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1.  In vivo cancer imaging by poly(ethylene glycol)-b-poly(ε-caprolactone) micelles containing a near-infrared probe 
Nanomedicine  2011;8(2):228-236.
Non-invasive near infrared (NIR) fluorescence imaging is a promising technique for the intra-operative assessment of solid tumor removal. We incorporated a lipophilic NIR probe, 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide (DiR), in poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) micelles, resulting in DiR solubilization in water, occupying nanoscopic PEG-b-PCL micelles. DiR in a self-quenched or non-quenched state showed different kinetics of release from PEG-b-PCL micelles in vitro; however, both obtained high tumor delineation (tumor-to-muscle ratio of 30-43 from collected organs). These results suggest that PEG-b-PCL micelles with DiR are a promising nano-sized imaging agent that will provide a basis for enhanced surgical guidance via NIR visualization of tumors.
doi:10.1016/j.nano.2011.06.009
PMCID: PMC3193583  PMID: 21704593
Near infrared (NIR) fluorescence imaging; Poly(ethylene glycol)-b-poly(ε-caprolactone); Polymeric micelles; Self-quenching
2.  Short Segment Fixation for Thoracolumbar Burst Fracture Accompanying Osteopenia : A Comparative Study 
Objective
The purpose of this study was to compare the results of three types of short segment screw fixation for thoracolumbar burst fracture accompanying osteopenia.
Methods
The records of 70 patients who underwent short segment screw fixation for a thoracolumbar burst fracture accompanying osteopenia (-2.5< mean T score by bone mineral densitometry <-1.0) from January 2005 to January 2008 were reviewed. Patients were divided into three groups based on whether or not bone fusion and bone cement augmentation procedure 1) Group I (n=26) : short segment fixation with posterolateral bone fusion; 2) Group II (n=23) : bone cement augmented short segment fixation with posterolateral bone fusion; 3) Group III (n=21) : bone cement augmented, short segment percutaneous screw fixation without bone fusion. Clinical outcomes were assessed using a visual analogue scale and modified MacNab's criteria. Radiological findings, including kyphotic angle and vertebral height, and procedure-related complications, such as screw loosening or pull-out, were analyzed.
Results
No significant difference in radiographic or clinical outcomes was noted between patients managed using the three different techniques at last follow up. However, Group I showed more correction loss of kyphotic deformities and vertebral height loss at final follow-up, and Group I had higher screw loosening and implant failure rates than Group II or III.
Conclusion
Bone cement augmented procedure can be an efficient and safe surgical techniques in terms of achieving better outcomes with minimal complications for thoracolumbar burst fracture accompanying osteopenia.
doi:10.3340/jkns.2013.53.1.26
PMCID: PMC3579078  PMID: 23440679
Burst fracture; Osteopenia; Fusion
3.  Simultaneous determination of methylcarbamate and ethylcarbamate in fermented foods and beverages by derivatization and GC-MS analysis 
Background
Methylcarbamate (MC) and ethylcarbamate (EC) are toxic compounds that commonly exist in fermented food and beverages. In order to estimate the risk for their exposure, a sensitive simultaneous analytical method is required
Results
A simultaneous determination of MC and EC was described based on derivatization with 9-xanthydrol and consecutive detection using gas chromatography–mass spectrometry. The derivatization of MC and EC was performed directly in food or beverages and the reaction conditions were established through changing various parameters. The detection and the quantification limits were 0.01-0.03 μg/kg and 0.03-0.1 μg/kg, respectively, and the interday relative standard deviation was less than 12% at concentrations of 2.0 and 50 μg/kg. MC and EC were measured from 0.4 μg/kg to 85.8 μg/kg in sixteen Korean fermented foods and eleven beverages.
Conclusion
A simple, sensitive method to detect MC and EC in several solid foods and liquid foods was developed based on derivatization with 9-xanthydrol for 10 min at an ambient temperature. The method may useful for routine analysis of MC and EC in numerous food samples.
doi:10.1186/1752-153X-6-157
PMCID: PMC3537662  PMID: 23234430
Methylcarbamate; Ethylcarbamate; Fermented food; Beverages; GC-MS
4.  Binding of Hanatoxin to the Voltage Sensor of Kv2.1 
Toxins  2012;4(12):1552-1564.
Hanatoxin 1 (HaTx1) is a polypeptide toxin isolated from spider venoms. HaTx1 inhibits the voltage-gated potassium channel kv2.1 potently with nanomolar affinities. Its receptor site has been shown to contain the S3b-S4a paddle of the voltage sensor (VS). Here, the binding of HaTx1 to the VSs of human Kv2.1 in the open and resting states are examined using a molecular docking method and molecular dynamics. Molecular docking calculations predict two distinct binding modes for the VS in the resting state. In the two binding modes, the toxin binds the S3b-S4a from S2 and S3 helices, or from S1 and S4 helices. Both modes are found to be stable when embedded in a lipid bilayer. Only the mode in which the toxin binds the S3b-S4a paddle from S2 and S3 helices is consistent with mutagenesis experiments, and considered to be correct. The toxin is then docked to the VS in the open state, and the toxin-VS interactions are found to be less favorable. Computational mutagenesis calculations performed on F278R and E281K mutant VSs show that the mutations may reduce toxin binding affinity by weakening the non-bonded interactions between the toxin and the VS. Overall, our calculations reproduce a wide range of experimental data, and suggest that HaTx1 binds to the S3b-S4a paddle of Kv2.1 from S2 and S3 helices.
doi:10.3390/toxins4121552
PMCID: PMC3528262  PMID: 23250329
hanatoxin; Kv2.1; voltage sensor; gating modifier toxin; molecular dynamics
5.  Expression of intestinal transporter genes in beagle dogs 
This study was performed to produce a transcriptional database of the intestinal transporters of beagle dogs. Total RNA was isolated from the duodenum and the expression of various mRNAs was measured using GeneChip® oligonucleotide arrays. A total of 124 transporter genes were detected. Genes for fatty acid, peptide, amino acid and glucose and multidrug resistance/multidrug resistance-associated protein (MDR/MRP) transport were expressed at relatively higher levels than the other transporter types. The dogs exhibited abundant mRNA expression of the fatty acid transporters (fatty acid binding proteins, FABPs) FABP1 and FABP2, the ATP-binding cassettes (ABCs) ABCB1A and ABCC2, the amino acid/peptide transporters SLC3A1 and SLC15A1, the glucose transporters SLC5A1, SLC2A2 and SLC2A5, the organic anion transporter SLC22A9 and the phosphate transporters SLC20A1 and SLC37A4. In mice, a similar profile was observed with high expression of the glucose transporters SLC5A1 and SLC2As, the fatty acid transporters FABP1 and FABP2, the MDR/MRP transporters ABCB1A and ABCC2 and the phosphate transporter SLC37A4. However, the overall data reveal diverse transcriptomic profiles of the intestinal transporters of dogs and mice. Therefore, the current database may be useful for comparing the intestinal transport systems of dogs with those of mice to better evaluate xenobiotics.
doi:10.3892/etm.2012.777
PMCID: PMC3524273  PMID: 23251289
gene expression; transporters; intestine; dog
6.  Structural Basis of the Selective Block of Kv1.2 by Maurotoxin from Computer Simulations 
PLoS ONE  2012;7(10):e47253.
The 34-residue polypeptide maurotoxin (MTx) isolated from scorpion venoms selectively inhibits the current of the voltage-gated potassium channel Kv1.2 by occluding the ion conduction pathway. Here using molecular dynamics simulation as a docking method, the binding modes of MTx to three closely related channels (Kv1.1, Kv1.2 and Kv1.3) are examined. We show that MTx forms more favorable electrostatic interactions with the outer vestibule of Kv1.2 compared to Kv1.1 and Kv1.3, consistent with the selectivity of MTx for Kv1.2 over Kv1.1 and Kv1.3 observed experimentally. One salt bridge in the bound complex of MTx-Kv1.2 forms and breaks in a simulation period of 20ns, suggesting the dynamic nature of toxin-channel interactions. The toxin selectivity likely arises from the differences in the shape of the channel outer vestibule, giving rise to distinct orientations of MTx on block. Potential of mean force calculations show that MTx blocks Kv1.1, Kv1.2 and Kv1.3 with an IC50 value of 6 µM, 0.6nM and 18 µM, respectively.
doi:10.1371/journal.pone.0047253
PMCID: PMC3468451  PMID: 23071772
7.  Clinical significance of standardized uptake value and maximum tumor diameter in patients with primary extranodal diffuse large B cell lymphoma 
The Korean Journal of Hematology  2012;47(3):207-212.
Background
Maximum standardized uptake value (SUVmax) and maximum tumor diameter (MTD) have been shown to reflect survival outcome in diffuse large B cell lymphoma (DLBCL). However, applying these values to primary extranodal DLBCL is difficult because they are separate nosological entities with differences in genetic origin. We therefore decided to evaluate whether SUVmax and MTD on 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18-FDG) positron emission tomography (PET) would affect the survival outcome in primary extranodal DLBCL.
Methods
From October 2005 to November 2010, 76 primary extranodal DLBCL patients receiving R-CHOP therapy were analyzed. All patients had undergone an initial 18-FDG PET/CT and conventional computed tomography (CT) of the neck, chest, abdomen, and pelvis for staging. Median follow-up period was 35 months.
Results
The SUVmax and MTD cut-off values were 11.0 and 7.5 cm, respectively. SUVmax≥11.0 predicted a short progression free survival (PFS, P=0.002) and overall survival (OS, P=0.002). MTD≥7.5 cm was associated with poor PFS (P=0.003) and OS (P=0.003). High International Prognostic Index (IPI) was also associated with the survival outcome (PFS, P=0.046; OS, P=0.030). Multivariate analysis revealed that SUVmax≥11.0 (PFS, hazard ratio [HR]=10.813, P=0.024; OS, HR=6.312, P=0.015); MTD≥7.5 cm (PFS, HR=5.631, P=0.008; OS, HR=4.072, P=0.008); and high IPI (PFS, P=0.027; OS, P=0.046) were independent prognostic factors.
Conclusion
It appears that both MTD and SUVmax can be independent prognostic factors in primary extranodal DLBCL.
doi:10.5045/kjh.2012.47.3.207
PMCID: PMC3464338  PMID: 23071476
Lymphoma; Large B-cell; Extranodal
8.  Does Fibrin Sealant Reduce Seroma after Immediate Breast Reconstruction Utilizing a Latissimus Dorsi Myocutaneous Flap? 
Archives of Plastic Surgery  2012;39(5):504-508.
Background
The most common complication of latissimus dorsi myocutaneous flap in breast reconstruction is seroma formation in the back. Many clinical studies have shown that fibrin sealant reduces seroma formation. We investigated any statistically significant differences in postoperative drainage and seroma formation when utilizing the fibrin sealant on the site of the latissimus dorsi myocutaneous flap harvested for immediate breast reconstruction after skin-sparing partial mastectomy.
Methods
A total of 46 patients underwent immediate breast reconstruction utilizing a latissimus dorsi myocutaneous island flap. Of those, 23 patients underwent the procedure without fibrin sealant and the other 23 were administered the fibrin sealant. All flaps were elevated with manual dissection by the same surgeon and were analyzed to evaluate the potential benefits of the fibrin sealant. The correlation analysis and Mann-Whitney U test were used for analyzing the drainage volume according to age, weight of the breast specimen, and body mass index.
Results
Although not statistically significant, the cumulative drainage fluid volume was higher in the control group until postoperative day 2 (530.1 mL compared to 502.3 mL), but the fibrin sealant group showed more drainage beginning on postoperative day 3. The donor site comparisons showed the fibrin sealant group had more drainage beginning on postoperative day 3 and the drain was removed 1 day earlier in the control group.
Conclusions
The use of fibrin sealant resulted in no reduction of seroma formation. Because the benefits of the fibrin sealant are not clear, the use of fibrin sealant must be fully discussed with patients before its use as a part of informed consent.
doi:10.5999/aps.2012.39.5.504
PMCID: PMC3474408  PMID: 23094246
Seroma; Fibrin tissue adhesive; Mastectomy
9.  Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL) 
Background
The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.
Methods
Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.
Results
Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001).
Conclusions
Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.
doi:10.1186/1756-8722-5-49
PMCID: PMC3445827  PMID: 22889180
Primary adrenal lymphoma; Diffuse large B-cell lymphoma; Prognostic factor; R-CHOP
10.  The Effect of Methanol on the Structural Parameters of Neuronal Membrane Lipid Bilayers 
The structures of the intact synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortexs, and the outer and the inner monolayer separately, were evaluated with 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) as fluorescent reporters and trinitrophenyl groups as quenching agents. The methanol increased bulk rotational and lateral mobilities of SPMVs lipid bilayers. The methanol increased the rotational and lateral mobilities of the outer monolayers more than of the inner monolayers. n-(9-Anthroyloxy)stearic acid (n-AS) were used to evaluate the effect of the methanol on the rotational mobility at the 16, 12, 9, 6, and 2 position of aliphatic chains present in phospholipids of the SPMVs outer monolayers. The methanol decreased the anisotropy of the 16-(9-anthroyloxy)palmitic acid (16-AP), 12-(9-anthroyloxy)stearic acid (12-AS), 9-(9-anthroyloxy)stearic acid (9-AS), and 6-(9-anthroyloxy)stearic acid (6-AS) in the SPMVs outer monolayer but it increased the anisotropy of 2-(9-anthroyloxy)stearic acid (2-AS) in the monolayers. The magnitude of the increased rotational mobility by the methanol was in the order at the position of 16, 12, 9, and 6 of aliphatic chains in phospholipids of the outer monolayers. Furthermore, the methanol increased annular lipid fluidity and also caused membrane proteins to cluster. The important finding is that was far greater increase by methanol in annular lipid fluidity than increase in lateral and rotational mobilities by the methanol. Methanol alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that methanol, in additions to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membranes lipids.
doi:10.4196/kjpp.2012.16.4.255
PMCID: PMC3419761  PMID: 22915991
Annular lipid fluidity; Membrane protein clustering; Methanol; Neuronal membranes; Transbilayer lateral and rotational mobility
11.  C-Terminal Substitution of HBV Core Proteins with Those from DHBV Reveals That Arginine-Rich 167RRRSQSPRR175 Domain Is Critical for HBV Replication 
PLoS ONE  2012;7(7):e41087.
To investigate the contributions of carboxyl-terminal nucleic acid binding domain of HBV core (C) protein for hepatitis B virus (HBV) replication, chimeric HBV C proteins were generated by substituting varying lengths of the carboxyl-terminus of duck hepatitis B virus (DHBV) C protein for the corresponding regions of HBV C protein. All chimeric C proteins formed core particles. A chimeric C protein with 221–262 amino acids of DHBV C protein, in place of 146–185 amino acids of the HBV C protein, supported HBV pregenomic RNA (pgRNA) encapsidation and DNA synthesis: 40% amino acid sequence identity or 45% homology in the nucleic-acid binding domain of HBV C protein was sufficient for pgRNA encapsidation and DNA synthesis, although we predominantly detected spliced DNA. A chimeric C protein with 221–241 and 251–262 amino acids of DHBV C, in place of HBV C 146–166 and 176–185 amino acids, respectively, could rescue full-length DNA synthesis. However, a reciprocal C chimera with 242–250 of DHBV C (242RAGSPLPRS250) introduced in place of 167–175 of HBV C (167RRRSQSPRR175) significantly decreased pgRNA encapsidation and DNA synthesis, and full-length DNA was not detected, demonstrating that the arginine-rich 167RRRSQSPRR175 domain may be critical for efficient viral replication. Five amino acids differing between viral species (underlined above) were tested for replication rescue; R169 and R175 were found to be important.
doi:10.1371/journal.pone.0041087
PMCID: PMC3401125  PMID: 22911745
12.  Alternative Treatment of Osteoma Using an Endoscopic Holmium-YAG Laser 
Archives of Plastic Surgery  2012;39(4):422-425.
Osteoma is one of the most common tumors of the cranial vault and the facial skeleton. For osteoma in the facial region, endoscopic resection is widely used to prevent surgical scarring. Tumors in a total of 14 patients were resected using an endoscopic holmium-doped yttrium aluminium garnet (Ho:YAG) laser with a long flexible fiber. Aside from having the advantage of not leaving a scar due to the use of endoscopy, this procedure allowed resection at any position, was minimally invasive, and caused less postoperative pain. This method yielded excellent cosmetic results, so the endoscopic Ho:YAG laser is expected to emerge as a good treatment option for osteoma.
doi:10.5999/aps.2012.39.4.422
PMCID: PMC3408291  PMID: 22872849
Endoscopy; Holmium; Osteoma
13.  Bronchoscopic Ethanolamine Injection Therapy in Patients with Persistent Air Leak from Chest Tube Drainage 
Background
Chest tube drainage (CTD) is an indication for the treatment of pneumothorax, hemothroax and is used after a thoracic surgery. But, in the case of incomplete lung expansion, and/or persistent air leak from CTD, medical or surgical thoracoscopy or, if that is unavailable, limited thoracotomy, should be considered. We evaluate the efficacy of bronchoscopic injection of ethanolamine to control the persistent air leak in patients with CTD.
Methods
Patients who had persistent or prolonged air leak from CTD were included, consecutively. We directly injected 1.0 mL solution of 5% ethanolamine oleate into a subsegmental or its distal bronchus, where it is a probable air leakage site, 1 to 21 times using an injection needle through a fiberoptic bronchoscope.
Results
A total of 15 patients were enrolled; 14 cases of spontaneous pneumothorax [idiopathic 9, chronic obstructive pulmonary disease (COPD) 3, post-tuberculosis 2] and one case of empyema associated with broncho-pleural fistula. Of these, five were patients with persistent air leak from CTD, just after a surgical therapy, wedge resection with plication for blebs or bullae. With an ethanolamine injection therapy, 12 were successful but three (idiopathic, COPD and post-tuberculosis) failed, and were followed by a surgery (2 cases) or pleurodesis (1 case). Some adverse reactions, such as fever, chest pain and increased radiographic opacities occurred transiently, but resolved without any further events. With success, the time from the procedure to discharge was about 3 days (median).
Conclusion
Bronchoscopic ethanolamine injection therapy may be partially useful in controlling air leakage, and reducing the hospital stay in patients with persistent air leak from CTD.
doi:10.4046/trd.2012.72.5.441
PMCID: PMC3475465  PMID: 23101009
Bronchoscopy; Chest Tubes; Ethanolamine; Pneumothorax
14.  Rapid determination of natural steroidal hormones in saliva for the clinical diagnoses 
Background
Saliva samples are easily collectable and non-invasive, and the monitoring of natural steroidal hormones, such as estrone (E1), 17β-estradiol (E2), estriol (E3), progesterone (P), and testosterone (T), in saliva has attracted much attention due to its numerous potential clinical and health-related applications. Because E1, E2, E3, P and T are useful indicators in numerous clinical and health-related diagnoses, there is a need for simultaneous determination.
Results
A gas chromatography-mass spectrometric assay was developed for rapid simultaneous determination of E1, E2, E3, P and T in saliva for clinical diagnoses. Extraction was achieved with a liquid extraction using 3.0 mL of pentane. The extract was dried and silylated with N-methyl-N-(trimethylsilyl) trifluoroacetamide/NH4I (100:2) under a catalysis of 1.5% dithioerythritol for 10 min at 90°C. The accuracy of the analytes was in the range of 96% to 112% at concentrations of 0.05 and 0.10 μg/L (5.0 and 10.0 μg/L for E3), respectively, with relative standard deviations of less than 11%. The lowest quantification limits were from 0.002 to 0.6 μg/L for 1.0 mL of saliva.
Conclusion
Natural steroidal hormones were detected in the concentration ranges of nd to 0.2 μg/L in human saliva. The salivary testosterone values in the patients with prostatic carcinoma were significantly lower than in normal males. The method may useful in numerous clinical and health-related diagnoses.
doi:10.1186/1752-153X-6-22
PMCID: PMC3351364  PMID: 22452882
Clinical diagnosis; Natural steroidal hormones; Saliva; GC-MS
15.  Feasibility of Non-TBI Conditioning with Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation in Lymphoid Malignancy 
Background/Aims
This retrospective study evaluated the transplantation outcomes of patients with adult lymphoid malignancies who received chemotherapy-based conditioning with busulfan and fludarabine (BuFlu) and busulfan and cyclophosphamide (BuCy2).
Methods
Thirty-eight patients (34 with acute lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for the remaining 24 patients. Eight and 13 patients were high risk disease in the BuCy2 and BuFlu groups, respectively.
Results
The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 56.5% and 55.2% and that of extensive chronic GVHD 17.0% and 55.6% (p = 0.018) for the BuFlu and BuCy2 groups, respectively. The 3-year relapse rate was 27.8% and 31.4% and 3-year overall survival 34.3% and 46.8% for the BuFlu and BuCy2 groups, respectively. Treatment-related mortality (TRM) was significantly lower in the BuFlu group (16.9%) than in the BuCy2 group (57.1%, p = 0.010). In multivariate analyses, the BuFlu regimen was identified as an independent favorable risk factor for TRM (hazard ratio [HR], 0.036; p = 0.017) and extensive chronic GVHD (HR, 0.168; p = 0.034).
Conclusions
Our BuFlu regimen would appear to be an acceptable conditioning option for lymphoid malignancies, including high-risk diseases. It was safely administered with a lower TRM rate than BuCy2 conditioning.
doi:10.3904/kjim.2012.27.1.72
PMCID: PMC3295992  PMID: 22403503
Precursor cell lymphoblastic leukemia-lymphoma; Busulfan; Drug therapy; Fludarabine
16.  The Effect of Platelet-rich Plasma on Wounds of OLETF Rats Using Expression of Matrix Metalloproteinase-2 and -9 mRNA 
Archives of Plastic Surgery  2012;39(2):106-112.
Background
Complicated diabetic patients show impaired, delayed wound healing caused by multiple factors. A study on wound healing showed that platelet-rich plasma (PRP) was effective in normal tissue regeneration. Nonetheless, there is no evidence that when plateletrich plasma is applied to diabetic wounds, it normalizes the diabetic wound healing process. In this study, we have analyzed matrix metalloproteinase (MMP)-2, MMP-9 expression to investigate the effect of PRP on diabetic wounds.
Methods
Twenty-four-week-old male Otsuka Long-Evans Tokushima Fatty rats were provided by the Tokushima Research Institute. At 50 weeks, wounds were arranged in two sites on the lateral paraspinal areas. Each wound was treated with PRP gel and physiologic saline gauze. To determine the expression of MMP-2, MMP-9, which was chosen as a marker of wound healing, reverse transcription polymerase chain reaction (RT-PCR) was performed and local distribution and expression of MMP-2, MMP-9 was also observed throughout the immunohistochemical staining.
Results
RT-PCR and the immunohistochemical study showed that the levels of MMP-2, MMP-9 mRNA expression in PRP applied tissues were higher than MMP-2, MMP-9 mRNA expression in saline-applied tissues. MMP-9 mRNA expression in wounds of diabetic rats decreased after healing began to occur. But no statistical differences were detected on the basis of body weight or fasting blood glucose levels.
Conclusions
This study could indicate the extracellular matrix-regulating effect observed with PRP. Our results of the acceleration of wound healing events by PRP under hyperglycemic conditions might be a useful clue for future clinical treatment for diabetic wounds.
doi:10.5999/aps.2012.39.2.106
PMCID: PMC3385326  PMID: 22783508
Platelet-rich plasma; Rats, OLETF; Matrix mtalloproteinase-2; Matrix metalloproteinase-9
17.  Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells 
Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; 25 µg/ml) and methotrexate (MTX; 50 µg/ml), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptasepolymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.
doi:10.4196/kjpp.2012.16.1.11
PMCID: PMC3298820  PMID: 22416214
Cancer stem cell; 5-FU/MTX; ABCG2/IL-6R/CD133; Drug resistance
18.  Computational Design of a Carbon Nanotube Fluorofullerene Biosensor 
Sensors (Basel, Switzerland)  2012;12(10):13720-13735.
Carbon nanotubes offer exciting opportunities for devising highly-sensitive detectors of specific molecules in biology and the environment. Detection limits as low as 10−11 M have already been achieved using nanotube-based sensors. We propose the design of a biosensor comprised of functionalized carbon nanotube pores embedded in a silicon-nitride or other membrane, fluorofullerene-Fragment antigen-binding (Fab fragment) conjugates, and polymer beads with complementary Fab fragments. We show by using molecular and stochastic dynamics that conduction through the (9, 9) exohydrogenated carbon nanotubes is 20 times larger than through the Ion Channel Switch ICS™ biosensor, and fluorofullerenes block the nanotube entrance with a dissociation constant as low as 37 pM. Under normal operating conditions and in the absence of analyte, fluorofullerenes block the nanotube pores and the polymer beads float around in the reservoir. When analyte is injected into the reservoir the Fab fragments attached to the fluorofullerene and polymer bead crosslink to the analyte. The drag of the much larger polymer bead then acts to pull the fluorofullerene from the nanotube entrance, thereby allowing the flow of monovalent cations across the membrane. Assuming a tight seal is formed between the two reservoirs, such a biosensor would be able to detect one channel opening and thus one molecule of analyte making it a highly sensitive detection design.
doi:10.3390/s121013720
PMCID: PMC3545589  PMID: 23202018
carbon nanotube; biosensor; fluorofullerene; molecular dynamics; distributional molecular dynamics; proof-of-concept
19.  Outcomes of Sleeve Lobectomy versus Pneumonectomy for Lung Cancer 
Background
Sleeve lobectomy for lung cancer in close proximity to or involving the carina is widely accepted. Operative morbidity and mortality rates, recurrence, and survival rates have varied considerably across studies.
Materials and Methods
From March of 2005 to July of 2010, sleeve lobectomy was performed in 19 patients and pneumonectomy was performed in 20 patients. In this paper, the results of sleeve lobectomy and pneumonectomy for patients with lung cancer will be compared and evaluated.
Results
There were no postoperative complications in either group, but there was one mortality in the pneumonectomy group. There was better preservation of pulmonary function in the sleeve lobectomy group than the pneumonectomy group (p=0.066 in FVC, p=0.019 in FEV1). The 3-year survival rates were 46.7% in the sleeve lobectomy group and 54.5% in the pneumonectomy group (p=0.505). The 3-year disease-free survival rates were 38% in the sleeve lobectomy group and 45.8% in the pneumonectomy group (p=0.200).
Conclusion
Sleeve lobectomy for lung cancer showed low mortality, low bronchial anastomotic complication rates, and good preservation of pulmonary function.
doi:10.5090/kjtcs.2011.44.6.413
PMCID: PMC3270283  PMID: 22324026
Lobectomy; Lung; Cancer
20.  Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement 
Annals of Hematology  2011;91(5):697-703.
The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm3 was the cutoff value. The low MTV group (<220 cm3) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (≥220 cm3) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP.
doi:10.1007/s00277-011-1357-2
PMCID: PMC3319905  PMID: 22071570
Diffuse large B cell lymphoma; Positron emission tomography; Rituximab
21.  Minimally Invasive Multi-Level Posterior Lumbar Interbody Fusion Using a Percutaneously Inserted Spinal Fixation System : Technical Tips, Surgical Outcomes 
Objective
There are technical limitations of multi-level posterior pedicle screw fixation performed by the percutaneous technique. The purpose of this study was to describe the surgical technique and outcome of minimally invasive multi-level posterior lumbar interbody fusion (PLIF) and to determine its efficacy.
Methods
Forty-two patients who underwent mini-open PLIF using the percutaneous screw fixation system were studied. The mean age of the patients was 59.1 (range, 23 to 78 years). Two levels were involved in 32 cases and three levels in 10 cases. The clinical outcome was assessed using the visual analog scale (VAS) and Low Back Outcome Score (LBOS). Achievement of radiological fusion, intra-operative blood loss, the midline surgical scar and procedure related complications were also analyzed.
Results
The mean follow-up period was 25.3 months. The mean LBOS prior to surgery was 34.5, which was improved to 49.1 at the final follow up. The mean pain score (VAS) prior to surgery was 7.5 and it was decreased to 2.9 at the last follow up. The mean estimated blood loss was 238 mL (140-350) for the two level procedures and 387 mL (278-458) for three levels. The midline surgical scar was 6.27 cm for two levels and 8.25 cm for three level procedures. Complications included two cases of asymptomatic medial penetration of the pedicle border. However, there were no signs of neurological deterioration or fusion failure.
Conclusion
Multi-level, minimally invasive PLIF can be performed effectively using the percutaneous transpedicular screw fixation system. It can be an alternative to the traditional open procedures.
doi:10.3340/jkns.2011.50.5.441
PMCID: PMC3259464  PMID: 22259691
Posterior lumbar interbody fusion; Percutaneous; Minimally invasive surgery
22.  Naegleria fowleri Lysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells 
Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A 51Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-α, IL-6, and IL-1β, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.
doi:10.3347/kjp.2011.49.3.285
PMCID: PMC3210847  PMID: 22072830
Naegleria fowleri; microglial cell; pro-inflammatory cytokine; cytotoxicity
23.  Prospective Randomization Trial of G-CSF-Primed Induction Regimen versus Standard Regimen in Patients with AML 
Chonnam Medical Journal  2011;47(2):80-84.
The sensitization of leukemia cells with hematopoietic growth factors can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). Therefore, the current trial attempted to evaluate the efficacy of granulocyte colony-stimulating factor (G-CSF) priming in remission induction chemotherapy with an intensified dose of Ara-C for newly diagnosed AML. Patients with newly diagnosed AML were randomly assigned to receive idarubicin (12 mg/m2/24 hr, days 1-3) plus Ara-C (500 mg/m2/12 hr, days 4-8) with G-CSF (250 µg/m2/d, days 3-7) (IAG group) or standard idarubicin (12 mg/m2/24 hr, days 1-3) plus Ara-C (100 mg/m2/12 hr, days 1-7) without G-CSF (IA group). There were no significant differences in sex, age, subtype, or cytogenetic risk between the two groups. Complete remission was achieved in 15 patients (88.2%) from the IAG group and in 14 patients (82.4%) from the IA group (p=0.31). The median time to complete remission was 26 vs. 31 days (p=0.779) for the IA and IAG groups, respectively. The median time to neutrophil recovery (>1×109/L) and platelet recovery (>20×109/L) did not differ significantly between the two groups (26 vs. 26 days, p=0.338; 21 vs. 16 days, p=0.190, respectively). After a median follow-up of 682 days, the 3-year overall survival rate for the IA group was 64.7%, whereas that for the IAG group was 45.6% (p=0.984). No improved clinical outcomes were observed for the AML patients subjected to intensified remission induction with G-CSF priming when compared with standard induction chemotherapy.
doi:10.4068/cmj.2011.47.2.80
PMCID: PMC3214872  PMID: 22111065
Acute myeloid leukemia; Cytarabine; Granulocyte colony-stimulating factor; Induction of remission
24.  Clinical Characteristics of Patients with Medically Unexplained Chronic Widespread Pain: A Primary Care Center Study 
Korean Journal of Family Medicine  2011;32(5):277-284.
Background
Chronic widespread pain (CWP) is known as a common symptom of several organic and psychological disorders. Although medically unexplained CWP (MUE) has lots of clinical distress symptoms, there were no distinct symptoms or signs. Therefore, we conducted this study to investigate clinical distress symptoms of MUE distinct from those of medically explained CWP (ME).
Methods
One hundred nine patients with CWP were enrolled in the study. We classified the study subjects into three groups depending on their medical problems associated with CWP: organic group (ORG), psychological group (PSY), and MUE. All subjects were asked to fill out self-report questionnaires consisting of clinical distress scales including the Korean version of the Fibromyalgia Impact Questionnaire (FIQ-K), fatigue scale, depression scale, and stress scale. And physicians examined 18 tender points over their entire body of the subjects.
Results
MUE patients had higher FIQ-K and fatigue severity scores than ORG patients (all P < 0.05). The average number of tender points were 11.33 in MUE patients, 6.48 in ORG patients and 5.02 in PSY patients and statistically significant (P < 0.0001). There were no statistically different factors between MUE and PSY patients with exception for the number of tender points. Depressive symptom was the highest in PSY patients but not statistically different from MUE patients.
Conclusion
MUE patients had higher physical impairments, fatigue severity and more number of tender points than ORG patients, but had no different clinical characteristics from PSY patients except for the number of tender points.
doi:10.4082/kjfm.2011.32.5.277
PMCID: PMC3383142  PMID: 22745864
Chronic Pain; Fibromyalgia Syndrome; Chronic Fatigue Syndrome
25.  Relationship of serum bilirubin concentration to kidney function and 24-hour urine protein in Korean adults 
BMC Nephrology  2011;12:29.
Background
The relationships among serum bilirubin concentration, kidney function and proteinuria have yet to be fully elucidated, nor have these relationships been investigated in Korean adults.
Method
We retrospectively reviewed the medical records of Korean adults who were evaluated at Kosin University Gospel Hospital (Busan, Republic of Korea) during a five-year period from January 2005 to December 2009. We evaluated the relationships among serum bilirubin concentration, estimated glomerular filtration rate (eGFR) and 24-hour urinary protein excretion in a sample of 1363 Korean adults aged 18 years or older.
Results
The values of eGFR <60 mL/min/1.73 m2 and 24-hour urine albumin ≥150 mg/day were observed in 26.1% (n = 356) and 40.5% (n = 553) of subjects, respectively. Fasting glucose levels ≥126 mg/dL were observed in 44.9% (n = 612) of the total sample. After adjustment for potential confounding factors including demographic characteristics, comorbidities and other laboratory measures, total serum bilirubin was positively associated with eGFR and negatively associated with proteinuria both in the whole cohort and in a subgroup of diabetic individuals.
Conclusions
To our knowledge, this is the first hospital-based study specifically aimed at examining the relationships among serum total bilirubin concentration, 24-hour urine protein and kidney function in Korean adults. We demonstrated that serum total bilirubin concentration was negatively correlated with 24-hour urine protein and positively correlated with eGFR in Korean non-diabetic and diabetic adults.
doi:10.1186/1471-2369-12-29
PMCID: PMC3146921  PMID: 21708045
Proteinuria; Bilirubin; Glomerular filtration rate

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