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Biomedical subjects

Takahiro Tamura

Publications and source records attributed to Takahiro Tamura.

14 recordsLinked to original sources

Gene therapy with TRAIL against renal cell carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells. However, TRAIL is not toxic against most normal cells. We have accordingly examined by in vivo electroporation whether TRAIL induces apoptosis in renal cell carcinoma. In addition, combination treatment with TRAIL and 5-fluorouracil (5-FU) against renal cell carcinoma was also investigated. The NC65 renal cell carcinoma line was used as a target. pCAGGS TRAIL was injected into the NC65 tumors in the right flanks of severe combined immunodeficient mice. Tumors were pulsed with the CUY21 electroporator. Electroporation was done once on day 0 or thrice on days 0, 2, and 4. Apoptosis was determined by terminal deoxyribonucleotide transferase-mediated nick-end labeling assay. When TRAIL gene therapy using in vivo i.t. electroporation was done once only, the growth of NC65 tumors was not inhibited. However, when TRAIL gene therapy was done thrice, growth suppression of the NC65 tumors was observed. Transfection of the TRAIL gene by in vivo electroporation induced apoptosis in NC65 tumors. When NC65 cells were treated with TRAIL gene therapy in combination with 5-FU, stronger growth suppression was obtained. TRAIL gene therapy did not induce liver dysfunction in severe combined immunodeficient mice. This study shows that TRAIL gene therapy induced growth suppression and apoptosis in NC65 tumors without severe side effects, and that combination treatment of NC65 cells with TRAIL gene therapy and 5-FU resulted in higher antitumor activity. These findings suggest that TRAIL gene therapy and/or 5-FU may be effective against renal cell carcinoma without harmful toxic effects.

Animals↗

[Effects of the diversity and relative dimension of the peripheral objects on the meaning of the qualifying word for young children].

Two experiments were conducted to test 100 children (aged five years) on an object named novel word selection task. In Experiment 1, the experimenter labeled a novel word to a target object (an elephant) which was in a cage alone, or which was in a cage with many objects (other animals and instruments) around it. In the former case, the subjects usually qualified the word meaning only when similarly restricted by its peripheral objects (a cage). In the latter case, the subjects were likely to qualify the word meaning with a conceptual level name (an elephant). In Experiment 2, the experimenter labeled a novel word to a target object which was in a small cage, or in a large cage. In the former case, the subjects were likely to qualify the word meaning only when being similarly restricted by its peripheral objects. In the latter case, the subjects were likely to qualify the word meaning with a conceptual level name. These findings suggested that, for young children, objects peripheral to a target object had an effect on the meaning of the qualifying word.

Child, Preschool↗

Secondary acute monocytic leukemia with a translocation t(8;16)(p11;p13): case report and review of the literature.

Acute myeloblastic leukemia cases carrying the translocation t(8;16) (p11;p13) are characterized by the M4 and M5 subtypes, erythrophagocytosis by the blast cells and a poor prognosis, suggesting a new clinical entity. The t(8;16) fuses the MOZ gene which encodes a histone acetyltransferase, located on 8p11 with the CBP gene which also encodes a histone acetyltransferase, located on 16p13, and recent reports suggested that the chimeric transcription MOZ-CBP is essential for leukemogenesis. A 68-year-old woman who had been treated mainly with paclitaxel and carboplatin for preceding ovarian cancer was admitted to our hospital, complaining of right breast mass. She was diagnosed as having breast cancer and acute monocytic leukemia (M5b). Cytogenetic study with spectral karyotyping analysis revealed the development of 47 XX, + 8, t(8;16)(p11;p13). Eleven cases of therapy-related t(8;16) leukemia including the present case have been reported, but prior treatment with paclitaxel and carboplatin-based chemotherapy has never been reported. The relation of histone acetylase and therapy-related leukemia is discussed.

Aged↗

Diffuse large B-cell lymphoma presenting with hypercalcemia and multiple osteolysis.

Osteolysis and hypercalcemia are observed in 5-15%, and 10%, respectively, of malignant lymphoma patients during their clinical course. However, both osteolysis and hypercalcemia are uncommon at onset of the disease. We encountered a 24-year-old male non-Hodgkin's lymphoma patient who had multiple osteolytic lesion from the onset of the disease and repeated episodes of hypercalcemia during the clinical course. The patient died with refractory disease. We studied the expression of chemokines which might affect bone resorption using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Increased expressions of MIP-1alpha, MIP-1beta and RANKL, which are osteoclast-activating factors, were observed in the RNA derived from the patient's lymphoma cells. The secretion of osteoclast-activating factors such as MIP-1alpha by the tumor cells (and/or bone marrow stromal cells) might be involved in the etiology of osteolysis and hypercalcemia in some malignant lymphoma cases.

Acid Phosphatase↗

Analysis of numbers of repeated units in R2 region among varicella-zoster virus strains.

BACKGROUND: A variable region, R2, on the varicella-zoster virus (VZV) genome contains a repeated 42-bp unit. OBJECTIVE: The purpose of this study is the derivation of significance from tandem reiteration structure in the R2 region. METHODS: Fifty-two specimens were collected from 52 patients with herpes zoster in Osaka and Tokyo, Japan. After treatment of the specimens to release viral DNA, the samples were amplified directly by polymerase chain reaction. In addition, 14 samples were collected from 7 of these zoster patients after valaciclovir or aciclovir therapy. RESULTS: Analyses of the 52 specimens revealed that the number of repeats ranged from 4 to 13. Interestingly, the numbers of repeats among various VZV strains showed a normal distribution pattern, so that 6-9 repeats were found to be predominant in both Osaka (85%) and Tokyo (72%). The pre- and post-treatment strains taken from the same individuals showed the same numbers of repeats (7-9 in 6 cases and 11 in one). CONCLUSION: Our results suggest that the 6-9 repetitions of the 42-bp unit, with presumed stability, may offer these virus strains an advantage in virulence to human skin.

Acyclovir↗

Peripheral T-cell lymphoma presenting with rapidly progressing myelofibrosis.

Myelofibrosis following peripheral T-cell lymphoma has rarely been reported. Described here is a case of peripheral T-cell lymphoma with myelofibrosis and elevated transforming growth factor beta (TGF-beta). A 69 years old male was admitted due to anemia and thrombocytopenia. His bone marrow showed fibrosis and was infiltrated with small lymphoid cells and a few residual normal hematopoietic cells. He had presented with hepatosplenomegaly and left inguinal lymph node swelling. Biopsy of the left inguinal lymph node revealed diffuse mature small lymphoid cells with atypical nuclei. Immunophenotyping of the small lymphoid cells were positive for CD3, CD8, TCR alphabeta and HLA-DR and were negative for CD4, CD19, CD20 and CD56. T-cell receptor beta-chain gene was rearranged in bone marrow cells. He was diagnosed as having peripheral T-cell lymphoma complicated with myelofibrosis. Chemotherapy was administrated which improved his pancytopenia and symptoms. Two years later, anemia and thrombocytopenia developed rather quickly, he died because of progression of myelofibrosis with severe pancytopenia.

Aged↗

Increased expression of c-maf in pure red cell aplasia secondary to plasma cell dyscrasia.

Th2 dominancy in the peripheral T helper (Th) cell subsets were reported to be involved in the pathogenesis of pure red cell aplasia (PRCA). We encountered a PRCA case secondary to plasma cell dyscrasia that showed Th2 dominancy at the relapse of PRCA. Increased expression of c-maf, a transcriptional factor which induces Th2 differentiation of naive T-cells, and elevated expression of interleukin (IL)-4 were observed in the RNA derived from patient's bone marrow at relapse of PRCA. Following the administration of methylprednisolone which improved PRCA, normalization of Th1/Th2 ratio and decreased expression of c-maf and IL-4 were observed, which suggests that the upregulation of c-maf might have played a role in the pathogenesis of PRCA secondary to plasma cell dyscrasia.

Aged↗

Aberrant methylation in promoter-associated CpG islands of multiple genes in therapy-related leukemia.

Methylation profile was analyzed in eleven cases of therapy-related leukemia (t-leukemia) for p14, p15, p16, Rb, hMLH1, hMSH2, MGMT, APC, RAR beta, DAPK, RIZ1, FHIT, and SOCS-1 genes by using methylation specific polymerase chain reaction (MSP) analysis. Six (55%) of eleven cases showed methylation of at least one gene. The average time to the development of t-leukemia after the treatment of the primary tumor was significantly shorter in patients with methylation than those without methylation (49.3 months vs. 133.2 months, P=0.044). These results suggest that hypermethylation might be involved in the development of t-leukemia.

Aged↗

Marked thrombocytosis following relapse of acute myeloblastic leukemia associated with development of translocation (2;14) (p13;q32).

Thrombocytosis is a rare finding in acute myeloblastic leukemia (AML). Here, we describe a patient with AML who relapsed with marked thrombocytosis. The patient was initially diagnosed as having AML (M4) with a low platelet count. The patient was started on combination chemotherapy including high-dose etoposide and achieved complete remission. However, the patient relapsed six months later with an extremely high platelet count (72.5 x 10(4)/microl). Cytogenetic analysis at relapse revealed the development of t(2;14)(p13;q32). Despite the repeated combination chemotherapy, the patient died with progressive disease. This case suggests that the additional chromosomal aberration t(2;14)(p13;q32) may be related to abnormal thrombocytosis in AML.

Adult↗

EBV associated hemophagocytic syndrome accompanied by central pontine myelinolysis.

The development of central pontine myelinolysis (CPM) has rarely been reported in association with hemophagocytic syndromes (HPS). Here we report a unique case of Epstein-Barr Virus (EBV)-related HPS which was accompanied with CPM. A 72-year-old man who had no significant medical history was admitted to our hospital due to high fever and progressing dysphasia and dysarthria. Physical examination revealed anisocoria of the right pupil, fixed reaction to light, and paralysis of the left vagus nerves. Magnetic resonance imaging revealed low signal intensity on T1-weighted images and high signal intensity T2-weighted images in the patient's central midpontine lesion. Initial work-up showed anemia and thrombocytopenia with elevated levels of serum ferritin, lactate dehydrogenase, and soluble IL-2 receptor. Bone marrow aspiration revealed hemophagocytosis. The EBV genome was detected in the peripheral blood using the polymerase chain reaction method. He was diagnosed as having EBV-related HPS and CPM. Despite intensive treatment with methylpredonisolone, immunoglobulin, and etoposide, he died due to progressive disease and fungal septicemia. The etiology and relation between CPM and HPS are discussed.

Aged↗

[Reversible cardiomyopathy secondary to interferon-alpha in chronic myelogenous leukemia].

Interferon-alpha (IFN-alpha) has been accepted as an effective agent in the treatment of chronic myelogenous leukemias (CML). Cardiac toxicity of IFN-alpha has rarely been reported in cases of CML. A 62-year-old woman with a two-year history of chronic myelogenous leukemia who had been treated with IFN-alpha (10 million U/3 days/week) given subcutaneously with oral hydroxycarbamide 500 mg, presented with chest pain, dyspnea and subconsciousness. Chest X-ray revealed cardiomegaly and congestion, and ultrasonography showed diffuse hypokinesis of the heart with decreased left ventricular ejection fraction (LVEF) 34%. She was diagnosed cardiomyopathy caused by IFN-alpha administration. She was treated with furosemide, dobutamine hydrochloride, milrinone and carperitide. The administration of IFN-alpha was terminated. LVEF was improved to 50% within one month from the onset of events, and the patient was discharged. We discuss herein the cardiomyopathy caused by IFN-alpha in CML.

Cardiomyopathies↗

[Lupus cystitis in the course of Evans syndrome].

A 50-year-old woman with a 4-year history of Evans syndrome was admitted to our hospital because of progressive nausea, appetite loss, body weight loss, diarrhea and abdominal pain. Abdominal ultrasonography revealed pleural effusion, ascites, bilateral hydronephrosis, dilatation of the bilateral ureter, and irregular wall thickness of the urinary bladder. Immunological studies revealed decreased complement components (C3; 72 mg/dl, C4; 7 mg/dl, CH50; 28.8 mg/dl), a x 80 antinuclear antibody titer (homogeneous pattern), antibody against single-stranded DNA 19 U/ml, anti-SS-A antibody over 500 U/ml and negativity for antibody against double-stranded DNA (anti-dsDNA Ab). Although the patient did not fulfill the criteria for systemic lupus erythematosus (SLE), we diagnosed her as having lupus cystitis. Bolus methylprednisolone (mPSL) therapy (1,000 mg mPSL over 3 days, div) was administered, followed by 60 mg PSL, and this led to immediate improvement of the patient's symptoms and laboratory data. Later, anti-dsDNA Ab became positive, and the patient thereby fulfilled the criteria for SLE. Lupus cystitis following Evans syndrome has rarely been reported. The present such case was treated successfully with bolus mPSL therapy.

Anemia, Hemolytic, Autoimmune↗