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Biomedical subjects

T Mimura

Publications and source records attributed to T Mimura.

At least 37 records · Page 2Linked to original sources

Autoantibodies to nucleolin in systemic lupus erythematosus and other diseases.

The 110-kDa intracellular phosphoprotein (110K) described previously by this laboratory as a common IgM autoantigen in SLE and certain other systemic autoimmune disorders and viral infections is identified as nucleolin in the present investigation. Using rabbit antiserum to rat nucleolin as a probe, IgM autoantibody-reactive 110K co-migrated with human lymphocyte nucleolin in one- and two-dimensional immunoblots. Rabbit anti-nucleolin also specifically depleted autoreactive 110K from detergent lysates of human cells. Because nucleolin shares amino acid sequence similarity and/or forms dynamic particles with other prominent autoantigens, the present observation raises the possibility that the nucleolin/anti-nucleolin system may be of special significance for the development of humoral autoreactivity to nuclear Ag.

Antibody Specificity

Autoantibodies to human stress proteins. A survey of various rheumatic and other inflammatory diseases.

Unselected sera from patients with various rheumatic, inflammatory bowel, and autoimmune skin diseases (n = 268) were examined against human cell lysate by immunoblotting procedures, to determine the prevalence of autoantibodies to stress proteins (heat-shock proteins) hsp60 (homolog of Escherichia coli groEL and mycobacterial 65K antigens), hsp73, and hsp90. Using standard, sensitive and specific assay conditions, IgG and IgM autoantibodies to these stress proteins were not demonstrable, or were detected infrequently, in sera from control subjects (n = 36) and from patients with rheumatoid arthritis, Sjögren's syndrome, ankylosing spondylitis, Reiter's syndrome, systemic lupus erythematosus, and systemic sclerosis. Autoantibodies to hsp60 were relatively more common (greater than or equal to 20% of sera) in patients with mixed connective tissue disease, polymyositis/dermatomyositis, psoriatic arthritis, inflammatory bowel disease, epidermolysis bullosa acquisita, and bullous pemphigoid. Anti-hsp73 autoantibodies were detected in 20% or more of the sera from patients with Lyme disease and ulcerative colitis. Taken together, these data extend the spectrum of autoimmune and inflammatory diseases in which humoral anti-stress protein autoreactivity develops. However, the paucity of humoral autoreactivity to stress proteins in patients with systemic lupus erythematosus and rheumatoid arthritis argues against a direct role of anti-stress protein autoantibodies in the pathogenesis of these disorders.

Autoantibodies

Solid adenosquamous carcinoma of the liver. A case report and review of the literature.

This is a report of a fatal case of a primary and solid adenosquamous carcinoma (ASC) of the liver in a 58-year-old Japanese woman. There was no association with biliary cysts. Histochemistry and immunohistochemistry support the contention that the neoplasm arose from squamous metaplasia of a mucus-secreting adenocarcinoma (MSA) of intrahepatic biliary duct epithelium.

Adenocarcinoma

Inhibitory effect of 2-(E-2-alkenoylamino)ethyl alkyl sulfides on gastric ulceration in rats. II. Structure and activity relationships of 2-(E-n or Z-n-Decenoylamino)ethyl alkyl sulfides.

The analogues of 2-(E-n or Z-n-decenoylamino)ethyl carbamoylmethyl sulfide, including the modifications of sulfide portion, double bond in decenoyl chain and alkyl sulfide moiety, were synthesized and their inhibitory effects on stress-induced ulceration in rats were compared. Replacing the sulfura atom by methylene group or oxygen atom reduced the effect of potency. Saturation of the double bond in the decenoyl chain tended to reduce the anti-ulcerogenic activity in rats. There was no relationship between the position of double bond in decenoyl chain and the pharmacological activity. On the other hand, compounds with E-configuration showed stronger anti-ulcer activity than the corresponding Z-type of compounds. Among 9 kinds of S substituted alkyl groups for carbamoylmethyl, 2-(E-2-decenoylamino)ethyl 2-cyclohexylethyl sulfide showed the most potent anti-ulcerogenic activity in rats and also showed the lowest acute toxicity in mice.

Animals

Effects of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide on various ulcer models in rats.

The effects of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide (compd. III-1a) on various experimental ulcers were investigated. The oral administration of compd. III-1a at doses ranging from 30 to 300 mg/kg inhibited the acute gastric ulcerations induced by ethanol, HCl.aspirin and indomethacin in rats. Compound III-1a significantly inhibited the water immersion stress-induced gastric ulcer at doses of 3 mg/kg, p.o. The anti-ulcer activity of plaunotol as a reference drug was equivalent on an ethanol-induced ulcer to that of compd. III-1a, but weaker on HCl.aspirin, indomethacin and stress-induced ulcers than that of compd. III-1a. On indomethacin-produced gastric antral ulcer, compd. III-1a showed the same significant inhibitory activity as spizofurone did at a dose of 100 mg/kg, p.o. Compound III-1a also inhibited hemorrhagic shock-, diethyldithiocarbamic acid (DDC)-and platelet activating factor (PAF)-induced ulcers dose-dependently. Plaunotol only showed significant inhibitory activity on PAF-induced ulcer in these three ucler models. The consecutive administration of compd. III-1a (100 mg/kg, p.o.) twice a day significantly accelerated the healing of an acetic acid-induced ulcer and that of plaunotol (200 mg/kg, p.o.) showed the same activity. Moreover, orally administered compd. III-1a at a dose of 100 mg/kg decreased the gastric acid secretion in pylorus-ligated rats. The results in the present study suggest that compd. III-1a has the dual action on ulcer formation.

Animals

Further studies on the anti-ulcerogenic effects of compound, 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide.

Tha anti-ulcerogenic mechanism of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide (compd. III-1a) was investigated in various gastric defensive factors. Compound III-1a maintained the high molecular glycoprotein (relative content of Fr. I hexose) and accelerated hexosamine synthesis which were reduced by water immersion stress. But plaunotol did not have these actions. The lipid peroxide level in the gastric mucosa from water immersion stressed rat was lowered by the administration of compd. III-1a. Compound III-1a maintained prostaglandin E2 (PGE2) and PGI2 contents which were reduced in the early phase of the stress and accelerated PGs synthesis in the late phase of the stress. Furthermore, compd. III-1a maintained phospholipase A2 (PLA2) activity which was reduced by the stress. The plaunotol treated group showed the same tendency as the compd. III-1a treated group on the lipid peroxide level, PGE2 and PGI2 contents, and PLA2 activity, but the potency of plaunotol was less than that of compd. III-1a. Compound III-1a accelerated gastric cell proliferation in pyloric glands of hydrocortisone treated rats. Tetragastrin accelerated significantly the cell proliferation in fundic glands. The sucralfate treated group showed the same tendency as the compd. III-1a treated group but the potency of sucralfate was less than that of compd. III-1a. The results in the present study suggest that compd. III-1a has a protective action on gastric mucosa.

Animals

Aryloxy acetic acid diuretics with uricosuric activity. I. Polycyclic aryloxy acetic acids.

In order to obtain lead compounds for uricosuric diuretics, various polycyclic aryloxy acetic acids [isoindole derivative (7), quinazoline derivative (15), benzopyran derivative (20), xanthone derivative (24), benzofuran derivative (30) and indene derivative (36)] were prepared. These compounds were evaluated for diuretic activity in rats, uricosuric activity in rats and antihypertensive activity in 11-deoxycorticosterone acetate (DOCA)/salt hypertensive rats. Among the compounds, 20 showed potent diuretic, uricosuric and moderate antihypertensive activities. Therefore, we selected 20 as a lead compound for development of new uricosuric diuretics.

Acetates

Isolation of a new antitumor substance from Bacillus stearothermophilus.

A new antitumor substance, BS-1, was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563 by ethylacetate extraction and HPLC. BS-1 inhibited the proliferation of mouse macrophage-like cells, P388-D1 (IC50: 4 micrograms/ml) and mouse mastocytoma, P-815 (IC50: 0.6 microgram/ml), but not that of Balb/c 3T3.

Animals

Constitutive expression of a groEL-related protein on the surface of human gamma/delta cells.

Rabbit antibodies to hsp58 (P1), the human homologue of the Escherichia coli stress protein groEL, react specifically in indirect immunofluorescence and complement-dependent microcytoxicity experiments with a cell surface antigen expressed constitutively by T cell lines bearing gamma/delta receptors. This anti-hsp58-reactive antigen is not demonstrable on T cells that express alpha/beta receptors or on various cells that lack T cell receptors. Certain evidence was obtained to suggest that the target antigen on the surface of gamma/delta T cells is a approximately 77-kD protein distinct from intracellular hsp58 and known members of the hsp70 stress protein family. While the exact nature and significance of this anti-hsp58-reactive protein remain to be determined, these data may help to clarify the roles of groEL-related stress proteins and gamma/delta cells that recognize groEL homologous in immunologic defense against infection and in autoimmune disease.

Antibodies

Autoantibodies specific for different isoforms of CD45 in systemic lupus erythematosus.

Nearly one-third of IgM antilymphocyte autoantibody-positive sera from patients with systemic lupus erythematosus (SLE) contain IgM antibodies to one or more 180-220-kD molecules (p180, p190, p205, and p220) in blots of glycoproteins purified from T cells by wheat germ agglutinin affinity chromatography. Identity of these IgM targets with multiple isoforms of CD45 was established by their specific depletion from T cell glycoproteins by immunoprecipitation with T191, a monoclonal antibody (mAb) that reacts with an epitope common to all CD45 isoforms. Although the anti-CD45 autoantibodies recognize higher molecular weight isoforms primarily, antigenic specificity in this system is quite heterogeneous and includes multiple distinct CD45 isoforms on different types of T cells that are, at least in part, different from those reactive with mAbs 2H4 and UCHL-1. Because CD45 is a major membrane protein tyrosine phosphatase that plays a critical role in antigen-induced T cell activation, the present data may be relevant to some of the antilymphocyte antibody-mediated immunologic abnormalities that characterize SLE and related autoimmune diseases.

Antigens, CD

Reactivity of autoantibodies and DNA/anti-DNA complexes with a novel 110-kilodalton phosphoprotein in systemic lupus erythematosus and other diseases.

Utilizing nonionic detergent lysates of human lymphoid and non-lymphoid cells as substrate, IgM and/or IgG antibodies to a 110-kDa/isoelectric point 5.4 phosphoprotein (110K) was demonstrated in serum from patients with SLE or certain other systemic autoimmune disorders by immunoblotting and immunoprecipitation. Ig of this specificity was not demonstrable in serum from normal individuals, but, in a limited survey, was detected in serum from patients with acute hepatitis A or infectious mononucleosis. 110K shares a number of properties with nucleolin, i.e., identical Mr and isoelectric point, localization in both the nucleus and the cytosol, increased expression in rapidly dividing cells, and shown to be distinct from already defined autoantigens of similar size, i.e., topoisomerase I, PM-Scl, and RNA polymerase I. Because 110K could bind denatured DNA, as demonstrated by its specific absorption by DNA-cellulose and by its reactivity with monoclonal anti-ssDNA antibody in the presence of denatured DNA, special efforts were made to distinguish reactivity of pre-formed DNA/anti-DNA complexes in SLE serum from that due to specific anti-110K autoantibodies. Although binding to 110K could be mediated by DNA and anti-DNA in some SLE sera, the accumulated evidence supports the existence of a major new autoantibody system in SLE, other autoimmune diseases, and certain virus infections.

Antibodies, Antinuclear

Glycoprotein specificity of cold-reactive IgM antilymphocyte autoantibodies in systemic lupus erythematosus.

Sera from patients with systemic lupus erythematosus frequently contain IgM antibodies to glycoproteins of Mr 46,000 and approximately 200,000 isolated from nonionic detergent lysates of mature T cells by affinity chromatography with solid-phase wheat germ agglutinin. Autoantibodies of this specificity correlate strongly with the presence of IgM anti-T cell autoantibodies, as determined by independent indirect immunofluorescence and complement-dependent microcytotoxicity assays, and are specifically absorbed by incubation of patient serum with viable T cells. Collectively, the data suggest that gp46 and, to a lesser extent, gp approximately 200 represent major targets of IgM antilymphocyte autoantibodies in systemic lupus erythematosus.

Antibody Specificity

A human sperm antigen possibly involved in binding and/or fusion with zona-free hamster eggs.

A monoclonal antibody to human sperm (MH61) was established. The antibody did not attach to ejaculated sperm but to a head region of some sperm that was incubated in medium for 4 to 12 hours. A23187 treatment significantly increased the number of sperm that were reactive to the antibody. When sperm that bound to the zona-free hamster egg were subjected to the indirect immunofluorescence staining, all the sperm reacted to MH61 with their entire head region. The addition of the antibody to the medium before sperm addition reduced the fusion rate of human sperm to zona-free hamster egg.

Acrosome

Production of angiotensin-converting enzyme inhibitors from baker's yeast glyceraldehyde-3-phosphate dehydrogenase.

Angiotensin-converting enzyme (ACE) inhibitors were excised from the molecule of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of baker's yeast by heating at 120 degrees C in 1 M AcOH-20 mM HCl. Three inhibitors were then purified by gel-permeation and reverse-phase chromatographies. One of the yeast ACE inhibitors, YG-3, was GAPDH peptide 79-89 (Pro-Ala-Asn-Leu-Pro-Trp-Gly-Ser-Ser-Asn-Val, IC50:18 microM), and contained the sequence homologous to vertebrate ACE inhibitors (GAPDH peptides 79-86 or 81-88). Other inhibitors, YG-1 (Gly-His-Lys-Ile-Ala-Thr-Phe-Gln-Glu-Arg, IC50: 0.4 microM) and YG-2 (Gly-Lys-Lys-Ile-Ala-Thr-Tyr-Gln-Glu-Arg, IC50: 2 microM), corresponded to amino acid residues 68-77 in two different forms of yeast GAPDH, respectively. Their sequences were quite different from those of the venom peptide family. YG-1 was the most potent ACE inhibitor among yeast and vertebrate GAPDH peptides excised by acid-limited proteolysis. Thus, yeast GAPDH seems to be an excellent source of naturally occurring ACE inhibitors.

Amino Acid Sequence

Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase as a source of angiotensin-converting enzyme inhibitors.

The more potent inhibitory activity against angiotensin-converting enzyme (ACE) was excised from a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of Bacillus stearothermophilus by heating at 120 degrees C in 1 M AcOH-20 mM HCl, as compared with GAPDH preparations of yeast and pig. Sufficient excision of B. stearothermophilus ACE inhibitors required a longer proteolysis time of 60 min. Two inhibitors were then purified by gel-permeation and reverse-phase chromatographies. One of the B. stearothermophilus ACE inhibitors BG-1, was the GAPDH peptide 68-77 (Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg, IC50: 32 microM). Another inhibitor, BG-2 (Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr, IC50: 6 microM), correspond to GAPDH peptide 304-313. These sequences were quite different from those of vertebrate GAPDH peptides and the venom peptide family with ACE inhibitory activity. BG-2 was found to be a non-competitive type inhibitor, differing from many natural peptide inhibitors. Thus, B. stearothermophilus GAPDH seemed to be a good source of new type ACE inhibitors, in addition to the advantages due to its thermophilic property.

Amino Acid Sequence