Biomedical subjects

David Knox

Publications and source records attributed to David Knox.

4 recordsLinked to original sources

PubMed2005

Pinpointing and preventing imminent extinctions.

Slowing rates of global biodiversity loss requires preventing species extinctions. Here we pinpoint centers of imminent extinction, where highly threatened species are confined to single sites. Within five globally assessed taxa (i.e., mammals, birds, selected reptiles, amphibians, and conifers), we find 794 such species, three times the number recorded as having gone extinct since 1500. These species occur in 595 sites, concentrated in tropical forests, on islands, and in mountainous areas. Their taxonomic and geographical distribution differs significantly from that of historical extinctions, indicating an expansion of the current extinction episode beyond sensitive species and places toward the planet's most biodiverse mainland regions. Only one-third of the sites are legally protected, and most are surrounded by intense human development. These sites represent clear opportunities for urgent conservation action to prevent species loss.

Animals↗

PubMed2003

Progress in the development of a recombinant vaccine for human hookworm disease: the Human Hookworm Vaccine Initiative.

Hookworm infection is one of the most important parasitic infections of humans, possibly outranked only by malaria as a cause of misery and suffering. An estimated 1.2 billion people are infected with hookworm in areas of rural poverty in the tropics and subtropics. Epidemiological data collected in China, Southeast Asia and Brazil indicate that, unlike other soil-transmitted helminth infections, the highest hookworm burdens typically occur in adult populations, including the elderly. Emerging data on the host cellular immune responses of chronically infected populations suggest that hookworms induce a state of host anergy and immune hyporesponsiveness. These features account for the high rates of hookworm reinfection following treatment with anthelminthic drugs and therefore, the failure of anthelminthics to control hookworm. Despite the inability of the human host to develop naturally acquired immune responses to hookworm, there is evidence for the feasibility of developing a vaccine based on the successes of immunising laboratory animals with either attenuated larval vaccines or antigens extracted from the alimentary canal of adult blood-feeding stages. The major antigens associated with each of these larval and adult hookworm vaccines have been cloned and expressed in prokaryotic and eukaryotic systems. However, only eukaryotic expression systems (e.g., yeast, baculovirus, and insect cells) produce recombinant proteins that immunologically resemble the corresponding native antigens. A challenge for vaccinologists is to formulate selected eukaryotic antigens with appropriate adjuvants in order to elicit high antibody titres. In some cases, antigen-specific IgE responses are required to mediate protection. Another challenge will be to produce anti-hookworm vaccine antigens at high yield low cost suitable for immunising large impoverished populations living in the developing nations of the tropics.

Adolescent↗

PubMed2002

The proteinases of Psoroptes ovis, the sheep scab mite--their diversity and substrate specificity.

The sheep scab mite, Psoroptes ovis, causes severe dermatitis in infected sheep with severe welfare and production implications. The dermatitis has the characteristics of an immediate hypersensitivity type reaction which, by analogy to other mite species, including the house dust mites (Dermatophagoides spp.), is likely to be invoked by a variety of allergens including mite-derived proteinases. Here, the proteinases in P. ovis extracts were characterised using substrate gel analysis, inhibitor sensitivity and their ability to degrade a variety of potential natural protein substrates. These analyses showed that mites contain several proteinases which could be differentiated on the basis of molecular size and inhibitor sensitivity with cysteine, metalloproteinases and aspartyl proteinases predominating. These proteinases degraded collagen and fibronectin, possibly indicative of a role in lesion initiation, they degraded several blood proteins, a property which may aid mite feeding and they degraded immunoglobulin G, possibly aiding immuno-evasion. Because proteinases, particularly the cysteine class, are demonstrably allergenic in other mite infestations, these proteinases clearly merit further immunological and biochemical definition.

Animals↗

PubMed2002

Distinct characteristics of two intestinal protein compartments discriminated by using fenbendazole and a benzimidazole resistant isolate of Haemonchus contortus.

The intestine of Haemonchus contortus is hypersensitive to the effects of the anthelmintic fenbendazole (FBZ). The effects are postulated to stem from disruption of microtubules and interference with apical secretory vesicle transport, followed by release of digestive enzymes into the intestinal cell cytoplasm. Here, FBZ caused marker proteins for both apical (pepsinogen-like protease, PEP-1) and basal (cystatin-like protein) protein compartments to became homogeneously distributed in the cytoplasm of H. contortus intestinal cells. The observations with PEP-1 support the hypothesis that release of hydrolytic enzymes into the intestinal cell cytoplasm contributes to the mechanism of benzimidazole efficacy. A benzimidazole resistant isolate of H. contortus expressed type 1 and 2 intestinal beta-tubulin transcripts that would encode predominantly tyr200 and phe200 variants, respectively. This isolate was resistant to the known intestinal cell alterations induced by FBZ treatment in the susceptible isolate, including inhibition of apical vesicle transport. These results implicate type 1 beta-tubulin in mediating apical vesicle transport in intestinal cells and suggest that the tyr200 variant is a determinant of FBZ resistance in intestinal cells. In contrast, the basal protein compartment demonstrated sensitivity to FBZ treatment in these otherwise "resistant" worms. Hence, distinct FBZ-sensitive components appear to be involved in distributing intestinal proteins into the described apical and basal compartments of normal worms.

Animals↗