Overcoming the problems associated with poor spectra quality of the protein kinase Byr2 using residual dipolar couplings.

For the Ras-binding domain of the protein kinase Byr2, only a limited number of NOE contacts could be initially assigned unambiguously, as the quality of the NOESY spectra was too poor. However, the use of residual (1)H-(15)N dipolar couplings in the beginning of the structure determination process allows to overcome this problem. We used a three-step recipe for this procedure. A previously unknown structure could be calculated reasonably well with only a limited number of unambiguously assigned NOE contacts.

Molecular alignment of proteins in bicellar solutions: quantitative evaluation of effects induced in 2D COSY spectra.

Partial molecular alignment leads to an incomplete averaging of anisotropic magnetic interactions such as magnetic dipole interaction or chemical shift anisotropy. In the present contribution we quantitatively describe and evaluate the effects induced by the addition of magnetically oriented lipid bicelles in homonuclear two-dimensional (2D) NMR correlation (COSY) spectra of proteins. It is shown that 2D COSY experiments allow the measurement of H(N)-H(alpha) residual dipole couplings of positive sign which can be used for structure refinement. In contrast to the double- and triple-resonance experiments previously proposed, these measurements can be carried out even on nonisotope-enriched samples.

Current efforts toward implementation of an urban health strategy: the Henry Ford Health System.

The Henry Ford Health System is one of the nation's major comprehensive nonprofit health systems. Though it serves seven counties in southeastern Michigan, it is based in the heart of the city of Detroit. Detroit, like many of the nation's largest cities, has high rates of poverty, single-parent households, unemployment, and violence. The health status of the population is well below national norms and Healthy People 2000 goals. Through the combined efforts of public and private organizations and the people of southeastern Michigan, Detroit is experiencing a renaissance. Henry Ford Health System is contributing to this renaissance and is working to define its role in improving the health status and quality of life of Detroit's residents. The system's current strategy centers on moving beyond civic projects and philanthropic efforts to the incorporation of care for the uninsured and underinsured in its core operations and plans for growth. To make this change, we have developed a systemwide process that focuses on designing and implementing new delivery models, on partnership development with a variety of organizations, and on managing the care of populations. Our efforts are a work in progress, but they are having an impact on our patients, our organization, and our community.

Prolonged infusions of Ile5-angiotensin-II in sodium replete and deplete man: effects on aldosterone, ACTH, cortisol, blood pressure, and electrolyte balance.

Angiotensin II (Ile5) was infused for 72 h into 4 sodium replete (3 ng/kg/min) and 8 sodium deplete (3 or 6 ng/kg/min) healthy young men after appropriate control periods, and the effects on aldosterone secretion, plasma cortisol, ACTH, renin activity, plasma and urinary electrolytes, and blood pressure were assessed. Sustained contrived elevation of plasma angiotensin II levels in sodium replete subjects to the range of moderate sodium depletion led to a sustained increase in plasma and urinary aldosterone levels, which further and significantly increased between the 1st and 2nd days of angiotensin II infusion, when gross sodium retention during infusion was prevented. This additional increase may be explained as the expression of a "trophic" effect of angiotension II on the zona glomerulosa. In the sodium deplete state, the absolute increment of aldosterone secretion for a given elevation of angiotensin II levels diring infusion was larger than in sodium replete subjects. This confirms the conclusions from previous short-term angiotensin II infusion experiments that sodium deficiency sensitizes the zona glomerulosa against angiotensin II. The "trophic" effect of angiotensin II on the adrenal gland seems to be one mechanism by which the sensitization is brought about, but insufficient for its full explanation. Since plasma ACTH and cortisol, plasma sodium and potassium concentrations, and potassium blance did not change significantly across sodium depletion or angiotensin II infusion, the mechanism of sensitization awaits its full elucidation. The effect of angiotensin II on blood pressure was blunted by soidum depletion. The opposite shifts in sensitivity against angiotensin II of the zona glomerulosa and of resistance blood vessels with changes in the sodium state seem to be an effective and important means in the regulation of body sodium.