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Biomedical subjects

T Herlin

Publications and source records attributed to T Herlin.

At least 73 records · Page 4Linked 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

Neutrophil and monocyte chemotaxis in methotrexate-treated psoriasis patients.

Polymorphonuclear leukocyte (PMN) and monocyte (MO) chemotaxis in methotrexate (MTX)-treated psoriatics was determined by a radioactive in vitro assay. MTX was administered orally once a week in a dose of 7.5 mg to 15 mg. Six untreated patients were examined before start and during the first week of the MTX treatment. A profound depression of the enhanced levels of PMN and MO chemotaxis was seen within the first 48 hours after intake of MTX, but the chemotactic activity recovered to initial values during the following days. Fifteen psoriasis patients in long-term treatment with MTX had normal chemotactic responses of both PMN's and MO's.

Adult↗
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

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

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

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.

Adolescent↗
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

Early changes in cyclic AMP and calcium efflux during phagocytosis by neutrophils from normals and patients with chronic granulomatous disease.

During phagocytosis of serum-treated zymosan particles (STZ) human neutrophils respond within 5 sec by a two-fold increase in cAMP concomitantly with an increase in 45Ca-efflux from intracellular stores. The changes in cyclic AMP and calcium efflux during phagocytosis were essentially the same whether the cells were preincubated in the presence of 5 mM glucose or without glucose. However, the phagocytic capacity, and oxygen consumption and degranulation during phagocytosis were reduced about 20%-25% in the absence of glucose. Addition of 2-deoxyglucose and iodoacetamide, which results in depletion of cellular ATP, abolished the cAMP increments during phagocytosis and profoundly inhibited calcium efflux. At the same time, the phagocytic capacity and STZ-induced oxygen consumption and degranulation were severely impaired. The mitochondrial inhibitors, cyanide, azide, and antimycin A, in the presence of glucose, did not affect the cellular ATP levels. Neither were cAMP increments and calcium effluxes during phagocytosis affected by these drugs, and likewise these did not affect phagocytosis or the post-phagocytic events. Neutrophils from two patients with X-linked chronic granulomatous disease (CGD) and one patient with the autosomal recessive form elicited normal increases in cAMP levels and calcium effluxes after addition of STZ despite no increase in oxygen consumption showing that these early metabolic events are not affected by the lack of oxidase function.

Adenosine Triphosphate↗
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↗
PubMed1982

Divergent effects of methylxanthines and adenylate cyclase agonists on monocyte cytotoxicity and cyclic AMP levels.

The effects of theophylline, isobutylmethylxanthine (IBMX), prostaglandin E1 (PGE1), and isoproterenol on monocyte antibody-dependent cytotoxicity (ADCC) were compared with their effects on monocyte cyclic adenosine 3':5'-monophosphate (cAMP) levels. Theophylline (2 mmol/l) halved ADCC and gave a 2-fold increase in cAMP levels. At concentrations not elevating cAMP theophylline inhibited ADCC significantly. In comparison, incubation of monocytes with IBMX, PGE1 and isoproterenol ADCC was only modestly inhibited while these agents gave larger increments (3- to 8-fold) in cAMP levels than theophylline did. Low concentrations of IBMX (50 mumol/l) elevated cAMP without affecting monocyte ADCC whereas PGE1 and isoproterenol inhibited ADCC dose-dependently comparable to increases in cAMP. However, in doses giving similar inhibition of ADCC addition of PGE1 resulted in larger cAMP increments than isoproterenol. The effects of IBMX, PGE1 and isoproterenol was dependent on target cell to effector cell ratio and increased during preincubation with the agents. The inhibition of ADCC by the agents was accompanied by a depressed monocyte lysozyme release and depressed activation of hexose monophosphate shunt. However, only theophylline affected monocyte attachment to sensitized target cells. These results argue against the general inverse relationship between cAMP content and inhibition of monocyte ADCC and demonstrate that theophylline independent on increases in cAMP inhibits ADCC probably by abrogation of monocyte binding activity.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Energy metabolism of human neutrophils during phagocytosis.

Detailed quantitative studies were performed on the generation and utilization of energy by resting and phagocytosing human neutrophils. The ATP content was 1.9 fmol/cell, was constant during rest, and was not influenced by the presence or absence of glucose in the medium. The intracellular content of phosphocreatine was less than 0.2 fmol/cell. In the presence of glucose, ATP was generated almost exclusively from lactate produced from glucose taken up from the surrounding medium. The amount of lactate produced could account for 85% of the glucose taken up by the cells, and the intracellular glycosyl store, glycogen, was not drawn upon. The rate of ATP generation as calculated from the rate of lactate production was 1.3 fmol/cell/min. During phagocytosis, there was no measurable increase in glucose consumption or lactate production, and the ATP content fell rapidly to 0.8 fmol/cell. This disappearance of ATP was apparently irreversible since no corresponding increase in ADP or AMP was observed. It therefore appears that this phagocytosis-induced fall in ATP concentration represents all the extra energy utilized in human neutrophils in the presence of glucose. In the absence of glucose, the rate of ATP generation in the resting cell was considerably smaller, 0.75 fmol/cell per min, as calculated from the rate of glycolysis, which is sustained exclusively by glycogenolysis. Under this condition, however, phagocytosis induces significant enhancement of glycogenolysis and the rate of lactate production is increased by 60%, raising the rate of ATP generation to 1.2 fmol/cell per min. Nonetheless, the ATP content drops significantly from 1.9 to 1.0 fmol/cell. Neutrophils from patients with chronic granulomatous disease have the same rate of glycolysis and the same ATP content as normal cells, thus confirming that the defective respiration of these cells does not affect their energy metabolism.

Adenine Nucleotides↗