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Biomedical subjects

C Shimazaki

Publications and source records attributed to C Shimazaki.

At least 145 records · Page 8Linked to original sources

Immunophenotypic analysis of lymphocytes and myeloma cells in patients with multiple myeloma.

The immunological phenotypes of lymphocytes and myeloma cells in 48 patients with multiple myeloma (MM) were analyzed using a panel of monoclonal antibodies (mAbs). Myeloma cells were positive for OKT10, BL3, PCA1 and BA2. In a few cases, they were also positive for the B cell-associated antigens J5, B1 and I2. Eight of 48 cases had more than 15% J5-positive lymphocytes, and some lymphocytes in MM expressed plasma cell-associated antigens (PCA1, BL3, OKT10), suggesting a possible clonal involvement. These observations demonstrate the heterogeneity of surface antigen expression of myeloma cells and suggest that BL3, PCA1, BA2 and J5 may be useful mAbs for purging myeloma cells from bone marrow for autologous transplantation.

Antibodies, Monoclonal↗

[Diclonal gammopathy (IgG kappa, IgA lambda) with nephrotic syndrome terminating into IgA lambda myeloma after three years--report of a case].

A 43-year-old man was admitted to our hospital because of legs edema and periorbital edema in Dec. 1983. Laboratory findings showed massive proteinuria (3.7 g/day), Bence Jones protein (BJP) in urine, and hypoproteinemia. Peripheral blood examinations were normal and a bone marrow aspiration showed hypocellularity with slight increase of monocytes and plasma cells. Serum immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda). Serum IgG was 1,690 mg/dl, IgA 379 mg/dl and IgM 160 mg/dl. No remarkable findings were obtained in bone survey, Ga-scintigraphy and rectal biopsy, and a diagnosis of diclonal gammopathy with nephrotic syndrome was made. In Aug. 1986, serum IgA started to increase rapidly with concomitant decrease IgG. He died of pneumonia due to pancytopenia in Dec. 1986, when serum IgG was 450 mg/dl, IgA 1,014 mg/dl, and IgM less than 39 mg/dl. Immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda) in serum and BEP (kappa, lambda), IgG (kappa) and IgA (lambda) in urine. An autopsy showed massive infiltration of myeloma cells which were positive for lambda light chain in bone marrow, suggesting a development of myeloma from a diclonal gammopathy in about 3 years.

Adult↗

Photoradiation methods for purging autologous bone marrow grafts.

The potential of various photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants is discussed in this paper. The results with fluorescent dyes, Dihematoporphyrin Ether (DHE) and Merocyanine-540 (MC-540) are detailed. Following photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity towards lymphoid and myeloid neoplastic cells, but had significantly less effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, cALLa positive acute lymphoblastic leukemia (Reh), and diffuse histiocytic B-cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 ug/ml and MC-540 concentrations of 15 to 20 ug/ml, clonogenic tumor cells could be reduced by more than 4 logs, when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells, and on normal marrow myeloid (CFU-GM) precursors, when the drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15-20 ug/ml) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). Using DHE (2.5 ug/ml), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared, following sequential drug and light exposure of cells, while simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. The data from various centers is briefly discussed with special emphasis on clinical trials. Our results provide a useful model for leukemia and lymphoma cells and suggest that these phototherapy experiments can be implemented into clinical trials.

Bone Marrow↗

Molecular analysis of T cell receptor and CD3 genes in CD3- large granular lymphocytes (LGLs): evidence for the existence of CD3- LGLs committed to the T cell lineage.

Seven patients with CD3- lymphoproliferative disorder of granular lymphocytes (LDGL) were analyzed for rearrangement of the T cell receptor (TCR) delta and alpha as well as gamma and beta genes. Among those patients six showed the germline configuration of all known rearranging TCR genes. Two analyzed patients of them lacked CD3-gamma transcripts and expressed nonfunctional TCR-beta transcripts. Meanwhile, TCR-delta gene rearrangement accompanied by expression of full-length TCR-delta transcripts was observed in one patient with CD3- LDGL. In addition, the cells from this patient transcribed the CD3-gamma gene which is one of the earliest events restricted to cells committed to the T cell lineage. These findings indicate that CD3- LGLs include not only cells belonging to the NK cell lineage but also precursor cells committed to the T cell lineage.

Antigens, Differentiation, T-Lymphocyte↗

[Large granular lymphocyte leukemia containing oligoclonal EB viral DNA].

A 32-year-old female was admitted to our hospital because of abdominal fullness, jaundice and pretibial edema in November, 1987. Leukocyte count of peripheral blood showed 13300/microliters with 84% leukemic cells and bone marrow was normocellular with 63.6% leukemic cells. Leukemic cells had azurophilic large granules with basophilic cytoplasm and positive for CD 2, OKIa 1, NKH-1 and negative for CD 3, CD 4, CD 8, CD 16. T cell receptor (TCR) genes for beta, gamma and delta chain and immunoglobulin heavy chain gene were in germ line configuration. These cells also had natural killer (NK) activity and antibody dependent cell mediated cytotoxicity (ADCC) activity. These observations suggested that they were derived from NK cell lineage. It is often difficult to demonstrate their clonalities in lymphoproliferative disorder of granular lymphocytes (LDGL). In the present case, the analysis of EBV genome using termini probe demonstrated polyclonal bands, while we found constant chromosome abnormalities; 47 XX, +3. From these observations, this case was considered to have several clones, and one of which could be detected by chromosome analysis. The analysis of EBV genome using termini probe may be useful to demonstrate their clonalities in LDGL in addition to conventional chromosome analysis.

Adult↗

[Effect of combination therapy with carumonam and clindamycin on severe infections in patients with hematologic malignancies].

We evaluated the efficacy of a combination therapy with carumonam (CRMN) and clindamycin (CLDM) on severe infections in patients with hematologic malignancies. Fifty three patients were included in this study. The efficacy of the combination therapy was evaluated according to the criteria by TAKAKU et al. Fourteen cases were evaluated as excellent, and 24 cases were as good, with a total rate of effectiveness of 71.7% (38/53). It should be noted that the rate of effectiveness in patients having less than 100/microliters neutrophils was 77.3% (17/22). Adverse effects were observed in 2 patients (3.7%). One case was hepatotoxicity and the other was nephrotoxicity. Both were mild and transient, however. These observations suggested that the combination therapy with CRMN and CLDM was effective and safe for the treatment of severe infections in patients with hematologic malignancies.

Adult↗

[A case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia associated with chronic renal failure].

A rare case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) associated with chronic renal failure was described in this report. A 73-year-old male was admitted and diagnosed as IPL. IPL is proposed by Mori et al. in 1980. Clinical entity of IPL is (1) Polyclonal hyperimmunoglobulinemia (2) Systemic Lymphadenopathy characterized by remarkable mature plasmacytosis without atypism and by no destruction of the structures. (3) All disease with polyclonal hyperimmunoglobulinemia can be excluded. In this patient, physical findings showed enlarged lymph nodes (1-2 cm) in bilateral nuchal, submandibular, axillary and inguinal lesions. Laboratory examinations showed polyclonal hyperimmunoglobulinemia (especially IgG, IgA), anemia and renal dysfunction. Microscopic observation of hematoxylin-eosin staining in the axillary lymph node showed increased mature plasma cells without evidence of malignant growth. Immunoperoxidase staining showed intracytoplasmatic polyclonal immunoglobulins. IPL is known as invading other organs besides lymph node, for example skin, lung or kidney. This patient showed renal dysfunction (Cr clearance 11 ml/min, severe proteinuria). Nine cases of IPL and multicentric plasma cell type Giant Lymphnode Hyperplasia (GLH) concurrent with renal dysfunction were reported. Only in two of them chronic renal failure were reported. Twice a week hemodialysis improved his condition and laboratory findings.

Aged↗

[Malignant lymphoma associated with Addison's disease].

A 62-year-old man was admitted to our hospital in Oct. 1986, because of easy fatigability, generalized pigmentation and lymph node swelling. Radiological examination showed massive adrenal tumor and two lung tumors. Endocrinological findings showed cortisol 8.3 micrograms/dl, aldosterone 35.3 ng/dl, ACTH 348 pg/ml, and non reacting pattern was observed in ACTH-overloading test, suggesting a presence of Addison's disease. A diagnosis of malignant lymphoma (Non-Hodgkin's lymphoma, diffuse large cell type) was made by lymph node biopsy, and radiotherapy to bulky bilateral adrenal tumors and cervical lymph nodes was performed with some response. Then, treatment with VEPA and PEP-VP regimens were carried out, and adrenal tumor became remarkably small in size. However, adrenal function did not recover. He relapsed in Jan. 1987 and died of multiple organ failure.

Addison Disease↗

Ex vivo treatment of myeloma cells by 4-HC, VP-16, LAK cells and antibodies.

To assess the usefulness of 4-hydroperoxycyclophosphamide (4-HC) and Etoposide (VP-16) as a purging agent for myeloma cells in bone marrow ex-vivo, myeloma cell lines (SK-RCS-1, RPMI-8226), lymphoma cell line (SK-DHL-2) and normal bone marrow (BM) cells were treated at different concentrations of 4-HC, VP-16. In separate experiments, LAK cells or antibodies were also used to treat the above cell lines. Clonogenic tumor cells from all three cell lines could be reduced by more than 4 logs, when treated alone or as a mixture with irradiated normal bone marrow cells at a 4-HC concentration of 60 mumol/l. Under similar conditions, approximately 1% of normal BM myeloid progenitor granulocyte-macrophage colony forming cells (CFU-GM) survived. The results with LAK cells and antibodies were also encouraging. These observations support the use of various purging methods for myeloma cells for autologous bone marrow transplantation.

Antibodies, Monoclonal↗

Clinical and cytogenetic features in six patients with chronic myelogenous leukemia and a complex Philadelphia translocation.

Six patients with chronic myelogenous leukemia and a complex Philadelphia (Ph1) translocation are described. The complex Ph1 translocations were a three-way translocation in five patients and a five-way translocation in one. Additional chromosomal aberrations were detected in four of five patients when the blastic crisis supervened. The median survival time was 42 months. The remaining patient died of acute myocardial infarction 23.5 months after the diagnosis of CML was made. There seems no difference between these six patients and those with the standard Ph1 with respect to clinical, hematologic and cytogenetic findings.

Adolescent↗

[T cell receptor delta chain gene rearrangement in acute unclassified leukemia].

A 31 year-old male who was treated with radiation under the diagnosis of malignant lymphoma was admitted to our hospital because of systemic erythema and tumor of bilateral upper arms in October, 1987. Leucocyte count of peripheral blood showed 4,400/microliters with 36% leukemic cells and bone marrow was hypercellular with 85.6% leukemic cells. Leukemic cells were negative for peroxidase reaction and lineage specific monoclonal antibodies such as CD3, CD4, CD8, CD10, CD19 and CD20. T cell receptor (TCR) delta gene was rearranged but TCR beta, TCR gamma and immunoglobulin (Ig) genes were in germline configuration. He was treated with combination regimen of doxorubicin, vindesine, prednisolone and L-asparaginase, and complete remission was obtained. These observations suggest that TCR delta gene rearrangement is useful for determination of clonality in cases without rearrangements of the other TCR and Ig genes.

Acute Disease↗

[Triploid clone observed at blastic crisis in chronic myelogenous leukemia with complex Ph1 translocation (9; 22; 12)].

A 56-year-old female, who was diagnosed as CML in 1983 and had been well controlled with busulfan, was admitted to our hospital because of fever and iliac bone pain. Peripheral blood showed leukocytosis (WBC 70,000/microliters and bone marrow was normocellular with 53% leukemic cells, suggesting that she was in the blastic crisis. Chromosomal analysis of bone marrow cells at that time revealed t (9; 22; 12) and some additional abnormalities. The number of chromosomes ranged from 44 to 131 and the mode of chromosome number was 65. She was treated with combination regimen consisting of vincristine, 6-mercaptopurine and prednisolone and right iliac tumor was irradiated. Three months after admission, she died of DIC and pulmonary insufficiency due to leukemic infiltration.

Blast Crisis↗

[Double minute chromosomes (DMs) in a case of acute myelomonocytic leukemia].

A 71-year old male was admitted to our hospital because of general malaise and fever. Peripheral blood showed Hb 8.1 g/dl, platelet 7.0 X 10(4)/microliters, and WBC 18.100/microliters with 64% leukemic cells. Bone marrow showed normocellularity with 73.4% leukemic cells. They were positive for peroxidase and alpha-naphthyl butyrate esterase stainings. Serum and urine lysozyme levels were elevated. He was diagnosed as having acute myelomonocytic leukemia (M 4 in FAB classification). Chromosome analysis of bone marrow cells showed 45, XY, -17, t (9; 17) (q22; p13) and double minute chromosomes (DMs) were observed in the 50 cells analyzed. A complete remission (CR) was obtained by DCMP regimen, but he relapsed as acute monocytic leukemia (M 5 b in FAB classification) and died 5 months after diagnosis. DMs appear to be rare in acute leukemia and the clinical and etiologic implications of DMs are discussed.

Aged↗