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Biomedical subjects

N C Pedersen

Publications and source records attributed to N C Pedersen.

At least 181 records · Page 10Linked to original sources

Safety and efficacy studies of live- and killed-feline leukemia virus vaccines.

The safety and the efficacy of several feline leukemia virus (FeLV) vaccines for 16-week-old kittens were determined. Vaccines were derived from an FL74 lymphoblastoid cell line that has been in continuous tissue culture passage for about 4 years. The vaccines were made from living virus, formaldehyde-inactivated whole FL74 cells, and formaldehyde-inactivated whole virus. The efficacy of each produced vaccine was determined by challenge exposure of vaccinated cats with virulent FeLV. The two formaldehyde-inactivated vaccines were found to be safe for use in kittens. Neither vaccine produce a significant feline oncornavirus-associated cell membrane antigen or virus-neutralizing antibody response, nor did they prevent infection with virulent FeLV. The inactivated whole-virus vaccine, however, did substantially decrease the proportion of kittens infected with virulent FeLV that became persistently viremic. In contrast, the whole FL74 cell vaccine did not reduce the number of infected kittens that became persistently viremic. The live-virus vaccine was found to be both safe and efficacious. About a half of the kittens vaccinated with live virus had transient bone marrow infection that lasted from 2 to 4 weeks. Viral antigen was not detected in peripheral blood, and infective virus was not shed in saliva, urine, or feces during the period that the vaccinal virus could be recovered from the bone marrow. In addition, there was no horizontal spread of vaccinal virus from vaccinated to non-vaccinated cagemates. Within several weeks, vaccinated kittens demonstrated no clinical or hematologic abnormalities and had high serum levels of feline oncornavirus-associated cell membrane antigen and virus-neutralizing antibody. Kittens vaccinated with living FeLV were resistant to infection with virulent virus.

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Rabies vaccine virus infection in three dogs.

Ascending paralysis developed in 3 dogs, 12 to 14 days following inoculation with a modified live virus, chicken embryo origin, low egg passage, Flury strain rabies vaccine. The paralysis began in the inoculated limb but rapidly involved both hindlimbs. Partial paresis of the forelimbs was seen several days following the hindlimb paralysis in all 3 dogs, and in 1 of these dogs the infection ascended rapidly to the brain as well. Two of the dogs recovered within 1 and 2 months, respectively, but the 3rd dog died within 5 days of the onset of paralytic signs. The fatal case was complicated by naturally acquired coincidental distemper. Serologic studies in 2 dogs and virus isolation from the 3rd dog indicated that rabies virus was the cause of the paralysis in 2 of the dogs and contributed to the disease syndrome in the 3rd dog. Virus could not be isolated from the saliva of CSF of the 2 surviving dogs. The virus isolated in the fatal case appeared to have some of the characteristics of the vaccine virus, as determined by its behavior in mice, cell culture, and embryonating chicken eggs and by its failure to produce Negri bodies in the brain of the infected dog.

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Antigenic relationship of the feline infectious peritonitis virus to coronaviruses of other species.

Utilizing the direct and indirect fluorescent antibody procedure, the antigenic relationship of the feline infectious peritonitis virus (FIPV) to 7 other human and animal coronaviruses was studied. FIPV was found to be closely related to transmissible gastroenteritis virus (TGEV) of swine. Transmissible gastroenteritis virus and FIPV were in turn antigenically related to human coronavirus 229E (HCV-229E) and canine coronavirus (CCV). An interesting finding in the study was that the 8 coronaviruses selected for this study fell into one of two antigenically distinct groups. Viruses in each group were antigenically related to each other to varying degrees, but were antigenically unrelated to coronaviruses of the second group. The first antigenically related group was comprised of mouse hepatitis virus, type 3 (MHV-3), hemeagglutinating encephalomyelitis virus 67N (HEV-67N) of swine, calf diarrhea coronavirus (CDCV), and human coronavirus 0C43 (HCV-OC43). The second antigenically related group was comprised of FIPV, TGEV, HCV-229E and CCV.

Antigens, Viral↗

Noninfectious canine arthritis: the inflammatory, nonerosive arthritides.

Noninfectious, nonerosive arthritis was seen as an important manifestation of a number of chronic systemic diseases of the dog. Sixty-three dogs with this type of arthritis were seen at the Veterinary Medical Teaching Hospital during an 18-month period between 1973 and 1975. Of these dogs, 29 had systemic lupus erythematosus, 15 had arthritis in association with some chronic infectious disease process, and 19 had a similar type of arthritis, but without serologic evidence of systemic lupus erythematosus or any chronic infectious disease process.

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Noninfectious canine arthritis: rheumatoid arthritis.

Chronic unremitting, generally symmetric, erosive polyarthritis was studied in 8 dogs. The disease had clinical, serologic, radiographic, and pathologic changes similar to those of rheumatoid arthritis of man. The condition occurred mainly in smaller breeds of dogs, with time of onset from 8 months to 8 years of age, Characteristic radiographic changes were seen in the joints several weeks to several months after the appearance of the initial lameness. Synovial fluid contained an increased number of neutrophils, and synovial fluid and synovial tissues were sterile for anaerobic and aerobic bacteria, mycoplasma, chlamydia, and viruses. Corticosteroids were therapeutically ineffective in all of the cases; however, corticosteroids, cyclophosphamide, and azathioprine were effective when used in combination in several dogs.

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Morphologic and physical characteristics of feline infectious peritonitis virus and its growth in autochthonous peritoneal cell cultures.

Characteristic viral-type particles were seen in liver of kittens experimentally infected with the feline infectious peritonitis (FIP) agent. The particles were from 70 to 75 nm in diameter, with a central doughnut-shaped nucleoid 50 to 55 nm in diameter; numerous spikelike projections extended from their envelopes. Similar particles were seen by electron microscopy in peritoneal cell cultures derived from the peritoneal exudate of experimentally infected kittens, and viral antigens were identified in these cells by immunofluorescence. Cells and supernatant fluids from cultures containing these particles produced FIP when injected into the peritoneal cavity of kittens. The FIP agent is heat sensitive, ether labile, and relatively phenol resistant and is inactivated within 24 hours at room temperature. The FIP agent is inactivated by recommended viricidal concentrations of chlorhexidine and benzlkonium chloride.

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Serologic studies of naturally occurring feline infectious peritonitis.

Serum antibodies to the feline infectious peritonitis (FIP) virus were measured in cats, using an indirect fluorescent antibody procedure. Antibody titers of 1:400 to 1:25,600 were seen in cats with both effusive and noneffusive forms of FIP. About 87% of the normal cats in FIP problem catteries and 20% of the cats in the Davis, Ca, area also had antibody titers to the FIP virus, ranging from 1:25 to 1:400. Although the infection rate is high among cats, relatively few of the cats infected with the FIP virus ever develop clinically apparent FIP.

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The response of the lymphoid system to renal allografts in sheep.

The immunological events which occur in lymph nodes situation regional to renal allografts have been studied by collecting lymph from these nodes and monitoring the changes in its cellular and humoral antibody content. Simultaneously, reactions occurring in the renal allograft and in lymph nodes distant to the graft were also monitored in the lymph from these organs throughout thelife of the graft. Large basophilic lymphoid cells appeared first in lymph from the renal allograft at around 48 hr postgrafting, whereas these cells did not appear in the lymph from the regional node until 80-100 hr after the graft was installed. Lymphoid blast cells were not seen inany significant numbers in lumph from nodes situated at a distance from the graft. The first detectable antibody was produced by the regional lymph node between 110 and 175 hr postgrafting, andin other undetermined sites within the next 80 hr. Antibody was not synthesized in any detectable amounts by the graft or by lymph nodes situated at a distance from the graft. The antibody which was present in the lymph from the regional node was produced primarily by fixed cells which remained in the node, and very little antibody was produced by the lymphoid cells which migrated from the node in efferent lymph. The cells in the lymph from the renal allograft produced only small amounts of immunoglobulin. Cells present in lymph from the renal allograft and in lymph from the regional lymph node actively synthesized and secreted significant amounts of nonimmunoglobulin proteins which were separated on Sephadex G-200 columns into peaks which coincided with 19S, 7S, and 4S proteins. The identities and biological activities of these proteins have not yet been determined.

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The role of humoral antibody in the rejection of primary renal allografts in sheep.

Antibody which had cytotoxic and agglutinating activity against donor lymphocytes appeared in the blood stream of primary renal allograft recipients usually within 48 h of the graft being finally rejected. Appearance of the antibody See PDF for Structure in the blood was associated with severe alterations in vascular permeability and this led to increases in the numbers of red cells and in the protein content of the lymph coming from the allograft. It was possible to elute cytotoxic and agglutinating antibody from renal allograft tissue, showing that this type of antibody was bound to graft antigens during the rejection process. The transfusion of whole serum or serum globulins obtained from sheep that had previously rejected allografts led to the destruction of recently installed renal grafts and the histological changes produced in these grafts and the alterations in the composition of the lymph coming from them were similar to those seen in the terminal stages of primary rejection. These findings have led us to the conclusion that in the sheep, at least the terminal stage of primary renal allograft rejection is mediated by humoral antibody.

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The role of the lymphatic system in the rejection of homografts: a study of lymph from renal transplants.

The rejection of renal homografts has been studied in sheep by transplanting kidneys into the neck and preserving the renal lymphatic drainage intact. Chronic fistulae were established in the transplanted renal lymphatics and lymph collected throughout the life of the graft. The changes that occurred in homografts during the process of rejection were reflected in changes in the lymph. Large numbers of basophilic, blast, lymphoid cells appeared in the lymph, and lymph production in the grafted kidney increased 20-50 fold. Over a period of about 10 days, up to 60 g wet weight of lymphoid cells and up to 10 liters of lymph were collected from the graft. Within 24 hr of grafting, the host cells present in the renal lymph had become sensitized to the graft and transformed into blast cells when cultivated in Millipore chambers in vitro. When the cells leaving the graft during the first 18-48 hr were injected into distant nonstimulated lymph nodes of the host sheep, they evoked significant cellular and antibody responses in the nodes. Within the graft, the main pathological changes were found in the vascular endothelium and many of the peritubular capillaries become plugged with emboli comprised of blast cells. There was extensive infiltration of the renal parenchyma with lymphoid cells and evidence of their transformation and proliferation within the renal blood capillaries. When all the lymph and cells leaving the homograft were diverted from the body, there was a greatly decreased reaction in the regional prescapular lymph node, and no reaction in lymph nodes distant from the graft. In these circumstances, the survival of the graft was not prolonged, and it was rejected without involvement of the lymph nodes of the host. Humoral antibody was produced in the lymph node regional to the homograft within 48-60 hr of grafting. Antibody was not detected in the blood or in the renal lymph until near to the time the graft was rejected. It was thought that this was due to the binding of antibody by the kidney graft tissue. We conclude that all the events which lead to the recognition and rejection of renal homografts can occur centrally within the graft itself.

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