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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 639 (1991), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Industrial & engineering chemistry research 31 (1992), S. 164-171 
    ISSN: 1520-5045
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 83 (1985), S. 6457-6466 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: We present a general theory of equilibrium polymerization in a binary mixture by applying the n-vector model for magnetism in a weak field. Results are given for the temperature dependence of the order parameters, polymer length, and phase diagrams in the concentration–temperature plane. In addition to phase separations between two monomer phases and between a monomer and a polymer phase, the phase diagrams show the possibility of coexistence between two polymer phases with a critical point. It is shown that our theory becomes identical to the earlier theory for equilibrium copolymerization of Tobolsky and Owen when the molecular field approximation and some additional approximations are used.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0843
    Keywords: Key words: Etoposide – Topoisomerase II – Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A number of clinically important drugs such as the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26), the anthracyclines daunorubicin and doxorubicin (Adriamycin), and the aminoacridine amsacrine exert their cytotoxic action by stabilizing the cleavable complex formed between DNA and the nuclear enzyme topoisomerase II. We have previously demonstrated in several in vitro assays that the anthracycline aclarubicin (aclacinomycin A) inhibits cleavable-complex formation and thus antagonizes the action of drugs such as VP-16 and daunorubicin. The present study was performed to validate these in vitro data in an in vivo model. At nontoxic doses of 6 and 9 mg/kg, aclarubicin yielded a marked increase in the survival of non-tumor-bearing mice given high doses of VP-16 (80 – 90 mg/kg) in six separate experiments. In therapy experiments on mice inoculated with Ehrlich ascites tumor cells, aclarubicin given at 6 mg/kg roughly halved the increase in median life span induced by VP-16 at doses ranging from 22 to 33 mg/kg. An attempt to determine a more favorable combination of VP-16 and aclarubicin by increasing VP-16 doses failed, as the two drugs were always less effective than VP-16 alone. The way in which VP-16-induced DNA strand breaks lead to cell death remains unknown. However, VP-16 has been reported to cause apoptosis (programmed cell death) in several cell lines. To ascertain whether the protection given by aclarubicin could have a disruptive effect on the apoptotic process, we used the small intestine as an in vivo model. Whereas VP-16-induced apoptosis in crypt stem cells was detectable at a dose as low as 1.25 mg/kg, aclarubicin given at up to 20 mg/kg did not cause apoptosis. Indeed, aclarubicin caused a statistically significant reduction in the number of cells rendered apoptotic by VP-16. The present study thus confirms the previous in vitro experiments and indicates the value of including an in vivo model in a preclinical evaluation of drug combinations.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-0743
    Keywords: transesophageal echocardiography ; infective endocarditis ; spontaneous echo contrast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infective endocarditis is associated with significant morbidity and mortality. Valvular destruction and congestive heart failure are more common in patients with echocardiographically detectable vegetations. In addition, spontaneous platelet aggregation is increased when vegetations are present on cardiac valves. The aim of the study was to assess the prognostic value of spontaneous echo contrast (SEC) imaging, as SEC is supposed to reflect red blood cell aggregates stimulated by platelet activity. We studied 293 patients with clinical signs of infective endocarditis. Vegetations, attached to the aortic or mitral valve, were found in 130 patients (44.4%) who were followed for a mean period of 12 months. In 34 of these 130 patients (26.2%) SEC was imaged during the initial transesophageal echocardiographic examination. In these patients SEC indicated a prolonged healing of infective endocarditis with a specificity of 91.2%, a sensitivity of 77.3%, a positive accuracy of 77.3%, a negative accuracy of 74.3%. Multivariate analysis revealed that SEC is a risk factor for valve replacement (p 〈 0.001) and for embolic events (p 〈 0.001), less for mortality (p 〈 0.01), and lowest for abscess formation (p 〈 0.05). The dose of ADP to induce half-maximal platelet aggregation was significantly lower in patients with SEC (0.71 ± 0.15μl) than without SEC (1.05 ± 0.12μl;p 〈 0.05), implying an increased spontaneous platelet aggregation in the presence of SEC. Our data provide evidence that systemically activated coagulation plays an important role in infective endocarditis. SEC, the echocardiographic implication of an increased platelet aggregation, predicts complications such as thromboembolic events and the need for surgery and is closely related to the prolonged healing period of infective endocarditis. In addition to demonstrating vegetations, transesophageal echocardiography provides information helpful in assigning patients to a high-risk subgroup. Transesophageal echocardiography may play an important role in assessing the clinical outcome of these patients.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The catalytic domain of PAC1 (amino acids 127-314; cPACl) was expressed as a soluble glutathione S-transferase (GST) fusion protein, and the enzymatic activity of the highly purified GST-cPACl was assayed using a variety of substrates. In a screen of potential physiological substrates, we used ...
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  • 7
    ISSN: 1432-0509
    Keywords: Esophagus, motility disorder ; Manometry ; Radiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Radiography and manometry of the esophagus were compared in 77 patients consecutively referred for manometric investigation on suspicion of esophageal motility disorder. Radiography and manometry were carried out simultaneously, and the results were assessed blindly. The examination comprised barium swallow, bread barium swallow, and barium swilling. Considering manometry as the standard, the overall sensitivity and specificity of the radiologic examinations were 90.4% and 92.0%, respectively. We conclude that radiology is an excellent investigation for the separation of patients with and without esophageal motility disorders, but correct subclassification often required manometry.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 30 (1992), S. 219-220 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent studies by Boesch et al. have demonstrated that a nonimmunosuppressive cyclosporin analog, SDZ PSC 833 (an analog of cyclosporin D), is an active multidrug-resistance modifier that is at least 10 times more potent than cyclosporin A. In vitro accumulation and cytotoxicity experiments using daunorubicin (DNR) and vincristine (VCR) under the influence of SDZ PSC 833 and cyclosporin A were performed in wild-type (EHR2) and the corresponding highly DNR-resistant (about 80-fold) Ehrlich ascites tumor cells (EHR2/DNR+). In accumulation experiments, both SDZ PSC 833 and cyclosporin A were found to reverse the multidrug-resistant (MDR) phenotype, but to the same degree at equimolar concentrations. Thus, in EHR2/DNR+ cells, both cyclosporins at 5 μg/ml enhanced DNR and VCR accumulation to sensitive levels, but only a negligible effect on DNR accumulation in the drug-sensitive cells was seen. In the clonogenic assay, the cytotoxicity of the two modulators was equal. The lethal dose for 50% of the cell population (LD50) was approx. 7 μg/ml for both compounds, and no toxicity was observed at concentrations below 2 μg/ml. At nontoxic doses, both cyclosporins effectively increased the cytotoxicity of DNR and VCR in a concentration-dependent manner. The dose-response curves were nearly identical and did not demonstrate differences in modulator potency. These data permit the conclusion that cyclosporin A and SDZ PSC 833 do raise the intracellular accumulation of DNR and VCR to the same levels and that SDZPSC 833 does not potentiate cytotoxicity better than cyclosporin A in EHR2/DNR+ cells. However, since the new compound is nonimmunosuppressive and causes less organ toxicity, clinical studies of its MDR modulating effect seem highly relevant.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The epipodophyllotoxines VP-16 and VM-26 are chemically closely related. VM-26 has been found to be considerably more potent than VP-16 in vitro in a number of investigations. Although the drugs have been known for 〉20 years, they have not been compared at clearly defined equitoxic doses on an optimal schedule in vivo and it has not been clarified as to whether a therapeutic difference exists between them. A prolonged schedule is optimal for both drugs; accordingly we determined the toxicity in mice using a 5-day schedule. The dose killing 10% of the mice (LD10) was 9.4 mg/kg daily (95% confidence limits, 7.4–11.8) for VP-16 and 3.4 (2.5–4.5) mg/kg daily for VM-26. In vitro, we found VM-26 to be 6–10 times more potent than VP-16 in a clonogenic assay on murine tumors P388 and L1210 leukemia and Ehrlich ascites. This pattern was also demonstrated in a multidrug-resistant subline of Ehrlich selected for resistance to daunorubicin (Ehrlich/DNR+), as it was 30 times less sensitive than Ehrlich cells to both VP-16 and VM-26. Using 90%, 45%, and 22% of the LD10 on the same murine tumors in vivo, we found that the effect of the two drugs was equal as evaluated by both the increase in life span and the number of cures. The drugs were also compared in nude mice inoculated with human small-cell lung cancer lines OC-TOL and CPH-SCCL-123; however, they were more toxic to the nude mice and only a limited therapeutic effect was observed. In conclusion, the complete cross-resistance between the two drugs suggests that they have an identical antineoplastic spectrum. VM-26 was more potent than VP-16 in vitro; however, this was not correlated to a therapeutic advantage for VM-26 over VP-16 in vivo
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