Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6

Pseudoxanthoma elasticum (PXE) is a systemic heritable disorder that affects the elastic tissue in the skin, eye, and cardiovascular system. Mutations in the ABCC6 gene cause PXE. We performed a mutation screen in ABCC6 using haplotype analysis in conjunction with direct sequencing to achieve a mutation detection rate of 97%. This screen consisted of 170 PXE chromosomes in 81 families, and detected 59 distinct mutations (32 missense, eight nonsense, and six likely splice-site point mutations; one small insertion; and seven small and five large deletions). Forty-three of these mutations are novel variants, which increases the total number of PXE mutations to 121. While most mutations are rare, three nonsense mutations, a splice donor site mutation, and the large deletion comprising exons 23-29 (c.2996_4208del) were identified as relatively frequent PXE mutations at 26%, 5%, 3.5%, 3%, and 11%, respectively. Chromosomal haplotyping with two proximal and two distal polymorphic markers flanking ABCC6 demonstrated that most chromosomes that carry these relatively frequent PXE mutations have related haplotypes specific for these mutations, which suggests that these chromosomes originate from single founder mutations. The types of mutations found support loss-of-function as the molecular mechanism for the PXE phenotype. In 76 of the 81 families, the affected individuals were either homozygous for the same mutation or compound heterozygous for two mutations. In the remaining five families with one uncovered mutation, affected showed allelic compound heterozygosity for the cosegregating PXE haplotype. This demonstrates pseudo-dominance as the relevant inheritance mechanism, since disease transmission to the next generation always requires one mutant allelic variant from each parent. In contrast to other previous clinical and molecular claims, our results show evidence only for recessive PXE. This has profound consequences for the genetic counseling of families with PXE.     

Home care nurses' attitudes toward computers. A confirmatory factor analysis of the Stronge and Brodt instrument

Point-of-care technology for home care use will be the final step in enterprise-wide healthcare electronic communications. Successful implementation of home care point-of-care technology hinges upon nurses' attitudes toward point-of-care technology and its use in clinical practice. This study addresses the factors associated with home care nurses' attitudes using Stronge and Brodt's Nurse Attitudes Toward Computers instrument. In this study, the Nurses Attitudes Toward Computers instrument was administered to a convenience sample of 138 nurses employed by a large midwestern home care agency, with an 88% response rate. Confirmatory factor analysis corroborated the Nurses Attitudes Toward Computers' 3-dimensional factor structure for practicing nurses, which was labeled as nurses' work, security issues, and perceived barriers. Results from the confirmatory factor analysis also suggest that these 3 factors are internally correlated and represent multiple dimensions of a higher order construct labeled as nurses' attitudes toward computers. Additionally, two of these factors, nurses' work and perceived barriers, each appears to explain more variance in nurses' attitudes toward computers than security issues. Instrument reliability was high for the sample (.90), with subscale reliabilities ranging from 86 to 70.     

Effect of dietary manipulations (fasting, hypocaloric feeding, and subsequent refeeding) on rat muscle energetics as assessed by nuclear magnetic resonance spectroscopy.

31P nuclear magnetic resonance (NMR) spectroscopy in vivo and fluorometry were used to measure muscle ATP, total creatine, pH, and Mg2+ in vivo; and to calculate creatine phosphate (CrP), the ratios of CrP/inorganic phosphate (Pi), CrP/ATP, free ADP levels, and the free-energy change in ATP hydrolysis so nutritional effects could be ascertained. These parameters were determined in vivo in resting control, 2-d-fasted, and hypocalorically fed rats and in animals similarly hypocalorically fed and then refed. The ATP, Pi, and intracellular Mg2+ levels were comparable in the four groups. When the fasted and underfed animals were compared with the control and refed animals, there were falls in the ratios of CrP/Pi and CrP/ATP, in the calculated CrP, and the free-energy change of ATP hydrolysis, but a rise in the calculated free ADP. In the hypocaloric group, intracellular pH fell significantly and a large peak was noted in the phosphodiester region. The data are consistent with the hypothesis that ATP levels are maintained at the cost of CrP, suggesting that ATP production is disturbed by aerobic and anaerobic mechanisms.