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Biomedical subjects

G J Jaffe

Publications and source records attributed to G J Jaffe.

At least 91 records · Page 5Linked to original sources
PubMed1991

Expression of interleukin-1 and interleukin-1 receptor antagonists in endometrial cancer.

The cytokine interleukin-1 (IL-1) can inhibit growth of breast cancer cells in culture and promote cellular differentiation in synergism with other growth factors. A secreted IL-1 receptor antagonist (sIL-1ra) has been described and an intracellular version (icIL-1ra) has been cloned; both antagonists block IL-1-dependent responses. We compared mRNA expression of IL-1 and both receptor antagonists in normal and neoplastic endometrium. RNA was extracted from five benign endometrial and five endometrial cancer whole-tissue specimens, reverse transcribed into cDNA, then amplified by polymerase chain reaction using specific primers for IL-1 alpha, IL-1 beta, sIL-1ra, and icIL-1ra. IL-1 alpha and IL-1 beta were expressed in variable amounts in all tissues; there was no difference in expression between normal and cancer specimens. In contrast, high levels of icIL-1ra were expressed in four of five cancer specimens compared with none of five normal tissues (P = 0.02). There was no expression of sIL-1ra in cancer and normal tissues. These preliminary experiments suggest that IL-1 is ubiquitously expressed in endometrial tissues whereas endometrial cancer preferentially expresses icIL-1ra. IcIL-1ra may regulate IL-1-mediated events such as growth and differentiation in endometrial neoplasia.

Female↗
PubMed1991

Retinal pigment epithelial cells of the posterior pole have fewer Na/K adenosine triphosphatase pumps than peripheral cells.

The density of Na/K adenosine triphosphatase (ATPase) pumps in retinal pigment epithelial (RPE) cells in different retinal regions was quantified by measuring the binding of 3H-ouabain to RPE in cow and human eyecups. In bovine eyes, pump density was estimated in RPE samples isolated from three retinal regions outlined with a 7-mm trephine: one from the posterior pole in the area centralis and two from the superior, equatorial retina representing unpigmented (in the tapetum) and pigmented zones. In human eyes, RPE samples were isolated from a posterior region centered around the macula and one superior region. Ouabain binding to RPE of the posterior pole of both species was approximately 40-60% lower than binding to RPE of more peripheral regions in the same eyes. For bovine eyes, ouabain binding did not differ between pigmented and unpigmented cells of the superior retina, suggesting that reduced binding in the relatively amelanotic posterior cells was not related to levels of pigmentation. For human RPE, binding to posterior cells was lower in eyes from donors of all ages (range, 17-90 yr). The data suggest that Na/K ATPase pump site density is lower in posterior RPE cells of both bovine and human eyes, perhaps due to a regional difference in requirements for ionic regulation.

Adolescent↗
PubMed1990

Risk factors for postvitrectomy fibrin formation.

We prospectively studied 194 patients undergoing vitrectomy between July 1988 and April 1989 to determine the incidence of postvitrectomy intraocular fibrin formation and the association of a variety of preoperative and intraoperative variables with the formation of severe postvitrectomy fibrin. Overall, 62 (32%) patients developed postvitrectomy fibrin; 25 (13%) had mild fibrin formation, 13 (6.5%) had moderate fibrin formation, and 24 (12.4%) had severe fibrin formation. By logistic multivariate analysis, preoperative factors that were independently predictive of severe fibrin formation included severe flare (P = .004), the presence of a previously placed scleral buckle (P = .001), and poor preoperative visual acuity (P = .007). Anterior epiretinal membrane dissection was the only intraoperative factor that was independently associated with an increased fibrin risk (P = .0003). A risk score derived from the multivariate analysis effectively categorized patients according to their likelihood of developing severe postvitrectomy fibrin. Results of this study may be useful in designing prophylactic interventions to decrease postvitrectomy fibrin formation.

Adult↗
PubMed1990

Combined phacoemulsification and pars plana vitrectomy.

Combined phacoemulsification and pars plana vitrectomy were performed in eight eyes with cataract and vitreoretinal disease. Six eyes had tractional retinal detachment and/or nonclearing vitreous hemorrhage, one eye had a retained metallic intraocular foreign body, and one eye had a traumatic retinal detachment. In six eyes, a posterior chamber lens implant was placed in the capsular bag. Postoperative visual acuity improved in each case and ranged between 20/15 and 6/200. There were no perioperative complications, and the posterior chamber lens implant appeared well tolerated during an average follow-up interval of 8 months (range, 3 to 30 months). This technique allows endocapsular fixation of a posterior chamber lens and provides rapid visual rehabilitation with a single operation.

Adult↗
PubMed1990

Antitransferrin receptor immunotoxin inhibits proliferating human retinal pigment epithelial cells.

Cultured human retinal pigment epithelial cells were exposed to an immunotoxin composed of a monoclonal antibody, 454A12, directed against transferrin receptors conjugated to a toxin, recombinant ricin A chain. Exposure of proliferating human retinal pigment epithelial cells to the immunotoxin (0.1 to 10,000 ng/mL) caused a statistically significant (P less than .0001) decrease in the number of cells. This inhibitory effect was induced after an exposure to the immunotoxin as short as 5 minutes and was maximal after 24 hours of exposure. The diminution in cell number was dose dependent over the range from 0.1 to 100 ng/mL. Monoclonal antibody alone, recombinant ricin A chain alone, or an irrelevant immunotoxin, MOP21C monoclonal antibody-recombinant ricin A, did not diminish the number of cells. There was a marked decrease in DNA synthesis measured by nuclear tritiated thymidine incorporation that accompanied the immunotoxin-mediated decrease in cell number. Viable cells remaining after exposure to the immunotoxin (0.1 to 10,000 ng/mL) were morphologically abnormal; typically the cells had elongated spindle-shaped processes and had lost their normal cuboidal appearance. In contrast, cell number was not decreased in confluent human retinal pigment epithelial cells after treatment with maximal doses of immunotoxin. Morphologic changes similar to those seen in proliferating cells were observed in confluent cells exposed to more than 100 ng/mL of immunotoxin. The effect of the immunotoxin was species specific because large doses of immunotoxin did not reduce the number of viable cells in proliferating or confluent pig retinal pigment epithelial cells or cause observable morphologic changes in this cell type. Our results indicate that the immunotoxin selectively inhibited proliferating retinal pigment epithelial cells by receptor-mediated internalization of the antitransferrin receptor monoclonal antibody-recombinant ricin A chain conjugate.

Cell Count↗
PubMed1990

Tissue plasminogen activator for postvitrectomy fibrin formation.

The authors injected 25 micrograms of recombinant tissue plasminogen activator (tPA) into the anterior chamber or vitreous cavity of 23 eyes of 22 patients with severe intraocular fibrin formation that developed after vitrectomy surgery for complicated cases of proliferative vitreoretinopathy (PVR) (13 eyes), diabetic traction retinal detachment (TRD) (7 eyes), or endophthalmitis (3 eyes). Tissue plasminogen activator injected an average (+/- standard deviation) of 73 +/- 63 hours after vitrectomy surgery resulted in complete fibrinolysis in 21 of 23 eyes and partial fibrinolysis in one eye. The mean time to fibrin resolution was 3.0 +/- 1.0 hours. Four eyes required repeat tPA injection for recurrent fibrin formation; repeat injection resulted in complete fibrinolysis in each case. The mean follow-up duration after tPA administration was 6 months. At the final follow-up examination, the retina was totally attached in 18 of 23 eyes and was partially attached in 2. Visual acuity improved in 12 eyes (52%); it was at least 20/400 in 8. Complications of tPA injection included hyphema (2 patients) and corneal stromal thickening (2 patients). Mild, transient, periocular pain that was easily managed with non-narcotic analgesia developed in three patients.

Adolescent↗
PubMed1990

Magnetic resonance imaging of juxtapapillary plaques in cadaver eyes.

Adequate treatment of juxtapapillary melanomas with episcleral plaque brachytherapy using lower energy radiation sources may be difficult because of uncertainties regarding the relationship of the plaque to the optic nerve and tumour base. We obtained magnetic resonance images of a dummy plaque placed in a juxtapapillary location in cadaver specimens. Although it is possible to place a plaque in close association with the optic nerve sheath, a tissue barrier exists which may prevent actual contact between the plaque and nerve. Posterior tilting of the plaque may also occur. Because of these uncertainties regarding plaque placement, juxtapapillary melanomas should be considered a distinct subgroup when evaluating the efficacy of radioactive plaque brachytherapy in the treatment of choroidal melanoma.

Brachytherapy↗
PubMed1989

Treatment of postvitrectomy fibrin pupillary block with tissue plasminogen activator.

We injected 25 micrograms of recombinant tissue plasminogen activator into the anterior chamber or the vitreous cavity in seven aphakic patients for pupillary block caused by a complete fibrin pupillary membrane that formed after vitrectomy with fluid-gas exchange. Progressive fibrin deposition resulted in pupillary block by three days after vitrectomy surgery in six patients, and seven days after vitrectomy in one patient. The pupillary block was associated with increased intraocular pressure in six patients. Tissue plasminogen activator was injected via the corneoscleral limbus in five patients and via the pars plana in two patients. In all patients, injection of tissue plasminogen activator resulted in complete fibrinolysis of the fibrin pupillary membrane within four hours, associated with a deepening of the anterior chamber. In the six patients with increased intraocular pressure at the time of tissue plasminogen activator injection, dissolution of the fibrin membrane was associated with a decrease in pressure. In all patients, intraocular pressure had returned to normal by three days after the injection. No complications were associated with the injection.

Adult↗
PubMed1989

Photoablation of ocular melanoma with a high-powered argon endolaser.

We studied the use of a 15-W argon blue-green laser in the treatment of choroidal melanoma in a rabbit model. Greene melanoma cells were used to produce 2- to 4-mm thick tumors posteriorly in the suprachoroidal space in pigmented rabbits. Endophotocoagulation delivered through a 600-micron fiberoptic probe was performed to ablate the tumor tissue and a surrounding margin of normal tissue. A vitreous cutter was used simultaneously to remove liberated necrotic debris. The effect of the laser on tumor and normal ocular tissue was evaluated by light microscopy and the extent of the proliferative response by tritiated thymidine radioautography. Application of 100 to 400 pulses of laser energy using treatment parameters of 12 to 14 W of power and 0.1-s pulses resulted in complete ablation of melanoma tissue, overlying retina, and choroid. There was no substantial intraoperative or postoperative hemorrhage. Material liberated during the laser treatment was found to be nonviable. The effect of the laser on tissue appeared localized to within approximately 1.25 mm of the margin of the central lesion. The high-energy argon laser seems to offer a means of effectively ablating melanoma tissue via an internal resection approach.

Animals↗
PubMed1989

Ab interno sclerostomy with a high-powered argon endolaser. Clinicopathologic correlation.

A high-powered argon blue-green laser coupled to a 300-microns quartz fiberoptic probe was used to create an ab interno sclerostomy in a patient undergoing enucleation for a blind painful eye. Despite the presence of diffuse rubeosis, 360 degrees peripheral anterior synechiae, and superior conjunctival scarring, it was possible to create a full-thickness defect from the anterior chamber angle to the subconjunctival space without operative complications. Six laser applications were required using 8 W of power per pulse and 0.1-second pulse duration. The eye was enucleated immediately after the laser procedure, prepared for light microscopy, and sectioned serially. Histologic analysis demonstrated a patent fistula approximately 300 microns in diameter with sharp wound margins. Tissue damage was localized to within 150 microns of the sclerostomy. The overlying conjunctiva was intact.

Adult↗
PubMed1989

Ferromagnetic hyperthermia and iodine 125 brachytherapy in the treatment of choroidal melanoma in a rabbit model.

Hyperthermia has been combined with conventional radiation methods to achieve enhanced tumor destruction. We combined iodine 125 seeds with ferromagnetic thermoseeds in a single plaque to simultaneously deliver radiation and heat in a rabbit model of choroidal melanoma. Initially, six ferromagnetic thermoseeds were placed in parallel on a 14-mm episcleral plaque. The plaques were placed on normal rabbit eyes and on eyes containing transvitreally implanted choroidal melanoma. The heating response was assessed in both normal and tumor-containing eyes. Rigid copper-constantan and flexible Baily thermocouples were used to monitor temperature responses. The animals were subjected to an electromagnetic field of 100 kHz, with power of 1100 to 1500 W. The thermoseeds autoregulated at 48.2 degrees C. Scleral temperatures stabilized at 45.8 degrees C +/- 0.4 degrees C (SD), while temperatures at the base of the tumor stabilized at 43.6 degrees C +/- 0.1 degrees C. Ferromagnetic thermoseeds were then combined with iodine 125 seeds. Similar temperature responses were recorded, and autoradiographic findings confirmed a uniform radiation distribution. Varying the amount or type of ferromagnetic material in the thermoseeds allows the delivery of heat at virtually any temperature. Ferromagnetic hyperthermia may provide a more simplified approach over currently available methods of heat delivery.

Animals↗
PubMed1989

Ouabain-sensitive Na+-K+ ATPase pumps in cultured human retinal pigment epithelium.

The expression of Na+-K+ ATPase pumps was studied in cultured human retinal pigment epithelium (RPE). Pump site number was measured by quantitation of the specific binding of [3H]ouabain to cultures of varying density. Specific binding of [3H]ouabain was time- and concentration-dependent, and was inhibited by potassium and by excess unlabeled ouabain. Estimates of pump site number based upon specific [3H]ouabain binding indicated that the number of pumps per RPE cell was maximal in sparse cultures and declined six-fold as cultures became confluent. Pump activity, determined by measurement of specific 86Rb (rubidium) uptake, was also greater in sparse than in dense cultures. Quantitation of [3H]thymidine incorporation as a measure of cell proliferation demonstrated that proliferation in RPE cultures decreased logarithmically as culture density increased. Increased pump site number in cultured RPE, therefore, correlated with increased cell proliferation and decreased culture density. We conclude that human RPE express ouabain-sensitive Na+-K+ ATPase in vitro and maximal expression is observed in sparse, proliferating cultures.

Biological Transport, Active↗
PubMed1988

Ab interno sclerostomy with a high-powered argon endolaser.

We used a high-energy argon blue-green laser (15-W maximum power output) to create full-thickness sclerostomies from the region of the anterior chamber angle to the subconjunctival space in pigmented rabbits using an ab interno approach. One to four laser pulses delivered through a 300-micron noncontact fiberoptic probe produced patent sclerostomies in all 20 eyes treated using 0.1-second pulse duration and 5 to 14 W of power. No intraoperative complications were encountered. Intraocular pressure, measured in 12 animals, decreased an average of 12 mm Hg in the treated eye relative to the fellow eye on the first postoperative day. The drop in intraocular pressure was associated with formation of a functioning filtration bleb. Intraocular pressure returned to preoperative levels in ten of 12 (83%) of the animals by the fourth postoperative day, and there was an associated flattening of the filtration bleb. Histologic and radioautographic analysis indicated that the effect of the laser was focal. Tissue damage and cellular proliferative response were limited to within approximately 200 micron of the wound margin.

Animals↗
PubMed1988

Progression of nonproliferative diabetic retinopathy following cataract extraction.

Eight patients experienced progression of nonproliferative diabetic retinopathy following cataract extraction. Six patients underwent an uncomplicated extracapsular cataract extraction with placement of a posterior chamber intraocular lens, and in two patients, surgery was complicated by vitreous loss. In each case the retinopathy progressed to a severe exudative form of diabetic macular edema, characterized by diffuse retinal thickening and fluorescein leakage with increased dot and blot hemorrhages and lipid deposition. In all patients, clinically significant macular edema developed in the eye that had been operated on, and six patients received laser photocoagulation for this condition. Final visual acuity was worse than preoperative visual acuity in six of eight patients, and it was unchanged in two of six patients. No patient achieved a visual acuity better than 20/50. The fellow eyes, which were not operated on, remained stable during the follow-up period.

Aged↗