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B Behnke

Publications and source records attributed to B Behnke.

34 records · Page 2Linked to original sources
PubMed1996

[Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid].

Urtica dioica extract is a traditionary used adjuvant therapeutic in rheumatoid arthritis. The antiphlogistic effects of the urtica dioica folia extract IDS 23 (Extractum Urticae dioicae foliorum) and the main phenolic ingredient caffeic malic acid were tested concerning the inhibitory potential on biosynthesis of arachidonic acid metabolites in vitro. The caffeic malic acid was isolated from Urtica folia extract using gel exclusion- and high performance liquid chromatography and identified by mass spectroscopy and nuclear magnetic resonance. Concerning the 5-lipoxygenase products IDS 23 showed a partial inhibitory effect. The isolated phenolic acid inhibited the synthesis of the leukotriene B4 in a concentration dependent manner. The concentration for halfmaximal inhibition (IC50) was 83 microns/ml in the used assay. IDS 23 showed a strong concentration dependent inhibition of the synthesis of cyclooxygenase derived reactions. The IC50 were 92 micrograms/ml for IDS 23 and 38 micrograms/ml for the caffeic malic acid. Calculating the content in IDS 23 the caffeic malic acid is a possible but not the only active ingredient of the plant extract in the tested assay systems. It is demonstrated that the phenolic component showed a different enzymatic target compared with IDS 23. The antiphlogistic effects observed in vitro may give an explanation for the pharmacological and clinical effects of IDS 23 in therapie of rheumatoid diseases.

Animals↗
PubMed1996

Bone mineral density in pediatric patients after renal transplantation.

To evaluate the natural history of bone mineral density after successful renal transplantation (TPL) modulated by therapeutic strategies in pediatric patients we have studied peripheral and partially proximal quantitative computed radius tomography (XCT) differentiating between trabecular (TBD), cortical (CBD) and total bone density (BD) cross-sectionally in a group of 24 subjects (mean age 17.1 +/- 7.0 y, mean Scr 1.66 +/- 0.89), 66.1 months (5-260) post transplant and compared the results with 12 controls. After TPL median TBD was elevated (182.5 vs. 155.5 mg/cm3) whereas the opposite was true for CBD (361.8 vs. 437.8 mg/cm3). The physiologic age dependency of BD had got lost after TPL but could be reassumed by the measurement of proximal CBD. TBD correlated with the cumulative calcitriol dosage (r = 0.60, p < 0.05), bone alkaline phosphatase (r = 0.55, p < 0.01), the Ca x P product (r = 0.43, p < 0.05) and inversely with the time after TPL (r = -0.45, p < 0.05), but no significant correlation could be detected with the cumulative steroid dose. It was found to be higher in calcitriol treated than in vitamin D3 treated patients. Proximal CBD was inversely correlated with bone alkaline phosphatase (r = -0.71, p < 0.01) and intact PTH (r = -0.59, p < 0.05). In conclusion CBD in kidney grafted pediatric patients seems to be more or less reduced by secondary hyperparathyroidism whereas the increase of TBD appears to be induced by anticipated calcitriol treatment under dialysis regimen and gradually normalizes after TPL.

Adolescent↗
PubMed1996

[The in vitro induction of monocyte chemotactic protein-1 and interleukin-8 in whole human blood by low molecular weight thymus peptides].

Thymic peptides show immunoreconstitutive und tumor suppressive effects. They are used in oncology to improve the immunological status of patients. Chemokines are able to activate immune cells and inhibit tumor growth. In this study it was proved whether low molecular thymic peptides are able to increase the secretion of the chemokines monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), macrophage inflammatory protein-1 alpha (MIP-1 alpha) and macrophage inflammatory protein-1 beta (MIP-1 beta) as well as the cytokine tumor necrosis factor-alpha (TNF-alpha) which is not related to chemokines using cell cultures of human whole blood. The thymic peptides induced a significant (p < 0.05) elevated secretion of MCP-1 and IL-8 whereas for MIP-1 alpha, MIP-1 beta and TNF-alpha no significant chances were seen. MCP-1 and IL-8 showed divergent dose-dependent effects and a different time kinetic of their secretion. The MCP-1 concentration correlated positively with the count of monocytes in whole blood of the volunteers while the IL-8 concentration in dependence with the incubation time correlated positively with the count of granulocytes or monocytes of the volunteers. The results indicate an activation of monocytes and/or granulocytes by low molecular thymic peptides followed by selective elevated secretion of MCP-1 and IL-8.

Adult↗
PubMed1994

Melatonin inhibits LDL receptor activity and cholesterol synthesis in freshly isolated human mononuclear leukocytes.

There is some indirect evidence that the pineal hormone melatonin can suppress plasma levels of cholesterol in hypercholesterolemic rats. We have examined the effects of the hormone on cellular cholesterol metabolism in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 20 h in a lipid-free medium resulted in an increase in the rate of cholesterol synthesis from [14C]acetate and the high affinity accumulation and degradation of [125I]labeled low density lipoprotein (LDL). Addition of melatonin in increasing concentrations to the incubation medium at zero time inhibited cholesterol synthesis and the specific accumulation and degradation of [125I]labeled LDL; at a concentration of 100 microM, the inhibitions were 38%, 42%, and 48%, respectively. Similar results were obtained using [14C]mevalonate as precursor. Fatty acid synthesis was not altered under these conditions. In contrast to cholesterol, the synthesis of the first cyclic compound lanosterol was not affected by the pineal hormone. These results implicate that melatonin inhibits this pathway between lanosterol and cholesterol. The action of melatonin on LDL receptor activity appeared to be mediated by a decrease in the number of LDL receptors and not by a change in binding affinity. Pharmacological characterization of the potential melatonin receptor site using several analogs like tryptamine, 5-hydroxytryptamine,N-acetyl-5-hydroxytryptamine, 5-methoxytryptamine, and 6-chloromelatonin indicated that the 5-methoxy group is indispensible for the hormone action on cholesterol synthesis. The data provide evidence that melatonin can modulate cholesterol metabolism in human cells.

5-Methoxytryptamine↗
PubMed1994

Inhibition of fatty acid synthesis by stimulation of alpha- and beta-adrenergic receptors in human mononuclear leukocytes.

Selective alpha- and beta-adrenergic agonists and antagonists were used to determine the action of catecholamines on fatty acid biosynthesis in freshly isolated human mononuclear leukocytes. Incubation of cells for 22 h in a lipid-free medium resulted in a 4-fold increase in the incorporation of [14C]acetate into fatty acids. Addition of (-)-epinephrine in increasing concentrations to the incubation medium inhibited the rate of fatty acid synthesis by 42% at a concentration of 0.1 M. Similar effects were observed using (-)-norepinephrine and the beta-agonist isoproterenol. The catecholamine action was diminished by the unselective beta-blocker propranolol and mimicked by dibutyryl cyclic AMP. Since human mononuclear leukocytes possess beta 2-, but not beta 1-adrenoceptors (Brodde, Engel and Hoyer 1981), catecholamines may act via beta-adrenergic receptors of the beta 2-subtype. In addition, it appears that stimulation of alpha-adrenergic receptors inhibits fatty acid synthesis, too. In the presence of a beta-blockade by 1 microM propranolol, the alpha 2-agonist alpha-methylnorepinephrine, but not the alpha 1-agonist phenylephrine inhibited fatty acid synthesis rate. Accordingly, the epinephrine effect was attenuated by the alpha 2-antagonist yohimbine, but not by the alpha 1-antagonist prazosin. The results provide evidence that catecholamines may inhibit the synthesis rate of fatty acids by stimulation of both, beta 2- and alpha 2-adrenergic receptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Endocrine effects of Lycopus europaeus L. following oral application.

Lycopus extracts are used in folk medicine for the treatment of hyperthyroid symptoms. Diverse effects on the pituitary thyroidal system as well as on the pituitary gonadal system could be confirmed in experimental studies. But till now endocrine effects of Lycopus extracts in experimental animals were observed after parenteral application only. Therefore in this investigation an ethanolic extract of Lycopus europaeus was applied orally to rats, diverse endocrine parameters were measured between 3 and 24 h later and the effects compared to an i.p. treated group. The plant extract given p.o. caused a long lasting (for a period of more than 24 h) decrease of T3 levels, presumably as a consequence of a reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid stimulating hormone (TSH) concentrations was observed 24 h after application of the test solution by gavage. The luteinizing hormone (LH) decrease as well as the TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate a central point of attack of the plant extract. Differences in the biological activity in dependence on the route of application may be explained e.g. by differences in absorption of plant constituents.

Animals↗
PubMed1991

Pertussis toxin inhibits autophosphorylation and activation of the insulin receptor kinase.

Pertussis toxin is an ADP-ribosyltransferase which alters the function of some of the GTP-binding proteins and inhibits some actions of insulin. In vivo, pertussis toxin (2 micrograms/ml/2h) inhibited insulin-stimulated tyrosyl autophosphorylation of the insulin receptor by 50% in FaO cells, and nearly completely inhibited phosphorylation of the cellular insulin receptor substrate pp185. Similarly, insulin-stimulated autophosphorylation and kinase activity of the insulin receptor purified on wheat germ agglutinin-agarose from pertussis toxin-treated FaO cells was diminished 50%; however, treatment of cells with the catalytically inactive B-oligomer of the toxin had no effect on receptor tyrosine kinase activity in vitro. Pertussis toxin did not alter insulin binding or the cellular levels of ATP, cAMP, and cGMP. Furthermore, immunoprecipitation of the insulin receptor from intact cells with anti-insulin receptor antibodies showed that pertussis toxin did not increase the phosphorylation of serine or threonine residues in the insulin receptor. These results suggest that pertussis toxin can modulate signal transduction of insulin at the level of the insulin receptor kinase.

Animals↗
PubMed1988

DNA polymerase alpha-DNA primase from human lymphoblasts.

The DNA polymerase alpha-DNA primase complex from the human lymphoblast line HSC93 has been enriched to near homogeneity by using an immunoaffinity purification protocol which was developed earlier for the purification of the calf thymus enzyme (Nasheuer, H.-P. and Grosse, F. (1987) Biochemistry 26, 8458-8466). Immunoaffinity purified polymerase-primase from human cells consisted of four subunits displaying molecular weights of 195,000 and 180,000 for the DNA synthesizing alpha-subunit, of 68,000 for the beta-subunit, and of 55,000 and 48,000 for the primase-carrying gamma- and delta-subunit, respectively. The isoelectric pH values for the individual subunits were estimated from non-equilibrium pH gradients to be between 5.9 and 5.7 for the alpha-subunit, at 5.5 for the beta-subunit, and at 7.5 and 8.0 for the gamma- and delta-subunit, respectively. The purified polymerase-primase converted single-stranded phi X174 DNA into the double-stranded form in a primase-initiated reaction. During this process, 3-10 RNA primers were formed. RNA primers were about 11 nucleotides long. Elongation of existing RNA primers by the human polymerase-primase was semi-processive; following primer binding the DNA polymerase continuously incorporated 20 to 50 nucleotides, then it dissociated from the template DNA.

Bacteriophage phi X 174↗
PubMed1988

Immunoquantitation and size determination of intrinsic poly(ADP-ribose) polymerase from acid precipitates. An analysis of the in vivo status in mammalian species and in lower eukaryotes.

Antibodies against pig thymus poly(ADP-ribose) polymerase were obtained with enzyme-hemocyanin conjugates and used for immunoquantitation. The quick-blot procedure used allowed the determination of amounts as low as 1 ng of enzyme from whole cell trichloracetic acid precipitates. When applied to analysis of various human, rodent, and bovine cell types, surprisingly similar amounts of polymerase were found (1-5 ng of pig thymus polymerase equivalents/micrograms of DNA, 2 X 10(5) polymerase molecules/HeLa cell). Also, no significant difference was seen between normal and transformed cells. Polymerase tended to decline in several fibroblast cultures upon reaching confluency, which was not reflected by total polymerase activity. Divergence between total activity and immunogenic equivalents was also seen in alkylated cells and in rat liver treated with phenobarbital. Trichloroacetic acid-insoluble fractions dissolved in sodium dodecyl sulfate buffer could also be used to analyze, by Western blotting, the size distribution of poly(ADP-ribose) polymerase in vivo. Application to various cell types revealed that all mouse and rat cells tested had two immunogenic bands (116 and 98 kDa) of similar intensity. A highly conserved structure of poly(ADP-ribose) polymerase may be deduced from the existence of immunogenic and renaturable 116-kDa polypeptide bands even in the low eukaryotes Physarum polycephalum and Dictyostelium discoideum.

Animals↗
PubMed1988

Regulation of sterol synthesis by histamine in human mononuclear leukocytes: roles of H1- and H2-receptors.

The effect of histamine on sterol synthesis has been investigated in freshly isolated human mononuclear leukocytes from healthy subjects. Incubation of cells for 6 h in a medium containing lipid depleted serum led to a threefold increase in the incorporation of (14C)-acetate or tritiated water into sterols. Histamine 0.3 microM added to the incubation medium at zero time inhibited this induction by 35% with a sigmoidal log dose-effect curve. The receptors mediating this action were characterised pharmacologically by using selective H1- and H2-agonists and -antagonists. The H2-agonists impromidine and 4-methylhistamine mimicked the effect of histamine on sterol synthesis, the suppression being 42% and 31%, respectively, at a concentration of 1 microM. In contrast, the H1-agonist 2-pyridylethylamine did not affect the pathway. The H2-antagonist cimetidine (10 microM) but not the H1-antagonist mepyramine (10 microM) totally reversed the inhibition of sterol synthesis by histamine. The results provide evidence that sterol synthesis in human mononuclear leukocytes is regulated by histamine, which appears to act predominantly via H2-receptors.

Cimetidine↗
PubMed1988

Opposite effects of insulin and catecholamines on LDL-receptor activity in human mononuclear leukocytes.

The mechanisms by which insulin and catecholamines affect low-density lipoprotein (LDL)-receptor activity were studied in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 24 h in a lipid-free medium resulted in an increase in the specific binding, accumulation, and degradation of 125I-labeled LDL. Insulin stimulated the ability of the cells to bind, accumulate, and degrade the lipoprotein with high affinity, which may be caused by an increase in the LDL-receptor number without altering binding affinity. (-)-Epinephrine inhibited the specific binding, accumulation, and degradation of 125I-LDL. This effect appears to be mediated by a decrease in the number of LDL receptors and not by a change in the binding affinity. (-)-Norepinephrine, the unspecific beta-adrenergic agonist (-)-isoproterenol, and the beta 2-specific agonist terbutaline mimicked the effect of epinephrine on LDL-receptor activity. Catecholamines and beta-adrenergic agonists yielded sigmoidal log-concentration effect curves. The action of epinephrine was attenuated by the beta-antagonist (dl)-propranolol. These results demonstrate that insulin stimulates and catecholamines suppress the specific binding, accumulation, and degradation of 125I-LDL in human mononuclear leukocytes. The catecholamine action appears to be mediated by beta 2-adrenergic receptors. A suppression of LDL-receptor activity resulting from deficiency of insulin and elevated plasma catecholamine concentrations in uncontrolled insulin-dependent diabetic patients may contribute to the increased levels of LDL cholesterol observed in these patients.

Catecholamines↗
PubMed1988

Effects of prostaglandins on LDL receptor activity and cholesterol synthesis in freshly isolated human mononuclear leukocytes.

The effects of prostaglandin (PG) E1, PGE2, the stable prostacyclin analogue Iloprost, and PGF2 alpha on low density lipoprotein (LDL) receptor activity and cholesterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 45 hr in a lipid-free medium resulted in an increase in the rate of cholesterol synthesis from [14C]acetate and the high affinity accumulation and degradation of 125I-labeled LDL. Addition of PGE1 in increasing concentrations to the incubation medium inhibited cholesterol synthesis and the specific accumulation and degradation of 125I-labeled LDL; at a concentration of 10 microM, the inhibitions were 61%, 70%, and 67%, respectively, after an incubation of 20 hr. The effects of PGE2 and Iloprost were similar. The action of the prostaglandins on LDL receptor activity appeared to be mediated by a decrease in the number of LDL receptors and not by a change in the binding affinity. The prostaglandins yielded sigmoidal log concentration-effect curves. In contrast, PGF2 alpha had no influence on cholesterol synthesis or LDL receptor activity up to a concentration of 10 microM. PGE1, PGE2, and Iloprost, but not PGF2 alpha, led to an increase in the concentration of intracellular cyclic AMP. Dibutyryl cyclic AMP mimicked the effects of the E-prostaglandins and Iloprost on the LDL receptor activity. The results suggest that PGE1, PGE2, and prostacyclin affect LDL receptor activity and cholesterol synthesis and, therefore, may play a role in the regulation of cholesterol homeostasis and in the development of atherosclerosis.

Acetates↗
PubMed1987

Effects of calcium antagonists and adrenergic antihypertensive drugs on plasma lipids and cellular cholesterol metabolism.

Calcium antagonists and antihypertensive alpha-adrenergic and beta-adrenergic drugs may cause changes in plasma lipoprotein levels. Different mechanisms by which these antihypertensive agents effect cellular lipid metabolism have been proposed. The activity of lipoprotein lipase that determines the catabolism of very low density lipoproteins (VLDL) is decreased by the beta-blocker propranolol and increased by alpha 1-antagonists. The plasma cholesterol or low density lipoprotein (LDL) level is inversely associated with the number of LDL receptors. Catecholamines suppress the LDL receptor activity, thus leading to an increase in plasma cholesterol concentration. The calcium antagonist verapamil and the beta-blocker propranolol may increase LDL receptor activity either per se or by its antagonizing effect on the catecholamine action. The metabolism of high density lipoproteins (HDL) may be affected directly by catecholamines, which might increase HDL binding activity, thereby enhancing efflux of cholesterol from cells. Catecholamines inhibit cholesterol biosynthesis in extrahepatic cells. The effects are mediated by alpha 2- and beta 2-adrenergic receptors. Accordingly, the alpha 2-agonists clonidine and alpha-methyldopa mimicked and propranolol opposed the catecholamine action. In contrast, the alpha 1 antagonists indoramin, prazosin, and urapidil had no effect on cholesterol synthesis. The results provide evidence that calcium antagonists and various antihypertensive drugs, depending upon their action on beta- or alpha-adrenergic receptors, affect lipid metabolism differently. The metabolic effect may play a role in atherogenesis and may be of clinical importance when antihypertensive treatment is considered.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

The recombinant human histones H1 zero and H1.2 cause different toxicity profiles on the human leukemia cell line K562.

The human histones H1 zero and H1.2 were expressed in E. coli and purified to homogenity. Their cytotoxicity on the human leukemia cell line K562 and on PBMC from healthy volunteers was compared with the cytotoxic effect of a bovine histone H1 preparation. In this preparation, histone H1.2 was identified as the main compound. All three histone preparations induced a significant dose-dependent toxicity on the leukemia cell line. Compared with the recombinant histone H1 zero, the bovine preparation and recombinant H1.2 showed stronger cytotoxicities. Cytotoxic effects on K562 cells were observed immediately after addition of the histones, whereas the histone preparations failed to induce significant cytotoxicity on PBMC during the first hour of incubation. However, after 24 hours all three histone preparations induced toxic effects on PBMC which were comparable to those observed on the leukemia cell line.

Animals↗
PubMedDate not supplied

Low molecular thymic peptides stimulate human blood dendritic cells.

Dendritic cells are considered to be the most potent antigen-presenting cells and are thus promising new tools for the immunotherapy of cancer. They respond to various stimuli by differentiation (expression of CD83) and up-regulation of costimulatory surface molecules. Thymic peptides have immunostimulatory and immunomodulating properties. Their therapeutic potential in immunotherapy of cancer has been discussed. To test whether thymic peptides act on dendritic cells, we examined the effects of a standardized thymic peptide preparation on cultured human monocyte-derived dendritic cells. Addition of thymic peptides resulted in enhanced expression of the specific differentiation marker CD83 in a dose dependent manner. Moreover, thymic peptides induced the up-regulation of costimulatory molecules including CD86, CD80, HLA-DR and HLA-ABC. After priming with thymic peptides dendritic cells showed an enhanced expression of IL-8 and TNF-alpha mRNA and protein release. Dendritic cells stimulated with thymic peptides were able to induce proliferation of autologous T cells as measured by 3H-thymidine incorporation in mixed Lymphocyte reaction. In combination with a low dosage of keyhole limpet hemocyanin, thymic peptides showed additive effects in the up-regulation of CD83 and costimulatory surface markers. Our findings indicate that thymic peptides per se act on professional antigen-presenting cells in a stimulatory manner and were presented by these cells. Furthermore, thymic peptides enhance the response of dendritic cells to low dosages of a standard nominal antigen. Therefore, thymic peptides could improve the immunological activity especially against low amounts of endogenous antigens.

Amino Acid Sequence↗