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Biomedical subjects

B Wagner

Publications and source records attributed to B Wagner.

At least 199 records · Page 11Linked to original sources
PubMed1988

W-7 at calmodulin-antagonistic concentrations facilitates noradrenaline release from rat brain cortex slices.

Slices from rat brain occipital cortex were preincubated with [3H]noradrenaline then superfused and stimulated electrically. W-7, 10 mumol/l, enhanced the stimulation-evoked overlow. Binding experiments with W-7 evidenced weak displacement of [3H]yohimbine and no displacement of [3H]prazosin. Release experiments with the addition of clonidine, cocaine or phentolamine provided no evidence for major interference of W-7 with alpha-adrenergic or uptake mechanisms. Facilitation could have been due to inhibition of a calmodulin-dependent enzyme which could not be identified from the present results.

Animals↗
PubMed1988

The inhibitory effects of the novel calcium antagonist Goe 5438 on calcium-dependent processes of excitation and contraction of single cardiomyocytes.

The calcium-antagonistic properties of the novel compound Goe 5438 have been studied in single cardiomyocytes from embryonic (chicken) and adult (guinea-pig) ventricles, in part in comparison with the inhibitory effects of the 1,4-dihydropyridine calcium antagonist nimodipine. Both substances block spontaneous action potentials and contractions of embryonic heart cells at about 0.1 mumol/l. In collagenase-dispersed ventricular cardiomyocytes of guinea-pigs, stereospecific inhibition of the slow calcium current (ICa) by Goe 5438 was observed at 10 mumol/l by means of voltage-clamp experiments. The (+)-enantiomer of Goe 5438 elicited a stronger inhibition of the slow inward current than the (-)-enantiomer. The frequency dependence of the inhibitory effect of Goe 5438 as well as that of nimodipine could be shown to be negligible in measurements of ICa and contractions, whereas the inhibitory influence of verapamil, verified in the same experimental arrangement, exhibited a distinct frequency dependence. With respect to a possible potential dependence of the inhibitory effect of Goe 5438 and nimodipine, it could be shown that a hyperpolarization during the course of application of either calcium antagonist produced recovery of the calcium-dependent excitation neither in adult nor in embryonic cells. In adult cardiomyocytes, the dependence of ICa on the membrane potential was not altered by Goe 5438. It is concluded that the mode of action of Goe 5438 resembles that of 1,4-dihydropyridine calcium antagonists.

Action Potentials↗
PubMed1988

Properties of high and low density subpopulations of group B streptococci: enhanced virulence of the low density variant.

From the group B streptococcus (GBS) reference strain 090 la Colindale two subpopulations, which differed markedly regarding their capacities for biosynthesis of type-specific polysaccharide, were obtained by separation on a hypotonic Percoll density gradient. In the original strain and the high and low density variants, there was a negative correlation between buoyant density and bio-synthesis of type-specific polysaccharide as determined by ultrastructure and quantitative assays. The invasiveness of these variants was investigated by infecting rabbits via subcutaneously implanted tissue cages. In the animals infected with highly encapsulated bacteria, heavy bacteremia was detected 8 h post-infection, whereas in the animals which received high density bacteria with small amount of capsule, heavy bacteremia was not detected until after five days. All isolates recovered from the blood or organs of these rabbits were of the capsule rich phenotype, indicating a phenotypic shift in the subpopulation of high density bacteria. An apparently similar phenotypic shift was noted in an isolate from a baby with early onset septicemia. There was a dominance of low density bacteria in the isolate obtained from the baby as compared with the colonizing population of bacteria isolated from the cervix of the mother. From these type III isolates, subpopulations with different density maxima were obtained. A reversed shifting towards dominance of less encapsulated, high density bacteria was observed during in vitro passage of these subpopulations.

Animals↗
PubMed1988

Investigations on the binding of erythrogenic toxin A of Streptococcus pyogenes on human peripheral blood lymphocytes. II. Identification of toxin-binding lymphocytes and characterization of the receptor.

Gold complexes of erythrogenic toxin A (ETA) of Streptococcus pyogenes (strain NY-5) were bound to human lymphocytes that could be characterized as T cells by rosetting or labelling with OKT 3 antibody and anti-mouse-IgG-gold. Using OKT 4 and OKT 8 antibodies, respectively, it was demonstrated that binding of ETA was confined to the T helper/inducer cell subpopulation. Treatment of lymphocytes with neuraminidase enhanced the binding of ETA-gold, whereas trypsin treatment resulted in its reduction. Gangliosides of type II or type III and D-galactose only slightly decreased the ETA-gold binding. Preincubation of living lymphocytes with the mitogens concanavalin A or the Lens culinaris-lectin enhanced the binding of ETA-gold.

Bacterial Proteins↗
PubMed1988

Biological and biochemical activities of a toxoid of erythrogenic toxin type A.

A toxoid of erythrogenic toxin type A (ET A) was prepared by formaldehyde treatment. Already 15 min after exposure to formaldehyde in isoelectric focusing the ET A band at pH 5.2 shifted to a band at pH 4.5. In Ouchterlony double diffusion test ET A and its toxoid were found to be identical, in fused rocket immuno-electrophoresis a reaction of partial identity was seen. Formaldehyde treatment of ET A resulted in an apparent increase of electrophoretic mobility. In contrast to ET A, its toxoid is non-mitogenic, non-pyrogenic and has lost its ability to induce delayed type hypersensitivity. Binding of ET A toxoid to human peripheral lymphocytes is of the same magnitude as binding of gold-labelled ET A.

Animals↗
PubMed1988

Localization and characterization of fibronectin-binding to group A streptococci. An electron microscopic study using protein-gold-complexes.

The location and nature of the binding sites for fibronectin (Fn) and its N-terminal 29 K fragment (FnF) on group A streptococci were studied by electron microscopy using these proteins labelled with colloidal gold. The investigated strains exhibited a different labelling intensity as well as a different labelling pattern varying from a strong regular distribution to a weak focal binding. Binding of Fn and FnF was inhibited by itself as well as by lipoteichoic acid (LTA), anti-LTA and concanavalin A. Simultaneous labelling of the bacteria with marker complexes of FnF, human serum albumin and fibrinogen revealed separate receptor sites for each protein. Our results confirmed LTA to be mainly responsible for the binding of Fn on group A streptococci.

Binding Sites↗
PubMed1988

Electron microscopic localization of lipoteichoic acid on group A streptococci.

The location of lipoteichoic acid (LTA) on the surface of group A streptococci was studied by immunoelectron microscopic and ultrastructural cytochemical methods, i.e. by means of LTA antibodies labelled with ferritin, or concanavalin A labelled with ferritin or colloidal gold. All these methods proved the LTA to be located on the outer cell surface of most group A streptococcus strains. The differences in the intensity of labelling paralleled the hydrophobicity of the strains, being substantially higher in the strains exhibiting a high degree of hydrophobicity. Treatment of streptococci with pronase or trypsin led to a complete loss of surface-located LTA. On the other hand, pepsin treatment of streptococci under mild conditions resulted in an increased amount of surface-located LTA in some strains. On the isolated cell walls, LTA could be demonstrated only on the outer surface of the walls. These findings correlated well with the presumed role of group A streptococcus LTA in the adherence of streptococci to the epithelial cells which is accomplished with the aid of surface-located LTA molecules.

Bacterial Adhesion↗
PubMed1988

2'-Deoxycoformycin (pentostatin) for lymphoid malignancies. Rational development of an active new drug.

A new antimetabolite, 2'-deoxycoformycin (pentostatin), has striking antitumor activity in several lymphoid neoplasms. Isolated from cultured soil organisms, this purine analogue is a potent inhibitor of adenosine deaminase (ADA), and is thus selectively toxic to lymphocytes. Early clinical trials showed that high doses of pentostatin caused severe and unpredictable toxicity, but responses in refractory lymphoid malignancies were encouraging. Careful pharmacologic studies led to the definition of a safe and effective low weekly dose, at which protracted ADA inhibition occurs in neoplastic cells. The most sensitive tumor identified is hairy cell leukemia, in which durable remissions are achieved in more than 90% of patients with a relatively brief course of treatment. Other responsive diseases include chronic lymphocytic leukemia, prolymphocytic leukemia, mycosis fungoides, and acute T-cell lymphoma or leukemia. Response has been seen in acute lymphocytic leukemia, but the higher doses required are substantially more toxic. Pentostatin is valuable for treatment of indolent lymphoid malignancies and may be useful in non-cancer-related lymphocyte research.

Adenosine Deaminase Inhibitors↗
PubMed1987

Phorbol 12,13-dibutyrate-induced contraction of isolated rabbit vascular smooth muscle.

The contractile effects of the phorbol-12,13-dibutyrate (PDBu) on rabbit basilar, renal, and saphenous arterial rings were investigated under various bathing conditions. At millimolar concentrations of Ca2+, the contractile responses with respect to both maximal contraction and sensitivity to PDBu were in the rank order basilar artery greater than renal artery greater than saphenous artery. Contractions were induced by PDBu also at micromolar concentrations of Ca2+. Depolarization of the cell membrane in the presence of micromolar Ca2+, which did not result in contraction of the vascular rings, caused a shift of the concentration response curves towards lower PDBu concentrations. These results are compatible with the assumption that PDBu induces contraction in vascular smooth muscle by activating protein kinase C.

Animals↗
PubMed1987

Stereoselective inhibition of calmodulin-dependent cAMP phosphodiesterase from bovine heart by (+)- and (-)-nimodipine.

The inhibitory effects of racemic (+/-)-nimodipine and of optically pure (+)- and (-)-nimodipine on the basal and calmodulin-dependent activity of a cAMP phosphodiesterase from bovine heart were investigated. The inhibition by (+/-)-nimodipine could not be overcome by an excess of calmodulin. However, increase of the cAMP concentration in the assay from 2 X 10(-4) mol/l to 2 X 10(-2) mol/l caused a shift of the IC50 for the inhibition by (+/-)-nimodipine from 2.8 X 10(-6) mol/l to 6 X 10(-5) mol/l. Dixon-plot analysis revealed an inhibitory constant of Ki = 2.3 mumol/l. Experiments with the two enantiomers showed that (+)-nimodipine is by about one order of magnitude more potent than (-)-nimodipine. This contrasts with the stereoselectivity of the Ca2+ channel inhibitory activity on isolated rings of the rabbit basilar artery where (-)-nimodipine is more effective than (+)-nimodipine in relaxing the smooth muscle contracted by K+-depolarisation. It is concluded that cAMP phosphodiesterase may be an intracellular target for nimodipine and its inhibition may contribute to the pharmacological activity of this 1,4-dihydropyridine.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Effect of progestins, androgens, estrogens and antiestrogens on 3H-thymidine uptake by human endometrial and endosalpinx cells in vitro.

The present study describes the effects of 11 steroid hormones and 3 non-steroidal antiestrogens on the 3H-thymidine uptake by human endometrial and endosalpinx cells in long-term cultures. The compounds were added in various concentrations ranging from 10(-9) to 10(-4) M. Progesterone and 19-nortestosterone caused a dose-dependent reduction of the 3H-thymidine incorporation resulting in a 94-98% inhibition at a concentration of 10(-4) M, gestonoroncaproate and d,1-norgestrel were less effective causing a 49% and 40% decrease. Antiproliferative effects were also noted after the addition of androgens (testosterone, 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone and danazol). The inhibitory effect of testosterone was equivalent to progesterone at concentrations of 10(-4) M. The addition of estrogens (estrone, estradiol-17 beta and estriol) and antiestrogens (tamoxifen, N-desmethyl- and 4-OH-tamoxifen) produced a dual response in monolayer cultures as low concentrations (10(-9)-10(-6) M) were associated with a slightly increased 3H-thymidine incorporation while pharmacological concentrations (10(-5)-10(-4) M) were followed by a significant decrease. Cells originating from the endosalpinx did not respond to either estradiol-17 beta or progesterone. These results suggest that in contrast to endometrium, the proliferation of endosalpinx cells is independent of sex steroids.

Androgens↗
PubMed1987

Similar effects of ralitoline and phenytoin on papillary muscle action potentials: evidence for sodium antagonistic activity.

Ralitoline is a new anticonvulsant, the profile of which most closely resembles that of phenytoin. Using papillary muscles isolated from guinea pig hearts, action potentials (APs) were elicited (0.5 Hz) and measured intracellularly. No significant effects on resting membrane potential, AP duration, and AP amplitude were observed up to 100 microM with both drugs. Ralitoline reduced dV/dtmax at 10 microM by 13% and at 100 microM by 45%; the effects of phenytoin were 5% and 15%, respectively. Thus, ralitoline and phenytoin exert sodium antagonistic effects. Related to the anticonvulsive concentrations seem in rodent brain, the inhibition of voltage-dependent sodium channels, which is primarily the suggested mechanism of action of phenytoin, may contribute to the anticonvulsive activity of ralitoline.

Action Potentials↗
PubMed1987

Investigations on the binding of erythrogenic toxin A of Streptococcus pyogenes on human peripheral blood lymphocytes. I. Light and electron microscopical demonstration of cell surface receptors using colloidal gold-labelled toxin.

Receptors for erythrogenic toxin A (ETA) of Streptococcus pyogenes (strain NY-5) were demonstrated on human peripheral blood lymphocytes by binding of ETA-gold conjugates to the cell surface. The specificity of the binding was proved in control experiments. The dark-red granules observed by light microscopy on unfixed cells were revealed by transmission electron microscopy to be patches of gold particles. By light microscopy on samples from 48 blood donors a mean value of 34 +/- 13% of ETA-receptor bearing lymphocytes was ascertained. The predominant part of the cells exhibited only a weak or moderate labelling. Transmission electron microscopy of prefixed cells revealed an attachment of single gold particles distributed over the whole cell surface. Counts of gold particles on serial sections yielded depending on prefixation values of 50-600 receptors/cell (1% glutaraldehyde) and 1000-7000 receptors/cell (0.26% glutaraldehyde), respectively. ETA cloned in Streptococcus sanguis as well as the toxoid of ETA exhibited a comparable binding as ETA (NY-5).

Bacterial Proteins↗
PubMed1987

Activation of human prorenin by neutrophil elastase.

Although about 90% of human renin circulates as inactive prorenin, the mechanism of prorenin activation in vivo is not known. We found that human polymorphonuclear leukocytes (PMN) activate prorenin at a neutral pH. Prorenin was partially purified from human amniotic fluid, and its activation was measured by the release of angiotensin I from sheep angiotensinogen. In control experiments, thermolysin was the standard activator. PMN cells were separated from blood and, after N2 cavitation or degranulation by cytochalasin, were fractionated by differential centrifugation. Elastase and cathepsin G activities were determined with synthetic fluorescent substrates. The activators of prorenin concentrated in the azurophil granules were released by Triton; most of the activation was due to elastase. Elastase, purified from human PMN, activated prorenin completely. The activation by the granular fraction was inhibited 77% by a specific elastase inhibitor in the presence of a detergent, but only 22% by a cathepsin G inhibitor. After inhibition of elastase, the residual activity was inhibited by diisopropylfluorophosphate; thus, it was due to a serine protease(s) such as cathepsin G. We suggest that human renin fully activated by elastase may still contain an N-terminal pentapeptide fragment of the propeptide.

Amniotic Fluid↗
PubMed1987

Treatment of relapsing acute lymphoblastic leukemia in childhood. I. Experiences with 82 first bone marrow and 17 isolated central nervous system relapses observed 1968-1980.

Of 99 patients with acute lymphoblastic leukemia in first bone marrow or isolated CNS relapse seen between 1968 and 1980, 48 were treated without standardized protocol and 51 according to a relapse protocol. Of 16 patients with bone marrow relapse after cessation of the initial treatment 6 survived 8 1/2 years or more, of 66 with bone marrow relapse while on therapy only 4 survived. All of the latter were low risk patients with an initial WBC of less than 20 x 10(9)/l and no enlargement of the mediastinum. All of the 17 patients with isolated CNS relapse died. The relapse protocols used probably improved the chances of children with first bone marrow but not of those with isolated CNS relapse.

Antineoplastic Combined Chemotherapy Protocols↗