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Biomedical subjects

I Saitoh

Publications and source records attributed to I Saitoh.

28 records · Page 2Linked to original sources

Fission yeast genes nda1+ and nda4+, mutations of which lead to S-phase block, chromatin alteration and Ca2+ suppression, are members of the CDC46/MCM2 family.

Fission yeast cold-sensitive mutants nda1-376 and nda4-108 display a cell cycle block phenotype at the restrictive temperature (cell elongation with the single nucleus) accompanied by an alteration in the nuclear chromatin region. DNA content analysis shows that the onset of DNA synthesis is blocked or greatly delayed in both mutant cells, the block being reversible in nda4-108. Upon release to the permissive temperature, nda4-108 cells resumed replicating DNA, followed by mitosis and cytokinesis. The nda4 phenotype was partly rescued by the addition of Ca2+ to the medium; Ca2+ plays a positive role in the nda4+ function. The predicted protein sequences of nda1+ and nda4+ isolated by complementation are similar to each other and also, respectively, to those of the budding yeast, MCM2 and CDC46, both of which are members of the gene family required for the initiation of DNA replication. The central domains of these proteins are conserved, whereas the NH2- and COOH- domains are distinct. Results of the disruption of the nda1+ and nda4+ genes demonstrates that they are essential for viability.

Amino Acid Sequence↗

Comparison of structure of quinone redox site in the mitochondrial cytochrome-bc1 complex and photosystem II (QB site).

A series of nitrophenolic electron-transport inhibitors (2-substituted 4,6-dinitrophenols) of rat liver mitochondrial cytochrome-bc1 complex and of photosystem II (QB site) of spinach thylakoids was synthesized. The structure/inhibitory-activity relationship was examined to elucidate differences in the three-dimensional structure of the quinone redox site in the two systems. These inhibitors occupy the ubiquinone redox site of cytochrome-bc1 complex competitively with natural ubiquinol, probably at a Qo reaction center. The inhibitory activity tended to increase with the length of the 2-substituent, which may correspond to the isoprenoid side chain of ubiquinone and plastoquinone, increased in both experimental systems. However, the strict structural requirements of the 2-substituent for binding to the ubiquinone or plastoquinone redox site were not identical. The alkyl substituents with a branching structure at the alpha-position to the benzene ring were favorable for inhibition of the cytochrome-bc1 complex, but not of photosystem II. Molecular-orbital calculations indicated that the main chain of 2-substituents with an alpha-branching structure was almost perpendicular to the benzene-ring plane because of steric congestion between the alpha-methyl and phenolic OH groups. The main chain of 2-substituents without an alpha-branching structure was flexible. Molecular-orbital studies indicated that ubiquinol was most stable when the portion of the isoprenoid side chain adjacent to the quinol ring was perpendicular to the quinol-ring plane, because of steric congestion by the vicinal OH and methyl groups. The side chain of plastoquinol was flexible because of the lack of a vicinal methyl group. Thus, the difference in the inhibitory activities between the two systems seemed to reflect the difference in the configuration of the isoprenoid side chain of ubiquinone and plastoquinone. These results suggested that the quinone redox site of the cytochrome-bc1 complex may recognize the configuration of the side chain near the quinone ring in the strict sense, whereas that of photosystem II (QB site) may recognize it in a loose sense.

Animals↗

Inhibition of electron transport of rat liver mitochondria by unnatural (-)-antimycin A3.

The inhibition of electron transport by unnatural (-)-antimycin A3 was examined with rat liver mitochondria and compared with that of natural (+)-antimycin A3. (-)-Antimycin A3 inhibited respiration about 1/100th as strongly as natural (+)-antimycin A3. (-)-Antimycin A3 binding to the cytochrome bc1 complex did not seem to induce a conformational change in this proteinous complex. The binding site of (-)-antimycin A3 was probably the same as that of (+)-antimycin A3 (at the Qi center). However, the mode of interaction with the Qi center by (-)-antimycin A3 and (+)-antimycin A3 was somewhat different.

Animals↗

[Release of endothelin from isolated perfused human umbilical vein. I: Effect of ionomycin].

Endothelin-like immunoreactivity (ET-LI) was directly measured in the perfusate from the isolated human umbilical vein perfused with Krebs-Ringer solution. The identity of the immunoreactive peptide was confirmed as ET-1 by high-performance liquid chromatography. The rate of release of ET-LI was 86.7 +/- 25.9 (SE) fmol during the first perfusion period of 30 min, and it remained stable at least for 4 hours. Calcium ionophore ionomycin, added to the perfusion medium (10(-7)-10(-6) M), stimulated the ET-LI release in a dose-dependent fashion; it increased the rate of release by 29.1% and 143.4% over the control at the concentrations of 10(-7) and 10(-6) M, respectively. These results taken together with previous observations of synthesis of ET in cultured vascular endothelium provide direct evidence for local generation and subsequent release of ET from vascular beds of human beings.

Calcium↗

[An immunohistochemical study on the response of nerve fibers in the periodontium of rat molars during experimental tooth movement].

It is well known that orthodontic forces induce pain during tooth movement. However there have been few neurohistological studies on sensational periodontal tissue response to orthodontic tooth movement. So we have many unknown problems about reactions of periodontal nerve fibers during tooth movement. The present study deals with the response of nerve fibers in periodontal ligament of rat molar during experimental tooth movement by means of immunohistochemical method for calcitonin gene-related peptide (CGRP). The results obtained in this study were as follows: 1. In control sections, CGRP-immunopositive nerve fibers were observed both around the root apex and in the intermediate region of the periodontal ligament. Although most of those fibers was distributed around the blood vessels, a few nerves were recognized to terminate in the periodontal fibers. 2. At three days after tooth movement, the CGRP-positive nerves gradually increased in number around the blood vessels. After that, the number of CGRP-positive nerves decreased and no difference of distribution of CGRP-positive nerves was observed between the control sections and the experimental sections at seven days. 3. Especially, at three days when active remodeling of alveolar bone was taking place, a few nerve fibers showing CGRP-immunoreactivity were observed to concentrate around osteoclasts or to migrate Howship's lacunae. These findings showed the dynamic changes of CGRP-immunoreactive nerves in the periodontal ligament during tooth movement, and suggested that this reaction of the periodontal nerves might induce pain in patients. In addition to neurotransmitter function, it was supposed that CGRP directly or indirectly effected the cellular elements and surrounding tissues on peripheral organs such as vascular system and osteoclasts.

Animals↗

[Study on the simulation in planning for orthognathic surgery by using a personal computer].

This study was made in order to develop and evaluate three-dimensional simulation programs in planning for orthognathic surgery by using microcomputer system. Microcomputer system is composed of CPU (NEC, PC-9801), high resolutional color display, color printer, image scanner, and MOUSE. This simulation is composed of four procedures. 1. Data input Three-dimensional coordinate data on tracing obtained from CT films is inputted. One data file is made from one outline of structures. 2. Three dimensional reconstruction A control file is made to arrange data files constructing structures. 3. Simulation This procedure is composed of cutting and movement. The horizontal projection of mandible is displayed. After cutting simulated orthognathic surgery is designed, new data files and new control file are made. A movement consists of parallel translation and rotation. A movement data is combined with movements designed on each of three projections. 4. Three-dimensional graphic display Three-dimensional graphics of the mandible before and after a simulation for orthognathic surgery are displayed by perspective views with treated hidden lines and accurate pictures (COSMOZONE 2SA, NIKON). These simulation programs were carried out with the asymmetrical patient. The simulation was supposed that the operation was combined with sagittal splitting osteotomy of the right mandibular ramus and body ostectomy of the left lower first premolar part. Three-dimensional graphics of the mandible before and after the simulation were presented. Its three-dimensional mandibular position and form after orthognathic surgery were predicted. These three-dimensional simulation programs may be important procedure, when a treatment planning in asymmetrical prognathic case is discussed.

Computer Graphics↗

Correlation of detectability of hepatitis C virus genome in saliva of elderly Japanese symptomatic HCV carriers with their hepatic function.

The hepatitis C virus (HCV) genome was sought in the saliva of 76 chronic HCV carriers (mean age nearly 60 years) in a rural Japanese town, who had high serum titers of c-100 and anti-core second generation antibodies. In 27 samples (27 cases, 36%), the HCV-RNA genome was detected by the reverse transcriptase - polymerase chain reaction with either of two sets of primers covering two regions of the HCV genome: the 5'noncoding region and the region encompassing the putative envelope (E1). Transaminase values at the time of sampling were higher in the patients with than in those without detectable HCV RNA in saliva (p = 0.04 for alanine aminotransferase, p = 0.04 for aspartate aminotransferase; Wilcoxon test). The prevalence of the positivity was higher by 5'noncoding primers (14/59 vs. 15/68). Our data show that the severity and duration of hepatic dysfunction influence the detectability of the HCV genome in the saliva. This has been a controversial point among investigators.

Adult↗

Inhibition of migrating lens epithelial cells by blocking the adhesion molecule integrin: a preliminary report.

PURPOSE: To evaluate the preventive effect of blocking integrins by sustained release of RGD peptide (arginine-glycin-aspartic acid sequence) or a combination of RGD peptide and ethylenediaminotetraacetic acid (EDTA) on lens epithelial cell (LEC) migration. SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHOD: A polylactic-glycolic acid disk containing 4% RGD or a combination of 23% EDTA and 10% RGD was implanted in the capsular bag in five rabbit eyes following standard cataract surgery. The release rate in vitro was 4.4 microg/h for RGD peptide alone and 7.8 and 7.6 microg/h for combined EDTA and RGD peptide, respectively. The contralateral eye received a disk without agents as a control. RESULTS: After 1 month, a slight inhibition of LEC migration onto the posterior capsule was observed histopathologically in eyes receiving RGD peptide. A significant inhibition was observed in eyes with combined EDTA and RGD. CONCLUSIONS: Application of RGD peptide and EDTA and RGD peptide may inhibit LEC migration by inhibiting the integrins expressed on the LECs. Blocking adhesion molecules expressed on LECs may reduce posterior capsule opacification.

Animals↗