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Biomedical subjects

Z Friedman

Publications and source records attributed to Z Friedman.

At least 19 recordsLinked to original sources
PubMed1992

[Pneumatic-retinopexy scleral buckling for retinal detachment].

30 eyes with rhegmatogenous retinal detachment due to retinal tear at the upper half of the circumference or due to a macular hole underwent SF6 gas injection into the vitreous. In 25 eyes (83%) the retina had re-attached 1-2 days following the injection and the tear was then photocoagulated. Final visual acuity was 6/12 or better in 13 eyes, 6/15-6/20 in 4 eyes, 6/30-6/60 in 8 eyes and less than 6/60 in 5 eyes, 3 of which had a macular hole. There was no morbidity or irritation compared to conventional scleral buckling, and the functional results were better. 4 of the 5 failures underwent successful surgery. In only 1 eye the retina could not be attached by surgery. Pneumatic retinopexy can substitute for surgery in selected cases of retinal detachment.

Gases↗
PubMed1991

Human retinal pigment epithelial cells possess V1 vasopressin receptors.

Membrane preparations of cultured human retinal pigment epithelial (RPE) cells were incubated with various concentrations of [3H]arginine vasopressin (AVP) in the presence and absence of 10 microM nonradioactive AVP. Saturable, specific binding to a single site with a Kd of 6.2 nM and Bmax of 111 fmol/mg protein was detected. Vasopressin had no effect on RPE cyclic AMP levels measured by radioimmunoassay. Intracellular calcium fluxes were measured by spectrofluorometry of RPE cell suspensions preloaded with quin 2. The baseline cytosolic calcium level was 217 +/- 20 nM, and AVP caused a concentration-dependent increase in this level with a 3.5-fold maximal response at 10(-6) M and an EC50 of 120 nM. The production of inositol phosphates was measured in RPE preloaded with [3H]myoinositol, and AVP caused a concentration-dependent increase in their production with a 2.1-fold maximal response at 10(-5) M and an EC50 of 80 nM. A specific vasopressin receptor antagonist, SKF 101926, prevented the AVP-induced increase in calcium mobilization and inositol phosphate production in RPE. These data suggest that RPE cells possess V1 AVP receptors coupled to calcium mobilization and inositol phosphate metabolism.

Aminoquinolines↗
PubMed1989

Human retinal pigment epithelial cells in culture possess A2-adenosine receptors.

Adenosine agonists cause a marked stimulation in cyclic AMP accumulation in whole human retinal pigment epithelial (RPE) cells in the presence of adenosine deaminase and papaverine, a phosphodiesterase inhibitor. N-Ethylcarboxamidoadenosine (NECA) stimulates cyclic AMP accumulation 16.1-fold above basal with an EC50 of 2.5 x 10(-7) M. It is also an effective (1.9-fold) stimulator of adenylate cyclase activity in RPE membrane preparations and a modest (1.22-fold) stimulator in the presence of forskolin in RPE cell membranes prepared from freshly isolated porcine RPE. N6-Cyclopentyladenosine (CPA) and N6-phenylisopropyladenosine (PIA) also increase cyclic AMP levels with EC50s of 4.9 x 10(6) M (8.9-fold above basal) and 3.5 x 10(-6) M (8.0-fold above basal) respectively. This potency order (NECA greater than PIA greater than CPA) is typical of A2-adenosine receptors. The relatively A1-selective agonists 10(-7) M indicating that RPE cells do not have A1-receptors which inhibit adenylate cyclase. Three adenosine receptor antagonists, BW-A1433U, 8-cyclopentyltheophylline and 8-sulfophenyltheophylline, blocked the NECA-induced stimulation of cyclic AMP accumulation with IC50s of 0.36 microM, 1.5 microM, and 75 microM respectively. Since alteration of cAMP levels has been demonstrated to affect several RPE functions, including cell migration, resorption of subretinal fluid, and phagocytosis, adenosine may play a significant regulatory role in RPE.

Adenosine↗
PubMed1989

Effects of betaxolol/timolol on epinephrine stimulated cyclic-AMP levels in human trabecular meshwork cells.

The effects of timolol and betaxolol were compared for blocking beta agonist stimulation of cyclic-AMP in cultured human trabecular meshwork cells. Epinephrine (10(-5) M) produced a large and rapid increase in HTM cyclic-AMP; timolol (10(-6) M), at concentrations readily achieved in the aqueous humor after 0.5% eyedrops, completely blocked this effect. Recovery from timolol treatment appeared to be relatively slow, with only a 30-40% recovery observed by 9 hours. In comparison, betaxolol (10(-6) M) produced a smaller blockade of the epinephrine effects; a rapid recovery from the betaxolol effects was observed, with a greater than half-maximal response to epinephrine observed 15 minutes after removal of this beta blocker. These findings may help to explain the clinical observations of an outflow facility effect of epinephrine when used in combination protocols with betaxolol, but not with timolol.

Betaxolol↗
PubMed1988

Human retinal pigment epithelial cells possess muscarinic receptors coupled to calcium mobilization.

Human retinal pigment epithelial (RPE) cells in culture demonstrated saturable specific binding of [3H]quinuclidinyl benzilate (QNB). Specific binding represents about 75% of total binding. Scatchard analysis yields a Kd of 0.178 nM and Bmax of 42 fmol/mg protein. Atropine and carbachol show typical displacement curves, and a Hill plot has a slope of 0.96, suggesting a homogeneous population of receptors. Muscarinic agonists have no effect on intracellular cyclic adenosine monophosphate levels in RPE cells measured by radioimmunoassay, nor do they alter the isoproterenol-induced stimulation of adenylate cyclase. However, both acetylcholine and carbachol cause a rapid increase in intracellular calcium concentration measured by the fluorescent indicator quin 2. Atropine reverses the calcium rise when added after agonist and prevents the rise when added prior to agonist. These data suggest that human RPE cells possess muscarinic receptors coupled to calcium mobilization.

Atropine↗
PubMed1987

Cyclic 3',5'-adenosine monophosphate modulates vascular endothelial cell migration in vitro.

Using a modified Boyden chamber assay, we have examined the effect of cyclic nucleotides on bovine aortic endothelial cell migration in vitro. Dibutyrl cyclic 3',5'-adenosine monophosphate (5 mM) inhibited endothelial cell random migration by 67% and inhibited fibronectin-induced chemotaxis by 75%. Agents which significantly stimulated adenylate cyclase activity in endothelial cell membranes were also effective inhibitors of endothelial cell migration. Timolol blocked both the isoproterenol-induced stimulation of adenylate cyclase and the ability of isoproterenol to inhibit endothelial cell migration. Caffeine and isoproterenol together had a greater inhibitory effect on endothelial cell motility than either alone. These data suggest that cAMP may modulate vascular endothelial cell migration in an inhibitory fashion.

Adenylyl Cyclases↗
PubMed1987

Characterization of adenylate cyclase in human retinal pigment epithelial cells in vitro.

Human retinal pigment epithelial cells in culture demonstrate adenylate cyclase activity. It is membrane-bound and modulated by GTP regulatory proteins. It is effectively activated only by beta-adrenergic agonists (L-isoproterenol greater than or equal to L-epinephrine greater than L-norepinephrine) and some prostaglandins (PGE1 and PGE2, but not PGF1 alpha). The adrenergic response appears to be mediated by beta-2 receptors. No inhibitory ligands could be demonstrated. Its characteristics, which are similar to functional adenylate cyclase complexes in other mammalian cells, and its selective and sensitive agonist responsiveness, suggest a possible physiologic role in the regulation of human retinal pigment epithelial-cell function.

Adenylyl Cyclases↗
PubMed1986

Cyclic 3',5'-adenosine monophosphate modulates retinal pigment epithelial cell migration in vitro.

Retinal pigment epithelial (RPE) cell migration has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR). Using a modified Boyden chamber assay, we have examined the effect of cyclic nucleotides on human RPE cell migration in vitro. Dibutyryl cyclic 3',5'-adenosine monophosphate (cAMP) (10(-3) mmol/L) inhibits RPE cell random migration by 83%, fibronectin-induced chemotaxis by 61%, and platelet-derived growth factor-induced chemotaxis by 68%. Random and directed migration of RPE cells is not significantly affected by 8-bromo cyclic 3',5'-guanosine monophosphate. Agents that significantly increase intracellular levels of cAMP are also inhibitors of RPE cell migration. Though there is a fairly good correlation for most drugs for their ability to stimulate cAMP production and their ability to inhibit cell migration, it is not perfect, suggesting that some drugs may modulate migration by more than one mechanism. Timolol blocked both the isoproterenol-induced stimulation of RPE adenylate cyclase and attenuated the ability of isoproterenol to inhibit RPE migration. These data suggest that cAMP may modulate RPE cell migration in an inhibitory fashion. Elucidation of the biochemical events involved in RPE cell migration could provide information that might be useful in planning a strategy to attempt pharmacologic control of proliferative vitreoretinopathy.

Adenylyl Cyclases↗
PubMed1986

Essential fatty acid consideration at birth in the premature neonate and the specific requirement for preformed prostaglandin precursors in the infant.

The essentiality of certain PUFA is probably related to their capability to be incorporated into lipids and to act as precursor in the formation of ecosanoids. Esterified to phospholipids, the EFA influence the physico-chemical characteristics of biomembranes. Normal growth of infants is dependent upon an adequate supply of EFA. The human fetus, like the adult, is unable to synthesize the EFA, which must therefore be derived from the maternal circulation and pass through the placenta. Increased concentration of the polyenoic fatty acids with advanced gestational age may result from increased synthetic activity of these fatty acids by the fetus or the placenta or by preferential transfer of these fatty acids across the placenta. Several clinical manifestations have been ascribed in the human infant to prolonged EFA deficiency; however, none of these findings were noted in a group of sick newborn infants with very rapid onset of deficiency. Platelet dysfunction, decreased prostaglandin biosynthesis and turnover and altered pulmonary surfactant are among the effects of EFA deficiency on infants. Supplementation of the diet with EFA, parenterally or by the inunction of oil rich in linoleic acid, were reported to alleviate the symptoms of EPA deficiency. The minimal estimated requirement of linoleic acid is 1% of calories and 4% is an optimal intake. Most diets, including human breast milk, infant formulas and parenteral fat emulsions, far exceed the optimal intake of linoleic acid. Relatively little is known about the possible effects of high levels of linoleate in the diet.

Blood Platelets↗
PubMed1986

Prostaglandins in breast milk.

Levels of prostaglandin E2, prostaglandins F2 alpha and prostacyclin (measured as 6-keto PGF1 alpha) were measured by radioimmunoassay in aliquots of foremilk and hindmilk obtained at different stages of lactation, (colostrum, transitional and mature milk), from ten healthy nursing mothers who delivered at term. Immunoreactive prostaglandins E2, F2 alpha and the stable metabolite of prostacyclin 6-keto PGF1 alpha were detected in all fresh human milk samples but not in cow's milk-based formulas. The source of prostaglandins and prostacyclin in breast milk is related to local synthesis of the mammary gland and to the synthesis by the cellular elements of breast milk but not to their level in the maternal circulation.

Animals↗
PubMed1985

Topical acetazolamide and methazolamide delivered by contact lenses.

Topical acetazolamide has been previously found to be ineffective in lowering intraocular pressure (IOP). Using high-water-content soft contact lenses (Sauflon PW) soaked in acetazolamide, we observed a statistically significant ipsilateral decrease in IOP of 6.3 +/- 0.4 mm Hg in the treated eyes of albino rabbits. The duration of the effect was up to 7 1/2 hours. Methazolamide-soaked contact lenses produced a maximum unilateral reduction of similar magnitude but shorter duration. Both serum and aqueous humor analyses for pH, carbon dioxide pressure, bicarbonate, and base excess indicate that acetazolamide delivered by soft contact lenses is able to penetrate the cornea in sufficient concentration to lower IOP by a local mechanism in rabbits without significant systemic absorption.

Acetazolamide↗
PubMed1979

Head growth in sick premature infants--a longitudinal study.

Serial weekly measurements of somatic growth and head circumference were made for ten weeks on 41 appropriately grown sick preterm infants (gestational age 28 to 32 weeks) with severe neonatal problems. Twenty-seven (66%) required prolonged assisted ventilation. During the period of acute illness, the velocity of growth for the sick infants was below that of the normal fetus, with deviation away from and below the normal fetal growth curve. During recovery, head growth paralleled that of normal fetal growth, and subsequently rapid "catch-up" growth in head circumference occurred. By comparison, six similar infants, whose head circumference followed the intrauterine growth curve, proved to have hydrocephalus. These results suggest that: (1) the brain participates in the growth retardation associated with being sick and premature and that apparently normal head growth under comparable circumstances may be associated with hydrocephalus; (2) in spite of an energy intake ranging from 80 to 120 kcal/kg/day by the end of the second postpartum week, normal growth in the sick low-birth-weight infant does not occur until their acute illness has resolved.

Female↗
PubMed1979

Familial infantile scoliosis associated with bilateral paralysis of conjugate gaze.

A family with two sibs suffering from idiopathic infantile scoliosis associated with bilateral paralysis of conjugate gaze is reported. Although the parental consanguinity and the involvement of patients of both sexes in this family are suggestive of an autosomal recessive mode of inheritance, a dominant or multifactorial pattern remains a possibility.

Child, Preschool↗