Biomedical subjects
Publications and source records attributed to C R Huxtable.
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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.
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.
Clinical and pathological findings are reported from a series of 12 cases of disseminated aspergillosis (A. terreus) in 11 German Shepherd dogs and one Dalmatian referred to Murdoch University Veterinary Hospital (MUVH) over the period 1980 to 1984. A preliminary study of humoral and cell mediated immune components and complement levels revealed no consistent abnormality in 9 dogs tested apart from raised IgG levels. Serum IgA levels were depressed in 30% of cases. Serial data from one extensively monitored case is presented. The unusual epidemiological and pathogenetic features of the disease are discussed.
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.
Young rats were treated with swainsonine for up to 200 days at a dose rate that restricted neuronal mannoside storage to neurones not protected by the blood/brain barrier. In lumbar dorsal root ganglion neurones, mannoside storage in the cell body developed in parallel to dystrophic changes at the extremities of peripherally and centrally directed axons. The dystrophic process involved the accumulation of autophagic structures. In the CNS, axonal dystrophy was confined to areas receiving long processes from affected neurones. The results suggest that axonal dystrophy is a direct consequence of the lysosomal storage process in parent cell bodies. The possible relationship of axonal dystrophy to neuronal lysosomal function is discussed.
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.
Disseminated Aspergillus terreus infection was diagnosed in ten previously healthy adult dogs--nine German shepherds and one dalmatian. The disease was characterized by the presence of multiple granulomas and infarcts in a wide range of organs. The kidney, spleen, and skeletal system were most commonly and severely affected. Fungal hyphae were demonstrated in large numbers within granulomas and thrombi, and A. terreus was readily isolated by culture. This disseminated mycosis appears unique; in this series of cases there was no apparent predisposing factor, portal of entry, or primary focus for dissemination of the infection.
Weanling PVG/c rats treated with the alpha-mannosidase inhibitor swainsonine developed increasing proteinuria which terminated as a severe nephrotic syndrome after 35 to 45 days. This was associated with a glomerulopathy characterized by the production of collagen fibrils adjacent to endothelial and mesangial cells, foot process expansion, subepithelial projections of the basement membrane, and splitting of the lamina densa. The swainsonine-induced glomerulopathy appeared to be an exacerbation of a spontaneous abnormality in this strain of rat.
A group of young sheep were fed a diet containing the alpha-mannosidase inhibitor swainsonine, which resulted in the induction of a neuronal lysosomal mannoside storage disease. Sheep were killed at various intervals during and following the treatment period and the nature and distribution of neuronal and axonal lesions in the brain were assessed by routine light and electron microscopy and by the rapid Golgi impregnation technique. Neuronal mannoside storage, axonal dystrophy and meganeurite formation were induced by 80 days of treatment and the lesions had regressed by 40 days after the end of treatment. The results are discussed in relation to their relevance to the current widespread interest in the pathobiology of neuronal lysosomal storage.
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.
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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.
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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.
An indolizidine alkaloid (swainsonine) was isolated from the plant Swainsona canescens. Swainsonine is a specific and potent inhibitor of alpha-mannosidase (EC 3.2.1.24) and when administered to animals produces a phenocopy of the genetically based lysosomal storage disease, mannosidosis. Evidence is presented to suggest that swainsonine is a reversible active site-directed inhibitor of lysosomal alpha-mannosidase.
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