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(1950, 1954), who developed a detailed theoretical framework linking speci c psychodynamic processes with predictable physiological sequelae and illness states When Sifneos (1972) articulated his empirically grounded, psychoanalytically informed model of alexithymia (ie, an inability to verbalize emotions), the stage was set for the development of a truly psychoanalytic health psychology The key hypotheses of Sifneos s approach that unverbalized emotions can have myriad destructive effects on the body s organ systems helped lay the groundwork for several ongoing health psychology research programs that are to varying degrees rooted in psychodynamic concepts Research on health and hardiness (Kobasa, 1979), stress and coping (Pennebaker & O Heeron, 1984), emotional disclosure and recovery from illness (Spiegel, Bloom, Kraemer, & Gottheil, 1989), and the Type C (cancer-prone) personality (Temoshok, 1987) are all based in part in psychodynamic models of health and illness.

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also represent ideal platforms for ADMET (adsorption, distribution, metabolism, excretion, and toxicity) testing of novel drug candidates Consequently, our laboratory s strategy toward the fabrication of engineered liver tissue is to develop (1) enabling platforms for the controlled recapitulation of these critical extracellular cues and (2) in vitro models to study the complexities of environmental interactions Furthermore, current studies in our laboratory are addressing the potential utility of alternative cell sources, such as embryonic stem cells and various adult stem cell populations, for liver tissue engineering Overall, important criteria for the development of a particular system include (1) the desired application (in vitro model, basic science, or therapeutic) and (2) the important liver properties that must be established for that certain application, such as stabilized phenotype, structural complexity (zonation), directional uid ow, and in some cases 3-D organization.

The Opportunities and Challenges of Neuroscience Some of the rst contemporary efforts to integrate psychoanalytic principles with ndings from neuroscience involved sleep and dreams (Hobson, 1988; Winson, 1985) Although the language of Freudian dream theory is far removed from that of most neuropsychological models, work in this area has revealed a number of heretofore unrecognized convergences between the psychodynamics and neurology of dreaming In fact, contemporary integrative models of dream formation now incorporate principles from both domains, setting the stage for extension of this integrative effort to other aspects of mental life Neuroimaging techniques such as the computerized axial tomography (CAT) scan, the positron-emission tomography (PET) scan, and magnetic resonance imaging (MRI) have begun to play a leading role in this ongoing psychoanalysisneuroscience integration.

Our laboratory has developed several distinct model systems that recapitulate critical structural and/or functional aspects of the liver Speci cally, as a means to investigate systematically the role of heterotypic contact in hepatocyte cocultures, our laboratory has developed and characterized a versatile micropatterning method, which has enabled the quantitative control of the spatial relationship of hepatocytes and broblasts [Bhatia, 1997] This method is one in a repertoire of techniques that we have developed to control cell-cell interactions These processes enable an examination of the mechanisms of interaction, including the potential importance of numerous aspects such as continuous signaling, gap junctions, and soluble factors Furthermore, the micropatterning method described in this chapter also represents a robust platform for the in vitro functional stabilization of hepatocytes.

3.5.2. Proteoglycan Dilution Buffer NaAc, 0.05 M, with 0.05% Tween 20, at pH 6.8 3.5.3. Dimethylmethylene Blue (DMMB) Dye Reagent DMMB, 16 g/ml, in 0.03 M sodium formate, 0.2% V/V formic acid, pH 6.8. To prolong the activity of the DMMB dye, it is desirable to rst solubilize the reagent in organic solvents before diluting it into a mostly aqueous environment.

Moreover, to gain another level of control of environmental in uences and further enhance the physiologically relevant function of hepatocytes in vitro, we have also developed additional approaches First, we have recently described the construction of a perfusion bioreactor system that has enabled the formation of steady-state oxygen gradients, resulting in the presence of zonated hepatocyte characteristics [Allen and Bhatia, 2003), which is an important feature of the liver in vivo For example, numerous drugs exhibit zonal toxicity due to compartmentalization of drug-metabolizing enzymes [Lindros, 1997] As a result, the in vitro model of zonation described here represents a unique system to investigate, among many aspects, the mechanisms of zonal hepatotoxicity Each of these approaches (micropatterning and bioreactor systems) recapitulates two-dimensionally certain aspects of hepatocyte function.

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