with the physeal abnormalities, they were used to examine a mechanism that would put a particular finding into proper clinical perspective. And third, with both the physeal abnormalities and the heart valve lesions, they were used to determine whether a particular finding was structurally based or a class-wide pharmacological effect. Such a determination is not always straightforward, since finding that multiple compounds in a class cause the same problem is not the same as showing that the problem is class-wide. To elaborate, a number of compounds caused pulmonary hemorrhage, and it would have been easy to conclude that the effect must be class-wide. Yet it turned out that this was probably not a pharmacological effect, but was associated with a structure–activity relationship. Thus it is important to explore the mechanism behind an effect, particularly if one is trying to answer a class-wide pharmacological question. Furthermore, it is important to sample the target populations cleanly, as there are multiple cell populations within every organ, and confocal imagery or laser capture microdissection (LCM) can be used to identify and isolate the individual cell populations of interest.



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