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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 181 records · Page 10Linked to original sources

Oscillating activity of a calcium-activated K+ channel in normal and cancerous mammary cells in culture.

Calcium-activated potassium channels were the channels most frequently observed in primary cultured normal mammary cell and in the established mammary tumor cell, MMT060562. In both cells, single-channel and whole-cell clamp recordings sometimes showed slow oscillations of the Ca2(+)-gated K+ current. The characteristics of the Ca2(+)-activated K+ channels in normal and cancerous mammary cells were quite similar. The slope conductances changed from 8 to 70 pS depending on the mode of recording and the ionic composition in the patch electrode. The open probability of this channel increased between 0.1 to 1 microM of the intracellular Ca2+, but it was independent of the membrane potential. Charybdotoxin reduced the activity of the Ca2(+)-activated K+ channel and the oscillation of the membrane current, but apamin had no apparent effect. The application of tetraethylammonium (TEA) from outside and BaCl2 from inside of the cell diminished the activity of the channel. The properties of this channel were different from those of both the large conductance (BK or MAXI K) and small conductance (SK) type Ca2(+)-activated K+ channels.

Animals↗

Correlation of donor nutritional status with sinusoidal lining cell viability and liver function in the rat.

We have demonstrated that the sinusoidal lining cell injury sustained by rat liver allografts during hypothermic storage is a critical determinant of graft viability. The present study was designed to examine the effect of donor nutritional status on hepatic microcirculation and graft function. Rat livers from four nutritional groups (group I, fasted; group II, fed; group III, intraperitoneal glucose; and group IV, fed plus intraperitoneal glucose) were excised and stored for 24 hr in Marshall's isotonic citrate solution. Then the livers were perfused under anoxic conditions with trypan blue. The percentage of nonviable SLC in each group was 26.7 +/- 8.1, 24.9 +/- 7.9, 17.6 +/- 6.9, and 5.9 +/- 1.9 in groups I, II, III, and IV respectively; i.e., there was a significant improvement in SLC viability with nutritional repletion in group IV. Electron microscopy was performed on livers from groups I and IV following 30-hr preservation in University of Wisconsin solution and after 16-hr preservation in Marshall's isotonic citrate solution. Biopsies were taken at the end of storage and after 1 hr of reperfusion at 37 degrees C. At the end of preservation group IV livers contained glycogen and had much more normal liver ultrastructure than group I livers. After reperfusion there was partial recovery of normal SLC morphology in both groups and depletion of glycogen in group IV. Liver function was studied on the isolated perfused rat liver system at 37 degrees C following 30-hr storage in UW solution. Transaminase release into the perfusate was significantly lower in nutritionally repleted livers than in livers from fasted animals. A significant reduction in perfusate platelet count occurred only in livers from fasted animals. The results show that nutritional repletion can reduce the injury of cold preservation to both hepatocytes and endothelial cells and improve liver function in the postpreservation period.

Alanine Transaminase↗

The effects of temperature, pH and growth rate on secondary metabolism in Streptomyces thermoviolaceus grown in a chemostat.

Streptomyces thermoviolaceus was grown in a chemostat under conditions of glutamate limitation. The effects of growth rate on production of the antibiotic granaticin, extracellular protein and protease activity as components of secondary metabolism were studied at 37, 45 and 50 degrees C. The amount of each secondary metabolite synthesized was highly dependent on growth rate and temperature. Granaticin yields were highest at growth rates of 0.1 to 0.15 h-1 at 37 degrees C, 0.175 h-1 at 45 degrees C and 0.045 h-1 at 50 degrees C. Protease activity of culture supernatants responded to low nutrient concentration and/or low growth rate. Measurements of extracellular protein revealed complex changes in amount which were dependent on growth rate and temperature. At 45 degrees C and a growth rate of 0.15 h-1, biomass yield was highest between pH 5.5 to 6.5 whereas granaticin synthesis was low at pH 5.5 and rose to highest values at between pH 6.5 and 7.5.

Antibiotics, Antineoplastic↗

Survival of a plasmid-bearing strain of Bacillus subtilis introduced into compost.

Survival of Bacillus subtilis strain 168 containing plasmid pAB224, which carries a gene for tetracycline resistance, was studied in mushroom compost under mesophilic and thermophilic conditions. Stable populations of B. subtilis were maintained as spores in both sterile and fresh mushroom compost incubated at 37 degrees C. At 65 degrees C, the introduced B. subtilis populations declined during incubation but spores were still detectable after 28 d. Survival at the higher temperature was greater in fresh than in sterile compost. There was no apparent loss of plasmid pAB224 or plasmid-determined phenotype from the introduced B. subtilis population at either incubation temperature. The frequency of tetracycline resistance in the indigenous Bacillus population was very low (10(-5), but some tetracycline-resistant isolates contained plasmid DNA. Four plasmid DNA profiles were found associated with five Bacillus phenotypes, and some evidence for homology with pAB224 was found. However, pAB224 was found to be a suitable marker for release studies because it was easily recovered, readily distinguished from indigenous plasmids on agarose gels, and was maintained in compost-grown B. subtilis 168 in the absence of any selective pressure.

Bacillus subtilis↗

Hospital prescribing and usage of hypnotics and anxiolytics.

In-patient prescribing and usage of hypnotic and anxiolytic drugs were surveyed in a teaching hospital for 4 to 6 weeks. Twenty-one percent of admissions were prescribed these drugs which were predominantly benzodiazepines. Few patients (1.6%) were discharged with such prescriptions and subsequent usage in the community was similar to that before admission to hospital (6.1% and 6.4% respectively). In-patient consumption increased with patient age and both prescriptions and consumption were greater in women than men.

Anti-Anxiety Agents↗

Lack of effect of flosequinan on the pharmacokinetics of theophylline.

The pharmacokinetics of theophylline (240 mg) p.o. were studied before and after the administration of oral flosequinan for 14 days in 21 healthy volunteers using a randomised cross-over design. Comparisons of Cmax, tmax, AUC, CL of theophylline and urinary recovery of the parent drug and metabolites showed that flosequinan had no significant effect on the disposition of theophylline.

Administration, Oral↗

Haemophagocytic syndrome.

Two fatal cases of haemophagocytic syndrome diagnosed on the basis of autopsy findings at the Queen Elizabeth Hospital, Barbados, are presented. They were both young patients, a male 20 years of age and a female 28 years of age, with common clinical features of severe constitutional symptoms, pharyngeal haemorrhages, pancytopenia, and fever. The female patient had elevated titres to herpes simplex virus indicative of recent infection as well as postmortem evidence of overwhelming mixed bacteria sepsis. In both cases, histopathological studies showed lymphoid depletion and histiocytes displaying haemophagocytosis.

Adult↗

Enzymatic digestion, solid-phase extraction, and gas chromatography/mass spectrometry of derivatized intact oxazepam in urine.

Enzymatic digestion with beta-glucuronidase (EC 3.2.1.31) was used to release intact oxazepam from urine samples containing the d5-analog internal standard. The resulting specimens were extracted with Du Pont PREP Type W cartridge (processed by a PREP Automated Sample Processor), Bond Elut Certify, and J.T. Baker "spe" columns for comparison of the columns' extraction recovery and overall effectiveness. Methyl iodide/tetrahexylammonium hydrogen sulfate and N,O-bis(trimethylsilyl)trifluoroacetamide/trimethylchlorosilane (10 g/L) were used for the methylation and trimethylsilylation studies. We used a Hewlett-Packard HP 5790 mass-selective detector equipped with a 13-m J & W DB-5 column (5% phenyl polysiloxane phase) for gas chromatography/mass spectroscopy (GC/MS) analysis and the Thru-Put Target software package for data processing. After several exploratory experiments, we adopted the Du Pont PREP system methylation procedure because of its effective recovery, the superior stability of the derivatization product, the possibility of incorporating a clean-up step, and the potential for high throughput. The extraction recovery from a set of control samples was 87%. Coefficients of variation obtained for six replicates of GC/MS analysis and for the overall procedure were 1% and 3%, respectively. Excellent linearity was established in the 50-8000 micrograms/L concentration range studied. With the use of 3-mL samples, a 20-microL final reconstitution volume, oxazepam at 50 micrograms/L was easily detected under the adopted operation conditions.

Benzodiazepines↗

Purpura and dermal thinning associated with high dose inhaled corticosteroids.

OBJECTIVE: To assess the effect of high dose inhaled corticosteroids on skin. DESIGN: Cross sectional study of patients receiving treatment for chest diseases. SETTING: Outpatient chest clinic in a teaching hospital. PATIENTS: 68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES: Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS: Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION: Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids.

Administration, Inhalation↗

Morphological behavior of cultured bovine adrenal medulla capillary endothelial cells.

Bovine adrenal medulla capillary endothelial cells were isolated and cloned, and their morphological behaviors in vitro were examined. In the culture of primary or early passage, one type of colony formed intracellular lumina both on the dish and in the three dimensional collagen gel. Another type proliferated well and showed morphology ranging from slender-shape to cobblestone shape, and were easily cloned. Cloned cells which showed slender-shapes formed tubular network on plastic dish after addition of PMA, OAG or vanadate, and these cells also formed multicellular tubules in the three dimensional collagen gel. However, the formation of diaphragmed fenestrae by these slender-shape clones was rare. One clone which showed cobblestone shape formed diaphragmed fenestrae, when cultured on collagen gel for more than one month. Isolated colonies or clones showed heterogeneity of cell shape, angiogenic behaviors and fenestrae formation.

Adrenal Medulla↗

Lack of effect of co-trimoxazole on the pharmacokinetics and pharmacodynamics of nifedipine.

The pharmacokinetics of nifedipine and its primary oxidised metabolite, M-I were studied in nine healthy volunteers following a single oral dose of 20 mg nifedipine alone or after pretreatment with oral co-trimoxazole. Following pretreatment with co-trimoxazole, no significant effect was detected on maximum plasma concentration, elimination half-life, or area under the plasma concentration-time curve of either nifedipine or M-I, nor on the blood pressure response to nifedipine.

Adult↗

Ultrasound velocity in human fingernail and effects of hydration: validation of in vivo nail thickness measurement techniques.

Distal nail thickness was measured using an electronic micrometer and both distal and proximal nail ultrasound times were recorded in 20 volunteers (10 male, 10 female), aged 20-39. The fingernail ultrasound velocity was 2.26 X 10(3) m/s (subject range 2.03-2.69) (analysis of variance technique). The proximal ultrasound transit time was greater than distal ultrasound transit time. In three volunteers, five micrometer and one distal midline ultrasound measurement of five nails were repeated on 10 occasions over 2 weeks. For the micrometer readings the average coefficient of variation was 5.3% (SD +/- 2.4%), and for the ultrasound reading the average coefficient of variation was 4.0% (SD +/- 1.3%). To assess the influence of hydration, in five volunteers the distal nail micrometer thickness and the distal nail ultrasound transit time were measured on five nails before and after 30 min of immersion in water initially at 37 degrees C. The mean distal ultrasound transmission time increased from 0.20 +/- 0.04 microseconds to 0.22 +/- 0.04 microseconds (P less than 0.001) after water immersion. The micrometer measurements and ultrasound velocity did not change significantly (mean ultrasound velocity = 2.01 X 10(3) m/s before, 2.04 X 10(3) m/s after immersion).

Adult↗

The effects of nerve terminal activity on non-quantal release of acetylcholine at the mouse neuromuscular junction.

1. Local endplate depolarization induced by anticholinesterase application to mouse nerve-diaphragm preparations was taken as a measure of non-quantal release of acetylcholine. 2. Non-quantal acetylcholine release occurred within 20-60 s after anticholinesterase application, either spontaneously or evoked by nerve stimulation. Non-quantal release declined with time and disappeared after 3-5 min. 3. The amplitude of stimulation-evoked non-quantal release increased with the frequency of stimulation and was maximal at frequencies above 50 Hz. Two stimuli were sufficient to evoke the maximal effect. 4. Micromolar concentrations of atropine, pirenzepine and vesamicol reduced the amplitude and shortened the duration of non-quantal release. Oxotremorine (10(-8) M) enhanced the amplitude and ouabain (10(-4) M) prolonged the duration of non-quantal release. 5. Our results support the idea that the non-quantal release is due to the vesicular acetylcholine transport system which becomes transiently a part of the nerve terminal during exocytotic release of quantal acetylcholine.

Acetylcholine↗

Tissue spaces during development and regression of the decidual cell reaction in ovariectomized, steroid-treated mice.

Changes in the extracellular and blood spaces of the uterus were assessed from the distribution volumes of 51Cr-EDTA and 51Cr-labelled red blood cells during the development and regression of the artificially induced decidual cell reaction in ovariectomized, steroid-treated mice. The normally high values for uterine extracellular space (0.35-0.40 microliter/mg) fell to less than 0.20 microliter/mg in association with decidual growth. Uterine blood space increased from around 0.02 microliter/mg to 0.03-0.05 microliter/mg with decidual development. Induction of decidual regression by removal of s.c. progesterone implants caused a rapid decline in tissue blood volume to reach control values (0.01-0.02 microliter/mg) within 24 h and preceded any reduction in uterine weight. Uterine vascular permeability, as determined from the tissue accumulation of 125I-labelled human serum albumin, fell with a similar time course. Tissue extracellular space returned to the higher control values within 48 h of initiating decidual regression.

Animals↗

A phase II trial of recombinant human interferon-gamma and recombinant tumor necrosis factor in patients with advanced gastrointestinal malignancies: results of a trial terminated by excessive toxicity.

Recombinant human tumor necrosis factor and recombinant human interferon-gamma are two representatives of a novel class of antineoplastic agents. Evaluation of these agents in vitro has suggested that the combination would be more effective than either agent alone. A prior phase I study demonstrated that the maximum tolerated dose for each agent was 150 micrograms/m2/day for 5 days when administered concomitantly. Based on this experience, a phase II trial of patients with biliary tract, pancreatic, and colorectal cancer was planned. Our goal was to treat a minimum of 14 patients with each tumor type. However, in the first 13 patients entered into this trial the toxic effects at the starting doses of 125 micrograms/m2/day for 5 days for each agent were intolerable, with four patients unable to complete planned therapy. In this cohort of patients, no objective responses were observed. Further clinical investigation of this combination should consider alternative treatment schedules to reproduce the in vitro synergistic cytotoxicity of this combination while minimizing host toxicity.

Adolescent↗