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Biomedical subjects

G Horsburgh

Publications and source records attributed to G Horsburgh.

8 recordsLinked to original sources

The effect of UVB irradiation on antibody responses during herpes simplex virus type 1 (HSV-1) infections of mice.

Ultraviolet B (UVB) exposure suppresses cell-mediated immunity and may alter the cytokine profile, reducing T helper 1 (Th1) cytokines and promoting Th2 cytokines. Th1 cytokines enhance the production of immunoglobulin (Ig) G2a, IgG2b and IgG3 antibodies, while Th2 cytokines enhance the production of IgG1 and IgE antibodies. The effect of suberythemal UVB irradiation on antibody isotypes following infection of C3H/HeN mice with herpes simplex virus (HSV) was investigated using two protocols. First, mice were irradiated prior to two subcutaneous infections with HSV. Second, mice were immunised with inactivated HSV before being irradiated and challenged epidermally with HSV, which led to an increase in the size of the clinical lesions compared with unirradiated animals. In both models, the HSV-specific IgG titre was not affected by the UVB exposure but, generally, the irradiated animals showed a small reduction in both Th1- and Th2-associated HSV antibody isotypes. IL-4 knockout (IL-4-/-) mice were used to investigate the role of IL-4 in UVB-induced isotype switching. Here IL-4-/- and IL-4+/+ strains were irradiated prior to primary and secondary epidermal infections with HSV, followed by measurement of antibody titres and lesion size. In both the mutant and parent mice, UV irradiation led to an increase in lesion severity. In IL-4+/+ mice, UV exposure did not affect the HSV titre of any of the individual isotypes tested but did suppress the total IgG to HSV This suppression may be due to UV-induced IL-4 release because, in the IL-4-/- mice, HSV IgG was elevated by the UVB irradiation. If UV modulates the immune response solely via the action of cytokines, then the downregulation of Th1 cytokines and upregulation of Th2 cytokines should be accompanied by antibody isotype switching from IgG2a and IgG3 towards IgG1 and IgE. This result was not obtained in the models tested, perhaps because HSV infection promotes such a complex array of innate and acquired immune responses that a clear effect on virus-specific isotype production may not be apparent.

Animals↗

Topography of developing thalamic and cortical pathways in the visual system of the cat.

Adult patterns of connectivity could emerge during development by a process of selective elimination from an earlier, more widespread, connectivity. We have addressed this issue by examining the topography of developing projections to area 17 in the cat. At different postnatal ages, paired injections of the retrograde tracers diamidino yellow and fast blue were made in area 17. Interinjection separations were carefully controlled and the spatial distribution of the two populations of labelled neurones investigated. Projections to the striate cortex from the lateral geniculate nucleus, area 18, as well as connections intrinsic to area 17 were analysed quantitatively with a graphic method that uses a two-dimensional model of the projection. This allows two parameters of the projection to be calculated: the divergence (the spatial extent of area 17 contacted by an infinitely small region of an afferent structure) and the convergence (the extent of an afferent structure that projects to an infinitely small region of area 17). During postnatal development, the bulk of the connections making up the geniculostriate and corticocortical pathways showed no variation either in their convergence and divergence. However, the projection of area 18 to area 17 and the intrinsic area 17 connections (but not the geniculostriate projection) in the 3-15-day-old kittens were each found to contain a small subpopulation of widely scattered neurones with widespread axonal trajectories. These results, showing that many initially formed connections display a high degree of topographical order, are discussed in terms of the control mechanisms specifying axonal trajectories during development.

Aging↗

The effects of bilateral enucleation in the primate fetus on the parcellation of visual cortex.

Bilateral enucleation in the macaque fetus causes an areal reduction of an otherwise normal striate cortex. Here we show that in early operated animals this reduction is accompanied by a separation of striate and prostriate cortices which are normally contiguous. However this induced separation does not correspond to the areal reduction of striate cortex, indicating that extrinsic signals regulate either the proliferation and/or survival of striate cortical neurons.

Animals↗

Maturation and connectivity of the visual cortex in monkey is altered by prenatal removal of retinal input.

In several species, the peripheral input from the eyes partly determines the pattern of interconnections between the visual areas of the two cerebral hemispheres through the fibre tract termed the corpus callosum. In the macaque monkey, the neurons projecting through the callosum are largely restricted to area 18 throughout ontogeny, whereas area 17 is characterized by few or no callosal projections. Here, we show that suppressing the peripheral input by prenatal removal of the eyes leads to a marked reduction in the extent of area 17, resulting in a large shift in the position of the histologically identifiable boundary between the two areas. Even so, the boundary continues to separate an area rich with callosal connections (area 18) from one poor in such projections (area 17), indicating there is no effect on the callosal connectivity of area 17. In contrast, in area 18, eye removal results in many more neurons with callosal projections than in normal animals. The results suggest that the factors that determine the parcellation of cortical areas also specify their connectivity.

Animals↗

Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities.

Small eye (Sey) is a dominant mutation in the mouse affecting the embryonic development of the eyes and nose. In homozygous Sey/Sey embryos, the optic vesicles grow out but there is no lens induction and the nasal pits fail to develop. Scanning electron microscope studies of Sey/Sey embryos show that the maxillary processes develop normally and fuse with ridges of ectoderm in the frontonasal position. In Sey/+ heterozygotes, the vacuolated lens is smaller than normal, and there is folding of the margins of the optic cup and ingrowth of mesodermal cells. Evidence is presented that Sey is not allelic with Coloboma (Cm), another mutation affecting eye development on chromosome 2.

Animals↗

Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse.

Small eyes (Sey) is a semidominant, homozygous lethal mutation in the mouse (Roberts, 1967). It is allelic with SeyH, a radiation-induced homozygous prenatal lethal which has been mapped on chromosome 2. The effect of the Sey mutation is apparently limited to the growth and differentiation of the presumptive lens and nasal placodes. Homozygous Sey/Sey embryos can be distinguished as early as 10.5 days post coitum (p.c.); the optic vesicles grow out, but the ectoderm does not give rise to a lens and nasal pits never form. Immunohistochemical studies show that the distribution of the extracellular matrix glycoprotein laminin is not significantly different in the cephalic region of Sey/Sey versus Sey/+ or +/+ embryos. Sey/Sey embryos develop to term but without eyes or nose, and die soon after birth. Further analysis of Sey/Sey embryos may throw light on the mechanisms underlying morphogenesis of craniofacial structures in mammals.

Animals↗