Publications

Mycobacterium tuberculosis (Mtb) is thought to reside in macrophages, although infected dendritic cells (DCs) have been observed. Thus, although cellular associations have been made, global characterization of the cells harboring Mtb is lacking. We have performed temporal and quantitative characterization of the cells harboring Mtb following aerosol infection of mice by using GFP-expressing bacteria and flow cytometry. We discovered that Mtb infects phagocytic cells of diverse phenotypes, that the predominant infected cell populations change with time, and that myeloid DCs are the major cell population infected with Mtb in the lungs and lymph nodes. We also found that the bacteria in the lung-draining lymph node are transported there from the lungs by a CCL19/21-dependent mechanism and that the transport of bacteria to the lymph node is a transient phenomenon despite chronic infection. In addition, we found that the lymph node cell subsets that are most efficacious in stimulating Mtb-specific, TCR-transgenic CD4(+) T lymphocytes are not infected with the bacteria and are scarce or absent from the lungs of infected mice. Finally, we found that the lung cell populations that are infected with Mtb at high frequency are relatively ineffective at stimulating Ag-specific CD4(+) T lymphocytes, and we have obtained evidence that live Mtb can inhibit MHC class II Ag presentation without a decrease in the surface expression of MHC class II. These results indicate that Mtb targets DC migration and Ag presentation in vivo to promote persistent infection.

We investigated the ability of pyrroloquinoline quinone (PQQ) to confer resistance to acute oxidative stress in freshly isolated adult male rat cardiomyocytes. Fluorescence microscopy was used to detect generation of reactive oxygen species (ROS) and mitochondrial membrane potential (Deltapsi(m)) depolarization induced by hydrogen peroxide. H(2)O(2) caused substantial cell death, which was significantly reduced by preincubation with PQQ. H(2)O(2) also caused an increase in cellular ROS levels as detected by the fluorescent indicators CM-H2XRos and dihydroethidium. ROS levels were significantly reduced by a superoxide dismutase mimetic Mn (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or by PQQ treatment. Cyclosporine-A, which inhibits mitochondrial permeability transition, prevented H(2)O(2)-induced Deltapsi(m) depolarization, as did PQQ and MnTBAP. Our results provide direct evidence that PQQ reduces oxidative stress, mitochondrial dysfunction, and cell death in isolated adult rat cardiomyocytes. These findings provide new insight into the mechanisms of PQQ action in the heart.

OBJECTIVES

To determine whether the association between self-rated health (SRH) and 4-year mortality differs between black and white Americans and whether education affects this relationship.

DESIGN

Prospective cohort.

SETTING

Communities in the United States.

PARTICIPANTS

Sixteen thousand four hundred thirty-two subjects (14,004 white, 2,428 black) enrolled in the 1998 wave of the Health and Retirement Study (HRS), a population-based study of community-dwelling U.S. adults aged 50 and older.

MEASUREMENTS

Subjects were asked to self-identify their race and their overall health by answering the question, "Would you say your health is excellent, very good, good, fair, or poor?" Death was determined according to the National Death Index.

RESULTS

SRH is a much stronger predictor of mortality in whites than blacks (c-statistic 0.71 vs 0.62). In whites, poor SRH resulted in a markedly higher risk of mortality than excellent SRH (odds ratio (OR)=10.4, 95% confidence interval (CI)=8.0-13.6). In blacks, poor RSH resulted in a much smaller increased risk of mortality (OR=2.9, 95% CI=1.5-5.5). SRH was a stronger predictor of death in white and black subjects with higher levels of education, but differences in education could not account for the observed race differences in the prognostic effect of SRH.

CONCLUSION

This population-based study found that the relationship between SRH and mortality is stronger in white Americans and in subjects with higher levels of education. Because the association between SRH and mortality appears weakest in traditionally disadvantaged groups, SRH may not be the best measure to identify vulnerable older subjects.