Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen patients with keratinising dermatoses were treated for 2-17 weeks with oral 13-cis retinoic acid. There was near complete clearing of the skin lesions beginning within 2 weeks of starting treatment in all five patients with lamellar ichthyosis (including two cases of non-bullous congenital ichthyosiform erythroderma), in two of the three patients with Darier's disease, and in one patient with pityriasis rubra pilaris. The patients with psoriasis and naevus comedonicus did not improve. The main form of toxicity was cheilitis. These results indicate that 13-cis retinoic acid may be more effective and is less toxic than naturally occurring retinoic acid (all-trans vitamin A acid), and that the synthetic retinoids may represent a potent new class of drugs in the treatment of cutaneous disease.
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PMID:Treatment of lamellar ichthyosis and other keratinising dermatoses with an oral synthetic retinoid. 6 99

The partition of cis-parinaric acid (9,11,13,15-cis, trans, trans,cis-octadecatetraenoic acid, cis-PnA) and trans-parinaric acid (9,11,13,15-all-trans-octadecatetraenoic acid, trans-PnA) among aqueous, solid lipid, and fluid lipid phases has been measured by three spectroscopic parameters: absorption spectral shifts, fluorescence quantum yield, and fluorescence polarization. The solid lipid was dipalmitoylphosphatidylcholine (DPPC); the fluid lipid was palmitoyldocosahexaenoylphosphatidylcholine (PDPC). Mole fraction partition coefficients between lipid and water were determined by absorption spectroscopy to be for ci--PnA, 5.3 X 10(5) with a solid lipid and 9 X 10(5) with fluid lipid and, for trans-PnA, 5 X 10(6) with solid lipid and 1.7 X 10(6) with fluid lipid. Ratios of the solid to the fluid partition coefficients (Kps/f) are 0.6 +/- 0.2 for cis-PnA and 3 +/- 1 for trans-PnA. A phase diagram for codispersions of DPPC and PDPC has been constructed from the measurements of the temperature dependence of the fluorescence quantum yield and polarization of cis-PnA and trans-PnA and their methyl ester derivatives. A simple analysis based on the phase diagram and fluorescence data allows additional calculations of Kps/f's which are determined to be 0.7 +/- 0.2 for the cis probes and 4 +/- 1 for the trans probes. The relative preference of trans-PnA for solid phase lipids and its enhanced quantum yield in solid phase lipids make it sensitive to a few percent solid. The trans probes provide evidence that structural order may persist in dispersions of these phospholipids 10 degrees C or more above their transition temperature. It is concluded that measurements of PnA fluorescence polarization vs. temperature are better suited than measurements of quantum yield vs. temperature for determining phospholipid phase separation.
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PMID:Phospholipid lateral phase separation and the partition of cis-parinaric acid and trans-parinaric acid among aqueous, solid lipid, and fluid lipid phases. 43 80

Biochemical and immunological techniques were used to determine the emergence of interstitial retinol binding protein (IRBP), rhodopsin, and stored retinyl esters (all-trans and 11-cis) during retinal development in normal and rd mice. IRBP could be demonstrated at embryonic Day 17 (E17), corresponding to an early stage of inner segment development. Although all-trans retinyl esters were present earlier, 11-cis retinyl esters did not appear until postnatal Days 6-7 (P6-P7), corresponding to rod outer segment (ROS) disc formation. Rhodopsin was detected at the same developmental stage. The proportion of 11-cis retinyl esters reached a maximum of 40-50% at P15-P20. Thereafter, the proportion dropped, due to more rapid accumulation of the all-trans isomer. Rhodopsin and IRBP increased in parallel with ROS elongation up to P25, when the ROS had reached their mature lengths. The increases then continued up to P40-P50. In rd (retinal degeneration) mice, IRBP and rhodopsin were identical with the controls until P12, but then dropped as the photoreceptors degenerated. Synthesis and secretion of IRBP in vitro was less than 10% of the controls in rd retinas at P26, when only 4-5% of the photoreceptors survived. The quantities of retinyl esters (mainly stearate and palmitate in the ratio of 6:1, respectively) stored in dark-adapted mouse eyes progressively increased as the animals aged, representing 0.5 mole eq. of the rhodopsin at 8 months. Although retinyl esters (11-cis and all-trans) also accumulated in rd mouse eyes up to P12, little further increase occurred. At P93, the retinyl esters (0.01 nmole X eye-1) were only 4% of the controls at P91. A peak in the proportion of 11-cis isomer occurred at P10-P20, but it averaged only 15% of the total ester and declined to 5% at P93. These findings support the hypothesis that IRBP is synthesized by the rods and cones, and suggest that its synthesis and secretion are initiated when the photoreceptor inner segments start to differentiate. 11-cis Retinoids and rhodopsin do not appear until the outer segments start to form. It is suggested that in the rd mouse the absence of photoreceptors, perhaps coupled with lack of normal interphotoreceptor matrix, leads to a loss in the ability of the pigment epithelium to store retinyl esters.
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PMID:Rhodopsin, 11-cis vitamin A, and interstitial retinol-binding protein (IRBP) during retinal development in normal and rd mutant mice. 373 15

The interactions in mixed monolayers between distearoyl-L-phosphatidylethanolamine, natural phosphatidylethanolamine purified from bovine rod outer segments and all-trans retinal have been studied at the nitrogen/water interface at 21.0 +/- 0.5 degrees C. Seven mixtures of each phospholipid with all-trans retinal, covering the whole range of molar fractions, were studied. The monolayers were spread on a 1 X 10(-3) M phosphate buffer subphase at three different pH values, 5.5, 7.1 and 8.2. The results for the two series of mixtures are strikingly different. The surface phase rule shows that all-trans retinal is miscible with the natural phospholipid at the interface. Small, negative deviations with respect to the additivity rule are observed in this case. The excess free energies of mixing were also calculated as a function of concentration for this system at four different surface pressures, 5, 7, 10 and 13 mN X m-1. They are negative for the four surface pressures considered and symmetrical with respect to the mole fraction. On the other hand, when distearoyl-L-phosphatidylethanolamine is mixed with all-trans retinal, the components are no longer miscible at the interface. This marked difference in behaviour between the two lipids reflects the importance of hydrophobic interactions in the mixed monolayers of phospholipids with retinals. Furthermore, for the two series of mixtures, the surface pressure isotherms do not show any significant shift when the subphase pH is changed from 5.5 to 8.2. This behaviour raises questions about the formation of a Schiff base between phosphatidylethanolamine and retinal at the interface. It is suggested that, owing to the nature of the disk membranes, such an effect would also be observed in vivo. The possible implications of this are discussed, particularly with respect to questions pertaining to the stability of the retinal chromophore.
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PMID:Interactions in mixed monolayers between distearoyl-L-phosphatidylethanolamine, rod outer segment phosphatidylethanolamine and all-trans retinal. Effect of pH. 684 5

The amount, distribution, and composition of vitamin A stored in the eyes of 29 postmortem donors was determined by a combination of techniques, including high-pressure liquid chromatography. The vitamin A concentration in the pigment epithelium-choroid (RPE-Ch) was the highest observed for human non-liver tissue and amounted to 7.9 +/- 4.3 nmol/eye (n = 28), or 10.4 +/- 7.1 microgram/gm (n = 27). There was no evidence for significant losses during the interval between death and enucleation or during subsequent storage at 4 degrees C. The vitamin A extracted from the retina was 15.3% of that in the corresponding RPE-Ch. By measuring rhodopsin regeneration in retinal homogenates incubated with 11-cis retinal, we estimated that the amount of vitamin A in the RPE-Ch of fully dark-adapted eyes would represent 2.5 mole equivalents of the retinal rhodopsin, a value similar to that found in the frog. A preponderance of the vitamin A in the eye was esterified (98.3% in the RPE-Ch, 79.3% in the retina) and consisted principally of stearate and palmitate in the ratio of 1:4.8. A small amount of oleate was also detected. The ratio of 11-cis isomer over the all-trans averaged 1.52 +/- 0.48 (n - 11). Variable, usually small proportions of 13-cis retinyl esters were also present. Intact RPE-Ch or isolated RPE cells esterified exogenous all-trans-3H2-retinol to the same fatty acids in roughly the same proportions as in the endogenous stores. The all-trans configuration was mainly retained during uptake and esterification, although some isomerization to 13-cis also occurred. No 11-cis isomer was formed under these conditions.
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PMID:Vitamin A in human eyes: amount, distribution, and composition. 707 16

In order to develop an intravenous formulation of all-trans-retinal (vitamin A aldehyde, VAA) for the treatment of night blindness, VAA and dipalmitoylphosphatidylcholine (DPPC) were sonicated and the dispersions in the VAA mole fraction range of 0.1-0.7 were stable at room temperature for 3 days. In order to clarify the dispersal mechanism, the dispersed particles were characterized and the interaction between VAA and DPPC was investigated using several physicochemical techniques. Dynamic light scattering measurements showed that the diameter of the dispersed particles was 50-70 nm. A limited amount of VAA is incorporated into DPPC bilayer membranes (approximately 5 mole%). The trapped aqueous volume inside the particles was determined fluorometrically using the aqueous space marker calcein and the volume in the VAA/DPPC particles was decreased remarkably with the addition of VAA into small unilamellar vesicles of DPPC. The decline in the fraction of vesicular particles was also confirmed by fluorescence quenching of N-dansylhexadecylamine in the DPPC membrane by the addition of the quencher CuSO(4). These results indicate that the excess VAA separated from the DPPC bilayers is stabilized as emulsion particles by the DPPC surface monolayer. The monolayer-bilayer equilibrium of VAA/DPPC mixtures was estimated by measurement of spreading and collapse pressures. The results showed that the coexistence of emulsion particles (surface monolayer of DPPC+core of VAA) with vesicular particles (bilayer) was critically important for the formation of the stably dispersed particles of the lipid mixture.
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PMID:Formation and structure of stably dispersed particles composed of retinal with dipalmitoylphosphatidylcholine: coexistence of emulsion particles with bilayer vesicles. 1047 32

Although a variety of topical treatments have been used for skin hyperpigmentation, the effectiveness of each varies after prolonged treatment. In this study, 136 Oriental patients who were followed up for more than 12 weeks were analyzed. The treatment protocol was composed of two steps: bleaching (2 to 6 weeks) and healing (2 to 6 weeks); 0.1% to 0.4% all-trans retinoic acid aqueous gel was originally prepared and applied concomitantly with hydroquinone-lactic acid ointment for bleaching. After obtaining sufficient improvement of the hyperpigmentation, a corticosteroid was applied topically with hydroquinone and ascorbic acid for healing. Improvement was evaluated with a narrow-band reflectance spectrophotometer. The results were successful in more than 80 percent of cases of senile lentigines and postinflammatory hyperpigmentations, especially on the face. Sixty percent of cases of nevus spilus were also successfully treated. Although the transient adverse effects of this treatment may be more severe than conventional treatment, this strong bleaching protocol improves a variety of hyperpigmented lesions, including nevus spilus, with a higher success rate and a shorter treatment period than conventional protocols.
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PMID:Experience with a strong bleaching treatment for skin hyperpigmentation in Orientals. 1072 72

As a depigmenting treatment, combined topical applications of all-trans retinoic acid (atRA) aqueous gel and 5% hydroquinone, 7% lactic acid ointment were used for Oriental patients with hyperpigmented skin lesions such as senile lentigines and nevus spilus. A narrow-band reflectance spectrophotometer and a tristimulus colorimeter were used to evaluate objectively the intensity of pigmentation and erythema at each clinical visit. L*, a*, and b* values measured with a tristimulus colorimeter (Chroma Meter CR-300) enabled the evaluation of erythema but not pigmentation. On the other hand, the melanin and hemoglobin values measured with a narrow-band reflectance spectrophotometer (Mexameter MX-16) expressed both erythema and pigmentation well. It was revealed that, in our bleaching protocol, the narrow-band reflectance spectrophotometer was quite useful for estimating accurately the intensity of pigmentation and erythema and determining the best time point for the cessation of atRA treatment.
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PMID:Usefulness of a narrow-band reflectance spectrophotometer in evaluating effects of depigmenting treatment. 1134 3

The molar extinction of rhodopsin is 40,600 cm.(2) per mole equivalent of retinene; i.e., this is the extinction of a solution of rhodopsin which is produced by, or yields on bleaching, a molar solution of retinene. The molar extinctions of all-trans retinene and all-trans retinene oxime have also been determined in ethyl alcohol and aqueous digitonin solutions. On the assumption that each chromophoric group of rhodopsin is made from a single molecule of retinene, it is concluded that the primary photochemical conversion of rhodopsin to lumi-rhodopsin has a quantum efficiency of 1; though the over-all bleaching of rhodopsin in solution to retinene and opsin may have a quantum efficiency as low as one-half. On bleaching cattle rhodopsin, about two sulfhydryl groups appear for each molecule of retinene liberated. In frog rhodopsin the -SH:retinene ratio appears to be higher, 5:2 or perhaps even 3:1. Some of this sulfhydryl appears to have been engaged in binding retinene to opsin; some may have been exposed as the result of changes in opsin which accompany bleaching, comparable with protein denaturation.
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PMID:The molar extinction of rhodopsin. 1310 55

ABCA4, a member of the family of ATP binding cassette (ABC) proteins found in rod and cone photoreceptors, has been implicated in the transport of retinoid compounds across the outer segment disk membrane following the photoactivation of rhodopsin. Mutations in the ABCA4 gene are responsible for Stargardt macular dystrophy and related retinal degenerative diseases that cause a loss in vision. To identify the retinoid substrate that interacts with ABCA4, we have isolated ABCA4 from rod outer segment disk membranes on an immunoaffinity matrix and analyzed retinoid compounds that bind to ABCA4 using high performance liquid chromatography and radiolabeling methods. When all-trans-retinal was added to ABCA4 in the presence of phosphatidylethanolamine, approximately 0.9 mol of N-retinylidene-phosphatidylethanolamine and 0.3 mol of all-trans-retinal were bound per mol of ABCA4 with an apparent K(d) of 2-5 microm. ATP and GTP released these retinoids from ABCA4, whereas ADP, GDP, and nonhydrolyzable derivatives, adenosine 5'-(beta,gamma-imido)triphosphate and guanosine 5'-(beta,gamma-imido)triphosphate, were ineffective. One mole of N-retinyl-phosphatidylethanolamine, the reduced form of N-retinylidene-phosphatidylethanolamine, bound per mol of ABCA4, whereas 0.3 mol of all-trans-retinal were bound in the absence of phosphatidylethanolamine. No binding of all-trans-retinol to ABCA4 was observed. Our results indicate that ABCA4 preferentially binds N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP. Our studies further suggest that ATP binding and hydrolysis induces a protein conformational change that causes N-retinylidene-phosphatidylethanolamine to dissociate from ABCA4.
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PMID:N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR). 1547 66


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