Studies on coronary arteriopathy in dogs following administration of CI-1020, an endothelin A receptor antagonist.

A selective nonpeptide endothelin A (ETA) receptor antagonist, CI-1020, was administered to beagle dogs intravenously (i.v.) for 4 hours to 4 weeks. One animal/sex received CI-1020 at 1 mg/kg/hr intravenously for 4, 8, or 24 hours to investigate onset of arteriopathy. Control animals (1/sex) received the vehicle only. To determine reversibility of arteriopathy, 8 dogs/sex were given CI-1020 at 1 mg/kg/hr for 4 days. Two dogs/sex were sacrificed 1, 3, 8, and 29 days following cessation of infusion. Lesion development with prolonged exposure was investigated in 1 male dog. It was given CI-1020 by i.v. bolus at 120 mg/kg/day for 4 weeks and Monastral blue dye was administered i.v. to facilitate localization of vascular lesions. Coronary blood flow was determined in 4 dogs infused with CI-1020 at 0.3, 3, and 30 mg/kg for one hour at each dose. Macroscopically, hemorrhage or blue discoloration of Monastral blue was noted in the extramural coronary arteries along the coronary groove and atrium. Histologically, the earliest coronary changes were noted in animals sacrificed after 24 hours of treatment and characterized by medial hemorrhage and necrosis with a few infiltrating neutrophils. In the reversibility study, incidence and severity of arteriopathy was dependent on time of sacrifice following cessation of infusion. Acute necrotizing inflammation of arteries was present in all animals (n = 4) on day 1 postinfusion, whereas on day 8 postinfusion, lesions characterized by medial small pockets of trapped red cells, cell debris, and adventitial thickening were seen in 1 dog/sex. By day 29 postinfusion, coronary arteries were similar to controls. In the dog given daily i.v. bolus injections of CI-1020 for 4 weeks, arterial inflammatory lesions varied from acute to chronic, although most lesions were considered chronic active. Monastral blue pigments were noted in the wall of most arteries with chronic or chronic active lesions. Acute lesions were similar to those noted in day 1 postinfusion of the reversibility study. Medial smooth muscle necrosis and/or fibrosis with mixed inflammatory cell infiltrates characterized chronic or chronic active lesions. Smooth muscle proliferation and migration into the intima were also noted. There were no significant changes in coronary blood flow, coronary vascular resistance, or mean arterial blood pressure following CI-1020 infusion for 3 hours. In the 24-hour infusion study, plasma endothelin 1 (ET-1) levels were mildly elevated (1.5-4 fold) during CI-1020 infusion when compared to either pretest or control values. These results indicate that administration of endothelin antagonist (CI-1020) to dogs was associated with development of coronary arteriopathy, which was completely resolved within 29 days following cessation of treatment. With prolonged (4-week) CI-1020 treatment, arterial lesions at varying stages of development (acute, chronic active, chronic) were seen, suggesting that tolerance to treatment (up to 4 weeks) does not occur.

Spontaneous thrombosis in mice carrying the factor V Leiden mutation.

A polymorphism in coagulation factor V, factor V Leiden (FVL), is the major known genetic risk factor for thrombosis in humans. Approximately 10% of mutation carriers experience clinically significant thrombosis in their lifetime. In a small subset of patients, thrombosis is associated with coinheritance of other prothrombotic gene mutations. However, the potential contribution of additional genetic risk factors in the majority of patients remains unknown. To gain insight into the molecular basis for the variable expressivity of FVL, mice were generated carrying the homologous mutation (R504Q [single-letter amino acid codes]) inserted into the endogenous murine Fv gene. Adult heterozygous (FvQ/+) and homozygous (FvQ/Q) mice are viable and fertile and exhibit normal survival. Compared with wild-type mice, adult FvQ/Q mice demonstrate a marked increase in spontaneous tissue fibrin deposition. No differences in fetal development or survival are observed among FvQ/Q, FvQ/+ or control littermates on the C57BL/6J genetic background. In contrast, on a mixed 129Sv-C57BL/6J genetic background, FvQ/Q mice develop disseminated intravascular thrombosis in the perinatal period, resulting in significant mortality shortly after birth. These results may explain the high degree of conservation of the R504/R506 activated protein C cleavage site within FV among mammalian species and suggest an important contribution of other genetic factors to the thrombosis associated with FVL in humans. (Blood. 2000;96:4222-4226)

Coronary arteriopathy in monkeys following administration of CI-1020, an endothelin A receptor antagonist.

A selective non-peptide endothelin A (ETA) receptor antagonist, CI-1020, was administered to cynomolgus monkeys intravenously (i.v.) for 2 or 4 wk and orally for 4 wk. Groups consisting of 3 animals of each sex received CI-1020 at 1, 5, and 10 mg/kg/hr (i.v.) or orally at 250, 500, and 750 mg/kg body weight for 4 wk. Control animals received the vehicle only. In a separate experiment, 1 male was infused with 10 mg/kg/hr for 2 wk, and Monastral blue dye was administered i.v. to facilitate localization of lesions to the vascular walls. One female was administered saline and the dye and served as a control. One female at 1 mg/kg/hr was found dead at week 2, and 1 female at 5 mg/kg/hr was euthanatized during week 4 as a result of severe thigh swelling at the catheter site. Macroscopically, extramural coronary arteries appeared thickened and nodular in the 4-wk i.v. study in the female found dead at 1 mg/kg/hr, in 1 male and 1 female at 5 mg/kg/hr, and in 2 females at 10 mg/kg/hr. Histologically, Monastral blue pigment trapped in the walls of coronary arteries with arteriopathy was observed in the male treated with CI-1020 at 10 mg/kg/hr for 2 wk. Extramural coronary arteriopathy occurred at all doses in the 4-wk i.v. study, with higher incidence occurring in females than in males (7 of 9 treated females compared with 3 of 9 treated males). In the oral study, 1 female at 500 mg/kg/day and 1 male and 2 females at 750 mg/kg/day had coronary arteriopathy. Histological changes after 2 wk of treatment were characterized by intimal thickening, fragmentation of the internal elastic lamina, necrosis and edema of the media, and mixed inflammatory-cell infiltrates in the intima, media, and adventitia. After 4 wk of i.v. administration, arteriopathy was characterized by segmental disruption of the elastic lamina and intimal and medial fibrosis with complete replacement of smooth muscle with fibrous tissue. The adventitia was thickened as a result of fibrosis and mixed or mononuclear inflammatory-cell infiltrates. CI-1020 concentrations were higher in males (1.57 to 29 micrograms/ml) than in females (0.974 to 24.4 micrograms/ml) in the i.v. study. Transient systemic exposure with high maximum plasma concentration (Cmax) (120-352 micrograms/ml) in the oral study was insufficient to provoke arterial changes of the same magnitude as those noted with continuous i.v. administration. The regeneration of the media by fibrous tissue and the disruption of the elastic lamina may weaken the arterial wall and increase the susceptibility of the artery to the development of aneurysm.

A novel model of venous thrombosis in the vena cava of rabbits.

The objective of this study was to develop and validate a new experimental model of venous thrombosis in the rabbit. A 3-cm length of siliconized PE tubing was used as a veno-venous shunt inserted into the abdominal vena cava of anesthetized rabbits. The PE tubing contained six cotton threads which helped to restrict blood flow through the tubing and served as a foreign, thrombogenic surface upon which a thrombus could develop. By continuously measuring blood flow through the vena cava, the rate of thrombus development can be monitored until zero flow is achieved indicating that a completely occlusive thrombus is present. The shunt can be removed making it possible to weigh the thrombus and/or determine its composition. A second shunt can be placed in the vena cava to make a second determination of time to occlusion and thrombus weight, using the data from the first shunt as an internal control standard for comparison. Reproducibility of the technique was demonstrated in a control group (n = 7) in which two successive shunts were used without an antithrombotic intervention. In studies with the first and second shunts, time to occlusion averaged 20.6+/-5.2 min and 20.2+/-5.7 min (pNS), respectively. The net thrombus weights (less the wet weight of the cotton threads) were 49.0+/-3.5 mg and 47.0+/-3.3 mg (pNS). Histologic examination of the thrombi indicated that they were largely composed of fibrin and red blood cells, consistent with the characteristics of venous thrombi. The low molecular weight heparin (LMWH) enoxaparin was used as an antithrombotic intervention to validate the model. Dose-dependent changes in time to occlusion and thrombus weight were achieved which paralleled alterations in coagulation parameters (thrombin time and activated partial thromboplastin time) and bleeding time determined with an ear bleeding technique. The veno-venous shunt model is easy to use, reproducible, and responds appropriately to an antithrombotic intervention, indicating that it should be useful for experimental evaluation of antithrombotic agents designed for venous thromboembolic disorders.

Streptococcal cell wall-induced arthritis: requirements for IL-4, IL-10, IFN-gamma, and monocyte chemoattractant protein-1.

Intra-articular injection of streptococcal cell wall Ag followed by i.v. challenge ("reactivation") results in a destructive lymphocyte-dependent monoarticular arthritis. To further define the role of immune mechanisms in the model, Abs to Th1 and Th2-related cytokines were evaluated. Treatment of rats with antibodies to IL-4 reduced swelling, while treatment with anti-IL-10 or anti-IFN-gamma either had no effect or slightly enhanced the inflammatory response. These results suggest that Th-2 immune mechanisms may be, at least in part, operative in the model. To more precisely define the role of IL-4, the effects of anti-IL-4 on monocyte chemoattractant protein-1 (MCP-1) expression were evaluated. Initial studies demonstrated that mRNA (as determined by in situ hybridization) and protein (as determined by immunofluorescence) for MCP-1 were detectable in inflamed synovial tissue in a time-dependent manner. Anti-IL-4 treatment significantly reduced the expression of mRNA for MCP-1 24 and 72 h after reactivation. In addition, anti-MCP-1 inhibited swelling and reduced influx of (111)In-labeled T cells. These data suggest that the reactivation model of streptococcal cell wall Ag-induced arthritis is Th-2 dependent, and that an inter-relationship exists between IL-4 and the expression of MCP-1.

Critical subcellular targets of cisplatin and related platinum analogs in rat renal proximal tubule cells.

The clinical usefulness of chemotherapeutic agents containing the platinum moiety is often limited by their nephrotoxicity. To investigate the mechanism of nephrotoxicity, and to assess the effects of platinum analogs on specific organelles and basal protein synthesis, biochemical and ultrastructural analyses were performed in rat renal proximal tubule cells (RPTCs). Neutral red (NR) uptake was used to measure lysosomal function, and conversion of MTT to formazan used to assess mitochondrial function. Despite their differential toxicity, cisplatin, carboplatin and CI-973 caused similar progressive inhibition of specific functions, suggesting they may share a common mechanism of nephrotoxicity. Protein synthesis was the earliest indicator of toxicity, followed by NR uptake and MTT conversion. Fluorescent probes for lysosomes (acridine orange) and mitochondria (rhodamine 123) confirmed that cisplatin's toxicity to RPTCs was delayed and cumulative. Condensation of nucleolar components and fragmentation of RER were observed in RPTCs treated for as little as two hours. Since the nucleolus is the site of ribosome biogenesis, the early inhibition of protein synthesis by cisplatin may arise from disruption of this region. In contrast, mitochondrial dysfunction and swelling were late-stage events, and are therefore unlikely to be the primary targets of nephrotoxic platinum compounds.

Hepatic and adrenal toxicity of a novel lipid regulator in beagle dogs.

PD 138142-15 is a substituted urea hypolipidemic and potential anti-atherosclerotic agent. To determine the toxicity of PD 138142-15, beagle dogs were given oral doses of 1, 10, 30, and 100 mg/kg daily for 13 weeks. Two animals at 100 mg/kg were euthanized during Week 5 due to poor condition. Clinical findings included decreased serum albumin at > or = 30 mg/kg, and increased ALP (up to 30-fold) and 5'-nucleotidase activities (up to 9-fold) at doses > or = 10 mg/kg. ALT and AST activities were elevated only at 100 mg/kg. There was a two- to threefold increase in cytochrome P450 content of hepatic microsomes from all treated animals and increases in liver weights at 10 mg/kg and above. Hepatic changes included hepatocellular hypertrophy and increased cytoplasmic eosinophilia at > or = 10 mg/kg; single cell necrosis of hepatocytes was noted in moribund animals. ACTH-stimulated cortisol levels were decreased at 30 and 100 mg/kg. Adrenal cholesterol esters were decreased at 10 mg/kg and above, while total adrenal cholesterol was decreased at > or = 30 mg/kg. These changes correlated with adrenal cortical zonal atrophy, principally of the zona fasciculata and zona reticularis, present at 30 and 100 mg/kg. Plasma concentrations of PD 131842-15 increased with increasing dose; plasma levels were significantly lower during Week 12 than those on Day 1, possibly due to autoinduction. Overt hepatotoxicity occurred at 100 mg/kg, whereas hepatic changes at 10 and 30 mg/kg were consistent with cytochrome P450 induction. The hepatic lesions were reversible within 4 weeks, while adrenal lesions were still evident after 4 weeks without treatment.

Cardiac hypertrophy in rats after intravenous administration of CI-959, a novel antiinflammatory compound: morphologic features and pharmacokinetic and pharmacodynamic mechanisms.

CI-959 is an antiallergic/antiinflammatory agent currently in development. In rats, daily bolus intravenous administration of CI-959 at doses > or = 10 mg/kg was associated with development of cardiac hypertrophy. There was no morphologic or biochemical evidence of myocyte injury, and cardiac hypertrophy rapidly reversed after treatment was discontinued. Cardiac hypertrophy was not evident when CI-959 was given orally or by continuous intravenous infusion with ALZA osmotic pumps. Maximum plasma drug concentrations (Cmax) were significantly higher when CI-959 was given by bolus intravenous injection, suggesting that cardiac effects were dependent on high Cmax concentrations. When neonatal rat cardiomyocytes were exposed to CI-959 in vitro, there was no evidence of myocyte enlargement or increased protein content. Cardiac hypertrophy was prevented by pretreatment with nonselective beta- and beta 1-selective adrenoceptor blockers as well as with central sympatholytics. beta 2- and alpha-adrenoceptor blockers were ineffective in preventing cardiac hypertrophy. Bolus intravenous CI-959 administration resulted in prolonged hypotension and associated increase in plasma catecholamine levels, with apparent inhibition of reflex tachycardia. We conclude that CI-959-associated cardiac hypertrophy in rats was not a direct drug effect but instead was probably mediated by endogenous catecholaminergic stimulation of cardiac beta 1-adrenoceptors.

Attenuation of avian infectious bronchitis virus by cold-adaptation.

Avian infectious bronchitis virus (IBV) Arkansas-type DPI strain was passaged 10 times in specific-pathogen-free (SPF) chicken embryos incubated at 28 C and 37 C. Virus grown at 28 C acquired cold-adapted (CA) and temperature-sensitive (TS) characteristics based on more-rapid growth at 28 C and a reduced ability to grown at 41 C, respectively, compared with non-cold-adapted (non-CA) virus grown at 37 C. The pathogenicity and immunogenicity were determined for CA and non-CA IBV in 1-day-old SPF chickens following intratracheal inoculation. The percentage of CA IBV-vaccinated chicks exhibiting respiratory disease exceeded 30% on only 1 day postinoculation (PI) (day 5 PI), compared with 8 days (days 2-9 PI) for birds given non-CA IBV. Mortality was 0% for CA IBV-vaccinated chickens and 6% for non-CA virus-vaccinated chickens. Microscopically, both CA and non-CA IBV caused diffuse tracheal deciliation, although mucosal hyperplasia, necrosis, and heterophil infiltration were more severe with non-CA IBV. Virus was reisolated from kidneys of chickens given CA IBV, suggesting the loss of the TS property. The instability of the TS property was confirmed by growth of the reisolated virus at 41 C. Both CA and non-CA viruses induced complete protection against homologous challenge virus infection of the upper respiratory tract.

Acute cardiovascular toxicity induced by an adenosine agonist-antihypertensive in beagles.

An adenosine agonist, designated chemically as (R)-N-(2,3-dihydro-1H-inden- 1-yl) adenosine, or CI-947, was administered to 3 male and 3 female beagles in oral doses of 5 mg/kg body weight. Multiple episodes of arrhythmia were recorded electrocardiographically with Holter monitors in 2 males and 2 females monitored up to 48 hr. One male and 1 female were necropsied at 24 hr and the remaining dogs were necropsied at 48 hr post-dosing. At 48 hr, multifocal perivascular epicardial and myocardial hemorrhage was noted grossly in 1 female. Microscopic coronary arterial alterations were present in all treated dogs irrespective of the occurrence of arrhythmias. At 24 hr, proteinic material and red cells were present in the media accompanied by minimal adventitial accumulation of neutrophils. At 48 hr, coronary arterial lesions progressed to media vacuolation, transmural necrosis, and perivascular accumulation of neutrophils. Ultrastructural alterations included: endothelial retraction, subendothelial accumulation of fibrin and platelets, necrosis of smooth muscle cells, and mural infiltration of granulocytes and monocytes. Coronary vascular injury may be due to altered hemodynamics associated with the coronary vasodilator properties of adenosine agonist compounds.

Ultrastructural juxtaglomerular cell changes in normotensive rats treated with quinapril, an inhibitor of angiotensin-converting enzyme.

Sequential histologic and ultrastructural changes in juxtaglomerular apparatus (JGA) were defined in male rats treated with quinapril, an inhibitor of angiotensin-converting enzyme (ACE). Doses of 0, 10, 100, and 400 mg/kg were administered daily by gavage for up to 4 weeks. Granular juxtaglomerular (JG) cells were normal or hypogranular on Day 1 at all doses and were hypergranular by Day 7 in rats given 100 and 400 mg/kg relative to age-matched controls. Histologically, JGA hypertrophy was apparent by Day 7 at all doses and was most pronounced by Day 14 in intermediate and deep cortical zones of rats given 100 and 400 mg/kg. Ultrastructurally, hypertrophic JG cells had abundant rough endoplasmic reticulum and free ribosomes, and prominent Golgi complexes associated with numerous cytoplasmic coated vesicles. Dose-dependent increases in numbers of protogranules, altered granules, and cytoplasmic vacuoles occurred in association with decreased size and increased pleomorphism of mature secretory granules. Granule alterations included vesicular to lamellar membranous matrical inclusions, irregular patterns of osmiophilia, matrical vacuolation, and flocculent to coarsely granular matrix of greater density than mature granules. We concluded that JG cell hypertrophy and hyperplasia occurred rapidly in response to subchronic ACE inhibition. Further, ultrastructural changes in JG cells were indicative of stimulated renin synthesis by a regulated pathway, renin secretion by exocytosis and cytoplasmic solubilization of granules, and autophagy of granules as a mechanism whereby JG cells regulate levels of stored renin under conditions of excessive stimulation.

Comparative pathogenesis of serotype 1 and variant serotype 1 isolates of infectious bursal disease virus and their effect on humoral and cellular immune competence of specific-pathogen-free chickens.

Specific-pathogen-free chickens inoculated with isolate VA (variant A) or isolate IM of infectious bursal disease virus (IBDV) were examined for mitogenic response to T-cell mitogens, primary and secondary antibody response to sheep erythrocytes and Brucella abortus, and gross and histologic lesions in thymus and bursa. Both isolates induced comparable depression in the mitogenic and antibody response, and both caused extensive gross and histologic lesions in the bursa of Fabricius. However, bursal necrosis induced by the IM isolate was accompanied by an inflammatory response, whereas the inflammatory component was lacking in the lesion induced by the VA isolate. Furthermore, the IM isolate induced extensive lesions in the thymus, but the VA isolate did not.

Plasma cell quantitation in the gland of Harder during infectious bursal disease virus infection of 3-week-old broiler chickens.

Histopathologic changes in the gland of Harder (GH) and bursa of Fabricius (BF) were studied during and after infection of 3-week-old broiler chickens with a pathogenic strain of infectious bursal disease virus (IBDV). Plasma cell (PC) necrosis in the GH was seen from 5 to 14 days postinoculation (PI), BF follicular necrosis was observed from 1 to 7 days PI. PC numbers within the GH, counted for 28 days after inoculation, declined and were reduced (P less than 0.01) by 51% at 7 days after inoculation, which coincided with PC necrosis and heterophil infiltration. After 14 days PI, however, PC numbers were equal to those in uninfected controls. Since the GH is a major antibody-producing site in the paraocular area, the reduction in PC number at 7 days PI might indicate compromise of local immunity in the paraocular region and upper respiratory tract associated with IBD.

Thoracic vertebral osteochondroma in a cat.

A thoracic vertebral (T5) osteochondroma was discovered in a 1 1/2-year-old male blue Persian cat with a history of acute hind limb paresis. Myelography revealed a mass on the dorsal surface of the vertebral body, which resulted in dorsal compression of the spinal cord. A dorsal laminectomy was performed, and the mass was rongeured entirely from the vertebral body. Although the cat's progress was initially slow after surgery, its neurologic status was assessed to be near normal, 15 months later.

Adrenocorticotropin-containing neoplastic cells in a pars intermedia adenoma in a horse.

Pituitary-dependent hyperadrenocorticism was diagnosed in a 14-year-old Arabian mare with chronic weight loss, hirsutism, polyuria, and polydipsia. The mare had a stress leukogram, glucosuria, and consistent hyperglycemia. Plasma glucose concentrations were resistant to suppression by insulin. Plasma cortisol concentrations were within normal limits, but did not respond to dexamethasone suppression and had an exaggerated response to ACTH stimulation. At necropsy, a chromophobe adenoma of the pars intermedia of the pituitary gland was found. The zona fasciculata of the adrenal cortex and the pancreatic islets of Langerhans were hypertrophied. An immunohistologic staining technique was used to demonstrate ACTH-containing neoplastic cells in the pituitary mass. These cells released ACTH and other peptides that initiated the chain of endocrinologic events leading to clinical disease.

Phosphorus availability bioassay using bone ash and bone densitometry as response criteria.

Two experiments were conducted to examine the relative precision of bone densitometry and bone ash methodologies as response criteria in measurement of bioavailability of phosphorus from various supplements for turkeys. Multivariate analyses of variance were used to analyze data collected. Coefficients of correlation and variation and F ratios were used for evaluation. Bone densitometry with one scan at each of 3 points on the bone was faster than bone ash and as precise as bone ash analysis in measuring phosphorus availability in turkeys. The coefficient of correlation between percentage ash (of dry bone) and scan density (milligrams per centimeter length of bone) measurements for treatment effects was .986. The coefficient of variation was about the same for the bone ash (5.8) and the three-point bone scan (6.9) methods. As indicated by the F ratio for testing treatment effects, bone densitometry was better able to detect differences among phosphorus sources. A technician may scan 50 cleaned bones in 3 hr, but with the bone ash method, drying, ashing, and weighing may require 3 working days. Bone sampling technique, multiple operators, different bone sizes, and decay of iodine source were the major factors affecting precision of the bone densitometry technique. Relative biological availabilities of phosphorus from various supplements were about the same by the two methods.

Malignant hyperthermia susceptibility: cardiac histomorphometry of dogs and young and market-weight swine.

The defect causing malignant hyperthermia has been proposed to involve cardiac as well as skeletal muscle. We tested the hypothesis that histomorphometric parameters for ventricular wall from malignant hyperthermia-susceptible swine and dogs were abnormal. Hearts were obtained from: mature dogs, age- and weight-matched young swine (89 +/- 15 days, 30 +/- 3 kg); and market-weight swine (102 +/- 10 kg). Using light microscopy, estimates were made for muscle nuclear dimensions and the volume-fraction of nuclei, sarcoplasm, blood vessels, and interstitial space. Cardiac maturation in both MH and normal swine was accompanied by decreased myocyte volume-fraction due to decreased nuclear volume-fraction and increased interstitial space volume-fraction. Sarcoplasm and vasculature volume-fraction were unchanged after maturation. Nuclear volume-fraction was slightly greater (p less than 0.05) in the right ventricle than the left for malignant hyperthermia and normal swine. Myocyte nuclear dimensions were generally similar among animals. Dogs and the oldest group of swine were not significantly different. Myocytes of all swine contained multiple nuclei, closely spaced in rows of 2 to 12. In contrast, most myocytes of mature dogs apparently contained one or two nuclei. Histomorphometric values were not significantly different between normal and malignant hyperthermia young swine and dogs. However, within the market-weight swine, volume-fraction for malignant hyperthermia myocytes and myocyte nuclei was decreased and interstitial space was increased compared to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myelomonocytic leukemia with neurologic manifestations in the dog.

A dog was presented with mandibular paralysis, photophobia, and diffuse atrophy of the cranial skeletal muscles. Physical examination also revealed glossal paralysis, reduction of the swallowing reflex, reduction of the pupillary light response, and generalized lymphadenopathy. Cytologic and ultrastructural examinations of blood films, bone marrow, and lymph node aspirates were consistent with acute myelomonocytic leukemia. Post-mortem examination revealed extensive, multisystemic neoplastic infiltration with marked involvement of the central and peripheral nervous systems, especially the cranial and lumbar spinal nerves and associated ganglia. Neurologic manifestations are unusual in acute myelomonocytic leukemia in the dog.

Venereal pox in breeder turkeys in Minnesota.

Venereal pox was identified in four flocks of breeder turkeys following semen collection and artificial insemination. Proliferative fungate lesions were confined to the vent, cloaca, and, rarely, the oviduct. It was concluded that semen collection and artificial insemination may facilitate mechanical transmission of poxvirus.