[Show abstract][Hide abstract] ABSTRACT: Interleukin (IL)-32 has been associated with a variety of inflammatory diseases including rheumatoid arthritis, vasculitis and Crohn's disease. We have previously reported that IL-32γ, the IL-32 isoform with the highest biological activity, could act as an immune modulator through regulation of dendritic cell (DC) functions in immune responses. Cell locomotion is crucial for induction of an effective immune response. In this study, we investigated the effect and underlying mechanisms of IL-32γ on recruitment of T cells. IL-32γ upregulated the expression of several chemokines including CCL2, CCL4, and CCL5 in the DCs. In particular, IL-32γ significantly increased CCL5 expression in a dose-dependent manner. Treatment with JNK and NF-κB inhibitors suppressed IL-32γ-induced CCL5 expression in DCs, indicating that IL-32γ induced CCL5 production through the JNK and NF-κB pathways. Furthermore, supernatants from IL-32γ-treated DCs showed chemotactic activities controlling migration of activated CD4(+) and CD8(+) T cells, and these activities were suppressed by addition of neutralizing anti-CCL5 antibody. These results show that IL-32γ effectively promotes migration of activated T cells via CCL5 production in DCs. The chemotactic potential of IL-32γ may explain the pro-inflammatory effects of IL-32 and the pathologic role of IL-32 in immune disorders such as rheumatoid arthritis.
Biochemical and Biophysical Research Communications 05/2014; · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transcriptomes from high-throughput sequencing technology provide a good resource for molecular markers. Here, we report the development of polymorphic simple sequence repeat (SSR) markers from transcript sequences via 454 pyrosequencing for Vicia sativa subsp. nigra (narrow-leaved vetch). In contrast to V. sativa subsp. sativa, the most commonly grown vetch species, the narrow-leaved vetch survives in diverse soil and climate conditions, serving as a valuable breeding resource of environmental tolerance. We found 2,429 SSR loci from 17,971 individual sequence reads, and 100 primer pairs were designed and synthesized. In total, 49 primer pairs were polymorphic when screened in 32 accessions. The number of alleles was 2–19, the frequency of major alleles per locus varied from 0.19 to 0.87, the genotype numbers ranged from 2 to 19, and observed and expected heterozygosity values ranged from 0.00 to 0.78 and from 0.23 to 0.92, respectively. Polymorphism index content values ranged from 0.20 to 0.86. Considering the relatively high polymorphism in the selected cDNA-SSR marker sets, these markers can be applied to assess genetic diversity, population structure, and positional cloning for the narrow-leaved vetch to facilitate vetch breeding programs.
[Show abstract][Hide abstract] ABSTRACT: Interleukin-32 (IL-32) is a cytokine produced by T lymphocytes, natural killer (NK) cells, monocytes and epithelial cells. There are five splicing variants (α, β, γ, δ, and ε) and IL-32γ is the most active isoform. We generated human IL-32γ transgenic (IL-32γ TG) mice, displaying a high level of IL-32γ expression in the pancreas. We investigated the effect of IL-32γ on streptozotocin (STZ)-induced type 1 diabetes model using IL-32γ TG mice. After a suboptimal diabetogenic dose of STZ administration, IL-32γ TG mice showed significantly increased blood glucose level comparing with that of wild type (WT) mice at day 5. Inflammatory cytokines levels such as, IL-6, TNFα, IFNγ and IL-1β, in pancreas and liver lysates were accessed by a specific cytokine ELISA. The proinflammatory cytokines were significantly enhanced in the pancreas of IL-32γ TG mice comparing to that of WT mice whereas those cytokines levels in liver of IL-32γ TG and WT mice were not changed by STZ. These data indicate that the overexpression of IL-32γ contributes to initial islet β-cells injury and inflammation in pancreas and aggravates STZ-induced type 1 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Diffuse pulmonary lymphangiomatosis (DPL) is a rare lymphatic disorder characterized by lymphatic channel proliferation. It is mostly reported in children and young adults. Here, we report a case involving a 52-year-old asymptomatic woman who presented with increased interstitial markings, as seen on a chest radiograph. Diffuse interstitial septal thickening was found on a serial follow-up chest computed tomography scan, and lymphangitic metastasis was the primary radiologic differential diagnosis. However, histologic sections of wedge resected lung revealed diffuse pleural and interlobular septal lymphatic proliferation characteristic of DPL.
Korean journal of radiology: official journal of the Korean Radiological Society 01/2014; 15(2):295-299. · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: All-trans retinoic acid (ATRA) is one of the most useful drugs in the treatment for acute promyelocytic leukemia (APL), but its adverse effects, which include drug resistance and hypercalcemia are obstacles to achieving complete remission. Our previous study showed that some sesquiterpene lactones (STLs), i.e., helenalin (HE) and parthenolide (PA) but not sclareolide (SC), enhance ATRA-induced differentiation of HL-60 APL cells with no unexpected effects, but the precise mechanism on underlying this synergism is not yet fully understood. In this study, we investigated the distinctive transcriptional profile of cells treated with effective STL compounds, which were identified by comparing the profile with that of cells treated with SC. Genome-wide approaches using cDNA microarrays showed that co-treatment with the differentiation-enhancing STLs HE and PA maximized the transcriptional variation regulated by the suboptimal concentration of ATRA in HL-60 cells. Of the genes of interest, asparagine synthetase was remarkably downregulated by ATRA co-treated with either HE or PA, but not with SC. In an additional analysis for the role of asparagine synthetase, ATRA-mediated HL-60 cell differentiation was enhanced when asparagine in the culture media was depleted by an addition of L-asparaginase, indicating that downregulation of asparagine synthetase gene expression may be involved in the enhanced cell differentiation by STL compounds. These results provide useful insight into differentiation-inducing therapy in the treatment of leukemia.
International Journal of Oncology 12/2013; · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PET is a potentially useful modality for response analysis and prognosis prediction in patients with high-grade non-Hodgkin lymphoma (NHL). The thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was recently introduced as a new tracer. (18)F-FLT uptake correlates with tumor cell proliferation and is suggested to reflect early response to treatment. We performed a prospective study to evaluate the prognostic value of early interim (18)F-FLT PET in patients with NHL.
Patients with untreated NHL were enrolled between 2005 and 2007. Among them, 61 pairs of (18)F-FLT PET images were obtained at baseline (pre), after 1 cycle of chemotherapy (interim), and at the end of all scheduled first-line chemotherapy (final). All (18)F-FLT PET scans were interpreted by quantitative methods (maximum standardized uptake value [SUVmax] and mean standardized uptake value [SUVmean]). Receiver-operating-characteristic curve analysis was performed to define (18)F-FLT PET positivity using a cutoff value predicting disease progression, relapse, or death. Survival outcome was measured by progression-free survival (PFS) and overall survival (OS) rates.
Receiver-operating-characteristic curve analysis of SUVmax for prediction of disease progression and death showed the highest area under the curve (AUC) in interim (18)F-FLT PET scans (AUC of 0.841 for PFS and 0.834 for OS, with a cutoff of 1.86; P < 0.001), compared with pre and final (18)F-FLT PET scans. The SUVmean in interim (18)F-FLT PET scans also showed better prediction (AUC of 0.842 for PFS and 0.824 for OS, with a cutoff value of 1.65; P < 0.001) than pre and final (18)F-FLT PET scans. Patients with an interim (18)F-FLT PET SUVmax more than 1.86, who were defined as the interim PET-positive group, were associated with worse 5-y PFS and OS rates than the interim PET-negative group (for PFS: 52.0% vs. 80.7%, respectively, and P < 0.001; for OS: 56.2% vs. 81.4%, respectively, and P < 0.001). By multivariable analysis, the prognostic value of interim (18)F-FLT PET positivity by SUVmax remained significant after adjustment with other prognostic factors (for PFS: hazard ratio, 7.82, 95% confidence interval, 1.65-36.96, and P = 0.009; for OS: hazard ratio, 5.55, 95% confidence interval, 1.47-33.77, and P = 0.014).
In patients with aggressive NHL, early interim (18)F-FLT PET is a significant predictor of PFS and OS. Early (18)F-FLT PET imaging also has a potential to identify patients with delayed response and nonfavorable prognosis despite achieving a clinical complete response.
Journal of Nuclear Medicine 12/2013; · 5.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The 2011 Mw9.0 Tohoku earthquake generated infrasound that was recorded by nine infrasonic arrays. Most arrays recorded a back azimuth variation with time due to the expanse of the source region. We use ray tracing to predict group velocities and back azimuth wind corrections. A Japan accelerometer network recorded ground shaking in unprecedented spatial resolution. We back projected infrasound from arrays IS44 (Kamchatka) and IS30 (Tokyo) to the source region and compare these results with acceleration data. IS44 illuminates the complex geometry of land areas that experienced shaking. IS30 illuminates two volcanoes and a flat area around the city of Sendai, where the maximum accelerations occurred. The arrays and epicentral region define three source-receiver profiles. The observed broadband energy transmission loss (TL) follows an exponential decay law. The best fitting model, which has parameters that are interpreted to include the effects of geometric spreading, scattering, and the maximum ratio of the effective sound speed in the stratosphere to that at the ground (accounts for stratospheric wind speed), yields a 65% variance reduction relative to predictions from a traditional TL relationship. This model is a simplified version of the model of Le Pichon et al. (2012), which yields an 83% variance reduction for a single frequency, implying that fine-scale atmospheric structure is required to explain the TL for stratospheric upwind propagation. Our results show that infrasonic arrays are sensitive to ground acceleration in the source region of megathrust earthquakes. The TL results may improve infrasonic amplitude scaling laws for explosive yield.
Journal of Geophysical Research 12/2013; 118. · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anthrax is caused by the spore-forming bacterium Bacillus anthracis-, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (Alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (Malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (Protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Continuous exposure to commensal bacteria gives rise to a complex intestinal immune system that maintains local tolerance, which requires Foxp3-expressing Treg. Recently, the regulation of TFH function by plasma cells has been reported, but effects of intestinal LP-PCs, one of the richest plasma cells in the body, on T cell differentiation have not been studied. Here, we investigated whether IgA(+) LP-PCs from murine small intestines had effects on T cell differentiation. Surprisingly, when IgA(+) LP-PCs were cocultured with CD4(+) T cells, Foxp3 expression was increased significantly in CD4(+)CD25(-) T cells. Results using the Transwell coculture system revealed that soluble factors from LP-PCs, TGF-β, and RA were involved in the induction of Foxp3 expression. Furthermore, Foxp3(+)CD25(-) T cells were decreased in PP after intestinal depletion of plasma cells. In addition, intestinal colony transfer from SPF to germ-free mice was demonstrated to generate IgA(+) LP-PCs and Foxp3(+) T cells with meaningful correlation in LP. We report for the first time that IgA(+) LP-PCs induce Foxp3 expression in T cells through TGF-β and RA. LP-PCs generated by commensal bacteria may play a crucial role in intestinal immunity through the induction of Treg, as well as IgA production.
Journal of leukocyte biology 11/2013; · 4.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the usefulness of diffusion-weighted (DW) magnetic resonance images for distinguishing non-neoplastic cysts from solid masses of indeterminate internal characteristics on computed tomography (CT) in the mediastinum.
We enrolled 25 patients with pathologically proved mediastinal masses who underwent both thoracic CT and magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI). MRI was performed in patients with mediastinal masses of indeterminate internal characteristics on CT. Two thoracic radiologists evaluated the morphological features and quantitatively measured the net enhancement of the masses at CT. They also reviewed MR images including unenhanced T1- and T2-weighted images, gadolinium-enhanced images and DW images.
The enrolled patients had 15 solid masses and ten non-neoplastic cysts. Although the morphological features and the extent of enhancement on CT did not differ significantly between solid and cystic masses in the mediastinum (P > 0.05), non-neoplastic cysts were distinguishable from solid masses by showing signal suppression on high-b-value DW images or high apparent diffusion coefficient (ADC) values of more than 2.5 × 10(-3) mm(2)/s (P < 0.001). ADC values of non-neoplastic cysts (3.67 ± 0.87 × 10(-3) mm(2)/s) were significantly higher than that of solid masses (1.46 ± 0.50 × 10(-3) mm(2)/s) (P < 0.001).
DWI can help differentiate solid and cystic masses in the mediastinum, even when CT findings are questionable.
• Non-invasive diagnosis of non-neoplastic cysts can save surgical biopsy or excision. • Conventional CT or MRI findings cannot always provide a confident diagnosis. • Mediastinal masses can be well-characterised with DWI. • Non-neoplastic mediastinal cysts show significantly higher ADC values than cystic tumours. • DWI is useful to determine treatment strategy.
[Show abstract][Hide abstract] ABSTRACT: F-Fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) has been used for evaluation of the response of rectal cancer to neoadjuvant chemoradiotherapy (CRT), but differentiating residual tumor from post-treatment changes remains a problem. We propose a voxel-based dual-time F-FDG PET parametric imaging technique for the evaluation of residual rectal cancer after CRT.
Eighty-six patients with locally advanced rectal cancer who underwent neoadjuvant CRT between March 2009 and February 2011 were selected retrospectively. Standard 60-min postinjection PET/CT scans followed by 90-min delayed images were coregistered by rigid-body transformation. A dual-time parametric image was generated, which divided delayed standardized uptake value (SUV) by 60-min SUV on a voxel-by-voxel basis. Maximum delayed-to-standard SUV ratios (DSR) measured on the parametric images as well as the percentage of SUV decrease from pre-CRT to post-CRT scans (pre/post-CRT response index) were obtained for each tumor and correlated with pathologic response classified by the Dworak tumor regression grade (TRG).
With respect to the false-positive lesions in the nine post-CRT patients with false-positive standard F-FDG scans in case groups who responded to therapy (TRG 3 or 4 tumors), eight were undetectable on dual-time parametric images (P<0.05). The maximum DSR showed significantly higher accuracy for identification of tumor regression compared with the pre/post-CRT response index in receiver-operating characteristic analysis (P<0.01). With a 1.25 cutoff value for the maximum DSR, 85.0% sensitivity, 95.5% specificity, and 93.0% overall accuracy were obtained for identification of good response.
A voxel-based dual-time parametric imaging technique for evaluation of post-CRT rectal cancer holds promise for differentiating residual tumor from treatment-related nonspecific F-FDG uptake.
Nuclear Medicine Communications 10/2013; · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malignant meningiomas are rare and have worse prognosis than benign meningiomas. We report our experience of a malignant meningioma and review relevant literature in an attempt to investigate the clinical features, treatment, and prognosis of these tumors.
Brain tumor research and treatment. 10/2013; 1(2):85-90.
[Show abstract][Hide abstract] ABSTRACT: It has long been recognized that bronchial schwannomas are extremely rare. As such, diagnosing tumors in this extraordinary location can sometimes be problematic.
We reviewed seven cases of bronchoscopically or surgically resected endobronchial schwannomas and evaluated their clinical and pathologic features.
The present study included five female and two male patients, with ages ranging from 16 to 81 years (mean age, 44.9 years). The clinical presentation varied according to tumor size and location. Patients with more centrally (trachea or main bronchus) located tumors experienced respiratory symptoms (80%) more often than patients with more peripherally (lobar or segmental bronchus) located tumors (0%). Histologically, the tumors were composed of spindle cells that stained with S100 protein. Some of the tumors showed typical Antoni A areas with Verocay body formation. Five of six patients (83.3%) underwent complete tumor removal by rigid bronchoscopy.
Pathologists should consider endobronchial schwannoma in the differential diagnosis of a spindle cell tumor involving the bronchus. Additionally, our results showed that rigid bronchoscopy is an effective tool for tumor removal in endobronchial schwannoma patients.
The Korean Journal of Pathology 08/2013; 47(4):326-31. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IL-12 and IL-18 are cytokines which are mainly secreted by endothelial cells and monocytes including dendritic cells. The well-known effects of IL-12 and IL-18 in the protection against bacteria and virus infection as well as tumor development are associated with their characteristics in synergistically driving the development of T helper type 1 (Th1) cells and inducing IFN-γ production. In this study, we compared the knockout effects of IL-12 and/or IL-18 genes on phenotypes and functional capabilities of dendritic cells (DCs) including their ability to polarize naive CD4(+) T cells. The expression levels of surface molecules such as MHC II, CD80, CD86 and ICOSL, and endocytic capacity were not significantly differences between DCs of wild type (WT) mice and double knockout (DKO) mice of IL-12p40 and IL-18. Additionally, DCs lacking IL-12p40 and/or IL-18 genes were equivalently efficient in inducing T cell proliferation, compared with the WT-DCs. Interestingly, IL-10 production significantly decreased in DKO-DCs, while production of other inflammation-related cytokines were unaffected in WT-DCs and DKO-DCs. Importantly, IL-12p40(-/-)-DCs and DKO-DCs severely impaired the ability to induce IFN-γ and IL-17 production from CD4(+) T cells. IL-18(-/-)-DCs also moderately decreased IL-17 production and IL-17-expressing CD4(+) T cells when co-cultured with CD4(+) T cells, demonstrating the involvement of IL-18 in driving IL-17 differentiation. Taken together, these results suggest the principal contribution of IL-12p40 in inducing Th1 and Th17 polarization, regardless of similar surface phenotypes of DCs.
[Show abstract][Hide abstract] ABSTRACT: Supratentorial hemangioblastomas (HBs) are rare, and pituitary stalk HBs are extremely uncommon; therefore, pituitary stalk evaluation is often overlooked. Herein, we report the development of pituitary stalk HB over a 20-year period and the importance of regular long-term follow up for patients with HBs.
Journal of Korean Neurosurgical Society 05/2013; 53(5):297-9. · 0.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adipose stem cells (ASCs) are pluripotent cells that can generate pure fat tissue for regeneration. Differentiated adipose cells have been generated by a common inducer cocktail composed of dexamethasone, insulin, and isobutylmethylxanthine (DIM). The major drawbacks of adipose cells are their tendency to float on the culture media and their cost. To overcome some of these disadvantages, a new inducer cocktail that includes insulin, dehydroepiandrosterone, and histamine (DH IH) was tested. As a result, lipid accumulation was elevated more than twofold with DH IH than with DIM. Cell adhesion and viability, which are important factors for stable differentiation, were increased with DH IH and were proven through measurement of mRNA expression levels of adhesion marker genes, N-cadherin and vascular cell adhesion molecule, as well as through an alamar blue assay. The expression of adipogenesis-related genes, adiponectin, and glucose transporter type 4 lasted for a long time. To improve the efficiency of grafting, cell adhesion and neovascularization need to be increased. Neovascularization was observed around the transplanted adipose cells, which showed a higher number of vessel formation in DH IH than in DIM. The above results suggest that DH IH can produce pure differentiated adipose cells effectively and enhance their adhesion onto the target location when these differentiated adipose cells were applied as a clinical resource.
Biotechnology and Applied Biochemistry 05/2013; 60(3):356-64. · 1.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
Photo-gamma fusion lymphoscintigraphy (PGFLS) was developed by overlying a conventional planar gamma image on a photograph for the guidance of sentinel node biopsy. The feasibility and accuracy of PGFLS was assessed in breast cancer patients.
A digital camera and a gamma camera were coordinated to obtain photograph and gamma images from the same angle. Using the distance to the object and calibration acquisition with a flat phantom and radioactive markers, PGFLS was performed both in phantom and in patients without fiducial markers. Marker-free PGFLS was verified using flat phantom, anthropomorphic phantom with markers simulating sentinel nodes and breast cancer patients. In addition, the depth of the radioactive marker or sentinel node was calculated using two gamma images taken at right angles. The feasibility and accuracy of PGFLS were assessed in terms of mismatch errors of co-registration and depth with reference to the data from SPECT/CT.
The mismatch error was less than 6 mm in the flat phantom image at a distance from 50 to 62 cm without misalignment. In the anthropomorphic phantom study, co-registration error was 0.42 ± 0.29 cm; depth error was 0.51 ± 0.37 cm, which was well correlated with the reference value on SPECT/CT (x scale: R2 = 0.99, p < 0.01; y scale: R2 = 0.99, p < 0.01; depth: R2 = 0.99, p < 0.01). In ten patients with breast cancer referred for lympho-SPECT/CT, PGFSL enabled photo-guided sentinel lymph node mapping with acceptable accuracy (co-registration error, 0.47 ± 0.24 cm; depth error, 1.20 ±0.41 cm). The results from PGFSL showed close correlation with those from SPECT/CT (x scale: R2 = 0.99, p < 0.01; y scale: R2 = 0.98, p < 0.01; depth: R2 = 0.77, p < 0.01).
The novel and convenient PGFLS technique is clinically feasible, showing acceptable accuracy and providing additional visual and quantitative information for sentinel lymph node mapping. This approach will facilitate photo-guided sentinel lymph node dissection in breast cancer.
Nuclear Medicine and Molecular Imaging. 03/2013; 47(1).
[Show abstract][Hide abstract] ABSTRACT: Erythroid differentiation regulator 1 (Erdr1) suppressed cell motility in vitro and has anti-metastatic effect in vivo on melanoma. The current study investigated the effect of recombinant Erdr1 on the migration and invasion ability of SNU-216 cell, a gastric cancer cell line. The expression of Erdr1 is inversely correlated with IL-18 expression, which has a pro-cancer effect in gastric cancer. Treatment with rErdr1 markedly suppressed the ability of SNU-216 cells to migrate and invade, indicating that recombinant Erdr1 inhibited the motility of gastric cancer cells. E-cadherin expression levels were measured to determine the factor involved in the rErdr1-suppressed motility. E-cadherin is a representative of the cadherin family, known as cell motility enhancement adhesion molecule. Our results revealed that E-cadherin levels were increased by rErdr1 treatment, suggesting the involvement of E-cadherin in rErdr1-reduced cell migration. The cells were treated with specific MAPK inhibitors such as SP600125, SB203580 or PD98059 to identify the signaling mechanism involved with rErdr1 suppressed cell migration. The results indicated that the rErdr1 inhibited migration was primarily reversed by SP600125, a JNK inhibitor. In addition, the level of JNK phosphorylation was markedly increased by recombinant Erdr1. Taken together, these findings suggest that rErdr1 suppressed the ability of gastric cancer cells to metastasis by up regulating E-cadherin through a JNK pathway activation. Furthermore, it can be suggested that the inhibitory effect of recombinant Erdr1 on SNU-216 cell's metastatic potential was through cell motility suppression.