The main purpose of animal models for proliferative vitreoretinopathy (PVR) is to develop pharmacologic therapies for this common cause of blindness. A very large number of pharmacologic agents appear to have potential use in this application by preventing cell proliferation and/or contraction. In practice, however, it has been found that prohibitively extensive numbers of animals and laboratory services are required to establish drug efficacy, safety, and dosage regimes. To lessen this work load and to accelerate drug screening programs, the authors have developed an in vitro model for PVR based on chorioretinal fibroblast growth in three-dimensional collagen lattices. This model yields precise data on the effect of drugs on cell proliferation and contractility. Trifluoperazine, colchicine, 5-fluorouracil, dexamethasone. and penicillamine were screened in this model. The first three agents were found to be inhibitory; on the basis of the pharmacokinetic data, obtained dosage regimes for animal testing were developed. The results obtained are discussed in terms of the in vitromodel and the biochemical action of these drugs on the cellular events in PVR. In vitroscreening of drugs prior to animal testing offers a significant advance in the quest for a pharmacologic prevention of blindness due to PVR. RETINA 5:239-252, 1985
The main purpose of animal models for proliferative vitreoretinopathy (PVR) is to develop pharmacologic therapies for this common cause of blindness. A very large number of pharmacologic agents appear to have potential use in this application by preventing cell proliferation and/or contraction. In practice, however, it has been found that prohibitively extensive numbers of animals and laboratory services are required to establish drug efficacy, safety, and dosage regimes. To lessen this work load and to accelerate drug screening programs, the authors have developed an in vitro model for PVR based on chorioretinal fibroblast growth in three-dimensional collagen lattices. This model yields precise data on the effect of drugs on cell proliferation and contractility. Trifluoperazine, colchicine, 5-fluorouracil, dexamethasone, and penicillamine were screened in this model. Thefirst three agents were found to be inhibitory; on the basis of the pharmacokinetic data, obtained dosage regimes for animal testing were developed. The results obtained are discussed in terms of the in vitro model and the biochemical action of these drugs on the cellular events in PVR. In vitro screening of drugs prior to animal testing offers a significant advance in the quest for a pharmacologic prevention of blindness due to PVR.
Background Recently, we localized the Human Poliovirus Receptor Related 2 Gene (PRR2) 17kb centromeric to the gene for apolipoprotein E (APOE). Common polymorphisms in the latter have been found, in some studies, to be related to coronary heart disease (CHD) but the PRR2 gene has not been studied in this context. Here, we examined relationships between a PRR2 Sau96I (A/G) polymorphism, the ∊2, 3 and 4 alleles of APOE and CHD. Design and methods Consecutive Caucasian patients (n=640) < 50 years with angiographically documented coronary obstructive disease and/or with unequivocal myocardial infarction were compared with 624 control subjects, aged 30–50 years, randomly selected from the community and without a history of CHD. Results An excess of PRR2-A homozygotes was observed in cases (20% vs. 15%; OR 1.4, CI 1.04–1.86, P=0.026) particularly in those with single vessel disease (OR 1.7, CI 1.2–2.4, P<0.01). The A allele was in linkage disequilibrium with the ∊4 allele and the G allele with the ∊2. Overrepresentation of the A allele and underrepresentation of the G allele in the CHD group did not reach significance (P=0.054). While the ∊2 allele was under-represented in the CHD group (OR 0.64, CI 0.46–0.89, P=0.009), the ∊4 allele was not significantly overrepresented. Conclusion The relationship between the PRR2 Sau96I (A/G) polymorphism and early onset coronary artery disease may be due to linkage disequilibrium with the APOE gene and underrepresentation, or a protective effect, of the ∊2 allele. Alternatively, since A allele homozygosity is particularly overrepresented, the relationship could be more direct, perhaps through a viral association.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransferrins - Illustrative metal-binding proteinsJ. Web and F. M. van Bockxmeer Cite this: J. Chem. Educ. 1980, 57, 9, 639Publication Date (Print):September 1, 1980Publication History Received3 August 2009Published online1 September 1980Published inissue 1 September 1980https://doi.org/10.1021/ed057p639RIGHTS & PERMISSIONSArticle Views88Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1011 KB) Get e-Alerts Get e-Alerts
Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was ∼30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxyl-terminal 12% of the mature LPL. Trp 394 is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 ± 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 ± 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.
A procedure for desensitising natural arterial actomyosin by precipitation at 1=0.22 is described. The desensitised arterial actomyosin superprecipitated in the absence of Ca2+ and its Mg2+-activated adenosine triphosphatase [EC 3. 6. 1. 3] was increased 7 fold suggesting an inhibitor had been removed. When the soluble protein fraction which had been removed from the natural arterial actomyosin at 1=0.22 was replaced, superprecipitation and the Mg2+-activated adenosine triphosphatase activity were inhibited. Skeletal troponin complex was also found to be a potent inhibitor of this desensitised arterial actomyosin, but skeletal and arterial tropomyosin were without effect. Polyacrylamide gel electrophoresis showed that tropomyosin was the chief relaxing protein in the soluble arterial protein fraction, together with a low proportion of protein of a similar electrophoretic mobility to that of skeletal troponin complex. Arterial tropomyosin was functionally and electrophoretically identical to skeletal tropomyosin. It is concluded that a relaxing protein system exists in vascular smooth muscle which functions similarly to that in striated muscle.
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