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Biomedical subjects

F Mitchell

Publications and source records attributed to F Mitchell.

At least 37 records · Page 2Linked to original sources

Immunohistochemical distribution of neurons containing the G-proteins Gq alpha/G11 alpha in the adult rat brain.

A new class of G-proteins, the Gq family, has been recently identified and found to be involved in phospholipase C activation. The alpha subunits of the Gq and G11 members of this family are separate polypeptides but appear to have the same function. In this study, the cellular distribution in the adult rat brain of these G-proteins, Gq alpha/G11 alpha, was determined by immunohistochemistry using an antipeptide antiserum directed against the predicted C-terminal decapeptide which is conserved between these polypeptides. The specificity of the antiserum was verified by Western blot analysis using rat brain homogenates. Immunoreactivity was detected in neurons, where it was localized in the dendrites and at the periphery of the cell bodies. The staining was abundant in the dendrites of cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. Staining was also found in neurons in the olfactory bulb, minor and major islets of Calleja, anterior olfactory nuclei and piriform cortex; the different cortical areas especially in their superficial layers; caudate-putamen, accumbens and olfactory tubercle; lateral septum and amygdala; hippocampal CA2-4 sectors of Ammon's horn, dentate gyrus and hilus; hypothalamic supraoptic nucleus; cerebellar granular layer; colliculi and superficial layers of the dorsal horn of the spinal cord. In conclusion, the brain neuronal localizations of Gq alpha/G11 alpha match that of phospholipase C, 1,4,5-triphosphate receptor and, to a lesser extent 1,4,5-triphosphate-3-kinase.

Animals↗

Stimulus-response coupling in FMLP-stimulated U937 monocytes: effect of differentiation on Gi2 expression.

The effect of differentiation on FMLP-stimulated InsP production and G-protein expression was investigated in U937 monocytes. FMLP (0.01-10 microM) stimulated [3H]InsP production in dimethyl sulphoxide-differentiated, but not in immature, U937 cells. Ionomycin (1 and 10 microM) stimulated [3H]InsP production equally well in both cell types. The FMLP response was blocked by pertussis toxin (100 ng/ml for 4 h) which catalysed [32P]ADP ribosylation of a 40 kDa 'Gi-like' G-protein alpha subunit in these cells. This protein was also identified immunologically using anti-peptide antibodies that detect 'Gi-like' alpha subunits (SG2) or Gi2 alpha specifically (LE2). With LE2 a 5-fold increase in Gi2 alpha levels was seen following differentiation of the cells, suggesting that FMLP receptor expression is accompanied by an increase in the G-protein with which these receptors interact.

Adenosine Diphosphate Ribose↗

Protein kinase C--a family affair.

The structural analysis of protein kinase C has led to the identification of a family of related gene products. This family of kinases consists of six unique genes that give rise to at least seven polypeptides. The high degree of conservation and the differential distribution of these mRNAs/proteins suggest that they perform distinct functions in vivo. Characterization of the activities of some of these proteins in vitro shows that there are functional differences with respect to both their regulation and substrate specificity. This indicates that each member of this family may play a unique role in signal transduction.

Amino Acid Sequence↗

Investigations on the mechanism of liver tumour induction by peroxisome proliferators.

Further understanding of the mechanism by which peroxisome proliferators induce liver tumours is essential to assessing the risks of such compounds to exposed humans. To this end the effects of nafenopin upon the liver have been investigated. Nafenopin was shown to induce certain drug metabolising enzymes, but sub-cellular fractions from induced animals did not form reactive metabolites which could be detected as mutagens. Nafenopin treatment slightly increased the rate of alkaline elution of hepatic nuclear DNA from polycarbonate filters. However, simultaneous administration of sodium glycolate to stimulate H2O2 production or pyrazole to inhibit catalase activity had no further effects. These findings demonstrate that nafenopin is not activated to a mutagen and argue against the hypothesis that indirect DNA damage as a result of excess H2O2 production is responsible for tumour induction.

7-Alkoxycoumarin O-Dealkylase↗

Pew Memorial Trust policy synthesis: 3. Adolescent pregnancy: the responsibilities of policymakers.

In recent years, adolescent pregnancy and childbearing have emerged as major health and social policy issues, sparking debates in local and national forums. The concern is a response to rates of adolescent sexual activity, pregnancy, and out-of-wedlock childbirth that have risen sharply in the past 20 years. The deleterious effects of early parenthood, especially in poor communities, have been amply documented; education, future employment, and health status are among the areas affected. Efforts at intervention have ranged from preventing pregnancy by encouraging celibacy to trying to enhance the options available to those who are already parents. Many of these efforts have fallen short, proving unequal to the complexity of the issues being tackled. Relatively successful approaches have also been developed, however, and the synthesis describes several. Strategies addressing the needs of adolescents comprehensively and involving a multiplicity of concerned players appear to be most effective in the long term. There is a pressing need for more program documentation to substantiate this and other promising strategies.

Adolescent↗

A comparative study of a premature infant formula and preterm breast milk for low birthweight infants.

Although the unique composition of preterm milk (PTM) has led to its increasing use in feeding of low birthweight (LBW) infants, controversy exists as to whether such milk adequately meets their requirements. This study compares the clinical tolerance and anthropometric, biochemical and haematological parameters of LBW infants fed exclusively with their own mother's PTM, a premature infant formula (Alprem; Nestlé Australia) and a mixture of PTM and Alprem. Of 90 enrolled LBW infants (1000-1750 g birthweight), 78 completed the feeding trial for a mean duration of 42 days. Twenty-eight babies were fed Alprem (Group A), 31 received a mixture of Alprem and PTM (Group B) and 18 received PTM (Group C). Babies in Groups A and B were smaller, less mature and more asphyxiated at birth than those in Group C. Weight gain from full enteral feeding was greater in Group A (18.1 g/kg per day) and Group B (17.6 g/kg per day) than in Group C (13.0 g/kg per day). Throughout the trial, weight gain in Groups A and B exceeded predicted intra-uterine growth rates, whereas that for Group C approximated the predicted intra-uterine growth rates. Growth rates of length and head circumference were also greatest in the Alprem-fed babies. Infants receiving PTM were supplemented with calcium, sodium, vitamins and energy, whereas the only three infants requiring mineral supplementation in the Alprem group were those receiving Frusemide therapy for chronic lung disease. lower serum concentrations of phosphorus, iron, albumin and urea, and higher zinc and alkaline phosphatase concentrations were found in infants receiving PTM (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗

Steroid profiles and optimization of high-performance liquid chromatographic analytic procedure.

This paper presents a short review of the results obtained to date in our laboratory, with respect to the studies of steroid excretion profiles in both breast and endometrial cancer patients, by using gas-liquid chromatographic analysis. These data demonstrate the importance of minor estrogens, including catechol estrogens, and of their ratios with the classical ones, in studies of steroid metabolism in both breast and endometrial cancer. New data concerning postmenopausal endometrial cancer are consistent with our previous observations and demonstrate the necessity of measuring these steroids directly in tumors and examining patterns of metabolism in vitro. In order to analyze steroid metabolic patterns in vitro, however, high-performance liquid chromatography rather than gas-liquid chromatography methods are preferable on account of their selectivity, specificity, sensitivity and capacity to handle labile materials. With the aim of providing methods suitable for the complete resolution and analysis of these complex natural mixtures a method of computer-aided optimization of HPLC has been developed and its practical utility has been tested.

Adrenal Cortex Hormones↗

Solvent optimization of reversed-phase high-performance liquid chromatography for polar adrenal steroids using computer-predicted retentions.

Computer-aided optimization of a mobile phase has been applied to the isocratic reversed-phase separation of ten polar adrenocortical steroids, including aldosterone and reduced metabolites of cortisol and cortisone. A method based on a seven-step procedure for calculation of the Chromatographic Optimization Function (COF) has been used. Logarithmically transformed retention indices were used for computing multiple polynomial regressions for the retention times of compounds as a function of solvent composition, with the resultant COF as a dependent parameter used for selection of the better mobile phase. Peak crossovers and overlaps are accommodated in this method and the maximum acceptable analysis time factor is incorporated as well as weighting factors for priority separations. The utility of this procedure for complex mixtures of closely eluting compounds is discussed with respect to the Overlapping Resolution Map method and with the COF method of Glajch and Kirkland as used for automated optimization. Its application to aldosterone-containing samples from human adrenocortical tumours is illustrated.

Adrenal Cortex Hormones↗

There's no place like home.

Many children with chronic illness or handicapping conditions may not need continual or frequent institutional care, provided that suitable home care services are available. Yet, planning and experimentation with the concept of pediatric home care is just beginning on both the national and local levels and the concept of home care has yet to become widely understood and accepted. As a result, health planners and policy markers often fail to realize the potential advantage of home care to children, to families, and to society. Instead of seeing it as the most humane and effective way of caring for the chronically ill child, they see it as an increased financial burden. They also lack the perspective needed to realize that home care is ultimately the most cost-effective health care alternative, since it involves investing in people rather than in buildings or equipment. This report attempts to disseminate more widely the concept of home care by recounting a 2-year experience with a hospital-based pediatric home care service.

Child↗

Hospital energy management.

US hospitals are learning to deal with rising energy costs and uncertainties in the availability of energy supplies. Management responses to the challenge are affecting all aspects of design and operation.

Conservation of Energy Resources↗

Notes from the USA: 'new practitioners'.

In an effort to make primary care services more available in underserved areas, at reduced cost, the USA has supported the training of nurse practitioners and physician assistants. After ten years of struggle, clinic managers are beginning to understand and resolve some of the problems involved in employing these 'new practitioners.

Hospitals↗

Notes from the USA: fighting for survival.

Hospitals in the US face competition for patients. The hospitals are responding to this pressure by expanding into new primary care services and organisations. First in a new monthly series.

Economics, Hospital↗