Publications

This paper examined the effects of socioenvironmental and personal factors on two stages of the smoking continuum--onset of smoking and regular smoking--among a sample of 1411 Latina clients, ages 14-24, at two federally funded family planning clinics. The socioenvironmental factors included cultural indicators, smoking behavior of family and peers, and norms. The personal factors were risk-taking behaviors and intention to smoke in the future. Results showed that the indicators associated with experimentation were different than those linked with regular smoking. Socioenvironmental factors associated with the transition from never having smoked to trying cigarettes included acculturation, as measured by language and familialism, and peer smoking behavior. Among the personal factors, risk-taking behavior (past use of drugs, alcohol, and general risk attitude) and smoking intentions were correlates of experimentation. The transition from experimenter to regular smoker was associated with peer smoking behavior (P< .05) in the socioenvironmental domain and drug use and intention to smoke in the future among the personal factors (both P values <.001). Age, years of education, marital status, norms, and parental smoking did not independently predict either of the smoking outcomes. Intention to smoke was the strongest predictor of experimentation (OR = 8.3, Cl 5.87-11.60) and regular smoking (OR= 19.9, CI 12.31-29.21) and could help identify those most likely to benefit from smoking prevention and cessation interventions.

Anxiety following an abnormal mammogram result can be substantial. We examined whether the time to the first diagnostic test was associated with anxiety. We surveyed 449 women at 2 and 8 months after an abnormal mammogram result, and we reviewed their medical records. Twenty-six percent of women reported being very anxious about their abnormal mammogram result at the time of the two-month interview, and 22% reported persistent anxiety after 8 months. After adjustment, the number of days until the first diagnostic test was not associated with anxiety at the 2-month interview. By the second interview, women who received their first diagnostic test within the first week were significantly more anxious, as were women who did not receive their first test for at least 60 days after their results. Further work is needed to ascertain how to minimize the anxiety associated with the evaluation of an abnormal mammogram.

BACKGROUND

The polyene macrolide amphotericin B is produced by Streptomyces nodosus ATCC14899. Amphotericin B is a potent antifungal antibiotic and has activity against some viruses, protozoans and prions. Treatment of systemic fungal infections with amphotericin B is complicated by its low water-solubility and side effects which include severe nephrotoxicity. Analogues with improved properties could be generated by manipulating amphotericin biosynthetic genes in S. nodosus.

RESULTS

A large polyketide synthase gene cluster was cloned from total cellular DNA of S. nodosus. Nucleotide sequence analysis of 113193 bp of this region revealed six large polyketide synthase genes as well as genes for two cytochrome P450 enzymes, two ABC transporter proteins, and genes involved in biosynthesis and attachment of mycosamine. Phage KC515-mediated gene disruption was used to show that this region is involved in amphotericin production.

CONCLUSIONS

The availability of these genes and the development of a method for gene disruption and replacement in S. nodosus should allow production of novel amphotericins. A panel of analogues could lead to identification of derivatives with increased solubility, improved biological activity and reduced toxicity.

Extracellular matrix (ECM) remodeling is critical to morphogenesis and homeostasis. The identification of inactivating mutations in a gene encoding one of its modifying enzymes, matrix metalloproteinase 2 (MMP-2), in people with a hereditary disorder in which the bones disintegrate, represents the first genetic evidence that the proteolysis of the ECM mediates human growth and development. It also underscores the need for an intricate balance between breakdown and deposition of the ECM.

The integrin alphavbeta6 is restricted to epithelial cells and is dramatically induced in response to injury and inflammation. Mice expressing a null mutation of this integrin develop exaggerated inflammation of the lungs and skin, but are dramatically protected from bleomycin-induced pulmonary fibrosis. This phenotype led to the identification of a unique role for this integrin in binding to and activating latent extracellular complexes of the anti-inflammatory, profibrotic cytokine, transforming growth factor-beta(1). This integrin-mediated activation is tightly spatially restricted and appears to require direct presentation of the activated cytokine to receptors on adjacent cells. The process also requires distinct regions of the beta6-subunit cytoplasmic domain and an intact actin cytoskeleton, suggesting the existence of additional cellular mechanisms to regulate this process. If this mechanism is found to be as important in humans as it is in mice, the integrin and as yet to be identified pathways for cellular regulation of this process could be exciting new targets for intervention in fibrotic diseases of the lung and other epithelial organs.

The integrin alphavbeta6 is a fibronectin receptor whose expression is not detectable on normal oral epithelium but is increased significantly in healing and in oral epithelial dysplasia and oral squamous cell carcinoma, suggesting it may promote changes associated with tumor development. To study whether alphavbeta6 may drive invasive behavior we have used transfection and retroviral infection to create a panel of epithelial cell lines expressing various levels of alphavbeta6. We report that increased expression of alphavbeta6 in malignant keratinocytes promotes invasion and leads to an increased capacity for migration towards fibronectin. alphavbeta6 expression may have a significant role in contributing to the malignant behavior of epithelial cells.