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Koji Habe,
Hideo Wada, Takeshi Matsumoto,
Kohshi Ohishi,
Makoto Ikejiri,
Kimiko Matsubara,
Tatsuhiko Morioka,
Yuki Kamimoto,
Tomoaki Ikeda,
Naoyuki Katayama,
Tsutomu Nobori,
Hitoshi Mizutani
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ABSTRACT: Antiphospholipid antibodies (aPL) including lupus anticoagulant (LA), anticardiolipin antibodies (aCL) IgG and aCL-β2-glycoprotein I (β2GPI) complex IG are causative factors for thrombotic event (THE). We retrospectively investigated relationships between aPLs and THE in 458 patients suspected of having antiphospholipid syndrome. THEs were observed in 232 of 458 patients, including 148 cases of venous thrombosis, 59 of arterial thrombosis, 18 of microthrombosis, and 20 of complications of pregnancy. The frequency of THE was significantly high in patients positive for LA and/or aPL. In patients with autoimmune disease (AID), the frequency of THE was significantly high in patients with any types of aPLs. Additionally, risk of THE was significantly increased in patients with more than two types of aPLs. Prolonged activated partial thromboplastin time indicated a high risk for THE. However, neither thrombocytopenia nor AID was a risk for THE. In conclusion, the presence of aPL is an indicator for high risk of THE in patients in whom THE was suspected. However, the risk of THE in aPL-positive patients varied among patients with different underlying diseases.
International journal of hematology 02/2013; · 1.17 Impact Factor
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ABSTRACT: INTRODUCTION: Thrombotic microangiopathy (TMA) is one of the important complications occurring after liver transplantation (LT), and it is suggested that a Von Willebrand factor (VWF) and ADAMTS13 may play an important role in the onset of TMA and poor outcome after LT. MATERIALS AND METHODS: In 81 patients after living donor LT (LDLT), 17 patients who had both severe thrombocytopenia and hemolytic anemia with fragmented red cell were diagnosed as TMA- like syndrome (TMALS) and 10 patients died. RESULTS: ADAMTS13 activities were slightly low, and plasma levels of VWF and VWF propeptide (VWFpp) antigens and the ratio of VWFpp/VWF were significantly high before LDLT. ADAMTS13 activities were significantly reduced from day 1 to day 28 after surgery, and plasma levels of VWF antigen slightly decreased on day 1 and plasma levels of VWFpp continued to be high. The ratio of VWFpp/VWF was significantly high on day 1 after surgery. The mortality was high in the patients with TMALS and the frequency of TMALS was high in non-survivors. VWF levels were significantly low and the ratio of VWFpp/VWF was significantly high in those with TMALS on day 1 after surgery. The ADAMTS13 activity was significantly low, and the VWFpp and the VWFpp/ADAMTS13 ratio were significantly high in non-survivor on day 28 after surgery. CONCLUSION: These findings suggest that VWF and ADAMTS13 might therefore play an important role in the onset of TMA and poor outcome after LT. The VWFpp may therefore be a more useful marker for the diagnosis of TMALS than VWF.
Thrombosis Research 12/2012; · 2.44 Impact Factor
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Bing Liu,
Kohshi Ohishi,
Yuki Orito,
Yoshiki Nakamori,
Hiroyoshi Nishikawa,
Kazuko Ino,
Kei Suzuki, Takeshi Matsumoto,
Masahiro Masuya,
Hirofumi Hamada,
Junichi Mineno,
Ryoichi Ono,
Tetsuya Nosaka,
Hiroshi Shiku,
Naoyuki Katayama
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ABSTRACT: T cell precursors are an attractive target for adoptive immunotherapy. Here, we examined regulation of human early T lymphopoiesis by human bone marrow stromal cells to explore in vitro manipulation of human T cell precursors in a human-only coculture system. Generation of CD7(+)CD56(-)cyCD3(-) proT cells from human hematopoietic progenitors on telomerized human bone marrow stromal cells was enhanced by stem cell factor (SCF), flt3 ligand (Flt3L) and thrombopoietin (TPO), but these stimulatory effects were suppressed by interleukin-3. Expression of Notch ligands Delta-1 and -4 on stromal cells additively promoted T cell differentiation into the CD7(+)cyCD3(+)preT cell stage, while cell growth was strongly inhibited. By combining these coculture systems, we found that initial coculture with telomerized stromal cells in the presence of SCF, Flt3L and TPO, followed by coculture on Delta-1- and -4-coexpressing stromal cells led to a higher percentage and number of preT cells. Adoptive immunotherapy using peripheral blood T cells transduced with a tumor antigen-specific T cell receptor (TCR) is a promising strategy but has several limitations such as the risk of forming a chimeric TCR with the endogenous TCR. We demonstrated that incubation of TCR-transduced hematopoietic progenitors with the combination of coculture systems gave rise to CD7(+)TCR(+)CD3(+)CD1a(-) T cell precursors that rapidly proliferated and differentiated under the culture condition to induce mature T cell differentiation. These data show the regulatory mechanism of early T lymphopoiesis on human stromal cells and the potential utility of engineered human stromal cells to manipulate early T cell development for clinical application.
Experimental hematology 12/2012; · 3.11 Impact Factor
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Yoshiki Nakamori,
Bing Liu,
Kohshi Ohishi,
Kei Suzuki,
Kazuko Ino, Takeshi Matsumoto,
Masahiro Masuya,
Hiroyoshi Nishikawa,
Hiroshi Shiku,
Hirofumi Hamada,
Naoyuki Katayama
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ABSTRACT: The regulation of human early lymphopoiesis remains unclear. B- and T-lineage cells cannot develop simultaneously with conventional stromal cultures. Here we show that telomerized human bone marrow stromal cells supported simultaneous generation of CD19(+) CD34(lo/-) CD10(+) cyCD79a(+) CD20(+/-) VpreB(-) pro-B cells and CD7(+) CD34(+) CD45RA(+) CD56(-) cyCD3(-) early T/Natural Killer (NK) cell precursors from human haematopoietic progenitors, and the generation of both lymphoid precursors was promoted by flt3 ligand (flt3L). On the other hand, stem cell factor or thrombopoietin had little or no effect when used alone. However, both acted synergistically with flt3L to augment the generation of both lymphoid precursors. Characteristics of these lymphoid precursors were evaluated by gene expression profiles, rearrangements of IgH genes, or replating assays. Similar findings were observed with primary human bone marrow stromal cells. Notably, these two lymphoid-lineage precursors were generated without direct contact with stromal cells, indicating that early B and T/NK development can occur, at least in part, by stromal cell-derived humoral factors. In serum-free cultures, flt3L elicited similar effects and appeared particularly important for B cell development. The findings of this study identified the potential of human bone marrow stromal cells to support human early B and T lymphopoiesis and a principal role for flt3L during early lymphopoiesis.
British Journal of Haematology 03/2012; 157(6):674-86. · 4.94 Impact Factor
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Kakunoshin Yoshida,
Hideo Wada,
Masahiro Hasegawa,
Hiroki Wakabayashi, Takeshi Matsumoto,
Yuji Shimokariya,
Katsura Noma,
Norikazu Yamada,
Atsumasa Uchida,
Tsutomu Nobori,
Akihiro Sudo
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ABSTRACT: We evaluated hemostatic markers in patients who underwent major orthopedic surgery, including total hip and total knee arthroplasty, and were treated for the prophylaxis of deep vein thrombosis (DVT) with or without fondaparinux (anti-Xa group, n = 98 and without anti-Xa group, n = 20). The frequency of DVT was significantly higher in the without anti-Xa group than in the anti-Xa group, but the reduction of hemoglobin and fibrinolytic marker levels was significantly lower in the without anti-Xa group than in the anti-Xa group. Eighteen patients in the anti-Xa group showed a reduction in hemoglobin of more than 2 g/dl, and those individuals were considered to be the increased bleeding (IB) group. The concentration of fibrinolytic markers in the anti-Xa group was significantly higher in the IB group than in the non-IB group. There were also no significant differences in the levels of anti-Xa activity, plasminogen activator inhibitor-I, soluble fibrin and antithrombin between the IB and non-IB groups. In conclusion, elevated fibrinolysis induced by increased bleeding may lead to further increases in bleeding in patients receiving thromboprophylaxis with fondaparinux following major orthopedic surgery.
International journal of hematology 02/2012; 95(2):160-6. · 1.17 Impact Factor
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ABSTRACT: Thrombophilia is frequently associated with venous thromboembolism (VTE) including cerebral venous sinus thrombosis (CVST). The possibility of thrombophilia was examined in 12 patients with CSVT diagnosed in the past 9 years. Thrombophilia due to abnormalities in antithrombin (AT), protein C (PC), or protein S (PS) or antiphospholipid syndrome (APS) was evaluated. Nine patients with abnormally decreased AT, PC or PS and one patient with APS were examined. Of the nine patients examined by a gene analysis of AT, PC, or PS, one had a congenital AT deficiency, one had a congenital PC deficiency, and two had congenital PS deficiencies including a novel mutant (Gly189Ala). AT, PC and PS levels were all decreased in one patient, PS level was decreased in three patients, and AT level was decreased in one patient at the onset of CVST, but these concentrations improved after treatment. CVST is frequently associated with thrombophilia and a transient decrease in AT, PC or PS may be a causal factor.
International journal of hematology 01/2012; 95(3):257-62. · 1.17 Impact Factor
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ABSTRACT: ADAMTS13, endothelial von Willebrand factor (VWF) and related proteins are involved in the pathogenesis of some life threatening systemic thrombotic coagulopathies. Changes of plasma ADAMTS13 activity in thrombotic thrombocytopenic purpura (TTP) is well known but is also involved in septic disseminated intravascular coagulation (DIC). Here we investigated the ADAMTS13 activity, VWF and VWF propeptide (VWFpp) antigens in 69 patients with DIC, 143 with non-DIC, 21 with thrombotic thrombocytopenic purpura (TTP) and 23 with atypical hemolytic uremic syndrome (aHUS) for diagnosis of DIC. The plasma ADAMTS13 activity was significantly low in patients with DIC, and the plasma levels of VWF and VWFpp antigens, were the highest in these patients, but there were no significant differences in the plasma VWFpp levels between the patients with DIC and those with aHUS. The difference in the plasma ADAMTS13 activity, the VWF and VWFpp antigens between DIC and non-DIC cases was significant in those with infectious and malignant diseases, but the difference in the VWFpp/ VWF ratio were significant only in subjects with infectious diseases. As an indicator for prognosis, the plasma levels of VWFpp were significantly higher in non-survivors than in survivors. Then, VWFpp/ VWF ratio and VWFpp/ADAMATS13 ratio will be potent informative indicators in DIC. These findings suggest that ADAMTS13/VWF profiles may have important roles in the pathogenesis of DIC, and that ADAMTS13 and VWFpp are useful indicators for the diagnosis and prognosis of DIC.
Thrombosis Research 11/2011; 129(5):598-602. · 2.44 Impact Factor
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Kakunoshin Yoshida,
Hideo Wada,
Masahiro Hasegawa,
Hiroki Wakabayashi,
Honami Ando,
Seika Oshima, Takeshi Matsumoto,
Yuji Shimokariya,
Katsura Noma,
Norikazu Yamada,
Atsumasa Uchida,
Tsutomu Nobori,
Akihiro Sudo
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ABSTRACT: The efficacy of measuring anti-Xa activity was evaluated in major orthopedic surgery patients receiving thrombo-prophylaxis with Fondaparinux. Although 98 orthopedic patients including those receiving total hip replacement (THR) and total knee replacement (TKR) were treated with 1.5 mg of Fondaparinux for prophylaxis of deep vein thrombosis (DVT). Sixteen patients developed DVT, but none was associated with a fatal pulmonary embolism. There was a wide range of anti-Xa activity, but there were no patients with less than 0.15 mg/l or more than 0.90 mg/l. Anti-Xa activity gradually increased from days 1 to 8 and showed no significant difference between patients with and without DVT. Anti-Xa activity was correlated with weight, height, body mass index, and antithrombin activity. Postoperative plasma levels of D: -dimer and soluble fibrin (SF) were markedly high, and those were significantly reduced at days 1 and 4 of treatment with Fondaparinux. Plasma levels of SF were significantly reduced at days 8 and 15, but D: -dimer was not. These findings suggested that there was continued thrombin generation after the injection of Fondaparinux until day 8 and secondary fibrinolysis occurred on day 8. In conclusion, 1.5 mg of Fondaparinux may not be sufficient for the prophylaxis of silent DVT, but it was found to be useful for that of fatal pulmonary embolism. Consequently, monitoring anti-Xa activity may be unnecessary for the administration of Fondaparinux at such doses.
International journal of hematology 09/2011; 94(4):355-60. · 1.17 Impact Factor
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Rinsho byori. The Japanese journal of clinical pathology 02/2011; Suppl 147:111-6.
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Naomi Ito-Habe,
Hideo Wada, Takeshi Matsumoto,
Kohshi Ohishi,
Hidemi Toyoda,
Eiji Ishikawa,
Shinsuke Nomura,
Yoshihiro Komada,
Masaaki Ito,
Tsutomu Nobori,
Naoyuki Katayama
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ABSTRACT: Thrombotic microangiopathy (TMA) is associated with vascular endothelial cell injury and is sometimes linked with poor outcome. Von Willebrand factor (VWF) propeptide (VWFpp) is considered to be a marker of vascular endothelial cell injury. The plasma levels of VWF, VWFpp, and thrombomodulin (TM) were evaluated for their use in the diagnosis of TMA in 75 patients with TMA. There were 30 TMA patients with marked decreases in ADAMTS13 (TMA/ADAMTS13) and 45 without the decrease (TMA/other). The plasma levels of TM, VWF, and VWFpp values were significantly high in patients with TMA, especially TMA/other group. The plasma levels of TM and VWFpp were significantly high in non-survivor with TMA. In the TMA/other group, the plasma levels of VWFpp were negatively correlated with ADAMTS13 activity. The plasma levels of TM correlated with the renal function, but the plasma levels of VWFpp did not. A ROC analysis indicated that VWFpp and TM were useful markers for the prediction of a poor outcome. These findings suggest that VWFpp is an useful marker for the diagnosis of TMA and for the prediction of poor outcome.
International journal of hematology 01/2011; 93(1):47-52. · 1.17 Impact Factor
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ABSTRACT: A 30-year-old Brazilian man hospitalized with AIDS developed a high-grade fever. Neither culture studies nor radiological examinations revealed the cause; small yet highly intense signals in the basal ganglia were detected upon gadolinium (Gd)-enhanced T1-weighted magnetic resonance imaging (MRI) of the head. This finding was equivocal at that time but obviously abnormal for his age. A week later, he developed a movement disorder in his right arm, speech apraxia, and a worsening disturbance of consciousness. Repeated Gd-enhanced T1-weighted MRI demonstrated incredible changes in the brain; enhanced lesions in the basal ganglia deteriorated over time, multiple nodular and ring-enhanced lesions were observed in almost the entire brain. A diagnosis of toxoplasma encephalitis (TE) was confirmed by the detection of Toxoplasma gondii DNA in the cerebrospinal fluid. After initiation of intravenous trimethoprim-sulfamethoxazole (TMP-SMX; 10 mg/kg/day of TMP and 50 mg/kg/day of SMX) treatment, his symptoms and radiological findings improved dramatically. Our case suggests that high-intensity signals seen in the basal ganglia of a Gd-enhanced T1-weighted MRI, even at the preclinical stage, is indicative of TE. Because the use of MRI in general has become more widespread, it is predicted that preclinical lesions of TE will be found in various clinical settings more frequently.
Journal of Infection and Chemotherapy 04/2010; 16(2):135-8. · 1.80 Impact Factor
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Makoto Ikejiri,
Akihiro Tsuji,
Hideo Wada,
Yuko Sakamoto,
Junji Nishioka,
Satoshi Ota,
Norikazu Yamada, Takeshi Matsumoto,
Kaname Nakatani,
Tsutomu Nobori,
Masaki Itoh
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ABSTRACT: A protein S (PS) abnormality is a hereditary risk factor for thromboembolism. A 33-year-old female had a left deep vein thrombosis (DVT) and mild pulmonary embolism (PE). Her PS antigen level was 34.7% and the activity level was less than 10%. Genetic analysis identified three missense mutations in PS: the D38Y mutation in exon 3, and the T589I mutation and P626L mutations in exon 15. The D38Y mutation has not been reported previously. An analysis of the patient's family revealed that all members of the family had some PS gene mutation. The D38Y and T589I mutations were both in same allele, the P626L mutation was in another allele. The expression of PS mutations in COS-7 cells revealed that PS activity and antigen were markedly decreased in the D38Y mutation but not in the T589I mutation. The expression of the P626L mutation in baby hamster kidney (BHK) cells showed the PS activity and antigen to be markedly decreased in comparison to the wild type.
Thrombosis Research 02/2010; 125(6):529-32. · 2.44 Impact Factor
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Toshihiko Kobayashi,
Hideo Wada,
Masanobu Usui,
Hiroyuki Sakurai, Takeshi Matsumoto,
Tsutomu Nobori,
Naoyuki Katayama,
Sinji Uemoto,
Hiromichi Ishizashi,
Masanori Matsumoto,
Yoshihiro Fujimura,
Shuji Isaji
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ABSTRACT: Thrombotic microangiopathy (TMA) is a complication occurring after liver transplantation (LT), and an unusually large multimer (ULM) of Von Willebrand factor (VWF) and ADAMTS13 may play an important role in the onset of TMA during LT.
Eight-one patients underwent living donor LT (LDLT). Seventeen of those patients had both severe thrombocytopenia and hemolytic anemia with fragmented red cells and were diagnosed as TMA- like syndrome (TMALS).
A significant reduction of ADAMTS13 and an increase of VWF were observed in the patients with TMALS. The ADAMTS13 activity in patients after LDLT was significantly reduced from day 1 to day 21, and it was significantly low in those with TMALS at day 14 and 28. The VWF levels in patients with LDLT were significantly high, and the VWF/ADAMTS13 ratio was significantly increased in patients at 7, 14 and 28 days after LDLT, especially in patients with TMALS at day 14 and 28 after LDLT. High molecular weight multimers of VWF were observed to have increased in patients with LDLT, and the high molecular weight multimers of VWF were further increased in those with mild TMALS but they decreased in those with severe TMA. These findings suggest that ULM- VWF and ADAMTS13 might be associated with the onset of TMA after LT.
Thrombosis Research 06/2009; 124(5):541-5. · 2.44 Impact Factor
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Akihiro Tsuji,
Hideo Wada, Takeshi Matsumoto,
Yasunori Abe,
Satoshi Ota,
Norikazu Yamada,
Takashi Sugiyama,
Akihiro Sudo,
Katsuya Onishi,
Kaname Nakatani,
Atsumasa Uchida,
Masaaki Ito,
Koji Suzuki,
Tsutomu Nobori
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ABSTRACT: The fibrin-related markers (FRMs), including soluble fibrin (SF), D-dimer and fibrin and fibrinogen degradation products (FDP) are considered to be useful for the diagnosis of thrombosis; however, evidence for the diagnosis of thrombosis by SF is still not well established. The present study was designed to evaluate the usefulness of SF in the diagnosis of venous thromboembolism (VTE). The plasma concentrations of FRMs were measured in 551 in-patients suspected to have a VTE. The plasma levels of SF, D-dimer and FDP were significantly higher in patients with VTE than patients without VTE and those were significantly higher in patients without VTE than in healthy volunteers. In a receiver operating characteristic analysis for the diagnosis of VTE, the area under the curve was 0.950 for SF, 0.933 for FDP and 0.805 for D-dimer. The appropriate cut-off values for the diagnosis were as follows SF 5.9 microg/ml, FDP 2.1 microg/ml and D-dimer 4.8 microg/ml. To obtain a 100% negative predictive value for the diagnosis of VTE, the SF was less than 5.2 microg/ml, FDP was less than 1.3 microg/ml, and D-dimer was less than 0.5 microg/ml. Our findings suggest that the SF assay is useful for the diagnosis and exclusion of VTE.
International journal of hematology 11/2008; 88(4):448-53. · 1.17 Impact Factor
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Yasunori Abe,
Hideo Wada,
Eri Yamada,
Maki Noda,
Makoto Ikejiri,
Junji Nishioka,
Toshihiko Kobayashi, Takeshi Matsumoto,
Masahiro Masuya,
Syuji Isaji,
Masanobu Usui,
Sinji Uemoto,
Naoyuki Katayama,
Tsutomu Nobori
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ABSTRACT: Thrombotic microangiopathy (TMA) or thrombotic thrombocytopenic purpura (TTP) is a life-threatening syndrome characterized by increased number of fragmented red cells (FRCs) and thrombocytopenia. FRCs can be measured using the recently developed automated hematology analyzer XE-2100. The normal range for FRCs is 0% to 0.205%, as determined by the automated hematology analyzer XE-2100. The FRC count is significantly elevated in patients with TMA associated with liver transplantation, bone marrow transplantation, or TTP. In patients with TMA after liver transplantation, the FRC count is significantly higher than in those without TMA. In receiver operating characteristic analysis for the diagnosis of TMA, the area under the curve is 0.986, suggesting that FRC is a useful marker for the diagnosis of TMA. When the cutoff value of FRC for TMA is 1.2%, the sensitivity is 90% and the specificity is 96%, indicating that FRC is the most useful screening test for the diagnosis of TMA.
Clinical and Applied Thrombosis/Hemostasis 08/2008; 15(3):257-62. · 1.33 Impact Factor
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Takeshi Matsumoto,
Toshihiro Kaneko,
Masashi Seto,
Hideo Wada,
Toshihiko Kobayashi,
Kaname Nakatani,
Harue Tonomura,
Yasutaka Tono,
Mariko Ohyabu,
Tsutomu Nobori,
Hiroshi Shiku,
Akihiro Sudo,
Atsumasa Uchida,
Deborah J Stearns Kurosawa,
Shinichiro Kurosawa
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ABSTRACT: Proteinase 3 (PR3) expression on neutrophils was examined in rheumatoid arthritis (RA) patients before and after antitumor necrosis factor (TNF)-alpha therapy. Membrane PR3 expression from patients with either an infection or RA significantly increased. Membrane PR3 expression on neutrophils from RA patients treated with infliximab (anti-TNF-alpha antibody) therapy was less than in those without such treatment in a resting state, but the expression later increased after stimulation in vitro. Membrane PR3 expression increased because of the stimulation of TNFalpha, whereas it was significantly suppressed by plasma or alpha(1)-proteinase inhibitor. The condition of patients with RA improved after treatment with infliximab. Membrane PR3 expression on neutrophils in RA patients was downregulated by infliximab. As a result, PR3 might play an important role in the neutrophil-mediated inflammatory reaction in patients with either RA or an infection.
Clinical and Applied Thrombosis/Hemostasis 05/2008; 14(2):186-92. · 1.33 Impact Factor
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Hideki Nomura,
Hideo Wada,
Toshiro Mizuno,
Naoyuki Katayama,
Yasunori Abe,
Maki Noda,
Kaname Nakatani, Takeshi Matsumoto,
Satoshi Ota,
Norikazu Yamada,
Akihiro Sudo,
Atsumasa Uchida,
Tsutomu Nobori
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ABSTRACT: The D-dimer levels are considered to be useful for the diagnosis of thrombosis, and they can be clinically used as a negative predictive value (NPV). However, evidence for the efficacy of diagnosing thrombosis based on the D-dimer levels is still not well established. The present study was designed to evaluate the cut-off values of D-dimer levels as a negative predictor for thrombosis. The plasma concentrations of D-dimer were measured in inpatients suspected of having thrombosis, and then the findings were evaluated to assess the correlation with the diagnosis of thrombosis. In healthy volunteers, the median value of VIDAS-D-dimer was 0.12 microg/ml, and the 95% confidence interval was from 0.05 to 0.38 microg/ml. However, the plasma D-dimer levels were significantly higher in patients with thrombosis than in those without thrombosis; there was no significant difference in D-dimer levels among various thromboses such as pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). The NPV for venous thromboembolism was 100% in patients with 0.5 microg/ml VIDAS-D-dimer and 1.2 microg/ml LPIA-D-dimer levels. Elevated D-dimer levels might indicate a high risk of thrombosis, especially DVT/PE, and they are thus considered to be useful as a negative predictor for thrombosis.
International Journal of Hematology 05/2008; 87(3):250-5. · 1.27 Impact Factor
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ABSTRACT: Platelets are produced by megakaryocytes (MKs) through proplatelet formation (PPF), or cytoplasmic extensions, in vitro. Through the use of video-enhanced light microscopy, as well as localization of cytoskeletal proteins by confocal microscopy, the reaction of fully mature MK proplatelets, derived from murine embryonic stem cells, to various agents was studied. Calyculin A (protein phosphatase 1/2A inhibitor) treatment induced proplatelet retraction. In MKs with PPF, the expression of actin, myosin IIA, monophosphorylated myosin light chain (MLC-P1), and diphosphorylated myosin light chain (MLC-P2) was diffusely located. Following calyculin A treatment, actin was diffusely localized in retracted MKs and was expressed particularly in the periphery. MLC-P1 was also localized primarily in the periphery; however, MLC-P2 was expressed mostly in the inner area of proplatelets. Protein phosphatase inhibitors may result in increased hyperphosphorylation of localized MLC, which could alter the balance of actomyosin force in a cell, and therefore induce proplatelets retraction.
Biochemical and Biophysical Research Communications 03/2008; 366(3):763-8. · 2.48 Impact Factor
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Toshihiko Kobayashi,
Hideo Wada,
Norihiro Nishioka,
Masae Yamamoto, Takeshi Matsumoto,
Tomomi Tamaru,
Shinsuke Nomura,
Masahiro Masuya,
Yoshitaka Mori,
Kaname Nakatani,
Masakatsu Nishikawa,
Naoyuki Katayama,
Tsutomu Nobori
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ABSTRACT: The ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type I domain 13) related markers were measured in the plasma of healthy volunteers and thrombotic microangiopathy (TMA) patients including thrombotic thrombocytopenic purpura (TTP) to examine their efficacy in the diagnosis of TTP. The plasma levels of the ADAMTS13 antigen and ADAMTS13-factor XI complex were significantly lower in TMA patients with a significant decreased ADAMTS13 activity (and these patients were considered to have TTP) than in the healthy volunteers. The plasma levels of ADAMTS13 antigens closely correlated with those of ADAMTS13-factor XI complex. Autoantibody for ADAMTS 13 was also positive in almost all TTP patients. In addition, the ratio of von Willebrand factor (VWF)/ADAMTS13 activity was significantly high in TTP suggesting that this ratio might be more useful for the differential diagnosis of TTP than the ADAMTS13 assay alone. These findings suggest that ADAMTS13 related markers are useful for the diagnosis and analysis of TTP.
Thrombosis Research 02/2008; 121(6):849-54. · 2.44 Impact Factor
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ABSTRACT: The ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I domain 13) activity was measured by a fluorescence resonance energy transfer (FRET) assay in the plasma of healthy volunteers and thrombotic thrombocytopenic purpura (TTP) patients to examine its usefulness in the diagnosis of TTP. The plasma levels of the ADAMTS13 activity did not show a normal distribution. Its median value was 107% (range: 55-170%) in healthy volunteers, but was significantly lower in patients with TTP (acquired or familial) and in patients with hematopoietic stem cell transplantation. However, it was not significantly lower in patients with antiphospholipid syndrome (APS). The ADAMTS13 activity by a FRET assay was closely correlated with that by the ADAMTS13 multimer method (r=0.816; p<0.001). In 18 patients with less than 10% of ADAMTS13 activity by FRET assay, less than 10% of that by multimer assay was 16, thus suggesting a good correlation for a low level of ADAMTS13. These findings suggest that the ADAMTS13 FRET assay correlates well with the ADAMTS13 multimer method and it is therefore useful for making a diagnosis of TTP.
Thrombosis Research 02/2007; 119(4):447-52. · 2.44 Impact Factor
