Immunological and morphological consequences of vasectomy in the rabbit

Summary Cell-mediated immunity to spermatozoa was detected in vitro 6–18 months after vasectomy in the rabbit. The autoimmunity was accompanied by aspermatogenic orchitis in the testes and epididymides.Acknowledgments. We acknowledge the financial support of the Australian Research Grants Committee and the Australian and Kenyan Governments for support through the Australian Development Assistance Bureau.     

The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase

Colony stimulating factor-1 (CSF-1) is a lineage-specific growth factor required for proliferation and survival of mononuclear phagocytes and their precursors. The CSF-1 receptor belongs to a family of ligand-activated protein-tyrosine kinases. Activation of the platelet-derived growth factor receptor, but not the CSF-1 receptor, leads to an increase in phospholipase C activity and a subsequent elevation in intracellular calcium. Recent studies have shown that a novel phosphoinositol (PtdIns) kinase, termed PtdIns-3 kinase, is stimulated by the platelet-derived growth factor receptor and certain oncogenes in the protein-tyrosine kinase family. PtdIns-3 kinase phosphorylates the D-3 hydroxyl position of the inositol ring of PtdIns, and its products do not participate in the generation of the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). Here we report that addition of CSF-1 is followed by activation of PtdIns-3 kinase in a macrophage cell line (P388 D1), which contains CSF-1 receptors, and in BALB/c fibroblasts made to express the human CSF-1 receptor. Furthermore, we show that activation of the CSF-1 receptor results in the accumulation in intact cells of polyphosphoinositides phosphorylated at the D-3 position of the inositol ring. Thus activation of the CSF-1 receptor stimulates PtdIns-3 kinase activity, indicating a novel pathway for CSF-1 receptor-mediated signal transduction.     

Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins

Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.     

Acetylcholine contributes through muscarinic receptors to attentional modulation in V1

Attention exerts a strong influence over neuronal processing in cortical areas. It selectively increases firing rates and affects tuning properties, including changing receptive field locations and sizes. Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca mulatta) performed a task that demanded top-down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1.