For many years, what has been known about recovery from addictive behaviors has come solely from treatment studies. Only recently has the study of recoveries in the absence of formal treatment or self-help groups provided an alternative source of information. This book on the process of self-change from addictive behaviors is the first of its kind, as it presents more than research findings. Rather, it presents the process of self-change from several different perspectives - environmental, cross-cultural, prevention and interventions at both societal and individual level. It provides strategies for how health care practitioners and government policy makers alike can aid and foster self-change. Directions for future research priorities are also presented.

Ideas about the nature of alcohol problems have been undergoing dramatic change over the past several years. This book summarizes the clinical research we have conducted over the past eight years; research which has evoked controversy and which, we hope, will be evaluated as having been influential in the development of a scientific approach to the clinical treatment of alcohol problems. Although we reference many studies from the general behavioral literature on alcohol problems, we make no pretense of presenting a thorough review of that literature. By and large, this book focuses on the research we have conducted, the rationale for that approach, and a detailed discussion of methods and results which cannot be presented in journal articles. The book begins by giving the reader a perspective on traditional concepts in the alcohol field, and why those concepts are now being challenged. Within that conceptual framework, we then trace the development and sophistication of our clinical research, presenting for the first time in a single work a complete consideration of the rationale, methods, and results of the study of Individualized Be havior Therapy (IBT) for alcoholics. Following a discussion of many of the more subtle aspects of that study and its results, we describe how IBT can be used in an outpatient setting-the setting in which we have conducted clinical research for the last six years.

The author is internationally renowned for his pioneering contributions to the understanding of how the anticancer agent, actinomycin D, binds to DNA and exerts its mechanism of action. Using the technique of X-ray crystallography, he and his research colleague, Shri C. Jain, solved the structure of a crystalline complex containing actinomycin and deoxyguanosine in the early 1970's, and this information led them to propose a model that is now widely accepted to understand the general features of how actinomycin binds to DNA. According to this model, the phenoxazone ring system on actinomycin intercalates between adjacent base pairs, while pentapeptide chains lie in the narrow groove of the B- helix, forming hydrogen bonds (in the case of d (pGpC) sequences) with guanine residues on opposite chains. Although X-ray crystallographic studies of actinomycin complexed to a number of different self-complementary oligonucleotides have now confirmed the overall features of this model, the precise nature of the DNA conformation remains unknown due to problems inherent in refining large structures with limited resolution data. Implicit in the original model was the assumption that actinomycin binds to B-DNA or to a distorted form of B-DNA. The possibility that actinomycin might bind to some other discretely different DNA conformational state was not envisioned at that time. Together with his research team, Dr. Sobell continued to extend his crystallographic studies to include other intercalators (these contain a diverse variety of heterocyclic ring systems) complexed to a number of different self-complementary DNA and RNA dinucleotides. The information obtained from these studies led him to propose the existence of beta-DNA, a metastable and hyperflexible DNA form, a form very different from the Watson-Crick B- and A- structures, which he believes, is intimately associated with the intercalation process. The existence of this beta-DNA structure required modification to the original actinomycin-DNA binding model. When combined with the realization that beta-DNA is an obligatory structural intermediate (i.e., transition-state intermediate) in the unwinding of duplex DNA leading to melting, this novel beta-DNA binding model leads to understanding the mechanism of action of actinomycin. This book calls attention to the wider repercussions this modified actinomycin-DNA binding model has had in understanding much of DNA physical chemistry and molecular biology. These stem from additional insights provided by another more recent area of inquiry known as Nonlinear Science.

As the DNA in our genome comprises about three billion base-pairs, with each base-pair separated by a third of a nanometer - its total length is about a meter - of all which residing within a compact form knows as chromatin. At first guess, one might think the DNA to be a wound up like a ball of yarn, but chromatin turns out to be a more complex structure, DNA being organized into hierarchical series of superhelices. Counting the right-handed double-helix as the first stage in the hierarchical ordering, the second consists of 147 base-pairs wound around the outside of nucleosomes as a left-handed toroidal-superhelix containing one and three-quarter turns. Each nucleosome contains two pairs each of four different histones, small positively charged basic proteins called H2A, H2B, H3 and H4 spatially related by two-fold symmetry. Adjacent nucleosomes remain connected together by linker DNA, additional DNA (variable in length, but generally between 5- to 60 base-pairs) that exists between nucleosomes, resulting in the formation of an extended 100 Angstrom fiber. In the presence of an additional histone (H1), DNA is known to undergo a still higher level of compaction, organizing itself into a solenoidal super helical structure having a diameter of about 300 Angstroms. This 300 Angstrom fiber can readily be seen by electron microscopy and, almost certainly, the unraveling of its structure foreshadows still further complex structural features of chromatin to be discovered in future years. In order for DNA to be organized into this hierarchical series of superhelices, there must be a source of flexibility in DNA structure that allows this to happen. Earlier, the author put forward a kinked model to understand how DNA is organized within the nucleosome. The model assumed nucleosome DNA to be in its B- form, separated by 'mixed-puckered kinks' every 10 base-pairs. Ink this book, he presents a modification to this model; this being necessary to explain important additional experimental information uncovered several years after the model was proposed. The modified model proposed that if there were an equal probability of both 10 base-pars of B- DNA or 11 base-pairs of A- DNA existing within any given segment of the left-handed toroidal super helical structure - these being connected together by 'mixed-puckered kinks' - then a population of such aperiodic structures can be expected to give rise to the periodic cutting-patterns observed experimentally. This would be true for naked DNA molecules immobilized on a calcium-phosphate crystalline surface as well, provided they also formed left-handed toroidal superhelices under these conditions. In both cases, probability considerations predict cutting patters to be symmetrically distributed around integral multiples of 10.5 base-pairs along DNA, the relative magnitudes of the surroundings peaks in these patterns being governed by the binomial distribution - the proof of which is presented in this book.