tbuckley/cabot-search huggingface dataset:
Functions of Anti-MAGE T-Cells Induced in Melanoma Patients under Different Vaccination Modalities
Authors: Thierry Connerotte, Aline Van Pel, Danièle Godelaine, Eric Tartour, Beatrice Schuler-Thurner, Sophie Lucas, Kris Thielemans, Gerold Schuler, Pierre G. Coulie
Journal: Cancer Research (2008)

Abstract Tumor regressions have been observed in a small proportion of melanoma patients vaccinated with a MAGE-A3 peptide presented by HLA-A1, administered as peptide, ALVAC canarypox virus containing a MAGE-A3 minigene, or peptide-pulsed dendritic cells (DC). There was a correlation between tumor regression and the detection of anti–MAGE-3.A1 CTL responses. These responses were monoclonal and often of a very low magnitude after vaccination with peptide or ALVAC, and usually polyclonal and of a higher magnitude after DC vaccination. These results suggested that, at least in some patients, surprisingly few anti–MAGE-3.A1 T-cells could initiate a tumor regression process. To understand the role of these T cells, we carried out a functional analysis of anti–MAGE-3.A1 CTL clones derived from vaccinated patients who displayed tumor regression. The functional avidities of these CTL clones, evaluated in lysis assays, were surprisingly low, suggesting that high avidity was not part of the putative capability of these CTL to trigger tumor rejection. Most anti–MAGE-3.A1 CTL clones obtained after DC vaccination, but not after peptide or ALVAC vaccination, produced interleukin 10. Transcript profiling confirmed these results and indicated that approximately 20 genes, including CD40L, prostaglandin D2 synthase, granzyme K, and granzyme H, were highly differentially expressed between the anti–MAGE-3.A1 CTL clones derived from patients vaccinated with either peptide-ALVAC or peptide-pulsed DC. These results indicate that the modality of vaccination with a tumor-specific antigen influences the differentiation pathway of the antivaccine CD8 T-cells, which may have an effect on their capacity to trigger a tumor rejection response. [Cancer Res 2008;68(10):3931–40]
Effect of ambient ozone exposure on lung function in farm workers.
Authors: M Brauer, J Blair, S Vedal
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Effects of ozone exposure on outdoor farm workers in the Fraser Valley of British Columbia, Canada, were investigated. Fifty-eight workers underwent spirometry daily before and after each 8- to 14-h workday from June 23 to August 26, 1993. The mean daily maximum (1 h) ambient ozone concentration was 40 ppb (range: 13 to 84 ppb). Concentrations of acid aerosols and fine particulates, potential confounders of ozone effects, were very low. In individual regressions of evening FEV1 and FVC on maximum daily ozone concentration, 47 of 53 workers with valid data (46 of 53 for FVC) had negative slopes. The average slopes (weighted by the inverse SE of the regression coefficients) were -3.3 and -4.7 ml for FEV1 and FVC, respectively, for each ppb increase in ozone (p < 0.001). Following correction for an individual's mean lung function level, date, and temperature, regression of either the afternoon or the daily change (afternoon-morning) corrected for the morning measurement of FEV1 and FVC on ozone showed similar magnitudes of effect. These associations were still apparent on the following morning, suggesting a persistent ozone effect. These results indicate that exposure of a population of outdoor workers to ambient ozone concentrations below 85 ppb is associated with decreased lung function over the day, which persists to the following day.
The Importance of Race and Ethnic Background in Biomedical Research and Clinical Practice
Authors: Esteban González Burchard, Elad Ziv, Natasha Coyle, Scarlett Lin Gomez, Hua Tang, Andrew J. Karter, Joanna L. Mountain, Eliseo J. Pérez-Stable, Dean Sheppard, Neil Risch
Journal: New England Journal of Medicine (2003)

A debate has recently arisen over the use of racial classification in medicine and biomedical research. In particular, with the completion of a rough draft of the human genome, some have suggested that racial classification may not be useful for biomedical studies, since it reflects "a fairly small number of genes that describe appearance"1 and "there is no basis in the genetic code for race."2 In part on the basis of these conclusions, some have argued for the exclusion of racial and ethnic classification from biomedical research.3 In the United States, race and ethnic background have been used as cause . . .
Coronary Endothelial Dysfunction After Heart Transplantation Predicts Allograft Vasculopathy and Cardiac Death
Authors: Steven M. Hollenberg, Lloyd W. Klein, Joseph E. Parrillo, Markus Scherer, Durand Burns, Paul Tamburro, Monica Oberoi, Maryl R. Johnson, Maria Rosa Costanzo
Journal: Circulation (2001)

Background — Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development. Methods and Results — Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (&gt;50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-μg bolus), acetylcholine (54 μg over 2 minutes), and nitroglycerin (200 μg) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1±2.9% versus dilation of 1.7±2.2%, P =0.01) and microvascular (flow increase of 75±20% versus 149±16%, P =0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly. Conclusions — Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.
Patterns of prokaryotic lateral gene transfers affecting parasitic microbial eukaryotes
Authors: Cecilia Alsmark, Peter G Foster, Thomas Sicheritz-Ponten, Sirintra Nakjang, T Martin Embley, Robert P Hirt
Journal: Genome biology (2013)

Abstract Background The influence of lateral gene transfer on gene origins and biology in eukaryotes is poorly understood compared with those of prokaryotes. A number of independent investigations focusing on specific genes, individual genomes, or specific functional categories from various eukaryotes have indicated that lateral gene transfer does indeed affect eukaryotic genomes. However, the lack of common methodology and criteria in these studies makes it difficult to assess the general importance and influence of lateral gene transfer on eukaryotic genome evolution. Results We used a phylogenomic approach to systematically investigate lateral gene transfer affecting the proteomes of thirteen, mainly parasitic, microbial eukaryotes, representing four of the six eukaryotic super-groups. All of the genomes investigated have been significantly affected by prokaryote-to-eukaryote lateral gene transfers, dramatically affecting the enzymes of core pathways, particularly amino acid and sugar metabolism, but also providing new genes of potential adaptive significance in the life of parasites. A broad range of prokaryotic donors is involved in such transfers, but there is clear and significant enrichment for bacterial groups that share the same habitats, including the human microbiota, as the parasites investigated. Conclusions Our data show that ecology and lifestyle strongly influence gene origins and opportunities for gene transfer and reveal that, although the outlines of the core eukaryotic metabolism are conserved among lineages, the genes making up those pathways can have very different origins in different eukaryotes. Thus, from the perspective of the effects of lateral gene transfer on individual gene ancestries in different lineages, eukaryotic metabolism appears to be chimeric.
Accelerated Atherosclerosis, Aortic Aneurysm Formation, and Ischemic Heart Disease in Apolipoprotein E/Endothelial Nitric Oxide Synthase Double-Knockout Mice
Authors: Peter J. Kuhlencordt, Robert Gyurko, Fred Han, Marielle Scherrer-Crosbie, Thomas H. Aretz, Roger Hajjar, Michael H. Picard, Paul L. Huang
Journal: Circulation (2001)

Background To test whether deficiency in endothelial nitric oxide synthase (eNOS) affects atherosclerosis development, we compared lesion formation in apolipoprotein E (apoE)/eNOS-double knockout (DKO) and apoE-knockout (KO) control animals. Methods and Results After 16 weeks of “Western-type” diet, apoE/eNOS-DKO males and females showed significant increases in lesion area of 93.6% and 59.2% compared with apoE-KO mice. All apoE/eNOS-DKO animals studied developed peripheral coronary arteriosclerosis, associated with perivascular and myocardial fibrosis, whereas none of the apoE-KO mice did. Transthoracic echocardiography showed a significantly increased left ventricular wall thickness and decreased fractional shortening in DKO animals. Mean arterial pressure was increased in DKO mice and was comparable in degree to eNOS-KO animals. Male DKO animals developed atherosclerotic abdominal aneurysms and aortic dissection. Conclusions eNOS deficiency increases atherosclerosis in Western-type diet-fed apoE-KO animals and introduces coronary disease and an array of cardiovascular complications, including spontaneous aortic aneurysm and dissection. This phenotype constitutes the first murine model to demonstrate distal coronary arteriosclerosis associated with evidence of myocardial ischemia, infarction, and heart failure. Hypertrophy and reduced left ventricular function cannot be explained by increased blood pressure alone, because eNOS-KO animals do not develop these complications.
Food Intake Enhances Thromboxane Receptor–Mediated Platelet Activation in Type 2 Diabetic Patients but Not in Healthy Subjects
Authors: Masoud Razmara, Paul Hjemdahl, Marianne Yngen, Claes-Göran Östenson, N. Håkan Wallén, Nailin Li
Journal: Diabetes Care (2006)

Diabetes is associated with platelet hyperactivity (1,2), increases in circulating activated platelets and platelet-leukocyte aggregates (PLAs), and platelet hyperreactivity to in vitro stimulation (2,3). Thromboxane-mediated platelet activation is of special interest since diabetes is associated with increased platelet-dependent thromboxane A2 (TxA2) production (2), and diabetic patients appear to benefit less from prevention with aspirin than nondiabetic patients (4,5).

Insufficient insulin production and/or insulin resistance in diabetes leads to hyperglycemia, especially after food intake. Accumulating evidence indicates that postprandial hyperglycemia contributes to diabetes cardiovascular complications and may even predict complications more closely than fasting glucose levels (6). We recently reported (7) the effects of food intake and oral antidiabetes treatment on platelet function in type 2 diabetic patients. We found that food intake augmented platelet activation stimulated by ADP but not by thrombin (7). Responses to the TxA2 analog U46619 were also studied but have not been reported. Healthy control subjects were only studied in the fasting state in the original study design (7). We therefore recalled them to test if the meal causes similar enhancement of platelet activation in subjects with normal blood glucose regulation, and we currently focus on the responsiveness to U46619.

Fifteen patients with fairly well-controlled type 2 diabetes (mean ± SE age 53 ± 6 years, 11 male and 4 female, BMI 28.1 ± 3.8 kg/m2, A1C 6.8 ± 1.7% [reference <5.2%]). The study originally recruited 15 matched healthy control subjects, but only 10 (age 51 …
PROTEIN METABOLISM AND EXCHANGE AS INFLUENCED BY CONSTRICTION OF THE VENA CAVA
Authors: Frank W. McKee, Paul R. Schloerb, John A. Schilling, Garson H. Tishkoff, George H. Whipple
Journal: The Journal of Experimental Medicine (1948)

Constriction of inferior vena cava above the diaphragm is used to produce experimental ascites in the dog. This type of experimental ascites drains the body protein reserves, reduces the level of circulating plasma proteins, and in effect is an internal plasmapheresis. As the ascitic fluid is withdrawn and the proteins measured, we observe a production of ascitic protein (80-90 gm. per week) comparable to that removed by plasmapheresis (bleeding and replacement of red cells in saline). High protein diet tends to decrease the ascites but the protein content of the ascitic fluid may increase. Sodium chloride increases notably the volume of the ascites which accumulates and the total ascitic protein output increases. Sodium-free salt mixtures have a negative influence. High protein diet low in sodium salts gives minimal ascitic accumulation under these conditions. The question of circulation of the ascitic fluid is raised-how rapid is the absorption and the related accumulation?
THE COLONY MORPHOLOGY OF TUBERCLE BACILLI
Authors: Kenneth C. Smithburn
Journal: The Journal of Experimental Medicine (1936)

The colony topography of tubercle bacilli is significantly affected by altering the pH of the culture medium on which the organisms are grown. Under the conditions of these experiments, avian tubercle bacilli produce two variants, rough and smooth. The former are most numerous on the most acid medium used (pH 6.0); the smooth colonies are obtained over a broad range of pH. Three colonial variants of bovine and human tubercle bacilli are described. Both mammalian types produce greater numbers of rough colonies at pH 6.0. The bovine type strains produce greatest numbers of smooth colonies in the pH range 6.4 to 6.8, and intermediate colonies on alkaline medium. The human type strains produce greatest numbers of smooth colonies at pH 6.4 and large numbers of intermediate colonies at pH 6.8 and pH 7.2. Included among the avian and bovine strains studied are organisms of widely varying pathogenic properties. Virulent and attenuated strains of a given type produce similar colonial variants under similar environmental conditions.
Synovial fluid phospholipase A2s and inflammation.
Authors: H Gonzalez-Buritica, M.A Khamashita, G.R Hughes
Journal: Annals of the Rheumatic Diseases (1989)

The activation of phospholipase A2 is believed to have an important role in the inflammatory process owing to its induction of eicosanoids, platelet activating factor, and other mediators. Soluble phospholipase A2 has been associated with exudates in different inflammatory conditions. In this review the general physiology and control of this enzyme and, in particular, the most recent findings on human synovial fluid phospholipase A2s are discussed.
Hyaluronic Acid Synthase-1 Expression Regulates Bladder Cancer Growth, Invasion, and Angiogenesis through CD44
Authors: Roozbeh Golshani, Luis Lopez, Veronica Estrella, Mario Kramer, Naoko Iida, Vinata B. Lokeshwar
Journal: Cancer Research (2008)

Abstract Hyaluronic acid (HA) promotes tumor metastasis and is an accurate diagnostic marker for bladder cancer. HA is synthesized by HA synthases HAS1, HAS2, or HAS3. We have previously shown that HAS1 expression in tumor tissues is a predictor of bladder cancer recurrence and treatment failure. In this study, we stably transfected HT1376 bladder cancer cells with HAS1-sense (HAS1-S), HAS1-antisense (HAS1-AS), or vector cDNA constructs. Whereas HAS1-S transfectants produced ∼1.7-fold more HA than vector transfectants, HA production was reduced by ∼70% in HAS1-AS transfectants. HAS1-AS transfectants grew 5-fold slower and were ∼60% less invasive than vector and HAS1-S transfectants. HAS1-AS transfectants were blocked in G2-M phase of the cell cycle due to down-regulation of cyclin B1, cdc25c, and cyclin-dependent kinase 1 levels. These transfectants were also 5- to 10-fold more apoptotic due to the activation of the Fas-Fas ligand–mediated extrinsic pathway. HAS1-AS transfectants showed a ∼4-fold decrease in ErbB2 phosphorylation and down-regulation of CD44 variant isoforms (CD44-v3, CD44-v6, and CD44-E) both at the protein and mRNA levels. However, no decrease in RHAMM levels was observed. The decrease in CD44-v mRNA levels was not due to increased mRNA degradation. Whereas CD44 small interfering RNA (siRNA) transfection decreased cell growth and induced apoptosis in HT1376 cells, HA addition modestly increased CD44 expression and cell growth in HAS1-AS transfectants, which could be blocked by CD44 siRNA. In xenograft studies, HAS1-AS tumors grew 3- to 5-fold slower and had ∼4-fold lower microvessel density. These results show that HAS1 regulates bladder cancer growth and progression by modulating HA synthesis and HA receptor levels. [Cancer Res 2008;68(2):483–91]
A martial arts injury: karate induced unilateral haematoma of the adrenal gland * Commentary
Authors: M Ortu, M Vaccarezza, S Trovati, M Galli, C Gervasoni
Journal: British Journal of Sports Medicine (2006)

Adrenal gland haematoma is often a complication of traumatic events. The case is reported of a 45 year old man with unilateral non-symptomatic adrenal gland haematoma caused by a trauma during martial arts practice.
Single Nucleotide Polymorphisms in the <i>NOD2/CARD15</i> Gene Are Associated With an Increased Risk of Relapse and Death for Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation With Unrelated Donors
Authors: Neema P. Mayor, Bronwen E. Shaw, Derralynn A. Hughes, Hazael Maldonado-Torres, J. Alejandro Madrigal, Satish Keshav, Steven G.E. Marsh
Journal: Journal of Clinical Oncology (2007)

Purpose Hematopoietic stem cell transplantation (HSCT) is an important option in the management of acute leukemia, but the risk of disease relapse and death remains appreciable. Recent studies have suggested that nucleotide-binding oligomerization domain 2 (NOD2)/caspase recruitment domain 15 (CARD15) gene single nucleotide polymorphisms (SNPs), implicated in innate immunity and Crohn's disease, may also affect immune function post-HSCT. Patients and Methods NOD2/CARD15 genotypes were analyzed in 196 patients diagnosed with acute leukemia and their unrelated donors. The pairs are part of a previously well-characterized cohort with a median follow-up of 2.2 years (range, 0.42 to 6.61 years). T-cell depletion was used in 83% of pairs. Results NOD2/CARD15 SNPs were associated with a reduction in overall survival (44% v 22%; log-rank P = .0087) due to an increase in disease relapse (32% v 54%; Gray's test P = .001) as compared with wild-type pairs. In multivariate analyses, the two most significant factors impacting outcome were transplantation in relapse and the presence of SNPs. The incidence of acute graft-versus-host disease was low and there was no significant difference due to the presence of SNPs. Conclusion These data indicate an unrecognized role for the NOD2/CARD15 gene in unrelated donor HSCT for acute leukemia. The increased risk of disease relapse suggests that the wild-type gene product may contribute to a graft-versus-leukemia effect. These data suggest that NOD2/CARD15 genotyping before transplantation may contribute to prognosis and influence clinical management.
Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family.
Authors: M G Tonnesen, D C Anderson, T A Springer, A Knedler, N Avdi, P M Henson
Journal: Journal of Clinical Investigation (1989)

The process of neutrophil adhesion to and migration through the microvascular endothelium, an early event in the induction of the acute inflammatory response, has been attributed to the generation of extravascular chemoattractants. Although both chemotactic peptides and lipid mediators enhance neutrophil adherence in vitro and in vivo, the mechanism(s) involved in the interaction between circulating neutrophils and microvascular endothelial cells is still not completely understood. In a microtiter well adherence assay, the chemotactic peptides, FMLP and C5a, and the lipid mediators, leukotriene B4 (LTB4) and platelet activating factor (PAF), enhanced human neutrophil adherence to cultured human microvascular endothelial cells as well as to human umbilical vein endothelial cells in a dose-dependent manner with a rapid time course. This stimulated adhesive interaction between neutrophils and cultured human endothelial cells was dependent on the expression of the Mac-1, LFA-1, p150,95 glycoprotein family on the neutrophil surface since neutrophils from patients with leukocyte adhesion deficiency, lacking surface expression of the adhesive glycoproteins, exhibited markedly diminished adherence to human endothelial cells in response to stimulation with chemotactic factors compared to normal control neutrophils. All four mediators enhanced expression of the glycoprotein family on the surface of normal neutrophils as determined by flow cytofluorimetry using a monoclonal antibody (TS1/18) to the glycoprotein common beta subunit. In addition, TS1/18 inhibited up to 100% the adherence of normal neutrophils to endothelial cells stimulated by maximal concentrations of FMLP, C5a, LTB4, or PAF. Moreover, HL-60 cells, human promyelocytic leukemia cells, neither increased glycoprotein surface expression nor adherence in response to stimulation. Thus, peptide and lipid mediators of the acute inflammatory response appear to enhance adherence of circulating neutrophils to the microvascular endothelium by a mechanism dependent on expression of the Mac-1, LFA-1, p150,95 glycoprotein family on the neutrophil surface.
Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function
Authors: Makoto Yawata, Nobuyo Yawata, Monia Draghi, Ann-Margaret Little, Fotini Partheniou, Peter Parham
Journal: The Journal of Experimental Medicine (2006)

Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands regulate the development and response of human natural killer (NK) cells. Natural selection drove an allele-level group A KIR haplotype and the HLA-C1 ligand to unusually high frequency in the Japanese, who provide a particularly informative population for investigating the mechanisms by which KIR and HLA polymorphism influence NK cell repertoire and function. HLA class I ligands increase the frequencies of NK cells expressing cognate KIR, an effect modified by gene dose, KIR polymorphism, and the presence of other cognate ligand–receptor pairs. The five common Japanese KIR3DLI allotypes have distinguishable inhibitory capacity, frequency of cellular expression, and level of cell surface expression as measured by antibody binding. Although KIR haplotypes encoding 3DL1*001 or 3DL1*005, the strongest inhibitors, have no activating KIR, the dominant haplotype encodes a moderate inhibitor, 3DL1*01502, plus functional forms of the activating receptors 2DL4 and 2DS4. In the population, certain combinations of KIR and HLA class I ligand are overrepresented or underrepresented in women, but not men, and thus influence female fitness and survival. These findings show how KIR–HLA interactions shape the genetic and phenotypic KIR repertoires for both individual humans and the population.