Search

The prevalence of obesity is high resulting from chronic imbalances between energy intake and expenditure. On the expenditure side, regular exercise is associated with health benefits, including enhanced brain function. The benefits of exercise are not immediate and require persistence to be realized. Brain regions associated with health-related decisions, such as whether or not to exercise or controlling the impulse to engage in immediately rewarding activities (e.g., sedentary behavior), include reward processing and cognitive control regions. A 9 month aerobic exercise study will be conducted in 180 sedentary adults (n = 90 healthy weight [BMI = 18.5 to 26.0 kg/m(2)]; n = 90 obese [BMI = 29.0 to 41.0 kg/m(2)) to examine the brain processes underlying reward processing and impulse control that may affect adherence in a new exercise regimen. The primary aim is to use functional magnetic resonance imaging (fMRI) to examine reward processing and impulse control among participants that adhere (exercise >80% of sessions) and those that do not adhere to a nine-month exercise intervention with secondary analyses comparing sedentary obese and sedentary healthy weight participants. Our results will provide valuable information characterizing brain activation underlying reward processing and impulse control in sedentary obese and healthy weight individuals. In addition, our results may identify brain activation predictors of adherence and success in the exercise program along with measuring the effects of exercise and improved fitness on brain activation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The results of existing controlled clinical trials were synthesized to determine effects of aerobic exercise training on resting systolic (SBP) and diastolic blood pressure (DBP) among previously sedentary older adults, to quantify the magnitude of observed changes, and to examine the influence of the associated interventional variables on these changes. Studies were identified via a systematic computer database search, hand searching, and cross-referencing of previously located articles. All potentially eligible articles were carefully reviewed and examined with the established inclusion criteria. Twenty-three studies, representing a total of 1226 older subjects, were included in the final analysis. Robust statistically significant effects were found in terms of the pooled standardized effect size of - 0.33 ± 0.06 (p < 0.0001) in SBP and - 0.39 ± 0.09 (p < 0.0001) in DBP. When compared with the control group, net decreases in both SBP (- 5.39 ± 1.21 mmHg, p < 0.0001) and DBP (-3.68 ± 0.83 mmHg, p < 0.0001) were observed in older exercisers, representing a 3.9% and a 4.5% reduction, respectively. This meta-analytic study provides robust quantitative data to support the efficacy and effectiveness of controlled endurance exercise training in decreasing resting SBP and DBP among previously sedentary older adults.

This article collects and examines all references to doctors in rhetorical exercises used in ancient Greek and Roman schools in the Roman Empire. While doctors are sometimes portrayed positively as philanthropic, expert practitioners of their divinely sanctioned art, they are more often depicted as facing charges for poisoning their patients.

Weight management for individuals with intellectual and developmental disabilities (IDD) has received limited attention. Studies on weight management in this population have been conducted over short time frames, in small samples with inadequate statistical power, infrequently used a randomized design, and have not evaluated the use of emerging effective dietary strategies such as pre-packaged meals (PMs). Low energy/fat PMs may be useful in individuals with IDD as they simplify meal planning, limit undesirable food choices, teach appropriate portion sizes, are convenient and easy to prepare, and when combined with fruits and vegetables provide a high volume, low energy dense meal. A randomized effectiveness trial will be conducted in 150 overweight/obese adults with mild to moderate IDD, and their study partners to compare weight loss (6 months) and weight maintenance (12 months) between 2 weight management approaches: 1. A Stop Light Diet enhanced with reduced energy/fat PMs (eSLD); and 2. A recommended care reduced energy/fat meal plan diet (RC). The primary aim is to compare weight loss (0-6 months) and weight maintenance (7-18 months) between the eSLD and RC diets. Secondarily, changes in chronic disease risk factors between the eSLD and RC diets including blood pressure, glucose, insulin, LDL-cholesterol, and HDL-cholesterol will be compared during both weight loss and weight maintenance. Finally, potential mediators of weight loss including energy intake, physical activity, data recording, adherence to the diet, study partner self-efficacy and daily stress related to dietary change will be explored., (© 2013. Published by Elsevier Inc. All rights reserved.)

Fluid milk consumed in conjunction with resistance training (RT) provides additional protein and calcium, which may enhance the effect of RT on body composition. However, the literature on this topic is inconsistent with limited data in adolescents. Therefore, we examined the effects of a supervised RT program (6 mo, 3 d/ wk, 7 exercises, 40-85% 1-repetition maximum) with daily milk supplementation (24 oz/day, one 16-oz dose immediately post-RT) on weight, fat mass (FM), and fat-free mass (FFM) assessed via dual-energy X-ray absorptiometry (baseline, 3 mo, 6 mo) in a sample of middle-school students who were randomly assigned to 1 of 3 supplement groups: milk, isocaloric carbohydrate (100% fruit juice), or water (control). Thirty-nine boys and 69 girls (mean age = 13.6 yr, mean BMI percentile = 85th) completed the study: milk n = 36, juice n = 34, water n = 38. The results showed no significant differences between groups for change in body weight (milk = 3.4 ± 3.7 kg, juice = 4.2 ± 3.1 kg, water = 2.3 ±2.9 kg), FM (milk = 1.1 ±2.8 kg, juice = 1.6 ± 2.5 kg, water = 0.4 ±3.6 kg), or FFM (milk = 2.2 ± 1.9 kg, juice = 2.7 ± 1.9 kg, water = 1.7 ± 2.9 kg) over 6 mo. FFM accounted for a high proportion of the increased weight (milk = 62%, juice = 64%, water = 74%). These results from a sample of predominantly overweight adolescents do not support the hypothesis that RT with milk supplementation enhances changes in body composition compared with RT alone.

Objective: Compare weight loss and maintenance between a face-to-face (FTF) weight management clinic and a clinic delivered via virtual reality (VR)., Methods: Participants were randomized to 3 months of weight loss with a weekly clinic delivered via FTF or VR and then 6 months' weight maintenance delivered with VR. Data were collected at baseline and 3 and 6 months for weight and process variables. Twenty overweight and obese individuals (31.1 ± 3.6 years of age; body mass index, 32.8 ± 5.1; 85% females; 20% minorities) responded to advertisement and met inclusion criteria. Diets (1,200-1,800 kcal/d) used prepackaged meals, fruits and vegetables, and physical activity (300 min/wk)., Results: Weight loss was significantly greater for FTF at 10.8% compared with 7.6% for VR (P < .05). However, weight maintenance was significantly greater for VR at 14.0% compared with 9.5% for FTF (P < .05)., Conclusions and Implications: Virtual reality compares favorably with FTF for weight loss and may facilitate greater weight maintenance., (Copyright © 2013 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Background: Improving academic achievement and reducing the rates of obesity in elementary school students are both of considerable interest. Increased physical activity during academic instruction time during school offers a potential intervention to address both issues. A program titled "Physical Activity Across the Curriculum" (PAAC) was developed in which classroom teachers in 22 elementary schools were trained to deliver academic instruction using physical activity with a primary aim of preventing increased BMI. A secondary analysis of data assessed the impact of PAAC on academic achievement using the Weschler Individual Achievement Test-II and significant improvements were shown for reading, math and spelling in students who participated in PAAC. Based on the results from PAAC, an adequately powered trial will be conducted to assess differences in academic achievement between intervention and control schools called, "Academic Achievement and Physical Activity Across the Curriculum (A + PAAC).", Methods/design: Seventeen elementary schools were cluster randomized to A + PAAC or control for a 3-year trial. Classroom teachers were trained to deliver academic instruction through moderate-to-vigorous physical activity with a target of 100+ minutes of A + PAAC activities per week. The primary outcome measure is academic achievement measured by the Weschler Individual Achievement Test-III, which was administered at baseline (Fall 2011) and will be repeated in the spring of each year by assessors blinded to condition. Potential mediators of any association between A + PAAC and academic achievement will be examined on the same schedule and include changes in cognitive function, cardiovascular fitness, daily physical activity, BMI, and attention-to-task. An extensive process analysis will be conducted to document the fidelity of the intervention. School and student recruitment/randomization, teacher training, and baseline testing for A + PAAC have been completed. Nine schools were randomized to the intervention and 8 to control. A random sample of students in each school, stratified by gender and grade (A + PAAC = 370, Control = 317), was selected for outcome assessments from those who provided parental consent/child assent. Baseline data by intervention group are presented., Discussion: If successful, the A + PAAC approach could be easily and inexpensively scaled and disseminated across elementary schools to improve both educational quality and health., Funding Source: R01- DK85317., Trial Registration: US NIH Clinical Trials, http://NCT01699295.

Unlabelled: Exercise is recommended by public health agencies for weight management; however, the role of exercise is generally considered secondary to energy restriction. Few studies exist that have verified completion of exercise, measured the energy expenditure of exercise, and prescribed exercise with equivalent energy expenditure across individuals and genders., Objective: The objective of this study was to evaluate aerobic exercise, without energy restriction, on weight loss in sedentary overweight and obese men and women., Design and Methods: This investigation was a randomized, controlled, efficacy trial in 141 overweight and obese participants (body mass index, 31.0 ± 4.6 kg/m(2) ; age 22.6 ± 3.9 years). Participants were randomized (2:2:1 ratio) to exercise at either 400 kcal/session or 600 kcal/session or to a nonexercise control. Exercise was supervised, 5 days/week, for 10 months. All participants were instructed to maintain usual ad libitum diets. Because of the efficacy design, completion of ≥90% of exercise sessions was an a priori definition of per protocol, and these participants were included in the analysis., Results: Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9 kg (4.3%) and 5.2 ± 5.6 kg (5.7%), respectively, compared with weight gain for controls of 0.5 ± 3.5 kg (0.5%) (P < 0.05). Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant., Conclusions: Supervised exercise, with equivalent energy expenditure, results in clinically significant weight loss with no significant difference between men and women., (Copyright © 2012 The Obesity Society.)

Background: Alternative dosing is often used clinically to address common barriers with statin therapy, such as intolerance and cost. Previous findings have demonstrated significant and clinically similar reductions in low-density lipoprotein (LDL) cholesterol to daily dosing, when comparing similar total weekly doses., Objective: To determine whether rosuvastatin 80 mg once weekly produced comparable lipid and high-sensitivity C-reactive protein (hsCRP) changes to atorvastatin 10 mg daily, when measured at key points after last dose., Methods: This was a randomized, double-blind, parallel group, 8-week pilot study. Eligible subjects, 18 to 65 years of age, had documented dyslipidemia with LDL cholesterol >100 mg/dL and triglycerides <200 mg/dL. Participants were randomized to receive either rosuvastatin 80 mg once weekly (n = 10) or atorvastatin 10 mg daily (n = 10), for 8 weeks. Lipid panels and hsCRP were measured at baseline and 1-4 and 5-8 days after the last dose., Results: Participants in each arm experienced significant and comparable reductions from baseline in total cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio, non-high-density lipoprotein cholesterol, and overall LDL cholesterol (-29%). Changes in high-density lipoprotein cholesterol, triglycerides, and hsCRP were nonsignificant and similar between groups. Each regimen was well tolerated, with no major adverse events reported., Conclusion: Rosuvastatin 80 mg once weekly produced comparable lipid changes to atorvastatin 10 mg daily when measured at specific points after the last dose. Our findings support previous data demonstrating a significant reduction in LDL-C with once weekly statin dosing., (Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

With the large number of Veterans experiencing posttraumatic stress disorder (PTSD) and chronic pain, the purpose of this article is to review the prevalence of PTSD and chronic pain, the theoretical models that explain the maintenance of both conditions, and the challenges faced by providers and families who care for these patients. The Department of Veterans Affairs (VA)/Department of Defense (DOD) VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress with special attention to chronic pain is presented. Limited scientific evidence supports specific care and treatment of PTSD and chronic pain, and this challenges providers to investigate and research potential treatment options. Integrated care models designed for working with these patients are reviewed, including a focus on the techniques and strategies to address not only PTSD and chronic pain, but other conditions, including substance dependence and depression. A specific focus on headaches, back pain, and neuropathic pain follows, including treatment recommendations such as pharmacological, psychotherapeutic, and complementary approaches, given the high rates of these pain complaints for Veterans in PTSD clinical programs. Integrated care is presented as a viable solution and approach that challenges clinicians and researchers to develop innovative, scientifically based therapeutics and treatments to enhance the recovery and quality of life for Veterans with PTSD and chronic pain.

Policosanol is a poorly absorbed nutritional supplement used primarily for cholesterol management. Findings from previous trials evaluating the effects of policosanol are mixed with early data reporting positive lipid effects while more recent studies indicate negligible efficacy. We hypothesized that re-formulating policosanol would result in an improvement in major lipoproteins and possibly provide some explanation for previously conflicting trial data. Our primary objectives were to assess the efficacy and safety of modified-policosanol (MP) on the major lipoproteins among hyperlipidemic subjects receiving background statin therapy or as monotherapy. This 8-week clinical trial consisted of 3 arms. Subjects receiving chronic statin therapy (N = 36) were randomized in a double-blind design to MP 20 mg daily or placebo. In the third arm, subjects not receiving statin therapy (N = 18) were assigned open-label MP 20 mg daily. The utilization of MP when added to background statin therapy or as monotherapy resulted in no significant changes in major lipoproteins (all p > 0.05). The MP therapy was well tolerated with no major adverse events reported. Consistent with recent clinical trial data, MP demonstrated an excellent safety profile but produced no significant effects on major lipoproteins when used as monotherapy or when given with concomitant statin therapy.

One of the difficulties in examining organisational resilience in a community setting is the sheer complexity of the interrelationships essential to creating and sustaining that resilience. Very often, one is reduced to synthesising simpler hypothetical models to try to define and analyse the key aspects of resilience to volatility in the environment. This paper uses a university organisational setting as a real-life model of a community to explore the key arrangements essential for establishing resilience. Australia's worst recorded natural disaster, the devastating Victorian bushfires of February 2009, provides a context against which the resilience arrangements of an organisation, and by extrapolation a model community, can be examined.

Apolipoprotein E4 (apoE4) is a positively charged proinflammatory apolipoprotein bound to high-density lipoprotein (HDL) cholesterol and remnant lipoproteins. ApoE4 is associated with an increased risk of cardiovascular and cerebrovascular disease. Low-density lipoprotein (LDL) apheresis, a therapy for patients with familial hypercholesterolemia, removes apolipoprotein B and other positively charged plasma proteins but negatively charged proteins such as HDL cholesterol are generally spared. Despite their negative charge, LDL apheresis still removes 10% to 15% of HDL cholesterol, in particular, inflammatory HDL cholesterol. Patients with familial hypercholesterolemia have increased plasma levels of apoE4 and apoE4-bound HDL cholesterol. We tested the hypothesis that LDL apheresis would reduce the plasma levels of apoE4. We analyzed the plasma apoE4 levels using enzyme-linked immunosorbent assay immediately before and after LDL apheresis in 10 patients with familial hypercholesterolemia who had tested positive for the apoE4 isoform. After one treatment, the mean plasma apoE4 levels had been reduced by 39%, LDL cholesterol by 75%, triglycerides by 38%, and HDL cholesterol by 18%. The change in HDL cholesterol was significantly related to the apoE4 baseline values (r = -0.83, p = 0.001) and apoE4 levels after apheresis (r = 0.816, p = 0.004). In conclusion, LDL apheresis acutely reduced the plasma levels of apoE4. The mechanism of apoE4 reduction by LDL apheresis might be related to the selective reduction of a particular HDL cholesterol., (Copyright 2010. Published by Elsevier Inc.)

Background: Physical Activity Across the Curriculum (PAAC) was a three-year cluster randomized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children., Methods: Twenty-four elementary schools were cluster randomized to the Physical Activity Across the Curriculum intervention or served as control. All children in grades two and three were followed to grades four and five. Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers. Body Mass Index was the primary outcome, daily Physical activity and academic achievement were secondary outcomes., Results: The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9, respectively (NS). However, change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum. Schools with > or =75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had <75 min of Physical Activity Across the Curriculum (1.8+/-1.8 vs. 2.4+/-2.0, p=0.02). Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores., Conclusions: The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children. Additionally, 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index.

Objective: The purpose of this study was to compare the efficacy of two home-based weight loss interventions that differ only in the amount of outside support provided., Methods: This was a 12-week, randomized, controlled trial. One group received limited support (LWS, n = 35) via a single 10 min phone call each week while another group received no weekly support (NWS, n = 28). Both the LWS and NWS received pre-packaged meals (PM) and shakes. A third group served as control (CON, n = 30) and received no components of the intervention. Weight loss at 12 weeks was the primary outcome. Diet (PM, shake, and fruit/vegetable (F/V) intake) and physical activity (PA) were self-monitored, recorded daily and reported weekly. An exit survey was completed by participants in the intervention groups upon completion of the study., Results: Weight loss and percent weight loss in the LWS, NWS, and CON groups were 7.7 ± 4.4 kg (8.5 ± 4.2%), 5.9 ± 4.1 kg (6.0 ± 4.2%), and 0.3 ± 1.9 kg (0.4 ± 1.2%), respectively. The decrease in body weight and percent weight loss was significantly greater in the LWS and NWS groups when compared to the CON group and the percent weight loss was significantly greater in the LWS when compared to both the NWS and CON groups., Conclusion: A home-based weight loss program utilizing PM and shakes results in clinically significant percent weight loss and the addition of a brief weekly call promotes additional percent weight loss., (© 2009 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to determine the efficacy of rosuvastatin dosed once a week in patients with a previous statin adverse event. Rosuvastatin once a week was tolerated by 37 (74%) of the 50 study participants, with doses ranging from 2.5 mg to 20 mg a week (mean 10 +/- 4 mg). Patients tolerating the once-a-week regimen experienced a 17% reduction in total cholesterol, 23% reduction in low-density lipoprotein cholesterol, 12% reduction in triglycerides, and a 5% increase in high-density lipoprotein cholesterol (all p <0.001), during a mean follow-up of 4 months +/- 2. Although this alternative dosing regimen has not been proven to reduce cardiovascular events, it may provide a therapeutic option for patients who may otherwise go without the proven benefits of statin therapy. In conclusion, this dosing strategy was well tolerated in patients with a history of an adverse event to 1 or more statins and led to significant lipoprotein changes.

Background: Physical Activity Across the Curriculum (PAAC) is a 3-year elementary school-based intervention to determine if increased amounts of moderate intensity physical activity performed in the classroom will diminish gains in body mass index (BMI). It is a cluster-randomized, controlled trial, involving 4905 children (2505 intervention, 2400 control)., Methods: We collected both qualitative and quantitative process evaluation data from 24 schools (14 intervention and 10 control), which included tracking teacher training issues, challenges and barriers to effective implementation of PAAC lessons, initial and continual use of program specified activities, and potential competing factors, which might contaminate or lessen program effects., Results: Overall teacher attendance at training sessions showed exceptional reach. Teachers incorporated active lessons on most days, resulting in significantly greater student physical activity levels compared to controls (p < 0.0001). Enjoyment ratings for classroom-based lessons were also higher for intervention students. Competing factors, which might influence program results, were not carried out at intervention or control schools or were judged to be minimal., Conclusion: In the first year of the PAAC intervention, process evaluation results were instrumental in identifying successes and challenges faced by teachers when trying to modify existing academic lessons to incorporate physical activity.

We report the characterization of three UBA2 genes (UBA2a, -b, and -c; corresponding to At3g56860, At2g41060, and At3g15010) encoding Arabidopsis thaliana proteins with high homology to Vicia faba AKIP1 and other heterogeneous nuclear ribonucleoprotein (hnRNP)-type RNA-binding proteins. In vitro RNA binding assays revealed that the three UBA2 proteins interact efficiently with homoribopolymers. Biolistic transient expression of UBA2-GFPs demonstrated that the three UBA2 proteins localize to the nucleus. Expression analysis by RNA gel blot, RT-PCR, and promoter::GUS assays showed that UBA2 transcripts are present in all organs. UBA2 genes are subject to alternative splicing affecting only the 3'-untranslated regions (UTRs): six different splice variants were detected for UBA2a, and two each were found for UBA2b and UBA2c. RT-PCR and quantitative real-time RT-PCR analysis showed that the levels of UBA2 transcripts are regulated by wounding in a splice variant-specific manner: splice variants UBA2a.1 and UBA2c.1 increased following mechanical wounding. Wounding effects on gene expression are transduced by methyl jasmonate (MeJA)-dependent and oligogalacturonide (OGA)-dependent pathways. However, neither MeJA nor OGA treatment altered levels of any of the UBA2 transcripts, and other plant hormones implicated in wound responses, ethylene and abscisic acid (ABA), also had no effect on accumulation of UBA2 transcripts. Taken together, these results imply that the three UBA2 genes encode hnRNP-type nuclear RNA-binding proteins that function in a novel wound signal transduction pathway.

Objective: To examine weight loss maintenance among previous participants of a university-based behavioral weight management program and to compare behavioral strategies and perceived barriers between successful and unsuccessful maintainers., Method: Previous program participants (n=179) completed mailed surveys assessing current weight, weight control behaviors and perceived barriers to weight loss maintenance., Results: At 14.1+/-10.8 months following completion of treatment, survey respondents were on average 12.6+/-12.6 kg, or 11.3+/-10.7%, below baseline weight; 76.5% of respondents had successfully maintained weight, defined as maintaining a weight loss of at least 5% below baseline. Compared to unsuccessful maintainers, successful maintainers reported practicing four dietary and three physical activity weight control strategies more often and experiencing five barriers to healthy eating and exercise less often. After accounting for time since treatment and maximum weight loss while in treatment, the strongest correlates of successful weight loss maintenance were frequent exercise and perceived difficulty of weight management., Conclusions: Clinically meaningful weight loss maintenance was achieved by the majority of participants. Findings support the literature indicating that physical activity is one of the strongest predictors of successful weight loss maintenance. Findings also suggest that strategies to reduce the level of perceived effort required for long-term weight control may improve maintenance outcomes.

Background: Over the years schools have reduced physical education and recess time in favor of more academic instruction. Due to the drastic rise in obesity levels among children, some states have begun to mandate minimum amounts of physical activity (PA) that school children receive, causing schools to find alternative methods for increasing PA levels. Physical Activity Across the Curriculum (PAAC) is a 3-year randomized clinical trial incorporating moderate-intensity PA in elementary schools to reduce childhood obesity. This paper describes the rational, design, and methods of the PAAC intervention study., Methods: Twenty-two elementary schools were randomized to either a control or intervention condition. In schools randomized to the intervention condition (PAAC), regular classroom teachers were taught how to incorporate PA into standard academic lessons. Teachers were asked to accumulate 90-100 min/week of PAAC each week through out the 3-year study period. Schools randomized to the control group did not alter their teaching methods. Direct observation of PA levels in the classroom was collected weekly. Height and weight was measured twice a year to calculate BMI., Results: Two years of the intervention have been completed and only one school has left the study. The remaining 21 schools are participating in the final intervention year., Conclusions: The results from the PAAC intervention may provide schools with an alternative method to increase PA levels in children and reduce childhood obesity.

Background: Recent evidence suggests that a low carbohydrate (LC) diet may be equally or more effective for short-term weight loss than a traditional low fat (LF) diet; however, less is known about how they compare for weight maintenance. The purpose of this study was to compare body weight (BW) for participants in a clinical weight management program, consuming a LC or LF weight maintenance diet for 6 months following weight loss., Methods: Fifty-five (29 low carbohydrate diet; 26 low fat diet) overweight/obese middle-aged adults completed a 9 month weight management program that included instruction for behavior, physical activity (PA), and nutrition. For 3 months all participants consumed an identical liquid diet (2177 kJ/day) followed by 1 month of re-feeding with solid foods either low in carbohydrate or low in fat. For the remaining 5 months, participants were prescribed a meal plan low in dietary carbohydrate (~20%) or fat (~30%). BW and carbohydrate or fat grams were collected at each group meeting. Energy and macronutrient intake were assessed at baseline, 3, 6, and 9 months., Results: The LC group increased BW from 89.2 +/- 14.4 kg at 3 months to 89.3 +/- 16.1 kg at 9 months (P = 0.84). The LF group decreased BW from 86.3 +/- 12.0 kg at 3 months to 86.0 +/- 14.0 kg at 9 months (P = 0.96). BW was not different between groups during weight maintenance (P = 0.87). Fifty-five percent (16/29) and 50% (13/26) of participants for the LC and LF groups, respectively, continued to decrease their body weight during weight maintenance., Conclusion: Following a 3 month liquid diet, the LC and LF diet groups were equally effective for BW maintenance over 6 months; however, there was significant variation in weight change within each group.

Statins possess an excellent safety profile and are generally well tolerated when administered in the standard once-daily dosing regimen. A small percentage of patients however, discontinue therapy because of adverse events such as myalgias. The investigators describe 8 patients with previous intolerance to daily statin dosing and examine their responses to once-weekly rosuvastatin therapy. In conclusion, once-weekly rosuvastatin may be a feasible and effective option for patients previously intolerant to once-daily statin dosing.

The prominent use of fibric acid derivatives has lessened over the years because of unimpressive results in major clinical trials, safety concerns, and the emergence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Clofibrate was widely used in the 1970s, but after publication of results from two major trials demonstrating only modest reductions in the rate of coronary heart disease (CHD) and concerns regarding an increase in the frequency of gallstones and overall mortality, its use subsided dramatically. With the introduction of gemfibrozil in the 1980s came a renewed interest in the class, which was also supported by the published results of the Helsinki Heart Study; however, despite a significant reduction in CHD events and a sound safety profile, overall mortality was comparable to that with placebo. Again, in the 1990s, awareness of the fibrates was heightened with the availability of fenofibrate and the findings of another major trial using gemfibrozil, the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), which demonstrated impressive results in reducing cardiovascular events. To further strengthen the VA-HIT results, numerous post hoc analyses were performed on the data of major trials of fibrate therapy among patients with mixed dyslipidemia, with similar findings. Recently, however, data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were published, indicating mixed results. Nearly 40 years after the introduction of the fibrates, practitioners are still contemplating the role of these agents in the treatment of CHD.

As medical science progresses and the life spans of patients with serious illnesses increase, the process that leads to death is becoming more feared than death itself. This fear is particularly intense in technologically advanced cultures with access to advanced medical care. The lives of patients who previously would have died rapidly are now often extended. As a result, images of suffering, such as dying in isolation and experiencing great pain, often are at the forefront of concerns about those struggling with terminal illnesses. This article provides medical practitioners with an overview of the issues and symptoms common in terminal illness, to help them work most effectively with their mental health colleagues.

Objectives: The mode of contact and response levels of authors who had been asked to provide missing or incomplete data for a systematic review on diet and exercise interventions for weight loss was examined., Methods: We contacted authors by electronic mail, letter, or both. Survival analyses were performed with the Kaplan-Meier method to determine differences in the proportion of responders over time among the different modes of contact and to determine whether response rates differed between authors from the United States and those from other countries. Logistic regression was used to determine whether the number of items requested and publication date influenced the likelihood of response., Results: Two hundred forty-one (39.9 percent) studies had missing or incomplete data (e.g., sample size, age, caloric restriction, exercise amount, and so on). We were unable to locate ninety-five authors (39.4 percent). Of the remaining authors, forty-six authors (31.5 percent) responded to information requests. Time to respond differed by contact method (p < .05): e-mail (3 +/- 3 days), letter (27 +/- 30 days), and both (13 +/-12 days). Response rates from U.S. authors did not differ from those of other countries., Conclusions: Our study suggests poor success in the acquisition of essential information. Given considerable time and resources, weight loss studies require improved reporting standards to minimize the relatively unsuccessful attempt to contact authors for important and necessary information.

This meta-analysis of controlled clinical trials quantifies the effect of aerobic exercise on VO2max (aerobic fitness) among sedentary older adults and examines the associations of such magnitude with variables of intervention. Forty-one trials including 2102 older subjects (within-group mean age of 60 years and older) were identified by searches of databases, hand searching, and cross-referencing. Outcomes were homogeneous. The pooled standardized effect size by a fixed-effect model showed a higher moderate effect (mean +/- SEM) of 0.64+/-0.05; 95% confidence interval, 0.56-0.73; p<0.001, representing a net increase in VO2max (mean +/- SEM) of 3.78+/-0.28 mL.kg-1.min-1; 95% confidence interval, 3.24-4.33; or a 16.3% improvement, compared with control groups. Greater improvement in VO2max was associated with training length more than 20 weeks and training intensity of approximately 60% but less than 70% of VO2max. Endurance training improves aerobic fitness in older adults, thus providing protective benefits for cardiovascular aging and quality of later life.

Purpose of Review: The ability of high-density lipoprotein cholesterol to reverse atherosclerosis and reduce cardiovascular disease has been shown in several randomized controlled trials. One mechanism by which high-density lipoprotein cholesterol protects the vascular system includes hemorheology, the study of blood flow., Recent Findings: Blood viscosity, or the resistance of flow, can be altered by red blood cell aggregation, red blood cell deformability, and plasma viscosity. Elevated high-density lipoprotein cholesterol levels may improve all of these rheological mediators. An infusion of recombinant high-density lipoprotein cholesterol can immediately release nitric oxide, a potent vasodilator and responder to changes in rheology, into the arteries by activation of endothelial nitric oxide synthase. The stimulation of nitric oxide release by high-density lipoprotein cholesterol may also alter blood rheology., Summary: In this article, we will review hemorheology, particularly blood viscosity along with other hemorheological factors, and examine their association with high-density lipoprotein cholesterol.

Objective: To review the effects of lipid-lowering therapy on small-dense low-density lipoprotein cholesterol (sdLDL-C)., Data Sources: Literature was obtained from MEDLINE (1989-September 2004) and references of selected articles. Key search terms included small-dense LDL-C and lipid-lowering drug therapy., Data Synthesis: Statins, fibrates, and niacin have demonstrated favorable effects on sdLDL-C, especially among patients with mixed dyslipidemia or hypertriglyceridemia. These effects include a reduction of sdLDL-C and/or a shift to the larger, less atherogenic LDL-C., Conclusions: Data suggest that statins, fibrates, and niacin are effective at reducing concentrations of sdLDL-C and possibly normalizing LDL-C subclasses.

Background: To adequately assess individual studies and synthesize quantitative research on weight loss studies, transparent reporting of data is required. The authors examined the reporting quality of randomized trials in the weight loss literature, focusing exclusively on subject characteristics as they relate to enrollment, allocation, and follow-up., Methods: An extensive literature review, which included a computerized search of the MEDLINE database, manual searches of bibliographic references, and cross-referencing of 92 review articles was conducted. A checklist, based on CONSORT recommendations, was used to collect information on whether or not authors reported age, gender, co-morbid disease, medication use, race/ethnicity, and postmenopausal status. Also tracked was whether or not initial and final sample size was reported and stratified by gender., Results: Of 604 possible articles, 231 articles met eligibility criteria. Important subject characteristics were not reported as the following breakdown indicates: age (11%), gender (4%), race/ethnicity (86%), co-morbid disease states (34%), and medication use (92%). Additionally, 21% of articles failed to report initial sample size by gender while 69% neglected to report final sample size by gender., Conclusion: Inadequate reporting can create difficulties with interpretation and can lead to biased results receiving false credibility. The quality of reporting for weight loss studies needs considerable improvement.

Background: An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence., Objective: To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations., Method: Literature was obtained from MEDLINE (1966 - June 2005) and references from selected articles., Results: A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising., Conclusion: Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy.

Few studies have been designed to study the hemodynamic effects of low-density lipoprotein apheresis, especially on whole blood viscosity. Six patients with cardiovascular disease and hypercholesterolemia underwent a single low-density lipoprotein apheresis, resulting in significant reductions in whole blood viscosity at all shear rates.

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) has been shown to have IGF independent actions that appear to be mediated by specific IGFBP-3 binding proteins located on cell membranes. We show here using Western ligand blotting, a number of mammary membrane proteins that bind 125I-labeled rhIGFBP-3. Immunoprecipitation studies demonstrated that the >70 kDa protein was identified from bovine mammary microsomes as bovine lactoferrin (bLf). In addition to being a secretory protein, Lf is tightly associated with cellular membranes. Labeled rhIGFBP-3 was shown to bind to commercially purchased and processed apo- or holo-human or bLf, but not bovine transferrin (bTf). Binding of [125I]rhIGFBP-3 to other positively charged proteins was not detected nor was binding to rhIGFBP-5 or other mammary-secreted IGFBPs observed. Reciprocal specific binding of [125I]bLf to rhIGFBP-3 was shown, but [125I]bTf did not show binding to rhIGFBP-3. While [125I]rhIGF-II does not bind to bLf, unlabeled rhIGF-II was shown to compete with [125I]bLf for rhIGFBP-3 binding. More detailed analysis by dot blot showed that Lf competes (ED(50)=3 microg/ml) or displaces (ED(50)=1mg/ml) bound [125I]rhIGF-II from dot blotted rhIGFBP-3. In vitro studies with a bovine primary mammary epithelial cell culture showed that all-trans-retinoic acid stimulates the appearance of bovine IGFBP-3 and bLf in the conditioned media and that [125I]rhIGFBP-3 could be utilized to detect conditioned media bLf. These findings reveal a novel role for bLf, binding to IGFBP-3 and perhaps disassociating IGFBP-3:IGF when in high concentration.

Studies reveal important prognostic relationships between C-reactive protein (CRP) and atherosclerotic complications. A prospective trial of familial hypercholesterolemic patients treated with Heparin-induced Extra-corporeal Low-Density Lipoprotein Precipitation (HELP, B. Braun Melsungen) therapy was undertaken to evaluate the short- and long-term effects on CRP. Four patients received LDL apheresis therapy on an alternate week basis for 6 months. Pre- and post-treatment serum high sensitivity (hs) CRP levels (IMx(R), Abbott Laboratories), LDL-C, triglycerides, and fibrinogen were measured. Pre- and post-treatment mean serum levels of LDL-C were 281+/-76 and 98+/-34 mg/dl; triglycerides 191+/-64 and 123+/-50 mg/dl; fibrinogen 332+/-46 and 117+/-31 mg/dl, respectively. Before and after apheresis mean serum levels of hsCRP were 8.99+/-7.88 and 3.15+/-3.16 mg/ml, respectively, representing a 65% decrease. After 6 months of therapy, pre-treatment hsCRP showed an overall mean level decrease of 49%. Preliminary results indicate that LDL apheresis results in a rapid and long-term decrease of serum hsCRP levels.

This review concerns the clinical impact of low-density lipoprotein (LDL) apheresis for patients with refractory hypercholesterolemia. We examine and provide examples of investigations that have demonstrated the clinical benefits of LDL apheresis. In addition to benefits derived from the stabilization or regression of arterial lesions, we highlight other possible mechanisms related to clinical improvement. We also discuss the potential advantages of lipid apheresis for the treatment of patient populations other than those characterized by severe hypercholesterolemia and premature coronary heart disease.

Objective: This study was conducted to compare the collection of endocervical specimens by endocervical brush, curette, and a combined curette and brush technique., Methods: Women underwent colposcopy with endocervical curettage using one of 3 collection methods., Results: The endocervical brush produced equivalent amounts of tissue and endocervical cells compared to the curette alone or combined techniques. More squamous and glandular atypia and SIL/AIS were found when a brush was used, but a statistically significant difference was not noted. The brush alone produced a significantly greater percentage of samples that were insufficient for diagnosis and more specimens without stromal components. The brush with the curette as a combined technique provided no improvement in amounts of tissue, endocervical cells/clusters, or amount of stroma retrieved., Conclusion: Each technique has advantages and disadvantages in terms of what types of components are collected and what diagnosis may be determined from the sample taken.

The coronavirus mouse hepatitis virus (MHV) translates its replicase gene (gene 1) into two co-amino-terminal polyproteins, polyprotein 1a and polyprotein 1ab. The gene 1 polyproteins are processed by viral proteinases to yield at least 15 mature products, including a putative RNA helicase from polyprotein 1ab that is presumed to be involved in viral RNA synthesis. Antibodies directed against polypeptides encoded by open reading frame 1b were used to characterize the expression and processing of the MHV helicase and to define the relationship of helicase to the viral nucleocapsid protein (N) and to sites of viral RNA synthesis in MHV-infected cells. The antihelicase antibodies detected a 67-kDa protein in MHV-infected cells that was translated and processed throughout the virus life cycle. Processing of the 67-kDa helicase from polyprotein 1ab was abolished by E64d, a known inhibitor of the MHV 3C-like proteinase. When infected cells were probed for helicase by immunofluorescence laser confocal microscopy, the protein was detected in patterns that varied from punctate perinuclear complexes to large structures that occupied much of the cell cytoplasm. Dual-labeling studies of infected cells for helicase and bromo-UTP-labeled RNA demonstrated that the vast majority of helicase-containing complexes were active in viral RNA synthesis. Dual-labeling studies for helicase and the MHV N protein showed that the two proteins almost completely colocalized, indicating that N was associated with the helicase-containing complexes. This study demonstrates that the putative RNA helicase is closely associated with MHV RNA synthesis and suggests that complexes containing helicase, N, and new viral RNA are the viral replication complexes.

Objective: We conducted this study to determine if a smoking status stamp would prompt physicians to increase the number of times they ask, advise, assist, and arrange follow-up for African-American patients about smoking-related issues., Design: An intervention study with a posttest assessment (after the physician visit) conducted over four 1-month blocks. The control period was the first 2 weeks of each month, while the following 2 weeks served as the intervention period., Setting: An adult walk-in clinic in a large inner-city hospital., Participants: We consecutively enrolled into the study 2,595 African-American patients (1,229 intervention and 1, 366 control subjects) seen by a housestaff physician., Interventions: A smoking status stamp placed on clinic charts during the intervention period., Main Results: Forty-five housestaff rotated through the clinic in 1-month blocks. In univariate analyses, patients were significantly more likely to be asked by their physicians if they smoke cigarettes during the intervention compared with the control period, 78.4% versus 45.6% (odds ratio [OR] 4.28; 95% confidence interval [CI] 3.58, 5.10). Patients were also more likely to be told by their physician to quit, 39.9% versus 26.9% (OR 1.81; 95% CI 1.36, 2.40), and have follow-up arranged, 12.3% versus 6.2% (OR 2.16; 95% CI 1.30, 3.38)., Conclusions: The stamp had a significant effect on increasing rates of asking about cigarette smoking, telling patients to quit, and arranging follow-up for smoking cessation. However, the stamp did not improve the low rate at which physicians offered patients specific advice on how to quit or in setting a quit date.

Insulin-like growth factor system components are synthesized and secreted by mammary epithelial cells and multiple IGF binding proteins (IGFBP) are found in milk of various species. This study was conducted to identify the IGFBP in bovine milk, to compare them with those found in blood, and to identify the cell(s) responsible for mammary IGFBP synthesis. Bovine blood, milk, and cell culture-conditioned media were analyzed and characterized with Western ligand blot procedures for specific IGFBP. Electrophoresis and [125I]IGF-II ligand blot analyses of the samples indicated that, unlike serum and mammary primary cell culture-conditioned media, milk required removal of casein in order to accurately disclose all IGFBP. Immunoprecipitation studies identified IGFBP-2, -3, -4, and -5 in blood, milk, and primary cell culture conditioned media. The IGFBP were present at higher concentrations in serum than in milk, and milk concentrations were greater than that shown in conditioned media from primary cultures of bovine mammary cells. Northern analysis detected IGFBP-3 messenger RNA in extracts from fresh tissue and cells in culture, and in situ hybridization studies with fresh tissue utilizing probes for IGFBP-3 and alphaS1-casein showed that the mRNA for IGFBP-3 is predominant in the secretory epithelial cells, when compared to other tissue cell types.

Newborn rat pups were artificially reared by the pup in cup (PIC) method to determine whether dietary long arginine3 IGF-I (long R3 IGF-I), an IGF-I analog with high receptor affinity and low IGF binding protein (IGFBP) affinity, had efficacy on intestinal growth. IGF effects are mediated by IGFBP and receptor interactions, hence dietary-induced changes in intestinal IGF-II receptor patterns and IGFBP-3 message levels were investigated. Intestinal micrographs of pups fed rat milk replacer (RMR) for 3 d showed flattened villi with low cell counts and appeared similar to newborn intestines. Mother-fed (MF) controls and long R3 IGF-I-fed pups showed increased villi height and cell counts when compared with RMR pups, with long R3 IGF-I fed pups showing the greatest increase. At birth IGF-II-specific binding was not uniform in the intestine; specific binding was higher in the proximal intestinal section than in the distal intestinal section. However, after 3 d of MF treatment, specific binding had reversed and the distal section showed higher IGF-II-specific binding. Three days of RMR feeding did not change IGF-II-specific binding from that of the newborn pup. An IGFBP-3 message was identified in intestinal epithelium by in situ hybridization. Northern analysis of IGFBP-3 message showed a decline over time, but the change was not influenced by dietary treatments. In summary, milk-borne growth factors have the potential to affect intestinal growth within 3 d of treatment.

The human astroviruses (HAst) are increasingly recognized as an important cause of gastroenteritis. These viruses contain a 6.8-kb positive-sense, single-stranded RNA molecule that is infectious when transfected into permissive cells. The HAst gene 1 is composed of two open reading frames (ORFs 1a and 1b) connected by a ribosomal frameshift. Gene 1 is predicted to encode two nonstructural polyproteins (pp 1a and pp 1ab), and analysis of the HAst gene 1 sequence has resulted in predictions of a serine proteinase within the ORF1a polyprotein. However, none of the gene 1 proteins have been identified. To examine the expression and processing of the HAst2 gene 1 polyprotein, we have translated pp 1a and pp 1ab in vitro. These ongoing studies will provide the foundation for correlating gene 1 expression in vitro with proteins expressed in virus-infected cells.

The 3C-like proteinase of mouse hepatitis virus (MHV-3CLpro) is predicted to cleave at least 10 sites in the gene 1 polyprotein, resulting in processing of proteinase, polymerase and helicase proteins from the polyprotein. We have used E. coli expressed recombinant 3CLpro (r3CLpro) to define cleavage sites in carboxy-terminal region of the ORF 1a polyprotein. Polypeptides containing one or more putative 3CLpro cleavage site were translated in vitro from subcloned regions of gene 1, and the polypeptides were incubated with r3CLpro. Analysis of the cleavage products confirmed several putative cleavage sites, as well as identifying cleavage sites not previously predicted by analysis of the MHV sequence. Antibodies directed against a portion of the ORF 1a polyprotein were used to probe virus infected cells, and detected proteins that correspond to the cleavage sites used by 3CLpro in vitro. These results suggest that MHV 3CLpro cleaves at least 7 sites in the ORF 1a polyprotein, and that the specificity of 3CLpro for cleavage site dipeptides may be broader than previously predicted.

The hypothesis that dietary L-arginine (L-Arg) supplementation would increase growth hormone (GH) secretion and antibody production in preruminant calves was tested. Sixteen newborn calves were randomly assigned to either Arg+ or Arg- treatment groups. Both groups were fed a single dose of Colostrx within 6 h after birth followed by milk replacer twice daily until weaning. Beginning with the Colostrx feeding, calves in the Arg+ group were supplemented with L-arginine at 500 mg kg x BW(-1) x d(-1), and the Arg- group received equivalent, but unsupplemented, diets. All calves were immunized against keyhole limpet hemocyanin (KLH) on d 4 and received a booster vaccination on d 14. The Arg+ treatment increased (P < .05) plasma L-Arg and urea concentrations an average of 2.8-fold and 26%, respectively, during the 4-wk supplementation period. Average daily gain (ADG) of Arg+ calves was increased (P < .10) during wk 1, 3, and 5 of life. The Arg+ treatment depressed (P < .05) total and KLH-specific IgG concentrations in plasma and caused a decrease (P < .01) in circulating leukocyte numbers. Differential counts revealed that the decrease in circulating leukocyte numbers was due to decreases in absolute numbers of lymphocytes, monocytes, and neutrophils. The Arg+ diet did not affect mean plasma GH concentrations during the first 3 wk of life, but GH mean concentrations were decreased (P < .01) during wk 4 due to depressed (P < .10) pulse amplitudes. The decrease in GH mean concentrations during wk 4 was paralleled by lower (P < .10) plasma IGF binding protein-3 concentrations. These data show that supplementary L-Arg does not increase plasma GH concentrations, but it increases ADG, depresses KLH antibody production, and alters circulating leukocyte populations in preruminant calves.

In this study, we investigated the relationship between reovirus-induced apoptosis and viral growth. Madin-Darby canine kidney (MDCK) epithelial cells infected with prototype reovirus strains type 1 Lang (T1L) or type 3 Dearing (T3D) were found to undergo apoptosis, and T3D induced apoptosis of MDCK cells to a substantially greater extent than T1L. By using T1L x T3D reassortant viruses, we found that differences in the capacities of these strains to induce apoptosis are determined by the viral S1 and M2 gene segments. These genes encode viral outer-capsid proteins that play important roles in viral entry into cells. T1L grew significantly better in MDCK cells than T3D, and these differences in growth segregated with the viral L1 and M1 gene segments. The L1 and M1 genes encode viral core proteins involved in viral RNA synthesis. Bcl-2 overexpression in MDCK cells inhibited reovirus-induced apoptosis but did not substantially affect reovirus growth. These findings indicate that differences in the capacities of reovirus strains to induce apoptosis and grow in MDCK cells are determined by different viral genes and that premature cell death by apoptosis does not limit reovirus growth in MDCK cells.

A subcloned mouse mammary epithelial cell line (COMMA-D/MME) was cultured on Engelbreth-Holm-Swarm (EHS) tumor cell matrix with lactogenic hormones (insulin, cortisol, prolactin) to stimulate differentiation and challenged with growth factors to interpret the relationship between the signals for growth and differentiation. After 21 days of pretreatment to promote differentiation, cells were capable of growth, but were always less responsive than cells that did not receive lactogenic pretreatment. Although the cells failed to express beta-casein mRNA, droplets of neutral lipids were present in the cell cytoplasm regardless of treatment. Lactogenic hormones induced the appearance of larger droplets that occurred in intracytoplasmic lumens and lipid synthesis rates were initially increased. However, the glycerol incorporation pattern of these lipids only reached 53% of the changes expected for lactating tissue. Furthermore, because secretion of the lipid was inhibited, the accumulation eventually inhibited synthetic capacity. The cellular expression of acetyl Co-A carboxylase message was increased by growth, but not by lactogenic treatments. It is concluded that the COMMA-D/MME are capable of partial and transient differentiation to synthesize milk lipids, but are inhibited by the accumulation of material due to inability to secrete.

Ross River and Sindbis viruses were isolated from Aedes camptorhynchus adults reared from immatures collected from a salt marsh in coastal Victoria, indicating the existence of field vertical transmission. These first isolations of an arbovirus from adult mosquitoes reared from field-collected immatures in Australia indicates one mechanism for arbovirus maintenance in temperate regions.

Urokinase plasminogen activator (u-PA) receptor (u-PAR) is a glycosyl-phosphatidylinositol-anchored membrane protein that promotes pericellular proteolysis and cellular migration. This investigation demonstrates that u-PAR is a substrate for the proteolytically active form of streptococcal pyrogenic exotoxin B (SPE B), a potent virulence factor secreted by Streptococcus pyogenes. Treatment of U937 monocyte-like cells with SPE B decreased specific 125I-labeled single-chain u-PA binding by up to 85%. Cysteine proteinase inhibitors neutralized SPE B without affecting the activity of phosphatidylinositol-specific phospholipase C. Due to decreased u-PA binding, SPE B-treated U937 cells expressed decreased activity against a u-PA-specific fluorogenic substrate and plasminogen. SPE B released single-chain u-PA that was noncovalently bound to U937 cells or cross-linked to cellular receptors with bis(sulfosuccinimidyl) suberate. The mass of the released u-PA-receptor complex was 100 kDa. Western blot analysis confirmed that the u-PA receptor that was cleaved by SPE B is u-PAR. After deglycosylation, the mass of SPE B-released u-PAR was 35 kDa, slightly smaller than the phosphatidylinositol-specific phospholipase C-derived form of this receptor. SPE B-released u-PAR retained the ability to bind u-PA, as determined by u-PA affinity chromatography. We conclude that SPE B may inhibit u-PA binding to monocytic cells by at least two mechanisms: (i) by decreasing the level of functional cell surface u-PAR and (ii) by releasing a soluble form of u-PAR that competes with the cellular receptor for ligand.

The goal of this study was to relate insulin-like growth factor (IGF) binding with IGF-stimulated growth in a murine mammary epithelial (COMMA-D/MME) cell line. Affinity crosslinking with [125I]IGF-I showed major bands at 224,000 and 148,000 Mr that were ablated by the inclusion of IGF-I or -II at 130 nM. Scatchard-transformed [125I]IGF-I binding data was best fit by a two-site model, with 24,000 sites possessing a Kd of 0.33 nM and 1,000 sites possessing a Kd of 8.09 nM per cell. Competition analysis showed ED50 values for IGF-I, -II, and insulin to be 0.90 +/- 0.03, 7.15 +/- 4.27, and 335 +/- 104 nM, respectively. Affinity crosslinking of [125I]IGF-II showed three major bands of 230,000, 148,000, and 61,000 to 58,000 Mr. Unlabeled IGF-II ablated all bands, while IGF-I and insulin ablated only the 148,000 Mr band. Competition analysis showed ED50 values for unlabeled IGF-I and -II to be 0.10 +/- 0.01 and 5.31 +/- 2.04 nM, respectively. In spite of the receptor affinity differences, no significant difference was noted in IGF-I and -II in capacity to stimulate cell growth. These data indicate that COMMA-D/MME cells express IGF receptors and that both IGFs are mitogenic.

A study of the anthropometric status of under-5-year-olds was conducted in the Nqutu district of KwaZulu by means of a representative community-based sample and concurrent samples from primary health care clinics, preschools and primary schools. The first objective of this exercise was to determine the extent of acute nutritional stress in the district as an indication of the appropriateness of food relief efforts in the region. The absence of wasting and the high prevalence of stunting (37.5%) in the community-based sample suggested that the main problem is chronic socio-economic underdevelopment, rather than a severe or immediate lack of food. The fact that fewer than 20% of households are in any way reliant on domestic production for their maize requirements explains why the recent drought has not had a greater impact on the nutritional status of this vulnerable group. This study confirms that the more recent emphasis of the National Nutrition and Social Development Programme on social development is appropriate. An equally important objective of this study was to evaluate the usefulness of clinics, preschools and schools as sites for the collection of anthropometric data and the development of nutritional programmes. This preliminary attempt to develop the methodology for district-based nutrition surveillance suggested that all these sites have limitations both in respect of data collection and community access. The implications of using these sites and the developments needed to improve their usefulness in a future nutrition surveillance system are discussed.

The virulence of a yellow fever (YF) virus (P-16065) isolated from a fatal case of vaccine-associated viral encephalitis was investigated. P-16065 appeared identical to its parent vaccine virus (17D-204 USA, lot 6145) when examined with monoclonal antibodies except that YF wild type-specific MAb S24 recognized P-16065 but not 17D-204 USA 6145. Thus, a mutation of at least one epitope on the envelope (E) protein had occurred. Unlike 17D-204 USA 6145 and other 17D vaccine viruses, P-16065 was neuroinvasive and virulent for mice after intranasal inoculation, and neurovirulent for monkeys after intracerebral inoculation. The E protein of P-16065 differed from 17D-204 USA by two amino acids at positions 155 and 303. Changes at amino acid position 155 are found in other YF vaccine viruses that are not neurovirulent, and it is therefore postulated that the change at position 303 is involved in the alteration of the phenotype of P-16065 and may be important for virulence of YF virus.