Bacteria and plants produce powerful toxins that can cause a variety of diseases, some of which are lethal for many animal species. The mechanisms of action are common to many of these toxins and represent general pathways for the interaction of a number of biomolecules with target cells, such as binding to specific surface receptors, internalizati

Presenting all preclinical and clinical information available on genetically engineered toxins, this unique, single-source reference provides the most up-to-date methods and practical examples for conducting clinical studies in toxin molecular biology.;Reviewing difficult problems and their solutions, Genetically Engineered Toxins discusses techniques for clo;ning, expressing, and purifying recombinant toxins and genetically modified recombinant toxins; documents structure-function relationships in toxins, including comparative information; supplies theory and illustrations of chimeric toxins; delineates the preclinical assessments of new reagents; and summarizes approaches to drug design.;With over 1100 literature citations, Genetically Engineered Toxins is an invaluable resource for biochemists, molecular biologists, biotechnologists, pharmacologists, toxicologists, X-ray crystallographers, enzymologists, oncologists, hematologists, immunologists, rheumatologists, botanists, and graduate-level students in molecular biology, biotechnology, and clinical oncology courses.

The driving force for research on cytokines has always been their clinical promise. Their biological properties suggested a key role in hematopoiesis, immunity, tumor genesis, hemostasis, vascularization, repair of connective tissues and integration of the immune system with the neuroendocrine system. Animal studies have shown that cytokines could be used as effective biotherapeutics with easily manageable and reversible toxicities. Clinical trials have confirmed these findings, culminating in the licensing of a number of the cytokines such as interferon alpha, interferon gamma, interleukin 2, erythropoietin, granulocyte colony stimulating factor, and granulocyte-macrophage colony stimulating factor. Many other cytokines are in clinical trials. This is the first comprehensive volume on the cytokines written primarily from a medical perspective. After presenting background information about the structure, production, assays and systemic effects of cytokines and their receptors, it is organized around diseases and organ systems. Infectious diseases, autoimmunity, immunodeficiency states, defective hematopoiesis, allergies, injury repair, cancer, vascular and skin diseases, and neurological disorders are all covered. This work reviews the role that cytokines play in the pathogenesis, diagnosis and therapy of each disease. The authors assess both the current state of the art and the potential for future applications.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good indepth reviews of cancer topics, and published symposium lectures are often the best overviews available. Un fortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up-to-date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc. Second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more.

This is a survey of well characterized and recently discovered bacterial protein toxins. Leading investigators of the respective toxins review the various molecular mechanisms of action, ranging from toxin-induced ADP-ribosylation up to membrane perforation by pore-forming toxins. Thy also describe the consequences on host physiology before focusing on potential applications as cell biological and pharmacological tools for research and medical applications. Detailed descriptions of the methodology include the engineering and use of modified and chimeric toxins for better performance. A solid introduction to toxin structure and functions, as well as a valuable source of methodology for researchers in molecular biology, pharmacology and experimental medicine.

The plant toxin ricin is one of the most potent and lethal substances known. Due to its wide availability and the ease of production, ricin has been exploited as an agent of bioterrorism and biological warfare and is classified as a level B threat. Tons of ricin are produced annually worldwide as a by-product of castor oil, leading to exposure. Currently, there is no proven safe treatment for ricin intoxication. Ricin consists of an active A subunit (RTA) covalently linked to a cell binding B subunit (RTB). RTA depurinates a universally conserved adenine in the sarcin–ricin loop (SRL) of the large rRNA and inhibits protein synthesis. RTA-antibody complexes have been explored as immunotoxins against cancer cells. The articles published in this book address the history of ricin research, how ricin enters cells and traffics to the ribosome, how it inactivates ribosomes, how it induces inflammatory signaling pathways and programmed cell death, the design of therapies against ricin intoxication, and innovative assays for ricin detection.

Receptor-Mediated Binding and Internalization of Toxins and Hormones presents the proceedings of a conference conducted for the purpose of exploring relationships between hormones and toxins, specifically, receptor-mediated internalization of toxins and hormones and the role of this internalization in message transmission and biodegradatory processes. This book is divided into three sections, with the first focusing on model systems of internalization. It presents pictorial illustrations of the receptor-mediated endocytosis of low-density lipoprotein via coated regions of membrane and discusses the receptor for lysosomal enzymes on the surface of cultured fibroblasts. The second section focuses on toxins and hormones and discusses such topics as receptor-mediated internalization of diphtheria toxin, diphtheria toxin interactions with an inhibitory activity from plasma membranes, and uptake mechanisms for ADP-ribosylating toxins. The third and final section focuses on hybrids and discusses such topics as chimeric toxins containing fragment A from diphtheria toxin, directed entry of hybrid proteins into cells via alternate receptors, and a hybrid protein of monoclonal anti-THY 1.2 and diphtheria toxin fragment A. This book will be of interest to practitioners in the fields of endocrinology, cell biology, and molecular genetics.

This book describes the major achievements and discoveries relevant to bacterial protein toxins since the turn of the new century illustrated by the discovery of more than fifty novel toxins (many of them identified through genome screening). The establishment of the three-dimensional crystal structure of more than 20 toxins during the same period offers deeper knowledge of structure-activity relationships and provides a framework to understand how toxins recognize receptors, penetrate membranes and interact with and modify intracellular substrates. - Edited by two of the most highly regarded experts in the field from the Institut Pasteur, France - 14 brand new chapters dedicated to coverage of historical and general aspects of toxinology - Includes the major toxins of both basic and clinical interest are described in depth - Details applied aspects of toxins such as therapy, vaccinology, and toolkits in cell biology - Evolutionary and functional aspects of bacterial toxins evaluated and summarized - Toxin applications in cell biology presented - Therapy (cancer therapy, dystonias) discussed - Vaccines (native and genetically engineered vaccines) featured - Toxins discussed as biological weapons, comprising chapters on anthrax, diphtheria, ricin etc.

International Review of Neurobiology