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Biomedical subjects

L T Chylack

Publications and source records attributed to L T Chylack.

At least 109 records · Page 6Linked to original sources
PubMed1984

Inherited predisposition to iridocyclitis with juvenile rheumatoid arthritis: selectivity among HLA-DR5 haplotypes.

HLA-DR5 is associated with a chronic iridocyclitis and juvenile rheumatoid arthritis with onset in early childhood. Previously published data provided indirect evidence for selective linkage between two HLA-B alleles and HLA-DR5. To test this observation further, 38 families, the probands of which have chronic iridocyclitis and juvenile rheumatoid arthritis, were HLA typed so that haplotypes associated with disease could be established. HLA-DR5 was linked to HLA-Bw44 or to HLA-Bw35 and to HLA-Cw4 in the majority of haplotypes obtained in the probands. Both HLA-Bw44, -DR5 and HLA-Bw35, -Cw4, -DR5 occurred more commonly in the proband haplotypes than in the control haplotypes. The frequency of the haplotype HLA-Bw44, -DR5 was 0.133 compared with 0.007 (X2 = 27.04, P less than 10(-6] and for HLA-Bw35, -Cw4, -DR5, it was 0.093 compared with 0.11 (X2 = 13.83, P = 0.0002). The relative risks were 20.77 and 9.23, respectively, versus 3.52 for HLA-DR5 alone. HLA-Bw44 occurred much more commonly in proband HLA-DR5 haplotypes (0.455) compared with control HLA-DR5 haplotypes (0.067) (X2 = 8.26, P less than 0.01). Not all HLA-DR5-bearing haplotypes predisposed equally to chronic iridocyclitis and early-onset pauciarticular juvenile rheumatoid arthritis.

Arthritis, Juvenile↗
PubMed1984

Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus.

We have examined the nonenzymatic glycation of human lens crystallin, an extremely long-lived protein, from 16 normal human ocular lenses 0.2-99 yr of age, and from 11 diabetic lenses 52-82-yr-old. The glucitol-lysine (Glc-Lys) content of soluble and insoluble crystallin was determined after reduction with H-borohydride followed by acid hydrolysis, boronic acid affinity chromatography, and high pressure cation exchange chromatography. Normal lens crystallin, soluble and insoluble, had 0.028 +/- 0.011 nanomoles Glc-Lys per nanomole crystallin monomer. Soluble and insoluble crystallins had equivalent levels of glycation. The content of Glc-Lys in normal lens crystallin increased with age in a linear fashion. Thus, the nonenzymatic glycation of nondiabetic lens crystallin may be regarded as a biological clock. The diabetic lens crystallin samples (n = 11) had a higher content of Glc-Lys (0.070 +/- 0.034 nmol/nmol monomer). Over an age range comparable to that of the control samples, the diabetic crystallin samples contained about twice as much Glc-Lys. The Glc-Lys content of the diabetic lens crystallin samples did not increase with lens age.

Adolescent↗
PubMed1984

Direct measurement of polyol pathway activity in the ocular lens.

A method to measure the polyol pathway metabolic flux in the intact rabbit lens by 13C nuclear magnetic resonance spectroscopy is described. In the lens exposed to 35.5 mM glucose, the polyol pathway accounts for 1/3 of the total glucose turnover. The high metabolic activity of the pathway suggests a significant alteration in the reduced to oxidized pyridine nucleotide ratio in the lens exposed to high glucose.

Animals↗
PubMed1984

Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) method: II. Staged simplification of cataract classification.

One thousand nine hundred and seventy-six cataracts extracted intracapsularly were classified according to the system adopted by the Cooperative Cataract Research Group (CCRG) Consortium. A nine-stage protocol for simplifying the classification data is presented. The method of simplifying the basic CCRG classification emphasizes anatomic similarities among lenses. Simplification is indicated when small numbers of cataracts in any class provide insufficient statistical power to allow detection of scientifically or clinically important differences in rates between comparison groups, if such differences exist; however, simplification unavoidably obscures the anatomic, biochemical, and biophysical features of individual cataracts. Age-specific characteristics of this population of 1976 cataracts are used to demonstrate the effects of the simplification process. The preponderance of mixed cataracts and the relative scarcity of pure cataracts are documented, and the implications of these numbers for cataract research are presented.

Age Factors↗
PubMed1984

Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) method: III. The association of nuclear color (sclerosis) with extent of cataract formation, age, and visual acuity.

Nineteen hundred and seventy-six immature human cataracts extracted intracapsularly were classified according to the Cooperative Cataract Research Group (CCRG) method of cataract classification. Data on cataract location and extent, nuclear color, preoperative visual acuity, age, and sex were organized and stored in the PROPHET system. The data were examined for relationships between nuclear color (sclerosis) and the age of the cataractous lens, the extent of opacification in seven anatomical regions including the degree of nuclear opacification and the preoperative visual acuity. Nuclear color correlates with age in a curvilinear manner. Nuclear yellowing increases gradually with increasing nuclear opacification, but the color change is so slight as to be useless for the purposes of inferring the intensity of nuclear opacification from the color of the nucleus. There is no association between the extent of anterior cortical, equatorial cortical, posterior cortical, subcapsular or supranuclear opacification, and nuclear color. Nuclear color impairs vision only for the range dark yellow through black. These data justify the recommendation that nuclear color be abandoned as the single index of the severity of any type of senile cataractous change.

Age Factors↗
PubMed1983

Early-onset pauciarticular juvenile rheumatoid arthritis. A histopathologic study.

A young girl with early-onset pauciarticular juvenile rheumatoid arthritis suffered from recurrent severe bilateral iridocyclitis. Despite intensive medical therapy, she gradually lost all useful vision and ultimately required bilateral enucleation at the age of 10 years for control of pain and photophobia. Histopathologic study of the eyes revealed in the iris and ciliary body a dense inflammatory infiltrate composed principally of plasma cells, as well as angle closure, a dense cyclitic membrane, retinal detachment, cystoid macula, and optic atrophy. Immunoperoxidase stains showed little immunoglobulin within or around the plasma cells within the ciliary body, although strong reactions for IgG and kappa- and lambda-light chains were seen in other parts of the eyes.

Arthritis, Juvenile↗
PubMed1983

Response of the lens to oxidative-osmotic stress.

Both aldose reductase and glutathione reductase share a common cofactor, NADPH. Glutathione reductase is preferentially activated due to its higher affinity for the cofactor. Since NADPH is primarily consumed by glutathione reductase, which in conjunction with glutathione peroxidase detoxifies H2O2 present in the aqueous humor, the cataractogenic role of sorbitol-induced osmotic pressure must therefore depend on the availability of NADPH for aldose reductase activity. We examined the response of the lens to an oxidative-osmotic double stress and found that the lens indeed produced 79% less sorbitol and 45% less fructose than a lens subjected to the osmotic stress alone. Morphological studies showed that photo-oxidation damaged the epithelium where the cation pump resided. However, with additional osmotic stress, the swelling of lens fibers in the posterior pole region became more pronounced, and cell nuclei deep in the lens nuclear bow were dislodged to the posterior pole. This could be explained by the slight but significant loss of K+ in the lenses under the double stress. Apparently, the slightly decreased 86Rb uptake (26% loss), caused by photooxidation could not maintain adequate ionic balance even though the stress from accumulation of sorbitol + fructose was sub-maximal. No disturbance in the glycolytic activity or to the 86Rb efflux was found in these lenses, however.

Animals↗
PubMed1983

GSSG-reducing activity in lenses deficient in glucose-6-phosphate dehydrogenase.

Steroids that inhibit glucose-6-phosphate dehydrogenase (G6PD) were used to examine the correlation between the loss of GSSG-reducing activity and G6PD deficiency in the lens. The correlation was found to be nonlinear. In senile cataracts, which had lost 36% of NADPH-generating activity as compared to clear lenses, the estimated loss of GSSG reduction was only 20%. On the other hand, lenses with severe G6PD deficiency (i.e. 93% loss) retained at least 28% GSSG-reducing activity. The declined reducing activity, however, suggested a possible role of G6PD deficiency in cataract formation in young patients.

Adult↗
PubMed1983

The effect of freezing on human cortical cataracts.

To ascertain a direct relationship between the light scattering intensity and the particle scattering the light, thin (6-20 micrometers) sections were cut from frozen human cataracts. Freezing for 15 min (-10 C) and then thawing had no effect on the clarity or light scattering properties of nuclear cataracts. Cortical cataracts treated in the same manner appeared to be much clearer than they were prior to freeze-thawing. Light scattering measurements were obtained as a function of scattering angle, both in the I parallel and I perpendicular mode; a He-Ne laser was used. Results showed a reduction in the light scattering intensity in the I parallel and I perpendicular modes with repeated cyclical freezing and thawing and that this decrease was most pronounced at higher scattering angles. Morphologic data showed that much of the anatomical heterogeneity present in the human cortical and rat lens osmotic cataract disappeared upon freeze-thawing. However, even though the anatomical heterogeneity was less, there was persistence of serious cellular anatomical disorganization in grossly transparent parts of the cortex. This suggests that transparency is not dependent upon the presence of intact fiber cells. The importance of these findings to studies of light scattering, cataract classification and analysis of cryoextracted human lenses is discussed.

Animals↗
PubMed1983

Classification of human senile cataractous changes by the American Cooperative Cataract Research Group (CCRG) method. I. Instrumentation and technique.

The American Cooperative Cataract Research Group (CCRG) has adopted a system of classifying human cataractous changes that is based on separate and independent photographic documentation of opacification and nuclear color. This system has been extremely useful to the laboratory scientist who wishes to know the significance of associations between laboratory data and the extent or type of cataractous change. It has been applied to the analysis of nearly 2500 cataracts since 1976. This study presents the details of the instrumentation and technique of this new system and the results of classifying 2231 intracapsularly-extracted cataracts.

Aged↗
PubMed1983

Phase separation in rat lenses cultured in low glucose media.

Experimental evidence that indicates the nuclear opacity that develops in the hypoglycemic cataract in rat lenses is the result of a phase separation of the lens cytoplasm is presented. Phase diagrams of the cytoplasm of organ-cultured lenses were constructed for a series of incubation times in normal and hypoglycemic media. In normal media, the maximum phase separation temperature, Tmax, of the lens cytoplasm decreases with time. In hypoglycemic media, Tmax increases with time and exceeds 37 C after 24 hrs. The increase in Tmax can be stopped and reversed if the lens is returned to normal media within 8 hrs; in good agreement with an earlier biochemical analysis of the kinetics of hypoglycemic cataract formation.

Animals↗
PubMed1983

Calcium-containing opacities in the human lens.

Cooperative Cataract Research Group (CCRG) photographic procedures developed by Chylack have made it possible to localize and analyze specific lens opacities for their ultrastructural and chemical characteristics. One group of human lens opacities has been shown to have a high phosphorus/sulfur ratio (as compared to normal lens fiber cells) and an accumulation of unit membranes. The present paper describes another variety of human lens opacity with the following characteristics: (1) high calcium, low sulfur, undetectable phosphorus, as determined by Energy Dispersive X-ray Analysis (EDXA) of bulk specimens in the scanning electron microscope (SEM), or "thick" sections with the transmission mode of the SEM; (2) spheroidal shape; (3) up to approximately 300 microns in size; and (4) birefringence. Microchemical analysis of these opacities shows that the calcium is in the form of calcium oxalate. These calcium-containing opacities, which have been detected in 14 out of 406 human cataractous lenses, have a characteristic morphology, as seen in the CCRG stereo photographs. Therefore, the presence of these calcium opacities, if not obscured by other kinds of opacities, can be detected with a high degree of accuracy in the fresh lens from the CCRG photographs alone.

Calcium↗
PubMed1982

Depletion of sorbitol and fructose from young and older rat lenses.

Fasting for as little as 24 hr markedly reduced the levels of sorbitol and fructose in the adult rat lens. This depletion was found in both young (1 month) and older (8-12 month) rats. Two modes of depletion were examined: decreased synthesis and metabolic breakdown. The role of diffusion was discussed. In vitro experiments showed that in both age groups, decreased glucose in the medium resulted in a proportional decrease in glucose and sorbitol in the lens; the lenticular fructose level was not changed. In contrast to reports showing decreased glycolysis with age, the sorbitol-synthetic capacity of rat lenses was undiminished with age. Acceleration of glycolytic flux in lenses in vitro resulted in decreases in fructose, and to a lesser extent in sorbitol, in both age groups. These findings indicated that fructose can be removed from lenses by metabolism; and that, especially in the older lenses, glycolysis may represent a major route by which fructose, and hence sorbitol, are eliminated during fasting.

Animals↗
PubMed1982

Nanophthalmos with uveal effusion: clinical and embryologic considerations.

Three brothers were found to have nanophthalmos as evidenced by marked hyperopia, decreased global axial length, and shallow anterior chambers. The thickness of the lens, measured with A-scan ultrasound biometry in two cases, was much greater than normal. Choroidal thickening with shallow retinal detachments without breaks was found in those patients. Fluorescein angioscopy demonstrated leaks beneath the serous retinal detachments in one. The spontaneous presence of choroidal effusions and retinal detachments in nanophthalmic patients has been reported only rarely. The present findings emphasize that careful examination of the posterior segment should be done prior to anterior segment surgery in these patients to alert the surgeon to the possibility of serious intra- and post-operative choroidal effusions and retinal detachments. An attempt is made to explain some of the clinical findings in nanophthalmos by extrapolating from results obtained on experimental animals. It is postulated that the increased lens size in nanophthalmos may be due to the abnormal accumulation of a factor influencing lens fiber differentiation. The overall small size of the eye may be the result of the formation of a smaller than usual optic vesicle anlage.

Aged↗
PubMed1982

Cataracts in the exfoliation syndrome (fibrillopathia epitheliocapsularis).

The histopathological features of the lenticular part of the exfoliation syndrome includes active production of pathological capsular substance in the epithelial cells in the zona germinativa. Analysis of the cataract pattern of 431 exfoliation lenses and 1776 control lenses extracted at the Massachusetts Eye and Ear Infirmary shows a significant difference. Cortical and supranuclear cataract is less common and severe in the exfoliation syndrome, while the reverse is true for nuclear cataract. Posterior subcapsular cataract shows no difference while the anterior variety is slightly more common in the control group. It is suggested that the high level of epithelial metabolic activity may be beneficial for the ionpumps and electrolyte environment of the cortical fibres.

Basement Membrane↗
PubMed1982

13C-nuclear magnetic resonance studies of sugar cataractogenesis in the single intact rabbit lens.

In this report we demonstrate that 13C-nuclear magnetic resonance spectroscopy may be used to monitor the sorbitol and glycolytic pathways in a single, intact, crystalline lens of the rabbit, thereby providing a new, noninvasive method for the study of sugar cataractogenesis. This approach is particularly useful for the measurement of intralenticular metabolic fluxes in single lenses under various conditions, at a time resolution previously unavailable in lens biochemistry.

Animals↗