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Biomedical subjects

E Lengfelder

Publications and source records attributed to E Lengfelder.

At least 73 records · Page 4Linked to original sources
PubMed1986

High-dose cytosine-arabinoside and mitoxantrone in refractory acute myeloid leukemia: a clinical phase I/II-study.

In a multi-institutional study 26 patients with refractory acute myeloid leukemia were entered into a phase I/II study of HD-ara-C and mitox. HD-ara-C 3 g/m2 q 12h was given by 3h infusion on days 1-4. Mitox was started at 12 mg/m2/d on days 3, 4 and 5, and escalated to 4 and 5 doses of 10 mg/m2/d on days 2-5 and 2-6, respectively. From 24 patients presently evaluable for response, 12 achieved a CR and 2 a PR. 7 patients died of infectious complications within the first 4 weeks of treatment while persistent AML was found in 3 cases. Except for one death, possibly related to acute cardiomyopathy, toxicity was mild to moderate consisting of nausea and vomiting, mucositis and diarrhea. These data indicate a high anti-leukemic activity of HD-ara-C/mitox in AML refractory against conventional chemotherapy.

Anthraquinones↗
PubMed1986

Effects of hyperthermic conditions on the reactivity of oxygen radicals.

Generation and reactivity of superoxide (O2.-) and hydroxyl (OH.) radicals in enzymatic and radiolytic systems were investigated over the temperature range from 20 degrees-50 degrees C. The generation rate and reaction kinetics of both enzymatically and radiolytically produced superoxide radicals were determined by a cytochrome c reduction assay. For OH. radical reaction studies the degradation of hyaluronic acid was assayed. An increase in temperature leads to a greater reactivity of both radicals, but in the case of an enzymatic source a disproportionate increase in the rate of generation is observed. In the pulse radiolysis system, the reactivity of superoxide radicals was found to be stimulated 15-fold over the temperature range from 20 degrees C to 60 degrees C, although the activity of superoxide dismutase was only minimally increased (about 1.6-fold). The results are discussed with respect to the possible importance of active oxygen species to the biological effects of hyperthermia.

Cytochrome c Group↗
PubMed1984

Radical formation during autoxidation of 4-dimethylaminophenol and some properties of the reaction products.

4-Dimethylaminophenol (DMAP), after intravenous injection, rapidly forms ferrihaemoglobin and has been successfully used in the treatment of cyanide poisoning. Since DMAP produces many equivalents of ferrihaemoglobin, it was of interest to obtain further insight into this catalytic process. DMAP autoxidizes readily at pH regions above neutrality, a process which is markedly accelerated by oxyhaemoglobin. The resulting red-coloured product was identified as the 4-(N,N-dimethylamino) phenoxyl radical by EPR spectroscopy. The same radical was also produced by pulse radiolysis and oxidation with ferricyanide. The 4-(N,N-dimethylamino)phenoxyl radical is quite unstable and decays in a pseudo-first order reaction (k = 0.4 sec-1 at pH 8.5, 22 degrees) with the formation of p-benzoquinone and dimethylamine. This observed decay rate is identical with the rate of hydrolysis of N,N-dimethylquinonimine. When a solution containing the phenoxyl radical was extracted with ether, half the stoichiometric amount of DMAP was recovered. Hence it is apparent that the phenoxyl radical decays by disproportionation yielding DMAP and N,N-dimethylquinonimine. The latter product then quickly hydrolyses. The equilibrium of this disproportionation reaction is far towards the radical side, and the pseudo-first order hydrolysis controls the radical decay rate. p-Benzoquinone rapidly reacts with DMAP (k2 = 2 X 10(4) M-1 sec-1) with the formation of the 4-(N,N-dimethylamino)phenoxyl and the semiquinone radicals. This reaction explains the autocatalytic phenoxyl radical formation during autoxidation of DMAP. DMAP is not oxidized by H2O2 or O-.2 but the 4-(N,N-dimethylamino)phenoxyl radical is very rapidly reduced by O-.2 (k2 = 2 X 10(8) M-1 sec-1). In addition, the phenoxyl radical is quickly reduced by NAD(P)H or GSH with the formation of NAD(P)+ or GSSG. Since DMAP is also able to reduce two equivalents of ferrihaemoglobin (provided that the ferrohaemoglobin produced is trapped by carbon monoxide), electrophilic addition reactions of the phenoxyl radical seem unimportant in contrast to N,N-dimethylquinonimine. Hence, during the catalytic ferrihaemoglobin formation, DMAP is oxidized by oxygen which is activated by haemoglobin, and the phenoxyl radical oxidizes ferrohaemoglobin. This catalytic process is terminated by covalent binding of N,N-dimethylquinonimine to SH groups of haemoglobin (and GSH in red cells).

Aminophenols↗
PubMed1980

Structure of Cu2(indomethacin)4 and the reaction with superoxide in aprotic systems.

The copper complex of indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole acetate), a common anti-inflammatory drug, was prepared and characterized. Crystal structure determination revealed the dimeric form of the 1 : 2 complex, namely Cu2(indomethacin)4 x L2, in the unit cell. Surprisingly, the copper-copper distance (263 pm) was very close to metallic copper (256 pm). The two coordination sites in the copper-copper axis can be readily replaced by superoxide. An intriguing similarity to Cu2(acetate)4 was seen. Due to the lipophilic nature of the indomethacin ligand, this copper complex reacted with superoxide in aprotic solvents. the superoxide dismutating activity was successfully demonstrated in Me2SO/water and acetonitrile/water mixtures using the nitro-blue tetrazolium assay and pulse radiolysis. The second-order rate constant of 6 x 10(9) M-1 x s-1 in strictly aqueous systems dropped only slightly to 1.1 x 10(9) M-1 x s-1 when aprotic solvents were used. This is the fastest rate constant ever observed for a copper-dependent dismutation of superoxide. The KO2-induced lipid peroxidation in both erythrocytes and liver microsomes was suppressed by 70% in the presence of 1 x 10(-10) mol x ml-1 of Cu2(indomethacin)4. The inhibitory action dropped to 25% when Cu2Zn2superoxide dismutase was employed. The formation of copper x indomethacin in rat serum after administration of indomethacin was shown in vitro and vivo.

Animals↗
PubMed1980

[Extreme pseudoagglutination of the red blood corpuscles by cold-labile IgM paraprotein (author's transl)].

Electronic cell count and blood smear was impossible because of extreme pseudoagglutination of erythrocytes in a 70-year-old woman with chronic lymphoid leukaemia and associated antibody deficiency. Cold precipitation of citrated plasma occurred at 4 degrees C, turbidity was noted at room temperature, and the plasma was clear at 37 degrees C. Serum immunoelectrophoresis demonstrated IgM paraprotein of kappa type which was also present in the eluate after breaking up the erythrocyte surface at 37 degrees C. This demonstrates that the pseudoagglutination was caused by loading of the red blood corpuscles by a serologically defined cryoglobulin.

Aged↗
PubMed1980

Oxygen utilization by Lactobacillus plantarum. II. Superoxide and superoxide dismutation.

Cell-free extracts of Lactobacillus plantarum contain non-proteinaceous compounds which mimic superoxide dismutase activity. Using the test system in which O-2 is generated by xanthine oxidase, superoxide dismutase activity is found in cell-free extracts, where proteins are removed by precipitation. This activity is strongly decreased after dialysis of cell-free extracts. Superoxide dismutase activity was also investigated by means of pulse radiolysis. Cell-free extracts of Escherichia coli were also investigated as a comparison, which were known to contain superoxide dismutase. With cell-free extracts of both L. plantarum and E. coli the decay of O-2 was markedly increased. However, the type of reaction of the O-2 decay was of first order in the presence of E. coli extracts due to superoxide dismutase(s), and of second order in the presence of L. plantarum extracts, indicating that O-2 elimination is not an enzymic reaction. Mn2+ phosphate(s) might be responsible for the observed elimination of O-2. The production of O-2 is not detectable during NADH-, lactate- or pyruvate oxidase reactions in L. plantarum extracts.

Cell-Free System↗
PubMed1979

Functional aspects of the superoxide dismutative action of Cu-penicillamine.

The superoxide dismutative action of Cu-penicillamine was examined by pulse radiolysis. The second order rate constand of the reaction wpith superoxide was 0.4 +/- o.2.10(9) M-1.s-1, comparable to the action of Fe and Mn-superoxide dismutases. No marked pH-dependence was seen. Neither ethylene diamine tetraacetic acid nor cyanide affected the catalytic action of Cu-penicillamine. The cyanide resistant reactivity as well as further X-ray photoelectron spectrometric measurements supported the suggestion of a Cu(I) stabilized sulphur radical being the active species involved in the catalysis of superoxide dismutation.

Binding Sites↗
PubMed1979

On the action of diethyldithiocarbamate as inhibitor of copper-zinc superoxide dismutase.

The rate constants of the reactions between pulse radiolytically produced superoxide radicals and the Cu(II) chelate of diethyldithiocarbamate were determined at pH 7.0. It was found that diethyldithiocarbamate forms a copper complex, which as no dismutating activity. The removal of the protein bound copper in superoxide dismutase by diethyldithiocarbamate yields the same effect as coordination of the copper in the enzyme.

Animals↗
PubMed1978

Oxygen activation in isolated chloroplasts. Mechanism of ferredoxin-dependent ethylene formation from methionine.

Low-potential electron acceptors of photosystem I of chloroplast lamellae produce superoxide anions (0-2) and hydrogen peroxide by autoxidation, but have no effect on ethylene formation from methionine; equimolar amounts of ferredoxin are less active in photosynthetic O-2 and H2O2 production but strongly stimulate ethylene production from methionine. 2. Ten to fifty units of superoxide dismutase inhibit fifty to two hundred units of superoxide dismutase stimulate ethylene formation from methionine by chloroplast lamellae in the presence of ferredoxin. This stimulation is stronger at pH 7.0 than at pH 7.8. Catalase inhibits ethylene formation from methionine. 3. Pulse-radiolytic production of nitrite (NO-2) from hydroxylamine, initiated by hydroxyl radicals (.OH) or O-2, shows no difference in the presence or absence of ferredoxin, nor do the decay kinetics of O2. 4. From the above observations and from model reactions (xanthine/xanthine oxidase; iron salts in the presence of H2O2), it is concluded that reduced ferredoxin in the presence of H2O2 forms a Fenton-type oxidizing species for methionine, generating ethylene in the presence of pyridoxal phosphate. 5. Inhibitory effects of both superoxide dismutase and catalase in oxygen-dependent reactions need not necessarily indicate the participation of the 'Haber-Weiss' reaction.

Chloroplasts↗
PubMed1978

The involvement of oxygen radicals during the autoxidation of adrenalin.

1. In unbuffered alkaline solutions, autoxidizing adrenalin generates superoxide anions: both the scavenging by adrenalin itself, leading to adrenochrome, and the formation of nitrite from hydroxylamine are inhibited by superoxide dismutase. No hydroxyl radical could be detected. 2. The yield of hydrogen peroxide increases with pH in a way similar to that of adrenochrome and nitrite. The dissociated form of adrenalin (pK = 8.5) is proposed as the source of superoxide anions. 3. Superoxide dismutase delays rather than inhibits the reaction. In addition to the diminished formation of adrenochrome due to the scavenging of superoxide anions and re-reduction of the semiquinone by hydrogen peroxide, respectively, adrenochrome is further removed by hydrogen peroxide, with final products absorbing at 310 nm. 4. The diminished inhibitory effect of superoxide dismutase above pH 10 is due to superoxide-independent reactions. This effect is masked by the alkaline conversion of adrenochrome to indole compounds. 5. It is concluded that monitoring the absorption of adrenochrome in alkaline solutions does not produce reliable evidence for superoxide anions.

Adrenochrome↗
PubMed1978

Determination of the superoxide dismutating activity of D-penicillamine copper.

The superoxide dismutating activity of the D-penicillamine copper complex was determined and compared with the activities of Cu-Zn and Mn superoxide dismutase in four O2 ground negative earth generating systems. I. Nitrite formation from hydroxylamine. II. Crocin destruction by xanthine/xanthine oxidase. III. Ethylene production by isolated chloroplasts. IV. Nitrite formation from hydroxylamine by chloroplasts in the presence of diquat (1, 1'-dimethylene-2,2'-bipyridylium dibromide). In all four test systems a high dismutative activity of the complex was found, which is not sensitive to KCN as demonstrated with test system III. The results are discussed with regard to the antiinflammatory activity of D-penicillamine.

Copper↗