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H L Crocker J Pfitzner I R Doyle W M Hague B J Smith R E Ruffin 《The European respiratory journal》2000,15(2):426-429
Pulmonary alveolar proteinosis is a rare condition characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. Two cases with contrasting modes of presentation, course, and response to therapeutic whole lung lavage are described. Both cases were in hypoxaemic respiratory failure at the time the definitive diagnosis was made, and in both cases the diagnosis was made by segmental bronchoalveolar lavage following negative open lung biopsy. In neither was an underlying causative organism or agent identified. In one case the alveolar proteinosis developed in late pregnancy, a presentation that is previously unreported. Clinical improvement in this case required repeated whole lung lavages and was accompanied by a trend towards normalization of the ratios of surfactant protein-A and surfactant protein-B to disaturated phospholipid, ratios which may be useful as prognostic indicators. The response to therapeutic lavage was markedly different in the two cases, and it is postulated that this may relate to the fact that alveolar proteinosis is a heterogeneous disease and that the course and response to treatment may relate in part to the specific composition of the abnormal proteinaceous fluid. 相似文献
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Premature ovarian failure accounts for 10% of cases of secondary amenorrhea, and in most cases its cause remains unknown. One mechanism by which it occurs is autoimmune destruction. A 21-year-old patient is described in whom autoimmune ovarian failure occurred in association with Addison's disease and primary hypothyroidism. Although premature ovarian failure is generally considered irreversible, the patient subsequently resumed spontaneous ovarian follicular activity. 相似文献
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W M Hague 《British medical journal (Clinical research ed.)》1987,294(6567):297-300
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The N terminus of the human alpha1D-adrenergic receptor prevents cell surface expression 总被引:2,自引:0,他引:2
Hague C Chen Z Pupo AS Schulte NA Toews ML Minneman KP 《The Journal of pharmacology and experimental therapeutics》2004,309(1):388-397
We previously reported that truncation of the N-terminal 79 amino acids of alpha(1D)-adrenoceptors (Delta(1-79)alpha(1D)-ARs) greatly increases binding site density. In this study, we determined whether this effect was associated with changes in alpha(1D)-AR subcellular localization. Confocal imaging of green fluorescent protein (GFP)-tagged receptors and sucrose density gradient fractionation suggested that full-length alpha(1D)-ARs were found primarily in intracellular compartments, whereas Delta(1-79)alpha(1D)-ARs were translocated to the plasma membrane. This resulted in a 3- to 4-fold increase in intrinsic activity for stimulation of inositol phosphate formation by norepinephrine. We determined whether this effect was transplantable by creating N-terminal chimeras of alpha(1)-ARs containing the body of one subtype and the N terminus of another (alpha(1A)NT-D, alpha(1B)NT-D, alpha(1D)NT-A, and alpha(1D)NT-B). When expressed in human embryonic kidney 293 cells, radioligand binding revealed that binding densities of alpha(1A)-or alpha(1B)-ARs containing the alpha(1D)-N terminus decreased by 86 to 93%, whereas substitution of alpha(1A)- or alpha(1B)-N termini increased alpha(1D)-AR binding site density by 2- to 3-fold. Confocal microscopy showed that GFP-tagged alpha(1D)NT-B-ARs were found only on the cell surface, whereas GFP-tagged alpha(1B)NT-D-ARs were completely intracellular. Radioligand binding and confocal imaging of GFP-tagged alpha(1D)- and Delta(1-79)alpha(1D)-ARs expressed in rat aortic smooth muscle cells produced similar results, suggesting these effects are generalizable to cell types that endogenously express alpha(1D)-ARs. These findings demonstrate that the N-terminal region of alpha(1D)-ARs contain a transplantable signal that is critical for regulating formation of functional bindings, through regulating cellular localization. 相似文献
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