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Biomedical subjects

M Maxwell

Publications and source records attributed to M Maxwell.

At least 19 recordsLinked to original sources
PubMed1992

Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry.

These studies demonstrate the expression of IGF-1, IGF-11, and their respective receptor mRNAs in primary human astrocytomas and meningiomas. In situ hybridization and immunocytochemistry have localized a strong expression of both IGF-1 and IGF-11 mRNAs and of their protein products in the tumor cells of astrocytomas and meningiomas. The expression of IGF-1 and IGF-11 mRNAs in the tumor cells was accompanied by the co-expression of their respective type-1 and type-11 IGF receptor mRNAs. Control, non-malignant human brain expressed IGF-1 mRNA and IGF-1 and IGF-11 receptor mRNAs. There was no significant expression of IGF-11 MRNA in the control brain specimens. Control pachymeninges (dura mater) expressed low levels of IGF-1 mRNA and IGF-1 receptor mRNA. There was no significant expression of IGF-11 and IGF-11 receptor mRNAs in pachymeninges. The co-expression of IGFs and their receptors in brain tumors may contribute in their development and maintenance. The strong inappropriate expression of IGF-11 mRNA and its protein product in the tumor cells of astrocytomas and meningiomas, but not in normal brain specimens, may serve as molecular markers for the early detection of these tumors.

Astrocytoma↗
PubMed1992

Effect of the expression of transforming growth factor-beta 2 in primary human glioblastomas on immunosuppression and loss of immune surveillance.

Glioblastomas are malignant brain tumors that are attended by an immunosuppressed state. The authors have studied the expression of transforming growth factor-beta 2, which is known to have potent immunosuppressive and angiogenic properties. Transforming growth factor-beta 2 messenger ribonucleic acid and its protein product are both found to be greatly overexpressed in these tumors and are absent from normal brain tissue. The overexpression of this growth factor may contribute to the escape of neoplastic astrocytes from immune surveillance and, furthermore, to the immunosuppressed state that is characteristic of many of these patients.

Astrocytoma↗
PubMed1992

The chief scientist reports ... The Scottish general practice shadow fund-holding project--outline of an evaluation.

After the agreement in January 1989 between the Minister of Health at the Scottish Office, Mr Michael Forsyth, and six groups of General Practitioners (GPs) in the Grampian and Tayside Regions of Scotland to embark on a 'shadow fund-holding' project, the Government agreed to promote an independent evaluation of the scheme. As a result, the Department of General Practice at Edinburgh University was invited to present plans to evaluate the working of and results of the scheme. Consultations with the Minister and Health Department officials, the general practices concerned, and staff of the two Health Boards involved took place during the first three months of 1990, and an outline protocol for the evaluation was approved and funded through the Chief Scientist Organisation for a three-year period from April 1990. It was agreed by all involved that piecemeal publications of results during the period of the research would be inappropriate, but with other attempts to evaluate fund-holding now being reported elsewhere in the UK, it has been agreed that an outline of issues being explored and the methods being used would be in the general interest. This paper first outlines the principal areas in which the evaluation is being focused, then describes the general methods being used, and finally comments on some of the problems encountered with the evaluation. The project should be seen as a descriptive beginning to what may well be a period of around a decade needed to appreciate the full implications of any major change in the organisation of health service provision.

Family Practice↗
PubMed1991

Case-control study of leukaemia and non-Hodgkin's lymphoma in children in Caithness near the Dounreay nuclear installation.

OBJECTIVE: To examine whether the observed excess of childhood leukaemia and non-Hodgkin's lymphoma in the area around the Dounreay nuclear installation is associated with established risk factors, or with factors related to the plant, or with parental occupation in the nuclear industry. DESIGN: Case-control study. SETTING: Caithness local government district. SUBJECTS: 14 cases of leukaemia and non-Hodgkin's lymphoma occurring in children aged under 15 years diagnosed in the area between 1970 and 1986 and 55 controls matched for sex, date of birth, and area of residence within Caithness at time of birth. MAIN OUTCOME MEASURES: Antenatal abdominal x ray examination; drugs taken and viral infections during pregnancy; father's occupation; father's employment at Dounreay and radiation dose; distance of usual residence from the path of microwave beams, preconceptional exposure to non-ionising radiation in the father; and other lifestyle factors. RESULTS: No raised relative risks were found for prenatal exposure to x rays, social class of parents, employment at Dounreay before conception or diagnosis, father's dose of ionising radiation before conception, or child's residence within 50 m of the path of microwave transmission beams. Results also proved negative for all lifestyle factors except an apparent association with use of beaches within 25 km of Dounreay. However, this result was based on small numbers, arose in the context of multiple hypothesis testing, and is certainly vulnerable to possible systematic bias. CONCLUSION: The raised incidence of childhood leukaemia and non-Hodgkin's lymphoma around Dounreay cannot be explained by paternal occupation at Dounreay or by paternal exposure to external ionising radiation before conception. The observation of an apparent association between the use of beaches around Dounreay and the development of childhood leukaemia and non-Hodgkin's lymphoma might be an artefact of multiple testing and influenced by recall bias.

Case-Control Studies↗
PubMed1991

Expression of angiogenic growth factor genes in primary human astrocytomas may contribute to their growth and progression.

Astrocytomas are highly malignant brain tumors and are among the most neovascularized solid tumors. We have investigated the expression of the angiogenic growth factors acidic fibroblast growth factor and transforming growth factor-alpha, together with its receptor epidermal growth factor receptor, in 30 primary astrocytomas. Both acidic fibroblast growth factor and transforming growth factor-alpha, together with epidermal growth factor receptor, are found to be greatly overexpressed in these tumors when compared with normal brain. This overexpression of angiogenic growth factors may underlie the intense neovascularization characteristic of astrocytomas.

Angiogenesis Inducing Agents↗
PubMed1991

Coronary vasoconstriction induced by vasopressin. Production of myocardial ischemia in dogs by constriction of nondiseased small vessels.

BACKGROUND: We studied the effect of intracoronary administration of arginine-8-vasopressin on blood flow in nondiseased coronary arteries and determined whether this vasoconstriction was severe enough to produce ischemia in 30 dogs. METHODS AND RESULTS: In group 1 (n = 6), after vasopressin administration coronary blood flow was decreased by 41% (p less than 0.002) without changes in heart rate or aortic pressure, and left ventricular ejection fraction measured by radionuclide angiocardiography was decreased by 18% (p less than 0.0005). In group 2 (n = 6), ischemia was confirmed by measurement of transmural pH changes. Administration of vasopressin decreased subendocardial pH of the infused zone from 7.40 +/- 0.03 to 7.31 +/- 0.07 (p less than 0.01). The subendocardial pH of the zone not infused with vasopressin did not change. To overcome the intrinsic regulation of blood flow, operating primarily in small coronary arteries, we hypothesized that vasopressin must increase resistance primarily in large rather than small coronary arteries. After intracoronary infusion in group 3 (n = 6), however, most (94%) of the increase in resistance during vasopressin administration was explained by an increase of resistance in small coronary arteries. In group 4 (n = 9), vasopressin decreased coronary blood flow by 50% and decreased local shortening by 90% at a time when systemic hemodynamics were unchanged. Coronary constriction induced by vasopressin, or the recovery from it, also was not altered by cyclooxygenase blockade. CONCLUSIONS: Thus, vasopressin produces myocardial ischemia by constricting small, nondiseased coronary arteries severely enough to overcome the competition from normal coronary regulation, and this ischemic event is not mediated by prostaglandin products.

Animals↗
PubMed1991

An evaluation of communication skills training for physiotherapy students.

This evaluation study concerned the modules of communication skills training in the second, third and fourth years of an undergraduate programme of study in an honours degree course in physiotherapy. Questionnaires were administered to the students to ascertain their attitudes to the training programme. Lecturers in physiotherapy who were not involved in the training programme were interviewed regarding their perceptions of the importance of this communication skills training. The results show a positive attitude towards the skills training, and the important relationship with good clinical practice was emphasized.

Attitude↗
PubMed1990

Human meningiomas co-express platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products.

The present studies investigated the expression of the platelet-derived growth factor (PDGF) and PDGF-receptor genes in human meningiomas. Northern blot analysis demonstrated that all meningiomas examined expressed both the c-sis/PDGF-2 proto-oncogene and the PDGF-receptor gene. In situ hybridization localized the c-sis mRNA and the PDGF-receptor mRNA in the tumor cells of the meningioma tissues. Control pachymeninges derived from adult individuals, without meningiomas, expressed only PDGF-receptor mRNA but not the c-sis mRNA. Immunocytochemistry studies detected both the c-sis and the PDGF-receptor protein products in meningioma tissues but only the PDGF-receptor protein products in control pachymeninges. These findings indicate the presence of an autocrine mechanism in human meningiomas based on the co-expression of the c-sis/PDGF-2 proto-oncogene and PDGF-receptor gene and their protein products. This co-expression of a potent mitogen and its receptor may contribute to the growth and maintenance of human meningiomas.

Blotting, Northern↗
PubMed1990

A procedure for reducing errors in reports of life events.

Despite the widespread use of life event inventories, relatively little research has been conducted evaluating whether recall techniques can reduce reporting errors. This study evaluated whether memory aids would reduce errors in reports of life events and explored subjects' explanations for why they had given inconsistent answers to life event questions over the course of two interviews. Seventy-one college students were randomly assigned to two groups: memory aids (MA: n = 36) and no memory aids (NMA: n = 35). Memory aids, as used in this study, reduced errors in reports of life events as reflected in the following results: (1) significantly fewer subjects in the MA group reported dating events incorrectly; (2) subjects in the MA group consistently gave more reliable responses between the two interviews as measured by intraclass correlations; (3) there was a significantly higher test-retest reliability correlation for life events reported by MA subjects; and, (4) MA subjects recalled more life events and had fewer inconsistent responses. A further probe revealed that memory aids differentially aided recall of subjective as compared to objective life events. Overall, the findings of this study suggest that memory aid procedures can differentially reduce errors in reporting life events.

Adult↗
PubMed1990

Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance.

The present studies investigated the expression of the two PDGF genes (c-sis/PDGF-2 and PDGF-1) and the PDGF-receptor b gene (PDGF-R) in 34 primary human astrocytomas. Northern blot analysis demonstrated the coexpression of the c-sis/PDGF-2 protooncogene and the PDGF-R gene in all astrocytomas examined. The majority of the tumors also expressed the PDGF-1 gene. There was no correlation between the expression of the two PDGF genes. Nonmalignant human brain tissue expressed the PDGF-R and PDGF-1 genes but not the c-sis/PDGF-2 protooncogene. In situ hybridization of astrocytoma tissue localized the expression of the c-sis and PDGF-R mRNA's in tumor cells. Capillary endothelial cells also expressed c-sis mRNA. In contrast, nonmalignant human brain tissue expressed only PDGF-R mRNA but not c-sis/PDGF-2 mRNA. The coexpression of a potent mitogenic growth factor protooncogene (c-sis) and its receptor gene in astrocytoma tumor cells suggests the presence of an autocrine mechanism that may contribute to the development and maintenance of astrocytomas. The expression of c-sis mRNA in tumor cells but not in nonmalignant brain cells may serve as an additional diagnostic criterion for the detection of astrocytomas in small tissue specimen using in situ hybridization for the detection of c-sis mRNA and/or immunostaining for the recognition of its protein product.

Astrocytoma↗
PubMed1990

Platelet-derived growth factor in idiopathic pulmonary fibrosis.

Fibrosis is a complex process involving an inflammatory reaction, fibroblast proliferation, and abnormal accumulation of interstitial collagens. Mononuclear cells are usually present in lung fibrosis. Activated monocytes and macrophages in culture have been shown to produce several growth factors including platelet-derived growth factor (PDGF). PDGF is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells and a stimulator of collagen synthesis. We have studied the expression of c-sis/PDGF-2 mRNA in lung tissues derived from five patients with idiopathic pulmonary fibrosis (IPF) and from four control individuals without IPF. Northern blot analysis of specimens obtained from four patients with IPF revealed the expression of the c-sis/PDGF-2 protooncogene. A control lung tissue without IPF did not express the c-sis protooncogene. In situ hybridization extended these studies demonstrating the expression of the c-sis mRNA in the five specimens with IPF but not in the four control specimens without IPF. The expression of c-sis mRNA was localized primarily in the epithelial cells. Invading alveolar macrophages also expressed c-sis mRNA. The expression of c-sis mRNA was accompanied by the expression of PDGF-like proteins in lung specimens with IPF but not in control lung specimens. These findings demonstrate the in vivo expression of the c-sis/PDGF-2 protooncogene and the production of PDGF-like proteins in the epithelial cells and macrophages of the fibrotic tissue. This localized and sustained production of PDGF-like mitogen may constitute an important contributing factor in the abnormal fibroblast proliferation and collagen production, events associated with pulmonary fibrosis.

Collagen↗
PubMed1990

Precocious puberty following head injury. Case report.

A 6-year-old girl developed secondary sexual characteristics 5 months after severe closed head injury. Endocrinological tests confirmed a pubertal sexual condition; there was also diminution of serum melatonin and disruption of the diurnal pattern. Magnetic resonance imaging demonstrated focal hypothalamic injury; this is believed to be the first time such a posttraumatic lesion has been demonstrated by imaging techniques. The pathophysiology of this condition is discussed.

Brain Stem↗
PubMed1990

Gastric paraganglioma: an immunohistological and ultrastructural case study.

This is a report of the immunohistochemical and ultrastructural features of a case of paraganglioma of the stomach in a 61-year-old woman who presented with melaena. The typical 'Zellballen' arrangement of epithelial cells with granular cytoplasm was present and the tumour was highly vascular. The polygonal epithelial cells stained strongly for neuron specific enolase and the intervening elongated sustentacular or support cells were positive for S100 protein and vimentin. Many dense core granules were present within the epithelial cells while the elongated support cells contained plentiful diffuse intermediate filaments. No hybrid cells or ganglion cells were present in the tumour. This is the sixth recorded case of gastric paraganglioma and the first to be studied in detail by immunostaining and electron microscopy.

Female↗
PubMed1989

Localization and regulation of vasopressin mRNA in human neurons.

Vasopressin (prepropressophysin) mRNA is detected in neurons of the supraoptic, suprachiasmatic, and paraventricular nuclei of human postmortem hypothalamic specimens by quantitated in situ hybridization using 35S-labeled single-stranded cDNA probes directed against exon C of the human vasopressin gene. This hybridization displays the anticipated anatomic distribution, as well as several biochemical features supporting its specificity. Hybridization densities in supraoptic neurons, a measure of vasopressin gene expression, display substantial variability from brain-to-brain. We can attribute much of this brain-to-brain variability to differences in antemortem extracellular volume status. This conclusion is based on a) animal models of the human postmortem process, b) animal models of common agonal events, c) good correlations between antemortem volume status and neuronal vasopressin mRNA hybridization densities in human postmortem specimens matched for age and postmortem interval, and d) our inability to correlate human neuronal vasopressin mRNA hybridization densities with other clinical and postmortem features. These results provide an example of antemortem regulation of a human neuroendocrine gene using postmortem tissue.

Aged↗
PubMed1989

Neuropeptide-Y. A peptide found in human coronary arteries constricts primarily small coronary arteries to produce myocardial ischemia in dogs.

Neuropeptide-Y (NPY), a brain peptide, is located in the walls of human coronary arteries. This study assessed the effects of NPY on the coronary circulation in 40 chloralose-anesthetized, open-chest dogs. Intracoronary NPY (42 nmol over 5.2 min) caused a 39% reduction in coronary blood flow without changing heart rate or aortic pressure. To determine whether this vasoconstriction could produce ischemia, intramyocardial pH was measured in seven dogs (group I) and decreased from 7.45 +/- 0.06 to 7.37 +/- 0.06 pH units after NPY in the subendocardium (P less than 0.0002), and from 7.45 +/- 0.06 to 7.40 +/- 0.05 pH units (P less than 0.04) in the subepicardium of the infused zone. Left ventricular ejection fraction (LVEF), measured by radionuclide angiography, decreased from 0.52 +/- 0.08 to 0.42 +/- 0.12 U (n = 5, P less than 0.01) during NPY. NPY-induced vasoconstriction was also associated with ST-T wave changes on the electrocardiogram (ECG) in eight of nine other animals (group V). In another group of six dogs (group IV), the change in small vessel resistance accounted for 94% of the increase in total resistance, so that the primary vasoconstrictor effect of NPY was exerted on small coronary arteries. Thus, NPY, a peptide found in human coronary arteries, caused constriction of primarily small coronary arteries that was severe enough to produce myocardial ischemia as determined by ECG ST-T wave changes, and decreases in intramyocardial pH and LVEF in dogs.

Animals↗
PubMed1988

Antihypertensive drug side effects in the Hypertension Detection and Follow-up Program.

The 5485 participants in the Hypertension Detection and Follow-up Program, Stepped-Care group form one of the largest groups to date on which detailed surveillance of long-term antihypertensive therapy and drug side effects has been reported. During a 5-year period, among all hypertensive persons (mild, moderate, and severe combined) who were not taking antihypertensive medications at the beginning of the study and who attended the clinic at least once during the 5-year trial, a total of 9.3% had definite or probable side effects severe enough to cause discontinuation of the drug treatment in question. Less than 1% of active participants required hospitalization for side effects. No death that could be attributed to side effects was detected. Thus, the Hypertension Detection and Follow-up Program data, which have previously demonstrated the beneficial effects of antihypertensive therapy, confirm the relative safety of such therapy.

Adult↗
PubMed1987

Induction of cellular transglutaminase biosynthesis by sodium butyrate.

Cellular transglutaminase activity was induced in simian virus-transformed human embryonic lung fibroblasts (WI-38 VA13A) by sodium butyrate. The level of enzyme activity approached a maximum by 6 days; 9-11-fold higher in the presence of sodium butyrate (1 mM) than in its absence. The observed increases in cellular transglutaminase activity could be entirely accounted for by equivalent increases in the levels of enzyme protein measured by inhibition enzyme-linked immunosorbent assay. Sodium butyrate also increased the rate of enzyme synthesis, but had no effect on the rate of cellular transglutaminase degradation. The increase in the rate of enzyme synthesis was matched by an increased level of translatable transglutaminase mRNA as measured in a cell-free translation system. Our results suggest that sodium butyrate regulates cellular transglutaminase at the pretranslational level.

Antibodies, Monoclonal↗