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Biomedical subjects

J C Waldrep

Publications and source records attributed to J C Waldrep.

52 records · Page 3Linked to original sources
PubMed1983

Anterior chamber associated immune deviation induced by TNP-splenocytes (TNP-ACAID). I. Systemic tolerance mediated by suppressor T-cells.

The relationship between the anterior chamber (AC) of the eye and the immune system was studied after intracameral inoculation with the hapten TNP. Injection of syngeneic TNP-modified splenocytes (TNP-Sp) into the AC of Balb/c mice results in suppressed systemic cell-mediated immunity to TNP as determined by the ear swelling assay. This aberrant immune responsiveness following AC injection of TNP-Sp has been termed TNP anterior chamber-associated immune deviation or TNP-ACAID. The phenomenon of TNP-ACAID is mediated by antigen-specific efferent suppressor T cells (Ts). The generation of Ts in TNP-ACAID requires a period of interaction between the intact eye and spleen, ie, the splenocameral axis.

Animals↗
PubMed1983

Cyclophosphamide-sensitive contrasuppression in TNP-anterior chamber associated immune deviation (TNP-ACAID).

Injection of trinitrophenyl (TNP)-modified splenocytes (TNP-Sp) into the anterior chamber of the eye results in systemic tolerance to TNP, a phenomenon termed anterior chamber associated immune deviation (TNP-ACAID). Two distinct suppressor pathways develop after the induction of TNP-ACAID. The primary suppressor pathway (I) is antigen-specific, is mediated by a cyclophosphamide (Cy)-sensitive suppressor T cell (Ts-I), and requires a Cy-sensitive auxillary cell. The secondary suppressor pathway (II) is antigen nonspecific, is mediated by a Cy-resistant suppressor T cell (Ts-II), and requires a TNP-pulsed accessory macrophage. Suppression via pathway II is demonstrable only when Ts-I cells are functionally inactivated by Cy. Furthermore, the addition of T cells from Sp containing active Ts-I inhibits Ts-II. This suppression of a suppressor cell (i.e., contrasuppression) is mediated by either Ts-I or a third T cell population, which is also Cy sensitive.

Animals↗
PubMed1983

Anterior chamber-associated immune deviation induced by TNP-splenocytes (TNP-ACAID). II. Suppressor T-cell networks.

Injection of trinitrophenyl (TNP)-modified splenocytes (TNP-Sp) into the anterior chamber (AC) of the eye results in systemic tolerance to TNP, a phenomenon termed "AC-associated immune deviation" or "TNP-ACAID". The systemic tolerance of TNP-ACAID is mediated by splenic suppressor T cells (Ts) that comprise an immunoregulatory network made up of two functionally distinct subsets (Ts-I and Ts-II). Ts-I is antigen-specific and cyclophosphamide (Cy)-sensitive, and requires a Cy-sensitive auxiliary cell. Conversely, Ts-II is antigen-nonspecific and Cy-resistant, and requires a TNP-derived accessory macrophage. Suppression via Ts-II is demonstrated only when Ts-I cells are inactivated functionally by Cy. Ts-II cells are regulated by T cells isolated from splenocytes containing active Ts-I suppressors. This contrasuppressive activity is mediated by Ts-I, or perhaps by a third T-cell subpopulation. The relationship between the two suppressor pathways in TNP-ACAID is discussed.

Animals↗
PubMed1983

Human mononuclear phagocyte-associated antigens. III. Relationship of cell surface antigen phenotype between cultured monocytes and tissue macrophages.

In order to determine the correlation between the in vitro model of monocyte differentiation and its in vivo counterparts, cell surface phenotypes of monocytes in culture and mature tissue macrophages were analyzed using monoclonal antibodies, M1/70, TA-1 anti-HLA-DR, and a heteroantisera prepared to macrophage cell line U937. Following 7 days in culture the reactivity of monocytes with M1/70 diminished from 70 +/- 9% to 31 +/- 8%. Similarly, the reactivity to TA-1 dropped from 88 +/- 8% to 23 +/- 7% and for anti-DR, from 79 +/- 5% to 41 +/- 16%. Reactivity with anti-U937 remained unchanged. This altered phenotype of cultured monocytes was found to approximate that of resident splenic macrophages (MO). In addition, freshly isolated monocytes and peritoneal exudate MO (PEMO) were found to be functionally similar in their inability to phagocytize via the C receptors. These results suggest that PEMO arriving recently into the peritoneal cavity from peripheral blood may be midway in transition between monocytes and mature MO, and that the phenotype and functional changes attributed to monocytes in culture may reflect changes that occur in vivo in the transition to tissue MO.

Antigens, Surface↗
PubMed1981

Serological characterization of antibodies eluted from chronically rejected human renal allografts.

Serum samples collected pre- and post-transplant nephrectomy were screened for alloreactive lymphocytotoxins. Three patients demonstrated circulating anti-B cell antibodies with markedly increased cytotoxicity titers after nephrectomy, suggesting that there was active binding of antibodies within the renal allograft. Two of the postnephrectomy serum samples after absorption with platelets and B cells reacted by immunofluorescence with cultured primary kidney cells but not against B or T cells from the same donor. To clarify further the role of such alloreactive antibodies, eluates were prepared from 14 rejected renal allografts and were analyzed for reactivity to cultured primary kidney cells against different leukocyte targets and endothelial cells. Reactivity toward B cells and kidney cells was demonstrated with 80% of the eluates. Absorption experiments of the positive eluates demonstrated multiple types of alloreactive antibodies. In addition to anti-DR activity, eluates had antibodies reactive to kidney cell antigens, monocytes, macrophages, endothelial cells, and polymorphonuclear leukocytes. The demonstration of multispecific alloantibodies in eluates of rejected kidneys is consistent with an important role(s) in maintenance and/or rejection of the kidney allograft.

Antibody Specificity↗
PubMed1981

Polyclonal immunoglobulin synthesis induced by a macrophage factor acting via T cells.

New Zealand White rabbits were killed 7 days after immunization with 1 mg of alum precipitated, keyhole limpet hemocyanin (KLH) into each hind footpad and 3 days after intraperitoneal injection of thioglycollate. When supernatants from cultures of purified, elicited macrophages were added to Mishell-Dutton cultures of primed popliteal lymphocytes, they induced synthesis of both general immunoglobulins and antibody specific for KLH. The active factor(s), polyclonal lymphocyte activator (PLA), appears to be a glycoprotein with a molecular weight between 150,000 and 200,000 daltons. Absorption with high concentrations of thymocytes but not bone marrow cells removed polyclonal stimulatory activity from peritoneal macrophage supernatants which contained PLA. Purified lymph-node B cells were stimulated by PLA only in the presence of T cells. In addition, supernatants from PLA activated, washed T cells were effective at inducing polyclonal B-cell activation. Thus, PLA appears to act indirectly on B cells by stimulating T cells to produce a soluble factor which induces polyclonal B-cell activation.

Adsorption↗
PubMedDate not supplied

Gene transfer by guanidinium-cholesterol: dioleoylphosphatidyl-ethanolamine liposome-DNA complexes in aerosol.

BACKGROUND: A major challenge of gene therapy is the efficient transfer of genes to cell sites where effective transfection can occur. The impact of jet nebulization on DNA structural and functional integrity has been problematic for the aerosol delivery of genes to pulmonary sites and remains a serious concern for this otherwise promising and noninvasive approach. METHODS: This study examined effects of cationic liposome-DNA formulation on both transfection efficiency (in vitro and in vivo) and jet nebulizer stability. The effects of nebulization and sonication on liposome-DNA particle size characteristics were examined. Electron microscopy of promising formulations was performed using several fixation methods. RESULTS: The cationic lipid bis-guanidinium-tren-cholesterol (BGTC), in combination with the neutral co-lipid dioleoylphosphatidylethanolamine (DOPE), was found to have a degree of stability adequate to permit effective gene delivery by the aerosol route. Optimal ratios of lipids and plasmid DNA were identified. Particle size analysis and ultrastructural studies revealed a remarkably homogeneous population of distinctly liposomal structures correlating with the highest levels of transfection efficiency and nebulizer stability. CONCLUSIONS: Optimizing gene delivery vectors for pulmonary aerosol delivery to respiratory sites must take into account factors other than transfection efficiency in vitro. Effects of liposome-DNA formulation on liposomal morphology (i.e. particle size, multilamellar structure) appear to be relevant to stability during aerosolization. These studies have allowed us to identify formulations that hold promise for successful clinical application of aerosol gene delivery.

Aerosols↗
PubMedDate not supplied

Retinal neovascularization associated with acute retinal necrosis.

Unilateral acute retinal necrosis (ARN), developed in a previously healthy 17-year-old boy. Neovascularization of the retina and optic disc was observed when the opaque vitreous was removed by pars plana vitrectomy. Following surgery there was a rapid resolution of neovascularization suggesting that intraocular inflammation, rather than retinal ischemia, was the cause of new vessel formation. Analysis of vitreous mononuclear cells with monoclonal antibodies and the fluorescence-activated cell sorter (FACS) revealed mostly T cells; a pattern consistent with intraocular infection as the cause of ARN. The pathogenesis of intraocular infection is complex and some patients with ARN may be helped by systemic immunosuppression (ie, corticosteroids).

Acute Disease↗
PubMedDate not supplied

Temporal analysis of retinal function in IRBP peptide-induced experimental autoimmune uveoretinitis (EAU).

Experimental autoimmune uveoretinitis (EAU) induced by interphotoreceptor retinoid binding protein (IRBP) is a complex and multifaceted disease mediated by several different immunopathogenic processes. There is a temporal progression of the disease affecting the anterior and posterior segments of the eye, culminating with destruction of the photoreceptor cells. In the present study, we investigated the effects of IRBP peptide-induced EAU on different cell types within the retina. The Muller cells of the peripheral retina are damaged at the onset of EAU at day 9. There is induction of glial fibrillary acidic protein (GFAP) in the peripheral retinal Muller cells with concomitant reduction in the electroretinogram (ERG) b-wave. By day 12 of EAU, intensely GFAP-positive Muller cells are detected throughout the peripheral and central retina and with maximal diminution of the ERG b-wave. There is a lag in the diminution of the ERG a-wave, first detected at day 12 of EAU, and reaching its maximum at day 15. This change in the ERG is associated with destruction of the tips of the photoreceptor cells. These results indicate that during IRBP peptide-induced EAU, there is a positive correlation between the temporal changes in retinal histology, GFAP expression by Muller cells, and loss of retinal function.

Amino Acid Sequence↗
PubMedDate not supplied

Characterization of human IgG subclasses within intraocular compartments.

Multiple factors regulate the distribution of the human immunoglobulin (Ig) G1-4 subclasses within different compartments of the human eye. An experimental protocol was developed for analysis of IgG1-4 using a combination of high pressure liquid chromatography (HPLC) chromatofocusing and an enzyme-linked immunosorbent assay (ELISA). IgG in the human cornea, aqueous humor, and vitreous was extracted and fractionated by chromatofocusing in a pH 9.0-6.0 gradient. A monoclonal antibody based capture-type ELISA was used to determine the IgG1-4 subclass distribution within the fractions. Histograms generated were then used to determine the IgG1-4 subclass profile for each intraocular compartment. Results indicate that the IgG species are similar but unique for each compartment. In contrast to the distribution for normal serum/plasma IgG1-4, the intraocular profiles were extremely heterogeneous and variable. These results indicate that the intraocular compartments are in a state of disequilibrium. There are apparently both common and unique factors that regulate the distribution of individual IgG subclass species for each intraocular compartment. In addition to differences in fluid dynamics, tissue biochemistry, and barrier properties, parameters, unique to the IgG subclass species may also profoundly effect intraocular localization and retention.

Adult↗