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Biomedical subjects

J B Sutherland

Publications and source records attributed to J B Sutherland.

At least 19 recordsLinked to original sources

Determination of fumonisins B1, B2, B3 and B4 by high-performance liquid chromatography with evaporative light-scattering detection.

Fumonisins B1, B2, B3 and B4 (FB1-FB4), a group of mycotoxins produced by the fungus Fusarium moniliforme, were separated by HPLC using an analytical-scale, base-deactivated C8 column and a gradient of trifluoroacetic acid buffer (pH 2.7) and acetonitrile. An evaporative light-scattering detector was used to detect the fumonisin peaks. A semi-preparative-scale, base-deactivated C8 column with a 1:14 mobile phase split facilitated the purification of analytical standards of FB.

Chromatography, High Pressure Liquid

Detoxification of polycyclic aromatic hydrocarbons by fungi.

The polycyclic aromatic hydrocarbons (PAHs) are a group of hazardous environmental pollutants, many of which are acutely toxic, mutagenic, or carcinogenic. A diverse group of fungi, including Aspergillus ochraceus, Cunninghamella elegans, Phanerochaete chrysosporium, Saccharomyces cerevisiae, and Syncephalastrum racemosum, have the ability to oxidize PAHs. The PAHs anthracene, benz[a]anthracene, benzo[a]pyrene, fluoranthene, fluorene, naphthalene, phenanthrene, and pyrene, as well as several methyl-, nitro-, and fluoro-substituted PAHs, are metabolized by one or more of these fungi. Unsubstituted PAHs are oxidized initially to arene oxides, trans-dihydrodiols, phenols, quinones, and tetralones. Phenols and trans-dihydrodiols may be further metabolized, and thus detoxified, by conjugation with sulfate, glucuronic acid, glucose, or xylose. Although dihydrodiol epoxides and other mutagenic and carcinogenic compounds have been detected as minor fungal metabolites of a few PAHs, most transformations performed by fungi reduce the mutagenicity and thus detoxify the PAHs.

Biodegradation, Environmental

Metabolism of phenanthrene by Phanerochaete chrysosporium.

The white rot fungus Phanerochaete chrysosporium metabolized phenanthrene when it was grown for 7 days at 37 degrees C in a medium containing malt extract, D-glucose, D-maltose, yeast extract, and Tween 80. After cultures were grown with [9-14C]phenanthrene, radioactive metabolites were extracted from the medium with ethyl acetate, separated by high-performance liquid chromatography, and detected by liquid scintillation counting. Metabolites from cultures grown with unlabeled phenanthrene were identified as phenanthrene trans-9,10-dihydrodiol, phenanthrene trans-3,4-dihydrodiol, 9-phenanthrol, 3-phenanthrol, 4-phenanthrol, and the novel conjugate 9-phenanthryl beta-D-glucopyranoside. Identification of the compounds was based on their UV absorption, mass, and nuclear magnetic resonance spectra. Since lignin peroxidase was not detected in the culture medium, these results suggest the involvement of monooxygenase and epoxide hydrolase activity in the initial oxidation and hydration of phenanthrene by P. chrysosporium.

Basidiomycota

Doses and population irradiation factors for Canadian radiation technologists (1978 to 1988).

Individual and collective radiation doses received by Canadian radiation technologists (RTs) working in diagnostic radiology, nuclear medicine and radiotherapy are summarized for the period 1978 to 1988. The data were obtained directly from the National Dose Registry, Department of National Health and Welfare. Over the 11-year study period the mean annual dose equivalent fluctuated around 0.2, 1.8 and 1.1 mSv for RTs working in diagnostic radiology, nuclear medicine and radiotherapy respectively. Over the same period the occupational collective dose equivalent decreased in diagnostic radiology (by 44%) and radiotherapy (by 35%) and increased in nuclear medicine (by 45%). Approximately 10,000 RTs are monitored each year, with an estimated total occupational collective dose equivalent of about 3.6 person-sieverts. Analysis of dose distribution data showed that only 1.3% of all monitored RTs received an annual whole-body dose equivalent greater than the current legal limit for members of the public (5 mSv). Approximately half of the RTs working in nuclear medicine and radiotherapy received an annual dose equivalent in excess of 0.5 mSv; only 7.3% of their diagnostic radiology counterparts exceeded this level. Demographic data showed a high preponderance of young women in all three RT classifications, and an analysis of the radiation risks to this occupational group revealed increases of up to 12% above the risk associated with a "standard" adult working population exposed to the same collective dose equivalent.

Adult

Stereoselective formation of a K-region dihydrodiol from phenanthrene by Streptomyces flavovirens.

The metabolism of phenanthrene, a polycyclic aromatic hydrocarbon (PAH), by Streptomyces flavovirens was investigated. When grown for 72 h in tryptone yeast extract broth saturated with phenanthrene, the actinomycete oxidized 21.3% of the hydrocarbon at the K-region to form trans-9,10-dihydroxy-9,10-dihydrophenanthrene (phenanthrene trans-9,10-dihydrodiol). A trace of 9-phenanthrol was also detected. Metabolites isolated by thin-layer and high performance liquid chromatography were identified by comparing chromatographic, mass spectral, and nuclear magnetic resonance properties with those of authentic compounds. Experiments using [9-14C]phenanthrene showed that the trans-9,10-dihydrodiol had 62.8% of the radioactivity found in the metabolites. Circular dichroism spectra of the phenanthrene trans-9,10-dihydrodiol indicated that the absolute configuration of the predominant enantiomer was (-)-9S,10S, the same as that of the principal enantiomer produced by mammalian enzymes. Incubation of S. flavovirens with phenanthrene is an atmosphere of 18O2, followed by gas chromatographic/mass spectral analysis of the metabolites, indicated that one atom from molecular oxygen was incorporated into each molecule of the phenanthrene trans-9,10-dihydrodiol. Cytochrome P-450 was detected in 105,000 x g supernatants prepared from cell extracts of S. flavovirens. The results show that the oxidation of phenanthrene by S. flavovirens was both regio- and stereospecific.

Biodegradation, Environmental

Three-dimensional lithographic model building from volume data sets.

Computed tomographic images of a dry human skull and an in-situ knee joint were used to construct solid three-dimensional polymer models using stereolithographic techniques that have been introduced recently into the manufacturing industry. The stereolithographic technique makes use of a computer-steered narrow laser beam to solidify the model within a bath of liquid photocurable polymer. The method does not suffer from the cutting-tool size and path constraints encountered in the more commonly used process of machining the models from a solid block of foam.

Humans

Quantification of abnormal intracranial pressure waves and isotope cisternography for diagnosis of occult communicating hydrocephalus.

Nineteen consecutive patients with suspected occult communicating hydrocephalus were investigated by means of clinical evaluation, neuropsychological testing, isotope cisternography, computed tomography scanning, and continuous intracranial pressure monitoring. Semi-quantitative grading systems were used in the evaluation of the clinical, neuropsychological, and cisternographic assessments. Clinical examination, neuropsychological testing, and computed tomography scanning were repeated 3 months after ventriculoperitoneal shunting. All patients showed abnormal intracranial pressure waves and all improved after shunting. There was close correlation between number, peak, and pulse pressures of B waves and the mean intracranial pressure. However, quantification of B waves by means of number, frequency, and amplitude did not help in predicting the degree of clinical improvement postshunting. The most sensitive predictor of favorable response to shunting was enlargement of the temporal horns on computed tomography scan. Furthermore, the size of temporal horns correlated with mean intracranial pressure. There was no correlation between abnormalities on isotope cisternography and clinical improvement.

Aged

Costs and benefits of low-osmolality contrast agents in radiology.

We have examined the costs and benefits associated with the introduction of low-osmolality contrast agents into general radiology. The result is a cost of $2,000,000 to save a life and $100,000 to save a year-of-life if it is assumed that these agents are ten times safer than conventional contrast agents in terms of fatality rates. These values are comparable to the costs of saving a life, and a year-of-life, associated with radiation protection practice, but appear to be over an order of magnitude higher than the corresponding costs in contexts such as mammography screening programs. Cost-benefit analysis provides a useful insight into medical decision making when available resources are limited. It raises the important question of whether society at large is allocating sufficient resources to health care.

Adolescent

Treatment of liver tumors with yttrium-90 microspheres alone.

Fifteen patients with liver metastases and one patient with hepatoma were treated by infusing 15 microns diameter plastic microspheres containing yttrium-90 into the hepatic artery. Twenty additional patients were screened but were found to be unsuitable for treatment. Follow-up angiography was done in 13 of the 16 treated patients. In five patients there was a reduction in tumor volume by more than 50% and in another two patients there was a smaller reduction. In six patients gastritis or gastric ulceration occurred and in three this was demonstrated to be due to unintended infusion of microspheres into the gastric circulation. For patients treated with yttrium-90 microspheres, mean survival time after referral was 62 weeks and in the untreated group it was 30 weeks, although this difference was not significant. We conclude that yttrium-90 microspheres alone can effect reduction in the size of liver tumors in some patients in whom their use is feasible.

Follow-Up Studies

Metabolism of cinnamic, p-coumaric, and ferulic acids by Streptomyces setonii.

Streptomyces setonii strain 75Vi2 was grown at 45 degrees C in liquid media containing yeast extract and trans-cinnamic acid, p-coumaric acid, ferulic acid, or vanillin. Gas chromatography, thin-layer chromatography, and mass spectrometry showed that cinnamic acid was catabolized via benzaldehyde, benzoic acid, and catechol; p-coumaric acid was catabolized via p-hydroxybenzaldehyde, p-hydroxybenzoic acid, and protocatechuic acid; ferulic acid was catabolized via vanillin, vanillic acid, and protocatechuic acid. When vanillin was used as the initial growth substrate, it was catabolized via vanillic acid, guaiacol, and catechol. The inducible ring-cleavage dioxygenases catechol 1,2-dioxygenase and protocatechuate 3,4-dioxygenase were detected with an oxygen electrode in cell-free extracts of cultures grown in media with aromatic growth substrates and yeast extract.

Cinnamates

Effect of positive end-expiratory pressure on left ventricular mechanics in patients with hypoxemic respiratory failure.

When positive end-expiratory pressure (PEEP) is added to intermittent positive pressure ventilation, cardiac output and stroke volume frequently fall despite unchanged or increased transmural left ventricular end-diastolic pressure. To determine whether a part of the fall in stroke volume with PEEP is explained by depressed left ventricular systolic function (increased end-systolic volume at a given end-systolic pressure on PEEP) the authors measured left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and the corresponding pressures in nine patients with acute hypoxemic respiratory failure. Measurements were made before and after 10 cm H2O PEEP was added to the ventilator. PEEP reduced mean stroke volume from 71 to 62 ml and this was explained entirely by a reduction in end-diastolic volume from 135 to 112 ml (P less than 0.005). Despite reduced EDV, pulmonary wedge pressure increased from 12 to 14 torr on PEEP, indicating reduced diastolic compliance or unstressed volume of the left ventricle in these patients similar to that reported in dogs. The authors conclude that PEEP reduces venous return and cardiac output without depressing left ventricular pumping function because end-systolic volume decreased from 64 to 49 ml on PEEP despite identical blood pressures (78 torr). They speculate that PEEP might improve ventricular performance by increasing intrathoracic pressure and left ventricular pressure relative to systemic blood pressure in extrathoracic vessels.

Adult

Streptomyces setonii: catabolism of vanillic acid via guaiacol and catechol.

Streptomyces setonii (strain 75Vi2) was grown at 45 degrees C in liquid media containing simple aromatic compounds as principal carbon sources. Thin-layer chromatography, UV spectrophotometry, and gas chromatography were used to show that S. setonii converted benzoic acid, guaiacol, and vanillic acid to catechol; p-hydroxybenzoic acid to protocatechuic acid; and m-hydroxybenzoic acid to gentisic acid. Presence of the ring-cleavage enzymes catechol 1,2-dioxygenase, protocatechuate 3,4-dioxygenase, and gentisate 2,3-dioxygenase was shown both by O2 uptake in ring-cleavage reactions catalyzed by cell-free extracts and by changes in UV spectra that indicated the presence of specific ring-cleavage products. A unique feature of this strain was its catabolism of vanillic acid by of guaiacol and catechol, using a pathway that had not been confirmed previously.

Benzoates

Renal transplant uptake of technetium-99m sulfur colloid in various time periods after transplantation.

The uptake of technetium-99m sulfur colloid (TSC) by transplanted kidneys undergoing rejection has been described. In this retrospective study, the value of TSC uptake in diagnosing renal rejection was studied in different time intervals after renal transplantation. Within 14 days after transplantation, increasing uptake was seen in 88% of 26 rejection episodes. In patients with acute tubular necrosis, 42% of their studies showed TSC uptake. TSC did not predict rejection within the three days prior to rejection. Sensitivity, specificity and accuracy of 128 TSC studies were compared at different thresholds of TSC uptake; at best, accuracy was only 76%. In later time intervals, a much smaller percentage of patients had increasing uptake with rejection; this tendency was to remain unchanged. Many non-rejection studies showed some TSC uptake. In chronic rejection, persistently marked uptake dominated prior to one year after transplantation, but not beyond this. Thus, within 14 days after transplantation, TSC uptake may support the diagnosis of rejection. Thereafter its value becomes greatly limited.

Evaluation Studies as Topic

Timing of distant flap pedicle division using xenon 133 clearance.

Clearance of intradermally injected xenon 133 was used to measure blood flow in distant flaps in humans with the donor pedicle temporarily clamped just prior to division. All 18 flaps with a blood flow of 0.5 ml per 100 gm of tissue per minute or more survived completely after separation. Of 7 with lesser flow, 3 underwent marginal necrosis adjacent to the line of division and 4 survived entirely. The false-negative result (complete flap survival in 4 patients) was artifactual due to isotope injection too close to the clamp, reflecting increased local tissue tension caused by the clamp rather than low blood flow in the flap. Xenon 133 washout does permit quantitative evaluation of blood flow, and since it is a clean isotope, it appears superior to sodium 24 and technetium 99m, which have been used in a similar manner. The test is proposed as an adjunct to clinical judgment in timing pedicle division.

Humans

Xenon-133 ventilation and perfusion studies in bronchiectasis.

Thirty-nine Xenon-133 ventilation and perfusion studies in 36 patients with bronchiectasis were analyzed retrospectively. These patients showed a marked reduction in ventilation with a less severe reduction in pulmonary arterial perfusion, resulting in areas of low ventilation-perfusion ratios. In those patients with bronchographic confirmation, xenon studies had greater sensitivity (0.89) than the chest radiographs (0.71). Where both the radiograph and the scan are normal, bronchiectasis is virtually excluded; therefore bronchography is not indicated.

Adolescent