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Maribeth H. Johnson

Bio: Maribeth H. Johnson is an academic researcher from Georgia Regents University. The author has contributed to research in topics: Stroke & Stromal cell. The author has an hindex of 45, co-authored 125 publications receiving 5189 citations. Previous affiliations of Maribeth H. Johnson include Charlie Norwood VA Medical Center.


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Journal ArticleDOI
TL;DR: Evidence is provided that the D and L stereoisomers exhibit important cell type-specific variations in activity that support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-mediated immunosuppression and enhance antitumor immunity in the setting of combined chemo-immunotherapy regimens.
Abstract: Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquired tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being developed for clinical trials. However, 1-methyl-tryptophan exists in two stereoisomers with potentially different biological properties, and it has been unclear which isomer might be preferable for initial development. In this study, we provide evidence that the D and L stereoisomers exhibit important cell type-specific variations in activity. The L isomer was the more potent inhibitor of IDO activity using the purified enzyme and in HeLa cell-based assays. However, the D isomer was significantly more effective in reversing the suppression of T cells created by IDO-expressing dendritic cells, using both human monocyte-derived dendritic cells and murine dendritic cells isolated directly from tumor-draining lymph nodes. In vivo, the d isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamide, paclitaxel, or gemcitabine, when tested in mouse models of transplantable melanoma and transplantable and autochthonous breast cancer. The D isomer of 1-methyl-tryptophan specifically targeted the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a disruption of the IDO gene (IDO-knockout mice). Taken together, our findings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-mediated immunosuppression and enhance antitumor immunity in the setting of combined chemo-immunotherapy regimens.

573 citations

Journal ArticleDOI
01 Aug 2007-Obesity
TL;DR: The goal of this study was to evaluate the impact of a 10‐month after‐school physical activity program on body composition and cardiovascular fitness in young black girls.
Abstract: Objective: The goal of this study was to evaluate the impact of a 10-month after-school physical activity (PA) program on body composition and cardiovascular (CV) fitness in young black girls. Research Methods and Procedures: Subjects were 8- to 12-year-olds recruited from elementary schools. Body composition was measured using anthropometrics {waist circumference and BMI, DXA [percentage body fat (%BF)] and bone mineral density (BMD)}, and magnetic resonance imaging [visceral adipose tissue (VAT)]. CV fitness was measured using a graded treadmill test. The intervention consisted of 30 minutes homework/healthy snack time and 80 minutes PA (i.e., 25 minutes skills instruction, 35 minutes aerobic PA, and 20 minutes strengthening/stretching). Analyses were adjusted for age, baseline value of the dependent variable, and sexual maturation (pediatrician observation). Results: Mean attendance was 54%. Compared with the control group, the intervention group had a relative decrease in %BF (p < 0.0001), BMI (p < 0.01), and VAT (p < 0.01) and a relative increase in BMD (p < 0.0001) and CV fitness (p < 0.05). Higher attendance was associated with greater increases in BMD (p < 0.05) and greater decreases in %BF (p < 0.01) and BMI (p < 0.05). Higher heart rate during PA was associated with greater increases in BMD (p < 0.05) and greater decreases in %BF (p < 0.005). Discussion: An after-school PA program can lead to beneficial changes in body composition and CV fitness in young black girls. It is noteworthy that the control and intervention groups differed in change in VAT but not waist circumference. This suggests that changes in central adiposity can occur in response to PA, even in young children, but that waist circumference may not be a good indicator of central adiposity.

195 citations

Journal ArticleDOI
TL;DR: Children in intervention schools improved in fitness and %BF during the school years and returned to levels similar to those in control schools during the summers, highlighting the importance of year-round programs to promote healthy growth in youths.
Abstract: Objective. To evaluate the effect of a 3-year after-school physical activity (PA) intervention on aerobic fitness and percent body fat (%BF). Methods. In total, 18 schools were randomized into intervention or control arms. Measurements were made at the beginning and end of the third, fourth and fifth grades. Fitness was measured with heart rate response to a bench-stepping task.%BF and bone density were measured with dual-energy x-ray absorptiometry. The intervention included 40 min of academic enrichment activities, during which healthy snacks were provided, and 80 min of moderate-to-vigorous PA (MVPA). Results. Data analyses were performed on 206 youths who remained in the same schools for the 3-year period, who were measured at all six time points and, for the intervention group, who attended at least 40% of the sessions in each of the 3 years. The group by time interactions were significant for fitness (p < 0.01) and %BF (p < 0.05). Children in intervention schools improved in fitness and %BF during t...

187 citations

Journal ArticleDOI
TL;DR: Decisions made by incubating parents that influence egg temperature can modify incubation period and offspring phenotype, and Investigations of incubation as a reproductive cost should consider how parental decisions influence both parents and offspring.
Abstract: Summary 1Maternal effects often explain a significant amount of variation in offspring phenotype, and can be important in the evolution of life histories. Incubation of eggs is an important maternal effect, and optimal growth and development of avian embryos takes place within a narrow range of incubation temperatures, but the effect of incubation microclimate on neonate phenotype remains relatively unexplored in birds. 2In this study of Wood Ducks (Aix sponsa Linnaeus) we examined effects of incubation temperature on the length of incubation period and neonate quality. We monitored nest temperatures and incubation periods of naturally incubated Wood Duck nests and found a strong inverse relationship between incubation period and average nest temperature. 3Next, we collected three unincubated eggs from each of 48 nests, and randomly assigned eggs from each nest to one of three incubation temperatures (34·6, 36·0 and 37·4 °C). Experimental incubation temperatures overlapped average nest temperatures of naturally incubated Wood Duck nests. 4Hatching success varied with incubation temperature and was lowest for eggs incubated at the lowest temperature. Incubation period of experimental eggs decreased with increasing temperature but was not affected by fresh egg mass. 5Wood Duck embryos catabolized an estimated 34–38% of egg lipids and 25–33% of egg protein during incubation. Percentage change of lipids increased with decreasing incubation temperature, but not significantly. Embryos incubated at lower temperatures used a greater percentage of protein than embryos incubated at higher temperatures. 6In analyses using fresh egg mass as the covariate, we found that wet and dry mass of ducklings increased with increasing incubation temperature. Decreases in lipid content of Wood Duck neonates with decreasing incubation temperature were not significant, but eggs incubated at low temperatures produced ducklings that had reduced protein mass and that were structurally larger than ducklings from eggs incubated at high temperatures. 7Our study illustrates the importance of incubation temperature on the development of Wood Duck embryos. Decisions made by incubating parents that influence egg temperature can modify incubation period and offspring phenotype. Investigations of incubation as a reproductive cost should consider how parental decisions influence both parents and offspring.

170 citations

Journal ArticleDOI
TL;DR: Data indicate that aging and oxidative stress can significantly alter the miRNA cargo of EVs in the bone marrow microenvironment, which may in turn play a role in stem cell senescence and osteogenic differentiation by reducing Hmox1 activity.
Abstract: Microvesicle- and exosome-mediated transport of microRNAs (miRNAs) represents a novel cellular and molecular pathway for cell-cell communication. In this study, we tested the hypothesis that these extracellular vesicles (EVs) and their miRNAs might change with age, contributing to age-related stem cell dysfunction. EVs were isolated from the bone marrow interstitial fluid (supernatant) of young (3-4 months) and aged (24-28 months) mice to determine whether the size, concentration, and miRNA profile of EVs were altered with age in vivo. Results show that EVs isolated from bone marrow are CD63 and CD9 positive, and the concentration and size distribution of bone marrow EVs are similar between the young and aged mice. Bioanalyzer data indicate that EVs from both young and aged mice are highly enriched in miRNAs, and the miRNA profile of bone marrow EVs differs significantly between the young and aged mice. Specifically, the miR-183 cluster (miR-96/-182/-183) is highly expressed in aged EVs. In vitro assays demonstrate that aged EVs are endocytosed by primary bone marrow stromal cells (BMSCs), and these aged EVs inhibit the osteogenic differentiation of young BMSCs. Transfection of BMSCs with miR-183-5p mimic reduces cell proliferation and osteogenic differentiation, increases senescence, and decreases protein levels of the miR-183-5p target heme oxygenase-1 (Hmox1). In vitro assays utilizing H2O2-induced oxidative stress show that H2O2 treatment of BMSCs increases the abundance of miR-183-5p in BMSC-derived EVs, and Amplex Red assays demonstrate that H2O2 is elevated in the bone marrow microenvironment with age. Together, these data indicate that aging and oxidative stress can significantly alter the miRNA cargo of EVs in the bone marrow microenvironment, which may in turn play a role in stem cell senescence and osteogenic differentiation by reducing Hmox1 activity.

165 citations


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TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Abstract: Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

10,602 citations

Journal ArticleDOI
TL;DR: Variables that were consistently associated with children's physical activity were sex (male), parental overweight status, physical activity preferences, intention to be active, perceived barriers, previous physical activity, healthy diet, program/facility access, and time spent outdoors.
Abstract: SALLIS, J. F., J. J. PROCHASKA, and W. C. TAYLOR. A review of correlates of physical activity of children and adolescents. Med. Sci. Sports Exerc., Vol. 32, No. 5, pp. 963‐975, 2000. Background: Understanding the factors that influence physical activity can aid the design of more effective interventions. Previous reviews of correlates of youth physical activity have produced conflicting results. Methods: A comprehensive review of correlates of physical activity was conducted, and semiquantitative results were summarized separately for children (ages 3‐12) and adolescents (ages 13‐18). The 108 studies evaluated 40 variables for children and 48 variables for adolescents. Results: About 60% of all reported associations with physical activity were statistically significant. Variables that were consistently associated with children’s physical activity were sex (male), parental overweight status, physical activity preferences, intention to be active, perceived barriers (inverse), previous physical activity, healthy diet, program/facility access, and time spent outdoors. Variables that were consistently associated with adolescents’ physical activity were sex (male), ethnicity (white), age (inverse), perceived activity competence, intentions, depression (inverse), previous physical activity, community sports, sensation seeking, sedentary after school and on weekends (inverse), parent support, support from others, sibling physical activity, direct help from parents, and opportunities to exercise. Conclusion: These consistently related variables should be confirmed in prospective

4,382 citations

01 Sep 2008
TL;DR: The Methodology used to Prepare the Guideline Epidemiology Incidence Etiology and Recommendations for Assessing Response to Therapy Suggested Performance Indicators is summarized.
Abstract: Executive Summary Introduction Methodology Used to Prepare the Guideline Epidemiology Incidence Etiology Major Epidemiologic Points Pathogenesis Major Points for Pathogenesis Modifiable Risk Factors Intubation and Mechanical Ventilation Aspiration, Body Position, and Enteral Feeding Modulation of Colonization: Oral Antiseptics and Antibiotics Stress Bleeding Prophylaxis, Transfusion, and Glucose Control Major Points and Recommendations for Modifiable Risk Factors Diagnostic Testing Major Points and Recommendations for Diagnosis Diagnostic Strategies and Approaches Clinical Strategy Bacteriologic Strategy Recommended Diagnostic Strategy Major Points and Recommendations for Comparing Diagnostic Strategies Antibiotic Treatment of Hospital-acquired Pneumonia General Approach Initial Empiric Antibiotic Therapy Appropriate Antibiotic Selection and Adequate Dosing Local Instillation and Aerosolized Antibiotics Combination versus Monotherapy Duration of Therapy Major Points and Recommendations for Optimal Antibiotic Therapy Specific Antibiotic Regimens Antibiotic Heterogeneity and Antibiotic Cycling Response to Therapy Modification of Empiric Antibiotic Regimens Defining the Normal Pattern of Resolution Reasons for Deterioration or Nonresolution Evaluation of the Nonresponding Patient Major Points and Recommendations for Assessing Response to Therapy Suggested Performance Indicators

2,961 citations

Journal ArticleDOI
TL;DR: The effectiveness of a range of interventions that include diet or physical activity components, or both, designed to prevent obesity in children is evaluated to determine overall certainty of the evidence.
Abstract: The current evidence suggests that many diet and exercise interventions to prevent obesity in children are not effective in preventing weight gain, but can be effective in promoting a healthy diet and increased physical activity levels.Being very overweight (obese) can cause health, psychological and social problems for children. Children who are obese are more likely to have weight and health problems as adults. Programmes designed to prevent obesity focus on modifying one or more of the factors considered to promote obesity.This review included 22 studies that tested a variety of intervention programmes, which involved increased physical activity and dietary changes, singly or in combination. Participants were under 18 and living in Asia, South America, Europe or North America. There is not enough evidence from trials to prove that any one particular programme can prevent obesity in children, although comprehensive strategies to address dietary and physical activity change, together with psycho-social support and environmental change may help. There was a trend for newer interventions to involve their respective communities and to include evaluations.Future research might usefully assess changes made on behalf of entire populations, such as improvements in the types of foods available at schools and in the availability of safe places to run and play, and should assess health effects and costs over several years.The programmes in this review used different strategies to prevent obesity so direct comparisons were difficult. Also, the duration of the studies ranged from 12 weeks to three years, but most lasted less than a year.

2,464 citations