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Biomedical subjects

B Wagner

Publications and source records attributed to B Wagner.

At least 181 records · Page 10Linked to original sources

Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group.

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.

Adult↗

Effect of ritanserin, a 5-hydroxytryptamine2-receptor antagonist, on platelet function and thrombin generation at the site of plug formation in vivo.

To investigate the role of serotonin in platelet plug formation we studied, in eight healthy volunteers, the effect of ritanserin (a 5-hydroxytryptamine2-receptor antagonist) on the platelet release reaction (represented by beta-thromboglobulin release) platelet prostaglandin metabolism (represented by thromboxane B2 formation), and thrombin generation (represented by fibrinopeptide A formation) in the microvasculature. After administration of ritanserin lower amounts of thromboxane B1 were generated in the initial stages of plug formation, suggesting an inhibitory effect on the platelet prostaglandin metabolism. Similar amounts of beta-thromboglobulin were released after the administration of ritanserin compared with placebo, indicating a minor effect of ritanserin on the release reaction. Reduction of thrombin formation by ritanserin in the later stages of hemostasis suggested an inhibitory effect of this substance on the procoagulatory activity of platelets or endothelial cells. This could be attributable to interference with the formation or function of coagulation factor complexes on cell surfaces, or it could be the consequence of a reduction of the platelet activity.

Adult↗

Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF.

In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA2 (measured as thromboxane B2, TxB2) and beta-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI2 (measured as 6-keto-prostaglandin F1 alpha) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA2 and beta-TG concentration in the microvasculature. No effect was seen on PGI2 production, thereby excluding a major effect on vascular prostaglandin metabolism.

6-Ketoprostaglandin F1 alpha↗

[The diagnostic value of MR tomography following gadolinium-DTPA compared to computed tomography in bladder tumors].

In a prospective study, 58 patients with carcinomas of the bladder were examined by CT and MRI; in 48, gadolinium-DTPA was administered intravenously. MRI provided exact staging in 89%, compared with 80% with CT. There was 13% over-staging with CT and 11% with MRI. MRI, unlike CT did not result in any under-staging. In 36 patients a quotient could be calculated from the signal intensity of the tumour and surrounding soft tissues both before and after the intravenous contrast medium and the increased quotient after contrast administration could be estimated. There was a significant increase in the tumour/muscle quotient with a mean of 72 +/- 22% (minimum 43%, maximum 153%), corresponding to a marked increase of the signal from the tumour when compared with the pre-contrast images. This had the following advantages compared with CT: accurate differentiation between superficial and intramural spread. MRI was better than CT at demonstrating tumours in the roof of the bladder and at the trigone.

Adult↗

Down-regulation and inactivation of neutral endopeptidase 24.11 (enkephalinase) in human neutrophils.

Neutral endopeptidase (EC 3.4.24.11, NEP) is an integral membrane protein of human neutrophils. NEP is identical with the common acute lymphoblastic leukemia antigen (CALLA) of leukemic cells. The expression of NEP on the surface of neutrophils is down-regulated by endocytosis which can be induced by phorbol 12-myristate 13-acetate (PMA) at 37 degrees C. The activity of the enzyme on the surface of intact cells decreases by 76% within 5 min. The activity can be recovered, however, if the cells are lysed within 5 min of the endocytosis. After 30 min, only 32% of the NEP activity is present in the neutrophil lysates. The loss of activity is presumably due to proteolytic inactivation. Diacylglycerol and monoclonal antibody to CALLA/NEP also induce internalization of NEP. PMA induces endocytosis even at 4 degrees C, but NEP is not inactivated at that temperature. The disappearance of NEP activity after adding PMA was inhibited by various agents. Among the most active were the phospholipase inhibitor 4-bromophenacyl bromide and a combination of the serine protease and cathepsin inhibitors, diisopropylfluorophosphate and N-ethylmaleimide. The employment of fluorescent monoclonal antibody confirmed the down-regulation and internalization of NEP antigen on the neutrophils. Since NEP inactivates chemotactic peptides and thereby affects chemotaxis of neutrophils (Painter, R. G., Dukes, R., Sullivan, J., Carter, R., Erdös, E. G., and Johnson, A. R. (1988) J. Biol. Chem. 263, 9456-9461), the down-regulation of NEP activity on the cell membrane may modulate the function of these cells in inflammation.

Antibodies, Monoclonal↗

Effect of Ca2+ entry blockers on myosin light-chain kinase and protein kinase C.

Thirteen Ca2+ entry blockers were compared with respect to their inhibitory effects on the activity of smooth muscle myosin light-chain kinase and smooth muscle protein kinase C, and the Ca2+-induced contraction of basilar artery rings. Comparison of the IC50 values obtained for these compounds, suggests that with the exception of ferdiline inhibition of the enzymes does not contribute to vascular smooth muscle relaxation.

Animals↗

Immunoelectron microscopy of Bacillus subtilis cells secreting human interferon alpha 1 or staphylokinase.

Post-embedding labelling techniques with colloidal gold-IgG or -protein A complexes were used to determine the subcellular location of IFN alpha 1 and staphylokinase secreted from Bacillus subtilis GB500 cells. Both proteins were present in the cytoplasma and the cell envelope pointing to a posttranslational mode of translocation across the cytoplasmic membrane. 5- to 10-fold higher concentrations of gold particles per 0.1 micron 2 were found on the cell envelope and clustering was observed suggesting preferential regions for secretion sites. Several control experiments ensured the specificity of the labelling data.

Bacillus subtilis↗

Effects of progesterone and oestradiol-17 beta on 17 beta-ol-dehydrogenase activity in stromal cells of human endometrium under in-vitro conditions.

A 17 beta-ol-dehydrogenase activity could be demonstrated in fibroblast monolayer cell cultures of proliferative human endometrium. After 24 h incubation 100 nCi [6,7-3H]oestradiol-17 beta was completely oxidized to oestrone. Progesterone was not able to enhance the metabolizing velocity. In contrast, progesterone incubation revealed a decreasing oxidation rate with increasing molarity. Histological changes after transformation of the endometrium are discussed to explain in-vivo results showing an increased 17 beta-ol-dehydrogenase activity in the secretory phase of the cycle.

17-Hydroxysteroid Dehydrogenases↗

Development and validation of a radioimmunoassay for serum melatonin.

A radioimmunoassay using N-[3-(4-hydroxy-3-[4-hydroxy-3- [125I]iodophenylpropionyl)]-5-methoxytryptamine as tracer for determination of melatonin in the serum of different species is described. Melatonin antisera were raised in rabbits by immunization with a bovine serum albumin conjugate of N-[3-(2-aminoethyl)-5-methoxy indole] hemisuccinamide. A single high affinity, specific antiserum was obtained. In contrast to previous studies, the tracer was synthesised in one step in the absence of water, giving an excellent yield of highly pure product. No chromatographic purification step was needed. Polyethylene glycol in combination with goat antirabbit immunoglobulins was used to separate bound and unbound tracer. Sera were delipidized with Lipoclean prior the extraction of melatonin with diethyl ether. This sample preparation allows the determination of melatonin in the presence of widely varying amounts of lipids in human, rat and hamster serum. Using this extraction procedure, the sensitivity of the radioimmunoassay was approximately 1 ng/l of serum. Dilutions of sera and of synthetic melatonin gave the same parallel response in the radioimmunoassay. High performance liquid chromatography analysis of a serum extract showed only one immunoreactive peak co-eluting with synthetic melatonin. Characteristic diurnal rhythms of melatonin were observed in all species. All assay components including standards and serum controls are stable for at least 1 year at 4 degrees C, thus facilitating the determination of melatonin in a routine laboratory.

5-Methoxytryptamine↗

Inhibitory effect of neurotensin on pentagastrin-stimulated gastric acid secretion in pylorus-ligated rats.

Neurotensin is a known inhibitor of gastrin-stimulated acid secretion in dogs and humans. In order to study the dose-related effect of neurotensin, we prepared pentobarbital-anesthetized rats by pyloric ligation and collected gastric secretions one hour after injection of saline (Basal), pentagastrin, 6 micrograms/Kg subcutaneously (PG Alone), or pentagastrin plus neurotensin by tail vein injection (PG + NT). Acid output was calculated from the volume and pH of the samples, which correlated well with the output determined by titration with 0.02 N NaOH (r = 0.92). Basal output was 36 +/- 4 muEq/hr; stimulated output (PG Alone) was 64 +/- 5 muEq/hr, and output after PG + NT, 250 pmol/Kg, was 33 +/- 3 muEq/hr (p less than 0.001). The effect of neurotensin was dose-related over a range from 125 to 500 pmol/Kg. This technique may be useful in the biological evaluation of neurotensin-related peptides.

Animals↗