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Biomedical subjects

R C Elliott

Publications and source records attributed to R C Elliott.

At least 37 records · Page 2Linked to original sources

Light effects on several chloroplast components in norflurazon-treated pea seedlings.

Changes occurring in several chloroplast components during Norflurazon-induced photobleaching of Pisum sativum seedlings were investigated. mRNA steady state levels of the chlorophyll a/b-binding protein of photosystem II, ferredoxin I, the small and large subunits of ribulose 1,5-bisphosphate carboxylase, and pEA214 and pEA207, two other light-responsive genes, were determined during chlorophyll photooxidation. Relative transcription rates were assayed in isolated nuclei. The results illustrate a complex set of interactions regulating expression of the nuclear and chloroplast genomes. Photobleaching was found to affect the expression of the various genes in different ways. While transcript levels of the chlorophyll a/b-binding protein decreased by more than 80% under photooxidative light conditions in carotenoid-deficient peas, levels of ferredoxin, the small and large subunits of ribulose 1,5-bisphosphate carboxylase, and pEA214 mRNAs were reduced by less than 50%. pEA207 mRNA levels, on the other hand, were resistant to the effects of photobleaching. Analyses of chlorophylls a and b and the chlorophyll a/b-binding protein suggest that accumulation of the protein and its mRNA are coordinated with chlorophyll abundance at several steps. In addition to post-transcriptional regulation at the level of mRNA and protein stability, there may exist coordination at the transcriptional stage.

Journal Article↗

Specificity of cotranslational amino-terminal processing of proteins in yeast.

Polypeptides synthesized in the cytoplasm of eukaryotes are generally initiated with methionine, but N-terminal methionine is absent from most mature proteins. Many proteins are also N alpha-acetylated. The removal of N-terminal methionine and N alpha-acetylation are catalyzed by two enzymes during translation. The substrate preferences of the methionine aminopeptidase (EC 3.4.11.x) and N alpha-acetyltransferase (EC 2.3.1.x) have been partially inferred from the distribution of amino-terminal residues and/or mutations found for appropriate mature proteins, but with some contradictions. In this study, a synthetic gene corresponding to the mature amino acid sequence of the plant protein thaumatin, expressed in yeast as a nonexported protein, i.e., lacking a signal peptide, has been used to delineate the specificities of these enzymes with respect to the penultimate amino acid. Site-directed mutagenesis, employing synthetic oligonucleotides, was utilized to construct genes encoding each of the 20 amino acids following the initiation methionine codon, and each protein derivative was isolated and characterized with respect to its amino-terminal structure. All four possible N-terminal variants--those with and without methionine and those with and without N alpha-acetylation--were obtained. These results define the specificity of these enzymes in situ and suggest that the nature of the penultimate amino-terminal residue is the major determinant of their selectivity.

Acetyltransferases↗

A reappraisal of the evidence for a direct action of tetraethylammonium on the chick biventer cervicis muscle equilibrated with lidocaine.

Contractures of the chick biventer cervicis muscle were recorded in vitro in response to exogenous acetylcholine (ACh) and to tetraethylammonium (TEA) and concentration response curves (CRC) produced for these drugs. In BVC muscles equilibrated with lidocaine (1.07 mM), physostigmine (3.63 microM) blocked TEA induced contractures in a reversible non-competitive manner. It had a similar action on ACh induced contractures. Lidocaine (1.07 mM) had no action on the ACh CRC except that it reduced the response to the highest concentration of ACh tested. The data of this and of previous experiments was analyzed and a theory proposed to account for TEA contractures. It suggested that background extravesicular ACh release results in the passage of K+ into the transverse tubular system (TT). In the presence of TEA blocking the K+ channels accumulation of K+ in the TT no longer occurs. Na+/K+ exchange is depressed in favour of Na+/Ca+ exchange and the resulting rise in intracellular Ca2+ acting on the sarcoplasmic reticulum leads to contraction. Lidocaine potentiates the contraction by blocking Ca2+ uptake into the sarcoplasmic reticulum.

Acetylcholine↗

The role of acetylcholine in tetraethylammonium induced contractures of the chick biventer cervicis muscle in the presence of lidocaine.

Lidocaine (0.92 mM) potentiated tetraethylammonium (TEA, 0.6-6 mM) induced contractures of the chick biventer cervicis muscle (BVC) in vitro. The dose ratio for TEA (EC50 in lidocaine/EC50 control) was 1.16 X 10(-3). Lidocaine (0.92 mM) blocked nerve and muscle action potentials in the BVC preparation, blocked slow fibre MEPPS, and blocked indirectly elicited muscle contraction. Lidocaine (0.92 mM) non-competitively blocked acetylcholine (ACh) induced contractures of the chick BVC. Gallamine competitively blocked ACh contractures (pA2 6.53) but produced only a relatively weak non-competitive block of TEA induced contractures in lidocaine. TEA induced contractures of the chick BVC in the presence of lidocaine probably do not involve ACh.

Acetylcholine↗

The isolation of a toxin from the dahlia sea anemone, Tealia felina L.

Gel chromatography with Dyematrex blue B gel and ion exchange chromatography with a methylcellulose cation exchange column have been used to isolate a toxin present in partially purified saline extracts of the dahlia sea anemone Tealia felina. Toxin activity was assessed by its histaminolytic activity. A ten-fold increase in activity per mg protein was achieved in these two steps. Final purification on a Sephacryl column yielded an apparently pure protein with a molecular weight of 7800. The amino acid composition of this compound was determined.

Amino Acids↗

Tetraethylammonium-methohexitone induced contractures and miniature end-plate potential discharge in the chick biventer cervicis muscle.

End-plate and miniature end-plate potentials (EPP, MEPP) were recorded in the chick biventer cervicis muscle in vitro. The control frequency of discharge of MEPPs was 5.97 +/- 1.04 min-1, n = 10. Methohexitone (8.8 X 10(-5) M) did not affect the frequency of MEPP discharge, but tetraethylammonium (TEA, 2.4-9.5 mM), reduced the frequency to 32.9 +/- 8.6% of the control. In the presence of neostigmine (3.3 X 10(-6) M) methohexitone (8.8 X 10(-5) M) reduced MEPP frequency to 38.7 +/- 5.4% of the control and TEA (2.4-9.5 mM) further reduced the frequency to 8.7 +/- 2.1% of the control. After a transient facilitation of the EPP, TEA (2.4-9.5 mM) in the presence of methohexitone (8.8 X 10(-5) M) and neostigmine (3.3 X 10(-6) M) markedly reduced EPP amplitude. The contractures which TEA produced in the presence of methohexitone were not due to an increase in the spontaneous release of vesicular ACh.

Animals↗

The action of intravenous anaesthetic and central depressant drugs on the contractures elicited by tetraethylammonium in the chick biventer cervicis muscle.

A group of intravenous anaesthetic drugs was compared with methohexitone sodium for their ability to potentiate tetraethylammonium induced contractures of the chick biventer cervicis muscle (TEA test). The equipotent concentrations in the TEA test were: methohexitone 8.8 X 10(-5) M, propanidid 1.78 X 10(-4) M, althesin 3.58 X 10(-5) M (in terms of alphaxalone), etomidate 1.6 X 10(-4) M, thiopentone 2.13 X 10(-5) M and valium 4.95 X 10(-5) M. There was no relation between activity in the TEA test and excitatory muscular activity reported clinically. The central depressant drugs ethyl alcohol and urethane also potentiated TEA but they were only active in high concentrations (10(-1) - 10(-2) M). alpha-Chloralose was inactive but paraldehyde (3.8 X 10(-3) M) actually reduced TEA induced contractures. Lipophilicity is only one factor in determining activity in the TEA test, the ability to block Ca2+ reuptake may also be important.

Alfaxalone Alfadolone Mixture↗

The influence of barbiturate drugs on tetraethylammonium induced contractures of the chick biventer cervicis muscle in vitro.

Methohexitone sodium (METHO) 8.8 X 10(-5) M markedly potentiates tetraethylammonium (TEA)-induced contractures of the chick biventer cervicis muscle in vitro, (Elliott, 1979). A group of barbiturates were compared with METHO for their ability to potentiate TEA induced contractures. The concentrations of TEA which produced a 50% maximum contracture (EC 50) in the presence of METHO (8.8 X 10(-5) M) and in the optimum potentiating concentrations of the other barbiturates were determined. The EC 50 ratios (= EC 50 METHO/EC 50 test drug) were: barbitone sodium 0.25, phenobarbitone sodium, 0.20, pentobarbitone sodium 0.90, thiopentone sodium, 2.43. The concentrations of the barbiturates used were: barbitone 3.1 X 10(-2) M, phenobarbitone 3.15 X 10(-3) M, pentobarbitone 6.04 X 10(-4) M, thiopentone 1.89 X 10(-4) M. The EC 50 ratios were adjusted by dividing by the ratio [test barbiturate]/[METHO]. The adjusted ratios gave the following potencies (METHO = 1), barbitone 7.13 X 10(-4), n = 6, phenobarbitone 5.58 X 10(-3), n = 8, pentobarbitone 1.33 X 10(-1), n = 6, thiopentone 1.13, n = 6. The potencies correlate well with the partition coefficients of the barbiturates between cell membranes and buffer (P m/b). The regression y = 1.49x -3.12, where y = log (adjusted ratio) and x = log (P m/b) fits data with a correlation coefficient of 0.99.

Anesthetics↗

Carbachol-methohexitone interactions at the chick neuromuscular junction: experiments with the moving fluid electrode technique.

The moving fluid electrode was used to record simultaneously the depolarization and contracture responses produced by drug action. Carbachol (CCh) (5.5 X 10(-6)-5.5 X 10(-4)M) acetylcholine (ACh) (5.5 X 10(-6)-1.1 X 10(-2) M) produced large depolarization and contracture responses in the isolated chick biventer cervicis (BVC) muscle. These responses were greatly reduced by methohexitone (8.8 X 10(-5) M). The concentration-response curves for ACh and carbachol in the control Krebs solution were shifted in the presence of methohexitone to the right in a non-competitive manner. The present results indicate that both ACh and carbachol act postjunctionally by depolarizing the membrane and producing contractures in the chick biventer cervicis muscle.

Acetylcholine↗

The actions of tetraethylammonium at the neuromuscular junction.

1. Tetraethylammonium (TEA) produces contractures in slow muscle fibres of the chick and the guinea-pig. 2. These contractures probably involve (a) the facilitation of the release of acetylcholine by TEA (b) direct stimulant action of TEA on the post-synaptic membrane with little accompanying depolarization. 3. Since microelectrode studies on fast twitch fibres indicate that TEA exerts a blocking action on the Na+/K+ ion channel of the end-plate it may be that TEA produces its direct contracture-inducing action in slow fibres by increasing Ca2+ influx.

Animals↗

The partial purification and bioassay of a toxin present in extracts of the sea anemone, Tealia felina (L.).

1. Column chromatography with Agarose A50m followed by Sephadex G100 was used to separate a fraction (extract II) in the molecular weight range 12,000 to 14,000 daltons from saline extracts of the sea anemone, Tealia felina. 2. Extract II inhibited histamine-induced contractions of the guinea-pig ileum and produced haemolysis of human blood, effects on which bioassays were based. 3. The potency of extracts was assayed. A standard unit of activity (= AU) was defined such that 100 AU produced 90% inhibition of histamine-induced contractions of the guinea-pig ileum after 30 to 35 min exposure. 4. The relationship between activity of the extracts measured on the ileum and their haemolytic activity was studied, providing a second assay method based on the latter property. 5 Based on values from both methods of assay, the calculated yield in AU at the end of the separation procedure was 0.53 AU for each AU present in the original extract. In crude extract there were 5.0 AU/mg dry weight and 36.7 AU/mg protein, and after separation (extract II) there were 11.2 AU/mg dry weight and 312.2 AU/mg protein. 6 The acute LD50 values determined in mice (i.v.) were: for crude extract 124 mg/kg for extract I, 76 mg/kg and for extract II, 69 mg/kg. 7 Extract II (0.18 to 0.72 AU/ml) produced a slowly developing contraction of guinea-pig ileum. Indomethacin (2.8 x 10(-5) M) substantially reduced this response. 8 Extract II (0.03 AU/ml) reduced the contractile response of the guinea-pig ileum to acetylcholine by 39 +/- 8%, n = 6, and the response to histamine by 26 +/- 6.6%, n = 6. The response to 5-hydroxytryptamine (5-HT) was not reduced by 0.08 AU/ml of extract II, a concentration that actually increased the contractile response to KC1 by 32 +/- 11.2% n = 7. 9 It is proposed that for future work on the extract a new AU should be used. This AU is defined such that 50 AU produce 50% inhibition of histamine-induced contractions of the guinea-pig ileum after 30 to 35 min exposure.

Acetylcholine↗

Scars without wounds: spectrum of delayed manifestations of histoplasmosis outside of the endemic area.

This short series represents a spectrum of histoplasmosis usually described only in places where the infection is nearly universal. In fact, most of the patients in this series were born in such places (17 of 19 patients with complicated presentations; 2 had recent suspicious exposures). As young adults, they had moved away to pursue military life, usually in coastal areas where the evidence of infection with H. capsulatum is a statistical rarity. The implications of these observations are straightforward. At the clinical level, they focus on histoplasmosis as a possible cause of pulmonary, mediastinal, or other lesions of obscure etiology, whether or not the patient has recently lived in "the endemic area". The simple determination of CF gamma titers may heighten the index of suspicion, especially when not confounded by skin testing with histoplasmin, a practice which rarely provides useful information. [Table: see text] With regard to pathogenesis, it seems noteworthy that common form of histoplasmosis was not seen in this brief experience. That is the "marching cavity" described by Goodwin and Des Prez, and other forms of chronic cavitary disease. The absence of such lesions is consonant with the view that they require continuous exogenous infection for their development. As for the forms of histoplasmosis which were seen in this series, it appears that most of the illnesses developed outside of what is usually considered endemic areas. The term endemic, as construed medically, has been defined as "restricted to and constantly present in a particular country or locality". Such a construction is unduly pedantic and rigid for clinicians. A more probabilistic view is needed, with attention to the possible role of inapparent infection early in life and of environmental foci of infection in places where the organism is not notoriously present. The mobile nature of our society makes it likely that the radiographic manifestations of once-regional diseases such as this one will be encountered more generally than in the past.

Adolescent↗

Contractures elicited by tetraethylammonium in avian muscle treated with methohexitone.

1 The chick biventer cervicis muscle immersed in methohexitone (8.8 x 10(-5) M) responded to tetraethylammonium with contractures which were dose-related. The ED50 for tetraethylammonium was 2.1 x 10(-3) M. 2 In the absence of methohexitone, tetraethylammonium produced contractures only at much higher concentrations: these contractures were accompanied by fasciculations and neuromuscular block of the twitch fibres. 3 The contractures produced by tetraethylammonium in the presence of methohexitone were not reduced by exposure to botulinum toxin which eliminated all response of the muscle to indirect stimulation. 4 Tubocurarine (1.2 x 10(-6) M) displaced the dose-response curve for tetraethylammonium-methohexitone-induced contractures to the right. The dose-ratio was 15.63 +/- 1.98. 5 Physostigmine (1.8 x 10(-6) M) potentiated the activity of tetraethylammonium-methohexitone 3.26 or 3.84 fold, depending on the method of calculation used. 6 Physostigmine potentiated contractures elicited by indirect repetitive stimulation 4.8 to 6.0 fold more than it potentiated contractures due to tetraethylammonium-methohexitone. 7 It is concluded that in the presence of methohexitone, tetraethylammonium produces contractures of the chick muscle by releasing acetylcholine but also by a direct agonist action on the cholinoceptor.

Animals↗

Bronchiolar carcinoma: report of 11 cases and review of the literature.

Eleven cases of bronchiolar carcinoma seen between 1970 and 1975 are reviewed. Roentgenographic manifestations at the time of initial examination included single peripheral nodules, multiple nodules, irregular cavities and a persistent infiltrative form. Microscopic tissue examinations showed two patterns of tumor growth: a papillary form resembling tall columnar cells extending along but not invading the alveolar septal walls and a cribriform pattern represented by inflammatory thickening of the alveolar septal walls and pleomorphic cellular proliferation within luminal spaces. The papillary form was associated with the cavitary lesions. Long term survival is dependent on early recognition of the single peripheral nodule, cavity or small persistent infiltrative form managed by a thoracotomy and lobectomy.

Adenocarcinoma, Bronchiolo-Alveolar↗

A study of co-positivity of three multipuncture techniques with intradermal PPD tuberculin.

One hundred thirty-five patients with a reaction of 10 mm or more of induration to 5 TU of intradermal PPD were simultaneously tested with 3 multipuncture techniques to determine the copositivity of the multiple puncture methods with the Mantoux method. Of the 3 multipuncture preparations used (Tine Test, Aplitest, and Mono-Vacc), the Mono-Vacc had 2 (1.5 per cent) false-negative result after 48 hours with only one remaining negative result after 72 hours; whereas the Tine-Test had 21 (15.5 per cent), and the Aplitest had 13 (9.6 per cent) false-negative reactions after 48 hours. Vesicular eruptions were not a commonly noted reaction to the multipuncture preparations. Of the 3 multipuncture preparations commercially available, Mono-Vacc is the preferred reagent because of its significantly lower incidence of false-negative reactions.

Adolescent↗