Publications

To make sound health care decisions, policy makers, providers and researchers need access to relevant research findings. The role of systematic reviews is increasingly acknowledged as an important contribution in evidence-based health care decision making, and several review efforts, including that of the international Cochrane Collaboration, are under way. The Cochrane Collaborative Review Group on HIV Infection and AIDS (CRG on HIV/AIDS), conducts systematic reviews on the prevention and the treatment of HIV infection and AIDS and is guided by the Cochrane Collaboration's principles, which include minimizing potential bias, ensuring quality in the review process, keeping reviews up to date, and enhancing collaboration. The CDC HIV/AIDS Prevention Research Synthesis (PRS) project is working closely with the CRG on HIV/AIDS to produce Cochrane reviews of behavioral prevention interventions and on development and maintenance of a centralized, cumulative electronic database of HIV/AIDS behavioral prevention studies. Systematic reviews can play an important role in advancing evidence-based policy and practice in HIV/AIDS prevention and care.

Adequate control of HIV requires impairing the infection, replication and spread of the virus, no small task given the extraordinary capacity of HIV to exploit the cell's molecular machinery in the course of infection. Understanding the dynamic interplay of host cell and virus is essential to the effort to eradicate HIV.

Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes the enzyme cholesterol 7alpha-hydroxylase, which catalyzes the initial step in cholesterol catabolism and bile acid synthesis. We report here a new metabolic disorder presenting with hyperlipidemia caused by a homozygous deletion mutation in CYP7A1. The mutation leads to a frameshift (L413fsX414) that results in loss of the active site and enzyme function. High levels of LDL cholesterol were seen in three homozygous subjects. Analysis of a liver biopsy and stool from one of these subjects revealed double the normal hepatic cholesterol content, a markedly deficient rate of bile acid excretion, and evidence for upregulation of the alternative bile acid pathway. Two male subjects studied had hypertriglyceridemia and premature gallstone disease, and their LDL cholesterol levels were noticeably resistant to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. One subject also had premature coronary and peripheral vascular disease. Study of the kindred, which is of English and Celtic background, revealed that individuals heterozygous for the mutation are also hyperlipidemic, indicating that this is a codominant disorder.

Population variability in nasal irritant (chemesthesic) sensitivity has been postulated by both clinicians and epidemiologists studying indoor and ambient air pollution. Among experimentalists, however, limited attention has been paid to variance in this trait. Candidate susceptibility markers include age, gender, presence or absence of nasal allergies or olfactory dysfunction, cognitive bias and self-reported pollutant reactivity. For most of these markers, conflicting data exist. This review distinguishes between functional subcomponents of nasal irritant sensitivity (sensory acuity versus physiologic reactivity), catalogs psychophysical and physiological methods for their study and examines the current evidence for variation in this trait. In general, interindividual variability has been an under-studied phenomenon.

Asthma is an increasingly common disease that remains poorly understood and difficult to manage. This disease is characterized by airway hyperreactivity (AHR, defined by exaggerated airflow obstruction in response to bronchoconstrictors), mucus overproduction and chronic eosinophilic inflammation. AHR and mucus overproduction are consistently linked to asthma symptoms and morbidity. Asthma is mediated by Th2 lymphocytes, which produce a limited repertoire of cytokines, including interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Although each of these cytokines has been implicated in asthma, IL-13 is now thought to be especially critical. In animal models of allergic asthma, blockade of IL-13 markedly inhibits allergen-induced AHR, mucus production and eosinophilia. Furthermore, IL-13 delivery to the airway causes all of these effects. IL-13 is thus both necessary and sufficient for experimental models of asthma. However, the IL-13-responsive cells causing these effects have not been identified. Here we show that mice lacking signal transducer and activator of transcription 6 (STAT6) were protected from all pulmonary effects of IL-13. Reconstitution of STAT6 only in epithelial cells was sufficient for IL-13-induced AHR and mucus production in the absence of inflammation, fibrosis or other lung pathology. These results demonstrate the importance of direct effects of IL-13 on epithelial cells in causing two central features of asthma.