Basophil Histamine Release in Cord Blood Regulatory Role of IgE

Thirty-two cord blood samples were studied for histamine releasing capability by using a sensitive glass microfibre-based histamine analysis. Histamine was obtained after challenge with anti-IgE in 24 of the 32 samples. However, the net release in cord blood was only 25% of that in adult blood and no relationship was found between histamine release response, total IgE in cord plasma, and a family history of atopic diseases. The low histamine release in cord blood seemed to be associated with the immunological IgE receptor complex activation and not with an immature basic cell function, since the calcium ionophore A23187 which bypasses the receptor complex induced identical histamine release curves in cord and adult blood. Furthermore, when comparing the results of passive sensitization of basophils from new-born and adult persons, the new-born basophils possessed a significant fraction of free IgE receptors, whereas in adults most of the receptors were occupied by IgE.     

Membrane sialic acid influences basophil histamine release by interfering with calcium dependence

The influence of the cell membrane content of sialic acid on basophil histamine release was examined in vitro in allergic patients and normal controls. Enzymatical removal of sialic acid enhanced histamine release induced by allergen and anti-IgE, whereas an increase in membrane sialic acid content by insertion of sialic acid containing gangliosides into the membrane inhibited the mediator release. The reduction in membrane sialic acid content abolished the inhibitory capacity of the calcium channel antagonist nimodipine, whereas the inhibition produced by verapamil and lanthanum was not affected. This difference, together with the previous finding that alterations in membrane sialic acid content is reflected in the cell sensitivity to extracellular calcium, suggest an interaction between membrane sialic acid and the calcium channels involved in basophil histamine release.     

Different Patterns of Mast Cell Activation by Muscle Relaxants in Human Skin

Background: Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects.

Methods: Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves.

Results: For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase.     

Impaired basophil histamine release from allergic patients

A few patients (6-7%) with a verified type I allergic reaction do not respond with histamine release after challenge of their basophils with specific antigen (non-responding basophils from allergic patients). Sera from these non-responding patients were used for passive sensitization of responding cells from healthy controls. When these sensitized cells were challenged with specific antigen, histamine release was observed indicating that the non-responding allergic patients have circulating antigen-specific IgE capable of binding to Fc-receptors on the basophils. These findings suggest the possibility that non-responding basophils have impaired cell functions. We therefore examined the influence of enhanced IgE receptor stimulation on histamine release in non-responding basophils. This was made by stimulating protein kinase C activity by a phorbol ester (phorbol 12-myristate 13-acetate). When the non-responding cells were incubated with the phorbol ester and challenged with either anti-IgE or specific antigen, the cells released histamine. These findings support the hypothesis that the unresponsiveness of basophils in some allergic patients is associated with impaired IgE receptor complex activation or subcellular functioning and not with a lack of cell-bound IgE.     

Bacteria and their products peptidoglycan and teichoic acid potentiate antigen-induced histamine release in allergic patients

Histamine release was examined in leukocyte suspensions from patients allergic to grass pollen, mite or cat dander or to bacteria (antigen). When the cells were challenged with specific antigen plus bacteria to which the person was not sensitized, these bacteria were found to potentiate the allergic histamine release. The potentiating effect by bacteria might be due to the bacterial cell wall components, peptidoglycan and teichoic acid, which mimic the effect of bacteria.     

CT scanning for definitive radiotherapy planning of prostate cancer: necessity or nicety? Results from survey of radiation oncologists working at different institutions in Australasia

Interactive computerised tomographic (CT) planning techniques offer the prospect of better anatomical localisation, more consistent tumour coverage, and limiting normal tissue dose. However, its value in the management of prostate cancer remains undefined. The present study addresses the impact of planning CT on the designated target volumes for localised carcinoma of the prostate at a multi-institution national level. Nine radiation oncologists from different centres in Australia and New Zealand were asked to designate a target volume on five sample patients with different disease stages (A2-C2) using both conventional cystogram films and planning CT scans. Target volumes estimated by CT means in this study differed by more than 10% from those estimated by conventional means in 75.6% of instances, being smaller in 55.6%. Volumes varied widely between individual radiation oncologists, both using conventional planning and CT information. These variations were found to exceed any differences in the volume caused by the planning technique itself. Results from this survey suggest that volumes appear to change more according to the individual radiation oncologist rather than to any other factor. In most or all of the sample cases six of nine radiation oncologists defined the borders of their CT volumes to be either consistently smaller (5 out of 9) or greater (1 out of 9) than their conventionally defined borders. The results of this survey are potentially important and warrant repetition with larger sample numbers in other countries where interactive CT planning facilities exist, both with and without diagnostic radiological input, to exclude similar variation and to define causes for any variations that do become apparent.     

Stimulation of histamine synthesis from tumour cells by concanavalin A and A23187

In the present study the amount of histamine synthesized by two experimental tumour cell lines, the Yoshida ascites sarcoma cells and SEWA cells, was measured after stimulationin vitro with the calcium ionophore A23187 and the plant lectin Concanavalin A (Con A). After 7 hrs of incubation with the two stimulators, histamine could be measured and the amount was still increasing up to 15 hrs of incubation with a maximal net histamine production of approximately 1.0 ng histamine per 10⁶ tumour cells per ml sample.In addition, the tumour promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) was found to enhance the synthesis of histamine in the presence of Con A or A23187, except in high concentrations, i.e. 50 ng/ml TPA, where an inhibitory effect was seen. TPA alone could not induced detectable histamine synthesis.In order to measure the histamine, the tumour cells were incubated in glass microfibre-based microtiter plates, which have been shown to bind histamine with high affinity and selectivity.The aim has been to develop a functionalin vitro tumour assay which can detect histamine from tumour cells and which can be used to measure pharmacological interaction of the tumour cell function as well as histamine production from different tumour cell types.     

Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study

Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally. Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol, and were excluded. The remaining 40 patients received the test preparations for 3 to 12 weeks, with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine. Clinical evaluations were done at baseline and at weeks 1, 2, 4, 6, 8, and 12 including the CGI, a CPRS subscale for schizophrenia, and the UKU Side Effects Rating Scale. The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily. Statistically, significant reductions on the CGI, severity of illness, and on the CPRS (total score) were found for both drugs when comparing baseline with later scores. No significant differences between the drugs were found. It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS. Although small differences between the two drugs were found, as regards number and type of side effects, it is concluded that the pattern of side effects was almost identical in the two treatment groups.