This book will deal with heat shock proteins and more generally with stress-related inducible gene expression as a pleiotropic adaptive response to stress. It presents a textbook-like overview of the field not only to heat shock experts, but to physiologists, pharmacologists, physicians, neuropsychologists and others as well. It is intended to be a state-of-the-art and perspective book rather than an up-to-date presentation of recent data. It should provide a basis for new experimental approaches to fields at the edge of the classical heat shock field. Drugs, UV irradiation and environmental toxics will considered as important modulators of the stress response. Radical scavengers such as superoxide dismutases and inducible regulatory proteins of metallic ion status such as ferritin as well as immunophilins and protein disulfide isomerases will be considered within the frame of stress proteins. The potential practical applications of heat shock proteins in toxicology and medicine for the diagnosis, prognosis and eventually therapy of clinical conditions associated with an increased oxidative burden will be outlined. The role of heat shock proteins in the modulation of immune responses will also be included. The book considers heat shock from a broad perspective including fields for which heat-shock may become of importance in the very near future such as cellular responses to environmental stresses and complex stress responses under specific conditions. It was also felt timely to incorporate a whole section on medical and technological applications of stress proteins.

The thoroughly updated Eighth Edition of this classic three-volume work provides the most comprehensive, current, and authoritative information on diseases of the kidney and urinary tract. This clinically oriented reference focuses on diagnosis and treatment of specific diseases, disorders, and complications and incorporates the basic science practicing physicians need to evaluate and manage the disease process. Each of the fourteen sections is written by internationally renowned contributors and provides coverage comparable to a complete book. The first two sections review renal basic science and describe current diagnostic tools. The remaining twelve sections cover various types of diseases, including hypertension, urological problems, and urinary tract concerns. Each disease-oriented section begins with an up-to-date review of pathophysiology and then focuses on specific diseases. This edition has new lead authors for more than 25 chapters, and separate chapters on heart disease and the kidney, liver disease and the kidney, and the nephrotic syndrome.

The ability of cells to sense and respond to changes in oxygenation underlies a multitude of developmental, physiological, and pathological processes. This volume provides a comprehensive compendium of experimental approaches to the study of oxygen sensing in 48 chapters that are written by leaders in their fields.

Preconditioning to lowered oxygen levels (hypoxia) may occur when an animal is subjected to non-lethal levels of hypoxia and then returned to normoxic conditions. During a subsequent exposure to hypoxia, the pre-exposed animals may exhibit increased tolerance compared to naive animals. I have demonstrated, by analysis of critical PO2's (Pcrit), that zebrafish embryos can be preconditioned to hypoxia. Preconditioned embryos display a lower Pcrit than controls, indicating a heightened ability to endure hypoxic conditions. The role of the hypoxia inducible factor-1 (HIF-1) in promoting hypoxic preconditioning was examined. To determine the role of HIF-1 in preconditioning, embryos deficient in HIF-1alpha (using antisense oligonucleotide morpholinos) were assessed under hypoxic conditions. No significant difference between preconditioning capacities of control- and HIF-1alpha deficient embryos was observed. In addition to assessing Pcrit, a suite of hypoxia responsive genes were analysed by real time PCR. IGFBP-2 showed a significant decrease in expression in the HIF-1alpha deficient embryos, and EPO showed a significant increase in HIF-1alpha deficient embryos. All other genes examined showed no significant change between treated and control embryos.

The adaptive response to hypoxia is accompanied by widespread transcriptional changes that allow for prolonged survival in low oxygen. Many of these changes are directly regulated by the conserved hypoxia-inducible factor-1 (HIF-1) complex; however, even in its absence, many oxygen-sensitive transcripts in Caenorhabditis elegans are appropriately regulated in hypoxia. To identify mediators of these non-HIF-dependent responses, I established a hif-1 mutant reporter line that expresses GFP in hypoxia or when worms are treated with the hypoxia mimetic cobalt chloride (cobalt chloride). The reporter is selective and HIF-independent, in that it remains insensitive to a number of cellular stresses, but is unaffected by mutation of the prolyl hydroxylase egl-9, suggesting that the regulators of this response pathway are different from those controlling the HIF pathway. I used the HIF-independent reporter to screen a transcription factor RNAi library and identified genes that are required for hypoxia sensitive and cobalt chloride-induced GFP expression. Three mediators of the HIF-independent response zinc finger protein BLMP-1, chromatin remodeling factor LIN-40, and T-box transcription factor TBX-38 were isolated as mediators of the HIF-independent response. First, we show that mutation of blmp-1 renders animals sensitive to hypoxic exposure and that blmp-1 it is required for appropriate hypoxic-induced expression of HIF-independent transcripts. Further, we demonstrate that BLMP-1 is necessary for an increase of hypoxia-dependent histone acetylation within the promoter of a non-HIF-dependent hypoxia response gene. Additionally, we explore BLMP-1's role in two hypoxia-regulated physiological processes namely unfolded protein response and collagen formation. We also briefly investigate the role of LIN-40 in the hypoxia response.