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Blood'Brain Barrier
Blood–brain barrier (BBB) breakdown leading to cerebral edema occurs in many brain diseases—such as trauma, stroke, inflammation, infection, and tumors—and is an important factor in the mortality arising from these con- tions. Despite the importance of the BBB in the pathogenesis of these diseases, the molecular mechanisms occurring at the BBB are not completely und- stood. In the last decade a number of molecules have been identified not only in endothelial cells, but also in astrocytes, pericytes, and the perivascular cells that interact with endothelium to maintain cerebral homeostasis. However, the precise cellular interactions at a molecular level in steady states and d- eases hav...
Hypertension
A collection of new and essential molecular techniques for cardiovascular research. These readily reproducible methods range widely from producing congenic, consomic, transgenic, and knockout models of hypertension to the gene transfer of specific genetic material using nonviral (polymers, liposomes, and antisense agents) and adenoviral vectors. Additional techniques described include single nucleotide polymorphism (SNP) genotyping, RNA interference, microarray analysis, pharmacogenetics, and pharmacogenomics for the genetic dissection of hypertension, as well as a practical method for deriving cardiomyocytes from embryonic stem cells that would serve as replacement cells for those damaged by hypertension or heart attack. The book offers both novice and experienced hypertension researchers an indispensable collection of readily reproducible techniques for successful research, work that has already dramatically improved the outlook for hypertensive patients, and promises much future success.
Renal Disease
“Rule IV. There is need of a method for finding out the truth. Rule V. Method consists entirely in the order and disposition of the objects toward which our mental vision must be directed if we would find out any truth. We shall comply with it exactly if we reduce involved and obscure propositions step be step to those that are s- pler, and then starting with the intuitive apprehension of all those that are absolutely simple, attempt to ascend to the knowledge of all others by precisely similar steps. ” —Rene Descartes, Rules for the Direction of Mind “...Perhaps he would sooner satisfy himself by resolving light into colours as far as may be done by Art, and then by examining the properties of those colours apart, and afterwards by trying the effects of reconjoyning two or more or all of those, and lastly by separating them again to examine what changes that reconjunction had wrought in them. This will prove a tedious and difficult task to do it as it ought to be done but I could not be satisfied till I had gone through it. ” —From Newton’s letter, quoted in The Life of Isaac Newton by Richard Westfall. Cambridge University Press, 1993.
Molecular Cardiology
The aim of Molecular Cardiology: Methods and Protocols is to document state-of-the-art molecular and genetic techniques in the area of cardiology. These modern approaches enable researchers to readily study heart diseases at the molecular level and will promote the development of new therapeutic str- egies. Methods for genetic dissection, signal transduction, and microarray analysis are excellent tools for the study of the molecular mechanisms of cardiovascular diseases. Protocols for transgenesis take advantage of recent advances in many areas of molecular and cell biology. Transgenic models of heart diseases (cardiac hypertrophy, cardiac dysfunction, and so on. ) are powerful tools for the...
Hepatitis B and D Protocols
Despite the availability of an effective vaccine, there are still 400 million people, worldwide who are chronically infected with hepatitis B virus (HBV). For them, the vaccine, as currently applied, has no value. Given the possible consequences of HBV infection, the number of those chronically infected with HBV presents an enormous public health challenge. For example, the major etiology of hepatocellular carcinoma (HCC) is chronic infection with HBV. Although fifth in cancer incidence, worldwide, HCC/liver cancer is the third leading cause of cancer death. The high mortality as- ciated with HCC arises because the disease is often detected late and is unresponsive to treatment. The number o...
Novel Anticancer Drug Protocols
We are in an exciting era in the war against cancer, with real prospects for novel anticancer drugs that are cancer cell-specific without the toxicities that have been the hallmark of conventional cytotoxic cancer chemotherapy. Advances in cancer cell biology fueled by the molecular biology revolution have resulted in the uncovering of many novel potential molecular targets for cancer therapy. New anticancer drug discovery and development is now largely focused on exploiting these new molecular targets, which encompass oncogenes, tumor s- pressor genes, and their gene products, as well as targets involved in tumor angiogenesis, metastasis, survival, and longevity mechanisms. Exploitation of some of these targets has already yielded fruits and introduced new paradigms of molecularly targeted cancer therapy into the clinic, namely, protein kinase in- bition by antibodies or small molecules, exemplified by Herceptin® (trastuzumab), a humanized antibody targeted against the HER-2 growth factor receptor tyrosine kinase for the treatment of metastatic breast cancer; and Gleevec, a small molecule bcr-abl kinase inhibitor for the treatment of chronic myel- enous leukemia.
Chemosensitivity
A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity,Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains cutting-edge protocols for classifying tumors into response categories and for customizing therapy to individuals. These readily reproducible techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor.
Tumor Necrosis Factor
Because tumor necrosis factor-a (TNF-a) plays a pivotal role in the regulation of homeostasis and inflammatory immune responses, it offers valuable research opportunities to develop new drugs for the treatment of a wide range of disorders, including cancer, septic shock, rheumatoid arthritis, and other inflammatory diseases. In Tumor Necrosis Factor: Methods and Protocols, well-versed experimentalists survey the basic and translational research being conducted in this field and describe in detail the methods they have developed for TNF production, characterization, mutagenesis, and detection in biological specimens. They also provide several in vitro assays and animal models for studying the...
Frontiers in Cerebral Vascular Biology
During the past three decades, the cerebral vasculature and its role in blood-brain transport has been an increasingly active area of investigation and learning, particularly from an anatomical and physiological point of view. However, much less is known at the molecular and cellular level about the blood-brain barrier especially regarding the macromolecules responsible for transport, the roles played by vascular wall components (endothelial cell, pericyte, smooth muscle, basement membrane), and the mechanisms regulating brain vascular-specific protein expression and their molecular alterations during development and disease. Fundamental questions still unanswered include: What are the molec...
Vaccine Protocols
Vaccine research and development is advancing at an unprecedented pace, with an increasing emphasis on rational design based upon a fundamental und- standing of the underlying molecular mechanisms. The aim of this volume is to provide a selection of contemporary protocols that will be useful to both novice and advanced practitioner alike. The variety of procedures required to design, develop, produce, and assess a vaccine is immense and covers aspects of ch- istry, biochemistry, molecular biology, cell biology, and immunology. No single volume can hope to cover these topics exclusively. Rather, here we attempt to provide a methods sourcebook focusing on hands-on practical advice. Comp- menta...
