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Biomedical subjects

S Sell

Publications and source records attributed to S Sell.

At least 145 records · Page 8Linked to original sources
PubMed1983

Malignant rabbit fibroma virus causes secondary immunosuppression in rabbits.

Shope fibroma virus (SFV) causes a localized, self-limited, fibroblastic proliferation in adult rabbits. Extracts of Shope fibroma tumors were found to contain a second virus that induces a rapidly progressive disseminated tumor. Dissemination of this malignant fibroma is associated with activation of commensal mucosal infection with Pasteurella multocida, causing purulent conjunctivitis and rhinitis and resulting in death from nasal obstruction. We have isolated this new agent by two cycles of plaque purification. It is a poxvirus that is antigenically virtually identical to SFV as measured by a plaque reduction assay, but behaves differently both in vivo and in vitro. We have called this virus malignant rabbit fibroma virus (MV). Electrophoresis of restriction digests made with HIND III indicates that despite the antigenic similarity of SFV and MV, the locations of HIND III sites in the two viral genomes are quite different. These experiments have enabled us to determine that MV was present in small quantities in our initial uncloned stock of Patuxent strain SFV. Lymphocytes from rabbits bearing MV-induced tumors responded poorly to both B and T lymphocyte mitogens. This nonspecific immunologic dysfunction is evident at or before the time when metastases and Gram-negative infection develop, and it becomes more profound as the disease progresses. MV-induced tumors may provide a model for Gram-negative infection and decreased immunologic responsiveness associated with malignancies.

Animals↗
PubMed1983

Immunohistology of malignant rabbit fibroma virus--a comparative study with rabbit myxoma virus.

Malignant rabbit fibroma virus (MV) causes a syndrome that consists of disseminated malignant tumors and immunosuppression complicated by severe Pasteurella multocida infection and death. Tissues from rabbits given MV and rabbit myxoma virus were examined by direct immunofluorescence with the use of antibody against virus antigens. Primary and metastatic tumors caused by MV and rabbit myxoma virus were composed of soft tissue cells containing virus antigens. Skin appendages and epidermis overlying the respective tumors showed scant MV but abundant myxoma virus antigen. Both viruses were present systemically in the reticuloendothelial system. Epithelial cells from the liver, kidney, and lung of myxoma virus-infected rabbits contained virus, whereas in MV tumor-bearing rabbits, these cells were uninvolved. However, nasal mucosal and conjunctival epithelia, the locations of Pasteurella infection, showed squamous metaplasia and contained large amounts of MV and myxoma antigens. By analogy to other respiratory tract pathogens, these epithelial changes were probably etiologically significant for development of pasteurellosis in rabbits bearing virus-induced tumors. Thus by immunopathologic as well as clinical examination, MV produces a syndrome distinct from that seen with rabbit myxoma virus. MV induced severe immunosuppression despite T-lymphocyte hyperplasia in the lymphoid tissues observed. The combination of a systemic virus infection, epithelial alterations that impaired clearance mechanisms, and immunologic dysfunction is likely to contribute to the inability of rabbits given MV to survive their gram-negative infection.

Animals↗
PubMed1983

Malignant rabbit fibroma virus: observations on the culture and histopathologic characteristics of a new virus-induced rabbit tumor.

The clinical, histopathologic, and cultural characteristics of a newly isolated poxvirus, malignant rabbit fibroma virus (MV), were investigated. MV was isolated from tumors induced by an uncloned stock of Shope fibroma virus (SFV). MV, SFV, and rabbit myxoma virus were compared. Similarly to myxoma virus, MV grew to higher titer in vitro than did SFV and produced plaques rather than foci on rabbit kidney cell monolayers. Unlike the local, self-limited fibroblastic proliferations observed in SFV recipients, MV and myxoma caused a fulminant clinical syndrome characterized by malignant histology, metastases, and supervening fatal gram-negative infection with Pasteurella multocida. MV induced a large, protuberant local tumor and discrete metastases histologically resembling myxosarcomas. Draining lymph nodes contained metastases and showed diffuse cortical hyperplasia. Kupffer's cells were prominent in the liver, and macrophages were abundant in the splenic sinusoids. The lungs and trachea were spared, but the conjunctiva and nasal mucosa showed squamous metaplasia and atypia, with overlying Pasteurella infection and underlying tumor. Myxoma virus infection produced similar mucosal changes, but both of these as well as the epidermis overlying the myxomas showed cytoplasmic virus inclusions. Neither the skin nor the epithelial surfaces overlying MV-induced tumors nor the tumors themselves contained virus inclusions. Thus the tumor syndrome caused by MV differed from other known rabbit tumors. Endonuclease restriction digests showed that the MV genome resembled, but was distinct from, rabbit myxoma virus. Opportunistic infection associated with MV-induced disseminated tumor may be an experimental model for the infectious complications that often supervene in host-tumor relationships.

Animals↗
PubMed1983

Immunity to pasteurellosis in compromised rabbits.

Pasteurellosis in the rabbit inoculated with a malignant variant of Shope fibroma virus (SFV-MV) is presented as a model for the study of immunosuppression and immunoprophylaxis in pasteurellosis. The rabbits, before the inoculation, were healthy carriers of Pasteurella multocida. They were intradermally inoculated with SFV-MV, and 3 to 6 days later, a primary tumor appeared at the site of inoculation. By postinoculation day (PID) 7 or 8, the rabbits had snuffles, conjunctivitis, and tumor metastases; death occurred on PID 10 to 14. Rabbits given the nonmalignant Patuxent strain of SFV developed local primary tumors, but not pasteurellosis nor metastases. In SFV-MV-inoculated rabbits, there was decreased responsiveness of spleen lymphocytes to B and T cell mitogens by day 6, and of spleen and peripheral blood lymphocytes by day 10. In addition, SFV-MV antigen was detected (by immunofluorescence) in mononuclear phagocytes in all major organs and in epithelial cells of the conjunctiva and nasal mucosa. Both nasal and conjunctival epithelia showed squamous metaplasia as well. These changes did not appear in SFV-infected rabbits. With SFV-MV-inoculated rabbits, we obtained partial protection against pasteurellosis by immunization with heat-killed P multocida or a cross-protective core lipopolysaccharide mutant of Escherichia coli (J5). Rabbits were immunized before the inoculation with SFV-MV which precipitated "spontaneous" pasteurellosis due to impaired defenses. Rabbits immunized with J5 or P multocida had less severe conjunctivitis and snuffles than nonimmunized controls, indicating that immunization with the J5 mutant may be useful as prophylaxis against pasteurellosis in compromised hosts.

Animals↗
PubMed1983

Immunity to homologous collagens and cartilage proteoglycans in rabbits.

The in vitro incorporation of [3H]-thymidine into spleen cells was used to show that rabbits with experimentally-induced inflammatory arthritis of 1-4 months duration often develop cellular immunity to purified homologous cartilage proteoglycans, type I and III collagens and, less frequently, to type II collagen. Responses to collagens were primarily directed to antigenic determinants exposed on peptides in degraded molecules, whereas responses to proteoglycans were seen with both native and degraded molecules. These in vitro blastogenic responses were shown to be completely dependent on the presence of T lymphocytes in the cultures. This expression of immunity was not demonstrable in rabbits with long duration arthritis (7-12 months) with any of the antigens tested. Some rabbits injected with homologous proteoglycans demonstrated T-cell-dependent cellular, but not humoral, immunity to the injected antigens. In contrast, rabbits injected with heterologous human proteoglycans developed cellular and humoral immunity to the immunizing proteoglycan, but failed to develop cellular immunity to rabbit proteoglycan. Some of these rabbits did, however, produce circulating antibodies which reacted with rabbit proteoglycans. Moreover, antibodies produced by immunizing rabbits with proteoglycans from bovine, chicken and rat cartilages and the hyaluronic acid binding region from rat cartilage proteoglycan often cross-reacted with rabbit proteoglycan, indicating that there are species-common antigenic determinants present in these proteoglycans and in the hyaluronic acid binding region and that these are recognizable in rabbit proteoglycans by rabbit antibodies. This ability to induce selectively cellular or humoral immunity to proteoglycans should be useful for future investigations of the role of such immunity in the pathogenesis of arthritis, although induction of immunity to proteoglycan was not accompanied by any demonstrable synovitis in these rabbits as has been observed in some strains of rats and mice for type II collagen.

Animals↗
PubMed1982

No evidence for post-transcriptional control of albumin and alpha-fetoprotein gene expression in developing rat liver neoplasia.

Rot analysis of hybridization data using highly labeled alpha-fetoprotein (AFP) and albumin (32P)cDNA probes has been used to quantitate AFP and albumin mRNA sequences in RNA preparations from different subcellular fractions of developing rat liver and Morris hepatoma 7777. In addition, size analysis of these mRNA sequences has been carried out by electrophoretic fractionation on agarose gels containing methylmercury hydroxyde and hybridization to radioactive cloned albumin and AFP cDNA probes. In all the tissues examined (fetal, newborn and adult rat liver, and hepatoma 7777) most of the albumin and AFP mRNA sequences were found associated with the polysomes as mature mRNA molecules; less than 2% of these sequences were present in the nuclear or the non polysomal cytoplasmic compartments. The number of AFP mRNA molecules was found to decrease in parallel in all the cellular compartments during rat liver development. In Morris hepatoma 7777 the content of albumin mRNA was considerably decreased in all the cellular fractions as compared to normal liver. These results demonstrate that post-transcriptional control mechanisms leading to an accumulation of non-functional mRNA molecules are not implicated in the changes of expression of albumin and AFP genes during rat liver development and neoplasia.

Animals↗
PubMed1982

Serum regulation of in vitro lymphocyte responses in early experimental syphilis.

Sera from rabbits with early experimental syphilis were tested for their effect on in vitro lymphocyte transformation responses to related specific antigens (sonicated T. pallidum), unrelated specific antigens (sheep erythrocytes), and the T cell mitogen, concanavalin A. Results were compared with responses in preinfection sera and in sera from sham-infected rabbits. Titration experiments in which normal serum was used indicated that optimal lymphocyte responsiveness is obtained with a final serum concentration of 1%. Under these conditions, no differences in concanavalin A stimulation were observed in cultures with syphilitic sera. Responses to sonicated T. pallidum were inhibited, but only by 17 to 25% when compared with the response in preinfection sera. In cultures containing 10% serum, inhibition of lymphocyte proliferation to sonicated T. pallidum antigens was evident with sera from all syphilitic animals from day 10 (55% inhibition) through day 31 (80% inhibition) of infection. Responses to concanavalin A and sheep erythrocytes were significantly inhibited by day 10 sera; only 20% of the sera tested demonstrated substantial nonspecific inhibitory capacity. No differences were evident among sera from any of the sham-infected animals or among the preinfection sera from either group. Pooled serum with high inhibitory activity was fractionated by ammonium sulfate precipitation, DEAE ion exchange chromatography, and Sephadex G-200 gel filtration. Two separate inhibitors were identified: (i) a low-molecular-weight, ammonium sulfate-soluble, nonspecific inhibitory fraction containing albumin and alpha-globulins with the capacity to inhibit both antigen and mitogen responses and (ii) a high-molecular-weight, ammonium sulfate-precipitable, inhibitory fraction containing alpha-globulin and FTA-ABS-reactive immunoglobulin M which affected only the antigen-specific response to sonicated T. pallidum. Immunodiffusion failed to detect immunoglobulin or T. pallidum antigens in either fraction. DEAE-purified immunoglobulin G from immune serum was not inhibitory.

Animals↗
PubMed1982

The relationship between endocytosis of concanavalin A and phytohaemagglutinin receptors and blast transformation, and direct identification of individual rabbit lymphocytes reactive to both mitogens.

Distribution and modulation of rabbit lymphocyte phytohaemagglutinin acceptors and concanavalin A acceptors during activation of rabbit lymphocytes have been examined by electron microscopy. Two types of cell surface acceptors have been tentatively identified, lectin binding acceptors that do not modulate, and receptors that are endocytosed when blast transformation is stimulated. All of the cells have binding acceptors for both lectins. Endocytosis correlates with early blast transformation and serves as an early marker for lymphocyte activation. When examined after 24 h of culture, those cells that undergo blast transformation contain endocytosed lectin receptors, whereas small untransformed cells do not. Capping prior to endocytosis is rarely observed. The mechanism whereby the signal for transformation is maintained after the reaction of lectin with cell surface receptors and transposed to the nucleus is not known. Although we conclude that endocytosis is an early event required for cell activation, it is possible that endocytosis is secondary to other activation events. By evaluation of sequential endocytosis, individual rabbit lymphocytes that endocytose only concanavalin A, only phytohaemagglutinin, both concanavalin A and phytohaemagglutinin, or neither lectin, have been identified.

Animals↗
PubMed1982

Expression of fibronectin and laminin in the rat liver after partial hepatectomy, during carcinogenesis, and in transplantable hepatocellular carcinomas.

The distribution in the F344 rat liver of two extracellular matrix and basement membrane components, fibronectin and laminin, was studied by immunofluorescence. Fibronectin was found diffusely in normal liver lining the sinusoids and in connective tissue surrounding blood vessels and bile ducts; laminin was present predominantly in the basement membranes of blood vessels and bile ducts and was only inconsistently seen lining the sinusoids. After partial hepatectomy (PH), there was a transient decrease of fibronectin in the central and midzone sinusoidal hepatic areas. This decrease was most marked on day 3 after the PH. Carcinogens caused marked changes in the distribution of fibronectin. Large extracellular deposits of fibronectin were seen in areas of oval cell proliferation in livers of rats treated with N-2-fluorenylacetamide (2-FAA) while being fed a choline-deficient diet. In contrast, the nodules that developed in these livers were almost completely devoid of fibronectin staining. Neoplastic nodules produced in rats by cyclic feedings of 2-FAA r by injections of diethylnitrosamine also contained little or no fibronectin. Laminin staining did not change markedly during these treatments, but increased staining was seen associated with the newly formed ductlike structures and oval cells in liver of rats treated with carcinogens. Transplantable hepatomas varied in their fibronectin staining from fibronectin-negative hepatomas to ones with fibronectin staining within or around every tumor cell. Laminin was only found around the vascular structures within the tumors. The presence or absence of fibronectin in hepatomas did not show an obvious correlation to growth rate or metastatic potential of the tumors studied.

2-Acetylaminofluorene↗
PubMed1982

Experimental syphilitic orchitis in rabbits: ultrastructural appearance of Treponema pallidum during phagocytosis and dissolution by macrophages in vivo.

The ultrastructural distribution of Treponema pallidum and the host inflammatory response during experimental testicular infection of rabbits have been examined. During the inductive phase of experimental orchitis both organisms and inflammatory cells, primarily lymphocytes, are coated by amorphous material not seen in other cellular inflammatory reactions. Phagocytosis of organisms by macrophages occurs during the reactive phase. Phagocytic vesicles contain T. pallidum and are frequently lined by amorphous material. T. pallidum do not appear structurally abnormal prior to phagocytosis; destruction of T. pallidum, manifested by swelling and lysis of the organisms, occurs within phagocytic vacuoles. We conclude that removal of organisms during the reactive stage of experimental syphilis is accomplished by phagocytosis and digestion of organisms by macrophages, resulting from a delayed hypersensitivity reaction initiated by specifically sensitized T cells. The presence of amorphous "ground substance" material does not block the inflammatory response and inhibits neither phagocytosis nor digestion by macrophages.

Animals↗
PubMed1982

Surface immunoglobulin on rabbit lymphoid cells. VII. Binding of exogenous Ig by neonatal lymphocytes and ability of aggregated Ig in neonatal sera to bind to adult cells.

The expression of endogenous and exogenous surface immunoglobulin (sIg) on the surface peripheral blood lymphocytes from adult and neonatal rabbits has been examined. Endogenous and exogenous sIg on rabbit lymphocytes differ in ultrastructural appearance and modulation characteristics. At 0 degree C immunoferritin-labeled endogenous sIg appears as small flat patches on the surface membrane whereas exogenous Ig appears as large ramose clumps. Immunoferritin-labeled endogenous Ig undergoes endocytosis at 37 degrees C, whereas exogenous Ig is shed or sloughed from the cell membrane within 60-90 min at 37 degrees C. Ig from serum or plasma which has been frozen and thawed shows a high degree of binding to peripheral blood lymphocytes, whereas Ig from fresh serum or plasma shows little or no binding. Aggregated Ig from both adult and newborn sera are able to bind to lymphocyte Fc receptors and both adult and neonatal PBLs are able to bind exogenous aggregated Ig.

Aging↗
PubMed1981

Autoradiography of "oval cells" appearing rapidly in the livers of rats fed N-2-fluorenylacetamide in a choline devoid diet.

Autoradiographic analysis of liver sections from rats fed the hepatocarcinogen N-2-fluorenylacetamide (FAA) in a choline devoid (CD) diet suggests that proliferating small "oval" cells arise from a few small portally-situated cells, and spread rapidly across the entire liver lobule. Small cells with detectable grains are first located where liver plates meet the portal areas. This cell type gradually increases in number over a 10-12 day period, then proliferates rapidly. After 28 days, microscopic nodules consisting of heavily labeled large eosinophilic cells appear, whereas residual hepatocytes are not labeled. Combined immunofluorescent and autoradiographic labeling studies reveal that many of the small cells contain AFP; approximately half of the alpha-fetoprotein-containing cells are labeled with [3H]thymidine (dT). Feeding CD-FAA diets to rats with hepatocytes prelabeled with [3H]dT after 70% hepatectomy 7 weeks earlier provides data which suggest that small "oval" cells do not arise from prelabeled hepatocytes but, instead, infiltrate the prelabeled hepatocytes during the diet induced proliferative phase. We conclude that "oval" cells arise from a small number of portal cells, not from hepatocytes. Exact identification of the oval cell precursor is not possible, but it could be a "stem" cell. Although hepatocyte-like properties are found in small cells (e.g., albumin staining), there is no evidence that they differentiate into normally functioning hepatocytes.

2-Acetylaminofluorene↗
PubMed1981

Studies on group B beta-hemolytic Streptococcus. I. Isolation and partial characterization of an extracellular toxin.

To initiate an investigation into the biochemistry and mechanism of group B beta-hemolytic Streptococcus virulence, bacterial cultures grown in suspension were centrifuged, and the bacteria and media were subjected to extensive fractionation. Each fraction was assayed for physiologic activity by repeated intravenous infusion into adult unanesthetized sheep. Pulmonary artery pressure, arterial PO2, and rectal temperature were monitored. The media fraction, but not the bacteria, contained a component (molecular weight, 2 x 10(6)) composed of 845 carbohydrate and 16% protein with physiological activity. Two mg quantities, when infused, caused the pulmonary artery pressure to increase 100%, PO2 to decrease by 20% and chills and fever. The active component could be degraded by hot phenol-water extraction into a pure polysaccharide (molecular weight, 200,000). This lower molecular weight polysaccharide retained the identical physiologic properties when infused in the sheep. The degraded component precipitated with group B-specific antiserum. This study demonstrates that, in the sheep, a pure polysaccharide is the physiologically active part of a high-molecular-weight toxin synthesized by group B beta-hemolytic Streptococcus type III and that this component has a different carbohydrate composition from the group B capsular antigen.

Animals↗
PubMed1981

Surface immunoglobulin-bearing rabbit lymphocytes express both VH and L chain allotypic determinants.

The cell surface distributions of a locus and b lucus rabbit immunoglobulin allotypes have been examined simultaneously, using immunoelectronmicroscopic techniques. Most rabbit lymphocytes that bear surface immunoglobulin express both a and b markers. This is true of lymphocytes from blood, spleen, and lymph node of normal and immunized rabbits. A preponderance of cells bearing VH markers (a locus) but not L chain markers (b locus) was not observed.

Animals↗