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Biomedical subjects

I Denholm

Publications and source records attributed to I Denholm.

23 records · Page 2Linked to original sources

Knockdown resistance (kdr) to DDT and pyrethroid insecticides maps to a sodium channel gene locus in the housefly (Musca domestica).

The voltage-sensitive sodium channel is generally regarded as the primary target site of dichloro-diphenyl-trichloro-ethane (DDT) and pyrethroid insecticides, and has been implicated in the widely reported mechanism of nerve insensitivity to these compounds. This phenomenon is expressed as knockdown resistance (kdr) and has been best characterised in the housefly where several putative alleles, including the more potent super-kdr factor, have been identified. We report the isolation of cDNA clones containing part of a housefly sodium channel gene, designated Msc, which show close homology to the para sodium channel of Drosophila (99% amino acid identity within the region of overlap). Using Southern blots of insect DNA, restriction fragment length polymorphisms (RFLPs) at the Msc locus were identified in susceptible, kdr and super-kdr housefly strains. These RFLPs showed tight linkage to resistance in controlled crosses involving these strains, thus providing clear genetic evidence that kdr, and hence pyrethroid mode of action, is closely associated with the voltage-sensitive sodium channel.

Amino Acid Sequence↗

Macrophage migration and maturation within rheumatoid nodules.

In long-established rheumatoid nodules, monocytes continue to be recruited and to migrate from the outer vascular zone toward the palisade and central necrotic area. Maturation of these cells is shown to take place during tissue migration. We found that the great majority of palisade cells express exclusive mononuclear phagocyte phenotypes. Among this mononuclear phagocyte population are many cells that bear the receptor for iC3b (CR3), but few that bear the receptor for C3b (CR1). HLA-D region molecule expression is intense and widespread.

Aged↗

Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules.

The mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.

Aged↗

Adaptation of insects to insecticides.

Insects have successfully adapted to most insecticides by becoming resistant to them. This adaptation, of recent origin, has evolved rapidly and independently in a large number of species and is of serious economic and medical importance. The origins of resistance are still obscure, but resistance is assumed to be pre-adaptive, arising through recurrent mutation of existing alleles. However, in at least one well-researched case it probably originated by gene duplication. Resistance can be monofactorial or multifactorial. When several independent mechanisms confer resistance to the same group of insecticides the order in which these mechanisms are selected may reflect their effectiveness in protecting insects from the toxic effects of the different compounds. Our concept of resistance is changing as insects continue to adapt to the insecticide-containing environment. Criteria for defining resistance in both fundamental and practical terms are re-examined here in the light of recent work.

Adaptation, Biological↗