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1.  Dengue transmission model by means of viremic adult immuno-competent mouse 
Parasites & Vectors  2014;7:143.
Dengue virus infection manifests in three distinct forms in humans: dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Infection with the virus is a fatal disease; no vaccine is available and prevention depends on interruption of the chain of transmission. The study of dengue viral transmission by mosquitoes is hindered due to the lack of an affordable animal model. In general, immuno-competent mice are used as a simple and inexpensive animal model, but mice are not susceptible to dengue virus infection and therefore viremia will not occur following the inoculation of the virus in such mice. Here, we report a method for creating artificial viremia in immuno-competent mice, and further demonstrate the use of viremic mice to simultaneously infect a large number of Aedes aegypti.
We infected K562 cells with DENV-2 in the presence of an antibody against DENV-4. We then incubated the cells for 2 d before injecting the infected cells into C3H mice. After 5 h incubation, we allowed 100–150 female Aedes aegypti to feed on blood from the mice directly. We collected blood samples from the mice and from randomly selected Ae. aegypti at 2, 6, 12, and 24 h post-blood meal and screened the samples for DENV-2 genome as well as for virus concentration.
Our procedure provided high virus concentrations in the mice for at least 7 h after viral inoculation. We found that 13 out of 14 randomly picked mosquitoes were infected with DENV-2. High concentrations of virus were detected in the mosquitoes until at least 12 h post-infection.
Using the viremic immuno-competent mouse, we show that mass infection of Ae. aegypti is achievable. Compared to other infection techniques using direct inoculation, membrane-feeding, or immuno-deficient/humanized mice, we are confident that this method will provide a simpler and more efficient infection technique.
PMCID: PMC3976050  PMID: 24685121
Aedes aegypti; Dengue virus type 2; Mass-infection; Viremia; Immuno-competent mouse
2.  The Expression Profile of Phosphatidylinositol in High Spatial Resolution Imaging Mass Spectrometry as a Potential Biomarker for Prostate Cancer 
PLoS ONE  2014;9(2):e90242.
High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500–1000 was performed on optimal cutting temperature (OCT) compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS) showed that these molecules included 14 phosphatidylinositols (PIs), 3 phosphatidylethanolamines (PEs) and 3 phosphatidic acids (PAs). Among the PIs, the expression of PI(18:0/18:1), PI(18:0/20:3) and PI(18:0/20:2) were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA). The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.
PMCID: PMC3938652  PMID: 24587297
3.  Is Early Enteral Nutrition Initiated Within 24 Hours Better for the Postoperative Course in Esophageal Cancer Surgery? 
Early enteral nutrition within 24 h after surgery has become a recommended procedure. In the present study, we retrospectively examined whether initiating EN within 24 h after esophagectomy improves the postoperative course.
Among 103 patients who underwent thoracic esophagectomy for esophageal cancer, we enrolled the cases in which EN was initiated within 72 h after surgery. The patients were divided into two groups: EN started within 24 h (Group D1) and EN started at 24 - 72 h (Group D2-3). Clinical factors including days for first fecal passage, dose of postoperative albumin infusion, difference in serum albumin between pre- and postoperation, incidence of postoperative infection, and use of total parenteral nutrition were compared. Statistical analyses were performed by the Mann-Whitney U test and Chi square test, with significance defined as P < 0.05.
There was no significant difference between the groups in clinical factors. While pneumonia was significantly more frequent in Group D1 than in Group D2-3 (P = 0.0308), the frequency of infectious complications was comparable between the groups.
Initiating EN within 24 h showed no advantage for the postoperative course in esophageal cancer, and thus EN should be scheduled within 24 - 72 h, based on the patient condition.
PMCID: PMC3881990  PMID: 24400032
Early enteral nutrition; Esophageal cancer; Infectious complication; Pneumonia
4.  The diaphragms of fenestrated endothelia – gatekeepers of vascular permeability and blood composition 
Developmental cell  2012;23(6):1203-1218.
Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries causing a major leak of plasma proteins. This disruption results in early death of animals due to severe non-inflammatory protein loosing enteropathy. Deletion of PV1 in endothelium, but not the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.
PMCID: PMC3525343  PMID: 23237953
5.  Anaplastic Carcinoma of the Pancreas Mimicking Submucosal Gastric Tumor: A Case Report of a Rare Tumor 
Case Reports in Medicine  2013;2013:523237.
Anaplastic carcinoma of the pancreas (ACP) is a rare neoplasm of the pancreas. ACPs are aggressive neoplasms with a poorer prognosis than poorly differentiated ductal adenocarcinomas of the pancreas. The 3-year survival rate of patients with ACP is less than 3%, with a life expectancy of 10 to 20 months. We describe here a 64-year-old man with ACP mimicking a submucosal gastric tumor. The patient was found to have a giant mass mimicking a submucosal tumor. Total gastrectomy with splenectomy and partial resection of the tail of the pancreas were performed. The pathological diagnosis was ACP, with immunohistological findings showing pleomorphic-type ACP. Because the surgery was noncurative, the patient received adjuvant chemotherapy with paclitaxel but died of peritoneal dissemination and multiple liver metastases 4 months after surgery.
PMCID: PMC3870639  PMID: 24382965
6.  B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer 
Cancer research  2012;72(18):4765-4776.
Both the PI3K→Akt→mTOR and MAPK signaling pathways are often deregulated in prostate tumors with poor prognosis. Here we describe a new genetically-engineered mouse model of prostate cancer in which PI3K-Akt-mTOR signaling is activated by inducible disruption of PTEN, and ERK1/2 MAP kinase signaling is activated by inducible expression of a BRAFV600E oncogene. These tissue-specific compound mutant mice develop lethal prostate tumors that are inherently resistant to castration. These tumors bypass cellular senescence and disseminate to lymph nodes, bone marrow and lungs where they form overt metastases in ~30% of the cases. Activation of PI3K→Akt→mTOR and MAPK signaling pathways in these prostate tumors cooperate to upregulate c-Myc. Accordingly, therapeutic treatments with Rapamycin and PD0325901 to target these pathways, respectively, attenuate c-Myc levels and reduce tumor and metastatic burden. Together, our findings suggest a generalized therapeutic approach to target c-Myc activation in prostate cancer by combinatorial targeting of the PI3K→Akt→mTOR and ERK1/2 MAPK signaling pathways.
PMCID: PMC3445712  PMID: 22836754
Akt/mTOR signaling; MAP kinase signaling; genetically engineered mouse models; Braf; Myc
7.  TRAF6 Is Essential for Maintenance of Regulatory T Cells That Suppress Th2 Type Autoimmunity 
PLoS ONE  2013;8(9):e74639.
Regulatory T cells (Tregs) maintain immune homeostasis by limiting inflammatory responses. TRAF6 plays a key role in the regulation of innate and adaptive immunity by mediating signals from various receptors including the T-cell receptor (TCR). T cell-specific deletion of TRAF6 has been shown to induce multiorgan inflammatory disease, but the role of TRAF6 in Tregs remains to be investigated. Here, we generated Treg-specific TRAF6-deficient mice using Foxp3-Cre and TRAF6-flox mice. Treg-specific TRAF6-deficient (cKO) mice developed allergic skin diseases, arthritis, lymphadenopathy and hyper IgE phenotypes. Although TRAF6-deficient Tregs possess similar in vitro suppression activity compared to wild-type Tregs, TRAF6-deficient Tregs did not suppress colitis in lymphopenic mice very efficiently due to reduced number of Foxp3-positive cells. In addition, the fraction of TRAF6-deficient Tregs was reduced compared with wild-type Tregs in female cKO mice without inflammation. Moreover, adoptive transfer of Foxp3 + Tregs into Rag2-/- mice revealed that TRAF6-deficient Tregs converted into Foxp3- cells more rapidly than WT Tregs under lymphopenic conditions. Fate-mapping analysis also revealed that conversion of Tregs from Foxp3+ to Foxp3- (exFoxp3 cells) was accelerated in TRAF6-deficient Tregs. These data indicate that TRAF6 in Tregs plays important roles in the maintenance of Foxp3 in Tregs and in the suppression of pathogenic Th2 type conversion of Tregs.
PMCID: PMC3772853  PMID: 24058613
8.  Clinical Experience of Bronchoscopy-Guided Radiofrequency Ablation for Peripheral-Type Lung Cancer 
We have developed a new internal cooled electrode for radiofrequency ablation (RFA) (Japan Application no. 2006-88228) suitable for forceps channel bronchoscopy. Here, we present our clinical experience with bronchoscopy-guided RFA under computed tomography (CT) monitoring for patients with peripheral-type non-small-cell lung cancer (NSCLC). Bronchoscopy-guided RFA was performed in two patients (80 and 70 years old) with NSCLC, who had no lymph node involvement and distant metastases (T1N0M0), but not indicated for surgery because of other complications, such as advanced age, poor pulmonary function, and refusal of thoracic surgery. The locations of the tumors were right S2 and left S3, respectively. Although the tumors showed ground-glass opacity (GGO) with solid components in both cases, radiographic findings changed to reduced mass-like shadow and remained stable for 4 and 3.5 years after bronchoscopy-guided RFA. As the former case developed progressive disease on chest CT, bronchoscopy-guided RFA was repeated in the same lesion, resulting in no change for the subsequent 1 year. There were no adverse reactions during the procedures. Thus, bronchoscopy-guided RFA is a safe and feasible procedure that represents a potentially useful therapeutic tool in local control in medically inoperable patients with stage I NSCLC.
PMCID: PMC3784239  PMID: 24106625
9.  Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model 
Cancer research  2012;72(17):4483-4493.
While the prognosis for clinically localized prostate cancer is now favorable, there are still no curative treatments for castration-resistant prostate cancer and, therefore, remains fatal. In this study, we investigate a new therapeutic approach for treatment of castration-resistant prostate cancer, which involves dual targeting of a major signaling pathway that is frequently deregulated in the disease. We found that dual targeting of the Akt and mTOR signaling pathways with their respective inhibitors, MK-2206 and ridaforolimus (MK-8669), is highly effective for inhibiting castration-resistant prostate cancer in preclinical studies in vivo using a refined genetically-engineered mouse model of the disease. The efficacy of the combination treatment contrasts with their limited efficacy as single agents, since delivery of MK-2206 or MK-8669 individually had a modest impact in vivo on the overall tumor phenotype. In human prostate cancer cell lines, although not in the mouse model, the synergistic actions of MK-2206 and ridaforolimus (MK-8669) are due in part to limiting the mTORC2-feedback activation of Akt. Moreover, the effects of these drugs are mediated by inhibition of cellular proliferation via the retinoblastoma (RB) pathway. Our findings suggest that dual targeting the Akt and mTOR signaling pathways using MK-2206 and ridaforolimus (MK-8669) may be effective for treatment of castration-resistant prostate cancer, particularly for patients with deregulated RB pathway activity.
PMCID: PMC3432676  PMID: 22815528
Akt/mTOR signaling; castration-resistant prostate cancer; genetically engineered mouse models; preclinical analyses; Pten; RB
10.  Experimental Evidence of Persistent Androgen-Receptor-Dependency in Castration-Resistant Prostate Cancer 
In the majority of castration-resistant prostate cancer (CRPC), prostate-specific antigen (PSA), product of a gene that is almost exclusively regulated by the androgen receptor (AR), still acts as a serum marker reflecting disease burden, indicating that AR signaling is activated even under castrate level of serum androgen. Accumulated evidence shows that transcriptional ability of AR is activated both in ligand-dependent and -independent manners in CRPC cells. Some androgen-independent sublines derived from originally androgen-dependent LNCaP prostate cancer cells overexpress the AR and PSA, for which silencing the AR gene suppresses cellular proliferation. The overexpression of the AR confers androgen-independent growth ability on androgen-dependent prostate cancer cells. Some patient-derived prostate cancer xenograft lines also acquire castration-resistant growth ability secreting PSA. More recent publications have shown that the AR activated in CRPC cells regulates distinct gene sets from that in androgen-dependent status. This concept provides very important insights in the development of novel anti-prostate cancer drugs such as new generation anti-androgens and CYP17 inhibitors.
PMCID: PMC3759876  PMID: 23896594
prostate cancer; castration resistant; androgen receptor; molecular target
11.  Symptomatic cervical disc herniation in teenagers: two case reports 
The development of a symptomatic herniated cervical disc before the age of 20 is extremely rare. Sporadically reported cases of patients with cervical disc herniation under the age of 20 usually have had underlying disease.
Case presentation
Case 1: A 19-year-old Asian man visited our clinic and presented with progressive pain in his upper left scapula and weakness of the left deltoid and biceps brachii muscles. C5 radiculopathy by soft disc herniation at C4-C5 without calcification was diagnosed. Microsurgical posterior foraminotomy was performed and he recovered completely eight weeks after the surgery.
Case 2: A 15-year-old Asian man presented with difficulty in lifting his arm and neck pain on the right side. Neurological examination showed weakness of the right deltoid and biceps brachii muscles. A magnetic resonance imaging scan demonstrated a herniated intervertebral disc in the right C4-C5 foramen. The patient was treated conservatively and put under observation only, and had completely recovered eight weeks after admission.
Although extremely rare, symptomatic cervical disc herniations may occur even in the younger population under the age of 20 without any trauma or underlying disease. Favorable outcomes can be achieved by conventional treatments for cervical disc herniation.
PMCID: PMC3599747  PMID: 23402661
12.  Preclinical analyses of intravesical chemotherapy for prevention of bladder cancer progression 
Oncotarget  2013;4(2):269-276.
There is a critical need to identify treatment options for patients at high risk for developing muscle invasive bladder cancer that avoid surgical removal of the bladder (cystectomy). In the current study, we have performed preclinical studies to investigate the efficacy of intravesical delivery of chemotherapy for preventing progression of bladder cancer. We evaluated three chemotherapy agents, namely cisplatin, gemcitabine, and docetaxel, which are currently in use clinically for systemic treatment of muscle invasive bladder cancer and/or have been evaluated for intravesical therapy. These preclinical studies were done using a genetically-engineered mouse (GEM) model that progresses from carcinoma in situ (CIS) to invasive, metastatic bladder cancer. We performed intravesical treatment in this GEM model using cisplatin, gemcitabine, and/or docetaxel, alone or by combining two agents, and evaluated whether such treatments inhibited progression to invasive, metastatic bladder cancer. Of the three single agents tested, gemcitabine was most effective for preventing progression to invasive disease, as assessed by several relevant endpoints. However, the combinations of two agents, and particularly those including gemcitabine, were more effective for reducing both tumor and metastatic burden. Our findings suggest combination intravesical chemotherapy may provide a viable bladder-sparing treatment alternative for patients at high risk for developing invasive bladder cancer, which can be evaluated in appropriate clinical trials.
PMCID: PMC3712572  PMID: 23563166
Non-muscle invasive bladder cancer; intravesical therapy; genetically engineered mouse models; preclinical studies
13.  Promotion of the lipase-catalyzed hydrolysis of conjugated linoleic acid l-menthyl ester by addition of an organic solvent 
SpringerPlus  2012;1(1):67.
Conjugated linoleic acid l-menthyl ester was hydrolyzed in water by the lipase from Candida rugosa with the addition of an organic solvent. The degree of hydrolysis (yield) greatly improved when a tertiary alcohol, such as t-butyl alcohol, was added. However, the addition of a less polar solvent, such as hexane, decreased the degree of hydrolysis, and some water-miscible solvents, such as acetone, caused inactivation of the lipase. With the addition of t-butyl alcohol, the reaction mixture formed a one- or two-phase system, and the mixing ratio of substrates and t-butyl alcohol determined the number of phases. Although the degree of hydrolysis at 10 d was higher in the one-phase system, the initial reaction rate was generally lower. Meanwhile, the reaction was much faster in the two-phase system while maintaining a moderate degree of hydrolysis.
PMCID: PMC3568468  PMID: 23420098
Conjugated linoleic acid; Ester; Hydrolysis; Lipase; Organic solvent
14.  Acute myeloid leukemia with cryptic CBFB-MYH11 type D 
A 77 year-old female was found with FAB M4Eo acute myeloid leukemia. Although CBFB-MYH11 mRNA was detected in RT-PCR, the conventional cytogenetic analysis failed to reveal inv(16). Fluorescence in situ hybridization (FISH) and the sequence analysis revealed a fusion between the exon 5 of CBFB and the exon 8 of MYH11, resulting in a minor variant fusion product previously reported as type D. In order to detect the cryptic inv(16) type D, both FISH and RT-PCR are required, and furthermore, the primers for the sequence analysis needs to be selected for the proper diagnosis.
PMCID: PMC3515980  PMID: 23236551
Acute myeloid leukemia; inversion 16; CBFB-MYH11; RT-PCR; fluorescence in situ hybridization
15.  Overexpression of ETS-1 is associated with malignant biological features of prostate cancer 
Asian Journal of Andrology  2012;14(6):860-863.
E26 transformation-specific-1 (ETS-1), an ETS family transcription factor, has been reported to play an important role in a variety of physiological and pathological processes, but clinical implications of ETS-1 expression in prostate cancer (PCa), particularly high-risk cases, including response to androgen-deprivation therapy (ADT) have yet to be elucidated. We examined the expression of ETS-1 using immunohistochemical staining of paraffin-embedded prostate carcinoma tissue obtained by needle biopsy from 69 mostly advanced PCa patients. ETS-1 expression was compared with the clinicopathological characteristics of the 69 patients, including 25 who underwent ADT as a primary treatment. As a result, PCa patients with higher expression of ETS-1 were significantly more likely to be of high stage and high Gleason score (P<0.05). There was no significant association between ETS-1 expression and the initial prostate-specific antigen (PSA) level. In the 25 patients treated by ADT, the staining score for ETS-1 was significantly associated with rapid development of castration-resistant disease within 24 months (P<0.05), whereas the Gleason score and PSA level were not. In conclusion, increased ETS-1 expression was associated with a higher stage, higher Gleason score and shorter time to castration-resistant progression. These data suggest that immunostaining for ETS-1 could be a molecular marker for predicting a poor clinical outcome for PCa patients, particularly those with high-risk disease.
PMCID: PMC3720114  PMID: 23064684
castration resistant; E26 transformation-specific-1 (ETS-1); immunohistochemistry; prostate cancer
16.  2,6-Dimeth­oxy-9,10-anthraquinone 
The title compound, C16H12O4, crystallizes with two half-mol­ecules in the asymmetric unit, each of which is completed by a crystallographic inversion center. The two crystallographically independent mol­ecules have almost the same geometry and are almost planar [maximum deviations = 0.018 (3) and 0.049 (3) Å]. They adopt a conformation in which the Cmeth­yl—O bonds are directed along the mol­ecular short axis [C—C—O—C torsion angles of 179.6 (2) and 178.0 (2)°]. In the crystal, the mol­ecular packing is characterized by a combination of a columnar stacking and a herringbone-like arrangement. The mol­ecules form slipped π-stacks along the b axis, in which there are two kinds of columns differing from each other in their slippage. The inter­planar distances between neighboring mol­ecules are 3.493 (3) for one column and 3.451 (2) Å for the other.
PMCID: PMC3470203  PMID: 23125647
17.  2,3,6,7-Tetra­meth­oxy-9,10-anthra­quinone 
Mol­ecules of the title compound, C18H16O6, are almost planar [maximum deviation = 0.096 (4) Å] and reside on crystallographic centres of inversion. They adopt a conformation in which the Cmeth­yl—O bonds are directed along the mol­ecular short axis [C—C—O—C torsion angles of −175.3 (3) and 178.2 (3)°]. In the crystal, mol­ecules adopt a slipped-parallel arrangement with π–π stacking inter­actions along the a axis with an inter­planar distance of 3.392 (4) Å. Weak C—H⋯O inter­actions link the mol­ecules into sheets parallel to (10-2).
PMCID: PMC3415025  PMID: 22905012
18.  A Novel Serum Metabolomics-Based Diagnostic Approach for Colorectal Cancer 
PLoS ONE  2012;7(7):e40459.
To improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer.
Methodology/Principal Findings
We performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS). First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD% values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night) and inter-day (among 3 days) variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N = 60; N = 12 for each stage from 0 to 4) and age- and sex-matched healthy volunteers (N = 60) as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0%, 85.0%, and 85.0%, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0%, 96.7%, and 65.8%, respectively, and those of CA19-9 were 16.7%, 100%, and 58.3%, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N = 59) and healthy volunteers (N = 63) as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1%, 81.0%, and 82.0%, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0–2 colorectal cancer (82.8%).
Our prediction model established via GC/MS-based serum metabolomic analysis is valuable for early detection of colorectal cancer and has the potential to become a novel screening test for colorectal cancer.
PMCID: PMC3394708  PMID: 22792336
20.  Anterior Decompression and Shortening Reconstruction with a Titanium Mesh Cage through a Posterior Approach Alone for the Treatment of Lumbar Burst Fractures 
Asian Spine Journal  2012;6(2):123-130.
Study Design
A retrospective study.
To examine the efficacy and safety for a posterior-approach circumferential decompression and shortening reconstruction with a titanium mesh cage for lumbar burst fractures.
Overview of Literature
Surgical decompression and reconstruction for severely unstable lumbar burst fractures requires an anterior or combined anteroposterior approach. Furthermore, anterior instrumentation for the lower lumbar is restricted through the presence of major vessels.
Three patients with an L1 burst fracture, one with an L3 and three with an L4 (5 men, 2 women; mean age, 65.0 years) who underwent circumferential decompression and shortening reconstruction with a titanium mesh cage through a posterior approach alone and a 4-year follow-up were evaluated regarding the clinical and radiological course.
Mean operative time was 277 minutes. Mean blood loss was 471 ml. In 6 patients, the Frankel score improved more than one grade after surgery, and the remaining patient was at Frankel E both before and after surgery. Mean preoperative visual analogue scale was 7.0, improving to 0.7 postoperatively. Local kyphosis improved from 15.7° before surgery to -11.0° after surgery. In 3 cases regarding the mid to lower lumbar patients, local kyphosis increased more than 10° by 3 months following surgery, due to subsidence of the cages. One patient developed severe tilting and subsidence of the cage, requiring additional surgery.
The results concerning this small series suggest the feasibility, efficacy, and safety of this treatment for unstable lumbar burst fractures. This technique from a posterior approach alone offers several advantages over traditional anterior or combined anteroposterior approaches.
PMCID: PMC3372547  PMID: 22708016
Lumbar spine; Burst fracture; Posterior approach
21.  Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization 
The Journal of Experimental Medicine  2011;208(11):2175-2181.
The mobilization of hematopoietic stem cells does not require osteoclasts, which may even have an inhibitory effect.
Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.
PMCID: PMC3201203  PMID: 22006978
22.  Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study 
Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.
PMCID: PMC3296209  PMID: 22474446
23.  Development of Pancreatic Ductal Adenocarcinoma Associated with Intraductal Papillary Mucinous Neoplasia 
ISRN Gastroenterology  2011;2011:940378.
We retrospectively investigated the incidence of pancreatic ductal adenocarcinoma among patients with intraductal papillary mucinous neoplasms of the pancreas. Based on imaging in 195 such patients, we chose surgery as initial treatment for 54, and periodic evaluation over 6 to 192 months (mean, 52) for 141. In 6 of the 141 patients observed for intraductal papillary mucinous neoplasm (4.2%), pancreatic ductal adenocarcinoma developed. Further, careful monitoring for cancer occurrence in the remnant pancreas proved essential in the surgical resection group; 2 of 26 patients (7.7%) subsequently developed pancreatic ductal adenocarcinoma in the remnant pancreas, at 41 months and 137 months after surgery. Serial observation of patients with intraductal papillary mucinous neoplasms by contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography therefore is critical, whether or not surgical treatment initially was performed.
PMCID: PMC3235575  PMID: 22191040
24.  Public health information and statistics dissemination efforts for Indonesia on the Internet 
Online Journal of Public Health Informatics  2011;3(2):ojphi.v3i2.3602.
To elucidate current issues related to health statistics dissemination efforts on the Internet in Indonesia and to propose a new dissemination website as a solution.
A cross-sectional survey was conducted. Sources of statistics were identified using link relationship and Google™ search. Menu used to locate statistics, mode of presentation and means of access to statistics, and available statistics were assessed for each site. Assessment results were used to derive design specification; a prototype system was developed and evaluated with usability test.
49 sources were identified on 18 governmental, 8 international and 5 non-government websites. Of 49 menus identified, 33% used non-intuitive titles and lead to inefficient search. 69% of them were on government websites. Of 31 websites, only 39% and 23% used graph/chart and map for presentation. Further, only 32%, 39% and 19% provided query, export and print feature. While >50% sources reported morbidity, risk factor and service provision statistics, <40% sources reported health resource and mortality statistics. Statistics portal website was developed using Joomla!™ content management system. Usability test demonstrated its potential to improve data accessibility.
Discussion and conclusion:
In this study, government’s efforts to disseminate statistics in Indonesia are supported by non-governmental and international organizations and existing their information may not be very useful because it is: a) not widely distributed, b) difficult to locate, and c) not effectively communicated. Actions are needed to ensure information usability, and one of such actions is the development of statistics portal website.
PMCID: PMC3615789  PMID: 23569612
public health; public information; statistics; web services; usability
25.  1,7-Diethyl-4,10-diisopropyl­tetra­cene 
The mol­ecule of the title compound, C28H32, is located on a crystallographic inversion center. The ethyl groups are essentially coplanar with the tetra­cene ring, making a torsion angle of −0.4 (4)°. The isopropyl groups adopt an asymmetric conformation with their terminal methyl groups positioned on opposite sides of the tetra­cene plane [the Me—C—C—C torsion angles are −22.5 (4) and 100.9 (3)°]. In the crystal, the mol­ecules adopt an arrangement without significant π–π inter­actions along the stacking direction (y axis).
PMCID: PMC3201380  PMID: 22058757

Results 1-25 (42)