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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 271 records · Page 15Linked to original sources

Mixed mesodermal sarcoma of the ovary. Treatment with combination radiation therapy and chemotherapy.

Twenty patients with mixed mesodermal sarcoma of the ovary treated at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas are reviewed. This report focuses on 12 patients treated post-operatively with combination radiation therapy and chemotherapy with vincristine, dactinomycin, and cyclophosphamide (VAC). There were 4 patients achieving complete tumor control, including one who is alive without disease beyond 5 years and 3 who died of unrelated causes without disease at autopsy. One other patient had a significant disease-free interval of 18 months. Compared to previous reports, combination radiation and VAC chemotherapy appears effective in this disease. Due to the observed myelosuppression and gastrointestinal and neurologic toxicities, however, treatment modifications have been recommended.

Adult↗

Dietary sodium restriction for mild hypertension in general practice.

Eighteen patients with stable mild hypertension (mean blood pressure 144/93 mm Hg) restricted their sodium intake for eight weeks while taking part in a double blind randomised crossover trial of slow sodium and placebo tablets. Mean 24 hour urinary sodium excretion was 143 mmol(mEq) during the period on slow sodium and 87 mmol during the period on placebo. Five patients were unable to reduce their sodium intake below 120 mmol, but the others had a mean 24 hour urinary sodium excretion of 59 mmol during the period on placebo. There was no significant difference in blood pressure between the slow sodium and placebo treatment periods, although the study had a power of 99% to detect a difference of 5 mm Hg in mean arterial pressure between the two periods. Moderate dietary sodium restriction does not lower blood pressure in patients with this degree of hypertension.

Adult↗

Immunofluorescent evidence for exocytosis and internalization of secretory granule membrane in isolated chromaffin cells.

Cultured bovine adrenal medullary chromaffin cells were stimulated with the secretogogues Ba2+ or carbamyl choline plus Ca2+ in the presence of a monospecific rabbit IgG fraction directed against bovine dopamine beta-hydroxylase. The anti-dopamine beta-hydroxylase was labeled either with fluorescent protein A or with a fluorescent second antibody to rabbit IgG. Stimulation produced a patchy cell surface distribution of fluorescence. There was no noticeable internalization of the fluorescence for up to 2 h. In similar experiments using fluorescent monovalent fragments (Fab) of the same monospecificidopamine-beta-hydroxylase IgG, a more uniform distribution of the fluorescence was observed. A few min after a 5 min period of stimulation with Ba2+, the fluorescence appeared to be on or near the cell surface; however, after 20 min or more it was distributed throughout the cytoplasm except that the cell nuclei were not labeled. Thus, dopamine beta-hydroxylase which appeared on the cell surface as a consequence of exocytosis was internalized in the presence of monovalent antibody fragments, but not in the presence of the divalent (polyclonal) antibody, presumably because endocytosis of dopamine beta-hydroxylase was inhibited by crosslinking of the dopamine beta-hydroxylase molecules. The internalized anti-dopamine beta-hydroxylase Fab fragments were found to reappear on the cell surface during a second secretory response. It is concluded that the interior of the chromaffin granule membrane, for which dopamine beta-hydroxylase is a marker, becomes exposed on the surface of the cell during secretion and that the membrane is then retrieved back into the cell where it can be re-used in a further secretory cycle.

Animals↗

The effects of nalidixic acid on respiratory activity of asynchronous and synchronous cultures of Alcaligenes eutrophus.

Nalidixic acid inhibited DNA synthesis and cell division during asynchronous growth of Alcaligenes eutrophus but treated cells continued to grow as monitored by A550, respiratory activity and cell volume. Differential effects on cell division were seen when the antibiotic was added at different times during synchronous growth. The earlier in the cell cycle the time of addition the greater the inhibition of cell division. These results suggests that chromosome replication is confined to the first half of the cell cycle in A. eutrophus grown at 30 degrees C. Respiration rates of cells selected by continuous-flow centrifugation and immediately treated with nalidixic acid increased in a stepwise fashion. These steps were similar to those observed in untreated control cells and imply that the DNA-division cycle is not the causal factor for the periodicities in respiration rates and ATPase activity that have been previously reported in this bacterium.

Alcaligenes↗

Reproducibility of saliva and plasma theophylline levels following single dose administration of two sustained release preparations.

1 Concomitant saliva and plasma theophylline concentrations were measured in six healthy male volunteers following single dose administration of two sustained release preparations (Nuelin SA and Phyllocontin Continus). 2 Using mean values, a good correlation was obtained between saliva and plasma drug concentrations. Prediction of plasma values using individual saliva was poor and varied widely. The ratio of saliva to plasma concentrations in the same individual, assessed under standardised conditions, was not always reproducible.

Adult↗

The comparative bioavailability of slow release oral theophylline preparations.

Plasma concentrations of theophylline were determined in healthy volunteers following a single oral dose of six slow release preparations, immediately following a standard breakfast. There were no significant differences between the different preparations. The time taken to reach maximum plasma concentration, tmax, was found to be longer than in previous studies in which the drug was administered on an empty stomach.

Administration, Oral↗

Voltage-dependent drug blockade of L-glutamate activated channels of the crayfish.

The actions of d-tubocurarine (d-TC) and local anaesthetics on the L-glutamate activated channel at the voltage-clamped crayfish neuromuscular junction were studied. The effect of d-TC and local anaesthetics on the dose-response relationship between ionophoretically applied L-glutamate and synaptic current suggested that both acted as non-competitive inhibitors. The amount of inhibition was voltage dependent, and increased as the membrane potential was hyperpolarized. This voltage-dependent block was also manifest in a flattening of the I-V relationship between L-glutamate induced current and membrane potential in the presence of d-TC. However, the reversal potential for the L-glutamate activated channel was not affected; it was about +7 mV in both the presence and absence of d-TC. The neurally evoked excitatory post-synaptic current (e.p.s.c.) was depressed in the presence of these drugs and this effect was also voltage dependent. The time course of the e.p.s.c. was affected, but less so than expected if the L-glutamate activated channel were identical to the channel opened by acetylcholine at the vertebrate neuromuscular junction. Possible reasons for this discrepancy are discussed.

Animals↗

Exaggerated circadian variation in basal thyrotropin (TSH) and in the dopaminergic inhibition of TSH release in pathological hyperprolactinemia: evidence against a hypothalamic dopaminergic defect.

In order to delineate more accurately the dopaminergic control of anterior pituitary function in normal subjects and in patients with pathological hyperprolactinemia, we investigated the nature of the circadian variation in the dopaminergic inhibition of TSH release in such subjects. Ten euthyroid women with hyperprolactinemia due to presumed PRL-secreting microadenomas (aged 18-60 yr) were compared with 11 normal, euthyroid women (aged 18-32 yr). Each received the dopamine receptor blocking drug domperidone (10 mg, iv) at 1100 and 2300 h (tests randomized and separated by at least 1 week). Blood was sampled 10, 20, 30, 45, and 60 min after drug administration. Normal women had a greater TSH response to domperidone and, hence, greater dopaminergic inhibition of TSH release at 2300 than at 1100 h (sum of TSH increments; mU/liter mean +/- SE, 8.5 +/- 1.3 vs. 4.8 +/- 0.5, P less than 0.01), whereas there was no difference in the dopaminergic inhibition of PRL release at each time of day. Hyperprolactinemic women also had a significantly greater TSH response to domperidone at 2300 than at 1100 h (42.0 +/- 10.2 vs. 19.1 +/- 2.8, P less than 0.001). The hyperprolactinemic women had a greater TSH response to domperidone than normal women at each time of day studied (1100 h, 19.1 +/- 2.8 vs. 4.8 +/- 0.5, P less than 0.001; 2300 h, 42.0 +/- 10.2 vs. 8.5 +/- 1.3, P less than 0.001). The incremental PRL responses to domperidone were significantly less in hyperprolactinemic than in normal women and did not differ at each time of day. In conclusion, the circadian change in the dopaminergic inhibition of TSH secretion is specific for TSH and not PRL. This indicates that the dopaminergic control of TSH and PRL secretion can be dissociated in normal subjects. Second, hyperprolactinemic women with presumed PRL-secreting microadenomas had qualitatively normal but quantitatively exaggerated circadian pattern of dopaminergic inhibition of TSH release. These data argue against a hypothalamic dopaminergic defect in hyperprolactinemia and support the view that the established dopaminergic defect in the inhibition of PRL release is related specifically to PRL control and may well be at the anterior pituitary level.

Adenoma↗

Structural variation in the named bronchi of the left lung. A morphometric study.

In order to establish whether or not the named bronchi of the left lung differ structurally from each other, their proportions of cartilage, gland and muscle in normal and chronic bronchitic patients were measured. In the normal subject the lower lobe bronchus contains proportionally more muscle than either the upper lobe bronchus or the segmental bronchi. Its proportion of cartilage is less than that of the main and upper lobe bronchi, and in this respect it is similar to the segmental bronchi. The proportions of gland in the main, upper and lower lobe bronchi are the same. There is no difference between the tissue proportions of the segmental bronchi of the upper and lower lobes. In chronic bronchitics the proportion of gland is increased, and in many cases there is also an increase in muscle. The relatively high proportion of muscle in the lower lobe bronchus is no longer apparent, and its proportion of cartilage is greater than in the normal subject. The main and upper lobe bronchi contain a higher proportion of gland than the lower lobe bronchus and the segmental bronchi. The proportions of the components in the upper and lower segmental bronchi are again similar. It is concluded that in the left lung the tissue proportions of the named bronchi vary. In particular, the normal lower lobe bronchus is characterized by a relatively high percentage of muscle, and a similar cartilage content to the segmental bronchi. Care is therefore needed in selecting airways for morphometric studies.

Aged↗

Cytochrome a620 in Tetrahymena pyriformis. Reactions with carbon monoxide and oxygen at subzero temperatures and photochemical action spectra.

1. Mitochondria-enriched fractions of the ciliate protozoan Tetrahymena pyriformis ST contained CO-reacting cytochromes b560 and a620. 2. A non-photodissociable oxygen-containing compound of cytochrome a620 was formed in whole cell suspensions at -114 degrees C after photolysis of CO in the presence of 200 microM-O2. 3. Electron transport, indicated by the oxidation of cytochrome a620 and cytochrome c, occurred at temperatures higher than -72 degrees C. 4. Photochemical action spectra for the relief of respiratory inhibition of whole cells by CO obtained by using a liquid dye laser indicate that the only CO-reacting terminal oxidase detectable was cytochrome a620. 5. It is concluded that the alternative electron transport chains in this organism utilize non-cytochrome terminal oxidases.

Carbon Monoxide↗

The ionic selectivity of two voltage activated channels and an acetylcholine activated channel in an Onchidium neuron.

1. The selectivities of the ion channels underlying the action potential and the hyperpolarizing response to acetylcholine of the GH cell of Onchidium have been analysed. 2. The rising phase of the action potential is due to an increase in the permeability of the membrane to both Na+ and Ca2+. The Na+ channel is permeable to Li+ and is somewhat permeable to formamidinium, guanidinium and ammonium ions. The Ca2+ channel is permeable to Sr2+ and Ba2+, but not to Mn2+ and Mg2+. 3. The Cl- channel operated by ACh is permeable to chlorate, but not to formate and propionate ions. 4. The selectivities of these channels are similar to those of a number of other channels in other organisms.

Acetylcholine↗

Evidence for the presence of two terminal oxidases in the trypanosomatid Crithidia oncopelti.

Increasing concentrations of cyanide inhibited the respiration of whole cells of Crithidia oncopelti in a biphasic fashion. Approximately 80% inhibition was attained with 40 microM-KCN. No further inhibition occurred until the concentration of KCN reached approximately 200 microM. Thereafter inhibition rose gradually to 100% at 1500 microM-KCN. Difference spectra revealed the presence of two CO-reacting haemoproteins. These were shown to be two different functional oxidases by photochemical action spectra obtained by using laser light. One oxidase was identified as cytochrome a + a3 whilst the other had the properties of cytochrome o. Both oxidases could be detected in cells at all stages of growth by the above methods.

Animals↗