Identification of sirm , a Novel Insulin-regulated SH3 Binding Protein That Associates with Grb-2 and FYN

We have previously developed a mouse model of insulin-resistant diabetes by targeted inactivation of the insulin receptor gene. During studies of gene expression in livers of insulin receptor-deficient mice, we identified a novel cDNA, which we have termed sirm (Son of Insulin Receptor Mutant mice). sirm is largely, albeit not exclusively, expressed in insulin-responsive tissues. Insulin is a potent modulator of sirm expression, and sirm mRNA levels correlate with tissue sensitivity to insulin. The product of the sirm gene is a serine/threonine-rich protein with several proline-rich motifs and an NPNY motif, conforming to the consensus sequence recognized by the phosphotyrosine binding domains of insulin receptor substrate and Shc proteins. However, Sirm bears no extended homologies with other known proteins. Based on the sequences of the proline-rich domains, we sought to determine whether Sirm binds to the SH3 domains of FYN and Grb-2. We demonstrate here that Sirm binds to FYN and Grb-2 in 3T3-L1 adipocytes and that insulin treatment results in the dissociation of the Sirm.FYN and Sirm.Grb-2 complexes. We also show that Sirm is a substrate for the kinase activity of FYN in vitro. Based on the patterns of expression of sirm, its regulation by insulin, and the interactions with molecules in the insulin signaling pathway, we surmise that Sirm plays a role in modulating tissue sensitivity to insulin

Magnetotransport Measurements of η-Mo_4O_<11> Crystals Using a Hybrid Magnet(Transport and Fermiology)

Magnetoresistance and Hall effect have been measured at 4.2 K using a hybrid magnet up to 26 T for several crystals of quasi-two-dimensional η-Mo_4O_ that has a charge-density-wave (CDW) induced nested multiple carrier band structure. The magnetoresistance is exceptionally large and the Hall resistivity shows a unique magnetic field dependence. We have confirmed the existence of characteristic hysteresis phenomena in both quantities when a field-sweep range exceeds a threshold value (?10 T). The hysteresis effects can be related with an effective and magnetic field dependent irreversible process for the CDW formation and destruction. We have also found that the hysteresis and quantum oscillations in the magnetotransport are strongly sample-dependent

Usability of detecting delivery errors during treatment of prostate VMAT with a gantry-mounted transmission detector

Volumetric‐modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector “Delta4 Discover® (D4D)” was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance‐to‐agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta4 Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A‐side and B‐side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of −0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission‐type detector “D4D” is thus suitable for detecting delivery errors during irradiation

Verifying the validity and reliability of the Japanese version of the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale

BackgroundPediatric patients, especially in the preverbal stage, cannot self-report intensity of pain therefore several validated observational tools, including the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale, have been used as a benchmark to evaluate pediatric pain. Unfortunately, this scale is currently unavailable in Japanese, precluding its widespread use in Japanese hospitals.ObjectivesTo translate and verify the validity and reliability of the Japanese version of the FLACC Behavioral Scale.MethodBack-translation was first conducted by eight medical researchers, then an available sample of patients at the University of Tsukuba Pediatric Intensive Care Unit (from May 2017 to August 2017) was enrolled in a clinical study. Two researchers evaluated the validity of the translated FLACC Behavioral Scale by weighted kappa coefficient and intraclass correlation coefficients (ICC). Observational pain was simultaneously measured by the visual analog scale (VAS obs) and reliability was evaluated by correlation analysis.ResultThe original author approved the translation. For the clinical study, a total of 121 observations were obtained from 24 pediatric patients. Agreement between observers was highly correlated for each of the FLACC categories (Face: κ = 0.85, Leg: κ = 0.74, Activity: κ = 0.89, Cry: κ = 0.93, Consolability: κ = 0.93) as well as the total score (Total: κ = 0.95,). Correlation analysis demonstrated a good criterion validation between the FLACC scale and the VAS obs. (r = 0.96)ConclusionOur Japanese version of the FLACC Behavioral Scale shows high validity and reliability

Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity

During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-ϐ-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein ϐ (C/EBPϐ) expression levels. The effect of C/EBPϐ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPϐ transgenic mice to investigate the relationship between C/EBPϐ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPϐ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPϐ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPϐ transgenic mice decreased C/EBPϐ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPϐ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure

Picosecond Time-Resolved Linear Polarization Spectroscopy of the Blue-Green Photoluminescence in Vacuum-Annealed Porous Silicon

P(論文)departmental bulletin pape

Verifying the Japanese version of the Preschool Confusion Assessment Method for the ICU (psCAM‐ICU)

AimPediatric delirium has been well investigated and its prevalence is reported to be from 20% to 44%. For pediatric intensive care settings, several validated assessment tools for diagnosing delirium, including the Preschool Confusion Assessment Method for the Intensive Care Unit (psCAM‐ICU), are available in English. However, validated assessment tools for identifying pediatric delirium are unavailable in Japanese. Therefore, the aim of this study is to verify the Japanese translation of the psCAM‐ICU.MethodsWe enrolled patients at the Pediatric ICU at University of Tsukuba Hospital (Tsukuba, Japan) from May 2017 to February 2019. Enrollment criteria included patients aged 6 months to 5 years, and we excluded coma patients scoring under −4 on the Richmond Agitation–Sedation Scale or suffering from stroke. Pediatric patient delirium was simultaneously evaluated by three medical workers (pediatric intensivist and researchers). Psychiatrists then verified these findings against criteria of the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition. We evaluated criterion validity (sensitivity and specificity) and reliability using Cohen\u27s κ coefficient.ResultsWe made a total of 56 independent assessments of 19 patients (42% female) with an average age of 18 (±15) weeks. Mechanical ventilation was used at least once in 73% of patients and the positive rate of delirium was 54% in total observation. Overall, the psCAM‐ICU showed high sensitivity, specificity (sensitivity, 0.90 [95% confidence interval [CI], 0.80–0.94]; specificity, 0.93 [95% CI, 0.83–0.97]), and high reliability within the researcher assessments (κ = 0.92; 95% CI, 0.82–1.0).ConclusionWe verified the psCAM‐ICU and it shows high validity and reliability

Ablation of TSC2 Enhances Insulin Secretion by Increasing the Number of Mitochondria through Activation of mTORC1

) mice. The present study examines the effects of TSC2 ablation on insulin secretion from pancreatic beta cells. mice and TSC2 knockdown insulin 1 (INS-1) insulinoma cells treated with small interfering ribonucleic acid were used to investigate insulin secretion, ATP content and the expression of mitochondrial genes. mice exhibit hyperinsulinemia due to an increase in the number of mitochondria as well as enlargement of individual beta cells via activation of mTORC1.Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells

Development of the Japanese version of the Intensive Care Unit Trigger Tool to detect adverse events in critically ill patients

AimThe Intensive Care Unit Trigger Tool (ICUTT) was developed to detect adverse events (AEs) in intensive care unit (ICU) patients. The purpose of this study was to determine the validity and reliability of the Japanese version of the ICUTT (ICUTT-J).MethodsThe translation of ICUTT was carried out based on the guideline for translation of instruments. Subsequently, two review teams independently reviewed 50 patients\u27 medical records using the ICUTT-J, and agreement regarding the presence and number of AEs was evaluated to ensure reliability.ResultsThe ICUTT-J was submitted to the authors of the original ICUTT, who confirmed it as being equivalent to the original version. The item-content validity index and scale-content validity index were 1.00 and 1.00, respectively. Interrater reliability showed moderate agreement of κ = 0.52 in terms of the presence of AEs and linear weighting of κ = 0.49 (95% confidence interval, 0.28, 0.71) in terms of the number of AEs.ConclusionThis study\u27s findings suggest that the ICUTT-J is valid and moderately reliable for use in ICUs