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PubMed1978

[Study of the chemical receptor for diphtheria toxin in cell membranes].

Adsorption of diphtheria toxin on immobilized cell membrane preparations in the presence of gangliosides was studied. A mixture of gangliosides completely inhibited the adsorption of diphtheria toxin on the cell membranes, both sensitive (HeLa cells, macrophages) and resistant (L-cells) to its action. Neuraminidase-treated gangliosides were less effective. Immobilized gangliosides adsorbed diphtheria toxin effectively in the presence of a protective colloid and detergent triton X-100. The results obtained suggest gangliosides to be diphtheria toxin receptors.

Adsorption↗
PubMed1982

Entry of the toxic proteins abrin, modeccin, ricin, and diphtheria toxin into cells. I. Requirement for calcium.

In the absence of Ca2+ cells were not sensitive to the toxic proteins abrin and modeccin and the sensitivity to ricin and diphtheria toxin was reduced. Calcium deprivation had little effect on the binding and endocytosis of abrin, modeccin, and ricin. The binding of diphtheria toxin to cells was, however, reduced, Verapamil and Co2+ inhibited 45Ca2+ uptake and protected cells against abrin and modeccin at low concentrations of Ca2+. At higher Ca2+ concentrations the protection was overcome. La3+ inhibited strongly 45Ca2+ uptake and protected well against all four toxins, even at high Ca2+ concentrations. Fe3+ also afforded protection although it did not inhibit Ca2+ uptake. The Ca2+ ionophore, A23187, which strongly increases the uptake of 45Ca2+, protected cells well against abrin and modeccin, slightly against diphtheria toxin, but not against ricin. Both Ca2+ deprivation and treatment with A23187 protected well against the hybrid toxin abrin A-chain/ricin B-chain. Such treatment afforded little protection against the hybrid ricin A-chain/abrin B-chain. Apparently the protection against abrin is associated with its A-chain. The calmodulin inhibitor, trifluoperazine, protected strongly against modeccin and diphtheria toxin. The data indicate that Ca2+ is involved in the entry mechanism for abrin, modeccin, and ricin, possibly as a Ca2+ flux together with the toxins.

Abrin↗
PubMed1978

Diphtheria and tetanus antitoxin levels in Thai children.

Determination of diphtheria and tetanus antitoxin levels by an indirect haemagglutination method were conducted in 101 nonimmunized schoolchildren, 155 pediatric patients and 102 blood donors. Diphtheria and tetanus antitoxin levels were found mostly adequate among immunized children. Diphtheria antitoxin levels were found adequate in 68.3% of the non-immunized schoolchildren. Tetanus antitoxin levels were found inadequate for protection in the non-immunized children and adults. Immunization of children and adults with diphtheria and tetanus toxoid are highly recommended.

Adult↗
PubMed1981

Kinetics of protein synthesis inactivation by diphtheria toxin in toxin-resistant L cells. Evidence for a low efficiency receptor-mediated transport system.

In an attempt to gain an understanding of the mechanism by which toxins enter cells, we have analyzed the intoxication of diphtheria toxin in the toxin-resistant L cell and compared these results with those previously reported for toxin-sensitive HeLa and KB cells (Uchida, T., Pappenheimer, A. M., Jr., and Harper, A. A. (1973) J. Biol. Chem. 248, 3845-3850; Moehring, J. M., and Moehring, T. J. (1976) Infect. Immun. 13, 221-228). The inactivation of protein synthesis in diphtheria toxin-treated L cells is characterized by first order inactivation kinetics and a concentration-dependent lag phase. The log rate of inactivation of protein synthesis when plotted versus toxin concentration yields a complex hyperbola with a saturable component detected in the range of 5 to 10 X 10(-5) M. We conclude that the intoxication of L cells by diphtheria toxin in the range of 10(-8) to 5 X 10(-6) M occurs via a saturable process and that the saturable component probably represents a plasma membrane toxin receptor with an affinity 200-fold lower than that found in sensitive HeLa cells. Since L cells require a 10(4)- to 10(5)-fold higher toxin dose than HeLa cells, a 200-fold affinity difference cannot fully explain the resistance of L cells to diphtheria toxin. In addition, L cells must have either fewer toxin receptors or a deficiency in the transport step(s). Because toxin-exposed L cells in contrast to sensitive cells exhibit different behavior with respect to pH and pH reversal of NH4Cl protection, a deficiency in the transport step is considered the more likely case.

Ammonium Chloride↗
PubMed1980

The dose of diphtheria toxoid in combined vaccines and their use in children.

The currently recommended immunization scheme consists of diphtheria, tetanus and pertussis vaccine (DTP) given at the ages of 3, 4 1/2 and 6 months, followed by a reinforcing dose of the same vaccine at 18 months, and one of diphtheria and tetanus vaccine (DT) before school entry. Children injected according to this scheme may be over-immunized. The amount of diphtheria toxoid (25 Lf per dose) contained in DTP should not be reduced, because some of the children missing the third primary dose would be left unprotected until after the 18-month injection had been given. It is likely that the 18-month dose could be omitted without great danger if the preschool booster dose were assured, and more than likely that preschool boosting with DT is unnecessary if the full course, including the 18-month dose, has been given. Reinforcing doses of tetanus toxoid need not be given as often as every 10 years. They are probably not required except in the case of injury and may, even then, be omitted if less than 5 years have lapsed since the completion of basic immunization, or since the injection of the last booster dose. Non-adsorbed diphtheria and tetanus toxoids may be the preparations of choice whenever immunity has to be reinforced.

Child↗
PubMed1980

Tetanus and diphtheria immune status of patients in a family practice.

Sera obtained randomly from 37 patients seen at a family practice center were evaluated for protective antibodies against tetanus and diphtheria using in vivo toxin neutralization methods. The patients' ages ranged from 1 to 99 years. Seventy-four percent and 83 percent of patients were found to have protective antitoxin titers against tetanus and diphtheria, respectively. No significant differences in immune status were detected among different sexes or races. Whereas the mean age of subjects susceptible to tetanus was significantly greater than for those with protective antibody levels, this was not the case with diphtheria. It is postulated that natural diphtheria infection may be responsible for the high degree of protection noted among older subjects surveyed. Practical as well as educational benefits that may be obtained from a study of this nature are discussed.

Adolescent↗
PubMed1981

Methylamine stimulates the action of ricin toxin but inhibits that of diphtheria toxin.

The action of ricin toxin was stimulated by addition of methylamine or some other amines, as shown by measuring the inhibition of protein synthesis of cultured cells by the toxin. Under the same conditions, however, the action of diphtheria toxin was completely inhibited by the amines. In a cell-free protein-synthesizing system, methylamine had no effect on the action of the A chain of ricin toxin and fragment A of diphtheria toxin. Studies on the interactions of 125I-labeled toxins with cells revealed that methylamine did not alter toxin-receptor bindings, but affected the entry of the toxins into the cells. Studies were also made on the effects of methylamine on the actions of two hybrid toxins, formed from a subunit of Wistaria floribunda lectin and fragment A of diphtheria toxin and the A chain of ricin toxin, respectively. Results suggested that the processes of entry of ricin toxin and diphtheria toxin, or at least parts of these processes, are different.

Cell-Free System↗
PubMedDate not supplied

[Diagnosis of pharyngeal and laryngeal diphtheria in adults].

142 adults with pharyngeal and laryngeal diphtheria were registered in Yekaterinburg in 1993. Of them, 136 patients recovered and 6 died. The analysis of the clinical features and diagnostic errors showed that subjects with chronic visceral diseases and alcoholics are more likely to have poor prognosis of diphtheria. Diphtheria manifested primarily with edema followed by infiltration of the mucosa, with appearance of thin transparent furs, tenderness of cervical regional lymph nodes. The typical greyish-brown thick and firm false membranes occurred only in the late stage of the disease. The features of the diphtheric croup in the adults complicated the diagnosis. These were, unlike croup in children, the vagueness of the stages of this syndrome, rapid involvement of the trachea and bronchi, mixed type of dispnea and delirious state in alcoholics. It is necessary to set up the duty of ENT specialists in the diagnostic departments of the infectious hospitals for repeated endoscopic and bacteriologic examinations of the diphtheria suspects.

Adult↗
PubMedDate not supplied

[The local manifestations of diphtheria].

The development of diphtheria is characterized by a pronounced local process, but the description of local changes in the disease are based only on postmortem findings. 67 patients with different forms of diphtheria were examined. In 11 cases of descending croup bronchoscopic examination was carried out. As revealed in this study, at the primary stage of the disease films cover the whole of the air duct system, and the process is identical to that on tonsils. In the course of convalescence and under the action of specific antiserum films on the tonsils, the soft palate and the vocal cords disappeared, and films in the larynx, the trachea and bronchi could be easily separated from the mucous membrane, but always with the formation of erosions and even perforations in it. The character of the process was indicative of the absence of any specific action of diphtheria toxin on the mucous membrane at the site of the inoculation of the infective agent. No correlation between the severity of the course of diphtheria, the degree of edema and the frequency of the development of complications was noted.

Adolescent↗
PubMed1994

[Endocarditis due to Corynebacterium diphtheriae cause by contact with intravenous drugs: report of 5 cases].

The clinical features of 5 patients with invasive disease due to nontoxigenic Corynebacterium diphtheriae are presented. 4 patients had proven left sided endocarditis, and one had probable endocarditis of the mitral valve. 4 patients were intravenous drug abusers, and one had a girl friend who was also an iv-drug abuser. Only one patient had antibodies against human immunodeficiency virus. 2 patients with endocarditis of the mitral or the aortic valve, and one patient with endocarditis of a prosthetic aortic valve, died of septic complications. All patients or their partners frequented the same community of drug abusers. Since the blood culture isolates shared common features for biotyping, resistance patterns and also for ribotyping in three tested patients, we assume that all patients were infected by the same clone of C. diphtheriae. Drug abusers may become a new reservoir for C. diphtheriae infection. Along with our patients, we present an overview of the 49 published cases of C. diphtheriae endocarditis.

Adult↗
PubMed1993

[Diphtheria--new threat or traditional disease].

Clinical and epidemiological data of the diphtheria have been described on the basis of literature findings and own observations. It have been introduced the informations presented during Meeting on Diphtheria Epidemic in Europe, Saint Petersburg, 1993. I have concentrated on the some differences between diphtheria in nowadays and in previous years and offer some suggestions concerning the treatment of this disease. It concern also plasmapheresis as a special effective procedure in toxic forms of the diphtheria.

Adult↗
PubMed1995

[The protective effect of the nerve growth factor on sensory neurons in organotypic culture under the action of diphtheria toxin].

Diphtheria toxin (1.10(-1) - 1.10(-6) Lf/ml) was found to inhibit neurite extension in chick embryo dorsal root ganglia in vitro. If the nerve growth factor (60 ng/ml) was added with the toxin to culture media, the effect of diphtheria toxin was seen to decrease and the neurite outgrowth was compared with control. Protective effect of nerve growth factor estimated by the influence of diphtheria toxin may be used for new principles of diphtheria treatment.

Animals↗
PubMed1995

Immunity to diphtheria in children three-to-six year of age in four counties of Taiwan.

An immunization program against diphtheria has been implemented in Taiwan since 1955, using combined diphtheria, pertussis and tetanus (DPT) vaccine. Diphtheria immunoglobulin (DIG) level was assessed in serum samples obtained from 1138 children, aged 3-6 years from north, south, east and central part of Taiwan by the VERO cell neutralization method. Specimens were collected by simple random sampling of residents from Hsinchu, Taichung, Pingtung and Hwalien counties, including both aborigines and non-aborigines. The former lived in one or two villages in each county, and the latter lived in a single village next to the former. Ninety-five percent (1086/1138) had a DIG titre > or = 0.01 IU/ml. There was no significant difference by sex, or by residential area. Seventy-nine percent (901/1138) of the children had completed the primary immunization schedule (at the age of 2, 4, 6 and 18 months), and the prevalence of DIG titre > or = 0.1 IU/ml considered to be long-term protective was as follows: 74.6% for 3-year group; 74.5% for 4-year group; 67.9% for 5-year group; 84.7% for 6-year group (including 52.2% who had had a booster shot at early primary school). These findings show that the diphtheria vaccination program provides good immunity in childhood.

Animals↗
PubMedDate not supplied

[The status of the immunity system in diphtheria].

The complex study of cell-mediated and humoral immunity characteristics, as well as nonspecific protective factors, in 30 diphtheria patients, 9 clinically healthy carriers and 54 healthy subjects was carried out. In healthy immunized subjects normal characteristics of all elements of immunity were observed in combination with high titers of antitoxins and sensitization of lymphocytes to diphtheria toxoid. In healthy carriers the presence of cell-mediated and humoral immunity to diphtheria was associated with disturbances of the metabolic activity of phagocytes and a decrease in the proliferation of lymphocytes in response to the mitogen. Diphtheria patients were found to have changes in all elements of immunity, especially pronounced in severe forms of the disease.

Adolescent↗
PubMed1998

[The protective effect of the nerve growth factor in exposing a nerve tissue culture to diphtheria toxin].

Diphtheria toxin (1.10(-1)-1.10(-6) Lf/ml) was found to inhibit neurite extension in chick embryo dorsal root ganglia in vitro. If the nerve growth factor (60 ng/ml) was added with toxin in culture media the diphtheria toxin effect was decreased and the neurite outgrowth was compared with control. Protective effect of nerve growth factor by influence of diphtheria toxin may be used in new principles of diphtheria treatment.

Animals↗
PubMed1992

[Diphtheria immunity in school beginners and after reimmunization with d-vaccine].

The antitoxin immune status against diphtheria was determined in 814 children, aged 6-7 years, 5-6 years after first immunization. All children were then re-immunized with d-vaccine. 4-8 weeks later antitoxin was again measured to assess the immunogenic effect of the booster injection (reduced toxoid dosage of 5 IU/0.5 ml). Although all children had been completely immunized as infants, 149 of them (18.3%) presented inadequate or no immunity to diphtheria. The booster injection resulted in a reliably protective antibody concentration of 0.1 IU/ml serum even in children with low or no longer demonstrable residual immunity. The high proportion of inadequately protected children and the further continual loss of antitoxin antibodies makes booster injection mandatory at the time of beginning school as well as in juveniles and adults. The Standing Immunization Commission of the Federal German Health Office recommends this re-immunization every 10 years in the form of combined tetanus-diphtheria immunization with Td vaccine.

Child↗
PubMedDate not supplied

[Specific features of diphtheria vaccinal process in children with rheumatic diseases].

Clinical and immunological examination of 55 children aged 6-15 years with rheumatic diseases, immunized against diphtheria, was carried out. All children were immunized at the stage of clinical and laboratory remission and in some cases while undergoing a prolonged course of cytostatic therapy or therapy with nonsteroid anti-inflammatory remedies. This examination demonstrated that in the overwhelming majority of children with rheumatic diseases the diphtheria vaccinal process took an asymptomatic course and had no influence on the course of the main disease. Specific features, characteristic of the immune status of this group of children, were established. In the course of the vaccinal process the restoration of the initially inhibited characteristics (the production of TNF-alpha and IL-2) to normal values were shown to occur, which was indicative of the fact that the reserve capacities of immunocompetent cells were retained in these patients. This study also revealed that immunization of children with rheumatic diseases with adsorbed DT and D toxoids with reduced antigen content was not excessive antigenic stimulation for such children, as it did not lead to immunopathological shifts, but induced transient phase changes in immunological characteristics, similar to those in healthy children. Protective levels of antibodies to diphtheria were shown to retain for a long time with considerable prolongation of intervals between booster injections. The simultaneous course of immunosuppressive maintenance therapy in the average dosage used for the corresponding age group did not inhibit the production of protective antibodies.

Adolescent↗
PubMed1977

Pathogenesis of diphtheria carrier state from the immunological point of view.

Results of a comparative investigation of diphtheria antitoxin and type-specific antibacterial antibodes in 264 carriers of diphtherial bacteria, 41 diphtheria patients and 263 non-infected subjects are presented. A high level of antitoxin did not prevent the development of toxigenic-strain carrier state. A basically similar immunological antibacterial response was observed in patients with manifest forms of diphtheria and in carriers of toxigenic strains; such a response could not as yet be detected in carriers of non-toxigenic strains. It has been suggested that the infectious process in the toxigenic-strain carrier state is due to factors of the virulence responsible for infectivity and invasiveness of the diphtherial microbe. The toxin plays no pathogenic role in carrier state.

Adolescent↗