Abstract: An immune checkpoint inhibitor containing a substance that inhibits binding between fibronectin and an immunosuppressive receptor LILRB4 as an active ingredient, a therapeutic agent for an immune checkpoint-related disease, an immunosuppressant containing a substance that activates an immunosuppressive receptor LILRB4 as an active ingredient, an anti-fibronectin antibody or a derivative thereof, a fibronectin analog, a kit for detecting fibronectin or a partial protein thereof, and a method for detecting fibronectin or a partial protein thereof in a biological sample using the kit.

Abstract: A gasket includes a flexible packing portion having a recess attached to a coupler of a plunger rod, and a core member harder than the packing portion. The recess has an internal circumferential surface with an internally threaded portion capable of being screwed on and thus engaging with an externally threaded portion provided on an external circumferential surface of the coupler. The core member has a helical shape defining the internal circumferential surface of the recess and the internally threaded portion provided on the internal circumferential surface. The packing portion defines a sliding surface brought into contact with an inner circumferential surface of a barrel, and the packing portion also covers an outer circumferential surface of the core member.

Abstract: A gasket includes a flexible packing portion having a recess attached to a coupler of a plunger rod, and a core member harder than the packing portion. The recess has an internal circumferential surface with an internally threaded portion capable of being screwed on and thus engaging with an externally threaded portion provided on an external circumferential surface of the coupler. The core member has a helical shape defining the internal circumferential surface of the recess and the internally threaded portion provided on the internal circumferential surface. The packing portion defines a sliding surface brought into contact with an inner circumferential surface of a barrel, and the packing portion also covers an outer circumferential surface of the core member.

Abstract: An object of the present invention is to provide a nonhuman model animal of Th2-mediated hyperimmune response lacking PIR-B gene function on its chromosome by which the Th2-mediated immune response mechanism and allergy onset mechanism in vivo can be analyzed and which is liable to suffer from not only hyper-response of B cells but also allergy, and an inducer/promoter or an inhibitor for Th2-mediated immune response, etc. with the use of the nonhuman model animal of Th2-mediated hyperimmune response. The nonhuman model animal of Th2-mediated hyperimmune response is prepared by integrating a fragment comprising exons 1 to 7 and the domain in the 5? side of exon 8 of mouse PIR-B gene and another fragment containing exons 10 to 14 into a vector pMC1-Neo, cleaving it with Xho I-Sal I, integrating it into a vector pIC19R-MC1tk having herpes virus thymidine kinase to thereby construct targeting vector, transferring the targeting vector into ES cells and then injecting the ES cells into blastcyst.

Abstract: An object of the present invention is to provide a nonhuman model animal of Th2-mediated hyperimmune response lacking PIR-B gene function on its chromosome by which the Th2-mediated immune response mechanism and allergy onset mechanism in vivo can be analyzed and which is liable to suffer from not only hyper-response of B cells but also allergy, and an inducer/promoter or an inhibitor for Th2-mediated immune response, etc. with the use of the nonhuman model animal of Th2-mediated hyperimmune response. The nonhuman model animal of Th2-mediated hyperimmune response is prepared by integrating a fragment comprising exons 1 to 7 and the domain in the 5? side of exon 8 of mouse PIR-B gene and another fragment containing exons 10 to 14 into a vector pMC1-Neo, cleaving it with Xho I-Sal I, integrating it into a vector pIC19R-MC1tk having herpes virus thymidine kinase to thereby construct targeting vector, transferring the targeting vector into ES cells and then injecting the ES cells into blastcyst.

Abstract: The objects of the present invention is to provide a preventive method for the progress of neuropsychiatric disorders, a therapeutic agent for neuropsychiatric disorders, a screening method thereof, and a therapeutic method through the analysis of the mechanisms leading to neuropsychiatric disorders such as Nasu-Hakola diseases and the like. The non-human animal model of oligodendrocytes developmental disorders was generated by making the DAP12 gene function deficient on its chromosome. The DAP12 knockout mouse develops myelination disorders including hypomyelinosis in the brain, particularly in the frontal head and the thalamus, further leading to neuropsychiatric disorders such as Nasu-Hakola disease and the like with aging. The screening method for a therapeutic agent, the diagnostic method, and the therapeutic method, wherein the DAP12 knockout mouse developing these disorders are used, have been developed.

Abstract: The present invention intends to provide a non-human animal model of Guillain-Barré syndrome, which can be obtained by immunizing Fc?RIIB-gene-deficient non-human animal with ganglioside GQ1b, and a screening method of a therapeutic agent for Guillain-Barré syndrome using the non-human animal model. A mouse model of Guillain-Barré syndrome is generated by immunizing Fc?RIIB-gene-deficient mice with gangliosides GM1, GM2, GD1a, and GQ1b together with Freund's adjuvant every three weeks four times in total.

Abstract: An object of the present invention is to provide a nonhuman model animal of Th2-mediated hyperimmune response lacking PIR-B gene function on its chromosome by which the Th2-mediated immune response mechanism and allergy onset mechanism in vivo can be analyzed and which is liable to suffer from not only hyper-response of B cells but also allergy, and an inducer/promoter or an inhibitor for Th2-mediated immune response, etc. with the use of the nonhuman model animal of Th2-mediated hyperimmune response. The nonhuman model animal of Th2-mediated hyperimmune response is prepared by integrating a fragment comprising exons 1 to 7 and the domain in the 5? side of exon 8 of mouse PIR-B gene and another fragment containing exons 10 to 14 into a vector pMC1-Neo, cleaving it with Xho I-Sal I, integrating it into a vector pIC19R-MC1tk having herpes virus thymidine kinase to thereby construct targeting vector, transferring the targeting vector into ES cells and then injecting the ES cells into blastcyst.

Abstract: The present invention provides an experimental model animal which does not develop anaphylaxis, a type I allergy, can specifically induce Arthus reaction, a type III allergy, is not affected by type I allergy and evaluates type III allergy inflammation individually, and a method of screening a reaction accelerating or inhibitory substance in a type III allergy reaction through Fc?RIII by using said experimental model animal. In order to eliminate Fc?RIIB that demonstrates suppressive action to response through Fr?RIII, a mouse wherein the deletion mutation of both molecules of Lyn and Fc?RIIB are homozygotic (Lyn?IIB?) was generated by mating Lyn knockout mouse (Lyn?/?) and Fc?RIIB knockout mouse (Fc?RIIB?/?), and was used to measure and evaluate the deficiency of Fc?RIII function in systemic passive anaphylaxis and the reduction of Fc?RIII function in a bone marrow-derived mast cell, or the like.

Abstract: The present invention is to provide a non-human animal model of systemic lupus erythematosus wherein generation of anti-double stranded DNA antibody and anti-single stranded antibody is induced, and that is made to spontaneously develop glomerulonephritis and arthritis, and a screening method for a therapeutic agent for systemic lupus erythematosus wherein the non-human animal model is used. Fc?RIIB deficient mouse that is not made to spontaneously develop autoimmune pathology although its autoantibody response is enhanced is backcrossed into C57BL/6J (B6) mouse for 12 generations to generate Fc?RIIB deficient B6 mouse, the Fc?RIIB deficient B6 male mouse is intercrossed with lpr/B6 female mouse, and thus obtained Fc?RIIB+/?/lpr+/? mice were further crossed to generate a mouse model of systemic lupus erythematosus.

Abstract: The present invention provides a non-human model animal of Goodpasture's syndrome that contributes to the treatment of Goodpasture's syndrome where the development of therapy had been delayed due to the lack of adequate disease models, a method for screening a remedy for Goodpasture's syndrome by using the model animal, and a method for diagnosing Goodpasture's syndrome at the early stage. A Goodpasture's syndrome model mouse is constructed by immunizing immunoglobulin Fc? receptor IIB knockout mouse with type IV collagen, thereby inducing Goodpasture's syndrome. Moreover, a remedy for Goodpasture's syndrome is screened by administration of test substances to the Goodpasture's syndrome model mouse, followed by evaluating the severity of the expression of Goodpasture's syndrome as an index, such as diffuse alveolar hemorrhage, glomerulonephritis, the appearance of antikidney glomerular basement membrane antibody, and the like.

Abstract: The present invention intends to provide a non-human animal model of Guillain-Barré syndrome, which can be obtained by immunizing Fc?RIIB-gene-deficient non-human animal with ganglioside GQ1b, and a screening method of a therapeutic agent for Guillain-Barré syndrome using the non-human animal model. A mouse model of Guillain-Barré syndrome is generated by immunizing Fc?RIIB-gene-deficient mice with gangliosides GM1, GM2, GD1a, and GQ1b together with Freund's adjuvant every three weeks four times in total.

Abstract: The present invention provides a non-human model animal of Goodpasture's syndrome that contributes to the treatment of Goodpasture's syndrome where the development of therapy had been delayed due to the lack of adequate disease models, a method for screening a remedy for Goodpasture's syndrome by using the model animal, and a method for diagnosing Goodpasture's syndrome at the early stage. A Goodpasture's syndrome model mouse is constructed by immunizing immunoglobulin Fc? receptor IIB knockout mouse with type IV collagen, thereby inducing Goodpasture's syndrome. Moreover, a remedy for Goodpasture's syndrome is screened by administration of test substances to the Goodpasture's syndrome model mouse, followed by evaluating the severity of the expression of Goodpasture's syndrome as an index, such as diffuse alveolar hemorrhage, glomerulonephritis, the appearance of antikidney glomerular basement membrane antibody, and the like.

Abstract: The present invention provides a model animal with favorite onset of rheumatoid arthritis wherein the severity of arthritis reaches the maximum level and its onset ratio is a hundred percent, and a screening method of a remedy for rheumatoid arthritis by using the model animal. A mouse whose function of immunoglobulin Fc? receptor IIB gene is deficient on its chromosome and a wild-type collagen-induced arthritis-susceptible DBA/1J mouse are backcrossed six times or more, and a model mouse with favorite onset of rheumatoid arthritis is constructed. This model mouse with favorite onset of rheumatoid arthritis is immunized with bovine joint-origin type II collagen to develop collagen-induced arthritis.

Abstract: The present invention provides an immortalized natural killer cell line retaining the function and characteristics intrinsic to natural killer cells, a method for establishing the same, a method for screening for useful substances using the immortalized natural killer cell line, and a cell vaccine. By culturing natural killer cells obtained by isolating natural killer cells from the spleen of a transgenic mouse to which a large T-antigen gene of SV40 temperature-sensitive mutant tsA58 is introduced, a cell line which proliferates and activates in the presence of Interleukin-2, has azurophilic granules within cytoplasm, and retains an ability to kill a target cell without presensitization and/or an ability to kill target cells coated with an antibody, is established.

Abstract: The objects of the present invention is to provide a preventive method for the progress of neuropsychiatric disorders, a therapeutic agent for neuropsychiatric disorders, a screening method thereof, and a therapeutic method through the analysis of the mechanisms leading to neuropsychiatric disorders such as Nasu-Hakola diseases and the like. The non-human animal model of oligodendrocytes developmental disorders was generated by making the DAP12 gene function deficient on its chromosome. The DAP12 knockout mouse develops myelination disorders including hypomyelinosis in the brain, particularly in the frontal head and the thalamus, further leading to neuropsychiatric disorders such as Nasu-Hakola disease and the like with aging.

Abstract: An object of the present invention is to provide a nonhuman model animal of Th2-mediated hyperimmune response lacking PIR-B gene function on its chromosome by which the Th2-mediated immune response mechanism and allergy onset mechanism in vivo can be analyzed and which is liable to suffer from not only hyper-response of B cells but also allergy, and an inducer/promoter or an inhibitor for Th2-mediated immune response, etc. with the use of the nonhuman model animal of Th2-mediated hyperimmune response. The nonhuman model animal of Th2-mediated hyperimmune response is prepared by integrating a fragment comprising exons 1 to 7 and the domain in the 5? side of exon 8 of mouse PIR-B gene and another fragment containing exons 10 to 14 into a vector pMC1-Neo, cleaving it with Xho I-Sal I, integrating it into a vector pIC19R-MC1tk having herpes virus thymidine kinase to thereby construct targeting vector, transferring the targeting vector into ES cells and then injecting the ES cells into blastcyst.

Abstract: The present invention is to provide a non-human animal model of systemic lupus erythematosus wherein generation of anti-double stranded DNA antibody and anti-single stranded antibody is induced, and that is made to spontaneously develop glomerulonephritis and arthritis, and a screening method for a therapeutic agent for systemic lupus erythematosus wherein the non-human animal model is used. Fc?RIIB deficient mouse that is not made to spontaneously develop autoimmune pathology although its autoantibody response is enhanced is backcrossed into C57BL/6J (B6) mouse for 12 generations to generate Fc?RIIB deficient B6 mouse, the Fc?RIIB deficient B6 male mouse is intercrossed with lpr/B6 female mouse, and thus obtained Fc?RIIB+/?/lpr+/? mice were further crossed to generate a mouse model of systemic lupus erythematosus.

Abstract: The present invention provides an experimental model animal which does not develop anaphylaxis, a type I allergy, can specifically induce Arthus reaction, a type III allergy, is not affected by type I allergy and evaluates type III allergy inflammation individually, and a method of screening a reaction accelerating or inhibitory substance in a type III allergy reaction through Fc&ggr;RIII by using said experimental model animal. In order to eliminate Fc&ggr;RIIB that demonstrates suppressive action to response through Fr&ggr;RIII, a mouse wherein the deletion mutation of both molecules of Lyn and Fc&ggr;RIIB are homozygotic (Lyn−IIB−) was generated by mating Lyn knockout mouse (Lyn−/−) and Fc&ggr;RIIB knockout mouse (Fc&ggr;RIIB−/−), and was used to measure and evaluate the deficiency of Fc&ggr;RIII function in systemic passive anaphylaxis and the reduction of Fc&ggr;RIII function in a bone marrow-derived mast cell, or the like.

Abstract: The self-propelled stairs moving unit A1 moves on stairs, putting a manual wheelchair K on the pallet 7, by driving the front crawler traveling units 1a, 1b and the rear crawler traveling units 2a, 2b wherein right and left are unitedly connected with each other. When the stairs moving unit A1 is started to go up to the stairs from the flat face of lower hand, the front crawler traveling unit 1a relatively gently goes up. Then, the angle between the pallet 7 to be held to be level with the connecting shaft 6 which is rotation center of the traveling unit 1a as its center of oscillation and the line connecting both connecting portions of the support frames 5a connecting the front and rear crawler traveling units 1a, 2a (that is, the self-propelled portion) is slowly changed.