Biomedical subjects

R B Petersen

Publications and source records attributed to R B Petersen.

60 records · Page 4Linked to original sources

PubMed1984

Identification of a ribosome-binding site for a leader peptide encoded by Rous sarcoma virus RNA.

A new method for identifying ribosome-binding sites was developed to determine whether AUG codons in the 5'-terminal RNA sequence of Rous sarcoma virus were used to initiate protein synthesis. We found that when translation is inhibited, the major ribosome-binding site on Rous sarcoma virus RNA is at the 5'-proximal AUG codon, even though the primary translational product from this RNA, Pr76gag, is encoded behind the fourth AUG codon 331 bases downstream from the observed initiation site. These results suggest that ribosomes can initiate translation on Rous sarcoma virus RNA at more than one site, thereby producing a seven-amino-acid peptide, as well as the gag gene polyprotein precursor of Mr 76,000.

Animals↗

PubMed1982

Noninvasive detection and localization of coronary stenoses in patients: comparison of resting dipyridamole and exercise thallium-201 myocardial perfusion imaging.

Two noninvasive tests to detect and localize coronary stenoses were compared in a fully blinded protocol. Thallium201 myocardial perfusion imaging (MPI) following maximal treadmill exercise and pharmacologic coronary vasodilation with intravenous dipyridamole (DP) was performed in 33 patients. Thallium201 imaging defects in six myocardial perfusion regions were correlated with stenoses in their respective vascular distributions. Disease severity was determined with coronary arteriograms using a computer-assisted method. 198 myocardial regions were evaluated; 101 were supplied by at least one major artery with a greater than or equal to 50% stenosis (luminal diameter narrowing). The sensitivity and specificity for detecting a greater than or equal to 50% stenosis were 85% and 64% (p less than 0.005), respectively, for DP and 84% and 68% (p less than 0.005) for exercise-thallium201 imaging. A particular combination of anterior and septal imaging defects was useful in detecting left anterior descending artery stenoses proximal to its first septal branch. DP administration was safe in this group of patients; however, 42% experienced transient chest pain. Although the overall sensitivity and specificity of the two methods were not significantly different, DP-MPI appeared more sensitive than exercise-MPI (70% vs 52%, p less than 0.01) in detecting coronary stenoses in the 40% to 60% range. DP-thallium201 MPI provides a useful alternative test for potential coronary disease patients unable to perform maximal exercise.

Adult↗

PubMed1981

Intravenous dipyridamole combined with isometric handgrip for near maximal acute increase in coronary flow in patients with coronary artery disease.

Twenty-four patients with coronary artery disease were studied during cardiac catheterization to determine the effects of sustained isometric handgrip exercise and intravenous dipyridamole and their combination on coronary and systemic hemodynamics and measured coronary luminal caliber. During 4 to 5 minutes of 25 percent maximal handgrip, blood pressure and heart rate increased 24 and 19 percent, respectively, coronary sinus flow increased to 1.7 x baseline value, and epicardial coronary arteries constricted to increase predicted flow resistance by 40 percent in 36 diseased arterial segments. After a 4 minute intravenous infusion of dipyridamole (0.56 mg/kg body weight), systemic pressure decreased 8 percent, heart rate increased 23 percent, coronary sinus flow increased to 2.4 x baseline value and coronary luminal caliber was unchanged. During isometric handgrip initiated 6 minutes after the infusion of dipyridamole, systemic pressure and heart rate increased to 14 and 31 percent, respectively, above control values, coronary sinus flow increased to 3.3 x baseline value (3.8 x baseline value in patients with normal anterior perfusion) and stenotic flow resistance increased by 36 percent. The response of coronary flow to the combined stresses was 68 percent greater than the response to dipyridamole alone (p less than 0.02); these flow levels exceed values previously reported for the human coronary circulation. Aminophylline plus nitroglycerin appears to assure patient safety.

Acute Disease↗

PubMed1981

The mechanisms of nitroglycerin action: stenosis vasodilatation as a major component of the drug response.

The effect of sublingual or intracoronary nitroglycerin (NTG) on luminal caliber in normal and diseased portions of epicardial coronary arteries was determined in 85 lesions from 57 typical patients with ischemic heart disease. Measurements were made from coronary angiograms, using a computer-assisted method and a carefully blinded protocol for analysis of the pre- and post- NTG angiograms. Luminal area in the "normal" portion of the diseased segment and at its maximum constriction and an estimate of flow resistance in the stenosis were computed. Luminal area increased 1.27 mm2 (p less than 0.001) in the "normal" regions, an average increase of 18% over the control area. Dilation with NTG depended strongly on vessel size; area increased 35% in normal vessels of 1.6-2.3 mm luminal diameter and only 9% in vessels 4.0-5.0 mm in diameter. Lesions were grouped into four levels of severity by percent stenosis. Minimum luminal area increased 0.35 mm2 (p less than 0.01) at the narrowest point in moderate lesions, a 22% area increase, and 0.14 mm2 (p less than 0.001) in severe lesions, a 36% area increase. Stenosis dilation resulted in an average 25% reduction (p less than 0.01) in estimated stenosis flow resistance in moderate lesions and a 38% reduction (p less than 0.001) in severe lesions. A statistically significant resistance reduction of greater than 20% occurred in 15 to 20 severe stenoses; only two of 20 showed no measurable dilation. We reviewed recent literature on hemodynamic responses to NTG and determined that changes of this magnitude are among the largest reported. We conclude that vasodilation of epicardial coronary stenosis is usually a major component of the beneficial response to NTG. We support that conclusion by demonstrating a striking improvement in ischemic left ventricular compliance abnormalities after low-dose intracoronary NTG.

Constriction, Pathologic↗

PubMedDate not supplied

A novel mechanism of phenotypic heterogeneity demonstrated by the effect of a polymorphism on a pathogenic mutation in the PRNP (prion protein gene).

Fatal familial insomnia (FFI) is a subacute dementing illness originally described in 1986. The phenotypic characteristics of this disease include progressive untreatable insomnia, dysautonomia, endocrine and motor disorders, preferential hypometabolism in the thalamus as determined by PET scanning, and selective thalamic atrophy. These characteristics readily distinguish FFI from other previously described neurodegenerative conditions. Recently, FFI was shown to be linked to a mutation in the prion protein gene (PRNP) at codon 178, which results in the substitution of asparagine for aspartic acid. As such, FFI represents the most recent addition to the growing family of prion protein-related diseases. The mutation that results in FFI had previously been linked to a subtype of familial Creutzfeld-Jakob disease (178Asn CJD). The genotypic basis for the difference between FFI and 178AsnCJD lies in a polymorphism at codon 129 of the mutant prion protein gene: 129Met 178Asn results in FFI, 129Val 178Asn in CJD. The finding that the combination of a polymorphism and a single pathogenic mutation result in two distinct conditions represents a significant advance in our understanding of phenotypic variability.

Amino Acid Sequence↗

PubMedDate not supplied

Pathobiology of familial hypercholesterolemic atherosclerosis.

Many factors play a role in the development of atherosclerotic lesions. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia (FH). FH is a genetic disease characterized by a deficiency, and/or mutation, of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells (EC), a high level of low density lipoprotein in the plasma, and early, spontaneous development of atherosclerosis and skin xanthoma. In this review we describe Watanabe heritable hyperlipidemic (WHHL) rabbits, which represent such an animal model for human FH. This strain of the rabbits is characterized by a genetic deficiency or mutation of functional LDL receptors and develops severe atherosclerosis, which is pathologically similar to familial homozygous hyperlipidemic patients. The most completely characterized animal model is the Watanabe rabbit, a model of homozygous and heterozygous type IIa hypercholesterolemia related to an LDL receptor deficiency. Additional manipulation such as aortic injury in this rabbit model induces the development of atherosclerotic lesions that are structurally similar to those found in humans. Thus, this model of hypercholesterolemia fulfils the above criteria set, i.e. it is able to provide new insights for a better understanding of the pathogenesis of atherosclerosis and for testing new treatment strategies.

Animals↗