Flow rate and inorganic components of submandibular saliva in cystic fibrosis

Blomfield, Jeanette; Warton, Kathryn L.; Brown, Jennifer M.

doi:10.1136/adc.48.4.267

Cited by 55 publications

(44 citation statements)

References 17 publications

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“…In a human body, Ca 2ϩ levels may reach about 1 to 2 mM in extracellular fluids and saliva (11) (12) and 5 mM in blood (13) and human milk (14). In the case of disease, for example, during cystic fibrosis (CF) pulmonary infections, both intracellular and extracellular Ca 2ϩ levels fluctuate in response to inflammation (15,16), and the overall Ca 2ϩ levels in nasal secretions and sputum increase at least 2-fold (12), reaching up to 3 to 7 mM (17,18).…”

mentioning

confidence: 99%

The Pseudomonas aeruginosa PAO1 Two-Component Regulator CarSR Regulates Calcium Homeostasis and Calcium-Induced Virulence Factor Production through Its Regulatory Targets CarO and CarP

et al. 2016

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Pseudomonas aeruginosa is an opportunistic human pathogen that causes severe, life-threatening infections in patients with cystic fibrosis (CF), endocarditis, wounds, or artificial implants. During CF pulmonary infections, P. aeruginosa often encounters environments where the levels of calcium (Ca 2؉ ) are elevated. Previously, we showed that P. aeruginosa responds to externally added Ca 2؉ through enhanced biofilm formation, increased production of several secreted virulence factors, and by developing a transient increase in the intracellular Ca 2؉ level, followed by its removal to the basal submicromolar level. However, the molecular mechanisms responsible for regulating Ca . In addition, a mutation in carP had a pleotropic effect in a Ca 2؉ -dependent manner, altering swarming motility, pyocyanin production, and tobramycin sensitivity. Overall, the results indicate that the two-component system CarSR is responsible for sensing high levels of external Ca 2؉ and responding through its regulatory targets that modulate Ca 2؉ homeostasis, surface-associated motility, and the production of the virulence factor pyocyanin. P seudomonas aeruginosa, a natural inhabitant of soil and water, is able to infect a variety of hosts, including plants and humans. In humans, it causes severe acute and chronic infections by colonizing respiratory and urinary tracts and burned or wounded epithelia, cornea, and muscles (1-3). The versatility of P. aeruginosa pathogenicity is associated with diverse metabolic capabilities, multiple mechanisms of resistance, a large repertoire of virulence factors, and adaptability, due in part to the tightly coordinated regulation of gene expression. A large portion of the P. aeruginosa PAO1 genome, approximately 9.4%, encodes transcriptional regulators (4, 5), including two-component regulators: 89 response regulators, 55 sensor kinases, and 14 sensorresponse regulator hybrids (2). The regulatory targets for most of these regulatory systems are unknown. IMPORTANCE During infectious disease,Calcium plays an important signaling role in both eukaryotic and prokaryotic cells. In prokaryotes, Ca 2ϩ is an essential nutrient, since it is a necessary cofactor for many enzymes. However, Ca 2ϩ can be toxic to cells at high concentrations; therefore, bacteria maintain a low-submicromolar intracellular concentration of Ca 2ϩ (6). P. aeruginosa may encounter environments where

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confidence: 99%

The Pseudomonas aeruginosa PAO1 Two-Component Regulator CarSR Regulates Calcium Homeostasis and Calcium-Induced Virulence Factor Production through Its Regulatory Targets CarO and CarP

et al. 2016

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“…Citric acid-stimulated submandibular saliva was collected by a modification of the method of Mandel, Hypersecretion of zymogen granules in the pathogenesis of cystic fibrosis Eriv, Kutscher, Denning, Thompson, Kessler, and Zegarelli (1969), as previously outlined (Blomfield et al, 1973). The subjects were 10 patients with cystic fibrosis aged from 6 to 15 years (five male and five female), and from 10 healthy controls aged from 8 to 19 years (five male and five female).…”

Section: Methodsmentioning

confidence: 99%

Hypersecretion of zymogen granules in the pathogenesis of cystic fibrosis

Blomfield¹,

Dascalu²,

Lennep³

et al. 1973

Gut

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“…There are inconsistent and conflicting reports on the effect of CF on salivary gland functions. Abnormal Cl 2 absorption and HCO 3 2 secretions by the submandibular gland ducts were observed from CF patients (Blomfield et al 1973;Davies et al 1989Davies et al , 1991McPherson et al 1992). Several studies have indicated functional and pathological abnormalities in salivary gland functions.…”

Section: Salivary Glandsmentioning

confidence: 99%