Control of rat glomerular microcirculation by juxtaglomerular adenosine A1 receptors

Control of rat glomerular microcirculation by juxtaglomerular adenosine A1 receptors. The role of adenosine A1 receptors in the glomerular microcirculation and tubuloglomerular feedback (TGF) was studied in anesthetized Sprague-Dawley rats. TGF activity was assessed as the reduction in proximal tubular stop-flow pressure (SFP) on establishing orthograde perfusion of the loop of Henle with artificial tubular fluid at 40 nl/min. Administration of a selective A1 receptor antagonist, KW-3902 (0.5 μg/kg/min i.v.), increased fractional excretion of Na (FENa) 4.3-fold without changing blood pressure, glomerular filtration rate, renal plasma flow, or filtration fraction. SFP in the absence of distal flow (SFP0) increased, and TGF-mediated SFP reduction was suppressed dose dependently [by 23 ± 2% from an SFP0 of 34 ± 1mm Hg, by 15 ± 4% from 36 ± 2mm Hg, and by 2 ± 1% from 39 ± 1mm Hg during vehicle, low- and high-dose infusions (0.5 and 5.0 μg/kg/min), respectively]. Intratubular or peritubular capillary administration of 10-4m KW-3902 completely suppressed TGF without affecting SFP0. TGF suppression and elevation of SFP0 during systemic A1 blockade indicated vasodilation, both in the afferent arteriole and more proximal preglomerular vessels. Inhibition of tubular Na reabsorption combined with TGF suppression allowed the marked natriuresis. TGF suppression through systemic, luminal, and peritubular application of the drug suggest that juxtaglomerular apparatus A1 receptors are important in the control of glomerular microcirculation

心房性ナトリウム利尿ペプチドの尿細管糸球体フィードバックに及ぼす効果

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1060号, 学位授与年月日：平成1年6月21日,学位授与年：198

SDSSp J104433.04−-012502.2 at z=5.74z=5.74 is Gravitationally Magnified by an Intervening Galaxy

During the course of our optical deep survey program on L$\alpha$ emitters at $z \approx 5.7$ in the sky area surrounding the quasar SDSSp J104433.04$-$012502.2 at $z=5.74$, we found that a faint galaxy with $m_B$(AB) $\approx 25$ is located at \timeform{1".9} southwest of the quasar. Its broad-band color properties from $B$ to $z^\prime$ suggest that the galaxy is located at a redshift of $z \sim 1.5$ -- 2.5. This is consistent with no strong emission line in our optical spectroscopy. Since the counter image of the quasar cannot be seen in our deep optical images, the magnification factor seems not to be very high. Our modest estimate is that this quasar is gravitationally magnified by a factor of 2.Comment: 11 pages, 5 figures, PASJ, in pres

Boron Compounds for Neutron Capture Therapy in the Treatment of Brain Tumors

Boron neutron capture therapy (BNCT), which uses the capture reaction between neutrons and boron-10, an isotope of boron, is rapidly gaining interest. The reason for this is the successful development of a compact accelerator-type neutron generator that can be installed in a hospital and launched into the clinical setting. BNCT, which provides selective radiotherapeutic effects at the cellular level, is expected to be effective against invasive cancer. We have been investigating BNCT applications in various types of malignant brain tumors, especially malignant gliomas, as medical applications. Recently, we have conducted clinical trials using the developed accelerator neutron source. Research on pharmaceutical applications of compounds that transport boron to cancer cells is expected to be in even greater need. Currently, the only boron agent used in cancer therapy is BPA (Borofaran 10B), which takes advantage of the demand for essential amino acids, but the research and development of boron agents are an absolutely key technology to further improve the precision of this treatment modality. This chapter summarizes and discusses the results of BNCT in the treatment of brain tumors

Biomarker discovery for practice of precision medicine in hypopharyngeal cancer: a theranostic study on response prediction of the key therapeutic agents

Background: Hypopharyngeal cancer is a relatively rare malignancy with poor prognosis. Current chemotherapeutic algorithm is still far from personalized medicine, and the identification of the truly active therapeutic biomarkers and/or targets is eagerly awaited.Methods: Venturing to focus on the conventional key chemotherapeutic drugs, we identified the most correlative genes (and/or proteins) with cellular sensitivity to docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-FU) in the expression levels, through 3 steps approach: genome-wide screening, confirmation study on the quantified expression levels, and knock-down and transfection analyses of the candidates. The probable action pathways of selected genes were examined by Ingenuity Pathway Analysis using a large-scale database, The Cancer Genome Atlas.Results: The first genome-wide screening study derived 16 highly correlative genes with cellular drug sensitivity in 15 cell lines (|R| > 0.8, P 0.5, P Conclusion: We newly propose 4 molecules -AGR2, PDE4D,NINJ2 and CDC25B) as the powerful exploratory markers for prediction of cellular response to 3 key chemotherapeutic drugs in hypopharyngeal cancers and also suggest their potentials to be the therapeutic targets, which could contribute to the development of precision medicine of the essential chemotherapy in hypopharyngeal patients.</p

Roles of PsbI and PsbM in photosystem II dimer formation and stability studied by deletion mutagenesis and X-ray crystallography

PsbM and PsbI are two low molecular weight subunits of photosystem II (PSII), with PsbM being located in the center, and PsbI in the periphery, of the PSII dimer. In order to study the functions of these two subunits from a structural point of view, we crystallized and analyzed the crystal structure of PSII dimers from two mutants lacking either PsbM or PsbI. Our results confirmed the location of these two subunits in the current crystal structure, as well as their absence in the respective mutants. The relative contents of PSII dimers were found to be decreased in both mutants, with a concomitant increase in the amount of PSII monomers, suggesting a destabilization of PSII dimers in both of the mutants. On the other hand, the accumulation level of the overall PSII complexes in the two mutants was similar to that in the wild-type strain. Treatment of purified PSII dimers with lauryldimethylamine N-oxide at an elevated temperature preferentially disintegrated the dimers from the PsbM deletion mutant into monomers and CP43-less monomers, whereas no significant degradation of the dimers was observed from the PsbI deletion mutant. These results indicate that although both PsbM and PsbI are required for the efficient formation and stability of PSII dimers in vivo, they have different roles, namely, PsbM is required directly for the formation of dimers and its absence led to the instability of the dimers accumulated. On the other hand, PsbI is required in the assembly process of PSII dimers in vivo; once the dimers are formed, PsbI was no longer required for its stability

Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo