著者
後藤 祐児 萩原 義久
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 (ISSN:09157441)
巻号頁・発行日
vol.10, no.6, pp.457-462, 1999-12-01 (Released:2010-08-05)
参考文献数
9
被引用文献数
1 1 1
著者
村嶋 正幸 成田 有吾 岩崎 英一 橋爪 永子 出口 晃 西川 政勝 出口 克巳 白川 茂
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 (ISSN:09157441)
巻号頁・発行日
vol.3, no.6, pp.392-398, 1992-08-01 (Released:2010-08-05)
参考文献数
13
被引用文献数
2 2

The effect of a novel compound, 3-isobutyryl-2-isopropylpyrazolo [1, 5-a] pyridine (ibudilast, KC-404), on human platelet aggregation and its mechanism of action were investigated.In vitro, KC-404 inhibited human platelet aggregation induced by ADP, collagen, adrenalin, platelet activating factor and arachidonic acid but not by ristocetin. Together, KC-404 and agents which increased cAMP (prostaglandin I2, prostaglandin E1 (PGE1), forskolin) or cGMP (3-morpholinosydnonimine (SIN-1)) produced synergistic inhibitory effects on platelet aggregation.KC-404 inhibited human platelet cAMP phosphodiesterase (PDE) (IC50: 50μM) and cGMP-PDE (IC50: 5.2μM) activities. cAMP and cGMP concentration of human platelets were not increased by KC-404 itself. PGE1, an adenylate cyclase stimulator, increased cAMP content; KC-404 enhanced the effect of PGE1 on cAMP accumulation. SIN-1, which stimulates guanylate cyclase, increased cGMP content; KC-404 enhanced the effect of SIN-1 on cGMP accumulation.These results suggest that effects of KC-404 on accumulation of cyclic nucleotides and inhibition of platelet aggregation are mediated via inhibition of platelet cyclic nucleotide phosphodiesterase activities.
著者
中島 茂 東松 豊彦 服部 浩明 岡野 幸雄 野沢 義則
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.17, no.1, pp.59-61, 1986-02-01 (Released:2010-08-05)
参考文献数
10

In many secretory cells, cyclic nucleotides and Ca2+ cooperatively or antagonistically control cell responses. Activation of platelets with thrombin caused a rapid breakdown of phosphoinositides and an increase of cytoplasmic free Ca2+ concentration, which resulted in shape change, secretion and aggregation. The hypothetical concept has recently been proposed that inositol trisphosphate, a degradation product of phosphatidylinositol 4, 5-bisphosphate (PIP2), serves as a second messenger for mobilizing intracellular Ca2+. The effects of cAMP and cGMP on thrombin-induced human pletelet responses were investigated. Thrombin-induced serotonin secretion and aggregation were inhibited by pretreatment with dibutyryl cAMP (dbcAMP) or 8-bromo cGMP (8bcGMP) in a dose-dependent manner. However, shape change was not affected by 8bcGMP. Preincubation of platelets with dbcAMP or 8bcGMP was without effect on the basal level of inositol trisphosphate and free cytosolic Ca2+, measured by fluorescent indicator quin 2, but suppressed their thrombin-induced enhancements. Enhanced [32P] incorporation into phosphatidylinositol 4-phosphate (PIP) and PIP2 was observed with dbcAMP or 8bcGMP treatment, suggesting activation of PI- and PIP-kinases. These results indicate that cGMP as well as cAMP acts as a negative messenger to prevent platelet activation. The inhibitory effect can be explained at least in part by the repression of phospholipase activation, resulting in reduced formation of inositol trisphosphate.
著者
内藤 篤彦
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 (ISSN:09157441)
巻号頁・発行日
vol.26, no.3, pp.297-301, 2015

要約:個体老化とは「加齢に伴い死亡率が増加する原因となる様々な臓器の機能低下」と定義される生命現象である.加齢に伴って免疫系が老化する結果,免疫系本来の非自己を排除する機構と炎症反応を制御する機構が低下し,高齢者で認められる易感染性や慢性炎症が引き起こされる.補体分子C1q は自然免疫系において重要な役割を果たす因子であり,免疫系の老化が引き起こす慢性炎症に伴って血中濃度が増加することが知られているが,われわれはC1q が補体経路非依存性に加齢に伴う骨格筋の再生能低下という老化現象の原因になっていることを報告している.本稿では前半に加齢に伴う免疫系の老化現象について概説し,後半では補体分子C1q による老化誘導のメカニズムについて述べる.
著者
佐藤 敬 高松 滋 作田 茂 水野 成徳 高松 むつ 武田 俊平
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.13, no.3, pp.410-413, 1982-09-01 (Released:2010-08-05)
参考文献数
3

The effects of mefenamic acid on in vitro platelet functions, namely thrombininduced production of thiobarbituric acid-reactive substances (TBARS) and ADP-induced platelet aggregation, were investigated and compared with those of aspirin and flurbiprofen.Mefenamic acid inhibited platelet TBARS production almost comparatively to aspirin and flurbiprofen. The inhibitory effects of these three drugs on platelets from patients with atherosclerotic vascular diseases were smaller than the effects on platelet from normal subjects. Percent inhibition, by mefenamic acid, on platelet TBARS production correlated positively with maximal aggregation in these subjects.Mefenamic acid also strongly suppressed platelet aggregation. In contrast to aspirin and flurbiprofen, of which effects were limited solely on secondary aggregation, mefenamic acid abolished primary aggergation, as well. Therefore, besides being a strong inhibitor of platelet thromboxane generation, mefenamic acid may exert its anti-platelet action through unknown mechanism (s). Antiplatelet action of this drug can be also characterized by the result suggesting that the inhibition tends to be large on platelets with higher aggregatory activity.
著者
八木 高秀 小橋 紀之 香取 瞭
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.18, no.3, pp.250-253, 1987-06-01 (Released:2010-08-05)
参考文献数
8
被引用文献数
1

The purpose of the present study is to clarify the inhibitory mechanism of taurine on platelet aggregation in myocardial infarction. In vitro, platelet aggregations induced by 4.6μM ADP and calcium ionophore in the dose range of 1.7 to 10.0μM A23187 were measured by Born's method with and without 10mM taurine in normal subjects and in cases with old myocardial infarction. Platelet malondialdehyde formation induced by 125μM arachidonic acid was measured by TBA method. In order to estimate the effect of taurine on the change of cytoplasmic Ca2+ in platelet activated by 0.4U/ml thrombin, the intensity of quin 2 fluorescence was measured by Rink's method with and without 10mM taurine.Platelet aggregations induced by 4.6μM ADP and by 2.5 and 5.0μM 23187 were significantly inhibited with 10mM taurine in cases with old myocardial infarction, and also the increase of cytoplasmic Ca2+ in platelet activated by thrombin was significant. In normal subjects, on the other hand, taurine did not inhibit them. In both of cases with old myocardial infarction and normal subjects, platelet malondialdehyde formation was not significantly affected by incubation with 10mM taurine. These results suggest that the inhibitory mechanism of taurine on platelet aggregation is not due to the effect of taurine on arachidonic metabolism, but the inhibition of cytoplasmic Ca2+ change in platelets of the cases with old myocardial infarction.
著者
福田 雅俊
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.6, no.7, pp.557-562, 1975-07-25 (Released:2010-08-05)
参考文献数
8

1 0 0 0 OA 肺血栓塞栓症

著者
長谷川 淳
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 (ISSN:09157441)
巻号頁・発行日
vol.1, no.1, pp.36-40, 1990-02-01 (Released:2010-08-05)
参考文献数
1
著者
吉原 博幸 美原 恒
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.15, no.2, pp.163-166, 1984-04-01 (Released:2010-08-05)
参考文献数
5

The plasma coagulation system was converted to a mathematical model which was described using differential equations. The calculated output patterns of the mathematical model against various input stimulations were compared with results of in vitro assay.The simulated results of (1) Hemophilia A, (2) anticoagulation effect of antithrombin III and (3) anticoagulation effect of heparin corresponded to the results of in vitro assay and clinical reports. However, the simulated result of (4) anticoagulation effect of synthesized arginine derivative No. 805 (MD-805) did not correspond to the results of in vitro assay. Therefore, a new series simulation of MD-805 was done, supposing that MD-805 had an inhibitory activity not only on coagulation factor ha but also VIIa. The new simulation pattern closely resembled the results of in vitro assay. From these facts, it was theoretically indicated that MD-805 also has an inhibitory activity on VIIa.
著者
伊藤 福美 浅井 史敏 木村 努 深見 征治 小林 晋作
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.16, no.2, pp.175-178, 1985-04-01 (Released:2010-08-05)
参考文献数
8

CS-570, a chemically stable prostacyclin derivative, inhibited decrease of platelet counts and fibrinogen level, increase of FDP, prolongation of prothrombin time and activated partial thromboplastin time and deposition of fibrin in the renal glomeruli dose-dependently in the endotoxin-induced DIC model of rats. Ticlopidine, dazoxiben (thromboxane synthetase inhibitor) and BM 13177 (thromboxane antagonist) also showed inhibition of changes in these parameters. CS-570, a potent platelet stabilizer and vasodilator, would probably have inhibited thrombocytopenia and coagulation disorders by physiological antagonism against TxA2 produced by endotoxin. This would suggest beneficial effects of CS-570 in endotoxin-induced DIC in humans.
著者
本田 喬 青崎 正彦 田中 徹 内田 達郎 堀川 良史 石塚 尚子 内山 通子 大木 勝義 田中 直秀 上塚 芳郎 岩出 和徳 金子 昇 木全 心一 関口 守衛 広沢 弘七郎
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.18, no.6, pp.609-614, 1987-12-01 (Released:2010-08-05)
参考文献数
7

We administered tissue-type plasminogen activator (t-PA) intravenously to 10 patients with acute myocardial infarction (AMI) within 6 hours after onset of symptoms, and then examined the state of reperfusion by coronary arteriography (CAG) and observed changes in blood coagulation and fibrinolytic activity to evaluate their effects. AK-124 (by Asahi Chemical Industry and Kowa Co., Ltd. in collaboration), a t-PA produced by tissue culture of normal human lung cells, was given in dosage of 48, 000-576, 000 A. K. units by intravenous infusion over 30-45 minutes. In 7 patients who received t-PA reflow or improved flow was detected on CAG. In t-PA treated patients, euglobulin lysis activity clearly increased, euglobulin lysis time clearly shortened, and D-dimer increased. Levels of circulating fibrinogen and α2-plasmin inhibitor decreased after treatment with t-PA by an average of 12%, 14% of baseline values respectively, but plasminogen showed no detectable change. A hematoma at the site of the catheter insertion was observed in one patient. These observations suggest that t-PA has a higher specificity for fibrin bound plasminogen than for plasminogen and prduces coronary thrombolysis without causing systemic fibrinolysis at least with the present dosage.
著者
小野 百合 三沢 和史 工藤 守 岡崎 裕子 天日 和子 中川 昌一 近藤 光
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
血液と脈管 (ISSN:03869717)
巻号頁・発行日
vol.18, no.4, pp.343-346, 1987

The prevention of diabetic microangiopathy, especially retinopathy, is the last goal of treatment of diabetic patients. Retinopathy is found to progress following rapid control of blood glucose or surgical treatment. To investigate the deterioration of retinopathy, the changes of platelet aggregation induced by ADP, collagen, PAF and epinephrine, of the arachidonate cascade (TXB<sub>2</sub> and 6-keto PGF<sub>1α</sub>), and of blood viscosity were measured during and after surgical treatment or after rapid control of blood glucose. Blood was obtained from 22 diabetics with rapid control of blood glucose and from 11 diabetics undergoing surgical treatment.<br>Platelet aggregation induced by all aggregators was increased after rapid control of blood glucose and after surgical treatment, but decreased during operation. When platelet aggregation before surgical treatment was exaggerated, retinopathy tended to be worsened after surgical treatment. Concerning the arachidonate cascade, both TXB<sub>2</sub> and 6-keto PGF<sub>1α</sub> were increased and the TX/6-keto PGF<sub>1α</sub> ratio was decreased during operation.
著者
山下 勉 香西 かおり 井上 典子 三村 幸一 松岡 瑛
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 (ISSN:09157441)
巻号頁・発行日
vol.3, no.1, pp.49-56, 1992
被引用文献数
2

We have investigated the use of synthetic thrombin inhibitors in assays of thrombin-antithrombin III complexes (TAT). In a purified system, when antithrombin III (AT-III) was incubated with thrombin, a complex of 90KD was formed gradually during the first 60 minutes and this complex was converted to lower molecular weight species (78-86×10<sup>3</sup>) within 48 hours. Additionally, the interaction of thrombin and AT-III was studied in the presence of heparin. A 93KD complex was formed immediately and then lower molecular weight complexes (78-86×10<sup>3</sup>) were formed during 60 minutes of incubation. In these circumstances, therefore, heparin seemed to accelerate the breakdown of TAT complexes. Plasma values of TAT were measured by ELISA in the presence of heparin and were reduced by approximately 55per cent during 48 hours of incubation. These findings suggested that the biochemical nature of TAT was modified during incubation, and that the assays for TAT in plasma might not detect lower molecular weight forms of the complex. However, a synthetic thrombin inhibitor, argatroban (0.1mM/<i>l</i>) prevented these changes. The levels of TAT in plasma were increased by adding tissue factor or contact factor activator to the assay mixture. Argatroban (0.01mM/<i>l</i>) or another synthetic protease inhibitor, FOY (4.3mM/<i>l</i>), inhibited this generation of TAT. These observations suggested that argatroban minimized the changes of TAT molecular weight and prevented generation of TAT <i>in vitro</i>. The data indicated that the addition of argatroban (final concentration 0.1mM/<i>l</i>) to plasma would permit more accurate measurements of circulating levels of TAT.
著者
水口 純 副島 見事 岩永 貞昭
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis (ISSN:09157441)
巻号頁・発行日
vol.15, no.2, pp.94-106, 2004-04-01
被引用文献数
2 1

凝固カスケードを構成する一群のビタミンK依存性セリンプロテアーゼのVII因子やIX因子,X因子,プロテインCは,互いに似た3次元立体構造を示すが,その基質特異性や触媒活性はそれぞれ特有である.近年,これらの因子について,従来の分子異常の報告に加え,3次構造の解析,遺伝子欠損マウスや,ヒト以外の各種動物でのアミノ酸配列の報告,活性を増減させた改変体の作出などの研究が急速に進んだ.<br>その結果,これらの因子の構造と機能に関する新たな知見が質・量ともに増し,巨視的には似た構造である各因子の,どの領域がそれぞれの特徴を担っているかが解明されつつある.中でもVII因子は,組織因子とともに外因系凝固カスケードの開始点に位置し,その特性として,単に特異的切断を受けただけでは触媒活性はほとんど無く,組織因子と結合して初めて生理学的な活性を発現するというユニークさを持つ.これは生体にとって有害である無秩序な血液凝固を防ぐために,自然が紡ぎ出した巧妙なメカニズムと言えよう.では,この精妙な機構を司るのはVII因子のどの領域であり,他の因子と比較してどの様な差があるのであろうか? 本稿(前編+後編)では,特にVII因子の3次構造を中心としたここ数年の知見に,我われのデータもまじえつつ解説したい(VIIの最近の代表的な総説を文献リストの最初に示す<SUP>1)-6)</SUP>.また,文献は後編にまとめて記載する.).
著者
藤井 輝久 高田 昇 日笠 聡 酒井 道生 竹谷 英之 櫻井 嘉彦 花房 秀次 小阪 嘉之 天野 景裕 嶋 緑倫 吉岡 章
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis (ISSN:09157441)
巻号頁・発行日
vol.17, no.4, pp.446-453, 2006-08-01
被引用文献数
1

8施設の血友病患者の入院医療コストを集計し, その特徴と診断群分類(DPC)点数表の導入に対する問題点を考察した. 2002年4月から2004年3月までの8施設における患者の各入院に対し, 血友病の種類, 体重, インヒビターの有無, 手術の有無, 入院日数, 請求点数などを集計した. さらにそれらのデータからそれぞれの因子により請求点数を解析し, どの因子が請求点数に関与しているか統計学的検定を行った. 入院日数, 請求点数は施設間にばらつきがみられ, 施設別1日あたりの平均医療コストは最少が124,110円, 最大が222,080円であった. 体重別では25kg未満127,280円, 25-50kg 210,720円, 50-75kg 280,861円, 75kg以上526,958円で有意差がみられた. インヒビターの有無(524,416円, 147,534円)でも有意差がみられた. 2004年度の血友病類縁疾患のDPC導入案と比較すると, 全施設で病院側の赤字になることが分かった. 以上より, 血友病患者の入院医療コストは患者の体重や状態により多種多様で, 安易にDPCを導入することは問題と思われた.
著者
嶋 緑倫 田中 一郎 川合 陽子 辻 肇 中村 伸 森田 隆司
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis (ISSN:09157441)
巻号頁・発行日
vol.14, no.2, pp.107-121, 2003-04-01
参考文献数
19
被引用文献数
36 22

後天性インヒビターによる出血症状は, 一般に強く, 難治性で治療に苦慮する症例も多い. 近年, 凝固検査の普及により報告例が増加しつつあるが, わが国における後天性インヒビターの実態は不明であり, 治療法も標準化されていない. そこで, 日本血栓止血学会学術検討部会凝固委員会(森田隆司委員長)が実態調査を行った. 方法は日本血栓止血学会会員を中心に1次アンケートを依頼し, 後天性インヒビターの症例を有するとの返答のあった施設に対して2次アンケート調査を依頼した(調査期間:平成13年1月より平成14年5月31日). 計75症例の後天性インヒビターの報告があった. 内訳は, 抗第VIII因子インヒビター58例, 抗von Willebrand因子インヒビター7例, 抗第V因子インヒビター5例, 抗プロトロンビンインヒビター1例, 抗XI因子インヒビター1例, 抗フィブリノゲンインヒビター1例, 抗第VIII因子+第V因子+フィブリノゲン複合インヒビター1例, 抗第VIII因子+第IX因子複合インヒビター1例であった. 男女比は <B>41</B>:34, 発症年齢の範囲は2~80歳でピークは70歳台であった. 基礎疾患のある例とない例との比は <B>29</B>:46であった. 基礎疾患や臨床背景で多かったのは自己免疫性疾患, リンパ増殖性疾患や腫瘍, 妊娠, 分娩, 糖尿病などであった. 止血療法で抗第VIII因子インヒビター例では, 第VIII因子製剤22例が最も多く使用されていたが, 有効率は低く, 活性型第VII因子製剤や(A)PCC製剤などによるバイパス療法の有効率が高かった. 免疫抑制療法としてはステロイドの内服投与が最も多かった. 有効率は約60%で, 他の免疫抑制剤も同様であった. 転帰はインヒビター消失例37例, 低下例14例, 不変例8例で, 死亡率は15%であった.

1 0 0 0 血小板製剤

著者
半田 誠
出版者
The Japanese Society on Thrombosis and Hemostasis
雑誌
日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis (ISSN:09157441)
巻号頁・発行日
vol.20, no.5, pp.495-497, 2009-10-01
被引用文献数
1 5

Points<br>(1) 血小板輸血の目的は,血小板の量的,質的低下に基づいた出血の予防(予防的投与)や治療(治療的投与)である.<br>(2) 輸血に用いる血小板濃厚液は,厳密な保存条件で,使用期限はわずかに4日間である.<br>(3) 輸血の適応は,1)血小板数のみではなく,2)出血症状(出血スコア)や3)成因や合併症,侵襲的処置の有無等の出血リスクを勘案して,総合的に判断する.<br>(4) 白血病等の造血器疾患や化学療法に伴う造血障害での予防的投与(内科的予防投与)の血小板基準値(トリガー値)は1~2 万/μl である.<br>(5) 外科手術時の過剰出血の予防(外科的予防投与)や活動性の出血の治療(治療的投与)では,血小板数5 万/μl 以上を目標に輸血する.<br>(6) 標準は10 単位製剤で,輸血で3~5 万/μl 血小板数の増加が期待され,基準値を維持するには造血停止状態では週2~3 回の輸血が必要である.<br>(7) 輸血翌日の血小板数を測定して,効果判定を習慣づけ,輸血不応があった場合は,その原因を検討して,対応する.