223 research outputs found
Peripheral capillary non-perfusion in asymptomatic Waldenström's macroglobulinemia
<p>Abstract</p> <p>Background</p> <p>To report the rare association of peripheral retinal ischemia in a patient with Waldenström's macroglobulinemia.</p> <p>Case Presentation</p> <p>A 39-year old man with a recent diagnosis of asymptomatic Waldenström's macroglobulinemia (WM) was referred from his physician for ocular evaluation. The fundus examination in his right eye (RE) revealed very mild central vein dilation, while retinal hemorrhages associated with microaneurismal alterations of the vascular plexus were detected at the temporal periphery. Fluoroscein angiography of his RE revealed an extended area of capillary dropout distal to the microaneurismal lesions. In our patient with WM an extensive area of capillary non-perfusion, in the absence of severe involvement of the posterior pole was documented; this association to the best of our knowledge has never been reported before.</p> <p>Conclusion</p> <p>Although the incidence of the disease is rare, meticulous examination of the retinal periphery should be performed in all patients with WM and vice versa the differential diagnosis of peripheral retinal ischemia of unknown origin should include an investigation to rule out asymptomatic Waldenström's macroglobulinemia.</p
Autoimmune and autoinflammatory mechanisms in uveitis
The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis
In a randomized trial in Malawi of azithromycin versus placebo in over 2,000 pregnant women, Jim Neilson and colleagues show no benefit of azithromycin for a number of outcomes including preterm birth and prenatal death
Osteoprotegerin in Exosome-Like Vesicles from Human Cultured Tubular Cells and Urine
Urinary exosomes have been proposed as potential diagnostic tools. TNF superfamily cytokines and receptors may be
present in exosomes and are expressed by proximal tubular cells. We have now studied the expression of selected TNF
superfamily proteins in exosome-like vesicles from cultured human proximal tubular cells and human urine and have
identified additional proteins in these vesicles by LC-MS/MS proteomics. Human proximal tubular cells constitutively
released exosome-like vesicles that did not contain the TNF superfamily cytokines TRAIL or TWEAK. However, exosome-like
vesicles contained osteoprotegerin (OPG), a TNF receptor superfamily protein, as assessed by Western blot, ELISA or
selected reaction monitoring by nLC-(QQQ)MS/MS. Twenty-one additional proteins were identified in tubular cell exosomelike
vesicles, including one (vitamin D binding protein) that had not been previously reported in exosome-like vesicles.
Twelve were extracellular matrix proteins, including the basement membrane proteins type IV collagen, nidogen-1, agrin
and fibulin-1. Urine from chronic kidney disease patients contained a higher amount of exosomal protein and exosomal
OPG than urine from healthy volunteers. Specifically OPG was increased in autosomal dominant polycystic kidney disease
urinary exosome-like vesicles and expressed by cystic epithelium in vivo. In conclusion, OPG is present in exosome-like
vesicles secreted by proximal tubular epithelial cells and isolated from Chronic Kidney Disease urine.This work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDINREN RD06/0016, RD12/0021, PI11/01854, PI10/00072 PI09/
00641 and PS09/00447); Comunidad de Madrid (Fibroteam S2010/BMD-2321, S2010/BMD-2378); Sociedad Española de NefrologÍa; European Network (HEALTH
F2-2008-200647); DIALOK European project LSHB-CT-2007-036644; Fundacion Lilly and IRSIN/FRIAT to JE; Programa Intensificación Actividad Investigadora (ISCIII/
Agencia Laín-Entralgo/CM) to AO; Instituto de Salud Carlos III (FIS PI11/01401, CP09/00229); and Fundación Conchita Rábago de Jiménez DÍaz to GAL. The funders
had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip
Diagnostic techniques for inflammatory eye disease: past, present and future: a review
Investigations used to aid diagnosis and prognosticate outcomes in ocular inflammatory disorders are based on techniques that have evolved over the last two centuries have dramatically evolved with the advances in molecular biological and imaging technology. Our improved understanding of basic biological processes of infective drives of innate immunity bridging the engagement of adaptive immunity have formed techniques to tailor and develop assays, and deliver targeted treatment options. Diagnostic techniques are paramount to distinguish infective from non-infective intraocular inflammatory disease, particularly in atypical cases. The advances have enabled our ability to multiplex assay small amount of specimen quantities of intraocular samples including aqueous, vitreous or small tissue samples. Nevertheless to achieve diagnosis, techniques often require a range of assays from traditional hypersensitivity reactions and microbe specific immunoglobulin analysis to modern molecular techniques and cytokine analysis. Such approaches capitalise on the advantages of each technique, thereby improving the sensitivity and specificity of diagnoses. This review article highlights the development of laboratory diagnostic techniques for intraocular inflammatory disorders now readily available to assist in accurate identification of infective agents and appropriation of appropriate therapies as well as formulating patient stratification alongside clinical diagnoses into disease groups for clinical trials
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