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A M PAPPENHEIMER

Publications and source records attributed to A M PAPPENHEIMER.

At least 37 records · Page 2Linked to original sources

Transfer of delayed hypersensitivity to diphtheria toxin in man.

Simultaneous transfer of delayed hypersensitivity to diphtheria toxin and to tuberculin has been accomplished in eight consecutive instances in man using extracts from washed leucocytes taken from the peripheral blood of tuberculin-positive, Schick-negative donors who were highly sensitive (i.e., pseudoreactors) to purified diphtheria toxin and toxoid. The leucocyte extracts used for transfer contained no detectable antitoxin. The recipient subjects were Schick-positive (<0.001 unit antitoxin per ml. serum) and tuberculin-negative at the time of transfer. All the recipients remained Schick-positive for at least 2 weeks following transfer and in every case their serum contained less than 0.001 units antitoxin at the time when they exhibited maximal skin reactivity to toxoid. Evidence is presented which indicates that the transfer factor may be released from leucocyte suspensions under mild conditions in which most of the cells appear to remain morphologically intact. Four adult Schick-positive subjects have been sensitized to diphtheria toxoid by intradermal injection of a few micrograms of purified toxoid in the form of a washed toxoid-antitoxin precipitate. Two of these sensitized individuals showed severe delayed skin reactions specifically directed against diphtheria toxin (or toxoid) at a time when their serum antitoxin level was less than 0.001 units/ml.

Adult↗

Jaundice in mice due to anomalies of the biliary tract.

There has been described a previously unrecognized disease of mice, characterized by progressive jaundice, first appearing during the nursing period. This has been shown to be due to congenital absence of the terminal segment of the common bile duct, or to the absence of intrahepatic ducts. In the former case, there is distension of the cystic and hepatic ducts, and of the gall bladder, with mucoid material. Biliary cirrhosis and infarct-like areas of necrosis are commonly found in the liver. The cause of the necroses has not been positively determined, but it is suggested that they result from defective arteriolization of the hepatic parenchyma. Inflammatory lesions of the biliary passages, when present, are attributed to secondary bacterial infection. Protozoan-like parasites were present in the gastric epithelium of all mice examined. Their relationship to the biliary and hepatic lesions is as yet undetermined.

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Myocarditis and pulmonary arteritis in mice associated with the presence of rickettsia-like bodies in polymorphonuclear leucocytes.

A previously undescribed disease of mice, characterized by acute interstitial myocarditis, and by periarterial pulmonary lesions, is reported. The transmissibility of this disease has been shown, but a large proportion of inoculated mice appears to be resistant. Microorganisms, rickettsial in form but not positively identified as such, are consistently present in the lesions. They are found predominantly in the cytoplasm of polymorphonuclear leucocytes. Filtrates of fecal material from normal mice of the Harvard breeding stock may produce lesions in myocardium and pulmonary arteries indistinguishable from those occurring in this disease. Rickettsia-like bodies are also found in these lesions.

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Immunochemical studies of antitoxin produced in normal and allergic individuals hyperimmunized with diphtheria toxoid. I. Relationship of skin sensitivity to purified diphtheria toxoid to the presence of circulating, non-precipitating antitoxin.

Among a group of 131 young adults tested, there was a high degree of correlation between the occurrence of immediate skin reactions of the wheal and erythema type produced by purified diphtheria toxoid and personal or familial history of allergy of the hay-fever type. Of 39 Schick-negative subjects who received a "booster" dose of purified diphtheria toxoid, 19 showed no immediate skin reactions before immunization. The development of skin sensitivity in these subjects was associated with the production of non-precipitating circulating antitoxin. Three subjects produced 20 units or more antitoxin per cc. serum following immunization, without demonstrable precipitins. Despite the fact that none showed immediate skin reactions to Schick toxoid prior to immunization, all 3 possessed a high degree of skin sensitivity to toxoid following immunization.

Adult↗

Immunochemical studies of antitoxin produced in normal and allergic individuals hyperimmunized with diphtheria toxoid. II. A comparison between the immunological properties of precipitating and non-precipitating (skin-sensitizing) antitoxins.

1. The immunological properties of two contrasting types of human antisera, each containing a high titer of diphtheria antitoxin, have been investigated. 2. Sera which contain only non-precipitating antitoxin exhibit most of the properties of atopic reagin-containing sera. This type of antitoxin is capable of sensitizing normal human skin to toxin or toxoid and remains for many weeks in the injected area. It exhibits no Danysz effect, does not fix complement unless very large amounts of serum are used, and can be specifically coprecipitated by addition of precipitating antitoxin and toxin. On the other hand, it is capable of sensitizing guinea pigs to fatal anaphylactic shock. Heating at 56 degrees C. for 4 hours destroys the skin-sensitizing properties and results in almost quantitative conversion to a modified antitoxin which is capable of blocking the wheal and erythema reaction caused by injection of toxoid into sensitized skin. Heating at 56 degrees C. does not result in an appreciable loss of neutralizing power as judged by tests in rabbit and human skin. The anaphylactogenic property of nonprecipitating antibody is likewise unaffected by heat at 56 degrees C. 3. Precipitating antitoxin is incapable of sensitizing normal skin to toxin or toxoid and disappears rapidly from the injected sites. It fixes complement to high titer and sensitizes guinea pigs to fatal anaphylactic shock. It was possible to demonstrate inhibition of the wheal and erythema reaction in sensitized skin by injecting certain mixtures of precipitating antitoxin and toxoid. 4. The two antitoxic sera studied in greatest detail represented extreme cases. Many persons immunized with toxoid developed both precipitating and nonprecipitating antitoxin simultaneously.

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Observations on encephalomyelitis of mice (DA strain).

A new agent, DA, has been isolated from a spontaneously paralyzed mouse. Its biological properties and the pathology of lesions in experimental infection indicate close relationship with the Theiler group of encephalomyelitis viruses. Serological studies were inconclusive. The intracerebral neutralization test failed to reveal measurable antibody and other routes of inoculation were unsuitable because of low invasiveness of the agent. Repeated vaccination of females did not render their offspring resistant to homologous intracerebral challenge. The occurrence of early viremia is reported following intracerebral inoculation of the DA strain and also the known Theiler strains, 4727, FA, and GD-VII. The pathology of mice experimentally infected with DA and with known members of the Theiler group is described. Attention is called to the demyelinating lesion of the cord in mice surviving for several months and to the persistence of virus in the CNS of such animals. Another characteristic feature of the pathology was the degeneration of ventral nerve roots and in some mice of the peripheral nerves. Similar changes were not seen with strains of Theiler virus other than DA. Spheroidal bodies of undetermined significance were found in the lesions. Finally the occurrence of myositis after intracerebral inoculation, not only mice infected with the DA virus, but also with the 4727 and FA strains, is described and discussed.

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The effects of diphtheria toxin on the Cecropia silkworm.

1. The metamorphosis of the Cecropia silkworm is accompanied by large and systematic changes in the insect's sensitivity to diphtheria toxin. 2. Injection of less than 1 gamma of toxin into mature caterpillars, prepupae, or developing adults causes cessation of development followed by delayed death 1 to 5 weeks later. 3. Dormant pupae, on the contrary, are resistant to 70 gamma of toxin and may survive even this enormous dose for over 4 weeks. One-hundredth of this dose, however, prevents pupae from initiating adult development. 4. Tetanus toxin, to which the insect is insensitive, failed to duplicate any of these effects. 5. Maximal sensitivity to diphtheria toxin is characteristic of those stages in the life history which depend on the presence and function of the cytochrome system. Resistance to the toxin, as in the case of the diapausing pupa, is correlated with the existence and utilization of metabolic pathways other than the usual cytochrome system. 6. This correlation persists within the individual insect. Thus, within the diapausing pupa, the toxin fails to affect the heart in which a normal cytochrome system is absent, but, within the same insect, causes a degeneration of the intersegmental muscles in which an intact cytochrome system is present. 7. These several lines of evidence are interpreted in support of the conclusion that diphtheria toxin acts by blocking the synthesis of one or more components in the cytochrome system.

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