Experiments concerned with the immunogenicity, pathogenicity, and transmissibility of a recombinant vaccinia:Sindbis virus were conducted. The WR strain of the recombinant vaccinia:Sindbis virus was found to be infective for calves and mildly pathogenic, resulting in local tissue reaction. It was not transmissible to other calves. Also, it was found to be immunogenic when inoculated intradermally into calves, and antibody was produced against the parent vector virus (vaccinia) and the Sindbis antigen. Recombinant virus given IV to calves induced no detectable clinical signs, nor did the calves develop neutralizing antibodies. Furthermore, second-passage lesion material containing up to 10(7) tissue culture infective doses of the recombinant virus failed to induce development of lesions or illness in intradermally inoculated calves, and virus could not be recovered from the inoculation sites. In this series of experiments, this vaccinia recombinant given intradermally was immunogenic, mildly pathogenic at the local injection site only, and was not transmissible to contact animals, thus demonstrating the potential efficacy and safety of the WR strain of vaccinia virus when used as a live vector system in cattle.

The influence of immunosuppression by T-2 mycotoxin on the fungal disease aspergillosis was investigated in rabbits. Four groups of rabbits (groups 1A, 1B, 3A, and 3B) were given 0.5 mg of T-2 toxin/kg of body weight/day, PO; in addition, rabbits of groups 3A and 3B were exposed to aerosols of Aspergillus fumigatus conidia from days 7 through 16. Rabbits of groups 2A and 2B were exposed to A fumigatus aerosols, but were not given T-2 toxin, and rabbits of group 0 served as controls. Two rabbits of group 1A, 1 rabbit of group 1B, and 1 rabbit of group 3A died before scheduled necropsy. Rabbits of groups 1A, 2A and 3A were killed and necropsied on day 17, and the remaining rabbits (groups 0, 1B, 2B, and 3B) were killed and necropsied on day 28. Changes caused by T-2 toxin included leukopenia, marginal anemia, and increased number of and morphologic changes in nucleated erythrocytes by day 21, followed by a regenerative hematologic response. Serum alkaline phosphatase and sorbitol dehydrogenase activities and antibody response to A fumigatus (as measuredby an indirect hemagglutination test) were decreased by T-2 toxin ingestion. Rabbits with aspergillosis had leukocytosis, increased PCV, and increased antibody response to A fumigatus. Histologic lesions consisting of centrilobular hepatocellular swelling, portal and periportal fibrosis, and lymphocyte necrosis and/or depletion within secondary lymphoid tissue were observed in most rabbits treated with T-2 toxin. Normal defense mechanisms against A fumigatus infection were compromised by T-2 treatment, as evidenced by the severity and extent of lung lesions, greater number of hyphal elements observed, and greater number of colonies of A fumigatus isolated from rabbits of groups 3A and 3B. There were no significant changes in group-0 rabbits.

Large increases in systemic and pulmonary arterial pressures of exercising healthy ponies have been observed. Because exercise causes a considerable increase in PCV of ponies, we examined the effect of splenectomy on exercise-induced changes in systemic and pulmonary pressures. These pressures (taken with catheter-tip micromanometers) and indicator dilution cardiac output were determined on 9 healthy ponies that had undergone splenectomy 4 to 9 weeks before the study. Data obtained at rest and during submaximal (10.5 to 11.0 mph) and maximal (14 to 15 mph) exercise from these ponies were compared with similar data from clinically normal ponies. Following splenectomy, PCV increased by only 4 vol% during maximal exercise, but cardiac output of splenectomized ponies reached values similar to those of clinically normal ponies. Despite this similarity in cardiac output, the systemic and pulmonary arterial pressures of exercising splenectomized ponies increased to significantly lower levels than those in clinically normal ponies (P less than 0.01); total pulmonary vascular resistance and total peripheral resistance decreased to values significantly less than those in clinically normal ponies (P less than 0.01). Thus, it appears that increases in blood viscosity induced by increases in PCV may contribute substantially to the pulmonary and systemic hypertension of exercise in clinically normal ponies.

Effects of xylazine (1.1 mg/kg of body weight, IV bolus, plus 1.1 mg/kg/h infusion) and subsequent yohimbine (0.125 mg/kg, IV bolus) administration on the arrhythmogenic dose of epinephrine (ADE) in isoflurane (1.8% endtidal)-anesthetized dogs were evaluated. The ADE was defined as the total dose of epinephrine that induced greater than or equal to 4 premature ventricular contractions within 15 seconds during a 3-minute infusion period or within 1 minute after the end of infusion. Total ADE values during isoflurane anesthesia, after xylazine administration, and after yohimbine injection were 36.6 +/- 8.45 micrograms/kg, 24.1 +/- 6.10 micrograms/kg, and 45.7 +/- 6.19 micrograms/kg, respectively. Intravenous xylazine administration significantly (P less than 0.05) increased blood pressure and decreased heart rate, whereas yohimbine administration induced a significant (P less than 0.05) decrease in blood pressure. After yohimbine administration, the ADE significantly (P less than 0.05) increased above that after isoflurane plus xylazine administration. After yohimbine administration, blood pressure measured immediately before epinephrine-induced arrhythmia was significantly (P less than 0.05) less than the value recorded during isoflurane plus xylazine anesthesia. Heart rate was unchanged among treatments immediately before epinephrine-induced arrhythmia. Seemingly, yohimbine possessed a protective action against catecholamine-induced arrhythmias in dogs anesthetized with isoflurane and xylazine.

Strains of the suspensory ligament and deep digital flexor, superficial digital flexor, and long digital extensor tendons in the equine (pony) hind limb were recorded in vivo, using implanted strain gauges consisting of silicone rubber tubes filled with mercury. The relationship between strain gauge signals and tendon strains was obtained from tension-strain tests performed on isolated tendons after death of the ponies. During normal walking, maximal tendon strain (elongation over initial length, relative to the length of the structures at first ground contact) was 3.1% in the suspensory ligament and 3.4%, 2.3%, and 0.3% in the deep digital flexor, the superficial digital flexor, and the long digital extensor tendons, respectively. Changes (that occurred during walking) in the distance from origin to insertion of these musculotendinous structures were computed from limb geometric configuration and limb conformation. Maximal increase in origin to insertion length was 3.1% in the suspensory ligament and 2%, 1.6%, and 1.5% in the deep digital flexor, superficial digital flexor, and long digital extensor musculotendinous structures, respectively. The differences in strain, comparing the entire musculotendinous structure and its tendon, were explained by muscular contraction or relaxation.

Fifty-five horses were inoculated IV and/or SC with materials containing Ehrlichia risticii, ie, infected whole blood, buffy coat cells, or cell culture, to study clinical and hematologic features of equine monocytic ehrlichiosis (Potomac horse fever). Major clinical and hematologic features of induced E risticii infection were biphasic increase in rectal temperature with peak increases of 38.9 C and 39.3 C on postinoculation days (PID) 5 and 12, respectively; depression; anorexia; decreased WBC count (maximal decrease of 47% on PID 12); and diarrhea from PID 14 to PID 18. Increased WBC count was an inconsistent feature, with a maximal increase of 51.5% on PID 20. During times of decreased and increased WBC counts, lymphocyte/neutrophil ratios remained fairly constant. However, not all horses had all clinical and hematologic features, and these features were present in different degrees among horses. Increased rectal temperature, depression, anorexia, and decreased WBC count were more consistent features, whereas diarrhea developed in 73% of the horses. Of 55 horses, 39 (71%) had all clinical and hematologic features of the disease (classic disease), whereas 16 (29%) horses did not have greater than or equal to 1 of these features (nonclassic disease). The E risticii titer in the blood (ehrlichemia) was maximum during the peak increase in rectal temperature. In 55 horses, mortality was 9%. Significant differences (P > 0.5) in clinical and hematologic features were not detected between horses that survived and those that died of E risticii infection.

Studies were undertaken to assess the chicken embryo and newly hatched chicken as models for studying the effects of bone-active agents. Initially, 1,25-dihydroxycholecaliferol (1,25[OH]2D3), sodium fluoride (NaF), parathyroid extract, epidermal growth factor, and prostaglandin E2, were tested for lethality over a broad dose range. One or 3 injections of 1,25(OH)2D3 into the yolk sac of chicken embryos resulted in death of embryos given greater than 0.1 ng/injection, whereas 0.01 ng was tolerated by the embryos. Administering 1,25(OH)2D3 intraperitoneally to newly hatched chickens as a single injection or weekly for 3 weeks resulted in no deaths at doses up to 50 ng. One or 3 IV injections of less than 400 micrograms were tolerated by the embryo. Giving chickens feed and water containing 2.4 g of NaF/kg was lethal but no deaths occurred when chickens were given feed containing less than 1.2 g of NaF/kg. Mortality associated with the administration of epidermal growth factor to embryos was inconsistent, in that death occurred in embryos given a single injection of greater than 250 ng, but no deaths occurred in embryos given 3 injections at similar doses. Parathyroid extract and prostaglandin F2 were not lethal when administered to embryos and chickens in a single-injection or multiple-injection regimen. Overall, lethality in chicken embryos given a particular agent reflected the dose of bone-active agent injected, rather than the number of injections. Three of the bone-active agents were selected to characterize their microscopic bone effects in chicken embryos and chickens. Administration of 1,25(OH)2D3 to embryos on day 14 at doses of 100, 10, 1, and 0.1 ng led to subperiosteal hyperosteoidosis in all 5 of the tibiotarsi examined from the high-dose (100 ng) group necropsied on day 18 of incubation. Three of 5 of the tibiotarsi from the 10-ng treatment group were similarly affected. Bone effects were noticed in chickens hatched from the aforementioned treatment groups or in chickens given 1,25(OH)2D3 intraperitoneally and examined at 3 and 6 weeks of age. Administration of NaF to chicken embryos on the 10, 12th, and 14th days of incubation via the IV route at doses of 160, 80, 40 and 20 micrograms/embryo led to subperiosteal hyperosteoidosis in tibiotarsi from 3 of 10 embryos (examined at 18 days of incubation) from the 2 high-dose groups. Tibiotarsi of chickens from this treatment group were microscopically normal at 3 weeks after hatching. When newly hatched chickens were given a diet containing NaF at dosages of 1.2 g/kg, 0.6 g/kg, and 0.3 g/kg, a dose-dependent increase in osteoid was seen at 3 and 6 weeks. In addition, cortical thinning and expansion of the medullary canal were observed only at 3 weeks. In contrast to the effects observed with 1,25(OH)2D3 and NaF, parathyroid extract caused no microscopic bone alterations when given to embryos or chickens. Overall, the bone alterations in the embryo were attributed to increased subperiosteal osteoid formation and defective mineralization. These findings were consistent with known effects of NaF and 1,25(OH)2D3 on bone, and they establish the chicken embryo as a sensitive model for studying bone-active agents.

The effect of glucocorticoids on early follicular growth in sows undergoing normal estrous cycles was evaluated by administration of dexamethasone during the middle of the luteal phase. Plasma specimens were obtained for measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and estradiol-17 beta concentrations. Fifteen sows were used. Control sows (n = 5) were given physiologic saline solution twice daily from day 9 to day 14 of the estrous cycle. Sows of the second group (n = 5) were given dexamethasone (30 microgram/kg of body weight, IM) similarly, and those of the third group (n = 5) were given dexamethasone plus gonadotropin-releasing hormone (GnRH+ 50 microgram at 6-hour intervals, IV). Plasma specimens, obtained twice daily from day 8 through day 26, indicated that progesterone production and luteal regression were not inhibited by any of the 3 treatment regimens. Although preovulatory plasma estradiol concentration increased in control sows, such was not observed in the sows treated with dexamethasone or dexamethasone plus GnRH (P less than 0.01). Ovulation, with formation of corpora lutea, occurred in gilts given saline solution. Dexamethasone administration resulted in persistence of 19 to 41 follicles/ovary (2 to 4 mm in diameter), and dexamethasone-plus-GnRH treatment resulted in 6 to 18 follicles/ovary (5 to 6 mm in diameter). Plasma was obtained at 15-minute intervals for 12 hours to compare the effect of treatmenton hormone concentrations on day 12 of the estrous cycle with the values on day 8. Glucocorticoid administration had no significant effect on mean concentration, final concentration excluding those hormone concentrations that constituted part of a pulse (referred to as base line), number of pulses, pulse amplitude, and area under the pulse for either gonadotropin. Addition of GnRH to dexamethasone treatment significantly (P less than 0.01) increased all plasma LH values, but only base-line concentration of FSH. For estradiol, pulse amplitude and mean pulse area were increased (P less than 0.05), and although the frequency of pulses was not significantly altered, base-line concentration in glucocorticoid-treated sows was significantly reduced, compared with that of control sows. In sows treated with GnRH plus dexamethasone, the pulse frequency of estradiol was significantly (P less than 0.01) increased, but pulse area and amplitude were similar to those of sows given saline solution. Dexamethasone treatment was associated with an increase in mean and base-line concentrations of progesterone. The results suggest that high midcycle glucocorticoid concentrations (1) do not inhibit luteal function or regression, (2) have little influence on LH and FSH secretion during the middle of the luteal phase, (3) alter the pattern of estradiol secretion, (4) are associated with the persistence of small ovarian follicles, and (5) result in the development of fewer but larger follicular structures when GnRH is administered concurrently.

A significant (P less than 0.0001) positive correlation was demonstrated between left ventricular internal chamber dimension in diastole or systole and body weight, body surface area, cycle length, and the square root of cycle length. On the basis of adjusted coefficients of determination, multiple regression analysis, using body weight or body surface area and cycle length or the square root of cycle length, was superior to separate simple regression with these variables in accounting for variations in left ventricular internal chamber dimensions. Shortening fraction had a significant (P less than 0.0001) negative correlation and left ventricular free wall measurements had a significant (P less than 0.0001) positive correlation to body weight and body surface area. For these echocardiographic variables, correlation to the square root of cycle length was insignificant (P greater than 0.05), and a multiple regression model was not helpful in developing confidence intervals. Septal wall measurements were not correlated with body weight, body surface area, cycle length, or the square root of cycle length.

Twenty-four male domestic shorthair cats were used to evaluate the acute and chronic effects of a single, toxic but sublethal, orally administered dose of chlorpyrifos. A dose of 10 mg/kg of body weight did not induce clinical signs of toxicosis, but a dosage of 40 mg/kg induced clinical signs of toxicosis, and 1 of 12 cats died. Chlorpyrifos given at a dosage of 0.1 mg/kg to 2 cats reduced whole blood and plasma cholinesterase (Che) activities to values obtained after cats were given doses that induced clinical signs of toxicosis. Regeneration time for whole blood and plasma Che activities ranged from 7 to 28 days. Brain Che activity was considerably decreased in 1 cat that died 4.5 hours after dosing, but was normal in all others at 28 days after dosing. Other than decreased Che activity, significant changes were not seen in hematologic or serum biochemical values. Toxin-related lesions were not seen during macroscopic or microscopic examination.