Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients

In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum and liver of patients with the obesity-associated malignancy oesophageal adenocarcinoma (OAC). Furthermore, we assessed the secreted cytokine profile in OAC patient serum, omentum and liver to assess systemic and local inflammation. We observed parallel T cell cytokine profiles and phenotypes in the omentum and liver of OAC patients, in particular CD69+ and inflammatory effector memory T cells. This study reflects similar processes of inflammation and T cell activation in the omentum and liver, and may suggest common targets to modulate pathological inflammation at these sites

Missio Apostolica Special CHS Partnership Issue

Confessing Christ contextually has been one of the emphases of this Journal since its inception fifteen years ago. Our readership has experienced the joy of missionaries sharing the faith with various peoples and cultures in domestic as well as distant lands. Colleague Leo Sanchez has provided us personnel as well as resources to publish this edition with an emphasis on mission and ministry among the Hispanic/Latino population of God‘s world. An added feature in this issue is summary statements of the articles in Spanish. This issue is comprehensive in its scope as it presents topics and voices such as Marginality and the Hispanic Church, Latino Church Planting, Latino Lutheran Identity, Women, and actual eyewitness testimonies of Hispanic work on our shores. These are exciting times for churches and institutions that prepare men and women for God‘s mission in a world overpowered by the multiplicity of cultures, and plurality of religions and worldviews. Our readers will know how

The Political Economy of the Hospital in History

The modern hospital is at once the site of healing, the locus of medical learning and a cornerstone of the welfare state. Its technological and infrastructural costs have transformed health services into one of today's fastest growing sectors, absorbing substantial proportions of national income in both developed and emerging economies. The aim of this book is to examine this growth in different countries, with a main focus on the twentieth century, and also with a backward glance to earlier shaping forces. It will explore the hospital's economic history, the relationship between public and private forms of provision, and the political context in which health systems were constructed. The collection advances the historical world map of different hospital models, ranging across Spain, Brazil, Germany, East and Central Europe, Britain, the United States and China. Collectively, these comparative cases illuminate the complexities involved in each country and bring new historical evidence to current debates on health care organisation, financing and reform

The Grizzly, February 6, 1996

Hinojosa Smith\u27s Sense of Place • Will Keim Speaks to Greeks • Du Pont: All the Facts • Political Gibberish • Selling the American Dream • Sculptures on Display at Berman Museum • Michael Cochrane Quartet to Perform • The Piano Man Plays Trenton State College • Bears Set Scoring Record • Men and Women\u27s Teams Endure Tough Week • The Ursinus Mascot: Part 2 • Men\u27s Hoop Team Defeats Muhlenberg 80-71 • Bears Defeat Haverford, Trounce Delaware Valleyhttps://digitalcommons.ursinus.edu/grizzlynews/1373/thumbnail.jp

The Microenvironment of Visceral Adipose Tissue and Liver Alter Natural Killer Cell Viability and Function

The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-α+ and NKP46+ NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role

The Grizzly, January 30, 1996

The Ruby is Dead • Research Conference Originates at Ursinus • The Soul of the Matter • Ursinus Recital Featured Two Organists • The Ursinus Blackout • Heefner Organ Recital Series Kicks Off • The Bear Facts About the Ursinus Mascot: Part 1 • Study Abroad: More Than Just an Academic Experience • Women\u27s Hoops Struggling • Bears In Thick of Playoff Race • Anecdotes of a Wagon Lost in Denver • Bears Nationally Ranked • Bears Look Tough to Beat as Centennial Tourney Hostshttps://digitalcommons.ursinus.edu/grizzlynews/1372/thumbnail.jp

Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8(+) T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients

The omentum is enriched with pro-inflammatory effector memory CD8+ T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8+ T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8+ T cells expressing intermediate levels (CX3CR1INT) are defined as peripheral memory, those expressing the highest levels (CX3CR1HI) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1NEG) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8+ T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8+ T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8+ T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1INT and CX3CR1HI CD8+ T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8+ T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1NEG CD8+ T cells express higher levels of L-selectin than CX3CR1INT CD8+ T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1INT CD8+ T cells to a CX3CR1NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8+ T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maintenance of the CX3CR1NEG CD8+ T cell populations