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Even when she was only in her early forties, Isabel Randolph specialized in middle-aged "grand dame" roles on stage and radio, continuing in this vein when she entered films in 1940. Randolph gained nationwide popularity as the pompous Mrs. Uppington (aka "Uppy") on radio's Fibber McGee and Molly. She re-created this character onscreen in RKO's Look Who's Laughing (1941) and Here We Go Again! (1942), and in the Republic cornpone musical O, My Darling Clementine (1943). She went on to play scores of small roles in A-pictures and major assignments in B's; in at least one Republic Western of the early '50s, she was cast radically against type as a criminal mastermind. On TV, Isabel Randolph was seen as private-school proprietress Mrs. Nestor during the final (1955-1956) season of Our Miss Brooks.