Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

Science.gov (United States)

Lefringhouse, Jason; Pavlik, Edward; Miller, Rachel; DeSimone, Christopher; Ueland, Frederick; Kryscio, Richard; van Nagell, J. R.

2014-01-01

Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy. PMID:25254047

Leishmania infantum EndoG is an endo/exo-nuclease essential for parasite survival.

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Eva Rico

Full Text Available EndoG, a member of the DNA/RNA non-specific ββα-metal family of nucleases, has been demonstrated to be present in many organisms, including Trypanosomatids. This nuclease participates in the apoptotic program in these parasites by migrating from the mitochondrion to the nucleus, where it takes part in the degradation of genomic DNA that characterizes this process. We now demonstrate that Leishmania infantum EndoG (LiEndoG is an endo-exonuclease that has a preferential 5' exonuclease activity on linear DNA. Regardless of its role during apoptotic cell death, this enzyme seems to be necessary during normal development of the parasites as indicated by the reduced growth rates observed in LiEndoG hemi-knockouts and their poor infectivity in differentiated THP-1 cells. The pro-life role of this protein is also corroborated by the higher survival rates of parasites that over-express this protein after treatment with the LiEndoG inhibitor Lei49. Taken together, our results demonstrate that this enzyme plays essential roles in both survival and death of Leishmania parasites.

Isolation of intracellular parasites (Plasmodium falciparum) from culture using free-flow electrophoresis: separation of the free parasites according to stages.

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Heidrich, H G; Mrema, J E; Vander Jagt, D L; Reyes, P; Rieckmann, K H

1982-06-01

Parasitized human erythrocytes were concentrated from continuous cultures of Plasmodium falciparum from 5-7% up to 80-95% using Plasmagel. After aggregation of the cells with phythemagglutinin, the aggregated erythrocytes were fragmented by passing them, with minimal force, through successive nylon filters of decreasing pore size (100 microns-3 microns). The mixture of liberated, free parasites, intact erythrocytes and erythrocyte membrane vesicles was separated using free-flow electrophoresis. Most of the fractions containing free parasites did not show contamination with erythrocyte constituents as determined by light and electron microscopy, polyacrylamide gel electrophoresis, and enzymatic analysis. In addition, the various stages of free parasites of Plasmodium falciparum exhibited different electrical surface charges. Rings and trophozoites were highly negatively charged whereas schizonts and, in particular, merozoites showed low negative charges. Thus, the various stages could be isolated separate from each other.

Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium.

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Susanne Helm

Full Text Available During the blood meal of a Plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. The Plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. Successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel to infect red blood cells. To successfully develop from the liver stage into infective merozoites, a tight regulation of gene expression is needed. Although this is a very interesting aspect in the biology of Plasmodium, little is known about gene regulation in Plasmodium parasites in general and in the liver stage in particular. We have functionally analyzed a novel promoter region of the rodent parasite Plasmodium berghei that is exclusively active during the liver stage of the parasite. To prove stage-specific activity of the promoter, GFP and luciferase reporter assays have been successfully established, allowing both qualitative and accurate quantitative analysis. To further characterize the promoter region, the transcription start site was mapped by rapid amplification of cDNA ends (5'-RACE. Using promoter truncation experiments and site-directed mutagenesis within potential transcription factor binding sites, we suggest that the minimal promoter contains more than one binding site for the recently identified parasite-specific ApiAP2 transcription factors. The identification of a liver stage-specific promoter in P. berghei confirms that the parasite is able to tightly regulate gene expression during its life cycle. The identified promoter region might now be used to study the biology of the Plasmodium liver stage, which has thus far proven problematic on a molecular level. Stage-specific expression of dominant-negative mutant proteins and

A Transcriptomic Analysis of Echinococcus granulosus Larval Stages: Implications for Parasite Biology and Host Adaptation

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Parkinson, John; Wasmuth, James D.; Salinas, Gustavo; Bizarro, Cristiano V.; Sanford, Chris; Berriman, Matthew; Ferreira, Henrique B.; Zaha, Arnaldo; Blaxter, Mark L.; Maizels, Rick M.; Fernández, Cecilia

2012-01-01

Background The cestode Echinococcus granulosus - the agent of cystic echinococcosis, a zoonosis affecting humans and domestic animals worldwide - is an excellent model for the study of host-parasite cross-talk that interfaces with two mammalian hosts. To develop the molecular analysis of these interactions, we carried out an EST survey of E. granulosus larval stages. We report the salient features of this study with a focus on genes reflecting physiological adaptations of different parasite stages. Methodology/Principal Findings We generated ∼10,000 ESTs from two sets of full-length enriched libraries (derived from oligo-capped and trans-spliced cDNAs) prepared with three parasite materials: hydatid cyst wall, larval worms (protoscoleces), and pepsin/H+-activated protoscoleces. The ESTs were clustered into 2700 distinct gene products. In the context of the biology of E. granulosus, our analyses reveal: (i) a diverse group of abundant long non-protein coding transcripts showing homology to a middle repetitive element (EgBRep) that could either be active molecular species or represent precursors of small RNAs (like piRNAs); (ii) an up-regulation of fermentative pathways in the tissue of the cyst wall; (iii) highly expressed thiol- and selenol-dependent antioxidant enzyme targets of thioredoxin glutathione reductase, the functional hub of redox metabolism in parasitic flatworms; (iv) candidate apomucins for the external layer of the tissue-dwelling hydatid cyst, a mucin-rich structure that is critical for survival in the intermediate host; (v) a set of tetraspanins, a protein family that appears to have expanded in the cestode lineage; and (vi) a set of platyhelminth-specific gene products that may offer targets for novel pan-platyhelminth drug development. Conclusions/Significance This survey has greatly increased the quality and the quantity of the molecular information on E. granulosus and constitutes a valuable resource for gene prediction on the parasite genome

Patch size and edge proximity are useful predictors of brood parasitism but not nest survival of grassland birds.

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Benson, Thomas J; Chiavacci, Scott J; Ward, Michael P

2013-06-01

Declines of migratory birds have led to increased focus on causative factors for these declines, including the potential adverse effects of habitat fragmentation on reproductive success. Although numerous studies have addressed how proximity to a habitat edge, patch size, or landscape context influence nest survival or brood parasitism, many have failed to find the purported effects. Furthermore, many have sought to generalize patterns across large geographic areas and habitats. Here, we examined evidence for effects of edge proximity, patch size, and landscape context on nest survival and brood parasitism of grassland birds, a group of conservation concern. The only consistent effect was a positive association between edge proximity and brood parasitism. We examined effects of patch size on nest survival (37 studies) and brood parasitism (30 studies) representing 170 and 97 different estimates, respectively, with a total sample size of > 14000 nests spanning eastern North America. Nest survival weakly increased with patch size in the Great Plains, but not in the Midwestern or Eastern United States, and brood parasitism was inversely related to patch size and consistently greater in the Great Plains. The consistency in brood parasitism relative to nest survival patterns is likely due to parasitism being caused by one species, while nest survival is driven by a diverse and variable suite of nest predators. Often, studies assume that predators responsible for nest predation, the main driver of nest success, either are the same or exhibit the same behaviors across large geographic areas. These results suggest that a better mechanistic understanding of nest predation is needed to provide meaningful conservation recommendations for improving grassland bird productivity, and that the use of general recommendations across large geographic areas should only be undertaken when sufficient data are available from all regions.

A plant/fungal-type phosphoenolpyruvate carboxykinase located in the parasite mitochondrion ensures glucose-independent survival of Toxoplasma gondii.

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Nitzsche, Richard; Günay-Esiyok, Özlem; Tischer, Maximilian; Zagoriy, Vyacheslav; Gupta, Nishith

2017-09-15

Toxoplasma gondii is considered to be one of the most successful intracellular pathogens, because it can reproduce in varied nutritional milieus, encountered in diverse host cell types of essentially any warm-blooded organism. Our earlier work demonstrated that the acute (tachyzoite) stage of T. gondii depends on cooperativity of glucose and glutamine catabolism to meet biosynthetic demands. Either of these two nutrients can sustain the parasite survival; however, what determines the metabolic plasticity has not yet been resolved. Here, we reveal two discrete phosphoenolpyruvate carboxykinase (PEPCK) enzymes in the parasite, one of which resides in the m i t ochondrion ( Tg PEPCK mt ), whereas the other protein is n ot e xpressed in t achyzoites ( Tg PEPCK net ). Parasites with an intact glycolysis can tolerate genetic deletions of Tg PEPCK mt as well as of Tg PEPCK net , indicating their nonessential roles for tachyzoite survival. Tg PEPCK net can also be ablated in a glycolysis-deficient mutant, while Tg PEPCK mt is refractory to deletion. Consistent with this, the lytic cycle of a conditional mutant of Tg PEPCK mt in the glycolysis-impaired strain was aborted upon induced repression of the mitochondrial isoform, demonstrating its essential role for the glucose-independent survival of parasites. Isotope-resolved metabolomics of the conditional mutant revealed defective flux of glutamine-derived carbon into RNA-bound ribose sugar as well as metabolites associated with gluconeogenesis, entailing a critical nodal role of PEPCK mt in linking catabolism of glucose and glutamine with anabolic pathways. Our data also suggest a homeostatic function of Tg PEPCK mt in cohesive operation of glycolysis and the tricarboxylic acid cycle in a normal glucose-replete milieu. Conversely, we found that the otherwise integrative enzyme pyruvate carboxylase ( Tg PyC) is dispensable not only in glycolysis-competent but also in glycolysis-deficient tachyzoites despite a mitochondrial

Climate change and parasite transmission: how temperature affects parasite infectivity via predation on infective stages

NARCIS (Netherlands)

Goedknegt, M.A.; Welsh, J.E.; Drent, J.; Thieltges, D.

2015-01-01

Climate change is expected to affect disease risk in many parasite-host systems, e.g., via an effect of temperature on infectivity (temperature effects). However, recent studies indicate that ambient communities can lower disease risk for hosts, for instance via predation on free-living stages of

Comparative anatomy and histology of developmental and parasitic stages in the life cycle of the lined sea anemone Edwardsiella lineata.

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Reitzel, Adam M; Daly, Marymegan; Sullivan, James C; Finnerty, John R

2009-02-01

The evolution of parasitism is often accompanied by profound changes to the developmental program. However, relatively few studies have directly examined the developmental evolution of parasitic species from free-living ancestors. The lined sea anemone Edwardsiella lineata is a relatively recently evolved parasite for which closely related free-living outgroups are known, including the starlet sea anemone Nematostella vectensis. The larva of E. lineata parasitizes the ctenophore Mnemiopsis leidyi, and, once embedded in its host, the anemone assumes a novel vermiform body plan. That we might begin to understand how the developmental program of this species has been transformed during the evolution of parasitism, we characterized the gross anatomy, histology, and cnidom of the parasitic stage, post-parasitic larval stage, and adult stage of the E. lineata life cycle. The distinct parasitic stage of the life cycle differs from the post-parasitic larva with respect to overall shape, external ciliation, cnida frequency, and tissue architecture. The parasitic stage and planula both contain holotrichs, a type of cnida not previously reported in Edwardsiidae. The internal morphology of the post-parasitic planula is extremely similar to the adult morphology, with a complete set of mesenterial tissue and musculature despite this stage having little external differentiation. Finally, we observed 2 previously undocumented aspects of asexual reproduction in E. lineata: (1) the parasitic stage undergoes transverse fission via physal pinching, the first report of asexual reproduction in a pre-adult stage in the Edwardsiidae; and (2) the juvenile polyp undergoes transverse fission via polarity reversal, the first time this form of fission has been reported in E. lineata.

Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

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Rachel E Sutherland

Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

A PKA survival pathway inhibited by DPT-PKI, a new specific cell permeable PKA inhibitor, is induced by T. annulata in parasitized B-lymphocytes.

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Guergnon, Julien; Dessauge, Frederic; Traincard, François; Cayla, Xavier; Rebollo, Angelita; Bost, Pierre Etienne; Langsley, Gordon; Garcia, Alphonse

2006-08-01

T. annulata, an intracellular pathogenic parasite of the Aplicomplexa protozoan family infects bovine B-lymphocytes and macrophages. Parasitized cells that become transformed survive and proliferate independently of exogenous growth factors. In the present study, we used the isogenic non parasitized BL3 and parasitized TBL3 B cell lines, as a model to evaluate the contribution of two-major PI3-K- and PKA-dependent anti-apoptotic pathways in the survival of T. annulata parasitized B lymphocytes. We found that T. annulata increases PKA activity, induces over-expression of the catalytic subunit and down-regulates the pro-survival phosphorylation state of Akt/PKB. Consistent with a role of PKA activation in survival, two pharmacological inhibitors H89 and KT5720 ablate PKA-dependent survival of parasitized cells. To specifically inhibit PKA pro-survival pathways we linked the DPTsh1 peptide shuttle sequence to PKI(5-24) and we generated DPT-PKI, a cell permeable PKI. DPT-PKI specifically inhibited PKA activity in bovine cell extracts and, as expected, also inhibited the PKA-dependent survival of T. annulata parasitized TBL3 cells. Thus, parasite-dependent constitutive activation of PKA in TBL3 cells generates an anti-apoptotic pathway that can protect T. annulata-infected B cells from apoptosis. These results also indicate that DPT-PKI could be a powerful tool to inhibit PKA pathways in other cell types.

A novel genetic technique in Plasmodium berghei allows liver stage analysis of genes required for mosquito stage development and demonstrates that de novo heme synthesis is essential for liver stage development in the malaria parasite.

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Upeksha L Rathnapala

2017-06-01

Full Text Available The combination of drug resistance, lack of an effective vaccine, and ongoing conflict and poverty means that malaria remains a major global health crisis. Understanding metabolic pathways at all parasite life stages is important in prioritising and targeting novel anti-parasitic compounds. The unusual heme synthesis pathway of the rodent malaria parasite, Plasmodium berghei, requires eight enzymes distributed across the mitochondrion, apicoplast and cytoplasm. Deletion of the ferrochelatase (FC gene, the final enzyme in the pathway, confirms that heme synthesis is not essential in the red blood cell stages of the life cycle but is required to complete oocyst development in mosquitoes. The lethality of FC deletions in the mosquito stage makes it difficult to study the impact of these mutations in the subsequent liver stage. To overcome this, we combined locus-specific fluorophore expression with a genetic complementation approach to generate viable, heterozygous oocysts able to produce a mix of FC expressing and FC deficient sporozoites. These sporozoites show normal motility and can invade liver cells, where FC deficient parasites can be distinguished by fluorescence and phenotyped. Parasites lacking FC exhibit a severe growth defect within liver cells, with development failure detectable in the early to mid stages of liver development in vitro. FC deficient parasites could not complete liver stage development in vitro nor infect naïve mice, confirming liver stage arrest. These results validate the heme pathway as a potential target for prophylactic drugs targeting liver stage parasites. In addition, we demonstrate that our simple genetic approach can extend the phenotyping window beyond the insect stages, opening considerable scope for straightforward reverse genetic analysis of genes that are dispensable in blood stages but essential for completing mosquito development.

A novel genetic technique in Plasmodium berghei allows liver stage analysis of genes required for mosquito stage development and demonstrates that de novo heme synthesis is essential for liver stage development in the malaria parasite.

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Rathnapala, Upeksha L; Goodman, Christopher D; McFadden, Geoffrey I

2017-06-01

The combination of drug resistance, lack of an effective vaccine, and ongoing conflict and poverty means that malaria remains a major global health crisis. Understanding metabolic pathways at all parasite life stages is important in prioritising and targeting novel anti-parasitic compounds. The unusual heme synthesis pathway of the rodent malaria parasite, Plasmodium berghei, requires eight enzymes distributed across the mitochondrion, apicoplast and cytoplasm. Deletion of the ferrochelatase (FC) gene, the final enzyme in the pathway, confirms that heme synthesis is not essential in the red blood cell stages of the life cycle but is required to complete oocyst development in mosquitoes. The lethality of FC deletions in the mosquito stage makes it difficult to study the impact of these mutations in the subsequent liver stage. To overcome this, we combined locus-specific fluorophore expression with a genetic complementation approach to generate viable, heterozygous oocysts able to produce a mix of FC expressing and FC deficient sporozoites. These sporozoites show normal motility and can invade liver cells, where FC deficient parasites can be distinguished by fluorescence and phenotyped. Parasites lacking FC exhibit a severe growth defect within liver cells, with development failure detectable in the early to mid stages of liver development in vitro. FC deficient parasites could not complete liver stage development in vitro nor infect naïve mice, confirming liver stage arrest. These results validate the heme pathway as a potential target for prophylactic drugs targeting liver stage parasites. In addition, we demonstrate that our simple genetic approach can extend the phenotyping window beyond the insect stages, opening considerable scope for straightforward reverse genetic analysis of genes that are dispensable in blood stages but essential for completing mosquito development.

Discovery of HDAC inhibitors with potent activity against multiple malaria parasite life cycle stages.

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Hansen, Finn K; Sumanadasa, Subathdrage D M; Stenzel, Katharina; Duffy, Sandra; Meister, Stephan; Marek, Linda; Schmetter, Rebekka; Kuna, Krystina; Hamacher, Alexandra; Mordmüller, Benjamin; Kassack, Matthias U; Winzeler, Elizabeth A; Avery, Vicky M; Andrews, Katherine T; Kurz, Thomas

2014-07-23

In this work we investigated the antiplasmodial activity of a series of HDAC inhibitors containing an alkoxyamide connecting-unit linker region. HDAC inhibitor 1a (LMK235), previously shown to be a novel and specific inhibitor of human HDAC4 and 5, was used as a starting point to rapidly construct a mini-library of HDAC inhibitors using a straightforward solid-phase supported synthesis. Several of these novel HDAC inhibitors were found to have potent in vitro activity against asexual stage Plasmodium falciparum malaria parasites. Representative compounds were shown to hyperacetylate P. falciparum histones and to inhibit deacetylase activity of recombinant PfHDAC1 and P. falciparum nuclear extracts. All compounds were also screened in vitro for activity against Plasmodium berghei exo-erythrocytic stages and selected compounds were further tested against late stage (IV and V) P. falciparum gametocytes. Of note, some compounds showed nanomolar activity against all three life cycle stages tested (asexual, exo-erythrocytic and gametocyte stages) and several compounds displayed significantly increased parasite selectivity compared to the reference HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). These data suggest that it may be possible to develop HDAC inhibitors that target multiple malaria parasite life cycle stages. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Bot fly parasitism of the red-backed vole: host survival, infection risk, and population growth.

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Lemaître, Jérôme; Fortin, Daniel; Montiglio, Pierre-Olivier; Darveau, Marcel

2009-03-01

Parasites can play an important role in the dynamics of host populations, but empirical evidence remains sparse. We investigated the role of bot fly (Cuterebra spp.) parasitism in red-backed voles (Myodes gapperi) by first assessing the impacts of the parasite on the probability of vole survival under stressful conditions as well as on the reproductive activity of females. We then identified the main factors driving both the individual risk of infection and the abundance of bot flies inside red-backed voles. Finally, we evaluated the impacts of bot fly prevalence on the growth rate of vole populations between mid-July and mid-August. Thirty-six populations of red-backed voles were sampled in the boreal forest of Québec, Canada. The presence and the abundance of parasites in voles, two host life history traits (sex and body condition), three indices of habitat complexity (tree basal area, sapling basal area, coarse woody debris volume), and vole abundance were considered in models evaluating the effects of bot flies on host populations. We found that the probability of survival of red-backed voles in live traps decreased with bot fly infection. Both the individual risk of infection and the abundance of bot flies in red-backed voles were driven mainly by vole abundance rather than by the two host life history traits or the three variables of habitat complexity. Parasitism had population consequences: bot fly prevalence was linked to a decrease in short-term growth rate of vole populations over the summer. We found that bot flies have the potential to reduce survival of red-backed voles, an effect that may apply to large portions of populations.

Lysine acetylation in sexual stage malaria parasites is a target for antimalarial small molecules.

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Trenholme, Katharine; Marek, Linda; Duffy, Sandra; Pradel, Gabriele; Fisher, Gillian; Hansen, Finn K; Skinner-Adams, Tina S; Butterworth, Alice; Ngwa, Che Julius; Moecking, Jonas; Goodman, Christopher D; McFadden, Geoffrey I; Sumanadasa, Subathdrage D M; Fairlie, David P; Avery, Vicky M; Kurz, Thomas; Andrews, Katherine T

2014-07-01

Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination agenda. Primaquine is currently the only drug with such activity; however, its use is limited by side effects. The development of transmission-blocking strategies requires an understanding of sexual stage malaria parasite (gametocyte) biology and the identification of new drug leads. Lysine acetylation is an important posttranslational modification involved in regulating eukaryotic gene expression and other essential processes. Interfering with this process with histone deacetylase (HDAC) inhibitors is a validated strategy for cancer and other diseases, including asexual stage malaria parasites. Here we confirm the expression of at least one HDAC protein in Plasmodium falciparum gametocytes and show that histone and nonhistone protein acetylation occurs in this life cycle stage. The activity of the canonical HDAC inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; Vorinostat) and a panel of novel HDAC inhibitors on early/late-stage gametocytes and on gamete formation was examined. Several compounds displayed early/late-stage gametocytocidal activity, with TSA being the most potent (50% inhibitory concentration, 70 to 90 nM). In contrast, no inhibitory activity was observed in P. falciparum gametocyte exflagellation experiments. Gametocytocidal HDAC inhibitors caused hyperacetylation of gametocyte histones, consistent with a mode of action targeting HDAC activity. Our data identify HDAC inhibitors as being among a limited number of compounds that target both asexual and sexual stage malaria parasites, making them a potential new starting point for gametocytocidal drug leads and valuable tools for dissecting gametocyte biology. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Taxonomy and ecology of metazoan parasites of otariids from Patagonia, Argentina : adult and infective stages

OpenAIRE

Hernández Orts, Jesús Servando

2013-01-01

At present, the metazoan parasite fauna of most species of otariids is generally poorly known, in part because these marine mammals are mostly protected and, therefore, sampling is limited to specimens stranded on the coast or captured as by-catch in fisheries. Similar problems also occur for the larval stages of gastrointestinal helminths of otariids. For most of these parasite species, the specific identity of the intermediate/paratenic of hosts is unknown and, therefore, many stages of the...

The parasitic castration and gigantism of Lymnaea truncatula infected with the larval stages of Fasciola hepatica.

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Wilson, R A; Denison, J

1980-01-01

The shells of Lymnaea truncatula infected with the larval stages of Fasciola hepatica were significantly longer than those of comparable uninfected controls. The dry mass (tissue, shell + parasite) of the same infected snails, 56 days after infection, was approximately twice that of the controls (tissue + shell). The increased mass of infected snails was not due to a disproportionate increase in shell weight relative to tissues. Infected snails maintained at 20 degrees C had virtually ceased egg production by 21 days post-infection whereas control snails continued to lay eggs steadily for the duration of the experiment. The dry mass of snail tissue plus the cumulative dry weight of eggs produced was taken as an indication of the ability of control snails to generate biomass. Similarly the tissue mass plus cumulative egg weight and parasite weight was taken as an indication of the ability of the infected snails to generate biomass. The control and infected snails were not significantly different in this respect indicating that the gigantism of infected snails could be the result of a switch in nutrient supply from reproduction to somatic tissue growth and parasite growth. Castration was brought about 17-21 days after infection as a result of the direct consumption of the ovotestis by a proportion of the redial population. In a separate experiment it was demonstrated that a population of infected snails maintained at 20 degrees C survived as long as a similar group of control snails. The findings with this host-parasite system are discussed in relation to possible mechanisms causing castration and gigantism in other digene-snail interactions, and in relation to parasitic castration in other groups. It is concluded that the observed gigantism of infected snails is more likely to have a nutritional rather than endocrine origin.

The Puf-family RNA-binding protein Puf2 controls sporozoite conversion to liver stages in the malaria parasite.

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Katja Müller

Full Text Available Malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus Plasmodium. During host switch the malaria parasite employs specialized latent stages that colonize the new host environment. Previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. Sexual parasite development is controlled by a DEAD-box RNA helicase of the DDX6 family, termed DOZI. Latency of sporozoites, the transmission stage injected during an infectious blood meal, is controlled by the eIF2alpha kinase IK2, a general inhibitor of protein synthesis. Whether RNA-binding proteins participate in translational regulation in sporozoites remains to be studied. Here, we investigated the roles of two RNA-binding proteins of the Puf-family, Plasmodium Puf1 and Puf2, during sporozoite stage conversion. Our data reveal that, in the rodent malaria parasite P. berghei, Puf2 participates in the regulation of IK2 and inhibits premature sporozoite transformation. Inside mosquito salivary glands puf2⁻ sporozoites transform over time to round forms resembling early intra-hepatic stages. As a result, mutant parasites display strong defects in initiating a malaria infection. In contrast, Puf1 is dispensable in vivo throughout the entire Plasmodium life cycle. Our findings support the notion of a central role for Puf2 in parasite latency during switch between the insect and mammalian hosts.

Food webs including parasites, biomass, body sizes, and life stages for three California/Baja California estuaries

Science.gov (United States)

Hechinger, Ryan F.; Lafferty, Kevin D.; McLaughlin, John P.; Fredensborg, Brian L.; Huspeni, Todd C.; Lorda, Julio; Sandhu, Parwant K.; Shaw, Jenny C.; Torchin, Mark E.; Whitney, Kathleen L.; Kuris, Armand M.

2001-01-01

This data set presents food webs for three North American Pacific coast estuaries and a “Metaweb” composed of the species/stages compiled from all three estuaries. The webs have four noteworthy attributes: (1) parasites (infectious agents), (2) body-size information, (3) biomass information, and (4) ontogenetic stages of many animals with complex life cycles. The estuaries are Carpinteria Salt Marsh, California (CSM); Estero de Punta Banda, Baja California (EPB); and Bahía Falsa in Bahía San Quintín, Baja California (BSQ). Most data on species assemblages and parasitism were gathered via consistent sampling that acquired body size and biomass information for plants and animals larger than ∼1 mm, and for many infectious agents (mostly metazoan parasites, but also some microbes). We augmented this with information from additional published sources and by sampling unrepresented groups (e.g., plankton). We estimated free-living consumer–resource links primarily by extending a previously published version of the CSM web (which the current CSM web supplants) and determined most parasite consumer–resource links from direct observation. We recognize 21 possible link types including four general interactions: predators consuming prey, parasites consuming hosts, predators consuming parasites, and parasites consuming parasites. While generally resolved to the species level, we report stage-specific nodes for many animals with complex life cycles. We include additional biological information for each node, such as taxonomy, lifestyle (free-living, infectious, commensal, mutualist), mobility, and residency. The Metaweb includes 500 nodes, 314 species, and 11 270 links projected to be present given appropriate species' co-occurrences. Of these, 9247 links were present in one or more of the estuarine webs. The remaining 2023 links were not present in the estuaries but are included here because they may occur in other places or times. Initial analyses have examined

Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum.

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Brancucci, Nicolas M B; Gerdt, Joseph P; Wang, ChengQi; De Niz, Mariana; Philip, Nisha; Adapa, Swamy R; Zhang, Min; Hitz, Eva; Niederwieser, Igor; Boltryk, Sylwia D; Laffitte, Marie-Claude; Clark, Martha A; Grüring, Christof; Ravel, Deepali; Blancke Soares, Alexandra; Demas, Allison; Bopp, Selina; Rubio-Ruiz, Belén; Conejo-Garcia, Ana; Wirth, Dyann F; Gendaszewska-Darmach, Edyta; Duraisingh, Manoj T; Adams, John H; Voss, Till S; Waters, Andrew P; Jiang, Rays H Y; Clardy, Jon; Marti, Matthias

2017-12-14

Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A Novel Meloidogyne incognita Effector Misp12 Suppresses Plant Defense Response at Latter Stages of Nematode Parasitism

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Xie, Jialian; Li, Shaojun; Mo, Chenmi; Wang, Gaofeng; Xiao, Xueqiong; Xiao, Yannong

2016-01-01

Secreted effectors in plant root-knot nematodes (RKNs, or Meloidogyne spp.) play key roles in their parasite processes. Currently identified effectors mainly focus on the early stage of the nematode parasitism. There are only a few reports describing effectors that function in the latter stage. In this study, we identified a potential RKN effector gene, Misp12, that functioned during the latter stage of parasitism. Misp12 was unique in the Meloidogyne spp., and highly conserved in Meloidogyne incognita. It encoded a secretory protein that specifically expressed in the dorsal esophageal gland, and highly up-regulated during the female stages. Transient expression of Misp12-GUS-GFP in onion epidermal cell showed that Misp12 was localized in cytoplast. In addition, in planta RNA interference targeting Misp12 suppressed the expression of Misp12 in nematodes and attenuated parasitic ability of M. incognita. Furthermore, up-regulation of jasmonic acid (JA) and salicylic acid (SA) pathway defense-related genes in the virus-induced silencing of Misp12 plants, and down-regulation of SA pathway defense-related genes in Misp12-expressing plants indicated the gene might be associated with the suppression of the plant defense response. These results demonstrated that the novel nematode effector Misp12 played a critical role at latter parasitism of M. incognita. PMID:27446188

Effect of hydronephrosis on survival in advanced stage cervical cancer.

Science.gov (United States)

Goklu, Mehmet Rıfat; Seckin, Kerem Doga; Togrul, Cihan; Goklu, Yasemin; Tahaoglu, Ali Emre; Oz, Murat; Ertas, Ibrahim Egemen

2015-01-01

Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (phydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (pHydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be stratified into subgroups according to presence or absence of hydronephrosis.

Cyclosporin A treatment of Leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability.

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Wai-Lok Yau

Full Text Available BACKGROUND: Cyclosporin A (CsA has important anti-microbial activity against parasites of the genus Leishmania, suggesting CsA-binding cyclophilins (CyPs as potential drug targets. However, no information is available on the genetic diversity of this important protein family, and the mechanisms underlying the cytotoxic effects of CsA on intracellular amastigotes are only poorly understood. Here, we performed a first genome-wide analysis of Leishmania CyPs and investigated the effects of CsA on host-free L. donovani amastigotes in order to elucidate the relevance of these parasite proteins for drug development. METHODOLOGY/PRINCIPAL FINDINGS: Multiple sequence alignment and cluster analysis identified 17 Leishmania CyPs with significant sequence differences to human CyPs, but with highly conserved functional residues implicated in PPIase function and CsA binding. CsA treatment of promastigotes resulted in a dose-dependent inhibition of cell growth with an IC50 between 15 and 20 microM as demonstrated by proliferation assay and cell cycle analysis. Scanning electron microscopy revealed striking morphological changes in CsA treated promastigotes reminiscent to developing amastigotes, suggesting a role for parasite CyPs in Leishmania differentiation. In contrast to promastigotes, CsA was highly toxic to amastigotes with an IC50 between 5 and 10 microM, revealing for the first time a direct lethal effect of CsA on the pathogenic mammalian stage linked to parasite thermotolerance, independent from host CyPs. Structural modeling, enrichment of CsA-binding proteins from parasite extracts by FPLC, and PPIase activity assays revealed direct interaction of the inhibitor with LmaCyP40, a bifunctional cyclophilin with potential co-chaperone function. CONCLUSIONS/SIGNIFICANCE: The evolutionary expansion of the Leishmania CyP protein family and the toxicity of CsA on host-free amastigotes suggest important roles of PPIases in parasite biology and implicate

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

Science.gov (United States)

2009-01-01

Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On

Immune escape strategies of malaria parasites

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Pollyanna Stephanie Gomes

2016-10-01

Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

Survival and reproductive rate of mites in relation to resistance of their barn swallow hosts.

Science.gov (United States)

Møller, A P

2000-08-01

Parasite resistance may act via a number of different mechanisms that regulate or control the survival and the reproductive rate of parasites. Observations and experiments were used to test for effects of host resistance on parasite survival and rate of reproduction. Natural levels of infestation of barn swallow Hirundo rustica nests by the tropical fowl mite Ornithonyssus bursa were positively related to brood size, inversely related to the length of the outermost tail feathers of male nest owners (a secondary sexual character) and affected by time of reproduction by the host. A mite inoculation experiment, in which 50 adult mites were introduced into nests during the laying period of the host, was used to test for differential survival and reproduction of mites as a function of host resistance. The relationship between survival and reproduction of parasites, male tail length and host resistance was investigated. There was a negative relationship between mite numbers per nest after fledging of nestlings and male tail length. This relationship was mainly caused by a reduction in the number of mites in the first and second nymph stage with increasing tail length of male hosts, implying a reduction in rate of reproduction of mites. The proportion of mites that had recently fed was inversely related to tail length of male hosts. The proportion of nymph stages was positively related to the proportion of mites that had recently had a blood meal. Parasite resistance of barn swallows to the tropical fowl mite thus appeared to act through increased mortality rate of adult and nymph stages of mites, and through reduced reproductive rates of mites on resistant hosts. This is the first study demonstating a direct relationship between fitness components of a parasite and the expression of a secondary sexual character of a host.

Parasitic nematode interactions with mammals and plants.

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Jasmer, Douglas P; Goverse, Aska; Smant, Geert

2003-01-01

Parasitic nematodes that infect humans, animals, and plants cause serious diseases that are deleterious to human health and agricultural productivity. Chemical and biological control methods have reduced the impact of these parasites. However, surviving environmental stages lead to persistent reinfection of host species. In addition, development of resistance to nematicides and anthelmintics by these parasites and reduced availability of some nematicides, for environmental protection, pose significant obstacles for current and future prospects of effective parasite control. Due to marked differences in host species, research on animal and plant parasitic nematodes often proceeds independently. Despite the differences between animals and plants, basic cellular properties are shared among these host organisms. Some common properties may be important for mechanisms [homologous or convergent (homoplastic)] by which nematodes successfully infect these diverse hosts or by which animal and plant hosts resist infections by these pathogens. Here we compare host/parasite interactions between plant parasitic nematodes (PPN) and animal parasitic nematodes, with an emphasis on mammalian hosts (MPN). Similarities and differences are considered in the context of progress on molecular dissection of these interactions. A comprehensive coverage is not possible in the space allotted. Instead, an illustrative approach is used to establish examples that, it is hoped, exemplify the value of the comparative approach.

The relation between lymph node status and survival in Stage I-III colon cancer

DEFF Research Database (Denmark)

Lykke, J.; Roikjær, Ole; Jess, P.

2013-01-01

Aim: This study involved a large nationwide Danish cohort to evaluate the hypothesis that a high lymph node harvest has a positive effect on survival in curative resected Stage I-III colon cancer and a low lymph node ratio has a positive effect on survival in Stage III colon cancer. Method......: Analysis of overall survival was conducted using a nationwide Danish cohort of patients treated with curative resection of Stage I-III colon cancer. All 8901 patients in Denmark diagnosed with adenocarcinoma of the colon and treated with curative resection in the period 2003-2008 were identified from...... independent prognostic factors in multivariate analysis. Conclusion: High lymph node count was associated with improved overall survival in colon cancer. Lymph node ratio was superior to N-stage in differentiating overall survival in Stage III colon cancer. Stage migration was observed....

A peroxidase gene expressed during early developmental stages of the parasitic plant Orobanche ramosa.

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González-Verdejo, Clara Isabel; Barandiaran, Xabier; Moreno, Maria Teresa; Cubero, José Ignacio; Di Pietro, Antonio

2006-01-01

Broomrapes (Orobanche spp.) are holoparasitic weeds that cause devastating losses in many economically important crops. The molecular mechanisms that control the early stages of host infection in Orobanche are poorly understood. In the present study, the role of peroxidase has been examined during pre-infection growth and development of O. ramosa, using an in vitro model system. Peroxidase activity was histochemically localized at the tips of actively growing radicles and nascent attachment organs. Addition of exogenous catalase resulted in a significant reduction in the apical growth rate of the radicle. The prx1 gene encoding a putative class III peroxidase was cloned from a cDNA library of O. ramosa and was found to be expressed specifically during the early stages of the parasitic life cycle. The exogenous addition of sucrose resulted in significantly reduced prx1 transcript levels and in a dramatic change in radicle development from polarized apical growth to isotropic growth and the formation of tubercle-like structures. The results indicate an important role of peroxidases during the early parasitic stages of Orobanche.

Host age modulates parasite infectivity, virulence and reproduction.

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Izhar, Rony; Ben-Ami, Frida

2015-07-01

Host age is one of the most striking differences among hosts within most populations, but there is very little data on how age-dependent effects impact ecological and evolutionary dynamics of both the host and the parasite. Here, we examined the influence of host age (juveniles, young and old adults) at parasite exposure on host susceptibility, fecundity and survival as well as parasite transmission, using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa. Younger D. magna were more susceptible to infection than older ones, regardless of host or parasite clone. Also, younger-infected D. magna became castrated faster than older hosts, but host and parasite clone effects contributed to this trait as well. Furthermore, the early-infected D. magna produced considerably more parasite transmission stages than late-infected ones, while host age at exposure did not affect virulence as it is defined in models (host mortality). When virulence is defined more broadly as the negative effects of infection on host fitness, by integrating the parasitic effects on host fecundity and mortality, then host age at exposure seems to slide along a negative relationship between host and parasite fitness. Thus, the virulence-transmission trade-off differs strongly among age classes, which in turn affects predictions of optimal virulence. Age-dependent effects on host susceptibility, virulence and parasite transmission could pose an important challenge for experimental and theoretical studies of infectious disease dynamics and disease ecology. Our results present a call for a more explicit stage-structured theory for disease, which will incorporate age-dependent epidemiological parameters. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Stress and sex in malaria parasites: Why does commitment vary?

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Carter, Lucy M; Kafsack, Björn F C; Llinás, Manuel; Mideo, Nicole; Pollitt, Laura C; Reece, Sarah E

2013-01-01

For vector-borne parasites such as malaria, how within- and between-host processes interact to shape transmission is poorly understood. In the host, malaria parasites replicate asexually but for transmission to occur, specialized sexual stages (gametocytes) must be produced. Despite the central role that gametocytes play in disease transmission, explanations of why parasites adjust gametocyte production in response to in-host factors remain controversial. We propose that evolutionary theory developed to explain variation in reproductive effort in multicellular organisms, provides a framework to understand gametocyte investment strategies. We examine why parasites adjust investment in gametocytes according to the impact of changing conditions on their in-host survival. We then outline experiments required to determine whether plasticity in gametocyte investment enables parasites to maintain fitness in a variable environment. Gametocytes are a target for anti-malarial transmission-blocking interventions so understanding plasticity in investment is central to maximizing the success of control measures in the face of parasite evolution.

Empirical support for optimal virulence in a castrating parasite.

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Knut Helge Jensen

2006-07-01

Full Text Available The trade-off hypothesis for the evolution of virulence predicts that parasite transmission stage production and host exploitation are balanced such that lifetime transmission success (LTS is maximised. However, the experimental evidence for this prediction is weak, mainly because LTS, which indicates parasite fitness, has been difficult to measure. For castrating parasites, this simple model has been modified to take into account that parasites convert host reproductive resources into transmission stages. Parasites that kill the host too early will hardly benefit from these resources, while postponing the killing of the host results in diminished returns. As predicted from optimality models, a parasite inducing castration should therefore castrate early, but show intermediate levels of virulence, where virulence is measured as time to host killing. We studied virulence in an experimental system where a bacterial parasite castrates its host and produces spores that are not released until after host death. This permits estimating the LTS of the parasite, which can then be related to its virulence. We exposed replicate individual Daphnia magna (Crustacea of one host clone to the same amount of bacterial spores and followed individuals until their death. We found that the parasite shows strong variation in the time to kill its host and that transmission stage production peaks at an intermediate level of virulence. A further experiment tested for the genetic basis of variation in virulence by comparing survival curves of daphniids infected with parasite spores obtained from early killing versus late killing infections. Hosts infected with early killer spores had a significantly higher death rate as compared to those infected with late killers, indicating that variation in time to death was at least in part caused by genetic differences among parasites. We speculate that the clear peak in lifetime reproductive success at intermediate killing times

Survival and growth of parasitic Maculinea alcon caterpillars (Lepidoptera: Lycaenidae) in nests of three Myrmica ant species

DEFF Research Database (Denmark)

Nash, D. R.; Als, Thomas Damm; Boomsma, J. J.

2011-01-01

The Alcon blue butterfly (Maculinea alcon) parasitizes the nests of several Myrmica ant species. In Denmark, it uses M. rubra and M. ruginodis, but never M. scabrinodis. To further examine the basis of this specificity and local co-adaptation between host and parasite, the pattern of growth...... and survival of newly-adopted caterpillars of M. alcon in Myrmica subcolonies was examined in the laboratory. M. alcon caterpillars were collected from three populations differing in their host use, and reared in laboratory nests of all three ant species collected from each M. alcon population. While...... there were differences in the pattern of growth of caterpillars from different populations during the first few months after adoption, which depended on host ant species and the site from which the ants were collected, there was no evidence of major differences in final size achieved. Survival was, however...

Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

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Erica S Martins-Duarte

Full Text Available Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite's DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM. When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13-25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment. Light microscopy examination early (6 and 24h post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition--with the appearance of 'tethered' parasites--malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results

Sunflower Resistance to Broomrape (Orobanche cumana) Is Controlled by Specific QTLs for Different Parasitism Stages.

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Louarn, Johann; Boniface, Marie-Claude; Pouilly, Nicolas; Velasco, Leonardo; Pérez-Vich, Begoña; Vincourt, Patrick; Muños, Stéphane

2016-01-01

Orobanche cumana (sunflower broomrape) is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation. In our study, we used a population of 101 recombinant inbred lines (RILs), derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with Helianthus debilis). Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i) early attachment of the parasite to the sunflower roots, (ii) young tubercle and (iii) shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey) and for the three stages of broomrape development. The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding.

Sunflower resistance to broomrape (Orobanche cumana is controlled by specific QTLs for different parasitism stages

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Johann eLouarn

2016-05-01

Full Text Available Orobanche cumana (sunflower broomrape is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation.In our study, we used a population of 101 recombinant inbred lines (RILs, derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with H. debilis. Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i early attachment of the parasite to the sunflower roots, (ii young tubercle and (iii shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey and for the three stages of broomrape development.The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding.

Sunflower Resistance to Broomrape (Orobanche cumana) Is Controlled by Specific QTLs for Different Parasitism Stages

Science.gov (United States)

Louarn, Johann; Boniface, Marie-Claude; Pouilly, Nicolas; Velasco, Leonardo; Pérez-Vich, Begoña; Vincourt, Patrick; Muños, Stéphane

2016-01-01

Orobanche cumana (sunflower broomrape) is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation. In our study, we used a population of 101 recombinant inbred lines (RILs), derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with Helianthus debilis). Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i) early attachment of the parasite to the sunflower roots, (ii) young tubercle and (iii) shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey) and for the three stages of broomrape development. The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding. PMID:27242810

Plasmodium Apicoplast Gln-tRNA Gln Biosynthesis Utilizes a Unique GatAB Amidotransferase Essential for Erythrocytic Stage Parasites

KAUST Repository

Mailu, Boniface M.; Li, Ling; Arthur, Jen; Nelson, Todd M.; Ramasamy, Gowthaman; Fritz-Wolf, Karin; Becker, Katja; Gardner, Malcolm J.

2015-01-01

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. The malaria parasite Plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-tRNA synthetase to synthesize Glu-tRNAGln and a glutaminyl-tRNA amidotransferase to convert Glu-tRNAGln to Gln-tRNAGln. Here, we show that Plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyltRNA amidotransferase consisting of GatA and GatB subunits (GatAB). We localized the P. falciparum GatA and GatB subunits to the apicoplast in blood stage parasites and demonstrated that recombinant GatAB converts Glu-tRNAGln to Gln-tRNAGln in vitro. We demonstrate that the apicoplast GatAB-catalyzed reaction is essential to the parasite blood stages because we could not delete the Plasmodium berghei gene encoding GatA in blood stage parasites in vivo. A phylogenetic analysis placed the split between Plasmodium GatB, archaeal GatE, and bacterial GatB prior to the phylogenetic divide between bacteria and archaea. Moreover, Plasmodium GatA also appears to have emerged prior to the bacterial-archaeal phylogenetic divide. Thus, although GatAB is found in Plasmodium, it emerged prior to the phylogenetic separation of archaea and bacteria.

Plasmodium Apicoplast Gln-tRNA Gln Biosynthesis Utilizes a Unique GatAB Amidotransferase Essential for Erythrocytic Stage Parasites

KAUST Repository

Mailu, Boniface M.

2015-08-28

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. The malaria parasite Plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-tRNA synthetase to synthesize Glu-tRNAGln and a glutaminyl-tRNA amidotransferase to convert Glu-tRNAGln to Gln-tRNAGln. Here, we show that Plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyltRNA amidotransferase consisting of GatA and GatB subunits (GatAB). We localized the P. falciparum GatA and GatB subunits to the apicoplast in blood stage parasites and demonstrated that recombinant GatAB converts Glu-tRNAGln to Gln-tRNAGln in vitro. We demonstrate that the apicoplast GatAB-catalyzed reaction is essential to the parasite blood stages because we could not delete the Plasmodium berghei gene encoding GatA in blood stage parasites in vivo. A phylogenetic analysis placed the split between Plasmodium GatB, archaeal GatE, and bacterial GatB prior to the phylogenetic divide between bacteria and archaea. Moreover, Plasmodium GatA also appears to have emerged prior to the bacterial-archaeal phylogenetic divide. Thus, although GatAB is found in Plasmodium, it emerged prior to the phylogenetic separation of archaea and bacteria.

Three-dimensional visualisation of developmental stages of an apicomplexan fish blood parasite in its invertebrate host

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Hayes Polly M

2011-11-01

Full Text Available Abstract Background Although widely used in medicine, the application of three-dimensional (3D imaging to parasitology appears limited to date. In this study, developmental stages of a marine fish haemogregarine, Haemogregarina curvata (Apicomplexa: Adeleorina, were investigated in their leech vector, Zeylanicobdella arugamensis; this involved 3D visualisation of brightfield and confocal microscopy images of histological sections through infected leech salivary gland cells. Findings 3D assessment demonstrated the morphology of the haemogregarine stages, their spatial layout, and their relationship with enlarged host cells showing reduced cellular content. Haemogregarine meronts, located marginally within leech salivary gland cells, had small tail-like connections to the host cell limiting membrane; this parasite-host cell interface was not visible in two-dimensional (2D light micrographs and no records of a similar connection in apicomplexan development have been traced. Conclusions This is likely the first account of the use of 3D visualisation to study developmental stages of an apicomplexan parasite in its invertebrate vector. Elucidation of the extent of development of the haemogregarine within the leech salivary cells, together with the unusual connections between meronts and the host cell membrane, illustrates the future potential of 3D visualisation in parasite-vector biology.

Changes in lipid composition during sexual development of the malaria parasite Plasmodium falciparum.

Science.gov (United States)

Tran, Phuong N; Brown, Simon H J; Rug, Melanie; Ridgway, Melanie C; Mitchell, Todd W; Maier, Alexander G

2016-02-06

The development of differentiated sexual stages (gametocytes) within human red blood cells is essential for the propagation of the malaria parasite, since only mature gametocytes will survive in the mosquito's midgut. Hence gametocytogenesis is a pre-requisite for transmission of the disease. Physiological changes involved in sexual differentiation are still enigmatic. In particular the lipid metabolism-despite being central to cellular regulation and development-is not well explored. Here the lipid profiles of red blood cells infected with the five different sexual stages of Plasmodium falciparum were analysed by mass spectrometry and compared to those from uninfected and asexual trophozoite infected erythrocytes. Fundamental differences between erythrocytes infected with the different parasite stages were revealed. In mature gametocytes many lipids that decrease in the trophozoite and early gametocyte infected red blood cells are regained. In particular, regulators of membrane fluidity, cholesterol and sphingomyelin, increased significantly during gametocyte maturation. Neutral lipids (serving mainly as caloriometric reserves) increased from 3 % of total lipids in uninfected to 27 % in stage V gametocyte infected red blood cells. The major membrane lipid class (phospholipids) decreased during gametocyte development. The lipid profiles of infected erythrocytes are characteristic for the particular parasite life cycle and maturity stages of gametocytes. The obtained lipid profiles are crucial in revealing the lipid metabolism of malaria parasites and identifying targets to interfere with this deadly disease.

The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.

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Pérez-Torres, Armando; Vera-Aguilera, Jesús; Hernaiz-Leonardo, Juan Carlos; Moreno-Aguilera, Eduardo; Monteverde-Suarez, Diego; Vera-Aguilera, Carlos; Estrada-Bárcenas, Daniel

2013-11-01

The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal. C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 μg/100 μL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 μL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C). The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (pcancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.

Juvenile survival in a tropical population of roseate terns: Interannual variation and effect of tick parasitism

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Monticelli, David; Ramos, Jaime A.; Hines, James E.; Nichols, James D.; Spendelow, Jeffrey A.

2008-01-01

Many demographic studies on long-lived seabirds have focused on the estimation of adult survival, but much less is known about survival during the early years of life, especially in tropical species. We report analyses of a capture–recapture dataset of 685 roseate terns ringed as fledglings and adults between 1998 and 2005 on Aride Island, Seychelles, and recaptured/resighted at the same colony site over a 5 yr (2002 to 2006) period. A multistate model was used to estimate survival for different age classes, including juvenile (first-year) birds returning as non-breeding prospectors. The effect of infestation by parasites (ticks) on survival was also examined. Overall, the estimated return of first-year individuals to the natal colony was very variable, ranging from 2 to 22%. Conditioned on survival, the probability of returning from Age 2 yr onwards increased to 70%. Survival rates were best modeled as time-specific, with estimates varying from 0.02 to 1.00 (mean 0.69) in first-year birds with a marked negative effect of tick infestation. In older birds (minimum age of 2 yr), the annual estimates fell between 0.69 and 0.86 (mean 0.77). Using a components of variance approach for estimation of year-to-year variation, we found high temporal variability for first-year individuals (coefficient of variation [CV] = 65%) compared to much less variation in the survival rate of older birds (CV = 9%). These findings agree with the life-history prediction that demographic rates of juveniles are usually lower and more variable than those of older individuals. Our results are also consistent with the predicted negative effect of tick parasitism on juvenile survival. Compared with data from other roseate tern populations, survival over the first 2 yr (Age 0 to 2 yr) was 18 to 40% higher in this study, suggesting that a high ‘young’ survival rate may be an important demographic trait in this tropical population to compensate for the low annual reproductive success. Our

Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Survival and Infectivity.

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Faria, Joana; Loureiro, Inês; Santarém, Nuno; Macedo-Ribeiro, Sandra; Tavares, Joana; Cordeiro-da-Silva, Anabela

2016-01-01

A growing interest in asparagine (Asn) metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS) is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in humans and present in trypanosomatids, AS-A was worthy of exploring as a potential drug target candidate. Appealingly, it was reported that AS-A was essential in Leishmania donovani, making it a promising drug target. In the work herein we demonstrate that Leishmania infantum AS-A, similarly to Trypanosoma spp. and L. donovani, is able to use both ammonia and glutamine as nitrogen donors. Moreover, we have successfully generated LiASA null mutants by targeted gene replacement in L. infantum, and these parasites do not display any significant growth or infectivity defect. Indeed, a severe impairment of in vitro growth was only observed when null mutants were cultured in asparagine limiting conditions. Altogether our results demonstrate that despite being important under asparagine limitation, LiAS-A is not essential for parasite survival, growth or infectivity in normal in vitro and in vivo conditions. Therefore we exclude AS-A as a suitable drug target against L. infantum parasites.

Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Survival and Infectivity.

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Joana Faria

2016-01-01

Full Text Available A growing interest in asparagine (Asn metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in humans and present in trypanosomatids, AS-A was worthy of exploring as a potential drug target candidate. Appealingly, it was reported that AS-A was essential in Leishmania donovani, making it a promising drug target. In the work herein we demonstrate that Leishmania infantum AS-A, similarly to Trypanosoma spp. and L. donovani, is able to use both ammonia and glutamine as nitrogen donors. Moreover, we have successfully generated LiASA null mutants by targeted gene replacement in L. infantum, and these parasites do not display any significant growth or infectivity defect. Indeed, a severe impairment of in vitro growth was only observed when null mutants were cultured in asparagine limiting conditions. Altogether our results demonstrate that despite being important under asparagine limitation, LiAS-A is not essential for parasite survival, growth or infectivity in normal in vitro and in vivo conditions. Therefore we exclude AS-A as a suitable drug target against L. infantum parasites.

The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites

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Charnaud, Sarah C.; Dixon, Matthew W. A.; Nie, Catherine Q.; Chappell, Lia; Sanders, Paul R.; Nebl, Thomas; Hanssen, Eric; Berriman, Matthew; Chan, Jo-Anne; Blanch, Adam J.; Beeson, James G.; Rayner, Julian C.; Przyborski, Jude M.; Tilley, Leann; Crabb, Brendan S.

2017-01-01

Malaria is caused by five different Plasmodium spp. in humans each of which modifies the host erythrocyte to survive and replicate. The two main causes of malaria, P. falciparum and P. vivax, differ in their ability to cause severe disease, mainly due to differences in the cytoadhesion of infected erythrocytes (IE) in the microvasculature. Cytoadhesion of P. falciparum in the brain leads to a large number of deaths each year and is a consequence of exported parasite proteins, some of which modify the erythrocyte cytoskeleton while others such as PfEMP1 project onto the erythrocyte surface where they bind to endothelial cells. Here we investigate the effects of knocking out an exported Hsp70-type chaperone termed Hsp70-x that is present in P. falciparum but not P. vivax. Although the growth of Δhsp70-x parasites was unaffected, the export of PfEMP1 cytoadherence proteins was delayed and Δhsp70-x IE had reduced adhesion. The Δhsp70-x IE were also more rigid than wild-type controls indicating changes in the way the parasites modified their host erythrocyte. To investigate the cause of this, transcriptional and translational changes in exported and chaperone proteins were monitored and some changes were observed. We propose that PfHsp70-x is not essential for survival in vitro, but may be required for the efficient export and functioning of some P. falciparum exported proteins. PMID:28732045

The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites.

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Sarah C Charnaud

Full Text Available Malaria is caused by five different Plasmodium spp. in humans each of which modifies the host erythrocyte to survive and replicate. The two main causes of malaria, P. falciparum and P. vivax, differ in their ability to cause severe disease, mainly due to differences in the cytoadhesion of infected erythrocytes (IE in the microvasculature. Cytoadhesion of P. falciparum in the brain leads to a large number of deaths each year and is a consequence of exported parasite proteins, some of which modify the erythrocyte cytoskeleton while others such as PfEMP1 project onto the erythrocyte surface where they bind to endothelial cells. Here we investigate the effects of knocking out an exported Hsp70-type chaperone termed Hsp70-x that is present in P. falciparum but not P. vivax. Although the growth of Δhsp70-x parasites was unaffected, the export of PfEMP1 cytoadherence proteins was delayed and Δhsp70-x IE had reduced adhesion. The Δhsp70-x IE were also more rigid than wild-type controls indicating changes in the way the parasites modified their host erythrocyte. To investigate the cause of this, transcriptional and translational changes in exported and chaperone proteins were monitored and some changes were observed. We propose that PfHsp70-x is not essential for survival in vitro, but may be required for the efficient export and functioning of some P. falciparum exported proteins.

Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

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Bingham, Brian [Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee (United States); Orton, Andrew; Boothe, Dustin [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Stoddard, Greg [Division of Epidemiology, University of Utah, Salt Lake City, Utah (United States); Huang, Y. Jessica; Gaffney, David K. [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Poppe, Matthew M., E-mail: Matthew.poppe@hci.utah.edu [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States)

2017-04-01

Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

International Nuclear Information System (INIS)

Bingham, Brian; Orton, Andrew; Boothe, Dustin; Stoddard, Greg; Huang, Y. Jessica; Gaffney, David K.; Poppe, Matthew M.

2017-01-01

Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role In the Development of Liver Stage Malarial Parasites

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Yu, Min; Santha Kumar, T. R.; Nkrumah, Louis J.; Coppi, Alida; Retzlaff, Silke; Li, Celeste D.; Kelly, Brendan J.; Moura, Pedro A.; Lakshmanan, Viswanathan; Freundlich, Joel S.; Valderramos, Juan-Carlos; Vilcheze, Catherine; Siedner, Mark; Tsai, Jennifer H.-C.; Falkard, Brie; Sidhu, Amar bir Singh; Purcell, Lisa A.; Gratraud, Paul; Kremer, Laurent; Waters, Andy P.; Schiehser, Guy; Jacobus, David P.; Janse, Chris J.; Ager, Arba; Jacobs, William R.; Sacchettini, James C.; Heussler, Volker; Sinnis, Photini; Fidock, David A.

2008-01-01

SUMMARY Fatty acid biosynthesis has been viewed as an important biological function of and therapeutic target for Plasmodium falciparum asexual blood stage infection. This apicoplast-resident type II pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of the bacterial FabI inhibitor triclosan. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood stage growth. In contrast, mosquito-derived fabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver stage development in vitro. This is characterized by an inability to form intra-hepatic merosomes that normally initiate blood stage infections. These data illuminate key differences between liver and blood stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions. PMID:19064257

The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.

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Yu, Min; Kumar, T R Santha; Nkrumah, Louis J; Coppi, Alida; Retzlaff, Silke; Li, Celeste D; Kelly, Brendan J; Moura, Pedro A; Lakshmanan, Viswanathan; Freundlich, Joel S; Valderramos, Juan-Carlos; Vilcheze, Catherine; Siedner, Mark; Tsai, Jennifer H-C; Falkard, Brie; Sidhu, Amar Bir Singh; Purcell, Lisa A; Gratraud, Paul; Kremer, Laurent; Waters, Andrew P; Schiehser, Guy; Jacobus, David P; Janse, Chris J; Ager, Arba; Jacobs, William R; Sacchettini, James C; Heussler, Volker; Sinnis, Photini; Fidock, David A

2008-12-11

The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in Plasmodium falciparum asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial FabI. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver-stage development in vitro. This defect is characterized by an inability to form intrahepatic merosomes that normally initiate blood-stage infections. These data illuminate key differences between liver- and blood-stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions.

Is low survival for cancer in Eastern Europe due principally to late stage at diagnosis?

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Minicozzi, Pamela; Walsh, Paul M; Sánchez, Maria-José; Trama, Annalisa; Innos, Kaire; Marcos-Gragera, Rafael; Dimitrova, Nadya; Botta, Laura; Johannesen, Tom B; Rossi, Silvia; Sant, Milena

2018-04-01

Cancer survival has persistently been shown to be worse for Eastern European and UK/Ireland patients than those of other European regions. This is often attributed to later stage at diagnosis. However, few stage-specific survival comparisons are available, so it is unclear whether poorer quality treatment or other factors also contribute. For the first time, European cancer registries have provided stage-at-diagnosis data to EUROCARE, enabling population-based stage-specific survival estimates across Europe. In this retrospective observational study, stage at diagnosis (as TNM, condensed TNM, or Extent of Disease) was analysed for patients (≥15 years) from 15 countries grouped into 4 regions (Northern Europe: Norway; Central Europe: Austria, France, Germany, Switzerland, The Netherlands; Southern Europe: Croatia, Italy, Slovenia, and Spain; and Eastern Europe: Bulgaria, Estonia, Lithuania, Poland, and Slovakia), diagnosed with 7 malignant cancers in 2000-2007, and followed to end of 2008. A new variable (reconstructed stage) was created which used all available stage information. Age-standardised 5-year relative survival (RS) by reconstructed stage was estimated and compared between regions. Excess risks of cancer death in the 5 years after diagnosis were also estimated, taking age, sex and stage into account. Low proportions of Eastern European patients were diagnosed with local stage cancers and high proportions with metastatic stage cancers. Stage-specific RS (especially for non-metastatic disease) was generally lower for Eastern European patients. After adjusting for age, sex, and stage, excess risks of death remained higher for Eastern European patients than for European patients in general. Late diagnosis alone does not explain worse cancer survival in Eastern Europe: greater risk of cancer death together with worse stage-specific survival suggest less effective care, probably in part because fewer resources are allocated to health care than in the rest of

The Cytoplasmic Prolyl-tRNA Synthetase of the Malaria Parasite is a Dual-Stage Target for Drug Development

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Herman, Jonathan D.; Pepper, Lauren R.; Cortese, Joseph F.; Estiu, Guillermina; Galinsky, Kevin; Zuzarte-Luis, Vanessa; Derbyshire, Emily R.; Ribacke, Ulf; Lukens, Amanda K.; Santos, Sofia A.; Patel, Vishal; Clish, Clary B.; Sullivan, William J.; Zhou, Huihao; Bopp, Selina E.; Schimmel, Paul; Lindquist, Susan; Clardy, Jon; Mota, Maria M.; Keller, Tracy L.; Whitman, Malcolm; Wiest, Olaf; Wirth, Dyann F.; Mazitschek, Ralph

2015-01-01

The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for the development of the next-generation of antimalarial drugs. Using an integrated chemogenomics approach that combined drug-resistance selection, whole genome sequencing and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivatives such as halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the P. berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is highly active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses, and represents a promising lead for the development of dual-stage next generation antimalarials. PMID:25995223

The role of radiation therapy for stage IIIB non-small cell lung cancer. Impact of clinical nodal stage on survival

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Hayakawa, Kazushige; Mitsuhashi, Norio; Furuta, Masaya; Saito, Yoshihiro; Nakayama, Yuko; Katano, Susumu; Ohno, Tatsuya; Niibe, Hideo

1996-01-01

From 1976 through 1989, 46 patients with stage IIIB non-small cell lung cancer (NSCLC) without malignant effusion were treated with definitive radiation therapy (RT) at Gunma University Hospital. All patients were treated with 10 MV x-rays using antero posterior parallel opposed fields. The total dose ranged from 60 Gy to 70 Gy (mean dose; 66 Gy) with once daily standard fractionation. The actuarial two and five-year survival rates of the entire group were 22% and 10% respectively with a median survival time (MST) of 10 months. The survival of 18 patients with stage N0-2 disease was significantly better than the 28 patients with stage N3 disease (MST 21 versus 9 months; p<0.05). There were no significant differences in survival based on age and sex. However, there was a borderline difference in survival rates between patients with a performance status of 0-1 and those with status of 2-3 (p=0.06). Three patients with squamous cell carcinoma were alive after 5 years and were without disease progression. No patients with non-squamous cell carcinoma were free of disease after 5 years. These results provide support for the use of definitive RT to manage those patients with limited stage IIIB squamous cell carcinoma not extending to N3 stage. (author)

The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum.

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Robbins, Jonathan A; Absalon, Sabrina; Streva, Vincent A; Dvorin, Jeffrey D

2017-06-13

All well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs), and these protein kinase complexes are viable drug targets. The regulatory control of the Plasmodium falciparum cell division cycle remains poorly understood, and the roles of the various CDKs and cyclins remain unclear. The P. falciparum genome contains multiple CDKs, but surprisingly, it does not contain any sequence-identifiable G 1 -, S-, or M-phase cyclins. We demonstrate that P. falciparum Cyc1 (PfCyc1) complements a G 1 cyclin-depleted Saccharomyces cerevisiae strain and confirm that other identified malaria parasite cyclins do not complement this strain. PfCyc1, which has the highest sequence similarity to the conserved cyclin H, cannot complement a temperature-sensitive yeast cyclin H mutant. Coimmunoprecipitation of PfCyc1 from P. falciparum parasites identifies PfMAT1 and PfMRK as specific interaction partners and does not identify PfPK5 or other CDKs. We then generate an endogenous conditional allele of PfCyc1 in blood-stage P. falciparum using a destabilization domain (DD) approach and find that PfCyc1 is essential for blood-stage proliferation. PfCyc1 knockdown does not impede nuclear division, but it prevents proper cytokinesis. Thus, we demonstrate that PfCyc1 has a functional divergence from bioinformatic predictions, suggesting that the malaria parasite cell division cycle has evolved to use evolutionarily conserved proteins in functionally novel ways. IMPORTANCE Human infection by the eukaryotic parasite Plasmodium falciparum causes malaria. Most well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs) to promote essential cell division processes. Remarkably, there are no identifiable cyclins that are predicted to control the cell cycle in the malaria parasite genome. Thus, our knowledge regarding the basic mechanisms of the malaria parasite cell cycle remains unsatisfactory. We

Melanoma survival is superior in females across all tumour stages but is influenced by age.

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Khosrotehrani, Kiarash; Dasgupta, Paramita; Byrom, Lisa; Youlden, Danny R; Baade, Peter D; Green, Adele C

2015-10-01

Among patients with invasive melanoma, females are known to have higher survival than males globally. However, this survival advantage has not been explored in thin melanomas, the most common form of the disease. In addition, it is unclear if this advantage is true across all age groups. We aimed to compare melanoma survival between males and females by clinical stage and within age groups. Melanomas from 1995 to 2008 were extracted from the Queensland Cancer Registry and the Surveillance, Epidemiology, and End Results (SEER) Program, and melanoma-specific deaths were ascertained up to 2011. Flexible parametric survival models compared survival between groups. The Queensland cohort of 28,979 patients experienced 1712 melanoma deaths and the SEER cohort of 57,402 patients included 6929 melanoma deaths. Survival rates were in favour of females across nearly all tumour stages, including thin invasive tumours in both cohorts after adjusting for demographic and clinical factors [odds ratio (OR) death female:male for stage I melanoma = 0.64 in Queensland; and OR = 0.79 in the US, both P age categories. In particular, the survival advantage was inconsistent in females with stage I melanoma aged under 60. Females with melanoma have a survival advantage over males including in stage I melanomas. However, this advantage is dependent on age at diagnosis, suggesting an underlying biological mechanism influenced by age that exists from the very early stages of the disease.

Malaria parasites: the great escape

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Laurent Rénia

2016-11-01

Full Text Available Parasites of the genus Plasmodium have a complex life cycle. They alternate between their final mosquito host and their intermediate hosts. The parasite can be either extra- or intracellular, depending on the stage of development. By modifying their shape, motility, and metabolic requirements, the parasite adapts to the different environments in their different hosts. The parasite has evolved to escape the multiple immune mechanisms in the host that try to block parasite development at the different stages of their development. In this article, we describe the mechanisms reported thus far that allow the Plasmodium parasite to evade innate and adaptive immune responses.

Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

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Gazzinelli R.T.

1998-01-01

Full Text Available Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host. Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

Energetic cost of bot fly parasitism in free-ranging eastern chipmunks.

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Careau, Vincent; Thomas, Donald W; Humphries, Murray M

2010-02-01

The energy and nutrient demands of parasites on their hosts are frequently invoked as an explanation for negative impacts of parasitism on host survival and reproductive success. Although cuterebrid bot flies are among the physically largest and most-studied insect parasites of mammals, the only study conducted on metabolic consequences of bot fly parasitism revealed a surprisingly small effect of bot flies on host metabolism. Here we test the prediction that bot fly parasitism increases the resting metabolic rate (RMR) of free-ranging eastern chipmunks (Tamias striatus), particularly in juveniles who have not previously encountered parasites and have to allocate energy to growth. We found no effect of bot fly parasitism on adults. In juveniles, however, we found that RMR strongly increased with the number of bot fly larvae hosted. For a subset of 12 juveniles during a year where parasite prevalence was particularly high, we also compared the RMR before versus during the peak of bot fly prevalence, allowing each individual to act as its own control. Each bot fly larva resulted in a approximately 7.6% increase in the RMR of its host while reducing juvenile growth rates. Finally, bot fly parasitism at the juvenile stage was positively correlated with adult stage RMR, suggesting persistent effects of bot flies on RMR. This study is the first to show an important effect of bot fly parasitism on the metabolism and growth of a wild mammal. Our work highlights the importance of studying cost of parasitism over multiple years in natural settings, as negative effects on hosts are more likely to emerge in periods of high energetic demand (e.g. growing juveniles) and/or in harsh environmental conditions (e.g. low food availability).

Asexual populations of the human malaria parasite, Plasmodium falciparum, use a two-step genomic strategy to acquire accurate, beneficial DNA amplifications.

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Jennifer L Guler

Full Text Available Malaria drug resistance contributes to up to a million annual deaths. Judicious deployment of new antimalarials and vaccines could benefit from an understanding of early molecular events that promote the evolution of parasites. Continuous in vitro challenge of Plasmodium falciparum parasites with a novel dihydroorotate dehydrogenase (DHODH inhibitor reproducibly selected for resistant parasites. Genome-wide analysis of independently-derived resistant clones revealed a two-step strategy to evolutionary success. Some haploid blood-stage parasites first survive antimalarial pressure through fortuitous DNA duplications that always included the DHODH gene. Independently-selected parasites had different sized amplification units but they were always flanked by distant A/T tracks. Higher level amplification and resistance was attained using a second, more efficient and more accurate, mechanism for head-to-tail expansion of the founder unit. This second homology-based process could faithfully tune DNA copy numbers in either direction, always retaining the unique DNA amplification sequence from the original A/T-mediated duplication for that parasite line. Pseudo-polyploidy at relevant genomic loci sets the stage for gaining additional mutations at the locus of interest. Overall, we reveal a population-based genomic strategy for mutagenesis that operates in human stages of P. falciparum to efficiently yield resistance-causing genetic changes at the correct locus in a successful parasite. Importantly, these founding events arise with precision; no other new amplifications are seen in the resistant haploid blood stage parasite. This minimizes the need for meiotic genetic cleansing that can only occur in sexual stage development of the parasite in mosquitoes.

Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes.

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Ingrid Rossouw

2015-05-01

Full Text Available Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries.

Colorectal cancers detected through screening are associated with lower stages and improved survival

DEFF Research Database (Denmark)

Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

2014-01-01

in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival. MATERIAL AND METHODS: All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences...... in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers...... detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...

A survival-reproduction trade-off in entomopathogenic nematodes mediated by their bacterial symbionts.

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Emelianoff, Vanya; Chapuis, Elodie; Le Brun, Nathalie; Chiral, Magali; Moulia, Catherine; Ferdy, Jean-Baptiste

2008-04-01

In this work, we investigate the investment of entomopathogenic Steinernema nematodes (Rhabditidae) in their symbiotic association with Xenorhabdus bacteria (Enterobacteriaceae). Their life cycle comprises two phases: (1) a free stage in the soil, where infective juveniles (IJs) of the nematode carry bacteria in a digestive vesicle and search for insect hosts, and (2) a parasitic stage into the insect where bacterial multiplication, nematode reproduction, and production of new IJs occur. Previous studies clearly showed benefits to the association for the nematode during the parasitic stage, but preliminary data suggest the existence of costs to the association for the nematode in free stage. IJs deprived from their bacteria indeed survive longer than symbiotic ones. Here we show that those bacteria-linked costs and benefits lead to a trade-off between fitness traits of the symbiotic nematodes. Indeed IJs mortality positively correlates with their parasitic success in the insect host for symbiotic IJs and not for aposymbiotic ones. Moreover mortality and parasitic success both positively correlate with the number of bacteria carried per IJ, indicating that the trade-off is induced by symbiosis. Finally, the trade-off intensity depends on parental effects and, more generally, is greater under restrictive environmental conditions.

Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

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Karina Mastropasqua Rebello

2012-09-01

Full Text Available Angiostrongylus costaricensis is a nematode that causes abdominal angiostrongyliasis, a widespread human parasitism in Latin America. This study aimed to characterize the protease profiles of different developmental stages of this helminth. First-stage larvae (L1 were obtained from the faeces of infected Sigmodon hispidus rodents and third-stage larvae (L3 were collected from mollusks Biomphalaria glabrata previously infected with L1. Adult worms were recovered from rodent mesenteric arteries. Protein extraction was performed after repeated freeze-thaw cycles followed by maceration of the nematodes in 40 mM Tris base. Proteolysis of gelatin was observed by zymography and found only in the larval stages. In L3, the gelatinolytic activity was effectively inhibited by orthophenanthroline, indicating the involvement of metalloproteases. The mechanistic class of the gelatinases from L1 could not be precisely determined using traditional class-specific inhibitors. Adult worm extracts were able to hydrolyze haemoglobin in solution, although no activity was observed by zymography. This haemoglobinolytic activity was ascribed to aspartic proteases following its effective inhibition by pepstatin, which also inhibited the haemoglobinolytic activity of L1 and L3 extracts. The characterization of protease expression throughout the A. costaricensis life cycle may reveal key factors influencing the process of parasitic infection and thus foster our understanding of the disease pathogenesis.

Parasitology: Parasite survives predation on its host

DEFF Research Database (Denmark)

Ponton, Fleur; Lebarbenchon, Camille; Lefèvre, Thierry

2006-01-01

As prisoners in their living habitat, parasites should be vulnerable to destruction by the predators of their hosts. But we show here that the parasitic gordian worm Paragordius tricuspidatus is able to escape not only from its insect host after ingestion by a fish or frog but also from...

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

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Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Declining Brown-headed Cowbird (Molothrus ater populations are associated with landscape-specific reductions in brood parasitism and increases in songbird productivity.

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W Andrew Cox

Full Text Available Many songbird species have experienced significant population declines, partly because of brood parasitism by the Brown-headed Cowbird (Molothrus ater, which is positively associated with increasing landscape forest cover in the midwestern United States. However, cowbirds are also experiencing long-term population declines, which should reduce parasitism pressure and thus increase productivity of host species. We used 20 years of nest monitoring data from five sites in Missouri across a gradient of landscape forest cover to assess temporal trends in the rate and intensity of brood parasitism for Acadian Flycatchers (Empidonax virescens, Indigo Buntings (Passerina cyanea, and Northern Cardinals (Cardinalis cardinalis. We evaluated whether there were concomitant changes in fledging brood size, nest survival, a combination of the two metrics (i.e., host young produced per nest attempt, and whether such changes were more substantial with decreasing landscape forest cover. Parasitism rates and intensities declined substantially during 1991-2010. Fledging brood size and nest survival rates were positively associated with landscape forest cover, confirming the fragmentation hypothesis for Midwest forest birds. Declining parasitism rates were associated with increased fledging brood sizes, with more pronounced increases as landscape forest cover decreased. Nest survival increased insubstantially across time during laying and incubation, but not during the nestling stage. The best predictor of nest survival was parasitism status, with parasitized nests surviving at lower rates than unparasitized nests. Overall, productivity increased during 1991-2010, with more pronounced increases associated with lower levels of landscape forest cover. The negative effects of cowbirds on nest survival in addition to fledging brood size in less forested landscapes suggest that cowbirds may be a primary cause of forest fragmentation effects on songbird productivity in the

A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity.

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Géraldine De Muylder

2013-10-01

Full Text Available In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.

Survival impact of early lymph node staging in a national study on 454 Danish men with penile cancer

DEFF Research Database (Denmark)

Jakobsen, J. K.; Krarup, K. P.; Sommer, P.

2015-01-01

N) stage so extranodal metastatic extension entails stage pN3. We report population based national survival data from 454 Danish penile cancer patients staged according to the TNM 2009 criteria and evaluate the survival impact of lymph node staging at diagnosis. MATERIAL & METHODS: Penile squamous cell...... intervals. Survival impact of lymph node staging was evaluated in a multivariate cox regression model with adjustment for tumour stage, age and Charlson comorbidity score. RESULTS: Of a total of 454 men 39 did not undergo lymph node staging of any kind. Median follow-up of patients who survived was 7......-45) %. Penile cancer-specific 5-year survival for pN0, pN1, pN2, pN3 and pNx patients was 97 (94-98)%, 82 (62- 92)%, 57 (36-74)%, 12 (5-22)% and 53 (35-69)%. Lymph node staging had a significant impact on penile cancer specific survival after adjustment for age, T-stage and comorbidity (Nx vs all N0, N1, N2, N3...

Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products.

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Yovany Moreno

Full Text Available INTRODUCTION: While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection. METHODOLOGY/PRINCIPAL FINDINGS: To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP. CONCLUSIONS/SIGNIFICANCE: A comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host-parasite interaction.

Men and women show similar survival outcome in stage IV breast cancer.

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Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

2017-08-01

To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of temperature on different stages of Romanomermis iyengari, a mermithid nematode parasite of mosquitoes

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K. P. Paily

1994-12-01

Full Text Available The effect of temperature (20 degrees-35 degrees C on different stages of Romanomermis iyengari was studied. In embryonic development, the single-cell stage eggs developed into mature eggs in 4.5-6.5 days at 25-35 degrees C but, required 9.5 days at 20 degrees C. Complete hatching occurred in 7 and 9 days after egg-laying at 35 and 30 degrees C, respectively. At 25 and 20 degrees C, 85-96 of the eggs did not hatch even by 30th day. Loss of infectivity and death of the preparasites occurred faster at higher temperatures. The 50 survival durations of preparasites at 20 and 35 degrees C were 105.8 and 10.6 hr respectively. They retained 50 infectivity up to 69.7 and 30.3 hr. The duration of the parasitic phase increased as temperature decreased. Low temperature favoured production of a higher proportion of females which were also larger in size. The maximum time taken for the juveniles to become adults was 14 days at 20 degrees C and the minimum was 9 days at 35 degrees C. Oviposition began earlier at higher temperature than at lower temperature. However, its fecundic period was shorter at 20 degrees C than at 35 degrees C indicating enhanced rate of oviposition at 20 degrees C. Fecundity was adversely affected at 20 degrees C and 35 degrees C. It is shown that the temperature range of 25 degrees-30 degrees C favours optimum development of R. iyengari.

Disentangling the influence of parasite genotype, host genotype and maternal environment on different stages of bacterial infection in Daphnia magna.

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Hall, Matthew D; Ebert, Dieter

2012-08-22

Individuals naturally vary in the severity of infectious disease when exposed to a parasite. Dissecting this variation into genetic and environmental components can reveal whether or not this variation depends on the host genotype, parasite genotype or a range of environmental conditions. Complicating this task, however, is that the symptoms of disease result from the combined effect of a series of events, from the initial encounter between a host and parasite, through to the activation of the host immune system and the exploitation of host resources. Here, we use the crustacean Daphnia magna and its parasite Pasteuria ramosa to show how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease. Using compatible host-parasite combinations, we experimentally exclude variation in the ability of a parasite to penetrate the host, from measures of parasite clearance, the reduction in host fecundity and the proliferation of the parasite. We show how parasite resistance consists of two components that vary in environmental sensitivity, how the maternal environment influences all measured aspects of the within-host infection process and how host-parasite interactions following the penetration of the parasite into the host have a distinct temporal component.

Seasonal and demographic factors influencing gastrointestinal parasitism in ungulates of Etosha National Park.

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Turner, Wendy C; Getz, Wayne M

2010-10-01

Host-parasite dynamics can be strongly affected by seasonality and age-related host immune responses. We investigated how observed variation in the prevalence and intensity of parasite egg or oocyst shedding in four co-occurring ungulate species may reflect underlying seasonal variation in transmission and host immunity. This study was conducted July 2005-October 2006 in Etosha National Park, Namibia, using indices of parasitism recorded from 1,022 fecal samples collected from plains zebra (Equus quagga), springbok (Antidorcas marsupialis), blue wildebeest (Connochaetes taurinus), and gemsbok (Oryx gazella). The presence and intensity of strongyle nematodes, Strongyloides spp. and Eimeria spp. parasites, were strongly seasonal for most host-parasite combinations, with more hosts infected in the wet season than the dry season. Strongyle intensity in zebra was significantly lower in juveniles than adults, and in springbok hosts, Eimeria spp. intensity was significantly greater in juveniles than adults. These results provide evidence that acquired immunity is less protective against strongyle nematodes than Eimeria spp. infections. The seasonal patterns in parasitism further indicate that the long dry season may limit development and survival of parasite stages in the environment and, as a result, host contact and parasite transmission.

Longitudinal study of parasite-induced mortality of a long-lived host: the importance of exposure to non-parasitic stressors.

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Chin, Hilary M-H; Luong, Lien T; Shostak, Allen W

2017-12-01

Hosts face mortality from parasitic and environmental stressors, but interactions of parasitism with other stressors are not well understood, particularly for long-lived hosts. We monitored survival of flour beetles (Tribolium confusum) in a longitudinal design incorporating cestode (Hymenolepis diminuta) infection, starvation and exposure to the pesticide diatomaceous earth (DE). We found that cestode cysticercoids exhibit increasing morphological damage and decreasing ability to excyst over time, but were never eliminated from the host. In the presence of even mild environmental stressors, host lifespan was reduced sufficiently that extensive degradation of cysticercoids was never realized. Median host lifespan was 200 days in the absence of stressors, and 3-197 days with parasitism, starvation and/or DE. Early survival of parasitized hosts was higher relative to controls in the presence of intermediate concentrations of DE, but reduced under all other conditions tested. Parasitism increased host mortality in the presence of other stressors at times when parasitism alone did not cause mortality, consistent with an interpretation of synergy. Environmental stressors modified the parasite numbers needed to reveal intensity-dependent host mortality, but only rarely masked intensity dependence. The longitudinal approach produced observations that would have been overlooked or misinterpreted if survival had only been monitored at a single time point.

Contamination of public squares and parks with parasites in Erbil city, Iraq

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Khder Nooraldeen

2015-09-01

Full Text Available Introduction and objective. The soil of public squares and parks may be contaminated with the infective stages of parasites because of the presence of stray animals in these parks. Many people take a rest in these places and they may be at risk of infection with parasites because the infective stages of parasites can survive for months, or even years, in spite of the factors of weather. Objective. To evaluate contamination with the eggs of parasites in the soil of parks in Erbil city, Iraq. Material and methods. Forty-eight soil samples were collected from 12 public parks and gardens from 11 different neighbourhoods (8 parks and 3 playgrounds and one district in Erbil city. The zinc sulfate floatation method was used to recover the eggs of parasites from the samples. Results. Eggs of parasites were identified in 91.6% of the parks. Eggs of [i]Hymenolepis diminuta[/i] were found in 75%, [i]Toxocara [/i]spp. in 50%, [i]Ascaris[/i] spp. in 33.3%, [i]Taenia[/i] spp. in 25%, hookworm in 25%, [i]Trichostrongylus[/i] spp. in 16.7% and Trichuris spp. in 16.7% of the parks. [i]Helminth[/i] eggs were found in 48% soil samples with a mean number of 1.1 per soil sample. The most contaminated soil sample was found in a park in neighbourhood number 325 with 6 eggs. Conclusions. The presence of pathogenic parasites in the soil of parks in Erbil city constitutes a high risk to the people who use these parks for recreation, and requires the appropriate control for these parasites.

Effects of Ichthyophthirius multifiliis parasitism on the survival, hematology and bacterial load in channel catfish previously exposed to Edwardsiella ictaluri

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The effect of Ichthyophthirius multifiliis (Ich) parasitism on survival, hematology and bacterial load in channel catfish, Ictalurus punctatus, previously exposed to Edwardsiella ictaluri was studied. Fish were exposed to E. ictaluri one day prior to Ich in the following treatments: 1)- infected by...

Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition

DEFF Research Database (Denmark)

Jogdand, Prajakta S; Singh, Susheel K; Christiansen, Michael

2012-01-01

asynchronous and tightly synchronized asexual blood stage cultures of Plasmodium falciparum were stained with CMXRos and subjected to detection by flow cytometry and fluorescence microscopy. The parasite counts obtained by flow cytometry were compared to standard microscopic counts obtained through examination......ABSTRACT: BACKGROUND: Functional in vitro assays could provide insights into the efficacy of malaria vaccine candidates. For estimating the anti-parasite effect induced by a vaccine candidate, an accurate determination of live parasite count is an essential component of most in vitro bioassays....... Although traditionally parasites are counted microscopically, a faster, more accurate and less subjective method for counting parasites is desirable. In this study mitochondrial dye (Mitotracker Red CMXRos) was used for obtaining reliable live parasite counts through flow cytometry. METHODS: Both...

Survival Analysis of Patients with End Stage Renal Disease

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Urrutia, J. D.; Gayo, W. S.; Bautista, L. A.; Baccay, E. B.

2015-06-01

This paper provides a survival analysis of End Stage Renal Disease (ESRD) under Kaplan-Meier Estimates and Weibull Distribution. The data were obtained from the records of V. L. MakabaliMemorial Hospital with respect to time t (patient's age), covariates such as developed secondary disease (Pulmonary Congestion and Cardiovascular Disease), gender, and the event of interest: the death of ESRD patients. Survival and hazard rates were estimated using NCSS for Weibull Distribution and SPSS for Kaplan-Meier Estimates. These lead to the same conclusion that hazard rate increases and survival rate decreases of ESRD patient diagnosed with Pulmonary Congestion, Cardiovascular Disease and both diseases with respect to time. It also shows that female patients have a greater risk of death compared to males. The probability risk was given the equation R = 1 — e-H(t) where e-H(t) is the survival function, H(t) the cumulative hazard function which was created using Cox-Regression.

Survival and Movement of Insect Parasitic Nematodes in Poultry Manure and Their Infectivity Against Musca domestica

OpenAIRE

Georgis, Ramon; Mullens, Bradley A.; Meyer, Jeffery A.

1987-01-01

Survival, infectivity, and movement of three insect parasitic nematodes (Steinernema feltiae All strain, S. bibionis SN strain, and Heterorhabditis heliothidis NC strain) in poultry manure were tested under laboratory conditions. The majority (70-100%) of the nematodes died within 18 hours after exposure to the manure. Nematodes exposed to manure slurry for 6 hours killed at least 95% of the house fly larvae, Musca domestica, but nematodes exposed for 12 hours achieved less than 40% larval mo...

Hitherto unseen survival in an ALK-positive-patient with advanced stage adult ganglioneuroblastoma treated with personalized medicine

DEFF Research Database (Denmark)

Risum, Signe; Knigge, Ulrich; Langer, Seppo W

2017-01-01

Survival of stage 4 ganglioneuroblastoma (GNB) patients is poor; no reports exist of patients surviving up to 5 years (1, 2). We report the clinical and therapeutic course of a patient with stage 4 GNB surviving beyond expectations due to a multimodal treatment approach incorporating new technolo...

Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

Science.gov (United States)

Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

2017-11-17

Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

Survival of weed seeds and animal parasites as affected by anaerobic digestion at meso- and thermophilic conditions.

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Johansen, Anders; Nielsen, Henrik B; Hansen, Christian M; Andreasen, Christian; Carlsgart, Josefine; Hauggard-Nielsen, Henrik; Roepstorff, Allan

2013-04-01

Anaerobic digestion of residual materials from animals and crops offers an opportunity to simultaneously produce bioenergy and plant fertilizers at single farms and in farm communities where input substrate materials and resulting digested residues are shared among member farms. A surplus benefit from this practice may be the suppressing of propagules from harmful biological pests like weeds and animal pathogens (e.g. parasites). In the present work, batch experiments were performed, where survival of seeds of seven species of weeds and non-embryonated eggs of the large roundworm of pigs, Ascaris suum, was assessed under conditions similar to biogas plants managed at meso- (37°C) and thermophilic (55°C) conditions. Cattle manure was used as digestion substrate and experimental units were sampled destructively over time. Regarding weed seeds, the effect of thermophilic conditions (55°C) was very clear as complete mortality, irrespective of weed species, was reached after less than 2 days. At mesophilic conditions, seeds of Avena fatua, Sinapsis arvensis, Solidago canadensis had completely lost germination ability, while Brassica napus, Fallopia convolvulus and Amzinckia micrantha still maintained low levels (~1%) of germination ability after 1 week. Chenopodium album was the only weed species which survived 1 week at substantial levels (7%) although after 11 d germination ability was totally lost. Similarly, at 55°C, no Ascaris eggs survived more than 3h of incubation. Incubation at 37°C did not affect egg survival during the first 48 h and it took up to 10 days before total elimination was reached. In general, anaerobic digestion in biogas plants seems an efficient way (thermophilic more efficient than mesophilic) to treat organic farm wastes in a way that suppresses animal parasites and weeds so that the digestates can be applied without risking spread of these pests. Copyright © 2012 Elsevier Ltd. All rights reserved.

Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite.

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Elizabeth S Zuccala

Full Text Available Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion.

A parasitism-mutualism-predation model consisting of crows, cuckoos and cats with stage-structure and maturation delays on crows and cuckoos

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Luo, Yantao; Zhang, Long; Teng, Zhidong; DeAngelis, Donald L.

2018-01-01

In this paper, a parasitism-mutualism-predation model is proposed to investigate the dynamics of multi-interactions among cuckoos, crows and cats with stage-structure and maturation time delays on cuckoos and crows. The crows permit the cuckoos to parasitize their nestlings (eggs) on the crow chicks (eggs). In return, the cuckoo nestlings produce a malodorous cloacal secretion to protect the crow chicks from predation by the cats, which is apparently beneficial to both the crow and cuckoo population. The multi-interactions, i.e., parasitism and mutualism between the cuckoos (nestlings) and crows (chicks), predation between the cats and crow chicks are modeled both by Holling-type II and Beddington-DeAngelis-type functional responses. The existence of positive equilibria of three subsystems of the model are discussed. The criteria for the global stability of the trivial equilibrium are established by the Krein-Rutman Theorem and other analysis methods. Moreover, the threshold dynamics for the coexistence and weak persistence of the model are obtained, and we show, both analytically and numerically, that the stabilities of the interior equilibria may change with the increasing maturation time delays. We find there exists an evident difference in the dynamical properties of the parasitism-mutualism-predation model based on whether or not we consider the effects of stage-structure and maturation time delays on cuckoos and crows. Inclusion of stage structure results in many varied dynamical complexities which are difficult to encompass without this inclusion.

Effects of road salt on larval amphibian susceptibility to parasitism through behavior and immunocompetence.

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Milotic, Dino; Milotic, Marin; Koprivnikar, Janet

2017-08-01

Large quantities of road salts are used for de-icing in temperate climates but often leach into aquatic ecosystems where they can cause harm to inhabitants, including reduced growth and survival. However, the implications of road salt exposure for aquatic animal susceptibility to pathogens and parasites have not yet been examined even though infectious diseases can significantly contribute to wildlife population declines. Through a field survey, we found a range of NaCl concentrations (50-560mg/L) in ponds known to contain larval amphibians, with lower levels found in sites close to gravel- rather than hard-surfaced roads. We then investigated how chronic exposure to environmentally-realistic levels of road salt (up to 1140mg/L) affected susceptibility to infection by trematode parasites (helminths) in larval stages of two amphibian species (Lithobates sylvaticus - wood frogs, and L. pipiens - northern leopard frogs) by considering effects on host anti-parasite behavior and white blood cell profiles. Wood frogs exposed to road salt had higher parasite loads, and also exhibited reduced anti-parasite behavior in these conditions. In contrast, infection intensity in northern leopard frogs had a non-monotonic response to road salts even though lymphocytes were only elevated at the highest concentration. Our results indicate the potential for chronic road salt exposure to affect larval amphibian susceptibility to pathogenic parasites through alterations of behavior and immunocompetence, with further studies needed at higher concentrations, as well as that of road salts on free-living parasite infectious stages. Copyright © 2017 Elsevier B.V. All rights reserved.

Survival significance of epidermal growth factor receptor tyrosine kinase inhibitors and current staging system for survival after recurrence in patients with completely resected lung adenocarcinoma

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Saji, Hisashi; Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Nakamura, Haruhiko

2017-01-01

Objective We previously reported that the staging system and epidermal growth factor receptor (EGFR) mutation status are key factors for treatment strategy and predicting survival. However, the significance of these factors as predictors of overall survival (OS) and postoperative recurrence survival (PRS) has not been sufficiently elucidated. The objective here was to investigate EGFR mutation status and p-stage, which affect PRS and OS in patients with completely resected lung adenocarcinoma, using a different database. Patients and methods We retrospectively reviewed 56 consecutive lung adenocarcinoma patients with disease recurrence in St. Marianna University Hospital between January 2010 and December 2014. Results EGFR mutants (M) were detected in 16/56 patients (29%). The patients with EGFR M had a better OS than those with EGFR wild-type (WT) status (5-year survival: 50.3% vs 43.1, P=0.133). There was no significant difference in the 3-year recurrence-free survival rate between patients with M and WT (6.3% vs 7.7%, P=0.656), and the patients with EGFR M had a significantly better 3-year PRS than those with WT (77.4% vs 51.7%, P=0.033). The 3-year PRS rate for patients with M/pathologic stage (p-stage) I–II (87.5%) was better than that for patients with M/p-stage III (60.0%), WT/p-stage I–II (52.7%), and WT/p-stage III (43.8%). There was a significant difference between patients with M/p-stage I and WT/p-stage I–II or WT/p-stage III (P=0.021 and 0.030, respectively). During the study period, of the 16 patients with mutants, 12 patients (75%) received EGFR-tyrosine kinase inhibitor (TKI) therapy and among the 40 patients with WT, no patient received EGFR-TKI therapy. Multivariate survival analysis showed that patients with EGFR-TKI therapy had a statistically significant association with favorable PRS (hazard ratio 0.271; 95% confidence interval 0.074–1.000; P=0.050). Conclusion EGFR status and p-stage were found to be essential prognostic factors for

Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

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Visser Otto

2010-06-01

Full Text Available Abstract Background Diagnosing colorectal cancer (CRC at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear. Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC. Methods Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B and late stage (Dukes C or D cancer. Patients were followed up for 3.5 years after diagnosis. Results In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE was 31 (1.5 weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27. In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93. In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01. In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median versus short delay (≤median was 1.8 (95% confidence interval (CI 1.1 to 3.0; p = 0.01. Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors. Conclusion In symptomatic CRC patients, a longer diagnostic and

Characteristics of juvenile survivors reveal spatio-temporal differences in early life stage survival of Baltic cod

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Huwer, Bastian; Hinrichsen, H.H.; Böttcher, U.

2014-01-01

with previous modeling studies on the survival chances of early-stage larvae and with general spatio-temporal patterns of larval prey availability suggests that differences in survival are related to food availability during the early larval stage. Results are discussed in relation to the recruitment process...

Inducible Costimulator Expressing T Cells Promote Parasitic Growth During Blood Stage Plasmodium berghei ANKA Infection

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Gajendra M. Jogdand

2018-05-01

Full Text Available The lethality of blood stage Plasmodium berghei ANKA (PbA infection is associated with the expression of T-bet and production of cytokine IFN-γ. Expression of inducible costimulator (ICOS and its downstream signaling has been shown to play a critical role in the T-bet expression and IFN-γ production. Although earlier studies have examined the role of ICOS in the control of acute blood-stage infection of Plasmodium chabaudi chabaudi AS (a non-lethal model of malaria infection, its significance in the lethal blood-stage of PbA infection remains unclear. Thus, to address the seminal role of ICOS in lethal blood-stage of PbA infection, we treated PbA-infected mice with anti-ICOS antibody and observed that these mice survived longer than their infected counterparts with significantly lower parasitemia. Anti-ICOS treatment notably depleted ICOS expressing CD4+ and CD8+ T cells with a concurrent reduction in plasma IFN-γ, which strongly indicated that ICOS expressing T cells are major IFN-γ producers. Interestingly, we observed that while ICOS expressing CD4+ and CD8+ T cells produced IFN-γ, ICOS−CD8+ T cells were also found to be producers of IFN-γ. However, we report that ICOS+CD8+ T cells were higher producers of IFN-γ than ICOS−CD8+ T cells. Moreover, correlation of ICOS expression with IFN-γ production in ICOS+IFN-γ+ T cell population (CD4+ and CD8+ T cells suggested that ICOS and IFN-γ could positively regulate each other. Further, master transcription factor T-bet importantly involved in regulating IFN-γ production was also found to be expressed by ICOS expressing CD4+ and CD8+ T cells during PbA infection. As noted above with IFN-γ and ICOS, a positive correlation of expression of ICOS with the transcription factor T-bet suggested that both of them could regulate each other. Taken together, our results depicted the importance of ICOS expressing CD4+ and CD8+ T cells in malaria parasite growth and lethality through IFN

Local Control and Survival Following Concomitant Chemoradiotherapy in Inoperable Stage I Non-Small-Cell Lung Cancer

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Campeau, Marie-Pierre; Herschtal, Alan; Wheeler, Greg; Mac Manus, Michael; Wirth, Andrew; Michael, Michael; Hogg, Annette; Drummond, Elizabeth; Ball, David

2009-01-01

Purpose: Concomitant chemoradiotherapy (CRT) increases survival rates compared with radical radiotherapy alone (RT) in Stage III non-small-cell lung cancer (NSCLC), as a result of improved local control. The effect of CRT on local control in Stage I NSCLC is less well documented. We retrospectively reviewed local control and survival following CRT or RT for inoperable Stage I NSCLC patients. Methods and materials: Eligible patients had histologically/cytologically proved inoperable Stage I NSCLC and had undergone complete staging investigations including an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Radiotherapy was planned as (1) 60 Gy in 30 fractions over 6 weeks with or without concomitant chemotherapy or (2) 50-55 Gy in 20 fractions without chemotherapy. Results: Between 2000 and 2005, 73 patients met the eligibility criteria and were treated as follows: CRT (60 Gy)-39; RT (60 Gy)-23; RT (50-55 Gy)-11. The median follow-up time for all patients was 18 months (range, 1-81 months). Survival analysis was based on intent to treat. Local progression-free survival (PFS) at 2 years was 66% with CRT and 55% with RT. The 2-year distant PFS was 60% following CRT and 63% after RT. The 2-year PFS rates were 57% and 50%, respectively. The 2-year survival rate for patients treated with CRT was 57% and 33% in patients receiving RT. Conclusions: Despite the use of CRT and routine staging with FDG-PET, both local and distant recurrences remain important causes of treatment failure in patients with inoperable stage I NSCLC.

A Novel Inflammation-Based Stage (I Stage Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma

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Jian-Pei Li

2016-11-01

Full Text Available Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS, modified GPS (mGPS and C-reactive protein/Albumin (CRP/Alb ratio, platelet–lymphocyte ratio (PLR, and neutrophil–lymphocyte ratio (NLR, have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC. In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR. The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03 and PLR (>146.2 were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves analyzed by receiver operating characteristics (ROC curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR = 2.093; 95% Confidence interval (CI: 1.222–3.587; p = 0.007 and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010 were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001. The I stage had a higher area under the curve value (0.670 compared with other systemic inflammation

Survival significance of epidermal growth factor receptor tyrosine kinase inhibitors and current staging system for survival after recurrence in patients with completely resected lung adenocarcinoma

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Saji H

2017-08-01

Full Text Available Hisashi Saji,1,2 Hiroki Sakai,1 Hiroyuki Kimura,1 Tomoyuki Miyazawa,1 Hideki Marushima,1 Haruhiko Nakamura1 1Department of Chest Surgery, St Marianna University School of Medicine, Miyamae-ku, Kawasaki, Kanagawa, Japan; 2Department of Thoracic Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan Objective: We previously reported that the staging system and epidermal growth factor receptor (EGFR mutation status are key factors for treatment strategy and predicting survival. However, the significance of these factors as predictors of overall survival (OS and postoperative recurrence survival (PRS has not been sufficiently elucidated. The objective here was to investigate EGFR mutation status and p-stage, which affect PRS and OS in patients with completely resected lung adenocarcinoma, using a different database.Patients and methods: We retrospectively reviewed 56 consecutive lung adenocarcinoma patients with disease recurrence in St. Marianna University Hospital between January 2010 and December 2014.Results: EGFR mutants (M were detected in 16/56 patients (29%. The patients with EGFR M had a better OS than those with EGFR wild-type (WT status (5-year survival: 50.3% vs 43.1, P=0.133. There was no significant difference in the 3-year recurrence-free survival rate between patients with M and WT (6.3% vs 7.7%, P=0.656, and the patients with EGFR M had a significantly better 3-year PRS than those with WT (77.4% vs 51.7%, P=0.033. The 3-year PRS rate for patients with M/pathologic stage (p-stage I–II (87.5% was better than that for patients with M/p-stage III (60.0%, WT/p-stage I–II (52.7%, and WT/p-stage III (43.8%. There was a significant difference between patients with M/p-stage I and WT/p-stage I–II or WT/p-stage III (P=0.021 and 0.030, respectively. During the study period, of the 16 patients with mutants, 12 patients (75% received EGFR-tyrosine kinase inhibitor (TKI therapy and among the 40 patients with WT, no patient received

Impact of Marital Status on Tumor Stage at Diagnosis and on Survival in Male Breast Cancer.

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Adekolujo, Orimisan Samuel; Tadisina, Shourya; Koduru, Ujwala; Gernand, Jill; Smith, Susan Jane; Kakarala, Radhika Ramani

2017-07-01

The effect of marital status (MS) on survival varies according to cancer type and gender. There has been no report on the impact of MS on survival in male breast cancer (MBC). This study aims to determine the influence of MS on tumor stage at diagnosis and survival in MBC. Men with MBC ≥18 years of age in the SEER database from 1990 to 2011 were included in the study. MS was classified as married and unmarried (including single, divorced, separated, widowed). Kaplan-Meier method was used to estimate the 5-year cancer-specific survival. Multivariate regression analyses were done to determine the effect of MS on presence of Stage IV disease at diagnosis and on cancer-specific mortality. The study included 3,761 men; 2,647 (70.4%) were married. Unmarried men were more often diagnosed with Stage IV MBC compared with married (10.7% vs. 5.5%, p Unmarried men (compared with married) were significantly less likely to undergo surgery (92.4% vs. 96.7%, p unmarried males with Stages II, III, and IV MBC have significantly worse 5-year cancer-specific survival compared with married. On multivariate analysis, being unmarried was associated with increased hazard of death (HR = 1.43, p Unmarried males with breast cancer are at greater risk for Stage IV disease at diagnosis and poorer outcomes compared with married males.

Is complete resection of high-risk stage IV neuroblastoma associated with better survival?

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Yeung, Fanny; Chung, Patrick Ho Yu; Tam, Paul Kwong Hang; Wong, Kenneth Kak Yuen

2015-12-01

The role of surgery in the management of stage IV neuroblastoma is controversial. In this study, we attempted to study if complete tumor resection had any impact on event-free survival (EFS) and overall survival (OS). A retrospective analysis of patients with stage IV neuroblastoma between November 2000 and July 2014 in a tertiary referral center was performed. Demographics data, extent of surgical resection, and outcomes were analyzed. A total of 34 patients with stage IV neuroblastoma according to International Neuroblastoma Staging System (INSS) were identified. The median age at diagnosis and operation was 3.5 (±1.9) years and 3.8 (±2.0) years, respectively. Complete gross tumor resection (CTR) was achieved in twenty-four patients (70.1%), in which one of the patients had nephrectomy and another had distal pancreatectomy. Gross total resection (GTR) with removal of >95% of tumor was performed in six patients (17.6%) and subtotal tumor resection (STR) with removal of >50%, but <95% of tumor was performed in four patients (11.8%). There was no statistical significance in terms of 5-year EFS and OS among the 3 groups. There was no surgery-related mortality or morbidity. From our center's experience, as there was no substantial survival benefit in stage IV neuroblastoma patients undergoing complete tumor resection, organ preservation and minimalization of morbidity should also be taken into consideration. Copyright © 2015. Published by Elsevier Inc.

Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells

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Müller Sylke

2009-05-01

Full Text Available Abstract Background Plasmodium falciparum-parasitized red blood cells (RBCs are equipped with protective antioxidant enzymes and heat shock proteins (HSPs. The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Methods Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. Results In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of

Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells.

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Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

2009-05-29

Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of

A life cycle database for parasitic acanthocephalans, cestodes, and nematodes

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Benesh, Daniel P.; Lafferty, Kevin D.; Kuris, Armand

2017-01-01

Parasitologists have worked out many complex life cycles over the last ~150 years, yet there have been few efforts to synthesize this information to facilitate comparisons among taxa. Most existing host-parasite databases focus on particular host taxa, do not distinguish final from intermediate hosts, and lack parasite life-history information. We summarized the known life cycles of trophically transmitted parasitic acanthocephalans, cestodes, and nematodes. For 973 parasite species, we gathered information from the literature on the hosts infected at each stage of the parasite life cycle (8510 host-parasite species associations), what parasite stage is in each host, and whether parasites need to infect certain hosts to complete the life cycle. We also collected life-history data for these parasites at each life cycle stage, including 2313 development time measurements and 7660 body size measurements. The result is the most comprehensive data summary available for these parasite taxa. In addition to identifying gaps in our knowledge of parasite life cycles, these data can be used to test hypotheses about life cycle evolution, host specificity, parasite life-history strategies, and the roles of parasites in food webs.

A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

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Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

2015-07-15

Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

Socioeconomic disparities in breast cancer survival: relation to stage at diagnosis, treatment and race

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Yu Xue

2009-10-01

Full Text Available Abstract Background Previous studies have documented lower breast cancer survival among women with lower socioeconomic status (SES in the United States. In this study, I examined the extent to which socioeconomic disparity in breast cancer survival was explained by stage at diagnosis, treatment, race and rural/urban residence using the Surveillance, Epidemiology, and End Results (SEER data. Methods Women diagnosed with breast cancer during 1998-2002 in the 13 SEER cancer registry areas were followed-up to the end of 2005. The association between an area-based measure of SES and cause-specific five-year survival was estimated using Cox regression models. Six models were used to assess the extent to which SES differences in survival were explained by clinical and demographical factors. The base model estimated the hazard ratio (HR by SES only and then additional adjustments were made sequentially for: 1 age and year of diagnosis; 2 stage at diagnosis; 3 first course treatment; 4 race; and 5 rural/urban residence. Results An inverse association was found between SES and risk of dying from breast cancer (p Conclusion Stage at diagnosis, first course treatment and race explained most of the socioeconomic disparity in breast cancer survival. Targeted interventions to increase breast cancer screening and treatment coverage in patients with lower SES could reduce much of socioeconomic disparity.

De novo assembly and characterization of the transcriptome of the parasitic weed dodder identifies genes associated with plant parasitism.

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Ranjan, Aashish; Ichihashi, Yasunori; Farhi, Moran; Zumstein, Kristina; Townsley, Brad; David-Schwartz, Rakefet; Sinha, Neelima R

2014-11-01

Parasitic flowering plants are one of the most destructive agricultural pests and have major impact on crop yields throughout the world. Being dependent on finding a host plant for growth, parasitic plants penetrate their host using specialized organs called haustoria. Haustoria establish vascular connections with the host, which enable the parasite to steal nutrients and water. The underlying molecular and developmental basis of parasitism by plants is largely unknown. In order to investigate the process of parasitism, RNAs from different stages (i.e. seed, seedling, vegetative strand, prehaustoria, haustoria, and flower) were used to de novo assemble and annotate the transcriptome of the obligate plant stem parasite dodder (Cuscuta pentagona). The assembled transcriptome was used to dissect transcriptional dynamics during dodder development and parasitism and identified key gene categories involved in the process of plant parasitism. Host plant infection is accompanied by increased expression of parasite genes underlying transport and transporter categories, response to stress and stimuli, as well as genes encoding enzymes involved in cell wall modifications. By contrast, expression of photosynthetic genes is decreased in the dodder infective stages compared with normal stem. In addition, genes relating to biosynthesis, transport, and response of phytohormones, such as auxin, gibberellins, and strigolactone, were differentially expressed in the dodder infective stages compared with stems and seedlings. This analysis sheds light on the transcriptional changes that accompany plant parasitism and will aid in identifying potential gene targets for use in controlling the infestation of crops by parasitic weeds. © 2014 American Society of Plant Biologists. All Rights Reserved.

Leishmania major glycosylation mutants require phosphoglycans (lpg2- but not lipophosphoglycan (lpg1- for survival in permissive sand fly vectors.

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Anna Svárovská

2010-01-01

Full Text Available Sand fly species able to support the survival of the protozoan parasite Leishmania have been classified as permissive or specific, based upon their ability to support a wide or limited range of strains and/or species. Studies of a limited number of fly/parasite species combinations have implicated parasite surface molecules in this process and here we provide further evidence in support of this proposal. We investigated the role of lipophosphoglycan (LPG and other phosphoglycans (PGs in sand fly survival, using Leishmania major mutants deficient in LPG (lpg1(-, and the phosphoglycan (PG-deficient mutant lpg2(-. The sand fly species used were the permissive species Phlebotomus perniciosus and P. argentipes, and the specific vector P. duboscqi, a species resistant to L. infantum development.The lpg2(- mutants did not survive well in any of the three sand fly species, suggesting that phosphoglycans and/or other LPG2-dependent molecules are required for parasite development. In vitro, all three L. major lines were equally resistant to proteolytic activity of bovine trypsin, suggesting that sand fly-specific hydrolytic proteases or other factors are the reason for the early lpg2(- parasite killing. The lpg1(- mutants developed late-stage infections in two permissive species, P. perniciosus and P. argentipes, where their infection rates and intensities of infections were comparable to the wild type (WT parasites. In contrast, in P. duboscqi the lpg1(- mutants developed significantly worse than the WT parasites.In combination with previous studies, the data establish clearly that LPG is not required for Leishmania survival in permissive species P. perniciosus and P. argentipes but plays an important role in the specific vector P. duboscqi. With regard to PGs other than LPG, the data prove the importance of LPG2-related molecules for survival of L. major in the three sand fly species tested.

A high parasite density environment induces transcriptional changes and cell death in Plasmodium falciparum blood stages.

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Chou, Evelyn S; Abidi, Sabia Z; Teye, Marian; Leliwa-Sytek, Aleksandra; Rask, Thomas S; Cobbold, Simon A; Tonkin-Hill, Gerry Q; Subramaniam, Krishanthi S; Sexton, Anna E; Creek, Darren J; Daily, Johanna P; Duffy, Michael F; Day, Karen P

2018-03-01

Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans. This species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria population size as a mechanism to possibly explain these in vivo observations. Specifically, Plasmodium falciparum blood stages from a high but not low-density environment exhibited unique phenotypic changes during the late trophozoite (LT) and schizont stages of the intraerythrocytic cycle. These included in order of appearance: failure of schizonts to mature and merozoites to replicate, apoptotic-like morphological changes including shrinking, loss of mitochondrial membrane potential, and blebbing with eventual release of aberrant parasites from infected erythrocytes. This unique death phenotype was triggered in a stage-specific manner by sensing of a high-density culture environment. Conditions of glucose starvation, nutrient depletion, and high lactate could not induce the phenotype. A high-density culture environment induced rapid global changes in the parasite transcriptome including differential expression of genes involved in cell remodeling, clonal antigenic variation, metabolism, and cell death pathways including an apoptosis-associated metacaspase gene. This transcriptional profile was also characterized by concomitant expression of asexual and sexual stage-specific genes. The data show strong evidence to support our hypothesis that density sensing exists in P. falciparum. They indicate that an apoptotic-like mechanism may play a role in P. falciparum density regulation, which, as in yeast, has features quite distinguishable from mammalian apoptosis. Gene expression data are available in the GEO databases under the accession number GSE91188. © 2017 Federation of European Biochemical Societies.

Trophic Relationships between the Parasitic Plant Species Phelipanche ramosa (L.) and Different Hosts Depending on Host Phenological Stage and Host Growth Rate

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Moreau, Delphine; Gibot-Leclerc, Stéphanie; Girardin, Annette; Pointurier, Olivia; Reibel, Carole; Strbik, Florence; Fernández-Aparicio, Mónica; Colbach, Nathalie

2016-01-01

Phelipanche ramosa (L.) Pomel (branched broomrape) is a holoparasitic plant that reproduces on crops and also on weeds, which contributes to increase the parasite seed bank in fields. This parasite extracts all its nutrients at the host’s expense so that host–parasite trophic relationships are crucial to determine host and parasite growth. This study quantified the intensity with which P. ramosa draws assimilates from its host and analyzed whether it varied with host species, host phenological stage and host growth rate. A greenhouse experiment was conducted on three host species: the crop species Brassica napus (L.) (oilseed rape) and two weed species, Capsella bursa-pastoris (L.) Medik. and Geranium dissectum (L.). Plants were grown with or without P. ramosa and under three light levels to modulate host growth rate. The proportion of host biomass loss due to parasitism by P. ramosa differed between host species (at host fructification, biomass loss ranged from 34 to 84%). B. napus and C. bursa-pastoris displayed a similar response to P. ramosa, probably because they belong to the same botanical family. The sensitivity to P. ramosa in each host species could be related to the precocity of P. ramosa development on them. Host compartments could be ranked as a function of their sensitivity to parasitism, with the reproductive compartment being the most severely affected, followed by stems and roots. The proportion of biomass allocated to leaves was not reduced by parasitism. The proportion of pathosystem biomass allocated to the parasite depended on host species. It generally increased with host stage progression but was constant across light induced-host growth rate, showing that P. ramosa adapts its growth to host biomass production. The rank order of host species in terms of sink strength differed from that in terms of host sensitivity. Finally, for B. napus, the biomass of individual parasite shoots decreased with increasing their number per host plant

Trophic relationships between the parasitic plant species Phelipanche ramosa (L. and different hosts depending on host phenological stage and host growth rate

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Delphine Moreau

2016-07-01

Full Text Available Phelipanche ramosa (L. Pomel (branched broomrape is a holoparasitic plant that reproduces on crops and also on weeds, which contributes to increase the parasite seed bank in fields. This parasite extracts all its nutrients at the host's expense so that host-parasite trophic relationships are crucial to determine host and parasite growth. This study quantified the intensity with which P. ramosa draws assimilates from its host and analyzed whether it varied with host species, host phenological stage and host growth rate. A greenhouse experiment was conducted on three host species: the crop species Brassica napus (L. (oilseed rape and two weed species, Capsella bursa-pastoris (L. Medik. and Geranium dissectum (L.. Plants were grown with or without P. ramosa and under three light levels to modulate host growth rate. The proportion of host biomass loss due to parasitism by P. ramosa differed between host species (at host fructification, biomass loss ranged from 34% to 84%. Brassica napus and C. bursa-pastoris displayed a similar response to P. ramosa, probably because they belong to the same botanical family. The sensitivity to P. ramosa in each host species could be related to the precocity of P. ramosa development on them. Host compartments could be ranked as a function of their sensitivity to parasitism, with the reproductive compartment being the most severely affected, followed by stems and roots. The proportion of biomass allocated to leaves was not reduced by parasitism. The proportion of pathosystem biomass allocated to the parasite depended on host species. It generally increased with host stage progression but was constant across light induced-host growth rate, showing that P. ramosa adapts its growth to host biomass production. The rank order of host species in terms of sink strength differed from that in terms of host sensitivity. Finally, for B. napus, the biomass of individual parasite shoots decreased with increasing their number per

Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

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Ian A Cockburn

2010-05-01

Full Text Available Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.

Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

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Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

2016-11-15

The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

Host-Parasite Interactions from the Inside: Plant Reproductive Ontogeny Drives Specialization in Parasitic Insects.

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Thomas Boivin

Full Text Available Host plant interactions are likely key drivers of evolutionary processes involved in the diversification of phytophagous insects. Granivory has received substantial attention for its crucial role in shaping the interaction between plants and their seed parasites, but fine-scale mechanisms explaining the role of host plant reproductive biology on specialization of seed parasites remain poorly described. In a comparative approach using plant histological techniques, we tested the hypotheses that different seed parasite species synchronize their life cycles to specific stages in seed development, and that the stage they target depends on major differences in seed development programs. In a pinaceous system, seed storage products are initiated before ovule fertilization and the wasps target the ovule's nucellus during megagametogenesis, a stage at which larvae may benefit from the by-products derived from both secreting cells and dying nucellar cells. In a cupressaceous system, oviposition activity peaks later, during embryogenesis, and the wasps target the ovule's megagametophyte where larvae may benefit from cell disintegration during embryogenesis. Our cytohistological approach shows for the first time how, despite divergent oviposition targets, different parasite species share a common strategy that consists of first competing for nutrients with developing plant structures, and then consuming these developed structures to complete their development. Our results support the prediction that seed developmental program is an axis for specialization in seed parasites, and that it could be an important parameter in models of their ecological and taxonomic divergence. This study provides the basis for further investigating the possibility of the link between plant ontogeny and pre-dispersal seed parasitism.

The influence of marital status on stage at diagnosis and survival of patients with colorectal cancer.

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Li, Qingguo; Gan, Lu; Liang, Lei; Li, Xinxiang; Cai, Sanjun

2015-03-30

Marital status was found to be an independent prognostic factor for survival in various cancer types, but it hasn't been fully studied in colorectal cancer (CRC). The Surveillance, Epidemiology and End Results database was used to compare survival outcomes with marital status in each stage. In total, 112, 776 eligible patients were identified. Patients in the widowed group were more frequently elderly women, more common of colon cancer, and more stage I/II in tumor stage (P married group (94.72% VS 94.10%). Married CRC patients had better 5year cause-specific survival (CSS) than those unmarried (P married patients at stage I (94.8% vs 89.8%, P vs 76.5%, P vs 53.9%, P VS 8.2%, P unmarried patients were at greater risk of cancer specific mortality. Despite favorable clinicpathological characteristics, widowed patients were at highest risk of death compared with other groups.

Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

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Shek, L L; Godolphin, W; Spinelli, J J

1987-12-01

The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation.

Survival of nonsurgically staged patients with negative lymphangiograms who had Stage IIB carcinoma of the cervix treated by pelvic radiation plus hydroxyurea

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Piver, M.S.; Krishnamsetty, R.M.; Emrich, L.J.

1985-01-01

Twenty patients with Stage IIB carcinoma of the cervix who did not undergo pretherapy para-aortic lymphadenectomy, but who had negative preradiation therapy lymphangiograms, were treated with pelvic radiation plus hydroxyurea. Patients received a median of 5020 rads of pelvic radiation plus 4000 rads of radium to point A. During radiation therapy and for a total of 12 weeks, patients received hydroxyurea administered at a dose of 80 mg/kg of body weight every 3 days if the white blood cell count was greater than or equal to 2,500/mm3 and platelets were greater than or equal to 75,000/mm3. The median follow-up time was 28 months (6 to 83 months). The estimated 5-year survival rate was 92%. Seventeen patients are alive with no evidence of disease (median, 28 months); one died of intercurrent disease with no evidence of disease (17 months); one is alive with no evidence of disease after recurrence (18 months); and one died of cervical cancer (22 months). The survival rate of patients with nonsurgically staged negative pretherapy lymphangiograms who had Stage IIB cervical cancer treated by pelvic radiation therapy plus hydroxyurea approximated the improved survival rate reported for patients with negative pretherapy para-aortic lymphadenectomy who were treated with pelvic radiation therapy plus hydroxyurea. Both studies would suggest that pelvic radiation plus hydroxyurea improves the rate of survival in patients with Stage IIB cervical cancer

Host-Parasite Interaction: Parasite-Derived and -Induced Proteases That Degrade Human Extracellular Matrix

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Carolina Piña-Vázquez

2012-01-01

Full Text Available Parasitic protozoa are among the most important pathogens worldwide. Diseases such as malaria, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and trypanosomiasis affect millions of people. Humans are constantly threatened by infections caused by these pathogens. Parasites engage a plethora of surface and secreted molecules to attach to and enter mammalian cells. The secretion of lytic enzymes by parasites into host organs mediates critical interactions because of the invasion and destruction of interstitial tissues, enabling parasite migration to other sites within the hosts. Extracellular matrix is a complex, cross-linked structure that holds cells together in an organized assembly and that forms the basement membrane lining (basal lamina. The extracellular matrix represents a major barrier to parasites. Therefore, the evolution of mechanisms for connective-tissue degradation may be of great importance for parasite survival. Recent advances have been achieved in our understanding of the biochemistry and molecular biology of proteases from parasitic protozoa. The focus of this paper is to discuss the role of protozoan parasitic proteases in the degradation of host ECM proteins and the participation of these molecules as virulence factors. We divide the paper into two sections, extracellular and intracellular protozoa.

Survival after Stage IA Endometrial Cancer; Can follow-up be altered?

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Lajer, Henrik; Elnegaard, Sandra; Christensen, René D

2012-01-01

IA (1988 classification) endometrial cancer patients prospectively included between 1986 and 1999. All patients had total abdominal hysterectomy and bilateral salpingo-oophorectomy without adjuvant therapy. Methods. The patient and the disease characteristics were drawn from the DEMCA database....... Of these recurrences, 15 of 23 (65%) were vaginal. Death from recurrence was observed in nine of 23 (39%) patients, and five of these nine had vaginal recurrences. Conclusions. Women with FIGO stage IA endometrial cancer have a very high disease-specific five year survival. Survival was related to histopathology...

Sensory Neuroanatomy of Parastrongyloides trichosuri, a Nematode Parasite of Mammals: Amphidial Neurons of the First-Stage Larva

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Zhu, He; Li, Jian; Nolan, Thomas J.; Schad, Gerhard A.; Lok, James B.

2011-01-01

Owing to its ability to switch between free-living and parasitic modes of development, Parastrongyloides trichosuri represents a valuable model with which to study the evolution of parasitism among the nematodes, especially aspects pertaining to morphogenesis of infective third-stage larvae. In the free-living nematode Caenorhabditis elegans, developmental fates of third-stage larvae are determined in part by environmental cues received by chemosensory neurons in the amphidial sensillae. As a basis for comparative study, we have described the neuroanatomy of the amphidial sensillae of P. trichosuri. Using computational methods we incorporated serial electron micrographs into a three-dimensional reconstruction of the amphidial neurons of this parasite. Each amphid is innervated by 13 neurons, and the dendritic processes of 10 of these extend nearly to the amphidial pore. Dendritic processes of two specialized neurons leave the amphidial channel and terminate within invaginations of the sheath cell. One of these is similar to the finger cell of C. elegans, terminating in digitiform projections. The other projects a single cilium into the sheath cell. The dendritic process of a third specialized neuron terminates within the tight junction of the amphid. Each amphidial neuron was traced from the tip of its dendrite(s) to its cell body in the lateral ganglion. Positions of these cell bodies approximate those of morphologically similar amphidial neurons in Caenorhabditis elegans, so the standard nomenclature for amphidial neurons in C. elegans was adopted. A map of cell bodies within the lateral ganglion of P. trichosuri was prepared to facilitate functional study of these neurons. PMID:21456026

Survival and Complication Rate of Radiation Therapy in Stage I and II Carcinoma of uterine Cervix

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Ma, Sun Young; Cho, Heung Lea; Sohn, Seung Chang

1995-01-01

Purpose : To analyze survival rate and late rectal and bladder complication for patients with stage with stage I and II carcinoma of uterine cervix treated by radiation alone or combined with chemotherapy. Materials and Methods : Between November 1984 and December 1993, 127 patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined therapy of radiation and chemotherapy. Retrospective analysis for survival rate was carried out on eligible 107 patients and review for complication was possible in 91 patients. The median follow-up was 47 months (range 3-118) and the median age of patients was 56 years (range 31-76). 26 patients were stage IB by FIGO classification. 40 were stage IIA and 41 were stage IIB. 86 cases were treated by radiation alone and 21 were treated by radiation and chemotherapy. 101 patients were treated with intracavitary radiation therapy (ICRT), of these, 80 were received low dose rate (LDR) ICRT and 21 were received high dose rate (HDR) ICRT. Of the patients who received LDR ICRT, 63 were treated by 1 intracavitary insertion and 17 were underwent 2 insertions. And we evaluated the external radiation dose and midline shield. Results : Acturial survival rate at 5 years was 92% for stage IB, 75% for stage IIA, 53% for stage IIB and 69% in all patients. Grade 1 rectal complications were developed in 20 cases(22%), grade 2 were in 22 cases (24%), 22 cases (24%) of grade 1 urinary complications and 17 cases (19%) of grade 2 urinary complications were observed But no patients had severe complications that needed surgical management or admission care. Maximum bladder dose for the group of patients with urinary complications was higher than that for the patients without urinary complications(7608cGy v 6960cGy, p<0.01). Maximum rectal dose for the group of patients with rectal complications was higher than that for the patients without urinary complications (7041cGy v 6269cGy, p<0.01). While there was no significant

Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism.

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Huan Peng

Full Text Available Pectate lyases are known to play a key role in pectin degradation by catalyzing the random cleavage of internal polymer linkages (endo-pectinases. In this paper, four novel cDNAs, designated Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7, that encode pectate lyases were cloned and characterized from the soybean cyst nematode, Heterodera glycines. The predicted protein sequences of HG-PEL-3, HG-PEL-4 and HG-PEL-6 differed significantly in both their amino acid sequences and their genomic structures from other pectate lyases of H. glycines (HG-PEL-1, HG-PEL-2 and HG-PEL-7. A phylogenetic study revealed that the pectate lyase proteins of H. glycines are clustered into distinct clades and have distinct numbers and positioning of introns, which suggests that the pectate lyase genes of H. glycines may have evolved from at least two ancestral genes. A Southern blot analysis revealed that multiple Hg-pel-6-like genes were present in the H. glycines genome. In situ hybridization showed that four novel pectate lyases (Hg-pel-3, Hg-pel-4, Hg-pel-6 and Hg-pel-7 were actively transcribed in the subventral esophageal gland cells. A semi-quantitative RT-PCR assay supported the finding that the expression of these genes was strong in the egg, pre-parasitic second-stage juvenile (J2 and early parasitic J2 stages and that it declined in further developmental stages of the nematode. This expression pattern suggests that these proteins play a role in the migratory phase of the nematode life cycle. Knocking down Hg-pel-6 using in vitro RNA interference resulted in a 46.9% reduction of the number of nematodes that invaded the plants and a 61.5% suppression of the development of H. glycines females within roots compared to the GFP-dsRNA control. Plant host-derived RNAi induced the silencing of the Hg-pel-6gene, which significantly reduced the nematode infection levels at 7 Days post inoculation (dpi. Similarly, this procedure reduced the number of female adults at 40 dpi

Insights on Heme Synthesis in the Malaria Parasite.

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Nagaraj, Viswanathan A; Padmanaban, Govindarajan

2017-08-01

The malaria parasite has a functional heme-biosynthetic pathway, although it can access host hemoglobin-heme. The heme pathway is dispensable for blood stages, but essential in the mosquito stages which do not acquire hemoglobin-heme. We propose that the blood stage parasites maintain a dynamic heme pool through multiple back-up mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma.

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Lan, Xiao-Wen; Zou, Xue-Bin; Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

2016-01-01

The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43-0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38-0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic

A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice.

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Andreas Greth

Full Text Available The blood stage of the plasmodium parasite life cycle is responsible for the clinical symptoms of malaria. Epidemiological studies have identified coincidental malarial endemicity and multiple red blood cell (RBC disorders. Many RBC disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections. However the mechanisms underpinning these genetic, host responses remain obscure. We have performed an N-ethyl-N-nitrosourea (ENU mutagenesis screen and have identified a novel dominant (haploinsufficient mutation in the Ank-1 gene (Ank1(MRI23420 of mice displaying hereditary spherocytosis (HS. Female mice, heterozygous for the Ank-1 mutation showed increased survival to infection by Plasmodium chabaudi adami DS with a concomitant 30% decrease in parasitemia compared to wild-type, isogenic mice (wt. A comparative in vivo red cell invasion and parasite growth assay showed a RBC-autonomous effect characterised by decreased proportion of infected heterozygous RBCs. Within approximately 6-8 hours post-invasion, TUNEL staining of intraerythrocytic parasites, showed a significant increase in dead parasites in heterozygotes. This was especially notable at the ring and trophozoite stages in the blood of infected heterozygous mutant mice compared to wt (p<0.05. We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites.

Clinical Predictors of Survival for Patients with Stage IV Cancer Referred to Radiation Oncology.

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Johnny Kao

Full Text Available There is an urgent need for a robust, clinically useful predictive model for survival in a heterogeneous group of patients with metastatic cancer referred to radiation oncology.From May 2012 to August 2013, 143 consecutive patients with stage IV cancer were prospectively evaluated by a single radiation oncologist. We retrospectively analyzed the effect of 29 patient, laboratory and tumor-related prognostic factors on overall survival using univariate analysis. Variables that were statistically significant on univariate analysis were entered into a multivariable Cox regression to identify independent predictors of overall survival.The median overall survival was 5.5 months. Four prognostic factors significantly predicted survival on multivariable analysis including ECOG performance status (0-1 vs. 2 vs. 3-4, number of active tumors (1 to 5 vs. ≥ 6, albumin levels (≥ 3.4 vs. 2.4 to 3.3 vs. 31.4 months for very low risk patients compared to 14.5 months for low risk, 4.1 months for intermediate risk and 1.2 months for high risk (p < 0.001.These data suggest that a model that considers performance status, extent of disease, primary tumor site and serum albumin represents a simple model to accurately predict survival for patients with stage IV cancer who are potential candidates for radiation therapy.

Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis.

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Rossi, Peter J; Jani, Ashesh B; Horowitz, Ira R; Johnstone, Peter A S

2008-01-01

To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p primary tumor was present, the addition of BT to EBRT was even more beneficial.

Quantifying Transmission Investment in Malaria Parasites.

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Megan A Greischar

2016-02-01

Full Text Available Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

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Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

2018-03-01

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer

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Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus

2016-01-01

AIM: To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. PATIENTS AND METHODS: A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. RESULTS......: There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA......+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. CONCLUSION: In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node...

Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

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Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

2017-11-01

In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

HIGH-THROUGHPUT IDENTIFICATION OF THE PREDOMINANT MALARIA PARASITE CLONE IN COMPLEX BLOOD STAGE INFECTIONS USING A MULTI-SNP MOLECULAR HAPLOTYPING ASSAY

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COLE-TOBIAN, JENNIFER L.; ZIMMERMAN, PETER A.; KING, CHRISTOPHER L.

2013-01-01

Individuals living in malaria endemic areas are often infected with multiple parasite clones. Currently used single nucleotide polymorphism (SNP) genotyping methods for malaria parasites are cumbersome; furthermore, few methods currently exist that can rapidly determine the most abundant clone in these complex infections. Here we describe an oligonucleotide ligation assay (OLA) to distinguish SNPs in the Plasmodium vivax Duffy binding protein gene (Pvdbp) at 14 polymorphic residues simultaneously. Allele abundance is determined by the highest mean fluorescent intensity of each allele. Using mixtures of plasmids encoding known haplotypes of the Pvdbp, single clones of P. vivax parasites from infected Aotus monkeys, and well-defined mixed infections from field samples, we were able to identify the predominant Pvdbp genotype with > 93% accuracy when the dominant clone is twice as abundant as a lesser genotype and > 97% of the time if the ratio was 5:1 or greater. Thus, the OLA can accurately, reproducibly, and rapidly determine the predominant parasite haplotype in complex blood stage infections. PMID:17255222

Subversion of complement by hematophagous parasites.

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Schroeder, Hélène; Skelly, Patrick J; Zipfel, Peter F; Losson, Bertrand; Vanderplasschen, Alain

2009-01-01

The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly microorganisms but also parasites, that have evolved countermeasures. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. In recent years, multiple complement evasion strategies have been characterized. In this review, we focus on complement escape mechanisms expressed by hematophagous parasites, a heterogeneous group of metazoan parasites that share the property of ingesting the whole blood of their host. Complement inhibition is crucial for parasite survival within the host tissue or to facilitate blood feeding. Finally, complement inhibition by hematophagous parasites may also contribute to their success as pathogen vectors.

Do stage of disease, comorbidity or access to treatment explain socioeconomic differences in survival after ovarian cancer?

DEFF Research Database (Denmark)

Ibfelt, Else Helene; Dalton, Susanne Oksbjerg; Høgdall, Claus

2015-01-01

educated women. After adjustment for comorbid conditions, cancer stage, tumour histology, operation status and lifestyle factors, socioeconomic differences in survival persisted. CONCLUSIONS: Socioeconomic disparities in survival after ovarian cancer were to some extent, but not fully explained...... we retrieved information on prognostic factors, treatment information and lifestyle factors. Age, vital status, comorbidity, education, income and cohabitation status were ascertained from nationwide administrative registers. Associations were analyzed with logistic regression and Cox regression...... models. RESULTS: Educational level was weakly associated with cancer stage. Short education, lower income and living without a partner were related to poorer survival after ovarian cancer. Among women with early cancer stage, HR (95% CI) for death was 1.75 (1.20-2.54) in shorter compared to longer...

Interface Molecules of Angiostrongylus cantonensis: Their Role in Parasite Survival and Modulation of Host Defenses

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Alessandra L. Morassutti

2012-01-01

Full Text Available Angiostrongylus cantonensis is a nematode parasite that causes eosinophilic meningoencephalitis in humans. Disease presents following the ingestion of third-stage larvae residing in the intermediate mollusk host and disease manifests as an acute inflammation of the meninges characterized by eosinophil infiltrates which release a battery of proinflammatory and cytotoxic agents in response to the pathogen. As a mechanism of neutralizing these host defenses, A. cantonensis expresses different molecules with immunomodulatory properties that are excreted or secreted (ES. In this paper we discuss the role of ES proteins on disease exacerbation and their potential use as therapeutic targets.

Trichinella inflammatory myopathy: host or parasite strategy?

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Chiumiento Lorena

2011-03-01

Full Text Available Abstract The parasitic nematode Trichinella has a special relation with muscle, because of its unique intracellular localization in the skeletal muscle cell, completely devoted in morphology and biochemistry to become the parasite protective niche, otherwise called the nurse cell. The long-lasting muscle infection of Trichinella exhibits a strong interplay with the host immune response, mainly characterized by a Th2 phenotype. The aim of this review is to illustrate the role of the Th2 host immune response at the muscle level during trichinellosis in different experimental models, such as knock-out or immuno-modulated mice. In particular, in knock-out mice a crucial role of IL-10 is evident for the regulation of inflammation intensity. The muscular host immune response to Trichinella is partially regulated by the intestinal phase of the parasite which emphasizes the intensity of the following muscle inflammation compared with animals infected by synchronized injections of newborn larvae. In eosinophil-ablated mice such as PHIL and GATA-- animals it was observed that there was an increased NOS2 expression in macrophages, driven by higher IFN-γ release, thus responsible for muscle larva damage. Besides modulation of the intestinal stage of the infection, using recombinant IL-12, increases the muscular parasite burden delaying adult worm expulsion from the intestine. Furthermore, a Th1 adjuvant of bacterial origin called Helicobacter pylori neutrophil activating protein (HP-NAP, administered during the intestinal phase of trichinellosis, alters the Th2 dependent response at muscle level. All these data from the literature delineate then a mutual adaptation between parasite and host immune response in order to achieve a strategic compromise between two evolutionary forces pointed towards the survival of both species.

Global gene expression analysis of the zoonotic parasite Trichinella spiralis revealed novel genes in host parasite interaction.

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Xiaolei Liu

Full Text Available BACKGROUND: Trichinellosis is a typical food-borne zoonotic disease which is epidemic worldwide and the nematode Trichinella spiralis is the main pathogen. The life cycle of T. spiralis contains three developmental stages, i.e. adult worms, new borne larva (new borne L1 larva and muscular larva (infective L1 larva. Stage-specific gene expression in the parasites has been investigated with various immunological and cDNA cloning approaches, whereas the genome-wide transcriptome and expression features of the parasite have been largely unknown. The availability of the genome sequence information of T. spiralis has made it possible to deeply dissect parasite biology in association with global gene expression and pathogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we analyzed the global gene expression patterns in the three developmental stages of T. spiralis using digital gene expression (DGE analysis. Almost 15 million sequence tags were generated with the Illumina RNA-seq technology, producing expression data for more than 9,000 genes, covering 65% of the genome. The transcriptome analysis revealed thousands of differentially expressed genes within the genome, and importantly, a panel of genes encoding functional proteins associated with parasite invasion and immuno-modulation were identified. More than 45% of the genes were found to be transcribed from both strands, indicating the importance of RNA-mediated gene regulation in the development of the parasite. Further, based on gene ontological analysis, over 3000 genes were functionally categorized and biological pathways in the three life cycle stage were elucidated. CONCLUSIONS AND SIGNIFICANCE: The global transcriptome of T. spiralis in three developmental stages has been profiled, and most gene activity in the genome was found to be developmentally regulated. Many metabolic and biological pathways have been revealed. The findings of the differential expression of several protein

Lundep, a sand fly salivary endonuclease increases Leishmania parasite survival in neutrophils and inhibits XIIa contact activation in human plasma.

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Andrezza C Chagas

2014-02-01

Full Text Available Neutrophils are the host's first line of defense against infections, and their extracellular traps (NET were recently shown to kill Leishmania parasites. Here we report a NET-destroying molecule (Lundep from the salivary glands of Lutzomyia longipalpis. Previous analysis of the sialotranscriptome of Lu. longipalpis showed the potential presence of an endonuclease. Indeed, not only was the cloned cDNA (Lundep shown to encode a highly active ss- and dsDNAse, but also the same activity was demonstrated to be secreted by salivary glands of female Lu. longipalpis. Lundep hydrolyzes both ss- and dsDNA with little sequence specificity with a calculated DNase activity of 300000 Kunitz units per mg of protein. Disruption of PMA (phorbol 12 myristate 13 acetate- or parasite-induced NETs by treatment with recombinant Lundep or salivary gland homogenates increases parasite survival in neutrophils. Furthermore, co-injection of recombinant Lundep with metacyclic promastigotes significantly exacerbates Leishmania infection in mice when compared with PBS alone or inactive (mutagenized Lundep. We hypothesize that Lundep helps the parasite to establish an infection by allowing it to escape from the leishmanicidal activity of NETs early after inoculation. Lundep may also assist blood meal intake by lowering the local viscosity caused by the release of host DNA and as an anticoagulant by inhibiting the intrinsic pathway of coagulation.

Paradigms for parasite conservation.

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Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

2016-08-01

Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

Survival of weed seeds and animal parasites as affected by anaerobic digestion at meso- and thermophilic conditions

DEFF Research Database (Denmark)

Johansen, Anders; Bangsø Nielsen, Henrik; Hansen, Christian M.

2013-01-01

did not affect egg survival during the first 48h and it took up to 10days before total elimination was reached. In general, anaerobic digestion in biogas plants seems an efficient way (thermophilic more efficient than mesophilic) to treat organic farm wastes in a way that suppresses animal parasites......, Ascaris suum, was assessed under conditions similar to biogas plants managed at meso- (37°C) and thermophilic (55°C) conditions. Cattle manure was used as digestion substrate and experimental units were sampled destructively over time. Regarding weed seeds, the effect of thermophilic conditions (55°C...

Growth and survival of sea lampreys from metamorphosis to spawning in Lake Huron

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Swink, William D.; Johnson, Nicholas S.

2014-01-01

Larval Sea Lampreys Petromyzon marinus live burrowed in stream bottoms and then metamorphose into their parasitic stage. Among larvae that metamorphose in a given year (i.e., parasitic cohort), autumn out-migrants (October–December) to the Laurentian Great Lakes can feed on fish for up to 6 months longer than spring outmigrants (March–May), which overwinter in streams without feeding. We evaluated whether the season of outmigration affected growth or survival of newlymetamorphosed Sea Lampreys in LakeHuron. Newlymetamorphosed individuals (n=2,718) from three parasitic cohorts were netted during their out-migration from BlackMallard Creek, Michigan, to LakeHuron during autumn 1997 through spring 2000; each out-migrant was injected with a sequentially numbered coded wire tag and was released back into the creek. After up to 18 months of feeding in the Great Lakes, 224 (8.2%) Sea Lampreys were recaptured (in 1999–2001) as upstream-migrating adults in tributaries to Lakes Huron and Michigan. Recovery rates of autumn and spring out-migrants as adults were 9.4% and 7.8%, respectively, and these rates did not significantly differ. Overwinter feeding (i.e., as parasites) by autumn out-migrants did not produce adult mean sizes greater than those of spring out-migrants. Because we detected no growth or survival differences between autumn and spring out-migrants, the capture of newly metamorphosed Sea Lampreys at any point during their out-migration should provide equal reductions in damage to Great Lakes fisheries. The absence of a difference in growth or survival between autumn and spring out-migrants is an aspect of Sea Lamprey life history that yields resiliency to this invasive parasite and complicates efforts for its control in the Great Lakes.

De Novo Assembly and Characterization of the Transcriptome of the Parasitic Weed Dodder Identifies Genes Associated with Plant Parasitism1[C][W][OPEN

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Ranjan, Aashish; Ichihashi, Yasunori; Farhi, Moran; Zumstein, Kristina; Townsley, Brad; David-Schwartz, Rakefet; Sinha, Neelima R.

2014-01-01

Parasitic flowering plants are one of the most destructive agricultural pests and have major impact on crop yields throughout the world. Being dependent on finding a host plant for growth, parasitic plants penetrate their host using specialized organs called haustoria. Haustoria establish vascular connections with the host, which enable the parasite to steal nutrients and water. The underlying molecular and developmental basis of parasitism by plants is largely unknown. In order to investigate the process of parasitism, RNAs from different stages (i.e. seed, seedling, vegetative strand, prehaustoria, haustoria, and flower) were used to de novo assemble and annotate the transcriptome of the obligate plant stem parasite dodder (Cuscuta pentagona). The assembled transcriptome was used to dissect transcriptional dynamics during dodder development and parasitism and identified key gene categories involved in the process of plant parasitism. Host plant infection is accompanied by increased expression of parasite genes underlying transport and transporter categories, response to stress and stimuli, as well as genes encoding enzymes involved in cell wall modifications. By contrast, expression of photosynthetic genes is decreased in the dodder infective stages compared with normal stem. In addition, genes relating to biosynthesis, transport, and response of phytohormones, such as auxin, gibberellins, and strigolactone, were differentially expressed in the dodder infective stages compared with stems and seedlings. This analysis sheds light on the transcriptional changes that accompany plant parasitism and will aid in identifying potential gene targets for use in controlling the infestation of crops by parasitic weeds. PMID:24399359

The Redox Cycler Plasmodione Is a Fast-Acting Antimalarial Lead Compound with Pronounced Activity against Sexual and Early Asexual Blood-Stage Parasites.

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Ehrhardt, Katharina; Deregnaucourt, Christiane; Goetz, Alice-Anne; Tzanova, Tzvetomira; Gallo, Valentina; Arese, Paolo; Pradines, Bruno; Adjalley, Sophie H; Bagrel, Denyse; Blandin, Stephanie; Lanzer, Michael; Davioud-Charvet, Elisabeth

2016-09-01

Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox cyclers-a strategy that is broadly recognized for the development of new antimalarial agents. Here we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intraerythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intraerythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common mechanisms of resistance to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a high killing speed, as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that plasmodione is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Cervical cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study.

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Benard, Vicki B; Watson, Meg; Saraiya, Mona; Harewood, Rhea; Townsend, Julie S; Stroup, Antoinette M; Weir, Hannah K; Allemani, Claudia

2017-12-15

Overall, cervical cancer survival in the United States has been reported to be among the highest in the world, despite slight decreases over the last decade. Objective of the current study was to describe cervical cancer survival trends among US women and examine differences by race and stage. This study used data from the CONCORD-2 study to compare survival among women (aged 15-99 years) diagnosed in 37 states covering 80% of the US population. Survival was adjusted for background mortality (net survival) with state- and race-specific life tables and was age-standardized with the International Cancer Survival Standard weights. Five-year survival was compared by race (all races, blacks, and whites). Two time periods, 2001-2003 and 2004-2009, were considered because of changes in how the staging variable was collected. From 2001 to 2009, 90,620 women were diagnosed with invasive cervical cancer. The proportion of cancers diagnosed at a regional or distant stage increased over time in most states. Overall, the 5-year survival was 63.5% in 2001-2003 and 62.8% in 2004-2009. The survival was lower for black women versus white women in both calendar periods and in most states; black women had a higher proportion of distant-stage cancers. The stability of the overall survival over time and the persistent differences in survival between white and black women in all US states suggest that there is a need for targeted interventions and improved access to screening, timely treatment, and follow-up care, especially among black women. Cancer 2017;123:5119-37. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Unusual thiol-based redox metabolism of parasitic flukes.

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Tripathi, Timir; Suttiprapa, Sutas; Sripa, Banchob

2017-08-01

Parasitic flukes are exposed to free radicals and, to a greater extent, reactive oxygen species (ROS) during their life cycle. Despite being relentlessly exposed to ROS released by activated immune cells, these parasites can survive for many years in the host. Cellular thiol-based redox metabolism plays a crucial role in parasite survival within their hosts. Evidence shows that oxidative stress and redox homeostasis maintenance are important clinical and pathobiochemical as well as effective therapeutic principles in various diseases. The characterization of redox and antioxidant enzymes is likely to yield good target candidates for novel drugs and vaccines. The absence of active catalase in fluke parasites offers great potential for the development of chemotherapeutic agents that act by perturbing the redox equilibrium of the cell. One of the redox-sensitive enzymes, thioredoxin glutathione reductase (TGR), has been accepted as a drug target against blood fluke infections, and related clinical trials are in progress. TGR is the sole enzyme responsible for Trx and GSH reduction in parasitic flukes. The availability of helminth genomes has accelerated the research on redox metabolism of flukes; however, significant achievements have yet to be attained. The present review summarizes current knowledge on the redox and antioxidant system of the parasitic flukes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of Irradiation on Insect Host-Parasite Relationship

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Rahalkar, G. W.; Ramakrishnan, V. [Biology Division, Bhabha Atomic Research Centre, Trombay, Bombay (India)

1968-06-15

Effects of host irradiation on the development of its parasite were investigated. Females of Bracon brevicomis readily accepted irradiated larvae of tile wax moth (Galleria mellonella) and rice moth (Corcyra cephalonica) for oviposition. However, irradiated wax moth larvae adversely influenced the viability of eggs laid on them and also the survival of the parasite grubs feeding on their bodies. The female grubs were affected more than the males. Rice moth larvae, on the other hand, exerted no significant influence on the viability of parasite eggs, but adversely affected the survival of the grubs. The progeny of parents that had been reared on irradiated larvae also exhibited some developmental changes although grown on non-irradiated host larvae, and these changes were more pronounced when G. mellonella was used as the host insect. (author)

Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 in the surface expression of malaria parasite var proteins

DEFF Research Database (Denmark)

Goel, Suchi; Valiyaveettil, Manojkumar; Achur, Rajeshwara N

2010-01-01

adherence. However, how CLAG9 influences this process remains unknown. In this study, we show that CLAG9 interacts with VAR2CSA, a PfEMP1 that mediates IRBC adherence to chondroitin 4-sulfate in the placenta. Importantly, our results show that the adherent parasites synthesize CLAG9 at two stages--the early......Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate the adherence of parasite-infected red blood cells (IRBCs) to various host receptors. A previous study has shown that the parasite protein, cytoadherence-linked asexual gene 9 (CLAG9), is also essential for IRBC...... within the parasite. Based on these findings, we propose that CLAG9 plays a critical role in the trafficking of PfEMP1s onto the IRBC surface. These results have important implications for the development of therapeutics for cerebral, placental, and other cytoadherence-associated malaria illnesses....

Radiation therapy and patient age in the survival from early-stage breast cancer

International Nuclear Information System (INIS)

Joslyn, Sue A.

1999-01-01

Purpose: To analyze the use of radiation therapy following local excision of invasive localized breast cancer and subsequent survival by 5-year age category. Methods: Data for 27,399 women diagnosed with localized stage of breast cancer and treated with local excision surgery from 1983 through 1992 were collected and provided by the national Surveillance, Epidemiology, and End Results (SEER) program. Use of radiation therapy was analyzed by race, ethnic background, geographic location, and age at diagnosis. Survival for women treated with local excision plus radiation therapy was compared to that of women treated with local excision alone for each 5-year age category. Results: Subjects in older age groups were significantly less likely (p < 0.001) to receive radiation following local excision compared to younger age groups. Statistically significant survival advantages were conferred on women receiving radiation therapy in each 5-year age category from age 35 to 84 years (ranging from p = 0.02 to p < 0.0001). Conclusion: While the use of radiation therapy following local excision of early-stage breast tumors drops significantly in older age groups, women aged 35-84 years receiving radiation therapy had significant reductions in mortality. These results did not appear to be influenced by the presence of mortal comorbid conditions. These results strongly suggest the need to consider carefully patient characteristics other than age in deciding the course of treatment for early-stage breast cancer

Impacts of parasite infection on columnaris disease of tilapia

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There is no information available on whether parasite infection will increase the susceptibility of tilapia to Flavobacterium columnare and whether parasite treatment could improve fish survival after F. columnare exposure. Two trials were conducted to evaluate 1) the susceptibility of hybrid tilapi...

Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and gender-specific proteomic profiling.

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Sasisekhar Bennuru

Full Text Available Relatively little is known about the filarial proteins that interact with the human host. Although the filarial genome has recently been completed, protein profiles have been limited to only a few recombinants or purified proteins of interest. Here, we describe a large-scale proteomic analysis using microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry to identify the excretory-secretory (ES products of the L3, L3 to L4 molting ES, adult male, adult female, and microfilarial stages of the filarial parasite Brugia malayi. The analysis of the ES products from adult male, adult female, microfilariae (Mf, L3, and molting L3 larvae identified 852 proteins. Annotation suggests that the functional and component distribution was very similar across each of the stages studied; however, the Mf contributed a higher proportion to the total number of identified proteins than the other stages. Of the 852 proteins identified in the ES, only 229 had previous confirmatory expressed sequence tags (ESTs in the available databases. Moreover, this analysis was able to confirm the presence of 274 "hypothetical" proteins inferred from gene prediction algorithms applied to the B. malayi (Bm genome. Not surprisingly, the majority (160/274 of these "hypothetical" proteins were predicted to be secreted by Signal IP and/or SecretomeP 2.0 analysis. Of major interest is the abundance of previously characterized immunomodulatory proteins such as ES-62 (leucyl aminopeptidase, MIF-1, SERPIN, glutathione peroxidase, and galectin in the ES of microfilariae (and Mf-containing adult females compared to the adult males. In addition, searching the ES protein spectra against the Wolbachia database resulted in the identification of 90 Wolbachia-specific proteins, most of which were metabolic enzymes that have not been shown to be immunogenic. This proteomic analysis extends our knowledge of the ES and provides insight into the host-parasite interaction.

Does stage of cancer, comorbidity or lifestyle factors explain educational differences in survival after endometrial cancer?

DEFF Research Database (Denmark)

Seidelin, Ulla Holten; Ibfelt, Else; Andersen, Ingelise

2016-01-01

characteristics, surgery, body mass index (BMI) and smoking status. Information on highest attained education, cohabitation and comorbidity was obtained from nationwide administrative registries. Logistic regression models were used to determine the association between level of education and cancer stage and Cox......Background: Several studies have documented an association between socioeconomic position and survival from gynaecological cancer, but the mechanisms are unclear. Objective: The aim of this study was to examine the association between level of education and survival after endometrial cancer among...... Danish women; and whether differences in stage at diagnosis and comorbidity contribute to the educational differences in survival. Methods: Women with endometrial cancer diagnosed between 2005 and 2009 were identified in the Danish Gynaecological Cancer Database, with information on clinical...

A common-garden experiment to quantify evolutionary processes in copepods: the case of emamectin benzoate resistance in the parasitic sea louse Lepeophtheirus salmonis.

Science.gov (United States)

Ljungfeldt, Lina Eva Robin; Espedal, Per Gunnar; Nilsen, Frank; Skern-Mauritzen, Mette; Glover, Kevin Alan

2014-05-19

The development of pesticide resistance represents a global challenge to food production. Specifically for the Atlantic salmon aquaculture industry, parasitic sea lice and their developing resistance to delousing chemicals is challenging production. In this study, seventeen full sibling families, established from three strains of Lepeophtheirus salmonis displaying differing backgrounds in emamectin benzoate (EB) tolerance were produced and quantitatively compared under a common-garden experimental design. Lice surviving to the preadult stage were then exposed to EB and finally identified through the application of DNA parentage testing. With the exception of two families (19 and 29%), survival from the infectious copepod to preadult stage was very similar among families (40-50%). In contrast, very large differences in survival following EB exposure were observed among the families (7.9-74%). Family survival post EB exposure was consistent with the EB tolerance characteristics of the strains from which they were established and no negative effect on infection success were detected in association with increased EB tolerance. Two of the lice families that displayed reduced sensitivity to EB were established from a commercial farm that had previously used this chemical. This demonstrates that resistant alleles were present on this farm even though the farm had not reported treatment failure. To our knowledge, this represents the first study where families of any multi-cellular parasite have been established and compared in performance under communal rearing conditions in a common-garden experiment. The system performed in a predictable manner and permitted, for the first time, elucidation of quantitative traits among sea lice families. While this experiment concentrated on, and provided a unique insight into EB sensitivity among lice families, the experimental design represents a novel methodology to experimentally address both resistance development and other

The impact of lymph vascular space invasion on recurrence and survival in patients with early stage endometrial cancer.

Science.gov (United States)

Loizzi, V; Cormio, G; Lorusso, M; Latorre, D; Falagario, M; Demitri, P; Scardigno, D; Selvaggi, L E

2014-05-01

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement. © 2013 John Wiley & Sons Ltd.

Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival

International Nuclear Information System (INIS)

Gomez, Daniel R.; Liao, Kai-Ping; Swisher, Stephen G.; Blumenschein, George R.; Erasmus, Jeremy J.; Buchholz, Thomas A.; Giordano, Sharon H.; Smith, Benjamin D.

2015-01-01

Purpose: Prompt staging and treatment are crucial for non-small cell lung cancer (NSCLC). We determined if predictors of treatment delay after diagnosis were associated with prognosis. Materials and methods: Medicare claims from 28,732 patients diagnosed with NSCLC in 2004–2007 were used to establish the diagnosis-to-treatment interval (ideally ⩽35 days) and identify staging studies during that interval. Factors associated with delay were identified with multivariate logistic regression, and associations between delay and survival by stage were tested with Cox proportional hazard regression. Results: Median diagnosis-to-treatment interval was 27 days. Receipt of PET was associated with delays (57.4% of patients with PET delayed [n = 6646/11,583] versus 22.8% of those without [n = 3908/17,149]; adjusted OR = 4.48, 95% CI 4.23–4.74, p < 0.001). Median diagnosis-to-PET interval was 15 days; PET-to-clinic, 5 days; and clinic-to-treatment, 12 days. Diagnosis-to-treatment intervals <35 days were associated with improved survival for patients with localized disease and those with distant disease surviving ⩾1 year but not for patients with distant disease surviving <1 year. Conclusion: Delays between diagnosing and treating NSCLC are common and associated with use of PET for staging. Reducing time to treatment may improve survival for patients with manageable disease at diagnosis

Maternal androgens in avian brood parasites and their hosts: responses to parasitism and competition?

Science.gov (United States)

Hahn, Caldwell; Wingfield, John C.; Fox, David M.; Walker, Brian G.; Thomley, Jill E

2017-01-01

In the coevolutionary dynamic of avian brood parasites and their hosts, maternal (or transgenerational) effects have rarely been investigated. We examined the potential role of elevated yolk testosterone in eggs of the principal brood parasite in North America, the brown-headed cowbird, and three of its frequent host species. Elevated maternal androgens in eggs are a common maternal effect observed in many avian species when breeding conditions are unfavorable. These steroids accelerate embryo development, shorten incubation period, increase nestling growth rate, and enhance begging vigor, all traits that can increase the survival of offspring. We hypothesized that elevated maternal androgens in host eggs are a defense against brood parasitism. Our second hypothesis was that elevated maternal androgens in cowbird eggs are a defense against intra-specific competition. For host species, we found that elevated yolk testosterone was correlated with parasitized nests of small species, those whose nest success is most reduced by cowbird parasitism. For cowbirds, we found that elevated yolk testosterone was correlated with eggs in multiply-parasitized nests, which indicate intra-specific competition for nests due to high cowbird density. We propose experimental work to further examine the use of maternal effects by cowbirds and their hosts.

Application of small RNA technology for improved control of parasitic helminths.

Science.gov (United States)

Britton, Collette; Winter, Alan D; Marks, Neil D; Gu, Henry; McNeilly, Tom N; Gillan, Victoria; Devaney, Eileen

2015-08-15

Over the last decade microRNAs (miRNAs) and small interfering RNAs (siRNAs) have emerged as important regulators of post-transcriptional gene expression. miRNAs are short, non-coding RNAs that regulate a variety of processes including cancer, organ development and immune function. This class of small RNAs bind with partial complementarity to their target mRNA sequences, most often in the 3'UTR, to negatively regulate gene expression. In parasitic helminths, miRNAs are being increasingly studied for their potential roles in development and host-parasite interactions. The availability of genome data, combined with small RNA sequencing, has paved the way to profile miRNAs expressed at particular developmental stages for many parasitic helminths. While some miRNAs are conserved across species, others appear to be unique to specific parasites, suggesting important roles in adaptation and survival in the host environment. Some miRNAs are released from parasites, in exosomes or in protein complexes, and the potential effects of these on host immune function are being increasingly studied. In addition, release of miRNAs from schistosome and filarial parasites into host plasma can be exploited for the development of specific and sensitive diagnostic biomarkers of infection. Interfering with miRNA function, as well as silencing key components of the pathways they regulate, will progress our understanding of parasite development and provide a novel approach to therapeutic control. RNA interference (RNAi) by siRNAs has proven to be inconsistent in parasitic nematodes. However, the recent successes reported for schistosome and liver fluke RNAi, encourage further efforts to enhance delivery of RNA and improve in vitro culture systems and assays to monitor phenotypic effects in nematodes. These improvements are important for the establishment of reliable functional genomic platforms for novel drug and vaccine development. In this review we focus on the important roles of mi

Spatio-temporal variability in western Baltic cod early life stage survival mediated by egg buoyancy, hydrography and hydrodynamics

DEFF Research Database (Denmark)

Hinrichsen, H-H.; Hüssy, K.; Huwer, B.

2012-01-01

Spatio-temporal variability in western Baltic cod early life stage survival mediated by egg buoyancy, hydrography and hydrodynamics. – ICES Journal of Marine Science, 69: 1744–1752.To disentangle the effects of different drivers on recruitment variability of marine fish, a spatially and temporally...... explicit understanding of both the spawning stock size and the early life stage dynamics is required. The objectives of this study are to assess the transport of western Baltic cod early life stages as well as the variability in environmentally-mediated survival along drift routes in relation to both...

Signaling in Parasitic Nematodes: Physicochemical Communication Between Host and Parasite and Endogenous Molecular Transduction Pathways Governing Worm Development and Survival.

Science.gov (United States)

Lok, James B

2016-12-01

Signaling or communication between host and parasite may occur over relatively long ranges to enable host finding and acquisition by infective parasitic nematode larvae. Innate behaviors in infective larvae transmitted from the soil that enhance the likelihood of host contact, such as negative geotaxis and hypermotility, are likely mediated by mechanoreception and neuromuscular signaling. Host cues such as vibration of the substratum, elevated temperature, exhaled CO 2 , and other volatile odorants are perceived by mechanosensory and chemosensory neurons of the amphidial complex. Beyond this, the molecular systems that transduce these external cues within the worm are unknown at this time. Overall, the signal transduction mechanisms that regulate switching between dauer and continuous reproductive development in Caenorhabditis elegans , and doubtless other free-living nematodes, have provided a useful framework for testing hypotheses about how the morphogenesis and development of infective parasitic nematode larvae and the lifespan of adult parasites are regulated. In C. elegans , four major signal transduction pathways, G protein-coupled receptor signaling, insulin/insulin-like growth factor signaling, TGFβ-like signaling and steroid-nuclear hormone receptor signaling govern the switch between dauer and continuous development and regulate adult lifespan. Parasitic nematodes appear to have conserved the functions of G-protein-coupled signaling, insulin-like signaling and steroid-nuclear hormone receptor signaling to regulate larval development before and during the infective process. By contrast, TGFβ-like signaling appears to have been adapted for some other function, perhaps modulation of the host immune response. Of the three signal transduction pathways that appear to regulate development in parasitic nematodes, steroid-nuclear hormone signaling is the most straightforward to manipulate with administered small molecules and may form the basis of new

Blood transfusion and survival after surgery for Stage I and II breast cancer

International Nuclear Information System (INIS)

Herman, K.; Kolodziejski, L.

1993-01-01

The records of 690 Stage I and II breast cancer patients (31% of them with transfusions), who underwent mastectomy with axillary dissection were examined whether perioperative blood transfusion might be detrimental to survival. The overall 5- and 1-year survival rates for 477 patients who had not received transfusions were 75% and 63% respectively, compared with 66% and 49% for those who had transfusions (p=0.005). There was no significant difference between the group in any other of the most important prognostic factors. An analysis of the subpopulation of patients with favorable prognostic factors yielded similar results. A multivariate analysis indicated that blood transfusion was one of the four variables significantly related to survival. (author)

Early life stages of Northern shrimp (Pandalus borealis) are sensitive to fish feed containing the anti-parasitic drug diflubenzuron.

Science.gov (United States)

Bechmann, Renée Katrin; Lyng, Emily; Westerlund, Stig; Bamber, Shaw; Berry, Mark; Arnberg, Maj; Kringstad, Alfhild; Calosi, Piero; Seear, Paul J

2018-05-01

Increasing use of fish feed containing the chitin synthesis inhibiting anti-parasitic drug diflubenzuron (DFB) in salmon aquaculture has raised concerns over its impact on coastal ecosystems. Larvae of Northern shrimp (Pandalus borealis) were exposed to DFB medicated feed under Control conditions (7.0 °C, pH 8.0) and under Ocean Acidification and Warming conditions (OAW, 9.5 °C and pH 7.6). Two weeks' exposure to DFB medicated feed caused significantly increased mortality. The effect of OAW and DFB on mortality of shrimp larvae was additive; 10% mortality in Control, 35% in OAW, 66% in DFB and 92% in OAW + DFB. In OAW + DFB feeding and swimming activity were reduced for stage II larvae and none of the surviving larvae developed to stage IV. Two genes involved in feeding (GAPDH and PRLP) and one gene involved in moulting (DD9B) were significantly downregulated in larvae exposed to OAW + DFB relative to the Control. Due to a shorter intermoult period under OAW conditions, the OAW + DFB larvae were exposed throughout two instead of one critical pre-moult period. This may explain the more serious sub-lethal effects for OAW + DFB than DFB larvae. A single day exposure at 4 days after hatching did not affect DFB larvae, but high mortality was observed for OAW + DFB larvae, possibly because they were exposed closer to moulting. High mortality of shrimp larvae exposed to DFB medicated feed, indicates that the use of DFB in salmon aquaculture is a threat to crustacean zooplankton. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Antiparasitic efficacy of ivermectin in naturally parasitized sheep.

Science.gov (United States)

Yazwinski, T A; Greenway, T; Presson, B L; Pote, L M; Featherstone, H; Williams, M

1983-11-01

Sixteen sheep harboring naturally acquired parasitisms were allocated to 1 of 2 treatment groups: (i) sheep given ivermectin in an oral solution at the dosage rate of 200 micrograms/kg of body weight, and (ii) those given the vehicle at a dosage rate of 0.25 ml/kg. All animals were necropsied at 2 weeks after treatment. Parasites and percentages of parasitic reductions, as demonstrated in this trial, were: Dictyocaulus filaria (99.4%), Oestrus ovis first stage instars (100%), Trichuris ovis (98.9%), Strongyloides papillosus (99.8%), Nematodirus spathiger (100%), arrested 4th stage Nematodirus spp (96.2%), Trichostrongylus colubriformis (100%), T axei (100%), Oster tagia circumcincta (100%), Haemonchus contortus (100%), and arrested Haemonchus spp 4th stage larvae (99.9%). The sheep showed no adverse effects due to ivermectin or vehicle administration.

Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

Science.gov (United States)

Babayan, Simon A; Read, Andrew F; Lawrence, Rachel A; Bain, Odile; Allen, Judith E

2010-10-19

Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependent development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

Directory of Open Access Journals (Sweden)

Simon A Babayan

Full Text Available Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependent development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

Survival after early-stage breast cancer of women previously treated for depression

DEFF Research Database (Denmark)

Suppli, Nis Frederik Palm; Johansen, Christoffer; Kessing, Lars Vedel

2017-01-01

treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer-specific survival, and risk of death by suicide of women who were and were not treated for depression before......Purpose The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival. Material...... and Methods We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous...

Microaspiration of esophageal gland cells and cDNA library construction for identifying parasitism genes of plant-parasitic nematodes.

Science.gov (United States)

Hussey, Richard S; Huang, Guozhong; Allen, Rex

2011-01-01

Identifying parasitism genes encoding proteins secreted from a plant-parasitic nematode's esophageal gland cells and injected through its stylet into plant tissue is the key to understanding the molecular basis of nematode parasitism of plants. Parasitism genes have been cloned by directly microaspirating the cytoplasm from the esophageal gland cells of different parasitic stages of cyst or root-knot nematodes to provide mRNA to create a gland cell-specific cDNA library by long-distance reverse-transcriptase polymerase chain reaction. cDNA clones are sequenced and deduced protein sequences with a signal peptide for secretion are identified for high-throughput in situ hybridization to confirm gland-specific expression.

Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

Science.gov (United States)

Bennuru, Sasisekhar; Cotton, James A.; Ribeiro, Jose M. C.; Grote, Alexandra; Harsha, Bhavana; Holroyd, Nancy; Mhashilkar, Amruta; Molina, Douglas M.; Randall, Arlo Z.; Shandling, Adam D.; Unnasch, Thomas R.; Ghedin, Elodie; Berriman, Matthew

2016-01-01

ABSTRACT Onchocerciasis (river blindness) is a neglected tropical disease that has been successfully targeted by mass drug treatment programs in the Americas and small parts of Africa. Achieving the long-term goal of elimination of onchocerciasis, however, requires additional tools, including drugs, vaccines, and biomarkers of infection. Here, we describe the transcriptome and proteome profiles of the major vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and adult female) of Onchocerca volvulus along with the proteome of each parasitic stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified stage-specific pathways important to the parasite’s adaptation to its human host during its early development. Further, we generated a protein array that, when screened with well-characterized human samples, identified novel diagnostic biomarkers of O. volvulus infection and new potential vaccine candidates. This immunomic approach not only demonstrates the power of this postgenomic discovery platform but also provides additional tools for onchocerciasis control programs. PMID:27881553

Signalling in malaria parasites. The MALSIG consortium.

NARCIS (Netherlands)

Doerig, C.; Baker, D.; Billker, O.; Blackman, M.J.; Chitnis, C.; Dhar Kumar, S.; Heussler, V.; Holder, A.A.; Kocken, C.; Krishna, S.; Langsley, G.; Lasonder, E.; Menard, R.; Meissner, M.; Pradel, G.; Ranford-Cartwright, L.; Sharma, A.; Sharma, P.; Tardieux, T.; Tatu, U.; Alano, P.

2009-01-01

Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense

Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy

International Nuclear Information System (INIS)

Chan, Alexander K.P.; Wong, Alfred; Jenken, Daryl; Heine, John; Buie, Donald; Johnson, Douglas

2005-01-01

Purpose: To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy. Methods and materials: Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m 2 /d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m 2 ) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system. Results: Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically significant

Deception and Manipulation: The Arms of Leishmania, a Successful Parasite

Science.gov (United States)

Cecílio, Pedro; Pérez-Cabezas, Begoña; Santarém, Nuno; Maciel, Joana; Rodrigues, Vasco; Cordeiro da Silva, Anabela

2014-01-01

Leishmania spp. are intracellular parasitic protozoa responsible for a group of neglected tropical diseases, endemic in 98 countries around the world, called leishmaniasis. These parasites have a complex digenetic life cycle requiring a susceptible vertebrate host and a permissive insect vector, which allow their transmission. The clinical manifestations associated with leishmaniasis depend on complex interactions between the parasite and the host immune system. Consequently, leishmaniasis can be manifested as a self-healing cutaneous affliction or a visceral pathology, being the last one fatal in 85–90% of untreated cases. As a result of a long host–parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection. Only through deception and manipulation of the immune system, Leishmania spp. can complete its life cycle and survive. The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches. Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system. PMID:25368612

Deception and Manipulation: the arms of Leishmania, a successful parasite

Directory of Open Access Journals (Sweden)

Pedro eCecílio

2014-10-01

Full Text Available Leishmania spp. are intracellular parasitic protozoa responsible for a group of neglected tropical diseases, endemic in 98 countries around the world, called leishmaniasis. These parasites have a complex digenetic life cycle requiring a susceptible vertebrate host and a permissive insect vector, which allow their transmission. The clinical manifestations associated with leishmaniasis depend on complex interactions between the parasite and the host immune system. Consequently, leishmaniasis can be manifested as a self-healing cutaneous affliction or a visceral pathology, being the last one fatal in 85-90% of untreated cases. As a result of a long host-parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection. Only through deception and manipulation of the immune system, Leishmania spp. can complete its life cycle and survive. The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches. Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system.

Adherence to treatment guidelines and survival for older patients with stage II or III colon cancer in Texas from 2001 through 2011.

Science.gov (United States)

Zhao, Hui; Zhang, Ning; Ho, Vivian; Ding, Minming; He, Weiguo; Niu, Jiangong; Yang, Ming; Du, Xianglin L; Zorzi, Daria; Chavez-MacGregor, Mariana; Giordano, Sharon H

2018-02-15

Treatment guidelines for colon cancer recommend colectomy with lymphadenectomy of at least 12 lymph nodes for patients with stage I to stage III disease as surgery adherence (SA) and adjuvant chemotherapy for individuals with stage III disease. Herein, the authors evaluated adherence to these guidelines among older patients in Texas with colon cancer and the associated survival outcomes. Using Texas Cancer Registry data linked with Medicare data, the authors included patients with AJCC stage II and III colon cancer who were aged ≥66 years and diagnosed between 2001 and 2011. SA and adjuvant chemotherapy adherence rates to treatment guidelines were estimated. The chi-square test, general linear regression, survival probability, and Cox regression were used to identify factors associated with adherence and survival. The rate of SA increased from 47.2% to 84% among 6029 patients with stage II or stage III disease from 2001 to 2011, and the rate of adjuvant chemotherapy increased from 48.9% to 53.1% for patients with stage III disease during the same time period. SA was associated with marital status, tumor size, surgeon specialty, and year of diagnosis. Patient age, sex, marital status, Medicare state buy-in status, comorbidity status, and year of diagnosis were found to be associated with adjuvant chemotherapy. The 5-year survival probability for patients receiving guideline-concordant treatment was the highest at 87% for patients with stage II disease and was 73% for those with stage III disease. After adjusting for demographic and tumor characteristics, improved cancer cause-specific survival was associated with the receipt of stage-specific, guideline-concordant treatment for patients with stage II or stage III disease. The adherence to guideline-concordant treatment among older patients with colon cancer residing in Texas improved over time, and was associated with better survival outcomes. Future studies should be focused on identifying interventions to

Leishmania development in sand flies: parasite-vector interactions overview.

Science.gov (United States)

Dostálová, Anna; Volf, Petr

2012-12-03

Leishmaniases are vector-borne parasitic diseases with 0.9 - 1.4 million new human cases each year worldwide. In the vectorial part of the life-cycle, Leishmania development is confined to the digestive tract. During the first few days after blood feeding, natural barriers to Leishmania development include secreted proteolytic enzymes, the peritrophic matrix surrounding the ingested blood meal and sand fly immune reactions. As the blood digestion proceeds, parasites need to bind to the midgut epithelium to avoid being excreted with the blood remnant. This binding is strictly stage-dependent as it is a property of nectomonad and leptomonad forms only. While the attachment in specific vectors (P. papatasi, P. duboscqi and P. sergenti) involves lipophosphoglycan (LPG), this Leishmania molecule is not required for parasite attachment in other sand fly species experimentally permissive for various Leishmania. During late-stage infections, large numbers of parasites accumulate in the anterior midgut and produce filamentous proteophosphoglycan creating a gel-like plug physically obstructing the gut. The parasites attached to the stomodeal valve cause damage to the chitin lining and epithelial cells of the valve, interfering with its function and facilitating reflux of parasites from the midgut. Transformation to metacyclic stages highly infective for the vertebrate host is the other prerequisite for effective transmission. Here, we review the current state of knowledge of molecular interactions occurring in all these distinct phases of parasite colonization of the sand fly gut, highlighting recent discoveries in the field.

Stearoyl-CoA desaturase is an essential enzyme for the parasitic protist Trypanosoma brucei

Energy Technology Data Exchange (ETDEWEB)

Alloatti, Andres [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Gupta, Shreedhara; Gualdron-Lopez, Melisa; Nguewa, Paul A. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Altabe, Silvia G. [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina); Deumer, Gladys; Wallemacq, Pierre [Department of Clinical Chemistry, Cliniques Universitaires Saint-Luc, LTAP, Universite Catholique de Louvain, Brussels (Belgium); Michels, Paul A.M. [Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Universite Catholique de Louvain, Brussels (Belgium); Uttaro, Antonio D., E-mail: toniuttaro@yahoo.com.ar [Instituto de Biologia Molecular y Celular de Rosario (IBR), CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Santa Fe (Argentina)

2011-08-26

Highlights: {yields} Inhibiting {Delta}9 desaturase drastically changes T. brucei's fatty-acid composition. {yields} Isoxyl specifically inhibits the {Delta}9 desaturase causing a growth arrest. {yields} RNA interference of desaturase expression causes a similar effect. {yields} Feeding T. brucei-infected mice with Isoxyl decreases the parasitemia. {yields} 70% of Isoxyl-treated mice survived the trypanosome infection. -- Abstract: Trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. To adapt to these changes, the fluidity of its membranes plays a crucial role. This fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. We have previously shown that the oleoyl desaturase is essential for Trypanosoma cruzi and T. brucei. In this work, we present experimental support for the relevance of stearoyl-CoA desaturase (SCD) for T. brucei's survival, in both its insect or procyclic-form (PCF) and bloodstream-form (BSF) stages. We evaluated this essentiality in two different ways: by generating a SCD knocked-down parasite line using RNA interference, and by chemical inhibition of the enzyme with two compounds, Isoxyl and a thiastearate with the sulfur atom at position 10 (10-TS). The effective concentration for 50% growth inhibition (EC{sub 50}) of PCF was 1.0 {+-} 0.2 {mu}M for Isoxyl and 5 {+-} 2 {mu}M for 10-TS, whereas BSF appeared more susceptible with EC{sub 50} values 0.10 {+-} 0.03 {mu}M (Isoxyl) and 1.0 {+-} 0.6 {mu}M (10-TS). RNA interference showed to be deleterious for both stages of the parasite. In addition, T. brucei-infected mice were fed with Isoxyl, causing a reduction of the parasitemia and an increase of the rodents' survival.

Stearoyl-CoA desaturase is an essential enzyme for the parasitic protist Trypanosoma brucei

International Nuclear Information System (INIS)

Alloatti, Andres; Gupta, Shreedhara; Gualdron-Lopez, Melisa; Nguewa, Paul A.; Altabe, Silvia G.; Deumer, Gladys; Wallemacq, Pierre; Michels, Paul A.M.; Uttaro, Antonio D.

2011-01-01

Highlights: → Inhibiting Δ9 desaturase drastically changes T. brucei's fatty-acid composition. → Isoxyl specifically inhibits the Δ9 desaturase causing a growth arrest. → RNA interference of desaturase expression causes a similar effect. → Feeding T. brucei-infected mice with Isoxyl decreases the parasitemia. → 70% of Isoxyl-treated mice survived the trypanosome infection. -- Abstract: Trypanosoma brucei, the etiologic agent of sleeping sickness, is exposed to important changes in nutrients and temperature during its life cycle. To adapt to these changes, the fluidity of its membranes plays a crucial role. This fluidity, mediated by the fatty-acid composition, is regulated by enzymes named desaturases. We have previously shown that the oleoyl desaturase is essential for Trypanosoma cruzi and T. brucei. In this work, we present experimental support for the relevance of stearoyl-CoA desaturase (SCD) for T. brucei's survival, in both its insect or procyclic-form (PCF) and bloodstream-form (BSF) stages. We evaluated this essentiality in two different ways: by generating a SCD knocked-down parasite line using RNA interference, and by chemical inhibition of the enzyme with two compounds, Isoxyl and a thiastearate with the sulfur atom at position 10 (10-TS). The effective concentration for 50% growth inhibition (EC 50 ) of PCF was 1.0 ± 0.2 μM for Isoxyl and 5 ± 2 μM for 10-TS, whereas BSF appeared more susceptible with EC 50 values 0.10 ± 0.03 μM (Isoxyl) and 1.0 ± 0.6 μM (10-TS). RNA interference showed to be deleterious for both stages of the parasite. In addition, T. brucei-infected mice were fed with Isoxyl, causing a reduction of the parasitemia and an increase of the rodents' survival.

Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival.

Directory of Open Access Journals (Sweden)

Miriam A Lynn

Full Text Available Protozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28 has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28 and the retro-inverso form (RI-BMAP-28, as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages.An MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model.Interestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant isomers have significant therapeutic potential as novel anti-leishmanials.

Perioperative Outcomes and Long-term Survival in Clinically Early-stage Thymic 
Malignancies: Video-assisted Thoracoscopic Thymectomy versus Open Approaches

Directory of Open Access Journals (Sweden)

Hao WANG

2016-07-01

Full Text Available Background and objective Video-assisted thoracoscopic surgery (VATS theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II thymic malignancies. However, longterm outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART. Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group, while 876 cases underwent open thymectomy (Open group. Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs 73.9%, P=0.028, resection rate (98.8% vs 88.7%, P<0.001 and less recurrence (2.9% vs 16.0%, P<0.001. Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15. However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011. Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusion This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival.

Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

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Anthony, Winston E; Palmer-Young, Evan C; Leonard, Anne S; Irwin, Rebecca E; Adler, Lynn S

2015-01-01

The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees.

Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

Directory of Open Access Journals (Sweden)

Winston E Anthony

Full Text Available The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees.

The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction

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Hussein, Hala E.; Bastos, Reginaldo G.; Schneider, David A.; Johnson, Wendell C.; Adham, Fatma K.; Davis, William C.; Laughery, Jacob M.; Herndon, David R.; Alzan, Heba F.

2017-01-01

Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. Expression of HAP2 has been recognized as critical for the fertilization of parasites in the Babesia-related Plasmodium, and is a leading candidate for a transmission blocking vaccine against malaria. Hereby we identified the B. bovis hap2 gene and demonstrated that it is widely conserved and differentially transcribed during development within the tick midgut, but not by blood stage parasites. The hap2 gene was disrupted by transfecting B. bovis with a plasmid containing the flanking regions of the hap2 gene and the GPF-BSD gene under the control of the ef-1α-B promoter. Comparison of in vitro growth between a hap2-KO B. bovis clonal line and its parental wild type strain showed that HAP2 is not required for the development of B. bovis in erythrocytes. However, xanthurenic acid-in vitro induction experiments of sexual stages of parasites recovered after tick transmission resulted in surface expression of HAP2 exclusively in sexual stage induced parasites. In addition, hap2-KO parasites were not able to develop such sexual stages as defined both by morphology and by expression of the B. bovis sexual marker genes 6-Cys A and B. Together, the data strongly suggests that tick midgut stage differential expression of hap2 is associated with the development of B. bovis sexual forms. Overall these studies are consistent with a role of HAP2 in tick stages of the parasite and suggest that HAP2 is a potential candidate for a transmission blocking vaccine against bovine babesiosis. PMID:28985216

A nomogram to predict the survival of stage IIIA-N2 non-small cell lung cancer after surgery.

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Mao, Qixing; Xia, Wenjie; Dong, Gaochao; Chen, Shuqi; Wang, Anpeng; Jin, Guangfu; Jiang, Feng; Xu, Lin

2018-04-01

Postoperative survival of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is highly heterogeneous. Here, we aimed to identify variables associated with postoperative survival and develop a tool for survival prediction. A retrospective review was performed in the Surveillance, Epidemiology, and End Results database from January 2004 to December 2009. Significant variables were selected by use of the backward stepwise method. The nomogram was constructed with multivariable Cox regression. The model's performance was evaluated by concordance index and calibration curve. The model was validated via an independent cohort from the Jiangsu Cancer Hospital Lung Cancer Center. A total of 1809 patients with stage IIIA-N2 NSCLC who underwent surgery were included in the training cohort. Age, sex, grade, histology, tumor size, visceral pleural invasion, positive lymph nodes, lymph nodes examined, and surgery type (lobectomy vs pneumonectomy) were identified as significant prognostic variables using backward stepwise method. A nomogram was developed from the training cohort and validated using an independent Chinese cohort. The concordance index of the model was 0.673 (95% confidence interval, 0.654-0.692) in training cohort and 0.664 in validation cohort (95% confidence interval, 0.614-0.714). The calibration plot showed optimal consistency between nomogram predicted survival and observed survival. Survival analyses demonstrated significant differences between different subgroups stratified by prognostic scores. This nomogram provided the individual survival prediction for patients with stage IIIA-N2 NSCLC after surgery, which might benefit survival counseling for patients and clinicians, clinical trial design and follow-up, as well as postoperative strategy-making. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites.

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Delves, Michael; Plouffe, David; Scheurer, Christian; Meister, Stephan; Wittlin, Sergio; Winzeler, Elizabeth A; Sinden, Robert E; Leroy, Didier

2012-02-01

Malaria remains a disease of devastating global impact, killing more than 800,000 people every year-the vast majority being children under the age of 5. While effective therapies are available, if malaria is to be eradicated a broader range of small molecule therapeutics that are able to target the liver and the transmissible sexual stages are required. These new medicines are needed both to meet the challenge of malaria eradication and to circumvent resistance. Little is known about the wider stage-specific activities of current antimalarials that were primarily designed to alleviate symptoms of malaria in the blood stage. To overcome this critical gap, we developed assays to measure activity of antimalarials against all life stages of malaria parasites, using a diverse set of human and nonhuman parasite species, including male gamete production (exflagellation) in Plasmodium falciparum, ookinete development in P. berghei, oocyst development in P. berghei and P. falciparum, and the liver stage of P. yoelii. We then compared 50 current and experimental antimalarials in these assays. We show that endoperoxides such as OZ439, a stable synthetic molecule currently in clinical phase IIa trials, are strong inhibitors of gametocyte maturation/gamete formation and impact sporogony; lumefantrine impairs development in the vector; and NPC-1161B, a new 8-aminoquinoline, inhibits sporogony. These data enable objective comparisons of the strengths and weaknesses of each chemical class at targeting each stage of the lifecycle. Noting that the activities of many compounds lie within achievable blood concentrations, these results offer an invaluable guide to decisions regarding which drugs to combine in the next-generation of antimalarial drugs. This study might reveal the potential of life-cycle-wide analyses of drugs for other pathogens with complex life cycles.

The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites

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Delves, Michael; Plouffe, David; Scheurer, Christian; Meister, Stephan; Wittlin, Sergio; Winzeler, Elizabeth A.; Sinden, Robert E.; Leroy, Didier

2012-01-01

Background Malaria remains a disease of devastating global impact, killing more than 800,000 people every year—the vast majority being children under the age of 5. While effective therapies are available, if malaria is to be eradicated a broader range of small molecule therapeutics that are able to target the liver and the transmissible sexual stages are required. These new medicines are needed both to meet the challenge of malaria eradication and to circumvent resistance. Methods and Findings Little is known about the wider stage-specific activities of current antimalarials that were primarily designed to alleviate symptoms of malaria in the blood stage. To overcome this critical gap, we developed assays to measure activity of antimalarials against all life stages of malaria parasites, using a diverse set of human and nonhuman parasite species, including male gamete production (exflagellation) in Plasmodium falciparum, ookinete development in P. berghei, oocyst development in P. berghei and P. falciparum, and the liver stage of P. yoelii. We then compared 50 current and experimental antimalarials in these assays. We show that endoperoxides such as OZ439, a stable synthetic molecule currently in clinical phase IIa trials, are strong inhibitors of gametocyte maturation/gamete formation and impact sporogony; lumefantrine impairs development in the vector; and NPC-1161B, a new 8-aminoquinoline, inhibits sporogony. Conclusions These data enable objective comparisons of the strengths and weaknesses of each chemical class at targeting each stage of the lifecycle. Noting that the activities of many compounds lie within achievable blood concentrations, these results offer an invaluable guide to decisions regarding which drugs to combine in the next-generation of antimalarial drugs. This study might reveal the potential of life-cycle–wide analyses of drugs for other pathogens with complex life cycles. Please see later in the article for the Editors' Summary PMID

Survival, reproduction, growth, and parasite resistance of aquatic organisms exposed on-site to wastewater treated by advanced treatment processes.

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Schlüter-Vorberg, Lisa; Knopp, Gregor; Cornel, Peter; Ternes, Thomas; Coors, Anja

2017-05-01

Advanced wastewater treatment technologies are generally known to be an effective tool for reducing micropollutant discharge into the aquatic environment. Nevertheless, some processes such as ozonation result in stable transformation products with often unknown toxicity. In the present study, whole effluents originating from nine different steps of advanced treatment combinations were compared for their aquatic toxicity. Assessed endpoints were survival, growth and reproduction of Lumbriculus variegatus, Daphnia magna and Lemna minor chronically exposed in on-site flow-through tests based on standard guidelines. The treatment combinations were activated sludge treatment followed by ozonation with subsequent filtration by granular activated carbon or biofilters and membrane bioreactor treatment of raw wastewater followed by ozonation. Additionally, the impact of treated wastewater on the immune response of invertebrates was investigated by challenging D. magna with a bacterial endoparasite. Conventionally treated wastewater reduced reproduction of L. variegatus by up to 46%, but did not affect D. magna and L. minor with regard to survival, growth, reproduction and parasite resistance. Instead, parasite susceptibility was significantly reduced in D. magna exposed to conventionally treated as well as ozonated wastewater in comparison to D. magna exposed to the medium control. None of the three test organisms provided clear evidence that wastewater ozonation leads to increased aquatic toxicity. Rather than to the presence of toxic transformation products, the affected performance of L. variegatus could be linked to elevated concentrations of ammonium and nitrite that likely resulted from treatment failures. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental infection and transmission of Leishmania by Lutzomyia cruzi (Diptera: Psychodidae: Aspects of the ecology of parasite-vector interactions.

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Everton Falcão de Oliveira

2017-02-01

Full Text Available Several parameters should be addressed before incriminating a vector for Leishmania transmission. Those may include its ability to become infected by the same Leishmania species found in humans, the degree of attractiveness for reservoirs and humans and capacity to sustain parasite infection under laboratory conditions. This study evaluated the vectorial capacity of Lutzomyia cruzi for Leishmania infantum and gathered information on its ability to harbor L. amazonensis. Laboratory-reared Lu. cruzi were infected experimentally by feeding them on dogs infected naturally with L. infantum and hamsters infected with L. amazonensis. Sand fly attractiveness to dogs and humans was determined using wild caught insects. The expected daily survival of infected Lu. cruzi, the duration of the gonotrophic cycle, and the extrinsic incubation period were also investigated for both parasites. Vector competence was investigated for both Leishmania species. The mean proportion of female sand flies that fed on hosts was 0.40. For L. infantum and L. amazonensis, Lu. cruzi had experimental infection rates of 10.55% and 41.56%, respectively. The extrinsic incubation period was 3 days for both Leishmania species, regardless of the host. Survival expectancy of females infected with L. infantum and L. amazonensis after completing the gonotrophic cycle was 1.32 and 0.43, respectively. There was no association between L. infantum infection and sand fly longevity, but L. amazonensis-infected flies had significantly greater survival probabilities. Furthermore, egg-laying was significantly detrimental to survival. Lu. cruzi was found to be highly attracted to both dogs and humans. After a bloodmeal on experimentally infected hosts, both parasites were able to survive and develop late-stage infections in Lu. cruzi. However, transmission was demonstrated only for L. amazonensis-infected sand flies. In conclusion, Lu. cruzi fulfilled several of the requirements of vectorial

Experimental infection and transmission of Leishmania by Lutzomyia cruzi (Diptera: Psychodidae): Aspects of the ecology of parasite-vector interactions.

Science.gov (United States)

Falcão de Oliveira, Everton; Oshiro, Elisa Teruya; Fernandes, Wagner de Souza; Murat, Paula Guerra; Medeiros, Márcio José de; Souza, Alda Izabel; Oliveira, Alessandra Gutierrez de; Galati, Eunice Aparecida Bianchi

2017-02-01

Several parameters should be addressed before incriminating a vector for Leishmania transmission. Those may include its ability to become infected by the same Leishmania species found in humans, the degree of attractiveness for reservoirs and humans and capacity to sustain parasite infection under laboratory conditions. This study evaluated the vectorial capacity of Lutzomyia cruzi for Leishmania infantum and gathered information on its ability to harbor L. amazonensis. Laboratory-reared Lu. cruzi were infected experimentally by feeding them on dogs infected naturally with L. infantum and hamsters infected with L. amazonensis. Sand fly attractiveness to dogs and humans was determined using wild caught insects. The expected daily survival of infected Lu. cruzi, the duration of the gonotrophic cycle, and the extrinsic incubation period were also investigated for both parasites. Vector competence was investigated for both Leishmania species. The mean proportion of female sand flies that fed on hosts was 0.40. For L. infantum and L. amazonensis, Lu. cruzi had experimental infection rates of 10.55% and 41.56%, respectively. The extrinsic incubation period was 3 days for both Leishmania species, regardless of the host. Survival expectancy of females infected with L. infantum and L. amazonensis after completing the gonotrophic cycle was 1.32 and 0.43, respectively. There was no association between L. infantum infection and sand fly longevity, but L. amazonensis-infected flies had significantly greater survival probabilities. Furthermore, egg-laying was significantly detrimental to survival. Lu. cruzi was found to be highly attracted to both dogs and humans. After a bloodmeal on experimentally infected hosts, both parasites were able to survive and develop late-stage infections in Lu. cruzi. However, transmission was demonstrated only for L. amazonensis-infected sand flies. In conclusion, Lu. cruzi fulfilled several of the requirements of vectorial capacity for L. infantum

Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

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Mohan, H M; Ryan, E; Balasubramanian, I; Kennelly, R; Geraghty, R; Sclafani, F; Fennelly, D; McDermott, R; Ryan, E J; O'Donoghue, D; Hyland, J M P; Martin, S T; O'Connell, P R; Gibbons, D; Winter, Des; Sheahan, K

2016-11-01

Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes. Copyright © 2016. Published by Elsevier Ltd.

Different patterns in the prognostic value of age for bladder cancer-specific survival depending on tumor stages.

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Feng, Huan; Zhang, Wei; Li, Jiajun; Lu, Xiaozhe

2015-01-01

To compare the pathological features and long-term survival of bladder cancer (BCa) in young patients with elderly counterparts. Using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 93115 patients with non-metastatic bladder cancer diagnosed between 1988 and 2003. Patients were categorized into young (50 years and under) and elderly groups (over 50 years of age). The overall and five-year bladder cancer specific survival (BCSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in primary site, pathologic grading, histologic type, AJCC stage (pstage patients. The study findings show different patterns in the prognostic value of age for determining BCSS, depending on the tumor stages. Compared with elderly patients, young patients with bladder cancer surgery appear to have unique characteristics and a higher overall and cancer specific survival rate.

Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Wang, Chia-Chun; Cheng, Jason Chia-Hsien; Tsai, Chiao-Ling; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Hsieh, Min-Shu; Chang, Yih-Leong; Hsu, Feng-Ming

2015-01-01

Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

Serine protease inhibitors of parasitic helminths.

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Molehin, Adebayo J; Gobert, Geoffrey N; McManus, Donald P

2012-05-01

Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.

Practice patterns and long-term survival for early-stage rectal cancer.

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Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Mixed adenosquamous histology is associated with poorer survival of cervical cancer stage 1b

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Lauszus, Finn; Tjessem, Ingvild; Al-Far, Hanine M

2016-01-01

Background: Evaluation of histopathological factors for women with radical hysterectomy a.m. Okabayashi for cervical cancer in stage 1bwith similar pre- and postoperative treatment Methods: Data on 141 women with cervical cancer stage 1b were revised. The local patient registry, data charts...... and adenomatous type (pmixed versus pure type). Five year’s survival rate was 40 % (2-78 %) for mixed type and 92 % (87-97 %) for pure type. The mixed type was associated with glandular metastasis (p

Age-specific haemosporidian infection dynamics and survival in Seychelles warblers

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Hammers, Martijn; Komdeur, Jan; Kingma, Sjouke A.; Hutchings, Kimberly; Fairfield, Eleanor A.; Gilroy, Danielle L.; Richardson, David S.

2016-01-01

Parasites may severely impact the fitness and life-history of their hosts. After infection, surviving individuals may suppress the growth of the parasite, or completely clear the infection and develop immunity. Consequently, parasite prevalence is predicted to decline with age. Among elderly individuals, immunosenescence may lead to a late-life increase in infection prevalence. We used a 21-year longitudinal dataset from one population of individually-marked Seychelles warblers (Acrocephalus sechellensis) to investigate age-dependent prevalence of the GRW1 strain of the intracellular protozoan blood parasite Haemoproteus nucleocondensus and whether infections with this parasite affect age-dependent survival. We analyzed 2454 samples from 1431 individuals and found that H. nucleocondensus infections could rarely be detected in nestlings. Prevalence increased strongly among fledglings and peaked among older first year birds. Prevalence was high among younger adults and declined steeply until ca 4 years of age, after which it was stable. Contrary to expectations, H. nucleocondensus prevalence did not increase among elderly individuals and we found no evidence that annual survival was lower in individuals suffering from an infection. Our results suggest that individuals clear or suppress infections and acquire immunity against future infections, and provide no evidence for immunosenescence nor an impact of chronic infections on survival. PMID:27431430

Genetic variation in anti-parasite behavior in oysters

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Behavioral avoidance of disease-causing parasites provides a first line of defense against the threat of infection, particularly when hosts are exposed to free-living parasite stages in the external environment. We report that suspension-feeding oysters (Crassostrea virginica) respond to the presenc...

Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

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Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

2015-01-01

. Data on patients with stage III colonic cancer operated between January 1, 2005 and August 31, 2012 were retrieved. Perioperative variables, surgical modality, and time to adjuvant therapy (8 weeks) were evaluated and Cox regression was performed to identify factors influencing survival...

Transport proteins of parasitic protists and their role in nutrient salvage.

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Dean, Paul; Major, Peter; Nakjang, Sirintra; Hirt, Robert P; Embley, T Martin

2014-01-01

The loss of key biosynthetic pathways is a common feature of important parasitic protists, making them heavily dependent on scavenging nutrients from their hosts. This is often mediated by specialized transporter proteins that ensure the nutritional requirements of the parasite are met. Over the past decade, the completion of several parasite genome projects has facilitated the identification of parasite transporter proteins. This has been complemented by functional characterization of individual transporters along with investigations into their importance for parasite survival. In this review, we summarize the current knowledge on transporters from parasitic protists and highlight commonalities and differences in the transporter repertoires of different parasitic species, with particular focus on characterized transporters that act at the host-pathogen interface.

Urbanization breaks up host-parasite interactions: a case study on parasite community ecology of rufous-bellied thrushes (Turdus rufiventris) along a rural-urban gradient.

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Calegaro-Marques, Cláudia; Amato, Suzana B

2014-01-01

Urbanization drastically alters natural ecosystems and the structure of their plant and animal communities. Whereas some species cope successfully with these environmental changes, others may go extinct. In the case of parasite communities, the expansion of urban areas has a critical effect by changing the availability of suitable substrates for the eggs or free-larval stages of those species with direct life cycles or for the range of hosts of those species with complex cycles. In this study we investigated the influence of the degree of urbanization and environmental heterogeneity on helminth richness, abundance and community structure of rufous-bellied thrushes (Turdus rufiventris) along a rural-urban gradient in the metropolitan region of Porto Alegre, State of Rio Grande do Sul, Brazil. This common native bird species of southern Brazil hosts 15 endoparasite species at the study region. A total of 144 thrushes were collected with mist nets at 11 sites. The degree of urbanization and environmental heterogeneity were estimated by quantifying five landscape elements: buildings, woodlands, fields, bare lands, and water. Landscape analyses were performed at two spatial scales (10 and 100 ha) taking into account home range size and the potential dispersal distance of thrushes and their prey (intermediate hosts). Mean parasite richness showed an inverse relationship with the degree of urbanization, but a positive relationship with environmental heterogeneity. Changes in the structure of component communities along the rural-urban gradient resulted from responses to the availability of particular landscape elements that are compatible with the parasites' life cycles. We found that the replacement of natural environments with buildings breaks up host-parasite interactions, whereas a higher environmental (substrate) diversity allows the survival of a wider range of intermediate hosts and vectors and their associated parasites.

Fitness of Leishmania donovani parasites resistant to drug combinations.

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Raquel García-Hernández

2015-04-01

Full Text Available Drug resistance represents one of the main problems for the use of chemotherapy to treat leishmaniasis. Additionally, it could provide some advantages to Leishmania parasites, such as a higher capacity to survive in stress conditions. In this work, in mixed populations of Leishmania donovani parasites, we have analyzed whether experimentally resistant lines to one or two combined anti-leishmanial drugs better support the stress conditions than a susceptible line expressing luciferase (Luc line. In the absence of stress, none of the Leishmania lines showed growth advantage relative to the other when mixed at a 1:1 parasite ratio. However, when promastigotes from resistant lines and the Luc line were mixed and exposed to different stresses, we observed that the resistant lines are more tolerant of different stress conditions: nutrient starvation and heat shock-pH stress. Further to this, we observed that intracellular amastigotes from resistant lines present a higher capacity to survive inside the macrophages than those of the control line. These results suggest that resistant parasites acquire an overall fitness increase and that resistance to drug combinations presents significant differences in their fitness capacity versus single-drug resistant parasites, particularly in intracellular amastigotes. These results contribute to the assessment of the possible impact of drug resistance on leishmaniasis control programs.

Validation of the CPS + EG Staging System for Disease-Specific Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

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Abdelsattar, Jad M; Al-Hilli, Zahraa; Hoskin, Tanya L; Heins, Courtney N; Boughey, Judy C

2016-10-01

CPS + EG staging, which incorporates estrogen receptor (ER) status and tumor grade with pretreatment clinical stage (CS) and post-treatment pathologic stage (PS), has been reported to have better correlation with outcome than classic TNM staging for patients treated with neoadjuvant chemotherapy (NAC). Our goal was to evaluate the performance of CPS + EG staging system in an external cohort treated with NAC. We reviewed patients with stages I-IIIC breast cancer treated with NAC and surgery at our institution between 1988 and 2014. ER status, Nottingham grade, treatment, American Joint Committee on Cancer (AJCC) CS before NAC and PS after NAC, and follow-up data were collected. The discrimination of CPS + EG and pathologic AJCC stage were assessed using area under the curve (AUC) for survival data. A total of 769 patients were analyzed with a median follow-up of 2.6 (range 0.0-19.4) years; 103 patients died of breast cancer. Overall, the 5-year breast cancer cause-specific survival was 81.5 % [95 % confidence interval (CI) 77.6-85.5]. The 5-year, cause-specific survival by CPS + EG score was 93.8 % score 0, 89.9 % score 1, 90.7 % score 2, 84.8 % score 3, 67.7 % score 4, and 43.4 % score 5/6. CPS + EG score was significantly associated with cause-specific survival (p < 0.001) with an AUC of 0.69 (95 % CI 0.62-0.77) at 5 years. This was higher than the AUC of 0.63 (95 % CI 0.56-0.70) for AJCC PS (p = 0.10). This study validates the CPS + EG staging system using Nottingham grade in an external cohort. Addition of tumor biology and treatment response shows promise in improving survival estimates for patients treated with NAC.

The adaptive significance of inquiline parasite workers

DEFF Research Database (Denmark)

Sumner, Seirian; Nash, David R; Boomsma, Jacobus J

2003-01-01

Social parasites exploit the socially managed resources of their host's society. Inquiline social parasites are dependent on their host throughout their life cycle, and so many of the traits inherited from their free-living ancestor are removed by natural selection. One trait that is commonly lost...... is the worker caste, the functions of which are adequately fulfilled by host workers. The few inquiline parasites that have retained a worker caste are thought to be at a transitional stage in the evolution of social parasitism, and their worker castes are considered vestigial and non-adaptive. However...... a vital role in ensuring the parasite's fitness. We show that the presence of these parasite workers has a positive effect on the production of parasite sexuals and a negative effect on the production of host sexuals. This suggests that inquiline workers play a vital role in suppressing host queen...

Interglacial insects and their possible survival in Greenland during the last glacial stage

DEFF Research Database (Denmark)

Bøcher, Jens Jensenius

2012-01-01

Sediments from the last interglacial (Eemian) in Jameson Land, East Greenland, and the Thule area, NW Greenland, have revealed a number of insect fragments of both arctic and more or less warmth-demanding species. Altogether, the interglacial fauna of Coleoptera (beetles) indicates boreal...... beetle species such as Amara alpina and Isochnus arcticus did not survive the last glacial stage in Greenland. Two factors that have not been sufficiently considered when discussing survival contra extinction are the importance of microclimate and the number of sun-hours during the Arctic summer. Even...... among the Coleoptera, which as a group fares quite badly in the Arctic, there might be survivors, at least among those found both during the interglacial and as fossils during the early Holocene. First of all, glacial survival applies to the seed bug Nysius groenlandicus, which was widespread during...

Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study.

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Elshaikh, Mohamed A; Ruterbusch, Julie; Cote, Michele L; Cattaneo, Richard; Munkarah, Adnan R

2013-11-01

To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC). Data were obtained from the SEER registry between 1988-2009. Inclusion criteria included women who underwent hysterectomy for stage I-II EC. Patients were divided into two birth cohorts: BB (women born between 1946 and 1964) and pre-boomers (PB) (born between 1926 and 1945). A total of 30,956 patients were analyzed. Considering that women in the PB group were older than those of the BB generation, the statistical analysis was limited to women 50-59 years of age at the time of diagnosis (n=11,473). Baby boomers had a significantly higher percentage of endometrioid histology (pgeneration compared to the PB generation (p=0.0003) with a trend for improved uterine cancer-specific survival (p=0.0752). On multivariate analysis, birth cohort (BB vs. PB) was not a significant predictor of survival end-points. Factors predictive of survival included: tumor grade, FIGO stage, African-American race, and increased number of dissected LN. Our study suggests that the survival of BB women between 50-60 years of age is better compared to women in the PB generation. As more BB patients are diagnosed with EC, further research is warranted.

Regional variations in cancer survival: Impact of tumour stage, socioeconomic status, comorbidity and type of treatment in Norway.

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Skyrud, Katrine Damgaard; Bray, Freddie; Eriksen, Morten Tandberg; Nilssen, Yngvar; Møller, Bjørn

2016-05-01

Cancer survival varies by place of residence, but it remains uncertain whether this reflects differences in tumour, patient and treatment characteristics (including tumour stage, indicators of socioeconomic status (SES), comorbidity and information on received surgery and radiotherapy) or possibly regional differences in the quality of delivered health care. National population-based data from the Cancer Registry of Norway were used to identify cancer patients diagnosed in 2002-2011 (n = 258,675). We investigated survival from any type of cancer (all cancer sites combined), as well as for the six most common cancers. The effect of adjusting for prognostic factors on regional variations in cancer survival was examined by calculating the mean deviation, defined by the mean absolute deviation of the relative excess risks across health services regions. For prostate cancer, the mean deviation across regions was 1.78 when adjusting for age and sex only, but decreased to 1.27 after further adjustment for tumour stage. For breast cancer, the corresponding mean deviations were 1.34 and 1.27. Additional adjustment for other prognostic factors did not materially change the regional variation in any of the other sites. Adjustment for tumour stage explained most of the regional variations in prostate cancer survival, but had little impact for other sites. Unexplained regional variations after adjusting for tumour stage, SES indicators, comorbidity and type of treatment in Norway may be related to regional inequalities in the quality of cancer care. © 2015 UICC.

Impact of Marital Status on Tumor Stage at Diagnosis and on Survival in Male Breast Cancer

OpenAIRE

Adekolujo, Orimisan Samuel; Tadisina, Shourya; Koduru, Ujwala; Gernand, Jill; Smith, Susan Jane; Kakarala, Radhika Ramani

2016-01-01

The effect of marital status (MS) on survival varies according to cancer type and gender. There has been no report on the impact of MS on survival in male breast cancer (MBC). This study aims to determine the influence of MS on tumor stage at diagnosis and survival in MBC. Men with MBC ≥18 years of age in the SEER database from 1990 to 2011 were included in the study. MS was classified as married and unmarried (including single, divorced, separated, widowed). Kaplan–Meier method was used to e...

High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

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Bristow, Robert E; Chang, Jenny; Ziogas, Argyrios; Randall, Leslie M; Anton-Culver, Hoda

2014-02-01

To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers. Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥20 cases/year), high-volume physicians (HVP) (≥10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16-1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22-2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07-2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46-4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90-4.23). Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities. Copyright © 2013

Exo-erythrocytic development of avian malaria and related haemosporidian parasites.

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Valkiūnas, Gediminas; Iezhova, Tatjana A

2017-03-03

Avian malaria parasites (Plasmodium spp.) and related haemosporidians (Haemosporida) are responsible for diseases which can be severe and even lethal in avian hosts. These parasites cause not only blood pathology, but also damage various organs due to extensive exo-erythrocytic development all over the body, which is not the case during Plasmodium infections in mammals. However, exo-erythrocytic development (tissue merogony or schizogony) remains the most poorly investigated part of life cycle in all groups of wildlife haemosporidian parasites. In spite of remarkable progress in studies of genetic diversity, ecology and evolutionary biology of avian haemosporidians during the past 20 years, there is not much progress in understanding patterns of exo-erythrocytic development in these parasites. The purpose of this review is to overview the main information on exo-erythrocytic development of avian Plasmodium species and related haemosporidian parasites as a baseline for assisting academic and veterinary medicine researchers in morphological identification of these parasites using tissue stages, and to define future research priorities in this field of avian malariology. The data were considered from peer-reviewed articles and histological material that was accessed in zoological collections in museums of Australia, Europe and the USA. Articles describing tissue stages of avian haemosporidians were included from 1908 to the present. Histological preparations of various organs infected with the exo-erythrocytic stages of different haemosporidian parasites were examined. In all, 229 published articles were included in this review. Exo-erythrocytic stages of avian Plasmodium, Fallisia, Haemoproteus, Leucocytozoon, and Akiba species were analysed, compared and illustrated. Morphological characters of tissue stages that can be used for diagnostic purposes were specified. Recent molecular studies combined with histological research show that avian haemosporidians are more

Parasite prevalence, infection intensity and richness in an endangered population, the Atlantic-Gaspésie caribou.

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Turgeon, Geneviève; Kutz, Susan J; Lejeune, Manigandan; St-Laurent, Martin-Hugues; Pelletier, Fanie

2018-04-01

The Atlantic-Gaspésie caribou ( Rangifer tarandus caribou ) population is a small isolated relict herd considered endangered according to the Canadian Species at Risk Act (SARA). This population has low recruitment and survival rates but the potential role of parasites on individual fitness is unknown. In this context, we explored the parasite status of this population with the aim of 1) assessing the occurrence and intensity of parasite infections and the spatial, temporal and individual variations, 2) quantifying parasite richness and investigating factors such as sex and host body condition that may be associated with this variable and 3) evaluating the effects of parasite infections on survival in the Atlantic-Gaspésie caribou population. We examined fecal samples from 32 animals captured in 2013-2014 for eggs, oocysts and larvae of parasites and detected 7 parasite species: dorsal-spined larvae protostrongylids, presumably Parelaphostrongylus andersoni based on PCR identification of a subset, Nematodirus odocoilei and other unidentified Strongyles, Trichuris sp., Capillaria sp., Moniezia sp. and Eimeria sp. For each caribou, mean parasite species richness was 1.8 ± 1.1 (SD). Sex, body condition, year and capture location did not explain parasite prevalence, intensity of infection or richness except for intensity of infection of Capillaria sp. that was positively influenced by body condition. Parasites did not influence survival although mortality was higher for males than for females. We suggest that the relatively low and common gastrointestinal and protostrongylid parasite infections will not be a short-term threat leading to extinction.

The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction.

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Hala E Hussein

2017-10-01

Full Text Available Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. Expression of HAP2 has been recognized as critical for the fertilization of parasites in the Babesia-related Plasmodium, and is a leading candidate for a transmission blocking vaccine against malaria. Hereby we identified the B. bovis hap2 gene and demonstrated that it is widely conserved and differentially transcribed during development within the tick midgut, but not by blood stage parasites. The hap2 gene was disrupted by transfecting B. bovis with a plasmid containing the flanking regions of the hap2 gene and the GPF-BSD gene under the control of the ef-1α-B promoter. Comparison of in vitro growth between a hap2-KO B. bovis clonal line and its parental wild type strain showed that HAP2 is not required for the development of B. bovis in erythrocytes. However, xanthurenic acid-in vitro induction experiments of sexual stages of parasites recovered after tick transmission resulted in surface expression of HAP2 exclusively in sexual stage induced parasites. In addition, hap2-KO parasites were not able to develop such sexual stages as defined both by morphology and by expression of the B. bovis sexual marker genes 6-Cys A and B. Together, the data strongly suggests that tick midgut stage differential expression of hap2 is associated with the development of B. bovis sexual forms. Overall these studies are consistent with a role of HAP2 in tick stages of the parasite and suggest that HAP2 is a potential candidate for a transmission blocking vaccine against bovine babesiosis.

Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.

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Alexandra Grote

2017-03-01

Full Text Available Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis.To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode's development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response.This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies.

Adjuvant radiotherapy in stage 1 seminoma: Evaluation of prognostic factors and results of survival

Directory of Open Access Journals (Sweden)

Lasif Serdar

2015-01-01

Conclusion: Adjuvant RT resulted in excellent long-term survival and local control in patients with stage-1 seminoma after orchiectomy. During a short follow-up, secondary malignancy (SM and late cardiovascular morbidity were not observed. Despite those results, concern of SM and late cardiovascular morbidity remains.

Prediction of survival in patients with Stage IV kidney cancer

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L. V. Mirilenko

2015-01-01

Full Text Available The efficiency of treatment was evaluated and the predictors of adjusted survival (AS were identified in patients with disseminated kidney cancer treated at the Republican Research and Practical Center for Oncology and Medical Radiology in 1999 to 2011 (A.E. Okeanov, P.I. Moiseev, L.F. Levin. Malignant tumors in Belarus, 2001–2012. Edited by O.G. Sukonko. Seven factors (regional lymph node metastases; distant bone metastases; a high-grade tumor; sarcomatous tumor differentiation; hemoglobin levels of < 125 g/l in women and < 150 g/l in men; an erythrocyte sedimentation rate of 40 mm/h; palliative surgery were found to have an independent, unfavorable impact on AS. A multidimensional model was built to define what risk group low (no more than 2 poor factors, moderate (3–4 poor factors, and high (more than 4 poor factors the patients with Stage IV kidney cancer belonged to. In these groups, the median survival was 34.7, 17.2, and 4.0 months and 3-year AS rates were 48.6, 24.6, and 3.2 %, respectively. 

Parasite-Mediated Degradation of Synthetic Ozonide Antimalarials Impacts In Vitro Antimalarial Activity.

Science.gov (United States)

Giannangelo, Carlo; Stingelin, Lukas; Yang, Tuo; Tilley, Leann; Charman, Susan A; Creek, Darren J

2018-03-01

The peroxide bond of the artemisinins inspired the development of a class of fully synthetic 1,2,4-trioxolane-based antimalarials, collectively known as the ozonides. Similar to the artemisinins, heme-mediated degradation of the ozonides generates highly reactive radical species that are thought to mediate parasite killing by damaging critical parasite biomolecules. We examined the relationship between parasite dependent degradation and antimalarial activity for two ozonides, OZ277 (arterolane) and OZ439 (artefenomel), using a combination of in vitro drug stability and pulsed-exposure activity assays. Our results showed that drug degradation is parasite stage dependent and positively correlates with parasite load. Increasing trophozoite-stage parasitemia leads to substantially higher rates of degradation for both OZ277 and OZ439, and this is associated with a reduction in in vitro antimalarial activity. Under conditions of very high parasitemia (∼90%), OZ277 and OZ439 were rapidly degraded and completely devoid of activity in trophozoite-stage parasite cultures exposed to a 3-h drug pulse. This study highlights the impact of increasing parasite load on ozonide stability and in vitro antimalarial activity and should be considered when investigating the antimalarial mode of action of the ozonide antimalarials under conditions of high parasitemia. Copyright © 2018 American Society for Microbiology.

A transgenic Plasmodium falciparum NF54 strain that expresses GFP-luciferase throughout the parasite life cycle.

Science.gov (United States)

Vaughan, Ashley M; Mikolajczak, Sebastian A; Camargo, Nelly; Lakshmanan, Viswanathan; Kennedy, Mark; Lindner, Scott E; Miller, Jessica L; Hume, Jen C C; Kappe, Stefan H I

2012-12-01

Plasmodium falciparum is the pathogenic agent of the most lethal of human malarias. Transgenic P. falciparum parasites expressing luciferase have been created to study drug interventions of both asexual and sexual blood stages but luciferase-expressing mosquito stage and liver stage parasites have not been created which has prevented the easy quantification of mosquito stage development (e.g. for transmission blocking interventions) and liver stage development (for interventions that prevent infection). To overcome this obstacle, we have created a transgenic P. falciparum NF54 parasite that expresses a GFP-luciferase transgene throughout the life cycle. Luciferase expression is robust and measurable at all life cycle stages, including midgut oocyst, salivary gland sporozoites and liver stages, where in vivo development is easily measurable using humanized mouse infections in conjunction with an in vivo imaging system. This parasite reporter strain will accelerate testing of interventions against pre-erythrocytic life cycle stages. Copyright © 2012 Elsevier B.V. All rights reserved.

Differential tolerances to ocean acidification by parasites that share the same host.

Science.gov (United States)

MacLeod, C D; Poulin, R

2015-06-01

Ocean acidification is predicted to cause major changes in marine ecosystem structure and function over the next century, as species-specific tolerances to acidified seawater may alter previously stable relationships between coexisting organisms. Such differential tolerances could affect marine host-parasite associations, as either host or parasite may prove more susceptible to the stressors associated with ocean acidification. Despite their important role in many ecological processes, parasites have not been studied in the context of ocean acidification. We tested the effects of low pH seawater on the cercariae and, where possible, the metacercariae of four species of marine trematode parasite. Acidified seawater (pH 7.6 and 7.4, 12.5 °C) caused a 40-60% reduction in cercarial longevity and a 0-78% reduction in metacercarial survival. However, the reduction in longevity and survival varied distinctly between parasite taxa, indicating that the effects of reduced pH may be species-specific. These results suggest that ocean acidification has the potential to reduce the transmission success of many trematode species, decrease parasite abundance and alter the fundamental regulatory role of multi-host parasites in marine ecosystems. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

History of the discovery of the malaria parasites and their vectors

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Cox Francis EG

2010-02-01

Full Text Available Abstract Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium transmitted by female Anopheles species mosquitoes. Our understanding of the malaria parasites begins in 1880 with the discovery of the parasites in the blood of malaria patients by Alphonse Laveran. The sexual stages in the blood were discovered by William MacCallum in birds infected with a related haematozoan, Haemoproteus columbae, in 1897 and the whole of the transmission cycle in culicine mosquitoes and birds infected with Plasmodium relictum was elucidated by Ronald Ross in 1897. In 1898 the Italian malariologists, Giovanni Battista Grassi, Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Camillo Golgi and Ettore Marchiafava demonstrated conclusively that human malaria was also transmitted by mosquitoes, in this case anophelines. The discovery that malaria parasites developed in the liver before entering the blood stream was made by Henry Shortt and Cyril Garnham in 1948 and the final stage in the life cycle, the presence of dormant stages in the liver, was conclusively demonstrated in 1982 by Wojciech Krotoski. This article traces the main events and stresses the importance of comparative studies in that, apart from the initial discovery of parasites in the blood, every subsequent discovery has been based on studies on non-human malaria parasites and related organisms.

Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

International Nuclear Information System (INIS)

Lim, Yu Jin; Kim, Eunji; Kim, Hak Jae; Wu, Hong-Gyun; Yan, Jinchun; Liu, Qin; Patel, Shilpen

2016-01-01

Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Lim, Yu Jin; Kim, Eunji [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Yan, Jinchun [Department of Radiation Oncology, Dalian Medical University, Liaoning (China); Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Liu, Qin [The Wistar Institute, Philadelphia, Pennsylvania (United States); Patel, Shilpen [Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States)

2016-04-01

Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

Overview on the effects of parasites on fish health

Science.gov (United States)

Iwanowicz, D.D.; Cipriano, R.C.; Bruckner, A.W.; Shchelkunov, I.S.

2011-01-01

It is believed by many that parasites are only as important as the fish they infect. Parasites are ubiquitous, primarily surviving in a dynamic equilibrium with their host(s) and they are often overlooked in fish health assessments. Changes in the environment, both anthropogenic and environmental, can alter the parasite/host equilibrium and cause disease or mortality in fish. Therefore it is imperative that we have knowledge of both parasites and parasitic communities within a given population. When fish kills occur, it can often be associated with changes in parasite density and community composition. Often the damage associated with these fish is relative to the rate of infestation with the parasite; a fish that is lightly infected will show few signs of the parasite, while a heavily infected fish may become physiologically impaired and even die. Parasites can cause mechanical damage (fusion of gill lamellae, tissue replacement), physiological damage (cell proliferation, immunomodulation, detrimental behavioral responses, altered growth) and reproductive damage. As parasitism is the most common lifestyle on the planet, understanding its role in the environment may help researchers understand changes in a given fish population or stream ecosystem.

Sequence mining and transcript profiling to explore cyst nematode parasitism

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Recknor Justin

2009-01-01

Full Text Available Abstract Background Cyst nematodes are devastating plant parasites that become sedentary within plant roots and induce the transformation of normal plant cells into elaborate feeding cells with the help of secreted effectors, the parasitism proteins. These proteins are the translation products of parasitism genes and are secreted molecular tools that allow cyst nematodes to infect plants. Results We present here the expression patterns of all previously described parasitism genes of the soybean cyst nematode, Heterodera glycines, in all major life stages except the adult male. These insights were gained by analyzing our gene expression dataset from experiments using the Affymetrix Soybean Genome Array GeneChip, which contains probeset sequences for 6,860 genes derived from preparasitic and parasitic H. glycines life stages. Targeting the identification of additional H. glycines parasitism-associated genes, we isolated 633 genes encoding secretory proteins using algorithms to predict secretory signal peptides. Furthermore, because some of the known H. glycines parasitism proteins have strongest similarity to proteins of plants and microbes, we searched for predicted protein sequences that showed their highest similarities to plant or microbial proteins and identified 156 H. glycines genes, some of which also contained a signal peptide. Analyses of the expression profiles of these genes allowed the formulation of hypotheses about potential roles in parasitism. This is the first study combining sequence analyses of a substantial EST dataset with microarray expression data of all major life stages (except adult males for the identification and characterization of putative parasitism-associated proteins in any parasitic nematode. Conclusion We have established an expression atlas for all known H. glycines parasitism genes. Furthermore, in an effort to identify additional H. glycines genes with putative functions in parasitism, we have reduced the

Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster.

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Paparazzo, Francesco; Tellier, Aurélien; Stephan, Wolfgang; Hutter, Stephan

2015-01-01

The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor.

Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster

Science.gov (United States)

Paparazzo, Francesco; Tellier, Aurélien; Stephan, Wolfgang; Hutter, Stephan

2015-01-01

The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe) and two temperate populations (the Netherlands and North Carolina) with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor. PMID:26154519

Proteomic characterization of larval and adult developmental stages in Echinococcus granulosus reveals novel insight into host-parasite interactions.

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Cui, Shu-Jian; Xu, Lei-Lei; Zhang, Ting; Xu, Ming; Yao, Jun; Fang, Cai-Yun; Feng, Zheng; Yang, Peng-Yuan; Hu, Wei; Liu, Feng

2013-06-12

Cystic hydatid disease is an important zoonosis caused by Echinococcus granulosus infection. The expression profiles of its parasitic life stages and host-Echinococcus interactions remain to be elucidated. Here, we identified 157 adult and 1588 protoscolex proteins (1610 in all), including 1290 novel identifications. Paramyosins and an antigen B (AgB) were the dominant adult proteins. Dog proteins (30) identified in adults indicated diminished local inflammation caused by adult infection. The protoscolex expresses proteins that have been reported to be antigens in other parasites, such as 6-phosphofructokinase and calcineurin B. Pathway analyses suggested that E. granulosus uses both aerobic and anaerobic carbohydrate metabolisms to generate ATP. E. granulosus expresses proteins involved in synthesis and metabolism of lipids or steroids. At least 339 of 390 sheep proteins identified in protoscolex were novel identifications not seen in previous analyses. IgGs and lambda light chains were the most abundant antibody species. Sheep proteins were enriched for detoxification pathways, implying that host detoxification effects play a central role during host-parasite interactions. Our study provides valuable data on E. granulosus expression characteristics, allowing novel insights into the molecular mechanisms involved in host-parasite interactions. In this study, the Echinococcus granulosus adult worm proteome was analyzed for the first time. The protein identification of E. granulosus protoscoleces was extended dramatically. We also identified the most abundant host proteins co-purified with Echinococcus. The results provide useful information pertaining to the molecular mechanisms behind host-Echinococcus interaction and Echinococcus biology. This data also increases the potential for identifying vaccine candidates and new therapeutic targets, and may aid in the development of protein probes for selective and sensitive diagnosis of echinococcosis infection. In

Bacteria isolated from parasitic nematodes - a potential novel vector of pathogens?

OpenAIRE

Lacharme-Lora, Lizeth; Salisbury, Vyv; Humphrey, Tom J.; Stafford, Kathryn; Perkins, Sarah E.

2009-01-01

Bacterial pathogens are ubiquitous in soil and water - concurrently so are free-living helminths that feed on bacteria. These helminths fall into two categories; the non-parasitic and the parasitic. The former have been the focus of previous work, finding that bacterial pathogens inside helminths are conferred survival advantages over and above bacteria alone in the environment, and that accidental ingestion of non-parasitic helminths can cause systemic infection in vertebrate hosts. Here, we...

Effect of Habitat Type on Parasitism of Ectatomma ruidum by Eucharitid Wasps

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Aymer Andrés Vásquez-Ordóñez

2012-01-01

Full Text Available Eucharitidae are parasitoids that use immature stages of ants for their development. Kapala Cameron is the genus most frequently collected in the Neotropics, but little is known about the biology and behavior of any of the species of this genus. We aimed to evaluate the effect of habitat type on eucharitid parasitism and to contribute to the knowledge of the host-parasite relationship between Kapala sp. and the poneromorph ant Ectatomma ruidum (Roger in Colombia. Twenty E. ruidum colonies were extracted from two different habitat types (woodland and grassland, and larvae and cocoons (pupae were examined in search for parasitoids in different stages of development. Globally, 60% of the colonies were parasitized, with 1.3% of larvae and 4% of pupae parasitized. Planidia (first-instar larvae, pupae, and adults of the parasitoid were observed. All of the pupae and adult parasitoids belonged to Kapala iridicolor Cameron. All the colonies collected in the woodlands were parasitized and contained more parasitized larvae (2% and parasitized cocoons (8% than those collected in grasslands (4/12 parasitized colonies, 0.5% parasitized larvae, 0.8% parasitized cocoons. The relationship observed between habitat type and parasitism prevalence is a novel aspect of the study of eucharitid impact on ant host populations.

Parasite prevalence, infection intensity and richness in an endangered population, the Atlantic-Gaspésie caribou

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Geneviève Turgeon

2018-04-01

Full Text Available The Atlantic-Gaspésie caribou (Rangifer tarandus caribou population is a small isolated relict herd considered endangered according to the Canadian Species at Risk Act (SARA. This population has low recruitment and survival rates but the potential role of parasites on individual fitness is unknown. In this context, we explored the parasite status of this population with the aim of 1 assessing the occurrence and intensity of parasite infections and the spatial, temporal and individual variations, 2 quantifying parasite richness and investigating factors such as sex and host body condition that may be associated with this variable and 3 evaluating the effects of parasite infections on survival in the Atlantic-Gaspésie caribou population. We examined fecal samples from 32 animals captured in 2013–2014 for eggs, oocysts and larvae of parasites and detected 7 parasite species: dorsal-spined larvae protostrongylids, presumably Parelaphostrongylus andersoni based on PCR identification of a subset, Nematodirus odocoilei and other unidentified Strongyles, Trichuris sp., Capillaria sp., Moniezia sp. and Eimeria sp. For each caribou, mean parasite species richness was 1.8 ± 1.1 (SD. Sex, body condition, year and capture location did not explain parasite prevalence, intensity of infection or richness except for intensity of infection of Capillaria sp. that was positively influenced by body condition. Parasites did not influence survival although mortality was higher for males than for females. We suggest that the relatively low and common gastrointestinal and protostrongylid parasite infections will not be a short-term threat leading to extinction. Keywords: Capillaria, Eimeria, Moniezia, Nematodirinae, Parelaphostrongylus andersoni, Rangifer tarandus

Mitosis in the Human Malaria Parasite Plasmodium falciparum ▿

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Gerald, Noel; Mahajan, Babita; Kumar, Sanjai

2011-01-01

Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contri...

Limonene Arrests Parasite Development and Inhibits Isoprenylation of Proteins in Plasmodium falciparum

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Moura, Ivan Cruz; Wunderlich, Gerhard; Uhrig, Maria L.; Couto, Alicia S.; Peres, Valnice J.; Katzin, Alejandro M.; Kimura, Emília A.

2001-01-01

Isoprenylation is an essential protein modification in eukaryotic cells. Herein, we report that in Plasmodium falciparum, a number of proteins were labeled upon incubation of intraerythrocytic forms with either [3H]farnesyl pyrophosphate or [3H]geranylgeranyl pyrophosphate. By thin-layer chromatography, we showed that attached isoprenoids are partially modified to dolichol and other, uncharacterized, residues, confirming active isoprenoid metabolism in this parasite. Incubation of blood-stage P. falciparum treated with the isoprenylation inhibitor limonene significantly decreased the parasites' progression from the ring stage to the trophozoite stage and at 1.22 mM, 50% of the parasites died after the first cycle. Using Ras- and Rap-specific monoclonal antibodies, putative Rap and Ras proteins of P. falciparum were immunoprecipitated. Upon treatment with 0.5 mM limonene, isoprenylation of these proteins was significantly decreased, possibly explaining the observed arrest of parasite development. PMID:11502528

Sea lamprey (Petromyzon marinus) parasite-host interactions in the Great Lakes

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Bence, James R.; Bergstedt, Roger A.; Christie, Gavin C.; Cochran, Phillip A.; Ebener, Mark P.; Koonce, Joseph F.; Rutter, Michael A.; Swink, William D.

2003-01-01

Prediction of how host mortality responds to efforts to control sea lampreys (Petromyzon marinus) is central to the integrated management strategy for sea lamprey (IMSL) in the Great Lakes. A parasite-host submodel is used as part of this strategy, and this includes a type-2 multi-species functional response, a developmental response, but no numerical response. General patterns of host species and size selection are consistent with the model assumptions, but some observations appear to diverge. For example, some patterns in sea lamprey marking on hosts suggest increases in selectivity for less preferred hosts and lower host survival when preferred hosts are scarce. Nevertheless, many of the IMSL assumptions may be adequate under conditions targeted by fish community objectives. Of great concern is the possibility that the survival of young parasites (parasitic-phase sea lampreys) varies substantially among lakes or over time. Joint analysis of abundance estimates for parasites being produced in streams and returning spawners could address this. Data on sea lamprey marks is a critical source of information on sea lamprey activity and potential effects. Theory connecting observed marks to sea lamprey feeding activity and host mortality is reviewed. Uncertainties regarding healing and attachment times, the probability of hosts surviving attacks, and problems in consistent classification of marks have led to widely divergent estimates of damages caused by sea lamprey. Laboratory and field studies are recommended to provide a firmer linkage between host blood loss, host mortality, and observed marks on surviving hosts, so as to improve estimates of damage.

Rapid parallel evolution overcomes global honey bee parasite.

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Oddie, Melissa; Büchler, Ralph; Dahle, Bjørn; Kovacic, Marin; Le Conte, Yves; Locke, Barbara; de Miranda, Joachim R; Mondet, Fanny; Neumann, Peter

2018-05-16

In eusocial insect colonies nestmates cooperate to combat parasites, a trait called social immunity. However, social immunity failed for Western honey bees (Apis mellifera) when the ectoparasitic mite Varroa destructor switched hosts from Eastern honey bees (Apis cerana). This mite has since become the most severe threat to A. mellifera world-wide. Despite this, some isolated A. mellifera populations are known to survive infestations by means of natural selection, largely by supressing mite reproduction, but the underlying mechanisms of this are poorly understood. Here, we show that a cost-effective social immunity mechanism has evolved rapidly and independently in four naturally V. destructor-surviving A. mellifera populations. Worker bees of all four 'surviving' populations uncapped/recapped worker brood cells more frequently and targeted mite-infested cells more effectively than workers in local susceptible colonies. Direct experiments confirmed the ability of uncapping/recapping to reduce mite reproductive success without sacrificing nestmates. Our results provide striking evidence that honey bees can overcome exotic parasites with simple qualitative and quantitative adaptive shifts in behaviour. Due to rapid, parallel evolution in four host populations this appears to be a key mechanism explaining survival of mite infested colonies.

Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

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Srivastava, Anubhav; Philip, Nisha; Hughes, Katie R; Georgiou, Konstantina; MacRae, James I; Barrett, Michael P; Creek, Darren J; McConville, Malcolm J; Waters, Andrew P

2016-12-01

Malaria parasites (Plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA) metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

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Anubhav Srivastava

2016-12-01

Full Text Available Malaria parasites (Plasmodium spp. encounter markedly different (nutritional environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

International Nuclear Information System (INIS)

Zhang, Xi-Mei; Li, Ye-Xiong; Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua; Zhou, Li-Qiang; Liu, Xin-Fan; Yu, Zi-Hao

2013-01-01

Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival

Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

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Zhang, Xi-Mei [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Ye-Xiong, E-mail: yexiong@yahoo.com [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Zhou, Li-Qiang [Department of Medical Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Liu, Xin-Fan; Yu, Zi-Hao [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China)

2013-03-15

Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.

Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

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Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

2014-02-01

Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

Fecal Occult Blood Test and Gastrointestinal Parasitic Infection

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Majed H. Wakid

2010-01-01

Full Text Available Stool specimens of 1238 workers in western region of Saudi Arabia were examined for infection with intestinal parasites and for fecal occult blood (FOB to investigate the possibility that enteroparasites correlate to occult intestinal bleeding. Direct smears and formal ether techniques were used for detection of diagnostic stages of intestinal parasites. A commercially available guaiac test was used to detect fecal occult blood. 47.01% of the workers were infected with intestinal parasites including eight helminthes species and eight protozoan species. The results provided no significant evidence (P-value=0.143 that intestinal parasitic infection is in association with positive guaiac FOB test.

Comparison of Survival Rates, Tumor Stages, and Localization in between Obese and Nonobese Patients with Gastric Cancer

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Hakan Kocoglu

2016-01-01

Full Text Available Purpose. In this study we tried to determine the association between body-mass index (BMI, survival rate, and the stage of tumor at the time of diagnosis in patients with gastric cancer. Methods. A total of 270 gastric cancer patients’ hospital records were retrospectively evaluated. Patients were grouped according to their BMI at the time of tumor diagnosis. Tumor stages at admission were compared according to their BMI values. Results. There were no differences in OS among BMI subgroups (p=0.230. The percent of patients with stage III tumor was significantly higher in nonobese while the percent of stage IV tumor was surprisingly higher in obese patients (p was 0.011 and 0.004, resp.. Percent of patients who did not have any surgical intervention was significantly lower in overweight and obese patients than normal and/or underweight patients. Conclusions. At the time of diagnosis, obese patients had significantly higher percent of stage IV tumor than nonobese patients. Despite of that, there were no differences in survival rates among BMI subgroups. Our study results are consistent with “obesity paradox” in gastric cancer patients. We also did not find any relationship between BMI and localization of gastric tumor.

Halophilanema prolata n. gen., n. sp. (Nematoda: Allantonematidae, a parasite of the intertidal bug, Saldula laticollis (Reuter(Hemiptera: Saldidae on the Oregon coast

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Poinar George O

2012-02-01

Full Text Available Abstract Background It is rare to find terrestrial nematode lineages parasitizing arthropods inhabiting the intertidal or littoral zone of the oceans. During an ecological study along the Oregon dunes, an allantonematid nematode (Tylenchomorpha: Allantonematidae was discovered parasitizing the intertidal shore bug, Saldula laticollis (Reuter(Hemiptera: Saldidae. This shore bug is adapted to an intertidal environment and can survive short periods of submergence during high tides. The present study describes the nematode parasite and discusses aspects of its development, ecology and evolution. Methods Adults and last instar nymphs of S. laticollis (Hemiptera: Saldidae were collected from the high intertidal zone among clumps of Juncus L. (Juncaceae plants at Waldport, Oregon on October 3, 2011. The bugs were dissected in 1% saline solution and the nematodes killed in 1% Ringers solution and immediately fixed in 5% formalin (at 20°C. Third stage juveniles removed from infected hosts were maintained in 1% saline solution until they matured to the adult stage, molted and mated. Results Halophilanema prolata n. gen., n. sp. (Nematoda: Allantonematidae is described from last instar nymphs and adults of the intertidal bug, Saldula laticollis on the Oregon coast. The new genus can be distinguished from other genera in the Allantonematidae by a stylet lacking basal knobs in both sexes, an excretory pore located behind the nerve ring, ribbed spicules, a gubernaculum, the absence of a bursa and the elongate-tubular shape of the ovoviviparous parasitic females. Studies of the organogenesis of Halophilanema showed development to third stage juveniles in the uterus of parasitic females. Maturation to the free-living adults and mating occurred in the environment. The incidence of infection of S. laticollis ranged from 0% to 85% depending on the microhabitat in the intertidal zone. Conclusions Based on the habitat and morphological characters, it is proposed

Signalling in malaria parasites – The MALSIG consortium#

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Doerig C.

2009-09-01

Full Text Available Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of Plasmodium, and therefore are, from a public health perspective, strategic targets in the fight against this deadly disease. The MALSIG consortium, which was initiated in February 2009, was designed with the primary objective to integrate research ongoing in Europe and India on i the properties of Plasmodium signalling molecules, and ii developmental processes occurring at various points of the parasite life cycle. On one hand, functional studies of individual genes and their products in Plasmodium falciparum (and in the technically more manageable rodent model Plasmodium berghei are providing information on parasite protein kinases and phosphatases, and of the molecules governing cyclic nucleotide metabolism and calcium signalling. On the other hand, cellular and molecular studies are elucidating key steps of parasite development such as merozoite invasion and egress in blood and liver parasite stages, control of DNA replication in asexual and sexual development, membrane dynamics and trafficking, production of gametocytes in the vertebrate host and further parasite development in the mosquito. This article, which synthetically reviews such signalling molecules and cellular processes, aims to provide a glimpse of the global frame in which the activities of the MALSIG consortium will develop over the next three years.

Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

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Galia Ramírez-Toloza

2017-09-01

Full Text Available American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68, T. cruzi complement regulatory protein (TcCRP, trypomastigote decay-accelerating factor (T-DAF, C2 receptor inhibitor trispanning (CRIT and T. cruzi calreticulin (TcCRT. Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH and plasma membrane-derived vesicles (PMVs. All these proteins inhibit different steps of the classical (CP, alternative (AP or lectin pathways (LP. Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host-parasite

Effect of Interval to Definitive Breast Surgery on Clinical Presentation and Survival in Early-Stage Invasive Breast Cancer

International Nuclear Information System (INIS)

Vujovic, Olga; Yu, Edward; Cherian, Anil; Perera, Francisco; Dar, A. Rashid; Stitt, Larry; Hammond, A.

2009-01-01

Purpose: To examine the effect of clinical presentation and interval to breast surgery on local recurrence and survival in early-stage breast cancer. Methods and Materials: The data from 397 patients with Stage T1-T2N0 breast carcinoma treated with conservative surgery and breast radiotherapy between 1985 and 1992 were reviewed at the London Regional Cancer Program. The clinical presentation consisted of a mammogram finding or a palpable lump. The intervals from clinical presentation to definitive breast surgery used for analysis were 0-4, >4-12, and >12 weeks. The Kaplan-Meier estimates of the time to local recurrence, disease-free survival, and cause-specific survival were determined for the three groups. Cox regression analysis was used to evaluate the effect of clinical presentation and interval to definitive surgery on survival. Results: The median follow-up was 11.2 years. No statistically significant difference was found in local recurrence as a function of the interval to definitive surgery (p = .424). A significant difference was noted in disease-free survival (p = .040) and cause-specific survival (p = .006) with an interval of >12 weeks to definitive breast surgery. However, the interval to definitive surgery was dependent on the presentation for cause-specific survival, with a substantial effect for patients with a mammographic presentation and a negligible effect for patients with a lump presentation (interaction p = .041). Conclusion: The results of this study suggest that an interval of >12 weeks to breast surgery might be associated with decreased survival for patients with a mammographic presentation, but it appeared to have no effect on survival for patients presenting with a palpable breast lump.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

Science.gov (United States)

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Spatial structures in a simple model of population dynamics for parasite-host interactions

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Dong, J. J.; Skinner, B.; Breecher, N.; Schmittmann, B.; Zia, R. K. P.

2015-08-01

Spatial patterning can be crucially important for understanding the behavior of interacting populations. Here we investigate a simple model of parasite and host populations in which parasites are random walkers that must come into contact with a host in order to reproduce. We focus on the spatial arrangement of parasites around a single host, and we derive using analytics and numerical simulations the necessary conditions placed on the parasite fecundity and lifetime for the populations long-term survival. We also show that the parasite population can be pushed to extinction by a large drift velocity, but, counterintuitively, a small drift velocity generally increases the parasite population.

Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

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Horwich, A.; Specht, L.; Ashley, S.

1997-01-01

relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial......To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

Late stage infection in sleeping sickness.

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Hartwig Wolburg

Full Text Available At the turn of the 19(th century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles.

Myrmica Ants and Their Butterfly Parasites with Special Focus on the Acoustic Communication

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F. Barbero

2012-01-01

Full Text Available About 10,000 arthropod species live as ants' social parasites and have evolved a number of mechanisms allowing them to penetrate and survive inside the ant nests. Myrmica colonies, in particular, are exploited by numerous social parasites, and the presence of their overwintering brood, as well as of their polygyny, contributes to make them more vulnerable to infestation. Butterflies of the genus Maculinea are among the most investigated Myrmica inquilines. These lycaenids are known for their very complex biological cycles. Maculinea species are obligated parasites that depend on a particular food plant and on a specific Myrmica species for their survival. Maculinea larvae are adopted by Myrmica ants, which are induced to take them into their nests by chemical mimicry. Then the parasite spends the following 11–23 months inside the ants' nest. Mimicking the acoustic emission of the queen ants, Maculinea parasites not only manage to become integrated, but attain highest rank within the colony. Here we review the biology of Maculinea/Myrmica system with a special focus on some recent breakthrough concerning their acoustical patterns.

Sustainability of a Compartmentalized Host-Parasite Replicator System under Periodic Washout-Mixing Cycles

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Taro Furubayashi

2018-01-01

Full Text Available The emergence and dominance of parasitic replicators are among the major hurdles for the proliferation of primitive replicators. Compartmentalization of replicators is proposed to relieve the parasite dominance; however, it remains unclear under what conditions simple compartmentalization uncoupled with internal reaction secures the long-term survival of a population of primitive replicators against incessant parasite emergence. Here, we investigate the sustainability of a compartmentalized host-parasite replicator (CHPR system undergoing periodic washout-mixing cycles, by constructing a mathematical model and performing extensive simulations. We describe sustainable landscapes of the CHPR system in the parameter space and elucidate the mechanism of phase transitions between sustainable and extinct regions. Our findings revealed that a large population size of compartments, a high mixing intensity, and a modest amount of nutrients are important factors for the robust survival of replicators. We also found two distinctive sustainable phases with different mixing intensities. These results suggest that a population of simple host–parasite replicators assumed before the origin of life can be sustained by a simple compartmentalization with periodic washout-mixing processes.

Tetraoxane-pyrimidine nitrile hybrids as dual stage antimalarials.

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Oliveira, Rudi; Guedes, Rita C; Meireles, Patrícia; Albuquerque, Inês S; Gonçalves, Lídia M; Pires, Elisabete; Bronze, Maria Rosário; Gut, Jiri; Rosenthal, Philip J; Prudêncio, Miguel; Moreira, Rui; O'Neill, Paul M; Lopes, Francisca

2014-06-12

The use of artemisinin or other endoperoxides in combination with other drugs is a strategy to prevent development of resistant strains of Plasmodium parasites. Our previous work demonstrated that hybrid compounds, comprising endoperoxides and vinyl sulfones, were capable of high activity profiles comparable to artemisinin and chloroquine while acting through two distinct mechanisms of action: oxidative stress and falcipain inhibition. In this study, we adapted this approach to a novel class of falcipain inhibitors: peptidomimetic pyrimidine nitriles. Pyrimidine tetraoxane hybrids displayed potent nanomolar activity against three strains of Plasmodium falciparum and falcipain-2, combined with low cytotoxicity. In vivo, a decrease in parasitemia and an increase in survival of mice infected with Plasmodium berghei was observed when compared to control. All tested compounds combined good blood stage activity with significant effects on liver stage parasitemia, a most welcome feature for any new class of antimalarial drug.

Mechanisms of host seeking by parasitic nematodes.

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Gang, Spencer S; Hallem, Elissa A

2016-07-01

The phylum Nematoda comprises a diverse group of roundworms that includes parasites of vertebrates, invertebrates, and plants. Human-parasitic nematodes infect more than one billion people worldwide and cause some of the most common neglected tropical diseases, particularly in low-resource countries [1]. Parasitic nematodes of livestock and crops result in billions of dollars in losses each year [1]. Many nematode infections are treatable with low-cost anthelmintic drugs, but repeated infections are common in endemic areas and drug resistance is a growing concern with increasing therapeutic and agricultural administration [1]. Many parasitic nematodes have an environmental infective larval stage that engages in host seeking, a process whereby the infective larvae use sensory cues to search for hosts. Host seeking is a complex behavior that involves multiple sensory modalities, including olfaction, gustation, thermosensation, and humidity sensation. As the initial step of the parasite-host interaction, host seeking could be a powerful target for preventative intervention. However, host-seeking behavior remains poorly understood. Here we review what is currently known about the host-seeking behaviors of different parasitic nematodes, including insect-parasitic nematodes, mammalian-parasitic nematodes, and plant-parasitic nematodes. We also discuss the neural bases of these behaviors. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterizing Ancylostoma caninum transcriptome and exploring nematode parasitic adaptation

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Hawdon John

2010-05-01

Full Text Available Abstract Background Hookworm infection is one of the most important neglected diseases in developing countries, with approximately 1 billion people infected worldwide. To better understand hookworm biology and nematode parasitism, the present study generated a near complete transcriptome of the canine hookworm Ancylostoma caninum to a very high coverage using high throughput technology, and compared it to those of the free-living nematode Caenorhabditis elegans and the parasite Brugia malayi. Results The generated transcripts from four developmental stages, infective L3, serum stimulated L3, adult male and adult female, covered 93% of the A. caninum transcriptome. The broad diversity among nematode transcriptomes was confirmed, and an impact of parasitic adaptation on transcriptome diversity was inferred. Intra-population analysis showed that A. caninum has higher coding sequence diversity than humans. Examining the developmental expression profiles of A. caninum revealed major transitions in gene expression from larval stages to adult. Adult males expressed the highest number of selectively expressed genes, but adult female expressed the highest number of selective parasitism-related genes. Genes related to parasitism adaptation and A. caninum specific genes exhibited more expression selectivity while those conserved in nematodes tend to be consistently expressed. Parasitism related genes were expressed more selectively in adult male and female worms. The comprehensive analysis of digital expression profiles along with transcriptome comparisons enabled identification of a set of parasitism genes encoding secretory proteins in animal parasitic nematode. Conclusions This study validated the usage of deep sequencing for gene expression profiling. Parasitic adaptation of the canine hookworm is related to its diversity and developmental dynamics. This comprehensive comparative genomic and expression study substantially improves our understanding of

Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial

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Eltabbakh, Gamal H.; Piver, M. Steven; Hempling, Ronald E.; Shin, Kyu H.

1997-01-01

Purpose: The value of adjuvant radiation therapy and staging pelvic lymphadenectomy in patients with low-risk, early-stage endometrial cancer is controversial. The aim of this study was to report the long-term survival, rate of recurrences, and complications in patients with Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion treated with hysterectomy (without formal staging pelvic and periaortic lymph node sampling or lymph-adenectomy) and postoperative vaginal brachytherapy. Methods and Materials: A total of 303 patients with pathologic Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion and nonmalignant peritoneal cytology, were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal brachytherapy (30 Gy to point 0.5 cm depth) in a prospective study extending from 1958 to 1994. In addition, 29 additional Stage I, Grade 1-2 patients with <50% myometrial invasion and malignant peritoneal cytology were treated with 1 year of progesterone therapy. Patients were followed for 1.2-32 years (median 8.1 y). Results: Six patients had recurrences and died secondary to disease. There were no vaginal recurrences. The 5-, 10-, 20-, and 30-year disease-free survivals of the 303 patients with nonmalignant peritoneal cytology were 98.9%, 97.8%, 96.7%, and 96.7%, respectively. Patients with malignant peritoneal cytology had a 5- and 10-year disease-free survival of 100%. Significant radiation complications occurred in 2.1% of the patients. Conclusion: In patients with low-risk, Stage I endometrial cancer, hysterectomy and adjuvant postoperative vaginal brachytherapy provide excellent long-term survival, eliminate vaginal recurrences, and are not associated with significant complications. The addition of 1 year of progesterone therapy to patients with malignant cytology provides 100% long-term survival. Based on these results, patients with low-risk, Stage I endometrial adenocarcinoma do not need

Functional characterization of malaria parasites deficient in the K⁺ channel Kch2

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Ellekvist, Peter; Mlambo, Godfree; Kumar, Nirbhay

2017-01-01

parasite P. berghei, the functional significance of K+ channel homologue PbKch2 was studied using targeted gene knock-out. The knockout parasites were characterized in a mouse model in terms of growth-kinetics and infectivity in the mosquito vector. Furthermore, using a tracer-uptake technique with 86Rb...... of forming oocysts in female Anopheles stephensi mosquitoes. 86Rb+ uptake in Kch2-deficient blood-stage P. berghei parasites (Kch2-null) did not differ from that of wild-type (WT) parasites. About two-thirds of the 86Rb+ uptake in WT and in Kch2-null parasites could be inhibited by K+ channel blockers...... and could be inferred to the presence of functional Kch1 in Kch2 knockout parasites. Kch2 is therefore not required for transport of K+ in P. berghei and is not essential to mosquito-stage sporogonic development of the parasite....

Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster.

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Francesco Paparazzo

Full Text Available The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe and two temperate populations (the Netherlands and North Carolina with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor.

Using cure models for analyzing the influence of pathogens on salmon survival

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Ray, Adam R; Perry, Russell W.; Som, Nicholas A.; Bartholomew, Jerri L

2014-01-01

Parasites and pathogens influence the size and stability of wildlife populations, yet many population models ignore the population-level effects of pathogens. Standard survival analysis methods (e.g., accelerated failure time models) are used to assess how survival rates are influenced by disease. However, they assume that each individual is equally susceptible and will eventually experience the event of interest; this assumption is not typically satisfied with regard to pathogens of wildlife populations. In contrast, mixture cure models, which comprise logistic regression and survival analysis components, allow for different covariates to be entered into each part of the model and provide better predictions of survival when a fraction of the population is expected to survive a disease outbreak. We fitted mixture cure models to the host–pathogen dynamics of Chinook Salmon Oncorhynchus tshawytscha and Coho Salmon O. kisutch and the myxozoan parasite Ceratomyxa shasta. Total parasite concentration, water temperature, and discharge were used as covariates to predict the observed parasite-induced mortality in juvenile salmonids collected as part of a long-term monitoring program in the Klamath River, California. The mixture cure models predicted the observed total mortality well, but some of the variability in observed mortality rates was not captured by the models. Parasite concentration and water temperature were positively associated with total mortality and the mortality rate of both Chinook Salmon and Coho Salmon. Discharge was positively associated with total mortality for both species but only affected the mortality rate for Coho Salmon. The mixture cure models provide insights into how daily survival rates change over time in Chinook Salmon and Coho Salmon after they become infected with C. shasta.

Evaluation of a novel magneto-optical method for the detection of malaria parasites.

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Agnes Orbán

Full Text Available Improving the efficiency of malaria diagnosis is one of the main goals of current malaria research. We have recently developed a magneto-optical (MO method which allows high-sensitivity detection of malaria pigment (hemozoin crystals in blood via the magnetically induced rotational motion of the hemozoin crystals. Here, we evaluate this MO technique for the detection of Plasmodium falciparum in infected erythrocytes using in-vitro parasite cultures covering the entire intraerythrocytic life cycle. Our novel method detected parasite densities as low as ∼ 40 parasites per microliter of blood (0.0008% parasitemia at the ring stage and less than 10 parasites/µL (0.0002% parasitemia in the case of the later stages. These limits of detection, corresponding to approximately 20 pg/µL of hemozoin produced by the parasites, exceed that of rapid diagnostic tests and compete with the threshold achievable by light microscopic observation of blood smears. The MO diagnosis requires no special training of the operator or specific reagents for parasite detection, except for an inexpensive lysis solution to release intracellular hemozoin. The devices can be designed to a portable format for clinical and in-field tests. Besides testing its diagnostic performance, we also applied the MO technique to investigate the change in hemozoin concentration during parasite maturation. Our preliminary data indicate that this method may offer an efficient tool to determine the amount of hemozoin produced by the different parasite stages in synchronized cultures. Hence, it could eventually be used for testing the susceptibility of parasites to antimalarial drugs.

Parasite distribution and early-stage encephalitis in Sarcocystis calchasi infections in domestic pigeons (Columba livia f. domestica).

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Maier, Kristina; Olias, Philipp; Enderlein, Dirk; Klopfleisch, Robert; Mayr, Sylvia L; Gruber, Achim D; Lierz, Michael

2015-01-01

Pigeon protozoal encephalitis is a biphasic, neurologic disease of domestic pigeons (Columba livia f. domestica) caused by the apicomplexan parasite Sarcocystis calchasi. Despite severe inflammatory lesions of the brain, associated parasitic stages have only rarely been identified and the cause of the lesions is still unclear. The aim of this study was therefore to characterize the tissue distribution of S. calchasi within pigeons between the two clinical phases and during the occurrence of neurological signs. For this purpose, a semi-quantitative real-time polymerase chain reaction (PCR) was developed. Forty-five domestic pigeons were infected orally (via a cannula into the crop) with 200 S. calchasi sporocysts and euthanized in groups of three pigeons at intervals of 2 to 10 days over a period of 61 days. Tissue samples including brain and skeletal muscle were examined by histology, immunohistochemistry, and PCR. Schizonts were detected in the liver of one pigeon at day 10 post infection. A mild encephalitis was detected at day 20 post infection, around 4 weeks before the onset of neurological signs. At the same time, immature sarcocysts were present in the skeletal muscle. In seven pigeons a few sarcocysts were identified in the brain, but not associated with any lesion. These results suggest that the encephalitis is induced at a very early stage of the S. calchasi lifecycle rather than in the chronic phase of pigeon protozoal encephalitis. Despite the increasing severity of lesions in the central nervous system, the amount of sarcocysts did not increase. This supports the hypothesis of a delayed-type hypersensitivity response as the cause of the encephalitis. The study also demonstrated that S. calchasi DNA is detectable in tissues negative by histological methods, indicating a higher sensitivity of the real-time PCR.

Influence of Educational Level, Stage, and Histological Type on Survival of Oral Cancer in a Brazilian Population

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Dantas, Thinali Sousa; de Barros Silva, Paulo Goberlânio; Sousa, Eric Fernandes; da Cunha, Maria do PSS; de Aguiar, Andréa Silvia Walter; Costa, Fábio Wildson Gurgel; Mota, Mário Rogério Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu

2016-01-01

Abstract The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juaçaba Hospital – Cancer Institute of Ceará from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia. PMID:26817864

Optimal resource allocation to survival and reproduction in parasitic wasps foraging in fragmented habitats.

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Eric Wajnberg

Full Text Available Expansion and intensification of human land use represents the major cause of habitat fragmentation. Such fragmentation can have dramatic consequences on species richness and trophic interactions within food webs. Although the associated ecological consequences have been studied by several authors, the evolutionary effects on interacting species have received little research attention. Using a genetic algorithm, we quantified how habitat fragmentation and environmental variability affect the optimal reproductive strategies of parasitic wasps foraging for hosts. As observed in real animal species, the model is based on the existence of a negative trade-off between survival and reproduction resulting from competitive allocation of resources to either somatic maintenance or egg production. We also asked to what degree plasticity along this trade-off would be optimal, when plasticity is costly. We found that habitat fragmentation can indeed have strong effects on the reproductive strategies adopted by parasitoids. With increasing habitat fragmentation animals should invest in greater longevity with lower fecundity; yet, especially in unpredictable environments, some level of phenotypic plasticity should be selected for. Other consequences in terms of learning ability of foraging animals were also observed. The evolutionary consequences of these results are discussed.

Parasites and parasite stages of free-ranging wild lions (Panthera leo) of northern Tanzania.

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Bjork, K E; Averbeck, G A; Stromberg, B E

2000-03-01

Fecal samples from 33 lions (Panthera leo) in Serengeti National Park and Ngorongoro Crater Conservation Area in northern Tanzania contained 19 different parasites, 12 of which, including Aelurostrongylus sp., a species of Acanthocephala, a species of Anoplocephalidae, Capillaria sp., Demodex sp., Eimeria sp., Habronema sp., Isospora felis, Isospora rivolta, one species of Isospora that was previously undescribed from lions, one species of Trematoda that was previously undescribed from lions, and Trichuris sp., were new reports for lions. Seven other species had been previously reported from lions.

Evidence-based annotation of the malaria parasite's genome using comparative expression profiling.

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Yingyao Zhou

2008-02-01

Full Text Available A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility, host-cell interactions, sporozoite stage, or rhoptry function. These analyses, together with protein-protein interaction data, provide probabilistic models that predict the function of 926 uncharacterized malaria genes and also suggest that malaria parasites may provide a simple model system for the study of some human processes. These data also provide a foundation for further studies of transcriptional regulation in malaria parasites.

To evaluate disparity between clinical and pathological tumor-node-metastasis staging in oral cavity squamous cell carcinoma patients and its impact on overall survival: An institutional study.

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Gupta, Karan; Panda, Naresh K; Bakshi, Jaimanti; Das, Ashim

2015-01-01

Accurate clinical staging is important for patient counseling, treatment planning, prognostication, and rational design of clinical trials. In head and neck squamous cell carcinoma, discrepancy between clinical and pathological staging has been reported. To evaluate any disparity between clinical and pathological tumor-node-metastasis (TNM) staging in oral cavity squamous cell carcinoma (OCSCC) patients and any impact of the same on survival. Retrospective chart review from year 2007 to 2013, at a tertiary care center. All survival analyses were performed using SPSS for Windows version 15 (Chicago, IL, USA). Disease-free survival curves were generated using Kaplan-Meier algorithm. One hundred and twenty-seven patients with OCSCC were analyzed. Seventy-nine (62.2%) were males and 48 (37.8%) females with a mean age at presentation 43.6 years (29-79 years). The highest congruence between clinical and pathological T-staging seen for clinical stage T1 and T4 at 76.9% and 73.4% with pathological T-stage. Similarly, the highest congruence between clinical and pathological N-stage seen for clinical N0 and N3 at 86.4% and 91.7% with pathological N-stage. Of clinically early stage patients, 67.5% remained early stage, and 32.5% were upstaged to advanced stage following pathological analysis. Of the clinically advanced stage patients, 75% remained advanced, and 25% were pathologically downstaged. This staging discrepancy did not significantly alter the survival. Some disparity exists in clinical and pathological TNM staging of OCSCC, which could affect treatment planning and survival of patients. Hence, more unified and even system of staging for the disease is required for proper decision-making.

The Heme Biosynthesis Pathway Is Essential for Plasmodium falciparum Development in Mosquito Stage but Not in Blood Stages*

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Ke, Hangjun; Sigala, Paul A.; Miura, Kazutoyo; Morrisey, Joanne M.; Mather, Michael W.; Crowley, Jan R.; Henderson, Jeffrey P.; Goldberg, Daniel E.; Long, Carole A.; Vaidya, Akhil B.

2014-01-01

Heme is an essential cofactor for aerobic organisms. Its redox chemistry is central to a variety of biological functions mediated by hemoproteins. In blood stages, malaria parasites consume most of the hemoglobin inside the infected erythrocytes, forming nontoxic hemozoin crystals from large quantities of heme released during digestion. At the same time, the parasites possess a heme de novo biosynthetic pathway. This pathway in the human malaria parasite Plasmodium falciparum has been considered essential and is proposed as a potential drug target. However, we successfully disrupted the first and last genes of the pathway, individually and in combination. These knock-out parasite lines, lacking 5-aminolevulinic acid synthase and/or ferrochelatase (FC), grew normally in blood-stage culture and exhibited no changes in sensitivity to heme-related antimalarial drugs. We developed a sensitive LC-MS/MS assay to monitor stable isotope incorporation into heme from its precursor 5-[13C4]aminolevulinic acid, and this assay confirmed that de novo heme synthesis was ablated in FC knock-out parasites. Disrupting the FC gene also caused no defects in gametocyte generation or maturation but resulted in a greater than 70% reduction in male gamete formation and completely prevented oocyst formation in female Anopheles stephensi mosquitoes. Our data demonstrate that the heme biosynthesis pathway is not essential for asexual blood-stage growth of P. falciparum parasites but is required for mosquito transmission. Drug inhibition of pathway activity is therefore unlikely to provide successful antimalarial therapy. These data also suggest the existence of a parasite mechanism for scavenging host heme to meet metabolic needs. PMID:25352601

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

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Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

2015-01-01

Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

The survival of monogenean (platyhelminth) parasites on fish skin.

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Kearn, G C

1999-01-01

This review deals with the problems faced by those monogenean (platyhelminth) parasites that attach themselves to fish skin. The structure of the skin and the ways in which the posterior hook-bearing haptor achieves virtually permanent attachment to the skin are considered. Small marginal hooklets are specialized for attachment to superficial host epidermal cells, finding anchorage in the terminal web of keratinous tonofilaments, while large hooks (hamuli) may penetrate into and lodge in the collagenous dermis. The complementary roles of suction and sticky secretions in haptor attachment and the role of the pharynx in temporary attachment during feeding are also considered. During leech-like locomotion the haptor is briefly detached and, at this critical time, the anterior end is strongly fixed to the wet, current-swept and possibly slimy skin by a sticky secretion. This secretion is deployed on paired pads or discs, the latter sometimes backed up by suction. After attachment by the haptor is re-established, the special tegument covering the anterior adhesive areas may be instrumental in their instant release. The role of fish skin in the phenomenon of host specificity and in the generation of a defensive response against monogeneans is considered and site-specificity of parasites on the host's body is discussed. Possible selection pressures exerted by predatory 'cleaner' organisms are briefly evaluated.

Advances in the application of genetic manipulation methods to apicomplexan parasites

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Apicomplexan parasites such as Babesia, Theileria, Cryptosporidium, and Toxoplasma have a high negative impact on animal health globally, and improved, cost-effective measures to control them are urgently required. These parasites have complex multi-stage life cycles including obligate intracellular...

Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress.

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Christine R Collins

2013-05-01

Full Text Available The malaria parasite replicates within an intraerythrocytic parasitophorous vacuole (PV. Eventually, in a tightly regulated process called egress, proteins of the PV and intracellular merozoite surface are modified by an essential parasite serine protease called PfSUB1, whilst the enclosing PV and erythrocyte membranes rupture, releasing merozoites to invade fresh erythrocytes. Inhibition of the Plasmodium falciparum cGMP-dependent protein kinase (PfPKG prevents egress, but the underlying mechanism is unknown. Here we show that PfPKG activity is required for PfSUB1 discharge into the PV, as well as for release of distinct merozoite organelles called micronemes. Stimulation of PfPKG by inhibiting parasite phosphodiesterase activity induces premature PfSUB1 discharge and egress of developmentally immature, non-invasive parasites. Our findings identify the signalling pathway that regulates PfSUB1 function and egress, and raise the possibility of targeting PfPKG or parasite phosphodiesterases in therapeutic approaches to dysregulate critical protease-mediated steps in the parasite life cycle.

Lysine Deacetylase Inhibitors in Parasites: Past, Present, and Future Perspectives.

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Hailu, Gebremedhin S; Robaa, Dina; Forgione, Mariantonietta; Sippl, Wolfgang; Rotili, Dante; Mai, Antonello

2017-06-22

Current therapies for human parasite infections rely on a few drugs, most of which have severe side effects, and their helpfulness is being seriously compromised by the drug resistance problem. Globally, this is pushing discovery research of antiparasitic drugs toward new agents endowed with new mechanisms of action. By using a "drug repurposing" strategy, histone deacetylase inhibitors (HDACi), which are presently clinically approved for cancer use, are now under investigation for various parasite infections. Because parasitic Zn 2+ - and NAD + -dependent HDACs play crucial roles in the modulation of parasite gene expression and many of them are pro-survival for several parasites under various conditions, they are now emerging as novel potential antiparasitic targets. This Perspective summarizes the state of knowledge of HDACi (both class I/II HDACi and sirtuin inhibitors) targeted to the main human parasitic diseases (schistosomiasis, malaria, trypanosomiasis, leishmaniasis, and toxoplasmosis) and provides visions into the main issues that challenge their development as antiparasitic agents.

To evaluate disparity between clinical and pathological tumor-node-metastasis staging in oral cavity squamous cell carcinoma patients and its impact on overall survival: An institutional study

Directory of Open Access Journals (Sweden)

Karan Gupta

2015-01-01

Full Text Available Background: Accurate clinical staging is important for patient counseling, treatment planning, prognostication, and rational design of clinical trials. In head and neck squamous cell carcinoma, discrepancy between clinical and pathological staging has been reported. Objective: To evaluate any disparity between clinical and pathological tumor-node-metastasis (TNM staging in oral cavity squamous cell carcinoma (OCSCC patients and any impact of the same on survival. Materials and Methods: Retrospective chart review from year 2007 to 2013, at a tertiary care center. Statistical Analysis: All survival analyses were performed using SPSS for Windows version 15 (Chicago, IL, USA. Disease-free survival curves were generated using Kaplan-Meier algorithm. Results: One hundred and twenty-seven patients with OCSCC were analyzed. Seventy-nine (62.2% were males and 48 (37.8% females with a mean age at presentation 43.6 years (29-79 years. The highest congruence between clinical and pathological T-staging seen for clinical stage T1 and T4 at 76.9% and 73.4% with pathological T-stage. Similarly, the highest congruence between clinical and pathological N-stage seen for clinical N0 and N3 at 86.4% and 91.7% with pathological N-stage. Of clinically early stage patients, 67.5% remained early stage, and 32.5% were upstaged to advanced stage following pathological analysis. Of the clinically advanced stage patients, 75% remained advanced, and 25% were pathologically downstaged. This staging discrepancy did not significantly alter the survival. Conclusion: Some disparity exists in clinical and pathological TNM staging of OCSCC, which could affect treatment planning and survival of patients. Hence, more unified and even system of staging for the disease is required for proper decision-making.

Metabolic Cooperation of Glucose and Glutamine Is Essential for the Lytic Cycle of Obligate Intracellular Parasite Toxoplasma gondii*

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Nitzsche, Richard; Zagoriy, Vyacheslav; Lucius, Richard; Gupta, Nishith

2016-01-01

Toxoplasma gondii is a widespread protozoan parasite infecting nearly all warm-blooded organisms. Asexual reproduction of the parasite within its host cells is achieved by consecutive lytic cycles, which necessitates biogenesis of significant energy and biomass. Here we show that glucose and glutamine are the two major physiologically important nutrients used for the synthesis of macromolecules (ATP, nucleic acid, proteins, and lipids) in T. gondii, and either of them is sufficient to ensure the parasite survival. The parasite can counteract genetic ablation of its glucose transporter by increasing the flux of glutamine-derived carbon through the tricarboxylic acid cycle and by concurrently activating gluconeogenesis, which guarantee a continued biogenesis of ATP and biomass for host-cell invasion and parasite replication, respectively. In accord, a pharmacological inhibition of glutaminolysis or oxidative phosphorylation arrests the lytic cycle of the glycolysis-deficient mutant, which is primarily a consequence of impaired invasion due to depletion of ATP. Unexpectedly, however, intracellular parasites continue to proliferate, albeit slower, notwithstanding a simultaneous deprivation of glucose and glutamine. A growth defect in the glycolysis-impaired mutant is caused by a compromised synthesis of lipids, which cannot be counterbalanced by glutamine but can be restored by acetate. Consistently, supplementation of parasite cultures with exogenous acetate can amend the lytic cycle of the glucose transport mutant. Such plasticity in the parasite's carbon flux enables a growth-and-survival trade-off in assorted nutrient milieus, which may underlie the promiscuous survival of T. gondii tachyzoites in diverse host cells. Our results also indicate a convergence of parasite metabolism with cancer cells. PMID:26518878

Anthropogenic impacts on Costa Rican bat parasitism are sex specific.

Science.gov (United States)

Frank, Hannah K; Mendenhall, Chase D; Judson, Seth D; Daily, Gretchen C; Hadly, Elizabeth A

2016-07-01

While anthropogenic impacts on parasitism of wildlife are receiving growing attention, whether these impacts vary in a sex-specific manner remains little explored. Differences between the sexes in the effect of parasites, linked to anthropogenic activity, could lead to uneven sex ratios and higher population endangerment. We sampled 1108 individual bats in 18 different sites across an agricultural mosaic landscape in southern Costa Rica to investigate the relationships between anthropogenic impacts (deforestation and reductions in host species richness) and bat fly ectoparasitism of 35 species of Neotropical bats. Although female and male bat assemblages were similar across the deforestation gradient, bat fly assemblages tracked their hosts closely only on female bats. We found that in female hosts, parasite abundance per bat decreased with increasing bat species richness, while in male hosts, parasite abundance increased. We hypothesize the differences in the parasite-disturbance relationship are due to differences in roosting behavior between the sexes. We report a sex-specific parasite-disturbance relationship and argue that sex differences in anthropogenic impacts on wildlife parasitism could impact long-term population health and survival.

Survival outcomes in patients with cervical cancer after inclusion of PET/CT in staging procedures

Energy Technology Data Exchange (ETDEWEB)

Hansen, Henrik Villibald [University of Copenhagen, Department of Radiation Oncology, Rigshospitalet, Copenhagen (Denmark); Section for Radiotherapy, Rigshospitalet, Department of Oncology, Copenhagen (Denmark); Loft, Annika [University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Berthelsen, Anne Kiil [University of Copenhagen, Department of Radiation Oncology, Rigshospitalet, Copenhagen (Denmark); University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Christensen, Ib Jarle [University of Copenhagen, The Finsen Laboratory, Rigshospitalet, Copenhagen (Denmark); University of Copenhagen, Biotech Research and Innovation Centre (BRIC), Copenhagen (Denmark); Hoegdall, Claus [University of Copenhagen, Department of Gynecology, Rigshospitalet, Copenhagen (Denmark); Engelholm, Svend Aage [University of Copenhagen, Department of Radiation Oncology, Rigshospitalet, Copenhagen (Denmark)

2015-11-15

In cancer of the uterine cervix, lymph node metastases are associated with a poor prognosis. Even so, the International Federation of Gynecology and Obstetrics (FIGO) does not take into account diagnostic results of methods such as PET/CT, since these are not readily available everywhere. As undetected lymph node metastases can lead to undertreatment, any difference in the underlying prevalence of false-negative scans between CT and PET/CT may be reflected in treatment outcomes. This study investigated survival outcomes in node-negative patients before and after the introduction of PET/CT. This was a single-institution retrospective analysis of 301 patients with a histopathological diagnosis of cervical cancer. The patients were receiving chemoradiotherapy with curative intent according to the standard protocol of the department for patients without lymph node metastases as assessed by pretreatment CT or PET/CT. Patients were stratified into two groups: PET/CT and non-PET/CT. Patient characteristics and treatment outcomes were acquired from the treatment database. Significant differences of 23 % (95 % CI 17 - 29 %), 19 % (95 % CI 13 - 25 %) and 12 % (95 % CI 6 - 18 %) in 5-year overall, disease-free and disease-specific survival, respectively, were observed between the two patient groups. The difference remained significant in univariate and multivariate analyses of overall survival (hazard ratio 0.61, 95 % CI 0.42 - 0.89; p = 0.010), including age, FIGO stage, performance status, BMI, and histopathology. Inclusion of PET/CT in the preradiotherapy diagnostic protocol may lead to nodal stage migration not reflected in the FIGO stage. It was found to be a significant covariate, and could lead to selection bias that needs to be taken into account when designing and reporting on clinical trials. (orig.)

Survival outcomes in patients with cervical cancer after inclusion of PET/CT in staging procedures

International Nuclear Information System (INIS)

Hansen, Henrik Villibald; Loft, Annika; Berthelsen, Anne Kiil; Christensen, Ib Jarle; Hoegdall, Claus; Engelholm, Svend Aage

2015-01-01

In cancer of the uterine cervix, lymph node metastases are associated with a poor prognosis. Even so, the International Federation of Gynecology and Obstetrics (FIGO) does not take into account diagnostic results of methods such as PET/CT, since these are not readily available everywhere. As undetected lymph node metastases can lead to undertreatment, any difference in the underlying prevalence of false-negative scans between CT and PET/CT may be reflected in treatment outcomes. This study investigated survival outcomes in node-negative patients before and after the introduction of PET/CT. This was a single-institution retrospective analysis of 301 patients with a histopathological diagnosis of cervical cancer. The patients were receiving chemoradiotherapy with curative intent according to the standard protocol of the department for patients without lymph node metastases as assessed by pretreatment CT or PET/CT. Patients were stratified into two groups: PET/CT and non-PET/CT. Patient characteristics and treatment outcomes were acquired from the treatment database. Significant differences of 23 % (95 % CI 17 - 29 %), 19 % (95 % CI 13 - 25 %) and 12 % (95 % CI 6 - 18 %) in 5-year overall, disease-free and disease-specific survival, respectively, were observed between the two patient groups. The difference remained significant in univariate and multivariate analyses of overall survival (hazard ratio 0.61, 95 % CI 0.42 - 0.89; p = 0.010), including age, FIGO stage, performance status, BMI, and histopathology. Inclusion of PET/CT in the preradiotherapy diagnostic protocol may lead to nodal stage migration not reflected in the FIGO stage. It was found to be a significant covariate, and could lead to selection bias that needs to be taken into account when designing and reporting on clinical trials. (orig.)

Two-stage meta-analysis of survival data from individual participants using percentile ratios

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Barrett, Jessica K; Farewell, Vern T; Siannis, Fotios; Tierney, Jayne; Higgins, Julian P T

2012-01-01

Methods for individual participant data meta-analysis of survival outcomes commonly focus on the hazard ratio as a measure of treatment effect. Recently, Siannis et al. (2010, Statistics in Medicine 29:3030–3045) proposed the use of percentile ratios as an alternative to hazard ratios. We describe a novel two-stage method for the meta-analysis of percentile ratios that avoids distributional assumptions at the study level. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22825835

Sex steroids, immune system, and parasitic infections: facts and hypotheses.

Science.gov (United States)

Nava-Castro, Karen; Hernández-Bello, Romel; Muñiz-Hernández, Saé; Camacho-Arroyo, Ignacio; Morales-Montor, Jorge

2012-07-01

It has been widely reported that the incidence and the severity of natural parasitic infections are different between males and females of several species, including humans. This sexual dimorphism involves a distinct exposure of males and females to various parasite infective stages, differential effects of sex steroids on immune cells, and direct effects of these steroids on parasites, among others. Typically, for a large number of parasitic diseases, the prevalence and intensity is higher in males than females; however, in several parasitic infections, males are more resistant than females. In the present work, we review the effects of sex hormones on immunity to protozoa and helminth parasites, which are the causal agents of several diseases in humans, and discuss the most recent research related to the role of sex steroids in the complex host-parasite relationship. © 2012 New York Academy of Sciences.

Plasmodial Hsp70s are functionally adapted to the malaria parasite life cycle

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Jude M Przyborski

2015-06-01

Full Text Available The human malaria parasite, Plasmodium falciparum, encodes a minimal complement of six heat shock protein 70s (PfHSP70s, some of which are highly expressed and are thought to play an important role in the survival and pathology of the parasite. In addition to canonical features of molecular chaperones, these HSP70s possess properties that reflect functional adaptation to a parasitic life style, including resistance to thermal insult during fever periods and host-parasite interactions. The parasite even exports an HSP70 to the host cell where it is likely to be involved in host cell modification. This review focuses on the features of the PfHSP70s, particularly with respect to their adaptation to the malaria parasite life cycle.

Effects of waterborne zinc on reproduction, survival and morphometrics of Gyrodactylus turnbulli (Monogenea) on guppies (Poecilia reticulata).

Science.gov (United States)

Gheorghiu, Cristina; Cable, Joanne; Marcogliese, David J; Scott, Marilyn E

2007-03-01

Recent reviews indicate that pollutants in the surrounding macroenvironment directly influence the population dynamics, distribution and dispersal of fish ectoparasites, often leading to increased parasitism. The aim of the current study was to explore the effects of sublethal concentrations of waterborne zinc (up to 240 microg Zn/L) on survival, reproduction and morphometrics of Gyrodactylus turnbulli, a viviparous monogenean infecting the skin and fins of the guppy, Poecilia reticulata. Parasite survival and reproduction on the fish were recorded daily for individual parasites maintained in isolated containers. Both survival and reproduction were reduced in 30 and 120 microg Zn/L, compared with 0, 15, and 60 microg Zn/L indicating direct toxic effects of Zn on the parasite. However, as generation time was unaffected by Zn, we attribute the reduced reproduction to the shorter lifespan. Parasite survival off the fish was monitored hourly. Average lifespan of the detached parasites decreased linearly from 19.5 h in 0 microg Zn/L to 17.3h in 240 microg Zn/L, further supporting the direct toxic effect of Zn to the parasite. In addition, temporal dynamics of parasite morphometrics were monitored from mini-epidemics sampled after 1, 5, 10, and 15 days exposure to various Zn concentrations. All morphological parameters decreased significantly in response both to concentration and duration of exposure to waterborne Zn. Together these data clearly indicate that concentrations as low as 120 microg Zn/L are directly toxic to G. turnbulli.

Molecular Genetic Analysis of Parasite Survival in P. falciparum Malaria.

Science.gov (United States)

1991-03-15

conducting research utilizing recombinant DNA technology , the investigator(s) adhered to current guidelines promulgated by the National Institute of Health...oligonucleotides unrelated to the conserved elements of Plasmodium falciparum were used (lane marked random oligo). Furthermore, extracts prepared...once with Ix Trager’s buffer. The following steps were carried out on ice. Erythrocytes were lysed in 0.05% saponin (19). The released parasites were

Motility, Force Generation, and Energy Consumption of Unicellular Parasites.

Science.gov (United States)

Hochstetter, Axel; Pfohl, Thomas

2016-07-01

Motility is a key factor for pathogenicity of unicellular parasites, enabling them to infiltrate and evade host cells, and perform several of their life-cycle events. State-of-the-art methods of motility analysis rely on a combination of optical tweezers with high-resolution microscopy and microfluidics. With this technology, propulsion forces, energies, and power generation can be determined so as to shed light on the motion mechanisms, chemotactic behavior, and specific survival strategies of unicellular parasites. With these new tools in hand, we can elucidate the mechanisms of motility and force generation of unicellular parasites, and identify ways to manipulate and eventually inhibit them. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disentangling phylogenetic constraints from selective forces in the evolution of trematode transmission stages

NARCIS (Netherlands)

Koehler, A.V.; Brown, B.; Poulin, R.; Thieltges, D.W.; Fredensborg, B.L.

2012-01-01

The transmission stages of parasites are key determinants of parasite fitness, but they also incur huge mortality. Yet the selective forces shaping the sizes of transmission stages remain poorly understood. We ran a comparative analysis of interspecific variation in the size of transmission stages

Early-Stage Classic Hodgkin Lymphoma: The Utilization of Radiation Therapy and Its Impact on Overall Survival

Energy Technology Data Exchange (ETDEWEB)

Parikh, Rahul R., E-mail: rparikh@chpnet.org [Department of Radiation Oncology, Mount Sinai Beth Israel Medical Center and Mount Sinai St. Luke' s-Roosevelt Hospitals, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, New York (United States); Grossbard, Michael L. [Division of Hematology-Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York (United States); Harrison, Louis B. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Yahalom, Joachim [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2015-11-01

Purpose: To examine the association between radiation therapy (RT) utilization and overall survival (OS) for patients with early-stage Hodgkin lymphoma (HL). Methods and Materials: Using the National Cancer Database, we evaluated clinical features and survival outcomes among patients diagnosed with stage I/II HL from 1998 to 2011. The association between RT use, covariables, and outcome was assessed in a Cox proportional hazards regression model. Propensity score matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. Results: Among the 41,943 patients in the National Cancer Database with stage I/II HL, 29,752 patients were analyzed for this study. Radiation therapy use was associated with younger age (≤40 years), favorable insured status, higher socioeconomic status (income, education), and treatment at comprehensive community cancer centers (all P<.05). Five-year OS for patients receiving RT was 94.5%, versus 88.9% for those not receiving RT (P<.01). Radiation therapy use was a significant predictor of OS in the “As-Treated” cohort (hazard ratio 0.53, 95% confidence interval 0.49-0.58, P<.01) and intention-to-treat analysis (P<.01). After propensity score matching based on clinicopathologic characteristics, RT use remained associated with improved OS (hazard ratio 0.46, 95% confidence interval 0.38-0.56, P<.01). Over the study period, RT utilization for this cohort decreased from 55% to 44%, most commonly because it was not part of the planned initial treatment strategy. Conclusions: Consolidation RT was associated with improved OS for patients with early-stage classic HL. We also have identified patient-specific variations in the use of RT that may be targeted to improve patient access to care.

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

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McMahon-Pratt, Diane; Saravia, Nancy Gore

2015-01-01

Background Therapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses. Methodology To achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays. Principal Findings Anti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine

The genome and life-stage specific transcriptomes of Globodera pallida elucidate key aspects of plant parasitism by a cyst nematode.

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Cotton, James A; Lilley, Catherine J; Jones, Laura M; Kikuchi, Taisei; Reid, Adam J; Thorpe, Peter; Tsai, Isheng J; Beasley, Helen; Blok, Vivian; Cock, Peter J A; Eves-van den Akker, Sebastian; Holroyd, Nancy; Hunt, Martin; Mantelin, Sophie; Naghra, Hardeep; Pain, Arnab; Palomares-Rius, Juan E; Zarowiecki, Magdalena; Berriman, Matthew; Jones, John T; Urwin, Peter E

2014-03-03

Globodera pallida is a devastating pathogen of potato crops, making it one of the most economically important plant parasitic nematodes. It is also an important model for the biology of cyst nematodes. Cyst nematodes and root-knot nematodes are the two most important plant parasitic nematode groups and together represent a global threat to food security. We present the complete genome sequence of G. pallida, together with transcriptomic data from most of the nematode life cycle, particularly focusing on the life cycle stages involved in root invasion and establishment of the biotrophic feeding site. Despite the relatively close phylogenetic relationship with root-knot nematodes, we describe a very different gene family content between the two groups and in particular extensive differences in the repertoire of effectors, including an enormous expansion of the SPRY domain protein family in G. pallida, which includes the SPRYSEC family of effectors. This highlights the distinct biology of cyst nematodes compared to the root-knot nematodes that were, until now, the only sedentary plant parasitic nematodes for which genome information was available. We also present in-depth descriptions of the repertoires of other genes likely to be important in understanding the unique biology of cyst nematodes and of potential drug targets and other targets for their control. The data and analyses we present will be central in exploiting post-genomic approaches in the development of much-needed novel strategies for the control of G. pallida and related pathogens.

Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Chang Joe Y

2012-09-01

Full Text Available Abstract Background Stereotactic ablative radiotherapy (SABR can achieve excellent local control rates in early-stage non-small cell lung cancer (NSCLC and has emerged as a standard treatment option for patients who cannot undergo surgery or those with isolated recurrences. However, factors that may predict toxicity or survival are largely unknown. We sought here to identify predictors of survival and pneumonitis after SABR for NSCLC in a relatively large single-institution series. Methods Subjects were 130 patients with stage I NSCLC treated with four-dimensional computed tomography (4D CT –planned, on-board volumetric image–guided SABR to 50 Gy in 4 fractions. Disease was staged by positron emission tomography/computed tomography (PET/CT and scans were obtained again at the second follow-up after SABR. Results At a median follow-up time of 26 months, the 2-year local control rate was 98.5%. The median overall survival (OS time was 60 months, and OS rates were 93.0% at 1 year, 78.2% at 2 years, and 65.3% at 3 years. No patient experienced grade 4–5 toxicity; 15 had radiation pneumonitis (12 [9.3%] grade 2 and 3 [2.3%] grade 3. Performance status, standardized uptake value (SUVmax on staging PET/CT, tumor histology, and disease operability were associated with OS on univariate analysis, but only staging SUVmax was independently predictive on multivariate analysis (P = 0.034. Dosimetric factors were associated with radiation pneumonitis on univariate analysis, but only mean ipsilateral lung dose ≥9.14 Gy was significant on multivariate analysis (P = 0.005. Conclusions OS and radiation pneumonitis after SABR for stage I NSCLC can be predicted by staging PET SUVmax and ipsilateral mean lung dose, respectively.

Metabolic Cooperation of Glucose and Glutamine Is Essential for the Lytic Cycle of Obligate Intracellular Parasite Toxoplasma gondii.

Science.gov (United States)

Nitzsche, Richard; Zagoriy, Vyacheslav; Lucius, Richard; Gupta, Nishith

2016-01-01

Toxoplasma gondii is a widespread protozoan parasite infecting nearly all warm-blooded organisms. Asexual reproduction of the parasite within its host cells is achieved by consecutive lytic cycles, which necessitates biogenesis of significant energy and biomass. Here we show that glucose and glutamine are the two major physiologically important nutrients used for the synthesis of macromolecules (ATP, nucleic acid, proteins, and lipids) in T. gondii, and either of them is sufficient to ensure the parasite survival. The parasite can counteract genetic ablation of its glucose transporter by increasing the flux of glutamine-derived carbon through the tricarboxylic acid cycle and by concurrently activating gluconeogenesis, which guarantee a continued biogenesis of ATP and biomass for host-cell invasion and parasite replication, respectively. In accord, a pharmacological inhibition of glutaminolysis or oxidative phosphorylation arrests the lytic cycle of the glycolysis-deficient mutant, which is primarily a consequence of impaired invasion due to depletion of ATP. Unexpectedly, however, intracellular parasites continue to proliferate, albeit slower, notwithstanding a simultaneous deprivation of glucose and glutamine. A growth defect in the glycolysis-impaired mutant is caused by a compromised synthesis of lipids, which cannot be counterbalanced by glutamine but can be restored by acetate. Consistently, supplementation of parasite cultures with exogenous acetate can amend the lytic cycle of the glucose transport mutant. Such plasticity in the parasite's carbon flux enables a growth-and-survival trade-off in assorted nutrient milieus, which may underlie the promiscuous survival of T. gondii tachyzoites in diverse host cells. Our results also indicate a convergence of parasite metabolism with cancer cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

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Chim Chor

2010-11-01

Full Text Available Abstract Background Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM. We have reported a promising complete remission (CR rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. Methods Herein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS and overall survival (OS. Results With a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS. Conclusions Our staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.

Transformation of the rodent malaria parasite Plasmodium chabaudi

OpenAIRE

Spence, Philip J; Cunningham, Deirdre; Jarra, William; Lawton, Jennifer; Langhorne, Jean; Thompson, Joanne

2011-01-01

The rodent malaria parasite Plasmodium chabaudi chabaudi shares many features with human malaria species, including P. falciparum, and is the in vivo model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. this protocol describes an optimized method for the transformation of mature blood-stage P.c. chabaudi and a description of a vector that targets efficient, sing...

Metazoan-protozoan parasite co-infections and host body weight in St Kilda Soay sheep.

Science.gov (United States)

Craig, B H; Tempest, L J; Pilkington, J G; Pemberton, J M

2008-04-01

For hundreds of years, the unmanaged Soay sheep population on St Kilda has survived despite enduring presumably deleterious co-infections of helminth, protozoan and arthropod parasites and intermittent periods of starvation. Important parasite taxa in young Soay sheep are strongyles (Trichostrongylus axei, Trichostrongylus vitrinus and Teladorsagia circumcincta), coccidia (11 Eimeria species) and keds (Melophagus ovinus) and in older animals, Teladorsagia circumcincta. In this research, associations between the intensity of different parasite taxa were investigated. Secondly, the intensities of different parasite taxa were tested for associations with variation in host weight, which is itself a determinant of over-winter survival in the host population. In lambs, the intensity of strongyle eggs was positively correlated with that of Nematodirus spp. eggs, while in yearlings and adults strongyle eggs and coccidia oocysts were positively correlated. In lambs and yearlings, of the parasite taxa tested, only strongyle eggs were significantly and negatively associated with host weight. However, in adult hosts, strongyles and coccidia were independently and negatively associated with host weight. These results are consistent with the idea that strongyles and coccidia are exerting independent selection on Soay sheep.

Computed tomography in the evaluation of malignant pleural mesothelioma-Association of tumor size to a sarcomatoid histology, a more advanced TNM stage and poor survival.

Science.gov (United States)

Paajanen, Juuso; Laaksonen, Sanna; Ilonen, Ilkka; Wolff, Henrik; Husgafvel-Pursiainen, Kirsti; Kuosma, Eeva; Ollila, Hely; Myllärniemi, Marjukka; Vehmas, Tapio

2018-02-01

Appropriate clinical staging of malignant pleural mesothelioma (MPM) is critical for correct treatment decisions. Newly revised TNM staging protocol has been released for MPM. We investigated baseline computed tomography (CT) characteristics of MPM patients, the new staging system and a simple tumor size (TS) assessment in terms of survival. As part of our study that included all MPM patients diagnosed in Finland 2000-2012, we retrospectively reviewed 161 CT scans of MPM patients diagnosed between 2007 and 2012 in the Hospital District of Helsinki and Uusimaa. TS was estimated by using the maximal tumor thickness and grading tumor extension along the chest wall. Cox Regression models were used to identify relationships between survival, clinicopathological factors and CT-findings. The median length of follow-up was 9.7 months and the median survival 9.1 months. The right sided tumors tended to be more advanced at baseline and had worse prognosis in the univariate analyses. In the multivariate survival model, TS, pleural effusion along with non-epithelioid histology were predictors of poor survival. Tumor size correlated significantly with a sarcomatoid histopathological finding and several parameters linked to a more advanced TNM stage. Most patients were diagnosed with locally advanced stage, while 12 (7%) had no sign of the tumor in CT. In this study, we demonstrate a novel approach for MPM tumor size evaluation that has a strong relationship with mortality, sarcomatoid histology and TNM stage groups. TS could be used for prognostic purposes and it may be a useful method for assessing therapy responses. Copyright © 2018 Elsevier B.V. All rights reserved.

Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity

Energy Technology Data Exchange (ETDEWEB)

Zuliani, Antonio Carlos; Cunha, Maercio de Oliveira, E-mail: aczo.rt@gmail.co [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Esteves, Sergio C.B. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Secao de Radioterapia; Teixeira, Julio Cesar [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Tocoginecologia

2010-07-01

Objective: to compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR), high-dose-rate (HDR) brachytherapy and association of HDR and chemotherapy. Methods: between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m2. Results: the five-year progression-free survival (PFS) was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02). The five-year Overall Survival (OS) was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p 0.02). Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. Conclusion: patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups. (author)

Transgastric pure-NOTES peritoneoscopy and endoscopic ultrasonography for staging of gastrointestinal cancers: a survival and feasibility study.

Science.gov (United States)

Donatsky, Anders Meller; Vilmann, Peter; Meisner, Søren; Jørgensen, Lars Nannestad; Rosenberg, Jacob

2012-06-01

Human natural orifice transluminal endoscopic surgery (NOTES) has mainly been based on simultaneous laparoscopic assistance (hybrid NOTES), forgoing the theoretical benefits of the NOTES technique. This is due to a lack of NOTES-specific instruments and endoscopes, making pure-NOTES procedures difficult and time consuming. An area where pure NOTES could be adopted at its present stage of development is minimally invasive staging of gastrointestinal (GI) cancer. The aim of this study is to evaluate the feasibility of combining transgastric (TG) pure-NOTES peritoneoscopy and intraperitoneal endoscopic ultrasonography (ip-EUS) with intraluminal EUS (il-EUS) for peritoneal evaluation. This was a feasibility and survival study where il-EUS followed by ip-EUS and peritoneoscopy was performed in 10 pigs subjected to TG pure NOTES. A score was given with regard to achieved visualisation of predefined anatomical structures. Survival was assessed at postoperative day (POD) 14. All animals survived until POD 14. Median total procedural time was 94 min (range 74-130 min). Median time for il-EUS, ip-EUS and peritoneoscopy was 11 min (range 7-14 min), 13 min (range 8-20 min) and 10 min (range 6-23 min). Il-EUS, ip-EUS and peritoneoscopy resulted in a score of 15/15 points (range 14-15 points), 6/9 points (range 1-8 points) and 12/13 points (range 8-13 points). TG pure-NOTES peritoneoscopy and ip-EUS combined with il-EUS is feasible and provides sufficient peritoneal evaluation. The technique could have potential for minimally invasive staging of GI cancers.

Plasmodium berghei Δp52&p36 parasites develop independent of a parasitophorous vacuole membrane in Huh-7 liver cells.

Science.gov (United States)

Ploemen, Ivo H J; Croes, Huib J; van Gemert, Geert-Jan J; Wijers-Rouw, Mietske; Hermsen, Cornelus C; Sauerwein, Robert W

2012-01-01

The proteins P52 and P36 are expressed in the sporozoite stage of the murine malaria parasite Plasmodium berghei. Δp52&p36 sporozoites lacking expression of both proteins are severely compromised in their capability to develop into liver stage parasites and abort development soon after invasion; presumably due to the absence of a parasitophorous vacuole membrane (PVM). However, a small proportion of P. berghei Δp52&p36 parasites is capable to fully mature in hepatocytes causing breakthrough blood stage infections. We have studied the maturation of replicating Δp52&p36 parasites in cultured Huh-7 hepatocytes. Approximately 50% of Δp52&p36 parasites developed inside the nucleus of the hepatocyte but did not complete maturation and failed to produce merosomes. In contrast cytosolic Δp52&p36 parasites were able to fully mature and produced infectious merozoites. These Δp52&p36 parasites developed into mature schizonts in the absence of an apparent parasitophorous vacuole membrane as shown by immunofluorescence and electron microscopy. Merozoites derived from these maturing Δp52&p36 liver stages were infectious for C57BL/6 mice.

Mortality selection during the 2003 European heat wave in three-spined sticklebacks: effects of parasites and MHC genotype

Directory of Open Access Journals (Sweden)

Milinski Manfred

2008-04-01

Full Text Available Abstract Background Ecological interaction strength may increase under environmental stress including temperature. How such stress enhances and interacts with parasite selection is almost unknown. We studied the importance of resistance genes of the major histocompatibility complex (MHC class II in 14 families of three-spined sticklebacks Gasterosteus aculeatus exposed to their natural macroparasites in field enclosures in the extreme summer of 2003. Results After a mass die-off during the 2003-European heat wave killing 78% of 277 experimental fish, we found strong differences in survival among and within families. In families with higher average parasite load fewer individuals survived. Multivariate analysis revealed that the composition of the infecting parasite fauna was family specific. Within families, individuals with an intermediate number of MHC class IIB sequence variants survived best and had the lowest parasite load among survivors, suggesting a direct functional link between MHC diversity and fitness. The within family MHC effects were, however, small compared to between family effects, suggesting that other genetic components or non-genetic effects were also important. Conclusion The correlation between parasite load and mortality that we found at both individual and family level might have appeared only in the extraordinary heatwave of 2003. Due to global warming the frequency of extreme climatic events is predicted to increase, which might intensify costs of parasitism and enhance selection on immune genes.

Combination of transcatheter arterial chemoembolization and interrupted dosing sorafenib improves patient survival in early–intermediate stage hepatocellular carcinoma

Science.gov (United States)

Lee, Teng-Yu; Lin, Chen-Chun; Chen, Chiung-Yu; Wang, Tsang-En; Lo, Gin-Ho; Chang, Chi-Sen; Chao, Yee

2017-01-01

Abstract Background/Objective: The survival benefit of treatment for unresectable hepatocellular carcinoma (HCC) with transcatheter arterial chemoembolization (TACE) combined with sorafenib remains uncertain. We compared the survival of patients treated with TACE and sorafenib with that of patients treated with TACE alone. Methods: This was a post hoc analysis of the Study in Asia of the Combination of TACE with Sorafenib in Patients with HCC (START) trial. All patients who received TACE and interrupted dosing of sorafenib for early or intermediate-stage HCC in Taiwan from 2009 to 2010 were recruited into the TACE and sorafenib group. They were randomly matched 1:1 by age, sex, Child–Pugh score, tumor size, tumor number, and tumor stage with patients from Taichung Veterans General Hospital in Taiwan who received TACE alone and who fulfilled the selection criteria of the START trial during the same time period (control group). Patient survival [cumulative incidence and hazard ratio (HR)] of the 2 groups were analyzed and compared. Results: The baseline characteristics of the 36 patients in each group were similar. Tumor response rates were significantly better in the TACE and sorafenib group (P < .04). Overall survival of the TACE and sorafenib group was also significantly better than that of the control (TACE alone) group over the 2 years [78%, 95% confidence interval (95% CI) 64–91 vs 49, 95% CI 32–66; P = .012]. In the multivariate regression analysis, TACE and sorafenib was found to be independently associated with a decreased risk of mortality (HR 0.33, 95% CI 0.12–0.89; P = .015). Multivariate stratified analyses verified this association in each patient subgroup (all HR < 1.0). Conclusion: With a high patient tolerance to an interrupted sorafenib dosing schedule, the combination of TACE with sorafenib was associated with improved overall survival in early–intermediate stage HCC when compared with treatment with TACE alone. PMID

Invaders interfere with native parasite-host interactions

DEFF Research Database (Denmark)

Thieltges, David W.; Reise, Karsten; Prinz, Katrin

2009-01-01

The introduction of species is of increasing concern as invaders often reduce the abundance of native species due to a variety of interactions like habitat engineering, predation and competition. A more subtle and not recognized effect of invaders on their recipient biota is their potential...... interference with native parasite-host interactions. Here, we experimentally demonstrate that two invasive molluscan filter-feeders of European coastal waters interfere with the transmission of free-living infective trematode larval stages and hereby mitigate the parasite burden of native mussels (Mytilus...

5-YEAR SURVIVAL OF PATIENTS WITH STAGE II UTERINE CANCER DEPENDING ON MORPHOLOGIC FEATURES OF TUMOR

Directory of Open Access Journals (Sweden)

Ye. A. Mustafina

2008-01-01

Full Text Available Retrospective data of treatment results of 109 patients with rarely observed stage II uterine cancer, admitted to N.N. Blokhin Russian Cancer Research Center from 1980 to 2000 is analyzed. Correlation of overall 5-year survival rates of stage IIA and IIB uterine can- cer patients with a number of tumor morphologic features is studied. The influence of some non-elucidated morphologic features of stage IIA and IIB uterine cancer such as the degree of cellular anaplasia, the depth of tumor invasion into the uterine neck, lymho- vascular invasion into the myometrium and uterine neck, microscopic vessels density in the area of the most extensive invasion, the presence of necrotic areas in the tumor tissue on long-term treatment results are analyzed.

Microarray analysis of gender- and parasite-specific gene transcription in Strongyloides ratti

NARCIS (Netherlands)

Evans, Helen; Mello, Luciane V.; Fang, Yongxiang; Wit, Ernst; Thompson, Fiona J.; Viney, Mark E.; Paterson, Steve

2008-01-01

The molecular mechanisms by which parasitic nematodes reproduce and have adapted to life within a host are unclear. In the present study, microarray analysis was used to explore differential transcription among the different stages and sexes of Strongyloides ratti, a parasitic nematode of brown

Species and cultivar influences on survival and parasitism of fall armyworm.

Science.gov (United States)

Braman, S K; Duncan, R R; Hanna, W W; Engelke, M C

2004-12-01

Interactions between host plant resistance and biological control may benefit or hinder pest management efforts. Turfgrass cultivars have rarely been tested for extrinsic resistance characteristics such as occurrence and performance of beneficial arthropods on plant genotypes with resistance to known turf pests. Parasitism of fall armyworm, Spodoptera frugiperda (J.E. Smith), among six turfgrass genotypes was evaluated. The six grasses tested [Sea Isle-1 and 561-79 seashore paspalum, Paspalum vaginatum Swartz; TifSport and TifEagle hybrid Bermuda grass, Cynodon dactylon (L.) x C. transvaalensis (Burtt-Davy); and Cavalier and Palisades zoysiagrass, Zoysia japonica von Steudel and Z. matrella (L.) Merrill, respectively] represented a range in resistance to S. frugiperda. Differential recovery of larvae released as first instars reflected this gradient in resistance of Cavalier > or = Palisades > or = TifSport = TifEagle > or = 561- = Sea Isle-1 Larval recovery (percentage of initial number released) was greatest in May, less in July and August, and least in October, probably reflecting the increase in activity of on-site predators and disease pressure. Parasitism of the fall armyworm by the braconid Aleiodes laphygmae Viereck varied among turfgrass genotypes. Parasitism was greatest during July. In total, 20,400 first instars were placed in the field; 2,368 were recovered; 468 parasitoids were subsequently reared; 92.2% were A. laphygmae. In the field, the greatest percentage of reduction in S. frugiperda larvae by A. laphygmae occurred on the armyworm-susceptible seashore paspalums (51.9% on Sea Isle-1 in July). Cotesia marginiventris Cresson and Meteorus sp. also were reared from collected larvae. No parasitoids were reared from larvae collected from resistant Cavalier zoysiagrass. A. laphygmae and C. marginiventris were reared from larvae collected from the other five grass cultivars. No parasitoids of older larvae or pupae were observed.

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

DEFF Research Database (Denmark)

Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

2010-01-01

as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia.

Science.gov (United States)

Mukherjee, Angana; Bopp, Selina; Magistrado, Pamela; Wong, Wesley; Daniels, Rachel; Demas, Allison; Schaffner, Stephen; Amaratunga, Chanaki; Lim, Pharath; Dhorda, Mehul; Miotto, Olivo; Woodrow, Charles; Ashley, Elizabeth A; Dondorp, Arjen M; White, Nicholas J; Wirth, Dyann; Fairhurst, Rick; Volkman, Sarah K

2017-05-12

Artemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates with ring-stage survival under dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and emerging piperaquine resistance in Southeast Asia show that artemisinin combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical effectiveness, prompting investigation of drug resistance mechanisms and development of strategies to surmount emerging anti-malarial resistance. Sixty-eight parasites isolates with in vivo clearance data were obtained from two Tracking Resistance to Artemisinin Collaboration study sites in Cambodia, culture-adapted, and genotyped for pfkelch13 and other mutations including pfmdr1 copy number; and the RSA 0-3h survival rates and response to antimalarial drugs in vitro were measured for 36 of these isolates. Among these 36 parasites one isolate demonstrated increased ring-stage survival for a PfKelch13 mutation (D584V, RSA 0-3h  = 8%), previously associated with slow clearance but not yet tested in vitro. Several parasites exhibited increased ring-stage survival, yet lack pfkelch13 mutations, and one isolate showed evidence for piperaquine resistance. This study of 68 culture-adapted Plasmodium falciparum clinical isolates from Cambodia with known clearance values, associated the D584V PfKelch13 mutation with increased ring-stage survival and identified parasites that lack pfkelch13 mutations yet exhibit increased ring-stage survival. These data suggest mutations other than those found in pfkelch13 may be involved in conferring artemisinin resistance in P. falciparum. Piperaquine resistance was also detected among the same Cambodian samples, consistent with reports of emerging piperaquine resistance in the field. These culture-adapted parasites permit further investigation of mechanisms of both artemisinin and piperaquine

Elevated temperatures and long drought periods have a negative impact on survival and fitness of strongylid third stage larvae.

Science.gov (United States)

Knapp-Lawitzke, Friederike; von Samson-Himmelstjerna, Georg; Demeler, Janina

2016-04-01

In grazing cattle, infections with gastrointestinal nematodes pose some of the most important health threats and subclinical infections result in considerable production losses. While there is little doubt that climate change will affect grazing ruminants directly, mean temperature increases of ∼ 3°C and longer drought stress periods in summer may also influence the free-living stages of parasitic nematodes. Hostile climatic conditions reduce the number of L3s on pasture and therefore the refugium, which is expected to result in a higher selection pressure, accelerating development of resistance against anthelmintic drugs. The aim of the current experiments was to investigate the effects of drought stress and different temperature/humidity ranges over time on the survival and fitness of Cooperia oncophora L3s and their distribution in grass and soil under controlled conditions using a climate chamber. Grass containers inoculated with L3s were analysed after 1-6weeks using descriptive statistics as well as linear models. A large proportion of L3s was recovered from soil where fitness was also better preserved than on grass. Numbers and fitness of recovered L3s declined with duration in the climate chamber under both temperature profiles. However, the results of the linear models confirmed that higher temperatures (20-33°C versus 17-22.6°C) significantly impaired survival, distribution and fitness of L3s. Application of drought stress, known as another important factor, had a surprisingly smaller impact than its duration or higher temperatures. The climate chamber enabled exclusion of confounding factors and therefore accurate interpretation of the investigated climatic aspects. The obtained results highlight the relative importance of those factors, and will help to design better models for the population dynamics of L3s on pasture in the future. Additionally, the outcomes of these investigations may offer explanations regarding interdependencies of development

Host partitioning by parasites in an intertidal crustacean community.

Science.gov (United States)

Koehler, Anson V; Poulin, Robert

2010-10-01

Patterns of host use by parasites throughout a guild community of intermediate hosts can depend on several biological and ecological factors, including physiology, morphology, immunology, and behavior. We looked at parasite transmission in the intertidal crustacean community of Lower Portobello Bay, Dunedin, New Zealand, with the intent of: (1) mapping the flow of parasites throughout the major crustacean species, (2) identifying hosts that play the most important transmission role for each parasite, and (3) assessing the impact of parasitism on host populations. The most prevalent parasites found in 14 species of crustaceans (635 specimens) examined were the trematodes Maritrema novaezealandensis and Microphallus sp., the acanthocephalans Profilicollis spp., the nematode Ascarophis sp., and an acuariid nematode. Decapods were compatible hosts for M. novaezealandensis, while other crustaceans demonstrated lower host suitability as shown by high levels of melanized and immature parasite stages. Carapace thickness, gill morphology, and breathing style may contribute to the differential infection success of M. novaezealandensis and Microphallus sp. in the decapod species. Parasite-induced host mortality appears likely with M. novaezealandensis in the crabs Austrohelice crassa, Halicarcinus varius, Hemigrapsus sexdentatus, and Macrophthalmus hirtipes, and also with Microphallus sp. in A. crassa. Overall, the different parasite species make different use of available crustacean intermediate hosts and possibly contribute to intertidal community structure.

The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

Science.gov (United States)

Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

2017-02-01

The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; pcancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The genome and life-stage specific transcriptomes of Globodera pallida elucidate key aspects of plant parasitism by a cyst nematode

KAUST Repository

Cotton, James A

2014-03-03

Background: Globodera pallida is a devastating pathogen of potato crops, making it one of the most economically important plant parasitic nematodes. It is also an important model for the biology of cyst nematodes. Cyst nematodes and root-knot nematodes are the two most important plant parasitic nematode groups and together represent a global threat to food security. Results: We present the complete genome sequence of G. pallida, together with transcriptomic data from most of the nematode life cycle, particularly focusing on the life cycle stages involved in root invasion and establishment of the biotrophic feeding site. Despite the relatively close phylogenetic relationship with root-knot nematodes, we describe a very different gene family content between the two groups and in particular extensive differences in the repertoire of effectors, including an enormous expansion of the SPRY domain protein family in G. pallida, which includes the SPRYSEC family of effectors. This highlights the distinct biology of cyst nematodes compared to the root-knot nematodes that were, until now, the only sedentary plant parasitic nematodes for which genome information was available. We also present in-depth descriptions of the repertoires of other genes likely to be important in understanding the unique biology of cyst nematodes and of potential drug targets and other targets for their control. Conclusions: The data and analyses we present will be central in exploiting post-genomic approaches in the development of much-needed novel strategies for the control of G. pallida and related pathogens. 2014 Cotton et al.; licensee BioMed Central Ltd.

The Effect of Radiation Dose and Chemotherapy on Overall Survival in 237 Patients With Stage III Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Wang Li; Correa, Candace R.; Zhao Lujun; Hayman, James; Kalemkerian, Gregory P.; Lyons, Susan; Cease, Kemp; Brenner, Dean; Kong Fengming

2009-01-01

Purpose: To study the effects of radiation dose, chemotherapy, and their interaction in patients with unresectable or medically inoperable Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: A total of 237 consecutive Stage III NSCLC patients were evaluated. Median follow-up was 69.0 months. Patients were treated with radiation therapy (RT) alone (n = 106), sequential chemoradiation (n = 69), or concurrent chemoradiation (n = 62). The primary endpoint was overall survival (OS). Radiation dose ranged from 30 to 102.9 Gy (median 60 Gy), corresponding to a bioequivalent dose (BED) of 39 to 124.5 Gy (median 72 Gy). Results: The median OS of the entire cohort was 12.6 months, and 2- and 5-year survival rates were 22.4% and 10.0%, respectively. Multivariable Cox regression model demonstrated that Karnofsky performance status (p = 0.020), weight loss < 5% (p = 0.017), chemotherapy (yes vs. no), sequence of chemoradiation (sequential vs. concurrent; p < 0.001), and BED (p < 0.001) were significant predictors of OS. For patients treated with RT alone, sequential chemoradiation, and concurrent chemoradiation, median survival was 7.4, 14.9, and 15.8 months, and 5-year OS was 3.3%, 7.5%, and 19.4%, respectively (p < 0.001). The effect of higher radiation doses on survival was independent of whether chemotherapy was given. Conclusion: Radiation dose and use of chemotherapy are independent predictors of OS in Stage III NSCLC, and concurrent chemoradiation is associated with the best survival. There is no interaction between RT dose and chemotherapy.

Effects of a psychosocial intervention on survival among patients with stage I breast and prostate cancer: a matched case-control study.

Science.gov (United States)

Shrock, D; Palmer, R F; Taylor, B

1999-05-01

Psychosocial factors have been linked to the development and progression of cancer and shown to be relevant in cancer care. However, the evidence that psychosocial interventions affect cancer survival is less conclusive. Few methodologically sound studies have addressed this issue. To investigate the effects of a 6-week psychosocial intervention on survival among patients with stage I breast and prostate cancer. Matched case-control. 3 rural hospitals or cancer centers in central Pennsylvania. 21 breast and 29 prostate stage I cancer patients (treatment group) matched with 74 breast and 65 prostate stage I cancer patients from the same hospitals who did not receive the intervention (control group). Six 2-hour health psychology classes conducted by a licensed staff psychologist. Survival time was compared between the 2 groups and with national norms. The intervention group lived significantly longer than did matched controls. At 4- to 7-year follow-up (median = 4.2 years), none of the breast cancer patients in the intervention group died, whereas 12% of those in the control group died. Twice as many matched-control prostate cancer patients died compared with those in the intervention group (28% vs 14%). Control group survival was similar to national norms. These results are consistent with prior clinical trials and suggest that short-term psychosocial interventions that encourage the expression of emotions, provide social support, and teach coping skills can influence survival among cancer patients. However, self-selection bias cannot be ruled out as an alternative explanation for the results. These interventions merit further consideration and research.

Transgenic Analysis of the Leishmania MAP Kinase MPK10 Reveals an Auto-inhibitory Mechanism Crucial for Stage-Regulated Activity and Parasite Viability

DEFF Research Database (Denmark)

Cayla, M.; Rachidi, N.; Leclercq, O.

2014-01-01

Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell infection. The signaling mechanisms underlying parasite development remain largely elusive even...... though Leishmania mitogen-activated protein kinases (MAPKs) have been linked previously to environmentally induced differentiation and virulence. Here, we unravel highly unusual regulatory mechanisms for Leishmania MAP kinase 10 (MPK10). Using a transgenic approach, we demonstrate that MPK10 is stage...... at position 395 that could be implicated in kinase regulation. Finally, we uncovered a feedback loop that limits MPK10 activity through dephosphorylation of the tyrosine residue of the TxY motif. Together our data reveal novel aspects of protein kinase regulation in Leishmania, and propose MPK10...

Model for breast cancer survival: relative prognostic roles of axillary nodal status, TNM stage, estrogen receptor concentration, and tumor necrosis.

Science.gov (United States)

Shek, L L; Godolphin, W

1988-10-01

The independent prognostic effects of certain clinical and pathological variables measured at the time of primary diagnosis were assessed with Cox multivariate regression analysis. The 859 patients with primary breast cancer, on which the proportional hazards model was based, had a median follow-up of 60 months. Axillary nodal status (categorized as N0, N1-3 or N4+) was the most significant and independent factor in overall survival, but inclusion of TNM stage, estrogen receptor (ER) concentration and tumor necrosis significantly improved survival predictions. Predictions made with the model showed striking subset survival differences within stage: 5-year survival from 36% (N4+, loge[ER] = 0, marked necrosis) to 96% (N0, loge[ER] = 6, no necrosis) in TNM I, and from 0 to 70% for the same categories in TNM IV. Results of the model were used to classify patients into four distinct risk groups according to a derived hazard index. An 8-fold variation in survival was seen with the highest (greater than 3) to lowest index values (less than 1). Each hazard index level included patients with varied combinations of the above factors, but could be considered to denote the same degree of risk of breast cancer mortality. A model with ER concentration, nodal status, and tumor necrosis was found to best predict survival after disease recurrence in 369 patients, thus confirming the enduring biological significance of these factors.

Survival benefit of adjuvant radiotherapy in stage III and IV bladder cancer: results of 170 patients

Directory of Open Access Journals (Sweden)

Bayoumi Y

2014-11-01

Full Text Available Yasser Bayoumi,1 Tarek Heikal,2 Hossam Darweish2 1Radiation Oncology, National Cancer Institute, Cairo University, Giza, Egypt; 2Medical Oncology, Damietta Cancer Institute, Ministry of Health, Damietta, Egypt Background: Radical cystectomy (RC with or without neoadjuvant chemotherapy is the standard treatment for muscle-invasive bladder cancers. However, the locoregional recurrence rate is still significantly higher for locally advanced cases post-RC. The underuse of postoperative radiotherapy (PORT in such cases after RC is related mainly to a lack of proven survival benefit. Here we are reporting our long-term Egyptian experience with bladder cancer patients treated with up-front RC with or without conformal PORT. Patients and methods: This retrospective study included 170 locally advanced bladder cancer (T3–T4, N0/N1, M0 patients who had RC performed with or without PORT at Damietta Cancer Institute during the period of 1998–2006. The treatment outcomes and toxicity profile of PORT were evaluated and compared with those of a non-PORT group of patients. Results: Ninety-two patients received PORT; 78 did not. At median follow-up of 47 months (range, 17–77 months, 33% locoregional recurrences were seen in the PORT group versus 55% in the non-PORT group (P<0.001. The overall distant metastasis rate in the whole group was 39%, with no difference between the two groups. The 5-year disease-free survival for the whole group of patients was 53%±11%, which was significantly affected by additional PORT, and 65%±13% compared with 40%±9% for the non-PORT group (P=0.04. The pathological subtypes did not affect 5-year disease-free survival significantly (P=0.9. The 5-year overall survival was 44%±10%. Using multivariate analysis, PORT, stage, and extravesical extension (positive surgical margins were found to be important prognostic factors for locoregional control. Stage and lymph node status were important prognosticators for distant metastasis

Juvenile Salmonid Parasite Data - Ocean Survival of Salmonids

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — A study to evaluate the role of changing ocean conditions on growth and survival of juvenile salmon from the Columbia River basin as they enter the Columbia River...

Gray fox (Urocyon cinereoargenteus parasite diversity in central Mexico

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Norma Hernández-Camacho

2016-08-01

Full Text Available Mexico has a long history of parasitological studies in communities of vertebrates. However, the mega diversity of the country makes fauna inventories an ongoing priority. Presently, there is little published on the parasite fauna of gray foxes (Urocyon cinereoargenteus Schereber, 1775 and this study provides new records of parasites for gray foxes in central Mexico. It is a continuation of a series of previous parasitological studies conducted with this carnivore in Mexico from 2003 to the present. A total of 24 foxes in the Parque Nacional El Cimatario (PANEC were trapped, anaesthetized, and parasites recovered. The species found were Dirofilaria immitis, Ctenocephalides canis, C. felis, Euhoplopsillus glacialis affinis (first report for gray foxes in Mexico Pulex simulants, and Ixodes sp. Three additional gray fox carcasses were necropsied and the parasites collected were adult nematodes Physaloptera praeputialis and Toxocara canis. The intensive study of the gray fox population selected for the 2013–2015 recent period allowed for a two-fold increase in the number of parasite species recorded for this carnivore since 2003 (nine to 18 parasite species, mainly recording parasitic arthropods, Dirofilaria immitis filariae and adult nematodes. The parasite species recorded are generalists that can survive in anthropic environments; which is characteristic of the present ecological scenario in central Mexico. The close proximity of the PANEC to the city of Santiago de Queretaro suggests possible parasite transmission between the foxes and domestic and feral dogs. Furthermore, packs of feral dogs in the PANEC might have altered habitat use by foxes, with possible impacts on transmission.

End-stage renal disease and survival in people with diabetes: a national database linkage study

OpenAIRE

Bell, S.; Fletcher, E.H.; Brady, I.; Looker, H.C.; Levin, D.; Joss, N.; Traynor, J.P.; Metcalfe, W.; Conway, B.; Livingstone, S.; Leese, G.; Philip, S.; Wild, S.; Halbesma, N.; Sattar, N.

2014-01-01

Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT).Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival.Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration...

Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

International Nuclear Information System (INIS)

Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

2009-01-01

Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

Rapid evolution of parasite life history traits on an expanding range-edge.

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Kelehear, Crystal; Brown, Gregory P; Shine, Richard

2012-04-01

Parasites of invading species undergoing range advance may be exposed to powerful new selective forces. Low host density in range-edge populations hampers parasite transmission, requiring the parasite to survive longer periods in the external environment before encountering a potential host. These conditions should favour evolutionary shifts in offspring size to maximise parasite transmission. We conducted a common-garden experiment to compare life history traits among seven populations of the nematode lungworm (Rhabdias pseudosphaerocephala) spanning from the parasite population core to the expanding range-edge in invasive cane toads (Rhinella marina) in tropical Australia. Compared to conspecifics from the population core, nematodes from the range-edge exhibited larger eggs, larger free-living adults and larger infective larvae, and reduced age at maturity in parasitic adults. These results support a priori predictions regarding adaptive changes in offspring size as a function of invasion history, and suggest that parasite life history traits can evolve rapidly in response to the selective forces exerted by a biological invasion. © 2012 Blackwell Publishing Ltd/CNRS.

Effect of a Shortened Duration of FOLFOX Chemotherapy on the Survival Rate of Patients with Stage II and III Colon Cancer.

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Ji, Woong Bae; Hong, Kwang Dae; Kim, Jung-Sik; Joung, Sung-Yup; Um, Jun Won; Min, Byung-Wook

2018-01-01

FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer. We compared the 5-year survival rates and the occurrence of complications in patients who completed only 8 cycles of FOLFOX chemotherapy with patients who completed 12 cycles of chemotherapy. Among 188 patients who underwent adjuvant FOLFOX chemotherapy for stage II or III colon cancer, 83 (44.1%) completed 6 months of FOLFOX chemotherapy and 64 (34.0%) patients discontinued after 4 months of chemotherapy. The 5-year overall survival and disease-free survival rates did not show a significant difference. Patients in the 6-month group had peripheral neuropathy more frequently (p = 0.028). Five-year overall and disease-free survival were not significantly different between the 2 groups. Large-scale prospective studies are necessary for the analysis of complications and survival rates. © 2017 S. Karger AG, Basel.

Pitting of malaria parasites and spherocyte formation

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Gichuki Charity W

2006-07-01

Full Text Available Abstract Background A high prevalence of spherocytes was detected in blood smears of children enrolled in a case control study conducted in the malaria holoendemic Lake Victoria basin. It was speculated that the spherocytes reflect intraerythrocytic removal of malarial parasites with a concurrent removal of RBC membrane through a process analogous to pitting of intraerythrocytic inclusion bodies. Pitting and re-circulation of RBCs devoid of malaria parasites could be a host mechanism for parasite clearance while minimizing the anaemia that would occur were the entire parasitized RBC removed. The prior demonstration of RBCs containing ring-infected erythrocyte surface antigen (pf 155 or RESA but no intracellular parasites, support the idea of pitting. Methods An in vitro model was developed to examine the phenomenon of pitting and spherocyte formation in Plasmodium falciparum infected RBCs (iRBC co-incubated with human macrophages. In vivo application of this model was evaluated using blood specimens from patients attending Kisumu Ditrict Hospital. RBCs were probed with anti-RESA monoclonal antibody and a DNA stain (propidium iodide. Flow cytometry and fluorescent microscopy was used to compare RBCs containing both the antigen and the parasites to those that were only RESA positive. Results Co-incubation of iRBC and tumor necrosis factor-alpha activated macrophages led to pitting (14% ± 1.31% macrophages with engulfed trophozoites as opposed to erythrophagocytosis (5.33% ± 0.95% (P Conclusion It is proposed that in malaria holoendemic areas where prevalence of asexual stage parasites approaches 100% in children, RBCs with pitted parasites are re-circulated and pitting may produce spherocytes.

Effects of shortened host life span on the evolution of parasite life history and virulence in a microbial host-parasite system

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Koella Jacob C

2009-03-01

Full Text Available Abstract Background Ecological factors play an important role in the evolution of parasite exploitation strategies. A common prediction is that, as shorter host life span reduces future opportunities of transmission, parasites compensate with an evolutionary shift towards earlier transmission. They may grow more rapidly within the host, have a shorter latency time and, consequently, be more virulent. Thus, increased extrinsic (i.e., not caused by the parasite host mortality leads to the evolution of more virulent parasites. To test these predictions, we performed a serial transfer experiment, using the protozoan Paramecium caudatum and its bacterial parasite Holospora undulata. We simulated variation in host life span by killing hosts after 11 (early killing or 14 (late killing days post inoculation; after killing, parasite transmission stages were collected and used for a new infection cycle. Results After 13 cycles (≈ 300 generations, parasites from the early-killing treatment were less infectious, but had shorter latency time and higher virulence than those from the late-killing treatment. Overall, shorter latency time was associated with higher parasite loads and thus presumably with more rapid within-host replication. Conclusion The analysis of the means of the two treatments is thus consistent with theory, and suggests that evolution is constrained by trade-offs between virulence, transmission and within-host growth. In contrast, we found little evidence for such trade-offs across parasite selection lines within treatments; thus, to some extent, these traits may evolve independently. This study illustrates how environmental variation (experienced by the host can lead to the evolution of distinct parasite strategies.

[Long-term outcome with end-stage renal disease - survival is not enough: does dialysis or kidney transplantation matter?].

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Schulz, K-H; Thaiss, F

2012-04-01

Patients with end-stage renal disease require renal replacement therapy with either dialysis or kidney transplantation. Survival and quality of life (QoL) after transplantation are superior to chronic dialysis. Early living donor kidney transplantation is best for patient and graft survival. Preemptive living-related kidney transplantation therefore is the best medical treatment option for these patients. Patients with end-stage renal disease suffer from multiple physical and psychological complaints. The prevalence of depressive disorders is 20-25% in this population. Studies on QoL in children after kidney transplantation show a reduced physical QoL, but an overall good psychological QoL. Alarming results of numerous studies are the high non-adherence rates in adolescents. Especially exercise interventions during dialysis and after kidney transplantation show promising results. Whether QoL of patients will improve with new approaches to immunosuppressive therapy remains to be evaluated in future studies.

Parasites Promote and When Might They Constrain Ecological Speciation?

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Anssi Karvonen

2012-01-01

Full Text Available Research on speciation and adaptive radiation has flourished during the past decades, yet factors underlying initiation of reproductive isolation often remain unknown. Parasites represent important selective agents and have received renewed attention in speciation research. We review the literature on parasite-mediated divergent selection in context of ecological speciation and present empirical evidence for three nonexclusive mechanisms by which parasites might facilitate speciation: reduced viability or fecundity of immigrants and hybrids, assortative mating as a pleiotropic by-product of host adaptation, and ecologically-based sexual selection. We emphasise the lack of research on speciation continuums, which is why no study has yet made a convincing case for parasite driven divergent evolution to initiate the emergence of reproductive isolation. We also point interest towards selection imposed by single versus multiple parasite species, conceptually linking this to strength and multifariousness of selection. Moreover, we discuss how parasites, by manipulating behaviour or impairing sensory abilities of hosts, may change the form of selection that underlies speciation. We conclude that future studies should consider host populations at variable stages of the speciation process, and explore recurrent patterns of parasitism and resistance that could pinpoint the role of parasites in imposing the divergent selection that initiates ecological speciation.

Monoclonal Antibodies to Intracellular Stages of Cryptosporidium parvum Define Life Cycle Progression In Vitro.

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Wilke, Georgia; Ravindran, Soumya; Funkhouser-Jones, Lisa; Barks, Jennifer; Wang, Qiuling; VanDussen, Kelli L; Stappenbeck, Thaddeus S; Kuhlenschmidt, Theresa B; Kuhlenschmidt, Mark S; Sibley, L David

2018-06-27

Among the obstacles hindering Cryptosporidium research is the lack of an in vitro culture system that supports complete life development and propagation. This major barrier has led to a shortage of widely available anti- Cryptosporidium antibodies and a lack of markers for staging developmental progression. Previously developed antibodies against Cryptosporidium were raised against extracellular stages or recombinant proteins, leading to antibodies with limited reactivity across the parasite life cycle. Here we sought to create antibodies that recognize novel epitopes that could be used to define intracellular development. We identified a mouse epithelial cell line that supported C. parvum growth, enabling immunization of mice with infected cells to create a bank of monoclonal antibodies (MAbs) against intracellular parasite stages while avoiding the development of host-specific antibodies. From this bank, we identified 12 antibodies with a range of reactivities across the parasite life cycle. Importantly, we identified specific MAbs that can distinguish different life cycle stages, such as trophozoites, merozoites, type I versus II meronts, and macrogamonts. These MAbs provide valuable tools for the Cryptosporidium research community and will facilitate future investigation into parasite biology. IMPORTANCE Cryptosporidium is a protozoan parasite that causes gastrointestinal disease in humans and animals. Currently, there is a limited array of antibodies available against the parasite, which hinders imaging studies and makes it difficult to visualize the parasite life cycle in different culture systems. In order to alleviate this reagent gap, we created a library of novel antibodies against the intracellular life cycle stages of Cryptosporidium We identified antibodies that recognize specific life cycle stages in distinctive ways, enabling unambiguous description of the parasite life cycle. These MAbs will aid future investigation into Cryptosporidium biology and

Breast implants following mastectomy in women with early-stage breast cancer: prevalence and impact on survival

International Nuclear Information System (INIS)

Le, Gem M; O'Malley, Cynthia D; Glaser, Sally L; Lynch, Charles F; Stanford, Janet L; Keegan, Theresa HM; West, Dee W

2005-01-01

Few studies have examined the effect of breast implants after mastectomy on long-term survival in breast cancer patients, despite growing public health concern over potential long-term adverse health effects. We analyzed data from the Surveillance, Epidemiology and End Results Breast Implant Surveillance Study conducted in San Francisco–Oakland, in Seattle–Puget Sound, and in Iowa. This population-based, retrospective cohort included women younger than 65 years when diagnosed with early or unstaged first primary breast cancer between 1983 and 1989, treated with mastectomy. The women were followed for a median of 12.4 years (n = 4968). Breast implant usage was validated by medical record review. Cox proportional hazards models were used to estimate hazard rate ratios for survival time until death due to breast cancer or other causes for women with and without breast implants, adjusted for relevant patient and tumor characteristics. Twenty percent of cases received postmastectomy breast implants, with silicone gel-filled implants comprising the most common type. Patients with implants were younger and more likely to have in situ disease than patients not receiving implants. Risks of breast cancer mortality (hazard ratio, 0.54; 95% confidence interval, 0.43–0.67) and nonbreast cancer mortality (hazard ratio, 0.59; 95% confidence interval, 0.41–0.85) were lower in patients with implants than in those patients without implants, following adjustment for age and year of diagnosis, race/ethnicity, stage, tumor grade, histology, and radiation therapy. Implant type did not appear to influence long-term survival. In a large, population-representative sample, breast implants following mastectomy do not appear to confer any survival disadvantage following early-stage breast cancer in women younger than 65 years old

Timing of host feeding drives rhythms in parasite replication

KAUST Repository

Prior, Kimberley F.

2018-02-26

Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the host’s peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the host’s peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new

Timing of host feeding drives rhythms in parasite replication

KAUST Repository

Prior, Kimberley F

2017-12-07

Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the host\\'s peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the host\\'s peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new

Dynamics of sterol synthesis during development of Leishmania spp. parasites to their virulent form.

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Yao, Chaoqun; Wilson, Mary E

2016-04-12

The Leishmania spp. protozoa, the causative agents of the "neglected" tropical disease leishmaniasis, are transmitted to mammals by sand fly vectors. Within the sand fly, parasites transform from amastigotes to procyclic promastigotes, followed by development of virulent (metacyclic) promastigote forms. The latter are infectious to mammalian hosts. Biochemical components localized in the parasite plasma membrane such as proteins and sterols play a pivotal role in Leishmania pathogenesis. Leishmania spp. lack the enzymes for cholesterol synthesis, and the dynamics of sterol acquisition and biosynthesis in parasite developmental stages are not understood. We hypothesized that dynamic changes in sterol composition during metacyclogenesis contribute to the virulence of metacyclic promastigotes. Sterols were extracted from logarithmic phase or metacyclic promastigotes grown in liquid culture with or without cholesterol, and analyzed qualitatively and quantitatively by gas chromatograph-mass spectrometry (GC-MS). TriTrypDB was searched for identification of genes involved in Leishmania sterol biosynthetic pathways. In total nine sterols were identified. There were dynamic changes in sterols during promastigote metacyclogenesis. Cholesterol in the culture medium affected sterol composition in different parasite stages. There were qualitative and relative quantitative differences between the sterol content of virulent versus avirulent parasite strains. A tentative sterol biosynthetic pathway in Leishmania spp. promastigotes was identified. Significant differences in sterol composition were observed between promastigote stages, and between parasites exposed to different extracellular cholesterol in the environment. These data lay the foundation for further investigating the role of sterols in the pathogenesis of Leishmania spp. infections.

Blood parasites in reptiles imported to Germany.

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Halla, Ursula; Ursula, Halla; Korbel, Rüdiger; Rüdiger, Korbel; Mutschmann, Frank; Frank, Mutschmann; Rinder, Monika; Monika, Rinder

2014-12-01

Though international trade is increasing, the significance of imported reptiles as carriers of pathogens with relevance to animal and human health is largely unknown. Reptiles imported to Germany were therefore investigated for blood parasites using light microscopy, and the detected parasites were morphologically characterized. Four hundred ten reptiles belonging to 17 species originating from 11 Asian, South American and African countries were included. Parasites were detected in 117 (29%) of individual reptiles and in 12 species. Haemococcidea (Haemogregarina, Hepatozoon, Schellackia) were found in 84% of snakes (Python regius, Corallus caninus), 20% of lizards (Acanthocercus atricollis, Agama agama, Kinyongia fischeri, Gekko gecko) and 50% of turtles (Pelusios castaneus). Infections with Hematozoea (Plasmodium, Sauroplasma) were detected in 14% of lizards (Acanthocercus atricollis, Agama agama, Agama mwanzae, K. fischeri, Furcifer pardalis, Xenagama batillifera, Acanthosaura capra, Physignathus cocincinus), while those with Kinetoplastea (Trypanosoma) were found in 9% of snakes (Python regius, Corallus caninus) and 25 % of lizards (K. fischeri, Acanthosaura capra, G. gecko). Nematoda including filarial larvae parasitized in 10% of lizards (Agama agama, Agama mwanzae, K. fischeri, Fu. pardalis, Physignathus cocincinus). Light microscopy mostly allowed diagnosis of the parasites' genus, while species identification was not possible because of limited morphological characteristics available for parasitic developmental stages. The investigation revealed a high percentage of imported reptiles being carriers of parasites while possible vectors and pathogenicity are largely unknown so far. The spreading of haemoparasites thus represents an incalculable risk for pet reptiles, native herpetofauna and even human beings.

Translational Control in Plasmodium and Toxoplasma Parasites

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Joyce, Bradley R.; Sullivan, William J.; Nussenzweig, Victor

2013-01-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis. PMID:23243065

Translational control in Plasmodium and toxoplasma parasites.

Science.gov (United States)

Zhang, Min; Joyce, Bradley R; Sullivan, William J; Nussenzweig, Victor

2013-02-01

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α∼P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α∼P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.

Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

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Qinghua ZHOU

2011-02-01

Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

Results and survival after photodynamic therapy in early-stage esophageal carcinoma

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Spinelli, Pasquale; Mancini, Andrea; dal Fante, Marco; Meroni, Emmanuele; Jasinskas, Algirdas

1996-01-01

From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.

Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal.

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Agar, Nita Sally; Wedgeworth, Emma; Crichton, Siobhan; Mitchell, Tracey J; Cox, Michael; Ferreira, Silvia; Robson, Alistair; Calonje, Eduardo; Stefanato, Catherine M; Wain, Elizabeth Mary; Wilkins, Bridget; Fields, Paul A; Dean, Alan; Webb, Katherine; Scarisbrick, Julia; Morris, Stephen; Whittaker, Sean J

2010-11-01

We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal. Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models. The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival. This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.

The influence of marital status on the stage at diagnosis, treatment, and survival of adult patients with gastric cancer: a population-based study.

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Zhang, Jieyun; Gan, Lu; Wu, Zhenhua; Yan, Shican; Liu, Xiyu; Guo, Weijian

2017-04-04

Marital status was reported as a prognostic factor in many cancers. However, its role in gastric cancer (GC) hasn't been thoroughly explored. In this study, we aimed to investigate the effect of marital status on survival, stage, treatment, and survival in subgroups. We used the Surveillance, Epidemiology and End Results (SEER) database and identified 16910 GC patients. These patients were categorized into married (58.44%) and unmarred (41.56%) groups. Pearson chi-square, Wilcoxon-Mann-Whitney, Log-rank, multivariate Cox regression, univariate and multivariate binomial or multinomial logistic regression analysis were used in our analysis. Subgroup analyses of married versus unmarried patients were summarized in a forest plot. Married patients had better 5-year overall survival (OS) (32.09% VS 24.61%, PVS 32.79%, Punmarried ones. Then we studied several underlying mechanisms. Firstly, married patients weren't in earlier stage at diagnosis (P=0.159). Secondly, married patients were more likely to receive surgery (P unmarried. Thirdly, in subgroup analyses, married patients still had survival advantage in subgroups with stage II-IV and no radiotherapy. These results showed that marital status was an independently prognostic factor for both OS and CSS in GC patients. Undertreatment and lack of social support in unmarried patients were potential explanations. With the knowledge of heterogeneous effects of marriage in subgroups, we can target unmarried patients with better social support, especially who are diagnosed at late stage and undergo no treatment.

Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model.

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Singh, Kawaljit; Okombo, John; Brunschwig, Christel; Ndubi, Ferdinand; Barnard, Linley; Wilkinson, Chad; Njogu, Peter M; Njoroge, Mathew; Laing, Lizahn; Machado, Marta; Prudêncio, Miguel; Reader, Janette; Botha, Mariette; Nondaba, Sindisiwe; Birkholtz, Lyn-Marie; Lauterbach, Sonja; Churchyard, Alisje; Coetzer, Theresa L; Burrows, Jeremy N; Yeates, Clive; Denti, Paolo; Wiesner, Lubbe; Egan, Timothy J; Wittlin, Sergio; Chibale, Kelly

2017-02-23

Further structure-activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of hemozoin formation possibly contributes to the mechanism of action.

Floral Volatiles in Parasitic Plants of the Orobanchaceae. Ecological and Taxonomic Implications

Science.gov (United States)

Tóth, Peter; Undas, Anna K.; Verstappen, Francel; Bouwmeester, Harro

2016-01-01

The holoparasitic broomrapes, Orobanche spp. and Phelipanche spp. (Orobanchaceae), are root parasites that completely depend on a host plant for survival and reproduction. There is considerable controversy on the taxonomy of this biologically and agronomically important family. Flowers of over 25 parasitic Orobanchaceae and a number of close, parasitic and non-parasitic, relatives emitted a complex blend of volatile organic compounds (VOCs), consisting of over 130 VOCs per species. Floral VOC blend-based phylogeny supported the known taxonomy in internal taxonomic grouping of genus and eliminated the uncertainty in some taxonomical groups. Moreover, phylogenetic analysis suggested separation of the broomrapes into two main groups parasitizing annual and perennial hosts, and for the annual hosts, into weedy and non-weedy broomrapes. We conclude that floral VOCs are a significant tool in species identification and possibly even in defining new species and can help to improve controversial taxonomy in the Orobanchaceae. PMID:27014329

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

International Nuclear Information System (INIS)

Wada, Nobuyuki; Rino, Yasushi; Masuda, Munetaka; Ito, Koichi; Sugino, Kiminori; Mimura, Takashi; Nagahama, Mitsuji; Kitagawa, Wataru; Shibuya, Hiroshi; Ohkuwa, Keiko; Nakayama, Hirotaka; Hirakawa, Shohei

2009-01-01

To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients

Disparities in cancer stage at diagnosis and survival of Aboriginal and non-Aboriginal South Australians.

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Banham, David; Roder, David; Keefe, Dorothy; Farshid, Gelareh; Eckert, Marion; Cargo, Margaret; Brown, Alex

2017-06-01

This study tested the utility of retrospectively staging cancer registry data for comparing stage and stage-specific survivals of Aboriginal and non-Aboriginal people. Differences by area level factors were also explored. This test dataset comprised 950 Aboriginal cases and all other cases recorded on the South Australian cancer registry with a 1977-2010 diagnosis. A sub-set of 777 Aboriginal cases diagnosed in 1990-2010 were matched with randomly selected non-Aboriginal cases by year of birth, diagnostic year, sex, and primary site of cancer. Competing risk regression summarised associations of Aboriginal status, stage, and geographic attributes with risk of cancer death. Aboriginal cases were 10 years younger at diagnosis, more likely to present in recent diagnostic years, to be resident of remote areas, and have primary cancer sites of head & neck, lung, liver and cervix. Risk of cancer death was associated in the matched analysis with more advanced stage at diagnosis. More Aboriginal than non-Aboriginal cases had distant metastases at diagnosis (31.3% vs 22.0, pAboriginal residents had higher risks of cancer death than Aboriginal residents of metropolitan areas. Non-Aboriginal cases had the lowest risk of cancer death. Retrospective staging proved to be feasible using registry data. Results indicated more advanced stages for Aboriginal than matched non-Aboriginal cases. Aboriginal people had higher risks of cancer death, which persisted after adjusting for stage, and applied irrespective of remoteness of residence, with highest risk of death occurring among Aboriginal people from remote areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium falciparum.

Science.gov (United States)

Niemand, J; Louw, A I; Birkholtz, L; Kirk, K

2012-09-01

Polyamines and the enzymes involved in their biosynthesis are present at high levels in rapidly proliferating cells, including cancer cells and protozoan parasites. Inhibition of polyamine biosynthesis in asexual blood-stage malaria parasites causes cytostatic arrest of parasite development under in vitro conditions, but does not cure infections in vivo. This may be due to replenishment of the parasite's intracellular polyamine pool via salvage of exogenous polyamines from the host. However, the mechanism(s) of polyamine uptake by the intraerythrocytic parasite are not well understood. In this study, the uptake of the polyamines, putrescine and spermidine, into Plasmodium falciparum parasites functionally isolated from their host erythrocyte was investigated using radioisotope flux techniques. Both putrescine and spermidine were taken up into isolated parasites via a temperature-dependent process that showed cross-competition between different polyamines. There was also some inhibition of polyamine uptake by basic amino acids. Inhibition of polyamine biosynthesis led to an increase in the total amount of putrescine and spermidine taken up from the extracellular medium. The uptake of putrescine and spermidine by isolated parasites was independent of extracellular Na(+) but increased with increasing external pH. Uptake also showed a marked dependence on the parasite's membrane potential, decreasing with membrane depolarization and increasing with membrane hyperpolarization. The data are consistent with polyamines being taken up into the parasite via an electrogenic uptake process, energised by the parasite's inwardly negative membrane potential. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Individualized Prediction of Overall Survival After Postoperative Radiation Therapy in Patients With Early-Stage Cervical Cancer: A Korean Radiation Oncology Group Study (KROG 13-03)

International Nuclear Information System (INIS)

Lee, Hyun Jin; Han, Seungbong; Kim, Young Seok; Nam, Joo-Hyun; Kim, Hak Jae; Kim, Jae Weon; Park, Won; Kim, Byoung-Gie; Kim, Jin Hee; Cha, Soon Do; Kim, Juree; Lee, Ki-Heon; Yoon, Mee Sun

2013-01-01

Purpose: A nomogram is a predictive statistical model that generates the continuous probability of a clinical event such as death or recurrence. The aim of the study was to construct a nomogram to predict 5-year overall survival after postoperative radiation therapy for stage IB to IIA cervical cancer. Methods and Materials: The clinical data from 1702 patients with early-stage cervical cancer, treated at 10 participating hospitals from 1990 to 2011, were reviewed to develop a prediction nomogram based on the Cox proportional hazards model. Demographic, clinical, and pathologic variables were included and analyzed to formulate the nomogram. The discrimination and calibration power of the model was measured using a concordance index (c-index) and calibration curve. Results: The median follow-up period for surviving patients was 75.6 months, and the 5-year overall survival probability was 87.1%. The final model was constructed using the following variables: age, number of positive pelvic lymph nodes, parametrial invasion, lymphovascular invasion, and the use of concurrent chemotherapy. The nomogram predicted the 5-year overall survival with a c-index of 0.69, which was superior to the predictive power of the International Federation of Gynecology and Obstetrics (FIGO) staging system (c-index of 0.54). Conclusions: A survival-predicting nomogram that offers an accurate level of prediction and discrimination was developed based on a large multi-center study. The model may be more useful than the FIGO staging system for counseling individual patients regarding prognosis

Individualized Prediction of Overall Survival After Postoperative Radiation Therapy in Patients With Early-Stage Cervical Cancer: A Korean Radiation Oncology Group Study (KROG 13-03)

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Lee, Hyun Jin [Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Han, Seungbong [Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Kim, Young Seok, E-mail: ysk@amc.seoul.kr [Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Nam, Joo-Hyun [Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae [Department of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Jae Weon [Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul (Korea, Republic of); Park, Won [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Byoung-Gie [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jin Hee [Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Cha, Soon Do [Department of Obstetrics and Gynecology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Kim, Juree [Department of Radiation Oncology, Cheil General Hospital and Women' s Healthcare Center, Kwandong University, College of Medicine, Seoul (Korea, Republic of); Lee, Ki-Heon [Department of Obstetrics and Gynecology, Cheil General Hospital and Women' s Healthcare Center, Kwandong University, College of Medicine, Seoul (Korea, Republic of); Yoon, Mee Sun [Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Jeollanam-do (Korea, Republic of); and others

2013-11-15

Purpose: A nomogram is a predictive statistical model that generates the continuous probability of a clinical event such as death or recurrence. The aim of the study was to construct a nomogram to predict 5-year overall survival after postoperative radiation therapy for stage IB to IIA cervical cancer. Methods and Materials: The clinical data from 1702 patients with early-stage cervical cancer, treated at 10 participating hospitals from 1990 to 2011, were reviewed to develop a prediction nomogram based on the Cox proportional hazards model. Demographic, clinical, and pathologic variables were included and analyzed to formulate the nomogram. The discrimination and calibration power of the model was measured using a concordance index (c-index) and calibration curve. Results: The median follow-up period for surviving patients was 75.6 months, and the 5-year overall survival probability was 87.1%. The final model was constructed using the following variables: age, number of positive pelvic lymph nodes, parametrial invasion, lymphovascular invasion, and the use of concurrent chemotherapy. The nomogram predicted the 5-year overall survival with a c-index of 0.69, which was superior to the predictive power of the International Federation of Gynecology and Obstetrics (FIGO) staging system (c-index of 0.54). Conclusions: A survival-predicting nomogram that offers an accurate level of prediction and discrimination was developed based on a large multi-center study. The model may be more useful than the FIGO staging system for counseling individual patients regarding prognosis.

Blood protein turnover in parasitized ruminants. The influence of host nutrition

International Nuclear Information System (INIS)

Dargie, J.D.

1981-01-01

Ruminants infected with helminth or protozoal parasites generally become anaemic and hypoalbuminaemic, as well as losing their appetite. Since feed intake plays an important part in determining blood protein levels, it is necessary, when attempting to determine the mechanisms by which parasites cause anaemia and hypoalbuminaemia, to differentiate between the effects of feed intake per se and the specific effects of the parasite on blood protein turnover. This can be done by a variety of radioisotope techniques using infected and pair-fed control animals. Additionally, animals on a poor plane of nutrition suffer more from parasitism than those which are well fed. To understand the reason for this, it is necessary to determine whether diet influences susceptibility to parasite establishment or survival, and/or susceptibility to the metabolic consequences of parasitism. Described here is the current state of knowledge on the interaction between host nutrition and susceptibility to parasitic infection and parasitic disease processes, with particular reference to anaemia and hypoalbuminaemia. It is concluded that there is little evidence that nutrition has a significant bearing on resistance or susceptibility to infection, but that it does not have a profound influence on the ability of animals to withstand the pathogenic effects of parasites. The reasons for this are discussed in detail, but the principal benefit of a good plane of nutrition is that it enables the synthetic machinery of the host to keep pace with the concurrent parasite-induced hypercatabolism of blood proteins. (author)

Advances in the application of genetic manipulation methods to apicomplexan parasites.

Science.gov (United States)

Suarez, C E; Bishop, R P; Alzan, H F; Poole, W A; Cooke, B M

2017-10-01

Apicomplexan parasites such as Babesia, Theileria, Eimeria, Cryptosporidium and Toxoplasma greatly impact animal health globally, and improved, cost-effective measures to control them are urgently required. These parasites have complex multi-stage life cycles including obligate intracellular stages. Major gaps in our understanding of the biology of these relatively poorly characterised parasites and the diseases they cause severely limit options for designing novel control methods. Here we review potentially important shared aspects of the biology of these parasites, such as cell invasion, host cell modification, and asexual and sexual reproduction, and explore the potential of the application of relatively well-established or newly emerging genetic manipulation methods, such as classical transfection or gene editing, respectively, for closing important gaps in our knowledge of the function of specific genes and proteins, and the biology of these parasites. In addition, genetic manipulation methods impact the development of novel methods of control of the diseases caused by these economically important parasites. Transient and stable transfection methods, in conjunction with whole and deep genome sequencing, were initially instrumental in improving our understanding of the molecular biology of apicomplexan parasites and paved the way for the application of the more recently developed gene editing methods. The increasingly efficient and more recently developed gene editing methods, in particular those based on the CRISPR/Cas9 system and previous conceptually similar techniques, are already contributing to additional gene function discovery using reverse genetics and related approaches. However, gene editing methods are only possible due to the increasing availability of in vitro culture, transfection, and genome sequencing and analysis techniques. We envisage that rapid progress in the development of novel gene editing techniques applied to apicomplexan parasites of

Acanthocephala Larvae parasitizing Ameiva ameiva ameiva (Linnaeus, 1758) (Squamata: Teiidae)

OpenAIRE

Lilian Cristina Macedo; Francisco Tiago de Vasconcelos Melo; Teresa Cristina Sauer Ávila-Pires; Elane Guerreiro Giese; Jeannie Nascimento dos Santos

2016-01-01

Abstract Knowledge concerning the taxonomy and biology of species of Acanthocephala, helminth parasites of the helminth species of the phylum Acanthocephala, parasites of lizards in Brazilian Amazonia, is still insufficient, but reports of Acanthocephala in reptiles are becoming increasingly common in the literature. Cystacanth-stage Acanthocephalan larvae have been found in the visceral peritoneum during necropsy of Ameiva ameiva ameivalizards from the “Osvaldo Rodrigues da Cunha” Herpetolog...

The in vitro anthelmintic effects of plumbagin on newly excysted and 4-weeks-old juvenile parasites of Fasciola gigantica.

Science.gov (United States)

Lorsuwannarat, Natcha; Piedrafita, David; Chantree, Pathanin; Sansri, Veerawat; Songkoomkrong, Sineenart; Bantuchai, Sirasate; Sangpairot, Kant; Kueakhai, Pornanan; Changklungmoa, Narin; Chaichanasak, Pannigan; Chansela, Piyachat; Sobhon, Prasert

2014-01-01

The effect of plumbagin (PB, 5-hydroxy-2-methyl-1,4-naphthoquinone) against newly excysted juveniles (NEJs) and 4-weeks-old immature parasites of Fasciola gigantica were compared with triclabendazole (TCZ). The anthelmintic efficacy of 1, 10 and 100μg/ml of PB or TCZ following incubation in vitro for 1-24h was compared using a combination of relative motility (RM), survival index (SI) and larval migration inhibition (LMI) assays for parasite viability. The RM and SI values of the PB-treated group decreased at a more rapid rate than the TCZ-treated group. For NEJs, the decreased RM values were first observed at 1h incubation with 1μg/ml PB, and 90% of flukes were killed at 24h. In contrast, in TCZ-treated groups a 10-fold higher concentration of TCZ (10μg/ml) resulted in only 9% dead parasites after 24h incubation. In 4-weeks-old juvenile parasites, PB reduced the RM value at 10μg/ml with 100% of flukes dead after 3h, while TCZ decreased RM values at the concentration of 100μg/ml but with only 5% of flukes killed at 24h. NEJs treated with PB exhibited 88%, 99% and 100% of LMIs at the concentrations of 1, 10 and 100μg/ml, respectively. NEJs incubated with TCZ have an LMI of only 32% at the highest concentration of 100μg/ml. Similarly PB had a significantly greater killing of immature 4weeks juvenile stages than TCZ at all concentrations; however, 4-weeks-old juvenile parasites were more resistant to killing by PB or TCZ at all concentrations when compared to NEJs. Further studies were carried out to investigate the alterations of the parasite tegument by scanning electron microscope (SEM). PB caused similar tegumental alterations in 4-weeks-old juveniles as those observed in TCZ treatment but with greater damage at comparative time points, comprising of swelling, blebbing and rupture of the tegument, loss of spines, and eventual erosion, lesion and desquamation of the total tegument. These data indicate that PB had a greater fasciolicidal effect against

Consequences of Food Restriction for Immune Defense, Parasite Infection, and Fitness in Monarch Butterflies.

Science.gov (United States)

McKay, Alexa Fritzsche; Ezenwa, Vanessa O; Altizer, Sonia

2016-01-01

Organisms have a finite pool of resources to allocate toward multiple competing needs, such as development, reproduction, and enemy defense. Abundant resources can support investment in multiple traits simultaneously, but limited resources might promote trade-offs between fitness-related traits and immune defenses. We asked how food restriction at both larval and adult life stages of the monarch butterfly (Danaus plexippus) affected measures of immunity, fitness, and immune-fitness interactions. We experimentally infected a subset of monarchs with a specialist protozoan parasite to determine whether parasitism further affected these relationships and whether food restriction influenced the outcome of infection. Larval food restriction reduced monarch fitness measures both within the same life stage (e.g., pupal mass) as well as later in life (e.g., adult lifespan); adult food restriction further reduced adult lifespan. Larval food restriction lowered both hemocyte concentration and phenoloxidase activity at the larval stage, and the effects of larval food restriction on phenoloxidase activity persisted when immunity was sampled at the adult stage. Adult food restriction reduced only adult phenoloxidase activity but not hemocyte concentration. Parasite spore load decreased with one measure of larval immunity, but food restriction did not increase the probability of parasite infection. Across monarchs, we found a negative relationship between larval hemocyte concentration and pupal mass, and a trade-off between adult hemocyte concentration and adult life span was evident in parasitized female monarchs. Adult life span increased with phenoloxidase activity in some subsets of monarchs. Our results emphasize that food restriction can alter fitness and immunity across multiple life stages. Understanding the consequences of resource limitation for immune defense is therefore important for predicting how increasing constraints on wildlife resources will affect fitness and

Polydnaviruses of Parasitic Wasps: Domestication of Viruses To Act as Gene Delivery Vectors

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Michael R. Strand

2012-01-01

Full Text Available Symbiosis is a common phenomenon in which associated organisms can cooperate in ways that increase their ability to survive, reproduce, or utilize hostile environments. Here, we discuss polydnavirus symbionts of parasitic wasps. These viruses are novel in two ways: (1 they have become non-autonomous domesticated entities that cannot replicate outside of wasps; and (2 they function as a delivery vector of genes that ensure successful parasitism of host insects that wasps parasitize. In this review we discuss how these novelties may have arisen, which genes are potentially involved, and what the consequences have been for genome evolution.

A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery

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Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De-Sen

2016-01-01

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment. PMID:27008710

A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery.

Science.gov (United States)

Peng, Jian-Hong; Fang, Yu-Jing; Li, Cai-Xia; Ou, Qing-Jian; Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De Sen

2016-04-19

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.

Survival prognostic value of morphological and metabolic variables in patients with stage I and II non-small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Domachevsky, L. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Beilinson Hospital, Petah Tikva (Israel); Groshar, D.; Bernstine, H. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Galili, R. [Lady Davis-Carmel Medical Center, Department of Cardiothoracic Surgery, Haifa (Israel); Saute, M. [Rabin Medical Center, Department of Cardiothoracic Surgery, Petah Tiqva (Israel)

2015-11-15

The prognosis of patients with non-small cell lung cancer (NSCLC) is important, as patients with resectable disease and poor prognostic variables might benefit from neoadjuvant therapy. The goal of this study is to evaluate SUVmax, SUVmax ratio, CT volume (CTvol), metabolic tumour volume (MTV) and total lesion glycolisis (TLG) as survival prognostic markers. In addition, we defined two variables; MTV x SUVmax (MTVmax) and CTvol x SUVmax (CTvolmax) and assessed whether they can be used as prognostic markers. Patients with stage I-II NSCLC who underwent 18 F FDG PET/CT and surgery were evaluated. Cox proportional-hazard model was used to determine the association between variables and survival. Similar analysis was performed in cases with no lymph node (LN) involvement. One hundred and eighty-one patients were included (at the end of the study, 140 patients were alive). SUVmax with a cut-off value of 8.2 was significant survival prognostic factor regardless of LN involvement (P = 0.012). In cases with no LN involvement, SUVmax and CTvol (≥7.1 ml) were significant survival prognostic factors with P = 0.004 and 0.03, respectively. SUVmax may be a useful prognostic variable in stage I-II NSCLC while morphologic tumour volume might be useful in cases with no lymph node involvement. (orig.)

A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer

OpenAIRE

BENNETT, KATHLEEN

2013-01-01

PUBLISHED Background: Preclinical evidence suggests a beneficial effect of metformin in colorectal cancer. This study aimed to investigate associations between metformin exposure and colorectal cancer–specific survival using population-level data. Methods: Adult patients with stage I–III colorectal cancer diagnosed from 2001 to 2006 were identified from the National Cancer Registry Ireland. Use of metformin and other antidiabetic medications was determined from a linked national prescr...

Classical and anaplastic seminoma: Difference in survival

International Nuclear Information System (INIS)

Bobba, V.S.; Mittal, B.B.; Hoover, S.V.; Kepka, A.

1987-01-01

The authors undertook a retrospective study of seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 66 patients, of whom 47 were stage I and 19 were stage II. The anaplastic group consisted of 21 patients, of whom 11 were stage I, nine were stage II, and one was stage III. The median follow-up was 66 months. The five-year crude survival rate for the entire group was 92%, for classical 96%, and for anaplastic 78% (P<.005). Similarly, there was a significant difference (P<.005) in actuarial relapse-free survival at 5 years between classical and anaplastic seminoma. For classical stage I, the relapse-free actuarial 5-year survival rate was 96; for classical stage II, 84%. For anaplastic stage I the relapse-free actuarial 5-year survival rate was 82%, and for stage II 75%. Six patients in the classical group (9%) failed treatment. In the anaplastic group, five patients or 24 failed treatment. Therefore, the authors' data suggest a difference in survival and failure rate between classical and anaplastic seminoma. Extratesticular seminoma with anaplastic histology has an even worse prognosis

Macrodinychus mites as parasitoids of invasive ants: an overlooked parasitic association.

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Lachaud, Jean-Paul; Klompen, Hans; Pérez-Lachaud, Gabriela

2016-07-21

Mites are frequent ant symbionts, yet the exact nature of their interactions with their hosts is poorly known. Generally, myrmecophilous mites show adaptations for dispersal through phoresis, but species that lack such an adaptation may have evolved unusual specialized relationships with their hosts. The immature stages of Macrodinychus multispinosus develop as ectoparasitoids of pupae of the invasive ant Paratrechina longicornis. Feeding stages show regressed locomotor appendages. These mites complete their development on a single host, sucking all of its body content and therefore killing it. Locally high proportions of parasitized host pupae suggest that M. multispinosus could serve as a biological control agent. This is the ninth species of Macrodinychus reported as ant parasite, and the third known as parasitoid of invasive ants, confirming a unique habit in the evolution of mite feeding strategies and suggesting that the entire genus might be parasitic on ants. Several mites' characteristics, such as their protective morphology, possible viviparity, lack of a specialized stage for phoretic dispersal, and low host specificity, combined with both the general low aggressiveness of invasive P. longicornis towards other ants and its possible susceptibility to generalist ectoparasites would account for the host shift in native macrodinychid mites.

Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3

Directory of Open Access Journals (Sweden)

Spiro David

2009-06-01

Full Text Available Abstract Background Filarial nematode parasites cause serious diseases such as elephantiasis and river blindness in humans, and heartworm infections in dogs. Third stage filarial larvae (L3 are a critical stage in the life cycle of filarial parasites, because this is the stage that is transmitted by arthropod vectors to initiate infections in mammals. Improved understanding of molecular mechanisms associated with this transition may provide important leads for development of new therapies and vaccines to prevent filarial infections. This study explores changes in gene expression associated with the transition of Brugia malayi third stage larvae (BmL3 from mosquitoes into mammalian hosts and how these changes are affected by radiation. Radiation effects are especially interesting because irradiated L3 induce partial immunity to filarial infections. The underlying molecular mechanisms responsible for the efficacy of such vaccines are unkown. Results Expression profiles were obtained using a new filarial microarray with 18, 104 64-mer elements. 771 genes were identified as differentially expressed in two-way comparative analyses of the three L3 types. 353 genes were up-regulated in mosquito L3 (L3i relative to cultured L3 (L3c. These genes are important for establishment of filarial infections in mammalian hosts. Other genes were up-regulated in L3c relative to L3i (234 or irradiated L3 (L3ir (22. These culture-induced transcripts include key molecules required for growth and development. 165 genes were up-regulated in L3ir relative to L3c; these genes encode highly immunogenic proteins and proteins involved in radiation repair. L3ir and L3i have similar transcription profiles for genes that encode highly immunogenic proteins, antioxidants and cuticle components. Conclusion Changes in gene expression that normally occur during culture under conditions that support L3 development and molting are prevented or delayed by radiation. This may explain

Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

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Zheng, Xiangpeng; Schipper, Matthew; Kidwell, Kelley; Lin, Jules; Reddy, Rishindra; Ren, Yanping; Chang, Andrew; Lv, Fanzhen; Orringer, Mark; Spring Kong, Feng-Ming

2014-01-01

Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery

Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

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Zheng, Xiangpeng [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Schipper, Matthew [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Kidwell, Kelley [Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Lin, Jules; Reddy, Rishindra [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Ren, Yanping [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Chang, Andrew [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Lv, Fanzhen [Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai (China); Orringer, Mark [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Spring Kong, Feng-Ming, E-mail: Fkong@gru.edu [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States)

2014-11-01

Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values and small sample sizes.

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Moustakas, Aristides; Evans, Matthew R

2015-02-28

Plant survival is a key factor in forest dynamics and survival probabilities often vary across life stages. Studies specifically aimed at assessing tree survival are unusual and so data initially designed for other purposes often need to be used; such data are more likely to contain errors than data collected for this specific purpose. We investigate the survival rates of ten tree species in a dataset designed to monitor growth rates. As some individuals were not included in the census at some time points we use capture-mark-recapture methods both to allow us to account for missing individuals, and to estimate relocation probabilities. Growth rates, size, and light availability were included as covariates in the model predicting survival rates. The study demonstrates that tree mortality is best described as constant between years and size-dependent at early life stages and size independent at later life stages for most species of UK hardwood. We have demonstrated that even with a twenty-year dataset it is possible to discern variability both between individuals and between species. Our work illustrates the potential utility of the method applied here for calculating plant population dynamics parameters in time replicated datasets with small sample sizes and missing individuals without any loss of sample size, and including explanatory covariates.

Floral Volatiles in Parasitic Plants of the Orobanchaceae. Ecological and Taxonomic Implications

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Peter eTóth

2016-03-01

Full Text Available The holoparasitic broomrapes, Orobanche spp. and Phelipanche spp. (Orobanchaceae, are root parasites that completely depend on a host plant for survival and reproduction. There is considerable controversy on the taxonomy of this biologically and agronomically important family. Flowers of over 25 parasitic Orobanchaceae and a number of close, parasitic and non-parasitic, relatives emitted a complex blend of volatile organic compounds (VOCs, consisting of over 130 VOCs per species. Floral VOC blend-based phylogeny supported the known taxonomy in internal taxonomic grouping of genus and eliminated the uncertainty in some taxonomical groups. Moreover, phylogenetic analysis suggested separation of the broomrapes into two main groups parasitizing annual and perennial hosts, and for the annual hosts, into weedy and non-weedy broomrapes. We conclude that floral VOCs are a significant tool in species identification and possibly even in defining new species and can help to improve controversial taxonomy in the Orobanchaceae.

Asteraceae Pollen Provisions Protect Osmia Mason Bees (Hymenoptera: Megachilidae) from Brood Parasitism.

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Spear, Dakota M; Silverman, Sarah; Forrest, Jessica R K

2016-06-01

Many specialist herbivores eat foods that are apparently low quality. The compensatory benefits of a poor diet may include protection from natural enemies. Several bee lineages specialize on pollen of the plant family Asteraceae, which is known to be a poor-quality food. Here we tested the hypothesis that specialization on Asteraceae pollen protects bees from parasitism. We compared rates of brood parasitism by Sapyga wasps on Asteraceae-specialist, Fabeae-specialist, and other species of Osmia bees in the field over several years and sites and found that Asteraceae-specialist species were parasitized significantly less frequently than other species. We then tested the effect of Asteraceae pollen on parasites by raising Sapyga larvae on three pollen mixtures: Asteraceae, Fabeae, and generalist (a mix of primarily non-Asteraceae pollens). Survival of parasite larvae was significantly reduced on Asteraceae provisions. Our results suggest that specialization on low-quality pollen may evolve because it helps protect bees from natural enemies.

Environmentally transmitted parasites: Host-jumping in a heterogeneous environment.

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Caraco, Thomas; Cizauskas, Carrie A; Wang, Ing-Nang

2016-05-21

Groups of chronically infected reservoir-hosts contaminate resource patches by shedding a parasite׳s free-living stage. Novel-host groups visit the same patches, where they are exposed to infection. We treat arrival at patches, levels of parasite deposition, and infection of the novel host as stochastic processes, and derive the expected time elapsing until a host-jump (initial infection of a novel host) occurs. At stationarity, mean parasite densities are independent of reservoir-host group size. But within-patch parasite-density variances increase with reservoir group size. The probability of infecting a novel host declines with parasite-density variance; consequently larger reservoir groups extend the mean waiting time for host-jumping. Larger novel-host groups increase the probability of a host-jump during any single patch visit, but also reduce the total number of visits per unit time. Interaction of these effects implies that the waiting time for the first infection increases with the novel-host group size. If the reservoir-host uses resource patches in any non-uniform manner, reduced spatial overlap between host species increases the waiting time for host-jumping. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differences in crenate broomrape parasitism dynamics on three legume crops using a thermal time model

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Alejandro Pérez-De-Luque

2016-12-01

Full Text Available Root parasitic weeds are a major limiting production factor in a number of crops, and control is difficult. Genetic resistance and chemical control lead the fight, but without unequivocal success. Models that help to describe and even predict the evolution of parasitism underground are a valuable tool for herbicide applications, and even could help in breeding programs. Legumes are heavily affected by Orobanche crenata (crenate broomrape in the Mediterranean basin. This work presents a descriptive model based on thermal time and correlating growing day-degrees (GDD with the different developmental stages of the parasite. The model was developed in three different legume crops (faba bean, grass pea and lentil attacked by crenate broomrape. The developmental stages of the parasite strongly correlated with the GDD and differences were found depending on the host crop.

Parasitism and calfhood diseases.

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Herlich, H; Douvres, F W

1977-02-01

That animals can and do acquire an effective immunity against helminth parasites has been demonstrated extensively experimentally, and the fact that domestic animals such as cattle, sheep, and horses become adults while maintaining good health in spite of constant exposure to reinfection long has suggested that immunity must be important to such survival. Although our attempts to date to vaccinate calves against helminth parasites have either failed or been unsatisfactory because of the pathosis induced by the experimental vaccines, the results are not surprising or discouraging. In contrast to the long history of immunization research on bacterial and viral diseases, only within a relatively short time have serious efforts been directed at exploiting hostal immunity for prevention and control of helminthic diseases. Unlike the comparatively simple structures of viruses and bacteria, helminths are complex multicellular animals with vast arrays of antigens and complicated physiological and immunological interactions with their hosts. Much more fundamental information on helminth-bovine interactions, on helminth antigens, and on cattle antibody systems must be developed before progress on control of cattle helminths by vaccination can be meaningful.

Stable-isotope analysis: a neglected tool for placing parasites in food webs.

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Sabadel, A J M; Stumbo, A D; MacLeod, C D

2018-02-28

Parasites are often overlooked in the construction of food webs, despite their ubiquitous presence in almost every type of ecosystem. Researchers who do recognize their importance often struggle to include parasites using classical food-web theory, mainly due to the parasites' multiple hosts and life stages. A novel approach using compound-specific stable-isotope analysis promises to provide considerable insight into the energetic exchanges of parasite and host, which may solve some of the issues inherent in incorporating parasites using a classical approach. Understanding the role of parasites within food webs, and tracing the associated biomass transfers, are crucial to constructing new models that will expand our knowledge of food webs. This mini-review focuses on stable-isotope studies published in the past decade, and introduces compound-specific stable-isotope analysis as a powerful, but underutilized, newly developed tool that may answer many unresolved questions regarding the role of parasites in food webs.

Primary colectomy in patients with stage IV colon cancer and unresectable distant metastases improves overall survival: results of a multicentric study.

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Karoui, Mehdi; Roudot-Thoraval, Françoise; Mesli, Farida; Mitry, Emmanuel; Aparicio, Thomas; Des Guetz, Gaetan; DesGuetz, Gaetan; Louvet, Christophe; Landi, Bruno; Tiret, Emmanuel; Sobhani, Iradj

2011-08-01

Whether patients with stage IV colon cancer and unresectable distant metastases should be managed by primary colectomy followed by chemotherapy or immediate chemotherapy without resection of the primary tumor is still controversial. This study aimed to evaluate predictive factors associated with survival in patients with stage IV colon cancer and unresectable distant metastases. This large retrospective multicentric study included 6 academic hospitals. This study was conducted at 6 Paris University Hospitals (Assistance Publique-Hôpitaux de Paris; Saint Antoine, Henri Mondor, Ambroise Paré, Hôpital Europeen Gorges Pompidou, Bichat, and Avicenne). Between 1998 and 2007, 208 patients with good performance status and stage IV colon cancer with unresectable distant metastases received chemotherapy, either as initial management or after primary tumor resection. Survival was estimated by use of the Kaplan-Meier method. Factors associated with survival were tested by means of a log-rank test. Results were expressed as median values with 95% confidence intervals. Factors independently related to survival were tested using a Cox regression model adjusted for a propensity score. Of the 208 patients, 85 underwent colectomy before chemotherapy, whereas 123 were treated with use of primary chemotherapy with or without biotherapy. At univariate analysis, the following factors were significantly associated with survival: primary colectomy (P = .031), secondary curative surgery (P < .001), well-differentiated primary tumor (P < .001), exclusive liver metastases (P < .027), absence of need for colonic stent (P = .009), and addition of antiangiogenic (P = .001) or anti-epidermal growth factor receptor (P = .013) drugs to chemotherapy. After Cox multivariate analysis and after adjusting for the propensity score, all of these factors, with the exception of two, colonic stent and anti-epidermal growth factor receptor drug, were found to be independently associated with overall

Determinants of morbidity and survival after elective non-curative resection of stage IV colon and rectal cancer.

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Kleespies, Axel; Füessl, Kathrin E; Seeliger, Hendrik; Eichhorn, Martin E; Müller, Mario H; Rentsch, Markus; Thasler, Wolfgang E; Angele, Martin K; Kreis, Martin E; Jauch, Karl-Walter

2009-09-01

The benefit of elective primary tumor resection for non-curable stage IV colorectal cancer (CRC) remains largely undefined. We wanted to identify risk factors for postoperative complications and short survival. Using a prospective database, we analyzed potential risk factors in 233 patients, who were electively operated for non-curable stage IV CRC between 1996 and 2002. Patients with recurrent tumors, resectable metastases, emergency operations, and non-resective surgery were excluded. Risk factors for increased postoperative morbidity and limited postoperative survival were identified by multivariate analyses. Patients with colon cancer (CC = 156) and rectal cancer (RC = 77) were comparable with regard to age, sex, comorbidity, American Society of Anesthesiologists score, carcinoembryonic antigen levels, hepatic spread, tumor grade, resection margins, 30-day mortality (CC 5.1%, RC 3.9%) and postoperative chemotherapy. pT4 tumors, carcinomatosis, and non-anatomical resections were more common in colon cancer patients, whereas enterostomies (CC 1.3%, RC 67.5%, p 50%, and comorbidity >1 organ. Prognostic factors for limited postoperative survival were hepatic tumor load >50%, pT4 tumors, lymphatic spread, R1-2 resection, and lack of chemotherapy. Palliative resection is associated with a particularly unfavorable outcome in rectal cancer patients presenting with a locally advanced tumor (pT4, expected R2 resection) or an extensive comorbidity, and in all CRC patients who show a hepatic tumor load >50%. For such patients, surgery might be contraindicated unless the tumor is immediately life-threatening.

Cellulose filtration of blood from malaria patients for improving ex vivo growth of Plasmodium falciparum parasites

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Mkumbaye, Sixbert I; Minja, Daniel T R; Jespersen, Jakob S

2017-01-01

faster than non-filtered parasites seemingly due to a higher development ratio of ring stage parasites progressing into the late stages. Cellulose filtration had no apparent effect on clonality or var gene expression; however, evident differences were observed after only 4 days of culture in both...

Exploring the host parasitism of the migratory plant-parasitic nematode Ditylenchus destuctor by expressed sequence tags analysis.

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Huan Peng

Full Text Available The potato rot nematode, Ditylenchus destructor, is a very destructive nematode pest on many agriculturally important crops worldwide, but the molecular characterization of its parasitism of plant has been limited. The effectors involved in nematode parasitism of plant for several sedentary endo-parasitic nematodes such as Heterodera glycines, Globodera rostochiensis and Meloidogyne incognita have been identified and extensively studied over the past two decades. Ditylenchus destructor, as a migratory plant parasitic nematode, has different feeding behavior, life cycle and host response. Comparing the transcriptome and parasitome among different types of plant-parasitic nematodes is the way to understand more fully the parasitic mechanism of plant nematodes. We undertook the approach of sequencing expressed sequence tags (ESTs derived from a mixed stage cDNA library of D. destructor. This is the first study of D. destructor ESTs. A total of 9800 ESTs were grouped into 5008 clusters including 3606 singletons and 1402 multi-member contigs, representing a catalog of D. destructor genes. Implementing a bioinformatics' workflow, we found 1391 clusters have no match in the available gene database; 31 clusters only have similarities to genes identified from D. africanus, the most closely related species to D. destructor; 1991 clusters were annotated using Gene Ontology (GO; 1550 clusters were assigned enzyme commission (EC numbers; and 1211 clusters were mapped to 181 KEGG biochemical pathways. 22 ESTs had similarities to reported nematode effectors. Interestedly, most of the effectors identified in this study are involved in host cell wall degradation or modification, such as 1,4-beta-glucanse, 1,3-beta-glucanse, pectate lyase, chitinases and expansin, or host defense suppression such as calreticulin, annexin and venom allergen-like protein. This result implies that the migratory plant-parasitic nematode D. destructor secrets similar effectors to

Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases.

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Hussain, Tahir; Yogavel, Manickam; Sharma, Amit

2015-04-01

Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA synthetases (PfMRS), termed PfMRS(cyt) and PfMRS(api). Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRS(cyt)) or proteobacteria/primitive bacteria (PfMRS(api)). We show that PfMRS(cyt) localizes in parasite cytoplasm, while PfMRS(api) localizes to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS inhibitors, REP3123 and REP8839, hampered Plasmodium growth very effectively in the early and late stages of parasite development. Small-molecule drug-like libraries were screened against modeled PfMRS structures, and several "hit" compounds showed significant effects on parasite growth. We then tested the effects of the hit compounds on protein translation by labeling nascent proteins with (35)S-labeled cysteine and methionine. Three of the tested compounds reduced protein synthesis and also blocked parasite growth progression from the ring stage to the trophozoite stage. Drug docking studies suggested distinct modes of binding for the three compounds, compared with the enzyme product methionyl adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds that can be explored for development as antimalarial drugs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The influence of the level of lamina propria invasion and the prevalence of p53 nuclear accumulation on survival in stage T1 transitional cell bladder cancer

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Hermann, G G; Horn, T; Steven, K

1998-01-01

PURPOSE: We assessed the influence of the level of lamina propria invasion and the prevalence of p53 nuclear immunoreactivity on the survival of patients with stage T1 transitional cell bladder cancer. MATERIALS AND METHODS: All patients presenting with stage T1 bladder cancer were prospectively...... and routinely grouped according to the level of lamina propria invasion. Invasion of the tumor stalk was defined as stage T1a, invasion of the lamina propria proper superficial to the level of muscularis mucosa as stage T1b and into or deeper than the muscularis mucosa as stage T1c. The p53 nuclear...... related to age, level of lamina propria invasion and presence of p53 nuclear accumulation. For this subpopulation overall survival was 67%, and 79% for stage T1a, 70% for stage T1b and 57% for stage T1c (p

The neurotropic parasite Toxoplasma gondii increases dopamine metabolism

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The common parasite Toxoplasma gondii induces behavioral alterations in its hosts including phenotypes increasing the likelihood of its transmission in rodents and reports of psychobehavioral alterations in humans. We have found that elevated levels of dopamine are associated with the encysted stage...

High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

DEFF Research Database (Denmark)

Nielsen, Boye Schnack; Jørgensen, Stine; Fog, Jacob Ulrik

2011-01-01

Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust...... in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The mi...... relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation...

Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors

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Nir Qvit

2016-04-01

Full Text Available Parasitic diseases cause ∼500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase and TRACK (Trypanosoma receptor for activated C-kinase. We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase, may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs. Keywords: Chagas disease, Leishmaniasis, Peptide, LACK, TRACK, Scaffold protein

Expression of Plasmodium vivax crt-o Is Related to Parasite Stage but Not Ex Vivo Chloroquine Susceptibility.

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Pava, Zuleima; Handayuni, Irene; Wirjanata, Grennady; To, Sheren; Trianty, Leily; Noviyanti, Rintis; Poespoprodjo, Jeanne Rini; Auburn, Sarah; Price, Ric N; Marfurt, Jutta

2016-01-01

Chloroquine (CQ)-resistant Plasmodium vivax is present in most countries where P. vivax infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of P. vivax crt-o (pvcrt-o) has been correlated with in vivo CQ resistance in an area with low-grade resistance. We assessed pvcrt-o expression in isolates from Papua (Indonesia), where P. vivax is highly CQ resistant. Ex vivo drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of pvcrt-o were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in pvcrt-o expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the P. vivax β-tubulin gene and from 0.01 to 24 relative to that seen with the P. vivax aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5; P determinant of ex vivo drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and P. vivax drug resistance. Copyright © 2015 Pava et al.

A Cas9 transgenic Plasmodium yoelii parasite for efficient gene editing.

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Qian, Pengge; Wang, Xu; Yang, Zhenke; Li, Zhenkui; Gao, Han; Su, Xin-Zhuan; Cui, Huiting; Yuan, Jing

2018-06-01

The RNA-guided endonuclease Cas9 has applied as an efficient gene-editing method in malaria parasite Plasmodium. However, the size (4.2 kb) of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for genome editing in the parasites only introduced with cas9 plasmid. To establish the endogenous and constitutive expression of Cas9 protein in the rodent malaria parasite P. yoelii, we replaced the coding region of an endogenous gene sera1 with the intact SpCas9 coding sequence using the CRISPR/Cas9-mediated genome editing method, generating the cas9-knockin parasite (PyCas9ki) of the rodent malaria parasite P. yoelii. The resulted PyCas9ki parasite displays normal progression during the whole life cycle and possesses the Cas9 protein expression in asexual blood stage. By introducing the plasmid (pYCs) containing only sgRNA and homologous template elements, we successfully achieved both deletion and tagging modifications for different endogenous genes in the genome of PyCas9ki parasite. This cas9-knockin PyCas9ki parasite provides a new platform facilitating gene functions study in the rodent malaria parasite P. yoelii. Copyright © 2018 Elsevier B.V. All rights reserved.