An experimental model of "chronic" diphtheria intoxication in the guinea pig was developed. Adult guinea pigs, subjected to a regimen of multiple sublethal doses of purified diphtheria toxin (total of 1.4 minimum lethal doses divided equally in four daily doses), developed a toxemia which terminated in death between 6 and 8 days. During an advanced stage of illness, de novo protein synthesis wa...

Natural diphtheria toxin is synthesized as a single polypeptide chain that is activated by cleavage into an A- and a B-fragment, which are linked by a disulphide bond. In the present work the ability of independently translated A- and B-fragments to associate was investigated. Low amounts of A- and B-fragments synthesized in vitro were mixed under conditions that allowed formation of a disulphi...

Lysosomotropic amines, such as ammonium chloride, are known to protect cells from the cytotoxic effects of diphtheria toxin. These drugs are believed to inhibit the transport of the toxin from a receptor at the cell exterior into the cytoplasm where a fragment of the toxin arrests protein synthesis. We studied the effects of lysosomotropic agents on the cytotoxic process to better understand ho...

As determined by the intracutaneous test in guinea pigs, diphtheria toxin is not altered in the presence of cardiac tissue obtained from the fetal or from the adult heart of the guinea pig. Tissue cultures were apparently uninjured by the presence of the toxin in the dilutions used in these experiments, and, when washed with embryo extract after removal of the diluted toxin, continued to grow. ...

The effect of diphtheria toxin on certain metabolic processes in growing HeLa cells has been described. It was found that both aerobic respiration and glycolysis are insensitive to toxin action. The incorporation of S(35)-methionine was found to be completely inhibited by toxin prior to the appearance of any visible cell damage. It was also observed that toxin levels above 0.3 Lf per ml. had no...

Recent studies have demonstrated that diphtheria toxin is an enzyme of unusual type. Small amounts of the toxin, added to nicotinamide adenine dinucleotide (NAD)-containing mammalian cell extracts, block peptide-bond formation by catalyzing inactivation of the translocating enzyme, aminoacyltransferase 2 (T2) (1-3). This highly specific reaction involves the splitting of NAD with liberation of ...

De novo expression of the interleukin 2 receptor (IL-2R) is a critical and pivotal event in initiation of an immune response. Targeting the low-affinity IL-2-binding p55 subunit of the high-affinity IL-2R with the rat anti-mouse IgM monoclonal antibody M7/20 suppresses a variety of T-cell-mediated reactions, including transplant rejection, autoimmunity, and delayed-type hypersensitivity (DTH). ...

Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxi...

Crude messenger ribonucleic acid fractions isolated from Corynebacterium diphtheriae and Escherichia coli were translated in an E. coli in vitro protein-synthesizing system and yielded precursors of the secreted proteins diphtheria toxin and alkaline phosphatase, respectively. Addition of inverted E. coli inner membrane vesicles to the system during the initial stages of translation resulted in...

Guinea pigs infected by intradermal injection of living toxigenic diphtheria bacilli and protected by horse antitoxic globulin, given either before or after infection, develop delayed hypersensitivity of the tuberculin type to diphtherial proteins. The highest degree of hypersensitivity is specifically directed against diphtheria toxin (or toxoid) itself, although smaller delayed skin reactions...