Biomedical subjects

J B Lowe

Publications and source records attributed to J B Lowe.

At least 163 records · Page 9Linked to original sources

PubMed1983

Mechanism of F factor-enhanced excision of transposon Tn5.

The reversion of lac:: Tn5 insertion mutations was used to examine the control of excision of the kanamycin-resistance transposon Tn5 in Escherichia coli. Earlier work which showed that the fertility factor F enhances Tn5 excision had led another group to suggest that this is due to the product of a putative transposable element-specific "recombination" gene in the F factor which can act on Tn5 located anywhere in the genome. We show, however, that Tn5 is excised from sites in the lac operon of F'lac plasmids several orders of magnitude more efficiently than from the same sites in the chromosomes of F-, F+ or homozygous lac:: Tn5[F'lac:: Tn5] strains. Thus F enhances Tn5 excision, but only if F and Tn5 are in cis in the same DNA molecule. Bacterial crosses showed that transfer of F'lac:: Tn5 plasmids by conjugation stimulates Tn5 excision, and that transfer is frequent even within F' populations. These results suggest that the ability of F to enhance excision is the consequence of DNA transfer in conjugation.

Conjugation, Genetic↗

PubMed1983

A product of the TN5 transposase gene inhibits transposition.

The bacterial transposon Tn5 possesses a regulatory mechanism that allows it to move with higher efficiency when it is first introduced into a cell than after it is established. Tn5 is a composite transposable element containing inverted repeats of two nearly identical elements, IS50R, which encodes the transposase protein necessary for Tn5 movement, and IS50L which contains an ochre mutant allele of the transposase gene. Data presented here show that Tn5 transposition is inhibited about 50-fold in cells of Escherichia coli which already carry IS50R in the multicopy plasmid pBR322. If the cells contain a plasmid carrying either IS50L instead of IS50R, or derivatives of IS50R in which the transposase gene has been mutated, little if any inhibition of Tn5 transposition is found. Although inhibition had previously been hypothesized to require interaction between the products of IS50L and IS50R, our results show that IS50R alone is sufficient to mediate inhibition and suggest that the inhibitor is a product of the transposase gene itself.

Bacteriophage lambda↗

PubMed1983

Specificity of transposon Tn5 insertion.

Genetic mapping studies had shown that the bacterial transposon Tn5 can insert into many sites in a gene, but that some sites are preferred. To begin understanding Tn5's insertion specificity at the molecular level, we selected transpositions of Tn5 from the Escherichia coli chromosome to the plasmid pBR322 and analyzed the resultant pBR322::Tn5 plasmids by restriction endonuclease digestion and DNA sequencing. Seventy-five insertions in the tet gene were found at 28 sites including one major hotspot (with 21 insertions) and four lesser hotspots (with four to ten insertions each). All five hotspots are within the first 300 of the 1250-base pair (bp) tet gene. In contrast, 31 independent insertions in the amp gene were found in at least 27 distinct sites.--Tn5 generates 9 bp target sequence duplications when it transposes. Such transposon-induced duplications are generally taken to indicate that cleavages of complementary target DNA strands are made 9 bp apart during transposition. DNA sequence analysis indicated that GC base pairs occupy positions 1 and 9 in the duplications at each of the five hotspots examined, suggesting a GC-cutting preference during Tn5 transposition.

Base Sequence↗

PubMed1982

Infective endocarditis: prudent treatment for a lethal disease.

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Drug Therapy, Combination↗

PubMed1982

Control of transposon Tn5 transposition in Escherichia coli.

Tn5 is a composite transposable element in which the insertion sequences IS50R and IS50L bracket a central region encoding kanamycin resistance (kanr). IS50R encodes a functional transposase, whereas IS50L contains the promoter of the kanr gene. To determine the relative activities of IS50R and IS50L in transposition we examined the structures of chimeric DNA molecules generated by insertion of segments of pBR322::Tn5 dimeric plasmids into red- lambda phage in recA- Escherichia coli. Restriction endonuclease analyses showed that the inserted sequences contained direct terminal repeats of pairs of IS50R or of IS50L elements and that the frequencies of usage of IS50R vs. IS50L depended on the position and orientation of Tn5 in the plasmid vector: IS50R was used preferentially when Tn5 was in transcriptionally quiescent regions of the vector (in either orientation) or when IS50L was immediately downstream from a strong promoter in the vector. In contrast, IS50L was used preferentially when IS50R was downstream from a strong promoter. We conclude IS50R tends to be used preferentially but that when transcription impinges on the end of an IS50 element the participation of that element in transposition is inhibited.

Base Sequence↗

PubMed1981

Amiodarone in long term management of refractory cardiac tachyarrhythmias.

Amiodarone was used in 30 patients with tachyarrhythmias refractory to treatment with several antiarrhythmic agents. In 18 patients with supraventricular arrhythmias (recurrent atrial tachycardia in seven; atrial fibrillation, recurrent in four and persistent in five; Wolff-Parkinson-White syndrome in two), complete control was obtained in eight and marked improvement in eight patients. Conversion of persistent atrial fibrillation to sinus rhythm was documented in three patients. Congestive heart failure improved markedly in three patients who had persistent atrial fibrillation during amiodarone therapy. In 12 patients with tachycardia of ventricular origin effective control was obtained in nine. The incidence of side effects was low. Amiodarone is effective in maintaining sinus rhythm in many patients with both supraventricular and ventricular tachyarrhythmias when standard antiarrhythmic agents have failed.

Adult↗

PubMed1981

Infective endocarditis: a lethal disease.

One-hundred-and-eighty-nine episodes of infective Endocarditis were seen in 177 patients in the Green Lane Cardiology Unit over a 18-year period. Hospital survival was 79% and 13-year actuarial survival was 47%. A number of factors including the underlying cardiac lesion, infecting organism, clinical features and surgical intervention were related to outcome. No patient with extreme heart failure survived without operation. Hospital survival in patients with severe heart failure was 69% (9/13 patients) where surgery was carried out before completion of antibiotic treatment, and 40% (6/15 patients) where the antibiotic course was completed. Survival was 53% in patients who still had a fever after one week of antibiotic treatment and 96% if the temperature was normal. In 61% of patients with a fever at one week, extended infected pannus was present compared with 6--10% where the temperature was normal. In patients undergoing operation before completion of antibiotics, the surgical mortality was higher but neither the incidence of recurrence of endocarditis nor the need for re-operation was increased. We believe that better results will be achieved with a policy of surgical intervention when signs of infection and heart failure have not settled within one week of treatment.

Actuarial Analysis↗

PubMed1981

Coronary surgery after recurrent myocardial infarction: progress of a trial comparing surgical with nonsurgical management for asymptomatic patients with advanced coronary disease.

A randomized trial of surgical vs nonsurgical management was carried out in men 60 years of age or younger who had recovered from a recurrent myocardial infarction. Of 205 patients considered, 100 had few or no symptoms and had coronary vessels favorable for bypass grafting; these patients fulfilled the trial conditions and were randomized (50 surgical and 50 nonsurgical). In 41 patients (elective nonsurgical group), randomization was not considered justifiable because of relatively unfavorable coronary anatomy or severe left ventricular dysfunction. Nineteen patients had elective surgery because of disabling angina despite full medical treatment or because of significant left main coronary stenosis. In 45 patients, coronary angiography was not undertaken because of medical contraindications or reluctance of the patient to enter the study. Actuarial survival curves (mean follow-up 4.5 years) show an annual mortality rate of 3-4% per year for all investigated patients, and no advantage for the randomized surgical over the randomized nonsurgical group. The results suggest that in the absence of disabling angina or left main coronary artery stenosis, coronary artery surgery need not be advised for survivors of recurrent infarctions who have severe coronary artery disease. Moreover, the prognosis for the group of patients not treated surgically appears to be better than has been previously described.

Adult↗

PubMed1981

Open mitral valvotomy. Effect of preoperative factors on result.

On hundred fifty-four patients who underwent open mitral valvotomy in the years of 1968 to 1976 were reviewed 1 to 112 months (mean 48) postoperatively. There was one hospital death and there were 14 late deaths (nine cardiac), and 16 patients required reoperation during the follow-up period. Preoperative factors were examined to assess their association with an unsatisfactory postoperative course. End points included unsatisfactory symptomatic status, the need for reoperation, and postoperative death. Maori race and atrial fibrillation (AF) were associated with all three end points. Other preoperative factors associated with at least one unfavorable end point were female sex, unfavorable preoperative symptomatic status, the presence of mild associated mitral incompetence (MI), a previous operation, and the presence of calcification in the mitral valve. The degree of subvalvular fusion and the adequacy of valvotomy assessed at operation were also related to outcome. A binary regression program was developed to assist in the prediction of outcome from an assessment of preoperative factors. Preoperative embolism occurred in 31 patients and postoperative embolism in 13. Postoperative embolism occurred in 35% of patients with a preoperative embolic episode and AF. Open mitral valvotomy carries a low operative risk, but unfavorable preoperative factors militate against a satisfactory long-term result and protection from recurrent embolism is only partial.

Adolescent↗

PubMed1980

Congenital valvar aortic stenosis. Natural history and assessment for operation.

Two hundred and eighteen patients with congenital valvar aortic stenosis aged between 1 and 25 years at presentation were followed for one to 26 years (average 8.7 years). Assessment of severity of aortic stenosis was essentially based on clinical findings including symptoms, the character of the pulse, and the behaviour of the second heart sound, management being further influenced by the degree of left ventricular hypertrophy shown in the electrocardiogram. There was reasonable correlation between clinical and haemodynamic assessment and all patients with a gradient between left ventricle and aorta (LV-Ao) greater than 50 mmHg (6.7 kPa) were judged to have moderate or severe aortic stenosis on physical signs. Fifty-five per cent of those judged mild on presentation still had a mild lesion 18 years later; 42 per cent of those judged moderate on presentation still had a moderate lesion 15 years later. Forty-four patients had an operation and of the 30 patients who underwent aortic valvotomy, only 40 per cent still had a satisfactory result 13 years later. There were three preoperative and seven postoperative deaths but in only two patients was death directly related to severe aortic stenosis and both of these patients had been lost to follow-up. It is concluded that indications for operation are aortic stenosis which is moderate or severe on physical findings, together with restrictive symptoms or ST and T wave changes on the electrocardiogram. Using these criteria, the risk of sudden death is minimal and irreversible myocardial damage unlikely. We do not recommend either routine cardiac catheterisation or routine operation at any arbitrary LV-Ao gradient.

Adolescent↗

PubMed1977

Surgical resection in idiopathic hypertrophic subaortic stenosis with a combined approach through aorta and left ventricle.

The operative technique and the immediate and long-term results are described in 49 patients who have undergone myectomy for IHSS. There was a 4 percent early and 12 percent late mortality rate and surviving patients have been followed for up to 13 years. The operation has resulted in a striking symptomatic improvement in most patients in association with relief of outflow obstruction and mitral regurgitation. Chronic atrial fibrillation was poorly tolerated but has not occurred as a late complication in any of the patients operated upon.

Adolescent↗

PubMed1973