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Biomedical subjects

R B Nussenblatt

Publications and source records attributed to R B Nussenblatt.

At least 19 recordsLinked to original sources
PubMed1992

An unusually high prevalence of ocular toxoplasmosis in southern Brazil.

Because of the frequency of ocular toxoplasmosis and its occurrence in multiple siblings in southern Brazil, a population-based household survey was performed to better understand the epidemiologic characteristics of the disease in this region. Of 1,042 individuals examined, 184 (17.7%) were deemed to have ocular toxoplasmosis on the basis of conservative assessment of ophthalmic findings. Of those with ocular toxoplasmosis, 183 (99.5%) had specific IgG antibodies, compared with only 140 of 181 age-matched control subjects (77.4%; P less than .001). The prevalence of ocular toxoplasmosis was 0.9% in 1- to 8-year-olds, 4.3% in 9- to 12-year-olds, 14.3% in 13- to 16-year-olds, and 21.3% (95% confidence interval, 18.6% to 24.2%) in all individuals 13 years or older. The prevalence of ocular toxoplasmosis in this population was more than 30 times higher than previous estimates for the same condition elsewhere. The low prevalence in the young children we studied supplements previous data suggesting that, in this population, ocular toxoplasmosis is a sequela of postnatal rather than congenital infection.

Adolescent↗
PubMed1992

Combined use of cyclosporine and ketoconazole in the treatment of endogenous uveitis.

Ten patients with endogenous uveitis were in clinical remission attributable to treatment with cyclosporine and prednisone. After the cyclosporine dose was reduced by two thirds, these patients were randomly assigned to treatment with or without ketoconazole, a potent inhibitor of cytochrome P-450, in a double-masked placebo-controlled study. The dose was reduced over three days. During a three-month follow-up, no patients treated with ketoconazole had a relapse of uveitis, while four of six (66%) control subjects had a flare-up. Toxicity in the ketoconazole-treated group was limited to a transient decrease in glomerular filtration rate (20% from baseline) at one month in two of six (33%) patients. Renal function was stabilized by further reduction of the cyclosporine dose.

Autoimmune Diseases↗
PubMed1992

Retinal toxicity in human immunodeficiency virus-infected children treated with 2',3'-dideoxyinosine.

To assess the safety and antiretroviral activity of 2',3'-dideoxyinosine, we enrolled 43 children with symptomatic (Centers for Disease Control class P-2) human immunodeficiency virus infection in a Phase I-II study and monitored them prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. Follow-up ranged from 12 to 103 weeks with a median follow-up of 71 weeks. Three of 43 children (7.0%) developed peripheral atrophy of the retinal pigment epithelium during treatment with 2',3'-dideoxyinosine. The two children with the most severe retinal atrophy were enrolled in the study at the highest dosage studied (540 mg/m2/day). In contrast to findings in children, no retinal atrophy in HIV-infected adults treated with 2',3'-dideoxyinosine has been evident to date.

Atrophy↗
PubMed1992

Expression of cell adhesion molecules in posterior uveitis.

Cells in the eye express surface molecules that direct leukocyte migration during ocular inflammation. We studied the expression of intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and endothelial leukocyte adhesion molecule-1 in six enucleated eyes from patients with uveitis and in seven normal control eyes. Lymphocyte function-associated antigen-1 was expressed on infiltrating lymphocytes and intercellular adhesion molecule-1 was expressed on endothelial cells of retinal and choroidal blood vessels and the retinal pigment epithelium in all uveitic eyes, but in none of the normal control eyes. Ocular inflammatory cells stained strongly positive for tumor necrosis factor alpha in all eyes with uveitis, but four of six uveitic eyes showed mild staining for tumor necrosis factor beta and interferon gamma. Cell adhesion molecules are expressed in eyes with posterior uveitis and may be regulated by cytokines such as tumor necrosis factor alpha.

Adult↗
PubMed1992

Cellular immune responses to retinal antigens in retinitis pigmentosa.

Patients with retinitis pigmentosa and a group of controls were tested for their cellular immune response toward two retinal proteins, S-antigen and interphotoreceptor retinoid-binding protein (IRBP), as well as their reaction against two synthetic peptides ("M" and "N") derived from the sequence of S-antigen and peptide "R14", derived from IRBP. Positive responses to the retinal antigens were found in larger proportions and with higher levels in the patient group than in the controls. The difference between the two groups was statistically significant in their response to S-antigen, but the patients reacted better than the controls against the other antigens as well. Of particular interest was the finding that several patients responded to both retinal proteins and/or to their peptides. These patients suffered from severe retinal changes and the data are thus interpreted as suggesting that the responses to the retinal antigens are secondary to these changes and to nonphysiological release of retinal antigens.

Adult↗
PubMed1992

Control of experimental autoimmune uveoretinitis by low dose T cell vaccination.

Autoimmune T lymphocytes can be used under appropriate conditions to induce resistance to the specific autoimmune disease that they usually produce. This practice, termed T cell vaccination, was found to be effective with the injection of a low (subpathogenic) number of autoaggressive T line lymphocytes. We report here that T cell vaccination produced marked resistance to the expression of experimental autoimmune uveoretinitis (EAU) in Lewis rats. In addition, vaccination led to the appearance of lymphoid cells in the vaccinated rats that demonstrated proliferative responses against idiotypic and ergotypic specificities of the injected T cells. This is the first report demonstrating the effector T lymphocytes specific for ocular antigens may be used as agents to modulate immunopathogenic responses responsible for EAU.

Amino Acid Sequence↗
PubMed1992

Association between mast cells and the development of experimental autoimmune uveitis in different rat strains.

To study the role of anterior uveal mast cells in experimental autoimmune uveitis (EAU), the mast cells in the iris and ciliary body of Lewis rats, Brown Norway (BN) rats, and their F1 hybrids (LBNF1) were quantitated in normal rats and during the induction period of EAU. The mean baseline mast cell number was 68.9 +/- 10.8 per anterior uvea for Lewis rats, 0.3 +/- 0.2 for BN rats, and 4.6 +/- 0.6 for LBNF1 rats. Detectable mast cells in the anterior uvea of S-Ag-immunized Lewis rats decreased to 60% of control at 6 days postimmunization, recovered to 80% at 10 days, and dropped again to 16% at 13 days, with disease onset around 14 days. In Lewis rats that were adoptively transferred with a uveitogenic T-lymphocyte line, a profound drop in anterior uveal mast cell numbers occurred in the eyes with early signs of EAU, 3 days after the transfer. The decrease in detectable mast cells is consistent with mast cell degranulation. The data suggest that anterior mast cells participate in the immunopathogenesis of EAU and may influence the genetic susceptibility to EAU.

Animals↗
PubMed1992

Predominant usage of V beta 8.3 T cell receptor in a T cell line that induces experimental autoimmune uveoretinitis (EAU).

Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease induced in animals by immunization with retinal proteins (or synthetic fragments derived from them) in adjuvant, and it is considered a model of human autoimmune diseases of the eye. To study the T cell clonotypes that may be involved in EAU, we analyzed the T cell repertoire of three related T cell lines: the pathogenic line LR16, specific to the major uveitogenic epitope of IRBP; its pathogenic subline J; and its nonpathogenic subline A. We examined the expression of the genes coding for the variable regions of the 20 known Lewis rat T cell antigen receptor (TCR) V beta families. The nonpathogenic subline was found to contain mostly T cells expressing V beta 5, V beta 8.2, and V beta 19 while the pathogenic subline consisted mainly of cells expressing V beta 8.3 TCRs. Genomic Southern blot analysis of DNA from the pathogenic subline showed that V beta 8.3-expressing T cells were the dominant clonotype, and DNA sequence analyses of V beta 8.3 cDNAs revealed that two V beta 8.3 TCRs were expressed in the pathogenic subline. One of the V beta 8.3 cDNAs encoded a variable region gene segment identical to previously reported rat V beta 8.3 TCR while the other differed by two amino acids in the second complementarity determining region (CDR2). Taken together with previous data showing overrepresentation of V beta 8-expression in T cell lines that induce EAU, but not in nonuveitogenic T cell lines, our results suggest that V beta 8.3-expressing T cells represent a pathogenic clonotype in IRBP-induced EAU.

Amino Acid Sequence↗
PubMed1992

Enhancement of S-antigen and its mRNA in the irides of uveitic patients.

S-antigen (S-Ag) and its mRNA were analysed by immunohistochemistry and in situ hybridization in 32 iridectomy specimens from 29 uveitic patients and 10 non-uveitic patients. S-Ag was detected in one iris and its mRNA was detected in 12 uveitic patients. Neither S-Ag nor its mRNA was found in the controls (P < 0.003). Ten of the 12 patients who had detectable S-Ag mRNA, while only four of the 17 patients who did not, had received corticosteroids for more than 3 years (P = 0.006). We also demonstrated S-Ag and its mRNA in bovine iris by immunoprecipitation and polymerase chain reaction. These results indicate that S-Ag and its mRNA accumulate in the irides of some uveitic patients. This accumulation may be the result of local immunoregulatory factors and an effect of corticosteroid treatment, and may modulate ocular inflammation.

Adrenal Cortex Hormones↗
PubMed1992

Treatment of aggressive cytomegalovirus retinitis with ganciclovir in combination with foscarnet in a child infected with human immunodeficiency virus.

Ganciclovir and foscarnet are both effective for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome, but the benefits of either agent given alone are limited. A child infected with human immunodeficiency virus who had cytomegalovirus retinitis that progressed despite treatment with either agent alone received the combination of ganciclovir and foscarnet. This treatment resulted in a sustained clinical response.

Antiviral Agents↗
PubMed1992

Immunocytochemical staining of vitreous cells. Indications, techniques, and results.

Diagnostic vitrectomy is often performed because of suspected infection or malignancy. Giemsa, Gram, and Papanicolaou stains are used routinely to identify the components in the vitreous. Immunocytochemical staining of cellular components of vitreous specimens has the potential to significantly increase the amount of useful information that can be gained from histopathologic study. Vitreous specimens from 14 patients undergoing diagnostic or therapeutic vitrectomy for infection, suspected primary intraocular lymphoma, or uveitis were examined by immunocytochemical staining using monoclonal antibodies specific for leukocyte subclass antigens and immunoglobulin. The three classes of disorders showed characteristic patterns of staining, which were useful in confirming microbiologic and clinical diagnoses. Infections showed more pronounced neutrophils and macrophages, primary intraocular lymphomas demonstrated light chain restriction of the malignant B lymphocytes, and uveitis was characterized by the predominance of T lymphocytes. The routine use of immunocytochemical staining is recommended to characterize cellular infiltrates and increase the diagnostic yield from vitrectomy specimens.

Antibodies, Monoclonal↗
PubMed1992

Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid.

It has been hypothesized that coinfection with mycobacteria occurs in patients with Pneumocystis carinii choroiditis, but cases demonstrating ocular infection by both organisms have not been reported. This study reports the case of a patient with P. carinii choroiditis who was treated with intravenous trimethoprim and sulfamethoxazole, followed by intravenous trimethoprim and dapsone. The choroidal lesions failed to resolve despite 6 weeks of treatment, and the patient died from massive pulmonary infection caused by P. carinii, Mycobacterium avium-intracellulare, and cytomegalovirus infections. Ocular histologic and electron microscopic examinations revealed choroidal infection by both P. carinii and M. avium-intracellulare. Serum levels of sulfamethoxazole were below the recommended therapeutic range for treating P. carinii infection during the first week of therapy, but adequate drug levels were subsequently obtained. Failure of choroidal lesions of P. carinii to resolve in some cases may suggest insufficient antimicrobial levels in the blood or raise the possibility of coexistent M. avium-intracellulare or other opportunistic infection.

AIDS-Related Opportunistic Infections↗
PubMed1992

Analysis of autoantibodies among patients with primary and secondary uveitis: high incidence in patients with sarcoidosis.

The sera of 122 patients with uveitis were examined for the presence of various antinuclear autoantibodies. Overall 21.3% of the patients had antibodies to ribonucleoprotein (RNP) and 18% to Ro (SSA). When subdividing the patients according to primary uveitis versus secondary uveitis, the autoantibodies were detected more frequently in the second group [anti-RNP 13.3 vs. 31.4%, anti-Ro (SSA) 11.8 vs. 27.7%, anti-Sm 10.3 vs. 24% and poly (G) 2.9 vs. 14.8%, respectively]. No differences could be asserted in autoantibody frequencies according to disease location within the uvea. Among uveitis patients afflicted with sarcoidosis a particular high incidence of autoantibodies was detected in comparison with all other subgroups of patients with uveitis. Although the presence of autoantibodies among patients with uveitis appears not to have a major diagnostic value, their assessment may aid to a better understanding of disease pathogenesis.

Antibodies, Antinuclear↗