Abstract

Received for publication June 28, 1962. I wish to thank Professor C. Mignone, Director of the Department of Pathological Anatomy, for the working facilities he has granted me at his Institute and for the interest he has taken in my studies. I am indebted to the Institute Pinheiros, Productos Terapeuticos S. A., Sao Paulo, for the generous supply of animals and for furnishing toxin samples and bacterial cultures. I wish to express my gratitude to Dr. Rosalvo Guidolin and Mr. Jose Tavares from the Institute Pinheiros for their efficient help throughout these experiments. * This study was supported by research grant H5-5477 from the National Institutes of Health, U. S. Public Health Service. ously with 8 MLD of toxin. Control animals included (1) 20 normal guinea pigs; (2) 60 guinea pigs that had received sublethal doses (0.008 to 0.2 MLD) of diphtheria toxin either subcutaneously or intracerebrally, or else the same volume of physiological saline (0.1 ml) intracerebrally; (3) 15 guinea pigs with various lung diseases enumerated below; and (4) 6 rabbits intravenously injected with Serratia marcescens endotoxin. Most of the animals injected with 1 MLD or higher doses of diphtheria toxin, as well as the animals injected with living cultures of diphtheria bacilli, died within the first 4 days after inoculation. Guinea pigs injected with one-third to one-half MLD of diphtheria toxin usually survived for more than 2 months. Only a few of them (about 2 in 10) died 8 to 14 days after inoculation. Two months after the toxin injection all surviving animals were killed with ether. Two samples of commercial diphtheria toxin, containing 350 MLD per ml and 250 MLD per ml, respectively, were used for these experiments. The strain of Corynebacterium diphtheriae used for inoculations was the Park 8 strain which had been grown for 24 hours on Martin' s broth. The dead animals were autopsied within 1 to 12 hours after death, and their organs were fixed in lO0/^ formol or Bouin' s formol-picric acid solution for 24 to 48 hours.

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