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Biomedical subjects

J B Sutherland

Publications and source records attributed to J B Sutherland.

At least 37 records · Page 2Linked to original sources
PubMed1996

Fungal biotransformation of the antihistamine azatadine by Cunninghamella elegans.

The metabolism of the antihistamine azatadine by the zygomycete fungus Cunninghamella elegans ATCC 9245 was investigated. Within 72 h from the addition of the drug to 48-h-old cultures grown in Sabouraud dextrose broth, 95% of azatadine was biotransformed. Two major metabolites, 7-hydroxyazatadine (25%) and 8-hydroxyazatadine (50%), and two minor metabolites, N-desmethylazatadine and 9-hydroxyazatadine, were isolated by high-performance liquid chromatography and characterized by mass spectrometric and proton nuclear magnetic resonance spectroscopic analyses.

Biotransformation↗
PubMed1995

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↗
PubMed1993

Enantiomeric Composition of the trans-Dihydrodiols Produced from Phenanthrene by Fungi.

The trans-dihydrodiols produced during the metabolism of phenanthrene by Cunninghamella elegans, Syncephalastrum racemosum, and Phanerochaete chrysosporium were purified by high-performance liquid chromatography (HPLC). The enantiomeric compositions and optical purities of the trans-dihydrodiols were determined to compare interspecific differences in the regio- and stereoselectivity of the fungal enzymes. Circular dichroism spectra of the trans-dihydrodiols were obtained, and the enantiomeric composition of each preparation was analyzed by HPLC with a chiral stationary-phase column. The phenanthrene trans-1,2-dihydrodiol produced by C. elegans was a mixture of the 1R,2R and 1S,2S enantiomers in variable proportions. The phenanthrene trans-3,4-dihydrodiol produced by P. chrysosporium was the optically pure 3R,4R enantiomer, but that produced by S. racemosum was a 68:32 mixture of the 3R,4R and 3S,4S enantiomers. The phenanthrene trans-9,10-dihydrodiol produced by P. chrysosporium was predominantly the 9S,10S enantiomer, but those produced by C. elegans and S. racemosum were predominantly the 9R,10R enantiomer. The results indicate that although different fungi may exhibit similar regioselectivity, there still may be differences in stereoselectivity that depend on the species and the cultural conditions.

Journal Article↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

Occupational doses to medical radiation technologists in Manitoba (1978-1988).

In Canada, occupational exposure to medical technologists accounts for about 8 per cent of all occupational exposure. In this paper, occupational doses to Manitoban radiation technologists (RTs) in diagnostic radiology, nuclear medicine and radiotherapy are presented for the period 1978-1988. Particular attention is paid to the distribution of dose among this population. The importance of age and sex demographics on radiation detriment is also estimated.

Data Collection↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

Phenolic Compound Utilization by the Soft Rot Fungus Lecythophora hoffmannii.

Nine phenolic compounds were metabolized by the soft rot fungus Lecythophora hoffmannii via protocatechuic acid and subsequently cleaved by protocatechuate 3,4-dioxygenase as determined by oxygen uptake, substrate depletion, and ring cleavage analysis. Catechol was metabolized by catechol 1,2-dioxygenase. Fungal utilization of these aromatic compounds may be important in the metabolism of wood decay products.

Journal Article↗
PubMed1986

Demethylation of Veratrole by Cytochrome P-450 in Streptomyces setonii.

The actinomycete Streptomyces setonii 75Vi2 demethylates vanillic acid and guaiacol to protocatechuic acid and catechol, respectively, and then metabolizes the products by the beta-ketoadipate pathway. UV spectroscopy showed that this strain could also metabolize veratrole (1,2-dimethoxybenzene). When grown in veratrole-containing media supplemented with 2,2'-dipyridyl to inhibit cleavage of the aromatic ring, S. setonii accumulated catechol, which was detected by both liquid chromatography and gas chromatography. Reduced cell extracts from veratrole-grown cultures, but not sodium succinate-grown cultures, produced a carbon monoxide difference spectrum with a peak at 450 nm that indicated the presence of soluble cytochrome P-450. Addition of veratrole or guaiacol to oxidized cell extracts from veratrole-grown cultures produced difference spectra that indicated that these compounds were substrates for cytochrome P-450. My results suggest that S. setonii produces a cytochrome P-450 that is involved in the demethylation of veratrole and guaiacol to catechol, which is then catabolized by the beta-ketoadipate pathway.

Journal Article↗
PubMed1983

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↗
PubMed1981

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↗