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Biomedical subjects

E Cotlier

Publications and source records attributed to E Cotlier.

At least 37 records · Page 2Linked to original sources

Urea cycle enzymes in retina, ciliary body-iris, lens and senile cataracts.

Carbamylation of lens proteins induced conformational changes and may play a role in the development of cataracts in uremic patients. Thus, the activities of the urea cycle enzymes: carbamyl phosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinase and arginase, were determined in lens, retina and ciliary body-iris of calf and rabbit. No ornithine transcarbamylase activity was found in ciliary body-iris, lens and retina of calf and rabbit whereas carbamyl phosphate synthetase I, argininosuccinate synthetase, argininosuccinase and arginase activities in calf lens were 5.02 +/- 0.21, 9.50 +/- 0.29, 9.17 +/- 0.16 and 6.32 +/- 0.19 [mumol (g protein)-1 hr-1], respectively. Except arginase, the activities of carbamyl phosphate synthetase I, argininosuccinate synthetase and argininosuccinase in lens were 30-50% of the values in retina or ciliary body-iris. The Km for each of the substrates was obtained for argininosuccinate synthetase, argininosuccinase and arginase of calf lens. Activities of carbamyl phosphate synthetase I, argininosuccinate synthetase, argininosuccinase and arginase in clear human lenses, aged 67-87 years, were 0.11 +/- 0.01, 0.67 +/- 0.01, 0.20 +/- 0.01 and 0.58 +/- 0.03 (mumol lens-1 hr-1), respectively. Two-fold increase in the activity of arginase was found in senile cataracts, but all other enzymes had 36-87% decreases in activities. It is likely that the rise in arginase activity in cataracts could facilitate polyamine synthesis through ornithine and ornithine decarboxylase and additional formation of cyanate, a carbamylating compound, both of which have been implicated in cataract formation. Further, decreased activities of argininosuccinate synthetase and argininosuccinase together with increased arginase activity could lead to the depletion of arginine in senile cataracts.

Aged↗

A new family of fucose-containing gangliosides isolated from human senile cataracts.

Gangliosides were isolated from human cataracts by solvent extraction, silicic acid chromatography, thin-layer chromatography and gas-liquid chromatography. A total of 11 resorcinol-positive bands were revealed by thin-layer chromatography. Bands 1, 5 and 7 were partially identified as hematoside. GM1 ganglioside and disialoganglioside by gas-liquid chromatography as the O-trimethylsilylated methylglycosides. In addition to galactose and glucose, fucose was found to be present in seven ganglioside fractions (bands 3, 4, 6 and 8-11). All these fucolipids contained N-acetylglucosamine in addition to sialic acid. Fucogangliosides G-3, G-4 and G-6 contained a 2:1 molar ratio of galactose to glucose, while G-8 had a galactose/glucose molar ratio of 1:1. Long-chain fatty acids constituted 60-77% of the total normal fatty acids in N-acetylgalactosamine-containing gangliosides, whereas the fucogangliosides contained primarily palmitate, although significant amounts of long-chain acids were also detected. The major long-chain base of the fucoganglioside was sphinganine (dihydrosphinogosine). The role of fucose-containing gangliosides in maintaining adhesions between lens membranes in cataracts is discussed with reference to glycosphingolipids in other tissues.

Cataract↗

Distribution of salicylate in lens and intraocular fluids and its effect on cataract formation.

Retrospective studies on cataract development in patients with rheumatoid arthritis or osteoarthritis revealed a retardant effect of aspirin on diabetic and non-diabetic cataracts. The effect of aspirin is dose-dependent. The correlation coefficient between years delay for various cataracts subcategories versus aspirin taken (in tablets per day X years of intake) was 0.69. The ocular pharmacokinetics of 14C acetylsalicylic acid or salicylate were determined after intravenous or intraperitoneal administration to rabbits. 14C acetylsalicylic acid penetrates rapidly into rabbit lens and aqueous humor after intravenous administration. After intraperitoneal administration, salicylate levels in rabbit plasma, similar to those of humans receiving four to six aspirin tablets (325 mg each), result in accumulation of salicylate by lens (mean +/- SD) of 405 +/- 72 mumoles/g and 620 +/- 30 mumoles/g at two and four hours, respectively. At those dosages, salicylate is cleared in 24 hours from rabbit plasma and intraocular fluids, but retained by lens. Penetration of salicylate into rabbit lens and rat lens is dose-dependent. The retardant aspirin effect in diabetic cataracts is linked to inhibition of tissue aldose reductase and lens protein glycosylation. Deceleration of galactose cataract formation in rats occurs after daily salicylate intraperitoneal injections of 100 mg/kg a day.

Animals↗

Fate of insulin in the retina: an autoradiographic study.

A system for whole-blood perfusion of the bovine eye through the cilioretinal artery was developed and the distribution and binding of 125I-labelled insulin and human growth hormone (HGH) were studied autoradiographically. Sodium fluorescein was used as a tracer to monitor blood retinal barrier integrity, and electron microscopy was used to determine structural preservation after perfusion fixation. With this system, barrier integrity and structural perservation of both the neural retina and the retinal blood vessels were regularly obtained, with perfusion periods of as long as 5 hours. By quantitative light microscopy autoradiography, insulin binding sites were identified on the endothelial cells of retinal capillaries after perfusion with blood containing 125I-insulin. 125I-insulin binding was competitively inhibited by the addition of unlabelled insulin to the perfusing blood. By contrast the low level of binding of HGH to retinal capillaries was nonspecific. Electron microscopy autoradiography revealed 125I-insulin autoradiographic grains lying over the endothelial cell wall, over pinocytotic vesicles, and over the cytoplasm of both endothelial cells and pericytes. This suggests that, after binding to the cell surface, some insulin passes into the cell cytoplasm. However, neither 125I-HGH penetrated as far as the retina in the periods studied.

Animals↗

Insulin receptors in calf and human retinal blood vessels.

A system for isolation of capillaries from the retina has been adapted to biochemical studies in vitro. Insulin receptors were identified in human and calf retinal blood vessels. Binding of 125I insulin by calf retinal blood vessels takes place through high affinity (low capacity) and low affinity (high capacity) receptor sites. Insulin binding is inhibited by glucagon, and cGMP and proinsulin. Dissociation of insulin receptor protein or lipid with Triton X-100 or phospholipase results in significant decreases in 125I insulin binding by retinal blood vessels. Dissociation of insulin bound occurs only at 0 degrees C which may be due to rapid internalization of insulin at higher temperatures. Activities of cAMP and cGMP phosphodiesterases and cyclase of retinal vessels were not significantly changed by incubation with insulin. At high concentrations in the media human growth hormone stimulates and then inhibits I125 insulin binding by retinal capillaries.

Aged↗

Studies on glutathione S-transferase, glutathione peroxidase and glutathione reductase in human normal and cataractous lenses.

The cause(s) for decreased reduced glutathione (GSH) content of human senile cataracts were investigated by determination of three enzymes of GSH metabolism: GSH S-transferase, GSH peroxidase and GSH reductase. There are significant decreases in activities of GSH S-transferase of early cataracts (-76%) and of dark advanced cataracts (-73%) as compared to clear age-matched lenses. However, the activities of GSH peroxidase were only slightly decreased in cataracts as compared to clear age-matched lenses. The decrease in enzymes of GSH metabolism does not account for increased GSH degradation. Thus decreased GSH synthesis and leak out from cataractous lenses may account for the GSH loss in cataracts.

Adult↗

Diabetic complications in lens and nerve and their prevention by sulindac or sorbinil: two novel aldose reductase inhibitors.

Sorbitol, resulting from glucose metabolism through aldose reductase, may play a role in diabetic complications such as cataracts, neuropathy, and vasculopathy. Sulindac (Clinoril) and sorbinil, two inhibitors of aldose reductase, decreased sorbitol formation in cataract or nerve tissue incubated in high glucose TC-199 media. Sulindac, a widely used anti-rheumatic drug, may have clinical applications in preventing diabetic complications.

Aldehyde Reductase↗

Methods for evaluation of medical therapy of senile and diabetic cataracts.

Loss of transparency in the human lens can be documented by a variety of methods including: (a) slit lamp photography with or without corrections for depth of focus; (b) retroillumination photography alone or coupled to densitometry; (c) high resolution targets projected into the eye and visualized by an ophthalmoscope; (d) drawings and/or measurements of lens opacities; (e) visual acuity determinations after visualization of the macular area and complete eye examination. The advantages and practical uses of each method were reviewed with reference to its value in determining the progression of cataracts in humans. Diabetes accelerates cataract development as determined from graphic plots of cataracts classified after surgical extraction vs the patient's age. Using similar methods high aspirin dosages administered through many years were found to decelerate cataract progression. Drugs for preventing development of diabetic cataracts in animals include inhibitors of aldose reductase or glycosylation such as sulindac (Clinoril), sorbinil or aspirin.

Aged↗

Aspirin effect on cataract formation in patients with rheumatoid arthritis alone or combined with diabetes.

The prevalence of cataracts is significantly lower in patients with rheumatoid arthritis receiving aspirin (mean of 2,700 mgs daily for an average of 10.4 years) as compared to the matched population not receiving aspirin. Similarly, fewer cataracts were found among a population with diabetes and rheumatoid arthritis receiving aspirin (mean of 2,340 mgs daily for an average of 8.8 years) as compared to the matched population on no aspirin. The effects of aspirin on cataract formation may result from 1) lowering of plasma tryptophan levels and increased excretion of tryptophan metabolites, 2) inhibition of aldose reductase and sorbitol formation in the diabetic lens, 3) inhibition of tryptophan or kynurenine binding to lens protein.

Aged↗

Hermansky-Pudlak syndrome: albinism with lipofuscin storage.

The Hermansky-Pudlak Syndrome, a "tyrosinase positive' form of oculocutaneous albinism, is a triad comprising albinism, a hemorrhagic diathesis and ceroid-lipofuscin storage. A pedigree is presented showing consanguinity with a pattern of pseudodominance. Electroretinography in two isolated Hermansky-Pudlak subjects was distinctly abnormal, showing decreased rod and cone responses (as well as abnormal flicker fusion responses) in one patient, and reduced photopic and scotopic responses in another. The decreased ERG responses are discussed with reference to the known retinal abnormalities in both generalized oculocutaneous albinism and Batten's disease, another ceroid-lipofuscin storage disorder.

Adolescent↗

Dinitrochlorobenzene immunotherapy of recurrent squamous papilloma of the conjunctiva.

Dinitrochlorobenzene (DNCB) immunotherapy of a recurrent conjunctival papilloma was employed successfully in a 24-year-old man. Previous attempts at electrocautery, surgical excision, and cryosurgery met without success. The tumor response to DNCB therapy resulted in total eradication of the tumor and represents a more successful modality than previous treatments. Poor patient compliance, variable patient immune mechanisms, and tumor size may influence the variable patient immune mechanisms, and tumor size may influence the fate and type of response to DNCb immunotherapy. DNCB therapy should be considered in the treatment of conjunctival papillomas refractory to conventional modes of therapy.

Adult↗

Anterior segment and retinal pigmentary abnormalities in arteriohepatic dysplasia.

Arteriohepatic dysplasia (AHD, Alagille's syndrome) is presumed to be one of the six known familial intrahepatic cholestatic syndromes, all of which present with neonatal jaundice or failure to thrive, or both. Accurate early diagnosis of the proper syndrome is important, as arteriohepatic dysplasia has a good prognosis, whereas the other syndromes usually lead to death in infancy or early adulthood. Posterior embryotoxon was found in all five of our patients and may be one of the hallmarks of this syndrome. Axenfeld's anomaly was present in three of five patients, and retinal pigmentary abnormalities were found in four of five patients. Variable abnormalities were found in the cardiovascular system, bones, central nervous system, kidneys, endocrine system, and body habitus. Inheritance may be autosomal dominant as vertical transmission was documented in one family. Liver function improves during the first five years of life so that only the ocular and skeletal signs may be present in adults.

Abnormalities, Multiple↗