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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 379 records · Page 21Linked to original sources

Total synthesis of globotriaosyl-E and Z-ceramides and isoglobotriaosyl-E-ceramide.

Stereoselective, total synthesis of O-alpha-D-galactopyranosyl-(1----4) -O-beta-D-galactopyranosyl-(1----4)-O-beta-D-glucopyranosyl-(1----1)-N -tetracosanoyl-[2S,3R,4E (and 4Z)]-sphingenine and O-alpha-D -galactopyranosyl-(1----3)-O-beta-D-galactopyranosyl-(1----4)-O-beta-D -glucopyranosyl-(1----1)-N-tetracosanoyl-(2S,3R,4E)-sphin gen ine was achieved by using O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl) -(1----4)-O-(2,3,6-tri-O-acetyl-beta-D-galactopyranosyl)-(1----4)-2,3,6- tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate, O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl) -(1----4)-O-(2,3,6-tri-O-acetyl-beta-D-galactopyranosyl)-(1----4)-2,3,6- tri-O-acetyl-alpha (and beta)-D-glucopyranosyl fluoride, and O-(2,3,4,6-tetra-O-acetyl-alpha-D -galactopyranosyl)-(1----3)-O-(2,3,6-tri-O-acetyl-beta-D-galactopyran osyl)-(1----4)-2,3,6-tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate.

Carbohydrate Conformation↗

Total synthesis of sialosylcerebroside, GM4.

Described are total syntheses of O-[sodium (5-acetamido-3,5-dideoxy-D -glycero-alpha-D-galacto-2-nonulopyranosyl)onate]-(2----3)-O -beta-D -galactopyranosyl-(1----1)-(2R,3S,4E)-2-N-tetracosanoylsphingen ine,O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl+ ++)onate] -(2----3)-O-alpha-D-galactopyranosyl-(1----1)-(2R,3S,4E)-2-N -tetracosanoylsphingenine, O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-beta -D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-beta-D-gal act opyranosyl -(1----1)-(2R,3S,4E)-2-N-tetracosanoylsphingenine, and O-[sodium (5-acetamido-3,5-dideoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl++ +)onate] -(2----3)-O-alpha-D-galactopyranosyl-(1----1)-(2R,3S,4E)-2-N -tetracosanoylsphingenine by using O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D -galacto-2-nonulopyranosyl)onate]-(2----3)-2,3,4,6-tetra-O-a cetyl-D -galactopyrano-syl trichloroacetimidate and O-[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-beta -D-galacto-2-nonulopyranosyl)onate]-(2----3)-2,4,6-tri-O-ace tyl-D-galactopyranosyl trichloroacetimidate as key glycosyl donors, and (2S,3R,4E)-3 -O-benzoyl-2-N-tetracosanoylsphingenine as a key glycosyl acceptor.

Carbohydrate Conformation↗

Immunological aspects of the anemia of rheumatoid arthritis.

In order to investigate the cause of the anemia concomitant with rheumatoid arthritis (RA), we examined, using the erythroid colony assay of human bone marrow colony-forming units-erythroid (CFU-e) and burst-forming units-erythroid (BFU-e), the effects of the patients' serum and peripheral blood T lymphocytes on the CFU-e-derived colonies. The counts of erythroid colonies of RA patients were markedly lower than those of human control subjects [CFU-e: control 152.9 +/- 30.6 (n = 19), RA 51.1 +/- 13.6 (n = 7), t = 7.66567, p less than 0.01; BFU-e: control 25.2 +/- 5.9 (n = 5), RA 12.6 +/- 2.6 (n = 7), t = 4.574, p less than 0.01]. The serum from two out of seven RA patients slightly inhibited the formation of CFU-e-derived colonies of human control subjects (t = 2.31, 0.05 less than p less than 0.1); however, the serum from the other five RA patients did not significantly inhibit human control erythroid colony formation as compared with human control serum (t = 0.981, 0.3 less than p less than 0.4). On the other hand, peripheral blood T lymphocytes of the patients markedly inhibited the formation of CFU-e-derived colonies of the control subjects as compared with peripheral blood T lymphocytes from human control subjects (t = 4.24, p less than 0.01). The above-mentioned results suggest that the peripheral blood T lymphocytes of RA patients might play a role as one of the causes of the concomitant anemia of RA patients.

Adult↗

Effect of the recombinant vaccinia viruses that express HTLV-I envelope gene on HTLV-I infection.

The human T-lymphotropic virus type I (HTLV-I) is etiologically linked to adult T-cell leukemia (ATL). To develop a vaccine against ATL, we constructed recombinant vaccinia viruses containing the envelope gene of HTLV-I in the vaccinia virus hemagglutinin (HA) gene, a new site where foreign genes can be inserted. A single inoculation of the recombinant virus induced antibodies to the env proteins of HTLV-I in rabbits and had a protective effect against HTLV-I infection.

Animals↗

Nucleotide sequencing analysis of a LEU gene of Candida maltosa which complements leuB mutation of Escherichia coli and leu2 mutation of Saccharomyces cerevisiae.

The expression of a LEU gene from Candida maltosa (designated as C-LEU2) isolated previously (Kawamura et al. 1983) was shown to be regulated, when transferred into Saccharomyces cerevisiae, by leucine and threonine in the medium, as in the case of LEU2 gene of S. cerevisiae. The coding region together with the regulatory region was subcloned and the nucleotide sequence was determined. When the sequence of the coding region was compared with that of LEU2, the homology was 72% for base pairs and 76% for deduced amino acids. Comparison of the regulatory region of C-LEU2 with those of LEU1 and LEU2 suggested a few short consensus sequences which are involved in regulation of gene expression by leucine and threonine in the medium.

3-Isopropylmalate Dehydrogenase↗

Recombinant vaccinia virus LC16m0 or LC16m8 that expresses hepatitis B surface antigen while preserving the attenuation of the parental virus strain.

Thymidine kinase-negative recombinant vaccinia virus LC16m0 or LC16m8 expressing hepatitis B surface antigen preserved almost the same pathogenicity as their parental thymidine kinase-positive attenuated virus strains. The results demonstrate the potential for using the LC16m0 or LC16m8 virus strain as a vector for recombinant vaccine.

Animals↗

Genetic analysis of vaccinia virus Lister strain and its attenuated mutant LC16m8: production of intermediate variants by homologous recombination.

We prepared vaccinia virus variants by introducing part of the HindIII D fragment of the DNA of the parental Lister (LO) strain (temperature-resistant and forming large plaques and pocks) into the attenuated LC16m8 strain (temperature-sensitive and forming small plaques and pocks) by the use of a homologous recombination technique in vivo. Special attention was paid to the HindIII D fragment, since this fragment has an extra XhoI site in LC16m8 which is absent from LO. After HindIII D of LO was introduced as a calcium phosphate precipitate into rabbit kidney (RK13) cells which had been infected with LC16m8, five virus variants (LOTC-1 to LOTC-5) forming much larger plaques than LC16m8 were cloned. In LOTC-2, LOTC-4 and LOTC-5, the introduction of at least part of HindIII D of LO into the corresponding HindIII D region of the LC16m8 genome was apparent as judged by the disappearance of the XhoI site, whereas variants LOTC-1 and LOTC-3 retained the site. The biological characteristics of all the LOTC variants were similar to each other. Their plaque size and pock size were similar to those of LO, whereas they were rather akin to LC16m8 with regard to temperature sensitivity and neurovirulence. The present results strongly suggested that part of the HindIII D fragment was involved in determining biological characteristics affecting plaque size and pock size, but had little influence on temperature sensitivity and neurovirulence.

Animals↗

Human macrophage-activating factors for cytotoxicity. I. Establishment of a human T-cell hybridoma that produces macrophage-activating factors for cytotoxicity.

Human T cell hybridoma, H3-E9-6, that produces macrophage activating factors for cytotoxicity (MAF-C) was prepared by somatic fusion of phytohemagglutinin-activated peripheral blood lymphocytes with emetine/actinomycin D-treated cloned human acute lymphocytic leukemia cells (CEM 11). The activities of the following were assayed: (1) macrophage-activating factor for cytotoxicity of monocytes (MAF-C 1 day), (2) macrophage-activating factor for cytotoxicity of monocyte-derived macrophages (MAF-C 6 day), (3) macrophage-activating factor for cytotoxicity of murine macrophages (MAF-Cm), (4) macrophage-activating factor for glucose consumption (MAF-G), (5) macrophage-activating factor for O2- formation (MAF-O). The culture supernatant of H3-E9-6 showed MAF-C 1 day-MAF-C 6 day, MAF-Cm, and MAF-G activities. The MAF-Cm activity was considerably enhanced by the addition of murine recombinant interferon gamma (rIFN-gamma). The MAF-C 1 day activity in the H3-E9-6 sup was not decreased by heat treatment (56 C, 30 min), by pH 2 treatment or by the addition of monoclonal anti-human IFN-gamma antibody or polymyxin B. These data suggest that MAF-C in H3-E9-6 sup is distinct from human IFN-gamma or lipopolysaccharide (LPS).

Cytotoxicity, Immunologic↗

Human macrophage-activating factors for cytotoxicity. II. Synergism of two factors produced by a human T-cell hybridoma that induce the cytotoxicity of human monocytes.

Two different factors (MAF-C I and MAF-C II) were obtained by anion exchange chromatography of the culture supernatant of a human T-cell hybridoma, H3-E9-6, which produces macrophage-activating factors for cytotoxicity (MAF-C). These 2 factors induced the cytotoxicity of monocytes synergistically as a priming signal (MAF-C I) and a triggering signal (MAF-C II), respectively. On gel filtration on a column of Superose 12, MAF-C II was eluted mainly at the void volume, whereas MAF-C I was eluted in the fractions corresponding to approximate molecular weights of 30-300 K. On the other hand, gel filtration in the presence of sodium deoxycholate revealed that MAF-C II has an approximate molecular weight of 40,000, but MAF-C I was unstable under these conditions. When the activity for mouse macrophages (MAF-Cm activity) was tested, the MAF-C II fraction showed high MAF-Cm activity in the presence of murine recombinant interferon gamma (rIFN-gamma), but the MAF-C I fraction did not show MAF-Cm activity even in the presence of lipopolysaccharide (LPS). These results suggest that MAF-C I (priming lymphokine) has species specificity but MAF-C II (triggering lymphokine) does not.

Chromatography, Gel↗

SLE-like and sicca symptoms in late component (C9) complement deficiency.

Hereditary deficiencies in early and late complement components are well known to predispose to SLE-like syndromes or recurrent infection. Hitherto reported C9 deficient cases have usually been healthy subjects, however, and it is not considered that C9 deficiency is associated with any specific disease. We describe a completely C9 deficient patient with possible Sjögren's syndrome and discuss the relationship.

Autoimmune Diseases↗

Subunit heterogeneity of cationic human hepatic glutathione S-transferases.

We have purified the major reduced glutathione (GSH) S-transferases from 3 apparently normal human livers: two obtained at surgery and one at autopsy. Purification was by sequential gel filtration. GSH-affinity chromatography, and chromatofocusing. All three livers exhibited the same two major transferase peaks from chromatofocusing at pH 9.0 and 8.7 (designated C1 and C2, respectively) and several (2-4) minor peaks. Another major form (designated A1) from two livers eluted from chromatofocusing at pH 5.4, whereas the major form from the third liver (designated N1) eluted near neutral (pH 6.8). The transferase from erythrocytes eluted at pH 4.6. Isoelectric focusing revealed that the true pI of A1 was pH 7.1 indicating that C1, C2 and A1 are all cationic. In sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, C1, C2 and A1 exhibited the same single subunit (25,000) whereas N1 was different (26,000). The erythrocyte enzyme had a smaller subunit (23,500). Urea/SDS-polyacrylamide gel electrophoresis resolved the apparent single subunit of A1, C1 and C2 into two distinct subunits. C1 from all 3 livers was a homodimer of the faster migrating subunit (designated subunit I); C2 was a heterodimer (designated I-II); and A1 was a homodimer of the slower migrating subunit (designated subunit II). Hybridization experiments demonstrated that by mixing C1 and A1 we could produce C2 whereas dissociation and reassociation of the subunits of C2 generated C1 and A1 as well as C2. Rabbit antiserum to C1 recognized C1 and C2, but not A1. Thus, the cationic human hepatic transferases are dimers of two distinct subunits.

Amino Acids↗

Receptor-mediated O2- release by alveolar macrophages and peripheral blood monocytes from smokers and nonsmokers. Priming and triggering effects of monomeric IgG, concanavalin A, N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, and cytochalasin D.

Receptor-mediated superoxide (O2-) release by alveolar macrophages and peripheral blood monocytes from smokers and nonsmokers was studied in vitro. When the cells were incubated with monomeric IgG or monomeric Fc(IgG) fragment, no cell O2- release was observed. However, when cytochalasin D (Cyto D) was subsequently added to the cell suspension, we observed a markedly enhanced O2- release. Neither Cyto D alone nor the double stimulation of following Cyto D with monomeric IgG induced O2- release. Concanavalin A (Con A) also had a priming effect on O2 release in combination with Cyto D, as did monomeric IgG or monomeric Fc(IgG) fragment. On the other hand, heat-aggregated IgG, N-formyl-methionyl-leucyl-phenylalanine (FMLP), or phorbol myristate acetate (PMA) induced O2- release without the addition of Cyto D. Thus, we observed 2 different mechanisms in the receptor-mediated O2- release by alveolar macrophages and peripheral blood monocytes. Alveolar macrophages from smokers, which had a higher affinity and a larger number of monomeric IgG binding sites per cell than those from nonsmokers, were more reactive to the double stimulation of following monomeric IgG with Cyto D than to that of Con A and Cyto D, FMLP, or PMA, but for peripheral blood monocytes it was the reverse. We conclude that the binding of monomeric IgG to the Fc(IgG) receptor of alveolar macrophages or peripheral blood monocytes results in a priming effect on the cells for O2- release, and that the regulation of receptor-mediated O2- release by alveolar macrophages differs at least in part from that of peripheral blood monocytes.

Adult↗

Effects of afferent stimulation of the lingual nerve on gastrointestinal motility in the rat.

Effects of afferent stimulation of the lingual nerve (LNAS) on gastrointestinal motility and the reflex pathways which mediate the response to LNAS were investigated in rats. LNAS induced excitatory, inhibitory or biphasic responses in the stomach, duodenum and proximal colon. These responses continued after bilateral vagotomy, but were abolished after additional bilateral splanchnicotomy or transection of the spinal cord between Th4 and Th5. The inhibitory, excitatory and biphasic responses induced by LNAS were not affected by decerebration. Both after administration of atropine (0.2 mg/kg, i.v.) and guanethidine (3-5 mg/kg, i.v.), LNAS-induced excitatory and inhibitory responses were abolished in most cases, but the slight inhibitory response in the stomach and duodenum to LNAS remained in a few cases. These results suggest that the reflex centers which cause LNAS-induced excitatory and inhibitory responses are located in the dorsal nucleus of vagus and that the reflex pathways include the vagus and splanchnic nerves.

Afferent Pathways↗

Marked increase in serum alpha-fetoprotein level in cirrhosis: a case report.

A 56-yr-old Japanese man with chronic liver disease was admitted for evaluation of increased serum alpha-fetoprotein reaching levels as high as 7190 ng/ml. The presence of hepatocellular carcinoma was ruled out by computed tomography and hepatic angiography. Laparoscopy and liver biopsy sample showed active liver cirrhosis. alpha-Fetoprotein granules were positive in hepatocytes. The rise in serum alpha-fetoprotein level was transitory and returned to less than 100 ng/ml 4 wk later. It was suggested that regeneration after acute exacerbation of cirrhosis might have been closely related to the dramatic increase in alpha-fetoprotein production.

Chronic Disease↗