The decision of a clinician to treat or not to treat a particular hypertensive patient with hypotensive drugs shall be based on the health status of this patient and on data derived from different sources; the latter can be grouped into two major categories: epidemiological studies and intervention trials.

Transforming growth factor, type β (TGF-β) was first described by its ability to stimulate mouse embryo-derived AKR-2B cells (Moses et al. 1981) and rat NRK cells to grow in soft agar (Roberts et al. 1981). (The latter cells also required the addition of epidermal growth factor, EGF.) Subsequent studies have shown that TGF-β functions as a growth stimulator only for certain fibroblastic cells, possibly through an indirect mechanism involving the induction of endogenous growth-factor synthesis resulting in autocrine growth (Leof et al. 1986). In fact, TGF-β is a growth inhibitor for most cell types tested (Moses et al. 1985a and unpublished observations). Its growth-inhibitory properties, or those of a closely related molecule, were described by Holley and co-workers several years before its growth-stimulatory effects were discovered (Holley et al. 1978; Tucker et al. 1984a). This review discusses the possible mechanism of growth stimulation and growth inhibition by TGF-β and the possible role of this factor in neoplastic transformation.

Summary

The axoplasm of nodes of Ranvier in feline lumbosacral ventral spinal roots was analysed by light and electron microscopy 18–168 h after the injection of horseradish peroxidase (HRP) into the medial gastrocnemius muscle. Three main HRP distribution patterns were distinguished at PNS nodes (bordered by Schwann cells only) of large fibres transporting HRP. (1) Thetype A pattern, characterized by a distal accumulation of HRP-positive bodies and a proximal system of vesiculotubular membrane profiles. The incidence of this type of node was highest at relatively short survival times. (2) Thetype B pattern, which appeared somewhat later, resembled the type A node with the addition of a disc-like, proximal accumulation of HRP activity. (3) Thetype C pattern which contained scattered HRP-positive bodies and delicate strands of membraneous profiles, dominated 72 h after injection.

The number of HRP-positive PNS-CNS borderline nodes (bordered by both Schwann cells and glial cells) was less than 5% of the corresponding value in the same fibres of the ventral root proper. A highly segregated state of the axoplasm of PNS-CNS borderline nodes was noted only in two cases. The observations indicate a functional difference between nodal axoplasm at the PNS-CNS borderline and nodal axoplasm in the PNS part of the alpha motor neuron.

Following activationin vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2Rin vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a “sandwich” enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4⁺) cells and OKT4-negative (OKT4⁻) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL-2R were released by PBMC, unseparated T cells, OKT4⁺ T cells, and OKT4⁻ T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated withStaphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2Rin vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4⁺ and OKT4⁻ T-cell subsets.

Summary

The rate of unstimulated influx of Ca²⁺ into rat aorta smooth muscle, measured as uptake of ⁴⁵Ca, was inhibited in the presence of endothelium as compared to influx in the absence of endothelium. Efflux of ⁴⁵Ca from unstimulated prelabelled tissues was also reduced in the presence of endothelium. In normal physiological solution the rate of influx and efflux of Ca²⁺ stimulated by B-HT 920 (1 and 10 μM), but not that stimulated by phenylephrine (30 nM and 1 μM), was also reduced in the presence of endothelium. In the presence of the calcium entry blocker flunarizine (3 μM), phenylephrine (1 μM) stimulated efflux of Ca²⁺ was inhibited by the presence of endothelium. A correlation between inhibition of Ca²⁺ influx and modulation of α-adrenoceptor agonist-induced contractions by endothelium could not be demonstrated, and methylene blue, an antagonist of endothelium mediated inhibition of B-HT 920 contractions, did not affect Ca²⁺ influx stimulated by the agonist. The effects of endothelium on Ca²⁺ influx and efflux are unlikely to be due to alterations by endothelium of diffusion of ⁴⁵Ca or the agonists in the vessel. The results demonstrate that an endothelial derived factor or factors can reduce calcium influx into smooth muscle cells and also modulate the release of calcium from cells, perhaps by affecting intracellular calcium pumping mechanisms. A reduction of calcium influx cannot be the sole explanation for the modulatory effect of endothelium on α-adrenoceptor agonist-induced contractions but an effect on intracellular calcium metabolism may be important.

LG 30435 is a quaternary phenothiazinic antihistamine, endowed with bronchodilator and antiallergic activity. Since PAF-acether (PAF) is a potential mediator of asthma, LG 30435 was assayed for its ability to counteract PAF-induced platelet aggregation (PA) in rabbit platelet rich plasma and bronchoconstriction (BC) in anaesthetized guinea-pigs, in comparison with other antihistamines. LG 30435 was the most potent and selective inhibitor of PAF-induced PA (IC₅₀∶66 μM), concentrations three and more than fifteen fold higher being needed to inhibit PA induced by collagen and arachidonic acid respectively. The other antihistamines, namely mepyramine, promethazine, mequitazine, thiazinamium methyl sulfate and ketotifen were less potent inhibitors of PAF-induced PA, while interfered at lower concentrations with collagen-induced PA. LG 30435 and thiazinamium, administered intravenously, inhibited dose-dependently PAF-induced BC, starting from the dose of 0.1 μmol/kg. The travenously, inhibited dose-dependently PAF-induced BC, starting from the dose of 0.1 μmol/kg. The ED₅₀ of LG 30435 was 0.28 μmol/kg, while the inhibition obtained with thiazinamium did not reach 50% even at 3 μmol/kg. Ketotifen and promethazine were partially active only at 3 μmol/kg, while mequitazine and mepyramine were inactive up to this dose. These results show that LG 30435 is endowed with a peculiar anti-PAF action, which may be advantageous in the treatment of asthma.

Summary

The kinetics of phenobarbital (PB) was compared after oral administration of equivalent doses of the drug as the acid or the propylhexedrine salt (barbexaclone) to 7 normal volunteers. The absorption and elimination parameters were very similar. It was concluded that propylhexedrine did not affect the serum kinetics of PB given as barbexaclone.

Originally the inspiration for this book stemmed from a Symposium on Enkephalins; Endorphins: Stress and the Immune System held at the Annual meeting of the American Society of Pharmacology and Experimental Therapeutics in Philadelphia 1983. Since that meeting a significant increase in research has occurred and prompted us to compile this book. Recent research has shown that the immune system is exceedingly sensitive to the effects of enkephalins and endorphins. This sensitivity was illustrated by the immunodepressant effects of morphine on T-cells. In contrast the enkephalins and endorphins have shown to enhance T-cell function.

Injection of pristane (2,6,10,14 tetramethylpentadecane) into the peritoneal cavity of Balb/c mice has been used to induce plasmacytomas (1) and to induce a microenvironment that will support the growth of transplanted plasmacytomas derived from primary hosts (2) and B-cell hybridomas (3). In vitro growth of primary plasmacytomas (4) and B-cell hybrids immediately after fusion (5) requires the addition of “feeder” cells to the culture medium. In previous studies we have shown that this feeder-cell requirement of B-cell hybrids can be overcome by the addition of the supernatant of human endothelial cell cultures to the culture medium (6,7). The characterization of this growth-promoting activity has been hampered by the lack of rapid and reproducible assay.