Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ion selectivity of the Ca2+ channels in single ventricular cells of guinea-pig was studied using a 'giga-ohm seal' patch electrode for voltage clamp and internal dialysis. To isolate the Ca2+ channel current, currents through the Na+ channel and K+ channels were minimized by replacing external Na+ with Tris+ and removing K+ from both sides of the membrane. With 5 mM-ATP and 5 mM-EGTA in the pipette solution, the Ca2+ current was well maintained for more than 30 min in K+- and/or Na+-free external solution. Substitution of Cs+ for intracellular K+ eliminated the region of negative slope conductance in the steady-state current-voltage curve and shifted the zero-current potential or resting potential from -80 to -31 mV. After Cs+ substitution, a large inward current still flowed via inwardly rectifying K+ channels, but was abolished by removing external K+, which resulted in reduction of the resting membrane slope conductance to 1% of the control value. A decaying outward current attributable to the inwardly rectifying K+ channel was observed on depolarization in 5.4 mM-external K+ solution with Cs+-rich internal solution after blocking Ca2+ current. The induction of that current caused an apparent decrease of Ca2+ channel current when the K+-rich internal solution was switched to the Cs+-rich one at an external K+ concentration of 5.4 mM. When inwardly rectifying K+ current was suppressed by exposure to K+-free external solution, replacement of intracellular K+ with Cs+ caused no significant change in the Ca2+ current. With Cs+-rich solution in the electrode, the decaying outward current was responsible for an apparent depression of the Ca2+ current observed when extracellular K+ was increased. When the K+ current was abolished by 0.2 mM-extracellular Ba2+, changes in external K+ concentration did not affect the Ca2+ current, excluding the possibility of a direct inhibitory action of K+ on the Ca2+ channel. A time- and voltage-dependent outward current attributed to Cs+ was observed at potentials above +30 mV in Na+-, K+-free external solution with Cs+-rich internal solution. This current persisted in the presence of 20 mM-intracellular TEA Cl and 5 mM-extracellular 4-aminopyridine. Inorganic Ca2+ channel blockers, such as Co2+ or Cd2+, not only suppressed the inward Ca2+ current but also caused some reduction in outward current. Thus the blocker-sensitive peak current reversed at around +75 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Isolation of calcium current and its sensitivity to monovalent cations in dialysed ventricular cells of guinea-pig. 609 35

Incubation of neuronal cell bodies in a calcium-free medium depresses the amount, but not the rate, of fast axonal transport of [3H]protein. Under these conditions, which do not affect protein synthesis or general energy metabolism, less protein appears to be loaded onto the transport system. Depression of transport also is seen when cell bodies are exposed to medium containing Co2+; selective exposure of axons to this medium has no effect on transport. These findings have led to the concept of an initiation phase of fast axonal transport that comprises the events by which selected proteins are transferred from their polysomal sites of synthesis to the transport system. The divalent cation specificity of the Ca2+ requirement, and its occurrence subsequent to Golgi apparatus-associated glycosylation, suggest that proteins destined for fast axonal transport are routed through the soma in a manner similar to that of secretory proteins and integral membrane proteins in nonneural cells. This analogy is pursued to consider a scheme whereby Golgi-derived vesicles deliver fast-transported proteins to the axonal smooth endoplasmic reticulum. Possible roles of Ca2+ in the formation and exocytotic fusion of such vesicles are considered.
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PMID:The role of calcium in the initiation of fast axonal transport. 615 71

The influence of various 5-hydroxytryptaminergic agonist and antagonist drugs on body-temperature response to cobaltous chloride in mice was noted. Pretreatment with p-chloroamphetamine, p-chlorophenylalanine, and p-iodoamphetamine antagonized the body-temperature response to cobalt. p-Chloroamphetamine and p-chlorophenylalanine reduced, while p-iodoamphetamine elevated, brain serotonin levels. The uptake inhibitor agents, fluoxetine and nisoxetine, failed to modify the ability of p-chloroamphetamine to antagonize cobalt hypothermia. Cyproheptadine, methergoline, and xylamidine pretreatment enhanced rather than antagonized body-temperature depression by cobalt. Tryptophan hydroxylase inhibitors antagonized cobalt hypothermia, but receptor-blocking agents were without influence, indicating that antagonism was mediated through mechanisms other than the depletion of serotonin. Elevation rather than depletion of brain serotonin by p-iodoamphetamine and failure of uptake inhibitors to modify p-chloroamphetamine antagonism of cobalt hypothermia lend further support for a nonserotonergic role of these amines in their ability to antagonize body-temperature depression by cobaltous chloride in mice.
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PMID:Cobaltous chloride-induced hypothermia in mice III: effect of pretreatment with 5-hydroxytryptaminergic agents. 622 27

1. In Na- and Ca-free external solutions, Sr or Ba (but not Mg) could act as carriers of inward current during action potentials in the neurone, R15 of the Aplysia abdominal ganglion. These action potentials exhibited a prolonged plateau phase, the duration of which was dependent on the concentration and species of divalent cation and activity of the neurone. 2. Depolarization of the soma membrane in Na-free Ba solution generated a prolonged, 'late' inward current the amplitude of which was dependent on the external Ba concentration. The Ba current was insensitive to tetrodotoxin but could be blocked by Mn2+ and Co2+ ions. 3. The peak current-voltage relation and threshold for activation of the late inward current was shifted to more negative potentials on replacement of Ca with Ba. The zero-current (reversal) potentials for both Sr and Ba were more negative than for Ca, indicating that the 'Ca' channel is less permeable to Sr2+ or Ba2+ ions than to Ca2+ ions. 4. Inactivation of the 'Ca' channel is slower in Ba than in Ca solution. The time course of Ba currents during a maintained depolarization of 2 sec could be reasonably described by the expression, I'Ba(t) = I'Ba (infinity) [1-exp(-t/tau M)]2exp(-t/tau H). 5. Time constants for activation (tau M) and inactivation (tau H) were voltage-dependent. In the range -10 to +30 mV, tau M varied from 15 to 5 msec and tau H from 2.0 to 0.5 sec (12 degrees C). Steady-state Ba conductance (corrected for inactivation) was voltage-dependent, increasing sigmoidally with depolarization to a maximum of approximately 12 microS at potentials beyond +15 mV. 6. Steady-state inactivation of Ba conductance (hBa(infinity)) varied with holding potential (VH). Conditioning holding potentials more negative than the resting potential (-40 to -50 mV) produced depression of Ba currents. Complete inactivation of Ba currents occurred at holding potentials more positive than 0 mV or with repetitive activation at frequencies greater than 1 Hz. 7. The divalent ions, Ba2+ and Sr2+, reversible depressed the total delayed K+ current at a rate dependent on the frequency of activation. Ba and Sr shifted the delayed K+ current-voltage curve to more positive voltages and depressed the delayed outward current at all membrane potentials. 8. Comparison of the effect of Ba on delayed K+ currents with those obtained in the presence of Mn2+ ions indicated that Ba2+ ions depress both the voltage-dependent and Ca-dependent components of the delayed K+ current. However, the mechanism by which Ba acts to inhibit the two components of the delayed K+ current appears to be different.
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PMID:Divalent ion currents and the delayed potassium conductance in an Aplysia neurone. 625 42

The effects of Mn2+, Co2+, and of Ni2+ on quantal acetylcholine (ACh) release have been studied with conventional microelectrode techniques. Increasing the [Co2+]0 or [Ni2+]0 (in the absence of extracellular Ca2+) caused an increase in miniature endplate potential (MEPP) frequency. [Mn2+]0 caused some increase in frequency at low levels, but then there was no rise as the concentration was increased further. In preparations depolarized with 20 mM K+, the MEPP frequency was a monotonically increasing function of [Co2+]0 or [Ni2+]0. In increasing concentrations of [Mn2+]0 there was an increase followed by a levelling off or a depression at higher concentrations. Tetanic stimulation of the motor nerve in solutions containing no added divalent cations or containing MgEGTA produced slight or no increases in MEPP frequency. In Mn2+-, Co2+- or Ni2+- saline solution stimulation of the motor nerve led to substantial increases in MEPP frequencies. The maximum frequency attained in Mn2+, Co2+, or Ni2+ was a power function of: (a) the duration of the tetanus; (b) the frequency of stimulation during the tetanus; or (c) the extracellular concentration of the divalent cation. During stimulation in Mn2+-saline solution the MEPP frequency reached a maximum; further stimulation led to a fall in frequency. We conclude that Mn2+, Co2+, and Ni2+ can enter the nerve terminal through a voltage-gated channel. Once within the terminal, they can stimulate quantal release by releasing Ca2+ or by causing the liberation of an activator, like H+, within the terminal.
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PMID:Tetanic stimulation increases the frequency of miniature end-plate potentials at the frog neuromuscular junction in Mn2+-, CO2+-, and Ni2+-saline solutions. 625 5

1. The depressant actions of Mg2+ and a range of other divalent ions on synaptic excitation and on responses produced by excitatory amino acids and other putative transmitters have been investigated in hemisected isolated spinal cords of frogs and neonatal rats. Some comparative studies were also made using the rat isolated superior cervical ganglion. 2. At concentrations above 10 microM, Mg2+ selectively antagonized N-methyl-D-aspartate (NMDA)-induced motoneurone depolarization as recorded from ventral roots of tetrodotoxin-blocked spinal cords. Depolarization evoked by quisqualate (unaffected by 20 mM-Mg2+) was resistant to the depressant action of these ions, while depolarizations evoked by other excitant amino acids were depressed to intermediate degrees. 3. Mn2+, Co2+ and Ni2+ had qualitatively similar actions to Mg2+; Mn2+ was somewhat less potent and Co2+ and Ni2+ more potent than Mg2+. The alkaline earth metal ions, Ca2+, Sr2+ and Ba2+, had very weak Mg2+-like actions. Ca2+ and Mg2+ acted additively in depressing amino acid-induced responses. 4. Mg2+ also depressed motoneurone responses evoked by noradrenaline, substance P and carbachol in the neonatal rat isolated spinal cord. However, none of these effects were as marked as the depression of NMDA-induced responses by Mg2+ in this preparation. Mg2+ did not depress motoneurone depolarization produced by 5-HT in the rat spinal cord or the depolarizing action of GABA on primary afferent terminals of the isolated frog spinal cord. 5. At concentrations producing marked depression of NMDA-induced responses, Mg2+ also depressed synaptic transmission in spinal cords in the absence of an effect on ganglionic transmission. At the same concentrations, Mn2+, Co2+ and Ni2+ depressed synaptic transmission in both preparations. 6. From the similarity in action between Mg2+ and the D-alpha-aminoadipate group of NMDA antagonists, it is suggested that the central depressant action of low concentrations of Mg2+ involves predominantly a postsynaptically mediated interference with the action of an excitatory amino acid transmitter.
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PMID:Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations. 625 39

Surface potentials and field potentials recorded from the medulla in response to cutaneous and mixed nerve stimulation revealed that fibers of the dorsal white column project onto two separate neuron groups in the medulla representing the dorsal column nuclei. The hind-limb was represented in the medial group and the fore-limb in the lateral group in the projection. The fore-limb nerves projected to a region extending from the medulla to the 4th segment of the spinal cord. Primary afferent depolarization and depression of synaptic activities were shown by direct and indirect stimulation of dorsal column fiber terminals in the dorsal column nuclei. Conditioning volleys set up in hind-limb nerves had no effect on test responses evoked by stimulation of forelimb nerves, and vice versa. Slow negative potentials with decreasing latencies were recorded from the posterocentral nucleus of the thalamus in response to stimulation of the 2nd dorsal root, the dorsal column and the dorsal column nuclei, respectively. The physiological results were correlated with histological observations using the cobalt labelling method. It was concluded that the amphibian dorsal column-medial lemniscus system is closely comparable with that found in the mammalian brain.
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PMID:The dorsal column nuclei of the frog. 628 44

1 Synaptic potentials and the responses of frog spinal cord to various acidic amino acids were examined by means of the sucrose gap recording technique. 2 Divalent cations (50-250 microM) specifically antagonized responses evoked at N-methyl-D-aspartate (NMDA) receptors by N-methyl D,L aspartic acid (NMDLA). The rank order of potency was Ni2+ greater than Co2+ greater than Mg2+ greater than Mn2+. Responses to glutamate and aspartate were relatively insensitive to these concentrations of divalent cations. 3 The rank order of potency for divalent ions (1 mM) for antagonism of synaptic transmission in bullfrog sympathetic ganglia was Mn2+ greater than Co2+ greater than Ni2+ greater than Mg2+. Thus synaptic transmission in ganglia was especially sensitive to Mn2+ whereas NMDLA responses were especially sensitive to Co2+ and Mg2+. 4 It was possible to depress selectively the dorsal root-dorsal root potential (DR-DRP) and dorsal root-ventral root potential (DR-VRP) of frog spinal cord using low doses of Co2+ or Mg2+ which did not affect VR-DRP (ventral root-dorsal root potential). It was not possible to produce this selective depression of DR-DRP and DR-VRP with Mn2+, as this cation non-selectively depressed all responses. 5 These results suggest that: (i) divalent cations do not antagonize NMDLA responses by blocking Ca2+ channels which may mediate the response; (ii) postsynaptic NMDA receptors are activated by a neurotransmitter involved in the DR-DRP and DR-VRP pathways but not by any neurotransmitters involved in the VR-DRP pathway; (iii) the neurotransmitter activating NMDA receptors in amphibian spinal cord may be an aspartate-like substance rather than aspartate itself or glutamate.
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PMID:The use of low concentrations of divalent cations to demonstrate a role for N-methyl-D-aspartate receptors in synaptic transmission in amphibian spinal cord. 629 90

About 80 per cent of patients with breast cancer ultimately die of metastatic disease in the following twenty years. Distant metastases are more important as cause of death than loco-regional relapses, it is why adjuvant chemotherapy is necessary, especially in young patients and in those with extensive disease. Initial chemotherapy preceding any locoregional treatment is justified on the basis that both surgery and anesthesia lead to immuno-depression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials of Nissen-Meyer, Bonadonna and Cooper. We have treated 145 patients, including 67 with inflammatory breast cancer (IBC), with 4 to 6 weeks of Velbe, Thiotepa, Methotrexate Fluorouracil and Prednisone with Adriblastine added for those patients with IBC or T greater than 7 cm, or N2 N3. Because of tumor regression of more than 50 per cent observed in 80 per cent of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium) and are in a complete remission in all these cases after curietherapy. Maintenance treatment with the same drugs was prescribed for 6 to 18 months depending on the initial staging. Tumor regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest one being 42 months. The overall survival at 2 years for IBC, is 90 per cent with a disease-free survival of 80 per cent. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.
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PMID:[Breast cancer: chemotherapy preceding locoregional treatment with extension of the indications for conservative treatment]. 643 62

The heme-cytochrome P-450 complexes represent sensitive metabolic systems for examining the biological impact of metals on important cellular functions. Many metals, both in the inorganic form and bound to organic moieties, potently induce heme oxygenase, the rate limiting enzyme of heme degradation. The resulting increase in the rate of heme breakdown is reflected in a marked depression of cellular cytochrome P-450 content and impairment of the oxidative metabolism of natural and foreign chemicals dependent on this hemeprotein. Organometal complexes do not mimic in all their aspects the actions of the inorganic elements which they contain. For example, organotins, in contrast to inorganic tin, produce a prolonged induction response of heme oxygenase in the liver but not in the kidney. Co-protoporphyrin is a much more potent inducer of heme oxygenase in liver than is inorganic cobalt; and Sn-protoporphyrin inhibits heme oxygenase activity nearly completely, whereas inorganic tin is a powerful inducer of the renal enzyme. Contrasting effects on heme metabolism exist as well within the metalloporphyrin species as demonstrated by the effects in vivo of Co-protoporphyrin and Sn-protoporphyrin on heme oxygenase activity; the former induces the enzyme whereas the latter potently inhibits it. In vitro, however, both compounds competitively inhibit heme oxidation activity. These differences, among others which characterize metal actions in vivo and in vitro attest to the importance of pharmacokinetic, adaptive and other host factors in defining the responses of the heme-cytochrome P-450 systems to the impact of metals in the whole animal.
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PMID:Control of heme and cytochrome P-450 metabolism by inorganic metals, organometals and synthetic metalloporphyrins. 654 1


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