Publications by authors named "Akitoshi Nagasaki"

30 Publications

  • Page 1 of 1

[Cauda equina relapse after autologous stem cell transplantation in a patient with primary plasma cell leukemia].

Gan To Kagaku Ryoho 2010 Apr;37(4):743-6

Department of Endocrinology and Metabolism, Internal Medicine, University of The Ryukyus School of Medicine.

We report a rare case showing involvement with the cauda equina after autologous peripheral blood stem cell transplantation for primary plasma cell leukemia (PCL). A 55-year-old man was diagnosed with PCL(IgA-k type, stage III)in November of 2006. He was treated with VAD chemotherapy consisting of vincristine, doxorubicin, and dexamethasone. After achieving hematological remission, he received tandem high-dose melphalan supported by autologous peripheral blood stem cell transplantation. Five months after his second transplant, he complained of lumbago and bilateral leg pain. M-protein and Bence-Jones protein were not detected in serum or urine. An axial magnetic resonance imaging study revealed enlargement of the cauda equina nerve roots on T-1 weighted image. A sagittal T-1 weighted gadolinium-enhanced imaging study showed hyperintensities along the cauda equina. Leptomeningeal enhancement was also seen below the level of Th6. A cytological examination of the cerebrospinal fluid (CSF) with May-Giemsa stain showed atypical plasma cells. Immunoelectrophoresis of the CSF revealed monoclonal IgA-k type protein. A diagnosis of central nervous system (CNS)relapse was made. The patient died of pneumonia two months after relapse. It should be kept in mind that CNS relapse can occur during hematological remission in patients with multiple myeloma including PCL.
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April 2010

Treatment-related Burkitt's lymphoma: literature review and case report of successful treatment with rituximab monotherapy.

Acta Haematol 2009 29;122(4):211-5. Epub 2009 Oct 29.

Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.

The development of Burkitt's lymphoma (BL) is uncommon in elderly people. Most treatment-related hematological malignancies are of a myeloid lineage. Only a few cases with BL secondary to cancer treatment have been described. We report a rare case of an elderly patient with radiotherapy-related BL. A 71-year-old Japanese man, who had a past history of oropharyngeal cancer treated with local irradiation 15 years ago, presented with a left mandibular mass in December 2004. A partial mandibulectomy disclosed pathological features consistent with BL. Although the patient was initially treated with intensive chemotherapy, the development of complications precluded further anticancer drug treatment. Rituximab was administered once weekly for 5 consecutive weeks, with resolution of the mandibular mass. He remained in remission without further lymphoma treatment for more than 3 years after diagnosis. Rituximab monotherapy should be considered as a therapeutic option for elderly patients with BL.
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http://dx.doi.org/10.1159/000253028DOI Listing
December 2009

[HIV- and HHV-8-negative primary effusion lymphoma-like lymphoma presenting with lymphomatous effusions complicated by cardiac tamponade-a case report].

Gan To Kagaku Ryoho 2009 Jul;36(7):1195-8

Dept. of Endocrinology and Metabolism, Internal Medicine, University of The Ryukyus School of Medicine.

We report a rare case of human immunodeficiency virus (HIV)- and human herpes virus-8 (HHV-8)-negative primary effusion lymphoma (PEL)-like lymphoma presenting with lymphomatous effusions complicated by cardiac tamponade. A 68-year-old woman was hospitalized with generalized weakness in June 2006. Echocardiogram revealed the presence of pericardial effusion and she had the signs of cardiac tamponade. Urgent pericardial drainage relieved her symptoms. Chest computed tomography showed bilateral pleural effusions along with pericardial effusion. Cytologic findings of both effusions were suggestive of malignancies, including malignant lymphoma. Immunocytochemical studies with a panel of antibodies, including CD20 and CD79a, could not provide a definite diagnosis. Flow cytometric analysis of pleural effusion revealed that tumor cells were positive for CD10 and CD19, but negative for CD20, CD23, surface immunoglobulin, and T-cell associated antigens. Clonal rearrangement of the immunoglobulin heavy chain gene was detected by Southern blot analysis. Polymerase chain reaction proved to be negative for HHV-8. The serology test for HIV was negative. After a diagnosis of HHV-8-negative PEL-like lymphoma, she was treated with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone). However, she died of progressive lymphoma 7 months after the diagnosis. PEL-like lymphomas are of B-cell origin. In some cases of PEL-like lymphoma, tumor cells may be negative for representative markers of B-cell phenotype such as CD20 and CD79a.
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July 2009

Intensive chemotherapy for a patient with primary cutaneous diffuse large B-cell lymphoma with Burkitt-like morphology.

Intern Med 2009 16;48(6):475-8. Epub 2009 Mar 16.

Department of Endocrinology and Metabolism, Internal Medicine, University of The Ryukyus School of Medicine, Okinawa.

We report a rare case of primary cutaneous diffuse large B-cell lymphoma (DLBCL) with Burkitt-like morphology. A 54-year-old man presented with multiple subcutaneous tumors. Pathological examination showed morphological features resembling Burkitt or Burkitt-like lymphoma (BL/BLL) with high MIB-1 positivity. Cytogenetic studies revealed no 8q24/c-myc translocation. After the diagnosis of Burkitt-like DLBCL, the patient was treated with CODOX-M chemotherapy (cyclophosphamide, doxorubicin, vincristine, cytarabine and methotrexate), which led to durable remission. The present case suggests that short-term, high-intensity chemotherapy used for BL/BLL may be appropriate for primary cutaneous Burkitt-like DLBCL, as well as systemic lymphoma with Burkitt-like morphology.
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http://dx.doi.org/10.2169/internalmedicine.48.1791DOI Listing
August 2009

Extranodal adult T-cell leukemia/lymphoma of the head and neck: a clinicopathological study of nine cases and a review of the literature.

Leuk Lymphoma 2009 Feb;50(2):187-95

Department of Endocrinology and Metabolism, Internal Medicine, University of The Ryukyus School of Medicine, Okinawa, Japan.

Extranodal adult T-cell leukemia/lymphoma (ATLL) of the head and neck is a rare disease. We studied the clinicopathological features of nine patients with ATLL involving extranodal head and neck sites and conducted a literature review. Six patients presented with extranodal mass of the head and neck, whereas three had disseminated diseases. Tumors involved the parotid gland, sinonasal tract, masseter muscle, mandible and skull. Histopathology included diffuse pleomorphic-type (with angiocentric features), Hodgkin-like and anaplastic large cell-type. Five patients with localised disease showed prolonged survival regardless of unfavourable histology and/or aberrant provirus status, including integration of multiple copies or defective provirus. Patients with localised disease documented in the literature, including our study series, had a reduced frequency of elevated lactate dehydrogenase, no hypercalcemia and longer survival. ATLL should be included in the differential diagnosis of extranodal head and neck lymphoma. Localised extranodal ATLL of the head and neck may exhibit indolent clinical behaviours.
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http://dx.doi.org/10.1080/10428190802702383DOI Listing
February 2009

Ras-mediated up-regulation of survivin expression in cytokine-dependent murine pro-B lymphocytic cells.

Tohoku J Exp Med 2008 Sep;216(1):25-34

Department of Endocrinology and Metabolism, University of the Ryukyus, School of Medicine, Okinawa, Japan.

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, has been widely studied because of its aberrant expression in human cancer. Survivin has multiple functions, including cell-cycle regulation at mitosis, inhibition of apoptosis and caspase-independent cytoprotection. Clinical studies have shown that survivin is associated with resistance to treatment and its expression is linked to poor prognosis. Recent studies indicated that Ras pathways up-regulate survivin expression in hematopoietic cells. Here we analyzed downstream pathways of Ras in interleukin-3 (IL-3)-dependent Baf-3 murine-derived pro-B lymphocytic cells that express constitutively active Ras mutants, using signaling pathway-specific inhibitors. Both mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways are involved in the induction of survivin. Downstream of PI3-K, the signaling pathway is composed of two kinases, Akt and mammalian target of rapamycin (mTOR) pathways. In the downstream targets of PI3-K, mTOR but not Akt is responsible for survivin expression. Using a counterflow centrifugal elutriator, we observed G2/M phase-dominant survivin expression in Baf-3 cells. Interestingly, constitutively active Ras mutants also induced survivin in a cell cycle-dependent manner. Reporter assays of the survivin gene promoter revealed a transcriptional regulatory cis-acting region that is responsible for Ras signaling, indicating that Ras increases the transcription of the survivin gene through specific enhancer elements. These data illustrate the pathways regulating survivin expression by Ras. Ras activates the MAPK, PI3-K and mTOR pathways, and these signals enhance survivin transcription. Our data will provide the new information about mechanisms of survivin expression by Ras-signalling pathways.
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http://dx.doi.org/10.1620/tjem.216.25DOI Listing
September 2008

[A Japanese case of human herpes virus-8-associated multicentric castleman disease complicated by hemophagocytic syndrome].

Gan To Kagaku Ryoho 2008 Aug;35(8):1431-4

Dept. of Endocrinology and Metabolism, Internal Medicine, University of The Ryukyus School of Medicine.

We report a Japanese case of human herpes virus-8 (HHV-8)-associated multicentric Castleman disease(MCD) complicated by hemophagocytic syndrome(HPS). A 60-year-old man presented with persistent fever and progressive pancytopenia in June 2004. On physical examination, anemia, icterus, hepatosplenomegaly, and generalized lymphadenopathy were detected. Laboratory findings showed elevated levels of serum ferritin and soluble interleukin-2 receptor. Anti-human immunodeficiency virus (HIV) antibody was negative. Bone marrow aspiration revealed a normocellular marrow with an increased number of hemophagocytic histiocytes. Biopsy of cervical lymph node disclosed pathological features compatible with the plasmablastic variant of Castleman disease. HHV-8 DNA was detected in the specimen from lymph node by polymerase chain reaction. Thus, the diagnosis of HHV-8-associated MCD complicated by HPS was made. The patient was treated with immunotherapy and subsequent chemotherapy. However, he died of bacterial sepsis after one-month therapy. This case report provides some evidence that HHV-8 may be a causative agent of MCD even in HIV-seronegative Japanese patients.
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August 2008

[Primary diffuse large B-cell lymphoma of the uterine cervix--a case report].

Gan To Kagaku Ryoho 2008 Aug;35(8):1423-5

Dept. of Endocrinology and Metabolism, Internal Medicine, University of The Ryukyus School of Medicine.

Primary malignant lymphoma of the female genital tract is an extremely rare clinical entity. We report a case of primary non-Hodgkin lymphoma of the uterine cervix. A 68-year-old woman presented with abnormal genital bleeding in May 2002. A coloposcopic examination revealed a mass in the uterine cervix. Magnetic resonance imaging showed a bulky cervical tumor(7.5 x 8 cm)invading the right parametrium and adjacent levator ani muscle. Involvement of pelvic lymph nodes was also observed. The uterine lesion exhibited homogenous hypointensity on T1 weight image and isointense to hyperintense on T2-weight image. No other lesions were detected by the whole-body computed tomography, gallium scintigraphy, and bone marrow examination. Although cytology of the smear from the uterine cervix was nondiagnostic, the histologic examination of the punch biopsy material showed a diffuse proliferation of atypical lymphoid cells. Immunophenotypic studies revealed tumor cells were positive for CD19, CD20, CD30, and k-chain. A diagnosis of diffuse large B-cell lymphoma of the uterine cervix, clinical stage IIE was made. The patient was treated with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone(CHOP)chemotherapy followed by the involved field irradiation. She remains alive and free of disease more than 5 years after the diagnosis.
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August 2008

[Primary pulmonary Hodgkin lymphoma--two case reports and a review of the literature].

Gan To Kagaku Ryoho 2007 Dec;34(13):2279-82

Dept. of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine.

Primary extranodal involvement of Hodgkin lymphoma (HL) is rare. We report two HL patients presenting with exclusive or predominant lung involvement. In both cases, the results of transbronchial and/or CT-guided lung needle biopsy were indicative of granulomatous disease. Eventually, lymph node biopsy specimens revealed HL with nodular sclerosis type and lymphocyte-rich type, respectively. There were no specific symptoms, laboratory and imaging findings for pulmonary HL. A histological examination was required to confirm the diagnosis. Lung biopsy techniques such as transbronchial or percutaneous biopsy may be insufficient to allow diagnosis of HL. Pulmonary HL should be included in the differential diagnosis of lung involvement, even when the pathological evaluation of nonspecific inflammation was made from the biopsied specimens.
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December 2007

Sinonasal zygomycosis in a patient with myelodysplastic syndrome following non-myeloablative allogeneic peripheral blood stem cell transplantation.

Intern Med 2007 16;46(22):1881-2. Epub 2007 Nov 16.

Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine, Okinawa.

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http://dx.doi.org/10.2169/internalmedicine.46.0069DOI Listing
December 2007

Adult T-cell leukemia/lymphoma with multiple integration of HTLV-1 provirus presenting as an isolated paranasal sinus tumor: a case report.

Head Neck 2008 Jun;30(6):815-20

Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.

Background: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoma and etiologically associated with human T-lymphotropic virus type 1 (HTLV-1). Patients with ATLL commonly present with leukemic changes, systemic lymphadenopathy, and/or extranodal lesion and have very poor prognosis.

Methods And Results: We describe a rare case of ATLL presenting as an isolated paranasal mass. Southern blot analysis of the biopsied specimens demonstrated multiple integration bands of HTLV-1 provirus of different intensities. Chemotherapy resulted in complete resolution of the paranasal mass. Thereafter, the patient showed an indolent clinical course with leukemic changes and pulmonary and cutaneous ATLL lesions and remains alive more than 5 years from diagnosis.

Conclusion: ATLL should be included in the differential diagnosis of sinonasal lymphoma, although the event is rare. Multiple HTLV-1 provirus integrations of different intensities may be indicative of good prognosis for ATLL.
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http://dx.doi.org/10.1002/hed.20730DOI Listing
June 2008

Primary adrenal adult T-cell leukemia/lymphoma: a case report and review of the literature.

Am J Hematol 2007 Aug;82(8):748-52

Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.

Primary adrenal lymphoma (PAL) is very rare; the majority of cases reported previously were of B-cell origin. We report a rare case of primary adrenal adult T-cell leukemia/lymphoma (primary adrenal ATLL). ATLL is a highly aggressive T-cell type non-Hodgkin's lymphoma and etiologically associated with human T-cell lymphotropic virus 1 (HTLV-1). Most ATLL patients present with leukemia and widespread lymphadenopathy. A 37-year-old Japanese woman presented with back pain in January 2004. Examination showed no peripheral lymphadenopathy, circulating lymphoma cells, hepatosplenomegaly, and skin lesions. Imaging studies demonstrated large adrenal masses bilaterally. Subsequently, she underwent open adrenal biopsy and pathological diagnosis was confirmed as T-cell lymphoma. The serum antibody to HTLV-1 was positive. Southern blot analysis detected monoclonal integration of proviral DNA of HTLV-1 into host genome in the biopsy specimen. The diagnosis of ATLL arising in adrenal glands was established. Despite repeated systemic chemotherapy, the patient died of progressive disease in December 2004. ATLL could primarily involve the adrenal gland and this disease entity should be included in the differential diagnosis of adrenal mass lesions.
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http://dx.doi.org/10.1002/ajh.20856DOI Listing
August 2007

Establishment of a human herpes virus-8-negative malignant effusion lymphoma cell line (STR-428) carrying concurrent translocations of BCL2 and c-MYC genes.

Leuk Res 2007 Sep 21;31(9):1285-92. Epub 2007 Mar 21.

Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.

A new cell line, STR-428 was established from ascites tumor cells of a malignant effusion lymphoma patient without human herpes virus-8 (HHV-8) infection. STR-428 cells showed an immunophenotype of mature B-cells and produced few cytokines related to lymphomatous effusion. Karyotypic and genetic analysis revealed complex translocations including t(14;18)(q32;q21) effecting IgH/BCL2 and der(8)t(3;8)(q27;q24) involving c-MYC. STR-428 represents a unique, B-cell lymphoma cell line carrying concurrent rearrangement of BCL2 and c-MYC genes with features distinct from those of HHV-8-related primary effusion lymphoma. This cell line may be a valuable tool, other than HHV-8, to investigate the pathogenesis of primary lymphomatous effusion.
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http://dx.doi.org/10.1016/j.leukres.2006.12.023DOI Listing
September 2007

[Interdigitating dendritic cell sarcoma/tumor--a case report].

Gan To Kagaku Ryoho 2007 Mar;34(3):469-71

Dept. of Endocrinology and Metabolism, University of The Ryukyus School of Medicine.

We report an extremely rare case of interdigitating dendritic cell sarcoma/tumor (IDCS). A 52-year-old man presented with a 2-week history of fever in January 2002. Physical examination revealed enlarged, painless right axillary lymph nodes, and hepatosplenomegaly. Whole-body computerized tomography showed enlarged lymph nodes in mediastinal, right axillary, abdominal para-aortic, ileum, and inguinal regions. Hepatosplenomegaly was also detected. In addition to abnormal liver function tests, serum levels of soluble interleukin-2 receptor and ferritin were elevated. Excisional biopsy of right axillary lymph node was performed in February 2002. Histological examination showed a diffuse proliferation of medium-to large-sized cells with round or oval nuclei and abundant cytoplasm. Spindle shape cells and Hodgkin-like giant cells were also seen. Immunohistochemically, the tumor cells expressed S-100 protein, CD 68, and CD 45 RO. They were negative for CD 1, CD 3, CD 15, CD 20, CD 21, CD 23, FDC, DRC, and p80. These findings were compatible with the diagnosis of IDCS. The patient was treated with polychemotherapy consisting of doxorubicin,cyclophosphamide, vincristine, and prednisone. However, he developed fungal pneumonia and died of respiratory failure 1 month after the start of treatment.
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March 2007

Air-leak syndrome associated with bronchiolitis obliterans after allogeneic peripheral blood stem cell transplantation.

Int J Hematol 2007 Feb;85(2):95-6

Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.

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http://dx.doi.org/10.1532/IJH97.06184DOI Listing
February 2007

[Development of acute type, CD 8 positive adult T-cell leukemia in a carrier of hepatitis B virus--possible therapeutic effect of lamivudine combined with chemotherapy].

Gan To Kagaku Ryoho 2006 May;33(5):683-6

Dept. of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus.

Cases of adult T-cell leukemia (ATL) with aberrant phenotypes have a very poor prognosis. We report the development of acute type, CD 8 positive ATL in a carrier of hepatitis B virus (HBV). The patient was treated with a combination of lamivudine and chemotherapy and consequently had longer-term survival than those reported previously. A 64-year-old(corrected 65-year-old) man was referred to our hospital in January 2002 because of ascites and abdominal tumor. He was positive for anti-HTLV-1 antibody and HBV surface antigen. Generalized computed tomography demonstrated bilateral pleural effusion, abdominal mass, and massive ascites. Cytological examination of ascitis revealed numerous atypical lymphoid cells,which were positive for CD 2, CD 5, CD 8, and CD 25. Monoclonal integration of HTLV-1 provirus was detected by Southern blot analysis on DNA extracted from lymphoid cells. A diagnosis of acute type, CD 8 positive ATL was made. Lamivudine was administered for prevention of chemotherapy induced HBV reactivation. Subsequently, he was treated with 6 cycles of CHOP and went into remission. He maintained clinical remission during a follow-up of 13 months and then relapsed. Further salvage therapies were provided with a transient effect. He died of sepsis in February 2004. The overall survival time of this patient was 25 months. It is possible that lamivudine combined with chemotherapy may have had a therapeutic effect on ATL in this case.
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May 2006

Cardiac involvement of lung cancer presenting with acute myocardial infarction-like electrocardiographic changes.

Intern Med 2006 15;45(2):113-4. Epub 2006 Feb 15.

Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine, Okinawa.

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http://dx.doi.org/10.2169/internalmedicine.45.1559DOI Listing
July 2006

Very late central nervous system relapse in a patient with B cell lymphoblastic lymphoma.

Acta Haematol 2004 ;112(4):212-6

Second Department of Internal Medicine, Faculty of Medicine, University of The Ryukyus, Okinawa, Japan.

Very late relapse of lymphoblastic lymphoma (LBL) is very rare. We report a case of a patient who developed central nervous system (CNS) relapse of LBL 16 years after the onset of the primary disease. An 8-year-old girl was hospitalized with a skin tumor in the occipital region on November 27, 1984. Examination of a biopsy of the skin tumor showed typical features of non-Hodgkin's lymphoma (diffuse medium-sized cell type). She received multiagent chemotherapy and went into remission. On July 4, 2000, she was hospitalized with persistent headache. Cranial magnetic resonance imaging showed a cerebellar lesion, which was hypointense on T1-weighted images and of heterogeneous intensity on T2-weighted images. A midline suboccipital craniotomy was performed and pathological examination revealed a diffuse proliferation of lymphoid cells, which were positive for terminal deoxynucleotidyl transferase, but negative for CD45RO, CD3 and CD20. Tumor cells stained positively for CD10, CD22, CD38 and HLA-DR. Revised immunohistochemistry of the primary specimens of skin tumor obtained 16 years earlier revealed a phenotype similar to that of the CNS disease. Polymerase chain reaction products for the immunoglobulin gene from both the skin and cerebellar specimens were an identical size. Thus, the original diagnosis of diffuse medium-sized lymphoma was revised to B cell LBL. An isolated CNS relapse of LBL was apparent in the present case. After salvage chemotherapy, the patient underwent high-dose chemotherapy with autologous peripheral blood stem cell support and subsequent craniospinal irradiation. She went into a lasting complete remission.
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http://dx.doi.org/10.1159/000081275DOI Listing
December 2004

Primary malignant lymphoma of bone marrow.

Intern Med 2004 Jun;43(6):524-5

Second Department of Internal Medicine, Faculty of Medicine, University of Ryukyus, Okinawa.

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http://dx.doi.org/10.2169/internalmedicine.43.524DOI Listing
June 2004

Signet-ring cell lymphoma.

Intern Med 2003 Oct;42(10):1055-6

Second Department of Internal Medicine, Faculty of Medicine, University of Ryukyus, Nakagami-gun, Okinawa.

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http://dx.doi.org/10.2169/internalmedicine.42.1055DOI Listing
October 2003

Emergence of secondary acute lymphoblastic leukemia of Burkitt type after treatment of rhabdomyosarcoma.

Med Pediatr Oncol 2003 Nov;41(5):471-2

Second Department of Internal Medicine, Faculty of Medicine, University of The Ryukyus, Okinawa, Japan.

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http://dx.doi.org/10.1002/mpo.10414DOI Listing
November 2003

[A case of primary malignant lymphoma of the duodenum successfully treated with dose escalating chemotherapy].

Gan To Kagaku Ryoho 2003 Aug;30(8):1169-73

2nd Dept. of Internal Medicine, Faculty of Medicine, University of the Ryukyus.

A 65-year-old woman with diabetes mellitus was hospitalized for heart failure and anemia in August 2001, and recovered with conservative treatment. An endoscopic examination revealed an ulcerative mass located in the duodenal bulb to the 2nd portion. Abdominal CT scan demonstrated tumor involvement in the pancreas head. The diagnosis of a diffuse large B-cell lymphoma, clinical stage IIE, was made by endoscopic biopsy. Although surgical resection of the localized intestinal tumor would have been a common choice for initial treatment, polychemotherapy was selected; the patient had diabetes mellitus and preferred polychemotherapy to surgical operation. Because of bulky intestinal mass, transmural disease and sensitive histological type, standard-dose chemotherapy was considered to include a high risk of intestinal perforation. We performed dose-escalating chemotherapy: A half dose of THP-COP (pirarubicin, cyclophosphamide, vincristine) was given at the start in October 2001, 60% THP-COP as the next cycle, 80% THP-COP as the 3rd cycle and thereafter. Without serious complications of the intestine, she received a total of 6 cycles of chemotherapy and subsequent involved field radiation. There has been no evidence of recurrence of disease 14 months from the start of chemotherapy. When conditions make surgical treatment difficult, dose-escalating chemotherapy in a treatment cycle may be considered as an alternative.
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August 2003

Reversible posterior leukoencephalopathy syndrome associated with tacrolimus therapy.

Intern Med 2003 Jul;42(7):624-5

The Second Department of Internal Medicine, Faculty of Medicine, The University of Ryukyus, Nakagami-gun, Okinawa.

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http://dx.doi.org/10.2169/internalmedicine.42.624DOI Listing
July 2003

Recurrent mutation Trp126 --> stop of glycoprotein IX in Japanese Bernard-Soulier syndrome.

Platelets 2003 May;14(3):197-8

Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukus, Okinawa, Japan.

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http://dx.doi.org/10.1080/0953710031000092848DOI Listing
May 2003

A nitric oxide synthase inhibitor, N(G)-nitro-l-arginine-methyl-ester, exerts potent antiangiogenic effects on plasmacytoma in a newly established multiple myeloma severe combined immunodeficient mouse model.

Br J Haematol 2003 Feb;120(3):396-404

Department of Internal Medicine II, Kumamoto University School of Medicine, Kumamoto, Japan.

Angiogenesis is one of critical factors in sustaining the growth, invasion and metastasis of certain solid tumours and haematological malignancies such as multiple myeloma (MM). In the present study, we examined the anticancer potential of an inhibitor of nitric oxide synthase (NOS), NG-nitro-l-arginine methyl ester (L-NAME), in a novel severe combined immunodeficient mouse model (KHM mouse) that harbours the highly sanguineous plasmacytoma cell line KHM-4, derived from a patient with highly chemoresistant MM. KHM mice were intraperitoneally administered with either L-NAME, doxorubicin, melphalan, or paclitaxel. A significant reduction in tumour sizes was noted in L-NAME-administered KHM mice while no significant reduction was observed in melphalan- or doxorubicin-administered mice. A profound decrease in angiogenesis was observed in tumour tissues from L-NAME- and paclitaxel-administered KHM mice. A marked decrease in human vascular endothelial cell growth factor (VEGF) levels was identified in tumour tissues from L-NAME-administered KHM mice, strongly suggesting that L-NAME suppressed VEGF production by tumour cells through its inhibition of NOS in tumour cells, resulting in reduced neovasculization in mice leading to the regression of tumour sizes. The present data represent the first observations that certain NOS inhibitors potentially serve as experimental agents for the treatment of chemoresistant MM and plasmacytoma.
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http://dx.doi.org/10.1046/j.1365-2141.2003.04078.xDOI Listing
February 2003

Acute myeloid leukemia (FAB-M2) with a masked type of t(8;21) translocation revealed by spectral karyotyping.

Int J Hematol 2002 Nov;76(4):338-43

We report a case of acute myeloid leukemia (AML), M2 subtype according to the French-American-British (FAB) classification, with extramedullary myeloblastoma of the uterus and a masked type of variant translocation of t(8;21)(q22;q22). A 45-year-old Japanese woman presented with metrorrhagia, and AML (M2) with uterine invasion was diagnosed. The patient received an allogeneic peripheral blood stem cell transplantation after remission, and her pelvis was irradiated locally. Cytogenetic study at first showed t(8;17)(q22;p13) by G-banding. Spectral karyotyping (SKY) analysis modified this interpretation to a 3-way translocation involving chromosomes 8,17, and 21 and identified a masked type of variant t(8;21)(q22;q22) translocation. Results of fluorescence in situ hybridization using the AML1/ETO probe, and of detection of the AML1/ETO fusion transcript by reverse transcriptase-polymerase chain reaction were consistent with the karyotyping result. SKY analysis is useful to compensate for the limitations of cytogenetic studies.
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http://dx.doi.org/10.1007/BF02982693DOI Listing
November 2002

Establishment of a primary effusion lymphoma cell line (RM-P1) and in vivo growth system using SCID mice.

Int J Hematol 2002 Aug;76(2):165-72

Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukus, Nishihara, Okinawa, Japan.

Primary effusion lymphoma (PEL) is recognized as a unique lymphoma entity, which occurs exclusively in body cavities as a serous lymphomatous effusion without tumor formation or organ infiltration. We established a cell line of B-cell origin from a pericardial effusion of a 63-year-old Japanese PEL patient who did not have human immunodeficiency virus infection. This PEL cell line had human herpesvirus-8 (HHV-8) and Epstein-Barr virus (EBV) infection. We named this cell line RM-P1. This cell line showed complex chromosomal abnormalities that could not be identified by G-banding. However, spectral karyotyping analysis determined the origin and organization of all unidentified chromosomal abnormalities. When inoculated into the peritoneal cavity of 8 severe combined immunodeficiency (SCID) mice depleted of natural killer cells, RM-P1 cells induced solid tumor with ascites in all animals tested. These tumor and ascitic cells had the same immunogenotypic features as those of the original RM-P1. These 2 types of cells were positive for both HHV-8 and EBV as demonstrated using polymerase chain reaction. Fluorescence-activated cell sorting analyses showed that neither tumors nor ascitic cells grown in SCID mice expressed leukocyte function-associated antigen (LFA)-1alpha (CD11a), LFA-1lbeta (CD18), LFA-2 (CD2), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), ICAM-2 (CD102), ICAM-3 (CD50), or leukocyte endothelial adhesion molecule (LECAM)-1 (CD62L), suggesting that these cytoadhesion molecules are not involved in tumor formation of RM-P1 cells in vivo. The establishment of the RM-P1 cell line and the animal model of PEL may provide insights for understanding the relationship between these viruses and PEL and for understand the mechanism for PEL.
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http://dx.doi.org/10.1007/BF02982580DOI Listing
August 2002
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