Once daily dosing of aminoglycosides.
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Biomedical subjects
Publications and source records attributed to D Barnes.
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The serum-free mouse embryo (SFME) cell line, derived in serum-free medium from 16-day-old mouse embryos, exhibits unique properties. SFME cells grow indefinitely in culture without senescence, require epidermal growth factor (EGF) or fibroblast growth factor (FGF) for survival and are growth-inhibited by serum. The cell line expresses glial fibrillary acidic protein (GFAP) in response to transforming growth factor beta or serum and cells with similar properties can be isolated directly from brain. Culture of SFME cells with leukemia inhibitory factor (LIF), a peptide implicated in neural tissue development, also resulted in expression of GFAP. Other peptides that share signal transduction mechanisms with LIF--ciliary neurotropic factor, oncostatin M and interleukin-6--also caused expression of GFAP in these cells. These effects were inhibited by concentrations of EGF or FGF that promoted rapid cell growth.
The serum-free mouse embryo (SFME) cell line was isolated from 16-day-old Balb/c mouse embryos in medium in which the usual serum supplement to the culture medium was replaced by purified growth factors and other components. SFME is an unusual line that does not undergo senescence in vitro, maintains an apparently normal karyotype, and is growth inhibited by serum. Transforming growth factor beta (TGF beta) or calf serum induces expression of the astrocyte marker glial fibrillary acidic protein (GFAP) in these cells, and similar cells can be isolated directly from brain. By differential screening of a cDNA library derived from SFME cells, a calf serum- and TGF beta-regulated 8.5 kb mRNA was identified in SFME cells and the cDNA partially sequenced. This mRNA was detected only in RNA preparations from brain among a number of tissues examined, and may provide an additional marker of TGF beta-regulated differentiation in these cells.
Mammalian cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) form a supergene family consisting of four distinct families, named alpha, mu, pi and theta. In humans one member of the mu class gene family (GSTM1) has been shown to be polymorphic and is only expressed in 55-60% of individuals. Previous studies have shown a possible link with the null phenotype and susceptibility to cancer, in particular to lung cancer. In this study we genotyped individuals with breast, bladder and colorectal cancer. A total of 490 individuals with cancer were studied, and consisted of 97 bladder, 197 breast and 196 colorectal cancers. No significant differences were observed in the frequency of nulled individuals in bladder or breast cancer patients when compared with a control population of 225 individuals. However, a significant excess of nulled individuals were seen in colorectal cancer: 56.1% compared with the control group value of 41.8%. This was shown to be highly significant depending on the site of the tumours and > 70% of individuals with a tumour in the proximal colon were GSTM1 nulled. This is an approximately 2-fold increase in colon cancer risk in these individuals.
This paper presents a characterization of the fluorescence properties of human eosinophils isolated from peripheral blood of normal donors over a wide range of excitation and emission wavelengths. Circulating eosinophils possess three fluorescence excitation emission maxima: one at 280 nm excitation, 330 nm emission, attributable to tryptophan fluorescence, and currently unassigned peaks at 360 nm excitation, 440 nm emission and 380 nm excitation, 415 nm emission. Fluorescence microscopy studies show that the fluorescence of eosinophils may be site dependent; specifically, when observed at 365 nm excitation, circulating eosinophil fluorescence appears blue-violet, while the fluorescence of tissue-dwelling eosinophils appears amber-gold. These results should be considered in developing an optical biopsy technique to identify eosinophils in human tissue.
Seventy four patients with clinically definite multiple sclerosis were studied by using polyacrylamide gel electrophoresis of cerebrospinal fluid to assess blood-brain barrier function. Blood-brain barrier impairment was associated with recent clinical relapses of multiple sclerosis and worsened across a spectrum from the relapsing-remitting type of multiple sclerosis to secondary and primary progressive disease. The association between blood-brain barrier impairment and primary progressive disease is particularly interesting in the light of recent evidence that focal gadolinium enhancement on MRI is relatively unusual in patients with this disease.
Two experiments explored the effects of two types of concurrent activity on human fixed-interval performance. Eight adult subjects were given access to either reading material or a working television set across three fixed-interval values (60 s, 300 s, and 600 s). During Experiment 1, 2 subjects produced "scalloped" patterns and reported no verbal regulation (e.g., counting) in the presence of the reading material, but shifted to low-rate patterns and reported verbal regulation when the reading material was withdrawn. The 2 other subjects in Experiment 1 produced consistent low-rate performances and reported verbal regulation during access to reading material. However, when these subjects were given access to a working television set, they produced scalloped patterns and reported no verbal regulation. During Experiment 2, 4 experimentally naive subjects showed consistent scalloped patterning and no verbal regulation across fixed-interval values when they were allowed to watch television. When access to the television was denied, subjects reliably reported verbal regulation, and low-rate patterns emerged. These behavioral effects focus our attention on the contingencies that control human performance on fixed-interval schedules.
During Experiments 1 and 2, subjects were trained in a series of related conditional discriminations in a matching-to-sample format (A1-B1, A1-C1 and A2-B2, A2-C2). A low-rate performance was then explicitly trained in the presence of B1, and a high-rate performance was explicitly trained in the presence of B2. The two types of schedule performance transferred to the C stimuli for all subjects in both experiments, in the absence of explicit reinforcement through equivalence (i.e., C1 = low rate and C2 = high rate). In Experiment 2, it was also shown that these discriminative functions transferred from the C1-C2 stimuli to two novel stimuli that were physically similar to the C stimuli (SC1 and SC2, respectively). For both these experiments, subjects demonstrated the predicted equivalence responding during matching-to-sample equivalence tests. In Experiments 3 and 4, the conditional discrimination training from the first two experiments was modified in that two further conditional discrimination tasks were trained (C1-D1 and C2-D2). However, for these tasks the D stimuli served only as positive comparisons, and ND1 and ND2 stimuli served as negative comparisons (i.e., C1 x ND1 and C2 x ND2). Subsequent to training, the negatively related stimuli (ND1 and ND2) did not become discriminative for the schedule performances explicitly trained in the presence of B1 and B2, respectively. Instead, the ND1 stimulus became discriminative for the schedule performance trained in the presence of B2, and ND2 became discriminative for the schedule performance trained in the presence of B1. All subjects from Experiment 4 showed that the novel stimulus SND1, which was physically similar to ND1, became discriminative for the same response pattern as that controlled by ND1. Similarly, SND2, which was physically similar to ND2, became discriminative for the same response pattern as that controlled by ND2. Subjects from both Experiments 3 and 4 also produced equivalence responding on matching-to-sample equivalence tests that corresponded perfectly to the derived performances shown on the transfer of discriminative control tests.
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The Braden Scale for Predicting Pressure Sore Risk was designed to predict patients at risk of forming pressure sores and has been tested in a variety of settings. In two studies with a cumulative n of 199, the sensitivity was 100% using 16 as a cut-off and the specificity ranged from 64% to 90%. In this study of 361 patients in a large, tertiary, acute-care facility, the Braden Scale sensitivity was 73% and specificity was 91%. Using 16 as the cut-off point, this instrument would have over-predicted pressure sore formation, but, more importantly, inadequate preventative measures would have been provided for 27% of the patient population.
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In an attempt to obtain cell lines from the different components found in primary breast cancers, we used a low-calcium medium to culture epithelial cells of mixed phenotype and a recombinant T antigen containing retrovirus to immortalize cells found in these cultures. In each case, the histology of the sample used for culture was examined in detail and the best growth was obtained from samples associated with a substantial in situ or benign component and from lobular rather than ductal carcinomas. Clonal cell lines were developed from each of 4 tumours: 1 infiltrating ductal (tumour number 2), 2 infiltrating lobular (tumours 3 and 5) and 1 mucoid (tumour 6). To try to identify the phenotype and origin of the cell lines, immunohistochemical markers, histological analysis of tissue sections and behavioural markers were used. All the cell lines expressed mainly luminal epithelial cell markers, but the basal epithelial keratin, keratin 14, was also expressed homogeneously or heterogeneously. Growth in agar was seen with some but not all cell lines derived from only 1 tumour (tumour 5) and tumour development in nude mice was observed (with low efficiency) with cell lines from only 1 tumour (tumour 6). The data suggest that the cell lines obtained from the infiltrating ductal carcinoma (tumour 2) developed from cells cultured from the associated benign component, while the cell lines from tumours 3, 5 and 6 may each have developed from a cell in an early stage of malignancy. When tested for their ability to undergo morphogenesis on extracellular matrix components, cell lines from tumour 2 made well-developed ductal-alveolar-like structures, while those from the other tumours did not.
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Receiver operating characteristic (ROC) analysis demonstrated that regional variations of sensitivity exist in the detection of wall motion abnormality in cardiac blood pool imaging studies. The observer response is significantly better in the apex than either the septum or posterolateral wall segments. The observer errors tend to be false-negative in the posterolateral wall segment and false-positive in the other two segments. Image presentation can make a significant difference to the overall sensitivity, and the monochrome cine-sequence performed best in this study.
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The new technique of nuclear magnetic resonance imaging (NMR) has been found to have particular value in the study of the evolution of the plaque of multiple sclerosis. Particularly when combined with gadolinium enhancement, the method not only shows very dramatically the waxing and waning of the plaque with time, it also demonstrates with remarkable clarity the important role of changes in vascular permeability in the pathological process. In this Annotation the ability of this technique to throw new light on the process of plaque formation and evaluation is critically assessed. In addition, the role of changing fluid content of the extracellular spaces of the CNS in influencing interpretation of the more conventional clinical and electrophysiological findings is discussed. While the method of NMR analysis does not yet show us how the plaque is initiated, it is suggested that future studies with these new techniques in the living subject may well lead us to rational therapeutic approaches based on pathogenetic mechanisms.