Targeted overexpression of phospholamban to mouse atrium depresses Ca2+ transport and contractility.

Phospholamban is a small phosphoprotein regulator of the Ca2+-pump of cardiac sarcoplasmic reticulum. Dephosphorylated phospholamban inhibits the Ca2+-pump and depresses contractility, whereas phosphorylation of phospholamban by cAMP-activated mechanisms relieves this inhibition and increases contractility. In order to better understand the function of phospholamban in living systems, a transgenic mouse model was established employing targeted overexpression of phospholamban to the atrium, which normally expresses low levels of the protein. Overexpression was achieved by fusing the alpha-MHC-promoter or the ANF-promoter to the phospholamban gene. Double transgenic mice were created by mating mice positive for each transgene. In single transgenic lineages, phospholamban was overexpressed four to six-fold in left atrium. In the double transgenic mice, phospholamban was overexpressed eight- to nine-fold. In the three transgenic strains. Ca2+ uptake by the sarcoplasmic reticulum was depressed to 22-30% of control values at low ionized calcium. This depression of Ca2+ uptake was largely reversed by addition of a phospholamban monoclonal antibody. In the atrial muscle strips, the time course of contraction was increased in a concentration-dependent manner by overexpression of phospholamban, whereas the basal developed tension was decreased up to 85% by phospholamban-overexpression. In all transgenic lineages, isoproterenol, a beta-adrenoceptor agonist, reversed the depression of contractility caused by overexpression of phospholamban and significantly shortened time parameters to levels approaching control values. These data demonstrate that overexpression of phospholamban in a mammalian myocardial tissue normally deficient in the protein substantially inhibits basal contractility, and furthermore suggest that in myocardial tissues containing high levels of the protein, phosphorylation of phospholamban can account for many of the positive inotropic and lusitropic effects of beta-adrenergic stimulation.

Retinal detachment following cataract surgery with capsulorhexis.

PURPOSE: To estimate the incidence of retinal detachment after cataract surgery with capsulorhexis. METHODS: A consecutive series of 2,150 cataract operations were followed for incidence of retinal detachment. A series of 1,000 patients from this group were analyzed for high risk factors: myopia, age, sex, operative complications and capsulotomy. RESULTS: With minimum one year follow up in 90% of patients the incidence of retinal detachment was 0.25% (5 cases). CONCLUSION: The true incidence of retinal detachment after cataract surgery remains elusive. There is probably a trend toward lower incidence compared to previous reports.

Purification of a 90-kDa protein (Band VII) from cardiac sarcoplasmic reticulum. Identification as calnexin and localization of casein kinase II phosphorylation sites.

Purification and sequencing of proteins from cardiac sarcoplasmic reticulum (SR) vesicles have provided a framework for the study of SR function. Included among the SR proteins so far investigated are a collection of intralumenal proteins that stain blue with the protein dye Stains-All in sodium dodecyl sulfate-polyacrylamide gels. A single prominent blue staining SR protein of apparent M(r) = 90,000 (Band VII), however, has remained uncharacterized. In the work described here, purification of Band VII from dog cardiac SR vesicles, along with amino acid sequencing and cDNA cloning, identified this protein as calnexin, a homologue of calreticulin recently described in dog pancreatic microsomes. Using ryanodine-mediated calcium oxalate loading of SR vesicles followed by density gradient centrifugation, we have shown that calnexin is a bona fide SR protein and an integral constituent of both junctional and free SR vesicles. Calnexin was found to be a substrate for casein kinase II and was phosphorylated at two distinct sites localized to the carboxyl- and amino-terminal ends of the molecule. Enrichment of calnexin in cardiac SR vesicles indicates a role for calnexin involving the specialized function of the SR membrane.

Increased intraocular pressure in the immediate postoperative period after extracapsular cataract extraction.

We evaluated the immediate intraocular pressure increase after extracapsular cataract surgery in 58 eyes. Two to three hours postoperatively, 34 eyes (59%) developed an intraocular pressure greater than or equal to 25 mm Hg. We found an intraocular pressure of at least 40 mm Hg in seven eyes. Mean intraocular pressure two to three hours postoperatively was 8.9 +/- 9.8 mm Hg greater than the preoperative intraocular pressure. The use of intraocular sodium hyaluronate had no apparent effect on intraocular pressure.

Early complications following Q-switched neodymium: YAG laser posterior capsulotomy.

A prospective evaluation was conducted of Q-switched neodymium: YAG laser capsulotomy in 53 eyes followed for one postoperative month. The first 31 eyes were seen at two-hour intervals for the first eight hours, and the remaining eyes were checked only at the second postoperative hour during that day. Eighty-nine percent of eyes required a pulse setting of less than 1.7 mJ to successfully penetrate the posterior capsule. Visual acuity was improved in 91% of eyes. A transient immediate postoperative intraocular pressure (IOP) elevation was seen in over 75% of treated eyes, and one-third had an IOP elevation greater than 10 mmHg over the preoperative IOP. This elevation was most common in glaucomatous eyes and occurred in almost one-half of the treated eyes by the second postoperative hour. This IOP change did not correlate with the degree of inflammation, bleeding, anterior chamber debris, or total energy delivered. Minimal iris bleeding occurred in 9% of treated eyes and was associated with iridocapsular adhesions. Eighty-one percent of eyes with posterior chamber implants developed some degree of lens damage.

Funduscopically controlled scotometry.

The following is a brief summary of the results in our ten groups of cases. The positive features of laser scotometry are emphasized. The normal response is well defined: there are no uncertain blind spot margins. The peripheral field is probably extended beyond 60 degrees nasally and superiorly. The size and shape of the small central scotomas associated with macular holes are easily defined and correlated directly with the visible edge of the hole. This result is distinct from the intact subjective response with cystoid maculopathy and surface wrinkling retinopathy. Plotting the margins of peripheral abnormalities such as retinal detachments, retinoschisis, and lattice degeneration is easily done. Schisis is distinguished by an absolute scotoma. This scotometry is facilitated by a larger "normal" field with the laser instrument. Lattice degeneration causes a field defect. A branch retinal artery occlusion shows a slightly jagged border, difficult to detect by standard methods. A cotton-wool spot does not show a total nerve-fiber-bundle defect. Small absolute scotomas are correlated with degenerative changes within nevi. Degenerative changes over small melanomas--ie, the orange spots--also produce absolute field defects. "Bear track" lesions have a normal field, whereas dense black isolated lesions are associated with absolute scotomas. In macular degeneration the bright laser test object is usually visible to the patient within detachments of neuroepithelium, detachments of the pigment epithelium, and over recent subretinal neovascularization. Response is absent over sharply-defined zones of pigment atrophy and over late subretinal fibrovascular mounds. In contrast to the degenerative cases, a selection of hereditary cases showed no direct correlation between the zone of pigment atrophy and the zone of absolute scotoma. The scotoma was much larger than the atrophic region, extending to the edge of the cream-colored subretinal spots. The laser target method sharply defines the absolute scotoma associated with papilledema. It also detects a slit-like nerve-fiber-bundle defect, suggesting progressive damage. Small, but possibly not the earliest, scotomas associated with glaucoma can be detected with laser scotometry. In some cases they are detected when the Goldmann perimetric field is normal. Late residual visual fields are easily defined, since fixation can be directly monitored. The vertical border of hemianopic defects can be defined within one degree of accuracy.

Argon laser photocoagulation treatment of iris cysts following penetrating keratoplasty.

Two patients with iris cysts were successfully treated with argon laser photocoagulation. There was no evidence of recurrence of the cysts 51/2 and four years after treatment. To our knowledge, these cases represent the first reported cases of iris cysts following keratoplasty treated with argon laser photocoagulation that have documented long-term follow-up.

Sarcoidosis with neovascularization of the optic nerve head.

A 25-year-old man with systemic sarcoidosis had neovascularization of the optic nerve heads and associated bilateral vitreous hemorrhages. Oral administration of prednisone produced a prompt resolution of these unusual neovascular fronds and cleared the vitreous hemorrhages.

Retinal fluorograms using oral fluorescein.

Sodium fluorescein may be safely administered orally. The resulting angiograms serve to document the presence or absence of dye leakage in the same manner as venous injection. The oral route of administration is of particular benefit for use in children, patients with inaccessible veins, and patients participating in studies of late retinal vascular leakage, such as postoperative cystoid macular edema. Serum concentrations of the dye plateau between thirty minutes and one hour, at levels approximating those obtained by intravenous injection.

Siphon suction for vitrectomy.

An intravenous container placed below the level of the surgical field can provide a gentle, safe level of suction (+/- 76 mm Hg). This is particularly useful in performing a delicate open-sky anterior vitrectomy.

Retinal fluorography using oral fluorescein.

Fluorescein sodium can be administered safely by mouth. The resulting fluorograms are useful in demonstrating many retinal conditions characterized by bright late leakage, such as cystoid macular edema. Oral administration of fluorescein may be preferred in studies of children, patients with difficult veins, and in some surveys of large patient populations.

Rhegmatogenous retinal detachment with retinal telangiectasia.

A 34-year-old man with unilateral retinal telangiectasia developed a bullous retinal detachment. A horseshoe retinal tear was found at 12 o'clock. The detachment resolved with placement of an encircling scleral buckle. The prompt and permanent resolution of subretinal fluid supported our belief that this was a rhegmatogenous retinal detachment.

Acute ocular leukemia.

A 71-year-old woman had a history of recent weight loss and bilateral decreased visual acuity, bilateral serous detachment, and mental depression. Fluorescein angiograms showed a myriad of retinal pigment epithelial leakage points. Despite extensive evaluation, the cause of her weight loss and ocular process remained uncertain until her death, when postmortem examination revealed leukemia infiltrates of many organs, including the choroid. After death, we correlated the clinical signs and fluorescein angiograms with the histopathologic findings. This case shows that choroidal disease may be a symptom of undetected leukemia.

Laser scotometry in drusen and pits of the optic nerve head.

Laser scotometry is an accurate means of detecting dense blind spots. A small low-energy spot is guided across the fundus from nonseeing to seeing areas. Patient responses are recorded on fundus photographys, allowing direct correlation with fundus pathology. Accuracy to less than 1 degree is feasible. All typical optic nerve drusen tested with this technique had field defects. In cases of optic nerve pits, dense scotomas correlated with the shape of visible nerve fiber defects rather than with the shape of serous retinal detachments.

Peripheral retinal neovascularization in rheumatic fever.

During a two-year period, a 15-year-old boy had three major manifestations of rheumatic fever, ie, chorea, rash, and carditis. Following the acute carditis, peripheral retinal neovascularization appeared in the left eye. Associated transient hemiparesis suggests that emboli may account for the retinal vascular occlusion. Rheumatic fever should be considered in the medical survey of patients who have retinal new vessels of obscure origin.

Use of the argon aiming beam in visual function testing.

The aiming beam of the argon laser photocoagulator can be a useful tool in visual function testing. Applied with the slit lamp delivery system and fundus contact lens, it clearly documents the size of the blind spot surrounding the optic nerve head and the normal area of nonfunctional retina in the periphery. The size of pathologic field defects can be recorded on fundus photographs or retinal drawings by an observer. Safety precautions must be taken to protect all patients from excessive laser energy.

Correlation of clinicopathologic findings in a patient. Congenital night blindness, branch retinal vein occlusion, cilioretinal artery, drusen of the optic nerve head, and intraretinal pigmented lesion.

The ocular clinicopathologic features of this unique patient were congenital stationary night blindness, drusen of the optic nerve head, cilioretinal artery, intraretinal pigmented lesion, and branch retinal vein occlusion. Photocoagulation therapy led to total disappearance of the neovascular tissue, clinically and histopathologically. Histopathologic examination showed an occluded branch vein associated with a sclerotic retinal arteriole. Peripheral to the site of venous occlusion, inner ischemic retinal atrophy was present. The normal complement of rod and cone photoreceptors supports the view that the night blindness in this case was an abnormality in the neural transmission and not on a morphological basis. The pigmented intraretinal lesion proved to be a localized area of retinal and choroidal neovascularization with anastomosis and secondary retinal pigment epithelial hyperplasia. This lesion was identical to Fuchs' dot of myopia but out patient was hyperopic.

Whiplash maculopathy.

Maculopathy in three patients, caused by whiphash injury demonstrated three features that are characteristic of this subtle disturbance of the macula: a history of flexion-extension, head and neck trauma; a history of immediate mild reduction of central visual acuity in one or both eyes; and grayish swelling of the foveal zone accompanied by a small (50 to 100-mu) pit or depression in the fovea. In patients with this disturbance, the retinal opacification and the visual disturbance are transient, but the tiny depression in the retina with its whitish border is permanent.