bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective inability of spleen antigen presenting cells from Leishmania donovani infected hamsters to mediate specific T cell proliferation to parasite antigens
Authors: RODRIGUES VIRMONDES , DA SILVA JOAO SANTANA , CAMPOS‐NETO ANTONIO
Published: October 2007

Summary Golden hamsters (Mesocricetus auratus) infected with Leishmania donovani develop a disease similar to human kala‐azar. There is conspicuous hypergammaglobulinaemia and their T cells do not respond to stimulation by parasite antigens. The impairment of the cellular immune response seems to be restricted to parasite antigens since infected animals are able to develop a T cell response to the mitogen Concanavalin A (Con‐A) and, after sensitization, to the antigens keyhole limpet haemocyanin (KLH) and human serum albumin (DNP‐HSA). In the present investigations we studied the role played by infected macrophages in the development of the cellular unresponsiveness present in visceral leishmaniasis. Adherent spleen cells from infected hamsters were unable to present L. donovani antigens to antigen specific T cells, however they were able to present KLH. Conversely. T cells from infected animals did not respond to parasite antigens even when these antigens were presented by normal syngeneic macrophages. Interestingly, lymphocytes from inguinal lymph nodes of infected animals sensitized in their foot pad with parasite antigens proliferated well when stimulated in vitro with L. donovani antigens. These results suggest that the defect in the cellular immune response of the L. donovani infected hamsters is a consequence of a selective inability of their antigen presenting cells to process and present parasite antigens to T cells.
On the interaction between macrophages and developmental stages of Schistosoma mansoni: effect of muramyl tripeptide phosphatidyl ethanolamine (MTP‐PE) treatment on mice survival and the generation of schistosomulicidal macrophages
Authors: SEGER M. , GOLD D. , LENGY J. , PAULI H. , KEISARI Y.
Published: October 2007

Summary Schistosomiasis is a chronic disease afflicting hundreds of millions of people throughout the world against which there is as yet no effective vaccine. In the present study we tested the effect of the immunomodulator muramyl tripeptide phosphatidyl ethanolamine (MTP‐PE) on the survival of Schistosoma mansoni‐infected mice and on the induction in them of schistosomulicidal macrophages. Mice exposed to 80 cercariae each and then treated with MTP‐PE showed prolonged survival following either single or repeat infection. The treatment with MTP‐PE, when initiated 70 days post the schistosome infection, diminished significantly the mortality of infected mice over an observed period of 110 days. In terms of treatment efficacy there was no evident difference between the intravenous and intraperitoneal mode of administration of the drug. MTP‐PE treatment significantly reduced granuloma size and markedly diminished liver damage as judged by the lower levels of alkaline phosphatase in the serum. Such treatment exerted no significant effect on the spleen or liver weight in infected mice nor on the worm burden resulting from either a single or double infection. In infected and non‐treated mice, schistosomulicidal macrophages appeared after 8–10 weeks of infection. In infected mice treated with MTP‐PE there was an accelerated appearance of such macrophages and these exhibited a greater cidal effect on the schistosomula. These immunostimulatory and life‐prolonging effects of MTP‐PE on S. mansoni‐infected mice might indicate an effect of this reagent on cells involved in the granulomatous process.
Modulation of cytokine production and response phenotypes in murine trichuriasis
Authors: ELSE K.J. , HÜLTNER L. , GRENCIS R.K.
Published: October 2007

Summary BALB/K mice are usually resistant to infection with the intestinal nematode parasite Trichuris muris and exhibit a Th2 dominated (IL‐5, IL‐9) response. Conversely in B10.BR mice, which are unable to expel T. muris, Thl type (IFN‐7 producing) cells predominate. We have manipulated the course of infection in these two strains of mice such that the period of host‐parasite contact is extended in the former and curtailed in the latter. Extension of host‐parasite contact in BALB/K mice beyond normal (day 21) resulted in the modulation of cytokines produced by in vitro concanavalin A (Con‐A) stimulated MLNC away from IL‐5 and IL‐9 (Th2‐type cytokines) in favour of the Th1‐type cytokine IFN‐γ. Curtailment of host parasite contact in B10.BR mice to less that 21 days resulted in elevated production of IL‐5 and IL‐9 by MLNC in the absence of elevated IFN‐γ levels. Thus modulation of expulsion phenotype also modulates cytokine production by T‐cells in the MLN draining the site of infection, with a Th2 response being associated with resistance and a Th1 type response with the inability to expel the parasite. Mechanisms by which the modulated cytokine profiles arise are discussed.
Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization
Authors: KAMBER MARKUS , BLACKMAN MICHAEL , LIN PECK‐SUN , BROWN JAMES , WHITTLE HILTON , SCHMIDT‐ULLRICH RUPERT
Published: October 2007

Summary Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood‐stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein‐Barr virus transformed B‐cell lines (EBV‐TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B‐lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV‐TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV‐TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood‐stage parasites when using high‐resolution digitized video‐intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.
Characterization of monoclonal antibodies against eosinophil chemotactic factors from young adult worms of Angiostrongylus cantonensis
Authors: ISHIDA KAZUTO , YOSHIMURA KENTARO
Published: October 2007

Summary Two kinds of IgGl monoclonal antibodies against eosinophil chemotactic factors (ECFs) derived from Angiostrongylus cantonensis young adult worms (YA) were established. Western blot analyses demonstrated that one monoclonal antibody recognized a 16–1 kD component of YA‐whole worm extract, and the other an 85 kD component. These antibodies did not show any cross reactions against several helminth antigens, as assessed by ELISA. The chemotactic activity of YA‐whole worm extract for guinea‐pig‐eosinophils was significantly inhibited by previous incubation of the extract with these monoclonal antibodies; the monoclonal antibody recognizing the 16.1 kD component inhibited 56–61% of the ECF activity whilst the antibody recognizing the 85 kD component inhibited 20–34% of the activity. The combination of both monoclonal antibodies showed a stronger inhibitory effect (71–81%) than either antibody alone. Similar magnitudes of inhibition were noted when the chemotactic activity for human eosinophils was measured using YA‐whole worm extract preincubated with these monoclonal antibodies. Neither monoclonal antibodies inhibited the chemotactic activity of whole worm extracts of A. cantonensis first stage larvae, Metastrongylus apri adult worms, Spirometra erinacei plerocercoids and Fasciola sp. adult worms. These data suggest that the two monoclonal antibodies will be useful for the isolation and purification of ECF‐YA as well as for elucidating the possible in vivo role of ECF‐YA.
Larvicidal properties of macrophages induced by cloned murine schistosomal egg antigen‐specific CD4 positive T‐helper lymphocytes
Authors: KANAZAWA T. , HARRIS T. S. , CHIKUNGUWO S. M. , STADECKER M. J.
Published: October 2007

Summary The role of T‐helper (TH) lymphocytes in activating peritoneal macrophages (PM) to kill larvae of the helminth Schistosoma mansoni (schistosomula) was investigated with the use of egg antigen‐specific CD4 positive TH clones of both the TH1 and TH2 types. Results showed that stimulated TH1 clones, in exceedingly small numbers, or supernatants thereof, conferred on PM the ability to kill schistosomula. The molecule responsible for PM activation was found to be interferon‐γ (IFN‐γ). IFN–γ‐induced PM larvicidal activity was dependent on live cells, energy, as well as protein synthesis, and appeared to be mediated by toxic nitrogen metabolites. In contrast, egg antigen‐specific TH2 clones, or their supernatants, failed to induce PM larval killing, as they did not secrete IFN‐γ, or any equivalent macrophage activating factor. We postulate a mechanism by which egg antigen‐specific TH1 clones may be capable of playing a critical role in the resistance to schistosomal reinfection through IFN‐γ‐mediated activation of macrophage helminthotoxicity.
Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (Pf MSP1) of Plasmodium falciparum are associated with reduced malaria morbidity
Authors: RILEY E. M. , ALLEN S. J. , WHEELER J. G. , BLACKMAN M. J. , BENNETT S. , TAKACS B. , SCHONFELD H. ‐J. , HOLDER A. A. , GREENWOOD B. M.
Published: October 2007

Summary We have investigated the pattern of acquired immune responses to the major surface protein of Plasmodium falciparum merozoites (gp 190, Pf MSP1) in a malaria endemic population in West Africa. A prospective longitudinal study in 3‐ to 8‐year‐old children was conducted to examine the relationship between naturally acquired immune responses to Pf MSP1 and subsequent susceptibility to malaria infection and clinical disease. A population cross‐sectional survey was performed to investigate changes in immune response with age. The prevalence and concentration of antibodies to all regions of the molecule increased with age with the highest prevalence of antibodies being detected against regions of the molecule which are highly conserved between parasite isolates. In vitro lymphoproliferation and interferon‐gamma production in response to recombinant proteins representing polymorphic regions of the molecule also increased with age. Interestingly, proliferative responses to some regions of the molecule, including some highly conserved sequences, were highest in young children and decreased markedly with increasing age. Significant associations were observed between antibody and lymphoproliferative responses to proteins from the C terminus of the molecule and resistance to episodes of fever associated with high parasitaemia in partially immune children. In addition, high concentrations of antibodies to a conserved region close to the N terminus of Pf MSP1 were also significantly associated with protection.
The detection of autoantibodies to IgE in plasma of individuals infected with hookworm (Necator americanus) and the demonstration of a predominant IgG1 anti‐lgE autoantibody response
Authors: SHAKIB F. , PRITCHARD D. I. , WALSH E. A. , SMITH S. J. , POWELL‐RICHARDS A. , KUMAR S. , EDMONDS P.
Published: October 2007

In this study we have demonstrated significantly elevated levels of circulating IgG autoanti‐IgE antibody in hookworm infected individuals from Kebasob village on Karkar Island, Papua New Guinea. Although anti‐IgE activity was demonstrable in IgG1, IgG3 and IgG4, IgG1 was by far the most important subclass of IgG anti‐IgE in terms of frequency of detection (34/39; 87.2%) and magnitude of increase (P = 0.0000); with IgG3 (16/39; 41.0%) and IgG4 (15/39; 38.5%) antibodies being considerably less prevalent. Plasma levels of IgG1 anti‐IgE (P = 00019) and IgG3 anti‐IgE (P = 0.0034) showed significant correlations with total IgE concentrations, but not with IgE specific to excretory‐secretory worm products; thus suggesting that anti‐IgE synthesis is more related to polyclonal hyper IgE production than to antigen‐specific IgE stimulation. No correlation was seen between IgG subclass anti‐IgE levels and faecal egg counts or worm burden. Given that our data failed to show a negative or a positive correlation between anti‐IgE and the degree of infection with hookworm, it is tempting to speculate that the main role of autoanti‐IgE is to provide the host with protection against immune complex‐ and IgE‐mediated hypersensitivity reactions to parasitic antigens.
Reduced microbicidal and anti‐tumour activities of human monocytes after ingestion of Plasmodium falciparum‐infected red blood cells
Authors: FIORI P. L. , RAPPELLI P. , MIRKARIMI S. N. , GINSBURG H. , CAPPUCCINELLI P. , TURRINI F.
Published: October 2007

Oxidatively stressed red blood cells (RBC) and Plasmodium falciparum‐infected RBC (PRBC) are avidly phago‐cytosed by human peripheral monocytes. Following the ingestion of PRBC the monocytes’ ability to phagocytose PRBC and to generate aggressive oxidative compounds is severely impaired. In the present work the microbicidal and anti‐tumour capacities of monocytes fed with diamide‐treated RBC and PRBC harbouring mature (trophozoite) parasites have been investigated. The capacity of the latter, but not of the former, to phagocytose Escherichia coli and Staphylococcus aureus and to kill them, as well as ingested Candida albicans cells intracellularly, was found to be markedly impaired. Monocytes that have ingested PRBC had a significantly reduced cytostatic and cytolytic activities against a lymphoblastic tumour cell line. Monocytesfed with oxidatively stressed RBC had normal or sometimes even greater anti‐tumour activities. Monocytes that have ingested PRBC showed a reduced capability to produce superoxide following stimulation with phorbol ester. Such impairment in monocyte functions may explain the reduced antibacterial and anti‐tumour activities of monocytes in malaria patients, and could be consequential to their ability to resist bacterial infections and to provide means for the control of tumour development in those patients.
Chromatographic and antigenic properties of Echinococcus granulosus hydatid cyst‐derived glycolipids
Authors: DENNIS ROGER D. , BAUMEISTER STEFAN , IRMER GABRIELE , GASSER ROBIN B. , GEYER EGBERT
Published: October 2007

The neutral and acidic fraction glycolipids of Echinococcus granulosus metacestode tissue compartments were isolated, defined by their chromatographic and antigenic properties, and assessed as to their efficacy as antigens in the serodiagnosis of human hepatic cystic and alveolar echinococcosis, and other helminthiases. Analyses were accomplished by thin‐layer chromatography immunostaining and ELISA. The neutral glycolipid fraction's major carbohydrate epitope was the same as or very similar to that of Taenia crassiceps neutral glyco(sphingo)lipids, as represented by the ‘neogala'‐series core structure. The blood group‐active, carbohydrate epitope P1 was expressed by a number of neutral fraction glycolipid component bands. The reverse‐phase, thin‐layer chromatography‐isolated neutral fraction glycolipid component, designated Ag1, was efficient in the serological discrimination of cystic echinococcosis medium to high‐titred sera. Ag1 did not specifically discriminate low‐titred sera, i.e., other human helminthiases. The detected sialic acid residues of the acidic fraction glycolipids, on enzymatic cleavage, were identified as N‐acylneuraminic acid and terminal. The acidic fraction glycolipids exhibited the paradox of only chemically minor components being antigenic towards cystic and alveolar echinococcosis infection sera. The combined acidic fraction glycolipid components Ra and Rx were capable of serological discrimination between cystic echinococcosis, alveolar echinococcosis and other helminthiases.
Immune attrition of adult schistosomes
Authors: AGNEW A. M. , MURARE H. M. , DOENHOFF M. J.
Published: October 2007

Mouse infection models are described that demonstrate reduction in the rate of egg production in Schistosoma haematobium worms 6–10 weeks after the onset of oviposition and loss of Schistosoma bovis worms around 10 weeks after infection. Neither phenomenon has been shown in Schistosoma mansoni‐ or Schistosoma japonicum‐infected mice. The immunological basis for these anti‐adult responses was inferred by comparison with infections in T‐cell deprived mice and by transferance of the ability to reduce a S. bovis worm burden in immuno‐compromised hosts with immune serum. Vaccination with irradiation‐attenuated parasites of S. haematobium was also shown to have consequences for the adults of challenge infections of either S. haematobium or of S. bovis, but not of S. mansoni. Thus, prior vaccination resulted in an abrogation of the reduced egg production by S. haematobium and S. bovis worms and also of the adult worm elimination that occurred in non‐vaccinated S. bovis‐infected mice. These models are being used to define the targets and mechanisms involved in the attrition of adult worms of schistosomes with terminal spined eggs.
Alterations induced by Trypanosoma cruzi in activated mouse lymphocytes
Authors: LOPEZ H. MEJIA , TANNER M. K. , KIERSZENBAUM F. , SZTEIN M. B.
Published: October 2007

Although a number of immunological anomalies have been shown to occur during the acute period of Trypanosoma cruzi infection, the contribution of the parasite has not been clarified. In this work, we co‐cultured activated splenic mononuclear cells (SMC) from normal oulbred (CD1) or inbred (CBA/J) mice with purified T. cruzi trypomastigotes and studied ensuing T‐ and B‐ lymphocyte alterations. In the presence of parasites, phytohaemagglutinin‐stimulated SMC from either mouse background manifested a marked reduction in both lymphoproliferative capacity (i.e., 3H‐thymidine incorporation) and cell membrane levels of interleukin‐2 receptors (H.‐2R; determined by flow cytomet.y) relative to SMC from parasite‐free cultures. Thus, substantial proportions of activated SMC either became unable to express detectable levels of IL‐2R or expressed this receptor in significantly lower numbers than control SMC. Supernatants from T. cruzi suspensions reproduced these suppressive effects on phytohaemagglutinin‐stimulated SMC from normal or chronically infected CD1 or CBA/J mice. Similar results were obtained with SMC activated with a bacterial lipopolysaccharide. Since IL‐2R expression is required for activated lymphocytes to progress through the cell cycle and multiply to mount effective immune responses, impaired IL‐2R expression by T. cruzi provides a plausible hypothesis for the wide‐ranged immunosuppression that occurs in the infected host.
Phenotypic and functional properties of Th lines and clones recognizing larval antigens of Schistosoma mansoni
Authors: PEMBERTON R. M. , COULSON P. S. , SMYTHIES L. E. , WILSON R. A.
Published: October 2007

Five T cell clones and two lines were derived from the lymph nodes (LN) of C57BL/6 mice immunized with radiation‐attenuated lung‐stage larvae of Schistosoma mansoni. All seven clones/lines were CD4+, CD8‐ and expressed high levels of CD44 and CD45RB surface markers. After prolonged maintenance in‐vitro, with soluble antigen from 18 h schistosomula (SSP), five retained the ability to proliferate readily and release IFNg in response to conca‐navalin A (Con‐A) and to SSP and/or soluble adult worm antigen (SWAP). These Th clones/lines induced significant footpad DTH reactions when injected with SWAP, but were unable to confer protective immunity after transfer to naïve recipient mice. This result could be explained by the antigen specificity of the clones/lines, since they were not able to release IFNg when cultured in‐vitro with living lung‐stage larvae. A second possibility is that the high level of CD45RB expression, which is not seen on the surface of pulmonary CD4+ memory/effector cells isolated directly from protectively‐vaccinated mice, alters the ability of the clones/lines to release IFNg and to induce a DTH response in the lungs when they encounter antigen released from migrating schistosomula.
The inhibitory effect of ovine recombinant interferon‐gamma on intracellular replication of Toxoplasma gondii
Authors: OURA C. A. L. , INNES E. A. , WASTLING J. M. , ENTRICAN G. , PANTON W. R. M.
Published: October 2007

A model for the in vitro infection of ovine cells with Toxoplasma gondii tachyzoites has been developed and used to investigate the effect of treatment with ovine recombinant interferon‐gamma (ov.rIFNγ) on parasite replication. Treatment of both alveolar macrophages and fibroblast cells either 24 h pre‐infection or 2 h post‐infection with ov.rIFNγ inhibited replication of T. gondii and was quantified by suppression of 3H uracil uptake by the parasite. Replication of T. gondii in the fibroblast cells was significantly inhibited by treatment with 200‐300 U/ml ov.rIFNγ, whereas concentrations as low as 1 U/ml suppressed parasite replication in the alveolar macrophages.
Studies on the immunogenicity of a recombinant ookinete surface antigen Pbs21 from Plasmodium berghei expressed in Escherichia coli
Authors: MATSUOKA HIRO , PATON MICHAEL G. , BARKER GUY C. , BLANCO A. RICHARD ALEJO , SINDEN ROBERT E.
Published: October 2007

Plasmodium berghei ookinete surface antigen (Pbs21), was produced as a fusion product with maltose binding protein (MBP) in Escherichia coli and used to induce transmission‐blocking immunity in mice. Specificity of induced antibody was confirmed by Western blotting with native ookinete Pbs21, and by the indirect immunofluorescent antibody test on ookinete bloodfilms. Immunized mice were infected with P. berghei and transmission to Anopheles stephensi mosquitoes determined by both the intensity and prevalence of oocyst infections. Compared with a control group immunized with MBP alone the maximum blockade of oocyst intensity was 66% in the mice immunized with recombinant MBP‐Pbs21. Over nine experiments blockade averaged only 33%. By comparison with native Pbs21 protein, which usually induces 90% blockade, our data suggests the recombinant protein produced in this bacterial system is a less effective immunogen despite expressing epitopes recognized by known transmission‐blocking monoclonal antibodies.
Toxoplasma gondii: detection of antibodies in human saliva and serum
Authors: HAJEER A. H. , BALFOUR A. H. , MOSTRATOS ANN , CROSSE BARBARA
Published: October 2007

Saliva samples from 27 patients with a recent toxoplasma infection were tested for specific IgG, IgM and IgA antibodies to Toxoplasma gondii. Thirteen of the 27 saliva samples were positive for IgG anti‐T. gondii by direct agglutination and 8 of the 27 were positive for IgM anti‐T. gondii by an immunosorbent agglutination assay. Twenty of the 27 saliva samples were positive for IgG antibody on toxoplasma immunoblots with three major immunodominant antigens; 38, 30 and 35 kDa. IgA results on toxoplasma immunoblots were positive for all three groups tested, recently infected patients, chronically infected and seronegative adults without distinguishing between them. The 35 and 43 kDa antigens were the most frequently detected proteins. IgM in saliva gave negative or very weak reactions. None of the eight seronegative or the 17 chronically infected adults gave positive results in any of the tests performed to detect IgG or IgM in saliva. Serial saliva and serum samples from a laboratory‐infected patient were collected and tested for toxoplasma‐specific IgG, IgM and IgA. IgG in saliva was detected by 27 days post infection (p.i.) and was negative by 81 days p.i.; it detected mainly the 38 and 30 kDa antigens. IgM in saliva was detected by 11 days p.i. and was negative by 81 days p.i., with no reaction on immunoblots.
Strongyloides venezuelensis infection in Syrian golden hamster, Mesocricetus auratus, with reference to the phenotype of intestinal mucosal mast cells
Authors: SHI B. ‐B. , ISHIKAWA N. , KHAN A. I. , TSUCHIYA K. , HORII Y. , NAWA Y.
Published: October 2007

Syrian golden hamster, Mesocricetus auratus, was found to be a moderately susceptible host for the intestinal helminth, Strongyloides venezuelensis. After infection by subcutaneous inoculation with 3000 infective larvae(L3), about 20% of them became adult worms in the small intestine, and, after a stable infection up to day 20, adult worms were slowly and gradually expelled towards day 45. Before infection, mast cells in the jejunum were about 30/10 villus crypt units and over 80% of them were formalin‐resistant and berberine sulphate‐fluorescence positive. After infection with S. venezuelensis, the number of intestinal mast cells gradually increased with time and about a half of them were formalin‐sensitive and berberine sulphate fluorescence‐negative. Intraepithelial migration of mast cells was never seen before and after infection. Heterogeneity of mucosal mast cells in terms of granular proteoglycans was further confirmed by the determination of critical electrolyte concentration. In spite of the heterogeneity of proteoglycans, enzyme‐histochemical study revealed that practically all mucosal mast cells of Syrian golden hamsters were positive for chymase but negative for tryptase. Mast cells in the skin and tongue were also positive for chymase but negative for tryptase. Together with our previous study on mucosal mast cells of other rodents, phenotypic variances of mucosal mast cells seem to be closely related to the protective capacity against the genus Strongyloides.
Characterization of the recognition specificity of autoreactive, polyspecific monoclonal antibodies obtained from spleen cells of parasite‐infected BALB/c mice
Authors: SAITO SUSUMU , ROJEKITTIKHUN WICHIT , GAO PENG , YAMASHITA TAKAO , WATANABE TADASHI , SAKATO NOBUO , SENDO FUJIRO
Published: October 2007

We examined the specificity of four monoclonal antibodies (MoAbs) obtained from Schistosoma japonicum (1D, GAO3), Trypanosoma cruzi (TSLO), and Trichinella spiralis (TSY2) infected BALB/c mice. All four MoAbs reacted not only with autologous parasite antigens but also with various heterologous parasite antigens and normal tissues. The antigen recognition pattern seen on Western blots was almost identical in 1D and GAO3, and in TSLO and TSY2. Furthermore, certain bands were identical among all four MoAbs. The mechanisms responsible for these phenomena are discussed.
Possible role of nitric oxide in malarial immunosuppression
Authors: ROCKETT KIRK A. , AWBURN MELISSA M. , ROCKETT ELIZABETH J. , COWDEN WILLIAM B. , CLARK IAN A.
Published: October 2007

We have tested the hypothesis that nitric oxide may be responsible for the immunosuppression reported during malaria infections. We first showed that reactive nitrogen intermediates, which indicate nitric oxide generation, were increased in the plasma of Plasmodium vinckei‐infected mice. We next found that Concanavalin A‐induced proliferation of spleen cells from these mice was reduced compared with that observed in uninfected animals. The addition of NG‐methyl‐L‐arginine (L‐NMMA) for the duration of the cultures restored the malarial proliferative response to normal. We then tested the effect of oral L‐NMMA on the proliferative response of P. chabaudi‐infected mice to a human red blood cell lysate. The secondary response to this antigen, measured as spleen cell proliferation in vitro ten days after immunization and when there was no discernible parasitaemia, remained normal in L‐NMMA‐ treated P. chabaudi mice, but was decreased in the untreated infected mice. These results suggest a role for nitric oxide in malarial immunosuppression.
Roles for both CD+ and CD8+ T cells in protective immunity against Onchocerca lienalis microfilariae in the mouse
Authors: FOLKARD SHELLEY G. , BIANCO ALBERT E.
Published: October 2007

Mice inoculated with microfilariae of the filarial nematode Onchocerca lienalis clear their parasites from the skin over a period of 3 to 4 months and are highly resistant to a challenge infection. The adoptive transfer of spleen cells at various time points following primary and secondary infections of mice shows that exposures of 50 days or greater are required for the generation of lymphocytes capable of transferring protection to naive recipients. This adoptive transfer of protection with spleen cells from infection‐primed mice partitions with the T lymphocyte population. In contrast, the passive transfer of protection with spleen‐derived B cells, or sera taken at various time points following infection was not achieved. Moreover, there was no detectable synergistic effect when B and T cells were co‐administered to recipient animals. Depletion of CD4+ and CD8+ T cells with monoclonal antibodies shows that CD8 + T cells have some regulatory effect on parasite establishment early in primary infection, but this is later superseded by CD4+ T cell reactivity that is predominant both when primary infection microfilariae are cleared and also during resistance to reinfection. Measurement of cytokines in the sera of mice undergoing primary and secondary infections support a microfilariae‐induced Th2 activity, with high levels of IL‐5 that are sustained upon reinfection, and low levels oflFN‐γ that are negligible at the time when mice are most strongly immune.
Clethrionomys glareolus, but not Apodemus flavicollis, acquires resistance to lxodes ricinus L, the main European vector of Borrelia burgdorferi
Authors: DIZIJ ASTRID , KURTENBACH KLAUS
Published: October 2007

The European rodents Clethrionomys glareolus (bank vole) and Apodemus flavicollis (yellow‐necked‐mouse) are important hosts of the tick species Ixodes ricinus, the main European vector of Borrelia burgdorferi. We have addressed the question whether or not these tick hosts develop resistance to I. ricinus larvae. C. glareolus and A. flavicollis were exposed to 40 I. ricinus larvae for five consecutive times at two week intervals. Resistance was tested by the following parameters: percentage of ticks fully engorged, time of attachment, engorgement index, percentage of recovered ticks and proportion of larvae moulting to nymphs. Repeated infestation ofC. glareolus resulted in progressive and significant reductions in the percentage of fully engorged ticks, the time of attachment of partially engorged ticks, the scutal index of partially engorged ticks and the moulting success. In contrast, repeatedly infested A. flavicollis did not acquire resistance to larval I. ricinus. Effects of resistance in C glareolus could be partially disrupted by treatment with the immunosuppressive agent, cyclosporin A (CsA), indicating that T helper cells participate in the immune responses to tick bites. The data suggest that acquired immunity to I. ricinus larvae in C. glareolus is a density‐dependent factor regulating natural tick burdens and that it may have an impact on the transmission cycle of B. burgdorferi in Central Europe.
Strain variation limits protective activity of vaccines based on soluble Babesia canis antigens
Authors: SCHETTERS TH. , KLEUSKENS J. , SCHOLTES N. , BOS H. J.
Published: October 2007

Groups of five dogs were immunized with vaccines containing soluble parasite antigens (SPA) derived from in vitro culture of Babesis canis parasites, either obtained commercially (Pirodog®) or produced at laboratory scale. Both vaccines generated antibodies that reacted with parasitised erythrocytes (PE). Upon challenge infection with homologous parasites, protection was evident from less severe decreases of haematocrit values, and reduced morbidity. Vaccinated animals, however, were not protected against challenge infection with heterologous B. canis parasites. Recovery from challenge infection coincided with the production of antibodies against parasitized erythrocytes. The results suggest that SPA from B. canis carry strain‐specific determinants that are crucial for inducing protection in dogs against challenge infection, and explain vaccination failures in the field.
Plasmodium vivax: detection of blood parasites using fluorochrome labelled monoclonal antibodies
Authors: PEREZ HILDA A. , WIDE ALBINA , BRACHO CARMEN , la ROSA MERCEDES
Published: October 2007

A monoclonal antibody (MoAb) 2C6111 specific for Plasmodium vivax erythrocytic stages was shown to detect parasitized erythrocytes in blood samples collected in the field. This MoAb binds to the mature trophozoite, schizont and gametes of P. vivax and upon examination of 43 wild isolates no evidence of polymorphism was found. To search for P. vivax parasites in human blood a MoAb immunofluorescent test (MoAb‐IFT) was developed. The assay is based on the ability of fluorescein isothiocyanate labelled MoAb 2C6111 to combine with parasitized erythrocytes on thin blood smears. A preliminary field trial was carried out in Venezuela to determine the usefulness of MoAb‐IFT for the specific diagnosis of P. vivax malaria. Blood samples collected from malarious and non‐malarious individuals were examined both by standard microscopy of Giemsa stained thick blood smears (G‐TS) and MoAb‐IFT. The latter was specific and gave a 100% correlation with G‐TS. Sensitivity was close to that usually achieved with Giemsa stained blood films.,
Anti‐fecundity immunity induced in pigs vaccinated with recombinant Schistosoma japonicum 26kDa glutathione‐S‐transferase
Authors: LIU S.X. , SONG G.C. , XU Y.X. , YANG W. , McMANUS D.P.
Published: October 2007

We have recently reported (Liu et al. 1995) that immunization of mice with recombinant 26kDa GST (reSjc26GST) induces a pronounced anti‐fecundity effect after experimental infection with Chinese Schistosoma japonicum. A similar vaccination trial was thus carried out on pigs, important reservoirs for schistosomiasis japonica, using purified, reSjc26GST and reSjp26GST from Schistosoma japonicum with alum as adjuvant; in general, similar results were obtained with the two sources of recombinant 26 kDa GST. Some protection in terms of worm reduction, significant with males, against challenge infection was observed in vaccinated pigs. Moreover, prior to challenge, levels of specific anti‐re26GST antibodies in the vaccinated pigs were significantly higher than in non‐vaccinated pigs as determined by GST‐ELISA. The most striking feature of the vaccine trial was the significant reduction in the number of eggs, especially mature eggs, in the livers of vaccinated animals. The results indicate that immunization with recombinant Sj26GST can provide some reduction in worm burden following exposure of pigs to reinfection with S. japonicum. In addition, reSj26GST can induce an anti‐fecundity effect, thereby reducing pathology, coupled with a delay or interruption of the development of immature to mature eggs in the liver. As a consequence, vaccination with SJ26GST would also prove useful in affecting the transmission of schistosomiasis japonica.
A pilot safety and immunogenicity study of the malaria vaccine SPf66 in Gambian infants
Authors: LEACH AMANDA , DRAKELEY CHRISTOPHER J. , D'ALESSANDRO UMBERTO , FEGAN GREGORY W. , BENNETT STEPHEN , BALLOU W. RIPLEY , TARGETT GEOFFREY A.T. , GREENWOOD BRIAN M.
Published: October 2007

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 has been undertaken in 150 Gambian infants. No significant systemic side effects were recorded but modest local reactions were seen after the administration of a third 1.0 mg dose. SPf66 produced in Colombia was more immunogenic than SPf66 produced in the USA and a 1.0 mg dose of each vaccine gave higher antibody levels than a 0.5 mg dose. However, antibody levels fell rapidly after administration of the third dose of vaccine and showed little change over the following malaria transmission season. The incidence of clinical malaria was higher among children who received SPf66 than among children who received inactivated polio vaccine, the effect being most marked among children who received 1.0 mg Colombian SPf66. As the trial was not designed to measure the effect of SPf66 on morbidity from malaria, the significance of this finding is uncertain.
Study of the in vitro activation of the complement alternative pathway by Echinococcus granulosus hydatid cyst fluid
Authors: FERREIRA ANA M. , WÜRZNER REINHARD , HOBART MICHAEL J. , LACHMANN PETER J.
Published: October 2007

In the present study we have investigated the fluid phase activation of the complement (C) alternative pathway by Echinococcus granulosus sheep hydatid cyst fluid (SHCF) and its higher molecular weight fraction (SHCF‐I) by quantitating the formation of both the terminal C intermediary C5b6 complex and the terminal C complex (TCC). Our results show that in vitro C activation progresses beyond the C5 step suggesting that potentially lytic complexes may be generated in vivo. In addition, SHCF and SHCF‐I glucidic moieties are probably involved in C activation since 80% and 86% of SHCF and SHCF‐I activity respectively was destroyed by period‐ate oxidation. Furthermore, partial deglycosylation with Peptide N‐Glycosidase F of SHCF‐I which had been digested with Pronase E, released an active fraction (MW <14KDa) which bound to Soybean agglutinin, suggesting that N‐linked oligosaccharides containing α‐or β‐linked N‐acetyl galactosamine play a role in C activation by SHCF.,
Active immunization of mice with Schistosoma mansoni worm membrane antigens enhances efficacy of praziquantel
Authors: FALLON PADRAIC G. , DOENHOFF MICHAEL J.
Published: October 2007

The efficacy of praziquantel treatment was significantly enhanced (P < 0.01) in CBA/Ca mice that had been immunized prior to Schistosoma mansoni infection with a crude extract of worm membrane antigens. In Western immunoblots sera from the worm antigen‐immunized animals had a poly specific antibody response, with a 25–27 kDa antigen being reacted against with particular intensity. A molecule of similar size was also recognized by rabbit antisera raised against an antigen with esterase activity that has been previously identified as a sensitive target for drug‐antibody synergy. The increase in efficacy of subcurative doses of praziquantel in immunized animals is attributed to drug‐induced tegumental damage causing antigens to become exposed on the worm surface. Thus, specific antigens, including the 25–27kDa antigen, become accessible to circulating schistosomicidal antibodies. The role of antibodies that can synergize with praziquantel to kill schistosome worms is discussed.,
Calcium influxes and mitogen‐activated protein kinase kinase activation mediate ethylene inducing ipomoelin gene expression in sweet potato
Authors: CHEN YU‐CHI , LIN HSIN‐HUNG , JENG SHIH‐TONG
Published: October 2007

The ipomoelin gene (IPO) was identified to be a wound‐inducible gene from Ipomoea batatas, and its expression was stimulated by methyl jasmonate (MeJA) and hydrogen peroxide. IPO protein was also characterized as a defence‐related protein, and it is also a carbohydrate‐binding protein. In this study, the expression of IPO was used as a molecular probe to study the effects of Ca2+ on the signal transduction of ethylene. A confocal microscope monitored the Ca2+ within cells, and Northern blotting examined IPO expression. The presence of Ca2+ channel blocker, including diltiazem, neomycin or ruthenium red, abolished the increase of cytosolic Ca2+, and reduced the IPO expression in the cells induced by ethylene. Furthermore, both Ca2+ influxes and IPO expression stimulated by ethylene were prohibited in the presence of 10 mm ethylene glycol‐bis(2‐aminoethyl ether)‐N, N, N′, N′‐tetraacetic acid (EGTA). These results indicated that Ca2+ influxes into the cytosol induced by ethylene are from both apoplast and organelles, and are required for activating IPO expression. However, in the presence of 1 mm EGTA, ethylene can still stimulate IPO expression, but mechanical wounding failed to do it. Therefore, Ca2+ channels in the plasma membrane induced by ethylene have higher affinity to Ca2+ than that stimulated by wounding. Moreover, the addition of A23187, an ionophore, raised cytosolic Ca2+, but was unable to stimulate IPO expression. These findings showed that IPO induction did not solely depend on Ca2+, and Ca2+ elevation in cytosol is necessary but not sufficient for IPO expression. The application of PD98059, a mitogen‐activated protein kinase kinase (MAPKK) inhibitor, did not prevent Ca2+ from increasing in the cytosol induced by ethylene, but inhibited the IPO expression stimulated by staurosporine (STA), a protein kinase inhibitor. Conclusively, elevation of cytosolic Ca2+ by ethylene may stimulate protein phosphatase and MAPKK, which finally activates IPO expression.
Mycosis fungoides and Sezary syndrome against a human immunodeficiency virus‐positive background: case report
Authors: Gahongayire Françoise
Published: October 2007

Background  Mycosis fungoides (MF) and Sezary syndrome (SS) are forms of primary cutaneous T‐cell lymphoma. They are relatively rare diseases, infrequent in Europe, Asia, and Africa. In Rwanda, they remain very rare. Their etiopathogenesis has long been obscure and poorly understood. Recent studies, however, have confirmed that they are of viral origin, specifically human T‐cell lymphotropic virus type I (HTLV‐I) and human immunodeficiency virus (HIV). Their incidence is low: about three new cases per year per million inhabitants. Individuals affected are usually aged between 40 and 60 years and of male gender. The incidence of SS is less than one new case per year per million inhabitants.

Methods  A new case of MF/SS syndrome against a HIV‐positive background is described and a literature review is performed.

Results  Clinically, MF is characterized at onset by pruriginous, disseminated, erythematous, scaly plaques, localized on the skin, which gradually become infiltrative. In advanced stages, the nodular lesions can become ulcerated and Sezary cells are detected in the peripheral blood. Our male Rwandan MF/SS/HIV‐positive patient presented with pruriginous, erythematous, scaly lesions, which had developed over 4 years and were now infiltrative, together with nodular lesions of various sizes, localized on the face, scalp, and palmar and plantar regions. All of these clinical signs, the anatomopathologic examination, retroviral serology, and testing of peripheral blood confirmed the diagnosis of MF/SS against a background of immunodepression.

Conclusions  MF and SS are relatively rare cutaneous lymphomas, but have been diagnosed in Rwanda against a clinical picture of immunodepression. Their etiology seems to be viral in origin. MF and SS are difficult diseases to diagnose, with confirmation only at advanced stages. No tests exist to aid and confirm the diagnosis in the initial stages of the diseases. Further studies are urgently needed on these diseases.
Some Nigerian plants of dermatologic importance
Authors: Ajose Frances O. A.
Published: October 2007

Background According to the World Health Organization (WHO), 80% of the world's population uses medicinal plants in the treatment of diseases and, in African countries, this rate is much higher. In recent years, however, medicinal plants have represented a primary health source for the pharmaceutical industry. No less than 400 compounds derived from plants are currently used in the preparation of drugs, such as vincristine and vinblastine used in the treatment of cancer. Nigerians still depend largely on crude herbal remedies or traditional medicine. They also use wild plants for cosmetics and perfumery. Some of these herbal remedies have been observed to be effective in certain skin diseases.

Methods The data were obtained from history questionnaires completed by patients at the Dermatology Clinic, Lagos State University Teaching Hospital (LASUTH), Ikeja, Lagos, Nigeria, and from oral interviews with vendors and prescribers of herbal preparations at major markets at Lagos and Ijebu‐Ode in south‐west Nigeria, between July 2004 and July 2006. Photographs of plants were taken at private residences at Lagos, Ibadan, and Ijebu‐Ode in south‐west Nigeria. A literature search was conducted on 38 of the plants. The data are presented in tabular form.

Results Sixty‐five per cent of patients had applied some form of herbal remedy before attending our clinic. The reasons for consultation included relapses, unsustained relief, incomplete resolution, and post inflammatory hyperpigmentation. Lesions for which herbs were successfully applied included infantile eczema and seborrhoiec dermatitis, atopic eczema, impetigo, impetiginized eczema, tinea capitis, scabies, erythema multiforme, leg ulcers, localized vitiligo, and sexually transmitted diseases. Partial relief was achieved in dermatophytoses, ichthyosis, leprosy, and systemic lupus erythematosus (SLE). Some forms of alopecia, onychomycosis, and vitiligo, as well as allergic dermatoses, were not improved by herbal medicines. The preparation of the remedies was mostly by heating and boiling, infusion, and maceration. In most cases, mixtures of plants or other substances were used. The preparations were applied as poultices, ointments, baths, soaks and soaps, and oral fluids. The plants used includedAdansonia digitata,Aframomum melegueta,Aloe species,Azadirachta indica,Cassia alata,Alstonia boonei,Ficus asperifolia,Cocos nucifera,Jatropha gossypyfolia,Ocimum gratissimum,Ricinus communis. A literature search on 38 of the plants used by herbal prescribers revealed the presence of established antimicrobial agents, immune modulating agents, antioxidants, other vitamins and minerals, volatile oils and emollients, and anti‐inflammatory agents. Some of the plants may be contaminated by mycotoxins because of poor storage.

Conclusion There appears to be clinical, scientific, and pharmacologic basis for the use of herbal preparations. Nigeria needs to provide effective coordination of the practice of herbal medicine to ensure safety, standardization, and preservation of the flora.
Donor‐specific antibodies by flow single antigen beads in pediatric living donor kidney transplants: Single center experience
Authors: Roberti Isabel , Vyas Shefali , Pancoska Carol
Published: October 2007

Abstract:  Flow PRA and SAB are now routinely performed to identify HLA antibodies in the recipient sera. The presence of DSA is considered a risk factor for graft failure. However, this risk is not clearly defined. We reviewed all the pediatric recipients of living donor kidney transplants since Flow PRA and Flow SAB became routinely done at our institution. All children had negative CDC and Flow XMs. Comparison of clinical outcome was done between those with and without pretransplant DSA. Six children had positive DSA by Flow SAB. They received thymoglobulin, steroids, tacrolimus, and MMF. Five had anti‐HLA class I antibodies and one anti‐HLA class II. Only one child had an AR. Graft survival: 100% at last visit with GFR >70 mL/min/1.73 m2. A control group without DSA was used for comparison (n = 44). They received our standard protocol: basiliximab, tacrolimus, MMF, and steroids. AR rate was 9%. Both groups had similar follow‐up time, and patient and graft survival rates. In our small series, we saw excellent outcome despite the presence of DSA pretransplant. No unequivocal ideal to establish the ideal immunosuppressive regimen for this cohort of patients has been established and the long‐term outcome of these recipients has not been delineated.