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  • Articles  (138)
  • 1985-1989  (138)
  • 1
    ISSN: 1573-7241
    Keywords: enoximone ; heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Enoximone possesses both positive inotropic and vasodilatory properties. In heart failure, doses varying between 3 mg/kg and 6 mg/kg produce a beneficial acute hemodynamic response but have been associated with significant side effects. Little is known about the long-term hemodynamic efficacy of this agent. To assess whether a lower dose of enoximone could produce both acute and long-term hemodynamic benefits and be better tolerated, 15 patients with refractory heart failure were given enoximone 100 mg every 8 hours (mean dose, 1.7 mg/kg). The cardiac index, pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, systemic vascular resistance, pulmonary vascular resistance, and stroke volume index all improved significantly during the first 24 hours. The systemic blood pressure and heart rate did not alter appreciably during this period. Five of six patients remaining on therapy at 6 months had a follow-up hemodynamic study. Sustained improvement was seen in the cardiac index, pulmonary capillary wedge pressure, and pulmonary artery pressure when compared to baseline (all p〈0.05). A satisfactory trend, which did not reach statistical significance, was noted in the right atrial pressure (p=0.09) and stroke volume index (p=0.06). Diarrhea occurred in one patient. These findings indicate that enoximone has a beneficial acute and long-term hemodynamic effect at a low dose that is clinically well tolerated.
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  • 2
    ISSN: 1573-904X
    Keywords: (±)l-iodo-MK-801 ; radiosynthesis ; autoradiogram ; receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The glutamate analogue N-methyl-D-aspartate (NMDA) binds to a subset of glutamate receptors that are coupled to a voltage-sensitive cation channel. This NMDA-linked channel is the likely binding locus of the potent anticonvulsant MK-801. To develop single-photon emission computed tomography (SPECT) probes of this brain channel, we synthesized (±)l-iodo-MK-801 and (±)l-[125I]iodo-MK-801. The effect of (±)l-iodo-MK-801 on ligand binding to the NMDA-linked glutamate receptor site was assessed using a rat brain homogenate assay. (±)l-Iodo-MK-801 displaced the dissociative anesthetic ligand [3H]N-[l-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding with an IC50 of 1 µM, which is a 10-fold lower binding affinity than that of (±)MK-801. In in vivo autoradiographic studies, (±)MK-801 failed to block selective uptake of (±)l-iodo-MK-801 in rat brain. These results suggest that (±)l-iodo-MK-801 may not be a suitable ligand for mapping NMDA-linked glutamate receptor channels.
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  • 3
    ISSN: 0749-1581
    Keywords: ESR ; Cation migration ; Line-width variation ; 2-Pivaloyl-1,4-benzoquinone ; Radical anion ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 2-pivaloyl-1,4-benzoquinone radical anion has been prepared by alkali metal reduction in tetrahydrofuran in the presence of dibenzo-18-crown-6, 15-crown-5, or 12-crown-4, and its ESR spectrum in each system has been recorded over a range of temperatures. Line-width variation in the ESR spectrum is observed in some systems. This line-width variation has been attributed to cation migration between sites adjacent to the non-equivalent carbonyl groups rather than to restricted rotation of the pivaloyl group. In some systems, however, the rate of migration is too fast and in others too slow, compared with the time-scale of the ESR experiment, for line-width variation to be observed. The influence of each crown ether upon the rate of cation migration has been found to depend upon the size of the crown ether ‘cavity’ compared with the size of the alkali metal counter-ion.
    Additional Material: 1 Ill.
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  • 4
    ISSN: 1573-4919
    Keywords: calmodulin ; protein kinase ; sarcolemma ; phosphorylation ; substrate proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Sarcolemmal vesicles prepared from rabbit heart muscle by differential and discontinuous sucrose density gradient centrifugation, exhibited high marker enzyme activities: Na+ + K+ ATPase 22 µMol Pi × mg−1 × h−1. Adenylate cyclase 500 pmole CAMP × mg−1 × min−1, calcium antagonist receptors 0.7 pmoles × mg−1. Calmodulin in the presence of calcium and γ-ATP32 stimulated rapidly and specifically the 32P incorporation into two membrane proteins of 54 and 44 kDa. Calmodulin stimulated the phosphorylation of the 44 kDa to a greater extent (17.9 pmol 32P × mg−1 protein) than the 54 kDa protein (1.3 pmoles 32P x mg−1 protein). Removal of endogenous calmodulin from the membrane by EGTA extraction resulted in a 2.5 fold increase in calmodulin dependent 32P incorporation into the two proteins in the presence of exogenous calmodulin. It is suggested that the calmodulin dependent protein kinase activity in heart sarcolemma may mediate the effects of calmodulin in the regulation of Ca2+ transport across the membrane.
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  • 5
    ISSN: 1573-2568
    Keywords: Barrett ; esophagus ; reflux ; gastrin ; acid ; cimetidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gastric acid secretion in response to a protein meal and to exogenously administered synthetic human gastrin 17-I was measured in patients with Barrett's esophagus, patients with uncomplicated gastroesophageal reflux, and normal age- and sex-matched controls. Acid secretion, both basally and in response to gastrin 17-I, was significantly greater in patients with Barrett's esophagus compared to normal individuals without reflux. Basal gastrin levels and meal-stimulated levels of the hormone were similar among all three groups. Sensitivity to gastrin, expressed as the concentration causing half-maximal acid secretion, was also similar among the study groups. It is speculated that elevated basal acid production in Barrett's esophagus may contribute to the pathogenesis of the disorder.
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  • 6
    ISSN: 1573-5117
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 7
    ISSN: 1573-4919
    Keywords: calcium antagonists ; purification ; receptors ; protein kinase ; phosphorylation ; subunits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Tritiated analogues of the Ca2+ channel blockers such as [3H] PN200-110, [3H] verapamil and [3H] diltiazem have been used to identify and isolate Ca2+ antagonist receptors. The Ca2+ antagonist binding sites were solubilized from skeletal muscle transverse tubules with the detergent CHAPS and purified by wheat germ lectin column chromatography and sucrose density gradient centrifugation. The isolated proteins retained their ability to bind the various classes of Ca2+ channel blockers. Polypeptides of 170, 150, 108, 56, and 32 kDa were found to be present in the purified receptor fraction when analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis under non-reducing conditions. The apparent molecular weight of the 170 kDa polypeptide changed to 145 kDa in the presence of reducing agents, as where the apparent molecular weight of the 150, 108, 56 and 32 kDa peptides remained unchanged. An endogenous protein-kinase present in the original membranes, co-purified with the receptor and stimulated the phosphorylation of the 150 and 56 kDa polypeptides in the isolated fraction.
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  • 8
    ISSN: 1573-4919
    Keywords: calcium antagonists ; receptors ; heart sarcolemma ; purification ; phosphorylation ; glycoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The Ca2+ antagonist binding sites associated with the voltage dependent calcium channel in rabbit myocardium were found to distribute with the sarcolemmal Na− + K+ ATPase and adenylate cyclase activities during subcellular fractionation on sucrose-density gradients. The equilibrium dissociation constants (KD) for the binding of [3H]nitrendipine and [3H]verapamil were 0.31 ± 0.04 nM and 4.1 ± 0.5 nM respectively, and displayed an average density of 0.55 ± 0.05 pmol/mg and 0.4 ± 0.03 pmol/mg protein respectively for the most enriched membrane fraction. The Ca2+2 antagonist binding sites were solubilized from the membranes with the detergent 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate, and specific binding sites for [3H]PN200-110, [3H]verapamil and [3H]diltiazem were isolated on a wheat-germ lectin column. The binding sites for [3H]PN200-110 were enriched about 2500 fold as compared with the original homogenate and displayed a density of 28.5 ± 8 pmole/mg protein in the isolated fraction. Sodium dodecyl sulfate gel electrophoresis of the isolated drug binding proteins indicated enrichment of proteins of Mr 170000, 140000, 130000, 100 000 and 53000. The isolated receptor contained an intrinsic kinase activity that phosphorylated glycoproteins of Mr 170 000 and 53000. Exogenously added cAMP-kinase stimulated phosphorylation of the 170000, 100000, 53 000 and 28000 Mr glycoproteins in the receptor fraction. The results of this study indicate that the binding sites for [3H]nitrendipine, [3H]PN200-110, [3H]verapamil and [3H]diltiazem residue on glycoprotein(s) which are of sarcolemmal origin, and co-purify together on wheat germ lectin columns. The polypeptide composition of the Ca2+ antagonist binding sites from cardiac muscle appears to be very similar to that of the dihydropyridine receptor in skeletal muscle.
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  • 9
    ISSN: 1573-5117
    Keywords: community dynamics ; eutrophication ; macrophyte decline ; periphyton ; phytoplankton
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Shoe Lake and East Graham Lake, part of a small chain of lakes in southeastern Michigan, USA, differ in nutrient loading and in the structure and productivity of their aquatic plant communities. A comparative study of species frequency and biomass distributions, nutrient contents, and responses to experimental nutrient enrichment and shading, was conducted to determine the principal factors controlling the macrophyte dynamics. A central objective was to address the question of why rooted macrophyte growth declines with eutrophication, and to test existing models designed to explain this phenomenon. In the more eutrophic Shoe Lake, diversity and productivity of rooted macrophytes were relatively low, restricted primarily by combined shading of phytoplankton, periphyton, and non-rooted macrophytes (principally Ceratophyllum demersum, along with Utricularia vulgaris and Cladophora fracta). In the less eutrophic East Graham Lake, lower nitrogen availability restricted the growth of all of these shading components, resulting in clearer water and higher productivity and diversity of rooted macrophytes. The macrophytes did not allelopathically suppress the phytoplankton in East Graham Lake. The results supported a direct relationship between nutrient loading, increasing growth of phytoplankton, periphyton and non-rooted macrophytes, and decline of rooted macrophytes.
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  • 10
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The potential for transcytosis (endocytosis → intracellular transport → exocytosis) of protein and membrane events associated with fluid phase and adsorptive endocytic processes within epithelia of the choroid plexus [blood-cerebrospinal fluid (CSF) barrier] were investigated in mice injected intravenously or into the lateral cerebral ventricle with native horseradish peroxidase (HRP) or the lectin wheatgerm agglutinin (WGA) conjugated to HRP. WGA binds to specific cell surface oligosaccharides and enters cells by the process of adsorptive endocytosis; native HRP is taken into cells non-specifically by fluid phase endocytosis. The lysosomal system of organelles and the endoplasmic reticulum, identified by enzyme cytochemical markers applied to choroid epithelia, were analysed for possible participation in transcytosis and compared to epithelial organelles harbouring the exogenous tracer proteins. Blood-borne native HRP was endocytosed readily by choroid epithelia whereas WGA-HRP was not, perhaps because WGA-HRP does not escape fenestrated endothelia as easily as native HRP. The blood-borne proteins incorporated within endocytic vesicles by choroid epithelia were directed to endosomes (prelysosomes) and secondary lysosomes (e.g. tubules, multivesicular/dense bodies) for eventual degradation and did not reach the apical/microvillus surface. Both CSF-borne native HRP and WGA-HRP entered choroid epithelia within endocytic vesicles derived from the microvillus border. Native HRP, ultimately sequestered within endosomes and secondary lysosomes, failed to undergo transcytosis through the epithelia into the basolateral clefts. Conversely, CSF-borne WGA-HRP was transported through the epithelia and released into the basolateral clefts within 10 min post-injection. The lectin conjugate labelled epithelial vesicles, endosomes, secondary lysosomes and, at 30 min post-injection, the transmost saccule of the Golgi complex which exhibits acid hydrolase activity. Tubular profiles, related either to the endosome apparatus or to the lysosomal system, and the endoplasmic reticulum did not appear involved in the transcytotic pathway. The data suggest that CSF-borne protein entering the choroid epithelium by adsorptive endocytosis can undergo rapid transcytosis through the cell. The results provide insight to transcytotic pathways utilizing vesicles, the endosomal apparatus, and the Golgi complex within the choroid epithelium for circumventing the blood-CSF barrier. Hypothesized membrane events and morphological associations among constituents of the endomembrane system within the choroid epithelium are summarized diagrammatically.
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