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Biomedical subjects

A M Cameron

Publications and source records attributed to A M Cameron.

At least 37 records · Page 2Linked to original sources

Toxic exudate from the hard coral Goniopora tenuidens.

Ten colonies of Goniopora tenuidens were placed individually in sea water for 1 hr after which time the sea water was assayed using toxicity to another hard coral Galaxea fascicularis and to other colonies of G. tenuidens. Sea water from eight of the 10 colonies assayed was toxic to at least one of the bioassay organisms. Thus, G. tenuidens can extrude biologically active substances that adversely affect potential competitors, both interspecific and conspecific.

Animals↗

Widespread but variable toxicity in scleractinian corals.

Aqueous and/or aqueous ethanol extracts were made of 58 scleractinian species from 11 families, collected from Heron Island, Great Barrier Reef. At least one extract from each of 53 species (91%) exhibited activity against at least one bioassay system. Extracts from at least one colony of each of 41 species of the 58 tested were toxic to mice when injected i.p. Cytolysis of sheep red blood cells was produced by extracts from at least one colony of each of 49 species of the 57 species tested and antibacterial activity was present in extracts from at least one colony of each of 37 species of the 55 tested. Only four species from 45 species assayed yielded extracts toxic to mosquito fish. This is the first report of bioactivity in extracts of 46 species of coral and the first report of bioactivity of extracts of corals from the families Mussidae, Merulinidae, Siderastreidae, Oculinidae and Dendrophylliidae. Variable results on a particular bioassay exhibited by extracts from different colonies of a given species were analysed by the Generalized Linear Interactive Modelling system (GLIM). Toxicity to mice, cytolytic and antimicrobial activity are not significantly correlated with each other. No model could be generated to explain the variation in the incidence of cytolytic activity nor of antimicrobial activity. However antimicrobial activity varied significantly between collection trips and was negatively associated with the presence of immature gonads in the colonies. The model predicts that toxicity to mice will be higher in extracts collected when average maximum monthly air temperature is high.

Animals↗

Intracolonial variation in toxicity in scleractinian corals.

Single colonies of the scleractinian corals Lobophyllia corymbosa, Favites abdita, Favia matthaii, Favia stelligera, Platygyra daedalea, Leptoria phrygia, Cyphastrea serailia, Hydnophora exesa and Astreopora myriophthalma were permanently marked with buoys on the reef flat at Heron Island. Great Barrier Reef. Portions of colonies were removed up to seven times at intervals of two or three months. Aqueous extracts of the colony portions were assayed using six bioassay regimes namely, toxicity to mice, toxicity to a coral and a hydroid, cytolytic activity on sheep erythrocytes and sea urchin ova and for antimicrobial activity on eight bacterial species. The incidence of one type of bioactivity in an extract was not correlated with the incidence of any other type of activity in that extract. Although each coral colony provided extracts that affected at least two of the bioassay systems, different activity profiles were obtained from successive extracts of each colony. Thus there is a temporal component to the idiosyncratic nature of bioactivity within a given colony of scleractinian coral.

Animals↗

Teratogenic effects of nitrofen on cellular and functional maturation of the rat lung.

The herbicide nitrofen was administered to pregnant Sprague-Dawley and Fischer-344 rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and the effects of maturation of the perinatal lung were evaluated. Nitrofen interfered with the ontogenetic acquisition of lung cells as DNA, RNA, and protein content were subnormal. The hypoplastic lungs in the newborns were associated with structural deficits, resulting in a profound reduction of surface area available for gas exchange and depressed lung compliance. Other factors which influence pulmonary function and systemic delivery of oxygen were also considered. Adrenal catecholamines, which play an important role in surfactant production and fluid resorption in the lung during the transition to air-breathing, were markedly reduced. In addition, red blood cell concentration was significantly diminished. Taken together, these results suggest that the neonatal mortality observed in the nitrofen-treated rats is likely associated with respiratory distress caused by a number of cellular and functional aberrations. These include (a) hypoplasia and structural defects in the lung leading to deficient pulmonary function, (b) deficits in adrenal catecholamines potentially impeding the transition of the lung to air-breathing, and (c) impaired systemic delivery of oxygen due to reduced hemoglobin concentration.

Adrenal Medulla↗

Nutritional influences on adrenal chromaffin cell development: comparison with central neurons.

Neurotransmitter systems in the developing brain are generally protected from growth retardation associated with nutritional deprivation. To investigate if such protective mechanisms extend to similar tissues in the peripheral sympathetic system, maturation of the chromaffin cells of the adrenal medulla and development of their centrally derived splanchnic innervation were evaluated in rats whose nutritional status had been altered during the neonatal period by increasing (16-17 pups/litter) or decreasing (five to six pups/litter) the litter size from the standard (11-12 pups/litter). Ontogeny of adrenal catecholamine stores and activities of catecholamine-biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were monitored, along with activity of choline acetyltransferase, a marker enzyme for the preganglionic neurons innervating the chromaffin cells. Neonatal nutritional deprivation slowed body weight gain and retarded development of the chromaffin cells, as evidenced by subnormal catecholamine stores, tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities. The effects persisted despite the complete recovery of body weights postweaning. The developmental alterations were not caused by overcrowding stress, as plasma corticosterone levels were not elevated in the large litter group. Neonatal nutritional enrichment promoted body weight gain but failed to enhance development of adrenal catecholamines; tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were elevated only in the preweaning period. In contrast to effects on the chromaffin cells, altered neonatal nutritional status had only minor, transient effects on the development of the centrally derived cholinergic innervation of the adrenal and produced only small changes (less than 10%) in brain tyrosine hydroxylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Effects of suboptimal levels of extracellular calcium on the regulation of the cyclic AMP phosphodiesterase-inhibitor system and membrane differentiation in Dictyostelium discoideum.

When starved wild-type amoebae of Dictyostelium discoideum were washed and incubated in 1 mM-EGTA, their ability to induce soluble cyclic AMP phosphodiesterase (PD) activity in response to either millimolar cyclic AMP or a series of nanomolar cyclic AMP pulses was reduced by 55-75%. Supplementation of EGTA-treated cells with exogenous Ca2+ stimulated PD induction in a dose-dependent fashion (EC50 = 100-200 nM free extracellular Ca2+), and enzyme production was maximal at about 1 microM free Ca2+. Ca2+ depletion also strongly impaired production of the phosphodiesterase inhibitor (PDI). In contrast, other than delaying their appearance by about 1 h, EGTA had little effect on the induction by cyclic AMP pulses of cell surface markers such as contact sites A and membrane-bound PD activity. Similar changes in both the soluble and membrane activities were observed with strain NP368, a mutant that overproduces cyclic GMP when stimulated by cyclic AMP. Thus, Ca2+ depletion does not appear to inhibit PD and PDI production by reducing intracellular cyclic GMP. To determine whether Ca2+ depletion alters signal transduction, two mutants that produce the soluble PD activities constitutively were examined. Suboptimal concentrations of free extracellular Ca2+ were found to inhibit PD production in these cells to the same degree and with the same concentration dependence as low Ca2+ inhibited PD induction by cyclic AMP in wild-type cells. These results suggest that Ca2+ depletion by EGTA probably inhibits PD and PDI production indirectly by perturbing an intracellular Ca2+ pool(s) rather than by altering a surface cyclic AMP-receptor-mediated process.

3',5'-Cyclic-AMP Phosphodiesterases↗

Role of sympathetic neurons in biochemical and functional development of the kidney: neonatal sympathectomy with 6-hydroxydopamine.

Renal sympathetic function develops over the first 3 weeks of postnatal life in the rat. In the current study, the effects of neonatal sympathectomy with 6-hydroxydopamine were examined on renal biochemical and functional development. The completeness and persistence of sympathetic nerve loss were confirmed by direct measurement of norepinephrine levels and turnover. Evidence was obtained for adverse effects on cellular maturation, as shown by perturbations in the ornithine decarboxylase/polyamine system, which is controlled partially by beta adrenergic input and which regulates macromolecule synthesis in developing cells. A later phase of 6-hydroxydopamine-induced alterations in renal development was seen during the period in which synaptogenesis is prominent and sympathetic tone is high (end of the 2nd postnatal week to end of the 3rd week): the denervated kidneys displayed supersensitivity of beta adrenergically mediated cyclic AMP responses without changes in receptor binding. The alterations in biochemical indices of cellular maturation were accompanied by abnormalities of renal function. 6-Hydroxydopamine caused an increase in the fractional excretion of sodium and deficits in physiological responsiveness of the kidney to a vasopressin analog. Later on, alterations in glomerular filtration rate and basal urinary osmolality also were prominent. These results indicate that neonatal sympathectomy has an adverse effect on the biochemical and functional development of the kidney.

Animals↗

Neonatal central catecholaminergic lesions with intracisternal 6-hydroxydopamine: effects on development of presynaptic and postsynaptic components of peripheral sympathetic pathways and on the ornithine decarboxylase/polyamine system in heart, lung and kidney.

Peripheral sympathetic neurons are thought to provide trophic regulatory signals for development of adrenergic target tissues. In the current study, we destroyed central catecholaminergic pathways in the neonatal rat by intracisternal administration of 6-hydroxydopamine, which compromises sympathetic tone without ablating peripheral nerve terminals. Measurements of norepinephrine levels and turnover confirmed the effectiveness of the treatment in projections to heart, lung and kidney. The impairment of sympathetic tone was associated with a deficit in cardiac beta adrenergic receptor binding capabilities; in contrast, binding sites in the lung were unaffected and renal receptors were up-regulated. Similarly, intracisternal administration of 6-hydroxydopamine produced tissue-selective alterations in ornithine decarboxylase activity and levels of the polyamines. These results support the view that neural activity exerts an influence on the biochemical development of sympathetic target tissues; however, other trophic factors may derive from the presence of intact nerve terminals themselves, as distinct from activity.

Animals↗

Trophic control of lung development by sympathetic neurons: effects of neonatal sympathectomy with 6-hydroxydopamine.

The onset of peripheral sympathetic neuronal function is thought to provide trophic regulatory signals for development of adrenergic target tissues. In the current study, we examined the effects on lung development of neonatal sympathectomy with 6-hydroxydopamine. The completeness of the lesion and effectiveness in reducing sympathetic input to the tissue were confirmed by direct measurement of norepinephrine levels and turnover. Despite the denervation, no evidence of beta-receptor up-regulation was found; in fact, receptor binding sites tended to be reduced throughout development. The cyclic AMP response to isoproterenol challenge was initially suppressed in the lesioned animals, but became supersensitive even in the face of reduced receptor binding capabilities. Evidence was also obtained for ontogenetic abnormalities in the ornithine decarboxylase/polyamine system, which is partially controlled by beta-adrenergic input and which regulates macromolecule synthesis in replicating and differentiating cells. Eventually, the alterations were reflected in aberrant developmental patterns of DNA, RNA and protein in the lung. These results indicate that sympathetic neurons influence the biochemical development of the lung and may serve to program permanently the relationships among receptor sites, receptor coupling to cellular function, and control of cell maturation.

Animals↗

Effects of calcium antagonists on cyclic AMP phosphodiesterase induction in Dictyostelium discoideum.

Previous studies have suggested that cyclic GMP and/or Ca2+ might function as second messengers in the induction by exogenous cyclic AMP of the cyclic AMP phosphodiesterase (PD) in Dictyostelium discoideum. To assess further the role of Ca2+ in PD induction we examined the effect on this process of a number of putative Ca2+-channel blockers. At relatively low micromolar concentrations, TMB-8, nicardipine, nifedipine, diltiazem and verapamil all altered cell shape and inhibited PD induction in a similar dose-dependent fashion. Concentrations of these drugs that abolished PD induction had no effect on cell viability; however, higher concentrations reduced viability and caused cell lysis. All effects of these compounds on the cells were antagonized at least partially by 5-10 mM-Ca2+. Other cations tested were considerably less effective. Like the organic inhibitors, La3+ also altered cell shape, inhibited PD induction and reduced cell viability at elevated concentrations, but its effect on the cells appeared to be more complex. Inhibition of PD induction by the organic antagonists could not be attributed solely to an impaired uptake of extracellular Ca2+, a reduction of ATP pools in the cells or a direct effect on calmodulin. Concentrations of TMB-8 that inhibited PD induction had little effect on the cyclic GMP response. Therefore, this compound did not inhibit PD induction indirectly by blocking cyclic GMP synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

Effect of a smooth muscle relaxant from the stonefish, Synanceia trachynis, on KCl-induced responses in the guinea-pig vas deferens.

Stonefish skin secretion contains a smooth muscle relaxant, synancein II, that selectively inhibits tonic responses of KCl-induced contractions of the guinea-pig vas deferens. Synancein II (5-50 micrograms/ml) and nifedipine (10(-8)-10(-7) M) reduced tonic responses equally. Over these concentrations, synancein II inhibited phasic responses more than did nifedipine. Rapid inhibition of phasic responses by synancein II (low concentrations) but its inability to block this response at high concentrations suggests that more than one extracellular and/or intracellular Ca2+ source may contribute to the generation of the phasic response. Some calcium antagonists selectively inhibit tonic responses induced by KCl in many different organs, whilst others inhibit phasic responses. Whereas we previously reported that synancein II selectively inhibits phasic rather than tonic responses in the guinea-pig ileum, the present results reveals a reversal of this selectivity.

Animals↗

Characterization of revertants of stmF mutants of Dictyostelium discoideum: evidence that stmF is the structural gene of the cGMP-specific phosphodiesterase.

stmF mutants of Dictyostelium discoideum produce long, banded aggregation streams on growth plates and exhibit altered cGMP metabolism. To learn more about the role of cGMP in chemotaxis and the nature of the defect in these mutants, 15 nonstreaming (Stm+) revertants of two stmF mutants were isolated and characterized. Fourteen of the revertants continued to show the elevated cAMP-induced cGMP response and very low cGMP-specific phosphodiesterase (cGPD) activity characteristic of their stmF parents. Parasexual genetic analysis revealed that many of these Stm+ revertants carried phenotypic suppressors unlinked to stmF. One Stm+ revertant, strain HC344, exhibited a low, prolonged cGMP response and relatively high cGPD activity throughout development. To determine whether the elevated cGPD activity in this revertant resulted from increased enzyme production or enhanced enzyme activity, cGPDs were partially purified from the wild-type strain, the stmF parent and revertant HC344, and properties of the enzymes were compared. cGPDs from the stmF mutant and the revertant showed similar differences from the wild-type enzyme in kinetic properties, thermal stability, and sensitivity to certain inhibitors. These results suggest that stmF is the structural gene of the cGPD. In addition, the unusual cGMP response in revertant HC344 appeared to be due to increased production of an altered cGPD.

3',5'-Cyclic-GMP Phosphodiesterases↗

Effects of prenatal nitrofen exposure on cardiac structure and function in the rat.

The herbicide nitrofen was administered to pregnant Fischer-344 and Sprague-Dawley rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and its effects on cardiac structure and function were investigated in the offspring. In the 21-day fetuses, nitrofen did not influence intrauterine growth or basal heart rate. In contrast, the herbicide produced a marked depression of heart rate and abnormal electrocardiographic (ECG) profiles in the newborn rats, in conjunction with labored respiratory movements and a profound increase in postnatal mortality. A few animals displayed cardiac ventricular septal defects and diaphragmatic hernias but these malformations did not appear to be associated with the ECG changes. The chronotropic deficiencies seen in the nitrofen-treated pups were reversible by acute hyperoxia (40% oxygen). These results suggest that the teratogenic effects of nitrofen on cardiac physiology and on postnatal mortality cannot be accounted for solely by specific gross anatomical damages to the rat heart and diaphragm; rather, other more subtle morphological and physiological factors which contribute to improper systemic delivery and cellular utilization of oxygen may be involved.

Animals↗

A dietary survey of an isolated population in the UK: the islanders of Orkney.

Isolated communities, such as those in the Highlands and Islands of Scotland have a dietary pattern and lifestyle which may differ from the rest of the country. We have studied the diets of 118 Orkney Islanders (78 women, 40 men) over 2 non-consecutive weeks, using a semi-weighed methodology. 'High tea', soups, fish, potatoes and bakery goods were features of the traditional dietary pattern. Fresh fruit and vegetable tended to be low, and intakes of vitamin C and, to a lesser extent, dietary fibre, were low in relation to energy. Energy intakes of men were consistent with an active lifestyle, while fat provided 42 per cent of the energy from food. The implications of these findings are discussed in relation to the COMA recommendations and the prevalence of heart disease in this region of Britain.

Diet Surveys↗

Age effects on glycosylated blood proteins in lean and obese hyperglycaemic (ob/ob) mice.

Glycosylated haemoglobins and glycosylated plasma proteins were measured by affinity chromatography using Glycogel B, in 2-40 weeks old lean (+/+) and Aston obese hyperglycaemic (ob/ob) mice, and compared with changes in glucose concentrations. Lean mice showed an increase in glycaemia at weaning (3 weeks), and a small rise thereafter. In comparison with lean mice, ob/ob mice showed decreased glucose concentrations at 2 weeks, euglycaemia at 3-6 weeks, and hyperglycaemia from 7 weeks. The increases in glycaemia were followed by elevations of glycosylated haemoglobins after 1 week in ob/ob mice and 2 weeks in lean mice. Glycosylated haemoglobins were significantly elevated in ob/ob mice at 8-40 weeks. The glycosylated haemoglobins and glucose concentrations were correlated (r = +0.7; p less than 0.01; n = 96) for all mice studied. There was no correlation between glycosylated plasma proteins and glucose, or between glycosylated plasma proteins and glycosylated haemoglobins. Glycosylated plasma proteins were unchanged with age in lean mice, and were not significantly raised in ob/ob mice. The results indicate that glycosylated plasma proteins are a poor indicator of the glycaemic environment in mice due to their rapid turnover. In contrast, measurement of glycosylated haemoglobins provides a convenient and reliable assessment of blood glucose homeostasis in the preceding 1-2 weeks.

Aging↗

Circulating steroids in male rats following inhalation of n-alcohols.

The effect of inhaled methanol, ethanol, n-propanol and n-butanol on male reproductive function as measured by the serum concentration of circulating T (testosterone) and LH (luteinizing hormone) has been investigated. The animals were exposed to concentrations of these alcohols equal to the current threshold limit values in industry (methanol: 200 ppm, ethanol: 1000 ppm, n-propanol, n-butanol: 50 ppm) 6 h a day for up to 1 week. A significant depression in the concentration of circulating T was found after the first 6 h exposure to the respective alcohols with restoration after a recovery period of 18 h, except in rats exposed to n-butanol where a depression of 48% could still measured. The concentration of LH was within the normal range in all experimental groups whereas corticosterone was increased after exposure to n-butanol. Exposure for 1 week was not associated with any significant inability of the rat testis to produce T.

1-Butanol↗

Genetic locus (stmF) associated with cyclic GMP phosphodiesterase activity in Dictyostelium discoideum maps in linkage group II.

Previous attempts to map the stmF locus in Dictyostelium discoideum, by using only clone morphology as a marker, have led to equivocal results. Since strains carrying mutations at the stmF locus possess very low cyclic GMP phosphodiesterase activity, we have remapped this locus using both morphological and biochemical markers. Our results indicate that mutations producing a stable "streamer" phenotype and reduced cyclic GMP phosphodiesterase activity are located in linkage group II, probably centromere distal to acrA.

3',5'-Cyclic-GMP Phosphodiesterases↗

Circulating concentrations of testosterone, luteinizing hormone and follicle stimulating hormone in male rats after inhalation of methanol.

Male mature rats were examined for alterations in circulating free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after inhalation of methanol vapour in a dynamic system for up to 6 weeks at doses ranging 200 ppm to 10,000 ppm. The most extensive effects were observed after exposure to 200 ppm of methanol for 6 weeks with serum testosterone concentrations being 32% of the controls. A significant change in LH concentration after exposure to 10,000 ppm of methanol for 6 weeks was also demonstrated. FSH remained unchanged throughout these experiments. Such exposure did not change the elimination rate of testosterone from blood which indicated effects on the testicular synthesis of testosterone.

Air Pollutants↗