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T Doi,
H Takiuchi,
A Ohtsu,
N Fuse,
M Goto,
M Yoshida,
N Dote,
Y Kuze,
F Jinno,
M Fujimoto, T Takubo,
N Nakayama,
R Tsutsumi
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ABSTRACT: This phase I first-in-human study was conducted in Japanese patients to investigate the safety, pharmacokinetics (PKs), and determine the maximum tolerated dose (MTD) of oral TAK-285, a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2.
The TAK-285 dose was escalated until MTD was determined. A second patient cohort received TAK-285 at the MTD for at least 4 weeks. RESULTs: In all, 26 patients received TAK-285 at doses ranging from 50 to 400 mg once daily (q.d.) or twice daily (b.i.d.); 20 patients made up the dose escalation cohort and the remaining 6 patients were the repeated administration cohort. TAK-285 was well tolerated. Dose-limiting toxicities noted in two patients who received 400 mg b.i.d. were grade 3 increases in aminotransferases and grade 3 decreased appetite. Consequently, the MTD was determined to be 300 mg b.i.d. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300 mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300 mg b.i.d.
The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.
British Journal of Cancer 02/2012; 106(4):666-72. · 5.04 Impact Factor
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ABSTRACT: A 33-year-old male with refractory relapsed central nervous system lymphoma underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-identical sibling after reduced-intensity conditioning chemotherapy. The preparative regimen for allo-HSCT consisted of fludarabine and busulfan. Cyclosporine (CsA) and short-term methotrexate were used as prophylaxis for acute graft-versus-host disease (GVHD). Although CsA was quickly reduced to induce a graft-versus-lymphoma (GVL) effect, no symptoms of GVHD and GVL effect were evident. Donor lymphocyte infusion (DLI) was performed on day +40 following transplantation. The patient developed acute GVHD (grade III) after DLI, and lymphoma regression was observed after the occurrence of GVHD. Four months after transplantation, complete remission was achieved with extensive chronic GVHD, and the patient continues to be disease free at 15 months after transplantation.
Annals of Hematology 07/2003; 82(6):371-3. · 2.62 Impact Factor
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ABSTRACT: The association between Helicobacter pylori ( H. pylori) infection and idiopathic thrombocytopenic purpura (ITP) has been reported by several groups. We investigated the prevalence of H. pylori infection and the effectiveness of its eradication in Japanese patients with ITP. H. pylori infection was found in 21 of 30 patients (70.0%) by (13)C urea breath test and presence of serum antibodies to H. pylori. H. pylori was eradicated in 18 of the 21 infected patients (85.7%) by administration of a proton pump inhibitor and two kinds of antibiotics. In only one patient was medication discontinued due to skin rash on the 4th day of treatment. Platelet recovery was obtained in ten patients (55.6%). In two patients with treatment failure, platelet recovery was obtained after successful re-eradication. In three patients without H. pylori infection, platelet counts did not significantly increase with the same treatment. On the other hand, eradication therapy did not affect platelet counts in patients with gastric ulcer. In conclusion, H. pylori eradication can be used for initial treatment with tolerable adverse effects in some ITP patients.
Annals of Hematology 02/2003; 82(1):30-2. · 2.62 Impact Factor
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ABSTRACT: Myosin is a functional protein associated with cellular movement, cell division, muscle contraction and other functions. Members of the myosin super-family are distinguished from the myosin heavy chains that play crucial roles in cellular processes. Although there are many studies of myosin heavy chains in this family, there are fewer on non-muscle myosin heavy chains than of muscle myosin heavy chains. Myosin is classified as type I (myosin I) or type II (myosin II). Myosin I, called unconventional myosin or mini-myosin, has one head, while myosin II, called conventional myosin, has two heads. We transfected myosin heavy polypeptide 9 (MYH9) into HeLa cells as a fusion protein with enhanced green fluorescent protein (EGFP) and analyzed the localization and distribution of MYH9 in parallel with those of actin and tubulin. The results indicate that MYH9 colocalizes with actin stress fibers. Since it has recently been shown by genetic analysis that autosomal dominant giant platelet syndromes are MYH9-related disorders, our development of transfected EGFP-MYH9 might be useful for predicting the associations between the function of actin polymerization, the MYH9 motor domain, and these disorders.
European journal of histochemistry: EJH 02/2003; 47(4):345-52. · 1.69 Impact Factor
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ABSTRACT: The feasibility of CTAD (a mixture of citrate, theophylline, adenosine and dipyridamole) as a new anticoagulant for medical laboratory use was studied prospectively. Whole blood anticoagulated with CTAD exhibited results very similar to those of blood anticoagulated with EDTA on complete blood count and automated white cell differential except for a slight decrease in platelet count and mean platelet volume. Chemistry test data for plasma obtained from CTAD whole blood were close to those obtained for matched sera. Among coagulation tests, prothrombin time, activated partial thromboplastin time and fibrinogen concentrations were close to those obtained with citrate plasma. Based on the results, CTAD was judged to be a good candidate as a new anticoagulant.
Journal of Automated Methods and Management in Chemistry 02/2003; 25(1):17-20. · 0.47 Impact Factor
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S Nishiki,
M Hino,
T Kumura,
S Hashimoto,
K Ohta,
T Yamane, T Takubo,
N Tatsumi,
S Kitagawa,
T Kamitani,
Y Watanabe,
E Shimada,
T Juji,
S Iida
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ABSTRACT: A 71-year-old Japanese male with myelodysplastic syndrome progressing to overt leukaemia and hepatocellular carcinoma developed dyspnea and urticaria immediately after infusion of platelet concentrate (PC). He exhibited an identical reaction following blood transfusion. Serum haptoglobin was undetectable. The patient was determined to be homozygous for Hp(del) by polymerase chain reaction (PCR). Antibody to haptoglobin was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. No antibodies against human leucocyte antigen (HLA) or platelet-specific antigens were detected. Washed PC and washed red blood cells were effective in preventing the transfusion-related anaphylactoid reactions.
Transfusion Medicine 03/2002; 12(1):71-3. · 1.14 Impact Factor
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T Takubo,
H Shibata,
Y Terada,
Y Aoyama,
H Nakamae,
R Yamamura,
E Shima,
K Makita,
K Tanaka,
K Ohta,
T Yamane,
M Hino,
S Hashimoto,
T Kamitani,
N Tatsumi
Haematologia 02/2002; 32(2):147-9.
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T Takubo,
H Kanashima,
Y Terada,
H Shibata,
Y Aoyama,
H Nakamae,
R Yamamura,
E Shima,
K Makita,
K Tanaka,
K Ohta,
T Yamane,
M Hino,
T Kamitani,
N Tatsumi
Haematologia 02/2002; 32(1):97-100.
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T Takubo,
H Kanashima,
Y Terada,
H Shibata,
Y Aoyama,
H Nakamae,
R Yamamura,
E Shima,
K Makita,
K Tanaka,
K Ohta,
T Yamane,
M Hino,
T Kamitani,
N Tatsumi,
K Ohshima
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ABSTRACT: The E-cadherins are a family of cell-cell adhesion molecules. These molecules exhibit Ca2+ dependent cell adhesion and are expressed on epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. We determined serum E-cadherin levels in 30 patients with non-Hodgkin's lymphoma (NHL) using an enzyme immunoassay and then investigated whether E-cadherin is expressed on lymphoma cells in lymph nodes of three cases selected to analyze from 15 cases of serum E-cadherin levels over mean + 2SD with monoclonal antibody immunohistochemistry. Results indicated that E-cadherin antigen is expressed on the lymphoma cells in these three patients with NHL, and that soluble E-cadherin might be released into blood from lymphoma cells. Expression of E-cadherin may contribute to the morphological appearance of some malignant lymphoma, although no conclusion can be drawn based on such small number of patients analyzed.
Haematologia 02/2002; 32(1):67-72.
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T Takubo,
H Kanashima,
Y Terada,
Y Aoyama,
H Nakamae,
R Yamamura,
E Shima,
K Makita,
K Tanaka,
K Ohta,
T Yamane,
M Hino,
T Kamitani,
N Tatsumi
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ABSTRACT: E-cadherin is a transmembrane glycoprotein that mediates Ca2+-dependent intracellular adhesion in normal epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. However, the role of E-cadherin in haematopoietic cells is less clear. In this study, serum E-cadherin levels were therefore determined in patients with acute or chronic leukaemia, malignant lymphoma or myelodysplastic syndromes. Significant elevation of serum E-cadherin levels was detected in patients with haematological malignancies, and between types of acute leukaemias or subtypes of myelodysplastic syndromes, stages of malignant lymphoma, and phases of chronic leukaemia, respectively, compared with those in healthy adult volunteers. These findings suggest that E-cadherin might be expressed in malignant haematopoietic cells and might be useful as a diagnostic indicator in haematological malignancies.
Haematologia 02/2002; 31(4):319-25.
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E Shima,
M Hino,
T Yamane,
Y Aoyama,
H Nakamae,
R Yamamura,
K Makita,
Y Sugano,
S Yasuda, T Takubo,
K Ohta,
N Tatsumi
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ABSTRACT: Rhabdomyolysis is an unusual complication of hematopoietic stem cell transplantation (HSCT). Cyclophosphamide has been one of the key drugs in the most common preparative regimen for HSCT. We present here a rare case of acute rhabdomyolysis following administration of high-dose cyclophosphamide. A 47-year-old woman with adult T-cell leukemia in remission was treated with high-dose cyclophosphamide as a preparative regimen for allogeneic bone marrow transplantation. Nineteen hours later, general convulsions and acidosis suddenly occurred. Levels of serum creatine kinase (skeletal muscle type), myoglobin, and aldolase were markedly elevated to 32870 IU/l, 640 ng/ml, and 240.3 IU/l, respectively. Rhabdomyolysis caused by high-dose cyclophosphamide was diagnosed, and the preparative chemotherapy was discontinued. Subsequently, her muscular signs and symptoms improved, and the results of laboratory examinations returned to normal after 2 weeks. She had previously been treated with conventional doses of cyclophosphamide, doxorubicin, vincristine, and prednisolone without evidence of rhabdomyolysis. Acute rhabdomyolysis may be an adverse effect specific to high-dose cyclophosphamide therapy.
Annals of Hematology 02/2002; 81(1):55-6. · 2.62 Impact Factor
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Y Aoyama,
T Yamane,
M Hino,
K Ohta,
H Nakamae,
R Yamamura,
K R Koh, T Takubo,
T Inoue,
Y Tatsumi,
N Tatsumi
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ABSTRACT: A 79-year-old Japanese man was admitted to our hospital with dyspnea in June 1999. Physical examination revealed general exanthema, hepatosplenomegaly, and lymphadenopathy. Increased numbers of abnormal cells were observed in peripheral blood; these cells were of lymphoblastic morphology with high nuclear/cytoplasm ratios and few azurophilic granules. Immunophenotypic analysis revealed positivity for CD2, CD4, CD56, and HLA-DR, and negativity for CD3, CD13, CD16, CD33, CD34, and T cell receptor (TCR). On genotypic analysis, TCRgamma chain was rearranged, but neither the TCRbeta chain nor TCRdelta chain. Despite an initial good response to chemotherapy the disease relapsed in the early stage, and the patient died 6 months after diagnosis.
Annals of Hematology 01/2002; 80(12):752-4. · 2.62 Impact Factor
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ABSTRACT: We report 2 cases of bronchus-associated lymphoid tissue lymphoma (BALT lymphoma), which is a rare disease. Patient 1 was a 76-year-old woman with a chief complaint of cough. Since plain chest radiography revealed an abnormal shadow in the hilum of the lung, she visited our hospital. Patient 2 was a 56-year-old man, who had been diagnosed as having pseudolymphoma at a medical check-up in a local hospital. During follow-up, however, he was referred to our hospital because of enlarged tumors and chest pain. In both patients, bronchofiberscopy demonstrated submucosal tumors and biopsy samples showed formation of lymphoepithelial lesions by centrocyte-like cells with a B-cell staining pattern. The patients were therefore diagnosed as having BALT lymphoma. Both received CEOP-E treatment, which improved the clinical symptoms but did not result in complete remission. The patients have been followed up after discontinuation of the medication. The progress of the disease has been slow, and both patients are alive as of September 2001.
[Rinshō ketsueki] The Japanese journal of clinical hematology 01/2002; 42(12):1170-5.
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ABSTRACT: In the modern medical laboratory system, simple and rapid processing of specimens are required. In the current system with the transportation line, its centrifugation part would disturb smooth flow of the testing because it needs much time for the centrifugation. To solve the problems, a serum separation method was tried for the whole blood specimen using poly-L-lysine, concanavalin A and phyto-hemoagglutinin. Ploy-L-lysine with molecular weight 130,000 to 210,000 in a final concentration of 0.1% could accelerate blood sedimentation, although its supernatant contaminated platelets. Concanavalin and phytohemoagulutinin could accelerate the sedimentation and obtained plasma, but the method could yield enough amount of supernatant by 1 hour standing. As the purpose of this study is to develop a centrifugeless method, a sieve method using a steel mesh and a magnet was applied to the mixture of EDTA blood, red-cell adhesives and thrombin. The method was unique to separate plasma, but the yield was not so high and chemistry data were not fitted with serum data in some of tests. Thus, the trial would be a new technology, but it was judged that some further improvement will be needed technically.
Osaka city medical journal 01/2002; 47(2):177-88.
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H. Fujino,
K. Ohta,
A. Taniue,
N. Nagao,
M. Hino,
T. Yamane,
K.-R. Koh,
Y. Takeoka,
A. Hirose,
Y. Aoyama,
H. Nakamae,
Y. Terada, T. Takubo,
N. Tatsumi
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ABSTRACT: Background and Objectives
Anti-Naka, a platelet-specific antibody, occasionally causes platelet-transfusion refractoriness (PTR) together with human leucocyte antigen (HLA) antibodies. Anti-Naka usually appears after frequent platelet transfusions or pregnancy. We report the first case of PTR caused by anti-Naka alone.Materials and MethodsA 19-year-old male patient with testicular tumour showed PTR when receiving his first transfusion of platelets. Screening for platelet antigens and platelet antibodies revealed that he had type I CD36 (Naka) deficiency and that anti-Naka, but not anti-HLA, was present before he received his first transfusion.ResultsThe transfusion of Naka-negative, but HLA non-selected, platelets was effective in raising the platelet count.Conclusion
Clinically significant Naka antibody was present as naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non-transfused male patient.
Vox Sanguinis 12/2001; 81(1):42 - 44. · 2.86 Impact Factor
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ABSTRACT: Tissue factor pathway inhibitor (TFPI) is a protease inhibitor of extrinsic coagulation. The present study investigates the possibility of utilizing TFPI as a universal anticoagulant in clinical laboratory tests. The optimal concentration of TFPI for use in clinical laboratory tests was found to be 1 microl TFPI/ml blood (100 mmol TFPI/ml blood); the subsequent analyses were conducted at this concentration. In hematological tests, complete blood cell count and differential white blood cell count were done with an automatic blood analyzer. The results except for platelet and white blood cell counts were similar for ethylenediaminetetraacetic acid (EDTA)-treated and TFPI-treated samples. The effects of TFPI on platelet count were more pronounced when blood samples were stored at 4 degrees C than at room temperature. The effects of TFPI on cell morphology were evaluated by spreading blood samples into thin films and applying a Giemsa stain. The results showed that TFPI did not alter the morphology of blood cells. An automatic biochemical analyzer performed seventeen basic biochemical tests on serum samples and TFPI-treated plasma samples. The results of seventeen tests were comparable between TFPI-treated samples and EDTA-treated samples. The prothrombin time for TFPI-treated plasma samples was longer than that for citrated plasma samples. Nonetheless, in activated partial thromboplastin time tests, the addition of the reagent caused turbidity and partial coagulation, thus demonstrating that TFPI is not suitable for this assay. These findings suggest that although some tests cannot be performed with TFPI, this compound may be useful as a universal anticoagulant in the future.
The Tohoku Journal of Experimental Medicine 08/2001; 194(3):165-74. · 1.24 Impact Factor
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ABSTRACT: Hematopoietic stem cell transplantation(HSCT) increase the chances of cure of many hematological malignancy. The clinical laboratory plays a major role in support of HSCT. Both transplantation-specific laboratory test(tissue typing, assessment of graft viability/rejection, evaluation of minimal residual disease, and measurement of immunosuppressive drugs) and routine clinical laboratory tests(biochemical, hematological, serological, urinary, bacteriological, and physiological examinations) are significant. Hematopoietic stem cells(HSC) are usually assessed as CD34+ cells, while immature cells determined by automated hematology analyzers can simply evaluate HCS. These automated immature cell counts are earlier markers of engraftment following transplantation than the traditional indicators(neutrophils and platelets). After transplantation, infections, regimen-related toxicities, graft-versus host disease, veno-occlusive disease, and thrombotic microangiopathy are the serious complications, which are causes of expected mortality and morbidity in HSCT. Clinical laboratory monitoring may contribute early diagnosis and treatment of the complications, resulting in prevention of the adverse events.
Rinsho byori. The Japanese journal of clinical pathology 08/2001; 49(7):657-61.
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H Fujino,
K Ohta,
J Taniue,
N Nagao,
M Hino,
T Yamane,
K R Koh,
Y Takeoka,
A Hirose,
Y Aoyama,
H Nakamae,
Y Terada, T Takubo,
N Tatsumi,
A Taniue
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ABSTRACT: Anti-Nak(a), a platelet-specific antibody, occasionally causes platelet-transfusion refractoriness (PTR) together with human leucocyte antigen (HLA) antibodies. Anti-Nak(a) usually appears after frequent platelet transfusions or pregnancy. We report the first case of PTR caused by anti-Nak(a) alone.
A 19-year-old male patient with testicular tumour showed PTR when receiving his first transfusion of platelets. Screening for platelet antigens and platelet antibodies revealed that he had type I CD36 (Nak(a)) deficiency and that anti-Nak(a), but not anti-HLA, was present before he received his first transfusion.
The transfusion of Nak(a)-negative, but HLA non-selected, platelets was effective in raising the platelet count.
Clinically significant Nak(a) antibody was present as naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non-transfused male patient.
Vox Sanguinis 08/2001; 81(1):42-4. · 2.86 Impact Factor
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Y Takeoka,
M Hino,
N Oiso,
S Nishi,
K R Koh,
T Yamane,
K Ohta,
H Nakamae,
Y Aoyama,
A Hirose,
H Fujino, T Takubo,
T Inoue,
N Tatsumi
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ABSTRACT: A 26-year-old woman with idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital because of fever and rash. Blood tests revealed thrombocytopenia, liver dysfunction, coagulopathy, and hyperferritinemia. Bone marrow examination revealed many atypical lymphocytes and some histiocytes with hemophagocytosis. On admission she was diagnosed with rubella virus-associated hemophagocytic syndrome (VHAS), but on laboratory examination, she was seropositive for varicella-zoster virus (VZV)-IgM as well as rubella virus-IgM. She was therefore diagnosed with dual infection by rubella virus and VZV. Her simultaneous rubella virus and VZV infection may have been related to the VAHS pathogenesis. She was treated with prednisolone and gamma globulin therapy and recovered completely.
Annals of Hematology 07/2001; 80(6):361-4. · 2.62 Impact Factor
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ABSTRACT: The reticulocyte count has been conventionally determined using a visual method. Recently, due to technological advances an automated method has come into general use in laboratories. The precision in terms of reproducibility of automated reticulocyte counters has also made rapid progress compared with the visual method. The measurements of reticulocyte counts showed good correlation among the five automated reticulocyte counters and the visual method although the accuracy of an automated method is problematical since it is not sufficient to find the true value. It remains difficult to standardize reticulocyte counting because automated reticulocyte counting is performed in accordance with the procedure specified by the respective manufactures; thus, an external quality control survey was performed for an accuracy assurance of reticulocyte counts with the participation of many laboratories. In the future, it is necessary to develop biological reference materials equal to the true value or to establish other standardization using new technology.
Rinsho byori. The Japanese journal of clinical pathology 06/2001; 49(5):475-9.
