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.     

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 mono cyte 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.     

Learning Disabilities in Children: Significance of Low-Level Lead-Exposure and Confounding Factors

Abstract. The hypothesis that low-level lead absorption is a risk factor for learning disabilities in school children was examined in the municipality of Aarhus, Denmark. During 1982-1983, a total of 1302 children in the first grade (54 % of the eligible population) delivered shed deciduous teeth. The lead concentration in the circumpulpal dentin was used as an indicator of the cumulated lead absorption, and 200 cases (high-lead) and controls (low-lead) were selected, and matched for socioeconomic group and gender. The parents were interviewed regarding the child's development and past medical history. Possible confounders were identified and controlled for in a logistic multivariate model. The influence of lead absorption became statistically signincant only after exclusion of the children with proven medical risk factors, thereby the adjusted odds ratio in the weighted analysis was changed from 2.2 to 4.3. Thus, in a Scandinavian low-level lead-polluted area, lead absorption appears to be a risk factor for learning disabilities.     

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 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.     

The geometry of the thiopeptide unit

The structure of the modified dipeptide Z-Glyt-Gly-OBzl is reported with special emphasis on the linear and angular dimensions of the thiopeptide unit. It is shown that, except for the differences between the carbonyl and the thioacyl bond lengths, there are no significant differences between the oxopeptide and the thiopeptide unit.     

Effects of Cisapride on Gastroparesis in Patients with Insulin-dependent Diabetes Mellitus

ABSTRACT Fourteen insulin-dependent diabetics with symptoms and signs of delayed gastric emptying were treated with a new prokinetic agent, cisapride. In a placebo-controlled cross-over trial no significant differences from placebo was found regarding overall symptomatic effects and effects on gastric emptying of a mixed solid/liquid isotope marked test meal. Solid emptying was most markedly delayed in diabetics compared with healthy controls, but the emptying rate was not correlated to the severity of symptoms as observed for liquid emptying. During active tratment with cisapride the amelioration of symptoms was correlated to increased emptying rates assessed by combined measure of liquidsolid gastric emptying.     

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.     

Red blood cell membrane-bound IgG: demonstration of antibodies in patients with autoimmune haemolytic anaemia and immune complexes in patients with rheumatic diseases

Summary. Immunoglobulin G (IgG) bound in vivo to the surfaces of red blood cells (RBC-IgG) was quantificated by an enzyme-linked immunosorbent assay (ELISA) using the cells themselves as solid phase. The method was applied on RBC from normal subjects, patients with autoimmune haemolytic anaemia (AIHA) and rheumatoid patients with and without circulating immune complexes (CIC). Small amounts of RBC-IgG were detected in normal subjects and rheumatoid patients without CIC. Fifteen out of 16 patients with AIHA had increased RBC-IgG indicating RBC sensitization with IgG antibodies, although only eight patients had a positive direct antiglobulin test (DAT) with anti-IgG. Ten out of 13 rheumatoid patients with a negative DAT and with CIC had increased RBC-IgG suggesting RBC C3 receptor-bound IC. The results provide background for further studies of the significance of RBC-IgG in health and disease.