Disease relevance of NPL

• The strongest evidence of linkage was evident with the pedigrees having <5 family members affected with prostate cancer (multipoint NPL 3.22, P=.00079), a later average age of diagnosis (multipoint NPL 3.40, P=.0006), and no male-to-male transmission (multipoint NPL 3.94, P=.00007) [1].
• Optimized basal-bolus therapy using a fixed mixture of 75% lispro and 25% NPL insulin in type 1 diabetes patients: no favorable effects on glycemic control, physiological responses to hypoglycemia, well-being, or treatment satisfaction [2].
• The region on 14q11 gave evidence for linkage to atopic dermatitis (NPL-score: 2.36, P<0.009) [3].
• We observed suggestive linkage between D1S2890 (1p31, 80.9 cM) and hypertension using the multipoint non-parametric linkage analysis (NPL = 2.19, P = 0.01) [4].
• Immunohistochemistry was used to classify the immunophenotypes of NPL and detect EBV antigen expression [5].

Psychiatry related information on NPL

• For agoraphobia, the most promising potential linkage was on chromosome 3 (NPL score = 2.75; P = 0.005) [6].
• Nonparametric (NPL) analysis provided evidence of linkage for panic disorder/agoraphobia to a locus on chromosome 12q13 (NPL = 4.96, P = 0.006) [7].
• Our studies have shown that subjects with no conscious light perception (NPL) have a higher occurrence and more severe sleep disorders than those with some degree of light perception (LP) [8].
• The present linkage study is a follow-up within the chromosome 3q29 region in schizophrenia and bipolar affective disorder families, based on our recently published genome scan, resulting in evidence for linkage of both disorders to this region (marker D3S1265: NPL [non parametric lod] score Z(all)=3.74, P=0.003) [9].

High impact information on NPL

• The scan, which was performed with a 10-cM framework map, revealed one locus on chromosome 3q13 to which FET mapped with a genome-wide significance when the data were analysed either parametrically, assuming an autosomal dominant model (lod score = 3.71), or non-parametrically (NPL Z score = 4.70, p < 6.4 x 10(-6) [10].
• 4. Multipoint parametric analysis performed by use of GENEHUNTER gave a maximum LOD score of 3.12 for the chromosomal region immediately surrounding the four-marker haplotype D11S4124-D11S2349-D11S1338-D11S1323, and multipoint nonparametric analysis (NPL) confirms this finding (NPL=38.59; P=.000397) [11].
• The following regions had positive multipoint results (HLOD > or =1.0 and/or NPL P< or =.05): chromosomes 1 (90-110 cM), 2 (220-250 cM), 3 (130-150 cM), 4 (140-170 cM), 6 (70-100 cM), 18 (110 cM), and 21 (30-50 cM) [12].
• In the complete set of families, a maximum two-point LOD score of 1.10 was observed at D1S413 (at a recombination fraction [theta] of.1), with a maximum NPL (nonparametric linkage) Z score of 1.64 at D1S202 (P=.05) [13].
• Exclusion from the analysis of kindreds with a phenotype of multiple polyposis also found evidence of linkage in the same region (NPL = 2.47 at close to D9S277, P = 0.009) [14].

Biological context of NPL

• Subsequently, we published the results of a genome scan for linkage to BP disorder using a sample extended to 65 pedigrees in which chromosome 8q24 provided the best finding, an NPL score of 3.13, approaching the accepted score for suggestive linkage [15].
• With additional microsatellite markers, the evidence for linkage for 18q strengthened near 112 cM, where the two-point LOD score for D18S541 was 3.37 and the highest NPL score in that region was 3.65 (P=0.000177) [16].
• Linkage analysis of these candidate gene SNPs with 33 microsatellite markers in families including relative pairs concordantly affected with restricting AN (N=37) substantially increased the evidence for linkage of this region to restricting AN to an NPL score of 3.91 [17].
• NPL is a protamine-based insulin lispro formulation with pharmacokinetics and glucodynamics comparable to those of human NPH insulin [18].
• For UC, the second highest two-point NPL score of 2.00 was observed at proximal 12p13, where also some evidence for linkage disequilibrium emerged (P=0.07 and P=0.007 for the basic and extended IBD cohorts, respectively) [19].

Anatomical context of NPL

• Four markers in the T cell receptor beta chain gene region in 7q35 showed possible linkage (highest NPL score of 1.16) [20].
• The results show no significant difference in the density of GAD65-immunoreactive (-IR) puncta in contact with pyramidal neurons (PN), nonpyramidal neurons (NP), or neuropil (NPL) in sectors CA1-4 and their various sub-laminae [21].
• The NPL Doppler fetal heart beat detector test facility [22].
• 5 mM or 1.0 mM PL mixture based on neonatal (NPL) and adult (APL) composition, and 10 mg/ml mucin with 0.5 mM either APL or NPL mixtures 30 min before a 120-min incubation period at 37 degrees C with 10(8) colony forming units (CFU) of E. coli C25 [23].

Associations of NPL with chemical compounds

• These results indicate that a higher proportion of NPL subjects have abnormal melatonin rhythms compared to those with LP [24].
• FLOSS is specifically designed for use with the Merlin linkage analysis package, but FLOSS can be used with any linkage analysis software package that reports NPL Z-scores for each locus and family [25].
• AIMS: To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily in combination with metformin to that of once-daily insulin glargine plus metformin in patients with Type 2 diabetes inadequately controlled with intermediate insulin, or insulin plus oral agent(s) combination therapy [26].
• The new technique is illustrated using lead data from a Dallas metropolitan area and cadmium data from Palmerton (PA) NPL Superfund site [27].
• A continous flow cell for use with the bendix - NPL automatic polarimeter. Application to neomycin analysis [28].

Other interactions of NPL

• A significant total NPL score of 6.5 for PDS over all families most likely indicated linkage to a genomic region close to PDS [29].
• The new linkage analysis showed stronger evidence for linkage at the Tg gene locus with an MLS of 3.5 between markers D8S514 and D8S284 (NPL = 2.0) [30].
• First, using data from 213 individuals in 59 nuclear families of young-onset hypertension, multipoint analysis revealed a NPL score of 3.02 for the LPL (GZ-14/GZ-15) marker in intron 6 [31].

Analytical, diagnostic and therapeutic context of NPL

• Calibration of the NPL secondary standard radionuclide calibrator for 192Ir brachytherapy sources [32].
• A portable graphite calorimeter is currently being developed at the NPL for measuring absorbed dose in the radiotherapy clinic (McEwen and Duane 2000 Phys. Med. Biol. 45 3675-91) and so factors are now required to be able to convert absorbed dose calibrations from graphite to water in the clinical beam [33].
• Two systems were developed: (1) an HIV-protein ELISA using HIV-protein (also containing HIV-gp120) for the solid phase and NPL as a detector and (2) a lectin-ELISA using the NPL bound to the solid phase and GNL as detector [34].
• A clinical protocol appropriate for interactive and store-and-forward fiber-optic NPL was proposed for further evaluation [35].

References