Advances in Organ Biology Series

One of the mysteries of mammalian reproduction is the physiologic process that determines the length of gestation. The proper timing of birth ensures that the young individual is sufficiently developed to survive and adapt in the extrauterine environment, and that the mother is capable to provide nutrition and protection to the newborn. This volume summarizes new knowledge obtained by many researchers seeking to unravel the compile mechanisms that contribute to the maintenance and termination of pregnancy. The most important common goal of these efforts is to reduce the incidence of preterm birth, which is the leading cause of perinatal morbidity and mortality in numerous countries. Separate chapters are devoted to the best-studied animal models of parturition. In sheep, the fetus is in control of the timing of its own birth, while in avian species, oviposition is evidently determined by the female laying the feritlized egg. In humans and non-human primates, the roles of the fetus and the mother are more balanced, and involve a complicated and poorly understood interplay between the mother, the fetus, and the placenta. Some major aspects of these interactions, such as trophoblast function, myometrial contractility, and the endocrine-paracrine systems, are discussed in further chapters.

Retinoids have received considerable attention in recent years and due cognizance has been given to their versatility as biological response modifiers, as evidenced by the virtually explosive growth of literature in this field in the past few years. This volume has been designed to give a current state-of-the-art picture of retinoids. The perceived potential of retinoids in the treatment of certain disease stated has initiated attempts at identifying and synthesizing new retinoid derivatives with definable and selective effects on aberrant biological phenomena. Appropriately, therefore, we begin with the chemistry of retinoids and their derivatives together with discussions of their biological activity. Major advances have been made in understanding the mechanisms by which retinoids modulate physiological and phenotypic traits of cells. The transduction of retinoid signaling by the mediation of nuclear receptors of the steroid/thyroid receptor superfamily has now been studied extensively and the cloning and defining the characteristics of these receptors has been a focus of discussion in this volume. Retinoids also markedly modulate the transduction of extracellular signals such as those imparted by growth factors and hormones, and thus actively influence and control cellular proliferative patterns. Retinoids can alter epidermal growth factor receptor expression (Kawaguchi et al., 1994), responsiveness to thyroid hormone (Esfandiari et al., 1994; Pallet et al., 1994), inhibit the proliferative responses of hematopoietic progenitor cells to granulocyte colony stimulating factor (Smeland et al., 1994), and modulate secretion on interleukins by leukaemic cells (Balitrand et al., 1994), among other things. This has obvious implications for pharmacological manipulation of deregulated growth (Dickens and Colletta, 1993; Mulshine et al., 1993). Apoptosis is another component in the regulation of growth control. Apoptotic cell death is influenced by several agents and retinoids may function by interfering with apoptotic pathways of regulation of growth control and quite legitimately, therefore, the importance of this aspect of retinoid function has been duly recognized here.

Heart failure continues to be a major public health problem in the United States with close to half a million new cases diagnosed each year. Moreover, deaths from heart failure are on the increase, in part because of advances in the treatment of other fatal diseases, and in part from the prevalence of lifestyles indifferent to the risk factors for heart disease. This is not to say that no progress has been made in the treatment of heart failure. While for many years treatment was confined to the management of the symptoms, in recent years with the advent of ACE inhibitor and ß blacker therapies, real improvements in cardiac function and life expectancy have been achieved (Volume 4B, Leier). On a more basic level, enormous advances have been made in describing many of the changes in structure and function of the heart and the parallel neurohumoral and circulatory adaptations that occur during the onset of failure. These advances have been made not only by using various animal models of heart failure, but also using fresh failing human heart tissue, which has become readily available for experimental investigation since the advent of cardiac transplantation. Understanding the significance of many of these changes that occur during the transition to failure and the role they play in the etiology of failure is, however, a much more difficult task. These are exciting times in heart failure research. It is as though many of the pieces of the jigsaw puzzle are available but the puzzle has yet to be assembled. The objective of these volumes is to bring together some advances that have been made in recent years in defining one aspect of the failing heart, that is, the role of altered metabolism, in order to facilitate assembly of the puzzle.

Living organisms exhibit specific responses when confronted with sudden changes in their environmental conditions. The ability of the cells to acclimate to their new environment is the integral driving force for adaptive modification of the cells. Such adaptation involves a number of cellular and biochemical alteration including metabolic homeostasis and reprogramming of gene expression. Changes in metabolic pathways are generally short-lived and reversible, while the consequences of gene expression are a long-term process and may lead to permanent alternation in the pattern of adaptive responses. The heart possesses remarkable ability to adapt itself against any stressful situation by increasing resistance to the adverse consequences. Stress composes the foundation of many degenerative heart diseases including atherosclerosis, spasm, thrombosis, cardiomyopathy, and congestive heart failure. Based on the concept that excessive stress may play a crucial role in the pathogenesis of ischemic heart disease, attempts were made to design methods for preventing of myocardial injury. Creation of stress reactions by repeated ischemia and reperfusion or subjecting the hearts to heat or oxidative stress enables them to meet the future stress challenge. Repeated stress exposures adapt the heart to withstand more severe stress reactions probably by upregulating the cellular defense and direct accumulation of intracellular mediators, which presumably constitute the material basis of increased adaptation to stress. Thus, the powerful cardioprotective effect of adaptation is likely to originate at the cellular and molecular levels that compose fundamental processes in the prophylaxis of such diseases. Volume six of the Advances in Organ Biology series contains state-of-the-art reviews on myocardial preservation and cellular adaptation from the leading authorities in this subject.

These volumes differ from the current conventional texts on bone cell biology. Biology itself is advancing at breakneck speed and many presentations completely fail to present the field in a truly modern context. This text does not attempt to present detailed clinical descriptions. Rather, after discussion of basic concepts, there is a concentration on recently developed findings equally relevant to basic research and a modern understanding of metabolic bone disease. The book will afford productive new insights into the intimate inter-relation of experimental findings and clinical understanding. Modern medicine is founded in the laboratory and demands of its practitioners a broad scientific understanding: these volumes are written to exemplify this approach. This book is likely to become essential reading equally for laboratory and clinical scientists.