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1.  Quantitation of nanoparticle accumulation in flow using optimized microfluidic chambers 
Journal of drug targeting  2013;22(1):48-56.
The vascular cell adhesion molecule-1 (VCAM-1) targeting peptide sequence, VHPKQHR, is a promising moiety for targeting atherosclerosis through incorporation into nanoparticles such as dendrimers and liposomes.
We aim to develop VCAM-1-targeted nanoparticles that effectively accumulate on the endothelium under shear conditions and to develop robust microfluidic chambers able to house sufficient cells for flow cytometric measurements.
Carboxyfluorescein-labeled monomeric VHP-peptide, tetrameric VHP-dendrimers (bisbidentate or radial architecture, with or without N-terminal acetylation) and VHP-peptide liposomes were prepared. Human umbilical vein endothelial cells were treated with nano-particles under 0 or 2.9 dyne/cm2 shear, and particle binding was quantified. Flow chambers cured at various temperatures, with or without glass backings were fabricated, characterized for deformation and applied in experiments.
Although liposomes accumulated with highest efficiency, dendrimers also demonstrated specific binding. N-terminal acetylation significantly reduced dendrimer binding, and despite shorter movement range, bisbidentate dendrimers outperformed radial dendrimers, suggesting multiple epitope presence within its estimated arm-span of 57 Å. Under shear, while liposome binding increased 300%, dendrimer binding to cells decreased 65%. Through higher temperature curing and glass backing insertion, polydimethylsiloxane flow chambers maintaining rectangular cross-section with aspect-ratio as low as 1:111 were achieved.
Optimized dendrimers and liposomal nanocarriers specifically accumulated onto cells within microfluidic chambers.
PMCID: PMC4004627  PMID: 24079404
Atherosclerosis; dendrimers; in vitro model; liposomes; peptide; targeted drug delivery
2.  Production of Endoglucanase, Beta-glucosidase and Xylanase by Bacillus licheniformis Grown on Minimal Nutrient Medium Containing Agriculture Residues 
Bacillus licheniformis was grown in minimal nutrient medium containing 1% (w/v) of distillers dried grain with soluble (DDGS), palm kernel meal (PKM), wheat bran (WB) or copra meal (CM), and the enzyme activity of endoglucanase, β-glucosidase, xylanase and reducing sugars was measured to investigate a possibility of using cost-effective agricultural residues in producing cellulolytic and hemicellulolytic enzymes. The CM gave the highest endoglucanase activity of 0.68 units/mL among added substrates at 48 h. CM yielded the highest titres of 0.58 units/ml of β-glucosidase, compared to 0.33, 0.23, and 0.16 units/mL by PKM, WB, and DDGS, respectively, at 72 h. Xylanase production was the highest (0.34 units/mL) when CM was added. The supernatant from fermentation of CM had the highest reducing sugars than other additional substrates at all intervals (0.10, 0.12, 0.10, and 0.11 mg/mL respectively). It is concluded that Bacillus licheniformis is capable of producing multiple cellulo- and hemicellololytic enzymes for bioethanol production using cost-effective agricultural residues, especially CM, as a sole nutrient source.
PMCID: PMC4093570  PMID: 25050035
Agricultural Residues; Bacillus licheniformis; β-Glucosidase; Endoglucanase; Xylanase
3.  Stabilization of p21 (Cip1/WAF1) following Tip60-dependent acetylation is required for p21-mediated DNA damage response 
Cell Death and Differentiation  2012;20(4):620-629.
The molecular mechanisms controlling post-translational modifications of p21 have been pursued assiduously in recent years. Here, utilizing mass-spectrometry analysis and site-specific acetyl-p21 antibody, two lysine residues of p21, located at amino-acid sites 161 and 163, were identified as Tip60-mediated acetylation targets for the first time. Detection of adriamycin-induced p21 acetylation, which disappeared after Tip60 depletion with concomitant destabilization of p21 and disruption of G1 arrest, suggested that Tip60-mediated p21 acetylation is necessary for DNA damage-induced cell-cycle regulation. The ability of 2KQ, a mimetic of acetylated p21, to induce cell-cycle arrest and senescence was significantly enhanced in p21 null MEFs compared with those of cells expressing wild-type p21. Together, these observations demonstrate that Tip60-mediated p21 acetylation is a novel and essential regulatory process required for p21-dependent DNA damage-induced cell-cycle arrest.
PMCID: PMC3595487  PMID: 23238566
p21 (Cip1/WAF1); Tip60; acetylation; cell-cycle arrest; DNA damage
4.  CT findings of pulmonary non-tuberculous mycobacterial infection in non-AIDS immunocompromised patients: a case-controlled comparison with immunocompetent patients 
The British Journal of Radiology  2013;86(1024):20120209.
To describe CT findings of non-tuberculous mycobacteria (NTM) pulmonary infection in non-AIDS immunocompromised patients (ICPs) and to compare these findings with those in immunocompetent patients.
From July 2000 to August 2007, 369 patients (mean age 58.3 years; 169 males and 200 females) with pulmonary NTM infection were retrospectively reviewed. Of these 369 patients, 24 ICPs (mean age 64.8 years; 15 males and 9 females) were identified. 16 patients had diabetes mellitus, and 6 patients had received long-term steroid therapy. One had received solid organ transplantation and one had received high-dose chemotherapy for haematological disease. 24 age- and sex-matched immunocompetent patients (mean age 64.6 years; 15 males and 9 females) were selected as the control group from the same registry. CT images were reviewed in consensus by three chest radiologists, who were blinded to immune status. Each lung lobe was evaluated in terms of extent of the lesion, bronchiectasis, parenchymal opacity and the presence of ancillary findings.
A total of 287 lobes were evaluated in ICPs and the control group. The ICPs showed a higher prevalence of ill-defined nodules, with cavities and large opacity >2 cm with/without cavity (p=0.03, 0.04 and 0.02, respectively). Regardless of the immune status, the most common CT findings were bronchiectasis and ill-defined nodules without cavity.
The most common CT findings of pulmonary NTM infection in ICPs were bronchiectasis and ill-defined nodules, similar to those in the control group. Ill-defined nodules with cavity and large opacity >2 cm with/without cavity were more frequently found in ICPs.
Advances in knowledge:
In patients affected by NTM infection, large opacities and cavitation in pulmonary nodules are more frequent in ICPs than in immunocompetent patients.
PMCID: PMC3635784  PMID: 23440166
5.  Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia 
Translational Psychiatry  2013;3(10):e321-.
Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.
PMCID: PMC3818014  PMID: 24169640
hippocampus; immune; inflammation; postmortem brain; RNA-Seq; schizophrenia
6.  Transthoracic fine-needle aspiration biopsy of the lungs using a C-arm cone-beam CT system: diagnostic accuracy and post-procedural complications 
The British Journal of Radiology  2012;85(1014):e217-e222.
The purpose of our study was to evaluate the diagnostic accuracy of transthoracic fine-needle aspiration biopsy (TFNAB) using a C-arm cone-beam CT (CBCT) system and to assess risk factors for immediate post-procedural complications in patients with lung lesions.
From October 2007 to April 2009, 94 TFNAB procedures using a C-arm system were studied in 91 patients with pulmonary lesions a chest CT scans. We retrospectively reviewed the patients' radiological and histopathological findings. We evaluated the lesion size, lesion abutted to pleura and presence or absence of emphysema along the needle path, lesion depth, visibility of target lesion and patient's position. Pneumothorax and pulmonary haemorrhage were assessed after TFNAB. Overall diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analysed.
In 94 TFNAB procedures, 58 lesions were malignant and 36 were benign. The sensitivity, specificity, PPV, NPV and overall diagnostic accuracy rate of TFNAB were 93.1%, 100%, 100%, 90% and 97.9%, respectively. Pneumothorax was developed in 24 procedures. None of the parameters showed significant impact on the frequency of the pneumothorax. Overall haemorrhage occurred in 43 procedures. The incidence of overall haemorrhage was higher in patients with smaller lesions, longer pleural distance and pleural abutted lesions (p<0.05). Differences in visibility at projection radiographs were statistically significant between patients with or without perilesional haemorrhage (p<0.05).
Transthoracic fine-needle aspiration biopsy using a C-arm CBCT system is feasible for imaging guidance of lung lesion and early detection of the procedural-related complications.
PMCID: PMC3474125  PMID: 22010033
8.  Effects of Synchronicity of Carbohydrate and Protein Degradation on Rumen Fermentation Characteristics and Microbial Protein Synthesis 
A series of in vitro studies were carried out to determine i) the effects of enzyme and formaldehyde treatment on the degradation characteristics of carbohydrate and protein sources and on the synchronicity of these processes, and ii) the effects of synchronizing carbohydrate and protein supply on rumen fermentation and microbial protein synthesis (MPS) in in vitro experiments. Untreated corn (C) and enzyme-treated corn (EC) were combined with soy bean meal with (ES) and without (S) enzyme treatment or formaldehyde treatment (FS). Six experimental feeds (CS, CES, CFS, ECS, ECES and ECFS) with different synchrony indices were prepared. Highly synchronous diets had the greatest dry matter (DM) digestibility when untreated corn was used. However, the degree of synchronicity did not influence DM digestibility when EC was mixed with various soybean meals. At time points of 12 h and 24 h of incubation, EC-containing diets showed lower ammonia-N concentrations than those of C-containing diets, irrespective of the degree of synchronicity, indicating that more efficient utilization of ammonia-N for MPS was achieved by ruminal microorganisms when EC was offered as a carbohydrate source. Within C-containing treatments, the purine base concentration increased as the diets were more synchronized. This effect was not observed when EC was offered. There were significant effects on VFA concentration of both C and S treatments and their interactions. Similar to purine concentrations, total VFA production and individual VFA concentration in the groups containing EC as an energy source was higher than those of other groups (CS, CES and CFS). The results of the present study suggested that the availability of energy or the protein source are the most limiting factors for rumen fermentation and MPS, rather than the degree of synchronicity.
PMCID: PMC4093482  PMID: 25049798
Enzyme; Formaldehyde; Synchronicity; Rumen Fermentation; Microbial Protein Synthesis
9.  EIT-Based Fabric Pressure Sensing 
This paper presents EIT-based fabric sensors that aim to provide a pressure mapping using the current carrying and voltage sensing electrodes attached to the boundary of the fabric patch. Pressure-induced shape change over the sensor area makes a change in the conductivity distribution which can be conveyed to the change of boundary current-voltage data. This boundary data is obtained through electrode measurements in EIT system. The corresponding inverse problem is to reconstruct the pressure and deformation map from the relationship between the applied current and the measured voltage on the fabric boundary. Taking advantage of EIT in providing dynamical images of conductivity changes due to pressure induced shape change, the pressure map can be estimated. In this paper, the EIT-based fabric sensor was presented for circular and rectangular sensor geometry. A stretch sensitive fabric was used in circular sensor with 16 electrodes and a pressure sensitive fabric was used in a rectangular sensor with 32 electrodes. A preliminary human test was carried out with the rectangular sensor for foot pressure mapping showing promising results.
PMCID: PMC3600212  PMID: 23533538
10.  Characterization of Cellulolytic and Xylanolytic Enzymes of Bacillus licheniformis JK7 Isolated from the Rumen of a Native Korean Goat 
A facultative bacterium producing cellulolytic and hemicellulolytic enzymes was isolated from the rumen of a native Korean goat. The bacterium was identified as a Bacillus licheniformis on the basis of biochemical and morphological characteristics and 16S rDNA sequences, and has been designated Bacillus licheniformis JK7. Endoglucanase activities were higher than those of β-glucosidase and xylanase at all temperatures. Xylanase had the lowest activity among the three enzymes examined. The optimum temperature for the enzymes of Bacillus licheniformis JK7 was 70°C for endoglucanase (0.75 U/ml) and 50°C for β-glucosidase and xylanase (0.63 U/ml, 0.44 U/ml, respectively). All three enzymes were stable at a temperature range of 20 to 50°C. At 50°C, endoglucanse, β-glucosidase, and xylanase had 90.29, 94.80, and 88.69% residual activity, respectively. The optimal pH for the three enzymes was 5.0, at which their activity was 1.46, 1.10, and 1.08 U/ml, respectively. The activity of all three enzymes was stable in the pH range of 3.0 to 6.0. Endoglucanase activity was increased 113% by K+, while K+, Zn+, and tween 20 enhanced β-glucosidase activity. Xylanase showed considerable activity even in presence of selected chemical additives, with the exception of Mn2+ and Cu2+. The broad range of optimum temperatures (20 to 40°C) and the stability under acidic pH (4 to 6) suggest that the cellulolytic enzymes of Bacillus licheniformis JK7 may be good candidates for use in the biofuel industry.
PMCID: PMC4093055  PMID: 25049705
Bacillus licheniformis; Endoglucanase; β-Glucosidase; Xylanase; Goat
11.  Effects of Synchronization of Carbohydrate and Protein Supply in Total Mixed Ration with Korean Rice Wine Residue on Ruminal Fermentation, Nitrogen Metabolism and Microbial Protein Synthesis in Holstein Steers 
Three Holstein steers in the growing phase, each with a ruminal cannula, were used to test the hypothesis that the synchronization of the hourly rate of carbohydrate and nitrogen (N) released in the rumen would increase the amount of retained nitrogen for growth and thus improve the efficiency of microbial protein synthesis (EMPS). In Experiment 1, in situ degradability coefficients of carbohydrate and N in feeds including Korean rice wine residue (RWR) were determined. In Experiment 2, three total mixed ration (TMR) diets having different rates of carbohydrate and N release in the rumen were formulated using the in situ degradability of the feeds. All diets were made to contain similar contents of crude protein (CP) and neutral detergent fiber (NDF) but varied in their hourly pattern of nutrient release. The synchrony index of the three TMRs was 0.51 (LS), 0.77 (MS) and 0.95 (HS), respectively. The diets were fed at a restricted level (2% of the animal’s body weight) in a 3×3 Latin-square design. Synchronizing the hourly supply of energy and N in the rumen did not significantly alter the digestibility of dry matter, organic matter, crude protein, NDF or acid detergent fiber (ADF) (p>0.05). The ruminal NH3-N content of the LS group at three hours after feeding was significantly higher (p<0.05) than that of the other groups; however, the mean values of ruminal NH3-N, pH and VFA concentration among the three groups were not significantly different (p>0.05). In addition, the purine derivative (PD) excretion in urine and microbial-N production (MN) among the three groups were not significantly different (p>0.05). In conclusion, synchronizing dietary energy and N supply to the rumen did not have a major effect on nutrient digestion or microbial protein synthesis (MPS) in Holstein steers.
PMCID: PMC4093039  PMID: 25049518
By-product; Dairy Steer; Microbial Protein Synthesis; Purine Derivative; Rice Wine Residue; Synchronization)
12.  Multimodality imaging in the surgical treatment of children with nonlesional epilepsy 
Neurology  2011;76(1):41-48.
To evaluate the diagnostic value of individual noninvasive presurgical modalities and to study their role in surgical management of nonlesional pediatric epilepsy patients.
We retrospectively studied 14 children (3–18 years) with nonlesional intractable focal epilepsy. Clinical characteristics, surgical outcome, localizing features on 3 presurgical diagnostic tests (subtraction peri-ictal SPECT coregistered to MRI [SISCOM], statistical parametric mapping [SPM] analysis of [18F] FDG-PET, magnetoencephalography [MEG]), and intracranial EEG (iEEG) were reviewed. The localization of each individual test was determined for lobar location by visual inspection. Concordance of localization between each test and iEEG was scored as follows: 2 = lobar concordance; 1 = hemispheric concordance; 0 = discordance or nonlocalization. Total concordance score in each patient was measured by the summation of concordance scores for all 3 tests.
Seven (50%) of 14 patients were seizure-free for at least 12 months after surgery. One (7%) had only rare seizures and 6 (43%) had persistent seizures. MEG (79%, 11/14) and SISCOM (79%, 11/14) showed greater lobar concordance with iEEG than SPM-PET (13%, 3/14) (p < 0.05). SPM-PET provided hemispheric lateralization (71%, 10/14) more often than lobar localization. Total concordance score tended to be greater for seizure-free patients (4.7) than for non–seizure-free patients (3.9).
Our data suggest that MEG and SISCOM are better tools for lobar localization than SPM analysis of FDG-PET in children with nonlesional epilepsy. A multimodality approach may improve surgical outcome as well as selection of surgical candidates in patients without MRI abnormalities.
PMCID: PMC3030221  PMID: 21205694
13.  Preferences regarding Genetic Research Results: Comparing Veterans and Nonveterans Responses 
Public Health Genomics  2010;13(7-8):431-439.
Communicating genetic research results to participants presents ethical challenges. Our objectives were to examine participants’ preferences in receiving future genetic research results and to compare preferences reported by veteran and nonveterans participants.
Secondary analysis was performed on data collected in 2000–2004 from 1,575 consent forms signed by Mexican-American participants enrolled in 2 genetic family studies (GFS) in San Antonio: The Family Investigation of Nephropathy and Diabetes (FIND) and the Extended FIND (EFIND). The consent forms for these studies contained multiple-choice questions to examine participants’ preferences about receiving their (1) clinical lab results and (2) future genetic research results. The FIND and EFIND databases had information on subjects’ demographic characteristics and some selected clinical variables. We identified veterans using the Veterans Health Administration's (VHA's) centralized data repository. We compared veterans’ and nonveterans’ preferences using Student's t test for continuous variables and χ2 test for discrete variables. A logistic regression analyzed subjects’ preference for receiving their research results, controlling for other socio-demographic and clinical variables.
The sample included 275 (18%) veterans and 1,247 (82%) nonveterans. Our results indicated a strong desire among the majority of participants 1,445 (95%) in getting their clinical lab research results. Likewise, 93% expressed interest in being informed about their future genetic results. There was no significant difference in veterans’ and nonveterans’ preference to disclosure of the research results (χ2 test; p > 0.05). Regression analysis showed no significant relationship (p = 0.449) between the outcome (receiving research results) and veterans’ responses after controlling for demographics and educational levels.
Participants believed they would prefer receiving their genetic research results. Veterans are similar to nonveterans in their preferences. Offering genetic research results to participants should be based on well defined and structured plans to enhance interpretation of genetic data.
PMCID: PMC3025894  PMID: 20829581
Common complex diseases; Ethics; Genetic family studies; Research results
14.  Radiological findings and clinical features of thoracic immunoglobulin G4-positive plasma cell granuloma: two cases 
The British Journal of Radiology  2010;83(991):e150-e153.
Plasma cell granulomas, inflammatory pseudotumours and myofibroblastomas are synonymous with characteristic plasma cell infiltration in various body organs including the pancreas, liver, retroperitoneum and mediastinal structures causing idiopathic fibrosclerosis. Recently, a new concept has arisen regarding the relationship between immunoglobulin (Ig)G4-positive cell infiltration and idiopathic systemic fibrosclerosis. We report two cases showing IgG4-positive cell infiltration in the lung presenting as lung nodules with or without extrapulmonary manifestations.
PMCID: PMC3473664  PMID: 20603401
16.  Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study 
We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients.
Materials and methods:
The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of ≥ 8 voids per 24 h and episodes of urgency or urgency incontinence ≥ 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King’s Health Questionnaire.
A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively).
Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.
PMCID: PMC2680337  PMID: 19143854
17.  A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer 
British Journal of Cancer  2007;96(10):1514-1519.
Capecitabine, a prodrug of 5-FU, has been reported to generate maximal tumour activity at tumour sites and/or to improve drug tolerability as compared with 5-FU infusion, and it has also been demonstrated to act synergistically with irinotecan against some solid cancers. A previous study concluded that dose-intensified biweekly capecitabine seems to be more effective at increasing both response rate and progression-free survival time than conventional dose and schedule of capecitabine in colon cancer. We conducted this study to ascertain the efficacy and toxicity of dose-intensified biweekly capecitabine and irinotecan combination chemotherapy in chemotherapy-naïve advanced or metastatic gastric cancer patients. Patients were treated with irinotecan 130 mg m−2 intravenously for 90 min on days 1 and 15. Capecitabine at 3500 mg m−2 day−1, divided into two sessions per day, was administered for seven consecutive days from days 1 and 15, and followed by a 7-day drug-free period, respectively. Fifty-five eligible patients were enrolled in this study from November 2003 to April 2006. There were 22 women and 33 men: median patient age was 54 years (range: 27–81). A total of 200 treatment cycles were administered at a median number of four per patient (range: 1–9). Intent-to-treatment analysis showed that one patient achieved complete response (1.8%), 23 partial response (41.8%), 15 stable disease (27.3%), 10 progressive disease (18.2%) and 6 were non-evaluable (10.9%). The overall response rate was 43.6% (95% confidence interval: 30.2–56.9). The common grade 3–4 toxicities were neutropenia in 12 (21.8%), nausea/vomiting in 3 (5.4%) and diarrhea in 4 (7.2%) patients. Median time to progression was 5 months (range: 0.5–11 months), median survival duration was 11 months (range: 0.5–45 months) and median response duration was 6 months (range: 0.5–9 months). Biweekly dose-intensified capecitabine and irinotecan combination chemotherapy was active for the treatment of advanced or metastatic gastric cancers with a tolerable safety profile.
PMCID: PMC2359951  PMID: 17473829
irinotecan; capecitabine; stomach neoplasms
18.  Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease 
Clinical Endocrinology  2008;68(4):555-560.
Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults.
One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography.
Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62·8 ± 16·0 mg/l vs. 51·7 ± 14·6 mg/l, P < 0·0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0·0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0·3097, P = 0·0002).
Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.
PMCID: PMC2344088  PMID: 17941908
19.  A Suprachoroidal Electrical Retinal Stimulator Design for Long-Term Animal Experiments and In Vivo Assessment of Its Feasibility and Biocompatibility in Rabbits 
This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes.
PMCID: PMC2246081  PMID: 18317521
20.  Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer 
British Journal of Cancer  2005;92(5):827-831.
We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m−2 intravenously (i.v.) for 1 h and then cisplatin 75 mg m−2 i.v. for 2 h on day 1. Oral UFT at 400–600 mg day−1, as determined by body surface area, and leucovorin at 75 mg day−1 were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4–63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6–152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer.
PMCID: PMC2361894  PMID: 15726097
docetaxel; cisplatin; UFT; stomach neoplasms
21.  Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women 
British Journal of Cancer  2003;88(5):675-678.
PMCID: PMC2376333  PMID: 12618873
CYP19; CYP1B1; alcohol; breast cancer
22.  Bcl-2 expression in sputum eosinophils in patients with acute asthma 
Thorax  2000;55(5):370-374.
BACKGROUND—Eosinophils play a pivotal role in asthmatic airway inflammation. Apoptosis is thought to be critically relevant in promoting the clearance of inflammatory cells and the resolution of inflammation. Bcl-2 inhibits apoptosis in cellular systems. A study was undertaken to determine whether bcl-2 expression in sputum reflects the clinical severity of patients with asthma. The relationship between bcl-2 expression in sputum eosinophils and eosinophil activation markers such as interleukin (IL)-5 and eosinophil cationic protein (ECP) levels in sputum supernatant was evaluated.
METHODS—Sputum was obtained from 18 patients with asthma. Fresh expectorated sputum separated from saliva was treated with an equal volume of dithiothreitol 0.1%, cytospun for cell differentials and bcl-2 stain, and the supernatant was collected for biochemical assay. Bcl-2+ eosinophils were stained using immunocytochemistry, ECP was measured by fluoroimmunoassay, and IL-5 was detected by sandwich enzyme linked immunosorbant assay.
RESULTS—Twelve patients with severe or life threatening asthma had more bcl-2+ eosinophils (mean difference 46.8% (95% CI 27.0 to 66.6), p<0.01) and a higher ECP level (p<0.01) in the sputum than those with mild to moderate asthma (n = 6). IL-5 was frequently detected in patients with severe or life threatening asthma (11/12 versus 1/6, p<0.01). There was a significant positive correlation between bcl-2+ eosinophils and ECP levels (r = 0.61, p<0.01) and between bcl-2+ eosinophils and IL-5 levels (r = 0.83, p<0.01). There was a significant negative correlation between bcl-2+ eosinophils and FEV1/FVC (r = -0.54, p<0.05).
CONCLUSION—The increased expression of bcl-2 in eosinophils from sputum of subjects with severe asthma suggests that bcl-2 may prolong survival and decrease apoptosis of airway eosinophils in asthma.

PMCID: PMC1745763  PMID: 10770817
23.  Pulmonary lymphangioleiomyomatosis in Korea 
Thorax  1999;54(7):618-621.
BACKGROUND—Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment. In Korea the first case was reported in 1984 and by 1997 a total of 23 cases had been reported. The clinical findings of these Korean cases are reviewed.
METHODS—The details of 10 cases of LAM on file at Seoul National University Hospital were reviewed together with those of 13 cases previously reported from other Korean institutes. Two, including the only one to be reported in a man, were excluded after reviewing the clinical, radiological, and pathological findings, leaving a total of 21 cases in the present study.
RESULTS—All 21 patients were women and in all cases the disease was proven pathologically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The most common symptoms were dyspnoea and pneumothorax which were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary function tests showed decreased transfer factor (TLCO) (100%) and airflow limitation (67%). All the cases had characteristic cysts on high resolution computed tomographic (HRCT) scanning. The overall severity score based on HRCT scans correlated with the percentage predicted TLCO/VA (p = 0.03) and FEV1/FVC (p = 0.02). The patients were all treated with medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable change clinically or in lung function on medroxyprogesterone and/or tamoxifen, but the remaining patients all deteriorated with two dying of respiratory insufficiency and one of infection following lung transplantation.
CONCLUSIONS—As in other countries, in Korea LAM occurs exclusively in women and progresses despite hormonal treatment.

PMCID: PMC1745515  PMID: 10377208
24.  Epithelioid angiosarcoma of the pleura: a case report. 
Journal of Korean Medical Science  2001;16(6):792-795.
Angiosarcomas of the pleura are very rare tumors and it is difficult to differentiate them from other common pleural tumors such as mesothelioma and metastasic carcinoma clinically and pathologically. We report a case of a young Korean woman with angiosarcoma arising in the pleura. A 34-yr-old woman presented with dyspnea and chest tightness and pain for several months. A computed tomographic scan of the chest showed diffuse thickening of the left pleura and effusion with passive atelectasis. At thoracotomy the left pleura was thick and indurated. Histologically, the decorticated pleura revealed infiltration of sheets or cords of polygonal and epithelioid tumor cells showing rudimentary vascular differentiation. Immunohistochemically, the tumor cells were strongly positive for CD31, CD34, and vimentin, whereas weakly positive for factor VIII, and negative for cytokeratin, which are characteristic and specific findings of angiosarcoma.
PMCID: PMC3054810  PMID: 11748365
25.  Expression of NF-kappaB and cytokines in chronic rejection of transplanted murine heart. 
Journal of Korean Medical Science  2001;16(4):397-406.
The heart transplantation-associated accelerated graft arteriosclerosis (AGAS) is one of the major causes of cardiac allograft failure. We investigated the early time-course of expresssion patterns of cytokines, transcription factor, and its inhibitor in the intraabdominally transplanted mice hearts that differed only in the D locus of class I histocompatibility antigen. The allograft hearts were harvested at 1-3, 5, 7, 14, 28, and 42 days after the transplantation, and the expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) were examined in these specimens. The expressions of TNF-alpha and INF-gamma were observed on day 1, peaking on day 5 and 7, respectively. Activated NF-kappaB (p65) expression was present on the cytoplasm and perinuclear area in the endothelial cells of coronary arteries on day 1. The peak of translocation of NF-B from cytoplasm to nucleus appeared on day 5 in the endothelial cells, myocytes, and leukocytes within the vessels, and remained elevated until day 42. The I-kappaB expression gradually increased from day 1 until day 5, but a remarkable decrease was detected on day 7. Our data suggest that the increased expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) play an important role in inducing immune responses in the donor allograft heart and hence the blockage of the expressions might be mandatory to avoid a potential graft failure.
PMCID: PMC3054775  PMID: 11511783

Results 1-25 (59)