Methods and achievements in experimental pathology最新文献

The so called 'normal', 'physiological' or 'programmed' cell death constitutes now a major field of developmental and cell biology. In the present article we review recent information on the biological significance of cell death in development. Special attention is paid to the range of techniques available for studies on cell death, the role of cell death during normal and abnormal development and to the mechanisms controlling cell death, including epigenetic and genetic factors.

Tumor necrosis factor alpha is increasingly being recognized as an important macrophage-derived cytokine that possesses pleomorphic effects in both physiologic and immunologic systems. Current evidence has demonstrated that tumor necrosis factor may stimulate a plethora of cellular responses in vitro and induce multiple physiologic derangements when given in vivo. While the biologic activity of tumor necrosis factor elaborated by macrophages and macrophage cell lines in response to bacterial and protozoal cell products have been well documented, the endogenous factors that regulate the production of this monokine are not as clearly delineated. This chapter focuses on the cellular and molecular mechanisms that endogenously regulate the production of tumor necrosis factor.

This chapter presents the methodology as well as various applications of a silicone rubber (Microfil) prefusion technique for evaluation of the microcirculation. In the heart, Microfil perfusion has been used in conjunction with clearing techniques to elucidate normal anatomic relationships, to identify areas of myocardium at risk following vascular occlusion, and to observe dynamic events in the development of various cardiomyopathies. Advantages of the technique include in vivo applicability, ease of vascular filling, and ability to discriminate between adjacent vascular fields. Preliminary data from work in other organ systems including skeletal muscle, brain, liver, and lung are also presented.

Cell death plays a variety of important roles in biology, both physiological and pathological. Physiological cell death is an important part of development, cell turnover and various aspects of immunological defenses. Pathological cell death is an element of some of the most important diseases plaguing modern society. Recent studies on the mechanisms of calcium-mediated cell death, thought to be important for both physiological and pathological cell death, have indicated that it is a multi-step process in which the cells are active participants, triggering their own self-destruction. Such mechanisms suggest the potential for pharmacological intervention, either to prevent disease-induced tissue death or to remove unwanted tissues.

Irreversible damage of the myocardial cells may show different morphologic aspects in relation to the type of dysfunction of their contraction-relaxation cycle. Attenuation of the muscle fibers with elongation of the sarcomeres and nuclei are the earliest modifications (systolic paradoxical bulging and stretching by the intraventricular pressure) when the myocells stop their function in irreversible relaxation. This 'atonic' death is pathognomonic of myocardial infarction (infarct or coagulation necrosis) and the lesion evolves with typical structural changes. An opposite and entirely different morphologic pattern is seen in the 'tetanic' death in which the myocardial cells arrest in irreversible contraction (coagulative myocytolysis or contraction band necrosis). Segmental (paradiscal bands) or pancellular hypercontraction with extreme shortening of the sarcomeres and subsequent myofibrillar rhexis alternated with irregular cross band formations (holocytic bands) are characteristic of this necrosis seen in numerous human and experimental conditions and specific of catecholamine toxicity. The third type of damage is observed in low output syndromes in which increasing edematous vacuolization and disappearance of the myofibrils (colliquative myocytolysis) are the main structural alterations. They are suggestive of progressive functional reduction leading to dilatative insufficiency ('failing' death). These clear-cut morphofunctional patterns indicate distinctive biochemical impairments and pathogenesis. In particular their frequent presence in and possible association with the different aspects of the ischemic heart disease presuppose other non-ischemic mechanisms responsible for complications and death in this modern epidemic.