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1. |
Cell differentiation in acute myeloid leukemia |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 1-16
Inge Olsson,
Gösta Bergh,
Mats Ehinger,
Urban Gullberg,
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摘要:
Abstract:Acute myeloid leukemia (AML) is characterized by a differentiation block leading to accumulation of immature cells. Chromosomal translocations in AML affect transcription factors that are involved in regulation of myeloid differentiation. Aberrant expression of these factors interferes with differentiation events and has a role in the pathogenesis of AML through superactivation or (dominant negative) repression of genes regulating proliferation and differentiation or by interference with assembly of the transcription complex for these genes. The maturation arrest can be reversed by certain agents as judged by results from investigations of myeloid leukemic cell lines and from treatment of acute promyelocytic leukemia (APL) patients with all‐transretinoic acid. Inactivation of the p53 and retinoblastoma (Rb) tumor suppressor genes is also associated with the pathogenesis of leukemia through effects on the cell cycle, and manipulation of these genes can affect differentiation of AML cells. With differentiation therapy, when successful as in APL, the leukemic cell mass is reduced to allow restoration of normal hematopoiesis and clinical remission, but the disease is not cured. However, initial reduction of the cell mass by maturation can increase the probability for cure with chemotherapy. Overexpression of suppressor genes may increase the probability for differentiation. Most probably, particular molecular defects of subgroups of AML have to be explored to find optimal strategies for treatment including both blocking the cell cycle, promoting terminal differentiation, and inducing apoptosis as well as strengthening the immune respons
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00483.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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2. |
Monoclonal antibody‐based methods for quantitation of hemoglobins: application to evaluating patients with sickle cell anemia treated with hydroxyurea |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 17-24
Nava Epstein,
Michael Epstein,
Arielle Boulet,
Eitan Fibach,
Griffin P. Rodgers,
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摘要:
Abstract:High‐titer monoclonal antibodies (mAb) were raised against chromatographically purified human hemoglobin (Hb) species.These mAb were specific for either Hb A, Hb F, Hb S or Hb C. Based on these antibodies, which were directly conjugated with either fluorochromes or an enzyme (horseradish peroxidase), we developed immunoassays for determining the Hb profile in the peripheral blood; an enzyme‐linked immunosorbent assay (ELISA) for determining the absolute and relative quantities of various Hb species and one‐step immunolabeling for fluorescence microscopic and flow cytometric analyses of the distribution of RBC with respect to their Hb types. We utilized these methods for monitoring the Hb F level and the percentage of Hb F‐containing cells in patients with sickle cell anemia undergoing treatment with hydr
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00484.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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3. |
Little evidence for clonal evolution of malignant haematopoietic cells following relapse after autologous bone marrow transplantation |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 25-32
Hanne Jørgensen,
Peter Hokland,
Arne Willy Jensen,
Marianne Hokland,
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摘要:
Abstract:By screening for immunoglobulin (Ig) and T‐cell receptor (TCR) gene rearrangements in bone marrow samples aspirated at different time points during the course of disease from 43 patients with acute leukaemia we have analysed the extent of clonal evolution after autologous bone marrow transplantation (ABMT) and addressed the issue of whether the Southern Blot method has the power to reveal clonal proliferations representing minimal residual disease (MRD) in the autologous bone marrow grafts. Our results show that no clonal proliferations were detectable in any of the 43 bone marrow grafts analysed, even after we analysed DNA preparations in 5 cases from cells highly enriched for cells of the original malignant immunophenotype. Moreover, as judged by the Ig‐ and TCR gene configurations in 11 patients, relapse arose from the original clone even though minor clonal variations did occur in about half of the relapsing patients. We conclude that while the Southern Blot method can detect gene receptor rearrangements in the majority of patients with acute leukaemias and high‐grade non‐Hodgkins lymphomas, it is not useful for predicting relapse after ABMT. On the other hand, it is possible – by employing it – to evaluate whether or not relapse after ABMT arises from the original malignant clone and to what extent clonal evolution has
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00485.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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4. |
In vivobiological response following low‐dose interleukin‐2 in complete remission B‐cell non‐Hodgkin's lymphoma patients |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 33-37
Angela Vecchi,
Luigi Cavanna,
Paolo Avanzini,
Vincenzo Callea,
Andrea Velardi,
Nicola Albi,
Pierluigi Tartoni,
Laura Bensi,
Paola Valentini,
Rosina Longo,
Stefano Sacchi,
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摘要:
Abstract:The aim of the present study is to verify whether recombinant interleukin‐2 (rIL‐2) at low doses is well tolerated in aggressive lymphoma in complete remission (CR), and if there may be a biological justification for its use as a remission‐maintenance therapy able to reduce the percentage of relapses. We treated 6 patients with B‐cell non‐Hodgkin's lymphoma (B‐NHL) in CR following PM‐Cytabom with rIL‐2 3 IMU s.c. x 5 d per wk, every other wk for 8 wk. Our results show that this treatment provokes statistically significant changes in the absolute number of lymphocytes, eosinophils, CD25+ and CD122+ cells and soluble IL‐2 receptors; these doses, however, are not sufficient to modify CD3+, CD16+ and CD56+ cell values or natural killer and lymphokine activated killer cell activity. Thus these findings do not appear to constitute a biological rationale for the use of rIL‐2 at this dose and schedule as a remission‐maintenance therapy in B‐cell NHL. Nevertheless, the results are a valid basis for further study of the use of the same rIL‐2 doses for a longer period of time in combination with other cytokines, in the hope that the biological effects can be augmented without increasi
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00486.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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5. |
Deficiency of P‐selectin in a patient with grey platelet syndrome |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 38-41
Alexey V. Mazurov,
Dimitry V. Vinogradov,
Svetlana G. Khaspekova,
Anatoly V. Krushinsky,
Ludmila V. Gerdeva,
Sergei A. Vasiliev,
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摘要:
Abstract:Patient B.G. is a 29‐yr‐old female with a lifelong bleeding disorder characterized clinically by a highly increased bleeding time, menorrhagias, long‐lasting bleeding after cuts and tooth extractions and large post‐traumatic haematomas. Her coagulation tests were within normal range, platelet count was 140,000–160,000 per μl, but platelet function was impaired as demonstrated by the absence of collagen‐induced aggregation, although no abnormalities were detected in aggregation response to ADP and ristocetin. Morphologically her platelets were characterized by gigantic size – average profile area was about 2.5 times higher than that of control donors, and severe deficiency of α‐granules – only 16% of their number in control donors. These features taken together indicated the diagnosis of grey platelet syndrome. As has been shown by quantitative immunoblotting, patient's platelets contained small amounts of α‐granule membrane protein P‐selectin – about 15% of that in control donors. The content of plasma membrane glycoproteins IIb–IIIa and Ib was not reduced, suggesting the specific deficiency of α‐granule membrane protein. Thus, B.G. is the second patient described in the literature (see also Lageset al, J Clin Invest1991: 87: 919–929) with combined defici
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00487.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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6. |
Intensive remission induction therapy for chronic myeloid leukemia in blast phase with a goal of post‐remission bone marrow transplant →— a pilot study |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 42-45
J. H. Lipton,
H. A. Messner,
J. E. Curtis,
H. L. Atkins,
M. D. Minden,
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摘要:
Abstract:An intensive protocol utilizing mitoxantrone, high‐dose cytarabine, vincristine, etoposide and methylprednisolone as induction therapy for chronic myeloid leukemia in blast transformation is described. Fourteen patients were treated, with a remission/second chronic phase achieved in 64%. None of the 3 patients older than 50 yr responded. Complete hematological responses were seen in 9 of the 11 younger patients, 4 of whom also became BCR‐ABL negative by Southern Blot analysis. Four patients went on to allogeneic bone marrow transplant. Median remission durations were 4.5 (1–5) and 8.5 (5–16) months in the non‐transplanted and transplanted cohorts, respectively. Median survival is 1.5 (0.5–3), 9.5 (7–14) and 17 (14–61 +) months in the non‐responding, responding non‐transplanted and transplanted cohorts, respectively. Toxicity, particularly gastrointestinal, was significant. This represents an aggressive protocol that should be reserved for patients who are potential tr
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00488.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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7. |
Functional abnormalities in granulocytes predict susceptibility to bacterial infections in chronic lymphocytic leukaemia |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 46-53
M. Itälä,
O. Vainio,
K. Remes,
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摘要:
Abstract:Leukocyte functions were studied in 22 patients with chronic lymphocytic leukaemia (CLL) and were related to the patients' susceptibility to infections. In CLL patients with a history of infections, compared with CLL patients without infections or healthy controls, there were significant impairments of most granulocyte functions; random migration, N‐formyl‐methionylleucylphenylalanine (fMLP) and C5a stimulated chemotaxis and chemiluminescence response were decreased. No differences in these functions between CLL patients without infections and healthy controls were observed. Phagocytosis and intracellular killing of granulocytes were intact in all patients with CLL. By univariate analysis, neutrophil count and serum IgG level also predicted susceptibility to infections. By multivariate analyses, granulocyte chemotaxis and chemiluminescence remained as statistically significant predictors of infections. The lymphocyte functions (mitogen‐induced lymphocyte proliferation and immunoglobulin productionin vitro) were equally impaired in all patients with CLL and differed significantly from the respective functions in healthy control subjects. We conclude that impairments in granulocyte functions contribute to susceptibility to infections i
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00489.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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8. |
Investigation of microcytosis: a comprehensive approach |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 54-61
Sara Mach‐Pascual,
Regis Darbellay,
Pierre‐Antonio Pilotto,
Photis Beris,
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摘要:
Abstract:Microcytosis is a highly prevalent finding during blood examination. This study investigates the causes of microcytosis (defined as mean corpuscular volume (MCV)<82 fl) in 466 patients referred to our laboratory for suspected hemoglobinopathy. The following data were obtained: Hb, MCV, serum iron, transferrin, ferritin, HbA2, HbF, isoelectric focusing of the Hb, gene mapping of chromosome 16 with Xba I and Bgl II and hybridization with an α‐ and a ζ‐probe, inflammatory status. Results show that iron deficiency remains the first cause of microcytosis (35.2% of our patients), even in a selected population such as ours. Deletional α‐thalassemia, probably the most frequent hemoglobinopathy throughout the world, represents the second most frequent cause of microcytosis (31.1%), followed by β‐thalassemia heterozygous state (18.9%). Of our patients, 1.3% had microcytosis due to the presence of an abnormal hemoglobin (HbC, Hb S/C, HbE). Three cases (0.6%) had other possible causes of microcytosis. Of the remaining 60 cases, 28 had an inflammatory state. Finally, 32 cases (6.9%) remain unexplained; taking into consideration the origin of these cases, their hematological parameters and their family history, we postulate that these cases are at high risk for non‐deletional
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00490.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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9. |
Spouses of demented patients with low cobalamin levels: a new risk group for cobalamin deficiency |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 62-67
R. Carmel,
K. Cairo,
W. Bondareff,
P. S. Gott,
J. L. Cummings,
V. W. Henderson,
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摘要:
Abstract:Low serum cobalamin levels are common in conditions such as dementia and often represent mild deficiency. We surveyed serum cobalamin levels prospectively in spouses and blood relatives of demented patients to determine if any familial predisposition exists for the low levels. Cobalamin status in most of the relatives found to have low levels was assessed further by means of blood counts, metabolic tests, neurologic evaluation, absorption studies and response to cobalamin therapy. Serum cobalamin levels in 36 spouses correlated with those of the 36 demented patients related to them (r= 0.46,p= 0.004). A significant association was not seen in 34 blood relatives of 34 demented patients (r= 0.27). Most importantly, 67% of the spouses of demented patients with low serum cobalamin had low values themselves, compared with only 3% of the spouses of patients with normal levels (p= 0.001). Detailed study of 4 of the 5 spouses (and 3 blood relatives) with low cobalamin levels showed no anemia in any case. Nevertheless, 4 of the subjects had metabolic evidence of deficiency and one had electrophysiological abnormalities; all these defects improved with cobalamin therapy. These observations identify a hitherto unsuspected group of people at high risk for cobalamin deficiency and suggest that spouses of demented patients with low cobalamin levels should also have their cobalamin levels measured. The increased frequency of low serum cobalamin levels in spouses of demented patients with low levels represents in most cases a true, mild cobalamin deficiency that responds to treatment.
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00491.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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10. |
Serum thrombopoietin and plasma glycocalicin concentrations as useful diagnostic markers in thrombocytopenic disorders |
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European Journal of Haematology,
Volume 57,
Issue 1,
1996,
Page 68-71
S. Kunishima,
T. Tahara,
T. Kato,
S. Kobayashi,
H. Saito,
T. Naoe,
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摘要:
Abstract:Using enzyme‐linked immunosorbent assays, we measured the concentrations of serum thrombopoietin (TPO) and plasma glycocalicin, a proteolytic fragment of platelet glycoprotein Ibα, in 13 patients with myelodysplastic syndrome (MDS), aplastic anaemia (AA) or idiopathic thrombocytopenic purpura (ITP). In the patients with AA or MDS, the TPO concentrations were remarkably increased, and their glycocalicin concentrations were decreased compared with the normal control individuals. In the patients with ITP, however, the TPO and glycocalicin levels were not changed as much as in the AA/MDS patients in spite of the same degree of thrombocytopenia. During immunosuppressive treatment of ITP patients, there was an inverse relationship between the level of TPO and the platelet count. Thus, measurements of TPO and glycocalicin levels are useful for the diagnosis of thrombocytopenia, and our results from ITP patients did not support the model which suggested the simple feedback regulation of TPO in thrombocytopen
ISSN:0902-4441
DOI:10.1111/j.1600-0609.1996.tb00492.x
出版商:Blackwell Publishing Ltd
年代:1996
数据来源: WILEY
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