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Biomedical subjects

K Muroi

Publications and source records attributed to K Muroi.

At least 37 records · Page 2Linked to original sources

Analysis of C-KIT, TIE and HTK expression on leukemic cells using flow cytometry: a preliminary report.

C-KIT, TIE and HKT expression on leukemic cells from patients were simultaneously analyzed using flow cytometry. Consistent with previous reports, leukemic cells from most patients with de novo acute myeloid leukemia (AML) were C-KIT-positive (28/35), while those from patients with B-lineage acute lymphoid leukemia (B-ALL) were C-KIT-negative (0/9). In the B-ALL patients, leukemic cells trom seven patients had one or more myeloid antigen such as CD13, CD15 and CD33. In contrast to C-KIT expression, leukemic cells from only one patient with acute monocytic leukemia were TIE-positive. Similarly, leukemic cells from only two patients (one, B-ALL with t(4;11)(q21;q23) and one, essential thrombocythemia in myeloblastic transformation (ET-MBT)) were HTK-positive. These results suggest that among the three receptor tyrosine kinases, C-KIT is the most useful marker for identifying AML.

Antibodies, Monoclonal↗

Expression profiles of I and sialosyl-I antigens on blood cells: the sialosyl-I antigen is expressed along the monocytic differentiation.

Expression of I and sialosyl-I antigens was examined using specific monoclonal antibodies. The anti-I antibody C6 reacted with monocytes (24%), T cells (55%), B cells (80%) but not with neutrophils (4%), bone marrow (BM) CD34+ cells (2%) or mobilized peripheral blood (PB) CD34+ cells (1%). The anti-sialosyl-I antibody NUH2 reacted with monocytes (38%) and BM CD34+ cells (41%) but not with T cells (2%), B cells (0%) or neutrophils (1%) and it hardly reacted with mobilized PB CD34+ cells (8%). Flow cytometric analyses of CD34+ cells enriched from BM showed that most of the sialosyl-I cells expressed CD13, CD33, CD117, and HLA-DR. Sialosyl-I+ CD34+ cells isolated from BM produced a large number of granulocyte-macrophage colonies and macrophage colonies. Therefore, sialosyl-I+ CD34+ cells are suggested to be colony-forming units granulocyte-macrophage (CFU-GM) and colony-forming units macrophage (CFU-M). BM CD34+ cells cultured in medium containing cytokines produced I+ CD14+ monoblasts and sialosyl-I+ CD14+ monoblasts. Leukemic cells from patients with acute myeloid leukemia were I-negative (32/32) and sialosyl-I-positive (one/32). Leukemic cells from patients with acute lymphoid leukemia were I-positive (four/ten) and sialosyl-I-negative (ten/ten). These results indicate that (1) the I antigen is broadly expressed by monoblasts, monocytes, lymphocytes, and leukemic lymphoblasts, and (2) the sialosyl-I antigen is expressed along the normal differentiation of CFU-GM to monocytes.

Antibodies, Monoclonal↗

Analysis of peripheral blood CD34+ cells mobilized with granulocyte colony-stimulating factor (G-CSF) using a long-term culture system.

G-CSF administered to healthy volunteers at a dose of 3 microg/kg for 5 days mobilized colony-forming units granulocyte-macrophage (CFU-GM), burst-forming units-erythroid (BFU-E), and long-term culture-initiating cells (LTC-IC) to a maximal level on day 4 or 5. To determine the number of primitive hematopoietic progenitors in the peripheral blood, mononuclear cells (MNCs) or CD34+ cells were cultured in a long-term culture (LTC) system. We defined the colonies produced by cells during LTC at week 2 as differentiated progenitors and those at week 5 as primitive progenitors. G-CSF administered to healthy volunteers increased the number of differentiated progenitors from day 4 and primitive progenitors on days 3-5. Enriched CD34+ cells from healthy volunteers treated with G-CSF (PB-G) or without it (PB-SS), and patients treated with chemotherapy plus G-CSF (PB-CG) were subjected to LTC for 7 weeks. PB CD34+ cells from PB-G contained less primitive progenitors than those from PB-CG. Therefore, in healthy donors administered G-CSF at a dose of 3 microg/kg, the number of PB CD34+ cells should be harvested as much as possible to perform allogeneic peripheral blood stem cell transplantation (PBSCT).

Antigens, CD34↗

[Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia].

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Aclarubicin↗

Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991-96.

Twenty cases of interstitial pneumonia secondary to treatment with granulocyte colony-stimulating factor (G-CSF) were reviewed. Their interstitial pneumonia had the following features: (a) it occurred predominantly in patients aged 60 years or older; (b) it was prevalent among patients with haematological malignancies, particularly non-Hodgkin's lymphoma; (c) in all patients G-CSF was given after anti-cancer agents with potential to affect the lungs; (d) at the onset, many patients had symptoms such as dyspnoea and fever; and (e) the leucocyte (neutrophil) count as well as lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were usually higher than normal at the onset. These findings indicate that, when G-CSF is used in combination with pneumotoxic anti-cancer agents, respiratory function should be monitored before and during treatment. If the leucocyte (or neutrophil) count and/or LDH and CRP increase suddenly in association with dyspnoea and fever during administration of G-CSF, interstitial pneumonia should be suspected. Accordingly, a chest radiograph and pulmonary functional tests should be performed promptly. If a diagnosis of interstitial pneumonia is made, steroid pulse therapy should be commenced immediately.

Adult↗

Expression of sialosyl-T and disialosyl-T antigens in erythroid cells.

Expression of T, sialosyl-T and disialosyl-T antigens on normal blood and bone marrow cells as well as transformed cells was examined using specific monoclonal antibodies and multidimensional flow cytometry. Both anti-sialosyl-T (QSH1) and anti-disialosyl-T (QSH2) monoclonal antibodies aggregated erythrocytes. The anti-disialosyl-T antibody was specific for the erythroid lineage and did not react with neutrophils, monocytes or T-lymphocytes, while the anti-sialosyl-T antibody reacted with erythroid cells and a subset of T-lymphocytes. The developing erythroid cells in bone marrow showed coordinate expression of glycophorin A and the two carbohydrate chains, sialosyl-T and disialosyl-T. Analysis of neoplastic cells showed that the anti-disialosyl-T antibody only reacted with glycophorin A-positive blasts from erythroleukemia (FAB M6) patients (4/4) and one patient with chronic myeloid leukemia in erythroblastic transformation (CMLET). Leukemic blasts from these patients demonstrated coordinate quantitative expression of glycophorin A and disialosyl-T. The anti-sialosyl-T antibody reacted with glycophorin A-positive blasts from FAB M6 patients (4/4) and one CMLET patient; however, the antibody also reacted with glycophorin A-negative blasts from one FAB M6 and the one CMLET patients and transformed cells from other types of leukemia. The anti-T monoclonal antibody (HH8) did not react with any of the other cells tested. These results indicate that glycophorin A and disialosyl-T expression are tightly linked during normal erythroid development and erythroid leukemogenesis.

Antigens, Surface↗

[Acute myeloid leukemia with monosomy 7 accompanied by central diabetes insipidus].

A 27-year-old female was diagnosed as having atypical aplastic anemia in 1979 because of hypercellular bone marrow with abnormal erythroblasts and megakaryocytes. Afterward the diagnosis was corrected to myelodysplastic syndrome (RA) due to the reevaluation of the bone marrow smears. In March, 1995, thirst and polyurea occurred. In April, 1995, bone marrow aspiration biopsy showed the proliferation of atypical blasts (28%), and two months later, the number of the blasts increased (30%) and leukemic progression was noticed. Only 0.5 percent of the blasts showed weak peroxidase activity, and most of the blasts had CD13, CD33 and several adhesion molecules as CD11a, CD11b, CD44, CD54 and CD56. Karyotype of the bone marrow cells was 45, XX, -7. Her polyurea was caused by central diabetes insipidus. She was also complicated by pleuritis, colon ulcer, sinusitis and hypothalamic dysfunction. The etiology of these signs was due to the leukemic cell infiltration. She died despite of receiving multi-drug chemotherapy.

Adult↗

[Clinicopathological features in HLA-DR-negative acute myeloid leukemia].

From a series of 176 patients with acute myeloid leukemia (AML), we have identified 11 patients with HLA-DR-negative AML excluding acute promyelocytic leukemia. All patients showed not (15; 17) or consistent chromosomal abnormalities. According to the French-British-American criteria, seven, three, and one patients were classified into M1, M2, and M4, respectively. Blasts from these patients were CD33+, HLA-DR-, and lymphoid-antigen-. All patients entered complete remission after induction therapy. Of these, blasts from four patients had strikingly invaginated nuclear membrane and finely granular peroxidase activity. The phenotype of the blasts was CD33+, CD34-, CD2-, and HLA-DR-. All four patients showed hyperleukocytosis on initial presentation. One patient received all-trans retinoic acid at relapse, however, the drug did not induce the differentiation of the blasts. These four patients were suspected to have acute myeloid/natural killer (NK) leukemia because of the prominent morphological feature of the blasts and the initial hyperleukocytosis, although NK cell activity of the blasts was not examined. Since HLA-DR-negative AML is heterogeneous, it is necessary for identifying acute myeloid/ NK leukemia within the disorder.

Adult↗

[Double autologous peripheral blood stem cell transplantation (double APBSCT) for lymphoblastic lymphoma].

A 24-year-old male was admitted to our hospital, complaining of right back pain, in May 1995. Chest X-ray films showed an abnormal mass in the mediastinum. Computed tomography revealed massive effusion in the pleural and pericardial space. A biopsy specimen of the pleural lesion demonstrated lymphoblastic lymphoma of T cell type. After the completion of intensive chemotherapy by our original protocol, he entered into partial remission. Peripheral blood stem cells (PBSC) were harvested using a high-dose cytarabine (Ara-C) followed by granulocyte-colony stimulating factor (G-CSF) mobilization regimen. The total number of collected PBSC was enough to perform two courses of PBSCT. In January 1996, following the conditioning regimen of nimustine hydrochloride, etoposide (VP-16), Ara-C, thiotepa, he received PBSCT. Complete remission was achieved after the 1st PBSCT. In March 1996, he received the 2nd PBSCT following the conditioning regimen of carboplatin, VP-16, ifosfamide. No regimen-related toxity or delayed engrafment was observed. Subsequently, he received irradiation to his neck and mediastinum, the primary site of the disease. As of February 1997, he has no evidence of the disease.

Adult↗

Therapy-related leukemia with a novel 21q22 rearrangement.

We present a case of a 59-year-old Japanese man with therapy-related acute myeloblastic leukemia (AML) after the chemotherapy for non-Hodgkin's lymphoma (NHL). Accumulated doses of cyclophosphamide, procarbazine, doxorubicin, mitoxantrone, and etoposide were 18,300 mg, 3000 mg, 580 mg, 100 mg, and 4150 mg, respectively, which had been administered for the treatment of NHL. Myeloblasts in the peripheral blood increased 43 months after the onset of NHL. He was diagnosed as having AML (M2; FAB classification). The karyotype of the bone marrow cells in the present case contained the following abnormalities: t(2;21)(q21;q22), t(8;21)(q22;q22), and add(13)(q34). In the present case, 645 base pairs of chimeric mRNA were detected by reverse transcription-polymerase chain reaction, indicating the presence of AML1/MTG8 rearrangement. Translocation (2;21)(q21;q22) has not been described previously to our knowledge. It is interesting that the breakpoint of 21q22 existed both in t(2;21) and t(8;21). The disrupted AML1 gene resulting from two 21q22 rearrangements may be involved in the pathogenesis of AML in the present case. The clinical importance of therapy-related AML having the 21q22 rearrangement remains to be examined.

Aclarubicin↗

Therapy-related chronic myelomonocytic leukaemia with bone marrow eosinophilia associated with der(11)t(1;11)(q21;q14).

A 19-year-old male with chronic myelomonocytic leukaemia (CMML) with bone marrow eosinophilia terminating in myeloblastic transformation is described. Before the appearance of CMML, he received a total dose of 2,894 mg of nimustine for the treatment of a pontine glioma over 12 years. Peripheral blood count showed leucocytosis with mature neutrophils and monocytes. Bone marrow smears showed myeloid hyperplasia with increased blasts and abnormal eosinophils and dysplastic features in the myeloid and megakaryocytic cells. A karyotype analysis of the bone marrow cells indicated 46, XY, der(11)t(1;11)(q21;q14). No bcr/abl rearrangement was observed in the cells. He was treated with hydroxyurea to control the leucocyte count, but myeloblastic transformation developed.

Antineoplastic Agents↗

[Retrospective analysis on 21 patients with follicular lymphoma].

We retrospectively analyzed the clinical data of the 21 patients with follicular lymphoma admitted to our institution from 1977 to 1994. The frequency of follicular lymphoma was 9.1% in the 231 patients with non-Hodgkin's lymphoma. Overall survival rates at 1 year, 3 years, and 5 years were 90.2%, 78.2%, and 52.1%, respectively. The median follow-up of surviving patients and time to treatment failure (TTF) was 43 months and 30 months, respectively. The median time from disease progression to death was 171 days. In univariate analysis, factors associated with poor survival were stage IV (Ann Arbor staging system), anemia (hemoglobin level less than 10g/dl), bone marrow involvement, two or more extranodal sites, and failure in induction of complete remission (CR) in the entire course. Factors associated with short TTF were anemia, bone marrow involvement, and failure in induction of CR. In multivariate analysis, induction of CR affected survival and TTF independently.

Adult↗