Search PubMed⌕ Search

Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 451 records · Page 25Linked to original sources

[Cervix priming in induced abortion in the 1st trimester using intracervical administration of sulprostone gel].

In a prospective, randomised study 40 primigravidae were treated intracervically with 0.05 mg or 0.1 mg Sulprostone-Tylose gel in order to soften the cervix prior to first trimester termination of pregnancy. Curettage was performed on the average 7.5 hours after prostaglandin administration. For objective demonstration of the priming effect, the force required for dilatation of the cervical canal was measured in Newtons by a special tonometer before prostaglandin application and before operation. The maximal dilatability with a force of 10 N, the increase in dilatability after local PG application, and the patency of the cervix were measured. The occurrence of PG-induced lower abdominal pain associated with contractions was analysed with regard to the number of episodes at pain, their timing and the required amount of analgesics. A modified visual analogue scale was used to evaluate the subjective pain experience. The abortive effect of 0.1 mg Sulprostone was found to be more efficient than the 0.05 mg dose. There was no statistical significant difference between the two doses, however, for the priming effect detectable with the tonometer. The subjective experience of pain, use of analgesics and the frequency of gastrointestinal side effects were significantly higher with 0.1 mg than with 0.05 mg Sulprostone. The visual analogue scale allows the patient to quantify, at least to some extent, her experience of pain, and enables a differentiated analgetic therapy. Because of its effectiveness and low rate of side effects, the intracervical application of 0.05 mg Sulprostone gel promises to be an advantageous alternative to other methods of cervical priming.

Abortifacient Agents↗

Diagnostic potential of CT in neurotological disorders.

The reliability of a neurotological evaluation in differentiating labyrinthine (end organ) lesions from retrolabyrinthine lesions has been well established. The purpose of this communication is to determine the diagnostic potential of computed tomography (CT) in patients suspected of having retrolabyrinthine lesions on the basis of their neurotological evaluations. Our study indicates that the validity of central vestibular and audiometric signs can be best substantiated with CT. The anatomy of neurovascular bundles within the internal auditory canal and cerebellopontine cistern can be readily visualized and identified by CT pneumocisternomeatography. By obtaining appropriate thin CT sections not only can very small lesions be identified but their anatomic locations can also be accurately established. CT pneumocisternomeatography is the method of choice to diagnose an intracanalicular acoustic neuroma. An unusually large vascular loop of the internal auditory canal may be responsible for sensorineural hearing loss and tinnitus in some patients.

Adolescent↗

Abnormality of glycoprotein Ib in two cases of "pseudo"-von Willebrand's disease.

Two unrelated patients with "pseudo" ("platelet-type")-von Willebrand's disease (vWD) are described demonstrating thrombocytopenia with a prolonged bleeding time, ristocetin-induced platelet aggregation at low stimulus concentrations, decreased levels of ristocetin-cofactor activity (vWF:RCo), slight cryoprecipitate-induced platelet aggregation in the absence of ristocetin, and a lack of the high molecular weight factor VIII-von Willebrand factor (FVIII/vWF) multimers in plasma. Isolated washed patient platelets bound more FVIII/vWF at high (1 and 0.75 mg/ml) and low (0.5 and 0.25 mg/ml) ristocetin concentrations than control platelets. Fresh or paraformaldehyde-fixed washed platelets from these patients also bound more specific monoclonal antibody to glycoprotein Ib (25,000 binding sites per cell) than normal platelets (15,000 +/- 3,300 binding sites per cell). Results obtained in control patients with thrombocytopenia and increased platelet size (May-Hegglin anomaly and vWD type IIB) excluded a nonspecific increase of glycoprotein Ib in the platelets of the patients with pseudo-vWD. These data indicate that in pseudo-vWD, the primary abnormality lies in the platelet and is related to a quantitative and/or qualitative anomaly of platelet membrane glycoprotein Ib.

Factor VIII↗

Eccentric localization of von Willebrand factor in an internal structure of platelet alpha-granule resembling that of Weibel-Palade bodies.

Immunogold staining was used to study the ultrastructural distribution of von Willebrand factor (vWF) in unstimulated platelets. vWF was detected in the alpha-granules with a specific eccentric distribution pattern opposite the nucleoids. Similar findings were obtained with a polyclonal antibody or a pool of monoclonal antibodies to human vWF. This labeling coincided with the presence of tubular structures located at the periphery of the alpha-granules. These structures were better visualized on platelets treated for standard electron microscopy: they formed a group of one to four tubules ranging from 200 A to 250 A in diameter. They closely resembled the internal tubular structures found in Weibel-Palade bodies, which are the storage organelles of vWF in endothelial cells.

Antibodies, Monoclonal↗

Antithrombin Milano: a new variant with monomeric and dimeric inactive antithrombin III.

A qualitative defect of antithrombin III (AT III) has been demonstrated over three generations in eight members of an Italian family by the discrepancy between a normal amount of antigen and decreased antithrombin and anti-Xa activity in the presence or in the absence of heparin. By two-dimensional immunoelectrophoresis in the absence of heparin, two peaks of AT III were present in all patients' plasma. AT III was purified from normal and propositus plasma by sulfate dextran precipitation followed by heparin affinity chromatography. The elution profile of the patient's AT III was abnormal and allowed the separation of two populations of AT III, normal and abnormal. The first fraction (normal AT III) contained AT III activity, migrated as a single peak by two-dimensional immunoelectrophoresis and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), demonstrated a single band with a molecular weight (mol wt) identical to that of normal AT III (60,000). Conversely, the last fraction, devoid of AT III activity, migrated as a single abnormal peak by two-dimensional immunoelectrophoresis in the absence of heparin. By SDS-PAGE, two bands were observed: one with a mol wt of 60,000 and a second one with a mol wt of 120,000. Western blots clearly demonstrated cross-reactivity of the 120,000 and 60,000 mol wt bands with monospecific antisera to human AT III. Reduction of the 120,000 mol wt band converted it to a single 60,000 mol wt band, suggesting the presence of an abnormal dimeric form of AT III. The name AT III Milano is proposed for this new variant.

Adult↗

A new method for the estimation of protein C by ELISA.

A new solid phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of human protein C antigen. Anti-protein C F(ab')2 fragments were adsorbed to polystyrene plates. The binding of serial dilutions of control or test plasma, containing protein C, was detected by incubation with peroxidase-labeled anti-protein. C-IgG followed by the addition of hydrogen peroxyde and 0-phenylenediamine. This ELISA is specific, sensitive (detection limit: 0.02%) and accurate (variation coefficient: 3 to 10%). When results are compared to those obtained by the Laurell technique (electroimmunodiffusion, EID), the correlation coefficient is 0.95 in all tested plasmas. Protein C antigen was measured by ELISA and EID in plasma from 40 controls, 14 patients with congenital protein C deficiency, 15 patients with liver cirrhosis and 40 dicoumarol-treated cases. In normal plasma, protein C ranged from 70 to 126%. In congenital deficiency, protein C was between 35 and 58% in 13 cases and 9% in one of them. In patients with liver cirrhosis and dicoumarol-treated cases, levels of protein C antigen were compared to those of other vitamin K dependent factors, i.e. Factors II and IX measured by EID and Factor X assayed by EID and ELISA. In liver cirrhosis, the amount of protein C was significantly lower than that of Factors II, IX and X. In short-term and long-term dicoumarol-treated patients, the highest correlation (r = 0.72) was observed between protein C and Factor X levels. In the plasma of patients undergoing oral anticoagulant therapy, protein C decreased more rapidly than Factors X or II and migrated in presence of calcium as a double peak, one with a normal mobility and one more anodal corresponding to the non carboxylated form of protein C.

Antigens↗

Von Willebrand factor has more than one binding site for platelets.

By the use of a series of monoclonal antibodies against platelet membrane glycoproteins (GP) and the von Willebrand factor (vWF), it is shown that thrombin-induced binding to GP IIb/IIIa involves a different site on vWF from ristocetin-induced binding to GP Ib.

Antibodies, Monoclonal↗

Evidence that three adhesive proteins interact with a common recognition site on activated platelets.

Synthetic peptides corresponding to the extreme COOH terminus of the gamma chain of fibrinogen gamma 400-411, (400)HHLGGAKQAGDV(411), have been used to analyze recognition specificities of the platelet-binding sites for fibrinogen, fibronectin, and von Willebrand factor. gamma 403-411 did not inhibit 125I-fibrinogen binding to platelets. In contrast, gamma 402-411 produced dose-dependent inhibition of fibrinogen binding to ADP and thrombin-stimulated living or fixed cells and was a competitive antagonist. Inhibitory activity was not modified by addition of one (gamma 401-411) or two (gamma 400-411) histidinyl residues to the NH2 terminus, but peptides with a trifluoroacetyl group on the epsilon-amino group of lysine 406 were inactive. 125I-Fibronectin and 125I-von Willebrand factor binding to thrombin-stimulated living or fixed cells was inhibited in the same dose range by the same set of peptides which inhibited fibrinogen binding and not by gamma 403-411 or trifluoroacetate-blocked peptides. The capacity of the peptides to inhibit binding to cells with an expressed receptor, i.e. fixed cells, excludes an effect on receptor induction. Thus, these results suggest that the three adhesive glycoproteins share a common site on thrombin-activated platelets, and a 10-amino acid peptide, corresponding to gamma 402-411, defines the recognition specificity of this site.

Blood Coagulation Factors↗

Purification and partial amino acid sequence of the chloroplast cytochrome b-559.

The hydrophobic cytochrome b-559, purified from unstacked, ethanol-washed spinach thylakoid membranes, using extraction with 2% Triton X-100 in 4 M urea and three chromatographic steps in the presence of protease inhibitors, has a dominant band on sodium dodecyl sulfate-urea gels corresponding to Mr = 10,000. The yield of this preparation is 30-50% (5-10 mg) starting with 600 mg of chlorophyll. The heme content yields a calculated molecular weight of no more than 17,500/heme, and perhaps somewhat smaller after correction for impurities. The Mr = 10,000 band is stained by the tetramethylbenzidine-H2O2 heme reagent on lithium dodecyl sulfate gels run at 0 degrees C. The Mr = 10,000 protein, further separated by high performance liquid chromatography, contains a unique NH2 terminus that is not blocked, and the amino acid sequence for the first 27 residues is NH2-Ser-Gly-Ser-Thr-Gly-Glu-Arg-Ser-Phe-Ala-Asp-Ile-Ile-Thr-Ser-Ile-Arg-Tyr-Trp -Val-Ile-X-Ser-Ile-Thr-Ile-Pro. . . COOH. Approximately 55% of the amino acids are hydrophobic, based on amino acid analysis of the Mr = 10,000 peptide, which also indicated the presence of at least one histidine. Only one cytochrome b-559 component could be identified, whose yield indicated that it arises from a single b-559 protein in chloroplasts corresponding to the in situ high potential cytochrome of the chloroplast photosystem II.

Amino Acid Sequence↗

Hybridoma antibodies to human von Willebrand factor. I. Characterization of seven clones.

Twenty-seven stable subclones of seven independent cellular hybrids producing murine monoclonal antibodies to human von Willebrand factor (vWF) have been established. The specificity of the hybridoma antibodies for vWF has been substantiated by a variety of methods including binding to highly purified vWF, absence of binding to plasma or cryoprecipitate from severe von Willebrand's disease, binding to different size multimers in normal plasma, and binding to low molecular weight multimers in type IIA von Willebrand's disease plasma. Monoclonality of the hybridoma derived antibodies has been sought by repeated cloning at limiting dilutions. All seven specificities of hybridoma antibodies cross-react to a variable degree with porcine vWF and all but one with bovine vWF, indicating that they bind to structural loci that are relatively though not identically conserved between species. Hybridoma antibodies bind native as well as denatured vWF, suggesting that the epitopes may be determined to a considerable extent by primary structure rather than entirely by tertiary or quaternary conformation. The hybridoma antibodies define precise epitopes in the vWF molecule, extend the horizon of direct analysis of vWF to the intramolecular level, and may be useful in assigning functional loci to parts of the molecule.

Animals↗

Hybridoma antibodies to human von Willebrand factor. II. Relative role of intramolecular loci in mediation of platelet adhesion to the subendothelium.

Hybridoma antibodies specific for seven independent topographical sites were used to characterize von Willebrand factor (vWF) and to relate the epitopes to functional loci required for vWF-mediated adhesion of platelets to subendothelium and ristocetin-induced platelet aggregation. The capacity of antibodies to influence the adhesion of human platelets to rabbit aortic subendothelium was analysed in annular perfusion chambers. At a high shear rate similar to that of the microcirculation, four monoclonal antibodies inhibited adhesion. In contrast, no inhibition was observed at low shear. Only one of the four antibodies that inhibited platelet adhesion also attenuated ristocetin-cofactor activity (VIIIR:RCo). Conversely, one antibody that inhibited VIIIR:RCo had no effect upon platelet adhesion. These data support the hypothesis that the molecular loci involved in the two biological functions of vWF are not identical. When these conclusions are considered within the context of a spatial map of the vWF protein surface developed by competitive displacement analysis, the epitopes related to platelet adhesion appear to be spaced and differ from those involved in ristocetin-induced platelet-platelet interaction.

Animals↗

Incidence of immune responses following 102 infusions of autoplex in 18 hemophilic patients with antibody to factor VIII.

An activated prothrombin complex concentrate (Autoplex) was infused for the treatment of 102 bleeding episodes in 18 hemophilia A patients with antibody to factor VIII who were previously known as high responders. Among 95 bleeding episodes treated with a single infusion of the concentrate [43-107 factor VIII correcting units (FECU)/kg], only 1 anamnestic response was observed. On the contrary, a significant rise in antibody titer occurred following 2 of 4 double (at 8-12 hr interval) and all 3 multiple (over 3-10 days) infusions of Autoplex. The occurrence of immune responses may be explained by the presence of factor VIII coagulant antigen (VIII:CAg) in the 26 batches of Autoplex tested by two-site immunoradiometric assay (10-36 U/vial). The anamnestic response was not correlated to the batch used nor to the amount (0.6-7.8 U/kg/day) of VIII:CAg infused per day. However, exposure to the concentrate over several days appeared to be the major predisposing factor for an immune response.

Adolescent↗