大豆イソフラボン成分ゲニステインのムコ多糖症3A型モデルマウスにおける分子生物学的研究

取得学位：博士(薬学），学位授与番号：博甲第1022号，学位授与年月日：平成20年3月22

Synthetic Mitochondria-Targeting Peptides Incorporating α-Aminoisobutyric Acid with a Stable Amphiphilic Helix Conformation in Plant Cells

In the genetic modification of plant cells, the mitochondrion is an important target in addition to the nucleus and plastid. However, gene delivery into the mitochondria of plant cells has yet to be established by conventional methods, such as particle bombardment, because of the small size and high mobility of mitochondria. To develop an efficient mitochondria-targeting signal (MTS) that functions in plant cells, we designed the artificial peptide (LURL)₃ and its analogues, which periodically feature hydrophobic α-aminoisobutyric acid (Aib, U) and cationic arginine (R), considering the consensus motif recognized by the mitochondrial import receptor Tom20. Circular dichroism measurements and molecular dynamics simulation studies revealed that (LURL)₃ had a propensity to form a stable α-helix in 0.1 M phosphate buffer solution containing 1.0 wt % sodium dodecyl sulfate. After internalization into plant cells via particle bombardment, (LURL)₃ revealed highly selective accumulation in the mitochondria, whereas its analogue (LARL)₃ was predominantly located in the vacuoles in addition to mitochondria. The high selectivity of (LURL)₃ can be attributed to the incorporation of Aib, which promotes the hydrophobic interaction between the MTS and Tom20 by increasing the hydrophobicity and helicity of (LURL)₃. The present study provided a prospective mitochondrial targeting system using the simple design of artificial peptides

OTUD1 deubiquitinase regulates NF-κB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways

Deubiquitinating enzymes (DUBs) regulate numerous cellular functions by removing ubiquitin modifications. We examined the effects of 88 human DUBs on linear ubiquitin chain assembly complex (LUBAC)-induced NF-κB activation, and identified OTUD1 as a potent suppressor. OTUD1 regulates the canonical NF-κB pathway by hydrolyzing K63-linked ubiquitin chains from NF-κB signaling factors, including LUBAC. OTUD1 negatively regulates the canonical NF-κB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway. Mass spectrometric analysis showed that OTUD1 binds KEAP1, and the N-terminal intrinsically disordered region of OTUD1, which contains an ETGE motif, is indispensable for the KEAP1-binding. Indeed, OTUD1 is involved in the KEAP1-mediated antioxidant response and reactive oxygen species (ROS)-induced cell death, oxeiptosis. In Otud1−/−-mice, inflammation, oxidative damage, and cell death were enhanced in inflammatory bowel disease, acute hepatitis, and sepsis models. Thus, OTUD1 is a crucial regulator for the inflammatory, innate immune, and oxidative stress responses and ROS-associated cell death pathways

Development of a broadband superluminescent diode based on self-assembled InAs quantum dots and demonstration of high-axial-resolution optical coherence tomography imaging

We developed a near-infrared (NIR) superluminescent diode (SLD) based on self-assembled InAs quantum dots (QDs) and demonstrated high-axial-resolution optical coherence tomography (OCT) imaging using this QD-based SLD (QD-SLD). The QD-SLD utilized InAs QDs with controlled emission wavelengths as a NIR broadband light emitter, and a tilted waveguide with segmented electrodes was prepared for edge-emitting broadband electroluminescence (EL) spanning approximately 1–1.3 μm. The bandwidth of the EL spectrum was increased up to 144 nm at a temperature of 25 °C controlled using a thermoelectric cooler. The inverse Fourier transform of the EL spectrum predicted a minimum resolution of 3.6 μm in air. The QD-SLD was subsequently introduced into a spectral-domain (SD)-OCT setup, and SD-OCT imaging was performed for industrial and biological test samples. The OCT images obtained using the QD-SLD showed an axial resolution of ~4 μm, which was almost the same as that predicted from the spectrum. This axial resolution is less than the typical size of a single biological cell (~5 μm), and the practical demonstration of high-axial-resolution OCT imaging shows the application of QD-SLDs as a compact OCT light source, which enables the development of a portable OCT system

Successful management of unstable angina in a ravulizumab-treated patient with paroxysmal nocturnal hemoglobinuria

Ravulizumab is an anti-C5 antibody approved for treating paroxysmal nocturnal hemoglobinuria (PNH). In August 2019, a 77-year-old Japanese man with PNH, who had been on ravulizumab treatment for 2 years, was hospitalized for chest discomfort and malaise. Electrocardiography identified a right bundle block, and elevated serum troponin I and d-dimer suggested ischemic heart disease. Cardiac catheterization revealed severe stenosis in the left anterior descending coronary artery, and intracoronary stenting relieved his chest discomfort. The final diagnosis was unstable angina unrelated to ravulizumab, and the patient's ravulizumab treatment was uninterrupted with no significant complications of PNH. This case report highlights the importance of continuing complement inhibition therapy during acute coronary events

岩手医科大学歯学部口腔病理学教室における病理組織検査の報告 : 2001年度の集計

Pathological examinations diagnosed at our department in 2001 were statistically reviewed. There were 641 examinations for 516 cases (Male: 244, Female 272). Cases were most frequent in patients in their seventh decades (106 cases). In histological classifications of the lesions (mean age ±SD), odontogenic tumors consisted of 5 ameloblastomas (40.4±25.2), 2 odontomas (20.2±8.0), and one malignant ameloblastoma (33.0). The non-oclontogenic benign lesions were 44 fibrous hyperplasias (55.2±18.9), 28 hyperkeratosis (leukoplakia) (55.7±13.4), 7 hemangiomas (65.6±5.9), 6 pleomorphic adenomas (56.7±11.5), 6 osteomas (exostosis, enostosis), 4 papillomas (80.7±7.4), 4 epithelial dysplasias (61.5±11.9) and 3 periapical cemental dysplasias (30.1±13.7). Non-odontogenic malignant tumors consisted of 53 squamous cell carcinomas (68.1±12.6) and 3 verrucous carcinomas (71.7±4.8). The odontogenic cysts consisted of 45 radicular cysts (45.2±14.3), 21 dentigerous cysts (41.4±19.9) and 8 primordial cysts (29.9±11.3). The non-odontogenic cysts consisted of 44 mucoceles (30.3±22.6), 18 postoperative maxillary cysts (56.1±11.4), 3 incisive canal cysts (54.3±9.9) and 2 dermoid cysts (16.5±2.5). In addition, 10 Sjogren syndromes (53.9±11.0), 7 lichen planus (69.1±12.9), 26 chronic localized hyperplastic gingivitis (epulis) (60.1±15.7) and 6 dental granulomas (50.5±16.9) were revealed

上顎洞および食道原発の二重癌の1剖検例

In cases of multiple primary cancers, the combination of head/neck cancer and upper digestive tract cancer is often found. However, it is extremely rare for maxillary sinus cancer and esophageal cancer to occur simultaneously. This paper reports on an autopsy case of double primary cancers of the maxillary sinus and esophagus. The patient had been suffering from carcinoma of the maxillary sinus for about 12 months but the lesion was uncontrollable. At autopsy, the following two primary carcinomas were found : one was a moderately differentiated squamous cell carcinoma originated from the maxillary sinus infiltrating into the hard palate and tongue, with metastases in several regional lymph nodes, a para-aortic lymph node and bilateral lungs. The other was a progressive, well-differentiated squamous cell carcinoma originated from the esophagus transformed mucosa with epithelial dysplasia. Furthermore, two masses of gastrointestinal mesenchymal tumors (GIMT) of the stomach were noted