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Biomedical subjects

R S Fraser

Publications and source records attributed to R S Fraser.

At least 55 records · Page 3Linked to original sources

Long-term survival after isolated replacement of mitral valve with ball-valve prosthesis.

In 111 patients whose diseases mitral valve was replaced with a ball-valve prosthesis the actuarial survival rate, including the hospital mortality of 10.8%, was 66% after 5 years and 59% after 8 years of follow-up. This suggests that in patients with moderate or severe symptoms due to mitral valve disease, replacing the valve can prolong life. However, in patients with no cardiac symptoms or with sinus rhythm and mild symptoms, it is doubtful that mitral valve replacement can prolong life, for the prognosis in these patients is favourable without operation.

Female↗

The roentgenologic diagnosis of chronic bronchitis: a reassessment with emphasis on parahilar bronchi seen end-on.

In an attempt to reassess the accuracy of the roentgenologic diagnosis of chronic bronchitis, we have studied the chest radiographs of approximately 300 men comprising roughly equal numbers of normal subjects and patients with chronic obstructive pulmonary disease (COPD). Emphasis has been placed on the thickness of bronchial walls visualized end-on in the parahilar zones, identified in roughly 80% of both groups. Step-wise discriminant analysis of six variables showed that the median estimate of bronchial wall thickness was of some value in discrimination.

Bronchi↗

Effect of indomethacin and atropine in experimental asthma in conscious guinea pigs.

Pulmonary mechanics were measured in unanesthetized guinea pigs sensitized to horseradish peroxidase (HRP) before and during two aerosolized challenges of this antigen. During the first challenge the pulmonary resistance increased in all animals. Prior to second challenge the animals received either atropine (0.2 mg/kg) or indomethacin (10 mg/kg) intraperitoneally. We found that during the second challenge the indomethacin group had an increase in pulmonary resistance slightly greater or similar to that during the first exposure to the antigen, while the animals treated with atropine had a significantly diminished response (P less than 0.05). In five guinea pigs sensitized to HRP but challenged with a nonspecific aerosal made up of rabbit albumin, we found that pulmonary resistance increased in some animals and that this increase could be partially blocked by atropine. These results show that indomethacin has no effect on this model of allergic airways disease. They also confirm the importance of the vagus nerves in allergic bronchoconstriction and in addition show that nonspecific hyperirritability can be induced in some animals by immunization.

Aerosols↗

Rates of synthesis of polyadenylated messenger RNA and ribosomal RNA during the cell cycle of Schizosaccharomyces pombe. With an appendix: calculation of the pattern of protein accumulation from observed changes in the rate of messenger RNA synthesis.

The rates of polyadenylated messenger RNA and ribosomal RNA synthesis were measured in synchronously dividing cultures of fission yeast (Schizosaccharomyces pombe). Control asynchronous cultures, which had been exposed to the conditions used for preparing synchronous cultures, were investigated to check for effects of the synchronization procedure itself on RNA synthesis. After each period of DNA synthesis in synchronous culture, the rates of messenger and ribosomal RNA synthesis doubled, suggesting that gene number controls the rate of messenger and ribosomal RNA synthesis. This was confirmed by experiments with asynchronous, exponential-phase cultures in which DNA synthesis was inhibited by hydroxyurea. Both synchronous culture and hydroxyurea experiments suggested that there is a delay of 15 min (0-1 of the cell generation time) between replication of the DNA and transcription of both gene copies. A pattern of protein accumulation was calculated from changes in the rate of polyadenylated messenger RNA synthesis during synchronous culture. The simulated pattern indicates that protein is accumulated linearly, with a doubling in the rate of accumulation once per cell cycle. The simulated pattern of protein accumulation is very similar to measurements previously reported by other workers of changes in activities of 3 enzymes in synchronous cultures. It is suggested that the doubling of the rate of messenger RNA synthesis, as a consequence of the replication of the DNA once per cycle, provides the basis of a mechanism for control of the doubling of other cellular constituents during the cell cycle.

Adenine↗

The assessment of function of left ventricle and patency of aorta-coronary bypass after operation. A study of systolic time intervals.

The effect of aorta-coronary bypass surgery on left ventricular function was evaluated in 39 patients by cardiac catheterization and recording of the systolic time intervals (STI) before and an average of 4.5 months following myocardial revascularization. All patients were in sinus rhythm, had normal QRS intervals on the electrocardiogram, and had taken no medication for at least 3 weeks prior to the study. The STI was unchanged postoperatively in patients with the following characteristics: freedom from angina; heart rate not more than 15 beats greater than the preoperative level; all grafts patent; and no progression of disease in coronary arteries. Deterioration in left ventricular function after operation as represented by shortened left ventricular ejection time, (LVET) prolonged pre-ejection period (PEP), and increased ratio of PEP/LVET was found in patients with the following characteristics: persistent angina; heart rate more than 14 beats faster than the preoperative level; occlusion of any grafts; progression of disease in the coronary arteries; evidence for postoperative myocardial infarction. Worsening of left ventricular performance as determined by STI was more apparent in patients with occluded grafts and no collateral circulation than in those with occluded grafts and collateral circulation which may have offered protection against ischemia. These investigations supported the use of STI in assessing changes in left ventricular function after coronary bypass and, by inference, in assessing the status of the graft.

Adult↗

Turnover of polyadenylated messenger RNA in fission yeast. Evidence for the control of protein synthesis at the translational level.

Polyadenylated RNA was isolated from fission yeast (Schizosaccharomyces pombe) total RNA using oligo(dT)-cellulose, and was studied as a model for messenger RNA. The half-life of poly adenylated RNA was measured by two independent methods. (a) The rate of labelling of polyadenylated RNA during incubation of cells with [5-3H]uridine was measured. A half-life of 40-45 min was found by comparing the experimental data with theoretical curves calculated for labelling of RNAs with various half-lives. The influence of precursor-pool specific activity on RNA labelling kinetics is considered. (b) Cells were labelled with [5-3H]uridine then further RNA synthesis was inhibited by addition of 8-hydroxyquinoline. The rate of loos of radioactivity from polyadenylated RNA indicated a half-life of 50 min. The half-life found by these two methods is about one-third of the cell doubling time, and is much longer than previous estimates by indirect methods of yeast messenger RNA half-life. Both experimental methods provided evidence for the existence of tas a half-life of 40-50 min; a much smaller population is probably turning over more rapidly. After inhibition of RNA synthesis by 8-hydroxyquinoline, the rate of total protein synthesis declined much more rapidly than the polyadenylated RNA content of the cells. However, 60 min after inhibition of RNA synthesis there was a small rise in the rate of portein synthesis. These data are interpreted as evidence for mechanisms controlling protein synthesis which operate at the level of messenger RNA translation.

Ascomycota↗

Studies on messenger and ribosomal RNA synthesis in plant tissue cultures induced to undergo synchronus cell division.

Messenger and ribosomal RNA metabolism was tudied in a plant tissue culture system: cells from the quiescent tubers of Helianthus tuberosus (Jerusalem artichoke) were induced to divide synchronously and dedeifferentiate by excision and culture of explants in nutrient medium. Large accumulations of ribosomal RNA and protein started early in the 20-h lag-period preceding the first division. In pulse-labelling experiments, two types of polydisperse messenger-like RNAs were detected one with and one without a poly(adenylic acid) sequence. In the first 2 h of culture the two polydisperse RNA fractions were the predominant types of RNA synthesised. Ribosomal RNA synthesis was very low during the first 2 h, but acclerated later. Low concentrations of actinomycin-D strongly inhibited ribosomal RNA synthesis, but had little effect on the synthesis of transfer RNA or either type of polydisperse messenger-like RNA. In explants cultured with low concentrations of actinomycin-D ribosomal RNA accumulation was completely inhibited, but cell division and protein accumulation occurred, though at a reduced rate. It is concluded that the synthesis and accumulation of new ribosomal RNA which normally occur during culture are not required for the induction of cell division or for protein accumulation, i.e. the ribosomal RNA existing in the quiescent tuver cells can support protein accumulation and cell division induced by excision and culture. The quiescent tuber tissue is also shown to contain significant amounts of messenger-like RNA.

Cell Division↗

The mechanism of inhibition of ribonucleic acid synthesis by 8-hydroxyquinoline and the antibiotic lomofungin.

RNA synthesis in yeast is rapidly inhibited by 8-hydroxyquinoline and the phenazine antibiotic lomofungin (5-formyl-1-methoxycarbonyl-4,6,8-trihydroxyphenazine). It is shown that lomofungin, like 8-hydroxyquinoline, is a chelating agent for bivalent cations. The mechanism of inhibition of RNA synthesis by lomofungin and 8-hydroxyquinoline was investigated in experiments with isolated Escherichia coli RNA polymerase. The results show that both inhibitors are capable of inhibiting polymerase activity solely by chelating the dissociable cations Mn2+ and Mg2+. Evidence is presented which shows that inhibition may occur in the absence of any direct contact between the RNA polymerase or DNA template and the inhibitor. The possibility that inhibition might also occur by chelation of the Zn2+, which is tightly bound to the polymerase, is discussed: it is concluded that lomofungin or 8-hydroxyquinoline is likely to inhibit the enzyme by removal of Mn2+ and Mg2+ before chelating the Zn2+. On the basis of inhibition by chelation of Mn2+ and Mg2+, explanations are proposed for why lomofungin and 8-hydroxyquinoline inhibit synthesis of ribosomal and polydisperse RNA more than that of 5S RNA and tRNA, and for why protein synthesis is not immediately inhibited in the intact yeast cell.

Chelating Agents↗

Ruptured aneurysms of sinuses of Valsalva.

At least one additional cardiac lesion was present in 18 consecutive patients with ruptured aneurysms of the sinuses of Valsalva who were investigated between 1956 and 1973 at the University of Alberta Hospital. Clinical diagnosis was made in 78% (14/18) of the patients. Confirmation at cardiac catheterization, operation or autopsy was obtained in all but one. The main sites of rupture were the right ventricle (seven cases), right atrium (five) and left ventricle (five). Fifty percent (9/18) are alive and well following prompt operative repair, an average of 8.2 years later (range, six months to 15 years). Replacement of the aortic valve was associated with a high mortality (50% early, 13% late, total 63%) which could be explained by the higher operative risk in this group of very ill patients. Eight patients (44.4%) had had bacterial endocarditis prior to presentation and this may have played a significant role in the rupture of the sinus of Valsalva aneurysm.

Adolescent↗