Abnormalities of the First Three Steps of Gait Initiation in Patients with Parkinson's Disease with Freezing of Gait

The purpose of this study was to investigate abnormalities of the first three steps of gait initiation in patients with Parkinson's disease (PD) with freezing of gait (FOG). Ten PD patients with FOG and 10 age-matched healthy controls performed self-generated gait initiation. The center of pressure (COP), heel contact positions, and spatiotemporal parameters were estimated from the vertical pressures on the surface of the force platform. The initial swing side of gait initiation was consistent among the trials in healthy controls but not among the trials in PD patients. The COP and the heel contact position deviated to the initial swing side during the first step, and the COP passed medial to each heel contact position during the first two steps in PD patients. Medial deviation of the COP from the first heel contact position had significant correlation with FOG questionnaire item 5. These findings indicate that weight shifting between the legs is abnormal and that medial deviation of the COP from the first heel contact position sensitively reflects the severity of FOG during the first three steps of gait initiation in PD patients with FOG

Identification and characterization of factors involved in the tumorigenicity of cancer stem cells

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 宮島 篤, 東京大学教授 秋山 徹, 東京大学教授 濡木 理, 東京大学教授 白髭 克彦, 東京大学教授 多羽田 哲也University of Tokyo(東京大学

Is Presence or History of Extracolonic Primary Malignancy a Risk for Colorectal Neoplasia? An Analysis of Patients Who Underwent Colonoscopy

Whether presence or history of extracolonic primary malignancy is a risk for colorectal neoplasia is not fully known. In this study, 26,452 first-time colonoscopy cases were examined using a colonoscopy database. Among the analyzed subjects, 3,026 (11%) subjects had history or concomitance of extracolonic primary malignancy, while the remaining 23,426 subjects did not. Colorectal neoplasia was observed in 39% of all the subjects. A crude comparison showed that the prevalence of any type of colorectal neoplasia was higher in subjects with extracolonic malignancy than in those without (42% vs. 39%, p＝0.0012). However, after adjusting for confounding factors, the odds ratios (ORs) of subjects with extracolonic malignancy for having colorectal neoplasia, advanced neoplasia, and cancer were all less than 1.0, and all significantly different from those of subjects without extracolonic malignancy. Analysis according to the type of extracolonic malignancy revealed that gastric cancer cases had a significantly lower risk for colorectal advanced neoplasia (OR:0.81;95% CI:0.67-0.99). Among major malignancies, only esophageal squamous cell cancer cases had increased risk for colorectal neoplasia (OR:1.66;95% CI:1.20-2.29). Patients with presence or history of extracolonic malignancy did not carry a higher risk of occurrence of colorectal neoplasia

Multicentric extra-abdominal desmoid tumors arising in bilateral lower limbs

Extra-abdominal desmoid tumors preferentially affect the shoulders, arms, backs, buttocks, and thighs of young adults. Multicentric occurrence is rather rare but seems to be another distinctive feature of extra-abdominal desmoid tumors. In this article we report a rare case of multicentric extra-abdominal desmoid tumors arising in bilateral lower limbs

Protective Effects of GLP-1 on Glomerular Endothelium and Its Inhibition by PKCβ Activation in Diabetes

To characterize glucagon-like peptide (GLP)-1 signaling and its effect on renal endothelial dysfunction and glomerulopathy. We studied the expression and signaling of GLP-1 receptor (GLP-1R) on glomerular endothelial cells and the novel finding of protein kinase A–dependent phosphorylation of c-Raf at Ser259 and its inhibition of angiotensin II (Ang II) phospho–c-Raf(Ser338) and Erk1/2 phosphorylation. Mice overexpressing protein kinase C (PKC)β2 in endothelial cells (EC-PKCβ2Tg) were established. Ang II and GLP-1 actions in glomerular endothelial cells were analyzed with small interfering RNA of GLP-1R. PKCβ isoform activation induced by diabetes decreased GLP-1R expression and protective action on the renal endothelium by increasing its degradation via ubiquitination and enhancing phospho–c-Raf(Ser338) and Ang II activation of phospho-Erk1/2. EC-PKCβ2Tg mice exhibited decreased GLP-1R expression and increased phospho–c-Raf(Ser338), leading to enhanced effects of Ang II. Diabetic EC-PKCβ2Tg mice exhibited greater loss of endothelial GLP-1R expression and exendin-4–protective actions and exhibited more albuminuria and mesangial expansion than diabetic controls. These results showed that the renal protective effects of GLP-1 were mediated via the inhibition of Ang II actions on cRaf(Ser259) and diminished by diabetes because of PKCβ activation and the increased degradation of GLP-1R in the glomerular endothelial cells

Detection of the Onset of Ischemia and Carcinogenesis by Hypoxia-Inducible Transcription Factor-Based In Vivo Bioluminescence Imaging

An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential

回腸利用膀胱拡大術後に膀胱腺癌を発症した一例

京都府立医科大学附属北部医療センター泌尿器科Department of Urology, North Medical Center Kyoto Prefectural University of Medicine小腸癌は全消化管疾患の中でも稀な疾患である。また、回腸利用膀胱拡大術後に利用した回腸から腺癌を生じた報告も稀であり、その治療法は確立されていない。若年時に先天性二分脊椎による神経因性膀胱に対する回腸利用膀胱拡大術後に63 歳時に回腸膀胱吻合部に腺癌を生じた一例を経験した。経尿道的手術、免疫チェックポイント阻害薬など試みるも効果得られず、診断から約１２ヶ月後永眠された。若干の文献的考察を加え報告する

内分泌・外照射併用密封小線源療法(Tri-modality)が有用であったT4N1前立腺癌の1例

京都府立医科大学附属北部医療センター　泌尿器科福知山市民病院　放射線科Department of Urology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Radiology, Fukuchiyama City Hospital転移性前立腺癌に対する治療は従来、内分泌治療が適応とされていた。しかし近年、転移性前立腺癌に対しても局所治療が有用であるとの報告が散見されるようになった。今回我々はT4N1M0前立腺癌に対して、密封小線源療法(BT:Brachytherapy)に体外放射線照射療法(EBRT:External Beam Radiotherapy)、アンドロゲン除去療法(ADT:Androgen Deprivation Therapy)を加えたTri-modality治療を行い良好な成績を得た症例を経験したため、若干の文献的考察を加え報告する。(著者抄録

Structure and properties of densified silica glass: characterizing the order within disorder

世界一構造秩序のあるガラスの合成と構造解析に成功 --ガラスの一見無秩序な構造の中に潜む秩序を抽出--. 京都大学プレスリリース. 2021-12-25.The broken symmetry in the atomic-scale ordering of glassy versus crystalline solids leads to a daunting challenge to provide suitable metrics for describing the order within disorder, especially on length scales beyond the nearest neighbor that are characterized by rich structural complexity. Here, we address this challenge for silica, a canonical network-forming glass, by using hot versus cold compression to (i) systematically increase the structural ordering after densification and (ii) prepare two glasses with the same high-density but contrasting structures. The structure was measured by high-energy X-ray and neutron diffraction, and atomistic models were generated that reproduce the experimental results. The vibrational and thermodynamic properties of the glasses were probed by using inelastic neutron scattering and calorimetry, respectively. Traditional measures of amorphous structures show relatively subtle changes upon compacting the glass. The method of persistent homology identifies, however, distinct features in the network topology that change as the initially open structure of the glass is collapsed. The results for the same high-density glasses show that the nature of structural disorder does impact the heat capacity and boson peak in the low-frequency dynamical spectra. Densification is discussed in terms of the loss of locally favored tetrahedral structures comprising oxygen-decorated SiSi4 tetrahedra