Medical Nutrition Commons^™

Gut Microbiome Composition Is Linked To Whole Grain-Induced Immunological Improvements, Ines Martinez, James M. Lattimer, Kelcie L. Hubach, Jennifer A. Case, Junyi Yang, Casey G. Weber, Julie A. Louk, Devin J. Rose, Gayaneh Kyureghian, Daniel A. Peterson, Mark D. Haub, Jens Walter

Food for Health: Publications

The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on …

Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz

Food for Health: Publications

Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …

Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Biochemistry and Microbiology

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Disparate Degrees Of Hypervariable Loop Flexibility Control T Cell Receptor Cross-Reactivity, Specificity, And Binding Mechanism, Daniel R. Scott, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Steven A. Corcelli, Brian M. Baker

Food for Health: Publications

αβ T cell receptors recognize multiple antigenic peptides bound and presented by major histocompatibility complex molecules. TCR cross-reactivity has been attributed in part to flexibility of the complementarity-determining region loops, yet there have been limited direct studies of loop dynamics to determine the extent of its role. Here we studied the flexibility of the binding loops of the αβ TCR A6 utilizing crystallographic, spectroscopic, and computational methods. A significant role for flexibility in binding and cross-reactivity was indicated only for the CDR3α and CDR3β hypervariable loops. Examination of the energy landscapes of these two loops indicated that CDR3β possesses a …

Identification And Engineering Of Human Variable Regions That Allow Expression Of Stable Single-Chain T Cell Receptors, David H. Aggen, Adam S. Chervin, Francis K. Insaidoo, Kurt H. Piepenbrink, Brian M. Baker, David M. Kranz

Food for Health: Publications

Single-chain antibody fragments (scFv), consisting of two linked variable regions (V_H and V_L), are a versatile format for engineering and as potential antigen-specific therapeutics. Although the analogous format for T cell receptors (TCRs), consisting of two linked V regions (Vα and Vβ; referred to here as scTv), could provide similar opportunities, all wild-type scTv proteins examined to date are unstable. This obstacle has prevented scTv fragments from being widely used for engineering or therapeutics. To further explore whether some stable human scTv fragments could be expressed, we used a yeast system in which display of properly folded …

Fluorine Substitutions In An Antigenic Peptide Selectively Modulate T Cell Receptor Binding In A Minimally Perturbing Manner, Kurt H. Piepenbrink, Oleg Y. Borbulevych, Ruth F. Sommese, John Clemens, Kathrynq M. Armstrong, Clare Desmond, Priscilla Do, Brian M. Baker

Food for Health: Publications

T cell receptor (TCR) recognition of antigenic peptides bound and presented by major histocompatibility complex (MHC) molecules forms the basis of the cellular immune response to pathogens and cancer. TCRs bind peptide/MHC molecules weakly and with fast kinetics, features which have hindered detailed biophysical studies of these interactions. Modified peptides resulting in enhanced TCR binding could help overcome these challenges. Further, there is considerable interest in using modified peptides with enhanced TCR binding as the basis for clinical vaccines. Here, we studied how fluorine substitutions in an antigenic peptide can selectively impact TCR recognition. Using a structure-guided design approach, we …

Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman

Biochemistry and Microbiology

Background: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of …

Algal Biofuel, Feb. 12, 2010, Harry Reid Center, University Of Nevada, Las Vegas

Biofuels

News in Brief

1. Fatty Acids Protect Against Aging (Feb. 8, 2010)

T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker

Food for Health: Publications

Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were …

Kelly, Rita Helen Roberts (Fa 353), Manuscripts & Folklife Archives

Folklife Archives Finding Aids

Finding aid and full-text scan of paper (Click on “Additional Files” below) for Folklife Archives Project 353. Paper: "Good Mothering through Breast Feeding: Observations of a Meeting of the La Leche League" written by Rita H. Kelly for a Western Kentucky University folk studies class.

Conformational Changes And Flexibility In T-Cell Receptor Recognition Of Peptide–Mhc Complexes, Kathryn M. Armstrong, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

A necessary feature of the immune system, TCR (T-cell receptor) cross-reactivity has been implicated in numerous autoimmune pathologies and is an underlying cause of transplant rejection. Early studies of the interactions of αβ TCRs (T-cell receptors) with their peptide–MHC ligands suggested that conformational plasticity in the TCR CDR (complementarity determining region) loops is a dominant contributor to T-cell cross-reactivity. Since these initial studies, the database of TCRs whose structures have been solved both bound and free is now large enough to permit general conclusions to be drawn about the extent of TCR plasticity and the types and locations of motion …

Sr-Bi Protects Against Endotoxemia In Mice Through Its Roles In Glucocorticoid Production And Hepatic Clearance, Lei Cai, Ailing Ji, Frederick C. De Beer, Lisa R. Tannock, Deneys R. Van Der Westhuyzen

Internal Medicine Faculty Publications

Septic shock results from an uncontrolled inflammatory response, mediated primarily by LPS. Cholesterol transport plays an important role in the host response to LPS, as LPS is neutralized by lipoproteins and adrenal cholesterol uptake is required for antiinflammatory glucocorticoid synthesis. In this study, we show that scavenger receptor B-I (SR-BI), an HDL receptor that mediates HDL cholesterol ester uptake into cells, is required for the normal antiinflammatory response to LPS-induced endotoxic shock. Despite elevated plasma HDL levels, SR-BI–null mice displayed an uncontrollable inflammatory cytokine response and a markedly higher lethality rate than control mice in response to LPS. In addition, …

Plasma Total Homocysteine And The Effect Of B-Group Vitmains. Current Knowledge And Future Directions In Assessment For Cardiovascular Diseases Among U.S. Cardiovascular Specialists, Salam F. Sunna

All-Inclusive List of Electronic Theses and Dissertations

Cardiovascular disease remains the major cause of morbidity and mortality in the United States claiming the lives of over 40% of the nearly 2.4 million Americans who die each year. Recent studies have shown that elevated homocysteine in the blood is related to a higher risk of coronary heart disease, peripheral vascular disease and stroke independent of other classical cardiovascular disease risk factors. The aim of this study is to determine the general awareness and acceptance of U.S. cardiovascular specialists of the homocysteine theory, the criteria used for ordering a homocysteine test, the frequency physicians refer patients to dietitians for …

Hdl-Associated Estradiol Stimulates Endothelial No Synthase And Vasodilation In An Sr-Bi–Dependent Manner, Ming Gong, Melinda E. Wilson, Thomas Kelly, Wen Su, James Dressman, Jeanie Kincer, Sergey V. Matveev, Ling Guo, Theresa Guerin, Xiang-An Li, Weifei Zhu, Annette M. Uittenbogaard, Eric J. Smart

Pediatrics Faculty Publications

Cardiovascular diseases remain the leading cause of death in the United States. Two factors associated with a decreased risk of developing cardiovascular disease are elevated HDL levels and sex — specifically, a decreased risk is found in premenopausal women. HDL and estrogen stimulate eNOS and the production of nitric oxide, which has numerous protective effects in the vascular system including vasodilation, antiadhesion, and anti-inflammatory effects. We tested the hypothesis that HDL binds to its receptor, scavenger receptor class B type I (SR-BI), and delivers estrogen to eNOS, thereby stimulating the enzyme. HDL isolated from women stimulated eNOS, whereas HDL isolated …

Hiv Protease Inhibitors Promote Atherosclerotic Lesion Formation Independent Of Dyslipidemia By Increasing Cd36-Dependent Cholesteryl Ester Accumulation In Macrophages, James Dressman, Jeanie Kincer, Sergey V. Matveev, Ling Guo, Richard N. Greenberg, Theresa Guerin, David Meade, Xiang-An Li, Weifei Zhu, Annette M. Uittenbogaard, Melinda E. Wilson, Eric J. Smart

Physiology Faculty Publications

Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor–dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upregulation of CD36 and the accumulation of cholesteryl esters. The use of CD36-blocking antibodies, a CD36 morpholino, and monocytes isolated from CD36 null mice demonstrated that protease inhibitor–induced increases in cholesteryl esters were dependent on CD36 upregulation. These data led to the hypothesis that protease inhibitors induce foam cell formation and consequently atherosclerosis by upregulating CD36 and …

The Role Of Diet And Physical Activity For Ovarian Cancer Results From The Adventist Health Study, Fatemeh Kiani

Loma Linda University Electronic Theses, Dissertations & Projects

A few aspects of the epidemiology of ovarian cancer are well understood, such as the inverse relationship with parity and oral contraceptive (OC) use. The role of other factors such as the potential influence of diet or physical activity is far from being established. A few studies, however, have been able to identify dietary risk factors for ovarian cancer. In this dissertation, I have conducted two studies that investigate the relationship between dietary factors and physical activity and the three endpoints: 1) nonfatal ovarian cancer (1976-1982; time to diagnosis), 2) fatal ovarian cancer (1976-1988; time to death), and 3) total …

The Influence Of Low Dietary Fat Intake On Incidence And Severity Of Migraine Headache, Zuzana Bic

Loma Linda University Electronic Theses, Dissertations & Projects

Migraine headaches are a common and debilitating syndrome causing untold suffering and loss of productivity. A review of the literature indicates that there are two primary factors involved in triggering these headaches: high levels of blood lipids and high levels of free fatty acids. Under these conditions platelet aggregability is increased, which is associated with decreases in serotonin and heightened prostaglandins levels. These conditions may produce vasodilation, the most immediate precursor to migraine headache. A high fat diet is one factor that may directly affect this process. This study was undertaken to evaluate the impact of dietary fat intake on …

Maternal-Neonatal Serum Vitamin A Concentrations., Girish S. Shirali, D G. Oelberg, K P. Mehta

Manuscripts, Articles, Book Chapters and Other Papers

Prevention of neonatal vitamin A deficiency is related to the adequacy of maternal vitamin A stores. In this study we investigated maternal and cord serum vitamin A and retinol-binding protein (RBP) values in an Indian population including, for the first time, clinically vitamin A-deficient mothers. Twenty-eight maternal-neonatal pairs were selected from maternal cohorts of high socioeconomic status without clinical evidence of vitamin A deficiency (group I) and low socioeconomic status with conjunctival xerosis and Bitot's spots (group II). Maternal education, caloric and vitamin A intakes, weight, height, hemoglobin, and birth weight were significantly lower in group II. Serum vitamin A …

Lipoprotein Lipase Inhibitor Removal During Ultrafiltration Of Renal Failure Patients, Alisa Minear

Loma Linda University Electronic Theses, Dissertations & Projects

Plasma samples were obtained from seven hypertriglyceridemic (>150 mg/dl) chronic renal failure patients before and after regular hemodialysis. The effect of the plasma on the lipolytic activity of bovine milk lipoprotein lipase was investigated. The lipoprotein lipase activity, as measured by release of C¹⁴-labeled free fatty acid from triglyceride, was decreased 8-67% when incubated with uremic plasma as compared to the control plasma (44 mg/dl triglyceride). The inhibition noted prior to hemodialysis did not appear to be alleviated by the dialysis but subsequent treatment with an isolated ultrafiltration technique did appear to remove an inhibitory substance as …