Robert A. Cooke

Experimental toxic and allergic contact dermatitis. II. A histopathologic study.

Abstract Chronologic development of histologic changes at the site of allergic and toxic dermatitis is described in detail. Mononuclear cell invasion, vacuolization, vesicle formation, and exfoliation of the epidermis are steps in a process characteristic of the allergic response. A comparison of the histologic and chemical changes in toxic and allergic dermatitis indicates that sensitization induced a capacity in the mononuclear cells for positive chemotaxis, for induction of characteristic inflammatory changes, and for participation in metabolic processes (presumably by increased enzymatic activity). A sensitization of epidermal cells has not been ruled out. An extreme acanthosis seen in allergic lesions of animals treated with germanin might be regarded as the allergic response of epidermal cells after participation of mononuclear cells has been forestalled.

Experimental and clinical study of fresh and modified pollen extracts

Abstract 1.1. Fresh extracts of pollen were modified by formolization, radiation with ultraviolet light, heating, acctylation, and alum-precipitation and were compared in clinical and experimental studies with fresh and regular extracts. 2.2. Treatment of undialyzed extracts of pollen with formaldehyde resulted in an increase in nitrogen precipitated with protein by phosphotungstic acid. It was shown that after formaldehyde treatment part of the dialyzable nonprotein nitrogen was precipitated with protein, and experiments suggested that protein split products, such as amino acids, might be precipitated under such conditions.Heating to 70° C. caused a precipitation and loss of protein nitrogen in ragweed extracts, but none in timothy extract. 3.3. The protein in pollen extracts was stabilized by treatment with formaldehyde, heating, or radiation with ultraviolet light. In alumprecipitated ragweed extract there was a loss of protein on ageing, similar to the loss in regular extract. 4.4. The gelatin liquefying enzymes in ragweed pollen extract were inactivated by formolization, heating to 70° C. for an hour, acetylation or radiation with ultraviolet light, and subsequent heating to 40° C. 5.5. In neutralization of sensitive serum, the extracts modified by formolization, heating, radiation with ultraviolet light, and acetylation were reduced in activity in comparison with fresh extract. Regular extract one year old showed a loss of neutralizing capacity out of proportion to the decrease of protein content. 6.6. The serologic response in hay fever patients treated with acetylated, formolized, and heated extract was less than that in patients treated with regular, fresh, or alum-precipitated extracts. The fresh extract gave the greatest response. 7.7. Modification of the pollen extracts did not eliminate constitutional reactions. Since the various phenomena produced by the modified extracts required different degrees of specificity, no single test could be considered a measure of all types of allergic activity. 8.8. The clinical results were best in the group of hay fever patients treated with fresh extract. Alum-precipitated and formolized extracts gave results which seemed fairly comparable to those obtained by regular extract. Heated and acetylated extracts gave the least satisfactory results. 9.9. The antigenic relationship of the fresh, formolized, and heated extracts was studied by means of the Dale test. The formolized and heated extracts showed a modification of specificity in that they failed to neutralize uteri of pigs sensitized with regular extract.

The sensitivity of man to human dander, with particular reference to eczema (allergic dermatitis)

Abstract 1.1. Human dander extract was found to be reactive in certain human skins. 2.2. Thirty of thirty-three patients with eczema were skin reactive to human dander extract, and their sera contained skin-sensitizing antibodies for it. 3.3. The results of direct skin tests on various allergic and normal persons are given. Cases of eczema usually showed positive reactions, while the noneczema persons usually showed negative reactions. 4.4. Only ten of ninety sera from patients with allergic diseases other than eczema contained skin-sensitizing antibodies. None of ten normal nonallergic sera contained skin-sensitizing antibodies. 5.5. Only three of seventy-five patients with dermatoses other than eczema were significantly reactive to human dander extract. 6.6. The quantitative studies of the human dander antibody by means of dilution tests are given. 7.7. Neutralization tests of human dander-sensitive sera, with human dander antigen and house dust antigen are described. 8.8. No relationship was found between sensitivity to human dander and that to other animal danders.

Study on the mechanism of dermatitis venenata in the guinea pig with a demonstration of skin-sensitizing antibody by passive transfer.

Abstract 1.1. Guinea pigs were sensitized to poison ivy extract by cutaneous application of the antigen. 2.2. Successful passive transfer of dermatitic sensitivity was obtained in seven of fifteen trials with serum and sixteen of nineteen trials with a suspension of splenic cells. Reactions caused by serum were slight. 3.3. The dermatitic antibody could be demonstrated in saline extracts of washed splenic cells. 4.4. The dermatitic antibody did not pass through the placenta.

Preliminary evaluation of a new corticosteroid in allergic diseases

Abstract Sixteen patients with bronchial asthma and one with perennial rhinitis were treated for four to eleven weeks with triamcinolone. The compound was demonstrated to have a potent therapcutic effect about twice that of prednisone or prednisolone, on a weight basis. There was improved appetite in three patients, and decreased blood pressure was noted in twelve patients.

Passive cutaneous anaphylaxis (PCA) in the guinea pig: An immunologic and pathologic study

Abstract 1.1. In view of present experiments, the immunologic property of antisera to induce passive cutaneous sensitization to guinea pig skin is attributed to the guinea pig smooth-muscle-sensitizing antibody, not conditioned by presence of precipitins. The human-skin-sensitizing antisera property (of human or animal origin) is neither related to the muscle-sensitizing property nor responsible for the induction of passive sensitization of guinea pig skin (PCA). 2.2. The fixation of antibody responsible for passive cutaneous reactivity is dependent upon competitive fixation of reactive antibody gamma globulin and serum gamma globulin. The ratio of antibody to serum globulin seems to determine the degree of saturation of the skin receptors with reactive and nonreactive gamma globulin. 3.3. The efficacy of antihistamine, heparin, and hydrocortisone to inhibit passive cutaneous anaphylaxis in guinea pig is limited. Administration of increased doses does not promote increased inhibition. Nontoxic doses of adrenaline are the most effective. The vasoconstricting effect of adrenaline appears to emphasize the vasodilation as an important partial mechanism in passive cutaneous anaphylaxis. 4.4. Passive cutaneous anaphylaxis in the guinea pig is a manifestation of an interaction between a passively fixed antibody and circulating antigen simultaneously at all points of sensitivity. It is a vascular phenomenon with dominant venous and capillary manifestations, rather than an arteriolar response as in Arthus phenomena. This is evidenced by the macroscopic observations and the microscopic findings in passive cutaneous anaphylaxis.

The association with pseudoglobulin of the skin sensitizing substance of allergic (hay fever) serum

Abstract 1. The skin sensitizing substance from allergic serums was associated specifically with the pseudoglobulin. 2. There was indication that treatment of patients with pollen extract caused a qualitative alteration in their serum pseudoglobulin rather than a significant quantitative change.

Experimental toxic and allergic contact dermatitis: I. A chemical study of histamine content

Abstract 1.1. Histamine determinations at the sites of allergic dermatitis and toxic dermatitis demonstrate that excessively high levels of histamine are specifically associated with the allergic response (contact dermatitis) but not with the primary inflammatory response (toxic dermatitis). 2.2. The histamine increase in toxic dermatitis is attributed to the number of infiltrating cells, whereas it is assumed that the excessive histamine accumulation in allergic dermatitis is due to the capacity of the infiltrating mononuclears, upon minute stimulation with antigen, to activate the histamine metabolism. The latter assumption is supported by the result of an experiment with germanin, an inhibitor of decarboxylation of l-histidine into histamine. 3.3. The role of histamine in the allergic dermatitis seems to be that of an accelerator of the repair process rather than of a causal factor.

A study of leukocytic antibodies in allergic patients

Abstract 1.1. Delayed type skin sensitivity to tuberculin was transferred to tuberculin-negative human recipients by means of leukocytic extracts and disrupted leukocytes obtained from the peripheral blood of tuberculin-sensitive human donors. 2.2. Attempts to transfer immediate type skin sensitivity to ragweed pollen, penicillin, and horse serum from human donors to human recipients, by means of leukocytic extracts or disrupted leukocytes, were unsuccessful. Negative results were also obtained with viable leukocytes from ragweed-sensitive patients. 3.3. Leukocytic extracts and disrupted leukocytes obtained from patients sensitive to both tuberculin and ragweed, or to tuberculin and penicillin, are capable of transferring delayed type sensitivity to tuberculin but not immediate type sensitivity to ragweed pollen or penicillin. 4.4. From these findings, we have concluded that leukocytes derived from the peripheral blood of specifically sensitive human donors (a) contain an unknown substance responsible for the transfer of tuberculin sensitivity and (b) do not contain skin-sensitizing antibody against ragweed pollen, penicillin, or horse serum which can be detected on passive transfer. 5.5. Leukocytic extracts from patients sensitive to horse serum or to ragweed pollen did not contain precipitins or anaphylactic shock-producing antibodies against horse serum or ragweed pollen extract, respectively.

Antigenic studies by the dale test: I. The antigenic relationship of certain pollens

Abstract 1.1. The protein fraction of low ragweed pollen extract produced muscular contraction and completely neutralized the uterine antibodies of guinea pigs sensitized by whole low ragweed pollen extract, as evidenced by the Dale test. Whereas, dialyzed low ragweed pollen extract also produced muscular contraction and neutralized the uterine antibodies to the whole extract, the dialysate completely failed to cause any contraction. The standardization of whole pollen extracts on the basis of their protein content was a measure of the reactive substance in whole pollen extract. 2.2. Specific pollen extract always neutralized to the related pollen extract. 3.3. A related pollen extract in every instance produced a contraction of the uterine horn sensitized by a specific pollen. 4.4. The related pollen extract neutralized to the specific in 21 instances and did not neutralize in 17 experiments. 5.5. These experiments indicate an antigenic relationship but not an identity of the pollens used in this study.