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J W UHR

Publications and source records attributed to J W UHR.

16 recordsLinked to original sources

The effect of bacterial endotoxin on the newborn guinea pig.

Newborn guinea pigs (less than 24 hours old) are highly susceptible to the lethal effect of endotoxin and susceptibility decreases with age. The vulnerability to endotoxin has not been attributed to hypofunction of either the adrenal gland or the reticuloendothelial system of the newborn, since prior injection of corticosteroids provides only partial protection to endotoxin and newborn guinea pigs can efficiently remove colloidal substances from the circulation. In contrast to adults, newborns do not develop a delayed inflammatory reaction following intradermal injection of endotoxin, and after intravenous challenge frequently fail to display neutropenia and sustained fever.

Antitoxins↗

Antibody formation. III. The primary and secondary antibody response to bacteriophage phi X 174 in guinea pigs.

Injection of a small bacteriophage phiX 174 into guinea pigs results in an accelerated elimination of phage detectable as early as 24 hours after injection. The immune nature of the accelerated elimination is indicated by its specificity, by the appearance of excess specific serum antibody after phage elimination, and by the prevention of accelerated elimination by 400 r whole body x-irradiation of guinea pigs prior to injection of phage. The early antibody response is considered to be a primary one since an analogous response occurs in newborn guinea pigs, antibody is not detectable in the sera of non-immunized animals, and the second challenge with phiX stimulates a serum antibody response 100-fold greater than that after primary immunization. The early detection of immune elimination appears to be due, in part, to the small amounts of phage employed, since larger doses of phage delay the time of onset of detectable immune elimination. The early rise of serum antibody in the primary and secondary response appears exponential with a similar rate constant of antibody formation. The rate constant is also independent of dose. These findings have led to the suggestion that during this exponential phase, the relative rate of antibody formation at a cellular level may be constant for a given antigen.

Animals↗

Antibody formation. I. The suppression of antibody formation by passively administered antibody.

The suppression of antibody formation by passively administered antibody is influenced by the dose and nature of the antigen, type of immunization procedure, ratio of antibody to antigen, species origin and characteristics of the antiserum used, as well as the species selected for immunization. In guinea pigs, diphtheria antitoxin formation can be effectively suppressed by an intravenous injection of excess homologous or heterologous antitoxin as long as 5 days after toxoid immunization and after delayed-type hypersensitivity to toxoid has developed. Following the period of antibody suppression which lasts 2 to 7 weeks, serum antibody can usually be demonstrated. It is proposed that this delayed immunization results from dissociation of antigen, since diphtheritic paralysis and death can be produced in guinea pigs and rabbits by the intravenous injection of toxin-antitoxin precipitates formed in antitoxin excess. This syndrome is prevented by injection of excess horse antitoxin 1 hour after injection of the toxin-antitoxin complexes.

Animals↗

Antibody formation. II. The specific anamnestic antibody response.

Diphtheria toxoid-antitoxin precipitates formed in antitoxin excess can prepare guinea pigs, rats, and rabbits for a secondary type of antitoxin response. Priming may occur without the development of detectable serum antibody. In rats, toxoid-antitoxin precipitates are more efficient than "free" toxoid in priming, whereas in guinea pigs, the magnitude of the anamnestic response varies with the precipitate employed. The possibility that priming is due to "free" antigen released from the specific precipitate rather than the precipitate itself is discussed. The anamnestic antitoxin response can be inhibited by passive antitoxin, but less efficiently than primary antitoxin formation. Partial suppression of the secondary antitoxin response was accomplished by injection of excess horse antitoxin as long as 4 days after reimmunization with toxoid. The importance of these findings for the understanding of passive-active immunization in the human is discussed.

Animals↗

Delayed hypersensitivity. III. Specific desensitization of guinea pigs sensitized to protein antigens.

Guinea pigs rendered hypersensitive (delayed-type) to protein antigen can be completely and specifically desensitized by a single injection containing a sufficient amount of the corresponding antigen. Although 1 to 2 mg. of specific antigen are required for complete desensitization, as little as 20 microg. suffices to decrease the size of specific skin reactions in sensitized animals. The duration of non-reactivity lengthens as the amount of antigen in the desensitizing injection is increased, but skin reactivity eventually returns and is accompanied by the appearance of excess circulating antibody. Desensitization can be accomplished with the antigen-antibody complex as well as by "free" antigen. The appearance of delayed skin reactions can be prevented in fully sensitized animals by intravenous desensitization 2 or more hours after intradermal challenge or by simply skin testing with a desensitizing dose of specific antigen. Injection of a desensitizing dose of antigen into specifically sensitized animals also results in a transient anergic state, the implications of which are discussed.

Allergens↗

Delayed hypersensitivity. IV. Systemic reactivity of guinea pigs sensitized to protein antigens.

Guinea pigs with delayed hypersensitivity to protein antigens show a specific febrile response accompanied by a lymphopenia following injection of a desensitizing dose of specific antigen. No signs of shock are observed in highly sensitive animals following this injection. The response is not prevented in sensitive guinea pigs by inducing endotoxin tolerance or by pretreating with cortisone before specific challenge. Using a suitable antigen in sufficiently sensitive animals as little as 100 microg. can elicit a pronounced febrile response. Injection of a desensitizing dose of antigen specifically abolishes systemic as well as skin reactivity for several days. Normal or hypersensitive (delayed-type) animals passively sensitized with sufficient amounts of serum antibody show hypothermia after specific challenge and may show a delayed type of fatal shock. Differences were noted between their systemic reactivities, however, and the reactivity seen in specifically challenged tuberculous animals.

Allergens↗

Delayed hypersensitivity. I. Induction of hypersensitivity to diphtheria toxin in guinea pigs by infection with Corynebacterium diphtheriae.

Guinea pigs infected by intradermal injection of living toxigenic diphtheria bacilli and protected by horse antitoxic globulin, given either before or after infection, develop delayed hypersensitivity of the tuberculin type to diphtherial proteins. The highest degree of hypersensitivity is specifically directed against diphtheria toxin (or toxoid) itself, although smaller delayed skin reactions may be evoked in sensitized animals by other diphtherial proteins common to both toxigenic and non-toxigenic strains. Animals sensitized to diphtheria toxin by infection with a toxigenic strain in this way react positively to the Schick test and their serum usually contains no detectable antitoxin 2 to 3 weeks after the initial infection. Animals infected with living non-toxigenic diphtheria bacilli become sensitized to proteins common to both toxigenic and non-toxigenic strains but do not show sensitivity to toxin. The observations suggest that a minute amount of toxoid, or of toxin comparable to that which might be liberated during infection, might induce the hypersensitive state if injected in the form of a complex with excess antitoxin. This prediction is verified by the results reported in the following paper (23).

Animals↗

Delayed hypersensitivity. II. Induction of hypersensitivity in guinea pigs by means of antigen-antibody complexes.

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed.

Animals↗

Chylothorax.

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Chylothorax↗