Genomic organization and promoter analysis of mouse follistatin-related gene (FLRG).

Follistatin (FS) is well characterized as an activin-binding protein. Recently, a novel follistatin-like protein called follistatin-related gene (FLRG) that has a similar domain organization to that of follistatin has been identified. Like follistatins, FLRG binds activins and bone morphogenetic proteins (BMPs).

Changes in distribution of the long form of type XII collagen during chicken corneal development.

The expression and distribution of the long form of Type XII collagen were investigated histochemically during chicken corneal development using a monoclonal antibody (P3D11) raised against the N-terminal domain of chicken Type XII collagen. Specificity of the antibody was confirmed by immunoprecipitation before and after bacterial collagenase digestion. Immunofluorescent microscopic studies showed that during chicken cornea formation, the long form of Type XII collagen is initially detected on Day 3 embryo (stage 19) in the sub-epithelial matrix of the corneal periphery and in the matrix around the optic cup.

Potent DNA photocleavage by zinc(II) complexes of cationic bis-porphyrins linked with aliphatic diamine.

We have prepared zinc(II) complexes of cationic bis-porphyrins, as one of the attempts to improve less DNA photocleavage activities of the metal-free bis-porphyrins composed of two H(2)TMPyP-like chromophores, linked with a series of aliphatic diamines. The less activities seemed to be derived from their intermolecular self-aggregation properties in aqueous solution. The zinc(II) insertion into the metal-free cationic bis-porphyrins completely removed their self-aggregation properties, most probably due to steric hindrance between axial ligands of zinc(II) chromophores of the cationic bis-porphyrins.

The rasGAP-binding protein, Dok-1, mediates activin signaling via serine/threonine kinase receptors.

Activins, members of the transforming growth factor-beta family, are pleiotropic growth and differentiation factors. Activin A induces B-cell apoptosis. To identify the genes responsible for activin-induced apoptosis, we performed retrovirus-mediated gene trap screening in a mouse B-cell line.

Enantioselective adsorption of phenylalanine onto self-assembled monolayers of 1,1'binaphthalene-2,2'-dithiol on gold.

Self-assembled monolayer of atropisomeric compound, 1,1'-binaphthalene-2,2'-dithiol (BNSH), provides a field for chiral discrimination. The two-dimensional chiral arrangement with screw-like units, each of which is composed of three BNSH molecules, plays an important role in the enantioselectivity of adsorption of phenylalanine, as revealed by a quartz crystal microbalance technique.

[Transient myelodysplasia associated with human parvovirus B19 infection in a child without underlying disease].

Human parvovirus B19 (HPV-B19) infection is known to frequently induce aplastic crisis in patients with hemolytic anemia, but rarely causes hematological disorders in healthy subjects. We report a 5-year-old boy who showed transient myelodysplasia associated with HPV-B19 infection. He was admitted with severe nasal bleeding, and laboratory data showed marked thrombocytopenia (1,000/microliter), anemia (Hb: 8.

Solution properties and photonuclease activity of cationic bis-porphyrins linked with a series of aliphatic diamines.

The development of efficient photo-induced DNA cleavage agents has been of particular interest for biomedical applications such as cancer photodynamic therapy (PDT). Toward this objective, we synthesized a series of cationic bis-porphyrins with various lengths of diamino alkyl linkage, N,N'-bis[4-[10,15,20-tris(1-methylpyridinium-4-yl)porphyrin-5-yl]benzoyl]oligomethylenediamine hexaiodide. They were expected to show more efficient photocleavage of DNA than unichromophore meso-tetrakis(4-N-methylpyridiniumyl)porphine (TMPyP), which is well known to cleave DNA effectively on illumination.

Intracellular and extracellular control of activin function by novel regulatory molecules.

Activin signal transduction is regulated through multiple mechanisms. We have identified novel regulatory proteins that control activin functions either intracellularly or extracellularly. As intracellular molecules, PSD-95/Dlg/ZO-1 (PDZ) proteins that specifically associate with activin type II receptors (ActRIIs) were identified.

Differential gene expression of beta-1,4-galactosyltransferases I, II and V during mouse brain development.

Since most brain glycoproteins from beta-1,4-galactosyltransferase (beta-1,4-GalT) I knockout mice were galactosylated without apparent reduction the gene expression of novel beta-1,4-GalTs II and V which are involved in N-linked oligosaccharide biosynthesis in addition to beta-1,4-GalT I was studied during mouse brain development. Isolation and characterization of beta-1,4-GalT II and V cDNAs from mouse brains indicates that they are also functioning in the brain. Northern blot analysis revealed that the beta-1,4-GalT I gene is expressed mainly in mid-embryonic stages, while the expression level of beta-1,4-GalT II transcript remains constant and of beta-1,4-GalT V transcript increases during mouse brain development after birth.

Molecular Biological Analysis of Retinal and Streptococcal Heat-shock Protein 60.

Purpose: The observation of recurrent oral aphtha preceding ocular inflammation in patients with Behçet's disease suggests a role of oral Streptococcus in the etiology of this disease. Heat-treated Streptoccus antigen can induce ocular inflammation or systemic symptoms in Behçet's disease patients. Furthermore, the presence of an autoantibody against retinal heat-shock protein 60 (HSP 60) has been detected in the sera of these patients.

Interaction between inflammatory cells and heparin-surface-modified intraocular lens.

Purpose: To investigate the interaction and adherence of inflammatory cells to a heparin-surface-modified intraocular lens (HSM IOL).

Setting: Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan.

Methods: Splenic mononuclear leukocytes from rats with experimental autoimmune uveitis were cultured with the optic of an HSM IOL for 96 hours.

Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-beta family.

Follistatin is an activin-binding protein that prevents activin from binding to its receptors and neutralizes its activity. Follistatin also binds bone morphogenetic proteins (BMPs). In this study, we report the identification of a novel follistatin-like protein from mouse.

A cellular variant of supratentorial hemangioblastoma.

Supratentorial hemangioblastomas are rarely seen, especially in children and adolescents. We report the case of a 17-year-old male with supratentorial hemangioblastoma. Neuroimaging demonstrated a cystic lesion within the right parietal lobe.

Analysis of the role of egg integrins in sperm-egg binding and fusion.

Sperm-egg fusion is believed to be mediated via specific molecular interactions. Integrin alpha6beta1 is a strong candidate for a sperm receptor on the egg plasma membrane. However, the ability of the egg integrin alpha6beta1 to interact with molecules on intact sperm has not yet been proven.

[Molecular biological analysis of retinal and streptococcal heat-shock protein 60].

Purpose: The observation of recurrent oral aphtha preceding ocular inflammation in patients with Behçet's disease suggests a role of oral Streptococcus in the etiology of this disease. Heat-treated Streptococcus antigen can induce ocular inflammation or systemic symptoms in Behçet's disease patients. Furthermore, the presence of an autoantibody against retinal heat-shock protein 60 (HSP 60) has been detected in the sera of these patients.

Expression of a TGF-beta1 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines.

TSC-36 (TGF-beta1-stimulated clone 36) is a TGF-beta1 inducible gene whose product is an extracellular glycoprotein that contains a single follistatin module. TSC-36 is highly expressed in the lung, but its physiological function is unknown. In an attempt to elucidate it, we investigated the effect of TSC-36 on proliferation of human lung cancer cell lines.

Identification and characterization of a PDZ protein that interacts with activin type II receptors.

We have identified a mouse PDZ protein that interacts with the activin type IIA receptor (ActRIIA), which we named activin receptor-interacting protein 1 (ARIP1). By using yeast two-hybrid screening, we isolated a cDNA clone of ARIP1 from a mouse brain cDNA library. We detected two forms of ARIP1, ARIP1-long and ARIP1-short, which may be produced by alternative splicing.

Steroid sensitivity and postoperative course of seven patients with Behçet's disease.

Systemic administration of steroids to patients with Behçet's disease in Japan is often followed by a worsening in ocular symptoms. The sensitivity of 7 patients with Behçet's disease to steroids which were administered during and after intraocular surgery was therefore measured, and their postoperative course was reviewed. Three of the 7 showed a low steroid sensitivity, and the frequency of postoperative inflammatory episodes and the intraocular pressure were both higher for this group than for the 4 who showed high steroid sensitivity.

Behçet's disease and antibody titers to various heat-shock protein 60s.

It has been suggested that the 65 kDa heat-shock protein (HSP) of Streptococcus in recurrent aphthae within the oral cavity may be involved in the uveoretinitis of Behçet's disease, possibly through sensitization of the immune system. To investigate this possibility, we examined serum antibody titers for various members of the 60 kDa family of HSPs and their implications with regard to a role for HSP60s in Behçet's disease. We isolated HSP60 of Streptococcus pyogenes from the margin of oral aphthae in one Behçet's disease patient with severe uveoretinitis and the HSP60s of Yersinia enterocolitica, retinoblastoma cell line clone Y79, and bovine retinal extract and investigated the reaction of each of these HSP60s with 100-fold diluted serum samples from 20 Behçet's disease patients using anti-HSP60 antibody titers determined by ELISA.

A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 to irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues.

A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation.

We examined the effect of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated to have a potent ameliorating effect on acute graft-versus-host disease (GVHD), and on the graft-versus-leukaemia (GVL) effect of allogeneic bone marrow transplantation (BMT). KB-R7785 was administered to (C57BL/6 x BALB/c) F1 (CBF1) mice that had been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumour, along with or without transplantation of C57BL/6 (B6) bone marrow cells and spleen cells (BMS). Administration of KB-R7785 without BMS significantly prolonged the survival of B53-inoculated CBF1 mice by inhibiting the infiltration of B53 cells into the liver and spleen.

[Suppression of experimental autoimmune uveoretinitis with a combination of cyclosporin and allopurinol].

Purpose: We assessed the suppressive effect of a combination of cyclosporin (an immunosuppressive agent) and allopurinol (a xanthine oxidase inhibitor and radical scavenger) on experimental autoimmune uveoretinitis (EAU) in Lewis rats, induced by interphotoreceptor retinoid-binding protein (IRBP).

Methods: After the immunization of Lewis rats with 30 micrograms of IRBP. We administrated cyclosporin and/or allopurinol to the IRBP-immunized Lewis rats.

[Association of heat-shock protein and uveitis].

Heat-shock protein 60 derived from Yersinia enterocolitica (Yersinia HSP 60) and bovine retinal HSP (Retina HSP 60) were previously identified by immunological cross-reaction and a high degree of common antigenicity, and a specific antibody against both proteins was detected in the sera of uveitis patients. We report here an attempt to isolate and purify Retina HSP 60 and Yersinia HSP 60. Both Retina HSP 60 and Yersinia HSP 60 showed an enriched content of glycine of approximately 60 to 80%.

Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha antibodies on acute graft-versus-host disease pathologies.

Both tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD). In this study, we examined the ameliorating effects of neutralizing anti-FasL and/or anti-TNFalpha monoclonal antibody (MoAb) in a lethal acute GVHD model in mice. Whereas the treatment with either anti-FasL or anti-TNFalpha MoAb alone significantly delayed the mortality and improved the body weight, a complete protection was achieved by the administration of both MoAbs.

[Measurement of thrombomodulin values in the serum and eyes of experimental autoimmune uveoretinitis].

Thrombomodulin (TM) is a protein, present on intact endothelial cell surfaces, that plays a major role in the protein C anticoagulant system. Plasma TM is produced by injured endothelium, and is recognized in circulating blood or urine as a sign of endothelium cell damage. The localization of TM within the eye and its kinetics in the eye and the serum were investigated in rats with experimental autoimmune uveoretinitis (EAU).