T-gamma delta LGL leukemia with complications.
Explore the source record for details and available documents.
Antigens, CD↗
Biomedical subjects
Kazuo Oshimi
Publications and source records attributed to Kazuo Oshimi.
Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma.
Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its frequent adverse effects are manageable, including gastrointestinal symptoms, peripheral neuropathy, and thrombocytopenia. Severe lung toxicity has not previously been reported. Between June 2004 and September 2005, 13 Japanese patients with multiple myeloma were treated with bortezomib in Toranomon Hospital, Juntendo University School of Medicine, and Jichi Medical School. Four of them developed severe pulmonary complications, and 2 died of respiratory failure without progression of underlying disease. To our knowledge, this is the first report on life-threatening pulmonary adverse effects after bortezomib therapy. Previous clinical studies on bortezomib, mostly in the United States and Europe, have shown low incidences of pulmonary adverse effects. Our study suggests that bortezomib can cause serious lung injury, and that its incidence might vary among different ethnicities. Clinicians need to be alert to the possibility.
Aged↗
Treatment of acute myeloid leukemia patients aged more than 75 years: results of the E-AML-01 trial of the Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG).
The feasibility and effects of combination chemotherapy for very elderly patients with acute myeloid leukemia was examined in 65 patients (including previous myelodysplastic syndrome) aged 76 years or morewith a performance status of 0 - 3. Induction chemotherapy was performed with 30 mg/m2 daunorubicin on days 1 - 3, 150 mg/m2 behenoyl cytosine arabinoside on days 1 - 7, and 70 mg/m2 6-mercaptopurine with 300 mg allopurinol taken orally on days 1 - 7 (BHAC-DM). The complete remission (CR) rate was 38.5%, whereas overall survival at 2 and 5 years was 22.0% and 4.7%, respectively. Two- and 5-year survival of CR patients was 41.8% and 11.2%, respectively. The relapse rate of the 25 CR patients was 64.0% and disease-free survival at 2 and 5 years was 21.0% and 11.2%, respectively. The therapy-related mortality rate at induction was 13.8%. BHAC-DM is feasible and effective for selected very elderly acute myeloid leukemia patients.
Aged↗
Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan: a questionnaire-based report from the "lung injury by bortezomib" joint committee of the Japanese society of hematology and the Japanese society of clinical hematology.
Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies to explore the situation and the details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (P = .033, Fisher exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (P = .024; odds ratio, 0.055) and that a previous SCT might increase the risk (P = .042; odds ratio, 13.140). We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning this matter is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy.
Adrenal Cortex Hormones↗
[Acyclovir combined with plasma exchange for disseminated varicella-zoster virus infection after bone marrow transplantation].
In 2001, a 45-year-old man with severe aplastic anemia received a bone marrow transplantation from his HLA-identical sister, 2.5 years after which he developed severe liver dysfunction together with abdominal pain, disturbance of consciousness and generalized vesicles. Disseminated varicella-zoster virus infection was diagnosed by the detection of VZV DNA. Acyclovir and plasma exchange rapidly controlled his VZV-related symptoms and signs. Disseminated VZV infection is often fatal, but acyclovir and plasma exchange may be useful for such infection by reducing the circulating viral load.
Acyclovir↗
[A clinical study of intraocular malignant lymphoma].
PURPOSE: We investigated whether vitreous cytology and the measurement of intravitreous cytokine were useful for the diagnosis of intraocular malignant lymphoma. SUBJECTS AND METHODS: 8 eyes of 5 patients with suspected intraocular malignant lymphoma during the past 15 months. 3 vitreous samples were collected from 3 patients at the time of pars plana vitrectomy. Polymerase chain reaction(PCR) amplification and flowcytometric analysis(FACS) of the vitreous samples were performed. Interleukin (IL)-10 and IL-6 concentrations were measured. RESULTS: Vitreous cytology showed increased atypical B lymphocytes. The vitreous IL-10/IL-6 ratio was higher than 1 in all cases. Monoclonal rearrangement of the immunoglobulin heavy chain gene and the light chain restriction of immunoglobulin were detected. CONCLUSION: The detection of the monoclonality of infiltrated cells into the vitreous by PCR amplification and FACS, and the measurements of IL-10 and IL-6 concentrations in the vitreous fluid may be useful in the diagnosis of intraocular malignant lymphoma.
Adult↗
[Type 1 hyper-IgM syndrome diagnosed in a 28-year-old patient with recurrent infections since childhood].
We report a male patient who was diagnosed as having hyper-IgM syndrome at the age of 28 years old. The patient had a history of recurrent infectious diseases since childhood such as bronchitis and otitis media, with decreased and increased levels of serum IgG and IgM, respectively. Genomic analysis of the CD40 ligand gene revealed deletion of six nucleotides from 475 to 480 followed by a T to A change at 481. These findings were compatible with the diagnosis of type 1 hyper-IgM syndrome. Bearing in mind the fact that only 20% of such patients survive over the age of 25, this patient is considered to be a rare case who was not actually diagnosed as having this disease until 28 years old.
Adult↗
[Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan: a questionnaire-based report from the "Lung Injury by Bortezomib" Joint Committee of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology].
Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies in order to explore the situation and details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (p = 0.033 by Fischer's exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (p = 0.024; odds ratio = 0.055) and that a previous SCT might increase the risk (p = 0.042; odds ratio = 13.140). We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning these matters is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy. Note that this report has the same contents as the article appeared in the International Journal of Hematology (vol. 84, p406-412, 2006) by permission of both the editorials of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology, and should be considered as the Japanese translation of the article.
Adrenal Cortex Hormones↗
Blastic natural killer cell lymphoma/leukemia (CD56-positive blastic tumor): prognostication and categorization according to anatomic sites of involvement.
BACKGROUND: Blastic natural killer (NK) cell lymphoma/leukemia (BNKL) is an immature CD56-positive neoplasm, which was recognized recently and characterized by systemic proliferation of tumor cells including skin, lymph node, and bone marrow. METHODS: The current study analyzed 47 patients with BNKL (27 had leukemias and 20 had lymphomas). Patient data were collected for the survey of the NK-Cell Tumor Study Group. RESULTS: There were 33 males and 14 females, with a median age of 53 years (range, 3 months to 89 years). There were few clinicopathologic differences between the leukemia and lymphoma types. Cutaneous involvement was noted at diagnosis in 28 patients, who presented a tendency for older age of onset (median: 56 vs. 46 years, P = 0.11) than patients with noncutaneous BNKL. Cutaneous BNKL showed less frequent mediastinal involvement (4% vs. 53%, P = 0.0002) and less severe thrombocytopenia (P =0 .03). Phenotypic characteristics were also different, with cutaneous BNKL favoring CD4 and HLA-DR expression, and noncutaneous BNKL favoring CD16 and CD34 expression. Both groups responded well to chemotherapy for lymphoid malignancies, but disease recurrence was frequent. The prognosis of patients with noncutaneous BNKL was significantly poorer than that of patients with cutaneous BNKL (median survival: 15 vs. 25 months, P = 0.02). Multivariate analysis confirmed that cutaneous involvement was a significant and independent prognostic factor for BNKL, as were age of onset and leukocyte count. CONCLUSIONS: These findings suggested that BNKL is a heterogeneous disease and contains at least two subtypes. Although further investigations are needed to settle a marker for distinction, the presence of cutaneous involvement is a useful prognostic factor.
Adolescent↗
Retroviral expression screening of oncogenes in natural killer cell leukemia.
Aggressive natural killer cell leukemia (ANKL) is an intractable malignancy that is characterized by the outgrowth of NK cells. To identify transforming genes in ANKL, we constructed a retroviral cDNA expression library from an ANKL cell line KHYG-1. Infection of 3T3 cells with recombinant retroviruses yielded 33 transformed foci. Nucleotide sequencing of the DNA inserts recovered from these foci revealed that 31 of them encoded KRAS2 with a glycine-to-alanine mutation at codon 12. Mutation-specific PCR analysis indicated that the KRAS mutation was present only in KHYG-1 cells, not in another ANKL cell line or in clinical specimens (n=8).
3T3 Cells↗
NK-cell neoplasms in Japan.
Neoplasms putatively originating from precursor and mature natural killer (NK) cells are rare, and their clinical features are unclear. A nationwide survey was performed in Japan to clarify the clinical features of these neoplasms diagnosed between 1994 and 1998, and data for 237 patients who met the criteria for putative NK cell-lineage neoplasms were analyzed. Among them, 11 had myeloid/NK-cell precursor acute leukemia, 15 blastic NK-cell lymphoma, 21 precursor NK-cell acute lymphoblastic leukemia, 22 aggressive NK-cell leukemia/lymphoma, 149 nasal-type NK-cell lymphoma (123 nasal and 26 extranasal) and 19 chronic NK lymphocytosis. The median overall survival time of patients with aggressive NK-cell leukemia/lymphoma was 2 months, which for chronic NK lymphocytosis was more than 8 years, and that for the other types of NK-cell neoplasms was between 6 and 22 months. Nasal NK-cell lymphoma and extranasal NK-cell lymphoma share the same histology. The age of affliction was the same, but the sex was different with males predominantly having nasal NK-cell lymphoma and females extranasal NK-cell lymphoma. Patients with extranasal NK-cell lymphoma had the tendency to exhibit a more advanced state of disease, with significantly higher International Prognostic Index and LDH levels, and significantly lower hemoglobin and platelet levels. The overall survival, however, did not differ significantly. Precursor NK-cell acute lymphoblastic leukemia and blastic NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of blastic cells in the bone marrow or peripheral blood, but there were no significant differences for affected age, gender, involved sites or prognosis. Aggressive NK-cell leukemia/lymphoma and extranasal NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of large granular lymphocytes in the bone marrow or peripheral blood and it is possible that aggressive NK-cell leukemia/lymphoma is a leukemic phase of extranasal NK-cell lymphoma. The incidence of skin involvement, however, was significantly higher for extranasal NK-cell lymphoma, suggesting that the two diseases are different. In nasal NK-cell lymphoma, Epstein-Barr virus in tumor cells was detected in all patients tested, suggesting its causative role.
Disease-Free Survival↗
Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasms.
The efficacy of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) for natural killer (NK)-cell neoplasms is unknown. We investigated the results of allo-HSCT for NK-cell neoplasms between 1990 and 2003 through questionnaires. After reclassification by a haematopathologist, of 345 patients who underwent allo-HSCT for malignant lymphoma, 28 had NK-cell neoplasms (World Health Organization classification): extranodal NK/T-cell lymphoma (n=22), blastic NK-cell lymphoma (n=3), and aggressive NK-cell leukaemia (n=3). Twelve were chemosensitive and 16 chemorefractory. Twenty-two had matched-related donors. Stem-cell source was bone marrow in eight and mobilised peripheral blood in 20. Conditioning regimens were myeloablative (n=23) and non-myeloablative (n=5). Grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD developed in 12 and 8 respectively. Eight died of disease progression, three of infection, two of acute GVHD, one of veno-occlusive disease, one of interstitial pneumonitis, and one of thrombotic microangiopathy. Two-year progression-free and overall survivals were 34% and 40% respectively (median follow-up, 34 months). All patients who did not relapse/progress within 10 months achieved progression-free survival (PFS) during the follow-up. In multivariate analysis, stem cell source (BM versus peripheral blood; relative risk 3.03), age (>or=40 years vs. <40 years; relative risk 2.85), and diagnoses (extranodal NK/T-cell lymphoma versus others; relative risk 3.94) significantly affected PFS. Allo-HSCT is a promising treatment for NK-cell neoplasms.
Adult↗
Selective apoptosis of natural killer-cell tumours by l-asparaginase.
We examined the effectiveness of various anti-tumour agents to natural killer (NK)-cell tumour cell lines and samples, which are generally resistant to chemotherapy, using flow cytometric terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) assay. Although NK-YS and NK-92 were highly resistant to various anti-tumour agents, l-asparaginase induced apoptosis in these two NK-cell lines. NK-cell leukaemia/lymphoma and acute lymphoblastic leukaemia (ALL) samples were selectively sensitive to l-asparaginase and to doxorubicin (DXR) respectively. Samples of chronic NK lymphocytosis, an NK-cell disorder with an indolent clinical course, were resistant to both drugs. Our study clearly separated two major categories of NK-cell disorders and ALL according to the sensitivity to DXR and l-asparaginase. We examined asparagine synthetase levels by real-time quantitative polymerase chain reaction (RQ-PCR) and immunostaining in these samples. At least in nasal-type NK-cell lymphoma, there was a good correlation among asparagine synthetase expression, in vitro sensitivity and clinical response to l-asparaginase. In aggressive NK-cell leukaemia, although asparagine synthetase expression was high at both mRNA and protein levels, l-asparaginase induced considerable apoptosis. Furthermore, samples of each disease entity occupied a distinct area in two-dimensional plotting with asparagine synthetase mRNA level (RQ-PCR) and in vitrol-asparaginase sensitivity (TUNEL assay). We confirmed rather specific anti-tumour activity of l-asparaginase against NK-cell tumours in vitro, which provides an experimental background to the clinical use of l-asparaginase for NK-cell tumours.
Antineoplastic Agents↗
Improvement of idiopathic thrombocytopenic purpura by antithyroid therapy.
Here we report a case of idiopathic thrombocytopenic purpura accompanied by Graves' disease. Improvement in thyroid function with methimazole led to the spontaneous recovery of the platelet count from 8 x 10(9)/L to 84 x 10(9)/L. Furthermore, the second fall and recovery of the platelet count well coincided with the recurrence of hyperthyroidism after the discontinuation of methimazole and its normalization by resumption of the drug, respectively. These parallel fluctuations of platelet and thyrotropin because of the cessation and resumption of antithyroid therapy suggests that correction of hyperthyroidism may be beneficial to the control of an imbalance in the immune system which impairs not only thyroid but also the platelet.
Adult↗
Methylation status analysis of cell cycle regulatory genes (p16INK4A, p15INK4B, p21Waf1/Cip1, p27Kip1 and p73) in natural killer cell disorders.
Natural killer (NK) cell disorders are rare diseases. Genetic abnormalities of the several tumor suppressor genes, including p15INK4B, p16INK4A/p14ARF, p53, p73, and Rb genes have been reported. Deletions and point mutations of these genes are frequently detected in these diseases. It has been reported that tumor suppressor genes are inactivated by DNA methylation of the promoter region and/or first exon of the genes in a variety of human cancers. In this study we analyze the methylation status of the genes associated with cell cycle regulation, including p16INK4A, p15INK4B, p21/Waf1/Cip1, p27/Kip1, p73, and p14ARF, by methylation specific (MS) PCR and/or bisulfite sequencing. We examined 29 cases of NK cell disorders (five aggressive NK cell leukemia/lymphoma, three blastic NK cell lymphoma/leukemia, five nasal NK cell lymphoma, three myeloid/NK cell precursor acute leukemia, 13 chronic NK lymphocytosis). We found methylation of the first exon of the p16INK4A gene in two cases (one aggressive, one blastic), and methylation of the p14ARF gene in one aggressive NK cell leukemia. Bisulfite sequencing revealed that methylation of the p15 and p27 genes was rare in these disorders. MS-PCR suggested that the p73 and p21 genes were methylated in seven cases, respectively (p73: one blastic, one nasal, five chronic; p21: one myeloid/NK, one aggressive, one nasal, and four chronic); bisulfite sequencing confirmed that methylated alleles of these genes were dominant in the samples except three cases (one myeloid/NK, one aggressive, and one chronic) in which methylated alleles of the p21 genes were less than 34% of all alleles. These results suggested that inactivation of the cell cycle regulatory genes by DNA methylation could be associated with tumorigenesis in NK cell disorders, not only aggressive subtypes but also chronic subtype.
Base Sequence↗
Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection.
After the first attachment of virus to the cell surface through a primary receptor, efficient entry of virus requires the presence of a coreceptor. For adeno-associated virus type 2 (AAV2) infection, heparan sulfate proteoglycan is supposed as the primary receptor, and alphavbeta5 integrin and FGFR1 are reported to act as coreceptors. In this study, we were able to demonstrate that hepatocyte growth factor receptor, c-Met, is also a coreceptor for AAV2 infection. AAV2-mediated transgene analyses revealed that c-Met expression significantly up-regulated transgene expression without increasing AAV2 cell binding. Moreover, a viral overlay assay elucidated the physical interaction between AAV2 and the beta subunit of c-Met. These data suggest that c-Met plays the role of coreceptor for AAV2 infection by facilitating AAV2 internalization into the cytoplasm.
3T3 Cells↗
[DNA diagnosis in hematologic malignancies].
Genetic microarrays applied to hematologic malignancies identified a number of subgroups with a defined gene expression pattern, which were not identified by morphology, cytogenetics or molecular genetics. In many cases, these expression patterns links tumor cells to the normal developmental counterpart, and represent distinct disease subgroups with different clinical presentations and outcomes. Furthermore, genetic microarrays will be useful in predicting prognosis and identifying novel target of therapy.
Hematologic Neoplasms↗
Mxi1 isoforms are expressed in hematological cell lines and normal bone marrow.
Mxi1 protein is a basic helix-loop-helix, leucine zipper (bHLHZIP) transcriptional factor, which dimerizes with the Max protein. This heterodimer binds a specific DNA sequence (E-box) and suppresses transcription of target genes. On the other hand, c-Myc protein is also a bHLHZIP protein that dimerizes with Max, binds the identical E-box sequence but activates transcription of the target genes. We report that hematopoietic cells have three novel Mxi1 transcripts: Mxi-D lacks exon 3, which encodes the basic region; Mxi-ND lacks the N-terminal mSin3 binding region and the DNA binding region; and Mxi-NF lacks the N-terminal mSin3 binding region. In normal bone marrow and hematological cell lines, the dominantly expressed isoforms are Mxi-D and full-length Mxi1 (Mxi-F). In GST-pull down assays, the Mxi-D protein binds the Max protein and the PHA2 regions of mSin3 proteins. Whereas the Mxi-F/Max heterodimer binds the E-box sequence, Mxi-D/Max heterodimer can not bind this sequence in electrophoretic mobility shift assays. In reporter gene assay, Mxi-D suppresses transcription as strongly as Mxi-F. In colony formation assay using Rat1 fibroblast cells, Mxi-D cannot suppress clonal growth stimulated by c-Myc as strongly as Mxi-F. In summary, Mxi-D may play an important role in the c-Myc family protein network acting as a dominant negative isoform of Mxi-F since: i) Mxi-D can dimerize with Max in vitro; ii) Mxi-D/Max heterodimers cannot bind E-box in vitro, iii) Mxi-D cannot suppress clonal growth stimulated by c-Myc.
Basic Helix-Loop-Helix Proteins↗