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Biomedical subjects

G J Chader

Publications and source records attributed to G J Chader.

At least 199 records · Page 11Linked to original sources
PubMed1984

Choroideremia: a clinical, electron microscopic, and biochemical report.

An asymptomatic 19-year-old male with choroideremia had diffuse loss of retinal pigment epithelium (RPE) and choroid except for the periphery and macula. Fluorescein angiography of the arteriovenous phase showed absence of retinal pigment epithelium and exaggerated visualization of choroidal vessels in involved areas. The mother was a typical carrier with pigment stippling of the midperipheral retina. Histopathologic examination of affected areas of one eye showed marked degeneration of the outer and midretina with loss of retinal pigment epithelium and Bruch's membrane, absence of choriocapillaris, chorioretinal adhesions and gliosis. Atrophy of inner and mid-choroid was also observed. Pigmented macrophage-like cells had migrated into the outer and midretinal layers. Electron microscopy disclosed macrophage-like cells with trilaminar structures and photoreceptor phagosomes in the RPE and outer retina. Remnants of photoreceptor outer segments were adherent to the plasma membranes of the macrophage-like cells. Biochemical analysis of retinal tissue samples for interphotoreceptor retinoid-binding protein (IRBP) showed marked reduction in the 146K bands in the equator and posterior pole in the patient compared to controls. Cyclic nucleotide content was altered in the retinal equator. Cyclic AMP was several-fold higher in the RPE-choroid complex of the affected eye than in the control.

Adult↗
PubMed1984

Effects of diamide on cyclic nucleotide levels in rat retina.

The concentrations of guanosine 3',5' monophosphate (cyclic GMP) and adenosine 3',5' monophosphate (cyclic AMP) were measured in rat retinas incubated under control conditions and in retinas incubated with diamide, a relatively specific glutathione oxidant. Retinas incubated with either glucose or pyruvate as the substrate for 30 min in the dark contained about 50 picomoles cyclic GMP/mg protein and 7 picomoles cyclic AMP/mg protein. Light-exposed control retinas contained about 70% less cyclic GMP (14.4 picomoles/mg protein) and 20% less cyclic AMP (5.4 picomoles/mg protein). Addition of diamide to the incubation medium at concentrations between 0.1 and 1.0 mM produced a concentration-dependent decrease in the dark level of cyclic GMP, but did not affect its concentration in the light or the concentration of cyclic AMP in dark-maintained and light-exposed retinas. The major effect of diamide was to reduce the normal dark-light difference in the concentration of cyclic GMP. Oxidizing conditions thus appear to alter selectively the light-sensitive compartment of retinal cyclic GMP.

Animals↗
PubMed1984

Effects of butyrate, retinol, and retinoic acid on human Y-79 retinoblastoma cells growing in monolayer cultures.

The effects of butyrate, retinol, and retinoic acid were tested on growth and differentiation of human Y-79 retinoblastoma cells in monolayer cultures. Treatment with 4 mM butyrate resulted in marked growth inhibition of cells, due mostly to increased death rate. The effect was greater in serum-supported cultures in which the proliferation rate was high and the effect was less in the serum-free, defined medium in which the cells were differentiated and the growth rate was slow, suggesting a cell-cycle-specific action of this substance. Moreover, butyrate induced morphologic changes in the viable cells; these changes consisted of an elongated appearance of the cells and of retraction of long processes formed in the serum-free-supported cultures. Retinol at 20 microM also affected the cell viability both in serum-containing and in serum-free culture medium. Retinoic acid at 50 microM induced reversible growth inhibition of cells growing in serum-containing medium and cell death in the defined medium-supported cultures. Combination of 0.5 mM butyrate with 50 microM retinoic acid resulted in an enhanced inhibition of growth in an apparently synergistic fashion. These results demonstrated that butyrate, retinol, and retinoic acid suppressed Y-79 cell growth in vitro and could be useful in future studies of these compounds in retinoblastoma tumors in vivo.

Butyrates↗
PubMed1983

Chick retinal pigment epithelium. A new culture system for studying H2-histamine receptors.

Histamine elevates the intracellular cyclic AMP levels in cultured embryonic chick retinal pigment epithelium. The half-maximal activity is 6 X 10(-6) M. The effect of histamine is mediated by H2 receptors, i.e., inhibited by the H2 antagonist cimetidine and not affected by the H1 antagonists diphenhydramine and pyrilamine. The inhibition constant (KI) of cimetidine is 1.3 X 10(-8) M. Thus, the present system offers the opportunity of studying the nature of coupling between histamine receptors and adenylate cyclase under controlled conditions in a homogeneous cell type.

Animals↗
PubMed1982

Interphotoreceptor retinol-binding proteins: possible transport vehicles between compartments of the retina.

In the eye, vitamin A (retinol) is mainly stored in the retinal pigment epithelium(RPE) although its primary function is in the visual process in the photoreceptor organelles of the neural retina (NR). It is well established that during light adaptation, the amount of retinol drops in the NR but rises in the RPE. During dark adaptation, the converse occurs. This indicates a migration of retinoid between the two tissues, the direction of which is dictated by the state of light or dark adaptation of the photoreceptors. The mechanism by which this migration is effected is unknown. We now present evidence that at least one protein exists in the subretinal space or on the cell surfaces which demonstrates many of the unique characteristics one would expect of an interphotoreceptor retinol-binding protein and could function as a vitamin A transport vehicle between NR and RPE.

Adaptation, Ocular↗
PubMed1982

Tissue culture of chick embryonic choroidal cells: cell aggregation and pigment accumulation.

Cells originating from the chick embryo choroid were grown in culture for up to 1 month. The cells did not form coherent monolayer colonies but rather formed large transparent cell aggregates surrounded by a random, loose network of cells. The cell aggregates avidly took up and retained pigment granules while the individual cells did not. Choroidal cell aggregates were not similar to the "lentoid" bodies described by Okada and coworkers in cultures from other ocular tissues; they did not develop fiber cells and did not synthesize delta-crystallin. Thus aggregation of ocular cells appears to be a necessary but insufficient step for the formation of a "lentoid" body.

Animals↗
PubMed1982

Retinal pigment epithelium contains a distinctive strychnine-binding site.

Membranes prepared from the retinal pigment epithelium of several species possess a specific site which binds [3H]strychnine. This binding has a somewhat lower affinity and a much greater density than the corresponding interaction in the hindbrain or neural retina. Binding is not greatly altered in the presence of 10(-3) M glycine, L-alanine, beta-alanine, taurine, or serine. Thus, the receptor does not resemble the classical glycine receptor of the hindbrain and spinal cord. This new type of binding site appears to be confined to the pigment epithelial layer of the retina.

Amino Acids↗
PubMed1982

Induction of dark-adaptive retinomotor movement (cell elongation) in teleost retinal cones by cyclic adenosine 3','5-monophosphate.

In the teleost retina, the photoreceptors and retinal pigment epithelium (RPE) undergo extensive movements (called retinomotor movements) in response to changes in light conditions and to an endogenous circadian rhythm. Photoreceptor movements serve to reposition the light-receptive outer segments and are effected by changes in inner segment length. Melanin granule movements within the RPE cells provide a movable melanin screen for rod outer segments. In the dark (night), cones elongate, rods contract, and pigment granules aggregate to the base of the RPE cell; in the light (day), these movements are reversed. We report here that treatments that elevate cytoplasmic cyclic adenosine 3',5'-monophosphate (cAMP) provoke retinomotor movements characteristic of nighttime dark adaptation, even in bright light at midday. To illustrate this response, we present a quantitative description of the effects of cyclic nucleotides on cone length in the green sunfish, Lepomis cyanellus. Cone elongation is induced when light-adapted retinas are exposed to exogenous cAMP analogues accompanied by phosphodiesterase (PDE) inhibitors (either by intraocular injection or in retinal organ culture). Cone movements is not affected by cyclic GMP analogies. Dose-response studies indicate that the extent, but not the rate, of cone elongation is proportional to the concentration of exogenous cAMP and analogue presented. As has been reported for other species, we find that levels of cAMP are significantly higher in dark- than in light-adapted green sunfish retinas. On the basis of these observations, we suggest that cAMP plays a role in the light and circadian regulation of teleost cone length.

Animals↗
PubMed1982

In vitro studies on shedding and phagocytosis of rod outer segments in the rat retina: effect of oxygen concentration.

The processes of outer segment shedding and phagocytosis were found to be significantly enhanced in explants of rat retina and pigment epithelium (PE) newly placed in culture. The number of phagosomes reached a maximum at 2 hr of incubation and then rapidly decreased, as is observed in rats entrained in a normal light-dark schedule when the lights are turned on in the morning. This pattern was not qualitatively affected by the time of day the tissues were excised or by the presence of a high concentration of melatonin in the culture medium. The shedding peak in vitro was observed only when the retina-PE unit was incubated in an atmosphere composed of 45% oxygen, 5% CO2, and 50% air. When the atmosphere contained lower (95% air and 5% CO2) or higher (95% O2 and 5% CO2) oxygen, PE cells contained only a few scattered phagosomes. These functional differences may be caused by different arrangement of PE cell microvilli at a "moderate" (45%) O2 concentration vs. "low" or "high" O2 concentrations. A balanced O2 level thus appears to be critical for phagocytosis in explant culture.

Animals↗
PubMed1981

Pigment epithelial cells in culture. Metabolic pathways required for phagocytosis.

The phagocytosis of bovine rod outer segments as measured by the uptake of 3H-labeled outer segments was studied in a culture system. Phagocytosis was markedly inhibited by the lack of glucose and by two inhibitors of the tricarboxylic acid cycle-cytochrome system, dinitrophenol and malonate. Lactate production was increased in phagocytizing cells, but the hexose monophosphate shunt was not stimulated. The data support the conclusion that the tricarboxylic acid cycle and its associated cytochrome system play an important role as an energy source for phagocytosis in these cells. Compromise of this energy source rapidly leads to a suppression of the phagocytic process.

Animals↗
PubMed1980

Differential control of protein kinase activities of the retinal photoreceptor. Cation effects on phosphorylation by adenosine and guanosine 5'-triphosphates.

ATP-kinase activity in photoreceptor membranes is maximal at equimolar amounts of ATP and Mg2+. GTP-kinase activity is maximal with high concentrations of Mn2+. Under these conditions, calcium ion markedly inhibits phosphorylation with ATP but not with GTP. GTP-kinase activity is maximal at pH 6.5 and decreases at higher pH; little change is seen in ATP-kinase activity over the pH range of 6.0-7.5. GTP-kinase activity is inhibited by ATP and other adenine compounds; ATP-kinase activity is less sensitive, although I mM adenosine decreases activity by about threefold. No marked differences in the protein moieties phosphorylated by ATP or GTP were seen in bovine or frog outer segment membranes. Fluxes in cation and metabolite concentrations as well as availability of ATP and GTP could thus exert a major influence on protein kinase activity in the photoreceptor unit, affording the possibility of differential phosphorylation under various physiological conditions.

Adenosine↗
PubMed1980

Cyclic nucleotides vary by area in the retina and pigmented epithelium of the human and monkey.

Cyclic GMP and cyclic AMP are present in lower concentrations in the central (macular) region of the neural retina of the human and monkey than in other areas. This pattern approximates the distribution of rod photoreceptor cells. Surprisingly, an inverse gradient of cyclic GMP concentration is observed in the pigmented epithelium. Levels in the central region are over fourfold higher than in cells in the periphery, offering the first evidence of biochemical differences in this embryologically uniform cell type.

Adolescent↗