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Biomedical subjects

E Okun

Publications and source records attributed to E Okun.

12 recordsLinked to original sources

Modulation of histamine type II receptors on CD8+ T cells by interleukin-2 and cimetidine.

CD8+ T cells are known to play a major role in regulating immune functions under normal and disease conditions. In this study a radioligand binding assay was used to quantitate histamine type II (H2) receptors on activated T cells. The objective was to examine the expression of H2 receptors on T cells during activation with interleukin-2 (IL-2) and treatment with cimetidine. Activated suppressor T cells induced by concanavalin A+IL-2 showed a significant (p less than 0.01) increase in H2 receptors compared to the control nonactivated T cells. The T cells expressing the H2 receptors were identified as CD8+ cells; those among them that had an enhanced level of H2 receptors were identified as CD25+. Treatment of activated suppressor cells with the H2 receptor antagonist cimetidine at a concentration of 10(-5) M significantly reduced the number of H2 receptors. Suppressor cells induced by Con A+IL-2 were able to suppress both IgG and IgM production that was reversible with cimetidine. Incubation of lymphocytes with 50 U/ml IL-2 alone in 3-day culture significantly (p less than 0.005) enhanced H2 receptor expression. These studies demonstrate that activated suppressor T cells that are CD8+CD25+ have enhanced levels of H2 receptors and can be modulated by cimetidine.

Antibody Formation

Interleukin 4 alone and with gamma-interferon or alpha-tumor necrosis factor inhibits cell growth and modulates cell surface antigens on human renal cell carcinomas.

Immune cytokines have been shown to play important roles in regulating immune cell functions as well as neoplastic cells. Interleukin-4 (IL4), primarily known as a B-cell growth factor, can also activate and differentiate other immune cells. This cytokine has recently been shown to have immunotherapeutic benefit in tumor-bearing hosts. The present study assessed the effect on human renal cell carcinoma cell lines of recombinant IL4 alone and in combination with recombinant gamma-interferon (IFN) or recombinant alpha-tumor necrosis factor (TNF). IL4 inhibited cell growth of all lines at 250-500 units/ml in a differential manner. Expression of IL4 receptors was demonstrated on renal cell carcinomas. Overall, IFN (500 units/ml) alone inhibited cell growth; however, TNF (500 units/ml) was not as strong an inhibitor. When IL4 was combined with IFN or TNF there was a significant augmentation of cell growth inhibition and modulation of cell morphology of the cell lines. Tumor-associated ganglioside antigens (NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer, NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer, GalNAc beta 1-4 (NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer, and GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer) HLA class I, HLA-DR, and beta 2-microglobulin on the cell surface of renal cancer lines were assessed by flow cytometry and radiometric binding assay. IL4 alone or in combination with other cytokines modulated HLA class I and HLA-DR expression. IL4 and IFN consistently enhanced NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer and GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer expression on individual cell lines. The study demonstrated that IL4 alone or in combination with other cytokines can significantly inhibit growth, and modulate the expression of surface major histocompatibility and tumor-associated antigens of renal cell carcinomas.

Carcinoma, Renal Cell

Modulation of human melanoma cells by interleukin-4 and in combination with gamma-interferon or alpha-tumor necrosis factor.

Immune cytokines have been shown to play important roles in regulating immune cell functions. Interleukin-4 (IL4), originally described as a B-cell growth factor, is known to activate and differentiate other immune cells. IL4 has been given as an immunotherapeutic to tumor-bearing hosts. In this report, we set out to determine whether IL4 can directly modulate growth and expression of surface antigens on human melanoma cells. The effect of recombinant IL4 alone and in combination with recombinant gamma-interferon (IFN) or recombinant alpha-tumor necrosis factor (TNF) on melanoma cell lines was examined. IL4 significantly inhibited cell growth of all cell lines examined at 100-500 units/ml; but a dose-dependent differential response to individual cell lines occurred. The effect of IL4 was augmented by combination with IFN or TNF. Melanoma-associated ganglioside antigens (GM3, GD3, GM2, GD2) and human leukocyte antigen class I and DR on the cell surface of melanoma cells were assessed by flow cytometry and/or a radiometric binding assay. IL4, IFN, or TNF alone enhanced human leukocyte antigen class I, DR, and beta 2-microglobulin antigen expression. IL4 alone and in combination with IFN or TNF increased the GM3/GD3 ratio expression. GD2 was enhanced significantly by IL4, IFN, and TNF. Pretreatment of melanoma with IL4 or with other cytokines prior to stimulation with peripheral blood lymphocytes significantly enhanced mixed lymphocyte tumor reaction activity as compared with non-treated melanoma used as stimulators. These studies demonstrate that IL4 alone or in combination with IFN and TNF can modulate melanoma growth activity and surface antigen expression to a more differentiated and immunogenic phenotype.

Antigens, Neoplasm

An experimental model for the evaluation of vitrectomy instruments.

A scleral window was designed for implantation in human autopsy eyes. This model provides direct visualization of the pars plana, vitreous base and peripheral retina. Using this model, one can directly observe vitrectomy instruments entering the globe, and can evaluate the cutting ability of a variety of instruments. The model can also be used to provide practical experience, analogous to clinical vitrectomy, and is therefore useful as a training device.

Cadaver

Pseudophakic retinal detachment.

Our experiences with a small group of patients who had intraocular lens implants performed at the time of cataract extraction, and who subsequently developed retinal detachment are reviewed. The technical problems related to retinal detachment surgery in the presence of intraocular lenses and the results of this surgery are summarized.

Adult

Aphakic retinal detachment. Management of the fellow eye.

One hundred eighty-five patients with unilateral aphakic retinal detachment were studied to determine the frequency of retinal detachment in the fellow eyes undergoing cataract surgery. It was found to be four times higher than the frequency in those eyes that remained phakic (26% vs 7%). Despite the high incidence of detachment, 94% of the aphakic group had a final visual acuity of 20/60 or better in the second eye. At the time of surgery, the macula was still attached in only 17% of the 185 first eyes as compared to 57% of the 21 second eyes that developed an aphakic retinal detachment.

Adult

Early photocoagulation treatment of active histoplasmic maculopathy.

Photocoagulation has proved to be an effective means of treating active presumed histoplasmic maculopathy. Xenon arc and argon laser light sources have proved equally effective when moderately intense, confluent burns are produced, and both are ineffective when mild lesions are produced. The membrane must be destroyed for the treatment to be effective; and, of course, the fovea must be preserved. In treating neovascular nets that are very close to the fovea, the argon laser offers the advantage of being capable of producing a sharper zone of delineation than the xenon arc (Fig. 6). When moderate amounts of subretinal fluid or hemoglobin overlie the neovascular membrane, it is very difficult to achieve the required degree of coagulation. Under these circumstances, it is best first to try to reduce the height of the sensory retinal detachment by means of systemic steroid treatment. If this is not successful, xenon photocoagulation has produced better coagulation effects than the argon laser. Analysis of our data indicates that resultant visual acuity can be correlated with pretreatment visual acuity (Fig. 5), with best results achieved before visual acuity deteriorates beyond the 20/40 level. The closer the edge of the neovascular membrane is to the fovea, the more risky it is to treat. However, these lesions are also those most apt to destroy central vision if left alone. It is encouraging to note that in only 3 of the 16 lesions in which the foveal edge was within 1 degree of the fovea did the visual acuity deteriorate to the 20/200 level, compared to 50 percent deterioration reported in the natural history of this disease [3].

Argon

Drainage of subretinal fluid: why, when, where and how.

The release of subretinal fluid is only required in certain complicated types of retinal detachment and should be avoided when possible. An important consideration in releasing subretinal fluid is the timing of this step in relation to the application of diathermy or cryotherapy as the primary treatment modality. Drainage should precede application of cryotherapy but follow the use of diathermy. The most satisfactory site for drainage is either immediately above or below the medial or lateral long ciliary nerve, just posterior to the equator of the globe. A technique for drainage of subretinal fluid has been developed and evaluated. An 'L'-shaped scleral flap is dissected to produce a relatively staphylomatous zone and the choroid is perforated near its center.

Choroid

Intraocular irrigating solutions for clinical vitrectomy.

Two different intraocular irrigating solutions were used during pars plana vitrectomy. Use of glutathione-bicarbonate-Ringer's (GBR) solution resulted in significantly fewer corneal complications and less endothelial damage when compared to lactated Ringer's solution. The visual results were disappointing.

Bicarbonates