|
1. |
Fanconi anemia revisited: Old ideas and new advances |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 142-153
Claudia C. dos Santos,
Hanna Gavish,
Manuel Buchwald,
Preview
|
PDF (998KB)
|
|
摘要:
AbstractAbstract.This review summarizes both historical and more recent data on the clinical, cellular and genetic features of Fanconi anemia (FA), a rare autosomal recessive disorder. FA patients are characterized by pancytopenia, congenital malformations, growth delay and an increased susceptibility to the development of malignancies, particularly acute myelogenous leukemia. FA cells show chromosomal fragility, slow growth and increased sensitivity to DNA crosslinking agents. FA can be caused by defects in any one of at least four genes. Two general hypotheses have been proposed to explain the underlying defect: loss of a DNA repair function or of a step in the defense toward oxygen toxicity. After many attempts to clone the FA genes, the first one, that defective in group C, has been cloned by complementation of the increased sensitivity of FA(C) cells to mitomycin C and diepoxybutane. This gene (FACC) codes for a novel protein and is ubiquitously expressed. Mutations in various FA(C) patients that cause loss of function have been identified. The review concludes by suggesting directions for future research in FA.
ISSN:1066-5099
DOI:10.1002/stem.5530120202
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
2. |
Interleukin 12: A key modulator of immune function |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 154-168
Stanley F. Wolf,
Derek Sieburth,
Joseph Sypek,
Preview
|
PDF (1286KB)
|
|
摘要:
AbstractInterleukin (IL)‐12 was cloned on the basis of its ability to activate natural killer (NK) cells and promote the development of cytolytic T cells. With further understanding of its activities, IL‐12 has emerged as an important cytokine, affecting both immune and hematologic functions. It has been shown to be necessary for the T cell independent induction of interferon (IFN)‐γ, critical for the initial suppression of bacterial and parasitic infection; for the development of a Th1 response, critical for effective host defense against intracellular pathogens; and for the activation of differentiated T lymphocytes of both CD4+and CD8+phenotype. IL‐12 thus functions to activate and to link the innate and acquired immune responses. The therapeutic potential of these activities is suggested by studies in tumor and microbial models. IL‐12 has suppressed tumor growth in all murine models examined. Antimicrobial activity has been demonstrated in bacterial, yeast, parasitic, and viral models of infection. In many of these models, activity has been linked to production of IFN‐γ and, in the parasite model, to development of a Th1 response. In addition to the therapeutic potential associated with IL‐12 activity in these disease models, the understanding of its role in immune development and interaction with other cytokines, particularly antagonists, such as IL‐4 and IL‐10, has clarified and extended our understanding of immune regulation and should lead to significant developments in understanding the progression of AIDS and the development of vaccine adjuvants able to direct
ISSN:1066-5099
DOI:10.1002/stem.5530120203
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
3. |
Interleukin 13 elicits a subset of the activities of its close relative interleukin 4 |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 169-174
Gerard Zurawski,
Jan E. de Vries,
Preview
|
PDF (469KB)
|
|
摘要:
AbstractInterleukin 13 (IL‐13) and interleukin 4 (IL‐4) are two closely related proteins produced by activated T cells. IL‐4 is a well characterized mediator of various aspects of the immune response, including anti‐inflammatory effects on monocytes and macrophages, regulation of B cell function, T cell growth, and regulation of adhesion molecule expression on endothelial cells. IL‐13, a more recently characterized cytokine, appears to exhibit IL‐4‐like activities on monocytes, macrophages and human B cells, but has no effect on T cells. While there is a close parallel between IL‐4 activities on human and mouse cells, IL‐13 activities in these two systems appear to differ substantially with a notable absence of effect on mouse B cells. This review briefly summarizes the current state of knowledge of the interrelated activities of IL‐13 and IL‐4, explores the basis of these effects at the receptor level and attempts to rationalize the existence of these close relatives via differences in their
ISSN:1066-5099
DOI:10.1002/stem.5530120204
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
4. |
Stochastic effects in hemopoiesis |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 175-179
M. Y. Gordon,
T. A. S. Amos,
Preview
|
PDF (402KB)
|
|
摘要:
AbstractStochastic effects underlie all hemopoietic cell responses but can only be observed at the level of one or a very few cells. Here we have considered the relevance of stochastic effects to aspects of hemopoietic cell development.
ISSN:1066-5099
DOI:10.1002/stem.5530120205
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
5. |
Differential sensitivity to cryopreservation of clonogenic progenitor cells and stromal precursors from leukemic and normal bone marrow |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 180-186
H. A. Zaheer,
F. M. Gibson,
M. Bagnara,
E. C. Gordon‐Smith,
T. R. Rutherford,
Preview
|
PDF (516KB)
|
|
摘要:
AbstractThe survival of human leukemic and normal progenitor cells was determined after cryopreservation. Thirteen marrows from patients with acute myeloid leukemia (AML) were studied as fresh and eight as cryopreserved samples. Marrows from five normal donors were studied as both fresh and cryopreserved samples. Although the number of bone marrow mononuclear cells (BMMC) recovered after cryopreservation was always lower than that originally stored, no significant difference was observed between the clonogenic potential of fresh and cryopreserved BMMC from either the leukemic or the normal samples. When grown in long‐term bone marrow culture (LTBMC), the cultures initiated with cryopreserved BMMC failed to form a confluent stroma, and the duration of nonadherent and progenitor cell production was significantly lower than that from fresh samples. However, when these cryopreserved samples were recharged onto preformed irradiated stroma, the duration of the cultures improved significantly. We conclude that it is the bone marrow stromal cells rather than the clonogenic progenitors which are sensitive to the effects of cryopreservation. Thus cryopreservation does not appear to influence the activity of AML progenitor cells. Our results also indicate that frozen marrow can be used for LTBMC experiments if cultured on a preformed stromal laye
ISSN:1066-5099
DOI:10.1002/stem.5530120206
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
6. |
Isolation and identification of two CD34+cell subpopulations from normal human peripheral blood |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 187-197
Georges Herbein,
Philippe Hénon,
Hanna Sovalat,
Eckart Wunder,
Michèle Baerenzung,
Jeanne Bachorz,
Huguette Lewandowski,
Christine Schweitzer,
Georges Herbein,
Carine Schmitt,
André Kirn,
Preview
|
PDF (840KB)
|
|
摘要:
AbstractCirculating CD34+progenitors were separated from normal human peripheral blood on the basis of size and density by counterflow centrifugal elutriation (CCE). The CD34+cells, 0.15% of peripheral blood mononuclear cells, were heterogeneous with respect to their elutriation characteristics, mainly size and density. The least mature CD34+cells, characterized by lack of CD38 antigen, were predominantly found in the small lymphoid cell fraction. In fractions containing larger and denser cells (large lymphocytes, monocytes, and granulocytes), CD38 was increasingly expressed on the CD34+cells, as were lineage commitment markers CD10 (B lymphoid), CD33 (myeloid), CD13 (myelomonocytic) and CD71 (erythroid) antigens. The smaller and less dense CD34+cells expressed CD34 antigen brightly while the larger and denser CD34+cells expressed it dimly. The smaller and less dense CD34+highcells failed to establish colony growth in short‐term culture while the larger and denser CD34+lowcells gave rise to high counts of colony forming units‐granulocyte macrophage (CFU‐GM). Physical separation on the basis of size and density by CCE differentiates between two main classes of steadystate CD34+cells from normal human peripheral blood. The smaller and less dense CD34+highcells correspond to the earliest progenitors that express differentiation markers poorly but CD34 antigen brightly, do not give rise to short‐term colony growth in vitro, and thus represent indirect evidence for pluripotent hematopoietic stem cells (PHSC). The larger and denser CD34+lowcells are the more mature progenitor cells, already committed to myeloid, lymphoid or erythroid differentiation but only dimly expressing CD34 antigen, and these cells were responsible for short‐term colony growth
ISSN:1066-5099
DOI:10.1002/stem.5530120207
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
7. |
Antileukemic activity of phenylalanine methyl ester (PME): A lysosomotropic peptide methyl ester |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 198-204
Craig S. Rosenfeld,
Preview
|
PDF (390KB)
|
|
摘要:
AbstractThe antileukemic activities of the lysosomotropic compounds, such as phenylalanine methyl ester (PME), have received little attention. In this study, a 3‐[4,5‐Dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to investigate the antileukemic activity of PME. Leukemic specimens from untreated patients that contained greater than or equal to 75% blasts were used. Leukemic cells were treated with PME at 37°C and 22°C in concentrations ranging from 0.5 to 50 mM. Normal blood mononuclear cells served as controls. At both 37°C and 22°C, the recovery of normal peripheral blood cells was 28% following incubation with 50 mM PME. At 37°C, 50 mM PME caused greater than one log reduction of leukemic cells in 13/16 acute myelogenous leukemia (AML), 7/9 acute lymphocytic leukemia (ALL), and 8/8 in blast crisis of chronic myelogenous leukemia (CML‐BC) specimens. PME had less activity at 22°C than at 37°C. PME was compared with 100 m̈g/ml 4‐hydroperoxycyclophosphamide (4HC). In contrast to PME, 4HC was associated with a greater than one log reduction of leukemic cells in only 1/13 AML, 1/3 ALL and 0/6 CML‐BC specimens. 4HC activity exceeded PME activity in only one case each of ALL and prolymphocytic leukemia (PLL). In a case of CD34+B cell ALL, synergy of PME and 4HC was demonstrated. These studies indicate 1) PME has antileukemic activity and 2) 4HC has less antil
ISSN:1066-5099
DOI:10.1002/stem.5530120208
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
8. |
T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 205-213
Fabio Benedetti,
Donata de Sabata,
Giuseppe Perona,
Preview
|
PDF (714KB)
|
|
摘要:
AbstractAcquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disease, characterized by isolated thrombocytopenia and the absence of megakaryocytes in bone marrow. Recent studies suggest that this syndrome is due to diverse etiologies. Humoral or cellular mediated suppression has been alternately demonstrated using an in vitro colony assay for megakaryocytic progenitor cells (colony forming units megakaryocyte, [CFU‐meg]). We studied a patient affected by AATP, who was not responsive to conventional therapy, but did respond to antilymphocyte globulin. The immunological characterization of marrow lymphocytes showed a marked increase of T activated suppressor cells (CD8+/DR+). Low density bone marrow mononuclear nonadherent cells (MNAC) from the patient, either in aplastic phase or in remission phase, were plated in plasma clot either directly or after T cell depletion (T‐dep MNACs). Co‐cultures with normal marrow cells were performed using either T lymphocytes from a normal volunteer donor or patient T lymphocytes. In some experiments we added autologous serum instead of fetal calf serum (FCS). In standard conditions, we observed increased colony formation, which was more evident in remission phase and especially significant after T cell depletion. The T lymphocytes from patient marrow did not modify the number of CFU‐meg when co‐cultured with allogeneic cells. These results indicate that an immune‐mediated mechanism could be responsible for this case of AATP, and that the T cell subset CD8+/DR+is capable of exerting suppression on megakaryocyte differentiation. This suppressive effect seems restricted to patient cells, suggesting a specific auto‐
ISSN:1066-5099
DOI:10.1002/stem.5530120209
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
9. |
c‐kitligand combined with GM‐CSF and/or IL‐3 can expand CD34+hematopoietic progenitor subsets for several weeks in vitro |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 214-224
Rita Steen,
Geir E. Tjønnfjord,
Torstein Egeland,
Lars Mørkrid,
Geir E. Tjønnfjord,
Preview
|
PDF (893KB)
|
|
摘要:
AbstractIt might be possible to facilitate engraftment after transplantation of purified hematopoietic progenitor cells if the cells are stimulated ex vivo prior to transplantation. The aim of this study was to analyze the potential ofc‐kitligand (CKL) combined with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and/or interleukin‐3 (IL‐3) to induce proliferation and differentiation of human bone marrow CD34+cells in vitro. Particular attention was paid to the ability to expand populations that could maintain progenitor characteristics, i.e. CD34 expression and generation of colony forming cells (CFC), for a considerable period of time. Purified CD34+cells were cultured in liquid medium for 42 days interrupted by immunophenotyping and CFC assays.In the presence of CKL combined with GM‐CSF and/or IL‐3, the total number of cells expressing CD34 increased significantly for several weeks after an initial decline. Further, CFC were continually recovered in these cultures. Based on the kinetics and the flow cytometry analysis, the expanding populations that continued to express CD34 probably originated from noncommitted, immature CD34+cell subsets. CKL combined with GM‐CSF and/or IL‐3 also induced strong cell proliferation. The majority of the proliferating cells lost CD34 expression and acquired a series of mature myeloid cell surface markers associated with the monocytic, granulocytic and megakaryocytic lineages. These cells probably originated from committed CD34+cell subsets. We conclude that CKL combined with GM‐CSF and/or IL‐3 can stimulate noncommitted, immature as well as committed CD34+cell populations to expand and to differentiate. This property might be useful in a short‐term ex vivo pretransplant stimulation of CD34+cells in an attempt to facilitate rapid and stable engraftment after
ISSN:1066-5099
DOI:10.1002/stem.5530120210
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
10. |
Leukemia and bone marrow microenvironment |
|
STEM CELLS,
Volume 12,
Issue 2,
1994,
Page 225-226
Subhash C. Gulati,
Brian Nath,
Preview
|
PDF (186KB)
|
|
ISSN:1066-5099
DOI:10.1002/stem.5530120211
出版商:John Wiley&Sons, Ltd.
年代:1994
数据来源: WILEY
|
|