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Biomedical subjects

T Mimori

Publications and source records attributed to T Mimori.

At least 127 records · Page 7Linked to original sources

Autoantibodies against Forssman glycolipids in Graves' disease and Hashimoto's thyroiditis.

Sera from patients with Graves' disease and Hashimoto's thyroiditis have been shown to react with the Forssman glycolipid antigen (Gb5) using the techniques of high performance thin-layer chromatography (HPTLC) immunostaining and ELISA. Human monoclonal antibodies (MoAbs) have been prepared by fusion of human myeloma with peripheral lymphocytes from patients with Graves' disease. A MoAb, TRMo-4, reacted strongly and specifically with Gb5. These results suggest that anti-Forssman antibody may be involved in the pathogenesis of these autoimmune diseases. The detection of anti-Forssman glycolipid antibody may provide a useful means for clinical diagnosis and therapy.

Antibodies, Monoclonal↗

Andean leishmaniasis in Ecuador caused by infection with Leishmania mexicana and L. major-like parasites.

Between 1986 and 1988, epidemiologic studies were carried out in a small rural community in an Andean region of Ecuador, where cutaneous leishmaniasis is highly endemic. A total of 25 human cases, positive for Leishmania parasites by culture and/or smear, were examined. Fourteen of the cases were in infants less than one year of age, suggesting intradomiciliary transmission of the disease. Clinically, many of these cases were similar to descriptions of "uta," a form of cutaneous leishmaniasis which occurs in Andean regions of Peru and is reported caused by L. peruviana. Of the 11 positive cultures obtained from human cases in the present study, eight were identified by molecular characterization as L. mexicana and three were identified as L. major-like. Two additional isolates of L. mexicana were also made from an infected dog and from a sand fly, Lutzomyia ayacuchensis, living in the region, thus implicating the latter species as possible reservoir and vector, respectively, of L. mexicana in this highland community. The significance and validity of recent isolates of L. major-like parasites from the New World are also discussed.

Animals↗

A novel autoantibody reactive with a 48 kDa tRNA associated protein in patients with scleroderma.

We identify 4 patients with progressive systemic sclerosis (PSS) possessing a previously undescribed serum anti-tRNA Ab (anti-Wa antibody). These sera yielded identical precipitin lines under double immunodiffusion using calf thymus extract and supernatant of pig spleen homogenate as antigen sources. Furthermore, all 4 sera were found to react with a 48 kDa protein using immunoblotting. This protein was subsequently found to be associated with tRNA when immunoprecipitation was conducted. In a survey of autoimmune patients' sera, anti-Wa Ab was observed in 3% (4 of 130) of patients with PSS, but not in other systemic rheumatic diseases. None of the 4 patients with PSS with anti-Wa Ab had myositis except that one patient complained of mild myalgia.

Aged↗

Isolation and characterization of cDNA encoding the 80-kDa subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome.

Anti-Ku (p70/p80) autoantibodies in patients with scleroderma-polymyositis overlap syndrome recognize a 70-kDa/80-kDa protein heterodimer which binds to terminal regions of double-stranded DNA. In the present study, we isolated full-length cDNAs that encode the 80-kDa Ku subunit. Initial screening of a human spleen cDNA library with anti-Ku antibodies yielded a cDNA of 1.0 kilobase (kb) (termed K71) encoding a portion of the 80-kDa Ku polypeptide (identification based on immunological criteria). In RNA blots, this cDNA hybridized with two mRNAs of 3.4 and 2.6 kb. In rescreening of a cDNA library constructed from simian virus 40-transformed human fibroblast mRNA with the K71 cDNA as a hybridization probe, three positive clones were isolated, and that bearing the longest insert (termed Ku80-6) was selected for further characterization. In vitro transcription and translation experiments produced an immunoprecipitable polypeptide which comigrated with the 80-kDa Ku subunit. The Ku80-6 cDNA proved to be 3304 nucleotides in length, with an additional poly(A) tail, closely approximating the size of the larger mRNA. It contains a single long open reading frame encoding 732 amino acids (Mr = 82,713). The putative polypeptide has a high content of acidic amino acids and a region with periodic repeat of leucine in every seventh position which may form the "leucine zipper" structure. In genomic DNA blots, probes derived from the opposite ends of cDNA Ku80-6 hybridized with several nonoverlapping restriction fragments from human leukocyte DNA, indicating that the gene encoding the 80-kDa Ku polypeptide is divided into several exons by intervening sequences.

Amino Acid Sequence↗

The acquirement of growth ability for third-stage larvae of Strongyloides ratti during the head-passage in the rat.

The role of larval passage through the head in the course of the migration of Strongyloides ratti in rats was investigated. Third-stage larvae (L3) recovered from various portions of donor rats were re-injected into the skin, cranial cavity and small intestine of recipient rats to check their ability for further growth. Cultured L3 (L3c) and the L3 recovered from the skin of donor rats (L3s) did not survive in the small intestine after intestinal inoculation. However, intestinal inoculation of L3 recovered from the head of donor rats (L3h) revealed growth to the adult stage. Cultured L3 injected into the cranial cavity of rats also became adult worms in the small intestine. L3 incubated in the cranial cavity for more than 24 h could grow in the small intestine of the recipient rats. These experiments suggest that S. ratti L3 acquire their ability to mature in the small intestine during their migration through the head of rats.

Animals↗

The effect of fatty acids on the developmental direction of Strongyloides ratti first-stage larvae.

The effect of fatty acids was studied on the developmental direction of Strongyloides ratti first-stage larvae (L1). The proportion of third-stage infective larvae increased markedly when L1 were cultured in faeces with added fatty acids such as palmitic (C16), stearic (C18), oleic (C18:1) and linoleic (C18:2) acids. Unsaturated fatty acids were more effective than saturated ones. Moreover, the proportion of infective larvae increased with quantity of linoleic acid but the triacylglycerols of any fatty acid had no effect. These results suggest that these free fatty acids cause physiological changes that determine the developmental course of L1 of S. ratti in nature.

Animals↗

Molecular cloning of cDNA encoding Sm autoantigen: derivation of a cDNA for a B polypeptide of the U series of small nuclear ribonucleoprotein particles.

The Sm snRNPs play a central role in the processing of pre-mRNA. Anti-Sm antibodies, the diagnostic hallmark of systemic lupus erythematosus, target the B'/B and D polypeptides of these snRNPs. We have used patient autoantibodies to clone a cDNA from a human fibroblast cDNA library that encodes the full length of a polypeptide identical with, or closely related to, polypeptide B. This cDNA is comprised of 1139 bases and contains an open reading frame of 855 nucleotides that is capable of encoding 285 amino acids. The first 223 amino acids at the NH2 terminus exhibit nearly complete homology with polypeptide N, a newly recognized brain- and heart-specific component of Sm snRNPs. The derived amino acid sequence for B differs from that of the N polypeptide primarily by a 50-amino acid insert 12 residues upstream from the homologous COOH termini of these polypeptides. The structural differences in these cDNAs for B and N may regulate tissue-specific alternative splicing mechanisms for mRNA. In addition, these clones make it possible to map in fine detail the most characteristic autoimmune responses of systemic lupus erythematosus.

Amino Acid Sequence↗

Identification, using isoenzyme electrophoresis and monoclonal antibodies, of Leishmania isolated from humans and wild animals of Ecuador.

Six strains of Leishmania isolated from wild mammals and humans on the Pacific Coast of Ecuador were identified by isoenzyme electrophoresis and by their reactivity patterns to a cross-panel of specific monoclonal antibodies using a radioimmune binding assay. Single isolates from Sciurus vulgaris, Potos flavus, and Tamandua tetradactyla were identified as Leishmania amazonensis. Three other strains, isolated from cutaneous lesions of humans, were identified as Leishmania panamensis.

Animals↗

[Frequency of anti-centromere antibodies in the anti-mitochondrial antibody positive sera].

Autoantibodies give us useful informations for the understanding of the co-existence of multiple autoimmune diseases in an individual patient. This study was undertaken to clarify the frequency of anti-centromere antibodies in the sera which were positive for anti-mitochondrial antibodies. Serum samples with anti-mitochondrial antibodies were examined on the frozen rat liver section and HEp-2 cells by indirect immunofluorescence. 57 out of 239 anti-mitochondrial antibody positive sera were found to contain specific autoantibodies reactive with centromeric antigens of the HEp-2 chromosomal spreads. The co-existence of anticentromere antibodies with anti-mitochondrial antibodies were significantly more frequent than with other defined autoantibodies. Clinical observation which shows frequent association of CREST syndrome and primary biliary cirrhosis appear to be explained by the frequent occurrence of anti-centromere antibodies and anti-mitochondrial antibodies.

Autoantibodies↗

The U2 small nuclear ribonucleoprotein particle as an autoantigen. Analysis with sera from patients with overlap syndromes.

We identified eight patients whose sera contained autoantibodies to the U2 small nuclear ribonucleoprotein (snRNP), an RNA protein particle involved in the splicing of newly transcribed messenger RNA. Each of these patients had an overlap syndrome that included features of either systemic lupus erythematosus (SLE), scleroderma, and/or polymyositis. We then used these sera to characterize the autoantigenic polypeptides of the U1 and U2 snRNP particles. In immunoblots, all sera contained antibodies to the B" polypeptide of the U2 snRNP. A subset of these sera that more effectively immunoprecipitated the native U2 particle contained an additional antibody system that recognized the A' polypeptide of this snRNP. Antibodies eluted from the B" protein bound the A polypeptide of the U1 snRNP and vice versa. Moreover, antibodies to the B" polypeptide were accompanied by antibodies to the 68K and C polypeptides of the U1 snRNP. Finally, the A' and B" polypeptides remained physically associated after the U2 particle was cleaved with RNase. Thus these sera contain multiple autoantibody systems that, at one level, target two physically associated antigenic polypeptides of the U2 particle and, at another, target two snRNP particles which are associated during the splicing of premessenger RNA. These linked autoantibody sets provide further evidence that intact macromolecular structures are targeted by the immune response in SLE and related diseases.

Autoantibodies↗

Characterization of human autoantibodies that selectively precipitate the 7SL RNA component of the signal recognition particle.

The signal recognition particle (SRP), which consists of the 7SL RNA molecule associated with six polypeptides ranging between 9,000 and 72,000 m.w., mediates the translocation of newly synthesized proteins across the endoplasmic reticulum. We have characterized autoantibodies that are directed against this particle from two patients with rheumatic diseases. These sera immunoprecipitated the 7SL RNA from whole extracts of HeLa cells radiolabeled with 32P, but no RNA from deproteinized cell extracts. From 35S-methionine-labeled cell extracts, they immunoprecipitated a single polypeptide of 54,000 m.w. that is consistent with a known SRP component. Sucrose density gradient studies confirmed that this protein co-migrated with the 7SL RNA, indicating the likelihood that it is physically associated with this RNA. Thus, the 54,000 m.w. SRP protein, which is essential for the SRP functions of elongation arrest and translocation, appears to be a preferential target for human autoimmune responses. Human autoantibodies that recognize the SRP should be useful adjuncts to animal antisera for studies of the structure and function of this particle.

Arthritis↗

Hypertrophic osteoarthropathy, cutaneous vasculitis, and mixed-type cryoglobulinemia in a patient with nasopharyngeal carcinoma.

We describe a 27-year-old woman with a primary nasopharyngeal carcinoma who developed hypertrophic osteoarthropathy and cutaneous vasculitis. Her serum contained antibodies to Epstein-Barr virus and U1 RNP antigens. Cryoproteins isolated from her serum contained antibodies to U1 RNP and a protein with a molecular weight of 32 kd which reacted specifically with antibodies to U1 RNP. HLA typing revealed HLA-B7 and DR1; these have been reported to be increased in Japanese patients with rheumatic diseases who have autoantibodies to U1 RNP. These findings indicate that some features of the paraneoplastic syndrome in this patient might have been caused by immune complexes, part of which were formed by specific autoantibodies produced under genetically controlled conditions of immune responsiveness.

Adult↗

Strongyloides ratti: formation of protection in rats by excretory/secretory products of adult worms.

Formation of a marked protective immunity against the challenge infection was found in the rats immunized with excretory/secretory (ES) products of Strongyloides ratti adult worms. Immunization by intraduodenal injection of ES products reduced both the fecal egg counts and the adult worm burden by subcutaneous inoculation of infective larvae and by an intraduodenal implantation. The duration of parasitism in the immunized rats, however, was not shortened compared with that of control rats. The normal migration of subcutaneously challenged larvae was not affected by ES product immunization. Intestinal mastocytosis occurred according to the appearance of adult worms in the small intestine of the immunized rats earlier than it did in controls. This result suggests that mastocytosis is involved in the induction of protection by ES products of S. ratti adult worms.

Animals↗

Association of electrocardiographic abnormalities with seropositivity to Trypanosoma cruzi in Ecuador.

In highland Ecuador (province of El Oro), electrocardiograms (ECGs) were taken and analysed from 340 subjects, of whom 154 were seropositive to Trypanosoma cruzi by indirect haemagglutination test. Abnormal ECGs were present in 40.3% of seropositive individuals and 8.1% of seronegatives, and were slightly more common in seropositive males than in seropositive females. In seropositive individuals, the prevalence of abnormal ECG progressively increased with age and reached its peak level of 64.0% in the age group over 60 years, implying that Chagas disease in Ecuador produces little mortality among seropositive individuals. The most common ECG alterations were ventricular conduction defects: 26 of 117 seropositive individuals in the age group over 40 years had complete right bundle branch block. The frequency of atrioventricular block and arrhythmias was also associated with seropositivity to T. cruzi. A further ECG examination in lowland (province of Guayas) showed that the prevalence of abnormal ECGs there was significantly lower than that in highlands. These results suggest possible differences between T. cruzi strains in the two geographical areas of Ecuador.

Adolescent↗