To compare brain beta-amyloid (Abeta) burden measured with (11)CPittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias.
Thirty-three subjects with dementia (17 ...AD, 10 dementia with Lewy bodies DLB, 6 frontotemporal dementia FTD), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio.
Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis.
Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.
Proliferative and ulcerative typhlitis, colitis, and proctitis were found incidentally in a breeding colony of male athymic nude (Cr:NIH-rnu) rats. Within the crypts of the large intestine, modified ...Steiner's silver stain revealed spiral organisms that were identified by culture, polymerase chain reaction, and sequencing to be Helicobacter bilis. The large bowel disease was reproduced in H. bilis-free male athymic nude rats that were injected intraperitoneally with a culture of H. bilis from the affected colony. The organism was isolated from the feces and cecum of the experimentally infected rats. H. bilis should be considered a potential pathogen in immunocompromised rats. The infection in immunocompromised rats may serve as an animal model for inflammatory large bowel disease.
Objectives To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth ...before stage II. Study design From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed. Results Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only (n = 57). There was significant variation in feeding mode among sites (oral only 0%-81% and G-tube only 0%-56%, P < .01). After adjusting for site, multivariable modeling showed G-tube feeding at discharge was associated with longer hospitalization, and N-tube feeding was associated with greater number of discharge medications ( R2 = 0.65, P < .01). After adjusting for site, mean pre–stage II weight-for-age z -score was significantly higher in the oral-only group (−1.4) vs the N-tube–only (−2.2) and G-tube–only (−2.1) groups ( P = .04 and .02, respectively). Conclusions Feeding mode at hospital discharge after the Norwood procedure varied among sites. Prolonged hospitalization and greater number of medications at the time of discharge were associated with tube feeding. Infants exclusively fed orally had a higher weight-for-age z score pre–stage II than those fed exclusively by tube. Exploring strategies to prevent morbidities and promote oral feeding in this highest risk population is warranted.
Trade credit finance and credit management are gradually gaining the research attention an area of such importance merits. One area, still far from resolved, is why trade credit is extended by ...non-financial firms to customers. This paper seeks to identify the generic forces behind the trade credit offer and to explore the empirical support for 20 propositions on credit motives derived from the literature and the implications of such motives to credit policies. The paper reports findings from a survey of senior finance officers involved in credit management in large UK companies. It assesses the degree to which theoretical explanations for granting trade credit are experienced in practice and whether observed differences attaching to credit motives among firms are associated with variations in credit policies and debtor days. The study found strong empirical support for seven propositions linked to competitiveness, pricing, investment and financing, and weaker support for a number of other theoretically-derived motives for trade credit extension. Factor analysis suggested a more insightful approach to classifying trade credit motives, covering investment in customers, customer's operating and financial benefits, supplier's marketing/operational benefits and market pressure to conform. In addition, two factors-customer relations and pricing flexibility were extracted as motives for varying credit terms. Consistent with our hypothesis average debtor days were found to be significantly higher for those firms emphasising the financing, investment, and pricing flexibility propositions. These findings, and implications for future research, are explored
The complement system is a central component of host defense but can also contribute to the inflammation seen in pathological conditions. The C1s protease of the first complement component, the C1 ...complex, initiates the pathway. In this study we have elucidated the full specificity of the enzyme for the first time using a randomized phage display library. It was found that, aside from the crucial P1 position, the S3 and S2 subsites (in that order) played the greatest role in determining specificity. C1s prefers Leu or Val at P3 and Gly or Ala residues at P2. Apart from the S2′ position, which showed specificity for Leu, prime subsites did not greatly affect specificity. It was evident, however, that together they significantly contributed to the efficiency of cleavage of a peptide. A peptide substrate based on the top sequence obtained in the phage display validated these results and produced the best kinetics of any C1s substrate to date. The results allow an understanding of the active site specificity of the C1s protease for the first time and provide a basis for the development of specific inhibitors aimed at controlling inflammation associated with complement activation in adverse pathological situations.
Hereditary vitamin D resistant rickets (HVDRR) is an autosomal recessive disorder resulting in target organ resistance to the actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In many cases, this ...disorder has been shown to be due to mutations in the gene encoding vitamin D receptors (VDR). In a patient with characteristic features of this disorder, we investigated the functional defect and sequenced the coding region of the gene for mutations.
Skin fibroblasts from patient and control were used to measure binding of 1,25(OH)2D3 and functional responses to the hormone. These cells were also used to prepare RNA from which cDNA was prepared and sequenced. Furthermore, genomic DNA was prepared from the fibroblasts and the intron/exon boundaries sequenced.
A child with classic features of HVDRR with alopecia diagnosed as having rickets due to resistance to 1,25(OH)2D3.
Nuclear association of 1,25(OH)2D3 was determined in patient and control cells and the functional response to 1,25(OH)2D3 was assessed by measurement of 25-hydroxyvitamin D-24-hydroxylase(24-hydroxylase) activity. VDR cDNA and genomic DNA prepared from patient and control cells were sequenced.
Cells from the patient with HVDRR had undetectable amounts of VDR compared to control cells and did not show induction of 24-hydroxylase activity following treatment with 1,25(OH)2D3. Sequencing of the VDR coding region after RT-PCR of RNA revealed an absence of exon 4 in patient RNA which was not due to a deletion in genomic DNA but was caused by exon skipping during RNA processing. In addition, the deletion of exon 4 sequences from RNA leads to a frameshift in translation resulting in a premature stop codon. Amplification of genomic DNA around the intron/exon boundary of exon 4 revealed a point mutation in the 5' donor splice site of intron 4.
In this study, we have identified a novel mutation in the gene for vitamin D receptors in a patient with the characteristic phenotype of hereditary vitamin D resistant rickets. The mutation at the +5 position in intron 4 is most likely to cause skipping of exon 4 in this patient.
: Trade credit terms offer firms contractual solutions to informational asymmetries between buyers and sellers. The credit period permits buyers to reduce uncertainty concerning product quality ...prior to payment, while the seller can reduce uncertainty concerning buyer payment intentions by prescribing payment before/on delivery or through two‐part payment terms and other mechanisms. Variation in trade credit terms also offers firms price discriminating opportunities. This study, drawing on the responses of 700 large firms in the US, UK and Australia, explores trade credit terms through the twin objectives of reducing information asymmetries and discriminatory pricing. Support is found for both theories.
The various surface types involved in the synthesis of DNA upon alcohol-terminated monolayers at Si(111) surfaces were probed using scanning tunneling microscopy (STM). Images of the initial ...hydrogen-terminated layer showed the typical step and terrace features which are retained after alkylation with 4,4‘-dimethoxytrityl-1-undecenol. The method of deprotection for oligonucleotides synthesized at these monolayer films was shown to have a dramatic effect on the surface. After treatment with methylamine, rinsing with water caused considerable etching of the surface; however, this was avoided by the use of a dry ethyl acetate and ether wash. There is little indication of DNA for surfaces covered with single stranded material as judged by STM imaging or tunneling spectroscopy experiments. However, after hybridization with the complementary strand, DNA−Si(111) substrates gave stable images that do not typically show the step and terrace features of the underlying alkyl monolayer. Instead wormlike features are seen that are interpreted as containing aligned DNA molecules lying nearly parallel to the surface.
Complementary strands and redox intercalators can be self‐assembled into nanoscale structures capable of charge transfer at the electrode surface from DNA oligomers synthesized directly at covalently ...modified semiconductor silicon surfaces (see schematic representation).
DNA and alkenyl pyrrole functionalized silicon surfaces allow for the formation of silicon/polypyrrole junctions. These junctions are spatially controlled by photolithography (see Figure) and ...selective photo‐assisted electro‐oxidation of pyrrole. This process shows promise for use in the development of molecular‐based electronic devices, and could enable the deposition of polypyrrole analogously to metal ions in the formation of metallic wires.
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