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L T Chylack

Publications and source records attributed to L T Chylack.

At least 73 records · Page 4Linked to original sources

Strategies for measuring the rate of age-related cataract formation in vivo.

The Lens Opacities Classification System (LOCS II) has been tested as a method for detecting and grading longitudinal changes in cataract severity. The LOCS I and II systems have already been tested and validated for cross-sectional classification of human cataracts in vivo. 130 eyes (of 68 patients) were photographed at baseline and follow-up visits with Neitz CTR and Zeiss slit photography. The mean length of follow-up was 14.7 +/- 4.4 months. The severity of nuclear opalescence (NO), cortical (C) and posterior subcapular cataract (P) was graded in a masked fashion using the LOCS II standards. Side-by-side comparisons of baseline and follow-up photos were also done in a masked fashion to detect more subtle changes than might be evident in the LOCS II gradings. The annual percent progression in cataracts graded by LOCS II standards are: (NO): 12.4%, (C): 17.9%, and (P): 6.5%. The LOCS II standards are offered as a promising subjective method for longitudinal grading of human cataractous change in vivo.

Aged↗

Evaluation of a Lens Opacities Classification System.

A simple system, based on standard photographs, has been developed to classify lens opacities. The system allows the definition of cataract cases and noncases according to the location of lens opacification (nuclear, cortical, posterior subcapsular) and its extent (early or more advanced). Evaluation of the system has shown good to excellent reproducibility for clinical and photographic classifications. Comparisons of clinical and photograph-derived gradings has shown generally good agreement in classifying the presence and type of cataract; this agreement is highest for nuclear cataract. Photographic gradings of posterior subcapsular and, to a lesser degree, cortical opacities tend to underestimate the extent of opacification found by clinical gradings. The Lens Opacities Case-Control Study system is simple, reproducible, and easy to implement; it is offered for use in case-control and other cross-sectional studies of cataract with compatible classification goals.

Aged↗

Lens Opacities Classification System.

The Lens Opacities Classification System (LOCS) is a simple system for classifying age-related human lens opacities at the slit lamp or in retroilluminated and slit-lamp photographs. The system employs a set of standard Neitz CTR retroilluminated black-and-white photographs for classification of cortical and posterior subcapsular cataracts and a single color slit-lamp photograph for classification of nuclear color and opalescence. We present a detailed description of the system.

Cataract↗

Antioxidant status in persons with and without senile cataract.

The relationship between biochemical markers of antioxidant status and senile cataract was examined in 112 subjects aged 40 to 70 years. Seventy-seven of these subjects had a cataract in at least one lens. Antioxidant status was measured using erythrocyte superoxide dismutase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase activity, and indexes that included these enzymes plus plasma levels of vitamin E, vitamin C, and carotenoids. Subjects were grouped by level (low, moderate, or high) of the enzymes and antioxidant indexes. Results suggest that subjects with high levels of at least two of the three vitamins (vitamin E, vitamin C, or carotenoids) are at reduced risk of cataract relative to subjects with low levels of one or more of these vitamins (odds ratio, 0.2). The erythrocyte enzymes, either individually or in combination, did not appear to differ between subjects with and without cataract.

Adult↗

Glucose flux and the redox state of pyridine dinucleotides in the rat lens.

The concentration of alpha-glycerophosphate (GP) appeared to increase and readily reached a new steady state in lenses incubated with KCN or under hyperglucosic condition. This increase can be explained by the change in NADH/NAD ratio under each condition. The relative ratio of pyridine dinucleotides (NADH/NAD) was calculated from equilibrium equations of two NAD-linked enzymes, lactate dehydrogenase (LDH) and alpha-glycerophosphate dehydrogenase (GPDH). The change in NADH/NAD ratio based on biochemical assays correlates well with that estimated from GPDH reaction. This indicates that measurements of pyridine dinucleotides (e.g. in vivo redox fluorometry) can be used to demonstrate lens metabolic status.

Animals↗

Nutritional status in persons with and without senile cataract: blood vitamin and mineral levels.

As part of an exploratory study of nutrition and senile cataract relationships between biochemical markers of nutritional status and senile cataract were examined in 112 subjects aged 40-70 y. Seventy-seven subjects had a cataract in at least one lens. Blood levels were determined for total carotenoids, vitamin A, vitamin D, vitamin E, vitamin C, riboflavin, thiamin, vitamin B-6, zinc, copper, selenium, and magnesium. Subjects were grouped into quintiles for each nutrient. Logistic regression was used to estimate the odds ratios (ORs) for cataract among subjects in the highest quintile and the middle three quintiles relative to subjects in the lowest quintile. ORs were adjusted for age, sex, race, and presence of diabetes. Results suggest that risk of cortical cataract was reduced for subjects in the highest quintile of vitamin D and total carotenoids and that persons with cataract may have lower levels of vitamin C and higher levels of vitamin B-6 and Se.

Adult↗

Front surface fluorometric study of lens insoluble proteins.

Although the quantity of insoluble lens proteins increases with aging and cataracts, it is unknown whether the quality, such as protein structure, also changes correspondingly. In this study front surface fluorometry was used to study powdered samples of insoluble proteins isolated from young calf and old cow lenses, as well as from young clear and old cataractous human lenses. Tryptophan (Trp) fluorescence shows that there is a difference in protein conformation between young and old bovine samples. The old sample appears to have more open structure. This is demonstrated by a red shift in Trp emission maxima. The water-insoluble fraction shows 3-4 nm shift, while its urea-soluble and urea-insoluble fraction show 1-2 nm shift. The unfoldedness found in soluble crystallins is thus retained when they become insoluble. Both young and old human insoluble samples give a long Trp emission wavelength without showing any difference. Another major change that can be measured by fluorescence is the appearance of the 370/440 nm peak in old bovine insoluble powdered samples. Human samples also give this peak, and its position shifts to a longer wavelength in senile lenses.

Adult↗

Standardization and analysis of digitized photographic data in the longitudinal documentation of cataractous growth.

Age-related cataract formation in man can be documented with slit and retroillumination photographs. With digitization and image analysis of such photographs a cataract may be characterized by a frequency distribution of picture elements over a 255 step gray scale spectrum. Transition from a clear to a cataractous lens may be manifested as a change from a unimodal, Gaussian to a multimodal, non Gaussian frequency distribution respectively. How should one compare and contrast these two distributions, so to accurately describe the extent and significance of a change in lens opacification? The in vitro system of cold cataract formation in the rabbit lens was used as a model of the much slower process of age-related cataract formation in man. As in the human lens undergoing progressive opacification, the frequency distribution (number of pixels vs. intensity of gray) for a digitized image of a clear lens at 26 degrees C is unimodal and Gaussian; that of a fully developed cold cataract at 10 degrees C is multimodal and non-gaussian. In spite of the increasing multimodality of the frequency distribution as the temperature dropped and the cataract grew in density and size, the mean gray density proved to be a valid and useful measure to characterize the distribution and to compare different unaligned images. The Wilcoxon Rank Sum Test proved to be useless in comparing the frequency distributions from cataract images because it proved to be too sensitive to subtle changes in the degree of opacification. Anomalous behavior of the opacification process--i.e. clarification as well as opacification of the lens during cold cataract formation caused all pairs to appear statistically significantly different when in appearance there was no difference. The mean of the frequency distribution is less sensitive to this anomalous behavior and is useful as a comparative index. The method of calculating the threshold of significant change in the mean density of a cataract image is presented.

Animals↗

Lens hexokinase deactivation by near-UV irradiation.

Photodamage to lens hexokinase has been investigated by exposing the lenses of rat, rabbit and calf eyes to 300 nm irradiation. Hexokinase activity was diminished by 15.9% +/- 5.4 and 23.4% +/- 5.0 upon irradiation of the isolated rat lens for 1 and 2 hours respectively. Irradiation of the whole eye for 2 hours resulted in hexokinase deactivation of 13.6% +/- 5.8 and 19.2% +/- 6.2 for rat and rabbit lens homogenates and 55% +/- 7 for calf lens capsule plus epithelium. Enzyme deactivation was prevented when the isolated lens was irradiated with the vitreous attached. Glucose, catalase or ascorbate added to the medium prior to irradiation, each had a protective effect on hexokinase deactivation. The results are consistent with a mechanism in which photochemical generation of active species of oxygen, via the photosensitizing action of tryptophan photoproducts, plays a significant role in enzyme deactivation.

Animals↗

Progress toward developing a cataract classification system.

A cataract classification system is being developed based on a set of standard photographs. The system uses an ordinal scale ranging from 0 (no opacities) to 2 (definite opacities) to classify cataractous changes in the nuclear, cortical, and posterior subcapsular lens zones. The reproducibility of slitlamp-derived and photo-derived classifications using the system was evaluated. The reproducibility between 2 observers for slitlamp-derived classifications was very high (n = 60). The reproducibility within and among 4 photography readers was also good for photo-derived classifications (n = 100). Discrepancies were found between ratings derived from slitlamp examinations and from photographs; such discrepancies were most frequent for gradings of cortical opacities.

Cataract↗

Sources of variance in the objective documentation of human cataractous change with Topcon SL-45 and Neitz-CTR retroillumination photography and computerized image analysis.

In the application of Topcon SL-45 Scheimpflug slit and Neitz CTR retroillumination photography to in vivo documentation of cataractous change, several sources of variance affect the results of each technique. We have measured the between-person, between-photographer, between-focal plane (Neitz), between-photo session, replicate photograph (Topcon), between-image analyst and replicate image analysis variances encountered in in vivo documentation of human cataracts with the Topcon SL-45 and Neitz-CTR cameras and our system of computerized image analysis.

Adult↗

Quantitative detection of the molecular changes associated with early cataractogenesis in the living human lens using quasielastic light scattering.

We have used quasielastic light scattering to detect and quantitatively characterize the molecular changes associated with the early stages of cataractogenesis in the living human lens. The autocorrelation function of the fluctuations in the light scattered by the lens shows the presence of two major species responsible for the scattering. The first, fast diffusing species (f), has a diffusivity of approximately 3 x 10(-7) cm2/sec and corresponds to the alpha crystallin proteins. The second, slow diffusing species (s), has a diffusivity of approximately 10(-9) cm2/sec and corresponds to the diffusivity of a large aggregate. The intensity of light If and Is scattered into the collection optics by each of these species was also measured. We studied a group of 49 individuals ranging in age from 21 years to 82 years. In this group 40 presented with preoperative cataract development. In this patient population we found that regardless of age, or position in the lens that a plot of Itot = If+Is versus Is could be well fitted by a straight line with a slope less than unity and a positive intercept Ifo. It has been possible to explain this finding using a two state model for the molecular changes associated with early cataractogenesis. In this model the proteins in the slow diffusing species are aggregates each containing a definite number of rapidly diffusing proteins. The early development of cataract is represented by the redistribution of protein between the unaggregated form (f) and the aggregated form (s). The prediction for the relationship between Itot and Is based on this two state model is in very good agreement with our experimental data. Indeed the measured position of the point (Itot, Is) along this line provides a sensitive, and quantitative measure of the degree of cataract development at any selected location in the lens.

Adult↗

Spectroscopic study on the effects of nonenzymatic glycation in human alpha-crystallin.

Nonenzymatic glycated lens alpha-crystallin, isolated from human diabetic cataract lenses, does not differ in subunit size and secondary structure from nonglycated alpha-crystallin. The tertiary structure, however, has undergone a significant change as reflected in the changes of near-ultraviolet (UV) circular dichroism (CD) and fluorescence of intrinsic probes (tryptophan, nontryptophan) and extrinsic probes [(MIANS (6-(4'-maleimidylanilino)naphthalene-2-sulfonic acid) and TNS (6-(p-toluidinyl)naphthalene-2-sulfonate)]. A decrease in tryptophan fluorescence and an increase in nontryptophan fluorescence were observed for glycated alpha-crystallin. Decreased intensities of SH-specific fluorescent probes (MIANS) and hydrophobic probe (TNS) also were observed. The near UV CD and TNS polarization results suggest a more unfolded structure of the glycated crystallin. The significant decrease of sulfhydryl groups in glycated protein suggests that glycation facilitates a further secondary change.

Aged↗

Dynamic light scattering in the intact rabbit lens. Its relation to protein concentration.

The physical-chemical properties of highly concentrated protein systems as seen in the lens are poorly understood. Using the technique of dynamic laser light scattering spectroscopy, the authors have determined changes in the dynamics of lens proteins from the intact rabbit lens as a function of position and age. The authors have identified two heterogeneous populations of mobile scatterers with relaxation times of less than 0.5 msec and greater than 1 msec. A decrease in scattered light intensity at 90 degrees, an increase in protein concentration, and aging are associated with lengthening of the relaxation times of the less mobile population of scatterers. This data provides evidence for the existence of a gel-like structure of the lens proteins.

Aging↗

HLA-DP antigens in patients with pauciarticular juvenile rheumatoid arthritis.

The distribution of the recently described HLA-DP antigens was examined in a population of patients with pauciarticular juvenile rheumatoid arthritis and iridocyclitis, in an attempt to further characterize the immunogenetically determined susceptibility to this disease. There was a significantly increased frequency of the HLA-DPw2 antigen in the patients compared with the controls (67% versus 34%; odds ratio 3.9, P = 0.003 by Fisher's exact test). Population studies and family studies showed that this association with HLA-DPw2 was not secondary to linkage disequilibrium with the previously defined HLA-D region markers of disease (HLA-DR5 and HLA-DRw8) in these patients. These data raise the possibility that susceptibility to this form of juvenile rheumatoid arthritis may be regulated by more than one HLA-linked gene.

Arthritis, Juvenile↗

Non-enzymatic glycosylation in human diabetic lens crystallins.

Lens crystallins undergo non-enzymatic glycosylation with aging and diabetes mellitus. It is not known, however, whether all crystallins are subject to the same extent of glycosylation. Human diabetic lenses (approximately 80 years of age) were dissected into cortex and nucleus, then fractionated into various crystallins with gel chromatography (Sephacryl S-200, Sephadex G-75 or Bio Gel A-15m). The glycosylated crystallins were then separated from the nonglycosylated crystallins by affinity chromatography on Glyco Gel B boronic acid. The percentage of glycosylated crystallin was about 20-30%, and did not differ much among most crystallins, although gamma-crystallin has significantly less (p less than 0.01) glycosylated protein. The extent of glycosylation in the glycosylated crystallins, however, was found to be greater in the high molecular weight crystallins. The extent of glycosylation in alpha-crystallins is approximately two to four times that observed in beta- or gamma-crystallin. The extent of glycosylation appears to depend not only on the lysine content, which does not vary much among the crystallins, but also on the accessibility of the surface areas where lysine residues are located. This accessibility depends on the protein conformation and appears to correlate with protein unfolding.

Aged↗

Glucose metabolism by human cataracts in culture.

Metabolism in human senile cataracts has been studied using uniformly labeled [14C]glucose. Intracapsularly extracted lenses were cultured in TC-199 media with a glucose concentration of 5.5 mM. Results show that lactate production accounts for 97% of the glucose metabolized. Under these standard incubation conditions there is negligible accumulation of alpha-glycerol phosphate, glucose-6-phosphate, and sorbitol. The rate of lactate production was found to be relatively uniform over a range of cataract severities which were determined from the CCRG classification. The effects of several perturbants in the medium were measured. An ATP concentration of 3 mM was found to inhibit lactate production. Labeled glucose-6-phosphate in the medium was found to produce lactate at a rate approximately one half that of glucose. Elevated glucose concentration resulted in a slight decrease in lactate production and, in some lenses, production of a small amount of sorbitol. Overall, the glycolytic pathway appears to be functioning normally and without regard for cortical and nuclear opacification.

Adenosine Triphosphate↗