Drug transporters mediate the uptake and elimination of drugs in various organs; therefore, having knowledge of how a transporter functions in the body would play a key role in ensuring drug efficacy in in vivo systems. In this context, we designed and synthesized [(11)C]dehydropravastatin, a novel PET probe that would be potentially useful for evaluation of the functions of the OATP1B1 and MRP2 transporters, based on the use of palladium(0)-mediated rapid C-[(11)C]methylation (viz., the rapid cross-coupling between [(11)C]methyl iodide and a boron intermediate).

Neuronal nitric oxide synthase (nNOS) is an important regulatory enzyme in the central nervous system catalyzing the production of NO, which regulates multiple biological processes in the central nervous system. However, the mechanisms by which nNOS activity is regulated are not completely understood. In the present study, the effects of protein kinases on the phosphorylation of nNOS in GH3 rat pituitary tumor cells were evaluated. We show that phosphorylation of nNOS at Ser1412 could be induced by the phosphatidylinositol 3-kinase/protein kinase B (Akt/PKB) agonist insulin, the calcium/calmodulin-dependent protein kinase II (CaM-K II) agonist A23187 or the cAMP-dependent protein kinase A (PKA) agonist IBMX, respectively. The phosphorylation levels of nNOS at Ser1412, induced by activation of Akt/PKB or CaM-K II, but not by PKA signaling, were reduced by pre-treatment with the NO donor diethylamine-NONOate. This inhibitory effect could be reversed by addition of a reducing reagent, dithiothreitol. Furthermore, the levels of phosphorylation of nNOS at Ser1412, induced by Akt/PKB or CaM-K II but not by PKA signaling, were enhanced by inhibition of nNOS activity with 7-nitroindazole. These findings suggest that the activation of nNOS can be catalyzed by at least three protein kinases, Akt/PKB, CaM-K II or PKA. NO generated from nNOS feedback prevents the activation of nNOS by inhibiting either Akt/PKB or CaM-K II but not PKA signaling.

The kana pick-out test has been widely used in Japan to evaluate the ability to divide attention in both adult and pediatric patients. However, the neural substrates underlying the ability to divide attention using the kana pick-out test, which requires participants to pick out individual letters (vowels) in a story while also reading for comprehension, thus requiring simultaneous allocation of attention to both activities, are still unclear. Moreover, outside of the clinical area, neuroimaging studies focused on the mechanisms of divided attention during complex story comprehension are rare. Thus, the purpose of the present study, to clarify the neural substrates of kana pick-out test, improves our current understanding of the basic neural mechanisms of dual task performance in verbal memory function. We compared patterns of activation in the brain obtained during performance of the individual tasks of vowel identification and story comprehension, to levels of activation when participants performed the two tasks simultaneously during the kana pick-out test. We found that activations of the left dorsal inferior frontal gyrus and superior parietal lobule increase in functional connectivity to a greater extent during the dual task condition compared to the two single task conditions. In contrast, activations of the left fusiform gyrus and middle temporal gyrus, which are significantly involved in picking out letters and complex sentences during story comprehension, respectively, were reduced in the dual task condition compared to during the two single task conditions. These results suggest that increased activations of the dorsal inferior frontal gyrus and superior parietal lobule during dual task performance may be associated with the capacity for attentional resources, and reduced activations of the left fusiform gyrus and middle temporal gyrus may reflect the difficulty of concurrent processing of the two tasks. In addition, the increase in synchronization between the left dorsal inferior frontal gyrus and superior parietal lobule in the dual task condition may induce effective communication between these brain regions and contribute to more attentional processing than in the single task condition, due to greater and more complex demands on voluntary attentional resources.

BACKGROUND Bronchiolitis obliterans (BO) is a major cause of morbidity and mortality after lung transplantation. BO is pathologically characterized by neovascularized fibro-obliteration of the allograft airway. A recent study has shown that aberrant angiogenesis during fibro-obliteration contributes to the pathogenesis of BO. Vasohibin-1 (VASH1) has been isolated as a vascular endothelial growth factor-inducible gene in endothelial cells (ECs) that inhibits migration and proliferation of ECs and exhibits anti-angiogenic activity in vivo. PURPOSE This study examines whether VASH1 inhibits fibro-obliteration of the allograft in a murine intrapulmonary tracheal transplantation model. METHOD Tracheal allografts of BALB/c mouse were transplanted into the left lung of recipient C57BL/6J mouse. We performed gene transfer to the recipient lungs using an adenovirus vector encoding human VASH1 (Ad-VASH1) or beta- garactosidase (Ad-LacZ) as the control. Tracheal allografts were harvested and pathological on days 21 and 28. RESULT Ad-VASH1 treatment reduced the vascular area on day 21 (4.6% versus 13.0%, P =.037) and day 28 (5.4% versus 13.4%, P =.022) compared with the control group. This was accompanied by significantly inhibited luminal obliteration of the tracheal allografts in the animals transferred with Ad-VASH1 compared with the control (69% versus 93%, P =.028) on day 21. We were not able to observe this effect on day 28 (92% versus 97%, P =.48). CONCLUSION Transgene expression of VASH1 in the recipient lung significantly attenuated luminal obliteration of the tracheal allograft; this was associated with significantly reduced aberrant angiogenesis in the fibro-obliterative tissue in a murine model intrapulmonary tracheal transplantation.

This study assessed the effects of soy protein isolate (SPI) on severe kidney damage in deoxycorticosterone acetate (DOCA)-salt-treated obese Zucker rats. These rats underwent heminephrectomy and were fed either casein or SPI diet for 12 weeks. From weeks 8 to 10 of the experiment, kidney damage was induced by biweekly injection of 25 mg/kg DOCA and administration of 0.5% NaCl (w/v) ad libitum. Urinary protein and N-acetyl-β-D-glucosaminidase excretions of SPI rats were much lower than those of Casein rats at weeks 1 (p < 0.01) and 2 (p < 0.05) after DOCA treatment. Abnormal mineral excretions induced by DOCA treatment in Casein rats were hardly detected in SPI rats. Severe atrophy of tubular epithelium and some flattened/detached renal tubules were also observed in Casein rats, but not in SPI rats. These results indicate that consecutive treatment of SPI protects against renal dysfunction, particularly tubulointerstitial nephritis, in DOCA-salt-treated obese Zucker rats.

ABSTRACT: A new wiping device for detecting removable contamination was developed. A cylindrical plastic scintillator (PS) is applied to a roller device. A wiping material wraps around the cylindrical PS roller, and then the roller is used for wiping to detect removable contamination (PS method). After contamination on the floor is wiped off using the roller, the wrapped PS is removed from the roller and placed in a glass vial for use in a liquid scintillation counter (LSC). The vial is measured by LSC without liquid scintillation cocktail. When the PS method was used by wrapping with NUC-Wipe™, the wiping efficiencies, except for the measurement efficiencies, were almost 15% for H and 40% for C. Also a repositionable tape (Double Stick Tape™) could be used for wiping material. The device has three main advantages: 1) Though the wiping efficiency is not very high when using the PS method, the variability observed is lower than that for hand wiping; 2) even when it is contaminated with nuclides whose maximum beta ray energies (Emax) are very close, for example C (Emax; 156 keV) and S (Emax; 167 keV), the contaminated radioisotopes are identified with their spectra by using PS; and 3) the PS method is environmentally friendly, as post-processing time is vastly shortened because it does not use a liquid scintillator. Some issues that were previously considered unavoidable in the wiping method were improved using a plastic scintillator as a roller.

Fatigue is a common complaint in modern society. As photosensitivity is associated with fatigue, this study aimed to clarify the relationship between neural response to visual stimuli and fatigue using a 160-channel whole-head-type magnetoencephalographic system. Twelve healthy male volunteers were enrolled. Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform acute fatigue-inducing mental task sessions, i.e., 0-back or 2-back test for 30min. Visual evoked magnetic field (VEF) intensities were evaluated by standardized low-resolution brain electromagnetic tomography modified for a quantifiable method. VEF consisted of two phases, and although acute fatigue did not alter the VEF intensities and the intensities before the acute fatigue-inducing mental task sessions were not correlated with the Chalder's Fatigue Scale scores in either of the two phases, the intensities after the 0-back test trials for 30min in Phase 1 and those after the 2-back test trials in Phase 2 were significantly correlated with the fatigue scale scores. The daily level of fatigue was related to VEF intensity after the acute mental fatigue loads. Our findings provide new perspectives to evaluate our daily level of fatigue as well as to clarify the neural mechanisms underlying it.

We report the observation of two narrow structures in the mass spectra of the π^{±}Υ(nS)(n=1, 2, 3) and π^{±}h_{b}(mP)(m=1, 2) pairs that are produced in association with a single charged pion in Υ(5S) decays. The measured masses and widths of the two structures averaged over the five final states are M_{1}=(10 607.2±2.0)  MeV/c^{2}, Γ_{1}=(18.4±2.4)  MeV, and M_{2}=(10 652.2±1.5)  MeV/c^{2}, Γ_{2}=(11.5±2.2)  MeV. The results are obtained with a 121.4  fb^{-1} data sample collected with the Belle detector in the vicinity of the Υ(5S) resonance at the KEKB asymmetric-energy e^{+}e^{-} collider.

Fatigue is a common problem in modern society. We attempted to identify moderate- to long-term fatigue-related alterations in the central nervous system using cognitive tasks and electroencephalography (EEG) measures. The study group consisted of 17 healthy male participants. After saliva samples were collected to measure copy number of human herpesvirus (HHV)-6 DNA to assess the level of moderate- to long-term fatigue, subjects were evaluated using EEG, with their eyes open for 2 min, then closed for 1 min sitting quietly. Thereafter, they completed cognitive task trials to evaluate simple selective attention for 3 min (Task 1) and conflict-controlling selective attention for 6 min (Task 2, which included Stroop trials). The percent error of Task 2 for Stroop trials was positively associated with the copy number of saliva HHV-6 DNA, although the simple selective attention measures in Task 1 did not differ significantly. EEG power densities (especially the alpha power density) during the eye-closed condition were negatively associated with the saliva HHV-6 DNA level. Impaired high-level information processing such as that required for conflict-controlling selective attention in the central nervous system may be a characteristic feature of moderate- to long-term fatigue.

TSH receptor antibody (TRAb) is clinically classified into thyroid stimulating antibody (TSAb) and thyroid-stimulation blocking antibody (TSBAb). Although the former is considered to cause Graves' disease (GD), its activity does not necessarily reflect hormone production and goiter size. Moreover, uptake of 99mTcO4(-), the best indicator for GD, is correlated with activity of TSH binding inhibitor immunoglobulin better than activity of TSAb. Because uptake of 99mTcO4(-) reflects thyroid volume, these observations suggest that there exist TRAb with thyrocyte growth stimulating activity (GSA) other than TSAb. In this study, we analyzed GSA of monoclonal TRAb established from patients with GD or idiopathic myxedema (IME). GSA was measured as the degree of FRTL-5 cell growth stimulated by each TRAb. The signaling pathways of the cell growth were pharmacologically analyzed. The cell growth stimulated by TSH was strongly suppressed by protein kinase A (PKA) inhibitor, but was not affected by extracellular signal regulated kinase kinase (MEK) inhibitor. Although TSAb from GD stimulated the cell growth, both inhibitors suppressed it. Surprisingly, the cell growth was also induced by TSBAb from GD and was only suppressed by MEK inhibitor. TSBAb from IME did not have GSA and attenuated the cell growth stimulated by TSH. We concluded that 1; in GD, not only TSAb but some TSBAb could stimulate thyrocyte growth. 2; TSBAb might be classified with respect to their effects on thyrocyte growth; i.e., thyrocyte growth stimulating antibody and thyrocyte growth-stimulation blocking antibody.