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Biomedical subjects

S Hirose

Publications and source records attributed to S Hirose.

At least 325 records · Page 18Linked to original sources
PubMed1994

[Corticosteroid therapy in collagen disease].

Corticosteroids are used commonly in the management of collagen disease and related condition. The degree of disease activity and clonicity should be clearly evaluated as therapeutic strategies of corticosteroids. High dose corticosteroids including pulse-therapy is useful for SLE with CNS-lupus, lupus nephritis and hemolytic anemia. Dermatomyositis also require high dose corticosteroids and it should keep for long time. PN is effective combination therapy of corticosteroids and cyclophosphamide. PMR and Temporal Arthritis well response dramatically to corticosteroids. RA should not be administrate over 7.5 m/day of CS. Intra-auticular therapy and alternate-day therapy are recommended in in-active RA.

Collagen Diseases↗
PubMed1993

A candidate mammalian glycoinositol phospholipid precursor containing three phosphoethanolamines.

The glycoinositol phospholipid (GPI) anchors of mammalian proteins contain linear ethanolamine (EthN)-P-6ManManManGlcN glycan sequences that bear additional EthN-P substituents and in some cases include a fourth Man and a GalNAc or sialic acid-GalGalNAc. Precursors of these anchoring structures are preassembled in the endoplasmic reticulum by sequential glycosylation of inositol phospholipid. In previous studies (Hirose, S., Prince, G. M, Sevlever, D., Ravi, L., Rosenberry, T. L., Ueda, E., and Medof, M. E. (1992) J. Biol. Chem. 267, 16968-16974), a series of putative intermediates of this assembly process were isolated from human HeLa cells and murine lymphomas, and several of the more polar products were found to contain a second EthN-P attached to the Man residue (Man 1) proximal to GlcN. In this study, the most polar HeLa cell GPI species was purified by normal phase HeLa cell GPI species was purified by normal phase Iatrobead high performance liquid chromatography, and its glycan was characterized. Dionex anion exchange chromatographic analyses of fragments produced by nitrous acid deamination, hydrofluoric acid dephosphorylation, and trifluoroacetic acid hydrolysis in conjunction with biosynthetic labeling studies indicated a structure containing a third EthN-P substituent linked to the 6-position of Man 2. The polar GPI product exhibited a ManManManGlcN core lacking additional Man or GalNAc. The implications of the identification of this triply phosphoethanolamine-substituted species to mammalian GPI anchor biosynthesis are discussed.

Carbohydrate Sequence↗
PubMed1993

Underwinding of DNA on binding of yeast TFIID to the TATA element.

The TATA box-binding factor TFIID is an essential component for the initiation of transcription by eukaryotic RNA polymerase II. We investigated the effect of DNA supercoiling on TFIID: promoter interactions using recombinant yeast (ry) TFIID. DNase I footprinting analysis showed that ryTFIID has a higher affinity for the adenovirus major late promoter in the negatively supercoiled state than that in the relaxed state. On the contrary, its affinity for the Drosophila hsp70 promoter is constant irrespective of DNA topology. Binding of ryTFIID to these promoters induced underwinding of duplex DNA. The functional TATA box and active ryTFIID are essential for the underwinding. The step was facilitated by negative supercoiling of DNA on the adenovirus major late promoter but not on the Drosophila hsp70 promoter.

Animals↗
PubMed1993

A variant form of the type C atrial natriuretic peptide receptor generated by alternative RNA splicing.

A novel form of type C atrial natriuretic peptide receptor (ANP-C) was identified, characterized, and shown to be a product of alternative RNA splicing. Sequencing of several clones of ANP-C cDNA isolated from a bovine lung cDNA library revealed the presence of a new clone encoding a 536-amino acid ANP-C. The nucleotide sequence of this novel clone is very similar to that of the previously cloned ANP-C which consists of 537 amino acids. The sole difference between the two clones is the presence or absence of a very short segment of only 3 base pairs (bp), by which the sequence Ser472-Gly473 of the longer form is changed to Cys472 in the variant form; the other regions are identical. Alignment of the cDNA sequences with that of the ANP-C gene indicated that the two forms of ANP-C receptor arise from a single gene by alternative splicing using one donor and two closely located acceptor sites. Biochemical and pharmacological characterization using a mammalian cDNA expression system indicated that the two variants are similar in their subunit structures, in ligand-binding properties, and even in internalization kinetics. Polymerase chain reaction amplification of the transcripts demonstrated that 1) although the novel form is a minor species, it is present in various tissues such as the lung, kidney, adrenal, and vascular smooth muscle and endothelial cells and 2) the ratio of the novel variant form to the original longer form remains almost constant in these tissues. The alternative splicing reported here contributes to the diversity of ANP receptors; however, its physiological significance remains to be clarified.

Affinity Labels↗
PubMed1993

Deficient biosynthesis of N-acetylglucosaminyl-phosphatidylinositol, the first intermediate of glycosyl phosphatidylinositol anchor biosynthesis, in cell lines established from patients with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic disorder caused by a deficiency of biosynthesis of the glycosyl phosphatidylinositol (GPI) anchor, but the biochemical defect is not completely understood. In the present study, we have analyzed affected cell lines established recently from two Japanese patients with PNH. Two lines of evidence indicate that these cells do not synthesize N-acetylglucosaminyl-phosphatidylinositol, the first intermediate in the GPI anchor biosynthesis. First, somatic cell hybridization analysis using Thy-1-deficient murine thymoma cell lines with known biochemical defects as fusion partners showed that the PNH cell lines belong to complementation class A, which is known not to synthesize N-acetylglucosaminyl-phosphatidylinositol. Second, analysis of in vitro glycolipid biosynthesis demonstrated that cell lysates of these PNH cell lines in fact did not support biosynthesis of N-acetylglucosaminyl-phosphatidylinositol. Thus, we have characterized for the first time the exact biochemical defect leading to PNH.

Cells, Cultured↗
PubMed1993

Somatic diversification and affinity maturation of IgM and IgG anti-DNA antibodies in murine lupus.

Molecular events occurring during the process of generation of pathogenic immunoglobulin (Ig)G anti-DNA antibodies in systemic lupus erythematosus (SLE) were studied using a newly established method. We analyzed the Ig variable (V) region gene sequence and DNA-binding activity of IgM and IgG anti-DNA monoclonal antibodies (mAb) from individual SLE-prone (NZB x NZW) F1 mice. The first event appeared to be clonal selection and expansion of IgM anti-DNA clones, in which several clones had intraclonal V gene mutations. Although the number of mutations was small, the mutated IgM clones were associated with an increase in DNA-binding activity. The somatic mutations located in complementarity-determining regions (CDR) and in framework regions (FR) of V genes were apparently related to changes in DNA-binding activity. IgG anti-DNA clones that progressively increased in number with aging had numerous somatic mutations in the V region genes and there was a pair of clones which showed an intraclonal accumulation of mutations, in association with increase in the DNA-binding activity. All these findings show that somatic mutations associated with affinity maturation of the V region begin immediately before isotype-switching from IgM to IgG of the clones that have been selected and expanded, in an antigen-driven manner and/or by other forces. We propose that further accumulations of intraclonal somatic hypermutation, in association with selection and expansion of high affinity IgG clones, may lead to formation of highly pathogenic anti-DNA antibodies.

Age Factors↗
PubMed1993

Increased IgE level as a marker of host-versus-graft disease: inhibition of this HVGD with a monoclonal antibody to IL-4.

BALB/c mice injected at birth with (BALB/c x C57BL/6)F1 hybrid spleen cells developed host versus graft disease (HVGD) with immunological features, such as various autoantibodies, immune complex nephritis, hepatosplenomegaly, and malignant lymphomas. In addition we found that the increased IgE levels correlated strongly with the histological grades or stages of the liver disease. In the sera of mice with HVGD and liver alterations, anti-smooth muscle antibodies (ASMA) and anti-nuclear antibodies (ANA) were detected. The subclass of ASMA was IgG1, whereas the subclasses of ANA were IgG1, IgG2a, and IgG2b. When the recipient BALB/c mice were injected at birth and at Day 3 in addition also with monoclonal anti-IL-4 antibody 11B11, the increase of IgE and IgG1 was markedly reduced and the liver disease was drastically prevented. These observations suggest that IL-4 plays an important role in the initiation of the immunoregulatory function or pathogenesis of the allogeneic effects and that the monoclonal anti-IL-4 antibody 11B11 prevents the immunodysfunctions and the autoimmune hepatopathy in mice with HVGD. The increased IgE level in the serum is a good marker of HVGD.

Animals↗
PubMed1993

DNA sequence requirement of a TATA element-binding protein from Arabidopsis for transcription in vitro.

We have analyzed the DNA sequence requirements for the functioning of TATA elements by examining the transcriptional activities associated with 24 promoters, including representatives of each of the 21 point mutations in the consensus sequence from plants, TATATATA, in a HeLa in vitro system and in a chimeric in vitro system in which human TATA-binding protein (hTBP) was replaced by purified TBP of Arabidopsis (aTBP-1). Although the relative transcriptional activities varied among these promoters, both systems gave virtually identical results. Among the mutant TATA elements, those with the sequences TAGAGATA and GAGAGAGA had undetectable activity. The rest had activities that ranged from 7% to 130% of the activity associated with the consensus element. These results suggest the functional conservation of TBP between plants and animals.

Arabidopsis↗
PubMed1993

Soluble CD4, CD8 in patients with polymyositis/dermatomyositis.

The concentrations of soluble CD4 (sCD4) and soluble CD8 (sCD8) were determined in 64 patients with polymyositis/dermatomyositis (PM/MD). The patients with PM/DM had significantly higher concentrations of sCD8, though the concentrations of sCD4 did not significantly increase. Patients with high concentrations of sCD8 tended to have too high concentrations of soluble interleukin-2 receptor (sIL-2R). The patients with high levels of myogenic enzymes tended to have high concentrations of sCD8. The results of a serial study indicated that the concentrations of sCD8 decreased simultaneously with the decrease of the myogenic enzymes. These results may suggest that the activation of CD8+ cells are related to muscular involvement.

Adult↗
PubMed1993

Soluble CD4 and CD8 molecules in patients with systemic sclerosis.

The concentrations of sCD4 and sCD8 in 69 patients with systemic sclerosis (SSc) were examined by using a sandwich enzyme-linked immunosorbent assay. The patients with SSc had significantly higher concentrations of sCD8 (mean 249.2 U/ml (SD 155.1), median 224 U/ml) than the normal subjects (mean 149.3 U/ml (SD 42.1), median 148 U/ml). The concentration of sCD4 in patients with SSc were significantly lower (mean 6.2 U/ml (SD 3.8), median 5.0 U/ml) than in the normal subjects (mean 10.9 U/ml (SD 4.1), median 10.3 U/ml). The concentration of sCD8 in patients with diffuse sclerosis tended to be higher than in those with sclerodactyly.

Adult↗
PubMed1993

Endothelium localization of ETB receptor revealed by immunohistochemistry.

The ETB receptor has been found to be predominantly expressed in the vascular endothelium of various bovine tissues by immunostaining with a highly specific antiserum that does not cross-react with ETA. The tissues examined include the lung, trachea, kidney, adrenal gland, pituitary gland, and cerebellum. The wide-spread localization of ETB in the endothelial lining suggests that there is an ETB-mediated autocrine system of endothelin, which plays an important role in regulation of the functions of endothelial cells.

Animals↗
PubMed1993

H-2z homozygous New Zealand mice as a model for B-cell chronic lymphocytic leukemia: elevated bcl-2 expression in CD5 B cells at premalignant and malignant stages.

In New Zealand mice, the major histocompatibility complex (MHC) controls the development of both autoimmune disease and B cell chronic lymphocytic leukemia (B-CLL). While H-2d/H-2z heterozygosity acts as one major predisposing genetic element for autoimmune disease, H-2z/H-2z homozygosity acts as an element for B-CLL. In the H-2z/H-2z homozygotes, there was an age-dependent increase in frequencies of CD5 B cells in the blood and spleen, and such CD5 B cells showed oligoclonal to monoclonal expansion, giving rise to B-CLL. B-CLL cells from these mice had surface phenotypes typical of CD5 B lineage cells, and expressed high levels of proto-oncogene bcl-2. Elevated bcl-2 expression was also observed in premalignant B cells in the aged mice, thereby suggesting that apoptosis-resistant, long-surviving CD5 B cells with a self-renewal capacity form the basis of malignant transformation. This model not only provides clues for analyzing multiple steps of genetic alterations involved in the generation of B-CLL, but also sheds light on the correlation between B-CLL and autoimmune disease.

Animals↗
PubMed1993

Protein-losing enteropathy due to secondary amyloidosis of the gastrointestinal tract.

A case of a 71 year old woman who experienced weight loss, diarrhea and edema due to protein-losing enteropathy caused by amyloidosis secondary to rheumatoid arthritis is described. Amyloid deposits were found in the systemic organs, specifically in the bowel. The arterioles were massively involved within the laminae propriae and many were narrowed considerably due to amyloid deposits. Ulcerative lesions, which were accompanied with the ruptured arterioles, were also found. Lymphangiectasia was present in the submucosa, subserosa and mesenterium. The mesenteric lymphatic vessels were deposited markedly with amyloid. The principal cause of the protein loss might be related to the increased capillary permeability to plasma proteins and the exudation through an inflamed mucosa. Functional disruption of the lymphatic flow in the bowel and mesenterium might also participate in the mechanisms of the protein loss. Evidence in this study supports the theory that lymphatic disorders in some patients with gastrointestinal amyloidosis are one of the important factors in the pathogenesis of protein-losing enteropathy.

Aged↗