Interferon gamma: is it a co-player in the pathogenesis of idiopathic nephrotic syndrome

Introduction: Idiopathic nephrotic syndrome (INS), the most common form of NS in childhood, was considered 4 decades ago as a systemic disorder of T cells, mediated through its released cytokines. To date, the exact incriminated cytokine or immunological mediator is not properly defined. Interferon gamma (IFN-γ), a pro-inflammatory cytokine, is thought to have a role in the provocation of the T cell mediated INS relapse, through promotion of T helper1 (Th1) differentiation and suppression of regulatory T cells (Treg). Aim of the study: to evaluate the immunopathogenic role of IFN-γ in children with steroid sensitive idiopathic nephrotic syndrome (SSNS) through monitoring the changes in its levels with disease course. Methods: This study included twenty-five newly diagnosed children with SSINS. They were all given full dose prednisolone, evaluated at initial diagnosis and at full remission as regards the serum level of IFN-γ. Results: Serum levels of IFN-γ were lowermost at time of diagnosis and increased with remission on corticosteroids. Conclusions: this study points to a role for the lower serum IFN-γ at diagnosis, in the immunopathogenesis of INS than at remission and the rise in its serum level might be a marker of remission induction, however this awaits confirmation in larger scale studies. Studies on renal biopsy specimens are needed to determine the exact renal in situ levels and effects of IFN-

Einfluss von rasse, schlachtgewicht und futterniveau auf spezielle fleischleistungseigenschaften beim rind

International audienc

The stylomastoid artery as an anatomical landmark to the facial nerve during parotid surgery: a clinico-anatomic study

BACKGROUND: The identification of the facial nerve can be difficult in a bloody operative field or by an incision that limits exposure; hence anatomical landmarks and adequate operative exposure can aid such identification and preservation. In this clinico-anatomic study, we examined the stylomastoid artery (SMA) and its relation to the facial nerve trunk; the origin of the artery was identified on cadavers and its nature was confirmed histologically. METHODS: The clinical component of the study included prospective reviewing of 100 consecutive routine parotidectomies; while, the anatomical component of the study involved dissecting 50 cadaveric hemifaces. RESULTS: We could consistently identify a supplying vessel, stylomastoid artery, which tends to vary less in position than the facial nerve. Following this vessel, a few millimetres inferiorly and medially, we have gone on to identify the facial nerve trunk, which it supplies, with relative ease. The origin of the stylomastoid artery, in our study, was either from the occipital artery or the posterior auricular artery. CONCLUSION: This anatomical aid, the stylomastoid artery, when supplemented by the other more commonly known anatomical landmarks and intra-operative facial nerve monitoring further reduces the risk of iatrogenic facial nerve damage and operative time

Literature-based discovery of diabetes- and ROS-related targets

Abstract Background Reactive oxygen species (ROS) are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins) collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG) of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/). Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.http://deepblue.lib.umich.edu/bitstream/2027.42/78315/1/1755-8794-3-49.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/2/1755-8794-3-49-S7.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/3/1755-8794-3-49-S10.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/4/1755-8794-3-49-S8.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/5/1755-8794-3-49-S3.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/6/1755-8794-3-49-S1.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/7/1755-8794-3-49-S4.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/8/1755-8794-3-49-S2.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/9/1755-8794-3-49-S12.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/10/1755-8794-3-49-S11.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/11/1755-8794-3-49-S9.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/12/1755-8794-3-49-S5.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/13/1755-8794-3-49-S6.XLShttp://deepblue.lib.umich.edu/bitstream/2027.42/78315/14/1755-8794-3-49.pdfPeer Reviewe

Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs