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High expression of Fas-associated factor 1 indicates a poor prognosis in non-small-cell lung cancer
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Fas-associated factor 1 (FAF1) is a death-promoting protein identified as an interaction partner of the death receptor Fas. The downregulation and mutation of FAF1 have been reported in a variety of human tumors, but there have been few studies on lung cancer. Here, we investigated the prognostic significance of FAF1 expression in non-small-cell lung cancer (NSCLC), and whether aberrant FAF1 expression may be involved in the pathogenesis and prognosis of NSCLC. FAF1 expression was examined in NSCLC specimens as well as human lung cancer cell lines. In addition, changes in cell viability and apoptosis upon regulating FAF1 expression were investigated in lung cancer cell lines. As a result, high FAF1 expression was significantly associated with a poor prognosis in NSCLC. In lung cancer cell lines, FAF1 downregulation hindered cell viability and tended to promote early apoptosis. In conclusion, this is the first study of the clinical significance of FAF1 in NSCLC, showing that FAF1 overexpression is associated with a poor prognosis in NSCLC and that FAF1 acts as a dangerous factor rather than an apoptosis promoter in NSCLC.doctoral thesi
CLEC10A expression defines functionally distinct subsets of conventional type 2 dendritic cells (cDC2) in the mouse lung
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科doctoral thesi
In vivo illustration of altered dopaminergic and GABAergic systems in early Parkinson's disease
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Background: Changes in g-aminobutyric acid (GABA) function are noted in patients with Parkinson’s disease (PD) who have some non-motor impairments. However, dopamine-related GABA function and GABA-related cognitive changes are still unclear.
Methods: Thirteen drug-naive early-stage PD patients underwent a series of PET scans with [11C]flumazenil(FMZ) and [11C]CFT. The [11C]FMZ binding potential (BPND) derived from a Logan plot analysis was compared between PD patients and age-matched controls. The [11C]CFT radioactivity relative to the cerebellar counterpart was estimated as a semiquantitative value [11C]CFT SUVR. Correlations between [11C]FMZ BPND and [11C]CFT SUVR in the same region of interest were also examined.
Results: In patients in the PD group, [11C]CFT SUVR was significantly lower in the putamen. The levels of [11C]FMZ BPND in the cerebral cortex (frontal lobe dominancy) and
the affected-side putamen were also reduced. In addition, [11C]CFT SUVR was negatively correlated with the [11C]FMZ BPND level in the affected-side putamen. In patients in the PD group, the total frontal assessment battery (FAB) score was positively correlated with the [11C]FMZ BPND in the frontal region.
Conclusion: GABAergic dysfunction coexists with dopaminergic loss not only in the putamen but also over the extrastriatal region in patients with early PD and is related to frontal dysfunction. The negative correlation of [11C]CFT SUVR with [11C]FMZ BPND in the affected putamen suggests that a greater dopaminergic demise would decelerate GABA release (or an increase in tracer binding), resulting in persistent failure of the GABAergic system in PD patients.doctoral thesi
Multimorbidity patterns and the relation to self-rated health among older Japanese people: a nationwide cross-sectional study
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Objectives Classifying individuals into multimorbidity patterns can be useful to identify the target population with poorer clinical outcomes. Self-rated health (SRH) is one of the core outcomes in multimorbidity patients. Although studies have reported that multimorbidity is associated with poor SRH, whether certain patterns have stronger associations remains unknown. Therefore, this study aimed to identify the prevalence and patterns of multimorbidity and investigate the association between multimorbidity patterns and SRH in an older Japanese population.
Design Cross-sectional study.
Setting Data were obtained from the 2013 Comprehensive Survey of Living Conditions, a nationally representative survey of the general Japanese population.
Participants This study mainly examined 23 730 participants aged ≥65 years who were not hospitalised or institutionalised.
Primary outcome measure Poor SRH was defined as choosing ‘not very good’ or ‘bad’ from five options: ‘excellent’, ‘fairly good’, ‘average’, ‘not very good’ and ‘bad’.
Results The prevalence of multimorbidity was 40.9% and that of poor SRH was 23.8%. Three multimorbidity patterns were identified by exploratory factor analysis: (1) degenerative/mental health, (3) malignant/digestive/urological/haematological and (3) cardiovascular/metabolic. Multivariable modified Poisson regression analysis revealed that high malignant/digestive/urological/haematological, degenerative/mental health and cardiovascular/metabolic pattern scores, corresponding to the number of affected body systems in each pattern, were significantly associated with poor SRH (adjusted risk ratio (aRR)=1.68, 95% CI: 1.60 to 1.76; aRR=1.63, 95% CI: 1.58 to 1.69; and aRR=1.31, 95% CI: 1.26 to 1.36, respectively). When including the Kessler 6 score, a screening scale for psychological distress, in the analysis, the association between each multimorbidity pattern score and poor SRH decreased.
Conclusions Malignant/digestive/urological/ haematological and degenerative/mental health patterns may be associated with a high risk for poor SRH. Further research should focus on interventions to improve SRH in multimorbidity patients.doctoral thesi
A neonatal case of acute human parechovirus type 3 encephalopathy with being pathogen identified by the meningitis encephalitis multiplex PCR test
Get PDFヒトパレコウイルス3型（HPeV3）は，新生児期に敗血症や脳炎脳症の原因となる代表的なウイルスである．髄膜炎脳炎マルチプレックスPCRテスト（mPCR）は複数の病原体のPCRを同時に行う検査法であり，この検査の普及によりHPeVの検出例が増加している．mPCRにより同定したHPeV3による急性脳症の新生児例を報告する．症例は日齢14の新生児．日齢12に発熱し，解熱後に左半身の間代発作と無呼吸発作を発症した．活気不良，LDH高値，血液凝固異常，フェリチン上昇を認めた．髄液の細胞数増多や蛋白上昇はなかった．頭部MRI拡散強調像にて，白質と脳梁に異常高信号を認めた．髄液を用いたmPCR髄膜炎・脳炎パネルにて，HPeV由来の核酸が検出され，HPeV急性脳症と診断し，免疫グロブリンの投与を行った．退院後に髄液，咽頭，血液において，HPeV3 DNA陽性が判明した．HPeV急性脳症は非特異的な症状を示すため，mPCRが早期診断に有用である．Human parechovirus-3 (HPeV3) is one of the major causes of sepsis and encephalitis/encephalopathy in neonates. A multiplex PCR meningitis/encephalitis panel can perform PCR for multiple etiologic pathogens in one time. This case was a 14-day-old girl born at full term. She had a fever on 12 days of age, and after the fever resolved, she had episode of left hemispheric seizures and apnea. Ictal electroencephalogram showed rhythmic slow-wave discharges. Her blood tests showed elevated liver enzymes, coagulation abnormalities, and elevated ferritin. Cerebrospinal fluid analysis revealed no elevated protein and pleocytosis. Diffusion weighted image of brain MRI showed hyperintensity area in white matter and corpus callosum. HPeV derived nucleic acid was detected by the multiplex PCR meningitis/encephalitis panel. We made diagnosis of HPeV encephalopathy and underwent immunoglobulin therapy. HPeV3 DNA was detected in her blood, pharynx, cerebrospinal fluid after discharge from the hospital. Because symptoms caused by HPeV infection are nonspecific, the multiplex PCR meningitis/encephalitis panel is useful for early diagnosis.journal articl
Family pharmacy and medication adherence among older adults in Japan: A cross-sectional study of JAGES 2019.
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Neural substrates of cough control during coughing
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科Cough is known as a protective reflex to keep the airway free from harmful substances. Although brain activity during cough was previously examined mainly by functional magnetic resonance imaging (fMRI) with model analysis, this method does not capture real brain activity during cough. To obtain accurate measurements of brain activity during cough, we conducted whole-brain scans during different coughing tasks while correcting for head motion using a restraint-free positron emission tomography (PET) system. Twenty-four healthy right-handed males underwent multiple PET scans with [15 O]H2O. Four tasks were performed during scans: “resting”; “voluntary cough (VC)”, which simply repeated spontaneous coughing; “induced cough (IC)”, where participants coughed in response to an acid stimulus in the cough‐inducing method with tartaric acid (CiTA); and “suppressed cough (SC)”, where coughing was suppressed against CiTA. The whole brain analyses of motion-corrected data revealed that VC chiefly activated the cerebellum extending to pons. In contrast, CiTA-related tasks (IC and SC) activated the higher sensory regions of the cerebral cortex and associated brain regions. The present results suggest that brain activity during simple cough is controlled chiefly by infratentorial areas, whereas manipulating cough predominantly requires the higher sensory brain regions to allow top-down control of information from the periphery.doctoral thesi