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  • 1
    Electronic Resource
    Electronic Resource
    Carbonate sediment transport pathways based on foraminifera: case study from Frank Sound, Grand Cayman, British West Indies (1998)
    Oxford UK : Blackwell Science Ltd, UK
    Sedimentology 45 (1998), S. 0 
    Details
    ISSN: 1365-3091
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: Foraminifera can be used to determine the source(s) of carbonate sediment and the directions of sediment transport in shallow, coastal lagoons such as Frank Sound on the south-central coast of Grand Cayman. These determinations, based on the distribution of foraminiferal assemblages and ‘tracer species’ (numerically abundant species that live in known physiographic units and/or ecological conditions), show that the lagoonal sediments are a mixture of grains that originated in the lagoon and forereef. The variable proportions of these foraminifera throughout the lagoon reflects the dynamic processes that control lagoonal sedimentation. Amphistegina gibbosa, Discorbis rosea, and Asterigerina carinata lived in the forereef environment. The fact that these ‘tracer species’ are found throughout Frank Sound and in the beach sands, shows that they were transported across the reef crest and the lagoon. Abrasion-resistant Archaias angulatus, a‘tracer species’ indicative of a lagoonal setting, forms up to 50% of foraminiferal assemblages found in the lagoonal sediments. Preferential winnowing of small tests from these populations indicates sorting under high energy conditions. The vertical distribution of the forereef and lagoonal foraminifera in the sediment blanket that covers the floor of Frank Sound indicates that these processes are temporally persistent.Transportation of forereef foraminifera into and around the lagoon and sorting of the lagoonal foraminifera cannot take place under ‘normal’ conditions when the tranquil lagoon is characterized by weak currents. Storms and/or hurricanes, however, generate short-lived high-energy events that can move and sort the sediment and foraminifera. At the height of a storm, water and sediment are moved over the reef and then piled and held onshore by the onshore winds and the constant flow of water over the reef and across the lagoon. These currents can mix some of the lagoonal and forereef sediments. As a storm wanes, however, the ‘piled water’ flows offshore via strong rip currents that pass into the ocean through the channels which transect the reef. These currents winnow and/or strip sediment from the lagoon and may transport lagoonal sediments into the forereef area. As a result, residual lagoonal sediment is commonly characterized by larger and abrasion-resistant foraminifera.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3091.1998.00133.x
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  • 2
    Electronic Resource
    Electronic Resource
    Stereoselective pharmacokinetics of ifosfamide and its 2- and 3-N-dechloroethylated metabolites in female cancer patients (1996)
    Springer
    Cancer chemotherapy and pharmacology 37 (1996), S. 451-456 
    Details
    ISSN: 1432-0843
    Keywords: Key words Ifosfamide enantiomers ; N-Dechloroethylation ; Metabolism ; Enantioselective pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The pharmacokinetics of the R and S enantiomers of ifosfamide (IFF) and of its 2- and 3-N-dechloroethylated metabolites (2-DCE-IFF and 3-DCE-IFF) were investigated in 14 cancer patients treated with a 3-h infusion of (R,S)-IFF (3 g/m2) with mesna uroprotection. An enantioselective gas chromatographic-mass spectrometric (GC-MS) assay was used to determine the concentrations in plasma and urine. The AUCs of (R)-IFF were significantly larger than those of (S)-IFF (2480±200 vs 1960±150 μM . h). The terminal half-lives (7.57±0.99 h) and mean residence times (11.17±1.10 h) of (R)-IFF were significantly longer than those of (S)-IFF, 6.03±0.82 h and 9.37±0.88 h, respectively. The mean volume of distribution at steady state of (R)-IFF (25.68±0.80 l/m2) was slightly smaller than that of (S)-IFF (27.35±0.89 l/m2). While the renal clearances of (R)-IFF and (S)-IFF were similar, the nonrenal clearance was significantly lower for (R)-IFF (30.20±2.70 vs 41.40±3.55 ml/m2 per min) as was total clearance (41.52±2.90 vs 52.37±3.75 ml/m2 per min). The AUC values for all of the DCE metabolites from (S)-IFF were significantly greater than those from (R)-IFF with 47% of the measured AUC accounted for by DCE from (S)-IFF compared to only 20% for (R)-IFF. Therefore, the enantioselective difference in IFF elimination can be partially explained by differences in N-dechloroethylation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050411
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  • 3
    Electronic Resource
    Electronic Resource
    Flavone acetic acid (LM 975, NSC 347512) A novel antitumor agent (1987)
    Springer
    Cancer chemotherapy and pharmacology 19 (1987), S. 6-10 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Flavone acetic acid (FAA) is a synthetic flavonoid compound which has recently begun clinical trials as an antitumor agent based on its striking activity in solid tumor model systems. The pharmacologic behavior of FAA in animals appears to be predictive of both its cytotoxic efficacy and its toxicity to normal tissues (principally the central nervous system and gastrointestinal tract). The design and conduct of phase I studies in man are based upon these principles, with the goal of maximizing their safety and efficacy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296246
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  • 4
    Electronic Resource
    Electronic Resource
    A strategy for the development of two clinically active cisplatin analogs: CBDCA and CHIP (1990)
    Springer
    Cancer chemotherapy and pharmacology 25 (1990), S. 395-404 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The antitumor agent cisplatin has a broad antitumor spectrum and has been incorporated into regimens that are curative for some malignant diseases. However, one of the major limitations to its clinical usefulness is the incidence of severe toxicities involving several major organ systems. Therefore, much enthusiasm has been generated for the development of cisplatin analogs that demonstrate an improved therapeutic index in some preclinical models. The two most promising analogs are CBDCA (carboplatin) and CHIP (iproplatin). The preclinical and early clinical trial results have demonstrated that these two compounds show activity in cisplatin-responsive tumors. The preclinical background providing the rationale for the clinical development of these two analogs is described. We suggest a means of screening for each analog's clinical antitumor activity and determining the analogs' utility against specific malignant diseases compared with that of the parent compound or standard treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686049
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  • 5
    Electronic Resource
    Electronic Resource
    Anthracycline analogs The past, present, and future (1986)
    Springer
    Cancer chemotherapy and pharmacology 18 (1986), S. 185-197 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273384
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  • 6
    Electronic Resource
    Electronic Resource
    Letter to the editors (1987)
    Springer
    Cancer chemotherapy and pharmacology 19 (1987), S. 350-350 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00261488
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  • 7
    Electronic Resource
    Electronic Resource
    Comparative studies between the effects of mitozolomide and two novel tetrazepinones PYRCL and QUINCL on NIH:OVCAR-3 cells (1998)
    Springer
    Cancer chemotherapy and pharmacology 42 (1998), S. 59-67 
    Details
    ISSN: 1432-0843
    Keywords: Key words Tetrazepinones ; Cell cycle arrest ; DNA damage ; OVCAR-3 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytotoxicity, reduction of macromolecule synthesis and cell cycle perturbations by two novel 3-(2-chloroethyl)-tetrazepinones, PYRCL and QUINCL were compared with those produced by the structurally related 3-(2-chloroethyl)-tetrazinone, mitozolomide, in the OVCAR-3 cell line. Methods: Macromolecule synthesis was determined by incorporation of 3H-thymidine, 3H-uridine and 3H-leucine into acid-precipitable fractions of OVCAR-3 cell extracts. Maxam-Gilbert sequencing was used to compare the DNA alkylating sites induced by the tetrazepinones, with those created by mitozolomide. Alkaline sucrose-density sedimentation was employed to detect genomic DNA damage. Also, the effects of the tetrazepinones on the cell cycle were determined by univariate flow cytometry. Results: At 3 h post-treatment, mitozolomide appeared as a selective inhibitor of DNA synthesis, while both tetrazepinones inhibited the synthesis of all three macromolecules. At 24 h post-treatment, the inhibition of DNA synthesis was observed to increase in cells treated with mitozolomide, while it decreased in those previously exposed to the tetrazepinones. Also at 24 h post-treatment, mitozolomide induced accumulation of cells in S(late)/G2M at low concentrations and in S-middle at high concentrations. In contrast, at the same recovery time, cells treated with the tetrazepinones accumulated specifically in G2M, the strength of the block being dose-dependent. At an equimolar concentration, the tetrazepinones induced weaker guanine N-7 alkylation than mitozolomide. By 24 h after treatment, cells exposed to the tetrazepinones showed significantly greater DNA fragmentation than those previously treated with mitozolomide. Conclusion: In summary, based on (a) their effects on DNA, RNA, protein synthesis and on the cell cycle, (b) their alkylating power and (c) their interactions with DNA, the 3-(2-chloroethyl)tetrazepinones appeared to kill tumor cells by a novel mechanism which may significantly differ from that of their 3-(2-chloroethyl)-tetrazinone counterpart, mitozolomide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050785
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  • 8
    Electronic Resource
    Electronic Resource
    Evidence that the amygdala is involved in the disinhibitory effects of 5-HT3 receptor antagonists (1991)
    Springer
    Psychopharmacology 104 (1991), S. 545-551 
    Details
    ISSN: 1432-2072
    Keywords: 5-HT3 receptors ; Amygdala ; Dorsal raphe nucleus ; Ondansetron ; Granisetron ; Social interaction ; Water-lick conflict test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of various 5-HT3 receptor antagonists were examined in the social interaction (SI) test following discrete microinjection into either the dorsal raphe nucleus (DRN) or amygdala of the rat. Following DRN injection, ondansetron, ICS205-930, and MDL72222 (5–500 ng) all failed to modify SI under high light/unfamiliar (HLU) test conditions relative to vehicle pretreated controls. The 5-HT3 receptor agonist, 2-Me 5-HT (100–2500 ng), was similarly ineffective under both HLU and low light/familiar (LLF) conditions, although 5-HT (20–100 ng) increased SI under the HLU paradigm. After amygdaloid injection, ondansetron (10–100 ng), granisetron (1–10 ng), ICS205-930 (10–100 ng), GR 65630 (1–10 ng), and MDL72222 (100–1000 ng) all significantly increased SI under the HLU but not LLF condition. Furthermore, a detailed behavioural analysis revealed that the behaviours underlying this increase were similar to those seen in vehicle pretreated animals tested in the LLF compared to HLU condition. The benzodiazepine, flurazepam (200 ng), increased both SI (HLU condition) and punished responding in a modified water-lick conflict model, after amygdaloid injection. Both ondansetron (10–1000 ng) and ICS205-930 (1–100 ng) were ineffective in the conflict test. Finally, 2-Me 5-HT and 5-HT (100–10 000 ng) reduced SI under the LLF test condition with no concomitant change in locomotor activity. It is concluded that the amygdala, but not the DRN, may represent an important neuroanatomical locus for the disinhibitory, perhaps anxiolytic, properties of 5-HT3 receptor antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245664
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  • 9
    Electronic Resource
    Electronic Resource
    Improved Screening of cDNAs Generated by mRNA Differential Display Enables the Selection of True Positives and the Isolation of Weakly Expressed Messages (1997)
    Springer
    Plant molecular biology reporter 15 (1997), S. 236-245 
    Details
    ISSN: 1572-9818
    Keywords: Differential display ; Lycopersicon esculentum ; Ethylene-responsive ; Low abundance mRNAs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The high percentage of false positives generated by differential display (as high as 85%) has previously limited the potential of the method. This report describes an efficient methodology that enables false positives to be discarded prior to cloning, via reverse Northern analysis. This first step of the screening also allows the detection of putative low abundance differential clones. Following cloning, a second reverse Northern combined with partial DNA sequencing and RT-PCR detection allows isolation of all differential cDNAs including very low abundance clones. Use of the sequential screening procedure described here led to the isolation of novel tomato genes responding to the plant hormone ethylene while minimising labor and materials input.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007482318668
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  • 10
    Electronic Resource
    Electronic Resource
    First-Pass Effect of cis-3,4-Dichloro-N-methyl-N-(2-(l-pyrrolidinyl)-cyclohexyl)-benzamide (U-54494) in Rats— A Model with Multiple Cannulas for Investigation of Gastrointestinal and Hepatic Metabolism (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 1524-1529 
    Details
    ISSN: 1573-904X
    Keywords: multiple administration routes ; rat cannulation ; metabolism ; liver ; gut
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A multiple cannulated rat model was utilized to investigate the relative contribution of the gut and liver as sites of first-pass metabolism of orally administered U-54494 A, an anticonvulsant drug candidate. Each rat received a dose of U-54494 A by oral, intraportal, and intravenous routes on three separate occasions. Intraportal and intravenous doses were administered through chronic cannulas surgically implanted in the portal vein and superior vena cava, respectively. Blood samples were collected over a 6-hr period from the superior vena cava cannula. The mean (n = 3) bioavailability of orally dosed U-54494A was 4.5 ± 1.1%, while that dosed intraportally was 19.1 ± 3.0%. The relative contribution of the gut and liver as sites of first-pass extraction and/or metabolism of orally administered drug was 69.9 ± 14.0% and 24.5 ± 12.2%, respectively. Approximately 35 to 40% of the total plasma clearance was attributed to the liver. The plasma concentrations of the four known metabolites of U-54494A were apparently higher for the oral and intraportal routes compared to that after intravenous administration. This investigation confirms that the low oral bioavailability of U-54494A in the rat can be primarily attributed to both extensive intestinal and hepatic first-pass metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018985015596
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