Suppression of sprouting at the neuromuscular junction by immune sera

Injury of afferent motor axons or pathological loss of motoneurones from the spinal cord causes the remaining axons within a muscle to sprout and to reinnervate the denervated muscle fibres. Sprouting occurs at two sites along intramuscular axons, at nodes of Ranvier (nodal sprouting) and at the neuromuscular junction (terminal sprouting). Terminal sprouting is also produced by treatment with botulinum toxin and by other agents that render muscle inactive. The muscle probably provides a signal for terminal sprouting as restoration of muscle activity by direct electrical stimulation prevents sprouting. Such a signal might be a local change on the muscle fibre surface or a 'soluble' sprouting factor, although the failure to induce terminal sprouting in one muscle by denervating adjacent muscles argues against the latter hypothesis. I now report that rabbit antisera against a 56,000 (56K)-molecular weight protein secreted by denervated rat muscle suppress botulinum toxin-induced terminal sprouting in the mouse gluteus muscle. An immune response against this protein has also been detected in serum of patients with amyotrophic lateral sclerosis (ALS), a disease in which loss of motoneurones from the spinal cord is not accompanied by the degree of sprouting and reinnervation seen in other motoneurone diseases.     

Endogenous mammary tumour virus DNA varies among wild mice and segregates during inbreeding.

Proviruses of the mouse mammary tumour virus (MMTV) endogenous to normal mice can be identified by molecular hybridisation and distinguished using restriction endonucleases. Feral mice display marked heterogeneity with respect to the number of copies and the sites of insertion of endogenous MMTV-specific DNA, with occasional mice apparently free of MMTV DNA. Several different MMTV proviruses present in laboratory mice have segregated like stable, independent genetic elements during the inbreeding which followed a cross between Bagg albino and DBA mice 60 years ago. The results favour the hypothesis that endogenous proviruses have been established by multiple, independent infections of germ cells rather than by somatic mutation of ancestral proviruses or of cellular genes.     

Evidence that three structural genes code for human alkaline phosphatases.

The number of structural gene loci that code for the different molecular forms of human alkaline phosphatase is unknown. Physical properties of the enzymes, immunological data, chemical inhibition and genetic studies suggest that at least three structural genes are involved: one coding for alkaline phosphatase from placenta, another for the enzyme from intestine, and one or more for the enzymes from liver, kidney and bone. Badger and Sussman have shown that alkaline phosphatases from human liver and placenta are products of different structural genes, and Greene and Sussman have shown that alkaline phosphatase from a metastasised bronchogenic carcinoma was nearly identical to the enzyme from placenta. However, other tumour-associated alkaline phosphatases and the enzymes from normal tissue other than placenta and liver have not been identified by conclusive structural criteria, and thus it is not known whether these onco-alkaline phosphatases represent ectopic production or unusual post-translational modification of the enzymes found in normal tissues. We present here, using a sensitive peptide-mapping technique, structural evidence that the enzyme forms from liver, kidney and serum from a patient with Paget's disease of bone (osteitis deformans) are products of the same structural gene and can be easily distinguished from either the intestinal or placental isoenzymes. The technqiue seems to be useful for the classification of tumour-associated alkaline phosphatases on a structural basis.     

Bombesin suppresses feeding in rats.

Bombesin (BBS) is a tetradecapeptide originally isolated from amphibian skin1. BBS-like immunoactivity is widely distributed in mammalian gut2-5, and plasma levels have been shown to rise sharply following feeding (ref. 6 and V. Erspamer, personal communication). The physiological actions of BBS are unknown. We have previously shown that the classic gut hormone cholecystokinin (CCK) is a powerful and specific suppressor of food intake7-9. Although CCK and BBS lack common amino acid sequences, they have certain common actions on gut viscera10,11. We have now shown that BBS also suppresses food intake, and we compare its action with that of CCK.     

An independent microbial flora of the epithelium and its role in the ecomicrobiology of the rumen

IT has been suggested that the bacterial flora of the rumen should be considered as three distinct, interacting populations-the bacteria of rumen fluid (the population which has been studied most extensively), the bacteria associated with food particles, and the bacteria adhering to the epithelial wall of the organ(1). Until now, studies of the 'epithelial' population have been restricted to examination of postmortem samples of wall tissue and its attached bacterial flora(2-5). A recently developed technique(6) for feeding young sheep for long periods solely by infusion of protein and other essential nutrients into the abomasum, and of volatile fatty acids and bicarbonate buffer into the rumen, has provided us with an opportunity to study in isolation the role of the bacterial population of the wall in the ecomicrobiology of the rumen in the living animal. Our studies show that this population can exist independently of the other two populations, that it is primarily responsible for urea digestion in the rumen and that it initiates breakdown of dead epithelial tissue. Furthermore, our results point to an inverse relationship between ammonia concentration and ureolytic activity in rumen fluid, which may account for the control which ammonia exerts over flux of urea across the rumen wall(7-9).     

Agonist-induced potentiation of acetylcholine sensitivity in denervated skeletal muscle

The entire surface membrane of denervated skeletal muscle is sensitive to the neuromuscular transmitter, acetylcholine (ACh), whereas in innervated muscle only the junctional area is sensitive. It has been proposed that this difference is due to a 'trophic' effect exerted by ACh in innervated muscle to keep the extrajunctional regions of the surface membrane insensitive to its depolarising action. Several studies have demonstrated an agonist-induced potentiation of ACh sensitivity, followed by desensitisation, at the endplate region of normal muscles. The potentiation has been attributed to a cooperative action of ACh on the receptors. Desensitisation of the extrajunctional regions of denervated muscles by ACh has also been described. We now provide evidence that the transmitter itself potentiates the ACh contracture and depolarisation responses of the denervated muscles of the rat in vitro and that it produces this effect by increasing the number of available ACh receptors on the surface membrane.