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Biomedical subjects

N J Russell

Publications and source records attributed to N J Russell.

At least 73 records · Page 4Linked to original sources

Temporal and geographical distributions of epilithic sodium dodecyl sulfate-degrading bacteria in a polluted South Wales river.

Epilithic bacteria were isolated nonselectively from riverbed stones and examined by gel zymography for their ability to produce alkylsulfatase (AS) enzymes and thus to metabolize alkyl sulfate surfactants such as sodium dodecyl sulfate. The percentages of AS+ isolates from stone epilithon at five sites from the source to the river mouth were measured on five sampling days spread over 1 year. The results showed that (i) the prevalence of epilithic AS+ strains (as a percentage of all isolates) was much higher at polluted sites than at the source; (ii) when averaged over the whole river, percentages of AS+ strains were significantly higher at the end of summer compared with either the preceding or the following winter; (iii) analysis of site-sampling time interactions indicated that water quality factors (e.g., biochemical oxygen demand and dissolved oxygen concentration) rather than climatic factors determined the distributions of epilithic AS+ isolates; (iv) constitutive strains were the most prevalent (7.2% of all isolates), with smaller numbers of isolates with inducible (4.5%) and repressible (1.7%) enzymes.

Analysis of Variance↗

The role of chest radiography in patients presenting with anterior chest pain to the Accident & Emergency Department.

The chest radiological findings and outcomes of 120 consecutive patients attending the Accident & Emergency Department with anterior chest pain were recorded prospectively to investigate the value of routine chest radiography in their management. Twenty-one patients (17.5%) were excluded because of incomplete information. Thirty-seven radiological abnormalities were identified in 33 (33%) of the remaining 99 chest X-rays. Seventeen of the abnormalities identified in 14 (14%) of the chest X-rays were clinically significant. The casualty officer's interpretation of 70 (70%) of the chest X-rays was correct, but 36 errors were made interpreting the other 29 chest X-rays. Of these errors, 19 were false negative errors, resulting in the mismanagement of two patients and 17 false positive errors, resulting in the mismanagement of four patients. It appears that a routine chest X-ray provides little information of practical value in the management of patients with anterior chest pain attending an Accident & Emergency Department, unless the training of medical students and junior doctors in the interpretation of chest X-rays is improved.

Chest Pain↗

Radiolabelling patterns in alginate of Pseudomonas aeruginosa synthesized from specifically-labelled 14C-monosaccharide precursors.

Incorporations of radioactivity in alginate from specifically-radiolabelled glucose molecules by a parental strain and a gluconate-negative mutant of Pseudomonas aeruginosa were compared. The gluconate-negative mutant, which was deficient in the Entner Doudoroff pathway enzymes, produced less alginate than did the parental strain. The ratio of incorporation of radiolabel from [6-14C] versus [1-14C] glucose was 9.7:1 in the parental strain, implying that the carbon skeleton is catabolised via the Entner Doudoroff pathway. In comparison, a ratio of 1.5:1 was obtained for the mutant. Analysis of the alginate produced after growth on [6-14C] glucose showed that in both strains less radiolabel was present in carbon-6 of the constituent uronic acids than would be predicted (parental strain 8.4% and mutant 38.3% of the expected values). These results imply that TCA cycle intermediates are probably the major precursors of alginate in P. aeruginosa.

Alginates↗

Opiates inhibit the discharges of fine afferent units from inflamed knee joint of the cat.

The spontaneous discharges in 15 out of 19 small-diameter afferent units from inflamed knee joints of anaesthetized cats were significantly inhibited by one or several opiates (morphine in the dose range 1.0-5.0 mg/kg; gly-ol 0.5-5.0 mg/kg; U50488 1.0-10.0 mg/kg; ethylketocyclazacine 0.5-4.0 mg/kg administered by close arterial injection into the joint). In the majority of cases a subsequent injection of naloxone (1 mg/kg i.a.) significantly reversed this effect. These data provide an electrophysiological demonstration that opiates may act on opiate receptors located at peripheral sites of primary afferent fibres and hence exert a peripheral 'analgesic' effect.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Pharmacokinetics of kanamycin in the bullfrog, Rana catesbeiana.

1. Kanamycin disposition was studied in bullfrogs (Rana catesbeiana) following single doses IP. Both plasma t1/2 and Vd of the drug increased with increasing time after drug indicating redistribution and tight binding of kanamycin to deep tissue compartments. 2. Kanamycin was eliminated unchanged with a t1/2 plasma = 27 hr; perilymph = 89 hr; endolymph = 183 hr; aqueous humor = 54 hr; and CSF = 58 hr. 3. Kanamycin was absorbed by frogs from environmental water. 4. Environmental conditions must be carefully specified and monitored, as well as the physiological state of the animals when studying the effects of drugs on Amphibia.

Animals↗

The lipid composition and permeability to azole of an azole- and polyene-resistant mutant of Candida albicans.

Candida albicans 6.4, which is resistant to both polyene and azole groups of antifungal antibiotics, has a larger lipid content and lower polar lipid to neutral lipid ratio compared with other strains that are sensitive or resistant only to azoles. C. albicans 6.4 contains a relatively greater proportion of triacylglycerol in its neutral lipid in the exponential phase of batch culture compared with other strains, but, unlike them, does not accumulate triacylglycerols or any other stored lipid in the stationary phase. Like other strains, in C. albicans 6.4 the major phospholipids are phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, but sphingomyelin is absent; the major fatty acids are palmitic, palmitoleic, oleic and linoleic acids. In common with other C. albicans strains, strain 6.4 contains non-specific (lyso)phospholipase activity. The main distinctive feature of the lipid composition of C. albicans 6.4 is the absence of ergosterol, which is replaced by methylated sterol; mainly lanosterol, 24-methylene-24,25-dihydrolanosterol and 4-methylergostadiene-3-ol. It is suggested that the altered membrane sterol pattern provides a common basis for the double resistance by preventing polyene binding and reducing azole permeability.

Antifungal Agents↗

The role of osmotic effects in haloadaptation of Vibrio costicola.

Growth rates of Vibrio costicola showed a broad optimum between 0.8 and 1.5 M-NaCl, and there was no growth above 3.3 M-NaCl in a peptone-based medium. The minimum requirement of 0.5 M-NaCl for growth in NaCl alone was reduced to 0.3 M-NaCl when the total solute concentration was raised to 0.5 to 1.0 M equivalent with sucrose or glycerol. Compared with equivalent NaCl concentrations, higher concentrations of sucrose were more inhibitory to growth, whereas glycerol had less effect. Increasing the medium NaCl concentration suddenly by 2- or 3-fold with either a constant starting, or final, salt concentration showed that, after the shift-up, the lag in growth, the rate of growth, and the inhibition of phospholipid synthesis depended both on the final NaCl concentration and the magnitude of the shift in salinity. The time-courses of phospholipid synthesis following a 2- or 3-fold shift-up in NaCl or sucrose media were very similar and exhibited a relative increase in phosphatidylglycerol synthesis over that of phosphatidylethanolamine. This 'switch-over' was not seen following shift-up in glycerol media when there was also a stimulation, rather than inhibition, of phospholipid synthesis. It is concluded that during phenotypic haloadaptation of V. costicola, osmotic effects play a significant part in the sensing of and response to raised external salinity.

Glycerol↗

Significance of tomographic signs in the diagnosis of bronchial carcinoma.

In a previous study the value of conventional tomography was assessed in the diagnosis of 100 potentially malignant opacities on the chest radiograph. To determine which of the radiological signs were most useful the radiologists reviewed 82 of the original 100 radiographs independently, searching for the presence or absence of 36 signs. The five commonest signs of bronchial carcinoma were a mass, coarse linear shadows contiguous to a mass, unilateral hilar enlargement, linear shadows from mass to periphery, and an irregular margin to a mass. The combination of either two or three of these signs was highly sensitive, 95% and 89% respectively, in detecting carcinoma. The most useful specific signs were lobulation of the mass and cavitation with thick or irregular walls.

Bronchography↗

Sterols in Candida albicans mutants resistant to polyene or azole antifungals, and of a double mutant C. albicans 6.4.

Investigations of resistant mutants could help resolve differences and similarities in the action of azole and polyene antifungals whose modes of action are related; both disrupt membrane properties, such as permeability, by interfering with membrane sterols--polyenes by direct binding and azoles by inhibiting their synthesis. Studies of laboratory-derived mutants of Candida albicans which have an altered sterol content and/or an altered sterol composition do not provide evidence for a unified mechanism of polyene resistance. Clinical isolates of azole-resistant C. albicans have an increased or unaltered content of ergosterol and are impermeable to azoles. C. albicans 6.4, a laboratory-derived mutant resistant to both polyenes and azoles, is impermeable to azoles and has an increased content of methylated sterols. This unusual sterol composition resembles that of sensitive strains grown in the presence of azoles and may prevent polyene binding.

Antifungal Agents↗

Inhibition of 14 alpha-sterol demethylase activity in Candida albicans Darlington does not correlate with resistance to azole.

The 14 alpha-sterol demethylase in the azole-resistant Candida albicans, strain Darlington, is less sensitive to the triazole ICI 153066 than are two azole-sensitive strains, A and B. However, there is no direct correlation between the IC50 values for triazole inhibition of the demethylase and IC50 values for growth. It appears that the basis of azole resistance in strain Darlington may not be explained solely on the basis of a lack of sensitivity of its 14 alpha-sterol demethylase enzyme, but that other target sites for azole may be altered or absent.

Antifungal Agents↗

Metabolite production during the biodegradation of the surfactant sodium dodecyltriethoxy sulphate under mixed-culture die-away conditions.

Sodium dodecyltriethoxy sulphate (SDTES), either pure or as a component of commercial surfactant mixtures, underwent rapid primary biodegradation by mixed bacterial cultures in OECD screen and river-water die-away tests. Inoculation of [35S]SDTES-containing solutions with OECD screen test media acclimatized to surfactants or their degradation products led to production of various 35S-labelled glycol sulphates and their oxidation products, all known to occur during degradation of [35S]SDTES by pure bacterial isolates. Triethylene glycol monosulphate was the major catabolite together with smaller amounts of di- and monoethylene glycol monosulphates implying, by analogy with pure cultures, that ether-cleavage was the major primary biodegradation step. The oxidation product (carboxylate derivative) of each glycol sulphate was also detected together with metabolites tentatively identified as omega-/beta-oxidation products of the dodecyl chain. Relatively little SO2-4 was liberated directly from SDTES but mixed cultures derived from sewage could metabolize the sulphated glycols to SO2-4. The environmental relevance of these degradation routes was established by following metabolite production from [35S]SDTES in full-scale river-water die-away tests. Triethylene glycol sulphate was formed first, then rapidly oxidized to acetic acid 2-(diethoxy sulphate) which persisted as the major metabolite for 2-3 weeks. Small amounts of sulphated derivatives of di- and monoethylene glycols were also detected during the same period. Very little SO2-4 was formed directly from SDTES but large amounts accompanied the eventual disappearance of glycol sulphate derivatives. None of the 35S-labelled organic metabolites was persistent and, whenever [35S]SDTES was a component of a commercial mixture, all ester sulphate was completely mineralized to 35SO4(2-) within 28 d.

Biodegradation, Environmental↗

The lipid composition of azole-sensitive and azole-resistant strains of Candida albicans.

The lipid compositions of two azole-sensitive (A and B2630) and two azole-resistant (AD and KB) strains of the opportunistic fungal pathogen Candida albicans were studied by using several lipid extraction procedures: no differences were observed between the lipid content or total phospholipid/neutral lipid ratios of the four strains. All contained phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylserine as major phospholipids, with smaller amounts of phosphatidylglycerol and diphosphatidylglycerol; the relative proportions of these lipids differed between all four strains. The fatty acid composition of each major phospholipid within each strain differed, and there were also interstrain differences. A marked effect of culture growth phase in batch culture on lipid composition was observed. The major neutral lipids in each strain were triacylglycerol, non-esterified sterol and non-esterified fatty acid. The fatty acid compositions of the three fatty-acid-containing neutral lipids were distinct from each other and the phospholipids, and there were also interstrain differences. All strains possessed (lyso)phospholipase activity, which was non-specific. The proportions of triacylglycerol and non-esterified fatty acid did not vary between strains, but the azole-resistant strains AD and KB contained more non-esterified sterol, giving them a phospholipid/sterol ratio approximately half that of azole-sensitive strains. There appeared to be a relationship between the phospholipid/sterol ratio of exponentially growing sensitive strains and their ability to take up azole; this did not extend to the resistant strains, which either did not take up azole (AD and KB) or took it up at a faster rate (Darlington) than sensitive strains.

Candida albicans↗

Extravasation in the knee induced by antidromic stimulation of articular C fibre afferents of the anaesthetized cat.

Electrical stimulation of the cut distal end of the posterior articular nerve (p.a.n.) of the cat knee joint resulted in significant extravasation of plasma proteins and erythrocytes into the synovial cavity of the knee. This effect was mediated by group IV afferents (C fibres) since stimulation of p.a.n. suprathreshold for group II or III afferents but subthreshold for group IV afferents did not produce extravasation. Unmyelinated sympathetic efferent fibres in the joint nerve did not contribute to the extravasation and were responsible for a diminution of this response as shown by the enhanced extravasation occurring after adrenergic blockade. Plasma and erythrocyte extravasation was mediated by afferents containing substance P (SP), as demonstrated by the reversible abolition of extravasation when the substance P antagonist (D-Pro4,D-Trp7,9,10)-SP (4-11) was injected into the synovial cavity. In some animals it was observed that electrical stimulation of the cut distal end of p.a.n. in one limb resulted in extravasation in the contralateral knee joint. It is suggested that articular C fibre afferents could make a significant neurogenic contribution to the initiation or maintenance of inflammatory joint disease.

Anesthesia, General↗

Quantitative assessment of the value of spirometry.

To determine the value of simple spirometric measurements in the diagnostic assessment of breathless patients, doctors requesting such tests were asked to predict the likely ventilatory abnormality, expressing these pretest predictions as probabilities. Comparison of these pretest predictions with the test results allowed an analysis of the doctors' ability to identify lung function abnormalities and an assessment of the diagnostic usefulness of the test. Predictions and spirometric measurements were made in 123 patients. Doctors expressed preference for a particular spirometric category in 112 cases, of which 13 were predicted to have a restrictive defect, 77 were predicted to have an obstructive defect, and 22 were predicted to be normal. Spirometry showed that nine patients had a restrictive defect, 79 had an obstructive defect, and 24 had normal indices. The study showed that 61% of the tests gave a result that doctors predicted as being unlikely. The study also showed that doctors had difficulty in identifying the reversibility of airflow obstruction in patients in whom they correctly predicted obstruction. Spirometry fulfils a useful role in the diagnosis of breathless patients.

Adolescent↗

Lipid biosynthesis in synchronized cultures of the photosynthetic bacterium Rhodopseudomonas sphaeroides.

Lipid biosynthesis has been studied in photosynthetic cultures of Rhodopseudomonas sphaeroides that had been synchronized by stationary-phase cycling or by a centrifugation selection procedure. Synchrony index values in the range 0.70-0.80 were obtained for the first cell cycle with both synchronization methods. The major membrane lipids phosphatidylethanolamine and phosphatidylglycerol were accumulated discontinuously during the cell cycle, their mass doubling immediately before cell division. This accumulation of lipid corresponded to peaks in incorporation of radioactivity from either [1-14C]acetate or [2-3H]glycerol into individual acyl lipids as measured in individual portions of bacteria. For phosphatidylglycerol an additional peak of incorporation of radioactivity from [2-3H]glycerol was found midway through the cell cycle. In spite of their rather similar endogenous fatty acid compositions, the individual phosphoacylglycerols showed distinctive patterns of incorporation of radioactivity from [1-14C]acetate into their acyl moieties. The discontinuous synthesis of acyl lipids observed in cultures of Rhodopseudomonas sphaeroides synchronized by either stationary-phase cycling or centrifugation selection procedures contrasted with the accumulation of chlorophyll-protein complexes whose amounts were found to increase throughout the cell cycle. The implications of these findings for the control of lipid synthesis in bacterial photosynthetic membranes are discussed.

Acetates↗

Plasma extravasation in the cat knee-joint induced by antidromic articular nerve stimulation.

Antidromic electrical stimulation of C fibres in the cat knee-joint resulted in significant plasma extravasation into the synovial cavity in six out of seven cats. Preliminary findings suggest that this effect is mediated by Substance P. It is concluded that joint C fibre afferents could provide a neurogenic mechanism contributing towards the initiation or maintenance of inflammatory joint disease.

Animals↗

Effects of small-particle aerosols of local anaesthetic on dyspnoea in patients with respiratory disease.

This study was devised to test the hypothesis that dyspnoea could be mediated by unmyelinated vagal sensory nerve endings (type J receptors) situated at alveolar level in the lung. A modified jet nebulizer was used to generate an aerosol of local anaesthetic in particles small enough to allow alveolar deposition. Lignocaine (2% and 5%) produced aerosols with an arithmetic mean diameter (+/- SD) of 1.5 +/- 0.3 and 1.2 +/- 0.6 micron respectively, the mass median diameters being 1.7 (geometric standard deviation = 1.2) and 2.5 (geometric standard deviation = 1.7) micron respectively. In experimental animal models a vagally mediated tachypnoea may be induced acutely by pulmonary microembolism. This response is known to be mediated by unmyelinated pulmonary afferent nerves in the vagus. Local anaesthetic agents administered as small particles, but not as large particles, obtunded this response, which suggests that the aerosol was capable of penetration to alveolar level. Upon this background, a clinical study was designed to compare the effects of lignocaine with placebo both given as small-particle aerosols. Six patients, including two with diffuse alveolar pathology and four with chronic airflow obstruction, were studied. Respiratory frequency was determined before and after the aerosol, and exercise tolerance and breathlessness were measured with a 6 min walking test and visual analogue scales. After lignocaine there was no clinical evidence of anaesthesia of the upper airways but bronchoconstriction occurred. While no overall effect of lignocaine on dyspnoea was apparent, individual patients showed some evidence of benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗