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Biomedical subjects

T Amenomori

Publications and source records attributed to T Amenomori.

At least 19 recordsLinked to original sources
PubMed2001

De novo acute myeloid leukemia in the elderly; a consistent fraction of long-term survivors by standard-dose chemotherapy.

To clarify the characteristics of de novo acute myeloid leukemia (AML) among the elderly, we reviewed 112 patients over 60 years old (median age 72 years) who were treated at hospitals in Nagasaki Prefecture with a population of 1.5 million between 1987 and 1994. Reclassification of morphological diagnosis revealed that the proportion of M3 was lower but that of M6 and the incidence of cases with trilineage dysplasia (TLD), known as poor prognostic features, were higher in the elderly than in patients less than 60 years old. Similarly, chromosomal data showed a lower frequency of favorable karyotypes such as t(8;21) and t(15;17) in the elderly. The overall survival of all 112 patients was 10.3% at 5 years. Multivariate analysis indicated that good performance status (PS), low WBC at diagnosis, standard dose multi-drug chemotherapy and all-trans retinoic acid (ATRA) treatment for M3 patients, and morphological findings without TLD were significantly correlated with longer survival. Most of the long-term survivors were found among those who received standard dose therapy in this series, although no consensus has been established how to treat elderly AML patients. We propose that a prospective controlled trial is necessary to confirm the role of standard dose chemotherapy for elderly patients with de novo AML.

Acute Disease↗
PubMed1998

Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes.

Among acquired stem cell disorders, pathological links between myelodysplastic syndromes (MDS) and aplastic anaemia (AA), and paroxysmal nocturnal haemoglobinuria (PNH) and AA, have been often described, whereas the relationship between MDS and PNH is still unclear. We analysed blood cells of patients with MDS to determine the incidence of the PNH clone, and analysed the PIG-A gene to find mutations characteristic of the PNH clone in MDS. In four (10%) of 40 patients with MDS, flow cytometry showed affected erythrocytes and granulocytes negative for decay-accelerating factor (DAF) and CD59. The population of affected erythrocytes was smaller in MDS patients with PNH clone (MDS/PNH) than in patients with de novo PNH, and haemolysis was milder in the MDS/PNH patients. PIG-A mutations were found in granulocytes of all patients with MDS/PNH. In type and site, the PIG-A mutations were heterogeneous, similar to that observed in de novo PNH; i.e. no mutation specific to MDS/PNH was identified. Of note, three of four patients with MDS/PNH each had two PNH clones with different PIG-A mutations, suggesting that PIG-A is mutable in patients with MDS/PNH. In a MDS/PNH patient with trisomy 8, FISH detected a distinct karyotype in a portion of granulocytes with PNH phenotype, indicating that PNH and MDS partly shared affected cells. Thus, MDS predisposes to PNH by creating conditions favourable to the genesis of PNH clone. Considering the increasing prevalence and incidence of MDS, these disorders could be useful for investigating the mechanism by which PIG-A mutation is induced.

Adolescent↗
PubMed1996

Progression from myelodysplastic syndrome to acute lymphoblastic leukaemia with Philadelphia chromosome and p190 BCR-ABL transcript.

We describe a patient with Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukaemia (ALL) who developed it 2.5 years after being diagnosed with myelodysplastic syndrome (MDS). The patient initially had refractory anaemia (RA), but progressed to refractory anaemia with excess blasts (RAEB) 2 years later, that terminated in ALL. An immunophenotypic analysis of the lymphoblasts revealed CD10 and CD19 positive cells. The karyotype was normal 46,XY in RA phase, 46,XY,20q-during the RAEB phase, and 46,XY,t(9;22)(q34;q11),20q-during the ALL phase. Furthermore, p190 BCR-ABL mRNA was detected in the ALL blasts. These findings indicate that this ALL arose from the MDS clone through multiple cytogenetic evolutions, the final event of which was the acquisition of p190 BCR-ABL type Ph1.

Base Sequence↗
PubMed1993

Peripheral nerve lesions in HTLV-I associated myelopathy (HAM/TSP).

Peripheral nerve dysfunction (PND) was found in as many as 43% of our patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM/TSP). To evaluate the PND further we biopsied the sural nerve in 6 patients. The histological features were varying degrees of demyelination, remyelination, axonal atrophy and degeneration, and perineurial fibrosis. "Globule" or "sausage" formation was prominent in two of the specimens. Inflammatory infiltrates were absent. No deposits of IgG, IgM, IgA, or complement were detected in the biopsies. No viral antigen or proviral DNA was detected. It is proposed that the PND and the histological findings noted are part of HTLV-I-associated disease and not an unrelated disorder. The pathogenesis of the PND remains unclear. There was no evidence of direct viral infection. The histological findings could represent primary changes induced by viral-triggered release of soluble factors, such as cytokines or secondary changes to more proximal disease, e.g., root involvement.

Adult↗
PubMed1993

Cytogenetic studies of non-lymphocytic neoplasias using hematopoietic growth factors: GM-CSF provides pronounced mitotic increase and improvement of the quality of banded chromosomes compared to G-CSF.

Thirty patients with a variety of non-lymphocytic neoplasias were studied cytogenetically using short-term liquid cultures of bone marrow or peripheral blood cells with or without either granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF). The final concentration of these growth factors was 10 ng/ml and the duration of culture was 48 h, since these provided optimal increases in mitotic index (MI). In GM-CSF-stimulated culture, 23 out of the 30 patients (77%) had a significantly (p < 0.05) higher MI than that in unstimulated culture, whereas only five (17%) did so in G-CSF-stimulated culture. The quality of banded chromosomes was considerably good in 17 out of the 30 patients (57%) with GM-CSF, whereas it was so only in two (7%) and three (10%) patients with no CSF and G-CSF, respectively. Of the 30 patients, 27 (90%) had the same chromosomal findings with G-CSF/GM-CSF as without CSF, but the remaining three (10%) showed a remarkable change after stimulation. Culture for 72 h with G-CSF or GM-CSF disclosed a minor abnormal clone which was undetected in 24 and 48 h cultures in a patient with myelofibrosis with myeloid metaplasia. Thus, compared with G-CSF, adding GM-CSF to cell culture may be useful for cytogenetic studies of non-lymphocytic neoplasias. The chromosomal findings may, however, be changed by these growth factors for some patients.

Chromosome Aberrations↗
PubMed1991

IL-6 production by human T lymphocytes. Expression in HTLV-1-infected but not in normal T cells.

IL-6 is an important regulator of humoral and cellular immunity. Although this cytokine is produced by diverse cell types, it is not known whether it is produced by T lymphocytes under physiologic conditions or which agents can induce T cell expression of IL-6. We analyzed the production of IL-6 by human peripheral blood T cells, human thymocytes, and human T cell lines. In pure populations of these cells, stimulated with different combinations of various mitogens and cytokines, IL-6 activity could not be detected. Analysis of purified T-alpha beta and T-gamma delta cells showed that neither T cell subset produced IL-6. Similarly, IL-6 mRNA was not detected in T cell or thymocyte populations for up to 48 h after stimulation. With the use of a PCR assay, IL-6 mRNA in T cells was found to be virtually negligible, and did not change after T cell activation. By in situ hybridization it was shown that the cells expressing IL-6 mRNA after mitogen activation of PBMC do not belong to the T cell lineage. To analyze whether human T cells express IL-6 in vivo, we examined lymphoid tissues by in situ hybridization. In normal human thymus there was no detectable signal for IL-6. Tonsils showed only few positive cells within the parenchyma, but strong expression of IL-6 by epithelial cells in crypts. In contrast to normal lymph node, which contained only rare cells positive for IL-6, a lymph node from a patient with Castleman's disease showed IL-6 expression in cells occupying the marginal sinus and interfollicular areas. Screening of various human T cell lines showed that all cell lines infected with HTLV-1 secrete IL-6 activity and express IL-6 mRNA. In addition, in vitro infection of peripheral blood T cells with HTLV-1 induced de novo synthesis and secretion of IL-6. Furthermore, IL-6 expression in HTLV-1-infected cells was enhanced by stimulation with IL-1 beta or TNF-alpha. In contrast, IL-6 was not detectable in non-infected T cell lines. These studies indicate that IL-6 may not be a physiologic product of human T lymphocytes and that infection of T cells with HTLV-1 results in aberrant expression of this cytokine.

Cell Line↗
PubMed1991

HTLV-I-associated myelopathy: clinicopathologic correlation with localization of provirus to spinal cord.

A 49-year-old South African man developed a rapidly progressive myelopathy 14 months after blood transfusion and died 1 year after the onset of symptoms. Detailed pathologic examination of the spinal cord was consistent with the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although no HTLV-I viral particles, antigens, or nucleic acids were detected in situ, polymerase chain reaction assays revealed HTLV-I proviral DNA in cervical, thoracic, and lumbar levels of the spinal cord, with the greatest amount being detected at the thoracic level. These findings suggest that the pathogenesis of HAM/TSP depends on direct infection of neural or immune elements within the spinal cord.

DNA, Viral↗
PubMed1991

Atomic bomb and leukemia.

Characteristic features of the leukemia among atomic bomb survivors were studied. Dose estimates of atomic bomb radiation were based on T65D, but the new dosimetry system DS86 was used for some analyses. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic to atomic bomb radiation induced leukemia. The threshold of CML occurrence in Hiroshima is likely to be between 0.5-0.09 Gy. However, the threshold of acute leukemia appears to be nearly 1 Gy. In the distribution of AML subtypes by FAB classification, there was no M3 case in 1 Gy or more group, although several atypical AML cases of survivors were observed. Although aplastic anemia has not increased as a late effect of the atomic bomb radiation exposure, many atypical leukemia or other myeloproliferative diseases who had been diagnosed as aplastic anemia or its related diseases have been experienced among atomic bomb survivors. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral T-cells in several atomic bomb survivors.

Humans↗
PubMed1991

Atomic bomb and leukemia.

Characteristic features of leukemia among atomic bomb survivors were studied. The ratio of a single leukemia type to all leukemias was highest for CML in Hiroshima, and the occurrence of CML was thought to be most characteristic for atomic bomb radiation induced leukemia. In the distribution of AML subtypes of FAB classification, there was no M3 cases in 1Gy or more group, although several atypical AML cases of survivors were observed. Chromosome study was conducted using colony forming cells induced by hemopoietic stem cells of peripheral blood of proximal survivors. Same chromosome aberrations were observed in colony forming cells and peripheral blood of proximal survivors.

Humans↗
PubMed1989

[Study on pathophysiology of the myelodysplastic syndromes (MDS)--pattern of dysmegakaryopoiesis related to leukemic transformation].

A series of 116 patients with MDS consisted of 74 cases of RA, 10 cases of RARS, 14 cases of RAEB, 9 cases of RAEB-T and 9 cases of CMML, were studied on the quantity and morphological abnormalities of megakaryocytes in relation to over all survival and leukemic change. The amount of megakaryocytes was graded into four groups; marked hypoplasia (O), moderate hypoplasia (L), normoplasia (N) and hyperplasia (H), RA cases showed heterogeneous pattern; containing 14 cases (18.9%) of group (O), 18 cases (24.3%) of group (L), 31 cases (41.9%) of group (N) and 11 cases (14.9%) of group (H). RARS, RAEB, RAEB-T and CMML cases were classified into group (N) or group (H). The heterogeneous pattern of RA did not relate to leukemic change, but over all survival tended to be shorter in group (N) cases. A significant number of young female cases of RA were involved in group (O). Morphological abnormalities of MDS megakaryocytes were classified into five types; I, mononuclear micromegakaryocytes, II, binuclear micromegakaryocytes, III, mononuclear small megakaryocytes, IV, multiseparated-nuclear megakaryocytes and V, megakaryocytes with bizzare nuclei. RAEB and RAEB-T cases uniformly showed marked dysmegakaryopoiesis ranging from type I to V. whereas RA, RARS and CMML cases showed mild dysmegakaryopoiesis. Only five cases (6.4%) of RA cases had type I micromegakaryocytes. Eight RA cases with type I on diagnosis or obtaining it during the clinical course tended to develop acute myeloid leukemia (5 cases) or to transform to RAEB sooner or later. In two cases of RAEB in which hematological improvement was obtained with low dose cytosine arabinoside regimen, disappearance of type I micromegakaryocytes was noted. A female case with 5q-anomaly surviving more than 10 years showed marked megakaryocyte hyperplasia and almost exclusively type III and IV megakaryocytes. These findings indicated that pattern of dysmegakaryopoiesis, especially appearance of type I, was closely related to leukemic change in MDS. Thus quantitative and qualitative evaluations of MDS megakaryocytopoiesis seemed important to understand the further heterogeneity of pathophysiology in MDS subtypes.

Aged↗
PubMed1988

Growth and differentiation of circulating hemopoietic stem cells with atomic bomb irradiation-induced chromosome abnormalities.

The effects of atomic bomb irradiation on hemopoietic stem cells were studied cytogenetically using single colonies derived from hemopoietic progenitor cells. The subjects studied were 21 healthy atomic bomb survivors (10 males and 11 females) in the high dose exposure group (100+ rad) with a known high incidence (10% or more) of radiation-induced chromosome abnormalities in their peripheral blood lymphocytes (stimulated with phytohemagglutinin), and 11 nonexposed healthy controls (5 males and 6 females). Colony formation by circulating granulocyte-macrophage (GM-CFC) and erythroid (BFU-E) progenitor cells was made by the methylcellulose method using peripheral blood mononuclear cells. Chromosome specimens were prepared from single colonies by our micromethod. The total number of colonies analyzed in the exposed group was 131 for GM-CFC and 75 for BFU-E. Chromosome abnormalities were observed in 15 (11.5%) and 9 (12.0%) colonies, respectively. In the control group, the total number of colonies analyzed was 61 for GM-CFC and 41 for BFU-E. None of these colonies showed chromosome abnormalities. The difference in incidence of chromosome abnormalities was highly significant by an exact test; p = 0.003 for GM-CFC and 0.017 for BFU-E. The karyotypes of chromosome abnormalities obtained from the colonies in the exposed group were mostly translocations, but deletion and marker chromosomes were also observed. In two individuals, such karyotypic abnormalities as observed in the peripheral lymphocytes were also seen in the myeloid progenitor cells. This finding suggests that atomic bomb irradiation produced a chromosome aberration on multipotent hemopoietic stem cells common to myeloid and lymphoid lineages. These stem cells, although carrying chromosome defects, are likely to have survived for more than 30 years, continuously producing progenitor cells capable of normal-looking growth and differentiation.

Adult↗
PubMed1987

Dysmegakaryocytopoiesis in acute leukaemias: its predominance in myelomonocytic (M4) leukaemia and implication for poor response to chemotherapy.

Megakaryocytopoiesis was morphologically investigated in 129 adults with de novo acute leukaemia. Three types were identified: type I (84 cases), no detectable megakaryocytes; type II (32 cases), quantitatively preserved megakaryocytes with normal morphology; type III (13 cases); quantitatively preserved megakaryocytes but with distinct dysplastic changes such as micromegakaryocytes and megakaryocytes with multiple small separated nuclei. Type III was found in M1 (one out of 21 cases), M2 (one out of 20 cases). M4 (eight out of 24 cases), M6 (two out of four cases) and hypoplastic leukaemia (one out of 13 cases). M3 cases were all classified into type I. Most of acute lymphoid leukaemia cases (21 cases) belonged to type II. Among AML cases, the complete remission (CR) rate by intensive chemotherapy with daunorubicin and cytosine arabinoside was significantly lower in type III (11%) than in types I (87%) and II (71%). Among M4 cases, CR rates in type III (14%) was also significantly lower than those in type I (75%) and II (100%). Thus, the present study indicates the importance of recognizing dysmegakaryocytopoiesis in AML for clarification of the heterogeneous biology or pathophysiology of acute leukaemias and formulation of an appropriate therapeutic strategy.

Acute Disease↗
PubMed1987

Cytogenetic and cytochemical studies on progenitor cells of primary acquired sideroblastic anemia (PASA): involvement of multipotent myeloid stem cells in PASA clone and mosaicism with normal clone.

By cytogenetic and cytochemical analyses of individual hematopoietic colonies, we investigated clonality in progenitor compartments of primary acquired sideroblastic anemia (PASA). Two of our four subjects had reduced but countable numbers of CFU-E, BFU-E, and GFU-GM in methylcellulose culture. In one patient with cytogenetic abnormality of 47, XX, +8 in 67% of the bone marrow cells, cytogenetic analysis of individual erythroid bursts and granulocyte/macrophage colonies demonstrated two populations with and without 8 trisomy, the trisomy clone being 38% in BFU-E and 50% in CFU-GM. These findings indicate involvement of multipotent stem cells in PASA clone and mosaicism of two distinct populations in erythroid as well as granulocyte/macrophage progenitor compartments, the abnormal PASA clone and probably the normal clones. In another case with no cytogenetic abnormality, repeated iron staining showed that 31% to 40% of CFU-E and 25% to 54% of BFU-E had erythroblasts with heavy iron deposits. An ultrastructural analysis of 25 individual erythroid bursts revealed that 32% had highly dysplastic erythroblasts with marked ferruginous iron accumulation in the mitochondria. The other 68% and 15 normal bursts from a healthy control did not have noticeable dysplastic changes and iron deposits in the mitochondria. This cytochemical/ultrastructural mosaicism seems to be compatible with the cytogenetic mosaicism. However, whether the BFU-E derived from abnormal PASA clone selectively manifest iron accumulation in the mitochondria or whether the PASA clone itself shows variable degrees of abnormal iron metabolism remains to be determined by simultaneous performance of ultrastructural and cytogenetic analysis for single bursts.

Adult↗
PubMed1987

Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia.

The bone marrow of a patient with acute undifferentiated leukemia developed unique colonies after a 14-day culture in erythropoietin (EPO)-containing methylcellulose. The colonies consisted of 20 to 200 nonhemoglobinized large blast cells. Cytogenetic analysis of single colonies revealed hypotetraploid karyotypes with several marker chromosomes that were identical to those found in directly sampled bone marrow. The concurrently formed erythroid bursts showed only normal karyotypes. No leukemic colony formation was observed in other culture systems with either colony-stimulating activity (CSA) or phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). The leukemic colonies exhibited a complete EPO-dose dependency similar to that of the patient's normal BFU-E. Although cytochemical and immunologic marker studies of the bone marrow cells failed to clarify the cell lineage of the leukemic cells with extraordinarily large cell size, ultrastructural study revealed erythroid differentiation such as siderosome formation in the cytoplasm and ferritin particles in the rhophecytosis invaginations. These findings indicate that the patient had poorly differentiated erythroid leukemia and that some of the clonogenic cells might respond to EPO in vitro. Corresponding to this biological feature, the leukemic cells were markedly decreased in number in response to repeated RBC transfusions, and partial remission was obtained. These observations suggest that erythroid leukemia distinct from erythroleukemia (M6) with a myeloblastic component, can develop as a minor entity of human acute leukemia.

Acute Disease↗
PubMed1986

Prognostic significance of the morphological dysplastic changes in chronic myelogenous leukemia.

Various morphological dysplastic changes were observed in patients with chronic myelogenous leukemia, especially in the acute crisis. To clarify their significance, we divided 45 patients in the acute crisis into two groups by our scoring system, the dysplastic group and the non-dysplastic group. Five of 25 subjects in the non-dysplastic group entered complete remission. None of 20 subjects in the dysplastic group did so, and the mean survival after the onset of acute crisis is significantly shorter in the dysplastic group than in the non-dysplastic group. Some patients in the dysplastic group had obvious dysplastic changes several months before the acute crisis. These findings suggest that acute crises in some cases may occur with or be preceded by the development of dysplastic clones similar to myelodysplastic syndrome; these patients respond poorly to conventional chemotherapy.

Adult↗
PubMed1986

Dual expression of lymphoid/basophil markers on single blast cells transformed from chronic myeloid leukemia.

A 27-yr-old man developed blastic crisis after the chronic phase of Philadelphia chromosome positive chronic myeloid leukemia (CML). The blast cells expressed terminal deoxynucleotidyl transferase (TdT)+/common acute lymphoblastic leukemia antigen (CALLA)+ phenotypes, corresponding to common ALL type. A vincristine plus prednisolone regimen initially suppressed the blastic proliferation, but the blasts soon reappeared as lymphoblasts, and 65% of them possessed basophil-like granules. Immunologic markers were not altered. The blasts were negative for myeloperoxidase, Sudan black B and periodic acid-Schiff reactions, but were positive for toluidine blue (TB) stain and supravital peroxidase (PO) stain using diaminobenzidine (DAB). These blasts were considered to have immature basophil granules. The supravital staining, for TB or PO in combination with fluorescinated-CALLA staining, directly revealed that single blasts expressed both basophil and lymphoid markers. This biphenotypic blast population was found to be a distinct clone from the initial crisis clone by cytogenetic examination. These findings suggest that the CML clone is derived from a multipotent stem cell common to lymphoid and myeloid lineages, or that dual markers may be expressed on transformed lymphoid or basophil clone as the result of differentiation infidelity probably determined by the genetic derangement in acute crisis.

Adult↗