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Biomedical subjects

W Barker

Publications and source records attributed to W Barker.

At least 55 records · Page 3Linked to original sources

Increased erythrocyte stearic acid desaturation in rats with chemically induced colorectal carcinomas.

Our previous studies have demonstrated a desaturation of stearic acid related to oleic acid in the lipid layer of erythrocytes in patients with malignancies. This study investigated the stearic acid desaturation in red blood cell membranes of rats during the induction of colorectal tumours. Male Sprague-Dawley rats were injected weekly with dimethylhydrazine (DMH) and sacrificed at 4-week intervals. Blood was withdrawn via heart puncture, collected in EDTA bottle and erythrocytes separated by centrifugation. Total lipid extraction was carried out and analysed with gas liquid chromatography. In the control rats (injected with normal saline) the mean of the stearic to oleic acid ratio in erythrocyte membranes was 2.0 +/- 0.3 (n = 28, range 1.51-2.62) compared to a mean of 0.94 +/- 0.16 (n = 0.5-1.23) in tumour bearing rats (p less than 0.001). The increased desaturation occurred in parallel with appearance of tumours. These data suggest the regulation of stearic acid desaturation is an important adaptive mechanism of membrane fluidity and could be a useful chemical marker for malignancy.

Animals↗

Stearic acid and carcinogenesis.

Decreased membrane rigidity is one of the characteristics of malignant cells, resulting in part from the desaturation of stearic acid into oleic acid. In this study we investigated the influence of stearic acid on tumour cell inhibition in vitro and tumour development in vivo. Stearic acid inhibited the colony-forming ability of 4 out of 5 rat and two human tumour continuous cell lines in vitro. In contrast, the colony-forming ability of rat fibroblasts was not inhibited and that of human foetal lung fibroblasts was inhibited at a higher dose than that required to inhibit human tumour cell lines. Using a model of rat mammary carcinoma induced by nitroso-methyl urea (NMU) the subcutaneous injection of stearic acid at weekly intervals prevented tumour development in 5 to 10 rats. Using iodostearic acid twice weekly, 11 of 19 rats were alive and tumour free at week 22 whilst all of 14 animals injected with NMU alone had died of tumour by the 16th week. The ratio of stearic to oleic acids in erythrocyte membranes was significantly reduced in the tumour-bearing rats, but was normal in tumour-free animals treated with stearic or iodostearic acid. These preliminary data indicate that stearic acid inhibits tumour development in rats.

Animals↗

Two behavioral states studied in a single PET/FDG procedure: theory, method, and preliminary results.

We have developed a method that allows two sets of regional cerebral metabolic rates of glucose (rCMRglc) to be obtained in a single extended procedure using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). This is an adaptation of the deoxyglucose method, with the addition of a second injection of FDG immediately after completion of the first scan, then followed 30 min later by a second scan. A model has been developed to allow for correction of measured tracer concentration in the second scan by subtracting the predicted remnant from the first scan. The possible applications of this method in studying behavior-metabolism relationships are demonstrated. The preliminary results show 6%-12% changes in rCMRglc values for appropriate brain regions when the behavioral state is altered, but show 0%-5% change in rCMRglc values when the behavioral state is unchanged. The method can contribute significantly to the understanding of behavior-metabolism relationships by allowing the noninvasive study of two behavioral states in a single PET procedure.

Brain↗

Desaturation-producing factor present in the tissue, blood, and urine of cancer patients.

Patients with liver neoplasms have a significantly lower stearic to oleic ratio (SI) in tumour (x = 0.36) vs non-tumour liver tissues (x = 0.75; P less than 0.001). The SI of circulating erythrocytes is lower in cancer patients (n = 100; X = 0.69) than noncancer patients (n = 50; x = 1.45) and normal subjects (n = 50; x = 1.5) (p less than 0.001). It was also found that urine protein extracts from cancer patients reduce the SI of cultured cell membrane (n = 10; x = 0.74) as compared to urine from noncancer patients (n = 10; x = 1.02; p less than 0.001). This study suggests that patients with cancer release a desaturation-producing factor from the malignant cells into the systemic circulation and subsequently into the urine. The observed increased unsaturation (oleic acid) in the circulating erythrocytes can be useful in the diagnosis and postoperative monitoring of cancer patients.

Adult↗

Inter- and intra-examiner reliability of the upper cervical X-ray marking system: a second look.

To determine the degree of reliability (stability over time) for six Pettibon practitioners, the scores resulting from the reading and re-reading of 30 X rays were analyzed using bivariate scattergrams, Pearson Product-moment correlation coefficient estimates and correlated samples t tests. To examine reliability (equivalence over experts) across the practitioners, a repeated measures analysis of variance approach was used. Liberal and conservative reliability coefficients for the upper angle and lower angle were computed. Examination of the data suggest that the reliability (stability over time) for the practitioners is very good. The data on reliability (equivalence over experts) across the practitioners also suggests reliability is very good.

Cervical Vertebrae↗

Increase of oleic acid in erythrocytes associated with malignancies.

Total lipid extracts of erythrocyte cell membranes from 60 patients with documented malignancies, 41 patients with various acute and chronic diseases, and 40 healthy subjects were analysed. The results were expressed as ratios of stearic to oleic acid, reflecting the degree of desaturation of stearic acid. The mean ratios for the healthy subjects and controls without cancer were 1.5 (SD 0.27) and 1.45 (0.28), respectively, whereas the ratios for patients with malignancies were consistently lower than the cut off point of 1.0, with a mean of 0.69 (0.15) (p less than 0.001). The desaturation ratio was also significantly lower (p less than 0.001) in the group with recurrent tumours (mean 0.75 (0.04)) compared with those with no evidence of recurrent tumours (mean 1.55 (0.27)). It is suggested that the increased unsaturation (oleic acid) in the circulating erythrocytes may be useful in the diagnosis and postoperative monitoring of patients with cancer.

Erythrocyte Membrane↗

Reduction in the stearic to oleic acid ratio in leukaemic cells--a possible chemical marker of malignancy.

Total lipid extracts of peripheral blood cells from patients with chronic leukaemias were analysed for relative values of saturation of the eighteen carbon chain length fatty acids (C 18 FA). The results are expressed as saturation index (C 18 S:C 18 U) of the saturated C 18 FA (stearic acid) over the unsaturated C 18 FA (oleic, linoleic and linolenic acids). The saturation indices of the white blood cells (WBC) and the red blood cells (RBC) in specimens from 14 patients with chronic granulocytic leukaemia (CGL) and 17 patients with chronic lymphocytic leukaemias (CLL) were significantly and consistently lower than control specimens. It is proposed that the relative increase in the unsaturated oleic acid could prove to be a chemical marker of malignancy reflecting a deficient cellular control of the process of stearic acid desaturation. The theoretical implications of the implied increase in membrane fluidity for the cells are discussed.

Chromatography, Gas↗

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↗

Reduction in the stearic to oleic acid ratio in the circulating red blood cells: a possible tumour marker in solid human neoplasms.

Gas liquid chromatography study of the 18 carbon chain length fatty acids (C18FA) of the human red blood cells (RBCs) was performed on 65 patients with various clinical disorders. It was found that the stearic to oleic acid ratio (SI) of the RBCs was significantly lower (P less than 0.001) in patients with malignant conditions (n = 20, SI = 0.62 +/- 0.16) compared with pathological non-malignant diseases (n = 10, SI = 1.19 +/- 0.2) and the normal control group (n = 35, SI = 1.57 +/- 0.5). Our early results suggest that the increased unsaturation (oleic acid) in the circulating RBCs could be used as a chemical marker in various solid neoplasms.

Chromatography, Gas↗

Damage to tissue defenses by a topical anesthetic agent.

The purpose of this study was to determine the effect of a topical application of a solution containing 0.5% tetracaine, 1:2,000 epinephrine, and 11.9% cocaine on the wound's ability to resist infection. In this experimental study, this solution potentiated the development of wound infection. This effect can be explained by its vasoconstrictive action limiting access of the cellular defenses to the bacteria on the wound surface.

Administration, Topical↗

Reversible increase in the saturation of C18 fatty acids induced by diphtheria toxin in tissue culture cells.

Diptheria toxin (DT) reversibly increases the saturation of the long-chain C18 fatty acids (C18FA) in concentrations which are at least 100-fold smaller than the concentrations which completely inhibit host cell protein synthesis. The concentrations required for induction of the increase in the saturation of the C18FA in fibroblasts are 100-fold smaller than the concentrations for the epithelial cells. The increase in saturation of the C18FA was proportional to the concentration of DT. A cytopathic effect appeared with DT concentrations which induced a near-maximal increase in the saturation of the C18FA, but the cells remained viable. However, at very high concentrations of DT and depending on the type of cell, there was no change in the fatty acids, and the treated cells disintegrated. Interferon, which also induces a reversible increase in the saturation of the C18FA (K. Apostolov and W. Barker, FEBS Lett. 126:261-264, 1981), produces a cumulative effect when used in conjunction with DT. This additive effect of DT and interferon is discussed in the light of other similar biological activities of these agents.

Animals↗