Search PubMed⌕ Search

Biomedical subjects

N C Pedersen

Publications and source records attributed to N C Pedersen.

At least 91 records · Page 5Linked to original sources
PubMed1993

Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac.

To identify viral determinants of simian immunodeficiency virus (SIV) virulence, two pairs of reciprocal recombinants constructed from a pathogenic (SIVmac239) and a nonpathogenic (SIVmac1A11) molecular clone of SIV were tested in rhesus macaques. A large 6.2-kb fragment containing gag, pol, env, and the regulatory genes from each of the cloned (parental) viruses was exchanged to produce one pair of recombinant viruses (designated SIVmac1A11/239gag-env/1A11 and SIVmac239/1A11gag-env/239 to indicate the genetic origins of the 5'/internal/3' regions, respectively, of the virus). A smaller 1.4-kb fragment containing the external env domain of each of the parental viruses was exchanged to create the second pair (SIVmac1A11/239env/1A11 and SIVmac239/1A11env/239) of recombinant viruses. Each of the two parental and four recombinant viruses was inoculated intravenously into four rhesus macaques, and all 24 animals were viremic by 4 weeks postinoculation (p.i.). Virus could not be isolated from peripheral blood mononuclear cells (PBMC) of any animals infected with SIVmac1A11 after 6 weeks p.i. but was consistently isolated from all macaques inoculated with SIVmac239 for 92 weeks p.i. Virus isolation was variable from animals infected with recombinant viruses; SIVmac1A11/239gag-env/1A11 and SIVmac239/1A11env/239 were isolated most frequently. Animals inoculated with SIVmac239 had 10 to 100 times more virus-infected PBMC than those infected with recombinant viruses. Three animals infected with SIVmac239 died with simian AIDS (SAIDS) during the 2-year observation period after inoculation, and the fourth SIVmac239-infected animal had clinical signs of SAIDS. Two animals infected with recombinant viruses died with SAIDS; one was infected with SIVmac239/1A11gag-env/239, and the other was infected with SIVmac1A11/239gag-env/1A11. The remaining 18 macaques remained healthy by 2 years p.i., and 13 were aviremic. One year after inoculation, peripheral lymph nodes of some of these healthy, aviremic animals harbored infected cells. All animals seroconverted within the first few weeks of infection, and the magnitude of antibody response to SIV was proportional to the levels and duration of viremia. Virus-suppressive PBMC were detected within 2 to 4 weeks p.i. in all animals but tended to decline as viremia disappeared. There was no association of levels of cell-mediated virus-suppressive activity and either virus load or disease progression. Taken together, these results indicate that differences in more than one region of the viral genome are responsible for the lack of virulence of SIVmac1A11.

Animals↗
PubMed1993

Delayed seroconversion following naturally acquired caprine arthritis-encephalitis virus infection in goats.

One hundred eight milking goats from a dairy that had been using a modified caprine arthritis-encephalitis virus (CAEV) eradication program were tested for CAEV antibodies by serologic methods and for proviral CAEV DNA by use of polymerase chain reaction (PCR) technology. All goats were free of clinical symptoms of CAEV infection. Twenty-seven of the 108 goats were considered seropositive, on the basis of ELISA results. Proviral CAEV DNA was detected, using PCR techniques, in mononuclear leukocytes in blood samples obtained from 25 of the these 27 seropositive goats. Twenty of the 81 seronegative goats also had positive PCR test results. Ten of these goats seroconverted by 8 months later, and virus was readily isolated from mononuclear leukocytes in venous blood samples after the goats had seroconverted. Virus was also isolated from mononuclear leukocytes in blood samples collected from 4 of 11 goats that were seronegative, but had positive PCR test results. These results indicated that seroconversion can be delayed for many months following natural infection with CAEV. Delayed seroconversion appears to be a feature of CAEV infection, which may have direct implications for CAEV eradication programs and epidemiologic studies that rely on serologic methods to detect infected goats.

Animals↗
PubMed1993

Evaluation of cofactor effect of feline syncytium-forming virus on feline immunodeficiency virus infection.

Although feline immunodeficiency virus (FIV) and the unrelated retrovirus feline leukemia virus (FeLV) are associated with acquired immune deficiency in cats, experimental and field evidence indicates that coinfection with both viruses may lead to more serious disease syndrome. A third feline retrovirus, feline syncytium-forming virus (FeSFV), which is far more prevalent than either FIV or FeLV and is considered nonpathogenic in nature, is consistently coisolated from sick, FIV-infected cats. To determine the potential role of FeSFV in enhancement of FIV-mediated disease, persistent FeSFV infection was established in 14 of 24 nine-month-old cats. Four months later, half the FeSFV-infected and half the noninfected cats were inoculated with blood obtained from a cat persistently infected with the Petaluma strain of FIV. At postinoculation week 17, 1 male cat infected with only FIV died of bacterial bronchopneumonia that could have been attributed to FIV-induced acquired immune deficiency-like syndrome. However, none of the remaining cats had clinical illness, whether infected with either virus alone or coinfected with both viruses. As early as postinoculation week 6, decreases were observed in the CD4+ to CD8+ T-lymphocyte ratio of both groups of cats inoculated with FIV. Infection with FeSFV had no effect on the CD4+ to CD8+ T-cell ratio. Mitogen stimulation assays and total WBC count were unaffected by FeSFV infection, although an increase in numbers of neutrophils from FeSFV-infected cats was consistent, especially when compared with the decrease observed after FIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus.

The long terminal repeat (LTR) of a retrovirus contains sequence elements that constitute a promoter for controlling viral gene expression in infected cells. We have examined regulation of LTR-directed gene expression in feline immunodeficiency virus (FIV), a T-lymphocytopathic lentivirus associated with a fatal AIDS-like disease in domestic cats. Two independent virus isolates, designated FIV-Petaluma and FIV-PPR, have been molecularly cloned and show greater than 85% sequence homology. Both clones (termed pF34 and pPPR) produce infectious virus after transfection of permissive feline cells. Basal promoter activity of the LTRs was measured in various cell lines in transient expression assays using plasmids containing the viral LTR linked to the bacterial chloramphenicol acetyltransferase gene. Both LTRs were strong promoters in several cell lines, although in some cell lines the pF34 LTR had four- to fivefold higher basal activity than the pPPR LTR. FIV LTR mutations affecting the first AP4 site, AP1 site, ATF site, or NF-kappa B site resulted in decreased basal activity of the FIV promoter. Mutational analysis also revealed a negative regulatory element. In cotransfection experiments, both pF34 proviral DNA and pPPR proviral DNA appeared to transactivate either the pF34 LTR or the pPPR LTR; however, levels of transactivation were very low. Cotransfection of both LTRs with FIV subgenomic clones containing various viral open reading frames resulted in low level or no transactivation. The LTRs of both FIV clones responded to cell activation signals in human T-lymphoid cells (Jurkat) treated with phytohemagglutinin and phorbol-12-myristate-13-acetate. Promoter function of both FIV LTRs was also enhanced in cells treated with either forskolin, an inducer of intracellular cyclic-AMP (c-AMP), or dibutyryl c-AMP. Analysis of site-specific mutants showed that a potential AP1 site in the U3 domain of the LTR was required for T-cell activation responses mediated by protein kinase C, whereas a putative ATF site was the target for c-AMP-induced responses mediated by protein kinase A. These studies revealed that cellular transcription factors play a significant role in regulation of FIV gene expression.

Base Sequence↗
PubMed1992

Detection of feline immunodeficiency virus infection in bone marrow of cats.

Natural or experimental feline immunodeficiency virus (FIV) infection in cats is often associated with hematologic abnormalities which are similar to those observed in human immunodeficiency virus (HIV) infected patients. To determine if cells in bone marrow are infected with FIV and whether severity of hematopoietic disorder is correlated with the level of viral infection, bone marrow tissues from ten experimentally and two naturally FIV infected cats were examined by in situ hybridization for presence of FIV RNA. Seven of the 12 FIV infected cats were also naturally or experimentally coinfected with feline leukemia virus (FeLV). FIV RNA was detected mainly in megakaryocytes and unidentified mononuclear cells in the bone marrow of cats that were sick and had marrow hypercellularity and immaturity. These included all cats in the acute phase of FIV infection and two of seven long term FIV infected cats. One long term FIV infected cat with lymphosarcoma was also positive for FIV RNA in bone marrow cells. The other four long term FIV infected cats were relatively healthy, with normal bone marrow morphology, and were negative for FIV infected cells. Bone marrow from three non-infected and two cats infected with FeLV alone were also negative for FIV RNA by in situ hybridization. We concluded that megakaryocytes and mononuclear cells were targets of the viral infection and that the presence of FIV RNA in cells of the bone marrow correlated with marrow hypercellularity and immaturity, and severity of illness.

Animals↗
PubMed1992

Persistent upregulation of MHC class II antigen expression on T-lymphocytes from cats experimentally infected with feline immunodeficiency virus.

A significant elevation in the percentage of CD4+ and CD8+ T-lymphocytes expressing major histocompatibility complex (MHC) Class II antigens was observed in the blood of cats shortly after they were experimentally infected with feline immunodeficiency virus (FIV). In addition to an increase in the relative proportion of T-lymphocytes expressing Class II antigens, there was an increase in the density of Class II antigens on the cell surface. These elevations were still evident at the completion of the 5 month study. A second group of cats that had been infected with FIV for almost 5 years, and with either normal or abnormally low levels of CD4+ T-lymphocytes, had similar elevations in MHC II expression, suggesting that such abnormalities are lifelong. Cats with chronic (2 year) feline leukemia virus (FeLV) infection or dual FIV/FeLV infections also showed similar alterations in MHC II expression on CD4+ and CD8+ T-lymphocytes, suggesting that these alterations were not FIV specific. Feline T-lymphocytes expressed more MHC II antigen and interleukin-2 (IL-2) receptor following stimulation in vitro with conconavalin A and IL-2, demonstrating that feline T-lymphocytes respond to activation signals in a manner similar to T-lymphocytes of other species. However, changes in MHC II expression on T-cells of FIV infected cats were not explainable by viral induced T-cell activation alone, because FIV infected cats with elevated MHC II expression did not have coincident elevations in IL-2 receptor expression.

Animals↗
PubMed1992

Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency virus infections in experimentally infected specific pathogen free cats.

Cats with or without chronic feline immunodeficiency virus (FIV) infection were exposed to feline herpesvirus, type 1 (FHV-1). FIV infected cats became sicker than non-FIV infected cats and required more supportive treatment. However, there were no differences in the length of their illness or in the levels and duration of FHV-1 shedding. FHV-1 infection caused a transient neutrophilia at Day 7 with a rapid return to preinfection levels. The neutrophilia coincided with a transient lymphopenia that was accompanied by a decline in both CD4+ and CD8+ T-lymphocytes. A brief decrease in the CD4+/CD8+ T-lymphocyte ratio occurred at Day 14 in both FIV infected and non-infected cats. This decrease was mainly the result of an absolute and transient increase in CD8+ T-lymphocytes. CD4+ and CD8+ T-lymphocyte numbers and CD4+/CD8+ T-lymphocyte ratios returned to baseline within 4-8 weeks in both FIV infected and non-infected cats. FIV infected cats produced less FHV-1 neutralizing antibodies during the first 3 weeks of infection than non-FIV infected animals. The IgM FHV-1 antibody response was depressed in FIV infected cats whereas the IgG antibody response was unaffected. FHV-1 infection evoked a comparable transient loss of lymphocyte blastogenic responses to concanavalin A and pokeweed mitogen in both FIV infected and non-infected cats. However, response to pokeweed mitogen took longer to return to normal in FIV infected animals. Lymphocytes from FIV infected cats had a greater and more sustained proliferative response to FHV-1 antigen than non-FIV infected cats. The ongoing IgG antibody response to FIV was not affected by FHV-1 infection.

Acute Disease↗
PubMed1992

Inflammatory oral cavity diseases of the cat.

There is a great deal of frustration among veterinarians about the diagnosis and treatment of inflammatory diseases of the oral cavity of the cat. This frustration is due to both the high frequency of feline oral inflammatory lesions and our poor understanding of their causes. This poor understanding can be blamed on several things: (1) a rapidly emerging, but still relatively poor, understanding of feline diseases in general and nutrition in particular; (2) a tendency to lump rather than separate specific oral inflammations; (3) a tendency not to use a thorough and systematic approach to diagnosing oral cavity disease; and (4) the reluctance of veterinarians to apply what is already known about human oral cavity diseases to cats. When problems 2 through 4 are adequately addressed, it becomes apparent that we really know more about oral cavity disease in the cat than we thought we knew and that great progress has been made. The task ahead is to define, in precise medical terms, those remaining disease entities of the oral cavity that pose the greatest health risk to cats, to apply what has been already been discovered from human disease counterparts, and to study them systematically.

Animals↗
PubMed1992

Acute and chronic faucitis of domestic cats. A feline calicivirus-induced disease.

The lesions of acute feline calicivirus infection are of a transient vesiculo-ulcerative nature and involve, to varying degrees, the palate, tongue, gingiva, lips, nasal philtrum, and oral fauces. Chronic ulceroproliferative faucitis is a specific but uncommon sequelae to persistent feline calicivirus oral carriage.

Acute Disease↗
PubMed1992

Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy: oral 3'-azido-3'-deoxythymidine prevents SIV infection.

The prophylactic and therapeutic properties of 3'-azido-3'-deoxythymidine (AZT) against simian immunodeficiency virus (SIV) infection were tested in four 3-month-old rhesus macaques. The infant monkeys were inoculated intravenously with a low dose (1 to 10 100% animal infectious doses) of uncloned SIVmac. The monkeys were treated orally with 50 mg of AZT per kg of body weight every 8 h; two animals were started on treatment 2 h prior to virus inoculation, and two animals were started on treatment 6 weeks later. All four animals were treated for a period of 6 to 10 weeks. Outward signs of AZT toxicity were absent, but a mild macrocytic anemia occurred soon after therapy was started and resolved shortly after it was discontinued. The two infants that were begun on AZT treatment 2 h prior to virus inoculation never became infected, as demonstrated by the inability to detect cell-free or cell-associated virus in the blood, proviral DNA in peripheral blood mononuclear cells, or anti-SIV antibodies. AZT administration over a 10-week period had no detectable effect on the course of disease in the two animals that were begun on treatment after the infection had been established. In addition to demonstrating the prophylactic effect of AZT against low-dose SIV exposure, the study demonstrated the ease with which infant rhesus macaques can be used for antiretroviral drug testing.

Administration, Oral↗
PubMed1992

Characterization of morphologic changes and lymphocyte subset distribution in lymph nodes from cats with naturally acquired feline immunodeficiency virus infection.

Lymph nodes were collected at biopsy or necropsy from 18 cats with naturally acquired symptomatic feline immunodeficiency virus (FIV) infection and from 18 seronegative cats. Thirty-five of the cats were domestic shorthairs and one was a Persian cross. The cats ranged from 7 months to 16 years of age and were mainly obtained from California veterinary practitioners, a California cattery, and a Veterinary Teaching Hospital. Based on clinical signs present at tissue collection, ten FIV-infected cats fell into the acquired immunodeficiency syndrome (AIDS)-related complex (ARC) clinical stage and eight in the terminal (AIDS) stage of FIV disease. All cats were FeLV negative by antigen ELISA. Histologic sections of lymph nodes from each cat were examined blindly and were categorized as hyperplastic, involuting, mixed hyperplastic and involuting, depleted, or normal based upon subjective evaluation of follicles and paracortex. The relative abundance of plasma cells was evaluated in methyl green pyronin (MGP) and hematoxylin and eosin-stained sections. Similar numbers of FIV-seropositive and -seronegative cats fell into each lymph node category. The only difference evident between FIV-infected cats and control cats was in the degree of plasmacytosis present; moderate to marked plasmacytosis was present in 13/18 FIV-infected cats but in only 3/18 control cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cohort study of natural transmission and two methods for control of caprine arthritis-encephalitis virus infection in goats on a California dairy.

A prospective observational cohort study of 361 dairy goat kids was conducted to compare 2 methods of controlling caprine arthritis-encephalitis virus infection under commercial dairy conditions. To compare effectiveness of feeding kids pasteurized milk vs serologic testing and segregation in addition to pasteurized milk feeding, goats were monitored up to the age of 30 months by use of monthly agar gel immunodiffusion testing. Survival analysis methods were used to determine whether age at seroconversion differed between the 2 groups. Significantly lower rates of seroconversion were observed in the segregated group (P < 0.001), compared with the nonsegregated group. Of 193 goats in the pasteurized milk-only group, 146 (75.6%) seroconverted within the 30-month study period, whereas infection was detected in 39 (23.2%) of 168 goats in the test/segregated group. Nonsegregated goats were 3.37 times more likely to seroconvert by 24 months of age, and 70.3% of seroconversions by 24 months of age could be attributed to nonsegregation. For age-specific intervals beyond 180 days of age, 70 to 100% of seroconversions could be attributed to lack of segregation. Cohort life tables for age at seroconversion were reported for each group. Type of colostrum fed, sex, and weaning group (season) were not significantly associated with age at seroconversion. Saanen goats had lower age-specific risk of seroconversion in the nonsegregated group alone and overall. Non-Saanen goats wee 1.5 times more likely to seroconvert than were Saanen goats, when adjusted for a possible confounding effect of weaning group. Results indicate that pasteurized milk feeding and routine test and segregation would be a substantially more effective means of control of the disease in dairy goat herds than would pasteurized milk feeding alone.

Age Factors↗
PubMed1992

Risk factors associated with the incidence of seroconversion to caprine arthritis-encephalitis virus in goats on California dairies.

Incidence of seroconversion to caprine arthritis-encephalitis virus (CAEV) was determined for 1,194 goats on 11 dairies, using 2 repeated annual herd tests for CAEV. Current life table methods were used to compare age-specific incidence of seroconversion for pasteurized milk-raised and unpasteurized milk-raised goats. Logistic regression models were used to determine the risk factors associated with CAEV seroconversion, and to estimate odds ratios for seroconversion for various factor levels. Goats raised by unpasteurized milk-feeding methods were 2.5 to 6.7 times more likely to seroconvert than were goats raised by pasteurized milk-feeding methods, depending on the method of comparison. Similarly, 61.6 to 85.0% of seroconversions in yearling goats possibly were attributable to unpasteurized milk feeding. Among yearling goats, CAEV seroconversion was associated with feeding method, breed, and source of goat (herd of origin) when the effect of dairy was considered. In addition to the 6.7 times greater risk of seroconversion for unpasteurized milk-raised goats, yearling goats of the Saanen and Toggenburg breeds were 2.2 and 3.3 times, respectively, more likely to seroconvert than were Alpine yearling goats. Yearling goats purchased from another source were less likely to seroconvert than were yearlings raised on the dairy where they were studied. Among goats > 1 year old, age was associated with risk of seroconversion. Goats that were 3 years old or were > or = 4 years old were 1.7 and 3.2 times, respectively, more likely to seroconvert than were 2-year-old goats, when adjusted for effect of dairy. The effects of dairy were significant (P < or = 0.001) in yearling and older goats.

Age Factors↗
PubMed1992

Shared antigenic epitopes of the major core proteins of human and simian immunodeficiency virus isolates.

Antigenic epitopes on the major core (gag) protein of isolates of simian and human immunodeficiency virus (SIV and HIV) were compared using a panel of eleven mouse monoclonal antibodies (Mabs) that recognized nine distinct gag epitopes. Viral isolates used for comparison were HIV-1IIIb, HIV-2ROD, and SIV isolates from macaque (SIVmac), sooty mangabey (SIVsm-UCD), African green monkey (SIVagm), and stump-tailed macaque (SIVstm-UCD). The relatedness of the various HIV and SIV isolates, as determined by Mabs to core protein epitopes, paralleled that ascertained by genetic sequencing.

Antibodies, Monoclonal↗
PubMed1991

Study of feline leukemia virus immunity.

Fifteen specific-pathogen-free cats were experimentally infected with FeLV; 8 cats recovered after transient or nondetectable viremia, and 7 cats became persistently viremic. Four additional cats served as noninfected controls. Antibodies to whole FeLV (ELISA and immunoblot [western] analysis), antibodies to fixed FeLV-infected cells, and virus-neutralizing antibodies were monitored for as long as 3 years after infection. As a group, cats that recovered after acute infection developed higher titer of these various antibodies than did cats that became persistently viremic. However, specific combination or titer of antibodies was not always found in recovered cats or in persistently viremic cats. Six cats that had recovered from acute FeLV infection nearly 3 years earlier were reinfected with the same virus. Three of the cats appeared to be resistant to reinfection, 2 cats became transiently viremic, and 1 cat became persistently viremic. Slight and transient anamnestic ELISA-detectable antibody response to whole virus was seen after reinfection; immunofluorescence- and western blot-detectable responses were not greatly enhanced. Five FeLV-recovered cats were monitored for 2 years; FeLV infection spontaneously recurred in 1 cat.

Animals↗
PubMed1991

Neoplasia associated with feline immunodeficiency virus infection in cats of southern California.

Between 1988 and 1991, feline immunodeficiency virus (FIV) infection status was evaluated in 1,160 cats examined at an oncology referral and general practice in Los Angeles, California. Twenty-nine (2.5%) cats were FIV positive. Neoplasia was present in 18 of the 29 (62%) cats. Sampling for neoplasia was intentionally biased in the oncology referral group. However, 33% (6/18) of FIV-infected cats with neoplasia originated from the general practice. Three neoplastic processes were observed; myeloproliferative disease (MPD; 5/18), lymphoma (LSA; 5/18), and squamous cell carcinoma (SCC; 7/18). One cat had LSA and SCC. Extranodal sites of LSA were common (66%) in FIV-infected cats. Sites of LSA were submandibular and mesenteric lymph nodes, liver, kidneys, periorbital area, and diffuse (heart, pancreas, bladder). Sites of SCC were sublingual (n = 2), nasal planum (n = 3), nasal planum and eyelids (n = 1), and mandible (n = 2). Feline leukemia virus co-infection was observed in 17% (5/29) of FIV-infected cats. The FIV-infected cats with MPD were young (range, 8 months to 13 years; median, 4 years) and had short survival duration (2, 6, 21, 134, 249 days) even in response to aggressive treatment. The FIV-infected cats with LSA were older (median age, 8 years; range, 4 to 14 years) and survived 60 days if untreated. Cats administered chemotherapy survived 39, 45, 217, and 243 days; the latter 2 cats had partial remission of 2 months' duration. Older FIV-infected cats had SCC (median age, 12 years; remission range, 7 to 16 years) because of more frequent association of both diseases in older cats with outdoor environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

Comparative efficacy of three commercial feline leukemia virus vaccines against methylprednisolone acetate-augmented oronasal challenge exposure with virulent virus.

Three commercial FeLV vaccines, (A, B, and C) were purchased on the open market and administered to 8- to 20-week-old specific-pathogen-free kittens, according to manufacturers' instructions. A similar group of nonvaccinated kittens served as controls. All kittens were challenge-exposed oronasally with virulent FeLV 4 weeks after the final vaccination. Serum samples were monitored for FeLV-p27 antigenemia using an ELISA at 1- to 2-week intervals for at least 16 weeks after the last day of challenge exposure. Kittens that were either transiently (1 to 4 weeks) or never viremic during this period were counted as recovered, whereas kittens that became viremic and retained viremia for at least 10 weeks were counted as persistently viremic. The 3 vaccines were found to be 39% (vaccine C), 28% (vaccine B), and 17% (vaccine A) efficacious in preventing persistent viremia in immunized, compared with nonimmunized kittens.

Animals↗