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Surfactant-associated proteins (SP-A, SP-B) are increased proportionally to alveolar phospholipids in sheep silicosis (1993)

Lesur, Olivier ; Veldhuizen, Rudy A. W. ; Whitsett, Jeff A. ; [et al.]

Springer

Lung 171 (1993), S. 63-74

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ISSN: 1432-1750

Keywords: SP-A-SP-B-Surfactant-associated proteins ; Surface-tension-reducing activities ; Silicosis

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract In silicosis, a profile of surfactant overproduction associated with type II epithelial cell hypertrophy and hyperplasia has been documented. In addition, enhanced accumulation of surfactant-associated protein A (SP-A) has been seen in the rat model of acute silicosis by 2 independent groups, but the exact role of these surfactant changes in silicosis are incompletely understood. In this study we measured in lung lavage surfactant total phospholipids and surfactant-associated proteins A and B (SP-A, SP-B). In addition, the surface tension reducing activities of lipid extracts of bronchoalveolar lavage fluids (BALFs) in the sheep silicosis model were examined using a pulsating bubble surfactometer. Two groups of animals (n = 18) were investigated: a saline-exposed (PBS-PBS) group and a silica-exposed (Si-PBS) group. Total surfactant phospholipids in the silicotic sheep increased 2-fold over the control sheep values (p 〈 0.05), as previously reported. In addition, we found a substantial rise in total surfactant-associated proteins, with significant increase in SP-A (1.16 ± 0.22 µg/ml Si-PBS group vs. 0.70 ± 0.07 µg/ml PBS-PBS group, p 〈 0.05) and a parallel but not significant increase in SP-B (2.68 ± 0.90 µg/ml Si-PBS group vs. 1.10 ± 0.30 µg/ml PBS-PBS group). The surface-tension-reducing activities of alveolar fluid lipid extracts did not differ significantly between the groups (Si-PBS group at maximal bubble radius [Rmax]: 27.0 ± 1.6 and at minimal bubble radius [Rmin]: 1.0 ± 0.7 milli Newton/m, vs. PBS-PBS group Rmax: 27.0 ± 2.2 and Rmin: 0.7 ± 0.3 milli Newton/m at 4 min pulsation). The ratios of SP-A and SP-B to lipid phosphorus levels document a proportional enhancement of surfactant-associated proteins and phospholipids, thus suggesting a coordinated upregulation of both surfactant-associated proteins and phospholipids in this model of silicosis. However, on an individual basis, these changes were not related, suggesting a more complex model of regulation. This study documents significant increases of the surfactant apoproteins proportional to changes in phospholipids in the lung of silicotic sheep. In spite of these alterations of surfactant components, organic solvent lipid extracts of BAPLFs surfactant remained equally effective in reducing surface tension.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00542334

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Use of two-dimensional NMR and molecular modelling for the structure determination of novel cyclophosphamide derivatives: Diastereomers of 1-aza-2-bis(2-chloroethyl)- amino-3-oxa-2-oxo-2-phospha-7-thia-bicyclo- [4.4.0]decane and [4.3.0]nonaneThis paper is dedicated to Professor Hans-Georg Kuball, Dept. of Physical Chemistry, University of Kaiserslautern, on the occasion of his 60th birthday. (1992)

Schmidt, Brigitte F. ; Tang, Wei-Ci ; Eisenbrand, Gerhard ; [et al.]

Chichester : Wiley-Blackwell

Organic Magnetic Resonance 30 (1992), S. 1224-1240

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ISSN: 0749-1581

Keywords: Cyclophosphamides ; 1H NMR ; 13C NMR ; 31P coupling constants ; Molecular modelling ; Chemistry ; Analytical Chemistry and Spectroscopy

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Notes: High-field NMR studies at 11.7 T of newly synthesized diastereomeric 1-aza-2-bis(2-chloroethyl)amino-3-oxa-2- oxo-2-phospha-7-thia-bicyclo[4.4.0]decanes (4, 5) and the corresponding [4.3.0]nonanes (6, 7) were carried out by employing a combination of one- and two-dimensional homo- and heteronuclear methods. Unambiguous 31P, 1H and 13C chemical shift assignments for these bicyclic derivatives of cyclophosphamide were obtained, and the spin-spin couplings involving 1H, 13C and 31P were analysed in detail to determine the stereochemistry. Particularly useful were 1H J-resolved experiments, which separated phosphorus-proton couplings from proton-proton couplings, and 1H—13C shift-correlation experiments, which resolved the carbon-phosphorus couplings and provided information on the relative signs of J(P, H) and J(P,C). In addition, extensive molecular modelling calculations using various force-field (ALCHEMY, DISCOVER) and molecular orbital methods (MNDO, AM1, PM3) were carried out, and improved parameters for cyclophosphamides were developed for ALCHEMY. The diastereomeric pairs 4, 5 and 6, 7 differ in the axial vs. equatorial orientation of the sulphur substituent on the oxazaphosphorinane ring, which is itself exclusively in a chair conformation with axial P=O for all substances.

Additional Material: 4 Ill.