tbuckley/cabot-search huggingface dataset:
Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System
Authors: Gabriele Niedermann, Rudolf Grimm, Elke Geier, Martina Maurer, Claudio Realini, Christoph Gartmann, Jürgen Soll, Satoshi Omura, Martin C. Rechsteiner, Wolfgang Baumeister, Klaus Eichmann
Journal: The Journal of Experimental Medicine (1997)

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH2 and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon γ induction in vivo or addition of recombinant proteasome activator 28α in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules.
EphB/EphrinB Receptors and Wnt Signaling in Colorectal Cancer
Authors: Hans Clevers, Eduard Batlle
Journal: Cancer Research (2006)

Eph receptors and their ephrin ligands mediate cell repulsion during embryonic development. In the intestinal epithelium, EphB receptors are Wnt signaling target genes that control cell compartmentalization along the crypt axis. Recent findings have shown that this family of receptors are key players during colorectal cancer progression. Here, we review the current knowledge of the EphB/ephrinB system in the intestinal epithelium and we discuss their tumor suppressor role in the context of the multistep progression of colorectal cancer.
Detection of the action of salicylic acid on the normal stratum corneum
Authors: D. L. ROBERTS, R. MARSHALL, R. MARKS
Journal: British Journal of Dermatology (1980)

The undoubted clinical usefulness of salicylic acid contrasts markedly with its barely detectable action on normal skin. In this study we have attempted to extend our understanding of the action of salicylic acid by monitoring its effect on the stratum corneum using newly developed techniques for assessing desquamation, as well as using conventional methods for measuring other aspects of epidermal activity. Our findings have succeeded in demonstrating that salicylic acid enhances the shedding of corneocytes and we suggest that this compound in some way decreases corneocyte to corneocyte cohesion. We have confirmed that salicylic acid has no effect on the mitotic activity of the normal epidermis.
Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism
Authors: Paul D. Stein
Journal: Annals of Internal Medicine (2010)

Background: The accuracy of gadolinium-enhanced magnetic resonance pulmonary angiography and magnetic resonance venography for diagnosing pulmonary embolism has not been determined conclusively. Objective: To investigate performance characteristics of magnetic resonance angiography, with or without magnetic resonance venography, for diagnosing pulmonary embolism. Design: Prospective, multicenter study from 10 April 2006 to 30 September 2008. (ClinicalTrials.gov registration number: NCT00241826) Setting: 7 hospitals and their emergency services. Patients: 371 adults with diagnosed or excluded pulmonary embolism. Measurements: Sensitivity, specificity, and likelihood ratios were measured by comparing independently read magnetic resonance imaging with the reference standard for diagnosing pulmonary embolism. Reference standard diagnosis or exclusion was made by using various tests, including computed tomographic angiography and venography, ventilation–perfusion lung scan, venous ultrasonography, d-dimer assay, and clinical assessment. Results: Magnetic resonance angiography, averaged across centers, was technically inadequate in 25% of patients (92 of 371). The proportion of technically inadequate images ranged from 11% to 52% at various centers. Including patients with technically inadequate images, magnetic resonance angiography identified 57% (59 of 104) with pulmonary embolism. Technically adequate magnetic resonance angiography had a sensitivity of 78% and a specificity of 99%. Technically adequate magnetic resonance angiography and venography had a sensitivity of 92% and a specificity of 96%, but 52% of patients (194 of 370) had technically inadequate results. Limitation: A high proportion of patients with suspected embolism was not eligible or declined to participate. Conclusion: Magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. Magnetic resonance pulmonary angiography and magnetic resonance venography combined have a higher sensitivity than magnetic resonance pulmonary angiography alone in patients with technically adequate images, but it is more difficult to obtain technically adequate images with the 2 procedures. Primary Funding Source: National Heart, Lung, and Blood Institute.
Treatment Outcomes and Long-term Survival in Patients with Extensively Drug-resistant Tuberculosis
Authors: Doh Hyung Kim, Hee Jin Kim, Seung-Kyu Park, Suck-Jun Kong, Young Sam Kim, Tae-Hyung Kim, Eun Kyung Kim, Ki Man Lee, Sung Soon Lee, Jae Seuk Park, Won-Jung Koh, Chang-Hoon Lee, Ji Yeon Kim, Tae Sun Shim
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The increasing worldwide incidence of extensively drug-resistant tuberculosis (XDR-TB) has emerged as a threat to public health and tuberculosis (TB) control. Treatment outcomes have varied among studies, and data on long-term survival are still scarce.To retrospectively assess the burden, clinical characteristics, treatment outcomes, and long-term survival rate of patients with XDR-TB in a cohort of patients with HIV-negative multidrug-resistant tuberculosis (MDR-TB) in South Korea.Medical records were reviewed of patients newly diagnosed with or retreated for MDR-TB from 2000 to 2002. The cohort was monitored for 3 to 7 years after the initiation of treatment. Initial treatment outcomes and cumulative survival rates were analyzed, and predictors of treatment success and survival were defined.Of 1,407 patients with MDR-TB 75 (5.3%) had XDR-TB at treatment initiation. The default rate was high (453/1,407; 32%), and patients with XDR-TB had lower treatment success (29.3 vs. 46.2%; P = 0.004) and higher all-cause (49.3 vs. 19.4%; P < 0.001) and TB-related disease mortality (41.3 vs. 11.8%; P < 0.001) than other patients with MDR-TB. The presence of XDR-TB significantly affected treatment success (odds ratio, 0.23; 95% confidence interval [CI], 0.08-0.64; P = 0.005), all-cause mortality (hazards ratio, 3.25; 95% CI, 1.91-5.53; P < 0.001), and TB-related mortality (hazards ratio, 4.45; 95% CI, 2.48-8.00; P < 0.001) on multivariate analyses.XDR-TB occurred in a substantial proportion of patients with MDR-TB in South Korea, and was the strongest predictor of treatment outcomes and long-term survival in patients with MDR-TB. Adequate TB control policies should be implemented to prevent the further development and spread of drug resistance.
A Novel IκB Kinase-β Inhibitor Ameliorates Bleomycin-induced Pulmonary Fibrosis in Mice
Authors: Mami Inayama, Yasuhiko Nishioka, Momoyo Azuma, Susumu Muto, Yoshinori Aono, Hideki Makino, Kenji Tani, Hisanori Uehara, Keisuke Izumi, Akiko Itai, Saburo Sone
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

IkappaB kinase-beta is a critical regulator in the activation of nuclear factor-kappaB (NF-kappaB), a transcription factor related to the expression and regulation of proinflammatory cytokines.To evaluate if inhibition of IkappaB kinase-beta ameliorates pneumonitis and pulmonary fibrosis.We examined whether a novel IkappaB kinase-beta inhibitor, IMD-0354, attenuates bleomycin-induced pulmonary fibrosis in mice.Administration of IMD-0354 significantly improved the loss of body weight and survival of mice treated with bleomycin, whereas IMD-0354 alone did not cause any morphologic change in the lung. When mice were evaluated 28 d after bleomycin administration, IMD-0354 dose-dependently reduced the collagen content and fibrotic scores as shown by histologic examination. The findings in the bronchoalveolar lavage demonstrated that the proportions of neutrophils and lymphocytes were decreased in mice treated with IMD-0354 on Day 7 and 14, respectively. IMD-0354 treatment was confirmed to inhibit the activation of NF-kappaB, but not activator protein-1, in the lungs treated with bleomycin. The production of inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta was reduced in the lungs of mice treated with IMD-0354.These results suggest that IMD-0354 might be useful to ameliorate the inflammation in the lungs induced by fibrotic injury and the subsequent fibrogenesis via inhibiting the expression of profibrotic cytokines related to the activation of NF-kappaB.
Rod-type cyclic nucleotide-gated cation channel is expressed in vascular endothelium and vascular smooth muscle cells
Authors: X Yao
Journal: Cardiovascular Research (1999)

Objectives: Ca++-permeable nonselective cation channels mediate the entry of extracellular Ca++ in vascular endothelium. They are also partly responsible for Ca++ entry in vascular smooth muscle cells (SMCs). The molecular identities of these channels have not been identified. The aim of this study is to examine whether rod-type nucleotide-gated nonselective cation (CNG1) channel, a channel which has been molecularly cloned, is related to the nonselective channels in vascular cells. Methods: We used RT-PCR, molecular cloning, northern Blot and in situ hybridization to examine the expression of CNG1 mRNA in a variety of guinea pig and rat blood vessels with different diameters and in cultured vascular endothelial cells and vascular smooth muscle cells. Results: We have cloned a 402-bp partial cDNA of CNG1 channel from guinea pig mesenteric arteries. RT-PCR and southern blot results indicate that the CNG1 mRNA is expressed in both cultured vascular endothelial and cultured vascular SMCs. Northern blot revealed the transcripts of ∼3.2 kb, ∼5.0 kb, and ∼1.8 kb in cultured endothelial cells. In situ hybridization yielded strong labeling in endothelium layer of aorta, medium-sized mesenteric arteries, and small mesenteric arteries. Conclusion: Our findings suggest a potential role of CNG protein for Ca++ entry in vascular endothelium and vascular smooth muscles. The high expression of CNG1 mRNA in the endothelium of medium-sized arteries and small-sized arteries implicates a possible involvement of CNG1 protein in the regulation of blood supply to different regions and in the regulation of arterial blood pressure.
Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging
Authors: M.E. Kooi, V.C. Cappendijk, K.B.J.M. Cleutjens, A.G.H. Kessels, P.J.E.H.M. Kitslaar, M. Borgers, P.M. Frederik, M.J.A.P. Daemen, J.M.A. van Engelshoven
Journal: Circulation (2003)

One of the features of high-risk atherosclerotic plaques is a preponderance of macrophages. Experimental studies with hyperlipidemic rabbits have shown that ultrasmall superparamagnetic particles of iron oxide (USPIOs) accumulate in plaques with a high macrophage content and that this induces magnetic resonance (MR) signal changes. The purpose of our study was to investigate whether USPIO-enhanced MRI can also be used for in vivo detection of macrophages in human plaques.MRI was performed on 11 symptomatic patients scheduled for carotid endarterectomy before and 24 (n=11) and 72 (n=5) hours after administration of USPIOs (Sinerem) at a dose of 2.6 mg Fe/kg. Histological and electron microscopical analyses of the plaques showed USPIOs primarily in macrophages within the plaques in 10 of 11 patients. Histological analysis showed USPIOs in 27 of 36 (75%) of the ruptured and rupture-prone lesions and 1 of 14 (7%) of the stable lesions. Of the patients with USPIO uptake, signal changes in the post-USPIO MRI were observed by 2 observers in the vessel wall in 67 of 123 (54%) and 19 of 55 (35%) quadrants of the T2*-weighted MR images acquired after 24 and 72 hours, respectively. For those quadrants with changes, there was a significant signal decrease of 24% (95% CI, 33% to 15%) in regions of interest in the images acquired after 24 hours, whereas no significant signal change was found after 72 hours.Accumulation of USPIOs in macrophages in predominantly ruptured and rupture-prone human atherosclerotic lesions caused signal decreases in the in vivo MR images.
Method of detection is a prognostic factor for outcome among women diagnosed with early stage breast cancer.
Authors: AM Brewster, PA Thompson, Y Cao, JL Murray, MM Stewart, DA Berry, ML Bondy
Journal: Cancer Research (2009)

Abstract Abstract #5005 Background: The reduction in breast cancer mortality over the past several decades has been partially attributed to the impact of screening mammograms. Breast cancers detected by screening mammograms tend to be at an earlier stage than those detected as a result of symptoms. The magnitude of the impact of method of detection on breast cancer survival beyond this phenomenon, known as stage shift, is not well defined. We therefore evaluated the independent prognostic effect of method of detection among women diagnosed in early stages of disease (stage I and II breast cancers). Methods: Medical records from 2,143 women aged 40 or older with stage I and II breast cancers, treated at the M.D. Anderson Cancer Center between 1985 and 2000 were used to derive information on method of breast cancer detection, clinical and histological tumor characteristics. Cox proportional hazards models were used to estimate the hazard ratios (HR) of breast cancer recurrence and breast cancer-specific death adjusted for age at diagnosis, year of diagnosis, nuclear grade, hormone receptor status, systemic treatment and stage at diagnosis. All statistical tests were two-sided. Results: Patients ages 40-49, 50-69 and ≥70 with symptom compared to screen-detected breast cancers were statistically significantly more likely to be diagnosed with stage II versus stage I disease and were more likely to have higher nuclear grade III versus grade I tumors. Symptom-detected breast cancers were associated with an increased risk of breast cancer recurrence (HR 1.9, 95% confidence interval (CI) 1.4-2.6) and breast cancer-specific death (HR 2.0, 95% CI 1.4-3.0) than screen-detected breast cancers after adjusting for age at diagnosis, year of diagnosis, tumor size, lymph node involvement, tumor characteristics and systemic treatment. Discussion: Our data from a large cohort of breast cancer patients with long-term follow-up indicate that even among patients with early stage disease; those with symptom-detected breast cancers have a worse prognosis. Consideration should be given to including method of detection as a prognostic factor when making treatment decisions for patients with stage I and II breast cancers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5005.
Response to Letter Regarding Article, “High-Density Lipoproteins and Their Constituent, Sphingosine-1-Phosphate, Directly Protect the Heart Against Ischemia/Reperfusion Injury In Vivo via the S1P <sub>3</sub> Lysophospholipid Receptor”
Authors: Gregor Theilmeier, Christoph Schmidt, Jörg Herrmann, Petra Keul, Michael Schäfers, Ilka Herrgott, Jan Mersmann, Jan Larmann, Sven Hermann, Jörg Stypmann, Otmar Schober, Reinhard Hildebrand, Reiner Schulz, Gerd Heusch, Michael Haude, Karin von Wnuck Lipinski, Christine Herzog, Martina Schmitz, Raimund Erbel, Jerold Chun, Bodo Levkau
Journal: Circulation (2007)
Air Pollution from Traffic and the Development of Respiratory Infections and Asthmatic and Allergic Symptoms in Children
Authors: Michael Brauer, Gerard Hoek, Patricia Van Vliet, Kees Meliefste, Paul H. Fischer, Alet Wijga, Laurens P. Koopman, Herman J. Neijens, Jorrit Gerritsen, Marjan Kerkhof, Joachim Heinrich, Tom Bellander, Bert Brunekreef
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Despite the important contribution of traffic sources to urban air quality, relatively few studies have evaluated the effects of traffic-related air pollution on health, such as its influence on the development of asthma and other childhood respiratory diseases. We examined the relationship between traffic-related air pollution and the development of asthmatic/allergic symptoms and respiratory infections in a birth cohort (n ∼ 4,000) study in The Netherlands. A validated model was used to assign outdoor concentrations of traffic-related air pollutants (nitrogen dioxide, particulate matter less than 2.5 μm in aerodynamic diameter, and “soot”) at the home of each subject of the cohort. Questionnaire-derived data on wheezing, dry nighttime cough, ear, nose, and throat infections, skin rash, and physician-diagnosed asthma, bronchitis, influenza, and eczema at 2 years of age were analyzed in relation to air pollutants. Adjusted odds ratios for wheezing, physician-diagnosed asthma, ear/nose/throat infections, and flu/serious colds indicated positive associations with air pollutants, some of which reached borderline statistical significance. No associations were observed for the other health outcomes analyzed. Sensitivity analyses generally supported these results and suggested somewhat stronger associations with traffic, for asthma that was diagnosed before 1 year of age. These findings are subject to confirmation at older ages, when asthma can be more readily diagnosed.
HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer
Authors: Andrew E. Teschendorff, Shih-Han Lee, Allison Jones, Heidi Fiegl, Marie Kalwa, Wolfgang Wagner, Kantaraja Chindera, Iona Evans, Louis Dubeau, Arturo Orjalo, Hugo M. Horlings, Lukas Niederreiter, Arthur Kaser, Winnie Yang, Ellen L. Goode, Brooke L. Fridley, Richard G. Jenner, Els M.J.J. Berns, Elisabeth Wik, Helga B. Salvesen, G. Bea A. Wisman, Ate G.J. van der Zee, Ben Davidson, Claes G. Trope, Sandrina Lambrechts, Ignace Vergote, Hilary Calvert, Ian J. Jacobs, Martin Widschwendter
Journal: Genome Medicine (2015)

Understanding carboplatin resistance in ovarian cancer is critical for the improvement of patients' lives. Multipotent mesenchymal stem cells or an aggravated epithelial to mesenchymal transition phenotype of a cancer are integrally involved in pathways conferring chemo-resistance. Long non-coding RNA HOTAIR (HOX transcript antisense intergenic RNA) is involved in mesenchymal stem cell fate and cancer biology. We analyzed HOTAIR expression and associated surrogate DNA methylation (DNAme) in 134 primary ovarian cancer cases (63 received carboplatin, 55 received cisplatin and 16 no chemotherapy). We validated our findings by HOTAIR expression and DNAme analysis in a multicentre setting of five additional sets, encompassing 946 ovarian cancers. Chemo-sensitivity has been assessed in cell culture experiments. HOTAIR expression was significantly associated with poor survival in carboplatin-treated patients with adjusted hazard ratios for death of 3.64 (95 % confidence interval [CI] 1.78–7.42; P < 0.001) in the discovery and 1.63 (95 % CI 1.04–2.56; P = 0.032) in the validation set. This effect was not seen in patients who did not receive carboplatin (0.97 [95 % CI 0.52–1.80; P = 0.932]). HOTAIR expression or its surrogate DNAme signature predicted poor outcome in all additional sets of carboplatin-treated ovarian cancer patients while HOTAIR expressors responded preferentially to cisplatin (multivariate interaction P = 0.008). Non-coding RNA HOTAIR or its more stable DNAme surrogate may indicate the presence of a subset of cells which confer resistance to carboplatin and can serve as (1) a marker to personalise treatment and (2) a novel target to overcome carboplatin resistance.
Tetrameric Complexes of Human Histocompatibility Leukocyte Antigen (HLA)-G Bind to Peripheral Blood Myelomonocytic Cells
Authors: David S.J. Allan, Marco Colonna, Lewis L. Lanier, Tatyana D. Churakova, John S. Abrams, Shirley A. Ellis, Andrew J. McMichael, Veronique M. Braud
Journal: The Journal of Experimental Medicine (1999)

The nonclassical MHC class I molecule human histocompatibility leukocyte antigen (HLA)-G is selectively expressed on fetal trophoblast tissue at the maternal–fetal interface in pregnancy. It has long been suggested that HLA-G may inhibit maternal natural killer (NK) cells through interaction with particular NK cell receptors (KIRs). To investigate interactions of HLA-G, we constructed phycoerythrin-labeled tetrameric complexes of HLA-G refolded with a self-peptide. These HLA-G tetramers failed to bind to NK cells and cells transfected with CD94/NKG2 and killer immunoglobulin-like NK receptors. In contrast, HLA-G tetramers did bind to peripheral blood monocytes, staining a CD16+CD14mid subset with greater intensity. On transfectants, HLA-G tetramers bound to inhibitory immunoglobulin-like transcript (ILT)2 and ILT4 receptors. However, staining in the presence of antibodies reactive with ILT receptors revealed that the interaction of HLA-G tetramers with blood monocytes was largely due to binding to ILT4. These results suggest that the primary role of HLA-G may be the modulation of myelomonocytic cell behavior in pregnancy.
Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease
Authors: Marta Martinez-Vicente, Zsolt Talloczy, Esther Wong, Guomei Tang, Hiroshi Koga, Susmita Kaushik, Rosa de Vries, Esperanza Arias, Spike Harris, David Sulzer, Ana Maria Cuervo
Journal: Nature Neuroscience (2010)