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Biomedical subjects

M Ingram

Publications and source records attributed to M Ingram.

At least 37 records · Page 2Linked to original sources
PubMed1996

11 beta-Hydroxylase activity in glucocorticoid suppressible hyperaldosteronism: lessons for essential hypertension?

Corticosteroid 11 beta-hydroxylation is catalysed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and in patients with Conn's syndrome. Based on both 11-deoxycortisol:cortisol (S:F) and 11-deoxycorticosterone:corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate-limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimaeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone and DOC concentrations, appeared to be more sensitive to ACTH in GSH than the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in the condition, and may contribute to the phenotypic variability.

Adrenocorticotropic Hormone↗
PubMed1996

Corticosteroids in essential hypertension: multiple candidate loci and phenotypic variation.

1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function. 2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics. 3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11 beta-hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine. 4. The genes encoding 11 beta-hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5' regulatory regions from 11 beta-hydroxylase and 3' coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition. 5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11-deoxycortisol/cortisol, consistent with reduced activity of 11 beta-hydroxylase in the zona fasciculata. 6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, remain to be studied.

Adrenal Cortex Hormones↗
PubMed1994

An epidemiologic approach to predictors of elective coronary artery bypass mortality in a non-university hospital population.

This investigation was undertaken to determine whether perioperative variables present in patients scheduled for elective coronary artery bypass grafting (CABG) surgery, and documented in earlier studies at university programs, bear any significant relationship to mortality occurring in a population of prospectively monitored non-university hospital patients. The investigation sought to identify the risk factors that might be present in these patients. Toward this purpose, data from 1,095 patients having CABG surgery at four major non-university Pittsburgh hospitals were analyzed using univariate and multivariate analysis to develop a model for predicting survival. From this model, three variables, unstable angina or recent myocardial infarction (< 6 weeks); evidence of chronic heart failure at the time of the preoperative examination; and greater than 65 years of age were found to have high statistical significance (P < 0.02) in predicting mortality in this non-university-hospital population. In summary, the study demonstrated that three variables, previously confirmed as being valuable predictors of risk in university hospital populations, also have significant predictive value in elective non-university CABG survival.

Aged↗
PubMed1993

Human recombinant interleukin-1 beta-mediated growth inhibition of cultured malignant glioma cells.

The effect of human recombinant interleukin-1 beta (hrIL-1 beta) on tumor growth was studied in eight glioma cell lines. hrIL-1 beta inhibited growth in all cell lines, but to varying extents. Two cell lines were suppressed by 0.5 ng/ml hrIL-1 beta, and three cell lines required 20 ng/ml. hrIL-1 beta also induced morphological changes and increased F-actin contents. hrIL-1 beta-treated cells demonstrated multipolar shapes and numerous processes with a greater number of cell-cell contacts 24 hours after treatment. Fluorescence microscopy revealed that these processes contained a large amount of polymerized F-actin. These results suggest that hrIL-1 beta-mediated growth inhibition may be related to the differentiation of glioma cells.

Brain Neoplasms↗
PubMed1992

Cytokine production from freshly harvested human mononuclear cells attached to plastic beads.

The release of tumor necrosis factor (TNF), interleukin-1 beta (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) from freshly harvested monocytes and lymphocytes attached to plastic beads was investigated. Previous studies had shown that freshly harvested endothelial cells attached to microcarrier beads release an endothelium-derived relaxing factor. Attachment of freshly harvested lymphocytes and monocytes to plastic beads created a dense network, consisting of 25% monocytes and 75% lymphocytes as shown by flow cytometry. Viability of cells was 90%. Monocytes were characterized by phagocytosis and non-specific esterase stain. Freshly harvested cells stimulated with lipoprotein lipase (LPS) released TNF and IL-1. Non-stimulated cells also produced GM-CSF five hours after collection of blood.

Cell Aggregation↗
PubMed1990

The CT scanner as a therapy machine.

Many tumors in the brain and in other tissues can be delineated precisely in images obtained with a CT scanner. After the scan is obtained the patient is taken to another room for radiation therapy and is positioned in the beam with the aid of external markers, simulators or stereotactic devices. This procedure is time consuming and subject to error when precise localization of the beam is desired. The CT scanner itself, with the addition of a collimator, is capable of delivering radiation therapy with great precision without the need for external markers. The patient can be scanned and treated on the same table, the isocenter of the beam can be placed precisely in the center of the lesion, the beam can be restricted to just those planes in which the lesion appears several arcs can be obtained by simply tilting the gantry, and the position of the patient in the beam can be monitored continuously during therapy. We describe here the properties of the CTX, the CT scanner modified for therapy.

Animals↗
PubMed1990

Immunotherapy for recurrent malignant glioma: an interim report on survival.

We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

Adult↗