Dissolution of particulate hydroxyapatite in a macrophage organelle model

The optimum 14N pulse lengths in the 13C-14N rotational-echo adiabatic-passage double-resonance (REAPDOR) NMR experiment are determined from calculations and from experiments on samples of glycine and L-alanine. The REAPDOR experiment utilizes the adiabatic passages that 14N spins make between the 14N Zeeman energy levels during the application of a single, short 14N radiofrequency pulse. Use of a short 14N irradiation time of less than one-quarter of a rotor period ensures that the number of 14N spins that undergo more than one passage is minimized. This simplifies calculations describing 13C dipolar dephasing and provides better agreement between calculations and experiments. Recovery of the 13C-14N dipolar couplings and 14N quadrupolar coupling constants and asymmetry parameters is described.     

Cancer incidence and mortality: the priority of screening frequency and population coverage

In addition to the usual measures of screening-test performance, it is important to consider testing frequency when evaluating a screening program. Data on which to base recommendations for the timing of screening tests are urgently needed. For example, in the cases of cervical and colon cancer, when the target is a precursor lesion, research indicates that less frequent screening may be appropriate. This finding may not apply, however, to screening for breast cancer by mammography, which requires currently recommended intervals for the early detection of malignancies. Resources now allocated to breast cancer might more effectively be applied to the construction of tests that would permit longer intervals between screenings. To achieve the National Cancer Institute's goal of reducing cancer mortality in the United States by the year 2000, it will be important to review the balance between population coverage and individual screening for each cancer and to emphasize prevention strategies that maximize population coverage while minimizing expenditures.     

Importance of the 'crossover' concept in exercise metabolism

1. The 'crossover' concept is a model of substrate supply during exercise which makes the following predictions. 2. Lipid is the major fuel (approximately 60%) for non-contracting skeletal muscle and the body at rest. 3. Energy flux, as determined by exercise intensity, is the major factor in determining the balance of substrate utilization during exercise. Thus, moderate and greater exercise intensities increase contraction-induced muscle glycogenolysis and glycolysis, increase recruitment of fast-twitch muscle fibres, increase sympathetic nervous system activity and down-regulate mitochondrial fatty acid uptake. 4. Glycogen and glucose utilization scales exponentially to relative exercise power output with a greater gain in glycogen than in glucose use at high power. The relationship between free fatty acid flux and power output is an inverted hyperbola. Consequently, at high power outputs, the role of lipid oxidation is diminished. 5. Factors such as endurance training, energy supply, as influenced by dietary manipulation, and prior exercise play secondary roles in determining the balance of substrate utilization during exercise. 6. Comparisons of the metabolic responses in subjects engaged in activities requiring vastly different metabolic rates or comparisons of subjects of different gender, age or training status require normalization of data to total energy flux.     

delta-9-Tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of Bacillus Calmétte-Guérin-activated macrophages

The effect of delta-9-tetrahydrocannabinol (delta-9-THC), the major psychoactive component of marijuana, on the capacity of Bacillus Calmétte-Guérin (BCG)-activated macrophages to lyse L929 tumor cells, Naegleria fowleri amoebae, and herpes simplex virus-infected cells was examined. Delta-9-THC inhibited tumoricidal and amoebicidal activity in a dose-related manner. Antiviral activity was decreased when mice received 25 and 50 mg/kg delta-9-THC. The cannabinoid did not directly suppress the activation of macrophages as determined by levels of 5'-nucleotidase activity and did not inhibit splenic T-lymphocytes of BCG-recipient mice from producing interferon gamma. Nomarski optics microscopy, scanning electron microscopy, and radiolabeling binding studies demonstrated that macrophages from delta-9-THC-treated mice retained their capacity to attach to their targets. These results suggest that delta-9-THC suppresses cell contact-dependent amoebicidal, tumoricidal, and antiviral activities of activated macrophages at a stage following effector cell-target cell conjugation.