tbuckley/cabot-search huggingface dataset:
Distinct molecular forms of human T cell receptor gamma/delta detected on viable T cells by a monoclonal antibody.
Authors: J Borst, J J van Dongen, R L Bolhuis, P J Peters, D A Hafler, E de Vries, R J van de Griend
Journal: The Journal of Experimental Medicine (1988)

A second type of TCR molecule has been identified on human and murine T lymphocytes, which involves the protein products of the gamma and delta genes. T lymphocytes bearing this receptor may constitute a separate cell lineage with a distinct immune function. We have produced an mAb, which specifically detects human TCR-gamma/delta in native as well as denatured states, this in contrast to previously used anti-gamma chain peptide sera, which only reacted with denatured protein. The receptor occurs in different molecular forms, with or without interchain disulphide bonds, in which a delta chain may or may not be detected by cell surface iodination. The mAb is reactive with all these receptor forms. Therefore, this antibody could be used to determine the expression of TCR-gamma/delta on viable human T lymphocytes. In normal individuals, TCR-gamma/delta was found on a subset composing 2-7% of CD3+ lymphocytes in peripheral blood and 0.1-1.0% in thymus. The majority of these cells do not express the CD4 or CD8 antigens, although a significant percentage of CD8+ cells was found. TCR-gamma/delta+ cells in peripheral blood are resting lymphocytes, as judged by ultrastructural analysis. T cell clones with different receptor types can display MHC-nonrestricted cytolytic activity, which is shown to be induced by the culture conditions, most likely by growth factors such as IL-2. This strongly suggests that TCR-gamma/delta does not play a role in target cell recognition in MHC-nonrestricted cytotoxicity. The anti-TCR-gamma/delta antibody can specifically induce cytotoxic activity in clones expressing the receptor, but in addition inhibit growth factor induced cytotoxicity, which indicates a regulatory role of the TCR-gamma/delta/CD3 complex in MHC-nonrestricted cytotoxicity.
Distinct cell-specific control of autoimmunity and infection by FcγRIIb
Authors: Rebecca J. Brownlie, Kate E. Lawlor, Heather A. Niederer, Antony J. Cutler, Zou Xiang, Menna R. Clatworthy, R. Andres Floto, David R. Greaves, Paul A. Lyons, Kenneth G.C. Smith
Journal: The Journal of Experimental Medicine (2008)

FcγRIIb is an inhibitory Fc receptor expressed on B cells and myeloid cells. It is important in controlling responses to infection, and reduced expression or function predisposes to autoimmunity. To determine if increased expression of FcγRIIb can modulate these processes, we created transgenic mice overexpressing FcγRIIb on B cells or macrophages. Overexpression of FcγRIIb on B cells reduced the immunoglobulin G component of T-dependent immune responses, led to early resolution of collagen-induced arthritis (CIA), and reduced spontaneous systemic lupus erythematosus (SLE). In contrast, overexpression on macrophages had no effect on immune responses, CIA, or SLE but increased mortality after Streptococcus pneumoniae infection. These results help define the role of FcγRIIb in immune responses, demonstrate the contrasting roles played by FcγRIIb on B cells and macrophages in the control of infection and autoimmunity, and emphasize the therapeutic potential for modulation of FcγRIIb expression on B cells in inflammatory and autoimmune disease.
The peptide-binding motif for the human transporter associated with antigen processing.
Authors: P M van Endert, D Riganelli, G Greco, K Fleischhauer, J Sidney, A Sette, J F Bach
Journal: The Journal of Experimental Medicine (1995)

Presentation of antigenic peptides by human leukocyte antigen class I molecules is dependent on peptide transport into the endoplasmic reticulum by the transporters associated with antigen processing (TAP) (Germain, R. N. 1994. Cell. 76:287-299). This translocation step is currently regarded as permissive for all peptides with COOH-terminal residues capable of binding to HLA class I molecules (Momburg, F., J. Roelse, J. C. Howard, G. W. Butcher, G.J. Hämmerling, and J.J. Neefjes. 1994. Nature (Lond.). 367:648-651). In this report, we show that the human transporter selects peptides according to a binding motif based on the strong effects on peptide affinity of the three NH2-terminal positions and the COOH-terminal residues. TAP favors strongly hydrophobic residues in position 3 (P3) and hydrophobic or charged residues in P2, whereas aromatic or acidic residues in P1, as well as Pro in P1 and P2, have strong deleterious effects. Selection of naturally presented peptides by the transporter is suggested by their higher average affinity for TAP, as compared to nonselected peptides. The TAP preferences in the three NH2-terminal positions correspond to those of the vast majority of human leukocyte antigen class I alleles, but they represent an obstacle for peptide supply to some alleles, e.g., the B7-like group. We propose that peptides binding to these alleles, and in general, peptides with TAP affinities below a certain threshold, may be transported as extended precursors.
Registry of Transcatheter Aortic-Valve Implantation in High-Risk Patients
Authors: Martine Gilard, Hélène Eltchaninoff, Bernard Iung, Patrick Donzeau-Gouge, Karine Chevreul, Jean Fajadet, Pascal Leprince, Alain Leguerrier, Michel Lievre, Alain Prat, Emmanuel Teiger, Thierry Lefevre, Dominique Himbert, Didier Tchetche, Didier Carrié, Bernard Albat, Alain Cribier, Gilles Rioufol, Arnaud Sudre, Didier Blanchard, Frederic Collet, Pierre Dos Santos, Nicolas Meneveau, Ashok Tirouvanziam, Christophe Caussin, Philippe Guyon, Jacques Boschat, Herve Le Breton, Frederic Collart, Remi Houel, Stephane Delpine, Geraud Souteyrand, Xavier Favereau, Patrick Ohlmann, Vincent Doisy, Gilles Grollier, Antoine Gommeaux, Jean-Philippe Claudel, Francois Bourlon, Bernard Bertrand, Eric Van Belle, Marc Laskar
Journal: New England Journal of Medicine (2012)

Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2.
Mechanism of Syncope in Patients With Bundle Branch Block and Negative Electrophysiological Test
Authors: Michele Brignole, Carlo Menozzi, Angel Moya, Roberto Garcia-Civera, Luis Mont, Miguel Alvarez, Francisco Errazquin, Julio Beiras, Nicola Bottoni, Paolo Donateo
Journal: Circulation (2001)

Background In patients with syncope and bundle branch block (BBB), syncope is suspected to be attributable to a paroxysmal atrioventricular (AV) block, but little is known of its mechanism when electrophysiological study is negative. Methods and Results We applied an implantable loop recorder in 52 patients with BBB and negative conventional workup. During a follow-up of 3 to 15 months, syncope recurred in 22 patients (42%), the event being documented in 19 patients after a median of 48 days. The most frequent finding, recorded in 17 patients, was one or more prolonged asystolic pause mainly attributable to AV block; the remaining 2 patients had normal sinus rhythm or sinus tachycardia. The onset of the bradycardic episodes was always sudden but was sometimes preceded by ventricular premature beats. The median duration of the arrhythmic event was 47 seconds. An additional 3 patients developed nonsyncopal persistent III-degree AV block, and 2 patients had presyncope attributable to AV block with asystole. No patients suffered injury attributable to syncopal relapse. Conclusions In patients with BBB and negative electrophysiological study, most syncopal recurrences have a homogeneous mechanism that is characterized by prolonged asystolic pauses, mainly attributable to sudden-onset paroxysmal AV block.
Atherosclerosis Reviews, volume 24: High Density Lipoproteins - Patho-physiology and Clinical Relevance.
Authors: M. Aviram
Journal: Cardiovascular Research (1994)

Journal Article Atherosclerosis Reviews, volume 24: High Density Lipoproteins - Patho-physiology and Clinical Relevance. Get access Michael Aviram Michael Aviram Haifa, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 11, November 1994, Page 1735, https://doi.org/10.1093/cvr/28.11.1735b Published: 01 November 1994
High Shed Antigen Levels within Tumors: An Additional Barrier to Immunoconjugate Therapy
Authors: Yujian Zhang, Ira Pastan
Journal: Clinical Cancer Research (2008)

Abstract Shedding of cell surface antigens is an important biological process that is used by cells to modulate responses to signals in the extracellular environment. Because antibody-based therapies of cancer target cell surface antigens, it is important to understand more about the shedding process and how it affects tumor responses to this type of therapy. Up to now most attention has been focused on measuring the concentration of shed antigens in the blood and using these to determine the presence of a tumor and as a measure of response. The recent finding that the concentration of the tumor antigen mesothelin is extremely high within the interstitial space of tumors, where it can block antibody action, and that the concentration of shed mesothelin within the tumor is lowered by chemotherapy has important implications for the successful treatment of solid tumors by immunoconjugates and whole antibodies.
Outcome of Treatment in Adults With Acute Lymphoblastic Leukemia: Analysis of the LALA-94 Trial
Authors: Xavier Thomas, Jean-Michel Boiron, Françoise Huguet, Hervé Dombret, Ken Bradstock, Norbert Vey, Tibor Kovacsovics, André Delannoy, Nathalie Fegueux, Pierre Fenaux, Aspasia Stamatoullas, Jean-Paul Vernant, Olivier Tournilhac, Agnès Buzyn, Oumedaly Reman, Christiane Charrin, Claude Boucheix, Jean Gabert, Véronique Lhéritier, Denis Fiere
Journal: Journal of Clinical Oncology (2004)

We analyzed the benefits of a risk-adapted postremission strategy in adult lymphoblastic leukemia (ALL), and re-evaluated stem-cell transplantation (SCT) for high-risk ALL.A total of 922 adult patients entered onto the trial according to risk groups: standard-risk ALL (group 1), high-risk ALL (group 2), Philadelphia chromosome-positive ALL (group 3), and CNS-positive ALL (group 4). All received a standard four-drug/4-week induction course. Patients from group 1 who achieved a complete remission (CR) after one course of induction therapy were randomly assigned between intensive and less intensive postremission chemotherapy, whereas those who achieved CR after salvage therapy were then included in group 2. Patients in groups 2, 3, and 4 with an HLA-identical sibling were assigned to allogeneic SCT. In groups 3 and 4, autologous SCT was offered to all other patients, whereas in group 2 they were randomly assigned between chemotherapy and autologous SCT.Overall, 771 patients achieved CR (84%). Median disease-free survival (DFS) was 17.5 months, with 3-year DFS at 37%. In group 1, the 3-year DFS rate was 41%, with no difference between arms of postremission randomization. In groups 2 and 4, the 3-year DFS rates were 38% and 44%, respectively. In group 2, autologous SCT and chemotherapy resulted in comparable median DFS. Patients with an HLA-matched sibling (groups 2 and 4) had improved DFS. Three-year DFS was 24% in group 3.Allogeneic SCT improved DFS in high-risk ALL in the first CR. Autologous SCT did not confer a significant benefit over chemotherapy for high-risk ALL.
Beta-2 microglobulin is an amyloidogenic protein in man.
Authors: P D Gorevic, T T Casey, W J Stone, C R DiRaimondo, F C Prelli, B Frangione
Journal: Journal of Clinical Investigation (1985)

Curvilinear fibrils with the tinctorial properties of amyloid were isolated from a patient with bone and joint involvement complicating chronic dialysis for renal disease. Subunit fractions of 24,000 and 12,000 mol wt were identified after gel filtration under dissociating conditions, the latter containing a significant amount of a dimer of the former. This was confirmed by Edman degradation of each fraction, which yielded the amino terminal sequence of normal human beta-2 microglobulin (B2M) to residues 20 and 30, respectively. The size of the subunit protein (12,000 mol wt) and the amino acid composition make it likely that intact B2M is a major constituent of the fibrils. B2M is thus another example of a low molecular weight serum protein, with a prominent beta-pleated sheet structure, that may adopt the fibrillar configuration of amyloid in certain pathologic states.
Power in Numbers: Meta-analysis to Identify Inhibitor-Sensitive Tumor Genotypes
Authors: Geoffrey R. Oxnard, Pasi A. Jänne
Journal: Clinical Cancer Research (2013)

Widespread tumor genotyping has increased the complexity of lung cancer care, often identifying mutations of uncertain clinical significance. In the accompanying article, the authors carried out a meta-analysis of the published literature on EGF receptor (EGFR) genotype and erlotinib/gefitinib sensitivity to develop a publicly accessible database to inform patient care.
Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island
Authors: Joy C. Lin, Shinwu Jeong, Gangning Liang, Daiya Takai, Merhnaz Fatemi, Yvonne C. Tsai, Gerda Egger, Einav Nili Gal-Yam, Peter A. Jones
Journal: Cancer Cell (2007)
Complement Interaction with Trypanosomatid Promastigotes in Normal Human Serum
Authors: Mercedes Domínguez, Inmaculada Moreno, Margarita López-Trascasa, Alfredo Toraño
Journal: The Journal of Experimental Medicine (2002)

In normal human serum (NHS), axenic promastigotes of Crithidia, Phytomonas, and Leishmania trigger complement activation, and from 1.2 to 1.8 × 105 C3 molecules are deposited per promastigote within 2.5 min. In Leishmania, promastigote C3 binding capacity remains constant during in vitro metacyclogenesis. C3 deposition on promastigotes activated through the classical complement pathway reaches a 50% maximum after ∼50 s, and represents &amp;gt;85% of total C3 bound. In C1q- and C2-deficient human sera, promastigotes cannot activate the classical pathway (CP) unless purified C1q or C2 factors, respectively, are supplemented, demonstrating a requirement for CP factor in promastigote C3 opsonization. NHS depleted of natural anti-Leishmania antibodies cannot trigger promastigote CP activation, but IgM addition restores C3 binding. Furthermore, Leishmania binds natural antibodies in ethylenediaminetetracetic acid (EDTA)-treated NHS; after EDTA removal, promastigote-bound IgM triggers C3 deposition in natural antibody-depleted NHS. Serum collectins and pentraxins thus do not participate significantly in NHS promastigote C3 opsonization. Real-time kinetic analysis of promastigote CP-mediated lysis indicates that between 85–95% of parasites are killed within 2.5 min of serum contact. These data indicate that successful Leishmania infection in man must immediately follow promastigote transmission, and that Leishmania evasion strategies are shaped by the selective pressure exerted by complement.
Neural “Ignition”: Enhanced Activation Linked to Perceptual Awareness in Human Ventral Stream Visual Cortex
Authors: Lior Fisch, Eran Privman, Michal Ramot, Michal Harel, Yuval Nir, Svetlana Kipervasser, Fani Andelman, Miri Y. Neufeld, Uri Kramer, Itzhak Fried, Rafael Malach
Journal: Neuron (2009)
Detection of acute myocardial infarction in closed-chest dogs by analysis of regional two-dimensional echocardiographic gray-level distributions.
Authors: D J Skorton, H E Melton, N G Pandian, J Nichols, S Koyanagi, M L Marcus, S M Collins, R E Kerber
Journal: Circulation Research (1983)

We hypothesized that acute myocardial infarction could be detected in standard two-dimensional echocardiograms of closed-chest dogs by evaluating regional echo amplitude distributions using computerized image analysis. We tested this hypothesis by performing standard, 2.4 MHz two-dimensional echoes before and 2 days after circumflex coronary occlusion in seven closed-chest dogs. Control and infarcted regions of interest were studied in digitized stop-frame images. Average gray level was calculated for each region of interest, and the shape of the gray-level distribution was analyzed by calculation of skewness and kurtosis and by qualitative features of shape. Average gray level increased significantly from the pre- to postocclusion images in the infarcted regions (16.7 +/- 4.2 vs. 32.4 +/- 4.4 units, P less than 0.01), but not in the control regions (17.4 +/- 4 vs. 22.3 +/- 5.5., P = NS). Average gray level could not distinguish between infarcted and normal regions within the postocclusion images (36 +/- 5.2 vs. 33.6 +/- 5.8, P = NS). Three independent observers qualitatively evaluated histogram shape and correctly identified 7/7 MI regions (100% sensitivity) and 14/20 normal regions (70% specificity). Quantitatively, infarct regions exhibited a significant decrease in kurtosis from pre- to postocclusion images (7.1 +/- 4.0 vs. 5.2 +/- 2.9, P = NS). Within postocclusion images, infarcted regions displayed a significantly lower kurtosis than did normal regions (0.27 +/- .47 vs. 2.5 +/- 1.0, P less than .01). We conclude that acute myocardial infarction may be detected in closed-chest dogs by analyzing regional echo amplitude data from standard two-dimensional echocardiograms.
The incidence and distribution of stress fractures in elite tennis players
Authors: J Maquirriain, J P Ghisi
Journal: British Journal of Sports Medicine (2006)

Background: Modern professional tennis involves powerful movements repeatedly subjecting the musculoskeletal system to heavy mechanical load. Thus tennis players are exposed to high risk of overuse injuries including stress fractures. Objective: To determine the incidence and distribution of stress fractures in elite tennis players. Study design: Retrospective cohort study. Methods: The cohort study population consisted of 139 elite players (mean (SD) age, 20.0 (5.0) years; 48 female, 91 male). Stress fractures were identified and confirmed radiologically from medical records during a two year period. Injuries were analysed according to age, sex, site, severity, delay in diagnosis, and time needed to return to sports. Results: 15 players sustained 18 stress fractures, corresponding to an overall case incidence of 12.9% (95% confidence interval (CI), 8.1 to 20.0). The tarsal navicular was most affected (n = 5; 27%), followed by the pars interarticularis (n = 3; 16%), the metatarsals (n = 3; 16%), the tibia (n = 2; 11%) and the lunate (n = 2; 11%). Magnetic resonance imaging showed a greater incidence of “high grade” lesions (94.4%). Stress fracture incidence was significantly higher in juniors (20.3% (95% CI, 11.4 to 33.2)) than in professional players (7.5% (2.8 to 15.6)) (p = 0.045). Conclusions: There was a high absolute risk (12.9%) of stress fractures in elite tennis players over a two year period. Junior players were at highest risk. The lesions are a major cause of disruption both of training and of competition. Risk factors should therefore be identified and prevention emphasised.
Prediction of Diabetic Retinopathy from Clinical Variables and Color Vision Data
Authors: Peter A Aspinall, Paul R Kinnear, Leslie J P Duncan, Basil F Clarke
Journal: Diabetes Care (1983)

Predictions about the onset of retinopathy in 295 diabetic patients, all originally having no evidence of retinopathy, have been made in a longitudinal study over 7 yr. Out of many color vision tests and clinical variables, the best individual predictor was a measure of yellow-blue discrimination, using an anomaloscope. The other predictors of significance were the degree of blood glucose control and the duration of diabetes. Although the predictions from a linear logistic model were significant in classifying the diabetic subjects into those whose fundus will remain normal and those in whom it will develop retinopathy, the number of misclassifications was substantial. An examination of the goodnessof fit between the data and the model suggested a criterion value (P) of around P = 0.3 for the probability that a patient develops retinopathy. At this value, the probability of being normal for an individual classed as normal was 0.82, and the probability ofdeveloping retinopathy for an individual classed as having retinopathy was 0.54.
Left Atrial Pressure Can Be Accurately Transmitted to the Pulmonary Artery despite Zone 1 Conditions
Authors: Richard K. Albert, Wayne J. E. Lamm
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Pulmonary arterial occlusion pressure is not thought to reflect left atrial pressure (Pla) when alveolar pressure (PA) exceeds pulmonary venous pressure because alveolar capillaries collapse and the required continuous fluid column between the pulmonary artery and left atrium is interrupted. However, arterial-to-venous flow can occur when PA exceeds both the pulmonary arterial pressure (Ppa) and pulmonary venous pressure (i.e., in Zone 1 conditions), indicating the existence of a continuous patent vascular channel. Accordingly, Ppa should reflect Pla under these conditions. To investigate this connection cannulas were placed in the pulmonary arteries and left atria of eight excised rabbit lungs. Ppa and Pla were set 5 cm H2O above PA, which ranged from 0 to 25 cm H2O. Pla was then reduced in 2 to 4 cm H2O decrements while recording Ppa when arterial-to-venous flow ceased. At all PAs greater than 0 cm H2O, Pla was accurately reflected by the Ppa when both were exceeded by PA. The greater the PA, the lower the Ppa could track Pla below PA. Pla can be accurately measured by a pulmonary arterial catheter under Zone 1 conditions.
TIE-2 and VEGFR Kinase Activities Drive Immunosuppressive Function of TIE-2–Expressing Monocytes in Human Breast Tumors
Authors: Mark Ibberson, Sylvian Bron, Nicolas Guex, Eveline Faes-van't Hull, Assia Ifticene-Treboux, Luc Henry, Hans-Anton Lehr, Jean-François Delaloye, George Coukos, Ioannis Xenarios, Marie-Agnès Doucey
Journal: Clinical Cancer Research (2013)

Tumor-associated TIE-2-expressing monocytes (TEM) are highly proangiogenic cells critical for tumor vascularization. We previously showed that, in human breast cancer, TIE-2 and VEGFR pathways control proangiogenic activity of TEMs. Here, we examine the contribution of these pathways to immunosuppressive activity of TEMs.We investigated the changes in immunosuppressive activity of TEMs and gene expression in response to specific kinase inhibitors of TIE-2 and VEGFR. The ability of tumor TEMs to suppress tumor-specific T-cell response mediated by tumor dendritic cells (DC) was measured in vitro. Characterization of TEM and DC phenotype in addition to their interaction with T cells was done using confocal microscopic images analysis of breast carcinomas.TEMs from breast tumors are able to suppress tumor-specific immune responses. Importantly, proangiogenic and suppressive functions of TEMs are similarly driven by TIE-2 and VEGFR kinase activity. Furthermore, we show that tumor TEMs can function as antigen-presenting cells and elicit a weak proliferation of T cells. Blocking TIE-2 and VEGFR kinase activity induced TEMs to change their phenotype into cells with features of myeloid dendritic cells. We show that immunosuppressive activity of TEMs is associated with high CD86 surface expression and extensive engagement of T regulatory cells in breast tumors. TIE-2 and VEGFR kinase activity was also necessary to maintain high CD86 surface expression levels and to convert T cells into regulatory cells.These results suggest that TEMs are plastic cells that can be reverted from suppressive, proangiogenic cells into cells that are able to mediate an antitumoral immune response.