前立腺癌に対するPepleomycin(Bleomycin Derivative, NK-631)の効果

未治療の前立腺腺癌2症例に本剤を投与し，その効果を検討した。症例1： 71歳， 排尿困難，左大腿部痛を主訴として1978年6月15日当科受診。前立腺は超鶏卵大，石様硬，表面不整，骨盤へ浸潤。左ソケイ部にくるみ大の硬いリンパ腺を触知。骨シンチで多数の転移を認めた。 前立腺の針生検組織像は分化型腺癌であった。pepleomycin 200 mg (1回10mg，静注， 週3回)の投与により前立腺癌，左ソケイ部リンパ腺の著明な縮小がみられ，血清酸ホスファターゼ値が治療前6.5K.A.U.から9.5K.A.U まで低下した。治療終了後の生検組織像は癌細胞の変性，壊死組織の線維化が目立った。　　症例2: 74歳，排尿困難で1978年8月19日当科受診。前立腺は鶏卵大，硬，周囲に浸潤。骨シンチで転移巣が多数あり，前立腺生検組織像は未分化型腺癌であった。 pepleomycin投与で自覚症状は症例1ほどの改善はみられず，前立腺癌そのものもあまり縮小しなかったが，残尿は80mlから10mlへ減少した。治療後の前立腺生検所見でも癌細胞の空胞化が著明に認められた。なお副作用としては症例1では著明な皮膚変化がみられたが，症例2でぎ軽度の口内炎を認めるにとどまった。NK 631 投与前後で血中FSH，LH，testosteroneを測定したところ，両症例ともに投与終了後FSH，LH，t estosterone値は投与前値の約1/2となっていた (Table 2)。 つまり， NK 631 の抗腫瘍作用はDNA合成抑制によるということになっているが，前立腺癌に対する抗腫聖書効果はNK631 の下重体抑制による睾丸のLeydig cellよりのandrogen分泌抑制も関与している可能性があることが示唆された。本剤の下垂体抑制効果については今後検討されるべき課題であると考える。Since the new bleomycin derivative-pepleomycin was reported to be effective for experimentally induced adenocarcinoma of stomach in rats, it was administered in two cases of prostatic cancer. Satisfactory response was obtained in well differentiated carcinoma, meanwhile only histological effect was observed in undifferentiated one. It seems that the effect of pepleomycin on prostatic cancer was brought about by the suppression of DNA synthesis of tumor and also of pituitary function resulting in decreased androgen secretion from Leydig cells

Correction of an asymmetric maxillary dental arch by alveolar bone distraction osteogenesis

This case report describes a new surgical orthodontic approach involving alveolar bone distraction osteogenesis for correction of an asymmetric maxillary dental arch. The treatment was combined with conventional orthognathic surgery to improve the mandibular lateral deviation. This new treatment strategy produced an ideal dental arch and a symmetric facial appearance efficiently and effectively

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Crystal structure of the flexible tandem repeat domain of bacterial cellulose synthesis subunit C

Bacterial cellulose (BC) is synthesized and exported through the cell membrane via a large protein complex (terminal complex) that consists of three or four subunits. BcsC is a little-studied subunit considered to export BC to the extracellular matrix. It is predicted to have two domains: a tetratrico peptide repeat (TPR) domain and a beta-barrelled outer membrane domain. Here we report the crystal structure of the N-terminal part of BcsC-TPR domain (Asp24-Arg272) derived from Enterobacter CJF-002. Unlike most TPR-containing proteins which have continuous TPR motifs, this structure has an extra a-helix between two clusters of TPR motifs. Five independent molecules in the crystal had three different conformations that varied at the hinge of the inserted a-helix. Such structural feature indicates that the inserted a-helix confers flexibility to the chain and changes the direction of the TPR super-helix, which was also suggested by structural analysis of BcsC-TPR (Asp24-Leu664) in solution by size exclusion chromatography-small-angle X-ray scattering. The flexibility at the a-helical hinge may play important role for exporting glucan chains

Involvement of casein kinase 1 epsilon/delta (Csnk1e/d) in the pathogenesis of familial Parkinson's disease caused by CHCHD2

Abstract Parkinson's disease (PD) is a common neurodegenerative disorder that results from the loss of dopaminergic neurons. Mutations in coiled‐coil‐helix‐coiled‐coil‐helix domain containing 2 (CHCHD2) gene cause a familial form of PD with α‐Synuclein aggregation, and we here identified the pathogenesis of the T61I mutation, the most common disease‐causing mutation of CHCHD2. In Neuro2a cells, CHCHD2 is in mitochondria, whereas the T61I mutant (CHCHD2T61I) is mislocalized in the cytosol. CHCHD2T61l then recruits casein kinase 1 epsilon/delta (Csnk1e/d), which phosphorylates neurofilament and α‐Synuclein, forming cytosolic aggresomes. In vivo, both Chchd2T61I knock‐in and transgenic mice display neurodegenerative phenotypes and aggresomes containing Chchd2T61I, Csnk1e/d, phospho‐α‐Synuclein, and phospho‐neurofilament in their dopaminergic neurons. Similar aggresomes were observed in a postmortem PD patient brain and dopaminergic neurons generated from patient‐derived iPS cells. Importantly, a Csnk1e/d inhibitor substantially suppressed the phosphorylation of neurofilament and α‐Synuclein. The Csnk1e/d inhibitor also suppressed the cellular damage in CHCHD2T61I‐expressing Neuro2a cells and dopaminergic neurons generated from patient‐derived iPS cells and improved the neurodegenerative phenotypes of Chchd2T61I mutant mice. These results indicate that Csnk1e/d is involved in the pathogenesis of PD caused by the CHCHD2T61I mutation