Diphtheria

Page 1170 (Figure 28 5) is adapted from crystallographic coordinates deposited with the Protein Data Bank PDB ID IDDN White A Ding X Vanderspek J C Murphy J R Ringe D Structure of the Metal Ion Activated Diphtheria Toxin Re pressor/Tox Operator Complex Nature 394 p 502 (1998)... 

During the early 1900s, vaccines against major human epidemic diseases such as pertussis, diphtheria, tetanus, and tuberculosis were developed. Vaccines for many animal diseases were also available. In the early 1950s, the development of cell culture techniques byj. E. Enders at Harvard was followed by another series of major advances in vaccine development. Vaccines against poHo, mumps, measles, and mbeUa were Hcensed during the 1960s. 

Vaccines can be roughly categorized into killed vaccines and Hve vaccines. A killed vaccine can be (/) an inactivated, whole microorganism such as pertussis, (2) an inactivated toxin, called toxoid, such as diphtheria toxoid, or (J) one or more components of the microorganism commonly referred to as subunit vaccines. The examples are capsular polysaccharide of Streptococcus pneumoniae and the surface antigen protein for Hepatitis B vims vaccine. 

Diphtheria, Tetanus, and Pertussis. These vacciaes Hi combiaatioa (DTP) have beea routiaely used for active immunization of Hifants and young children sHice the 1940s. The recommended schedule calls for immunizations at 2, 4, and 6 months of age with boosters at 18 months and 4—5 years of age. SHice 1993 these vacciaes have beea available Hi combination with a vacciae that protects agaiast Haemophilus disease, thus providing protectioa agaiast four bacterial diseases Hi oae preparatioa. A booster immunization with diphtheria and tetanus only is recommended once every 10 years after the fifth dose. 

Composition and Methods of Manufacture. The diseases of diphtheria and tetanus are caused by toxHis synthesized by the organisms CoTynebacterium diphtheriae and Clostridium tetanic respectively. Diphtheria and tetanus vacciaes coataHi purified toxHis that have beea iaactivated by formaldehyde to form toxoids. 

Diphtheria and Tetanus Toxoids and Pertussis Waccine Mdsorbed, USP Package Insert, Coimaught Laboratodes, Surftuster, Pa., revised 1994. 

A different kind of enzyme, translocase [80700-39-6], which transfers a fragment of NAD to the protein—synthesis factor (elongation factor 2), is catalyzed by diphtheria toxin, thereby inhibiting protein synthesis (43). In tumor cells, the rate of protein synthesis is 100 to 1000 times more sensitive to diphtheria toxin than the analogous process in normal cells (41) therefore, diphtheria toxin is selectively toxic to tumor cells. 

Protective and exploitive proteins Immunoglobulins Thrombin Eibrinogen Antifreeze proteins Snake and bee venom proteins Diphtheria toxin Rtcin... 

FIGURE 10.32 The structures of (a) S-eudotoxiu (two views) from Bacillus thuringiensis and (b) diphtheria toxin from Cmynehacterium diphtheriae. Each of these toxins possesses a bundle of a-hehces which is presumed to form the trausmembraue channel when the toxin Is Inserted across the host membrane. In S-endotoxln, helix 5 (white) Is surrounded by 6 helices (red) In a 7-hellx bundle. In diphtheria toxin, three hydrophobic helices (white) lie at the center of the transmembrane domain (red). 

Protein toxins acting intracellularly are often composed of two subunits (A/B model). One subunit is catalytic (A-subunit) and the other is responsible for binding and cell entry (B-subunit). Following binding to an extracellular membrane receptor, the toxins are endocytosed. From the endosomes, the A-subunit is directly (pH dqDendent) transferred into the cytosol (e.g., diphtheria toxin and anthrax toxin) or the toxin is transported in a retrograde manner via the golgi to the ER (e.g., cholera toxin), where translocation into the cytosol occurs [1]. 

Diphtheria toxin, Pseudomonas exotoxin A Elongation factor 2 ADP-ribosylation Inhibition of protein synthesis (diphtheria, Pseudomonas infection)... 

Diphtheria and tetanus Diphtheria and Immunization against Sfee adverse reactions for See package inserts... 

Diphtheria and Certiva, Active immunization against Sse adverse reactions for Follow package... 

Vaccine diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus combined Pediarix Active immunization against diphtheria, tetanus, pertussis and all known subtypes of hepatitis B virus, and poliomyelitis immunization Sfee adverse reactions against individual vaccines. Primary immunization series 3 doses of 0.5 mLat 6-to 8-week intervals IM (first dose is 2 months of age, but may be given as early as 6 weeks of age)... 

Diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP). The... 

General interventions, such as increasing the fluids in the diet, allowing for adequate rest, and keeping the atmosphere quiet and nonstimulating, may be beneficial. The primary health care provider may prescribe acetaminophen, every 4 hours, to control these reactions. Local irritation at the injection site may be treated with warm or cool compresses, depending on the patient s preference. A lump may be palpated at the injection site after a diphtheria, pertussis, tetanus (DPT) injection or other immunization. This is not abnormal and will resolve itself within several days to several months. 

Tributyltin(IV) derivatives of six different pharmaceutically active carboxylates were synthesized and their antibacterial activities were tested using 10 different bacteria (B. cereus, C. diphtheria, E. C. ETEC, K. pneumonia, P. mirabilis, P. aeroginosa,... 

A human contraceptive vaccine based on lactide polymers is currently being developed. The antigen is a 37-amino-acid peptide of B-HCG conjugated to diphtheria toxoid. The antigen is administered wtih microencapsulated muramyl dipeptide as an adjuvant. Studies in rabbits have shown 9-12 months of elevated antibody liter following... 

Wahn U, Aalberse RC Down-regulation of IgE and IgG4 antibodies to tetanus toxoid and diphtheria toxoid by co-vaccination with cellular Bordetellapertussis vaccine. J Immunol 2001 15 167 2411-2417. dS... 

Diphtheria toxin, an exotoxin of Corynebacterium diphtheriae infected with a specific lysogenic phage, catalyzes the ADP-ribosylation of EF-2 on the unique amino acid diphthamide in mammalian cells. This modification inactivates EF-2 and thereby specifically inhibits mammalian protein synthesis. Many animals (eg, mice) are resistant to diphtheria toxin. This resistance is due to inability of diphtheria toxin to cross the cell membrane rather than to insensitivity of mouse EF-2 to diphtheria toxin-catalyzed ADP-ribosylation by NAD. 

Microbial toxins such as diphtheria toxin and activated serum complement components can produce large pores in cellular membranes and thereby provide macromolecules with direct access to the internal miheu. 

Corynebacterium diphtheriae, which is non-sporing, is the causal organism of diphtheria, a disease which has largely been eradicated by immunization (Chapter 16). 

Bordetellapertussis, Corynehacterium diphtheriae, Vibrio cholerae). This is, to a large extent, a reflection of their inability to combat that host s deeper defences. Survival at these sites is largely due to firm attachment to the epithelial cells. Such organisms manifest disease through the production and release of toxins (see below). 

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