Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety

<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) stimulates hepatocyte proliferation, and also acts as an anti-apoptotic factor. Therefore, HGF is a potential therapeutic agent for treatment of fatal liver diseases. We performed a translational medicine protocol with recombinant human HGF (rh-HGF), including a phase I/II study of patients with fulminant hepatitis (FH) or late-onset hepatic failure (LOHF), in order to examine the safety, pharmacokinetics, and clinical efficacy of this molecule.</p> <p>Methods</p> <p>Potential adverse effects identified through preclinical safety tests with rh-HGF include a decrease in blood pressure (BP) and an increase in urinary excretion of albumin. Therefore, we further investigated the effect of rh-HGF on circulatory status and renal toxicity in preclinical animal studies. In a clinical trial, 20 patients with FH or LOHF were evaluated for participation in this clinical trial, and four patients were enrolled. Subjects received rh-HGF (0.6 mg/m²/day) intravenously for 12 to 14 days.</p> <p>Results</p> <p>We established an infusion method to avoid rapid BP reduction in miniature swine, and confirmed reversibility of renal toxicity in rats. Although administration of rh-HGF moderately decreased BP in the participating subjects, this BP reduction did not require cessation of rh-HGF or any vasopressor therapy; BP returned to resting levels after the completion of rh-HGF infusion. Repeated doses of rh-HGF did not induce renal toxicity, and severe adverse events were not observed. Two patients survived, however, there was no evidence that rh-HGF was effective for the treatment of FH or LOHF.</p> <p>Conclusions</p> <p>Intravenous rh-HGF at a dose of 0.6 mg/m²was well tolerated in patients with FH or LOHF; therefore, it is desirable to conduct further investigations to determine the efficacy of rh-HGF at an increased dose.</p

シンリガク キョウイク ニカンスル ガクセイ ニーズ ノ ケントウ : ガクブ ガクセイ･ダイガクインセイ オ タイショウ ト シタ チョウサ カラ

本研究では，大学生・大学院生の心理学教育に対するニーズを明らかにするため2つの調査を実施した。研究1では，学部学生を対象に進学動機や心理学教育に対する認識，ニーズ等に関する質問紙調査を実施した。研究2では，大学院生を対象に学部教育と大学院教育の連携に関するインタビュー調査を実施した。分析の結果，興味関心がある授業と就職のための授業を区別する対処を学生が行なっていること，早い段階で将来の見通しを学生が持てるような対応をしていくことが必要なこと（研究1），および学部学生と大学院生とでは求める学びに違いがあること，大学院では学びの捉え直しが生じること，資格取得のための受身的動機が強いこと（研究2）が明らかとなった。以上のことから，インターンシップやボランティア体験を通じ，授業で学んだ心理学を積極的に活用する機会を学びの中に設けることによる，心理学の有用性に関する理解の前倒しが心理学教育には有効であると考えられる。In this study, two surveys were conducted to clarify the needs of undergraduate and graduate students for psychology education. In Study1, a questionnaire survey was conducted on undergraduate students’ motivations, awareness of psychology education, needs, etc. In Study2, an interview survey on collaboration between undergraduate and postgraduate education was conducted for graduate students. It was found the students took action to distinguish between classes of interest and classes for employment, and it is useful to cope with the prospects of the future at an early stage （Study1）, and that there was discrepancy between learning sought by undergraduate students and that by graduate students, they rethink learning in graduate schools, and that there is strong passive motivations for acquiring qualifications （Study2）. Therefore, it is considered effective for psychology education to accelerate understanding by providing opportunities to actively use psychology learned in class through internships and volunteer experiences

Immaturin-Nuclease as a Model System for a Gene-Programmed Sexual Development and Rejuvenescence in <i>Paramecium</i> Life History

Fertilization-initiated development and adult-onset aging are standard features in the life history of eukaryotes. In Paramecium, the number of cell divisions after the birth of a new generation is an essential parameter of sexual phase transition and aging. However, the gene driving this process and its evolutionary origin have not yet been elucidated. Here we report several critical outcomes obtained by molecular genetics, immunofluorescence microscopy, transformation by microinjection, and enzymological analysis. The cloned immaturin gene induces sexual rejuvenation in both mature and senescent cells by microinjection. The immaturin gene originated from proteobacteria’s glutathione-S-transferase (GST) gene. However, immaturin has been shown to lose GST activity and instead acquire nuclease activity. In vitro substrates for immaturin-nuclease are single- and double-stranded DNA, linear and circular DNA, and single-stranded viral genome RNA such as coronavirus. Anti-immaturin antibodies have shown that the subcellular localizations of immaturin are the macronucleus, cytoplasm, cell surface area, and cilia. The phase transition of sexuality is related to a decrease in the intracellular abundance of immaturin. We propose that sexual maturation and rejuvenation is a process programmed by the immaturin gene, and the sexual function of each age is defined by both the abundance and the intracellular localization mode of the immaturin-nuclease

Sustained heterozygosity across a self-incompatibility locus in an inbred ascidian.

Because self-incompatibility loci are maintained heterozygous and recombination within self-incompatibility loci would be disadvantageous, self-incompatibility loci are thought to contribute to structural and functional differentiation of chromosomes. Although the hermaphrodite chordate, Ciona intestinalis, has two self-incompatibility genes, this incompatibility system is incomplete and self-fertilization occurs under laboratory conditions. Here, we established an inbred strain of C. intestinalis by repeated self-fertilization. Decoding genome sequences of sibling animals of this strain identified a 2.4-Mbheterozygous region on chromosome 7. A self-incompatibility gene, Themis-B, was encoded within this region. This observation implied that this self-incompatibility locus and the linkage disequilibrium of its flanking region contribute to the formation of the 2.4-Mb heterozygous region, probably through recombination suppression. We showed that different individuals in natural populations had different numbers and different combinations of Themis-B variants, and that the rate of self-fertilization varied among these animals. Our result explains why self-fertilization occurs under laboratory conditions. It also supports the concept that the Themis-B locus is preferentially retained heterozygous in the inbred line and contributes to the formation of the 2.4-Mb heterozygous region. High structural variations might suppress recombination, and this long heterozygous region might represent a preliminary stage of structural differentiation of chromosomes

Hepatic Resection by combined Use of Microwave Tissue Coagulator and C.U.S.A. System under Intraoperative Ultrasonographic Guidance

To control the bleeding during hepatic resection, especially in the patients with liver cirrhosis, is an extremely important factor to prevent the development of postoperative hepatic failure. For this purpose, we have been using a. hepatic resection method combining the use of a microwave tissue coagulator and intraoperative ultrasonic examination and the cavitron ultrasonic surgical aspiration system in recent years. In this procedure, first, the liver is dissected to decide which part to resect using the intraoperative ultrasonography. Second, the hepatic parenchym is coagulated by Microwave. Third, the coagulated necrotic tissues are emulsified and aspirated by C.U.S.A. Fourth, the liver is resected by carefully ligating and dividing the remaining vessels. This procedure made it possible to control completely the bleeding from liver parenchym during hepatic resection. We also emphasized that C.U.S.A. were well applicable for hepatic resection even in cirrhotic liver when it followed microwave tissue coagulation

Femtosecond time-resolved X-ray absorption spectroscopy of liquid using a hard X-ray free electron laser in a dual-beam dispersive detection method

世界で初めて、X線自由電子レーザーを用いたフェムト秒領域でのX線直接吸収分光測定に成功 -極短時間に起こる化学反応の追跡手法をSACLAで実証-. 京都大学プレスリリース. 2014-01-13.We present femtosecond time-resolved X-ray absorption spectroscopy of aqueous solution using a hard x-ray free electron laser (SACLA) and a synchronized Ti:sapphire laser. The instrumental response time is 200 fs, and the repetition rate of measurement is 10 Hz. A cylindrical liquid beam 100 μm in diameter of aqueous ammonium iron(III) oxalate solution is photoexcited at 400 nm, and the transient X-ray absorption spectra are measured in the K-edge region of iron, 7.10 − 7.26 keV, using a dual X-ray beam dispersive detection method. Each of the dual beams has the pulse energy of 1.4 μJ, and pump-induced absorbance change on the order of 10−3 is successfully detected. The photoexcited iron complex exhibits a red shifted iron K-edge with the appearance time constant of 260 fs. The X-ray absorption difference spectra, with and without the pump pulses, are independent of time delay after 1.5 ps up to 100 ps, indicating that the photoexcited species is long-lived