The cardiac and renal effects of the complement fragment C5a des Arg are partly mediated by the release of histamine and arachidonic acid metabolites

This report suggests that the release of various inflammatory mediators such as histamine, LTC₄, D₄ and E₄, and TXA₂ measured as the stable metabolite TXB₂ are partly responsible for the various cardiac and renal effects of the complement fragment C5a des Arg anaphylatoxin, in addition to its direct vasoconstrictor activity.     

Cardiac and renal mast cells: morphology, distribution, fixation and staining properties in the guinea pig and preliminary comparison with human

In guinea pig (GP) and human heart and kidney cell or tissue preparations fixed with Carnoy's fluid (but not with formol-saline), mast cells (MC) were extremely well preserved and could be detected after staining with alcian blue (AB). Although histamine content and distribution in GP and human heart appeared to be different, morphological and histochemical studies of MC suggested a similarity between the two species and a clear distinction from rat peritoneal MC.     

Immunological phenotypic pattern of acute lymphoblastic leukaemia in Egypt

We have performed immunophenotyping studies on 186 untreated cases of acute lymphoblastic leukemia (ALL) in an Egyptian population, using panels of monoclonal antibodies (mAb) and an avidin-biotin-immunoperoxidase detection system. Sixty-two of these cases were tested with a panel of mAb directed against the T-cell markers CD2, CD4, CD8, B-cell markers CD20, kappa and lambda, the common ALL antigen (common ALLa) and class II HLA antigens. The remaining 124 cases were also tested with additional markers of T- and B-cell precursors, namely CD7 and CD19. The common leukocyte antigen, T200, was used to exclude nonhemopoietic neoplasms. Cases that remained unclassifiable were further tested with a wider panel of T-cell markers, including CD1, CD2, CD3 and CD5. In some cases multiple mAb directed against the same antigens were used. The relative frequencies of common ALL and B ALL were calculated from the total number of cases and were found to be 39.2% and 3.2%, respectively. The proportions of T-cell and null leukemias were calculated from the better characterized subgroup of 124 cases, and were found to be 50% and 4.8%, respectively. In our series, the age distribution of common ALL revealed a peak at 2-5 yr, but this was partially obscured in the entire series by the high proportion of T-cell cases, which had an age peak between 4 and 12 yr of age. Our results demonstrate marked differences in the phenotypic pattern of ALL in Egypt compared to Western Countries, the predominant finding being a relative excess of T-cell ALL and a paucity of common ALL cases. At present it is not clear whether this results from an increased incidence of T-cell ALL or a decreased incidence of common ALL.     

A modified radioimmunoassay for the detection of histamine release in vivo and in vitro in man.

Histamine (Hi) release in vitro or in vivo in man was measured by variants of a radioimmunoassay (RIA) procedure. Hi released from isolated basophils was converted enzymically to N-tau-methylhistamine (NMH) which was then measured by a very sensitive RIA. This modified RIA was compared with the standard spectrofluorometric assay and was found to have additional advantages in certain applications. RIA of NMH in plasma was found to be of value in acute medical conditions of obscure aetiology.     

Anti-allergic properties of cyclosporin A: inhibition of mediator release from human basophils and rat basophilic leukemia cells (RBL-2H3).

In vitro the immunosuppressive drug cyclosporin A (CS-A) strongly inhibited histamine release from human basophils (HB) and the rat basophilic leukemia cell line (RBL) 2H3. It also inhibited leukotriene release from HB. In HB the IC50 values for inhibition of histamine release induced by Con A, anti-IgE, calcium ionophore A23187 and antigen (mite) were 0.03, 0.12, 0.36 and 2.0 microM, respectively. In fact, these figures underestimate the potency of CS-A, since studies with 3H-CS-A showed substantial adsorption to plastic experimental wares which was inversely proportional to drug concentration. With anti-IgE and A23187, the drug acted promptly when added at the same time as the inducers but, with antigen, inhibition increased with time of pre-incubation. Washing of HB after pre-incubation with CS-A did not remove the drug effect. Inhibition of histamine release was abolished by Ca2+ excess (5 mM). For TPA-induced release, the drug inhibited the Ca2(+)-dependent but not the Ca2(+)-independent component. In Ca2(+)-free conditions, ionophore A23187, which caused little or no histamine release on its own, was able to synergize with TPA in causing release, apparently by mobilizing intracellular Ca2+. CS-A blocked the synergism but not the original TPA effect. CS-A was compared with the calmodulin inhibitors, W7, TFP and ABCNS; all inhibited histamine release. CS-A also potently inhibited IgE-mediated histamine release from RBL-2H3 cells, without affecting their growth or viability.     

Effect of sympathomimetic amines on the histamine forming capacity of human leucocytes

1 The effects of alpha- and beta-adrenoceptor stimulants on the histamine-forming capacity (HFC) of human isolated leucocytes have been studied, in vitro.2 It was confirmed that antigen significantly stimulates the HFC of human leucocytes.3 beta-Adrenoceptor stimulants, such as isoprenaline and salbutamol (10(-6)-10(-3)M) significantly inhibited the HFC of human leucocytes in the presence and absence of antigen. At concentrations lower than 10(-6)M, this effect was not observed. In general the degree of inhibition of HFC by beta-adrenoceptor stimulants followed their potency as beta-adrenoceptor stimulants.4 alpha-Adrenoceptor stimulants significantly stimulated leucocyte HFC; noradrenaline within a limited concentration of 10(-6)M, while stimulation was seen consistently with phenylephrine at concentrations of 10(-7)-10(-4)M. Adrenaline, which stimulates both alpha- and beta-adrenoceptors, produced small inhibition, no effect, or a degree of stimulation.5 Phentolamine, an alpha-adrenoceptor blocking agent, produced an effect opposite to that of the alpha-adrenoceptor stimulants, i.e. a significant inhibition of the HFC of human isolated leucocytes.     

Cryptogenic pulmonary eosinophilia.

The clinical and immunological features of fifteen cases of cryptogenic pulmonary eosinophilia are reported. There were ten women (mean age 35.4 years) and five men (mean age 42 years). Eight gave a previous history of asthma and seven had none. Thirteen of the fifteen patients had negative skin test to common allergens. Many features of a systemic illness were present in the asthmatic and non-asthmatic groups including anaemia, weight loss, fever and a grossly raised ESR. An absolute polymorphonuclear leucocytosis was frequent as well as the obligatory increase in blood eosinophils used as one of our criteria for inclusion. Hepatomegaly (three cases), splenomegaly (four cases) and hilar node enlargement (one case) were seen in the group without asthma. Evidence of renal involvement or necrotizing vasculitis was notably absent and the response to small doses of corticosteroids was dramatic. Immunologically the striking feature was a disproportionate increase in blood eosinophils compared with only minor elevations in the total serum IgE levels. This stands in contrast to patients with bronchopulmonary aspergillosis and helminth infestation. Studies of cytophilic antibodies using histamine liberation after challenge with antibodies to immunoglobulin sub-classes in six patients showed a marked increase in IgG2 and lesser increases of IgE and IgG3. No evidence of antibodies specific to A. fumigatus was found. The amount of cytophilic antibody was also in contrast to that found in bronchopulmonary aspergillosis.