Faculty Bibliography

[Piero Anversa] said he never believed that the heart was an exception to the rule that cell regeneration is essential to life. Nor did he believe, as the dogma held, that scarring after heart attacks was evidence against the heart's ability to make new cells. Other organs, like the skin, constantly grow new cells to replace old and damaged ones and still leave scars, Anversa said. Anversa began this line of research 20 years ago. In its latest version his team compared muscle cells in the hearts of 13 patients who died four to 12 days after a large heart attack with those in the hearts of 10 patients who died from other causes. Anversa's team focused attention on two areas -- the zone of tissue bordering the site of a heart attack and from a more distant area of the heart. The findings still leave researchers seeking answers to a number of crucial questions about the origin of the new heart muscle cells Anversa identified. Were they cells in the heart that had been awakened after sleeping for years, even decades, only by the crisis of a heart attack? Or were the cells recruited from another site in the body in response to the heart attack?

Dr. Claude Lenfant, director of the National Heart Lung and Blood Institute, said [Piero Anversa]'s findings 'provide the most dramatic and clear-cut demonstration to date of heart cell regeneration after cardiac injury.' Anversa's findings add to those from studies on animals that show the dogma that the heart cannot regenerate 'is no longer true,' said Lenfant whose federal agency in Bethesda, Md., paid for the research conducted in Vallhala and at the University of Udine and University of Trieste in Italy. Lenfant also said he believes Anversa's research holds greater promise for heart disease than gene therapy, which many experts consider a highly promising route to new therapies

[Piero Anversa]'s findings add to those from studies on animals that show the dogma that the heart cannot regenerate 'is no longer true,' said [Claude J. Lenfant] whose federal agency in Bethesda, Md., paid for the research that was conducted in Valhalla and at the Universities of Udine and Trieste in Italy

[Piero Anversa]'s findings add to those from studies on animals that show the dogma that the heart cannot regenerate 'is no longer true,' said [Claude J. Lenfant] whose federal agency in Bethesda, Md., paid for the research that was conducted in Vallhala and at the University of Udine and University of Trieste in Italy. Lenfant said the findings eventually could have 'enormous public health value' if it led to new therapies that delayed the onset of heart failure and prolonged life. Lenfant also said that he believed Anversa's research holds greater promise for heart disease than gene therapy, which many experts consider a highly promising route to new therapies. Anversa said he never believed that the heart was an exception to the rule that cell regeneration is essential to life. Nor did he believe, as the dogma held, that scarring after heart attacks was evidence against the heart's ability to make new cells. Other organs, like the skin, constantly grow new cells to replace old and damaged ones and still leave scars, Anversa said

The new research, released Thursday, relies on a newer blood test to identify people who have been infected only recently. The researchers found that in the six cities, black gay men ages 23 to 29 had a 14.7% annual rate of new infection compared with 2.5% among white gay men and 3.5% among Hispanic gay men of the same age. For the age group overall, the new infection rate was 4.4%. Also, the study involved men who went to gay bars and similar venues, whose sexual practices and drug use may not mirror those of other gay men. On the other hand, the reluctance of many gay black men to acknowledge their homosexuality means their rate of HIV infection would not have been detected. The gay men in the study were small children in the 1980s when health officials issued the early information that helped reduce infection rates among gay men. Now, health officials say they must renew and sustain such messages in part because young gay men have not seen many friends die of AIDS and may not take prevention as seriously as older gays

The rate of new infections with HIV, the AIDS virus, among black gay men 23 to 29 years was six times that of a comparable group of young white gay men and three times that of all young gay men in the study. The study found that young black gay men had a 14.7% annual rate of new infection compared with 2.5% among young white gay men, 3.5% among Hispanic gay men and 4.4% for all gay men 23 to 29 years old. In February, the disease centers reported that among young gay black men the prevalence, or the total number of HIV infections and AIDS cases, was 30%. The new evidence shows that such infections occurred from 1998 to 2000. Although the number of infections could continue to rise, the findings do not necessarily mean that all would become infected in time because many of the uninfected are using recommended prevention measures

At a news conference, Dr. Helene D. Gayle, who directs the H.I.V. program at the Centers for Disease Control, and Dr. Linda Valleroy, who led the study, described the situation using similar terms, saying the ''explosive H.I.V. incidence rates'' were ''alarming'' and ''of critical public health importance.'' Also, the study involved men who went to gay bars and similar venues, whose sexual practices and drug use may not mirror those of other gay men. On the other hand, the reluctance of many gay black men to acknowledge their homosexuality means their rate of H.I.V. infection would not have been detected. In January, the Centers for Disease Control announced a new strategy that aims in part to encourage people at high risk to get an H.I.V. test and form a profile of those who are newly infected. The agency intends to use the information to tailor prevention and treatment efforts to the needs of infected gay men as part of the $400 million this year that the agency provides to state and local prevention programs. One aim will be to determine how such men can best be referred to health care and prevention services to reduce the risk of transmission. Because about half of those in the study said they engaged in unprotected anal sex, another goal will be to develop new and more effective prevention messages

The research released yesterday relies on a newer blood test to identify people who have been infected only recently. It found that in the six cities, black gay men 23 to 29 had a 14.7 percent annual rate of new infection compared with 2.5 percent among white gay men and 3.5 percent among Hispanic gay men of the same age. For the age group overall, the rate of new infection was 4.4 percent. To measure incidence, epidemiologists tested 2,942 volunteers, chosen at random in 194 urban neighborhoods, at dance clubs, bars and other public venues frequented by young gay men. The participants answered questions related to their sexual history and drug use and were counseled about HIV. Also, the study involved men who went to gay bars and similar venues, and their sexual practices and drug use may not mirror those of other gay men. On the other hand, the reluctance of many gay black men to acknowledge their homosexuality means their rate of HIV infection would not have been detected

Macrophages secrete matrix metalloproteinase 9 (MMP-9), an enzyme that weakens the fibrous cap of atherosclerotic plaques, predisposing them to plaque rupture and subsequent ischemic events. Recent work indicates that statins strongly reduce the possibility of heart attack. Furthermore, these compounds appear to exert beneficial effects not only by lowering plasma low-density-lipoprotein cholesterol but also by directly affecting the artery wall. To evaluate whether statins influence the proinflammatory responses of monocytic cells, we studied their effects on the chemotactic migration and MMP-9 secretion of human monocytic cell line THP-1. Simvastatin dose dependently inhibited THP-1 cell migration mediated by monocyte chemoattractant protein 1, with a 50% inhibitory concentration of about 50 nM. It also inhibited bacterial lipopolysaccharide-stimulated secretion of MMP-9. The effects of simvastatin were completely reversed by mevalonate and its derivatives, farnesylpyrophosphate and geranylgeranyl pyrophosphate, but not by ubiquinone. Additional studies revealed similar but more profound inhibitory effects with L-839,867, a specific inhibitor of geranylgeranyl transferase. However, alpha-hydroxyfarnesyl phosphonic acid, an inhibitor of farnesyl transferase, had no effect. C3 exoenzyme, a specific inhibitor of the prenylated small signaling Rho proteins, mimicked the inhibitory effects of simvastatin and L-839,867. These data supported the role of geranylgeranylation in the migration and MMP-9 secretion of monocytes.