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Atsushi Wakita

Publications and source records attributed to Atsushi Wakita.

15 recordsLinked to original sources
PubMed2004

Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin.

One Japanese pedigree of familial essential thrombocythemia (FET) inherited in an autosomal-dominant manner is presented. A unique point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin 3 (IL-3)-independent survival capacity, whereas those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET deriving from a dominant-positive activating mutation of the c-MPL gene.

Cells, Cultured↗
PubMed2004

Twenty years' experience in allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in the Nagoya Blood and Marrow Transplantation Group.

Between October 1981 and December 2000, 46 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the Nagoya Blood and Marrow Transplantation Group. The median age was 28.5 years (range, 4-51 years). All but one patient achieved engraftment. Grade II-to-IV acute graft-versus-host disease (GVHD) developed in 32.5% of patients, and chronic GVHD developed in 40.5%. The incidences of relapse and treatment-related mortality (TRM) at 5 years were 65% and 26%, respectively. The estimated overall survival rate at 5 years was 23%. Univariate analysis showed that improved disease-free survival (DFS) was independently associated with complete remission (CR) at transplantation (39%), compared with non-CR (8%) (P = .023). Non-CR at transplantation was associated with a higher risk of relapse. Donor type, acute GVHD, and time from diagnosis to HSCT all had a significant effect on TRM. In a multivariate analysis, 9 months or more from diagnosis to HSCT was the only variable statistically significant for DFS (relative risk, 3.22; P = .01). This study demonstrates that allogeneic HSCT cures a significant population of patients with Ph+ ALL. Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS.

Adolescent↗
PubMed2003

Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome.

Adult T-cell leukemia/lymphoma (ATLL) is a distinct clinical entity among mature T-cell neoplasms, and its causative agent has been confirmed to be long-term infection by human T-lymphotropic virus type 1. A recent study demonstrated frequent expression of a chemokine receptor, CC chemokine receptor (CCR)4, which is known as a Th2 marker but not CXC chemokine receptor (CXCR)3, which is known as a Th1 marker, among both ATLL- and human T-lymphotropic virus type 1-immortalized T cells. In this study, immunostaining analysis for CCR4 and CXCR3 expression in ATLL cells obtained from 103 patients with ATLL was performed, and the clinical parameters and overall survival of the CCR4-positive and -negative cases were compared. Ninety-one (88.3%) of the 103 cases were positive for CCR4 staining, whereas only 5 (4.9%) were positive for CXCR3 staining. Positivity for CCR4 was significantly associated with skin involvement (P < 0.05), although there were no significant differences in clinical characteristics between the CCR4-positive and -negative cases at the time of initial diagnosis. CCR4(+) ATLL cells may accumulate in the skin because of the expression of a CCR4 ligand, thymus and activation-regulated chemokine (TARC), on normal and inflamed cutaneous endothelia. As for survival analysis, positivity for CCR4 expression was extracted as an unfavorable prognostic factor as well as other factors, including the presence of B symptoms and extranodal involvement of more than one site. Multivariate analysis confirmed that CCR4 expression was an independent and significant prognostic factor (P < 0.05). Thus, our finding may provide a novel insight into not only the biological but also the clinical features of ATLL.

Adult↗
PubMed2003

T-cell acute lymphoblastic leukemia as a secondary leukemia after a 3-year remission of acute myelocytic leukemia.

Therapy-related myelodysplastic syndrome and therapy-related acute myelocytic leukemia (AML) are now recognized as hematologic malignancies that occur a few years after chemotherapy for primary malignancy with alkylating agents or topoisomerase II inhibitors. The secondary leukemia is usually AML and sometimes is preceded by a myelodysplastic syndrome. Acute lymphoblastic leukemia (ALL) as a secondary leukemia is quite rare, and secondary T-cell ALL after AML is even rarer. We report a case of a 56-year-old woman who developed T-cell ALL after a 3-year remission of AML (M2). We thought that this case would be extremely valuable for studying the etiology and biological characteristics of T-cell ALL as a secondary leukemia after AML.

Chromosomes, Human, Pair 14↗
PubMed2002

Interleukin-13 induces thymus and activation-regulated chemokine (CCL17) in human peripheral blood mononuclear cells.

BACKGROUND: In allergic inflammation involving allergic rhinitis, the predominance of Th(2) lymphocytes is one of the primary causal agents in promotion of the allergic condition. Thymus and activation-regulated chemokine (TARC/CCL17) is a recently identified chemokine that induces the development of Th(2) lymphocytes. One of the sources of TARC has been reported to be peripheral blood mononuclear cells (PBMCs). OBJECTIVE: We investigated TARC production from PBMCs by the stimulation of specific antigens and Th(2) type cytokines. METHOD: PBMCs were isolated from both allergic rhinitis patients and healthy volunteers. PBMCs were incubated with cytokine. TARC mRNA expression was examined by real time PCR methods and the amount of TARC production was examined by ELISA. RESULTS: IL-13 was found to be the most potent inducer for TARC mRNA expression and protein production in PBMCs. Furthermore, tumour necrosis factor alpha and IL-13 synergistically induce TARC. The amount of TARC from allergic rhinitis patients was significantly larger than that from healthy volunteers. Moreover, TARC was induced by a specific antigen, and was 35% inhibited by an anti-IL-13 neutralizing antibody. CONCLUSION: These results indicate that IL-13 is important in TARC mediated Th(2) lymphocytes infiltration in the nasal mucosa.

Adolescent↗
PubMed2002

Superior mesenteric venous thrombosis associated with a familial missense mutation (Pro626Leu) in the SHBG-like domain of the protein S molecule.

A 76-year-old Japanese woman was hospitalized for ileus symptoms caused by extensive thrombosis of the superior mesenteric vein. Because laboratory test results suggested type III protein S (PS) deficiency, molecular changes in PS were investigated. A single-base transition, CCG to CTG at codon 626 in exon XV, resulting in the missense mutation Pro626Leu, was identified in an allele of the patient and in her son. Reverse transcriptase polymerase chain reaction analysis indicated the presence of both normal and mutant types of PS messages in platelet-derived messenger RNAs. Our findings thus suggest that Pro626 in SHBG-like domain 7 may be crucial for in vivo antithrombotic activity of the PS molecule.

Aged↗
PubMed2002

Successful treatment of nasal T-cell lymphoma with a combination of local irradiation and high-dose chemotherapy.

Nasal natural killer (NK)/T-cell lymphoma is characterized by an aggressive clinical course and poor prognosis. The term "NK/T-cell" lymphoma includes both the NK-cell type and the T-cell type, which are classified by immunophenotyping and according to T-cell receptor (TCR) rearrangement. In addition, CD56+ T-cell lymphoma is defined as NK-like T-cell lymphoma. This report concerns a 54-year-old woman with nasal T-cell lymphoma. Its phenotype showed pure T-cell type with CD3+, CD56-, and TCR+ accompanied by Epstein-Barr virus infection. Although the lesions were localized in the nasal mucosa and facial skin (stage IE), local irradiation could not achieve complete remission (CR). We then administered 5 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen followed by high-dose chemotherapy with an autologous peripheral blood stem cell transplantation. This therapy resulted in CR. Our results suggest that this lymphoma subtype may be cured by means of intensive treatment soon after diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Lineage conversion from acute lymphoblastic leukemia to acute myeloid leukemia on rearrangement of the IgH gene in a patient with Down syndrome.

A patient with Down syndrome (DS) at the time of diagnosis of acute lymphoblastic leukemia (ALL) had a relapse with acute myeloid leukemia (AML) after 4 years of complete remission. Although the diagnosis was AML, the leukemic blasts at relapse showed an immunoglobulin H rearrangement that turned out to be identical to that of the initial ALL blasts. It is thought that the leukemic precursor cells of this patient had the potential to differentiate into both lymphoid and myeloid lineages. This case is important for investigating target cells for leukemogenesis in DS.

Adult↗
PubMed2002

Lymphoid blastic crisis of chronic myelogenous leukaemia with inv(16)(p13;q22).

We report a case of chronic myelogeneous leukaemia (CML) in B-lineage lymphoid blastic crisis (BC) having chromosome abnormality, inv(16)(p13;q22) in addition to Philadelphia chromosome, in 20/20 marrow metaphase. Inv(16)(p13;q22) was not observed in cells of chronic phase or accelerate phase. Abnormalities of chromosome 16, including inv(16)(p13;q22), del(16)(q22) and t(16;16)(p13;q22), have been reported mostly in acute myelomonocytic leukaemia (AML), (FAB M4-Eo), and some in CML-BC and myelodysplastic syndrome (MDS) cases. Most of the cases showed increase of myelomonocytic components and abnormal eosinophils with dysplastic granules in the bone marrow (BM). However, our case was diagnosed as lymphoid BC without increase of myelomonocytic components, although some abnormal eosinophilia was seen. To date, lymphoid BC of CML having inv(16)(p13;q22) abnormality has not been reported. The case presented here could be a clue to understand the pathophysiology of inv(16)(p13;q22) leukaemia.

Adult↗
PubMed2002

Neurofibromin and NF1 gene analysis in composite pheochromocytoma and tumors associated with von Recklinghausen's disease.

Composite tumor of pheochromocytoma and neuroblastoma, or ganglioneuroma, or ganglioneuroblastoma (composite pheochromocytoma), also known as mixed neuroendocrine and neural tumor, are sometimes combined with neurofibromatosis type 1 (NF1). To better understand the relationship between NF1 and composite pheochromocytoma, an immunohistochemical study using anti-neuro-fibromin that is an NF1 gene product and DNA sequence of NF1 Exon 31 were carried out in five cases of composite pheochromocytoma and in various tumors from five patients with NF1. Neurofibromin was not expressed in Schwann cells and sustentacular cells of composite pheochromocytomas and was very weakly or negatively expressed in neurofibroma of NF1 patients. However, it was strongly expressed in ganglionic cells and pheochromocytoma cells of the composite pheochromocytomas and also in mucosal ganglioneuromas, a gangliocytic paraganglioma, and in pheochromocytomas from the patients with NF1. Although there was no mutation in NF1 Exon 31, it could not be ruled out that there were mutations in other sites of the NF1 gene. Neurofibromin insufficiency may induce abnormal proliferation of Schwann cells in composite pheochromocytomas as well as in neurofibromatosis.

Adrenal Gland Neoplasms↗
PubMed2002

Aplastic anaemia with 13q-: a benign subset of bone marrow failure responsive to immunosuppressive therapy.

In an attempt to determine the pathological significance of a long arm deletion of chromosome 13 (13q-) in bone marrow failure syndrome, we reviewed the clinical records of nine patients who were initially diagnosed with aplastic anaemia due to bone marrow hypoplasia without dysplasia. Six patients responded to immunosuppressive therapy and the other three improved with steroids. None of the patients developed acute leukaemia (follow up: 54-129 months) and the estimated 5-year survival was 78%. These findings indicate that pancytopenia with 13q- represents bone marrow failure of a benign nature, similar to aplastic anaemia without karyotypic abnormalities, rather than preleukaemia.

Adult↗
PubMed2002

Superior efficacy of MMCP regimen compared with VMCP and MMPP regimens in the treatment of multiple myeloma.

OBJECTIVE: A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL]. METHODS: MCNU (33.3 mg/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks. PATIENTS OR MATERIALS: From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled. RESULTS: Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1 %, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens. CONCLUSION: The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[DAD, new intensive chemotherapy for patients with myeloma: a preliminary report].

A new intensive chemotherapy regimen, DAD, composed of doxorubicin, melphalan and dexamethasone, was given to 17 patients with multiple myeloma. The end point of this regimen was to obtain a deep posttreatment nadir in the M-protein levels so as to increase the chance of plateau attainment which would be associated with prolonged survival in each patient. It was noteworthy that all the 17 evaluable patients achieved a partial response. Nine of the 17 (52.9%) attained a plateau. Ten of the 17 patients (58.8%) obtained a deep posttreatment nadir in their M-protein levels (IgG < 2,000 mg/dl, IgA < 1,000 mg/dl, BJP = 0 g/dl/day), and six of them reached a plateau phase, which was not significantly more frequent than those who did not obtain a deep posttreatment nadir in their M-protein levels (three of seven reached plateau phase). The median survival of the 17 patients (37.6 months) was significantly prolonged compared with that of patients treated with our previous chemotherapy regimens, VMCP (22.5 months) and MMPP (23.5 months), and was comparable to that of MMCP (29.5 months).

Antineoplastic Combined Chemotherapy Protocols↗