Partial and severe factor XI deficiency in South Australia and the usefulness of factor XI mutation analysis for diagnosis.

AIMS: To correlate the presence or absence of a factor XI gene mutation with factor XI activity in patients with severe or partial reduction in factor XI. METHODS: Patients previously found to have reduced factor XI levels were recalled for repeat testing and factor XI genetic analysis. Also, during the 18 month study period, any routine patient found to have an isolated reduced or low normal factor XI level had factor XI genetic analysis. RESULTS: Twenty-two cases were studied and 11 with factor XI from <2 to 57 U/dL (reference 55-130 U/dL), were found to have a factor XI gene mutation. Gene sequencing identified 15 different mutations, with four patients found to be compound heterozygotes. One patient with no bleeding history had a novel polymorphism which family studies showed was not associated with his low factor XI. No factor XI gene abnormality was detected in 10 patients and they have either acquired causes of deficiency or factor XI levels in the lower portion of the normal range. CONCLUSION: Genetic analysis of the factor XI gene is important to confirm or exclude inherited causes of factor XI deficiency, especially when the reduction is mild.

Characterization and use of the NSC-34 cell line for study of neurotrophin receptor trafficking.

This study addressed the suitability of the NSC-34 cell line as a motor neuron-like model for investigating neurotrophin receptor trafficking and associated subcellular processes. Initially, culture conditions were optimized for the use of NSC-34 cells in confocal microscopy. Cell surface markers, as well as markers associated with the regulated endosomal pathway thought to be associated with neurotrophin receptor transport, were identified. The study revealed the presence of a number of molecules previously not described in the literature, including the tropomyosin-like receptor kinase C (TrkC), sortilin, the vesicular acetylcholine transporter (VAChT), and the lipid raft-associated ganglioside GT1b. The presence of both sortilin and Gt1b was of special interest, insofar as these markers have been implicated in direct relationships with the p75NTR receptor. Evidence is provided for neurotrophin-dependent internalization of p75NTR and TrkB. Both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) increased the rate of internalization of p75NTR, with internalization dynamics comparable to those described for other cell lines. Thus, these studies not only describe components of the regulatory process governing the trafficking of this important receptor but also clearly demonstrate the value of NSC-34 cells as a suitable motor neuron model for the study of internalization and trafficking of cell surface molecules.