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Biomedical subjects

K Uozumi

Publications and source records attributed to K Uozumi.

At least 19 recordsLinked to original sources

Liver CT image processing: a short introduction of the technical elements.

In this paper, we describe the technical aspects of image analysis for liver diagnosis and treatment, including the state-of-the-art of liver image analysis and its applications. After discussion on modalities for liver image analysis, various technical elements for liver image analysis such as registration, segmentation, modeling, and computer-assisted detection are covered with examples performed with clinical data sets. Perspective in the imaging technologies is also reviewed and discussed.

Humans↗

Expression of functional lung resistance--related protein predicts poor outcome in adult T-cell leukemia.

Chemotherapy of patients with adult T-cell leukemia (ATL) has been unsuccessful. The poor outcome is thought to be caused mainly by the drug resistance of ATL cells. Lung resistance-related protein (LRP) is a novel protein associated with drug resistance. The expression of LRP messenger RNA (mRNA) was evaluated by slot blot analysis in 55 patients with ATL. Of these patients, 36 had acute, 12 chronic, and 7 lymphoma-type ATL. The expression levels of LRP mRNA were significantly higher in chronic ATL than in lymphoma-type ATL (P =.007). The expression of LRP mRNA was higher in patients with white blood cell counts above 30,000/microL (P =.038) or with abnormal lymphocyte counts above 10,000/microL (P =.007) than in the remaining patients. The enhanced efflux of [(14)C]doxorubicin from nuclei isolated from ATL cells that expressed high levels of LRP was inhibited by a polyclonal antibody against LRP, and the accumulation of doxorubicin in the isolated nuclei was increased by the anti-LRP antibody. In acute and lymphoma-type ATL patients, high expression of LRP mRNA at diagnosis correlated with shorter survival, and a Cox proportional hazards model showed that LRP expression is an independent prognostic factor. These findings suggest that functionally active LRP is expressed in some ATL cells and that it is involved in drug resistance and poor prognosis in ATL. (Blood. 2001;98:1160-1165)

Active Transport, Cell Nucleus↗

Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation.

Adult T cell leukemia/lymphoma (ATL) is a poor prognosis T cell malignancy. In order to improve the outcome, we employed allogeneic stem cell transplantation (allo-SCT) for ATL in 10 patients, nine of whom were from HLA-identical siblings and one from an unrelated donor. Conditioning regimens varied among the patients except that all received total body irradiation. The patients tolerated the regimens well with mild, if any toxicity, and engraftment occurred in all cases. Median leukemia-free survival after allo-SCT was 17.5+ months (range 3.7-34.4+). Six of the 10 patients developed acute GVHD (one case each with grade I, III or IV, and three cases with grade II) and three patients developed extensive chronic GVHD. Four patients died after allo-SCT during the study period from either acute GVHD (grade IV), pneumonitis, gastrointestinal bleeding or renal insufficiency. Two of the 10 cases with no symptoms of GVHD relapsed with clinical ATL. These results strongly suggest that allo-SCT may improve the survival in ATL if a controlled degree of GVHD develops.

Adult↗

Prognostic significance of multidrug resistance protein in adult T-cell leukemia.

The response of adult T-cell leukemia (ATL) to chemotherapy is poor, and a major obstacle to successful treatment is intrinsic or acquired drug resistance. To determine the clinical significance of multidrug resistance protein (MRP) 1 in ATL, we studied MRP1 expression and its association with clinical outcome. The expression of MRP1 mRNA in leukemia cells from 48 ATL patients was studied by slot blot analysis. The expression level of MRP1 mRNA in chronic-type ATL was significantly higher than that in lymphoma-type ATL (P = 0.033). There was no correlation between MRP1 expression and age, gender, WBC count, LDH, hypercalcemia, blood urea nitrogen, or performance status. However, the expression of MRP1 mRNA correlated only with peripheral blood abnormal lymphocyte counts (P = 0.008). The transporting activity of MRP1 was assessed using membrane vesicles. Membrane vesicles prepared from ATL cells with high expression of MRP1 mRNA showed a higher ATP-dependent leukotriene C(4) uptake than did those with low expression of MRP1 mRNA. This uptake was almost completely inhibited by LTD(4) antagonists ONO-1078 and MK571. In acute- and lymphoma-type ATL, high expression of MRP1 mRNA at diagnosis correlated with shorter survival, and Cox regression analysis revealed that MRP1 expression was an independent prognostic factor. These findings suggest that functionally active MRP1 is expressed in some ATL cells and that it is involved in drug resistance and has a possible causal relationship with poor prognosis in ATL. Multidrug resistance-reversing agents, such as ONO-1078 and MK571, that directly interact and inhibit the transporting activity of MRP1 may be useful for treating ATL patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Establishment and characterization of a new human megakaryoblastic cell line (SET-2) that spontaneously matures to megakaryocytes and produces platelet-like particles.

A new factor-independent megakaryoblastic cell line, designated SET-2, was established from the peripheral blood of a patient with leukemic transformation of essential thrombocythemia (ET). SET-2 expressed CD 4, 7, 13, 33, 34, 36, 38, 41, 61, 71, 117, 126, 130 and c-mpl. In addition, it spontaneously produced numerous platelet-like particles in liquid culture. These particles were shown to be the same size as normal platelets, and to express CD 36, 38, 41, 61 and 71. Proliferation of SET-2 was not influenced by thrombopoietin (TPO) and other hemopoietic cytokines. SET-2 was found to express the platelet-specific proteins such as platelet factor 4 and beta-thromboglobulin. The levels of expression were not altered by TPO. SET-2 also secreted interleukin-6 into the supernatants, as well as normal megakaryocytes. These results suggest that SET-2 spontaneously matures to megakaryocytes and produces platelet-like particles. These findings indicate that SET-2 may be useful for investigating the proliferation and differentiation mechanisms of leukemia cells and the role of c-mpl on megakaryoblasts, megakaryocytes, and platelets in ET. Leukemia (2000) 14, 142-152.

Aged↗

Arsenic trioxide and the growth of human T-cell leukemia virus type I infected T-cell lines.

A novel therapeutic potential for acute promyelocytic leukemia using arsenic trioxide (As(2) O(3) ) has been reported. Recent in vitro studies demonstrated that As(2) O(3) effectively inhibits the growth of some cell lines derived from patients with malignant lymphoma, chronic lymphocytic leukemia and multiple myeloma. Adult T-cell leukemia (ATL) is an aggressive neoplasm of mature T-cell origin caused by human T-cell leukemia virus type-I (HTLV-I) the prognosis of which still remains very poor. A possible role of As(2) O(3) for the treatment of ATL is demonstrated from evidence that As(2) O(3) significantly inhibits the growth of HTLV-I infected T-cell lines and induces apoptosis in fresh ATL cells at clinically achievable concentration of the agent. The growth inhibition of As(2) O(3) treated HTLV-I infected T-cell lines was induced by both apoptosis and G(1) phase accumulation. Cleaved bcl-2 protein and an enhanced expression of bak protein in the cells were coincidentally observed during As(2) O(3) treatment. A broad spectrum caspase inhibitor, z-Val-Ala-DL-Asp-fluoromethylketone inhibited the apoptosis induced by As(2) O(3). Increased expression of p53, Cip1/p21 and Kip1/p27, and dephosphorylation of retinoblastoma protein (pRb) were detected in the As(2) O(3) treated cells. In conclusion, As(2) O(3) might become a new therapeutic tool in the treatment of ATL as As(2) O(3) induces apoptosis by destruction of the bcl-2 protein and enhancement of the bak protein production proceeding to activate caspases, and also induces G(1) phase accumulation by enhancement of p53, Cip1/p21, Kip1/p27 and dephosphorylation of pRb to HTLV-I infected T-cell lines.

Amino Acid Chloromethyl Ketones↗

Transient appearance of CD3+CD8+ T lymphocytes with monoclonal gene rearrangement of T-cell receptor beta locus.

A benign, transient proliferation of atypical lymphocytes and a monoclonal rearrangement of the T-cell receptor beta (TRB) locus was found in a 60-year-old woman who presented with low-grade fever, anorexia and fatigue. A marked and transient atypical lymphocytosis (white blood cell count 90.5 x 10(9)/l) with CD8 surface antigen improved without specific treatment. Although tests for IgM antibodies to hepatitis A, varicella zoster, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all negative, a monoclonal gene rearrangement of TRB locus was observed in the DNA of the proliferated atypical lymphocytes by Southern blotting. The clonal rearrangement and the atypical lymphocytes disappeared after 14 d, and the patient has remained well for 7 years. These results suggest that monoclonal proliferation of CD8 lymphocytes can occur based on a non-neoplastic aetiology.

Blotting, Southern↗

Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids.

Adult T-cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T-cell leukaemia virus type I (HTLV-I) infected T-cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV-I-infected T-cell lines was significantly reduced within 72 h by 1.0 micromol/l As2O3. Growth of two out of four HTLV-I-infected T-cell lines was also inhibited by 1.0 micromol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by AS2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 micromol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.

Antineoplastic Agents↗

Granulocyte colony-stimulating factor in the combination chemotherapy for adult T-cell leukemia (ATL).

We evaluated the effect of granulocyte colony-stimulating factor (G-CSF) on the median survival of 17 patients with Adult T-cell leukemia (ATL). Standard-dose combination chemotherapy using the response-oriented cyclic multidrug (RCM) protocol with G-CSF (lenograstim 2 microg/kg/day or filgrastim 50 microg/m2/day) was administered between October 1990 and December 1994. Complete responses (CR) were achieved in 11 (64.7%) patients, and partial responses (PR) in 4 (23.5%) patients. The median duration of survival was 7.4 months, compared with 6.0 months in ATL patients treated with the RCM protocol alone (historical controls) (n.s.). Infectious complications were the cause of death in 4 (26.7%) of the 15 patients who died. The median duration of neutropenia (absolute neutrophil count < 1.0 x 10(9)/L) was 6 days. G-CSF, in the doses and schedules used here, may have shortened the duration of neutropenia and reduced the incidence of fatal infectious complications. However, concomitant use of G-CSF did not prolong the median duration of survival in patients with ATL treated according to the RCM protocol.

Adjuvants, Immunologic↗

Treatment for adult T-cell leukemia.

The purpose of this study was to clarify the clinical efficacy of multidrug chemotherapy for aggressive adult T-cell leukemia (ATL). We report the therapeutic results of treatment of patients with aggressive ATL undertaken between 1986 and 1995. A total of 120 newly diagnosed patients with a performance status of 0-3 and aged < 70 years at diagnosis were entered into the study. Clinical features, including clinical subtypes, serum levels of lactate dehydrogenase and blood urea nitrogen, the response to chemotherapy, and doses of individual chemotherapeutic agents, were evaluated. Of the 120 patients enrolled, 97 had acute-type and 23 lymphoma-type ATL. The complete response rate and median survival of these patients were 25.3% and 9 months, respectively. The 2- and 5-year survival rates were 18.4% and 8%, respectively, and five patients have been alive for > 5 years and are disease-free. These long-term survivors had good prognostic factors at diagnosis. There was no correlation between the doses of the various chemotherapeutic agents and the survival duration. These results indicate that ordinary combined chemotherapy has limited ability to improve the prognosis of aggressive ATL. Our previous study indicated that expression of P-glycoprotein in ATL cells might be involved in resistance to chemotherapeutic agents, particularly doxorubicin, vincristine, and etoposide. Therefore, new therapeutic strategies will be necessary to improve the prognosis of ATL patients.

Adult↗

Identification of interleukin-6 producing fibroblastoid cells in cerebrospinal fluid from patients with leukemic meningitis.

Cytokine producing native cells in cerebrospinal fluid (CSF) have not been identified. So, we investigated the cytokine producing ability of floating cells in CSF from patients with leukemic meningitis. Morphologic study revealed that established cell lines were polygonal or elongated in shape and had an abundant and irregular branched cytoplasm. Immunocytochemical analysis demonstrated positive reactivity with monoclonal anti-fibroblast antibody only. Interleukin-6 (IL-6) was constitutively produced in vitro by these cell lines; both interleukin-1 and lipopolysaccharides significantly increased its synthesis. These findings imply that these fibroblastoid cells are floating in CSF of patients with leukemic meningitis and produce IL-6 in response to various inflammatory stimulations in vivo.

Adult↗

An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support.

SUMMARY: An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.

Adult↗