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Biomedical subjects

A Shirai

Publications and source records attributed to A Shirai.

At least 37 records · Page 2Linked to original sources
PubMed1999

[A case of Sjögren's syndrome with retrobulbar optic neuritis and cutaneous vasculitis].

A 52-year-old woman, diagnosed as having Sjögren's syndrome by parotid sialography and lip biopsy after a two years history of recurrent purpuric rashes on her lower extremities, was admitted to our hospital because of visual disturbance in March 1998. On presentation at the department of ophthalmology, her right visual acuity was light perception, and laboratory findings showed elevated levels of antinuclear antibody and anti-Ro/SS-A and anti-La/SS-B antibodies. Cerebrospinal fluid analysis showed mild pleocytosis and elevated levels of total protein and Q-albumin. The IgG-index was within normal level and no oligoclonal band was found. Magnetic resonance imaging showed increased signal intensity at the right optic nerve. After treatment with m-PSL pulse therapy, her visual acuity recovered to 0.08. When prednisolone was gradually tapered to the dose of 30 mg per day, she was transferred to our department because of high grade fever and pancytopenia. She also suffered from palpable purpura in her extremities extending the trunk, whose pathological diagnosis was leukocytoclastic vasculitis. The immunohistochemical examination showed depositions of IgG and C1q. After two additional cycles of mPSL pulse therapies, clinical improvement was achieved. The titers of von Willebrand factor and thrombomodulin correlated with her clinical improvement. Patients with Sjögren's syndrome can develop extra-grandular complications, including neurologic and cutaneus diseases, it is important to understand the role of SS-A-B antibodies in the immunopathogenesis of Sjögren's syndrome.

Female↗
PubMed1998

Influenza A virus infection increases IgE production and airway responsiveness in aerosolized antigen-exposed mice.

BACKGROUND: Respiratory viral infection is known clinically to promote sensitization to antigen inhalation and the development of asthma. OBJECTIVE: The purpose of this investigation was to determine whether influenza type A virus infection enhances inhalation sensitization and increases airway responsiveness in mice. METHODS: Mice were infected by intranasal inoculation with influenza A viruses (strains: H1N1 and H3N2) or PBS. Animals were exposed to aerosols of ovalbumin on day 3. Two weeks after ovalbumin sensitization, mice were challenged with ovalbumin aerosols; 24 hours later, airway responsiveness (AR) to inhaled methacholine, levels of ovalbumin-specific IgE, and bronchoalveolar lavage fluid (BALF) were examined. RESULTS: Neither influenza A virus (H1N1 nor H3N2) alone nor ovalbumin sensitization alone caused changes in AR or IgE. However, ovalbumin sensitization after inoculation with either influenza A virus increased AR and levels of ovalbumin-specific IgE. On BALF-cell analysis, ovalbumin sensitization after inoculation with influenza virus A increased the number of lymphocytes but not the number of eosinophils. No difference in AR or IgE levels was observed between the 2 strains of influenza A viruses. Immmunostaining of BALF cells showed an increase in T cells, especially CD8(+) cells, with ovalbumin sensitization after inoculation with influenza virus A. CONCLUSION: Infection by influenza A virus enhances sensitization to inhaled antigens and airway responsiveness in mice by means of mechanisms including CD8(+) cells and antigen-specific IgE.

Acute-Phase Reaction↗
PubMed1998

Hair follicle elongation in organ culture of skin from newborn and adult mice.

By means of skin organ culture, some biological characteristics of hair follicle elongation were examined. When skin sections from 6-day-old C3H mice were cultured, spontaneous elongation of hair follicles was maintained. Without insulin, hair follicle elongation was poorly maintained irrespective of the presence of serum at 20%. Insulin could be replaced by IGF-I at 100 ng/ml. During in vitro elongation of hair follicles, bromodeoxyuridine was incorporated into germinal epithelial cells around dermal papillae. Skin sections from 4-week-old C3H mice did not show hair follicle elongation in complete medium. However, when 0.5 mM minoxidil was added to the medium, concentration dependent thickening and elongation of hair follicles was observed. In contrast, in vitro elongation of newborn pelage hair follicles was not enhanced by minoxidil. These results suggest that this system with the use of skin sections from 4-week-old C3H mice would be a potential in vitro model of human androgenic alopecia in which the anagen phase is suppressed but the suppression is partially released by minoxidil.

Aging↗
PubMed1996

Polyunsaturated fatty acid biosynthesis in Saccharomyces cerevisiae: expression of ethanol tolerance and the FAD2 gene from Arabidopsis thaliana.

The Arabidopsis thaliana delta-12 fatty acid desaturase gene (FAD2) was overexpressed in Saccharomyces cerevisiae by using the GAL1 promoter. S. cerevisiae harboring the FAD2 gene was capable of forming hexadecadienoyl (16:2) and linoleoyl (18:2) residues in the membrane lipid when cultured in medium containing galactose. Gas-liquid chromatography analysis of total lipids indicated that the transformed S. cerevisiae accumulated these dienoic fatty acyl residues and that they accounted for approximately 50% of the total fatty acyl residues. Phospholipid analysis of this strain indicated that the oleoyl (18:1) residue binding phosphatidylcholine (PC) was mostly converted to the 18:2 residue binding PC, whereas 50% of the palmitoleoyl (16:1) residue binding PC was converted to the 16:2 residue binding PC. A marked effect on the unsaturation of 16:1 and 18:1 was observed when S. cerevisiae harboring the FAD2 gene was cultured at 8 degrees C. To assess the ethanol tolerance of S. cerevisiae producing polyunsaturated fatty acids, the cell viability of this strain in the presence of ethanol was examined. The results indicated that S. cerevisiae cells overexpressing the FAD2 gene had greater resistance to 15% (vol/vol) ethanol than did the control cells.

Arabidopsis↗
PubMed1996

[Successful therapy with cyclosporine in a case with interstitial pneumonitis associated with polymyositis].

We describe a case of interstitial pneumonitis associated with polymyositis who responded well to cyclosporine therapy. In October, 1993, a 49-year-old female was admitted to our hospital because of fever, muscle weakness and progressive dyspnea. Interstitial pneumonitis with polymyositis was diagnosed and daily oral steroid therapy was started. As the therapy was ineffective, pulse intravenous steroid therapies followed by oral cyclophosphamide and steroid therapy was given. Whereas serum levels of muscle enzymes decreased, she became progressively hypoxemic. No effect was observed in series of therapy including additional pulse steroid therapy, pulse intravenous cyclophosphamide therapy, oral azathioprine and oral bethametazone therapy. In April, 1994, oral cyclosporine was started. After daily oral cyclosporine was combined with steroid, her symptoms, chest X-ray, chest CT and pulmonary function tests significantly improved. Her disease became stable and there was no signs of recurrence since then. It is suggested that cyclosporine is useful for the treatment of progressive interstitial pneumonitis associated with polymyositis.

Cyclosporine↗
PubMed1995

IgE receptor-positive non-B/non-T cells dominate the production of interleukin 4 and interleukin 6 in immunized mice.

The phenotype and antigenic specificity of cells secreting interleukin (IL) 4, IL-6, and interferon gamma was studied in mice during primary and secondary immune responses. T lymphocytes were the major source of interferon gamma, whereas non-B/non-T cells were the dominant source of IL-4 and IL-6 in the spleens of immunized animals. Cytokine-secreting non-B/non-T cells expressed surface receptors for IgE and/or IgG types II/III. Exposing these cells to antigen-specific IgE or IgG in vivo (or in vitro) "armed" them to release IL-4 and IL-6 upon subsequent antigenic challenge. These findings suggest that non-B/non-T cells may represent the "natural immunity" analogue of CD4+ T helper type 2 cells and participate in a positive feedback loop involved in the perpetuation of T helper type 2 cell responses.

Animals↗
PubMed1995

Increased activation and altered ratio of interferon-gamma: interleukin-4 secreting cells in MRL-lpr/lpr mice.

Cytokine specific ELIspot assays were used to monitor the number of cells secreting IL-4 and IFN gamma in MRL-lpr/lpr mice of different ages. The cytokine repertoire expressed by MRL-lpr/lpr mice was skewed towards the over-production of IFN gamma (and away from IL-4) when compared to that of MRL-+/-/+/- and BALB/c mice. With increasing age and disease severity, the ratio of IFN gamma: IL-4 secreting cells rose in MRL-lpr/lpr mice but decreased in normal animals. This changing ratio of IFN gamma: IL-4 secreting cells correlated with changes in the ratio of IgG2a: IgG1 secreting cells in these mice. Our findings suggest that cytokine secreting CD4+ and CD8+ cells are hyperactivated in young MRL-lpr/lpr mice, and that disease progression is associated with a disruption in the normal ratio of Th1:Th2 production in vivo.

Age Factors↗
PubMed1995

[Optic neuropathy in systemic lupus erythematosus (SLE)--analysis of 54 cases including our case].

A 46-year old woman with systemic lupus erythematosus (SLE) who had been treated with oral administration of prednisolone (7.5 mg/5 mg on alternate days) at our outpatient clinic suddenly developed a loss of visual acuity, visual field defect, and photophobia on Dec. 15th, 1993. When she was admitted three days later, she was diagnosed as having optic neuropathy, and immediate treatment with methylprednisolone (1 g/day for three days) followed by prednisolone (50 mg/day) resulted in complete disappearance of the above symptoms by Feb. 9th, 1994. As far as we know, fifty-three cases of SLE with optic neuropathy have been reported previously. The result of analysis of the 54 cases including our case indicates that rapid diagnosis and corticosteroid treatment in an early phase of optic neuropathy leads to significant improvement.

Female↗
PubMed1994

NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene.

Expression of the human monocyte chemoattractant protein-1 (hMCP-1) is ubiquitous in various cell types and is increased by a wide variety of stimuli. We initially found that the effects of various stimuli, including IL-1 beta, TNF-alpha, and 2-O-tetradecanoylphorbol 13-acetate, on the expression of hMCP-1 mRNA were quite different among A172 glioblastoma cells, HT1080 fibrosarcoma cells, and SKLMS1 leiomyosarcoma cells. These findings suggested that hMCP-1 expression is regulated both in a stimulus-specific and a tissue-specific manner. To elucidate the mechanism underlying this stimulus-specific and tissue-specific regulation, we isolated a hMCP-1 5'-flanking genomic DNA fragment and sequenced it extensively up to bp 3011 upstream from the transcriptional start site. Among many putative cis-elements, we identified two cis-elements critical for the transcription of the hMCP-1 gene. The first element is a remote kappa B binding site located far upstream between bp -2612 and -2603 that was important for IL-1 beta-, TNF-alpha-, and 2-O-tetradecanoylphorbol 13-acetate-induced enhancer activity. Mutation at the kappa B consensus site resulted in a complete loss of these stimulus-induced enhancer activities. The second element is a GC box located between bp -64 and -59 that was important for the maintenance of basal transcriptional activity. Overexpression of rSp1 resulted in increased hMCP-1 transcriptional activity, possibly suggesting the role of Sp1 in controlling basal hMCP-1 transcription via this GC box. These results together indicate that hMCP-1 expression is controlled by at least two distinct regulatory elements: a kappa B site and a GC box that seem to be associated with stimulus-specific and tissue-specific regulation, respectively.

Base Sequence↗
PubMed1994

Treatment with dextran-conjugated anti-IgD delays the development of autoimmunity in MRL-lpr/lpr mice.

The onset of clinical disease in autoimmune MRL-lpr/lpr mice is preceded by a switch from predominantly IgM production to IgG production. Previous studies have shown that IgG autoantibodies play a central role in the development of life-threatening glomerulonephritis in this strain. Delaying or preventing the switch from IgM to IgG production might therefore be of therapeutic benefit. We previously documented similarities in the B cell repertoire expressed by young MRL-lpr/lpr mice and normal mice treated with the polyclonal activator LPS. Recent in vivo studies indicate that cross-linking membrane IgM or IgD can suppress LPS-dependent IgG production in normal animals. These observations led us to examine whether membrane cross-linking could also lower serum IgG levels in MRL-lpr/lpr mice. Lupus-prone animals were treated with multivalent anti-IgD conjugated to high m.w. dextran. This anti-IgD dextran conjugate was previously shown to reduce IgG production in LPS-stimulated normal animals. Treatment of young lupus-prone MRL-lpr/lpr mice resulted in a significant reduction in the total number of B cells secreting IgG and lower serum titers of IgG anti-DNA and IgG anti-histone autoantibodies. Anti-IgD dextran treatment also delayed the development of glomerulonephritis and improved survival. Thus, anti-IgD dextran interfered with autoantibody-dependent disease progression, perhaps by inhibiting the switch from IgM to IgG autoantibody production.

Age Factors↗
PubMed1994

Transport of cyclosporin A across the brain capillary endothelial cell monolayer by P-glycoprotein.

P-glycoprotein, a multidrug transporter protein, exists in the brain capillary endothelium. To study the function of P-glycoprotein in brain capillary endothelium as a barrier against cyclosporin A, we examined the interaction of cyclosporin A with P-glycoprotein expressed in cultured brain capillary endothelial cells (MBEC4). P-glycoprotein of MBEC4 specifically bound [125I]iodoaryl azidoprazosin, and the binding was inhibited by cyclosporin A and vincristine. Intracellular accumulation of cyclosporin A in MBEC4 was about one-third the amount accumulated in mouse aortic endothelial cells (MAEC3), a cell line that did not express P-glycoprotein. The reduced accumulation of cyclosporin A in MBEC4 was increased by verapamil, a competitive inhibitor of transport function of P-glycoprotein. Cyclosporin A was preferentially transported from basal to apical side when the cell monolayer of MBEC4 was formed; however this transendothelial transport was not observed across cell monolayer of MAEC3. Verapamil inhibited the transendothelial transport of cyclosporin A across the MBEC4 monolayer. Thus P-glycoprotein in brain capillary endothelium could transport cyclosporin A across the endothelium from the basal to the apical side. These observations suggest that P-glycoprotein is involved in the complex function of the blood-brain barrier as a secretory detoxifying transporter of cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Cross-reactivity of IgG anti-DNA-secreting B cells in patients with systemic lupus erythematosus.

This study is the first to analyze the cross-reactivity of in vivo activated B cells from patients with systemic lupus erythematosus. A chamber ELIspot assay was used to determine whether lymphocytes secreting antibodies that bound to DNA or 2,4,6-trinitrophenol (TNP)-keyhole limpet-hemocyanin (KLH) could simultaneously bind to the unrelated antigens actin or ovalbumin. IgM anti-DNA-, IgM anti-TNP-KLH- and IgG anti-TNP-KLH-secreting B cells from patients and controls showed similar levels of cross-reactivity (ranging from 6% to 23%, depending upon the antibody isotype and antigen pair examined). In general, IgG-producing cells were less cross-reactive than IgM producers from the same individual (on the average threefold, p < 0.001). In contrast, IgG anti-DNA-secreting B cells from lupus patients (i) showed no decrease in cross-reactivity when compared to IgM anti-DNA-secreting cells and (ii) were significantly more cross-reactive than control IgG anti-DNA-secreting cells and IgG anti-TNP-KLH secreting cells from patients (p < 0.001). The degree of IgG anti-DNA cross-reactivity correlated with disease activity (r = 0.52, p < 0.02). The implications of these findings with respect to repertoire expression and disease pathogenesis are discussed.

Adult↗
PubMed1994

Cross-reactivity of IgM- and IgG-secreting B cells in murine chronic graft-versus-host reaction.

A chamber ELISpot assay was used to measure the frequency with which in vivo activated B cells secreted cross-reactive antibodies during a chronic graft-versus-host reaction in mice. Both normal (C57BL/10 x DBA/2)F1 mice and F1 recipients of syngeneic spleen cells (SynF1) expressed repertoires in which 13-17% of IgM and 3-5% of IgG-secreting cells were cross-reactive. By comparison, 43-55% of IgM and 9-40% of IgG-secreting cells from F1 recipients of parental DBA/2 spleen cells (GVHF1) were cross-reactive (P < 0.01, GVHF1 versus F1 or SynF1). The cross-reactivity of the GVHF1 IgM secreting cells remained elevated for > 2 months following cell transfer. In contrast, the cross-reactivity of IgG-secreting cells, which was significantly high at Week 3 post-transfer, declined to nearly normal levels by Week 9. These findings demonstrate that cross-reactive B cells constitute an abnormally large fraction of the repertoire expressed by mice with chronic GVHR in a period when B cell hyperstimulation was occurring.

Animals↗
PubMed1994

Biosynthesis of a novel polysaccharide by Acetobacter xylinum.

An Acetobacter xylinum adapted to a medium containing N-acetylglucosamine (GlcNAc) has been used to prepare a novel polysaccharide containing residual GlcNAc in cellulose. The maximum amount of incorporation was found to be 4 mol% in cellulose, when a mixed medium containing 1.4% glucose (Glc) and 0.6% GlcNAc was used for the culture of A. xylinum. The resulting polysaccharide was lysozyme-susceptible. The aminosugar residue incorporated into bacterial cellulose was found to be only GlcNAc, even if galactosamine (GalN) and glucosamine (GlcN) were applied, whereas there was little effect by mannosamine (ManN). As the major component of the resulting polysaccharide was Glc residues, even if the only carbon source in the culture medium was GlcNAc, it was suggested that there must be several enzyme systems to convert GlcNAc into Glc in the bacteria. Several ammonium salts were also found to be effective for the incorporation of GlcNAc residues when the incubation system was converted to rotatory and aerobic incubation from static incubation. The amount of residual GlcNAc was remarkably increased by the addition of lysozyme-susceptible phosphoryl-chitin (P-chitin) and increased slightly with addition of P-chitin that was less lysozyme-susceptible. However, little effect was found on addition of highly substituted P-chitin.

Acetylglucosamine↗
PubMed1994

Individual cells simultaneously produce both IL-4 and IL-6 in vivo.

IL-4 and IL-6 are pleiotropic cytokines that can act independently or synergistically to regulate lymphocyte growth and differentiation. Both of these factors are produced by cultures of Th2 cells but it is uncertain whether they are secreted simultaneously by a single cell. We used a sensitive and specific ELIspot assay to identify individual cells spontaneously producing IL-4 or IL-6 under physiological conditions in vivo. The fraction of cells producing these two lymphokines was regulated concurrently in cloned Th2 cells but varied independently in the lymphoid organs of normal BALB/c mice. A sandwich ELIspot assay was developed to determine whether individual cells simultaneously produced both cytokines. Thirteen per cent of cells in the spleen and 25% of those in the bone marrow of 10-week-old BALB/c mice secreting either IL-4 or IL-6 concurrently produced both of these lymphokines. These observations establish a physiological mechanism by which the concurrent production of synergistic cytokines is regulated in a given micro-environment.

Animals↗
PubMed1994

[A case of Listeria meningitis associated with systemic lupus erythematosus].

We report a case of Listeria meningitis associated with systemic lupus erythematosus (SLE). The case is a 29-year-old female who was diagnosed as SLE on August, 1982, and had been followed since then. On May 25, 1993, she was admitted to our hospital with complaints of fever, head ache and vomiting which developed 3 days before admission. An examination of the cerebro-spinal fluid (CSF) revealed a cell count of (3664/3/mm3), protein concentration (123 mg/dl), and the quotient of CSF (Q albumin) (27.5) were elevated. A diagnosis of meningitis was made and therapy of antibiotics was begun. A CSF culture on admission was positive for Listeria monocytogenes, but the blood culture was negative. Clinical symptoms disappeared in about a week and abnormal CSF findings returned to normal in about a month with the administration of antibiotics. Listeria infection is a rare disease, but sometimes develops as an opportunistic infection in immunocompromised hosts. As far as we know, only 13 cases have been reported so far (9 cases in foreign countries, 4 cases in Japan). We also discuss Listeria infections associsted with SLE referring to the former reports.

Adult↗