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Biomedical subjects

G C Barker

Publications and source records attributed to G C Barker.

27 records · Page 2Linked to original sources
PubMed1993

Factors regulating natural transmission of Plasmodium berghei to the mosquito vector, and the cloning of a transmission-blocking immunogen.

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.

Amino Acid Oxidoreductases↗
PubMed1991

The effect of ecdysteroids on the microfilarial production of Brugia pahangi and the control of meiotic reinitiation in the oocytes of Dirofilaria immitis.

The effects of the ecdysteroids ecdysone and 20-hydroxyecdysone on microfilarial release in Brugia pahangi and on meiotic reinitiation in the oocytes of Dirofilaria immitis were studied. Ecdysone was found to stimulate microfilarial release at 2 x 10(-6) M, but this effect was reduced at higher and lower concentrations. 20-Hydroxyecdysone was found to have no such effect. In D. immitis, ecdysone at 10(-5) M was also found to overcome the period of meiotic arrest that occurs during the pachytene stage of prophase 1. This effect was reduced when 10(-6) M ecdysone was used. These results help support the theory that the ecdysteroids play a hormonal role in filarial worms similar to that found in insects.

Animals↗
PubMed1990

Investigation of ecdysteroid excretion by adult Dirofilaria immitis and Brugia pahangi.

The excretion of ecdysteroids by the filarial nematode species, Dirofilaria immitis and Brugia pahangi, was examined both in vitro, by the analysis of culture medium, and in vivo, through analysis of serum samples from experimentally infected hosts. There was no evidence of ecdysteroid excretion by intact parasites of either species in vitro. Free ecdysteroids were detected in the serum of ferrets and dogs infected with D. immitis, but concentrations would be at or below the limit of detection in sub-millilitre serum samples. The detection of ecdysteroids in the serum of potential hosts is unlikely to be of value in the diagnosis of filarial infections due to a combination of low titre in the presence of current infection and measurable titre in its absence. Ecdysteroids of dietary origin may contribute to the latter.

Animal Feed↗
PubMed1990

Ecdysteroids in nematodes.

The occurrence of ecdysteroids (insect moulting hormones) in nematodes, albeit at low concentrations, has been firmly established. In addition to apparently stimulating moulting in a few species, exogenously applied ecdysteroids have now been shown to have interesting biological effects on meiotic reinitiation in oocytes and on microfilarial production in filariae. Although such effects demonstrate the feasibility of influencing nematode physiology with exogenously applied ecdysteroids, hitherto it has not been possible to demonstrate synthesis de novo of these steroids in nematodes. Thus, it remains to be established whether ecdysteroids are truly endogenous nematode hormones or merely represent compounds with strong biological activity. Nonetheless, there are indications that interference with the ecdysteroid system might be exploitable in the development of novel approaches to control of nematodes.

Journal Article↗
PubMed1989

Effects of potential inhibitors on Brugia pahangi in vitro: macrofilaricidal action and inhibition of microfilarial production.

A series of compounds that apparently disrupt hormonally regulated processes in insects have been examined for effects on the viability and microfilarial production of adult Brugia pahangi cultured in vitro. The azasteroids, 25-azacoprostane and 25-azacholestane, inhibited the production of microfilariae at 5 ppm, the former also exhibiting macrofilaricidal activity at this concentration. The brassinosteroids examined inhibited microfilarial production at 5 ppm but did not affect worm viability. Azadirachtin also proved to be a significant inhibitor of microfilarial release without effect on worm motility or viability. Of all the compounds tested, the non-steroidal amines appeared to be the most promising as potential filaricides, several of them proving to be macrofilaricidal at 1 ppm and affecting microfilarial production at even lower concentrations.

Amines↗
PubMed1989

Studies on the biosynthesis and fate of ecdysteroids in filarial nematodes.

Experiments were performed to investigate whether adult Dirofilaria immitis and Brugia pahangi were capable of synthesising ecdysteroids from cholesterol or various intermediates from the biosynthetic pathway functioning in insects. Metabolites of radioactively-labelled cholesterol and 5 beta-ketodiol (2,22,25-trideoxy-ecdysone) were detected in the filarial nematodes, but there was no radioactivity corresponding to ecdysteroid. Uptake of tritiated 2-deoxyecdysone was poor and metabolism was not observed. [3H]Ecdysone was absorbed sparingly by adult D. immitis, but was metabolised efficiently to several less polar products. There was no evidence of C-20 hydroxylation capability.

Animals↗
PubMed1989

Analysis of ecdysteroids in Onchocerca gibsoni, O. volvulus and nodule tissues.

Free ecdysteroids were detected in Onchocerca gibsoni, in tissues constituting O. volvulus and O. gibsoni nodules and in unrelated bovine tissues. Ecdysone and 20-hydroxyecdysone were identified by HPLC-RIA and GC/MS(SIM). The concentration of free ecdysteroids in the nodule tissue immediately surrounding the parasites was at least an order of magnitude higher than that detected in the worms themselves, or in adjacent nodular tissues or other bovine tissues.

Abattoirs↗
PubMed1987

Dosage, timing, and route of administration of cyclosporin A and nonimmunosuppressive derivatives of dihydrocyclosporin A and cyclosporin C against Schistosoma mansoni in vivo and in vitro.

The prophylactic and therapeutic effects of cyclosporin A (CsA) against percutaneous Schistosoma mansoni infection in MF1 mice were dose related and dependent on the temporal relationship between drug administration and infection. Antischistosomal activity, assessed by worm recovery from the host 6 weeks after infection, was most effective (complete worm elimination) when CsA was administered at the time of infection. Oral administration of CsA was less effective than subcutaneous injection, and no prophylactic activity was demonstrated by the former route. Derivatives of dihydrocyclosporin A and cyclosporin C, which have been reported to exert only poor immunosuppressive activity, exhibited efficacy against S. mansoni similar to that of CsA and were also less effective when given orally. Subcutaneous, but not oral CsA reduced cercarial skin penetration and transformation success; the derivative of dihydrocyclosporin A, however, was without effect. Moreover, CsA, but not the derivative of dihydrocyclosporin A, reduced the number of worms established after intraperitoneal injection of cercariae. These data provide further insight into the antischistosomal activity of cyclosporins, which appears to be distinct from their immunomodulatory properties, since parasite killing was retained both in immunologically disparate mice and with poorly immunosuppressive cyclosporin derivatives.

Animals↗