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British Journal of Haematology 11/2005; 131(1):1. · 4.94 Impact Factor
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British Journal of Haematology 09/2005; 130(4):467. · 4.94 Impact Factor
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ABSTRACT: Progressive multifocal leukoencephalopathy (PML), a demyelinating infectious disease caused by JC virus (JCV), occurs almost exclusively in immunocompromised patients usually with malignant diseases. We report here a Japanese female with follicular lymphoma who subsequently developed PML. In addition to JCV, human herpesvirus 6 (HHV-6) was detected in the affected brain lesions of the patient by polymerase chain reaction and by in situ hybridization. HHV-6, recognized as a neurotropic virus, is known to be reactivated during immunosuppression and can cause fatal complications such as encephalitis/encephalopathy. It is likely that impaired immunity associated with lymphoma and the additional immunosuppression following cytopenia-inducing chemotherapies predisposed the patient to reactivated HHV-6 infection. Although it remains to be clarified whether HHV-6 plays an important role as a co-agent with JCV in causing demyelination of the brain, our observation alerts physicians to the possible association of HHV-6 with the pathogenesis of PML.
American Journal of Hematology 08/2001; 67(3):200-5. · 4.67 Impact Factor
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ABSTRACT: We describe a family with an inherited constitutional chromosome translocation (3;11) (p21;q23). Of three proven translocation carriers, one had duodenal malignant lymphoma (B-cell diffuse lymphoma, medium-sized cell type). The t(3;11)(p21;q23) was detected not only in hematopoietic cells including the patient's lymphoma cells, non-pathological bone marrow, and phytohemagglutinin-stimulated peripheral blood, but also in fibroblasts of the skin. We have successfully established an Epstein-Barr virus-transformed B-cell line and a Herpesvirus saimiri-transformed T-cell line from the patient, and found that both cell lines also carried this translocation. The patient's asymptomatic mother and sister had the same chromosomal abnormality. Chromosomal abnormalities of the 11q23 band occur frequently in various hematopoietic malignant disorders, and 3q21 has been linked to the pathogenesis of several solid tumors including carcinomas of the kidney, lung, and breast. Although 11q23 is known to recombine with many different chromosomal segments, t(3;11)(p21;q23) has not been reported to our knowledge. Further assessment is warranted to clarify if this constitutional translocation predisposes to certain malignancies. Our cell lines carrying the novel chromosome translocation would be useful for the molecular analysis of the rearranged genes involving both 3p21 and 11q23.
Cancer Genetics and Cytogenetics 03/2000; 117(1):28-31. · 1.39 Impact Factor
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ABSTRACT: Human herpesvirus 6 (HHV-6) genome has been detected in several human lymphoproliferative disorders with no signs of active viral infection, and found to be integrated into chromosomes in some cases. We previously reported a woman with HHV-6-infected Burkitt's lymphoma. Fluorescence in situ hybridization showed that the viral genome was integrated into the long arm of chromosome 22 (22q13). The patient's asymptomatic husband also carried HHV-6 DNA integrated at chromosome locus 1q44. To assess the possibility of chromosomal transmission of HHV-6 DNA, we looked for HHV-6 DNA in the peripheral blood of their daughter. She had HHV-6 DNA on both chromosomes 22q13 and 1q44, identical to the site of viral integration of her mother and father, respectively. The findings suggested that her viral genomes were inherited chromosomally from both parents. The 3 family members were all seropositive for HHV-6, but showed no serological signs of active infection. To confirm the presence of HHV-6 DNA sequences, we performed polymerase chain reaction (PCR) with 7 distinct primer pairs that target different regions of HHV-6. The viral sequences were consistently detected by single-step PCR in all 3 family members. We propose a novel latent form for HHV-6, in which integrated viral genome can be chromosomally transmitted. The possible role of the chromosomally integrated HHV-6 in the pathogenesis of lymphoproliferative diseases remains to be explained.
Blood 10/1999; 94(5):1545-9. · 9.90 Impact Factor
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Yuji Ohtsuki,
Jun Iwata,
Mutsuo Furihata,
Tamotsu Takeuchi,
Hiroshi Sonobe,
Isao Miyoshi,
Y. Ohtsuki,
J. Iwata,
M. Furihata,
T. Takeuchi,
H. Sonobe, I. Miyoshi
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ABSTRACT: The ultrastructure of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) has not yet been fully elucidated, although some findings have been reported using primary effusion lymphoma (PEL) cell lines, KS-1, harboring no Epstein-Barr virus (EBV) coinfection. In the present study, detailed fine structural examination of KSHV/HHV-8 was performed after stimulation of the PEL-derived cell line KS-1 with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in vitro. While unstimulated KS-1 cells contained a small number of intranuclear virus particles associated with no extracellular mature particles, KS-1 cells stimulated with TPA produced many extracellular mature particles as well as intranuclear particles, in addition to interesting tubulo-reticular structures and aggregated tubular structures in vesicles. The induced intranuclear particles were empty, doughnut shaped, and dense cored, with outer and inner diameters of 100-110 nm and 60-70 nm, respectively. Dense-cored extracellular mature particles were 150-160 nm in diameter, and some contained doughnut-shaped cores, together with a few megaloviruses, 260 nm in outer diameter. These findings indicate that KS-1 cells treated with TPA can produce extracellular mature particles as well as intranuclear particles, which were proven to be KSHV/HHV-8.
Medical Electron Microscopy 10/1999; 32(2):94-99.
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The Journal of Infectious Diseases 05/1999; 179(4):1046-7. · 6.41 Impact Factor
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British Journal of Haematology 04/1999; 104(4):934. · 4.94 Impact Factor
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ABSTRACT: The abnormal lymphocytes in adult T cell leukemia (ATL) reveal a peculiar morphology that is characterized by indented or lobulated nuclei. While human T lymphotropic virus type I (HTLV-I) is thought to be integrated in ATL cells, the correlation between the nuclear irregularities and HTLV-I infection is obscure. We have devised a novel single cell polymerase chain reaction (PCR) technique to examine the integration of HTLV-I provirus genome in cells from two patients with ATL. To isolate single cells, peripheral blood smears were prepared on thin polyester slides and stained with May-Grünwald-Giemsa. Morphologically defined single cells were cut out after light microscopy. The HTLV-I DNA sequences were detected not only in ATL cells but also in normal-looking lymphocytes. This novel PCR method may provide a valuable tool for understanding the molecular events associated with HTLV-I infection at the single cell level.
Leukemia 11/1998; 12(10):1645-50. · 9.56 Impact Factor
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ABSTRACT: Human herpesvirus 6 (HHV-6) genome has been found in several human lymphoid malignancies, but configuration of the HHV-6 genome has not been well delineated. We established the HHV-6-positive, Epstein-Barr virus-negative Burkitt's lymphoma cell line Katata. In this study we investigated the status of the HHV-6 genome in Katata cells. Neither linear nor circular HHV-6 DNA was detected by Gardella gel analysis. The fluorescence in situ hybridization technique enabled us to directly visualize the integrated HHV-6 DNA at the single-cell level. Only one integrated site of viral DNA was detected in metaphase chromosomes and it was preferentially located at the long arm of chromosome 22 (22q13). Treatment of the cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or with calcium ionophore A23187 led to induction of the HHV-6 immediate-early gene as well as the late gene. Sodium n-butyrate also gave rise to expression of the HHV-6 genes. The TPA inducibility was synergistically enhanced when combined with A23187 or n-butyrate. Our study provides, for the first time, an in vitro model system of latent HHV-6 infection whose genome is integrated into host DNA of lymphoma cells.
British Journal of Haematology 10/1998; 102(5):1307-13. · 4.94 Impact Factor
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The Lancet 09/1998; 352(9127):543-4. · 38.28 Impact Factor
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ABSTRACT: A male patient with a secondary acute monocytic leukemia whose leukemia cells had a t(10;11)(p13;q13) chromosomal abnormality is described. Gene analysis disclosed that the patient's leukemia cells had MLL gene rearrangement. His leukemia cells responded poorly to chemotherapy, and the patient developed an unusual aggressive leukemia cutis. A t(10;11)(p13;q13) chromosomal abnormality that expresses MLL gene rearrangement has not been reported previously in secondary leukemia.
Cancer Genetics and Cytogenetics 08/1998; 104(1):28-31. · 1.39 Impact Factor
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Leukemia 07/1998; 12(6):1002-4. · 9.56 Impact Factor
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ABSTRACT: To determine the association between leprosy and HTLV-I, 450 and 394 leprosy patients in two sanatoriums in Japan (Sanatorium-A in Okayama prefecture and Sanatorium-B in Gunma prefecture) were investigated serologically for antibodies to HTLV-I. Serology was positive for HTLV-I in 38 (8.4%) of 450 leprosy patients in Sanatorium-A and in 34 (8.6%) of 394 patients in Sanatorium-B. Prevalence was much higher than that in the general population of these areas in Japan. A large proportion of HTLV-I-positive patients in both sanatoriums came from HTLV-I nonendemic areas in Japan, suggesting that HTLV-I infection occurred after the patients arrived at the sanatoriums. Infection through sexual contact or reuse of needles for frequent vaccination are possible routes of infection for HTLV-I in these cases.
Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 04/1998; 17(4):380-3.
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British Journal of Haematology 03/1998; 100(4):802-3. · 4.94 Impact Factor
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ABSTRACT: A total of 34 leukemia and lymphoma samples (17 clinical samples and 17 cell lines) were analyzed for mutations of the Smad2 gene by reverse transcriptase-polymerase chain reaction single strand conformation polymorphism (RT-PCR-SSCP) analysis. Nine of the 34 samples had 18q chromosomal abnormalities. No shifted bands were detected in any of the hematological malignancies. Our results suggest that resistance to cell growth inhibitory effects of TGF-beta in hematological malignancies is not due to alterations of the Smad2 gene.
Leukemia 02/1998; 12(1):94-5. · 9.56 Impact Factor
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British Journal of Haematology 10/1997; 98(4):1048-9. · 4.94 Impact Factor
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ABSTRACT: Human herpesvirus 6 (HHV-6) DNA has been detected in several human lymphoproliferative disorders. We report a case of HHV-6-infected Burkitt's lymphoma, from which a cell line, designated Katata, has been established. Katata cells had an immature B-cell phenotype with an L3 morphology and carried a t(8;14)(q24;q32) chromosomal abnormality. The HHV-6 DNA sequences were detected in both the patient's tumor cells and Katata cell line by polymerase chain reaction using three sets of primers that target different regions of HHV-6 DNA. The presence of HHV-6 DNA in Katata cells was also shown by Southern blot hybridization with the BamHI fragment of HHV-6. It is likely that the virus is in a latent state, since (1) virion-associated protein was not expressed in Katata cells, (2) transcriptional level of the immediate-early gene was very low, and (3) no viral particles were observed by electron microscopy. Katata cells were highly tumorigenic in nude mice and the tumor cells also contained HHV-6 DNA. We have successfully obtained several clonal lines by allowing the cells to form colonies in soft agarose and by the limiting dilution method. HHV-6 DNA was detectable in all 13 clones analyzed, suggesting that virtually all Katata cells are infected with HHV-6. This is the first report of a case of HHV-6+ Burkitt's lymphoma in the absence of Epstein-Barr virus. Furthermore, there has been no report of lymphoma cell lines that are persistently and nonproductively infected with HHV-6. The Katata Burkitt's lymphoma cell line, therefore, would provide a useful tool for studies of the mechanisms of HHV-6 latency and reactivation.
Blood 09/1997; 90(3):1200-7. · 9.90 Impact Factor
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ABSTRACT: We report a 53-year-old-man with an aggressive Ki-1 lymphoma who had high serum CA125, a marker protein of the epithelial ovarian cancer, and interleukin-6 (IL-6) concentrations. Both CA125 and IL-6 levels decreased after chemotherapy and elevated with disease progression. The patient's lymphoma cells obtained before chemotherapy grew continuously in vitro, were IL-6 dependent and were found to secrete CA125 in culture medium. These results indicate that CA125 can be secreted by Ki-1 lymphoma cells and IL-6 may promote the growth of Ki-1 lymphoma cells.
British Journal of Haematology 09/1997; 98(2):450-2. · 4.94 Impact Factor
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ABSTRACT: We report a long-term (14-year) follow-up of a human T-lymphotropic virus type I (HTLV-I)-infected male who was successively afflicted with Graves' disease followed by uveitis. HTLV-I proviral DNA was detected by polymerase chain reaction in the thyroid tissue and HTLV-I was isolated from thyroid tissue by coculture with peripheral blood lymphocytes from an HTLV-I-uninfected healthy female. This case study supports a close relationship between Graves' disease and uveitis in an HTLV-I carrier.
International Journal of Hematology 09/1997; 66(2):233-7. · 1.27 Impact Factor
