Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72178/1/j.1751-553X.2007.01016.x.pd

Regulatory role of CD8(+ )T lymphocytes in bone marrow eosinophilopoiesis

BACKGROUND: There is a growing body of evidence to suggest that CD8(+ )T lymphocytes contribute to local allergen-induced eosinophilic inflammation. Since bone marrow (BM) responses are intricately involved in the induction of airway eosinophilia, we hypothesized that CD8(+ )T lymphocytes, as well as CD4(+ )T lymphocytes, may be involved in this process. METHODS: Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3(+ )T lymphocytes (NJ.1638; CD3(IL-5+ )mice) were bred with gene knockout mice lacking either CD4(+ )T lymphocytes (CD4(-/-)) or CD8(+ )T lymphocytes (CD8(-/-)) to produce CD3(IL-5+ )knockout mice deficient in CD4(+ )T lymphocytes (CD3(IL-5+)/CD4(-/-)) and CD8(+ )T lymphocytes (CD3(IL-5+)/CD8(-/-)), respectively. Secondly, CD3(+), CD4(+ )and CD8(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3(IL-5+), CD3(IL-5+)/CD8(-/- )and CD3(IL-5+)/CD4(-/- )mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments. RESULTS: The number of BM eosinophils was significantly reduced in CD3(IL-5+)/CD8(-/- )mice compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. Serum IL-5 was significantly higher in CD3(IL-5+)/CD4(-/- )mice compared to CD3(IL-5+ )mice but there was no difference in serum IL-5 between CD3(IL-5+)/CD4(-/- )and CD3(IL-5+)/CD8(-/- )mice. Adoptive transfer of CD8(+), but not CD4(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3(IL-5+)/CD8(-/- )mice developed lower numbers of BM eosinophils compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. CONCLUSION: This study shows that CD8(+ )T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice

Results from the Fourth WMO Filter Radiometer Comparison for aerosol optical depth measurements

This study presents the results of the Fourth Filter Radiometer Comparison that was held in Davos, Switzerland, between 28 September and 16 October 2015. Thirty filter radiometers and spectroradiometers from 12 countries participated including reference instruments from global aerosol networks. The absolute differences of all instruments compared to the reference have been based on the World Meteorological Organization (WMO) criterion defined as follows: 95% of the measured data has to be within 0.005±0.001∕m (where m is the air mass). At least 24 out of 29 instruments achieved this goal at both 500 and 865nm, while 12 out of 17 and 13 out of 21 achieved this at 368 and 412nm, respectively. While searching for sources of differences among different instruments, it was found that all individual differences linked to Rayleigh, NO2, ozone, water vapor calculations and related optical depths and air mass calculations were smaller than 0.01 in aerosol optical depth (AOD) at 500 and 865nm. Different cloud-detecting algorithms used have been compared. Ångström exponent calculations showed relatively large differences among different instruments, partly because of the high calculation uncertainty of this parameter in low AOD conditions. The overall low deviations of these AOD results and the high accuracy of reference aerosol network instruments demonstrated a promising framework to achieve homogeneity, compatibility and harmonization among the different spectral AOD networks in the near future

Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus – correlation with proliferation and clinicopathological parameters

p27 is regarded as a cyclin-dependent kinase inhibitor of the G1-to-S cell cycle progression by suppressing the kinase activity of cyclin/cyclin-dependent kinase complex. This study aimed to investigate p27 expression in the normal endometrium and endometrioid adenocarcinoma of the uterine corpus and the correlation of its expression with cell proliferation and clinicopathological parameters. Tissue samples of 127 endometrioid adenocarcinomas and 15 normal endometria were used in the study. Immunohistochemical staining for detecting p27 and Ki-67 was performed by the labelled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. The expression was given as the labelling index, which indicates the percentage of positive nuclei. p27 staining was observed in the nuclei of the glandular cells in the functional layer of the secretory phase endometrium, whereas it was negative in those of the proliferative phase. In endometrioid adenocarcinomas, the labelling index of p27 expression paradoxically increased more significantly in the higher histological grades and was correlated with that of Ki-67. The high level of p27 expression was associated with clinicopathological parameters such as FIGO stage, lymph node metastasis, lymphovascular space involvement and myometrial invasion. High p27 expression was linked to higher grades of endometrioid adenocarcinoma, cell proliferation and some clinical prognostic factors. These results indicate that p27 might be an indicator of poor prognosis

Possible Relationship between Helicobacter pylori Infection and Cap Polyposis of the Colon

The definitive version is available at www.blackwell-synergy.com.ArticleHELICOBACTER. 9(6): 651-656 (2004)journal articl

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

BACKGROUND: The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. METHODS: MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. RESULTS: Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. CONCLUSIONS: This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

Peptide Bβ15-42 Preserves Endothelial Barrier Function in Shock

Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bß15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bß15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bß15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bß15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bß15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bß15-42 is confirmed in Fyn−/− mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bß15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock

Gut Microbiota, Probiotics and Diabetes

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes