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Biomedical subjects

J L Beets

Publications and source records attributed to J L Beets.

8 recordsLinked to original sources

Inhibition of human lymphocyte transformation as an in vitro parallel line bioassay for anti-human lymphocyte globulin.

Horse anti-human lymphocyte globulin (HALG) is now widely clinically, but the variable immunosuppressive potency of different preparations of HALG has necessitated development of an accurate, reproducible in vitro assay of HALG potency. Currently available tests have several disadvantages, as well as showing little correlation with in vivo activity of the preparations tested. Incorporation of tritiated thymidine into lymphocytes, stimulated with mitogen (PHA) or antigen (PPD) and the inhibition of this process by HALG is described. ID50S and potency ratios have been determined for four HALG preparations. The ID50S obtained with these preparations were reproducible and the potency ratios obtained using 3 + 3 parallel line bioassay were similarly reproducible, a change in rank order being observed only once in ten assays. These in vitro results correlate with in vivo skin graft data. It is suggested that this technique could be used for evaluation of HALG preparations on peripheral blood from potential recipients.

Animals

The gastrointestinal absorption of PRD-92 Ea, a new anti-allergy drug.

1 The absorption of PRD-92 Ea, a new anti-allergy drug, was studied in volunteer subjects. 2 The 14C-labelled drug was administered orally and the radioactivity measured in plasma, urine and faeces. 3 Mean peak plasma concentration was 3.3 micrograms/ml, with a concentration of over 1 micrograms/ml maintained 4 h after administration. 4 The mean plasma half-life (T 1/2) was 114 min. 5 The mean percentage recovery in the urine was 9.5%. 6 Oral administration leads to significant and sustained plasma concentrations, and the oral route should be suitable for drug evaluation in clinical practice.

Adult

Inhibition of guinea-pig lymphocyte activation by histamine and histamine analogues.

1 The incorporation of [3H]-thymidine into guinea-pig lymphocytes stimulated by a plant lectin (concanavalin A), soluble antigen (tuberculin (P.P.D.)) and syngeneic hepatoma cells, was partially inhibited (50%) by histamine in vitro. 2 The effect of histamine on both mitogen and antigen dose-response curves suggests a non-competitive, probably physiological antagonism. 3 The inhibitory dose range of histamine lay between 10 nM and 30 microM with an ID50 of approximately 400 nM. 4 The potency order for histamine analogues for the inhibition of lymphocyte activation was histamine greater than or equal to 4-methylhistamine greater than 2-methylhistamine greater than 3-methylhistamine. This is in accord with the mediation of the response through an H2-receptor. 5 H2-receptor antagonists reversed the inhibitory effect of histamine in a dose-related manner, but both metiamide and burimamide, in high concentrations, augmented lymphocyte activation in their own right. This precluded the determination of affinity constants and made it impossible to state with certainty that the inhibition of lymphocyte activation by histamine was mediated by an H2-receptor.

Animals

Anti-inflammatory drug actions on allergic responses in guinea-pig skin.

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.

Animals