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Biomedical subjects

P F Moore

Publications and source records attributed to P F Moore.

At least 91 records · Page 5Linked to original sources
PubMed1992

Monoclonal antibodies specific for canine CD4 and CD8 define functional T-lymphocyte subsets and high-density expression of CD4 by canine neutrophils.

The characteristics of canine homologues of CD4 and CD8, defined by murine monoclonal antibodies CA13.1E4 (IgG1) and CA9.JD3 (IgG2a) respectively, are described. These antibodies identify mutually exclusive subpopulations of non-B lymphocytes in peripheral lymphoid organs and blood. However, in thymus the antibodies defined populations of double-positive, double-negative and single-positive cells that showed a progressive maturation consistent with that described for CD4 and CD8 in other mammalian species. Furthermore, functional studies clearly associated cytotoxic effector cell function with the subpopulation reactive with CA9.JD3 (CD8). In contrast, proliferation stimulated by allogeneic cells and mitogens was more pronounced in the subpopulation reactive with CA13.1E4 (CD4). Cell and tissue distribution studies revealed that CA13.1E4 stained neutrophils with equivalent intensity to the staining of peripheral T cells. CA13.1E4 precipitated a 60 kD protein from the surface of T cells and highly purified neutrophils under both reducing and nonreducing conditions. CA9.JD3 precipitated a heterodimer of 32 kd and 36 kD under reducing conditions, and a 70 kD protein under non-reducing conditions. The expression of CD4 by canine neutrophils is without precedent in other mammalian species; the functional significance of neutrophil CD4 expression is puzzling in light of the current understanding of the functions of CD4 which include it's role as a receptor for nonpolymorphic regions of MHC class II molecules.

Animals↗
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

Langerhans cells, macrophages and lymphocyte subsets in the cervix and vagina of rhesus macaques.

BACKGROUND: The lower reproductive tract is an important site of contact with pathogenic microorganisms and local immune responses to a variety of antigens have been reported. The purpose of this investigation was to define the morphology of the mucosa-associated lymphoid tissue in the genital tract of rhesus monkeys. EXPERIMENTAL DESIGN: Monoclonal antibodies were used in an immunoperoxidase staining technique to identify immunophenotypic markers on mononuclear cells in the vaginal and cervical mucosa of 14 cycling, multiparous rhesus macaques. RESULTS: CD1a+ Langerhans cells were present in the stratified squamous epithelium of the vagina (14 animals) and ectocervix (11 animals). Surprisingly, CD1a+ dendritic cells were also found within the columnar epithelium of the endocervix (5 animals). Moderate numbers of CD68+ macrophages were located in the submucosa of the vagina, ectocervix, and endocervix of all the monkeys. In all of the animals, moderate numbers of CD8+ lymphocytes were present in the submucosa and squamous epithelia of the vagina and ectocervix. Variable numbers of CD20+ B cells and CD4+ lymphocytes were located in the submucosa of all the areas examined. Lymphoid nodules were present in the submucosa of vagina (14 animals) and ectocervix (4 animals), and these nodules contained macrophages, CD4+ T cells and B cells, with fewer numbers of CD8+ T cells and Langerhans cells. CONCLUSIONS: These observations provide a morphologic basis for mucosa-associated lymphoid tissue in the female genital tract. Langerhans cells in the vaginal mucosa and endocervix may be well suited to sample antigen in the lumen of the reproductive tract, travel to the draining lymph node, present the antigen to T lymphocytes and initiate an immune response. This pathway of antigen presenting cell migration from the mucosa to the genital lymph node may represent the inductive arm of the mucosal immune system in the lower female reproductive tract.

Animals↗
PubMed1991

Structure-activity relationship of quinazolinedione inhibitors of calcium-independent phosphodiesterase.

A series of quinazolinediones and azaquinazolinediones is described which possess potent inhibitory activity toward the calcium-independent phosphodiesterase enzyme (CaIPDE). In vivo testing showed that this in vitro activity translates to animal models predictive of chronic diseases such as depression and inflammation. These results support the hypothesis that inhibition of CaIPDE may lead to useful activity in such chronic diseases.

Animals↗
PubMed1991

Pathologic studies of acute rejection of mismatched feline musculocutaneous flaps. Effect of cyclosporine and prednisolone.

The gracilis musculocutaneous flap was developed as an allograft model to study acute rejection and immunosuppression in the cat. Twelve adult cats received a MLC incompatible flap. Six of the cats received cyclosporine oral solution and prednisolone (0.5 mg/kg/24 hr) for 100 days and six cats were not treated. Trough whole-blood levels of cyclosporine in the treatment group were maintained at approximately 750 ng/ml for 70 days, then 500 ng/ml for the remaining 30 days. Three flaps failed due to technical problems; 5 flaps were studied in the treatment group and 4 in the untreated group. All 5 flaps in the treatment group survived the 100 day treatment period and were rejected 30 +/- 26 days following cessation of treatment. Prior to discontinuation of treatment, with the exception of one cat, inflammatory changes associated with rejection were not observed in biopsy specimen. The flaps in the untreated group survived 13 +/- 1.5 days. Histopathologic examination of the flaps revealed little difference in the appearance of acute rejection and rejection after cessation of therapy. The most prominent lesion was a vasculitis with extensive perivascular lymphohistocytic inflammation. The lymphoid infiltrates consisted predominantly of T cells of both major classes (CD4 and CD8). Full-thickness epidermal necrosis and subsequent bacterial invasion followed vascular compromise.

Animals↗
PubMed1991

Acquired immune dysfunction in cats with experimentally induced feline immunodeficiency virus infection: comparison of short-term and long-term infections.

Specific pathogen-free domestic cats with experimentally induced feline immunodeficiency virus (FIV) infections of short duration (less than or equal to 10 months) exhibited depressed total leukocyte and neutrophil numbers and a marginally decreased lymphocyte proliferative response to pokeweed mitogen (PWM), while cats with infections of more lengthy duration (greater than or equal to 25 months) exhibited normal leukocyte and neutrophil numbers but a dramatic loss of responsiveness to both PWM and concanavalin A (Con A). Cats with short-term infections exhibited a decrease in the percentage of CD4+ lymphocytes in peripheral blood and a corresponding depression of the CD4+:CD8+ ratio. Cats with long-term infections exhibited a similar but more profound perturbation of the CD4+ lymphocyte subset that also included a decrease in the absolute number of CD4+ cells. The decreased responsiveness to Con A and PWM in cats infected long term paralleled the decline in CD4+ cell counts, and the duration of infection was directly correlated with the decrease in the percentage of CD4+ cells. These data provide evidence supporting the hypothesis that FIV is the cause of an immune dysfunction in cats, with distinct similarities to that produced by human immunodeficiency virus (HIV) in people.

Acquired Immunodeficiency Syndrome↗
PubMed1991

C-reactive protein as an index of disease activity. Comparison of tenidap, cyclophosphamide and dexamethasone in rat adjuvant arthritis.

C-reactive protein (CRP) concentrations are a useful plasma protein measure that correlate with disease severity and radiographic progression in rheumatoid arthritis (RA). We compared 3 drugs with different mechanisms, i.e., tenidap, dexamethasone and cyclophosphamide, on both CRP levels and soft tissue swelling in the rat adjuvant arthritis model. CRP rose from a normal concentration of approximately 400 micrograms/ml during the first phase of adjuvant arthritis to approximately 1200 micrograms/ml (primary response), then fell to approximately 900 micrograms/ml and rose again as the disease became systemic during the secondary response to approximately 1400 micrograms/ml. When treatment was administered prophylactically, tenidap and dexamethasone suppressed both the primary and secondary CRP and swelling responses. Cyclophosphamide was without effect in the primary response, but inhibited both swelling and CRP in the secondary response. When therapeutic treatment was begun after secondary disease was established, only tenidap and dexamethasone inhibited CRP and swelling. Both dexamethasone and cyclophosphamide decreased lymphocyte numbers during treatment whereas lymphocyte numbers were elevated during tenidap treatment, suggesting a different mechanism of action for tenidap. CRP levels were more closely linked to the rate of change of paw swelling (disease progression) than to paw volume.

Animals↗
PubMed1990

1,2-Dihydro-1-oxopyrrolo[3,2,1-kl]phenothiazine-2-carboxamides and congeners, dual cyclooxygenase/5-lipoxygenase inhibitors with antiinflammatory activity.

A series of 1,2-dihydro-1-oxopyrrolo[3,2,1-kl]phenothiazine, 1,2-dihydro-1-oxopyrrolo[3,2,1-kl]phenoxazine, and 1,2-dihydro-1-oxopyrrolo[3,2,1-de]acridine-2-carboxamides were prepared by reaction of 1,2-dihydro-1-oxo-pyrrolo[3,2,1-kl]phenothiazine or other corresponding phenoxazine and acridan ethyl or methyl esters with appropriate amines. Several members of this family were found to be potent, dual inhibitors of cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism and to have in vivo antiinflammatory activity in the rat foot edema assay. Structure-activity relationships within this family of compounds are described. 1,2-Dihydro-N-(2-thiazolyl)-1-oxopyrrolo[3,2,1-kl]phenothiazine-1- carboxamide (34) was found to be one of the best compounds to display potent cyclooxygenase/5-lipoxygenase inhibition of arachidonic acid metabolism. Its IC50s against the enzymes sourced from rat basophillic leukemia-1 (RBL-1) cells were 0.07 and 1.4 microM, respectively. It was active in the rat foot edema test for antiinflammatory effect (48% inhibition at 33 mg/kg po) and in the mouse phenylbenzoquinone induced writhing test for analgesic effect (93% inhibition at 32 mg/kg po).

Animals↗
PubMed1990

Canine leukocyte integrins: characterization of a CD18 homologue.

The major characteristics of the canine CD18 leukocyte antigen family, defined by a murine monoclonal antibody CA1,4E9, are described. The overall molecular organization of this family of leukocyte integrins was similar to the human counterpart, and consisted of a common beta subunit of 95 kD (CD18) and non-covalently linked alpha subunits of 150 kD (CD11C), 165 kD (CD11b) and 180 kD (Cd11a). Conservation of CD18 epitopes between dog, human, feline, equine and bovine was observed. CD18 expression in lymphoid tissue had a characteristic pattern which was based on differences in the intensity of expression observed in different cell types. The expression of LeuCAMs in canine epidermotropic lymphosarcoma (mycosis fungoides) was also explored since LeuCAMs might be expected to play a major role in the tissue tropism of this tumor. Intense CD18 expression was observed in the malignant T cells which infiltrated the epidermis; these cells differed phenotypically from dermal T cells in that they often lacked Thy-1 expression. The potential pathogenetic significance of LeuCAM expression in canine mycosis fungoides is discussed.

Animals↗
PubMed1990

Distribution of MHC class II antigens in feline tissues and peripheral blood.

A new monoclonal antibody raised against gradient-purified feline immunodeficiency virus was found to recognize a bimolecular complex, comprising 27-29 kD and 32-35 kD subunits, on feline peripheral blood lymphocytes. Immunoperoxidase staining of feline tissues with this antibody, designated 43.2H2, demonstrated a reactivity pattern similar to that described for MHC II antigens of the dog, horse, and pig, but differed from human and mouse in having staining of T-cell zones in spleen and lymph nodes. Flow cytometric analysis revealed that 42.3H2 reacted with 88.97% +/- 16.00% of feline peripheral blood lymphocytes (n = 20). This high level of reactivity was found to be consistent by repeated sampling over a 4-month period. Two-color flow cytometric analysis was used to determined the reactivity pattern on lymphocyte subsets: 88.92% +/- 7.30% of CD4+ lymphocytes were 42.3H2-positive, while 85.99% +/- 11.46% of CD8+ cells were positive (n = 11 for both). B lymphocytes had the highest reactivity (99.47% +/- 0.45; n = 9) and also had the highest fluorescence intensity. By gating based on light scatter properties, 95.06% +/- 7.35% of monocytes were 42.3H2-reactive (n = 18), while granulocytes were negative.

Animals↗
PubMed1990

The pathogenesis of experimental bluetongue virus infection of calves.

Eleven seronegative calves were intravenously inoculated with bluetongue virus (BTV) serotype 10, and two calves were inoculated with a placebo. Cellular association of BTV during viremia was investigated in three of the calves by titrating virus present in plasma and different blood cell fractions at weekly intervals after infection. Viremia persisted 35 to 49 days in individual calves. Virus was transiently isolated from blood mononuclear cells and plasma collected from two of the calves but was consistently isolated from erythrocytes throughout infection of all three animals. Titers of BTV present in the erythrocyte fraction were comparable to those of the unseparated blood cell fraction. Tissue tropism of BTV was determined by viral isolation from tissues collected from calves euthanatized at 1, 2, 3, 4, 5, 7, 14, 28, 42, and 56 (2 calves) days after inoculation with BTV. Tropism was also determined by immunohistochemical staining of selected tissues with an avidin-biotin complex immunoperoxidase staining procedure using three BTV-specific monoclonal antibodies. The BTV infected calves remained healthy throughout the study. Virus was isolated from at least one tissue collected from calves euthanatized at 1 through 28 days after inoculation, but not thereafter. High titers of BTV were present in the lungs, prescapular and mesenteric lymph nodes, thymus, and spleen of calves euthanatized at 1 to 4 days after inoculation, whereas BTV was either not isolated or isolated in low titer from bone marrow collected from these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Immunohistochemical localization of type D retrovirus serotype 1 in the digestive tract of rhesus monkeys with simian AIDS.

Type D retrovirus infection of rhesus macaques (Macaca mulatta) shares many features with AIDS in man including gastrointestinal signs such as chronic diarrhea and wasting. In some humans and macaques afflicted with these signs and symptoms no etiology can be established. In this study immunohistochemistry was employed to localize D/1/California in the digestive tract of ten animals with simian AIDS. This revealed that both epithelial and lymphoid cells of the digestive tract are commonly infected by this immunosuppressive type D retrovirus.

Animals↗
PubMed1989

Indeno[1,2-c]pyrazolone acetic acids as semirigid analogues of the nonsteroidal anti-inflammatory drugs.

A series of 3-substituted indeno[1,2-c]pyrazol-4(1H)-one-2-acetic acids (3a-e) and 3-substituted indeno[1,2-c]pyrazol-4(1H)-one-1-acetic acids (4a-e) were synthesized as semirigid analogues of tolmetin (1). These compounds were evaluated for their anti-inflammatory action by investigating their ability to block arachidonic acid metabolism in vitro as well as the ability to block carrageenan-induced rat foot edema in vivo. No consistent pattern of biological activity was noted.

Animals↗
PubMed1989

Effects of dazmegrel, piroxicam and cyclophosphamide on the NZB/W model of SLE.

To investigate the potential importance of prostaglandins and thromboxane in systemic lupus erythematosus (SLE), the effects of a nonsteroidal antiinflammatory drug (piroxicam) and a thromboxane synthetase inhibitor (dazmegrel) were examined on survival, proteinuria, food consumption, body weight, and peripheral lymphocyte subset distribution in the NZB/W model of autoimmune lupus disease. The effect of an immunosuppressant (cyclophosphamide) known to be effective in the treatment of murine lupus on these parameters was also examined. Cyclophosphamide at 25 mg/kg ip weekly prolonged survival, inhibited proteinuria and prevented the characteristic decline in peripheral T cells and the relative increase in B cells seen in NZB/W lupus disease while having no apparent effect on body weight or food consumption. Neither dazmegrel at 50 or 200 mg/kg/day in the diet nor piroxicam at 2 mg/kg/day in the diet had any significant effects on these parameters.

Animals↗
PubMed1989

Bluetongue virus infection of bovine monocytes.

Cultures of adherent and non-adherent bovine blood mononuclear cells were infected with bluetongue virus (BTV) serotype 10. Production of BTV proteins in mononuclear cell cultures was detected by immune precipitation of viral proteins from [35S]methionine-labelled extracts of these cells, by immunofluorescence staining of cells using monoclonal antibodies (MAbs) to BTV proteins VP7 and NS2, and by flow cytometry with MAbs to VP2, VP7, NS1 and NS2. BTV-infected cells were most numerous in cultures of adherent mononuclear cells; infected cells were initially identified as monocytes on the basis of their morphology, and size and scatter characteristics as determined by analysis with a fluorescence-activated cell sorter (FACS). The majority of adherent mononuclear cells with these scatter characteristics were confirmed to be monocytes by FACS analysis with a MAb specific for bovine monocytes. Identification of BTV-infected adherent mononuclear cells as monocytes was further established by double immunofluorescent labelling, as infected adherent cells reacted with the MAb specific for bovine monocytes, and with another MAb specific for class II antigen. Infection of adherent mononuclear cells was also confirmed by transmission electron microscopy, as BTV virions and tubules were present in lysates of cultures of BTV-infected adherent mononuclear cells and within the cytoplasm of adherent cells. In contrast, BTV proteins were detected in few cells identified as lymphocytes on the basis of their scatter characteristics, and mean fluorescence of such cells was considerably less than that of BTV-infected monocytes. Viraemia persisted until 35 days after inoculation of a colostrum-deprived calf inoculated with BTV. Virus was isolated from blood mononuclear cells at 1 week after infection of the calf, but not thereafter. BTV infection of blood mononuclear cells was demonstrated until 9 days after inoculation by indirect immunofluorescence staining of mononuclear cells. In contrast, virus was consistently isolated from erythrocyte-enriched preparations throughout viraemia in titres comparable to those in whole blood. These results indicate that although bovine monocytes are readily infected in vitro with this strain of BTV serotype 10, infection of blood monocytes is unlikely to be responsible for the prolonged viraemia that consistently occurs in BTV-infected cattle.

Animals↗
PubMed1989

Mucosal epithelial cells and Langerhans cells are targets for infection by the immunosuppressive type D retrovirus simian AIDS retrovirus serotype 1.

Simian acquired immune deficiency syndrome (SAIDS) caused by the type D retrovirus SRV-1 results in opportunistic infections and a spectrum of oral lesions similar to those seen in humans with AIDS. To better understand the pathogenesis of these oral lesions we have retrospectively examined the oral mucosa from ten rhesus monkeys that died with SAIDS and prospectively examined the oral mucosa of ten additional animals inoculated with SRV-1 to determine at what time, and in what cells SRV-1 infection of the oral mucosa occurs. Using single and double label immunohistologic techniques, and electron microscopy we detected SRV-1 in clusters of oral epithelial cells and rare Langerhans cells as early as 1 month postinoculation.

Animals↗
PubMed1988

Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues.

Simian acquired immune deficiency syndrome (SAIDS) in rhesus macaques (Macaca mulatta) at the California Primate Research Center is caused by a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). This syndrome is characterized by profound immunosuppression and death associated with opportunistic infections. Neurologic signs and lesions have not been described as part of this syndrome. The distribution of SRV-1 in the salivary glands, lymph nodes, spleens, thymuses, and brains of eight virus-infected rhesus macaques was examined by immunohistochemistry. Electron microscopy, in situ RNA hybridization, and Southern blot hybridization were also performed on selected tissues to detect viral particles, RNA, and DNA, respectively. In seven of eight SRV-1-infected animals, the transmembrane envelope glycoprotein (gp20) of SRV-1 was present in three or more tissues, but never in the brain. In the remaining animal, no viral antigen was detected in any tissue. In this same group of animals, viral nucleic acid was detected in the lymph nodes of six of six animals by Southern blot hybridization, in the salivary glands of two of five animals by both Southern blot and in situ hybridizations, and, surprisingly, in the brains of three of three animals by Southern blot and of three of five animals by in situ hybridization, including the one animal in which viral gp20 was undetectable. None of these animals had neurologic signs or lesions. The detection of viral nucleic acid in the absence of viral antigen in the brain suggests latent SRV-1 infection of the central nervous system.

Acquired Immunodeficiency Syndrome↗