Faculty Bibliography

Earlier devices were much larger and intended as a bridge to heart transplants. The titanium and plastic Abiomed device can be used only in patients who are near death from the failure of both of the natural heart's pumping chambers. It can be implanted only in people 18 and older who are ineligible for a transplant and whose life expectancy would be a month without it. The diseased heart is removed to make room for the two-pound, or 0.9 kilogram, device. Implanted, a coil transfers power across the skin and recharges the device from the outside. An internal battery and a controller that monitors and controls the heart rate are implanted in the abdomen. The approval on Tuesday followed an extensive review of the panel's concerns and discussions with Abiomed, agency officials said. A second advisory panel review was not warranted because of the talks with Abiomed, said Heidi Valetkevitch, a spokeswoman for the agency. No implants were performed while the petition to sell the device was under review

The titanium and plastic Abiomed device can be used only in patients who are near death from the failure of both of the natural heart's pumping chambers. It can be implanted only in people 18 and older who are ineligible for a transplant and whose life expectancy would be a month without it

The meeting, in Johannesburg on Thursday and Friday, comes in response to recent reports from a number of the world's regions about a small but growing number of cases of the deadly strains, known as extreme drug-resistant tuberculosis, or XDR-TB. Although the resistant strains have been identified in all regions of the world, especially Asia and the former Soviet Union, the immediate goal is to help South Africa control an outbreak that killed 52 of 53 patients in a rural province in recent months. The deaths occurred swiftly, on average within 25 days, and included patients who were taking antiretroviral drugs for H.I.V., the virus that causes AIDS. If the strain keeps spreading, it could exceed by ''hundreds of times'' the outbreak of drug-resistant tuberculosis in New York City in the 1990's, Dr. [Mario C. Raviglione] said. That outbreak was brought under control by adopting strong measures, including observation of infected patients to make sure they took their drugs properly

The titanium and plastic Abiomed device can be used just in patients who are near death from the failure of both of the natural heart's pumping chambers. The device can be implanted only in people 18 and older who are ineligible for a transplant and whose life expectancy would be a month without it. In June 2005, a panel of heart experts appointed to advise the F.D.A. voted, 7 to 6, against approving the Abiomed device, in part because of concern that the risks from complications like bleeding, strokes and infection outweighed the benefits. Some panel members expressed concern about whether patients would live long enough with an improved quality of life to justify the risks. Abiomed is aiming to keep patients alive 18 to 24 months with the device, primarily by selecting slightly healthier candidates for the implant. The company has a target of 2008 to introduce an improved design that is 30 percent smaller and intended to work for five years, Mr. [Michael R. Minogue] said

BACKGROUND: We studied female graduates of the Robert Wood Johnson Clinical Scholars Program (CSP, Class of 1984 to 1989) to explore and describe the complexity of creating balance in the life of mid-career academic woman physicians. METHODS: We conducted and qualitatively analyzed (kappa 0.35 to 1.0 for theme identification among rater pairs) data from a semi-structured survey of 21 women and obtained their curricula vitae to quantify publications and grant support, measures of academic productivity. RESULTS: Sixteen of 21 (76%) women completed the survey. Mean age was 48 (range: 45 to 56). Three were full professors, 10 were associate professors, and 3 had left academic medicine. Eleven women had had children (mean 2.4; range: 1 to 3) and 3 worked part-time. From these data, the conceptual model expands on 3 key themes: (1) defining, navigating, and negotiating success, (2) making life work, and (3) making work work. The women who described themselves as satisfied with their careers (10/16) had clarity of values and goals and a sense of control over their time. Those less satisfied with their careers (6/16) emphasized the personal and professional costs of the struggle to balance their lives and described explicit institutional barriers to fulfillment of their potential. CONCLUSION: For this group of fellowship-prepared academic women physicians satisfaction is achieving professional and personal balance

Thyroid hormone receptors (TRs), expressed as TRalpha1, TRbeta1, and TRbeta2 isoforms, are members of the steroid hormone nuclear receptor gene superfamily, which comprises ligand-dependent transcription factors. The TR isoforms differ primarily in their N-terminal (A/B) domains, suggesting that the A/B regions mediate distinct transcriptional activation functions in a cell type-dependent or promoter-specific fashion. The nuclear receptor ligand-binding domain (LBD) undergoes a conformational change upon ligand binding that results in the recruitment of coactivators to the LBD. For glucocorticoid receptor and estrogen receptor-alpha, the same coactivator can contact both the LBD and A/B domains, thus leading to enhanced transcriptional activation. Very little is known regarding the role of the A/B domains of the TR isoforms. The A/B domain of TRbeta2 exhibits higher ligand-independent transcriptional activity than the A/B regions of TRalpha1 or TRbeta1. Thus, we examined the role of the A/B domain and the LBD of rat TRbeta2 in integrating the transcriptional activation function of the A/B and LBD domains by different coactivators. Both domains are essential for a productive functional interaction with cAMP response element-binding protein (CREB)-binding protein (CBP), and we found that CBP binds to the A/B domain of TRbeta2 in vitro. In contrast, steroid receptor coactivator-1a (SRC-1a) interacts strongly with the LBD but not the A/B domain. The coactivator NRC (nuclear receptor coactivator) interacts primarily with the LBD, although a weak interaction with the A/B domain further enhances ligand-dependent binding with TRbeta2. Our studies document the interplay between the A/B domain and the LBD of TRbeta2 in recruiting different coactivators to the receptor. Because NRC and SRC-1a bind CBP, and CBP enhances ligand-dependent activity, our studies suggest a model in which coactivator recruitment of NRC (or SRC-1a) occurs primarily through the LBD whereas the complex is further stabilized through an interaction of CBP with the N terminus of TRbeta2

A CC chemokine, CCL18, has been previously reported to stimulate collagen production in pulmonary fibroblasts. This study focused on the role of protein kinase C (PKC) in the profibrotic signaling activated by CCL18 in pulmonary fibroblasts. Of the three PKC isoforms that are predominantly expressed in fibroblasts (PKCalpha, PKCdelta, and PKCepsilon), two isoforms (PKCdelta and PKCepsilon) have been implicated in profibrotic intracellular signaling. The role of PKCalpha-mediated signaling in the regulation of collagen production remains unclear. In this study, PKCalpha was found mostly in the cytoplasm, whereas PKCdelta and PKCepsilon were found mostly in the nucleus of cultured primary pulmonary fibroblasts. In response to stimulation with CCL18, PKCalpha but not PKCdelta or PKCepsilon underwent rapid (within 5-10 min) transient phosphorylation and nuclear translocation. Inhibition with dominant-negative mutants of PKCalpha and ERK2, but not PKCdelta or PKCepsilon, abrogated CCL18-stimulated ERK2 phosphorylation and collagen production. The effect of CCL18 on collagen production and the activity of collagen promoter reporter constructs were also abrogated by a selective pharmacologic inhibitor of PKCalpha Gö6976. Stimulation of fibroblasts with CCL18 caused an increase in intracellular calcium concentration. Consistent with the known calcium dependence of PKCalpha signaling, blocking of the calcium signaling with the intracellular calcium-chelating agent BAPTA led to abrogation of PKCalpha nuclear translocation, ERK2 phosphorylation, and collagen production. These observations suggest that in primary pulmonary fibroblasts, PKCalpha but not PKCdelta or PKCepsilon mediate the profibrotic effect of CCL18. PKCalpha may therefore become a viable target for future antifibrotic therapies.