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Biomedical subjects

A McGregor

Publications and source records attributed to A McGregor.

At least 19 recordsLinked to original sources
PubMed2006

Accuracy of frozen section in the diagnosis of liver mass lesions.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative frozen sections diagnosis of liver lesions thought to be malignant tumours. METHODS: 285 frozen sections of liver from 173 patients were reviewed. The examinations were done between 1998 and 2004. RESULTS: Final histological diagnosis was divided into positive (32%) and negative (68%) for malignancy. In four cases (2%), diagnosis was deferred to paraffin section. There was one false positive and two false negative diagnoses. Sensitivity was 96.9% and specificity was 99.1%, and the overall accuracy to determine the lesions was 95%. The cases were further analysed to ascertain the nature of diagnostic difficulties, which comprised pathological misinterpretation, sampling error, and technical imperfections. Biliary hamartoma was the most common entity that was confused with malignant tumours in frozen sections. CONCLUSIONS: The data are in accordance with those of similar studies in other sites, and confirm that the frozen section is an accurate and reliable method for intraoperative diagnosis of suspected liver lesions.

Adolescent↗
PubMed2004

Hippocampal lesions modulate both associative and nonassociative priming.

In associative priming, rats are more likely to orient to a visual stimulus whose memory has not been recently activated (V1) than to one whose memory has been recently activated (V2). However, rats with excitotoxic hippocampal lesions are more likely to orient to the primed V2 than to the unprimed V1. This study investigated the influence of hippocampal lesions on nonassociative priming. Rats received presentations of 2 visual stimuli, V1 and V2, that had been presented more (V2, primed) or less (V1, unprimed) recently. Control rats oriented to V1 rather than to V2, whereas hippocampal rats oriented to V2 rather than to V1. These results parallel those observed in an associative priming procedure and thereby suggest that the role of the hippocampus in priming is general.

Animals↗
PubMed2004

Hippocampal lesions disrupt navigation based on the shape of the environment.

Geometric information provided by the walls of an environment has a strong influence over hippocampal unit activity. This suggests that the hippocampus forms part of a cognitive mapping system that encodes geometric relationships between environmental cues and the animal's location. Here, the authors show for the first time that excitotoxic lesions of the hippocampus disrupt the ability of rats to navigate to a goal using shape information provided by a solid-walled arena and an array of identical landmarks. These results are consistent with cognitive mapping theories of hippocampal function and extend previous research by showing that hippocampal cell loss impairs navigation with respect to shape information provided by both physical barriers and an array of landmarks.

Animals↗
PubMed2004

Sensitivity and specificity of serology in determining recent acute Campylobacter infection.

BACKGROUND: The measurement of serum antibodies to Campylobacter spp. has been used to investigate links between prior Campylobacter infections and the development of Guillain-Barre syndrome and its variants. Little is known of the serum antibody response to acute infections in the short- or long-term. AIMS: The aims of the present study were to investigate the normal serum response to an acute Campylobacter infection and the sensitivity and specificity of anti-Campylobacter antibodies in determining recent Campylobacter infection. METHODS: An enzyme-linked immunosorbent assay (ELISA) method was used to measure serum anti-Campylobacter immunoglobulin G (IgG), IgA and IgM antibodies. Controls consisted of 420 blood donors without recent gastroenteritis, 25 patients with other gastrointestinal infections, 24 patients with neurological conditions not affecting the peripheral nerves and 19 patients with autoimmune disorders. Three patient groups were assessed: 99 patients with acute Campylobacter infections, all of whom were tested 3 weeks post-infection; 69 of these patients tested 3-6 months later; and 74 additional patients tested >20 months post-infection. Western blot analysis was performed on controls and patients with high titre anti-Campylobacter antibodies to assess for cross-reactivity and specificity. RESULTS: Following acute infections, all antibody classes rose in the majority of but not in all patients, followed by decreasing titres that did not return to baseline levels. Sixteen per cent of enteritis cases did not demonstrate a rise in titres and 9% of cases had significant levels of antibodies >20 months post-infection. The ELISA used was shown to be highly specific for the detection of Campylobacter antibodies. CONCLUSION: The use of Campylobacter-specific antibody levels as the sole marker of prior infection is an unreliable method of determining the association between Campylobacter infection and neurological disease.

Acute Disease↗
PubMed2003

Fitness standards in airline staff.

Employers have a legal duty to manage safety and to meet this duty it is necessary to control risks arising from pre-existing medical conditions. Such conditions can be identified at the time of job placement, but there is little published information about the approach to fitness standards by most airlines. This review is therefore limited to the practice of one major airline. It is illustrated by reference to various occupations within the airline, with the associated rationale.

Aerospace Medicine↗
PubMed2002

Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices.

We show that matrices carrying the tethered homologs of natural phosphoinositides can be used to capture and display multiple phosphoinositide binding proteins in cell and tissue extracts. We present the mass spectrometric identification of over 20 proteins isolated by this method, mostly from leukocyte extracts: they include known and novel proteins with established phosphoinositide binding domains and also known proteins with surprising and unusual phosphoinositide binding properties. One of the novel PtdIns(3,4,5)P3 binding proteins, ARAP3, has an unusual domain structure, including five predicted PH domains. We show that it is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6 GAP both in vitro and in vivo, and both its Arf GAP and Rho GAP domains cooperate in mediating PI3K-dependent rearrangements in the cell cytoskeleton and cell shape.

ADP-Ribosylation Factor 6↗
PubMed2001

A larger hippocampus is associated with longer-lasting spatial memory.

Volumetric studies in a range of animals (London taxi-drivers, polygynous male voles, nest-parasitic female cowbirds, and a number of food-storing birds) have shown that the size of the hippocampus, a brain region essential to learning and memory, is correlated with tasks involving an extra demand for spatial learning and memory. In this paper, we report the quantitative advantage that food storers gain from such an enlargement. Coal tits (Parus ater) a food-storing species, performed better than great tits (Parus major), a nonstoring species, on a task that assessed memory persistence but not on a task that assessed memory resolution or on one that tested memory capacity. These results show that the advantage to the food-storing species associated with an enlarged hippocampus is one of memory persistence.

Animals↗
PubMed2001

Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence.

The two prohibitin proteins, Phb1p and Phb2p(BAP37), have been ascribed various functions, including cell cycle regulation, apoptosis, assembly of mitochondrial respiratory chain enzymes, and aging. We show that the mammalian prohibitins are present in the inner mitochondrial membrane and are always bound to each other, with no free protein detectable. They are coexpressed during development and in adult mammalian tissues, and expression levels are indicative of a role in mitochondrial metabolism, but are not compatible with roles in the regulation of cellular proliferation or apoptosis. High level expression of the proteins is consistently seen in primary human tumors, while cellular senescence of human and chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The two proteins are induced by metabolic stress caused by an imbalance in the synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do not respond to oxidative stress, heat shock, or other cellular stresses. The gene promoter sequences contain binding sites for the Myc oncoprotein and overexpression of Myc induces expression of the prohibitins. The data support conserved roles for the prohibitins in regulating mitochondrial respiratory activity and in aging.

Animals↗
PubMed2001

Inhibition of mitochondrial protein synthesis promotes autonomous regulation of mtDNA expression and generation of a new mitochondrial RNA species.

Mammalian mitochondria are known to proliferate in response to several stimuli. Proliferation requires an increase in expression of genes encoding proteins involved in mitochondrial biogenesis, as well as in the replication and expression of mitochondrial DNA (mtDNA). In contrast, we report that inhibiting mitochondrial protein synthesis causes a modulation in mtDNA gene expression without the concomitant increase in proliferative markers. Further, inhibition results in the production of a previously unidentified light-strand mitochondrial RNA that spans the entire displacement loop, the function of which is currently unknown.

Base Sequence↗
PubMed2001

Molecular cloning of the guinea pig cytomegalovirus (GPCMV) genome as an infectious bacterial artificial chromosome (BAC) in Escherichia coli.

Since cytomegalovirus (CMV) infection is highly species-specific, it is necessary to study animal cytomegaloviruses to assess viral factors which contribute to pathogenesis. The generation of recombinant viruses carrying reporter genes would provide useful tools for studying the genetics of CMV pathogenicity in vivo. We evaluated whether the guinea pig cytomegalovirus (GPCMV) was amenable to such manipulation. Metabolic selection using the guanosylphosphoribosityl transferase (gpt) gene facilitated recovery of a recombinant virus, vAM403, containing a gpt/green fluorescent protein (eGFP) cassette introduced into the HindIII "N" region of the viral genome. This virus had replication kinetics identical to wild-type virus. We next attempted to clone the GPCMV genome as a bacterial artificial chromosome (BAC). A BAC plasmid containing a gpt/eGFP cassette and the chloramphenicol resistance marker was introduced into HindIII "N" to generate another GPCMV recombinant, vAMBGPCMV. Circular viral DNA isolated from vAMBGPCMV-infected cells was used to transform Escherichia coli. Restriction profiles revealed that the GPCMV genome had been cloned as a BAC plasmid, and transfection of BAC plasmid DNA confirmed that the BAC clone was infectious. A novel strategy based on a unique PmeI site was devised to quickly modify the BAC GPCMV plasmid. Recombinants retained the capability to replicate and express reporter genes in guinea pigs, suggesting that these viruses will be useful for in vivo pathogenesis studies.

Animals↗
PubMed2001

Recent advances in herpesvirus genetics using bacterial artificial chromosomes.

Although the members of the Herpesvirus family are responsible for a wide variety of human diseases, advances in the understanding of viral molecular mechanisms of pathogenesis have been hampered by the large size of herpesvirus genomes, rendering the viruses difficult to experimentally manipulate. Better techniques have been needed to facilitate mutagenesis of herpesvirus genomes, allowing for the assessment of the role of specific viral gene products in replication, immunity, and pathogenesis. Homologous recombination with plasmids containing genes of interest flanked by selectable markers has been a successful method for generating viral mutants, as has the generation of recombinant virus from transfection of cosmid clones. Although these efforts to generate recombinant viruses have met with modest success, the protocols have been cumbersome. More recently, a novel technique for the manipulation of herpesvirus genomes has been developed. This technology utilizes bacterial F plasmids, and allows for the stable cloning of herpesvirus genomes as bacterial artificial chromosomes (BACs) in Escherichia coli. Once cloned, such BACs are stable, and DNA purified from E. coli is infectious, fully capable of reproducing replication-competent virus. Manipulation of herpesvirus genomes is now feasible using the powerful techniques of bacterial genetics, and should facilitate a better understanding of the molecular pathogenesis of herpesvirus infections.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Absence of expression from RNA internalised into electroporated mammalian mitochondria.

Transfection of mammalian mitochondria has proved to be notoriously difficult. Whilst there have been sporadic reports of import of foreign nucleic acids into isolated organelles, these imported nucleic acids have never been demonstrated to be functional. Inability to manipulate mitochondrial gene expression has hampered our understanding of RNA processing, maturation and translation in mitochondria. In an attempt to establish a model system for mt-RNA expression, we have electroporated rat liver mitochondria and mitoplasts in the presence of various RNA constructs built around the mitochondrial reporter gene mt-luciferase. Following electroporation, a fraction of the RNA was shown to be stably maintained, mitochondria remained coupled for oxidative phosphorylation and intramitochondrial protein synthesis was unaffected. In no case, however, was this RNA translated.

Animals↗
PubMed2001

Anterior cruciate ligament rupture: reconstruction surgery and rehabilitation. A nation-wide survey of current practice.

A database of the current practice of anterior cruciate ligament (ACL) reconstruction surgery in Great Britain was collated from a postal survey. This survey revealed that clear trends are emerging in the United Kingdom (UK) with regard to ACL reconstruction surgery (such as the type of graft used and timing of surgery) and rehabilitation. Certain issues, however, remain controversial, including bracing and knee range of movement. Clinical outcome measures are consistently used to judge operative success, but few specialists use defined objective measurements such as the IKDC scoring system.

Anterior Cruciate Ligament↗
PubMed2001

Fibre-optic bronchoscopy in adults: a position paper of The Thoracic Society of Australia and New Zealand.

Fibre-optic bronchoscopy in adults is a common procedure in clinical respiratory practice. Under controlled conditions it is safe, resulting in relatively few significant adverse events. The present position paper updates guidelines previously published by The Thoracic Society of Australia and New Zealand and is based on evidence obtained by searching the Medline and Embase databases. The level of evidence to support recommendations is indicated in the text. Where no evidence has been found, the guidelines reflect the opinions of the authors. Specific recommendations are made regarding sedation and anaesthesia, the cleaning of bronchoscopes and the training of bronchoscopists.

Adult↗
PubMed2001

A comparison of dermal and cadaveric pericardial grafts in the modified Horton-Devine procedure for Peyronie's disease.

PURPOSE: Penile curvature due to Peyronie's disease is often treated with plaque incision or excision and grafting. The advantages of various graft materials have long been debated. We studied the outcomes of dermal and cadaveric pericardial grafts after plaque incision or excision for Peyronie's disease. MATERIALS AND METHODS: We retrospectively evaluated all modified Horton-Devine procedures performed between February 1998 and April 2000. Dermal graft harvested from the lower abdomen or commercially available cadaveric pericardium was used to cover the corporeal defect. A followup telephone questionnaire was administered to determine patient satisfaction and function. RESULTS: We reviewed the records of 27 men, including 18 and 9 who received a dermal and pericardial graft, respectively. We successfully contacted 24 patients, including 15 with a dermal and 9 with a pericardial graft, to evaluate satisfaction. Average postoperative followup was 10 months. Of the 24 patients, 22 reported successful coitus and 15 (63%) needed assistance to achieve erection rigid enough for satisfactory coitus. Eight patients reported recurrent curvature, which was minimal and did not hamper sexual function. Overall 11 of the 15 patients with a dermal and 8 of the 9 with a pericardial graft would undergo the surgery again or recommend it to others. CONCLUSIONS: The results of the dermal and cadaveric pericardial grafts were comparable. The minimal preoperative preparation, decreased patient morbidity and pliability of cadaveric pericardium make it an attractive suitable graft substitute in the modified Horton-Devine procedure. Longer followup and larger patient series are needed to confirm the advantages of cadaveric pericardium.

Adult↗
PubMed2000

HIV-1 reverse transcriptase-pseudoknot RNA aptamer interaction has a binding affinity in the low picomolar range coupled with high specificity.

Systematic evolution of ligands by exponential enrichment (SELEX) is a powerful method for the identification of small oligonucleotides that bind with high affinity and specificity to target proteins. Such DNAs/RNAs are a new class of potential chemotherapeutics that could block the enzymatic activity of pathologically relevant proteins. We have conducted a detailed biochemical study of the interaction of human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) with a SELEX-derived pseudoknot RNA aptamer. Electron paramagnetic resonance spectroscopy of site-directed spin-labeled RT mutants revealed that this aptamer was selected for binding to the "closed" conformation of the enzyme. Kinetic analysis showed that the RNA inhibitor bound to HIV RT in a two-step process, with association rates similar to those described for model DNA/DNA and DNA/RNA substrates. However, the dissociation of the pseudoknot RNA from RT was dramatically slower than observed for model substrates. Equilibrium binding studies revealed an extraordinarily low K(d), of about 25 pm, for the enzyme-aptamer interaction, presumably a consequence of the slow off-rates. Additionally, this pseudoknot aptamer is highly specific for HIV-1 RT, with the closely related HIV-2 enzyme showing a binding affinity close to 4 orders of magnitude lower.

Crystallography, X-Ray↗