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Article
Activation of alveolar macrophage collagenase by a neutral protease secreted by the same cell
MAMMALIAN collagenase is a proteolytic enzyme which specifically cleaves native triple helical collagen at physiological pH and temperature. As with other extracellular proteases, there is increasing evidence tha...
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Article
Rigid control of synthesis of collagen Types I and III by cells in culture
THE constituents of the extracellular matrix have a fundamental role in the structure and function of all tissues. A major insight into the composition of this matrix came with the discovery1–3 that interstitial ...
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Article
Fibroblasts degrade newly synthesised collagen within the cell before secretion
COLLAGEN, the major extracellular protein of most tissues, is considered a relatively inert macromolecule, with a turnover rate slower than that of most proteins1. There is, however, a portion of the total collag...
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Chapter
Evaluation of Inflammatory and Immune Processes in the Interstitial Lung Disorders: Use of Bronchoalveolar Lavage
The interstitial lung diseases are a group of chronic, usually fatal disorders that diffusively involve the alveolar structures.1–9 Although there are many types of interstitial diseases, all are characterized by...
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Article
Synthesis in E. coli of α1-antitrypsin variants of therapeutic potential for emphysema and thrombosis
The primary function of α1-antitrypsin (α1-AT), an antiprotease produced by the liver, is the inhibition of neutrophil elastase, a protease capable of hydrolysing most connective tissue components1–4. The importa...
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Article
Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity
Current ideas about the mechanism of wound healing and the pathogenesis of atherosclerosis, pulmonary fibrosis and hepatic fibrosis suggest a central role for the mononuclear phagocyte in attracting and/or sti...
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Article
A Pro → Leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI MHeerlen
The molecular defect has been elucidated in the alpha-1-antitrypsin (PI) gene of a patient with a serum level of only 5 mg/100 ml and a PI M-like phenotype, designated PI MHeerlen. The restriction fragment pat...
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Article
Recombinant Proteins of Therapeutic Interest Expressed by Lymphoid Cell Lines Derived from Transgenic Mice
As a new approach to produce human proteins of therapeutic interest we have derived lymphoid cell lines expressing such proteins from transgenic mice, either by generating trans-hybridomas by cell fusion in vitro
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Article
Strategies for aerosol therapy ofα 1-antitrypsin deficiency by the aerosol route
α1-antitrypsin (AAT) deficiency is a genetic disease in which low serum and lung levels of the antiprotease AAT cause a deficiency of the anti-elastase defensive screen of the lower respiratory tract such that n....
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Article
Altered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation
CYSTIC fibrosis is associated with a defect in epithelial chloride ion transport (reviewed in refs 1, 2) which is caused by mutations in a membrane protein called CFTR (cystic fibrosis transmembrane conductanc...
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Article
Genetic basis of variable exon 9 skip** in cystic fibrosis transmembrane conductance regulator mRNA
Variable in–frame skip** of exon 9 in cystic fibrosis transmembrane conductance regulator (CFTR) mRNA transcripts (exon 9−) occurs in the respiratory epithelium. To explore the genetic basis of this event, we e...
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Article
Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors
To evaluate the potential for adenovirus–mediated central nervous system (CMS) gene transfer, the replication deficient recombinant adenovirus vectors Ad.RSVβgal (coding for β–galactosidase) and Ad–α1AT (codin...
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Article
Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis
We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF). We show that this vector ca...
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Article
The gene as the drug
Caplen et al. (pages 39–46) demonstrate that it is feasible to use liposomes to transfer a human gene in vivo. Can this vector mimic the ability of viruses to effectively transfer genetic information into target ...
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Article
IL-6 release and airway administration of human CFTR cDNA adenovirus vector
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Article
Ectopic expression of thyrotropin releasing hormone (TRH) receptors in liver modulates organ function to regulate blood glucose by TRH
Maintenance of blood glucose by the liver is normally initiated by extracellular regulatory molecules such as glucagon and vasopressin triggering specific hepatocyte receptors to activate the cAMP or phosphoin...
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Article
Managed care for viruses
The finding of a common receptor for coxsackievirus and adenovirus should help improve strategies for drug design and gene therapy.
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Article
Augmentation of blood platelet levels by intratracheal administration of an adenovirus vector encoding human thrombopoietin cDNA
This study was designed to evaluate the hypothesis that administration of a replication-deficient, recombinant adenovirus vector to the epithelial surface of the respiratory tract can be used to deliver a reco...
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Myocardial Angiogenesis: Biology and Therapy
Despite significant advances in its prevention and treatment, coronary artery disease (CAD) remains the leading cause of death in the Western world today. The economic burden of CAD on society is significant. ...
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Article
Use of L-plastin promoter to develop an adenoviral system that confers transgene expression in ovarian cancer cells but not in normal mesothelial cells
The objective of this study was to develop an adenoviral vector system that would generate a pattern of expression of exogenous therapeutic genes appropriate for the treatment of ovarian cancer. For this purpo...