Hugh Zachariae

HISTAMINE AND MAST CELLS IN HUMAN FETAL SKIN.

Summary Histamine and mast cells were studied in human fetal skin. Skin histamine rose with increasing fetal age. The appearance of identifiable mast cells coincided with the presence of larger amounts of cell-bound histamine in skin. The investigations also demonstrated a high ratio of wet weight to dry defatted weight, which declined with increasing fetal age. This is in agreement with the observation that tissue edema invariably initiates processes of connective-tissue growth, repair, and regeneration. It is proposed that, in early fetal life characterized by rapid growth, the demand for histamine is so considerable that storage of cell-bound histamine in skin cannot take place. The author is indebted to the Laboratory for Fetal Research (Head: Dr. Henning Andersen, Childrens Dept., Univ. Hasp, of Copenhagen) supported by the Association for the Aid of Crippled Children, New York, and Dr. Helge Andersen, Univ. Inst. of Medical Anatomy, Copenhagen, for assistance in obtaining specimens used in these studies.

Kinin Formation and Inactivation by Alcalase, a Proteolytic Enzyme

Summary Incubations of human plasma and synthetic bradykinin with the proteolytic enzyme Alcalase demonstrated kinin forming and kinin-destroying properties of this product. Kinin formation by Alcalase was inhibited by Trasylol.

HISTAMINE IN FULL-THICKNESS SKIN AUTOGRAFTS OF RAT.

Summary Analyses of histamine and water content performed on full thickness auto-grafts of rat skin showed a considerable histamine release during the first 24 hours after operation. Simultaneously an increase in water content of the graft was measured. It is suggested that histamine may play a role in the early phase of repair and to survival of the graft, presumably by increasing vascular permeability.

BRADYKININ INDUCED EOSINOPHILIA IN “SKIN WINDOWS”

Several lines of evidence indicate that kinin peptides participate in the inflammatory process (3, 7) . Injected into tissue, bradykinin produces vasodilatation, increased vascular permeability, smooth muscle stimulation, and pain. The cellular response to bradykinin has been studied in tissue sections ( i ) . With large doses there is attraction of leukocytes to the injected site. According to Archer ( i ) bradykinin has not been found chemotactic for eosinophils. In previous studies on skin windows (6) two of us found that histamine and histamine liberators gave rise to eosinophilia. The present paper describes the cellular response to bradykinin, as demonstrated by the skin window technique (5).

Comparison of the antiwealing effect of the antiamines BP 400 and cyproheptadine and an antihistamine HS 592.

Observations on skin histamine suggest that histamine plays a part in a number of skin diseases ot inflammatory or allergic nature (5) . Histamine, however, is no longer considered the only chemical mediator in these conditions. Serotonin, although probahly of greater importance in the rat than in man, and kinin peptides may also contribute (2, 6) . Antiamine is a new term characterising drugs which possess not only antihistaminic properties but also antagonize other biogenic amines and possibly also kinin peptides such as bradykinin. The present study offers a comparison of the effect of two antiamines, BP 400 and cyproheptadine, as well as the effect of a new antihistamine drug HS 592, on histamine, serotonin and bradykinin induced weals.

SKIN HISTAMINE AND DELAYED SKIN REACTIONS. FLUOROMETRIC DETERMINATIONS ON PATCH TESTS.

Within recent years numerous investigations have been made concerning histamme m tissues. These investigations have mainly been based upon a biological method of assay originally described by Barsoum & Gaddum (2) and later modified by Code (7). The dinitrofluorobenzene(11) and dia/o-methods (16) represented as chemical methods a step forward, but their specificity has been ditficult to prove and the procedures were complicated. However in 1959, Shore, Ihirkhalter & Cohn showed that the condensation product of histamine and ortho-phthalaldehyde (OPT) gave a stable and very strong fluorescence which could be utilized for quantitative estimation of tissue histamine (23). This technique was used for a study on histamine in human skin. The present paper reports on analyses of the histamine content in positive patch tests and normal skin of patients with contact dermatitis. Besides a series of skin samples from induced primary irritant dermatitis in the same group of patients has been exammed. It also describes some of the initial experiments to evaluate the method. As stated, the method is baseci upon the fact that histamine

Histamine in a transplantable mouse mastocytoma.

Summary The histamine content of the tumor and various organs of a mouse with a transplantable mastocytoma was determined according to the spectrofluorometric method of assay. The tumor was located to the mesentery. The histamine content of the tumor was 11.797 mg per g dried and defatted tumor tissue, an extremely high value. The investigated skin from the back was also rich in histamine, while the histamine content was not found high in the other organs investigated, i.e. liver, spleen, and ovary. The author is indebted to Dr. Ragna Rask-Nielson, University Institute of Biochemistry, Copenhagen, for providing the specimens used in this study.

EFFECTS OF BP 400, AN ANTIAMINE, ON SKIN HISTAMINE AND POLYMYXIN B INDUCED WEALING

It is recognized that common antihistamine drugs have a particular affinity for receptors activated by histamine ( i , 6). This relationship between antihistamines and histamine is referred to as competitive inhibition. Lately, however, it has been proposed that, depending upon their concentration, antihistamines may act in three different ways: By competitive inhibition, by destroying mast cells and releasing histamine, and by preventing mast cell damage and histamine release (5). The present study was undertaken to investigate whether BP 400, a new antiamine drug (4, 7), might protect human mast cells against the histamine releasing effect of polymyxin B (8) . The effect of intravenous BP 400 on human skin was also studied as well as the antiwealing activity of the drug on polymyxin B induced weals.

SKIN HISTAMINE AND BASOPHILIC LEUKOCYTES IN THE NORMAL LYMPHOCYTE TRANSFER TEST

Within recent years much attention has heen paid to the search for simple methods of choosing human homograft donors. In 1963, the normal lymphocyte transfer test (N.L.T. test) was devised by Brent & Medawar ( i ) as a means of predicting the intensity of the reaction which a homograft would provoke in its recipient. These authors used guinea-pigs and expected that the test might he applicable to man. Later, Gray & Russel (3) demonstrated that intradermal injections of homologous lymphocytes in humans produced a characterictic skin reaction after 24 to 48 hours, while autologous lymphocytes produced no similar reaction. By the skin-window technic (4), JVolf-Jiirgensen & Schwartz (8) revealed a basophilia in response to homologous, but not to autologous, lymphocytes. The presence of basophils in the cellular exudate of skm-window seems to he specific for the delayedtype of hypersensitivity reactions (6), and skm-window examination has heen suggested important in the quantitative evaluation of the N.L.T. test (8) .