The aim of this study was to clarify the correlation between imaging findings obtained using intraoral ultrasonography (US) and pathological findings of tongue cancers, and to examine the predictive ...value of intraoral US findings with respect to occult nodal metastasis. This was a retrospective study based on the medical records of 123 patients with T1–2N0 tongue cancer. The depth of invasion (DOI) on intraoral US was positively correlated with the pathological invasion depth (PID) (ρ = 0.7080, P < 0.0001). Receiver operating characteristic analyses revealed an optimal DOI cut-off value of 4.1 mm and optimal PID cut-off value of 3.9 mm to detect nodal metastasis. Regarding the margin shape of the primary tumour on intraoral US, the incidence of nodal metastasis was significantly higher for the permeated type than for the pressure type (P < 0.001) and wedge-shaped type (P = 0.002). Furthermore, tumours with peritumoural vascularity assessed by power Doppler US had a significantly higher incidence of nodal metastasis than tumours without (P = 0.003). The sensitivity, specificity, and accuracy of the permeated type to predict nodal metastasis was 53.6%, 95.8%, and 86.2%, respectively. These results suggest that intraoral US findings closely reflect pathological findings and could be useful to predict occult nodal metastasis in patients with early-stage tongue cancer.
Background and Objective
Bacteria in the dental biofilm surrounding marginal gingival grooves cause periodontal diseases. Numerous bacteria within the biofilm consume nutrients from the gingival ...crevicular fluid. Furthermore, some gram‐negative bacteria in mature dental biofilms produce butyrate. Thus, gingival epithelial cells in close proximity to mature dental biofilms are at risk of both starvation and exposure to butyrate. In the present study, we determined the combined effects of starvation and butyrate exposure on gingival epithelial cell death and the underlying mechanisms.
Material and Methods
The Ca9‐22 cell line was used as an in vitro counterpart of gingival epithelial cells. Cell death was measured as the amount of total DNA in the dead cells using SYTOX Green dye, which penetrates through membranes of dead cells and emits fluorescence when it intercalates into double‐stranded DNA. AMP‐activated protein kinase (AMPK) activity, the amount of autophagy, and acetylation of histone H3 were determined using western blot. Gene expression levels of microtubule‐associated protein 1 light chain 3b (lc3b) were determined using quantitative reverse transcription–polymerase chain reaction.
Results
Butyrate‐induced cell death occurred in a dose‐dependent manner whether cells were starved or fed. However, the induction of cell death was two to four times higher when cells were placed under starvation conditions compared to when they were fed. Moreover, both starvation and butyrate exposure induced AMPK activity and autophagy. While AMPK inactivation resulted in decreased autophagy and butyrate‐induced cell death under conditions of starvation, AMPK activation resulted in butyrate‐induced cell death when cells were fed. Combined with the results of our previous report, which demonstrated butyrate‐induced autophagy‐dependent cell death, the results of this study suggest that the combination of starvation and butyrate exposure activates AMPK inducing autophagy and subsequent cell death. Notably, this combination markedly induced LC3B production and the induction was attenuated by AMPK inhibition. LC3B knockdown, in turn, significantly decreased butyrate‐induced cell death. Therefore, AMPK‐dependent LC3B induction apparently plays an important role in butyrate‐induced cell death. There was a lack of correspondence between the levels of AMPK activation and LC3B induction; this may reflect the histone deacetylase‐inhibitory capacity of butyrate on histone proteins.
Conclusion
Taken together, starvation and butyrate exposure promote autophagy via AMPK signaling, while the histone deacetylase‐inhibitory effects of butyrate alter chromatin to transcriptionally active state, resulting in strong LC3B induction and subsequent cell death. These findings may help improve the understanding of the cellular processes underlying periodontal disease initiation.
Inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene causes both hereditary and sporadic clear-cell renal-cell carcinoma (ccRCC). Although the best-characterized function of the VHL ...protein (pVHL) is regulation of hypoxia-inducible factor-α (HIFα), pVHL also controls the development of pheochromocytoma through HIF-independent pathways by regulating JunB. However, it is largely unknown how these pathways contribute to the development and progression of ccRCC. In the present study, we confirmed that JunB was upregulated in VHL-defective ccRCC specimens by immunostaining. Short-hairpin RNA (shRNA)-mediated knockdown of JunB in 786-O and A498 VHL null ccRCC cells suppressed their invasiveness. In addition, JunB knockdown significantly repressed tumor growth and microvessel density in xenograft tumor assays. Conversely, forced expression of wild-type, but not dimerization-defective, JunB in a VHL-restored 786-O subclone promoted invasion in vitro and tumor growth and vessel formation in vivo. Quantitative PCR array analysis revealed that JunB regulated multiple genes relating to tumor invasion and angiogenesis such as matrix metalloproteinase-2 (MMP-2), MMP-9 and chemokine (C-C motif) ligand-2 (CCL2) in 786-O cells. JunB knockdown in these cells reduced the proteolytic activity of both MMPs in gelatin zymography and the amount of CCL2 in the culture supernatant. Moreover, shRNA-mediated knockdown of MMP-2 or inhibition of CCL2 activity with a neutralizing antibody repressed xenograft tumor growth and angiogenesis. Collectively, these results suggest that JunB promotes tumor invasiveness and enhances angiogenesis in VHL-defective ccRCCs.
The hypothesis of helper T (T(h))1/T(h)2 cytokine balance proposed by Mosmann and Coffman is often invoked to explain the development of inflammatory diseases, including inflammatory bowel diseases ...(IBD). Recently, however, a newly identified class of T(h) cells-T(h)17 cells, which produce T(h)17 family cytokines-has been recognized as an essential subpopulation in the development of almost all kinds of human and animal inflammatory diseases, rather than T(h)1 and T(h)2 cells. A representative T(h)17 family cytokine, interleukin (IL)-17A, is produced by not only T(h)17 cells, but also by other types of cells, such as T-cell receptor γδ T cells, natural killer (NK) T cells, NK cells, myeloid cells, and innate lymphoid cells, which may also be critically involved in the initiation and persistence of IBD. Here we review recent advances in the study of such IL-17A-producing cells in the pathogenesis of IBD.
JLDG is a data-grid for the lattice QCD (LQCD) community in Japan. Several large research groups in Japan have been working on lattice QCD simulations using supercomputers distributed over distant ...sites. The JLDG provides such collaborations with an efficient method of data management and sharing. File servers installed on 9 sites are connected to the NII SINET VPN and are bound into a single file system with the GFarm. The file system looks the same from any sites, so that users can do analyses on a supercomputer on a site, using data generated and stored in the JLDG at a different site. We present a brief description of hardware and software of the JLDG, including a recently developed subsystem for cooperating with the HPCI shared storage, and report performance and statistics of the JLDG. As of April 2015, 15 research groups (61 users) store their daily research data of 4.7PB including replica and 68 million files in total. Number of publications for works which used the JLDG is 98. The large number of publications and recent rapid increase of disk usage convince us that the JLDG has grown up into a useful infrastructure for LQCD community in Japan.
Weld residual stress affects joint performance in terms of the fatigue life and resistance to stress corrosion cracking. Thus far, the weld residual stress has been discussed mainly at the scale of ...the joint—the macroscopic scale. However, the weld residual stress can be inhomogeneous at the microscopic scale like a crystal grain; this aspect has not been discussed well. In this study, a numerical simulation model was developed to calculate the inhomogeneous distribution of the microscopic residual stress, based on the both-ends-fixed bar model. The bar was modeled by a polycrystalline aggregate, and the elastic and plastic anisotropy were defined for each grain. Thermal cycles with various peak temperatures were applied on the both-ends-fixed polycrystalline bar, and the evolution of the microscopic stress was simulated. The elastic and plastic anisotropy of the grains affected the inhomogeneity of the microscopic stress distribution. Elastic anisotropy caused inhomogeneity under elastic loading, whereas plastic anisotropy affected that under plastic loading. It was demonstrated that a microscopic stress higher than the applied macroscopic stress was generated when anisotropy was taken into consideration.
Protease-activated receptor 1 (PAR1) is known as a thrombin receptor. Recent studies have reported PAR1 expression in various malignancies; however, its role in oral squamous cell carcinoma (OSCC) ...requires clarification. A previous study showed that down-regulation of ΔNp63, a homolog of p53, augments PAR1 expression in OSCC. In the present study, the association of PAR1 expression with clinicopathological findings in OSCC was examined retrospectively. Expression of PAR1, thrombin, and ΔNp63 was examined immunohistochemically in OSCC specimens. Patients were divided into three groups based on the expression pattern of PAR1 at the invasive front: group A, PAR1-negative in both cancer and stromal cells; group B, positive in stromal cells but negative in cancer cells; group C, positive in both cancer and stromal cells. Histologically high-grade tumours were significantly more common in group C. Patients in group C had the highest incidence rate of nodal metastasis (P<0.001) and a lower survival rate (P=0.085) than those in the other groups. At the invasive front, in group C, thrombin was expressed but ΔNp63 expression was weak. These results indicate that increased PAR1 expression in both cancer and stromal cells could be a useful predictive marker of nodal metastasis and that ΔNp63 is involved in regulating PAR1 expression.
Abstract
A new High-Temperature Superconducting ECR (HTS-ECR) ion source is under development in Research Center for Nuclear Physics (RCNP), Osaka University. This ion source will be used for ...production of high intensity proton, deuteron and He ion beams. The HTS-ECR magnets are composed of three solenoid coils and a set of sextupole coils made of REBCO tapes, a high-temperature superconductor. The HTS-ECR ion source is designed to operate at frequency of 2.45 GHz and 10 GHz. Performance test of the HTS coils had been carried out at 31 K and 77 K. This HTS coil technology will be applied to development of a meter-size HTS coil system of a high intensity compact AVF cyclotron. This paper introduces the basic design of the HTS-ECR ion source. The performance test results showed that REBCO solenoids remain superconducting state with a current up to 400 A. Simulation results of the magnetic field and electromagnetic field distributions in a plasma chamber fulfilled the requirements of electron cyclotron resonance conditions at 2.45 GHz and 10 GHz. Simulation result of mirror ratios and electromagnetic field amplitudes are also presented in this paper.
Objective
The study was designed to investigate the process of calcification during bone healing in a standardised rat calvarial bone defect model, measured by bone mineral density and the ...concentrations and distributions of calcium, phosphorus and carbon in the bone matrix.
Materials and methods
A standard defect was made on the parietal bone of 12‐week‐old rats under anaesthesia. The rats were fixed in weeks 1, 2, 4 and 8, and the calvaria were resected and examined with microcomputed tomography, then frozen and sectioned for histology and analysed with energy‐dispersive X‐ray spectroscopy (EDX). Parietal bone of 12‐week‐old control rats was processed similarly.
Results
The mineral density of healing bone increased with time. The healing bone became thicker and denser with time in histology. The distributions of Ca and P expanded over the bone matrix, whereas that of C became localised and complemented that of C and P. The Ca/P concentration ratio increased, whereas the C/Ca and C/P ratios decreased in the healing bone matrix.
Conclusion
Healing bone is immaturely calcified initially and proceeds calcification gradually, that is, as the bone volume increases, mineral increases in density and matures in quality, while organic components decrease.
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