Guests have included San Francisco Homicide Detective Vince Ripetto, on the topic of serial killers of prostitutes, domestic violence and San Francisco's controversial 'School for Johns'. Supervisor Tom Ammiano, another recent guest on Street Wise, said that the show is a vital part of San Francisco's alternative media, providing a broad range of viewpoints on important issues about the 'streets' of San Francisco. At the show's inception, Street Wise filled a media void providing a medium for San Francisco Supervisor candidates to vocalize their opinions on issues of concern to the City. Supervisors Micheal Yaki and Leland Yee appeared with fellow Supervisorial candidates to discuss such issues as Access to Health Care, and local effects of Federal Immigration Policy reforms. In addition, Street Wise has featured such guests as founder of the Cannabis Buyers Club, Dennis Peron, publisher of The Spectator, Kat Sunlove, and the principal organizers of the Exotic Dancers Alliance, whose work resulted in the unionization of dancers at local strip club, the Lusty Lady.
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