Search PubMed⌕ Search

Biomedical subjects

S Hirose

Publications and source records attributed to S Hirose.

At least 217 records · Page 12Linked to original sources
PubMed1997

[Breakdown of B cell-tolerance and its genetic control].

We examined Fas expression level and apoptosis-sensitivity of autoantibody-producing B cells in systemic lupus erythematosus-prone (NZB x NZW)F1 mice. In young mice, B cells expressed little Fas. However, stimulation with anti-CD40 mAb up-regulated Fas expression, in which B cells were divided into two groups, one Fas(high), apoptosis-sensitive and the other Fas(low), apoptosis-resistant. In aged mice with overt SLE, a considerable proportion of B cells spontaneously expressed low level of Fas with apoptosis-resistant phenotype. Anti-DNA antibodies were virtually produced by apoptosis-resistant Fas(low) B cells in both young and aged mice.

Animals↗
PubMed1997

Genetic factors predisposing to B-CLL and to autoimmune disease in spontaneous murine model.

The frequent occurrence of autoimmune diseases in patients with B cell chronic lymphocytic leukemia (B-CLL) or in their family members suggests the involvement of related predisposing genetic factors in the two distinct disorders. Because the majority of B-CLL is of CD5 B cell type, and because the majority of CD5 B cells produces polyreactive autoantibodies, certain regulatory abnormalities in the proliferation and differentiation of CD5 B cells appear to be involved in B-CLL and autoimmune disease, respectively. In studies using MHC(H-2)-congenic New Zealand mouse strains, NZB(H-2d), NZW(H-2z) and NZB x NZW F1(H-2d/z), we found that while H-2d/z heterozygosity acts as one genetic predisposing element for autoimmune disease, by providing the element for abnormal differentiation of CD5 B cells, the H-2z/z homozygosity serves as one predisposition for B-CLL, by promoting the abnormal proliferation of CD5 B cells. Another non-MHC-linked genes were also involved in the aberrant proliferation of CD5 B cells, as determined by microsatellite DNA analysis. Among these, there was a single dominant NZW locus located on chromosome 6, closely linked to the locus for TNF receptor p55. Hence our mouse model provides an appropriate tool for studying the relationship between genetic factors predisposing to B-CLL and autoimmune diseases.

Aging↗
PubMed1997

Detection of large macrophage colony forming cells in the peripheral blood of patients with rheumatoid arthritis.

OBJECTIVE: To test for the presence of colony forming cells, that form large macrophage colonies (> 2.5 mm in diameter, > 10,000 cells), in the peripheral blood of patients with rheumatoid arthritis (RA) and to determine its association with the clinical and laboratory features of RA. METHODS: Peripheral blood mononuclear cells (PBMC) from 96 patients with RA and 20 healthy controls were assayed for in vitro colony formation. In addition, PBMC from 38 patients with other rheumatic diseases including systemic lupus erythematosus (SLE), progressive systemic sclerosis (SSc), and polymyositis/dermatomyositis (PM/DM); 23 patients with infectious inflammatory diseases were also assayed. RESULTS: Large macrophage colony forming cells were detected in the peripheral blood of 19% of patients with RA (18/96), but not in that of healthy controls. In addition, these cells were detected in the peripheral blood of 11 of the 38 patients with other rheumatic disease (7/13 SSc and 4/11 PM/DM), but not in the 23 patients with infectious diseases. In the patients with RA, interstitial lung disease was significantly more frequently observed among patients in whom colony forming cells were found than among those in whom they were not found (p < 0.001). CONCLUSION: Based on the size of the colonies they formed, the macrophage colony forming cells detected in patients with RA probably corresponded to primitive hematopoietic progenitor cells, defined as high proliferative potential colony forming cells (HPP-CFC). Our observations provide preliminary evidence of the appearance of HPP-CFC in the circulation during inflammation of RA, and during that in other rheumatic diseases such as SSc and PM/DM, and of the association of HPP-CFC with interstitial lung disease in patients with RA.

Adult↗
PubMed1996

Cryptic origin of SPAI, a plasma protein with a transglutaminase substrate domain and the WAP motif, revealed by in situ hybridization and immunohistochemistry.

SPAI, originally isolated as a sodium/potassium-ATPase inhibitor and now considered to be a proteinase inhibitor of unknown specificity based on its similarity to elafin (an elastase inhibitor), is a new type of plasma protein that has a transglutaminase substrate domain, which serves as an anchoring sequence to be covalently cross-linked at target sites. To determine the source of SPAI, we carried out in situ hybridization and immunohistochemistry using an antisense cRNA probe and an antiserum against recombinant SPAI, respectively. Since previous RNase protection analysis had indicated that SPAI mRNA is almost exclusively expressed in the porcine small intestine, we used its frozen sections for the staining. The lower crypt was decorated with both the cRNA probe and antiserum, indicating that SPAI is synthesized and secreted by the enteroendocrine cells located near the crypt base. The native form of SPAI was also characterized by Western blotting. This result together with the previous biochemical and molecular biological characterizations may set the stage for identifying the physiological roles of the conceptually very interesting protein SPAI.

Animals↗
PubMed1996

Stimulation by retinoids of the natriuretic peptide system of osteoblastic MC3T3-E1 cells.

The effects were examined of treatment with retinoids of osteoblastic MC3T3-E1 cells on the natriuretic peptide system that promotes the differentiation of osteoblastic cells. Northern blot analysis revealed high levels of mRNA for the retinoid X receptor beta (RXR beta) and moderate levels of mRNAs for retinoic acid receptors alpha (RAR alpha) and gamma (RAR gamma). Exposure of MC3T3-E1 cells to 1 microM retinoid caused increases in the levels of C-type natriuretic peptide (CNP) and natriuretic peptide receptor-C (NPR-C). The activity of natriuretic peptide receptor-B (NPR-B) was unchanged after the addition of retinoid to the culture system. These results suggest that retinoids might influence the metabolism of osteoblastic cells through regulation of the natriuretic peptide system.

Animals↗
PubMed1996

Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene.

Type I thanatophoric dysplasia (TD) is typically a lethal neonatal dwarfism, but a limited number of cases of type I TD cases survive more than one year, suggesting genetic heterogeneity. In this study, we analyzed the fibroblast growth factor receptor 3 (FGFR3) gene in 5 Japanese cases of type I TD with clinical symptoms ranging from lethal to long-survival. In every case, nucleotide sequence analysis of cDNA revealed a C to T transition at nucleotide 742 (C742T) in one allele of the FGFR3 gene, suggesting that type I TD is a rather homogeneous genetic condition, irrespective of clinical course. No association was found between C742T and C882T, although both nucleotides changes were from CpG dinucleotide in a near location.

Cell Line↗
PubMed1996

Inhibition of proliferation of chondrocytes by specific receptors in response to retinoids.

All-trans retinoic acid inhibited the proliferation of chondrocytes derived from rat xiphoid cartilage when added to the culture medium at 10(-10)-10(-8) M. Proliferation of mouse clonal osteoblastic cells was also inhibited to a significant extent by all-trans retinoic acid. However, no such inhibitory effects on rat smooth muscle cells and human fibroblasts were observed. Flow cytometric analyses of chondrocytes labeled with propidium iodide revealed that all-trans retinoic acid arrested chondrocytes at the G1 phase of the cell cycle. Since 9-cis retinoic acid, which is synthesized enzymatically from all-trans retinoic acid, also inhibited the proliferation of chondrocytes, we investigated the subtypes of retinoic acid receptors in chondrocytes. Northern blot analysis revealed high levels of mRNA for retinoid X receptor alpha (RXR alpha), moderate levels of mRNA for retinoic acid receptor gamma (RAR gamma), and low levels of mRNA for RAR alpha and RXR beta. The mRNA for RAR beta and RXR gamma were not detected. These results suggest that retinoids are associated with the inhibition of proliferation of chondrocytes via both families of nuclear receptors, namely, RARs and RXRs.

Animals↗
PubMed1996

Molecular cloning and sequence analysis of the chick melanocortin 1-receptor gene.

The chick melanocortin 1-receptor gene was isolated. It is found to be an intronless gene encoding a 314 amino acid protein, sharing 64% identity with mammalian counterparts. A cis-element responsible for melanocyte-specific transcription is found in its 5' upstream region. It is probable that the expression of the receptor in melanocytes is closely correlated with that of melanogenesis-related genes.

Amino Acid Sequence↗
PubMed1996

Stimulation by C-type natriuretic peptide of the differentiation of clonal osteoblastic MC3T3-E1 cells.

We examined the effects of C-type natriuretic peptide (CNP) and B-type natriuretic peptide receptor (NPR-B) system, which stimulates the intracellular production of cGMP, on osteoblastic differentiation using clonal murine calvarial MC3T3-E1 cells. CNP-like immunoreactivity was detected in the conditioned medium and in lysates of MC3T3-E1 cells. Exposure of cells to CNP caused an increase in the intracellular production of cGMP and the increase was dose-dependent, while ANP had no effect. These results imply that CNP regulates osteoblastic metabolism via NPR-B in an autocrine manner. Northern blot analysis revealed that treatment of MC3T3-E1 cells with CNP increased the steady-state levels of mRNAs for type-I collagen, cellular alkaline phosphatase (ALPase), and osteocalcin, which are well known as markers of osteoblastic differentiation. Our observations suggest the possibility that CNP functions as a local regulator of osteoblastic differentiation, acting via a cGMP-mediated pathway.

3T3 Cells↗
PubMed1996

Accelerated evolution in inhibitor domains of porcine elafin family members.

Through the analysis of the porcine gene encoding the elastase inhibitor elafin, we demonstrated that there are at least three closely related members of the elafin family, and their genes have arisen by accelerated evolution. A porcine genomic DNA library was screened with a previously cloned human elafin cDNA probe, and several positive clones were obtained that can be distinguished by a combination of restriction enzymes. Sequence analysis of these clones revealed the presence of three homologous members whose genes, all consisting of three exons and two introns, are almost identical except the exon 2 sequences encoding the inhibitor domain called "WAP motif"; the intron sequences are related to each other with sequence similarities of 93-98%, whereas the exon 2 sequences exhibited only 60-77% similarities among the three members. The extreme divergence in the exon 2 sequences compared to the highly conserved intron sequences may be generated by accelerated mutations confined in a short stretch of the genes following recent duplication events of a single ancestral gene. An RNase protection assay indicated that the messages of the elafin family members are abundantly expressed in the trachea and intestine, suggesting that the most likely selective forces for the accelerated evolution are extrinsic proteinases produced by invasive microorganisms.

Amino Acid Sequence↗
PubMed1996

In situ identification of messenger RNA of endothelial type nitric oxide synthase in rat cardiac myocytes.

The endothelial type nitric oxide synthase (NOS) termed as NOS-III has been demonstrated in various nonendothelial cells. Although NOS-III was recently found in the cardiac tissues, identification of the cells expressing NOS-III gene in the heart remains unknown. In this study, we compared the expression of NOS-III mRNA in various tissues of rats by Northern blot analysis using a homologous cDNA probe and identified the cell type by in situ hybridization histochemistry with a cRNA probe. NOS-III mRNA was found more abundantly in atria and ventricle than in other various tissues examined. NOS-III mRNA was intensely and specifically visualized in the cardiac myocytes as well as in the endothelial cells of the heart. No staining was seen with a sense cRNA probe. These results provide the first in vivo evidence for NOS-III mRNA in the cardiac myocytes and suggest its role in the regulation of cardiac functions.

Animals↗
PubMed1996

Angiotensin converting enzyme inhibitor normalizes vascular natriuretic peptide type A receptor gene expression via bradykinin-dependent mechanism in hypertensive rats.

We previously demonstrated that angiotensin converting enzyme (ACE) inhibitor normalizes the up-regulated gene expression of vascular natriuretic peptide type A (NP-A) receptor in hypertensive rats. To elucidate the mechanism, we examined the effect of angiotensin II receptor (AT1) antagonist (TCV-116) and bradykinin receptor (B2) antagonist (Hoe 140) on the NP-A receptor mRNA level in the aorta of genetically hypertensive rats (SHR-SP/Izm) using ribonuclease protection assay. The effect of ACE inhibitor on the NP-A receptor mRNA level was completely abolished by a concomitant administration of Hoe 140, while TCV-116 did not show any significant effect on the NP-A receptor mRNA level. These results suggest that bradykinin plays an important role in the regulation of the vascular NP-A receptor gene expression.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

CD40-mediated stimulation of B1 and B2 cells: implication in autoantibody production in murine lupus.

B1 cells usually show preferential responses to T cell-independent antigens. To ask whether B1 cells could respond to CD40-mediated stimulation for proliferation and differentiation, and whether CD40-mediated signals are involved in the production of autoantibodies by B1 cells, we compared responses to our newly established agonistic anti-mouse CD40 monoclonal antibody (mAb) between B1 and B2 cells from autoimmune-prone (NZB x NZW) F1 mice. Stimulation with this mAb induced a similar level of proliferative responses of both B1 and B2 cells, as well as an increase in expression of cell surface molecules I-A, CD54, CD23, CD80, and CD86. While co-stimulation with interleukin (IL)-4 markedly augmented proliferative as well as IgG1 and IgE antibody responses of both B and B2 cells, co-stimulation with IL-5 augmented proliferative and IgM antibody responses of only B1 cells. Splenic B1, but not B2 cells from young (NZB x NZW) F1 mice spontaneously produced substantial amounts of IgM including IgM anti-DNA antibodies, and the levels increased in case of stimulation with anti-CD40 mAb alone, or to a greater extent with the mAb plus IL-4 and IL-5. Collectively, these results indicate that splenic B1 cells from autoimmune (NZB x NZW) F1 mice have a comparable responsiveness to the CD40-mediated stimulation to that of B2 cells, which would be a potent regulatory mechanism involved in the spontaneous production of autoantibodies by B1 cells.

Animals↗
PubMed1996

Effects of transgenic mixed-haplotype MHC class II molecules A alpha d A beta z on autoimmune disease in New Zealand mice.

The MHC haplotype heterozygosity (H-2d/H-2z) acts as one major predisposing genetic element for autoimmune disease resembling systemic lupus erythematosus (SLE) in the F1 hybrid of NZB (H-2d) and NZW (H-2z) mice. To determine a possible role of mixed-haplotype A molecules, we introduced a transgene A beta z into H-2d/H-2d homozygous (NZB x NZW.H-2d)F1 mice, in which, compared with the original H-2d/H-2z heterozygotes, the incidence and titer of IgG anti-DNA antibodies, serum levels of nephritogenic retroviral gp70/anti-gp70 immune complexes (ICs) and the associated incidence of IC-type lupus nephritis were reduced. Evidence for the formation of mixed-haplotype A alpha d A beta z molecules in the transgenic mice was obtained by A beta z molecule expression on the cell surface of splenic B cells and macrophages, thymic epithelial cells and mature B cells in the bone marrow. A alpha d A beta z-restricted T cell clones showed good proliferative responses to spleen cells from the transgenic mice, to an extent much larger than seen in cells from the original (NZB x NZW)F1 mice, suggesting that the expression of functional A alpha d A beta z molecules on cells in transgenic mice is considerably high. Compared with findings in transgene-negative littermates and the original (NZB x NZW)F1 mice, the A beta z transgene to a greater extent promoted serum levels of IgM anti-double-stranded (ds) DNA antibodies and IgM anti-gp70/gp70 ICs in the transgenic mice. None the less, the production of IgG anti-dsDNA antibodies and IgG anti-gp70/gp70 ICs as well as the development of renal disease was markedly suppressed. Possible mechanisms of such effects of the transgene are discussed.

Animals↗
PubMed1996

Change in the expression of C-type natriuretic peptide and its receptor, B-type natriuretic peptide receptor, during dedifferentiation of chondrocytes into fibroblast-like cells.

Chondrocytes derived from rat xiphoid cartilage dedifferentiated into fibroblast-like cells as the number of passages of the cells in culture increased. During in vitro dedifferentiation the growth of the cells was markedly suppressed. We had proposed previously that C-type natriuretic peptide (CNP) might be a potent antimitogenic factor for chondrocytes, and TGF-beta 1 induced a marked increase in CNP secretion of chondrocytes. Therefore, we investigated the expression of CNP, B-type natriuretic peptide receptor (NPR-B or GC-B), and TGF-beta 1 in this process. Radioimmunoassay and RNase protection analyses revealed passage-associated increase in CNP-like immunoreactivity and in levels of NPR-B mRNA, respectively. Northern blot analyses showed that the level of TGF-beta 1 mRNA decreased with increasing passage number. These results suggest that the expression of CNP and NPR-B might be involved in in vitro dedifferentiation of chondrocytes and TGF-beta 1 does not affect the increasing level of CNP during in vitro dedifferentiation.

Animals↗