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Biomedical subjects

P R Weldon

Publications and source records attributed to P R Weldon.

10 recordsLinked to original sources

An ultrastructural investigation of Leishmania donovani infection in genetically resistant and susceptible mouse strains.

Natural resistance to the growth of Leishmania donovani in mice is controlled by a gene (Lsh) which is expressed, in an unknown fashion, in macrophages. Early net growth rate of the parasite is much higher in mice strains bearing the susceptible allele (Lshs) than in resistant (Lshr) mice. Intracellular events occurring in the Kupffer cells during this period have been studied at the ultrastructural level. It was found that the number of dividing amastigotes per thin section of infected cell was approximately 10-fold greater in susceptible (B10.A SgSn) than in resistant (A/J) strains of mice, both 7 and 14 days following infection. These findings support the hypothesis that high natural resistance to leishmaniasis (Lshr) is expressed as a microbistatic effect, exerted within the parasitized macrophage of the host.

Animals

Cholinesterase localization at sites of nerve contact on embryonic amphibian muscle cells in culture.

Cholinesterase (ChE), detected histochemically, was found to be localized at many sites of nerve-muscle contact in cultures of spinal cord and muscle cells derived from Xenopus laevis embryos. Such contacts were often characterized by a corresponding localization of acetylcholine receptors and by synaptic ultrastructure, including aggregates of clear vesicles in the nerve fibre and an 80-100 nm wide intercellular cleft. The ChE reaction product was localized in the cleft. When cultures were grown in the presence of curare many of the nerve-contacted muscle cells still exhibited ChE at the sites of contact. It is concluded that ChE accumulates at synaptic contacts in these cultures even in the absence of muscle action potentials and contraction.

Animals

Localization of acetylcholine receptors and synaptic ultrastructure at nerve-muscle contacts in culture: dependence on nerve type.

In cultures of xenopus myotomal muscle cells and spinal cord (SC) some of the nerve-muscle contacts exhibit a high density of acetylcholine receptors (AchRs [Anderson et al., 1977, J. Physiol. (Lond.). 268:731- 756,757-773]) and synaptic ultrastructure (Weldon and Cohen, 1979, J. Neurocytol. 8:239-259). We have examined whether similarly specialized contacts are established when the muscle cells are cultured with explants of xenopus dorsal root ganglia (DRG) or sympathetic ganglia (SG). The outgrowth from the ganglionic explants contained neuronal and non- neuronal cell processes. Although both types of processes approached within 100 A of muscle cells, synaptic ultrastructure was rarely observed at these contacts. Because patches of postsynaptic ultrastructure also develop on noncontacted muscle cells, the very few examples of contacts with such specializations probably occurred by chance. AChRs were stained with fluroscent alpha-bungarotoxin. More than 70 percent of the SC-contacted muscle cells exhibited a high receptor density along the path of contact. The corresponding values for DRG- and SG- contacted muscle cells were 10 and 6 percent. Similar values were obtained when the ganlionic and SC explants were cultured together in the same chamber. The few examples of high receptor density at ganglionic-muscle contacts resembled the characteristic receptor patches of noncontacted muscle cells rather than the narrow bands of high receptor density seen at SC-muscle contacts. In addition, more than 90 percent of these ganglionic- contacted muscle cells had receptor patches elsewhere, compared to less than 40 percent for the SC-contacted muscle cells. These findings indicate that the SC neurites possess a specific property which is important for the establishment of synaptically specialized contacts with muscle and that this property is lacking in the DRG and SG neurites.

Animals

Development of synaptic ultrastructure at neuromuscular contacts in an amphibian cell culture system.

Cultures of dissociated myotomal muscle and spinal cord derived from embryos of Xenopus laevis were grown in the presence of curare in order to abolish neuromuscular activity and were examined by electron microscopy. In one-day-old cultures a few of the neuromuscular contacts already displayed several synaptic specializations including 500 A vesicles clustered against the axolemma, increased axolemmal densities, basal lamina in the cleft, an increased sarcolemmal density and subsarcolemmal filamentous material. Contacts with these specializations were observed more frequently in two and three-day-old cultures. Throughout the three-day culture period nerve fibres and neuromuscular contacts were devoid of Schwann cells. Isolated patches of basal lamina were relatively scarce and were usually accompanied by an increase in sarcolemmal density and subsarcolemmal filamentous material even in cultures in which spinal cord cells were not included. These observations indicate that the myotomal neuromuscular synapse differentiates in culture in much the same way as it does in vivo, that muscle contractions are not required for its differentiation, and that apparent postsynaptic specializations can develop in the absence of innervation.

Animals

Pinocytotic uptake and intracellular distribution of colloidal thorium dioxide by cultured sensory neurites.

Sensory ganglia from 9-day chick embryos were grown on collagen coated coverslips for36 h in the presence of nerve growth factor, producing a profuse neuritic outgrowth. The cultures were then incubated for varying periods in a colloidal suspension of thorium dioxide, and the pinocytotic uptake of this marker was followed by electron microscopy. Following brief exposures (3 min), most of the labelled organelles consisted of smooth surfaced vesicles and vacuoles; with longer exposures, the bulk of the marker accumulated first in cup-shaped pre-multivesticular bodies and ultimately in multivesicular bodies. The marker was also taken up into coated vesicles, dense-cored and electron lucent tubules,dense-cored vesicles and dense bodies of the multi-layered myelin body configuration. In addition, evidence suggestive of exocytosis was also obtained; views of apparent fusion of labelled multivesicular bodies with the plasmalemma involving extrusion of vesiclesand marker particles into the extracellular space were regularly encountered following long exposures.

Animals