Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, Po2 -14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-i, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (Po2 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis. (J. Clin. Invest. 1994. 93:1564-1570
Background The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZB × NZW) F 1 murine lupus model.
BackgroundVolunteer patients (also known as patient partners (PPs)) play a vital role in undergraduate healthcare curricula. They frequently take part in objective structured clinical examinations (OSCE) and rate aspects of students’ performance. However, the inclusion and weighting of PP marks varies, while attitudes and opinions regarding how (and if) they should contribute towards the pass/fail outcome are uncertain.MethodsA prospective observational study was conducted to explore beliefs of PPs regarding inclusion of their scores in a high stakes undergraduate OSCE in a single UK medical school. All PPs delivering components of the local MBChB curriculum were asked to participate in the questionnaire study. Quantitative and qualitative data were analysed using descriptive statistics and framework analysis respectively.ResultsFifty out of 160 (31% response rate) PPs completed the questionnaire; 70% had participated in a final year OSCE. Thirty (60%) felt their marks should be incorporated into a student’s overall score, while 28% were uncertain. The main reasons for inclusion were recognition of the patient perspective (31%) and their ability to assess attitudes and professionalism (27%), while reasons against inclusion included lack of PP qualification/training (18%) and concerns relating to consistency (14%). The majority of PPs were uncertain what proportion of the total mark they should contribute, although many felt that 5-10% of the total score was reasonable. Most respondents (70%) felt that globally low PP scores should not result in an automatic fail and many (62%) acknowledged that prior to mark inclusion, further training was required.ConclusionThese data show that most respondents considered it reasonable to “formalise their expertise” by contributing marks in the overall assessment of students in a high stakes OSCE, although what proportion they believe this should represent was variable. Some expressed concerns that using marks towards progress decisions may alter PP response patterns. It would therefore seem reasonable to compare outcomes (i.e. pass/fail status) using historical data both incorporating and not incorporating PP marks to evaluate the effects of doing so. Further attention to existing PP training programmes is also required in order to provide clear instruction on how to globally rate students to ensure validity and consistency.Electronic supplementary materialThe online version of this article (10.1186/s12909-017-1063-4) contains supplementary material, which is available to authorized users.
DHEA (dehydroepiandrosterone) is a weak androgen with proposed efficacy in the treatment of mild to moderate lupus, and possible beneficial effects on cardiovascular risk and bone mineral density. We hypothesized that treatment with 200 mg a day of Prasterone (DHEA) would improve pre-clinical measures of atherosclerosis: flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD), and circulating apoptotic endothelial cells (CD 146(AnnV +)), as well markers of bone metabolism. Thirteen premenopausal female patients with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
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