Homeostatic proliferation of B cells

Na?ve B cells introduced into a lymphopenic host undergo antigen-independent proliferation which is inhibited in a cell dose dependent manner by feedback from mature B cells. Homeostatic proliferation is a generalized lymphocyte property with B cells sharing many of the inductive and regulatory characteristics established for na?ve and memory CD4+ and CD8+ T cells and NK cells. In this communication we discuss the cytokine requirements for B cell HP, extend the murine studies to human cells, and propose the hypothesis that B cell HP may provide an antigen-independent mechanism for maintaining B cell memory.     

The Health Status of Hispanic Agricultural Workers in Georgia and Florida

To examine the health status of Hispanic agricultural workers in Florida and Georgia. Health data from agricultural workers in the Farm Worker Family Health Program (June 2019) and research studies in Florida (May 2015 and May 2019) were examined. Data from 728 agricultural workers were collected through sociodemographic questionnaire and clinical data. In the Florida sample, 83% were overweight or obese, 70% elevated blood pressure, 60% met the definition of prediabetes. In Georgia, 64% were overweight or obese and 67% had elevated blood pressure. Weak correlations were observed between BMI and systolic blood pressure (unadjusted r?=?0.20), diastolic blood pressure (unadjusted r?=?0.19), and glucose (unadjusted r?=?0.14). Adjusting for age and gender did not show statistically significant correlation between BMI and systolic and diastolic blood pressure or glucose. While BMI has been shown to be strongly associated with high blood pressure and impaired glucose, we found a weak correlation among agricultural workers. Given the common and high use of pesticides and elevated rates of hypertension, impaired glucose, and adiposity in agricultural workers, the public health impact of this relationship may require and lead to occupational reform that protects the health of agricultural workers. Future studies should assess occupational and environmental factors and lifestyle differences between agricultural workers and the general population to better understand these discrepancies in health status.

     

Acute effects of nicotine on hunger and caloric intake in smokers and nonsmokers

The inverse relationship between smoking and body weight may be due in part to nicotine's effects on reducing hunger and eating. Male smokers and nonsmokers (n=10 each), abstinent overnight from smoking and food, participated in four sessions, involving consumption of a liquid caloric load or water followed by nicotine (15 µg/kg) or placebo via nasal spray every 20 min for 2 h. Hunger and satiety (fullness) ratings were obtained prior to each dose presentation. At the end of the two sessions involving the caloric load (simulating breakfast), subjects were also presented with typical lunch/snack food items varying in sweet taste and fat content for ad lib consumption. Results indicated that, for both smokers and nonsmokers, the hunger-reducing effects of nicotine occurred only following caloric load consumption, and there was no effect of nicotine on hunger after water consumption. Smokers unexpectedly reported greater satiation than nonsmokers following the caloric load regardless of nicotine or placebo condition. Nicotine also resulted in less caloric intake during the meal, and the decrease was not specific to consumption of sweet, high-fat foods. These results indicate that nicotine reduces appetite, possibly helping to explain the influence of smoking on body weight.     

Future health of AYA survivors

Adolescent and young adult (AYA) oncology patients (ages 15–39) have been identified as a group with healthcare disparities including gaps and challenges in diagnosis, access to care, research, clinical trial participation, and cure rates. Like other patient groups with cancer or other chronic illnesses, disparities can lead to poor future health and outcomes, which is a well‐recognized concern within the AYA population. Cancer is the leading disease‐related cause of death in this age range. Numerous interested groups including the National Cancer Institute have met to address the research and cancer care needs of AYAs. This review highlights how these gaps in care during and after treatment can affect future health of this population of patients. Access to care, models of survivorship care, and lack of provider education are discussed. Survivorship care and use of guidelines, and promotion of psychosocial support and health behaviors during treatment and beyond are essential to optimizing future health of AYA patients.     

Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival

We investigated the mechanism by which B lymphocyte stimulator (BLyS)/BAFF, a tumor necrosis factor superfamily ligand, promotes B-cell survival and resistance to atrophy. BLyS stimulation activates 2 independent signaling pathways, Akt/mTOR and Pim 2, associated with cell growth and survival. BLyS blocks the cell volume loss (atrophy) that freshly isolated B cells normally undergo when maintained in vitro while concurrently increasing glycolytic activity and overall metabolism. This atrophy resistance requires Akt/mTOR. We used a genetic approach to resolve the contributions of Akt/mTOR and Pim kinase pathways to BLyS-mediated survival. Pim 2-deficient B cells are readily protected from death by BLyS stimulation, but this protection is completely abrogated by treatment with the mTOR inhibitor rapamycin. Furthermore, rapamycin treatment in vivo significantly reduces both follicular and marginal zone B cells in Pim-deficient but not healthy hosts. BLyS-dependent survival requires the antiapoptotic protein Mcl-1. Mcl-1 protein levels rise and fall in response to BLyS addition and withdrawal, respectively, and conditional deletion of the Mcl-1 gene renders B cells refractory to BLyS-mediated protection. Because BlyS is required for the normal homeostasis of all B cells, these data suggest a therapeutic strategy simultaneously inhibiting mTOR and Pim 2 could target pathogenic B cells.     

Prostacyclin analogs stimulate receptor-mediated cAMP synthesis and ATP release from rabbit and human erythrocytes

Objectives: The purpose of this study was to establish that the prostacyclin (PGI₂) receptor (IP receptor) is present on rabbit and human erythrocytes and that its activation stimulates cyclic adenosine monophosphate (cAMP) synthesis and adenosine triphosphate (ATP) release. Methods: The effect of incubation of erythrocytes with the active PGI₂ analogs, iloprost or UT‐15C, on cAMP levels and ATP release was determined in the absence and presence of the IP receptor antagonist, CAY10441. Western analysis was used to determine the presence of the IP receptor on isolated membranes. To establish that effects of PGI₂ analogs were not due to prostaglandin E₂(PGE₂) receptor activation, the effect of PGE₂ on cAMP levels and ATP release was determined. Results: Rabbit and human erythrocytes possess IP receptors. Iloprost and UT‐15C stimulated increases in cAMP and ATP release that were prevented by the IP receptor antagonist, CAY10441. PGE₂ did not stimulate cAMP accumulation or ATP release and did not inhibit iloprost‐induced increases in cAMP. Conclusions: This study establishes that the IP receptor is present on rabbit and human erythrocytes and that its activation results in increases in cAMP and ATP release. These results suggest a novel mechanism by which PGI₂ and its active analogs, when administered pharmacologically, could produce vasodilation.     

Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation

Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis. We propose that environmental factors (pesticides and infections) increase the risk for iPD via the immune system and that the role of PD risk genes in immune cells is worthy of investigation. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and, alone or in combination with other factors, may contribute to iPD pathogenesis. By reviewing these interactions, we seek to enable the future development of immunomodulatory approaches to prevent or delay onset of iPD. © 2020 International Parkinson and Movement Disorder Society