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Abnormal Regulation (abnormal + regulation)
Selected AbstractsThe role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel diseaseIMMUNOLOGY, Issue 2 2008Megan E. Himmel Summary Two related chronic inflammatory diseases, Crohn's disease and ulcerative colitis, are together often referred to as inflammatory bowel disease (IBD). Current treatment options are not curative, and patients face lifelong therapy and debilitation. IBD is thought to be the product of a combination of genetic and environmental factors that result in the abnormal regulation of immune responses. Experimental models have demonstrated that normal CD4+ T-regulatory (Treg) cell responses and commensal bacteria are required for the maintenance of gut immune homeostasis. Recent evidence that CD4+ T cells express Toll-like receptors (TLRs) and respond directly to TLR ligands, suggests that signals from commensal bacteria may directly affect T-cell responses in the gut. In this review, we focus on evidence that defects in Treg cells may underlie IBD in humans. In addition, we discuss evidence that direct signaling via TLRs to T cells can affect IBD and that T-cell-dependent responses to bacterial proteins, such as flagellin, are central to the aetiology of this disease. [source] Heritability of frontal brain function related to action monitoringPSYCHOPHYSIOLOGY, Issue 4 2008Andrey P. Anokhin Abstract Monitoring the correspondence between the intended and actually executed action, a fundamental mechanism of behavioral regulation, is reflected by error-related negativity (ERN), an ERP component generated by the anterior cingulate cortex. This study examined genetic influences on the ERN and other components related to action monitoring (correct negativity, CRN, and error positivity, Pe). A flanker task was administered to adolescent twins (age 12) including 99 monozygotic (MZ) and 175 dizygotic (DZ) pairs. Genetic analysis showed substantial heritability of all three ERP components (40%,60%) and significant genetic correlations between them. This study provides the first evidence for heritable individual differences in the neural substrates of action monitoring and suggests that ERN, CRN, and Pe can potentially serve as endophenotypes for genetic studies of personality traits and psychopathology associated with abnormal regulation of behavior. [source] Lupus-like disease and high interferon levels corresponding to trisomy of the type I interferon cluster on chromosome 9pARTHRITIS & RHEUMATISM, Issue 5 2006Haoyang Zhuang Objective Systemic lupus erythematosus (SLE) is associated with type I interferons (IFNs) and can be induced by IFN, treatment. This study looked for evidence of autoimmunity in a pedigree consisting of 4 family members with a balanced translocation 9;21 and 2 members with an unbalanced translocation resulting in trisomy of the short (p) arm and part of the long (q) arm of chromosome 9. These latter 2 subjects had 3 copies of the IFN gene cluster. Methods Subjects were evaluated clinically and serologically for autoimmune disease. Expression levels of IFN,4, IFN,, the type I IFN,inducible gene Mx1, the type I IFN receptor, interleukin-6, and tumor necrosis factor , were determined by real-time polymerase chain reaction. Circulating plasmacytoid dendritic cells, the main IFN-producing cells, were quantified by flow cytometry. Results Both subjects with trisomy of chromosome 9p had a lupus-like syndrome with joint manifestations and antinuclear antibodies: one had anti-RNP and antiphospholipid autoantibodies, and the other had anti,Ro 60. The 3 family members with a balanced translocation 9;21 had no clinical or serologic evidence of autoimmunity, similar to that in relatives who were unaffected by the chromosomal translocation. In the 2 subjects with trisomy of 9p, high levels of IFN,/, (comparable with those found in patients with SLE), increased signaling through the IFN receptor (as indicated by high Mx1 expression), and low levels of circulating plasmacytoid dendritic cells (as observed in patients with SLE) were evident. These abnormalities were not seen in individuals with a balanced translocation. Conclusion Trisomy of the type I IFN cluster of chromosome 9p was associated with lupus-like autoimmunity and increased IFN,/, and IFN receptor signaling. The data support the idea that abnormal regulation of type I IFN production is involved in the pathogenesis of SLE. [source] Hypoxia and low-nutrition double stress induces aggressiveness in a murine model of melanomaCANCER SCIENCE, Issue 5 2009Tsuyoshi Osawa Antiangiogenic therapy is a potent cancer treatment, however, the possibility of recurrence and resistance to this approach remains. Here we show that hypoxia and low-nutrition double-deprivation stress induces reversible tumor aggressiveness. In a stress-cycle-dependent manner, murine melanoma cells showed morphological changes, up-regulated phospho-Akt, and abnormal regulation of multiple genes including fibroblast growth factor-21, a metabolic regulator, resulting in increased cell proliferation in vitro, and increased tumorigenesis and invasive potential in vivo. In this system, altered cellular metabolism participates in the adaptation of tumor to the double-deprivation stress. Our results suggest the targeting of a minor population of cancer cells resistant to both hypoxia and low nutrition to be an effective new antitumor strategy in combination with antiangiogenic therapy. (Cancer Sci 2009; 100: 844,851) [source] Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunctionCLINICAL ENDOCRINOLOGY, Issue 1 2010André Lacroix Summary The aberrant adrenal expression and function of one or several G-protein coupled receptors can lead to cell proliferation and abnormal regulation of steroidogenesis in unilateral adenomas, carcinomas or in ACTH-independent macronodular adrenal hyperplasia (AIMAH). Excess cortisol secretion leading to either sub-clinical or overt Cushing's syndrome is the most prevalent phenotype reported to date. In a few patients, aberrant regulation of androgen excess has been reported. More recently, initial studies suggest that similar mechanisms are involved in the renin-independent regulation of aldosterone secretion in primary aldosteronism. In recent years, cases of familial AIMAH have been identified, and specific aberrant hormone receptors are functional in the adrenal of affected members. The identification of aberrant receptors can offer specific pharmacological approach to prevent disease progression and control abnormal steroidogenesis; alternatively, unilateral or bilateral adrenalectomy remains the treatment of choice. [source] | ||||||||||