Sequence diversity in genes of lipid metabolism.

Elevated plasma lipoprotein levels play a crucial role in the development of coronary artery disease. Genetic factors strongly influence the levels of plasma lipoproteins, but the genes and sequence variations contributing to the most common forms of dyslipidemias are not known. We used GeneChip probe arrays to resequence the coding regions of 10 key genes of lipid metabolism. The sequences of these genes were analyzed in 80 dyslipidemic individuals. Fourteen nonsynonymous and twenty-two synonymous single nucleotide changes were identified that could be confirmed by conventional sequencing. Seven of the fourteen nonsynonymous sequence variants were polymorphisms with allele frequency >1% in the general population. The remaining seven were not found in normolipidemic controls (25 Caucasians and 25 African-Americans). The relationship between nonsynonymous sequence variations and various dyslipidemias was explored in association and family studies. No evidence was found for coding sequence variations in any of the 10 genes contributing to dyslipidemia. Only a single sequence variation, a missense mutation in the low density lipoprotein receptor gene, co-segregated with hyperlipidemia in the proband's family. This study illustrates some of the difficulties associated with identifying sequence variations contributing to complex traits.

One for you and two for me: revenue sharing arrangements in charitable healthcare organizations.

Charitable healthcare organizations have often borrowed from the methods of their for-profit counterparts in compensating physicians and other business partners. This is done in order to provide needed services to their communities, and to protect their charitable assets by sharing risk and preserving limited capital. One of the most controversial compensation methods in use by such organizations is the revenue sharing arrangement. In use for over thirty years, these arrangements have received close scrutiny and inconsistent treatment by the Internal Revenue Service (IRS) and have been the subject of critics' ire as an impermissible transgression of the fundamental line between charities and commercial enterprises. The author, however, concludes that revenue sharing arrangements serve an important purpose in enabling charitable healthcare organizations to fulfill their missions, that the IRS and the Treasury have now made clear that there is not a higher standard governing their use, and that these arrangements are consistent with charitable operation when an appropriate process and safeguards are in place to prevent payment of unreasonable compensation.

Sequence, expression, and location of zebrafish frizzled 10.

Members of the frizzled gene family encode seven-pass transmembrane proteins that function in the interpretation and reception of Wnt-mediated cell-cell communication events. To investigate frizzled function in early zebrafish development, we isolated the maternally contributed frizzled 10 (fz10) gene and localized it to linkage group 8 using radiation hybrid mapping. The cloned zebrafish fz10 is closely related to the fz10 group from other organisms. Zygotic expression of fz10 is observed in the posterior tail mesenchyme, dorsal neural tube, and different parts of the brain.

Evidence for a frizzled-mediated wnt pathway required for zebrafish dorsal mesoderm formation.

We have used zebrafish as a model system for the study of vertebrate dorsoventral patterning. We isolated a maternally expressed and dorsal organizer localized member of the frizzled family of wnt receptors. Wild-type and dominant, loss-of-function molecules in misexpression studies demonstrate frizzled function is necessary and sufficient for dorsal mesoderm specification. frizzled activity is antagonized by the action of GSK-3, and we show GSK-3 is also required for zebrafish dorsal mesoderm formation. frizzled cooperatively interacts with the maternally encoded zebrafish wnt8 protein in dorsal mesodermal fate determination. This frizzled -mediated wnt pathway for dorsal mesoderm specification provides the first evidence for the requirement of a wnt-like signal in vertebrate axis determination.

Recent developments for tax-exempt healthcare organizations.

Significant developments in the law of tax-exempt healthcare organizations occurred during the early 1990s. The span of developments includes a seminal Seventh Circuit case, Living Faith v. Commissioner, as well as an Internal Revenue Service determination letter recognizing the charitable tax status of integrated delivery systems, showing the recent activitism of the IRS in the healthcare arena. In addition, the federal and state courts have struggled to define and apply concepts of community benefit and charity to modern healthcare organizations.

Strategies can enhance rural hospital viability.

Although some rural hospitals struggle to remain financially viable, the Internal Revenue Service (IRS) often shows greater flexibility in interpreting regulations for tax-exempt hospitals in rural areas. To take advantage of this flexibility, rural facilities should understand issues affecting Federal tax-exempt status, such as private benefit, private inurement, and unrelated business income. A not-for-profit, rural healthcare facility well versed in tax-exempt regulations and their interpretations by the IRS can structure recruitment and retention programs, joint ventures, unrelated businesses, and even cooperative coalitions to enhance its financial well-being without endangering its tax exemption.