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Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 289 records · Page 16Linked to original sources
PubMed1980

Nucleotide sequence of the E coli gene coding for dihydrofolate reductase.

Plasmid pLC1437a contains DNA from Escherichia coli K12 including fol, the structural gene for dihydrofolate reductase. The fol gene was mapped on this plasmid relative to several restriction endonuclease cleavage sites. fol was also cloned from strain RSO and the nucleotide sequence for the entire fol gene and its flanking regions from this strain was determined. The amino acid sequence predicted from the nucleotide sequence differs in only a few respects from the reported amino acid sequence of dihydrofolate reductase from E. coli B. The major RNA transcripts initiated at the fol promotor in vivo are approximately 550 and 590 nucleotides long. In addition to these, several longer transcripts (up to 1400 nucleotides) are present in lesser amounts. A new procedure is described for 3' end labeling of DNA fragments having blunt ends using E. coli exonuclease III and avian myeloblastoma virus reverse transcriptase.

Base Sequence↗
PubMed1980

Prediction of severity of coronary artery disease using slope of submaximal ST segment/heart rate relationship.

A new exercise electrocardiography test has been examined in patients with angina pectoris; the rate of development of ST segment depression with respect to increases in heart rate during exercise on a bicycle ergometer was measured during exercise using 13 leads in 64 patients. The steepest slope of regression lines relating displacement of ST segment to increases in heart rate (maximal ST/HR slope) was used as an index of myocardial ischaemia and was compared with the results of coronary angiography which were determined by the radiologists and the cardiologist responsible for the management of these patients. The maximal ST/HR slope could be derived consistently from a linear ST/HR relationship (r greater than 0.95) only in 50 patients with significant coronary artery disease (greater than or equal to 75% liminal narrowing). The ranges of the maximal ST/HR slope in 17 patients with single-vessel disease, in 18 patients with double-vessel disease and in 15 patients with triple-vessel disease were different from each other and the differences between the means were statistically significant (P less than 0.0005). The maximal ST/HR slopes for the patients with single-vessel disease were also different from those in the 14 patients in whom significant coronary disease could not be demonstrated. In contrast, the criteria of heart rate at which ST segment depression began, maximum ST segment depression, rate-pressure product and heart rate attained at the end of the test showed an overlap between the groups of the patients studied; using the usual exercise test criteria in the same population, there were three false negative results, one false positive result and the results in eight of the patients were indeterminate. It is concluded that the maximal ST/HR slope, used as an index of myocardial ischaemia, reliably predicted the presence and severity of coronary artery disease, as determined by coronary arteriography in each of the patients with anginal pain.

Adult↗
PubMed1980

Incidence of coronary artery disease in patients with valvular heart disease.

The case notes, cardiac catheterisation data, and coronary arteriograms of 239 patients investigated for valvular heart disease during a five year period were reviewed. Angina present in 13 of 95 patients with isolated mitral valve disease, 43 of 90 patients with isolated aortic valve disease, and 18 of 54 patients with combined mitral and aortic valve disease. Significant coronary artery disease was present in 85 per cent of patients with mitral valve disease and angina, but in only 33 per cent of patients with aortic valve disease and angina. Patients with no chest pain still had a high incidence of coronary artery disease, significant coronary obstruction being present in 22 per cent with mitral valve disease, 22 per cent with aortic valve disease, and 11 per cent with combine mitral and aortic valve disease. Several possible clinical markers of coronary artery disease were examined but none was found to be of practical help. There was, however, a significant inverse relation between severity of coronary artery disease and severity of valve disease in patients with aortic valve disease. Asymptomatic coronary artery disease is not uncommon in patients with valvular heart disease and if it is policy to perform coronary artery bypass grafting in such patients, routine coronary arteriography must be part of the preoperative investigation.

Adult↗
PubMed1979

Regulation of dihydrofolate reductase synthesis in Escherichia coli.

Two clones from the Clarke-Carbon Escherichia coli colony bank were resistant to inhibition by trimethoprim, a potent inhibitor of dihydrofolate reductase. Both clones had elevated levels of dihydrofolate reductase. Furthermore, trimethoprim resistance and elevated enzyme levels were associated with ColE1 plasmids that carried DNA from the trkC ksgA pdxA region of the E. coli chromosome. Plasmid pLC1437a was shown by two criteria to carry the structural gene for dihydrofolate reductase: 1) A partial diploid containing plasmid pLC1437a produced a kinetically-recognizable dihydrofolate reductase that was not present in the parent haploid strain. 2) Plasmid pLC1437a coded for dihydrofolate reductase in vitro. A 1,000 base pair fragment of plasmid pLC1437a containing fol was used as a probe to measure fol mRNA in a mutant strain isolated by Sheldon and Brenner (Molec. gen. Genet. 147, 91-97, 1976). The mutation in this strain, which results in constitutively-high levels of dihydrofolate reductase and in the inability of the strain to grow at 42 degrees C, is cis dominant (Sheldon and Brenner, 1976). The results of kinetic hybridization and pulse-labeling experiments indicated that the regulatory mutant produced elevated levels of dihydrofolate reductase in response to an increased rate of synthesis of fol mRNA.

DNA Restriction Enzymes↗
PubMed1979

Oculomotor nerve regeneration after aneurysm surgery.

A 57-year-old woman had symptoms of oculomotor nerve palsy first appearing one year before successful surgical ligation of a saccular aneurysm arising from the right posterior cerebral artery. During the subsequent postoperative period of two years, oculomotor nerve functions improved as the result of regeneration. Extensive morphometric evaluation of the regenerated nerve was compared to the normal side at the light microscopic level. The affected nerve showed a reduction in the transverse area (62%), estimated number of fibers (49%), and mean diameter of myelinated axons (23%). The normal g-ratio of axon to total diameter was almost constant at 0.64, but on the regenerated side it increased to 0.73. An increase in unmyelinated axons and connective tissue endoneurium was evident at the ultrastructural level. The significance of these marked quantitative changes was compared to the partial return of oculomotor nerve function.

Axons↗
PubMed1979

The major product of PGG2 metabolism by aortic microsomes is 6, 15-dioxo-PGF1 alpha.

Incubations of PGG2 with aortic microsomes yielded two products which were not formed in boiled enzyme control, one of which was 6-oxo-PGF1 alpha. The major metabolite was identified by gas-liquid chromatography-mass spectrometry as 6,15-dioxo-PGF1 alpha. Thus, unlike PGH2, PGG2 is probably converted to 15-hydroperoxy PGI2 which subsequently decomposes to 6, 15-dioxo-PGF1 alpha.

Animals↗
PubMed1979

Preparation and biochemical properties of PGH3.

PGH3 was biosynthesised from all-cis-5,8,11,14,17-eicosapentaenoic acid (20:5 omega 3) by an acetone-pentane powder of ram seminal vesicles and its structure was confirmed by GLC-MS after its reduction to PGF 3 alpha. PGH3 was transformed by horse platelet microsomes to TXB3, and by aortic microsomes to delta 17-6-keto-PGF 1 alpha. The structures of these compounds were confirmed by GLC-MS.

Animals↗
PubMed1979

Restricted lees screen fields in patients with asthenopia, with and without psychogenic disorders.

Lees screen restrictions of non-specific origin, including apparent restrictions of the SR, IR, and LR muscles, were reported last year by Labow et al. In this complementary study, the authors examined eight apparently healthy subjects who had no history of ocular or psychiatric problems, eight psychiatric patients, and eight who had had a CNS disorder or had suffered cerebral trauma. Comparison of the Lees screen findings, visual fields, and accommodative defects of these patients revealed significant restriction of the Lees screen fields in only those patients who had symptoms of asthenopia (including all in the third group). Thus, such restriction does not depend on emotional state.

Adolescent↗
PubMed1979

Mitral annuloplasty--a long term clinical and haemodynamic study.

One hundred and thirteen hospital survivors with mitral annuloplasty have been followed-up from 3--19 years. Actuarially 82.4 +/- 12.1% and 65.1 +/- 18.1% of all patients are expected to be alive at 10 and 19 years respectively. 90.1 +/- 5.9% of patients were predicted to be free from reoperation at 5 years postop, while at 10 and 15 years the figures are 77.2 +/- 13.9% and 53.8 +/- 23.9% respectively. Postoperative haemodynamic investigations, performed in 18 patients at a mean duration of 8.5 (range 4--11) years, showed significant reduction in both mean pulmonary artery and wedge pressures as compared to pre-operative values. 92% of patients were in grade I and II (NYHA) clinically at the latest evaluation as compared to 84% being in grade III and IV pre-operatively. Mitral annuloplasty provides statisfactory long term clinical and haemodynamic improvement in a selected group of patients and should always be considered in the management of mitral regurgitation.

Adolescent↗
PubMed1979

Genitourinary schistosomiasis.

Schistosomiasis is a chronic granulomatous disease endemic in the Middle East and Africa, which undermines the function of the genitourinary tract to a serious degree. It is amenable to medical treatment in the early stages but therapy usually is negated by frequent reinfestations. Patients who have complications in the chronic stage of the disease require the level of judicious handling that always taxes the ingenuity and skill of the urologic surgeon.

Antimony↗
PubMed1978

Further studies on the enzymatic conversion of prostaglandin endoperoxide into prostacyclin by porcine aorta microsomes.

A simple, rapid radiochemical assay for prostacyclin synthesis has been used to characterize the enzyme in arterial walls which converts prostaglandin endoperoxides to prostacyclin. The enzyme displays a broad pH optimum, and catalyses a rapid conversion of saturating concentrations of the endoperoxide at 37 degrees C. Hydroperoxides of several unsaturated fatty acids are potent inhibitors of the enzyme, and act in a time dependent manner. The isomerase which converts prostaglandin endoperoxides to prostaglandin E2 or D2 was not detected in the arterial wall.

Animals↗
PubMed1978

Hemodynamic evaluation of the Ionescu-Shiley pericardial xenograft in the mitral position.

Hemodynamic studies were performed in 27 patients at a mean interval of 40.3 (range 24 to 59) months following mitral valve replacement with pericardial xenografts. Six patients had sequential studies, one before operation and two separate investigations at mean intervals of 11.2 and 42.8 months following valve replacement. The results showed significant increase in cardiac index, reduction in mean pulmonary artery and wedge pressures, and decrease in pulmonary vascular resistance both at rest and during exercise, when compared with the preoperative values. The mean diastolic gradient across the pericardial xenografts was 6.4 mm. Hg at rest and 15.3 mm. Hg during exercise. The calculated xenograft surface area was 2.0 and 2.3 cm.2, respectively. The sequential studies established that the maximum hemodynamic improvement was achieved within the first year following valve replacement and that the functional performance of the xenografts was maintained, unaltered, with the passage of time.

Adult↗
PubMed1978

Hypomagnesaemic hypocalcaemia with hypokalaemia caused by treatment with high dose gentamicin.

A 12-year-old boy developed renal wasting of magnesium, calcium, and potassium, with secondary hypomagnesaemia, hypocalcaemia, and hypokalaaemia (without hyperaldosteronism) after treatment with 14 400 mg gentamicin over 4 months. Gentamicin should not be given for prolonged courses if less toxic antibiotics are suitable. If it used, plasma magnesium, calcium, and potassium levels should be monitored during and after treatment.

Child↗
PubMed1978

Long-term haemodynamic evaluation of aortic pericardial xenograft.

Haemodynamic studies were performed in 30 patients at a mean interval of 43.4 (range 27 to 59) months after aortic valve replacements with pericardial xenografts. Five valve sizes--19, 21, 23, 25, and 27 mm annulus diameter--were used. Of these 30 patients, 16 had preoperative haemodynamic investigations. Comparison of the pre- and postoperative data showed a marginal but significant increase in cardiac output (P less than 0.05). There was a significant reduction in the pulmonary wedge and left ventricular end-diastolic pressures at rest and on exercise (P less than 0.05 and P less than 0.01). At the postoperative study the mean peak systolic gradient was 8.3 mmHg at rest and 12.3 mmHg on exercise in patients with the smallest xenograft inserted (19 mm) and decreased with each corresponding increase in graft size, so that across the 27 mm graft it was hardly measurable. The calculated xenograft surface area ranged from 1.1 to 2.1 cm2 at rest and 1.3 to 2.4 cm2 during exercise. Aortic root angiography showed competent valves in all 30 patients, but a grade 1 to 2 perivalvular leak was shown in 8 patients. This long-term study has indicated significant circulatory improvement and very small transvalvular gradients in patients with aortic pericardial xenografts.

Adult↗