Publications

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.

The cytokine transforming growth factor-beta (TGF-beta) is an important negative regulator of adaptive immunity. TGF-beta is secreted by cells as an inactive precursor that must be activated to exert biological effects, but the mechanisms that regulate TGF-beta activation and function in the immune system are poorly understood. Here we show that conditional loss of the TGF-beta-activating integrin alpha(v)beta8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of alpha(v)beta8 on dendritic cells, as mice lacking alpha(v)beta8 principally on dendritic cells develop identical immunological abnormalities as mice lacking alpha(v)beta8 on all leukocytes, whereas mice lacking alpha(v)beta8 on T cells alone are phenotypically normal. We further show that dendritic cells lacking alpha(v)beta8 fail to induce regulatory T cells (T(R) cells) in vitro, an effect that depends on TGF-beta activity. Furthermore, mice lacking alpha(v)beta8 on dendritic cells have reduced proportions of T(R) cells in colonic tissue. These results suggest that alpha(v)beta8-mediated TGF-beta activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of alpha(v)beta8 on dendritic cells to induce and/or maintain tissue T(R) cells.

Occult hepatitis B virus (HBV) infection is of concern in human immunodeficiency virus (HIV)-infected persons. We observed that 2% of 400 HIV-infected women with antibodies to hepatitis B core antigen alone had occult HBV infection (i.e., detectable HBV DNA in the absence of HBV surface antigen). CD4 cell counts of <200 cells/mm3 were more common among occult HBV-infected women than among those without occult HBV infection. Aminotransferase levels did not appear to be associated with being positive for HBV DNA.