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61.
Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins 总被引:1,自引:0,他引:1
The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF). 相似文献
62.
63.
Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4 总被引:4,自引:0,他引:4
Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci. 相似文献
64.
C B Hu E Y Lee J E Hewitt J U Baenziger J Z Mu K DeSchryver-Kecskemeti D H Alpers 《Gastroenterology》1991,101(6):1477-1487
Because specific uptake of the asialoglycoprotein haptocorrin has been reported in suckling distal intestine, evidence of the asialoglycoprotein receptor in rat ileum was sought. On Western blot, two different polyclonal antisera against purified rat holoreceptor recognized only proteins of the size of the minor receptor components (51 and 55 kilodaltons) in both suckling and adult rat intestine. Messenger RNA encoding the minor component (RHL-2/3) was detected in total RNA extracted from rat ileum. Calcium-specific binding of porcine or rat haptocorrin-[57Co]cobalamin complexes was detected in the brush border membranes of distal suckling rat and porcine small intestine. This binding was almost completely blocked by another asialoglycoprotein, asialofetuin. The pH optimum for binding was 6-9, with a Ka of 0.25 nmol/L and a capacity of 4.6 fmol/mg protein. These properties, with the exception of the low capacity, are all consistent with those of the intact receptor on hepatocytes. The intestinal receptor was localized not to the basolateral membrane, as in the liver, but to the apical brush border, as suggested by the binding data. Furthermore, immunoperoxidase stains of paraffin-embedded tissue detected strong binding to the brush border and apical phagolysosome of mid and distal suckling rat intestine. These data show that, contrary to expectations, the minor components of the asialoglycoprotein receptor are functional and expressed in the apical membrane of the suckling intestine. The abundance of the protein by Western blot suggests possible roles for it in the neonatal gut other than haptocorrin binding. 相似文献
65.
Determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease: The DOC study 下载免费PDF全文
Sarah J. Ronaldson MSc BSc Lisa Dyson MSc BA Laura Clark MSc BSc Catherine E. Hewitt PhD MSc BSc David J. Torgerson PhD MSc Brendan G. Cooper PhD MSc BSc Matt Kearney MPH MB ChB William Laughey MBChB MSc Raghu Raghunath PhD MD Lisa Steele BSc Rebecca Rhodes BMED Sci Joy Adamson PhD MSc BSc 《Journal of evaluation in clinical practice》2018,24(3):487-495
66.
Benjamin W. Dean Sarah N. Hewitt Morgan C. Begos Angela Gomez Locksley L. McV. Messam 《Transfusion and apheresis science》2018,57(1):40-45
Objectives
To estimate the associations of nationality, university program, donation history and gender, with blood donation barriers experienced by non-donating students on the day of a campus blood drive. This project focused particularly on nationality and the effect of the different blood donation cultures in the students' countries of origin.Methods
A retrospective cohort study of 398 North American and Caribbean university students was conducted at St. George's University, Grenada, in 2010. Data were collected from non-donating students on campus while a blood drive was taking place. Log-binomial regression was used to estimate associations between the exposures of interest and donation barriers experienced by the students.Results
North American (voluntary blood donation culture) students were more likely than Caribbean (replacement blood donation culture) students to experience “Lack of Time” (relative risk (RR)?=?1.57; 95% confidence interval (CI): 1.19–2.07) and “Lack of Eligibility” (RR?=?1.55; 95% CI: 1.08–2.22) as barriers to donation. Conversely, Caribbean students were a third as likely to state “Lack of Incentive” (RR?=?0.32; 95% CI: 0.20–0.50), “Fear of Infection” (RR?=?0.35; 95% CI: 0.21–0.58), and “Fear of Needles” (RR?=?0.32; 95% CI: 0.21–0.48) were barriers than North American students.Conclusions
University students from voluntary blood donation cultures are likely to experience different barriers to donation than those from replacement cultures. Knowledge of barriers that students from contrasting blood donation systems face provides valuable information for blood drive promotion in university student populations that contain multiple nationalities. 相似文献67.
Laura Jefferson Karen Bloor Catherine Hewitt 《Journal of the Royal Society of Medicine》2015,108(4):136-141
Objectives
To investigate the effect of physician gender on consultation length in UK hospital outpatient clinics and compare this, through meta-analysis, with previous studies outside the UK.Design
Observational data on clinic times were analysed and findings were combined in a meta-analysis with existing studies investigating the effect of physician gender on consultation length.Setting
UK hospital practice.Participants
A total of 174 observations of outpatient consultations with 10 hospital specialists (consultants) from different specialties in two UK hospital trusts.Main outcome measures
Clinic times were recorded and analysis of consultation length was undertaken with physician gender as a covariate. Data were then synthesised through meta-analysis with 10 existing studies in this field.Results
No statistically significant difference was found in the length of consultations for male and female doctors in these UK hospital settings. When pooled with existing studies, consultations with women doctors were found to be approximately two minutes longer than with men (p = 0.01).Conclusions
Findings from this analysis of clinic consultations in the UK National Health Service do not support previous studies, which were undertaken predominantly in North America and primary care settings. Overall, meta-analysis suggests doctors’ gender may influence consultation length. Gender differences in communication should be considered in training clinicians and in overall clinical practice. 相似文献68.
69.
Objective
The aim of the present study was to determine the risk of myopathy in older people receiving statin therapy.Methods
Eligible studies were identified searching Ovid Medline, EMBASE, Scopus, CINAHL, Cochrane and PSYCHINFO databases (1987 to July 2014). The selection criteria comprised randomized controlled studies that compared the effects of statin monotherapy and placebo on muscle adverse events in the older adult (65+ years). Data were extracted and assessed for validity by the authors. Odds ratios and 95% confidence intervals (CIs) were used to calculate binary outcomes. Evidence from included studies were pooled in a meta-analysis using Revman 5.3.Results
The trials assessed in the systematic review showed little or no evidence of a difference in risks between treatment and placebo groups, with myalgia [odds ratio (OR) 1.03, 95% CI 0.90, 1.17; I2 = 0%; P = 0.66] and combined muscle adverse events (OR 1.03, 95% CI 0.91, 1.18; I2 = 0%; P = 0.61) (myopathy). No evidence was found for an increased risk of rhabdomyolysis (OR 2.93, 95% CI 0.30, 28.18; I2 = 0%; P = 0.35) in the seven trials that reported this. No trials reported mortality due to a muscle-related event. Discontinuations due to an adverse effect were reduced in the treatment group compared with placebo (OR 0.74, 95% CI 0.50, 1.09; I2 = 0%; P = 0.13).Conclusion
The results obtained from the present review suggest that statins are relatively safe, even in older people. There was no evidence to suggest an increased risk of myopathy in older adults receiving statin therapy. There is slightly increased seen with rhabdomyolysis when compared with the general population, although the event is relatively rare. Statins should be prescribed to elderly people who need it, and not withheld, as its myopathy safety profile is tolerable. 相似文献70.