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Biomedical subjects

M A Fiedler

Publications and source records attributed to M A Fiedler.

27 records · Page 2Linked to original sources

Respiratory syncytial virus increases IL-8 gene expression and protein release in A549 cells.

The mechanism of respiratory syncytial virus (RSV)-induced inflammation in the airways of infants and children is not fully understood. We hypothesized that RSV directly induces interleukin (IL)-8 gene expression in airway epithelial cells, independent of IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) production. Exposure of A549 cells (an airway epithelial cell line) to RSV resulted in increased IL-8 mRNA expression and IL-8 protein release from the cells as early as 2 h after treatment. Neither IL-1 beta nor TNF-alpha (mRNA or protein) were detected. Viral replication was not necessary for the effects of RSV on IL-8 mRNA expression and protein release early in the infectious process. However, sustained levels of increased IL-8 production required RSV replication. A dose-response relationship was observed between the multiplicity of infection and IL-8 production with both active and nonreplicative RSV at the 2-h time point. Both active RSV and nonreplicative RSV increased the transcriptional activity of the 1.6-kb 5' flanking region of the IL-8 gene. Neither active RSV nor nonreplicative RSV increased the stability of the IL-8 mRNA in A549 cells. We conclude that RSV increases IL-8 gene expression in A549 cells in a biphasic pattern independent of viral replication early (2 h) but dependent on viral replication late (24 h).

Animals↗

Recent advances in the treatment of cystic fibrosis.

Cystic fibrosis is a serious, common genetic condition that causes recurrent pulmonary infections, malabsorption, and increased sweat electrolytes. Despite significant improvements in clinical treatment, individuals continue to die from progressive, obstructive pulmonary disease as children and young adults. This article reviews the current status of our understanding of cystic fibrosis: the basic defect, animal models, current therapy, and new approaches to the pulmonary disease.

Amiloride↗

Cloning and sequence analysis of rat cystic fibrosis transmembrane conductance regulator.

A complementary DNA (cDNA) encoding the rat cystic fibrosis transmembrane conductance regulator (CFTR) has been isolated and the tissue distribution of the rat CFTR mRNA has been determined. Northern blot analysis revealed that the highest levels of the 6.3 kilobase (kb) CFTR mRNA were expressed in the colon, with expression also noted in uterus, lung, stomach, and small intestine. A 7.5-kb mRNA was expressed in skeletal muscle, and in testes both the 7.5-kb mRNA and a 6.0-kb mRNA were expressed. Five cDNAs were isolated from a rat colon library, the longest corresponding to codons 684 through the poly A tail. Three other clones, corresponding to codons 213 through 245, 372 through 574, and 656 through 886 were also isolated. Polymerase chain reaction amplification of cDNA prepared from rat colon mRNA was utilized to clone the remainder of the cDNA. The predicted amino acid sequence of the rat CFTR is 79% identical to the human CFTR, with 73% identity noted in the R domain, and 81 and 83% identities noted in nucleotide binding folds 1 and 2, respectively. Thirty-two of the 38 potential phosphorylation sites identified in the human CFTR were also present in the rat CFTR.

Animals↗

Sustained production of secretory component by human tracheal epithelial cells in primary culture.

Secretory immunoglobulin A (sIgA) is an important initial defense against environmental agents in the airway. The purposes of our study were to determine whether human tracheal epithelial (HTE) cells produce secretory component (SC), the receptor for dimeric IgA (dIgA), to determine whether HTE cells in primary culture continue to produce SC, and if so, to develop a model for studying SC metabolism in the airway. Immunoperoxidase staining of the human trachea using antibody raised against human SC reveals that many surface epithelial cells and the cells of the submucosal glands express SC but basal cells do not. HTE cells, obtained from tracheal specimens at necropsy, contain 10-51 ng of SC/10(5) cells, at the time of isolation. However, when these cells are placed in culture on plastic, SC release diminishes with time (from 19.6 ng/10(5) cells on day 2 to 6.4 on day 8) despite continued cell proliferation. In contrast, HTE cells cultured on floating collagen gels increase SC release over the same period (26.2 ng/10(5) cells on day 2 and 193.9 on day 8). HTE cells cultured on collagen-coated and uncoated nitrocellulose filters also produced SC at least through day 8 (collagen coated, 21.5 ng/10(5); uncoated, 6.3). Furthermore, SC was released preferentially to the apical surface (4:1 ratio) under both conditions. This system will allow us to study the production, processing, and release of SC by HTE cells and further understand the transport and function of secretory IgA in the airway.

Biological Transport↗

Esmolol and beta-adrenergic blockade.

Tachycardia often presents difficult management problems in anesthesia. Because it increases myocardial oxygen demand so sharply, tachycardia can quickly place patients at risk of myocardial ischemia. It can occur for any number of reasons. Deepening the anesthetic, either with inhalation agent or opioids, will ablate increases in heart rate, but changes in heart rate are often transient and changes in anesthetic depth are often not. Esmolol (Brevibloc) is a unique, short-acting beta blocker that is strongly beta 1 selective at usual clinical doses. As with other beta blockers, esmolol becomes less selective for the beta 1 receptor as its dose is increased. It is metabolized by red blood cell esterases resulting in a half-life of 9 minutes. Fifteen minutes after a bolus dose, esmolol is difficult to detect in the plasma. Its metabolites have clinically undetectable activity and are eliminated renally. Esmolol may be administered by intermittent, intravenous bolus doses or by continuous infusion. Infusions should be preceded by loading doses. Dose range varies with the patient's status, clinical situation, concomitant medications, and desired result. Patients receiving esmolol should be monitored because of its bradycardic and hypotensive effects.

Adrenergic beta-Antagonists↗

AANA Journal course: new technologies in anesthesia: update for nurse anesthetists--the computer-generated anesthesia record.

This lesson will introduce the anesthetist to computerized anesthesia record keepers, their history, development and current technology. It will identify some of the outstanding advantages and disadvantages of computerized record keepers from both clinical and legal standpoints. Computerized record keepers may not assume charting duties during all anesthetics administered in the United States but they do offer many advantages, especially during difficult cases. As their development continues, they may relieve the anesthetist of some repetitive and distracting tasks while providing clinically useful information and analysis.

Education, Nursing, Continuing↗

AANA Journal course: advanced scientific concepts: update for nurse anesthetists--an introduction to fetal heart rate monitoring.

Although not actually a new technology, fetal heart rate monitoring is a technology that many anesthetists know little or nothing about. Even those who regularly provide anesthesia care for obstetric patients frequently know only what is picked up along the way. The following lesson provides an introduction to the most commonly encountered and clinically important fetal heart rate patterns. With this information, the well-being of the fetus can be considered when making a preanesthesia or intra-anesthetic assessment of a pregnant patient.

Education, Nursing, Continuing↗