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51.
Transforming growth factor beta (TGF-beta) is a potent and selective growth inhibitor of early hematopoietic progenitors and leukemic cells. The cellular mechanism(s) underlying this antiproliferative effect is, however, currently unknown. In the present study, we demonstrate that TGF-beta inhibits the expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), and granulocyte-CSF (G-CSF) receptors on murine factor-dependent and independent hematopoietic progenitor cell lines without a significant change in receptor affinity. A maximum reduction in GM-CSF receptor numbers of 65% to 77% was observed by 96-hour incubation with TGF-beta. The TGF- beta induced trans-down-modulation of GM-CSF receptors was prolonged, noncytotoxic but reversible, and not due to endogenous production of GM- CSF. The TGF-beta induced reduction in CSF receptor numbers preceded TGF-beta's growth inhibitory action. In addition, the ED50 (1 to 10 pmol/L) for TGF-beta's CSF receptor modulatory and antiproliferative effect was similar. The effect of TGF-beta on cell surface CSF receptor expression was specific, because the expression of other cell surface proteins (Ly 5 and Ly 17) was not affected by TGF-beta treatment, and because other growth inhibitors (tumor necrosis factor and interferon) did not affect CSF receptor expression. These data suggest that the downregulation of the growth of hematopoietic progenitor cells by TGF- beta involves reducing the cell surface expression on growth factor receptors. 相似文献
52.
Weisdorf DJ; Verfaillie CM; Davies SM; Filipovich AH; Wagner JE Jr; Miller JS; Burroughs J; Ramsay NK; Kersey JH; McGlave PB 《Blood》1995,85(12):3452-3456
Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
53.
Mona Jabbour MD Martin H Osmond MD CM Terry P Klassen MD MSc 《Annals of emergency medicine》1996,28(6):690-698
Study objective: To determine the effectiveness of life support courses for health care providers on the basis of one of three outcomes: (1) patient mortality and morbidity, (2) retention of knowledge or skills, and (3) change in practice behavior. Methods: English-language articles from 1975 to 1992 were identified through MEDLINE and ERIC searches, bibliographies of articles, and current abstracts. Studies were considered relevant if they included a study population of life support providers, an intervention of any of the identified life support courses, and assessment of at least one of the three listed outcomes. Relevant studies were selected and validity scores were assigned to them by agreement of two independent reviewers, using a structured form to assess validity. Data on setting, methods, participants, intervention, and outcomes were then abstracted and verified. Results: Seventeen of 67 identified studies pertaining to life support courses met the inclusion criteria. (1) All three mortality and morbidity studies indicated a positive impact, with an overall odds ratio of .28 (95% confidence interval [CI], .22 to .37). (2) No net increase in scores was found in 5 of 8 studies of retention of knowledge and in 8 of 9 studies of skills retention. Two of three studies reporting refresher activities yielded positive effects on knowledge retention. Outcomes were not significantly different between groups taught with modular or didactic techniques. (3) Studies assessing behavioral outcome were methodologically weak. Conclusion: Among providers, retention of knowledge and skills acquired by participation in support courses is poor. However, refresher activities increase knowledge retention. Modular courses are as good as lectures for learning course material. There is evidence that use of the Advanced Trauma Life Support course has decreased mortality and morbidity. Further studies of patient outcome and provider behaviors are warranted. [Jabbour M, Osmond MH, Klassen TP: Life support courses: Are they effective? Ann Emerg Med December 1996;28:690-698.] 相似文献
54.
Carlos O. Weiss MD Ravi Varadhan PhD Milo A. Puhan MD PhD Andrew Vickers PhD Karen Bandeen-Roche PhD MS Cynthia M. Boyd MD MPH David M. Kent MD CM MSc 《Journal of general internal medicine》2014,29(4):653-660
Most people with a chronic disease actually have more than one, a condition known as multimorbidity. Despite this, the evidence base to prevent adverse disease outcomes has taken a disease-specific approach. Drawing on a conference, Improving Guidelines for Multimorbid Patients, the goal of this paper is to identify challenges to the generation of evidence to support the care of people with multimorbidity and to make recommendations for improvement. We identified three broad categories of challenges: 1) challenges to defining and measuring multimorbidity; 2) challenges related to the effects of multimorbidity on study design, implementation and analysis; and 3) challenges inherent in studying heterogeneity of treatment effects in patients with differing comorbid conditions. We propose a set of recommendations for consideration by investigators and others (reviewers, editors, funding agencies, policymaking organizations) involved in the creation of evidence for this common type of person that address each of these challenges. The recommendations reflect a general approach that emphasizes broader inclusion (recruitment and retention) of patients with multimorbidity, coupled with more rigorous efforts to measure comorbidity and comorbidity burden and the influence of multimorbidity on outcomes and the effects of therapy. More rigorous examination of heterogeneity of treatment effects requires careful attention to prioritizing the most important comorbid-related questions, and also requires studies that provide greater statistical power than conventional trials have provided. Relatively modest changes in the orientation of current research along these lines can be helpful in pointing to and partially addressing selected knowledge gaps. However, producing a robust evidence base to support patient-centered decision making in complex individuals with multimorbidity, exposed to many different combinations of potentially interacting factors that can modify the risks and benefits of therapies, is likely to require a clinical research enterprise fundamentally restructured to be more fully integrated with routine clinical practice. 相似文献
55.
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57.
Genetic and non‐genetic factors that increase the risk of non‐syndromic cleft lip and/or palate development 下载免费PDF全文
58.
The midwifery art has emphasised the uniqueness of human beings throughout its Nordic history. The educated Nordic midwife has in the last decade celebrated several hundred years of memories. This article studies how the key ideas of the midwifery art and patterns of ideas become evident in the zeitgeist from the beginning of the 19th century to the millennium in the Nordic countries. The legacy and pattern of ideas of the art of midwifery are interpreted in relation to the texts of the selected historical sources and based on Ricoeur's phenomenological-hermeneutic approach to the text and further to the dedication of understanding and interpretation. The historical sources refer to unprinted primary sources from historical archives and printed secondary and tertiary sources. The patterns of ideas include a tripartite whole: the true cultivation of the head, the philosophy and aesthetics of the hand, the strength of the heart and the drive of calling. These ideas open for unique visions and attest to the evident in modern midwives. Today's midwives have academic training with examinations, and the education is based on scientific evidence. The midwife profession is authorised by the state and supervised by the authorities. 相似文献
59.
60.
C M Gall S H Hendry K B Seroogy E G Jones J W Haycock 《The Journal of comparative neurology》1987,266(3):307-318
Immunoreactivities for gamma-aminobutyric acid (GABA) and the dopamine-synthesizing enzyme tyrosine hydroxylase (TH) were localized ultrastructurally and colocalized at the light microscopic level in neurons of the rat main olfactory bulb. By means of a simultaneous indirect immunofluorescence technique, GABA and TH immunoreactivities were found to coexist in a large number of neurons in the glomerular and external plexiform layers. Virtually all the TH-immunoreactive periglomerular neurons also contained GABA immunoreactivity (GABA-I) while there was an additional number of GABA-immunoreactive periglomerular cells (27%) which did not contain TH immunoreactivity (TH-I). In contrast, the numerous tufted-type neurons in the glomerular and superficial external plexiform layers which contained TH-I did not contain GABA-I. In the external plexiform layer (EPL), 41% of the immunoreactive neurons contained GABA-I alone, 24% contained TH-I alone, and 35% contained both. EPL neurons containing GABA-I only or both GABA-I and TH-I never exhibited tufted cell morphological characteristics and were generally of the short-axon type. Electron microscopic examination of GABA-I and TH-I elements in the glomerular layer detected morphologically similar periglomerular perikarya and intraglomerular processes immunoreactive for each substance and other neurons and processes of the same type containing neither GABA-I or TH-I. These data indicate that the classical neurotransmitters GABA and dopamine coexist in large numbers of neurons in the rat main olfactory bulb including characteristic periglomerular cells and certain other local-circuit neuronal types. 相似文献