公开(公告)号：US20100003245A1

公开(公告)日：2010-01-07

申请号：US12374473

申请日：2007-07-19

申请人： Toshio Doi ,  Hideharu Abe ,  Naoshi Fukushima ,  Hitoshi Tai ,  Takakazu Mizuno ,  Masahiko Kinosaki

发明人： Toshio Doi ,  Hideharu Abe ,  Naoshi Fukushima ,  Hitoshi Tai ,  Takakazu Mizuno ,  Masahiko Kinosaki

IPC分类号： A61K39/395 ,  C12N5/06 ,  C07K16/18

CPC分类号： C07K16/22 ,  A61K2039/505 ,  C07K2317/76

摘要： When an anti-human BMP antibody was added to cells of an immortalized human mesangial cell line cultured in the presence of human BMP, the anti-human BMP antibody significantly suppressed the production of type IV collagen in mesangial cells. A number of signaling pathways are involved in abnormal proliferation of type IV collagen. It was therefore completely unpredictable whether merely blocking the BMP signal would indeed suppress the abnormal proliferation of type IV collagen. However, for the first time, the present inventors demonstrated that anti-BMP antibodies are very effective in suppressing the abnormal proliferation of type IV collagen. Thus, anti-BMP antibodies can be used as novel therapeutic agents for kidney diseases associated with abnormal proliferation of the mesangial matrix.

摘要翻译： 当将抗人BMP抗体加入到在人BMP存在下培养的永生化人肾小球系膜细胞的细胞中时，抗人BMP抗体显着抑制肾小球系膜细胞中IV型胶原的产生。 许多信号通路涉及IV型胶原异常增殖。 因此，完全不可预测的是，只是阻断BMP信号将确实抑制IV型胶原蛋白的异常增殖。 然而，本发明人第一次证明抗BMP抗体在抑制IV型胶原蛋白的异常增殖方面非常有效。 因此，抗BMP抗体可用作与肾小球系膜基质异常增殖相关的肾脏疾病的新型治疗剂。

公开(公告)号：US20100135988A1

公开(公告)日：2010-06-03

申请号：US12585882

申请日：2009-09-28

申请人： Toshio Doi ,  Hideharu Abe

发明人： Toshio Doi ,  Hideharu Abe

IPC分类号： A61K39/395 ,  C12Q1/00 ,  C12Q1/68 ,  G01N33/53 ,  C12Q1/48 ,  G01N33/561 ,  A61K31/7088

CPC分类号： C12Q1/6883 ,  A61K45/06 ,  C07K16/2863 ,  C07K2317/76 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/6893 ,  G01N2333/4703 ,  G01N2333/4706 ,  G01N2333/51 ,  G01N2333/71

摘要： A method of detecting proliferative diseases causing sclerosis, comprising measuring the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1, phosphorylated Smad1, activin receptor-like kinase 1, activin receptor-like kinase 3 and bone morphogenetic proteins in a biological sample. A kit therefor. A prophylactic and/or therapeutic agent for proliferative diseases causing sclerosis, comprising as an active ingredient a substance having an inhibitory effect on the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A method of identifying substances effective in preventing and/or treating proliferative diseases causing sclerosis, comprising judging whether or not a test substance inhibits the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A kit therefor.

摘要翻译： 一种检测引起硬化的增殖性疾病的方法，包括测量选自STAT3，磷酸化STAT3，Smad1，磷酸化Smad1，激活素受体样激酶1，激活素受体样激酶3和骨形态发生的至少一种物质的表达 生物样品中的蛋白质。 一个套件。 一种引起硬化的增殖性疾病的预防和/或治疗剂，其包含作为活性成分的对STAT3，磷酸化STAT3，Smad1和磷酸化Smad1中选择的至少一种物质的表达具有抑制作用的物质。 鉴定有效预防和/或治疗引起硬化的增殖性疾病的物质的方法，包括判断测试物质是否抑制至少一种选自STAT3，磷酸化STAT3，Smad1和磷酸化Smad1的物质的表达。 一个套件。

公开(公告)号：US08025881B2

公开(公告)日：2011-09-27

申请号：US12374473

申请日：2007-07-19

申请人： Toshio Doi ,  Hideharu Abe ,  Naoshi Fukushima ,  Hitoshi Tai ,  Takakazu Mizuno ,  Masahiko Kinosaki

发明人： Toshio Doi ,  Hideharu Abe ,  Naoshi Fukushima ,  Hitoshi Tai ,  Takakazu Mizuno ,  Masahiko Kinosaki

IPC分类号： A61K39/395 ,  C12N5/12 ,  C07K16/00 ,  C07K16/18 ,  C07K16/22

CPC分类号： C07K16/22 ,  A61K2039/505 ,  C07K2317/76

摘要： When an anti-human BMP antibody was added to cells of an immortalized human mesangial cell line cultured in the presence of human BMP, the anti-human BMP antibody significantly suppressed the production of type IV collagen in mesangial cells. A number of signaling pathways are involved in abnormal proliferation of type IV collagen. It was therefore completely unpredictable whether merely blocking the BMP signal would indeed suppress the abnormal proliferation of type IV collagen. However, for the first time, the present inventors demonstrated that anti-BMP antibodies are very effective in suppressing the abnormal proliferation of type IV collagen. Thus, anti-BMP antibodies can be used as novel therapeutic agents for kidney diseases associated with abnormal proliferation of the mesangial matrix.

摘要翻译： 当将抗人BMP抗体加入到在人BMP存在下培养的永生化人肾小球系膜细胞的细胞中时，抗人BMP抗体显着抑制肾小球系膜细胞中IV型胶原的产生。 许多信号通路涉及IV型胶原异常增殖。 因此，完全不可预测的是，只是阻断BMP信号将确实抑制IV型胶原蛋白的异常增殖。 然而，本发明人第一次证明抗BMP抗体在抑制IV型胶原蛋白的异常增殖方面非常有效。 因此，抗BMP抗体可用作与肾小球系膜基质异常增殖相关的肾脏疾病的新型治疗剂。

公开(公告)号：US07862993B2

公开(公告)日：2011-01-04

申请号：US10571511

申请日：2004-09-09

申请人： Toshio Doi ,  Hideharu Abe

发明人： Toshio Doi ,  Hideharu Abe

IPC分类号： G01N33/48 ,  G01N33/50 ,  G01N33/53 ,  G01N33/68

摘要： A method of detecting proliferative diseases causing sclerosis, comprising measuring the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1, phosphorylated Smad1, activin receptor-like kinase 1, activin receptor-like kinase 3 and bone morphogenetic proteins in a biological sample. A kit therefor. A prophylactic and/or therapeutic agent for proliferative diseases causing sclerosis, comprising as an active ingredient a substance having an inhibitory effect on the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A method of identifying substances effective in preventing and/or treating proliferative diseases causing sclerosis, comprising judging whether or not a test substance inhibits the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A kit therefor.

公开(公告)号：US09359645B2

公开(公告)日：2016-06-07

申请号：US12585882

申请日：2009-09-28

申请人： Toshio Doi ,  Hideharu Abe

发明人： Toshio Doi ,  Hideharu Abe

IPC分类号： A61K31/00 ,  A61K38/00 ,  A61K39/395 ,  G01N33/53 ,  C12Q1/68 ,  A61K45/06

CPC分类号： C12Q1/6883 ,  A61K45/06 ,  C07K16/2863 ,  C07K2317/76 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/6893 ,  G01N2333/4703 ,  G01N2333/4706 ,  G01N2333/51 ,  G01N2333/71

摘要： A method of detecting proliferative diseases causing sclerosis, comprising measuring the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1, phosphorylated Smad1, activin receptor-like kinase 1, activin receptor-like kinase 3 and bone morphogenetic proteins in a biological sample. A kit therefor. A prophylactic and/or therapeutic agent for proliferative diseases causing sclerosis, comprising as an active ingredient a substance having an inhibitory effect on the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A method of identifying substances effective in preventing and/or treating proliferative diseases causing sclerosis, comprising judging whether or not a test substance inhibits the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A kit therefor.

摘要翻译： 一种检测引起硬化的增殖性疾病的方法，包括测量选自STAT3，磷酸化STAT3，Smad1，磷酸化Smad1，激活素受体样激酶1，激活素受体样激酶3和骨形态发生的至少一种物质的表达 生物样品中的蛋白质。 一个套件。 一种引起硬化的增殖性疾病的预防和/或治疗剂，其包含作为活性成分的对STAT3，磷酸化STAT3，Smad1和磷酸化Smad1中选择的至少一种物质的表达具有抑制作用的物质。 鉴定有效预防和/或治疗引起硬化的增殖性疾病的物质的方法，包括判断测试物质是否抑制至少一种选自STAT3，磷酸化STAT3，Smad1和磷酸化Smad1的物质的表达。 一个套件。

公开(公告)号：US07901874B2

公开(公告)日：2011-03-08

申请号：US10571511

申请日：2004-09-09

申请人： Toshio Doi ,  Hideharu Abe

发明人： Toshio Doi ,  Hideharu Abe

IPC分类号： G01N33/48 ,  G01N33/50 ,  G01N33/53 ,  G01N33/68

CPC分类号： C12Q1/6883 ,  A61K45/06 ,  C07K16/2863 ,  C07K2317/76 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/6893 ,  G01N2333/4703 ,  G01N2333/4706 ,  G01N2333/51 ,  G01N2333/71

摘要： A method of detecting proliferative diseases causing sclerosis, comprising measuring the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1, phosphorylated Smad1, activin receptor-like kinase 1, activin receptor-like kinase 3 and bone morphogenetic proteins in a biological sample. A kit therefor. A prophylactic and/or therapeutic agent for proliferative diseases causing sclerosis, comprising as an active ingredient a substance having an inhibitory effect on the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A method of identifying substances effective in preventing and/or treating proliferative diseases causing sclerosis, comprising judging whether or not a test substance inhibits the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A kit therefor.

摘要翻译： 一种检测引起硬化的增殖性疾病的方法，包括测量选自STAT3，磷酸化STAT3，Smad1，磷酸化Smad1，激活素受体样激酶1，激活素受体样激酶3和骨形态发生的至少一种物质的表达 生物样品中的蛋白质。 一个套件。 一种引起硬化的增殖性疾病的预防和/或治疗剂，其包含作为活性成分的对STAT3，磷酸化STAT3，Smad1和磷酸化Smad1中选择的至少一种物质的表达具有抑制作用的物质。 鉴定有效预防和/或治疗引起硬化的增殖性疾病的物质的方法，包括判断测试物质是否抑制至少一种选自STAT3，磷酸化STAT3，Smad1和磷酸化Smad1的物质的表达。 一个套件。

公开(公告)号：US20080025967A1

公开(公告)日：2008-01-31

申请号：US10571511

申请日：2004-09-09

申请人： Toshio Doi ,  Hideharu Abe

发明人： Toshio Doi ,  Hideharu Abe

IPC分类号： A61K39/395 ,  A61K48/00 ,  A61P43/00 ,  C12Q1/48 ,  G01N33/53

CPC分类号： C12Q1/6883 ,  A61K45/06 ,  C07K16/2863 ,  C07K2317/76 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/6893 ,  G01N2333/4703 ,  G01N2333/4706 ,  G01N2333/51 ,  G01N2333/71

摘要： A method of detecting proliferative diseases causing sclerosis, comprising measuring the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1, phosphorylated Smad1, activin receptor-like kinase 1, activin receptor-like kinase 3 and bone morphogenetic proteins in a biological sample. A kit therefor. A prophylactic and/or therapeutic agent for proliferative diseases causing sclerosis, comprising as an active ingredient a substance having an inhibitory effect on the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A method of identifying substances effective in preventing and/or treating proliferative diseases causing sclerosis, comprising judging whether or not a test substance inhibits the expression of at least one substance selected from the group consisting of STAT3, phosphorylated STAT3, Smad1 and phosphorylated Smad1. A kit therefor.

摘要翻译： 一种检测引起硬化的增殖性疾病的方法，包括测量选自STAT3，磷酸化STAT3，Smad1，磷酸化Smad1，激活素受体样激酶1，激活素受体样激酶3和骨形态发生的至少一种物质的表达 生物样品中的蛋白质。 一个套件。 一种引起硬化的增殖性疾病的预防和/或治疗剂，其包含作为活性成分的对STAT3，磷酸化STAT3，Smad1和磷酸化Smad1中选择的至少一种物质的表达具有抑制作用的物质。 鉴定有效预防和/或治疗引起硬化的增殖性疾病的物质的方法，包括判断测试物质是否抑制至少一种选自STAT3，磷酸化STAT3，Smad1和磷酸化Smad1的物质的表达。 一个套件。

公开(公告)号：US5956520A

公开(公告)日：1999-09-21

申请号：US710902

申请日：1996-09-24

申请人： Toshio Kishi ,  Toru Shimizu ,  Shunichi Iwata ,  Shigeo Mizugaki ,  Yuichi Nakao ,  Toshio Doi

发明人： Toshio Kishi ,  Toru Shimizu ,  Shunichi Iwata ,  Shigeo Mizugaki ,  Yuichi Nakao ,  Toshio Doi

IPC分类号： G06F9/30 ,  G06F11/22 ,  G06F11/28 ,  G06F12/08 ,  G06F13/42 ,  G06F15/78 ,  G06F13/00

CPC分类号： G06F13/4213

摘要： An external bus I/F section has a function in which, when a bus access is requested by an instruction execution section, high-order several bits of a logical address generated by a CPU are outputted from an output terminal to the outside of a chip, as a space identifier for indicating which of an integrated ROM space, an integrated RAM space, and the external space is accessed by a currently executed program. A part of an address generated by the CPU is used so that the space which is accessed by the currently executed program is known from the outside in real time without requiring an external hardware.

摘要翻译： 外部总线I / F部分具有这样的功能，其中当由指令执行部分请求总线访问时，由CPU产生的逻辑地址的高位数位从输出端子输出到芯片的外部 作为用于指示由当前执行的程序访问的集成ROM空间，集成RAM空间和外部空间中的哪一个的空间标识符。 使用由CPU生成的地址的一部分，使得当前执行的程序访问的空间从外部实时获知，而不需要外部硬件。

公开(公告)号：US5737589A

公开(公告)日：1998-04-07

申请号：US308346

申请日：1994-09-19

申请人： Toshio Doi ,  Takehisa Hayashi ,  Tetsuo Nakano

发明人： Toshio Doi ,  Takehisa Hayashi ,  Tetsuo Nakano

IPC分类号： G06F13/42 ,  G06F1/12 ,  H04J3/06 ,  H04L7/02 ,  G06F1/06

CPC分类号： H04L7/02

摘要： The timing of digital signal sampling at a receiver is continuously adjusted relative to a master clock used to initiate sending, by controlling a phase difference between the receiver sampling clock and the master clock in accordance with feedback of an error signal determined by detecting deviation of sampling clock timing from desired reference timing during both start-up operation and normal operation. Propagation delay scattering in the individual devices is compensated for by setting the sampling clock at a desired reference timing at start-up. Propagation delay scattering caused by fluctuation during device operation is compensated for by detecting the deviation of the sampling clock timing from reference timing based on received digital signals during normal operation and then continuously correcting the sampling clock timing on the basis of the detection result.

摘要翻译： 通过根据通过检测采样偏差确定的误差信号的反馈来控制接收机采样时钟和主时钟之间的相位差，相对于用于发起发送的主时钟，连续地调整接收机处的数字信号采样定时 在启动操作和正常操作期间，从期望的基准定时的时钟定时。 通过将采样时钟设置在启动时的所需参考时序来补偿各个器件中的传播延迟散射。 通过在正常工作期间根据接收到的数字信号检测采样时钟定时与参考定时的偏差，然后根据检测结果连续校正采样时钟定时来补偿在器件工作期间引起的传播延迟散射。

公开(公告)号：US5544340A

公开(公告)日：1996-08-06

申请号：US362755

申请日：1994-12-22

申请人： Toshio Doi ,  Takehisa Hayashi ,  Kenichi Ishibashi ,  Takeshi Takemoto

发明人： Toshio Doi ,  Takehisa Hayashi ,  Kenichi Ishibashi ,  Takeshi Takemoto

IPC分类号： G06F12/08

CPC分类号： G06F12/0886

摘要： A method of controlling a cache memory disposed between a CPU and a main memory, wherein pairs of data and an address to be written in the cache memory are stored into a buffer memory. A plurality of pairs of data and an address read from the buffer memory are processed to compare the address fields thereof. Based on results of the comparisons, there is determined a write control for writing the data in the cache memory which has been subdivided into a plurality of banks. As a result, the plural pairs of data and an address are written into the plural banks of the cache memory, the addresses of the respective pairs being different from each other. With the provisions set forth above, the write operation can be independently conducted for each bank of the cache memory, thereby improving the write throughput.

摘要翻译： 一种控制设置在CPU和主存储器之间的高速缓冲存储器的方法，其中将要写入高速缓冲存储器的数据和地址对存储在缓冲存储器中。 处理从缓冲存储器读取的多对数据和地址，以比较其地址字段。 基于比较的结果，确定了将数据写入高速缓冲存储器中的写入控制，其被细分为多个存储体。 结果，将多对数据和地址写入高速缓冲存储器的多个组，各对的地址彼此不同。 通过上述规定，可以对高速缓冲存储器的每一组独立地进行写入操作，从而提高写入吞吐量。