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Biomedical subjects

D Barnes

Publications and source records attributed to D Barnes.

At least 199 records · Page 11Linked to original sources

A comparative study of the cytotoxicity and DNA-damaging effects of cis-(diammino)(1,1-cyclobutanedicarboxylato)-platinum(II) and cis-diamminedichloroplatinum(II) on L1210 cells.

Utilizing the DNA alkaline elution technique we have compared qualitatively and quantitatively the DNA lesions produced in L1210 cells after a 2 h exposure to the antitumor agents, cis-(diammino) (1,1-cyclobutanedicarboxylato)-platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (DDP). DNA-protein and DNA interstrand cross-links are formed in cells exposed to either CBDCA or DDP. However, in comparison to DDP peak levels of these lesions occur 6 to 12 h later in CBDCA treated cells. Cytotoxicity studies reveal that CBDCA is 45 times less potent than DDP to L1210 cells when compared on a molar basis. The decreased cytotoxicity of CBDCA and the 12 h delay in peak cross-linking when compared to DDP is interpreted as a decreased reactivity of the intact CBDCA towards the DNA. This decreased reactivity may be due in part to the presence of a stable bidentate dicarboxylate chelate ring structure of CBDCA resulting in a much slower rate of hydrolysis to the active form of the drug.

Animals↗

The effect of illness behaviour on the apparent relationship between physical and mental disorders.

Evidence for associations between organic disease and psychopathology is reviewed and it is concluded that some of this is determined by complaint and consultation behaviours. The concept of illness behaviour is described. The Self Care Assessment Schedule (SCAS) is a new measure of illness behaviour and has been used to provide an independent assessment of psychiatric day patients, gynaecology and surgical outpatients. Only weak positive correlations were found between SCAS scores and mental illness, measured using the General Health Questionnaire (GHQ). Subjects with organic pathology differed little from those without organic pathology, with regard to SCAS and GHQ scores. However SCAS and GHQ scores were more highly correlated in those without organic pathology. It is concluded that claimed associations between physical disease and psychopathology should be based on objective evidence rather than subjective complaints and that this should be found across the entire spectrum of illness behaviour.

Ambulatory Care↗

Angiotensin II rapidly increases phosphatidate-phosphoinositide synthesis and phosphoinositide hydrolysis and mobilizes intracellular calcium in cultured arterial muscle cells.

Smooth muscle cells were cultured from rat thoracic aorta and labeled to a stable specific activity with 45Ca2+, myo-[2-3H]inositol, or 32Pi. The efflux of 45Ca2+ was monitored over 10-sec intervals. Angiotensin II (AII) increased the amount of 45Ca2+ lost by 5-fold in the first 10-sec interval after the addition of AII and by 10-fold in the second 10-sec interval. AII-stimulated 45Ca2+ release was blocked by the angiotensin antagonist [1-sarcosine, 8-leucine]AII and by La3+. The removal of external Ca2+ had no effect on AII-stimulated 45Ca2+ release. Depolarization with high external K+ only slightly increased 45Ca2+ efflux and had no effect on AII-induced 45Ca2+ release. AII had no effect on the initial rate of 45Ca2+ influx. These results indicate that the rapid 45Ca2+ efflux evoked by AII is probably due to the release of 45Ca2+ sequestered intracellularly rather than to an increase in the Ca2+ permeability of the plasma membrane. AII provoked rapid increases in the levels of phosphatidic acid and phosphoinositides in the cells. These increases in phospholipids were associated with increases in phospholipase C-generated inositol phosphates (tri-, di-, and mono-). It appears that AII simultaneously increases phosphoinositide hydrolysis and synthesis in vascular smooth muscle, and both phospholipid effects may contribute to inositol triphosphate generation, which was sufficiently rapid to have a role in intracellular Ca2+ mobilization.

Angiotensin II↗

The mechanism of action of insulin on phospholipid metabolism in rat adipose tissue. Requirement for protein synthesis and a carbohydrate source, and relationship to activation of pyruvate dehydrogenase.

We studied certain metabolic requirements for insulin-induced increases in phospholipids, and the relationship of phospholipid changes to the insulin-induced activation of pyruvate dehydrogenase, in rat adipocytes and fat pads in vitro. Increases in the contents of phosphatidylinositol and phosphatidylserine mass were maximal in rat fat pads within 10 min of incubation with insulin, and preceded or accompanied measurable increases in pyruvate dehydrogenase activity. In dose-response studies, the contents of these phospholipids and pyruvate dehydrogenase activity increased in parallel in response to increasing concentrations of insulin. Cycloheximide and puromycin inhibited insulin-induced increases in the mass of both of these phospholipids, as well as (in confirmation of previous reports) pyruvate dehydrogenase activity. Effects of insulin on phospholipid metabolism and pyruvate dehydrogenase were found to require an exogenous carbohydrate source, and fructose was nearly as effective as glucose in this regard. Insulin-induced increases in phosphatidylinositol and phosphatidylserine were demonstrated in the mitochondrial fraction, which is also the subcellular locus of pyruvate dehydrogenase. The present findings suggest that there is a relationship between insulin-induced increases in phospholipids and pyruvate dehydrogenase activity, but the nature of this relationship remains to be defined.

Adipose Tissue↗

Cell attachment on replicas of SDS polyacrylamide gels reveals two adhesive plasma proteins.

A novel procedure that detects adhesive proteins in complex mixtures was used to characterize such proteins in plasma. The proteins are separated by SDS PAGE and transferred to nitrocellulose filters. Cells incubated on these filters attach to those proteins that have adhesive properties. When applied to human plasma proteins this procedure reveals, in addition to fibronectin, a cell-attachment protein with a polypeptide molecular weight of 70,000. Using a monoclonal antibody that inhibits attachment of cells to fibronectin, we show that this polypeptide is not a fragment of fibronectin and we present evidence that it is a component of the serum spreading factor. Therefore, as defined by our assay, this protein and fibronectin are the major attachment proteins for fibroblastic cells in plasma or serum.

Animals↗

Human cells in serum-free medium.

Cell culture media in which the usual serum supplement required for growth has been replaced with specific combinations of hormones, nutrients and purified serum proteins have been developed which allow the growth of a number of human cell types. These media afford particular advantages in terms of simplicity of experimental design for some kinds of experiments. Also, the media may be designed to be selective with regard to cell type, so that fibroblastic overgrowth of primary cultures of epithelial cells can be avoided. Often the proliferative and differentiative responses of cells in vivo are better preserved in vitro in the serum-free media, resulting in new systems in which to study cell differentiation and responses of cells to environmental factors such as hormones.

Blood Proteins↗

Effects of a serum spreading factor on growth and morphology of cells in serum-free medium.

A heat-sensitive, trypsin-sensitive factor that promoted growth and spreading of cells in serum-free, hormone-supplemented medium was partially purified from human serum. The major portion of the proteins in these preparations migrated upon SDS-polyacrylamide gel electrophoresis with a mobility consistent with molecular weights between 60,000 and 90,000. The spreading activity, which we have termed serum spreading factor, stimulated growth and spreading of a wide variety of cell types. The serum spreading factor was similar to fibronectin in that it showed an affinity for the plastic cell culture substrate but was shown to be distinct from fibronectin by several criteria. This factor may prove useful in studies of cell attachment and spreading and in studies of the relationship of cell shape and cell proliferation.

Animals↗

Serum glycoprotein hormone alpha subunit, hormone receptors and disease stage in patients with breast cancer.

The concentration of the common alpha subunit of the glycoprotein hormones was high in the serum of 21/56 (38%) of premenopausal patients and 22/106 (21%) of postmenopausal patients with primary breast cancer, at the time of presentation. 7/59 (12%) of patients with benign disease also had high alpha subunit levels. Tumour cytosol oestrogen and progesterone receptor status was determined in 80% of the patients with cancer, and there was a trend towards higher alpha levels in patients without receptors, but this was not statistically significant. In the premenopausal patients with cancer there was a significant correlation between alpha subunit level and disease stage, R = 0.47, P = 0.0001, but not in the postmenopausal patients. In view of the correlation with disease stage, high levels of alpha subunit in premenopausal patients with breast cancer at presentation with the primary tumour may indicate poor prognosis.

Adult↗

Protracted radiation-stressed primate performance.

An experimental investigation has been made of the effects of nuclear radiation on the behavior of four trained primates (rhesus monkeys) proficient in control of the primate equilibrium platform during a hypothetical 72-h aircraft mission. The radiation exposure was assumed to result from a radioactive cloud penetration at the start of the mission, with subsequent low dose rate exposure resulting from radioactive debris in and on the aircraft. Minor performance changes were detected in three of four subjects; all experienced emesis.

Animals↗