Effect of cobra venom factor on the local GVH reaction. I. Partial characterization of a cytotoxic factor from cobra venom for rat lymphocytes.
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Biomedical subjects
Publications and source records attributed to M Ballow.
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Autoimmune New Zealand (NZ) mice exhibit a broad spectrum of T and B cell disorders. These include abnormally high levels of terminal deoxynucleotidyl transferase-positive immature T cells in bone marrow and thymus. We have shown previously that prostaglandin E1 (PGE1) treatment of the NZB/NZW F1 hybrid, a murine model of systemic lupus erythematosus (SLE), reduces to normal the percentage of immature terminal deoxynucleotidyl transferase-positive cells in bone marrow and thymus, and prevents the immune complex-induced nephritis which kills these animals. We report here that short-term (1-5 days) treatment of NZB/W mice with PGE1 increases thymocyte responsiveness to mitogens and alloantigens. The majority (greater than 90%) of cortical thymocytes agglutinated by peanut lectin (PNA+) are depleted by PGE1 treatment. However, a small population of highly functional cells persists in the PNA+ fraction after PGE1 treatment. PGE1 appears to have little or no effect on the PNA-negative (medullary) fraction of thymocytes. Our data suggest that PGE1 may exert its therapeutic effect in NZ mice by increasing the functional maturity of immature T cells.
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BACKGROUND: Retinoic acid (RA) has important immune-modulating effects on both T and B cell function. Our laboratory has shown that RA can enhance in vitro polyclonal B cell immunoglobulin (Ig) response. Investigating cytokines known to affect B cell differentiation, we have recently shown that IL-6 production is augmented by RA. In the present study we have examined the immune modulating effects of RA on IL-2 mRNA, another important cytokine for B cell immunoglobulin production, the expression of IL-2 receptors on T cells, and the RA nuclear receptors. METHODS: Purified T cells were obtained from adenoidal tissues, and incubated with RA (10(-7) M) or DMSO solvent/media control for 0, 6-8, and 24 h. Total mRNA was extracted from T cells, and using RT-PCR, changes in the production of IL-2 and RA receptors (RAR)-alpha,beta,gamma mRNA were determined. The effects of RA on IL-2-alpha receptor expression was determined by flow cytometry on T cells. CONCLUSION: These studies suggest that RA can augment IL-2 mRNA production by T cells with a possible paracrine effect on IL-2R-alpha expression. These changes appear to be mediated by RAR-alpha. Thus, IL-2 may be another important cytokine modulated by RA in the immune response.
Eighty-six children with chronic sinusitis, documented by x-ray with symptoms and signs for more than 12 weeks, were evaluated for atopy and B-cell immune abnormalities. Twenty-nine percent (25/86) of the patients had some B-cell abnormality of immunoglobulin isotype, IgG subclass, and/or hyporesponsiveness to pneumococcal polysaccharide (PPS) vaccine (Pneumovax). Eleven of 17 patients who were hyporesponsive to PPS vaccine had normal immunoglobulin isotypes and IgG subclasses. Twenty-six of these 86 children were followed prospectively for > or = 1 year on prophylactic antibiotics. The 12-month period before the use of prophylactic antibiotics was taken as the control period for each child for comparison. Nineteen of 26 (74%) children had a good outcome (greater than a 50% reduction in the number of exacerbations of sinusitis during a 12-month period compared with the previous year) on prophylactic antibiotics with a reduction in exacerbations of sinusitis from 9.8 per year to 2.7 episodes per year. In contrast, 7/26 had a poor outcome (p < .0001) on prophylactic antibiotics (from 12.6 per year to 8.7 per year on prophylactic antibiotics). There were no significant differences in age, gender, atopy, or presence of a B-cell immune abnormality in the good versus the poor outcome groups to prophylactic antibiotic therapy. Treatment outcome correlated inversely with the number of sinus infections before prophylactic antibiotics, p = .036. Underlying B-cell immune abnormalities could not be correlated with intervention outcome on prophylactic antibiotics. The use of prophylactic antibiotics was an effective treatment modality in children with chronic sinusitis, even in patients with selective immune abnormalities.
The clinicopathologic findings in contact lens-induced giant papillary conjunctivitis (GPC) suggest that the syndrome is the result of a complex immunological process, an idea supported by the presence of elevated tear concentrations of IgG and IgE in GPC. Several groups of investigators have proposed that GPC may be due, in part, to the coating of the contact lens. To test this hypothesis we undertook development of an animal model of GPC in cynomolgus monkeys. Two soft contact lenses from patients with GPC, two from asymptomatic contact lens wearers, and two clean, unused lenses were each placed in one eye and held in place with a partial tarsorrhaphy. Tears from the two monkeys with GPC lenses showed increased levels of IgG (43 +/- 10 micrograms/mL), IgA (54.3 +/- 12.8 micrograms/mL) and IgE (7.7 +/- 3.3 IU/mL) 35-75 days post-lens placement. While the tears from the two monkeys with clean lenses, and the two monkeys with lenses from asymptomatic contact lens wearers had elevated levels of IgG compared to the contralateral control eye without a lens, the tear IgE levels remained normal. Histopathology studies of tarsal conjunctival biopsy material from the monkeys with GPC lenses showed an intense round cell infiltrate at the epithelial-stromal junction. Mast cells were seen in the epithelial layers. These studies suggest that some factor (or factors) in the lens coating from GPC patients was able to induce a local tear IgE response and histopathological changes in monkeys. These changes are similar to the histopathological and immunological findings in human patients with GPC.
We measured tear lysozyme by a radial immunodiffusion assay in patients with contact lens induced giant papillary conjunctivitis (GPC) and in patients with vernal conjunctivitis (VC). The VC and GPC patients had normal levels of tear lysozyme when compared to control individuals who did not have eye disease and to normal individuals who wore contact lenses without difficulty. In contrast, the tear concentration of lactoferrin (another important tear protein produced by the lacrimal glands) was reduced both in VC and GPC patients. Normal levels of tear lysozyme in the presence of reduced tear concentrations of lactoferrin may be a unique pattern in these two ocular conditions. The reduced tear levels of lactoferrin are probably not related to lacrimal gland dysfunction but to other factor(s) important in the pathogenesis of these two ocular disorders.
A patient with metastatic melanoma developed symmetric miliary infiltrates of the lungs while receiving injections of MER into tumor containing lymph nodes of the groin. Open lung biopsy identified the pulmonary lesions as caseating epithelioid granulomas. After cessation of MER therapy, the pulmonary lesions regressed spontaneously. The possible etiology of this so-far-unreported complication of MER therapy was briefly discussed.
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