sive disappearance of the V379I BCR-ABL allele and its replacement by a novel BCR-ABL allele (Figure 1, lanes 4-6, band c). Direct sequencing further characterized a double mutation V379I and T315I (Figure S1, available at the Blood website; see the Supplemental Figure link at the top of the online letter). It is noteworthy that the 2 mutations were present on the same allele, since only 1 band...

The hereditary disorders chorea acanthocytosis and Cohen syndrome are caused by mutations in different members of a family of genes that are orthologs of yeast VPS13. In vegetatively growing yeast, VPS13 is involved in the delivery of proteins to the vacuole. During sporulation, VPS13 is important for formation of the prospore membrane that encapsulates the daughter nuclei to give rise to spore...

The nonreceptor tyrosine kinase encoded by the c-Abl gene has the unique feature of an F-actin binding domain (FABD). Purified c-Abl tyrosine kinase is inhibited by F-actin, and this inhibition can be relieved through mutation of its FABD. The c-Abl kinase is activated by physiological signals that also regulate the actin cytoskeleton. We show here that c-Abl stimulated the formation of actin m...

The Abl non-receptor tyrosine kinase has been implicated in a wide variety of cellular processes, yet its function and regulation remain poorly understood. Abl has resisted complete understanding not due to lack of interest, but due to the complexity of its overall structure and the corresponding complexity and diversity of its biological activities in the cell. Although Abl consists of many fa...

BACKGROUND Episodic non-ketotic hyperglycaemia in patients with diabetes may be responsible for a syndrome characterised by hemichorea-hemiballism associated with unique radiological features. OBJECTIVE To investigate whether factors other than hyperglycaemia may be responsible for the neurological involvement. METHODS Three patients who developed a persistent chorea-ballism syndrome trigge...

High density lipoprotein subfraction-1 (HDL(1)) is thought to interact with the high-affinity apoprotein B, E receptors of peripheral cells and may act as a modulator of LDL binding and uptake. In the present study the concentration and composition of HDL(1) in normal and hypercholesterolemic sera were studied using zonal ultracentrifugation. To permit separation of the HDL(1) from VLDL, LDL, a...

The Abl family nonreceptor tyrosine kinases, consisting of closely related Abl and Arg (Abl-related gene), play essential roles in mouse neurulation, but their functions in the subsequent development of CNS are poorly understood. Here, we show that conditional deletion of Abl in precursors of neurons and glia on an Arg knock-out background leads to striking cerebellar malformations, including d...

Intracortical inhibition of the motor cortex was investigated using a paired pulse magnetic stimulation method in 14 patients with chorea caused by various aetiologies (six patients with Huntington's disease, one with chorea acanthocytosis, a patient with systemic lupus erythematosus with a vascular lesion in the caudate, three with senile chorea and three with chorea of unknown aetiology). The...

TNF-Related Apoptosis Inducing Ligand (TRAIL) binds to and activates death receptors to stimulate caspase-8 and apoptosis with higher efficiency in cancer than normal cells but the development of apoptosis resistance has limited its clinical efficacy. We found that stable, but not transient knockdown of the ABL tyrosine kinase enhanced the apoptotic response to TRAIL. Re-expression of Abl, but ...

SUMMARY Neuroacanthocytosis is a rare hereditary disorder characterized by involuntary choreiform movements and erythrocytic acanthocytosis in the peripheral blood. Clinical manifestations of this disorder resemble those of Huntington disease (HD). Neuroimaging features of neuroacanthocytosis are atrophy and signal intensity change of the striata on MR imaging, as in HD. We report herein the ca...