C. R. Huxtable

Onset and regression of neuroaxonal lesions in sheep with mannosidosis induced experimentally with swainsonine

SummaryA group of young sheep were fed a diet containing theα-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.

Canine Parvoviral Myocarditis: A Morphologic Description of the Natural Disease:

Naturally occurring acute parvoviral myocarditis in puppies 3 to 8 weeks of age was characterised clinically by sudden death or death following a brief period of dyspnoea. Mortality within litters varied from 20% to 100%. The principal lesion was in the myocardium, which in most cases was mottled by pale patches and bands. Moderate to severe pulmonary oedema with marked peribronchial and perivascular oedema was present. In some cases, the wall of the gall bladder was oedematous. Microscopically the ventricular myocardium had myofibre loss, multifocal myofibre necrosis, a mononuclear cell infiltrate of variable intensity and reactive stromal elements. In every case there were Feulgen-positive, amphophilic, intranuclear inclusion bodies in myocardial nuclei. Ultrastructurally the inclusions were composed of dense granular material and particles resembling parvovirions. Pulmonary alveolar septae were thickened by fibroblasts. Peribronchial and perivascular lymphatics were distended with oedema fluid and occasionally erythrocytes. The pulmonary lesions were considered secondary to the myocardial dysfunction. Some of the puppies that survived the acute disease developed ventricular myocardial fibrosis and died in congestive heart failure.

Canine Laryngeal Oncocytomas

Solitary, protruding tumors were found in the wall of the larynx in three adult dogs with clinical upper respiratory obstruction. They were composed of cells with abundant granular acidophilic cytoplasm, the granularity caused by an unusually large number of mitochondria. The lesions were considered to be neoplasms arising from oncocytes as described in man. Oncocytomas have not been reported previously in domestic animals.

The pathology of disseminated Aspergillus terreus infection in dogs.

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.

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.

Mannoside storage and axonal dystrophy in sensory neurones of swainsonine-treated rats: Morphogenesis of lesions

SummaryYoung 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.

Dianellidin, stypandrol and dianellinone: An oxidation-related series from dianella revoluta

Dianellidin, stypandrol and dianellinone were isolated from Dianella revoluta and were considered with respect to their biosynthetic relationship and to the toxicity of Stypandra imbricata.

Clinicopathologic principles for veterinary medicine

Preface Acknowledgements 1. The relationship between pathology and medicine Wayne F. Robinson and Clive R. R. Huxtable 2. The immune system W. John Penhale 3. The hematopoietic system Jennifer N. Mills and V. E. O. Valli 4. Acid-base balance Leonard K. Cullen 5. The respiratory system David A. Pass and John R. Bolton 6. The cardiovascular system Wayne F. Robinson 7. The alimentary tract John R. Bolton and David A. Pass 8. The liver and exocrine pancreas Clive R. R. Huxtable 9. The urinary system Clive R. R. Huxtable 10. The endocrine glands Wayne F. Robinson and Susan E. Shaw 11. The skin Clive R. R. Huxtable and Susan E. Shaw 12. The skeletal system Wayne F. Robinson, Robert S. Wyburn and John Grandage 13. The nervous system Clive E. Eger, John McC. Howell and Clive R. R. Huxtable 14. Muscle Wayne F. Robinson 15. Metabolic disease David W. Pethick 16. The reproductive system Peter E. Williamson Index.

Stypandrone: A toxic naphthalene-14-quinone from Stypandra imbricata and Dianella revoluta

A compound, previously not isolated from dried, milled samples of Stypandra imbricata and Dianella revoluta, has now been obtained from fresh samples of these plants. The structure was shown, by spectroscopic techniques, to be identical to that of stypandrone. This quinone was found to be toxic to laboratory mice. However, it produces a different toxic effect to that observed when livestock ingest fresh Stypandra imbricata or when stypandrol is administered to laboratory mice.

Nephrotic Syndrome and Collagenizing Glomerulopathy in PVG/c Rats Treated with the α-mannosidase Inhibitor “Swainsonine”

Weanling PVG/c rats treated with the α-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.