The NIK protein kinase and C17orf1 genes: chromosomal mapping, gene structures and mutational screening in frontotemporal dementia and parkinsonism linked to chromosome 17

Full exon-intron structures are presented for the NIK serine/threonine protein kinase gene and a novel gene termed C17orf1. By in situ hybridisation and radiation hybrid mapping, a cosmid (cDD-Z) that contains regions of both of these genes has been localised between markers D17S800 and D17S791 at chromosome 17q21. The two genes are thus positional candidates for the mutant locus underlying frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), a disease for which NIK is also a good biological candidate. Using exon-intron maps, a genomic DNA sequencing based mutation screen has been performed for the NIK and C17orf1 genes in a chromosome 17-linked FTDP-17 pedigree. Two silent single-base variations were detected in C17orf1. No alterations were restricted to DNA samples from patients, thus excluding the C17orf1 and NIK genes as likely sites of mutation FTDP-17. Received: 23 December 1997 / Accepted: 23 June 1998     

A Multi-laboratory in Vitro Study to Compare Data from Abbreviated and Pharmacopeial Impactor Measurements for Orally Inhaled Products: a Report of the European Aerosol Group (EPAG)

Fine particle dose (FPD) is a critical quality attribute for orally inhaled products (OIPs). The abbreviated impactor measurement (AIM) concept simplifies its measurement, provided there is a validated understanding of the relationship with the full resolution pharmacopoeial impactor (PIM) data for a given product. This multi-center study compared fine particle dose determined using AIM and PIM for five dry powder inhaler (DPIs) and two pressurized metered-dose inhaler (pMDI) products, one of which included a valved holding chamber (VHC). Reference measurements of FPD_PIM were made by each organization using either the full-resolution Andersen 8-stage non-viable impactor (ACI) or Next Generation Impactor (NGI). FPD_AIM was determined for the same OIP(s) with their choice of abbreviated impactor (fast screening impactor (FSI), fast screening Andersen (FSA), or reduced NGI (rNGI)). Each organization used its validated assay method(s) for the active pharmaceutical ingredient(s) (APIs) involved. Ten replicate measurements were made by each procedure. The upper size limit for FPD_AIM varied from 4.4 to 5.0 μm aerodynamic diameter, depending upon flow rate and AIM apparatus; the corresponding size limit for FPD_PIM was fixed at 5 μm in accordance with the European Pharmacopoeia. The 90% confidence interval for the ratio [FPD_AIM/FPD_PIM], expressed as a percentage, was contained in the predetermined 85–118% acceptance interval for nine of the ten comparisons of FPD. The average value of this ratio was 105% across all OIPs and apparatuses. The findings from this investigation support the equivalence of AIM and PIM for determination of FPD across a wide range of OIP platforms and measurement techniques.