PubMed Health⌕ Search

Biomedical subjects

L T Chylack

Publications and source records attributed to L T Chylack.

At least 127 records · Page 7Linked to original sources
PubMed1981

Nonenzymatic glycosylation of bovine lens crystallins. Effect of aging.

We have investigated nonenzymatic glycosylation of crystallins from calf and mature bovine lenses (2-6 years old). The lens homogenates were treated with 200-fold molar excess of [3H]NaBH4 and the incorporation of radioactivity was determined. The extent of glycosylation was more precisely determined from the 6 N HCl hydrolysate of [3H]borohydride-treated proteins by analyzing the glucitol-lysine adduct on a high pressure cation exchange column. We found that the [3H]NaBH4 incorporation and the amount of glucitol-lysine detected increased with age, particularly in HM alpha crystallin, a high molecular weight aggregate which accumulates with aging. This age-related increase in nonenzymatic glycosylation was also demonstrated by a comparison of crystallins isolated from the cortex and nucleus of a single lens. Nonenzymatic glycosylation of lens crystallins exemplifies a new form of post-transitional modification of long-lived proteins in vivo.

Aging↗
PubMed1981

Age and the control of glycolysis in the rat lens.

Previous studies with lens dispersions indicated that the rate-limiting step in glycolysis shifts from hexokinase (HK) in the young lens to phosphofructokinase (PFK) in older lenses. Because the concentrations of the complex controlling factor for these enzymes could not be reproduced reliably in homogenates, the question of age-related control of glycolysis was re-examined in intact lenses. Toward this end, the levels of several metabolites of glucose were measured in fresh and incubated clear lenses. Of the substrates measured per fresh lens, only one changed significantly with age; fructose diphosphate was increased. When lenses were incubated in 2 to 12 mM glucose, the lactate production per lens was not significantly different with age. Together these results suggested that the glycolytic mass of the lens was constant with age. In both young and older lenses, increases in glucose in the medium led to increases in both glucose and glucose-6-phosphate in the lens. The lack of corresponding increase in lactate production suggested that the regulatory step lay downstream from HK, probably at PFK. This finding was corroborated by evidence that the initial acceleration of lactate production by the addition of cyanide (the Pasteur effect) was accompanied by decreases in the substrates of PFK, glucose-6-phosphate and fructose-6-phosphate. A secondary disinhibition of HK, as indicated by decreased lens glucose, became apparent after longer incubation with cyanide. This suggested that after disinhibition of PFK, HK became rate-limiting until the level of glucose-6-phosphate fell enough to allow the disinhibition of the latter enzyme as well. Thus PFK seemed to be the primary regulatory step in aerobic glycolysis in lenses of rats from 1 to 12 months of age.

Aging↗
PubMed1981

Supplementing glucose metabolism in human senile cataracts.

Assay of the activities of hexokinase, phosphofructokinase, and pyruvate kinase showed that the first two declined in aging human lens cortex and all three enzymes retained constant activities in the epithelium throughout life. Moreover, both clear and cataractous aging lenses contained the same enzyme activities. ATP contents in cataracts, however, were lower than in clear lenses; in fact, after incubation at 37.5 degrees C in isotonic (290 to 300 mOsm), glucose-containing media, ATP was rapidly lost from cataracts (but not from clear lenses), suggesting excessive ATP expenditure in cataracts for osmotic balance. Cataracts incubated in media containing either glucose-6-phosphate or fructose-1, 6-diphosphate produced significantly higher ATP than with glucose in the media, indicating that glucose metabolism in human senile cataracts could be supplemented with hexose phosphates. Fructose-1, 6-diphosphate appeared to be more efficient than glucose-6-phosphate in preventing lens swelling during incubation.

Adenosine Triphosphate↗
PubMed1981

The sorbitol pathway in the human lens: aldose reductase and polyol dehydrogenase.

The sorbitol pathway in human lenses is evaluated on the enzymic level. Adult lenses, normal and nondiabetic as well as diabetic cataracts, are found to contain limited levels of aldose reductase (AR) and high levels of polyol dehydrogenase (PD) relative to the animal lens. AR is confined primarily to the lens epithelium and is two to three times higher in juvenile lenses than in the adult lens. The level of AR in the epithelium of juvenile lenses is sufficient to cause significant osmotic stress. The Km of glucose of AR is roughly 200 mM, whereas the Km for NADPH is 0.06 mM. NADP inhibits human lens AR noncompetitively and has a Ki equivalent to the Km for NADPH. PD occurs in both the lens epithelium and cortex, remains persistently high with age, and decreases with increased cortical involvement. The Km of sorbitol for PD is 1.4 mM and for NAD is 0.06 mM. NADH (Ki 0.002 mM) competitively inhibits PD in the forward direction. PD purified 100-fold from diabetic and nondiabetic cataracts and normal lenses exhibit similar kinetic constants. PD has an extremely high Vmax in the fructose-to-sorbitol direction. The Km of fructose is 40 mM and for NADH is 0.02 mM. At high enough concentration, alrestatin also inhibits PD. The added activities of AR and PD in producing sorbitol and fructose in combination with decreased hexokinase with age may account for diabetic cataract formation in human lenses exposed to a high glucose stress. Nucleotide levels are reported for senile cataractous lenses.

Aging↗
PubMed1981

Studies on human cataracts. I. Evaluation of techniques of human cataract preservation after extraction.

The effects of several media and temperatures on the features (i.e. classification) of human cataracts have been studied with the aim of defining those storage conditions that least alter the appearance of the cataract after extraction. It was found that distilled water, normal saline, TC 199 medium with extra bicarbonate and 5.5 mM glucose, and silicone oil at 4 degrees, 36 degrees, and 37 degrees C are all unsatisfactory for preserving cataracts for more than 1 hr. Normal saline and TC 199 medium with bicarbonate and glucose are satisfactory for period not exceeding 30 to 60 min at 4 degrees C. The best set of conditions, one that leads to no significant change in the appearance of the cataract, is storage in a small covered glass vial at 4 degrees C with no added fluid. In this moist chamber, no significant changes in cataract classification occurred during a 4 hr period. The effect of -20 degrees C for 15 min on the appearance of a nuclear cataract was negligible, and it was concluded that lenses so treated could be used for a correlation between the nuclear cataract's CCRG classification and its light scattering properties, as studied in Parts II and III.

Cataract↗
PubMed1981

Studies on human cataracts. II. Correlation between the clinical description and the light-scattering parameters of human cataracts.

Eight lenses with nuclear cataracts have been classified. The light-scattering properties of the eight lenses were obtained with thin sections cut perpendicularly to the posterior-anterior axis. Analysis of the light scattering envelop in the I and I+ models yielded eight structural parameters that describe the density and orientation fluctuations. The variation of these parameters within each less corresponded well to the clinical description obtained from the stereoscopic photos.

Cataract↗
PubMed1981

Studies on human cataracts. III. Structural elements in nuclear cataracts and their contribution to the turbidity.

Gross correlation coefficient between light-scattering intensity and the optical parameters obtained for 48 sections of eight lenses with nuclear cataracts were evaluated. On the basis of these and other data in the literature, the structural elements, within the lens fiber are identified. These give rise to the optical parameters. It is proposed that three processes contribute to nuclear cataractogenesis: (1) syneretic process, (2) increase in the concentration but not in the size of protein aggregates, and (3) association (entanglement) between aggregates and optically anisotropic cytoskeleton or membrane components that leads to a decrease in structural bire-fringence.

Cataract↗
PubMed1981

Choroidal detachment. Clinical manifestation, therapy and mechanism of formation.

One hundred and twelve eyes of 103 patients were analyzed during a 9 1/2-year period after surgical drainage of a choroidal (ciliochoroidal) detachment (CD). Choroidal detachment in five groups of postoperative patients was studied. CD after surgery for cataract, for cataract and glaucoma, and for glaucoma alone had different time courses, but in all of these, there were similar amounts of protein (67% of plasma protein concentration) in the suprachoroidal fluid (SCF). In marked contrast was a group of patients with intraoperative choroidal effusions and very little protein (18% of plasma concentration) in the SCF. Identified also was a chronic recurrent form of CD that usually persisted for more than three months. Three distinct mechanisms by which choroidal effusion is formed were recognized, (1) one with evidence for the effusion occurring through an intact isoporous membrane (groups 1-3); (2) a second in which hemorrhagic SCF appeared acutely or subacutely (groups 1 and 2) through a disrupted isoporous membrane; and (3) a third form, an intraoperative choroidal effusion in patients with elevated episcleral venous pressure. Increased filtration rate of serum through an intact choriocapillary membrane caused molecular sieving of serum proteins. Inflammation, infection, cataract formation, and corneal edema were uncommonly encountered. Indications for surgery and recommended surgical technique are outlined in detail.

Biological Transport↗
PubMed1980

Differences in the susceptibility of various aldose reductases to inhibition. II.

The susceptibility of human lens aldose reductase (HLAR), human placental aldose reductase (HPAR), and rat lens aldose reductase (RLAR) to inhibition by 10 structurally diverse inhibitors is compared. Significant differences in the susceptibility of these enzymes was observed; however, no trends could be predicted. In general, HPAR appeared to be less susceptible to inhibition than either HLAR or RLAR, with the susceptibility of HLAR being more similar to RLAR than to HPAR. These findings indicate that the evaluation of aldose reductase inhibitors for potential clinical use may require the use of human aldose reductase from the appropriate target tissue.

Aldehyde Reductase↗
PubMed1980

Thiol oxidation in the crystalline lens. I. The rate-limiting role of hexokinase in aging rat and human lenses.

Reduction of nonprotein disulfides required both glucose or glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide phosphate (NADP). However, hexokinase (HK) was found to be the rate-limiting step: the glucose-supported reduction rate was only 50% of that of G6P-supported activity. This disulfide-reducing activity seemed to decline in the aging lens. Further, the glucose-supported activity dropped substantially if HK was deactivated with diamide; the deactivation was partially reversible. HK activity in aging clear and cataractous human lenses had greatly diminished. This might explain the disproportionate decrease in glucose-supported reduction in the aging lens. The components of the disulfide-reducing mechanism in human lens were reviewed and discussed.

Age Factors↗
PubMed1979

Posterior subcapsular cataracts: histopathologic study of steroid-associated cataracts.

Long-term steroid therapy is associated with production of a posterior subcapsular cataract (PSC). Five steroid-associated cataractous lenses were studied, using light, scanning, and transmission electron microscopy. Anterior, equatorial, and posterior regions were examined. Findings were compared with five age-matched senile PSCs and five nuclear cataractous lenses with no cortical opacities. The posterior polar region of steroid-associated cataractous lenses consists of (1) a superficial zone of liquefaction and (2) a deep zone of segmentally swollen lens fibers. Nucleated lens fibers are present in posterior cortical regions. Cytoplasm at knob and socket junctions had become lucent and plasma membranes were disappearing, leaving empty spaces. Laminated membranous configurations were seen. Although the same basic histopathologic abnormalities were found in steroid-associated cataracts and in nonsteroid senile PSCs, it is their organization and localization that may be the distinguishing characteristics of the steroid-associated cataract.

Adrenal Cortex Hormones↗
PubMed1979

Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels.

Rapid intraoperative choroidal effusion and flattening of the anterior chamber occurred during glaucoma filtering surgery in four young patients with prominent episcleral vessels, elevated episcleral venous pressure, and advanced open-angle glaucoma. Two of these four patients had Sturge-Weber syndrome. Intraoperative release of suprachoroidal fluid (SCF) through a posterior sclerotomy facilitated reformation of the anterior chamber and repositioning of the iris and ciliary body. Posterior sclerostomy performed prior to opening the anterior chamber minimized the above-mentioned untoward series of events. Analysis of SCF and serum demonstrated considerable differences in total protein and individual immunoglobulin levels; this appears to be a manifestation of molecular sieving at the level of the choriocapillaris. Choroidal detachment and postoperative serous retinal detachment are manifestation of this phenomenon.

Adult↗
PubMed1979

Efficacy of Alrestatin, an aldose reductase inhibitor, in human diabetic and nondiabetic lenses.

Immediately after cataract extraction, lenses from diabetic and nondiabetic patients were collected, classified, and assayed or incubated in high-glucose medium. The distribution of cataract types within the diabetic and nondiabetic groups was almost identical. The aldose reductase (AR) inhibitor AY22,284 (Alrestatin) was as effective in blocking sorbitol formation in diabetic as in nondiabetic lenses. While there was no difference in the level of intralenticular glucose, the diabetic lens produced significantly more sorbitol than did the nondiabetic lens. Also, the activity of polyol dehydrogenase (PD) was much lower in the diabetic population. The diabetic lenses swelled slightly more (P <.2) than nondiabetic lenses in high glucose media, and AY22,284 was effective in reducing the swelling of diabetic lenses in 35.5 mM glucose medium. While these results are preliminary, they suggest that diabetes, in some way, may confer on the human lens an increased susceptibility to osmotic stress via the sorbitol pathway. It is also reassuring to note that an AR inhibitor is no less effective in blocking the more active AR in the diabetic than in the nondiabetic lens. The therapeutic implications of this are discussed.

Aldehyde Reductase↗
PubMed1979

Dermatological and ocular examinations in rabbits chronically photosensitized with methoxsalen.

Four groups of female Dutch-belted rabbits (Oryctulagus cuniculus) were given methoxsalen (12 mg/kg) or placebo by oral intubation and 1 hr later were exposed to UVA for either 2 or 8 hr. This procedure was repeated 5 days each week for 18 mo. A fifth group received no drug and no UVA exposure. The skin of the animals given methoxsalen and UVA showed signs of acute and chronic phototoxicity. Multiple peripheral blood parameters of hepatic, renal and hematologic function were normal and were not different between groups. Complete ophthalmoscopic examinations were performed periodically. No cataracts were seen in any of the animals. This data provides the perspective that in one species the daily dose of methoxsalen and UVA required to induce chronic cutaneous photosensitization is lower than the daily dose required to induce cataracts. It is inadvisable to interpret this data as suggesting that no risk exists for patients being treated with oral methoxsalen photochemotherapy. The experimental evidence supporting photosensitization as a cause of cataracts and implicating a role of lens DNA in this cataractogenesis is reviewed. Because methoxsalen-UVA alterations of lens DNA or protein could lead to delayed onset of cataracts, and because of the serious nature and potential preventability of phototoxic lens opacification, appropriate protective eye wear is recommended for all patients receiving oral psoralen photochemotherapy.

Animals↗
PubMed1979

Thermal burns: the management of thermal burns of the lids and globes.

Our experience with 40 patients with eyelid and globe burns is reviewed. Initial emphasis should be placed on close monitoring, particularly of partially alert patients, debridement and treatment of corneal exposure with artificial tears and scleral shells when needed. The use of soft contact lenses in 2 patients with exposure was unsuccessful. Surgical treatment should be initiated when corneal exposure fails to respond to medical therapy. It is advisable to wait for the end stage of scarring so as to optimize chances for a single definitive correction. The use of retroauricular, supraclavicular or inner arm skin for grafting whenever possible is advised. The use of Frost sutures, tie-on dressings, and separate operations for upper and lower lids is recommended. Superficial wound sepsis is not a contraindication to grafting. Preoperative systemic or topical antibiotics do not seem to affect the outcome of the graft.

Adult↗
PubMed1978

Classification of human cataracts.

A stereoscopic system of lens photography was developed and was applied in the classification of different forms of cataract. Lenses, after surgical extraction, can be classified by a technician, independent of ophthalmological collaboration. This system meets the needs of the laboratory scientist and has been adopted by the Cooperative Cataract Research Group.

Cataract↗