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Biomedical subjects

R Chowdhary

Publications and source records attributed to R Chowdhary.

9 recordsLinked to original sources
PubMed2006

Altered gene expression in human cells treated with the insecticide diazinon: correlation with decreased DNA excision repair capacity.

Many industrial and agricultural chemicals have steroid hormone agonist or antagonist activities and disrupt hormone-regulated gene expression. The widely-used agricultural insecticide, diazinon, was evaluated using MCF-7 cells - a breast cancer-derived, estrogen-dependent, human cell line - to examine the capacity of this chemical to alter steroid hormone-regulated gene expression. MCF-7 cells were treated with 30, 50, or 67 ppm of diazinon, and gene expression in treated cells was measured as mRNA levels in the cells compared to mRNA levels in untreated or estrogen-treated cells. DNA microarray analysis showed significant up- or down-regulation of a number of genes in treated cells compared to untreated cells. Of the 600 human genes on the chip utilized, specific genes with related functions were selected for additional consideration. Real time quantitative PCR (qrtPCR) completed to corroborate mRNA levels as a measure of specific gene expression, confirmed results obtained from analysis of the micro-array data. The data show that ERCC5, encoding Xeroderma pigmentosum protein G (XPG), essential for DNA excision repair, and ribonucleotide reductase subunit M1 (RNRM1), encoding a gene necessary for providing the nucleotides needed for DNA repair, were down-regulated in cells treated with diazinon. These studies were designed to provide base-line data on the gene expression-altering capacity of a specific agricultural chemical, diazinon, and allow assessment of some of the potentially deleterious effects associated with exposure of human cells to diazinon.

Cell Line, Tumor↗
PubMed2006

Alteration of gene expression in human cells treated with the agricultural chemical diazinon: possible interaction in fetal development.

Agricultural chemicals frequently alter human health or development, typically because they have endocrine agonist or antagonist activities and alter hormone-regulation of gene expression. The insecticide, diazinon, was evaluated for gene expression disrupting activity using MCF-7 cells, an estrogen-dependent human cell line, to examine the capacity of the insecticide to disrupt gene expression essential for morphological development, immune system development or function, and/or central nervous system development and function. MCF-7 cells were treated with 30, 50 or 67 ppm diazinon, and gene expression was measured in treated cells compared to expression in untreated or estrogen-treated cells. DNA microarray analysis of diazinon-treated cells showed significant up- or down-regulation of a large number of genes compared to untreated cells. Of the 600 human genes on the Phase 1 chip utilized for these studies, two specific genes--calreticulin and TGF-beta3--were selected for corroboration using quantitative real time PCR (qrtPCR). qrtPCR, completed to assess gene expression levels for calreticulin and TGFbeta3, confirmed results showing significant up-regulation of these two genes obtained from the microarray data. These studies were designed to provide baseline data on the gene expression-altering capacity of a specific chemical, diazinon, and allow a partial assessment of the potentially deleterious effects associated with exposure of human cells to this chemical. Currently, it is not known whether results from cells in vitro can be extrapolated to human health consequences of chemical exposure.

Agrochemicals↗
PubMed2004

Altered gene expression in human cells induced by the agricultural chemical Enable.

Steroid hormones bind to highly specific nuclear receptors, regulating gene expression that results in normal fetal growth and development and/or in normal adult physiological function. Many industrial and agricultural chemicals may bind one or more nuclear receptors, acting as mimics of steroid hormones, and are called endocrine disruptive chemicals (EDC) because they alter the expression of endocrine-regulated genes. A widely used fungicide, Enable (fenbuconazole), was evaluated to examine its capacity to alter endocrine-regulated gene expression. Cells of an oestrogen-dependent human breast cancer-derived line, MCF-7, were treated with a range, 0.033-3.3 ppb (ng/mL), of Enable, and gene expression was compared to that of untreated cells. Microarray analysis using a chip with 600 gene spots showed downregulation of eight genes and upregulation of 34 genes in cells treated with 3.3 ppb of Enable, compared to untreated cells. Specific genes were selected for consideration. Real-time PCR confirmed results obtained from analysis of the microarray data for the genes phenol sulphotransferase (PST), intercellular adhesion molecule-1 (ICAM-1), transforming growth factor beta-3 (TGF beta-3) and calreticulin. These studies were designed to provide base-line data on the gene expression-altering capacity of a specific chemical at a low dose, and will allow assessment of the possible deleterious effects that may be caused in human cells by exposure to the agricultural chemical Enable.

Agriculture↗
PubMed2000

The role of cough and hyperventilation in perpetuating airway inflammation in asthma.

Air flowing through a pipe exerts frictional stress on the walls of the pipe. Frictional stress of more than 40 N/m2 (velocity equivalent of air 113 m/s) is known to cause acute endothelial damage in blood vessels. The frictional stress in airways during coughing may be much greater, however, since the velocity of air may be as high as speed of sound in air. We suggest that high levels of frictional stress perpetuate airway inflammation in airways which are already inflamed and vulnerable to frictional stress-induced trauma in patients with asthma. Activities associated with rapid ventilation and higher frictional stress (e.g. exercise, hyperventilation, coughing, sneezing and laughing) cause asthma to worsen whilst activities that reduce frictional stress (Yoga 'Pranayama', breathing a helium-oxygen mixture and nasal continuous positive airway pressure) are beneficial. Therefore control of cough may have anti-inflammatory benefits in patients with asthma.

Asthma↗
PubMed2000

Does nasal breathing cause frictional trauma in allergic rhinitis?

OBJECTIVES: Frictional stress on the walls of a tube increases with increased air flow and as the diameter of the tube is reduced. High values of frictional stress may occur in the nose during nasal obstruction which could damage the nasal mucosa particularly when the mucosa is inflamed and fragile as in allergic rhinitis. The effect of nasal airflow induced frictional stress on the nasal mucosa was studied in patients with allergic rhinitis. METHODS: We studied nasal peak flow rate in eight patients with allergic rhinitis and nasal obstruction comparing the change in peak expiratory flow after they breathed for 30 minutes through an obstructed and a patent nostril. Patients were studied in the right and left lateral decubitus positions to increase and decrease the resistance in the lower and upper nostril respectively and thus minimize any effects of cyclical changes in nasal resistance. Subjects breathed for 30 minutes through the upper patent nostril (schedule 1) and for a further 30 minutes through the lower obstructed nostril (schedule 2). Nasal peak expiratory flow rate was measured in both nostrils separately in both positions after each schedule. RESULTS: There was a significant reduction in mean (SD) nasal peak flow rate (-12.8 (4.06) L/min) after subjects had breathed for 30 minutes through the obstructed nostril. There was no significant change in nasal peak flow rate after subjects had breathed through the patent nostril, or in the nostril that had no flow for 30 minutes. CONCLUSIONS: These findings are compatible with the hypothesis that frictional stress due to airflow through an obstructed nostril induces trauma and swelling of the nasal mucosa of patients with allergic rhinitis.

Adolescent↗
PubMed1999

Relationship of flow and cross-sectional area to frictional stress in airway models of asthma.

Frictional stress from air flowing through narrowed airways may damage the airway mucosa and thereby increase airway inflammation and airway obstruction. To investigate the levels of frictional stress that might occur in the airway, we measured the frictional stress in three physical airway models (model 1: normal state; models 2 and 3: narrowed states with cross-sectional area half and one-fourth of model 1, respectively) at tracheal expiratory flow rates of 1, 2, 3, 4, 5, 6, 7, and 8 L/sec. Frictional stress measured at stations in the trachea (A), two each in the left (B and C) and right (D and E) major bronchi, and one in the right secondary bronchus (F) indicated that at higher flow rates, high values of the frictional stress seen in model 3 (highest value being 139.2 N/m2 at 8 L/sec at station) could well damage the airway wall, especially during episodes of cough, and particularly when the mucosa is inflamed and friable as it is in asthmatic patients. Conversely, control of cough may have anti-inflammatory benefits in asthmatic patients.

Adult↗