Publications

The University of California, San Francisco (UCSF) established Global Health Sciences (GHS) as a campus-wide initiative in 2003. The mission of GHS is to facilitate UCSF's engagement in global health across its four schools by (1) creating a supportive environment that promotes UCSF's leadership role in global health, (2) providing education and training in global health, (3) convening and coordinating global health research activities, (4) establishing global health outreach programs locally in San Francisco and California, (5) partnering with academic centers, especially less-well-resourced institutions in low- and middle-income countries, and (6) developing and collaborating in international initiatives that address neglected global health issues.GHS education programs include a master of science (MS) program expected to start in September 2008, an introduction to global health for UCSF residents, and a year of training at UCSF for MS and PhD students from low- and middle-income countries that is "sandwiched" between years in their own education program and results in a UCSF Sandwich Certificate. GHS's work with partner institutions in California has a preliminary focus on migration and health, and its work with academic centers in low- and middle-income countries focuses primarily on academic partnerships to train human resources for health. Recognizing that the existing academic structure at UCSF may be inadequate to address the complexity of global health threats in the 21st century, GHS is working with the nine other campuses of the University of California to develop a university-wide transdisciplinary initiative in global health.

People with HIV infection have metabolic abnormalities that resemble metabolic syndrome (hypertriglyceridemia, low high-density lipoprotein cholesterol, and insulin resistance), which is known to predict increased risk of cardiovascular disease (CVD). However, there is not one underlying cause for these abnormalities and they are not linked to each other. Rather, individual abnormalities can be affected by the host response to HIV itself, specific HIV drugs, classes of HIV drugs, HIV-associated lipoatrophy, or restoration to health. Furthermore, one component of metabolic syndrome, increased waist circumference, occurs less frequently in HIV infection. Thus, HIV infection supports the concept that metabolic syndrome does not represent a syndrome based on a common underlying pathophysiology. As might be predicted from these findings, the prevalence of CVD is higher in people with HIV infection. It remains to be determined whether CVD rates in HIV infection are higher than might be predicted from traditional risk factors, including smoking.

The pro-opiomelanocotin (POMC) plays a key role in body weight regulation, where its derived peptides mediate leptin action via the hypothalamic melanocortin 4 receptor (MC4R). The pathogenic effects of POMC mutations have been challenged in obesity. Our aim was to assess the relevance of POMC mutations in a cohort of French obese and nonobese children. Direct sequencing of the POMC gene was performed in 322 obese and 363 control unrelated children. Functional studies for the novel Phe144Leu mutation included the response to alpha-melanocyte stimulating hormone (alphaMSH) and a competitive binding assay. POMC mutations were identified in 3.72% of obese [95% confidence interval (CI): 1.66-5.80] and 2.20% of control (95% CI: 0.69-3.71) subjects. The novel mutation located in the alphaMSH region of the POMC gene (Phe144Leu) was found in one obese child and was transmitted by the obese father. Functional studies showed that MC4R activation in response to Leu144alphaMSH was almost completely abolished due to a dramatically altered binding of Leu144alphaMSH to MC4R. The frequency of POMC mutations is not significantly different between obese and control children in our cohort. The novel heterozygous mutation Phe144Leu leading to the absence of melanocortin signaling was associated with early-onset obesity suggesting its pathogenic role.