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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 253 records · Page 14Linked to original sources

In-vitro production of nitrosamines by bacteria isolated from the operated stomach.

Evidence is presented of in-vitro catalysis of nitrosation by organisms isolated from the hypoacidic operated stomach. Subjects taking part in a prospective study of potential premalignancy after benign ulcer surgery underwent endoscopy, and samples of gastric juice were obtained aseptically. The organisms present were identified using the API system and tested for their ability to catalyse the nitrosation of the secondary amine, morpholine, at neutral pH and 37 degrees C. Four of the five species tested were found to be capable of the catalysis. Cellular disruption and denaturation of protein abolished the catalytic ability, suggesting that the catalysis is mediated by an enzymic system. Osmotic shock experiments indicate that the enzyme site may be on the inner membrane.

Female↗

Involvement of the Ca2+-dependent K+ channel activity in the hyperpolarizing response induced by epidermal growth factor in mammary epithelial cells.

Epidermal growth factor (EGF) induces a hyperpolarizing response of 5-20 mV amplitude in mouse mammary epithelial cells in culture. The amplitude of the hyperpolarizing response was reduced by more than 60% within several minutes after addition of blockers of voltage and/or Ca2+-dependent K+ channels such as tetraethylammonium (7 mM) or quinine (0.29 mM). Both nifedipine (0.15 mM), a blocker of the Ca2+ channel, and ruthenium red (2 mM), an inhibitor of the Ca2+-binding site, also reduced the amplitude of the hyperpolarizing response by more than 60%. The Ca2+ ionophore, A23187 (3.8 microM), induced a large hyperpolarization, which was 25-40 mV and lasted about 3 min. These data suggest that activity of the Ca2+-dependent K+ channel was involved in the EGF-induced hyperpolarizing response of the mammary epithelial cells.

Animals↗

The anion selectivity of the gamma-aminobutyric acid controlled chloride channel in the perfused spinal ganglion cell of frog.

The selectivity of the GABA-controlled Cl- channel in the membrane of the dorsal root ganglion cell of the frog has been measured in internally perfused cells by means of current and voltage clamp. When Cl- was replaced by various anions, the 10(-5) or 10(-4) M GABA-induced reversal potentials (EGABA) for Br-, I-, NO3-, ClO4-, SCN-, BF4- and ClO3- were more negative than that for Cl-, despite the fact that, in solution, the test anions are either larger than or similar in size to Cl-.

Animals↗

Induction of distinct types of spontaneous electrical activities in mammary epithelial cells by epidermal growth factor and insulin.

Electrophysiological measurements of the membrane potentials of mouse mammary epithelial cells in primary culture revealed the presence of spontaneous-oscillating-hyperpolarizing potentials in cells incubated with epidermal growth factor. The hyperpolarizing potentials were 5-20 mV in amplitude and about 10 sec in duration. The peak height of the response was reduced by hyperpolarization, and the input membrane resistance decreased during the response. The response was probably due to activation of K+ channels. The latency period for the epidermal growth factor induction of the hyperpolarizing potential was approximately 3 hr. In contrast, insulin induced spontaneous-depolarizing potentials that were about 5 mV in amplitude and 1 sec in duration. The depolarizing potentials were attributed to activity of ion channels, since the peak height was dependent on the membrane potential and the depolarizing potential was accompanied by a decrease of input membrane resistance. The time lag for the induction of the depolarizing potential was 6-12 hr. Other hormones involved in mammary cell differentiation, such as cortisol and prolactin, neither induced the depolarizing potentials nor changed the induction of depolarizing potential by insulin. In addition, other growth factors, such as nerve growth factor and fibroblast growth factor, elicited no electrical activity.

Animals↗

Meiosis can induce recombination in rad52 mutants of Saccharomyces cerevisiae.

The RAD52 and RAD50 genes have previously been shown to be required for normal meiotic recombination and for various types of recombination occurring in mitotic cells. Recent evidence suggests that rad52 mutants might be defective in an intermediate recombination step; we therefore examined recombination during meiosis in several rad52 mutants at several different loci and in genetic backgrounds that yield efficient sporulation and synchronous meiosis. Similar to previous reports, spores from rad52 diploids are inviable and meiotic recombination is greatly reduced by rad52 mutations. However, intragenic recombinants were detected when cells were plated on selective media during meiosis; rad52 mutants experience induction of recombination between homologues under these special conditions. The frequencies of recombination at four loci were considerably greater than the mitotic controls; however, they were still at least 20 times lower than corresponding Rad+ strains. The prototrophs induced by meiosis in rad52 mutants were not typical meiotic recombinants because incubation in nutrient-rich medium before plating to selective medium resulted in the complete loss of recombinants. We propose that previously observed single-strand breaks that accumulate in rad52 mutants may be associated with recombinational intermediates that are resolved when cells are returned to selective mitotic media and that the meiosis-induced recombination in rad52 cells does not involve double-strand breaks.

DNA Transposable Elements↗

Endemic Burkitt's lymphoma: phenotypic analysis of tumor biopsy cells and of derived tumor cell lines.

Tumor cells from 10 patients with Epstein-Barr virus-positive endemic Burkitt's lymphoma (BL) have been examined for cell surface phenotype, both at the biopsy stage and during BL cell line outgrowth in vitro, the cultures being followed for up to 150 passages. In all 10 cases, the biopsy cells showed coexpression of the common acute lymphoblastic leukemia antigen (CALLA) and of the BL-associated glycolipid antigen (BLA) with no accompanying expression of several "lymphoblastoid" cell surface markers defined by selected monoclonal antibodies. During cell line establishment and in vitro passage, the individual BL cell lines showed different degrees of progression toward a more "lymphoblastoid" cell surface phenotype, some even losing CALLA and BLA expression while retaining the chromosomal translocations indicative of their malignant origin. This differential capacity for phenotypic progression in vitro explains much, if not all, of the heterogeneity of the BL cell phenotype apparent from many previous studies with panels of long-established lines. Such heterogeneity in vitro belies the true homogeneity of the tumor cell phenotype in vivo.

Antibodies, Monoclonal↗

Effect of two new antisecretory drugs on fluid and electrolyte transport in a patient with secretory diarrhoea.

The effect of oral lidamidine hydrochloride and subcutaneous long acting somatostatin analogue, SMS 201-995, on stool output and salt and water transport in the small intestine was investigated in a patient with gross secretory diarrhoea caused by a vasoactive intestinal polypeptide (VIP) secreting tumour in the liver. Transport in the jejunum and ileum were assessed by steady state perfusion techniques. Under basal conditions, the patient was absorbing fluid and electrolytes from the jejunum and ileum, but at rates that were abnormally low. Lidamidine had no effect on either intestinal transport or stool frequency and output. SMS 201-995 increased intestinal absorption in the jejunum and ileum, reduced plasma VIP concentrations, daily stool frequency and weight, and enabled the patient to resume a normal diet without oral or intravenous fluid and electrolyte supplements. After two months of treatment, medical control was becoming increasingly difficult and stool output had risen again to 2 litres per day. Surgical resection, fortunately, was possible and led to resolution of symptoms and normal plasma VIP concentrations.

Adult↗

Poorly differentiated squamous carcinoma of the bronchus: a light and electron microscopic study.

As there is little published information on the ultrastructure of poorly differentiated squamous carcinoma of the bronchus 18 examples of this tumour were studied. On light microscopy 10 of the tumours contained foci of keratinisation or intercellular bridges and therefore fulfilled the World Health Organisation's diagnostic criteria. In eight these features were absent, but the overall appearance was sufficiently squamoid to preclude their placement in any other category. On electron microscopy many cells showed the characteristic desmosomes and tonofilament of of squamous carcinoma, but there were also areas of adenodifferentiation. The ultrastructure of both light microscopic groups was identical. In conclusion, this type of tumour is dimorphic with characteristics of adenocarcinoma and squamous carcinoma on electron microscopy. Keratinisation and bridges are not essential diagnostic criteria: the overall pattern and cellular morphology are more important.

Adenocarcinoma↗

Scar adenocarcinoma of the lung: a light and electron microscopic study.

Five well differentiated peripheral adenocarcinomas of the lung were investigated, using light and electron microscopy. Each tumour contained a central nidus of fibrous tissue and fulfilled the criteria for "scar cancer." One tumour also had a focus of lamellated collagenous tissue, suggestive of an old tuberculous granuloma. Electron microscopy showed the features of Clara cells, with characteristic dense bodies in the apical cytoplasm and scattered microvilli on the luminal surface. It was concluded that this variant of scar cancer was a carcinoma of Clara cells, which was sufficiently distinctive in appearance to be recognised on light microscopy alone. It remains uncertain, however, whether the central fibrous area is a desmoplastic response to tumour growth or a pre-existing scar.

Adenocarcinoma↗

Thiamine blockade of neuromuscular transmission.

The effects of thiamine on neuromuscular transmission were studied. Thiamine (0.2-2 mM) decreased the quantal height (q) of the evoked end-plate current (EPC). In the presence of 2 mM thiamine, the shape of the decay phase of the EPC remained exponential but the decay time constant increased dramatically. Thiamine changed the EPC height/holding potential and log (EPC decay time constant)/holding potential relationships from linear to non-linear. The reversal potential and the rate of rise of the EPC were unaffected. Analysis of the ACh-induced noise revealed that thiamine increased the mean channel lifetime and decreased the single channel conductance. Under normal conditions, the ACh-induced single channel conductance had no membrane voltage dependency, while thiamine caused the single channel conductance to decrease with hyperpolarization. The effects of thiamine could be explained in computer simulation of the peak EPC/membrane potential relationship by the assumption that thiamine prolonged the channel lifetime and decreased the single channel conductance with hyperpolarization. It is concluded that thiamine modifies the kinetics of ACh-receptor ion channel complex and that this effect is dependent on the membrane voltage.

Animals↗

Dietary sodium and arterial blood pressure: evidence against genetic susceptibility.

Thirty five subjects with both parents in the top third of their age specific blood pressure distributions and 31 subjects with both parents in the bottom third of their blood pressure distributions restricted their intake of sodium for eight weeks while taking part in a double blind, randomised crossover trial of supplements of sodium and placebo. A comparison of two periods of four weeks at different intakes of sodium showed no differences in blood pressure in either the groups as a whole or the subgroups who complied best with the diet and tablets. In the compliant subgroups mean urinary sodium excretions were above 120 mmol(mEq) and below 50 mmol/day. The study provides evidence against the hypothesis that people with a family history of high blood pressure are more susceptible in their blood pressure response to dietary sodium.

Adult↗

Effects of guanethidine and phenethylguanidine on the frog neuromuscular junction.

The effects of two guanidine derivatives, guanethidine and phenethylguanidine (2-phenyl-ethyl-guanidine), on neuromuscular transmission in the sartorius nerve-muscle preparation of the frog, Rana pipiens, were investigated. Both compounds decreased the peak height of the evoked end-plate current (EPC). The decay of the EPC was changed from a single exponential to a double exponential. The effects of both compounds on the EPC peak height increased with hyperpolarization, and the peak EPC/membrane voltage relationship thus became non-linear. The absence of an effect on the mean quantal content (m) indicated that the two compounds acted postsynaptically. The power spectrum of the ACh-induced noise was changed by guanethidine from a single Lorentzian to a double Lorentzian curve. The single channel conductance was decreased with hyperpolarization. It was concluded from these observations that guanethidine is an open channel blocker. Phenethylguanidine shifted the cut-off frequency of the ACh-induced noise to a higher frequency. However, the power spectrum showed only a single Lorentzian, and there was a lack of low frequency component in the power spectrum, which was expected from the decay phase of the EPC. The single channel conductance decreased, but in contrast to the case of guanethidine, there was no voltage dependency. The possible mechanism of action of phenethylguanidine is discussed.

Acetylcholine↗

Effects of hycanthone on the neuromuscular transmission.

The effects of the antischistosomal drug, hycanthone, on the synaptic transmission at the frog neuromuscular junction were studied. The mean quantal content increased in the presence of 20 microM hycanthone. The amplitude of the miniature end-plate current was unaffected by 20 microM hycanthone, while 2 microM hycanthone decreased the ionophoretic ACh response (ACh induced current). The decay time constants of the evoked end-plate current and the miniature end-plate current were increased with 1-5 microM hycanthone, but were decreased at concentrations over 20 microM. Analysis of the ACh induced noise revealed that 1 microM hycanthone slightly increased the channel lifetime whereas the single channel conductance was not affected. It was concluded that the primary site of action of hycanthone is the 'transient state' or ACh bound but closed conformation of the ACh receptor ion channel, but this drug also has other sites of action (presynaptic nerve terminal and open conformation of ACh receptor-ion channel complex).

Animals↗