Comparison of the Interactions of Transferrin Receptor and Transferrin Receptor 2 with Transferrin and the Hereditary Hemochromatosis Protein HFE

The transferrin receptor (TfR) interacts with two proteins important for iron metabolism, transferrin (Tf) and HFE, the protein mutated in hereditary hemochromatosis. A second receptor for Tf, TfR2, was recently identified and found to be functional for iron uptake in transfected cells (Kawabata, H., Germain, R. S., Vuong, P. T., Nakamaki, T., Said, J. W., and Koeffler, H. P. (2000) J. Biol. Chem. 275, 16618-16625). TfR2 has a pattern of expression and regulation that is distinct from TfR, and mutations in TfR2 have been recognized as the cause of a non-HFE linked form of hemochromatosis (Camaschella, C., Roetto, A., Cali, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., and Gasparini, P. (2000) Nat. Genet. 25, 14-15). To investigate the relationship between TfR, TfR2, Tf, and HFE, we performed a series of binding experiments using soluble forms of these proteins. We find no detectable binding between TfR2 and HFE by co-immunoprecipitation or using a surface plasmon resonance-based assay. The affinity of TfR2 for iron-loaded Tf was determined to be 27 nM, 25-fold lower than the affinity of TfR for Tf. These results imply that HFE regulates Tf-mediated iron uptake only from the classical TfR and that TfR2 does not compete for HFE binding in cells expressing both forms of TfR

Methods and Baseline Characteristics of Two Group-Randomized Trials With Multiracial and Multiethnic Working-class Samples

Introduction: Few papers address the methodological challenges in recruiting participants for studies of cancer prevention interventions designed for multiracial and multiethnic working-class populations. This paper reports the results of the sample selection and survey methods for two group-randomized intervention studies. Methods: The two group-randomized intervention studies, Healthy Directions–Small Business (HD–SB) and Healthy Directions–Health Centers (HD–HC), included a worksite-based study in 26 small manufacturing businesses and a study in 10 outpatient health centers. We used selection and recruitment methods to obtain a multiracial and multiethnic working-class study sample. In 2000 and 2001, we assessed baseline measures of sociodemographic characteristics and behavioral outcomes by self-report. We then computed intraclass correlation coefficients (ICCs). Results: Of the 1740 participants in the HD–SB study, 68% were non-Hispanic whites, and 76% had working-class occupations. In the HD–HC study, 59% of 2219 participants were non-Hispanic whites. Among those who worked, 51% had working-class occupations. Large percentages of both samples reported not meeting recommended guidelines for the target behaviors. For example, 86% of members of both samples consumed fewer than the recommended five servings of fruits and vegetables per day. The ICCs for the four target behaviors in HD–SB were between 0.006 and 0.02. In the HD–HC study, the ICCs ranged from 0.0004 to 0.003. Conclusion: The two studies were successful in recruiting multiracial and multiethnic working-class participants. Researchers will find the estimates of the primary outcomes and their ICCs useful for planning future studies

Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011.

BackgroundSince the introduction of the Haemophilus influenzae serotype b vaccine, H influenzae epidemiology has shifted. In the United States, the largest burden of disease is now in adults aged ≥65 years. However, few data exist on risk factors for disease severity and outcome in this age group.MethodsA retrospective case-series review of invasive H influenzae infections in patients aged ≥65 years was conducted for hospitalized cases reported to Active Bacterial Core surveillance in 2011.ResultsThere were 299 hospitalized cases included in the analysis. The majority of cases were caused by nontypeable H influenzae, and the overall case fatality ratio (CFR) was 19.5%. Three or more underlying conditions were present in 63% of cases; 94% of cases had at least 1. Patients with chronic heart conditions (congestive heart failure, coronary artery disease, and/or atrial fibrillation) (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.65-6.46), patients from private residences (OR, 8.75; 95% CI, 2.13-35.95), and patients who were not resuscitate status (OR, 2.72; 95% CI, 1.31-5.66) were more likely to be admitted to the intensive care unit (ICU). Intensive care unit admission (OR, 3.75; 95% CI, 1.71-8.22) and do not resuscitate status (OR, 12.94; 95% CI, 4.84-34.55) were significantly associated with death.ConclusionsWithin this age group, burden of disease and CFR both increased significantly as age increased. Using ICU admission as a proxy for disease severity, our findings suggest several conditions increased risk of disease severity and patients with severe disease were more likely to die. Further research is needed to determine the most effective approach to prevent H influenzae disease and mortality in older adults

Differences in Inflammatory Markers between Nulliparous Women Admitted to Hospitals in Preactive vs Active Labor

Objective To determine whether labor-associated inflammatory markers differ between low-risk, nulliparous women in preactive vs active labor at hospital admission and over time. Study Design Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (n = 118) sampled from 2 large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil, and monocyte counts; and serum inflammatory cytokines (interleukin -1β, interleukin-6, tumor necrosis factor-α, interleukin-10) and chemokines (interleukin-8). Biomarker concentrations and their patterns of change over time were compared between preactive (n = 63) and active (n = 55) labor admission groups using Mann-Whitney U tests. Results Concentrations of interleukin-6 and interleukin-10 in the active labor admission group were significantly higher than concentrations in the preactive labor admission group at all 3 time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and interleukin-10 between admission and 2 hours later was faster in the active group (P \u3c .001 and P = .003, respectively). Conclusion Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared with those admitted in preactive labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission

Level of dietary protein intake affects glucose turnover in endurance-trained men

<p>Abstract</p> <p>Background</p> <p>To examine the effects of higher-protein diets on endogenous glucose metabolism in healthy, physically active adults, glucose turnover was assessed in five endurance-trained men (age 21.3 ± 0.3 y, VO_2peak70.6 ± 0.1 mL kg^-1min^-1) who consumed dietary protein intakes spanning the current dietary reference intakes.</p> <p>Findings</p> <p>Using a randomized, crossover design, volunteers consumed 4 week eucaloric diets providing either a low (0.8 g kg^-1d^-1; LP), moderate (1.8 g kg^-1d^-1; MP), or high (3.6 g kg^-1d^-1; HP) level of dietary protein. Glucose turnover (Ra, glucose rate of appearance; and Rd glucose rate of disappearance) was assessed under fasted, resting conditions using primed, constant infusions of [6,6-²H₂] glucose. Glucose Ra and Rd (mg kg^-1min^-1) were higher for MP (2.8 ± 0.1 and 2.7 ± 0.1) compared to HP (2.4 ± 0.1 and 2.3 ± 0.2, <it>P </it>< 0.05) and LP (2.3 ± 0.1 and 2.2 ± 0.1, <it>P </it>< 0.01) diets. Glucose levels (mmol/L) were not different (<it>P </it>> 0.05) between LP (4.6 ± 0.1), MP (4.8 ± 0.1), and HP (4.7 ± 0.1) diets.</p> <p>Conclusions</p> <p>Level of protein consumption influenced resting glucose turnover in endurance athletes in a state of energy balance with a higher rate of turnover noted for a protein intake of 1.8 g kg^-1d^-1. Findings suggest that consumption of protein in excess of the recommended dietary allowance but within the current acceptable macronutrient distribution range may contribute to the regulation of blood glucose when carbohydrate intake is reduced by serving as a gluconeogenic substrate in endurance-trained men.</p

Invasive Group A Streptococcal Infection in Older Adults in Long-term Care Facilities and the Community, United States, 1998–20031

Invasive infection develops almost 6 times as frequently in the elderly in long-term care facilities