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Biomedical subjects

J M Tobin

Publications and source records attributed to J M Tobin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Organotin compounds and their interactions with microorganisms.

Organotin compounds are ubiquitous in the environment. The general order of toxicity to microorganisms increases with the number and chain length of organic groups bonded to the tin atom. Tetraorganotins and inorganic tin have little toxicity. Because of their lipophilicity, organotins are regarded as membrane active. There is evidence that the site of action of organotins may be both at the cytoplasmic membrane and intracellular level. Consequently, it is not known whether cell surface adsorption or accumulation within the cell, or both is a prerequisite for toxicity. Biosorption studies on a fungus, cyanobacteria, and microalgae indicates that cell surface binding alone occurred in these organisms, while studies on the effects of TBT (tributyltin) on certain microbial enzymes indicated that in some bacteria TBT can interact with cytosolic enzymes. Microorganism-organotin interactions are influenced by environmental conditions. In aquatic systems, both pH and salinity can determine organotin speciation and therefore reactivity. These environmental factors may also alter selectivity for resistant microorganisms in polluted systems. Tin-resistant microorganisms have been identified, and resistance can be either plasmid or chromosomally mediated. In one TBT-resistant organism, an Altermonas sp., an efflux system was suggested as the resistance mechanism. Biotransformation of organotin compounds by debutylation or methylation has been observed. These reactions may influence the toxicity, mobility, and environmental fate of organotin compounds.

Bacteria↗
PubMed1998

Manganese toxicity towards Saccharomyces cerevisiae: dependence on intracellular and extracellular magnesium concentrations.

Inhibition of the growth of Saccharomyces cerevisiae was evident at concentrations of 0.5 mM Mn2+ or higher, but a tolerance to lower Mn2+ concentrations was observed. The inhibitory effects of 2.0 mM Mn2+ were eliminated by supplementing the medium with excess Mg2+ (10 mM), whereas addition of excess Ca2+ and K+ had negligible effect on Mn2+ toxicity. Growth inhibition by Mn2+, in the absence of a Mg2+ supplement, was attributed to Mn2+ accumulation to toxic intracellular levels. Mn levels in S. cerevisiae grown in Mg(2+)-supplemented medium were severalfold lower than those of cells growing in unsupplemented medium. Mn2+ toxicity was also influenced by intracellular Mg, as Mn2+ toxicity was found to be more closely correlated with the cellular Mg:Mn ratio than with cellular Mn levels alone. Cells with low intracellular levels of Mg were more susceptible to Mn2+ toxicity than cells with high cellular Mg, even when sequestered Mn2+ levels were similar. A critical Mg:Mn ratio of 2.0 was identified below which Mn2+ toxicity became acute. The results demonstrate the importance of intracellular and extracellular competitive interactions in determining the toxicity of Mn2+.

Calcium↗
PubMed1997

Manganese uptake and toxicity in magnesium-supplemented and unsupplemented Saccharomyces cerevisiae.

The magnesium content of Saccharomyces cerevisiae was found to vary by up to fivefold at differing stages of batch growth and during growth in the presence of differing magnesium concentrations. Excess Mg was primarily sequestered in vacuoles. Mn(2+)-uptake experiments revealed that Mg-enriched cells had a markedly reduced capacity for Mn2+ accumulation. For example, after 6 h incubation in the presence of 50 microM Mn2+, Mn levels were approximately twofold higher in cells previously grown in unsupplemented medium than in those from Mg-supplemented medium. These differences were further accentuated at higher Mn2+ concentrations and were not attributable to altered cell-surface charge or altered cell-surface Mn2+ binding. Cellular Mg status also influenced Mn toxicity towards S. cerevisiae. During exposure to 5 mM Mn2+, 50% reductions in the viability of cells with initial Mg contents of approximately 1400 and 2700 nmol (10(9) cells)-1 occurred after approximately 1.6 h and 3.6 h respectively. In cells containing 3300 nmol Mg (10(9) cells)-1, more than 75% viability was still maintained after 7 h incubation with 5 mM Mn2+. It is concluded that Mn2+ uptake and toxicity in S. cerevisiae are strongly influenced by intracellular Mg, possibly through Mg-dependent regulation of divalent-cation transport activity.

Ion Transport↗
PubMed1997

Posture and gastro-oesophageal reflux: a case for left lateral positioning.

AIM: Prone posture is often recommended for symptomatic gastroesophageal reflux in young infants, but prone positioning has been associated with sudden infant death. The aim of this study was thus to establish the optimal alternative posture for reducing reflux. METHODS: 24 infants (< 5 months) with symptomatic gastro-oesophageal reflux were studied prospectively with 48 h pH monitoring. They were randomly assigned to one of the 24 permutations of the four positions (supine, prone, right, left). During the first 24 hours the infant was held horizontally, and then the permutation was repeated at 30 degrees head elevation, giving a total of eight study segments for each infant. Data were edited to remove all time when the infants were not in the prescribed positions. Results were evaluated using analysis of covariance. RESULTS: Gastro-oesophageal reflux expressed as reflux index (mean % (SEM)) was significantly less in the prone and left lateral positions (6.72 (1.06) and 7.69 (1.03) respectively) than in the supine and right lateral positions (15.33 (2.33) and 12.02 (1.38); p < 0.001). Head elevation did not affect any variables significantly. CONCLUSIONS: Head elevation may not always be of clinical value. The left lateral position is a suitable alternative to prone for the postural management of infants with symptomatic gastro-oesophageal reflux.

Analysis of Variance↗
PubMed1996

Fungal melanins and their interactions with metals.

Fungal melanins are dark brown or black pigments located in cell walls. They also exist as extracellular polymers. Melanized fungi possess increased virulence and resistance to microbial attack as well as enhanced survival while under environmental stress. Melanins contain various functional groups which provide an array of multiple nonequivalent binding sites for metal ions. Pigmented Cladosporium cladosporoides was shown to biosorb 2.5- to four-fold more Ni, Cu, Zn, Cd, and Pb than albino Penicillium digitatum and at four- to six-fold higher rates. Metal desorption was significantly lower for extracellular melanin than from pigmented or albino biomass which indicated the strength of the melanin-metal bond. At equilibrium, tributyltin chloride (TBTC) concentrations of 2.5 mM, pigmented and albino Aureobasidium pullulans absorbed approximately 0.9 and 0.7 mumol TBTC mg -1 dry wt, respectively, whereas purified extracellular melanin exhibited uptake levels of approximately 22 mumol TBTC mg-1 dry wt at an equilibrium concentration of only 0.4 mM. Addition of melanin to the growth medium reduced the toxic effect of CuSO4 and TBTC due to melanin metal binding and sequestration.

Cell Wall↗
PubMed1993

Mechanism of adsorption of hard and soft metal ions to Saccharomyces cerevisiae and influence of hard and soft anions.

The applicability of the hard-and-soft principle of acids and bases in predicting metal adsorption characteristics in a biological context was investigated for metabolism-independent uptake of the metal ions Sr2+, Mn2+, Zn2+, Cu2+, Cd2+, and Tl+ by Saccharomyces cerevisiae. Metal adsorption increased with external metal concentration (5 to 50 microM), although some saturation of uptake of the harder ions examined, Sr2+, Mn2+, and Zn2+, was evident at the higher metal concentrations. Cation displacement experiments indicated that, with the exception of Tl+, relative covalent bonding (H+ displacement) of the metals was greater at low metal concentrations, while weaker electrostatic interactions (Mg2+ plus Ca2+ displacement) became increasingly important at higher concentrations. These results were correlated with curved Scatchard and reciprocal Langmuir plots of metal uptake data. Saturation of covalent binding sites was most marked for the hard metals, and consequently, although no relationship between metal hardness and ionic/covalent bonding ratios was evident at 10 microM metal, at 50 microM the ratio was generally higher for harder metals. Increasing inhibition of metal uptake at increasing external anion concentrations was partially attributed to the formation of metal-anion complexes. Inhibitory effects of the hard anion SO42(-) were most marked for uptake of the hard metals Sr2+ and Mn2+, whereas greater relative effects on adsorption of the softer cations Cu2+ and Cd2+ were correlated with complexation by the soft anion S2O32(-). Inhibition of uptake of the borderline metal Zn2+ by SO42(-) and that by S2O32(-) were approximately equal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1992

Mechanisms of strontium uptake by laboratory and brewing strains of Saccharomyces cerevisiae.

Laboratory and brewing strains of Saccharomyces cerevisiae were compared for metabolism-independent and -dependent Sr2+ uptake. Cell surface adsorption of Sr2+ to live cells was greater in the brewing than in the laboratory strain examined. However, uptake levels were greater in denatured (dried and ground) S. cerevisiae, and the relative affinities of Sr2+ for the two strains were reversed. Results for the brewing S. cerevisiae strain were similar whether the organism was obtained fresh from brewery waste or after culturing under the same conditions as for the laboratory strain. Reciprocal Langmuir plots of uptake data for live biomass were not linear, whereas those for denatured biomass were. The more complex Sr2+ binding mechanism inferred for live S. cerevisiae was underlined by cation displacement experiments. Sr2+ adsorption to live cells resulted in release of Mg2+, Ca2+, and H+, suggesting a combination of ionic and covalent bonding of Sr2+. In contrast, Mg2+ was the predominant exchangeable cation on denatured biomass, indicating primarily electrostatic attraction of Sr2+. Incubation of live S. cerevisiae in the presence of glucose resulted in a stimulation of Sr2+ uptake. Cell fractionation revealed that this increased Sr2+ uptake was mostly due to sequestration of Sr2+ in the vacuole, although a small increase in cytoplasmic Sr2+ was also evident. No stimulation or inhibition of active H+ efflux resulted from metabolism-dependent Sr2+ accumulation. However, a decline in cytoplasmic, and particularly vacuolar, Mg2+, in comparison with that of cells incubated with Sr2+ in the absence of glucose, was apparent. This was most marked for the laboratory S. cerevisiae strain, which contained higher Mg2+ levels than the brewing strain.

Biological Transport, Active↗
PubMed1992

Treatment of vaginal candidosis: a comparative study of the efficacy and acceptability of itraconazole and clotrimazole.

OBJECTIVE: To compare the clinical and mycological efficacy and patient acceptability of the oral antifungal itraconazole with vaginal clotrimazole in the treatment of vaginal candidosis. DESIGN: A multicentre, single-blind, randomised, parallel group comparison of itraconazole and clotrimazole. SETTING: 17 Genito Urinary Medicine clinics in UK hospitals. SUBJECTS: Women with symptomatic, culture positive vaginal candidosis. METHODS: Patients were randomly allocated 2 x 100 mg itraconazole capsules to be taken twice in a 24 hour period, or a 500 mg clotrimazole vaginal tablet. Clinical and mycological assessments were made at entry and after approximately seven and 35 days. OUTCOME MEASURES: Cure rate was defined in terms of mycological results, and patients were questioned on their opinion of treatment. RESULTS: Of 214 patients, 109 received itraconazole and 105 clotrimazole with similar improvement in clinical signs and symptoms. Mycological cure rates one week after treatment were obtained in 72 of 97 patients (74%) in the itraconazole group and 64 of 89 patients (72%) in the clotrimazole group. Identical mycological cure rates six weeks after treatment were obtained with 40 of 79 patients (51%) receiving itraconazole and 39 of 78 patients (50%) receiving clotrimazole. CONCLUSION: Clotrimazole and itraconazole were found to be equally effective. A majority of patients receiving the latter preferred it to previous treatments.

Adult↗
PubMed1990

Effect of blood upon the selective ablation of atherosclerotic plaque with a pulsed dye laser.

Laser angioplasty systems with laser energy preferentially absorbed by atherosclerotic plaque may offer a safe method of plaque removal. This study evaluated the effect of blood upon selective energy absorption using a pulsed dye laser at 480 nm. Intra-arterial laser irradiation of normal rabbit femoral arteries demonstrated a perforation threshold energy with blood perfusion of 13.1 mJ per pulse compared to 87.9 mJ with saline (P less than .0001), indicating a deleterious effect in the presence of blood. An adverse effect upon arterial healing at 3 days was noted in sheep following intra-arterial irradiation during blood but not saline perfusion. Normal and atherosclerotic human aorta ablation thresholds differed significantly (P less than .0002) under saline (plaque: 20 mJ and normal: 120 mJ) but the difference under blood (plaque: 5 mJ and normal: 20 mJ) was not significant. We conclude that absorption of laser energy by blood can reduce the effect of differential absorption by endogenous chromophores in normal and pathologic vascular tissues and, therefore, removal of blood may be a prerequisite for selective ablation of atherosclerotic plaques.

Animals↗
PubMed1988

Recurrent vaginal candidosis: prospective study of effectiveness of maintenance miconazole treatment.

In a prospective study, 100 women with recurrent vaginal candidosis were treated with miconazole, using two 100 mg vaginal pessaries a day for one week, then one pessary twice a week for three months followed by one pessary a week for a further three months. Fifty four women elected to continue using one pessary a week for longer than six months. Symptomatic vaginal candidosis did not occur in any patient during regular maintenance treatment. Of the 46 women who discontinued treatment before six months, however, 22 had a recurrence. Maintenance prophylactic treatment with miconazole pessaries appears to be an acceptable and effective method of preventing recurrent episodes of vaginal candidosis.

Adolescent↗
PubMed1985

Are we failing our teenagers? Value of a family planning service for teenagers within the sexually transmitted disease clinic.

Out of 100 teenage girls attending a sexually transmitted disease clinic for the first time, 77 were found to be using a reliable method of contraception and had similar characteristics to teenage girls attending a family planning clinic. The 23 girls not using any reliable contraception exhibited a different pattern of sexual behaviour and were at high risk of unplanned pregnancy. Subsequently, another group of 23 girls not using contraception when seen at the sexually transmitted disease clinic were actively encouraged to attend a family planning clinic. Their risk of unplanned pregnancy was much reduced, although their pattern of sexual activity was unchanged. Ready availability of contraceptive advice for unprotected teenagers in sexually transmitted disease clinics would reduce their high risk of unplanned pregnancy.

Adolescent↗
PubMed1984

Uptake of Metal Ions by Rhizopus arrhizus Biomass.

Rhizopus arrhizus biomass was found to absorb a variety of different metal cations and anions but did not absorb alkali metal ions. The amount of uptake of the cations was directly related to ionic radii of La, Mn, Cu, Zn, Cd, Ba, Hg, Pb, UO(2), and Ag. The uptake of all the cations is consistent with absorption of the metals by sites in the biomass containing phosphate, carboxylate, and other functional groups. The uptake of the molybdate and vanadate anions was strongly pH dependent, and it is proposed that the uptake mechanism involves electrostatic attraction to positively charged functional groups.

Journal Article↗
PubMedDate not supplied

Metal cation uptake by yeast: a review.

This review addresses metal uptake specifically by yeast. Metal uptake may be passive, active or both, depending on the viability of the biomass, and is influenced by a number of environmental and experimental factors. Uptake is typically accompanied by a degree of ion exchange and, under certain conditions, may be enhanced by the addition of an energy source. Intracellularly accumulated metal is most readily associated with the cell wall and vacuole but may also be bound by other cellular organelles and biomolecules. The intrinsic biochemical, structural and genetic properties of the yeast cell along with environmental conditions are crucial for its survival when exposed to toxic metals. Conditions of pH, temperature and the presence of additional ions, amongst others, have varying effects on the metal uptake process. We conclude that yeasts have contributed significantly to our understanding of the metal uptake process and suggest directions for future work.

Hydrogen-Ion Concentration↗