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Biomedical subjects

L T Chylack

Publications and source records attributed to L T Chylack.

At least 145 records · Page 8Linked to original sources

Molecular sieving in suprachoroidal fluid formation in man.

Suproachoroidal fluid (SCF) obtained at the time of the surgical evacuation of a clinically significant choroidal detachment (CD) was analyzed for its chemical and cellular components in four distinct subgroups: (1) CD following cataract surgery, (2) CD (nonhemorrhagic) following glaucoma surgery, (3) CD (hemorrhagic) following glaucoma surgery, and (4) intraoperative CD during glaucoma surgery in patients with elevated episcleral venous pressure. The fluid obtained in groups 1, 2, and 4 was clear and slightly xanthochromic and contained low-molecular-weight substances in concentrations essentially equal to serum. Proteins and other high-molecular-weight substances were present in lesser amounts than in serum. Albumin, alpha1-antitrypsin, and transferrin were present in amounts approximately equal to those in serum, whereas alpha2-macroglobulin, IgM and IgG were decreased. beta-Lipoprotein and beta-complement were absent. It is postulated that this distribution of serum proteins is a manifestation of molecular sieving and is consistent with the existence of an isoporous membrane between the intravascular and suprachoroidal space with a pore diameter of 144 A. In the intraoperative choroidal effusions, there was evidence for exclusion of more of the lower, as well as all of the higher, molecular weight proteins. This suggested that the degree of molecular sieving increased with increasing filtration rate. In the hemorrhagic SCF, the distinctive character of the fluid and the protein concentrations indicated that the integrity of the capillary membrane was mardkedly disrupted, thereby allowing higher-molecular-weight proteins and cellular elements to enter the space.

Ascorbic Acid↗

Stability of mammalian lens phosphofructokinase.

Two interconvertible phosphofructokinase (PFK) forms were found in rat and human lenses; whereas only one predominant form was found in calf lens. PFK isolated from these lenses possessed a common property, i.e., pH-dependent cold (or acid) lability. The inactivation was prevented by including either adenosine triphosphate (ATP) or fructose-6-phosphate (fru-6-P) in the incubating media. The protective effect of ATP or fru-6-P was complete in rat or calf lenses. In human lens, although fru-6-P was fully protective, ATP protected only partially. The inactivation could be reversed by addition of fru-6-P, but not ATP, to the incubating media at 37.5 degrees C. Lens organ culture studies showed that the depletion of lenticular ATP seemed to precipitate the loss of PFK.

Adenosine Triphosphate↗

The ocular manifestations of juvenile rheumatoid arthritis.

We followed 210 cases of JRA closely for 14 years. Thirty-six patients (17.2%) developed iridocyclitis; it most frequently occurred in young females (0-4 years) with monarticular or pauciarticular form of the disease. In 30% of the patients iridocyclitis was first detected after 16 years of age. Forty-two percent had active iridocyclitis on entry. By combining quantitative antinuclear antibody titers with age, sex, and time on onset of arthritis, it has been possible to define the risk of developing iridocyclitis in individual patients. Our approach was effective in detecting iridocyclitis in new cases and exacerbations of the disease in established cases. Forty-four percent of patients with iridocyclitis had one or more identifiable early signs or symptoms. Iridocyclitis in 36% of patients did not respond to more than 6 months of intensive topical treatment with corticosteroids and mydriatics. Despite this statistic, patients had a better outcome than those experiencing the 50% incidence of blinding complications cited in earlier studies. Cataract and band keratopathy occurred in only 19% and 11% of our group, respectively. Only one case of chorioretinopathy was found in 173 patients who had received antimalarials; a significant number of posterior subcapsular cataracts were found in 75 patients who had received systemic corticosteroids. Keratoconjunctivitis sicca developed in 3 patients with iridocyclitis. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.

Adrenal Cortex Hormones↗

Properties of rat lens phosphofructokinase.

Two interconvertible forms of phosphofructokinase (PFK) have been eluted from a DEAE-cellulose column from the supernatant fraction of rat lens homogenates centrifuged at 96,000 x g for 1 hour at 0 to 4 degrees C. The interconversion can be manipulated by a change in the pH of the extracting and eluting buffers. PFK-I is the dominant form at pH between 7.4 to 7.05, while PFK-II dominates at pH 7.4 to 8.2. PFK-II is believed to be the functional form; it is inhibited by high concentrations of ATP and the inhibitory effect is enhanced by more acidic pH. Fructose-6-phosphate counteracts ATP inhibition, but the most potent de-inhibitors are ADP and AMP. Among the inorganic ions tested, sulfate, phosphate, ammonium, and potassium also de-inhibit, whereas calcium further inhibits the enzyme. The behavior of PFK under physiologic conditions and the significance of the presence of two forms of PFK in the lens are discussed.

Adenosine Triphosphate↗

pH-dependent temperature sensitivity of rat lens phosphofructokinase.

Rat lens phosphofructokinase (PFK) has been found to be cold-labile at acidic pH, even in the presence of sulfate and inorganic phosphate, two known positive effectors. The inactivation appears to be an irreversible process, but can be prevented by including ATP in the incubating media. The enzyme is relatively stable at pH 8.2 incubated at 0 to 4 degrees, 25 degrees, or 37 degrees C. in the absence of the effectors, but is extremely thermolabile if the pH is lowered to 7.30 or lower. The thermolability is counteracted by many effectors, among them sulfate and ATP are the most effective. The physiologic significance of PFK instability and effector protection in the lens are discussed.

Adenosine Triphosphate↗

Mechanism of "hypoglycemic" cataract formation in the rat lens. II. Further studies on the role of hexokinase instability.

In Part I1 of this study, the thermolability of lens hexokinase was implicated in the development of an experimental "hypoglycemic" cataract. After eight hours of glucose deprivation, there is a precipitous loss of lens hexokinase. This occurs approximately nine hours prior to the disorganization of the other enzymatic steps in glycolysis. Epithelial hexokinase, as an immediate response to glucose deficiency, shifts from the soluble to the insoluble phase. There is no such shift in the cortex-nucleus where only soluble hexokinase is found. After eight hours of glucose deprivation, both soluble and insoluble hexokinases throughout the lens undergo rapid deactivations. During the first eight hours of glucose deprivation the loss of lenticular ATP and K+ and the gain in wet weight can be reversed by restoring normal glucose levels; beyond eight hours the changes are irreversible. During the period of reversibility, hexokinase activity levels are normal; during the period of irreversibility hexokinase activity is 10 to 20 per cent of normal. Of the substances tested (mannose, galactose, fructose, glutamine, adenosine) only mannose could sustain the lens in the absnece of glucose. Neither endogenous free glucose nor glycogen could sustain the lens in the face of glucose deprivation. There appear to be no alternative exogenous or endogenous energy yielding substrates. The younger the animal, the more susceptible is its lens to glucose deprivation. This most certainly is a reflection of the increased susceptibility of younger lenses to osmotic stress, since lenses in each age group manifested similar changes in hexokinase activity, ATP, Na+, and K+ level.

Age Factors↗

Ocular manifestations of juvenile rheumatoid arthritis.

We followed 210 cases of juvenile rheumatoid arthritis closely for eleven years. Thirty-six of the 210 patients (17.2%) developed iridocyclitis. Iridocyclitis was seen most frequently in young female patients (0 to 4 years) with the monoarticular or pauciatricular form of the arthritis. However, 30% of the patients developed uveitis after 16 years of age. Although 61% of patients had a noncontributory ocular history on entry, 42% had active uveitis on entry. Our approach was effective in detecting uveitis in new cases and exacerbations of uveitis in established cases. Forty-four percent of patients with uveitis had one or more identifiable signs or symptoms, such as red eye, ocular pain, decreased visual acuity, or photophobia, in order of decreasing frequency. Even after early detection and prompt treatment, 41% of cases of uveitis did not respond to more than six months of intensive topical treatment with corticosteroids and mydriatics. Despite this, there was a dramatic decrease in the 50% incidence of blinding complications of uveitis cited in earlier studies. Cataract and band keratopathy occurred in only 22 and 13% of our group, respectively. We used chloroquine or hydroxychloroquine in 173 of 210 cases and found only one case of chorioretinopathy attributable to these drugs. Systemically administered corticosteroids were used in 75 of 210 cases; a significant number of posterior subcapsular cataracts was found. Typical keratoconjunctivitis sicca developed in three of the uveitis cases. This association with uveitis and JRA was not noted previously. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.

Adolescent↗

Mechanism of "hypoglycemic" cataract formation in the rat lens. I. The role of hexokinase instability.

Lenses from 100 gram albino rats remain clear and possess normal levels of Na+, K+, ATP, and hexokinase activity for 20 hours incubated in medium containing 12 mM glucose. Below 2.0 mM glucose, a cataract forms and there is an abrupt rise in lens Na+ and wet weight, a fall in lens K+, ATP, and hexokinase activity. The cataract is a thin lamellar opacity involving the anterior and posterior surfaces of the lens. If the lens is deprived of glucose for 48 hours, a nuclear cataract forms; the cortex between the superficial lamellar opacity and the nucleus being clear. This experimental cataract bears a striking resemblance to the hypoglycemic cataract seen in children. The thermal deactivation of hexokinase follows rapidly upon the depletion of its substrates (ATP and glucose) and is a primary factor leading to cataract formation. This was established by incubating the lens with 2-deoxyglucose, a competitive inhibitor of lens hexokinase. This compound blocks the entry of glucose into the glycolytic sequence. The cataract formed in its presence is identical morphologically and biochemically to that observed in a glucose-free medium. The effects of 2-deoxyglucose are prevented by increasing the glucose level; this rules out a direct toxic influence of 2-deoxyglucose and further supports the primary role of hexokinase thermolability in the etiology of this experimental cataract. This in vitro system appears to be an excellent experimental model for the study of the human hypoglycemic cataract.

Adenosine Triphosphate↗

The characterization of the hexokinases in several tissues of the calf eye.

Several tissues from the calf eye were studied so as to determine the characteristics of the hexokinases in each tissue. The corneal stroma, sclera, and vitreous body are devoid of measurable hexokinase activity. The tissue specific activities decrease in the following order: retina, ciliary body, corneal endothelium, lens capsule-epithelium, corneal epithelium, and lens cortex-nucleus. Each tissue possesses Types I and II hexokinase in varying proportions in the soluble and insoluble fractions; latent hexokinase is Type I in all tissues except the retina in which both Types I and II are found in the latent fraction. No hexokinase Type IIa, III, or IV is found in any ocular tissue. Michaelis constants for glucose and MgATP= are similar to those found in extraocular tissues. Except for retinal hexokinase, ocular hexokinases are quite similar to extraocular hexokinases. The activity of retinal hexokinase varies greatly and abruptly with time and with change in buffer composition; in the absence of Na2EDTA, glucose, and -SH compounds, there is a rapid deactivation of hexokinase and a shift of the soluble to the insoluble form. The relevance of these findings to glycolysis in each tissue is discussed.

Adenosine Triphosphate↗

Should tonometry screening be done by technicians instead of physicians?

A random sample of 768 clinic patients 40 years or older were screened by a technician utilizing Schlotz tonometry. All patients with an intraocular pressure of 20 mm Hg or more were referred for ophthalmological evaluation. The prevalence of frank glaucoma and suspected glaucoma in this infirm population was 1.8% and 2.5%, respectively. The cost of detecting frank or suspected glaucoma decreased in the second half of the study due to a decrease in the number of false-positive tests. These findings suggest that all clinic patients 40 years or older should be screened for glaucoma. Because many internists are reluctant to screen for glaucoma and because there are large number of false-positive tests by those who do tonometry episodically, we suggest that technicians do glaucoma screening.

Adult↗