摘要:

AbstractFever and neutropenia are life‐threatening complications of chemotherapy in children with cancer. Prompt initiation of empiric broad‐coverage antimicrobial therapy at the first signs of fever has reduced the mortality rates to about 2‐5%. However, myelosuppression with febrile neutropenia is the major dose‐limiting side effect of anticancer chemotherapy, results in prolonged hospitalization, and frequently delays the scheduled cycles of chemotherapy. Prophylactic use of hematopoietic growth factors has been shown to reduce the incidence of fever and infectious complications in children with cancer and neutropenia. Therapeutic use of recombinant human granulocyte‐macrophage colony‐stimulating factor (rHuGM‐CSF) in combination with antibiotics in children with febrile neutropenia has also shown a clear beneficial effect. The number of hospital days due to treatment of febrile neutropenia, the number of days on broad‐spectrum antibiotics and the duration of neutropenia were significantly reduced with the use of rHuGM‐CSF. Importantly, rHuGM‐CSF did not prolong the days with fever in children admitted with febrile neutropenia. In the treatment of documented fungal superinfection, it may be beneficial if rHuGM‐CSF and an antifungal drug are used as combination therapy. rHuGM‐CSF is nontoxic and well tolerated

ISSN:1066-5099    

DOI:10.1002/stem.5530130302

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractCytokines are essential components of our defense and repair systems but also potentially harmful mediators of infectious and immunoinflammatory reactions. Clinically important cytokines function systemically as pleiotropic hormones with overlapping effects on many cell types. All engage in a complex network of agonists and antagonists. Some immunoglobulin G (IgG) antibodies have been found to be potent and specific regulators of cytokines. These antibodies bind interleukin (IL‐1)α, IL‐6, IL‐10, leukemia inhibitory factor (LIF), and interferon (IFN)‐α/β with exceptional force. They neutralize their corresponding cytokines ex vivo and perhaps in vivo, although they may also function as cytokine carriers. The biological role of autoantibodies to cytokines is not yet understood, but they may provide a level of regulation not appreciated at present. Inappropriate production/function of such antibodies could be pathogenetically involved in immunoinflammatory and other diseases. Cytokine antibodies may also contribute to the anti‐inflammatory effects of human

ISSN:1066-5099    

DOI:10.1002/stem.5530130303

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThis review focuses on the roles of transcription factors in hematopoietic lineage commitment. A brief introduction to lineage commitment and asymmetric cell division is followed by a discussion of several methods used to identify transcription factors important in specifying hematopoietic cell types. Next is presented a discussion of the use of embryonic stem cells in the analysis of hematopoietic gene expression and the use of targeted gene disruption to analyze the role of transcription factors in hematopoiesis. Finally, the status of our current knowledge concerning the roles of transcription factors in the commitment to erythroid, myeloid and lymphoid cell types is summarized.

ISSN:1066-5099    

DOI:10.1002/stem.5530130304

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe life span of mature T cells is reviewed. Peripheral T lymphocytes are a heterogeneous population and comprise a mixture of naive, effector and memory cells. The recirculating pool of mature T cells is formed during young life through gradual release of naive T cells from the thymus. In adults, the pool of mature T cells is relatively self‐sufficient, and input of new T cells from the thymus declines to low levels. Studies on T cell turnover indicate that most peripheral T cells can remain in a resting state for long periods (months in rodents and years in humans). Examination of the phenotype of dividing versus nondividing cells suggests that typical naive T cells are long‐lived resting cells whereas the majority of effector and memory T cells have a much more rapid turnover. However, some memory T cells appear to divide very infrequently and eventually return to a resting state. The factors controlling the generation and maintenance of memory T cells are discus

ISSN:1066-5099    

DOI:10.1002/stem.5530130305

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe integrins are a family of adhesion receptors involved in many physiological functions. These molecules are characterized by an ability to dynamically regulate their ligand binding affinity. Several integrins become “activated” or achieve the high affinity state in response to extracellular agonists or signals. High affinity ligand binding does not result from an increase in receptor number or from changes in the receptor microenvironment. Rather, evidence suggests these altered affinity states result from the varied conformations of these molecules. Understanding how these conformational changes are achieved remains an area of great interest in the field. In this review, we will discuss several means and potential mechanisms of integrin activation. First, we will focus on “activators” such as antibodies, peptides, and cations. For the most part, these agents can be viewed as nonphysiological activators that directly effect integrin conformational changes. Later we will discuss how conformational changes are achieved in a physiological sense. Many physiological activators stimulate signal transduction pathways inside the cell and are believed to transmit these signals outward to effect conformational changes. An understanding of integrin activation mechanisms is important as it might suggest ways to regulate cell adhesion in pathology and

ISSN:1066-5099    

DOI:10.1002/stem.5530130306

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractIt is generally assumed that neurogenesis in the central nervous system ceases before or soon after birth. In the last three decades, however, several studies have reported that new neurons continue to be added into the brain of adult fish, frogs, reptiles, birds and mammals. The precursor cells that give rise to the neurons generated in adulthood are generally located in the walls of the brain ventricles. From these proliferative regions, neuronal precursors migrate toward their final targets where they differentiate; they often traverse long distances through complex brain parenchyma. The identity of the neuronal precursors in the brains of adult animals is still unknown. Experiments in adult birds suggest that proliferating radial cells may be the neuronal precursors. In adult mice, cells present in the sub‐ventricular zone can generate neurons in vivo and in vitro. These neuronal precursors can be induced to proliferate in vitro when exposed to growth factors and retain their potential to differentiate into neurons and glia. Whether these putative neural stem cells can differentiate into multiple neuronal types remains to be determined. The neuronal precursors of the adult brain could be used as a source of cells for neuronal transplantation. In addition, these cells could be manipulated in vivo or in vitro to introduce genes into the brain. Adult neurogenesis offers new experimental opportunities to study neuronal birth, migration and differentiation and for the treatment of neurological disease

ISSN:1066-5099    

DOI:10.1002/stem.5530130307

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractCD34+cells were enriched, using a panning method, from peripheral blood (PB) and bone marrow (BM) of healthy volunteers and of patients treated with chemotherapy plus granulocyte colony‐stimulating factor (G‐CSF). In healthy volunteers, PB CD34+cells expressed CD33 and CD13 at a higher frequency than BM CD34+cells, and PB CD34+cells contained a greater number of burst‐forming units‐erythroid (BFU‐E) than colony‐forming units granulocyte‐macrophage (CFU‐GM). Administration of G‐CSF to healthy volunteers induced a marked increase in the number of PB CD34+cells, although the proportions of those expressing CD33, CD13, and c‐kitamong these cells as well as colony‐forming ability were not changed before and after G‐CSF administration. There were no significant differences in surface antigens on PB CD34+cells between healthy volunteers and patients after chemotherapy plus G‐CSF, except for low expression of c‐kitin the PB of patients. However, PB CD34+cells from patients contained almost the same number of CFU‐GM as BFU‐E. These results indicate that there were clear differences in the features of CD34+cells from BM and from PB, and between healthy volunteers and patients after chemotherapy plus G‐CSF. Enriched CD34+cells are useful for analyzing the characteristics of hematopoietic progenitor cells, and such analysis may predict the usefulness of autologous or allogeneic periphera

ISSN:1066-5099    

DOI:10.1002/stem.5530130308

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractHuman umbilical cord blood (UCB) cells are currently considered as a potential source of stem cells for transplantation. However, it remains unclear whether a single collection of UCB contains enough progenitors to allow a successful engraftment in adult patients. We were interested in the comparison of the frequency of primitive progenitors in UCB and in human bone marrow (BM). UCB and BM CD34+cells were purified and compared for their coexpression of CD38, CD33 and HLA‐DR. UCB and BM mononuclear fractions were enriched in CD34+cells using the CEPRATE™ LC system (CellPro, Bothell, WA). Double‐labeling analysis with a flow cytometer showed that 67.9 ± 7.2% of UCB CD34+cells are CD38–, while in BM only 10.9 ± 4.9% of CD34+are CD38–(p<0.001). Moreover, our study indicated that a significantly higher percentage of UCB CD34+is CD33–(97.1 ± 1.2%) compared to BM (61.8 ± 8.6%) (p= 0.013). The coexpression of CD34 with HLA‐DR was not significantly different in UCB and in BM (respectively, 86.3 ± 2.7% and 92.7 ± 5.1%). On the other hand, in vitro assays showed that the number of multipotent (colony‐forming units granulocyte‐erythroid‐macrophage‐megakaryocyte [CFU‐GEMM]), myeloid (colony‐forming units granulocyte‐macrophage [CFU‐GM]) and erythroid (burst‐forming units‐erythroid [BFU‐E]) progenitors is lower in the CD34+population from UCB than from BM. In conclusion, in UCB, we have found a significantly higher percentage of CD34+cells which lacked the expression of CD38 and CD33 antigens suggesting that UCB contains higher proportions of immature progenitor cells (CD34+CD38–and CD34+CD33–) than BM. It seems thus likely that fewer UCB CD34+cells than BM CD34+cells would be required for su

ISSN:1066-5099    

DOI:10.1002/stem.5530130309

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractWe evaluated granulocyte colony‐stimulating factor (G‐CSF) as an adjunct to courses of conventional chemotherapy in 16 children with cancer. One course followed by G‐CSF (20 episodes) was compared to identical courses without G‐CSF (20 episodes) in the same patients. The mean duration of G‐CSF therapy was 8.8 (5‐13) days. The periods of neutropenia (4.8 days versus 16.5 days;p<0.0001), days of hospitalization for febrile neutropenia (13 days versus 65 days;p= 0.02) and days on broad‐spectrum antibiotics (13 days versus 95 days;p= 0.003) were significantly reduced. With the use of G‐CSF the profound neutropenia could be prevented in 11 (55%) episodes. There were two episodes of fever and neutropenia in the G‐CSF group as compared to 10 febrile neutropenias in the control group (p= 0.04). G‐CSF was well tolerated and did not cause additional expenses when compared to the expenses needed for the treatment of febrile neutropenias. The cost benefit analyses showed that through using G‐CSF a savings was realized in the amount of U.S. $20,650 for 20 cycles of chemotherapy, i.e., U.S. $1,033/chemotherapy cycle. We conclude that the use of G‐CSF was efficacious and did not increase the

ISSN:1066-5099    

DOI:10.1002/stem.5530130310

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractChronic exposure of humans to benzene (BZ) causes acute myelogenous leukemia. These studies determined whether BZ, or its reactive metabolite, hydroquinone (HQ), affect differentiation of myeloblasts. BZ or HQ administered to C57BL/6J mice specifically induced terminal granulocytic differentiation of myeloblasts. The ability of the compounds to induce differentiation of the myeloblast was tested directly using the murine interleukin 3 (IL‐3)‐dependent myeloblasts cell line, 32D.3 (G) and the human HL‐60 promyelocytic leukemic cell line. Treatment of HL‐60 myeloblasts with BZ activated protein kinase C and upregulated the 5‐lipoxygenase (LPO) pathway for the production of leukotriene D4(LTD4), an essential effector of granulocytic differentiation. Differentiation was prevented by sphinganine, a kinase C inhibitor, as well as by LPO inhibitors and LTD4receptor antagonists. BZ and HQ also induced differentiation in 32D.3 (G) myeloblasts. Both compounds interact with cellular signaling pathways activated by granulocyte colony‐stimulating factor (G‐CSF) and thus replace the requirement for G‐CSF. IL‐3 induces a growth response, whereas G‐CSF provides both growth and differentiation signals. BZ does not induce growth in the absence of IL‐3, but provides a differentiation signal. Both HQ and LTD4induce differentiation and synergize with IL‐3 for growth, however, neither support growth in the absence of IL‐3. BZ‐induced 32D cells showed a gradual progression of progenitor differentiation to granulocytes similar to that seen with G‐CSF or LTD4. HQ blocks differentiation at the myelocyte stage; only a small percentage of progenitors proceed to granulocytes. BZ, like G‐CSF, upregulates LTD4production, whereas HQ obviates the requirement for LTD

ISSN:1066-5099    

DOI:10.1002/stem.5530130311

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY