Osamu Yamato

Hemolytic anemia in wild seaducks caused by marine oil pollution.

Clinico-pathological examinations were conducted on wild white-winged scoters (Melanitta fusca) contaminated with fuel oil (Bunker C oil) from a capsized cargo ship in February 1993 in Japan. The erythrocyte count, hemoglobin concentration and hematocrit value in the oiled seaducks all were decreased and numerous immature erythrocytes were observed in blood smears. In addition, hemosiderosis was observed in the liver, kidney, and lung of some birds. We propose that the seaducks suffered from hemolytic anemia induced by ingestion of oil, which occurs when the birds preen their oiled plumage.

Sandhoff disease in a golden retriever dog

A golden retriever dog is described with total hexosaminid ase deficiency and raised GM2-ganglioside in CSF. The animal represents a model for human Sandhoff disease.

Reduced glutathione accelerates the oxidative damage produced by sodium n-propylthiosulfate, one of the causative agents of onion-induced hemolytic anemia in dogs.

The oxidative effects of sodium n-propylthiosulfate, one of the causative agents of onion-induced hemolytic anemia in dogs, were investigated in vitro using three types of canine erythrocytes, which are differentiated by the concentration of reduced glutathione and the composition of intracellular cations. After incubation with sodium n-propylthiosulfate, the methemoglobin concentration and Heinz body count in all three types of erythrocytes increased and a decrease in the erythrocyte reduced glutathione concentration was then observed. The erythrocytes containing high concentrations of potassium and reduced glutathione (approximately five times the normal values) were more susceptible to oxidative damage by sodium n-propylthiosulfate than were the normal canine erythrocytes. The susceptibility of the erythrocytes containing high potassium and normal reduced glutathione concentrations was intermediate between those of erythrocytes containing high concentrations of potassium and reduced glutathione and normal canine erythrocytes. In addition, the depletion of erythrocyte reduced glutathione by 1-chloro-2, 4-dinitrobenzene resulted in a marked decrease in the oxidative injury induced by sodium n-propylthiosulfate in erythrocytes containing high concentrations of potassium and reduced glutathione. The generation of superoxide in erythrocytes containing high concentrations of potassium and reduced glutathione was 4.1 times higher than that in normal canine erythrocytes when the cells were incubated with sodium n-propylthiosulfate. These observations indicate that erythrocyte reduced glutathione, which is known as an antioxidant, accelerates the oxidative damage produced by sodium n-propylthiosulfate.

GM1 gangliosidosis in shiba dogs

A six-month-old shiba dog with a one-month history of progressive motor dysfunction showed clinical signs of a cerebellar disorder, including ataxia, dysmetria and intention tremor of the head. Histopathological and ultrastructural studies revealed distended neurons packed with membranous cytoplasmic bodies throughout the central nervous system. The activities of lysosomal acid β-galactosidase in its leucocytes and liver were less than 2 per cent of the control levels, and the compound accumulated in the brain was identified as GM1 ganglioside. A sibling which died immediately after birth was shown to have a β-galactosidase deficiency in the brain and visceral organs. A family study revealed that the sire and dam of the probands were heterozygotes with approximately half of the normal level of β-galactosidase activity, suggesting an autosomal recessive pattern of inheritance.

Comparative study of chronic kidney disease in dogs and cats: Induction of myofibroblasts

We investigated the kidneys of dogs and cats to clarify whether renal myofibroblasts induction is associated with the severity of chronic kidney disease (CKD). Immunohistochemical expression of myofibroblast markers, alpha-smooth muscle actin (SMA) and vimentin, were evaluated quantitatively. The degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration, and interstitial fibrosis were also evaluated quantitatively. The plasma creatinine (pCre) concentrations correlated with glomerulosclerosis, cell infiltration, and fibrosis in dogs, and only with fibrosis in cats. The alpha-SMA expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, and with pCre and fibrosis in cats. Tubular vimentin expression correlated with fibrosis in cats, but not in dogs. Interstitial vimentin expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, but only with pCre in cats. In conclusion, it was suggested that the severity of CKD in dogs and cats was mediated by different pathways associated with myofibroblasts expression.

Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis : possible use for assessment of a therapeutic regimen

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.

Heinz Body Hemolytic Anemia With Eccentrocytosis From Ingestion of Chinese Chive (Allium tuberosum) and Garlic (Allium sativum) in a Dog

A 4-year-old, intact male miniature schnauzer was presented with anorexia. The dog had ingested some Chinese steamed dumplings 2 days before, which contained Chinese chive (Allium tuberosum) and garlic (Allium sativum). Hematological examinations revealed severe Heinz body hemolytic anemia with eccentrocytosis and an increased concentration of methemoglobin, which was thought to result from oxidative damage to erythrocytes by constituents in these Allium plants. In this case, eccentrocytosis was a hallmark finding and could be detected easily, suggesting that this hematological abnormality is useful in diagnosing Allium plant-induced hemolysis.

GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats

A five-month-old, female Japanese domestic shorthair cat with proportionate dwarfism developed neurological disorders, including ataxia, decreased postural responses and generalised body and head tremors, at between two and five months of age. Leucocytosis due to lymphocytosis with abnormal cytoplasmic vacuolations was observed. The concentration of GM2-ganglioside in its cerebrospinal fluid was markedly higher than in normal cats, and the activities of β-hexosaminidases A and B in its leucocytes were markedly reduced. On the basis of these biochemical data, the cat was diagnosed antemortem with GM2-gangliosidosis variant 0 (Sandhoff-like disease). The neurological signs became more severe and the cat died at 10 months of age. Histopathologically, neurons throughout the central nervous system were distended, and an ultrastructural study revealed membranous cytoplasmic bodies in these distended neurons. The compound which accumulated in the brain was identified as GM2-ganglioside, confirming GM2-gangliosidosis. A family study revealed that there were probable heterozygous carriers in which the activities of leucocyte β-hexosaminidases A and B were less than half the normal value. The Sandhoff-like disease observed in this family of Japanese domestic cats is the first occurrence reported in Japan.

A novel mutation in the gene for canine acid β-galactosidase that causes GM1-gangliosidosis in Shiba dogs

A homozygous recessive mutation, causing GM1-gangliosidosis in Shiba dogs, was identified as a deletion of C nucleotide 1668 in the gene for canine acid β-galactosidase, which was a novel mutation in canine GM1-gangliosidosis.

Induction of onion-induced haemolytic anaemia in dogs with sodium n-propylthiosulphate

The haemolytic effect of sodium n-propylthiosulphate, which had been isolated from boiled onions, was studied to determine whether it could be one of the agents responsible for induced haemolytic anaemia in dogs. The oral administration of 500 μmol/kg bodyweight of the compound to dogs resulted in a haemolytic anaemia associated with an increase of Heinz body formation in erythrocytes, which was more severe in dogs with the hereditary condition which results in erythrocytes with high concentrations of reduced glutathione and potassium than in normal dogs. In the affected dogs there was a 10-fold increase in the concentration of oxidised glutathione in their erythrocytes 12 hours after the administration of the compound, whereas in normal dogs there was almost no change.