GM2 ganglioside lysosomal storage disease in cats with beta-hexosaminidase deficiency.

Two kitteens with progressive neurologic disease had increased concentrations of GM2 ganglioside in their cerebral cortex. Examination under the light microscope revealed cytoplasmic vacuolation of neurons and hepatocytes. Transmission and scanning electron microscopy demosntrated cytoplasmic inclusions encompassed by membranes in various central nervous system cell types and in hepatocytes. Beta-D-N-acetyl-hexosaminidase activity was reduced to about 1.0 percent of normal in brain, liver, and cultured skin fibroblasts of the diseased kittens; both major electrophoretic forms, A and B, of the enzyme were deficient. In fibroblasts from the parents of the diseased kittens, this enzyme activity was intermediate between that of affected and normal cats, suggesting an autosomal recessive mode of inheritance of the enzyme defect. Histopahtological and ultrastructural lesions, glycolipid storage, enzyme defect, and pattern of inheritance are similar to those of human GM2 gangliosidosis type 2.

Hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy is a newly recognized motor neuron disease occurring in Brittany Spaniels. The clinical manifestations, pattern of inheritance, electrodiagnostic findings, and muscle biopsies have features in common with human spinal muscular atrophy. Neuropathological examination discloses some loss of motor neurons in the spinal cord and brainstem. Many of the surviving motor neurons have neurofibrillary swellings in proximal axons, an abnormality similar to that which occurs early in the course of human amyotrophic lateral sclerosis. These axonal swellings are filled with maloriented skeins of neurofilaments. Since the proteins comprising neurofilaments are carried by slow axonal transport, their accumulation within axons suggest that the swellings may result from impaired slow transport, a hypothesis that can be tested in affected Brittany Spaniels. Hereditary canine spinal muscular atrophy is a new genetic, clinical, and pathological entity, and, at present, it appears to be the best currently available animal model of motor neuron disease.

Effects of prednisone on thyroid and gonadal endocrine function in dogs.

To assess the effect of a glucocorticoid on thyroid and gonadal endocrine function, prednisone was administered on alternate days to dogs. The prednisone injections resulted in adrenocortical suppression, as shown by the response to ACTH. Basal plasma thyroxine and tri-iodothyronine concentrations were considerably reduced in prednisone-treated dogs. However, the thyroid response to injection of thyrotrophin-releasing hormone was not altered, indirectly demonstrating that pituitary release of TSH was not inhibited by prednisone. Similarly, the response of the thyroid to exogenous TSH was not reduced by prednisone treatment. Electron microscopic examination of thyroid tissue revealed accumulation of colloid droplets in the follicular cell cytoplasm of dogs treated with prednisone. It is postulated that prednisone may interfere with basal thyroid hormone secretion by inhibiting lysosomal hydrolysis of colloid in the thyroid follicular cell. Basal plasma concentrations of LH and testosterone, measured in the male dogs, were reduced by prednisone treatment. Responses of prednisone-treated dogs to luteinizing hormone releasing hormone were not significantly reduced. Prednisone administration did not alter testicular responsiveness to injection of human chorionic gonadotrophin. After orchidectomy, plasma LH values were significantly reduced in prednisone-treated dogs. Taken together, these results suggest that LH secretion in dogs is inhibited at the hypothalamic and/or pituitary level by prednisone administration, which consequently results in reduced testosterone concentrations.

Cryptosporidiosis of the bursa of Fabricius of chickens.

Light-microscope and electron-microscope studies of a coccidial organism found in the bursa of Fabricius from 3 chickens clearly established the parasite as belonging to the family Cryptosporiidae. Hyperplasia and heterophil infiltration were associated with the presence of organisms attached to the microvillus border of epithelial cells lining the plicae of the bursa of Fabricius. Although there were no clinical signs or gross lesions common to the 3 cases described, all had similar histologic lesions in the epithelium lining the bursa of Fabricius.

Electron microscopy of selectively denervated canine carotid sinuses.

Selective denervation as used to characterize the nerve endings in the carotid sinus wall of the dog. Areas of dense innervation were identified by acetylcholinesterase histochemical technique and sampled for electron microscopic study following survival periods of 48 to 144 hours after selective neurectomies were done. Large varicosities, similar to previously described mechanoreceptor endings, showed signs of degeneration after transection of the sinus nerve, but not after cranial cervical ganglionectomy or section of the glossopharyngeal nerve proximal to its sensory ganglia. These were concluded to be endings of afferent neurons. Histochemical reactions at the fine structure level demonstrated such varicosities to be acetylcholinesterase positive. Smaller varicosities containing granulated synaptic vesicles degenerated after cranial cervical ganglionectomy was done. These were interpreted to be postganglionic sympathetic endings. This study represents an example where denervation, coupled with short survival periods, serves as a technique for studying selected areas of the peripheral nervous system.

Effect of humidification on the airways of cats during high-frequency ventilation.

The effect of humidity on the histologic lesions induced by high-frequency jet ventilation was investigated in 12 healthy cats. After 16 hours of ventilation, the appearance of the tracheal epithelium ranged from normal to necrotic. The damage was considerably more severe in the trachea of cats of the group ventilated without added humidity. Increasing the relative humidity to 63% at 24 C had a protective effect, but further increasing the relative humidity to 92% at 35 C did not appear to provide significantly more protection. The bronchi and distal airways had minimal, if any, damage in all groups.

Effects of vascular pedicle ligation on blood flow in canine semitendinosus muscle.

Blood flow to the semitendinosus muscle was studied in 12 dogs after ligation of either the proximal or distal vascular pedicle and elevation of the muscle from its normal position. Using 15-micron-diameter radioactive microspheres, flow was measured at rest, 6 and 18 days after muscle elevation and pedicle ligation. Mean blood flow in the proximal region of the muscle 6 and 18 days after ligation of the caudal gluteal (proximal) pedicle was not significantly different from mean blood flow calculated in the middle and distal regions of the muscle. There was also no significant difference in mean blood flow among proximal, middle, and distal regions of the muscle, 6 and 18 days after ligation of the distal caudal femoral (distal) pedicle. There was significantly (P < 0.05) increased blood flow between group-A (ligation of caudal gluteal artery) and group-C (operated-control) muscles, 6 and 18 days after surgery. There was no loss of muscle fiber striations or nuclei, or presence of fibrous tissue that might have indicated ischemic necrosis in any of the experimental groups. These results indicate that the entire semitendinosus muscle can be sustained by the blood flow from either of its 2 vascular pedicles, which reinforces its potential as a muscle flap.

Scanning electron microscopy of experimentally induced pyelonephritis in the rat.

Scanning electron microscopy was used to observe epithelial and inflammatory changes in kidneys of rats during Corynebacterium renale-induced experimental ascending pyelonephritis. Bacteria were not observed adhering to pelvic epithelium, although there was evidence of cell sloughing. Bacteria was observed in the interstitium of the renal medulla. Bacteria, when present in the tubular lumen, were associated with discontinuities in cell membranes. Phagocytic cells appeared in the interstitium and phagocytosis was evident in the renal medulla.

Effect of prednisone on thyroid gland morphology and plasma thyroxine and triiodothyronine concentrations in the dog.

The effects of multiple IM injections of prednisone (2.2 mg/kg) on thyroid morphology and on plasma thyroxine (T4) and triiodothyronine (T3) concentrations in dogs were determined, and the effects of a single prednisone injection on the same circulating iodothyronine concentrations were assessed. Plasma T4 and T3 concentrations decreased significantly after 3 injections of prednisone were made. However, with a single prednisone injection, there was no significant difference in plasma T4 values between control and treated animals. Starting at 8 hours after a single prednisone injection and continuing through day 2, plasma T3 values were significantly lowered. Prednisone treatment also resulted in significantly more thyroid cytoplasmic colloid droplets per follicular cell (3.19 vs 0.57 in treated and control dogs). Lysosomal hydrolysis of colloid appeared to be inhibited by glucocorticoids in dogs, resulting in an alteration of normal thyroid gland functioning.

Intimal lesions of the pulmonary artery in dogs with experimental dirofilariasis.

Microscopic examination, particularly by scanning electron microscopy, of the tunica intima of the pulmonary arteries of dogs experimentally infected with a known number of larvae of Dirofilaria immitis revealed various numbers and shapes of intimal thickenings. The number and morphology of these thickenings were related to the degree of infection. At 11 months after infection, dogs having adult worm populations of 8 to 21 worms had scattered discrete intimal lesions, whereas in dogs with 41 to 68 adult worms, the intima was diffusely affected. Discrete lesions took the form of rugous or verrucous protrusions, and in severely affected animals, the intima was extensively covered with anatomosing ridges. Light microscopy and transmission electron microscopy confirmed earlier reports that the thickenings were mainly confined to the tunica intima, that the surface was covered by endothelium, and that many of the cells in the intimal swellings were derived from smooth muscle.

Focal loss of pigment in the Belgian Tervuren dog.

Hypopigmentation most commonly affecting the face and mouth of the Belgian Tervuren dog was characterized by an absence of melanocytes in the epidermis. Pigment loss usually occurred during young adulthood, and although there was partial repigmentation in some dogs, complete repigmentation did not occur. Treatment with vitamin and mineral supplements was unrewarding. The condition appeared to have some degree of heritability and to be similar to vitiligo in man.

Disseminated protothecosis with central nervous system involvement in a dog.

A 4-year-old mixed-breed spayed bitch was euthanatized after 2 1/2 months of progressive neurologic disease. Prototheca organisms were identified by histopathology, culture, and electron microscopy. Specific fluorescent antibody procedures revealed two species--Prototheca wickerhamii and Prototheca zopfii. Organisms and pyogranulomatous lesions were found in the brain, spinal cord, right eye, kidneys, and heart.

Myopathy associated with hyperadrenocorticism in the dog.

Naturally occurring or iatrogenic hyperadrenocorticism was associated with myopathy in six dogs. One dog had muscle weakness and muscle atrophy but normal electromyographic findings. Five dogs had muscle stiffness, proximal appendicular muscle enlargement, and myotonic discharges on electromyography. Histologic, electron microscopic, and histochemical findings in the musculature of dogs that were examined were characteristic of noninflammatory degenerative myopathy. Clinical signs of the myopathy improved to varying degrees in five dogs that were treated for the hyperadrenocorticism.

Exocytosis of residual bodies in a lysosomal storage disease.

Scanning and transmission electron-microscopic study of the livers of 2 kittens suffering from GM2 gangliosidosis revealed discontinuities in the plasma membrane of hepatocytes and Kupffer cells, indicating an attempt by the cells to free themselves of excess lysosomal residues by means of exocytosis. Inclusions morphologically similar to those seen in the hepatocytes were observed in the perisinusoidal space. Openings were seen on all surfaces of the hepatocytes. Such extrusion of lysosomal residues is an example of a mechanism rarely observed in viable metazoan cells.

The pathology of feline GM2 gangliosidosis.

An 11-week-old and a 6-month-old kitten with feline GM2 gangliosidosis and deficiency in both A and B isoenzymes of beta-D-N-acetyl hexosaminidase were studied by light transmission (TEM), and scanning electron microscopy (SEM). Neurons throughout the nervous system contained cytoplasmic, membrane-bound inclusions which were PAS-positive at the fine structure level these inclusions were composed of membranous arrays in whorls, vesicles, or multilaminated stacks. Fusion of the bounding membranes of adjacent inclusions resulted in large inclusion-containing vacuoles. Hepatocytes and Kupffer cells contained inclusions slightly different from those in the central nervous system. SEM of cryofractured liver demonstrated their coalescence to form larger composite vacuoles. Vacuoles with inclusions were also seen in pancreatic acinar cells, endothelial cells, vascular smooth muscle, fibroblasts, myocardial cells, renal interstitial cells, corneal stromal cells, and R-E cells of bone marrow and spleen. The specific granules of eosinophils were swollen and took on bizarre forms. Pathologic manifestations of feline GM2 gangliosidosis differ from those seen in feline GM1 gangliosidosis but closely resemble those of Sandhoff disease in humans.