摘要:

Recently, a novel growth factor has been cloned that has growth promoting activities on a wide variety of hematopoietic cell lineages. This factor has been referred to as mast cell growth factor, stem cell factor, or kit ligand, and will be referred to here as steel factor. Steel factor stimulates the growth of cells via its interaction with the c-kitproto-oncogene, which is a tyrosine kinase receptor that is expressed on the surface of a number of different cell types. In addition to its effects on hematopoiesis, this factor also plays a role in the development of melanocytes and germ cells. The discovery of this growth factor provided the final piece of the puzzle to explain the molecular defects associated with several well known genetic mutations in mice, and has opened the door to under-standing the role of this factor in development. Similar genetic defects may exist in humans as well. The aim of this paper is to review the biological structure and activities of this new growth factor, and to discuss its potential applications in clinical medicine.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Thrombopoietin or thrombocytopoiesis-stimulating factor (TSF) is known to be the natural stimulator of megakaryocytopoiesis and, thus, stimulates thrombocytopoiesis. In the past 15 years, new assay technology and sources of the hormone have made possible partial characterization of the molecule and clarification of the biologic role of thrombopoietin. Experiments describing the biology and characterization of TSF are reviewed. In addition, a brief history of the molecule, its biology, and the effects of thrombopoietin on both thrombocytopoiesis and megakaryocytopoiesis are discussed, including the effects of thrombopoietin on platelet counts, platelet sizes, and incorporation of isotopes. In the discussion of thrombopoietin's control of megakaryocytopoiesis there is specific information showing that thrombopoietin stimulates an increase in megakaryocyte size and number, DNA content, endomitosis, and maturation. Thrombopoietin also increases the number of early precursor cells of the megakaryocytic series, that is, small acetylcholinesterase-positive cells. New information is given on the chemistry of thrombopoietin, along with present assays and the relationship of thrombopoietin to interleukin-6. The clinical aspects of thrombopoietin, with detailed descriptions of several disease states in which decreases and excesses of the hormone have been found, are presented. The potential uses of thrombopoietin in clinical medicine are reviewed. In the near future, it appears that successful gene cloning of the hormone will be achieved, which will allow production of large amounts of recombinant thrombopoietin. The pure material will be helpful in clarifying the hormone's mode of action. Thrombopoietin will no doubt prove to be useful in treating patients with various hematologic disorders, such as patients undergoing bone marrow transplantation, chemotherapy, or radiotherapy, and other patients with various types of marrow hypoplasia.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A number of biologically active and biochemically well-characterized cytokines have been shown to have either direct or indirect suppressive activities on the proliferation/differentiation of myeloid stem/progenitor cells. This article is a brief review of the actions of some of these molecules. These molecules include H-subunit ferritin, macrophage inflammatory protein-1α, the interferons-α, -β, and -γ, the tumor necrosis factors-α and -β (lymphotoxin), prostaglandins, E1and E2inhibin, transforming growth factorβ, and lactoferrin. I will also review the actions of other suppressor molecules, including a newly identified 8-kd molecule that has not yet been sequenced and a synthetic pentapeptide. Current information is given on the in vitro actions of these molecules together with their activity in vivo in animal models. Possibilities for their clinical use are discussed.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

In this article, I have attempted to summarize many studies that clearly demonstrate a major role of combinations of growth factors in the development of blood cells. Clearly, the most striking effects are seen on primitive cells that do not reach full proliferative potential when stimulated by single factors. The treatment of patients with combination growth factor therapy has high potential in the areas of chemotherapy and bone marrow transplantation. In these patients, more rapid regeneration of primitive cells will lead to more rapid and effective recovery. Also, combinations of factors are essential for optimal retrovirus-mediated gene transfer in repopulating stem cells for use in gene replacement therapy. Stem cell factor has been shown to protect burst-forming unitserythroid from the toxic effects of zidovudine (AZT). This is an example where combinations of factors may enable patients to continue treatment regimens for extended periods. The side effects resulting from some factors may be overcome using combination therapy. When combinations of factors are given, greatly reduced doses of each factor can produce results similar to those seen with high doses of a single factor.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

As part of an investigative protocol requiring serial liver biopsies in patients with Type I Gaucher's disease who were receiving enzyme replacement therapy, we gave 11 patients a total of 15 infusions of DDAVP (0.3 μg/kg IV) and measured the Simplate bleeding time pre- and postinfusion. All patients were thrombocytopenic (one patient 100–150,000; seven 66–99,000; and three 50–65,000/μl). Nine of 15 infusions resulted in at least a 2-min shortening of the bleeding time; in 6/11 infusions in which the platelet count was >65,000, the bleeding time shortened to ≤10 min, in 1/11 it shortened ≥2 min but not to ≤10 min. In only 2/4 infusions given to patients with platelet counts <65,000 did the bleeding time demonstrate any significant shortening. None of the six liver biopsies performed in the patients whose bleeding time shortened to ≤10 min resulted in any significant bleeding; blood products were not transfused either pre- or postprocedure. These limited data demonstrate that a high percentage of patients with platelet counts of 65–100,000/μl can manifest a significant shortening of bleeding time following a standard infusion of DDAVP, and that in approximately half of these patients the bleeding time will shorten enough to safely allow the performance of a liver biopsy without the need for prophylactic transfusion of blood products.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Interleukin 6 (IL-6) has been demonstrated to possess a variety of biological and immunological functional properties. Recently, Interleukin 6 has been shown to stimulate in vitro fetal hematopoiesis. In the present study, we investigated the effects of 7 days of rhlL-6 on newborn rat in vivo myelopoiesis. Sprague-Dawley newborn rats (<24 h old) were injected (intraperitoneally) daily for 7 days with either rhlL-6 or PBS/BSA. RhIL-6 induced a mild but significant increase in the peripheral neutrophil count on day 1 (P < 0.02), but had no significant sustained effects during the remaining 7 days of administration. Additionally, rhIL-6 had no significant effect on the bone marrow neutrophil proliferative pool, neutrophil storage pool, the liver/spleen neutrophil storage pool and neutrophil proliferative pools. Although rhlL-6 induced a significant increase in the day 1 platelet count (p < 0.03), it failed to induce a sustained significant increase in the platelet count during the remaining 7 days of administration. RhIL-6 also failed to induce any change in the circulating hematocrit during the 7 days of administration. This study suggests that rhlL-6 failed to induce a significant and sustained increase in the peripheral neutrophil count or platelet count during in vivo administration in neonatal rats. Although rhlL-6 may possess additional immunomodulating effects in the newborn, this 7-day study of rhlL-6 failed to demonstrate any induction of neonatal peripheral neutrophilia or modulation of neonatal myeloid proliferation.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We reviewed the linear growth and growth plate morphology in all children with homozygous β thalassemia followed in Toronto, for whom monthly height percentiles were available before, and for a 36-month period after, the initiation of nightly subcutaneous deferoxamine therapy. All patients were <7 years of age when begun on deferoxamine, and had received nightly deferoxamine for a minimum of 36 months. Marked abnormalities of the metaphyseal growth plate were readily observed in the distal ulnar, radial, and tibial metaphyses in 11 of 37 patients in whom a significant decline in mean height percentile was also noted. (In 10 of these 11 patients, height was less than the 15th percentile after 36 months.) These 11 patients had received a significantly greater (p < 0.025) initial and average daily dose of deferoxamine, and had maintained a significantly lower (p < 0.025) mean serum ferritin concentration over the 36 months, than the remainder of the cohort. To determine whether deferoxamine played a causative role in growth failure, growth in patients who began deferoxamine before the age 2 years was compared to that of patients who began after age 5 years, for the period between 2 and 5 years of age. Only patients begun on deferoxamine prior to age 2 years demonstrated a significant (p < 0.01) decline in height percentile by the third year, implicating deferoxamine therapy as the cause of growth failure. We conclude that both the decline in height percentile and the bony changes observed in well-chelated patients are directly related to deferoxamine therapy. They can be observed even in older patients begun on deferoxamine as late as 5 years of age, with significant declines in serum ferritin over a short period of time, and are not confined to those begun in infancy on nightly deferoxamine. These changes may result from a direct toxic effect of deferoxamine. They may, alternatively or in addition, be due to chelation of other trace minerals required for normal growth, although serum levels of several trace elements tested were normal. Serial radiographs of the radii and femurs in thalassemic patients on deferoxamine may demonstrate early metaphyseal changes. Observation of these abnormalities should be followed by reduction of the nightly dose of deferoxamine to the lowest level that results in negative iron balance, and growth velocity should be observed carefully, in parallel with regular follow-up of bone abnormalities.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The nutritional status and dietary intake of children with sickle cell anemia were examined to confirm the presence of deficiencies. Nine children with sickle cell anemia and 19 controls were assessed. Resting energy expenditure was measured with open circuit indirect calorimetry and body composition was estimated from skinfold measurements. Three-day food records were analyzed for protein, zinc, vitamin A. folic acid, and iron content. Serum vitamin A, red blood cell zinc, red blood cell folate, serum folate, serum ferritin, hematocrit, total urine nitrogen, and 24-h urine creatinine levels were measured. The children with sickle cell anemia were leaner, weighed less, and had lower red blood cell zinc levels, lower serum vitamin A levels, lower urine nitrogen levels, and greater resting energy expenditure than controls. Serum and red blood cell folate levels were within normal ranges and similar to controls. The serum ferritin level was higher than controls and higher than normal for age. Dietary intake of energy and protein was more than that of controls, and dietary intake of zinc, vitamin A, folic acid, and iron was similar to that of controls and adequate compared to the Recommended Dietary Allowances. Further studies are needed to explain the physical and biochemical differences seen in children with sickle cell anemia despite dietary intakes that appear to be adequate and similar to those of controls.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

An infant boy with fetal hydantoin syndrome was evaluated for the finding of thrombocytosis. Delayed splenic maturation was identified by a decreased splenic uptake of99mTc sulfur colloid and by an increased number of pitted erythrocytes at 6 months of age. We speculate that the patient's thrombocytosis may be related to delayed maturation of splenic function and conclude that hyposplenism and secondary thrombocytosis may be associated with fetal hydantoin syndrome.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Peripheral blood stem cells (PBSC) were collected by two leukaphereses and cryopreserved in a 3-year-old girl with T-lymphoblastic leukemia; this was after remission was induced by an investigative regimen when she failed to respond to a first-line induction therapy. The patient received marrow-ablative chemotherapy 4.5 months after the diagnosis; this was followed by the infusion of thawed PBSC (203 x 104CFU-GM/kg). The peripheral granulocyte count reached 0.5 x 109/L by day +7 and the platelet count reached 20 x 109/L by day +9. Thereafter, the leukocyte count increased to 38 x 109/L by day + 14, with a gradual decline to normal levels. She has remained in unmaintained, complete remission 47 months after the autograft, with full school activity. This case illustrates the PBSC autograft is useful as an alternative to bone-marrow transplantation in a selected patient population, and extends the application of cure-oriented therapy to refractory childhood leukemia.

ISSN:0192-8562    

出版商:OVID    

年代:1992

数据来源: OVID