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F Gonzalez-Fernandez

Publications and source records attributed to F Gonzalez-Fernandez.

33 records · Page 2Linked to original sources
PubMed1993

Differential expression of retinal proteins in a pineal parenchymal tumor.

The pineal gland and retina share histogenetic features that reflect a similar neurosensory/photosensory ontogeny. Pineal parenchymal tumors demonstrate a highly variable and incomplete photosensory differentiation evidenced by specific cytoarchitectural features and the expression of photosensory retinal S-Antigen (S-Ag). Despite these neuro-ontogenetic parallels, pineal parenchymal tumors have not been well studied for the neuroretinal phenotypes that accompany normal neuroretinal development. The investigation of photoreceptor gene expression may provide an important insight into the histogenesis of pineal parenchymal neoplasms. In this study, a pineal parenchymal tumor of the "mixed pineoblastoma/pineocytoma" type was examined for the expression of several photoreceptor, glial and neuronal proteins including: interphotoreceptor retinoid-binding protein (IRBP), rod opsin, cone opsin, S-Ag and cellular retinaldehyde-binding protein (CRA1BP). The detection of IRBP and its mRNA, the earliest photoreceptor-associated protein expressed during retinal development, corroborated the rudimentary photosensory differentiation of this tumor which had limited cytoarchitectural evidence for pineal differentiation. The analysis of IRBP expression may facilitate the diagnostic recognition of primitive pineal neoplasms and further define the neuroretinal differentiation which occurs in pineal parenchymal tumors.

Adolescent↗
PubMed1993

Interphotoreceptor retinoid-binding protein (IRBP), a major 124 kDa glycoprotein in the interphotoreceptor matrix of Xenopus laevis. Characterization, molecular cloning and biosynthesis.

We have demonstrated that the neural retina of Xenopus laevis secretes into the extracellular matrix surrounding the inner and outer segments of its photoreceptors a glycoprotein containing hydrophobic domains conserved in mammalian interphotoreceptor retinoid-binding proteins (IRBPs). The soluble extract of the interphotoreceptor matrix contains a 124 kDa protein that cross-reacts with anti-bovine IRBP immunoglobulins. In vitro [3H]fucose incorporation studies combined with in vivo light and electron microscopic autoradiographic analysis, showed that the IRBP-like glycoprotein is synthesized by the neural retina and secreted into the interphotoreceptor matrix. A 1.2 kb Xenopus IRBP cDNA was isolated by screening a stage 42 (swimming tadpole) lambda Zap II library with a human IRBP cDNA under low-stringency conditions. The cDNA hybridizes with a 4.2 kb mRNA in adult Xenopus neural retina, tadpole heads as well as a less-abundant mRNA of the same size in brain. During development, IRBP and opsin mRNA expression correlates with photoreceptor differentiation. The translated amino acid sequence of the Xenopus IRBP clone has an overall 70% identity with the fourth repeat of the human protein. Sequence alignment with the four repeats of human IRBP showed three highly conserved regions, rich in hydrophobic residues. This focal conservation predicts domains important to the protein's function, which presumably is to facilitate the exchange of 11-cis retinal and all-trans retinol between the pigment epithelium and photoreceptors, and to the transport of fatty acids through the hydrophilic interphotoreceptor matrix.

Amino Acid Sequence↗
PubMed1993

Identification of novel rhodopsin mutations responsible for retinitis pigmentosa: implications for the structure and function of rhodopsin.

Ten rhodopsin mutations have been found in a screen of 282 subjects with retinitis pigmentosa (RP), 76 subjects with Leber congenital amaurosis, and 3 subjects with congenital stationary night blindness. Eight of these mutations (gly51-to-ala, val104-to-ile, gly106-to-arg, arg135-to-gly, cys140-to-ser, gly188-to-glu, val209-to-met, and his211-to-arg) produce amino acid substitutions, one (gln64-to-ter) introduces a stop codon, and one changes a guanosine in the intron 4 consensus splice donor sequence to thymidine. Cosegregation of RP with gln64-to-ter, gly106-to-arg, arg135-to-gly, cys140-to-ser, gly188-to-glu, his211-to-arg, and the splice site guanosine-to-thymidine indicates that these mutations are likely to cause retinal disease. Val104-to-ile does not cosegregate and is therefore unlikely to be related to retinal disease. The relevance of gly51-to-ala and val209-to-met remains to be determined. The finding of gln64-to-ter in a family with autosomal dominant RP is in contrast to a recent report of a recessive disease phenotype associated with the rhodopsin mutation glu249-to-ter. In the present screen, all of the mutations that cosegregate with retinal disease were found among patients with RP. The mutations described here bring to 35 the total number of amino acid substitutions identified thus far in rhodopsin that are associated with RP. The distribution of the substitutions along the polypeptide chain is significantly nonrandom: 63% of the substitutions involve those 19% of amino acids that are identical among vertebrate visual pigments sequenced to date.

Alleles↗
PubMed1992

Ciliary body adenoma in a 10-year-old girl who had a rhabdomyosarcoma.

A retrolenticular fibrovascular membrane occurred in the setting of a ciliary body mass in a 10-year-old black girl who had been successfully treated for a rhabdomyosarcoma of the lung. The results of a transscleral biopsy of the mass demonstrated it to be a pigmented adenoma of the ciliary body. A lensectomy and membranectomy were performed to aid in the follow-up and rehabilitation of the eye. At 9 months after surgery, the patient had 20/25 vision with no evidence of tumor growth. This case demonstrates an unusual cause of cyclitic membrane formation and suggests that transscleral biopsy may be a useful adjunct in the management of selected ciliary body masses.

Adenoma↗
PubMed1992

Expression of developmentally defined retinal phenotypes in the histogenesis of retinoblastoma.

Retinoblastoma, the most common intraocular tumor of childhood, is a malignant neoplasm that arises during retinal development. The embryonal cell target for neoplastic transformation is not yet clearly defined. To better understand the histogenetic potential of this tumor, the expression of photoreceptor and glial cell-associated proteins were examined in 22 primary retinoblastomas. Interphotoreceptor retinol-binding protein (IRBP), cone and rod opsins were selected as the photoreceptor specific proteins due to their different temporal patterns of expression during normal retinal development. Neoplastic Müller cell differentiation, and non-neoplastic reactive astrocytes were identified using cellular retinaldehyde binding-protein (CRAlBP), and glial fibrillary acidic protein (GFAP), respectively. Photoreceptor proteins were present in 16 cases and showed different cellular patterns of expression. IRBP and cone opsin were usually abundant. Although rod opsin was clearly identified in eight tumors, its expression was more restricted than either IRBP or cone opsin. This differential pattern of expression, opposite to the normal pattern of photoreceptor gene expression in the adult retina, corresponded to a marked decrease in mRNA for rod opsin. Cone opsin and IRBP colocalized in fleurettes demonstrating that neoplastic human cone cells are capable of IRBP synthesis. Müller cell differentiation was present in 12 of the 16 cases in which photoreceptor proteins were detected. In contrast, GFAP was only present in reactive, stromal astrocytes associated with blood vessels. Our data suggest that the retinoblastoma has the histogenetic potential of the immature neural retinal epithelium which can give rise to both photoreceptor and Müller cell lineages. The differential expression of cone and rod phenotypes in retinoblastoma is consistent with the "default" mechanism of cone cell differentiation.

Blotting, Northern↗
PubMed1990

Early expression of the gene for interphotoreceptor retinol-binding protein during photoreceptor differentiation suggests a critical role for the interphotoreceptor matrix in retinal development.

Interphotoreceptor retinol-binding protein (IRBP), the major protein component of the subretinal space, is in a strategic position to mediate cellular interactions between the retinal pigmented epithelium (RPE) and the neural retina. While IRBP appears to be involved in vitamin A transport during the visual cycle in the adult, the role of this protein during eye development has not been determined. As a first step to understanding the role of IRBP during retinal development, we have studied the expression of the mRNA for this glycolipoprotein during photoreceptor differentiation in the rat. A rat neural retina cDNA library was prepared from which an IRBP clone was isolated. The clone contains an open reading frame followed by a 3' noncoding sequence ending in 10 adenosine residues. The coding region has an identity of 83.9 and 82.5% with the nucleotide sequence of human and bovine IRBP, respectively. Rats (Sprague-Dawley, Wistar, and Royal College of Surgeon pink-eyed controls) have a 6.4 and a 5.2-kb mRNA for IRBP which are present in a 1:4 ratio and thus are the only vertebrate known to definitely have more than one major form of the IRBP message. Genomic Southern blots are consistent with the hypothesis that there is only one allele of the IRBP gene, suggesting that the two forms are produced by alternative processing of the mRNA. To generate an antisense RNA probe for use in molecular titration assays and Northern blots, an Eco RI-Bam HI fragment from the coding region was subcloned in between flanking Sp6 and T7 promoters. Total RNA was prepared from undissected rat globes from postnatal days p0-p22. The expression of the mRNA for IRBP was studied by Northern blots and the level of the transcripts determined by solution hybridization assays. Approximately 10(5) IRBP mRNA transcripts/micrograms total eye RNA are present at birth. This increases to a final level of 3.1 X 10(6) transcripts/micrograms total RNA by p9. The one-half maximal level of the mRNA occurs at p4.2 which is 2 wk before the one-half maximal level of IRBP is reached in the subretinal space (Gonzalez-Fernandez, F., R. A. Landers, P. A. Glazebrook, S.-L. Fong, G. I. Liou, D. M. K. Lam, and C. D. B. Bridges. 1984. J. Cell Biol. 99:2092-2098). The expression of the mRNA for IRBP reflects the developmental emergence of the interphotoreceptor matrix as an important structure within the retina.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1989

Sucralfate versus cimetidine in the treatment of reflux esophagitis in children.

Peptic esophagitis is a common complication of gastroesophageal reflux. Therapeutic measures aimed at reinforcing the anti-gastroesophageal reflux barrier, reducing acid secretion, or increasing the defense mechanisms of the esophageal mucosa are used to treat this form of esophagitis. The purpose of this study was to determine the efficacy of sucralfate in the treatment of peptic esophagitis in children. We studied 75 patients diagnosed endoscopically as suffering from esophagitis. The age of the patients ranged from three months to 13 years. Gastroesophageal reflux was diagnosed by isotopic investigation and/or radiologically. None of the patients had kidney disease or had received anti-inflammatory drugs, sucralfate, or cimetidine during the preceding two weeks. The patients were divided into three groups of 25. Patients were homogeneous in age, sex, nutritional status, symptoms, and grade of esophagitis. All patients in each group were treated with cimetidine, sucralfate tablets, or sucralfate suspension. No other dietary or postural measures were prescribed. Clinical examinations were carried out on Days 14, 28, 42, and 56, with an endoscopic examination on Day 28. Endoscopy was repeated on Day 56 if the course was unsatisfactory. Statistical examination of the data showed that there were no differences between the three groups. Sucralfate is a useful drug for the treatment of peptic esophagitis in children.

Adolescent↗
PubMed1985

Interstitial retinol-binding protein (IRBP) in the RCS rat: effect of dark-rearing.

The effect of light- and dark-rearing on the amounts of rhodopsin and interstitial retinol-binding protein (IRBP) in RCS rats and their congenic controls (RCS-rdy+) was determined. Rhodopsin was measured spectroscopically and IRBP by dot-blot enzyme immunoassay utilizing rabbit antibovine IRBP IgG. After P15-20, dark-reared RCS and RCS-rdy+ rats always had more rhodopsin than their light-reared, age-matched counterparts. The rhodopsin in the light-reared RCS rats peaked at about 2 nmol/eye at P20-25. The rhodopsin in the dark-reared RCS rats peaked at about 4 nmol/eye at P60-70. Maintenance of RCS-rdy+ rats in darkness had no effect on their IRBP content, which continued to increase up to P80-110. In both groups of RCS rats, the amount of IRBP reached a peak at P22. In RCS rats maintained in darkness, the amount of IRBP attained at this peak was about twice that in the corresponding light-reared group and in RCS-rdy+ animals at this age. The decline of IRBP after P22 in RCS rats was slowed in darkness by approximately 10 days. This slowed decline of IRBP is associated with a decreased rate of photoreceptor degeneration, and the results are therefore consistent with the hypothesis that the photoreceptors synthesize and secrete IRBP. The layer of membranous debris would restrict the diffusion of IRBP in the subretinal space and could partially exclude this retinol transport protein from access to the zone adjacent to the apical surface of the retinal pigment epithelium (RPE).

Animals↗
PubMed1984

Cardioregulatory nerves in the spider Eurypelma marxi Simon.

The objective of this study was to locate nerves arising from the CNS that have a cardioregulatory function in the tarantula, Eurypelma marxi Simon. Ramifications of the paired abdominal nerve VIIIb merge with the cardiac ganglion within the first heart segment. Electrical stimulation of the branches of nerve VIIIb that connect with the cardiac ganglion produce changes in heartbeat rate and amplitude. Nerve cutting experiments indicate that no other cardioregulatory nerves are present. Both increases and decreases in heart activity can be produced upon electrical stimulation of nerve VIIIb on each side of the heart. Only one action potential associated with the response of each type could be recorded in each member of the nerve pair. Therefore, we conclude that there are two inhibitory and two acceleratory neurons that arise in the central nervous system to modulate heartbeat activity. The inhibitory effect becomes maximal at a stimulation frequency of 20-30 Hz and the accelerator effect at 30-40 Hz. The aftereffect of acceleratory nerve activity exceeds that of inhibitory nerve activity. When the inhibitor and accelerator are activated simultaneously, the inhibitor dominates. The regulatory nerves interact with neurons in the cardiac ganglion. During inhibition, the number of externally recorded spikes in each ganglionic burst is decreased. The rate and magnitude of the heartbeat are decreased concomitantly. Stimulation of the accelerator enhances electrical activity in the cardiac ganglion at the same time that the heartbeat rate and amplitude are increased.

Animals↗
PubMed1984

Visual cycle in the mammalian eye. Retinoid-binding proteins and the distribution of 11-cis retinoids.

This work was designed to provide an insight into the mammalian visual cycle by investigating the possible function of retinoid-binding proteins in this system, and the distribution and type of 11-cis retinoids present in the interphotoreceptor matrix and the cytosols of the retinal pigment epithelium and retina. The total retinol and retinal in the soluble fractions from these three compartments was 8% (3.31 nmol/eye) of the retinyl palmitate and stearate stored in the pigment epithelium membrane fractions (39 nmol/eye). Only small amounts of retinoids were detected in the rod outer segment cytosol. The insoluble fractions also contained retinol, nearly all of which was found in the retina. The retinoids in the soluble fractions appeared to be bound to cellular retinol-binding protein (CRBP), cellular retinal-binding protein (CRA1BP) and interstitial retinol-binding protein (IRBP, a high-Mr glycoprotein). Using immunospecific precipitation, immunoblot and immunocytochemical techniques it was demonstrated that IRBP was localized in the interphotoreceptor matrix and was synthesized and secreted by the retina, a process that did not require the protein to be glycosylated. The amount of retinol bound to IRBP increased if the eyes were exposed to light, when it was estimated that the protein carried up to 30% of its full capacity for all-trans retinol. In addition to all-trans retinol, IRBP carried smaller amounts of 11-cis retinol. The proportion of 11-cis retinol was frequently higher in eyes that had been protected from illumination, suggesting that IRBP plays a role in rhodopsin regeneration during dark-adaptation. Additionally, endogenous 11-cis retinoids in the retina and RPE cytosols were bound to an Mr 33,000 protein tentatively identified as CRA1BP. The 11-cis retinoid in the retina cytosol was mainly in the form of retinol, while in the RPE cytosol it was mainly in the form of retinal. Substantial amounts of 11-cis retinol were also found in the insoluble (membrane) fraction from the retina. It is suggested that in the mammalian retina 11-cis retinol is generated from all-trans retinol (possibly in the Muller cells). Lack of an 11-cis retinol oxidoreductase in the retina prevents it from being utilized for rhodopsin regeneration until it has been transported to the pigment epithelium, where it is converted to 11-cis retinal and returned to the rod outer segments. It is also suggested that IRBP may be implicated in the transport of retinoids between the rod outer segments, the Muller cells and the pigment epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

An extracellular retinol-binding glycoprotein in the eyes of mutant rats with retinal dystrophy: development, localization, and biosynthesis.

Interstitial retinol-binding protein (IRBP) is a soluble glycoprotein in the interphotoreceptor matrix of bovine, human, monkey, and rat eyes. It may transport retinol between the retinal pigment epithelium and the neural retina. In light-reared Royal College of Surgeons (RCS) and RCS retinal dystrophy gene (rdy)+ rats, the amount of IRBP in the interphotoreceptor matrix increased in corresponding proportion to the amount of total rhodopsin through postnatal day 22 (P22). In the RCS-rdy+ rats, the amount increased slightly after P23. However, in the RCS rats there was a rapid fall in the quantity of IRBP as the photoreceptors degenerated between P23 and P29. No IRBP was detected by immunocytochemistry in rats at P28. The amount of rhodopsin fell more slowly. Although retinas from young RCS and RCS-rdy+ rats were able to synthesize and secrete IRBP, this ability was lost in retinas from older RCS rats (P51, P88) but not their congenic controls. The photoreceptor cells have degenerated at these ages in the RCS animals, and may therefore be the retinal cells responsible for IRBP synthesis. The putative function of IRBP in the extracellular transport of retinoids during the visual cycle is consistent with a defect in retinol transport in the RCS rat reported by others.

Aging↗
PubMed1984

Characterization, localization, and biosynthesis of an interstitial retinol-binding glycoprotein in the human eye.

Human eyes contain an Mr 135K retinol-binding protein that is analogous to interstitial retinol-binding protein ( IRBP ) in the subretinal space of bovine eyes. It is a glycoprotein, because it binds 125I-concanavalin A, 125I-wheat germ agglutinin and 125I-Lens culinaris hemagglutinin. It does not bind Ricinus communis agglutinin I. After desialation, it binds Ricinus communis agglutinin I, but loses its capacity to bind wheat germ agglutinin. These observations, coupled with the known specificities of these lectins, suggest that at least one of the oligosaccharide chains is a sialated , biantennary complex type containing fucose. Both by direct analysis of dissected ocular tissues and by immunocytochemistry it was shown that human interstitial retinol binding protein is an extracellular protein that is confined predominantly to the subretinal space. Monkey retinas incubated in vitro in medium containing [3H]leucine were shown to synthesize and secrete this protein into the medium, a conclusion that was confirmed by immunoprecipitation with an immunoglobulin fraction prepared from rabbit antibovine IRBP serum. Virtually no other labeled proteins were detectable in the medium. It is concluded that interstitial retinol-binding protein meets many of the requirements for a putative transport protein implicated in the transfer of retinol between the pigment epithelium and retina during the visual cycle, and that the neural retina may play an important role in regulating its amount in the subretinal space.

Amino Acids↗
PubMed1982

Vitamin A transport between retina and pigment epithelium--an interstitial protein carrying endogenous retinol (interstitial retinol-binding protein).

We have demonstrated and partially characterized an interstitial retinol-binding protein (IRBP) confined to bovine interphotoreceptor matrix (IPM). The native protein is a concanavalin A-binding glycoprotein with a mol. wt of 260 k as measured by gel-filtration and size-exclusion high-performance liquid chromatography. On SDS-gels, its mol. wt is 140-145 k. Since the protein is glycosylated, this value is probably too high. Hence, the native protein may be a dimer consisting of two identical subunits. The endogenous ligand has been analyzed by high-performance liquid chromatography--it consists mainly of all-trans retinol. Occasionally, retinal and 11-cis retinol are also associated with it. The amount of retinol bound to IRBP increases when the eyes are illuminated. The total binding capacity was estimated to represent 4-5% of the retinol released from a total rhodopsin bleach. We have established that, like serum retinol-binding protein, IRBP can be also bind retinoic acid, although it has not been established that retinoic acid is an endogenous ligand. The fluorescence emission lambda max for IRBP with its native ligand is at 470 nm and the excitation lambda max for this fluorescence is at 333 nm. Other retinoid carriers in the interphotoreceptor matrix have molecular weights of about 15 and 33 k. These probably correspond to cellular retinol- and retinal-binding proteins, respectively. Since both proteins have been identified in the pigment epithelium and retina cytosols, their presence in the IPM could be a result of cell damage. We conclude that interstitial retinol-binding protein is the best candidate for a transport protein carrying retinol between the rod outer segments and the pigment epithelium.

Animals↗