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D A Morrison

Publications and source records attributed to D A Morrison.

At least 73 records · Page 4Linked to original sources
PubMed1996

Competence for genetic transformation in encapsulated strains of Streptococcus pneumoniae: two allelic variants of the peptide pheromone.

The nucleotide sequence of comC, the gene encoding the 17-residue competence-stimulating peptide (CSP) of Streptococcus pneumoniae (L. S. Havarstein, G. Coomaraswamy, and D. A. Morrison, Proc. Natl. Acad. Sci. USA 92:11140-11144, 1995) was determined with 42 encapsulated strains of different serotypes. A new allele, comC2, was found in 13 strains, including the type 3 Avery strain, A66, while all others carried a gene (now termed comC1) identical to that originally described for strain Rx1. The predicted mature product of comC2 is also a heptadecapeptide but differs from that of comC1 at eight residues. Both CSP-1 and CSP-2 synthetic peptides were used to induce competence in the 42 strains; 48% of the strains became competent after the addition of the synthetic peptide, whereas none were transformable without the added peptides.

Alleles↗
PubMed1995

An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae.

Competence for genetic transformation in Streptococcus pneumoniae has been known for three decades to arise in growing cultures at a critical cell density, in response to a secreted protease-sensitive signal. We show that strain CP1200 produces a 17-residue peptide that induces cells of the species to develop competence. The sequence of the peptide was found to be H-Glu-Met-Arg-Leu-Ser-Lys-Phe-Phe-Arg-Asp-Phe-Ile-Leu-Gln-Arg- Lys-Lys-OH. A synthetic peptide of the same sequence was shown to be biologically active in small quantities and to extend the range of conditions suitable for development of competence. Cognate codons in the pneumococcal chromosome indicate that the peptide is made ribosomally. As the gene encodes a prepeptide containing the Gly-Gly consensus processing site found in peptide bacteriocins, the peptide is likely to be exported by a specialized ATP-binding cassette transport protein as is characteristic of these bacteriocins. The hypothesis is presented that this transport protein is encoded by comA, previously shown to be required for elaboration of the pneumococcal competence activator.

Amino Acid Sequence↗
PubMed1995

Construction and evaluation of new drug-resistance cassettes for gene disruption mutagenesis in Streptococcus pneumoniae, using an ami test platform.

Although drug-resistance markers have been used frequently for gene-disruption mutagenesis in Streptococcus pneumoniae, none has yet been shown to be free of dependence on local transcription for its expression. Indeed, the erythromycin-resistance marker (erm), originating in pAM beta 1, has been used as an indicator of local transcription on several occasions. A procedure is demonstrated for evaluation of the autonomous expression of such a marker by placing it in a consistent background, at the pneumococcal ami (aminopterin resistance) locus, in combination with active or inactive alleles of the ami promotor (pA). Using this test platform, a chloramphenicol-resistance marker (cat) and a spectinomycin-resistance marker used in streptococcal gene disruption studies and derived from pJS3 and pDL269, respectively, were shown to depend on local transcriptional signals for expression when placed in the pneumococcal chromosome as single-copy genes. To overcome this limitation, new drug-resistance cassettes were designed and constructed, using pA as a model for synthetic promoters for the erm and cat genes. Both new cassettes were shown, by the same procedure, to be expressed after insertion in the pneumococcal chromosome, independent of local transcription. A new insertion-duplication vector, pEVP3, incorporating the new cat cassette and a lacZ reporter derived from pTV32, was also constructed. The ami test platform was used to demonstrate both the autonomous expression of cat and the reporter function of lacZ in chromosomal copies of pEVP3.

Amino Acid Sequence↗
PubMed1995

Competence for genetic transformation in Streptococcus pneumoniae: organization of a regulatory locus with homology to two lactococcin A secretion genes.

Regulation of competence for genetic transformation in Streptococcus pneumoniae involves the comAB locus and a small extracellular protein, the competence factor (CF). The comA or comB mutations block both spontaneous competence induction and elaboration of CF, yet permit induction of competence by added CF and subsequent transformation at normal levels. Sequence and genetic studies showed that the com locus comprised the comA and comB genes, encoding 77- and 50-kDa proteins, respectively, and demonstrated that they were closely flanked by genes and DNA not required for competence regulation. In-frame deletion of comA demonstrated that the translation product of this gene is required for normal competence regulation; deletion-replacement mutations showed that no com gene lay in the 0.2-kb gap between comB and purC or within 2.5 kb upstream from comA. Strong sequence similarities (51-59% identities) showed that ComA and the proteins, PdcD and LcnC, which act in the secretion of pediocin A-1 and lactococcin A, respectively, form a subfamily within the large ABC-transporter protein family. ComB was found to be homologous to a single known protein, LcnD, required for secretion of the peptide antibiotic lactococcin A. Thus, the comAB locus displays homology to two lactococcin A secretion genes, but is devoid of additional linked com genes. The results suggest that the mechanism for CF production is similar to that for the small peptide bacteriocins, lactococcin A and pediocin A-1, but that its genetic organization is unusual in being split into at least two separate operons.

ATP-Binding Cassette Transporters↗
PubMed1995

Effectiveness of percutaneous transluminal coronary angioplasty for patients with medically refractory rest angina pectoris and high risk of adverse outcomes with coronary artery bypass grafting.

This study was undertaken to test the hypothesis that percutaneous transluminal coronary angioplasty (PTCA) is a reasonable alternative to coronary artery bypass grafting (CABG) for some high-risk patients with medically refractory rest angina. Over a 5-year period, 1 operator at a tertiary Veterans Affairs Medical Center performed angioplasty on 624 patients, of whom 441 had unstable angina. Of these 441 patients, 288 had rest angina and 225 had medically refractory rest angina. Medically refractory unstable angina was defined as reversible myocardial ischemia occurring at rest in an intensive care unit setting with low flow oxygen despite the following medications: (1) oral aspirin, intravenous heparin, or both; (2) some combination of beta blocker, calcium blocker, and/or nitrate so that resting heart rate is < 70 beats/min or resting blood pressure < 140 mm Hg, or both. There were 207 patients with medically refractory rest angina who had > or = 1 of the following characteristics predictive of a more than twofold increased risk of operative death at CABG: age > 70 years, prior CABG, recent myocardial infarct, need for intravenous nitroglycerin, need for intraaortic balloon pump, and left ventricular ejection fraction < 0.35. Of these 207 patients, 11 died (5%) during index hospitalization, 196 (95%) were discharged, and 186 (90%) went home angina free. There were 2 emergency CABGs and 9 acute myocardial infarctions. At follow-up (3 to 60 months, average 24), there were 27 late deaths (for a total of 38 [18%]), 8 (4%) late CABGs, and 44 (21%) late PTCAs (with 17 [8%] late myocardial infarctions). The 2-year mortality of 18% for this cohort is comparable to a 21% 2-year mortality observed in a group of 1,073 "high-risk" patients who underwent CABG in the Veterans Affairs Medical Center from 1987 to 1988. These data support the hypothesis that PTCA provides an alternative to CABG in some high-risk patients with medically refractory rest angina.

Age Factors↗
PubMed1995

Characterization of IS1167, a new insertion sequence in Streptococcus pneumoniae.

A new insertion sequence in Streptococcus pneumoniae was identified as a 1435-bp segment of the genome containing 24-bp terminal inverted repeats and flanked by 8-bp direct repeats. A copy of the element, named IS1167, adjacent to the comAB genes was sequenced; seven additional copies were found in the genome of strain CP1200 and relatives descended from strain R36A. Among 22 independent pneumococcal isolates, 11 contained copies of elements hybridizing to IS1167 in nine distinct restriction fragment patterns, with 3-12 copies each. The bulk of the element was occupied by two overlapping open reading frames, encoding basic proteins which together exhibited strong similarity to the full length of the putative transposase of the staphylococcal transposable element, IS1181, as well as significant similarity to those of seven additional known or putative insertion sequences related to the mycobacterial element, IS1096.

Amino Acid Sequence↗
PubMed1995

Comparison of the patterns of codon usage and bias between Brugia, Echinococcus, Onchocerca and Schistosoma species.

Patterns of codon usage and bias were compared among taxa of the genera Brugia, Echinococcus, Onchocerca and Schistosoma by metric multidimensional scaling and three commonly used indices of bias: Nc, GC3S and B. The overall codon usage for each taxon was compared, as was the codon usage for each individual gene within the taxa. Differences in the patterns of codon usage observed between taxa were dependent on the overall base composition of the genes analysed. The codon usage of Echinococcus was distinct from that of the other taxa. Furthermore, the pattern of codon usage detected by the average codon usage summed across all genes for each taxon was not shown by all genes from that taxon.

Animals↗
PubMed1995

Schistosoma mansoni: patterns of codon usage and bias.

Codon usage and bias has been examined in 20 genes of Schistosoma mansoni. Significant heterogeneity was detected in the patterns of codon usage and bias among genes by metric multidimensional scaling and three general indicators of bias (GC3S, Nc and B). In keeping with observations on sporozoan parasites, codon usage bias was observed to be dependent on the overall base composition of the genes analysed, which in turn was reflected in the types of codons that were over or under-represented in the sequences.

Animals↗
PubMed1994

Percutaneous transluminal coronary angioplasty of the left main coronary artery in patients with rest angina.

Left main coronary angioplasty may be a therapeutic revascularization procedure for a subset of patients with symptomatic coronary artery disease. The purpose of this study is to report procedural outcomes and long-term clinical follow-up of 15 patients who underwent either protected or unprotected left main angioplasty for rest angina. These patients represent a cohort of unstable angina patients who were considered high risk for coronary artery bypass surgery. Ten of 15 patients had Canadian Heart Class IV angina, and three patients were hemodynamically unstable. Balloon angioplasty was successful in 4 patients, and one patient was treated with directional atherectomy. Initial angiographic success was achieved in 14 of 15 patients (93%). Major complications (myocardial infarction, emergent coronary artery bypass graft, death) occurred in one patient (6%); 73% of the patients were asymptomatic or had stable exertional angina at 6 months follow-up. One year survival was 87% (13 of 15). During the follow-up period six patients had repeat catheterization for recurrent angina. Four of these patients had left main restenosis and underwent successful repeat left main angioplasty. No patient had coronary bypass surgery during follow-up. This report suggests that left main angioplasty can be a safe and effective revascularization procedure for critically ill patients with unstable angina who are at high risk for coronary bypass surgery.

Aged↗
PubMed1994

An empirical comparison of distance matrix techniques for estimating codon usage divergence.

The quantitative description of codon usage divergence among taxa is a two-step process involving first the calculation of a standardized measure of intertaxon divergence for each possible pair of taxa followed by a summary and visual display of the patterns among the taxa inherent in these measures. Three different measures have been proposed in the literature, and three different summaries have been used. These different techniques are empirically compared using a data set consisting of gene sequences from seven species of Apicomplexa. The results suggest that the manhattan distance measure may be preferable to the use of the chi-square measure, although the separation of amino acid usage and codon usage by the genetic distance produces theoretical advantages. The multidimensional scaling ordination and unweighted pair-group clustering are both successful in displaying the patterns, while the eigenanalysis ordination is not.

Animals↗
PubMed1994

Percutaneous transluminal angioplasty of saphenous vein grafts for medically refractory unstable angina.

OBJECTIVES: We attempted to answer the question, Is balloon angioplasty a reasonable alternative to repeat coronary artery bypass graft surgery in patients with previous coronary bypass graft surgery, medically refractory unstable angina and vein graft lesions? BACKGROUND: Patients with medically refractory unstable angina need revascularization. Patients with previous coronary artery bypass graft surgery and medically refractory angina are at "high risk" for adverse outcomes with repeat coronary bypass graft surgery. Conversely, patients with angioplasty of old vein grafts are also at "high risk" for adverse outcomes. METHODS: Balloon angioplasty of 89 lesions in saphenous vein grafts was performed in 75 consecutive patients with medically refractory unstable angina. Of these 75 patients, 24 (32%) had myocardial infarct within 30 days, 23 (31%) had left ventricular ejection fraction < 0.35, and 50 (67%) had major comorbidity. Patients underwent standard balloon angioplasty with aggressive use of intravenous and intracoronary heparin, urokinase, nitroglycerin, oral aspirin, calcium channel blocking agents and coumadin. RESULTS: Angiographic success (reduction of stenosis < or = 50% without major complication) was seen in 84 of 89 lesions. Clinical success (angiographic success plus hospital discharge without major complication) was seen in 70 of 75 patients. During index hospitalization, two patients (3%) died, two (3%) had nonfatal infarcts, and one (1%) had emergency reoperation (coronary bypass graft surgery). In late follow up (3 to 66 months), 14 (20%) patients were lost to follow-up, 17 (23%) had repeat percutaneous transluminal coronary angioplasty, 2 (3%) had late bypass graft reoperation, 18 (25%) had late death, and 1 (< 1%) had a heart transplant. Of the 41 patients alive after one or more angioplasties, 25 have little or no angina, and 16 have occasional or more angina. We compared long-term survival rate in these 75 patients with a cohort of patients with high risk, unstable angina from the Veterans Affairs Surgical Registry (2,570 patients). The 30-day survival rate was better in patients with coronary angioplasty (97% vs. 92%, p < 0.05), but by 6 months there was no difference, and by 5 years a trend toward a higher survival rate with coronary artery bypass graft surgery was seen. CONCLUSIONS: Balloon angioplasty of saphenous vein grafts with aggressive adjunctive pharmacotherapy is a reasonable alternative to repeat coronary bypass graft surgery in patients with medically refractory unstable angina, previous coronary bypass graft surgery and saphenous vein narrowing.

Aged↗
PubMed1994

Codon usage and bias among individual genes of the coccidia and piroplasms.

Codon usage has been analysed in individual gene sequences, derived from a variety of parasitic protozoa in the class Sporozoa of the phylum Apicomplexa using metric multidimensional scaling. The two groups of codon usage patterns detected reflect the two main subgroups of organisms studied (the coccidia and the piroplasms), and it is the pattern of usage of synonymous codons that has the largest influence on overall codon usage in the individual genes, rather than being the pattern of amino acid composition of the gene product. The magnitude of the codon usage bias in the sequences was determined using three commonly used indices-NC, GC3S and B. In general, although relatively low levels of codon usage bias were detected in these gene sequences, codon usage bias does explain at least some of the codon usage patterns observed. Codon usage bias was observed to be dependent on the overall base composition of the genes analysed, which in turn was reflected in the types of codons that were either over- or under-represented in the nucleotide sequences. In keeping with observations on prokaryotic organisms, it is speculated that the codon usage patterns detected in these parasitic protozoa are the result of directional mutation pressure on the base composition of the genomic DNA.

Animals↗
PubMed1993

Identification of a purC gene from Streptococcus pneumoniae.

A gene encoding 5'-phosphoribosyl-5-aminoimidazole-4-N-succinocarboxamide synthetase was identified in Streptococcus pneumoniae as a 708-bp segment of the genome encoding a 27,001-Da protein with strong similarity to known PurC proteins. The S. pneumoniae purC gene, found immediately adjacent to the competence induction genes, comAB, was cloned and sequenced. The predicted protein product of purC displayed substantial (> 40%) identity to the entire sequence of the PurC proteins of Bacillus subtilis and Escherichia coli. Function of the S. pneumoniae gene product was demonstrated by complementation of E. coli purC mutations.

Amino Acid Sequence↗
PubMed1992

Salvage angioplasty: an alternative to high risk surgery for unstable angina?

This prospective, Human Subjects Committee and Ethics Committee approved investigation was performed to determine if coronary angioplasty (PTCA) might be a reasonable alternative revascularization method for unstable angina patients thought to be at high risk for operative (CABG) mortality. Between March 1990 and October 1991, thirty-four consecutive patients with medically refractory rest angina were deamed to have high risk of surgical mortality and underwent PTCA without surgical backup. Predicted operative mortality was calculated for each patient based upon the VA Surgical Risk Assessment model. Angioplasty of 52 vessels was attempted. Reduction in lumenal narrowing to < 50% and improved angiographic flow was obtained in 47 vessels. There were four complicating infarctions. One death occurred in the lab, and three patients with unsuccessful angioplasty died within 30 days of pump failure. Relief of angina occurred in 30/34. Thirty patients were discharged home. In follow-up from 1 to 12 months, there have been 2 late sudden deaths at 4 months and 9 months, 1 death from lung cancer; 4 patients have stable exertional angina; 2 are awaiting heart transplant but are pain free, and one patient who had PTCA during cardiogenic shock from acute myocardial infarction had elective coronary artery bypass surgery. There have been no late myocardial infarctions. The observed angioplasty 30-day mortality of 11.8% (95% confidence limit 1% to 22.6%) compares favorably with the predicted operative mortality of 23.8% for this group. This prospective but non-randomized series supports the concept that balloon angioplasty may be a reasonable alternative to surgical intervention in some patients with unstable angina and high risk for surgery. A prospective randomized trial is warranted.

Adult↗
PubMed1992

Epidermal growth factor receptor in breast cancer: storage conditions affecting measurement, and relationship to steroid receptors.

This study investigates the effect of freezing and storage of tissue and subcellular fractions on the measurement of epidermal growth factor receptors (EGF-r); compares competition binding and single saturating dose assays (SSD) for quantitating EGF-r levels; investigates several tissues as potential quality control; and examines the relationship between EGF-r and hormone receptor expression in human breast cancers. Mouse and calf uterine cell membranes were preferred sources of quality control tissue with similar levels of high affinity EGF-r to human breast cancer tissue (less than 150-200 fmol/mg membrane protein). Studies using pooled mouse uterine tissues indicated a loss of 40% in EGF-r activity following a single-20 degrees C freeze/thaw cycle, while a breast cancer tissue showed a 75% loss, independent of storage temperature (liquid nitrogen, -70 degrees C, -20 degrees C). A single freeze/thaw cycle of mouse uterine broken cell pellets (nuclei plus membrane fraction) again indicated a loss of EGF-r irrespective of storage temperature (43% loss at -70 degrees C, 52% loss at -20 degrees C). In most cases irrespective of the tissue type or tissue fraction being stored, the length of storage had little impact on the extent of the loss in activity. A second freeze/thaw cycle of intact tissue, or freezing of broken cell pellets from a previously-frozen tissue, led to a further major or total loss of the remaining EGF-r. Overall these results are commensurate with the published effects of freezing and storage on estrogen receptor measurement. In addition, our studies suggest that the most suitable procedure for assaying frozen breast cancer specimens for EGF-r levels in conjunction with steroid receptor quantitation is to prepare and assay both cytosol and membrane fractions for their respective receptor content without further storage. A concordance of 86% was found in 44 breast cancers assayed for EGF-4 by saturation analysis and SSD. Statistically significant inverse relationships were found between EGF-r and estrogen and progesterone receptor levels in the study of approximately 350 breast cancer patients. No association was found with tumor stage or diameter, axillary node involvement, or patient age.

Animals↗
PubMed1992

Increased exercise capacity in hypoxemic patients after long-term oxygen therapy.

Low-flow continuous oxygen can lead to significant improvement in exercise capacity in selected patients with stable hypoxemic pulmonary disease. Although the mechanisms of improvement are incompletely understood, two tenable hypotheses are (1) the relief of hypoxic pulmonary vasoconstriction and (2) improved peripheral oxygen delivery. This prospective study was performed to examine these two hypotheses. Stable patients with hypoxemic lung disease performed symptom-limited ergometry with hemodynamic monitoring before and after greater than one month of long-term home oxygen therapy. There were 22 patients who increased exercise capacity by greater than 100 KPM/min and greater than 4 min duration and 11 patients who did not increase their exercise capacity greater than 2 min or in KPM/min. Neither the responders nor the nonresponders had significant changes in pulmonary pressures or resistances or effective arterial volume elastances at exercise after long-term O2 therapy. The responders had significant increases in oxygen delivery during exercise (148 +/- 33 ml/min vs 184 +/- 51 ml/min, p = 0.004), cardiac output (7.7 +/- 1.6 L/min vs 8.7 +/- 2.1 L/min, p = 0.003), and arterial oxygen content (18.6 +/- 2.6 ml/dl vs 20.2 +/- 2.8 ml/dl, p = 0.02). The nonresponders had no significant changes in these parameters during exercise. Increased exercise capacity in response to long-term O2 therapy is associated with increased O2 delivery not relief of hypoxic vasoconstriction (in terms of pressure or resistance or arterial elastance). Increased O2 delivery can accrue from both increased cardiac output and increased arterial O2 content. Increase in arterial O2 content is unique to O2 relative to all vasodilator drugs.

Exercise↗