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Dive into the research topics where Hiroshi Tsujikawa is active.

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Featured researches published by Hiroshi Tsujikawa.


Circulation | 2004

Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression

Kyosuke Takeshita; Toshihiko Fujimori; Yoko Kurotaki; Haruo Honjo; Hiroshi Tsujikawa; Kenji Yasui; Jong-Kook Lee; Kaichiro Kamiya; Kiyoyuki Kitaichi; Koji Yamamoto; Masafumi Ito; Takahisa Kondo; Shigeo Iino; Yasuya Inden; Makoto Hirai; Toyoaki Murohara; Itsuo Kodama; Yo-ichi Nabeshima

Background—Homozygous mutant mice with a defect of klotho gene expression (kl/kl) show multiple age-related disorders and premature death from unknown causes. Methods and Results—The kl/kl mice subjected to 20-hour restraint stress showed a high rate (20/30) of sudden death, which was associated with sinoatrial node dysfunction (conduction block or arrest). Heart rate and plasma norepinephrine of kl/kl mice, unlike those of wild-type (WT) mice, failed to increase during the stress. Intrinsic heart rate after pharmacological blockade of autonomic nerves in kl/kl mice was significantly lower than that in WT mice (380±33 versus 470±44 bpm; n=7). The sinus node recovery time after an overdrive pacing (600 bpm, 30 seconds) in kl/kl mice was significantly longer than in WT mice (392±37 versus 233±24 ms; n=6). In isolated sinoatrial node preparations, the positive chronotropic effect of isoproterenol was significantly less, whereas the negative chronotropic effect of acetylcholine was significantly greater in kl/kl than in WT mice. There was no degenerative structural change in the sinoatrial node of kl/kl mice. The precise localization of klotho was analyzed in newly prepared klotho-null mice with a reporter gene system (kl−geo). Homozygous kl− geo mice showed characteristic age-associated phenotypes that were almost identical to those of kl/kl mice. In the kl− geo mice, klotho expression was recognized exclusively in the sinoatrial node region in the heart in addition to parathyroid, kidney, and choroid plexus. Conclusions—In the heart, klotho is expressed solely at the sinoatrial node. klotho gene expression is essential for the sinoatrial node to function as a dependable pacemaker under conditions of stress.


Proceedings of the National Academy of Sciences of the United States of America | 2007

A new Late Miocene great ape from Kenya and its implications for the origins of African great apes and humans

Yutaka Kunimatsu; Masato Nakatsukasa; Yoshihiro Sawada; Tetsuya Sakai; Masayuki Hyodo; Hironobu Hyodo; Tetsumaru Itaya; Hideo Nakaya; Haruo Saegusa; Arnaud Mazurier; Mototaka Saneyoshi; Hiroshi Tsujikawa; Ayumi Yamamoto; Emma Mbua

Extant African great apes and humans are thought to have diverged from each other in the Late Miocene. However, few hominoid fossils are known from Africa during this period. Here we describe a new genus of great ape (Nakalipithecus nakayamai gen. et sp. nov.) recently discovered from the early Late Miocene of Nakali, Kenya. The new genus resembles Ouranopithecus macedoniensis (9.6–8.7 Ma, Greece) in size and some features but retains less specialized characters, such as less inflated cusps and better-developed cingula on cheek teeth, and it was recovered from a slightly older age (9.9–9.8 Ma). Although the affinity of Ouranopithecus to the extant African apes and humans has often been inferred, the former is known only from southeastern Europe. The discovery of N. nakayamai in East Africa, therefore, provides new evidence on the origins of African great apes and humans. N. nakayamai could be close to the last common ancestor of the extant African apes and humans. In addition, the associated primate fauna from Nakali shows that hominoids and other non-cercopithecoid catarrhines retained higher diversity into the early Late Miocene in East Africa than previously recognized.


Primates | 2004

Preliminary analysis of Nacholapithecus scapula and clavicle from Nachola, Kenya

Brigitte Senut; Masato Nakatsukasa; Yutaka Kunimatsu; Yoshihiko Nakano; Tomo Takano; Hiroshi Tsujikawa; Daisuke Shimizu; Miyuki Kagaya; Hidemi Ishida

The Miocene ape Nacholapithecus is known from rather complete skeletons; some of them preserve the shoulder joint, identified by three scapulae and one clavicle. Comparisons made with other Miocene and living apes (Proconsul, Equatorius, Ugandapithecus) suggest that the mobility of the scapulohumeral joint was important, and scapular features such as the morphology and position of the spine and the morphology of the acromion and axillary border resemble those of climbing arboreal primates except for chimpanzees, gorillas, or orang-utans. From the size of the scapula (male Nasalis size), it is clear that the animal is smaller than an adult chimpanzee, but the clavicle is almost as relatively long as those of chimpanzees. Some features closer to colobine morphology reinforce the hypothesis that Nacholapithecus was probably a good climber and was definitely adapted for an arboreal life.


Biochimica et Biophysica Acta | 2009

Morphine induces DNA damage and P53 activation in CD3+ T cells.

Hiroshi Tsujikawa; Takehiro Shoda; Toshiyuki Mizota; Kazuhiko Fukuda

BACKGROUND Morphine has been shown to affect the function of immune system, but the precise mechanism remains to be elucidated. The present study was aimed to clarify the mechanism for the morphine-induced immune suppression by analyzing the direct effect of morphine on human CD3+ T cells. METHODS To identify genes up-regulated by action of morphine on the opioid receptor expressed in CD3+ T cells, PCR-select cDNA subtraction was performed by the use of total RNA from human CD3+ T cells treated with morphine in the presence and absence of naloxone. RESULTS We show that p53 and damage-specific DNA binding protein 2 (ddb2) genes are up-regulated by morphine in a naloxone-sensitive manner. Furthermore, the results indicate that DNA damage, quantified by apurinic-apyrimidinic site counting assay and phosphorylation of Ser-15 in P53 protein, is induced in CD3+ T cells by morphine in a naloxone-sensitive manner. GENERAL SIGNIFICANCE Because it was shown that only the kappa opioid receptor gene is expressed in CD3+ T cells in the opioid receptor family, the present study suggests that morphine induces DNA damage through the action on the kappa opioid receptor, which leads to immune suppression by activation of P53-mediated signal transduction.


Paleontological Research | 2005

A partial cranium of Diamantohyus nadirus from the Aka Aiteputh Formation (16-15 Ma), Kenya

Martin Pickford; Hiroshi Tsujikawa

ABSTRACT Sanitheres are poorly understood suiforms of small body size. Recent advances in knowledge have been made, especially regarding their postcranial skeleton, but, apart from dentognathic remains, the cranium remains incompletely known. Field work in the Middle Miocene Aka Aiteputh Formation, near Baragoi, Kenya, has resulted in the recovery of a snout and a crushed neurocranium of Diamantohyus nadirus which throw a great deal of light on the systematic affinities of the sanitheres, but do not completely resolve their phylogenetic status.


Journal of Anesthesia | 2013

Dual modulation of the T-cell receptor-activated signal transduction pathway by morphine in human T lymphocytes

Toshiyuki Mizota; Hiroshi Tsujikawa; Takehiro Shoda; Kazuhiko Fukuda

PurposeIn this study, we aimed to investigate the effect of morphine on the activation of extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB), both of which play crucial roles in T-cell activation.MethodsHuman CD3+ T cells and Jurkat T cells were stimulated by anti-CD3 antibody or phorbol 12-myristate 13-acetate plus ionomycin with or without 24-h pretreatment with morphine. Activation of ERK was assessed by immunoblot analysis of phosphorylated ERK. Activation of the NF-κB signaling pathway was examined by analyzing nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation using immunoblotting, and interleukin-2 (IL-2) gene expression using quantitative real-time reverse-transcriptase polymerase chain reaction.ResultsMorphine pretreatment enhanced ERK phosphorylation, but inhibited IκBα phosphorylation and IL-2 gene expression in activated T cells. The effects of morphine on ERK phosphorylation and IL-2 gene expression were not antagonized by naloxone. We detected κ-opioid receptor transcript in T cells, but U50,488, a κ-receptor-selective agonist, did not enhance ERK phosphorylation.ConclusionMorphine enhances ERK signaling, whereas it inhibits NF-κB signaling in activated human T cells. These effects of morphine are unlikely to be mediated by known opioid receptors.


American Journal of Physical Anthropology | 2016

Carpal bones of Nacholapithecus kerioi, a Middle Miocene Hominoid From Northern Kenya.

Naomichi Ogihara; Sergio Almécija; Masato Nakatsukasa; Yoshihiko Nakano; Yasuhiro Kikuchi; Yutaka Kunimatsu; Haruyuki Makishima; Daisuke Shimizu; Tomo Takano; Hiroshi Tsujikawa; Miyuki Kagaya; Hidemi Ishida

OBJECTIVES The carpal bones of the middle Miocene hominoid Nacholapithecus kerioi are described based on new materials. MATERIALS AND METHODS The materials comprise a trapezoid, three capitates, two hamates, a centrale, a lunate, a triquetrum, and a pisiform, collected during the 2001 and 2002 field seasons from Nachola, Kenya. We also describe a pisiform recently assigned to the type specimen of N. kerioi, KNM-BG 35250. RESULTS In the Nacholapithecus wrist, the ulnar styloid process articulates with both the triquetrum and pisiform, and the triquetrum facet on the hamate is relatively proximodistally oriented in dorsal view. The Nacholapithecus capitate possesses a moderate distopalmar hook-like process and separated radial articular facets for the trapezoid and the second metacarpal due to the carpometacarpal ligament attachment that is absent in the Proconsul capitate. DISCUSSION The carpal anatomy of Nacholapithecus is similar to that of the early Miocene hominoid Proconsul. However, Nacholapithecus wrist anatomy appears to exhibit slightly more emphasized stability. Am J Phys Anthropol 160:469-482, 2016.


Archive | 2006

Late Cenozoic Mammalian Biostratigraphy And Faunal Change

Hideo Nakaya; Hiroshi Tsujikawa

The Late Miocene mammalian faunas of sub-Saharan Africa, especially the Namurungule Fauna, indicate a close similarity with the Turolian faunas from sub-Paratethys and North Africa. The Miocene mammalian faunas of sub-Saharan Africa show resemblances with late Vallesian to Turolian ones of North Africa, sub-Paratethys, Southwest and Central Europe faunas.


Emergency Medicine Australasia | 2013

Spinal Epidural Hematoma Following Epidural Anesthesia Managed Safely Without Surgery: A Case Report

Hiroshi Tsujikawa; Masahiro Kakuyama; Kazuhiko Fukuda

Spinal Epidural Hematoma (SEH) is known to occur as a complication of invasive spinal procedures, such as epidural anesthesia, and can cause dramatic neurologic deficits if not diagnosed and treated immediately. The present report describes the case of a gynecologic patient who presented with weakness and numbness of both lower limbs soon after an epidural test bolus was injected. Urgent magnetic resonance imaging of the thoracic spine demonstrated an epidural hematoma at T12/L1 with slight spinal cord compression. The patient demonstrated significant improvement in neurologic deficits within a short time. Therefore, general anesthesia was induced, and the scheduled operation was performed uneventfully. After the operation, the patient had no detectable neurologic abnormality, and repeat imaging showed almost complete resolution of the hematoma. Although urgent decompression is the treatment of choice for SEH, conservative management may be indicated if the patient demonstrates rapidly improving neurologic deficits.


Molecular Endocrinology | 2003

Klotho, a Gene Related to a Syndrome Resembling Human Premature Aging, Functions in a Negative Regulatory Circuit of Vitamin D Endocrine System

Hiroshi Tsujikawa; Yoko Kurotaki; Toshihiko Fujimori; Kazuhiko Fukuda; Yo-ichi Nabeshima

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Hidemi Ishida

University of Shiga Prefecture

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Daisuke Shimizu

Yokohama City University Medical Center

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