Disease relevance of IARS

• Because human IRS has previously been shown to be the target of antibodies in autoimmune disease, we discuss the role of protein structural features in the development of an autoimmune response to IRS [1].
• The efficacy of a biocompatible, surgically implantable, antimicrobial release system (IARS) as the exclusive antimicrobial therapy of necrotizing external otitis (NEO) was evaluated in six NEO patients [2].
• Preliminary analyses of treatment results and prognostic factors from the first Intergroup Rhabdomyosarcoma Study (IRS I) suggested that alveolar histology and extremity site were among factors associated with an adverse outcome in clinical group I patients whose tumors had been completely resected [3].
• Both of the IRS proteins modulate VPF/VEGF expression in pancreatic cancer cells by different mechanistic pathways [4].
• Additionally, we studied birthweight as a predictor of the clustering of diseases associated with the IRS, defined as any two or more of the following conditions: hypertension, NIDDM or impaired glucose tolerance, dyslipidaemia [5].

Psychiatry related information on IARS

• This study was carried out to examine the effects of immunochemotherapy with IL-2 and IFNalpha, alone and together, in cancer patients on serum DPP IV activity in relation to changes in depressive symptoms and the IRS [6].
• The results suggest that: (i) alpha2-AR density is sensitive to graded differences in stress-induced anxiety; and (ii) psychological stress is accompanied by intertwined responses in the catecholaminergic system, such as alpha2-ARs, and the IRS, such as Th1/Th2-like functions and the production of TNFalpha [7].
• Recently, however, it has been shown that depression and anxiety disorders are accompanied by activation of the inflammatory response system (IRS) [8].
• BACKGROUND: Recently it has been reported that activation of the inflammatory response system (IRS) may play a role in the aging process and in the pathogenesis of the degenerative changes associated with Alzheimer's disease (SDAT) [9].
• However, no research has examined the IRS in somatization disorder [10].

High impact information on IARS

• Receptor-mediated phosphorylation of the IRS proteins is required for the propagation of signals for mitogenesis, glucose transport, and numerous other biological and biochemical events during insulin signaling [11].
• Insulin signal transduction and the IRS proteins [11].
• We make use of the newly defined metropolitan and micropolitan Core-Based Statistical Areas (CBSAs) and a seven-level size typology to tabulate origin-destination-specific migration flow data from both Census 2000 and IRS tax-return administrative records for the period 1995-2000 [12].
• A chimeric peptide, p21-IRS, consisting of the carboxyl terminal domain of p21 conjugated to a pentapeptide (RYIRS) rapidly enters lymphoid cells and activates apoptosis [13].
• PURPOSE: This study was performed to determine the incidence and risk factors involved in the development of a second malignant neoplasm (SMN) after treatment of primary rhabdomyosarcoma (RMS) in patients enrolled onto Intergroup Rhabdomyosarcoma Studies I and II (IRS I and II) [14].

Chemical compound and disease context of IARS

• 3. Portal and peripheral IRS concentrations, however, remained unchanged in eight dogs and five patients with cirrhosis of the liver [15].
• Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS) [16].

Biological context of IARS

• PATIENTS AND METHODS: Flow-cytometric techniques were used to estimate the ploidy of tumor specimens from 34 patients with embryonal rhabdomyosarcoma who were enrolled in the intergroup rhabdomyosarcoma study III (IRS III) from 1985 to 1991 [17].
• Stress-dependent transactivation of ErbB2/ErbB3 receptors triggers a PI3K cascade that induces serine phosphorylation of IRS proteins culminating in insulin resistance [18].
• Transactivation of ErbB2 and ErbB3 by tumor necrosis factor-alpha and anisomycin leads to impaired insulin signaling through serine/threonine phosphorylation of IRS proteins [18].
• Our results suggest that inappropriate activation of the Rheb/mTOR/S6K pathway imposes a negative feedback program to attenuate IRS-dependent processes such as cell survival [19].
• The results of this study indicate that IL-4 stimulates bifurcating signal pathways that can direct mitogenesis via the IRS-signaling proteins and specific gene expression via the IL-4 NAF [20].

Anatomical context of IARS

• While most receptor tyrosine kinases signal by recruiting SH2 proteins directly to phosphorylation sites on their plasma membrane receptor, the insulin receptor phosphorylates intermediary IRS proteins that are distributed between the cytoplasm and a state of loose association with intracellular membranes [21].
• In addition, we found that the IRS/PI 3'-K pathway is, at least in part, responsible for the prevention of apoptosis by IL-4 in normal splenic B cell cultures [22].
• CONCLUSIONS/INTERPRETATION: The affinity of the PH domain for the phospholipids in the plasma membrane seems to influence the receptor-substrate interaction required for IRS tyrosine phosphorylation, indicating that the PH domain and the PTB domain of IRSs cooperatively function in insulin-stimulated tyrosine phosphorylation of these proteins [23].
• Recent data indicate that low-birthweight adults are at a higher risk than their high-birthweight peers of developing ischemic heart disease or a cluster of conditions known as the IRS, which includes dyslipidaemias, hypertension, unfavorable body fat distribution and NIDDM [5].
• RESULTS: Both univariable and multivariable analysis have shown that the COX-2 expression in human tumor epithelial cells was unrelated to overall patient survival and to disease-free survival, irrespectively of the cutoff point for IRS-COX2 [24].

Associations of IARS with chemical compounds

• The best understood mechanism of IRS-protein-mediated signaling is the binding of SH2 domain-containing signaling molecules (such as PI 3'-kinase) by tyrosine phosphorylation sites on IRS proteins [11].
• We conclude that aspirin may enhance insulin sensitivity by protecting IRS proteins from serine phosphorylation catalyzed by multiple kinases [25].
• Our studies of multiple cell types in both mice and humans show the optimal IRS to contain a GGGG motif within the sequence, and the activity to require a phosphorothioate backbone [26].
• Similarly, an alkaline solution of sodium oleate (pH 9.2) stimulated PBS but not IRS [15].
• In this review, we use structural, evolutionary and functional analysis to divide PTB domains into three groups represented by phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like and phosphotyrosine-independent Dab-like PTBs, with the Dab-like PTB domains representing nearly 75% of proteins encoding PTB domains [27].

Analytical, diagnostic and therapeutic context of IARS

• At 10 years, 62%, 61%, and 77% of the patients were alive after treatment on IRS-I, IRS-II, or IRS-III therapeutic protocols, respectively, similar to figures obtained in all IRS patients [28].
• It has recently been shown that the Met receptor interacts with Gab-1, an IRS-like adaptor protein, via the docking site (Y1349VHVNATY1356VNV) known to bind Grb2 and multiple SH2-containing signal transducers [29].
• We have studied the effect of a protein meal on secretin (IRS) concentration in dogs and humans using a radioimmunoassay of improved sensitivity (8 pg/ml) [15].
• Physiological parameters studied were serum insulin, high density lipoprotein cholesterol, triglycerides, systolic blood pressure, body-mass index, subscapular skinfold thickness, and the IRS factor [30].
• IRS II (Invasive reperfusion study II) was a multicentre randomized trial comparing the efficacy of a 2-5-min 30 U anistreplase intravenous injection with a 1,500,000 U 60-min streptokinase (SK) intravenous infusion in acute myocardial infarction [31].

References