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Biomedical subjects

N C Pedersen

Publications and source records attributed to N C Pedersen.

At least 163 records · Page 9Linked to original sources

Biological behavior of tumors and associated retroviremia in cats inoculated with Snyder-Theilen fibrosarcoma virus and the phenomenon of tumor recurrence after primary regression.

The fate of tumors and associated retroviremia was studied in 111 cats infected with the Snyder-Theilen strain of feline sarcoma virus (FeSV). Tumors appeared at the site of inoculation within 7 to 10 days. A retroviremia, due mainly to the associated feline leukemia virus helper virus (FeLV-helper), developed at the same time as tumors. Of the cats, 44 developed progressively growing tumors and therefore had to be killed, and 67 developed tumors that regressed. There was a strong correlation between the persistence of the accompanying retroviremia and the growth of the tumors. The 44 cats with progressively growing fibrosarcomas remained retroviremic until death. Conversely, 53 of the 67 cats with solitary, regressing tumors were only transiently retroviremic. Tumor regression in these cats paralleled the disappearance of retrovirus from the blood. The fate of tumors and retroviremia was not always the same, however. Twelve cats remained persistently retroviremic after all signs of gross tumors disappeared. Two other kittens became nonviremic within 20 days after inoculation, yet tumors continued to grow and even metastasize for another 3 to 5 weeks before regressing. Fibrosarcomas recurred 3 weeks to 8 months later in 8 of 12 persistently retroviremic cats with regressed tumors. Although the blood and bone marrow from these cats contained predominantly FeLV-helper, tumor cells yielded both FeSV and FeLV-helper. Of 53 animals, 3 developed recurrent fibrosarcomas 5 weeks to 8 months after all signs of tumors and retroviremia had disappeared. Cells cultured from these tumors appeared initially like normal fibroblasts and were virus nonproducers. After one to three passages in culture, however, cells became malignantly transformed and replicated both FeSV and FeLV-helper. Cultures of the bone marrow from these and other nonviremic cats with regressed tumors yielded only FeLV-helper.

Animals↗

Pathogenicity studies of feline coronavirus isolates 79-1146 and 79-1683.

Two feline coronavirus isolates were characterized by their disease-causing potential in cats. The 79-1683 feline coronavirus isolate caused an inapparent-to-mild enteritis when given oronasally to specific-pathogen-free kittens and was not a cause of feline infectious peritonitis (FIP). Target tissues for the virus were the mature apical epithelium of the small intestine, mesenteric lymph nodes, tonsils, thymus, and (to a lesser extent) the lungs. Inoculated kittens shed high numbers of virus in their feces for 14 to 17 days, but remained infectious to susceptible kittens for longer periods of time, as evidenced by contact-exposure studies. Because the 79-1683 isolate induced only enteritis, it was designated feline enteric coronavirus (FECV) 79-1683. The 79-1146 feline coronavirus isolate induced effusive abdominal FIP in specific-pathogen-free kittens after oronasal and intraperitoneal inoculation. Clinical signs of disease appeared within 12 to 14 days in almost all inoculated kittens. Because this isolate caused FIP, it was designated FIP virus (FIPV) 79-1146. Cross-protective immunity was not induced by the various coronavirus infections. Kittens preimmunized with the UCD strain of FECV (FECV-UCD) or with FECV-79-1683 were not immune to infection with FIPV-79-1146. Likewise, kittens previously inoculated with FECV-79-1683 were not immune to infection with FIPV-UCD1. In fact, preexisting heterologous FECV-79-1683 immunity often accelerated and enhanced the severity of disease caused by inoculation with FIPV-UCD1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Monoclonal antibodies to three epitopic regions of feline leukemia virus p27 and their use in enzyme-linked immunosorbent assay of p27.

Three different monoclonal antibodies were developed against the major core protein (p27) of feline leukemia virus (FeLV). Each antibody was directed against a different epitope of the species-specific portion of FeLV-p27. The 3 antibodies reacted with 5 different isolates of FeLV but not with 7 other retroviruses (MuLV (Rauscher), MuLV (AKR), MPMV, MMTV, SMRV, BAEV, RD 114). These monoclonal antibodies could readily be adapted to an enzyme-linked immunosorbent assay (ELISA) for the specific measurement of FeLV-p27. When compared in an ELISA with conventional reagents, the battery of monoclonal antibodies proved to be as sensitive as conventional polyclonal antibodies.

Animals↗

Active immunization with feline leukemia virus envelope glycoprotein suppresses growth of virus-induced feline sarcoma.

The efficiency was examined of immunization with feline leukemia virus glycoprotein complexes (gp85 rosettes) to protect cats against tumors induced by feline sarcoma virus (FeSV). The glycoprotein was isolated from feline leukemia virus (FeLV). Young cats were vaccinated with the purified viral glycoprotein and challenged with FeSV (FeLV). FeLV gp85 antibody levels were measured by enzyme-linked immunosorbent assay and tumor volumes were determined. In immunized animals tumor development was reduced. Gp85 antibody levels before challenge were correlated inversely with tumor size (r2 = 0.79). This method appears to be suitable for fast and efficient testing of future FeLV vaccines.

Animals↗

Nocardia asteroides recovery from a dog with steroid- and antibiotic-unresponsive idiopathic polyarthritis.

This report describes a fatal case of idiopathic polyarthritis in a dog that was partially responsive to vigorous immunosuppressive treatment. Synovial fluids were cultured for L-forms at the following stages of disease: (i) acute arthritic relapse, (ii) incomplete remission, and (iii) death. Nocardia asteroides UCD 1-581 was recovered from the L-form broth culture of the specimen taken during acute relapse, 5 weeks after inoculation, but not at any other stage of disease. Numerous conventional microbiological cultures were unproductive during all phases. Changes occurring in L-form plates included the formation of large irregular mineral deposits and many transferable bodies resembling pseudocolonies. Microscopic examination revealed the presence of many intracellular golden-brown granules and acid-fast bodies in macrophages of the lung and bronchial lymph node tissues. The granules are believed to be the variants embedded in calcium deposits similar to those which developed in the L-form cultures in vitro. Fluorescence of these acid-fast bodies with antibody specific for superoxide dismutase of N. asteroides GUH-2 and labeled anti-immunoglobulin G established their relationship to the isolate. The unrelenting course of disease and the persistence of N. asteroides as an L-form in this animal despite vigorous immunosuppression suggest that this organism plays a direct role in the etiology of this disease.

Adrenal Cortex Hormones↗

Attempted immunization of cats against feline infectious peritonitis, using avirulent live virus or sublethal amounts of virulent virus.

Kittens vaccinated with an avirulent biotype of the Black strain of feline infectious peritonitis virus (FIPV; given oronasally) developed both indirect fluorescent and virus-neutralizing antibodies, but were not protected against oronasal challenge exposure with virulent virus. In fact, kittens vaccinated with avirulent virus were more readily infected than were nonvaccinated cats. A proportion of kittens could be immunized to FIPV by giving sublethal amounts of virulent virus. This technique, however, was too inconsistent and hazardous to have clinical relevance. The results of these studies indicated that humoral immunity was not protective in FIPV infection. There was no correlation between fluorescent and virus-neutralizing antibodies and either disease or immunity. Immune serum from FIPV-resistant cats failed to passively protect susceptible animals against virulent virus given intraperitoneally or oronasally, and as expected, actually sensitized them to infection. It was concluded that cell-mediated immunity was probably responsible for protection.

Animals↗

Course of feline leukemia virus infection and its detection by enzyme-linked immunosorbent assay and monoclonal antibodies.

Monoclonal antibodies specific for 3 distinct epitopes of the species-specific determinants of feline leukemia virus (FeLV) p27 were used in an enzyme-linked immunosorbent assay (ELISA) for measurement of serum p27 in cats infected with FeLV. Group-specific antigen (GSA) of FeLV in peripheral blood leukocytes was also determined by an immunofluorescence assay. Antibodies to FeLV and the feline oncornavirus-associated cell membrane antigen (FOCMA) were also measured. Thirty-six cats were surveyed and assigned to 4 categories. Five developed persistent viremia (category 1), characterized by continuous expression of p27, GSA, and low antibody titers to FeLV and FOCMA. Eleven cats with transient viremia (category 2) and 13 cats that were never detectably viremic (category 3), as judged by absence of GSA and p27, developed increased antibody titers to FeLV and FOCMA. Seven cats were never viremic, as judged by the GSA in the peripheral blood leukocytes, but still had detectable serum p27 (category 4). Most category 4 cats developed high antibody titers against FOCMA and/or FeLV. Of 307 field cats examined, 7% of the healthy cats and 10% of the sick cats could be assigned to category 4. However, this difference was not significant (P greater than or equal to 0.05). Of 26 cats with neoplasms 2 (1 of 12 with lymphosarcoma) could be classified as category 4. Because virus could be isolated from 2 category 4 cats, they were considered immune carriers.

Animals↗

Comparison of hemagglutination and competitive enzyme-linked immunosorbent assay procedures for detecting canine parvovirus in feces.

A competitive enzyme-linked immunosorbent assay (ELISA) for detection of canine parvovirus (CPV) antigen in fecal samples was developed. Fecal samples were tested by ELISA and a direct hemagglutination assay, and the results compared. The tests gave the same results in 83% and 88% of the fecal samples, depending on whether the samples were treated with chloroform. The discrepancies were due to the fact that each test detected virus in certain fecal samples that was not detected by the other. The use of a monoclonal anti-CPV conjugate resulted in a highly specific test. The performance of the ELISA as a competitive assay also increased the reproducibility and sensitivity over that which could be obtained from a classic sandwich-type procedure.

Animals↗

Antigenic relationships among homologous structural polypeptides of porcine, feline, and canine coronaviruses.

Transmissible gastroenteritis virus of swine (TGEV), feline infectious peritonitis virus (FIPV), and canine coronavirus were studied with respect to their serological cross-reactivity in homologous and heterologous virus neutralization, immune precipitation of radiolabeled TGEV, electroblotting, and enzyme-linked immunosorbent assay using individual virion polypeptides prepared by polyacrylamide gel electrophoresis. TGEV was neutralized by feline anti-FIPV serum, and the reaction was potentiated by complement; heterologous neutralization involved antibody reacting with the peplomer protein (P), the envelope protein (E), and cellular (glycolipid) components incorporated into the TGEV membrane. Electrophoretic analysis of immune precipitates containing [35S]methionine-labeled disrupted TGEV and feline anti-FIPV antibody confirmed the reaction with the P and E polypeptides and showed the nucleocapsid protein (N) in addition. Electroblotting, followed by incubation with antibody, 125I-labeled protein A, and fluorography, disclosed cross-reactions between the three viruses at the N and E levels and revealed differences in the apparent molecular weights of the latter. Enzyme immunoassays performed with standard amounts of immobilized P, N, and E polypeptides of the three viruses showed recognition of the antigens by homologous and heterologous antibody to comparable degrees. These results indicate a close antigenic relationship between TGEV, FIPV, and canine coronavirus due to common determinants on the three major virion proteins. The taxonomic implications of these findings are discussed.

Animals↗

Recovery of microorganisms from synovial and pleural fluids of animals using hyperosmolar media.

L-phase (CWD) broth and plate media were used in parallel with conventional microbiological media during a 3-year period for culturing synovial and pleural fluids of animals. Two kinds of recoveries were obtained where parallel conventional methods were negative: (1) parent or normal bacteria, in very low numbers; and (2) Type B CWD variants in equally low numbers. Organisms in group 1 were: Streptococcus zooepidemicus from horses (2x); beta-hemolytic streptococci, Lancefield Gp. G (2x); Staphylococcus aureus; Actinobacillus, and Actinomyces viscosus. Group 2 consisted of Bacteroides sp., Propionibacterium acnes, and three "Nocardia-like" sp. Catalase + Actinomyces was not recovered equally well on CWD plates as on conventional media with fluids obtained during ampicillin treatment. This occurred in spite of the fact that the CWD media was shown to support growth and reversion of laboratory induced L-phase variants of Nocardia caviae and N. asteroides, and had facilitated recovery of a Bacteroides L-phase variant from a pleural fluid. The nature of this fault in the media is under investigation in this laboratory.

Actinomyces↗

Infection studies in kittens, using feline infectious peritonitis virus propagated in cell culture.

The propagation of feline infectious peritonitis virus (NW1-FIPV strain) in cell culture is described. Tissue culture-propagated virus was used to inoculate specific-pathogen-free kittens intraperitoneally, intratracheally, or orally. Intraperitoneal inoculation caused seroconversion and effusive peritonitis in 100% of the kittens. Intratracheal inoculation produced disease in 60% of the kittens, and oral inoculation in only 20%. Seroconversions without production of disease occurred in 10% of the kittens inoculated by either the intratracheal or the oral route. The remainder of the kittens inoculated by the intratracheal (30%) and oral (70%) routes did not develop serum antibodies or disease.

Administration, Oral↗

An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis.

An enteric coronavirus that is antigenically closely related to feline infectious peritonitis virus (FIPV) is ubiquitous in the cat population. This virus has been designated feline enteric coronavirus to differentiate it from FIPV. The virus is shed in the feces by many seropositive cats; in catteries it is a cause of inapparent to mildly severe enteritis in kittens 6 to 12 weeks of age. The virus may produce a more severe enteritis in young specific-pathogen-free kittens. Feline enteric coronavirus selectively infects the apical columnar epithelium of the intestinal villi, from the caudal part of the duodenum to the cecum. In severe infections, there are sloughing of the tips of the villi and villous atrophy. Many cats recovering from the disease remain carriers of the virus. Recovered cats, observed for 3 to 24 months, remained healthy and did not develop peritonitis, pleuritis, or granulomatous disease. The relationship of feline enteric coronavirus and FIPV was studied. Although the viruses were antigenically similar, they were distinctly different in their pathogenicities. The enteric coronavirus did not cause feline infectious peritonitis in coronavirus antibody-negative cats inoculated orally or intraperitoneally nor in coronavirus antibody-positive cats inoculated intraperitoneally or intratracheally. Serologic tests, using FIPV, canine coronavirus, and transmissible gastroenteritis virus of swine as substrate antigens in fluorescent antibody procedures may not accurately identify FIPV infection. These tests do not appear to distinguish between FIPV and this feline enteric coronavirus.

Animals↗

Feline chronic progressive polyarthritis.

Twenty cats with a chronic progressive polyarthritis were studied. The disorder occurred exclusively in male cats, and all but six of the cats were between 1.5 and 5.0 years of age. There were two forms of the disease as determined by radiographic changes: joint instability and deformity, and clinical course. The most prevalent form of the disease was characterized by osteopenia and periosteal new bone formation surrounding affected joints. Marginal periarticular erosions and collapse of the joint spaces with fibrous ankylosis occurred with time, but joint instability and deformities were not seen. The second form of the disease was characterized by severe subchondral marginal erosions, joint instability, and deformities. The periosteal proliferative form resembled Reiter's arthritis of man, and the deforming type resembled human rheumatoid arthritis. The disease began as tenosynovitis and synovitis, with subsequent changes in the articular cartilage and periosteal bone. Histopathologic changes in these cats were similar to those occurring in both chronic Reiter's and rheumatoid arthritis of man. Chronic progressive polyarthritis of cats was not caused by identifiable bacteria or mycoplasma, but was etiologically linked to feline leukemia virus (FeLV) and feline syncytia-forming virus (FeSFV) infections. The FeSFV was isolated from the blood or was detected by a serologic test in all of the cats with the disease, whereas FeLV was isolated or identified by immunofluorescence technique in 60% of the cats. The arthritis could not be reproduced by inoculation of cell-free cynovial tissue from diseased cats or with tissue culture fluid containing FeSFV and FeLV isolates. It was postulated that arthritis was an uncommon manifestation of FeSFV infection that occurred in predisposed male cats. Feline leukemia virus may not have been directly involved in the disease, but may have acted in some way to potentiate the pathogenic effects of FeSFV.

Animals↗

The demonstration of antibody specificity by a new technique. The gel electrophoresis-derived enzyme-linked immunosorbent assay (GEDELISA) and its application to antibodies specific for feline leukemia virus.

By combining the high resolution of sodium dodecylsulfate polyacrylamide gel electrophoresis with the sensitivity of enzyme-linked immunosorbent assay (ELISA) antibodies specific for different feline leukemia virus components are characterized. Based on the same principle, Concanavalin A binding sites of FeLV components are also detected.

Antibodies, Viral↗

Role of regional and distant lymph nodes in rejection of feline sarcoma virus-induced tumors in sheep.

The immune response of regional and distant lymph nodes was compared relative to rejection of feline sarcoma virus (FeSV)-induced tumors in sheep. Following injection of FeSV-transformed allogeneic or autochthonous fibroblasts into the lower leg, small tumors developed at the site of inoculation and subsequently regressed. Efferent lymph from the regional popliteal nodes and distant nodes in the same host was collected for periods up to 40 days after tumor cell inoculation. The cell response in the efferent lymph of the stimulated node was the same regardless of whether inoculum consisted of autochthonous or allogeneic FeSV-transformed sheep cells. There was a rapid rise in total lymphocytes leaving the regional node, beginning at 3 days and peaking at 6--8 days post inoculation. On days 6--8 post inoculation, lymphoblasts appeared in regional lymph ranging from 25 to 40% of the total cell output. The cell population in lymph from distant (nonstimulated) nodes, however, remained morphologically normal throughout the response. Lymphocytes cytotoxic to the injected FeSV-transformed cells appeared in efferent lymph from the regional node within 5 days post inoculation and in lymph from distant nonstimulated nodes several days later. Cytotoxic lymphocytic cells had no "killing" effect against the corresponding nontransformed cells if the inoculum was autochthonous in origin; however, they did have such an effect when corresponding nontransformed cells were allogeneic. The cytotoxicity of lymph cells varied according to the type of cells in the lymph. With the use of the growth inhibition assay, it was possible to demonstrate that lymph cell populations high in lymphoblasts "killed" all target cells in 24 hours, whereas populations of lymph cells comprised mainly of small lymphocytes took up to 2--3 days to "kill" the target cells. Complement-dependent antibody first appeared in lymph from the stimulated popliteal node at 8 days post inoculation and at 12 days post inoculation in blood sera and lymph from distant nodes.

Animals↗