81 results found
Bhavsar PK, Sukkar MB, Khorasani N, et al., 2008, Glucocorticoid suppression of CX(3)CL1 (fractalkine) by reduced gene promoter recruitment of NF-kappa B, FASEB JOURNAL, Vol: 22, Pages: 1807-1816, ISSN: 0892-6638
Adcock IM, Ford PA, Bhavsar P, et al., 2008, Steroid resistance in asthma: Mechanisms and treatment options, CURRENT ALLERGY AND ASTHMA REPORTS, Vol: 8, Pages: 171-178, ISSN: 1529-7322
Bhavsar P, Adcock IM, 2008, Molecular Mechanisms of Glucocorticoid Receptor Action, Pages: 1-18
Glucocorticoids are the most effective therapy for the treatment of many chronic inflammatory diseases but they are ineffective in severe asthma and chronic obstructive pulmonary disease (COPD) for example. Glucocorticoids act by binding to and activating specific cytosolic receptors (GR). These receptors then translocate to the nucleus where they regulate gene expression. GR is able to selective repress specific inflammatory genes by differing actions on promoter-specific components of NF-κB and AP-1 activation complexes and also by effects on MAPK pathways. Importantly, these actions are mutually inhibitory. These pleitropic effects of GR may underlie there effectiveness in most patients with airways disease but suggests that abnormal activation of these pathways may result in glucocorticoid refractoriness. Understanding the molecular mechanisms of GR action may lead to the development of new anti-inflammatory drugs or enable clinicians to reverse the relative steroid-insensitivity that is characteristic of severe asthma and COPD for example. © 2008 John Wiley & Sons, Ltd.
Bhavsar P, Ahmad T, Adcock IM, 2008, The role of histone deacetylases in asthma and allergic diseases, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 121, Pages: 580-584, ISSN: 0091-6749
Diverse cellular functions including the regulation of inflammatory gene expression, DNA repair and cell proliferation are regulated by epigenetic changes. Transcriptional co-activators possess intrinsic histone acetyltransferase (HAT) activity, and histone acetylation plays a major role in inflammatory gene expression. Other marks such as histone methylation are also associated with gene induction and gene repression. Recent evidence implicates histone acetylation and methylation as being crucial for the development of tolerance in macrophages and CpG methylation for T regulatory cell development and function. The expression of the enzymes that lay down or remove these epigenetic marks have not been well studied in human airways disease, but reduced HDAC2 expression and activity is reported in lung macrophages, biopsies and blood cells from patients with COPD, severe asthma and smoking asthma. In vitro, inhibitors of histone deacetylases (HDAC) often lead to a further induction of inflammatory gene expression. This is not always the case, however, as HATs and HDACs also target non-histone proteins particularly transcription factors to alter their activity. Furthermore, trichostatin A, an HDAC inhibitor, can reduce inflammation in a murine model of allergic asthma. This effect of HDAC inhibitors may be due to their effects on cell death acting through acetylation of non-histone proteins. The role of epigenetic modifications in inflammatory gene expression and in the control of cell function in the airways is becoming clearer. Targeting specific enzymes involved in this process may lead to new therapeutic agents, in particular, in situations where current anti-inflammatory therapies are currently suboptimal.
Williams AS, Leung S-Y, Nath P, et al., 2007, Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophilia, JOURNAL OF APPLIED PHYSIOLOGY, Vol: 103, Pages: 1189-1195, ISSN: 8750-7587
Hew M, Bhavsar P, Torrego A, et al., 2006, Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 174, Pages: 134-141, ISSN: 1073-449X
Issa R, Xie S, Lee K-Y, et al., 2006, GRO-alpha regulation in airway smooth muscle by IL-1 beta and TNF-alpha: role of NF-kappa B and MAP kinases, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 291, Pages: L66-L74, ISSN: 1040-0605
Xie SP, Issa RA, Sukkar MB, et al., 2005, Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells, Respiratory Research, Vol: 6, ISSN: 1465-993X
Santalucia T, Sanchez-Feutrie M, Felkin LE, et al., 2005, Phenylephrine requires the TATA box to activate transcription of GLUT1 in neonatal rat cardiac myocytes, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 38, Pages: 677-684, ISSN: 0022-2828
Bhavsar PK, Felkin LE, Barton PJR, et al., 2002, Molecular and morphological effects of clenbuterol on neonatal rat cardiac myocytes in culture, Congress of the European-Society-of-Cardiology, Publisher: W B SAUNDERS CO LTD, Pages: 369-369, ISSN: 0195-668X
Dellow KA, Bhavsar PK, Brand NJ, et al., 2001, Identification of novel, cardiac-restricted transcription factors binding to a CACC-box within the human cardiac troponin I promoter, CARDIOVASCULAR RESEARCH, Vol: 50, Pages: 24-33, ISSN: 0008-6363
Bhavsar PK, Dellow KA, Yacoub MH, et al., 2000, Identification of cis-acting DNA elements required for expression of the human cardiac troponin I gene promoter, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 32, Pages: 95-108, ISSN: 0022-2828
Barton PJR, Cullen ME, Townsend PJ, et al., 1999, Close physical linkage of human troponin genes: Organization, sequence, and expression of the locus encoding cardiac troponin I acid slow skeletal troponin T, GENOMICS, Vol: 57, Pages: 102-109, ISSN: 0888-7543
Barton PJ, Townsend PJ, Brand NJ, et al., 1997, Genes encoding the striated muscle thin filament proteins troponin I and troponin T are organised in paralogous pairs at three chromosomal sites, Publisher: AMER HEART ASSOC, Pages: 1315-1315, ISSN: 0009-7322
Bhavsar PK, Brand NJ, Yacoub MH, et al., 1996, Isolation and characterization of the human cardiac troponin I gene (TNNI3), GENOMICS, Vol: 35, Pages: 11-23, ISSN: 0888-7543
BHAVSAR PK, BRAND NJ, YACOUB MH, et al., 1993, THE HUMAN CARDIAC TROPONIN-I GENE - A MODEL FOR CARDIAC-SPECIFIC REGULATION, JOURNAL OF CELLULAR BIOCHEMISTRY, Pages: 189-189, ISSN: 0730-2312
BRAND NJ, DABHADE N, BHAVSAR PK, et al., 1993, IDENTIFICATION OF ZINC FINGER AND SRY-LIKE TRANSCRIPTION FACTORS EXPRESSED IN HUMAN HEART, JOURNAL OF CELLULAR BIOCHEMISTRY, Pages: 190-190, ISSN: 0730-2312
BARTON PJR, BHAVSAR PK, BRAND NJ, et al., 1992, GENE-EXPRESSION DURING CARDIAC DEVELOPMENT, SYMP ON MOLECULAR BIOLOGY OF MUSCLE, Publisher: COMPANY BIOLOGISTS LTD, Pages: 251-264, ISSN: 0081-1386
Barton PJ, Bhavsar PK, Brand NJ, et al., 1992, Gene expression during cardiac development., Pages: 251-264
The vertebrate heart forms as two concentric epithelial cylinders of myocardium and endocardium separated by an extended basement membrane matrix commonly referred to as cardiac jelly. Subsequent maturation involves a complex series of events including asymmetric changes in cell shape and division which contribute to bending and the formation of the bulboventricular loop, the formation of specialised tissues including endocardial cushion tissue of the atrioventricular (AV) and outflow tract regions, the development of conductive tissue and myocyte maturation leading to the overall pattern of expression characteristic of mature heart muscle. These processes depend on a precise spatial and temporal control of gene expression both of genes encoding regulatory molecules and those encoding structural components of the heart. In this chapter we address three aspects of cardiac development, namely, the determination of cell fate during formation of endocardial cushion tissue in the embryonic heart, transitions in troponin gene expression during fetal myocyte maturation, and the use of cloning techniques based on the polymerase chain reaction for identifying transcription factors present in the heart.
BHAVSAR PK, DHOOT GK, CUMMING DVE, et al., 1991, DEVELOPMENTAL EXPRESSION OF TROPONIN-I ISOFORMS IN FETAL HUMAN HEART, FEBS LETTERS, Vol: 292, Pages: 5-8, ISSN: 0014-5793
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.