Rapid decrease in cyclic 3'5'-guanosine monophosphate in the earliest phase of acute myocardial infarction.
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Adult↗
Biomedical subjects
B Puschendorf
Publications and source records attributed to B Puschendorf.
Determination of light-chain myosin in pregnancy and under tocolysis.
Cardiac toxicity of tocolysis containing hexoprenaline (0.3 microgram/min) and the beta 1-blocking agent metoprolol (0.01 mg/min) was investigated using a recently developed monoclonal antibody arised against light-chain myosin in 15 patients and compared with the results in 51 control subjects. There was an increase in the median and 80th percentile values 2, 6, 12 and 24 hours after the beginning of tocolysis but no statistically significant difference between these values and the normal ones could be shown.
Coronary Disease↗
[Myoglobin, L-myosin and cGMP--new laboratory parameters in cardiology].
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Creatine Kinase↗
Influence of blood pressure, heart rate, age, and sex on concentrations of atrial natriuretic factor and cyclic GMP in 124 volunteers.
The significance of increased atrial natriuretic factor (ANF) in relation to blood pressure and age is still controversial. We investigated the influence of blood pressure, age, and some other variables on ANF and its putative second messenger, cGMP. Samples for ANF and cGMP detection were taken from 124 ostensibly healthy individuals who were donating blood. Samples were also collected from 27 volunteers before and after blood donation, to study the influence of bleeding. During blood donation, ANF increased from 78.9 to 87.4 ng/L (P = 0.0035), whereas cGMP remained unchanged. ANF concentrations in 124 healthy individuals, corrected for the influence of bleeding, were 61.5 (SD 26.1) ng/L, with a 95% confidence interval of 10.0 to 112.1 ng/L. Mean cGMP concentrations in plasma were 2.9 (SD 1.45) nmol/L, with a 95% confidence interval of 0.4 to 5.75 nmol/L. Multivariance analysis revealed no significant influence of blood pressure, age, heart rate, or sex on concentrations of either ANF or cGMP in plasma.
Adult↗
Separation of Friend erythroleukaemic cell histones and high-mobility-group proteins by reversed-phase high-performance liquid chromatography.
A procedure for the rapid separation of histones and high-mobility-group (HMG) proteins from Friend erythroleukaemic cells (line F4N) by reversed-phase high-performance liquid chromatography is reported. By using a Nucleosil 300-5 C4 column and a multistep water-acetonitrile gradient containing 0.1% trifluoroacetic acid, the HMG-1 and HMG-2 proteins, several H1 subfractions including H1(0), H4, H2B, two H2A variants and two H3 subfractions were separated. Under changed conditions, by applying a varied acetonitrile gradient system, even two H2B variants were fractionated. The methods described seem to be a real alternative to the time-consuming polyacrylamide gel electrophoresis.
Cell Line↗
A new h.p.l.c. isolation procedure for chicken and goose erythrocyte histones.
Total chicken erythrocyte histones were separated by reversed-phase h.p.l.c. using a multi-step acetonitrile gradient in a very short time (35 min). The proteins were eluted in the following order: H1, H5, H2B, H2A.2, H4, H2A.1 and H3.2. Applying a special gradient system adapted for the separation of very-lysine-rich histones, chicken erythrocyte H5 was resolved into two subfractions. Their electrophoretic mobilities were identical in both SDS and acetic acid/urea/Triton polyacrylamide-gel electrophoresis, but different in free-flow electrophoresis. Amino-acid-sequence analyses revealed that the two components only differ with respect to position 15, one having glutamine in that position and the other arginine. A separation of histones prepared from goose erythrocytes disclosed no H5 subfractionation. Furthermore, histones obtained from anaemic-chicken blood were analysed by the above-mentioned h.p.l.c. conditions. An alteration in the relation of H1 to H5 was detected, but no further differences in the number and quantity of the histones and histone variants were observed as compared with the corresponding proteins processed from normal-chicken blood.
Anemia↗
The maximum of the histone acetyltransferase activity precedes DNA-synthesis in regenerating rat liver.
A pronounced transitory increase of histone acetyltransferase (EC 2.3.1.48) activity before the onset of DNA replication is shown to occur in regenerating rat liver. This effect is followed by an increase in the H1/H1(0) ratio at the start of DNA synthesis; H1(0) de is replaced by H1. Histone acetylation and H1/H1(0) exchange are discussed as steps in the signal transduction for DNA replication.
Acetates↗
Atrial natriuretic peptide in AMI.
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Atrial Natriuretic Factor↗
Differential sensitivity of histone acetylation in nitrogen-mustard sensitive and resistant cells. Relation to drug uptake, formation and repair of DNA-interstrand cross-links.
Cultivation of Ehrlich-ascites tumor cells in the presence of N-mustard leads to a selection of cells with a defective choline carrier. As N-mustard employs the choline carrier for transport, this results in reduced drug uptake and in a decrease in drug sensitivity which is specific for N-mustard. Walker carcinoma cells with a stable pleiotropic resistance to a variety of alkylating agents and adriamycin exhibit no evidence for an impaired drug transport and show the same frequency of DNA-interstrand cross-links as the sensitive parental line. Both sensitive and resistant Walker cells exhibit equal capacities for repair of N-mustard induced DNA-interstrand cross-links. The inhibition of histone acetylation by N-mustard, however, was found to be significantly lower in the resistant Walker or Ehrlich cells compared to sensitive counterparts. Although the difference between N-mustard concentrations leading to half maximal inhibition of histone acetylation in sensitive and resistant cells is considerably smaller than the difference between N-mustard doses required for half maximal inhibition of cell proliferation the data suggest that--besides DNA-DNA cross-linking--the inhibition of histone acetylation has to be considered as an important alternative mechanism responsible for the cytotoxic activity of alkylating agents. Inhibition of histone acetylation is not due an accelerated deacetylation and is predominantly expressed in chromatin fractions soluble in 0.1 M NaCl after digestion with micrococcal nuclease.
Acetylation↗
Early decrease in atrial natriuretic peptide in acute myocardial infarction.
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Atrial Natriuretic Factor↗
New aspects of the kinetics of isoenzyme CK-MB during myocardial infarction: discontinuous release?
Intermittent liberation of the serum marker myoglobin is found in acute myocardial infarction, and the ST segment of the electrocardiogram also shows a phasic rise and fall. We therefore measured the serum marker CK-MB at close intervals of time and recorded an oscillation in the serum level. The peaks are not as high as in the serum myoglobin time curve, and it is not easy to decide if they represent the intermittent liberation of the serum marker. It was possible to distinguish between a "high release" and a "low release" group of patients: the former having a maximum CK-MB value of greater than 100 U/l and the latter of less than 100 U/l. Most patients showed 2-3 "initial peaks" within the first 8 h. The highest of these immediately preceded the climb to the definitive maximum value. We conclude that the small size of the peaks in the CK-MB time curve is due to a different mechanism of enzyme release.
Adult↗
Histone separation by high-performance liquid chromatography on C4 reverse-phase columns.
Previous work in our laboratory (Lindner, H., Helliger, W., and Puschendorf, B. (1986) J. Chromatogr. 357, 301-310) described a rapid separation of H1 and core histones by reverse-phase high-performance liquid chromatography using a Bio-Rad Hi-Pore butyl (C4) silica-based column. Despite the short elution time, a high resolution of the different histone fractions, except H4 and H2A (MHP), could be obtained. In this report we present a method for the separation of H4 and H2A (MHP) as well, while maintaining a similar analysis time. By varying the gradient, trifluoroacetic acid concentration (0.05%), and flow rate (1.3 ml/min) the histones were eluted from the C4 column in the following order: H1 (MHP), H1 (LHP), H2B, H2A (LHP), H4, H2A (MHP), H3 (LHP), and H3 (MHP). LHP and MHP refer to less and more hydrophobic histone variants. The identification of the individual protein fractions was performed by comparison the retention times with pure histone markers as well as by gel electrophoresis.
Animals↗
Increased acetylation of histones at an early stage of oestradiol-mediated gene activation in the liver of immature chicks.
The vitellogenin system of chicken was used to examine alterations in the microheterogeneity of chromosomal proteins in the course of steroid hormone-mediated gene expression. After administration of oestradiol-17 beta there is a dramatic increase in the number of copies of vitellogenin m-RNA in the liver of male oviparous animals, like Xenopus and chicken. According to earlier reports the rapid increase in transcriptional activity starts after a lag of 4 h. The system has also been examined as to the number of DNase I hypersensitive sites which appear to correlate with the degree of differentiation and hormonal activation. The time course of [3H]acetate incorporation into the histone fraction was monitored and the microheterogeneity of histones analysed by acid-Triton-urea gel electrophoresis. The results show that there is an increased degree of acetylation of histones in the liver of immature chicks as a result of oestradiol-17 beta administration. The change in the modification pattern of histones was found to be an early event, correlated with the time course of appearance of new DNase I hypersensitive sites and the onset of vitellogenin m-RNA synthesis. These observations are in agreement with an earlier report about the increase in the acetylation of histones in fetal guinea pig uterus after oestradiol treatment [1]. The results suggest that the acetylation of histones might be a prerequisite for the removal of structures for efficient gene repression and the establishment of DNase I hypersensitive sites.
Acetylation↗
Alkylating antitumor agents reduce histone acetyl-transferase activity.
N-Mustard depresses the acetylation of histones in Ehrlich ascites and Walker carcinoma cells. It is demonstrated that this effect is not caused by an accelerated deacetylation but is due to an inhibition of the acetyl-transferase reaction. Employing 4-sulphonatoethylthio-cyclophosphamide it is demonstrated that the alkylating agent affects predominantly the acetylation of a chromatin fraction which is soluble in 0.1M NaCl after digestion with micrococcal nuclease. After removal of the alkylating agent, the recovery of histone acetylation is relatively slow and--in contrast to the repair of DNA cross-links--characterized by a 4-hr lag period. The reduction of histone acetylation by N-mustard is much less expressed in cells which are resistant to the drug than in the sensitive parental lines. This is in contrast to DNA-interstrand cross-links in Walker cells where both N-mustard sensitive and resistant cells inhibit the same cross-link frequency and identical repair rates. Based on these data it is concluded that the inhibition of histone acetylation may be an important part of the mechanism by which alkylating agents inhibit tumor growth.
Acetylation↗
[Tumor biochemistry as basis for advances in tumor chemotherapy].
Oncogenes, onc-gene products and the concept of autonomous self-stimulation of tumor growth by autocrine production of growth factors are discussed with regard to the development of new antitumor agents. The significance of the plasma membrane as an attractive target in tumor chemotherapy is emphasized. Membrane bound enzymes and related reactions which are involved in growth factor dependent regulation of cell proliferation offer new targets for antitumor chemotherapy. Examples demonstrating the antiproliferative effects of phospholipase-C and calmodulin inhibitors are presented. A synergistic effect of these drugs with alkylating agents is observed. Studies devoted to the improvement of alkylating antitumor agents have also led to the plasma-membrane as a particularly suited target. The same may be true for other antitumor agents like anthracyclines and platinum complexes for which evidence exists implicating the involvement of cellular membranes in the mechanism of cytotoxic action.
Alkylating Agents↗
New perspectives on the function of coronary artery spasm in acute myocardial infarction: the thromboischemic reentry mechanism. A review of 10 years research on the pathophysiology of AMI.
Research during the last ten years into the pathophysiology of acute myocardial infarction (AMI) has made it gradually clearer that this is a phasic event. A number of independent authors have made this conclusion quite obvious. The authors of this review suggest that the alternating sequence of coronary spasm and dilatation should be described as the "thromboischemic reentry mechanism," which itself leads to waves of reperfusion, producing characteristic episodic changes in some of the parameters of AMI. The spasms are brought about by substances let loose from aggregating platelets. Metabolites released during the concomitant ischemia lead the vessel from spasm to dilatation. Following thrombolytic treatment, the 'staccato' signs of myoglobinemia disappear, because of the withdrawal of the spasmogenic products of the platelets. It could also be shown that the concentration of myoglobin in the serum as a result of the dilating effect of calcium antagonists is twice the mean maximum value that the myoglobin time curve would show without such treatment.
Animals↗
Effects of the lipidperoxidation product 4-hydroxynonenal and related aldehydes on proliferation and viability of cultured Ehrlich ascites tumor cells.
The mechanism by which the lipid peroxidation product 4-hydroxynonenal and several other homologous, yet non biogenic aldehydes inhibit proliferation of cultured Ehrlich ascites tumor cells has been studied. Incubation of cells (5 X 10(-4)/ml) in a minimum essential medium supplemented with 10 or 20 microM 4-hydroxynonenal reduces the 36-hr cell count to 65 and 30% of the control value. The reduced growth rate is most likely due to a blockage of the DNA synthesis. Cells labelled by a [3H]-thymidine pulse prior to exposure to 4-hydroxynonenal (20 microM, 8 hr) showed no change of the specific radioactivity of the DNA, indicating that no de novo synthesis occurred in the presence of the aldehyde. In the absence of the aldehyde the specific radioactivity of the DNA decreased by 25%. A 2-hr incubation in the presence of 10 or 20 microM of 4-hydroxynonenal reduced [3H]-thymidine incorporation into the HClO4 insoluble fraction to 85 and 50% of the controls, but had no effect of the [3H]-thymidine and 86Rb uptake. Moreover, examination of the cell cultures by the Trypan Blue exclusion technique revealed that 20 microM 4-hydroxynonenal does not cause cell death. The high reactivity of 4-hydroxynonenal towards sulfhydryl groups suggests that the aldehyde inhibits DNA synthesis by interacting with a functional SH group of DNA polymerase. The specific action on DNA synthesis is abolished at an aldehyde concentration of 50 microM, which leads to 30% (6 hr exposure) and 95% (36 hr exposure) of dead cells. The cytostatic index (CI), i.e. concentration at 50% Trypan Blue positive cells/concentration at 50% inhibition of cell growth deducted from the dose effect curves is 3.0 for 4-hydroxynonenal. The other homologous 4-hydroxyalkenals with chain length of 5, 6, 7, 8, 10 and 11 carbon atoms also inhibit cell growth. The CI varied from 1.20 to 1.94, indicating that these non biogenic 4-hydroxyalkenals have a distinctively lower specific effect on proliferation than the biogenic 4-hydroxynonenal. The Michael adducts of 4-hydroxynonenal with glutathione and cysteine were nearly one order of magnitude less toxic than the free aldehyde, the CI (2.41 cysteine adduct, 2.06 glutathione adduct), however, were not improved since the growth inhibitory action was also reduced.
Aldehydes↗
RNA polymerase activity and template activity of chromatin after butyrate induced hyperacetylation of histones in Physarum.
We have studied the effect of sodium-n-butyrate on endogenous RNA polymerase in Physarum polycephalum. 1 mM butyrate strongly reduces RNA polymerase activity measured in isolated nuclei or chromatin; both RNA polymerase A as well as the alpha-amanitin sensitive RNA polymerase B are equally affected. Despite a concomitant hyperacetylation of histone H4 the template activity of chromatin, as analyzed by in vitro transcription of the chromatin with exogenous RNA polymerase from E. coli or RNA polymerase II from wheat germ, remains unaltered as compared to untreated control chromatin, indicating that there is no positive correlation between histone acetylation and template activity of chromatin for transcription in this organism. The results further indicate, that butyrate acts primarily as a quick but reversible inhibitor of protein synthesis in Physarum; the fast decrease of endogenous RNA polymerase activity after butyrate treatment is due to inhibition of enzyme synthesis rather than inactivation of other factors necessary for transcription.
Acetylation↗