C-Reactive Protein and Vulnerability to Mental Stress-Induced Myocardial Ischemia Rahman Shah, Matthew M Burg, Aseem Vashist, Dorothea Collins, Joyce Liu, Farid Jadbabaie, Brendon Graeber, Christine Earley, Rachel Lampert, and Robert Soufer Myocardial ischemia provoked in the laboratory during mental stress (MSI) in patients with stable coronary artery disease (CAD) predicts subsequent clinical events. The pathophysiology of MSI differs from that of exercise ischemia, and the mechanisms tying MSI to poor prognosis are not known. C-reactive protein (CRP) is a risk marker for cardiovascular events in patients with CAD, but little is known regarding the relationship of CRP to MSI. Here, Shah et al. (269-274) studied 83 subjects with stable coronary artery disease to examine the association of C-reactive protein to MSI. The authors found that CRP levels correlate with myocardial ischemia raising the possibility that CRP may be a risk marker of MSI in patients with coronary artery disease. Page 269 View article: PDF (100 KB) HTML
Neovascularization of Ischemic Myocardium by Newly Isolated Tannins Prevents Cardiomyocyte Apoptosis and Improves Cardiac Function Xuemei Gu, Lei Cheng, Winghong L Chueng, Xinsheng Yao, Hongwei Liu, Guoqing Qi, and Ming Li Ischemic heart disease is a leading cause of morbidity and mortality in many countries. Restoration of coronary blood flow by rapid angiogenesis may offer a direct and effective therapeutic modality for intractable ischemic heart disease. While therapeutic angiogenesis using growth factors has been intensely studied, these factors take anywhere from days to weeks to act. There is no treatment currently available which promotes early reconstitution of the damaged vasculature with newly formed vessels. Here, Gu et al. (275-283) show that extracts isolated from the Chinese herb Geum japonicum exhibit healing effects on infarcted myocardium by stimulating early growth of new blood vessels and preventing apoptosis in the at-risk myocardium adjacent to the infarct zone. This finding may provide a new therapeutic approach in the field of therapeutic angiogenesis for the treatment of ischemic heart disease. Page 275View article: PDF (792 KB) HTML
Morphine Reciprocally Regulates IL-10 and IL-12 Production by Monocyte-derived Human Dendritic Cells and Enhances T Cell Activation Davorka Messmer, Ikusuke Hatsukari, Naoko Hitosugi, Ingo G H Schmidt-Wolf, and Pravin C Singhal While our understanding of the role of opiates in the modulation of immunity has expanded, the direct effect of morphine on immunity remains enigmatic. Opiate addicts are prone to infection often attributed to immunomodulatory effects and chronic administration affects both innate and adaptive immunity. There is growing evidence that opioid receptors are expressed by cells of the immune system and may modulate immune responses. Dendritic cells play a central role in the initiation and control of the adaptive immune response. Here, Messmer et al. (284-290) investigate the effects of morphine on the differentiation process of human myeloid dendritic cells from monocytes. Results indicate that the signals for pain and immunomodulation are intricately linked. These data advance our understanding of the mechanism of opiates in the adaptive immune response. Page 284 View article: PDF (276 KB)HTML
Glucocorticoids and TNFα Interact Cooperatively to Mediate Sepsis-Induced Leucine Resistance in Skeletal Muscle Charles H Lang and Robert A Frost
Alternatives in protein metabolism during sepsis include both decreased protein synthesis as well as increased protein degradation, resulting in weight loss during the course of the disease. Leucine availability represents an important nutritional signal responsible for postprandial stimulation of muscle protein synthesis. Sepsis blunts leucine’s nutrient signaling ability by impairing the initiation of translation, resulting in decreased skeletal muscle protein synthesis. Here Lang and Frost (291-299) test whether overproduction of the catabolic mediators, tumor necrosis factor alpha (TNFα) or glucocorticoids, mediate sepsis-induced leucine resistance. Results demonstrate that sepsis-induced leucine resistance in skeletal muscle results from the cooperative interaction of both TNFα and glucocorticoids. These findings extend the knowledge base surrounding sepsis-induced leucine resistance and may initiate therapeutic approaches targeting both catabolic mediators simultaneously. Page 291 View article: PDF (512 KB) HTML
Similarities and Differences Between the Light and Heavy Chain Ig Variable Region Gene Repertoires in Chronic Lymphocytic Leukemia Fabio Ghiotto, Franco Fais, Emilia Albesiano, Cristina Sison, Angelo Valetto, Gianluca Gaidano, Janine Reinhardt, Jonathan E Kolitz, Kanti Rai, Steven L Allen, Manlio Ferrarini, and Nicholas Chiorazzi Analyses of immunoglobulin (Ig) VHDJH rearrangements expressed by B-CLL cells have provided insights into the antigen receptor repertoire and maturation stages of B-lymphocytes that give rise to disease. As Ig variable (V) domains are the components of the B-cell antigen receptor that interact with antigen, the analyses of gene segments that encode these domains can provide indirect information about the structure of the B-cell antigen receptor. Ghiotto et al. (300-308) analyzed the VL and JL gene segments of 206 B-CLL patients, paying particular attention to the frequency of use and association, mutation status, and LCDR3 characteristics. The similarities and differences observed between the IgH and IgL V gene repertoires expressed in B-CLL suggest some novel features while also reinforcing concepts derived from studies of the IGH repertoire. Page 206 View article: PDF (92 KB) HTML
The CD38 Ectoenzyme Family: Advances in Basic Science and Clinical Practice
The function of the mammalian immune system is to detect and destroy foreign antigens from viruses, bacteria and other exogenous sources; as well as dysfunctional or aberrant endogenous antigens, such as cancer cells. In this capacity, cells of the immune system can have highly lethal effects on its targets, a characteristic that allows rapid and efficient clearance of undesired cells, microorganisms, and antigens. Left uncontrolled, however, these lethal activities can have adverse effects on normal cells and tissues, causing pathologies ranging from rheumatoid arthritis, inflammatory bowel disease and septic shock, to lupus, myeloma and leukemia. In order to maintain the proper balance between healthful and harmful immune responses, the cells of the immune system rely on complex direct and indirect interactions that are mediated in part through cell surface molecules including some known as cellular differentiation (CD) markers. Over 500 leukocyte CD markers have been characterized to date. These surface proteins serve as the interface between the immune cells and their environment, and occupy a central role in transducing intracellular signals that regulate cellular activities. Among these cell surface proteins are two members of a family of cyclases that metabolize nicotinic adenine dinucleotide (NAD+) into nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic adenosine dinucleotide phosphate-ribose (cADPR), and are potent modulators of the immune system. These two ectoenzymes, known as CD38 and CD157, have been the focus of much research into the biology of the immune system. Research being conducted by molecular biologists, protein chemists, immunologists and clinicians has generated a better understanding of the biological functions of the CD38 family of ectoenzymes, and their roles in health and disease. Discoveries in basic biology, combined with clinical observations and ground-breaking translational research, are setting the stage for targeted therapeutics, and fulfilling the mission of molecular medicine. As presented at the Torino CD38 Meeting, the culmination of these efforts is the identification of these ectoenzymes as potential new therapeutic targets or diagnostic markers for myleoma and leukemia. View Full Supplement: PDF (576 KB) HTML
Supplement Mini-Reviews CD38 and CD157: Biological Observations to Clinical Therapeutic Targets Amy Warenda Czura and Christopher J Czura View article: PDF (230 KB)HTML
Medical Applications of Leukocyte Surface Molecules— the CD molecules Heddy Zola
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Structure and Enzymatic Functions of Human CD38 Hon Cheung Lee
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Emerging Functions of Extracellular Pyridine Nucleotides Richard A Billington, Santina Bruzzone, Antonio De Flora, Armando A Genazzani, Friedrich Koch-Nolte, Mathias Ziegler, and Elena Zocchi View article: PDF (268 KB)HTML
Signaling Properties of CD38 in the Mouse Immune System:Enzyme-dependent and -independent Roles in Immunity Frances E Lund View article: PDF (172 KB)HTML
CD38 and CD157 as Receptors of the Immune System: A Bridge Between Innate and Adaptive Immunity Fabio Malavasi, Silvia Deaglio, Enza Ferrero, Ada Funaro, Jaime Sancho, Clara M Ausiello, Erika Ortolan, Tiziana Vaisitti, Mercedes Zubiaur, Giorgio Fedele, Semra Aydin, Elena V Tibaldi, Ilaria Durelli, Riccardo Lusso, Franco Corzo, and Alberto L Horenstein
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The CD38 Ectoenzyme Family: Advances in Basic Science and Clinical Practice Fortunato Morabito, Rajendra N Damle, Silvia Deaglio, Michael Keating, Manlio Ferrarini, and Nicholas Chiorazzi
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CD38 as a Therapeutic Target George T Stevenson
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