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Biomedical subjects

J T Rosenbaum

Publications and source records attributed to J T Rosenbaum.

15 recordsLinked to original sources
PubMed1992

Activity of an interleukin 1 receptor antagonist in rabbit models of uveitis.

Interleukin 1 has been implicated in intraocular inflammation. The availability of a cloned, recombinant interleukin 1 receptor antagonist has enabled us to test the role of interleukin 1 in specific models of uveitis in New Zealand white rabbits. Seventy-five micrograms of interleukin 1 receptor antagonist injected intravitreally resulted in a 97% reduction in aqueous humor cells present 6 hours after intravitreal injection of 10 ng of human interleukin 1 alpha. Disruption of the blood aqueous barrier was prevented by the receptor antagonist (mean +/- SD aqueous humor protein of 0.6 +/- 0.1 g/L in rabbits treated with interleukin 1 receptor antagonist vs 32.2 +/- 9.9 g/L in controls). Lower doses of interleukin 1 produced more modest but significant inhibition. Despite the activity of interleukin 1 receptor antagonist in inhibiting interleukin 1-induced inflammation, interleukin 1 receptor antagonist did not produce significant reduction in inflammation subsequent to an active Arthus reaction or subsequent to the intravitreal injection of 125 ng of endotoxin. A potential explanation of these observations is that cytokines in addition to interleukin 1 may be present in sufficient quantities to produce intraocular inflammation or that the effects of interleukin 1 may be primarily intracellular (intracrine) and therefore resistant to the activity of exogenously administered receptor antagonist.

Animals↗
PubMed1992

Intraocular lymphoma. Immunopathologic analysis of vitreous biopsy specimens.

Immunologic analysis of cell surface markers (immunophenotyping) has become a standard procedure in the evaluation of systemic lymphomas. However, attempts to apply these techniques to intraocular lymphoma have not been uniformly successful. We successfully immunophenotyped five consecutive cases of intraocular lymphoma using immunoperoxidase surface marker analysis of cytocentrifuged specimens in two cases and flow cytometry in three. In all five cases, a monoclonal B-cell population was unequivocally present. Contrary to previous reports, we found surface marker analysis of vitreous biopsy specimens to be helpful in the diagnosis and treatment of intraocular lymphoma. Not only did it support the cytologic diagnosis but it allowed comparison of the immunophenotype of vitreous infiltrates with that of previous or subsequent lymphomatous lesions from nonocular sites.

Aged↗
PubMed1992

Production and modulation of interleukin 6 synthesis by synoviocytes derived from patients with arthritic disease.

Interleukin 6 (IL-6) is a potent cytokine, the biological activities of which include the stimulation of immunoglobulin secretion, T cell activation, induction of the acute phase response, activation of megakaryocytes, and pyrogenicity. These biological activities make it a plausible contributor to rheumatoid arthritis. The ability of synoviocytes to synthesise this potential mediator of inflammation was tested. Cultures of fibroblast-like cells were established from joint tissue from patients with rheumatoid arthritis, degenerative joint disease, or trauma. Supernatants from synoviocytes from each diagnostic category contained IL-6-like activity as detected in a B9 plasmacytoma cell proliferation assay. Supernatants from IL-1 stimulated synoviocytes from patients with rheumatoid arthritis (n = 5) contained an average of 70,000 U/ml IL-6. Western blot analysis confirmed that these supernatants contained peptides that reacted with a highly specific antibody to IL-6. A cDNA probe specific for IL-6 hybridised with mRNA derived from synoviocytes representative of each disease state. Interleukin 6 mRNA expression increased by culturing synoviocytes in the presence of 10% calf serum, IL-1 (30 U/ml), insulin (166 ng/ml), or basic fibroblast growth factor (16 ng/ml). In contrast, dexamethasone (10(-6) mol/l) suppressed the ability of IL-1 to increase the expression of IL-6 mRNA. Recombinant IL-6 itself did not detectably upregulate its own message. The regulation of production of IL-6 by synoviocytes may be important in the pathogenesis of joint inflammation.

Arthritis, Rheumatoid↗
PubMed1992

Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin-1.

Interleukin-6 (IL-6) is a peptide whose properties include the ability to activate T-lymphocytes, stimulate the secretion of immunoglobulin, induce neuronal differentiation, and trigger the release of acute phase proteins. We have detected IL-6-like activity in conditioned medium from cultured human retinal pigment epithelial (RPE) cells with a bioassay based on the ability of IL-6 to induce the proliferation of murine B-9 plasmacytoma cells. Biologic activity increased approximately 90-fold when the cells were cultured in the presence of IL-1 alpha (30 units/ml). Western blot analysis confirmed that conditioned medium from IL-1 alpha-stimulated RPE cells contained peptides with molecular weights ranging between 19,000 and 30,000 and reactive with antibody to IL-6. Finally, Northern blot analysis indicated that cells cultured in the presence of interleukin-1 contained a 1.2 kilobase transcript that hybridized to a cDNA probe specific for IL-6 messenger RNA. IL-6 peptide on Western blots and mRNA on Northern blots were undetectable unless cells were cultured in the presence of IL-1 alpha. Although IL-6 is synthesized by a variety of cell types, this report is the first to detect its synthesis by an eye-specific cell type. Furthermore, these observations indicate that retinal pigment epithelial cells respond to IL-1, a cytokine that previously has been implicated in ocular inflammation.

Blotting, Northern↗
PubMed1992

Reduction of endotoxin-induced vascular permeability by monoclonal antibodies against lipopolysaccharide determinants.

Endotoxin, a bacterial lipopolysaccharide implicated in the pathogenesis of septic shock, markedly alters vascular permeability following intravenous injection in rabbits. We investigated the ability of murine monoclonal antibodies to confer protection against endotoxin-induced increases in a rabbit model of ocular vascular permeability. Four monoclonal antibodies of differing specificities as well as polymyxin B were compared for their effects on endotoxin from either Escherichia coli or Pseudomonas aeruginosa. Preincubation of endotoxin with antibodies directed against Pseudomonas O side chain or core glycolipid resulted in marked attenuation of vascular permeability due to Pseudomonas endotoxin, but not E. coli endotoxin. Antilipid A antibodies were not significantly effective in neutralizing either endotoxin with in vitro preincubation. Low avidity of the antilipid A antibody, low density of lipid A binding sites, or inaccessibility of the lipid A may have prevented more marked interactions. When administered intravenously prior to endotoxin challenge, none of the antibodies demonstrated the ability to provide specific protection to subsequent endotoxin in this model. They did provide partial nonspecific protection against endotoxins regardless of epitope specificity. When administered prophylactically, polymyxin B, an antibiotic that binds to lipid A, was highly effective in neutralizing the toxic effects of endotoxin. Since antibodies to lipid A reduce mortality in septic shock, the failure to demonstrate efficacy in this study may be due to the marked sensitivity of the rabbit eye to endotoxin. Alternatively, beneficial effects from antiendotoxin antibodies in septic shock may be unrelated to the inhibition of vascular permeability. Some protection from antiendotoxin antibodies may be due to enhancement of nonspecific mechanisms.

Animals↗
PubMed1992

Acute anterior uveitis and spondyloarthropathies.

An acute onset, unilateral anterior uveitis occurs during the course of either Reiter's syndrome or ankylosing spondylitis. Conversely, many patients who suffer from an acute anterior uveitis are HLA-B27-positive and have associated joint disease. The consistent presentation of the uveitis can aid in the process of differential diagnosis. This article includes a discussion of the recognition of the characteristic presentation, the complications, the role of B27 testing, the relevance of animal models, the pathogenesis, and treatment.

Acute Disease↗
PubMed1991

Uveitis precipitated by nonpenetrating ocular trauma.

Although penetrating trauma is a well-recognized cause of uveitis, the role of nonpenetrating trauma in initiating uveitis is not defined. We analyzed the records of 496 patients seen at the uveitis clinic at our institution. Twenty-four of these 496 patients (4.8%) suspected that the cause of their intraocular inflammation was related to previous nonpenetrating trauma. In contrast, only one of 251 patients (0.4%) attending the general ophthalmology clinic for routine care provided a history of recent trauma or attributed the present ocular complaint to trauma (P less than .02). Patients with posttraumatic uveitis were usually male (19 of 24, 79%), younger (31 +/- 16 years) than the average patient examined in the uveitis clinic, and more likely to have unilateral disease. In ten (42%) of the patients the trauma was work-related. Bilateral inflammation was seen in eight (one third) of the patients and 17 of 28 patients (71%) had a considerable degree of inflammation posterior to the lens. Many patients had an identifiable cause of uveitis such as ankylosing spondylitis, Reiter's syndrome, sarcoidosis, or acute retinal necrosis; but most patients had no known predisposition. The role of nonpenetrating trauma in initiating uveitis has implications for diagnosis and treatment.

Accidents, Occupational↗
PubMed1991

Systemic sulfonamides as a cause of bilateral, anterior uveitis.

Between September 1976 and May 1989, 12 cases of uveitis attributed to the systemic use of sulfonamide derivatives were reported to the National Registry of Drug-Induced Ocular Side Effects and the US Food and Drug Administration. We evaluated these reports in addition to one case previously reported in the literature and one patient seen at the Uveitis Clinic, Oregon Health Sciences University, Portland. The patients' median age was 34 years. Twelve of 14 patients were treated with trimethoprim-sulfamethoxazole. All patients for whom the location of the eye disease was specified presented with an iritis. Six reports included a description of ocular symmetry, with all patients having bilateral inflammation. Of the nine patients for whom data on the duration of drug use was available, seven experienced adverse effects within 8 days of beginning trimethoprim-sulfamethoxazole therapy and four showed effects within 24 hours. Three patients had histories of rechallenge with trimethoprim-sulfamethoxazole, and in each case acute iritis recurred within 24 hours of reinstitution of therapy. Five patients had additional evidence of an adverse reaction manifested as Stevens-Johnson syndrome, erythema multiforme, diffuse macular or vesicular rashes, stomatitis, glossitis, conjunctival and scleral injection, and granulomatous hepatitis. The consistent presentation including bilateral, anterior inflammation and the recurrence with rechallenge strongly indicate a cause-effect relationship. Although uveitis secondary to sulfonamides is a rarely diagnosed clinical event, recognition of the distinct presentation of this entity is important in the differential diagnosis of uveitis.

Child, Preschool↗
PubMed1991

Synthesis of platelet activating factor by ocular tissue from inflamed eyes.

Platelet activating factors (PAFs) are a family of ether lipids with properties that suggest a major role in inflammation. We have previously implicated PAFs in ocular inflammation based on the inhibition of several rabbit models of iritis with a specific PAF receptor antagonist. We have tested ocular tissues for the ability to synthesize PAF. Iris, ciliary body, cornea, and/or retina were carefully dissected from New Zealand white rabbits, and tissue from four eyes was pooled. Tissues were stimulated with calcium ionophore (10 mumol/L), and supernatants were extracted with chloroform-methanol. Platelet-aggregating activity was found in the chloroform phase in 2 of 9, 1 of 8, 0 of 9, and 3 of 9 studies involving iris, retina, ciliary body, or cornea, respectively. Twenty-four hours after the intravitreal injection of 125 ng of endotoxin, aggregating activity was consistently detectable from supernatants of stimulated iris and ciliary body, occasionally present from stimulated retina but not detectable from cornea. The shape of the aggregation curve resembled that produced by 0.5 to 2.0 ng of authentic PAF. Moreover, the aggregation could be completely inhibited by a PAF receptor antagonist and the aggregating activity chromatographed identically on high-performance liquid chromatography to a PAF standard. These studies indicate that PAF-like activity could be detected from several ocular tissues subsequent to inflammation. Iris, ciliary body, retina, vascular endothelium, and/or leukocytes could each contribute to the presence of this inflammatory mediator.

Animals↗
PubMed1991

Use of a soluble interleukin-1 receptor to inhibit ocular inflammation.

Interleukin-1 (IL-1) has been strongly implicated as an inflammatory mediator in anterior uveitis. Recently, solubilized receptors have been utilized to block the binding of viruses to cell membranes or to inhibit cytokine activity. We have tested the activity of an intravitreally injected soluble, human interleukin-1 receptor in a rabbit model of IL-1-induced inflammation. 3 ug of the soluble receptor markedly inhibited both the cellular infiltration and the protein extravasation that followed 6 hours after an intravitreal injection of 10.5 ng of recombinant human interleukin-1 alpha. The efficacy of the soluble receptor was less marked 24 hours after the IL-1 injection. The cellular infiltrate was not reduced at all if the IL-1 receptor was injected 2 hours after the IL-1. The activity of the soluble receptor deserves further study as a therapeutic modality for inflammatory eye disease.

Animals↗
PubMed1991

Retinal vasculitis--a primer.

Retinal vasculitis is a diagnosis that is generally suggested by an ophthalmologist. Frequently patients with the disorder are referred to nonophthalmologists for further diagnostic evaluation or treatment. The criteria for defining vasculitis differ greatly between ophthalmologists and other physicians. To facilitate collaboration between ophthalmologists and their colleagues, we have sought to clarify the term "retinal vasculitis" by discussing its subcategories, the potential role of antiphospholipid antibodies, and the etiology of retinal vasculitis. We offer guidelines for evaluating the disorder and treating patients.

Humans↗
PubMed1977

The role of IgE in the immune response to neoplasia: a review.

The role of IgE in the immune response to neoplasia has received little attention despite suggestive evidence for an IgE response to tumor specific antigens. A complex interrelationship is known to exist between basophils, eosinophils, histamine, complement, and T cells. The latter cells are known to play a central role in the immune response to neoplasia and, in addition, are now considered important in the production and regulation of IgE, the molecule that may supply an important link between pharmacological and cellular dynamics of a successful anti-tumor response. The evidence for an IgE role in the immune response to tumors, the relationship between atopy and cancer, and the possible mechanisms whereby IgE could enhance tumor rejection are discussed in this review.

Animals↗
PubMed1976

The effect of anti-mu suppression of gammaM and gammaG on the production of gammaE.

Newbonr mice were treated from the day of birth with either bovine gamma globulin or anti-mu chain sera. The latter was administered using a protocol known to produce suppression of gammaM, gammaG, and gammaA production. Subsequent immunization with ovalbumin (OA) in alum was attempted to see if suppression of gammaM, gammaG, and gammaA classes of antibody would also be accompanied by suppression of gammaE-producing capacity. gammaG and gammaM antibody to OA and mercaptoethanol-resistant (gammaG) antibody to OA were measured by passive hemagglutination; gammaG and gammaE anti-OA antibodies were measured by passive cutaneous anaphylaxis. Anti-mu suppression was achieved with significant reduction in gammaM and gammaG antibodies. gammaE antibodies were not affected, suggesting an ontogenetic development for gammaE-bearing lymphocytes independent of the previously described gammaM to gammaG to gammaA ontogenetic sequence.

Animals↗