Computer simulations on the initiation and morphological difference of Japan winter and summer sprites

[1] Two‐dimensional (axisymmetric) computer simulations (electromagnetic code) have been performed to study the initiation and morphological difference (summer, carrots, and winter, columns) of sprites for simulating Japan summer and winter sprites. By changing the physical parameters of a parent lightning, we have found the following findings by looking at the spatial‐temporal distribution of reduced electric field, etc. (1) There are three important factors (the height where the charge is removed (ds), charge transfer (Q), and lightning current risetime (τ)) in the initiation of sprites and their morphological differences. (2) For the initiation of sprites, the charge transfer (Q) should exceed a certain value for possible charge heights (giving us a threshold of charge moment change (Qds) of the order of ∼120–200 C·km), with a combination of small risetime of lightning current waveform. (3) Further, the height for positive charge is much higher than that for negative charge in a typical lightning configuration, which is the essential factor in determining the morphological difference of sprites in summer and winter. Positive charges for summer are located at a much higher altitude than those in winter in Japan, which might result in carrot‐type in summer and columnar‐type in winter even for the same positive polarity. (4) A combinational effect of (Ids) and (Qds) is important for having sprites. Finally, the present computer results on the initiation of sprites for Japanese lightning have been compared extensively to the well‐documented properties of summer continental sprites and future subjects to study have been suggested

NPSLE患者の髄液中補体第３成分（C3）と炎症マーカーに関する検討

博士（医学）福島県立医科大

A Case of Severe Esophageal Intramural Pseudodiverticulosis Whose Symptoms Were Ameliorated by Oral Administration of Anti-Fungal Medicine

Esophageal intramural pseudodiverticulosis (EIPD) is a rare disease of unknown etiology that displays multiple pseudodiverticula radiologically, leading to benign esophageal stricture. Dysphagia, which sometimes slowly progresses, is the main symptom in the majority of cases. We here report a 59-year-old male EIPD patient who suffered from severe dysphagia. Radiography and endoscopy of this patient disclosed a severe constriction in the upper thoracic esophagus. Although we tried several endoscopic procedures including frequent endoscopic balloon dilatation (EBD), the effect was very limited and his dysphagia relapsed shortly after the treatments. During the procedures, we noticed some white, thick, creamy liquid emerging from the orifices of EIPD, and PAS staining of biopsy specimens revealed infection with Candida albicans. Hence, the patient was given anti-fungal medicine in addition to EBD. The additional treatment with anti-fungal medicine dramatically improved his symptoms and the esophageal constriction. This case suggests that anti-fungal treatment is an effective first-line therapy even against a severe form of esophageal constriction in EIPD

Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Fas(lpr/lpr) Mice

Objective: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus. Methods: We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr/J mice. We performed 3′ untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223−/−Faslpr/lpr mice and the lupus phenotypes were analyzed. Results: In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr/J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3′ UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223−/−Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8− cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223+/+Faslpr/lpr mice by flow cytometry. B6-Mir223−/−Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells. Conclusion: Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis

Familial Mediterranean fever phenotype progression into anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis:a case report

Familial Mediterranean fever (FMF) is caused by dysfunction of the MEFV gene product, pyrin. Here we report a case of FMF phenotype which developed into rheumatoid arthritis (RA), based on a positive result for anti-cyclic citrullinated peptide (CCP) antibody (Ab). A 42-year-old woman presented to our clinic with more than 6 months of intermittent arthralgia in the wrists, feet, and fingers associated with menstruation. No fever was reported and there was no family history of FMF or other autoimmune diseases. Laboratory tests revealed elevated C-reactive protein (CRP) and rheumatoid factor (RF). Tests for autoantibodies including anti-CCP Ab, antinuclear Ab, and anti-DNA Ab were all negative. Genetic analysis identified an R304R homozygous mutation in MEFV; however, the pathological significance is unclear because this mutation does not cause amino acid substitution. We diagnosed incomplete FMF phenotype despite the lack of fever due to periodic arthritis, lack of autoantibodies, and complete resolution of arthritis following colchicine treatment within a day. Several months later, increased stiffness and arthralgia persistently occurred in finger joints on both sides. Ultrasonography revealed synovitis at the metacarpophalangeal and metatarsophalangeal joints. Laboratory analysis revealed the patient to be positive for anti-CCP Ab. Therefore, we finally diagnosed RA. Her arthritis diminished following administration of methotrexate and salazosulfapyridine. We consider the possibility that pyrin dysfunction may have affected the acquired immunity, contributing to the onset of RA as an autoimmune disease. This is an interesting case of equivalent FMF progressing into RA and will be valuable to raise awareness of a continuum from autoinflammatory to autoimmune disease

Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo

<p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the ¹⁰B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface. To extend the therapeutic use of BNCT from surface tumors to visceral tumors will require ¹⁰B compounds that accumulate strongly in tumor cells without significant accumulation in normal cells, and an appropriate delivery method for deeper tissues.</p> <p>Hemagglutinating Virus of Japan Envelope (HVJ-E) is used as a vehicle for gene delivery because of its high ability to fuse with cells. However, its strong hemagglutination activity makes HVJ-E unsuitable for systemic administration.</p> <p>In this study, we developed a novel vector for ¹⁰B (sodium borocaptate: BSH) delivery using HVJ-E and cationized gelatin for treating multiple liver tumors with BNCT without severe adverse events.</p> <p>Methods</p> <p>We developed cationized gelatin conjugate HVJ-E combined with BSH (CG-HVJ-E-BSH), and evaluated its characteristics (toxicity, affinity for tumor cells, accumulation and retention in tumor cells, boron-carrying capacity to multiple liver tumors <it>in vivo</it>, and bio-distribution) and effectiveness in BNCT therapy in a murine model of multiple liver tumors.</p> <p>Results</p> <p>CG-HVJ-E reduced hemagglutination activity by half and was significantly less toxic in mice than HVJ-E. Higher ¹⁰B concentrations in murine osteosarcoma cells (LM8G5) were achieved with CG-HVJ-E-BSH than with BSH. When administered into mice bearing multiple LM8G5 liver tumors, the tumor/normal liver ratios of CG-HVJ-E-BSH were significantly higher than those of BSH for the first 48 hours (<it>p < 0.05</it>). In suppressing the spread of tumor cells in mice, BNCT treatment was as effective with CG-HVJ-E-BSH as with BSH containing a 35-fold higher ¹⁰B dose. Furthermore, CG-HVJ-E-BSH significantly increased the survival time of tumor-bearing mice compared to BSH at a comparable dosage of ¹⁰B.</p> <p>Conclusion</p> <p>CG-HVJ-E-BSH is a promising strategy for the BNCT treatment of visceral tumors without severe adverse events to surrounding normal tissues.</p

Signet Ring Cell Gastric Cancer Occurring after Radiation Therapy for Helicobacter pylori-Uninfected Mucosa-Associated Lymphoid Tissue Lymphoma

Helicobacter pylori infection is the major cause for mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancers. On the other hand, gastric cancers are known to arise from gastric mucosal atrophy. We here report a case of signet ring cell gastric cancer that developed after radiation therapy for MALT lymphoma in H. pylori-uninfected patient whose stomach did not show gastric mucosal atrophy. A 58-year-old female was referred to our hospital for treatment of gastric MALT lymphoma. This patient was not infected with H. pylori, and upper gastrointestinal endoscopy revealed that she did not have gastric mucosal atrophy but had submucosal tumor-like MALT lymphoma lesion in the anterior wall of the upper gastric body. Since conventional eradication therapy was ineffective, her whole stomach was irradiated as a second-line therapy. The MALT lymphoma lesion turned into complete remission state after the therapy. The patient was followed every 6 months by upper gastrointestinal endoscopy for 4 years as complete remission until a newly developed decolorized depressed lesion was detected in the greater curvature of the proximal antrum, a completely different location from the MALT lymphoma lesion. A biopsy specimen from the lesion contained signet ring cell carcinoma, and she was successfully treated by endoscopic submucosal dissection. No signs of recurrence have been detected so far. The radiation therapy for MALT lymphoma might be associated with the occurrence of this signet ring cell gastric cancer, and since MALT lymphoma is indolent in nature, this case suggests that careful consideration is required when choosing the second-line therapy for MALT lymphoma patients