An unusual case of thrombocytopaenia.
Explore the source record for details and available documents.
Anticoagulants↗
Biomedical subjects
D Bowyer
Publications and source records attributed to D Bowyer.
The XMaS beamline at ESRF: instrumental developments and high-resolution diffraction studies.
The beamline, which is situated on a bending magnet at ESRF, comprises a unique combination of instrumentation for high-resolution and magnetic single-crystal diffraction. White-beam operation is possible, as well as focused and unfocused monochromatic modes. In addition to an eleven-axis Huber diffractometer, which facilitates simple operation in both vertical and horizontal scattering geometries, there is an in-vacuum polarization analyser and slit system, mirrors for harmonic rejection, sub 4.2 K and 1 Tesla magnetic field sample environment, plus a diamond phase plate for polarization conditioning. The instrumentation developed specifically for this beamline is described, and its use illustrated by recent scientific results.
Journal Article↗
Magnetism in nickel and synchrotron beam polarization studied by X-ray diffraction.
The ratio of the magnetic to the charge form factors of nickel has been determined by white-beam X-ray diffraction. The measurements were made on the new UK magnetic scattering beamline (XMaS) on a dipole source at the ESRF. The data comprise the three (h,h,0) reflections (4,4,0), (6,6,0) and (8,8,0) and the seven high-order (h,0,0) reflections (6,0,0) to (18,0,0), which doubles the range of wavevectors compared to previous studies. The data have been analysed using Hartree-Fock free-ion wave functions and core electron polarization effects were included. The results support the interpretation of neutron data obtained at lower momentum transfer for the e(g) and t(2g) orbital occupancies. The polarization of the dipole source is deduced to vary from 99.88 to 99.83% between 5 and 15 keV, respectively. This high value makes it an extremely suitable source for studies of ferromagnetism.
Journal Article↗
European Lipoprotein Club: report of the 20th annual conference, Tutzing, 8-11 September 1997.
The year 1997 celebrated the 20th anniversary of the European Lipoprotein Club. Sessions explored topics in the line of classical concepts and forthcoming advances in the field of basic and clinical research on lipoproteins. Participants from 18 European countries attended the conference. Recent Developments in Lipoprotein Research, were reviewed by Thomas Olivecrona (Umea, Sweden), who gave a perspective on lipolysis; and Gerd Assmann (Münster, Germany), who overviewed epidemiological data of the PROCAM study and focused on the biochemical and genetic components of reverse cholesterol transport. Session I, chaired by Katriina Aalto Setälä (Tampere, Finland) and Marten Hofker (Leiden, Netherlands) was dedicated to 'Lipoprotein receptors (old and new)'. Various structural and functional aspects were reported for the newcomers in the ever enriching LDL receptor gene family (VLDLR, LR7/8B, LR11, Megalin, RAP-related proteins). However, a decade of identification of LDL receptors gene defects reveals now that phenocopies of familial hypercholesterolemia may be linked to a third, yet unknown locus. Identification of pathways which clear HDL is underway. Session II, chaired by David Bowyer (Cambridge, United Kingdom) and Richard W James (Geneva, Switzerland), was entitled 'Significance of lipoprotein heterogeneity (metabolic and pathological aspects)'. Factors involved in lipoprotein modification (dense LDL, oxidation), transient production (post prandial, VLDL synthesis) or degradation (complement activation) and controversial hypotheses on their links with atherosclerosis were discussed. Session III on 'Novel methodologies for lipoprotein research' was chaired by Rudolph Poledne (Prague, Czech Republic) and Armin Steinmetz (Marburg, Germany). Simple technologies for routine assessment of lipoprotein metabolism, as well as the most sophisticated ones, to study lipid and free radical exchanges between particles, were presented.
Electrophoresis, Capillary↗
Complement-induced release of monocyte chemotactic protein-1 from human smooth muscle cells. A possible initiating event in atherosclerotic lesion formation.
Increasing evidence suggests that complement activation might represent an important mechanism in early atherogenesis. Thus, complement components, in particular the membrane attack complex (MAC) C5b-9(m), have been isolated from human atherosclerotic lesions. Furthermore, complement activation is known to occur in atherosclerotic lesions induced in experimental animals, and the severity of cholesterol-induced plaques is markedly reduced in complement-deficient animals. During atherogenesis monocytes are recruited into the arterial wall, and a potent chemoattractant for monocytes, monocyte chemotactic protein-1 (MCP-1), is expressed by vascular smooth muscle cells (SMCs). We hypothesized that generation of MACs on SMCs during the activation of complement might lead to the release of MCP-1 and hence to monocyte recruitment. In this study, MACs were generated on human SMCs in vitro by sequential addition of the purified complement components C5b6, C7, C8, and C9. This supernatant of the culture was chemotactic for freshly isolated peripheral blood monocytes in a modified Boyden chamber. The chemotactic activity of the supernatant was abolished by anti-MCP-1 blocking antibodies but not by an isotype-matched antibody against an irrelevant antigen. The release of chemotactic activity was dependent on the dose of MAC formed on SMCs and was demonstrated within 10 minutes of exposure of the cells. The data support the hypothesis that complement-mediated release of MCP-1 from SMCs might be important in the recruitment of monocytes into the developing atherosclerotic lesion and could be an important initiating event in atherogenesis.
Arteriosclerosis↗
Topography of apolipoprotein B in subcellular fractions of rabbit liver probed with a panel of monoclonal antibodies.
We have used a panel of anti-rabbit apolipoprotein B monoclonal antibodies in a competitive ELISA to probe the availability of apoB in rough endoplasmic reticulum, smooth endoplasmic reticulum, cis-enriched Golgi, and trans-enriched Golgi fractions from rabbit liver. The ability of each subcellular fraction to inhibit binding of monoclonal antibody to immobilized low density lipoprotein (LDL)-apoB was determined and compared with the expected inhibition based on the apoB content of the fraction. The vesicles remained closed during ELISA, demonstrated by monitoring loss of radiolabeled secretory proteins from the lumen and by measuring leakage of albumin from the vesicles. In control experiments, vesicles were permeabilized using 0.4% taurocholate. All epitopes of apoB were fully expressed in closed trans-Golgi vesicles, indicating that the membrane-bound apoB is at the cytosolic side of this fraction. In the smooth endoplasmic reticulum the epitopes were expressed between 55 and 70%, suggesting that the two pools of apoB may exist in these membranes. These results suggest that newly synthesized apoB has two possible fates. It may be incorporated into the cytosolic side of the endoplasmic reticulum from where it moves to the cytosolic side of the Golgi membrane, or newly synthesized apoB may be translocated to the lumenal surface of the endoplasmic reticulum membrane followed by assembly with lipids for secretion.
Animals↗
Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.
Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.
Animals↗