JP5094793B2 - 心血管疾患マーカーおよび治療標的としてのil1rl−1 - Google Patents
心血管疾患マーカーおよび治療標的としてのil1rl−1 Download PDFInfo
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- JP5094793B2 JP5094793B2 JP2009173539A JP2009173539A JP5094793B2 JP 5094793 B2 JP5094793 B2 JP 5094793B2 JP 2009173539 A JP2009173539 A JP 2009173539A JP 2009173539 A JP2009173539 A JP 2009173539A JP 5094793 B2 JP5094793 B2 JP 5094793B2
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Description
本発明は、心血管症状の診断および処置のための方法および組成物に関する。より具体的には、本発明は、心肥大、心筋梗塞、卒中、動脈硬化、および心不全を含む心血管症状の処置に用いることができる単離された分子に関する。
心血管疾患は、治療法の著しい進歩にかかわらず、相変わらず先進国での罹患率および死亡率の唯一最も一般的な病因のままである。したがって、心筋梗塞および卒中等の心血管症状の予防および治療は、公衆衛生上の大きな問題の一領域である。現在、将来の心血管疾患にかかわる危険因子(リスクファクタ)がいくつか記載されており、ハイリスクの被験体の検出に幅広く臨床的に使われている。このようなスクーリングテストとしては、全コレステロール値およびHDLコレステロール値の評価が挙げられる。しかし、リスクプロファイルが明らかに低程度から中程度である被験体で、数多くの心血管疾患が生じており、そのような患者を識別する能力には限界がある。さらに、蓄積されているデータによれば、異なる患者群間では、心血管疾患の危険性がある患者または心血管疾患を有すると知られている患者に対する一定の予防および治療上の処置の有益な効果の大きさが異なることが示唆される。しかし、この時点では、一定の治療が多かれ少なかれ有効であるか否かを判断する診断テストについて記述したデータが欠けている。
本発明は、心血管症状の診断および処置のための方法および組成物を提供する。より具体的には、心臓細胞が機械的に誘発された歪みを受けた場合にその細胞内で上方制御される遺伝子を同定した。これらの発見を鑑みて、心肥大、心筋梗塞、卒中、動脈硬化、および心不全等の心血管(血管含む)症状を処置するために本発明の分子が使用され得ると考えられる。
2が可溶型、配列番号3および4が膜型である)である。以下、明細書全体にわたってこれらの用語IL1RL−1、T1/ST2、ST2、およびFit−1は、相互変換可能に使用される)。いくつかの実施形態では、上記疾患は、心筋梗塞、卒中、動脈硬化、および心不全からなる群から選択される心血管症状である。一実施形態では、上記疾患は心臓肥大である。別の実施形態では、上記疾患は心不全である。いくつかの実施形態では、生物学的サンプルとしては、生検サンプルおよび体液(例:血液/血清)が挙げられる。
(項目1)
核酸分子の異常発現またはその発現産物によって特徴づけられる心血管症状を診断する方法であって、該方法は、以下:
a)該核酸分子、その発現産物、またはその発現産物のフラグメントに特異的に結合する薬剤を、被験体から得た生体試料と接触させる工程;および
b)結合した薬剤の量を測定し、そして該測定から該核酸分子の発現またはその発現産物の発現が異常であるか否かを決定して、異常発現が該症状を診断される工程、
を包含し、ここで、該核酸分子が、配列番号1および配列番号3からなる群から選択される少なくとも1つの核酸分子である、方法。
(項目2)
上記症状が、心筋梗塞、卒中、動脈硬化、および心不全からなる群から選択される心血管症状である、項目1に記載の方法。
(項目3)
上記症状が、心臓肥大である、項目1に記載の方法。
(項目4)
上記薬剤が、高ストリンジェントな条件下で上記配列番号1または配列番号3の核酸分子にハイブリダイズする核酸分子である、項目1に記載の方法。
(項目5)
上記薬剤が、上記配列番号1または配列番号3の核酸分子の上記発現産物に結合する分子である、項目1に記載の方法。
(項目6)
上記薬剤が抗体またはその抗原結合フラグメントである、項目5に記載の方法。
(項目7)
核酸分子の異常発現またはその発現産物によって特徴づけられる被験体での心血管症状の病期を決定する方法であって、
患者から得た試料を、
(i)IL1RL−1核酸分子、
(ii)該IL1RL−1核酸にコードされるポリペプチド、
(iii)該ポリペプチドに由来するペプチド、および
(iv)該ポリペプチドまたはペプチドに選択的に結合する抗体
からなる群から選択されるパラメータについて、該被験体での該心血管症状の病期の決定としてモニタリングする工程を包含する、方法。
(項目8)
上記試料が体液または組織である、項目7に記載の方法。
(項目9)
上記モニタリング工程が、
(a)ストリンジェントな条件下で上記(i)の核酸分子に選択的にハイブリダイズする単離された核酸分子、
(b)上記(ii)のポリペプチドまたは上記(iii)のペプチドに選択的に結合する抗体、および
(c)上記(iv)の抗体に選択的に結合するポリペプチドまたはペプチド
からなる群から選択される検出可能な薬剤と上記試料を接触させる工程を包含する、項目7に記載の方法。
(項目10)
上記抗体、上記ポリペプチド、上記ペプチド、または上記核酸が検出可能な標識で標識される、項目9に記載の方法。
(項目11)
上記ペプチドについて上記試料をモニタリングする工程を包含する、項目9に記載の方法。
(項目12)
単離IL1RL−1核酸分子またはその発現産物に選択的に結合する薬剤と、該単離核酸またはその発現産物への該薬剤の結合の測定値と比較するための対照とを含有するパッケージを含む、キット。
(項目13)
上記対照が、上記測定値と比較するための所定の値を有する、項目12に記載のキット。
(項目14)
上記対照が、単離IL1RL−1核酸分子の上記発現産物のエピトープを含む、項目12に記載のキット。
(項目15)
上記薬剤が、上記単離IL1RL−1核酸分子を増幅するための少なくとも1つのプライマー対を含み、該単離IL1RL−1核酸分子が配列番号1または配列番号3として示される配列を有する、項目12に記載のキット。
(項目16)
上記薬剤が、上記単離IL1RL−1核酸分子の上記発現産物に結合する少なくとも1つの抗体を含み、上記単離IL1RL−1核酸分子が配列番号1または配列番号3として示される配列を有する、項目12に記載のキット。
(項目17)
心血管症状を処置する方法であって、
そのような処置を必要とする被験体に対して、該心血管症状を処置するのに有効な量で、IL1RL−1分子の発現を調節する薬剤を投与する工程を包含する、方法。
(項目18)
抗炎症薬剤、抗血栓症薬剤、抗血小板薬剤、線維素溶解薬剤、脂質還元薬剤、直接トロンビンインヒビター、糖蛋白IIb/IIIaレセプターインヒビター、細胞接着分子に結合して白血球がそのような分子に結合する能力を阻害する薬剤、カルシウムチャンネルブロッカー、βアドレナリン作動性レセプターブロッカー、サイクロオキシゲナーゼ2インヒビター、およびアンギオテンシン系インヒビターからなる群から選択される薬剤を共投与する工程をさらに包含する、項目17に記載の方法。
(項目19)
上記心血管症状が、心肥大、心筋梗塞、卒中、動脈硬化、および心不全からなる群から選択される、項目17に記載の方法。
(項目20)
上記発現を調節する薬剤が、IL1RL−1分子である、項目17に記載の方法。
(項目21)
被験体での心血管症状発症の危険性を減少させるために該被験体を処置する方法であって、
増加量IL1RL−1分子を発現する被験体に対して、該被験体が将来に心血管障害を発症する危険性を減少させるのに有効な量で心血管障害患の危険性を減少させるための薬剤を投与する工程を包含し、
上記薬剤が抗炎症薬剤、抗血栓症薬剤、抗血小板薬剤、線維素溶解薬剤、脂質還元薬剤、直接トロンビンインヒビター、糖蛋白IIb/IIIaレセプターインヒビター、細胞接着分子に結合して白血球がそのような分子に結合する能力を阻害する薬剤、カルシウムチャンネルブロッカー、βアドレナリン作動性レセプターブロッカー、サイクロオキシゲナーゼ2インヒビター、またはアンギオテンシン系インヒビター、あるいはIL1RL−1分子の発現を調節する薬剤である、方法。
(項目22)
心血管症状の処置に有用な候補薬剤を同定する方法であって、
候補薬剤の不在下でIL1RL−1核酸分子の第1の発現量を可能とする条件下で、心筋細胞または心筋組織のIL1RL−1核酸分子の発現を測定する工程、
該心筋細胞または心筋組織を上記候補薬剤と接触させる工程、および
該IL1RL−1核酸分子の試験発現量を検出する工程を包含し、
該候補薬剤の存在下での該第1の発現量に対する該試験発現量の増加または減少が、該候補薬剤が該心血管症状の処置に有用であることを示す、方法。
(項目23)
上記心血管症状が、心肥大、心筋梗塞、卒中、動脈硬化、および心不全からなる群から選択される、項目22に記載の方法。
(項目24)
心血管症状を処置するための薬学的有効量の単離IL1RL−1核酸分子またはその発現産物を含む薬剤、および
薬学的に受容可能な担体、
を含有する、医薬組成物。
(項目25)
上記薬剤が、上記単離IL1RL−1核酸分子の発現産物である、項目24に記載の医薬組成物。
(項目26)
上記心血管症状が、心肥大、心筋梗塞、卒中、動脈硬化、および心不全からなる群から選択されることを特徴とする項目24に記載の医薬組成物。
(項目27)
心血管症状の危険度を減らすために、抗炎症薬剤、抗血栓症薬剤、抗血小板薬剤、線維素溶解薬剤、脂質還元薬剤、直接トロンビンインヒビター、糖蛋白IIb/IIIaレセプターインヒビター、細胞接着分子に結合して白血球がそのような分子に結合する能力を阻害する薬剤、カルシウムチャンネルブロッカー、βアドレナリン作動性レセプターブロッカー、サイクロオキシゲナーゼ2インヒビター、およびアンギオテンシン系インヒビターからなる群から選択される薬剤による処置によって被験体が利益を得る可能性を評価する方法であって、該方法は、以下:
該被験体体内のIL1RL−1分子濃度を得る工程、および
該IL1RL−1分子濃度と心血管症状の診断にとって特異的な所定の値とを比較する工程、
を包含し、ここで、該所定の値と比較した該IL1RL−1分子量は、上記被験体が上記薬剤による処置から利益を得るか否かを示す、方法。
(項目28)
上記心血管症状の診断に特異的な所定の値が、複数の所定マーカー濃度範囲であり、かつ上記比較工程が、上記被験体レベルがどの該所定マーカー濃度範囲内であるかを検定する工程を包含する、項目27に記載の方法。
(項目29)
上記心血管症状が、心肥大、心筋梗塞、卒中、動脈硬化、および心不全からなる群から選択されることを特徴とする項目27に記載の方法。
(項目30)
心血管症状の危険度を減少させるために被験体を処置する方法であって、異常値のIL1RL−1分子を発現する被験体に対して、該被検体が心血管症状を発症する危険度を減少させるのに有効な量で心血管症状の危険度を減少させるための薬剤を選択および投与する工程を包含し、該薬剤が、抗炎症薬剤、抗血栓症薬剤、抗血小板薬剤、線維素溶解薬剤、脂質還元薬剤、直接トロンビンインヒビター、糖蛋白IIb/IIIaレセプターインヒビター、細胞接着分子に結合して白血球がそのような分子に結合する能力を阻害する薬剤、カルシウムチャンネルブロッカー、βアドレナリン作動性レセプターブロッカー、サイクロオキシゲナーゼ2インヒビター、およびアンギオテンシン系インヒビターからなる群から選択される、方法。
(項目31)
上記被験体が、他の点では上記薬剤による処置を必要としている症状を有さない、項目30に記載の方法。
(項目32)
心血管症状の結果を予測する方法であって、該方法が、以下:
被験体内のIL1RL−1分子濃度を得る工程、および
該IL1RL−1分子濃度と該心血管症状の結果を予測するために特異的な所定の値とを比較する工程、
を包含し、ここで、該所定の値と比較した該IL1RL−1分子濃度が該心血管症状の該結果を示す、方法。
(項目33)
上記心血管症状が、心肥大、心筋梗塞、卒中、動脈硬化、および心不全からなる群から選択される、項目32に記載の方法。
配列番号1は、ヒトIL1RL1(可溶性)cDNAのヌクレオチド配列である。
本発明は、機械的に誘導された歪み変形を心臓細胞が受ける場合、該心臓細胞で上方制御される多数の遺伝子の発見を含む。この発見の観点から、本発明の分子が心臓肥大、心筋梗塞、卒中、動脈硬化、および/または心不全を含む心血管症状の処置に用いられ得ると考えられている。
eハイドロパシー分析が公的なもの(EMBL、Heidelberg、Germany)および市販のもの(例えば、MacVector配列分析用ソフトウェア、Oxford Molecular Group/Genetics Computer Group,Madison,WI,Acceirys,Inc.,San Diego,CAから入手)を用いて得ることができる。前述核酸のワトソン−クリック相補体も、本発明によって包含される。
.1を持つ配列が本発明の相同のラット配列と置換可能に用いることができる。
ヌクレオチド1から始まりヌクレオチド1357で終わり、また配列番号3はヌクレオチド1から始まり、ヌクレオチド2058で終わり、またはその相補体、すなわち20以上のヌクレオチド長がユニークである。当業者は、既知のデータベース上の配列に対してこのフラグメントのヒトゲノム中の他の配列から目的とする配列を選択的に区別するユニークフラグメントの能力に概ね基づいて、そのような配列を選択する方法を熟知している。一般的には以上が必要なものではあるが、インビトロで確認的なハイブリダイゼーションおよび配列決定分析をおこなってもよい。
または「RNAi」の使用は、遺伝子発現を阻害するために二本鎖RNA(dsRNA)の使用を含む(例えばSui,G,ら,Proc Natl.Acad.Sci U.S.A.99:5515−5520,2002を参照)。本発明の実施形態でRNAi戦略を適用する方法は、当業者にわかるだろう。
ー、塩類、緩衝液、安定剤、可溶化剤、および他の材料を含む。
離することで、ポリペプチドを、組織または細胞ホモジュネートを含む生体試料から単離することができ、またこのようなポリペプチドを種々の原核細胞発現系および真核細胞発現系で組み換え発現させることもできる。抗原ペプチド(例えば、免疫認識のために細胞の表面でMHC分子によって表されるもの)等の短いポリペプチドもまた、十分に確立されたペプチド合成法を用いて化学合成することができる。
できる。DahiyatおよびMayoの計算方法を適用することで、前述のポリペプチドのいずれかの特定改変体を提案し、かつ試験することで、該改変体が所望の高次構造を保持するかどうかを判断する。
Harbor,New York,1989、またはCurrent Protocols in Molecular Biology,F.M.Ausubel,ら,eds.,John Wiley & Sons,Inc.,New York)。アミノ酸の保存的置換は、a)M,I,L,V;(b)F,Y,W;(c)K,R,H;(d)A,G;(e)S,T;(f)Q,N;および(g)E,Dからなる群の範囲内のアミノ酸間でおこなわれる置換を含む。
然変異誘発によって、またはポリペプチドをコードする遺伝子の化学合成によって、行うことが可能である。ポリペプチドの機能的に等価なフラグメントの活性は、変性ポリペプチドをコードする遺伝子を細菌またはほ乳類の発現ベクターにクローニングし、該ベクターを適当な宿主細胞に導入し、変性ポリペプチドを発現させ、さらに本明細書に記載したようにポリペプチドの機能的能力を試験することによって、試験することができる。
セイを介して実施することができる。
FRおよび/またはCDR1および/またはCDR2および/または軽鎖CDR3領域が相同ヒトまたは非ヒト配列によって置換されているキメラFabフラグメント抗体;FRおよび/またはCDR1および/またはCDR2および/または軽鎖CDR3領域が相同ヒトまたは非ヒト配列によって置換されているキメラFdフラグメント抗体も提供する。本発明は、いわゆる単一鎖抗体も含む。
または細胞外結合標的から構成される。天然ポリペプチド結合標的を用いる一方で、アッセイで測定可能なポリペプチドフラグメントに対して、部分または類似体が結合親和性および結合活性を与える限り、該ポリペプチド結合標的の部分(例えば、ペプチドまたは核酸フラグメント)あるいは類似体(すなわち、アッセイの目的のために天然結合標的のポリペプチド結合特性を模倣した薬剤)を用いることが好ましい。
離工程を、種々の方法で達成することが可能である。都合の良いことに、構成要素のうちの少なくとも1つは固体基板上で固定され、そこから未結合構成要素は容易が容易に分離可能である。固体基板を多種多様な材料かつ多種多様な形状(例えば、マイクロタイターのプレート、マイクロボード、計量棒、および樹脂粒子)で作ることができる。好ましくは、シグナル対ノイズ比を最大にするために基板を選択し、主にバックグラウンド結合を最小限にするとともに、分離を容易にし、かつコストを軽減する。
質結合アッセイ、イムノアッセイ等が挙げられる。本発明のポリペプチドに結合する薬剤のスクリーニングに有用な他のアッセイとして、蛍光共振エネルギー移動(FRET)および電気泳動度シフト分析(EMSA)が挙げられる。
た核酸のいずれかの発現産物のエピトープを含む。
expression)」としては、上記心血管症状の治療に有効な量の本明細書に記載したIL1RL−1分子のいずれか、それらの分子の発現を増加させる薬剤、同様に前述のIL1RL−1分子のいずれかの発現を減少させる薬剤が挙げられる。
導プロモーターは、誘導薬剤の存在下で活性化される。例えば、メタロチオネインプロモーターは、活性化されて、特定の金属イオンの存在下で転写および翻訳を増加させる。他の誘導プロモーターは、当業者に公知である。
列および本発明の核酸配列に結合しうる追加の核酸フラグメント(例えば、エンハンサーおよびプロモーター)を挿入または取り込ませることによって操作されたプラスミド、ファージミド、ウイルス、ウイルスもしくはバクテリア源由来のビヒクルが挙げられる。ウイルスベクターは、ベクターの好ましい型であり、限定されるものではないが、以下のウイルス由来の核酸配列が挙げられる。すなわち、アデノウイルス;アデノ随伴ウイルス;レトロウイルス(例えばマローニーマウス白血病ウイルス);ハービーマウス肉腫ウイルス;マウス乳癌ウイルス;ラウス肉腫ウイルス;SV40−型ウイルス;ポリオーマウイルス;エプスタイン−バーウイルス;乳頭腫ウイルス;ヘルペスウイルス;ワクシニアウイルス;ポリオウイルス;およびレトロウイルスのようなRNAウイルスが挙げられる。当業者は名付けられてはいないが当該分野で公知である他のベクターを容易に用いることができる。
ulligan他の米国特許第5,674,722号に記載されている。
ア(核酸が固形の重合マトリックス全体にわたって分散)またはマイクロカプセル(核酸が重合殻のコアに保存される)のような微粒子の形態である。本発明の核酸を含有するための重合マトリックスの別の形態としては、膜、コーティング、ゲル、インプラント、およびステントが挙げられる。重合マトリックスデバイスの大きさおよび組成は、マトリックスデバイスがインプラントされる組織における好ましい放出カイネティックをもたらすように、選択される。さらに、重合マトリックスデバイスの大きさは、使用する送達方法にもとづいて選択され、一般に組織への注射、またはエアゾルによる懸濁液の鼻および/または肺領域への投与である。重合マトリックス組成は、好ましい分解率を持つように、かつ生体粘着性(生粘着性)を持つ材料により形成され、デバイスが血管の表面に投与される場合、移動の効果がさらに高まるようにの両方で、選択される。上記マトリックスの組成もまた、分解しないように、しかしむしろ、長時間にわたり拡散によって放出するように、選択される。
、それらの化学的誘導体(置換、化学基の付加、例えば、アルキル、アルキレン、水酸化、酸化、ならびに当業者によって慣用的に作られた他の修飾)、アルブミンおよび他の親水性タンパク質、ゼインおよび他プロラミンおよび疎水性タンパク質、コポリマー、およびそれらの混合物が挙げられる。一般に、これらの材料は、表面またはバルクの浸食によって、酵素的加水分解またはインビボで水にさらすことで、分解する。
に対するリガンドに対して特異的な抗体のような分子は、核酸送達ビヒクルに結合または取り込まれ得る。例えば、リポソームが本発明の核酸を送達するために使用される場合、エンドサイトーシスに伴う表面膜タンパク質と結合するタンパク質は標的化のため、および/または取り込みを容易にするためにリポソーム剤形に組み込まれ得る。そのようなタンパク質として、特定の細胞型向性のカプシドタンパク質またはそのフラグメント、周期の際に内在化を受けるタンパク質に対する抗体、細胞内局在を標的として、細胞内半減期を強化するタンパク質などが挙げられる。重合送達系も、当業者に公知なように、細胞に核酸を成功裏に送達させるために使われている。そのような系は、核酸を経口投与することが可能である。
60mmHg)を下回ると、血管拡張は不適切となって脳血流量は減少する。しかし、脳は脳血流量の低下を補償することができるパーフュージョン予備を持っている。標準状態の下で血液によって送達される酸素の約35%だけが抽出されるので、この予備が存在する。したがって、その酸素正常状態と炭酸正常状態とが存在するならば、増加する酸素抽出を起こすことができる。遠位血圧がほぼ30mmHg以下に落ちると、2つの代償性メカニズム(自己調節とパーフュージョン予備)は酸素輸送の障害を予防するには不十分である。
る。本明細書で用いられるように、虚血性の卒中の異常に上がる危険度を持っている被験体は、従来の医療(以前の議論を参照せよ)によって決定されるカテゴリーである。そのような被験体は、また、危険因子が卒中であることを知っているか、脳血管イベントの危険度増加を持ちながら従来の医療で同定され得る。例えば、このカテゴリーは、選択的な血管手術を受けている被験体を含む。代表的に、心臓病に伴う危険因子は、卒中を伴う危険因子と同じである。一次性の危険因子として、緊張亢進、コレステロール過剰血、および喫煙が挙げられる。心房細動またはその最近の心筋梗塞もまた、重要な危険因子である。加えて、本発明によれば、IL1RL−1の核酸分子またはその発現産物の改変発現量もまた、重要な危険因子である。
である。
で本発明の薬剤を含む。
とができる。すなわち、コレステロール、コレステロールエステル、および脂肪酸または中性脂肪(モノグリセリド、ジグリセリド、およびトリグリセリド等)等のステロールを含む脂質、ヒドロゲル放出系、シラスチック系、ペプチドベース系、ワックスコーティング、従来の結合剤と賦形剤を用いた圧縮錠剤、部分的融合インプラント等である。特定の例としては、限定はされないが、以下:(a)本発明の薬剤が米国特許第4,452,775号、第4,675,189号、および第5,736,152号に記載されるもの等のマトリックス内の形態で含有される腐食系、および(b)活性成分が米国特許第3,854,480号、第5,133,974号、および第5,407,686号に記載されるもの等の高分子からの制御された速度で浸透する拡散系とが挙げられる。さらに、ポンプベース金物類送達系を用いることができ、そのいくつかは、移植に適応される。
e、Fentiazac、Flazalone、Fluazacort、Flufenamic Acid、Flumizole、Flunisolide Acetate、Flunixin、Flunixin Meglumine、Fluocortin Butyl、Fluorometholone Acetate、Fluquazone、Flurbiprofen、Fluretofen、Fluticasone Propionate、Furaprofen、Furobufen、Halcinonide、Halobetasol Propionate、Halopredone Acetate、Ibufenac、Ibuprofen、Ibuprofen Aluminum、Ibuprofen Piconol、Ilonidap、Indomethacin、Indomethacin Sodium、Indoprofen、Indoxole、Intrazole、Isoflupredone Acetate、Isoxepac、Isoxicam、Ketoprofen、Lofemizole Hydrochloride、Lornoxicam;Loteprednol Etabonate、Meclofenamate Sodium、Meclofenamic Acid、Meclorisone Dibutyrate、Mefenamic Acid、Mesalamine、Meseclazone、Methylprednisolone Suleptanate、Morniflumate、Nabumetone、Naproxen、Naproxen Sodium、Naproxol、Nimazone、Olsalazine Sodium、Orgotein、Orpanoxin、Oxaprozin、Oxyphenbutazone、Paranyline Hydrochloride、Pentosan Polysulfate Sodium、Phenbutazone Sodium Glycerate、Pirfenidone、Piroxicam、Piroxicam Cinnamate、Piroxicam Olamine、Pirprofen、Prednazate、Prifelone、Prodolic Acid、Proquazone、Proxazole、Proxazole Citrate、Rimexolone、Romazarit、Salcolex、Salnacedin、Salsalate、Salycilates、Sanguinarium Chloride、Seclazone、Sermetacin、Sudoxicam、Sulindac、Suprofen、Talmetacin、Talniflumate、Talosalate、Tebufelone、Tenidap、Tenidap Sodium、Tenoxicam、Tesicam、Tesimide、Tetrydamine、Tiopinac、Tixocortol Pivalate、Tolmetin、Tolmetin Sodium、Triclonide、Triflumidate、Zidometacin、Glucocorticoids、およびZomepirac Sodiumが挙げられる。1つの好ましい抗炎症薬剤はアルピリンである。
um、Retaplase、Trifenagrel、Warfarin、およびDextransが挙げられる。
eptor blocking agent)」は、狭心症、高血圧、および不整脈でのカテコールアミンの心血管効果と拮抗する薬剤のクラスである。βアドレナリン作動性レセプターブロッカーとしては、限定はされないが、atenolol、acebutolol、alprenolol、befunolol、betaxolol、bunitrolol、carteolol、celiprolol、hedroxalol、indenolol、labetalol、levobunolol、mepindolol、methypranol、metindol、metoprolol、metrizoranolol、oxprenolol、pindolol、propranolol、practolol、practolol、sotalolnadolol、tiprenolol、tomalolol、timolol、bupranolol、penbutolol、trimepranol、2−(3−(1,1−ジメチルエチル)−アミノ−2−ヒドロキシプロポキシ)−3−ピリジンカルボニトリルHCl、1−ブチルアミノ−3−(2,5−ジクロロフェノキシ)−2−プロパノール、1−イソプロピルアミノ−3−(4−(2−シクロプロピルメトキエチル)フェノキシ)−2−プロパノール、3−イソプロピルアミノ−1−(7−メチルインダン−4−イロキシ)−2−ブタノール、2−(3−t−ブチルアミノ−2−ヒドロキシ−プロピルチオ)−4−(5−カルバモイル−2−チエニル)チアゾール、7−(2−ヒドロキシ−3−t−ブチルアミノプロキシ)フタリドが挙げられる。異性混合物としてあるいはそれらそれぞれの左旋性または右旋性形態で上記に明らかにした化合物を用いることができる。
cyclooxygenase−2 cDNA and assays for evaluating cyclooxygenase−2 activity」を参照せよ)。この酵素は、COX−1とは異なる。COX−2は、マイトジェン、エンドトキシン、ホルモン、サイトカイン、および成長因子等の多数の因子によって、急速かつ容易に誘導可能である。プロスタグランジンが生理学的役割および病理学的役割の両方を有するので、構成性酵素であるCOX−1は、プロスタグランジンの内在性の基礎遊離の大部分を担っており、そのため、消化管完全性および腎血流量の維持等のその生理学的機能は重要である。対照的に、誘導性形態であるCOX−2は、プロスタグランジンの病理学的効果を主に担っており、この場合該酵素の迅速な誘導は、炎症性因子、ホルモン、成長因子、成長因子等の因子に応答して生じると考えられる。したがって、COX−2の選択的インヒビターは、従来の非ステロイド性抗炎症性薬剤と類似の抗炎症性、解熱性、および鎮痛性特性を有し、さらにホルモン誘導子宮収縮を阻害し、かつ潜在的抗癌効果も有するが、副作用は少ないと考えられる。特に、そのようなCOX−2インヒビターは、消化管毒性に対する潜在能力の減少、腎臓副作用の潜在能力の減少、出血時間への効果の減少、および恐らくアスピリン感受性喘息被験体で喘息発作を誘導する潜在能力の減少を有すると考
えられるので、本発明によって有用である。
heterocycles as COX−2 inhibitors」、米国特許第5,552,422号「Aryl substituted 5,5 fused aromatic nitrogen compounds as anti−inflammatory agents」、米国特許第5,604,253号「N−Benzylindol−3−yl propanoic acid derivatives as cyclooxygenase inhibitors」、米国特許第5,604,260号「5−Methanesulfonamido−1−indanones as an inhibitor of cyclooxygenase−2」、米国特許第5,639,780号「N−Benzyl indol−3−yl butanoic acid derivatives as cyclooxygenase inhibitors」、米国特許第5,677,318号「Diphenyl−1,2−3−thiadiazoles as anti−inflammatory agents」、米国特許第5,691,374号「Diaryl−5−oxygenated−2−(5H)−furanones as COX−2 inhibitors」、米国特許第5,698,584号「3,4−Diaryl−2−ヒドロキシ−2,5−dihydrofurans as prodrugs to COX−2 inhibitors」、米国特許第5,710,140号「Phenyl heterocycles as COX−2 inhibitors」、米国特許第5,733,909号「Diphenyl stilbenes as prodrugs to COX−2 inhibitors」、米国特許第5,789,413号「Alkylated styrenes as
prodrugs to COX−2 inhibitors」、米国特許第5,817,700号「Bisaryl cyclobutenes derivatives as cyclooxygenase inhibitors」、米国特許第5,849,943号「Stilbene derivatives useful as cyclooxygenase−2 inhibitors」、米国特許第5,861,419号「Substituted pyridines as selective cyclooxygenase−2 inhibitors」、米国特許第5,922,742号「Pyridinyl−2−cyclopenten−1−ones as selective cyclooxygenase−2 inhibitors」、米国特許第5,925,631号「Alkylated styrenes as prodrugs to COX−2 inhibitors」に記載されるに記載されるCOX−2インヒビターが含まれ、それら全てが通常は、Merck Frosst Canada,Inc.(Kirkland,CAまたはMerck & Co.,Inc.(Rahway,NJ)に譲渡されている。付加的なCOX−2インヒビターは、米国特許第5,643,933号にも記載されており、G.D.Searle & Co.(Skokie,IL)に譲渡される。表題は、「Substituted sulfonylphenylheterocycles as cyclooxygenase−2 and 5−lipoxygenase inhibitors.」である。
の変換によってその作用を発しする。上記に明らかにしたCOX−2インヒビタープロドラッグから形成された活性および選択的COX−2インヒビターは、1995年1月5日公表WO 95/00501、1995年7月13日公開WO 95/18799、および1995年12月12日発行米国特許第5,474,995号に詳細に記載されている。米国特許第5,543,297号、表題「Human cyclooxygenase−2 cDNA and assays for evaluating cyclooxygenase−2 activity」の教示を考慮して、当業者は、薬剤が選択的COX−2インヒビターであるかまたはCOX−2インヒビターの前駆体であるかを決定することができ、そのため、本発明の一部分である。
ンギオテンシン−(1−8)オクタペプチド、および関連類似体)、N置換イミダゾール−2−オン(米国特許第5,087,634号)、2−N−ブチル−4−クロロ−1−(2−クロロベンジル)、イミダゾール−5−酢酸を含むイミダゾールアセテート誘導体(Longら,J.Pharmacol.Exp.Ther.247(1),1−7(1988)を参照せよ)、4,5,6,7−テトラヒドロ−1H−イミダゾ[4,5−c]ピリジン−6−カルボキシル酸および類似誘導体(米国特許第4,816,463号)、N2−テトラゾール−β−グルクロニド類似体(米国特許第5,085,992号)、置換ピロール類、ピラゾール類、およびトリアゾール類(米国特許第5,081,127号)、1,3−イミダゾール等のフェノールおよび複素環式誘導体(米国特許第5,073,566号)、イミダゾール縮合7員環複素環(米国特許第5,064,825号)、ペプチド(例えば、米国特許第4,772,684号)、アンギオテンシンIIに対する抗体(例えば、米国特許第4,302,386号)、ならびにビフェニルメチル置換イミダゾール等のアラルキルイミダゾール化合物(例えば、欧州番号第253,310号、1998年1月20日)、ES8891(N−モルホリノアセチル−(−1−ナフチル)−L−アラニル−(4,チアゾリル)−L−アラニル(35,45)−4−アミノ−3−ヒドロキシ−5−シクロ−ヘキサペンタノイル−N−ヘキシルアミド,Sankyo Company,Ltd.,Tokyo,Japan)、SKF108566(E−α−2−[2−ブチル−1−(カルボキシフェニル)メチルl]1H−イミダゾール−5−イル[メチルアミン]−2−チオフェンプロパン酸,Smith Kline Beecham Pharmaceuticals,PA)、Losartan(DUP753/MK954,DuPont Merck Pharmaceutical Company)、Remikirin(RO42−5892,F.Hoffman LaRoche AG)、A2アゴニスト(Marion Merrill Dow)、ならびに特定の非ペプチド複素環(G.D.Searle and Company)が挙げられる。
導体(米国特許第5,104,869号および第5,095,119号);ジオールスルホンアミドおよびスルフィニル(米国特許第5,098,924号);修飾ペプチド(米国特許第5,095,006号);ペプチジルβ−アミノアシルアミノジオールカルバメート(米国特許第5,089,471号);ピロールイミダゾロン(米国特許第5,075,451号)、フッ素および塩素スタチン(statine)またはスタトン(statone)含有ペプチド(米国特許第5,066,643号);ペプチジルアミノジオール(米国特許第5,063,208号および第4,845,079号);N−モルホリノ誘導体(米国特許第5,055,466号);ペプスタチン誘導体(米国特許第4,980,283号);N−複素環式アルコール(米国特許第4,885,292号);レニンに対するモノクローナル抗体(米国特許第4,780,401号);ならびに種々の他のペプチドおよびそのアナログ(米国特許第5,071,837号、同第5,064,965号、同第5,063,207号、同第5,036,054号、同第5,036,053号、同第5,034,512号、および同第4,894,437号)である。
Mesylate);フェンプロクーモン;チンザパリン(tinzaparin)ナトリウム;およびワルファリンナトリウムが挙げられる。
の処置で有益であることが判明している(Endres M,ら,Proc Natl Acad Sci USA,1998,95:8880−5)。
い時間で連続的に、同時に投与することをいう。
駆体の送達およびその後のプローブ生成等の方法を用いて、所定のグリッドパターンで、基板上でプローブを直接合成する。
体媒介)捕獲によって選択的に測定することが可能である(例えば、選択的SELDI)。タンパク質スクリーニング(例えば、2−Dゲルを用いて)によって発見された遺伝子産物を、配列番号1および/または3由来の目的の特定マーカーを可視化するために最適化された「全タンパク質SELDI(total protein SELDI)」によって分解することができる。配列番号1および/または3間から得た複数のマーカーのSELDI測定からの腫瘍分類の予測モデルをSELDI戦略用に用いることが可能である。
(実験プロトコール:材料および方法)
(機械的歪みデバイス)
機械的に過負荷状態である心筋細胞の実験は、一般に、心臓周期を制御することなく細胞を引き伸ばすことによっておこなわれており、このアプローチは、収縮対弛緩での機械的過負荷間の区別が可能ではない。本研究では、本発明者らは、精密に制御された機械的歪みおよび培養心筋細胞での電気的ペーシングによって、とりわけどのように心筋細胞機械的伝達が心臓周期によって調節されるかを調査し、かつそのような調節に関与する遺伝子を同定することが可能になるユニークな実験システムを設計および構築した。
Packard Company,Palo Alto,CA)。制御回路を二部分に分割した:高電圧回路および低電圧またはデジタルシグナル回路。高電圧回路は、入力シグナルにもとづいて、出力を切り換えるゲートであった。低電圧回路は、コンピューターからの2つの制御シグナルを受信し、かつ加減抵抗器からのパルス幅を受け、該加減抵抗器は、正および負の電圧ゲート両方を制御した。低電圧回路は、0〜120V DC振幅および2〜37ms持続期間の間の電圧パルスを可能にした。光によって、パルスの連続的モニタリングが与えられ、回路のタイミングおよびキャリブレーションをオシロスコープによって確証した。
に対する正のコントロール)がこの時間点で誘導されるかを実証する先行試験にもとづいた。Affymatrix GeneChip RGU34A(Affymetrix,Inc.,Santa Clara,CA.)を用いて、DNAマイクロアレイハイブリダイゼーション実験を実行した。Affymatrixソフトウェアを用いて、データを分析した。
Cybernetics,Silver Springs,MD)を用いて、X線写真を走査および分析した。膜上のエチジウム染色28Sリボソームサブユニットに濃度測定ユニットを規格化した。
マイシンDは、2時間目および4時間目両方でIL1RL−1mRNA発現の誘導を阻害し、歪みに応答したIL1RL−1の誘導は、IL1RL−1の増加転写が原因であることが示唆された。タンパク質合成阻害剤であるシクロヘキサミドは、歪みに応答したIL1RL−1mRNA発現の誘導を阻害し、新規タンパク質合成がIL1RL−1mRNA発現の誘導に必要であることが示唆された。
(概要:)
サイトカインおよび心外傷。ストレス活性化サイトカインは、心外傷および病態生理学的症状の多くの形態に関与しており、最も特徴的なものは、腫瘍壊死因子−α、インターロイキン−1、およびインターロイキン−6である。これらの分子は、正常心臓で構成的には発現しないが、虚血および再灌流の間または血行力学的過負荷で急速に誘導され、それらがストレス、外傷、または成長刺激への初期心筋応答に重要な役割を果たしていることが示唆される(Mann DL,Cytokine and Growth Factor Reviews.1996;7:341−354;St.John Sutton
MG,ら Circulation.2000;101:2981−2988)。しかし、サイトカインは、虚血性心臓疾患および心不全を含む病的心筋症状で安定に発現することも判明しており、芳しくない予後に関連している(Pulkki KJ,ら Annals of Medicine.1997;29:339−343;Kubota T,ら,Proc Natl Acad.Sci.1998;95:6930−6935;Aukrust P,ら Am J Cardiol 1999;83:376−382;MacGowan GA,ら Am J Cardiol 1997;79:1128−1132;Roig E,ら Am J Cardiol 1998;688−690;Tsutamoto T,ら J Am Coll Cardiol 1998;31:391−398;Prabhu SD,ら Circulation.2000;101:2103−2109;Murray DR,ら Annu Rev Immunol.2000;18:451−494)。
検出されている(Gwechenberger M,ら Circulation 1999;99:546−551)。近年認識されていることは、インターロイキン−1シグナル伝達に付随する心臓疾患での反作用的な抗炎症性サイトカインの潜在的発現である。インターロイキン−4およびインターロイキン−10は、腫瘍壊死因子−αの合成を抑制し、腫瘍壊死因子に対するリガンドシンク(ligand sink)である可溶性腫瘍壊死因子レセプターの放出を高めることができる(Joyce DA.,1994;Eur.J.Immunol.11:2699−705)。インターロイキン−10は、心不全患者で増加し(Yamaoka M,ら Jpn Circ J 1999;63:951−956)、拡張型心筋症患者で、腫瘍壊死因子−α血清量が増加するとき、インターロイキン−10血清量が増加する(Ohtsuka T,ら J Am Coll Cardiol.2001;37:412−417)。
K,ら FEBS Letters.1993;318:83−87)。
J.Biochem.1997;121:95−103;Coyle AJ,ら J Exp Med.1999;190:895−902)。Tヘルパー2細胞は、感染に対する有益な応答を媒介するが、アレルギーおよび喘息の発症では有害である。T1/ST2の発現とTヘルパー2細胞でのインターロイキン−4産生との間には強い相関がある(Coyle AJ,ら J Exp Med.1999;190:895−902)。 T1/ST2は、Tヘルパー2への分化およびTヘルパー2の活性化に決定的な役割を果たしているが、Tヘルパー1細胞には果たしていない(O’Neill LAJ,ら Immunology Today.2000;21:206−209)。
Med.1999;190:895−902)。これらの試験によって、T1/ST2の発現は、インターロイキン−4、インターロイキン−5、およびインターロイキン−10の発現に有利に、サイトカインプロファイルを変化させることができることが示される。近年、インターロイキン−10は、心外傷の状況で抗炎症性効果を有することが判明した(Ohtsuka T,ら J Am Coll Cardiol 2001;37:412−417)。同様に、T1/ST2発現が欠如すると、心筋外傷後には有害であり得るインターフェロン−γ発現への移行が生じる可能性がある。
インビトロ試験。以下の試験によって、NF−κBの活性化を介していると考えられる機械的歪みおよびインターロイキン−1によるT1/ST2の誘導を実証する。より豊富な転写産物は可溶性アイソフォームであったが、T1/ST2の両転写産物(すなわち、IL1RL−1S可溶性転写産物およびIL1RL−1M膜転写産物)を心筋細胞での歪みによって誘導する。培養新生児心筋細胞での機械的歪みによって、T1/ST2mRNAを誘導する(図8)。
対する順位効果(rank order potency)は、PMA>歪み>インターロイキン−1βである。インターロイキン−1βは、NF−κBを介してシグナル伝達し、PMAはPKCを介するので、これらの結果によって、NFκBおよびPKC両方の活性化はT1/ST2の誘導に関与することが示唆される。
(材料および方法)
マウスでの実験的心筋梗塞。マウスに関する実験手順は、Harvard Medical School Standing Committee on Animalsによって認証された。先行して記載されるように冠動脈連結反応によって、実験的心筋梗塞をマウスで構築した(13)。冠動脈連結反応後1日および3日で心臓をマウスから採集して、その後Z−Fix(Anatech LTD)を用いて該心臓を潅流固定した。その後、Z−Fix中で心臓を一晩4℃で浸漬固定した。段階的エタノール溶液での脱水後、Histo−Clear(National Diagnostics)およびパラフィン包埋に心臓を入れた。5ミクロン組織切片を脱パラフィン処理し、再水和して、3%過酸化水素でインキュベートして、水ですすいだ後、リン酸緩衝食塩水ですすいだ。切片を阻害して、1:50抗マウスST2一次抗体(Morwell Diagnostics)および1:100抗ラットHRP結合二次抗体(Vector Laboratories)でインキュベートした。ヘマトキシリンおよびエオシンでスライドを対比染色した。
HEART試験。Healing and Early Afterload Reducing Therapy(HEART)試験は、米国およびカナダ内の36の施設から急性心筋梗塞(MI)である352人の患者を登録した無作為化二重盲検プラセボ対照試験であった。24時間以内にMIを経験した21歳を超える男性および女性が有資格者
であった。包含および除外基準、ならびに試験設計の詳細については先行して記載されている(Pfeffer M.A.,ら,Circulation,1997,95:2643−2651;Greaves S.C.,ら,Am.J.Cardiol,1997,80:442−448;Solomon S.D.,ら,Ann.Intern.Med.,2001,134:451−458;Aikawa Y.,ら,Am.Heart
J,2001,141:234−242)。69人の無作為に選ばれた患者由来の心筋梗塞後1日、14日、および90日目から得た連続血液試料がこの試験に利用可能であった。先行して記載される二重モノクローナルサンドイッチELISAアッセイを用いて、可溶性T1/ST2をアッセイした(Kuroiwa K.,ら,Hybridoma,2000,19:151−159)。該アッセイは、市販されている(MBL International,Watertown,MA)。
マウス内の心筋梗塞でのT1/ST2タンパク質のインビボ発現。外傷心筋でのT1/ST2の発現を評価するために、冠動脈連結反応を介して、マウスに実験的心筋梗塞を施した。図11は、心筋梗塞後1日および3日目のマウス心臓での免疫組織化学を用いたT1/ST2のタンパク質発現を示す。左心室の全ての領域、すなわち正常、梗塞、および境界地帯で、ポジティブ染色が心筋梗塞後(MI後)1日目に見られたが、心筋梗塞後3日目には見られなかった。T1/ST2に対する染色は、1日および3日目偽手術対照では観察されなかった。これらの結果によって、T1/ST2タンパク質は、3日目に見られる梗塞および境界地帯へのマクロファージの遊走前の梗塞後再構築(リモデリング)の早期位相中の急性外傷に応答して発現することが示唆される。これらの試験に用いたモノクローナル抗体は、T1/ST2の可溶型および膜型間の識別はしない。
07ng/ml;範囲0.02から3.53ng/ml;14日目対90日目P=NS)と比べて、心筋梗塞後1日目で有意に増加した(平均±標準誤差3.8±0.4ng/ml、p<0.001;範囲0.32から17.42ng/ml)。90日目の平均値は、健康な対照に対する公表平均値と類似であった(Kuroiwa K.,ら,Hybridoma,2000,19:151−159)。全身性T1/ST2タンパク質量は、図12bに示すピーククレアチンキナーゼ量(r=0.41、p<0.001)と正に相関していた。高全身性ST2タンパク質量も、図12cの四分位点分析(p=0.03)に示すように、心筋梗塞後1日目の低駆出率に関連していた。
、および基線ノルエピネフリン量(r=0.3854、p<0.0001)に相関していた(表2)。T1/ST2での変化(2週間目のT1/ST2量−試験登録時のT1/ST量)は、基線BNP(p<0.0001)および基線ProANP(p<0.0001)であるように、死亡率または移植の一変量の予測子として有意であった(p=0.048)(表3)。BNPおよびProANPを含む多変量モデルでは、T1/ST2での変化は、BNPおよびProANPから独立した死亡率または移植の独立予測子として依然として有意であった(表4)。
(方法)
試験集団。心筋梗塞での血栓崩壊(TIMI)14試験は、1997年3月〜1998年7月におこなわれたSTセグメント増加MIを有する患者に対する組み合わせ再灌流療法の無作為化非盲検用量範囲探索(dose−ranging)試験であった。特に、この試験は、4つの異なる血栓崩壊の組み合わせ(すなわちアブシキシマブ単独、アルテプラーゼ単独、アルテプラーゼの減少用量とともにアブシキシマブ、およびストレプトキナーゼの減少用量とともにアブシキシマブ)を比較する血管造影試験であった(Antman EMら,Circulation,1999;99:2720−32;Antman
EMら,Eur Heart J,2000;21:1944−53)。ENTIRE−TIMI23試験は、全量のテネクテプラーゼ(tenecteplase)およびアブシキシマブに加えた半分量のテネクテプラーゼ(tenecteplase)を含む薬理学的再灌流の様々な形態を用いた補助的抗トロンビン療法としてエノキサパリン(enoxaparin)を評価する、2000年2月〜2001年9月におこなわれた非盲検用量範囲探索(dose−ranging)の複数の試験機関にまたがった試験であった(Antman EMら,Circulation.2002;105:1642−9)。両試験では、患者は、6時間(ENTIRE)または12時間(TIMI 14)以内に少なくとも30分間の虚血性不快感に適格な症状発生を有し、かつ2つの隣接する前胸部心電図誘導(lead)で少なくとも0.1mV STセグメント増加を示した場合、包含されるに値した。両試験に対する除外基準としては、出血危険性の増加、重度の腎不全、および心臓性ショックが挙げられた。
心筋梗塞(STEMI)での死亡率の確立された予測子に対する期間を含むロジステイック回帰を用いて、治療結果とのST2の関連の多変量分析を実行した(Morrow,DAら,Circulation 2000;October 24;102(17):2031−7)。述べたところ以外では、提示する結果は、組み合わせたTIMI 14およびENTIRE−TIMI23試験集団に対するものである。
基線ST2および臨床変数。性別、年齢、体重、および冠動脈疾患の程度を含む大部分の基線臨床特性は、基線ST2量と相関しなかった(表5)。この集団での患者は、過去の病歴をほとんど持たないか、または心不全の臨床的根拠をほとんど示さなかった。興味深いことに、ST2量(p<0.0001)および収縮期血圧と正に相関する心拍数によって、ST量(p=0.05)との適度な相関が示され、ST2が生体力学的ストレス下で心筋細胞によって分泌されるという理論に整合している。生物マーカー心臓トロポニンI、BNP、およびCRPは、それら全てが心筋梗塞後の治療結果を予測することが判明(de Lemos JAら,N Engl J Med 2001;345:1014−21;Antman EM ら,N Engl J Med 1996;335:1342−9;Morrow DAら,J Am Coll Cardiol 1998;31:1460−5)しており、四分位点分析によってST2に相関し、心臓トロポニンIおよびCRPは、統計学的に有意であった。これらの生物マーカーを連続変数として評価したとき、定量的に弱い相関が観察された(表6)。
(表6 ST2および連続変数間の相関)
9)以外でN=448
ST2および臨床試験結果。810人の患者の組み合わせたコホートに対して、基線ST2は、30日目の臨床試験結果と有意に関連していた(表7)。特に、ST2量は、登録後30日目までに、その後死亡した患者(p=0.0001)、あるいは新規CHFを発症するかまたはCHFが悪化している患者(p=0.009)間の診察時で有意により高かった。ST2の平均増加基線量での二分は、30日間の追跡調査を通じて高くなった死亡率を示していた(ログランク(log−rank)、p=0.0009、図13)。さらに、ST2の四分位点分析では、死亡(p=0.001)および死亡またはCHFの複合(p=0.001)両方の危険性は、ST2のより高い量とともに段階的に階段状様式で増加した。ST2と臨床事象との間のこの関連は、2つの個々の試験(TIMI 14およびENTIRE−TIME23)間で一様であった。
ST2血清量の評価。四分位点分析した基線ST2量は、無作為化に対する時間に有意に相関していた(表5および6)。ST2量は、冠動脈閉塞後1日目に増加して、次の14日間で正常に戻ることが予期された(6)。TIMI 14患者のうち、228人の患者での血清ST2の連続測定の分析によって、時間とともに増加することが明らかになり、大部分の患者が12時間目にピークST2量に達したが、少数の患者は、この時間点を過ぎても増加し続けるST2血清量を有することが明らかになった。
果たすことが示唆される。これを考察するために、本発明者らは、急性心筋梗塞患者のコホートでの診察時に血清ST2量を測定した。その結果によって、これらの患者での診察時のST2量が院内および30日目死亡率に関連することが示される。さらに、多変量分析によって、ST2量は、重要な臨床因子に対する制御後の治療結果に独立して関連することが示された。
their extended family.Curr Opin Immunol.2002;14:117−22)は、急性心筋梗塞の初期事象に関与し得ることが示唆される。これらのデータは、心筋梗塞患者の予後を改良するための潜在的新規標的としてのこのレセプターを含意する。二次的には、ST2は、急性心筋梗塞患者での予後情報を提供する新規な生物マーカーを表す。したがって、ST2と心筋過負荷の別の状態である非虚血性うっ血性心不全の患者間の死亡率との間の関連を実証する本発明者らの先行研究が拡張される(Weinberg EO,Shimpo M,Hurwitz S,Tominaga S,Rouleau JL,Lee RT.Identification of serum soluble ST2 receptor as a novel heart failure biomarker.Circulation.2003;107:721−6)。
a novel heart failure biomarker.Circulation.2003;107:721−6)に加えて、喘息(Oshikawa K,Kuroiwa K,Tago K,Iwahana H,Yanagisawa K,Ohno S,Tominaga SI,Sugiyama Y.Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation.Am J Respir Crit Care Med.2001;164:277−81)、または全身性エリテマトーデス等の自己免疫疾患(Kuroiwa K,Arai T,Okazaki H,Minota S,Tominaga S.Identification of human ST2 protein in the sera of patients with autoimmune diseases.Biochem Biophys Res Commun.2001;284:1104−8)の患者もまた、増加血清ST2量を有し得る。したがって、そのような被験体での急性心筋梗塞の初期診断でのST2測定の有用性は疑問の余地がない。
当業者は、慣用的実験法に過ぎない方法を用いて、本明細書に記載した本発明の特定の実施形態に対する多くの等価物を認識するか、または確認し得る。そのような等価物を特許請求の範囲に包括することが意図される。
Claims (29)
- 被験体の心血管疾患の結果をインビトロで予測する方法であって、該方法が、以下:
被験体から得られた生物学的サンプル内の可溶性ST2タンパク質レベルを測定する工程、および
前記生物学的サンプル内の可溶性ST2タンパク質レベルと可溶性ST2タンパク質の対照レベルとを比較する工程、
を包含し、ここで、前記対照レベルと比較した前記生物学的サンプル内の可溶性ST2タンパク質レベルの増加がネガティブな結果を示し、かつ、前記対照レベルと比較した前記生物学的サンプル内の可溶性ST2タンパク質レベルの減少がポジティブな結果を示す、前記方法。 - 前記心血管疾患が、心肥大、心筋梗塞、卒中、および心不全からなる群から選択される、請求項1に記載の方法。
- 前記ネガティブな結果が、死亡および/または新規うっ血性心不全もしくはうっ血性心不全の悪化の危険性の上昇である、請求項1に記載の方法。
- 前記死亡の危険性の上昇が、院内の死亡である、請求項3に記載の方法。
- 前記ネガティブな結果が、30日内の死亡の危険性の上昇である、請求項3に記載の方法。
- 前記ネガティブな結果が、30日内の新規うっ血性心不全またはうっ血性心不全の悪化である、請求項3に記載の方法。
- 前記対照レベルが所定の値または健康な被験体での可溶性ST2タンパク質レベルである、請求項1に記載の方法。
- 前記可溶性ST2タンパク質のレベルが、虚血性不快感の症状発生の12時間以内に、またはその後の1、3、12もしくは24時間以内に測定される、請求項1に記載の方法。
- 前記可溶性ST2タンパク質のレベルが、虚血性不快感の症状発生の6時間以内に、またはその後の1、3、12もしくは24時間以内に測定される、請求項8に記載の方法。
- 前記生物学的サンプルが血液または血清を含む、請求項1に記載の方法。
- 被験体の心血管疾患の結果をインビトロで予測する方法であって、該方法が、以下:
第1の時点において前記被験体から得られた生物学的サンプル内の可溶性ST2タンパク質レベルを測定する工程、
第2の時点において前記被験体から得られた生物学的サンプル内の可溶性ST2タンパク質レベルを測定する工程、および
前記第1の時点において得られた生物学的サンプル内の可溶性ST2タンパク質レベルと、前記第2の時点において得られた生物学的サンプル内の可溶性ST2タンパク質レベルとを比較する工程、
を包含し、ここで、前記第2の時点において得られた生物学的サンプル内の可溶性ST2タンパク質レベルと比較した前記第1の時点において得られた生物学的サンプル内の可溶性ST2タンパク質レベルの変化が、心血管疾患の結果を示す、前記方法。 - 前記心血管疾患が、心肥大、心筋梗塞、卒中、および心不全からなる群から選択される、請求項11に記載の方法。
- 前記第1の時点が心筋梗塞の24時間以内である、請求項11に記載の方法。
- 前記第2の時点が前記第1の時点の2週間後である、請求項11または13に記載の方法。
- 前記第1の時点における可溶性ST2タンパク質レベルと比較した前記第2の時点における可溶性ST2タンパク質レベルの上昇が、死亡または移植の危険性の上昇を示す、請求項11に記載の方法。
- 前記被験体から得られた生物学的サンプル内の心血管疾患に関連する少なくとも一つの他のマーカーレベルを測定する工程をさらに含む、請求項1または11に記載の方法。
- 前記少なくとも一つの他のマーカーが、循環カテコールアミン、アンギオテンシンII、クレアチニン、クレアチンキナーゼMBイソ酵素(CK−MB)、C反応性タンパク質(CRP)、心臓トロポニンI、ナトリウム利尿ペプチド、または酸化ストレスのマーカーである、請求項16に記載の方法。
- 前記少なくとも一つの他のマーカーが、心臓トロポニンIおよび脳ナトリウム利尿ペプチド(BNP)である、請求項17に記載の方法。
- 前記循環カテコールアミンが、ノルエピネフリン、ドーパミン、またはエピネフリンである、請求項17に記載の方法。
- 前記ナトリウム利尿ペプチドが、脳ナトリウム利尿ペプチド(BNP)またはプロ心房ナトリウム利尿ペプチド(Pro−ANP)である、請求項17に記載の方法。
- 前記ナトリウム利尿ペプチドが、脳ナトリウム利尿ペプチド(BNP)である、請求項20に記載の方法。
- 前記酸化ストレスのマーカーが、アドレノルチンまたはマロンジアルデヒドである、請求項17に記載の方法。
- 前記第1の時点において得られた生物学的サンプルまたは前記第2の時点において得られた生物学的サンプルが、血液または血清を含む、請求項11に記載の方法。
- 前記被験体がヒトである、請求項1または11に記載の方法。
- 前記被験体が、高コレステロール血症、高トリグリセリド血症、高脂肪血症、喫煙者、または高血圧である、請求項24に記載の方法。
- 前記被験体が、虚血性疾患を有さない、請求項24に記載の方法。
- 前記被験体が、心血管疾患の治療を受けたことがある、または心血管疾患の治療を受けている、請求項24に記載の方法。
- 前記被験体が、心筋梗塞もしくは心不全の治療を受けたことがある、または心筋梗塞もしくは心不全の治療を受けている、請求項27に記載の方法。
- 前記可溶性ST2タンパク質が、配列番号2である、請求項1または11に記載の方法。
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Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002218026A1 (en) | 2000-11-09 | 2002-05-21 | The Brigham And Women's Hospital, Inc. | Cardiovascular disease diagnostic and therapeutic targets |
AU2003234407B2 (en) | 2002-05-09 | 2008-12-18 | The Brigham And Women's Hospital, Inc. | 1L1RL-1 as a cardiovascular disease marker and therapeutic target |
US7840263B2 (en) * | 2004-02-27 | 2010-11-23 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression |
EP1756554A4 (en) * | 2004-06-03 | 2009-04-29 | Vermillion Inc | BIOMARKERS FOR PERIPHERAL ARTERY DISEASE |
US7764995B2 (en) | 2004-06-07 | 2010-07-27 | Cardiac Pacemakers, Inc. | Method and apparatus to modulate cellular regeneration post myocardial infarct |
US7729761B2 (en) * | 2004-07-14 | 2010-06-01 | Cardiac Pacemakers, Inc. | Method and apparatus for controlled gene or protein delivery |
US7981065B2 (en) | 2004-12-20 | 2011-07-19 | Cardiac Pacemakers, Inc. | Lead electrode incorporating extracellular matrix |
US8060219B2 (en) | 2004-12-20 | 2011-11-15 | Cardiac Pacemakers, Inc. | Epicardial patch including isolated extracellular matrix with pacing electrodes |
US20070036770A1 (en) * | 2005-08-12 | 2007-02-15 | Wagner Darrell O | Biologic device for regulation of gene expression and method therefor |
US7774057B2 (en) | 2005-09-06 | 2010-08-10 | Cardiac Pacemakers, Inc. | Method and apparatus for device controlled gene expression for cardiac protection |
AU2012202069B2 (en) * | 2006-04-24 | 2015-11-05 | Critical Care Diagnostics, Inc. | Predicting mortality and detecting severe disease |
EP2386860B1 (en) | 2006-04-24 | 2014-11-05 | Critical Care Diagnostics, Inc. | Predicting mortality and detecting severe disease |
AU2013204539B2 (en) * | 2006-04-24 | 2015-11-05 | Critical Care Diagnostics, Inc. | Predicting mortality and detecting severe disease |
WO2007143295A2 (en) * | 2006-04-27 | 2007-12-13 | Critical Care Diagnostics, Inc. | Interleukin-33 (il-33) for the diagnosis and prognosis of cardiovascular disease |
AU2011203031B2 (en) * | 2006-05-01 | 2013-12-12 | Critical Care Diagnostics, Inc. | Diagnosis of cardiovascular disease |
EP2021796B1 (en) * | 2006-05-01 | 2012-02-08 | Critical Care Diagnostics, Inc. | Diagnosis of cardiovascular disease |
PL2019965T3 (pl) * | 2006-05-02 | 2015-10-30 | Critical Care Diagnostics Inc | Rozpoznawanie różnicowe chorób układu oddechowego i sercowo-naczyniowego |
WO2007130627A2 (en) * | 2006-05-04 | 2007-11-15 | The Brigham And Women's Hospital, Inc. | Il-33 in the treatment and diagnosis of diseases and disorders |
EP2019318A1 (en) * | 2007-07-27 | 2009-01-28 | Erasmus University Medical Center Rotterdam | Protein markers for cardiovascular events |
ES2809171T3 (es) | 2008-01-18 | 2021-03-03 | Harvard College | Métodos para detectar distintivos de enfermedades o afecciones en fluidos corporales |
SI2269063T1 (sl) | 2008-04-18 | 2014-01-31 | Critical Care Diagnostics, Inc. | Napoved tveganja večjih neugodnih pojavov na srcu |
EP2319924B1 (en) * | 2008-08-15 | 2016-03-09 | Fujikura Kasei Co., Ltd. | Polypeptide marker for diagnosis of arteriosclerosis, method for detection of arteriosclerosis by using the maker or the like, and kit for diagnosis of arteriosclerosis |
WO2010108180A2 (en) * | 2009-03-20 | 2010-09-23 | The Cleveland Clinic Foundation | Citrulline, a risk indicator for cardiovascular disease |
CN103154027B (zh) * | 2010-04-09 | 2016-06-29 | 重症监护诊断股份有限公司 | 可溶性人st-2抗体和分析法 |
CA2806304A1 (en) | 2010-07-23 | 2012-01-26 | President And Fellows Of Harvard College | Methods of detecting prenatal or pregnancy-related diseases or conditions |
AU2011280997A1 (en) | 2010-07-23 | 2013-02-28 | President And Fellows Of Harvard College | Methods of detecting autoimmune or immune-related diseases or conditions |
SG10201505723UA (en) | 2010-07-23 | 2015-09-29 | Harvard College | Methods for detecting signatures of disease or conditions in bodily fluids |
CN103124795A (zh) | 2010-07-23 | 2013-05-29 | 哈佛大学校长及研究员协会 | 利用吞噬细胞检测疾病或病症的方法 |
US20130210647A1 (en) | 2010-07-23 | 2013-08-15 | President And Fellows Of Harvard College | Methods of Detecting Cardiovascular Diseases or Conditions |
TW201238976A (en) | 2011-02-23 | 2012-10-01 | Hoffmann La Roche | Antibodies against human IL33R and uses thereof |
WO2012141844A2 (en) | 2011-03-17 | 2012-10-18 | Critical Care Diagnostics, Inc. | Methods predicting risk of an adverse clinical outcome |
CN106908604B (zh) * | 2011-07-18 | 2019-01-29 | 重症监护诊断股份有限公司 | 治疗心血管疾病和预测运动疗法功效的方法 |
SG11201400904SA (en) * | 2011-09-30 | 2014-04-28 | Somalogic Inc | Cardiovascular risk event prediction and uses thereof |
US20130157290A1 (en) * | 2011-12-16 | 2013-06-20 | Yves Levy | Soluble st2 as a marker for disease |
KR101411330B1 (ko) * | 2012-04-24 | 2014-06-25 | 연세대학교 산학협력단 | 감성 진단 칩과 그 측정장치 |
AR091069A1 (es) | 2012-05-18 | 2014-12-30 | Amgen Inc | Proteinas de union a antigeno dirigidas contra el receptor st2 |
WO2013173778A1 (en) | 2012-05-18 | 2013-11-21 | Critical Care Diagnostics, Inc. | Methods for treating or predicting risk of a ventricular tachyarrhythmia event |
ES2656897T3 (es) * | 2012-08-16 | 2018-02-28 | Critical Care Diagnostics, Inc. | Procedimientos de predicción del riesgo de desarrollar hipertensión |
IN2015DN01767A (ja) | 2012-08-21 | 2015-05-29 | Critical Care Diagnostics Inc | |
US9265458B2 (en) | 2012-12-04 | 2016-02-23 | Sync-Think, Inc. | Application of smooth pursuit cognitive testing paradigms to clinical drug development |
WO2014164366A1 (en) | 2013-03-09 | 2014-10-09 | Harry Stylli | Methods of detecting cancer |
US9380976B2 (en) | 2013-03-11 | 2016-07-05 | Sync-Think, Inc. | Optical neuroinformatics |
AU2014407088B2 (en) | 2014-09-26 | 2021-09-23 | Somalogic Operating Co., Inc. | Cardiovascular risk event prediction and uses thereof |
US10079073B2 (en) | 2014-12-11 | 2018-09-18 | Critical Care Diagnostics, Inc. | Test apparatus and methods for ST2 cardiac biomarker |
US10324089B2 (en) | 2014-12-11 | 2019-06-18 | Critical Care Diagnostics, Inc. | Test apparatus and methods for ST2 cardiac biomarker |
EP3446124A1 (en) * | 2016-04-18 | 2019-02-27 | Roche Diagnostics GmbH | Soluble st2 for the identification of progressors to lvh in the general population |
CN107446040B (zh) * | 2016-05-30 | 2021-01-12 | 深圳市安群生物工程有限公司 | 人st2抗原表位肽、抗原、抗体、试剂盒及应用 |
RU2649131C1 (ru) * | 2017-04-12 | 2018-03-29 | Федеральное государственное бюджетное научное учреждение "Томский национальный исследовательский медицинский центр Российской академии наук" (Томский НИМЦ) | Способ диагностики рестеноза стента коронарной артерии у больных ишемической болезнью сердца с хронической сердечной недостаточностью |
CN112074738A (zh) * | 2018-04-13 | 2020-12-11 | 共立制药股份有限公司 | 心力衰竭检测方法、心力衰竭检测用器具、夹心免疫检测法以及抗体的组合 |
RU2677611C1 (ru) * | 2018-04-16 | 2019-01-17 | Федеральное государственное бюджетное научное учреждение "Томский национальный исследовательский медицинский центр Российской академии наук" (Томский НИМЦ) | Способ прогнозирования неблагоприятных сердечно-сосудистых событий в течение 12 месяцев у больных хронической сердечной недостаточностью с рецидивом стенокардии после реваскуляризации миокарда |
CN108982871B (zh) * | 2018-07-19 | 2021-09-24 | 北京市心肺血管疾病研究所 | 血清sST2在小儿扩张型心肌病预后中的应用 |
RU2767266C1 (ru) * | 2021-05-27 | 2022-03-17 | Федеральное государственное бюджетное научное учреждение «Томский национальный исследовательский медицинский центр Российской академии наук» (Томский НИМЦ) | Способ прогнозирования однолетнего риска неблагоприятных сердечно-сосудистых событий у мужчин после декомпенсации хронической сердечной недостаточности с сохранной фракцией выброса левого желудочка сердца и синдромом обструктивного апноэ во сне |
CN114350670B (zh) * | 2022-03-18 | 2022-06-14 | 北京市心肺血管疾病研究所 | 特异性识别可溶性st2蛋白的核酸适配体及其应用 |
Family Cites Families (218)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3854480A (en) | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
US4302386A (en) | 1978-08-25 | 1981-11-24 | The Ohio State University | Antigenic modification of polypeptides |
US4105776A (en) | 1976-06-21 | 1978-08-08 | E. R. Squibb & Sons, Inc. | Proline derivatives and related compounds |
US4208479A (en) | 1977-07-14 | 1980-06-17 | Syva Company | Label modified immunoassays |
US4316906A (en) | 1978-08-11 | 1982-02-23 | E. R. Squibb & Sons, Inc. | Mercaptoacyl derivatives of substituted prolines |
IL58849A (en) | 1978-12-11 | 1983-03-31 | Merck & Co Inc | Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them |
US4231938A (en) | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
US4508729A (en) | 1979-12-07 | 1985-04-02 | Adir | Substituted iminodiacids, their preparation and pharmaceutical compositions containing them |
US4444784A (en) | 1980-08-05 | 1984-04-24 | Merck & Co., Inc. | Antihypercholesterolemic compounds |
US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
DK149080C (da) | 1980-06-06 | 1986-07-28 | Sankyo Co | Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre |
US4344949A (en) | 1980-10-03 | 1982-08-17 | Warner-Lambert Company | Substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids |
ZA817261B (en) | 1980-10-23 | 1982-09-29 | Schering Corp | Carboxyalkyl dipeptides,processes for their production and pharmaceutical compositions containing them |
US4675189A (en) | 1980-11-18 | 1987-06-23 | Syntex (U.S.A.) Inc. | Microencapsulation of water soluble active polypeptides |
US4337201A (en) | 1980-12-04 | 1982-06-29 | E. R. Squibb & Sons, Inc. | Phosphinylalkanoyl substituted prolines |
US4410520A (en) | 1981-11-09 | 1983-10-18 | Ciba-Geigy Corporation | 3-Amino-[1]-benzazepin-2-one-1-alkanoic acids |
GB2128984B (en) | 1982-05-12 | 1985-05-22 | Hoffmann La Roche | Diaza-bicyclic compounds |
US4739073A (en) | 1983-11-04 | 1988-04-19 | Sandoz Pharmaceuticals Corp. | Intermediates in the synthesis of indole analogs of mevalonolactone and derivatives thereof |
US4452775A (en) | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4780401A (en) | 1984-04-09 | 1988-10-25 | Ciba-Geigy Corporation | Novel monoclonal antibodies to human renin and hybridoma cells, processes for their preparation and their applications |
US4845079A (en) | 1985-01-23 | 1989-07-04 | Luly Jay R | Peptidylaminodiols |
US5066643A (en) | 1985-02-19 | 1991-11-19 | Sandoz Ltd. | Fluorine and chlorine statine or statone containing peptides and method of use |
US4894437A (en) | 1985-11-15 | 1990-01-16 | The Upjohn Company | Novel renin inhibiting polypeptide analogs containing S-aryl-D- or L- or DL-cysteinyl, 3-(arylthio)lactic acid or 3-(arylthio)alkyl moieties |
US4885292A (en) | 1986-02-03 | 1989-12-05 | E. R. Squibb & Sons, Inc. | N-heterocyclic alcohol renin inhibitors |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US4816463A (en) | 1986-04-01 | 1989-03-28 | Warner-Lambert Company | Substituted diimidazo [1,5-a: 4',5'-d]pyridines having antihypertensive activity |
US4940727A (en) | 1986-06-23 | 1990-07-10 | Merck & Co., Inc. | Novel HMG-CoA reductase inhibitors |
US5116870A (en) | 1986-06-23 | 1992-05-26 | Merck & Co., Inc. | HMG-CoA reductase inhibitors |
CA1334092C (en) | 1986-07-11 | 1995-01-24 | David John Carini | Angiotensin ii receptor blocking imidazoles |
US5075109A (en) | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
US4772684A (en) | 1987-01-20 | 1988-09-20 | Triton Biosciences, Inc. | Peptides affecting blood pressure regulation |
US4748024A (en) | 1987-04-06 | 1988-05-31 | Endocon, Inc. | Flash flow fused medicinal implants |
US4904646A (en) | 1987-05-22 | 1990-02-27 | E. R. Squibb & Sons, Inc. | Phosphorus-containing HMG-COA reductase inhibitors |
US5017716A (en) | 1987-05-22 | 1991-05-21 | E.R. Squibb & Sons, Inc. | Phosphorous-containing HMG-CoA reductase inhibitors, new intermediates and method |
US5091378A (en) | 1987-05-22 | 1992-02-25 | E. R. Squibb & Sons, Inc. | Phosphorus-containing HMG-CoA reductase inhibitors, new intermediates and method |
US4906624A (en) | 1987-09-08 | 1990-03-06 | Warner-Lambert Company | 6-(((Substituted)pyridin-3-yl)alkyl)-and alkenyl)-tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis |
US4997837A (en) | 1987-09-08 | 1991-03-05 | Warner-Lambert Company | 6-(((substituted)pyridin-3-yl)alkyl)-and alkenyl)-tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis |
US4980283A (en) | 1987-10-01 | 1990-12-25 | Merck & Co., Inc. | Renin-inhibitory pepstatin phenyl derivatives |
US5089471A (en) | 1987-10-01 | 1992-02-18 | G. D. Searle & Co. | Peptidyl beta-aminoacyl aminodiol carbamates as anti-hypertensive agents |
US5034512A (en) | 1987-10-22 | 1991-07-23 | Warner-Lambert Company | Branched backbone renin inhibitors |
US5063207A (en) | 1987-10-26 | 1991-11-05 | Warner-Lambert Company | Renin inhibitors, method for using them, and compositions containing them |
US5055466A (en) | 1987-11-23 | 1991-10-08 | E. R. Squibb & Sons, Inc. | N-morpholino derivatives and their use as anti-hypertensive agents |
US4929620A (en) | 1987-12-10 | 1990-05-29 | Warner-Lambert Company | 5-pyrimidinyl-3,5-dihydroxy-6-heptenoic acid compounds useful as inhibitors of cholesterol biosynthesis |
US5674722A (en) | 1987-12-11 | 1997-10-07 | Somatix Therapy Corporation | Genetic modification of endothelial cells |
US4994494A (en) | 1987-12-21 | 1991-02-19 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | HMG-COA reductase inhibitors |
US4900754A (en) | 1987-12-21 | 1990-02-13 | Rorer Pharmaceutical Corp. | HMG-COA reductase inhibitors |
US4939143A (en) | 1987-12-21 | 1990-07-03 | Rorer Pharmaceutical Corporation | Substituted cyclohexene derivatives as HMG-CoA reductase inhibitors |
US5001128A (en) | 1987-12-21 | 1991-03-19 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | HMG-COA reductase inhibitors |
US5001144A (en) | 1987-12-21 | 1991-03-19 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted cyclohexene derivatives as HMG-CoA reductase inhibitors |
US5081127A (en) | 1988-01-07 | 1992-01-14 | E. I. Du Pont De Nemours And Company | Substituted 1,2,3-triazole angiotensin II antagonists |
US4946864A (en) | 1988-02-01 | 1990-08-07 | Merck & Co., Inc. | Novel HMG-CoA reductase inhibitors |
US5036054A (en) | 1988-02-11 | 1991-07-30 | Warner-Lambert Company | Renin inhibitors containing alpha-heteroatom amino acids |
DE68914495T2 (de) | 1988-03-02 | 1994-10-27 | Merck & Co Inc | Antihypercholesterolemisches Mittel. |
US5021453A (en) | 1988-03-02 | 1991-06-04 | Merck & Co., Inc. | 3-keto HMG-CoA reductase inhibitors |
US4920109A (en) | 1988-04-18 | 1990-04-24 | Merck & Co., Inc. | Antifungal compositions and method of controlling mycotic infections |
US5166171A (en) | 1988-05-13 | 1992-11-24 | Hoechst Aktiengesellschaft | 6-phenoxymethyl-4-hydroxytetrahydropyran-2-ones and 6-thiphenoxymethyl-4-hydroxytetrahydropyran-2-ones and the corresponding dihydroxycarboxylic acid derivatives, salts and esters, and in treating hypercholesterolemia |
US5036053A (en) | 1988-05-27 | 1991-07-30 | Warner-Lambert Company | Diol-containing renin inhibitors |
US5206140A (en) | 1988-06-24 | 1993-04-27 | Research Corporation Technologies, Inc. | Assay for soluble crosslinked fibrin polymers |
US4897402A (en) | 1988-06-29 | 1990-01-30 | Merck & Co., Inc. | 5-oxa, 5-thia, 5-aza HmG-CoA reductase inhibitors |
US4963538A (en) | 1988-06-29 | 1990-10-16 | Merck & Co., Inc. | 5-oxygenated HMG-CoA reductase inhibitors |
IT1226726B (it) | 1988-07-29 | 1991-02-05 | Zambon Spa | Composti attivi come inibitori della biosintesi del colesterolo. |
US5196440A (en) | 1988-07-29 | 1993-03-23 | Zambon Group S.P.A. | Compounds active as inhibitors of the cholesterol biosynthesis |
DE3832570A1 (de) | 1988-09-24 | 1990-03-29 | Hoechst Ag | 7-substituierte derivate der 3,5-dihydroxyhept-6-insaeure, verfahren zur ihrer herstellung, ihre verwendung als arzneimittel, sowie zwischenprodukte |
EP0397834B1 (en) | 1988-10-28 | 2000-02-02 | Genentech, Inc. | Method for identifying active domains and amino acid residues in polypeptides and hormone variants |
DE3841520A1 (de) | 1988-12-09 | 1990-06-13 | Hoechst Ag | Enzymhemmende harnstoffderivate von dipeptiden, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung |
US4950675A (en) | 1988-12-21 | 1990-08-21 | Warner-Lambert Company | Pyridine di-mevalono-lactones as inhibitors of cholesterol biosynthesis |
US4957940A (en) | 1988-12-21 | 1990-09-18 | Warner-Lambert Company | Bicyclo heptane and bicyclo octane substituted inhibitors of cholesterol synthesis |
US4906657A (en) | 1988-12-21 | 1990-03-06 | Warner-Lambert Company | Bicyclo heptane and bicyclo octane substituted inhibitors of cholesterol synthesis |
US5106835A (en) | 1988-12-27 | 1992-04-21 | American Cyanamid Company | Renin inhibitors |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US4923861A (en) | 1989-02-07 | 1990-05-08 | Warner-Lambert Company | 6-(2-(2-(Substituted amino)-3-quinolinyl) ethenyl and ethyl) tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis |
US5130306A (en) | 1989-03-13 | 1992-07-14 | Merck & Co., Inc. | 5-Oxygenated HMG-COA reductase inhibitors |
US5132312A (en) | 1989-03-27 | 1992-07-21 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted cyclohexene derivatives as HMG-CoA reductase inhibitors |
US5133974A (en) | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
DE4004820A1 (de) | 1989-08-05 | 1991-04-25 | Bayer Ag | Renininhibitoren, verfahren zur herstellung und ihre verwendung in arzneimitteln |
US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
US5064825A (en) | 1989-06-01 | 1991-11-12 | Merck & Co., Inc. | Angiotensin ii antagonists |
JPH0731479Y2 (ja) | 1989-06-02 | 1995-07-19 | 内橋エステック株式会社 | 温度ヒューズ |
US5102911A (en) | 1989-06-09 | 1992-04-07 | Merck & Co, Inc. | 4-Substituted HMG-CoA reductase inhibitors |
US4970231A (en) | 1989-06-09 | 1990-11-13 | Merck & Co., Inc. | 4-substituted HMG-CoA reductase inhibitors |
FI94339C (fi) | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
US5063208A (en) | 1989-07-26 | 1991-11-05 | Abbott Laboratories | Peptidyl aminodiol renin inhibitors |
US4992429A (en) | 1989-08-24 | 1991-02-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Novel HMG-COA reductase inhibitors |
US5098931A (en) | 1989-08-31 | 1992-03-24 | Merck & Co., Inc. | 7-substituted HMG-CoA reductase inhibitors |
US5098924A (en) | 1989-09-15 | 1992-03-24 | E. R. Squibb & Sons, Inc. | Diol sulfonamide and sulfinyl renin inhibitors |
US5104869A (en) | 1989-10-11 | 1992-04-14 | American Cyanamid Company | Renin inhibitors |
US4946860A (en) | 1989-11-03 | 1990-08-07 | Rorer Pharmaceutical Corporation | Benzothiopyranyl derivatives as HMG-CoA reductase inhibitors |
US5114937A (en) | 1989-11-28 | 1992-05-19 | Warner-Lambert Company | Renin inhibiting nonpeptides |
US5073566A (en) | 1989-11-30 | 1991-12-17 | Eli Lilly And Company | Angiotensin ii antagonist 1,3-imidazoles and use thereas |
IT1237793B (it) | 1989-12-21 | 1993-06-17 | Zambon Spa | Composti attivi come inibitori dell'enzima hmg-coa reduttasi |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
US5025000A (en) | 1990-03-02 | 1991-06-18 | E. R. Squibb & Sons, Inc. | Phosphorus-containing HMG-CoA reductase inhibitor compounds |
US5095119A (en) | 1990-03-08 | 1992-03-10 | American Home Products Corporation | Renin inhibitors |
US5064965A (en) | 1990-03-08 | 1991-11-12 | American Home Products Corporation | Renin inhibitors |
US5075451A (en) | 1990-03-08 | 1991-12-24 | American Home Products Corporation | Pyrrolimidazolones useful as renin inhibitors |
US5622985A (en) | 1990-06-11 | 1997-04-22 | Bristol-Myers Squibb Company | Method for preventing a second heart attack employing an HMG CoA reductase inhibitor |
US5789163A (en) * | 1990-06-11 | 1998-08-04 | Nexstar Pharmaceuticals, Inc. | Enzyme linked oligonucleotide assays (ELONAS) |
US5085992A (en) | 1990-07-19 | 1992-02-04 | Merck & Co., Inc. | Microbial transformation process for antihypertensive products |
US5217899A (en) | 1990-08-24 | 1993-06-08 | The General Hospital Corporation | Cell stretching apparatus |
US5112857A (en) | 1990-09-04 | 1992-05-12 | Merck & Co., Inc. | Hmg-coa reductase inhibitor metabolites |
GB9019812D0 (en) | 1990-09-11 | 1990-10-24 | Scotgen Ltd | Novel antibodies for treatment and prevention of infection in animals and man |
US5087634A (en) | 1990-10-31 | 1992-02-11 | G. D. Searle & Co. | N-substituted imidazol-2-one compounds for treatment of circulatory disorders |
US5071837A (en) | 1990-11-28 | 1991-12-10 | Warner-Lambert Company | Novel renin inhibiting peptides |
US5182298A (en) | 1991-03-18 | 1993-01-26 | Merck & Co., Inc. | Cholesterol lowering agents |
US5256689A (en) | 1991-05-10 | 1993-10-26 | Merck & Co., Inc. | Cholesterol lowering compounds |
US5135935A (en) | 1991-05-17 | 1992-08-04 | Merck & Co., Inc. | Squalene synthetase inhibitors |
US5250435A (en) | 1991-06-04 | 1993-10-05 | Merck & Co., Inc. | Mutant strains of Aspergillus terreus for producing 7-[1,2,6,7,8,8a(R)-hexa-hydro-2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid),I) |
US5202327A (en) | 1991-07-10 | 1993-04-13 | E. R. Squibb & Sons, Inc. | Phosphorus-containing hmg-coa reductase inhibitors |
JP2665850B2 (ja) | 1991-11-14 | 1997-10-22 | 塩野義製薬株式会社 | hBNPのC端を認識するモノクロ−ナル抗体 |
US5407686A (en) | 1991-11-27 | 1995-04-18 | Sidmak Laboratories, Inc. | Sustained release composition for oral administration of active ingredient |
HU217629B (hu) | 1991-12-12 | 2000-03-28 | Novartis Ag. | Eljárás fluvasztatint tartalmazó stabilizált gyógyszerkészítmények előállítására |
US5260332A (en) | 1992-02-07 | 1993-11-09 | Merci & Co., Inc. | Cholesterol lowering compounds |
US5262435A (en) | 1992-02-10 | 1993-11-16 | Merck & Co., Inc. | Cholesterol lowering compounds |
US5286895A (en) | 1992-02-19 | 1994-02-15 | Merck & Co., Inc. | Cholesterol lowering compounds |
US5302604A (en) | 1992-03-09 | 1994-04-12 | Merck & Co., Inc. | Cholesterol lowering compounds produced by directed biosynthesis |
GB9211686D0 (en) | 1992-06-03 | 1992-07-15 | Medisinsk Innovation A S | Chemical compounds |
US5369125A (en) | 1992-07-17 | 1994-11-29 | Merck & Co., Inc. | Cholesterol-lowering agents |
US5283256A (en) | 1992-07-22 | 1994-02-01 | Merck & Co., Inc. | Cholesterol-lowering agents |
US5317031A (en) | 1992-10-19 | 1994-05-31 | Merck & Co., Inc. | Cholesterol lowering compounds |
US5604260A (en) | 1992-12-11 | 1997-02-18 | Merck Frosst Canada Inc. | 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2 |
JP2732005B2 (ja) | 1992-12-14 | 1998-03-25 | 眞一 富永 | ヒトst2をコードするdna、該dnaの発現産物、該dnaを発現させることによる発現産物の製造方法 |
US5543297A (en) | 1992-12-22 | 1996-08-06 | Merck Frosst Canada, Inc. | Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity |
JPH0731479A (ja) | 1993-02-23 | 1995-02-03 | Shinichi Tominaga | マウスst2lをコードするdna、該dnaの発現産物、該dnaを発現させることによる発現産物の製造方法 |
GB9602877D0 (en) | 1996-02-13 | 1996-04-10 | Merck Frosst Canada Inc | 3,4-Diaryl-2-hydroxy-2,5- dihydrofurans as prodrugs to cox-2 inhibitors |
US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
WO1995018799A1 (en) | 1994-01-10 | 1995-07-13 | Merck Frosst Canada Inc. | Phenyl heterocycles as cox-2 inhibitors |
WO1995024929A2 (en) | 1994-03-15 | 1995-09-21 | Brown University Research Foundation | Polymeric gene delivery system |
US5521213A (en) | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
CA2200462A1 (en) | 1994-10-27 | 1996-05-09 | Merck Frosst Canada Inc. | Stilbene derivatives useful as cyclooxygenase-2 inhibitors |
US5552422A (en) | 1995-01-11 | 1996-09-03 | Merck Frosst Canada, Inc. | Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents |
US6066322A (en) | 1995-03-03 | 2000-05-23 | Millennium Pharmaceuticals, Inc. | Methods for the treatment of immune disorders |
US5691374A (en) | 1995-05-18 | 1997-11-25 | Merck Frosst Canada Inc. | Diaryl-5-oxygenated-2-(5H) -furanones as COX-2 inhibitors |
US5639780A (en) | 1995-05-22 | 1997-06-17 | Merck Frosst Canada, Inc. | N-benzyl indol-3-yl butanoic acid derivatives as cyclooxygenase inhibitors |
US5604253A (en) | 1995-05-22 | 1997-02-18 | Merck Frosst Canada, Inc. | N-benzylindol-3-yl propanoic acid derivatives as cyclooxygenase inhibitors |
US5643933A (en) | 1995-06-02 | 1997-07-01 | G. D. Searle & Co. | Substituted sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors |
US5643599A (en) | 1995-06-07 | 1997-07-01 | President And Fellows Of Harvard College | Intracellular delivery of macromolecules |
US5736152A (en) | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
US5733909A (en) | 1996-02-01 | 1998-03-31 | Merck Frosst Canada, Inc. | Diphenyl stilbenes as prodrugs to COX-2 inhibitors |
US5789413A (en) | 1996-02-01 | 1998-08-04 | Merck Frosst Canada, Inc. | Alkylated styrenes as prodrugs to COX-2 inhibitors |
GB9607503D0 (en) | 1996-04-11 | 1996-06-12 | Merck Frosst Canada Inc | Bisaryl cyclobutenes derivatives as cyclooxygenase inhibitors |
US5922742A (en) | 1996-04-23 | 1999-07-13 | Merck Frosst Canada | Pyridinyl-2-cyclopenten-1-ones as selective cyclooxygenase-2 inhibitors |
US5677318A (en) | 1996-07-11 | 1997-10-14 | Merck Frosst Canada, Inc. | Diphenyl-1,2-3-thiadiazoles as anti-inflammatory agents |
US5861419A (en) | 1996-07-18 | 1999-01-19 | Merck Frosst Canad, Inc. | Substituted pyridines as selective cyclooxygenase-2 inhibitors |
AU7235296A (en) * | 1996-08-23 | 1998-03-06 | Human Genome Sciences, Inc. | T1 receptor-like ligand ii |
EP0981619A1 (en) * | 1997-02-28 | 2000-03-01 | Human Genome Sciences, Inc. | T1/st2-receptor ligand iii |
DE19711932A1 (de) | 1997-03-21 | 1998-09-24 | Anne Katrin Dr Werenskiold | In vitro-Verfahren zum Prognostizieren des Krankheitsverlaufs von Patienten mit Mammakarzinom und/oder zum Diagnostizieren eines Mammakarzinoms |
PT1003501E (pt) | 1997-04-02 | 2005-07-29 | Brigham & Womens Hospital | Utilizacao de um agente para reduzir o risco de doencas cardiovasculares |
WO1998057179A1 (en) | 1997-06-10 | 1998-12-17 | Medlyte Diagnostics, Inc. | Methods for early detection of heart disease |
ATE315228T1 (de) | 1997-09-11 | 2006-02-15 | Shionogi & Co | Immunoassay zum bestimmen von bnp |
GB9727172D0 (en) | 1997-12-24 | 1998-02-25 | Univ Glasgow | Reagents specific for st2l and uses therefor |
US6180597B1 (en) | 1998-03-19 | 2001-01-30 | Brigham And Women's Hospital, Inc. | Upregulation of Type III endothelial cell nitric oxide synthase by rho GTPase function inhibitors |
AU4990599A (en) | 1998-07-14 | 2000-02-07 | Brigham And Women's Hospital | Upregulation of type iii endothelial cell nitric oxide synthase by agents that disrupt actin cytoskeletal organization |
US6309888B1 (en) | 1998-09-04 | 2001-10-30 | Leuven Research & Development Vzw | Detection and determination of the stages of coronary artery disease |
GB9827348D0 (en) | 1998-12-12 | 1999-02-03 | Univ Leicester | Natriuretic peptide |
WO2000035473A2 (en) | 1998-12-18 | 2000-06-22 | Scios Inc. | Methods for detection and use of differentially expressed genes in disease states |
AU5309600A (en) | 1999-06-02 | 2000-12-18 | Millennium Pharmaceuticals, Inc. | Compositions and methods for the treatment and diagnosis of immune disorders |
FR2795823B1 (fr) | 1999-07-01 | 2001-11-23 | Inst Nat Sante Rech Med | Methodes et kits pour le diagnostic ou le suivi d'une pathologie synoviale ou osteoarticulaire comprenant l'utilisation d'un marqueur specifique de la degradation du tissu synovial |
US6323334B1 (en) * | 1999-09-24 | 2001-11-27 | Millennium Pharmaceuticals, Inc. | Nucleic acid molecules encoding a 103 gene product and uses therefor |
AU2001218871A1 (en) * | 2000-03-21 | 2001-10-03 | Takao Arai | Monoclonal antibody and method and kit for the immunoassay of soluble human st2 with the use of the same |
FR2807170B1 (fr) | 2000-03-30 | 2002-06-28 | Sipal | Charniere elastique a frottement reduit |
BR0107157A (pt) | 2000-08-22 | 2002-07-16 | Brigham And Womens Hospital In | Diagnose e tratamento de condições cardiovasculares |
AU2002218026A1 (en) | 2000-11-09 | 2002-05-21 | The Brigham And Women's Hospital, Inc. | Cardiovascular disease diagnostic and therapeutic targets |
US6537221B2 (en) | 2000-12-07 | 2003-03-25 | Koninklijke Philips Electronics, N.V. | Strain rate analysis in ultrasonic diagnostic images |
FI20010019A (fi) | 2001-01-05 | 2002-07-06 | Biohit Oyj | Menetelmä atrofisen diagnostisoimiseksi |
US7713705B2 (en) | 2002-12-24 | 2010-05-11 | Biosite, Inc. | Markers for differential diagnosis and methods of use thereof |
US20040253637A1 (en) | 2001-04-13 | 2004-12-16 | Biosite Incorporated | Markers for differential diagnosis and methods of use thereof |
AU2002305394A1 (en) | 2001-05-04 | 2002-11-18 | Biosite, Inc. | Diagnostic markers of acute coronary syndromes and methods of use thereof |
US6905827B2 (en) | 2001-06-08 | 2005-06-14 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing or monitoring auto immune and chronic inflammatory diseases |
WO2003022987A2 (en) | 2001-07-26 | 2003-03-20 | Eos Biotechnology, Inc. | Methods of diagnosis of hepatitis c infection, compositions and methods of screening for modulators of hepatitis c infection |
US6810284B1 (en) | 2001-11-21 | 2004-10-26 | Pacesetter, Inc. | Implantable cardiac stimulation system and method for monitoring diastolic function |
AU2003234407B2 (en) | 2002-05-09 | 2008-12-18 | The Brigham And Women's Hospital, Inc. | 1L1RL-1 as a cardiovascular disease marker and therapeutic target |
WO2003100000A2 (en) | 2002-05-24 | 2003-12-04 | Tularik Inc. | Amplification and overexpression of oncogenes |
US8263325B2 (en) | 2002-11-15 | 2012-09-11 | Ottawa Heart Institute Research Corporation | Predicting, detecting and monitoring treatment of cardiomyopathies and myocarditis |
WO2004056868A2 (en) | 2002-12-19 | 2004-07-08 | Endocube Sas | Nf-hev compositions and methods of use |
US20040133079A1 (en) | 2003-01-02 | 2004-07-08 | Mazar Scott Thomas | System and method for predicting patient health within a patient management system |
US20040220155A1 (en) | 2003-03-28 | 2004-11-04 | Pharmacia Corporation | Method of providing a steroid-sparing benefit with a cyclooxygenase-2 inhibitor and compositions therewith |
WO2005041893A2 (en) | 2003-10-31 | 2005-05-12 | Queststar Medical, Inc. | Detection of acute myocardial infarction biomarkers |
CA3048093A1 (en) | 2003-11-26 | 2005-06-23 | Celera Corporation | Single nucleotide polymorphisms associated with cardiovascular disorders and statin response, methods of detection and uses thereof |
JP4625812B2 (ja) | 2003-12-05 | 2011-02-02 | ザ クリーブランド クリニック ファウンデーション | 心臓血管疾患に対するリスクマーカー |
US20050196817A1 (en) | 2004-01-20 | 2005-09-08 | Molecular Staging Inc. | Biomarkers for sepsis |
NZ549040A (en) | 2004-02-17 | 2009-07-31 | Schering Corp | Use for interleukin-33 (IL33) and the IL-33 receptor complex |
JP2005291899A (ja) | 2004-03-31 | 2005-10-20 | Akira Matsumori | 心疾患の検査法 |
US8510225B2 (en) | 2004-09-01 | 2013-08-13 | Research In Motion Limited | Split channel authenticity queries in multi-party dialog |
ES2316044T3 (es) | 2005-01-24 | 2009-04-01 | F. Hoffmann-La Roche Ag | El uso de hormonas cardiacas para evaluar un riesgo cardiovascular con respecto a la administracion de farmacos antiinflamatorios. |
EP1731910A1 (en) | 2005-06-07 | 2006-12-13 | F. Hoffmann-La Roche Ag | Use of NT-proANP and NT-proBNP for diagnosing cardiac diseases |
US20070021977A1 (en) | 2005-07-19 | 2007-01-25 | Witt Biomedical Corporation | Automated system for capturing and archiving information to verify medical necessity of performing medical procedure |
JP4820192B2 (ja) | 2006-03-17 | 2011-11-24 | 一般財団法人化学及血清療法研究所 | 急性冠症候群でのadamts13の測定と利用 |
EP2386860B1 (en) | 2006-04-24 | 2014-11-05 | Critical Care Diagnostics, Inc. | Predicting mortality and detecting severe disease |
WO2007143295A2 (en) | 2006-04-27 | 2007-12-13 | Critical Care Diagnostics, Inc. | Interleukin-33 (il-33) for the diagnosis and prognosis of cardiovascular disease |
EP2021796B1 (en) | 2006-05-01 | 2012-02-08 | Critical Care Diagnostics, Inc. | Diagnosis of cardiovascular disease |
PL2019965T3 (pl) | 2006-05-02 | 2015-10-30 | Critical Care Diagnostics Inc | Rozpoznawanie różnicowe chorób układu oddechowego i sercowo-naczyniowego |
WO2007130627A2 (en) | 2006-05-04 | 2007-11-15 | The Brigham And Women's Hospital, Inc. | Il-33 in the treatment and diagnosis of diseases and disorders |
RU2312591C1 (ru) | 2006-06-14 | 2007-12-20 | Государственное образовательное учреждение высшего профессионального образования "Санкт-Петербургская государственная медицинская академия им. И.И. Мечникова Федерального агентства по здравоохранению и социальному развитию" | Способ прогнозирования развития риска внезапной смерти у больных с лево- и правожелудочковой экстрасистолией |
US20080233191A1 (en) | 2007-03-22 | 2008-09-25 | Brent Blackburn | Use of ranolazine for elevated brain-type natriuretic peptide |
JP2010526555A (ja) | 2007-05-11 | 2010-08-05 | タフツ・メディカル・センター | 加齢関連黄斑変性と関係するポリヌクレオチド及び患者のリスクを評価する方法 |
GB0713404D0 (en) | 2007-07-11 | 2007-08-22 | Integra Sp Ipr Ltd | Altio graph |
WO2009040133A1 (en) | 2007-09-26 | 2009-04-02 | Universitätsklinikum Heidelberg | Osteopontin as novel prognostic biomarker for heart failure |
FR2923029B1 (fr) | 2007-10-26 | 2009-11-20 | Minima | Lunettes de type sans entourage a branches filaires |
SI2269063T1 (sl) | 2008-04-18 | 2014-01-31 | Critical Care Diagnostics, Inc. | Napoved tveganja večjih neugodnih pojavov na srcu |
ES2431358T3 (es) | 2008-11-11 | 2013-11-26 | B.R.A.H.M.S Gmbh | Pronóstico y evaluación del riesgo en pacientes que padecen insuficiencia cardíaca mediante la determinación de la concentración de ADM |
EP2499489B1 (en) | 2009-11-13 | 2015-01-07 | BG Medicine, Inc. | Risk factors and prediction of myocardial infarction |
CN103154027B (zh) | 2010-04-09 | 2016-06-29 | 重症监护诊断股份有限公司 | 可溶性人st-2抗体和分析法 |
EP2635904A1 (en) | 2010-11-01 | 2013-09-11 | B.R.A.H.M.S GmbH | Prognosis and risk assessment of patients with non-specific complaints |
RU2452394C1 (ru) | 2010-11-09 | 2012-06-10 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования Ульяновский государственный университет | Способ прогнозирования риска смерти больных хронической сердечной недостаточностью |
WO2012141844A2 (en) | 2011-03-17 | 2012-10-18 | Critical Care Diagnostics, Inc. | Methods predicting risk of an adverse clinical outcome |
CN106908604B (zh) | 2011-07-18 | 2019-01-29 | 重症监护诊断股份有限公司 | 治疗心血管疾病和预测运动疗法功效的方法 |
WO2013173778A1 (en) | 2012-05-18 | 2013-11-21 | Critical Care Diagnostics, Inc. | Methods for treating or predicting risk of a ventricular tachyarrhythmia event |
ES2656897T3 (es) | 2012-08-16 | 2018-02-28 | Critical Care Diagnostics, Inc. | Procedimientos de predicción del riesgo de desarrollar hipertensión |
IN2015DN01767A (ja) | 2012-08-21 | 2015-05-29 | Critical Care Diagnostics Inc | |
JP6178687B2 (ja) | 2013-09-27 | 2017-08-09 | 富士機械工業株式会社 | グラビア塗工装置 |
CN106461636A (zh) | 2014-01-10 | 2017-02-22 | 重症监护诊断股份有限公司 | 用于测定心力衰竭风险的方法和系统 |
USD770057S1 (en) | 2014-04-14 | 2016-10-25 | Critical Care Diagnostics, Inc. | Blood test kit |
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