Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A glycosphingolipid that reacted positively to anti-stage-specific embryonic antigen-1 (SSEA-1) antiserum accumulated in human lens in association with aging and senile cataract formation. Since this antiserum recognizes Lewis(x) (Le(x)) structure, Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, which is a typical tumor-associated and differentiation-related saccharide chain, the lens glycolipid was predicted to be a Lex antigen. The glycolipid purified from cataractous lens tissues was indeed a Lex glycolipid, Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1- 4Glc beta 1-1 ceramide. Enhanced expression of the Lex glycolipid may affect the organization of lens plasma membranes through Le(x)-Le(x) interactions, as suggested for compaction in mouse preimplantation embryos and embryonic teratocarcinomas, resulting in lens opacification, namely cataract.
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PMID:Senile cataract-related accumulation of Lewis(x) glycolipid in human lens. 134 55

This article reviews standard treatment modalities for patients with glaucoma and describes 3 classes of drugs which are undergoing development: apraclonidine (aplonidine, ALO 2145), an alpha 2-adrenergic agonist which has been released for clinical use; topical carbonic anhydrase inhibitors, a modification of the systemic carbonic anhydrase inhibitors currently in use; and prostaglandins (PGs), a new class of drugs with topical ocular hypotensive activity. Standard treatment modalities include parasympathomimetic agents such as pilocarpine, carbachol, and phospholine iodide, which lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork. A newer form of pilocarpine as a gel produces a longer action. Adrenergic agonist medications, such as epinephrine (adrenaline) and its prodrug dipivefrine (dipivalyl epinephrine), function by increasing uveoscleral outflow and trabecular outflow facility. A decrease in aqueous formation by the ciliary processes is thought to be the mechanism of action of beta-adrenoceptor antagonists, but the physiological basis for this action has not been clearly demonstrated. A newer beta-blocker, betaxolol, has relatively selective beta 1-blocking activity. Carbonic anhydrase inhibitors are nonbacteriostatic sulphonamide derivatives which decrease aqueous formation by the ciliary body. Almost 50% of patients taking these medications are unable to tolerate them because of their adverse effects, and there is thus much interest in the development of a topical carbonic anhydrase inhibitor with the potential for fewer adverse effects. MK 507 is the most recent and most potent compound in the series of topically active carbonic anhydrase inhibitors. Apraclonidine hydrochloride is a derivative of clonidine hydrochloride, an alpha 2-adrenergic agonist. Clonidine has previously been shown to lower IOP significantly, but has the potential to produce marked lowering of both systolic and diastolic blood pressures. Its major ocular effect appears to be a decrease in aqueous production. The structural modification to apraclonidine decreases corneal absorption and the drug's ability to cross the blood-brain barrier, minimising the risk of centrally mediated cardiovascular side effects. Apraclonidine may also influence secondary avenues of aqueous outflow, such as uveoscleral outflow, and may also affect conjunctival and episcleral vascular flow. It produces a mean decrease in IOP of 25% for as long as 12 hours. Adverse effects include blanching of the conjunctiva, minimal mydriasis and eyelid retraction. This drug has been approved in the US for use in prevention of elevated IOP after argon laser trabeculoplasty and iridotomy, and has potential uses in preventing an IOP rise after YAG laser posterior capsulotomy and cataract surgery in patients already on other antiglaucomatous medications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in the drug treatment of glaucoma. 171 57

The transforming growth factor-beta s are peptide growth factors known to play a central role in wound healing. Using a specific, in vitro assay of cell growth inhibition, we have detected transforming growth factor-beta (TGF-beta) in 24/24 aqueous humor specimens from eyes undergoing cataract extraction with intraocular lens implantation. The amount of TGF-beta ranged from 2.3 to 8.1 ng/ml (mean +/- SD = 4.5 +/- 1.7 ng/ml), with 61% present in the active form. Subtyping of TGF-beta was performed by addition of antibodies specific for the beta 1 and beta 2 isoforms to the growth inhibition assay, and confirmed with a sandwich enzyme-linked immunosorbent assay. None of the TGF-beta detected was of the beta 1 isoform; in contrast, the beta 2 isoform was present in every sample, implying that it might have originated from ocular tissues. The presence of this potent modulator of tissue repair in aqueous humor suggests a role in the healing processes following intraocular surgery, including glaucoma filtration surgery.
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PMID:Transforming growth factor-beta in human aqueous humor. 227 73

beta-Crystallins (beta 1-, beta 2- and beta 3-crystallin) comprise nearly half the protein of the human lens. The effect of near-UV radiation, which is one of the possible risk factors in cataract formation, on the beta-crystallins is investigated in this study. Protein intersubunit crosslinking, change in charge of the protein subunits to more acidic species and changes in protein tertiary structure (conformation) by 300 nm irradiation are reported. The fluorescence yield of protein tryptophan residues decreases by 300 nm irradiation. There is an increase in nontryptophan fluorescence (lambda cx 340 nm, lambda cm 400-600 nm), and in protein absorption at 340 nm, due to the formation of tryptophan photooxidation products. Both tryptophan and its oxidation products can be photoexcited by 300 nm irradiation and the latter are known to be good photosensitizers. The results provide evidence for the generation of H2O2 in the irradiated human beta-crystallin solutions by the Type I photosensitizing action of the chromophores absorbing at 300 nm. The H2O2 is generated via the intermediate production of O2 anion; the latter spontaneously dismutates to H2O2, presumably via O2- protein interactions. The amount of H2O2 generated per absorbed photon is compared for various solutions of beta 1-, beta 2- and beta 3-crystallins from human lenses of different age.
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PMID:The effects of near-UV radiation on human lens beta-crystallins: protein structural changes and the production of O2- and H2O2. 276 85

Extracts of water-soluble proteins from cortex and nucleus of single human lenses have been analyzed by high-pressure gel permeation chromatography in combination with a size- and a concentration-sensitive detector. Using this rapid and accurate method, changes in molecular weight and proportion of the native crystallins upon aging and formation of nuclear cataract are observed. In the range from 30 to about 40 years the gamma-crystallin content of normal lenses increases and that of alpha-crystallin decreases; over 40 years the level of gamma-crystallin decreases and that of alpha-crystallin remains constant in the cortex (11%) as well as in the nucleus (1-2%). These changes are accompanied by an increase in the water-insoluble fraction. With progressing nuclear cataract an increase in beta 3- and a drastic decrease in gamma-crystallin content, especially in the nucleus, are accompanied by a steep increase in the water-insoluble fraction. The molecular weights of the crystallins do not change significantly, except that of alpha- and beta 1-crystallin which show an increase with age.
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PMID:Variation in proportion and molecular weight of native crystallins from single human lenses upon aging and formation of nuclear cataract. 666 9

Spindle-shaped myofibroblast-like cells, which contain alpha-smooth muscle actin, have been described in anterior subcapsular cataract and after-cataract. In a previous study in this laboratory, it was shown that transforming growth factor-beta (TGF beta) induces the formation of spindle-shaped cells in lens epithelial explants. The aim of this investigation was to determine whether these TGF beta-induced spindle-shaped cells contain alpha-smooth muscle actin. Lens epithelial explants were prepared from 21-day-old rats and cultured with either TGF beta 1 or basic FGF alone, a combination of both growth factors, or without added growth factors. After three days, cellular changes were monitored by phase contrast microscopy, localisation of filamentous actin with rhodamine-phalloidin, and immunolocalisation and immunoblotting of alpha-smooth muscle actin. TGF beta induced rapid cell elongation and formation of characteristic spindle-shaped cells in lens epithelial explants in the presence or absence of FGF. These cells contained alpha-smooth muscle actin, a marker for myofibroblastic cells and a protein not normally found in the lens. The present study thus provides molecular evidence that TGF beta induces cataractous changes in lens epithelial cells. As TGF beta is potentially available to lens cells in situ throughout life, these findings are consistent with a key role for TGF beta in the aetiology of major forms of subcapsular cataract.
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PMID:TGF-beta 1 induces lens cells to accumulate alpha-smooth muscle actin, a marker for subcapsular cataracts. 772 Mar 96

Human lens accumulates gangliosides in association with aging and senile cataract progression. In this study we purified and characterized five major gangliosides in human cataractous lenses. Structural analyses and immunological studies revealed the presence of ganglio-series gangliosides, GM3, GM2, GM1 and GD1a, and a sialyl-Lewisx-containing neolacto-series ganglioside, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1ceramide (IV3NeuAcIII3FucnLc4). Slow-moving gangliosides, although minor components, were also found to have sialyl-Lewisx-related structures, based on anti-Lewisx antiserum binding to their asialo forms. However, sialyl-paragloboside, a possible precursor of the sialyl-Lewisx ganglioside, was not identified.
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PMID:Identification and synthetic pathway of sialyl-Lewisx-containing neolacto-series gangliosides in lens tissues. 1. Characterization of gangliosides in human senile cataractous lens. 776 94

Gel filtration of water-soluble protein shows a substantial increase in HM+ alpha-crystallin and a marked decrease in beta- and gamma-crystallins in cortical cataract. A decrease in beta 1-crystallin in cortical punctate opaque lenses is also striking. In nuclear cataractous lenses HM+ alpha- and beta-crystallin increase, while gamma-crystallin decreases. The urea-soluble protein from clear lenses contains mainly of alpha beta chain, whereas in cataractous lenses the relative amounts of the 28 and 23ku polypeptides (the components of beta-crystallin) increased markedly. In cataractous lenses the relative amount of membrane intrinsic proteins decreases slightly and it has little statistical meaning.
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PMID:[Changes in water-soluble, urea-soluble and membrane intrinsic proteins in human senile cataract]. 784 96

We have studied the glycolipid composition of human cataractous lenses. Neutral and acidic lipid fractions were isolated by column chromatographies on DEAE-Sephadex and Iatrobeads. The neutral glycolipid fraction and acidic glycolipid fraction contained 0.6-0.9 micrograms of lipid-bound glucose (Glc) per mg of protein and 0.8-1.3 micrograms of lipid-bound sialic acid (NeuAc) per mg of protein, respectively. The neutral glycolipid fraction was found to contain LacCer (39.0% of total neutral glycolipids), Gb3 (16.2%), Gb4 (1.1%), nLc4 (5.0%), X (29.0%), and Y (9.2%). The acidic lipid fraction was found to contain mainly GM3 (33.1% of the total ganglioside fraction), GM1 (8.3%), LM1 (7.3%), GD1a (16.0%), and G (30.1%). The structures of neutral glycolipids X and Y and ganglioside G were elucidated by high performance thin-layer chromatography overlay method of glycolipids, gas-liquid chromatography, proton NMR spectrometry, and liquid secondary ion mass spectrometry as follows: 1) X, Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer, III3FucnLc4 (Lex); 2) Y, Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1- 3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer, V3FucIII3FucnLc6; and 3) G, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3 Gal-beta 1-4Glc beta 1-1'Cer, IV3NeuAcIII3FucnLc4 (sialosyl-Le(x)). A minor neutral glycolipid Z was isolated and tentatively characterized as GlcNAc beta 1-3?Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer (GlcNAc-Le(x)), suggesting that it may be the precursor of glycolipid Y. The major long-chain base of these human cataract glycolipids was C18:0 sphingosine (sphinganine). The major fatty acids were C16:0, C24:1 and C24:0, and monounsaturated fatty acids accounted for 40-55% of the total fatty acids.
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PMID:Glycolipid composition of human cataractous lenses. Characterization of Lewisx glycolipids. 790 80

Aqueous humour concentrations and antagonist activity of betaxolol were studied after ocular administration in forty-five patients scheduled for cataract surgery. The patients were randomly divided into five groups and received 40 microliters of 0.5% betaxolol into the lower cul-de-sac of one eye. In groups I, II, III and IV the drug was instilled 5-6, 12, 24 and 48 h, respectively, before surgery, into the eye to be operated, and in group V 4 h before surgery into the contralateral eye. Aqueous humour samples were aspirated at the beginning of the operation. Aqueous humour concentrations of betaxolol were analyzed using a radioreceptor assay, and the ex-vivo-beta 1- and beta 2-receptor occupancies of betaxolol were calculated. The highest concentration of betaxolol in aqueous humour was found 5-6 hours after instillation of the drug. Topical betaxolol was found to stay in aqueous humour for 48 h, a much longer time than the recommended interval of dosage. Betaxolol beta 1-receptor occupancy was 99-95% during the study, but also beta 2-receptor occupancy was significant (52%) 24 h after instillation of the drug. Because receptor occupancy is the basis of antagonist activity, the role of beta 2-receptor blocking effect of betaxolol in lowering intraocular pressure cannot be excluded.
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PMID:Concentrations and antagonist activity of topically applied betaxolol in aqueous humour. 790 73


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