- Email: [email protected]
Foreword: Special Issue Cruse Festschrift
Experimental and Molecular Pathology 93 (2012) 285–287
Contents lists available at SciVerse ScienceDirect
Experimental and Molecular Pathology journal homepage: www.elsevier.com/locate/yexmp
Foreword
Foreword: Special Issue Cruse Festschrift
It is a pleasure and privilege to express genuine appreciation to the invited authors and their colleagues who have prepared the articles in this Festschrift honoring Dr. Julius Cruse. All have been associated professionally in some way or another with Dr. Cruse. Their generous decision to share premier research from their laboratories in the Festschrift attests to the high regard in which they hold the honoree. We are profoundly grateful to Elsevier Publishers for their generous support of this Festschrift for Dr. Cruse. Invited Principal Investigators and their colleagues: ▪ Professor Noel R. Rose, MD, PhD, The Johns Hopkins University, Baltimore, MD ▪ Professor Nicole Suciu-Foca, PhD, George Vlad, PhD, Columbia University College of Physicians and Surgeons, New York, NY ▪ Professor Maximilian Buja, MD, Priya Weerasinghe, MD, PhD, University of Texas Health Science Center, Houston, TX ▪ Professor Samuel French, MD, PhD, Dr. Barbara A. French, Joan Oliva, PhD, Jun Li, MD, Fawzia Bardag-Gorce, PhD, Brittany Tillman, student, Allon Canaan, MD, Harbor UCLA Medical Center, Torrance, CA ▪ Professor Olivera J. Finn, PhD, University of Pittsburgh Medical Center, Pittsburgh, PA ▪ Professor Peter Ward, MD, Drs. Markus Bosmann, Norman F. Russkamp, University of Michigan Medical Center, Ann Arbor, MI ▪ Professor Mark I. Greene, MD, PhD, FRCP, Aaron Runkle, PhD; Drs. Hongtao Zhang, Zheng Cai, Zhigiang Zhu, Barry L. Karger, Shiaw-lin Wu, Donald M. O'Rourke, Zhaocai Zhou, Qiang Wang; Drs Guoping Deng, Yan Xiao, Zhaocai Zhou, Yasuhiro Nagai, Hongtao Zhang, Bin Li, University of Pennsylvania Medical Center, Philadelphia, PA ▪ Professor Gregory Tsongalis, PhD, Cocay A. Rauwerkink, MD, Tor D. Tosteson, PhD; John M. Hill, MD, Kenneth R. Meehan, MD, PhD, Geisel School of Medicine at Dartmouth, Hartford, CT ▪ Professor Daniel S. Longnecker, MD, Michael Baker, MD, E. Scott Seeley, MD, PhD, Reetesh Pai, MD, Arief Suriawinata, MD, Mari Mino-Kenudson, MD; Giuseppe Zamboni, MD, Günter Klöppel, MD, Texas Children's Hospital, Baylor College of Medicine, Houston, TX ▪ Professor Ian Mackay 1, MD, Monash University, Victoria, Australia ▪ Professor Melvin Cohn, PhD, Salk Institute, La Jolla, CA ▪ Professor D. Radford Shanklin, MD, Marine Biological Laboratory, Woods Hole, MA ▪ Professor Thalachallour Mohanakumar, PhD, Drs. Nayan Sarma, Venkataswarup Tiriveedhi, Sabarinathan Ramachandran, Jeffrey Crippin, William Chapman, Washington University Medical Center, St. Louis, MO ▪ Professor Yehuda Shoenfeld, MD, PhD, Drs. Yinon Shapira, Nancy 1 Autoimmune Hepatitis: What Must be Said will appear in an upcoming regular issue of the journal even though it is a part of this Festschrift.
0014-4800/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yexmp.2012.10.017
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Agmon-Levin, Yves Renaudineau, Bat Sheve Porat-Katz, Ori Barzilai, Maya Ram, and Pierre Youinou, Sheba Medical Center, Tel-Aviv University, Tel-Aviv, Israel Professor William Coleman, PhD, and Dr Ashley G. Rivenbach, senior author, University of North Carolina Medical Center, Chapel Hill, NC Dr. Dimiter Dimitrov, MD, PhD, Drs. Parbakaran Ponraj, Ponraj Prabakaran, Zhongyu Zhu, Yang Feng, Emily D. Streaker, National Institutes of Health, Bethesda, MD Professor Santa Ono, PhD, Drs. Chuan-Hui Kuo, Kei Morohoshi, Cho Cho Aye, Robert B. Garoon, Andrea Collins, University of Cincinnati Medical Center, Cincinnati, OH Professor A. Bennett Jenson, MD, Shin J. Ghim, PhD, Joongho Joh, PhD; Mary Proctor, DVM; Arvind Ingle, MVSc, DICVP; Kathleen A. Silva; Christopher S. Potter, PhD; John P. Sundberg, PhD, DVM; Brown Cancer Center, University of Louisville Medical Center, Louisville, KY Professor Ramesh Gupta, PhD, Drs Afsoon Moktar, senior author, Srivani Ravoori, Manicka Vachanam, Jianmin Pan, Shesh Rai, Alfred Jenson, and Lyn Parker, University of Louisville Medical Center, Louisville, KY Professor A. M. Rostami, MD, PhD, Farinaz Safavi, MD, PhD, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA Professor Christian Koch, MD, Drs. Eugen Melcescu, Reed Hogan, Keith Brown, Stewart A. Boyd, Thomas L. Abell, University of Mississippi Medical Center, Jackson, MS Professor David Kaufman, MD, PhD, Scott Schlemmer, PhD, University of North Carolina, Chapel Hill, NC Professor Dr med. habil. Martin Zeitz, Drs. Tim Meyer, Reiner Ullrich, Charité Universität, Berlin Professor Annerose Berndt, PhD, Dr. Timothy M. Stearns, Clinton L. Cario, MD, Dr. Holly S. Savage, Beverly Paigen, PhD, John P. Sundberg, DVM, PhD, University of Pittsburgh School of Medicine, Pittsburgh, PA
As Festschrift Editor, I have provided an introductory article highlighting a few details of Dr. Cruse's life and work, as medical educator, editor, author, researcher and mentor. In honoring the lifetime achievements of Julius Cruse, Professor Noel Rose, the Father of Autoimmunity, and a friend of Dr. Cruse for 54 years, relates some of his personal experiences as an eyewitness and key participant in the history of modern immunology. He presents his views of the future in areas in which Professor Cruse has made lasting contributions, i.e. the history of science and scientific communication. Professor Rose indicates that we can “chart the future best by understanding the past”. The article by Professor Nicole Suciu-Foca and senior author, Dr. George Vlad, presents an elegant investigation on the induction of
286
Foreword
antigen-specific human T supressor cells by membrane and soluble immunoglobulin-like transcript 3 (ILT3). Their findings lead them to postulate that ILT3-Fc may become a valuable new therapy for autoimmunity and transplant rejection. Dr. Priya Weerasinghe and Professor Maximilian Buja present a fascinating review on oncosis: an overlooked and important alternative mode of cell death that is different from the type of programmed cell death known as apoptosis. Whereas, apoptosis is characterized by cell shrinkage followed by disintegration, oncosis is associated with cell swelling and cytoplasmic coagulation. The authors elaborate on this novel form of in vitro and in vivo cell death and review its multiple morphologic and biochemical features. They also allude briefly to its role in disease. In their continuing investigation of aggresomes, known as MalloryDenk bodies (MDB), Professor Samuel French and his colleagues investigated whether FAT10 or IFNγ are essential for MDB formation. They fed IFNγ and FAT10 knockout mice DDC added to the control diet. They found that IFNγ KO mice, but not FAT10 KO mice, developed MDB. Thus, they demonstrated that FAT10 is requisite to induce MDB formation in DDC fed mice. Professor Olja Finn presents an elegant and insightful analysis of the host immune response to neoplasia and the advent of novel and innovative cooperative approaches by an alliance between immunologists and pathologists to apply monoclonal antibodies and immunohistochemistry to not only reach a diagnosis and prognosis but also to characterize the tumor cells and their microenvironment to gauge the host response to the neoplasm. This joint approach by immunologists and pathologists, known as “Immunoscore”, assesses the contribution of the tumor microenvironment to prognosis. It is expected to not only facilitate research in both pathology and immunology but also to benefit patients, as well. Professor Peter Ward and co-investigators, Dr. Markus Bosmann, senior author, and Dr. Norman Russkamp's in-depth studies have shed light on the pathogenesis of endotoxin-induced inflammation. Multiplexing bead-based assays were used to define responses in two murine models of in vivo challenge intraperitoneally (endotoxemia) or intratracheally (acute lung injury) with LPS. The time course of 20 inflammatory mediators in plasma or bronchoalveolar lavages was analyzed. Their results, including the current article on fingerprinting of TLR4-induced inflammatory responsiveness, have elucidated and defined the host immune response to endotoxin. Although all mediators were induced, variations in concentrations, cytokine chemokine patterns and other parameters were noted when endotoxemia and LPS-ALI were compared. Professor Mark Greene, a Senior Editor of this journal, has generously provided two research contributions from his laboratory. The first, together with senior author of the article, Dr. Aaron Runkle, and colleagues, concerns reversion of the ErbB malignant phenotype and the DNA damage response. They review contemporary understanding of ErbB signaling and DNA double strand break repair. In the second article from Professor Greene's laboratory, he and senior author of the article, Dr. Guoping Deng, and associates, discuss the role of regulatory T cells in preventing host autoimmune diseases and limiting excessive immune responses to pathogens. They elucidate the molecular and biological role of the FOXP3 N-terminal domain in immune regulation of T regulatory/supressor cells. Professor Gregory Tsongalis, Dr. Cocav Rauwerdink, senior author, and associates present a clear and informative account on the practical application of chimerism analyses in allogeneic stem cell transplant recipients and conclude that PCR-based chimerism analyses using blood provide similar information to that obtained by marrow aspirate analyses. Dr. Michael Baker, Professor Daniel Longnecker and colleagues present an instructive and enlightening review of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms of the pancreas, which have been included and intermixed in some previous
papers on pancreatic cystic neoplasms. The authors investigated whether or not the earlier concept that mucinous cystic neoplasms occasionally progress to invasive colloid carcinoma. They found no examples of colloid carcinomas associated with 291 MCN. Focal expression of CDX2, an intestinal differentiation marker, was identified in some. Their results suggest that MCN only very infrequently, if ever, invade as colloid carcinoma. These investigators conclude that most malignant mucinous cystic neoplasms invade with a tubular or ductal pattern. Professor Ian Mackay, a pioneer and foremost authority on autoimmune diseases, presents a reassessment of autoimmune hepatitis, first described as “chronic active hepatitis”. He reviews the advent of autoimmune serological reactants in autoimmune hepatitis that have proven useful for diagnosis, leading to treatment with immunosuppressive agents that improved outcomes and survival. He relates the challenging efforts to define two types, i.e., one as non-organ-specific multisystem autoimmune disease (type 1) and the other uncommon (type 2) organ-specific autoimmune disease. Professor Mackay presents a scholarly assessment of the enigma posed by autoimmune hepatitis. Professor Melvin Cohn, legendary theoretical immunologist, helps us to understand the adaptive immune system by considering it as three linked modules, i.e. generation of the recognitive repertoire, sorting of the repertoire through purging anti-self, and coupling of the repertoire to appropriate effector mechanisms. He considers the decision pathways of these three components and the ways in which their protective outputs are limited. Professor D. Radford Shanklin discusses the pulmonary toxicity of oxygen with special consideration of its electronic structure and paramagnetic properties. He has long maintained an interest in oxygen uptake by the pulmonary circulation. He concludes that paramagnetic oxygen in a magnetic field influences the effect of oxygen toxicity on the lungs, yet fails to overcome significant mechanical disturbance at these strengths of field. Professor Thalachallour Mohanakumar, Dr. Nayan Sarma, senior author, and their associates provide an up-to-date account of immune response modulation by microRNAs following solid organ transplantation. In their review, they discuss the potential role of microRNAs in allograft immunity that may lead to rejection of transplanted organs concluding that they may play a significant role in allograft rejection, disease recurrence and tumor development, all of which impact patient well-being. Professor Yehuda Shoenfeld, senior author, Dr. Yinon Shipira and colleagues discovered that elevated levels of antibodies against multiple infectious agents, including Toxoplasma gondii, Epstein Barr virus, Helicobacter pylori and cytomegalovirus (CMV), may contribute to the risk of developing primary biliary cirrhosis. They observed that the association of AtxA and PBC might lead to a milder disease. Professor William Coleman and Dr Ashley Rivenbark, senior author, present a novel and innovative account of field cancerization in mammary carcinogenesis. They discuss the mechanisms that likely propel mammary carcinogenesis through field cancerization. Ductal carcinoma in situ (DCIS) may occur in an area of breast epithelium that has been altered. Results of molecular studies point to possible successive cancer-promoting genetic mutations or epimutations in the altered breast epithelium domain that leads to the development of breast cancer. In hereditary types of breast cancer, the whole breast tissue represents the altered breast epithelium domain, therefore, local DCIS resection or removal of a local invasive cancer would still leave this changed breast epithelium intact. In sporadic breast cancer, understanding the mechanisms of change in the field of breast epithelium is less clear, but deciphering the features of field cancerization in an individual case may facilitate clinical intervention. Drs. Dimiter Dimitrov, P. Ponraj, P. Parakaran and associates present an article at the frontier of HIV research based on the identification of cross-reactive IgG antibodies from an acute HIV-1 infected patient employing phage display and high-throughput sequencing.
Foreword
Using these techniques, they identified several long, highly abundant CDR3s from germline-like and somatically mutated V-genes in the VH/VL repertoires of an HIV-1 infected patient observed 40 days and then 8 months post-infection. They postulate that this may provide germline-lineage intermediates that may facilitate novel HIV-1 immunogen design. Professor Santa Ono, Dr Chuan-Hui Kuo, senior author, and colleagues investigated the role of TRB3 in mast cells sensitized with monomeric IgE. Their findings suggest that TRB3 may be a negative regulator of pro-inflammatory cytokines and chemokines determining the magnitude of the inflammatory response. Professor A. Bennett Jenson, his associates, Drs. Shin Ghim, senior author, Dr. Joh, and other colleagues report on the molecular diagnosis of laboratory mouse papillomavirus (MusPV), which describes novel methods of diagnosis and follow-up of the first known laboratory mouse papillomavirus, MusPV. Methods described in this manuscript will serve as the basis for future diagnostic assays for MusPV, which holds special significance for the Jackson Laboratory in Bar Harbor, and other providers of inbred mouse strains for research. Professor Ramesh Gupta, Dr Afsoon Moktar, senior author, and colleagues report the effect of cigarette smoking and high-risk HPV infection on the DNA integrity of vaginal cells. The single cell gel electrophoresis assay, known as the comet assay, was performed to assess, from vaginal swabs, the degree of DNA injury. They showed that the levels of DNA double-strand breaks (DSBs) are inversely correlated with both smoking and HPV status. Their results suggest that vaginal epithelium may be resistant to carcinogenic HPV infection and DNA damage associated with cigarette smoking. The absence of DNA injury in HPV positive patients may account, in part, for the relatively lower incidence of vaginal cancers compared to cervical cancers following HPV infection. This study shows that the level of DNA DSBs increases with age, which is in accord with the higher risk in older females for the accumulation of mutation and genetic instability. These findings are especially relevant in identification of the high risk population. Professor Abdolmohamad Rostami and senior author, Dr. Safavi, present an intriguing paper on the role of serine proteases in inflammation with special consideration of Bowman-Birk protease inhibitor (BBI) as a possible therapeutic mechanism for the treatment of autoimmune diseases. Serine proteases participate in various physiologic and pathologic disorders and are involved in different arms of the immune system, playing a significant role in inflammation. They have been considered as appropriate therapeutic targets for various inflammatory diseases. These authors reviewed the role of serine proteases in inflammatory diseases with emphasis on potential BBI as a novel oral therapy for multiple sclerosis. Professor Christian Koch, Dr. Eugene Melcescu and associates consider the “various faces of autoimmune endocrinopathies”, using non-tumoral hypergastrinemia in a patient with lymphocytic colitis
287
and chronic autoimmune gastritis as their model. They review the literature on the interconnected relationship between the immune and endocrine systems. The authors also provide an algorithm for patient evaluations. Professor David Kaufman and first author, Dr. Scott Schlemmer, provide a scholarly report of their elegant research on re-establishment of gap junctional intercellular communication (GJIC) between human endometrial carcinomas by prostaglandin E2. It is known that diminished intercellular communication by way of Gap junctions is linked to carcinogenesis. Gap junctional intercellular communication (GJIC) between normal human endometrial epithelial cells is facilitated by the presence in culture of endometrial stromal cells which are known to release prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) under physiological conditions. The authors discussed their research showing that PGE2 may represent an intercellular mediator between stromal and epithelial cells that controls GJIC in normal and malignant epithelial cells. They further suggest that maintenance of GJIC by preservation and replacement of PGE2 secretion by endometrial stromal cells may suppress carcinogenesis among endometrial epithelial cells. Professor Martin Zeitz, senior author Dr. Tim Meyer, and Dr. Ullrich discuss the induction of oral tolerance in humans with special emphasis on interaction of antigen with the mucosal immune system of the GI tract. They discuss models of autoimmune disease in various animals and the oral administration of autoantigens to tolerize the animal to ameliorate the disease. They examine the difficulties in attempting to repeat induction of oral tolerance in humans which would be desirable for future therapy of autoimmune diseases. Professor Annerose Berndt, Dr. Timothy Stearns, first author of the article, and their associates investigated early gene expression in inbred mouse strains susceptible to pulmonary adenoma. Their results demonstrated that expression differences between susceptible and resistant strains could be detected in young and healthy mice without manifestations of pulmonary adenomas and might provide an opportunity for early detection. The identifying genes have been reported earlier for human non-small cell cancer, suggesting the possibility of sharing between the molecular pathways of these two cancer types. It is apparent from these novel and innovative research articles, at the frontier of advances in molecular pathology, immunology and medicine, that we are poised to embark on a new and integrated approach to decode some of nature's most perplexing riddles to help us to better understand the world in which we live! Robert E. Lewis University of Mississippi Medical Center, Pathology, 2500 North State Street, Jackson 39216, United States Fax: +1 6019841835. E-mail address: [email protected].
Contents lists available at SciVerse ScienceDirect
Experimental and Molecular Pathology journal homepage: www.elsevier.com/locate/yexmp
Foreword
Foreword: Special Issue Cruse Festschrift
It is a pleasure and privilege to express genuine appreciation to the invited authors and their colleagues who have prepared the articles in this Festschrift honoring Dr. Julius Cruse. All have been associated professionally in some way or another with Dr. Cruse. Their generous decision to share premier research from their laboratories in the Festschrift attests to the high regard in which they hold the honoree. We are profoundly grateful to Elsevier Publishers for their generous support of this Festschrift for Dr. Cruse. Invited Principal Investigators and their colleagues: ▪ Professor Noel R. Rose, MD, PhD, The Johns Hopkins University, Baltimore, MD ▪ Professor Nicole Suciu-Foca, PhD, George Vlad, PhD, Columbia University College of Physicians and Surgeons, New York, NY ▪ Professor Maximilian Buja, MD, Priya Weerasinghe, MD, PhD, University of Texas Health Science Center, Houston, TX ▪ Professor Samuel French, MD, PhD, Dr. Barbara A. French, Joan Oliva, PhD, Jun Li, MD, Fawzia Bardag-Gorce, PhD, Brittany Tillman, student, Allon Canaan, MD, Harbor UCLA Medical Center, Torrance, CA ▪ Professor Olivera J. Finn, PhD, University of Pittsburgh Medical Center, Pittsburgh, PA ▪ Professor Peter Ward, MD, Drs. Markus Bosmann, Norman F. Russkamp, University of Michigan Medical Center, Ann Arbor, MI ▪ Professor Mark I. Greene, MD, PhD, FRCP, Aaron Runkle, PhD; Drs. Hongtao Zhang, Zheng Cai, Zhigiang Zhu, Barry L. Karger, Shiaw-lin Wu, Donald M. O'Rourke, Zhaocai Zhou, Qiang Wang; Drs Guoping Deng, Yan Xiao, Zhaocai Zhou, Yasuhiro Nagai, Hongtao Zhang, Bin Li, University of Pennsylvania Medical Center, Philadelphia, PA ▪ Professor Gregory Tsongalis, PhD, Cocay A. Rauwerkink, MD, Tor D. Tosteson, PhD; John M. Hill, MD, Kenneth R. Meehan, MD, PhD, Geisel School of Medicine at Dartmouth, Hartford, CT ▪ Professor Daniel S. Longnecker, MD, Michael Baker, MD, E. Scott Seeley, MD, PhD, Reetesh Pai, MD, Arief Suriawinata, MD, Mari Mino-Kenudson, MD; Giuseppe Zamboni, MD, Günter Klöppel, MD, Texas Children's Hospital, Baylor College of Medicine, Houston, TX ▪ Professor Ian Mackay 1, MD, Monash University, Victoria, Australia ▪ Professor Melvin Cohn, PhD, Salk Institute, La Jolla, CA ▪ Professor D. Radford Shanklin, MD, Marine Biological Laboratory, Woods Hole, MA ▪ Professor Thalachallour Mohanakumar, PhD, Drs. Nayan Sarma, Venkataswarup Tiriveedhi, Sabarinathan Ramachandran, Jeffrey Crippin, William Chapman, Washington University Medical Center, St. Louis, MO ▪ Professor Yehuda Shoenfeld, MD, PhD, Drs. Yinon Shapira, Nancy 1 Autoimmune Hepatitis: What Must be Said will appear in an upcoming regular issue of the journal even though it is a part of this Festschrift.
0014-4800/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yexmp.2012.10.017
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▪
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▪ ▪ ▪
Agmon-Levin, Yves Renaudineau, Bat Sheve Porat-Katz, Ori Barzilai, Maya Ram, and Pierre Youinou, Sheba Medical Center, Tel-Aviv University, Tel-Aviv, Israel Professor William Coleman, PhD, and Dr Ashley G. Rivenbach, senior author, University of North Carolina Medical Center, Chapel Hill, NC Dr. Dimiter Dimitrov, MD, PhD, Drs. Parbakaran Ponraj, Ponraj Prabakaran, Zhongyu Zhu, Yang Feng, Emily D. Streaker, National Institutes of Health, Bethesda, MD Professor Santa Ono, PhD, Drs. Chuan-Hui Kuo, Kei Morohoshi, Cho Cho Aye, Robert B. Garoon, Andrea Collins, University of Cincinnati Medical Center, Cincinnati, OH Professor A. Bennett Jenson, MD, Shin J. Ghim, PhD, Joongho Joh, PhD; Mary Proctor, DVM; Arvind Ingle, MVSc, DICVP; Kathleen A. Silva; Christopher S. Potter, PhD; John P. Sundberg, PhD, DVM; Brown Cancer Center, University of Louisville Medical Center, Louisville, KY Professor Ramesh Gupta, PhD, Drs Afsoon Moktar, senior author, Srivani Ravoori, Manicka Vachanam, Jianmin Pan, Shesh Rai, Alfred Jenson, and Lyn Parker, University of Louisville Medical Center, Louisville, KY Professor A. M. Rostami, MD, PhD, Farinaz Safavi, MD, PhD, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA Professor Christian Koch, MD, Drs. Eugen Melcescu, Reed Hogan, Keith Brown, Stewart A. Boyd, Thomas L. Abell, University of Mississippi Medical Center, Jackson, MS Professor David Kaufman, MD, PhD, Scott Schlemmer, PhD, University of North Carolina, Chapel Hill, NC Professor Dr med. habil. Martin Zeitz, Drs. Tim Meyer, Reiner Ullrich, Charité Universität, Berlin Professor Annerose Berndt, PhD, Dr. Timothy M. Stearns, Clinton L. Cario, MD, Dr. Holly S. Savage, Beverly Paigen, PhD, John P. Sundberg, DVM, PhD, University of Pittsburgh School of Medicine, Pittsburgh, PA
As Festschrift Editor, I have provided an introductory article highlighting a few details of Dr. Cruse's life and work, as medical educator, editor, author, researcher and mentor. In honoring the lifetime achievements of Julius Cruse, Professor Noel Rose, the Father of Autoimmunity, and a friend of Dr. Cruse for 54 years, relates some of his personal experiences as an eyewitness and key participant in the history of modern immunology. He presents his views of the future in areas in which Professor Cruse has made lasting contributions, i.e. the history of science and scientific communication. Professor Rose indicates that we can “chart the future best by understanding the past”. The article by Professor Nicole Suciu-Foca and senior author, Dr. George Vlad, presents an elegant investigation on the induction of
286
Foreword
antigen-specific human T supressor cells by membrane and soluble immunoglobulin-like transcript 3 (ILT3). Their findings lead them to postulate that ILT3-Fc may become a valuable new therapy for autoimmunity and transplant rejection. Dr. Priya Weerasinghe and Professor Maximilian Buja present a fascinating review on oncosis: an overlooked and important alternative mode of cell death that is different from the type of programmed cell death known as apoptosis. Whereas, apoptosis is characterized by cell shrinkage followed by disintegration, oncosis is associated with cell swelling and cytoplasmic coagulation. The authors elaborate on this novel form of in vitro and in vivo cell death and review its multiple morphologic and biochemical features. They also allude briefly to its role in disease. In their continuing investigation of aggresomes, known as MalloryDenk bodies (MDB), Professor Samuel French and his colleagues investigated whether FAT10 or IFNγ are essential for MDB formation. They fed IFNγ and FAT10 knockout mice DDC added to the control diet. They found that IFNγ KO mice, but not FAT10 KO mice, developed MDB. Thus, they demonstrated that FAT10 is requisite to induce MDB formation in DDC fed mice. Professor Olja Finn presents an elegant and insightful analysis of the host immune response to neoplasia and the advent of novel and innovative cooperative approaches by an alliance between immunologists and pathologists to apply monoclonal antibodies and immunohistochemistry to not only reach a diagnosis and prognosis but also to characterize the tumor cells and their microenvironment to gauge the host response to the neoplasm. This joint approach by immunologists and pathologists, known as “Immunoscore”, assesses the contribution of the tumor microenvironment to prognosis. It is expected to not only facilitate research in both pathology and immunology but also to benefit patients, as well. Professor Peter Ward and co-investigators, Dr. Markus Bosmann, senior author, and Dr. Norman Russkamp's in-depth studies have shed light on the pathogenesis of endotoxin-induced inflammation. Multiplexing bead-based assays were used to define responses in two murine models of in vivo challenge intraperitoneally (endotoxemia) or intratracheally (acute lung injury) with LPS. The time course of 20 inflammatory mediators in plasma or bronchoalveolar lavages was analyzed. Their results, including the current article on fingerprinting of TLR4-induced inflammatory responsiveness, have elucidated and defined the host immune response to endotoxin. Although all mediators were induced, variations in concentrations, cytokine chemokine patterns and other parameters were noted when endotoxemia and LPS-ALI were compared. Professor Mark Greene, a Senior Editor of this journal, has generously provided two research contributions from his laboratory. The first, together with senior author of the article, Dr. Aaron Runkle, and colleagues, concerns reversion of the ErbB malignant phenotype and the DNA damage response. They review contemporary understanding of ErbB signaling and DNA double strand break repair. In the second article from Professor Greene's laboratory, he and senior author of the article, Dr. Guoping Deng, and associates, discuss the role of regulatory T cells in preventing host autoimmune diseases and limiting excessive immune responses to pathogens. They elucidate the molecular and biological role of the FOXP3 N-terminal domain in immune regulation of T regulatory/supressor cells. Professor Gregory Tsongalis, Dr. Cocav Rauwerdink, senior author, and associates present a clear and informative account on the practical application of chimerism analyses in allogeneic stem cell transplant recipients and conclude that PCR-based chimerism analyses using blood provide similar information to that obtained by marrow aspirate analyses. Dr. Michael Baker, Professor Daniel Longnecker and colleagues present an instructive and enlightening review of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms of the pancreas, which have been included and intermixed in some previous
papers on pancreatic cystic neoplasms. The authors investigated whether or not the earlier concept that mucinous cystic neoplasms occasionally progress to invasive colloid carcinoma. They found no examples of colloid carcinomas associated with 291 MCN. Focal expression of CDX2, an intestinal differentiation marker, was identified in some. Their results suggest that MCN only very infrequently, if ever, invade as colloid carcinoma. These investigators conclude that most malignant mucinous cystic neoplasms invade with a tubular or ductal pattern. Professor Ian Mackay, a pioneer and foremost authority on autoimmune diseases, presents a reassessment of autoimmune hepatitis, first described as “chronic active hepatitis”. He reviews the advent of autoimmune serological reactants in autoimmune hepatitis that have proven useful for diagnosis, leading to treatment with immunosuppressive agents that improved outcomes and survival. He relates the challenging efforts to define two types, i.e., one as non-organ-specific multisystem autoimmune disease (type 1) and the other uncommon (type 2) organ-specific autoimmune disease. Professor Mackay presents a scholarly assessment of the enigma posed by autoimmune hepatitis. Professor Melvin Cohn, legendary theoretical immunologist, helps us to understand the adaptive immune system by considering it as three linked modules, i.e. generation of the recognitive repertoire, sorting of the repertoire through purging anti-self, and coupling of the repertoire to appropriate effector mechanisms. He considers the decision pathways of these three components and the ways in which their protective outputs are limited. Professor D. Radford Shanklin discusses the pulmonary toxicity of oxygen with special consideration of its electronic structure and paramagnetic properties. He has long maintained an interest in oxygen uptake by the pulmonary circulation. He concludes that paramagnetic oxygen in a magnetic field influences the effect of oxygen toxicity on the lungs, yet fails to overcome significant mechanical disturbance at these strengths of field. Professor Thalachallour Mohanakumar, Dr. Nayan Sarma, senior author, and their associates provide an up-to-date account of immune response modulation by microRNAs following solid organ transplantation. In their review, they discuss the potential role of microRNAs in allograft immunity that may lead to rejection of transplanted organs concluding that they may play a significant role in allograft rejection, disease recurrence and tumor development, all of which impact patient well-being. Professor Yehuda Shoenfeld, senior author, Dr. Yinon Shipira and colleagues discovered that elevated levels of antibodies against multiple infectious agents, including Toxoplasma gondii, Epstein Barr virus, Helicobacter pylori and cytomegalovirus (CMV), may contribute to the risk of developing primary biliary cirrhosis. They observed that the association of AtxA and PBC might lead to a milder disease. Professor William Coleman and Dr Ashley Rivenbark, senior author, present a novel and innovative account of field cancerization in mammary carcinogenesis. They discuss the mechanisms that likely propel mammary carcinogenesis through field cancerization. Ductal carcinoma in situ (DCIS) may occur in an area of breast epithelium that has been altered. Results of molecular studies point to possible successive cancer-promoting genetic mutations or epimutations in the altered breast epithelium domain that leads to the development of breast cancer. In hereditary types of breast cancer, the whole breast tissue represents the altered breast epithelium domain, therefore, local DCIS resection or removal of a local invasive cancer would still leave this changed breast epithelium intact. In sporadic breast cancer, understanding the mechanisms of change in the field of breast epithelium is less clear, but deciphering the features of field cancerization in an individual case may facilitate clinical intervention. Drs. Dimiter Dimitrov, P. Ponraj, P. Parakaran and associates present an article at the frontier of HIV research based on the identification of cross-reactive IgG antibodies from an acute HIV-1 infected patient employing phage display and high-throughput sequencing.
Foreword
Using these techniques, they identified several long, highly abundant CDR3s from germline-like and somatically mutated V-genes in the VH/VL repertoires of an HIV-1 infected patient observed 40 days and then 8 months post-infection. They postulate that this may provide germline-lineage intermediates that may facilitate novel HIV-1 immunogen design. Professor Santa Ono, Dr Chuan-Hui Kuo, senior author, and colleagues investigated the role of TRB3 in mast cells sensitized with monomeric IgE. Their findings suggest that TRB3 may be a negative regulator of pro-inflammatory cytokines and chemokines determining the magnitude of the inflammatory response. Professor A. Bennett Jenson, his associates, Drs. Shin Ghim, senior author, Dr. Joh, and other colleagues report on the molecular diagnosis of laboratory mouse papillomavirus (MusPV), which describes novel methods of diagnosis and follow-up of the first known laboratory mouse papillomavirus, MusPV. Methods described in this manuscript will serve as the basis for future diagnostic assays for MusPV, which holds special significance for the Jackson Laboratory in Bar Harbor, and other providers of inbred mouse strains for research. Professor Ramesh Gupta, Dr Afsoon Moktar, senior author, and colleagues report the effect of cigarette smoking and high-risk HPV infection on the DNA integrity of vaginal cells. The single cell gel electrophoresis assay, known as the comet assay, was performed to assess, from vaginal swabs, the degree of DNA injury. They showed that the levels of DNA double-strand breaks (DSBs) are inversely correlated with both smoking and HPV status. Their results suggest that vaginal epithelium may be resistant to carcinogenic HPV infection and DNA damage associated with cigarette smoking. The absence of DNA injury in HPV positive patients may account, in part, for the relatively lower incidence of vaginal cancers compared to cervical cancers following HPV infection. This study shows that the level of DNA DSBs increases with age, which is in accord with the higher risk in older females for the accumulation of mutation and genetic instability. These findings are especially relevant in identification of the high risk population. Professor Abdolmohamad Rostami and senior author, Dr. Safavi, present an intriguing paper on the role of serine proteases in inflammation with special consideration of Bowman-Birk protease inhibitor (BBI) as a possible therapeutic mechanism for the treatment of autoimmune diseases. Serine proteases participate in various physiologic and pathologic disorders and are involved in different arms of the immune system, playing a significant role in inflammation. They have been considered as appropriate therapeutic targets for various inflammatory diseases. These authors reviewed the role of serine proteases in inflammatory diseases with emphasis on potential BBI as a novel oral therapy for multiple sclerosis. Professor Christian Koch, Dr. Eugene Melcescu and associates consider the “various faces of autoimmune endocrinopathies”, using non-tumoral hypergastrinemia in a patient with lymphocytic colitis
287
and chronic autoimmune gastritis as their model. They review the literature on the interconnected relationship between the immune and endocrine systems. The authors also provide an algorithm for patient evaluations. Professor David Kaufman and first author, Dr. Scott Schlemmer, provide a scholarly report of their elegant research on re-establishment of gap junctional intercellular communication (GJIC) between human endometrial carcinomas by prostaglandin E2. It is known that diminished intercellular communication by way of Gap junctions is linked to carcinogenesis. Gap junctional intercellular communication (GJIC) between normal human endometrial epithelial cells is facilitated by the presence in culture of endometrial stromal cells which are known to release prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) under physiological conditions. The authors discussed their research showing that PGE2 may represent an intercellular mediator between stromal and epithelial cells that controls GJIC in normal and malignant epithelial cells. They further suggest that maintenance of GJIC by preservation and replacement of PGE2 secretion by endometrial stromal cells may suppress carcinogenesis among endometrial epithelial cells. Professor Martin Zeitz, senior author Dr. Tim Meyer, and Dr. Ullrich discuss the induction of oral tolerance in humans with special emphasis on interaction of antigen with the mucosal immune system of the GI tract. They discuss models of autoimmune disease in various animals and the oral administration of autoantigens to tolerize the animal to ameliorate the disease. They examine the difficulties in attempting to repeat induction of oral tolerance in humans which would be desirable for future therapy of autoimmune diseases. Professor Annerose Berndt, Dr. Timothy Stearns, first author of the article, and their associates investigated early gene expression in inbred mouse strains susceptible to pulmonary adenoma. Their results demonstrated that expression differences between susceptible and resistant strains could be detected in young and healthy mice without manifestations of pulmonary adenomas and might provide an opportunity for early detection. The identifying genes have been reported earlier for human non-small cell cancer, suggesting the possibility of sharing between the molecular pathways of these two cancer types. It is apparent from these novel and innovative research articles, at the frontier of advances in molecular pathology, immunology and medicine, that we are poised to embark on a new and integrated approach to decode some of nature's most perplexing riddles to help us to better understand the world in which we live! Robert E. Lewis University of Mississippi Medical Center, Pathology, 2500 North State Street, Jackson 39216, United States Fax: +1 6019841835. E-mail address: [email protected].