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Biomedical subjects

C Shimazaki

Publications and source records attributed to C Shimazaki.

At least 109 records · Page 6Linked to original sources

Kinetics of serum cytokines in adults undergoing peripheral blood progenitor cell transplantation.

We investigated the serum cytokine levels (G-CSF, GM-CSF, IL-1 beta, IL-3 and IL-6) using an ELISA in 14 patients with haematological malignancies undergoing peripheral blood progenitor cell transplantation (PBPCT). Serum G-CSF levels in all patients rose immediately after PBPCT, then gradually decreased as the neutrophil counts began to rise. No detectable serum levels of GM-CSF or IL-1 beta were observed, but serum levels of IL-3 rose transiently immediately following PBPCT. Serum levels of IL-6 rose transiently during a fever in four patients. These observations suggest that G-CSF and IL-3 may contribute to the early haemopoietic reconstitution in PBPCT.

Adolescent↗

Effect of granulocyte colony-stimulating factor on hematopoietic recovery after peripheral blood progenitor cell transplantation.

To examine the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery after high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT), 20 patients with hematologic malignancies were divided into two groups. One group was given G-CSF at a daily dose of 50 micrograms/m2 subcutaneously, the other received no G-CSF. Neutrophil recovery was accelerated in the G-CSF treated patients and exceeded 0.5 x 10(9)/l at a median of 10 days post-PBPCT compared with 14 days in the control group (p < 0.01). This reduction led to a decrease in antibiotic use and a trend toward fewer febrile days in the G-CSF treated group.

Adolescent↗

Phenotypic differences of CD34-positive stem cells harvested from peripheral blood and bone marrow obtained before and after peripheral blood stem cell collection.

Using two-color flow cytometry, we analyzed the subpopulations of CD34+ stem and progenitor cells in the blood and bone marrow from 10 patients with hematological malignancies. Peripheral blood mononuclear cells (PBMNC) harvested after chemotherapy (high-dose Ara C and VP-16) and rhG-CSF, and BM mononuclear cells, which were obtained before chemotherapy (BMMNCbefore) and after the stem cell collection (BMMNCafter) were isolated by Ficoll-Hypaque centrifugation. The purified cells were stained with FITC-conjugated anti-CD34 antibody and one of the following PE-conjugated antibodies: anti-CD7, CD10, CD11b, CD11c, CD13, CD19, CD33, CD38, CD45RO, CD56, and HLA-DR. CD34+ PBMNC harvested and the CD34+ BMMNCafter expressed CD13 and CD33 more frequently than CD34+ BMMNCbefore but expressed CD10 and CD19 less frequently than CD34+ BMMNCbefore. These data suggested that harvested PBMNC contain more myeloid lineage committed progenitors than BMMNCbefore, which might contribute to the rapid recovery of neutrophils after peripheral blood stem cell transplantation. No significant phenotypic differences of CD34+ cells between harvested PBMNC and BMMNCafter were observed except for the expression of CD11c. CD34+ PBMNC harvested coexpressed CD11c more frequently than both CD34+ BMMNCbefore and CD34+ BMMNCafter, which expression might be associated with commitment to the monocyte lineage.

Adolescent↗

[Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth].

A 75-year-old female was diagnosed as having multiple myeloma (IgG.lambda type. Stage IIA) with plasmacytoma of the head and back in October, 1989. She obtained partial remission by MCNU and MP therapy, but relapsed with massive ascites in January, 1991. VAD therapy was not effective and she died of multiple organ failure on February 23. Her ascites contained a large number of myeloma cells, and the phenotypic analysis and the response to interleukin-6 (IL-6) of these myeloma cells were examined. The myeloma cells were positive for CD33, CD45, CD45RA, CD63, CD71, plasma cell associated antigens such as CD38, PCA-1, BL3, and various kinds of adhesion molecules: CD11a/CD18 (LFA-1), CD29 (VLA-beta 1), CD44 (H-CAM), CD49d (VLA-4), CD54 (ICAM-1), CD56 (N-CAM), CD58 (LFA-3). IL-6 level in the ascites was increased at 91.0pg/ml. The myeloma cells showed an IL-6 dependent growth, which was inhibited by anti-IL-6 antibody (Ab) and anti-IL-6 receptor Ab in vitro. Myeloma cells appearing in ascites have rarely been reported. Our case suggested that IL-6 was a potent growth factor of myeloma cells through an autocrine mechanism in the ascites, and resulted in an aggressive myeloma.

Aged↗

Reconstitution of lymphocyte subsets after peripheral blood stem cell transplantation: two-color flow cytometric analysis.

The reconstitution of lymphocyte subsets after high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) was studied using two-color flow cytometry in 14 patients with acute leukemia (four AML and two ALL) and malignant lymphoma (six NHL and two HD). The CD3+HLA-DR+ lymphocytes (activated T cells) and CD8+ lymphocytes increased markedly by 4 weeks after PBSCT. Most of the increased CD8+ lymphocytes were CD11b-, S6F1+ cells and CD8+CD11b+ cells remained low throughout the follow-up period. The CD4+ lymphocytes remained below the normal range up to 34 weeks after PBSCT. The ratio of CD4+ to CD8+ lymphocytes (CD4/CD8 ratio) transiently increased and then decreased below 1.0 at 2 weeks after PBSCT. The CD19+ lymphocytes and the CD3-CD16+CD56+ lymphocytes returned to normal levels in the early period. The CD4+CD45RA+ lymphocytes (suppressor-inducer) decreased to below the normal range, while the CD4+CD45RO+ lymphocytes (helper-inducer) increased more rapidly than the CD4+CD45RA+ lymphocytes. This study shows that an immunosuppressed state exists after PBSCT as is seen after bone marrow transplantation (BMT) and that B cell reconstitution is more rapid in PBSCT than in BMT.

Acute Disease↗

Acute myelomonocytic leukemia after treatment with chronic oral etoposide: are MLL and LTG9 genes targets for etoposide?

A patient with secondary acute myelomonocytic leukemia after treatment with chronic oral etoposide (VP-16) for lung cancer is reported. The leukemic cells showed a t(9;11)(p22;q23) translocation. Southern blot analysis revealed the rearrangement of the MLL (ALL-1/HRX) gene at 11q23. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a chimeric mRNA between the MLL gene at 11q23 and LTG9 (MLLT3/AF-9) gene at 9p22. The patient was successfully treated with a VP-16 based regimen. This case is instructive in the understanding of the leukemogenesis of VP-16-related leukemias.

Administration, Oral↗

[Neoplastic angioendotheliosis presenting Tolosa-Hunt syndrome, intraspinal invasion and intraorbital tumor].

A 76-year-old woman with painful erythema on legs and right oculomotor disturbance was diagnosed as neoplastic angioendotheliosis (NAE, B cell type) by skin biopsy. Remission was obtained by 2 courses of VEPA regimen. But 3 months later, she relapsed with right oculomotor, optic, trochlear and trigeminal nerve disturbance which suggested that she had Tolosa-Hunt syndrome. Cerebrospinal fluid (CSF) revealed infiltration of lymphoma cells. She developed intraorbital tumor and died of respiratory failure due to tumor emboli. Autopsy revealed infiltration of tumor cells in the small vessels of systemic organs. This rare case presented intracerebrospinal and intraorbital tumor growth in addition to intravascular infiltration of tumor cells.

Aged↗

[Successful treatment of acute myelogenous leukemia in an elderly patient with cytarabine ocfosfate].

A 77-year-old female with left hemiplegia caused by cerebral infarction and with mild senile dementia was admitted for further examination of hematological abnormalities. She was diagnosed as acute myelogenous leukemia (AML-M5a) according to French-American-British classification. Since intensive combination chemotherapy seemed difficult, she was treated with oral administration of cytarabine ocfosfate (200 mg/day, for 14 days), a cytidine deaminase-resistant derivative of Ara-C, resulting in complete remission. Major side effects were nausea, vomiting and appetite loss, but their incidences were reduced tolerably when cytarabine ocfosfate was given just before sleeping. Cytarabine ocfosfate might be useful to treat AML in elderly patients having certain complications such as cerebrovascular disease.

Administration, Oral↗

[Translocation t(11;14) (q13;q32) in six patients with lymphoid malignancies of mature B-cell phenotype].

We described six patients with t(11;14)(q13;q32) in lymphoid malignancies. Based on the histologic or morphologic findings of these patients, malignant lymphoma diffuse large cell (ML-DL) was diagnosed in two patients, small lymphocytic (SL) in one, mantle zone lymphoma (MZL) in one, prolymphocytic leukemia (PLL) in one, and chronic lymphocytic leukemia with > 10% prolymphocytes (CLL/PL) in one. Three cases showed involvement of the gastro-intestinal tract, and four were leukemic. Five cases were dead 12 to 25 months after the time of chromosomal analysis. Immunological studies revealed that all the patients were positive for CD5, CD20, HLA-DR, and only one was weak positive for CD10. Using probe b, SstI-Sst I segment, Southern blot analysis showed the rearrangement of BCL-1 gene in a patient with MZL. Our results suggested that t(11;14) is found in lymphoid malignancies with mature B-cell phenotype and that hepatosplenomegaly, gastrointestinal involvement, leukemic manifestation, and poor prognosis are common clinical features.

Aged↗

[Aggressive myeloma with subcutaneous tumor and pericardial involvement].

A 67-year-old male was admitted to our hospital because of anemia, thrombocytopenia, and renal failure. On admission he showed splenomegaly and elevated serum LDH level. Bone marrow showed hypercellularity with massive infiltration of lymphoblastoid cells. He was diagnosed as having multiple myeloma (BJ-kappa, stage IIIB). He transiently responded to intensive chemotherapy (VAD, MP, IFN alpha) but relapsed with multiple subcutaneous tumors and pericardial effusion. This is a rare case that the myeloma cell invasion to pericardial space was diagnosed before his death. The level of interleukin 6 (IL-6) in pericardial effusion was 16382 pg/ml, and the myeloma cells obtained from the pericardial effusion responded to IL-6, which suggested that high level of IL-6 closely related to the proliferation of myeloma cells in this case.

Aged↗

Analysis of mutations and expression of GAP-related domain of the neurofibromatosis type 1 (NF1) gene in the progression of chronic myelogenous leukemia.

We investigated mutations in the GTPase activating protein-related domain of the neurofibromatosis type 1 gene (NF1-GRD) and its expression in each phase of chronic myelogenous leukemia (CML). Samples from 45 cases in chronic phase (CP), 41 in acute phase, and four CML cell lines were examined for mutations in the NF1-GRD by single-strand conformation polymorphism (SSCP) analysis and allele specific restriction analysis (ASRA). No mutations were detected in the exon where frequent mutations have recently been reported in human tumors, namely the FLR exon. We also examined for point mutations of the N-ras gene but found no mutations either. In 23 samples from CML cases and four CML cell lines, expression of two types of the NF1-GRD transcripts, type I and type II, were examined by NF1-GRD-specific polymerase chain reaction-based densitometric analysis and by the quantitative assay with coamplification of the NF1-GRD and beta-actin transcripts. Consequently, although expression level of type I transcripts varied among the samples, type II expression was increased in CML cell lines and a minor increase in type II expression was observed in the samples in acute phase compared with CP. However, this difference in type II expression between CP and acute phase was so small that changes of NF1-GRD transcripts as well as NF1-GRD or N-ras mutations might not be responsible for the progression of CML.

Alleles↗

Inversion of chromosome 16 and eosinophilia in refractory anemia with ring sideroblasts: report of a case.

A 72-year-old male who was admitted to our hospital with severe anemia was diagnosed as refractory anemia with ring sideroblasts (RARS), according to the French-American-British (FAB) classification of myelodysplastic syndromes (MDS). The patient showed persistent eosinophilia with no definite signs of either allergy or a parasitic infection. Chromosomal analysis of bone marrow cells revealed inv(16)(p13q22), a known characteristic of M4Eo acute myeloid leukemia (AML) in the FAB classification. This patient didn't exhibit leukemic transformation during his 20-month clinical course, nor was any found at autopsy. Therefore, this is the first case of RARS to speculate that the chromosomal characteristic inv(16)(p13q22) might be specific for eosinophilia rather than AML.

Aged↗

Multilineage response in aplastic anemia patients following long-term administration of filgrastim (recombinant human granulocyte colony stimulating factor).

The present multicenter study was undertaken to confirm whether filgrastim/recombinant human granulocyte colony stimulating factor (rhG-CSF) could mobilize residual multipotential stem cells by its G0-shortening effect in patients with aplastic anemia (AA) and induce a multilineage response. Twenty-seven patients with acquired severe or moderate AA received long-term administration (2 to 12+ months) of rhG-CSF in doses from 100 to 400 micrograms/body/day by s.c. injection or 250 to 1,500 micrograms/body/day by i.v. infusion. Twenty-six out of the 27 evaluable patients showed a substantial increase in neutrophils associated with a recovery of myeloid precursors in bone marrow within one month of therapy. Interestingly, 10 out of the 27 patients showed a dramatic improvement in severe anemia after two to ten months of therapy. Moreover, severe thrombocytopenia improved after two to four months of therapy in three out of these ten patients accompanied by a significant increase in megakaryocytes in bone marrow. Clonal cultures of bone marrow cells revealed a recovery in myeloid as well as erythroid precursors in most of these ten patients. In two patients who showed a trilineage response, mixed and megakaryocyte colony formations also recovered. These results suggest that long-term administration of rhG-CSF mobilizes myeloid, erythroid, megakaryocyte and multipotential progenitor cells and induces a multilineage response in some patients with AA.

Adolescent↗

Trilineage response in severe aplastic anemia following long-term therapy with recombinant human granulocyte colony-stimulating factor.

We investigated the effects of long-term therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a 69-year-old man with severe aplastic anemia (SAA). The patient was too old to receive a bone marrow transplantation, and high-dose methylprednisolone and antilymphocyte globulin were ineffective. We administered rhG-CSF in combination with metenolone acetate. Trilineage blood cell components were recovered 6 months later. These findings suggest that long-term G-CSF therapy may be beneficial in patients with SAA who are not candidates for bone marrow transplantation.

Aged↗

Recombinant human granulocyte colony-stimulating factor in combination with continuous infusion of cytosine arabinoside for the treatment of refractory acute myelogenous leukemia.

Because recombinant human granulocyte colony-stimulating factor (G-CSF) has been reported to increase the sensitivity of acute myelogenous leukemia (AML) blast cells to cytosine arabinoside (Ara-C) in vitro, we treated a patient with refractory AML with an Ara-C-based regimen in combination with G-CSF (G-CSF/Ara-C therapy). G-CSF (50 micrograms/m2/day, subcutaneous injection) was administered simultaneously with a continuous intravenous infusion of Ara-C (70 mg/m2/day). Complete remission was achieved, however, severe neutropenia, documented infection, stomatitis, and diarrhea were observed. In vitro studies using 3H-thymidine uptake and dual parameter flow-cytometric analysis of DNA and proliferating cell nuclear antigen showed that leukemic blast cells in S phase were increased after incubation with G-CSF. G-CSF also enhanced expression of the transferrin receptor (CD71) on blast cells in vitro. These observations suggest that G-CSF/Ara-C therapy may be useful in the treatment of high-risk AML.

Bone Marrow↗

[Acute basophilic leukemia: a case report].

A 56-year-old woman was admitted to our hospital in January, 1990 because of fever and petechiae. Leukocyte count of peripheral blood showed 41,000/microliters with 89% immature cells, and bone marrow was normocellular with 96.2% immature cells. They were medium to large in size, positive for peroxidase staining, CD-13 and CD-33. Half of them contained azurophilic granules. They showed metachromasia by toluidine blue, contained basophilic granules in electron microscopic examination and reacted to G-CSF, G-CSF and IL-3. She was diagnosed as acute basophilic leukemia and treated with BHAC-DMP and B triple-V regimen, but remission was not attained. She died of peritonitis due to gastrointestinal tract perforation and pneumonia in March, 1990. This is the fifteenth case of acute basophilic leukemia reported in Japan, and the hematological examinations performed in this patient were demonstrated.

Bone Marrow↗

Autoimmune thrombocytopenia following peripheral blood stem cell autografting.

A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.5 x 10(9)/l and the platelet count > 50 x 10(9)/l. The platelet count was 145 x 10(9)/l on day 20. Purpura developed on the anterior chest and legs on day 50, at which time the platelet count fell to 17 x 10(9)/l. The BM was hypocellular with an increase in megakaryocytes. Platelet-associated IgG (PAIgG) was 88.1 ng/10(7) platelets (normal range 9-25 ng/10(7)); a diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone administration led to an increase in the platelet count and a decrease in PAIgG. Analysis of lymphocyte subsets revealed an increased number of CD3+ gamma/delta T cells. It is postulated that the thrombocytopenia in this case was due to an autoimmune mechanism such as ITP.

Adult↗