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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 35 (1992), S. 472-485 
    ISSN: 1432-1432
    Keywords: LINE-1 (L1) ; Peromyscus ; Repetitive elements ; Molecular drive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Two distinct members of the LINE-1 (L1) family in Peromyscus were characterized. The two clones, denoted L1Pm55 and L1Pm62, were 1.5 kb and 1.8 kb in length, respectively, and align to the identical region of the L1 sequence of Mus domesticus. Sequence similarity was on the order of 70% between L1Pm55 and L1Pm62, which approximates that between either Peromyscus sequence and Mus Ll. L1Pm62 represents a more prevalent subfamily than L1Pm55. L1Pm62 exists in about 500 copies per haploid genome, while L1Pm55 exists in about 100 copies. The existence of major and minor subpopulations of L1 within Peromyscus is in contrast to murine rodents and higher primates, where L1 copy number is on the order of 20,000 to 100,000, and where levels of intraspecific divergence among L1 elements are typically less than 15–20%. Additional Peromyscus clones are similarly divergent from both L1Pm62 and LIPm55, implying the existence of more than two distinct L1 subfamilies. The highly divergent L1 subfamilies in Peromyscus apparently have been evolving independently for more than 25 million years, preceding the divergence of cricetine and murine rodents. Investigations of the evolution of L1 within Peromyscus by restriction and Southern analysis was performed using species groups represented by the partially interfertile species pairs P. maniculatus-P. polionotus, P. leucopus-P. gossypinus, and P. truei-P. difficilis of the nominate subgenus and P. californicus of the Haplomylomys subgenus. Changes in L1 and species group taxonomic boundaries frequently coincided. The implications for phylogeny are discussed.
    Type of Medium: Electronic Resource
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  • 2
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    Unknown
    Woodstock, Md., etc : Periodicals Archive Online (PAO)
    Theological Studies. 52:4 (1991:Dec.) 775 
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  • 3
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The histamine-receptor subtype mediated effects on action potentials of electrically driven and spontaneously active isolated sheep cardiac Purkinje fibres were investigated using H1-and H2-selective agonists and antagonists. In electrically stimulated Purkinje fibres histamine (3 μmol/l) increased action potential plateau height, decreased action potential duration at −60mV, and enhanced pacemaker activity. These effects were abolished by 30 μmol/l cimetidine (H2-selective antagonist), but not impaired by 0.3 μmol/l dimethindene (H1-selective antagonist). In spontaneously active Purkinje fibres, histamine (10 μmol/l) increased the spontaneous rate by 24%, the slope of diastolic depolarization by 45% and shortened the duration of the diastole at −60mV by 32% of the respective control measurements. These effects were blocked by 30 μmol/l cimetidine, but not by 0.3 μmol/l dimethindene. The concentration-response relationship of histamine was shifted to higher histamine concentrations by approximately 2 logarithmic units in the presence of 30 μmol/l cimetidine, but no displacement was found in the presence of 0.3 μmol/l dimetindene. The H2-selective agonist impromidine (0.001–0.3 μmol/l) has similar actions to histamine on spontaneously active Purkinje fibres, while the H1-selective agonist 2-(2-pyridyl-)ethylamine was ineffective. It is concluded that the pronounced stimulatory action of histamine on spontaneous activity in sheep cardiac Purkinje fibres is exclusively mediated by H2-receptors.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The histamine-receptor-subtype-mediated effects on action potentials of electrically driven and spontaneously active isolated sheep cardiac Purkinje fibers were investigated using H1-and H2-selective agonists and antagonists. In electrically stimulated Purkinje fibers, histamine (3 μmol/l) increased the action potential plateau height, decreased the action potential duration measured at a repolarization level of −60 mV and enhanced the pacemaker activity. These effects were abolished by the H2-selective antagonist cimetidine (30 μmol/l), but were not impaired by the H1-selective antagonist dimetindene (0.3 μmol/l). In spontaneously active Purkinje fibers, histamine (10 μmol/l) increased the spontaneous rate by 24%, the slope of diastolic depolarization by 45% and shortened the duration of the diastole by 32% of the respective control measurements. These effects were blocked by 30 μmol/l cimetidine, but remained unchanged in the presence of 0.3 μmol/l dimetindene. Concentration-response curves of histamine were shifted to the right by approximately 2 logarithmic units in the presence of 30 μmol/l cimetidine, but were not influenced in the presence of 0.3 μmol/l dimetindene. The H2-selective agonist impromidine (0.001–0.3 μmol/l) had similar actions as histamine on spontaneously active Purkinje fibers, while the H1-selective agonist 2-(2-pyridyl-)ethylamine was ineffective. It is concluded that the pronounced stimulatory action of histamine on spontaneous activity in sheep cardiac Purkinje fibers is exclusively mediated by H2 receptors.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 594-601 
    ISSN: 1432-1912
    Keywords: Key words: Macrophage – Voltage-clamp – Potassium current – Zymosan – Platelet activating factor – Calcium ionophore A 23187
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The effects of zymosan and human serum opsonized zymosan on membrane currents of adherent mouse peritoneal macrophages which had been cultured for 5 to 20 days were investigated with the whole-cell voltage-clamp technique. Both stimuli activated an outward current. The outward current activation was transient and lasted about 5 min. In solutions with 10 or 50 mmol/l extracellular potassium concentration the activation of an outwardly directed current occurred at test potentials positive to the respective potassium equilibrium potential. This particle-induced current resembled a calcium-activated potassium current which could be activated with the calcium ionophore A 23187 and with platelet activating factor. The order of maximal responses (test potential +55 mV, amplitude given as percentage of the respective control) was: 0.1 μmol/l platelet activating factor (222±36%, n=8, P〈0.01) 〈1 μmol/l A 23187 (190±24%, n=11, P〈0.01) 〈900 μg/ml opsonized zymosan (134±7%, n=22, P〈0.01) 〈900 μg/ml zymosan (116±5%, n=21, P〈0.01). The lower efficiency of zymosan as compared to opsonized zymosan is explained in part by a lower percentage of responding cells which was 48% for zymosan and 73% for opsonized zymosan. Macrophages which were pretreated with particles showed a greater reactivity to calcium as compared to untreated cells. Elevation of extracellular calcium from 0.9 to 4.5 mmol/l activated the outward current to 145±12% (n=11, P〈 0.01) after preincubation with opsonized zymosan and to 144±21% (n=12, P〈0.01) under the influence of zymosan while in untreated cells current increase by elevation of extracellular calcium was not significant (120±10%, n=9, n.s.).
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 207-212 
    ISSN: 1432-1912
    Keywords: Macrophage ; Voltage-clamp ; Ionic current ; Low density lipoprotein ; Acetylated low density lipoprotein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to search for electrophysiological effects of human lipoproteins on membrane currents in mouse peritoneal macrophages which had been cultured for 5 to 20 days. Whole-cell currents were recorded by using a voltage-clamp technique. Low density lipoprotein (LDL, 100 μg/ml) increased a slowly activating nonspecific cation current (iso) in the positive potential range to 244 ± 23% of the reference (test potential + 55 mV, n = 13, P 〈 0.005). Augmentation of current resulted out of a negative shift of the activation curve along the voltage axis (−22 mV) and an increase of maximally available current. Furthermore, LDL increased a rapidly activating outward current (ifo) at test potentials positive to the potassium equilibrium potential. At +55 mV ifo-amplitude increasedto 165 ± 14% ofreference (n = 16, P 〈 0.005). LDL-induced effects on ifo-current could be mimicked by application of the calcium ionophore A 23187 (1 μmol/l) which led to an increase of ifo-current to 161 ± 25% of the reference (test potential + 55 mV, n = 11, P 〈 0.005). Acetylated-LDL (100 μg/ml, 5–15 min) produced no significant effect on the membrane currents under investigation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 594-601 
    ISSN: 1432-1912
    Keywords: Macrophage ; Voltage-clamp ; Potassium current ; Zymosan ; Platelet activating factor ; Calcium ionophore A 23187
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of zymosan and human serum opsonized zymosan on membrane currents of adherent mouse peritoneal macrophages which had been cultured for 5 to 20 days were investigated with the whole-cell voltage-clamp technique. Both stimuli activated an outward current. The outward current activation was transient and lasted about 5 min. In solutions with 10 or 50 mmol/l extracellular potassium concentration the activation of an outwardly directed current occurred at test potentials positive to the respective potassium equilibrium potential. This particle-induced current resembled a calciu-mactivated potassium current which could be activated with the calcium ionophore A 23187 and with platelet activating factor. The order of maximal responses (test potential +55 mV, amplitude given as percentage of the respective control) was: 0.1 μmol/l platelet activating factor (222±36%,n=8,P〈0.01) 〉 1 μmol/l A 23187 (190±24%,n=11,P〈0.01) 〉900 μg/ml opsonized zymosan (134±7%,n=22,P〈0.01) 〉900 μg/ml zymosan (116±5%,n = 21,P〈0.01) The lower efficiency of zymosan as compared to opsonized zymosan is explained in part by a lower percentage of responding cells which was 48% for zymosan and 73% for opsonized zymosan. Macrophages which were pretreated with particles showed a greater reactivity to calcium as compared to untreated cells. Elevation of extracellular calcium from 0.9 to 4.5 mmol/l activated the outward current to 145±12% (n = 11,P〈 0.01) after preincubation with opsonized zymosan and to 144±21% (n = 12,P〈 0.01) under the influence of zymosan while in untreated cells current increase by elevation of extracellular calcium was not significant (120±10%,n = 9, n.s.).
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 677-684 
    ISSN: 1432-1912
    Keywords: Key words: Sheep cardiac Purkinje fibre – Pacemaker current – Action potential – Bradycardic agent – ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The bradycardic mechanism of ZD 7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)py-rimidinium chloride) was investigated in sheep cardiac Purkinje fibres. The pacemaker if-current measured with the two-microelectrode voltage-clamp technique, as well as the diastolic depolarization rate and the frequency of spontaneously active fibres were evaluated.   ZD 7288 did inhibit if-current. The if-amplitude recorded with a 0.8s-lasting test pulse from about –50 mV to –100 mV was reduced to 50% of control at 0.85 μmol/l and to 5% of control at 10 μmol/l. The threshold potential of if-activation was unaffected at a concentration of 1 μmol/l ZD 7288. The time constant of if-activation at different test potentials was not changed by 1 μmol/l ZD 7288. The drug was equally effective during if-activation with a 0.5 s-lasting test pulse applied at 0.05 Hz or 0.5 Hz. During long lasting (5 s) hyperpolarizing test pulses (–120 mV) the inhibition of if-current was removed.   In constantly stimulated Purkinje fibres (0.5 Hz) the slope of the early diastolic depolarization was decreased by ZD 7288. The half-maximal effect occurred at 0.92 μmol/l. There was strong correlation over the concentration range of 0.01 to 10 μmol/l ZD 7288 between the decrease of the slope of early diastolic depolarization and inhibition of if-amplitude recorded with 0.8s-lasting test pulses to –100 mV. The correlation coefficient was r=0.97.   These results will explain the decrease in frequency of spontaneously active (about 0.6 Hz) Purkinje fibres. At 0.3 μmol/l ZD 7288 spontaneous activity had stopped in 8 of 11 preparations. Complete recovery of drug-induced effects on the frequency was gained after 3 h of wash-out with drug-free solution.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1912
    Keywords: Sheep Purkinje fibre ; Action potential ; Potassium outward currents ; Pacemaker current ; YS 035
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The electrophysiologic mode of action and potency of the verapamil derivative YS 035 (N,N-bis-(3,4-dimethoxyphenethyl)-N-methyl amine) were investigated in sheep cardiac Purkinje fibres. Action potential duration measured at a repolarization level of −60 mV (APD-60) and membrane currents recorded with the two-microelectrode voltage-clamp technique were evaluated. At 10 μmol/l YS 035 APD-60 was increased to about 115% of reference. Prolongation measured as percentage of the respective control exhibited on the average no dependence on stimulation frequency (0.17–2 Hz). At 100 μmol/l membrane became depolarized to about −50 mV and action potentials could no longer be elicited. Further study was focussed on effects on outward currents, mostly activated at a frequency of 0.05 Hz. Transient outward current (ito) was completely blocked at 100 μmol/l and half-maximal inhibition occurred at about 14 μmol/l. Inwardly rectifying potassium current (iK1) was reduced to 47% of reference at 100 μmol/l. An initially activating outward current at positive membrane potentials (iinst) was reduced to 73% at 100 μmol/l. Time-dependent (delayed) outward current (iK) was on the average not affected up to 100 μol/l. Besides inhibition of repolarizing outward currents YS 035 completely blocked pacemaker current (if) at 100 μmol/l and half-maximal reduction was achieved at 5 μmol/l. YS 035 (1–100 μmol/l) did not clearly affect time constants of activation at selected test potentials (IK: +35 mV; if: −90 mV) or inactivation (ito: 0 mV). Voltage-dependent control mechanisms of currents (itto, if) were not influenced by YS 035 but the amount of available current was reduced. In conclusion, the verapamil derivative YS 035 inhibited pacemaker current and potassium outward currents which correlated to a prolongation of cardiac action po tentials. Electrophysiological actions of the compound favour it to be tested in vivo as an antiarrhythmic drug candidate.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 677-684 
    ISSN: 1432-1912
    Keywords: Sheep cardiac Purkinje fibre ; Pacemaker current ; Action potential ; Bradycardic agent ; ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The bradycardic mechanism of ZD 7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride) was investigated in sheep cardiac Purkinje fibres. The pacemaker if-current measured with the two-microelectrode voltage-clamp technique, as well as the diastolic depolarization rate and the frequency of spontaneously active fibres were evaluated. ZD 7288 did inhibit if-current. The if-amplitude recorded with a 0.8s-lasting test pulse from about −50 mV to −100 mV was reduced to 50% of control at 0.85 μmol/l and to 5% of control at 10 μmol/l. The threshold potential of if-activation was unaffected at a concentration of 1 μmol/l ZD 7288. The time constant of if-activation at different test potentials was not changed by 1 μmol/l ZD 7288. The drug was equally effective during if-activation with a 0.5 s-lasting test pulse applied at 0.05 Hz or 0.5 Hz. During long lasting (5 s) hyperpolarizing test pulses (−120 mV) the inhibition of if-current was removed. In constantly stimulated Purkinje fibres (0.5 Hz) the slope of the early diastolic depolarization was decreased by ZD 7288. The half-maximal effect occurred at 0.92 μmol/l. There was strong correlation over the concentration range of 0.01 to 10 μmol/l ZD 7288 between the decrease of the slope of early diastolic depolarization and inhibition of if-amplitude recorded with 0.8s-lasting test pulses to −100 mV. The correlation coefficient was r = 0.97. These results will explain the decrease in frequency of spontaneously active (about 0.6 Hz) Purkinje fibres. At 0.3 μmol/l ZD 7288 spontaneous activity had stopped in 8 of 11 preparations. Complete recovery of drug-induced effects on the frequency was gained after 3 h of wash-out with drug-free solution.
    Type of Medium: Electronic Resource
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