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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 343 records · Page 19Linked to original sources
PubMed1991

[Profibrinolytic activity of recombinant hirudin?].

Recombinant hirudin (rH, CGP 39393) is a potent thrombin inhibitor. In addition to its anticoagulant effect, we investigated its profibrinolytic activity in vitro and ex vivo. The fibrinolytic activity of the euglobulin fraction of 15 normal plasmas with or without urokinase was tested in a fibrin plate assay both before and after addition of rH. The same cycle was repeated in 8 plasmas with heparin instead of rH. For the ex vivo evaluation 12 healthy volunteers received 0.1-0.3 mg/kg/h rH for 6 h. Blood samples were drawn at 0 h, 6 h, 12 h and 24 h and various fibrinolytic parameters were assayed. In the presence of rH or heparin a slightly stronger fibrinolytic effect was observed, measured as fibrin plate lysis activity, both when rH was added to plasma in vitro and when it was administered intravenously. However, this may be explained by the specific anticoagulant action of rH and heparin in the dynamic equilibrium of fibrinolysis and clotting in the test system. Moreover, under rH treatment the observed changes in the various fibrinolytic parameters could not be differentiated from the normal circadian rhythm of these proteins. There was no convincing evidence to indicate enhancement of plasma fibrinolytic activity by recombinant hirudin.

Adult↗
PubMed1991

Role of von Willebrand factor associated to extracellular matrices in platelet adhesion.

The respective role of plasmatic and endothelial extracellular matrix (ECM)-associated von Willebrand factor (vWF) in platelet adhesion was investigated at a high shear rate using a parallel-plate perfusion chamber. Incubation of the endothelial ECM with a monoclonal antibody (MoAb) to vWF, which specifically blocks vWF binding to platelet GP Ib (MoAb 322), inhibited 45% of platelet adhesion. Complete inhibition was achieved by incubating both plasma and endothelial ECM with MoAb 322 at concentrations that blocked only about 50% of adhesion when added separately. The effect of ECM-associated vWF was further demonstrated when a fibroblastic ECM, normally devoid of vWF, was coated with purified plasmatic vWF. Matrix associated-vWF was able to significantly enhance platelet adhesion in both the presence and the absence of plasmatic vWF. In contrast, this effect was not seen on endothelial ECM. Binding of exogenous vWF to the ECM was specific and dose dependent, reached the same value (500 ng/cm2) on both fibroblastic ECM and endothelial ECM, but exhibited a threefold-lower apparent dissociation constant (KD) on fibroblastic than on endothelial ECM. Our studies suggest that vWF deposited by endothelial cells in the ECM may be the most active form in platelet adhesion, whereas plasmatic vWF may only play a secondary role.

Cells, Cultured↗
PubMed1991

Long-term marrow cultures: human and murine systems.

The intramedullary control of marrow cell production has been a difficult area to approach experimentally. The introduction by Dr. Dexter and colleagues of long-term stromal dependent culture systems for murine marrow and the adaptation of these systems to human marrow growth have allowed for in-vitro studies of stromal dependent hemopoiesis. Despite some controversy in this area, most studies appear to show that adherent murine or human stromal cells are capable of producing a relatively large number of hemopoietic growth factors including G-CSF, GM-CSF, CSF-1, IL-6 and, at least by PCR analysis, IL-3. Other work indicates that the most primitive hemopoietic cells which appear to be multifactor responsive adhere directly to these stromal cells presumably through mediation of various adherence proteins. An early acting, multilineage factor termed hemolymphopoietic growth factor-1 (HLGF-1) has been isolated from a murine stromal cell line and may be identical to the recently described ligand for the c-kit receptor. This may represent an important early survival/maintenance factor for stem cells in this system. Studies on primitive stem cells, especially the high proliferative potential colony forming cell (HPP-CFC), indicate that they are responsive to varying combinations of growth factors and that with increasing numbers of growth factors, as studied in serum-free systems, decreasing concentrations of the factors may be biologically active. These observations altogether suggest that intramedullary hemopoiesis may be regulated by the positioning of early multifactor responsive stem cells via adherent proteins in juxtaposition to synergistically acting combinations of growth factors attached to stromal cell surfaces or the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

140-MDa plasmids of Escherichia coli and Shigella flexneri 5 do not influence phagocytosis.

Enteroinvasive Escherichia coli (EIEC) and Shigella flexneri possessing a 140-megadalton (MDa) plasmid are capable of invading intestinal epithelial cells and causing dysentery. To determine if this plasmid affected phagocytosis of the organisms by leukocytes, we studied the in vitro phagocytosis of isogenic pairs of EIEC and S. flexneri 5 which differed only in the presence or absence of the 140-MDa plasmid. In addition five EIEC strains containing 140-MDa plasmids as well as one non-enteroinvasive E. coli strain possessing a 120-MDa plasmid were studied. The 140-MDa plasmid did not affect phagocytosis of these bacteria by normal human blood neutrophils or monocytes.

Escherichia coli↗
PubMed1991

von Willebrand factor: structure and function.

Von Willebrand factor (vWF) is an adhesive, multimeric glycoprotein present in plasma, platelets, and subendothelium, which has two main functions: (1) it serves as a carrier for factor VIII and (2) it plays a crucial role in platelet adhesion to subendothelium, acting as a "bridge" between platelet membrane glycoprotein (GP) Ib and GP IIb/IIIa and subendothelial components such as collagen and heparin. vWF is involved at high shear rates in the initial contact of platelets with the subendothelium, in their subsequent spreading, and in thrombus formation. The three pools of vWF (plasma, platelets, and subendothelium) are necessary for optimal adhesion. Specific fragments of vWF involved in binding to platelets, collagen, heparin, and factor VIII have been mapped by using a series of proteases and well-characterized monoclonal antibodies to distinct epitopes of vWF. Several groups, including ours, have identified at least eight functional domains on the 270-kd subunit that consists of 2,050 amino acids. The importance of the binding domains to GP Ib and to collagen is illustrated by the role of vWF fragment SpIII (amino acids 1 through 1,365) in promoting platelet adhesion to collagen. The role of the vWF-GP Ib axis and of the vWF-GP IIb/IIIa axis in platelet-vessel wall interactions has been demonstrated through the study of patients, monoclonal antibodies, recombinant fragments, and synthetic peptides. We have recently expressed fragments of vWF complementary DNA in Escherichia coli. One of these recombinant fragments, which spans amino acids 449 through 730, binds to platelets in the presence of ristocetin, to collagen, and to heparin and has the property of inhibiting ristocetin-induced platelet agglutination. The second fragment, which spans amino acids 914 through 1,364, binds to collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1991

Carrier detection and prenatal diagnosis in 98 families of haemophilia A by linkage analysis and direct detection of mutations.

489 individuals from 98 families with a haemophilia A member were studied with restriction fragment length polymorphisms (RFLPs) for carrier detection and prenatal diagnosis. Five intragenic polymorphisms revealed with the restriction enzymes BclI, XbaI, BglI, HindIII and AlwNI and one extragenic multiallelic polymorphism (St14) at the DXS52 locus were used. The combination of the five intragenic polymorphisms did not add significantly more information than just the BclI and XbaI polymorphisms because of strong linkage disequilibrium. The sequences surrounding the intronic restriction sites of the BclI and XbaI RFLPs are known so they can be rapidly analysed using the polymerase chain reaction (PCR). 68.6% of the women were heterozygous for either the BclI or XbaI RFLP and this heterozygosity rate increased to 98.6% when the St14 extragenic polymorphism was included. Linkage analysis using these RFLPs led to the classification of over 90% of the women as carriers or normal and 98.6% of the carriers were heterozygous. Prenatal diagnosis was successful in the 16 foetuses tested and all could be classified as carrier, normal or haemophiliac. Five TaqI restriction sites in the coding region of the factor VIII gene can detect a C to T transition that results in an in-frame stop codon. These five sites were amplified by PCR in 119 haemophiliacs and tested for an abnormal TaqI restriction pattern. A stop codon was found in three haemophiliacs at exons 18, 22 and 24. The same analysis revealed three deletions, two involving the last exon 26 and one exons 23-26.

Alleles↗
PubMed1991

von Willebrand factor and platelet interactions with the vessel wall.

von Willebrand factor (vWF) is a multimeric glycoprotein which has a dual role in haemostasis, functioning as carrier protein for Factor VIII and mediating platelet adhesion to exposed subendothelium (SE). vWF interacts with components of the SE such as collagen and heparin-like glycosaminoglycans as well as with two platelet membrane receptors: glycoprotein (GP) Ib and GPIIb/IIIa. These multiple binding functions explain its definition as an adhesive protein. vWF promotes platelet adhesion at the high shear rates which correspond to the rheologic conditions of the microcirculation or of narrowed arterial vessels. The role of the vWF-GPIb interaction in platelet adhesion is well known; that of the vWF-GPIIb/IIIa interaction has been more recently demonstrated through the use of monoclonal antibodies (MAbs) or synthetic peptides blocking vWF-binding to GPIIb/IIIa. In addition, perfusion studies in native, non-anticoagulated blood emphasize the concept that vWF is also essential for thrombus formation at high shear stress. Thus, vWF fragments, synthetic peptides or MAbs blocking the functional domains of vWF represent potential therapeutic strategies to prevent the development of thrombosis.

Blood Coagulation↗
PubMed1991

Functional assay of protein S in 70 patients with congenital and acquired disorders.

A functional assay for the selective measurement of the active form of protein S in plasma, based on the prolongation of an APTT, was previously developed. This assay is sensitive, reproducible and specific, not affected by other clotting factors including FVIII. This method was applied to the measurement of protein S activity in congenital and acquired disorders. Results of protein S activity were compared to those of total and free antigen measured by ELISA. In 30 controls, there was an excellent correlation between protein S activity and free antigen. In patients with inflammatory disease, protein S activity and free antigen were normal, despite high levels of both C4b-binding protein and total protein S antigen. In dicoumarol-treated patients, protein S activity was lower than free antigen due to the presence of acarboxylated forms. Surprisingly, in liver cirrhosis, free antigen was only slightly decreased whereas protein S activity was significantly reduced. In 23 patients with congenital deficiency, protein S activity was consistently decreased, from less than 5% to 60% and showed good correlation with the free antigen. This functional assay allows the rapid diagnosis of congenital or acquired deficiency of protein S.

Adult↗
PubMed1991

Motivating factors in a student's choice of nursing as a career.

Motivation factors in a student's choice of nursing as a career were the focus of this study. There was a three-fold purpose: definition of nursing, reasons for choosing nursing, and who/what influenced their choice. A questionnaire was developed to collect data from a random national sample of nine BSN and 11 ADN NLN-accredited schools. The five most frequent responses to the question "What does nursing mean to you?" were: caring, personal growth, illness focus, professionalism, and job security. The most frequently reported reasons for choosing nursing were: nurturance, emotional needs, employment opportunities, financial benefits, and interest in science. Practicing nurses were identified most frequently as influencing students' image of nursing/choice of nursing. Nursing continues to be perceived as a caring profession as well as one that offers many personal benefits.

Adult↗
PubMed1991

[Anomalous origin of the left coronary artery from the pulmonary artery (Bland-White-Garland syndrome) in a 29-year-old male with absolute tachyarrhythmia].

We report on a man without any symptoms until the age of 29 years when a ventricular tachyarrhythmia occurred for the first time. There were electrocardiographic signs of a previous myocardial infarction of the anterior wall, but there had not even been any episode of angina pectoris. The cause was the anomalous origin of the left coronary artery from the pulmonary trunk (Bland-White-Garland syndrome). Therapy consisted of ligation of the left coronary artery and the implantation of an aortocoronary vein graft to the left coronary artery in order to reinstall a two-coronary system. Diagnosis is easily made by coronary angiography. At a 3-year follow-up there was an increase of the ejection fraction/cardiac output, a stable sinus rhythm, and an improved physical endurance.

Adult↗
PubMed1991

[Evaluation of thyroid gland scintigraphy and thyroid gland ultrasonography from the surgical viewpoint].

The results of thyroid ultrasound and scanning on 251 patients have been reviewed in regard of the postoperative histological findings. Both procedures (thyroid ultrasound and scanning) cannot predict the histology. But with ultrasound adenomas of the thyroid for example could be localized in 93%, with isotope scanning only in 74%. Merely 2% of cold nodules with decreased or mixed sonographic pattern have been malignant. Ultrasonography is extremely helpful for the surgeon in his operative planning.

Adenocarcinoma↗
PubMed1991

Cloning, sequencing, and expression of two Xenopus laevis c-ets-2 protooncogenes.

In a general approach to identify genes important in the control of genetic expression during development of Xenopus laevis, two complementary DNAs corresponding to two different c-ets-2 genes were cloned and sequenced. One of these complementary DNAs appears to be almost full length. The two variant genes differ in their overlapping sequences by 87 nucleotide substitutions, leading to 17 amino acid modifications in the proteins, 8 of them being conservative. All but one of these changes map outside of the 142 COOH-terminal residues, a region critical for nuclear localization and DNA binding in the ets proteins. Features potentially important for the biological activity of the gene products are conserved. Two transcripts (3.2 and 1.7 kilobases) with maternal characteristics are detected at a constant level from stages II/III of oogenesis to stage 10 of embryogenesis. They later decline to hardly detectable levels at stages 30-40. Variable amounts of the same transcripts are observed in many adult tissues. All of these characteristics support the idea that the ets-2 gene products play an important role during embryogenesis, as well as in adult life. Indeed, they act as ubiquitous transcriptional activators, as recently demonstrated by several investigators (C. V. Gunther, J. A. Nye, R. S. Bryner, and B. J. Graves, Genes & Dev., 4: 667-679, 1990; R. Bosselut, J.F. Duvall, A. Gegonne, M. Bailly, A. Hemar, J. Brady, and J. Ghysdael, EMBO J., 9: 3137-3144, 1990; R. Wasylyk, C. Wasylyk, P. Florès, A. Bègue, D. Leprince, and D. Stéhelin, Nature (Lond.), 346: 191-193, 1990).

Amino Acid Sequence↗
PubMed1991

Do public cholesterol screenings really screen?

Two hospital-sponsored cholesterol-screening programs were evaluated to assess whether they detected individuals with undiagnosed high blood cholesterol. Surveys asking about prior testing, knowledge of cholesterol level, and participant characteristics were examined to test screening utilization. In both screenings 54% of participants reported having prior cholesterol testing, only 56% of whom knew their cholesterol level. Of previously untested participants, 8% had high blood cholesterol levels and 13% had borderline levels. Only 65% of participants with a personal or family history of heart attack were aware of their cholesterol level. To attract individuals without prior testing, screening planners should consider locations (eg, worksites and schools) and methods (eg, weekend screenings) to target underrepresented groups in community-wide cholesterol screenings. We encourage an increased emphasis on individualized exit education for participants, especially those who know their cholesterol level or have multiple risk factors for vascular disease. Physicians planning public screenings can utilize this data to develop parameters for referrals from the screenings.

Adult↗