Intestinal pseudo-obstruction in patients with systemic sclerosis: an analysis of the Nationwide Inpatient Sample.
2016; 55 (4): 654-658
Colonic plasmacytomas: a rare complication of plasma cell leukemia.
2015; 47: E77-8
Dietary gluten triggers concomitant activation of CD4(+) and CD8(+) alpha beta T cells and gamma delta T cells in celiac disease
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013; 110 (32): 13073-13078
In silico analysis of T-bet activity in peripheral blood mononuclear cells in patients with inflammatory bowel disease (IBD).
In silico biology
2009; 9 (5-6): 355-363
Intestinal pseudo-obstruction is a rare gastrointestinal complication in patients with SSc without large studies examining its prevalence or outcomes. We aimed to compare outcomes in SSc patients with intestinal pseudo-obstruction to patients with intestinal pseudo-obstruction secondary to other causes, and SSc patients without intestinal pseudo-obstruction.This is a case-control study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the period 2002-2011. We included patients with the previously validated International Classification of Diseases-Clinical Modification-9 code 710.1 for SSc in combination with codes for intestinal pseudo-obstruction, and determined length of hospitalization and the risks for surgical procedures, use of total parenteral nutrition (TPN) and in-hospital mortality.A total of 193 610 SSc hospitalizations occurred in the USA between 2002 and 2011, of which 5.4% (n = 10 386) were associated with a concurrent intestinal pseudo-obstruction diagnosis (cases). In-hospital mortality was 7.3%. In multivariate analyses, cases were more likely to die during the inpatient stay and to receive TPN than patients with idiopathic intestinal pseudo-obstruction (control group 1), patients with intestinal pseudo-obstruction and diabetes (control group 2), and SSc patients without intestinal pseudo-obstruction (control group 3). Cases had longer in-hospital stay than control groups 2 and 3, and were less likely to undergo surgical procedures than control groups 1 and 2.Intestinal pseudo-obstruction is a rare cause of hospitalization in patients with SSc, but is associated with high in-hospital mortality in comparison with other SSc patients and those with intestinal pseudo-obstruction secondary to other causes.
View details for DOI 10.1093/rheumatology/kev393
View details for PubMedID 26615031
Separable and redundant regulatory determinants in Cactus mediate its dorsal group dependent degradation
2001; 128 (15): 2963-2974
T-bet (TBX21) is a transcription factor that regulates T-cell differentiation, and has recently been implicated in the pathogenesis of Crohn's disease (CD). The regulatory networks through which T-bet affects immune function are unknown. An NCBI gene expression profile from patients with CD and controls was analyzed. T-bet transcription factor binding sites and promoter modules were identified using promoter analysis software. Functional correlations between T-bet-containing promoters were determined using data mining and ontological analysis. T-bet expression in CD peripheral blood mononuclear cells (PBMCs) (n=59) was significantly reduced compared to control (n=42) (p<0.0001) and ulcerative colitis PBMCs (n=26), (p=0.005). The promoter regions of all genes differentially-expressed in CD were probed for T-bet Transcription Factor Binding Sites (TFBSs). Twenty-three genes contained transcription-factor binding sites for T-bet; 8 were down-regulated, and 15 were up-regulated in CD-PBMCs. Three genes (S100A16, ABHD3 and EZH1) that were down-regulated in CD-PBMCs contained a complex promoter module consisting of T-bet and EGRF transcription-factor binding sites. Ontological analysis revealed that a significant number of differentially-expressed genes that contain T-bet binding sites are involved in innate immunity (8 genes, Z-score 4.11) and signal transduction (5 genes, Z-score 2.65). This combination of gene expression datasets and promoter analysis has identified a network of genes that contain simple T-bet binding sites, and complex T-bet promoter modules, in their promoter regions. These results implicate a mechanism through which T-bet may influence innate immunity in CD.
View details for DOI 10.3233/ISB-2009-0410
View details for PubMedID 22430437
Dorsal-ventral polarity within the Drosophila syncytial blastoderm embryo is determined by the maternally encoded dorsal group signal transduction pathway that regulates nuclear localization of the transcription factor Dorsal. Nuclear uptake of Dorsal, a Rel/NFkappaB homolog, is controlled by the interaction with its cognate IkappaB inhibitor protein Cactus, which is degraded on the ventral side of the embryo in response to dorsal group signaling. Previous studies have suggested that an N-terminally located kinase target motif similar to that found in IkappaB proteins is involved in the spatially controlled degradation of Cactus. We report studies of the in vivo function and distribution of fusion proteins comprising segments of Cactus attached to Escherichia coli beta-galactosidase (lacZ). Full-length Cactus-lacZ expressed in vivo normalizes the ventralized phenotype of embryos that lack Cactus and faithfully reconstitutes dorsal group-regulated degradation, while fusion protein constructs that lack the first 125 amino acids of Cactus escape dorsal group-dependent degradation. Furthermore, Cactus-lacZ constructs that lack only the putative IkappaB-dependent kinase target-like motif can nevertheless undergo spatially regulated dorsal group-dependent degradation and we have identified the regulatory determinant responsible for dorsal group-dependent degradation of Cactus in the absence of this motif. Taken together, our studies indicate the presence of two distinct redundantly acting determinants in the N terminus of Cactus that direct dorsal group-dependent degradation. Strikingly, the regulatory domain of human IkappaBalpha can also direct polarized degradation of Cactus-lacZ fusion protein.
View details for Web of Science ID 000170604900011
View details for PubMedID 11532919