ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • pharmacokinetics  (2,025)
  • Rat  (826)
  • Drosophila  (737)
  • Inversion
  • Springer  (3,622)
  • American Geophysical Union  (2)
  • Institut für Meteorologie und Geophysik  (2)
  • Wiley  (2)
  • 3
  • 1
    Publication Date: 2022-05-25
    Description: Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 38 (2011): L09804, doi:10.1029/2011GL047238.
    Description: Atmospheric mixing ratios of CO2 are strongly seasonal in the Arctic due to mid-latitude transport. Here we analyze the seasonal influence of moist synoptic storms by diagnosing CO2 transport from a global model on moist isentropes (to represent parcel trajectories through stormtracks) and parsing transport into eddy and mean components. During winter when northern plants respire, warm moist air, high in CO2, is swept poleward into the polar vortex, while cold dry air, low in CO2, that had been transported into the polar vortex earlier in the year is swept equatorward. Eddies reduce seasonality in mid-latitudes by ∼50% of NEE (∼100% of fossil fuel) while amplifying seasonality at high latitudes. Transport along stormtracks is correlated with rising, moist, cloudy air, which systematically hides this CO2 transport from satellites. We recommend that (1) regional inversions carefully account for meridional transport and (2) inversion models represent moist and frontal processes with high fidelity.
    Description: This research is supported by the National Aeronautics and Space Administration contracts NNX08AT77G, NNX06AC75G, and NNX08AM56G.
    Keywords: Atmospheric transport ; Carbon cycle ; Inversion ; Isentropic coordinates ; Synoptic weather ; Tracer modeling
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: application/pdf
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2022-05-26
    Description: Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 25 (2010): PA4222, doi:10.1029/2010PA001936.
    Description: Observations and an ocean box model are combined in order to test the adequacy of the freshwater forcing hypothesis to explain abrupt climate change given the uncertainties in the parameterization of vertical buoyancy transport in the ocean. The combination is carried out using Bayesian stochastic inversion, which allows us to infer changes in the mass balance of Northern Hemisphere (NH) ice sheets and in the meridional transports of mass and heat in the Atlantic Ocean that would be required to explain Dansgaard-Oeschger Interstadials (DOIs) from 30 to 39 kyr B.P. The mean sea level changes implied by changes in NH ice sheet mass balance agree in amplitude and timing with reconstructions from the geologic record, which gives some support to the freshwater forcing hypothesis. The inversion suggests that the duration of the DOIs should be directly related to the growth of land ice. Our results are unaffected by uncertainties in the representation of vertical buoyancy transport in the ocean. However, the solutions are sensitive to assumptions about physical processes at polar latitudes.
    Description: This material is based upon work supported by the National Science Foundation under grant OCE‐0402363 and Department of Energy grant DE‐FG02‐08ER64619.
    Keywords: Inversion ; MOC ; Abrupt ; Sea level ; Coral ; Mixing
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Format: application/postscript
    Format: application/pdf
    Format: text/plain
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2017-04-04
    Description: We show the magnetic model of the Selli-Vavilov region. The Selli Line is known as the northwestern edge of the southern Tyrrhenian basin. The tectonic evolution of the Tyrrhenian basin is dominated by a Tortonian - Quaternary extension through the eastward movement of the Apennine subduction system. This migration has generated a diffuse stretching of the continental crust with the emplacement of new oceanic material. This latter occurred in several localized zones where the eastward retreating of the Ionian subduction system produced a strong depletion of the crust with formation of basins and correlated spreading. Nowadays the presence of oceanic crust is confirmed through direct drilling investigation but a complete mapping of the oceanic crustal distribution is still lacking. The Selli-Vavilov region shows a differentiated crustal setting where seamount structures, the oceanic basement portions and continental crust blocks are superimposed. To this aim, a 2D inversion of the magnetic data of this region was conducted to define buried structures. The magnetic susceptibility pattern was computed by solving the least squares problem of the misfit between the predicted and real data for separated wavebands. This method produced two 2D models of the high and low frequency fields of the Selli-Vavilov region. The two apparent susceptibility maps provide different information for distinct ranges of depth. The results of the inversions were also combined with seismic data of the Selli region highlighting the position of the highly-magnetized buried bodies. The results confirm a role for the Selli Line as a deep crustal boundary dividing the Sardinian passive domain from the easternmost active region where different oceanic structures are located. The Selli Line has worked as a detachment fault system which has moved eastward. Finally, the Selli-Vavilov region may be interpreted as a tectonic result due to a passive asymmetrical rift occurred between the Tortonian and Pliocene.
    Description: Published
    Description: 251-266
    Description: 2.6. TTC - Laboratorio di gravimetria, magnetismo ed elettromagnetismo in aree attive
    Description: 3.4. Geomagnetismo
    Description: 3.5. Geologia e storia dei sistemi vulcanici
    Description: JCR Journal
    Description: reserved
    Keywords: Geomagnetism ; Tectonics ; Geodynamics ; Inversion ; Oceanic crust ; Volcanic structure ; 04. Solid Earth::04.05. Geomagnetism::04.05.04. Magnetic anomalies ; 04. Solid Earth::04.07. Tectonophysics::04.07.02. Geodynamics ; 05. General::05.01. Computational geophysics::05.01.03. Inverse methods
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 4
    facet.materialart.
    Unknown
    3
    In:  Computers and Geosciences, Münster, 3, vol. 28, no. 45, pp. 309-326, pp. L11609, (ISBN 0-471-26610-8)
    Publication Date: 2002
    Keywords: Inversion ; Data analysis / ~ processing ; Non-linear effects ; Discrimination ; C&G
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 5
    facet.materialart.
    Unknown
    Springer
    In:  Berlin, 306 pp., Springer, vol. 2, no. XVI:, pp. 1-14, (ISBN: 0-387-30752-4)
    Publication Date: 2000
    Keywords: Textbook of geophysics ; Textbook of geology ; Textbook of mathematics ; Data analysis / ~ processing ; Modelling ; Inversion
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 6
    facet.materialart.
    Unknown
    Springer
    In:  New York, Springer, vol. 31, no. 3, pp. 2-203, (ISBN 0-87590-533-1)
    Publication Date: 2000
    Keywords: Data analysis / ~ processing ; Error analysis ; Handbook of geophysics ; Handbook of geodesy ; toolbox ; Statistical investigations ; Inversion ; Non-linear effects ; aerial ; images ; Diffraction ; Tomography ; 1214 ; Geodesy ; and ; gravity ; Geopotential ; theory ; and ; determination ; 1224 ; Photogrammetry ; remote ; sensing ; 0902 ; Exploration ; geophysics ; Computational ; methods, ; seismic ; Gruen ; Grun
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 94 (2000), S. 159-171 
    ISSN: 1570-7458
    Keywords: Drosophila ; induction ; habituation ; associative learning ; T-maze olfactometer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Experiments reported in this paper investigate the properties of a change in the responsiveness of adult Drosophila melanogaster induced by exposure to different rearing media. This effect has previously been described as habituation or associative learning. Exposure to food medium containing 0.08% menthol induced a positive response to menthol odour in a T-maze olfactometer. A brief (one hour) exposure to mentholic food just before testing was sufficient to induce a change in responsiveness. The effect did not persist through periods of more than an hour of separation from mentholic medium. Effects induced by exposure to a single compound were not specific to that compound alone. Menthol-reared flies (MRFs) differed from plain reared flies (PRFs) in their responsiveness to the odours of benzaldehyde and ethyl acetate, as well as menthol, and exposure to ethyl acetate induced a change in response to menthol odour. That there was an induced positive response to menthol in MRFs suggests that conventional habituation is insufficient to explain the induced change in responsiveness, but the generalised nature of this behavioural induction in MRFs is hard to explain in terms of associative learning. The mechanism underlying the induction remains elusive.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1572-8889
    Keywords: courtship song ; wingbeat ; sexual isolation ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1572-8889
    Keywords: Drosophila ; copulatory courtship ; mate choice ; cryptic female choice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Two endemic Australian Drosophila species, D. birchii and D. serrata, have a copulatory courtship, i.e., the males court the female mainly during copulation. In the present study we found the males of both species to mount their prospective mating partners selectively, exhibiting both sex and species recognition. The males began to sing after mounting the female, and they often exhibited also postcopulatory displays typical to copulatory courtship. D. birchii and D. serrata females discriminated against males which did not sing during mounting/copulation, which suggests that the females utilize cryptic female choice. Our findings raise the question of how widespread a phenomenon cryptic female choice is in Drosophila species.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Geometriae dedicata 83 (2000), S. 31-37 
    ISSN: 1572-9168
    Keywords: Vollständiges Viereck ; Kegelschnittbüschel ; Konjugiertheitsabbildung ; Inversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract The conjugacy mapping rel. to a complete quadrangle in a Pappian projective plane of characteristic ≠2 is constructed by using a bijection of the line set onto the bundle of conics through the diagonal points of the quadrangle. The inversion with center O of the inversion circle going through the point P in the Euclidean plane proves to be the product of the reflection at OP and the affine restriction of the conjugacy mapping rel. to the quadrangle having P as one of its vertices and O together with the circular points at infinity as diagonal points.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 11
    ISSN: 1432-041X
    Keywords: Key words Brain development ; Axonal scaffold ; Extradenticle ; Homothorax ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  During early brain development in Drosophila a highly stereotyped pattern of axonal scaffolds evolves by precise pioneering and selective fasciculation of neural fibers in the newly formed brain neuromeres. Using an axonal marker, Fasciclin II, we show that the activities of the extradenticle (exd) and homothorax (hth) genes are essential to this axonal patterning in the embryonic brain. Both genes are expressed in the developing brain neurons, including many of the tract founder cluster cells. Consistent with their expression profiles, mutations of exd and hth strongly perturb the primary axonal scaffolds. Furthermore, we show that mutations of exd and hth result in profound patterning defects of the developing brain at the molecular level including stimulation of the orthodenticle gene and suppression of the empty spiracles and cervical homeotic genes. In addition, expression of a Drosophila Pax6 gene, eyeless, is significantly suppressed in the mutants except for the most anterior region. These results reveal that, in addition to their homeotic regulatory functions in trunk development, exd and hth have important roles in patterning the developing brain through coordinately regulating various nuclear regulatory genes, and imply molecular commonalities between the developmental mechanisms of the brain and trunk segments, which were conventionally considered to be largely independent.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Environmental geology 39 (2000), S. 360-371 
    ISSN: 1432-0495
    Keywords: Key words Environmental geophysics ; Resistivity ; Inversion ; Landfill mining ; Waste ; Characterization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract  Geophysical investigations using 2-D DC resistivity were carried out on old parts of two similar landfills, with waste of different ages. The data sets, which included high data density in both vertical and horizontal directions, were interpreted with 2-D smoothness constrained inversion. The landfills were excavated after the surveying. The objective was to test the capability of the resistivity method as a pre-characterization technique. The objectives were only partially fulfilled. First, the moisture content was the parameter that appeared to exert the dominant control over the resistivity distribution of the landfill. The most important potential information that can be recovered is, therefore, an indication of the waste piles hydraulics. Second, it was neither possible to estimate the amount of recoverable soils, nor to correlate the type of waste with the resistivity models. However, discrete anomalies were identified, and if specific materials are searched for, the resistivity models indicate possible places to search.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Development genes and evolution 210 (2000), S. 157-161 
    ISSN: 1432-041X
    Keywords: Key words Swallow ; bicoid ; Drosophila ; mRNA localization ; Oogenesis ; Embryogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  We analyzed a functional homologue of the swallow gene from Drosophila pseudoobscura. The swallow gene of D. melanogaster plays an essential role in localizing bicoid mRNA in oocytes, and swallow mutant embryos show anterior pattern defects that result from the lack of localization of the bicoid morphogen. The pseudoobscura homologue rescues the function of swallow mutants when introduced into the genome of D. melanogaster, and its expression is similar to that of the melanogaster gene. The predicted pseudoobscura and melanogaster proteins are 49% identical and 69% conserved. The coiled-coil domain previously identified in the melanogaster swallow protein is strongly conserved in the pseudoobscura homologue, but the weak similarity of the melanogaster swallow protein to the RNP class of RNA-binding proteins is not conserved in the pseudoobscura homologue. These and other observations suggest a structural role for swallow in localizing bicoid mRNA, perhaps as part of the egg cytoskeleton.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Development genes and evolution 210 (2000), S. 190-199 
    ISSN: 1432-041X
    Keywords: Key words Ventral neuroectoderm ; Cell shape ; Achaete-scute complex ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  In the embryonic ventral neuroectoderm of Drosophila melanogaster the proneural genes achaete, scute, and lethal of scute are expressed in clusters of cells from which the neuroblasts delaminate in a stereotyped orthogonal array. Analyses of the ventral neuroectoderm before and during delamination of the first two populations of neuroblasts show that cells in all regions of proneural gene activity change their form prior to delamination. Furthermore, the form changes in the neuroectodermal cells of embryos lacking the achaete-scute complex, of embryos mutant for the neurogenic gene Delta, and of embryos overexpressing l’sc suggest that these genes are responsible for most of the morphological alterations observed.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 15
    ISSN: 1432-1211
    Keywords: Key words Vβ13 ; CD4/CD8 ratio ; Rat ; Tcrb ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three rat BV13S1 alleles (T-cell receptor β-chain variable gene 13) were characterized by new BV13S1-allele specific monoclonal antibodies (18B1 and 17D5) and sequence analysis of expressed and genomic BV13S1. Two alleles were functional and designated BV13S1A1 present in strains LEW, BUF, PVG, and BV13S1A2 present in BN and WF. Their products differed by six amino acids, two of them in complementarity-determing region (CDR)1 and one in CDR2. A third nonfunctional allele, BV13S1A3P, was found in strains F344 and DA. Apart from a single nucleotide insertion, it was identical to BV13S1A2. All 12 rat strains tested showed association of TCRBC1 with BV8S2/4 alleles but not with the BV13S1 alleles, which may reflect a different gene order of the rat BV compared to mouse. BV13S1A1-encoded T-cell receptors (TCRs) which bind both monoclonal antibody (mAb) 18B1 and mAb 17D5 are over-represented in the CD4 lymphocyte subset. BV13S1A2-encoded TCRs which are stained by mAb 18B1 but not by mAb 17D5 show a slight CD8-biased expression. Preferential usage of BV13S1A1-positive TCRs by CD4 but not by CD8 cells in (LEW×WF)F1 hybrids and cosegregation of BV13SA1 and increased frequency of BV13S1 TCR-positive CD4 cells in a (LEW×BN)×BN backcross suggest structural differences of the two allelic products as the reason for their contrasting CD4/CD8 subset bias.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 16
    ISSN: 1432-119X
    Keywords: Endothelin-A receptor ; Endothelin-B receptor ; Rat ; Pulmonary fibrosis ; Immunohistochemistry ; Quantitative PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: AbstractPulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Ecological research 15 (2000), S. 93-100 
    ISSN: 1440-1703
    Keywords: aggregation ; coexistence ; Drosophila ; parasitism ; patch size
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: We carried out field experiments to investigate the coexistence of Drosophila species in domestic and forest areas on the basis of the aggregation model. Three cosmopolitan species Drosophila simulans Sturtevant, Drosophila melanogaster Meigen and Drosophila immigrans Sturtevant, and a native species, Drosophila auraria Peng, emerged abundantly from banana placed at the domestic station, while Drosophila immigrans and five native species, Drosophila lutescens Okada, Drosophila rufa Kikkawa and Peng, Drosophila bizonata Kikkawa and Peng, Drosophila sternopleuralis Okada and Kurokawa and Scaptodrosophila coracina (Kikkawa and Peng), were abundant at the forest station. The present analysis suggests that their coexistence was facilitated by the aggregation mechanism. In the cosmopolitan species, the density of individuals that emerged from patches increased with the increase of patch size, but the relationship between fly density and patch size was not clear in the native species. This difference in distribution patterns between the cosmopolitan and native species is likely to be due to the difference in the female visiting behavior. In the present analysis, however, it was not clear whether patch size diversity facilitated their coexistence or not. The effect of patch size diversity may have been masked, because the effect of aggregation was more prominent. The rate of parasitism by wasps was high in October at the domestic station, and in May and June at the forest station. The present result suggests that the rate of parasitism was density-dependent, at least at the domestic station, and therefore parasitism facilitates the coexistence of drosophilid species in domestic areas.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 18 (2000), S. 373-381 
    ISSN: 1573-0646
    Keywords: clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 19
    ISSN: 1573-899X
    Keywords: Memory ; suppression of courting ; Drosophila ; mutants ; P insertion mutagenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Four lines were selected from a collection of 33 lines prepared by P insertion mutagenesis using a single-copy P-element system; the males of these four lines showed memory defects after acquisition of conditioned reflex suppression of courting. In two lines (P171 and P95), the dynamics of retention of the conditioned reflex in the repeated impregnated-female courting test were similar to those of known short-term memory mutantsdnc andrut. In line P153, the dynamics were more reminiscent of the memory dynamics in a known medium-term memory mutant,amn. In line P124, the learning index was insignificant immediately after training was completed, which may indicate that this line was unable to acquire conditioned reflex suppression of courting. Determination of the positions of the P elements (P171: 48A-B; P153: 49B-C; P124; 67B–68A; P95: 77C-D) showed no correspondence with previously known mutations producing memory lesions.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Genetica 109 (2000), S. 35-44 
    ISSN: 1573-6857
    Keywords: Drosophila ; heterochromatin ; imprinting ; parental effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Genetic imprinting is a form of epigenetic silencing. But with a twist. The twist is that while imprinting results in the silencing of genes, chromosome regions or entire chromosome sets, this silencing occurs only after transmission of the imprinted region by one sex of parent. Thus genetic imprinting reflects intertwined levels of epigenetic and developmental modulation of gene expression. Imprinting has been well documented and studied in Drosophila, however, these studies have remained largely unknown due to nothing more significant than differences in terminology. Imprinting in Drosophilais invariably associated with heterochromatin or regions with unusual chromatin structure. The imprint appears to spread from imprinted centers that reside within heterochromatin and these are, seemingly, the only regions that are normally imprinted in Drosophila. This is significant as it implies that while imprinting occurs in Drosophila, it is generally without phenotypic consequence. Hence the evolution of imprinting, at least in Drosophila, is unlikely to be driven by the function of specific imprinted genes. Thus, the study of imprinting in Drosophilahas the potential to illuminate the mechanism and biological function of imprinting, and challenge models based solely on imprinting of mammalian genes.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 21
    ISSN: 1573-6857
    Keywords: centromere ; heterochromatin ; non B-DNA structures ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The molecular basis of centromere formation in a particular chromosomal region is not yet understood. In higher eukaryotes, no specific DNA sequence is required for the assembly of the kinetochore, but similar centromeric chromatins are formed on different centromere DNA sequences. Although epigenesis has been proposed as the main mechanism for centromere specification, DNA recognition must also play a role. Through the analysis of Drosophilacentromeric DNA sequences, we found that dodeca satellite and 18HT satellite are able to form unusual DNA structures similar to those formed by telomeric sequences. These findings suggest the existence of a common centromeric structural DNA motif which we feel merits further investigation.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 22
    ISSN: 1573-6857
    Keywords: Drosophila ; brown eye ; eye pigments ; fitness ; gene localization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract By analyzing the progeny of crosses involving brown eye mutants and the wild types in two members of Drosophila nasuta subgroup namely D. n. nasuta and D. n. albomicans we could show that the mutant gene is recessive, located in the chromosome 2 and the alleles of this gene are present at different loci. A study of fitness in the eye color mutants in comparison with the wild types revealed that D. n. nasuta mutant has higher viability at both 25 ± 1°C and ambient temperatures; while D. n. albomicans mutant has faster rate of development only at 25 ± 1°C. Quantitative analysis of eye pigments in the mutants revealed that there is biosynthesis of both pteridines and xanthommatins unlike in bw/bw of D. melanogaster, where only xanthommatins are synthesized. In both the species, the pteridine quantities in mutants are similar; whereas xanthommatin quantity in $$\user1{bw}_n \user1{/bw}_n$$ is 10 times higher than that of $$\user1{bw}_a \user1{/bw}_a$$ . Further, the F1 progeny of intraspecific crosses (wild type X mutant) are found to have high amounts of pteridine, even when compared with parental wild type.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 23
    ISSN: 1573-6857
    Keywords: DmNop56 ; DsNop56 ; Drosophila ; molecular evolution ; snoRNPs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Small nucleolar RNAs (snoRNAs) are trans‐acting factors involved in maturation of rRNA and have been classified into Box C/D and Box H/ACA families. Most of the snoRNAs occur as ribonucleoprotein complexes with snoRNA‐associated proteins (snoRNPs). All Box C/D snoRNAs in yeast form complexes with Nop1p, Nop56p and Nop58p. Similarly, it has been reported that Box H/ACA‐containing snoRNAs form complexes with yeast Gar1p. Nop56p and Nop58p homologs have been described in several species. Here we report the isolation and molecular characterization of the Dnop56 genes from D. melanogaster and D. subobscura which show a very similar structure. Drosophila Nop56p proteins contain lysine‐rich regions at their carboxy‐terminus, and show a high degree of similarity to other Nop56p proteins from different organisms. Phylogenetic relationships among these proteins and other snoRNPs have been established.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 24
    ISSN: 1573-675X
    Keywords: Apoptosis ; calmodulin ; caspases ; cell line ; Drosophila ; neuron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This study was undertaken to reveal apoptotic pathways in neurons using a Drosophila neuronal cell line derived from larval central nervous system. We could induce apoptotic cell death in the cells by a Ca2+ ionophore (A23187), a protein kinase inhibitor (H-7), an RNA synthesis inhibitor (actinomycin D) and a protein synthesis inhibitor (cycloheximide). All the apoptosis induced by each chemical required Ca2+ ions, although the origin of Ca2+ ions were different: apoptosis induced by A23187 was dependent on extracellular Ca2+ ions whereas those by the other three chemicals utilized intracellular Ca2+ ions. Furthermore, different reactions to W-7, a calmodulin inhibitor, were found: W-7 prevented the cell death by each of the three chemicals but not by A23187. Based on the results, we proposed that the apoptotic pathways are classified into two types in individual cells. One pathway induced by H-7, actinomycin D or cycloheximide is calmodulin-dependent (pathway H), and another induced by A23187 is calmodulin-independent (pathway A).
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 25
    ISSN: 1573-6857
    Keywords: Drosophila ; , esterase-6 ; function ; sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In most lineages of the subgenus Sophophora esterase-6 is a homodimeric haemolymph protein. In the melanogaster subgroup of species it has become a monomer which is mainly expressed in the male sperm ejaculatory duct. Our analyses of esterase-6 sequences from three melanogaster subgroup species and two close relatives reveal a brief period of accelerated amino acid sequence change during the transition between the ancestral and derived states. In this period of 2–6Myr the ratio of replacement to silent site substitutions (0.51) is about three times higher than the values in other lineages of the phylogeny. There are about 50 more replacements in this period than would be predicted from the ratios of replacement to silent site substitutions found elsewhere in the phylogeny. Modelling on the known structure of a related acetylcholinesterase suggests that an unusually high proportion of the replacements in the transitional branch are non-conservative changes on the protein surface. Up to half the accelerated replacement rate can be accounted for by clusters of changes to the face of the molecule containing the opening of the active site gorge. This includes changes in and around regions homologous to peripheral substrate binding sites in acetylcholinesterase. There are also three changes in glycosylation status. One region predicted to lie on the protein surface which becomes markedly more hydrophilic is proposed to be the ancestral dimerisation site that is lost in the transitional branch.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 26
    ISSN: 1573-6857
    Keywords: chromatin structure ; Drosophila ; mutagenic effect ; retroelements ; white
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Transposable elements represent a large fraction of eukaryotic genomes and they are thought to play an important role in chromatin structure. ZAMand Idefixare two LTR-retrotransposons from Drosophila melanogastervery similar in structure to vertebrate retroviruses. In all the strains where their distribution has been studied, ZAMappears to be present exclusively in the intercalary heterochromatin while Idefixcopies are mainly found in the centromeric heterochromatin with very few copies in euchromatin. Their distribution varies in a specific strain called RevI in which the mobilization of ZAMand Idefixis highly induced. In this strain, 15 copies of ZAMand 30 copies of Idefixare found on the chromosomal arms in addition to their usual distribution. Amongst the loci where new copies are detected, a hotspot for their insertion has been detected at the whitelocus where up to four elements occurred within a 3-kb fragment at the 5′ end of this gene. This property of ZAMand Idefixto accumulate at a defined site provides an interesting paradigm to bring insight into the effect exerted by multiple insertions of transposable elements at an euchromatic locus.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 27
    ISSN: 1573-6857
    Keywords: adaptation ; Drosophila ; hydrocarbons ; latitude ; longitude ; natural populations ; polymorphism ; temperaturey ; vapour pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 7-tricosene (7T) and 7-pentacosene (7P) are the major components of cuticular hydrocarbons in Drosophila simulans and D. melanogaster males. A chemical study of 16 isofemale lines of D. melanogaster sampled at the first and eighth generations in laboratory conditions showed the stability of chromatographical profiles. Then a large scale study of male 7T/7P polymorphism was performed with 85 populations of D. melanogaster and 29 of D. simulans collected all over the world. There were significant correlations of the values of the balanced ratio (7T − 7P)/(7T + 7P) with geo-climatic parameters, such as latitude, longitude, mean temperature, temperature range and vapour pressure. Parallel variations were also reported for the homologous linear alkanes (23 and 25 Carbon atoms) but not for the longer branched alkanes (27 and 29 Carbon atoms). No correlation was significant for the D. simulans populations studied. In this species a similar polymorphism of 7T/7P was found but restricted to a few populations from West Equatorial Africa.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 28
    ISSN: 1573-6857
    Keywords: biophysics ; body size ; Drosophila ; ectotherm ; genetic variance ; stress ; temperature extreme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract An increase in genetic variation in body size has often been observed under stress; an increase in dominance variance and interaction variance as well as in additive genetic variance has been reported. The increase in genetic variation must be caused by physiological mechanisms that are specific to adverse environments. A model is proposed to explain the occurrence of an increase in genetic variation in body size in Drosophila at extreme temperatures. The model has parameters specific to the low- and high-temperature regions of the viable range. Additive genetic variation in the boundary temperatures leads to a marked increase in additive genetic variation in development rate and body size at extreme temperatures. Additive genetic variation in the temperature sensitivity in the low- and high-temperature regions adds non-additive genetic variation. Development rate shows patterns in additive genetic variation that differ from the patterns of genetic variation in body size; therefore, the genetic correlation between development rate and body size changes sign repeatedly as a function of temperature. The existence of dominance in the genetic variation in the boundary temperatures or in the low- and high-temperature sensitivities leads to a higher total genetic variance due to higher dominance and interaction variance, for both development rate and body size.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 29
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 30
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 31
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 32
    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 33
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 34
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 35
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 36
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 37
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 38
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 39
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 40
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 17 (2000), S. 903-905 
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 41
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 17 (2000), S. 127-134 
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 42
    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 43
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 44
    ISSN: 1617-4623
    Keywords: Key words AP-3 ; Biogenesis ; Pigment granule ; Synaptic vesicle ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The AP-3 adaptor protein complex has been implicated in the biogenesis of lysosome-related organelles, such as pigment granules/melanosomes, and synaptic vesicles. Here we compare the relative importance of AP-3 in the biogenesis of these organelles in Drosophila melanogaster. We report that the Drosophila pigmentation mutants orange and ruby carry genetic lesions in the σ3 and β3-adaptin subunits of the AP-3 complex, respectively. Electron microscopy reveals dramatic reductions in the numbers of electron-dense pigment granules in the eyes of these AP-3 mutants. Mutant flies also display greatly reduced levels of pigments housed in these granules. In contrast, electron microscopy of retinula cells reveals numerous synaptic vesicles in both AP-3 mutant and wild-type flies, while behavioral assays show apparently normal locomotor ability of AP-3 mutant larvae. Together, these results demonstrate that Drosophila AP-3 is critical for the biogenesis of pigment granules, but is apparently not essential for formation of a major population of synaptic vesicles in vivo.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 45
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 28 (2000), S. 128-134 
    ISSN: 1573-9686
    Keywords: Hippocampus ; Vigilance states ; Paired-pulse ; Dentate gyrus ; Dentate granule cells ; Evoked response ; Rat ; In vivo studies ; Perforant path ; Maturation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract This study examined the effect of normal development and vigilance state on the modulation of dentate granule cell activity in the freely moving rat at 15, 30, and 90 days of age across three vigilance states: quiet waking, slow-wave sleep, and rapid eye movement sleep. Using paired-pulse stimulation, the paired-pulse index (PPI) was obtained for the dentate evoked field potentials elicited by the stimulation of the medial perforant path. Although significant differences in PPI values were observed during development, no significant vigilance state related changes were obtained. Preweaning infant rats, i.e., 15-day old, exhibited significantly less early (interpulse intervals, IPI= 20–50 ms) and late (IPI = 300–1000 ms) inhibition, and less facilitation (IPI = 50–150 ms) when compared to the 90-day old adult rats during all three vigilance states. PPI values obtained from the 30-day old group fell intermediate between the 15- and 90-day old animals. These changes in PPI values provide a quantitative measure of changes in the modulation of dentate granule cell excitability during normal maturation. They can now can be used to evaluate the impact of various insults, such as prenatal protein malnutrition or neonatal stress, on hippocampal development. © 2000 Biomedical Engineering Society. PAC00: 8717Nn, 8719La, 8719Nn
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 46
    ISSN: 1573-9686
    Keywords: Heart ; Left ventricle ; LV contractility ; ESPVR ; Pig ; Rat ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The end systolic pressure–volume relation (ESPVR) has been shown to be a relatively load independent measure of left ventricular (LV) contractility. Recently, several single-beat ESPVR computation methods have been developed, enabling the quantification of LV contractility without the need to alter vascular loading conditions on the heart. Using a single-beat ESPVR method, which has been validated previously in humans and assumes that normalized elastance is constant between individuals of a species, we studied the effects of myocardial infarction on LV contractility in two species, the rat and the pig. In our studies, LV pressure was acquired invasively and LV volume determined noninvasively with magnetic resonance imaging, at one week postinfarction in pigs and at 12 weeks postinfarction in rats. Normalized systolic elastance curves in both animal species were not statistically different from that of humans. Also, the slope of the ESPVR $$\left( {E_{es} } \right)$$ decreased significantly following infarction in both species, while the volume-axis intercept $$\left( {V_0 } \right)$$ was unaffected. These results indicate that a single-beat ESPVR method can be used to measure the inotropic response of the heart to myocardial infarction, and that the basis for this method (i.e., constant normalized elastance) is applicable to a variety of mammalian species. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 8761Lh, 8719Hh, 8719Rr, 8719Ff
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 47
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 28 (2000), S. 1101-1115 
    ISSN: 1573-9686
    Keywords: Time–frequency analysis ; Coherence ; Cross correlation ; Nonstationary persistent signals ; Central pattern generator ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract We present a novel time-varying phase spectrum (TVPS) method to quantify the dynamics of coevolution of two persistent nonstationary coupled signals. Based on the TVPS, an instantaneous intersignal phase shift is defined within the primary frequency range in which the two signals are highly correlated. The TVPS is estimated using a fixed-window method or an adaptive-window method. In the latter method, the window length changes dynamically and automatically as a function of change in frequency of the signals. The effects of altering window types and lengths on the accuracy of the estimation of the primary phase shift is assessed by analyzing synthesized linear chirp signals with decaying amplitude and constant relative phase shift or decaying amplitude and changing relative phase shifts. The methods developed are also used for determining the evolution of the primary phase shift among ventral root activities during fictive locomotion in an in vitro rat spinal cord preparation. The analyses indicate that the TVPS method in conjunction with the determination of the primary frequency range, allows determination of both the evolution of the coupling strength and the evolution of the phase shift between two persistent nonstationary rhythmic signals in the joint time–frequency domain. An adaptive window reduces the estimation bias and the estimation variability. © 2000 Biomedical Engineering Society. PAC00: 0230-f, 8780Tq
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 48
    Electronic Resource
    Electronic Resource
    Springer
    Fish physiology and biochemistry 23 (2000), S. 225-232 
    ISSN: 1573-5168
    Keywords: methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 49
    ISSN: 1573-6857
    Keywords: Drosophila ; heterochromatin ; telomere ; transcription ; transposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Chromosome length in Drosophilais maintained by the targeted transposition of two families of non-LTR retrotransposons, HeT-Aand TART. Although the rate of transposition to telomeres is sufficient to counterbalance loss from the chromosome ends due to incomplete DNA replication, transposition as a mechanism for elongating chromosome ends raises the possibility of damaged or deleted telomeres, because of its stochastic nature. Recent evidence suggests that HeT-Atransposition is controlled at the levels of transcription and reverse transcription. HeT-Atranscription is found primarily in mitotically active cells, and transcription of a w +reporter gene inserted into the 2L telomere increases when the homologous telomere is partially or completely deleted. The terminal HeT-Aarray may be important as a positive regulator of this activity in cis, and the subterminal satellite appears to be an important negative regulator in cis. A third chromosome modifier has been identified that increases the level of reverse transcriptase activity on a HeT-A RNA template and greatly increases the transposition of HeT-A. Thus, the host appears to play a role in transposition of these elements. Taken together, these results suggest that control of HeT-Atransposition is more complex than previously thought.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 50
    ISSN: 1573-6849
    Keywords: Adh ; Drosophila ; FISH ; genome evolution ; repleta group
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The molecular organization of a 1.944-Mb chromosomal region of Drosophila melanogaster around the Adh locus has been analyzed in two repleta group species: D. repleta and D. buzzatii. The extensive genetic and molecular information about this region in D. melanogaster makes it a prime choice for comparative studies of genomic organization among distantly related species. A set of 26 P1 phages from D. melanogaster were successfully hybridized using fluorescence in-situ hybridization (FISH) to the salivary gland chromosomes of both repleta group species. The results show that the Adh region is distributed in D. repleta and D. buzzatii over six distant sites of chromosome 3, homologous to chromosomal arm 2L of D. melanogaster (Muller's element B). This observation implies a density of 2.57 fixed breakpoints per Mb in the Adh region and suggests a considerable reorganization of this chromosomal element via the fixation of paracentric inversions. Nevertheless, breakpoint density in the Adh region is three times lower than that estimated for D. repleta chromosome 2, homologous to D. melanogaster 3R (Muller's element E). Differences in the rate of evolution among chromosomal elements are seemingly persistent in the Drosophila genus over long phylogenetic distances.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 51
    Electronic Resource
    Electronic Resource
    Springer
    Genetica 108 (2000), S. 263-267 
    ISSN: 1573-6857
    Keywords: Drosophila ; horizontal transfer ; Minos ; Tc1-like ; Tc1-marinerfamily ; transposable elements ; transposon distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We analyzed 28 species of the genus Drosophilafor the presence of the Tc1-like transposable element Minosusing Southern blot hybridization under high stringency conditions. The Minostransposon was found in members of both the Drosophilaand the Sophophorasubgenus showing a distribution that is wider if compared to other well-studied Drosophilatransposons such as the Pelement, hoboand mariner. The presence of Minos-hybridizing sequences was discontinuous in the Sophophorasubgenus, especially in the melanogasterspecies group. Using the Polymerase Chain Reaction we amplified a portion corresponding to the putative Minostransposase from different Drosophilaspecies. Cloning and sequence analysis of randomly selected Minoscopies from D. mojavensisis, D. saltansand D. willistonisupports the idea that event(s) of horizontal transfer may have contributed to the spreading of this transposon in the Drosophilagenus.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 52
    ISSN: 1573-6857
    Keywords: artificial selection ; atavistic structures ; Drosophila ; pattern formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Artificial selection was carried out for over 45 generations to enhance and suppress expression of the mutation hairy on the Drosophila melanogaster wing. Whole chromosome mapping of X‐linked and autosomal modifiers of sense organ number displayed regional differences in magnitude and direction of their effects. Regional specificity of modifier effects was also seen in some interchromosomal interactions. Scanning electron microscopy allowed precise measurement of sense organ size and position along the L3 longitudinal wing vein. Sense organ size varied in a predictable fashion along the proximal–distal axis, and the dorsal pattern differed from the ventral pattern. The high and low selection lines differed most in the proximal portion of the L3 vein. Extra sense organs in the High line were often associated with vein fragments at locations predicted from ancestral vein patterns. Thus, regional specificity of polygenic or quantitative trait locus modifier effects was identified in several different parts of the wing.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 53
    ISSN: 1573-6857
    Keywords: artificial selection ; Drosophila ; lifespan ; mortality ; paraquat ; DDT ; recovery hypothesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Adult lifespans, age‐specific survival, age‐specific mortality, survival times on paraquat, and survival times on DDT were assayed in seven lines of Drosophila melanogaster, including two genetically heterogeneous wild lines recently collected from nature, and three inbred and recombinant inbred lines derived from an artificial selection experiment for increased lifespan. Survival on paraquat is positively correlated with adult lifespan. DDT resistance is uncorrelated with either paraquat resistance or lifespan. The wild lines are unexceptional with respect to average lifespan, paraquat resistance, age‐specific survivorship, and leveling off of mortality rates at advanced ages, but have high levels of DDT resistance. Cluster analysis groups the wild lines with three unselected laboratory stocks in one cluster, while two long‐lived elite recombinant inbred lines form a second cluster. Long‐lived laboratory‐adapted lines are quantitatively differentiated from the wild stocks, both with respect to average adult lifespans and resistance to an oxidizing agent. We reject the ‘recovery’ hypothesis, which proposes that Drosophila artificially selected for long life have phenotypes that merely recover the wild state.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 54
    Electronic Resource
    Electronic Resource
    Springer
    Journal of bioenergetics and biomembranes 32 (2000), S. 293-300 
    ISSN: 1573-6881
    Keywords: abnormal wing discs ; lethal mutant ; Drosophila ; Killer-of-prune ; prune
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract The abnormal wing discs gene of Drosophila encodes a soluble protein with nucleosidediphosphate kinase activity. This enzymic activity is necessary for the biological function ofthe abnormal wing discs gene product. Complete loss of function, i.e., null, mutations causelethality after the larval stage. Most larval organs in such null mutant larvae appear to benormal, but the imaginal discs are small and incapable of normal differentiation.Killer-of-prune is a neomorphic mutation in the abnormal wing discs gene. It causes dominant lethalityin larvae that lack prune gene activity. The Killer-of-prune mutant protein may have alteredsubstrate specificity. Null mutant larvae have a low level of nucleoside diphosphate kinaseactivity. This suggests that there may be additional Drosophila genes that encode proteinswith nucleoside dipthosphate kinase activity. Candidate genes have been found in theDrosophila genome.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 55
    Electronic Resource
    Electronic Resource
    Springer
    Genetica 109 (2000), S. 105-111 
    ISSN: 1573-6857
    Keywords: Drosophila ; evolution ; heterochromatin ; Y chromosome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Y chromosome evolution is characterized by the expansion of genetic inertness along the Y chromosome and changes in the chromosome structure, especially the tendency of becoming heterochromatic. It is generally assumed that the sex chromosome pair has developed from a pair of homologues. In an evolutionary process the proto-Y-chromosome, with a very short differential segment, develops in its final stage into a completely heterochromatic and to a great extends genetically eroded Y chromosome. The constraints evolving the Y chromosome have been the objects of speculation since the discovery of sex chromosomes. Several models have been suggested. We use the exceptional situation of the in Drosophila mirandato analyze the molecular process in progress involved in Y chromosome evolution. We suggest that the first steps in the switch from a euchromatic proto-Y-chromosome into a completely heterochromatic Y chromosome are driven by the accumulation of transposable elements, especially retrotransposons inserted along the evolving nonrecombining part of the Y chromosome. In this evolutionary process trapping and accumulation of retrotransposons on the proto-Y-chromosome should lead to conformational changes that are responsible for successive silencing of euchromatic genes, both intact or already mutated ones and eventually transform functionally euchromatic domains into genetically inert heterochromatin. Accumulation of further mutations, deletions, and duplications followed by the evolution and expansion of tandem repetitive sequence motifs of high copy number (satellite sequences) together with a few vital genes for male fertility will then represent the final state of the degenerated Y chromosome.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 56
    ISSN: 1573-6857
    Keywords: chromosomal proteins ; Drosophila ; heterochromatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 57
    Electronic Resource
    Electronic Resource
    Springer
    Genetica 109 (2000), S. 25-33 
    ISSN: 1573-6857
    Keywords: chromatin ; Drosophila ; heterochromatin ; position effect variegation ; telomeres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A significant fraction of most eukaryotic genomes is packaged into chromatin that is not permissive for gene expression. This silent chromatin is typically located near centromeres and telomeres and has fascinated scientists for more than 70 years, yet many questions remain unanswered. Part of the difficulties in studying silent chromatin at the molecular level is the repetitive nature of the DNA sequences in these regions. To overcome this problem, Drosophilastocks carrying in vitrodesigned transgenes inserted within silent chromatin have been generated. Molecular analysis of these transgenes has shed light on the nature of the chromatin structure within these regions and provided insights on the mechanisms of gene silencing. This review will focus on recent studies using telomeric transgenes. The results from these studies suggest that nuclear organization plays a role in gene silencing and that silencing is the result of a block early in the process of transcription initiation.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 58
    Electronic Resource
    Electronic Resource
    Springer
    Molecules and cells 10 (2000), S. 61-64 
    ISSN: 0219-1032
    Keywords: Drosophila ; Imprecise Excision ; Null Allele ; P Element ; Rbp9
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The P element has been widely used as a mutagen because of its convenience in locating the site of mutagenesis. However, P element-induced mutations often result in varied mutant phenotypes, making it difficult to identify the null phenotype. Previously, three Rbp9 alleles were isolated using P element mutagenesis. Although the coding regions of Rbp9 were disrupted by P elements in all three cases, they showed different degrees of defects. In order to characterize the null phenotype of Rbp9, Rbp9 alleles with chromosomal deletions were created by inducing imprecise excisions of the P elements. All Rbp9 alleles generated from imprecise excisions showed the same mutant phenotype: female flies were sterile and cystocyte differentiation was blocked. This result reveals that the primary function of Rbp9 resides in the regulation of cystocyte differentiation. In addition, this result shows that a P element does not always completely inactivate gene activity, even when it is incorporated into the coding region.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 59
    ISSN: 0219-1032
    Keywords: Drosophila ; Polycomb Group Genes ; Ultrabithorax ; Visceral Mesoderm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Polycomb group (PcG) genes encode repressors of many developmental regulatory genes including homeotic genes and are known to act by modifying chromatin structure through complex formation. We describe how Ultrabithorax (Ubx) expression is affected by the PcG mutants in the visceral mesoderm. Mutant embryos of the genes extra sex combs (esc), Polycomb (Pc), additional sex combs (Asx) and pleiohomeotic (pho) were examined. In each mutation, Ubx was ectopically expressed outside of their normal domains along the anterior-posterior axis in the visceral mesoderm, which is consistent with the effect of PcG proteins repressing the homeotic genes in other tissues. All of these four PcG mutations exhibit complete or partial lack of midgut constriction. However, two thirds of esc mutant embryos did not show Ubx expression in parasegment 7 (PS7). Even in the embryos showing ectopic Ubx expression, the level of Ubx expression in the PcG mutations was weaker than that in normal embryos. We suggest that in PcG mutations the ectopic Ubx expression is caused by lack of PcG repressor proteins, while the weaker or lack of Ubx expression is due to the repression of Ubx by Abd-B protein which is ectopically expressed in PcG mutations as well.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 60
    ISSN: 0219-1032
    Keywords: Drosophila ; Gene Expression ; JHRE ; Juvenile Hormone ; Male Accessory Gland ; Mst57Dc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mst57Dc has been isolated as a male accessory gland transcript of Drosophila melanogaster. Its product is a secretory protein, which is phosphorylated by protein kinase A. In the present study, the expression pattern of Mst57Dc was analyzed. It is preferentially expressed in but not restricted to the male accessory glands. Other than in the accessory glands, it is slightly expressed in other body parts, including the head and female body. In the accessory glands, a high level of expression was detected right after eclosion when the titer of juvenile hormone III (JHIII) reaches a peak. Its accumulation was increased by mating, which has been known to act via JH. In ap56f, a JH-deficient mutant, the level of Mst57Dc transcripts was about 60% of the wild type. Moreover a JH-responsive element like palindromic sequence and several sequence motifs were found in the 5′ and 3′ flanking regions of Mst57Dc. Taken together, JH is proposed as a regulator of Mst57Dc gene expression.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 61
    ISSN: 0219-1032
    Keywords: c-Fos ; Dopamine ; D1 ; Hippocampus ; Rat ; Synaptic Plasticity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract While dopamine is likely to modulate hippocampal synaptic plasticity, there has been little information about how dopamine affects synaptic transmission in the hippocampus. The expression of IEGs including c-fos has been associated with late phase LTP in the CA1 region of the hippocampus. The induction of c-fos by dopaminergic receptor activation in the rat hippocampus was investigated by using semiquantitative RT-PCR and immuno-cytochemistry. The hippocampal slices which were not treated with dopamine showed little expression of c-fos mRNA. However, the induction of c-fos mRNA was detected as early as 5 min after dopamine treatment, peaked at 60 min, and remained elevated 5 h after treatment. Temporal profiles of increases in c-fos mRNA by R(+)-SKF-38393 (50 μM) and forskolin (50 μM) were similar to that of dopamine. An increase in [cAMP] was observed in dopamine-, SKF-, or forskolin-treated hippocampal slices. By immunocytochemical studies, control hippocampal cells showed little expression of c-Fos immunoreactivity. However, when cells were treated with dopamine, an increase in the expression of c-Fos immunoreactivity was observed after treatment for 2 h. The treatment of hippocampal neurons with R(+)-SKF38393 (50 μM) or forskolin (50 μM) also induced a significant increase in c-Fos expression. These results indicate that the dopamine D1 receptor-mediated cAMP dependant pathway is associated with the expression of c-Fos in the hippocampal neurons. These data are consistent with the possible role of endogenous dopamine on synaptic plasticity via the regulation of gene expression. Furthermore, these results imply that dopamine might control the process of memory storage in the hippocampus through gene expression.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 62
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 17 (2000), S. 1426-1431 
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 63
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 64
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 65
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 66
    ISSN: 1573-904X
    Keywords: benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 67
    ISSN: 1573-3297
    Keywords: Insect ; larval photobehavior ; locomotion ; Drosophila ; behavioral mutants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract A new assay was designed, named checker, that measures the individual response to light in the fruitfly Drosophila melanogaster larva. In this assay the Drosophila larva apparently modulates its pattern of locomotion when faced with a choice between a dark and lit environment by orienting its movement towards the dark environment. We show that, in this assay, a response to light can be measured as an increase in residence time in the dark versus the lit quadrant. Mutations that disrupt phototransduction in the adult Drosophila abolish the larval response to light, demonstrating that this larval visual function is similar to that of the adult fly. Similarly, no response to light was detected in strains where the larval visual system (photoreceptors and target area) was disrupted by a mutation in the homeobox containing gene sine oculis (so) gene. Ablation of photoreceptors by the targeted expression of the cell death gene hid under the control of the photoreceptor-specific transcription factor glass (gl) abolishes this response entirely. Finally, we demonstrate that this response to light can be mediated by rhodopsins other than the blue absorbing Rh1.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 68
    ISSN: 1573-8221
    Keywords: acylprolyldipeptide ; GVS-111 ; pharmacokinetics ; blood-brain barrier permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an umodified state.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 69
    Electronic Resource
    Electronic Resource
    Springer
    Medical & biological engineering & computing 38 (2000), S. 42-48 
    ISSN: 1741-0444
    Keywords: Bowel sounds ; Rat ; Motility ; Body acoustics ; Signal detection ; Signal characterisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This study is aimed at detecting gastrointestinal sounds (GIS) and correlating their characteristics with gastrointestinal (GI) conditions. The central hypotheses are that GIS generation depends on the motility patterns and the mechanical properties of the gut, and that changes in those result in measurable differences in GIS. An animal model which included both healthy rats and those with small bowel obstruction (SBO) was developed. The acoustic bursts, of GIS were detected by amplitude thresholding the signal envelope. Three methods of envelope estimation were proposed and evaluated. Envelope estimation using a Hilbert transform was found to produce the best results in the current application. The duration and dominant frequency of each detected GIS event was estimated and clear differences between healthy and diseased rats were discovered. In the control state, GIS events were found to consistently be of relatively short duration (3–65ms). Although the majority of events in the SBO state had similar short duration, infrequent longer events were also detected and appeared to be pathognomonic. Long duration events (〉100 ms) occurred in each of seven obstructed, but in none of 14 non-obstructed, cases (p〈0.001). It is concluded that GIS analysis may prove useful in the non-invasive, rapid, and accurate diagnosis of SBO.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 70
    Electronic Resource
    Electronic Resource
    Springer
    Risk analysis 19 (1999), S. 711-726 
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 71
    ISSN: 1539-6924
    Keywords: MeHg ; pharmacokinetics ; PBPK model ; variability ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 μg/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 μg/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 μg/kg/day and an MRL of 0.3 μg/kg/day.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 72
    Electronic Resource
    Electronic Resource
    Springer
    Animal cognition 2 (1999), S. 123-129 
    ISSN: 1435-9456
    Keywords: Key words Face recognition ; Inversion ; Expertise ¶effect ; Matching-to-sample ;  Macaca mulatta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract This study investigated the face inversion effect in rhesus monkeys (Macaca mulatta). Face stimuli consisted of ten black-and-white examples of unfamiliar rhesus monkey faces, brown capuchin faces, and human faces. Two non-face categories included ten examples of automobiles and abstract shapes. All stimuli were presented in a sequential matching-to-sample format using an automated joystick-testing paradigm. Subjects performed significantly better on upright than on inverted presentations of automobiles, rhesus monkey and capuchin faces, but not human faces or abstract shapes. These results are inconsistent with data from humans and chimpanzees that show the inversion effect only for categories of stimuli for which subjects have developed expertise. The inversion effect in rhesus monkeys does not appear to be face-specific, and should therefore not be used as a marker of specialized face processing in this species.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 73
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 90 (1999), S. 175-181 
    ISSN: 1570-7458
    Keywords: Olfactory response ; Drosophila ; menthol ; bioassay ; trap assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A modification of the trap assay (Woodard et al., 1989) was used to evaluate the response of Drosophila melanogaster (Meigen) to food media containing menthol. Dose-response curves for flies to mentholic foods were produced for flies that had been pre-exposed to menthol, during development and adult life, and flies that had not been exposed to menthol before the assay. Mentholic food media were less attractive to Drosophila than plain food medium. Rearing flies on a medium containing menthol reduced their aversion to some concentrations of menthol. The rearing effect was not simply due to lowered general activity levels resulting from developing in a medium containing menthol. There was a threshold concentration of menthol in the rearing medium below which we found no induced behavioural change.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 74
    ISSN: 1432-041X
    Keywords: Key words bHLH genes ; Drosophila ; Embryogenesis ; Enhancer of split ; Notch pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  E(spl) bHLH genes are targets of the Notch pathway: they are transcriptionally activated in response to the Notch signal. Yet, during imaginal development, additional regulatory factors appear to modulate transcription resulting in different expression patterns. During early embryogenesis all E(spl) bHLH genes are expressed in roughly the same domain, namely the neurogenic ectoderm. Within this region these seven genes show a highly dynamic, yet distinct transcriptional activity. Our analysis further detected tissue specific expression of some E(spl) genes at later embryonic stages. Prominent differences were observed in the dorsolateral and procephalic neuroectodermal regions as well as in the mesoderm. These observations indicate that other factors in addition to the Notch signal participate in the regulation of the individual E(spl) genes not only in imaginal tissues but also during neuroblast specification and other cell fate determination events in the embryo.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 75
    ISSN: 1432-041X
    Keywords: Key words Delta ; Notch ; Follicle cells ; Oogenesis ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  During Drosophila oogenesis the body axes are determined by signaling between the oocyte and the somatic follicle cells that surround the egg chamber. A key event in the establishment of oocyte anterior-posterior polarity is the differential patterning of the follicle cell epithelium along the anterior-posterior axis. Both the Notch and epithelial growth factor (EGF) receptor pathways are required for this patterning. To understand how these pathways act in the process we have analyzed markers for anterior and posterior follicle cells accompanying constitutive activation of the EGF receptor, loss of Notch function, and ectopic expression of Delta. We find that a constitutively active EGF receptor can induce posterior fate in anterior but not in lateral follicle cells, showing that the EGF receptor pathway can act only on predetermined terminal cells. Furthermore, Notch function is required at both termini for appropriate expression of anterior and posterior markers, while loss of both the EGF receptor and Notch pathways mimic the Notch loss-of-function phenotype. Ectopic expression of the Notch ligand, Delta, disturbs EGF receptor dependent posterior follicle cell differentiation and anterior-posterior polarity of the oocyte. Our data are consistent with a model in which the Notch pathway is required for early follicle cell differentiation at both termini, but is then repressed at the posterior for proper determination of the posterior follicle cells by the EGF receptor pathway.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 76
    ISSN: 1432-041X
    Keywords: Key words Synapse ; Drosophila ; Immunoglobulin superfamily ; Axonal transport ; Neurosecretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Hikaru genki (HIG) is a putative secreted protein of Drosophila that belongs to immunoglobulin and complement-binding protein superfamilies. Previous studies reported that, during pupal and adult stages, HIG protein is synthesized in subsets of neurons and appears to be secreted to the synaptic clefts of neuron-neuron synapses in the central nervous system (CNS). Here we report the analyses of distribution patterns of HIG protein at embryonic and larval stages. In embryos, HIG was mainly observed in subsets of neurons of the CNS that include pCC interneurons and RP5 motorneurons. At third instar larval stage, this protein was detected in a limited number of cells in the brain and ventral nerve cord. Among them are the motorneurons that extend their axons to make neuromuscular junctions on body wall muscle 8. Immunoelectron microscopy showed that these axonal processes as well as the neuromuscular terminals contain numerous vesicles with HIG staining, suggesting that HIG is in a pathway of secretion at this stage. Some neurosecretory cells were also found to express this protein. These data suggest that HIG functions in the nervous system through most developmental stages and may serve as a secreted signalling molecule to modulate the property of synapses or the physiology of the postsynaptic cells.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 77
    Electronic Resource
    Electronic Resource
    Springer
    Development genes and evolution 209 (1999), S. 218-225 
    ISSN: 1432-041X
    Keywords: Key words α-catenin ; Drosophila ; Green fluorescent protein (GFP) ; Adherens junction ; Epithelial morphogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Cell-cell adherens junctions (AJs), comprised of the cadherin-catenin adhesion system, contribute to cell shape changes and cell movements in epithelial morphogenesis. However, little is known about the dynamic features of AJs in cells of the developing embryo. In this study, we constructed Dα-catenin fused with a green fluorescent protein (Dα-catenin-GFP), and found that it targeted apically located AJ-based contacts but not other lateral contacts in epithelial cells of living Drosophila embryos. Using time-lapse fluorescence microscopy, we examined the dynamic performance of AJs containing Dα-catenin-GFP in epithelial morphogenetic movements. In the ventral ectoderm of stage 11 embryos, concentration and deconcentration of Dα-catenin-GFP occurred concomitantly with changes in length of AJ contacts. In the lateral ectoderm of embryos at the same stage, dynamic behaviour of AJs was concerted with division and delamination of sensory organ precursor (SOP) cells. Moreover, changes in patterns of AJ networks during tracheal extension could be followed. Finally, we utilized Dα-catenin-GFP to precisely observe the defects in tracheal fusion in shotgun mutants. Thus, the Dα-catenin-GFP fusion protein is a helpful tool to simultaneously observe morphogenetic movements and AJ dynamics at high spatio-temporal resolution.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 78
    ISSN: 1432-041X
    Keywords: Key words Deformed ; Drosophila ; Embryogenesis ; Tribolium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  We have analyzed the Tribolium castaneum ortholog of the Drosophila homeotic gene Deformed (Dfd) and determined its expression pattern during embryogenesis in this beetle. Tc Deformed (Tc Dfd) is expressed in the blastoderm and the condensing germ rudiment in a region that gives rise to gnathal segments. During germ band extension Tc Dfd is expressed in the mandibular and maxillary segments, their appendages, and the dorsal ridge. Comparison of insect Dfd protein sequences reveals several highly conserved regions. To determine whether common molecular features reflect conserved regulatory functions we used the Gal4 system to express the Tribolium protein in Drosophila embryos. When Tc Dfd is expressed throughout embryonic ectoderm under the control of P69B, the beetle protein autoregulates the endogenous Dfd gene. In addition, the Drosophila proboscipedia gene (a normal target of Dfd) is ectopically activated in the antennal and thoracic segments. We also compared the ability of the beetle and fly proteins to rescue defects in Dfd – mutants by expressing each throughout the embryonic during embryogenesis. Both proteins rescued Dfd – defects to the same extent in that they each restore the development of mouth hooks and cirri, as well as cause gain-of-function abnormalities of posterior mouth parts. As before, pb was ectopically activated in the antennal segment. This is the first demonstration of the ability of a heterologous homeotic selector protein to directly regulate a target gene independent of an endogenous Drosophila autoregulatory loop.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 79
    ISSN: 1432-1211
    Keywords: Key words Class II MHC sequence ; Rat ; Cloning ; RT-PCR ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 80
    Electronic Resource
    Electronic Resource
    Springer
    Molecular biology reports 26 (1999), S. 103-111 
    ISSN: 1573-4978
    Keywords: arthropod ; crustacean ; Drosophila ; insect ; lobster ; multicatalyic proteinase ; proteasome ; ubiquitin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Recent work on structural/functional relationships in arthropod proteasomes is reviewed. Taking advantage of our ability to induce a stable, proteolytically-active conformation of the lobster proteasome, the structures of basal and heat-activated complexes were probed with exogenous proteases. Increased sensitivity to chymotrypsin and trypsin showed that heat activation induced a more ‘open’ conformation, allowing entry of large substrates into the catalytic chamber. In Drosophila, the effects of two developmental mutant alleles (DTS-7 and DTS-5) encoding proteasome subunits (Z and C5, respectively) on the subunit composition and catalytic activities of the enzyme were examined. Both qualitative and quantitative differences in compositions between wild-type (+/+) and heterozygotes (+/DTS) indicated that incorporation of mutant subunits alters post-translational modifications of the complex. Catalytic activities, however, were similar, which suggests that the developmental defect involves other proteasome properties, such as intracellular localization and/or interactions with endogenous regulators. A hypothetical model in which DTS subunits act as poison subunits is presented.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 81
    Electronic Resource
    Electronic Resource
    Springer
    Molecular biology reports 26 (1999), S. 147-157 
    ISSN: 1573-4978
    Keywords: Drosophila ; jun ; fos ; AP-1 ; transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The mammalian proto-oncogenes c-jun and c-fos are situated at the end of multiple signal transduction pathways and activation of their products Jun and Fos, components of the transcription factor AP-1, are able to regulate gene transcription in response to extracellular stimuli. Djun and Dfos, the products of the Drosophila proto-oncongenes Djun and Dfos, are similar in size and sequence to their mammalian counterparts c-Jun and c-Fos and are related to their mammalian counterparts by their antigenic properties. However, very little is known about how they are regulated through signal transduction pathways. This paper has investigated the response of their mRNA abundance levels to three signal transduction pathways in Drosophila cultured cells. Various agonists and anagonists that stimulate and inhibit specific enzymes in the pathways have been tested. The results suggest that Djun and Dfos mRNA are continuously expressed and their abundance levels are transiently regulated by multiple signaling pathways, the peak response coming at 1–2 hours after perturbation. Dfos is more highly regulated than Djun which is only modulated. The receptor tyrosine kinase pathways positively regulate Dfos and Djun. The cAMP-mediated pathway positively regulates Dfos but negatively regulates Djun. The protein kinase C-activated pathway does not affect Djun whereas it negatively regulates Dfos.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 82
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 296 (1999), S. 235-246 
    ISSN: 1432-0878
    Keywords: Key words Transplantation ; Parkinson’s disease ; CNS fetal development ; CNS differentiation ; Neurotrophic factors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have previously shown that a combination of the cytokines interleukin (IL)-1, IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF) can convert rat fetal (E14.5) mesencephalic progenitor cells into tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in vitro. The experiments described here characterize the mesencephalic progenitor cells and their cytokine-induced conversion into dopamine (DA) neurons. For all experiments, we used bromodeoxyuridine (BrdU)-ir cultures of (E14.5) mesencephalic progenitor cells that had been expanded at least 21 days. We first demonstrated that IL-1 induced DA neuron conversion in mesencephalic progenitors, but not in striatal progenitors (P〈0.001). Thus, these cells should be classified as lineage-restricted progenitors, and not omnipotent stem cells. To further characterize cell populations in these cultures, we used monoclonal antibodies against Hu (an early marker for neurons), growth-associated protein (GAP)-43 (a marker for neuronal process extension), TH (a marker for DA neurons), and glial fibrillary acidic protein (GFAP, a marker for astrocytes). We assessed (E14.5) mesencephalic progenitor cell cultures (plated at 125,000 cells/cm2) incubated in the cytokine mixture (described above) or in complete media (CM, negative control). Following 7 days incubation, GFAP-positive cells formed a nearly confluent carpet in both types of cultures. However, numbers of Hu-ir and GAP-43-ir cells in the cytokine-incubated cultures far exceeded those in CM-incubated controls (P=0.0003, P=0.0001, respectively), while numbers of TH-ir cells were 58-fold greater in the cytokine-incubated cultures versus CM-incubated controls. The TH phenotype persisted for 7 days following withdrawal of the differentiation media. Numerous double-labeled cells that were BrdU-ir and also TH-ir, or Hu-ir and also TH-ir, were observed in the cytokine-incubated cultures. These data suggest that cytokines ”drive” the conversion of progenitor cells into DA neurons.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 83
    ISSN: 1432-0878
    Keywords: Key words Subcommissural organ ; Isograft ; Xenograft ; Reissner’s fiber ; Cerebrospinal fluid ; Rat ; Bovine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The subcommissural organ (SCO) secretes glycoproteins into the cerebrospinal fluid (CSF) that aggregate and form Reissner’s fiber (RF). The factors involved in this aggregation are not known. One factor may be the hydrodynamics of the CSF when flowing through the aqueduct. This hypothesis was tested by isografting rat SCO and xenografting bovine SCO into the lateral ventricle of rats. Xenografts were either fresh bovine SCO or explants cultured for 30 days before transplantation. The grafts were investigated by electron microscopy and immunocytochemistry using antibodies against RF glycoproteins, serotonin and the glucose transporter I. Maximal time of transplantation was 43 days for isografts and 14 days for xenografts. The isografts were not reinnervated but were revascularized; they secreted into the ventricle RF glycoproteins that became progressively packed into pre-RF and RF structures identical to those formed by the SCO in situ. RF was confined to the host ventricle and at its distal end the constituent proteins disassembled. Xenografts were neither reinnervated nor revascularized and secreted into the host ventricle a material that never formed an RF. These findings indicate that the CSF factor responsible for the formation of RF is species specific, and that this process does not depend on the hydrodynamics of the CSF. The blood vessels revascularizing the isografted SCO acquired the characteristics of the vessels irrigating the SCO in situ, namely, a tight endothelium displaying glucose transporter I, and a perivascular space containing long-spacing collagen, thus indicating that basal release of glycoproteins may also occur in the grafted SCO.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 84
    ISSN: 1432-0878
    Keywords: Key words Axonal transport ; Purkinje cell ; Organotypic culture ; Microinjection ; Antimitotic drugs ; Cytoskeleton ; Dendritic transport ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Axonal and dendritic transport in single Purkinje neurons of cerebellar slice cultures was quantified as single transport distances. Examination of the cells within a vital tissue was regarded as being an approach to the in situ condition. The Purkinje cells were organotypically integrated in the in vitro tissues and extended long axonal projections connecting synapses to the target neurons. The tracer horseradish peroxidase (HRP) was applied via microinjection to the somata of the Purkinje cells and the injected neurons were incubated thereafter for defined time-intervals. The tracer was transported anterogradely into the neuron processes. The measurements on both the axonal and the dendritic transport of microinjected HRP revealed continuous transportation with increasing times of postincubation. This transport was reduced by the use of microtubule-depolymerizing drugs. The axonal transport of the tracer was either retarded in colchicine-treated cells or continuously reduced for up to 50% in vinblastine-treated neurons. Thus, a correlation of axonal transport to the microtubules was demonstrated. The dendrites were filled with the tracer after 60 min of postincubation. Dendritic transport was reduced by the use of vinblastine, and not significantly by colchicine. The results strongly support the dependence of neuronal transport on microtubules as a component of the cytoskeleton.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 85
    ISSN: 1432-0878
    Keywords: Key words Neurofilament ; Basket cell ; Pinceau ; Golgi apparatus ; Calcium binding protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract NCS-1 (neuronal calcium sensor) is a recently characterized member of a highly conserved neuron-specific family of calcium-binding proteins, which also includes frequenin and recoverin. The cellular and subcellular distributions of NCS-1 in the rat nervous system were investigated using light- and electron-microscopic immunohistochemistry. NCS-1 immunoreactivity was localized to neuronal cell bodies and axons throughout the brain and spinal cord but not to glial cells. The most intense labeling was observed in myelinated axons, the axonal ramifications of the basket cell in the cerebellar cortex, and large neurons in the brainstem and pons. These same structures were also characterized by heavy labeling for neurofilament protein, as determined by double-labeling experiments. Most axon terminals were unlabeled or only lightly labeled. The most remarkable subcellular staining occurred in the perikarya where intense labeling was associated with the membranes of the trans saccules of the Golgi apparatus. The widespread distribution of NCS-1 indicates that it may be active in a variety of calcium-dependent neuronal functions, whereas the specific subcellular localization to the Golgi apparatus and neurofilament-rich structures suggests a specialized role in calcium regulated protein trafficking and cytoskeletal interactions.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 86
    ISSN: 1432-0878
    Keywords: Key words Glial cell line-derived neurotrophic factor ; GDNF ; Ret ; GDNFR-α ; Brain-derived neurotrophic factor ; BDNF ; NT-3 ; NT-4 ; trk receptors ; Thyroid tissue ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-α) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expressed in the thyroid tissue. Therefore, it is unlikely that these factors serve a direct local autocrine or paracrine function in thyroid cell types, and a target-derived mode of action on neurons innervating the thyroid tissue is suggested. An opposite result has been found for the neurotrophic factor GDNF: thyroid tissue showed a high level of transcripts for the GDNF receptor subunits (GDNFR-α and Ret), while GDNF mRNA was undetectable. The in situ hybridization analysis of GDNFR-α and ret mRNA revealed an interesting difference in the cell distribution of these transcripts: ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces, while GDNFR-α expression is more homogeneous and widespread, including the more abundant cell type of the thyroid gland: the follicular cell. Double-labeling in situ hybridization/immunocytochemistry experiments, with a specific marker (calcitonin), showed that parafollicular cells express ret but not GDNFR-α. This differential distribution of the GDNF receptor components (GDNFR-α and ret) may reflect a peculiar biological role in intercellular communication in the thyroid gland.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 87
    ISSN: 1432-0878
    Keywords: Key words Water channel protein ; Aquaporin ; AQP5 ; Rat ; Salivary glands ; Immunolocalization ; Secretory stimulation ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Aquaporin-5 (AQP5) is a water channel protein and is considered to play an important role in water movement across the plasma membrane. We raised anti-AQP5 antibody and examined the localization of AQP5 protein in rat salivary and lacrimal glands by immunofluorescence microscopy. AQP5 was found in secretory acinar cells of submandibular, parotid, and sublingual glands, where it was restricted to apical membranes including intercellular secretory canaliculi. In the submandibular gland, abundant AQP5 was also found additionally at the apical membrane of intercalated duct cells. Upon stimulation by isoproterenol, apical staining for AQP5 in parotid acinar cells tended to appear as clusters of dots. These results suggest that AQP5 is one of the candidate molecules responsible for the water movement in the salivary glands.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 88
    ISSN: 1617-4623
    Keywords: Key words Molybdenum cofactor biosynthesis ; Drosophila ; cinnamon ; cnx1 ; GEPHYRIN
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Molybdoenzymes are involved in a variety of essential pathways including nitrate assimilation, sulfur and/or purine metabolism and abscisic acid biosynthesis. Most organisms produce several such enzymes requiring a molybdopterin cofactor for catalytic function. Mutations that result in a lack of the molybdopterin cofactor display a pleiotropic loss of molybdoenzyme activities, and this phenotype has been used to identify genes involved in cofactor biosynthesis or utilization. Although several cofactor genes have been analyzed in prokaryotes, much less is known concerning eukaryotic molybdenum cofactor (MoCF) genes. This work is focused on the Drosophila MoCF gene cinnamon (cin) which encodes a multidomain protein, CIN, that shows significant similarity to three proteins encoded by separate prokaryotic MoCF genes. These domains are also present in the product of cnx1, an Arabidopsis MoCF gene, and in GEPHYRIN, a rat protein thought to organize the glycine receptor, GlyR, within the postsynaptic membrane. Since this apparent consolidation of separate prokaryotic genes into a single eukaryotic gene is a feature of other conserved metabolic pathways, we wished to determine whether the protein's function is also conserved. This report shows that the plant gene cnx1 can rescue both enzymatic and physiological defects of Drosophila carrying cin mutations, indicating that the two genes serve similar or identical functions. In addition, we have investigated the relationship between CINNAMON and GEPHYRIN, using immunohistochemical methods to localize the CIN protein in Drosophila embryos. Most of the CIN protein, like GEPHYRIN in the rat CNS, is localized to the cell borders and shows a tissue-specific pattern of expression. In a parallel study, antibody to GEPHYRIN revealed the same tissue-specific expression pattern in fly embryos. Both antibodies show altered staining patterns in cin mutants. Taken together, these results suggest that GEPHYRIN may also carry out a MoCF-related function.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 89
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 262 (1999), S. 618-622 
    ISSN: 1617-4623
    Keywords: Key words Telomeric retrotransposons ; HeT-A elements ; Centric heterochromatin ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We have isolated two yeast artificial chromosome (YAC) clones from Drosophila melanogaster that contain a small amount of dodeca satellite (a satellite DNA located in the centromeric region of chromosome 3) and sequences homologous to the telomeric retrotransposon HeT-A. Using these YACs as probes for fluorescence in situ hybridization to mitotic chromosomes, we have localized these HeT-A elements to the centric heterochromatin of chromosome 3, at region h55. The possible origin of these telomeric elements in a centromeric position is discussed.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 90
    ISSN: 1573-0646
    Keywords: pharmacokinetics ; capecitabine ; 5-fluorouracil ; phase I trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract An excretion balance and pharmacokinetic study was conducted in cancer patients with solid tumors who received a single oral dose of capecitabine of 2000 mg including 50 μ Ci of 14C-radiolabelled capecitabine. Blood, urine and fecal samples were collected until radioactive counts had fallen to below 50 dpm/mL in urine, and levels of intact drug and its metabolites were measured in plasma and urine by LC/MS-MS (mass spectrometry) and 19F-NMR (nuclear magnetic resonance) respectively. Based on the results of the 6 eligible patients enrolled, the dose was almost completely recovered in the urine (mean 95.5%, range 86–104% based on radioactivity measurements) over a period of 7 days after drug administration. Of this, 84% (range 71–95) was recovered in the first 12 hours. Over this time period, 2.64% (0.69–7.0) was collected in the feces. Over a collection period of 24–48h, a total of 84.2% (range 80–95) was recovered in the urine as the sum of the parent drug and measured metabolites (5′-DFCR, 5′-DFUR, 5-FU, FUH2, FUPA, FBAL). Based on the radioactivity measurements of drug-related material, absorption is rapid (tmax 0.25–1.5 hours) followed by a rapid biphasic decline. The parent drug is rapidly converted to 5-FU, which is present in low levels due to the rapid metabolism to FBAL, which has the longest half-life. There is a good correlation between the levels of radioactivity in the plasma and the levels of intact drug and the metabolites, suggesting that these represent the most abundant metabolites of capecitabine. The absorption of capecitabine is rapid and almost complete. The excretion of the intact drug and its metabolites is rapid and almost exclusively in the urine.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 91
    ISSN: 1573-0646
    Keywords: docetaxel ; plasma assay ; clinical trials ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have developed a specific and sensitive method aiming atdocetaxel (Taxotere®) determination in plasma of treatedpatients. This involved solid-phase extraction of 1 ml of plasmaonto carboxylic acid (CBA) grafted silica cartridges followed byreversed-phase liquid chromatography with UV detection. The bestselectivity was obtained through the use of C18 Uptisphere® asstationary phase. The low limit of quantitation obtained (LOQ:5 ng/ml) allowed measurements of docetaxel up to 24 hours afterone-hour infusions with low dosages of drug (60 mg/m2). Themethod was applied successfully to monitor docetaxel plasma levelswithin two protocols associating fixed dosages of either methotrexate or gemcitabine with escalating doses of Taxotere®.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 92
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacodynamics ; effect compartment model ; indirect response ; sigmoid E max ; tiagabine ; GABA uptake inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pharmacological inhibition of GABA uptake transporters provides a mechanism for increasing GABAergic transmission, which may be useful in the treatment of various neurological disorders. The purpose of our investigations was to develop an integrated pharmacokinetic–pharmacodynamic (PK/PD) model for the characterization of the pharmacological effect of tiagabine, R-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl)nipecotic acid, in individual rats in vivo. The tiagabine-induced increase in the amplitude of the EEG 11.5–30 Hz frequency band (β), was used as pharmacodynamic endpoint. Chronically instrumented male Wistar rats were randomly allocated to four groups which received an infusion of 3, 10, or 30 mg kg −1 $$(\bar x \pm SE,{\text{ }}n = 23)$$ $$96 \pm 9$$ ml min -1 kg−1, 1.5ŷ0.1 L kg−1 and 20ŷ0.2 min.A time delay was observed between the occurrence of maximum plasma drug concentrations and maximal response. A physiological PK/PD model has been used to account for this time delay, in which a biophase was postulated to account for tiagabine available to the GABA uptake carriers in the synaptic cleft and the increase in EEG effect was considered an indirect response due to inhibition of GABA uptake carriers. The population values for the pharmacodynamic parameters characterizing the delay in pharmacological response relative to plasma concentrations were keo=0.030 min −1 and kout=81 min−1, respectively. Because of the large difference in these values the PK/PD model was simplified to the effect compartment model. Population estimates $$(\bar x \pm SE)$$ were E0=155 ŷ 6 μV, Emax=100 ŷ 5 μV, EC50=287 ŷ 7 ng ml−1, Hill factor=1.8 ŷ 0.2 and keo=0.030 ŷ 0.002 min −1. The results of this analysis show that for tiagabine the combined “effect compartment-indirect response” model can be simplified to the classical “effect compartment” model.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 93
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 491-512 
    ISSN: 1573-8744
    Keywords: muscle relaxants ; peripheral elimination ; pharmacokinetics ; peripheral concentrations ; volume of distribution ; pharmacokinetic model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract For anesthetic drugs undergoing nonorgan-based elimination, there is a definite trend towards using pharmacokinetic (PK) models in which elimination can occur from both central (k10 ) and peripheral compartments(k20 ). As the latter cannot be assessed directly, assumptions have to be made regarding its value. The primary purpose of this paper is to evaluate the impact of assuming various degrees of peripheral elimination on the estimation of PK parameters. For doing so, an explanatory model is presented where previously published data from our laboratory on three muscle relaxants, i.e., atracurium, doxacurium, and mivacurium, are used for simulations. The mathematical aspects for this explanatory model as well as for two specific applications are detailed. Our simulations show that muscle relaxants having a short elimination half-life are more affected by the presence of peripheral elimination as their distribution phase occupies the major proportion of their total area under the curve. Changes in the exit site dependent PK parameters (Vdss ) are also mostly significant when k20 is smaller than k10 . Although the physiological processes that determine drug distribution and those affecting peripheral elimination are independent, the two are mathematically tied together in the two-compartment model with both central and peripheral elimination. It follows that, as greater importance is given to k20 , the rate of transfer from the central compartment (k12 ) increases. However, as a result of a proportional increase in the volume of the peripheral compartment, peripheral concentrations remain unchanged whether or not peripheral elimination is assumed. These findings point out the limitations of compartmental analysis when peripheral elimination cannot be measured directly.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 94
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 27 (1999), S. 325-328 
    ISSN: 1573-8744
    Keywords: anesthetic techniques ; continuous infusion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We have previously described a method of rapidly obtaining a specified steady-state plasma concentration of an intravenous drug within precise limits. However the method is limited to drugs whose disposition may be characterized by an open two-compartment system. In this paper, we illustrate how the method can be extended to drugs whose disposition may be characterized by a mammillary model with any number of compartments. Refinements of our previous technique are also described.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 95
    ISSN: 1573-8744
    Keywords: psoriasis ; hu1124 ; CD11a ; CD3-positive lymphocytes ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of hu1124, a human anti-CD11a antibody, were investigated in human subjects with psoriasis. CD11a is a subunit of LFA-1, a cell surface molecule involved in T cell mediated immune responses. Subjects received a single dose of 0.03, 0.1, 0.3, 0.6, 1, 2, 3, or 10 mg/kg of hu1124 intravenously over 1–3 hr. Blood samples were collected at selected times from 60 min to 72 days after administration. Plasma samples were assayed for hu1124 by ELISA, and pharmacokinetic analyses were performed on the drug plasma concentrations. As the dose of hu1124 was increased, the clearance decreased from 322 ml/day per kg at 0.1 mg/kg to 6.6 ml/day per kg at 10 mg/kg of hu1124. The plasma hu1124 concentration–time profile suggested that the clearance of hu1124 was saturable above 10 μg/ml. In addition, treatment with hu1124 caused a rapid reduction in the level of CD11a expression on CD3-positive lymphocytes (T cells) to about 25% of pretreatment levels. Regardless of the hu1124 dose administered, cell surface CD11a remained at this reduced level as long as hu1124 was detectable (〉0.025 μg/ml) in the plasma. When hu1124 levels fell below 3 μg/ml, the drug was rapidly cleared from the circulation and expression of CD11a returned to normal within 7–10 days thereafter. In vitro, half-maximal binding of hu1124 to lymphocytes was achieved at about 0.1 μg/ml and saturation required more than 10 μg/ml. One of the receptor-mediated pharmacokinetic/pharmacodynamic models which was developed describes the dynamic interaction of hu1124 binding to CD11a, resulting in the removal of hu1124 from the circulation and reduction of cell surface CD11a. The model accounts for the continually changing number of CD11a molecules available for removing hu1124 from the circulation based on prior exposure of cells expressing CD11a to hu1124. In addition, the model also accounts for saturation of CD11a molecules by hu1124 at drug concentrations of approximately 10 μg/ml, thereby reducing the clearance rate of hu1124 with increasing dose.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 96
    ISSN: 1573-8744
    Keywords: drug–drug interactions ; NPML ; experimental design ; pharmacodynamic variability ; pharmacokinetics ; entropy ; covariate ; second stage model ; controlled trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Population approaches are appealing methods for detecting then assessing drug–drug interactions mainly because they can cope with sparse data and quantify the interindividual pharmacokinetic (PK) and pharmacodynamic (PD) variability. Unfortunately these methods sometime fail to detect interactions expected on biochemical and/or pharmacological basis and the reasons of these false negatives are somewhat unclear. The aim of this paper is firstly to propose a strategy to detect and assess PD drug–drug interactions when performing the analysis with a nonparametric population approach, then to evaluate the influence of some design variates (i.e., number of subjects, individual measurements) and of the PD interindividual variability level on the performances of the suggested strategy. Two interacting drugs A and B are considered, the drug B being supposed to exhibit by itself a pharmacological action of no interest in this work but increasing the A effect. Concentrations of A and B after concomitant administration are simulated as well as the effect under various combinations of design variates and PD variability levels in the context of a controlled trial. Replications of simulated data are then analyzed by the NPML method, the concentration of the drug B being included as a covariate. In a first step, no model relating the latter to each PD parameter is specified and the NPML results are then proceeded graphically, and also by examining the expected reductions of variance and entropy of the estimated PD parameter distribution provided by the covariate. In a further step, a simple second stage model suggested by the graphic approach is introduced, the fixed effect and its associated variance are estimated and a statistical test is then performed to compare this fixed effect to a given value. The performances of our strategy are also compared to those of a non-population-based approach method commonly used for detecting interactions. Our results illustrate the relevance of our strategy in a case where the concentration of one of the two drugs can be included as a covariate and show that an existing interaction can be detected more often than with a usual approach. The prominent role of the interindividual PD variability level and of the two controlled factors is also shown.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 97
    Electronic Resource
    Electronic Resource
    Springer
    Apoptosis 4 (1999), S. 239-243 
    ISSN: 1573-675X
    Keywords: Apoptosis ; cell survival ; differentiation ; Drosophila ; EGFR ; hid ; ras.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The Drosophila epidermal growth factor receptor (EGFR), functioning through the Ras/Raf/MAPK pathway, promotes cell proliferation and differentiation. Recent work has demonstrated that EGFR functions via the same Ras/Raf/MAPK pathway to promote cell survival. This review summarizes the role of EGFR in differentiation and survival during Drosophila eye development.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 98
    ISSN: 1573-6857
    Keywords: P element ; repressor ; maternal effect ; Drosophila ; population
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract As part of our effort to monitor changes in the clinal pattern of P element-associated traits in eastern Australian Drosophila melanogaster, we investigated the genomic P elements of 293 isofemale lines collected in the period 1991–1994 from 45 localities. P elements were present in many copies in all genomes examined, with full-size P and KP element size classes accounting for the large majority. SR elements were not present in at least 92% of the lines tested. South of about 26° south Latitude (°SLat), the ratio of KP to full-size P elements (KP/P ratio) increased, correlating weakly with the P-M phenotypes of the populations, from moderately P populations (26–29°SLat) to M populations (37–38°SLat) North of 26°SLat, in weak P populations, the KP/P ratio was higher than between 26 and 29°Slat. The KP/P ratio appears to be higher in the northern populations than it was when previous studies were done. Overall, a high KP/P ratio among lines correlated roughly with a lack of P activity, but it also correlated with reduced repressor function. In a sample of 30 lines, a maternal effect of repressor function did not show a pattern with latitude, nor with KP/P ratio, nor with presence or absence of P activity.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 99
    Electronic Resource
    Electronic Resource
    Springer
    Genetica 105 (1999), S. 43-62 
    ISSN: 1573-6857
    Keywords: distribution ; Drosophila ; retrotransposon ; transposable element
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We present a global analysis of the distribution of 43 transposable elements (TEs) in 228 species of the Drosophila genus from our data and data from the literature. Data on chromosome localization come from in situ hybridization and presence/absence of the elements from southern analyses. This analysis shows great differences between TE distributions, even among closely related species. Some TEs are distributed according to the phylogeny of their host specie; others do not entirely follow the phylogeny, suggesting horizontal transfers. A higher number of insertion sites for most TEs in the genome of D. melanogaster is observed when compared with that in D. simulans. This suggests either intrinsic differences in genomic characteristics between the two species, or the influence of differing effective population sizes, although biases due to the use of TE probes coming mostly from D. melanogaster and to the way TEs are initially detected in species cannot be ruled out. Data on TEs more specific to the species under consideration are necessary for a better understanding of their distribution in organisms and populations.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 100
    ISSN: 1573-6857
    Keywords: Drosophila ; hobo ; hot spot ; integration specificity ; transposable elements
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We analyzed the integration specificity of the hobo transposable element of Drosophila melanogaster. Our results indicate that hobo is similar to other transposable elements in that it can integrate into a large number of sites, but that some sites are preferred over others, with a few sites acting as integration hot spots. A comparison of DNA sequences from 112 hobo integration sites identified a consensus sequence of NTNNNNAC, but this consensus was insufficient to account for the observed integration specificity. To begin to define the parameters affecting hobo integration preferences, we analyzed sequences flanking a donor hobo element, as well as sequences flanking a hobo integration hot spot for their relative influence on hobo integration specificity. We demonstrate experimentally that sequences flanking a hobo donor element do not influence subsequent integration site preference, whereas, sequences contained within 31 base pairs flanking an integration hot spot have a significant effect on the frequency of integration into that site. However, sequence analysis of the DNA flanking several hot spots failed to identify any common sequence motif shared by these sites. This lack of primary sequence information suggests that higher order DNA structural characteristics of the DNA and/or chromatin may influence integration site selection by the hobo element.
    Type of Medium: Electronic Resource
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...