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  • 1
    Abstract: Asthma and autoimmune disease susceptibility has been strongly linked to genetic variants in the 17q21 haploblock that alter the expression of ORMDL3; however, the molecular mechanisms by which these variants perturb gene expression and the cell types in which this effect is most prominent are unclear. We found several 17q21 variants overlapped enhancers present mainly in primary immune cell types. CD4+ T cells showed the greatest increase (threefold) in ORMDL3 expression in individuals carrying the asthma-risk alleles, where ORMDL3 negatively regulated interleukin-2 production. The asthma-risk variants rs4065275 and rs12936231 switched CTCF-binding sites in the 17q21 locus, and 4C-Seq assays showed that several distal cis-regulatory elements upstream of the disrupted ZPBP2 CTCF-binding site interacted with the ORMDL3 promoter region in CD4+ T cells exclusively from subjects carrying asthma-risk alleles. Overall, our results suggested that T cells are one of the most prominent cell types affected by 17q21 variants.
    Type of Publication: Journal article published
    PubMed ID: 27848966
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  • 2
    Keywords: PEPTIDES ; CANCER-IMMUNOTHERAPY ; PROTEOMICS ; REPERTOIRE ; SWATH-MASS-SPECTROMETRY ; BINDING PREDICTIONS ; TARGETED ANALYSIS ; MS DATA ; SEARCH ; IDENTIFICATIONS
    Abstract: We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.
    Type of Publication: Journal article published
    PubMed ID: 26154972
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  • 3
    ISSN: 1573-904X
    Keywords: stability ; degradation ; peptidase ; HPLC ; peptide ; glycopeptide ; glycosylation ; serum ; plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The determination of peptide stability in human serum (HS) or plasma constitutes a powerful screening assay for eliminating unstable peptides from further development. Herein we report on the stability in HS of several major histocompatibility complex (MHC)-binding peptides. Some of these peptides are in development for the novel treatment of selected autoimmune disorders such as rheumatoid arthritis and insulin-dependent diabetes. For most of the 1-amino acid peptides studied, the predominant degradation mechanism is exopeptidase-catalyzed cleavage. Peptides that were protected by d-amino acids at both termini were found to be more stable than predicted, based on additivity of single substitutions. In addition, N-acetylglucosamine glycopeptides were significantly stabilized, even when the glycosylation site was several amino acids from the predominant site(s) of cleavage. This indicates that long-range stabilization is possible, and likely due to altered peptide conformation. Finally, the effect of single amino acid substitutions on peptide stability in HS was determined using a model set of poly-Ala peptides which were protected from exopeptidase cleavage, allowing the study of endopeptidase cleavage pathways.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1590-3478
    Keywords: Microemboli ; Transcranial Doppler ; Mechanical heart valves ; Coagulation ; Echocardiography ; Gaseous bubbles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario I soggetti con valvole cardiache artificiali manifestano frequenti segnali microembolici (MES) al Doppler transcranico: scopo dello studio è di valutare tali fenomeni in soggetti con valvole mono-disco e bi-disco. Abbiamo esaminato con monitoraggio bilaterale transcranico 42 pazienti, di cui 15 portatori di valvole mono-disco e 27 di valvole bi-disco. Per ogni soggetto sono stati registrati i parametri coagulativi ed ecocardiografici, ed e stato effettuato esame eco-Doppler dei vasi sopraaortici. Diciotto pazienti su 42 (43%) hanno manifestato MES, di cui 61 % bilaterali, 17% a sinistra e 22% a destra. Non è stata evidenziata alcuna correlazione significativa tra presenza di MES ed èta del paziente, presenza di fibrillazione atriale, valori di (international normalized ratio), dimensioni delle camere cardiache al-l'ecocardiogramma, sede delta valvola. Un solo paziente su 15 (7%) con valvole mono-disco presentava MES, mentre 17 su 27 (63%) con valvole bi-disco presentava tale fenomeno (p=0.0003). I pazienti con valvole bi-disco e MES avevano valvole di impianto più remoto e, solo per le valvole a sede aortica, dimensioni valvolari maggiori.
    Notes: Abstract Microembolic signals (MES) have been described in patients with different types of prosthetic valves. The aim of our study was to compare prevalence of MES in patients with mono-leaflet and bi-leaflet valves, and to correlate them with different clinical and echocardiographic parameters. We evaluated 42 patients, 15 with mono-leaflet and 27 with bi-leaflet valves, with 30-minute bilateral simultaneous transcranial Doppler monitoring for the identification of MES. All patients performed blood testing for international normalized ratio (INR), color-coded duplex of supra-aortic vessels, and echocardiography. Eighteen patients (43%) showed MES; 61% of MES were detected bilaterally, 17% only on the left and 22% only on the right middle cerebral artery (MCA), with no interhemispheric difference. MES did not correlate with patient's age, echocardiographic parameters, INR, presence of atrial fibrillation, or site of valve replacement. One (7%) of the 15 patients with mono-leaflet valves had MES, as opposed to 17 (63%) of the 27 with bi-leaflet valves (p=0.0003). Patients with bileaflet valves and MES had valves of older implantation and, only for aortic valves, larger valve size.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1590-3478
    Keywords: Coma ; Bilateral ophthalmoplegia ; Top of the basilar syndrome ; Thalamic paramedian infarcts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Una oftalmoplegia bilaterale può essere un segno inusuale di ischemia vertebrobasilare. Riportiamo i casi clinici di due pazienti (di 75 e 73 anni rispettivamente) che hanno presentato, con esordio acuto, compromissione dello stato di coscienza, oftalmoplegia bilaterale con ptosi bilaterale e lieve emiparesi destra. In entrambe le pazienti la RM cerebrale dimostrava lesioni ischemiche talamiche bilaterali e nel mesencefalo, l'ECG rivelava la presenza di fibrillazione atriale e lo studio Doppler delle arterie vertebrali a livello extracranico ed intracranico non risultava alterato. Il coinvolgimento ischemico del mesencefalo e delle regioni talamiche paramediane può, quindi, causare oftalmoplegia bilaterale e disturbi dello stato di coscienza. Nei due casi presentati una embolia cardiogena era il meccanismo eziopatogenetico più plausibile, e la prognosi per la paralisi oculare bilaterale è stata cattiva.
    Notes: Abstract Bilateral ophthalmoplegia may be an unusual sign of vertebrobasilar ischemia. We report the cases of two patients (75 and 73 years old), who suddenly developed drowsiness, bilateral ophthalmoplegia with bilateral ptosis and mild right hemiparesis. In both patients, MRI revealed bilateral thalamic and midbrain infarcts, ECG showed the presence of atrial fibrillation and Doppler study of the extracranial and intracranial vertebral arteries found no significant alterations. Ischemia involving the midbrain and thalamic paramedian regions may cause bilateral ophthalmoplegia and consciousness disturbances. In these two cases, the most plausible etiologic mechanism was cardiac embolism, and the prognosis for bilateral ocular palsy was poor.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1590-3478
    Keywords: Cerebral ischemia ; Prognosis ; Electroencephalography ; Infarct size
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Sarebbe estremamente utile avere a disposizione criteri affidabili, sicuri e rapidamente disponibili per predire precocemente la prognosi dell'ictus ischemico. Lo scopo del nostro studio è di valutare il valore prognostico singolo e combinato di alcuni parametri clinici e strumentali, ottenuti nella fase acuta. Lo studio ha coinvolto 351 pazienti consecutivi, entro 48 ore dall'esordio del loro primo ictus ischemico. Abbiamo scelto di prendere in considerazione otto variabili: età, livello iniziale di coscienza, gravità del deficit motorio, pressione arteriosa, glicemia, alterazioni elettrocardiografiche ed elettroencefalografiche, dimensioni dell'infarto alla TC cerebrale. Al giorno 30 sono state misurate la mortalità e la disabilità. Le variabili significativamente correlate con la disabilità sono risultate: gravità del deficit motorio, alterazioni elettroencefalografiche, dimensioni dell'infarto e (in modo meno significativo) il livello dello stato di coscienza e l'iperglicemia. La pressione arteriosa non dimostrava correlazione significativa con la disabilità. L'analisi logistica ha confermato solo la dimensione dell'infarto, la gravità del deficit motorio e le alterazioni elettroencefalografiche come variabili indipendenti. Sono risultate significativamente correlate con la mortalità: la gravità del deficit motorio, la dimensione dell'infarto, le alterazioni elettroencefalografiche ed elettrocardiografiche, il livello di coscienza e l'iperglicemia. L'analisi logistica ha confermato come variabili indipendenti solo le alterazioni elettroencefalografiche ed elettrocardiografiche. Il valore predittivo della gravità del deficit motorio, della dimensione dell'infarto, del livello di coscienza e dell'iperglicemia è già noto. Vi sono, tuttavia, solo alcune variabili indipendenti predittive di morte (alterazioni elettroencefalografiche ed elettrocardiografiche) e disabilità (dimensione dell'infarto, gravità del deficit motorio, alterazioni eletroencefalografiche). La rilevanza delle alterazioni elettroencefalografiche può essere l'espressione del coinvolgimento di fenomeni dinamici, non strutturali come la penombra ischemica e la diaschisi.
    Notes: Abstract Reliable, simple and safe criteria are needed for the early prediction of short-term outcome in patients with acute ischemic stroke. The aim of our study was to evaluate, in terms of their individual and combined power, the prognostic value of a few widely available clinical and instrumental variables obtained during the acute phase. The study involved 351 consecutive patients who were examined within 48 hours of their first ischemic stroke. Eight variables were chosen: age, initial level of consciousness, limb paresis, arterial blood pressure, glycemia, the results of electrocardiography and electroencephalography, and the infarct size revealed by computed tomography. Mortality and disability were evaluated on Day 30, when the variables that significantly correlated with disability were the severity of limb paresis, electroencephalographic abnormalities, infarct size and (less significantly) the level of consciousness and hyperglycemia. There was no statistical correlation with blood pressure. Logistic analysis confirmed only infarct size, the severity of limb paresis and electroencephalographic abnormalities as independent variables. The variables that significantly correlated with early death were the severity of limb paresis, infarct size, electrocardiographic abnormalities, the level of consciousness, electroencephalographic abnormalities and hyperglycemia. More intriguingly, logistic analysis confirmed only the electroencephalographic and electrocardiographic abnormalities as independent variables. The predictive prognostic value of limb paresis, infarct size, the level of consciousness and hyperglycemia is well known, but we would like to stress the fact that only a few independent variables are predictive of early death (electroencephalographic and electrocardiographic abnormalities) and poor recovery (infarct size, the severity of limb paresis, electroencephalographic abnormalities). The prognostic value of electroencephalography may express the potential involvement of dynamic non-structural phenomena, such as penumbra ischemica and diaschisis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1590-3478
    Keywords: Lyme disease ; Borrelia burgdorferi ; myopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Viene riportato il caso di un giovane affetto da malattia di Lyme, con paralisi periferica del settimo nervo cranico, neurite ottica e miopatia a decorso remittente cronico. Viene sottolineata l'utilità della terapia penicillinica.
    Notes: Abstract We describe a case of Lyme disease with a prolonged relapsing-remitting course, in which peripheral facial palsy, optic neuritis and myopathy were associated. After high-dose penicillin therapy the patient completely recovered.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1590-3478
    Keywords: Carotid stenosis ; stroke ; TIA ; carotid endarterectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Recentemente è stata dimostrata l'efficacia della endoarterectomia carotidea (E.C.) in pazienti sintomatici con stenosi carotidea appropriata di grado elevato (70–99%). Dopo una analisi della evoluzione storica della E.C. quale possibile trattamento preventivo dell'ictus ischemico, abbiamo effettuato una revisione critica dei risultati dello studio Nordamericano ed Europeo, con lo scopo di fornire informazioni pratiche per la gestione del paziente cerebrovascolare.
    Notes: Abstract Carotid endarterectomy (CE) has recently been proved to be beneficial in symptomatic patients with severe (70–99%) appropriate carotid stenosis. After discussing the historical evolution of CE as a possible preventive treatment of ischemic stroke, we review the results of North American and European trials in order to give practical information for the management of cerebrovascular patients.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1420-9039
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Solid state phenomena Vol. 10 (Jan. 1991), p. 283-0 
    ISSN: 1662-9779
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Physics
    Type of Medium: Electronic Resource
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