Heart period variability of trained and untrained men at rest and during mental challenge

The effect of aerobic training on parasympathetic reactivity to mental stress is unclear. Thus, the parasympathetic response, as assessed by time series analysis of heart period variability (HPV_ts), of 10 trained male runners (trained group), 10 inherently low resting heart rate untrained men (low HR group), and 10 normal resting HR men (control group) at rest and to two mental stressors was examined. Participants completed a mental arithmetic and Stroop task. Resting HPV_ts at high and medium frequencies was significantly greater for the trained and the low HR groups than for the control group. Significantly greater decreases in HPV_ts at the medium frequency during arithmetic recovery were measured for the trained and low HR groups compared with the response of the control group. Significantly greater decreases in HPV_ts at both the the high and medium frequencies during the first two epochs of the Stroop occurred only for the trained and low HR groups. These results suggest that the greater HPV_ts at rest and decline in HPV_ts during and after mental challenge is influenced by both aerobic training and genetic inheritance.     

Cdc13 both positively and negatively regulates telomere replication

Cdc13 is a single-strand telomeric DNA-binding protein that positively regulates yeast telomere replication by recruiting telomerase to chromosome termini through a site on Cdc13 that is eliminated by the cdc13-2 mutation. Here we show that Cdc13 has a separate role in negative regulation of telomere replication, based on analysis of a new mutation, cdc13-5. Loss of this second regulatory activity results in extensive elongation of the G strand of the telomere by telomerase, accompanied by a reduced ability to coordinate synthesis of the C strand. Both the cdc13-5 mutation and DNA polymerase alpha mutations (which also exhibit elongated telomeres) are suppressed by increased expression of the Cdc13-interacting protein Stn1, indicating that Stn1 coordinates action of the lagging strand replication complex with the regulatory activity of CDC13. However, the association between Cdc13 and Stn1 is abolished by cdc13-2, the same mutation that eliminates the interaction between Cdc13 and telomerase. We propose that Cdc13 participates in two regulatory steps-first positive, then negative-as a result of successive binding of telomerase and the negative regulator Stn1 to overlapping sites on Cdc13. Thus, Cdc13 coordinates synthesis of both strands of the telomere by first recruiting telomerase and subsequently limiting G-strand synthesis by telomerase in response to C-strand replication.     

Candidacidal factors in murine bronchoalveolar lavage fluid.

Respiratory secretions provide an efficient method for protecting the large surface area of the lower respiratory tract. To determine whether lung secretions contribute to antifungal defenses, we tested bronchoalveolar lavage fluid for fungicidal activity. Candida albicans (blastoconidia) was incubated in unconcentrated cell-free lavage fluid from Swiss Webster mice and then cultured quantitatively to measure residual viability. In control buffer the residual fractions of viable fungi were 1.03 +/- 0.12 at 60 min and 0.84 +/- 0.05 at 120 min, whereas the residual fractions in lavage fluid were 0.64 +/- 0.07 and 0.23 +/- 0.05, respectively (P less than 0.05 by t tests). This activity was trypsin sensitive and heat stable (56 degrees C) and did not require divalent cations. It did not sediment with the surfactant fraction of lung lavage fluid. Unconcentrated lavage fluid reduced the adherence of C. albicans to serum-coated glass tubes to 2.3 +/- 1.5% of that of control Candida suspensions (n = 5, P less than 0.05 by t test). It did not alter Candida ingestion or intracellular processing by alveolar macrophages. Lavage fluid also killed clinical isolates of Candida tropicalis and Torulopsis glabrata but did not kill Candida krusei or Candida parapsilosis. Lavage fluid was concentrated and passed through an acrylamide-agarose gel matrix. The chromatogram indicated that the candidacidal activity eluted in a peak with a molecular weight range of 29,000 to 40,000. After electrophoresis on 15% sodium dodecyl sulfate-polyacrylamide gels, these fractions resolved into three bands. These were transferred to nitrocellulose and then eluted with Triton X-100; this procedure permitted the isolation of a single band of candidacidal activity with a molecular weight of 29,000. In summary, murine lavage fluid contains a heat-stable protein with direct antifungal activity. This soluble factor may contribute to lung defense processes by reducing fungal viability and adherence to tissue surfaces.     

Benchmarking cardiac surgery: a regional initiative to improve outcomes. Interview by Reggi Veatch

Many of the clinical benchmarking projects featured in the Lead Story are designed to produce quick results. The Northern New England Cardiovascular Disease Study Group (NNE), by contrast, is a long-term effort to improve patients' functional health status. Formed in 1987, NNE is a voluntary consortium comprising all providers of open heart surgery in Maine, New Hampshire, and Vermont--five facilities and 28 surgeons. Although NNE is just beginning to focus on best practices within the region, its early benchmarking efforts have produced a collaborative environment in which clinical information is now readily shared. Because of this, its accomplishments have been striking: the creation of a database that includes information on more than 18,000 patients; the development of a highly accurate mortality prediction tool for patients facing coronary bypass surgery; and a 24 percent decrease in regional operative mortality following coronary artery bypass graft (CABG) surgery.     

Hyperglycemia,Insulin, and Insulin Resistance in Sepsis

Critically ill patients frequently have hyperglycemia. This event may reflect severe stress with an imbalance between anabolic hormones and catabolic hormones. Alternatively, it may reflect alterations in either insulin levels or insulin function. Insulin is a pleiotropic hormone with multiple important metabolic effects. In patients with sepsis, insulin levels are increased but insulin sensitivity is decreased. However, there is variability in insulin sensitivity, and this creates variability in glucose levels and insulin requirements and increases the frequency of hypo- and hyperglycemia. The factors that influence insulin sensitivity are complex and include inhibition of tyrosine kinase activity of the beta subunit, increased proteolytic activity resulting in loss of receptors from the plasma membrane, and possibly the transfer of insulin receptors into the nucleus where they bind to gene promoters. Better understanding of the role of insulin in critically ill patients requires prospective studies measuring insulin levels in various patient groups and the development of a simple measure of insulin sensitivity.