A splice-site mutation causing ovine McArdle's disease.

McArdle's disease is an autosomal recessive myopathy with symptoms of exercise intolerance caused by deficiency of the enzyme muscle glycogen phosphorylase which releases glucose for contraction during exercise. The human cDNA has been sequenced and disease-causing mutations identified. An ovine equivalent of McArdle's disease has been diagnosed and the mutation responsible identified by PCR-amplification of the ovine glycogen myophosphorylase cDNA in six overlapping fragments followed by single strand conformation polymorphism (SSCP) analysis. Two fragments showed SSCPs in the glycogen myophosphorylase cDNA from affected sheep. The SSCP in fragment one was a silent polymorphism, while that in fragment six, was an eight base deletion at the 5' end of exon 20. This deletion will cause a frame-shift, a premature stop codon and remove the last 31 amino-acid residues from the protein. The cDNA deletion suggested that the genomic mutation most likely involved a splice-site. Sequencing intron 19 identified the mutation as an adenine for guanine substitution at the intron 19 3' splice-site. This eliminated an XbaI site present in normal sheep allowing diagnosis of normal, affected and carrier sheep. This ovine model of McArdle's disease is now available for therapeutic trials.

Induction of diabetes in PVG/c strain rats by manipulation of the immune system.

A combination of thymectomy and sublethal irradiation (Tx-X) consistently induced diabetes in female rats of the PVG/c strain. The incidence of diabetes varied from 10.7% to 53.4% in seven successive Tx-X groups (mean 29.7%). Both clinical and subclinical disease was observed with the majority of affected animals developing the former condition. This was acute in onset, rapidly fatal (1-4 days) and characterized by ketosis and lipidemia. Overtly diabetic rats had markedly raised plasma glucose concentrations compared to normal rats of the same strain and plasma immunoreactive insulin concentrations were correspondingly depressed in this group. Histopathological change within the islets of Langerhans correlated with clinical status and ranged from diffuse atrophy in the majority of the acutely diabetic rats to mild and focal lymphocytic insulitis in a proportion of the non-diabetic rats. Islet cell autoantibodies were demonstrated by indirect immunofluorescence in approximately 25% of clinically diabetic animals. The majority of diabetic rats were found to be responsive to insulin and the clinical signs could be reversed by daily parenteral insulin administration. These observations implicate the immune system in diabetes generation and are consistent with an immune mediated pathogenesis as the underlying cause of the islet cell destruction. This syndrome may thus be a potentially useful animal model for type 1 (insulin dependent) diabetes in man.

Swainsonine toxicosis suppresses appetite and retards growth in weanling rats.

Two groups of weanling rats were treated with swainsonine, the toxin responsible for 'pea-struck' and locoism in grazing animals, for 21 days. The initial dose rate was 46 mg kg-1 d-1 in one group, and 7.6 mg kg-1 d-1 in the other. Food and water intake, urinary volume and bodyweight gain were recorded for each rat and compared with those for pair-fed and ad libitum fed control individuals. At both dose rates, swainsonine caused marked retardation of growth consequent to profound suppression of appetite. In intoxicated rats, intake of water was also diminished.

Immunohistochemical demonstration of canine distemper virus antigen as an aid in the diagnosis of canine distemper encephalomyelitis.

Brain tissue from 33 dogs with non-suppurative encephalitis was examined for evidence of canine distemper virus (CDV) encephalitis. Sections were examined for lesions, inclusion bodies, syncytial cells and CDV antigen using a double bridge unlabelled antibody enzyme technique. Histopathological lesions considered to be typical of granulomatous meningoencephalomyelitis were found in seven dogs. They all lacked inclusion bodies, syncytial cells and CDV antigen. The remaining 26 dogs all had histopathological lesions typical of CDV encephalitis. Inclusion bodies were found in 24 dogs, four of which also had syncytial cells and CDV antigen was detected immunocytochemically in 25. One dog had no inclusion bodies or syncytial cells and was immunohistochemically negative. Syncytial cells have been found to be of limited diagnostic value for the diagnosis of CDV encephalitis. While inclusion bodies proved to be a good diagnostic criterion for the confirmation of CDV infection, the immunohistochemical demonstration of CDV antigen proved to be superior. CDV antigen was more prevalent than inclusion bodies in tissue sections and much more easily detectable.

Polioencephalomalacia (cerebrocortical necrosis) induced by experimental thiamine deficiency in lambs.

Lesions of polioencephalomalacia (PEM, cerebrocortical necrosis) have been demonstrated in pre-ruminant lambs fed on synthetic, thiamine-free milk. Thiamine deficiency in these lambs was confirmed by transketolase assay.

Naturally-occurring neonatal canine herpesvirus infection.

The detailed clinical and epidemiological history and the pathology of neonatal canine herpesvirus (CHV) disease in a naturally infected litter of pups is reported. Herpesvirus was isolated from the brain, lung, liver, spleen, kidney and intestine of one of the affected litter which died on day 10 after whelping. The isolation of virus correlated with the distinctive gross and histological changes in these organs. Herpesvirus was isolated also from the anterior vagina of the bitch 18 days after whelping --a finding which may be of significance in the epidemiology of the natural disease.

Paraquat poisoning in a dog and cat.

Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) has in the last decade gained popularity as an effective weedicide. It is marketed for commercial use as a liquid concentrate Gramoxone ICI (20% paraquat). Accidental or intentional ingestion of Gramoxone has caused 232 human deaths between 1964 and 1973 (Anon 1974). Most human patients suffer transient renal and hepatic insufficiency and pulmonary oedema followed after a latent period by progressive pulmonary fibrosis leading to death from respiratory failure (Harrison 1972). The clinical features of non-fatal paraquet poisoning in a cat and the clinical and pathological findings in fatal poisoning in a dog are reported.

Hereditary nephritis in the bull terrier: evidence for inheritance by an autosomal dominant gene.

A high prevalence of renal failure has been reported in bull terriers in Australia. The pattern of inheritance was analysed in a family of 33 bull terriers in which 10 dogs had renal disease manifested by proteinuria, ultrastructural abnormalities in the glomerular basement membrane, renal failure, or 'end stage' kidneys. The presence of at least one affected parent for each affected offspring, the approximately equal male/female ratio and the apparent absence of 'generation-skipping', strongly supported an autosomal dominant mode of inheritance, assuming a fully penetrant single major gene locus. Further evidence was not compatible with either an autosomal recessive or X-linked inheritance pattern. This contrasts with the X-linked inheritance shown in Alport's-type human hereditary nephritis and hereditary glomerulopathy in the samoyeds. Hereditary nephritis in the bull terrier should be a useful model for non-Alport's-type human hereditary nephritis, which is also reported to have an autosomal dominant inheritance pattern.

Pseudochylous effusion in a cat with cardiomyopathy.

A case of pseudochylous thoracic effusion associated with feline cardiomyopathy is described. At necropsy there was no evidence of structural damage to the thoracic duct or other major lymphatic vessels. The literature covering this syndrome was reviewed and it was concluded that the thoracic effusion may have been associated with congestive heart failure and interference with drainage of the thoracic duct into the anterior vena cava.

The nephrotoxicity of Isotropis forrestii in sheep.

Sheep were drenched with a single toxic dose of dried and milled Isotropis forrestii in water. Intoxication resulted in early onset of glycosuria, enzymuria and proteinuria. Terminal gross lesions included pale kidneys and perirenal oedema. Histologically and ultrastructurally the renal lesions were typical of primary nephrotoxicosis, with extensive proximal tubular epithelial necrosis. The tubular damage was sufficient to cause acute primary renal failure, characterised by oliguria, azotemia and failure of urinary concentrating mechanisms.

Familial nephropathy in cocker spaniels.

A clinical diagnosis of chronic renal failure associated with nephron atrophy and fibrosis was made in 4 blue roan Cocker Spaniels. The lesion was considered to be the result of a primary glomerulopathy. All dogs were closely related. The findings were similar to those previously described for renal cortical hypoplasia. On the basis of the morphological findings and genetic characteristics, the use of the more appropriate term, familial nephropathy is encouraged.

A phalangeal fusion defect and osteochondrosis dissecans with subluxation of the distal interphalangeal joints in a foal.

A fusion defect of the proximal and middle phalanges of both hindlimbs, osteochondrosis dissecans of the distal interphalangeal joints of the forelimbs, and subluxation of all 4 distal interphalangeal joints occurred in a Standardbred filly. Lameness was the first abnormality noted and was observed at one week of age in the left forelimb and progressed until all 4 limbs were affected by 5 weeks of age. On radiographs of both forelimbs, the distal interphalangeal joints were subluxated with irregularity and lucency of subchondral bone. On radiographs of the distal hindlimbs, there was a subluxation of both distal interphalangeal joints and loss of the proximal interphalangeal joint spaces with fusion of the proximal and middle phalanges. The foal was euthanised. On necropsy, there were focal areas of erosion of articular cartilage in the distal interphalangeal joint of both forelimbs. The proximal and middle phalanges of both hindlimbs were fused. Histopathological examination of the distal interphalangeal joint of the right foreleg showed loss of articular cartilage and degenerative changes in the exposed subchondral bone.

Identification of galegine, an isoprenyl guanidine, as the toxic principle of Schoenus asperocarpus (poison sedge).

An isoprenyl guanidine, galegine, was isolated from the Western Australian sedge Schoenus asperocarpus (Cyperaceae). Synthetic galegine was shown to reproduce the clinical and pathological features of poisoning by this plant. Preliminary results suggest that the massive thoracic effusion observed in sedge poisoning is the result of a direct effect on pulmonary vascular permeability.

Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull Terriers.

OBJECTIVE: To describe the renal lesions in Bull Terrier polycystic kidney disease (BTPKD), to confirm that the renal cysts in BTPKD arise from the nephron or collecting tubule, and to identify lesions consistent with concurrent BTPKD and Bull Terrier hereditary nephritis (BTHN). DESIGN: Renal tissue from five Bull Terriers with BTPKD and eight control dogs was examined by light and transmission electron microscopy. Clinical data were collected from all dogs, and family history of BTPKD and BTHN for all Bull Terriers. RESULTS: In BTPKD the renal cysts were lined by epithelial cells of nephron or collecting duct origin that were usually squamous or cuboidal, with few organelles. They had normal junctional complexes, and basal laminae of varying thicknesses. Glomeruli with small, atrophic tufts and dilated Bowman's capsules, tubular loss and dilation, and interstitial inflammation and fibrosis were common. Whereas the lesions seen in BTHN by light microscope were nonspecific, the presence of characteristic ultrastructural glomerular basement membrane (GMB) lesions and a family history of this disease indicated concurrent BTHN was likely in three of five cases of BTPKD. CONCLUSION: This paper provides evidence that renal cysts in BTPKD are of nephron or collecting duct origin. In addition, GBM lesions are described that strongly suggest that BTPKD and BTHN may occur simultaneously.

Stypandra imbricata ("blindgrass") toxicosis in goats and sheep - clinical and pathologic findings in 4 field cases.

Two goats and 2 sheep from field outbreaks of Stypandra imbricata toxicosis had severe lesions in the retina, optic nerves and white matter of the central nervous system. Clinical, ophthalmoscopic, fluorescein angiographic, electroretinographic and histologic atrophy, necrosis and degeneration of axons in the optic nerves and optic tracts and status spongiosus of cerebral white matter.

Induced thiamin deficiency in lambs.

By following a feeding regimen which consistently induced polioencephalomalacia in pre-ruminant lambs it was possible to study certain characteristics just before the terminal stage in polioencephalomalacia. There was always a marked deficit in erythrocyte precursors in bone marrow and this preceded any pathological changes in the brain. Erythrocyte transketolase activity decreased in control lambs, and decreased to an even greater extent in thiamin-deficient lambs. Glucose was the only substrate of those measured which was used by the brain, and its rate of use was not affected by thiamin deficiency. After a single intravenous injection of 35S-thiamin, the decrease of 35S in the plasma was consistent with its dispersal into two pools: the half-time of disappearance of 35S into the slowly equilibrating pool was less in thiamin-deficient lambs than in their controls. Characteristics which were not altered in thiamin deficiency were concentrations of calcium and magnesium in various regions of brain and concentrations of calcium, magnesium, sodium and potassium in plasma.

Clinical and electrocardiographic findings in suspected viral myocarditis of pups.

Surviving puppies from three separate litters in which deaths had occurred from suspected viral myocarditis were examined clinically and electrocardiographically. Of 11 puppies examined, 5 subsequently died or were euthanised within 11 days of initial examination. ECG changes present in these puppies for 1 to 11 days prior to death were small R waves (less than 0.4 mV in lead II), S-T segment elevation, QRS notching and paroxysmal ventricular tachycardia (PVT). No clinical signs referable to the ECG changes were present before the terminal episodes of apparent sudden death or death following a brief period of dyspnoea. Multifocial subacute myocarditis was present on post-mortem examination. A sixth puppy with small R waves remained clinically normal for a further 4 weeks. It then developed severe dyspnoea which persisted for 24 hours before euthanasia. Extensive fibrosis of the left ventricle was present on post-mortem examination.

Progressive tetraparesis and laryngeal paralysis in a young rottweiler with neuronal vacuolation and axonal degeneration: an Australian case.

A 5-month-old female Rottweiler dog was diagnosed to have a neurodegenerative disease that has been recently reported in Rottweilers from North America and Europe. The dog was presented with progressive signs of ataxia, tetraparesis and inspiratory stridor. The clinical investigation included analysis of CSF, radiography, myelography and electrophysiological testing. No evidence of vertebral malformation or inflammatory CNS disease was identified. Bilateral laryngeal paralysis was identified in the lightly anaesthetised dog. Electromyography showed abnormal spontaneous activity from the intrinsic musculature of the larynx. At necropsy there were no gross abnormalities of the nervous system but there was atrophy of the dorsal cricoarytenoid muscles of the larynx. There were widespread histological abnormalities throughout the nervous system including neuronal vacuolation, spongiform changes in the neuropil and axonal degeneration which was most prominent in the spinal cord. These clinical and pathological findings are consistent with the diagnosis of a new neurodegenerative disease reported from North America and Europe. This diagnosis is of particular significance in Australia where transmissible spongiform encephalopathies have not been identified.

Chronic renal disease in bull terriers.

Chronic renal failure was diagnosed in 15 Bull terrier dogs. The dogs ranged in age from one to 8 years. History and clinical findings typically included lethargy, anorexia, polyuria, polydipsia and weight loss. Affected dogs were azotaemic, had elevated serum phosphate and cholesterol, and proteinuria was apparent in all dogs tested (13/13). The concentration of urine was consistently in the nil to minimally concentrated range (specific gravities 1.011-1.017). In those dogs necropsied, both kidneys were approximately two-thirds normal size, tough in consistency, with a pale cortex and a finely nodular capsular surface. Histologically, there was marked nephron loss, diffuse interstitial fibrosis and focal dense radial fibrosis which was especially evident in the renal medulla. Tubular dilation was widespread with focal mineralisation of tubular epithelium and adjacent basement membranes. Glomeruli were often shrunken and segmentally fibrotic. Some Bowman's spaces were extremely dilated. Many less severely affected glomeruli had thickened basement membranes.

Neurological disease and lipofuscinosis in horses and sheep grazing Trachyandra divaricata (branched onion weed) in south Western Australia.

A severe paretic syndrome accompanied by intense neuronal lipofuscinosis is described in sheep and horses exposed to Trachyandra divaricata. This is a newly recognised toxic hazard for grazing livestock in the coastal region of the south west of Western Australia. Animals appear to become affected over a period of weeks when summer conditions induce a scarcity of alternative feed. The disease is discussed in relation to its recent documentation in South Africa where the plant is indigenous.