Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways

Introduction The post-operative period is characterised by increased IL-6 production and clinical features of immune suppression. In vitro anti-inflammatory actions of IL-6 are mediated through suppression of interferon gamma (IFNγ) [1]. The clinical significance of IL-6 in mediating post-operative immune suppression remains unclear. Objectives To evaluate the role of IL-6 pathways in post-operative immune suppression and the reversibility of this phenomenon. Methods Patients over 45 years old undergoing elective surgery involving the gastrointestinal tract and requiring at least an overnight hospital stay were recruited. The primary outcome was hospital-acquired infection. IL-6 and IFNγ levels were assayed using ELISA preoperatively and at 24 and 48 hours. Pooled healthy control peripheral blood mononuclear cells (PBMCs) were cultured in perioperative serum and CD14+HLA-DR (mHLA-DR) geometric mean florescent intensity (MFI) measured in the presence and absence of interferon gamma (IFNγ) and IL-6 neutralising antibody. Data were analysed with non-parametric statistics. Results 119 patients were recruited and 44 (37%) developed a post-operative infection a median of 9 (IQR 5-11) days postoperatively (Figure 1). IL-6 levels increased from baseline to 24 hours postoperatively (P < 0.0001, Figure 1A) but were then unchanged between 24 and 48 hours (P = 0.06, Figure 1B). Postoperative IL-6 levels correlated with the duration of the procedure (P = 0.009). Higher preoperative IL-6 levels were observed in patients with cancer (P = 0.02). IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with the later occurrence of infectious complications. This pattern remained similar after adjustment for baseline characteristics. Healthy donor PBMCs incubated with postoperative serum downregulated mHLA-DR MFI when compared with serum from baseline (n = 8, p = 0.008). Culturing in the presence of IFNγ 250IU (n = 4) prevented this decrease whereas culturing in the presence of IL-6 neutralising antibody 15ng/ml (n = 8) did not. Conclusions IL-6 levels increase following major surgery and are associated with an increased susceptibility to post-operative infections. Serum obtained from post-operative patients induces an immunosuppressive response through an IL-6 independent pathways which is reversible with IFNγ treatment

Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

OBJECTIVE The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. BACKGROUND The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. METHODS Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. RESULTS Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. CONCLUSIONS IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery

Developing trauma-informed teacher education in England

Trauma-informed practice in education is an area of growing interest in England and internationally. Embracing trauma-informed practice in schools requires trauma and related content to be included in teacher education. Over a period of eight years, a short course was developed and incorporated into the teacher preparation programmes at a large university in England. Through methods of teacher educator self-study and autoethnography, we examine the process of the course’s development and identify mechanisms, enablers and barriers to change in the current policy context of teacher education in England. Important factors that supported change were the gradual development, external collaboration, positive outcomes as a warrant and source of motivation, the development of champions and enthusiasts for trauma-informed practice, and departmental leadership support. Barriers to the development were the constraints of prescribed content on initial teacher education courses, prevailing practices in some schools and settings, challenges in adapting material suitably for all education phases, and some beginning teachers’ responses to personally relevant course content. The successful introduction of the short course demonstrates that inclusion of trauma-informed content in initial teacher education is possible even in an unfavourable policy environment

Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways

Introduction The post-operative period is characterised by increased IL-6 production and clinical features of immune suppression. In vitro anti-inflammatory actions of IL-6 are mediated through suppression of interferon gamma (IFNγ) [1]. The clinical significance of IL-6 in mediating post-operative immune suppression remains unclear. Objectives To evaluate the role of IL-6 pathways in post-operative immune suppression and the reversibility of this phenomenon. Methods Patients over 45 years old undergoing elective surgery involving the gastrointestinal tract and requiring at least an overnight hospital stay were recruited. The primary outcome was hospital-acquired infection. IL-6 and IFNγ levels were assayed using ELISA preoperatively and at 24 and 48 hours. Pooled healthy control peripheral blood mononuclear cells (PBMCs) were cultured in perioperative serum and CD14+HLA-DR (mHLA-DR) geometric mean florescent intensity (MFI) measured in the presence and absence of interferon gamma (IFNγ) and IL-6 neutralising antibody. Data were analysed with non-parametric statistics. Results 119 patients were recruited and 44 (37%) developed a post-operative infection a median of 9 (IQR 5-11) days postoperatively (Figure 1). IL-6 levels increased from baseline to 24 hours postoperatively (P < 0.0001, Figure 1A) but were then unchanged between 24 and 48 hours (P = 0.06, Figure 1B). Postoperative IL-6 levels correlated with the duration of the procedure (P = 0.009). Higher preoperative IL-6 levels were observed in patients with cancer (P = 0.02). IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with the later occurrence of infectious complications. This pattern remained similar after adjustment for baseline characteristics. Healthy donor PBMCs incubated with postoperative serum downregulated mHLA-DR MFI when compared with serum from baseline (n = 8, p = 0.008). Culturing in the presence of IFNγ 250IU (n = 4) prevented this decrease whereas culturing in the presence of IL-6 neutralising antibody 15ng/ml (n = 8) did not. Conclusions IL-6 levels increase following major surgery and are associated with an increased susceptibility to post-operative infections. Serum obtained from post-operative patients induces an immunosuppressive response through an IL-6 independent pathways which is reversible with IFNγ treatment

Frequency and distribution of rare electrophoretic mobility variants in a population of human newborns in Ann Arbor, Michigan

We have summarized the frequency and distribution of the rare variants encountered during the screening of 258 815 allele products, the products of 51 different loci, in 3242 predominantly Caucasian (88 %) newborns. Seventy-nine different rare variants, representing 187 occurrences, were identified. Almost 60 % (46 of 79) of the rare variants occurred as singletons while another 20 % were seen in two unrelated individuals. No rare variants were detected at 18 loci while no variants, either rare or polymorphic, were detected at 14 loci. More rare variants were identified at loci that were classified as polymorphic and also at loci where the gene products exist as a monomer. A positive relationship was observed between variant frequency, either classes or copies, and subunit molecular mass.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65173/1/j.1469-1809.1987.tb01065.x.pd

A QUANTITATIVE MAPPING OF ALKALINE PHOSPHATASE IN THE BRAIN OF THE RHESUS MONKEY *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65477/1/j.1471-4159.1966.tb07513.x.pd

Some Like It Fat: Comparative Ultrastructure of the Embryo in Two Demosponges of the Genus Mycale (Order Poecilosclerida) from Antarctica and the Caribbean

0000-0002-7993-1523© 2015 Riesgo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

THE SURFACE FEATURES OF DROSOPHILA EMBRYONIC CELL LINES

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73303/1/j.1440-169X.1977.00345.x.pd

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

Clathrin Is Spindle-Associated but Not Essential for Mitosis

Clathrin is a multimeric protein involved in vesicle coat assembly. Recently clathrin distribution was reported to change during the cell cycle and was found to associate with the mitotic spindle. Here we test whether the recruitment of clathrin to the spindle is indicative of a critical functional contribution to mitosis.Previously a chicken pre-B lymphoma cell line (DKO-R) was developed in which the endogenous clathrin heavy chain alleles were replaced with the human clathrin heavy chain under the control of a tetracycline-regulatable promoter. Receptor-mediated and fluid-phase endocytosis were significantly inhibited in this line following clathrin knockout, and we used this to explore the significance of clathrin heavy chain expression for cell cycle progression. We confirmed using confocal microscopy that clathrin colocalised with tubulin at mitotic spindles. Using a propidium iodide flow cytometric assay we found no statistical difference in the cell cycle distribution of the knockout cells versus the wild-type. Additionally, we showed that the ploidy and the recovery kinetics following cell cycle arrest with nocodazole were unchanged by repressing clathrin heavy chain expression.We conclude that the association of clathrin with the mitotic spindle and the contribution of clathrin to endocytosis are evolutionarily conserved. However we find that the contribution of clathrin to mitosis is less robust and dependent on cellular context. In other cell-lines silencing RNA has been used by others to knockdown clathrin expression resulting in an increase in the mitotic index of the cells. We show an effect on the G2/M phase population of clathrin knockdown in HEK293 cells but show that repressing clathrin expression in the DKO-R cell-line has no effect on the size of this population. Consequently this work highlights the need for a more detailed molecular understanding of the recruitment and function of clathrin at the spindle, since the localisation but not the impact of clathrin on mitosis appears to be robust in plants, mammalian and chicken B-cells