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1.
《Developmental cell》2022,57(18):2221-2236.e5
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2.
Deborah Shaw Ian R. Poxton John R.W. Govan 《FEMS immunology and medical microbiology》1995,11(2):99-106
Abstract Burkholderia cepacia has emerged as an important multiresistant pathogen in cystic fibrosis (CF), associated in 20% of colonised patients with a rapid and fatal decline in lung function. Although knowledge of B. cepacia epidemiology has improved, the mechanisms involved in pathogenesis remain obscure. In this study, B. cepacia lipopolysaccharide (LPS) was assessed for endotoxic potential and the capacity to induce tumour necrosis factor (TNF). LPS preparations from clinical and environmental isolates of B. cepacia and from the closely related species Burkholderia gladioli exhibited a higher endotoxic activity and more pronounced cytokine response in vitro compared to preparations from the major CF pathogen Pseudomonas aeruginosa . This study may help to explain the vicious host immune response observed during pulmonary exacerbations in CF patients colonised by B. cepacia and lead to therapeutic advances in clinical management. 相似文献
3.
《European journal of cell biology》2022,101(3):151234
Patients with idiopathic pulmonary fibrosis (IPF) have a high risk of developing lung cancer compared with the general population. The morbidity of lung cancer in IPF patient ranges from 3% to 22%, and in some cases exceeds 50%, and these patients have a reduced survival time. However, the mechanisms through which IPF increases the morbidity and mortality in lung cancer remain unclear.By carefully analyzing the pathological features of these two diseases, we uncovered that, first, similar to IPF, lung carcinomas are more frequently found in the peripheral area of the lungs and, second, lung cancers tend to develop from the honeycomb areas in IPF. In accordance with the above pathological features, due to the spatial location, the peripheral areas of the lung experience a high stretch force because the average distance between adjacent alveolar cells in this area tends to be larger than that at the central lung when inflated; furthermore, the honeycomb areas, comprised of condensed fibrous tissue, are characterized by increased stiffness. Both of these pathological features of lung cancer and IPF are coincidentally related to abnormal mechanical forces (stretch and tissue stiffness). Therefore, we believe that the aberrant mechanical forces that are generated in the lung with IPF may contribute to the onset and progression of lung cancer.In this review, we discuss the possible effects of mechanical forces that are generated in IPF on the initiation and progression of lung cancer from the perspective of the hallmarks of cancer, including proliferation, metastasis, angiogenesis, cancer stem cells, immunology, epigenetics, and metabolism, so as to advance our understanding of the pathogenesis of IPF-related lung cancer and to harness these concepts for lung cancer mechanotherapies. 相似文献
4.
There have been numerous reports in the literature describing the diversity of microbial flora isolated from woodwind and brass instruments, with potential infection risks for players, especially when such instruments are shared. Steam disinfection has become established as a trusted method of decontamination; however, there have been no reports on the employment of this technology to disinfect parts of musical instruments, hence it was the aim of this study to examine the fate of bacterial and yeast pathogens on artificially contaminated trumpet mouthpieces and to evaluate whether such disinfection is an effective method of disinfection for such instrument parts. Trumpet mouthpieces were artificially contaminated with 18 microbial strains (17 bacteria from four genera (Enterococcus, Escherichia, Staphylococcus and Streptococcus) and one yeast (Candida)), each at an inoculum density of approximately 1·5 × 107 colony forming units and subjected to a disinfection cycle. The experiment was repeated including 50% (v/v) sterile sputum as soil. No bacteria or yeast organisms were recovered post disinfection, including following recovery and with nonselective cultural enrichment techniques. 相似文献
5.
6.
A biochemical link is proposed between recent observations on defective regulation of Cl– transport in CF respiratory epithelial cells and studies showing altered biological activity of calmodulin in exocrine glands from CF patients. A consensus is emerging that defective -adrenergic secretory responsiveness in CF cells is caused by a defect in a regulator protein at a site distal to cyclic AMP formation. Our results indicate that this protein might be a specific calmodulin acceptor protein which modifies the activity of calmodulin in epithelial cells. Alteration in Ca2+/calmodulin dependent regulation of Cl– transport and protein secretion could explain (i) alterations in Ca2+ homeostasis seen in CF, (ii) defective -adrenergic responses of CF cells, and (iii) the observed inability of cyclic AMP (acting via its specific protein kinase, A-kinase) to open apical membrane Cl– channels in CF epithelial cells. Most of the physiological abnormalities of CF including elevated sweat electrolytes and hyperviscous mucus can be explained on this basis.Abbreviations -adrenergic agonist acting at its receptor cAMP
cyclic AMP
- PDE
phosphodiesterase
- CaM
calmodulin
- Pase
phosphatase 相似文献
7.
Summary The effect of pH buffers and related compounds on the conductance of an outwardly rectifying anion channel has been studies using the patch-clamp technique. Single-channel current-voltage relationships were determined in solutions buffered by trace amounts of bicarbonate and in solutions containing N-substituted taurines (HEPES, MES, BES, TES) and glycines (glycylglycine, bicine and tricine), Tris andbis-Tris at millimolar concentrations. HEPES (pKa=7.55) reduced the conductance of the channel when present on either side of the membrane. Significant inhibition was observed with 0.6mm HEPES on the cytoplasmic side (HEPES
i
) and this effect increased with [HEPES
i
] so that conductance at the reversal potential was diminished 25% with 10mm HEPES
i
)and 70% at very high [HEPES
i
]. HEPES
i
block was relieved by applying positive voltage but positive currents were not consistent with a Woodhulltype blocking scheme in that calculated dissociation constants and electrical distances depended on HEPES concentration. Results obtained by varying total HEPES
i
concentration at constant [HEPES–] and vice versa suggest both the anionic and zwitterionic (protonated) forms of HEPES inhibit. Structure-activity studies with related compounds indicate the sulfonate group and heterocyclic aliphatic groups are both required for inhibition from the cytoplasmic side. TES (pKa=7.54), substituted glycine buffers (pKa=8.1–8.4) andbis-Tris (pKa=6.46) had no measurable effect on conductance and appear suitable for use with this channel. 相似文献
8.
Summary Chloride ions (Cl–) are concentrated in airway epithelial cells and subsequently secreted into the tracheal lumen by downhill flux through apical Cl– channels. We have studied Cl– currents in cultured canine tracheal cells using the whole-cell voltage-clamp technique. Ultrastructural techniques demonstrated that the cells used in the electrophysiological experiments possessed apical membrane specializations known to be present in the intact, transporting cell type. Cultured cells 2–6 days old were characterized by an input resistance of 3.4±0.8 G (n=11) and a capacitance of 63.8±10.8 pF (n=26). A comparison of 3 and 4 day-old cells with 5 and 6 day-old cells showed that the input resistance decreased almost 50%, and the cell capacitance and the inward and outward currents increased concomitantly approximately 200%. Cultured cells 3–4 days old held at –40 mV produced currents of 196±22 pA at 50 mV and –246±27 pA at –90 mV (n=212) with pipette and bath solutions containing primarily 140 KCl and 140 NaCl, respectively. The chloride channel blocker diphenylamine-2-carboxylate (DPC, 100 m) suppressed whole-cell currents by 76.8% at 60 mV; however, currents were unaffected by the stilbenes SITS (1mm) and DNDS (1–30 m). Replacement of K+ with Cs+ in the pipette solution did not affect the outward current, the current reversal potential, or the input resistance of the cells, indicating that the current was not significantly K+ dependent when the intrapipette solution was buffered to a Ca2+ concentration of 20nm. The Cl–/Na+ permeability ratio was estimated to be greater than 11 as calculated from reversal potential measurements in the presence of an internal to external NaCl concentration ratio of 12. Current equilibrium permeabilities, relative to Cl– were: I– (2.9)NO
3
–
(1.1)Br– (1.1)Cl– (1.0)F– (0.93)MeSO
4
–
(0.19)gluconate (0.18)aspartate (0.14). Depolarizations to potentials greater than 20 mV elicited a time-dependent component in the outward current in 71% of the cells studied. Currents inactivated with a double exponential time course at the most depolarized voltages. Recovery from inactivation was fast, holding potential-dependent, and followed a double exponential time course. Current amplitude was increased via a cAMP-dependent pathway as has been demonstrated for single Cl-selective channels in cell-attached patches from cultured canine and human tracheal epithelial cells. Forskolin, an activator of adenylate cyclase, produced a 260% increase in the outward current at +50 mV. In summary, cultured canine tracheal cells have a single resting conductance that is Cl– selective, voltage-dependent, and modulated by a cAMP-dependent mechanism. This preparation appears to be appropriate for analysis of cellular modulation of airway Cl– channels and Cl– secretion. 相似文献
9.
Swelling and Ca2+-activated Anion Conductances in C127 Epithelial Cells Expressing WT and ΔF508-CFTR
CFTR is a chloride channel that is required for fluid secretion and salt absorption in many exocrine epithelia. Mutations
in CFTR cause cystic fibrosis. CFTR expression influences some ion channels, but the range of channels influenced, the mechanism
of the interaction and the significance for cystic fibrosis are not known. Possible interactions between CFTR and other ion
channels were studied in C127 mouse mammary epithelial cell lines stably transfected with CFTR, ΔF508-CFTR, or vector. Cell
lines were compared quantitatively using an 125I efflux assay and qualitatively using whole-cell patch-clamp recording. As expected, 125I efflux was significantly increased by forskolin only in the CFTR line, and forskolin-stimulated whole-cell currents were
time- and voltage independent. All three lines responded to hypotonic challenge with large 125I efflux responses of equivalent magnitude, and whole-cell currents were outwardly rectified and inactivated at positive voltages.
Unexpectedly, basal 125I efflux was significantly smaller in the ΔF508-CFTR cell line than in either the CFTR or control cell lines (P < 0.0001), and the magnitude of the efflux response to ionomycin was largest in the vector cell line and smallest in the
cell line expressing ΔF508-CFTR (P < 0.01). Whole-cell responses to ionomycin had a linear instantaneous I-V relation and activated at depolarizing voltages. Forskolin responses showed simple summation with responses to ionomycin
or hypotonic challenge. Thus, we found no evidence for interactions between CFTR and the channels responsible for swelling-mediated
responses. Differences were found in basal and ionomycin-stimulated efflux, but these may arise from variations in the clonally
selected cell lines that are unrelated to CFTR expression.
Received: 15 November 1995/Revised: 16 February 1996 相似文献
10.
Alvaro N. A. Monteiro Radovan Borojevic 《In vitro cellular & developmental biology. Animal》1995,31(2):149-155
Summary Liver connective tissue cells (LCTC) isolated from patients with fibrotic livers have morphological and biochemical characteristics
of myofibroblasts. We have examined the proliferation of LCTC derived from normal livers and from livers with fibrosis of
different etiologies, as well as proliferation of skin fibroblasts. We have compared proliferation rates in the presence of
fresh human serum and heat-inactivated serum. While skin fibroblast and LCTC from normal liver showed no difference, proliferation
of LCTC from fibrotic livers was markedly decreased in the presence of heat-inactivated serum. We demonstrate that the native
complement component C1 is a factor involved in the induction of DNA synthesis and proliferation of LCTC isolated from fibrotic
livers. We propose that native C1, acting probably in cooperation with other growth factors, is involved in the expansion
of connective tissue cells during the development of liver fibrosis. 相似文献