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Biomedical subjects

S Hirose

Publications and source records attributed to S Hirose.

At least 379 records · Page 21Linked to original sources
PubMed1992

Differential expression of a CD45R epitope(6B2) on murine CD5+ B cells: possible difference in the post-translational modification of CD45 molecules.

Although murine peritoneal B cells were homogenously positive for an epitope Lp-2, coded for by the alternative exon 4 of the CD45 gene, they were heterogenous with respect to the expression of another CD45R epitope, 6B2, of unknown exon dependency. While the majority of 6B2-high peritoneal B cells was composed of CD5- B cells, those with low or negative 6B2 were CD5+ B cells. Both 6B2+ and 6B2- peritoneal B cells expressed mainly the same largest CD45R transcripts, with all three alternative exon (4, 5, and 6) sequences. Further, a CD5+ B lymphoma cell line, BCL-1, which was found to be Lp-2+6B2- also had the largest isoform of CD45R molecules with all three alternate structures. Although enzyme digestion studies suggested that the 6B2 epitope resides in protein, not in sugar structures, it is likely that a post-translational modification of CD45R molecules is responsible for the presence or absence of 6B2 epitope expression on peritoneal CD5+ B cells. This event may be related to the differential role of CD45R molecules in regulating lymphocyte function.

Animals↗
PubMed1992

Heterozygosity of the major histocompatibility complex controls the autoimmune disease in (NZW x BXSB) F1 mice.

In the F1 hybrid of phenotypically normal NZW (H-2z) and systemic lupus erythematosus (SLE)-prone BXSB mice (H-2b), features of the disease became more severe than those seen in the BXSB mice, regardless of the presence or absence of the Yaa (Y-chromosome-linked autoimmune acceleration) mutant gene. To determine whether the gene(s) linked to the major histocompatibility complex (MHC) of NZW mice is involved in this event, we developed the H-2-congenic NZW.H-2d strain and compared the severity of autoimmune disease between (NZW x BXSB) F1 (H-2z/b) and (NZW.H-2d x BXSB) F1 mice (H-2d/b). The H-2z/b, but not H-2d/b, heterozygous F1 mice of both sexes showed an accelerated, higher incidence of proteinuria and a more severe thrombocytopenia than did the BXSB mice. In NZW x (NZW x BXSB) F1 backcross mice, the H-2z/b heterozygous progeny showed more severe disease than did the H-2z/z homozygotes. Thus, disease-accelerating events in (NZW x BXSB) F1 mice are linked to the H-2z/b heterozygosity. Because H-2d/z heterozygosity plays a crucial role for SLE in (NZB x NZW) F1 mice, in which SLE features differ from those in (NZW x BXSB) F1 mice, the present observations may imply that the different but related MHC heterozygosity acts as a predisposing genetic element in these different SLE syndromes.

Age Factors↗
PubMed1992

Differential expression of three CD45 alternative structures on murine T cells: exon 6-dependent epitope as a marker for functional heterogeneity of CD4+ T cells.

We prepared a novel rat mAb specific for CD45 molecules bearing the epitope coded for by the alternative exon 6 of the murine CD45 gene (CD45RC). Together with available mAbs to alternative exon 4- and 5-dependent epitopes (CD45RA and CD45RB respectively), we found that the three alternative exons show differential expressions on murine lymphocytes. Flow cytometry analysis revealed that although B cells were homogeneously CD45RA+B+C+, the CD4+ T cells clearly included two populations, CD45RA-B+C- and CD45RA-B+C+. The CD8+ T cells were separated into CD45RA-B+C+ and CD45RA+B+C+ populations. Such features of epitope expression on the cell surface correlate well with message levels of corresponding alternative exons. In the CD4+ T cells, messages of alternative exons were associated with either one or two exon forms of the CD45 transcript. In CD8+ T cells, there were transcripts with one, two, or three alternative exons. When stimulated by an immobilized CD3 mAb, the CD45RC+CD4+ T cell subset preferentially secreted IL-2 and CD45RC-CD4+ T cells produced IL-4. Upon stimulation with concanavalin A, CD45RC-CD4+ T cells converted to CD45RC+ cells, and the level of CD45RC expression on the CD45RC+CD4+ T cell subset was up-regulated. These changes were unidirectional and irreversible. Therefore, differential expression of CD45RC probably delineates the functional heterogeneity of murine CD4+ T cells that is associated with the stages of CD4+ T cell maturation or activation.

Amino Acid Sequence↗
PubMed1992

Structure of the bovine endothelin-B receptor gene and its tissue-specific expression revealed by northern analysis.

We have isolated and characterized the gene encoding the bovine endothelin (ET) receptor ETB with seven putative membrane-spanning domains. The gene exists as a single copy of the bovine genome and extends over 36 kilobases. The coding region is divided into seven exons separated by six introns; the first exon encodes the first and second transmembrane domains and each of the following transmembrane domains is encoded by a separate exon. The 5' region of the transcript was examined by the ribonuclease protection analysis; multiple start sites were deduced with no apparent "TATA" box in the expected upstream region. Northern blot analysis demonstrated a widespread but tissue-specific distribution of the ETB receptor in bovine tissues.

Amino Acid Sequence↗
PubMed1992

Regulation of Drosophila neural development by a putative secreted protein.

The Drosophila strawberry (sty) locus was isolated by P-element insertion mutagenesis in a screen for mutations affecting eye development. Analysis of the mutant phenotype and the putative expression pattern of the sty gene suggested that it has multiple functions. Mutations in the sty gene lead to irregular spacing of ommatidia, an increase in the number of photoreceptor cells, as well as abnormal axonal projections to the lamina and disrupted structure of the optic lobes in the adult fly. The sty mutation also causes abnormal head involution, a change in a number of sensilla in the antennomaxillary complex in the embryonic stage and abnormal morphogenesis of the maxillary palp and wings in later stages. We examined the presumptive expression of the sty gene during development by histochemical staining for lacZ expression from enhancer trap elements inserted within the sty gene. During embryogenesis, expression of lacZ showed a segmental pattern in the ectoderm and in the nervous system. In the eye imaginal discs, lacZ was expressed in photoreceptor cells beginning a few rows posterior to the morphogenetic furrow. The lacZ was also expressed in the wing disc. In the adult, lacZ was expressed in the retina and lamina. We cloned the sty gene by P-element tagging and found that it encodes a putative secreted protein containing a cysteine-rich region similar to the epidermal growth factor (EGF) repeat. On the basis of the loss of functional phenotype, the expression pattern and the predicted structure of its product, we propose that sty encodes a diffusible protein acting as a signal involved in lateral inhibition within the developing nervous system and also as a factor involved either directly or indirectly in axonal guidance and optic lobe development.

Animals↗
PubMed1992

The effect of nifedipine and dipyridamole on the Doppler blood flow waveforms of umbilical and uterine arteries in hypertensive pregnant women.

In a study of 45 hypertensive pregnant women, the systolic velocity/diastolic velocity ratio and pulsatility index of the umbilical and uterine arteries showed good correlation with the maternal blood pressure, and they appeared to provide a good parameter for the fetoplacental condition. Using the pulse Doppler method, we studied the effects of the antihypertensive agent nifedipine and of dipyridamole (an agent used to treat proteinuria) on the blood flow of the umbilical and uterine arteries in 16 hypertensive pregnant women. The results proved that both drugs caused a decrease in the vascular resistance of the umbilical artery and suggested that they increased the blood flow volume of this artery and were useful in the treatment of hypertension during pregnancy.

Adult↗
PubMed1992

A novel DNA-binding motif abuts the zinc finger domain of insect nuclear hormone receptor FTZ-F1 and mouse embryonal long terminal repeat-binding protein.

Fruit fly FTZ-F1, silkworm BmFTZ-F1, and mouse embryonal long terminal repeat-binding protein are members of the nuclear hormone receptor superfamily, which recognizes the same sequence, 5'-PyCAAGGPyCPu-3'. Among these proteins, a 30-amino-acid basic region abutting the C-terminal end of the zinc finger motif, designated the FTZ-F1 box, is conserved. Gel mobility shift competition by various mutant peptides of the DNA-binding region revealed that the FTZ-F1 box as well as the zinc finger motif is involved in the high-affinity binding of FTZ-F1 to its target site. Using a gel mobility shift matrix competition assay, we demonstrated that the FTZ-F1 box governs the recognition of the first three bases, while the zinc finger region recognizes the remaining part of the binding sequence. We also showed that the DNA-binding region of FTZ-F1 recognizes and binds to DNA as a monomer. Occurrence of the FTZ-F1 box sequence in other members of the nuclear hormone receptor superfamily raises the possibility that these receptors constitute a unique subfamily which binds to DNA as a monomer.

Amino Acid Sequence↗
PubMed1992

Embryonal long terminal repeat-binding protein is a murine homolog of FTZ-F1, a member of the steroid receptor superfamily.

The embryonal long terminal repeat-binding protein, ELP, is present in undifferentiated mouse embryonal carcinoma cells. It binds to and suppresses transcription of the Moloney leukemia virus long terminal repeat in undifferentiated murine embryonal carcinoma cells. We report here that ELP is a mouse homolog of Drosophila FTZ-F1, which positively regulates transcription of the fushi tarazu gene in blastoderm-stage embryos of the fly. As members of the steroid receptor superfamily, ELP and FTZ-F1 have both DNA binding and putative ligand binding domains which are well conserved between the two. ELP and FTZ-F1 function in cells in the extremely early stage of development. A high degree of conservation between the two transcription factors during the evolution of these species indicates the importance of their functions in early-stage embryogenesis. In addition, the sequence elements they recognize do not contain repeat units, in contrast to other steroid receptors, which usually bind to either palindromic or direct repeat sequences.

Amino Acid Sequence↗
PubMed1992

Immunoadsorbent plasmapheresis for a patient with antiphospholipid syndrome during pregnancy.

The case of a 34 year old woman with systemic lupus erythematosus with a history of three previous recurrent abortions and lupus anticoagulant and anticardiolipin antibodies is reported. Immunoadsorbent plasmapheresis with a dextran sulphate column was used to remove lupus anticoagulant, anticardiolipin antibodies, and antibodies to DNA during her fourth pregnancy in combination with low doses of aspirin and prednisolone. Although during the course of treatment prednisolone was transiently increased to 30 mg/day owing to an asymptomatic increase of lupus anticoagulant and anticardiolipin antibodies, the levels of lupus anticoagulant, anticardiolipin antibodies, and antibodies to DNA were decreased by immunoadsorbent plasmapheresis and a baby girl was delivered successfully by caesarean section. Therefore, immunoadsorbent plasmapheresis with dextran sulphate seems to reduce the risk of recurrent abortion in patients with the antiphospholipid syndrome.

Adult↗
PubMed1992

Autoantibodies to T and B cell lines detected in serum samples from patients with systemic lupus erythematosus with lymphopenia and hypocomplementaemia.

Antibodies to lymphocytes in serum samples from 88 patients with systemic lupus erythematosus (SLE) and 15 normal control subjects were examined by a cell enzyme linked immunosorbent assay (ELISA) with four human T and B cell lines as antigens. The antibodies reacted with the Wa B cell line and the T cell lines P12 (CD4-, CD8+), Jurkat (CD4-, CD8-), and Hut78 (CD4+, CD8-). Antibody titres in serum samples from patients with SLE were higher than in those from normal control subjects. Titres of antibodies to P12 were correlated with titres of antibodies to Wa, Jurkat, and Hut78 in serum samples from patients with SLE. IgG antibodies to P12 were associated with lymphopenia and reduced haemolytic complement. By thin layer chromatography immunostaining, the antibodies in serum samples from two of 10 patients with SLE with high titres of IgG antibodies to P12 and lymphopenia were shown to react with three monosialoglycosphingolipids and two neutral glycosphingolipids from P12 cells. Antibodies to lymphocytes in serum samples from patients with SLE react with T and B cell lines, recognise a series of cell membrane glycosphingolipids and are associated with the lymphopenia and hypocomplementaemia typical of active disease.

Adult↗
PubMed1992

Soluble interleukin 2 receptors in patients with polymyositis/dermatomyositis.

The concentration of soluble interleukin 2 receptor was determined in serum samples from 19 patients with polymyositis/dermatomyositis by an enzyme linked immunosorbent assay (ELISA). The concentration of soluble interleukin 2 receptor in serum samples from patients with polymyositis/dermatomyositis was higher than that in samples from normal subjects.

Adult↗
PubMed1992

Properties and localization of endothelin-1-specific receptors in rat testicles.

The characterization and localization of rat testicular endothelin receptors were studied. Receptor binding assay with radiolabeled members of the endothelin family revealed that endothelin-1-specific receptors were present in rat testes; a maximal binding capacity of 250 +/- 62 fmol/mg protein and a dissociation constant value of 0.35 +/- 0.06 nM were calculated from the Scatchard plot. The affinities for endothelin analogues were endothelin-1 = endothelin-2 much greater than endothelin-3 much greater big endothelin-1 for the membrane-bound receptors. Receptors of endothelin-1 were localized in peritubular myoid cells and interstitial cells of rat testis by 125I-labeled endothelin-1 autoradiography; the receptors were undetectable in spermatogenic cells. The presence of endothelin-1 receptors in the rat testis raises the possibility that one or more of the endothelins may play a physiological role in the regulation of testicular function.

Animals↗
PubMed1992

Beta-VLDL-induced cholesterol ester deposition in macrophages may be regulated by neutral cholesterol esterase activity.

We examined the role of enzyme activities involved in cholesterol ester metabolism in the accumulation of cholesterol ester in macrophages. When [3H]cholesterol linoleate-beta-very low density lipoproteins (beta-VLDLs) were incubated with rat resident peritoneal macrophages (RPMs), thioglycolate-elicited macrophages (TEMs), or alveolar macrophages (AMs), cholesterol ester accumulation was the greatest in TEMs and the least in AMs. The uptake of [3H]cholesterol linoleate-beta-VLDL into AMs was four times that into RPMs, and the uptake into TEMs was twice that into RPMs. The [3H]cholesterol released from [3H]cholesterol linoleate-beta-VLDL-loaded AMs was five times higher than from TEMs and RPMs, whereas those from RPMs and TEMs were almost the same. In studies using cell homogenates, the acid cholesterol esterase activity in AMs was 1.7 times that in TEMs and six times that in RPMs. The acyl-coenzyme A:cholesterol acyltransferase (ACAT) activities in AMs and TEMs were similar but were higher than that in RPMs. The neutral cholesterol esterase activity was seven times higher in AMs than in RPMs and TEMs. In the study using intact cells, the hydrolysis of loaded [3H]cholesterol linoleate-beta-VLDL in the presence of the ACAT inhibitor CL277,082 and the cholesterol [14C]oleate synthesis from [14C]oleate were enhanced in AMs about twofold compared with RPMs and TEMs. The reduction of de novo synthesized cholesterol [14C]oleate in the presence of CL277,082 was enhanced in AMs four times compared with TEMs or RPMs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Separation and some characteristics of two factors from rat liver particulate fraction which stimulate and inhibit the low-Km adenosine 3',5' cyclic monophosphate (cAMP) phosphodiesterase of rat fat cells.

Two factors were separated from rat liver particulate fraction treated with insulin, one of them having a stimulating effect on low-Km adenosine 3',5' cyclic monophosphate (cAMP) phosphodiesterase activity of crude microsomal fraction (P-2 fraction) and the other having an inhibiting effect on the activity of low-Km cAMP phosphodiesterase solubilized with 0.3% Brij 58 from P-2 fraction. Trypsin and heat treatments had essentially no effect on these two factors. The stimulating factor did not significantly change the apparent Km value of enzyme in P-2 fraction but increased the maximal velocity of the reaction. The inhibiting factor raised the Km value of solubilized enzyme without affecting the maximal velocity of the reaction. The stimulating factor level in diabetic rat was larger than that in normal rat while the inhibiting factor level in diabetic rat was smaller than that in normal rat. Possible participation of both factors in insulin action is discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Distribution and clinical significance of lupus anticoagulant and anticardiolipin antibody in 349 patients with systemic lupus erythematosus.

Samples from 349 patients with systemic lupus erythematosus (SLE) were tested simultaneously for lupus anticoagulant (LAC) and anticardiolipin antibodies (ACL). LAC was detected in 27.2% of 349 SLE patients by a modified mixing kaolin clotting time. ACL was detected in 34.7% by enzyme-linked immunosorbent assay. Only half of the patients who had LAC or ACL were positive for both of them. In addition, isotypes of ACL in these patients were studied. The IgG isotype was detected in 81.8% of 121 patients, and more than half had only the IgG isotype. When clinical features of patients with LAC or ACL were studied, the incidence of thrombosis, fetal loss, and thrombocytopenia were significantly higher in both groups compared with patients without LAC or ACL. In particular, the patients with both LAC and ACL showed the highest risk of fetal loss (89%) during pregnancy. These results indicate that LAC and ACL are detected in partly different groups of SLE patients, but both of these groups are clinically similar.

Antiphospholipid Syndrome↗
PubMed1992

Genetic association between natural autoantibody responses to histones and DNA in murine lupus.

Genetic regulation of the spontaneous anti-histone antibody production in systemic lupus erythematosus (SLE) was studied using the H-2-congenic and T cell receptor beta chain gene complex (TCR beta)-congenic NZB and NZW strains and their crosses. We found that the original, parental H-2d/d NZB mice produced significantly higher titers of serum IgM class anti-histone antibodies than did the congenic H-2d/z or H-2z/z NZB mice. However, none of these three NZB strains produced IgG antibodies. The NZW strain of any H-2 haplotype did not produce IgM and IgG anti-histone antibodies. The IgG anti-histone antibodies were produced only by H-2d/z heterozygous NZB x NZW F1, but not by homozygous H-2z/z or H-2d/d NZB x NZW F1 mice. In studies using (NZB x NZW) F1 x NZB backcross mice, only the progeny having both H-2d/z and NZW-type TCR beta genotypes produced high amounts of IgG antibodies. There was a tight linkage between the NZW-type TCR beta and the production of IgG anti-histone antibodies in TCR beta-congenic NZB x NZW F1 mice. All these findings were in keeping with our preceding observations on the genetic regulation of anti-DNA antibodies in these mice and suggest that certain common mechanisms such as super-antigen-mediated or common idiotope-mediated regulations may underlie the production of these two distinct autoantibodies in NZB x NZW F1 mice.

Animals↗
PubMed1992

An early activation antigen of murine T cells recognized by monoclonal natural autoantibody NTA204 and the expression on T cells from aged NZB x NZW F1 mice with overt autoimmune disease.

A monoclonal natural thymocytotoxic autoantibody NTA204 established from an autoimmune-prone NZB mouse reacted with the majority of thymocytes, all peripheral B cells, granulocytes and bone marrow myeloid cells, but not with peripheral resting T cells of normal mice. In aged NZB/W F1 mice with overt autoimmune disease, the population of NTA204+ CD4+ CD25- T cells was remarkably increased. The NTA204 antigen could be induced on splenic T cells from normal healthy mice as early as 3 hr after the initiation of culture with stimulant Con A, and was expressed on the vast majority in the 48-hr culture. The expression preceded that of other T cell activation antigens tested, CD25 and CD45R. Cell cycle analysis suggested that NTA204 is expressed at an early phase of G1A. T cells, particularly CD8+ T cells, in the allogeneic mixed lymphocyte culture (MLC) could be divided into two populations, NTA204+ and NTA204-. By immunohistochemical analysis, 30% of NTA204+ CD8+, but few NT204- CD8+ T cells were intensely positive for large cytoplasmic granules of perforin, an important cytolytic mediator of cytotoxic T cells. Thus the increased population of NTA204+ T cells in aged NZB/W F1 mice appear to be activated T cells and might be at least partly involved in the pathogenesis of disease in these mice. Immunoblotting analysis of Con A-activated splenic T cells showed that NTA204 molecules have a molecular mass of 49 Kd.

Animals↗