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Biomedical subjects

I R Smith

Publications and source records attributed to I R Smith.

29 records · Page 2Linked to original sources
PubMed1982

The limited fragmentation of porcine haemolytic immunoglobulin M. Evidence that haemolytic activity depends on the number of Fab arms that can attach to the erythrocyte surface.

Methods previously developed in this laboratory for the proteolytic removal of limited numbers of Fab arms from the IgM molecule have been used to study haemolytic activity. The gradual removal of arms produced a rapid decrease in complement-mediated lysis of erythrocytes but had a much slower effect on their agglutination. Therefore a stage was reached at which molecules with four Fab arms gave good agglutination but did not cause cell lysis. The same result was obtained whether Fab arms were removed randomly by pepsin or in pairs by trypsin. Hence the non-lytic nature of these molecules was independent of the arrangement of their remaining Fab arms. A sharp decrease in haemolytic activity was also obtained under conditions of high antibody concentration when the IgM molecular could attach only a few of its Fab arms to the erythrocyte surface. Possible explanations for the dependence of haemolytic activity on the number of Fab arms discussed.

Animals↗
PubMed1981

Histamine release from human right atrium.

Histamine release has been detected biologically after exposure of human right atrial biopsy samples to compound 48/80. Human right atrial samples contain large quantities of histamine, 1035 +/- 65 ng/g fresh weight. Exposure of untreated electrically paced atrial strips to compound 84/80, 300 micro/ml, caused an increase in the force of atrial contraction similar to that caused by histamine. Pretreatment of strips with cimetidine, 3.16 x 10(-5) M, prevented the inotropic response to compound 48/80. It is concluded that mast cell degranulation in human atrial tissue can cause sufficient release of histamine to modify the function of the heart.

Heart Atria↗
PubMed1980

Uptake and metabolism of histamine in guinea-pig isolated atria and their relationship to the pharmacological responses.

1. The uptake of radiolabelled 14C-histamine into guinea-pig isolated left atria was determined. 2. Mepyramine up to 10(-7) M had no significant effect upon the uptake of total radioactivity. Metiamide (10(-4) M) produced a small but not significant inhibition of uptake. SK & F 91581 (10(-4) M) and amodiaquine (10(-4) M) both significantly inhibited uptake by 48.2 +/- 4.2 and 56.7 +/- 1.2% respectively. 3. The metabolism profiles of radiolabelled histamine after 5 and 30 min incubation were examined by thin-layer chromatography. 4. SK & F 91581 (10(-4) M) and amodiaquine (10(-4) M) reduced the proportion of N tau-methylhistamine and acid metabolites after a 30 min incubation. The levels of unmetabolized histamine were elevated. This may explain their inhibitory action upon histamine uptake. 5. The effects of mepyramine, metiamide, SK & F 91581 and amodiaquine were then examined upon the positive inotropic and chronotropic responses of isolated left and right atria to histamine. 6. Mepyramine (10(-7) M) inhibited the positive inotropic responses only (H1), whereas metiamide (10(-4) M) inhibited the positive chronotropic responses only (H2). SK & F 91581 (10(-4) M) had no effect upon these responses and amodiaquine (10(-5) M) depressed the maxima of the rate response dose-response curves. 7. The relationship between uptake and metabolism of histamine and its pharmacological response is discussed.

Amodiaquine↗
PubMed1980

Binding of [3H]cimetidine to rat brain tissue.

Binding of [3H]cimetidine to rat brain tissue was investigated, and a saturable binding with dissociation constant 0.22 +/- 0.05 microM found. This binding is inhibited by a range of imidazole-derived histamine H2-receptor antagonists, but not by a number of non-imidazole H2-receptor antagonists. It is concluded that the [3H]cimetidine binding site in rat brain tissue that is labelled in these experiments is not the histamine H2-receptor.

Animals↗