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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1995

Ion selectivity of the channels formed by pardaxin, an ionophore, in bilayer membranes.

Using the method of bilayer membranes at the tip of a patch pipette, the properties of the ionic channels produced by the ionophore toxin pardaxin were investigated. At low toxin concentrations, voltage-dependent, single-channel events were measured. The current-voltage curves were non-linear when determined in Tris-Cl solution, but were linear in K(+)-HEPES solution. Using asymmetric ion solutions, the ionic selectivity of pardaxin channels was estimated from the reversal potentials obtained. The sequence of the relative permeabilities for monovalent cations was Tl+ > Rb+ > Cs+ > K+,NH4+ > methylamine+ > Li+ > dimethylamine+ > Na+. Except for Li+, the selectivity sequence fitted the cations relative hydrated size. For bivalent ions the permeability of Ba2+, Sr2+, and Mn2+ relative to Mg2+ changed according to the relative hydrated size. For anions the selectivity sequence was I- > NO3- > Br- > Cl- > ClO4- > SCN- > BF- > HCOO- > F- > CH3COO-. The selectivity sequence for the small anions (I-, NO3-, Br-, Cl-) was different from their hydrated size. Pardaxin channel showed a modest ion selectivity between small anions and cations (PK:PCl:PNa = 1.28:1.00:0.56). Pardaxin is proposed as a biophysical model to study ionic channel selectivity.

Cell Membrane Permeability↗
PubMed1995

Chorioamnionitis caused by Capnocytophaga: case report.

Intraamniotic infection is a significant cause of perinatal morbidity. Capnocytophaga, a gram-negative anaerobe found in the oral cavity, has been implicated as an unusual cause of neonatal sepsis. We report a patient in whom this unusual organism was identified and describe the postpartum and neonatal courses.

Adult↗
PubMed1995

Lack of correlation of soluble E-selectin level with renal transplant rejection.

E-Selectin is a 115-kDa cell surface glycoprotein transiently expressed on vascular endothelium in response to interleukin-1 and tumour necrosis factor-alpha with a peak in expression at four hours. Its distribution in transplant biopsies has been associated with inflammatory events such as allograft rejection. Recently, a soluble isoform of E-selectin has been detected in the culture medium of cytokine activated endothelial cells by an ELISA method. In this study soluble E-selectin levels in renal allograft recipients were compared with the incidence of rejection, acute tubular necrosis (ATN), cyclosporin A (CyA) toxicity, and use of orthoclone OKT3 (muromonab-CD3) to establish whether early endothelial activation and inflammatory damage could be detected. The mean soluble E-selectin level in normal volunteers was 89 ng/ml serum compared to 120 ng/ml for a group of chronic renal failure patients. Soluble E-selectin levels declined upon transplantation but this was not significant, nor was the difference in samples from patients experiencing rejection, ATN or CyA toxicity. A dramatic and sustained rise in soluble E-selectin levels was found within 24 hours of the first dose of OKT3 treatment. This study shows that soluble E-selectin does not provide early unequivocal indication of pathological sequelae in renal transplantation, although extensive endothelial activation can be demonstrated with OKT3 treatment.

Biomarkers↗
PubMed1995

Monoclonal antibodies against human collagenase and stromelysin.

Mouse monoclonal antibodies against recombinant human fibroblast procollagenase and prostromelysin have been generated and characterized. The epitope-containing domains for the antibodies have been assigned based on their immunoreactivities against recombinant proenzymes, mature enzymes, truncated collagenases, proteolytic fragments of stromelysin, and chimeric molecules constructed from different domains of the two enzymes. These antibodies can be divided into four groups: (1) antibodies that recognize the truncated 19-kDa NH2-terminal collagenase, (2) antibodies that recognize the C-terminal domain of collagenase and stromelysin, (3) antibodies that recognize a 31-kDa NH2-terminal collagenase fragment, and (4) antibodies that recognize the 19-kDa NH2-fragment of stromelysin. The prostromelysin-specific antibody 11N13 is of particular interest; it neutralizes stromelysin activity in a stromelysin peptide substrate assay, with an IC50 value of 75 nM. MAb 11N13 may be useful for in vivo and in vitro studies to validate the roles of stromelysin in tumor cell invasion, metastasis, and connective tissue disorders.

Amino Acid Sequence↗
PubMed1995

The effects of glucosinolates and their hydrolysis products on microbial growth.

Rapemeal, which contains potentially toxic compounds such as glucosinolates, was assessed as a substrate for the growth of micro-organisms. The effects of glucosinolates and their degradation products were tested on a range of industrially important microbial species. Sinigrin (2-propenyl glucosinolate) was found to be relatively innocuous to all of the organisms tested but its hydrolysis to yield isothiocyanates, thiocyanates and nitriles resulted in inhibition of growth. The initial inhibitory sinigrin concentration before its hydrolysis was found to be species-dependent with Bacillus subtilis being the most resistant (80 micrograms ml-1) and Saccharomyces cerevisiae (40 micrograms ml-1) the most sensitive. Three Gram-positive organisms tested were found to be more resistant to hydrolysis products than other micro-organisms. Similar results were observed with phenylisothiocyanate for which inhibition was found to be inhibitor and cell concentration-dependent. Addition of thioglucoside glucohydrolase during active growth of Escherichia coli in a sinigrin-containing liquid medium reduced the number of viable cells. Similar effects were also observed in rapemeal media in which growth inhibition was dependent on the glucosinolate content of the rapemeal.

Bacillus↗
PubMed1995

Rapid assessment of physiological status in Escherichia coli using fluorescent probes.

Rapid and direct viability assessment of Escherichia coli in filtered, sterile lake water was possible using multiparameter flow cytometry. Fluorescent dyes were used as probes for different cellular functions (membrane potential, membrane integrity and intracellular enzyme activity), which were correlated with the ability of the cells to respond to nutrient addition while in a stressed state. Measurement of several criteria circumvented limitations imposed by other methods, and provided extensive evidence for the validity of the methods for monitoring cell viability during adoption of a viable-but-non-culturable state in starved E. coli. Macromolecular staining was concomitantly used to monitor changes in cellular protein, RNA and DNA as additional indicators of physiological status during starvation/stress.

Escherichia coli↗
PubMed1995

The effects of protective occlusive gloves on stratum corneum barrier properties.

Data suggests that protection from gloves is paradoxically reduced because of effects of occlusion on the skin. The aim of this study was to characterize these effects on physical and functional properties of stratum corneum. Volunteer trials were conducted using patches of polyvinyl chloride (PVC) glove material on the skin. Impairment of barrier function was assessed by measuring transepidermal water loss (TEWL). Hydration and water sorption-desorption was assessed using skin conductance. The major finding was a short-term impairment of barrier function, measured as an increase in TEWL of 1.7 gn-2h-1 (95% C.I. 0.4 to 2.6 gn-2h-1,p < 0.01). Temporary increases in hydration and water sorption were also observed. On this basis, the effects of wearing PVC gloves over 2 days on stratum corneum barrier properties on the dorsum of the hand were studied. TEWL measurements remained elevated by 1.5 gn-2h-1 the day after occlusive glove removal (95% C.I. 0.2 to 2.8 gn-2h-1, p < 0.01), indicating a possible cumulative effect. In conclusion, our studies demonstrate a potential hazard resulting from the repeated use of protective gloves.

Adult↗
PubMed1995

OV 632 and MOC 31 in the diagnosis of mesothelioma and adenocarcinoma: an assessment of their use in formalin fixed and paraffin wax embedded material.

AIMS: To investigate the reaction of antibodies OV 632 and MOC 31 in paraffin wax sections as opposed to frozen sections and cytological preparations; to evaluate their usefulness in the differential diagnosis of malignant mesothelioma and secondary adenocarcinoma of the pleura; and to assess the efficacy of microwave pretreatment of sections in unmasking their associated epitopes. METHODS: Immunohistochemistry, using a standard avidin-biotin technique, with microwave pretreatment and trypsinisation in a certain proportion of cases. The material comprised 43 mesotheliomas, 44 adenocarcinomas and five reactive pleuras. RESULTS: Epithelial mesotheliomas and the hyperplastic mesothelial cells reacted strongly with OV 632, the reaction with sarcomatoid and desmoplastic tumours was weak, and the reaction with adenocarcinomas was variable. An unequivocal but sometimes patchy positive reaction was obtained with MOC 31 in all but one of the adenocarcinomas; all but one of the mesotheliomas and all the reactive pleuras were negative. Review of the two apparently anomalous cases revealed that the original diagnoses had probably been incorrect. Reactions to both antibodies were abolished by microwave pretreatment, and also by prior trypsinisation in the case of OV 632. CONCLUSIONS: OV 632 is unsuitable for routine clinical use in paraffin wax embedded material. MOC 31, however, would be a useful addition to a panel of antibodies in the differential diagnosis of mesothelioma and adenocarcinoma in large biopsy and resection specimens and necropsy material. Its value in small biopsy specimens remains to be assessed. Microwave pretreatment does not enhance the reactions with either antibody.

Adenocarcinoma↗
PubMed1995

Carboplatin reinduction after taxane in patients with platinum-refractory epithelial ovarian cancer.

PURPOSE: To determine the activity of carboplatin in patients with ovarian cancer who progressed on taxane (paclitaxel or docetaxel) therapy. PATIENTS AND METHODS: Thirty-three patients with ovarian cancers refractory to platinum and taxane therapy were treated with single-agent carboplatin reinduction once the disease progressed on a taxane. The starting dose of carboplatin was 300 mg/m2 at 28-day intervals. RESULTS: Patients were a median age of 56 years (range, 31 to 80), had a median Zubrod performance status of 1 (range, 0 to 2) and had received a median of three prior chemotherapy regimens (range, two to eight) and one pretaxane platinum regimen (range, one to three). Twenty-six patients had a platinum-free interval of at least 12 months at the time of posttaxane re-treatment with carboplatin. There were seven of 33 (21%) partial responses, with a median duration of 7+ months (range, 2+ to 12+). Responses were noted only in patients with at least a 12-month platinum-free interval and an initial sensitivity to a taxane. The therapy was well tolerated and neurotoxicity was absent. CONCLUSION: A subset of patients with platinum-refractory disease that initially responded to a taxane and who eventually have a platinum-free interval of at least 1 year may respond to carboplatin reinduction. This finding may be secondary to paclitaxel or docetaxel therapy that leads to the reversal of platinum resistance, or the prolonged platinum-free interval permits the loss of resistance to platinum by the tumor. Carboplatin reinduction should be considered in the treatment of patients whose ovarian cancer progresses after an initial sensitivity to a taxane and who had a prolonged platinum-free interval.

Adult↗
PubMed1995

The influence of age, liver size and enantiomer concentrations on warfarin requirements.

1. We have tested the hypothesis that the fall in hepatic mass with age influences the age related increase in sensitivity to warfarin. In 39 otherwise healthy outpatients, aged 50-87 years, stabilised on warfarin for prophylaxis of thromboembolism, age, mean International Normalised Ratio (INR), and mean warfarin dosage were recorded. Liver volume was measured by ultrasound, and plasma was assayed for trough concentrations of (R)- and (S)-warfarin. 2. There was a negative correlation between age and liver volume (r = -0.41; P = 0.01) and age and dose (r = -0.53; P = < 0.001) and a positive correlation between liver volume and dose (r = 0.49; P = 0.002). There was no significant correlation between dosage and (R)- and (S)-warfarin concentrations, nor between dosage and INR. 3. The regression model including both age and liver volume data showed a better fit for estimation of warfarin dosage requirement than regression models based on age and liver volume data alone. Ninety-five per cent prediction intervals for warfarin dose requirements were wide, whether age alone, or age and liver volume were used in calculations. 4. Due to inter-individual variation in warfarin dosage requirements related to other influences, both explained and unexplained, routine measurement of age and liver volume would not contribute further clinically useful information to that obtained by the INR test currently used for predicting warfarin dosage requirements.

Age Distribution↗
PubMed1994

Isolation of glucosinolate degrading microorganisms and their potential for reducing the glucosinolate content of rapemeal.

A range of microorganisms were assessed for their ability to degrade glucosinolates, using sinigrin (2-propenyl glucosinolate) as a model compound. Eight different species capable of growing on sinigrin as a sole carbon source were isolated. These were predominantly Gram-positive bacteria which also degraded the natural glucosinolates within rapemeal. Growth of the majority of these organisms in a sinigrin/glucose liquid medium wass biphasic; glucose was utilised during the initial rapid phase of growth. The ability to degrade sinigrin was found to be unstable and was rapidly and irreversibly lost when organisms were cultured on sinigrin-free media.

Animal Feed↗
PubMed1994

Extraction and high-performance liquid chromatographic method for the determination of microcystins in raw and treated waters.

Increasing concern over the presence of microcystins (cyanobacterial/blue-green algal hepatotoxins) in water supplies has emphasized the need for a suitable analytical method. As many microcystins are known to exist, a method was developed that permits the determination of numerous variants by a single procedure. The method involves filtration to separate cyanobacterial cells from water, allowing intracellular and extracellular toxin levels to be assessed. The cellular components of the samples are extracted repeatedly in methanol, which was found to be the most versatile solvent tested for the extraction of microcystins. The efficiency of this extraction procedure was found to be independent of cell biomass. The filtered water was subjected to trace enrichment using a C18 solid-phase extraction cartridge, followed by identification and determination by photodiode-array high-performance liquid chromatography. The procedure was assessed using four water samples (two raw and two treated) spiked with a mixture of five microcystins and the cyanobacterial hepatotoxin nodularin. Recoveries of all but one microcystin were found to be good when spiked with concentrations as low as 250 ng l-1. The linearity and precision of the experimental procedure were assessed for five microcystins and nodularin. The proposed method permits rapid sample processing and determination of several microcystins.

Chromatography, High Pressure Liquid↗
PubMed1994

Effects of health facilitator performance and attendance at training sessions on the acquisition of tobacco refusal skills among multi-ethnic, high-risk adolescents.

The study examined the effectiveness of a psycho-social tobacco use prevention intervention with a refusal skills training component on the refusal skills of high-risk adolescents, and investigated skill acquisition as related to subject demographics, performance of health facilitators and attendance at skills training sessions. Tobacco refusal skills were assessed for a group (n = 389) of high-risk, seventh-grade students participating as intervention and control subjects in Project SHOUT, a large tobacco use prevention program in the San Diego area. In addition, subject demographics, ratings of health facilitator performance and information about subjects' attendance at skills training sessions were collected. Subjects' responses to audiotaped peer offers of cigarettes and smokeless tobacco were coded for content and quality. Greater tobacco refusal skills among intervention subjects was hypothesized. Further health facilitator performance, attendance at training sessions and subject demographics were thought to be related to skill acquisition. High-risk intervention subjects gave significantly higher quality tobacco-refusal responses than did controls, although the differences between means were small. Results suggested that Hispanic adolescents were particularly receptive to the refusal skills training. The association between health facilitator performance and skill acquisition varied by subject ethnicity, as did the relationship between attendance at training sessions and skill acquisition.

Adolescent↗