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101.
102.
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
103.
A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML. 相似文献
104.
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
105.
M B Forman J Goodin B Phelan H Kopelman R Virmani 《Journal of the American College of Cardiology》1984,4(3):640-643
Isolated infarction of the right ventricle is an extremely rare entity. A patient is described with diffuse interstitial lung disease who developed ST segment elevation in inferior and anterior leads on a routine electrocardiogram and at autopsy was found to have an isolated right ventricular infarct involving approximately 70% of the right ventricular circumference without involvement of the left ventricle and septum. This case illustrates that isolated right ventricular infarction in the presence of cor pulmonale and right ventricular hypertrophy can produce an injury current in the limb and precordial leads of the electrocardiogram which mimics that seen in typical transmural infarction of the left ventricle. 相似文献
106.
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
107.
Surface membrane vesicles from mononuclear cells stimulate erythroid stem cells to proliferate in culture 总被引:6,自引:0,他引:6
In order to examine the contribution of cell surface materials to erythroid burst-promoting activity (BPA), we separated media conditioned by a variety of human cell types into pellets and supernatants by centrifugation. When added to serum-restricted cultures of nonadherent human marrow cells, pellets contained about half of the total stimulatory activity. Freeze-fracture electron microscopy of the pellets revealed the presence of unilamellar membrane vesicles ranging from 0.10 to 0.40 microM in diameter. The amount of BPA in culture increased with added vesicle concentration in a saturable fashion. Preparation of leukocyte conditioned medium (LCM) from 125I-wheat germ agglutinin labeled cells and studies comparing the glycoprotein composition of vesicles with that of leukocyte plasma membranes suggest that LCM-derived vesicles are of plasma membrane origin. Moreover, partially purified leukocyte plasma membrane preparations also contained BPA. While disruption of vesicles by freezing/thawing and hypotonic lysis did not alter BPA, heat, trypsin, or pronase treatment removed greater than 65% of BPA, implying that vesicle surface rather than intravesicular molecules express BPA. Results of BPA assays performed in two-layer clots indicated that proximity to target cells is required for vesicle BPA expression. We conclude that membrane vesicles spontaneously shed from cell surfaces may be important regulators of erythroid burst proliferation in vitro. 相似文献
108.
Background
We examined the association of alcohol use disorders (AUD) with adherence to and health-related quality of life (HRQOL) outcomes of antiretroviral treatment (ART) for HIV/AIDS patients.Methods
A cross-sectional multi-site survey was conducted in 468 drug users and 648 non-drug users (age: 35.4 ± 7.0 years; 63.8% male) in 3 epicentres of Vietnam. AUD, ART adherence, and HRQOL were measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C), the self-reported Visual Analogue Scale (VAS), and the World Health Organization Quality of Life instrument (WHOQOL-HIV BREF).Results
35.0% of drug users were hazardous drinkers, compared to 25.9% of non-drug users. 22.3% of drug users engaged in binge drinking, and 25.9% reported suboptimal ART adherence. Adjusting for propensity scores of AUD, patients who had either at-risk or binge drinking behaviour were about twice as likely to be treatment non-adherent as those who did not have AUD. Hazardous drinkers reported small to medium decrements in the Performance, Physical, Social, Spirituality, and Environment quality of life domains. Binge drinkers had a slightly higher score in Social dimension.Conclusion
AUD is prevalent and negatively affecting adherence to and HRQOL outcomes of ART services in injection-driven HIV epidemics. Screening and intervention are recommended for AUD, especially during the stable periods of ART. Other social and psychological interventions might also enhance patients’ responses to and outcomes of ART in Vietnam. 相似文献109.