Receptor-Mediated Recognition and Uptake of Iron from Human Transferrin by Staphylococcus aureus and Staphylococcus epidermidis

Staphylococcus aureus and Staphylococcus epidermidis both recognize and bind the human iron-transporting glycoprotein, transferrin, via a 42-kDa cell surface protein receptor. In an iron-deficient medium, staphylococcal growth can be promoted by the addition of human diferric transferrin but not human apotransferrin. To determine whether the staphylococcal transferrin receptor is involved in the removal of iron from transferrin, we employed 6 M urea–polyacrylamide gel electrophoresis, which separates human transferrin into four forms (diferric, monoferric N-lobe, and monoferric C-lobe transferrin and apotransferrin). S. aureus and S. epidermidis but not Staphylococcus saprophyticus (which lacks the transferrin receptor) converted diferric human transferrin into its apotransferrin form within 30 min. During conversion, iron was removed sequentially from the N lobe and then from the C lobe. Metabolic poisons such as sodium azide and nigericin inhibited the release of iron from human transferrin, indicating that it is an energy-requiring process. To demonstrate that this process is receptor rather than siderophore mediated, we incubated (i) washed staphylococcal cells and (ii) the staphylococcal siderophore, staphyloferrin A, with porcine transferrin, a transferrin species which does not bind to the staphylococcal receptor. While staphyloferrin A removed iron from both human and porcine transferrins, neither S. aureus nor S. epidermidis cells could promote the release of iron from porcine transferrin. In competition binding assays, both native and recombinant N-lobe fragments of human transferrin as well as a naturally occurring human transferrin variant with a mutation in the C-lobe blocked binding of ¹²⁵I-labelled transferrin. Furthermore, the staphylococci removed iron efficiently from the iron-loaded N-lobe fragment of human transferrin. These data demonstrate that the staphylococci efficiently remove iron from transferrin via a receptor-mediated process and provide evidence to suggest that there is a primary receptor recognition site on the N-lobe of human transferrin.     

Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis

Recent studies demonstrate that the receptor tyrosine kinase (TK) Ron is tumorigenic when overexpressed and plays a role in regulating skin homeostasis. We hypothesized that Ron signaling promotes skin carcinogenesis. To test this hypothesis, mice deficient in the TK domain of Ron (TK(-/-) mice) were crossed with v-Ha-ras (Tg.AC) transgenic mice; the resulting TK(-/-) Tg.AC(+/-) mice, and their controls, were utilized in a model of chemically induced Ras-mediated skin carcinogenesis. The mice were treated with 2.5 microg of 12-O-tetradecanoylphorbol-13-acetate applied weekly to the shaved back of 36 control (TK(+/+) Tg.AC(+/-)) and 35 experimental (TK(-/-) Tg.AC(+/-)) mice. In an analysis of the resulting papillomas, a reduction in cellular proliferation and papilloma volume was found in the TK(-/-) Tg.AC(+/-) mice compared to controls. Further, Ron protein expression was upregulated during papilloma formation. Ablation of Ron signaling resulted in partial defects in MAPK and Akt signaling that may account for the decreased papilloma growth in the TK(-/-) Tg.AC(+/-) mice. The papilloma-bearing mice were monitored for the occurrence of malignant skin tumors and other malignant tumor types for a period of 48 weeks. Loss of Ron receptor signaling significantly reduced the percent of papillomas that underwent malignant conversion as well as the number of mice developing other malignant tumor types. In conclusion, these studies demonstrate that Ron signaling augments papilloma growth and malignant conversion in vivo.     

What survival benefits do premenopausal patients with early breast cancer need to make endocrine therapy worthwhile?

BACKGROUND: Adjuvant endocrine therapies such as tamoxifen, goserelin, and oophorectomy improve survival for premenopausal women diagnosed with early-stage breast cancer. However, these treatments often result in menopausal symptoms, sexual dysfunction, permanent infertility, or the need to delay pregnancy. We aimed to quantify the survival gains that premenopausal patients with early-stage breast cancer require to justify the side-effects and inconvenience of adjuvant endocrine treatments. METHODS: Participants consisted of 102 women who had been diagnosed with early-stage (stage I-II) breast cancer 6-60 months previously, who were aged 40 years or younger at diagnosis, and who had been treated for a minimum of 3 months with endocrine therapy (67 with tamoxifen alone, seven with goserelin alone, and 28 with tamoxifen and goserelin or oophorectomy). 76 patients also received chemotherapy, and 75 received radiotherapy. Participants attended a face-to-face patient-preference interview, in which they were presented with four hypothetical clinical scenarios that were used to quantify the gains in survival rate and life expectancy that women judged necessary to make their endocrine therapy worthwhile. They also completed a questionnaire on standard psychological measures. FINDINGS: About half of participants thought that adjuvant endocrine therapy was worthwhile for an absolute gain in survival of 2% from a baseline of either 65% or 85%, and for a gain in life expectancy of 3 months from a baseline of 5 years and of 6 months for a baseline of 15 years. Women who had had more severe endocrine side-effects required larger gains to make endocrine therapy worthwhile (univariate p=0.02, multivariate p=0.04). INTERPRETATION: Modest gains in survival are sufficient to make adjuvant endocrine treatment worthwhile for premenopausal women with early-stage breast cancer. Knowing and incorporating what women think should enhance shared decision-making.     

Home health care nurses as a new channel for smoking cessation treatment: outcomes from project CARES (Community-nurse Assisted Research and Education on Smoking)

BACKGROUND: Clinical guidelines for smoking cessation may not be sufficient for helping some subgroups of smokers quit. Incorporating smoking cessation into home-based medical care can proactively reach high-risk smokers who may not have access to (or spontaneously seek) smoking cessation. METHOD: Home health care nurses (N = 98) were randomly assigned to deliver either Motivational Enhancement (ME; Motivational Interviewing + Carbon Monoxide Feedback) or Standard Care (AHCPR Guidelines for smoking cessation) to their patients. Seventy percent of patients were eligible and willing to participate (N = 273; 54% female, mean age = 57 years, 83% Caucasian, 41% < high school education). The study was conducted in Providence, RI, USA from 1998 to 2003. RESULTS: Biochemically verified continuous abstinence rates at the 12-month follow-up were 4.2% (SC) and 8.7% (ME) for intent to treat analyses, and 5.2% (SC) and 11.8% (ME) using all available cases (P > 0.05). ME reported more quit attempts and significantly greater reductions in the number of cigarettes smoked per day at all follow-ups through 12 months of post-treatment (all P values < 0.05). CONCLUSIONS: Use of an existing public health channel such as home health care to reach smokers who vary in their motivation to quit could have the potential for large public health impact.     

Mothers reframing physical activity: family oriented politicism, transgression and contested expertise in Australia

Mothers of young children are a population sub-group with one of the lowest levels of physical activity. This paper presents the findings from a qualitative study with 40 Australian mothers of children under school age. The research aimed to understand the tensions, dilemmas and trade-offs which women experience around physical activity within the contexts of their everyday lives as mothers of young children. The analysis shows that, in contrast to health promotion messages which frame physical activity as a positive and healthy behaviour, mothers of young children perceive activity as being both enhancing and threatening to their health and social relationships. Restrictive stereotypes of the 'good' mother make it difficult for many women to prioritise their own physical activity needs over their childrearing and domestic responsibilities. Nevertheless, women's involvement in physical activity is often underpinned by the maternal 'ethic of care' as something which can help them cope better with the challenges of being a mother and contribute to the wellbeing of the family. This article takes as its departure point the notion that the maternal 'ethic of care' creates previously unrecognised opportunities in relation to physical activity. For many mothers, physical activity can also be a way of challenging hegemonic discourses and extending what it means to be a good mother in contemporary society. Although largely overlooked by contemporary health promotion, it is women's family-oriented politicism and resistance to dominant meanings about motherhood, health and the 'ideal' body which create alternative possibilities for their participation and enjoyment of physical activity during early motherhood.     

Prehospital prediction of intensive care unit stay and mortality in blunt trauma patients

BACKGROUND: The success of a trauma system relies on transfer of patients from the field to the most appropriate hospital for definitive care. However, no consensus has been reached regarding the best criteria or triage tool for identifying patients injured seriously enough to warrant transfer to a trauma center. METHODS: Predictors of mortality and intensive care unit stay were identified and prediction models developed in a design data set. The performance of these models was evaluated in a test data set and compared with current trauma triage guidelines, derived from the American College of Surgeons model. RESULTS: The newly developed prediction models performed comparably with the current trauma triage guidelines. CONCLUSION: Although the performance of newly developed triage models was promising, their performance did not exceed that of the current trauma triage guidelines. In particular, the anatomic injury criteria appeared to be the key component of the current trauma triage guidelines.     

Does the presence of an upper extremity injury affect outcomes after major trauma?

BACKGROUND: There is a paucity of information about the impact of upper extremity (UE) injuries on patient outcomes, particularly after major trauma. METHODS: Data were obtained from a statewide trauma registry. Cases were defined as major trauma cases (Injury Severity Score > 15) with (UE group) and without (no-UE group) an associated upper extremity injury. Multivariate analysis was performed to identify independent predictors of outcome. RESULTS: Major trauma patients with UE injury were 1.5 times (p = 0.011) more likely than the no-UE group to have a length of stay greater than 7 days. After adjusting for age, mechanism of injury, and Injury Severity Score, UE injury was not an independent predictor of discharge destination. CONCLUSION: In major trauma patients, the presence of an upper extremity injury is a significant predictor of length of stay, indicating a greater complexity and cost of care associated with this group of major trauma patients.     

Predicting adolescent risk behaviors based on an ecological framework and assets

OBJECTIVES: To examine the relationship between an aggregate risk score (smoking, drinking, and number of sex partners) and measures of youth assets in a sample of 3439 youth aged 14-18 years. METHODS: Linear regression models for African American and white males and females predicted an aggregate risk score. RESULTS: After adjustments, the youth asset most predictive of risk was self/peer values regarding risk behaviors. Perceived school support was also predictive. CONCLUSIONS: Taking an ecological approach to the measurement of adolescent health behaviors contributes to our understanding of these risk behaviors.