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Y Watanabe

Publications and source records attributed to Y Watanabe.

At least 145 records · Page 8Linked to original sources

Endomorphins 1 and 2, endogenous mu-opioid receptor agonists, impair passive avoidance learning in mice.

The effects of intracerebroventricular administration of endomorphin-1 and endomorphin-2, endogenous mu-opioid receptor agonists, on passive avoidance learning associated with long-term memory were investigated in mice. Endomorphin-1 (10 and 17.5 microg) and endomorphin-2 (17.5 microg) produced a significant decrease in step-down latency in a passive avoidance learning task. beta-Funaltrexamine (5 microg) almost completely reversed the endomorphin-1 (17.5 microg)- and endomorphin-2 (17.5 microg)-induced shortening of step-down latency, although neither naltrindole (4 ng) nor nor-binaltorphimine (4 microg) produced any significant effects on the effects of endomorphins 1 and 2. These results suggest that endomorphins 1 and 2 impair long-term memory through the mediation of mu-opioid receptors in the brain.

Analgesics, Opioid↗

Remote verification in radiotherapy using digitally reconstructed radiography (DRR) and portal images: a pilot study.

PURPOSE: To use digitally reconstructed radiography (DRR) and digitally compressed portal images in distant consultation using a telecommunications network, the verification performance of DRR and digitally compressed portal images on the image console was investigated. METHODS AND MATERIALS: A human thoracic phantom was scanned with computed tomography (CT). Radiotherapy was planned at 5 different anatomic locations. A digitally reconstructed radiograph was made; verification films of the phantom were then taken with 6-MV X-rays. The treatment center was intentionally dislocated. Fifty sets of DRR and portal images were seen by 7 doctors on a conventional view-box (view-box method) to judge whether the treatment center was dislocated. These image sets were digitalized by a film scanner, compressed to 1/10 Joint Photographic Experts Group (JPEG) format, and compared on an image console by the same physicians (image-console method). The verification performance of the image console method was compared with that of the view-box method by means of receiver operating characteristic (ROC) analysis. Clinically, 159 portal-image-sets were verified with the image-console method and the appropriateness of the decision was later assessed by the view-box method. RESULTS: The accuracy of the treatment verification was estimated to be 88.8% by the conventional view-box method and 88.3% by the image-console method. There was no statistically significant difference in the verification performances of the conventional method (Az = 0.86+/-0.02) and the image console method (Az = 0.84+/-0.07). Frequent digital image-processing modification was positively related to the accuracy of verification. Clinically, there were 3 (1.8%) major corrections, 31 (19.5%) minor corrections, and 123 cases with no correction. No further correction was called for by the re-evaluation using the view-box method. CONCLUSION: The verification performance of DRR and digitally compressed portal images on the image console was as accurate as the conventional method. Distant consultation using DRR and portal images through telecommunication is usable in clinical practice.

Humans↗

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗

Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxin-induced fever.

Fever is triggered by an elevation of prostaglandin E(2) (PGE(2)) in the brain. However, the mechanism of its elevation remains unanswered. We herein cloned the rat glutathione-dependent microsomal prostaglandin E synthase (mPGES), the terminal enzyme for PGE(2) biosynthesis, and examined its induction in the rat brain after intraperitoneal injection of pyrogen lipopolysaccharide (LPS). In Northern blot analysis, mPGES mRNA was weakly expressed in the brain under the normal conditions but was markedly induced between 2 and 4 hr after the LPS injection. In situ hybridization study revealed that LPS-induced mPGES mRNA signals were mainly associated with brain blood vessels, especially vein or venular-type ones, in the whole brain area. Immunohistochemical study demonstrated that mPGES-like immunoreactivity was expressed in the perinuclear region of brain endothelial cells, which were identified as von Willebrand factor-positive cells. Furthermore, in the perinuclear region of the endothelial cells, mPGES was colocalized with cyclooxygenase-2 (COX-2), which is the enzyme essential for the production of the mPGES substrate PGH(2). Inhibition of cyclooxygenase-2 activity resulted in suppression of both PGE(2) level in the CSF and fever (Cao et al., 1997), suggesting that the two enzymes were functionally linked and that this link is essential for fever. These results demonstrate that brain endothelial cells play an essential role in the PGE(2) production during fever by expressing COX-2 and mPGES.

Animals↗

Hand-assisted laparoscopic total colorectal resection for familial adenomatous polyposis with coexisting rectal cancer.

When familial adenomatous polyposis (FAP) is diagnosed in a patient, prophylactic surgery must be performed whether colorectal cancer is present or not. Operations for FAP have been performed through a large median abdominal incision or an additional perineal incision, depending on the coexistence of rectal cancer. Recently, we reported a technique of laparoscopic rectal amputation without abdominal skin incision for patients with rectal cancer to minimize postoperative cardiac and respiratory complications [6]. In this article, we report a case of laparoscopically assisted proctocolectomy with ileostomy through a minimal abdominal and perineal skin incision performed by a hand-assisted procedure. The purpose of combining the perineal and laparoscopic approaches is to minimize the skin incision, while retaining a rate of cure and safety equivalent to those of conventional rectal amputation, by using the advantages of laparoscopic procedures, and to facilitate postoperative recovery and improve the quality of life for relatively young patients with FAP.

Adenomatous Polyposis Coli↗

Thrombin activates p38 mitogen-activated protein kinase in vascular smooth muscle cells.

Thrombin is a potent mitogen for vascular smooth muscle cells. However, the signaling pathways by which thrombin mediates its mitogenic response are not fully understood. The ERK (extracellular signal-regulated protein kinase) and JNK (c-Jun N-terminal kinase) members of the mitogen-activated protein kinase (MAPK) family are reported to be activated by thrombin. We have investigated the response to thrombin of another member of the MAPK family, p38 MAPK, which has been suggested to be activated by both stress and inflammatory stimuli in vascular smooth muscle cells. We found that thrombin induced time- and dose-dependent activation of p38 MAPK. Maximal stimulation of p38 MAPK was observed after a 10-min incubation with 1 unit ml(-1) thrombin. GF109203X, a protein kinase C inhibitor, and prolonged treatment with phorbol 12-myristate 13-acetate partially inhibited p38 MAPK activation. A tyrosine kinase inhibitor, genistein, also inhibited p38 MAPK activation in a dose-dependent manner. p38 MAPK activation was inhibited by overexpression of betaARK1ct (beta-adrenergic receptor kinase I C-terminal peptide). p38 MAPK activation was also inhibited by expression of dominant-negative Ras, not by dominant-negative Rac. We next examined the effect of a p38 MAPK inhibitor, SB203580, on thrombin-induced proliferation. SB203580 inhibited thrombin-induced DNA synthesis in a dose-dependent manner. These results suggest that thrombin activates p38 MAPK in a manner dependent on Gbetagamma, protein kinase C, a tyrosine kinase, and Ras, that p38 MAPK has a role in thrombin-induced mitogenic response in the cells.

Animals↗

Ultrasound activates the auditory cortex of profoundly deaf subjects.

Using three-dimensional PET, the cortical areas activated by bone-conducted ultrasound were measured from five profoundly deaf subjects and compared with the cortical areas of normal-hearing subjects activated by stimuli through bone-conducted ultrasonic, air-conducted, bone-conducted, and vibro-tactile hearing aids. All of the hearing aids, including the ultrasonic hearing aid, consistently activated the medial portion of the primary auditory cortex of the normal volunteers. The same cortical area was also significantly activated in the profoundly deaf subjects although the percentage increase in regional cerebral blood flow (rCBF) was smaller than in normal subjects. These results suggest that extra-cochlear routes convey information to the primary auditory cortex and can therefore produce detectable sound sensation even in the profoundly deaf subjects, who reported a sensation themselves.

Adult↗

WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain.

Wolfram (DIDMOAD) syndrome is an autosomal recessive neurodegenerative disorder accompanied by insulin-dependent diabetes mellitus and progressive optic atrophy. Recent positional cloning led to identification of the WFS1 (Wolfram syndrome 1) gene, a member of a novel gene family of unknown function. In this study, we generated a specific antibody against the C-terminus of the WFS1 protein and investigated its subcellular localization in cultured cells. We also studied its distribution in the rat brain. Biochemical studies indicated the WFS1 protein to be an integral, endoglycosidase H-sensitive membrane glycoprotein that localizes primarily in the endoplasmic reticulum (ER). Consistent with this, immunofluorescence cell staining of overexpressed WFS1 showed a characteristic reticular pattern over the cytoplasm and overlapped with the ER marker staining. No co-localization of WFS1 with mitochondria argues against an earlier clinical hypothesis that Wolfram syndrome is a mitochondria-mediated disorder. In the rat brain, at both the protein and mRNA level, WFS1 was found to be present predominantly in selected neurons in the hippocampus CA1, amygdaloid areas, olfactory tubercle and superficial layer of the allocortex. These expression sites, i.e. components of the limbic system or structures closely associated with this system, may be involved in the psychiatric, behavioral and emotional abnormalities characteristic of this syndrome. ER localization of WFS1 suggests that this protein plays an as yet undefined role in membrane trafficking, protein processing and/or regulation of ER calcium homeostasis. These studies represent a first step toward the characterization of WFS1 protein, which presumably functions to maintain certain populations of neuronal and endocrine cells.

Animals↗

New epidermal keratin genes from Xenopus laevis: hormonal and regional regulation of their expression during anuran skin metamorphosis.

Xenopus larval keratin (XLK) was isolated by gel electrophoresis of proteins of tadpole skin. Screening of an expression cDNA library of tail tissues by specific polyclonal antibodies against XLK produced XLK cDNA (xlk). Its complete nucleotide and predicted amino acid sequences revealed that XLK was a new member of type II keratin. Screening of a cDNA library of adult Xenopus skin using an oligonucleotide probe which had been designed from well-conserved N-terminal amino acid sequences of the rod domain of type I keratin produced two cDNAs, xak-a and xak-b, which were found to be new members of type I keratin gene. Northern blot analysis showed that xlk was expressed exclusively in the larval skin whereas xak-a and xak-b were expressed exclusively in the adult skin. Their expression level was regulated in a region- and metamorphic stage- dependent manner during larval skin development. mRNA in situ hybridization experiments identified the cells that expressed xlk, and xak-a and xak-b as larva- specific epidermal cells (skein cells and basal cells), and adult suprabasal epidermal cells, respectively. These three genes were found to be late responsive to thyroid hormone. Phylogenetic relationships of these keratins with known ones are discussed.

Amino Acid Sequence↗

Molecular engineering of myoglobin: the improvement of oxidation activity by replacing Phe-43 with tryptophan.

The F43W and F43W/H64L myoglobin (Mb) mutants have been constructed to investigate effects of an electron rich oxidizable amino acid residue in the heme vicinity on oxidation activities of Mb. The Phe-43 --> Trp mutation increases the rate of one-electron oxidation of guaiacol by 3-4-fold; however, the peroxidase activity for F43W/H64L Mb is less than that of the F43W single mutant because the absence of histidine, a general acid-base catalyst, in the distal heme pocket suppresses compound I formation. More than 15-fold improvement versus wild-type Mb in the two-electron oxidation of thioanisole and styrene is observed with the Phe-43 --> Trp mutation. Our results indicate that Trp-43 in the mutants enhances both one- and two-electron oxidation activities (i.e., F43W Mb > wild-type Mb and F43W/H64L Mb > H64L Mb). The level of (18)O incorporation from H2(18)O2 into the epoxide product for the wild type is 31%; however, the values for F43W and F43W/H64L Mb are 75 and 73%, respectively. Thus, Trp-43 in the mutants does not appear to be utilized as a major protein radical site to form a peroxy protein radical in the oxygenation. The enhanced peroxygenase activity might be explained by the increase in the reactivity of compound I. However, the oxidative modification of F43W/H64L Mb in compound I formation with mCPBA prevents us from determining the actual reactivity of the catalytic species for the intact protein. The Lys-C achromobacter digestion of the modified F43W/H64L mutant followed by FPLC and mass analysis shows that the Trp-43-Lys-47 fragment gains a mass by 30 Da, which could correspond two oxygen atoms and loss of two protons.

Amino Acid Substitution↗

Pre-meiotic S phase is linked to reductional chromosome segregation and recombination.

Meiosis is initiated from G1 of the cell cycle and is characterized by a pre-meiotic S phase followed by two successive nuclear divisions. The first of these, meiosis I, differs from mitosis in having a reductional pattern of chromosome segregation. Here we show that meiosis can be initiated from G2 in fission yeast cells by ectopically activating the meiosis-inducing network. The subsequent meiosis I occurs without a pre-meiotic S phase and with decreased recombination, and exhibits a mitotic pattern of equational chromosome segregation. The subsequent meiosis II results in random chromosome segregation. This behaviour is similar to that observed in cells lacking the meiotic cohesin Rec8 (refs 3, 4), which becomes associated with chromosomes at G1/S phase, including the inner centromere, a region that is probably critical for sister-centromere orientation. If the expression of Rec8 is delayed to S phase/G2, then the centromeres behave equationally. We propose that the presence of Rec8 in chromatin is required at the pre-meiotic S phase to construct centromeres that behave reductionally and chromosome arms capable of a high level of recombination, and that this explains why meiosis is initiated from G1 of the cell cycle.

Chromosome Segregation↗

Effects of stimulus presentation rate on the activity of primary somatosensory cortex: a functional magnetic resonance imaging study in humans.

To investigate the effect of stimulus presentation rate on the activity of primary somatosensory cortex, we performed echo-planar functional magnetic resonance imaging using a 1.5-tesla magnetic resonance system. Eight right-handed normal volunteers underwent functional magnetic resonance imaging during somatosensory stimulation with a 0.2 ms electrical square wave to the left index finger at 1, 4, 8, 16, and 32 Hz at constant intensity. Activated areas were located mainly around 'the hand area' of the right postcentral gyrus. Between 4 and 16 Hz, almost all subjects showed significant activation, but at 1 Hz and 32 Hz, five of eight subjects showed no activation. The average number of activated pixels in this area between 4 and 16 Hz were significantly greater than those at 1 Hz and 32 Hz, and the average percent signal increase had its activation peak at 8 Hz. Our results suggest that the existence of the optimal stimulation rate range may be a common phenomenon to a variety of sensory modalities. The electrical somatosensory stimulation rates from 4 Hz to 16 Hz are advisable to investigate the activation of the primary somatosensory cortex in human subjects.

Adult↗

Surface conduction on insulating BaTiO3 crystal suggesting an intrinsic surface electron layer.

We report conduction measurements on the clean, free surface of transparent insulating BaTiO3 single crystals in high vacuum. We find that the insulating BaTiO3 crystals exhibit surface conductance that is dependent on the spontaneous polarization, whereas no conduction perpendicular to the surface is observed. The surface conduction shows semimetallic temperature dependence and persists down to at least 100 K. The observations suggest a two-dimensional electron on a clean, free ferroelectric surface that may be regarded as a ferroelectric metal. The results have important implications for understandings of the fundamental properties of ferroelectrics, the size effect, and ferroelectric devices.

Journal Article↗

Surgical technique for combined intestine-auxiliary liver transplantation in rats: development of a new microsurgical model.

Combined liver-intestine transplantation is an evolving procedure, and auxiliary liver transplantation has several advantages over standard orthotopic liver transplantation. We present a new model of combined intestine-auxiliary liver transplantation in rats. Total small bowel and 60% liver were harvested en bloc. An aortic segment that contained the celiac axis and superior mesenteric artery ensured blood supply to the graft. Venous drainage of the grafted intestine was achieved via the intact portal vein of the graft. The infrahepatic vena cava was cut at different levels during the modification period and at the oblique level of the left renal vein in consecutive series. Revascularization was accomplished by end-to-side anastomosis of the aorta and of the infrahepatic vena cava. The recipient small bowel was resected and the intestine continuity restored by anastomosis. Total operation time averaged 130 min. The overall survival rate of 3 months in the consecutive series was 80% (16/20). Exploratory laparatomy and histologic study in 3 rats on 90 days after transplantation revealed normal and viable grafts. Liver function was normal and both grafted liver and intestine showed normal histologic architectures in 5 rats observed for 12 months after transplantation. The present model is reproducible and allows preclinical research on several aspects of experimental combined intestine-auxiliary liver transplantation.

Animals↗