Caprine mucopolysaccharidosis-IIID: clinical, biochemical, morphological and immunohistochemical characteristics.

Several animal models have been developed for the mucopolysaccharidoses (MPSs), a group of lysosomal storage disorders caused by lysosomal hydrolase deficiencies that disrupt the catabolism of glycosaminoglycans (GAG). Among the MPS, the MPS-III (Sanfilippo) syndromes lacked an animal counterpart until recently. In this investigation of caprine MPS-IIID, the clinical, biochemical, morphological, and immunohistochemical studies revealed severe and mild phenotypes like those observed in human MPS III syndromes. Both forms of caprine MPS IIID result from a nonsense mutation and consequent deficiency of lysosomal N-acetylglucosamine 6-sulfatase (G6S) activity and are associated with tissue storage and urinary excretion of heparan sulfate (HS). Using special stains, immunohistochemistry, and electron microscopy, secondary lysosomes filled with GAG were identified in most tissues from affected goats. Primary neuronal accumulation of HS and the secondary storage of gangliosides were observed in the central nervous system (CNS) of these animals. In addition, morphological changes in the CNS such as neuritic expansions and other neuronal alterations that may have functional significance were also seen. The spectrum of lesions was greater in the severe form of caprine MPS IIID and included mild cartilaginous, bony, and corneal lesions. The more pronounced neurological deficits in the severe form were partly related to a greater extent of CNS dysmyelination. These findings demonstrate that caprine MPS IIID is a suitable animal model for the investigation of therapeutic strategies for MPS III syndromes.

Pathology of 6-aminonicotinamide toxicosis in the rabbit.

Daily doses of 6-aminonicotinamide (3-5 mg/kg) given by ip injection produced ataxia of the hind limbs progressing to an ascending paresis/paralysis, anorexia, diarrhoea and death in male and female New Zealand White and Dutch Belted rabbits. At autopsy, caecal and gastric distention were seen and the apex of the gall bladder had necrotic foci. Light microscopic lesions included atrophy and necrosis of the white lobe of Harder's gland and atrophy of seminiferous tubules with cellular necrosis, vacuolation and the presence of multinucleated giant cells. Cytoplasmic vacuolation was observed in epithelial cells from many tissues, usually in the basal portion of the cells. Vacuolation of the epithelium of the sacculus rotundus and vermiform appendix was found within the same time frame as histiocytic hyperplasia in these organs. Spongiosis and gliosis were seen in certain parts of the central nervous system. Ultrastructural alterations in the gall bladder epithelium consisted of distention of intercellular space, mild distention of perinuclear space and coalescing, intracytoplasmic, membrane-bound vacuoles, a few of which contained membranous debris. Some alterations of 6-aminonicotinamide toxicosis were prevented by simultaneous administration of nicotinamide with 6-aminonicotinamide.

Multigenerational study of the effects of consumption of PCB-contaminated carp from Saginaw Bay, Lake Huron, on mink. 1. Effects on mink reproduction, kit growth and survival, and selected biological parameters.

This study was conducted to determine the multigenerational effects of consumption of PCB-contaminated carp (Cyprinus carpio) from Saginaw Bay (Lake Huron) on mink (Mustela vison) reproduction and health and to examine selected biomarkers as potential indicators of polyhalogenated hydrocarbon toxicity in mink. The mink were fed diets formulated to provide 0 (control), 0.25, 0.5, or 1.0 ppm polychlorinated biphenyls (PCBs) through substitution of Saginaw Bay carp for ocean fish in the diets. To determine whether the effects of PCB exposure were permanent, half of the parental (P1) animals were switched from their respective treatment diets to the control diet after whelping the first of two F1 generations. Effects of in utero and lactational exposure to PCBs on subsequent reproductive performance of the F1 animals were examined by switching half of the first-year F1 offspring (kits) to the control diet at weaning, while the other half was continued on their parental diet (continuous exposure). Continuous exposure to 0.25 ppm, or more, of PCBs delayed the onset of estrus (as determined by vulvar swelling and time of mating) and lessened the whelping rate. Litters whelped by females continually exposed to 0.5 ppm, or more, of PCBs had greater mortality and lesser body weights than controls. Continuous exposure to 1.0 ppm PCBs had a variable effect on serum T4 and T3 concentrations. Compared to the controls, there were significant differences in kidney, liver, brain, spleen, heart, and thyroid gland weights of the mink continually exposed to 1.0 ppm PCBs. There was an increase in the incidence of periportal and diffuse vacuolar hepatocellular lipidosis in the P1 mink with continuous exposure to increasing concentrations of PCBs. Plasma and liver PCB concentrations of the adult and kit mink were, in general, directly related to the dietary concentration of PCBs and the duration and time of exposure. Short-term parental exposure to PCBs had detrimental effects on survival of subsequent generations of mink conceived months after the parents were placed on "clean" feed. The lowest observed adverse effect level (LOAEL) for dietary PCBs in this study was 0.25 ppm.

Proliferation of maxillary and mandibular periodontal squamous cells in mink fed 3,3',4,4',5-pentachlorobiphenyl (PCB 126).

This report characterizes squamous cell proliferation in young farm mink (Mustela vison) fed a diet supplemented with 0.024 ppm 3,3',4,4',5-pentachlorobiphenyl (polychlorinated biphenyl [PCB] congener 126). One to 2 months of dietary exposure to PCB 126 resulted in gross lesions of the upper and lower jaws consisting of mandibular and maxillary nodular proliferation of the gingiva and loose teeth. The maxilla and mandible of the PCB-treated mink were markedly porous because of loss of alveolar bone. Histologically, this osteoporosis was caused by proliferation of squamous cells that formed infiltrating cords. This report clearly documents the fact that the environmental contaminant PCB 126 can cause osteoinvasive squamous proliferation in young mink, although the dose used in the present study was 7 and 36 times higher than what is typically encountered in contaminated bird eggs and fish, respectively.

Otitis media in preweaned Holstein dairy calves in Michigan due to Mycoplasma bovis.

Mycoplasma bovis was isolated from the tympanic bullae of dairy calves with an exudative otitis media. The history, clinical signs, gross and histologic lesions, and bacteriologic findings are described for 5 preweaned Holstein calves with otitis media from a 600-cow dairy in Michigan. Clinical findings consisted of unilateral or bilateral ear droop, epiphora, head tilt, and recumbency in severely affected calves. Postmortem examination revealed unilateral or bilateral fibrinosuppurative to caseous exudate in the tympanic bullae. Histologically, a marked fibrinosuppurative to caseous exudate filled the tympanic air spaces. The partially ulcerated tympanic mucosa was markedly thickened with mononuclear cell infiltration and proliferation of fibrous connective tissue. Bone remodeling and periosteal hyperostosis were present in some osseous septa. Mycoplasma bovis was isolated from the tympanic bullae of all 5 calves and from the lungs of 2 calves and the frontal sinus of 1 calf. Mycoplasma bovis was isolated at > 100,000 colony forming units/ml from the bulk milk tank of the farm of origin. The isolation of M. bovis from the bulk milk tank, indicating subclinical mycoplasmal mastitis coupled with the feeding of waste milk from mastitic cows to calves is suggestive of a possible source of the infection resulting in otitis media in preweaned dairy calves.

Ocular and encephalic toxoplasmosis in canaries.

In this report we describe the lesions produced by the protozoal organism, Toxoplasma gondii, in the eyes and brain of the common yellow canary (Serinus canaria). Nine of 15 birds in a flock were affected with blindness, which developed over a 3-mo span, and two birds developed torticollis. Microscopic alterations within the eye consisted of a nonsuppurative chorioretinitis with large numbers of macrophages that contained the tachyzoite form of T. gondii in the subretinal space, and aggregates of tachyzoites were found in the nerve fiber layer of the retina with and without necrosis. Tissue cysts with bradyzoites were scattered throughout the meninges and neuropil of the cerebrum and cerebellum. Both forms were confirmed by transmission electron microscopy in the eye and brain. Frozen brain samples reacted with T. gondii-specific cat sera in indirect fluorescent antibody tests. The source of infection was hypothesized to be from a stray cat the owner kept that had access to some of the bird feed. Treatment (trimethoprim 0.08 g/ml H2O and sulfadiazine 0.04 g/ml in water for 2 wk) was instituted by the referring veterinarian on the remaining birds. A second treatment regime was given for 3 wk. The owner of the canaries did not return for further treatment.

Cataracts and crooked toes in Brahma chickens.

In 1991, 69% of the cockerels and 15% of the pullets in an inbred flock of approximately 200 dark and light Brahma chickens had unilateral or bilateral cataracts and crooked toes. Affected chickens were normal at hatching but developed cataracts with or without crooked toes by 6 months of age. The cataracts were initially focal and polar but progressed to be diffuse throughout the lenticular cortex. The crooked toes involved one or more of the second, third, and fourth digits and were due to a medial deviation of the distal aspect of the first phalanx. The cataracts and crooked toes were considered likely due to a hereditary defect, based on the following: the history of flock inbreeding; the lack of historical, clinical, or pathological evidence of avian encephalomyelitis or Marek's disease; the presence of lesions only in Brahma chickens and not in the approximately 200 other chickens on the farm kept under the same management and environmental conditions; the age at which the lesions occurred; and the nature of the lesions.

Fatal cysticercosis by Taenia crassiceps (Cyclophyllidea: Taeniidae) in a presumed immunocompromised canine host.

Cysticercosis in a canine host (Canis familiaris) attributable to the taeniid cestode Taenia crassiceps is reported for the first time in North America. Numerous parent and daughter cysticerci occurred in a massive intrapleural and intraperitoneal infection in an apparently immunocompromised host. The largest cysticerci were ovoid to elongate, 5-9 mm in maximum length, and armed with 32-34 rostellar hooks in 2 rows; small hooks measured 114-143 microm long (x = 124+/-8.2 microm), and large hooks were 156-180 microm (x = 163+/-7.4 microm). Taenia crassiceps is widespread in boreal North America and, like a number of other taeniids, constitutes a potential risk as a zoonotic parasite. The immunological status of the host may be important in determining the outcome of infections for this and other taeniids in atypical hosts.

Congenital ocular abnormalities of Rocky Mountain Horses.

OBJECTIVE: To determine the incidence and describe ocular abnormalities in a cross-section of the population of Rocky Mountain Horses. Design: Prospective study. Animals: Five-hundred and fourteen Rocky Mountain Horses. Procedure: Ophthalmic examinations were performed using a slit-lamp biomicroscope and an indirect ophthalmoscope. Intraocular pressures were measured by applanation tonometry. Eyes from six horses were obtained for histologic examination. RESULTS: Cysts of the posterior iris, ciliary body, and peripheral retina were detected most frequently (249 horses), and were always located temporally. Curvilinear streaks of retinal pigmented epithelium extending from the peripheral temporal retina marked the boundary of previous retinal detachment in 189 horses. Retinal dysplasia was detected in 125 horses. Multiple ocular anomalies were evident in 71 horses and were always bilateral and symmetrical. Affected eyes had a large, clear cornea that protruded excessively and had an apparent short radius of curvature, a deep anterior chamber, miotic and dyscoric pupil, and iris hypoplasia. Pupillary light responses were decreased or absent and pupils failed to dilate after repeated instillation of mydriatic drugs in horses with multiple ocular anomalies. Less frequently encountered abnormalities included peripheral iridocorneal adhesions and goniosynechiae. Congenital cataract was always present in eyes with multiple abnormalities. Intraocular pressures did not differ among horses with normal eyes and horses with multiple ocular abnormalities. Histologic examination of eyes corroborated the clinical appearance.

Use of nested polymerase chain reaction (PCR) for detection of retroviruses from formalin-fixed, paraffin-embedded uveal melanomas in cats.

Thirty-six formalin-fixed, paraffin-embedded enucleated globes from cats with a diagnosis of diffuse anterior uveal melanoma were obtained. Sections of tumor were excised, deparaffinized, and subjected to nested polymerase chain reaction (PCR) to identify proviral DNA sequences from the feline leukemia virus (FeLV)-feline sarcoma virus (FeSV; 36 eyes), and the feline immunodeficiency virus (FIV; 18 eyes). All samples tested were negative for FIV DNA. Three samples were positive for FeLV-FeSV DNA. This is the first reported evidence of a possible link between naturally occurring feline anterior uveal melanoma and the presence of FeLV-FeSV DNA.

Mast cell numbers in normal and glaucomatous canine eyes.

Numbers of mast cells in the cornea, sclera, choroid, ciliary body, iris, and retina of sections of globes from 35 clinically normal dogs and 34 dogs with secondary glaucoma was determined. Fixed globes were trimmed along a vertical midsagittal plane and embedded in paraffin. Tissue sections, approximately 6 microns thick, were stained with toluidine blue for identification of mast cells. In normal globes, most of the mast cells were observed in the anterior portion of the uvea, and fewer mast cells were seen in the choroid and sclera. Mast cells were not observed in the retina and were seldom observed in the cornea of dogs with or without glaucoma. In sections of glaucomatous globes, mast cells were distributed evenly in the uvea and sclera, and fewer mast cells were present than in normal globes, regardless of the cause of glaucoma.

Influence of exogenous hyaluronan on synthesis of hyaluronan and collagenase by equine synoviocytes.

OBJECTIVE: To evaluate the influence of exogenous hyaluronan (HA) on in vitro synthesis of HA and collagenase by equine synoviocytes from normal and inflamed joints. ANIMALS: 9 adult horses. PROCEDURE: Synoviocytes for culture were taken from the middle carpal joint of 3 horses with normal joints (control) and 6 horses with osteochondral fractures (principal). Synoviocytes were propagated in monolayer cultures and were incubated with 3 commercial HA products at concentrations of 0, 200, 400, and 1,500 micrograms/ml. Newly synthesized HA was radiolabeled with [3H]glucosamine and quantified by cetylpyridinium chloride precipitation and liquid scintillation counting. The hydrodynamic size of radioactive HA was determined by high-performance liquid chromatography, and collagenase activity was evaluated by use of a quantitative radioactive collagen film assay. RESULTS: Exogenous HA influenced neither the rate of synthesis nor the hydrodynamic size of the newly produced HA by control or principal cell cultures. Culture supernatants from abnormal synovium, exposed to 400 and 1,500 micrograms of exogenous HA/ml, contained significantly more collagenase activity than did those exposed to lower concentrations. CONCLUSION: Although HA is thought to have beneficial effects in equine arthropathies, the principal mechanisms of action of HA do not appear to be stimulation of synthesis of HA of augmented molecular weight or marked inhibition of collagenase synthesis.

Ocular, naso-maxillary, and neural anomalies in raccoons, Procyon lotor (L.).

Congenital ocular and related anomalies were studied in two unrelated young raccoons. One animal was anophthalmic and had severe anomalies of the central nervous system, consisting of meningoencephalocele, pachygyria, hydranencephaly, cerebellar cavitation, syringomyelia, and other defects. A second animal was microphthalmic with congenital defects of the nose, maxilla and teeth. Ocular lesions were severe and included chorioretinal coloboma, retinal folds, disorganized neuroectodermal cell layers, spherophakia, cataract and other defects. The nose had unilateral abnormal epithelium, hair follicles, sweat glands and sebaceous glands, and a lack of parietal cartilage on the affected side.

Pharyngeal polyps in two feline siblings.

Pharyngeal polyps were diagnosed in 2 sibling kittens referred for evaluation of chronic upper respiratory tract disease. Surgical excision of the masses was performed in both kittens after skull radiography and oral examination. One kitten had a recurrence of pharyngeal polyps 5 weeks after surgery and was euthanatized and necropsied. The clinical and histologic findings in these 2 cases suggested a congenital origin of this disease.

Anterior uveal melanoma, with secondary keratitis, cataract, and glaucoma, in a horse.

Intraocular melanoma was diagnosed in a 13-year-old horse. Secondary clinical findings included keratitis, cataract, and glaucoma. The eye was enucleated. Follow-up information did not give an indication of metastatic disease.

Cerebrospinal nematodiasis and visceral larva migrans in an Australian (Latham's) brush turkey.

Cerebrospinal nematodiasis and visceral larva migrans were diagnosed in an Australian (Latham's) brush turkey (Alectura lathami) that died at the Indianapolis Zoo following a progressive neurologic disease. Histologically, multifocal areas of malacia, necrosis, and inflammation were seen in sections of cerebrum, cerebellum, and midbrain; lesions were most severe in the cerebellum. A large granuloma in a lung contained cross sections of a large ascarid larva identified as Baylisascaris. The CNS lesions were typical of larval migration, as documented in other avian species. An epizootiologic investigation indicated that Baylisascaris procyonis was the etiologic agent and that the bird had acquired the parasite through contact with fecal contamination from wild raccoons at the St Louis Zoo, where the bird had been raised.

Intraocular findings in three dogs and one cat with chronic glaucoma.

Intraocular neoplasia may cause secondary glaucoma. If an intraocular prosthesis is placed in an eye with glaucoma secondary to intraocular neoplasia, the neoplasm frequently regrows around the prosthetic ball, resulting in recurrence of buphthalmos and signs of pain. Histologic examination of eviscerated intraocular contents of 4 animals resulted in diagnosis of intraocular neoplasia in 2 glaucomatous eyes and ruled out neoplasia as the cause of glaucoma in 2 eyes.

Giant cell tumor of soft parts in six horses.

Giant cell tumor of soft parts was diagnosed in 6 horses 3 to 12 years old (mean, 6.8 +/- 3.5 years): 3 Quarter Horse geldings, 2 Standardbred mares, and 1 Standardbred stallion. The neoplasms developed as raised, solitary masses, approximately 1 to 4 cm in diameter, which were firmly attached to subcutaneous tissue of the neck (1 horse), shoulder (1 horse), thigh (2 horses), or stifle (2 horses). Excision was followed by local recurrence in 3 horses within 1 to 1 1/2 months. The neoplasms were firm and cut with resistance. On cut surface, they were white, with mottled red hemorrhagic areas.

Glaucoma associated with a high number of mast cells in the uveal tract of an African lion cub.

An 8-week-old male lion cub (Panthera leo) was referred for evaluation of an enlarged and reddened left eye. Ocular examination revealed a buphthalmic left globe, with corneal edema, superficial neovascularization, moderate episcleral injection, a fixed dilated pupil, and an intraocular pressure of greater than 41.5 mm of Hg as measured by the Schiotz tonometer and a human conversion chart. A diagnosis of glaucoma was made. A silicone prosthesis was implanted after evisceration of the intraocular contents. Histologic examination of the eviscerated uveal tissue revealed numerous congested and dilated vessels of various sizes. Neutrophils were marginated along the vascular endothelium, and the uveal stroma was infiltrated by a few lymphocytes and numbers (3 to 30/hpf) of widely disseminated, well-differentiated mast cells with abundant, well-granulated cytoplasm.