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J M Oliver

Publications and source records attributed to J M Oliver.

At least 19 recordsLinked to original sources
PubMed2006

Revealing the topography of cellular membrane domains by combined atomic force microscopy/fluorescence imaging.

Simultaneous atomic force microscopy (AFM) and confocal fluorescence imaging were used to observe in aqueous buffer the three-dimensional landscape of the inner surface of membrane sheets stripped from fixed tumor mast cells. The AFM images reveal prominent, irregularly shaped raised domains that label with fluorescent markers for both resting and activated immunoglobin E receptors (FcepsilonRI), as well as with cholera toxin-aggregated GM1 and clathrin. The latter suggests that coated pits bud from these regions. These features are interspersed with flatter regions of membrane and are frequently surrounded and interconnected by cytoskeletal assemblies. The raised domains shrink in height by approximately 50% when cholesterol is extracted with methyl-beta-cyclodextrin. Based on composition, the raised domains seen by AFM correspond to the cholesterol-enriched dark patches observed in transmission electron microscopy (TEM). These patches were previously identified as sites of signaling and endocytosis based on their localization of activated FcepsilonRI, at least 10 associated signaling molecules, and the presence of clathrin-coated pits. Overall the data suggest that signaling and endocytosis occur in mast cells from raised membrane regions that depend on cholesterol for their integrity and may be organized in specific relationship with the cortical cytoskeleton.

Animals↗
PubMed2006

Role of computed tomography and magnetic resonance imaging in aortobronchial fistula diagnosis following aortic coarctation reparative surgery. Report of two cases.

Aortobronchial fistula (ABF) is an uncommon complication of aortic coarctation repair which may occur years after successful coarctation correction. It is invariably fatal if not diagnosed and treated. ABF diagnosis poses a challenge for clinicians and radiologists because of the difficulty in detecting the fistula and the risks associated with some of the diagnostic procedures. Two cases of ABF occurring 1 and 20 years after reparative surgery of aortic coarctation are reported. The advantages and disadvantages of different imaging procedures for the evaluation of patients with suspected ABF are reviewed and the role of computed tomography angiography and magnetic resonance imaging is underlined.

Adolescent↗
PubMed2005

Thin-film theories for two-phase reactive flow models of active cell motion.

The aim of this paper is to develop a broadly-applicable and self-consistent thin-film biphasic modelling framework for the full crawling cycle of a single animal cell. A hierarchy of thin-film two-phase 'reactive flow' models is derived; between them these cover a wide range of biologically relevant parameter regimes. The mathematical properties and biological implications of the resulting systems of high-order nonlinear degenerate parabolic-elliptic evolution equations are investigated. Linear-stability arguments suggest the formation of highly localized regions of high or low network density associated with small irregular oscillations or 'ruffling' of the plasma membrane. Local analyses at the contact line identify the classes of admissible contact-line conditions, through which we study for the first time the effect on the cell-scale motion of the 'mesoscopic' contact-line physics, which consists of the chemical and mechanical mechanisms for protrusive and retractive force generation near the outer cell periphery. One of the formulations is used to develop a minimal model for cell body translocation over a thin pseudopod, which predicts that myosin-driven contraction is not essential for rapid translocation. An analytic prediction for the translocation speed is given in terms of the network viscosity and slip coefficient (a parameter measuring the adhesion strength), of the membrane tension and of the thicknesses of the pseudopod and actin cortex; this is in good agreement with the translocation speed of osteoblasts on biomaterial substrates commonly used for orthopaedic implants. Limitations of the modelling approach and directions for future work are outlined.

Actins↗
PubMed2002

Sinus venosus syndrome: atrial septal defect or anomalous venous connection? A multiplane transoesophageal approach.

OBJECTIVE: To discuss the anatomical features of sinus venosus atrial defect on the basis of a comprehensive transoesophageal echocardiography (TOE) examination and its relation to surgical data. METHODS: 24 patients (13 men, 11 women, mean (SD) age 37 (17) years, range 17-73 years) with a posterior interatrial communication closely related to the entrance of the superior (SVC) or inferior vena cava (IVC) who underwent TOE before surgical repair. Records of these patients were retrospectively reviewed and compared with surgical assessments. RESULTS: In 13 patients, TOE showed a deficiency in the extraseptal wall that normally separates the left atrium and right upper pulmonary vein from the SVC and right atrium. This deficiency unroofed the right upper pulmonary vein, compelling it to drain into the SVC, which overrode the intact atrial septum. In three patients, TOE examination showed a defect in the wall of the IVC, which continued directly into the posterior border of the left atrium. Thus, the intact muscular border of the atrial septum was overridden by the mouth of the IVC, which presented a biatrial connection. In the remaining eight patients, the defect was located in the muscular posterior border of the fossa ovalis. A residuum of atrial septum was visualised in the superior margin of the defect. Neither caval vein overriding nor anomalous pulmonary vein drainage was present. CONCLUSIONS: Sinus venosus syndrome should be regarded as an anomalous venous connection with an interatrial communication outside the confines of the atrial septum, in the unfolding wall that normally separates the left atrium from either caval vein. It results in overriding of the caval veins across the intact atrial septum and partial pulmonary vein anomalous drainage. It should be differentiated from posterior atrial septal defect without overriding or anomalous venous connections.

Adolescent↗
PubMed2001

Real time analysis of the affinity regulation of alpha 4-integrin. The physiologically activated receptor is intermediate in affinity between resting and Mn(2+) or antibody activation.

This work examines the affinity of alpha(4)beta(1)-integrin and whether affinity regulation by G protein-coupled receptor (GPCR) and chemokines receptors is compatible with cell adhesion mediated between alpha(4)-integrin and vascular cell adhesion molecule-1. We used flow cytometry to examine the binding of a fluorescent derivative of an LDV peptide (Chen, L. L., Whitty, A., Lobb, R. R., Adams, S. P., and Pepinsky, R. B. (1999) J. Biol. Chem. 274, 13167-13175) to several cell lines and leukocytes with alpha(4)-integrin ranging from about 2,000 to 100,000 sites/cell. The results support the idea that alpha(4)-integrins exhibit multiple affinities and that affinity changes are regulated by the dissociation rate and conformation. The affinity varies by 3 orders of magnitude with the affinity induced by binding mAb TS2/16 plus Mn(2+) > Mn(2+) ' TS2/16 > activation because of occupancy of GPCR or chemokines receptor > resting receptors. A significant fraction of the receptors respond to the activating process. The change in alpha(4)-integrin affinity and the corresponding change in off rates mediated by GPCR receptor activation are rapid and transient, and their duration depends on GPCR desensitization. The affinity changes mediated by IgE receptor or interleukin-5 receptor persist longer. It appears that the physiologically active state of the alpha(4)-integrin, determined by inside-out signaling, has similar affinity in several cell types.

Antibodies, Monoclonal↗
PubMed2001

Overcoming the signaling defect of Lyn-sequestering, signal-curtailing FcepsilonRI dimers: aggregated dimers can dissociate from Lyn and form signaling complexes with Syk.

Clustering the tetrameric (alphabetagamma(2)) IgE receptor, FcepsilonRI, on basophils and mast cells activates the Src-family tyrosine kinase, Lyn, which phosphorylates FcepsilonRI beta and gamma subunit tyrosines, creating binding sites for the recruitment and activation of Syk. We reported previously that FcepsilonRI dimers formed by a particular anti-FcepsilonRI alpha mAb (H10) initiate signaling through Lyn activation and FcepsilonRI subunit phosphorylation, but cause only modest activation of Syk and little Ca(2+) mobilization and secretion. Curtailed signaling was linked to the formation of unusual, detergent-resistant complexes between Lyn and phosphorylated receptor subunits. Here, we show that H10-FcepsilonRI multimers, induced by adding F(ab')(2) of goat anti-mouse IgG to H10-treated cells, support strong Ca(2+) mobilization and secretion. Accompanying the recovery of signaling, H10-FcepsilonRI multimers do not form stable complexes with Lyn and do support the phosphorylation of Syk and phospholipase Cgamma2. Immunogold electron microscopy showed that H10-FcepsilonRI dimers colocalize preferentially with Lyn and are rarely within the osmiophilic "signaling domains" that accumulate FcepsilonRI and Syk in Ag-treated cells. In contrast, H10-FcepsilonRI multimers frequently colocalize with Syk within osmiophilic patches. In sucrose gradient centrifugation analyses of detergent-extracted cells, H10-treated cells show a more complete redistribution of FcepsilonRI beta from heavy (detergent-soluble) to light (Lyn-enriched, detergent-resistant) fractions than cells activated with FcepsilonRI multimers. We hypothesize that restraints imposed by the particular orientation of H10-FcepsilonRI dimers traps them in signal-initiating Lyn microdomains, and that converting the dimers to multimers permits receptors to dissociate from Lyn and redistribute to separate membrane domains that support Syk-dependent signal propagation.

Animals↗
PubMed2001

Immunohistochemical detection of human basophils in postmortem cases of fatal asthma.

The role of human basophils in bronchial asthma has been hard to define. In this study, we used the basophil-specific monoclonal antibody (mAb), 2D7, in postmortem lung sections from individuals who die in status asthmaticus (fatal asthma [FA]) to determine if the pathology of FA is associated with an increase in basophil numbers in the lung. As controls, we used lung sections of patients who had a history of asthma but died from nonasthmatic causes (nonfatal asthma [NFA]) as well as patients with no history of asthma (control [C]). In lung sections from all three groups, basophils were scattered throughout the large and small airways, airway epithelium, submucosa, and alveolar walls. The numbers of basophils in the lungs of patients with FA ranged from 41 to 119 cells/mm(2), significantly more than the numbers of basophils in lungs from individuals with a history of asthma (NFA; 0 to 16 cells/ mm(2)) and in the control lungs (C; 0 to 13 cells/mm(2)). In contrast, CD45-positive cells were not significantly different in the airways of FA and NFA, although there were significant increases in the two groups compared with control subjects. In summary, basophil infiltration was significantly increased in lungs from individuals who died from asthma, supporting the hypothesis that basophils are involved in the pathogenesis of FA.

Adolescent↗
PubMed2001

High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc(epsilon)RI and LAT.

In mast cells, cross-linking the high-affinity IgE receptor (Fc(epsilon)RI) initiates the Lyn-mediated phosphorylation of receptor ITAMs, forming phospho-ITAM binding sites for Syk. Previous immunogold labeling of membrane sheets showed that resting Fc(epsilon)RI colocalize loosely with Lyn, whereas cross-linked Fc(epsilon)RI redistribute into specialized domains (osmiophilic patches) that exclude Lyn, accumulate Syk, and are often bordered by coated pits. Here, the distribution of Fc(epsilon)RI beta is mapped relative to linker for activation of T cells (LAT), Grb2-binding protein 2 (Gab2), two PLCgamma isoforms, and the p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase), all implicated in the remodeling of membrane inositol phospholipids. Before activation, PLCgamma1 and Gab2 are not strongly membrane associated, LAT occurs in small membrane clusters separate from receptor, and PLCgamma2, that coprecipitates with LAT, occurs in clusters and along cytoskeletal cables. After activation, PLCgamma2, Gab2, and a portion of p85 colocalize with Fc(epsilon)RI beta in osmiophilic patches. LAT clusters enlarge within 30 s of receptor activation, forming elongated complexes that can intersect osmiophilic patches without mixing. PLCgamma1 and another portion of p85 associate preferentially with activated LAT. Supporting multiple distributions of PI3-kinase, Fc(epsilon)RI cross-linking increases PI3-kinase activity in anti-LAT, anti-Fc(epsilon)RIbeta, and anti-Gab2 immune complexes. We propose that activated mast cells propagate signals from primary domains organized around Fc(epsilon)RIbeta and from secondary domains, including one organized around LAT.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Discrete subaortic stenosis in adults: increased prevalence and slow rate of progression of the obstruction and aortic regurgitation.

OBJECTIVES: We sought to determine the prevalence and rate of progression of left ventricular outflow tract obstruction (LVOTO) and aortic regurgitation (AR) in adults with discrete subaortic stenosis (DSS). BACKGROUND: Discrete subaortic stenosis is an uncommon form of LVOTO, with rapid hemodynamic progression in children, but the prevalence and rate of progression in adults have not been studied so far. METHODS: The prevalence of DSS was determined in 2,057 consecutive adults diagnosed with congenital heart disease (CHD). The relationship between LVOTO on Doppler echocardiography and patient age was analyzed. Sequential changes in LVOTO and AR were determined for patients with two or more Doppler echocardiograms obtained with at least a two-year interval. RESULTS: A total of 134 adults (mean age 31 +/- 17 years) were diagnosed with DSS. The prevalence was 6.5% for all adults with CHD. Sixty patients (44%) had other associated CHD. The mean age of 29 patients who had undergone an operation for DSS during their adult life (56 +/- 15 years) was significantly higher than that of 64 patients (27 +/- 13 years) who had not required a surgical intervention (p < 0.0001). A significant relationship between LVOTO and patient age (r = 0.61, p < 0.0001) was found: 21 +/- 16 mm Hg in patients <25 years old, 51 +/- 47 mm Hg for those between 25 and 50 years old, and 78 +/- 36 mm Hg for those >50 years old. The LVOTO increased from 39.2 +/- 28 to 46.8 +/- 34 mm Hg (p = 0.01) during a mean follow-up of 4.8 +/- 1.8 years in 25 patients. The slope of the change in LVOTO was 2.25 +/- 4.7 mm Hg per year of follow-up. Aortic regurgitation was detected by color Doppler imaging in 109 patients (81%), but it was hemodynamically significant in <20%. An increase in the mean degree of AR over time was not significant (baseline: 1.3 +/- 0.8; follow-up: 1.5 +/- 0.9; p = 0.096). CONCLUSIONS: The prevalence of DSS is increasing in adults due to the greater number of repaired CHDs that develop into evolutive DSS. In contrast to infants and children, adults with DSS show a slow rate of LVOTO progression. Aortic regurgitation is a common but usually mild and nonprogressive consequence. The current indications for surgical intervention should be revised.

Adult↗
PubMed2001

Left atrial dissection: pathogenesis, clinical course, and transesophageal echocardiographic recognition.

Left atrial dissection is an uncommon entity. It is generally associated with mitral valve replacement, but other predisposing factors should be considered in pathogenesis. We discuss a series of 11 patients with pathologically confirmed left atrial dissection who had been diagnosed previously by transesophageal echocardiography. Predisposing factors and surgical or pathologic findings were reviewed to identify the pathogenic mechanism and to explain the clinical course, hemodynamic disorder, and echocardiographic features. Dissection of the coronary sinus secondary to retrograde cardioplegia, endocarditis, cardiac rupture after myocardial infarction, and blunt chest trauma also could be related to its development. Transesophageal echocardiography identified a mobile intimal flap of the atrial wall that was creating a false chamber and allowed accurate diagnosis of prosthetic mitral valve function, endocarditis complications, and a left ventricular pseudoaneurysm after acute myocardial infarction. Color flow Doppler was particularly useful in identifying complications: communication between the false chamber and true left atria, permitting mitral regurgitation through the periannular route; development of atrial shunts; and severe tricuspid regurgitation caused by disruption of the anterior papillary muscle.

Adult↗
PubMed2001

[Transesophageal echocardiographic diagnosis of a ruptured sinus of valsalva aneurysm with right atrium fistula].

Congenital aneurysms of the sinus of Valsalva are relatively rare, tending to be most frequent in adults. Untreated, there is a substantial risk of complication due to bacterial endocarditis and, if rupture occurs, rapid and progressive cardiac insufficiency is fatal at short term. We report the case of a 53-year-old male with a ruptured right sinus of Valsalva aneurysm, resulting in an anomalous right atrium fistula. Symptoms presented, clinical diagnosis and, above all, transesophageal echocardiography were crucial in the final diagnosis leading to an early and satisfactory surgical intervention. Catheterization and angiography were not definitive. Echocardiographic data are described and a bibliography of relevant research articles is provided.

Aortic Aneurysm↗
PubMed2001

Regulation of the very late antigen-4-mediated adhesive activity of normal and nonreleaser basophils: roles for Src, Syk, and phosphatidylinositol 3-kinase.

Normal human basophils express the integrin, VLA-4, and cross-linking their high-affinity IgE receptor, FcepsilonRI, increases their VLA-4-dependent adhesion to VCAM-1-transfected Chinese hamster ovary (CHO) cells. Here we show that the FcepsilonRI-mediated up-regulation of normal basophil VLA-4 adhesion is abolished by the Src inhibitor, PP1, the Syk inhibitor, ER-27319, and the phosphatidylinositol 3-kinase inhibitor, wortmannin. PP1, but not ER-27319 or wortmannin, also reduces basal adhesion and adhesion stimulated by chemotactic peptide, by Ca(++) ionophores, and by phorbol myristate acetate (PMA). Nonreleaser basophils (the consistently Syk-deficient, variably Lyn-deficient, severely degranulation-impaired cells found in about 10% of donors) share the PP1 phenotype of lowered basal adhesion, no FcepsilonRI-mediated adhesion up-regulation, and reduced adhesive responses to chemoattractant ionophores and PMA. These results implicate Src kinases in the control of basal VLA-4 activity and place Syk and phosphatidylinositol 3-kinase in the pathway linking FcepsilonRI cross-linking to VLA-4 up-regulation. Both Src and Syk-regulated components of adhesion may be impaired in nonreleaser basophils.

Acridines↗
PubMed2000

Multiple defects in Fc epsilon RI signaling in Syk-deficient nonreleaser basophils and IL-3-induced recovery of Syk expression and secretion.

Human basophils respond to Ag-induced cross-linking of their high affinity IgE receptor, FcepsilonRI, by releasing histamine and other mediators from granules, producing IL-4 and other cytokines and, as shown in this study, by forming membrane ruffles and showing increased very late Ag-4 (VLA-4)-mediated adhesion to VCAM-1-expressing target cells. We have identified five blood donors whose basophils lack detectable levels of the FcepsilonRI-associated protein tyrosine kinase, Syk. Despite showing no obvious ultrastructural differences from normal basophils, nonreleaser basophils fail to form membrane ruffles, to show increased VLA-4-mediated adhesive activity, or to produce IL-4 in response to FcepsilonRI cross-linking. Although Syk protein levels are suppressed in basophils from all five donors, Syk mRNA is consistently present. Furthermore, culturing nonreleaser basophils for 4 days with IL-3 restores Syk protein expression and FcepsilonRI-mediated histamine release. Understanding the reversible suppression of Syk protein expression in nonreleaser basophils, and learning to replicate this property in patients with allergic inflammation could be a powerful and specific way to limit symptomatic disease.

Antibodies, Anti-Idiotypic↗
PubMed2000

Immunologically mediated signaling in basophils and mast cells: finding therapeutic targets for allergic diseases in the human FcvarepsilonR1 signaling pathway.

The high affinity IgE receptor, FcvarepsilonRI, plays key roles in an array of acute and chronic human allergic reactions including asthma, allergic rhinitis, atopic dermatitis, urticaria and anaphylaxis. In humans and rodents, this receptor is found at high levels on basophils and mast cells where its activation by IgE and multivalent antigen produces mediators and cytokines responsible for FcvarepsilonRI-dependent acute inflammation. Mast cells can additionally contribute to sustained inflammatory responses by internalizing antigen bound to IgE-FcvarepsilonRI complexes for processing to peptides and presentation to T cells. In humans, the FcvarepsilonRI is also expressed, at lower density, on monocytes, macrophages and dendritic cells (DC) where its likely functions again include both signaling to mediator and cytokine production and antigen presentation. Our laboratories have focused on defining the earliest steps in the FcvarepsilonRI signaling cascade in basophils and mast cells and on developing new routes to control allergic inflammation based on inhibiting these events. Here, we describe novel strategies to limit antigen-stimulated FcvarepsilonRI signaling by: (1) sequestering the FcvarepsilonRI-associated protein-tyrosine kinase, Lyn, that initiates FcvarepsilonRI signaling; (2) eliminating; or (3) inactivating the protein-tyrosine kinase, Syk, that propagates FcvarepsilonRI signaling; and (4) establishing inhibitory crosstalk between FcvarepsilonRI and a co-expressed receptor, FcgammaRII, that again limits FcvarepsilonRI-mediated Syk activation. These strategies may form the basis for new therapies for allergic inflammation.

Animals↗
PubMed2000

Observing FcepsilonRI signaling from the inside of the mast cell membrane.

We have determined the membrane topography of the high-affinity IgE receptor, FcstraightepsilonRI, and its associated tyrosine kinases, Lyn and Syk, by immunogold labeling and transmission electron microscopic (TEM) analysis of membrane sheets prepared from RBL-2H3 mast cells. The method of Sanan and Anderson (Sanan, D.A., and R.G.W. Anderson. 1991. J. Histochem. Cytochem. 39:1017-1024) was modified to generate membrane sheets from the dorsal surface of RBL-2H3 cells. Signaling molecules were localized on the cytoplasmic face of these native membranes by immunogold labeling and high-resolution TEM analysis. In unstimulated cells, the majority of gold particles marking both FcepsilonRI and Lyn are distributed as small clusters (2-9 gold particles) that do not associate with clathrin-coated membrane. Approximately 25% of FcepsilonRI clusters contain Lyn. In contrast, there is essentially no FcepsilonRI-Syk colocalization in resting cells. 2 min after FcepsilonRI cross-linking, approximately 10% of Lyn colocalizes with small and medium-sized FcepsilonRI clusters (up to 20 gold particles), whereas approximately 16% of Lyn is found in distinctive strings and clusters at the periphery of large receptor clusters (20-100 gold particles) that form on characteristically osmiophilic membrane patches. While Lyn is excluded, Syk is dramatically recruited into these larger aggregates. The clathrin-coated pits that internalize cross-linked receptors bud from membrane adjacent to the Syk-containing receptor complexes. The sequential association of FcstraightepsilonRI with Lyn, Syk, and coated pits in topographically distinct membrane domains implicates membrane segregation in the regulation of FcstraightepsilonRI signaling.

Animals↗
PubMed2000

[Aortic pseudocoarctation complicated by a giant pseudoaneurysm].

Pseudocoarctation of the aorta is an infrequent anomaly caused by the elongation and the congenital kinking of the aorta. We present a case of pseudocoarctation of the aorta with saccular aneurysm complicated with a large pseudoaneurysm. Both, magnetic resonance and aortography showed an aneurysm of the aortic isthmus that extended/progressed as pseudoaneurysm towards the neck. The patient was asymptomatic but due to the high risk of rupture, she underwent surgical reparation. The revision of the literature and our experience with this case show that pseudocoarctation of the aorta is not always a benign pathology and that surgical reparation should be performed in all those cases that are complicated by aneurysm.

Adult↗
PubMed2000

[Stent dilatation of pulmonary artery stenosis in the adult patient with congenital heart disease].

Stents have been previously used to resolve stenoses of branch pulmonary arteries in children. We report 3 patients, with mean age of 22.7 +/- 4.7 years and pulmonary artery stenosis after palliative surgery in whom we implanted seven stents in four procedures. Six P308 Palmaz, overlapped two by two, were implanted by venous femoral approach in two patients, receiving four in the first case and the other two in the third case. In the second case, a NIR type stent was implanted through femoral artery in the right pulmonary artery. Stenosis diameter enlarged from 5.3 +/- 2.3 to 14.4 +/- 4.2 mm and the pressure gradient through stenosis fell from 40.6 +/- 15.3 to 6. 5 +/- 5 mmHg. All stents are well deployed and there are two patients waiting for total correction (previously not feasible) during a follow-up of 30.6 +/- 6.1 months.

Adult↗