Publications

Reversible airway hyperreactivity underlies the pathophysiology of asthma, yet the precise mediators of the response remain unclear. Human studies have correlated aberrant activation of T helper (Th) 2-like effector systems in the airways with disease. A murine model of airway hyperreactivity in response to acetylcholine was established using mice immunized with ovalbumin and challenged with aerosolized antigen. No airway hyperractivity occurred in severe combined immunodeficient mice. Identically immunized BALB/c mice developed an influx of cells, with a predominance of eosinophils and CD4+ T cells, into the lungs and bronchoalveolar lavage fluid at the time that substantial changes in airway pressure and resistance were quantitated. Challenged animals developed marked increases in Th2 cytokine production, eosinophil influx, and serum immunoglobulin E levels. Neutralization of interleukin (IL) 4 using monoclonal antibodies administered during the period of systemic immunization abrogated airway hyperractivity but had little effect on the influx of eosinophils. Administration of anti-IL-4 only during the period of the aerosol challenge did not affect the subsequent response to acetylcholine. Finally, administration of anti-IL-5 antibodies at levels that suppressed eosinophils to < 1% of recruited cells had no effect on the subsequent airway responses. BALB/c mice had significantly greater airway responses than C57BL/6 mice, consistent with enhanced IL-4 responses to antigen in BALB/c mice. Taken together, these data implicate IL-4 generated during the period of lymphocyte priming with antigen in establishing the cascade of responses required to generate airway hyperractivity to inhaled antigen. No role for IL-5 or eosinophils could be demonstrated.

This paper examines adherence to a referral for a screening mammogram among an ethnically diverse sample of 576 female county health department patients age 50 and over. Data were obtained by interview approximately one year after the referral for a screening mammogram. Overall, approximately 80% of the sample were adherent to the referral. Medical record validation of self-reports of mammography receipt verified receipt of a mammogram for 82% of those reporting one. In logistic regression analysis, determinants of adherence included: transportation barriers, fear of immigration authorities, perceived control over getting breast cancer, self-rated health status, age, and perceived quality of provider-patient communication. The most prevalent concerns about mammography were concern over finding cancer, treatment for breast cancer, and removal of a breast. Reporting of these concerns was not significantly related to adherence. Also reported are barriers to health care experienced by this population over the past 12 months. The high adherence rate found in this study emphasizes the importance of provider referral in the delivery of screening mammography, and invalidates assumptions that women of lower education and lower income are less likely to adhere to provider recommendations.

In the last decade, numerous research and programmatic efforts have attempted to improve cancer screening practices among women from diverse race/ethnic backgrounds on the assumption that observed differences in breast cancer survival were largely due to differences in early detection practices. Recent data from the 1992 National Health Interview Survey and a 1992 survey in San Francisco Bay Area multiethnic communities indicate that rates of self-reported breast cancer screening tests among African American, Hispanic, and white women no longer differ significantly. However, there are large, persistent socioeconomic differences as reflected in educational and income levels, the recency of immigration, and English language proficiency. This emphasizes the continuing need for interventions tailored specifically for the underserved, with the racial, ethnic, and cultural composition of the intended audience informing educational messages and strategies. However, effective research interventions are complex and costly throughout the spectrum of outreach, inreach, and follow-up. Thus the generalizability of these strategies to under-founded providers and agencies in low-income communities may be limited. Therefore, as ongoing research continues to refine strategies, the application of effective community-based intervention should seek out potential partnerships with programs that provide the critical access to services. Cancer control scientists are well positioned to advocate for community-based infrastructures that facilitate translation of research into practice.

The human T-cell leukemia virus type I (HTLV-I) has been etiologically associated with the development of the adult T-cell leukemia (ATL) as well as degenerative neurologic syndrome termed tropical spastic paraparesis (TSP). HTLV-I encodes a potent transactivator protein termed Tax that appears to play an important role in the process of T-cell immortalization. Even though the mechanisms by which Tax induces transformation are still unknown, it seems likely that the ability of Tax to alter the expression of many cellular genes plays an important part in this process. Tax does not bind directly to DNA but rather deregulates the activity of cellular transcription factors. One family of host transcription factors whose activity is altered by Tax includes NF-kappa B/Rel. These transcription factors are post-transcriptionally regulated by their assembly with a second family of inhibitory proteins termed I kappa B that serve to sequester the NF-kappa B/Rel complexes in the cytoplasm. Upon cellular activation, I kappa B alpha is phosphorylated, polyubiquitinated, and degraded in the proteasome. This proteolytic event liberates NF-kappa B, permitting its rapid translocation into the nucleus where it binds to its cognate enhancer elements. Similarly, the p105 precursor of the NF-kappa B p50 subunit is also post-translationally processed in the proteasome. The mechanisms by which Tax activates NF-kappa B remain unclear, and findings presented in the literature are often controversial. We identified a physical interaction between Tax and the HsN3 subunit of the human proteasome. This raises the intriguing possibility that physical association of the HsN3 proteasome subunit with HTLV-I Tax coupled with the independent interaction of Tax with either p100 or p65-I kappa B alpha targets these cytoplasmic NF-kappa B/Rel complexes to the proteasome for processing.

Methodological advances now permit human biologists to more effectively monitor energy dynamics in traditional societies. This study examines the nutritional ecology and energetics of semisubsistence herders of Siberia (Evenki) during a single season of their annual cycle (late summer). Total energy expenditure (TEE) among adults, as measured by daily heart-rate monitoring, is greater in Evenki men (TEE = 11.9 ± 2.8 MJ/d in men and 8.8 ± 2.1 MJ/d in women; P < 0.001), a pattern that reflects the current division of labor under collectivized herding systems. Energy intakes are also greater among men (13.4 ± 5.6 vs. 8.5 ± 3.4 MJ/d; P < 0.01), and are, on average, sufficient to meet daily needs in both sexes. The Evenki appear to be in energy balance at the population level during the late summer (per capita energy intake = 9.0 ± 5.5 MJ/person/d; per capita requirements = 8.6 MJ/person/d); however, only small changes in food availability and/or energy expenditure are necessary to shift the population into negative balance during the winter. Primary sources of dietary energy include reindeer meat and other animal products (25-30%), foraged plant foods (10-15%), and nonlocal products (55-65%), such as flour, rice, and sugar. The anthropometric data indicate that the Evenki grow slowly and have small adult body size. Women are relatively heavier and fatter than men, and show a centripetal pattern of fat distribution. Evenki males appear to be undergoing a secular trend in stature, while no such increases are evident in females. These gender differences may reflect the differential impact to the changes associated with collectivization. Reduced metabolic requirements (due to declining activity and fertility levels), along with greater food availability, are likely to be responsible for the higher rates of obesity among Evenki women. © 1996 Wiley-Liss, Inc.