[Show abstract][Hide abstract] ABSTRACT: Rapid and efficient identification of the geographical origin of Angelica gigas roots (dang-gui) was performed using DART–TOF–MS (direct analysis in real time–time of flight–mass spectrometry) based metabolomics. As an ambient desorption/ionization technique, DART–TOF–MS can provide soft ionization and rapid analysis of samples with little sample preparation so it has been advantageously applied to high-throughput metabolomics analysis. In order to develop an efficient tool for discriminating, particularly geographical origin of raw herbal medicine, we employed DART–TOF–MS fingerprinting on dang-gui from Korean and Chinese markets. Principal component analysis of DART–TOF–MS fingerprints gave distinctive clustering information among two species of A. gigas and A. sinensis so that we used only A. gigas species for the sequential experiment. Orthogonal projections to latent structures-discriminant analysis of A. gigas samples revealed the separation between samples cultivated in two countries. Major discriminating components were elucidated as decursin/decursinol angelate, unidentified molecular ion of m/z 247 (protonated ions of molecular formula of C14H14O4) and another molecular ion of m/z 432. DART–TOF–MS based chemical fingerprinting with the multivariate analysis of dang-gui was shown to be efficient and accurate way to identify its geographical origin, between Korea and China.
[Show abstract][Hide abstract] ABSTRACT: Charcot–Marie–Tooth disease (CMT) is a group of clinically and genetically heterogeneous peripheral neuropathies. We identified two axonal CMT type 2F (CMT2F) families presented with distally predominant weakness in upper and lower extremities with sensory involvement. This study identified a c.404C>T (p.Ser135Phe) mutation in HSPB1 gene as the underlying cause of the both families by applying of whole exome sequencing. The p.Ser135Phe mutation was completely cosegregated with the affected members in the both families, and it was not found in 300 healthy controls. This mutation has been previously reported as the causes of CMT2F or hereditary motor neuropathy 2B (dHMN2B). The mutation was located in the highly conserved alpha-crystallin domain, and several in silico analyses also predicted that the mutation is likely to be pathogenic. HSPB1 encodes heat shock protein 27 (HSP27) which belongs to the superfamily of small stress induced proteins. These results suggest that the HSPB1 mutation is underlying cause of CMT2F phenotype shown in the present families. We believe that this study will be useful for the molecular diagnosis of peripheral neuropathies.
[Show abstract][Hide abstract] ABSTRACT: Thrombocytosis is considered an adverse prognostic factor in various malignancies. However, the clinical significance of thrombocytosis in rectal cancer patients is unknown. We investigated the predictive value of thrombocytosis for pathologic tumor response to preoperative chemoradiotherapy (CRT) and oncologic outcomes in patients with rectal cancer.
Annals of Surgical Oncology 08/2014; · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vancomycin-resistant enterococci (VRE) are one of the leading causes of nosocomial infection at intensive care unit (ICU). Rapid and sensitive detection of VRE infection is in high demand for timely and suitable antibiotic treatment. Here, we optimized a distinct DNA-based diagnostic technique, loop-mediated isothermal amplification (LAMP) for rapid detection of the presence of vanA gene, a critical component of the gene cluster required for vancomycin resistance. Amplification efficiency was optimal at 62 ˚C and with 2mM MgSO4. The detection limit of the DNA template was 80pg and LAMP amplicons were detected within 40min; thereby suggesting a potential applicability of LAMP as a sensitive and urgent diagnostic method. Furthermore, positive LAMP reaction was directly detected with the naked-eye by monitoring the formation of a white precipitate or the color change induced by hydroxyl naphtol blue (HNB) dye. Finally, 56 clinical isolates were successfully tested for the presence of vanA gene by LAMP, which was determined to be more sensitive than PCR. Together, our results clearly demonstrate the usefulness of LAMP for the diagnosis of VRE infection.
Journal of Microbiological Methods 06/2014; · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sarpogrelate HCl (SGL) has been used clinically as an anti-platelet drug for the prevention of thrombus, proliferation of vascular smooth muscle cells and platelet aggregation. This study was to investigate the bioavailability of sustained-release solid dispersion (SR-SD) formulation of SGL to sustain the drug release for up to 24 h. The SR-SD formulations with various drug-to-polymer ratios were prepared by hot-melt coating method. Waxy material carriers such as Compritol 888 ATO and stearyl alcohol were added to SGL and different amounts of HPMC K 15 (HPMC) were mixed. Dissolution profile and bioavailability were compared to SGL powder. Compritol 888 ATO showed the controlling effect of the initial release rate of drug from the formulation and the controlling effect was increased for 24 h by addition of HPMC. As the amount of HPMC increased, the drug release rate from SR-SD decreased because HPMC formed gel layer in aqueous media. Pharmacokinetic study showed that the AUC and Tmax of SGL in SR-SD formulation increased as compared to the SGL powder. These data suggest that the SR-SD formulation effectively controls the drug release rate for 24 h, hoping to be useful for the development of once-a-day formulation of SGL.
Archives of Pharmacal Research 06/2014; · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In search of an ideal method of assisted hatching (AH), we compared the effects of conventional micropipette-AH and laser-AH on the blastocyst formation rate (BFR) and blastocyst cell numbers.
Clinical and experimental reproductive medicine. 06/2014; 41(2):68-74.
[Show abstract][Hide abstract] ABSTRACT: Assuming an association between cancer and metabolism, oncogene-directed metabolic reprogramming in cancer has revealed new target strategies. For example, the LKB1-AMPK-mTOR signaling pathway genes are already known to alter the cell metabolism and to play a critical role in the malignant behavior of cancer. Accordingly, based on the assumption that genetic variations in the LKB1-AMPK-mTOR signaling pathway can change the intracellular signal in terms of metabolic reprogramming, the present study analyzed 18 single nucleotide polymorphisms (SNPs) of the STK11, PRKAA1, TSC1/2, and mTOR genes and their impact on the survival of patients with colorectal cancer.
Seven hundred seventy-two patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Eighteen SNPs were selected from an in silico analysis based on previous evidence of association. The SNP genotyping was performed using a SEQUENOM MassARRAY.
Among the 18 polymorphisms, three SNPs (STK11 rs741765, PRKAA1 rs461404, and TSC1 rs13295634) were significantly associated with disease-free survival (DFS) or overall survival (OS). In a multivariate analysis, the GG genotype of STK11, TT genotype of PRKAA1, and TG or GG genotype of TSC1 were identified as independent prognostic factors for a worse DFS (hazard ratio = 1.398, 1.408, and 1.388; p = 0.030, 0.013, and 0.002, respectively) and OS (hazard ratio = 1.431, 1.680, and 1.394; p = 0.038, 0.001, and 0.009, respectively).
The present results suggest that genetic variants of the STK11, PRKAA1, and TSC1 genes could be used as prognostic biomarkers for patients with surgically resected colorectal cancer.
Annals of Surgical Oncology 04/2014; · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Robotic surgery is known to provide an improved technical ability as compared to laparoscopic surgery. We aimed to compare the efficiency of surgical skills by performing the same experimental tasks using both laparoscopic and robotic systems in an attempt to determine if a robotic system has an advantage over laparoscopic system.
[Show abstract][Hide abstract] ABSTRACT: The plant immune system needs to be tightly controlled both positively and negatively to maintain normal plant growth and health. We previously identified SUPPRESSOR OF rps4-RLD1 (SRFR1) as a negative regulator specifically of effector-triggered immunity. SRFR1 is localized in both a cytoplasmic microsomal compartment and in the nucleus. Its TPR domain has sequence similarity to TPR domains of transcriptional repressors in other organisms, suggesting that SRFR1 may negatively regulate effector-triggered immunity via transcriptional control. We show here that excluding SRFR1 from the nucleus prevented complementation of the srfr1 phenotype. To identify transcription factors that may interact with SRFR1, we screened by yeast two-hybrid assay an Arabidopsis transcription factor prey library and isolated six class I members of the TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factor family. Specific interactions were verified in planta. While single or double T-DNA mutant tcp8, tcp14 or tcp15 lines were not more susceptible to bacteria expressing AvrRps4, the triple tcp8 tcp14 tcp15 mutant displayed decreased effector-triggered immunity mediated by the resistance genes RPS4, RPS6, RPM1 and RPS2. In addition, expression of PATHOGENESIS-RELATED PROTEIN2 was attenuated in srfr1-4 tcp8-1 tcp14-5 tcp15-3 plants compared to srfr1-4. TCP transcription factors to date have been implicated largely in developmental processes. Our data indicate that one function of a subset of TCP proteins is to regulate defense gene expression in antagonism to SRFR1, and suggest a mechanism for an intimate connection between plant development and immunity. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Mutations in the inverted formin-2 (INF2) gene were recently identified in patients with autosomal dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) and focal segmental glomerulosclerosis (FSGS). Here, we identified a novel p.L132P INF2 mutation in a Korean family with DI-CMT and FSGS by whole exome sequencing. This mutation was cosegregated with affected individuals in the family and was not found in the 300 controls. The two affected members exhibited juvenile onset sensorimotor polyneuropathy and FSGS. Nerve conduction studies showed an intermediate range of motor nerve conduction velocities. We report a novel INF2 mutation in a family with DI-CMT and FSGS as the first case in Koreans. The INF2 mutation appears to be a major cause of CMT with FSGS.
Journal of the Peripheral Nervous System 04/2014; · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because predicting recurrence intervals and patterns would allow for appropriate therapeutic strategies, we evaluated the clinical and pathological characteristics of early and late recurrences of colorectal cancer.
Patients who developed recurrence after undergoing curative resection for colorectal cancer stage I-III between January 2000 and May 2006 were identified. Early recurrence was defined as recurrence within 2 years after primary surgery of colorectal cancer. Analyses were performed to compare the clinicopathological characteristics and overall survival rate between the early and late recurrence groups.
One hundred fifty-eight patients experienced early recurrence and 64 had late recurrence. Multivariate analysis revealed that the postoperative elevation of carbohydrate antigen 19-9 (CA 19-9), venous invasion, and N stage correlated with the recurrence interval. The liver was the most common site of early recurrence (40.5%), whereas late recurrence was more common locally (28.1%), or in the lung (32.8%). The 5-year overall survival rates for early and late recurrence were significantly different (34.7% vs. 78.8%; P < 0.001). Survival rates after the surgical resection of recurrent lesions were not different between the two groups.
Early recurrence within 2 years after surgery was associated with poor survival outcomes after colorectal cancer recurrence. An elevated postoperative CA 19-9 level, venous invasion, and advanced N stage were found to be significant risk factors for early recurrence of colorectal cancer.
Annals of surgical treatment and research. 03/2014; 86(3):143-51.
[Show abstract][Hide abstract] ABSTRACT: Although the vagina is considered a viable route during laparoscopic surgery, a number of concerns have led to a need to demonstrate the safety of a transvaginal approach in colorectal surgery. However, the data for transvaginal access in left-sided colorectal cancer are extremely limited, and no study has compared the clinical outcomes with a conventional laparoscopic procedure.
We compared the clinical outcomes of totally laparoscopic anterior resection with transvaginal specimen extraction (TVSE) with those of the conventional laparoscopic approach with minilaparotomy (LAP) for anastomosis construction and specimen retrieval in left-sided colorectal cancer.
Fifty-eight patients underwent TVSE between October 2006 and July 2011 and were matched by age, surgery date, tumor location, and tumor stage with patients who underwent conventional LAP for left-sided colorectal cancer.
Operative time was significantly longer in the TVSE group (149.3 ± 39.8 vs. 131.9 ± 41.4 min; p = 0.023). Patients in the TVSE group experienced less pain (pain score 4.9 ± 1.6 vs. 5.8 ± 1.9; p = 0.008), shorter time to passage of flatus (2.2 ± 1.1 vs. 2.7 ± 1.2 days; p = 0.026), and higher satisfaction with the cosmetic results (cosmetic score 8.0 ± 1.4 vs. 6.3 ± 1.5; p = 0.001). More endolinear staplers for rectal transection were used in the LAP group (1.2 ± 0.5 vs. 1.1 ± 0.2; p = 0.021). Overall morbidities were similar in both groups; however, three wound infections only occurred in the LAP group. After a median follow-up of 34.4 (range 11-60) months, no transvaginal access-site recurrence occurred. The 3-year disease-free survival was similar between groups (91.5 vs. 90.8 %; p = 0.746).
Transvaginal access after totally laparoscopic anterior resection is safe and feasible for left-sided colorectal cancer in selected patients with better short-term outcomes.
[Show abstract][Hide abstract] ABSTRACT: The extracapsular spread (ECS) of lymph node metastasis (LNM) reflects tumor aggressiveness and is associated with poor survival and risk of distant metastasis. In this study, we aimed to explore the prognostic significance of epithelial-mesenchymal transition (EMT) of ECS tumors in LNM of head and neck cancers.
We collected LNM samples from head and neck cancer patients (follow-up >2 years) and made 20 ECS(-): ECS(+) pairs (1:2) of LNM (N = 60), matched by the primary sites and by T and N classifications. Immunostaining of cytokeratin, E-cadherin, vimentin, and CD31 were performed and quantified to determine the epithelial-mesenchymal transition percent (EMT%), defined as vimentin(+)/cytokeratin(+) area of ECS. Univariate and multivariable analyses of clinic-pathologic factors, including EMT% of ECS, were conducted to identify the significant prognosticators. In addition, the anatomical relationship between CD31 vessels and ECS tumors was analyzed.
Rather than the presence of ECS in LNM, higher EMT% (>50 %) of ECS strongly correlated with the worse overall and disease-free survival and had more frequent recurrence and distant dissemination in their clinical courses. ECS tumors intermingled closely with Ki-67(-) CD31(+) non-proliferating perinodal blood vessels. Particularly, vimentin(+) ECS areas exhibited a higher density of CD31(+) perinodal vessels than did vimentin(-) ECS.
High EMT scores of ECS tumors in LNM predict an unfavorable prognosis and systemic dissemination more accurately than the simple presence of ECS in LNM in head and neck cancer patients.
Annals of Surgical Oncology 02/2014; · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies conducted cell expansion ex vivo using low initial plating densities for optimal expansion and subsequent differentiation of mesenchymal stem cells (MSCs). However, MSC populations are heterogeneous and culture conditions can affect the characteristics of MSCs. In this study, differences in gene expression profiles of adipose tissue (AT)-derived MSCs were examined after harvesting cells cultured at different densities. AT-MSCs from three different donors were plated at a density of 200 or 5,000 cells/cm(2). After 7 days in culture, detailed gene expression profiles were investigated using a DNA chip microarray, and subsequently validated using a reverse transcription polymerase chain reaction (RT-PCR) analysis. Gene expression profiles were influenced primarily by the level of cell confluence at harvest. In MSCs harvested at ∼90% confluence, 177 genes were up-regulated and 102 genes down-regulated relative to cells harvested at ∼50% confluence (P<0.05, FC>2). Proliferation-related genes were highly expressed in MSCs harvested at low density, while genes that were highly expressed in MSCs harvested at high density (∼90% confluent) were linked to immunity and defense, cell communication, signal transduction and cell motility. Several cytokine, chemokine and growth factor genes involved in immunosuppression, migration, and reconstitution of damaged tissues were up-regulated in MSCs harvested at high density compared with MSCs harvested at low density. These results imply that cell density at harvest is a critical factor for modulating the specific gene-expression patterns of heterogeneous MSCs.
PLoS ONE 01/2014; 9(1):e83363. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Distal myopathy with rimmed vacuoles (DMRV) or hereditary inclusion body myopathy 2 is an autosomal recessive muscular disorder characterized by early adult-onset weakness of distal muscles and rimmed vacuoles in muscle biopsy. Mutations in the UDP-N-acetylglucosamine 2-epimerase/N-ace-tylmannosamine kinase (GNE) gene are associated with the development of DMRV. In this study, whole exome sequencing (WES) revealed compound heterozygous GNE mutations of p.Asp176Val and p.Val572Leu in a patient with distal limb weakness. Three hundred healthy controls did not show these mutations. All other variants found in distal myopathy-relevant genes were polymorphic. These findings confirmed that the patient had DMRV. This work underscores the usefulness of WES in improving the molecular diagnosis of myopathy.
[Show abstract][Hide abstract] ABSTRACT: Few studies that meticulously match individual lymph nodes seen on MRI with their precise histologic counterparts after total mesorectal excision have been reported.
The objective of this study was to determine whether preoperative MRI could detect lymph node metastases accurately in the node-by-node analysis.
This was a prospective, observational cohort study.
The study was conducted at a tertiary-care hospital.
Forty patients with rectal cancer were enrolled.
Specimens were assessed using MRI for clinical staging. After surgical resection of the tumor, the specimens were again imaged with ex vivo ultrasound scan to localize the perirectal node. The locations of each lymph node were precisely matched with its corresponding magnetic resonance image to enable a node-for-node comparison of magnetic resonance images and histologic findings.
Agreement between MRI and histologic assessment of T stage was 82.5%. Of the 341 nodes harvested, 120 were too small (<3 mm) to be depicted on magnetic resonance images, and 18 of these contained metastasis (15%). A correlation between the results of MRI and histopathology was feasible for 205 lymph nodes, and the overall success rate of matching between the 2 techniques was 91.1% (205 of 221). Preoperative MRI revealed a node-by-node sensitivity and positive predictive value of 58.0%, and 61.7%. There was no difference in the diagnostic accuracy between the primary surgery subgroup and preoperative radiation subgroups.
The study is limited by its heterogeneity of cohorts including the subgroup with preoperative chemoradiation and the lack of preoperative ultrasound assessment.
Preoperative MRI was moderately accurate for the prediction of mesorectal lymph node metastasis. Moreover, preoperative MRI was insufficient for detecting small lymph nodes (<3 mm) with metastasis.
Diseases of the Colon & Rectum 01/2014; 57(1):32-8. · 3.20 Impact Factor