PubMed Health⌕ Search

Biomedical subjects

D A Morrison

Publications and source records attributed to D A Morrison.

At least 19 recordsLinked to original sources
PubMed2006

Population genetics of the bovine/cattle lungworm (Dictyocaulus viviparus) based on mtDNA and AFLP marker techniques.

Mitochondrial DNA (mtDNA) sequence data and amplified fragment length polymorphism (AFLP) patterns were compared for the lungworm Dictyocaulus viviparus, a nematode parasite of cattle. Eight individual D. viviparus samples from each of 8 herds in Sweden and 1 laboratory isolate were analysed, with the aim of describing the diversity and genetic structure in populations using different genetic markers on exactly the same DNA samples. There was qualitative agreement between the whole-genome AFLP data and the mtDNA sequence data, both indicating relatively strong genetic differentiation among the Swedish farms. However, the AFLP data detected much more genetic variation than did the mtDNA data, even after allowing for the different inheritance patterns of the markers, and indicated that there was much less differentiation among the populations. The mtDNA data therefore seemed to be more informative about the most recent history of the parasite populations, as the general patterns were less obscured by detailed inter-relationships among individual worms. The 4 mtDNA genes sequenced (1542 bp) showed consistent patterns, although there was more genetic variation in the protein-coding genes than in the structural RNA genes. Furthermore, there appeared to be at least 3 distinct genetic groups of D. viviparus infecting Swedish cattle, 1 of which was predominant and showed considerable differentiation between farms, but not necessarily within farms. Second, the 2 smaller genetic groups occurred on farms where the predominant group also occurred, suggesting that these farms have had multiple introductions of D. viviparus.

Animals↗
PubMed2006

Characterization of an atypical antigen from Sarcoptes scabiei containing an MADF domain.

We have cloned a cDNA encoding a novel antigen from a Sarcoptes scabiei (Acari) cDNA library by immunoscreening with sera from S. scabiei-infected dogs. The antigen is encoded by a 2,157 bp mRNA with a predicted open reading frame of 719 amino acids (molecular weight 79 kDa). Our sequence analysis identified the presence of a MADF domain in the N-terminus, and downstream of this domain there was a region of low sequence complexity. This latter region contained several blocks of triplets and quadruplets of polar amino acids (Asn, Gln and Ser), and these 3 amino acids represented 39.7% of all amino acids. The antigen was named Atypical Sarcoptes Antigen 1 (ASA1) since the MADF domain normally is found in proteins involved in transcriptional regulation. In addition, 15 out of 62 S. scabiei-infected dogs reacted with a purified recombinant version of ASA1 in Western blot analysis. With immunohistochemistry we could show that ASA1 is expressed throughout the parasite, and that IgG specific for ASA1 binds to the inside wall of the mite's burrow. To our knowledge, this is the first description of an antigen containing an MADF domain.

Amino Acid Sequence↗
PubMed2006

Biological control of sheep parasites using Duddingtonia flagrans: trials on commercial farms in Sweden.

Trials were conducted on 3 commercial sheep farms in Sweden to assess the effect of administering spores of the nematode trapping fungus, Duddingtonia flagrans, together with supplementary feed to lactating ewes for the first 6 weeks from turn-out on pastures in spring. Also control groups of ewes, receiving only feed supplement, were established on all 3 farms. Groups were monitored by intensive parasitological investigation. The ewes and their lambs were moved in late June to saved pastures for summer grazing, the lambs receiving an anthelmintic treatment at this time. After approximately 6 weeks on summer pasture the lambs were weaned, treated a second time with anthelmintic, and returned to their original lambing pastures for finishing. Decisions as to when lambs were to be marketed were entirely at the discretion of the farmer co-operators. No difference in lamb performance was found between the two treatments on all three farms. This was attributed to the high levels of nutrition initially of the ewes limiting their post-partum rise in nematode faecal egg counts in spring, which in turn resulted in low levels of nematode infection on pastures throughout the autumn period. Additionally, pastures were of good quality for the lambs during the finishing period, so they grew at optimal rates as far as the farmers were concerned.

Animal Husbandry↗
PubMed2005

Testing the hypothesis of recent population expansions in nematode parasites of human-associated hosts.

It has been predicted that parasites of human-associated organisms (eg humans, domestic pets, farm animals, agricultural and silvicultural plants) are more likely to show rapid recent population expansions than are parasites of other hosts. Here, we directly test the generality of this demographic prediction for species of parasitic nematodes that currently have mitochondrial sequence data available in the literature or the public-access genetic databases. Of the 23 host/parasite combinations analysed, there are seven human-associated parasite species with expanding populations and three without, and there are three non-human-associated parasite species with expanding populations and 10 without. This statistically significant pattern confirms the prediction. However, it is likely that the situation is more complicated than the simple hypothesis test suggests, and those species that do not fit the predicted general pattern provide interesting insights into other evolutionary processes that influence the historical population genetics of host-parasite relationships. These processes include the effects of postglacial migrations, evolutionary relationships and possibly life-history characteristics. Furthermore, the analysis highlights the limitations of this form of bioinformatic data-mining, in comparison to controlled experimental hypothesis tests.

Animals↗
PubMed2005

Multivessel percutaneous coronary intervention: a new paradigm for a new century.

Percutaneous coronary intervention (PCI) was introduced in 1977, to treat single, discrete lesions in patients with stable symptoms, and favorable anatomy. Increased operator experience and numerous technical advances, notably including bare-metal stents (BMS) and then drug-eluting stents (DES), and a number of adjunctive pharmacologic modalities, have allowed for the gradual application of PCI to far more diverse clinical and anatomic subsets. The proper role of PCI, compared with both medical therapy and coronary artery bypass graft (CABG) surgery, is evolving. This manuscript is synthesized from literature review of randomized clinical trials, and some cohort investigations, and 21 years of PCI experience, which has been focused on high-risk patients. Current American College of Cardiology/ American Heart Association/ Society for Cardiac Angiography and Interven-tions (ACC/AHA/ SCA&I) Guidelines, and most research, are based upon a perspective (conventional paradigm') that categorizes patients primarily based upon number of major' coronary (left anterior descending artery, circumflex and right) arteries with a >70% stenosis, and whether left ventricular function is normal or abnormal (left ventricular ejection fraction < or >0.50). This paradigm developed when: a) CABG was the only revascularization option, and b) medical therapy was quite limited. All of the trials demonstrating survival benefit with aspirin, clopidogrel, statins, angiotensin-converting-enzyme inhibition (ACE-I) or angiotensin receptor blockers (ARB), and beta-blockers; coupled with the PCI versus thrombolytics trials in ST-elevation myocardial infarction (STEMI), and non-STEMI strategy trials, both of which include revascularization almost exclusively by PCI, make this conventional paradigm, outdated and counterproductive. Attempts to compare CABG and PCI have de-emphasized their very different advantages and disadvantages. The new paradigm makes major division of patients based upon whether patients have stable or unstable: a) ischemia and b) hemodynamics, and c) whether they are having acute myocardial infarction (MI). The first issue to be settled is whether the patient is likely to benefit from revascularization. If little or no benefit can be envisioned, the patient should be managed medically. Unstable ischemia and unstable hemodynamics, and acute MI, all favor emergent or urgent revascularization. Clinical features, which generally favor PCI for revascularization, include hemodynamic instability, STEMI and non-STEMI; and severe comorbidity, particularly cerebral, pulmonary, or hepatic comorbidity. Anatomic features, which generally favor CABG, include unprotected left main stenosis, especially involving the bifurcation, one or more graftable chronic total occlusions (CTO), and bifurcation disease with large important side-branches. Old age and severely reduced left ventricular function are associated with higher risks, with either CABG or PCI. Small caliber and diffusely diseased vessels may imply lower expectation of success, by either CABG or PCI.

Angioplasty, Balloon, Coronary↗
PubMed2005

How old are the extant lineages of Toxoplasma gondii?

Most known isolates of Toxoplasma gondii belong to one of only three lineages, which are presumed to be clonal. Three models have been proposed for the evolutionary relationship of these lineages to the other extant lineages: Model (a) proposing that all lineages are derived from a most recent common ancestor (MRCA) in the distant past, Model (b) that all lineages are derived from a MRCA in the very recent past, and Model (c) that the clonal lineages share a recent MRCA but are related to the other lineages only in the distant past. Here, I test these models using DNA intron and coding-sequence data for loci at 14 genes, using three different methods to calculate the time of the MRCA. All of the calculations agree that the MRCA of the clonal lineages was > 70% of the age of the MRCA of all lineages, thus favouring Model (a). The MRCA may have existed approximately 150,000 years ago, with the clonal lineages expanding in prevalence approximately 10,000 years ago.

Animals↗
PubMed2004

Genetic diversity assessed by amplified fragment length polymorphism analysis of the parasitic nematode Dictyocaulus viviparus the lungworm of cattle.

We have examined the population genetic structure in a collection of nine isolates of the parasitic lungworm Dictyocaulus viviparus. Eight of the isolates were sampled from cattle in geographically separated farms throughout south-central Sweden, and one isolate was a laboratory strain that has been maintained in experimentally infected calves for almost four decades. A total of 72 worms were examined, with eight individual worms from the same individual host representing each isolate. The genetic variation as revealed by amplified fragment length polymorphism analysis using four selective primer combinations was high. Depending on the primer combination a total of 66-79 restriction fragments were amplified, with 26-44 peaks of similar complexity from each of the isolates. The heterozygosity within populations was relatively small, as were the population mutation and immigration rates, which seemed to be in neutral equilibrium. The genetic diversity was therefore reasonably well structured in the field; and the laboratory isolate was quite distinct from the field samples. There was no relationship between the patterns of genetic diversity and the geographical proximity of the farms. The estimates of heterozygosity were much larger and more consistent than those previously estimated for this nematode species using mitochondrial sequencing, and the genetic structuring was thus much less pronounced and the gene flow greater. We attribute these differences in estimation to the broader sampling of loci available using amplified fragment length polymorphism markers, which may therefore constitute a superior technique for the study of patterns of lungworm diversity. Furthermore, the data estimating gene flow for D. viviparus was less than previously reported for closely related species in North America. This might be related to different rates of movements of infected hosts. It seems likely that lungworm infections are rather persistent on different farms, and the sudden outbreaks of disease that can be observed with host movements are most likely to be related to the introduction of susceptible stock.

Animals↗
PubMed2003

Phylogeny of Dictyocaulus (lungworms) from eight species of ruminants based on analyses of ribosomal RNA data.

In this study, we conducted phylogenetic analyses of nematode parasites within the genus Dictyocaulus (superfamily Trichostrongyloidea). Lungworms from cattle (Bos taurus), domestic sheep (Ovis aries), European fallow deer (Dama dama), moose (Alces alces), musk ox (Ovibos moschatus), red deer (Cervus elaphus), reindeer (Rangifer tarandus) and roe deer (Capreolus capreolus) were obtained and their small subunit ribosomal RNA (SSU) and internal transcribed spacer 2 (ITS2) sequences analysed. In the hosts examined we identified D. capreolus, D. eckerti, D. filaria and D. viviparus. However, in fallow deer we detected a taxon with unique SSU and ITS2 sequences. The phylogenetic position of this taxon based on the SSU sequences shows that it is a separate evolutionary lineage from the other recognized species of Dictyocaulus. Furthermore, the analysis of the ITS2 sequence data indicates that it is as genetically distinct as are the named species of Dictyocaulus. Therefore, either this taxon needs to be recognized as a new species, or D. capreolus, D. eckerti and D. viviparus need to be combined into a single species. Traditionally, the genus Dictyocaulus has been placed as a separate family within the superfamily Trichostrongyloidea. The present molecular phylogenetic analyses support the placement as a separate family, but the current data do not support the placement of the Dictyocaulidae within the Trichostrongyloidea without a reassessment of the placement of the superfamily Strongyloidea. While D. eckerti has been regarded as the one and only lungworm species of cervids, this study showed that 4 host species including 3 members of Cervidae (moose, reindeer, red deer) and 1 Bovidae (musk ox) were infected with this parasite. Host ranges of D. viviparus (cattle), D. filaria (sheep) and D. capreolus (moose and roe deer) were more restricted. No clear pattern of co-evolution between the dictyocaulid taxa and their bovid and cervid hosts could be determined.

Animals↗
PubMed2003

Characterization of an alpha tubulin gene sequence from Neospora caninum and Hammondia heydorni, and their comparison to homologous genes from Apicomplexa.

The gene coding for a tubulin has been isolated by the polymerase chain reaction and sequenced from 2 isolates of Neospora caninum (Nc-Liverpool and Nc-SweB1). The data show that the gene, as in Toxoplasma gondii, is single copy and contains 3 exons and 2 introns and is identical in sequence in the 2 isolates studied. Comparison of the predicted protein sequence shows it to be identical to the a tubulin protein encoded by the T. gondii gene. The majority of the nucleotide substitutions that have occurred during the evolution of the T. gondii and N. caninum genes from their common ancestor have occurred in the third codon position. A partial coding sequence for a tubulin was also obtained from Hammondia heydorni and compared to other a tubulin sequences from Apicomplexa. The results show the sequences of the T. gondii, N. caninum and H. heydorni a tubulin genes to be similar but not identical in sequence, thereby providing new evidence that N. caninum and H. heydorni are genetically distinct species.

Amino Acid Sequence↗
PubMed2003

Balancing benefit against risk in the choice of therapy for coronary artery disease. Lesson from prospective, randomized, clinical trials of percutaneous coronary intervention and coronary artery bypass graft surgery.

The ageing world population faces a coming pandemic of high-risk coronary artery disease (CAD). Patients with CAD have 3 therapeutic options, which are based on objective clinical outcome: medical therapy and risk factor modification (Medicine), and 2 forms of revascularization, coronary artery bypass graft surgery (CABG), and percutaneous coronary intervention (PCI). More than 50 large (>100 patients), multicenter, prospective, randomized clinical trials (RCT) have compared these treatment options in terms of clinical benefits and patient risks. The randomized trials which demonstrated hard outcome (survival, myocardial infarction, stroke) benefits from statins, angiotensin-converting enzyme inhibition and thienopyridines have all been completed subsequent to the publication of most Medicine versus revascularization trials. These medical therapies, plus aspirin, beta-blockers, and risk factor modification, should be made available to patients regardless of the decision to revascularize, or the decision by what means (CABG or PCI). This review integrates the information from these trials, comparing the clinical benefits against the risks inherent in the 3 therapeutic options. The results of our review show that: trials of medicine versus revascularization (either CABG or PCI) support the revascularization paradox, in that the patients at highest risk of adverse outcome, from myocardial ischemia, have a hard outcome benefit (survival, MI, or stroke) from revascularization. This paradox, first seen in the Medicine versus CABG trials of the 1970s, is evident in the trials comparing fibrinolysis and other medicines, with primary PCI for ST-elevation myocardial infarction (MI). The paradox is evident in the conservative versus invasive strategy trials of non-ST-elevation MI and unstable angina, where the benefit of revascularization occurs only in high-risk subsets. The paradox often results in sicker patients, who have more to gain from revascularization, being denied it because of the elevated perception of risk (comparable to a reperfusion paradox in ST-elevation MI, where patients most likely to benefit from thrombolytics are denied them because of the perception of risk). Trials that compared medicine with revascularization for the treatment of acute MI support the use of PCI as the preferred early stabilization strategy (90% of all PAMI trial patients). The majority of the PCI versus CABG trials enrolled populations that were at relatively low risk for ischemic clinical events. These trials demonstrated few hard outcome (survival, MI, or stroke) differences between CABG and PCI. On the basis of the results obtained the following conclusions may be drawn: medicines are the primary options for stable, low-risk CAD, and should be given to all CAD patients. Medically refractory is a useful high-risk marker of potential benefit from revascularization. CABG continues to be the complete revascularization option for patients with multivessel, multi-lesion CAD, in part because of its application to chronic occlusions. PCI is the acute stabilization method of choice for patients with on-going ischemia and acute MI, especially among patients with hemodynamic compromise, and/or major comorbidity.

Angioplasty, Balloon, Coronary↗
PubMed2001

Complete genome sequence of a virulent isolate of Streptococcus pneumoniae.

The 2,160,837-base pair genome sequence of an isolate of Streptococcus pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low-guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.

Antigens, Bacterial↗
PubMed2001

Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME).

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS: Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS: Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Aged↗
PubMed2001

A functional genomic analysis of type 3 Streptococcus pneumoniae virulence.

Streptococcus pneumoniae remains a serious cause of morbidity and mortality in humans, but relatively little is known about the molecular basis of its pathogenesis. We used signature-tagged mutagenesis together with an analysis of S. pneumoniae genome sequence to identify and characterize genes required for pathogenesis. A library of signature-tagged mutants was created by insertion-duplication mutagenesis, and 1786 strains were analysed for their inability to survive and replicate in murine models of pneumonia and bacteraemia. One hundred and eighty-six mutant strains were identified as attenuated, and 56 were selected for further genetic characterization based on their ability to excise the integrated plasmid spontaneously. The genomic DNA inserts of the plasmids were cloned in Escherichia coli and sequenced. These sequences were subjected to database searches, including the S. pneumoniae genome sequence, which allowed us to examine the chromosomal regions flanking these genes. Most of the insertions were in probable operons, but no pathogenicity islands were found. Forty-two novel virulence loci were identified. Five strains mutated in genes involved in gene regulation, cation transport or stress tolerance were shown to be highly attenuated when tested individually in a murine respiratory tract infection model. Additional experiments also suggest that induction of competence for genetic transformation has a role in virulence.

Amino Acid Sequence↗
PubMed2001

An rpsL cassette, janus, for gene replacement through negative selection in Streptococcus pneumoniae.

Natural genetic transformation offers a direct route by which synthetic gene constructs can be placed into the single circular chromosome of Streptococcus pneumoniae. However, the lack of a general negative-selection marker has hampered the introduction of constructs that do not confer a selectable phenotype. A 1.3-kb cassette was constructed comprising a kanamycin (Kn) resistance marker (kan) and a counterselectable rpsL(+) marker. The cassette conferred dominant streptomycin (Sm) sensitivity in an Sm-resistant background in S. pneumoniae. It was demonstrated that it could be used in a two-step transformation procedure to place DNA of arbitrary sequence at a chosen target site. The first transformation into an Sm-resistant strain used the cassette to tag a target gene on the chromosome by homologous recombination while conferring Kn resistance but Sm sensitivity on the recombinant. Replacement of the cassette by an arbitrary segment of DNA during a second transformation restored Sm resistance (and Kn sensitivity), allowing construction of silent mutations and deletions or other gene replacements which lack a selectable phenotype. It was also shown that gene conversion occurred between the two rpsL alleles in a process that depended on recA and that was susceptible to correction by mismatch repair.

Anti-Bacterial Agents↗
PubMed2000

A phylogenetic study of the Anopheles punctulatus group of malaria vectors comparing rDNA sequence alignments derived from the mitochondrial and nuclear small ribosomal subunits.

A phylogenetic study of the members of the Anopheles punctulatus group was performed using structural and similarity-based DNA sequence alignments of the small ribosomal subunit (SSU) from both the nuclear and the mitochondrial genomes. The mitochondrial SSU gene (12S, approximately 650 bp) proved to be highly restricted by its secondary structure and displayed little informative sequence variation. Consequently, it was considered unsuitable for a phylogenetic study of these closely related mosquito species. A structural alignment of the nuclear ribosomal DNA SSU (18S, approximately 2000 bp) proved to be more informative than similarity-based alignments. Analyses showed the A. punctulatus group to be monophyletic with two major clades; a Farauti clade containing members displaying an all-black-scaled proboscis (A. farauti 1-3 and 5-7) and the Punctulatus clade containing members displaying extensive white scaling on the apical half of the proboscis (A. farauti 4, A. punctulatus, and An. sp. near punctulatus). Anopheles koliensis was positioned basal to the Farauti clade.

Animals↗