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Mihoko Yotsumoto,
Shotaro Hagiwara,
Atsushi Ajisawa,
Junko Tanuma,
Tomoko Uehira,
Hirokazu Nagai,
Yuko Fujikawa,
Shunichi Maeda, Kiyoshi Kitano,
Nobuyoshi Arima,
Kenji Uno,
Toshiki Iwai,
Igen Hongo,
Yasunori Ota,
Katsuyuki Fukutake,
Seiji Okada
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ABSTRACT: The incidence of Hodgkin lymphoma (HL) is paradoxically increasing in the combination anti-retroviral therapy (cART) era. However, there has been no nationwide survey of human immunodeficiency virus (HIV)-associated HL (HIV-HL) in Japan. We retrospectively examined the clinical characteristics and outcomes of 19 newly diagnosed HIV-HL patients at 11 HIV/AIDS and hematology regional hospitals in Japan between 1991 and 2010. At the time of HL diagnosis, 79 % of patients were receiving cART. All the patients, but one received HL diagnoses in the cART era. The median CD4+ cell count at HIV-HL diagnosis was 169/μl. Mixed-cellularity classical Hodgkin lymphoma was the most common subtype occurring in 68 % of the patients; 89 % of the patients were positive for Epstein-Barr virus. Of these 19 patients, 84 % were in advanced stages, with bone marrow involvement observed in 47 % of the patients; 58 % had extranodal sites. All the treated patients were given cART concurrent with HL therapy. The complete remission rate of the treated patients was 87 %. The median OS of the entire cohort was 17 months. These results suggest that the characteristics of HIV-HL in Japan are more aggressive than those of non-HIV-associated HL in Japan, but standard chemotherapy is effective and feasible.
International journal of hematology 07/2012; 96(2):247-53. · 1.17 Impact Factor
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ABSTRACT: Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/microL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC.
Journal of Korean medical science 03/2010; 25(3):476-80. · 0.84 Impact Factor
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ABSTRACT: Herein, we encountered an 89-year-old woman with pancreatic cancer who presented with fever without infective focus, leukocytosis of 45,860 /microL, and elevation of serum granulocyte-colony stimulating factor (G-CSF). The patient could not receive any curative therapy due to an extremely aggressive clinical course. Specimens taken at necropsy revealed an adenosquamous carcinoma positive for G-CSF by immunohistochemistry; it was only the second reported case to date. She was finally diagnosed with G-CSF-producing pancreatic cancer. In light of the above, clinicians should consider the presence of G-CSF-producing tumors, including pancreatic cancer, when presented with patients showing leukocytosis of unknown origin and fever without infective focus.
Internal Medicine 02/2009; 48(9):687-91. · 0.94 Impact Factor
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Tadanobu Nagaya,
Naoki Tanaka,
Atsushi Kamijo,
Satoru Joshita,
Koh Nakazawa,
Hideharu Miyabayashi,
Suguru Yoneda,
Tetsuya Ito,
Michiharu Komatsu,
Eiji Tanaka, Kiyoshi Kitano
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ABSTRACT: A 33-year-old Japanese man was referred to our hospital after a huge intrapelvic tumor with bilateral hydronephrosis was found following persistent lumbago. Natural killer/T-cell lymphoma was suspected due to positive immunostaining for CD56, but CHOP therapy was ineffective. Re-evaluation of the tumor cells showed that they were positive for CD99, neuron-specific enolase, and synaptophysin and had a t(11 ; 22) (q24 ; q12) translocation, leading to the revised diagnosis of primitive neuroectodermal tumor (PNET). Systemic chemotherapies and radiation therapy were added to surgical resection, and no recurrence has been detected for 3 years. Taken together, PNET may be considered in adult patients with CD56-positive tumors.
Internal Medicine 02/2009; 48(15):1267-72. · 0.94 Impact Factor
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ABSTRACT: Aggressive natural killer cell leukaemia (ANKL) is a malignant disorder of mature NK cells with a poor prognosis, for which no effective therapeutic approach has been established. We investigated the role of allogeneic haematopoietic cell transplantion (allo-HCT) in ANKL.
Three patients with ANKL received allo-HCT and seven did not. Epstein-Barr virus (EBV) viral load (VL) of the whole blood was measured with real-time quantitative polymerase chain reaction.
We transplanted three patients using a myeloablative conditioning regimen with human leucocyte antigen (HLA) two-loci mismatched cord blood (n = 2), or HLA-matched sibling bone marrow (n = 1). In one patient, a second transplantation from the haploidentical mother was also performed at relapse. No patients were in complete remission (CR) at the time of conditioning. After allo-HCT, all three achieved and maintained CR. One died from sepsis and the other relapsed, received the second transplantation and achieved a second CR. EBV VL was quite high in all three at presentation and its significant reduction was observed after allo-HCT. Although their backgrounds were not different from those without allo-HCT, patients with allo-HCT had a better outcome.
Allo-HCT might be a promising therapy for ANKL with curative potential.
European Journal Of Haematology 06/2008; 81(2):107-11. · 2.61 Impact Factor
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ABSTRACT: Here we report two patients with hematological malignancies associated with complications of fatal cardiac zygomycosis. The first case, a 72-year-old man with myelodysplastic syndrome being treated with low-dose cytarabine, died of sudden cardiac arrest. An autopsy revealed disseminated zygomycosis accompanied with occlusion of the coronary artery by fungal thrombi. The second case, a 52-year-old woman with acute lymphoblastic leukemia, developed febrile neutropenia and skin eruptions with induration on the face and extremities during the first induction chemotherapy. She experienced sudden bradycardia with unstable hemodynamics and died of acute myocardial infarction. Histological examination of a skin biopsy demonstrated zygomycosis. In light of the above, it should be kept in mind that cardiac zygomycosis might occur in hematologically compromised patients presenting with acute myocardial infarction.
Internal Medicine 02/2008; 47(9):839-42. · 0.94 Impact Factor
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Hideki Makishima,
Toshiro Ito,
Kayoko Momose,
Hideyuki Nakazawa,
Shigetaka Shimodaira,
Yuji Kamijo,
Yozo Nakazawa,
Naoaki Ichikawa,
Mayumi Ueno,
Hikaru Kobayashi, Kiyoshi Kitano,
Hiroshi Saito,
Kendo Kiyosawa,
Fumihiro Ishida
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ABSTRACT: NK cell-type lymphoproliferative disease of granular lymphocytes can be subdivided into aggressive NK-cell leukemia (ANKL) and chronic NK-cell lymphocytosis (CNKL). Hepatosplenomegaly is observed in ANKL patients, and hepatic failure is a common cause of death. Significant numbers of ANKL cells were pathologically observed in sinusoidal and interlobular regions of the liver, and in the splenic red pulp. In our previous study, ANKL cells were simultaneously positive for CXCR1 and CCR5. So, in order to elucidate the mechanism in the systemic migration of ANKL cells, we investigated the expression of the corresponding chemokines in ANKL compared with CNKL. The serum level of IL-8, MIP-1alpha and MIP-1beta was significantly elevated in ANKL patients, and ANKL cells were highly positive for IL-8, RANTES, MIP-1alpha and MIP-1beta according to intracellular staining and RT-PCR. These chemokines were also positively stained in hepatocytes. The interaction between Fas and Fas ligand (FasL) is supposed to be one of the mechanisms for liver dysfunction in ANKL. The serum concentration of soluble FasL was significantly high in ANKL patients, and ANKL cells expressed FasL protein in the cytoplasm. These results suggest that the chemokine system plays an important role in the transmigration of FasL-expressing ANKL cells.
Leukemia Research 10/2007; 31(9):1237-45. · 2.92 Impact Factor
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ABSTRACT: Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.
European Journal Of Haematology 09/2006; 77(3):255-8. · 2.61 Impact Factor
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Kiyoshi Kitano,
Yukio Gibo,
Atsushi Kamijo,
Kiyoshi Furuta,
Satohiro Oguchi,
Satoru Joshita,
Yasufumi Takahashi,
Fumihiro Ishida,
Masanori Matsumoto,
Masahito Uemura,
Yoshihiro Fujimura
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ABSTRACT: A deficiency of ADAMTS13 leads to platelet clumping and/or thrombi formation, finally resulting in thrombotic thrombocytopenic purpura (TTP). In this study, a 62-year-old male with chronic hepatitis C developed TTP a month after long-term pegylated-interferon (PEG-IFN) treatment. The observed low level of activity of plasma ADAMTS13 following PEG-IFN treatment was shown to gradually increase with the improvement of TTP, while the titer of an inhibitory anti- ADAMTS13 IgG antibody decreased concomitant with the increase in ADAMTS13 activity. Serial determination of ADAMTS13 activity and its inhibitor may provide useful information for the diagnosis and treatment of IFN-associated TTP, as well as its pathogenesis.
Haematologica 09/2006; 91(8 Suppl):ECR34. · 6.42 Impact Factor
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AIDS 10/2005; 19(14):1547-8. · 6.24 Impact Factor
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Kiyoshi Kitano,
Naoaki Ichikawa,
Bilkis Mahbub,
Mayumi Ueno,
Toshiro Ito,
Sigetaka Shimodaira,
Hiroshi Kodaira,
Fumihiro Ishida,
Hikaru Kobayashi,
Hiroshi Saito,
Yoshio Okubo,
Hideo Enokihara,
Kendo Kiyosawa
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ABSTRACT: We describe a patient with eosinophilia and an abnormal CD3+4−8−αβ+ T-cell population. Chromosomal analysis of sorted CD3+4−8− cells revealed abnormal karyotypes on chromosome 16. In the presence of IL-2 the production of IL-5 from CD3+4−8− cells was higher than that from CD3+4+/8+ cells. Eosinophil survival-enhancing activity in the patient serum was inhibited by a combination of anti-IL-5 and anti-GM-CSF monoclonal antibodies. These data suggest that increased production of IL-5 and GM-CSF from the abnormal CD3+4−8− cells might cause eosinophilia.
British Journal of Haematology 11/2003; 92(2):315 - 317. · 4.94 Impact Factor
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ABSTRACT: A 55-year-old woman presented with massive refractory ascites in the course of idiopathic myelofibrosis. The ascites was exudative, and a cytological examination revealed granulocytes of varying maturity, erythroblasts, and megakaryocytes with trisomy 8. The ascites was assumed to have developed from peritoneal extramedullary hematopoiesis. An abnormal karyotype in the cells in the ascitic fluid, which was the same abnormality as in peripheral blood, helped to prove extramedulary hematopoiesis in this case, which can be an aid in making a differential diagnosis in cases of ascites associated with myelofibrosis.
Internal Medicine 07/2003; 42(6):525-8. · 0.94 Impact Factor
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Nihon Naika Gakkai Zasshi 12/2002; 91(11):3289-91.
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Hideki Makishima,
Fumihiro Ishida,
Toshiro Ito, Kiyoshi Kitano,
Shuichi Ueno,
Ken Ohmine,
Yoshihiro Yamashita,
Jun Ota,
Masao Ota,
Kazuyoshi Yamauchi,
Hiroyuki Mano
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ABSTRACT: Lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the clonal proliferation of large granular lymphocytes of either T- or natural killer cell origin. To better understand the nature of T cell-type LDGL, we purified the CD4-CD8+ proliferative fractions from LDGL patients (n=4) and the surface marker-matched T cells isolated from healthy volunteers (n=4), and compared the expression profiles of 3456 genes using DNA microarray. Through this analysis, we identified a total of six genes whose expression was active in the LDGL T cells, but silent in the normal ones. Interestingly, expression of the gene for interleukin (IL) 1beta was specific to LDGL T cells, which was further confirmed by the examination of the serum level of IL-1beta protein. Given its important role in inflammatory reactions, the disease-specific expression of IL-1beta may have a causative relationship with the LDGL-associated rheumatoid arthritis. Spectratyping analysis of the T-cell receptor repertoire also proved the monoclonal or oligoclonal nature of LDGL cells. These data have shown that microarray analysis with a purified T-cell subset is an efficient approach to investigate the pathological condition of Tcell-type LDGL.
British Journal of Haematology 09/2002; 118(2):462-9. · 4.94 Impact Factor
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ABSTRACT: To examine the role of the fibrinogen gamma chain in the assembly and secretion of this multichain protein, we synthesized a series of fibrinogen variants with truncated gamma chains, terminating between residues gamma379 and the C-terminus, gamma411. The variant fibrinogens were synthesized from altered gamma-chain complementary DNAs in cultured Chinese hamster ovary cells. Immunoassays of the culture media demonstrated that only those variants with gamma chain longer than 386 residues were secreted and that the concentration of fibrinogen decreased with the length of the gamma chain, from 1.4 microg/mL for normal fibrinogen to 0.39 microg/mL for gamma 387 fibrinogen. Immunoassays of cell lysates showed that all variant gamma chains were synthesized, although the levels varied significantly. For variants longer than 386 residues, levels decreased with length but remained near normal. In contrast, expression of the 4 variants with 386 residues or less was about 20-fold reduced. Quantitative reverse transcription-polymerase chain reaction demonstrated that the gamma-chain messenger RNA level was independent from chain length. Western blot analyses showed that lysates expressing variants with 387 residues or more contained species comparable to the known intermediates in fibrinogen assembly, including half-molecules. For shorter variants, these intermediates were not evident. We conclude that residues near the C-terminus of the gamma chain are essential for fibrinogen assembly, and more specifically, that gamma387 is critical. We propose that the loss of residue gamma387 destabilized the structure of gamma chain, preventing assembly of alphagamma and betagamma dimers, essential intermediates in the assembly of normal fibrinogen.
Blood 06/2002; 99(10):3654-60. · 9.90 Impact Factor
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Fumihiro Ishida,
Mayumi Ueno,
Hitoshi Tanaka,
Hideki Makishima,
Kenichi Suzawa,
Shigetoshi Hosaka,
Eiko Hidaka,
Masayo Ishikawa,
Kazuyoshi Yamauchi, Kiyoshi Kitano,
Kendo Kiyosawa
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ABSTRACT: We report a male patient with acute myelogenous leukemia (AML; French-American-British M2) associated with AML1-ETO. Cytogenetic studies showed a complex karyotype including a novel translocation (8;21;14)(q22;q22;q24) in all analyzed cells. This three-way translocation was confirmed with spectral karyotyping. Reverse transcription-polymerase chain reaction analysis for AML1-ETO chimeric transcripts showed the presence of the fusion product with the expected size. Translocation (8;21;14)(q22;q22;q24) is a novel variant of t(8;21)(q22;q22), possibly having a common molecular pathogenetic mechanism.
Cancer Genetics and Cytogenetics 02/2002; 132(2):133-5. · 1.39 Impact Factor
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ABSTRACT: The −5 C/T polymorphism of platelet glycoprotein (GP) Ibα is a major determinant of the level of GP Ib/V/IX complex surface expression. We investigated the frequency of this polymorphism among Asian populations. The gene frequencies of cytosine (C) in this polymorphism were 0·283 and 0·219 in Japanese and Korean populations respectively. The C allele is linked with human platelet antigen (HPA)-2a and smaller types of variable number of tandem repeats (VNTR). A novel allele, C-HPA-2a-D of VNTR, was found. No association was observed between these alleles and coronary artery disease in this case–control study. The clinical relevance of this polymorphism in the thrombotic status remains undetermined.
British Journal of Haematology 11/2000; 111(4):1247 - 1249. · 4.94 Impact Factor
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ABSTRACT: The clonal proliferation of large granular lymphocytes can be detected in patients with T-cell-lineage granular lymphocyte-proliferative disorders (T-GLPD) by Southern blotting T-cell receptor genes. However, this cannot be applied to patients with natural killer-cell-lineage GLPD (NK-GLPD) as it lacks a clonal marker. We therefore investigated the use of two other diagnostic techniques in evaluating clonal proliferation in Japanese patients with NK-GLPD (n = 4) and T-GLPD (n=3) by chromosomal analysis of peripheral blood mononuclear cells (PBMC) stimulated with either interleukin-2 or phytohaemaggluti-nin, and Epstein-Barr viral (EBV) genomic DNA analysis. Chromosomal analysis revealed abnormal karyotypes in the PBMC of three of four patients with NK-GLPD, whereas EBV analysis showed a monoclonal terminal configuration in the PBMC in the fourth patient. Southern blots revealed rearrangements of the TCR genes in all three patients with T-GLPD but in none of those with NK-GLPD. It is suggested that these methods may be useful in detecting the abnormal proliferation of large granular lymphocytes in NK-GLPD.
British Journal of Haematology 06/1995; 90(3):578 - 584. · 4.94 Impact Factor
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ABSTRACT: The t(11;14)(ql3;q32) chromosomal translocation is associated with several B-cell lymphoproliferative disorders and is thought to result in upregulation of expression of PRAD1/cyclin D1 protooncogene. A patient with multiple myeloma of IgG κ-type with t(11;14)(q13;q32) is now shown to overexpress PRAD1. The clinical stage of the disease was advanced (IIIA), with a myeloma cell count of 94.6% in the bone marrow. Chromosomal analysis of bone marrow cells showed t(11;14)(q13;q32) in five of 20 metaphases as well as other karyotypic features. Northern blot analysis of RNA prepared from myeloma cells revealed overexpression of PRAD1. Multiple myeloma with t( 11; 14)(q 13;q32) has been associated with an aggressive clinical course. Although neither myeloma cells in the peripheral blood nor extramedullary lesions were apparent in the present patient, the myeloma was refractory to several chemotherapeutic regimens from the beginning. Detection of PRAD1 expression may offer an easier alternative to cytogenetic analysis in myeloma and is a potentially useful indicator of a poor prognosis.
Acta Haematologica. 08/1970; 94(4):199-203.
