胎児マクロファージはEMTを誘導して破水した羊膜の治癒を促進する

京都大学新制・課程博士博士(医学)甲第24790号医博第4982号新制||医||1066(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 竹内 理, 教授 斎藤 通紀, 教授 生田 宏一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Investigation on oblique shock waves occurred in the supersonic carbon dioxide two-phase flow

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.In the refrigeration systems using the two-phase flow ejector, it is important to understand expansion waves and shock waves which are generated at the outlet of the nozzle. The theoretical oblique shock wave relations are derived for extreme conditions. Numerical analysis of the oblique twophase flow is also presented. Two types of two dimensional convergent-divergent nozzles with and without the inclined wall are used to measure pressure profiles along the nozzles wall. The two-phase flow in the divergent section of the nozzle obviously exhibits the supersonic decompression behavior. Numerical results can represent the experimental results with fairly good precision, but the reflections of the oblique shock wave cannot be predicted. The diameter of the droplet in twophase flow in the nozzle is guessed by this experiment to be the order of 5 [μm] and momentum frozen phenomenon occurs in this situation. The experimental oblique shock wave has the particular character of the two-phase flow, which is never seen in single phase flow explained by gas dynamics. The observation of the present study reveals the intrinsic feature that appears only in the supersonic two-phase flow.dc201

Transvenous embolisation via an occluded inferior petrosal sinus for cavernous sinus dural arteriovenous fistulas

Aim of the study: We retrospectively searched for cases of transvenous embolisation for cavernous sinus dural arteriovenous fistulas.Materials and methods: Twenty-five cases underwent transvenous embolisation via the inferior petrosal sinus (IPS). IPS was probed using a standard 0.035-inch guidewire for microcatheter navigation, which was successful in all cases.Results: IPS was occluded in 17 cases (68%). Only one case experienced a complication, where the approach was changed to the contralateral side because of internal jugular vein injury. The relationship between the external auditory canal and the IPS route was reviewed in 18 cases using digital angiography (lateral view). The guidewire passed across, above, or below the external auditory canal in 10 (56%), six (33%), and two (11%) cases, respectively.Clinical implications: No previous reports have analysed the relationship between the external auditory canal and the IPS route. We present a safe and successful technique for approaching the cavernous sinus via the IPS

Klinički i patološki nalazi kod pojave Tyzzerove bolesti u kunića u Hrvatskoj

Clinical and pathological findings found during an outbreak of Tyzzer’s disease in a rabbit colony in Croatia are described in this paper. The disease occurred in young rabbits, approximately 50 days old. Over a period of six months, 148 weaned rabbits from a total group of 1753 weaned animals died with symptoms of severe gastrointestinal disease. The main clinical signs observed were diarrhea, abdominal distension, anorexia, weight loss and apathy. Five weaned rabbits were examined at the Department of Pathology of Veterinary Faculty. In all necropsied animals severe entero-hepatic lesions were seen characterized by disseminated hepatic focal necroses and transmural necrotic typhlitis. Only one animal had necrotic myocarditis. For histopathology the tissue blocks were sectioned in 5μm thick sections and stained using HE, PAS, GMS and the Giemsa method. Immunohistochemistry using anti-Clostridium piliforme RT and MSK strains reacted positively within the hepatocytes and intestine. Polymerase chain reaction (PCR) assay (liver and caecum) amplified the 196-bp DNA fragment specifi c to 16S ribosomal RNA of C. piliforme. This is the first confirmed and described case of Tyzzer’s disease in rabbits in Croatia.U radu su opisani klinički i patološki nalazi Tyzzerove bolesti u jednom uzgoju kunića u Hrvatskoj. Bolest se pojavila u mladih kunića prosječne dobi od 50 dana. U razdoblju od 6 mjeseci uginulo je 148 odbijenih kunića od ukupno 1753 životinje sa znakovima jake gastrointestinalne bolesti. Glavni su klinički znaci bili proljev, proširenje trbuha, anoreksija, gubitak težine i apatija. U Zavodu za opću patologiju i patološku morfologiju Veterinarskoga fakulteta bilo je pregledano pet životinja. Na razudbi su u svih životinja utvrđene jake enterohepatične lezije karakterizirane diseminiranim fokalnim nekrozama po jetrima i nekrotičnom upalom cijele stijenke slijepoga crijeva. U jedne životinje je utvrđen i nekrotični miokarditis. Za patohistološku pretragu uklopljena tkiva rezana su u rezove debljine 5 μm i bojena HE, PAS, GMS i Giemsa metodom. Imunohistokemijska reakcija pri upotrebi anti-RT i anti-MSK sojeva antiseruma protiv Clostridium piliforme bila je pozitivna unutar hepatocita i crijeva (Dr. S. Kawamura, Laboratory of Biomedical Science, Dept. of Veterinary Medical Science, University of Tokyo). PCR je pokazao amplifikaciju 196-bp DNA fragmenta specifičnoga za 16S ribosomsku RNA bakterije C. piliforme. Ovo je prvi potvrđeni i opisani slučaj Tyzzerove bolesti u kunića u Hrvatskoj

Oseltamivir Prescription and Regulatory Actions Vis-à-Vis Abnormal Behavior Risk in Japan: Drug Utilization Study Using a Nationwide Pharmacy Database

BACKGROUND: In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting. METHODOLOY/PRINICPAL FINDINGS: In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases). The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases). CONCLUSIONS/SIGNIFICANCE: The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question the validity of the current discrimination by age and agent (Abstract translation is available in Japanese: Appendix S1)

HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis

白血病を引き起こすタンパク質間相互作用の発見. 京都大学プレスリリース. 2021-08-31.Leukemic oncoproteins cause uncontrolled self-renewal of hematopoietic progenitors by aberrant gene activation, eventually causing leukemia. However, the molecular mechanism underlying aberrant gene activation remains elusive. Here, we showed that leukemic MLL fusion proteins associate with the HBO1 histone acetyltransferase (HAT) complex through their trithorax homology domain 2 (THD2) in various human cell lines. MLL proteins associated with the HBO1 complex through multiple contacts mediated mainly by the ING4/5 and PHF16 subunits in a chromatin-bound context where histone H3 lysine 4 tri-methylation marks were present. Of the many MLL fusions, MLL-ELL particularly depended on the THD2-mediated association with the HBO1 complex for leukemic transformation. The C-terminal portion of ELL provided a binding platform for multiple factors including AF4, EAF1, and p53. MLL-ELL activated gene expression in murine hematopoietic progenitors by loading an AF4/ENL/P-TEFb (AEP) complex onto the target promoters wherein the HBO1 complex promoted the association with AEP complex over EAF1 and p53. Moreover, the NUP98-HBO1 fusion protein exerted its oncogenic properties via interaction with MLL but not its intrinsic HAT activity. Thus, the interaction between the HBO1 complex and MLL is an important nexus in leukemic transformation, which may serve as a therapeutic target for drug development

Three-dimensional human placenta-like bud synthesized from induced pluripotent stem cells

Placental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology

Evolution of the primate glutamate taste sensor from a nucleotide sensor

霊長類におけるグルタミン酸の旨味の起源 --体の大きな霊長類は旨味感覚で葉の苦さを克服--. 京都大学プレスリリース. 2021-08-30.Taste perception plays an essential role in food selection. Umami (savory) tastes are sensed by a taste receptor complex, T1R1/T1R3, that detects proteinogenic amino acids. High sensitivity to l-glutamate (l-Glu) is a characteristic of human T1R1/T1R3, but the T1R1/T1R3 of other vertebrates does not consistently show this l-Glu response. Here, we demonstrate that the l-Glu sensitivity of T1R1/T1R3 is a derived state that has evolved repeatedly in large primates that rely on leaves as protein sources, after their divergence from insectivorous ancestors. Receptor expression experiments show that common amino acid substitutions at ligand binding sites that render T1R1/T1R3 sensitive to l-Glu occur independently at least three times in primate evolution. Meanwhile T1R1/T1R3 senses 5′-ribonucleotides as opposed to l-Glu in several mammalian species, including insectivorous primates. Our chemical analysis reveal that l-Glu is one of the major free amino acids in primate diets and that insects, but not leaves, contain large amounts of free 5′-ribonucleotides. Altering the ligand-binding preference of T1R1/T1R3 from 5′-ribonucleotides to l-Glu might promote leaf consumption, overcoming bitter and aversive tastes. Altogether, our results provide insight into the foraging ecology of a diverse mammalian radiation and help reveal how evolution of sensory genes facilitates invasion of new ecological niches