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71.
INTRODUCTION: Tissue transglutaminase (tTG) antibodies are currently recognized as a highly sensitive indicator of celiac disease (CD). Although a high concordance rate between tTG antibodies and anti-endomysial antibodies (EMA) has been reported up to a third of known CD patients are positive for only one of these antibodies. AIM: To determine whether in laboratories in which serum samples previously examined for CD serology markers had not been discarded, these samples should be tested for tTG antibodies. METHODS: Fifty-eight stored (frozen at -70) serum samples of patients previously found to be EMA-negative but positive for one or more of the non-EMA markers: antigliadin antibodies (AGA)-IgA, AGA-IgG, antireticulin antibodies, were tested for anti-tTG antibodies (IMMCO Diagnostics). In patients found to be tTG positive, medical charts were reviewed and patients or their physicians contacted. RESULTS: Twelve of fifty-eight (20.7%) samples were found to be anti-tTG positive. These included: group A: 3/3 samples previously positive for AGA-IgA, AGA-IgG, and antireticulin antibodies. Group B: 3/16 samples positive for AGA-IgA and AGA-IgG. Group C: 3/4 samples positive for AGA-IgA and group D: 3/35 samples positive for AGA-IgG. Of the 12 positive patients, 1 was a 2-year-old boy, 5 were lost to follow up, and 7 underwent an intestinal biopsy. In 3 of these 7 patients, the biopsy was compatible with CD; 2 of these 3 patients were from group A and 1 from group B. CONCLUSIONS: In laboratories where stored serum samples are available, EMA-negative samples previously found to be positive for at least 2 other CD markers should be retested for tTG antibodies. 相似文献
72.
Mandana Nikpour Murray B. Urowitz Dominique Ibañez Dafna D. Gladman 《Arthritis care & research》2009,61(9):1152-1158
Objective
Selection of flare as the primary outcome variable in systemic lupus erythematosus (SLE) clinical trials fails to capture patients with persistently active disease (PAD). We sought to elucidate the frequency and determinants of flare and PAD.Methods
Prospectively collected data from the Toronto Lupus Cohort were used to determine the incidence of flare and PAD in 2004 and 2005. Flare was defined as an increase in SLE Disease Activity Index 2000 update (SLEDAI‐2K) score of ≥4 from the previous visit. PAD was defined as a SLEDAI‐2K score of ≥4, excluding serology alone, on ≥2 consecutive visits. Data from 1, 2, and 3 years prior were used to model flare and PAD in 2004. Model properties were tested for prediction of flare and PAD in 2005.Results
One‐third of the patients had ≥1 flare, whereas nearly half experienced PAD in a given year. Nearly 60% of the patients had episodes of flare or PAD per year. At least 25% of patients had PAD without achieving the definition of flare. In the best‐fitting model, predictors of PAD in 2004 were SLEDAI‐2K score at the start of the outcome interval and prior cutaneous or musculoskeletal disease activity. This model gave 79% correct prediction of PAD in 2005. In contrast, flare prediction models performed poorly.Conclusion
Persistent activity is a common disease state in SLE and should be an outcome variable in SLE clinical trials. Our PAD prediction model may aid prognostication and selection of patients for inclusion in clinical trials. 相似文献73.
74.
A single high-affinity binding site for von Willebrand factor in collagen III, identified using synthetic triple-helical peptides 总被引:5,自引:1,他引:4
Lisman T Raynal N Groeneveld D Maddox B Peachey AR Huizinga EG de Groot PG Farndale RW 《Blood》2006,108(12):3753-3756
The essential event in platelet adhesion to the injured blood vessel wall is the binding to subendothelial collagen of plasma von Willebrand factor (VWF), a protein that interacts transiently with platelet glycoprotein Ibalpha (GPIbalpha), slowing circulating platelets to facilitate firm adhesion through collagen receptors, including integrin alpha2beta1 and GpVI. To locate the site in collagen that binds VWF, we synthesized 57 overlapping triple-helical peptides comprising the whole triple-helical domain of collagen III. Peptide no. 23 alone bound VWF, with similar affinity to that of native collagen III. Immobilized peptide no. 23 supported platelet adhesion under static and flow conditions, processes blocked by an antibody that prevents collagen from binding the VWF A3 domain. Truncated and alanine-substituted peptides derived from no. 23 either strongly interacted with both VWF and platelets or lacked both VWF and platelet binding. Thus, we identified the sequence RGQOGVMGF (O is hydroxyproline) as the minimal VWF-binding sequence in collagen III. 相似文献
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76.
Freedman TS Sondermann H Friedland GD Kortemme T Bar-Sagi D Marqusee S Kuriyan J 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(45):16692-16697
The Ras-specific guanine nucleotide-exchange factors Son of sevenless (Sos) and Ras guanine nucleotide-releasing factor 1 (RasGRF1) transduce extracellular stimuli into Ras activation by catalyzing the exchange of Ras-bound GDP for GTP. A truncated form of RasGRF1 containing only the core catalytic Cdc25 domain is sufficient for stimulating Ras nucleotide exchange, whereas the isolated Cdc25 domain of Sos is inactive. At a site distal to the catalytic site, nucleotide-bound Ras binds to Sos, making contacts with the Cdc25 domain and with a Ras exchanger motif (Rem) domain. This allosteric Ras binding stimulates nucleotide exchange by Sos, but the mechanism by which this stimulation occurs has not been defined. We present a crystal structure of the Rem and Cdc25 domains of Sos determined at 2.0-A resolution in the absence of Ras. Differences between this structure and that of Sos bound to two Ras molecules show that allosteric activation of Sos by Ras occurs through a rotation of the Rem domain that is coupled to a rotation of a helical hairpin at the Sos catalytic site. This motion relieves steric occlusion of the catalytic site, allowing substrate Ras binding and nucleotide exchange. A structure of the isolated RasGRF1 Cdc25 domain determined at 2.2-A resolution, combined with computational analyses, suggests that the Cdc25 domain of RasGRF1 is able to maintain an active conformation in isolation because the helical hairpin has strengthened interactions with the Cdc25 domain core. These results indicate that RasGRF1 lacks the allosteric activation switch that is crucial for Sos activity. 相似文献
77.
Psoriasis is often associated with other diseases, substantially adding to the patient's burden of disease. Recent epidemiologic studies have demonstrated an increased cardiovascular morbidity among patients with psoriasis and psoriatic arthritis (PsA), which contributes to their reduced life expectancy. At the meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) adjacent to the International Federation of Psoriasis Associations (IFPA) congress, members discussed the pathogenetic aspects of this association and resulting consequences for the management of patients with psoriasis and PsA. A future research agenda was considered. 相似文献
78.
79.
80.
Brimberg L Benhar I Mascaro-Blanco A Alvarez K Lotan D Winter C Klein J Moses AE Somnier FE Leckman JF Swedo SE Cunningham MW Joel D 《Neuropsychopharmacology》2012,37(9):2076-2087
Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. 相似文献