Abstract: One purpose of the present invention aims to provide a novel drug delivery means for targeting neovascularity. Another purpose of the invention is to provide a novel drug delivery means for targeting hyperpermeable vasculature. Still another purpose of the invention is to provide a method and a detection reagent for treatment or diagnosis of various diseases including malignant tumors. The present conjugate of a drug and an anti-HMGB1 antibody or an antigen-binding fragment thereof is administered to a subject and incorporated into proangiogenic or hyperpermeable vascular endothelial cells to deliver the drug to the cells. In addition, the conjugate is used to provide a method and a detection reagent for treatment or diagnosis of various diseases including malignant tumors.

Abstract: Provided is a more effective anti-inflammatory agent having less side effects as compared to NSAIDs and steroidal anti-inflammatory agents. A therapeutic agent for inflammatory diseases containing as an active ingredient an anti-4-HNE antibody, which inhibits 4-HNE, has been found to have ameliorating effects on the expressions of various inflammation markers involved in cerebral infarction and cerebral ischemia-reperfusion, and has also been found to have life-prolonging and life-saving effects in sepsis model animals. The anti-4-HNE antibody shows remarkable efficacy even on inflammatory diseases on which existing anti-inflammatory drugs, such as NSAIDs and steroidal anti-inflammatory agents, have hitherto not shown effects.

Abstract: It is an object of the present invention to provide an agent for enhancing phagocytosis ability, specifically an agent for enhancing phagocytosis ability that functions as a therapeutic agent or therapeutic adjunct for various bacterial infectious diseases, viral infectious diseases, fungal infectious diseases, parasitic infectious diseases, and mixed infectious diseases thereof by enhancing phagocytosis ability of neutrophils. The above-mentioned object is achieved by an agent for enhancing phagocytosis ability including HRG as an active ingredient. The inventors of the present invention have focused attention on the function of HRG on regulation of neutrophil activities, and as the result of extensive investigations, have newly found that HRG effectively enhances phagocytosis ability against a pathogen or foreign matter derived from bacteria, viruses, fungi, parasites, and the like among the neutrophil activities.

Abstract: The present invention provides a production inhibitor and/or scavenging promoter for reactive oxygen, and relates to a production inhibitor and/or scavenging promoter for reactive oxygen containing as an active ingredient a peptide having histidine-rich sequence. The histidine-rich sequence is the amino acid sequence identified by any one or a plurality of the following SEQ ID NOs: 2 to 8; (SEQ ID NO: 2) DLHPH; (SEQ ID NO: 3) KHHSH; (SEQ ID NO: 4) EQHPH; (SEQ ID NO: 5) GHHPH; (SEQ ID NO: 6) AHHPH; (SEQ ID NO: 7) EHDTH; and (SEQ ID NO: 8) RQHPH.

Abstract: Provided is a gene expression cassette for stably and highly producing a protein of interest. The gene expression cassette has a structure in which a DNA construct (X) containing a gene of interest and a poly A addition sequence is sandwiched between a promoter (P) and an enhancer (P?), the gene expression cassette further including transposon sequences (T) upstream of the promoter (P) and downstream of the enhancer (P?). Further, in the gene expression cassette, when a nuclear matrix binding sequence (M) is appropriately arranged upstream of a replication initiation sequence (S) in combination with the transposon sequence (T), the protein of interest can be more effectively produced stably and in a large amount. For example, HRG, PD-1, EMMPRIN, NPTN?, EMB, RAGE, MCAM, ALCAM, ErbB2, and an antibody can each be produced stably and in a large amount.

Abstract: The present invention provides a neutrophil activation regulator comprising a histidine-rich glycoprotein (HRG) for the treatment of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof. Further, the present invention provides methods for predicting the severity of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof, and methods for predicting the survival of a subject with systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation, that comprise determining the blood level of histidine-rich glycoprotein in the subject.

Abstract: The present invention provides a humanized anti-HMGB1 antibody which specifically binds to a sequence consisting of the C-terminal 8 amino acid residues (EEEDDDDE) of HMGB1 protein and is effective for treatment or prevention of various inflammatory diseases related to this protein, as well as an antigen-binding fragment thereof. The present invention also provides a pharmaceutical composition comprising such an antibody or antigen-binding fragment thereof.

Abstract: The present invention provides a therapeutic agent, a treatment method and an inspection method for diseases caused by activation of neutrophils. More specifically, the invention relates to a neutrophil activation regulator which comprising a histidine-rich glycoprotein (HRG) as an active ingredient, and provides a therapeutic agent for diseases caused by neutrophil activation comprising the neutrophil activation regulator, a treatment method for diseases caused by neutrophil activation, and further an inspection method for diseases caused by neutrophil activation. The present invention is based on the neutrophil activation regulator including the HRG as an active ingredient. The present invention extends to the depressant agent for neutrophil-vascular endothelial cell interaction including the HRG of the present invention as an active ingredient, the treatment method for diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation.

Abstract: The present invention provides a neutrophil activation regulator comprising a histidine-rich glycoprotein (HRG) for the treatment of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof. Further, the present invention provides methods for predicting the severity of systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation in a subject in need thereof, and methods for predicting the survival of a subject with systemic inflammatory response syndrome (SIRS), diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation, that comprise determining the blood level of histidine-rich glycoprotein in the subject.

Abstract: A character string selecting apparatus is provided with a menu display unit for setting a plurality of menu display areas, displaying, in a first column of the menu display area, selection target character strings extracted at intervals from selection target character strings provided with a display order, and displaying, in an i-th column, selection target character strings extracted at intervals smaller than intervals of extraction in an i-1-th column; a slide operation processing unit for scrolling display of selection target character strings of a j-th column in response to slide operation in the j-th column and display of the selection target character strings of the other columns in conjunction with each other based on amounts of scrolling according to the intervals of extraction; and a character string selection unit for specifying a selection target character string selected in one of the columns as an input character string.

Abstract: The present invention provides a therapeutic agent, a treatment method and an inspection method for diseases caused by activation of neutrophils. More specifically, the invention relates to a neutrophil activation regulator which comprising a histidine-rich glycoprotein (HRG) as an active ingredient, and provides a therapeutic agent for diseases caused by neutrophil activation comprising the neutrophil activation regulator, a treatment method for diseases caused by neutrophil activation, and further an inspection method for diseases caused by neutrophil activation. The present invention is based on the neutrophil activation regulator including the HRG as an active ingredient. The present invention extends to the depressant agent for neutrophil-vascular endothelial cell interaction including the HRG of the present invention as an active ingredient, the treatment method for diseases caused by neutrophil activation and/or inflammatory diseases accompanied by neutrophil activation.

Abstract: The objective of the present invention is to provide an agent which is useful for suppressing actual atherosclerosis and has few side-effects. The suppressant for atherosclerosis according to the present invention is characterized in comprising an anti-HMGB1 monoclonal antibody binding to C-tail of HMGB1 as an active component.

Abstract: An objective of the present invention is to provide a cerebral vasospasm inhibitor which is effective on cerebral vasospasm occurring after subarachnoid hemorrhage and has few side-effects. The cerebral vasospasm inhibitor of the invention is characterized in containing an anti-HMGB1 monoclonal antibody as an active ingredient.

Abstract: The objective to be solved by the present invention is to provide a method for effectively suppressing cerebral edema. The method for suppressing cerebral edema according to the present invention is characterized in comprising a step of administering an anti-HMGB 1 antibody recognizing 208EEEDDDDE215 (SEQ ID NO:1) as an HMGB1 epitope.

Abstract: An objective of the present invention is to provide a suppressant for cerebral infarction occurred after long-term ischemia associated with actual cerebral infarction, and has fewer side effects. The cerebral infarction suppressant of the present invention is characterized in comprising an anti-HMGB1 monoclonal antibody as an active ingredient.

Abstract: An objective of the present invention is to provide a cerebral vasospasm inhibitor which is effective on cerebral vasospasm occurring after subarachnoid hemorrhage and has few side-effects. The cerebral vasospasm inhibitor of the invention is characterized in containing an anti-HMGB1 monoclonal antibody as an active ingredient.

Abstract: An object of the present invention is to provide a cerebral infarction suppressant which is effective for brain tissue necrosis attributed to long-time ischemia as in actual cerebral infarction and has fewer side effects. The suppressant for cerebral infarction attributed to long-time ischemia according to the present invention is characterized in that a histidine and an H3-receptor blocker or a histidine and a histamine N-methyltransferase inhibitor are comprised as active ingredients.

Abstract: The present invention provides an input processing system which enables input of Chinese characters by kana-kanji conversion (Japanese syllable-Chinese character) or English words, etc. promptly with easy operation. All candidates of characters for input objects are set to a predetermined order and grouped into plural hierarchies, and are stored in a dictionary where a higher hierarchy group consists of each of the top item for one level lower hierarchy. According to an input position defined by an input unit, the lower hierarchy menu is displayed which is selected in the menu item in one level upper menu. The selected character is executed as an input object by pointing the menu item in the hierarchial menu.

Abstract: The present invention provides a small sized, inexpensive input unit which enables easy operation of computers, etc., even for people who have handicaps such as in the hands and/or fingers. The input unit consists of an input mode management part which manages input modes in correspondence with plural display-figures of the cursor; and when a button input detection part detects a turning ON or OFF of a button pressing signal produced by a button input unit, either changing the input modes by an input mode switching part or executing a cursor shift process according to the present input mode (ex. movement of cursor) by an input processing part is carried out depending on whether each time length of the button pressing signal is longer or shorter than the predetermined time length.