チイキ デ ハタラク イシ ノ ゲンジョウ ト テイゲン

Nowadays, there is a shortage of doctors working in rural areas in Japan. Because the elderly population has increased rapidly in rural areas, more community-based primary care physicians are needed in future. This review is to clarify motivation of a doctor working in a rural area in Tokushima prefecture. I showed my carrier （called Dr. H） and community in Tokushima prefecture. Dr. H, now in his fifties, was born at the same town as the hospital now working. Dr. H graduated the University of Tokushima, and practiced internal medicine and medical research in the Tokushima University, its related hospitals, and National Cancer Center （Tsukiji, Tokyo）. But in his forties, Dr. H started working at rural clinics and small hospitals. Through clinical practices, Dr. H presented 10 posters at the Semiannual Meetings of the Tokushima Medical Association during 10 years. In Tokushima prefecture, three big issues were discovered and invented : a new disease called as “Japanese spotted fever”, blue light-emitting diode （LED） and “Awa Odori exercise”. Even in rural small hospitals, it is meaningful to practice medicine and research. Every doctor must have this “research mind” even in the rural areas

Stimulus-Dependent State Transition between Synchronized Oscillation and Randomly Repetitive Burst in a Model Cerebellar Granular Layer

Information processing of the cerebellar granular layer composed of granule and Golgi cells is regarded as an important first step toward the cerebellar computation. Our previous theoretical studies have shown that granule cells can exhibit random alternation between burst and silent modes, which provides a basis of population representation of the passage-of-time (POT) from the onset of external input stimuli. On the other hand, another computational study has reported that granule cells can exhibit synchronized oscillation of activity, as consistent with observed oscillation in local field potential recorded from the granular layer while animals keep still. Here we have a question of whether an identical network model can explain these distinct dynamics. In the present study, we carried out computer simulations based on a spiking network model of the granular layer varying two parameters: the strength of a current injected to granule cells and the concentration of Mg2+ which controls the conductance of NMDA channels assumed on the Golgi cell dendrites. The simulations showed that cells in the granular layer can switch activity states between synchronized oscillation and random burst-silent alternation depending on the two parameters. For higher Mg2+ concentration and a weaker injected current, granule and Golgi cells elicited spikes synchronously (synchronized oscillation state). In contrast, for lower Mg2+ concentration and a stronger injected current, those cells showed the random burst-silent alternation (POT-representing state). It is suggested that NMDA channels on the Golgi cell dendrites play an important role for determining how the granular layer works in response to external input

ノウソッチュウ ノ イリョウ レンケイ : ケンナンブ イリョウ ノ カイゼン オ メザシテ

Background : Cerebrovasucular disease have been known as“brain attack”since introduction of the treatment with recombinant tissue plasminogen activator against cerebral infarction. Emergent transport of apoplexy patients to hospitals with stroke care unit is needed. But nowadays, shortage of doctors appeared in Kaifu county of Tokushima Prefecture. Objectives : The aim of this study was to clarify problems on patients with apoplexy in this district. Methods : Three representative clinical cases are presented. Results : They were suffered from acute cerebral infarction, subarachnoid hemorrhage, or chronic cerebral infarction complicated with aspiration pneumonia and bed-sores. Conclusions : In order to treat patients with cerebrovasucular diseases effectively in this district, organic and friendly co-operation among doctors of stroke care units, physicians belonging to the Tokushima Medical Association, and staffs of the geriatric health service facilities is needed

地域で生活している５５歳以上の方の慢性疾患，年齢の捉え方，睡眠の質，健康関連QOL，日常生活行動との関係性

Japan’s aging population rate is increasing and healthy life expectancy has decreases by 10 years shorter than average life expectancy. The aim of this study is to determine the relationship among chronic disease, sleep quality, health-related quality of life (HRQOL), and activities of daily living in people over 55 years old who live in the community. Subjects were 161 persons aged 57 to 90 years who were treated with chronic disease in the outpatient department of the A hospital. Exclusion criteria included patients with dementia, cancer and severe heart disease. The survey evaluation questionnaires included the Pittsburgh Sleep Quality Index (PSQI), HRQOL by Short-Form 8 Health Survey (SF-8), and activities of daily living. Variables associated with quality of sleep, HRQOL in univariate analysis with p < 0.05 were entered into multivariate analysis using logistic regression with a stepwise forward selection procedure to determine independent variables and their association with major causes. The logistic regression analysis was done using SPSS software and the post-hoc power of the study was estimated using G*power. The level of significance was set at p < 0.05. The risk factor of poor sleep quality was because of history of cancer [odds ratio (OR): 3.53, 95% confidence interval (CI): 1.06 - 11.77], and insomnia (OR: 3.25, 95% CI: 1.55 - 6.79). The risk factors of poor physical HRQOL were motor disease (OR: 2.62, 95% CI: 1.36 - 5.07), respiratory disease (OR: 3.24, 95% CI: 1.27 - 8.26) and having pain (OR: 11.71, 95% CI: 5.35 - 25.66). In addition, anemia was found to be a risk factor of poor mental HRQOL (OR: 4.87, 95% CI: 1.11 - 21.33). The feeling-for-their-body-age (OR: 0.30, 95% CI: 0.15-0.59) was as “younger than actual age” and advanced the risk factor of poor sleep quality. In addition, feeling-for-their-age (OR: 0.44, 95% CI: 0.21 - 0.92) resulted in reduced risk factor of poor physical HRQOL. The risk factor of poor sleep quality was due to a patient with history of cancer. The factor for good sleep quality and the good factor for physical HRQOL were indications of feeling younger than the actual age

地域で生活している５５歳以上の方の慢性疾患，年齢の捉え方，睡眠の質，健康関連QOL，日常生活行動との関係性

Japan’s aging population rate is increasing and healthy life expectancy has decreases by 10 years shorter than average life expectancy. The aim of this study is to determine the relationship among chronic disease, sleep quality, health-related quality of life (HRQOL), and activities of daily living in people over 55 years old who live in the community. Subjects were 161 persons aged 57 to 90 years who were treated with chronic disease in the outpatient department of the A hospital. Exclusion criteria included patients with dementia, cancer and severe heart disease. The survey evaluation questionnaires included the Pittsburgh Sleep Quality Index (PSQI), HRQOL by Short-Form 8 Health Survey (SF-8), and activities of daily living. Variables associated with quality of sleep, HRQOL in univariate analysis with p < 0.05 were entered into multivariate analysis using logistic regression with a stepwise forward selection procedure to determine independent variables and their association with major causes. The logistic regression analysis was done using SPSS software and the post-hoc power of the study was estimated using G*power. The level of significance was set at p < 0.05. The risk factor of poor sleep quality was because of history of cancer [odds ratio (OR): 3.53, 95% confidence interval (CI): 1.06 - 11.77], and insomnia (OR: 3.25, 95% CI: 1.55 - 6.79). The risk factors of poor physical HRQOL were motor disease (OR: 2.62, 95% CI: 1.36 - 5.07), respiratory disease (OR: 3.24, 95% CI: 1.27 - 8.26) and having pain (OR: 11.71, 95% CI: 5.35 - 25.66). In addition, anemia was found to be a risk factor of poor mental HRQOL (OR: 4.87, 95% CI: 1.11 - 21.33). The feeling-for-their-body-age (OR: 0.30, 95% CI: 0.15-0.59) was as “younger than actual age” and advanced the risk factor of poor sleep quality. In addition, feeling-for-their-age (OR: 0.44, 95% CI: 0.21 - 0.92) resulted in reduced risk factor of poor physical HRQOL. The risk factor of poor sleep quality was due to a patient with history of cancer. The factor for good sleep quality and the good factor for physical HRQOL were indications of feeling younger than the actual age

Heparin cofactor II reduces albuminuria

Aims/Introduction: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs). Recent data have shown that PARs influence the development of glomerular diseases including diabetic kidney disease (DKD) by regulating inflammation. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with DKD development, as represented by albuminuria. Materials and Methods: Plasma HCII activity and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP), were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 310 Japanese patients with diabetes mellitus (176 males and 134 females). The relationships between plasma HCII activities and those DKD urine biomarkers were statistically evaluated. In addition, the relationship between plasma HCII activities and annual uACR changes was statistically evaluated for 201/310 patients (115 males and 86 females). Results: The mean plasma HCII activity of all participants was 93.8 ± 17.7%. Multivariate-regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log-transformed uACR values (P = 0.036 and P = 0.006, respectively) but not uL-FABPCR (P = 0.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log-transformed uACR increments after adjusting for confounding factors (P = 0.001 and P = 0.014, respectively). Conclusions: The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria

Heparin Cofactor II and NAFLD in T2DM

Aims: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs), and thrombin-induced activation of PARs promotes the development of non-alcoholic fatty liver disease (NAFLD). Since heparin cofactor II (HCII) specifically inactivates thrombin action, we hypothesized that plasma HCII activity correlates with the severity of NAFLD. Methods: A cross-sectional study was conducted. Plasma HCII activity and noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined in 305 Japanese patients with type 2 diabetes mellitus (T2DM). The relationships between plasma HCII activity and the clinical markers were statistically evaluated. Results: Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p＜0.001), NFS (p＜0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012). Conclusions: Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM

自然発生黒色腫担癌豚の選択的熱中性子捕捉療法 : 線量分布と局所反応の検討

前臨床実験として自然発生黒色腫担癌豚に10B-BPA(10B-Para-boronophenylalanine)を用いた選択的熱中性子捕捉療法を施行し,その時の局所,全身の中性子およびγ線の線量分布を調べたので局所反応とともに報告する.熱中性子源として武蔵工業大学原子炉研究所の原子炉を用いた.10B-BPA 15.8g(200mg/kg)を経静脈的に投与し,100kw,210分間の熱中性子照射を行った.腫瘍部以外を遮蔽するために,bismuth面より順にLiFシート,LiFタイル,鉛ブロックを配置した.上記collimation systemにより腫瘍周辺組織の熱中性子線量を腫瘍部の約1/100に減弱させることができ,また全身被曝線量軽減の意味からも効果を認めた.また,局所反応においても,ビラン,潰瘍等を伴わず治療傾向を示した.We carried out pre-clinical experiment for treatment of spontaneously occurring melanoma using 10B-Para-boronophenylalanine (10B-BPA) and also measured actual dose distribution of neutron and γ-ray irradiation on melanoma itself, surrounding normal tissue and distant body surfaces. As the source of the thermal neutron beam, we used Musashi Institute of Technology Reactor for Medical Purposes. An hour prior to thermal neutron irradiation of 100kw for 210 minutes, 15.8g of 10B-BPA (200mg/kg) was administered to the pig then the pig was undertaken general anesthesia which was remotely maintained and set in irradiation in front of the bismuth surface of the reactor. LiF tiles, LiF sheets and lead blocks were arranged as the collimator for shielding the pig skin but for the melanoma lesion. The neutron fluence to tumor surrounding normal skin was about one hundredth of that to melanoma and this collimation system was so effective that further decrease in neutron fluence and γ-ray to distant body surface were attained. As the result of this experiment, the pig melanoma showed complete disappearance and the lesion was covered by normal skin without erosive and ulcerative changes

A Computational Mechanism for Unified Gain and Timing Control in the Cerebellum

Precise gain and timing control is the goal of cerebellar motor learning. Because the basic neural circuitry of the cerebellum is homogeneous throughout the cerebellar cortex, a single computational mechanism may be used for simultaneous gain and timing control. Although many computational models of the cerebellum have been proposed for either gain or timing control, few models have aimed to unify them. In this paper, we hypothesize that gain and timing control can be unified by learning of the complete waveform of the desired movement profile instructed by climbing fiber signals. To justify our hypothesis, we adopted a large-scale spiking network model of the cerebellum, which was originally developed for cerebellar timing mechanisms to explain the experimental data of Pavlovian delay eyeblink conditioning, to the gain adaptation of optokinetic response (OKR) eye movements. By conducting large-scale computer simulations, we could reproduce some features of OKR adaptation, such as the learning-related change of simple spike firing of model Purkinje cells and vestibular nuclear neurons, simulated gain increase, and frequency-dependent gain increase. These results suggest that the cerebellum may use a single computational mechanism to control gain and timing simultaneously