Early evolution of spherical ejecta expanding into the circumstellar matter at ultra-relativistic speeds

We present a new self-similar solution describing early evolution of an ultra-relativistic flow resulting from a collision of homologously expanding spherical ejecta with the circumstellar matter, in which a shock wave propagates in the circumstellar matter while a weak discontinuity propagates in the ejecta at the sound speedComment: 5 pages, 2 figures, accepted for publication in PAS

Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential

Sepsis-induced multiple organ failure (MOF) is the most frequent lethal disease in intensive care units. Thus, it is important to elucidate the self-defensive mechanisms of sepsis-induced MOF. Hepatocyte growth factor (HGF) is now recognized as an organotrophic factor, which is essential for organogenesis during embryonic growth and regeneration in adulthood. HGF production is enhanced in response to infectious challenges, but the increase in endogenous HGF levels is transient and insufficient, with a time lag between tissue injuries and HGF upregulation, during progression of septic MOF. Thus, administration of active-formed HGF might be a new candidate for therapeutic development of MOF. HGF has an ability to target endotoxin-challenged macrophages and inhibits the upregulation of inflammatory cytokines through nuclear factor-κB-inactivated mechanisms. HGF also targets the endothelium and epithelium of various organs to suppress local inflammation, coagulation, and apoptotic death. This paper summarizes the novel mechanisms of HGF for attenuating sepsis-related pathological conditions with a focus on sepsis-induced MOF

Self-similar solutions for the interaction of relativistic ejecta with an ambient medium

We find self-similar solutions to describe the interaction of spherically symmetric ejecta expanding at relativistic speeds with an ambient medium having a power law density distribution. Using this solution, the time evolution of the Lorentz factor of the outer shock is derived as a function of the explosion energy, the mass of the ejecta, and parameters for the ambient medium. These solutions are an ultra-relativistic version of the solutions for the circumstellar interaction of supernova ejecta obtained by Chevalier and extensions of the relativistic blast wave solutions of Blandford & Mckee.Comment: 12 pages, 1 figure, accepted for publication in Ap

Implication of Tryptophan 2,3-Dioxygenase and its Novel Variants in the Hippocampus and Cerebellum During the Developing and Adult Brain

Tryptophan 2,3-dioxygenase (TDO) is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism. Using Tdo−/− mice, we have recently shown that TDO plays a pivotal role in systemic tryptophan metabolism and brain serotonin synthesis as well as emotional status and adult neurogenesis. However, the expression of TDO in the brain has not yet been well characterized, in contrast to its predominant expression in the liver. To further examine the possible role of local TDO in the brain, we quantified the levels of tdo mRNA in various nervous tissues, using Northern blot and quantitative real-time RT-PCR. Higher levels of tdo mRNA expression were detected in the cerebellum and hippocampus. We also identified two novel variants of the tdo gene, termed tdo variant1 and variant2, in the brain. Similar to the known TDO form (TDO full-form), tetramer formation and enzymatic activity were obtained when these variant forms were expressed in vitro. While quantitative real-time RT-PCR revealed that the tissue distribution of these variants was similar to that of tdo full-form, the expression patterns of these variants during early postnatal development in the hippocampus and cerebellum differed. Our findings indicate that in addition to hepatic TDO, TDO and its variants in the brain might function in the developing and adult nervous system. Given the previously reported associations of tdo gene polymorphisms in the patients with autism and Tourette syndrome, the expression of TDO in the brain suggests the possible influence of TDO on psychiatric status. Potential functions of TDOs in the cerebellum, hippocampus and cerebral cortex under physiological and pathological conditions are discussed

Hepatocyte growth factor and Met in tumor biology and therapeutic approach with NK4

金沢大学がん研究所分子標的がん医療研究開発センターHepatocyte growth factor (HGF) and Met/HGF receptor tyrosine kinase play a role in the progression to invasive and metastatic cancers. A variety of cancer cells secrete molecules that enhance HGF expression in stromal fibroblasts, while fibroblast-derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. In addition to the ligand-dependent activation, Met receptor activation is negatively regulated by cell-cell contact and Ser985 phosphorylation in the juxtamembrane of Met. The loss of intercellular junctions may facilitate an escape from the cell-cell contact-dependent suppression of Met-signaling. Significance of juxtamembrane mutations found in human cancers is assumed to be a loss-of-function in the negative regulation of Met. In attempts to block the malignant behavior of cancers, NK4 was isolated as a competitive antagonist against HGF-Met signaling. Independently on its HGF-antagonist action, NK4 inhibited angiogenesis induced by vascular endothelial cell growth factor and basic fibroblast growth factor, as well as HGF. In experimental models of distinct types of cancers, NK4 inhibited Met activation and this was associated with inhibition of tumor invasion and metastasis. NK4 inhibited tumor angiogenesis, thereby suppressing angiogenesis-dependent tumor growth. Cancer treatment with NK4 suppresses malignant tumors to be "static" in both tumor growth and spreading. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA

Hepatocyte growth factor twenty years on: Much more than a growth factor

金沢大学がん研究所Liver regeneration depends on the proliferation of mature hepatocytes. In the 1980s, the method for the cultivation of mature hepatocytes provided an opportunity for the discovery of hepatocyte growth factor (HGF) as a protein that is structurally and functionally different from other growth factors. In 1991, the scatter factor, tumor cytotoxic factor, and 3-D epithelial morphogen were identified as HGF, and Met tyrosine kinase was identified as the receptor for HGF. Thus, the connection of apparently unrelated research projects rapidly enriched the research on HGF in different fields. The HGF-Met pathway plays important roles in the embryonic development of the liver and the placenta, in the migration of myogenic precursor cells, and in epithelial morphogenesis. The use of tissue-specific knockout mice demonstrated that in mature tissues the HGF-Met pathway plays a critical role in tissue protection and regeneration, and in providing less susceptibility to chronic inflammation and fibrosis. In various injury and disease models, HGF promotes cell survival, regeneration of tissues, and suppresses and improves chronic inflammation and fibrosis. Drug development using HGF has been challenging, but extensive preclinical studies to address its therapeutic effects have provided significant results sufficient for the development of HGF as a biological drug in the regeneration-based therapy of diseases. Clinical trials using recombinant human HGF protein, or HGF genes, are in progress for the treatment of diseases. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

Mobile locally operated detachable end-effector manipulator for endoscopic surgery

Purpose\n Local surgery is safer than remote surgery because emergencies can be more easily addressed. Although many locally operated surgical robots and devices have been developed, none can safely grasp organs and provide traction. A new manipulator with a detachable commercial forceps was developed that can act as a third arm for a surgeon situated in a sterile area near the patient. This mechanism can be disassembled into compact parts that enable mobile use.Methods\n A mobile locally operated detachable end-effector manipulator (LODEM) was developed and tested. This device uses crank-slider and cable-rod mechanisms to achieve 5 degrees of freedom and an acting force of more than 5 N. The total mass is less than 15 kg. The positional accuracy and speed of the prototype device were evaluated while performing simulated in vivo surgery.Results\n The accuracy of the mobile LODEM was 0.4 mm, sufficient for handling organs. The manipulator could be assembled and disassembled in 8 min, making it highly mobile. The manipulator could successfully handle the target organs with the required level of dexterity during an in vivo laparoscopic surgical procedure.Conclusions\n A mobile LODEM was designed that allows minimally invasive robotically assisted endoscopic surgery by a surgeon working near the patient. This device is highly promising for robotic surgery applications.ArticleINTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY. 10(2):161-169 (2015)journal articl