Modern cell biology has brought improvements in therapy for advanced malignant diseases through immunomodulation, hematopoietic stem cell transplantation, and other advanced techniques. Collected here are selected papers from the Fifth International Symposium of Keio University for Life Sciences and Medicine on Cell Therapy.
All chapters include innovative basic research for clinical application: immunotherapy, cancer vaccination, molecular biology of hematopoietic stem cells, stem cell processing, and gene therapy.
The book is divided into three parts: Immunotherapy for malignant diseases; Hematopoietic stem cell biology and clinical application; and International collaboration in hematopoietic stem cell transplantation. Included in the third part is information on bone marrow registries from around the world.
The book thus presents up-to-date information on biological and clinical aspects of treatment, with insight into the future of cell therapy.

Computers have revolutionized the analysis of sequencing data. It is unlikely that any sequencing projects have been performed in the last few years without the aid of computers. Recently their role has taken a further major step forward. Computers have become smaller and more powerful and the software has become simpler to use as it has grown in sophistication. This book reflects that change since the majority of packages described here are designed to be used on desktop computers. Computer software is now available that can run gels, collect data, and assess its accuracy. It can assemble, align, or compare multiple fragments, perform restriction analyses, identify coding regions and specific motifs, and even design the primers needed to extend the sequencing. Much of this soft ware may now be used on relatively inexpensive computers. It is now possible to progress from isolate d DNA to database submission without writing a single base down. To reflect this progression, the chapters in our Sequence Data Analysis Guidebook are arranged, not by software package, but by fimction. The early chapters deal with examining the data produced by modem automated sequenc ers, assessing its quality, and removing extraneous data. The following chap ters describe the process of aligning multiple sequences in order to assemble overlapping fragments into sequence contigs to compare similar sequences from different sources. Subsequent chapters describe procedures for compar ing the newly derived sequence to the massive amounts of information in the sequence databases."

During the last decade, an increased interest in somatic stem cells has led to a flurry of research on one of the most accessible tissues of the body: skin. Much effort has focused on such topics as understanding the heterogeneity of stem cell pools within the epidermis and dermis, and their comparative utility in regenerative medicine applications. In Skin Stem Cells: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study skin stem cells. These include methods and techniques for the isolation, maintenance and characterization of stem cell populations from skin. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Skin Stem Cells: Methods and Protocols seeks to aid scientists in the further understanding of these diverse cell types and the translation of their biological potential to the in vivo setting.

This volume is a collection of chapters contributed by leading experts in the emerging field of analytical morphology. Its contents cover a wide range of techniques for morphologic research and diagnosis and it is intended for anyone who wants to keep abreast of the rapid development in this field. Analytical morphology is a contemporary science dealing with the analy- sis of shape, size and color arrangement of cell and tissue components by means of a variety of analytical maneuvers. It differs from conventional mor- phology and histopathology in that it employs methods beyond routine hema- toxylin and eosin or histochemical staining. To a great extent, the advance- ment of analytical morphology is based on new advances in other disciplines, such as immunology, molecular biology, laser technology, microwave tech- nology and computer science. Using these new methods, particular cellular components that would otherwise remain invisible, such as peptides, pro- teins, or nucleotide sequences, are highlighted by visible markers through chemical, physical, immunological or molecular biological reactions. These methods include immunocytochemistry, in situ hybridization, in situ poly- merase chain reaction, antigen retrieval, image analysis, and the like. Analytical morphology is the foundation of contemporary medicine. It provides concrete and visible evidence for many conceptual deductions of other life science disciplines.

Myc controls multiple cellular functions, including cell proliferation, growth, differentiation and death, both directly and indirectly, through its modulation of downstream transcriptional programs. In The Myc Gene: Methods and Protocols, experts in the field summarize the standard and novel techniques that allow the studying of Myc mechanism of action in normal and cancer cells, in vitro and in vivo, in one succinct manual. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.

The discovery of adult neurogenesis caused a paradigm shift in the neurosciences. For more than 100 years, it was believed that adult neurons do not regenerate. Joseph Altman and Fernando Nottebohm found proof to the contrary and changed the course of history. Their research, included here, provides the foundations of the field. Today, adult neurogenesis is a rapidly expanding discipline applicable to the study of brain development and diseases, learning and memory, aging, and neuropsychiatric disorders. With multiple authors, the 27 chapters of this book contain the latest work in two volumes. The first presents the basic biology of adult neurogenesis in non-mammalian vertebrates and in the mammalian hippocampus and olfactory bulb, and the second discusses clinical implications and delves into adult neurogenesis and brain injury as well as neurodegenerative and neuropsychiatric pathologies. With details of the anatomy, physiology, and molecular biology of the two neurogenic brain regions, this book provides indispensable knowledge for many areas of neuroscience and for experimental and clinical applications of adult neurogenesis to brain therapy.

Studies related to recombinant gene expression have brought new advance such as the emergence of the "omics" technologies. While Escherichia coli, Sacharomyces cerevisiae and insect cells continue to be the dominant production platforms of recombinant proteins. In Recombinant Gene Expression: Review and Protocols, Third Edition, expert researchers in the field detail many of the methods now commonly used to study recombinant gene expression. These include methods and techniques for bacteria, lower eukaryotes, fungi, plants and plant cells, and animals and animal cells. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Recombinant Gene Expression: Review and Protocols, Third Edition seeks to aid scientists in the further study of this crucially important research into recombinant gene expression.

Award-winning researchers review of key aspects of DNA repair in a wide variety of organisms, including all-important model systems. The book focuses on DNA damage and repair in prokaryotic and model eukaryotic systems, emphasizing the significant progress that has been made in the past five years. Each chapter has undergone a rigorous peer-review cycle to ensure definitive and comprehensive treatment. Major topics include UV and X-Ray repair, repair of chemical damage, recombinational repair, mismatch repair, transcription-repair coupling, and the role of DNA repair in cell cycle regulation.

Initially believed to be inactive molecules, glycans are now considered essential for life, both under normal and pathological conditions.

This volume of the series "Biology of Extracellular Matrix " reviews the most recent findings on the role of glycans in the development of diseases and the possible therapeutic use of this class of molecules. It shows how the interaction of glycans with growth factors, growth factor binding proteins, extracellular proteases, protease inhibitors, chemokines, morphogens, and adhesive proteins regulates inflammation, infection, cancer, atherosclerosis, thrombosis and embryonic stem cell biology. Furthermore, an extensive survey about the structure and pharmacological effects of unique marine glycosaminoglycans is discussed as well as the possibility of using these glycans as therapeutic agents.

Recently, important new findings in the polyamine field and a variety of new experimental systems have revolutionized the study of these ubiquitous cellular components, essential for normal growth and development. In "Polyamines: Methods and Protocols," leading researchers contribute an extensive collection of up-to-date laboratory techniques for the further pursuit of polyamine study. The volume delves into vital subjects such as neoplasia studies with animal models and human patients, therapeutic roles for polyamine inhibitors and analogs, polyamine metabolism and oxidative damage, polyamines as regulators of critical ion channels, as well as polyamine transport systems and polyamine-responsive genes. Written in the highly successful "Methods in Molecular Biology " series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and expert notes on troubleshooting and avoiding known pitfalls.

Comprehensive and cutting-edge, "Polyamines: Methods and Protocols" provides a key resource for all scientists pursuing the study of this dynamic and significant aspect of cellular biology."

The Tohoku University Graduate School of Dentistry first introduced the concept of "Interface Oral Health Science", designed to establish and maintain healthy oral cavities, which are home to a number of mixed systems. Included in those systems are: (1) host tissues such as teeth, mucosa, muscle and bone, (2) parasites and microorganisms cohabiting the surfaces of the oral cavity and (3) biomaterials that are used for the rehabilitation of oral functions. In addition, (4) these systems are subject to severe and complex mechanical forces. Therefore, it is critical to promote dental studies that integrate a wide range of interdisciplinary research as medicine, agriculture, material science, engineering, and pharmacology. With this incentive, international symposiums for interface oral health science have been held several times in the past. The concept has since refined and expanded, the result being the "Biosis-Abiosis Intelligent Interface," and projects aiming at the creation of highly functional and autonomic intelligent interfaces are ongoing. This book brings together a number of studies on incentives and projects by leading authors. Topics include biosis-abiosis interface of dental implants, biomaterials in interface science, biomedical engineering interface and cell manipulation and tissue regeneration. Readers not only from the field of dentistry but also many related areas will find this book a valuable resource.

Protein glycosylation is now acknowledged as a major posttranslational modification with significant effects on protein folding, conformation distri- bution, stability, and activity. The added oligosaccharide chains are large and diverse and have specific recognition motifs important in many aspects of cell interactions and regulation. As such, there is a growing need to communicate the analytical methods of the specialist carbohydrate chemist, biochemist, and physicochemist to protein experts and the pharmaceutical industry. Other areas that come under the influence of the glycosciences are DNA interactions with ubiquitous saccharide-containing antibiotics and antitumor drugs; inhibitors of viral infection; bacterial, mycobacterial, and parasite antigens; glycolipids; glycophosphatidylinositol protein membrane anchors; and (glyco)protein- proteoglycan interactions. Compared to the first edition of this book, Glycopro- tein Analysis in Biomedicine, less emphasis is given to biomedical aspects, but these chapters are still pertinent today. The significant differences in the con- tent relate to advances in analysis relevant to biotechnology; for example, the production of recombinant glycoproteins and other therapeutics. It must also not be forgotten that the methods here described in Glycoanalysis Protocols are relevant to exploiting the commercial potential of carbohydrates in fields related to agriculture, food, and the domestic and chemical industries. The emphasis of the book remains in bringing the glycosciences into mainstream biochemistry. The analytical methods covered in Glycoanalysis Protocols are the re- sult of experts translating their life's works into easy-to-follow recipes.

The concept of hormonal regulation using intercellular peptide messengers dates back to the discovery of secretin in 1902. The concept was simple: A peptide is released from specific hormone producing cells, endocrine cells, into circulation upon stimulation of the cells. The peptide hormone travels via blood to its target, the cells of which are equipped with specific receptors for high-affinity binding of the particular peptide hormone. Receptor binding subsequently elicits action of the target cells. This concept has been seriously challenged by modern biochemistry and cell biology. Thus, it is now well established that the gene of a specific peptide hormone may be expressed in different types of endocrine cells, in neurons, and in some instances also in adipocytes, myocytes, osteoblasts, and immune cells. Today, only a few hormones - including the old master hormone insulin - represent the original endocrine paradigm. Instead, the widespread cellular synthesis now raises the qu- tion of how the body maintains the regulation of its functions by peptide hormones when a hormone may originate from a variety of cells.

Comprehensive up-to-date treatment of molecular bioenergetic mechanisms Authors are the inventors of this branch within modern biology Written also for advanced undergraduate and graduate students in biophysics, biology and medicinal chemistry Principles of Bioenergetics summarizes one of the quickly growing branches of modern biochemistry. Bioenergetics concerns energy transductions occurring in living systems and this book pays special attention to molecular mechanisms of these processes. The main subject of the book is the "energy coupling membrane" which refers to inner membranes of intracellular organelles, for example, mitochondria and chloroplasts. Cellular cytoplasmic membranes where respiratory and photosynthetic energy transducers, as well as ion- transporting ATP-synthases (ATPases) are also part of this membrane. Significant attention is paid to the alternative function of mitochondria as generators of reactive oxygen species (ROS) that mediate programmed death of cells (apoptosis and necrosis) and organisms (phenoptosis). The latter process is considered as a key mechanism of aging which may be suppressed by mitochondria-targeted antioxidants.

Extracellular purines and pyrimidines (ATP, ADP, UTP and adenosine) are released into the extracellular milieu in response to a variety of stress conditions and act as important regulators of vascular homeostasis. This new book is uniquely focused on the signaling actions of extracellular purines in endothelial cells and the crucial role of extracellular purines in regulation of angiogenesis, vascular tone, cell permeability, wound healing, inflammation and cell-to-cell communication. This book examines the responses of endothelial cells, originating from various tissues (such as cornea, pancreas and uterus), to extracellular nucleotides and adenosine under physiological and pathological conditions, i.e. pregnancy, hypoxia, hypertension, inflammation and diabetes. In the book's 12 chapters, the role of purinergic signaling in endothelium-dependent tissue perfusion, regulation of endothelial barrier function, and angiogenesis are discussed. The mechanisms of ATP release and its role in intercellular communication are also presented. In addition, the book provides the most up to date mechanisms of extracellular nucleotide metabolism by purine-converting ecto-enzymes and their contribution to purinergic signaling in endothelial cells originating from various vascular beds. This book is a valuable resource for biomedical research scientists, clinical scientists, graduate students and health science professionals interested in the mechanisms of extracellular purine function in endothelial cells under physiologic and pathologic conditions.

In 1976 I wrote a monograph on lysosomes (Lysosomes: A Survey, Springer Verlag, Vienna) that was intended as an up-to-date, comprehensive survey. Whatever success I may have achieved then in fulfilling that intention, even the effort now would be foolhardy. The literature has grown so rapidly in the past decade that I certainly could not even read all of the essential papers, let alone understand and analyze them. My goal here, therefore, is simply to introduce the major features of lysosomes at a level I hope will be useful both to I;ldvanced students and to researchers interested in obtaining a broad background. This is in keeping with the design of the Cellular Organelles series: the series is more a set of advanced texts than of review monographs. This design carries with it the decision not to support each point by refer ences to the original literature. I apologize for the injustice involved in such a decision but feel that in any event it would be impossibly unwieldy to cite, adequately and in a balanced manner, the contributions of the vast network of researchers responsible for the information upon which I draw."

This volume contains protocols specifically designed for studying cell signaling mediated by ErbB receptors, all applicable to the study of a broad range of ErbB receptor-mediated signaling from basic research to clinic applications, from cultured cells to various animal models and primary cancer cells from patients. After some overviews, the book continues by covering common protocols for studying various aspects of ErbB receptor-mediated cell signaling, newly-developed methods in biomedical research that are also widely-used in the study of ErbB receptor signaling, epidermal growth factor receptor (EGFR) signaling in Drosophila, as well as protocols for studying ErbB receptor signaling in various animal model systems. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Detailed and easy-to-follow, ErbB Receptor Signaling: Methods and Protocols serves as an ideal guide for researchers who are studying the cell signaling mediated by ErbB receptors and other receptor tyrosine kinases.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Plants produce more than 30,000 types of chemicals, including pharmaceuticals, pigments and other fine chemicals, which is four times more than those obtain ed from microbes. Plant cell culture has been receiving great attention as an alternative for the production of valuable plant derived secondary metabolites, since it has many advantages over whole plant cultivation. However, much more research is required to enhance the culture productivity and reduce the pro cessing costs, which is the key to the commercialization of plant cell culture pro cesses. The recent achievements in related biochemical engineering studies are reviewed in Chapter 1. The effect of gaseous compounds on plant cell behavior has been little studied, and Chapter 2 focuses on these gas concentration effects (including oxygen, carbon dioxide, ethylene and others, such as volatile hor mones like methyl jasmonate) on secondary metabolite production by plant cell cultures. Two metabolites of current interest, i. e. , the antimalarial artemisinin (known as "qing hao su" in China) that is produced by Artemisia annua (sweet wormwood) and taxanes used for anticancer therapy that are produced by species of Taxus, are taken as examples. Bioprocess integration is another hot topic in plant cell culture technology. Because most of the plant secondary meta bolites are toxic to the cells at high concentrations during the culture, removal of the product in situ during the culture can lead to the enhanced productivity. Various integrated bioprocessing techniques are discussed in Chapter 3.

Transcriptome Profiling: Progress and Prospects assists readers in assessing and interpreting a large number of genes, up to and including an entire genome. It provides key insights into the latest tools and techniques used in transcriptomics and its relevant topics which can reveal a global snapshot of the complete RNA component of a cell at a given time. This snapshot, in turn, enables the distinction between different cell types, different disease states, and different time points during development. Transcriptome analysis has been a key area of biological inquiry for decades. The next-generation sequencing technologies have revolutionized transcriptomics by providing opportunities for multidimensional examinations of cellular transcriptomes in which high-throughput expression data are obtained at a single-base resolution. Transcriptome analysis has evolved from the detection of single RNA molecules to large-scale gene expression profiling and genome annotation initiatives. Written by a team of global experts, key topics in Transcriptome Profiling include transcriptome characterization, expression analysis of transcripts, transcriptome and gene regulation, transcriptome profiling and human health, medicinal plants transcriptomics, transcriptomics and genetic engineering, transcriptomics in agriculture, and phylotranscriptomics.

The Hippo signaling pathway is rapidly gaining recognition as an important player in organ size control and tumorigenesis, and many leading scientists are showing increased interest in this growing field and it's relation to cancer. The chapters in this volume cover virtually all aspects of tumor biology, because members of the Hippo Pathway have been associated with numerous well-established cell signaling pathways, just to name a few; Ras, Wnt, TGFbeta and p53. Moreover, Hippo signaling is not solely involved in regulating "classic" tumor characteristics such as cell proliferation, survival and growth, but is also diversely involved in cell-autonomous and non-cell-autonomous differentiation, migration and organ size control. The primary audience are researchers interested in basic science in the areas of tumor suppression, cell cycle and size regulation, development and differentiation.

Cell growth, one of the most fundamental of biological processes, has long been among the least understood. On April 24-28, 1984 sci- entists convened from around the world in Canada's Banff National Park for The International Cell Cycle Society's 10th Conference. Their purpose was to evaluate recent developments in the field of cell prolif- eration and to explore the interrelationship between cell growth, de- velopment, and differentiation, and proliferative diseases such as can- cer. Growth, Cancer, and the Cell Cycle collects those conference papers that present the most recent advances in this field. The first section of the book is Gene Expression and Development During Growth. It examines the structure and function of chromatin, DNA unwinding proteins, and nonhistone nuclear proteins, then ex- plores transcriptional, translational, and post-translational regulation during the cell cycle and the interrelationship and coordinate regula- tion of cell growth, differentiation, and gene expression. The second section, Growth Activation and Dormancy, focuses upon the events that occur during the transition between active cell growth and proliferative quiescence. The role of DNA strand breaks, protein kinase activity, growth regulatory factors, and the cytoskeleton are examined. Section three discusses The Topology of the Cell Cycle. It reviews genetic approaches for determining the sequence of events and cau- sality relationships that comprise and coordinate the many separate processes involved in cell cycle progression and describes the use of multipara meter flow cytometry to characterize the mammalian cell cy- cle and intracellular metabolic and transitional growth states.

In Epiblast Stem Cells: Methods and Protocols, expect researchers in the field provide a detailed collection of techniques and protocols useful to the study of the biology of the pluripotent epiblast. These include methods and techniques used to study epiblast development in different amniotes. This collection brings together contributions from the fields of embryology, stem cell biology and developmental biology together, providing a single volume with detailed procedures for the isolation and culture of epiblasts at different stages of development, and techniques for the study of differentiation into specific lineages. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, a complete list of the necessary materials and reagents, detailed laboratory protocols, and extensive notes providing suggestions on troubleshooting and how to overcome common difficulties. Comprehensive and cutting-edge, Epiblast Stem Cells: Methods and Protocols serves as a resource to individuals interested in studying the biology of pluripotent cells.

Animal cell technology is a growing discipline of cell biology which aims not only to understand structures, functions and behaviors of differentiated animal cells but also to ascertain their abilities to be used for industrial and medical purposes. The goal of animal cell technology includes accomplishments of clonal expansion of differentiated cells with useful ability, optimization of their culture conditions, modulation of their ability for production of medically and pharmaceutically important proteins, and the application of animal cells to gene therapy and artificial organs. This Volume gives the readers a complete review of the present state of the art in Japan. The Proceedings will be useful for cell biologists, biochemists, molecular biologists, immunologists, biochemical engineers and other disciplines related to animal cell culture, working either in academic environments or in industries of biotechnology and pharmacy.

Historically, the major emphasis on the study of purinergic systems has been predominantly in the areas of physiology and gross pharmacology. The last decade has seen an exponential in- crease in the number of publications related to the role of both adenosine and A TP in mammalian tissue function, a level of interest that has evolved from a more molecular focus on the identity of adenosine and A TP receptor subtypes and the search for selective ligands and development of radioligand binding assays by Fred Bruns and colleagues (especially that for A receptors) that played z a highly significant role in advancing research in the area. In the 60 years since adenosine was first shown to be a potent hypotensive agent, a considerable investment has been made by several pharmaceutical companies-including Abbott, Byk Gulden, Takeda, Warner-LambertlParke Davis, Boehringer Mann- heim, Boehringer Ingelheim, Nelson/Whitby Research and CffiA- Geigy-as well as John Daly's laboratory at the National Institutes of Health, to design new adenosine receptor ligands, and both agon- ists and antagonists with the aim of developing new therapeutic entiities. Numerous research tools have derived from these efforts including: 2-chloroadenosine, R-PIA (~-phenylisopropyladeno- sine; NECA (5' N-ethylcarboxamidoadenosine); CV1808; CI936; PD 125,944; ~-benzyladenosine; PACPX; CPX; CPT; XAC; CGS 15943 and CGS 21680. Yet in the realm of therapeutics it was only in 1989 that adenosine itself was approved for human use in the treatment of supraventricular arrythmias.