We studied bovine subjects that exhibited a moderate uncompensated anemia with hereditary spherocytosis inherited in an autosomal incompletely dominant mode and retarded growth. Based on the results of SDS-PAGE, immunoblotting, and electron microscopic analysis by the freeze fracture method, we show here that the proband red cells lacked the band 3 protein completely. Sequence analysis of the proband band 3 cDNA and genomic DNA showed a C → T substitution resulting in a nonsense mutation (CGA → TGA; Arg → Stop) at the position corresponding to codon 646 in human red cell band 3 cDNA. The proband red cells were deficient in spectrin, ankyrin, actin, and protein 4.2, resulting in a distorted and disrupted membrane skeletal network with decreased density. Therefore, the proband red cell membranes were extremely unstable and showed the loss of surface area in several distinct ways such as invagination, vesiculation, and extrusion of microvesicles, leading to the formation of spherocytes. Total deficiency of band 3 also resulted in defective Cl Ϫ /HCO 3 Ϫ exchange, causing mild acidosis with decreases in the HCO 3

Background: Imatinib mesylate is a small molecule targeted at dysregulated protein-tyrosine kinase. Mutation of c-kit exon 11, which induces constitutive phosphorylation of KIT, is one of the mechanisms for the development or progression of mast cell tumor (MCT) in dogs. The purpose of this study was to examine the therapeutic potential of imatinib mesylate in canine MCT.Hypothesis: Imatinib mesylate has activity against MCT in dogs, and response to treatment can be correlated to presence of mutation within exon 11 of c-kit.Animals: Twenty-one dogs with MCT with gross tumor burden and median tumor size of 7.2 cm (range, 1.0-25.3 cm) before treatment.Methods: Tumors were analyzed for mutation of c-kit exon 11. Imatinib mesylate was administered PO to the dogs at a dose of 10 mg/kg daily for 1-9 weeks.Results: Ten of 21 dogs (48%) had some beneficial response to imatinib mesylate treatment within 14 days of treatment initiation. All 5 dogs with a demonstrable c-kit mutation in exon 11 responded to the drug (1 complete remission, 4 partial remission).Conclusions and Clinical Importance: Imatinib mesylate has clinical activity against MCT in dogs. Response could not be predicted based on presence of absence of a mutation in exon 11 of c-kit.

The factors affecting outcome were analyzed in 1,064 patients, 621 males and 443 females aged 10 to 104 years (mean 46 ± 23 years), with mild head injury (Glasgow Coma Scale [GCS] score AE14) but no neurological signs presenting within 6 hours after injury. Intracranial lesion was found in 4.7% (50/1,064), and 0.66% (7/1,064) required surgical treatment. The Japan Coma Scale (JCS) and GCS assessments were well correlated (r ＝ 0.797). Multivariate analysis revealed significant correlations between computed tomography (CT) abnormality and age AE60 years, male sex, JCS score AE1, alcohol consumption, headache, nausea/vomiting, and transient loss of consciousness (LOC)/amnesia. Univariate analysis revealed that pedestrian in a motor vehicle accident, falling from height, and mechanisms of injuries except blows were correlated to intracranial injury. No significant correlations were found between craniofacial soft tissue injury and intracranial injury. Patients with occipital impact, nonfrontal impact, or skull fracture were more likely have intracranial lesions. Bleeding tendency was not correlated with CT abnormality. The following indications were proposed for CT: JCS score À0, presence of accessory symptoms (headache, nausea/vomiting, LOC/amnesia), and age AE60 years. These criteria would reduce the frequency of CT by 29% (309/1,064). Applying these indications to subsequent patients with GCS scores 14-15, 114 of 168 patients required CT, and intracranial lesions were found in 13. Two refused CT. Fifty-four of the 168 patients did not need CT according to the indications, but 38 of the 54 patients actually underwent CT because of social reasons (n ＝ 21) or patient request (n ＝ 17). These indications for CT including JCS may be useful in the management of patients with mild head injury.

ABSTRACT. To examine the prevalence of autoantibody in canine cerebrospinal fluids (CSFs), CSFs were collected from 14 healthy controls and 88 clinical cases with various diseases in the central nervous system (CNS), and were analyzed by an indirect fluoresc ence antibody test on frozen sections of the cerebrum from normal Beagle dogs. An anti-astrocyte autoantibody was detected in 31 clinica l cases with titers ranging from 1:1 to ≥1:100. All tested cases with necrotizing meningoencephalitis (NME: n=22) and granulomatous meningoencephalitis (GME: n=3) possessed the anti-astrocyte autoantibody, while the autoantibody was negative in most cases with other inflammatory CNS diseases. The autoantibody was also detected in 4 of 12 cases with brain tumors. Hence, examination of the au toantibody in the canine CFS would be significant for diagnosing NME and/or GME, as well as for understanding peritumoral events in cases with brain tumors.

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