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Biomedical subjects

W Barker

Publications and source records attributed to W Barker.

18 recordsLinked to original sources

Temperature enhancement of syncytium formation by HIV and Sendai virus.

Syncytium formation, the characteristic cytopathic effect (CPE) of the human immunodeficiency virus (HIV) and cell fusion by Sendai virus, is accelerated by increasing the ambient temperature to values at which normal metabolic activity is inhibited. Uninfected C8166, CEM, and H9 cells were absorbed at 4 degrees C onto monolayers of H9 cells chronically infected with HIV and incubated subsequently at either 37 degrees C or 45 degrees C. Similarly chick and human erythrocytes and Hela cells were agglutinated with Sendai virus at 4 degrees C before incubation at temperatures of up to 50 degrees C. With both viruses the rate of cell fusion was directly related to temperature. Since membrane fluidity is dependent on the phase-transition temperature points of the membrane lipids it is proposed that sufficient membrane fluidity is essential for cell fusion to occur. The implication of these observations on the cytopathology of HIV is discussed.

Cell Fusion

Health visiting: action research in a controlled environment.

The nature of health visiting is discussed. It operates in a radically different way from any of the curative services. Research into the effectiveness of health visiting must therefore take into account the many differences in context, in professional goals and in the nature of the interaction between health visitors and their "clients", compared with the work of the curative professions within their more controlled and controlling environments. The evaluation of one large scale health visitor intervention study is used here to highlight these differences. Health visiting research needs to free itself from the attempts by some to apply the laboratory model of evaluation, if it is to develop a corpus of "action research" thinking which reflects its more human and developmental characteristics.

Child

Manipulation of body fat composition with sterculic acid can inhibit mammary carcinomas in vivo.

Sterculic acid, a delta-9-desaturase inhibitor, administered to rats caused a rise in the stearic:oleic acid ratio of total lipids in peripheral red cells, serum and liver (P less than 0.001). As a reduction in the stearic:oleic acid ratio has been described in cancer cells, we investigated the effect of sterculic acid on tumour growth. Female F344 rats were injected subcutaneously with two different doses of sterculic acid for 4 weeks prior to, and 4 weeks following, implantation of a nitrosomethylurea-induced mammary tumour. Tumour growth was inhibited equally by the two doses of sterculic acid (P less than 0.001). A rise in the stearic:oleic acid ratio of tumours was observed in rats treated for only 16 days with sterculic acid. Manipulation of the tissue stearic:oleic acid ratio inhibits transplanted mammary tumour growth in rats.

Adipose Tissue

Syncytia formation in HIV-1 infected cells is associated with an increase in cellular oleic acid.

Infection of cells with the human immunodeficiency virus type-1 (HIV-1) usually results in the formation of giant multinuclear cells (syncytia) [(1986) Nature 322, 470-474; (1986) Nature 322, 725-728; (1985) Hum. Pathol. 18, 760-765; (1987) Ann. Neurol. 21, 490-496]. The appearance of syncytia is associated with an increase in the monounsaturated oleic acid content. This report describes experiments which compare the activity of known antiviral agents with that of saturated fatty acid derivatives in inhibiting oleic acid and syncytia formation. A concept is introduced which proposes that infection of cells with the human immunodeficiency virus causes a rise in cellular oleic acid which leads to increased membrane fluidity.

Cell Line

Sensitivity and specificity of positron emission tomography and magnetic resonance imaging studies in Alzheimer's disease and multi-infarct dementia.

Positron emission tomographic (PET) scans using [18F]-fluorodeoxyglucose and magnetic resonance imaging (MRI) scans were quantitatively analyzed for metabolic and structural abnormalities in normal subjects and patients classified as having Alzheimer's disease (AD), mixed dementia and multi-infarct dementia (MID) according to Hachinski ischemic scores. MRI-detected abnormalities in the periventricular white matter and in subcortical locations increased in incidence with age in normals and increased markedly in AD and especially in MID. Upper limits for the severity of these white matter lesions could be defined only for normal young and elderly subjects, but not for AD, mixed or MID patients. PET scan abnormalities occurred in about 90% of demented patients and in 54% of elderly and 34% of young normals. There was no characteristic pattern of abnormality that distinguished MID from AD patients. It is concluded that PET and MRI studies in demented patients are useful ancillary tests especially in evaluating the mild, questionably demented subject and for assessing the functional impact of structural disease.

Aged

Two behavioral states studied in a single PET/FDG procedure: error analysis.

In a previous publication the theory, procedure, and results of a method were described for making two sequential measurements of cerebral metabolic rate for glucose (CMRglc), within a 2-hr period, using [18F]fluorodeoxyglucose. The error that is specific to this technique was estimated using computer simulations. CMRglc for the second state was sensitive to errors in (a) the values of the rate constants, (b) alignment of PET slices between the two scans, and (c) subtraction of one PET image from another. The root mean square of the average error from each error source was 6.4%, which gives the theoretical reliability of this method. The measured reproducibility, taken from our previous publication, was 4.2-6.2%, which is in good agreement with the present result. This method contributes a small additional error above that expected for two independent scans. However, independent scans done on different days are likely to be subject to larger physiological variations in CMRglc than would occur using this method.

Brain

Natural IFN-alpha therapy in hairy-cell leukaemia (namalva-type IFN--Wellferon).

More than 50 patients with hairy-cell leukaemia have now been entered into the British Wellferon (IFN) study, at different centres under the coordination of the Wellcome Research Laboratories. While the treatment duration and dosage varied between patients, the initial dose was usually 3 megaunits daily by intramuscular or subcutaneous injection. Although flu-like symptoms and mild somnolence were commonly experienced side-effects; cessation of IFN treatment as a result of such effects was necessary in only three patients. All patients irrespective of previous treatment showed some response and a complete (less than 5% hairy cells, HCs) bone marrow response was observed in 17. The degree of response was related to the duration of therapy. Immunological markers showed that there was no apparent increase in natural killer (NK) cells and no return of normal B lymphocytes. Light-chain-restricted B cells became reduced in parallel with the disappearance of morphological HCs. Absolute numbers of T cells were reduced, Leu2a+ preferentially, resulting in an increase in helper/suppressor ratios. The ratios (saturation index, SI) of saturated to unsaturated 18 carbon fatty acids (C18FA) of erythrocyte or leukocyte membranes, while abnormal in untreated patients, approached normal levels during IFN therapy. It is concluded that prolonged alpha IFN therapy is highly effective in HCL. The mechanism of action of IFN remains unknown, but indirect surface-marker data favours a direct effect on HCs.

Adult

Reduction in the stearic to oleic acid ratio in human malignant liver neoplasms.

Total lipid extracts of liver tissue from 14 patients with primary and secondary liver tumours were analysed for relative values of saturation of 18 carbon chain length fatty acids (C18FA). The saturation indices (ratio C18S:C18u) of the tumour areas were significantly and consistently lower than the corresponding values in the non-tumour areas (P less than 0.001). It is proposed that the relative increase in unsaturated C18FA (oleic acid) could prove to be a chemical marker reflecting deficient cellular control of the desaturation of stearic acid.

Adult