111 U/L, and 265 +/- 81 U/L; normal, < 117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 +/- 46.4) days after the PTU withdrawal. CONCLUSIONS: Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.

Adult↗

Reserve capacity for ATP consumption during isometric contraction in human skeletal muscle fibers.

Maximum velocity of the actomyosin ATPase reaction (V(max) ATPase) and ATP consumption rate during maximum isometric activation (ATP(iso)) were determined in human vastus lateralis (VL) muscle fibers expressing different myosin heavy chain (MHC) isoforms. We hypothesized that the reserve capacity for ATP consumption [1 -- (ratio of ATP(iso) to V(max) ATPase)] varies across VL muscle fibers expressing different MHC isoforms. Biopsies were obtained from 12 subjects (10 men and 2 women; age 21--66 yr). A quantitative histochemical procedure was used to measure V(max) ATPase. In permeabilized fibers, ATP(iso) was measured using an NADH-linked fluorometric procedure. The reserve capacity for ATP consumption was lower for fibers coexpressing MHC(2X) and MHC(2A) compared with fibers singularly expressing MHC(2A) and MHC(slow) (39 vs. 52 and 56%, respectively). Tension cost (ratio of ATP(iso) to generated force) also varied with fiber type, being highest in fibers coexpressing MHC(2X) and MHC(2A). We conclude that fiber-type differences in the reserve capacity for ATP consumption and tension cost reflect functional differences such as susceptibility to fatigue.

Adenosine Triphosphatases↗

Temporal aspects of excitation-contraction coupling in airway smooth muscle.

In airway smooth muscle (ASM), ACh induces propagating intracellular Ca2+ concentration ([Ca2+]i) oscillations (5-30 Hz). We hypothesized that, in ASM, coupling of elevations and reductions in [Ca2+]i to force generation and relaxation (excitation-contraction coupling) is slower than ACh-induced [Ca2+]i oscillations, leading to stable force generation. When we used real-time confocal imaging, the delay between elevated [Ca2+]i and contraction in intact porcine ASM cells was found to be approximately 450 ms. In beta-escin-permeabilized ASM strips, photolytic release of caged Ca2+ resulted in force generation after approximately 800 ms. When calmodulin (CaM) was added, this delay was shortened to approximately 500 ms. In the presence of exogenous CaM and 100 microM Ca2+, photolytic release of caged ATP led to force generation after approximately 80 ms. These results indicated significant delays due to CaM mobilization and Ca2+-CaM activation of myosin light chain kinase but much shorter delays introduced by myosin light chain kinase-induced phosphorylation of the regulatory myosin light chain MLC20 and cross-bridge recruitment. This was confirmed by prior thiophosphorylation of MLC20, in which force generation occurred approximately 50 ms after photolytic release of caged ATP, approximating the delay introduced by cross-bridge recruitment alone. The time required to reach maximum steady-state force was >15 s. Rapid chelation of [Ca2+]i after photolytic release of caged diazo-2 resulted in relaxation after a delay of approximately 1.2 s and 50% reduction in force after approximately 57 s. We conclude that in ASM cells agonist-induced [Ca2+]i oscillations are temporally and spatially integrated during excitation-contraction coupling, resulting in stable force production.

Acetylcholine↗