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Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 469 records · Page 26Linked to original sources

Fission yeast Nda1 and Nda4, MCM homologs required for DNA replication, are constitutive nuclear proteins.

The nda1+ and nda4+ genes of the fission yeast Schizosaccharomyces pombe encode proteins similar to budding yeast MCM2 and MCM5/CDC46, respectively, which are required for the early stages of DNA replication. The budding yeast Mcm proteins display cell-cycle dependent localization. They are present in the nucleus specifically from late M phase until the beginning of S phase, so that they were suggested to be components of a replication licensing factor, a positive factor for the onset of replication, which is thought to be inactivated after use, thus restricting replication to only once in a cell cycle. In the present study, we raised antibodies against Nda1 or Nda4 and identified 115 kDa and 80 kDa proteins, respectively. Their immunolocalization was examined in wild-type cells and in various cell-cycle mutants. Both Nda1 and Nda4 proteins remained primarily in the nucleus throughout the cell cycle. In mutants arrested in G1, S, and G2 phases, these proteins were also enriched in the nucleus. These results indicate that the dramatic change in subcellular localization as seen in budding yeast is not essential in fission yeast for the functions of Nda1 and Nda4 proteins to be executed. The histidine-tagged nda1+ gene was constructed and integrated into the chromosome to replace the wild-type nda1+ gene. The resulting His-tagged Nda1 protein was adsorbed to the Ni-affinity column, and co-eluted with the untagged Nda4 protein, suggesting that they formed a complex.

Animals↗

Signal transduction pathway on beta-glucans-triggered hydrogen peroxide production by murine peritoneal macrophages in vitro.

It has been reported that the biological activities of several beta-glucans vary due to differences in their physicochemical properties. In this study we investigated the ability of beta-glucans to trigger H2O2 production and activate signaling pathway on peritoneal macrophages. The most effective beta-glucan tested on H2O2 production was zymocel which was a particulate preparation from the yeast cell wall. In contrast, gel-forming beta-glucans which are known as immunoenhancers did not trigger the H2O2 production by macrophages at all. To identify the related signaling pathway for the particulate beta-glucans-triggered H2O2 production, several inhibitors were applied. Hydrogen peroxide production triggered with phorbol myristate acetate was inhibited by pretreatment of macrophages with H-7, a protein kinase C inhibitor. However, beta-glucans-triggered H2O2 production was not affected by H-7. The results suggested that genistein-sensitive tyrosine kinase and bromophenacyl bromide-sensitive phospholipase A2 participated in the particulate beta-glucans-triggered H2O2 production, although the phagocytosis of particulate beta-glucans was not inhibited by either reagents. In conclusion, gel-forming (1-->3)-beta-D-glucans-induced activation was not sufficient to trigger H2O2 on macrophages, and pathways for particulate beta-glucans-triggered H2O2 production were regulated differently from those for phagocytosis of beta-glucans.

Animals↗

Effect of beta-glucans on the nitric oxide synthesis by peritoneal macrophage in mice.

Nitric oxide (NO) is an important effector molecule on antimicrobial and antitumor effects of macrophages. (1 -> 3)-beta-D-Glucan (beta-glucan) is well known to show various immunopharmacological effects such as antimicrobial effect and antitumor effect by activating various points of host defense mechanisms. This paper deals with NO synthetic activity of peritoneal macrophage (PM) induced by beta-glucan administration in mice. The activity was determined by measuring NO concentration in PM culture by Griess reagent after 24 or 48 h in vitro culture. Administration (i.p. or i.v.) of a branched soluble (1 -> 3)-beta-D-glucan, grifolan (GRN), from Grifola frondosa enhanced NO synthesis of PM dose and time dependently. The activity was abrogated by the addition of N(G)-monomethyl-L-arginine (L-NMMA) in vitro. The most significant activity was observed at 3-7 d after the administration of GRN (250 mu g/mouse). PM from all strains of ICR, C3H/HeN, C3H/HeJ, BALB/c, BALB/c nu/nu, C57BL, and AKR mice showed significant activity by GRN administration. Among beta-glucans tested, SSG and OL-2, highly branched soluble glucans, and a particulate beta-glucan, zymosan, showed similar activity. Addition of GRN directly to in vitro RAW 264.7 or proteose peptone induced peritoneal macrophage (PP-PEC) culture could not enhance NO synthesis. However, NO synthesis of PP-PEC was enhanced in vitro by addition of GRN in the presence of interferon gamma (IFN gamma). Gene expression of IFN gamma mRNA in the liver and PEC were enhanced in GRN administered mice assessed by reverse transcriptase assisted PCR (RT-PCR) method. These facts strongly suggested that beta-glucan has capacity to enhance NO synthesis of PM in vivo through IFN gamma mediated mechanism.

Adjuvants, Immunologic↗

Characterization of sodium hypochlorite degradation of beta-glucan in relation to its metabolism in vivo.

Soluble (SSG, beta-1,3-D-glucan obtained from the culture filtrates of a fungus, Sclerotinia sclerotiorum IFO 9395) and particulate (zymosan) beta-glucans were oxidized by sodium hypochlorite (NaClO), and the oxidized products were analyzed by gel filtration and ion-exchange chromatographies and by limulus G-test to study the metabolism of beta-glucans in vivo. By oxidative degradation, SSG was gradually oxidized to anionic polymers, which decreased the molecular weight and reduced the content of the sidechain at the same time. Zymosan, a particle from fungi cell wall, was easily solubilized to a high molecular weight polysaccharide by oxidative degradation. The elution profiles on ion exchange columns and the limulus G-test reactivity of the products were similar to those of polysaccharides obtained by in vivo experiments using SSG and zymosan. These results suggest that oxidative degradation is the main metabolic pathway of beta-glucans in vivo, and that the sidechains would be oxidized faster than the main chain.

Ascomycota↗

Expression of CD45-restricted form B in (NZW x BXSB) F1 and MRL/Mp-lpr/lpr mice.

Expression of CD45RB on CD4+ or CD8+ cells in combination with TCRV beta usages (V beta 6, V beta 8.1, V beta 8.2, V beta 11 and V beta 17a) in normal mouse strains (BALD/c and C57BL/6) was compared with autoimmune-prone strains (NZW x BXSB) F1 and MRL/lpr) at young and old ages. The frequencies, and also the numbers of CD45RB- cells in CD4+ T cells with various TcR repertoires was significantly less in the autoimmune-prone stains at old ages, while, in normal control strains, they remained unchanged. Furthermore, CD4+/CD45RB- cells are CD44high and CD62L (L- selectin).low These findings suggest that most T cells, especially CD4+ T cells, in old W/BF1 and old MRL/lpr mice, were activated and this may reflect the elevation of autoantibodies and the progress of autoimmune status in aged autoimmune-prone mice. This will be discussed in relation to the progress of the autoimmune diseases.

Aging↗

[Advances in the treatment of colorectal cancer].

Colorectal cancer is one of the most serious diseases of our time. Recent progress in its treatment is reviewed in this paper. There are many approaches for treating colorectal cancer; extended surgery to function-preserving surgery. The aim of surgical treatment is to excise the tumor completely, so extended surgery has been performed for curative resection of colorectal cancer. However, the quality of life (QOL) of the patients has been extremely impaired. In recent years, surgical treatments for avoiding colostomy, and urinary and sexual difficulties have been widely carried out, and QOL of the patients could be maintained in the postoperative period. Stage-oriented therapy is accepted as the concept of surgical treatment of colorectal cancer. For further improving the clinical results of colorectal cancer, we advocated "type-oriented therapy" which is based on the biological characteristics of colorectal cancer, by determining i.e., p53 abnormalities of cancer cells, serum p53 antibodies, micrometastasis in the bone marrow and/or sensitivity to anticancer drugs.

Antineoplastic Combined Chemotherapy Protocols↗

[Hepatic metabolism and transport of bilirubin and other organic anions].

Most of bilirubin, bile acids and other organic anions are preferentially taken up by the liver and excreted into bile. Recently many transporters on the sinusoidal and canalicular membranes of the hepatocytes have been reported for each ligand. complementary DNA was cloned for human Na+/taurocholate cotransporting polypeptide (NTCP) which mediates sodium dependent secondary active hepatic uptake of bile acids. For the hepatic uptake of non-bile acid-organic anions such as bilirubin, at least 4 transporters are postulated, i.e., bilirubin/BSP binding protein (BBBP), organic anion binding protein (OABP), bilitranslocase, and organic anion transporting polypeptide (OATP). In the hepatocytes, bilirubin is glucuronidated in the endoplasmic reticulum. The gene for UDP-glucuronosyltransferase (UGT) 1 family has been elucidated and differential splicing from several exons 1 (A to J) results in forming isozymes of UGT 1 including bilirubin UGT. At the canalicular membranes, two main ATP-dependent organic anion transporters have been reported, i.e., canalicular bile salt transporter (cBST) for bile acids and canalicular multispecific organic anion transporter (cMOAT) for non-bile acid organic anions. Recently multidrug resistance protein (MRP) is reported closely related to or identical to cMOAT. These canalicular ATP-dependent transporters are called ABC (ATP-binding cassette) transporters.

Animals↗

[Intrahepatic cholestasis].

Various effects of cholestatic drugs, bile acids, and estrogens on the hepatocyte plasma membranes, as well as their changes in the cholestatic diseases are briefly reviewed. Cyclosporin A inhibits bile salt transporter (BST) on the canalicular membrane (CM). Ethynylestradiol reduces canalicular glutathione excretion. Estradiol-17beta-D-glucuronide interacts with MDR1, and taurochenodeoxycholic acid and lithocholate-3-O-glucuronide may interact with vesicular transport system, each of which may relate with the genesis of cholestasis. In Byler disease, biliary chenodeoxycholic acid excretion is defective. Lipopolysaccharide decreases the function of canalicular multispesific organic anion transporter (MOAT) which seems the first step in septic cholestasis. Obstructive jaundice causes reduced activity of both canalicular BST and MOAT. The mechanisms of choleretic action of S-adenosylmethionine and other drugs are also reviewed.

Animals↗

[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors].

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.

Adult↗

Postoperative bile peritonitis caused by division of an aberrant bile duct in the left triangular ligament of the liver.

A 61-yr-old man underwent Billroth I gastrectomy for an advanced cancer in the corpus of the stomach. On the first postoperative day, fresh bile discharged from the penrose drains, which had been placed in Winslow's foramen, and the volume of bile discharge subsequently increased. Leakage from the gastroduodenal anastomosis was excluded by gastroduodenography. Exploratory relaparotomy showed bile peritonitis with much more bile retention in the left subphrenic space. The origin of bile leakage could not be traced despite close examination of all the extrahepatic biliary tract and the liver surface. Intraoperative cholangiography through the cystic duct after cholecystectomy revealed that the bile leakage originated from an aberrant bile duct present in the free edge of the left triangular ligament (appendix fibrosa hepatis), which had been unintentionally cut at the primary operation. Knowledge of this anatomical structure is important and proper ligation is recommended when dissecting the appendix fibrosa hepatis to avoid postoperative bile peritonitis and the need for a relaparotomy.

Bile↗

Functioning survival rate of fixtures and superstructures of osseointegrated implants: ten years of progress in Tokyo Dental College Hospital (second report).

Osseointegrated implant bridges (OIB) have shown excellent results in the majority of cases. Since 1983, 1,022 fixtures has been applied to 241 superstructures in Tokyo Dental College Hospital. The aim of present study was to examine their functioning survival rate during recent ten years. The functioning survival rate of the superstructure of OIB has been almost 100% in both maxilla and mandible. Although 13.0% of these fixtures had to be removed in maxillary complete cases, only 3.3% of fixtures were removed in other cases. In maxillary complete cases, the functioning survival rate of OIB fixtures gradually decreases from 91% to 74% (91%, less than 3 years; 84%, between 3 and 7 years; 74%, more than 7 years), but it remained at about 97% for all periods in other cases. Apparently, the functioning survival rate of OIB fixture is generally determined within the period of one year, so almost the same rate is maintained thereafter. It is suggested that if more fixture numbers in the superstructure were applied to maxillary complete cases, the functional survival rate might improve.

Adolescent↗

Binding of human prothymosin alpha to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev.

Rex of human T-cell leukemia virus type I (HTLV-I) and Rev of human immunodeficiency virus 1 (HIV-1) are post-transcriptional regulators of viral gene expression. By means of affinity chromatography, we purified an 18-kDa cellular protein that bound to the conserved leucine-motif/activation domain of HTLV-I Rex or HIV-1 Rev. The protein that was purified through a Rev-affinity column was found to bind to Rex immunoprecipitated with anti-Rex IgG from an HTLV-I-producing cell line. We analyzed the purified approximately 18-kDa protein biochemically and identified it as prothymosin alpha. The binding activity of prothymosin alpha to Rev or Rex was completely abolished when the epsilon-amino groups of its lysine residues were chemically modified by N-succinimidyl-3-(4-hydroxy-3,5-diodo- phenyl)propionate. The functional relationship between the nuclear protein prothymosin alpha and Rex-Rev is discussed.

Amino Acid Sequence↗

Origin of the nitrogen atom of pyridoxine in Saccharomyces cerevisiae.

The origin of the nitrogen atom of pyridoxine was studied in Saccharomyces cerevisiae. The 15N atom of 15NH4Cl added to the growth medium as the nitrogen source was incorporated efficiently into the nitrogen atom of pyridoxine. The competitive effects of 14N-amino acids on the incorporation of 15NH4Cl were examined. Incorporation of 15N into pyridoxine was inhibited by glutamine. The label of L-[amide-15N]glutamine was incorporated effectively into pyridoxine in S. cerevisiae. On the other hand, the label from L-[amide-15N]glutamine was not incorporated into pyridoxine in Escherichia coli. These findings suggest that the biosynthetic pathway of pyridoxine in S. cerevisiae differs from that in E. coli.

Escherichia coli↗