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Biomedical subjects

A R Butler

Publications and source records attributed to A R Butler.

At least 19 recordsLinked to original sources
PubMed1992

Iron-sulphur cluster nitrosyls, a novel class of nitric oxide generator: mechanism of vasodilator action on rat isolated tail artery.

1. Two iron-sulphur cluster nitrosyls have been investigated as potential nitric oxide (NO.) donor drugs (A: tetranitrosyltetra-mu 3-sulphidotetrahedro-tetrairon; and B: heptanitrosyltri-mu 3-thioxotetraferrate(1-)). Both compounds are shown to dilate precontracted, internally-perfused rat tail arteries. 2. Bolus injections (10 microliters) of compound A or B generate two kinds of vasodilator response. Doses below a critical threshold concentration (DT) evoke transient (or T-type) responses, which resemble those seen with conventional nitrovasodilators. Doses > DT produce sustained (or S-type) responses, comprising an initial, rapid drop of pressure, followed by incomplete recovery, resulting in a plateau of reduced tone which can persist for several hours. 3. T- and S-type responses are attenuated by ferrohaemoglobin (Hb) and by methylene blue (MB), but not by inhibitors of endothelial NO. synthase. Addition of either Hb or MB to the internal perfusate can restore agonist-induced tone when administered during the plateau phase of an S-type response. Moreover, subsequent removal of Hb causes the artery to re-dilate fully. 4. We conclude that T- and S-type responses are both mediated by NO.. It is postulated that S-type responses represent the sum of two vasodilator components: a reversible component, superimposed upon a non-recoverable component. The former is attributed to free NO., preformed in solution at the time of injection; and the latter to NO. generated by gradual decomposition of a 'store' of iron-sulphur-nitrosyl complexes within the tissue. This hypothesis is supported by histochemical studies which show that both clusters accumulate in endothelial cells.

Animals↗
PubMed1991

Kluyveromyces lactis toxin has an essential chitinase activity.

The Kluyveromyces lactis toxin is a protein containing three subunits (alpha, beta and gamma) which causes sensitive yeast cells to arrest proliferation in the G1 phase of the cell cycle. Despite the toxin's complex structure, the gamma subunit appears to be the only component required for it to arrest proliferation since intracellular expression of the gamma polypeptide alone in a sensitive yeast strain mimics the effect of the exogenous native toxin. The toxin alpha subunit shows sequence similarity to a variety of chitinases and here we report that the toxin is a potent exochitinase. The exochitinase activity is absolutely required for its biological activity against sensitive Saccharomyces cerevisiae cells and allosamidin, a specific inhibitor of chitinases, abolishes the biological activity of the toxin. However, since the alpha subunit is not required for the G1 arrest induced by the toxin, the chitinase activity of the toxin cannot be directly responsible for the ultimate effect of the toxin and most likely plays a role in the initial interaction of the toxin with sensitive cells.

Acetylglucosamine↗
PubMed1991

Analysis of the response of Saccharomyces cerevisiae cells to Kluyveromyces lactis toxin.

The response of Saccharomyces cerevisiae cells to the toxin produced by certain strains of Kluyveromyces lactis was studied. The toxin caused an arrest of sensitive cells in the unbudded (G1) phase of the cell cycle, consistent with the accumulation of cells with an unreplicated (G1) content of DNA in treated populations. However, toxin-treated cells were not proficient for mating. The effects of the toxin were dependent on its continuous presence for over an hour and removal of cells into fresh medium at earlier times prevented inhibition. Following toxin treatment, cells increased in volume and continued to synthesize protein and RNA, suggesting that they were able to continue growth in the absence of division. However, several lines of evidence suggested that the toxin does not simply block proliferation in G1, but that another continuous or post-G1 event is also affected. Possible models to explain these observations are discussed.

DNA Replication↗
PubMed1987

The effect of hydroxocobalamin on the nitroprusside-induced relaxation of rat aortic preparations.

Hydroxocobalamin (HOCb) when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio had no significant effect on the relaxation of noradrenaline-precontracted rat aortic rings. However, the addition of HOCb did prolong the time taken for the relaxant response to occur. The time taken for a 0.34 microM SNP dose to exert 50% of its relaxant effect was increased by about 120 and 35% with 10:1 and 1:1 HOCb/SNP molar ratio mixtures, respectively. A 0.5:1 HOCb/SNP molar ratio mixture caused no prolongation. In incubations with [14C]SNP, it was found that mixing with equimolar, or greater, amounts of HOCb, reduced aortic tissue uptake of radioactivity. The results support the hypothesis that both SNP alone and SNP/HOCb complexes breakdown extracellularly to release the same amount of active species, but that in the case of the complexes the active agent is released at a slower rate.

Animals↗
PubMed1987

Sodium nitroprusside: pharmacological aspects of its interaction with hydroxocobalamin and thiosulphate.

Hydroxocobalamin (HOCb), when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio and injected (i.v.) into the anaesthetized rat, prolonged the depressor response to SNP by 25-50%, but did not affect the degree of blood pressure lowering. Both the 'onset' and 'offset' components of the response were prolonged. Injecting [14C]SNP along with a 10-fold molar excess of HOCb resulted in a 2- to 3-fold elevation of plasma radioactivity which was maintained during the first 10 min of a 40 min experimental period. These effects of HOCb on the pharmacodynamics and pharmacokinetics of SNP are probably due to complex formation between the two compounds. Sodium thiosulphate (ST) added to SNP (12:1 molar ratio) had no effect on the depressor response to SNP. This mixing of ST and SNP had a less-marked influence on the plasma [14C] SNP-derived radioactivity than occurred with HOCb. There was no initial elevation of radioactivity, but the levels were raised by 50-60% at 4, 6 and 10 min. Since the depressor response to SNP was unaffected by ST, it is presumed that the higher concentrations of radioactivity were due to inactive degradation products rather than the active species itself.

Animals↗
PubMed1987

Further investigations regarding the toxicity of sodium nitroprusside.

Sodium nitroprusside is a valuable vasodilator, but its use has been curtailed because of numerous reports that, in the presence of blood, nitroprusside decomposes with release of toxic cyanide. We have examined the release of cyanide in terms of the known chemistry of nitroprusside and suggest that photochemical decomposition of nitroprusside and (or) its metabolism in vivo invalidates the analytical procedure used by previous workers. We also present evidence for the stability of nitroprusside in blood, based on 13C nuclear magnetic resonance studies.

Ferricyanides↗
PubMed1979

The value of routine cranial computed tomography in neurologically intact patients with primary carcinoma of the lung.

The most common cerebral metastatic lesion is from carcinoma of the lung. Preoperative cranial computed tomography (CCT) with contrast enhancement was performed in 55 neurologically intact patients with a diagnosis of bronchogenic carcinoma; 3 patients (5%) demonstrated cerebral metastasis. CCT could spare a significant number of such patients from unnecessary surgery, with a net saving substantially greater than its cost.

Brain Neoplasms↗
PubMed1979

Correlation of computed tomographic, angiographic, and neuropathological changes in giant cerebral aneurysms.

Giant aneurysms involving or adjacent to the circle of Willis exhibit three CT patterns: nonthrombotic, partially thrombotic, and completely thrombotic. Partially thrombotic aneurysms have the most specific pattern, consisting of a "target" configuration on the post-contrast scan. Ring calcification of the wall or mural thrombus is frequently observed in partially or completely thrombotic aneurysms. Calcification is not seen in nonthrombotic lesions. Angiographic and neuropathological findings are correlated with the CT findings.

Angiography↗
PubMed1979

Contrast enhanced CT scan and radionuclide brain scan in supratentorial gliomas.

The preoperative contrast enhanced CT and radionuclide brain scans of 60 patients with surgically verified supratentorial astrocytomas were evaluated and compared. Results indicated that the mechanisms of contrast enhancement and radionuclide uptake are identical in the detection of supratentorial gliomas. These diagnostic methods apparently mirror the integrity of the blood-brain barrier and therefore can be useful in assessing the degree of malignancy of supratentorial gliomas. However, lesions with an intact blood-brain barrier will be missed with radionuclide imaging. These parenchymal abnormalities and/or the associated mass effect will be detected with contrast enhanced computed tomography. These findings firmly establish contrast enhanced computed tomography. These findings firmly establish contrast enhanced CT as the primary investigate tool in the suspected brain tumor.

Adolescent↗
PubMed1978

The contrast-enhanced CT scan and the radionuclide brain scan: parallel mechanisms of action in the detection of supratentorial astrocytomas.

The preoperative contrast-enhanced CT scan and the radionuclide brain scan of 70 patients with surgically verified supratentorial astrocytomas were evaluated and compared. The results indicate parallel mechanisms of action of contrast enhancement and radionuclide uptake. These diagnostic modalities apparently mirror the integrity of the blood-brain barrier (BBB) and therefore are useful in assessing the degree of malignancy of supratentorial gliomas. However, lesions with an intact BBB will be missed with RN imaging. These lesions and/or the associated mass effect will be detected with contrast-enhanced computed tomography. Our findings firmly establish contrast-enhanced CT as the primary investigate tool in the suspected brain tumor.

Astrocytoma↗
PubMed1978

Non-contrast CT scanning: limited value in suspected brain tumor.

Most patients who have computed tomography because of a suspected brain tumor are subjected to a noncontrast scan followed by a contrast study. Analysis of the scans of all such patients over a two-year period indicates that in most cases a single contrast scan affords the same degree of diagnostic accuracy as a combined pre- and postcontrast study.

Brain Neoplasms↗
PubMed1978

Computed tomography in astrocytomas. A statistical analysis of the parameters of malignancy and the positive contrast-enhanced CT scan.

Four histopathological indices of malignancy--cellularity, pleomorphism, vascularity, and necrosis--were correlated with the positive-contrast CT scan in 84 patients with pathologically proved astrocytoma. Vascularity and necrosis correlated best with the scan in supratentorial tumors, while vascularity and cellularity correlated significantly with the scan in cerebellar astrocytomas. These findings indicate that the degree of malignancy of a supratentorial astrocytoma can be inferred from the contrast-enhanced scan, but that this is not generally possible with posterior fossa tumors.

Adolescent↗