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Biomedical subjects

D H Anderson

Publications and source records attributed to D H Anderson.

At least 91 records · Page 5Linked to original sources

Anatomical recovery following retinal detachment: clinicopathological correlations.

The histological findings in experimental retinal detachment and reattachment of the cat retina are described. Loss of photoreceptor outer segments, mounding of the apical surface of the retinal pigment epithelium, and loss of the apical villi of the retinal pigment epithelium are prominent features of the detached cat retina. Reattachment within the first week of retinal detachment is followed by good photoreceptor regeneration and orientation. Longer term detachment of 2 to 6 weeks results in poorer photoreceptor outer segment regeneration and orientation 4 weeks following reattachment surgery. These experimental results are consistent with clinical data concerning visual recovery following retinal reattachment surgery.

Animals↗

The onset of pigment epithelial proliferation after retinal detachment.

The adult mammalian retinal pigment epithelium (RPE) is mitotically inactive, yet retains the capacity to proliferate under certain conditions. To determine the onset of RPE proliferation after retinal detachment, we examined experimentally detached cat retinas of 12, 24, 48, and 72 hr duration. An additional animal served as a nondetached, sham-operated control. 3H-thymidine was injected into the vitreous chamber and the eyes were processed for light microscopic autoradiography. Autoradiograms from both the control and the 12 hr detachment showed no evidence of labeled RPE nuclei; however, labeled nuclei were present at both 24 and 48 hr after detachment. Labeled nuclei per millimeter of RPE at 24 hr were 55% of the 48 hr rate. Mitotic figures were noted only at 48 and 72 hr after detachment. No labeled RPE nuclei appeared in autoradiograms that bordered the detachment zone. Electron micrographs showed that proliferating RPE cells assume several configurations, some of which have been reported in other species. The proliferative response of the RPE occurs much sooner than had previously been thought. It appears to be a local effect that does not involve retinal regions beyond the detachment boundaries, and it may have potentially adverse effects when the retina and RPE are reapposed after retinal reattachment surgery.

Animals↗

Disc morphogenesis in vertebrate photoreceptors.

Electron microscopic examination of the bases of adult rod and cone outer segments (rhesus monkey, ground squirrel, and grey squirrel) has led to a new model of disc morphogenesis. In this model the disc surfaces and disc rims develop by separate mechanisms and from separate regions of the membrane of the inner face of the cilium. This membrane is alternately specified into regions that will form either the disc surfaces or the disc rims. The disc surfaces develop by an evagination or outpouching of the ciliary membrane. The two surfaces of an evagination, scleral and vitreal, each form one of the surfaces of adjacent discs. The disc rim is initially specified as a region of ciliary membrane between adjacent disc-surface evaginations. This region grows bilaterally around the circumferences of adjacent discs, zippering together the apposed surfaces to form the rim and completed disc. At the same time it seals the plasma-membrane edges of the evaginations, which have become detached from the surfaces. Incisures form in rod discs by infolding of the rim and surfaces together, and they begin to form before the rim is completed around the disc perimeter. When a number of new discs are developing simultaneously the ciliary membrane at the base of an outer segment consists of a stack of rim forming and surface forming growth points. This model provides, in addition, for the continuous renewal of outer-segment plasma membrane. It also establishes a developmental basis for the structural uniqueness of the disc rim. Finally, it indicates an evolutionary relationship between the discs of vertebrate visual cells and the membrane specializations of invertebrate visual cells.

Animals↗

Rod photoreceptors and scotopic vision in ground aquirrels.

Ground squirrel retinas contain a relatively small complement of rods (5--10% of all photoreceptors) which are thought to provide the basis for a weak scotopic visual capacity. In a previous investigation of the California ground squirrel (Spermophilus beecheyi) involving the recording of a retinal gross potential, the electroretinogram (ERG), electrophysiological evidence for a viable scotopic signal could be obtained from some, but not all of the ground squirrels examined. To further pursue the possibility that there is a structural/functional discrepancy in the relationship between rod photoreceptors and scotopic vision in the ground squirrel, several experiments involving electrophysiological, behavioral, and anatomical observations have been conducted. We found that although about one-third of the ERGs recorded from a large sample of California ground squirrels lack those characteristics which would indicate the presence of a viable scotopic signal, the retinas of all the squirrels appear to contain the same small population of rod photoreceptors. Additional experiments on the golden-mantled ground squirrel (Spermophilus lateralis), including behavioral as well as ERG measurements and anatomical observations, lead to this same conclusion.

Animals↗

Mammalian cones: disc shedding, phagocytosis, and renewal.

During the past several years we have examined a variety of different mammalian retinas for ultrastructural evidence of cone disc shedding and RPE phagocytosis. In this paper we review our previously published evidence from squirrel and human retinas as well as present new evidence of cone disc shedding in rhesus monkey and cat. All these species show definitive evidence for the shedding of discs from cone outer segments and the phagocytosis of shed discs by apical processes of the RPE; both of these events closely resemble those described for mammalian rods. The occurrence of cone disc shedding leads directly to the conclusion that new membrane must be added to the cone outer segment in order to maintain its length. The successive evaginations, which are observed at the bases of cone outer segments, we consider to be indirect evidence for the addition of new discs. Finally, we propose a model for the structural organization of mammalian cone outer segments.

Animals↗

Scotopic and photopic vision in the California ground squirrel: physiological and anatomical evidence.

The California ground squirrel is a highly diurnal species previously thought to have an all-cone retina. This issue was re-examined in physiological and anatomical experiments. The electroretinogram (ERG) was used to measure the spectral sensitivity of the eye under different conditions of adaptation. The occurrence of a Purkinje shift could be demonstrated, although there was some indication that not all members of this species show such a shift. Spectral sensitivity of the dark-adapted eye of this squirrel is close to that predicted by a typical mammalian rhodopsin. Light adaptation produces a shift in spectral sensitivity to a peak location of about 525 nm. It was shown that two mechanisms having different spectral sensitivities contribute to the photopically recorded ERG. The degree to which these two mechanisms contribute to the ERG was found to be strikingly different from the degree to which the two contribute to visual behavior. Our anatomical results indicate that the retina of the California ground squirrel has two structurally distinct photoreceptors which, on the basis of various criteria, can be classified as cone and rod-like. The rod-like receptors comprise about 6-7% of the total. The two photoreceptor types differ in placement of their inner segments, size of their outer segments, outer segment ultrastructure, and terminal structure and organization.

Adaptation, Ocular↗

Disc shedding in rodlike and conelike photoreceptors of tree squirrels.

Electron microscopic observations suggest that the rodlike and conelike photoreceptors of diurnal tree squirrels shed outer segment discs. Twenty-four hours after injection of triated L-leucine, the rodlike photoreceptors show a band of radioactivity at the base of the outer segment. The conelike photoreceptor outer segments show only a pattern of diffuse labeling. These results strongly suggest that disc shedding can occur in photoreceptor outer segments in which proteins are diffusely renewed.

Animals↗

Pulmonary lesions due to opportunist mycobacteria. (Review includes 30 cases of M. kansasii infections).

The apparent increase in the incidence of opportunist mycobacterial pulmonary infection is assessed. The clinical, bacteriological and radiological characteristics of 34 cases of such infections seen over a period of ten years in Sheffield are reviewed. The typical radiological appearances consisting of cavities, fibrosis and opacities are described and illustrated. There has been in the past conflicting reports on the specificity of such radiological features; it is concluded that although such appearances are not pathognomonic, their presence should arouse suspicion of such an infection and this should be confirmed or refuted by bacteriological investigations.

Adult↗

Estimation and computation of the growth rate in Leslie's and Lotka's population models.

Leslie's or Lotka's population model has a rate of natural increase (lambda or r) which represents the growth rate of the population and characterizes the ability of the population to attain a stable age distribution. In this article are presented upper and lower bounds on that rate, primarily in terms of the net reproduction rate and other commonly used parameters of the population. Also a discussion is given of quadratically convergent numerical iterative methods of computing the growth rate.

Age Factors↗

Mutation of amino acids thought to polarize the oxaloacetate carbonyl in citrate synthase severely reduces but does not abolish activity of the enzyme.

Oligonucleotide-directed mutagenesis has been used to alter two active site residues of Escherichia coli citrate synthase, histidine-305 and arginine-314. Both residues are thought to be involved in the polarization of the carbonyl group of oxaloacetate and thus facilitate attack at the carbonyl carbon by acetyl-CoA. In one mutant, designated CS305H----A, His-305 was mutated to alanine and in the other, designated CS314R----L, Arg-314 was changed to leucine. Both mutants have greatly reduced turnover numbers, less than 0.1% of the wild-type value. The dissociation constant for formation of the binary enzyme-oxaloacetate complex, Ki, OAA, is at least 950 microM for CS305H----A, and about 500 microM for CS314R----L, 28 and 15 times the wild-type value, respectively. The Michaelis constants for the two substrates, KOAA and KAcCoA, which measure the affinity of the enzyme for the catalytically significant ternary complex, are less radically altered: values of KAcCoA are actually 3.5-fold and 4.6-fold lower for CS305H----A and CS314R----L, respectively. These kinetic effects are taken to mean that both His-305 and Arg-314 are important for the successful formation of an efficient transition state, very likely by polarizing the carbonyl group of oxaloacetate as has been suggested, and that the residual kinetic activity, in both mutants, occurs by a mechanism which benefits from only part of this polarization. Allosteric properties of the mutant enzymes, as measured by NADH inhibition and binding, and KCl activation, are normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗