Hypodipsic hypernatremia with normal osmoregulation of vasopressin.
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Biomedical subjects
Publications and source records attributed to E Chelmicka-Schorr.
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C-6 glioma cells possess beta-adrenergic receptors on the cell surface. Activation of beta-adrenergic receptors with beta-adrenergic agonists increases intracellular levels of cAMP and leads to differentiation of C-6 glioma cells in vitro. The present study shows that growth of C-6 glioma tumor in rats with ablated sympathetic nervous system is augmented as compared to controls. Lack of normal noradrenergic stimulation of C-6 glioma cells may lower intracellular cAMP and allow unrestricted growth of this tumor.
The sympathetic nervous system modulates the growth of C-1300 mouse neuroblastoma in vivo and in vitro. We now report that a mitogenic/trophic factor that augments growth of C-1300 neuroblastoma and of the S-20 neuroblastoma clonal line is present in freshly excised sympathetic cervical ganglia from newborn rats, but is not detectable in homogenates from sympathetic ganglia obtained from adult rats.
The sympathetic nervous system modulates the growth of C-1300 mouse neuroblastoma (C-1300 NB) in vivo. We now report that the presence of sympathetic cervical ganglia in cultures containing C-1300 NB or dispersed S-20 neuroblastoma (S-20 NB) cells augments growth of these tumors in vitro. Sympathetic ganglia-conditioned medium increases proliferation and survival of S-20 NB cells, indicating that nervous system-derived growth factors can exert an effect on neoplastic cells.
Ablation of the peripheral sympathetic nervous system by treatment of adult (axotomy) and neonatal (sympathectomy) mice with 6-hydroxydopamine hydrobromide produced significant changes in the distribution of cell surface molecules detected on spleen lymphocyte populations. The surface molecules that were studied consisted of the beta-adrenergic receptor and the Thy-1.2 and Lyt-2 surface antigens associated with lymphocyte subpopulations. beta-Adrenergic receptor density, as measured by 3H-dihydroalprenolol binding, was found to be significantly higher on control mouse splenic B cells than on T cells. beta-Adrenergic receptor density was seen to increase in both T and B spleen cell populations after axotomy. The Thy-1.2 and Lyt-2 surface antigens present on cell populations from mouse spleens were labeled using fluorescent monoclonal antibodies and quantitated using a fluorescence-activated cell sorter. A significant increase in the percentage of Thy-1.2 positive cells represented among the total spleen lymphocyte population was detected in axotomized mice. A corresponding increase in the representation of Lyt-2-positive cells, a subset of the Thy-1.2-positive population, was also found. In contrast, while the percentage of Thy-1.2-positive cells per total spleen lymphocyte population were not found to differ between control and sympathectomized mice, a significantly lower percentage of Lyt-2 positive cells within the Thy-1.2-positive population appeared in sympathectomized mice. Suppressor/cytotoxic cell function, as well as properties relating to the recognition of major histocompatibility complex antigens, have been associated with the Lyt-2 antigen. The relative distributions of lymphocyte subpopulations, as indicated by surface markers, and their beta-adrenergic receptors may play an important role in the physiologic functions and interactions between lymphocytes that respond to sympathetic nervous system innervation.
The sympathetic nervous system exerts a trophic-mitogenic influence on C-1300 mouse neuroblastoma. We now report that sympathetic axotomy suppresses growth of the S-20 clonal line of neuroblastoma but does not influence the growth in vivo of two other clonal lines, NIE-115 and C-46. Sympathetic ganglia-conditioned medium significantly increases proliferation of S-20 cells in vitro. Growth of NIE-115 and C-46 clonal neuroblastoma lines is not influenced by sympathetic ganglia-conditioned medium. We postulate that the sympathetic nervous system secretes a mitogenic-trophic factor that favors growth of C-1300 neuroblastoma in vivo. Sensitivity to this factor varies between neuroblastoma clonal lines.
Rat C-6 glioma serves as an experimental model for human glioma. C-6 glioma cells carried to high culture passages in medium containing 10% fetal bovine serum when injected in vivo are unresponsive to treatment with the beta-adrenergic agonist isoproterenol and the phosphodiesterase inhibitor papaverine. When C-6 glioma cells are kept in culture in serum-containing medium, beta-adrenergic receptor density falls and, concomitantly, ability to accumulate cyclic adenosine monophosphate in response to stimulation with catecholamines declines. Responsiveness to treatment in vivo with a beta-adrenergic agonist was restored when C-6 glioma cells were cultured in serum-free defined medium prior to systemic injection into rats. Culturing of C-6 glioma cells in serum-free medium significantly increases the number of beta-adrenergic receptors when compared with C-6 glioma cells grown in serum-containing medium.
Adrenergic receptors are present on lymphocytes but the extent to which their activation modulates lymphocyte function remains unclear. We studied beta-adrenergic receptors on mouse spleen lymphocytes using the antagonist 3H-dihydroalprenolol (3H-DHA) as a specific ligand. We report a significant increase in beta-receptor density in spleen lymphocytes from mice treated with 6-hydroxydopamine (6-OHDA) to destroy peripheral sympathetic nerve endings (axotomy). Mouse spleen lymphocytes were separated into T and B subpopulations on nylon wool columns or by panning. B cells from both control and axotomized mice were found to bear twice as many beta-receptors as T lymphocytes. Finally, using flow cytometry to identify cells labeled with goat anti-mouse immunoglobulin (lg), axotomized mouse spleen lymphocyte populations were shown to contain 25% fewer B cells than controls. This work demonstrates differences in beta-adrenergic receptor density on functionally distinct populations of lymphocytes. Furthermore, we show adaptive changes in receptor density on T and B lymphocytes following sympathetic denervation. Both of these observations serve to link the immune and sympathetic nervous system in a regulatory network.
The adrenergic blocking agent methyldopa (Aldomet) is toxic to C-1300 neuroblastoma cells in vivo. Four injections of Aldomet at a dose of 7.5 mg/injection were given over a period of 24 hr to C-1300 neuroblastoma-bearing mice. This treatment killed a significant proportion of the C-1300 neuroblastoma cells. Flow cytometric data suggest that sensitivity of tumor cells to Aldomet is not related to the cell cycle.
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Acid protease activity was increased in skeletal muscle of patients with ALS. The highest levels of activity were found in individuals with the clinically and histologically most affected muscle. High levels of proteolytic activity correlated with the extent of muscle atrophy, the presence of target fibers and the overall severity of disease.
Sympathetic nerve endings were destroyed with 6-hydroxydopamine (6-OHDA) and the response to thymus-dependent and -independent antigens compared in 6-OHDA-treated and control mice. A significantly enhanced plaque-forming cell response to 2 thymus-independent antigens was observed in the 6-OHDA-treated mice; in contrast the response to a thymus-dependent antigen was normal. The findings point to selective modulation of antibody response by the sympathetic nervous system.
Rat C-6 glioma possesses a beta-adrenergic receptor which, when activated, raises intracellular levels of cyclic adenosine monophosphate (cAMP) in cultured C-6 glioma cells. The present study shows that growth of C-6 glioma is suppressed in rats treated with the beta-adrenergic agonist isoproterenol. Addition of papaverine, a cAMP phosphodiesterase inhibitor, to the treatment schedule augments this effect. Pharmacological agents that elevate intracellular cAMP levels may retard the growth of neural tumors in vivo.
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A girl with Eaton-Lambert syndrome had symptoms beginning at the age of 9 years. An extensive search for underlying neoplasm or definable autoimmune disease gave negative findings.
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Growth of C-1300 neuroblastoma was markedly suppressed in mice chemically sympathectomized at birth with 6-hydroxydopamine. Growth of A-10 adenocarcinoma was also somewhat reduced. In newborn mice pretreated with nerve growth factor to induce sympathetic nervous system neuronal hypertrophy, neuronal maturation, and peripheral hyperinnervation, the growth of neuroblastoma was augmented.