Iwate University, Osaka City University, Iwate Medical University and Lotte Co. | Date: 2017-08-02
Provided is a cyclic peptide derivative which is derived from Paecilomyces tenuipes having an astrocyte proliferative activity, or a salt thereof.
Iwate Medical University | Date: 2017-10-04
To provide methods of creating trait prediction models for predicting phenotypes of traits from single nucleotide polymorphism data and methods of predicting traits with which traits can be predicted with a high accuracy. This is a method of creating a trait prediction model for predicting a phenotype of a multifactorial trait using data of a plurality of single nucleotide polymorphisms linked to a trait for each of a plurality of individuals of an organism: representing each of the plurality of single nucleotide polymorphisms as a matrix; classifying the plurality of single nucleotide polymorphisms into a plurality of categories based on their genetic architectures; calculating, for each of the categories, a genomic similarity matrix using the represented matrix and the number of the single nucleotide polymorphisms belonging to the category; and applying the genomic similarity matrix and a parameter of the genetic architecture to a linear mixed model.
Sanbe A.,Iwate Medical University
Biological and Pharmaceutical Bulletin | Year: 2013
Cardiomyopathies are defined as cardiac diseases of the myocardium with associated cardiac dysfunction. They are cardiac diseases in which heart muscle disease and/or measurable deterioration of cardiac muscle function occurs due to various causes, such as genetic and sporadic mutations of muscle proteins, as well as external factors such as hypertension, ischemia, and inflammation. In 1995, the WHO/International Society and Federation of Cardiology (ISFC) classified primary cardiomyopathy caused by intrinsic factors into five groups according to the dominant pathophysiology: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restricted cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and unclassified cardiomyopathy. Among these cardiomyopathies, DCM is the most prevalent and the most common reason for cardiac transplantation in adults and children. Many recent findings indicate that genetic and sporadic mutations of a number of muscle proteins, such as myofibrillar, structural, and Ca2+ regulating proteins, can cause DCM. In such cases, certain mutations often induce DCM with cardiac arrhythmia that is recognized as a potential trigger of sudden cardiac death. Thus, effective prognostic determination and appropriate cardiac care depend on accurate molecular and genetic diagnoses. © 2013 The Pharmaceutical Society of Japan.
Sanbe A.,Iwate Medical University
Biological and Pharmaceutical Bulletin | Year: 2011
α-B-Crystallin (CryAB, gene map locus: 11q22.3-q23.1) is a member of the small heat shock protein (HSP) family, a group of proteins that prevent protein aggregation upon exposure of a cell to heat and/or restore the biological activity of cell substrates. The missense mutation and the deletion mutation of CryAB can cause various forms of muscular disorder, including restrictive, hypertrophic, and dilated cardiomyopathies, heart failure, and skeletal muscle weakness. Collectively, these diseases constitute a rare autosomal-dominant inherited disorder called α-crystallinopathy (crystallinopathy), also known as desmin-related cardiomyopathy. The disease is a misfolded protein-related disease characterized by the formation of insoluble protein aggregates consisting of the CryAB protein in the patient's cardiomyocytes and skeletal myocytes. The details of crystallinopathy are unclear at the present time; what has been discovered concerning the disease mechanisms underlying crystallinopathy has been through experiments with genetically modified mice such as the CryAB knockout mouse and various mutant CryAB transgenic (TG) mice. Crystallinopathy can be recapitulated in TG mice by expressing the mutant CryAB Arg120Gly (R120G) protein, a causal mutation of crystallinopathy, specifically in the cardiomyocytes. CryAB R120G causes perinuclear formation of aggresomes containing preamyloid oligomer intermediates, which are wellknown as a primary toxic species in neurodegenerative disease. This suggests that crystallinopathy caused by the CryAB mutation could be considered one of the aggresomal and amyloid-related diseases. Moreover, recent findings have indicated that enhancement of HSP induction and inhibition of apoptotic cell death by mitochondrial protection may be a new therapeutic strategy for patients with crystallinopathy. © 2011 Pharmaceutical Society of Japan.
Fujii I.,Iwate Medical University
Journal of Antibiotics | Year: 2010
Fungal polyketides have huge structural diversity from simple aromatics to highly modified complex reduced-type compounds. Despite such diversty, single modular iterative type I polyketide synthases (iPKSs) are responsible for their carbon skeleton construction. Using heterologous expression systems, we have studied on ATX, a 6-methylsalicylic acid synthase from Aspergillus terreus as a model iPKS. In addition, iPKS functions involved in fungal spore pigment biosynthesis were analyzed together with polyketide-shortening enzymes that convert products of PKSs to shorter ketides by hydrolytic C-C bond cleavage. In our studies on reducing-type iPKSs, we cloned and expressed PKS genes, pksN, pksF, pksK and sol1 from Alternaria solani. The sol gene cluster was found to be involved in solanapyrone biosynthesis and sol5 was identified to encode solanapyrone synthase, a Diels-Alder enzyme. Our fungal PKS studies were further extended to identify the function of PKS-nonribosomal peptide synthase involved in cyclopiazonic acid biosynthesis. © 2010 Japan Antibiotics Research Association All rights reserved.
Hicks T.P.,Lakehead University |
Onodera S.,Iwate Medical University
Progress in Neurobiology | Year: 2012
The human red nucleus consists of the well-developed parvicellular red nucleus (pNr) and the rudimentary magnocellular red nucleus (mNr). It is believed that the human pNr is separated from the nucleus accessorius medialis of Bechterew (NB), which, generally speaking, is located in the ventral central gray. It was initially suggested that the " rolled sheet" model of the human pNr that we proposed included the view that the human NB does not occupy the ventral central gray but is placed in the dorsomedial part of the red nucleus. It is perhaps more appropriate to state that the NB, the origin of the medial tegmental tract (MTT), over time became displaced from the ventral central gray and was in part shifted to the adjacent reticular formation. The majority of the MTT tract however remained in its established location. Evolutionarily speaking, this separation of the NB and the nucleus of Darkschewitsch (ND), and the translocation of the position of the NB just referred to, might have begun within the lineage of the apes prior to the emergence of man. Furthermore it is generally believed that the human mNr consists of a scattered few groups of giant-to-large neurons situated among the fiber bundles of the superior cerebellar peduncle at the level of the oculomotor nerve fibers. It has long been considered impossible to clearly draw an outline of the human mNr such that it could be seen as a self-contained structural entity. However, we now demonstrate just such an outline of the rudimentary human adult mNr through employment of the concepts of the so-called " Mannen's closed nucleus" and " Ogawa's human mNr": descriptions that exclude the associated area that contains neurons which possess melanin pigment. Interestingly, recent studies have shown that the human fetus and newborns have a well-developed semilunar mNr, and this observation raises the possibility that the associated transient but well-developed rubrospinal tract seen in the perinatal state might have had an important role for the development of upright bipedalism in hominids. The well-developed human prefrontal-NB-olivo-lateral cerebellar circuit might possibly have resulted in the emergence of language. © 2012 Elsevier Ltd.
Uwano I.,Iwate Medical University
Stroke | Year: 2017
BACKGROUND AND PURPOSE—: The oxygen extraction fraction (OEF) is an effective metric to evaluate metabolic reserve in chronic ischemia. However, OEF is considered to be accurately measured only when using positron emission tomography (PET). Thus, we investigated whether OEF maps generated by magnetic resonance quantitative susceptibility mapping (QSM) at 7 Tesla enabled detection of OEF changes when compared with those obtained with PET. METHODS—: Forty-one patients with chronic stenosis/occlusion of the unilateral internal carotid artery or middle cerebral artery were examined using 7 Tesla-MRI and PET scanners. QSM images were obtained from 3-dimensional T2*-weighted images, using a multiple dipole-inversion algorithm. OEF maps were generated based on susceptibility differences between venous structures and brain tissues on QSM images. OEF ratios of the ipsilateral middle cerebral artery territory against the contralateral side were calculated on the QSM-OEF and PET-OEF images, using an anatomic template. RESULTS—: The OEF ratio in the middle cerebral artery territory showed significant correlations between QSM-OEF and PET-OEF maps (r=0.69; P<0.001), especially in patients with a substantial increase in the PET-OEF ratio of 1.09 (r=0.79; P=0.004), although showing significant systematic biases for the agreements. An increased QSM-OEF ratio of >1.09, as determined by receiver operating characteristic analysis, showed a sensitivity and specificity of 0.82 and 0.86, respectively, for the substantial increase in the PET-OEF ratio. Absolute QSM-OEF values were significantly correlated with PET-OEF values in the patients with increased PET-OEF. CONCLUSIONS—: OEF ratios on QSM-OEF images at 7 Tesla showed a good correlation with those on PET-OEF images in patients with unilateral steno-occlusive internal carotid artery/middle cerebral artery lesions, suggesting that noninvasive OEF measurement by MRI can be a substitute for PET. © 2017 American Heart Association, Inc.
Beppu T.,Iwate Medical University
American Journal of Neuroradiology | Year: 2014
The aim of this article is to review how MR imaging and associated imaging modalities provide clinicopathologic information on brain damage after carbon monoxide poisoning. Initially, many authors documented typical findings of conventional MR imaging in the gray matter structures such as the globus pallidus and in various regions of cerebral white matter. The focus of investigation has since shifted to observation of cerebral white matter areas that are more frequently detected on MR imaging and are more responsible for chronic symptoms than the gray matter. DWI has dramatically contributed to the ability to quantitatively assess cerebral white matter damage. Subsequently, DTI has enabled more sensitive evaluation than DWI and can demonstrate progressive pathologic changes in the early stage, allowing prediction of chronic conditions. In addition, MR spectroscopy reveals changes in metabolite levels, offering quantitative clinicopathologic information on brain damage after carbon monoxide poisoning.
Oku Y.,Iwate Medical University
PLoS ONE | Year: 2014
Accurate chromosome segregation is vital for cell viability. Many cancer cells show chromosome instability (CIN) due to aberrant expression of the genes involved in chromosome segregation. The induction of massive chromosome segregation errors in such cancer cells by small molecule inhibitors is an emerging strategy to kill these cells selectively. Here we screened and characterized small molecule inhibitors which cause mitotic chromosome segregation errors to target cancer cell growth. We screened about 300 chemicals with known targets, and found that Rho-associated coiled-coil kinase (ROCK) inhibitors bypassed the spindle assembly checkpoint (SAC), which delays anaphase onset until proper kinetochoremicrotubule interactions are established. We investigated how ROCK inhibitors affect chromosome segregation, and found that they induced microtubule-dependent centrosome fragmentation. Knockdown of ROCK1 and ROCK2 revealed their additive roles in centrosome integrity. Pharmacological inhibition of LIMK also induced centrosome fragmentation similar to that by ROCK inhibitors. Inhibition of ROCK or LIMK hyper-stabilized mitotic spindles and impaired Aurora-A activation. These results suggested that ROCK and LIMK are directly or indirectly involved in microtubule dynamics and activation of Aurora-A. Furthermore, inhibition of ROCK or LIMK suppressed T cell leukemia growth in vitro, but not peripheral blood mononuclear cells. They induced centrosome fragmentation and apoptosis in T cell leukemia cells. These results suggested that ROCK and LIMK can be a potential target for anti-cancer drugs. © 2014 Oku et al.
Toshiba Corporation and Iwate Medical University | Date: 2015-05-28
According to an embodiment, a medical image processing apparatus includes an extraction unit, a calculation unit, and a selection unit. The extraction unit extracts an image region having an image element value larger than a predetermined value from a first image of at least one time phase and second images of a plurality of time phases. The calculation unit calculates a feature quantity that fluctuates in accordance with motion of the image region for the first image of at least the one time phase and the second images of the time phases. The selection unit selects the first image and the second image having similar image features of the image region based on the feature quantity from among the first image of at least the one time phase and the second images of the time phases.