Troels Herlin

Heterogeneous distribution of lipoxygenase products in psoriatic skin lesions

SummarySeveral biologically active lipoxygenase products or arachidonic acid (AA) have been demonstrated in psoriatic skin lesions. The purpose of the present study was to determine the amounts of the different lipoxygenase products simultaneously in psoriatic skin. Slices of psoriatic skin were obtained at different levels with a keratome. Extracted lipids were identified by high performance liquid chromatography, UV-absorption spectrum, radioimmunoassay, and chemokinesis. Leukotriene B4 (LTB4), and 12- and 15-hydroxy-eicosatetraenoic acid (HETE) were detected in most psoriatic lesions. However, there was a remarkable variation from lesion to lesion. The biopsy specimens contained: 276.2±126.0 pg/g wet tissue of LTB4, 3,130.0±2,898.0 ng/g wet tissue of 12-HETE, and 3,633.0±1,692.0 ng/g wet tissue of 15-HETE. No correlation was found between the levels of the different lipoxygenase products. The content of each of the identified lipoxygenase products was higher in the superficial part of the biopsy specimen consisting of approximately two-thirds of the epidermis plus papillary dermis than in the lower part consisting of approximately one-third of the epidermis plus some reticular dermis. Also, there was a great variation from one anatomical region to another within the same patient. Because these lipoxygenase products possess different biological activities, the variation in their occurrence may be important for understanding their potential role in psoriasis. To determine which lipoxygenase products may be of pathogenic importance, analysis of early psoriatic lesions is warranted.

A variant form of X-linked chronic granulomatous disease with normal nitroblue tetrazolium slide test and cytochrome b

Abstract. Chronic granulomatous disease was diagnosed in a boy who suffered from severe generalized infections. Family investigations revealed the inheritance of the disease to be X‐linked. However, unlike other cases of X‐linked chronic granulomatous disease, the membrane oxidase of the neutrophils from this patient was not totally defective and sufficient activity was left to result in a normal phorbol myristate acetate‐stimulated nitroblue tetrazolium slide test. Also, unlike the usual findings in X‐linked chronic granulomatous disease, cytochrome b was present in normal amounts in the neutrophils from this patient. The cytochrome was normal, judged from its midpoint potential of —245 mV and its ability to bind CO. It is thus apparent that X‐linked chronic granulomatous disease may result from at least two different defects and that the phorbol myristate acetate stimulated nitroblue tetrazolium slide test fails to detect some cases.

Histiocytosis X--an immune deficiency disease? Studies on antibody-dependent monocyte-mediated cytotoxicity.

Six children with histiocytosis X, all in clinical remission, were investigated for antibody‐dependent cytotoxicity mediated by monocytes and neutrophils. Monocytes demonstrated a reduced cytotoxicity and a normal Fc receptor activity. ludged by light microscopy the monocytes were normal. Preincubation with the patients serum did not influence the cytotoxicity of normal monocytes. Neutrophils from patients with histiocytosis X showed a normal cytotoxic activity. We postulate a functional defect of the mononuclear phagocyte system in histiocytosis X.

Colchicine in generalized pustular psoriasis: Clinical response and antibody-dependent cytotoxicity by monocytes and neutrophils

SummaryFour patients with generalized pustular psoriasis were treated with oral colchicine in an open study. Three of the four patients went into total remission within two weeks while receiving colchicine. The monocyte- and neutrophil function was assessed by studying antibody-dependent cytotoxicity. Increased values observed before treatment decreased during treatment. The patient who responded poorest clinically also showed less changes in monocyte- and neutrophil antibody-dependent cytotoxicity.

Comparison of oxatomide and clemastine in the treatment of chronic urticaria: a double blind study

A double-blind trial comparing a new antihistaminic agent (oxatomide) with clemastine was carried out in 30 patients with chronic urticaria. The study included over-all clinical assessment by patient and clinician as well as determination of excretion of 1,4-methylimidazoleacetic acid determined by a reversed-phase ion-pair high-performance liquid chromatographic method. It was found that the effect of oxatomide was equal to that of clemastine.

Effects of cytochalasin B on glycogen metabolism in phagocytizing human polymorphonuclear leukocytes

The fungal metabolite cytochalasin B introduces an immediate, but reversible inhibition of locomotion and phagocytic activity of polymorphonu~lear leukocytes [ l-61. Bacteria and zymosan particles remain adherent to the cell surface in partial ingestion [3]. The drug also inhibits glucose transport [4]. We have reported [7] that phagocytosis of latex particles by leukocytes is dependent on the extracellular CaZ” concentration and is associated with an immediate, Ca”dependent activation of glycogen phosphorylase, resulting in glycogen breakdown. Simultaneously, but independent of extracellular Ca*+, phagocytosis elicits an increase in cyclic adenos~e-3’,5’-monophosphate (CAMP) concentration and a conversion of glycogen synthase from a metabolically active R-form [8] into the inactive D-form. As cytochalasin B blocks phagocytosis, it was therefore of interest to investigate whether the mere attachment of latex particles to the plasma membrane is sufficient to initiate the ~ycogenolytic cascade, which is normally associated to particle ingestion at all levels of extracellular glucose [9]. It is found, that in spite of greatly increased concentration of CAMP elicited by latex particles adhering to cytochalasin B-treated cells, glycogenolysis is blocked as glycogen phospho~lase remains inactive, presumably due to rapid depletion of cellular Ca*’ by cytochalasin B.

Etretinate therapy and immune reactivity

Etretinate (RO 10-9359, Tigason) is a retinoid acid derivative that has been introduced in clinical dermatology for treatment of hyperkeratotic disorders [2, 5]. It has a profound effect on the growth of epidermal cells, but can also affect other tissues such as the liver [6]. In mice, etretinate was found to increase the cytotoxic capacity of lymphocytes leading to a prolonged survival of the animals after implantation of tumor tissue. A previous report has stated that the break-down products of the retinoic acid derivative RO 10-1670 could inhibit the DNA synthesis of human lymphocytes after mitogen stimulation in vitro [1]. We therefore investigated if etretinate could change the immune reactivity in humans. Four persons took etretinate, 100rag each, every morning for 7 days and three persons in our laboratory served as controls. Blood was drawn immediately before therapy was started and on the seventh day, 1 or 2 h after the final dosage was taken. Serum was drawn just before the drug was taken and again after 3 h. We added the serum to autologous lymphocyte cultures in order to discover any possible effects of etretinate products on the lymphocyte reactivity after mitogen stimulation. A detailed description of the various techniques has been given elsewhere [3, 4]. Surface