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Biomedical subjects

M McIntyre

Publications and source records attributed to M McIntyre.

At least 19 recordsLinked to original sources
PubMed2000

Role of proteases in autolysis of Penicillium chrysogenum chemostat cultures in response to nutrient depletion.

An industrial strain of Penicillium chrysogenum was subjected to carbon or nitrogen limitation in a chemostat and the response monitored in terms of the "classical" indicators of autolysis (biomass decline and ammonia release), culture degradation (as measured by image analysis) and by obtaining profiles for three classes of proteases implicated in autolysis. Under both sets of conditions (carbon or nitrogen limitation), once started, autolysis involved a succession of different protease activities. The first stages of the process of autolysis in starved chemostat cultures was associated with peaks in the activities of both serine and aspartyl proteases, coinciding with the mobilisation of endogenous energy reserves. Conversely, a peak in the activity of metalloproteases was associated with the later stages of autolysis, perhaps occurring in response to depletion of endogenous energy reserves; the activity of these enzymes led to gross culture degradation, disintegration of ordered mycelial structures and signalled the end of metabolic activity (respiration) within the culture. These findings indicate that strategies intended to control/regulate autolysis in large-scale industrial fungal cultures might profitably be focused on regulation of the activity of key classes of proteases involved in the series of events leading to culture degradation.

Ammonia↗
PubMed1999

Differential expression of the cyclin-dependent kinase inhibitor P27 in primary hepatocytes in early-mid G1 and G1/S transitions.

P27, an inhibitor of cyclin-dependent kinases, plays an important role in the control of cell adhesion and contact inhibition-dependent cell cycle regulation. Hepatocytes, maintained in primary culture, offer a model of synchronized primary epithelial cells which retain a differentiated profile while stimulated to proliferate. We therefore investigated the pattern of endogenous p27 expression in cyclin rat hepatocytes isolated by collagenase perfusion followed by mitogenic stimulation. P27 was expressed in whole normal liver and freshly isolated hepatocytes. We then observed a sharp decrease in p27 levels, concomitant with the progression in early-mid G1, followed by reaccumulation in late G1 and the G1/S transition. Immunochemistry and BrdU labelling demonstrated nuclear localization of p27 and its expression in cells engaged in both G1 and S phase. P27 was detected in late G1 in complexes containing cyclins D1, E and A. Cyclin E- and A-associated kinase activities, however, were detected at the G1/S transition and depletion experiments confirmed that most active complexes were free of p27. Phosphorylated forms of p27 were detected in unstimulated and stimulated hepatocytes in both early-mid G1 and G1/S. Finally, two-dimensional gel electrophoresis showed evidence for several forms of p27 with a distinct profile of distribution in quiescent and stimulated hepatocytes. Collectively, our data offer a model in which p27 shows a biphasic profile of accumulation, with the early decrease possibly involved in the progression through early and mid G1. In contrast with most cell types tested so far, the late G1 accumulation did not impair formation of active cyclin E- and A associated kinases, and thus G1/S transition.

Animals↗
PubMed1999

Angiotropic large B-cell lymphoma with clinical features resembling subacute combined degeneration of the cord.

Angiotropic large cell lymphoma is a rare neoplastic disorder associated with a high mortality. The hallmark of the disease is lymphoid proliferation confined to the intravascular compartment without local tissue or vessel wall infiltration [1]. This feature is so striking that the disease was originally thought to arise from endothelial tissue and early cases were described as malignant angioendotheliomatosis. However, application of immunohistochemical methods for detection of lymphoid markers such as the CD45 and CD20 cell surface markers has confirmed its lymphoid origin, usually of B-cell lineage [2]. Clinical manifestations of the disease are protean and are due to multifocal medium and small vessel occlusion by tumour cells [3]. Characteristic sites of involvement are skin and central nervous system and although an ante-mortem diagnosis can be made from a biopsy specimen, it is often unsuspected [4]. We present a case of angiotropic large B-cell lymphoma in a 74-year-old man who presented with urinary symptoms and had a neurological picture resembling subacute combined degeneration of the cord.

Aged↗
PubMed1999

An intelligent framework for the classification of the 12-lead ECG.

An intelligent framework has been proposed to classify an unknown 12-Lead electrocardiogram into one of a possible number of mutually exclusive and combined diagnostic classes. The framework segregates the classification problem into a number of bi-dimensional classification problems, requiring individual bi-group classifiers for each individual diagnostic class. The bi-group classifiers were generated employing Neural Networks (NN), combined with a combination framework containing an Evidential Reasoning framework to accommodate for any conflicting situations between the bi-group classifiers. A number of different feature selection techniques were investigated with the aim of generating the most appropriate input vector for the bi-group classifiers. It was found that by reducing the original input feature vector, the generalisation ability of the classifiers, when exposed to unseen data, was enhanced and subsequently this reduced the computational requirements of the network itself. The entire framework was compared with a conventional approach to NN classification and a rule based classification approach. The framework attained a significantly higher level of classification in comparison with the other methods; 80.0% compared with 66.7% for the rule based technique and 68.00% for the conventional neural approach.

Computer Simulation↗
PubMed1999

Randomised comparison of electrode positions for cardioversion of atrial fibrillation.

OBJECTIVE: To compare the relative efficacy of anteroanterior v anteroposterior electrode pad positions for external cardioversion of atrial fibrillation. DESIGN: Prospective randomised trial. SETTING: Tertiary referral cardiology centre in the United Kingdom. PATIENTS: 90 patients undergoing elective cardioversion for atrial fibrillation. INTERVENTIONS: Cardioversion was attempted with self adhesive electrode pads with an area of 106 cm2 placed either in the anteroanterior (AA) or anteroposterior (AP) positions. Initial shock was 100 J which, if unsuccessful, was followed by 200 J, 300 J, and 360 J if required. Peak current and transthoracic impedance were measured. MAIN OUTCOME MEASURES: Cardioversion success rate and energy requirements. RESULTS: Cardioversion was successful in 81% of the patients (73/90). There was no statistically significant difference in the cardioversion success rate (AA 84%, 38/45 patients; AP 78%, 35/45 patients; p = 0.42) or mean (SD) energy requirement for all patients (AA 223 (96.1) J; AP 232 (110) J) or for patients who were successfully cardioverted (AA 197.9 (82.4) J; AP 195.4 (97.2) J; p = 0.9) between the two pad positions. The mean transthoracic impedance (TTI) for the first shock (AA 77.5 (18.4) ohms; AP 73.7 (18.7) ohms; p = 0.34) was not significantly different between the two groups. TTI correlated significantly with body mass index, percentage body fat, and chest AP diameter. There was a progressive decrease in TTI with serial shocks. While aetiology and TTI were the two independent significant predictive factors for energy requirement, duration of atrial fibrillation was the only independent predictor of cardioversion success in a multivariate analysis. CONCLUSIONS: Electrode pad position is not a determinant of cardioversion success rate or energy requirement.

Aged↗
PubMed1999

Superoxide anion production is increased in a model of genetic hypertension: role of the endothelium.

The hypothesis that the decreased nitric oxide (NO) availability observed in spontaneously hypertensive stroke-prone rats (SHRSP) is due to excess superoxide (O2-) was examined. O2- generation, measured by lucigenin chemiluminescence, was studied in 12- to 16-week male and female Wistar-Kyoto rats (WKY) and SHRSP. In addition, expression of the gene encoding endothelial NO synthase, the enzyme involved in NO generation, was investigated. O2- generation was increased in male and female SHRSP (4.11+/-0.24 and 3. 84+/-0.28 nmol O2-. min-1. mg-1 respectively) compared with their WKY counterparts and was significantly higher in male than female WKY (1.22+/-0.08 in males and 0.8+/-0.08 nmol O2-. min-1. mg-1 respectively) (SHRSP versus WKY P<0.0001, 95% CI -3.39, -2.51; male versus female WKY P=0.0029, 95% CI -0.67, -0.17). Removal of the endothelium by rubbing or addition of NO synthase inhibitors attenuated O2- generation in SHRSP but not WKY. In males, removal of the endothelium reduced O2- generation from 3.86+/-0.12 to 1.35+/-0. 08 nmol. min-1. mg-1 (P<0.0001, 95% CI 2.29, 2.81), whereas addition of L-NAME caused a reduction from 4.13+/-0.17 to 1.32+/-0.16 nmol. min-1. mg-1 (P<0.0001, 95% CI 2.36, 2.83). Similar reductions were observed in females. L-arginine had no significant effect, but tetrahydrobiopterin significantly decreased O2- generation in SHRSP from 4.04+/-0.11 to 2.36+/-0.40 nmol. min-1. mg-1 (P=0.0026, 95% CI 0.89, 2.44). Endothelial NO synthase mRNA expression was significantly greater in SHRSP than in WKY and in WKY males than in WKY females. These results show that O2- generation is increased in SHRSP and that the tissue and enzymatic sources of this excess O2- appear to be the endothelium and eNOS, respectively. The increase in O2- generation could explain the decreased availability of basal NO observed in this model of genetic hypertension.

Animals↗
PubMed1999

Endothelial function in hypertension: the role of superoxide anion.

Much attention has been focused on the role of nitric oxide in hypertension and cardiovascular disease. More recently, the role of superoxide anion and its interaction with nitric oxide has been investigated in this context. This review will concentrate on the role of superoxide in human and experimental hypertension, paying particular attention to the potential sources of superoxide within the vasculature and discussing some of the molecular mechanisms surrounding its production and dismutation. We discuss what is known about the human superoxide dismutase enzymes. We conclude that the balance between nitric oxide and superoxide is more important than the absolute levels of either alone.

Animals↗
PubMed1998

Hepatic regeneration in the isolated perfused rat liver followed by liver transplantation.

Controlling the S phase of the hepatocyte cell cycle would be of considerable help for stable retroviral foreign gene transfer. The aim of this article is to study hepatocyte regeneration during S phase in isolated, perfused rat liver followed by liver transplantation. Normal livers (G I: n = 7) were perfused with blood from normal rats for 6.1+/-0.3 hours. Regenerating livers (G II; n = 7) obtained 18 hours after partial hepatectomy were perfused for 6.0+/-0.3 hours with blood from rats partially hepatectomized 18 hours before. Regenerating livers (G III; n = 7) obtained 22 hours after partial hepatectomy were perfused for 2.4+/-0.1 hours with blood from normal rats. In the normothermal perfusion system, a bolus of 25 mg of 5-bromo-2'-deoxyuridine (BrdU) was added to the perfusate. Liver biopsies were taken at the end of each experiment. In group II, a biopsy was also taken 1 hour after BrdU introduction. At the end of each experiment, livers were orthotopically transplanted. The percentage of BrdU positive hepatocyte nuclei was 0.2% in G I; 14.8% and 38.4% after 1 hour and 6.1 hours, respectively, in G II; and 46.5% after 2.4 hours in G III. In G I, five rats died at day 1, 5, 6, 7, and 48 and two rats were still alive after 17 months. In G II, all the rats died before day five. In G III, two rats died at day one, one at day six, and four were still alive after 12 months. This study shows that, after 6 hours of normothermal perfusion, organ viability allows successful liver transplantation and that rat hepatocyte regeneration during cell cycle S phase in isolated normothermal conditions progresses in a similar way-quantity and timing-to liver regeneration found in vivo after partial hepatectomy.

Animals↗
PubMed1998

Morphogenetic and biochemical effects of dissolved carbon dioxide on filamentous fungi in submerged cultivation.

The inhibitory effects of elevated CO2 in submerged fermentation processes involving bacteria and yeasts have been extensively examined. However, until recently, there have been few similar studies involving filamentous fungi, despite the economic importance of this group of organisms. Many of the investigations that have been carried out have involved inappropriate simulation methods and, as a result, may have overestimated the morphogenetic and biochemical effects of elevated CO2 on filamentous fungi. Recent studies, involving continuous culture of Aspergillus niger and the use of computerised image analysis systems, have allowed a more detailed and accurate description of elevated CO2 inhibition and quantification of the subtler morphogenetic effects. A critical evaluation of the various experimental methods that have been used to simulate, at laboratory scale, what is assumed to occur in large-scale bioreactors is necessary. The review of simulation methods employed has much broader relevance to many other microbial and cell culture systems, emphasising the need to think about the appropriateness and relevance of experimental design.

Carbon Dioxide↗
PubMed1998

Computerised electrocardiology employing bi-group neural networks.

A configuration of bi-group neural networks (BGNN) is proposed combined with an evidential reasoning framework to interpret 12-lead electrocardiograms for three mutually exclusive classes. A number of pre-processing feature selection techniques were investigated prior to application of the input feature vector to each individual BGNN. The network outputs were discounted within a belief interval of 1 based on their performance on test data prior to combination. It was found that the application of the feature selection techniques enhanced the individual performance of the BGNN, and subsequently enhanced the overall performance. The proposed framework was compared with conventional classification techniques of multi-output neural networks and linear multiple regression. The framework attained a higher level of classification in comparison with the other methods; 70.4% compared with 66.7% for both multi-output neural and statistical techniques.

Diagnosis, Differential↗
PubMed1998

Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

Actins↗
PubMed1998

Issues in the implementation of cancer staging in Canada.

All sectors of the cancer control community in Canada agree that cancer staging is useful, and that stage should be assigned to every new case. At present, however, staging is not always recorded in the patient's records and treatment patterns and outcomes are rarely reported in terms of stage. This paper discusses what needs to be done to promote the use of staging in Canada. It is concluded that multifaceted programs of interventional continuing education (CE), tailored to meet the needs of the particular institution, offer the best prospect of success but the necessary organizational structure and information systems have to be put into place in advance. Implementation programs should be based on a thorough evaluation of the particular needs of the institution or community, and should be evaluated carefully in a few institutions before an attempt is made to disseminate them more widely. We recommend a phased approach to implementation which will first target institutions that already have the necessary infrastructure, i.e., provincial cancer centres. Demonstration of the feasibility and value of staging in that setting is seen as a means of promoting the adoption of staging in other institutions.

Academies and Institutes↗