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At least 1,423 records · Page 79Linked to original sources
PubMed1981

Active antitoxic immunization by a diphtheria toxin synthetic oligopeptide.

Diphtheria toxin (DT) is a single polypeptide chain of molecular weight 62,000 with two disulphide bridges. Immunization against diphtheria rests on the stimulation of antibodies against detoxified toxin which also combine with the native toxin. Because the antibodies differ functionally from each other, however, only some of them are able to neutralize toxicity. We have therefore set out to synthesize part of the amino acid sequence of the toxin whose function as a stimulator of antibodies might be less ambiguous, and have chosen the loop of 14 amino acids subtended by the disulphide bridge nearer the NH2 terminus of the molecule (Fig. 1). There is reason to think that this loop may be involved in the toxicity and immunological specificity of the molecule. We report here our finding that the tetradecapeptide (residues 188-201), when linked covalently with two different carriers, will elicit in guinea pigs antibodies which not only bind specifically with the toxin but neutralize its dermonecrotic and lethal effects. To our knowledge these results constitute the first example of successful active immunization against a lethal bacterial toxin using a synthetic antigen.

Amino Acid Sequence↗
PubMed1996

The potential role of Clostridium perfringens alpha toxin in the pathogenesis of acute pancreatitis.

BACKGROUND: Clostridium perfringens is a bowel commensal that can colonise the biliary tract. It produces the alpha toxin (phospholipase C), which can induce spontaneous tissue necrosis. AIMS: To investigate whether there is any evidence that Clostridium perfringens alpha toxin can be detected in acute pancreatitis. METHODS: Serum samples from 21 patients with acute pancreatitis and 22 controls were assayed for C perfringens phospholipase C as well as anti-phospholipase C IgG and IgM; IgG and IgM anti-toxins were measured by enzyme linked immunosorbent assay. RESULTS: In normal healthy controls there is a very high level of natural anti-toxin of both the IgG and IgM class. Of the 21 patients with acute pancreatitis alpha toxin was detected in five (23.8%). Levels of both IgG and IgM anti-toxin were significantly reduced in acute pancreatitis. CONCLUSIONS: The results suggest that there is an abnormality of the immune status to C perfringens alpha toxin in patients with acute pancreatitis. This may be the result of a release of alpha toxin, although it is difficult to state whether this is a primary or secondary phenomenon in these patients. These preliminary results merit further investigation.

Acute Disease↗
PubMed1977

Structure of tetanus toxin. II. Toxin binding to ganglioside.

The interaction between tetanus toxin and ganglioside containing 2 N-acetylneuraminic acid residues linked in sequence to one another has been investigated using a new method involving radioactively labeled ganglioside and tetanus toxin adsorbed to Sephadex matrix. Binding between the two components was demonstrated, and it was calculated that in the nanomolar concentration range, tetanus toxin becomes half-saturated at about 5 X 10(-8) M concentration of ganglioside. Removal of the ceramide portion from the ganglioside resulted in the complete loss of binding activity, whereas removal of the terminal N-acetylneuraminic acid residue from the intact ganglioside had no effect. Among the fragments derived from tetanus toxin (Helting, T. B., and Zwisler, O. (1977) J. Biol. Chem. 252, 187-193), only the heavy chain polypeptide exhibited a binding activity of the same order of magnitude as that observed for the native toxin. The light chain polypeptide showed no interaction with ganglioside and among the fragments derived from the toxin by digestion with papain, only Fragment C, at a high protein concentration, displayed marginal binding activity. Using monovalent antibodies directed against specific regions of the tetanus toxin molecule, it was demonstrated that antibodies directed against Fragment C uniquely interfere with the binding process. Anti-light chain serum was ineffective, as well as antitetanus toxoid serum previously absorbed with Fragment C. It is concluded that the binding site for ganglioside is located on the heavy chain portion of tetanus toxin, possibly in or near the region comprised by Fragment C.

Binding Sites↗
PubMed1964

EXPERIMENTAL GLOMERULONEPHRITIS. IV. PARTICIPATION OF COMPLEMENT IN NEPHROTOXIC NEPHRITIS.

Rats with nephrotoxic serum nephritis may show fixation of complement (C') in the glomeruli during two periods. The first period occurs immediately after the injection of the antisera and extends until the host response occurs. The second period is related to the deposit of rat gamma globulin in the glomeruli presumably occurring at the time of the immune response to the heterologous nephrotoxic serum (NTS). This second period terminates about 2 to 3 weeks after injection of NTS, presumably at the time the rat stops making antibodies to the nephrotoxic gamma globulin fixed in the glomeruli. After this period, the glomerular lesion is incapable of fixing detectable amounts of circulating C' unless the antibody response to the heterologous globulin is reactivated. The immunological events which take place in the initial 2 to 3 week period appear to produce a permanent and irreparable lesion in the glomeruli leading to chronic nephritis. Rabbit NTS produces fixation of rat C' during both periods. Duck NTS shows no detectable fixation of rat C' until rat gamma globulin fixes in the glomeruli at the time of the host immune response to the heterologous nephrotoxic gamma globulin. Decomplementation of rats injected with rabbit NTS produces an amelioration of the initial period of nephrotoxic serum nephritis. The fixation of C' in the glomerular lesions was studied with the use of fluorescent antibody methods. The detection of host beta-1C globulin and gamma globulin in the glomerulus pointed to an immune reaction but not necessarily an active one. The tissue C' fixation test using kidney slices and guinea pig C' proved to be a more sensitive method of detecting tissue reactants capable of fixing C', but its relationship to in vivo events is not certain.

Animals↗
PubMed1965

DETECTION OF STAPHYLOCOCCAL ENTEROTOXIN IN FOOD.

Methods are described for the extraction and serological detection of trace amounts of enterotoxins A and B in foods incriminated in outbreaks of staphylococcal food poisoning. Evidence is presented for the probable applicability of the methods for the detection of unidentified enterotoxins.

Adsorption↗
PubMed1964

TAXONOMY OF CLOSTRIDIUM BIFERMENTANS AND CLOSTRIDIUM SORDELLII. II. TOXIGENIC AND SPORULATING POTENCIES IN SUBSTRAINS OF A CLOSTRIDIUM SORDELLII STRAIN.

Tamai, Kenzo (Kanazawa University, Kanazawa, Japan), and Shoki Nishida. Taxonomy of Clostridium bifermentans and Clostridium sordellii. II. Toxigenic and sporulating potencies in substrains of a Clostridium sordellii strain. J. Bacteriol. 88:1647-1651. 1964.-The existence of six biological criteria for distinction of Clostridium bifermentans and C. sordellii was confirmed. The difference in the six criteria gradually disappeared as the sporulating potency of the substrains of C. sordellii 4708 was strengthened. The substrains which could resist heating at 90 C for 10, 20, or 30 min were found to have lost all six criteria for distinction and were biologically in agreement with C. bifermentans. We further demonstrated that all newly isolated strains of C. bifermentans examined possessed extremely strong sporulating potency.

Antitoxins↗