<ORIGINAL ARTICLE>Characterization of a new coagulant enzyme isolated from Trimeresurus okinavensis (Himehabu snake) venom

A potent, proteinaceous inducer of coagulation factors, has been purified to homogeneity from Trimeresurus okinavensis (Himehabu snake) by ion exchange chromatography and molecular sieving. It has an apparent molecular weight of 28,000 and it specifically converts fibrinogen to fibrin through an enzymatic reaction. This activity was confirmed by a method using synthetic substrate S-2238, though the fraction from a DEAE sephacel column chromatography shows amidolytic activity of S-2251 and S-2366, which are commonly used to measure plasmin and activated protein C activity, respectively, as well as S-2238. This thrombin-like activity of the final product was not affect by the addition of heparin and AT-III. This enzyme also aggregates normal platelets. It is considered that this purified enzyme would be useful as a hemostatic agent or research reagent

Considerations for simultaneous detection of autoantibodies to coagulation factor and lupus anticoagulant

In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in LA cases; therefore, immunological confirmation of antibodies against coagulation factors is recommended. Additionally, acquired hemophilia A (AHA), caused by autoantibodies against FVIII, is a typical acquired hemorrhagic diathesis, although affected patients may present with thrombosis associated with LA. Thus, it is important to remember that hemorrhagic diathesis due to autoantibodies against clotting factors can also result in thrombosis, as demonstrated by the co-detection of LA. When clotting factor inhibitors are detected in LA-positive individuals, it is important to confirm the presence of autoantibodies against coagulation factors using immunological methods, such as ELISA, to avoid false-positive results

Non-traumatic myositis ossificans mimicking a malignant neoplasm in an 83-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myositis ossificans is a benign, self-limiting condition that usually affects young, athletically active men. To the best of our knowledge, this case report describes the oldest recorded patient with myositis ossificans.</p> <p>Case presentation</p> <p>Our patient was an 83-year-old Japanese woman who presented with a one week history of a palpable mass in the left thigh. She had a history of surgery for transverse colon cancer and lung cancer at the ages of 73 and 80, respectively. Clinical and radiological examinations suggested a malignant neoplasm such as metastatic carcinoma or extraskeletal osteosarcoma. A diagnosis of myositis ossificans was made by core needle biopsy. Our patient was asymptomatic and had no recurrence at one year follow-up.</p> <p>Conclusion</p> <p>Clinicians should consider myositis ossificans as a possible diagnosis for a soft tissue mass in the limb of an older patient, thereby avoiding unnecessarily aggressive therapy.</p

Reciprocal influence of the p53 and the hypoxic pathways

When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilised by cellular stresses and which has a major role in the cell responses to these stresses. The aim of this review is to compile what has been reported until now about the interconnection between these two important pathways. Indeed, according to the cell line, the severity and the duration of hypoxia, oxygen deficiency influences very differently p53 protein level and activity. Conversely, p53 is also described to affect HIF-1α stability, one of the two subunits of HIF-1, and HIF-1 activity. The direct and indirect interactions between HIF-1α and p53 are described as well as the involvement in this complex network of their respective ubiquitin ligases von Hippel Lindau protein and murine double minute 2. Finally, the synergistic or antagonistic effects of p53 and HIF-1 on some important cellular pathways are discussed

ループスアンチコアグラント検査におけるクロスミキシング試験の標準化に関する研究

クロスミキシング試験(CMT)における種々の活性化部分トロンボプラスチン時間(APTT)試薬とさまざまな凍結乾燥市販正常血漿の有用性および判定方法について検討した。APTT-LA測定に有用なAPTT試薬の検討では、ループスアンチコアグラント(LA)検査が陽性の患者21例の血漿を用い、健常人50名を対照群とした。測定値の比較ではPTT-LAと最も近似した測定値を示したのはAPTT-3であり、最も乖離したのはAPTT-5であった。日本血栓止血学会標準化委員会(JSTH-SSC)がLA試薬として推奨するPTT-LAとの相関性はAPTT-4が相関係数r=0.883と最も高く、次いでAPTT-3が良好であった。また、LA検査としてCMTに用いるコントロール血漿の検討では、凝固スクリーニング検査の結果はいずれのコントロール血漿も正常域であったが、APTT値においてGeorge King NORMAL PLASMAとPOOL NORM(RD)は他の正常血漿に比較してやや延長していた。内因系凝固因子活性はRDが他のコントロール血漿と比較して第VIII因子および第IX因子、第XII因子活性が低下していた。特に、第IX因子および第XII因子活性値はそれぞれ基準値以下であった。博士（医学）旭川医科大

Increase in plasma thrombin-activatable fibrinolysis inhibitor may not contribute to thrombotic tendency in antiphospholipid syndrome because of inhibitory potential of antiphospholipid antibodies toward TAFI activation

Background: The causes of thrombosis in antiphospholipid syndrome (APS) remain unknown, though several hypotheses in regard to hypofibrinolysis have been proposed. Objective: To clarify the mechanism, we measured plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) in APS patients. Methods and Results: Both the TAFI antigen (TAFI:Ag) level measured with an ELISA, and thrombin-thrombomodulin-dependent TAFI activity (TAFI:Ac) were elevated in 68 APS patients as compared with those in 66 healthy controls, though they were lower than those in 46 patients with autoimmune diseases. As for the influence of antiphospholipid antibodies (aPL) on TAFI levels, the mean TAFI:Ac level in 39 SLE patients positive for APS was significantly lower than that in 27 SLE patients without APS, whereas there was no difference in TAFI:Ag between those groups. Furthermore, purified IgG from patients positive for aPL, and monoclonal aPL (EY2C9 and 23-1D) inhibited the activation of TAFI in a concentration dependent manner. Conclusion: These results suggest that aPL inhibits TAFI activation by affecting the function of thrombomodulin-thrombin complex through phospholipids. Although TAFI in plasma is elevated in autoimmune diseases including APS, we concluded that an elevated level is not likely a risk factor for thrombosis in APS patients, because of the inhibition of TAFI activation by aPL

Involvement of 5-HT2A receptor hyperfunction in the anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment in rats

We examined whether combination treatment with doxorubicin and cyclophosphamide, a traditional chemotherapy for breast cancer, induced anxiety-like behavior in rats. Furthermore, we evaluated the role of the serotonin (5-HT)2A receptor subtype in the anxiety-like behavior induced by such chemotherapy. Rats were intraperitoneally injected with doxorubicin and cyclophosphamide once a week for 2 weeks. This caused the rats to display anxiety-like behavior during the light–dark test. In addition, we examined the rats' 5-HT2A receptor-mediated behavioral responses. Combination treatment with doxorubicin and cyclophosphamide significantly increased (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, (a 5-HT2A receptor agonist)-induced wet-dog shake activity. This anxiety-like behavior was significantly inhibited by mirtazapine, a 5-HT2A receptor antagonist/5-HT1A receptor agonist, and tandospirone, a partial 5-HT1A receptor agonist, but not by fluoxetine, a selective serotonin reuptake inhibitor. The anxiety-like behavior induced by doxorubicin and cyclophosphamide combination treatment is mediated by hyperfunctioning of the 5-HT2A receptor. Thus, 5-HT2A receptor antagonists or 5-HT1A receptor agonists might be useful for treating chemotherapy-induced anxiety disorders. Keywords: Doxorubicin, Cyclophosphamide, 5-HT2A receptor, Anxiet