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M Johnston

Publications and source records attributed to M Johnston.

At least 73 records · Page 4Linked to original sources
PubMed2000

Alterations in the gene expression profile of MCF-7 breast tumor cells in response to c-Jun.

MCF7 breast tumor cells overexpressing human c-Jun exhibit a transformed phenotype characterized not only by increased tumorigenicity but also by enhanced motility and invasion. The cellular phenotypic response to c-Jun overexpression is likely due, at least in part, to altered patterns of gene expression. In order to begin to understand the complexities by which elevated production of c-Jun alters the state of the cell, we have profiled the expression of 588 different genes by comparative hybridization. By using this approach, we have identified a total of 21 upregulated or downregulated gene targets responsive to c-Jun overexpression. Interestingly, 8 of these genes have been previously found associated with c-Jun or AP-1 activity and therefore provide internal validation for this approach to target gene discovery. The remaining 13 genes represent potential new c-Jun regulated target genes. Genomic sequence information was available for 15 of the 21 genes identified in this screen. Analysis of these genomic sequences revealed the presence of AP-1 or AP-1-like sequences in 12 of the 15 genes examined. Consistent with a direct mechanism of target regulation by c-Jun, gel shift analysis of selected AP-1-containing promoter regions revealed elevated and specific binding by proteins present in nuclear extracts of c-Jun expressing MCF7 cells.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2000

The effects of hormone replacement therapy on thrombin generation, fibrinolysis inhibition, and resistance to activated protein C: prospective cohort study and review of literature.

Recent studies have found that hormone replacement therapy (HRT) is associated with a two- to fourfold increased risk of venous thromboembolism, but the thrombogenic mechanism of HRT remains unclear. To investigate whether HRT use induces a procoagulant state, we undertook a prospective cohort study in postmenopausal women to investigate the effects of 3 months of treatment with oral HRT (conjugated equine estrogen 0.625 mg daily and medroxyprogesterone 2.5 mg daily) on markers of thrombin generation (prothrombin fragment 1+2, thrombin-antithrombin complexes), fibrinolytic potential (plasminogen activator inhibitor-1 (PAI-1) activity), and activated protein C (APC) resistance. In addition, we reviewed the literature for studies investigating the effects of HRT on markers of thrombin generation and fibrinolytic potential. In 12 patients who received HRT for a mean of 3.8 months, there was no significant effect of HRT on levels of F1+2, thrombin-antithrombin complexes, or the APC ratio. HRT use had the greatest effect on PAI-1 activity (mean difference = -3.75 UI/mL; 95% confidence interval: - 8.9, 1.1) compared to other coagulation parameters, but this did not attain statistical significance (p = 0.12). In the literature review, the effects of HRT on markers of thrombin generation were inconsistent across studies. There was a consistent pattern of increased fibrinolytic potential with HRT use associated with one marker (PAI-1), but not with another marker (tissue plasminogen activator antigen). We conclude that there is a lack of consistent evidence that the increased risk of venous thromboembolism associated with HRT use is due to a procoagulant state related to increased thrombin generation, decreased fibrinolytic potential, or acquired APC resistance.

Activated Protein C Resistance↗
PubMed2000

Pharmacokinetic profile of a low-molecular weight heparin (reviparin) in pregnant patients. A prospective cohort study.

Anticoagulant therapy during pregnancy is problematic. Patients are frequently treated with long-term low-molecular weight heparin despite a lack of evidence for its effectiveness, and in the absence of validated dosing recommendations. The objectives of this investigation were to characterize the safety and pharmacokinetic behavior of a low-molecular weight heparin (reviparin) administered throughout pregnancy. Forty-two patients followed in a tertiary-care rheumatology clinic who received prophylactic doses of reviparin (4900 anti-Xa units subcutaneously once daily) were enrolled in this investigation. Anti-Xa heparin levels, weights, and gestational ages of the patients were obtained on up to four occasions distributed throughout their pregnancy. The achieved anti-Xa heparin levels were highly correlated with the patient's weight, irrespective of the gestational age. No toxicity other than injection site hematomas was observed. The achieved intensity of anticoagulation with reviparin varies during pregnancy in direct proportion to the patient's weight. This variability may mandate dose adjustment in response to changes in a patient's weight during pregnancy, particularly if low-molecular weight heparin is administered at therapeutic doses.

Abortion, Habitual↗
PubMed2000

Dilational processes accompanying earthquakes in the long valley caldera

Regional distance seismic moment tensor determinations and broadband waveforms of moment magnitude 4.6 to 4.9 earthquakes from a November 1997 Long Valley Caldera swarm, during an inflation episode, display evidence of anomalous seismic radiation characterized by non-double couple (NDC) moment tensors with significant volumetric components. Observed coseismic dilation suggests that hydrothermal or magmatic processes are directly triggering some of the seismicity in the region. Similarity in the NDC solutions implies a common source process, and the anomalous events may have been triggered by net fault-normal stress reduction due to high-pressure fluid injection or pressurization of fluid-saturated faults due to magmatic heating.

Journal Article↗
PubMed2000

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.

Two large-scale yeast two-hybrid screens were undertaken to identify protein-protein interactions between full-length open reading frames predicted from the Saccharomyces cerevisiae genome sequence. In one approach, we constructed a protein array of about 6,000 yeast transformants, with each transformant expressing one of the open reading frames as a fusion to an activation domain. This array was screened by a simple and automated procedure for 192 yeast proteins, with positive responses identified by their positions in the array. In a second approach, we pooled cells expressing one of about 6,000 activation domain fusions to generate a library. We used a high-throughput screening procedure to screen nearly all of the 6,000 predicted yeast proteins, expressed as Gal4 DNA-binding domain fusion proteins, against the library, and characterized positives by sequence analysis. These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. These data reveal interactions that place functionally unclassified proteins in a biological context, interactions between proteins involved in the same biological function, and interactions that link biological functions together into larger cellular processes. The results of these screens are shown here.

Fungal Proteins↗
PubMed2000

A child with ALL and ETV6/AML1 fusion on a chromosome 12 due to an insertion of AML1 and loss of ETV6 from the homolog involved in a t(12;15)(p13;q15).

A 4-year-old boy was found to have acute lymphoblastic leukemia characterized by a t(12;15)(p13;q15). FISH investigation using a TEL(ETV6)/AML1 probe detected a fusion signal in 98% of the interphase cells. Sequential FISH on a G-banded slide showed a fusion signal on an apparently normal chromosome 12 and AML1 signals on chromosomes 21. The ETV6 was deleted from the chromosome 12 involved in the t(12;15). These results are best explained as an insertion of AML1 into TEL on one chromosome arm 12p and loss of ETV6 from the chromosome 12 involved in the t(12;15).

Child, Preschool↗
PubMed2000

Relationship between pericardial pressure and lymphatic pericardial fluid transport in sheep.

We investigated the relationship between pericardial pressure and the volumetric lymphatic clearance rate of pericardial fluid in sheep. A single catheter perfusion system was established to deliver tracer to the pericardial cavity and control pericardial pressure. In addition, catheters were placed into the thoracic duct and into the jugular vein at the base of the neck. (125)I-human serum albumin (HSA) was administered into the pericardial perfusate to serve as the lymph flow marker and its concentration monitored in the effluent from the outflow end of the perfusion system. (131)I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, estimates of total pericardial clearance into lymphatics increased significantly as pericardial pressures were elevated in 2. 5 cm H(2)O increments from 2.5 to 12.5 cm H(2)O (P = 0.018). Pericardial lymph transport ranged from 0.89 +/- 0.10 to 3.09 +/- 0. 66 ml/h at 2.5 and 12.5 cm H(2)O pericardial pressure, respectively. The majority of transport occurred through mediastinal vessels with a small proportion (10.3 to 23.9%) being cleared into lymphatics leading to the thoracic duct. We conclude that lymphatic pericardial fluid transport increases approximately 3.5-fold over a pericardial pressure range that encompasses the transition between the shallow and steep portions of the pericardial pressure-volume relationship.

Animals↗
PubMed2000

Construct validation of the hospital anxiety and depression scale with clinical populations.

OBJECTIVE: the hospital anxiety and depression scale (HADS) attempts to measure anxiety and depression without confounding by somatic symptoms of physical disorder, and is widely used for this purpose. This paper addresses three questions about the validity of the HADS concerning its independence of physical symptoms, the extent to which its items robustly measure the identified constructs with varying clinical populations and situations, and its capacity to differentiate anxiety and depression. METHODS: data from patients with breast disease, myocardial infarction (MI), and stroke were examined using factor analytic and psychometric analyses. RESULTS: using exploratory factor analysis in patients with breast disease, 13 of the 14 HADS items fell on a psychological factor and loadings on the psychological factor were higher than loadings on the somatic factor for all items. The HADS showed high levels of internal consistency and there was little evidence that removing items would improve it. Confirmatory factor analyses (CFA) in MI and stroke groups confirmed the separation of anxiety and depression. Analyses indicated items, which were performing poorly for these clinical groups. CONCLUSIONS: there was support for the validity of the HADS for all three questions. However, there were some evidences of individual items performing poorly. Given the ease of administration and the acceptability of this measure to ill or weak respondents, the HADS continues to perform satisfactorily.

Adolescent↗
PubMed2000

The yeast genome: on the road to the Golden Age.

Having the complete genome sequence of Saccharomyces cerevisiae makes us aware of the ultimate goal of yeast molecular biology: the 'solution' of the cell, that is, an understanding of the function of all approximately 6000 proteins (and a few RNAs) and how they interact with each other and the environment. The recent development of 'genomic' approaches for studying gene function makes this goal seem reachable in the foreseeable future. When this is accomplished, we will have entered a Golden Age, when we will have the information necessary for designing truly incisive experiments to reveal biological function.

DNA, Fungal↗
PubMed2000

Grass-roots genomics.

In these heady days of genomic enterprise, the wet-bench geneticist may wonder what the future holds in store for those who explore biology in the laboratory. We argue that the goal of genomics is to serve geneticists.

Animals↗
PubMed2000

Increasing galactose consumption by Saccharomyces cerevisiae through metabolic engineering of the GAL gene regulatory network.

Increasing the flux through central carbon metabolism is difficult because of rigidity in regulatory structures, at both the genetic and the enzymatic levels. Here we describe metabolic engineering of a regulatory network to obtain a balanced increase in the activity of all the enzymes in the pathway, and ultimately, increasing metabolic flux through the pathway of interest. By manipulating the GAL gene regulatory network of Saccharomyces cerevisiae, which is a tightly regulated system, we produced prototroph mutant strains, which increased the flux through the galactose utilization pathway by eliminating three known negative regulators of the GAL system: Gal6, Gal80, and Mig1. This led to a 41% increase in flux through the galactose utilization pathway compared with the wild-type strain. This is of significant interest within the field of biotechnology since galactose is present in many industrial media. The improved galactose consumption of the gal mutants did not favor biomass formation, but rather caused excessive respiro-fermentative metabolism, with the ethanol production rate increasing linearly with glycolytic flux.

Bacterial Proteins↗
PubMed2000

Interventions to prevent weight gain: a systematic review of psychological models and behaviour change methods.

OBJECTIVE: To identify and review published interventions aimed at the prevention of weight gain. DESIGN: A systematic review of published interventions aimed at the prevention of weight gain. METHODS: Search strategies-we searched eight databases, manually checked reference lists and contacted authors. Inclusion and exclusion criteria-studies of any design, in which participants were selected regardless of weight or age, were included. Interventions targeting a specific subgroup, multifactorial interventions, interventions aimed at weight loss, and those with an ambiguous aim were excluded. Data extraction-data were extracted on behaviours targeted for change, psychological model, behaviour change methods and modes of delivery, methodological quality, characteristics of participants, and outcomes related to body weight and self-reported diet and physical activity. Classification and validation-a taxonomy of behaviour change programmes was developed and used for classification of underlying model, behaviour change methods, and modes of delivery. The data extraction and subsequent classification were independently validated. RESULTS: Eleven publications were included, describing five distinct interventions in schools and four in the wider community. Where diet and physical activity were described, positive effects were usually obtained, but all were measured by self-report. Effects on weight were mixed but follow-up was generally short. Smaller effects on weight gain were found among low-income participants, students and smokers. Many participants in the community-based studies were overweight or obese. Study dropout was higher among thinner and lower-income subjects. CONCLUSION: Interventions to prevent weight gain exhibited various degrees of effectiveness. Definite statements about the elements of the interventions that were associated with increased effect size cannot be made as only one of the five studies that involved an RCT design reported a significant effect on weight. This intervention involved a correspondence programme and a mix of behaviour change methods including goal setting, self-monitoring and contingencies. Future interventions might be more effective if they were explicitly based on methods of behaviour change that have been shown to work in other contexts. Effective interventions would be more easily replicated if they were explicitly described. Effectiveness might be more precisely demonstrated if more objective measures of physical activity and diet were used, and if the follow-up was over a longer period. International Journal of Obesity (2000) 24, 131-143

Behavior Therapy↗
PubMed2000

Non-penetrating chest blows and sudden death in the young.

Sudden death in the young after low energy anterior chest wall impact is an under-recognised phenomenon in this country. Review of the literature yields several American references to commotio cordis, mainly in the context of sporting events. Two cases are reported of sudden death in young men as a result of blunt impact anterior chest wall trauma. It is suggested that these cases draw attention to a lethal condition of which many practitioners are unaware.

Adolescent↗
PubMed2000

Training residents for community psychiatric practice: the resident perspective.

OBJECTIVE: To capture the views and experiences of psychiatry residents in 5 Canadian training programs with respect to community psychiatric training. METHOD: We sent a questionnaire regarding respondent demography, career interests, and community psychiatry training experiences to psychiatry residents at 5 training programs in Ontario. We undertook descriptive analyses and frequency comparisons on the returned data. RESULTS: The overall response rate was 48%, with considerable variation between programs. With respect to career planning, respondents indicated highest interest in urban hospital-based practice. An interest in additional community psychiatry training was, however, expressed, particularly by junior residents. Residents' suggestions for improving community psychiatry training included better promotion of training opportunities, improved quality of supervision in community settings, and more didactic teaching. CONCLUSION: Psychiatry residents are obtaining training experiences in community psychiatry, but objectives and guidelines are quite variable, as is reflected in their understanding of the definition of "community psychiatry." Residents' career paths are still focused on urban hospital-based practice or solo private practice, which likely reflects their prevalent training experiences. There is, however, interest in community psychiatry training. Junior residents may be more open to this type of practice, and curricula should allow more exposure to community psychiatry at this stage of training.

Adult↗
PubMed2000

A survey of aPTT reporting in Canadian medical laboratories. The need for increased standardization. Thrombosis Interest Group of Canada.

A survey of all licensed medical laboratories performing activated partial thromboplastin time (aPTT) testing in Canada was undertaken; the response rate was 50.7%. Preanalytic phase of testing seemed generally satisfactory, although 46% of laboratories were still using 3.8% or a 129-mmol/L concentration of citrate, and only 59% of institutions routinely performed testing to verify the platelet-poor status of the plasma used for aPTT testing. There were also concerns relating to the speed and duration of centrifugation for specimen preparation. While more than 67% of institutions had established an individual therapeutic range for aPTT testing, only 47% of laboratories verified this range with heparinized samples. Approximately 67% of the institutions that had verified the range had done this by spiking heparin concentrations into pooled plasma rather than using ex vivo specimens from patients receiving heparin therapy. There seemed to be a need for increased education about circumstances under which the therapeutic range should be rechecked and current standards for screening for the lupus anticoagulant. More than 71% of Canadian institutions surveyed used low-molecular-weight heparin, which may obviate many of the issues surrounding aPTT testing. Overall performance as documented by survey results seemed similar to that reported for the United States and Australasia.

Blood Specimen Collection↗
PubMed2000

A comparison of point-of-care instruments designed for monitoring oral anticoagulation with standard laboratory methods.

Our study compared point-of-care (POC) device monitoring with traditional clinical laboratory methods device of patients on oral anticoagulant therapy. The POC devices used in the study were Coumatrak, CoaguChek, CoaguChek Plus, Thrombolytic Assessment System (TAS) PT-One, TAS PTNC, TAS PT, Hemachron Jr. Signature, ProTime Microcoagulation System, and Medtronics ACT II. The clinical laboratory method used thromboplastins with different ISI values: Innovin and Thromboplastin C Plus (TPC). All POC INRs showed strong correlation with both laboratory methods, with correlation coefficients of >0.900. All POC methods demonstrated a significant (p <0.05) difference in INR values, except the TAS PTNC and ACT II INRs (p: 0.12 and 0.71 respectively) when compared with Innovin INRs. All POC INRs were significantly different from TPC generated INRs (p <0.05). Comparisons of the POC INRs to the group mean of the POC methods, show higher correlation (R>0.93), but there were still significant (p<0.05) differences noted between the POC group INR mean and CoaguChek Plus, ACT II, TAS PT-One, TAS PTNC, and Hemachron Jr Signature INRs. These data indicate that POC INR biases exist between laboratory methods and POC devices. Until a suitable whole blood INR standardization method is available, we conclude that clinicians using point-of-care anticoagulation monitoring should be aware of differences between POC and parent laboratory values.

Administration, Oral↗