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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary We have studied 72 families with at least one child with cystic fibrosis (CF); they were referred because they had requested pre-natal diagnosis in a future pregnancy. The ΔF508 mutation was found in 108/140 CF chromosomes (77%). In 41/72 families (57%), both parents carried a deleted chromosome and the child was doubly deleted. In only 4 families, 2 of them being consanguineous, did neither parent carry a deleted chromosome. Meconium ileus was associated with children who were ΔF508/ΔF508, ΔF508/non-deleted and non-deleted/ non-deleted.
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  • 2
    ISSN: 1432-1084
    Keywords: Diffuse liver disease ; MRI ; CT ; Ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-nine patients with diffuse liver disease were examined by ultrasound, CT and MRI. MRI was performed using T1- and T2-weighted spin-echo sequences as well as fast gradient-echo-sequences. The paramagnetic contrast agent Gd-DTPA was applied intravenously (0.1 mmol/kg). in patients with hepatitis, MRI could be used in guiding liver biopsies as inflammatory changes were clearly delineated. CT and ultrasound were superior to MRI in the detection of focal or diffuse fatty degeneration. On the other hand MRI was more helpful in differentiating fatty changes and neoplasm. In liver cirrhosis, fibrotic changes were most clearly demonstrated by MRI. In patients suffering from hemochromatosis MRI offers advantages over CT and ultrasound in the diagnosis and follow up due to the paramagnetic properties of iron, resulting in a reduction in signal intensity. In patients with Wilson's disease a characteristic pattern of parenchymal changes was seen. Administration of Gd- DTPA contributes additional information about perfusion conditions in the liver parenchyma, however this information was not of diagnostic relevance in the cases we studied.
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The N1303K mutation was identified in the second nucleotide binding fold of the cystic fibrosis (CF) gene last year. We have gathered data from laboratories throughout Europe and the United States of America in order to estimate its frequency and to attempt to characterise the clinical manifestations of this mutation. N1303K, identified on 216 of nearly 15000 CF chromosomes tested, accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele varies significantly between countries and ethnic groups, being more common in Southern than in Northern Europe. This variation is independent of the AF508 allele. It was not found on UK Asian, American Black or Australian chromosomes. N1303K is associated with four different linked marker haplotypes for the polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in the other CF allele. We classify N1303K as a “severe” mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.
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  • 4
    ISSN: 1432-1041
    Keywords: Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22–35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng·ml−1; tmax, 45 min; AUC (0–3 h), 15.1 μg·ml−1. min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were: Cmax, 228 ng·ml−1; tmax, 75 min; AUC (0–3 h), 17.0 μg·ml−1. min. tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP. tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.
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  • 5
    ISSN: 1433-8491
    Keywords: Alzheimer's disease ; Aging ; Cytoskeleton ; Glycosylation ; Neuropathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructure of Alzheimer's neurofibrillary tangles is heterogeneous and includes abnormal paired helical filaments (PHF) and various other insoluble structures. Insoluble non-PHF components isolated from neurofibrillary tangles were examined by electron microscopy. Comparison of these fractions with normal assembled neurofilaments and normal brain microtubules revealed scattered profiles which were morphologically (not chemically) identical to structures present in the microtubule, but not in the neurofilament preparations. These results support the notion that insoluble microtubules contribute to the make up of the neurofibrillary tangle. Based on these findings, preliminary experiments were conducted which suggest that non-enzymatic glycosylation may be a pathway leading to insolubility of the microtubules.
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  • 6
    ISSN: 1420-9071
    Keywords: Cardiac output ; cardio-regulatory nerves ; hemodynamics ; neurohormones ; pericardial organ ; Crustacea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This report provides the first direct measurements of the stroke volume and total cardiac output of crustacean hearts, as recorded from a semi-isolated in vitro preparation. The responses to mechanical perturbations, changes in preload and afterload, show that these hearts do not possess automatic compensatory Frank-Starling-like mechanisms. Heart rate, reflecting the burst rate of the cardiac ganglion, is minimally affected by stretch. On the other hand, these hearts are exquisitely responsive to the neurohormones of the pericardial organs. Serotonin, CCAP and proctolin all produce positive chronotropic and inotropic effects, but the responses to each are unique. Two FMRFamide peptides were positively chronotropic, but negatively inotropic.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 61 (1993), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Ba2+ has multiple effects on presynaptic terminals. The ion inhibits the K+ channels responsible for stabilizing the plasma membrane potential in the same way as previously reported for dendrotoxin and 4-aminopyridine. Secondly, the ion can substitute fully for Ca2+ in supporting KCl-evoked release of glutamate from guinea-pig cerebrocortical synaptosomes. In the latter case, the kinetics of glutamate release in the presence of saturating Ca2+ or Ba2+ are essentially identical. Substantially lower external concentrations of Ba2+ are required to achieve the same release kinetics as with Ca2+. The average internal free Ba2+ concentration attained during KCl depolarization is some 10-fold higher than that for Ca2+. However, because the fura-2 signal reflects predominantly the overflow of divalent cation after dissociation from the release trigger, it is not the valid parameter to compare effectiveness of the cations in triggering glutamate exocytosis. In view of the established inability of Ba2+ to interact with calmodulin, these results are discussed in relation to theories in which Ca2+/calmodulin-dependent protein kinase-mediated phosphorylation is a prerequisite for synaptic vesicle exocytosis.
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Regulation of catecholamine biosynthesis is crucial in the adaptation to various physiological conditions, such as stress, and in several disorders, including hypertension and depression. In this study we have found that in PC12 cells, the mRNA levels of dopamine β-hydroxylase (DBH), the enzyme that catalyzes the formation of norepinephrine from dopamine, can be regulated by glucocorticoids and cyclic AMP (cAMP) analogues. Treatment with dexamethasone increased DBH mRNA levels by 6 h, with maximal elevation (four- to fivefold) obtained after 1 day of exposure, and these levels were maintained for up to 4 days. DBH mRNA levels were also elevated on treatment of PC12 cells with 8-bromo cAMP for 8 h to 1 day. The response to 8-bromo cAMP, however, was bimodal, because DBH mRNA levels declined below control values on treatment for 〉 1 day. In combined treatments with 8-bromo cAMP and dexamethasone, the cAMP effect was dominant. To begin to characterize the regulation of DBH mRNA, genomic clones for rat DBH were isolated, and 1 kb of the 5’flanking region was sequenced. Several putative regulatory elements, which may be involved in cAMP and glucocorticoid regulation, were identified, including two adjacent cAMP response elements, another element that can also bind members of the ATF/CREB family of transcription factors, a NF-kB-like sequence, several AP-2 sites, and three core glucocorticoid receptor binding sequences.
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  • 9
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Guinea-pig cerebral cortical synaptosomes were preincubated for 60 min with 100 μMd-aspartate, l-aspartate, or l-glutamate. The total d- plus l-aspartate content of the synaptosomal fraction increased to 235%, 195%, or 164%, respectively, of the control. Despite this no increase was seen in the very low KCl evoked, Ca2+-dependent release of aspartate. Preincubation with the three amino acids changed the synaptosomal glutamate content to 78% (d-aspartate), 149% (l-aspartate), or 168% (l-glutamate) of control. However there was no statistically significant effect of these preincubations on the extent of Ca2+-dependent glutamate release. Thus the Ca2+-dependent release of aspartate and glutamate is not determined by the total synaptosomal content of these amino acids. The addition of 0.1–0.5 mM glutamine to the incubation caused a massive appearance of glutamate in the extrasynaptosomal medium. Analysis of specific activities showed that glutamine was hydrolysed directly by an extra-synaptosomal glutaminase, and that intrasynaptosomal glutamate was predominantly labelled by uptake of this glutaminase-derived glutamate. No increase was seen in the extent of Ca2+-dependent release of glutamate (by fluorimetry) either after preincubation with glutamine or in the continued presence of glutamine. Thus we are unable to confirm reports that glutamine expands the transmitter pool of glutamate. The extrasynaptosomal glutaminase activity in the synaptosomal preparation was inhibited by Ca2+ and activated by phosphate. Identical kinetics were obtained with “free'’brain mitochondria, confirming the origin of the glutamine-derived glutamate.
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  • 10
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have studied the somatotopic reorganization in dorsal horn neurons after a disruption in the normal spatial arrangement of primary sensory axons in adult rats. Muscle afferents were redirected to skin by cutting and cross-anastomosing the hindlimb gastrocnemius nerve (GN) and sural nerve (SN). It has previously been shown that after 10 – 12 weeks GN afferents innervate the hairy skin of the lateral ankle and calf (previously innervated by SN afferents) and become potentially capable of relaying information on the location and intensity of stimuli applied to the skin. We determined the receptive field and response properties of dorsal horn neurons in the lumbar spinal cord, in regions where the lower hindlimb is normally represented. In control animals (with intact or self-anastomosed sural nerves) very few neurons (〈8%) received any synaptic input from the GN as assessed by electrical stimulation of the nerve. In contrast, when this nerve innervated skin, many cells responded to GN stimulation, and these nearly all had receptive field components in the former SN territory. Moreover, in animals with cross-anastomosed nerves, cells without GN inputs all had receptive fields outside the former SN skin territory. We have shown that in all likelihood GN afferents substituted for SN afferents in subserving the low and high threshold receptive fields of dorsal horn neurons. Furthermore, for many neurons, receptive fields were formed from inappropriately regrown GN afferents and adjacent intact cutaneous afferents (in the tibial or common peroneal nerves). Therefore, when GN afferents innervate skin in adult animals, they alter their central connectivity in an appropriate manner for their new peripheral terminations, so that an orderly somatotopic representation of the hind limb skin is maintained. We suggest that this plasticity of dorsal horn somatotopy is driven in part by activity-dependent mechanisms.
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