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Biomedical subjects

A L Ackerman

Publications and source records attributed to A L Ackerman.

13 recordsLinked to original sources
PubMed1997

The effect of point mutations on the free energy of transmembrane alpha-helix dimerization.

Glycophorin A forms homodimers through interaction of the single, helical transmembrane domains of the monomers. The dimers are stable in sodium dodecylsulfate (SDS), permitting a number of studies that have identified a critical motif of residues that mediates dimer formation. We have used analytical ultracentrifugation to measure the energy of dimerization in a non-denaturing detergent solution and have observed the changes in energy arising from two of the mutants previously studied. Use of the detergent pentaoxyethylene octyl ether (C8E5) is a great advantage, since its micelles are neutrally buoyant and the detergent allows a reversible association to occur between monomer and dimer states of the glycophorin A transmembrane helices during the time-scale of sedimentation equilibrium. Use of this detergent in analytical ultracentrifugation may enable a wide range of studies of molecular association events in membrane proteins. We find that the glycophorin A transmembrane helix dimerizes with a dissociation constant of 240(+/-50) nM, corresponding to a free energy of dissociation of 9.0(+/-0.1) kcal mol-1. Point mutants that were found to be disruptive in SDS (L75A, I76A) reduced the dimer affinity in the C8E5 detergent environment (Kd=1.7(+/-0.2) microM and 4.2(+/-0.9) microM, respectively). Thus, the earlier findings are placed on a quantitative, relative energy scale of association by our measurements. Molecular modeling and simulations suggest that the energy differences can be accounted for as changes in van der Waals interactions between helices.

Cell Membrane↗
PubMed1989

Cryotherapy for stage 3+ retinopathy of prematurity: visual and anatomic results.

Fifty eyes of 25 preterm infants with stage 3+ retinopathy of prematurity (ROP) and 180 degrees to 360 degrees of preretinal neovascularization were treated with cryotherapy to ablate the peripheral zone of avascular retina. All neovascularization regressed. Eleven eyes developed traction detachments, eight of which were successfully reattached with scleral buckling surgery. With follow-up of 6 to 70 months (mean, 29 months), visual acuity was 20/30 to 20/60 in 11 of 16 eyes (69%) of eight children old enough to be tested, and 20/100 to 20/200 in three of these eyes. Thus, vision was 20/200 or better in 14 of 16 eyes (87.5%). Visual behavior was normal for their age in 16 infants too young to test. One child developed bilateral inoperable detachments. We conclude that cryotherapy safely resolves stage 3+ ROP with excellent visual results.

Cryosurgery↗
PubMed1988

Successful treatment of advanced retinopathy of prematurity.

Thirty-nine eyes of 20 premature infants, mean birthweight 922 g, mean gestational age 27 weeks, with active retinopathy of prematurity (ROP), were treated. Thirty-one eyes with stage 3+ ROP and 180 degrees to 360 degrees of preretinal neovascularization received cryotherapy to ablate the zone of peripheral avascular retina. All underwent complete regression of active disease. Eight of these eyes subsequently developed retinal detachments due to ongoing vitreous traction. One detachment was inoperable. Six eyes were successfully reattached following scleral buckling surgery. One of these six redetached and became inoperable after 20 months. Pars plicata vitrectomy was not successful in reattaching the eighth case. Twenty-eight of these 31 eyes retain useful visual acuity with follow-up of 15 to 70 months (mean 41 months). There have been no complications resulting from cryotherapy. Eight other eyes with stage 4 ROP (traction retinal detachment) were treated with cryotherapy and scleral buckling surgery. All were initially reattached, but ongoing vitreoretinal traction caused redetachment in five. One was inoperable. "Open sky" vitrectomy was successful in reattaching three of the other four. Of the six cases that remained reattached with follow-up of 6 to 51 months, only two retain useful vision.

Cryosurgery↗
PubMed1985

A reduced incidence of cystoid macular edema following retinal detachment surgery using diathermy.

Cystoid macular edema (CME) is recognized as an important cause of decreased visual acuity following successful retinal detachment surgery. Postoperative fluorescein angiographic studies suggest an incidence of up to 28% in phakic patients, and 50% in aphakic cases. Cryotherapy was used with scleral buckling in all these previous studies. In the series reported here, diathermy with scleral buckling was used to reattach the retina. In 126 phakic eyes the incidence of CME was 5.6% (7 cases). This is the lowest incidence reported in any series. We attribute these results to reduced intraocular inflammation using diathermy as compared to cryotherapy.

Aged↗
PubMed1985

The treatment of advanced retinopathy of prematurity by cryotherapy and scleral buckling surgery.

Seventeen eyes of nine extremely premature infants with severe acute proliferative retinopathy of prematurity (ROP, Grades III-V) were treated. Cryotherapy alone was used in ten eyes to ablate extensive areas of avascular retina to thereby induce involution of widespread intravitreous neovascularization. No attempt was made to directly treat the arteriovenous shunt or neovascularization itself. Scleral buckling surgery was used in combination with cryotherapy in seven additional eyes to relieve diffuse vitreous traction to intravitreous neovascularization which had caused extensive traction retinal detachment. Cryotherapy was uniformly successful in causing involution of widespread intravitreous neovascularization in all patients treated. Scleral buckling surgery was initially effective in reattaching the retina in all cases but late manifestations of severe ongoing vitreoretinal traction required additional open-sky vitrectomy in two eyes and resulted in inoperable recurrent total traction retinal detachment in one eye and extensive macular scarring in another. A comparison is made between the proliferative retinopathies seen in ROP and diabetes mellitus and a rationale for effective cryotherapy in ROP is presented. In our clinical experience, the single most important prognostic factor determining the potential severity of ROP is the width and extent of the retinal avascular zone. The wider the zone, the greater the probability of rapid progression from early to advanced grades of disease.

Cryosurgery↗
PubMed1983

Massive exudative retinal and choroidal detachments following scleral buckling surgery.

Three aphakic male patients underwent successful scleral buckling surgery for unilateral rhegmatogenous retinal detachment. Within a two-week postoperative period, each developed severe ocular pain with massive exudative retinal and choroidal detachments resembling recurrent rhegmatogenous or traction retinal detachment or implant infection. Systemic prednisone therapy resulted in prompt resolution of ocular pain and reabsorption of subretinal and suprachoroidal fluid. It is important to recognize this uncommon postoperative syndrome so that proper medical therapy may be initiated and unnecessary additional retinal or vitreous surgery can be avoided.

Aged↗