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Biomedical subjects

R M Franklin

Publications and source records attributed to R M Franklin.

At least 55 records · Page 3Linked to original sources
PubMed1986

Autoantibodies in humans with cystic or alveolar echinococcosis.

Sera from 16 echinococcosis patients were analyzed with respect to polyclonal B cell activation and autoantibody formation. At least 8 of the sera were from patients who were never in tropical countries and therefore their cases were not complicated by other parasitic diseases. In comparison with a group of 52 healthy controls, these patients had significant levels of antibodies to DNP and haemocyanin, indicators of polyclonal B cell activation. There were also significant differences between control and patient groups with respect to antibodies to dsDNA, histones, actin, vimentin, and desmin. This is the first report of autoantibodies in echinococcosis.

Adolescent↗
PubMed1986

Autoantibodies in Burkitt's lymphoma patients from the Ugandan prospective study.

Pre- and post syndrome sera from five Burkitt's lymphoma patients who partook in the Ugandan prospective study (A. Geser et al., Int. J. Cancer 29 (1982) 397-400) were investigated with respect to autoantibodies. Neighbours and siblings of these patients served as controls and all of these groups were compared with sera from 50 Caucasian normal controls (CNC). Antibody levels significantly higher than those in CNC were found in all African groups for actin, desmin, vimentin, tubulin, keratin, laminin, and collagen type I. Polyclonal B-cell activation, as measured by antibodies to DNP, and high levels of antibodies to P. falciparum were also found. Anti-DNP and antibodies to malaria were also present in sera from our earlier study on Burkitt's lymphoma (E. Vainio et al., Clin. exp. Immunol. 54 (1983) 387-396). Whereas EBV infected B cells do produce autoantibodies, there is a potentiation of autoantibody formation as a result of infection with malaria, which seems to provide an independent trigger of polyclonal B cell activation. This latter event might be one of the factors which results in a correlation of Burkitt's lymphoma with malaria endemic regions.

Adolescent↗
PubMed1985

Effect of avian osteopetrosis virus infection on cells and their collagen synthesis in vitro.

Primary avian tendon fibroblasts and calvarial osteoblasts were infected with the avian osteopetrosis virus MAV.2-O, in vitro. The infected tendon cells could be cloned in soft agar and kept in culture for at least 25 passages, a number not reached by uncloned infected cells. In contrast to many other virus-transformed fibroblasts, these cells continued making collagen and fibronectin, and there were no gross morphological changes as observed in the light microscope. Changes were seen in their cytoskeletal structure, however, as observed by immunofluorescence. The cloned cells were not tumorigenic in nude mice, nor had they an altered pattern of protein phosphorylation. MAV.2-O-infected fibroblasts and the cloned cells synthesized 2-3 times more collagen type I, the main product of their biosynthetic machinery, than control cells. The proportion of the total cellular RNA consisting of specific mRNAs for the precursor of collagen, procollagen pro-alpha 1 and pro-alpha 2 chains, was higher in the infected cells than in normal fibroblasts. Southern blotting experiments indicated that there was no rearrangement of the collagen genes after infection with this virus. Furthermore, large viral DNA fragments were not integrated into the immediate vicinity of the 5' end of the alpha 2-collagen gene.

Animals↗
PubMed1985

Mott cells are plasma cells defective in immunoglobulin secretion.

Plasma cells containing intracellular inclusions of immunoglobulin (Russell bodies) are known as Mott cells, and are found in large numbers in lymphoid organs in autoimmune mice. Hybridoma technique was used to produce cell lines of this phenotype by fusing spleen cells from a NZB mouse with a nonproducing hybridoma cell line (Sp2/0-Ag14), allowing us to carry out studies of this cell type at the biochemical level. Ultrastructurally the inclusions were distended cisternae of rough endoplasmic reticulum, suggesting a block in the secretory pathway of the cells. Biosynthetic labeling studies confirmed that these cell lines have either a complete or partial block of secretion of immunoglobulin, possibly due to an abnormal light chain.

Animals↗
PubMed1985

Developmental and molecular aspects of nephroblastomas induced by avian myeloblastosis-associated virus 2-O.

Avian myeloblastosis-associated virus-induced nephroblastomas are tumors consisting mainly of mesenchymal and epithelial renal elements with variable degrees of differentiation. The spatial distribution of developmental stages reflects a gradient of differentiation from less differential structures in the periphery towards more differentiated structures in the center of the lobules formed in the nephroblastomas. These heterogenic tumors contain discrete virus-cell DNA junction fragments and are therefore clonal outgrowths of a single transformed cell. These findings support the hypothesis that a mesenchymal, nephrogenic cell residual in the postembryonic kidney is the origin of the tumor, which grows by proliferation and differentiation of this target cell. All the tumors expressed higher levels of viral genomic and env messages than nontransformed tissue from the same kidney. A screening of oncogene expression with 13 different oncogenes revealed enhanced myc levels. There was, however, no rearrangement of c-myc or of the other oncogenes detected with EcoRI-digested tumor DNAs. This suggests that there is no insertion of viral elements adjacent to a c-myc. The levels of myc expression in embryonic kidneys were as high as in the tumors. Therefore, the enhanced myc expression in nephroblastomas is a reflection of the embryonic status of the tumor rather than a newly acquired function. This finding, plus the similarity of development and morphology of nephroblastomas and embryonic kidneys, suggests that the tumors arise as a result of a deficiency in a function which turns the embryonic status off.

Animals↗
PubMed1985

Reversal of T-cell unresponsiveness by T-cell-conditioned medium in retrovirus MAV-2-O-induced immunosuppression in chickens.

Polyclonal activation of T-cells with concanavalin A has been used as an in vitro test system to study immunosuppression induced by the avian retrovirus MAV-2-O. The mitogenic responsiveness of peripheral blood lymphocytes from infected chickens was only weakly suppressed, that of spleen lymphocytes was highly suppressed. Addition of conditioned media rich in T-cell growth factor (TCGF) activity to cultures of infected birds resulted in a reconstitution of the suppressed mitogenic responsiveness up to the level found in lymphocyte cultures from normal chickens. This indicates that the defect of the observed immunopathology is not at the level of responding T-cells. Measurements of TCGF production always showed reduced TCGF levels in the suppressed cultures suggesting that there is a defect at the TCGF production level. This is further supported by the failure to reconstitute the suppressed mitogenic response with normal macrophages, which are involved in activation of TCGF producer T-cells.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Lacrimal gland-directed B cell responses.

Although it is accepted that IgA plasma cells predominate in the lacrimal gland, the factors leading to this prevalence are not known. A series of 4-day LPS-driven co-culture experiments performed with dissociated lacrimal gland and lymphoid cell populations was employed to study the direct effect of lacrimal gland cells on B cell differentiation. Lacrimal gland cells, when co-cultured with spleen or mesenteric lymph node cells, were found to suppress differentiation of cells to IgA, IgG, and IgM production. Furthermore, suppression of IgG and IgM responses occurred after co-culture of lacrimal gland cells with Peyer's patch cells. However, these Peyer's patch co-cultures led to a stimulation of the IgA response, a condition that was abrogated by removal of Peyer's patch T cells before co-culturing. Pretreatment of lacrimal gland cells with mitomycin C eliminated the suppression and stimulation previously observed. These results demonstrate the effects of lacrimal gland, both directly and indirectly through T cells, on B cell differentiation. These findings explain in part the preferential accumulation of IgA-plasma cells within the gland.

Animals↗
PubMed1984

Immunohistochemistry on semi-thin sections of hydroxypropyl methacrylate embedded tissues.

Hydroxypropyl methacrylate formulations for embedding hard or soft tissues are described. Dehydration, infiltration and embedding are carried out at 0-4 degrees C. Semi-thin serial sections may be stained by various techniques, including immunohistochemical and enzyme histochemical procedures. Lymphoid tissues and the detection of surface antigens may present some special problems, however, and these are discussed.

Acrylates↗
PubMed1984

A monoclonal antibody recognizes an epitope common to an avian-specific nuclear antigen and to cytokeratins.

X3, a monoclonal antibody of unusual specificity, is described. This antibody reacts with one or more cytokeratin polypeptides and also reacts with an avian (chicken, quail) nuclear antigen that appears to be present in all cell types (chicken) tested, although with variable staining pattern and intensity. This antigen is distinct from the cytokeratins but does have an epitope in common with this class of proteins. It disappears from the nucleus during the early stages of cell division and reappears during anaphase as a granular cytoplasmic structure. In late telophase the antigen is relocated in the nucleus. This antigen, which we have designated as avian-specific nuclear antigen ( AVNA ), is not associated with chromatin or ribonucleoproteins. From immunoblotting experiments on chicken fibroblast nuclei, AVNA is probably a complex composed of one or several polypeptides, one of which has a molecular weight of approximately 60 kD. The proteins were identified as nuclear matrix proteins rather than pore complex-lamina proteins by immunoblotting experiments on the purified nuclear matrix of chicken erythrocytes. The major polypeptide had a molecular weight of 60 kD and the minor polypeptide a molecular weight of 69 kD.

Animals↗
PubMed1984

Lymphocyte migration into the lacrimal gland is random.

The murine lacrimal gland demonstrates a high proportion of both IgA-producing cells and IgA-bearing cells, an observation consistent with tissues of the secretory immune system. This selective accumulation of IgA cells in the lacrimal gland was studied by observing the accumulation of various populations of fluorescein isothiocyanate-labeled lymphocytes in the gland. Labeled spleen cells were found to accumulate equally as well as mesenteric lymph node cells. T cells and T-cell-depleted populations of lymphocytes from spleen also showed migration into the gland. Surface staining of labeled cells found in the gland after 24 hr revealed that IgA-, IgG-, and IgM-bearing cells were all present in high proportions. These experiments demonstrate a random migration of lymphocytes into the lacrimal gland and suggest that the accumulation of IgA-bearing cells in the gland is regulated by the nonvascular microenvironment within the gland.

Animals↗
PubMed1984

The age-dependent size distribution of chicken peripheral blood cells analyzed by a novel method utilizing a Coulter counter.

In a dilute solution of Tris-buffered ammonium chloride (TAC), chicken erythrocytes (RBC) swell but chicken white blood cells (WBC) do not. This allowed us to separate the peaks of RBC and wBC into widely separate channels using a Coulter Counter interfaced to a microcomputer to provide size distributions. Analyses of buffy coat by this technique were carried out on Brown Leghorn chickens from 1 to 21 weeks after hatching. The WBC population, which is chiefly composed of peripheral blood lymphocytes, increased in number from 2 to 7 weeks after hatching, but decreased in size continuously up to the end of the experiment at 21 weeks. The RBC count increased from 2 to 5 weeks after hatching and the size decreased up to 5 weeks after hatching, thereafter remaining constant.

Age Factors↗
PubMed1984

Conjunctival-associated lymphoid tissue: evidence for a role in the secretory immune system.

A specialized lymphoid tissue in rabbit conjunctiva was studied by various histologic and immunologic techniques and compared with similar structures along other mucosal surfaces. The flattened conjunctival lymphoepithelium overlying the lymphoid follicles was devoid of goblet cells. This lack of goblet cells is characteristic of epithelium overlying similar lymphoid collections in gut and bronchus. The lymphoid follicles demonstrated neither intra- nor extracellular immunoglobulin, and the lymphocytes in these follicles were composed of B-cells and T-cells, when studied by various immunologic techniques. A high proportion of these lymphocytes showed surface immunoglobulin A (IgA), and a high proportion of IgA precursors were determined by pokeweed mitogen (PWM) stimulation in 4-day cultures. The morphologic and immunologic results are similar to those obtained from gut and bronchus, tissues known to disseminate lymphoid cells to other mucosal sites already committed to antigen and IgA isotype. It is speculated that conjunctival associated lymphoid tissue of rabbit is part of a generalized system of secretory immunity capable of sampling conjunctival applied antigen, and then disseminating cells committed to IgA antibody production to other mucosal sites.

Animals↗
PubMed1983

Antibodies against conjunctival basement membrane zone. Occurrence in cicatricial pemphigoid.

Antibodies against conjunctival basement membrane zone (BMZ) were found in the serum of six of 12 patients with cicatricial pemphigoid. The ability to detect antibodies correlated with the degree of clinical activity. Each of four patients with active manifestations of the disease was found to have antibodies against BMZ, while only two of the remaining eight patients in a less active stage of the disease demonstrated specific antibodies. Specific circulating serum antibodies are a manifestation of cicatricial pemphigoid, but such antibodies are more easily detected during active disease. Antibodies against BMZ are frequently observed in patients with bullous pemphigoid, a nonocular bullous disease in which circulating antibodies react with a specific skin antigen localized to the lamina lucida, a portion of the BMZ. Therefore, cicatricial pemphigoid and bullous pemphigoid may have a similar pathogenesis.

Antibodies, Anti-Idiotypic↗
PubMed1983

Characterization of chicken T cell growth factor.

Chicken spleen and peripheral blood lymphocytes were tested for their ability to produce T cell growth factor (interleukin 2, IL 2) upon stimulation with phytohemaglutinin or concanavalin A (Con A). Using a qualitative microassay, peak activity was found in 24-h supernatants of mitogen-stimulated lymphocytes. These supernatants permitted continuous growth of chicken lymphocytes for several weeks and increased the Con A response of chicken thymocytes. A quantitative probit microassay was developed and used in the further studies when appropriate. Chicken IL2 binds specifically to thymocytes and activated T cells and its action upon T blast cells cannot be blocked by cyclosporin A. The molecular weights of the two biological active peaks found by gel filtration of the native IL2 preparation were in the range 19500-21500 and 9000-11500. A single polypeptide of molecular weight 13000 was found by gel electrophoresis under reducing conditions.

Animals↗
PubMed1983

Ocular manifestations of graft-vs-host disease.

In patients who have graft-vs-host disease (GVHD) after bone marrow transplantation, ocular involvement occurs in approximately 60% of cases. Among 13 such GVHD patients, the most frequent ocular manifestations included keratoconjunctivitis sicca, cicatricial lagophthalmos, and sterile conjunctivitis and uveitis. The severe ocular complications of persistent corneal epithelial defects and both noninfected and infected stromal ulceration were related to the concomitant dry-eye condition and could be managed by conventional therapy including topical lubricants and antibiotics, punctal occlusion, bandage soft contact lenses, tarsorrhaphy, tissue adhesive, conjunctival flap, and conjunctival homograft. Postmortem and surgical tissues from four patients revealed conjunctival and corneal epithelial thinning and keratinization, lacrimal inspissation without inflammatory infiltration, and diffuse choroiditis. Keratoconjunctivitis sicca in GVHD patients might be a combined result of drug toxicity effects and GVHD. The frequent and potentially severe ocular problems in these patients suggest that close ophthalmic monitoring is mandatory in bone marrow transplant recipients.

Adolescent↗
PubMed1983

Monoclonal antibody which recognizes a common antigenic determinant on intermediate filament proteins, actin, and myosin.

A monoclonal antibody is described which reacts with the intermediate filament proteins vimentin, desmin, keratins, actin, and myosin. This is the first report of an epitope common to intermediate filament proteins and myosin. X1, the wide-spectrum monoclonal antibody in question, was isolated in the course of screening monoclonal antibodies to chicken thymocytes. Cross-reactivities were investigated by immunofluorescence on various types of cultured cells and sectioned tissues, ELISA with a panel of purified antigens, immunoprecipitation, immunodot tests, and immunoblotting.

Actins↗