ISSN:1066-5099    

DOI:10.1002/stem.5530110616

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractInterleukin (IL)‐ll is a bone marrow fibroblast derived cytokine with a wide spectrum of in vitro biological activities in the hematopoietic, lymphopoietic, hepatic, adipose, neuronal and osteo‐clast systems, either alone or in synergy with other hematopoietic growth factors. In vivo administration of IL‐11 in mice, rats and nonhuman primates has demonstrated the thrombopoietic effects of this cytokine. The expression of the human IL‐11 gene, which is localized at 19q 133‐13.4, can be controlled at both the transcriptional and post‐transcriptional levels. Initial biochemical characterization has identified a 151 kD protein as the potential IL‐11 binding subunit of the receptor complex. Like other cytokines such as IL‐6, leukemia inhibitory factor (LIF), oncostatin M (ONC) and ciliary neurotrophic factor (CNTF), IL‐11 has been shown to utilize IL‐6 signal transducer, gpl30. Because of the overlapping biological activities, the similarities in the predicted tertiary structures, and the sharing of common signal transducer protein, we have compared the signal transduction pathways mediated by these cytokines in various cell types. Studies of protein tyrosine phosphorylation, primary response gene expression and signaling molecules known to be important in transducing mitogenic signals have suggested that there are convergent and divergent points along the signal transduction pathways utilized by IL‐11, IL‐6, LIF and ONC. These observations may explain the biological pleiotropy and redundancy of

ISSN:1066-5099    

DOI:10.1002/stem.5530110617

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractFrom sexual maturity to old age, the mammalian immune system undergoes progressive changes,someof which may predispose individuals to infectious, neoplastic and degenerative diseases. These age‐associated changes are prominent in the T lymphocyte compartment and encompass both the CD4+and CD8+T cell sub‐populations. In this review, we focus on the mouse model system and summarize current information on the existence of functionally distinct subsets within each of the CD4+and CD8+cell subpopu‐lations. We describe how the representation of these subsets is altered during the aging process, with consequent changes in the lymphokine production repertoires and other functional attributes of the T cell pool. Lastly, we present evidence showing that similar changes occur in aging humans and discuss the potential impact of these changes on immune responsiveness in late

ISSN:1066-5099    

DOI:10.1002/stem.5530110618

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractMegakaryocytopoiesis is the cellular developmental process prior to the release of platelets into the circulation. Regulation of megakaryocytopoiesis is a complex phenomenon that begins with commitment of hematopoietic stem cells to the replication and maturation of progenitor cells through endomitosis and megakaryocyte differentiation [1‐4]. Platelet production is determined by the number and size of megakaryocytes in the marrow and may be regulated at two levels: at early stages of cell proliferation resulting in increased megakaryocyte numbers, and at later stages by endoreplication which increases DNA content and the size of megakaryocytes [5].The mature megakaryocyte is a large poly‐ploid cell with a highly defined invaginated membrane (demarcation membrane) and contains the membrane molecules necessary for platelet function [6‐9]. Platelet shedding appears to occur by fragmentation of the cytoplasm of the megakaryocyte. Platelet release is thought to occur via transendothelial processes projecting into the vascular compartment [10,11], although several studies indicate that megakaryocytes lodged in the lungs are capable of platelet formation [12‐17]. The factors stimulating megakaryocytopoiesis in the lung have not been well characterized.In the past, the study of megakaryocyte development in vivo and in vitro was hampered by the rarity of megakaryocytes in the bone marrow, the poorly defined cell populations, and inadequate assays. These prior studies of megakaryocyte development have been discussed in the recent past byR. Hoffman[1],N. Williams[3], andM. W. Long[2]. An attempt will be made in this review to highlight and synthesize various new concepts of regulation of megakaryocyto

ISSN:1066-5099    

DOI:10.1002/stem.5530110619

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530110620

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe EORTC Preclinical Therapeutic Models Group (PTMG), formerly known as the Clonogenic Assay Screening Study Group (CASSG), began experiments in 1982 to investigate the feasibility of doing collaborative studies using in vitro clonogenic assays. The human colon adenocarci‐noma cell line WiDr was selected as the model with which all participating laboratories would work. During the course of these studies, representatives from 34 different institutions located in 10 European countries participated. The first two collaborative experiments attempted to standardize the assay techniques using a double layer agar clonogenic assay. The results indicated that it was not possible to truly standardize these techniques in an international setting. The overall results demonstrated that the WiDr cell line grew well under a variety of conditions and that cloning efficiencies were independent of cell concentration, provided that a concentration of about 3,000 cells/ml was not exceeded. For the next series of protocols, the overall objectives were modified so that each laboratory could use its preferred assay technique whereas the WiDr cells were standardized by being expanded in a single center and sent to participants as viable cells. Analysis of the pooled results indicated that there was steady improvement in repro‐ducibility for the group as a whole with repetition of the protocol. Drug dose responses with doxorubicin and etoposide showed good reproducibility from experiment to experiment The results with cisplatin suggested that the sensitivity of this cell line may be affected by the presence of reduced sulfhydryl in some tissue culture media. The overall experienc

ISSN:1066-5099    

DOI:10.1002/stem.5530110621

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

ISSN:1066-5099    

DOI:10.1002/stem.5530110622

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractAbstract. CD34'DR ‐ and CD34‘DR’ cells were isolated from the marrow mononuclear cells of five patients with chronic myelogenous leukemia (CML) carrying the Philadelphia (Ph) chromo ‐ some. Analysis of bcr/abl hybrid mRNA in indi ‐ vidual colonies from a single cell using reverse transcriptase polymerase chain reaction (RT‐PCR) demonstrated the presence o r absence of the hybrid mRNA. For patient 1 in the chronic phase of CML, the hybrid mRNA was detected in all colonies derived from CD34+DR+ and CD34'DR ‐ hemopoietic progenitors. In contrast, for patient 2 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34+DR+ progenitors but not in any from CD34+DR ‐ prog ‐ enitors. For patient 3 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34‘DR’ but in only some of the colonies from CD34'DR ‐ progenitors. For patients 4 and 5 in the acute crisis of CML, the mRNA was found in a portion of colonies from CD34+DR+ and CD34'DR ‐ progenitors. These results indicated that normal clones can persist in CD34'DR ‐ prog ‐ enitors in some patients with CML, even when chromosome analysis detects the Ph chromosome in all me

ISSN:1066-5099    

DOI:10.1002/stem.5530110623

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe present multicenter study was undertaken to confirm whether filgrastim/recombinant human granulocyte colony stimulating factor (rhG‐CSF) could mobilize residual multipotential stem cells by its Go‐shortening effect in patients with aplastic anemia (AA) and induce a multilineage response. Twenty‐seven patients with acquired severe or moderate AA received long‐term administration (2 to 12+ months) of rhG‐CSF in doses from 100 to 400 ug/body/day by s.c. injection or 250 to 1,500 m̈g/body/day by i.v. infusion. Twenty‐six out of the 27 evaluable patients showed a substantial increase in neutrophils associated with a recovery of myeloid precursors in bone marrow within one month of therapy. Interestingly, 10 out of the 27 patients showed a dramatic improvement in severe anemia after two to ten months of therapy. Moreover, severe thrombocytopenia improved after two to four months of therapy in three out of these ten patients accompanied by a significant increase in megakaryocytes in bone marrow. Clonal cultures of bone marrow cells revealed a recoveryinmyeloid as well as erythroid precursors in most of these ten patients. In two patients who showed a trilineage response, mixed and megakaryocyte colony formations also recovered. These results suggest that long‐term administration of rhG‐CSF mobilizes myeloid, erythroid, megakaryocyte and multipotential progenitor cells and induces a multilineage response in some

ISSN:1066-5099    

DOI:10.1002/stem.5530110624

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractWe examined the effects of interleukin 3 (IL‐3),kitligand and erythropoietin (EPO) on the survival and growth of early appearing spleen colony forming units (CFU‐S8) and late appearing CFU‐S (CFU‐S12) in short‐term liquid culture (SLC). In the control cultures, without any additive, CFU‐S8and CFU‐S,2declined; nearly 10% of the initial number of CFU‐S still survived by the second day of culture. The addition of IL‐3 orkit.‐ligand increased the survival both of CFU‐S, and CFU‐S12,with an increased dose of concentration, at final concentrations of 10‐200 U/ml and 500‐50 dilution, respectively. However, only the survival of CFU‐S, increased when EPO was added up to 10 U/ml, while the frequency of CFU‐S12was not higher than in the control culture. The percentage of CFU‐S8and CFU‐S12in DNA synthesis, evaluated in3H‐TdR cytocide experiments, increased after one day in culture with each of the three factors. The results suggest that all three factors stimulated the proliferation of both populations of CFU‐S, but the two populations showed different patterns of response to each factor; EPO stimulates the proliferation of CFU‐S12that differentiate into CFU‐S8that have less capacity for self‐renewal, while the addition of IL‐3 orkit‐ligandcauses an increase in the number of both populations due to the stimulation of an earlier stage of stem cell differentiation or self‐renewal of CFU‐S12. Our experimental system (SLC‐CFU‐S assay) is useful for evaluating the response of hematopoietic stem cells to cytokines which promo

ISSN:1066-5099    

DOI:10.1002/stem.5530110625

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY