公开(公告)号：WO03070265A2

公开(公告)日：2003-08-28

申请号：PCT/NL0300127

申请日：2003-02-20

Applicant: AZ UNIV AMSTERDAM ,  VAN DEN BRINK GIJS ROBERT ,  PEPPELENBOSCH MAIKEL PETRUS ,  HARDWICK JAMES CHRISTOPHER HEN ,  VAN DEVENTER SANDER JAN HENDRI

Inventor： VAN DEN BRINK GIJS ROBERT ,  PEPPELENBOSCH MAIKEL PETRUS ,  HARDWICK JAMES CHRISTOPHER HEN ,  VAN DEVENTER SANDER JAN HENDRI

IPC: A61K38/00 ,  A61K38/17 ,  A61P35/00 ,  C12N1/21 ,  C12Q1/68 ,  G01N33/574 ,  G01N33/68

CPC classification number: G01N33/57446 ,  A61K38/1703 ,  C12Q1/6886 ,  C12Q2600/158

Abstract: The present invention is based on the key roles played by Hedgehog proteins in the regulation of homeostasis of the adult intestinal epithelium. Ihh is expressed in the adult mammalian colon and provides a lineage-instructive signal and regulates colonic epithelial morphogenesis in a compartmental fashion. Loss of Ihh expression precedes morphological change in colon tumorigenesis, i.e. carcinogenesis, and Ihh was absent in HT-29 colon carcinoma cells. Treatment of cancerous HT-29 cells with exogenous Hedgehog protein restored their differentiation. Ihh thus plays a pivotal role in the maintenance of colonic epithelial homeostasis in the differentiation of the GI tract cells and is essential for the enrolment of these GI tract cells on the Death program thus maintaining homeostasis to avoid or treat carcinogenesis. In addition, in gastric cancer expression of Shh is lost and loss of Shh expression precedes morphological changes in the parietal cells of the stomach. Shh is specifically expressed in fundic glands as well as in gastric heterotopia in the esophagus in Meckel's diverticulum. Shh thus has a unique role as a morphogen in fundic gland homeostasis. The present invention relates to methods in which a source of Hedgehog proteins is used prophylactically or therapeutically to maintain homeostasis of the adult intestinal epithelium. In particular the invention relates methods whereby sources of Hedgehog protein are used to prevent or treat carcinogenesis in adult gastric and colonic tissues. The invention also relates to Hedgehog-based method of diagnosing susceptibility for or the presence of carcinogenesis in the adult GI tract, particularly in gastric and colonic tissues. The invention further provide for compositions to be used in the Hedgehog-based methods of diagnosing, preventing and treating epithelial tumorigenesis in the adult GI tract.

Abstract translation: 本发明是基于Hedgehog蛋白质在调节成年肠上皮细胞稳态的关键作用。 Ihh在成年哺乳动物结肠中表达，并提供谱系指导信号并以分隔方式调节结肠上皮形态发生。 Ihh表达的丧失先于结肠肿瘤发生的形态学变化，即致癌作用，而在HT-29结肠癌细胞中Ihh不存在。 用外源Hedgehog蛋白治疗癌细胞HT-29细胞恢复分化。 因此，在维持肠道细胞分化中的结肠上皮内环境稳定方面起着关键作用，对于这些胃肠道细胞在死亡程序中的入选是至关重要的，因此保持体内平衡以避免或治疗癌变。 此外，在胃癌中，Shh的表达丧失，Shh表达的丧失先于胃的壁细胞的形态学变化。 Shh特异性表达在基底腺以及Meckel憩室食道胃异位症中。 因此，Shh在基底腺体内稳态中具有独特的形态学作用。 本发明涉及用于预防性或治疗性地使用刺猬蛋白源维持成年肠上皮的体内平衡的方法。 特别地，本发明涉及使用刺猬蛋白来源来预防或治疗成人胃和结肠组织中的癌发生的方法。 本发明还涉及用于诊断成人胃肠道，特别是胃和结肠组织中致癌作用的易感性或存在的基于刺猬的方法。 本发明进一步提供了用于诊断，预防和治疗成人GI道上皮肿瘤发生的基于Hedgehog的方法中使用的组合物。

公开(公告)号：WO9712960A3

公开(公告)日：2001-12-20

申请号：PCT/NL9600389

申请日：1996-10-04

Applicant: AZ UNIV AMSTERDAM ,  FLENDRIG LEONARDUS MARCUS

Inventor： FLENDRIG LEONARDUS MARCUS

IPC: C12M1/36 ,  A61K35/12 ,  A61K35/407 ,  A61M1/34 ,  C12M1/40 ,  C12M3/00 ,  C12N5/00 ,  C12N5/06 ,  C12N5/08 ,  C12N5/10

CPC classification number: A61M1/3472 ,  A61M1/3489 ,  C12M21/08 ,  C12M23/06 ,  C12M23/24 ,  C12M25/02 ,  C12M25/10 ,  C12M25/14 ,  C12N5/0068 ,  C12N2533/30

Abstract: The invention relates to a solid support for use in cell cultivation in vitro, comprising a 3D-matrix material and hollow fibres being permeable to at least gaseous oxygen and/or gaseous carbon dioxide, a biological reactor for the cultivation and/or maintenance of living cells comprising said solid support, as well as a method for culturing and/or maintaining living cells, using said solid support and/or said biological reactor. The solid support, biological reactor and method are especially suited for culturing human or animal derived liver cells, for use in or as a bio-artificial liver. The invention further relates to such a bio-artificial liver, as well as a method for treating liver disorders using said bio-artificial liver.

Abstract translation: 本发明涉及用于体外细胞培养的固体支持物，其包含三维基质材料和至少可气体氧和/或气态二氧化碳的中空纤维，用于培养和/或维持生物的生物反应器 包含所述固体支持物的细胞，以及使用所述固体支持物和/或所述生物反应器培养和/或维持活细胞的方法。 固体支持物，生物反应器和方法特别适用于培养人或动物来源的肝细胞，用于或作为生物人造肝。 本发明还涉及这样的生物人造肝，以及使用所述生物人造肝治疗肝脏疾病的方法。

公开(公告)号：WO9935286A3

公开(公告)日：1999-09-16

申请号：PCT/EP9900150

申请日：1999-01-06

Applicant: AZ UNIV AMSTERDAM ,  KUIVENHOVEN JAN ALBERT ,  KASTELEIN JOHANNES JACOBUS PIE

Inventor： KUIVENHOVEN JAN ALBERT ,  KASTELEIN JOHANNES JACOBUS PIE

IPC: C12N15/09 ,  C12Q1/68

CPC classification number: C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156

Abstract: The present invention relates to an assay for testing the genetic predisposition to respond to lipid-lowering therapy in patients with coronary artery disease (CAD), comprising identifying the presence or absence of a TaqIB restriction site in intron 1 in both alleles of the cholesteryl ester transfer protein (CETP) gene by suitable molecular biological techniques; and correlating the presence of the restriction site on one or both alleles with a high or intermediate, susceptibility for lipid-lowering therapy. The invention further relates to a testkit for performing the assay and to a cholesterol ester transfer protein (CETP) gene marker for identifying individuals that may or may not be susceptible for lipid-lowering therapies.

Abstract translation: 本发明涉及用于测试对冠状动脉疾病（CAD）患者中的降脂治疗有反应的遗传倾向的测定法，所述测定法包括鉴定胆固醇酯两个等位基因内含子1中TaqIB限制性位点的存在或不存在 通过合适的分子生物学技术转移蛋白（CETP）基因; 并将一个或两个等位基因上的限制性位点的存在与降脂治疗的高或中等易感性相关联。 本发明进一步涉及用于进行测定的测试套件以及用于鉴定对降脂疗法可能敏感或可能不敏感的个体的胆固醇酯转移蛋白（CETP）基因标志物。

公开(公告)号：WO2012004352A3

公开(公告)日：2012-03-08

申请号：PCT/EP2011061531

申请日：2011-07-07

Applicant: STICHTING TECH WETENSCHAPP ,  UNIV AMSTERDAM ,  UNIV DELFT TECH ,  REEK JOOST NICOLAAS HENDRIK ,  COPPENS MARC-OLIVIER

Inventor： REEK JOOST NICOLAAS HENDRIK ,  COPPENS MARC-OLIVIER

IPC: C07F15/00 ,  B01J31/24 ,  C07C45/49 ,  C07F19/00

CPC classification number: C07F15/008 ,  C07B2200/11

Abstract: The invention pertains to a diphosphine-transition metal complex comprising a diphosphine-transition metal ligand that is covalently bonded to an insoluble mesoporous support having an average pore diameter of from 4.5 nm to 50 nm, characterized in that the ligand as attached to the support has the formula: wherein R is aryl, C1-C4 alkyl, aralkyl, alkylaryl; C1-C4 alkoxy, aralkoxy, or alkylaryloxy; P is a phosphorous atom; M is a transition metal; X is a bond, CH2, 0, S or NH2; Y is C or N; A is a linking moiety which is bonded to the mesoporous support; the ring formed by X, Y and the two aromatic rings is a 5- or 6-membered ring; and wherein the aromatic rings may be unsubstituted or substituted. The invention further relates to the use of the diphosphine- transition metal complex as a catalyst in a reaction selected from hydroformylation, hydrogenation, carbonylation or carbon-carbon coupling.

Abstract translation: 本发明涉及二膦过渡金属络合物，其包含与平均孔径为4.5nm至50nm的不溶介孔载体共价键合的二膦过渡金属配体，其特征在于，附着于载体上的配体具有 下式：其中R是芳基，C 1 -C 4烷基，芳烷基，烷基芳基; C 1 -C 4烷氧基，芳烷氧基或烷基芳氧基; P是磷原子; M是过渡金属; X是键，CH2，O，S或NH2; Y为C或N; A是与中孔载体结合的连接部分; 由X，Y和两个芳环形成的环是5-或6-元环; 并且其中所述芳环可以是未取代的或取代的。 本发明还涉及二膦过渡金属络合物在选自加氢甲酰化，氢化，羰基化或碳 - 碳偶联的反应中作为催化剂的用途。

公开(公告)号：WO2010005310A3

公开(公告)日：2010-04-15

申请号：PCT/NL2009050418

申请日：2009-07-10

Applicant: AZ UNIV AMSTERDAM ,  BAAS FRANK ,  FLUITER KEES

Inventor： BAAS FRANK ,  FLUITER KEES

IPC: A61K31/7088 ,  A61P25/00

CPC classification number: C12N15/113 ,  A61K31/136 ,  A61K31/7088 ,  A61K31/785 ,  A61K38/215 ,  A61K39/3955 ,  A61K39/39591 ,  A61K45/06 ,  A61K48/00 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  A61K2300/00

Abstract: Disclosed are antagonists designed to inhibit or block expression of a mammalian complement such as complement component 6 (C6). The invention has a wide range of uses including use in the preparation of a medicament for the enhancement of nerve regeneration following acute or chronic nerve damage in a mammal.Additional applications include use in the treatment of multiple sclerosis either alone or in combination with another drug.

Abstract translation: 公开的是旨在抑制或阻断哺乳动物补体如补体成分6（C6）的表达的拮抗剂​​。 本发明具有广泛的用途，包括用于制备用于增强哺乳动物急性或慢性神经损伤后神经再生的药物。其它应用包括单独使用或与另一种药物组合治疗多发性硬化症 。

公开(公告)号：WO9915548B1

公开(公告)日：1999-09-02

申请号：PCT/EP9806183

申请日：1998-09-25

Applicant: AZ UNIV AMSTERDAM ,  UNIV TWENTE ,  NL ORGANISATIE VOOR WETENSCHAP ,  KRIJGSVELD JEROEN ,  ZAAT SEBASTIANUS ANTONIUS JOHA ,  DANKERT JACOB ,  KUIJPERS ALMA JOHANNA ,  ENGBERS GERARDUS HENRICUS MARI ,  FEIJEN JAN

Inventor： KRIJGSVELD JEROEN ,  ZAAT SEBASTIANUS ANTONIUS JOHA ,  DANKERT JACOB ,  KUIJPERS ALMA JOHANNA ,  ENGBERS GERARDUS HENRICUS MARI ,  FEIJEN JAN

IPC: C12N15/09 ,  A61K38/00 ,  A61K38/19 ,  A61P9/00 ,  A61P31/04 ,  A61P31/10 ,  C07K14/52

CPC classification number: C07K14/521 ,  A61K38/00

Abstract: The present invention relates to isolated and recombinant antimicrobial peptides thrombocidin-1 (TC-1) and thrombocidin-2 (TC-2), or variants thereof, which comprise at least in part the sequence as shown in figure 1 indicated by the label TC-1 and TC-2, and have antimicrobial activity against gram-positive and gram-negative bacteria, for example Escherichia coli, Bacillus subtilis, Streptococcus sanguis, Streptococcus pneumoniae, Staphylococcus epidermis, and Staphylococcus aureus, and/or against fungi, for example Candida albicans, C. glabarata, Cryptococcus neoformans, Aspergillus flavus, A. fumigatus, and Pseudoallescheria spec.. The invention further relates to the use of said peptides, or variants thereof, for the preparation of a medicament for the treatment of bacterial or fungal infections, such as endocarditis, in human and animals and the use of said peptides, or variants thereof, in release systems for prevention of bacterial or fungal infections in human and animals.

Abstract translation: 本发明涉及分离的和重组的抗微生物肽血小板生成素-1（TC-1）和血栓形成素-2（TC-2）或其变体，其至少部分包含如图1所示的由标签TC -1和TC-2，并且对例如大肠杆菌，枯草芽孢杆菌，血链球菌，肺炎链球菌，表皮葡萄球菌和金黄色葡萄球菌，和/或抗真菌的革兰氏阳性菌和革兰氏阴性菌具有抗微生物活性 白色念珠菌，glabarata，新型隐球菌，黄曲霉菌，烟曲霉和假黄曲霉。本发明进一步涉及所述肽或其变体在制备用于治疗细菌或真菌的药物中的用途 人和动物中的感染如心内膜炎以及所述肽或其变体在释放系统中用于预防人和动物中的细菌或真菌感染的用途。

公开(公告)号：WO9915548A3

公开(公告)日：1999-06-17

申请号：PCT/EP9806183

申请日：1998-09-25

Applicant: AZ UNIV AMSTERDAM ,  UNIV TWENTE ,  NL ORGANISATIE VOOR WETENSCHAP ,  KRIJGSVELD JEROEN ,  ZAAT SEBASTIANUS ANTONIUS JOHA ,  DANKERT JACOB ,  KUIJPERS ALMA JOHANNA ,  ENGBERS GERARDUS HENRICUS MARI ,  FEIJEN JAN

Inventor： KRIJGSVELD JEROEN ,  ZAAT SEBASTIANUS ANTONIUS JOHA ,  DANKERT JACOB ,  KUIJPERS ALMA JOHANNA ,  ENGBERS GERARDUS HENRICUS MARI ,  FEIJEN JAN

IPC: C12N15/09 ,  A61K38/00 ,  A61K38/19 ,  A61P9/00 ,  A61P31/04 ,  A61P31/10 ,  C07K14/52

CPC classification number: C07K14/521 ,  A61K38/00

Abstract: The present invention relates to isolated and recombinant antimicrobial peptides thrombocidin-1 (TC-1) and thrombocidin-2 (TC-2), or variants thereof, which comprise at least in part the sequence as shown in figure 1 indicated by the label TC-1 and TC-2, and have antimicrobial activity against gram-positive and gram-negative bacteria, for example Escherichia coli, Bacillus subtilis, Streptococcus sanguis, Streptococcus pneumoniae, Staphylococcus epidermis, and Staphylococcus aureus, and/or against fungi, for example Candida albicans, C. glabarata, Cryptococcus neoformans, Aspergillus flavus, A. fumigatus, and Pseudoallescheria spec.. The invention further relates to the use of said peptides, or variants thereof, for the preparation of a medicament for the treatment of bacterial or fungal infections, such as endocarditis, in human and animals and the use of said peptides, or variants thereof, in release systems for prevention of bacterial or fungal infections in human and animals.

公开(公告)号：WO2011105902A3

公开(公告)日：2011-11-17

申请号：PCT/NL2011050132

申请日：2011-02-23

Applicant: AZ UNIV AMSTERDAM ,  FLUITER KEES ,  BAAS FRANK

Inventor： FLUITER KEES ,  BAAS FRANK

IPC: C12N15/113 ,  A61K31/7088 ,  A61K31/712 ,  A61P37/06

CPC classification number: C12N15/113 ,  A61K31/7088 ,  A61K31/712 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/341

Abstract: Disclosed are antagonists designed to inhibit or block expression of a mammalian complement component 8-beta (C8-beta). The invention has a wide range of uses including use in the preparation of a medicament for the enhancement of nerve regeneration following acute or chronic nerve damage in a mammal.

Abstract translation: 公开了设计用于抑制或阻断哺乳动物补体成分8-β（C8-β）表达的拮抗剂​​。 本发明具有广泛的用途，包括用于制备用于增强哺乳动物急性或慢性神经损伤后神经再生的药物。

公开(公告)号：WO0133959A9

公开(公告)日：2006-08-17

申请号：PCT/NL0000814

申请日：2000-11-08

Applicant: UNIV AMSTERDAM ,  DOORSCHOT BENEDICT MARIE ,  JASPERS JORIS EMANUEL NICOLAAS

Inventor： DOORSCHOT BENEDICT MARIE ,  JASPERS JORIS EMANUEL NICOLAAS

IPC: A01N1/02 ,  F04B43/073

CPC classification number: F04B43/073 ,  A01N1/02 ,  A01N1/0247

Abstract: The invention relates to an apparatus for mechanical organ perfusion during the transport phase of a donor organ, which apparatus comprises an organ receptacle for acommodating the organ, propulsion means for moving the perfusate contained in a liquid compartment of the apparatus to and through the organ receptacle, and oxygenation means for the aeration of the organ receptacle. The propulsion means are embodied as a pump driven by compressed air, while the compressed air serves at the same time for the aeration of the organ receptacle.

Abstract translation: 本发明涉及一种用于在供体器官的输送阶段期间机械器官灌注的装置，该装置包括用于接收器官的器官容器，推进装置，用于将装置的液体隔室中的灌注液移动并穿过器官容器 ，以及用于器官容器通气的氧合装置。 推进装置被实施为由压缩空气驱动的泵，同时压缩空气同时用于器官容器的通气。

公开(公告)号：WO2005007890A3

公开(公告)日：2005-11-03

申请号：PCT/NL2004000520

申请日：2004-07-21

Applicant: AZ UNIV AMSTERDAM ,  LEIDS UNI MEDISCH CT ,  REITSMA PIETER HENDRIK ,  ROSENDAAL FRITS RICHARD

Inventor： REITSMA PIETER HENDRIK ,  ROSENDAAL FRITS RICHARD

IPC: C12Q1/68

CPC classification number: C12Q1/6883 ,  C12Q2600/156

Abstract: The invention provides a method for determining whether a subject is at risk of undergoing an infarction related to atherosclerosis comprising measuring an inflammation parameter in a sample obtained from said subject and determining whether the value of said inflammation parameter is indicative for said risk. Said sample preferably comprises a whole blood sample. More preferably, said inflammation parameter comprises an inflammation parameter of a cell and/or derivative thereof present in said sample, such as the amount of protein and/or RNA present upon and/or within such cells/derivatives. Additionally, an excreted product produced by said cell/derivative may be measured. The invention furthermore provides a method for quantifying at least one target nucleic acid in a sample, comprising incubating said sample with at least one probe capable of annealing to said target nucleic acid, amplifying annealed probes and quantifying said probes, characterized in that said sample comprises a whole blood sample.

Abstract translation: 本发明提供了用于确定受试者是否有经历与动脉粥样硬化相关的梗塞的风险的方法，包括测量从所述受试者获得的样品中的炎症参数并且确定所述炎症参数的值是否指示所述风险。 所述样品优选包含全血样品。 更优选地，所述炎症参数包括存在于所述样品中的细胞和/或其衍生物的炎症参数，例如存在于所述细胞/衍生物上和/或内的蛋白质和/或RNA的量。 此外，可以测量由所述细胞/衍生物产生的排泄物。 本发明还提供了用于定量样品中至少一种靶核酸的方法，包括将所述样品与能够与所述靶核酸退火的至少一种探针孵育，扩增退火的探针并定量所述探针，其特征在于所述样品包含 全血样本。