Death conceptualization

The concept of biomarkers is illustrated in Figure 4.4. As the dose of a chemical increases, the organism moves from a state of homeostasis to a state of stress. With further increases in dose, the organism enters first the state of reversible disease, and eventually the state of irreversible disease, which will lead to death. In concept, all of these stages can be monitored by biomarker assays (lower part of conceptual diagram). 

The design of such cytotoxic antibodies is conceptually simple attach a toxic substance or a mediator of toxicity to the appropriate monoclonal and you have a magic bullet that can find and eliminate the one-in-a-billion cells that have the requisite marker (Figure 21.1). The antibody provides the recognition and binding capacity, while the associated toxic component effects cellular alterations leading to cell death (Pastan et al., 2006). 

Figure 21.2 Conceptualized construction of an A-B subunit protein toxin (left). The B chain contains a binding region for docking onto cell surfaces, while the A chain contains a catalytic site that produces cytotoxic affects intracellularly. The two subunits are joined by a disulfide bond that is reductively cleaved at the cellular level to allow the A subunit to affect cell death. A molecular model of ricin is on the right.

The DSM is careful to recognize that culture also determines definitions of mental illness. In the DSM, unusual and distressing behaviors such as culturally sanctioned responses to the death of a loved one are excluded from diagnosis. Most current conceptualizations of mental illness recognize that societal values play an important role in establishing whether something is a mental disorder (Lilienfeld Marino, 1995 Wakefield, 1992). The result is that the boundaries of mental illness are believed to shift as a function of culture, both across cultures and within cultures, over time. One important implication of cultural relativism is that definitions of mental illness will necessarily vary. 

The latter statement evokes the image of inexorable entropy increase as the ultimate progress variable of the universe. Entropy presumably evolves toward an eventual equilibrium limit that marks the end of spontaneous change in our universe heat death (Warmetod). Sidebar 4.9 warns against common conceptual errors that result from superficial application of the entropy-increase principle (4.48). 

As far as we know and as far as we can extrapolate, animals do not have any concepts of death. They exhibit behavior of fear, and when in pain suffer for the moment, but there is no evidence that they experience the disease of conceptualizing death. 

Figure 2.12 A conceptual physiologically based pharmacodynamic (PBTD) model for CC14 and kepone interaction. KMIT = rate constant for mitosis KREP Rate constant of inj. cells repair KBIR = rate constant for cell birth KINJ = rate constant for cell injury by toxicants KDIEI = rate constant for general cell death KDIE-1 = rate constant for cell death due to injury KPH = rate constant for phagocytosis. (Redrawn from El-Masri et al. [1996a], with permission.)...

Figure 3.6 Conceptual two-stage carcinogenesis model. A normal or initiated cell is subjected to division into two susceptible cells without mutation (event 1), death/ differentiation (event 2), division into two susceptible cells with one mutated (event 3), or no change.

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