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PubMed1983

Tetanus toxin-[2,3-3H]propionamid. Synthesis, specific activity, immunoreactivity, toxicity and ascent into the spinal cord.

Tetanus toxin was tritiated with various amounts of N-succinimidyl-[2,3-3H]propionate. A tenfold molar excess of reagent over toxin was used for the introduction of about 5 nmol of [2,3-3H]propionate into 1 nmol of toxin, corresponding to a specific activity of about 48 MBq/mg protein. The labelling procedure did not change significantly the immunoreactivity of tetanus toxin, but reduced the toxicity in mice from 12 ng/kg to 16 ng/kg. Tetanus toxin-[2,3-3H]propionamid was carried through the peripheral nerves into the spinal cord. It could be used instead of 125I-labelled toxin for the detection of anti-tetanus toxin antibodies with a detection limit of 0.25 mU/ml of serum.

Animals↗
PubMed1982

The effects of induced hypoxia on the cardiovascular system in dogs poisoned with tetanus toxin.

Tetanus toxicity was induced in dogs by injecting the toxin subcutaneously in the groin. On developing generalised toxic symptoms, these dogs were characterised by signs of increased sympathetic discharge to the cardiovascular system as evidenced by high basal values of blood pressure, heart rate and LV dP/dt max. Mild to moderate hypoxia induced by ventilation with 10% O2 in N2 had no appreciable effect on the cardiovascular variables. However, moderate to severe hypoxia induced by ventilation with 7% O2 in N2 further increased the sympathetic discharge to the heart and blood vessels resulting in increases in heart rate, LV dP/dt max and blood pressure. These responses were abolished by adrenergic blockers. The responses in the tetanus dogs were identical to those seen in dogs without tetanus toxicity. Atropine or moderate lactic acidaemia did not alter the responses to hypoxia. Beta-adrenergic blockers appear to be useful drugs in the control of tetanus patients who show evidence of increased sympathetic activity or who develop hypoxaemia.

Animals↗
PubMed1977

The labelling of motor end-plates in skeletal muscle of mice with 125I tetanus toxin.

Twelve hours after injection of 125I labelled tetanus toxin into the shank of one hindlimb of mice radioactivity was found in the end-plate region of soleus muscles. The ratio between the radioactivity of the end-plate and the end-plate-free region was 2.5 +/- 0.4 S.D. Autoradiographs showed intense labelling of end-plates and a slight but clear labelling of axons. When 125I tetanus toxin was injected 3 days after denervation of the soleus muscle the former end-plate region still accumulated a higher radioactivity (ratio 2.0 +/- 0.5 S.D.), however, autoradiographs showed a diffuse distribution of labelled tetanus toxin. It can be concluded that tetanus toxin binds to the presynaptic nerve terminal. This binding is not dependent on activity of the nerve terminal or transmitter release.

Animals↗
PubMed1985

Enzymatic hydrolysis of tetanus toxin by intrinsic and extrinsic proteases. Characterization of the fragments by monoclonal antibodies.

Enzymatic fragments of tetanus toxin were characterized by immunoblotting using a set of previously characterized antibodies (Ahnert-Hilger et al. (1983) and a set of novel antibodies. The selected antibodies recognized the light chain, fragment C (beta 1), and the complementary piece (beta 2) of the heavy chain when blotted on nitrocellulose. All toxin preparations contained intrinsic esteroprotease activity which became manifest in the presence of urea. The main split product was a fragment (MW 100 000) reacting with anti-fragment C and anti-beta 2 antibodies. Toxicity does not depend on this protease activity. Some crude preparations of tetanus toxin contain another split product (MW 47 000) which resembles fragment C. The main product of papain hydrolysis is fragment C, which appears as a double band under nonreducing conditions but is homogeneous when reduced. Chymotryptic digestion hydrolyses the heavy chain well but leaves the light chain largely intact. Tetanus toxin is very resistant against trypsin as compared with other proteases, although this enzyme splits numerous different links. Our data show the usefulness of immunoblotting with monoclonal antibodies in analytical work with tetanus toxin, and the relevance of intrinsic proteases.

Antibodies, Monoclonal↗
PubMed1999

Tetanus after a resection for a gangrenous perforated small intestine: report of a case.

We report herein the case of a 75-year-old man who developed severe tetanus 24 h after the resection of a gangrenous perforated small intestine. It seemed that the tetanus was caused by a spillage of the intestinal contents harboring Clostridium tetani; however, this was not identified by a culture. The diagnosis of tetanus was made only when opisthotonus in this patient became evident and normal tetanus treatment proved to be successful.

Aged↗
PubMedDate not supplied

The immunogenicity and safety of a new combined diphtheria, tetanus and poliomyelitis booster vaccine (Td-eIPV).

In view of the continuing risk of contracting tetanus, diphtheria and poliomyelitis, and the well-documented decline in immunity with time, the need for booster vaccinations is substantial. The immunogenicity and safety of a new combined booster vaccine against tetanus, diphtheria and poliomyelitis (REVAXIS) developed by Pasteur Mérieux Connaught (Lyon, France) were evaluated in four clinical studies. This vaccine (Td-eIPV) combines an adsorbed tetanus toxoid and low-dose diphtheria toxoid vaccine (Td) with an enhanced, inactivated polio vaccine against poliovirus types 1, 2 and 3 (eIPV). In 256 healthy young adults, a single dose of Td-eIPV was shown to be immunogenic, eliciting antibody levels considered protective against disease for each vaccine component in > or = 99.6% of the subjects. In 112 healthy older subjects (> 40 years of age), two doses of Td-eIPV elicited seroprotective levels of antibodies in 94% of the subjects for diphtheria, and in all subjects for tetanus and poliovirus types 1, 2 and 3. Safety data from all 368 subjects, as well as 31 phase I volunteers and 1,742 subjects included in a safety study, reveal that the vaccine is safe. Most reactions were predictable, temporary and mild. There was no evidence that the vaccine was associated with any clinically serious event or modification of clinical laboratory parameters. The data reviewed here show that Td-eIPV is immunogenic and safe when administered as a booster vaccination in healthy adults of all ages.

Adult↗
PubMedDate not supplied

Functional characterization of specific IgE antibodies for tetanus toxoid.

The specific IgE response that appears in subjects immunized with tetanus toxoid does not induce hypersensitivity reactions at subsequent immunizations. The type I immune response, therefore, was studied both in vivo and in vitro, in 11 subjects who had specific IgE antibodies for tetanus toxoid. The results showed that: 1. the specific IgE antibodies are heterogeneous regarding their affinity for the mast cell and basophil receptors; 2. the specific IgG antibodies for tetanus toxoid, at serum concentrations, are not able to interfere with the in vitro specific basophil degranulation; 3. in the PEG precipitate there are aggregates of specific IgE antibodies for tetanus toxoid. In vitro, these molecular aggregates are not able to sensitize the basophil cells.

Adolescent↗
PubMed2002

Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil.

INTRODUCTION: Tetanus is still a significant health hazard in developing countries, with high associated mortality. OBJECTIVE: Describe the management of patients with severe tetanus in intensive care units (ICUs), in two different periods. SETTING: ICUs of two general hospitals. DESIGN: Concurrent cohort study. METHODS: Follow-up of all patients hospitalized with the diagnosis of severe tetanus in the ICUs from October 1981 to March 2001. We collected data prospectively, regarding the site of injury, clinical features, frequent clinical and infectious complications, concomitant illnesses, and mortality. The patients were divided into two groups according to the treatment protocol used; before 1993 and after 1993. RESULTS: There were 126 patients in group 1 (93 males) with a mean age of 39.0 +/- 18.8 years. There were 110 patients in group 2 (95 males) with a mean age of 48.4+/-17.8 years. Incubation period, onset period, and symptomatic period were higher in group 2 ( P < or = 0.02). The duration of neuromuscular junction blockade, benzodiazepine administration, mechanical ventilation, and ICU stay were longer in group 2, P < 0.001. Infectious complications were more frequent in group 2 ( P < 0.001). The mortality rate in group 1 was 36.5% and in group 2, 18.0% ( P = 0.002). Mortality was directly associated with symptomatic period, acute renal failure cardiac arrest and hypotension, and inversely associated with onset period in the multivariate analyses. CONCLUSIONS: The reduced mortality in severe accidental tetanus patients in group 2 is probably related to advances in ICU management, despite the higher incidence of infectious complications, which are probably related to the longer ICU stay.

Accidents↗
PubMed1998

Tetanus immunity in patients with hematological malignancies.

The aim of this study was to investigate long-term immunity to tetanus toxoid among patients with hematological disease who had been treated with conventional doses of chemotherapy. Altogether 206 patients with different hematological malignancies were included in the study. There were marked differences between the rates of seronegativity against tetanus, varying from 20% to 70% in different groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of 80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2 of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005) and advanced disease stage (P = 0.0001) were independent risk factors for loss of tetanus immunity in patients with hematological malignancies.

Adolescent↗
PubMed2005

Determination of tetanus antibodies by a double-antigen enzyme-linked immunosorbent assay in individuals of various age groups.

In this study, tetanus immunity was determined in 549 randomly chosen individuals of various age groups in Ankara, Turkey. Antibody levels in sera of the individuals were measured using a double-antigen enzyme-linked immunosorbent assay. Overall, 66.5% (95%CI, 62.4-70.4) of the population studied was found to have basic protection (>or=0.01 IU/ml) against tetanus. Protective levels of tetanus antibodies declined progressively with age. The rate of protection in children and adolescents (aged<20 years) exceeded 90%, while only 16.3% (95%CI, 8.9-26.2) of those over 60 years of age were protected. Females over 60 years of age were less immune than males of the same age group (p=0.034). Although the rates of protection in children and adolescents are regarded as satisfactory, the rates among adults are low. Preventive measures against tetanus should therefore focus on scheduled booster immunization for adults as well as children.

Adolescent↗
PubMed1985

Tetanus toxin affects the K+-stimulated release of catecholamines from nerve growth factor-treated PC12 cells.

Tetanus toxin specifically binds to neuronal surfaces and interferes with the release of transmitters. The effect of tetanus toxin pretreatment of PC12 cell line, taken as a model of neuronal cells in culture, was studied and found that it depresses depolarization-dependent catecholamines secretion. This effect is limited to PC12 cells fully differentiated by the action of Nerve Growth Factor (NGF) and is indicative of the expression of specific binding sites for tetanus toxin during transition from the undifferentiated state. Specific binding of [125I] tetanus toxin to NGF-treated PC12 was demonstrable. The toxin has no effect on the 45Ca accumulation coupled with the depolarization dependent release of catecholamines.

Adrenal Gland Neoplasms↗
PubMed1977

Selective trans-synaptic migration of tetanus toxin after retrograde axonal transport in peripheral sympathetic nerves: a comparison with nerve growth factor.

Adult rats were injected unilaterally into the anterior eye chamber and the submandibular gland with either [125I]tetanus toxin or [125I]nerve growth factor (NGF). Fourteen and 24 h later in electron microscopic autoradiographs of the superior cervical ganglia of the injected side the labeling was confined to a limited number (15-20%) of adrenergic ganglion cells and the silver grains were localized over axons, perikarya and dendrites providing evidence for a retrograde intraaxonal transport of the two macromolecules. Moreover, after injection of [125]tetanus toxin there was a very marked labeling of the presynaptic cholinergic nerve terminals. In contrast, after [125I]NGF these terminals were free of label. In both cases no specific labeling could be detected over glia and extracellular space. In the postganglionic axons the radioactivity seemed to be mainly associated with vesicles and smooth endoplasmic reticulum, in the perikarya and dendrites of the adrenergic neurons with secondary lysosomes, vesicles and smooth endoplasmic reticulum. The Golgi cisternae and the nuclei were free of radioactivity. The specific labeling of presynaptic terminals after injection of [125I]tetanus toxin together wirans-symaptic migration of [125I]tetanus toxin from the adrenergic ganglion cell to its innervating presynaptic terminals following retrograde intraaxonal transport.

Animals↗
PubMed1984

Botulinum toxin and tetanus toxin recognize similar membrane determinants.

The binding fragment of tetanus toxin (50,000 dalton carboxy-terminus of heavy chain) does not block neuromuscular transmission, but it does antagonize the ability of native tetanus toxin to block neuromuscular transmission. The binding fragment of tetanus toxin also antagonizes certain botulinum toxins, including types C and E. Antagonism is at the cell surface, suggesting that the various molecules compete for a similar membrane binding site. The data indicate that the binding site is specific for botulinum toxin rather than tetanus toxin.

Animals↗
PubMed1995

Effect of tetanus toxin on basal and evoked release of 5-hydroxytryptamine and dopamine in rat hippocampus in vivo.

Tetanus toxin is a potent neurotoxin which produces seizures and usually death in mammals. In the present study, we have investigated the effect of tetanus toxin on extracellular basal and evoked release of 5-hydroxytryptamine (5-HT), dopamine (DA) and their metabolites in vivo, 7 days after toxin injection into the hippocampus of rats. Tetanus toxin decreased both basal and evoked release of 5-HT and DA. The 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was not significantly decreased in the extracellular space. Of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) concentration was decreased while that of homovanillic acid (HVA) was unchanged. These findings are considered in light of the possible contributory role that a decrease in monoamine concentration in the hippocampus might have in the effects of tetanus toxin.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Knowledge-based approach to clinical decision-support system, with an application in tetanus serology.

In tetanus immunization, the need for a booster vaccination can be easily determined by a serological analysis of tetanus antitoxin. Vaccination without knowledge of the immune status carries a high risk of postvaccinal complications. We have used the Pro. M.D. expert system shell to produce the knowledge base TETANUS, to improve the diagnostic interpretation of tetanus antitoxin findings. This knowledge base is comprehensive, runnable, useful, and modifiable by anyone who works with Pro.M.D. and is able to provide medical knowledge in this field.

Antitoxins↗
PubMed1983

Neuronal acquisition of tetanus toxin binding sites: relationship with the last mitotic cycle.

In an earlier study on the developing nervous system, the existence of a temporal correlation between the appearance of tetanus toxin-binding cells and neurogenesis was reported (A. Koulakoff, B. Bizzini, and Y. Berwald-Netter (1982). Dev. Brain Res. 5, 139-147). Using a combined approach of immunocytochemistry and [3H]thymidine autoradiography it is shown that, in the fetal mouse central nervous system, dividing cells do not express membrane binding sites for tetanus toxin. A time-course quantitative autoradiography revealed that the toxin-binding sites become apparent within 7 +/- 1 hr, following the last S phase, on cells undergoing the conversion from dividing to postmitotic state. The acquisition of surface binding sites for tetanus toxin may thus be an early property of nascent central neurons, marking the transition from cycling precursor neuroblasts to postmitotic neuronal cells. Parallel studies on in vivo-developing dorsal root ganglia disclosed that at least some peripheral nervous system cells are endowed with tetanus toxin-binding capacity while still capable of DNA synthesis and undergo one or more divisions.

Animals↗
PubMed1989

Affinity purified tetanus toxin binds to isolated chromaffin granules and inhibits catecholamine release in digitonin-permeabilized chromaffin cells.

Tetanus toxin, a potent neurotoxin which blocks neurotransmitter release in the CNS, also inhibits Ca2+-induced catecholamine release from digitonin-permeabilized, but not from intact bovine chromaffin cells. In searching for intracellular targets for the toxin we studied the binding of affinity-purified tetanus toxin to bovine adrenal chromaffin granules. Tetanus toxin bound in a neuraminidase-sensitive fashion to intact granules and to isolated granule membranes, as assayed biochemically and visualized by electron microscopic techniques. The binding characteristics of the toxin to chromaffin granule membranes are very similar to the binding of tetanus toxin to brain synaptosomal membranes. We suggest that the toxin-binding site is a glycoconjugate of the G1b type (a polysialoganglioside or a glycoprotein-proteoglycan) which is localized on the cytoplasmic face of the granule membrane and might directly be involved in exocytotic membrane fusion.

Adrenal Medulla↗
PubMed1993

Production of biologically active light chain of tetanus toxin in Escherichia coli. Evidence for the importance of the C-terminal 16 amino acids for full biological activity.

The activity of the light (L) chain of tetanus toxin, and of mutants constructed by site-directed mutagenesis, was studied by expression and purification of the proteins from E. coli. Wild-type recombinant L chain (pTet87) was active in the inhibition of exocytosis from cultured bovine adrenal chromaffin cells, although at a level 5-15% of that of L chain purified from tetanus toxin. L chain mutants which terminated at Leu-438 (pTet89), or which contained a Cys-to-Ser mutation at residue 439 (pTet88) were equally as active as the full-length recombinant protein. The reduced activity of pTet87 L chain correlated with C-terminal proteolysis of the protein upon purification. A tryptic fragment derived from native light chain and which terminated at Leu-434 also showed reduced activity in the exocytosis assay, consistent with a requirement of the C-terminal region of the L chain for maximal activity. pTet87 L chain, but neither of the mutants, could be associated with purified H (heavy) chain to form a covalent dimer which induced the symptoms of tetanus in mice. The ability to form biologically active toxin using recombinant L chain will be of great value in structure-function studies of tetanus toxin.

Adrenal Medulla↗