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71.
Cytokine production by primary bone marrow megakaryocytes 总被引:4,自引:2,他引:4
Primary human bone marrow megakaryocytes were studied for their ability to express and release cytokines potentially relevant to their proliferation and/or differentiation. The purity of the bone marrow megakaryocytes was assessed by morphologic and immunocytochemical criteria. Unstimulated marrow megakaryocytes constitutively expressed genes for interleukin-1 beta (IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), by the polymerase chain reaction (PCR) and Northern blot analysis. At the protein level, megakaryocytes secreted significant amounts of IL-1 beta (53.6 +/- 3.6 pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/- 4 pg/mL) but not TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta increased the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture supernatants. Transforming growth factor- beta was also able to stimulate IL-6, IL-1 beta, and GM-CSF secretion, but was less potent than stimulation with phorbol-12-myristate-13- acetate (PMA). The secreted cytokines acted additively to maintain and increase the number of colony-forming unit-megakaryocytes colonies (approximately 35%). These studies demonstrate the production of multiple cytokines by isolated human bone marrow megakaryocytes constitutively or stimulated in vitro. The capacity of human megakaryocytes to synthesize several cytokines known to modulate hematopoietic cells supports the concept that there may be an autocrine mechanism operative in the regulation of megakaryocytopoiesis. 相似文献
72.
73.
Madhotra D Fenton JE Makura ZG Charters P Roland NJ 《Irish journal of medical science》2004,173(4):197-199
Background The timing of aggressive airway intervention in adult epiglottitis is controversial.
Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken.
Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis
between March 1988 and December 2000 was undertaken.
Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman
stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom
progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous
therapy.
Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should
probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate
>30 per minute, pCO2 >45mmHg) disease. 相似文献
74.
Hohenthal U Nikoskelainen J Vainionpää R Peltonen R Routamaa M Itälä M Kotilainen P 《Bone marrow transplantation》2001,27(3):295-300
Parainfluenza virus type 3 (PIV3) is associated with a high mortality rate in BMT recipients with lower respiratory tract infections. We describe nine patients with hematological malignancies (five having undergone either allogeneic or autologous stem cell transplantation) identified as having PIV3 infection during a 2-month period in a Hematology Unit. Four patients with infiltrates on chest radiograph received intravenous ribavirin therapy; all survived. The infection was community-acquired in two patients, while nosocomial origin of the disease was evident, or presumed, in the remaining seven. The policy implemented to control the spread of PIV3 was as follows: (1) nasopharyngeal samples for antigen detection were obtained from all patients presenting with respiratory symptoms; (2) all diagnosed (or suspected) PIV3-positive hematological patients were nursed following contact isolation precautions, preferably in the Infectious Diseases Unit; and (3) staff were given further education on hospital hygiene. Our experience shows that it may be possible to avoid mortality for PIV3 lower respiratory tract infection in immunocompromised patients by early commencement of intravenous ribavirin. It is also possible, even without closing the ward, to contain nosocomial spread of PIV3 by implementing systematic nasopharyngeal sampling for rapid diagnostics, and by strict adherence to cohorting and contact isolation precautions. 相似文献
75.
76.
Ca2+ and phospholipid-dependent protein kinase (protein kinase C) activity is not necessarily required for secretion by human neutrophils 总被引:2,自引:0,他引:2
Ca2+-dependent and phospholipid-dependent protein kinase (PKC) is a receptor for and is activated by phorbol esters. This enzyme is reportedly involved in the mechanism of superoxide anion (O2-) production and the release of intracellular granule contents from human neutrophils. As previously reported by others, we found that greater than 75% of the total cellular PKC activity existed in a soluble form in untreated neutrophils and that this activity was enhanced in a dose- dependent manner by phorbol 12-myristate 13-acetate (PMA) and by phorbol 12,13-dibutyrate (PDBu). Furthermore, mezerein, an analogue of PMA that is thought to be a competitive inhibitor, did not activate PKC, and on the contrary, inhibited PMA-stimulated activity in a dose- dependent manner. Pretreatment of intact neutrophils with PMA or PDBu caused the "translocation" of PKC activity to the insoluble cell fraction; PKC translocation was not detected after mezerein stimulation at any of the tested concentrations. Neither did mezerein cause an increase in intracellular Ca2+, as monitored by Quin 2 fluorescence. Both phorbol esters and mezerein stimulated intact neutrophils to generate O2- and release lysosomal enzymes into the extracellular medium. Finally sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated key differences in the patterns of endogenous phosphoproteins of neutrophils stimulated with phorbol as compared with mezerein. We therefore suggest that PKC activation may not be the only pathway required to elicit neutrophil responses. 相似文献
77.
Adverse effects of the transfusion of homologous blood on tumor recurrence and resistance to bacterial infection have been reported previously, but the findings are inconclusive. A retrospective review of patients undergoing orthopedic surgery was conducted, and the rate of the postoperative infectious complications was compared among those receiving homologous blood, autologous blood, both types, or no transfusion support. An overall postoperative infection rate of 6.1 percent was observed: 6.9 percent among persons receiving homologous blood, 5.0 percent among those receiving autologous blood, 11.9 percent among those receiving both homologous and autologous blood, and 4.9 percent among those not receiving transfusions (p = 0.37). Among patients receiving homologous blood, a subset of 15 patients received homologous whole blood and had an infection rate of 20 percent. Significant predictors of postoperative infection included increasing age, spinal surgery, high admission hematocrit, and greater time in surgery. Of factors relating to transfusion, only the use of homologous whole blood was a significant predictor of postoperative infection, which suggests a detrimental effect of homologous plasma. It can be concluded that, in this group of patients undergoing relatively nontraumatic surgery, several variables that are not related to transfusion, as well as the use of homologous whole blood, were significant predictors of postoperative infection. 相似文献
78.
79.
The hematopoietic stem cells of alpha-thalassemic mice 总被引:1,自引:0,他引:1
The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy. 相似文献
80.
Feng J Yan J Michaud S Craddock N Jones IR Cook EH Goldman D Heston LL Peltonen L Delisi LE Sommer SS 《American journal of medical genetics》2001,105(4):369-374
Estrogen and thyroid hormones exert effects on growth, development, and differentiation of the nervous system. Hormone administration can lead to changes in behavior, suggesting that genetic variants of the estrogen receptor alpha (ERalpha) and the thyroid hormone receptor alpha (TRalpha) genes may predispose to psychiatric diseases. To investigate this possibility, regions of likely functional significance (all coding exons and flanking splice junctions) of the ERalpha and TRalpha genes were scanned in patients with schizophrenia (113), along with pilot studies in patients with bipolar illness (BPI), puerperal psychosis, autism, attention-deficit hyperactivity disorder (ADHD), and alcoholism. A total of 1.18 megabases of the ERalpha gene and 1.16 megabases of the TRalpha gene were scanned with Detection of Virtually All Mutations-SSCP (DOVAM-S), a method that detects virtually all mutations. Four missense mutations, seven silent mutations and one deletion were identified in the ERalpha gene, while only four silent mutations were present in the TRalpha gene. Two of the missense mutations in ERalpha are conserved in the six available mammalian and bird species (H6Y, K299R) and a third sequence variant (P146Q) is conserved in mammals, birds, and Xenopus laevis, hinting that these sequence changes will be of functional significance. These changes were found in one patient each with BPI, puerperal psychosis, and alcoholism, respectively. Analysis of the ERalpha and TRalpha genes in 240 subjects reveals that missense changes and splice site variants are uncommon (1.7% and 0%, respectively). Further analyses are necessary to determine if the missense mutations identified in this study are associated with predisposition or outcome for either psychiatric or nonpsychiatric diseases. 相似文献