Biological Basis of Chemical Carcinogenesis: Insights from Benzene

Benzene is one of the best studied of the known human carcinogens. It causes leukemia in humans and a variety of solid tumors in rats and mice. Decades of research on benzene metabolism, pharmacokinetics, cytotoxicity, genotoxicity, and carcinogenicity in vivo and in vitro are starting to converge on a small set of overlapping hypotheses about the most probable biological mechanisms of benzene toxicity and carcinogenicity. Although there is still room for surprises, it seems likely that the ultimate answer to the mystery of how benzene exerts its multiple effects will consist of elaborations and extensions of one or more of the current hypotheses. This paper reviews benzene health effects and biology, showing how various aspects of metabolism and cytotoxicity fit together with genotoxic and nongenotoxic effects to help explain how benzene may cause cancer. Its goals are: (i) to introduce the qualitative biological background needed for detailed quantitative dose-response modeling of benzene cancer risks; and (ii) to survey a rapidly evolving area of research that shows promise of producing fundamental insights into the mechanisms of toxicity and carcinogenesis for several chemicals--benzene and perhaps phenols, catechols, and other hydroxylated ring hydrocarbons--in the decade ahead.     

Use of electronic media in a participant observation study

I wake up at 6:15 am, roll out of bed, and flip on my personal computer. Fieldwork is never more than a few steps away, thanks to my access to Zytek's electronic mail system. I dial into the network and spend the next 30 minutes sending out messages to set up meetings. I am planning another trip to Detroit in two weeks and send a message to the area sales manager I met last week in order to get permission to attend a two day event for a major customer. I send additional messages to set up an interview and get my name put on a distribution list, download new mail to my PC, and start printing it. After breakfast, I return to find 17 pages of mail — announcements and agendas for four meetings, a five page memo with the minutes from yesterday's pricing committee meeting, a five page memo requesting input from marketing groups for a software product, and a response from a marketing manager to my request to have lunch next Wednesday. I look through my mail for ten minutes and then head out the door. It's 7:35 am.     

Development from archaic to mature selfobject transferences

Heinz Kohut has contributed a new understanding of altered states as fixations on aspects of early developmental forms of selfobjects. Fixations can occur as a result of inadequate empathic relatedness necessary for the internalization of anxiety relieving functions. Fixations on aspects of archaic forms of the idealized selfobject may take the form of ecstatic, trance-like religious feelings. These altered states provide needed sensations that substitute for missing psychic structure. Understanding the self sustaining function that these altered states provide is crucial to the treatment. The author shares moment to moment steps in the treatment of a highly successful professional who is addicted to heightened sensation states. The development of new editions of the selfobject transferences are followed in the treatment—from primitive idealization to more mature forms of selfobject transferences.Presented at the Third National Clinical Conference of the Committee on Psychoanalysis, National Federation of Societies for Clinical Social Work.     

Business ethics and philosophical pragmatism

Today it is common for business people to refer to themselves as pragmatists. There is, however, at least one significant difference between business pragmatism and traditional philosophical pragmatism: the attitude towards ethics. In this paper we discuss several approaches business pragmatists have taken toward ethics in business. We then describe the approach taken by one philosophical pragmatist, William James. We conclude that, pragmatically speaking, philosophical pragmatism is the superior view.     

Extending the Stochastic Two-Stage Model of Carcinogenesis to Include Self-Regulation of the Nonmalignant Cell Population

One of the challenges of introducing greater biological realism into stochastic models of cancer induction is to find a way to represent the homeostatic control of the normal cell population over its own size without complicating the analysis too much to obtain useful results. Current two-stage models of carcinogenesis typically ignore homeostatic control. Instead, a deterministic growth path is specified for the population of "normal" cells, while the population of "initiated" cells is assumed to grow randomly according to a birth-death process with random immigrations from the normal population. This paper introduces a simple model of homeostatically controlled cell division for mature tissues, in which the size of the nonmalignant population remains essentially constant over time. Growth of the nonmalignant cell population (normal and initiated cells) is restricted by allowing cells to divide only to fill the "openings" left by cells that die or differentiate, thus maintaining the constant size of the nonmalignant cell population. The fundamental technical insight from this model is that random walks, rather than birth-and-death processes, are the appropriate stochastic processes for describing the kinetics of the initiated cell population. Qualitative and analytic results are presented, drawn from the mathematical theories of random walks and diffusion processes, that describe the probability of spontaneous extinction and the size distribution of surviving initiated populations when the death/differentiation rates of normal and initiated cells are known. The constraint that the nonmalignant population size must remain approximately constant leads to much simpler analytic formulas and approximations, flowing directly from random walk theory, than in previous birth-death models.(ABSTRACT TRUNCATED AT 250 WORDS)     

Employment discrimination against older workers: an experimental study of hiring practices

Pairs of resumes, one for a 57-year-old and the other for a 32-year-old, were mailed to 775 large firms and employment agencies across the United States. Although the resumes presented equal qualifications, the older job seeker received a less favorable employer response 26.5% of times when a position appeared to be vacant. Vigorous enforcement of equal opportunity laws as well as initiatives to change employer attitudes are appropriate responses to such discrimination. The technique of employment testing, demonstrated in this research, can be useful in both efforts.