tbuckley/cabot-search huggingface dataset:
Niflumic Acid Suppresses Interleukin-13–induced Asthma Phenotypes
Authors: Takako Nakano, Hiromasa Inoue, Satoru Fukuyama, Koichiro Matsumoto, Mikiko Matsumura, Miyuki Tsuda, Takafumi Matsumoto, Hisamichi Aizawa, Yoichi Nakanishi
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Chloride channels have been implicated in the regulation of mucus production in epithelial cells. Expression of hCLCA1, a calcium-activated chloride channel, has been reported to be increased in the airway epithelium of patients with asthma. Interleukin (IL)-13 induces the cardinal features of bronchial asthma, and glucocorticoids are not sufficient to suppress IL-13–induced airway hyperresponsiveness or goblet cell hyperplasia.Objectives: We studied the effects of chloride channel inhibitors in IL-13–induced asthma.Methods: The effects of niflumic acid (NA), a relatively specific blocker of calcium-activated chloride channel (CLCA), on goblet cell hyperplasia, eosinophil accumulation, and airway hyperresponsiveness were evaluated after IL-13 instillation into the airways. Because IL-13–dependent features rely on JAK/STAT6 signaling, the effect of NA on phosphorylation of JAK2 and STAT6 after IL-13 stimulation was examined in airway epithelial cells in vitro. The expression of the mCLCA family in mouse lung after IL-13 local administration in vivo was analyzed using reverse transcription–polymerase chain reaction.Measurements and Main Results: Treatment with NA inhibited not only IL-13–induced goblet cell hyperplasia but also airway hyperresponsiveness and eosinophilic infiltration. NA suppressed the eotaxin levels in bronchoalveolar lavage fluids and overexpression of the MUC5AC gene, a marker of goblet cell hyperplasia, in the lung after IL-13 instillation. NA suppressed JAK2 activation, STAT6 activation, and eotaxin expression in epithelial cells. The expression of mCLCA3 (mouse homolog hCLCA1), but not that of other CLCA family members, was up-regulated by IL-13.Conclusions: These findings suggest that a chloride channel inhibitor can control IL-13–mediated airway features at least by suppressing JAK/STAT6 activation.
Association Between Vaccination for Herpes Zoster and Risk of Herpes Zoster Infection Among Older Patients With Selected Immune-Mediated Diseases
Authors: Jie Zhang, Fenglong Xie, Elizabeth Delzell, Lang Chen, Kevin L. Winthrop, James D. Lewis, Kenneth G. Saag, John W. Baddley, Jeffrey R. Curtis
Journal: JAMA (2012)

ERPES ZOSTER (HZ), CAUSED by the reactivation of latent varicella-zoster virus (VZV), manifests as an acute, painful vesicular rash and is often accompanied by chronic pain or postherpetic neuralgia. 1In the United States, the incidence rate of HZ in the unvaccinated general population 50 years or older is estimated to be 7.0 cases per 1000 person-years. 2A live attenuated vaccine reduces HZ risk by 70% and 51% among immunocompetent individuals 50 to 59 years and 60 years and older in 2 randomized blinded trials, respectively. 3,4he Advisory Committee on Immunization Practices (ACIP) recommends a single dose of the zoster vaccine for all people 60 years or older. 5][10] Currently, the Food and Drug Administration (FDA), the ACIP, and the American College of Rheumatology consider the live HZ vaccine to be contraindicated in patients receiving some immunosuppressive medications commonly used to treat these conditions, including all immune-modulating biologic agents;
The Interactions Between Copper, Molybdenum, and Sulphur in Ruminant Nutrition
Authors: N F Suttle
Journal: Annual Review of Nutrition (1991)

INTRODUCTION .. . . . . . . . . . . . ...... . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . ........ . . . . . . . .. . . . . . . . . . . . 122 THIOMOLYBDATES: NUTRITIONAL DOUBTS AND CERTAINTIES ....   123 Qualitative Evidence for Thiomolybdate Formation in vivo . .. ..... . . . . . . . . . . . . .. . . . . . . . . 123 Qualitative Evidence for Thiomolybdate Inhibition of Copper Absorption ... . . . . . . . . . 123 Qualitative Evidence for Absorption of Thiomolybdates ......... . . . . . . . . . . . . . . . . . . . . . . . . . 124 Quantitative Evidence for Thiomolybdate Excretion in Feces...   . . . . . . . . . 124 Systemic Effects of Thiomolybdates   . . . . . . . . . . . . . . . . . . . . . . . . . 125 Conclusions on Physiological Importance of Thiomolybdates... .... . . . . . . . . . . . . . . . . . . . . . 129 NUTRITIONAL VARIABLES AFFECTING THE RUMEN INTERACTION . . ... . . . ... 130 Sulphur.......   . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 Molybdenum   131 Copper     . ...   131 Undigested Organic Matter   . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Sulphide-Trapping Agents .....   131 Copper-Trapping Agents  .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Post-RuminaIInteractions  132
Horizontal gene transfer from human endothelial cells to rat cardiomyocytes after intracoronary transplantation
Authors: Sandra Burghoff, Zhaoping Ding, Stefanie Gödecke, Alexander Assmann, Andreas Wirrwar, Doris Buchholz, Olga Sergeeva, Cordula Leurs, Helmut Hanenberg, Hans-Wilhelm Müller, Wilhelm Bloch, Jürgen Schrader
Journal: Cardiovascular Research (2007)

Recent studies suggested that human umbilical vein endothelial cells (HUVECs) transdifferentiate into cardiomyocytes and smooth muscle cells in vitro. To test the functional relevance of this observation, we examined the transdifferentiation potential of HUVECs in vivo after intracoronary cell application in Wistar rats. SPECT measurements (single photon emission computed tomography) revealed that 18% of 111In-labelled HUVECs infused by intracoronary delivery stably transplanted to the rat heart. For long-term tracking, HUVECs-expressing enhanced green fluorescent protein (EGFP) were infused. Two days following transplantation, HUVECs were positive for caspase-3. Within 3 days, EGFP was associated with individual cardiomyocytes. No labelling of endothelial and smooth muscle cells was observed. The total number of EGFP-labelled cardiomyocytes accounted for 58% of all initially trapped cells. These EGFP positive cells stained negatively for human mitochondrial proteins, but were positive for rat monocarboxylate transporter-1 protein (MCT-1). Furthermore, EGFP-mRNA was detected in these cells by single-cell RT–PCR (reverse transcription followed by polymerase chain reaction). After 21 days, EGFP positive cells were no longer observed. To investigate the underlying mechanism, we generated in vitro apoptotic bodies from EGFP-labelled HUVECs and found them to contain the genetic information for EGFP. Co-incubation of apoptotic bodies with neonatal rat cardiomyocytes caused cardiomyocytes to express EGFP. When transplanted into the rat heart by efficient intracoronary delivery, EGFP-expressing HUVECs cause the exclusive but transient labelling of cardiomyocytes. Our in vivo findings suggest that it is not cell fusion and/or transdifferentiation that occurs under these conditions but rather a horizontal gene transfer of the EGFP marker via apoptotic bodies from endothelial cells to cardiomyocytes.
Clinicopathologic and Prognostic Significance of an Angiogenic Factor, Thymidine Phosphorylase, in Human Colorectal Carcinoma
Authors: Y. Takebayashi, S.-i. Akiyama, S. Akiba, K. Yamada, K. Miyadera, T. Sumizawa, Y. Yamada, F. Murata, T. Aikou
Journal: JNCI Journal of the National Cancer Institute (1996)

Platelet-derived endothelial cell growth factor (PD-ECGF) is known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We previously found that thymidine phosphorylase (dThdPase) and PD-ECGF are the same protein.We retrospectively examined the expression of dThdPase in primary colorectal carcinomas, its association with angiogenesis and clinicopathologic findings, and its prognostic value.Tissues were obtained from the tumors of 163 patients whose colorectal carcinomas were completely removed by surgery. Microvessels assessed by immunostaining endothelial cells for factor VIII were counted on a 400x field in the most active areas of neovascularization within the tumor. We purified the monoclonal antibody against dThdPase and studied the expression of dThdPase in the same serial sections used for the detection of factor VIII. Those who carried out microvessel counting and dThdPase expression assessment had no knowledge of clinicopathologic findings. The significance of dThdPase in the prognosis of patients with colorectal carcinomas was also examined in the survival analysis of mortality follow-up data covering the period between 1984 through 1991. Reported P values are from two-sided tests of statistical significance.The mean microvessel count (+/- standard deviation) in dThdPase-positive colorectal carcinoma specimens (17.5 +/- 7.2) was higher (P < .001) than that in dThdPase-negative carcinoma specimens (9.3 +/- 5.5). The dThdPase positivity was in accordance with the microvessel count. dThdPase positivity showed highly significant statistical associations with tumor size, extent of invasion, lymph node metastasis, lymphatic invasion, and venous invasion. Cox regression analysis revealed that dThdPase expression was prognostic for poor disease outcome after adjustment for Dukes' stage and microvessel count.These findings suggest that higher levels of dThdPase expression in colorectal carcinomas are associated with more extensive angiogenesis, poor clinical and laboratory findings, and unfavorable clinical outcome.Inhibition of dThdPase in human colorectal carcinomas might improve prognosis for some patients.
Progesterone/RANKL Is a Major Regulatory Axis in the Human Breast
Authors: Tamara Tanos, George Sflomos, Pablo C. Echeverria, Ayyakkannu Ayyanan, Maria Gutierrez, Jean-Francois Delaloye, Wassim Raffoul, Maryse Fiche, William Dougall, Pascal Schneider, Ozden Yalcin-Ozuysal, Cathrin Brisken
Journal: Science Translational Medicine (2013)

Ex vivo model identifies the progesterone/RANKL axis as an important proliferative stimulus in the human breast.
Mobilization of Endothelial Progenitor Cells in Patients With Acute Myocardial Infarction
Authors: Satoshi Shintani, Toyoaki Murohara, Hisao Ikeda, Takafumi Ueno, Tomoki Honma, Atsushi Katoh, Ken-ichiro Sasaki, Toshifumi Shimada, Yuichi Oike, Tsutomu Imaizumi
Journal: Circulation (2001)

Background —Endothelial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNC CD34+ ), are mobilized into PB in acute ischemic events in humans. Methods and Results —Flow cytometry revealed that circulating MNC CD34+ counts significantly increased in patients with acute myocardial infarction (n=16), peaking on day 7 after onset, whereas they were unchanged in control subjects (n=8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively correlated with circulating MNC CD34+ counts ( r =0.35, P =0.01). Conclusions —This is the first clinical demonstration showing that lineage-committed EPCs and MNC CD34+ , their putative precursors, are mobilized during an acute ischemic event in humans.
Microscopic pulmonary embolisation of an indwelling central venous catheter with granulomatous inflammatory response
Authors: A. Baydur, M. N. Koss, O. P. Sharma, G. E. Dalgleish, D. V. Nguyen, F. G. Mullick, L. A. Murakata, J. A. Centeno
Journal: European Respiratory Journal (2005)

Indwelling catheters can disintegrate into tiny fragments and embolise. Once the fragments are detected radiographically, they can be removed using vascular intervention techniques. Rarely, indwelling catheters dwindle into inextricable pieces that embolise into minute pulmonary vessels and lymphatics, causing granulomatous changes microscopically. The present study reports a 54-yr-old female who had received several indwelling central lines during several abdominal surgeries over a 5-yr period. The patient developed a noncaseating granulomatous skin lesion followed by exertional dyspnoea a few months later. Chest radiographs and computed tomography showed diffuse interstitial infiltrates. Open lung biopsy showed two types of granulomas: 1) peri-lymphangitic and peri-bronchiolar non-necrotising granulomas consistent with sarcoidosis; and 2) distinct foreign body granulomas. In some of the foreign body granulomas, confocal Raman spectroscopy identified the presence of bisphenol-A-polycarbonate, a polymer commonly used in biomedical devices. The patient improved following treatment with prednisone followed by methotrexate. The present case illustrates an interesting combination of two causes of granulomatous disease, the importance of examining all biopsy specimens from sarcoidosis patients for foreign particles and the rare occurrence of microscopic embolisation of catheter fragments to the lung with foreign-body giant cell reaction to them.
Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer
Authors: Troels Schepeler, Jørgen T. Reinert, Marie S. Ostenfeld, Lise L. Christensen, Asli N. Silahtaroglu, Lars Dyrskjøt, Carsten Wiuf, Frank J. Sørensen, Mogens Kruhøffer, Søren Laurberg, Sakari Kauppinen, Torben F. Ørntoft, Claus L. Andersen
Journal: Cancer Research (2008)

MicroRNAs (miRNA) are a class of small noncoding RNAs with important posttranscriptional regulatory functions. Recent data suggest that miRNAs are aberrantly expressed in many human cancers and that they may play significant roles in carcinogenesis. Here, we used microarrays to profile the expression of 315 human miRNAs in 10 normal mucosa samples and 49 stage II colon cancers differing with regard to microsatellite status and recurrence of disease. Several miRNAs were differentially expressed between normal tissue and tumor microsatellite subtypes, with miR-145 showing the lowest expression in cancer relative to normal tissue. Microsatellite status for the majority of cancers could be correctly predicted based on miRNA expression profiles. Furthermore, a biomarker based on miRNA expression profiles could predict recurrence of disease with an overall performance accuracy of 81%, indicating a potential role of miRNAs in determining tumor aggressiveness. The expression levels of miR-320 and miR-498, both included in the predictive biomarker, correlated with the probability of recurrence-free survival by multivariate analysis. We successfully verified the expression of selected miRNAs using real-time reverse transcription-PCR assays for mature miRNAs, whereas in situ hybridization was used to detect the accumulation of miR-145 and miR-320 in normal epithelial cells and adenocarcinoma cells. Functional studies showed that miR-145 potently suppressed growth of three different colon carcinoma cell lines. In conclusion, our results suggest that perturbed expression of numerous miRNAs in colon cancer may have a functional effect on tumor cell behavior, and, furthermore, that some miRNAs with prognostic potential could be of clinical importance.
Adult liver transplantation: An analysis of the early causes of death in 40 consecutive cases
Authors: Valentin Cuervas-Mons, Julio A. Martinez, Andrew Dekker, Thomas E. Starzl, David H. Van Thiel
Journal: Hepatology (1986)

One hundred twenty-nine adult patients who received an orthotopic liver transplantation and survived at least 24 hr after surgery were evaluated. During the period of follow-up, 48 of the 129 patients (37%) died. Only 40 of these 48 patients died at our institution and were included in this study. Seventeen of the 40 deaths (42.5%) occurred during the first month after orthotopic liver transplantation and 30 of the 40 deaths (75%) occurred during the first 60 days post-orthotopic liver transplantation. Death was related to infection in 21 cases (52.5%), to multiorgan failure in 8 (20%) and to uncontrollable rejection in 3 (7.6%). The remaining eight deaths (20%) were attributed to a variety of other causes. Eleven of the 21 deaths related to infection (52%) occurred during the first month after orthotopic liver transplantation. Bacterial sepsis was the leading cause of death and accounted for 17 of the 21 deaths (81%) in which infection was present at the time of death. The most frequently isolated bacteria were Pseudomonas and other enteric Gram-negative bacilli. Three patients had complete occlusion of the hepatic artery of the grafted liver. Six patients developed massive infarction of the liver despite patent vascular anastomoses. Histological signs of rejection were seen in 9 of the 31 patients autopsied (29%), but in only 3 of these (9.6%) was rejection the principal cause of death. The biliary anastomoses were patent in all 31 cases examined at autopsy.
In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas
Authors: K. Lacrima, A. Valentini, C. Lambertini, M. Taborelli, A. Rinaldi, E. Zucca, C. Catapano, F. Cavalli, A. Gianella-Borradori, D.E. MacCallum, F. Bertoni
Journal: Annals of Oncology (2005)
The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment
Authors: Xuan Zhang, Dongya Zhang, Huijue Jia, Qiang Feng, Donghui Wang, Di Liang, Xiangni Wu, Junhua Li, Longqing Tang, Yin Li, Zhou Lan, Bing Chen, Yanli Li, Huanzi Zhong, Hailiang Xie, Zhuye Jie, Weineng Chen, Shanmei Tang, Xiaoqiang Xu, Xiaokai Wang, Xianghang Cai, Sheng Liu, Yan Xia, Jiyang Li, Xingye Qiao, Jumana Yousuf Al-Aama, Hua Chen, Li Wang, Qing-jun Wu, Fengchun Zhang, Wenjie Zheng, Yongzhe Li, Mingrong Zhang, Guangwen Luo, Wenbin Xue, Liang Xiao, Jun Li, Wanting Chen, Xun Xu, Ye Yin, Huanming Yang, Jian Wang, Karsten Kristiansen, Liang Liu, Ting Li, Qingchun Huang, Yingrui Li, Jun Wang
Journal: Nature Medicine (2015)
Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment
Authors: Kavitha Gopal, Timothy C. Johnson, Saraswathi Gopal, Aaron Walfish, Christine T. Bang, Pauline Suwandhi, Helene N. Pena-Sahdala, David J. Clain, Henry C. Bodenheimer, Albert D. Min
Journal: Hepatology (2006)

The low-density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for the hepatitis C virus (HCV). Competitive inhibition of HCV binding to the LDLR by low-density lipoprotein (LDL) has been shown in vitro. If similar inhibition occurs in vivo, an elevated serum concentration of beta-lipoproteins may reduce the efficiency of infecting hepatocytes with HCV by competitively inhibiting HCV viral receptor binding. We investigated the role of baseline lipid values in influencing the outcome of HCV treatment. We conducted a retrospective chart review of patients treated with an interferon-based regimen at our liver and gastroenterology clinics between 1998 and 2004. Of 99 patients enrolled in the study, 49 (49.5%) had HCV genotype 1 (LDL 100.2 +/- 30.2 mg/dL [mean +/- SD]), and 50 patients (50.5%) had genotype 2 or 3 (LDL 110.1 +/- 40 mg/dL) infection. Early viral response (EVR), end-of-treatment response (ETR), and sustained viral response (SVR) were documented in 99, 88, and 77 patients, respectively. LDL and cholesterol levels prior to treatment were found to be higher in patients with positive EVR, ETR, and SVR. This difference remained significant independent of age. Multivariate analysis controlling for genotype and age showed that the higher the cholesterol and LDL levels prior to treatment, the greater the odds of responding to treatment. In conclusion, having higher serum LDL and cholesterol levels before treatment may be significant prognostic indicators for treatment outcome of those with chronic hepatitis C infection, particularly in genotypes 1 and 2.
Oxford case histories in gastroenterology and hepatology
Authors: James O Lindsay
Journal: Gut (2010)

Edited by AJ Walsh, OC Buchel, J Collier , SPL Travis. Published by Oxford University Press, Oxford UK, 2010, pp 353, £39.95 (softback). ISBN 978-0-19-955789-9 

Over the last few years I have begun to question the purpose of traditional medical text books. Specialist texts covering defined clinical or research areas rapidly become outdated due to the pace of ongoing clinical and basic science research. Classic student/training textbooks are being replaced by alternative formats such as web-based interactive learning, CD-ROMs and dedicated updated websites. Certainly, when I want to find out up-to-date information I rarely reach for the thick tomes gathering dust on the top shelf, and am much more likely to exercise …
Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells.
Authors: J W Heinecke, L Baker, H Rosen, A Chait
Journal: Journal of Clinical Investigation (1986)

Extracellular superoxide was detected in cultures of monkey and human arterial smooth muscle cells as indicated by superoxide dismutase inhibitable reduction of cytochrome c. Superoxide production by these cells in the presence of Fe or Cu resulted in modification of low density lipoprotein (LDL). The degree of LDL modification was directly proportional to the rate of superoxide production by cells. Superoxide dismutase (100 micrograms/ml), and the general free radical scavengers butylated hydroxytoluene and butylated hydroxyanisole (50 microM), inhibited Fe- and Cu-mediated modification of LDL by monkey smooth muscle cells, while catalase (100 micrograms/ml) and mannitol (25 mM) had no effect. The chelators desferrioxamine and diethylenetriamine pentaacetic acid completely inhibited Fe- and Cu-promoted modification of LDL, while EGTA had no inhibitory effect. EDTA stimulated Fe-promoted modification in the 1-100 microM range while inhibiting Cu-mediated modification of LDL. LDL modified by smooth muscle cells in the presence of 10 microM Fe or Cu stimulated [14C]oleate incorporation into cholesteryl ester by human macrophages and murine J774 cells to a degree comparable to that produced by acetylated LDL. LDL incubated with smooth muscle cells and metal ions in the presence of superoxide dismutase failed to enhance macrophage cholesteryl ester accumulation. Thus, arterial smooth muscle cells in culture generate superoxide and modify LDL by a superoxide-dependent, Fe or Cu catalyzed free radical process, resulting in enhanced uptake of the modified LDL by macrophages. Neither hydroxyl radicals nor H2O2 are likely to be involved. Superoxide-dependent lipid peroxidation may contribute to biological modification of LDL, resulting in foam cell formation and atherogenesis.