Imperial College London

Emeritus ProfessorRobertSinden

Faculty of Natural SciencesDepartment of Life Sciences

Emeritus Professor of Parasite Cell Biology
 
 
 
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Contact

 

r.sinden Website

 
 
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Location

 

2.1Centre for Population BiologySilwood Park

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Summary

 

Publications

Publication Type
Year
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381 results found

FOWLER RE, SINDEN RE, PUDNEY M, 1995, INHIBITORY ACTIVITY OF THE ANTIMALARIAL ATOVAQUONE (566C80) AGAINST OOKINETES, OOCYSTS, AND SPOROZOITES OF PLASMODIUM-BERGHEI, JOURNAL OF PARASITOLOGY, Vol: 81, Pages: 452-458, ISSN: 0022-3395

Journal article

MARGOS G, KURTENBACH K, POSNETT E, BARKER GC, MATSUOKA H, PATON MG, SINDEN REet al., 1995, DEPRESSION OF THE PLASMODIUM-BERGHEI OOKINETE PROTEIN PBS21 IN A BACULOVIRUS-INSECT CELL SYSTEM PRODUCES AN EFFICIENT TRANSMISSION-BLOCKING IMMUNOGEN, PARASITE IMMUNOLOGY, Vol: 17, Pages: 167-176, ISSN: 0141-9838

Journal article

HOGH B, THOMPSON R, HETZEL C, FLECK SL, KRUSE NAA, JONES I, DGEDGE M, BARRETO J, SINDEN REet al., 1995, SPECIFIC AND NONSPECIFIC RESPONSES TO PLASMODIUM-FALCIPARUM BLOOD-STAGE PARASITES AND OBSERVATIONS ON THE GAMETOCYTEMIA IN SCHOOLCHILDREN LIVING IN A MALARIA-ENDEMIC AREA OF MOZAMBIQUE, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 52, Pages: 50-59, ISSN: 0002-9637

Journal article

THOMPSON J, SINDEN RE, 1994, IN-SITU DETECTION OF PBS21 MESSENGER-RNA DURING SEXUAL DEVELOPMENT OF PLASMODIUM-BERGHEI, MOLECULAR AND BIOCHEMICAL PARASITOLOGY, Vol: 68, Pages: 189-196, ISSN: 0166-6851

Journal article

RANAWAKA GRR, FLECK SL, BLANCO ARA, SINDEN REet al., 1994, CHARACTERIZATION OF THE MODES OF ACTION OF ANTI-PBS21 MALARIA TRANSMISSION-BLOCKING IMMUNITY - OOKINETE TO OOCYST DIFFERENTIATION IN-VIVO, PARASITOLOGY, Vol: 109, Pages: 403-411, ISSN: 0031-1820

Journal article

Ranawaka GR, Fleck SL, Blanco AR, Sinden REet al., 1994, Characterization of the modes of action of anti-Pbs21 malaria transmission-blocking immunity: ookinete to oocyst differentiation in vivo., Parasitology, Vol: 109 ( Pt 4), Pages: 403-411, ISSN: 0031-1820

The impact of immune sera, and peripheral blood cells (PBC) from mice immunized with Plasmodium berghei ookinetes; and of purified immunoglobulin or Fab fragments from anti-Pbs21 monoclonal antibody 13.1, upon establishment of oocyst infections in the mosquito was studied. Infections were initiated either from gametocyte-infected mice, or membrane feeders which contained either gametocytes or mature ookinetes. PBC from ookinete-immunized mice presented with non-immune serum failed to show any transmission-blocking activity. Anti-ookinete serum, intact anti-Pbs21 monoclonal antibody 13.1 or its Fab fragments, all inhibited oocyst formation significantly. When gametocyte-infected mice or gametocytes in membrane feeds were used, inhibition did not directly correlate with antibody concentration. In membrane feeders that contained ookinetes and antibody, concentration-dependent inhibition usually occurred. The efficacy of purified 13.1 IgG was dependent upon the ookinete concentration. The ookinete plasmalemma and cytoplasm were significantly disturbed after 12 h in bloodmeals that contained antibody 13.1, but not in the isotype controls. These changes may have caused the observed failure of the ookinete to migrate as rapidly as the controls from the destructive environment of the bloodmeal.

Journal article

BILLINGSLEY PF, MEDLEY GF, CHARLWOOD D, SINDEN REet al., 1994, RELATIONSHIP BETWEEN PREVALENCE AND INTENSITY OF PLASMODIUM-FALCIPARUM INFECTION IN NATURAL-POPULATIONS OF ANOPHELES MOSQUITOS, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 51, Pages: 260-270, ISSN: 0002-9637

Journal article

JONES IW, DENHOLM AA, LEY SV, LOVELL H, WOOD A, SINDEN REet al., 1994, SEXUAL DEVELOPMENT OF MALARIA PARASITES IS INHIBITED IN-VITRO BY THE NEEM EXTRACT AZADIRACHTIN, AND ITS SEMISYNTHETIC ANALOGS, FEMS MICROBIOLOGY LETTERS, Vol: 120, Pages: 267-273, ISSN: 0378-1097

Journal article

Ranawaka GR, Alejo-Blanco AR, Sinden RE, 1994, Characterization of the effector mechanisms of a transmission-blocking antibody upon differentiation of Plasmodium berghei gametocytes into ookinetes in vitro., Parasitology, Vol: 109 ( Pt 1), Pages: 11-17, ISSN: 0031-1820

The transmission-blocking monoclonal antibody 13.1, which recognizes the ookinete surface antigen Pbs21 of Plasmodium berghei, and an IgG2a isotype control antibody 26.37 were purified by caprylic acid and ammonium sulphate precipitation. Fab fragments were prepared by papain digestion. IgG but not Fab from antibody 13.1 reduced ookinete formation by P. berghei in culture by as much as 94% at a concentration of 100 micrograms/ml. There was little difference in antibody efficacy in the range 6.25-400 micrograms/ml in this assay. The parasite was most sensitive to antibody activity in the first 6-9 h of culture, i.e. the gamete/zygote and early retort stages. Peripheral blood leucocytes (PBL) were essential to achieve maximal inhibition by mAb 13.1 (activity was abrogated totally if PBL were removed). Together the data suggest that one of the mechanisms of action of this antibody is antibody-mediated PBL killing. Phagocytosis of parasites was noted in these experiments in all cultures. We have not attempted in this study to distinguish between Fc-mediated opsonization, as opposed to antibody-dependent cellular cytotoxicity.

Journal article

RANAWAKA GRR, ALEJOBLANCO AR, SINDEN RE, 1994, CHARACTERIZATION OF THE EFFECTOR MECHANISMS OF A TRANSMISSION-BLOCKING ANTIBODY UPON DIFFERENTIATION OF PLASMODIUM-BERGHEI GAMETOCYTES INTO OOKINETES IN-VITRO, PARASITOLOGY, Vol: 109, Pages: 11-17, ISSN: 0031-1820

Journal article

KUMAR S, VANPELT JF, ODOWD CA, HOLLINGDALE MR, SINDEN REet al., 1994, EFFECTS OF HORMONES AND CYSTEINE PROTEASE MODULATORS ON INFECTION OF HEPG2 CELLS BY PLASMODIUM-BERGHEI SPOROZOITES IN-VITRO DETERMINED BY ELISA IMMUNOASSAY, JOURNAL OF PARASITOLOGY, Vol: 80, Pages: 414-420, ISSN: 0022-3395

Journal article

Fowler RE, Billingsley PF, Pudney M, Sinden REet al., 1994, Inhibitory action of the anti-malarial compound atovaquone (566C80) against Plasmodium berghei ANKA in the mosquito, Anopheles stephensi., Parasitology, Vol: 108 ( Pt 4), Pages: 383-388, ISSN: 0031-1820

The activity of atovaquone against Plasmodium berghei ANKA during sporogonic development has been examined. Anopheles stephensi mosquitoes were fed on gametocyte infected mice which had been treated 8 h previously with atovaquone or diluent alone. Mosquito midguts were examined for oocysts, and salivary gland infections were estimated using an ELISA for the circumsporozoite protein (CSP). The number of oocysts per midgut fell by at least 97% when mosquitoes were fed on mice dosed with 0.1-10 mg atovaquone/kg body weight. This was paralleled by a decrease in the prevalence of oocyst-infected mosquitoes from 70-90% in controls to 40% or 10% respectively. No oocysts were observed at a dose of 100 mg/kg. CSP ELISA results indicated that mosquitoes fed on atovaquone failed to produce sporozoites. Mosquitoes which fed on gametocytaemic, atovaquone-treated mice (0.1-100 mg/kg) did not transmit malaria to naive mice. These results demonstrate that atovaquone has a highly potent inhibitory activity against the mosquito stages of P. berghei.

Journal article

FOWLER RE, BILLINGSLEY PF, PUDNEY M, SINDEN REet al., 1994, INHIBITOR ACTION OF THE ANTIMALARIAL COMPOUND ATOVAQUONE (566C80) AGAINST PLASMODIUM-BERGHEI ANKA IN THE MOSQUITO, ANOPHELES-STEPHENSI, PARASITOLOGY, Vol: 108, Pages: 383-388, ISSN: 0031-1820

Journal article

FLECK SL, BUTCHER GA, SINDEN RE, 1994, PLASMODIUM-BERGHEI - SERUM-MEDIATED INHIBITION OF INFECTIVITY OF INFECTED MICE TO ANOPHELES-STEPHENSI MOSQUITOS, EXPERIMENTAL PARASITOLOGY, Vol: 78, Pages: 20-27, ISSN: 0014-4894

Journal article

MATSUOKA H, PATON MG, BARKER GC, BLANCO ARA, SINDEN REet al., 1994, STUDIES ON THE IMMUNOGENICITY OF A RECOMBINANT OOKINETE SURFACE-ANTIGEN PBS21 FROM PLASMODIUM-BERGHEI EXPRESSED IN ESCHERICHIA-COLI, PARASITE IMMUNOLOGY, Vol: 16, Pages: 27-34, ISSN: 0141-9838

Journal article

JANSE CJ, PONZI M, SINDEN RE, WATERS APet al., 1994, CHROMOSOMES AND SEXUAL DEVELOPMENT OF RODENT MALARIA PARASITES, CEC/Latin-American Malaria Conference/IV CEC Makarua Contract Holders Meeting, Publisher: MEM INST OSWALDO CRUZ, Pages: 43-46, ISSN: 0074-0276

Conference paper

Barker GC, Rodríguez MH, Sinden RE, 1994, Attempted isolation of the gene encoding the 21 Kd Plasmodium berghei ookinete transmission blocking antigen from Plasmodium yoelli and Plasmodium vivax., Mem Inst Oswaldo Cruz, Vol: 89 Suppl 2, Pages: 37-41, ISSN: 0074-0276

The 21kD ookinete antigen of Plasmodium berghei (Pbs 21) has been shown to elicit an effective and long lasting transmission blocking immune response in mice. Having cloned and sequenced this antigen (Paton et al. 1993) the sequence was compared to the genes of the same family previously identified in P. falciparum, P. gallinaceum (Kaslow et al. 1989) and P. reichenowi (Lal et al. 1990). Four conserved areas were identified in this comparison, to which degenerate oligonucleotides were designed. PCR amplification and screening of genomic libraries was then carried out using these oligonucleotides. The P. yoelii gene was successfully cloned and a number of novel P. vivax genes identified but the P. vivax homologue of Pbs21 remains elusive.

Journal article

KOBAYASHI J, MATSUOKA H, CHINZEI Y, SINDEN RE, MIYAJIMA Set al., 1994, PRODUCTION OF A TRANSMISSION BLOCKING VACCINE CANDIDATE OF RODENT MALARIA PLASMODIUM-BERGHEI USING A BACULOVIRUS EXPRESSION VECTOR SYSTEM, 6th International Meeting of the Japanese-Association-for-Animal-Cell-Technology; Animal Cell Technology - Basic and Applied Aspects, Publisher: KLUWER ACADEMIC PUBL, Pages: 41-45

Conference paper

Janse CJ, Ponzi M, Sinden RE, Waters APet al., 1994, Chromosomes and sexual development of rodent malaria parasites., Mem Inst Oswaldo Cruz, Vol: 89 Suppl 2, Pages: 43-46, ISSN: 0074-0276

Journal article

BARKER GC, RODRIGUEZ MH, SINDEN RE, 1994, ATTEMPTED ISOLATION OF THE GENE ENCODING THE 21-KD PLASMODIUM-BERGHEI OOKINETE TRANSMISSION-BLOCKING ANTIGEN FROM PLASMODIUM-YOELLI AND PLASMODIUM-VIVAX, CEC/Latin-American Malaria Conference/IV CEC Makarua Contract Holders Meeting, Publisher: MEM INST OSWALDO CRUZ, Pages: 37-41, ISSN: 0074-0276

Conference paper

CRAMPTON JM, GALLER R, SINDEN RE, CRISANTI Aet al., 1993, THE GENETIC WAR AGAINST MOSQUITOS, RECHERCHE, Vol: 24, Pages: 1218-1227, ISSN: 0029-5671

Journal article

RANAWAKA G, ALEJOBLANCO R, SINDEN RE, 1993, THE EFFECT OF TRANSMISSION-BLOCKING ANTIBODY INGESTED IN PRIMARY AND SECONDARY BLOODFEEDS, UPON THE DEVELOPMENT OF PLASMODIUM-BERGHEI IN THE MOSQUITO VECTOR, PARASITOLOGY, Vol: 107, Pages: 225-231, ISSN: 0031-1820

Journal article

BUTCHER GA, COUCHMAN AF, VANPELT JF, FLECK SL, SINDEN REet al., 1993, THE SCID MOUSE AS A LABORATORY MODEL FOR DEVELOPMENT OF THE EXOERYTHROCYTIC STAGES OF HUMAN AND RODENT MALARIA, EXPERIMENTAL PARASITOLOGY, Vol: 77, Pages: 257-260, ISSN: 0014-4894

Journal article

Ranawaka G, Alejo-Blanco R, Sinden RE, 1993, The effect of transmission-blocking antibody ingested in primary and secondary bloodfeeds, upon the development of Plasmodium berghei in the mosquito vector., Parasitology, Vol: 107 ( Pt 3), Pages: 225-231, ISSN: 0031-1820

The effects of purified monoclonal immunoglobulins from control, or transmission-blocking anti-Pbs21 antibodies, upon the infection of Anopheles stephensi by ookinetes of Plasmodium berghei are compared. Anti-Pbs21 antibody reduced mean intensity and prevalence of infection by 94.7 and 58.7% respectively if added to the infectious bloodfeed at a concentration of 100 micrograms/ml. Fab fragments were of similar efficacy. No transmission enhancement was detected with declining antibody concentrations. Addition to subsequent (second) feeds reduced mean oocyst intensity but not prevalence. The reduction in blockade declined from 41% at day 2, to 4% at day 8. Second bloodfeeds, containing control globulin taken 4 or 6 days (but not 2 days) after infection, increased sporozoite burden in the salivary glands. At all times anti-Pbs21 reduced sporozoite number in the thorax compared to time-matched controls, but again highest gland intensities were obtained when the second bloodfeed was given on day 4. We conclude that second bloodfeeds containing transmission-blocking antibody simultaneously serve two opposing roles, (1) inhibition of parasite development and (2) the supply of nutrients which permit more sporozoites to be produced by each oocyst.

Journal article

Sinden RE, Barker GC, Paton MJ, Fleck SL, Butcher GA, Waters A, Janse CJ, Rodriguez MHet al., 1993, Factors regulating natural transmission of Plasmodium berghei to the mosquito vector, and the cloning of a transmission-blocking immunogen., Parassitologia, Vol: 35 Suppl, Pages: 107-112, ISSN: 0048-2951

Naturally occurring factors that regulate the infectivity of P. berghei infected rodent hosts to the mosquito vector in vivo have been compared in T.O., Balb/C and immunodeficient SCID mice. No detectable differences in infectivity were observed suggesting B and T cell mediated factors are not involved. Further studies investigated roles for macrophage colony stimulating factors, the cytokines IFN gamma and TNF alpha, of neutrophils, and of nitric oxide in the SCID mouse, but have failed to demonstrate an important role in vivo for any factor examined. Differences between these results and those obtained in vitro on the human and primate parasites must therefore be explained by biological differences between the parasite/host combinations, or by technical differences in experimental designs. Induced immunity to the ookinete surface antigen Pbs 21 of P. berghei can totally block the transmission of the parasite from the gametocyte infected host to the vector. We have cloned the gene encoding Pbs 21 and shown it bears striking structural similarities to Pfs 25, Pgs 25 and more particularly Pgs 28 in that it has a high cysteine content (9.5%), 4 EGF-like domains and hydrophobic amino-'signal'--and carboxyl-'anchor' sequences. The encoding gene is on chromosome 5 and is found also in P. chabaudi, P. yoelii and P. vinckei.

Journal article

MULLER HM, CRAMPTON JM, DELLATORRE A, SINDEN R, CRISANTI Aet al., 1993, MEMBERS OF A TRYPSIN GENE FAMILY IN ANOPHELES-GAMBIAE ARE INDUCED IN THE GUT BY BLOOD MEAL, EMBO JOURNAL, Vol: 12, Pages: 2891-2900, ISSN: 0261-4189

Journal article

Medley GF, Sinden RE, Fleck S, Billingsley PF, Tirawanchai N, Rodriguez MHet al., 1993, Heterogeneity in patterns of malarial oocyst infections in the mosquito vector., Parasitology, Vol: 106 ( Pt 5), Pages: 441-449, ISSN: 0031-1820

Oocyst prevalence and intensity have been recorded in 349 laboratory infections of Anopheles stephensi with Plasmodium berghei. Intensity and prevalence of infection are shown to be predictably related. The structure and heterogeneity in the infections has been analysed with the objective of describing the biological mechanisms by which the observed negative binomial oocyst distributions are generated. The analysis has revealed that the most likely processes lie within the population dynamic events of malaria within the mosquito, namely gametogenesis, fertilization and mortality. The distribution is similar in all Plasmodium-mosquito combinations examined so far, whether they are of laboratory (P. gallinaceum in Aedes aegypti) or field (P. vivax in An. albimanus and P. falciparum in An. gambiae s.l. and An. funestus) origin. Further we conclude that there is competition between parasites in the vector. Oocyst frequency distribution analysis shows that under natural conditions of transmission intensity, and even under the best laboratory conditions, significant numbers (> 10%) of fully susceptible mosquitoes will not be infected under conditions where the mean infection is as high as 250 oocysts. Failure to infect is not therefore an absolute indicator of refractoriness. In assessing transmission data it is shown that sample sizes should not be less than 50, and ideally 100 mosquitoes, if reliable data are to be obtained. In field it is suggested that difficulties in determining the low natural intensity of oocyst infections indicate that prevalence estimates are a useful and accessible parameter to measure.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal article

MEDLEY GF, SINDEN RE, FLECK S, BILLINGSLEY PF, TIRAWANCHAI N, RODRIGUEZ MHet al., 1993, HETEROGENEITY IN PATTERNS OF MALARIAL OOCYST INFECTIONS IN THE MOSQUITO VECTOR, PARASITOLOGY, Vol: 106, Pages: 441-449, ISSN: 0031-1820

Journal article

PATON MG, BARKER GC, MATSUOKA H, RAMESAR J, JANSE CJ, WATERS AP, SINDEN REet al., 1993, STRUCTURE AND EXPRESSION OF A POSTTRANSCRIPTIONALLY REGULATED MALARIA GENE ENCODING A SURFACE PROTEIN FROM THE SEXUAL STAGES OF PLASMODIUM-BERGHEI, MOLECULAR AND BIOCHEMICAL PARASITOLOGY, Vol: 59, Pages: 263-275, ISSN: 0166-6851

Journal article

Hollingdale MR, Sinden RE, van Pelt J, 1993, Sporozoite invasion., Nature, Vol: 362, ISSN: 0028-0836

Journal article

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