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Biomedical subjects

F W Quimby

Publications and source records attributed to F W Quimby.

At least 37 records · Page 2Linked to original sources

Friendliness to humans and defensive aggression in cats: the influence of handling and paternity.

This study was undertaken to examine and reduce the stress and aggressiveness associated with fear of handling in laboratory cats (Felis sylvestris catus). Thirteen litters of kittens from a specific pathogen-free breeding colony were divided into three treatment groups: two were early weaned, removed from the colony and caged individually with or without handling up to 8 weeks of age, and the third served as a control group, removed from the colony just before testing. Behavior tests measuring degree of friendliness to humans and response to physical restraint were performed at ages 8, 12, 16, and 20 weeks. Serum cortisol concentrations were measured after each test. Results indicate that litter and sire influenced tractability but that handling or individual caging of kittens did not. Posttest serum cortisol concentrations were below normal adult levels in most kittens, including those reacting fearfully during testing and aggressively during restraint, and, therefore, are not a reliable indicator of stress in juvenile cats.

Aggression↗

Twenty-five years of progress in laboratory animal science.

During the past 25 years tremendous improvements have been made in the field of laboratory animal science. Refinements in genetic and microbial quality assurance and animal housing coupled with the development of professional expertise has contributed to enhanced animal well-being and a reduction in the variability of data collected from research animals. These advances occurred concomitant with an increased public awareness of research animal use. In 1967 Laboratory Animals Ltd. published the first issue of Laboratory Animals. In celebration of its Silver Jubilee, I will briefly highlight some of the changes which occurred in the field of laboratory animal science since 1967 and some of the medical advances which depended on animal-based research.

Animal Diseases↗

A cytotoxicity assay for Clostridium spiroforme enterotoxin in cecal fluid of rabbits.

Clostridium spiroforme enterotoxin-mediated diarrhea can be a common cause of mortality among weanling age rabbits. Definitive diagnosis of this disorder requires detection of the causative enterotoxin. Using filtered cecal supernatant from necropsy specimens, antibodies to C. spiroforme and its products and Vero cells, a cytotoxicity assay was performed on 22 rabbits with clinical signs and lesions consistent with C. spiroforme enterotoxin-mediated diarrhea. A cytotoxic effect was detected, generally within 4 h, in 18 of 22 rabbits. The cytotoxic effect was blocked by preincubation of the cecal material with antibodies to C. spiroforme and its products. Culture of cecal contents and smears of cecal contents identified C. spiroforme in 10/22 and 12/22 cases, respectively. This cytotoxicity assay provided a rapid and sensitive method for diagnosing C. spiroforme enterotoxin-mediated diarrhea.

Animals↗

A canine febrile disorder associated with elevated interleukin-6.

Familial Mediterranean Fever (FMF) is a human disorder characterized by recurrent fever of unknown origin (RFUO), renal amyloidosis, and evidence of peritonitis, pleuritis, and/or synovitis. This report suggests that Chinese Shar-pei (CSP) dogs suffer from a similar syndrome. CSP dogs with RFUO (n = 15) showed greater levels of IL-6 in serum than normal controls, hypergammaglobulinemia, and normal or supranormal in vitro lymphocyte blastogenesis in response to mitogen stimulation, when compared to healthy afebrile dogs. In patients 2 years old or older, RFUO was associated with renal failure, renal amyloidosis, and swollen joints. An epidemiological survey of privately owned dogs indicated a RFUO prevalence of 23% in CSP dogs (n = 132) and 1% in dogs of all breeds (n = 98). Increased levels of circulating cytokines, such as IL-6, have been shown to influence such processes as the febrile response, antibody production, and the synthesis of amyloid precursors. We propose that CSP dogs with RFUO, renal amyloidosis, and joint inflammation may serve as an animal model of FMF and that the clinical syndrome is associated with elevated levels of circulating IL-6.

Amyloidosis↗

Tissue renin and prorenin increase in female cats during the reproductive cycle without commensurate changes in plasma, amniotic or ovarian follicular fluid.

The renin gene is expressed, primarily as prorenin, in the ovary, uterus and placenta. High concentrations of prorenin are present in human ovarian follicular and amniotic fluids and ovarian secretion causes increases in plasma prorenin at mid-menstrual cycle and during pregnancy. Plasma prorenin is low but detectable in nephrectomized human subjects. Comparative studies in female cats revealed several differences. Cat plasma prorenin became undetectable after bilateral nephrectomy. Neither plasma prorenin nor renin increased during pregnancy. Renin and prorenin were undetectable in ovarian follicular, amniotic and allantoic fluids. Human chorionic gonadotropin-induced ovulation caused only small increases in plasma prorenin. In contrast, renin and prorenin were clearly present in extracts of reproductive tissues. Ovarian total renin was lowest during anestrus (169 +/- 27 ng/g per h) and estrus (258 +/- 58 ng/g per h) and increased with ovulation (385 +/- 31 ng/g per h). Higher ovarian levels were found during pseudopregnancy (1370-2030 ng/g per h) and early pregnancy (1312-2700 ng/g per h) and in the placental chorion disc of early pregnancy (1755-1184 ng/g per h). In the uterus, the level was 98-183 ng/g per h during gestation. These results demonstrate that, in marked contrast to humans, only the cat kidney secretes prorenin into body fluids. Nonetheless, total renin increases in cat ovaries during follicle maturation, ovulation, pregnancy and pseudopregnancy, in the uterus during gestation and in the placental chorion disc. These results are consistent with an autocrine or paracrine role for the tissue renin system in cat reproductive tissues.

Amniotic Fluid↗

Lymphomas in dogs. A morphologic, immunologic, and clinical study.

One hundred seventy-six canine lymphomas were classified morphologically using four of the major human lymphoma classification schemes (Rappaport, Lukes-Collins, Kiel, and the Working Formulation). All 176 dogs received the same chemotherapeutic protocol. Sixty-two of these lymphomas had their immunophenotypes established by examination of cell surface markers by automated cytofluorography. Several different morphologic types of canine lymphoma were identified and these were comparable to morphologic categories in human classification schemes. Follicular and low grade lymphomas were rare. The two most common morphologic types were diffuse large cell (centroblastic) and immunoblastic. The Kiel classification appeared to be the most useful human scheme for classifying the canine lymphomas. Cytofluorographic analysis was generally straightforward, and 60 of the 62 lymphomas were placed into one of three immunophenotypic categories: 27 pan-T(LQ1)+SIg+, 21 pan-T(LQ1)-SIg+, and 12 pan-T(LQ1)+SIg-. Two of the lymphomas could not be characterized immunologically because a pre-existing or reactive non-neoplastic population of lymphocytes made interpretation of single cell suspension analysis difficult. The authors identified correlations between morphology and survival and disease-free remission; dogs with high-grade tumors generally survived the longest and had the longest remissions. No correlations were identified between high concentrations of serum lactate dehydrogenase, age, sex, or stage of disease, and morphology, immunophenotype, remission, or survival times. A significant correlation between clinical illness and survival time was documented. The median age of the dogs was nine years, no significant effect of sex on prevalence was observed, and some breeds were significantly overrepresented. Significant morphologic-immunophenotypic correlations included shorter remission and survival times for T-cell tumors than B-cell tumors, and a highly significant correlation between the pan-T(LQ1)+SIg-"T cell" phenotype and hypercalcemia.

Animals↗

Monoclonal antibodies directed at human T lymphocyte activation antigens cross react with concanavalin A-stimulated canine and baboon peripheral blood lymphocytes.

A panel of 10 monoclonal antibodies directed at activation antigens on human T lymphocytes were tested for cross reactivity with canine and baboon resting and ConA stimulated peripheral blood lymphocytes. Monoclonal antibodies anti-OKT19, anti-OKT-21, and anti-OKT22 labeled a high percentage of both resting and stimulated canine and baboon cells. Anti-OKT24 labeled activated but not resting baboon lymphocytes and did not label canine lymphocytes. Anti-HLA-DR labeled a small percentage of resting baboon lymphocytes (presumably B cells) and a high percentage of activated baboon and resting and activated canine lymphocytes. Anti-OKT14, anti-OKT20, and anti-OKT23 did not label canine or baboon lymphocytes. Anti-OKT9 did not label baboon lymphocytes, but labeled a low percentage of lymphocytes in one dog. Anti-TAC labeled activated but not resting canine and baboon cells.

Animals↗

Investigation of cross-reactivity between commercially available antibodies directed against human, mouse, and rat lymphocyte surface antigens and surface markers on canine cells.

Using automated flow cytometry, 23 commercially available antibodies (all but one of them monoclonal) raised against surface antigens of specific populations of human, rat, and mouse lymphocytes were tested for cross-reactivity to peripheral blood lymphocytes from five clinically healthy adult dogs. Of all the antibodies tested, only the polyclonal anti-asialo GM1 directed against mouse NK cells, and the monoclonal antibodies anti-HLA-DR directed against the human class II antigen and anti-B1, a human pan B cell marker, consistently labeled subpopulations of canine lymphocytes.

Animals↗

Effects of concanavalin A, phytohemagglutinin, pokeweed mitogen, and lipopolysaccharide on the replication and immunoglobulin synthesis by canine peripheral blood lymphocytes in vitro.

Canine peripheral blood lymphocytes (cPBLs) were used to investigate the mitogenic effects of Con A (concanavalin A), LPS (lipopolysaccharide), PHA (phytohemagglutinin), and PWM (pokeweed mitogen) in vitro by measuring tritium-labeled thymidine [( 3H]thymidine) incorporation and immunoglobulin (Ig) secretion. An ELISA specific for canine IgG and IgM showed that cPBLs secreted significantly more IgG than IgM in response to mitogen concentrations from 30,000 to 0.03 ng/10(5) cells. The optimal stimulating dose of mitogen for lymphocyte response measured by IgG secretion was over a much narrower range of concentration than was the [3H]thymidine incorporation measured response. At a concanavalin A dose where there was increased [3H]thymidine incorporation with a decrease in IgG secretion, it appeared that an active suppression of the IgG response was induced.

Animals↗

The development of a male pseudohermaphroditic rat using an inhibitor of the enzyme 5 alpha-reductase.

Incomplete masculinization of the external genitalia occurred in male Sprague-Dawley rats treated with a potent inhibitor of enzyme 5 alpha-reductase at the critical period of sexual differentiation in utero. The studies were performed using the 5 alpha-reductase inhibitor, 4-methyl-4-aza-5-pregnan-3-one-20[s] carboxylate, one of a series of aza steroids known to competitively inhibit the enzyme 5 alpha-reductase. The degree of inhibition of male external genital development was dependent upon the dose of the inhibitor, and at a dose of 36 mg/kg X day, there was complete feminization of the external genitalia of the male animal with a urogenital sinus and a pseudovagina. These studies provide conclusive evidence for the hypothesis that 5 alpha-reductase activity and dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) formation are essential for normal differentiation of male external genitalia. Epididymidis, vasa deferentia, and seminal vesicles were present at all doses of the inhibitor, suggesting testosterone dependency. However, confirmation of the testosterone dependency of Wolffian ductal differentiation awaits further studies, particularly comparison studies with the rabbit and dog, since Wolffian ductal differentiation in the rat, unlike the rabbit and dog, is not abolished with the antiandrogen, cyproterone acetate. The presence of prostatic buds, despite complete external genital feminization, was unexpected and suggests that these structures may have different thresholds of response for dihydrotestosterone. Prostatic differentiation may have a much lower threshold, requiring less dihydrotestosterone for differentiation.

5-alpha Reductase Inhibitors↗

Propylthiouracil-induced immune-mediated disease in the cat.

An immune-mediated disease was produced in 9 of 17 (53%) normal healthy cats by daily p.o. administration of 150 mg of 6-propylthiouracil (PTU). This disease syndrome is characterized by lethargy, weight loss, lymphadenopathy, hemolytic anemia, a positive direct antiglobulin test (DAT) and antinuclear antibodies (ANA). The duration of drug administration before the development of a positive DAT and/or ANA ranged from 3 to 8 weeks (Mean +/- S.E.M. = 4.5 +/- 0.6), whereas the duration before the onset of clinical signs ranged from 4 to 8 weeks (6.1 +/- 0.6 weeks). On cessation of PTU administration, clinical signs resolved in all cats within 2 weeks, and the DAT and test for ANA were negative within 1 to 4 weeks (1.9 +/- 0.4 weeks). During nine PTU-rechallenge periods in four cats, both the mean time to develop a positive DAT and ANA (2.5 +/- 0.8 weeks) and the mean time to develop overt clinical signs (2.6 +/- 0.7 weeks) were shorter than similar mean times in the initial PTU treatment period (P less than .01). During nine episodes of PTU-induced disease in seven cats, PTU administration was discontinued and replaced with 150 mg of 6-propyluracil (PU), a nonsulfur analog of PTU. Resolution of both clinical and serologic signs of disease occurred in seven of the nine disease episodes within 1 to 3 weeks (2.1 +/- 0.4 weeks). In the two cats whose disease did not resolve on PU, one was sacrificed after 1 week of PU administration, without clinical or serologic resolution, because of the severity of the PTU-induced disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic, Autoimmune↗

Analysis of the mitogenic effects of toxic shock toxin on human peripheral blood mononuclear cells in vitro.

It has been shown previously that the staphylococcal enterotoxins A and B are T-cell mitogens and also cause inhibition of murine plaque-forming cells generated in vitro. Similarly, toxic shock toxin, a 24,000-MW protein produced by toxic shock-associated strains of Staphylococcus aureus, is mitogenic and inhibits the generation of both murine and rabbit plaque-forming cells. In this study, an analysis of the T-cell response to toxic shock toxin was performed. Human peripheral blood mononuclear cells responded to toxic shock toxin over a broad dosage range (1 ng/ml to 5 micrograms/ml) with maximum proliferation at day 4 (96 hr) of culture. Heat treatment (100 degrees C for 60 min) of toxic shock toxin attenuated its mitogenic effects by only a small amount, and this attenuation could be reversed with increasing concentration of the toxin. By cytofluorography, both untreated and toxic shock toxin-treated small lymphocytes manifested normal percentages of OKT3+, OKT11+, OKT4+, OKT8+, HLA/DR+, and Leu-7+ cells. However, toxic shock toxin-induced blasts were 99% OKT11+ and expressed the receptor for interleukin 2 (89%-100% TAC+). Approximately 85% of the blasts were OKT4+, and 25% of the blasts were OKT8+. Proliferation of purified, double-rosetted T cells was enhanced monotonically by the addition of irradiated "non-T" cells. Irradiated, monocyte-enriched non-T cells were 2.5 times more potent than unfractionated non-T cells in producing quantitatively similar proliferation by toxic shock toxin-stimulated, autologous T cells. In addition, preincubation of non-T cells for 24 hr with toxic shock toxin, followed by extensive washing and irradiation, induced substantial proliferation by unexposed, autologous T cells. These data show that toxic shock toxin is mitogenic for T cells and requires accessory cells for maximal activity. Further, this substance appears to induce both a subset of OKT4+ (Class II MHC-restricted) and OKT8+ (Class I MHC-restricted) blasts.

Antigen-Presenting Cells↗

Adrenal function in the cat: comparison of the effects of cosyntropin (synthetic ACTH) and corticotropin gel stimulation.

The serum cortisol responses of 10 normal cats to natural adrenocorticotrophic hormone (ACTH) gel and synthetic ACTH (cosyntropin) were evaluated and compared. Following administration of either ACTH gel or cosyntropin, mean serum cortisol concentrations increased significantly (P less than 0.05) within 30 minutes and reached a maximal response (2.5 to 10 times basal values) at 90 minutes. The time to reach peak serum cortisol concentrations was variable, however, and occurred sooner after cosyntropin (30 to 60 minutes) than after ACTH gel administration (90 to 180 minutes). While ACTH gel tended to produce a prolonged cortisol response, the effects of cosyntropin were more transient, with serum cortisol concentrations returning to normal range within three hours after injection. Results of this study indicate that the administration of either ACTH gel or cosyntropin consistently produces an adequate adrenocortical response in the cat. Based on the time response studies, post ACTH cortisol samples should be collected 60 to 90 minutes after cosyntropin or 90 to 120 minutes after ACTH gel injection to ensure detection of peak adrenocortical response with either ACTH preparation.

Adrenal Cortex↗

Characterization of spontaneous amyloidosis of Syrian hamsters using the potassium permanganate method.

Amyloid from 16 Syrian hamsters with spontaneous age-related systemic amyloidosis retained affinity for Congo red dye after treatment with potassium permanganate. Serum electrophoresis showed a slight rise in gamma globulins without a monoclonal spike. Bence-Jones proteins were not present in the urine. There was no histological evidence of plasmacytosis. Amyloidosis could not be associated with chronic inflammation. The lack of apparent etiology of this amyloid and its resistance to potassium permanganate treatment suggests that it is a primary non-AA amyloid. This finding varies with a report suggesting that the spontaneous amyloidosis of aged Syrian hamsters is associated with the AA fibril.

Amyloid↗

A radiolabeled staphylococcal protein A assay for detection of anti-erythrocyte IgG in warm agglutinin autoimmune hemolytic anemia of dogs and man.

A cell wall protein from Staphylococcus aureus, Protein A, (SpA) has been shown to have the ability to bind the Fc region of most mammalian IgG molecules. This study uses this unusual property as the basis for a quantitative assay for erythrocyte (RBC) bound antibodies. Test serum is incubated in a suspension of normal RBC's. The cells are then washed and incubated with 125Iodine-labeled SpA (125I-SpA). After incubation cells are pelleted and bound radiolabeled SpA counted. This procedure has been performed using canine anti-goat RBC (DagRBC) serum and human anti-D serum (positive controls) to establish the kinetics of the SpA reaction in the above system. The results indicate that SpA binds to red blood cells as a function of membrane bound antibody. RBC's incubated with indirect Coombs positive sera bound 42.6% and 43.3% of the 125I-SpA, as compared to 19.2%, the upper limit of the 95% confidence interval (n = 9) for normal sera. Furthermore, significant binding was observed for certain indirect Coombs negative (direct Coombs positive) sera indicating that the SpA assay is more sensitive than the indirect Coombs test. The SpA system should provide the clinician with an inexpensive, sensitive, quantitative assay for the diagnosis of warm agglutinin autoimmune hemolytic anemia, as well as other autoimmune disorders involving membrane bound IgG.

Anemia, Hemolytic, Autoimmune↗

Efficacy of immunoserodiagnostic procedures in the recognition of canine immunologic diseases.

Six immunologic tests were conducted on a large population of dogs with a variety of diseases. The test results were analyzed retrospectively and correlated to the clinical and final pathologic diagnoses. The results indicated that rheumatoid factor and the direct antiglobulin (Coombs) test were both sensitive and specific for the diagnoses of canine rheumatoid arthritis and autoimmune hemolytic anemia. The antinuclear antibody test was useful in supporting the diagnosis of systemic lupus erythematosus (SLE) only when both antibody titer and the staining pattern were taken into consideration. The lupus erythematosus cell test was specific but not sensitive when used to confirm a diagnosis of canine SLE. Cellulose acetate serum electrophoresis and immunoelectrophoretic techniques were each useful in supporting the diagnosis of multiple myeloma. Epizootiologic data collected in this study indicated that dogs with primary immunologic disease had a poor prognosis. A female predisposition was observed in cases of canine autoimmune hemolytic anemia and SLE. Ovariectomy seemed to prevent the development of canine SLE.

Agammaglobulinemia↗