Biomedical subjects

D M Thomson

Publications and source records attributed to D M Thomson.

At least 19 recordsLinked to original sources

PubMed2006

Skeletal muscle and heart LKB1 deficiency causes decreased voluntary running and reduced muscle mitochondrial marker enzyme expression in mice.

LKB1 has been identified as a component of the major upstream kinase of AMP-activated protein kinase (AMPK) in skeletal muscle. To investigate the roles of LKB1 in skeletal muscle, we used muscle-specific LKB1 knockout (MLKB1KO) mice that exhibit low expression of LKB1 in heart and skeletal muscle, but not in other tissues. The importance of LKB1 in muscle physiology was demonstrated by the observation that electrical stimulation of the muscle in situ increased AMPK phosphorylation and activity in the wild-type (WT) but not in the muscle-specific LKB1KO mice. Likewise, phosphorylation of acetyl-CoA carboxylase (ACC) was markedly attenuated in the KO mice. The LKB1KO mice had difficulty running on the treadmill and exhibited marked reduction in distance run in voluntary running wheels over a 3-wk period (5.9 +/- 0.9 km/day for WT vs. 1.7 +/- 0.7 km/day for MLKB1KO mice). The MLKB1KO mice anesthetized at rest exhibited significantly decreased phospho-AMPK and phospho-ACC compared with WT mice. KO mice exhibited lower levels of mitochondrial protein expression in the red and white regions of the quadriceps. These observations, along with previous observations from other laboratories, clearly demonstrate that LKB1 is the major upstream kinase in skeletal muscle and that it is essential for maintaining mitochondrial marker proteins in skeletal muscle. These data provide evidence for a critical role of LKB1 in muscle physiology, one of which is maintaining basal levels of mitochondrial oxidative enzymes. Capacity for voluntary running is compromised with muscle and heart LKB1 deficiency.

AMP-Activated Protein Kinases↗

PubMed2000

Cost-effectiveness analysis of budesonide aqueous nasal spray and fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis.

BACKGROUND: An economic evaluation was performed analyzing direct medical costs in Canada for the treatment of perennial allergic rhinitis (PAR) with budesonide aqueous nasal spray and fluticasone propionate nasal spray. Three hundred fourteen patients with at least a 1-year history of PAR were randomized into a double-blind, parallel-group study of 6 weeks' duration. The treatments were daily doses of budesonide 256 microg, fluticasone propionate 200 microg, or placebo. Both active treatments produced significantly lower mean scores for overall nasal symptoms compared with placebo, and both were well tolerated. Budesonide was significantly more effective than fluticasone in reducing "blocked nose." METHOD: A retrospective cost-effectiveness analysis utilizing the clinical trial data was performed on the total costs of (1) budesonide-based and (2) fluticasone-based treatment strategies, including the relative importance of the drug costs in both strategies. RESULTS: The average treatment cost per patient in Canada over 12 months in the budesonide group was CAD 389.85 which was 23.3% lower than in the fluticasone group, which was CAD 508.06, due to lower drug acquisition costs (for the year 1998). CONCLUSION: Budesonide aqueous nasal spray was shown to be more cost-effective than fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis. This result is valid in the province of Ontario, Canada and in many other settings with the same structure of relative prices. The result is mainly driven by a difference in drug cost.

Androstadienes↗

PubMed1999

Should victim impact influence sentences? Understanding the community's justice reasoning.

Victim impact statements have been introduced in response to growing community concern about apparent neglect of victims in the criminal justice system. Their use in sentencing is a contentious issue, because victim characteristics such as resilience or fragility can contribute to impacts. Is it appropriate for sentences to be influenced by consequences arising from chance victim circumstances unforeseeable by the offender? In the interest of achieving an optimal fit between the justice system and community expectations, this research examined a neglected question: how does the public reason about the issue? Using offense vignettes presented to 260 people in Western Australia, sentencing decisions were found to vary according to consequences arising from victim characteristics. There was little to indicate participants fully appreciated the issue; thus, further research is needed to clarify how justice reasoning principles are used, and to ascertain whether different decisions are taken when people are informed about the problem.

Adolescent↗

PubMed1999

Aging and prospective memory: differences between naturalistic and laboratory tasks.

The contrasting age-related trends on laboratory and naturalistic prospective memory (PM) studies were investigated with the same participants. In the first two experiments, 380 participants in three age groups (20s, 60s, and 80+) were given a naturalistic PM task of logging the time at four set times for one week. There were six between-subjects regimens that varied the complexity of the time schedule, and the opportunity to use conjunction cues and external aids. The 60s and 80+ age groups did not differ and both older adult age groups were consistently superior to the young adults on all regimens. In Experiment 3, the same participants showed a significant age-related decline on retrospective memory tasks, and on event-based and time-based laboratory PM tasks embedded within the retrospective memory tasks. The study confirmed the paradoxical age-related trends on laboratory and naturalistic PM tasks.

Adolescent↗

PubMed1999

Macropodid herpesviruses 1 and 2 occupy unexpected molecular phylogenic positions within the Alphaherpesvirinae.

The molecular phylogeny of macropodid herpesviruses 1 and 2 (MaHV-1 and -2) has been investigated by cloning and sequencing the genes encoding glycoprotein B from both viruses. Phylogenetic reconstructions based on the putative amino acid sequences of glycoprotein B indicate that MaHV-1 and -2 are most closely related to the subfamily Alphaherpesvirinae. Within the Alphaherpesvirinae, MaHV-1 and -2 are closely associated with those herpesviruses that infect primates. This phylogenetic relationship does not fit the constraints of the proposed co-evolution theory described for other members of the Alphaherpesvirinae which have mammalian hosts.

Alphaherpesvirinae↗

PubMed1997

Localized unilateral periorbital edema induced by aspirin.

BACKGROUND: Aspirin intolerance manifested as bronchospasm or urticaria/angioedema has been observed since the beginning of this century. OBJECTIVE: To report a novel case of intolerance to aspirin ingestion. METHODS: Case report; routine skin testing; pulmonary function testing; aspirin challenge. RESULTS: A 30-year-old man with a history of left ocular trauma at the age of 10 noted a 3-year history of left periorbital angioedema after aspirin but not other nonsteroidal anti-inflammatory drugs. Incremental oral aspirin challenge resulted in this unilateral symptomatology at a dose of 673 mg. CONCLUSION: To the best of our knowledge, this is the first reported case of unilateral periorbital edema following aspirin ingestion.

Adult↗

PubMed1996

Children's memory of an occurrence of a repeated event: effects of age, repetition, and retention interval across three question types.

Children's memory of the final occurrence of a repeated event was examined whereby each occurrence had the same underlying structure but included unpredictable variations in the specific instantiations of items across the series. The event was administered by the children's teachers at the kindergarten or school. The effects of repetition (single vs. repeated event), age (4-5 vs. 6-8-year-olds), retention interval (1 week vs. 6 weeks), and the frequency of specific instantiations of items were examined across 3 question types. Repetition increased the number of items recalled on a level that was common to all occurrences in response to general probes and reduced the likelihood that children would report details that did not occur in the event. However, repetition also reduced the number of correct responses about which instantiation was included in the occurrence and decreased the consistency of responses across repeated questioning. Most errors were intrusions of details from other occurrences; usually references to instantiations of items that had occurred frequently throughout the series. The younger children showed a poorer ability to discriminate between the occurrences than the older children, but age differences were less evident at the longer retention interval. The results are discussed in relation to current theories of memory and children's eyewitness testimony.

Association Learning↗

PubMed1995

Development of face recognition.

In this article, research findings from studies which have examined the developmental pattern for recognition of unfamiliar faces and relevant theories are reviewed. Recognition of faces was found to improve with age from about five years to adulthood, with some studies reporting a dip during early adolescence. Two neuropsychological explanations (development of hemisphere specialization and maturational changes) and four information processing explanations (depth of face processing, pattern of feature salience, development of face schema, and encoding shift) are described and assessed for their tenability in light of reported findings. Explanations for the developmental dip are also discussed. Since these explanations failed to receive sufficient empirical support, an alternative explanation in terms of increasing efficiency of encoding is proposed.

Adolescent↗

PubMed1994

The diagnostic value of CA 27-29, CA 15-3, mucin-like carcinoma antigen, carcinoembryonic antigen and CA 19-9 in breast and gastrointestinal malignancies.

In the past decade, considerable interest has arisen for defining the role of various tumor markers in the diagnosis of cancer. This cross-sectional study evaluates four breast cancer markers (CA 27-29, CA 15-3, MCA and CEA) and two gastrointestinal (GI) markers (CA 19-9 and CEA) in 213 patients. Receiver operating curves (ROC) revealed a sensitivity for the 90% specificity cutoff for breast cancers compared to breast benign diseases of 70% for CA 27-29, 67.5% for CA 15-3, 52.5% for MCA and 40% for CEA. When GI tumors were compared to benign GI disease, the sensitivity for 90% specificity was 40.3% for CEA and 32.3% for CA 19-9. Comparison of breast cancer and GI malignancies with other malignancies leads to a marked shift of the ROC curve to the right and loss of specificity. Late stage for all breast and GI tumor markers was found to be a predictor of high serum antigen level (p < 0.001). The presence of liver metastases in breast cancer was associated with abnormal levels of CA 27-29 (p = 0.028). Pancreas adenocarcinomas had a higher CA 19-9 antigen level (p < 0.001) than other GI malignancies. CA 27-29 appears to be at least as sensitive and specific as CA 15-3 in patients with breast cancer. None of the above markers retain their specificity when compared with a control group consisting of other malignancies.

Adult↗

PubMed1993

Identification of a human cancer related organ-specific neoantigen.

Human cancers express organ-specific neoantigens (OSNs) which elicit specific cellular immune responses in the cancer patient, as demonstrated by leukocyte adherence inhibition (LAI), an in vitro immune response assay. A purified protein of MW 40,000 (p40) exhibiting OSN (colon specific) activity was cleaved into specific peptide fragments and their partial amino acid sequences determined. This information was used in the polymerase chain reaction (PCR) to obtain a 992 bp cDNA clone (PCR-992) from a human colon adenocarcinoma cell line (LS-180). By comparison of the predicted amino acid sequence of PCR-992 with the known sequence of p40 peptides, PCR-992 was shown to correspond to almost the entire coding region of p40. Nucleotide sequence analysis suggested that the protein was mycoplasmal in origin due to its high A+T content (76%) and the presence of five in frame TGA termination codons; at least two of the latter are actually read as tryptophan, a known feature of mycoplasma translation. We have confirmed this origin by direct isolation of a contaminating mycoplasma species from the LS-180 cell line and demonstration that it could be hybridized with the PCR-992 probe. Northern and PCR analysis of RNA preparations from the contaminated LS-180 cell line showed that p40 was part of the high affinity transport system operon of Mycoplasma hyorhinis (Dudler et al, EMBO J., 7: 3963-3970, 1988). Total protein lysates of Mycoplasma hyorhinis cultivated without animal cells could elicit positive LAI responses when incubated with cancer patient leukocytes but not with normal patient leukocytes. The organ-specific nature of the response was, however, not observed indicating that host cell-mycoplasmal interactions may play a role in determining the organ-specific nature of p40 seen with the LAI. The significance of these findings will be discussed in the context of previous thinking regarding the origin of OSNs.

Amino Acid Sequence↗

PubMed1992

Routine use of hair root or buccal swab specimens for PCR analysis: advantages over using blood.

We report the use of hair roots and buccal cells as specimens of choice for DNA analysis of genetic diseases in a service laboratory. Our protocols using these specimen types show superiority to those using blood specimens in the areas of collection, transport, storage and overall cost. Our experience using these specimen types for 319 cystic fibrosis delta F508 mutation tests and 62 Leber's hereditary optic neuroretinopathy mutation tests leads us to recommend that hair roots and buccal cells should be evaluated as specimens of first choice when developing PCR DNA analysis.

Base Sequence↗

PubMed1988

Comparison by leukocyte adherence inhibition of human immune response to cancer-associated immunogens, Thomsen-Friedenreich (T) and Tn, myelin basic protein, and organ-specific cancer neoantigens.

Peripheral blood leukocytes from cancer patients exhibit nonadherence to glass as an index of antigen recognition when incubated individually with four distinct, soluble tumor-related substances. Crude cancer extracts, purified antigens, T and Tn, myelin basic protein (MBP), and organ-specific cancer neoantigens (OSN), all elicited narrow dose-dependent leukocyte adherence inhibition (LAI) response curves. The present study focused on the reasons for the narrow antigen dose-LAI response relationship. Between 9 and 20 pmol of antigens elicited the maximum number of nonadherent leukocytes; cleavage products of T antigen and the nonapeptide (T18) of MBP required about a 10-fold increase in molar concentration for the same LAI response. When crude cancer extracts were combined with pure antigen or the pure antigens were combined at concentrations shown to give maximum LAI responses, the positive LAI responses were negated. The chemoattractant LTB4 at 10(-11) M triggered maximum LAI. But when MBP was added with the LTB4 at progressively increasing concentrations, there was dose-dependent negation of LAI. The magnitude of LAI depended on the total amount of mediator released rather than the rate of release. When leukocytes from cancer patients were incubated with optimum to high concentrations of MBP, the supernatants contained a mediator that gave similar bell-shaped dose-LAI responses on control leukocytes indicating that leukocytes from cancer patients react to a much broader range of antigen concentration than indicated by the LAI assay alone. High antigen dose negated LAI because of excess mediator production. Antigen-generated mediators had a biphasic effect inducing nonadherence and then adherence of leukocytes.

Antigens, Neoplasm↗

PubMed1988

An application of the repertory grid method to investigate consumer perceptions of foods.

This paper describes the development of a method for investigating consumer perceptions of foods. Each of 46 subjects independently used a version of Kelly's repertory grid method to elucidate the attributes (constructs) perceived in 25 meat products. Subjects then scaled the individual products with respect to each of their own constructs. Data were input to generalized Procrustes analysis to obtain a perceptual map of the products for each subject and a consensus product map. The principal components of the consensus map, and hence the important perceptual attributes, were interpreted by identifying the constructs which were most heavily weighted by individual subjects.

Adolescent↗

PubMed1988

Measurement by leukocyte adherence inhibition of autosensitization of cancer patients to myelin basic protein.

In vitro cell-mediated immunity was assayed by leukocyte adherence inhibition (LAI) to determine the extent of autosensitization to myelin basic protein (MBP). Leukocytes from 123 cancer patients, 16 patients freed of cancer, 135 patients with benign disease, and 26 patients with destruction of nervous parenchyma were tested. Most patients with cancer reacted to MBP: 92%, 93%, 82%, 78%, 75% and 62% for pancreatic, colonic, esophageal, lung, ovarian and breast. Few patients with benign diseases reacted to MBP. Patients with multiple sclerosis (MS) were sensitized to MBP, but patients with other nervous tissue injury did not react to MBP. Cancer patients did not remain sensitized to MBP once they were freed of their cancer. The LAI assay is a straightforward method of measuring cellular autosensitivity to MBP. In the population of patients tested, autosensitivity to MBP was confined, except for MS, principally to cancer patients.

Autoantigens↗

PubMed1988

Circulating form of beta-2-microglobulin in dialysis patients.

The circulating profile of beta-2-microglobulin (beta 2M) was determined in 8 end-stage renal disease patients on long-term dialysis (6 on hemodialysis, 2 on CAPD) by measuring beta 2M in different fraction after molecular sieve separation of their sera. Four patients had carpal tunnel syndrome with demonstrated amyloid in excised wrist tissues of which 2 were positive for beta 2M. In all patients despite very high blood levels (34.3-63.1 mg/l), beta 2M eluted exclusively as a single peak in the molecular weight region of about 12,000 daltons on a calibrated Sephacryl S-200 column. Recoveries from within the peak accounted for 96% of the applied beta 2M serum concentrations. These results were confirmed by molecular sieve separation of the enriched beta 2M-containing fractions by high-pressure liquid chromatography. We conclude that immunoreactive beta 2M in dialysis patients circulates as an intact monomer without evidence for the formation of aggregates or fragments. The pathogenesis of tissue deposition of this low-molecular-weight protein and its polymerisation to form a specific amyloid remains to be defined.

Adult↗

PubMed1987

Extraction of human organ-specific cancer neoantigens from cancer cells and plasma membranes with 1-butanol.

Immunoprotective tumor antigens of experimental tumors are selectively extracted by 1-butanol. Human organ-specific cancer neoantigens (OSNs) are tumor substances in cancer extracts to which patients with cancer of the same organ respond in the in vitro assay of leukocyte adherence inhibition. Here we determined whether OSNs as measured by leukocyte adherence inhibition assay are also selectively solubilized by 2.5% (v/v) 1-butanol. Butanol extracts of live tissue-cultured human cancer cells as well as extracts of primary breast cancer contained OSNs as determined by leukocyte reactivity in leukocyte adherence inhibition. With two-phase butanol, OSN activity was recovered in the aqueous and not in the organic phase, indicating that OSN is not a lipoprotein. The butanol-soluble OSN, whether allogeneic or autologous, was recognized by the T4 subset of T-cells in association with Class II major histocompatibility complex antigens of monocytes. Autologous OSN was extracted from membrane preparations of autologous primary cancer. Butanol extracts contained the previously identified Mr 40,000 protein OSN. Butanol removed about 50% of the Mr 40,000 protein OSN from live cancer cell membranes. Probably because of residual OSN in the membrane fragments and the ability of OSN to reassociate with the membrane, the T8 subset of pure T-cells responded positively to autologous cancer extracts. Passage of the autologous extract through an anti-Class I major histocompatibility complex antigen affinity column but not through a control affinity column negated the activity of the extract with pure autologous T-cells. The results indicate that human OSNs share with immunoprotective tumor antigens of experimental tumors the unique physicochemical property of being selectively extracted by 2.5% butanol.

1-Butanol↗

PubMed1987

Recognition of a purified Mr-40,000 organ-specific immunogen of human lung cancer by class II-restricted T-cells.

An Mr-40,000 polypeptide (p40) was purified from a lung cancer cell line on the basis of its antigenicity with leukocytes from lung cancer patients in an in vitro immunological assay of leukocyte adherence inhibition. Here, the cells and mechanism responsible for recognizing the purified p40 organ-specific cancer neoantigen (OSN) were studied. Buffy coat leukocytes from lung cancer patients showed a bell-shaped dose response with a peak response at 0.75 micrograms/assay. Mononuclear cells showed a similar response pattern, whereas pure T-cells were unreactive. Monoclonal antibodies (MAbs) to T-cell differentiation antigens T3 and T4 inhibited the response in a dose-dependent fashion, whereas anti-T8 had no effect, indicating T helper cells and their T3-antigen receptor complex recognized the antigen. MAbs to class II major histocompatibility complex (MHC) antigens also inhibited the response, whereas MAbs to class I MHC had no effect, indicating an important role for class II MHC antigens of monocytes. None of the MAbs inhibited the response to OSN on membrane fragments, which is mediated by antibody-dependent monocytes. Trypsin- or cyanogen bromide-cleaved p40 OSN triggered a response at the same concentrations as the intact molecule. The p40 OSN incubated with live leukocytes showed less than 30% proteolytic digestion. The results indicate that class II-restricted T-cells recognize, via their antigen-specific cell surface receptors, contiguous sequences within the immunogenic tumor molecule in the context of the molecule or peptides binding to class II transplantation antigens.

Antibodies, Monoclonal↗

PubMed1987

The objective structured clinical examination for general practice: design, validity and reliability.

This paper describes and analyses an experimental clinical examination for general practice. Differences in the results obtained by fourth year students, fifth year students and trainee general practitioners highlight some of the dilemmas of medical education. It is concluded that examinations which include clinical tests can increase the credibility of general practice examinations, can be reliably applied to small groups of candidates and therefore have considerable potential for formative assessment. The constraints of assuring inter-examiner reliability in a multicentre design, together with its labour intensive nature, would however make this type of examination difficult to adapt to the needs of national end-of-training examinations.

Clinical Competence↗