Sustained depression of monocyte cytotoxicity in a boy with disseminated nontuberculous mycobacteriosis.
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Antibody-Dependent Cell Cytotoxicity↗
Biomedical subjects
T Herlin
Publications and source records attributed to T Herlin.
Enhanced monocyte and neutrophil cytotoxicity and normal cyclic nucleotide levels in severe psoriasis.
Eighteen patients with active psoriasis were investigated for antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by monocytes and neutrophil leukocytes. Patients with extensive psoriatic lesions showed increased ADCC whereas patients with minimal psoriasis had normal monocyte and neutrophil function. After clinical remission the ADCC became normal. No stimulatory factors in psoriatic serum could be demonstrated. The increased monocyte and neutrophil cytotoxicity in severe psoriasis is not explained by altered cyclic nucleotide levels as cAMP and cGMP levels were normal in psoriatic monocytes and neutrophils showing both increased and normal ADCC. Our results indicate that increased ADCC is secondary to the psoriatic activity.
Adolescent↗
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. Judged by light microscopy the monocytes were normal. Preincubation with the patient's 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.
Antibody-Dependent Cell Cytotoxicity↗
Dialyzable leukocyte extract stimulates cAMP in T gamma lymphocytes.
Dialyzable leukocyte extract (DLE) from human blood leukocytes gave a 3- to 8-fold increase in the cAMP concentration after addition to purified lymphocytes. No significant change in cGMP was observed. When purified lymphocytes were separated into T cells and non-T cells by an E-AET rosette technique the cAMP response was most pronounced in T cells. When further separating T lymphocytes into T cells with Fc receptors for IgG and T cells with Fc receptors for IgM (T gamma and T mu lymphocytes), the increase in cAMP following stimulation was specifically conferred to T gamma lymphocytes. Our findings may support the concept that DLE activates T gamma lymphocytes, leading to an increase in suppressor cell function.
Cell Separation↗
Antibody-dependent monocyte-mediated cytotoxicity in atopic dermatitis. Relation to clinical state and cyclic AMP response.
Antibody-dependent monocyte-mediated cytotoxicity was investigated in adult patients with atopic dermatitis. In patients with active dermatitis monocyte cytotoxicity was reduced. Serial studies of individual patients demonstrated that a reduced cytotoxicity in clinical exacerbation did not normalize during clinical remission. The reduced monocyte cytotoxicity was not caused by an abnormal influence of lymphocytes. During the cytotoxicity reaction a rapid and transient elevation of monocyte cyclic AMP occurred. In atopic dermatitis this elevation was decreased, but no relation was found between the monocyte cytotoxicity and the cyclic AMP response in these patients.
Adult↗
Oral disodium cromoglycate in mastocytosis.
Oral disodium cromoglycate was found useful for the treatment of gastrointestinal manifestations of mastocytosis in 2 patients with systemic disease. The urinary excretion of histamine in these 2 patients decreased following treatment. Oral disodium cromoglycate had no effect on cutaneous symptoms, either in these 2 patients nor in 2 other patients with urticaria pigmentosa without signs of systemic mastocytosis. In the latter 2 patients the urinary excretion of histamine was unaffected. Treatment was given for 4 to 6 weeks and the dose of disodium cromoglycate was 100 mg four times daily in the 3 adult patients and 100 mg three times daily in the fourth patient, an 8-year-old boy.
Administration, Oral↗
Transient cyclic AMP accumulation during antibody-dependent cytotoxicity mediated by monocytes and neutrophils.
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Antibody-Dependent Cell Cytotoxicity↗
Impaired monocyte-mediated cytotoxicity in atopic dermatitis.
Twenty-three adult patients with atopic dermatitis of different severity and extent all without present cutaneous infection were investigated for antibody-dependent cytotoxicity mediated by purified monocytes. Compared to a healthy control group the monocyte cytotoxicity was significantly decreased for patients with more widespread dermatitis. Eight patients with acute contact dermatitis and 13 patients with extrinsic asthma or allergic rhinitis showed normal cytotoxicity. Decreased monocyte cytotoxicity in atopic dermatitis was not related to the serum IgE level. In vitro cultivation of defective monocytes from atopics did not increase cytotoxicity, nor did normal monocytes preincubated with patient serum show abnormal function. In atopic dermatitis the total number of Fc receptor bearing monocytes was normal. However, the affinity of this receptor was lower than in normals. Serial studies are needed to establish whether reduced monocyte function is a basic pathophysiologic defect in atopic dematitis.
Adolescent↗
Impaired monocyte cyclic AMP responses and monocyte cytotoxicity in atopic dermatitis.
Purified monocytes from 21 patients with mild and severe atopic dermatitis (AD) were compared with 22 healthy controls with respect to antibody-dependent cell-mediated cytotoxicity (ADCC) and cyclic adenosine 3',5'-monophosphate (cAMP) responses to stimulatory agents. ADCC was depressed in both severe and mild atopic dermatitis. The patients showed decreased cAMP responses to isoproterenol and histamine, the decrement being more distinct in severe atopic dermatitis. Formation of cAMP was diminished with PGE1 only in patients with severe AD. ADCC is inhibited by the agents that increase cAMP. In the severe dermatitis group reduced inhibition induced by isoproterenol, histamine, but not PGE1, was obtained. It is suggested that a general suppression of membrane activation may explain the reduced cAMP responses to various stimulatory agents and the impaired monocyte cytotoxicity.
Adolescent↗
Antibody-dependent monocyte-mediated cytotoxicity. The interference by platelets, immune complexes, and normal serum.
Monocyte mediated lysis of human type B-erythrocytes coated with heat-inactivated anti-B serum was measured as 51Cr-release. Preincubation of monocytes with heat-inactivated normal AB serum inhibited cytolysis while a strong stimulation of cytolysis was seen with fresh AB serum. These effects of serum were reversible upon cell washing. Preincubation of monocytes with hyperimmune human serum against type B erythrocytes did not alter the cytolysis. After incubation at 37 degrees C of monocytes with immune complexes formed of human albumin and rabbit anti-human albumin a dose-related inhibition of cytolysis was observed. This inhibition was equally expressed at different albumin to anti-albumin ratios. Pretreatment with immune complexes at 4 degrees C had the same effect on cytolysis as pretreatment at 37 degrees C. The effect of immune complexes on monocyte-mediated cytolysis was resistant to repeated cell washing. After incubation of pretreated monocytes at 37 degrees C for up to 18 h some of the inhibition disappeared, but without normalization. Platelet depletion of monocyte suspensions resulted in a significant increase of cytolysis, and addition of washed platelets reinduced a decreased of cytolysis, which correlated with the number of platelets added.
Animals↗
Effects of cytochalasin B on glycogen metabolism in phagocytizing human polymorphonuclear leukocytes.
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Calcium↗
The role of calcium and cyclic adenosine 3',5'-monophosphate in the regulation of glycogen metabolism in phagocytozing human polymorphonuclear leukocytes.
Incubation of human polymorphonuclear leukocytes in a glucose-free Krebs-Ringer bicarbonate buffer for 2 h resulted in glycogen depletion, decreased phosphorylase activity and increased synthase-R activity. Addition of dialyzed latex particles to starved leukocytes revealed a very rapid ingestion rate (half-maximal ingestion within 30 s). This uptake is followed by glycogenolysis associated with an immediate two-fold increase in phosphorylase a activity and a synthase-R to -D conversion within 30 s. Furthermore, in rapid time-course experiments with phagocytozing cells we found that the concentration of cyclic AMP increased by 93% within 15 s and returned to baseline values at 1 min. In a medium without added calcium and with 1 mM ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid, phagocytosis was blocked, cyclic AMP formation decreased by 50% and phosphorylase activation was abolished, but the conversion of synthase-R to -D was preserved. Addition of calcium ions to cells suspended in a calcium-free buffer without added latex results in phosphorylase activation and glycogenolysis, but not in cyclic AMP increase or synthase-R to -D conversion. Measurements of 45Ca efflux during phagocytosis suggest an initial increase in cytosolic calcium obtained by a release of membrane-bound 45Ca. Activation of phosphorylase during phagocytosis is thus presumably due to an increase in cytosol Ca2+ and subsequent activation of phosphorylase kinase, and is independent of the simultaneous increase in concentration of cyclic AMP. Phosphorylation of synthase R to the D form does not depend on the presence of Ca2+ in the extracellular phase.
Calcium↗
Effects of catecholamines and glucagon on glycogen metabolism in human polymorphonuclear leukocytes.
Addition of 10 micron of the alpha-adrenergic agonist phenylephrine to polymorphonuclear leukocytes suspended in glucose-free Krebs-Ringer bicarbonate buffer (pH 6.7) activated phosphorylase, inactivated glycogen synthase R maximally within 30 s, and resulted in glycogen breakdown. Phenylephrine increased 45Ca efflux relative to control of 45Ca prelabelled cells, but did not affect cyclic adenosine 3',5'-monophosphate (cAMP) concentration. The effects of phenylephrine were blocked by 20 micron phentolamine and were absent in cells incubated at pH 7.4. The same unexplained dependency of extracellular pH was observed with 2.5 nM--2.5 micron glucagon, which activated phosphorylase and inactivated synthase-R, but in addition caused a 30-s burst in cAMP formation. 25 nM glucagon also increased 45Ca efflux. The activation of phosphorylase by phenylephrine and possibly also by glucagon are thought mediated by an increased concentration of cytosolic Ca2+ activating phosphorylase kinase. The effects of 5 micron isoproterenol or 5 micron epinephrine were independent of extracellular pH 6.7 and 7.4 and resulted in a sustained increase in cAMP, an activation of phosphorylase and inactivation of synthase-R within 15 s, and in glycogenolysis. The effects of both compounds were blocked by 10 micron propranolol, whereas 10 micron phentolamine had no effect on the epinephrine action. The efflux of 45Ca was not affected by either isoproterenol or epinephrine. The beta-adrenergic activation of phosphorylase is consistent with the assumption of a covalent modification of phosphorylase kinase by the cAMP dependent protein kinase. Phosphorylation of synthase-R to synthase-D can thus occur independently of increase in cAMP, but the evidence is inconclusive with respect to the cAMP dependent protein kinase also being active in this phosphorylation.
Calcium↗
Knemometry in children with atopic dermatitis treated with topical glucocorticoids.
Recently the knemometer, a lower leg length measuring device, has been introduced for sensitive assessment of systemic activity of exogeneous glucocorticoids in children. The aim of this study was to assess by means of knemometry whether the topical glucocorticoid budesonide affects short-term growth in children with atopic dermatitis. Fourteen children 5 to 12 years old were studied in an open longitudinal trial with three periods of 2 weeks duration. In periods 1 (run-in) and 3 (run-out), the children were treated with emollient. In period 2, budesonide cream 0.025% was followed by emollient twice daily to all of the body except the face. Eczema was evaluated according to a score based on extent and activity. Knemometry was performed twice weekly. Compared to the run-in and run-out periods the mean growth rate during budesonide treatment was reduced by 0.11 mm/wk (p > .05) and 0.40 mm/wk (p < .05), respectively. The mean growth rate during run-out was increased by 0.29 mm/wk as compared to run-in (p < .05). Compared to run-in the mean severity indices during budesonide treatment and run-out were reduced by 1.55 (p < .05) and 1.55 points (p <.05), respectively. The concomitant variations in lower leg growth rate and disease activity suggest that short-term treatment with topical glucocorticoids may provide a better growth potential during the weeks after withdrawal of the treatment. Whether this is due to improved disease control needs further study. Being a noninvasive method, knemometry may be useful for comparing different topical glucocorticoids and administration regimens in children in whom vasoconstrictor assays are difficult.
Administration, Topical↗
The effect of TNFalpha blockade in complicated, refractory Kawasaki disease.
In Kawasaki disease (KD), a systemic vasculitis of childhood, serum levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFalpha) are elevated during the acute phase of the disease. Although the majority of children recover completely from a single dose of intravenous immunoglobulin (IVIG), the treatment is not always effective. In refractory cases of KD there are no documented treatment guidelines. A future role of biological agents directed against proinflammatory cytokines has recently been suggested by the American Heart Association (AHA). We describe two infants with severe KD, complicated by coronary as well as extracoronary aneurysms, who responded neither to repeated treatment with IVIG plus aspirin nor to corticosteroids. The children were subsequently treated with infliximab. In both cases, the effect was prompt and long-lasting. Clinical improvement was seen within a few days after the first dose, and regression of the aneurysms occurred within weeks.
Anti-Inflammatory Agents↗
The Danish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).
We report herein the results of the cross-cultural adaptation and validation into the Danish language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Danish CHAQ-CHQ were fully validated with 3 forward and 3 backward translations. A total of 139 subjects were enrolled: 76 patients with JIA (25% systemic onset, 30% polyarticular onset, 19% extended oligoarticular subtype, and 26% persistent oligoarticular subtype) and 63 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Danish version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.
Adolescent↗
Contrast-enhanced MRI compared to histological findings in the temporomandibular joint of antigen-induced arthritis in young rabbits.
OBJECTIVE: To study the correlation between histological findings and Magnetic Resonance Imaging (MRI) findings in experimentally induced arthritis in the temporomandibular joint (TMJ) of growing rabbits and to study the effect of intraarticular corticosteroid injections. METHODS: Arthritis was induced by ovalbumin in the left TMJ of 44 pre-sensibilized rabbits. Nine animals died during this procedure. Eight of the remaining animals with induced arthritis were treated with intraarticular corticosteroid injections one week after induction of arthritis. Twelve rabbits served as controls. MRI enhanced with Gadolinium-DTPA was performed on all animals 1 to 2 weeks after induction of arthritis and again before sacrifice and the degree of enhancement was calculated. Histology of the condyle was performed and degree of villous hyperplasia, synovial thickness, infiltration of inflammatory cells and pannus was graded. RESULTS: TMJ arthritis was successfully induced in the rabbits and was verified by enhancement of the MRI and by histological changes one week after the induction. Joints treated with intraarticular corticosteroid injections revealed complete inhibition of the inflammation. CONCLUSION: Enhancement of MRI in antigen-induced arthritis in the TMJ associated well with inflammatory changes shown histologically. An intraarticular corticosteroid injection prevents the initial inflammatory response in experimentally induced TMJ arthritis.
Adjuvants, Immunologic↗