tbuckley/cabot-search huggingface dataset:
Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Human Dendritic Cells
Authors: Helmut Jonuleit, Edgar Schmitt, Gerold Schuler, Jürgen Knop, Alexander H. Enk
Journal: The Journal of Experimental Medicine (2000)

The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83(-) and mature CD83(+) human DCs were used for stimulation of naive, allogeneic CD4(+) T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte-associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon gamma, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10-producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10-producing T cell regulatory 1-like cells by immature DCs.
A Contribution to the Pathology of the Rheumatoid Type of Arthritis and of Rheumatic Fever (Abstract)
Authors: A. G. T. Fisher
Journal: Annals of the Rheumatic Diseases (1939)

OUR knowledge of the pathological changes in the rheumatoid type of arthritis of so-called " unknown vetiology " (synonyms: rheumatoid, atrophic and proliferative arthritis) has been hitherto founded chiefly upon the descriptions of Nichols and Richardson (1910), Strangeways (1918), and others.It is important to realise, however, that these observations are largely based upon investigations in the later stages of the disease, or even the stage of " sequels."The rheumatoid type of arthritis is rarely fatal per se, so that opportunities for investigation of the pathological changes in the earlier or acute stages seldom occur, and many of the existing pathological descriptions are based upon post-mortem examinations of elderly sufferers who have died of some intercurrent disease and in which the essential pathological features have become obscured by secondary osteo-arthritic or other changes.The same criticism applies to material hitherto obtained at operation, since there were few indications for surgery in the active stages of rheumatoid disease.Post-mortem exam- inations of patients who have succumbed to rheumatic fever are, of course, frequently performed, but few would deny that the changes in the joints in such cases have not received the con- sideration that they deserve. SOURCE OF MATERIALThe author has found that the operation of arthrotomy followed by lavage with an antiseptic solution is of great value in certain acute or subacute forms of arthritis of the rheumatoid type, particularly when such large and comparatively superficial joints as the knee are principally affected.In some subacute cases, partial synovectomy has been performed.The results in the * Discussion on the -,tiology of Acute Rheumatism and Rheumatoid
Augmented Pulmonary Responses to Acute Ozone Exposure in Obese Mice: Roles of TNFR2 and IL-13
Authors: Alison Suzanne Williams, Joel Andrew Mathews, David Itiro Kasahara, Lucas Chen, Allison Patricia Wurmbrand, Huiqing Si, Stephanie Ann Shore
Journal: Environmental Health Perspectives (2013)

Acute ozone (O(3)) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice.We examined the hypothesis that these augmented responses to O(3) are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13.We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2(-/-)) mice, and obese Cpe(fat) and TNFR2-deficient Cpe(fat) mice (Cpe(fat)/TNFR2(-/-)), to O(3) (2 ppm for 3 hr) either with or without treatment with anti-IL-13 or left them unexposed.O(3)-induced increases in baseline pulmonary mechanics, airway responsiveness, and cellular inflammation were greater in Cpe(fat) than in WT mice. In lean mice, TNFR2 deficiency ablated O(3)-induced AHR without affecting pulmonary inflammation; whereas in obese mice, TNFR2 deficiency augmented O(3)-induced AHR but reduced inflammatory cell recruitment. O(3) increased pulmonary expression of IL-13 in Cpe(fat) but not WT mice. Flow cytometry analysis of lung cells indicated greater IL-13-expressing CD(4+) cells in Cpe(fat) versus WT mice after O(3) exposure. In Cpe(fat) mice, anti-IL-13 treatment attenuated O(3)-induced increases in pulmonary mechanics and inflammatory cell recruitment, but did not affect AHR. These effects of anti-IL-13 treatment were not observed in Cpe(fat)/TNFR2(-/-) mice. There was no effect of anti-IL-13 treatment in WT mice.Pulmonary responses to O(3) are not just greater, but qualitatively different, in obese versus lean mice. In particular, in obese mice, O(3) induces IL-13 and IL-13 synergizes with TNF via TNFR2 to exacerbate O(3)-induced changes in pulmonary mechanics and inflammatory cell recruitment but not AHR.
Improvement of diagnosis in the non-invasive assessment of coronary artery disease: enhanced evaluation of quantitative exercise 201thallium imaging by multivariate analysis
Authors: M. G Niemeyer, A. H Zwinderman, M. J Cramer, E. E van der Wall, F. J Verzijlbergen, A. Breeman, C. A Ascoop, E. K J Pauwels
Journal: Cardiovascular Research (1990)

Study objective – The aim was to evaluate discriminant analysis, performed in patients without prior myocardial infarction, in enhancing the diagnostic value of quantitative exercise 201thallium scintigraphy. Design – All clinical, electrocardiographic, and scintigraphic variables were first subjected to a univariate analysis. Afterwards a discriminant analysis was done. Patients – 135 patients (104 male) were studied. Age was 24-70 years, mean 55 years. Measurements and main results – Two discriminant analyses were done. In the first analysis, the ability to detect the presence of coronary artery disease was tested. Significant variables were: (1) history of angina, (2) sex, (3) quantitative analysis of 201thallium scintigraphy, (4) age, (5) ischaemic ST response, (6) angina during the test, and (7) the pressure-rate product. The sensitivity, specificity, and accuracy of classification using the discriminant function were 91%, 87%, and 90%, respectively. The sensitivity was higher than when using only visual interpretation (sensitivity 70%; p<0.0002) or quantitative interpretation (sensitivity = 66%; p<0.000l) of thallium scans, without significant loss of specificity (p<0.5488; p<0.6875). In the second analysis, a discriminant function was calculated to detect multivessel disease. Five input variables were selected: (1) number of vessels with stenosis predicted by quantitative analysis, (2) number of vessels with stenosis predicted by visual analysis, (3) ischaemic ST response, (4) sex, (5) angina during the test. Multivariate analysis showed an increase in sensitivity when compared with visual interpretation (78% v 55%; p<0.0043) and quantitative analysis (66%; p<0.0156). Using the classification, the discriminant function was more accurate than visual analysis (81% v 69%) or quantitative analysis (77%). Conclusions – The results show that multivariate analysis of non-invasive test results in quantitative thallium exercise testing allows convenient use for clinical purposes with improved results.
Immune mechanisms in leukemia role of the Ia antigens.
Authors: O A Lukasewycz, J A Frelinger
Journal: The Journal of Experimental Medicine (1977)

We have shown that the selective removal of cells possessing Ia determinants coded by the I-A, I-B, and I-J regions of the H-2 gene complex completely abrogates the protective capacity of nylon-wool-purified T lymphocytes against leukemic challenge. This suggests that the Ia antigen bearing T cells play an important role in tumor immunity.
Health professionals' and service users' interpretation of screening test results: experimental study
Authors: Ros Bramwell, Helen West, Peter Salmon
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To investigate the accuracy of interpretation of probabilistic screening information by different stakeholder groups and whether presentation as frequencies improves accuracy. <b>Design</b> Between participants experimental design; participants responded to screening information embedded in a scenario. <b>Setting</b> Regional maternity service and national conferences and training days. <b>Participants</b> 43 pregnant women attending their first antenatal appointment in a regional maternity service; 40 companions accompanying the women to their appointments; 42 midwives; 41 obstetricians. Participation rates were 56%, 48%, 89%, and 71% respectively. <b>Measures</b> Participants estimated the probability that a positive screening test result meant that a baby actually had Down9s syndrome on the basis of all the relevant information, which was presented in a scenario. They were randomly assigned to scenarios that presented the information in percentage (n = 86) or frequency (n = 83) format. They also gave basic demographic information and rated their confidence in their estimate. <b>Results</b> Most responses (86%) were incorrect. Obstetricians gave significantly more correct answers (although still only 43%) than either midwives (0%) or pregnant women (9%). Overall, the proportion of correct answers was higher for presentation as frequencies (24%) than for presentation as percentages (6%), but further analysis showed that this difference occurred only in responses from obstetricians. Many health professionals were confident in their incorrect responses. <b>Conclusions</b> Most stakeholders in pregnancy screening draw incorrect inferences from probabilistic information, and health professionals need to be aware of the difficulties that both they and their patients have with such information. Moreover, they should be aware that different people make different mistakes and that ways of conveying information that help some people will not help others.
PARma: identification of microRNA target sites in AGO-PAR-CLIP data
Authors: Florian Erhard, Lars Dölken, Lukasz Jaskiewicz, Ralf Zimmer
Journal: Genome biology (2013)

PARma is a complete data analysis software for AGO-PAR-CLIP experiments to identify target sites of microRNAs as well as the microRNA binding to these sites. It integrates specific characteristics of the experiments into a generative model. The model and a novel pattern discovery tool are iteratively applied to data to estimate seed activity probabilities, cluster confidence scores and to assign the most probable microRNA. Based on differential PAR-CLIP analysis and comparison to RIP-Chip data, we show that PARma is more accurate than existing approaches. PARma is available from http://www.bio.ifi.lmu.de/PARma
Brain-Reactive Antibodies and Disease
Authors: B. Diamond, G. Honig, S. Mader, L. Brimberg, B.T. Volpe
Journal: Annual Review of Immunology (2013)

Autoimmune diseases currently affect 5–7% of the world's population; in most diseases there are circulating autoantibodies. Brain-reactive antibodies are present in approximately 2–3% of the general population but do not usually contribute to brain pathology. These antibodies penetrate brain tissue only early in development or under pathologic conditions. This restriction on their pathogenicity and the lack of correlation between serum titers and brain pathology have, no doubt, contributed to a delayed appreciation of the contribution of autoantibodies in diseases of the central nervous system. Nonetheless, it is increasingly clear that antibodies can cause damage in the brain and likely initiate or aggravate multiple neurologic conditions; brain-reactive antibodies contribute to symptomatology in autoimmune disease, infectious disease, and malignancy.
Sensitivity to temozolomide in brain tumor initiating cells
Authors: M. D. Blough, M. R. Westgate, D. Beauchamp, J. J. Kelly, O. Stechishin, A. L. Ramirez, S. Weiss, J. G. Cairncross
Journal: Neuro-Oncology (2010)

Molecular alterations in glioblastoma have the potential to guide treatment. Here, we explore the relationship between temozolomide (TMZ) response and O6-methylguanine DNA methyltransferase (MGMT) status in brain tumor initiating cells (BTICs). Methylation, expression, and sensitivity were assessed in 20 lines; associations were evaluated by Fisher's exact test. Some BTICs were sensitive. Sensitivity to TMZ was only associated with protein expression (P = .001). There were atypical BTICs including TMZ-resistant lines in which the methylation-specific PCR reaction revealed both methylated and unmethylated bands. BTICs are not uniformly resistant to TMZ; some are sensitive. MGMT status does not predict TMZ response with high precision.
Malignant mesothelioma after radiation treatment for Hodgkin lymphoma
Authors: Marie L. De Bruin, Jacobus A. Burgers, Paul Baas, Mars B. van 't Veer, Evert M. Noordijk, Marieke W. J. Louwman, Josée M. Zijlstra, Hendrik van den Berg, Berthe M. P. Aleman, Flora E. van Leeuwen
Journal: Blood (2009)
Epidemic Clones, Oceanic Gene Pools, and Eco-LD in the Free Living Marine Pathogen Vibrio parahaemolyticus
Authors: Yujun Cui, Xianwei Yang, Xavier Didelot, Chenyi Guo, Dongfang Li, Yanfeng Yan, Yiquan Zhang, Yanting Yuan, Huanming Yang, Jian Wang, Jun Wang, Yajun Song, Dongsheng Zhou, Daniel Falush, Ruifu Yang
Journal: Molecular Biology and Evolution (2015)

We investigated global patterns of variation in 157 whole-genome sequences of Vibrio parahaemolyticus, a free-living and seafood associated marine bacterium. Pandemic clones, responsible for recent outbreaks of gastroenteritis in humans, have spread globally. However, there are oceanic gene pools, one located in the oceans surrounding Asia and another in the Mexican Gulf. Frequent recombination means that most isolates have acquired the genetic profile of their current location. We investigated the genetic structure in the Asian gene pool by calculating the effective population size in two different ways. Under standard neutral models, the two estimates should give similar answers but we found a 27-fold difference. We propose that this discrepancy is caused by the subdivision of the species into a hundred or more ecotypes which are maintained stably in the population. To investigate the genetic factors involved, we used 51 unrelated isolates to conduct a genome-wide scan for epistatically interacting loci. We found a single example of strong epistasis between distant genome regions. A majority of strains had a type VI secretion system associated with bacterial killing. The remaining strains had genes associated with biofilm formation and regulated by cyclic dimeric GMP signaling. All strains had one or other of the two systems and none of isolate had complete complements of both systems, although several strains had remnants. Further “top down” analysis of patterns of linkage disequilibrium within frequently recombining species will allow a detailed understanding of how selection acts to structure the pattern of variation within natural bacterial populations.
Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial
Authors: Frank Thies, Jennifer MC Garry, Parveen Yaqoob, Kittipan Rerkasem, Jennifer Williams, Cliff P Shearman, Patrick J Gallagher, Philip C Calder, Robert F Grimble
Journal: The Lancet (2003)
Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-κB
Authors: A.Z. Badrichani, D.M. Stroka, G. Bilbao, D.T. Curiel, F.H. Bach, C. Ferran
Journal: Journal of Clinical Investigation (1999)

To maintain the integrity of the vascular barrier, endothelial cells (EC) are resistant to cell death. The molecular basis of this resistance may be explained by the function of antiapoptotic genes such as bcl family members. Overexpression of Bcl-2 or Bcl-XL protects EC from tumor necrosis factor (TNF)-mediated apoptosis. In addition, Bcl-2 or Bcl-XL inhibits activation of NF-kappaB and thus upregulation of proinflammatory genes. Bcl-2-mediated inhibition of NF-kappaB in EC occurs upstream of IkappaBalpha degradation without affecting p65-mediated transactivation. Overexpression of bcl genes in EC does not affect other transcription factors. Using deletion mutants of Bcl-2, the NF-kappaB inhibitory function of Bcl-2 was mapped to bcl homology domains BH2 and BH4, whereas all BH domains were required for the antiapoptotic function. These data suggest that Bcl-2 and Bcl-XL belong to a cytoprotective response that counteracts proapoptotic and proinflammatory insults and restores the physiological anti-inflammatory phenotype to the EC. By inhibiting NF-kappaB without sensitizing the cells (as with IkappaBalpha) to TNF-mediated apoptosis, Bcl-2 and Bcl-XL are prime candidates for genetic engineering of EC in pathological conditions where EC loss and unfettered activation are undesirable.
Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation
Authors: Patricia A. Sheiner, Myron E. Schwartz, Eytan Mor, Leona K. Schluger, Neil Theise, Keiji Kishikawa, Vadim Kolesnikov, Henry Bodenheimer, Sukru Emre, Charles M. Miller
Journal: Hepatology (1995)

Recurrent hepatitis C causes significant morbidity after liver transplantation. Because immunosuppression is associated with enhanced viral replication, we postulated that clinical recurrence of the disease may be associated with augmented immunosuppression for rejection. In 96 patients with hepatitis C who received liver transplants, we recorded the interval from transplantation to recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the number of rejection episodes, and the use of OKT3 induction. Recurrence was diagnosed based on elevated transaminases and characteristic histology. Hepatitis C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously had SRR hadrecurrence, versus 28 of 75 patients (37.3%) who either had no SRR (72 patients) or had it after recurrence was diagnosed (3 patients) (P <.01). Mean time to recurrence was 127 ± 31 days in the 15 patients who had had SRR versus 246 ± 42 days in the other 28 patients (P = 0.02). Recurrence and number of rejection episodes were clearly associated: 6 of 33 patients (18.2%) with no rejection had recurrence (P<.05), versus 11 of 26 patients (42.3%) with one rejection episode (P<.05) and 26 of 37 (70.2%) with more than 1 episode (P<.05). OKT3 induction was used in 15 patients; 9 of 15 patients had recurrence (ns) at 337 ± 95 days. Of 72 patients who initially received triple immunosuppression, 30 patients had recurrence at 186 ± 25 days (P = 0.05). Nine patients received primary FK506; 4 had recurrence at 68 ± 14 days. SRR requiring OKT3 is associated with a higher incidence and earlier presentation of recurrent hepatitis C. Multiple rejection episodes are also associated with a higher recurrence rate. Induction immunotherapy, by reducing the rate of early rejection, may delay the clinical recurrence of hepatitis C. (Hepatology 1995;21:30-34).
Systemic inflammatory response after bronchoalveolar lavage in critically ill patients
Authors: T.T. Bauer, C. Arosio, C. Montón, X. Filella, A. Xaubet, A. Torres
Journal: European Respiratory Journal (2001)

Bronchoscopic bronchoalveolar lavage (BAL) may be followed by a systemic inflammatory response. Previous reports have suggested pneumonia as a predisposing condition and systemic cytokines as possible mediators. To test this hypothesis, systemic levels of interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were studied before and at 12 h and 24 h after bronchoscopically guided BAL in 30 mechanically ventilated patients (median age 67 (range 54–76) yrs, simplified acute physiology score II (SAPS II) 33 (12–56)), 20 of whom had pneumonia and 10 of whom were control patients without pneumonia. Arterial oxygen partial pressure to inspired oxygen fraction ratio ( P a,O 2 / F I,O 2 ), body temperature, mean arterial pressure, and cardiac frequency were recorded. The majority of patients (28/30, 93%) received antibiotic treatment prior to the procedure. P a,O 2 / F I,O 2 ratio was lower at 12 h compared to baseline in patients with pneumonia (baseline median 192 (range 65–256); 12 h 160 (66–190) mmHg, p&lt;0.001) and ventilated controls (baseline 293 (205–473); 12 h 226 (153–330) mm Hg p=0.011), but returned to baseline levels at 24 h (pneumonia: 194 (92–312), p=0.991; controls: 309 (173–487) mmHg, p=0.785). No changes in other clinical variables were observed. Systemic TNF-α levels before BAL (pneumonia: 35 (10–88); controls: 17 (0–33) pg·mL −1 ) did not increase at 12 h (pneumonia: 35 (0–64); p=0.735; controls: 16 (0–21) pg·mL −1 , p=0.123 comparison to baseline) or 24 h (pneumonia: 31 (0–36), p=0.464; controls: 19 (0–43) pg·mL −1 , p=0.358). No changes of IL-1β (baseline: pneumonia 0 (0–13); controls 1 (0–32) pg·mL −1 ) or IL-6 (baseline: pneumonia, 226 (9–4300); controls, 53 (0–346) pg·mL −1 ) were detected. No deterioration of clinical variables and no increase in systemic cytokine release has been observed after bronchoalveolar lavage, in critically ill patients. The potential cytokine increase is probably too small, in relation to the pre-existing inflammatory response, to yield clinical significance in this population otherwise antibiotic therapy may have been protective.
Statin-Sensitive Dysregulated AT1 Receptor Function and Density in Hypercholesterolemic Men
Authors: Georg Nickenig, Anselm T. Bäumer, Yavuz Temur, Daniela Kebben, Friedrich Jockenhövel, Michael Böhm
Journal: Circulation (1999)

Background —Hypercholesterolemia causes an upregulation of vascular angiotensin II type 1 (AT1) receptor expression in cell culture and animal models. The presented studies were undertaken to examine AT1 receptor overexpression in hypercholesterolemic men and therapeutic interventions thereof by HMG CoA reductase inhibitors (statins). Methods and Results —Effects of AT1 receptor activation were measured by assessing the blood pressure increase after infusion of angiotensin II in normo- (cholesterol 181±11 mg/dL) and hypercholesterolemic (cholesterol 294±10 mg/dL) men (n=19 and 20, respectively). AT1 receptor expression was assessed on isolated platelets. Some patients were investigated before and after cholesterol-lowering therapy with statins. Hypercholesterolemia led to a significant increase of angiotensin II-induced blood pressure elevation. AT1 receptor expression was significantly enhanced in hypercholesterolemic individuals (B max =5.2±1.2 fmol/mg protein) compared with normocholesterolemic men (B max =2.1±0.2 fmol/mg protein). Cholesterol-lowering treatment with statins reversed the elevated blood pressure response to angiotensin II infusion ( P &lt;0.05) and downregulated AT1 receptor density ( P &lt;0.05). Conclusions —Hypercholesterolemia induces AT1 receptor overexpression and enhances biological effects of angiotensin II in men. These findings provide novel insights into the pathogenesis of hypertension and atherosclerosis and may initiate rational and new therapeutic concepts.