微小物体可視化センサLSIの設計

金沢大学大学院自然科学研究科情報システム金沢大学工学

Carcinogen-induced Thyroid Proliferative Lesions in Wistar Hannover GALAS Rats with Thyroid Dysplasia

Incidences and morphological features of thyroid proliferative lesions induced by carcinogens in Wistar Hannover GALAS rats (GALAS rats) showing normal growth with or without thyroid dysplasia were examined. All thyroid tissue samples were obtained from our recently conducted study using male GALAS rats treated with 5 carcinogens according to the medium-term multiorgan carcinogenicity bioassay protocol (called DMBDD treatment). In the DMBDD-treated rats, thyroid dysplasia was found in 9 out of 114 rats. Follicular cell adenomas were found in 5 out of 9 rats with thyroid dysplasia and in 7 out of 105 rats without thyroid dysplasia. The incidence of adenoma was significantly increased in rats with thyroid dysplasia (55.6%) compared with that in rats without thyroid dysplasia (6.7%). Adenomas in rats with thyroid dysplasia were observed as single or multiple nodules, well demarcated and composed of variously sized vacuolated cells or unvacuolated cells. These histopathological features and staining profiles of luminal colloid for PAS and thyroglobulin, together with PCNA-positive cells, were fundamentally similar to those of rats without thyroid dysplasia. On the other hand, the luminal colloid in adenomas of rats with thyroid dysplasia had a tendency to be poorly stained for T4 compared with that of rats without thyroid dysplasia. From these findings, it appears that dysplastic thyroids of rats showing normal growth are more sensitive to carcinogens than normal thyroids. In addition, the morphological features of carcinogen-induced thyroid proliferative lesions in GALAS rats with thyroid dysplasia were fundamentally similar to those of rats without thyroid dysplasia, except for the vacuoles and T4 staining profile

Simultaneous Validation of Seven Physical Activity Questionnaires Used in Japanese Cohorts for Estimating Energy Expenditure: A Doubly Labeled Water Study

Background: Physical activity questionnaires (PAQs) used in large-scale Japanese cohorts have rarely been simultaneously validated against the gold standard doubly labeled water (DLW) method. This study examined the validity of seven PAQs used in Japan for estimating energy expenditure against the DLW method.Methods: Twenty healthy Japanese adults (9 men; mean age, 32.4 [standard deviation {SD}, 9.4] years, mainly researchers and students) participated in this study. Fifteen-day daily total energy expenditure (TEE) and basal metabolic rate (BMR) were measured using the DLW method and a metabolic chamber, respectively. Activity energy expenditure (AEE) was calculated as TEE − BMR − 0.1 × TEE. Seven PAQs were self-administered to estimate TEE and AEE.Results: The mean measured values of TEE and AEE were 2,294 (SD, 318) kcal/day and 721 (SD, 161) kcal/day, respectively. All of the PAQs indicated moderate-to-strong correlations with the DLW method in TEE (rho = 0.57–0.84). Two PAQs (Japan Public Health Center Study [JPHC]-PAQ Short and JPHC-PAQ Long) showed significant equivalence in TEE and moderate intra-class correlation coefficients (ICC). None of the PAQs showed significantly equivalent AEE estimates, with differences ranging from −547 to 77 kcal/day. Correlations and ICCs in AEE were mostly weak or fair (rho = 0.02–0.54, and ICC = 0.00–0.44). Only JPHC-PAQ Short provided significant and fair agreement with the DLW method.Conclusions: TEE estimated by the PAQs showed moderate or strong correlations with the results of DLW. Two PAQs showed equivalent TEE and moderate agreement. None of the PAQs showed equivalent AEE estimation to the gold standard, with weak-to-fair correlations and agreements. Further studies with larger sample sizes are needed to confirm these findings

Accuracy of 12 Wearable Devices for Estimating Physical Activity Energy Expenditure Using a Metabolic Chamber and the Doubly Labeled Water Method: Validation Study

Background: Self-monitoring using certain types of pedometers and accelerometers has been reported to be effective for promoting and maintaining physical activity (PA). However, the validity of estimating the level of PA or PA energy expenditure (PAEE) for general consumers using wearable devices has not been sufficiently established.Objective: We examined the validity of 12 wearable devices for determining PAEE during 1 standardized day in a metabolic chamber and 15 free-living days using the doubly labeled water (DLW) method.Methods: A total of 19 healthy adults aged 21 to 50 years (9 men and 10 women) participated in this study. They followed a standardized PA protocol in a metabolic chamber for an entire day while simultaneously wearing 12 wearable devices: 5 devices on the waist, 5 on the wrist, and 2 placed in the pocket. In addition, they spent their daily lives wearing 12 wearable devices under free-living conditions while being subjected to the DLW method for 15 days. The PAEE criterion was calculated by subtracting the basal metabolic rate measured by the metabolic chamber and 0.1×total energy expenditure (TEE) from TEE. The TEE was obtained by the metabolic chamber and DLW methods. The PAEE values of wearable devices were also extracted or calculated from each mobile phone app or website. The Dunnett test and Pearson and Spearman correlation coefficients were used to examine the variables estimated by wearable devices.Results: On the standardized day, the PAEE estimated using the metabolic chamber (PAEEcha) was 528.8±149.4 kcal/day. The PAEEs of all devices except the TANITA AM-160 (513.8±135.0 kcal/day; P>.05), SUZUKEN Lifecorder EX (519.3±89.3 kcal/day; P>.05), and Panasonic Actimarker (545.9±141.7 kcal/day; P>.05) were significantly different from the PAEEcha. None of the devices was correlated with PAEEcha according to both Pearson (r=−.13 to .37) and Spearman (ρ=−.25 to .46) correlation tests. During the 15 free-living days, the PAEE estimated by DLW (PAEEdlw) was 728.0±162.7 kcal/day. PAEE values of all devices except the Omron Active style Pro (716.2±159.0 kcal/day; P>.05) and Omron CaloriScan (707.5±172.7 kcal/day; P>.05) were significantly underestimated. Only 2 devices, the Omron Active style Pro (r=.46; P=.045) and Panasonic Actimarker (r=.48; P=.04), had significant positive correlations with PAEEdlw according to Pearson tests. In addition, 3 devices, the TANITA AM-160 (ρ=.50; P=.03), Omron CaloriScan (ρ=.48; P=.04), and Omron Active style Pro (ρ=.48; P=.04), could be ranked in PAEEdlw.Conclusions: Most wearable devices do not provide comparable PAEE estimates when using gold standard methods during 1 standardized day or 15 free-living days. Continuous development and evaluations of these wearable devices are needed for better estimations of PAEE

Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use

Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study

Human neural stem cells (hNSCs) transplantation in several brain injury models has established their therapeutic potential. However, the feasibility of hNSCs transplantation is still not clear for acute subdural hematoma (ASDH) brain injury that needs external decompression. Thus, the aim of this pilot study was to test feasibility using a rat ASDH decompression model with two clinically relevant transplantation methods. Two different methods, in situ stereotactic injection and hNSC-embedded matrix seating on the brain surface, were attempted. Athymic rats were randomized to uninjured or ASDH groups (F344/NJcl-rnu/rnu, n = 7–10/group). Animals in injury group were subjected to ASDH, and received decompressive craniectomy and 1-week after decompression surgery were transplanted with green fluorescent protein (GFP)-transduced hNSCs using one of two approaches. Histopathological examinations at 4 and 8 weeks showed that the GFP-positive hNSCs survived in injured brain tissue, extended neurite-like projections resembling neural dendrites. The in situ transplantation group had greater engraftment of hNSCs than matrix embedding approach. Immunohistochemistry with doublecortin, NeuN, and GFAP at 8 weeks after transplantation showed that transplanted hNSCs remained as immature neurons and did not differentiate toward to glial cell lines. Motor function was assessed with rotarod, compared to control group (n = 10). The latency to fall from the rotarod in hNSC in situ transplanted rats was significantly higher than in control rats (median, 113 s in hNSC vs. 69 s in control, P = 0.02). This study first demonstrates the robust engraftment of in situ transplanted hNSCs in a clinically-relevant ASDH decompression rat model. Further preclinical studies with longer study duration are warranted to verify the effectiveness of hNSC transplantation in amelioration of TBI induced deficits

Requirement of Interaction between Mast Cells and Skin Dendritic Cells to Establish Contact Hypersensitivity

The role of mast cells (MCs) in contact hypersensitivity (CHS) remains controversial. This is due in part to the use of the MC-deficient Kit W/Wv mouse model, since Kit W/Wv mice congenitally lack other types of cells as a result of a point mutation in c-kit. A recent study indicated that the intronic enhancer (IE) for Il4 gene transcription is essential for MCs but not in other cell types. The aim of this study is to re-evaluate the roles of MCs in CHS using mice in which MCs can be conditionally and specifically depleted. Transgenic Mas-TRECK mice in which MCs are depleted conditionally were newly generated using cell-type specific gene regulation by IE. Using this mouse, CHS and FITC-induced cutaneous DC migration were analyzed. Chemotaxis assay and cytoplasmic Ca2+ imaging were performed by co-culture of bone marrow-derived MCs (BMMCs) and bone marrow-derived dendritic cells (BMDCs). In Mas-TRECK mice, CHS was attenuated when MCs were depleted during the sensitization phase. In addition, both maturation and migration of skin DCs were abrogated by MC depletion. Consistently, BMMCs enhanced maturation and chemotaxis of BMDC in ICAM-1 and TNF-α dependent manners Furthermore, stimulated BMDCs increased intracellular Ca2+ of MC upon direct interaction and up-regulated membrane-bound TNF-α on BMMCs. These results suggest that MCs enhance DC functions by interacting with DCs in the skin to establish the sensitization phase of CHS