肝臓におけるNO産生とその調節機構の解析

生後3週齢のラット新生子の肝臓においてNO産生の亢進が認められ，このNO産生はeNOS Ser^1176のリン酸化により調節され，産生されたNOは肝細胞の増殖を維持していることが示唆された。Hepatocytes have high ability to proliferate and are still undifferentiated in neonates. During development, the rat liver at 3 weeks after birth has been reported as the late maturation stage, increasing the number of the differentiated hepatocytes. Nitric oxide (NO) has been reported as a key mediator to enhance the hepatocyte proliferation in regenerating liver. However it is unclear that whether NO contributes to the hepatocyte proliferation in neonatal rat. We performed a semi-quantitative evaluation of endogenous NO production using a spin trap followed by electron paramagnetic resonance (EPR) spectroscopy with Fe-N, N-diethyldithiocarbamate (Fe-DETC) complex as a NO-trapping reagent in the rat liver during development. The NO production in the liver was increased at 3 weeks after birth and then declined. Administration of the NO synthase (NOS) inhibitor L-NAME suppressed the endogenous NO production and the hepatocyte proliferation in the rat liver at 3 weeks after birth. The phosphorylation level of NOS3 at Ser1177, the activating residue of the enzyme, was increased at 3 weeks after birth and then declined as well as the NO production pattern. These results suggest that NO is mainly synthesized by NOS3 up-regulated by phosphorylation at Ser1177 and enhances the hepatocyte proliferation in the rat liver at 3 weeks after birth. These findings provide a novel insight into the contribution of NO to hepatic growth and the liver maturation during development

動物生命科学領域の教育設備の充実

動物生命科学領域の基盤的な実習については，系統的な機器備品が質量ともに整備されつつあることから，より充実した少人数での実習環境が整いつつある

Ectopic Varices Rupture in the Gastroduodenal Anastomosis Successfully Treated with N-butyl-2-cyanoacrylate Injection

The term &#34;ectopic varices&#34; is used to describe dilated portosystemic collateral veins in unusual locations other than the gastroesophageal region. We recently experienced a rare case of ectopic varices that developed in the gastroduodenal anastomosis after subtotal gastrectomy. A 70-year-old male with liver cirrhosis due to hepatitis C virus infection was admitted for hematemesis and tarry stool. He had received a subtotal gastrectomy with the Billroth-I method for gastric ulcer at 46 years of age. Although emergency endoscopy revealed esophageal and gastric fundal varices, there were no obvious bleeding points. After removal of the coagula, ectopic varices and a fibrin plug were observed on the gastroduodenal anastomosis. During the observation, blood began to spurt from the fibrin plug. N-butyl-2-cyanoacrylate with lipiodol injection succeeded in hemostasis. Splenic angiography showed gastric varices feeding from a short gastric vein and the posterior gastric vein. The blood flow around the bleeding point, as indicated by lipiodol deposition, had decreased, and no feeding vein was observed. Endoscopic and angiographic findings are shown and the treatment for such lesions is discussed.</p

Controlling oxygen coordination and valence of network forming cations

Understanding the structure-property relationship of glass material is still challenging due to a lack of periodicity in disordered materials. Here, we report the properties and atomic structure of vanadium phosphate glasses characterized by reverse Monte Carlo modelling based on neutron/synchrotron X-ray diffraction and EXAFS data, supplemented by Raman and NMR spectroscopy. In vanadium-rich glass, the water durability, thermal stability and hardness improve as the amount of P2O5 increases, and the network former of the glass changes from VOx polyhedra to the interplay between VOx polyhedra and PO4 tetrahedra. We find for the first time that the coordination number of oxygen atoms around a V4+ is four, which is an unusually small coordination number, and plays an important role for water durability, thermal stability and hardness. Furthermore, we show that the similarity between glass and crystal beyond the nearest neighbour distance is important for glass properties. These results demonstrate that controlling the oxygen coordination and valence of the network-forming cation is necessary for designing the properties of glass

胎盤における一酸化窒素（NO）の産生とNO合成酵素（NOS）の発現

Nitric oxide (NO) production in the rat placenta(pars fetalis placentae and decidua basalis) was monitored and quantified by electron paramagnetic resonance (EPR) spectroscopy using an iron complex with N-(dithiocarboxy) sarcosine (Fe-DTCS) as a NO trapping reagent. The expression of nitric oxide synthase (NOS) isoforms was also examined by quantitative reverse transcriptase-mediated polymerase chain reaction (RT-PCR) analysis. The EPR spectrum of the placenta with Fe-DTCS trapping showed a triplet signal (g = 2.038) derived from an NO-Fe-DTCS complex. The heights of the NO-Fe-DTCS (a) and MnO (b) signals were simultaneously measured to calculate the ratio (a/b) of these signal heights used for the quantification of the NO production level. Although, the ratio of the signal heights of NO-Fe-DTCS and MnO did not vary significantly with gestational stage in the fetal placenta, the ratio was markedly decreased in the maternal placenta during the last few days of gestation. At the gestational stages examined, the level of NOS 2 (iNOS) mRNA expression was significantly higher than that of NOS 3 (eNOS) mRNA expression at any given stage in the fetal placenta, and the production pattern of NO was in good accordance with the expression pattern of NOS 2 in the maternal placenta. These results suggest that NOS 2 is the predominant producer of NO in the placenta and that NOS 2-generated NO plays significant roles in the maintenance of placental functions immediately before birth

Nucleotide Polymorphisms in the Canine Noggin Gene and Their Distribution Among Dog (Canis lupus familiaris) Breeds

Noggin (NOG) is an important regulator for the signaling of bone morphogenetic proteins. In this study, we sequenced the complete coding sequence of the canine NOG gene and characterized the nucleotide polymorphisms. The sequence length varied from 717 to 729 bp, depending on the number of a 6-bp tandem repeat unit (GGCGCG), an insertion that has not been observed in other mammalian NOG genes investigated to date. It results in extensions of (Gly–Ala)3–5 in the putative NOG protein. To survey the distribution of these tandem repeat polymorphisms, we analyzed 126 individuals in seven dog breeds. We identified only three alleles: (GGCGCG)3, (GGCGCG)4, and (GGCGCG)5. Although the allele frequencies were remarkably different among the breeds, the three alleles were present in all seven of the breeds and did not show any deviation from Hardy–Weinberg equilibrium

Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans

Rare hematopoietic stem and progenitor cell (HSPC) pools outside the bone marrow (BM) contribute to blood production in stress and disease but remain ill-defined. Although non-mobilized peripheral blood (PB) is routinely sampled for clinical management, the diagnosis and monitoring potential of PB HSPCs remains untapped, as no healthy PB HSPC baseline has been reported. Here we comprehensively delineate human extramedullary HSPC compartments comparing spleen, PB and mobilized PB (mPB) to BM using single-cell RNA-seq and/or functional assays. We uncover HSPC features shared by extramedullary tissues and others unique to PB. First, in contrast to actively dividing BM HSPCs, we find no evidence of substantial ongoing hematopoiesis in extramedullary tissues at steady state, but report increased splenic HSPC proliferative output during stress erythropoiesis. Second, extramedullary stem cells/multipotent progenitors (HSC/MPPs) from spleen, PB and mPB share a common transcriptional signature and increased abundance of lineage-primed subsets compared to BM. Third, healthy PB HSPCs display a unique bias towards erythroid-megakaryocytic differentiation. At HSC/MPP level, this is functionally imparted by a subset of phenotypic CD71+ HSC/MPPs, exclusively producing erythrocytes and megakaryocytes, highly abundant in PB but rare in other adult tissues. Finally, the unique erythroid-megakaryocytic-skewing of PB is perturbed with age, in essential thrombocythemia and in beta-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are non-proliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction

Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans.

Rare hematopoietic stem and progenitor cell (HSPC) pools outside the bone marrow (BM) contribute to blood production in stress and disease but remain ill-defined. Although nonmobilized peripheral blood (PB) is routinely sampled for clinical management, the diagnosis and monitoring potential of PB HSPCs remain untapped, as no healthy PB HSPC baseline has been reported. Here we comprehensively delineate human extramedullary HSPC compartments comparing spleen, PB, and mobilized PB to BM using single-cell RNA-sequencing and/or functional assays. We uncovered HSPC features shared by extramedullary tissues and others unique to PB. First, in contrast to actively dividing BM HSPCs, we found no evidence of substantial ongoing hematopoiesis in extramedullary tissues at steady state but report increased splenic HSPC proliferative output during stress erythropoiesis. Second, extramedullary hematopoietic stem cells/multipotent progenitors (HSCs/MPPs) from spleen, PB, and mobilized PB share a common transcriptional signature and increased abundance of lineage-primed subsets compared with BM. Third, healthy PB HSPCs display a unique bias toward erythroid-megakaryocytic differentiation. At the HSC/MPP level, this is functionally imparted by a subset of phenotypic CD71+ HSCs/MPPs, exclusively producing erythrocytes and megakaryocytes, highly abundant in PB but rare in other adult tissues. Finally, the unique erythroid-megakaryocytic-skewing of PB is perturbed with age in essential thrombocythemia and β-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are nonproliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction

EGUIDE project and treatment guidelines

Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1‐day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self‐completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders