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R G Foster

Publications and source records attributed to R G Foster.

At least 55 records · Page 3Linked to original sources
PubMed1997

Retinoblastoma protein-dependent growth signal conflict and caspase activity are required for protein kinase C-signaled apoptosis of prostate epithelial cells.

Both protein kinase C and the retinoblastoma tumor suppressor protein have been linked to the regulation of cell growth and cell death, suggesting the differential roles these factors play in mediating cell fate. In some cells, protein kinase C-induced activation of the retinoblastoma protein results in G1 arrest. However, inducible overexpression and activation of the protein kinase Calpha isozyme or the addition of 12-O-tetradecanoylphorbol-13-acetate in the prostate epithelial cell line, LNCaP, resulted in apoptosis preceded by induction of p21 and dephosphorylation of the retinoblastoma protein. Consistent with a role for the retinoblastoma growth suppressor protein in protein kinase C-induced apoptosis, DU145 cells, which do not express functional retinoblastoma protein or LNCaP cells, which have been transfected with the retinoblastoma inhibitor, E1a, were resistant to apoptosis. LNCaP apoptosis was initiated by a unique conflict between the growth-suppressive activity of the retinoblastoma protein and growth-promoting mitogenic signals. Thus, when this conflict was prevented by serum depletion, apoptosis was suppressed. The caspase family of cysteine proteases is believed to encompass the execution machinery of mammalian apoptosis, and addition of the cell-permeable caspase inhibitor, Z-Val-Ala-Asp-fluoromethylketone, afforded nearly total protection from protein kinase C-signaled apoptosis. This protection correlated with the total loss of caspase activity as measured by the proteolytic cleavage of nuclear poly(ADP-ribose) polymerase. On the basis of these results, we propose that protein kinase C regulates a novel cell death pathway that is initiated by a cellular conflict between retinoblastoma growth-suppressive signals and serum mitogenic signals in proliferating prostate epithelial cells and that is executed by the caspase family of cysteine proteases.

Adenovirus E1A Proteins↗
PubMed1997

A novel and ancient vertebrate opsin.

We describe the identification of a novel opsin gene isolated from the eyes of Atlantic salmon. The cDNA sequence predicts a protein that has the key features of an opsin, but shows only 32-42% amino acid identity to the known opsin families. Phylogenetic analysis suggests that this opsin is a member of a hitherto unrecognised opsin family that diverged early in the evolution of vertebrate photopigments. We have tentatively called this opsin family the vertebrate ancient (VA) opsins. The identification of VA opsin may ultimately help to resolve some of the uncharacterised photoreceptor functions of the eye, which include the regulation of circadian rhythms, pupil size and corneal pigmentation.

Amino Acid Sequence↗
PubMed1997

Cell anchorage regulates apoptosis through the retinoblastoma tumor suppressor/E2F pathway.

Epithelial cells are dependent upon adhesion to extracellular matrix for survival. We show that loss of beta1 integrin receptor contact with extracellular matrix signals the inhibition of G1 cyclin-dependent kinase activity. This loss of cyclin-dependent kinase activity leads to accumulation of the hypophosphorylated (active) form of the retinoblastoma tumor suppressor protein (Rb). We present evidence that in epithelial cells deprived of matrix contact, the growth suppression signal elicited by hypophosphorylated Rb opposes stimulatory signals from serum growth factors, leading to a cell cycle conflict that triggers apoptosis. This apoptotic pathway is modulated by Bcl-2 through a novel mechanism that regulates Rb phosphorylation. We present evidence that the Rb-dependent apoptotic pathway functions in vivo in the apoptosis of the prostate glandular epithelium following castration.

Animals↗
PubMed1997

Opsin-like immunoreactivity in the circadian pacemaker neurons and photoreceptors of the eye of the opisthobranch mollusc Bulla gouldiana.

Circadian pacemaker cells in the eyes of the opisthobranch mollusc Bulla gouldiana generate a near 24-h rhythm in the frequency of optic nerve impulses. Previous electrophysiological studies suggest that these basal retinal neurons are intrinsically photosensitive and transduce light signals that shift the phase of their pacemaker mechanism. To test whether the pacemaker neurons contain opsin-like proteins, several polyclonal antibodies that recognize opsins of vertebrate photoreceptors have been tested on histological sections of the eye and on the neurons in primary cell culture. The antibodies label both the pacemaker cells and the large distal photoreceptors that surround the lens. Immunoblot analyses of the proteins of the eye have identified a single band at 62+/-4 kDa. These opsin antibodies may label the photopigment used in the entrainment of the circadian pacemaker.

Animals↗
PubMed1997

An immunocytochemical study of encephalic photoreceptors in three species of lamprey.

The extraretinal and extrapineal photoreceptors of three species of adult lamprey, sea lamprey (Petromyzon marinus), river lamprey (Lampetra fluviatilis) and silver lamprey (Ichthyomyzon unicuspis) were studied using antibodies raised against photoreceptor rod and cone opsins, alpha-transducin and arrestin. In all three species cells in the pineal organ (P), parapineal organ (PP), nucleus preopticus (T5), nucleus commissurae postopticae (D8), nucleus ventralis hypothalami (D10) and nucleus dorsalis hypothalami (D11) were labelled by one or more of the anti-opsin antibodies. In addition, anti-arrestin antibodies labelled cells within the D8 and anti-alpha-transducin antibodies labelled cells within the pineal complex and hypothalamus (primarily D8 and/or D10). A more variable and species dependent pattern of opsin, arrestin and alpha-transducin labelling was observed within the nucleus commissurae postinfundibularis (D12) in an area comprising the nucleus dorsalis thalami pars subhabenularis (D4sh) and nucleus dorsalis thalami pars caudalis/nucleus commissurae posterioris (D4c/M1), and in the proximity of the second Müller cells in the ventrocaudal diencephalon (2.MZ/M6). The majority of the neurons labelled within the pineal and parapineal organs and hypothalamus were periventricular with clear cerebrospinal fluid contacts (CSF-contacting neurons). Labelled neurons in the epithalamic (D4sh and D4c/M1) and caudal diencephalon (2.MZ/M6) had no obvious ventricular contacts. We speculate that the "primitive" vertebrate brain of lampreys represents an ancestral condition in which different populations of encephalic photoreceptors are associated with different behavioural and physiological responses. Image-forming vision needs an eye, but irradiance detection does not require a specialised organ. Rather the photoreceptors could be closely associated with their effector systems within the brain.

Animals↗
PubMed1996

Light perception in the vertebrate brain: an ultrastructural analysis of opsin- and vasoactive intestinal polypeptide-immunoreactive neurons in iguanid lizards.

Recent biochemical and immunocytochemical evidence indicates that a population of circadian and reproductive rhythm-entraining photoreceptors lies in the basal diencephalon of iguanid lizards. Here, we report the results of correlated light and electron microscopy of opsin-immunoreactive cells in the basal brain, and we discuss their ultrastructural relationship to known photoreceptors. Cerebrospinal fluid (CSF)-contacting bipolar neurons in the lizards Anolis carolinensis and Iguana iguana were immunolabeled with antisera generated against vertebrate retinal opsins and vasoactive intestinal polypeptide (VIP). Within the brain, opsin-immunoreactive cells were found exclusively in the ependyma of the basal region of the lateral ventricles (adjacent to nucleus paraolfactorius/nucleus ventromedialis and neostriatum/paleostriatum). Cells in the same anatomical location and with the same morphology were labeled with anti-VIP antisera. These cells possessed a dendritic process that extended toward the lateral ventricle, ending in a bulbous terminal that protruded into the ventricle. Axonal processes travelled ventrally and caudally. The entire cell, including the axonal process, exhibited opsin-like and VIP-like immunoreactivity. By light microscopy, opsin-like immunostaining appeared punctate, with immunoreactivity greatest in the bulbous terminal. Opsin- and VIP-immunostained thick sections were resectioned, and individual cells observed by light microscopy were then characterized using electron microscopy. We found that all immunostained cells were morphologically similar and that they were morphologically distinct from neighboring nonimmunoreactive cells. CSF-contacting opsin- and VIP-immunoreactive cells lacked the membranous stacks characteristic of retinal photoreceptors but were ciliated and contained numerous large electron-dense vesicles. Multiple synaptic contacts were made on the soma and putative dendritic processes of opsin- and VIP-immunoreactive CSF-contacting neurons. Our results provide the first ultrastructural characterization of opsin-immunostained encephalic CSF-contacting neurons in a vertebrate animal, and they indicate that these putative photoreceptors share structural features with pineal photoreceptors and with certain invertebrate extraretinal photoreceptors, but they are morphologically and biochemically distinct from visual photoreceptors of the retina.

Animals↗
PubMed1996

The spatio-temporal pattern of photoreceptor degeneration in the aged rd/rd mouse retina.

Photoreceptor degeneration in the retina of the rd/rd (retinal degeneration) mice has been studied using immunocytochemistry with antisera against cone- and rod-opsin. The rd/rd mice exhibited different regional specific rates of degeneration for rods and cones. As early as postnatal day 25, cells labelled with the rod-opsin and cone-opsin antisera disappeared preferently from the central retina. Whereas in the inferior half of the retina, degeneration subsequently proceeded towards the periphery, this did not occur in the dorsal hemisphere. By the age of 100 days, many cells immunoreactive for the cone-opsin antiserum and a few cells immunoreactive for the rod-opsin antiserum were located in an area of the dorsal retina. The ventral retina lacked labelled elements at this age. Finally, rd/rd mice at one year or 600 days of age contained a similar number of cone-opsin immunopositive cells (approximately 2000-2800 cells), occupying almost the same area in the retina as that found at 100 days of age. A photoreceptor candidate for the entrainment of non-visual photoreception probably remains in the cone population in aged rd/rd mice.

Aging↗
PubMed1995

Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics.

In this report we have characterized the photopigments mediating circadian phase shifts in retinal degenerate (rd) mice. In aged rd/rd mice, which lack detectable opsin, high performance liquid chromatography (HPLC) was used to quantify the photopigment chromophore 11-cis-retinaldehyde. This chromophore was photoisomerized in whole eyes, suggesting the presence of a functional opsin-based photopigment system. We also analyzed the spectral sensitivity of phase shifting circadian locomotor rhythms. Our data implicate a photopigment that is consistent with the involvement of the middle wavelength-sensitive cone photoreceptors (M-cones; lambda(max) = 511 nm) found in the mouse retina. In addition, discrete near-ultraviolet (UV-A) pulses were capable of eliciting large phase shifts in circadian locomotor activity rhythms. This result is consistent with the involvement of the short wavelength-sensitive cone photoreceptors (UV-cones; lambda(max) = 359 nm) in photoentrainment. Collectively, these data suggest that both cone classes of the mouse may mediate the photic regulation of circadian rhythms. If this is the case, circadian sensitivity can be maintained by very few degenerate cones. Alternatively, an unknown class of ocular photoreceptor may fulfill this function.

Animals↗
PubMed1995

The persistence of cone photoreceptors within the dorsal retina of aged retinally degenerate mice (rd/rd): implications for circadian organization.

Rod- and cone-opsin specific antibodies were used in an attempt to immunolabel remaining photoreceptor cells in the mutant rd (retinal degeneration) mouse retina. We identified a region-specific distribution in the pattern of photoreceptor degeneration, with the dorsal retina showing markedly less photoreceptor degeneration than the ventral retina. All rod and cone immunoreactive cells disappeared in the ventral retina by 100-120 days of age. By contrast, both cone and a small number of rod immunopositive cells were identified in the dorsal retina at this time. By 200 days all rod immunoreactive cells had disappeared. At 360 days numerous cone immunoreactive cells remained within a restricted region of the dorsal retina. As rd mice show unattenuated circadian responses to light, these remaining photoreceptor cells within the dorsal retina become candidates for the regulation of circadian physiology by light.

Age Factors↗
PubMed1994

Replication of an osteopetrosis-inducing avian leukosis virus in fibroblasts, osteoblasts, and osteopetrotic bone.

Avian leukosis virus (ALV)-induced osteopetrosis is caused by the abnormal growth and differentiation of osteoblasts. To evaluate the role of infection in osteopetrosis induction, the replication of an osteopetrosis-inducing virus (Br21) has been compared in osteopetrotic bone, calvarial-derived osteoblasts, and chick embryo fibroblasts. Much higher levels of infection occurred in diseased bone than in the cultures. Severe cases of osteopetrosis contained 10 times more viral DNA, 30 times more mature capsid protein, 5 to 10 times more Gag precursor protein, and 2 to 3 times more Env protein than the infected cultures. Virus replication in the cultured osteoblasts was similar to that in fibroblasts except for a distinctive asymmetric localization of Gag proteins. In osteopetrotic chickens, bones became atypically enlarged and sera contained elevated levels of osteoblast differentiation markers (alkaline phosphatase and osteocalcin). In cultures, infections did not affect the growth or differentiation of osteoblasts. Thus, the infected cultures lacked aspects of the bone environment that support both the high levels of infection and the aberrant function of osteoblasts characteristic of ALV-induced osteopetrosis.

Animals↗
PubMed1994

Establishment of interference in osteoblasts by an osteopetrosis-inducing avian leukosis virus.

Avian leukosis virus (ALV)-induced osteopetrosis is characterized by the presence of unintegrated viral DNA is diseased bone. To learn more about this phenomenon, ALVs with high (Br21) and low (RAV-1) osteopetrotic potential have been compared for the ability to establish superinfection resistance in cultures of calvarial-derived osteoblasts. Both viruses could establish interference in osteoblast cultures that were maintained as growing cells. This interference was maintained when cultures were induced to differentiate. These results suggest that the unintegrated viral DNA in osteopetrotic bone is not due to the inability of osteopetrosis-inducing viruses to establish superinfection resistance in osteoblasts.

Animals↗
PubMed1994

Visual and circadian responses to light in aged retinally degenerate mice.

The progression of photoreceptor degeneration in retinally degenerate (rd) mice commences early in postnatal development resulting in the complete loss of rods by 60-70 days of age followed by the more protracted loss of cones. We have previously shown that rd mice 80 days of age are capable of phase shifting their circadian locomotor rhythms in response to brief pulses of light and these animals show the same sensitivity as wild-type (+/+) controls. If surviving cones mediate these circadian responses, then one would expect the sensitivity of the circadian system in rd mice to decline with age and parallel the loss of cones. We demonstrate that aging rd mice (80-767 days of age) remain capable of photically regulating circadian locomotor rhythms in a manner indistinguishable from +/+ mice. Circadian responses to light do not parallel cone cell degeneration in rd mice. In contrast to the circadian responses to light, old (> 210 days of age) rd mice show no visually-evoked behavioral or electroretinogram (ERG) responses.

Aging↗
PubMed1994

Identification of vertebrate deep brain photoreceptors.

Since the beginning of this century evidence has accumulated which demonstrates that nonmammalian vertebrates possess photoreceptors situated deep within the brain. These photoreceptors have been implicated in several different areas of physiology, but in all species examined, they play a critical role in the regulation of circadian and reproductive responses to light. Many attempts have been made to localize these sensory cells over the past 50 years, but until recently all attempts have failed. As a result, this important sensory system remains largely unexplored. Recent attempts to localize these photoreceptors, in a range of vertebrates, using combined antibody and biochemical approaches has met with some success. However, inconsistencies have emerged. Published and preliminary data raise the possibility of several types of encephalic photoreceptor photopigment (cone-like, rod-like or different from both), and depending on species at least two types of photoreceptor cell: CSF-contacting neurons (larval lamprey, reptiles and birds) and classical neurosecretory neurons within the nucleus magnocellularis preopticus (NMPO)(fish and amphibians).

Animals↗
PubMed1993

Vitamin A2-based photopigments within the pineal gland of a fully terrestrial vertebrate.

Fully terrestrial vertebrates were previously thought to exclusively employ vitamin A1 to generate visual pigments. However, recent studies on the visual system of the lizard Anolis carolinensis have shown that its visual pigments are vitamin A2-based. This unexpected result prompted an investigation of the pineal photopigments in this species [13]. HPLC analysis has shown that this extraretinal photoreceptor also exclusively utilizes a vitamin A2-derived chromophore. The adaptive significance of this chromophore within the pineal is unclear. The extended long wavelength sensitivity characteristic of vitamin A2-based visual pigment systems may enhance important visual tasks such as prey detection or mate selection [13]. A similar argument cannot be made for the pineal, whose role is not image formation, but rather detection of the irradiance changes associated with dawn and dusk. We suggest that the pineal may passively utilize whatever retinoids have been adaptively selected by the visual system.

Adaptation, Physiological↗
PubMed1993

Differential expression of interphotoreceptor retinoid-binding protein, opsin, cellular retinaldehyde-binding protein, and basic fibroblastic growth factor.

The mRNA for rat interphotoreceptor retinoid-binding protein (IRBP) consists of 5.2 kb and 6.4 kb transcripts which are expressed early during retinal development. Here, we characterized rat IRBP cDNA and genomic clones, determined the mechanism generating the two transcripts and compared their expression to mRNAs for opsin, cellular retinaldehyde-binding protein (CRAlBP) and basic fibroblast growth factor (bFGF). We found that human and rat IRBPs have a high degree of sequence homology (86% amino acid identity over the fourth repeat). RNA-PCR studies and Northern blot analysis, showed that the 6.4 kb mRNA has a longer 3'-untranslated region (UTR) than the 5.2 kb message. Both IRBP transcripts, but not the mRNA for opsin are present in the neonatal and adult pineal. During development, the mRNAs for IRBP and opsin reach one-half of their maximal levels by P5 and P11, respectively. The ratio of the two IRBP mRNAs remains constant throughout life. In contrast, the ratio of the longest to the shortest opsin mRNA decreases between E19 and 1 year of age. Immunohistochemistry demonstrated a marked increase in the amount of IRBP in the interphotoreceptor matrix between P1 and P9 corresponding to the enhanced expression of this mRNA. Up-regulation of opsin mRNA expression during the second postnatal week corresponds to the emergence of the outer segments. The temporal expression of CRAlBP is similar to IRBP while bFGF is not expressed until after photoreceptor differentiation is complete. In summary, two 3'-transcription termination sites explain the difference in IRBP mRNA sizes. The different temporal and tissue specific patterns of IRBP and opsin expression suggest that separate mechanisms control the expression of these two genes. The expression patterns of IRBP and CRAlBP are consistent with the role of vitamin A as a morphogen and bFGF in neuronal maintenance.

Age Factors↗
PubMed1993

Stent placement in a splenic vein stenosis after TIPS creation.

A hemodynamically significant splenic vein stenosis was found during placement of a transjugular intrahepatic portosystemic shunt in a patient with gastric variceal bleeding. A second stent was placed across the splenic vein stenosis, which was obstructing normal hepatopetal flow, causing venous hypertension in the splenic and short gastric veins. This produced a successful hemodynamic and angiographic result and, clinically, controlled the patient's bleeding.

Constriction, Pathologic↗
PubMed1993

Photoreceptors regulating circadian behavior: a mouse model.

Our recent studies have examined circadian photoreception in mice with hereditary retinal disorders (rd/rd and rds/rds). Despite the loss of visual function in these mice, circadian responses to light remain unaffected. Using c-fos expression within the suprachiasmatic nuclei (SCN) as a marker of neural activation of the circadian entrainment pathway, we have found identical levels of Fos in the SCN of rd/rd and +/+ mice in response to retinal illumination. On the basis of action spectrum studies, and measurements of photopigment retinoids using high-pressure liquid chromatography, we believe that the photopigment mediating circadian responses to light is based upon an opsin, and that 11-cis-retinaldehyde is the photopigment chromophore. Preliminary measurements of mouse rod opsin, blue cone, and green-red cone opsin messenger RNA in retinally degenerate mice suggest that none of these opsins is exclusively used to mediate circadian responses to light. Collectively, our data suggest that circadian photoreception can be maintained by a very small number of rod or cone cells without outer segments, or, alternatively, is performed by an unrecognized class of photoreceptive cell within the mammalian retina.

Animals↗