Surgical treatment of aortic embolism in a cat.
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Animals↗
Biomedical subjects
L H Arp
Publications and source records attributed to L H Arp.
Tumor models: assessing toxicity in efficacy studies.
Efficacy studies in animal tumor models provide an early opportunity to collect preliminary information on toxicity. When screening and evaluating cytotoxic chemotherapeutic agents, efficacy studies usually include at least 1 dosage level that causes severe toxicity and death. Pathologic evaluation in early efficacy studies may reveal major target organs, dosage/schedule relationships, pharmacokinetic/toxicity relationships, effects of formulation and route of administration, maximum tolerated dose, cause of death, and reversibility of changes in normal tissues. Intraperitoneal formulations are frequently used to establish proof of concept for promising compounds (hits) from in vitro screens; however, these crude formulations may also induce intraperitoneal inflammation and confound the interpretation of both efficacy and toxicity. Efficacy studies conducted in the later stages of drug discovery may be used to refine the dose and schedule proposed for phase I clinical trials. Efficacy studies in animal tumor models provide useful toxicologic data for screening potential drug candidates, optimizing the therapeutic index, and designing both preclinical and clinical development programs.
Animals↗
Particle uptake by conjunctiva-associated lymphoid tissue (CALT) in turkeys.
Uptake of tracer particles was assessed in lower eyelid conjunctiva-associated lymphoid tissue (CALT) of 3-week-old turkeys. Tracer particle suspensions, including carbon, iron oxide, or three sizes of latex beads (0.81 micron, 1.7 microns, and 2.9 microns), were placed into the experimentally sealed conjunctival space. After 5, 15, or 30 minutes, eyelids were removed and CALT was examined by light microscopy. Uptake was confirmed for all tracers and occurred within the lymphoepithelium of CALT. The uptake of latex beads was not as frequent as for carbon and iron. Tracers were increasingly evident in lymphoepithelium and subepithelial macrophage clusters as contact time increased. These findings provide additional evidence that CALT is capable of antigen uptake and may play a role in paraocular and upper respiratory immunity in turkeys.
Animals↗
Quantification of particle uptake by conjunctiva-associated lymphoid tissue (CALT) in chickens.
Tracer particle uptake by conjunctiva-associated lymphoid tissue (CALT) was quantified in the lower eyelids of 1-, 3-, 5-, and 7-week-old broiler chickens. CALT was measured histologically by computerized image analysis in all birds and in additional 1-day-old and 16-week-old chickens not subjected to uptake assessment. Suspensions of carbon or iron oxide were placed in contact with CALT for 5, 15, or 30 minutes (contact time). After eyelid removal, tracer uptake was scored by light microscopy, CALT was measured, and a mathematically derived uptake index was evaluated statistically. At each age examined, computer-generated measurements showed a significant increase in the proportion of CALT lymphoepithelium within proximal eyelids. Within the conjunctival sites evaluated, tracer uptake was significantly greater in lymphoepithelium than in non-lymphoepithelium at all ages and at all contact times. Uptake increased significantly between 3 and 5 weeks of age and between 5 and 15 minutes of tracer contact. Based on these uptake data for CALT in chickens, a minimal age-specific maturity is suggested that may influence function in mucosal immunity.
Animals↗
A comparison of outer membrane proteins and surface characteristics of adhesive and non-adhesive phenotypes of Bordetella avium.
The outer membrane protein profiles of four adherent and one reduced-adherence mutant phenotype of Bordetella avium were compared; a non-adherent B. avium-like organism isolated from turkeys was also examined. The organisms were grown on brain-heart infusion agar at 35 C for 36 hours. In addition, one of the adherent phenotypes was grown at 18 C and 40 C. The outer membrane proteins were isolated by sonication and detergent extraction with Triton X-100. Surface characteristics of intact bacteria were examined using negative stain and transmission electron microscopy. The adherent phenotypes had identical protein profiles by electrophoresis. The non-adherent B. avium-like organism lacked at least five of the proteins present on the adherent strains. The non-adherent mutant phenotype had a protein profile similar to that of the adherent organisms, although several proteins were present in much lower concentrations. Fimbriae were found on both adherent and non-adherent organisms. By comparing protein profiles of adherent and non-adherent B. avium we were able to make a preliminary determination of the membrane proteins that lack adhesive properties.
Animals↗
Passive immunization versus adhesion of Bordetella avium to the tracheal mucosa of turkeys.
Three-week-old turkeys were passively immunized with convalescent serum or treated with tracheal washings from turkeys infected with Bordetella avium. Western blot analysis of the convalescent serum and tracheal washings revealed at least two bands of interaction with outer membrane protein preparations of B. avium. Adherence of B. avium in vivo to tracheal mucosa was determined and compared in treated and untreated turkeys. Passive immunization with convalescent serum reduced adherence of B. avium to the tracheal mucosa in a dose- and time-dependent manner. Adherence was significantly inhibited (P less than 0.01) when turkeys were treated intravenously with 1 ml of undiluted serum either 1 or 6 hours previously. Incubation of the bacterial inoculum with convalescent tracheal washings or application of the washings to tracheal segments before adherence determination in vivo resulted in a significant (P less than 0.01) decrease in adherence. These results indicate that adherence of B. avium to tracheal mucosa is inhibited by substances (antibody) present in both serum and tracheal secretions of convalescent turkeys.
Animals↗
Pulmonary clearance and lesions of lung and air sac in passively immunized and unimmunized turkeys following exposure to aerosolized Escherichia coli.
Two groups of young turkeys, one passively immunized with homologous hyperimmune serum and the other unimmunized but receiving normal turkey serum, were aerosolized with Escherichia coli. Clearance of bacteria from lung and gross and microscopic lung and air-sac lesions were determined after necropsy at timed intervals. The group mean bacterial count in lungs of passively immunized turkeys was significantly less than the mean count in unimmunized turkeys. Lung lesions were generally similar in both groups and were focused in lymphoid nodules, at the junction of primary and secondary bronchi, and at the ostia to the air sacs. Unimmunized birds developed grossly evident purulent airsacculitis by 72 hours after aerosol exposure, whereas passively immunized birds did not.
Air Sacs↗
Effects of Bordetella avium toxin on turkey tracheal organ cultures as measured with a tetrazolium-reduction assay.
Turkey tracheal organ cultures (TOCs) were exposed to one of the following Bordetella avium fractions or controls: live B. avium, formalin-killed B. avium, B. avium sonicate, heat-inactivated sonicate, culture supernatant, heat-inactivated culture supernatant, phosphate-buffered saline, or brain-heart infusion broth. After the TOCs were incubated for 2 hours with the bacterial fractions, the cellular metabolism of each TOC was evaluated using a tetrazolium chloride reduction assay, and cellular morphology was determined by light microscopy. Additionally, bacterial fractions and controls were injected into turkeys to test lethality. Although the bacterial sonicate was lethal for turkeys, neither the sonicate nor any other B. avium fraction significantly affected the metabolism or morphology of turkey TOCs.
Animals↗
Influence of temperature on the growth of Bordetella avium in turkeys and in vitro.
Effects of temperature on growth of three strains of Bordetella avium were determined in young turkeys and in vitro. Colonization of the tracheal mucosa by two virulent strains of B. avium was significantly greater in cold-stressed turkeys than in heat-stressed turkeys. The avirulent vaccine strain, ART-VAX, colonized tracheas of cold-stressed turkeys to a limited extent but failed to colonize heat-stressed turkeys. Growth rates of the three B. avium strains were determined in brain-heart infusion broth at 30, 35, 40, and 45 C. All three strains grew best at 35 C but were killed by 45 C. Compared with virulent strains, ART-VAX grew markedly less at all temperatures, and most cultures of ART-VAX grew at 40 C only after a variable period of declining numbers of viable bacteria. This study indicates that temperature affects growth of B. avium in vivo and in vitro and that growth of the ART-VAX strain is fundamentally different from growth of virulent strains.
Agglutination Tests↗
Pathology of the trachea in turkeys exposed by aerosol to lentogenic strains of Newcastle disease virus.
Five groups of 4-week-old turkey poults were each infected by aerosol with a different lentogenic strain of Newcastle disease virus. Four days postinfection, sections of tracheas were collected for histopathologic characterization and virus titration. The most prominent lesions were fibrinopurulent exudate in tracheal lumens, hyperplasia of epithelial cells, and infiltration by lymphocytes. All strains multiplied to high titers and produced similar microscopic lesions, but the number of poults with severe microscopic lesions varied among groups.
Aerosols↗
Progression of tracheal lesions in turkeys exposed by aerosol to LaSota strain of Newcastle disease virus.
Five-week-old turkeys were exposed by aerosol to the LaSota strain of Newcastle disease virus. Poults were killed on days 2, 4, 6, 8, 10, 12, and 14 postexposure, and tracheas were processed for virus quantitation and histologic examination. Newcastle disease virus was recovered at a high titer from all tracheas collected 2, 4, and 6 days postexposure. The initial tracheal lesion observed on day 2 was swelling of ciliated columnar and mucous gland cells. Some of the affected cells contained intracytoplasmic inclusions. Cell swelling and degeneration were followed by epithelial cell proliferation, fibrinopurulent exudation, and lymphocytic infiltration. Epithelial cell proliferation was most severe on days 4 and 6, when tracheas were lined with several layers of immature cells. Lymphoid nodules appeared on day 6 and persisted up to day 14. From day 8 on, there was regression of the proliferative lesion accompanied by differentiation of the immature epithelium. By day 14, the tracheal mucosa regained its normal histologic appearance.
Aerosols↗
Consequences of active or passive immunization of turkeys against Escherichia coli O78.
Turkeys were injected at 7 and 14 days of age with live, heat-killed or formalin-killed Escherichia coli O78. Other turkeys were passively immunized at 22 days of age with hyperimmune serum produced against live or heat-killed E. coli O78. All turkeys were challenged at 24 days of age with E. coli O78. Turkeys immunized intramuscularly or intratracheally with live E. coli O78 were protected from death, whereas few turkeys given killed E. coli O78 were protected. Passively immunized turkeys were protected from death regardless of whether live or heat-killed E. coli O78 was used to produce the hyperimmune serum. Most turkeys that survived challenge developed septic polysynovitis 2--4 days after challenge.
Animals↗
A time-course study of the transfer of immunoglobulin G from blood to tracheal and lacrimal secretions in young turkeys.
Three-week-old turkeys were injected intravenously with Bordetella avium-specific immunoglobulin G (IgG), and absorbance readings were measured in blood, tracheal washings, and lacrimal secretions using an enzyme-linked immunosorbent assay at various time intervals. IgG was detected in tracheal and lacrimal secretions as early as 5 minutes after injection and peaked at 10 minutes after injection. Thereafter, IgG absorbance declined rapidly, reaching background levels by 24 hours. The absorbance readings of IgG in all three sites were comparable at all times from 10 minutes to 24 hours after administration. The results indicated that movement of IgG from blood to mucosal surfaces in turkeys occurs rapidly.
Analysis of Variance↗
Mucosal and systemic humoral immune response to Bordetella avium in experimentally infected turkeys.
Antibody response to Bordetella avium was measured in serum and mucosal secretions of experimentally infected turkeys. Two-day-old turkeys were inoculated with B. avium, and four inoculated turkeys and four uninoculated control birds per trial were euthanatized weekly from 1 through 8 weeks postinoculation (PI). Maternal antibody of the IgG isotype, present in all 2-day-old birds sampled, decreased to background levels by 3 weeks of age. Antibody (IgG, IgM, IgA) was detected in serum, tracheal washings, and lacrimal secretions in response to B. avium infection. Regardless of the sample site and isotype, antibody levels peaked at 4-6 weeks PI and then decreased rapidly from 6 to 8 weeks PI. In general, IgM and IgA levels peaked earlier (4-5 weeks PI) but declined more rapidly than IgG levels. Numbers of B. avium in the trachea peaked at 2-3 weeks PI and then decreased rapidly from 4 to 8 weeks PI. Even though no direct causal relationship could be determined, the results indicate that an increasing level of antibody in serum, tracheal washings, and lacrimal secretions is temporally associated with clearance of B. avium from the trachea.
Aging↗
A monoclonal antibody-based latex bead agglutination test for the detection of Bordetella avium.
The purpose of this study was to develop a rapid method to distinguish Bordetella avium from closely related Bordetella avium-like and B. bronchiseptica bacteria. A monoclonal antibody of the IgM isotype was produced in Balb/c mice against live B. avium strain 75. The monoclonal antibody, in the form of ascites fluid, was added to a bovine serum albumin-glycine buffer (pH 8.6) and adsorbed to 3.03-microns-diameter latex beads. Optimum concentrations of antibody, beads, and bacteria were determined. The latex bead conjugate was tested against 40 isolates of B. avium, 24 isolates of B. avium-like bacteria, 17 isolates of B. bronchiseptica, two isolates of Alcaligenes faecalis, and several other common genera. Strong agglutination occurred with all B. avium isolates and the two isolates of A. faecalis. Weak agglutination occurred with Staphylococcus aureus and two isolates of B. bronchiseptica. There was no agglutination with any of the B. avium-like isolates. The latex bead agglutination test may be useful as an aid in the identification of B. avium when used in conjunction with other criteria.
Alcaligenes↗
Distribution and quantitation of plasma cells, T lymphocyte subsets, and B lymphocytes in bronchus-associated lymphoid tissue of chickens: age-related differences.
Development of the lymphoid cell compartment in bronchus-associated lymphoid tissue (BALT) of specific pathogen free chickens was examined. Specifically, B lymphocytes, T cell subsets (CD4 and CD8), and IgA-, IgG-, and IgM-producing plasma cells were labeled using immunocytochemical methods. Immunoglobulin-producing cells (IgPC) were quantitated, and comparisons of IgPC numbers were made among chickens of different ages, among immunoglobulin isotypes, and between lymphoid (BALT) and nonlymphoid (non-BALT) areas in the primary bronchus. At hatching, BALT was devoid of IgPC, but by 2 weeks of age cells producing IgA, IgG, and IgM were present. Initially, there were approximately equal numbers of IgA-, IgG-, and IgM-PC; after 2 weeks of age, however, IgG- and IgM-PC outnumbered IgA-PC. At all ages, IgPC were more numerous in non-BALT regions of the primary bronchus than in BALT regions. Small numbers of T and B lymphocytes were present in BALT from 1-day old chickens, but substantial populations of these cells were not seen until 1-2 weeks of age. T helper (CD4+) cells were found near B cell regions in BALT lymphoid nodules, while T cytotoxic/suppressor (CD8+) cells were more evenly distributed throughout the nodules and in the epithelium. B lymphocytes predominated in germinal centers and also overlapped CD4+ populations adjacent to germinal centers. Lymphocyte cell types needed to initiate and regulate immune responses are present in chicken BALT and may be involved in protecting poultry from respiratory pathogens.
Aging↗
Structure and development of bronchus-associated lymphoid tissue in conventionally reared broiler chickens.
The development of bronchus-associated lymphoid tissue (BALT) in conventionally reared broiler chickens of 1 day and 1, 2, 3, 4, 6, and 8 weeks of age was studied using light and electron microscopy (scanning and transmission). BALT in these chickens resembled other mucosa-associated lymphoid tissues (MALT) in that it was composed of an altered epithelium overlying a population of lymphocytes and contained potential antigen-presenting cells, such as macrophages and dendritic cells; high endothelial venules were also present. In contrast to other MALT, epithelial cells in chicken BALT were not of the M-cell type; i.e., they lacked large numbers of apical tubules and vesicles for specialized uptake of luminal antigens. There were age-related differences in size, number, and cellular composition of BALT nodules. Lymphoid nodules were progressively larger and more numerous with increasing age. Germinal centers were present in birds 2 weeks of age and older. BALT epithelium was primarily squamous and non-ciliated in 1-day and 1-week-old chicks, becoming progressively more columnar and ciliated in older chickens. Lymphocyte infiltration of the epithelium was extensive at 1 to 4 weeks of age; in older chickens, distinct epithelial and lymphocytic compartments were separated by connective tissue.
Animals↗