Dipeptidyl peptidase-4阻害薬によるシスプラチン急性腎障害の改善効果の検討

学位の種別:課程博士University of Tokyo(東京大学

Multiple Myeloma and Kidney Disease

Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis

movement self-screening scores and pain

Background : Various musculoskeletal screening and functional performance tests are used to evaluate physical condition. However, validated analysis tools that can identify gaps in pain knowledge during athletes’ daily training are lacking. This study aimed to investigate the relationship between pain intensity in athletes during their daily training and the KOJI AWARENESS™ test in order to determine whether body dysfunction is related to pain among athletes. Methods : This cross-sectional study was conducted in a fitness center at the authors’ affiliated institution. Thirty-five athletes (17 women and 18 men) aged 20-40 years were selected for study participation. KOJI AWARENESS™ self-evaluated test scores and pain intensity during daily training, as assessed on the numerical rating scale (NRS), were recorded. Results : The KOJI AWARENESS™ score showed a strong negative correlation with the NRS score for pain intensity during daily training (r = −0.640, P < 0.001). There was a significant negative correlation between KOJI AWARENESS™ and NRS scores, even when body mass index, sex, and age were entered as control variables. Conclusions : KOJI AWARENESS™ was highly accurate in detecting pain in athletes during their training

Effectiveness of KOJI AWARENESS tool

Background : The KOJI AWARENESS™ screening test is a self-administered screening tool for assessment of mobility, stability, and strength. It provides corrective exercises corresponding to the individual’s answers to the KOJI AWARENESS™ test questions. However, there is no evidence of the effectiveness of corrective exercises in improving KOJI AWARENESS™ screening test scores and activity-related pain. Methods : Twenty- six healthy subjects (11 female and 15 male ; age 20–50 years) were selected for participation. In a controlled laboratory setting, subjects were administered the KOJI AWARENESS™ test and were provided with individualized exercise programs based on the results of this first test. KOJI AWARENESS™ results were checked on the first day immediately after the first exercise session, and then again after the two-week program. Pain intensity was also assessed during daily training using a numerical rating scale. Results : Compared to pre-intervention, KOJI AWARENESS™ scores were significantly higher immediately after the first corrective exercise session and after 2 weeks of intervention (p < 0.001). Moreover, pain intensity was significantly lower after 2 weeks of intervention (p < 0.001). Conclusions : Individualized KOJI AWARENESS™ corrective exercises were effective immediately on the first day and also after the two-week program in improving the KOJI AWARENESS™ score and reducing pain intensity during daily training

Common Hepatic Branch of Vagus Nerve-Dependent Expression of Immediate Early Genes in the Mouse Brain by Intraportal L-Arginine: Comparison with Cholecystokinin-8

Information from the peripheral organs is thought to be transmitted to the brain by humoral factors and neurons such as afferent vagal or spinal nerves. The common hepatic branch of the vagus (CHBV) is one of the main vagus nerve branches, and consists of heterogeneous neuronal fibers that innervate multiple peripheral organs such as the bile duct, portal vein, paraganglia, and gastroduodenal tract. Although, previous studies suggested that the CHBV has a pivotal role in transmitting information on the status of the liver to the brain, the details of its central projections remain unknown. The purpose of the present study was to investigate the brain regions activated by the CHBV. For this purpose, we injected L-arginine or anorexia-associated peptide cholecystokinin-8 (CCK), which are known to increase CHBV electrical activity, into the portal vein of transgenic Arc-dVenus mice expressing the fluorescent protein Venus under control of the activity-regulated cytoskeleton-associated protein (Arc) promotor. The brain slices were prepared from these mice and the number of Venus positive cells in the slices was counted. After that, c-Fos expression in these slices was analyzed by immunohistochemistry using the avidin-biotin-peroxidase complex method. Intraportal administration of L-arginine increased the number of Venus positive or c-Fos positive cells in the insular cortex. This action of L-arginine was not observed in CHBV-vagotomized Arc-dVenus mice. In contrast, intraportal administration of CCK did not increase the number of c-Fos positive or Venus positive cells in the insular cortex. Intraportal CCK induced c-Fos expression in the dorsomedial hypothalamus, while intraportal L-arginine did not. This action of CCK was abolished by CHBV vagotomy. Intraportal L-arginine reduced, while intraportal CCK increased, the number of c-Fos positive cells in the nucleus tractus solitarii in a CHBV-dependent manner. The present results suggest that the CHBV can activate different brain regions depending on the nature of the peripheral stimulus

Development of the photomultiplier tube readout system for the first Large-Sized Telescope of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is the next generation ground-based very high energy gamma-ray observatory. The Large-Sized Telescope (LST) of CTA targets 20 GeV -- 1 TeV gamma rays and has 1855 photomultiplier tubes (PMTs) installed in the focal plane camera. With the 23 m mirror dish, the night sky background (NSB) rate amounts to several hundreds MHz per pixel. In order to record clean images of gamma-ray showers with minimal NSB contamination, a fast sampling of the signal waveform is required so that the signal integration time can be as short as the Cherenkov light flash duration (a few ns). We have developed a readout board which samples waveforms of seven PMTs per board at a GHz rate. Since a GHz FADC has a high power consumption, leading to large heat dissipation, we adopted the analog memory ASIC "DRS4". The sampler has 1024 capacitors per channel and can sample the waveform at a GHz rate. Four channels of a chip are cascaded to obtain deeper sampling depth with 4096 capacitors. After a trigger is generated in a mezzanine on the board, the waveform stored in the capacitor array is subsequently digitized with a low speed (33 MHz) ADC and transferred via the FPGA-based Gigabit Ethernet to a data acquisition system. Both a low power consumption (2.64 W per channel) and high speed sampling with a bandwidth of $>$300 MHz have been achieved. In addition, in order to increase the dynamic range of the readout we adopted a two gain system achieving from 0.2 up to 2000 photoelectrons in total. We finalized the board design for the first LST and proceeded to mass production. Performance of produced boards are being checked with a series of quality control (QC) tests. We report the readout board specifications and QC results.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Sound to Language: Different Cortical Processing for First and Second Languages in Elementary School Children as Revealed by a Large-Scale Study Using fNIRS

A large-scale study of 484 elementary school children (6–10 years) performing word repetition tasks in their native language (L1-Japanese) and a second language (L2-English) was conducted using functional near-infrared spectroscopy. Three factors presumably associated with cortical activation, language (L1/L2), word frequency (high/low), and hemisphere (left/right), were investigated. L1 words elicited significantly greater brain activation than L2 words, regardless of semantic knowledge, particularly in the superior/middle temporal and inferior parietal regions (angular/supramarginal gyri). The greater L1-elicited activation in these regions suggests that they are phonological loci, reflecting processes tuned to the phonology of the native language, while phonologically unfamiliar L2 words were processed like nonword auditory stimuli. The activation was bilateral in the auditory and superior/middle temporal regions. Hemispheric asymmetry was observed in the inferior frontal region (right dominant), and in the inferior parietal region with interactions: low-frequency words elicited more right-hemispheric activation (particularly in the supramarginal gyrus), while high-frequency words elicited more left-hemispheric activation (particularly in the angular gyrus). The present results reveal the strong involvement of a bilateral language network in children’s brains depending more on right-hemispheric processing while acquiring unfamiliar/low-frequency words. A right-to-left shift in laterality should occur in the inferior parietal region, as lexical knowledge increases irrespective of language