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Biomedical subjects

H Tsutani

Publications and source records attributed to H Tsutani.

At least 55 records · Page 3Linked to original sources
PubMed1993

Discordant LFA-1/ICAM-1 expression in a case of secondary plasma cell leukemia associated with subcutaneous plasmacytoma.

We observed a unique case of multiple myeloma that was transformed into plasma cell leukemia presenting with subcutaneous and soft tissue infiltrates. Subcutaneous and minor pelvic soft tissue plasmacytomas and the leukemic transformation were diagnosed in a 72-year-old woman after she had completed 9 months of chemotherapy for IgG kappa multiple myeloma. Immunophenotypic study revealed that leukemic cells in her peripheral blood were positive for ICAM-1 (CD54) but negative for LFA-1 alpha (CD11a) and LFA-1 beta (CD18), whereas infiltrating leukemic cells in the subcutaneous plasmacytoma of the left thigh were positive for LFA-1 alpha and LFA-1 beta but negative for ICAM-1. In addition, intermingling capillary endothelial cells were positive for ICAM-1. Extramedullary soft tissue plasmacytoma is uncommon in association with plasma cell tumors, and the exact mechanism of the development of plasmacytoma is not known. In the present case, however, the discordant expression of LFA-1/ICAM-1 adhesion molecules may have accounted for the distinct patterns of growth and the spread of the subcutaneous plasmacytoma through homing of the LFA-1 alpha+, LFA-1 beta+ leukemic cells to ICAM-1+ endothelial cells.

Aged↗
PubMed1993

Interleukin-2 receptor alpha chain on acute myelocytic leukemia cells is involved in cell-to-cell interactions.

Leukemic cells from 21 to 197 adult patients with de novo acute myelocytic leukemia (AML) were positive for IL-2R alpha chain (IL-2R alpha), whereas IL-2R beta chain (IL-2R beta), which is responsible for IL-2 signal transduction, was not found on leukemic cells from any of these cases tested. The expression of IL-2R alpha was closely associated with that of adhesion molecules CD4, CD11b and CD22, and endopeptidase CD10. None of the IL-2R alpha (+) AML cells responded to recombinant human IL-2. These data suggest that IL-2R alpha on AML cells may not be involved in cellular proliferation as one of growth factor receptors but may have a role in the control of cell-to-cell interactions.

Adult↗
PubMed1993

Sequential promotion of normal and leukemic hemopoiesis by recombinant human granulocyte colony-stimulating factor during the course of myelodysplastic syndrome.

A 48-year-old man developed refractory anemia with excess of blasts in transformation. Complete response was achieved by low-dose ara-C therapy, but he relapsed 15 months later, with pancytopenia and 13.0% myeloblasts in normocellular marrow. He was treated unsuccessfully with prednisolone, metenolone, and 1-alpha-hydroxyvitamin D3 for 8 weeks. He then developed life-threatening pneumonia and was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF Filgrastim; 125 micrograms/day s.c.). The pneumonia resolved and, interestingly, he achieved a partial response, with normal blood cell counts and only a few dysmyelopoietic cells in the marrow. However, thrombocytopenia progressed when rhG-CSF administration was tapered. When the dose was increased again, leukemic blasts were found to proliferate. When rhG-CSF was discontinued, blasts rapidly decreased in the peripheral blood. Chromosomal analysis revealed a complex abnormality during the first relapse, a normal 46,XY karyotype during the partial response, and recurrence of the same complex abnormality during leukemic transformation. The stimulation index of marrow mononuclear cells cultured with rhG-CSF increased with disease progression. These findings suggest that rhG-CSF initially stimulated the selective proliferation of normal hemopoietic cells, but the evolution or selection of a leukemic clone responsive to rhG-CSF appears to have occurred subsequently.

Follow-Up Studies↗
PubMed1993

A granulocytic population with rearranged immunogenotype in chronic myelocytic leukemia blast crisis and Philadelphia-chromosome-positive acute leukemia with cross-lineage nature.

Two patients with chronic myelocytic leukemia (CML) mixed crisis and one with Philadelphia-chromosome-positive (Ph1 +) acute lymphoblastic leukemia (ALL) with cross-lineage nature had a considerable number of granulocytes with monoclonally rearranged immunogenotype. The gene configurations of immunoglobulin heavy chain (IgH), T-cell receptor beta chain (TCR beta), and gamma chain (TCR gamma) in the granulocytic cells were identical to those in the blasts, indicating that both the blasts and the granulocytes were derived from common leukemic progenitors with the IgH gene rearrangements. In a colony assay of cells from in the Ph1 + ALL patient, the leukemic cells showed the potential to differentiate into granulocytes in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF). Interleukin 7 (IL-7) exerted synergistic effects on colony and cluster formation in cultures with these cytokines. Further, IL-3, GM-CSF, and G-CSF receptor gene expression was found in the leukemic cells. Our findings indicate that the Ph1 + common progenitors in these three patients preserved the potential for granulocytic differentiation even after the occurrence of the Ig (and TCR) gene rearrangements as the first genomic event in lymphocyte differentiation. The phenomenon of cross-lineage in leukemic cells, at least in Ph1 + leukemia, can be considered to demonstrate the potential of leukemic progenitors to differentiate in multiple directions.

Base Sequence↗
PubMed1993

[Treatment of myelodysplastic syndromes with cytokines].

To evaluate the effects of colony-stimulating factors (CSFs) on pathological cells from myelodysplastic syndromes (MDS), CD34-positive cell fractions (mainly blast cells) from nineteen MDS patients and four normal volunteers were successfully enriched by the use of immunomagnetic beads, and their responsiveness to CSFs was examined in short-term liquid suspension cultures. Considerable parts of blast cells from MDS patients remained immature as compared with the favorable maturation of normal blast cells, especially in high-risk MDS group that included two prominent cases with a remarkable blast cell growth without maturation induction by CSFs. Short-term clinical administrations of G-CSF often brought about hematological improvements on MDS patients. Other cytokines are also reported to be of use on some patients. However, a few cases progressed to overt leukemia in relation to G-CSF treatment. Much care should be taken with in vivo application of CSFs to high-risk MDS patients, although there may be no effective clue to foresee the risk of leukemic transformation yet.

Adult↗
PubMed1992

Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells.

The expression of interleukin-2 receptors (IL-2R) was examined in 328 adult patients with non-T-cell (non-T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti-Tac for IL-2R alpha chain (IL-2R alpha) and Mik beta 1 for IL-2R beta chain (IL-2R beta). Leukaemic cells in the following cases were positive for anti-Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML-BC, 4/28 CD19(+)CD10(-) acute lymphoblastic leukaemia (ALL), and 20/64 common ALL (c-ALL). IL-2R beta was not detected on leukaemic cells of any case examined. Eleven of IL-2R alpha(+) AML were derived from myelodysplastic syndrome. None of the IL-2R alpha positive leukaemic cells responded to exogenous recombinant human IL-2 (rhIL-2) in culture. In addition, IL-2R alpha expression on non-T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL-2R alpha was demonstrated in the IL-2R alpha(+) patients examined. Clinically, the IL-2R alpha(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL-2R alpha(-) patients. Our results clearly indicate the diagnostic importance of IL-2R alpha expression in non-T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.

Acute Disease↗
PubMed1992

Prophylactic use of ofloxacin in granulocytopenic patients with hematological malignancies during post-remission chemotherapy.

The prophylactic efficacy of ofloxacin (OFLX) therapy was evaluated in 51 granulocytopenic episodes in 22 patients with hematological malignancies during post-remission chemotherapy in a prospective, randomized, controlled trial. Oral administration of OFLX plus amphotericin-B (AMPH) and polymyxin-B (PL) reduced episodes of fever and infection more than did the control regimen with PL and AMPH alone (p less than 0.01), and the reduction in the incidence of infection was evident even in patients showing severe granulocytopenia (p less than 0.01). Furthermore, the first fever after the onset of granulocytopenia in the OFLX regimen developed later than that in the control regimen (p less than 0.05). Clinically, the prophylactic efficacy was 92% for the OFLX regimen and 40% for the control regimen (p less than 0.01). These findings suggest that OFLX is a promising prophylactic agent following post-remission chemotherapy. Patient hemomyelogram findings similar to those of patients with other malignancies may imply that OFLX is widely effective in granulocytopenic patients taking aggressive chemotherapy.

Adolescent↗
PubMed1991

Pharmacological studies of retinol palmitate and its clinical effect in patients with acute non-lymphocytic leukemia.

The pharmacokinetics of retinol palmitate were studied, and a therapeutic trial was performed in patients with ANLL. In the pharmacokinetics study, retinol was the only metabolite that was detected in plasma, and the peak concentration was 332 micrograms/dl (about 1.2 x 10(-5) M) 2.1 h after administration of retinol palmitate. Five patients with ANLL (4 with ANLL-M3 and one with ANLL-M2) were treated with retinol palmitate. In all patients with ANLL-M3, bone marrow suspension culture studies revealed that retinol induced both morphological and functional differentiation of immature leukemic cells. During the course of the treatment with retinol palmitate, morphological differentiation of bone marrow immature leukemic cells was observed in all patients with ANLL-M3 within 3-4 days after initiation of the therapy. In three of the four patients who underwent conventional chemotherapy, the sequential treatment with retinol palmitate resulted in a complete remission: controlling residual bone marrow leukemic cells. None of the patients showed any signs of aggravation of DIC in the coagulation parameters. These findings suggest the possibility that retinol palmitate functions as salvage therapy by inducing maturation and slowing proliferation, there by clearing out the residual leukemic cells following conventional chemotherapy.

Adult↗
PubMed1991

[Fulminant hepatitis cured by plasma exchange in a patient with acute leukemia--a case report].

A 16-year-old male with acute myelogenous leukemia (M1) presented with fulminant hepatitis (massive hepatic necrosis). He achieved a complete remission with the administration of AdVP (doxorubicin, vincristine and prednisolone), and thereafter received consolidation or intensification therapy 5 times in combination with AdVP plus enocitabine. A bone marrow examination carried out before the 6th round of chemotherapy revealed a slight increase of myeloblast (7%). L-AdVP (including l-asparaginase in addition to AdVP) was administered with a good result. However, 13 days after the end of the therapy he complained of acute abdominal pain, headache and fever. The following day, his consciousness level became lower and severe jaundice appeared. The serum transaminase level highly elevated with PT and aPTT severely elongated. He was diagnosed as having fulminant hepatitis. Elevation of the titer of IgM-HBc suggested that the fulminant hepatitis was attributed to HBV, which was probably transmitted by blood transfusion done in the first induction therapy and stayed latent during immunosuppressive chemotherapy. After receiving 10 sessions of plasma exchange (3.2 l/day), he recovered, free from any major complications except posttransfusion hepatitis. In his serum taken at 1 month after the recovery of posttransfusion hepatitis, HCV (Chiron) antibody was detected. There have been few reports concerning fulminant hepatitis associated with acute leukemia. In this case, plasma exchange was very effective in treating fulminant hepatitis.

Acute Disease↗
PubMed1990

[Activities of enzymes converting 5-fluorouracil to 5-fluorouridine-5' monophosphate and 5-fluorodeoxyuridine-5' monophosphate in subcultured cell lines and solid tumor tissues].

The activities of five enzymes, orotate phosphoribosyltransferase (OPRTase), uridine kinase (UR kinase), thymidine kinase (TdR kinase), uridine phosphorylase (UR Prylase) and thymidine phosphorylase (TdR Prylase), were examined in subcultured human acute leukemia cell lines (HL-60, CCRF-CEM), subcultured human solid tumor cell lines (Colo-205, HeLa-S3) and human cancerous tissues with a view to compare the activation of 5-fluorouracil in them. There was no significant difference in the activity of any enzyme between HL-60 and CCRF-CEM, Colo-205 and HeLa-S3, and human lung cancerous tissue and human colon cancerous tissue. Compared between the acute leukemia cell lines and the solid tumor cell lines, the UR kinase activity was high in both cell lines. The OPRTase and UR Prylase activities were low in the solid tumor cell lines. In the cancerous tissues, both the UR kinase and TdR kinase activities were low, but the UR Prylase and TdR Prylase activities were markedly high. The results suggest that the intracellular activation of 5-fluorouracil varies with different human cancerous cells. When the anti-cancer activity of 5-fluorouracil is tested in vitro, the difference of fluoropyrimidine metabolism in subcultured cell lines from that in the cancerous tissue should be taken in account.

Fluorouracil↗
PubMed1990

[Clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in a patient with acute non-lymphocytic leukemia with two CNS recurrences].

A case of two repeated CNS recurrences of acute non-lymphocytic leukemia (M2) was treated with intermediate dose Ara-C therapy and achieved 2 complete remissions. The clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in this patient were discussed. A 55-year-old male with acute non-lymphocytic leukemia (M2) achieved complete remission by combination chemotherapy of Behenoyl-ara-C, Daunorubicin, 6-Mercaptopurine and Prednisolone in July, 1985. He subsequently received consolidation and intensification therapy with periodical intrathecal injection of Methotrexate (MTX), but 13 months later he developed his first CNS recurrence which was resistant to the intrathecal administration of Ara-C and MTX. As he also relapsed systemically, Ara-C was administered in intermediate dose (1 g/m2 every 12 hrs for 5 days) and he achieved complete remission both in the CNS and systemic manifestations. Six months later he was diagnosed as having a second CNS recurrence and another systemic relapse. Intermediate dose Ara-C was administered again, and he achieved complete remission in the CNS and partial remission in systemic manifestations. Pharmacokinetic study revealed high peaks of Ara-C concentration in plasma (6.2 microM immediately after the end of the infusion) and high degree of its penetration into the CNS (5.6 microM at 3 hr after the end of the infusion) suggesting the effective and perhaps a uniform level of Ara-C is achieved throughout the CNS by this therapy. In 3 other patients without CNS involvement 0.88 +/- 0.44 microM of Ara-C, which is enough concentrations for its cytostatic effect, was detected at 3 hr after the end of infusion, suggesting the efficacy of the therapy for CNS prophylaxis. In this case the relapse occurred after repeated administration of antileukemic drugs, including Behenoyl-ara-C, an analog of Ara-C, and was resistant to the intrathecal administration of Ara-C. These findings suggest that intermediate dose Ara-C therapy was effective to overcome a resistance to antileukemic drugs, including Ara-C, and also, in some cases, more effective than intrathecal injection of antileukemic drugs for the treatment of CNS leukemia.

Cytarabine↗
PubMed1990

Reduction of leukemia cell growth in a patient with acute promyelocytic leukemia treated by retinol palmitate.

A 67-year-old woman with acute promyelocytic leukemia (APL) showed a marked decrease in leukemic promyelocytes with concomitant maturation of leukemic cells during treatment with retinol palmitate. A culture study in vitro revealed that retinol, which is the main metabolite of retinol palmitate detected in plasma, induced morphological and functional maturation of leukemic promyelocytes. These findings may indicate that retinol palmitate induces cell differentiation and slows proliferation of leukemic cells in vivo, and that the reduction in cell growth is the key phenomenon in the clearing of leukemic cells, rather than the maturation phenomenon itself.

Aged↗
PubMed1990

[Blastic crisis of primary myelofibrosis associated with multiple myeloblastomas ].

The patient is a 71-year-old female who underwent splenectomy due to splenomegaly 32 months after diagnosed as having primary myelofibrosis. On examination she was found to have massive skin nodules, lymph nodes swelling and an enlarged liver with an abnormal hematologic profile as follows: RBC count 3.68 x 10(6)/microliters; WBC count 151 x 10(3)/microliters with 11% blasts; and platelet count 42 x 10(3)/microliters. The bone marrow aspirate showed a hypocellular marrow with 19.2% blasts. Histological examination of the skin nodules revealed that they were myeloblastomas, thus suggesting leukemic transformation of primary myelofibrosis. Her WBC count dropped to about 20 x 10(3)/microliters through treatment with vindesine, cyclophosphamide, 6-mercaptopurine and prednisolone, but it did not drop further. Treatment with dexamethasone remarkably regressed the myeloblastomas, but she died of heart failure 4 months after diagnosis of leukemic transformation of primary myelofibrosis. The autopsy findings showed the formation of numbers of myeloblastomas in both the systemic fatty tissue and dura mater as well as extramedullary hematopoiesis in liver and lymph nodes. A rapid development of splenomegaly in a patient with primary myelofibrosis seems to be associated with leukemic transformation.

Aged↗
PubMed1990

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) accompanied with severe thrombocytopenia and interstitial pneumonitis].

A case of generalized lymphadenopathy with severe thrombocytopenia and marked polyclonal hypergammaglobulinemia is reported. A 51-year-old man was admitted to the hospital because of nasal bleeding and generalized lymphadenopathy. Laboratory examination revealed a platelet count of 6,000/microliters, a total protein level of 11.6 g/dl, and a gammaglobulin level of 8.7 g/dl including 6,726 mg/dl IgG, 1,119 mg/dl IgA, 265 mg/dl IgM, 265 mg/dl IgD and 226 IU/ml IgE. Neither definite evidence suggesting viral infection nor an autoimmune disease was found except slightly elevated titers of anti-microsome and anti-thyroglobulin antibodies. The chest X-ray revealed diffuse reticular shadowing suggesting interstitial pneumonitis. The cervical lymph node biopsy revealed massive infiltration by IgG-, IgA-, and IgM-positive plasmocytoid cells in the paracortical T cell areas, but no destruction of normal architecture of lymph node. The treatment with prednisolone resulted in a decrease in the severity of the lymphadenopathy, thrombocytopenia and polyclonal hypergammopathy. He is still well; however, interstitial pneumonitis, mild thrombocytopenia, and polyclonal hypergammopathy have persisted for 4 years. The histological findings in this case are similar to those in the case of Castleman lymphoma of a plasma cell type. Thus, considering the clinical data and clinical course, the diagnosis in this case is likely to be idiopathic plasmacytic lymphadenopathy with polyclonal hyperglobulinemia as a subtype of the plasma cell type of Castleman lymphoma. However, the accompanying interstitial pneumonitis and the severe thrombocytopenia, which was caused by excessive platelet destruction or by the suppression of megakaryocytes by proliferated plasma cells, are unique and are not found in any of the previously reported cases.

Humans↗