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  • 11
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Theoretical Biology 127 (1987), S. 381-391 
    ISSN: 0022-5193
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Theoretical Biology 150 (1991), S. 175-191 
    ISSN: 0022-5193
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-0738
    Keywords: Oximes ; HLö 7 [CAS reg. No. 120 103-35-7] ; HI 6 [CAS reg. No. 34433-31-31] ; Obidoxime [CAS reg. No. 114-90-9] ; Syntheses ; Organophosphates ; Therapy ; Reactivation ; Acetylcholinesterase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HLö 7 dimethanesulfonate (1-[[[4-(aminocarbonyl)pyridinio] methoxy] methyl] -2,4-bis [(hydroxyimino) methyl]pyridinium dimethanesulfonate) is a broad-spectrum reactivator against highly toxic organophosphorus compounds. The compound was synthesized by a new route with the carcinogenic bis(chloromethyl)ether being substituted by the non-mutagenic bis(methylsulfonoxymethyl)ether. The very soluble dimethanesulfonate of obidoxime was also prepared by this way. HLö 7 dimethanesulfonate is the first water-soluble salt of HLö 7 that should be suitable for the wet/dry autoinjector technology, because aqueous solutions of HLö 7 are not very stable (calculated shelf-life 0.2 years when stored at 8°C, 1 M solution, pH 2.5). The crystalline preparation contains 96% of thesyn/syn-isomer, less than 2% of thesyn/anti-isomer and some minor identified by-products. HLö 7 was very efficient in reactivating acetylcholinesterase (AChE) blocked by organophosphates as long as ageing did not prevent dephosphylation. HLö 7 was superior to HI 6 (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyimino)methyl]pyridinium dichloride) in reactivating soman and sarin-inhibited AChE from erythrocytes, and literature data indicate that HLö 7 exceeds HI 6 by far in reactivating tabun-inhibited AChE. In atropine-protected, soman-poisoned mice HLö 7 was three times more potent than HI 6 (protective ratio 5 versus 2.5), and in sarin-poisoned mice HLö 7 was 10 times more potent than HI 6 (protective ratio 8 for both oximes). In atropine-protected guinea-pigs HLö 7 was less effective than HI 6 (protective ratio: 2.3 versus 5.2 for soman; 5.2 versus 6.8 for sarin; 4.3 versus 3.8 for tabun). The mean survival time of anaesthetized guinea-pigs exposed to 5 LD50 soman (6.3 min) was increased by atropine (27 min) and atropine + HLö 7 (57 min). HLö 7 alone did not prolong the survival. The most impressive effect of HLö 7 was on respiration: 3 min after i.v. injection of HLö 7 and atropine, the depressed respiration increased rapidly to 60% of control and remained at that level during the observation period (60 min). With atropine alone, respiration recovered only slowly. Behavioural and physiologic parameters were determined in atropine-protected mice exposed to a sublethal soman dose. The running performance was significantly improved by HLö 7. Even central symptoms, e.g. hypothermia and convulsions, were decreased markedly by HLö 7 (evaluation 60 min after poisoning). The pharmacokinetic data for HLö 7 in male beagle dogs are similar to those of HI 6. After i.v. injection: t1/2α = 5 min; t1/2ß = 46 min; VD = 0.24 1/kg; Clp1 = 3.7 ml x min−1 x kg−1; Clren= 3.2 ml x min−1 x kg−1; renal excretion of unchanged HLö 7 = 86%. After i. m. injection: t1/2abs = 14 min; t1/2ß = 48 min; Vd = 0.27 1/kg; Clp1= 3.9 ml x min−1 x kg−1; Clren= 2.7 ml x min−1 x kg−1; renal excretion of unchanged HLö 7 = 76%; bioavailability 〉95%. Plasma protein binding was 〈5%; HLö 7 did not permeate into red cells. A dose of 20 μmol/kg was well tolerated both after i.v. and i.m. administration. In anaesthetized dogs (chloralose) HLö 7 i.v. (20 (imol/kg) showed marginal hypotensive effects, whereas 50 μmol/kg resulted in decreased mean blood pressure (−15%) and blood flow (−30%) without reflex tachycardia. One out of four dogs developed a circulatory shock syndrome with anuria. Respiration varied only transiently. Blood gases and pH were not influenced. Similar cardiovascular effects were observed in anaesthetized (urethane) guinea-pigs. In isolated guinea-pig hearts (Langendorff) sinus and ventricular heart rate were not influenced by HLö 7 〈500 μM. HLö 7 antagonized both carbachol and nicotine effects. Red cell AChE was inhibited by HLö 7 by up to 50%; C50 about 100 μM. Previously, HLö 7 was shown to block ganglionic transmission (IC50= 500 μM), probably due to ion-channel blockade. These data indicate that HLö 7 combines ganglion blocking, anticholinergic and indirect cholinergic properties like other bispyridinium compounds. The results suggest that HLö 7 may be tolerated by man at a dose of 10 μmol/kg. Vital functions are not expected to be impaired. At such a dose (250–500 mg), which can be injected by an autoinjector, HLö 7 is expected to be superior to HI 6.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 95 (1979), S. 115-122 
    ISSN: 1432-1335
    Keywords: Acetat ; Anaerobiose ; Lipogenese ; Oktanoat ; Pyruvate ; Tritiiertes Wasser ; Tumor ; Acetate ; Anaerobiosis ; Lipogenesis ; Octanoate ; Pyruvate ; Tritiated water ; Tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Anaerobic culture conditions (95% argon/5% CO2) caused a slightly greater increase in total lipids of Ehrlich ascites tumor cells than a gas phase of 20% O2, 75% N2, 5% CO2. Whereas the rate of [U-14C]acetate incorporation into total lipids and lipid-subclasses rose markedly in the absence of oxygen, a drastic decrease of [U-14C]pyruvate and [1-14C]octanoate incorporation as well as a 30% reduction of 3H incorporation into lipids from tritiated water were observed under these conditions. Since profound changes in the metabolic state of cells cause alterations in the specific activity of the acetyl-CoA pool but do not alter the specific activity of intracellular water, this precursor is considered to be an adequate monitor for lipogenesis under aerobic and anaerobic culture conditions. Therefore, it is concluded that Ehrlich ascites tumor cells are not able to reoxidize NADH/NADPH in the absence of oxygen by a stimulation of biosynthesis of fatty acids as is discussed to be the case in normal cells. The slight increase in total lipids of anaerobically cultured cells seems to be the result of an imbalance between normal uptake and impaired utilization of lipids from serum-supplemented culture medium.
    Notes: Zusammenfassung Unter anaeroben Kulturbedingungen, (95% Argon 5% CO2) stieg der Gesamtlipidgehalt in Ehrlich Ascites Tumorzellen etwas stärker an als unter aeroben Bedingungen (20% O2, 75% N2, 5% CO2). In Abwesenheit von Sauerstoff war der Einbau von [U-14C]Acetat in die Gesamtlipidfraktion als auch in einzelne Lipidklassen, deutlich erhöht, wohingegen ein drastischer Abfall der Einbauraten aus [U-14C]Pyruvat und [1-14C]Oktanoat sowie eine signifikante Verminderung des Einbaus von 3H-Wasser unter diesen Kulturbedingungen beobachtet wurde. Da die spezifische Aktivität von intrazellulärem Wasser auch unter tiefgreifenden Änderungen des metabolischen Zustandes der Zellen praktisch konstant bleibt, wird 3H-Wasser als die zuverlässigste Vorstufe zur Messung der Lipidbiosynthese unter aeroben und anaeroben Kulturbedingungen angesehen. Aus den Ergebnissen wird geschlossen, daß Ehrlich Ascites Tumorzellen nicht, wie es für Normalgewebe angenommen wird, in der Lage sind, NADH/NADPH bei Ausschluß von Sauerstoff durch erhöhte Fettsäuresynthese zu, reoxidieren. Der beobachtete Anstieg im Gesamtlipidgehalt von anaerob kultivierten Zellen erklärt sich wahrscheinlich durch ein Ungleichgewicht zwischen normaler Aufnahme und gehemmtem Abbau von exogenen Lipiden.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 110 (1985), S. 11-16 
    ISSN: 1432-1335
    Keywords: Tumour growth ; Cell kinetics ; Melanoma ; Nude mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A human malignant melanoma was grown in nude mice. The tumour showed an exponential growth for several weeks which gradually slowed down, until following week 8 the tumour growth ceased. The reasons for this growth pattern were examined by labelling techniques (PLM, LI). The tumour cell production as quantified by the growth fraction, showed only a moderate reduction which, taken alone, could not explain the growth cessation. The important mechanism seems to be an increased loss of tumour cells during the intermitotic interval. While the loss of cells/h remains constant the total intermitotic cell loss is increased because the cell cycle times are prolonged by 50% from the exponential phase (45 h in week 3) to the plateau phase (66 h in week 8).
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 368 (1994), S. 831-834 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Each five-membered ring in the target polymer la (Fig. 1) is joined to three six-membered rings as shown. The polymer should, therefore, have a planar, board-like structure. There is no doubt that the well known and often applied method to increase the solubility of conformationally rigid polymers ...
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Applied physics 63 (1996), S. 511-516 
    ISSN: 1432-0649
    Keywords: PACS: 03.65.Bz; 84.40.Ik
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract.  We propose a phase-sensitive micromaser setup to demonstrate experimentally a violation of a Bell-type inequality. The interaction of atoms with the cavity field produces entanglement between the atoms and the cavity photons and therefore also between the atoms. We derive a Bell-type inequality for the atom–atom correlations and show that it can be violated not only in an idealized model but also under realistic circumstances when various sources of additional randomness are accounted for. Among them are the energy dissipation in the resonator and the Poissonian arrival statistics of the atoms.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Applied physics 63 (1996), S. 511-516 
    ISSN: 1432-0649
    Keywords: 03.65.Bz ; 84.40.1k
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We propose a phase-sensitive micromaser setup to demonstrate experimentally a violation of a Bell-type inequality. The interaction of atoms with the cavity field produces entanglement between the atoms and the cavity photons and therefore also between the atoms. We derive a Bell-type inequality for the atom-atom correlations and show that it can be violated not only in an idealized model but also under realistic circumstances when various sources of additional randomness are accounted for. Among them are the energy dissipation in the resonator and the Poissonian arrival statistics of the atoms.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 116 (1990), S. 106-108 
    ISSN: 1432-1335
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1432-0584
    Keywords: Hodgkin's lymphoma ; Clinical trial ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a national multicentre trial in the FRG patients with Hodgkin's lymphoma in stages CS/PS III B/IV were entered into the HD 3 protocol and received induction chemotherapy with 3× (COPP+ABVD). Patients in complete remission (CR) received consolidation therapy by either radiotherapy (20 Gy IF) or chemotherapy (COPP+ABVD). Patients not in CR received salvage therapy (40 Gy in case of persisting nodal disease, else 4× CEVD chemotherapy). Between July 1983 and May 1987 230 untreated patients aged 15 to 60 qualified for this HD 3 protocol. This analysis is based on the first 137 patients evaluable for response. Of these, 86 (63%) achieved CR after induction chemotherapy. Including salvage therapy a total of 104 patients (76%) achieved CR. Univariate and multivariate prognostic risk factor analyses were performed using freedom from treatment failure (FFTF) as endpoint. Sex, age, splenectomy, bone marrow, liver and bone involvement had no prognostic impact nor had stage according to the Ann Arbor classification. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml appeared as significant risk factors (p〈0.01, relative risk 2.3). The two parameters were not independent. Comparing a group A (ESR ≤ 80 and AP ≤ 230) versus a pooled group B (ESR〉80 and/or AP〉230) increased the difference (p〈0.001, relative risk of 2.8) which was also significant for survival (p〈0.04).
    Type of Medium: Electronic Resource
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