Evaluation of Infliximab Effects on Gastrointestinal Bleeding in Crohn's Disease Using Double-Balloon Endoscopy

Tumor necrosis factor α plays an important role in the pathogenesis of Crohn's disease (CD). The effects of infliximab on gastrointestinal bleeding in CD have not yet been fully evaluated. Herein we describe three CD cases who presented with gastrointestinal bleeding and received infliximab treatment. In case 1, double-balloon endoscopy showed a large ulcer with several irregularly shaped ulcers in the terminal ileum; 8 weeks after infliximab administration, complete healing of all lesions was observed. In case 2, double-balloon endoscopy showed linear ulcers and mucosal edema in the jejunum and ileum; 5 weeks after infliximab administration, all lesions were decreased in size and were healed. In case 3, double-balloon endoscopy revealed ulcerations and stenosis in the terminal ileum; 12 weeks after infliximab administration, ulcer healing and an increased diameter of the ileal stenosis were observed. These three cases have been receiving ongoing infliximab maintenance therapy and are currently symptom-free. Infliximab thus appears to be useful for treatment of gastrointestinal bleeding in CD patients

Thermal neutron flux evaluation by a single crystal CVD diamond detector in LHD deuterium experiment

The single crystal CVD diamond detector (SDD) was installed in the torus hall of the Large Helical Device (LHD) to measure neutrons with high time resolution and neutron energy resolution. The LiF foil with 95.62 % of 6Li isotope enrichment pasted on the detector was used as the thermal neutron convertor as the energetic ions of 2.0 MeV alpha and 2.7 MeV triton particles generated in LiF foil and deposited the energy into SDD. SDD were exposed to the neutron field in the torus hall of the LHD during the 2nd campaign of the deuterium experiment. The total pulse height in SDD was linearly propotional to the neutron yield in a plasma operation in LHD over 4 orders of magnitude. The energetic alpha and triton were separately measured by SDD with LiF with the thickness of 1.9 μm, although SDD with LiF with the thickness of 350 μm showed a broadened peak due to the large energy loss of energetic particles generated in the bulk of LiF. The modeling with MCNP and PHITS codes well interpreted the pulse height spectra for SDD with LiF with different thicknesses. The results above demonstrated the sufficient time resolution and energy discrimination of SDD used in this work

Potential of imaging analysis in establishing skin concentration-distance profiles for topically applied FITC-dextran 4 kDa

Quantitatively determining the skin concentration-distance profiles of topically applied drugs is important for evaluating their safety and efficacy. The aim of the present study was to quantitatively visualize the distribution of hydrophilic drugs through the skin using confocal laser scanning microscopy (CLSM) in order to obtain skin concentration-distance profiles. FITC-dextran with a molecular weight of approximately 4 kDa (FD-4) was selected as the model fluorescent drug in the present study, and excised pig ear skin was used. The skin concentration of FD-4 at each depth of a skin section was assessed by imaging analysis of the intensity of fluorescence. The FD-4 skin concentration-distance profile obtained was analyzed using Fick’s second law of diffusion, and was markedly similar to that using skin permeation parameters in the skin permeation study. These results suggest that the present CLSM method may be a promising tool for quantitatively visualizing the concentration-distance profiles of drugs through the skin

Single nucleosome imaging reveals loose genome chromatin networks via active RNA polymerase II.

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nagashima, R., Hibino, K., Ashwin, S. S., Babokhov, M., Fujishiro, S., Imai, R., Nozaki, T., Tamura, S., Tani, T., Kimura, H., Shribak, M., Kanemaki, M. T., Sasai, M., & Maeshima, K. Single nucleosome imaging reveals loose genome chromatin networks via active RNA polymerase II. Journal of Cell Biology, 218(5), (2019):1511-1530, doi:10.1083/jcb.201811090.Although chromatin organization and dynamics play a critical role in gene transcription, how they interplay remains unclear. To approach this issue, we investigated genome-wide chromatin behavior under various transcriptional conditions in living human cells using single-nucleosome imaging. While transcription by RNA polymerase II (RNAPII) is generally thought to need more open and dynamic chromatin, surprisingly, we found that active RNAPII globally constrains chromatin movements. RNAPII inhibition or its rapid depletion released the chromatin constraints and increased chromatin dynamics. Perturbation experiments of P-TEFb clusters, which are associated with active RNAPII, had similar results. Furthermore, chromatin mobility also increased in resting G0 cells and UV-irradiated cells, which are transcriptionally less active. Our results demonstrated that chromatin is globally stabilized by loose connections through active RNAPII, which is compatible with models of classical transcription factories or liquid droplet formation of transcription-related factors. Together with our computational modeling, we propose the existence of loose chromatin domain networks for various intra-/interchromosomal contacts via active RNAPII clusters/droplets.We thank Dr. Y. Hiromi, Dr. S. Hirose, Dr. H. Seino, and Dr. S. Ide for critical reading of this manuscript. We thank Dr. S. Ide, Dr. D. Kaida, Dr. T. Nagai, Dr. V. Doye, Dr. G. Felsenfeld, and Dr. K. Horie for valuable help and materials. We also thank the Maeshima laboratory members for helpful discussions and support. R. Imai and T. Nozaki are Japan Society for the Promotion of Science Fellows. R. Nagashima was supported by 2017 SOKENDAI Short-Stay Study Abroad Program. This work was supported by a Japan Society for the Promotion of Science grant (16H04746), Takeda Science Foundation, RIKEN Pioneering Project, a Japan Science and Technology Agency Core Research for Evolutional Science and Technology grant (JPMJCR15G2), a National Institute of General Medical Sciences grant (R01-GM101701), and National Institute of Genetics JOINT (2016-A2 (6))

Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis

A variety of neuronal surface (NS) antibodies (NS-Ab) have been identified in autoimmune encephalitis (AE). Tissue-based assay (TBA) using a rodent brain immunohistochemistry (IHC) is used to screen NS-Ab, while cell-based assay (CBA) to determine NS antigens. Commercial rat brain IHC is currently available but its clinical relevance remains unclear. Immunostaining patterns of NS antigens have not been extensively studied yet. To address these issues, we assessed a predictive value of “neuropil pattern” and “GFAP pattern” on commercial IHC in 261 patients, and characterized an immunostaining pattern of 7 NS antigens (NMDAR, LGI1, GABAaR, GABAbR, AMPAR, Caspr2, GluK2). Sensitivity and specificity of “neuropil pattern” for predicting NS-Ab were 66.0% (95% CI 55.7-75.3), and 98.2% (95% CI 94.8-99.6), respectively. False-positive rate was 1.8% (3/164) while false-negative rate was 34.0% (33/97). In all 3 false-positive patients, neuropil-like staining was attributed to high titers of GAD65-Ab. In 33 false-negative patients, NMDAR was most frequently identified (n=18 [54.5%], 16/18 [88.9%] had low titers [< 1:32]), followed by GABAaR (n=5). Of 261 patients, 25 (9.6%) had either GFAP (n=21) or GFAP-mimicking pattern (n=4). GFAP-Ab were identified in 21 of 31 patients examined with CBA (20 with GFAP pattern, 1 with GFAP-mimicking pattern). Immunostaining pattern of each NS antigen was as follows: 1) NMDAR revealed homogenous reactivity in the dentate gyrus molecular layer (DG-ML) with less intense dot-like reactivity in the cerebellar granular layer (CB-GL); 2) both GABAaR and GluK2 revealed intense dot-like reactivity in the CB-GL, but GABAaR revealed homogenous reactivity in the DG-ML while GluK2 revealed intense reactivity along the inner layer of the DG-ML; and 3) LGI1, Caspr2, GABAbR, and AMPAR revealed intense reactivity in the cerebellar ML (CB-ML) but LGI1 revealed intense reactivity along the middle layer of the DG-ML. Whereas, Caspr2, GABAbR, and AMPAR revealed similar reactivity in the DG-ML but some difference in other regions. TBA is useful not only for screening NS- or GFAP-Ab but also for estimating NS antigens; however, negative results should be interpreted cautiously because “neuropil pattern” may be missed on commercial IHC when antibody titers are low. Antigen-specific immunoreactivity is a useful biomarker of AE

Current status of Japanese detectors

Current status of TAMA and CLIO detectors in Japan is reported in this article. These two interferometric gravitational-wave detectors are being developed for the large cryogenic gravitational wave telescope (LCGT) which is a future plan for detecting gravitational wave signals at least once per year. TAMA300 is being upgraded to improve the sensitivity in low frequency region after the last observation experiment in 2004. To reduce the seismic noises, we are installing new seismic isolation system, which is called TAMA Seismic Attenuation System, for the four test masses. We confirmed stable mass locks of a cavity and improvements of length and angular fluctuations by using two SASs. We are currently optimizing the performance of the third and fourth SASs. We continue TAMA300 operation and R&D studies for LCGT. Next data taking in the summer of 2007 is planned. CLIO is a 100-m baseline length prototype detector for LCGT to investigate interferometer performance in cryogenic condition. The key features of CLIO are that it locates Kamioka underground site for low seismic noise level, and adopts cryogenic Sapphire mirrors for low thermal noise level. The first operation of the cryogenic interferometer was successfully demonstrated in February of 2006. Current sensitivity at room temperature is close to the target sensitivity within a factor of 4. Several observation experiments at room temperature have been done. Once the displacement noise reaches at thermal noise level of room temperature, its improvement by cooling test mass mirrors should be demonstrated.Comment: 6 pages, 5 figures, Proceedings of GWDAW-1