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R Curtis

Publications and source records attributed to R Curtis.

At least 19 recordsLinked to original sources
PubMed1992

Electron microscopic immunocytochemistry of GAP-43 within proximal and chronically denervated distal stumps of transected peripheral nerve.

Growth-associated protein, GAP-43 was initially described as a neuron-specific molecule thought to play a critical role in axonal growth and regeneration. However, it is also expressed in vitro in certain CNS glia, Schwann cell precursors and non-myelinating Schwann cells. In this paper, we report the subcellular localization of GAP-43 in vivo in chronically-denervated Schwann cells in the distal stumps of previously transected rat sciatic nerve. We have used a progressive lowering of temperature method combined with the non-polar acrylic resin Lowicryl HM20 and a post-embedding labelling regime to visualize the distribution of GAP-43, S-100 (marker for Schwann cells), RT97 and NF68 (markers for different subunits of the neurofilament molecule). We report that (1) the smallest calibre regrowing axons were GAP-43-positive, sometimes NF68-positive but always RT97-negative; (2) regenerating myelinated axons and larger unmyelinated axons (> 0.7 microns diameter) were NF68-positive, RT97-positive but GAP-43-negative; (3) cytoplasmic processes within Schwann cell basal lamina tubes in the distal stumps were S-100-positive, GAP-43-positive but RT97- and NF68-negative. The similar localization of GAP-43 within regrowing axons and denervated Schwann cells suggests that GAP-43 may function similarly in both situations, and may thus be involved in motility and/or elongation of axons and Schwann cells during regeneration.

Animals↗
PubMed1992

GAP-43 immunoreactivity is widespread in the autonomic neurons and sensory neurons of the rat.

GAP-43 is a membrane-bound phosphoprotein generally associated with axon growth during development and regeneration. Using immunohistochemical and immunoblotting techniques this study shows that GAP-43 is expressed extensively in the unperturbed adult autonomic nervous system. Strong immunoreactivity was seen in the developing and mature enteric subdivision of the autonomic nervous system and in nerves of the iris and various blood vessels. The presence of GAP-43 immunoreactivity in varicose nerve fibres, and a comparison of the labelling pattern of GAP-43 with the nerve associated marker PGP 9.5 suggests that GAP-43 is present in most or all autonomic nerve fibres in these organs. Immunoblotting of gut samples on 10% polyacrylamide gels revealed a single band of approximately 45,000 mol. wt that co-migrated with pure central nervous system GAP-43. Surgical sympathectomy experiments resulting in almost complete elimination of sympathetic fibres did not markedly affect the pattern of GAP-43 immunoreactivity in the iris, indicating that GAP-43 is expressed not only in sympathetic nerves but also in parasympathetic and sensory fibres. These findings show that GAP-43 is expressed extensively in autonomic nerves of the adult rat, at levels comparable to those seen during development. High levels of GAP-43 are not therefore restricted to development and regeneration in this part of the nervous system.

Animals↗
PubMed1992

GAP-43 is expressed by nonmyelin-forming Schwann cells of the peripheral nervous system.

Recently it has been demonstrated that the growth-associated protein GAP-43 is not confined to neurons but is also expressed by certain central nervous system glial cells in tissue culture and in vivo. This study has extended these observations to the major class of glial cells in the peripheral nervous system, Schwann cells. Using immunohistochemical techniques, we show that GAP-43 immunoreactivity is present in Schwann cell precursors and in mature non-myelin-forming Schwann cells both in vitro and in vivo. This immunoreactivity is shown by Western blotting to be a membrane-associated protein that comigrates with purified central nervous system GAP-43. Furthermore, metabolic labeling experiments demonstrate definitively that Schwann cells in culture can synthesize GAP-43. Mature myelin-forming Schwann cells do not express GAP-43 but when Schwann cells are removed from axonal contact in vivo by nerve transection GAP-43 expression is upregulated in nearly all Schwann cells of the distal stump by 4 wk after denervation. In contrast, in cultured Schwann cells GAP-43 is not rapidly upregulated in cells that have been making myelin in vivo. Thus the regulation of GAP-43 appears to be complex and different from that of other proteins associated with nonmyelin-forming Schwann cells such as N-CAM, glial fibrillary acidic protein, A5E3, and nerve growth factor receptor, which are rapidly upregulated in myelin-forming cells after loss of axonal contact. These observations suggest that GAP-43 may play a more general role in the nervous system than previously supposed.

Animals↗
PubMed1991

Changes in a photoreceptor polypeptide correlating with an early-onset retinal dystrophy in the cat.

A preparation of rod outer segments has been used to study the polypeptides characteristic of an early-onset retinal dystrophy in cats (Rdy) by two-dimensional gel electrophoresis. Comparison of 2-D gels of rod outer segment preparations from retinas of normal and Rdy animals shows several differences. In particular, a polypeptide of Mr 51 kDa and pI 7.5 is present at increased levels in preparations from Rdy cats at 6 weeks, 9 weeks and 12.5 weeks of age but not at 3.5 weeks.

Animals↗
PubMed1991

Autosomal dominant rod-cone dysplasia in the Rdy cat. 2. Electrophysiological findings.

Electroretinography was performed on cats affected with autosomal dominant rod-cone dysplasia (gene symbol Rdy). In normal kittens it was found that retinal sensitivity increased and rod thresholds decreased as the animals matured. Electroretinogram (ERG) amplitudes were mature by 4.5 weeks and adult timing was attained by 6 weeks of age, consistent with the findings of other workers. In Rdy-affected heterozygous kittens the ERG was absent or barely recordable using conventional corneal contact lens electrodes. However, the enhanced sensitivity of an intravitreal needle electrode permitted the recording of ERGs from affected kittens aged 4.5 weeks and older. The intravitreally recorded scotopic ERG in Rdy-affected kittens was a very low amplitude, largely negative response with prolonged a- and b-wave times-to-peak (two to threefold longer than in comparable recordings from an age-matched normal kitten). The b-wave lacked oscillatory potentials and was relatively small so that the ERG was a-wave dominated. This was attributed to delayed and defective synaptogenesis in the outer plexiform layer of dystrophic retinas. In contrast to normal kittens, the b-wave threshold was higher than that of the a-wave in affected kittens. Photopic responses were unrecordable. The intravitreal ERG was barely recordable in a 5-month-old Rdy-affected cat and was apparently extinguished by 7 months of age. In vitro electroretinography permitted a comparison of the photoreceptor responses (fast PIII) from the isolated retinas of 6-week-old control and Rdy-affected heterozygous kittens. Maximum fast PIII amplitudes were reduced by about 75% in affected retinas compared with age-matched normal retinas (P less than 0.005). The mean fast PIII time-to-peak, at maximum light intensity, in Rdy-affected retinas was prolonged by about 15 msec and was approximately twofold longer than the time-to-peak of normal retinas (P less than 0.005).4+ steeper slope with relatively greater prolongations in time-to-peak at lower luminances compared with normal retinas (P less than 0.025). These changes in temporal characteristics may be explained either by severe disorganization of photoreceptor outer segments or by altered phototransduction kinetics.

Aging↗
PubMed1991

Organizing as a new approach to AIDS risk reduction for intravenous drug users.

This paper looks at an innovative approach to AIDS risk reduction among intravenous drug users who are not in treatment. The new method utilizes an organizing model that involves the mobilization of drug users to promote risk reduction. This strategy targets the group as well as the individual for change. Standard outreach techniques have had some success in achieving HIV risk reduction, particularly for behavior that reduces risk through altering drug use behavior, but still leaves many users at risk. Intravenous drug users in the Netherlands and gays in the United States have organized around HIV-related issues with some success. Preliminary evidence from New York City suggests that organizing drug users may be an effective approach for achieving significant HIV risk reduction for individual users as well as those they associate with.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A neuropeptide precursor in cerebellum: proenkephalin exists in subpopulations of both neurons and astrocytes.

The adult rat cerebellum has minimal enkephalin immunoreactivity and is devoid of opiate-binding activity. Using novel monoclonal antibodies to the mammalian enkephalin precursor, we describe the immunofluorescent detection of proenkephalin, in the absence of mature enkephalin peptides, in subpopulations of rat cerebellar neurons and astrocytes. In cryostat sections, neurons that express proenkephalin include Golgi cells, macroneurons within deep cerebellar nuclei and a subpopulation of Purkinje cells. Proenkephalin messenger RNA and protein are present in subpopulations of both grey and white matter astrocytes, but not Bergmann glia. In dissociated glial culture, proenkephalin is expressed in process-bearing astrocytes, apparently in association with a subset of intermediate filaments. Proenkephalin within astrocytes is not seen until the second postnatal week and increases through to adulthood. Neuropeptide gene expression adds to the growing range of neuronal-type properties glial cells can display.

Animals↗
PubMed1990

Autosomal dominant rod-cone dysplasia in the Rdy cat. 1. Light and electron microscopic findings.

Detailed morphological analyses, including retinal layer thickness studies, were performed on heterozygous affected cats with autosomal dominant rod-cone dysplasia (gene symbol Rdy). Abnormalities were evident in retinas from the earliest age examined (2 weeks). Both rod and cone photoreceptors were affected equally by the dystrophy which was characterized by retarded and abnormal development of the visual cells. Photoreceptor inner segments remained rudimentary and outer segments did not elongate normally. Outer segment material was sparse and consisted mostly of whorls of disorganized and disoriented disc lamellae. Photoreceptor cell synaptic terminals showed delayed and incomplete synaptogenesis. Degenerative changes were first observed at 4.5 weeks of age and were characterized by the appearance of pyknotic nuclei in the outer nuclear layer and displacement of photoreceptor cells into the subretinal space. Degeneration began in central retinal regions and proceeded towards the periphery, resulting in progressive loss of the photoreceptor cell layers. By 30 weeks of age only two to five rows of nuclei remained in the outer nuclear layer. Area centralis degenerative lesions in advanced affected eyes were characterized by focal absence of the retinal pigment epithelium and choriocapillaris and thinning of the underlying tapetum. Retinal autoradiography showed that in normal kittens aged between 4.5 and 11 weeks of age rod outer segment renewal rates varied between 2.49 and 2.79 microns per 24 hr. The failure to form a labelled band in retinal autoradiograms from Rdy-affected kittens most probably indicates defective rod disc morphogenesis. It appears that the genetic defect in Rdy cats permits retarded development of the photoreceptor cells, but becomes lethal when these cells begin functional differentiation.

Animals↗
PubMed1990

Lens luxation in the dog and cat.

Dislocation, or luxation, of the lens arises as a result of rupture of the zonular fibers, which suspend the lens from the ciliary body. In the dog, lens luxation is most frequently encountered as a primary, heritable condition in which there appears to be an inherent weakness of the zonule. The condition is limited mainly to the Terrier breeds but has also been described in the Tibetan Terrier and Border Collie. The disease is essentially bilateral but seldom becomes apparent clinically before 3 or after 7 years of age. In most primary luxations, the lens passes into the anterior chamber and such cases must be regarded as emergencies on account of the likely development of secondary glaucoma; posterior luxations are usually less troublesome. Other causes of lens luxation include cataract formation, glaucoma, and uveitis. Congenital dislocations and those attributable to trauma alone are rare. In the cat, lens luxations are usually secondary and arise in later life.

Animals↗
PubMed1979

Genetic aspects of lens luxation in the Tibetan terrier.

Analyses were undertaken of 20 cases of lens luxation in British-bred Tibetan terriers, together with a further seven from Sweden. General proband segregation tests showed that the data were consistent with a simple autosomal recessive hypothesis (P = 0.152 +/- 0.0563). This was supported by high levels of inbreeding ranging from 0 to 24.3 per cent, with a mean of 14.3 per cent (SD 5.32 per cent). All affected cases traced back to one or more of three animals (born mid 1950s) on both sides of their pedigrees, all three being breed champions. Inclusion of data from repeat litters between presumed heterozygous animals gave a ratio of 25 lens luxation cases in 121 progeny, which again supported the same genetic theory. The age at onset (three to five years) mitigates against test mating of animals within the breed.

Animals↗