Induction of Autoimmunity in a Bleomycin-Induced Murine Model of Experimental Systemic Sclerosis: An Important Role for CD4+ T Cells

Systemic sclerosis (SSc) is an autoimmune disease characterized by the excessive deposition of collagen in the skin or other organs and the production of specific antinuclear antibodies (ANAs). Recently, bleomycin (BLM)-induced experimental scleroderma was reported in a murine model. Here, we present further development of this model and suggest that it is appropriate for the analysis of human diffuse type SSc. BLM was injected into the shaved backs of C3H or BALB/c mice (100μg/mouse) 5 days per week for 3 weeks. Skin fibrosis was confirmed and pathological changes were seen in the lower part of the esophagus and stomach similar to those seen in SSc. The sera from these mice had autoantibodies specific to the damaged tissues and ANAs. Transfer of CD4+ T cells from BLM-treated BALB/c mice induced the same pathological changes and antibody production in untreated-BALB/c nude mice. Hence, tissue fibrosis and the production of ANAs are probably associated with CD4+ T-cell activity in this model. In conclusion, this model will be valuable for investigating the relationship between tissue fibrosis and abnormalities of the immune system

Changes in Angiotensin II Type 1 Receptor Expression in the Rat Bladder by Bladder Outlet Obstruction

Purpose: To demonstrate the change in the expression of angiotensin II type 1 receptor (AT1) in the rat bladder with partial bladder outlet obstruction (P-BOO). Materials and Methods: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups, a P-BOO group and a control group. The rats of the P-BOO group were divided into six groups: a sham-operated control group, 1 day postoperatively, 2 days postoperatively, 4 days postoperatively, 7 days postoperatively and 14 days postoperatively. The cystometric findings and immunohistochemical staining of the detrusor muscle with the AT1 antibody were compared in each group. Results: AT1 localized on the cell membrane of the detrusor smooth muscle and in cytoplasm of suburothelial myofibroblasts in the control rats. The expression of AT1 disappeared in the detrusor muscle and suburothelial myofibroblasts in P-BOO, but AT1 was highly expressed in urothelial cells 1 day after surgery. The expression of AT1 in urothelial cells gradually decreased with time after surgery. AT1 completely disappeared in urothelial cells 14 days after surgery. Conclusions: The present study demonstrated that the site of AT1 expression changes in response to the mechanical stress caused by P-BOO, and finally there was no expression of AT1 in rat bladder tissue following P-BOO. These data suggest the change in AT1 expression may play a role in bladder function

Large Population of ALMA Galaxies at z>6 with Very High [OIII]88um to [CII]158um Flux Ratios: Evidence of Extremely High Ionization Parameter or PDR Deficit?

We present our new ALMA observations targeting [OIII]88um, [CII]158um, [NII]122um, and dust continuum emission for three Lyman break galaxies at z=6.0293-6.2037 identified in the Subaru/Hyper Suprime-Cam survey. We clearly detect [OIII] and [CII] lines from all of the galaxies at 4.3-11.8sigma levels, and identify multi-band dust continuum emission in two of the three galaxies, allowing us to estimate infrared luminosities and dust temperatures simultaneously. In conjunction with previous ALMA observations for six galaxies at z>6, we confirm that all the nine z=6-9 galaxies have high [OIII]/[CII] ratios of L[OIII]/L[CII]~3-20, ~10 times higher than z~0 galaxies. We also find a positive correlation between the [OIII]/[CII] ratio and the Lya equivalent width (EW) at the ~90% confidence level. We carefully investigate physical origins of the high [OIII]/[CII] ratios at z=6-9 using Cloudy, and find that high density of the interstellar medium, low C/O abundance ratio, and the cosmic microwave background attenuation are responsible to only a part of the z=6-9 galaxies. Instead, the observed high [OIII]/[CII] ratios are explained by 10-100 times higher ionization parameters or low photodissociation region (PDR) covering fractions of 0-10%, both of which are consistent with our [NII] observations. The latter scenario can be reproduced with a density bounded nebula with PDR deficit, which would enhance the Lya, Lyman continuum, and C+ ionizing photons escape from galaxies, consistent with the [OIII]/[CII]-Lya EW correlation we find.Comment: 20 pages, 18 figures, Accepted for publication in Ap

Chemogenetic attenuation of cortical seizures in nonhuman primates

「てんかん」の発生を時間的・空間的にピンポイントで抑える画期的な治療法を開発 --世界で初めてサルでの有効性を実証、臨床応用に向け大きく前進--. 京都大学プレスリリース. 2023-03-01.Epilepsy is a disorder in which abnormal neuronal hyperexcitation causes several types of seizures. Because pharmacological and surgical treatments occasionally interfere with normal brain function, a more focused and on-demand approach is desirable. Here we examined the efficacy of a chemogenetic tool—designer receptors exclusively activated by designer drugs (DREADDs)—for treating focal seizure in a nonhuman primate model. Acute infusion of the GABAA receptor antagonist bicuculline into the forelimb region of unilateral primary motor cortex caused paroxysmal discharges with twitching and stiffening of the contralateral arm, followed by recurrent cortical discharges with hemi- and whole-body clonic seizures in two male macaque monkeys. Expression of an inhibitory DREADD (hM4Di) throughout the seizure focus, and subsequent on-demand administration of a DREADD-selective agonist, rapidly suppressed the wide-spread seizures. These results demonstrate the efficacy of DREADDs for attenuating cortical seizure in a nonhuman primate model

Expression of angiotensin II type 1 receptor in rat bladder smooth muscle cells in response to a streptzotocin induced diabetes mellitus model

Introduction: The aim of this study was to investigate angiotensin II type 1 (AT1) receptors in rat bladder smooth muscle cells and alterations of AT1 receptors by diabetes mellitus and diuretic states. Materials and Methods: Diabetes and diuresis were induced in adult female rats by a single intraperitoneal injection of streptozotocin and feeding 5% sucrose in water. Cystometry was performed on control, diuretic, and diabetic rats at 2 and 8 weeks after treatment. Immunohistochemical staining was used to detect expression of AT1 receptors in the bladder smooth muscle cell membrane. Results and Conclusions: In diabetic rats, expression of AT1 receptors in the bladder smooth muscle cell membrane increased at 2 weeks and further increased at 8 weeks. The local renin-angiotensin system in the rat bladder might be activated by the continuous hyperglycemia caused by intraperitoneal injection of streptozotocin administration

Management of Massive Arterial Hemorrhage After Pancreatobiliary Surgery: Does Embolotherapy Contribute to Successful Outcome?

Massive arterial hemorrhage is, although unusual, a life-threatening complication of major pancreatobiliary surgery. Records of 351 patients who underwent major surgery for malignant pancreatobiliary disease were reviewed in this series. Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was achieved in five patients and one patient, respectively. However, 7 of 13 cases ended in fatality, which is a 54% mortality rate. Among six survivors, one underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA). Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic inflow was maintained by successful TAE of the gastroduodenal artery in two and via a well-developed subphrenic artery in one. One patient had TAE of the celiac axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was maintained by the arcades around the pancreatic head. One patient who experienced a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re-laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In contrast, four of seven patients with fatal outcomes experienced hepatic infarction following TAE proximal to the PHA or injury of the common hepatic artery during angiography. One patient who underwent a major hepatectomy for hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal artery and experienced hepatic failure. In the two patients with a pseudoaneurysm of the SPA or the superior mesenteric artery, an emergency re-laparotomy was required to obtain hemostasis because of worsening clinical status. Selective TAE distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be restricted to cases where collateral hepatic blood flow exists. Otherwise or for a pseudoaneurysm of the superior mesenteric artery, endovascular stenting, temporary creation of an ileocolic arterioportal shunt, or vascular reconstruction by re-laparotomy is an alternative

Porous In2O3 powders prepared by ultrasonic-spray pyrolysis as a NO2-sensing material: Utilization of polymethylmethacrylate microspheres synthesized by ultrasonic-assisted emulsion polymerization as a template

NO2-sensing properties of porous In2O3 (pr-In2O3) powders prepared by ultrasonic-spray pyrolysis employing polymethylmethacrylate (PMMA) microspheres as a template has been investigated in this study. The PMMA microspheres were synthesized in water by ultrasonic-assisted emulsion polymerization employing methyl methacrylate monomer, sodium lauryl sulfate as a surfactant and ammonium persulfate as an initiator. The PMMA microspheres synthesized was quite uniform and the particle size was ca. 60.2 nm (measured by dynamic light scattering). The microstructure of pr-In2O3 powders prepared was largely dependent on the kind of In2O3 sources. The pr-In2O3 which was prepared from In(NO3)3 as an In 2O3 source (pr-In2O3(N)) consisted of submicron-sized spherical particles with welldeveloped spherical mesopores (several tens of nanometers in pore diameter) and each oxide wall among pores was constructed with meso-sized In2O3 particles connected continuously. On the other hand, the pr-In2O3 which was prepared from InCl3 as an In2O3 source (pr-In2 O3(Cl)) was composed of a large number of dispersed meso-sized particles and a few submicron-sized dense spherical particles. In contrast, the morphology of conventional In2O3 powder (c-In 2O3) prepared by ultrasonic-spray pyrolysis of PMMAfree In(NO3)3 aqueous solution as a reference was relatively dense and roughly spherical with a diameter of ca. 100-700 nm. The responses to 1.0 and 10ppm NO2 of pr-In2O3 sensors in air were much larger than those of a c-In2O3(N) sensor in the temperature range of less than 250°C and 300°C, respectively. In addition, the response and recovery speeds of both the pr-In2O 3 sensors were much faster than those of the c-In2O 3(N) sensor, because of the well-developed porous structure of the pr-In2O3 sensors

Organized and Sustainable Education Program for Drug Abuse Prevention by Yogo-teachers

　学校における喫煙・飲酒・薬物乱用防止教育の充実には，問題行動が顕在化する中学校期だけでなく小学校期 における指導の推進が重要であり，系統的な指導計画を立て，指導者や時間の確保，教材作成などに組織的に取 組み，継続可能なプログラム開発を行う必要がある。そこで，地区内12 校の養護教諭が協働して，発達段階に応 じた系統的・組織的かつ継続可能な地区共通の指導計画を開発し，各校の教育課程・年間計画に位置付けた実践 研究を行った。その結果，指導計画の実施状況は，小学校11 校中，学級活動10 校，ミニ保健指導10 校，長期 休業前指導6 校，広報活動9 校となり，特別支援学校1 校では広報活動のみを行うことができた。小学校におけ る喫煙・飲酒・薬物乱用防止教育の推進には，学校保健活動の中核的役割を担う養護教諭が専門性を活かし協働 して，系統的な指導計画を各校の教育課程に位置付け組織的で継続可能なプログラムとする取組が有効であった