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Biomedical subjects

M Tanimoto

Publications and source records attributed to M Tanimoto.

At least 37 records · Page 2Linked to original sources
PubMed2002

Cyclic thrombocytopenia and polycythemia vera.

A periodic fall of platelet number characterizes an acquired pathological condition named cyclic thrombocytopenia. We describe an unusual case of polycythemia vera in which the episodes of thrombocytopenia were followed regularly by thrombocytosis. The period of platelet count fluctuation was about 50 days, with the counts ranging from 34 to 820 x 10(9)/l. Bone marrow megakaryocytes were decreased in number during platelet nadir. Circulating thrombopoietin levels fluctuated out of phase with the platelet count. We suggest that at least some cases of polycythemia vera may have an unstable hematopoietic stem cell pool in nature, which could contribute to the development of unprovoked cyclic thrombocytopenia.

Aged↗
PubMed2002

CP violation in neutrino oscillation and leptogenesis.

We study the correlation between CP violation in neutrino oscillations and leptogenesis in the framework with two heavy Majorana neutrinos and three light neutrinos. Among three unremovable CP phases, a heavy Majorana phase contributes to leptogenesis. We show how the heavy Majorana phase contributes to Jarlskog determinant J as well as neutrinoless double beta decay by identifying a low energy CP-violating phase which signals the CP-violating phase for leptogenesis. For some specific cases of the Dirac mass term of neutrinos, a direct relation between lepton number asymmetry and J is obtained. We also study the effect coming from the phases which are not related to leptogenesis.

Journal Article↗
PubMed2002

Fournier's gangrene after unrelated cord blood stem cell transplantation.

A 16-year-old boy with refractory acute myelogenous leukemia developed Fournier's gangrene as an early complication after two-antigen HLA-mismatched unrelated cord blood stem cell transplantation. On day 25 after the transplantation, he noted abrupt onset of penile swelling with miction pain. The penile inflammation rapidly extended posteriorly to involve the scrotum and perianal tissues, inferiorly to involve the thighs, and superiorly up the lower abdominal region within the next 36 h, and he died from sepsis on day 27. Fournier's gangrene presenting as a genitoperineal necrotizing fasciitis should be considered as a potential complication in umbilical-cord blood recipients in the cytopenic post-transplant phase.

Adolescent↗
PubMed2002

Bilateral adrenal hemorrhage in essential thrombocythemia.

A 67-year-old woman with previously untreated essential thrombocythemia developed bilateral adrenal hemorrhage. She had no known vascular risk factors including smoking, diabetes mellitus, hypertension, and hypercholesterolemia. Her platelet count was 921 x 10(9)/l. She received preemptive steroid therapy to prevent the occurrence of adrenal crisis, but 5 weeks later the replacement therapy was discontinued because the patient fully recovered with a normal adrenocorticotropic hormone stimulation test. Thereafter, she remained well for more than 4 years with a platelet count ranging from 600 to 800 x 10(9)/l. Although adrenal hemorrhage is very rare, it can occur as a hemorrhagic complication of essential thrombocythemia.

Adrenal Gland Diseases↗
PubMed2002

Quantitative analysis of NF-kappaB-expression in cartilage and synovium of rat knee induced by intra-articular injection of synthetic lipid A.

OBJECTIVE: NF-kappaB expression in cartilage and synovium of rat knee after intra-articular injection of lipid A was investigated. METHODS: Inflammation was evaluated in histological sections stained with hematoxylin and eosin, toluidine blue and immunostained with monoclonal anti-NF-kappaB antibody or monoclonal anti-TNF-alpha antibody. RESULTS: Inflammatory cell infiltration into the synovium, hyperplasia of synovial lining layers, loss of metachromasia of cartilage, TNF-alpha-positive cells and NF-kappaB-positive cells in the synovium and cartilage were observed in all 26 rat knees intra-articularly injected with lipid A. The numbers of TNF-alpha-positive and NF-kappaB-positive synovial cells and chondrocytes after the injection were significantly greater than those in knees injected with triethylamine (p < 0.05). The amount of inflammatory cell infiltration into the synovium, synovial lining layers, TNF-alpha-positive synovial cells and NF-kappaB-positive synovial cells 12 h after the injection was significantly smaller than those after 1 day (p < 0.05). CONCLUSION: Intra-articular injection of lipid A induced NF-kappaB expression in cartilage and synovium. Cartilage degeneration started earlier than synovitis in this model. Quantitative analysis of NF-kappaB in cartilage might be useful to evaluate the extreme acute phase of cartilage degeneration.

Animals↗
PubMed2002

Clonal expansion of limited T cell clonotypes in affected muscle from a patient with post-transplant polymyositis.

Critical roles of T cells in idiopathic polymyositis have been suggested, but, those in polymyositis occurring as GVHD after BMT are poorly understood. We thus investigated T cell clonality in a patient with post- transplant polymyositis. As a result, T cell receptor beta chains used various BV families in peripheral blood, but only one BV family (BV7) in affected muscle. Importantly, T cells proliferated oligoclonally both in the peripheral blood and the muscle, however, the expanded clonotypes were completely different. Taken together, T cells expanded in the muscle, possibly stimulated by limited kinds of antigens, may drive myositis.

Adult↗
PubMed2002

Reduced effect of gemtuzumab ozogamicin (CMA-676) on P-glycoprotein and/or CD34-positive leukemia cells and its restoration by multidrug resistance modifiers.

Gemtuzumab ozogamicin (CMA-676), a calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, has recently been introduced clinically as a promising drug for the treatment of patients with acute myeloid leukemia (AML), more than 90% of which express CD33 antigen. However, our recent study suggested that CMA-676 was excreted by a multi- drug-resistance (MDR) mechanism in P-glycoprotein (P-gp)-expressing leukemia cell lines. We analyzed the in vitro effects of CMA-676 on leukemia cells from 27 AML patients in relation to the amount of P-gp, MDR-associated protein 1 (MRP1), CD33 and CD34, using a multi-laser-equipped flow cytometer. The cytocidal effect of CMA-676, estimated by the amount of hypodiploid portion on cell cycle, was inversely related to the amount of P-gp estimated by MRK16 monoclonal antibody (P = 0.004), and to the P-gp function assessed by intracellular rhodamine-123 accumulation in the presence of PSC833 or MS209 as a MDR modifier (P = 0.0004 and P = 0.002, respectively). In addition, these MDR modifiers reversed CMA-676 resistance in P-gp-expressing CD33(+) leukemia cells (P = 0.001 with PSC833 and P = 0.0007 with MS209). In CD33(+) AML cells from 13 patients, CMA-676 was less effective on CD33(+)CD34(+) than CD33(+)CD34(-) cells (P = 0.002). PSC833 partially restored the effect of CMA-676 in CD33(+)CD34(+) cells. These results suggest that the combined use of CMA-676 and a MDR modifier will be more effective on CD33(+) AML with P-gp-related MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes.

Although CD4(+) helper T lymphocytes have been demonstrated to play an important role in antitumor immune response, only a few epitopes of tumor-associated antigens recognized by HLA class II-restricted CD4(+) T lymphocytes have been identified. In the present study, we addressed the question of whether leukemia-associated fusion proteins are recognized by CD4(+) T lymphocytes. Immature dendritic cells (DCs) were loaded with necrotic or apoptotic leukemia cells with t(6;9) or t(9;22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4(+) T lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4(+) T lymphocyte clones produced interferon-gamma (IFN-gamma) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6;9) and t(9;22), respectively. IFN-gamma production by CD4(+)T lymphocyte clones in response to stimulation with DCs loaded with leukemia cells was inhibited by the anti-HLA-DR monoclonal antibody. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4(+) T lymphocytes.

Antigen Presentation↗
PubMed2002

Acquired type 3-like von Willebrand syndrome preceded full-blown systemic lupus erythematosus.

We report a quite rare case of acquired type 3-like von Willebrand syndrome (vWS) that preceded full-blown systemic lupus erythematosus (SLE). A 16-year-old woman with no previous disease history and no family history of hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis and gingival bleeding. She was diagnosed as having atypical type 3 von Willebrand disease because of prolonged bleeding time with normal platelet count and prolonged activated partial thromboplastin time (aPTT), and an almost complete absence of von Willebrand factor (vWF) antigen, ristocetin cofactor activity (vWF:RCo) and ristocetin-induced platelet agglutination (RIPA). Furthermore, electrophoretic analysis of plasma vWF revealed a trace amount of vWF and an absence of the multimeric form of vWF. Infusions of either vasopressin or factor VIII/vWF concentrates improved bleeding symptoms and corrected the aPTT and RIPA. However, she complained of low-grade fever, general fatigue and polyarthralgia 5 months later, and leukocytepenia and hypo-complementemia developed. Anti-double-stranded DNA antibodies and lupus erythematosus cells became positive. These findings were compatible with SLE. Mixing the patient's platelet-poor plasma (PPP) with normal platelet-rich plasma (PRP) (PPP/PRP = 2/1) resulted in a complete inhibition of RIPA, suggesting the presence of vWF inhibitor in her plasma. Treatment with prednisolone (40 mg/day) started and the bleeding tendency gradually improved. One month later, all of the laboratory data including aPTT, bleeding time, RIPA and vWF:RCo became normal. These findings indicate that she has an acquired type 3-like vWS associated with SLE.

Adolescent↗
PubMed2002

Life-threatening bleeding and acquired factor V deficiency associated with primary systemic amyloidosis.

Acquired factor X deficiency has been described in patients with amyloidosis but acquired factor V deficiency is quite rare. We report here a case of life-threatening bleeding and acquired factor V deficiency associated with primary amyloidosis. A 50-year-old man who had no previous hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis, gingival bleeding and hemospermia. The laboratory examination revealed that both the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) were significantly prolonged, and factor V activities were markedly decreased to 14-39% of the normal value. Other coagulation factors such as fibrinogen, prothrombin, factor VII, factor VIII, factor IX and factor X were subnormal and normal. Transaminases were slightly elevated but serological tests of hepatitis B and hepatitis C were negative. Mild hepatosplenomegaly was noted without sign of liver cirrhosis. The PT and aPTT obtained 8 years ago when he received a cholecystectomy due to cholecystitis were both normal. Specific assays for the detection of factor V inhibitor were repeatedly performed but no factor V inhibitor was found. Furthermore, a significant recovery of the infused factor V was noted shortly after an intravenous administration of 5-10 U fresh frozen plasma, but it did not last more than 6 h. Melena, bleedings into the left shoulder and buttock, and finally mortal retroperitoneal hemorrhage developed despite repeated infusions of large amounts of fresh frozen plasma. Acquired factor V deficiency associated with primary amyloidosis was suspected but histological diagnosis was not obtained because of the severe bleeding tendency. Autopsy revealed hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart and other parenchymal organs. Perivascular amyloid deposition and factor V deficiency are both thought to be the cause of the severe hemorrhagic tendency seen in this patient.

Amyloidosis↗
PubMed2002

Pneumonitis induced by rifampicin.

An 81-year-old man was admitted to hospital with pulmonary Mycobacterium tuberculosis infection and was treated with rifampicin (RFP), isoniazid (INH), and ethambutol (EB). On day 9 he developed fever and dyspnoea. Chest radiographs showed new infiltration shadows in the right lung. Bronchoalveolar lavage (BAL) was performed and increased numbers of lymphocytes were recovered. Drug induced pneumonitis was suspected so the antituberculous regimen was discontinued and methylprednisolone was administered. The symptoms and infiltration shadows improved. INH and EB were reintroduced without any recurrence of the abnormal shadows. T cell subsets in the BAL fluid and a positive lymphocyte stimulation test for RFP suggest that RFP induced pneumonitis may be related to a complex immunological response.

Aged↗
PubMed2001

Therapy-related myelodysplastic syndrome/acute myeloid leukemia M2 and translocation (8;21).

An 80-year-old woman developed therapy-related myelodysplastic syndrome with translocation (8;21), which was successfully treated with an acute myeloid leukemia oriented chemotherapy. Five years before admission she had received cyclophosphamide, epirubicin, and carboplatin for endometrial cancer. The leukemia cell morphology alerted us to the possibility of the presence of t(8;21) before cytogenetic results were obtained, and AML1/ETO fusion transcript was detected by reverse transcription polymerase chain reaction. She achieved complete remission after one course of idarubicin and cytosine arabinoside. She has remained in complete remission for 6 months. Our experience suggests that recognition of typical morphological features for de novo M2 acute myeloid leukemia with t(8;21) would be important in diagnosis of therapy related myelodysplastic syndrome/acute myeloid leukemia with this translocation, which could respond to an intensive chemotherapy.

Aged↗
PubMed2001

Histone deacetylase 3 associates with and represses the transcription factor GATA-2.

The zinc finger transcription factor GATA-2 plays a critical role in the survival and proliferation of hematopoietic stem cells. This study examined the interaction of GATA-2 with histone deacetylases (HDACs) to define the involvement of HDACs in the regulation of GATA-2 function. GATA-2 directly associates with HDAC3 but not with HDAC1. Consistent with this, HDAC3 suppressed the transcriptional potential of GATA-2, whereas HDAC1 did not affect GATA-2-dependent transcription. Results further demonstrated that GATA-2 and HDAC3 colocalized in the nucleus. These results identify GATA-2 as a nuclear target for HDAC3-mediated repression. Furthermore, GATA-2 also directly associated with HDAC5 but not with other class II HDACs examined, that is, HDAC4 and HDAC6. This is the first demonstration that a tissue-specific transcription factor directly and selectively interacts with HDAC3 and HDAC5 among HDAC family members.

Animals↗
PubMed2001

Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA haplotype loss restricted by the remaining HLA class I allele.

Although loss of HLA expression by malignant cells has also been demonstrated, it has not been clarified how the loss of HLA expression observed in vitro actually results in immune escape. We demonstrated two major findings: (i) a part of chromosome 6 coding for HLA haplotypes was deleted from the genome of chondrosarcoma cell line, OUMS-27; furthermore, immunohistostaining for HLA-A11 showed that the original chondrosarcoma tissue lost the expression of HLA-A11, implicating that HLA haplotype loss was already present in the original tumor tissue and (2) HLA class I-restricted and autologous tumor-specific cytotoxic T cells (CTL) were generated from peripheral blood lymphocytes of the patient with chondrosarcoma, from whom OUMS-27 originated. This CTL line was maintained by weekly stimulation with OUMS-27, and lysed OUMS-27 in an HLA-A24 dependent manner but did not either K562 or autologous (EBV)-transformed B cells. These observations indicated that OUMS-27 and its original tumor are still immunogenic and can present antigen peptides with the remaining HLA-A24, even if HLA expression is partially lost. Tumor specific immunotherapy can be applied to the treatment of malignancies, even if HLA expression is partially lost.

Aged↗
PubMed2001

Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group.

A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg x m(-2) was given first and followed by CPT-11 at a dose of 50 mg x m(-2). Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32-63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities.

Adult↗
PubMed2001

Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12).

The TEL gene on 12p12-13 is a target for a number of translocations associated with various hematological malignancies. The fusion of the TEL gene to the Syk gene in a patient with myelodysplastic syndrome (MDS) with t(9;12)(q22;p12) is reported. Southern blot analysis of patient bone marrow cells with TEL and Syk gene probes detected rearranged fragments. Anchored polymerase chain reaction identified the Syk gene, a nonreceptor tyrosine kinase, on 9q22 fused downstream of TEL exon 5. The TEL gene was fused in-frame to Syk and produced a fusion protein that was constitutively phosphorylated in tyrosine with dimerization that was mediated by the helix-loop-helix domain of TEL. A TEL-Syk fusion product transformed the murine hematopoietic cell line BaF3 to interleukin-3 growth factor independence. TEL-Syk is a novel transforming protein and leads to the transformation of hematopoietic cells. These data implicate that the rearranged Syk gene is involved in the pathogenesis of hematopoietic malignancies.

Amino Acid Sequence↗