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Biomedical subjects

R Poulin

Publications and source records attributed to R Poulin.

At least 109 records · Page 6Linked to original sources
PubMed1996

Helminth growth in vertebrate hosts: does host sex matter?

Helminth infections are usually more severe in male than in female vertebrate hosts. If parasite establishment is easier in male hosts, parasite growth may also be facilitated in males. This was tested with a meta-analysis of published between growth rates of worms in male and female vertebrate hosts. Two-thirds of the 48 comparisons found showed higher growth in male hosts than in females, but the average relative difference did not differ from zero. However, after controlling for sample size and for the variability in the original data, a small but significant effect of host sex was found. The meta-analysis suggests that male hosts harbour not only more helminths than females, but also slightly larger ones.

Animals↗
PubMed1996

Permissive role of polyamines in the cooperative action of estrogens and insulin or insulin-like growth factor I on human breast cancer cell growth.

Polyamines have been proposed as specific mediators of estrogen action in breast cancer cells, but their exact role in this process is still controversial. As estrogens cooperatively interact with peptide growth factors in several hormonal responses, the involvement of polyamines in the synergistic effect of 17 beta-estradiol (E2) and insulin or insulin-like-growth factor I (IGF-I) on cell growth, polyamine pools, specific gene induction, and cell cycle progression was examined in estrogen-responsive MCF-7 and ZR-75-1 human breast cancer cells. Spermidine depletion induced by the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), resulted in complete cytostasis and loss of mitogenic response to either E2 or insulin (or IGF-I). In contrast, a steroidal antiestrogen blocked the mitogenic effect of E2, but only partly interfered with the synergistic stimulation of estrogen action by insulin. Whereas antiestrogen-resistant growth in insulin-treated cells was halted by DFMO, the antiestrogen did not further inhibit growth upon prior polyamine depletion. E2 and either IGF-I or insulin induced early increases in putrescine and spermidine, but not spermine, contents in both MCF-7 and ZR-75-1 cells. Moreover, spermidine depletion and decarboxylated S-adenosylmethionine accumulation induced by DFMO required prior mitogenic stimulation by E2 and/or IGF-I. The antiestrogen alone had only a limited effect on polyamine and nucleoside pools. DFMO did not interfere with the coordinate induction of the estrogen- and growth factor-inducible pS2 messenger ribonucleic acid by E2 and insulin even after a 5-day treatment with the drug. On the other hand, DFMO depressed the cycling fraction of E2/IGF-I-stimulated MCF-7 cell population far more dramatically than the antiestrogen and to less than that noted in mitogen-deprived cells. However, in ZR-75-1 cells, which have a much lower spermidine/spermine ratio than MCF-7 cells, specific inhibition of spermine synthase selectively antagonized the effect of E2 compared with that of insulin. These data indicate that spermidine has a permissive role for macromolecular synthesis and cell cycle traverse, but does not qualify as a limiting factor in estrogen receptor-mediated events per se in breast cancer cells. Moreover, polyamine depletion is an efficient complementary strategy to block the mitogenic action of peptide growth factors, which is only partly antagonized by antiestrogens.

Base Sequence↗
PubMed1996

Observations on the free-living adult stage of Gordius dimorphus (Nematomorpha: Gordioidea).

A total of 119 adult hairworms, Gordius dimorphus, was collected on 2 occasions from a small mountain stream in New Zealand's South Island. Size dimorphism between male and female worms was much greater than previously reported. The average sizes of worms of either sex found in mixed-sex groups were no different from those of worms occurring either alone or in single-sex groups. In a sample taken in spring, the sex ratio was female biased, whereas in a sample from early summer the sex ratio was strongly male biased. A greater proportion of males was found in mixed-sex groups in early summer than in spring. Although laboratory experiments are needed, from the little evidence currently available it would appear that hairworms form mating groups more or less at random.

Animals↗
PubMed1995

Stable intracellular acidification upon polyamine depletion induced by alpha-difluoromethylornithine or N1,N12-bis(ethyl)spermine in L1210 leukaemia cells.

Polyamines play major roles in ionic and osmotic regulation, but their exact involvement in specific ion transport processes is poorly defined. Treatment of L1210 mouse leukaemia cells with either 5 mM alpha-difluoromethylornithine (DFMO), a suicide substrate of ornithine decarboxylase, or 25 microM N1,N12-bis(ethyl)spermine (BE-3-4-3), a dysfunctional polyamine analogue, caused a stable decreased in intracellular pH (pHi) by 0.1-0.4 unit from steady-state control values between 7.4 and 7.6, as measured either by partition of a weak acid or with a fluorescent pH-sensitive probe. This effect was not related to cell growth status or differences in metabolic acid generation, and was observed in either the presence or absence of HCO3-. Exogenous spermidine (10-25 microM) or putrescine (25-50 microM) fully reversed DFMO- or BE-3-4-3-induced acidification within 2 and 8 h respectively. Recovery of pHi in L1210 cells after a nigericin- or NH4(+)-mediated acid load in HCO3(-)-free buffers was mediated by Na+/H+ antiporter activity, in addition to a minor Na(+)-independent and amiloride-insensitive pathway. Decreased steady-state pHi was maintained in polyamine-depleted L1210 cells after recovery from acid stress. Moreover, the pHi-dependence of the rate of Na(+)-dependent H+ extrusion after an acid stress was altered by DFMO and BE-3-4-3, resulting in a set-point which was lower by 0.25-0.30 pH unit in polyamine-depleted cells. On the other hand, neither the rate nor the magnitude of Na+/H(+)-exchanger-mediated alkalinization induced by hypertonic shock was decreased by polyamine depletion. Thus polyamine depletion induces a persistent defect in pHi homeostasis which is due, at least in part, to a stable decrease in the pHi set-point of the Na+/H+ exchanger.

Animals↗
PubMed1995

Induction of apoptosis by excessive polyamine accumulation in ornithine decarboxylase-overproducing L1210 cells.

Deregulation of polyamine transport in L1210 cells overexpressing ornithine decarboxylase leads to a lethal accumulation of spermidine. We now provide evidence that over-accumulation of natural and synthetic polyamines, but not putrescine, rapidly induces apoptosis, as shown by hypercondensation of peripheral chromatin and internucleosomal cleavage, followed by nuclear fragmentation. Polyamine oxidation is not responsible for the apoptosis observed. Thus, abnormally high polyamine pools could be an important physiological trigger of apoptosis.

Animals↗
PubMed1995

Cleaning symbiosis as an evolutionary game: To cheat or not to cheat?

Cleaning symbiosis is an apparently mutualistic relationship, occurring in diverse taxa, in which cleaners remove ectoparasites from the body of their clients. Here its evolution is explored with a simple game theory model in which both participants play against each other using either honest or cheating strategies. Honest clients pose for cleaners and have their ectoparasites removed, cheating clients eat the cleaners. Honest cleaners eat their clients' ectoparasites, cheating cleaners feed mainly on client tissues. The conditions that favour either strategy are obtained when the game is resolved: (i) the cost of being cleaned by a cheat and the proportion of cheats in the cleaner population determine the relative value of honesty in clients, and (ii) the advantages of being an honest cleaner depend on the relative fitness value of ectoparasites as food versus client tissues. A scenario for the origin of the cleaning symbiosis can also be derived from the model, in which the specialization of both participants need not be simultaneous. The model is based on the relationship between specialized cleaner fish and their client fish on coral reefs, but its conclusions are used in an examination of other cleaning associations. Copyright 1995 Academic Press Limited

Journal Article↗
PubMed1995

Antiproliferative effect of spermine depletion by N-cyclohexyl-1,3-diaminopropane in human breast cancer cells.

Spermine is often the most abundant polyamine in human tumors such as breast carcinomas. However, its specific role in tumor biology is still uncertain, since inhibitors of ornithine decarboxylase such as alpha-difluoromethylornithine depress cell growth while leaving spermine content mostly unaffected. We have assessed the specific role of spermine in breast cancer cell growth using N-cyclohexyl-1,3-diaminopropane (C-DAP), a potent spermine synthase inhibitor. In ZR-75-1 cells, C-DAP decreased net cell growth after 14 days by 65% at 50 microm, with an IC50 of about 5 microM, and was about 10 times more potent than N-(n-butyl)-1,3-diaminopropane, another spermine synthase inhibitor. C-DAP acted as a specific inhibitor of spermine biosynthesis, since (a) it depleted spermine content while causing an equal or greater accumulation of spermidine on a molar basis, (b) it rapidly induced S-adenosylmethionine decarboxylase activity and the accumulation of its products due to relief of spermine-dependent inhibition of enzyme expression, and (c) exogenous spermine (1 microM) completely reversed C-DAP-induced growth inhibition. C-DAP and related compounds were accumulated, at least in part, through a mechanism distinct from the polyamine transport system, while also blocking putrescine and spermidine uptake with various potencies. Reversibility of C-DAP-induced growth inhibition by exogenous spermine was progressively lost on prolonged treatment, in association with marked morphological changes. In 4 different human breast cancer cell lines (ZR-75-1, T47-D, MCF-7, and MDA-MB-231), relative growth sensitivity to C-DAP was inversely related to the extent of spermidine accumulation caused by spermine synthase inhibition, suggesting that spermidine overaccumulation can functionally replace spermine. Interestingly, C-DAP strongly potentiated growth inhibition caused by alpha-difluoromethylornithine in all cell lines tested by preventing conversion of residual spermidine to spermine, indicating that spermine synthesis limits alpha-difluoromethylornithine action and that under some critical threshold, spermidine cannot fulfill cellular needs for spermine. Thus, spermine plays specific and important functions in breast tumor growth, and spermine synthase inhibitors could markedly improve the therapeutic effectiveness of existing polyamine depletion strategies, especially in spermine-rich tumors.

Biogenic Polyamines↗
PubMed1995

Inorganic cation dependence of putrescine and spermidine transport in human breast cancer cells.

The mechanism of polyamine uptake in mammalian cells is still poorly understood. The role of inorganic cations in polyamine transport was investigated in ZR-75-1 human breast cancer cells. Although strongly temperature dependent, neither putrescine nor spermidine uptake was mediated by a Na+ cotransport mechanism. In fact, Na+ and cholinium competitively inhibited putrescine uptake relative to that measured in a sucrose-based medium. On the other hand, ouabain, H+, Na+, and Ca2+ ionophores, as well as dissipation of the K+ diffusion potential, strongly inhibited polyamine uptake in keeping with a major role of membrane potential in that process. Polyamine transport was inversely dependent on ambient osmolality at near physiological values. Putrescine transport was inhibited by 70% by decreasing extracellular pH from 7.2 to 6.2, whereas spermidine uptake had a more acidic optimum. Deletion of extracellular Ca2+ inhibited putrescine uptake more strongly than chelation of intracellular Ca2+. In fact, bound divalent cations were absolutely required for polyamine transport, as shown after brief chelation of the cell monolayers with EDTA. Either Mn2+, Ca2+, or Mg2+ sustained putrescine uptake activity with high potency (Km = 50-300 microM). Mn2+ was a much stronger activator of spermidine than putrescine uptake, suggesting a specific role for this metal in polyamine transport. Other transition metals (Co2+, Ni2+, Cu2+, and Zn2+) were mixed activators/antagonists of carrier activity, while Sr2+ and Ba2+ were very weak agonists, while not interfering with Ca2+/Mg(2+)-dependent transport. Thus, polyamine uptake in human breast tumor cells is negatively affected by ionic strength and osmolality, and is driven, at least in part, by the membrane potential, but not by the Na+ electrochemical gradient. Moreover, the polyamine carrier, or a tightly coupled accessory component, appears to have a high-affinity binding site for divalent cations, which is essential for the uptake mechanism.

Biological Transport↗
PubMed1995

Hormonal and feedback regulation of putrescine and spermidine transport in human breast cancer cells.

The properties and regulation of the mammalian polyamine transport system are still poorly understood. In estrogen-responsive ZR-75-1 human breast cancer cells, which display low polyamine biosynthetic activity, putrescine and spermidine were internalized with high affinity (Km = 3.7 and 0.5 microM, respectively) via a single class of saturable transporter shared by both substrate types, or via distinct but closely similar carriers. The Vmax, but not the Km of polyamine transport was rapidly and synergistically up-regulated by estrogens and insulin. The steady decay in transport activity observed in hormone-deprived cells was accelerated by retinoic acid. The enhancement of uptake activity resulting from polyamine depletion was amplified 3-fold by estrogens and insulin despite profound growth inhibition, indicating that the cooperative hormonal induction of polyamine transport is dissociated from cell growth status. Polyamine uptake was under feedback inhibition by at least three distinct mechanisms in these cells, namely (i) the induction of a short-lived protein not actively synthesized without ongoing uptake or upon polyamine deletion; (ii) a more latent, protein synthesis-independent "trans-inhibition" mechanism; and (iii) a post-carrier, cycloheximide-sensitive mechanism limiting substrate accumulation. The complexity of these multiple levels of feedback transport inhibition is in keeping with the cytotoxicity of excessive polyamine content.

Biological Transport↗
PubMed1995

"Adaptive" changes in the behaviour of parasitized animals: a critical review.

Changes in host behaviour following infection with parasites are frequently reported in the literature, and are often hypothesized to be adaptive for either host or parasite. However, investigators of such phenomena often use the "adaptation" label for host behavioural changes based on their intuition and not on rigorous criteria. Alterations in host behaviour following infection can only be considered adaptive if they satisfy certain conditions: (1) they must be complex; (2) they must show signs of a purposive design; (3) they are more likely to be adaptations if they have arisen independently in several lineages of hosts or parasites; and (4) they must be shown to increase the fitness of either the host or the parasite. A survey of published examples of host behavioural changes indicates that while some are spectacularly complex and are extremely well-fitted to their presumed function, most are simple increases or decreases in an activity performed prior to infection. There are some suggestions of convergent evolution in behavioural change in distantly related host or parasite groups but more evidence is needed. Finally, most known behavioural changes have not been demonstrated to lead to fitness gains in either hosts or parasites. Few known examples satisfy more than two of the above criteria, and, in general, the adaptive function of changes in host behaviour following infection is in need of more solid proof.

Adaptation, Psychological↗
PubMed1995

Evolution of parasite life history traits: myths and reality.

Parasitism has evolved independently several times in many different animal lineages. Observations made on distantly related parasites have revealed a variety of adaptations to parasitism, including changes in physiology, morphology, and life history traits. These observations have led parasitologists to formulate general rules about the evolution of parasites, rules that define a common evolutionary path presumably followed by all parasitic organisms. Robert Poulin uses recent evidence to question the generality of these rules and to show that parasite evolution may take different roads. The selective pressures acting on parasites are diverse and may guide their evolution in any direction, just as they have shaped a wide variety of free-living organisms.

Journal Article↗
PubMed1995

Use of aminopropyltransferase inhibitors and of non-metabolizable analogs to study polyamine regulation and function.

The polyamines spermidine and spermine are essential for the growth of mammalian cells. This review describes the properties of the two aminopropyltransferases that are responsible for their biosynthesis, the synthesis and use of specific aminopropyltransferase inhibitors, and the use of analogs of the polyamines to investigate polyamine transport and function. Highly specific and potent multisubstrate adduct inhibitors of these enzymes have been synthesized while less potent inhibitors have been obtained by the synthesis of amines that bind at the active site. Studies with these inhibitors indicate that polyamines are needed for a normal rate of growth and that, although some of the functions of polyamines may be interchangeable, other functions may have a specific requirement for spermidine or spermine. Two groups of growth-promoting polyamine analogs can be distinguished: the many that are effective in short-term experiments compared to the few that can act over a prolonged period. The more stringent structural requirements for long-term growth are probably due to a need for spermidine, or a closely related analog, as a precursor of hypusine in the protein eIF-5A. Metabolically resistant polyamine analogs can be used as model substrates for studies of the polyamine transport system, which plays a critical role in maintaining normal cellular polyamine levels. The feedback regulation by high levels of polyamines that downregulates transport is essential to prevent the accumulation of polyamines at toxic levels. Such accumulation may be associated with apoptosis and, therefore, polyamine analogs are useful tools for investigating the mechanism(s) of polyamine-mediated toxicity.

Amino Acid Sequence↗
PubMed1995

Hairworms (Nematomorpha: Gordioidea) infecting New Zealand short-horned grasshoppers (Orthoptera: Acrididae).

A total of 282 short-horned grasshoppers (Acrididae) was collected in a mountainous area of New Zealand's South Island and examined for hairworm (Nematomorpha) infections. Thirteen percent of female Sigaus obelisci and 3% of female S. australis harbored hairworms; males of both species, as well as male and female S. campestris, were all uninfected. All hairworms recovered belong to the species Euchordodes nigromaculatus, previously known only from wetas (Orthoptera: Stenopelmatidae). No size differences were observed between infected and uninfected grasshoppers, and there was no relationship between host size and worm length. This is the first substantiated report of nematomorphs in grasshoppers in New Zealand.

Animals↗
PubMed1994

The evolution of parasite manipulation of host behaviour: a theoretical analysis.

Parasite-induced modifications of host behaviour are known from a wide range of host-parasite associations. In many cases, these behavioural changes are thought to be adaptive and benefit the parasite by increasing its probability of successful transmission. However, in many cases, energy spent on host manipulation will not be available for other functions, such as growth. These trade-offs suggest that in the absence of other constraints, natural selection will optimize, and not maximize, the influence of parasites on host behaviour. This argument is developed and expanded into theoretical considerations of the evolution of host behaviour manipulation by parasites. Among populations of the same parasite species or among closely-related species, the optimal investment into manipulation, or optimal manipulative effort (ME*), of individual parasites is predicted to increase as (1) typical infrapopulation size decreases, (2) prevalence increases, (3) the longevity of the infected host, or of the parasite in its host, decreases, (4) passive transmission rates decrease, and (5) parasite fecundity decreases. This evolutionary analysis indicates that ecological and life history variables may have played an important role in the evolution of manipulation of host behaviour by parasites.

Adaptation, Physiological↗