tbuckley/cabot-search huggingface dataset:
Interleukin-17 is a negative regulator of established allergic asthma
Authors: Silvia Schnyder-Candrian, Dieudonnée Togbe, Isabelle Couillin, Isabelle Mercier, Frank Brombacher, Valérie Quesniaux, Francois Fossiez, Bernhard Ryffel, Bruno Schnyder
Journal: The Journal of Experimental Medicine (2006)

T helper (Th)17 cells producing interleukin (IL)-17 play a role in autoimmune and allergic inflammation. Here, we show that IL-23 induces IL-17 in the lung and IL-17 is required during antigen sensitization to develop allergic asthma, as shown in IL-17R–deficient mice. Since IL-17 expression increased further upon antigen challenge, we addressed its function in the effector phase. Most strikingly, neutralization of IL-17 augmented the allergic response in sensitized mice. Conversely, exogenous IL-17 reduced pulmonary eosinophil recruitment and bronchial hyperreactivity, demonstrating a novel regulatory role of IL-17. Mechanistically, IL-17 down modulated eosinophil-chemokine eotaxin (CCL11) and thymus- and activation-regulated chemokine/CCL17 (TARC) in lungs in vivo and ex vivo upon antigen restimulation. In vitro, IL-17 reduced TARC production in dendritic cells (DCs)—the major source of TARC—and antigen uptake by DCs and IL-5 and IL-13 production in regional lymph nodes. Furthermore, IL-17 is regulated in an IL-4–dependent manner since mice deficient for IL-4Rα signaling showed a marked increase in IL-17 concentration with inhibited eosinophil recruitment. Therefore, endogenous IL-17 is controlled by IL-4 and has a dual role. Although it is essential during antigen sensitization to establish allergic asthma, in sensitized mice IL-17 attenuates the allergic response by inhibiting DCs and chemokine synthesis.
Inhibitors of Arterial Relaxation Among Components of Human Oxidized Low-Density Lipoproteins
Authors: Vale´rie Deckert, Laurence Perse´gol, Laurence Viens, Ge´rard Lizard, Anne Athias, Christian Lallemant, Philippe Gambert, Laurent Lagrost
Journal: Circulation (1997)

Oxidized low-density lipoproteins (LDLs) are known to impair arterial relaxation. The aim of the present study was to identify the components of oxidized LDL that may account for inhibition of endothelium-dependent relaxation.LDLs from 12 healthy subjects were either maintained at 4 degrees C (native LDL) or incubated at 37 degrees C in the presence of copper sulfate (oxidized LDL). Unlike pretreatment with native LDL, pretreatment with oxidized LDL reduced significantly the acetylcholine-mediated relaxation of rabbit aortic segments compared with control segments incubated in Krebs' buffer (maximal relaxation [Emax], 72.0 +/- 6.7% versus 94.1 +/- 0.8%, respectively, P < .01; negative logarithm of the concentration required to produce a half-maximal relaxing effect [pD2], 6.6 +/- 0.1 versus 7.2 +/- 0.1, respectively, P < .001). The absolute difference between Emax values obtained with oxidized and native LDL (delta Emax) correlated significantly with the formation of 7 ketocholesterol, 7 alpha-hydroxycholesterol, and 7 beta-hydroxy-cholesterol. In contrast, delta Emax did not correlate with the amount of lipoperoxides or lysophosphatidylcholine formed, and the difference of pD2 values measured with oxidized and native LDL (delta pD2) did not correlate significantly with any of the oxidation-derived LDL compounds. When added individually, 7-ketocholesterol and 7 beta-hydroxycholesterol reduced Emax values but not pD2 values in a time- and concentration-dependent manner.Cholesterol derivatives in oxidized LDL can reduce maximal arterial relaxation through a specific effect on vascular endothelial cells.
Regional Deficits in Brain Volume in Schizophrenia: A Meta-Analysis of Voxel-Based Morphometry Studies
Authors: Robyn Honea, Tim J Crow, Dick Passingham, Clare E Mackay
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Voxel-based morphometry is a method for detecting group differences in the density or volume of brain matter. The authors reviewed the literature on use of voxel-based morphometry in schizophrenia imaging research to examine the capabilities of this method for clearly identifying specific structural differences in patients with schizophrenia, compared with healthy subjects. The authors looked for consistently reported results of relative deficits in gray and white matter in schizophrenia and evaluated voxel-based morphometry methods in order to propose a future strategy for using voxel-based morphometry in schizophrenia research. METHOD: The authors reviewed all voxel-based morphometry studies of schizophrenia that were published to May 2004 (15 studies). The studies included a total of 390 patients with a diagnosis of schizophrenia and 364 healthy volunteers. RESULTS: Gray and white matter deficits in patients with schizophrenia, relative to healthy comparison subjects, were reported in a total of 50 brain regions. Deficits were reported in two of the 50 regions in more than 50% of the studies and in nine of the 50 regions in one study only. The most consistent findings were of relative deficits in the left superior temporal gyrus and the left medial temporal lobe. Use of a smaller smoothing kernel (4–8 mm) led to detection of a greater number of regions implicated in schizophrenia. CONCLUSIONS: This review implicates the left superior temporal gyrus and the left medial temporal lobe as key regions of structural difference in patients with schizophrenia, compared to healthy subjects. The diversity of regions reported in voxel-based morphometry studies is in part related to the choice of variables in the automated process, such as smoothing kernel size and linear versus affine transformation, as well as to differences in patient groups. Voxel-based morphometry can be used as an exploratory whole-brain approach to identify abnormal brain regions in schizophrenia, which should then be validated by using region-of-interest analyses.
Impact of Taxon Sampling on the Estimation of Rates of Evolution at Sites
Authors: C. Blouin, D. Butt, A. J. Roger
Journal: Molecular Biology and Evolution (2004)

The function of individual sites within a protein influences their rate of accepted point mutation. During the computation of phylogenetic likelihoods, rate heterogeneity can be modeled on a site-per-site basis with relative rates drawn from a discretized Γ-distribution. Site-rate estimates (e.g., the rate of highest posterior probability given the data at a site) can then be used as a measure of evolutionary constraints imposed by function. However, if the sequence availability is limited, the estimation of rates is subject to sampling error. This article presents a simulation study that evaluates the robustness of evolutionary site-rate estimates for both small and phylogenetically unbalanced samples. The sampling error on rate estimates was first evaluated for alignments that included 5–45 sequences, sampled by jackknifing, from a master alignment containing 968 sequences. We observed that the potentially enhanced resolution among site rates due to the inclusion of a larger number of rate categories is negated by the difficulty in correctly estimating intermediate rates. This effect is marked for data sets with less than 30 sequences. Although the computation of likelihood theoretically accounts for phylogenetic distances through branch lengths, the introduction of a single long-branch outlier sequence had a significant negative effect on site-rate estimates. Finally, the presence of a shift in rates of evolution between related lineages can be diagnostic of a gain/loss of function within a protein family. Our analyses indicate that detecting these rate shifts is a harder problem than estimating rates. This is so, partially, because the difference in rates depends on two rate estimates, each with an intrinsic uncertainty. The performances of four methods to detect these site-rate shifts are evaluated and compared. Guidelines are suggested for preparing data sets minimally influenced by error introduced by sequence sampling.
Inhibitory capacity of alpha 1 antitrypsin in lung secretions: variability and the effect of drugs.
Authors: H M Morrison, S C Afford, R A Stockley
Journal: Thorax (1984)

The inhibitory function of alpha 1 antitrypsin (alpha 1AT) has been studied in the lung secretions of 31 patients with chronic obstructive bronchitis. The inhibitory capacity for a single sample showed a wide range (median 0.13 micrograms porcine pancreatic elastase (PPE) inhibited per microgram alpha 1 antitrypsin; range 0-0.55 micrograms), and all but five of 86 samples studied were capable of inhibiting some porcine pancreatic elastase. No sample showed free elastase activity, however. The inhibitory capacity, studied in six patients over five consecutive days, varied daily within the same individual (coefficient of variation 9.0-108.9%). Corticosteroid treatment (40 mg prednisone daily) increased the inhibitory capacity of sputum alpha 1 antitrypsin in 10 patients (2p less than 0.05) from a median value of 0.13 micrograms PPE inhibited per microgram alpha 1AT (range 0.06-0.36) before treatment to 0.22 micrograms PPE inhibited per microgram alpha 1AT (range 0.09-0.65) after treatment. The inhibitory capacity of sputum was higher than in the corresponding bronchoalveolar lavage sample from the same patient (2p less than 0.05; n = 10). The median value for sputum was 0.22 micrograms PPE inhibited per microgram alpha 1AT (range 0-0.55) and the value for lavage fluid was 0.07 micrograms PPE inhibited per microgram alpha 1AT (range 0-0.27).
Cognitive Neuropsychiatric Models of Persecutory Delusions
Authors: N J Blackwood, R J Howard, R P Bentall, R M Murray
Journal: American Journal of Psychiatry (2001)

The major cognitive theories of persecutory delusion formation and maintenance are critically examined in this article.The authors present a comprehensive review of the literature, citing results of relevant functional neuroimaging and neural network studies.People with persecutory delusions selectively attend to threatening information, jump to conclusions on the basis of insufficient information, attribute negative events to external personal causes, and have difficulty in envisaging others' intentions, motivations, or states of mind. Presence of the "reality distortion" cluster of psychotic symptoms correlates with cerebral blood flow in the left lateral prefrontal cortex, ventral striatum, superior temporal gyrus, and parahippocampal region. Social cognitive processing (selective attention to threat, attribution of causation or mental states) in normal subjects involves similar areas. Neural network models of persecutory delusions highlight the importance of disordered neuromodulation in their formation and of disordered neuroplasticity in their maintenance.Further studies examining the interaction of these cognitive processes, cross-sectionally and longitudinally, at cognitive psychological, neural network, and functional neuroanatomical levels are warranted to establish a comprehensive cognitive neuropsychiatric model of the persecutory delusion.
Lymphangiogenesis Correlates with Lymph Node Metastasis, Prognosis, and Angiogenic Phenotype in Human Non–Small Cell Lung Cancer
Authors: Ferenc Renyi-Vamos, Jozsef Tovari, Janos Fillinger, Jozsef Timar, Sandor Paku, Istvan Kenessey, Gyula Ostoros, Laszlo Agocs, Ibolya Soltesz, Balazs Dome
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recent experimental studies have revealed that lymphangiogenesis plays an important role in cancer progression, but its clinical significance in the case of non-small cell lung cancer (NSCLC) remains unclear. Our aim was to assess the lymphangiogenesis of human NSCLC, and to correlate this with angiogenic phenotype (angiogenic versus nonangiogenic growth pattern) and clinical behavior. Experimental Design: One hundred and three patients with NSCLC and complete follow-up information were included. Tumor samples were immunostained for vascular endothelial growth factor-C (VEGF-C), the lymphatic endothelial markers, LYVE-1 and D2-40/Podoplanin, and the panvascular marker, CD31. Lymphatic vessel density (LVD) and perimeters were evaluated within the tumor and peritumorally. Results: LVDs at the tumor periphery were significantly higher in lymph node metastatic tumors (P &amp;lt; 0.005) and high LVDs correlated with poor overall survival (P &amp;lt; 0.001). However, this tendency proved to be significant only in the angiogenic tumor group (P &amp;lt; 0.001). Although 68% of the patients with nonangiogenic tumors had lymph node metastasis (P = 0.0048 versus angiogenic tumors), in the patient group with nonangiogenic NSCLCs, there was no information from the LVDs in any investigated tumor area (P &amp;gt; 0.05). In contrast to angiogenic tumors, which had actively sprouting lymphatics in all of the investigated tumor areas, nonangiogenic tumors showed no Ki67 staining intratumorally. Conclusions: Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in NSCLC. Moreover, it also provides the first evidence that nonangiogenic NSCLCs mainly co-opt host tissue lymphatics during their growth, in contrast to most of the angiogenic tumors, which expand with concomitant lymphangiogenesis.
Unidirectional Evolutionary Transitions in Fungal Mating Systems and the Role of Transposable Elements
Authors: Anastasia Gioti, Alexandra A. Mushegian, Rebecka Strandberg, Jason E. Stajich, Hanna Johannesson
Journal: Molecular Biology and Evolution (2012)

In the fungal kingdom, the evolution of mating systems is highly dynamic, varying even among closely related species. Rearrangements in the mating-type (mat) locus, which contains the major regulators of sexual development, are expected to underlie the transitions between self-sterility (heterothallism) and self-fertility (homothallism). However, both the genetic mechanisms and the direction of evolutionary transitions in fungal mating systems are under debate. Here, we present new sequences of the mat locus of four homothallic and one heterothallic species of the model genus Neurospora (Ascomycota). By examining the patterns of synteny among these sequences and previously published data, we show that the locus is conserved among heterothallic species belonging to distinct phylogenetic clades, while different gene arrangements characterize the four homothallic species. These results allowed us to ascertain a heterothallic ancestor for the genus, confirming the prediction of the dead-end theory on unidirectional transitions toward selfing. We show that at least four shifts from heterothallism to homothallism have occurred in Neurospora, three of which involve the acquisition of sequences of both mating types into the same haploid genome. We present evidence for two genetic mechanisms allowing these shifts: translocation and unequal crossover. Finally, we identified two novel retrotransposons and suggest that these have played a major role in mating-system transitions, by facilitating multiple rearrangements of the mat locus.
In Utero Dietary Exposures and Risk of Islet Autoimmunity in Children
Authors: Carolyn M. Fronczak, Anna E. Barón, H. Peter Chase, Colleen Ross, Heather L. Brady, Michelle Hoffman, George S. Eisenbarth, Marian Rewers, Jill M. Norris
Journal: Diabetes Care (2003)

OBJECTIVE—The goal of this study was to examine whether maternal dietary intake of vitamin D, ω-3 fatty acids, and ω-6 fatty acids during pregnancy is associated with the appearance of islet autoimmunity (IA) in offspring. RESEARCH DESIGN AND METHODS—The Diabetes Autoimmunity Study in the Young (DAISY) is recruiting at birth and following children at increased risk for type 1 diabetes, as determined by HLA-DR genotype or by family history of type 1 diabetes. A total of 233 mothers of newly recruited DAISY subjects were asked to recall their intake of food and nutritional supplements during the third trimester of pregnancy using the Willett food frequency questionnaire. Children were followed for an average of 4 years (range 0.8–7.3 years) for the appearance of insulin, GAD65, and IA-2 autoantibodies. Sixteen children developed at least one autoantibody during this period. Unadjusted and adjusted hazard ratios (HRs) for the development of IA were estimated with survival analysis using a Weibull distribution. RESULTS—Maternal intake of vitamin D via food was significantly associated with a decreased risk of IA appearance in offspring, independent of HLA genotype, family history of type 1 diabetes, presence of gestational diabetes mellitus, and ethnicity (adjusted HR = 0.37; 95% CI 0.17–0.78). Vitamin D intake via supplements, ω-3 fatty acids, and ω-6 fatty acids intake during pregnancy were not associated with appearance of IA in offspring. CONCLUSIONS—Our findings suggest that maternal intake of vitamin D through food during pregnancy may have a protective effect on the appearance of IA in offspring.
Dynamic Interaction of &lt;sup&gt;111&lt;/sup&gt;Indium-Labeled Monoclonal Antibodies With Surface Antigens of Solid Tumors Visualized In Vivo by External Scintigraphy
Authors: K M Hwang, A M Keenan, J Frincke, G David, J Pearson, R K Oldham, A C Morgan
Journal: JNCI Journal of the National Cancer Institute (1986)

Two 111indium-labeled murine monoclonal antibodies (MoAb), D3 and 9.2.27, directed to tumor antigens of L-10 hepatocarcinoma and human melanoma, respectively, selectively localized antigen-positive target cells in guinea pigs and nude mice. The fate of MoAb differed in the two antigen-antibody systems after reacting with their corresponding tumor antigens in vivo as reflected by patterns of distribution and turnover in vivo. The 9.2.27 localized in melanoma xenograft in nude mice after intravenous administration with slow loss from tumor but more rapid loss from normal tissues and thus demonstrated optimal imaging of small tumors (approximately equal to 5 mm) between 3 and 6 days after injection of the radiolabeled antibody. In contrast, D3 demonstrated a biphasic localization in guinea pig L-10 hepatocarcinoma with a maximal activity on the 2d day after administration and showed rapid loss from both tumor and normal tissues. Nonspecific localization of antibodies in liver and in kidney was found both in syngeneic (nude mice) and xenogeneic (guinea pig) hosts but was more pronounced in the xenogeneic species. These results indicate that the nature of the antigen-antibody interaction may be of importance in selecting MoAb for both diagnosis and therapy of malignant diseases.
Angiotensin-converting enzyme inhibitor use and pneumonia risk in a general population
Authors: E. M. W. van de Garde
Journal: European Respiratory Journal (2006)

The aim of the present study was to assess whether the use of angiotensin-converting enzyme (ACE) inhibitors is associated with a decreased risk of hospitalisation for community-acquired pneumonia (CAP) in a general, essentially white population. Data were obtained from the Dutch PHARMO Record Linkage System. Cases were defined as patients with a first hospital admission for CAP. For each case, up to four population controls were matched by age and sex. The study population comprised 1,108 patients with a first hospital admission for CAP and 3,817 matched controls. After adjusting for several confounders, ACE inhibitor use was not associated with a decreased incidence of pneumonia (adjusted odds ratio (OR) 1.12; 95% confidence interval (CI) 0.88-1.43). Additionally, no significant association was observed in patients with diabetes, respiratory diseases, heart failure, or patients with both of the last two conditions. Furthermore, adjustment of treatment effects on pneumonia risk using stratification on balancing score also showed no significant association between ACE inhibitor use and pneumonia risk within the different strata (overall adjusted OR 1.09; 95% CI 0.87-1.36). In contrast with previous findings in Asian populations, the current authors were not able to confirm the beneficial effect of angiotensin-converting enzyme inhibitors on pneumonia risk in a general, essentially white population.
Return to sport after hip surgery for femoroacetabular impingement: a systematic review
Authors: Nicola C Casartelli, Michael Leunig, Nicola A Maffiuletti, Mario Bizzini
Journal: British Journal of Sports Medicine (2015)

We aimed to appraise (1) the rate of return to sport of athletes after hip surgery for femoroacetabular impingement (FAI) and (2) some aspects that may influence the return to sport.Four databases (EMBASE, PubMed, Web of Science, Cochrane Library) were searched until 21 October 2014. Studies evaluated return to sport of athletes who underwent hip surgery for the treatment of symptomatic FAI. A validated tool was used for quality evaluation of the studies.A total of 18 case series (level of evidence IV) with moderate-to-high methodological quality were included. On average, 87% of athletes returned to sport after hip surgery for FAI and 82% returned to the same sport level as before the occurrence of the symptoms. Professional athletes seem to return to sport at a higher rate compared with recreational and collegiate athletes. Sport participation after hip arthroscopy tends to decrease for professional athletes at short-term and mid-term follow-ups. Diffuse hip osteoarthritis at the time of surgery may not allow athletes to return to sport.Most athletes return to sport after hip surgery for the treatment of symptomatic FAI. The level of competition, time of evaluation after hip surgery and presence of articular cartilage lesions at the time of surgery may influence return to sport. Future studies with higher levels of evidence should describe and evaluate return to sport protocols after hip surgery for FAI.
Dietary Sugars Intake and Cardiovascular Health
Authors: Rachel K. Johnson, Lawrence J. Appel, Michael Brands, Barbara V. Howard, Michael Lefevre, Robert H. Lustig, Frank Sacks, Lyn M. Steffen, Judith Wylie-Rosett
Journal: Circulation (2009)

High intakes of dietary sugars in the setting of a worldwide pandemic of obesity and cardiovascular disease have heightened concerns about the adverse effects of excessive consumption of sugars. In 2001 to 2004, the usual intake of added sugars for Americans was 22.2 teaspoons per day (355 calories per day). Between 1970 and 2005, average annual availability of sugars/added sugars increased by 19%, which added 76 calories to Americans’ average daily energy intake. Soft drinks and other sugar-sweetened beverages are the primary source of added sugars in Americans’ diets. Excessive consumption of sugars has been linked with several metabolic abnormalities and adverse health conditions, as well as shortfalls of essential nutrients. Although trial data are limited, evidence from observational studies indicates that a higher intake of soft drinks is associated with greater energy intake, higher body weight, and lower intake of essential nutrients. National survey data also indicate that excessive consumption of added sugars is contributing to overconsumption of discretionary calories by Americans. On the basis of the 2005 US Dietary Guidelines, intake of added sugars greatly exceeds discretionary calorie allowances, regardless of energy needs. In view of these considerations, the American Heart Association recommends reductions in the intake of added sugars. A prudent upper limit of intake is half of the discretionary calorie allowance, which for most American women is no more than 100 calories per day and for most American men is no more than 150 calories per day from added sugars.
Survival outcome and cost-effectiveness with docetaxel and paclitaxel in patients with metastatic breast cancer: a population-based evaluation
Authors: T. Vu, S. Ellard, C.H. Speers, S.C.M. Taylor, M.L. de Lemos, F. Hu, K. Kuik, I.A. Olivotto
Journal: Annals of Oncology (2007)