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1.  Structure-Based Gene Targeting Discovery of a Novel Bacterial Translocase I Inhibitor, Sphaerimicin** 
Angewandte Chemie (International ed. in English)  2013;52(44):10.1002/anie.201305546.
PMCID: PMC3873198  PMID: 24014169
Bacterial translocase I inhibitor; Nucleoside Antibiotics; Transaldolase; Gene-Targeting Approach; Actinomycetes
2.  Embolization of a fractured central venous catheter placed using the internal jugular approach 
Fracture and embolization of central venous catheters placed via the subclavian approach is well recognized, but fractured catheters placed via the internal jugular vein are extremely rare.
A 65-year-old man presented with a catheter embolus after placement of a central venous port using the internal jugular approach undertaken to administer adjuvant chemotherapy for colon cancer with lung metastases. Goose neck and conformational loop snares were successfully used to percutaneously retrieve the severed catheter, which had migrated to the right ventricle.
Catheter fracture may occur even after placement via the internal jugular approach and may be underestimated because it is often asymptomatic. Interventional radiology techniques using goose-neck and conformational loop snares may be useful to retract an intravascular foreign body.
Imaging studies such as a chest X-ray are mandatory to check that the catheter tip is in the appropriate position during the entire follow-up period even if it was placed through the internal jugular vein.
PMCID: PMC4008853  PMID: 24705188
Central venous catheter; Catheter embolus; Internal jugular vein; Interventional radiology
3.  Effect of Cryopreservation on Canine and Human Activated Nucleus Pulposus Cells: A Feasibility Study for Cell Therapy of the Intervertebral Disc 
BioResearch Open Access  2013;2(4):273-282.
It has been shown that coculture of bone marrow–derived stromal cells (BMSCs) with intervertebral disc (IVD) nucleus pulposus (NP) cells significantly activates the biological characteristics of NP cells in animal models and in humans. We therefore predicted that activated NP cells would be a useful graft source for cellular transplantation therapy in the treatment of degenerative IVDs. However, the activation protocol is based on fresh isolation and activation of NP cells, which limits the timing of clinical application. Cell transplantation therapy could be offered to more patients than is now possible if activated NP cells could be transplanted as and when required by the condition of the patient. No study has investigated the effect of cryopreservation on NP cells after enzymatic isolation. We investigated the effects of cryopreservation of canine and human NP cells in both cell and tissue form before coculture with autologous BMSCs. Cell viability, proliferation, glycosaminoglycan production, aggrecan transcriptional activity, colony generation, and gene expression profile of the cells after cryopreservation and subsequent coculture were analyzed. The influence of cryopreservation on cell chromosomal abnormalities and tumorigenesis was also studied. The results showed that there were no clear differences between the noncryopreserved and cryopreserved cells in terms of cell viability, proliferation capacity, and capacity to synthesize extracellular matrix. Furthermore, the cells showed no apparent chromosomal abnormalities or tumorigenic ability and exhibited similar patterns of gene expression. These findings suggest that by using cryopreservation, it may be possible to transplant activated NP cells upon request for patients' needs.
PMCID: PMC3731681  PMID: 23914334
cryopreservation; intervertebral disc; nucleus pulposus; stem cells
4.  Enhancement of Intervertebral Disc Cell Senescence by WNT/β-Catenin Signaling–Induced Matrix Metalloproteinase Expression 
Arthritis and rheumatism  2010;62(10):3036-3047.
To determine whether intervertebral disc (IVD) cells express β-catenin and to assess the role of the WNT/β-catenin signaling pathway in cellular senescence and aggrecan synthesis.
The expression of β-catenin messenger RNA (mRNA) and protein in rat IVD cells was assessed by using several real-time reverse transcription–polymerase chain reaction, Western blot, immunohistochemical, and immunofluorescence analyses. The effect of WNT/β-catenin on nucleus pulposus (NP) cells was examined by transfection experiments, an MTT assay, senescence-associated β-galactosidase staining, a cell cycle analysis, and a transforming growth factor (TGFβ)/bone morphogenetic protein (BMP) pathway–focused microarray analysis.
We found that β-catenin mRNA and protein were expressed in discs in vivo and that rat NP cells exhibited increased β-catenin mRNA and protein upon stimulation with lithium chloride, a known activator of WNT signaling. LiCl treatment inhibited the proliferation of NP cells in a time- and dose-dependent manner. In addition, there was an increased level of cellular senescence in LiCl-treated cells. Long-term treatment with LiCl induced cell cycle arrest and promoted subsequent apoptosis in NP cells. Activation of WNT/β-catenin signaling also regulated the expression of aggrecan. We also demonstrated that WNT/β-catenin signaling induced the expression of matrix metalloproteinases (MMPs) and TGFβ in NP cells.
The activation of WNT/β-catenin signaling promotes cellular senescence and may modulate MMP and TGFβ signaling in NP cells. We hypothesize that the activation of WNT/β-catenin signaling may lead to an increased breakdown of the matrix, thereby promoting IVD degeneration.
PMCID: PMC3622204  PMID: 20533544
5.  Relationship between Cariogenic Bacteria and pH of Dental Plaque at Margin of Fixed Prostheses 
Objective. The purpose of this study was to investigate whether teeth that have undergone prosthetic restoration are under conditions that promote caries recurrence. Methods. The subjects were 20 dentate adults with both a healthy tooth and an affected tooth entirely covered with a complete cast crown in the molar regions of the same arch. The pH was measured in plaque adhering to the margin of the tooth covered with a complete cast crown and adhering to the cervicobuccal area of the natural tooth. In addition, the numbers of cariogenic bacteria (mutans streptococci and lactobacilli) were measured employing the saliva test. The relationships between the number of cariogenic bacteria and plaque pH of the natural tooth and between the number of cariogenic bacteria and plaque pH of the tooth covered with a complete cast crown were investigated. Results. The plaque pH of the tooth covered with a complete cast crown decreased as the numbers of SM and LB increased. The natural tooth were also influenced by the number of SM. Conclusion. Secondary caries are likely to develop from the marginal region of the crown in the oral cavity with a high caries risk unless a preventive program is prepared and the oral environment is improved following the program.
PMCID: PMC3263602  PMID: 22287964
6.  Hepatitis B and C Virus Infection and Hepatocellular Carcinoma in China: A Review of Epidemiology and Control Measures 
Journal of Epidemiology  2011;21(6):401-416.
China has one of the highest carrier prevalences of hepatitis B virus (HBV) in the world: nearly 10% of the general population. The disease burden of HBV infection and hepatocellular carcinoma (HCC) is also believed to be among the world’s largest, and that of hepatitis C virus (HCV) infection is likely to be substantial as well. However, the epidemiology and measures to control HBV and HCV infection in China remain relatively unknown outside the country. We review the epidemiology of HBV and HCV infection, the disease burden of and risk factors for HCC, and current control measures against HBV and HCV infection in China. We also discuss the relevant literature and implications for future studies of hepatitis and HCC in China.
PMCID: PMC3899457  PMID: 22041528
China; hepatitis; hepatocellular carcinoma; epidemiology; control
7.  Agile parallel bioinformatics workflow management using Pwrake 
BMC Research Notes  2011;4:331.
In bioinformatics projects, scientific workflow systems are widely used to manage computational procedures. Full-featured workflow systems have been proposed to fulfil the demand for workflow management. However, such systems tend to be over-weighted for actual bioinformatics practices. We realize that quick deployment of cutting-edge software implementing advanced algorithms and data formats, and continuous adaptation to changes in computational resources and the environment are often prioritized in scientific workflow management. These features have a greater affinity with the agile software development method through iterative development phases after trial and error.
Here, we show the application of a scientific workflow system Pwrake to bioinformatics workflows. Pwrake is a parallel workflow extension of Ruby's standard build tool Rake, the flexibility of which has been demonstrated in the astronomy domain. Therefore, we hypothesize that Pwrake also has advantages in actual bioinformatics workflows.
We implemented the Pwrake workflows to process next generation sequencing data using the Genomic Analysis Toolkit (GATK) and Dindel. GATK and Dindel workflows are typical examples of sequential and parallel workflows, respectively. We found that in practice, actual scientific workflow development iterates over two phases, the workflow definition phase and the parameter adjustment phase. We introduced separate workflow definitions to help focus on each of the two developmental phases, as well as helper methods to simplify the descriptions. This approach increased iterative development efficiency. Moreover, we implemented combined workflows to demonstrate modularity of the GATK and Dindel workflows.
Pwrake enables agile management of scientific workflows in the bioinformatics domain. The internal domain specific language design built on Ruby gives the flexibility of rakefiles for writing scientific workflows. Furthermore, readability and maintainability of rakefiles may facilitate sharing workflows among the scientific community. Workflows for GATK and Dindel are available at
PMCID: PMC3180464  PMID: 21899774
8.  Clinical significance of subepithelial growth patterns in non-muscle invasive bladder cancer 
BMC Urology  2011;11:17.
We evaluated the clinical significance and prognostic value of histopathological features of bladder cancer, such as subepithelial growth patterns and tumor growth pattern at the invasion front.
In total, 130 patients newly diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection between 1998 and 2009 were enrolled. Subepithelial growth patterns consisting of endophytic growth pattern (EGP) and von Brunn's nest involvement (VBNI) were investigated using hematoxylin and eosin-stained slides, and their frequency of occurrence, prognostic value, and correlation with other clinicopathological features was evaluated.
EGP and VBNI were found in 40 (30.8%) and 5 (3.9%) of the 130 cases, respectively. Of the 26 pT1 tumors, the growth pattern at the invasion front was trabecular in 17 (65.4%) and infiltrative in 9 (34.6%). Although 8 (47.1%) of 17 trabecular tumors coexisted with EGP, no cases with infiltrative tumors had EGP (p = 0.023). VBNI correlated with high tumor grades (p = 0.006) and lymphovascular involvement (p = 0.026). The multivariate Cox proportional hazards analysis revealed that tumor diameter less than 3 cm (p = 0.04) and intravesical bacillus Calmette-Guérin therapy (p = 0.004) were independent favorable prognostic factors for recurrence-free survival, whereas tumor stage was an independent poor prognostic factor for disease progression (p = 0.006).
Subepithelial growth patterns were not a significant prognostic factor in this study. Additionally, no tumors with an infiltrative growth pattern coexisted with EGP, suggesting that determining the presence of EGP might be helpful for managing non-muscle invasive bladder cancers.
PMCID: PMC3167754  PMID: 21816111
bladder cancer; endophytic growth pattern; prognostic factor; infiltrative pattern
9.  Influence of Type of Prosthesis on Oral Environment and the Number of Missing Teeth in Elderly Persons 
The purpose of this study was to investigate the relationship between the number of missing teeth (MT) and the statuses of oral environmental factors (the stimulated salivary flow rate, buffering capacity, and the counts of mutans streptococci, lactobacilli, and Candida) in the elderly. The subjects were 64 elderly subjects with fixed prostheses and 49 who wore removable partial dentures aged over 65 years. We used one-way ANOVA to test for overall differences of the number of MT among 5 oral environmental factors. The significant differences were observed in the lactobacilli counts for different number of MT. The number of MT increased with an increase in the lactobacilli counts with removable denture. In conclusion, for the patients wearing removable dentures, increasing number of MT was associated with an increase in the lactobacilli counts in saliva. For the patients with crowns and fixed partial dentures, the number of MT was not significantly affected by salivary mutans streptococci, lactobacilli, and Candida counts.
PMCID: PMC2945642  PMID: 20886059
10.  An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules 
PLoS Biology  2005;3(5):e128.
We have implemented an unbiased cell morphology–based screen to identify small-molecule modulators of cellular processes using the Cytometrix (TM) automated imaging and analysis system. This assay format provides unbiased analysis of morphological effects induced by small molecules by capturing phenotypic readouts of most known classes of pharmacological agents and has the potential to read out pathways for which little is known. Four human-cancer cell lines and one noncancerous primary cell type were treated with 107 small molecules comprising four different protein kinase–inhibitor scaffolds. Cellular phenotypes induced by each compound were quantified by multivariate statistical analysis of the morphology, staining intensity, and spatial attributes of the cellular nuclei, microtubules, and Golgi compartments. Principal component analysis was used to identify inhibitors of cellular components not targeted by known protein kinase inhibitors. Here we focus on a hydroxyl-substituted analog (hydroxy-PP) of the known Src-family kinase inhibitor PP2 because it induced cell-specific morphological features distinct from all known kinase inhibitors in the collection. We used affinity purification to identify a target of hydroxy-PP, carbonyl reductase 1 (CBR1), a short-chain dehydrogenase-reductase. We solved the X-ray crystal structure of the CBR1/hydroxy-PP complex to 1.24 Å resolution. Structure-based design of more potent and selective CBR1 inhibitors provided probes for analyzing the biological function of CBR1 in A549 cells. These studies revealed a previously unknown function for CBR1 in serum-withdrawal-induced apoptosis. Further studies indicate CBR1 inhibitors may enhance the effectiveness of anticancer anthracyclines. Morphology-based screening of diverse cancer cell types has provided a method for discovering potent new small-molecule probes for cell biological studies and anticancer drug candidates.
An imaging-based screen, followed by structural and functional analysis, led to the discovery of new inhibitors of carbonyl reductase 1, a potential anticancer target
PMCID: PMC1073692  PMID: 15799708

Results 1-10 (10)