Biomedical subjects
E Cotlier
Publications and source records attributed to E Cotlier.
Cataract Image Analysis System.
A system for sequential colour video capture and analysis of lens opacities is described. A sensitive RGB (Red-Green-Blue) camera is coupled to a 486 DX2/66 IBM-compatible computer to obtain high-resolution images of cataracts. Vacuoles, retro-dots, suture opacities, wedge opacities, cortical and posterior subcapsular opacities and nuclear sclerosis can be digitised and subjected to various analysis systems and colour prints obtained. The size and number of vacuoles and opacities can be determined by selecting areas of interest, and line tracings of whole lens, isolated opacities or nuclear sclerosis can be separated by analysis into 16.8 million plus colour gradients. The Cataract Image Analysis System represents a precise and new digitised procedure for cataract documentation and may be of value in determining cataract progression and evaluation of medical therapy.
Phacoemulsification by residents.
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Camel lens crystallins glycosylation and high molecular weight aggregate formation in the presence of ferrous ions and glucose.
The incubation of camel lens cortex homogenate with 100 microM ferrous ions and 5.5 mM glucose under sterile conditions caused rapid protein aggregation, but little or no reaction was seen with either 100 microM ferrous ions or 5.5 mM glucose alone. The formation of glycosylated high molecular weight (HMW) protein aggregates was confirmed by light scattering studies, a decreased level of free -SH groups, incorporation of [14C]-glucose and elution of HMW protein aggregate just after the void volume of a Sephacryl S-1000 column. The bonding involved in the formation of these aggregates was found to be mainly disulfide in nature. Isoelectric focusing (IEF) in the presence and absence of reducing conditions indicated that gamma-crystallins may be involved in the formation of HMW protein aggregates. The modifications observed were found to mimic those seen in cataractous lenses.
Aspirin prevents the nonenzymatic glycosylation and carbamylation of the human eye lens crystallins in vitro.
When the human eye lens homogenate which was incubated with [14C]-acetylsalicylic acid (aspirin) and separated into alpha-, beta-, and gamma - crystallins by Sepharose 6B gel-filtration, the radiolabel was found in all the three crystallins. The significant decreases in the free zeta-amino groups of aspirin treated crystallins as compared to the untreated ones indicate the probable sites of acetylation in the crystallins. The inhibition of the binding of [14C]-glucose and [14C]-cyanate to the aspirin pre-treated crystallins suggests that prior acetylation with aspirin prevents the occurrence of the nonenzymatic glycosylation and carbamylation of the lens crystallins in vitro.
Retinoblastoma: the Saudi Arabian experience.
During the period March 1983-May 1987, 74 cases of retinoblastoma were evaluated at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. 60% of the cases were unilateral with a female preponderance of 59.4% noted for this series. Additionally, the mean age at diagnosis was 22 months, and delay of retinoblastoma diagnosis since the first symptoms were observed ranged from two days to 36 months. Fifty-seven eyes were enucleated, and in 21 of these patients, this was the sole form of therapy. The remainder of patients were treated with radiotherapy alone or combined with chemotherapy, cryotherapy/photocoagulation. Overall, two-year survival statistics of this group of Saudi patients is 80% which compares favorably to other reports in the West. Emphasis is placed on management of the retinoblastoma patients by a multi-disciplinary group, and public educational efforts are imperative.
Rise in lens temperature on exposure to sunlight or high ambient temperature.
The effect of increase ambient temperature and sunlight on the temperatures of the rabbit lens and posterior chamber (PC) aqueous humour was measured by needle thermistor probes while the rectal temperature was monitored. Exposure of rabbits to sunlight (35 degrees-42 degrees C), in New Haven, Connecticut, USA, resulted in significant temperature increases in PC (4.3 degrees C), lens (3.2 degrees C), and rectum (2.3 degrees C). Returning animals to the shade resulted in a progressive decrease in the temperatures of the PC or lens in the tested eye, but repeating exposure to sunlight resulted in significant increases of the baseline (PC) temperature (increase 2.68 degrees C) of the second eye. Exposure of rabbits to sunlight at 49 degrees C in Chandigarh, India, resulted in increased PC temperature of 4.48 degrees C after 9 minutes. Increased PC and lens temperatures after exposure to sunlight are due both to an ambient temperature effect through the cornea and to increased body temperature. In dry and hot tropical areas of the world temperature increases in the lens after exposure to sunlight may initiate or accelerate the formation of senile cataracts.
Cohen syndrome with bull's eye macular lesion.
The Cohen syndrome is an autosomal recessive disorder which is characterized by hypotonia, obesity, mental deficiency, and facial, oral and ocular anomalies. During a twelve-year period of observation, the authors' patient manifested pigmentary retinal degeneration and a bull's eye macular lesion. The Cohen syndrome must be included in the differential diagnosis of syndromes with retinitis pigmentosa.
Free epsilon amino groups and 5-hydroxymethylfurfural contents in clear and cataractous human lenses.
The free epsilon-amino groups and 5-hydroxymethylfurfural (5-HMF) contents were determined in soluble and insoluble proteins of clear human lenses and diabetic and nondiabetic senile cataractous lenses. The free epsilon-amino group content of soluble proteins in diabetic cataracts was decreased by 37% (P less than 0.01), whereas in nondiabetic senile cataracts it did not differ from that of clear lenses. The free epsilon-amino group content of insoluble proteins both in diabetic and nondiabetic cataracts was decreased significantly (P less than 0.001, P less than 0.015, respectively). The 5-HMF content of soluble proteins in diabetic cataracts was increased by 52% (P less than 0.001), whereas in nondiabetic cataracts it did not change from that of clear lenses. The 5-HMF content of insoluble proteins in diabetic as well as in nondiabetic cataracts was increased significantly as compared to that of clear lens (P less than 0.001, P less than 0.001, respectively). The soluble protein of diabetic and nondiabetic cataracts was decreased with an increase in the insoluble protein content. These results suggest that nonenzymatic glycosylation plays a role in the conformational change of lens proteins in both diabetic and nondiabetic cataracts.
Acetylation of lens crystallins: a possible mechanism by which aspirin could prevent cataract formation.
The calf eye lens homogenate incubated with [1-14C-acetyl] aspirin and separated into HMW, alpha, beta H, beta L and gamma-crystallins by means of Sepharose 6B and Bio-Gel P2 columns showed radioactivity in all the crystallins. In contrast, no radioactivity was found in the crystallins when the lens homogenate was incubated with [14C-carboxyl] aspirin. These experiments clearly indicated that the eye lens crystallins are acetylated with aspirin. Furthermore, no decrease in the radioactivity in the crystallins after exhaustive dialysis against 0.15M NaCl suggests a covalent type of binding of acetyl moiety of aspirin to the lens crystallins. The significant decrease in the free epsilon-amino groups of aspirin-treated crystallins further suggests the probable sites of acetylation in the crystallins. It may be concluded that acetylation of free epsilon-amino groups of lens crystallins by aspirin may confer protection against crystallin aggregation in cataractogenesis.
Serous retinal detachments in thrombotic thrombocytopenic purpura.
Serous retinal detachments are a rare ocular complication of thrombotic thrombocytopenic purpura (TTP), with only six previous case reports in the literature. We have recently observed two patients with relapsing TTP who developed bilateral serous retinal detachments during acute exacerbations of their disease. In contrast to all but one of the previously described patients, both of our patients survived the episode during which retinal detachments occurred. Hypertension appears to contribute to the development of retinal detachments in TTP, and vigorous efforts at blood pressure control are indicated. Serous retinal detachments may be a more frequent component of chronic relapsing TTP than has been suspected.
Enzymatic activity of quinonoid dihydropterin reductase and tetrahydropterin content in human ocular tissues and senile cataracts.
The quinonoid dihydropterin reductase (DHPR) activity and tetrahydropterin content were determined in human ciliary body--iris, retina, normal lens and senile cataracts. The DHPR activity was higher in the retina [120.56 +/- 12.46 nmol NADH oxidized min-1 (mg soluble protein)-1] than in the ciliary body--iris [46.10 +/- 7.46 nmol NADH oxidized min-1 (mg soluble protein)-1] and lens [2.79 +/- 0.15 nmol NADH oxidized min-1 (mg soluble protein)-1]. In the distribution of DHPR activity in the lens, the capsule-epithelium showed 1.5 and 10 times more activity than the cortex and nucleus, respectively. The apparent Km values for each of the substrates of DHPR activity in lens were obtained by Lineweaver--Burke plots. The plots. The tetrahydropterin content was found to be higher in the retina [826 +/- 76 pmol (g protein)-1] than in the ciliary body--iris [584 +/- 48 pmol (g protein)-1] and lens [82 +/- 16 pmol (g protein)-1]. The DHPR activity and tetrahydropterin content were decreased significantly in senile cataracts as compared with the values of age-matched clear lenses. The importance of the DHPR activity in the maintenance of tetrahydropterin in its reduced form in ocular tissues is discussed.
Glucocorticoid-lens protein adducts in experimentally induced steroid cataracts.
The injection of glucocorticoids into the vitreous chamber of the rabbit eye results in the development of posterior subcapsular opacities. These lesions appear to be similar in morphology to human steroid-induced cataracts. Electron microscopic analysis revealed fiber cell separation, vacuolization, and changes within the matrix of the crystallins. Opacification could only be produced by glucocorticoids possessing a reactive C-20,21 hydroxylcarbonyl function, supporting the hypothesis that glucocorticoid addition products are involved in the induction of these lesions. The occurrence of glucocorticoid-lens proteins adducts was confirmed by tritium incorporation and by radioimmunoassay of protein hydrolysates obtained from these lenses.
The enzymatic activities of GTP cyclohydrolase, sepiapterin reductase, dihydropteridine reductase and dihydrofolate reductase; and tetrahydrobiopterin content in mammalian ocular tissues and in human senile cataracts.
The enzymatic activities of GTP cyclohydrolase, sepiapterin reductase, dihydropterin reductase and dihydrofolate reductase were determined in the ocular tissues of rat, rabbit, calf and human. The enzymatic activities of the pteridine biosynthesis and the content of tetrahydropteridine (BH4) were higher in retina and ciliary body-iris as compared with lens tissue in all mammalian species tested. The activities of the pteridine synthesizing enzymes and BH4 content were decreased in human senile cataracts as compared with age-matched clear human lenses. The loss of BH4 may result in lenticular proteins more susceptible to oxidation and contribute to high molecular weight protein formation in cataracts.
A carrier state of X-linked juvenile retinoschisis.
The carrier state of X-linked juvenile retinoschisis has not been known to be associated with any fundus abnormalities. We report a case where there are funduscopic changes and mild visual acuity changes in one eye of a carrier.
Anophthalmos and first branchial arch defects.
The association of unilateral mandibulofacial dysostosis and anophthalmos at the same side is reported. The proband presented at the age of six months with: right anophthalmos and hypoplasia of the orbit at the same side, hypoplasia of the right mandible and maxilla, right external ear deformity, cyanotic heart disease, hemivertebrae, cataract and corneal opacity in the left eye. This case shows the maximal effect of the abnormal development of the first branchial arch (the mandible, maxilla, and ears) on the globe and the orbit. The other end of the spectrum in which the minimal effect on the globe was present (unilateral absence of choriocapillaris and retinal pigment epithelium inferiorly) was reported by Cotlier & Alghadyan in 1981. This supports the concept that abnormal development of the mandible may influence the development of the orbit and the globe. The extent of the influence of the abnormal developing first branchial arch on the eye is discussed.
Biosynthesis of neopterin, sepiapterin, and biopterin in rat and human ocular tissues.
Neopterin, sepiapterin, and biopterin synthesis by lens, retina, and ciliary body-iris of rat and human indicates pteridine formation from their precursor, GTP. The pteridine biosynthesis was higher in the retina (neopterin 422 +/- 27, 260 +/- 24; sepiapterin 135 +/- 12, 118 +/- 14; biopterin 76 +/- 10, 68 +/- 8 nanomoles/g soluble protein/hr, in rat and human, respectively) than in the ciliary body-iris and lens. The light-sensitive pteridines may protect eye tissues against the effects of sunlight in addition to their role in the hydroxylation of aromatic amino acids.
Ornithine delta-aminotransferase activity in retina and other tissues.
Ornithine delta-aminotransferase (OAT) activity was determined in liver, kidney, brain, retina and ciliary body-iris of rat, rabbit, calf and human. OAT activities (nanomoles delta 1-pyrroline-5-carboxylate/mg protein/hr) in retina were (mean +/- SE) 324 +/- 43, 240 +/- 24, 234 +/- 26 and 218 +/- 22 respectively in rat, rabbit, calf and human. The OAT activities in retina were three times higher than in brain and 80% of that of liver. 2-oxoglutarate was the preferred amino acceptor substrate for OAT activity. In rat retina the activities of OAT with glyoxalate, beta-hydroxypyruvate, pyruvate, and oxaloacetate were 51, 44, 30, and 30% of that of 2-oxoglutarate respectively. A lack of substrate OAT specificity indicates OAT deficiency such as occur in gyrate atrophy of the choroid and retina could impair metabolism of ketoacids. A candidate for possible toxicity to the retina in OAT deficiency is glyoxalate. Arginine glycine transamidinase activity was not detectable in human retina, thus a previously postulated creatine phosphate deprivation in OAT deficiency may not be applicable to the pathogenesis of the disease.