Soluble HLA measurement in saliva and cerebrospinal fluid in Caucasian patients with multiple sclerosis: a preliminary study

BACKGROUND: Measurement of soluble HLA in body fluids has a potential role in assessing disease activity in autoimmune disorders. METHODS: We applied a solid phase, enzyme-linked immunoassay to measure soluble HLA class I (sHLA-I) and class II (sHLA-II) molecules in the saliva and cerebrospinal fluid (CSF) in 13 untreated patients with relapsing-remitting form of multiple sclerosis (MS). For comparison purposes, we also studied saliva from 53 healthy subjects. RESULTS: Saliva from normal controls had detectable sHLA-I levels in 41 of 53 individuals studied, with values ranging from 9–100 ng/ml (mean = 41 ± 2.8 ng/ml). sHLA-I was undetectable in the saliva in 11 of 13 MS patients, and in none of the CSF specimens. In contrast, mean sHLA-II concentration in the saliva of MS patients was significantly increased compared to controls (386 ± 52 unit/ml vs. 222 ± 18.4 unit/ml, t = 8.68, P < 0.005). The mean CSF sHLA-II level (369 ± 16 unit/ml) was equivalent to the mean sHLA-II concentration measured in saliva (mean = 386 ± 52 unit/ml) (P = 0.7). In patients with brain magnetic resonance imaging (MRI) enhancing lesions (n = 5), reflective of more active disease, CSF sHLA-II averaged 356 ± 26 unit/ml compared to 380 ± 51 in saliva. Similarly, in patients with non-enhancing lesions (n = 8), CSF sHLA-II averaged 377 ± 18 unit/ml compared to 390 ± 77 unit/ml in saliva. Thus, the mean sHLA-II concentration in saliva and CSF was essentially equivalent for MS patients with or without enhancing plaques. CONCLUSION: Our data suggest that the measurement of soluble HLA in saliva, specifically sHLA-II, correlates with the level found in the CSF. Therefore, if sHLA correlates with disease activity in MS, as has been proposed, saliva measurements provide a noninvasive correlate of CSF measurement

Antiphospholipid antibodies: Paradigm in transition

OBJECTIVES: This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP. ORGANIZATION: After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed. CONCLUSION: The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology

A Treatment Trial of Acupuncture in IBS Patients

To compare the effects of true and sham acupuncture in relieving symptoms of IBS

Measurement of the ratio of the inclusive 3-jet cross section to the inclusive 2-jet cross section in pp collisions at √s = 7 TeV and first determination of the strong coupling constant in the TeV range

A measurement is presented of the ratio of the inclusive 3-jet cross section to the inclusive 2-jet cross section as a function of the average transverse momentum, ⟨p[subscript T1,2]⟩, of the two leading jets in the event. The data sample was collected during 2011 at a proton–proton centre-of-mass energy of 7 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 5.0 fb[subscript −1]. The strong coupling constant at the scale of the Z boson mass is determined to be α[subscript S](M[subscript Z])=0.1148±0.0014 (exp.)±0.0018 (PDF)±0.0050(theory), by comparing the ratio in the range 0.42<⟨p[subscript T1,2]⟩<1.39 TeV to the predictions of perturbative QCD at next-to-leading order. This is the first determination of α[subscript S](M[subscript Z]) from measurements at momentum scales beyond 0.6 TeV. The predicted ratio depends only indirectly on the evolution of the parton distribution functions of the proton such that this measurement also serves as a test of the evolution of the strong coupling constant. No deviation from the expected behaviour is observed.United States. Department of EnergyNational Science Foundation (U.S.

Measurement of the charge asymmetry in top-quark pair production in proton–proton collisions at √s = 7 TeV

The difference in angular distributions between top quarks and antiquarks, commonly referred to as the charge asymmetry, is measured in pp collisions at the LHC with the CMS experiment. The data sample corresponds to an integrated luminosity of 1.09 fb[superscript −1] at a centre-of-mass energy of 7 TeV. Top-quark pairs are selected in the final state with an electron or muon and four or more jets. At least one jet is identified as originating from b-quark hadronization. The charge asymmetry is measured in two variables, one based on the pseudorapidities (η) of the top quarks and the other on their rapidities (y). The results A[η over C] = −0.017 ± 0.032 (stat.)[+0.025 over −0.036] (syst.) and A[y over C] = −0.013 ± 0.028 (stat.)[+0.029 over −0.031] (syst.) are consistent within uncertainties with the standard-model predictions.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts