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Biomedical subjects

K Kragballe

Publications and source records attributed to K Kragballe.

At least 163 records · Page 9Linked to original sources
PubMed1985

Normalization of monocyte chemotaxis precedes clinical resolution of psoriasis treated with benoxaprofen.

Enhanced monocyte activity is present in psoriasis, and benoxaprofen is a drug that inhibits several aspects of monocyte function. To assess a potential pathogenic role of enhanced monocyte function in psoriasis, we determined monocyte chemotaxis and monocyte antibody-dependent cell-mediated cytotoxicity (ADCC) at week 0, 2, 4 and 8 in psoriatics being treated with benoxaprofen. In patients responding to benoxaprofen, normalization of monocyte chemotaxis occurred at week 4, before clinical resolution took place. A significant decrease of monocyte ADCC was also present at week 4, but it was only at week 8, when psoriasis had completely cleared, that monocyte ADCC was completely normalized. In patients receiving placebo or receiving benoxaprofen, but showing no or minimal clinical improvement, monocyte functions remained increased. These results are compatible with the idea that benoxaprofen may improve psoriasis by interfering with monocyte function.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

Calcium efflux changes in neutrophils from patients with severe atopic dermatitis.

In seven patients with severe atopic dermatitis (AD) we investigated the 45Ca-efflux responses from prelabelled neutrophils stimulated with the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (F-Met-Leu-Phe) and catecholamines. We found no difference between the burst in 45Ca-efflux induced by F-Met-leu-Phe in AD patients when comparing with controls. Alpha 1-receptor responses are believed to be mediated by a calcium mechanism and like normal cells the 45Ca-efflux rate in AD neutrophils was unchanged both after stimulation with alpha- and beta-receptor agonists. Whereas the cAMP-hyporesponsiveness of beta-adrenergic receptors is known in atopic disease our present study might indicate a normal alpha-adrenergic response in AD neutrophils.

Adolescent↗
PubMed1985

Arachidonic acid in psoriasis. Pathogenic role and pharmacological regulation.

AA and its derivatives are a family of potent mediators and regulators of inflammation. There are several pieces of evidence to suggest a pathophysiologic role of certain AA derivatives in psoriasis. The complexity of the pathways in the generation of LTs and other LO products suggests that carefully designed systems will be needed to establish the exact role of these compounds in the pathogenesis of diseases such as psoriasis, and to test the effects of pharmacological inhibitors.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1984

Abnormal monocyte cytotoxicity and cyclic-AMP levels in systemic sclerosis.

Monocyte antibody-dependent cell-mediated cytotoxicity (ADCC) was compared to intrinsic cyclic-adenosine-monophosphate (cAMP) levels in 14 patients with systemic sclerosis. Depressed monocyte cytotoxicity was observed. Elevated cAMP levels (2-5 times) in resting monocytes were found in 5 patients; the rest had normal cAMP values. Monocyte ADCC was inversely correlated to cellular cAMP content (r = -0.6659, P less than 0.02). Scleroderma patients with high basal cAMP levels showed impaired responses to beta-adrenergic stimulation but not to prostaglandin E (PGE1) and histamine. Patients with normal basal cAMP levels showed no defect in beta-adrenergic responses. No close correlation between monocyte abnormality and clinical state was found.

Adult↗
PubMed1984

Modulation of epidermal cell division and growth by oxygenation products of arachidonic acid.

Recently accumulated data have shown that arachidonic acid derivatives play a role not only in cutaneous inflammation, but also in regulation of epidermal growth. Today, the best evidence for the involvement of leukotrienes in human skin disease is psoriasis. Such evidence includes: the presence of leukotrienes B4, C4, and D4 and monohydroxy-eicosatetraenoic acids in psoriatic skin lesions; the presence of these compounds in amounts capable of mediating epidermal proliferation, neutrophil accumulation, and vasodilatation characteristic of psoriasis; and improvement of psoriasis by 5-lipoxygenase inhibitors.

Animals↗
PubMed1984

Histologic changes in the liver during etretinate treatment.

Histologic changes in the liver were evaluated in thirty-two patients with different dyskeratotic dermatoses treated with etretinate (Tigason) during an average of 24.9 months. Fatty infiltration, nuclear variability, periportal inflammation, focal necrosis, fibrosis, and cholestasis were estimated. The usual dose was 50-75 mg/day, with reduction according to efficacy and side effects. No statistically significant differences were found between a control group of thirty-five liver biopsies from psoriasis patients who had not received systemic therapy and biopsies from the patients treated with etretinate. Among the thirty-two etretinate-treated patients, six had two serial biopsies, and eight had pretreatment biopsies. No significant changes appeared during therapy.

Adolescent↗
PubMed1984

Studies of peripheral blood monocytes in pulmonary sarcoidosis.

In 14 patients with pulmonary sarcoidosis and 14 matched controls we studied peripheral blood lymphocyte and monocyte counts, distribution of T and B lymphocytes, the functional helper:suppressor T cell balance, the antibody-dependent cell-mediated cytotoxicity of monocytes (monocyte ADCC), and the capacity of peripheral monocytes to generate angiotensin converting enzyme (ACE) in culture. Apart from lymphopenia in sarcoidosis patients we found a normal lymphocyte subset distribution and no evidence of increased suppressor T cell activity, using a PWM driven proliferative assay. The patients exhibited a normal monocyte count, but the proportion of monocytes was increased in sarcoidosis. Patients with active sarcoidosis had a significantly increased monocyte ADCC which was positively correlated with raised serum ACE. Peripheral monocytes had a measurable, but low ACE activity, which was modestly higher in active sarcoidosis than in controls. We could not reproduce earlier reported results on a glucocorticoid induced ACE synthesis from cultured human monocytes.

Adult↗
PubMed1983

Facilitation of cAMP increments during ADCC mediated by monocytes pretreated with cAMP-elevating agents.

Addition of IgG-sensitized human erythrocytes to peripheral blood monocytes elicit a transient increment in monocyte cAMP levels. This increase in cAMP was facilitated when monocytes were preincubated with the phosphodiesterase inhibitors, isobutylmethylxanthine (IBMX) and theophylline, and the adenylate cyclase agonists, isoproterenol and prostaglandin E1 (PGE1). Although these cAMP elevating agents were able to inhibit monocyte ADCC, the degree of inhibition could not be anticipated from the cAMP levels achieved by these drugs since theophylline inhibited monocyte ADCC in doses not elevating cAMP and PGE1, isoproterenol and IBMX were less effective inhibitors of monocyte ADCC than theophylline when comparing their effects on cAMP levels. Both PGE1-induced elevation of cAMP levels and the further increments of cAMP after addition of IgG-sensitized erythrocytes to PGE1-treated monocytes were significantly correlated to the inhibition of beta-glucuronidase release during ADCC. Theophylline in doses of 0.5 mM did not elevate basal levels of monocyte cAMP but facilitated the ADCC-induced cAMP increment concomitant with inhibition of monocyte ADCC and degranulation. Possibly, facilitation of cAMP increments during ADCC by an inhibitory feedback mechanism may be responsible for the inhibition caused by cAMP-elevating agents.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Methotrexate in psoriatic arthritis: a retrospective study.

The response of psoriatic arthritis to methotrexate was evaluated retrospectively in 59 consecutive patients. Initially almost all received 15 mg weekly. When clinical improvement occurred, the dose was gradually reduced. In 7 patients methotrexate had to be discontinued within a year due to adverse reactions. The remaining 52 patients were treated from 1 to 11 years, median 3 years. Among these a modest improvement was seen in 21, while in 22 the signs of inflammatory joint disease almost disappeared. The favourable response was related to the short duration of arthritis, but unrelated to the severity of the disease.

Adolescent↗
PubMed1983

Benoxaprofen improves psoriasis. A double-blind study.

The pathophysiologic significance of increased levels of lipoxygenase compounds in psoriatic lesions was assessed in a double-blind randomized clinical study with the 5-lipoxygenase inhibitor, benoxaprofen. Forty patients with psoriasis vulgaris were treated with 600 mg of oral benoxaprofen daily or a placebo for a period of eight weeks. Benoxaprofen therapy provided excellent treatment results in about 75% of the cases. In the placebo group, only minimal improvement occurred. Most patients receiving benoxaprofen therapy reported side effects including photosensitivity, onycholysis, milia, diarrhea, and edema. In two cases, benoxaprofen was withdrawn before completion of the treatment course because of photosensitivity. Benoxaprofen may affect psoriatic epidermis either directly by the inhibition of epidermal 5-lipoxygenase or indirectly by the inhibition of the accumulation of phagocytes in psoriatic lesions. Despite serious side effects from benoxaprofen therapy, lipoxygenase-inhibiting agents deserve further study in the treatment of psoriasis.

Adult↗
PubMed1983

Stimulation of monocyte-mediated, antibody-dependent cytotoxicity in mycosis fungoides.

Antibody-dependent cytotoxicity mediated by purified blood monocytes were determined in untreated patients with plaque-stage mycosis fungoides (MF), parapsoriasis en plaques, exfoliating erythroderma, and noncutaneous malignant lymphoma. Compared with healthy control subjects and control subjects with varicose ulcers, patients with MF had increased monocyte cytotoxicity. In the other dermatoses, normal monocyte cytotoxicity was found. Patients with noncutaneous malignant lymphoma showed normal or decreased monocyte cytotoxicity. There was no evidence that abnormal monocyte cytotoxicity in cutaneous and noncutaneous malignant lymphoma were caused by interaction with lymphocytes or serum. The presence of increased monocyte cytotoxicity in patients with plaque-stage MF may be a clinically useful finding when this diagnosis is suspected clinically but not proved histopathologically.

Adult↗
PubMed1982

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

Four 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.

Administration, Oral↗
PubMed1982

On the mechanism of enhanced monocyte and neutrophil cytotoxicity in severe psoriasis.

Monocyte and neutrophil function assessed as antibody-dependent cell-mediated cytotoxicity (ADCC) using IgG-sensitizing human erythrocytes as target cells was enhanced in patients with severe psoriasis when compared to healthy controls. We found significant correlation between increased monocyte ADCC and increased neutrophil ADCC, No differences in basal cAMP levels and cAMP responses during initiation of the ADCC reaction was observed between psoriatics and normals. Also degranulation determined as lysozyme release during ADCC was normal. In contrast, the increase in ADCC was significantly correlated to an enhanced hexose monophosphate shunt activation in the effector cells during the cytotoxic reaction. Activity of enzymes responsible for the respiratory burst was not altered in psoriasis since superoxide production after stimulation with phorbol myristate acetate was normal. Likewise, oxygen consumption and degranulation following phagocytosis of opsonized zymosan particles in neutrophils was found normal in psoriasis. Since monocytes showed increased binding of IgG-sensitized erythrocytes these data indicate that the enhanced monocyte and neutrophil ADCC is caused by an enhancement of the respiratory burst possibly induced by increased Fc receptor activity.

Adult↗