tbuckley/cabot-search huggingface dataset:
Increased activation of p38 MAPK in COPD
Authors: T. Renda, S. Baraldo, G. Pelaia, E. Bazzan, G. Turato, A. Papi, P. Maestrelli, R. Maselli, A. Vatrella, L. M. Fabbri, R. Zuin, S. A. Marsico, M. Saetta
Journal: European Respiratory Journal (2007)

Inflammation, oxidative stress and apoptosis, which are involved in chronic obstructive pulmonary disease (COPD) pathogenesis, may activate the p38 subgroup of mitogen-activated protein kinases (MAPKs). Therefore, the aim of the present study was to evaluate the expression of the phosphorylated, active form of p38 MAPK (phospho-p38) in the lungs of COPD patients. Surgical specimens were obtained from 18 smokers with COPD at different stages of disease severity, plus nine smoking and eight nonsmoking subjects with normal lung function. Phospho-p38+ cells were quantified by immunohistochemistry in both alveolar spaces and alveolar walls. Moreover, a Western blot analysis of phospho-p38 and total p38α isoform expressed by alveolar macrophages was performed. Phospho-p38+ alveolar macrophages and phospho-p38+ cells in alveolar walls were increased in patients with severe and mild/moderate COPD, compared with smoking and nonsmoking controls. Moreover, they were inversely correlated to values of forced expiratory volume in one second (FEV 1 ) and FEV 1 /forced vital capacity. Western blot analysis showed that phosphorylated p38, but not the total p38α isoform, was specifically increased in alveolar macrophages from COPD patients. Activation of the p38 mitogen-activated protein kinase pathway appears to be involved in the pathogenesis of chronic obstructive pulmonary disease. The present findings suggest that this protein may be a suitable pharmacological target for therapeutic intervention.
Phase I Trial of Preoperative Concurrent Doxorubicin and Radiation Therapy, Surgical Resection, and Intraoperative Electron-Beam Radiation Therapy for Patients With Localized Retroperitoneal Sarcoma
Authors: Peter W.T. Pisters, Matthew T. Ballo, Mark J. Fenstermacher, Barry W. Feig, Kelly K. Hunt, Kevin A. Raymond, Michael A. Burgess, Gunar K. Zagars, Raphael E. Pollock, Robert S. Benjamin, Shreyaskumar R. Patel
Journal: Journal of Clinical Oncology (2003)

Purpose: The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS). Patients and Methods: Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m 2 ) followed by a 4-day continuous infusion (4 mg/m 2 /d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy). Results: Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections. Conclusion: Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.
Long-term immunogenicity and efficacy of hepatitis B vaccine in infants born to HBeAg-positive HBsAg-carrier mothers
Authors: Kwang-Juei Lo, Shou-Dong Lee, Yang-Te Tsai, Tzee-Chung Wu, Cho-Yu Chan, Gran-Hum Chen, Ching-Lan Yeh
Journal: Hepatology (1988)

In an attempt to evaluate the long-term immunogenicity and efficacy of plasma-derived hepatitis B vaccine in preventing hepatitis B virus infection, 199 infants born to hepatitis B e antigen-positive hepatitis B surface antigen-carrier mothers were found to be antibody to HBsAg-positive (± 10 mIU per ml) 2 months after the first booster of hepatitis B vaccination at age 1, and their serum HBsAg and anti-HBs were rechecked annually to ages 3 to 5. Of the nine infants whose initial anti-HBs were low (10 to 100 mIU per ml) in concentration, four (44%) were found to be anti-HBs seronegative at age 3, while none of the 127 vaccine responders with high anti-HBs levels (&gt; 1,000 mlU per ml) lost their anti-HBs during the 4-year follow-up period. Also, in 63 infants whose initial anti-HBs titers were around 101 to 1,000 mIU per ml, only two lost their anti-HBs at age 4, and another two at age 5, respectively. Whether the vaccine responders lost their anti-HBs or not, no hepatitis B virus infection occurred in these vaccinees during the follow-up period. Thus, in the first 5 years of life, the protective efficacy in the high-risk infants who responded to plasma-derived hepatitis B vaccine was 100%. Because of the diversity of anti-HBs response in individuals, we suggest testing anti-HBs titer in all vaccinated infants after the first booster vaccination in order to calculate the time of next booster before the minimal protective level is reached.
Obstetric intensive care unit admission: a 2-year nationwide population-based cohort study
Authors: Joost J. Zwart, Just R. O. Dupuis, Annemiek Richters, Ferko Öry, Jos van Roosmalen
Journal: Intensive Care Medicine (2009)

As part of a larger nationwide enquiry into severe maternal morbidity, our aim was to assess the incidence and possible risk factors of obstetric intensive care unit (ICU) admission in the Netherlands.In a 2-year nationwide prospective population-based cohort study, all ICU admissions during pregnancy, delivery and puerperium (up to 42 days postpartum) were prospectively collected. Incidence, case fatality rate and possible risk factors were assessed, with special attention to the ethnic background of women.All 98 Dutch maternity units participated in the study. There were 847 obstetric ICU admissions in 358,874 deliveries, the incidence being 2.4 per 1,000 deliveries. Twenty-nine maternal deaths occurred, resulting in a case fatality rate of 1 in 29 (3.5%). Incidence of ICU admission varied largely across the country. Thirty-three percent of all cases of severe maternal morbidity were admitted to an ICU. Most frequent reasons for ICU admission were major obstetric haemorrhage (48.6%), hypertensive disorders of pregnancy (29.3%) and sepsis (8.1%). Assisted ventilation was needed in 34.8%, inotropic support in 8.8%. In univariable analysis, non-Western immigrant women had a 1.4-fold (95% CI 1.2-1.7) increased risk of ICU admission as compared to Western women. Initial antenatal care by an obstetrician was associated with a higher risk and home delivery with a lower risk of ICU admission.Population-based incidence of obstetric ICU admission in the Netherlands was 2.4 per 1,000 deliveries. Obstetric ICU admission accounts for only one-third of all cases of severe maternal morbidity in the Netherlands.
Chronic thromboembolic pulmonary hypertension: animal models
Authors: Olaf Mercier, Elie Fadel
Journal: European Respiratory Journal (2013)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease due to pulmonary artery obstruction by persistent organised clots related to one or more episodes of acute pulmonary embolism. To date, the pathogenesis of CTEPH remains unexplained. Pulmonary endarterectomy removes obstruction from pulmonary vessels and can cure patients. However, some unreachable distal pulmonary obstruction and/or associated distal pulmonary vasculopathy could induce persistent pulmonary hypertension, the main postoperative complication. The pathophysiology of CTEPH is not fully understood and improving knowledge of this disease could improve our future surgical and medical management. Many attempts, conducted over several decades, have failed to reproduce this chronic disease in animals. However, several animal models have provided insights into the pathophysiology and pathogenesis of CTEPH. Here, we review all the animal models that have improved the comprehension of CTEPH and hold promise for further investigations. This short review analyses strengths and weaknesses of all animal models available to study the pathophysiology of CTEPH.
Specific and Nonspecific Antitumor Immunity. I. Description of an In Vitro Assay Based on Inhibition of DNA Synthesis in Tumor Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: R M Williams, R N Germain, B Benacerraf
Journal: JNCI Journal of the National Cancer Institute (1975)

As in vitro assay of cell-mediated antitumor immunity based on the inhibition of tumor cell DNA synthesis (IDS) was devised. It was reasoned that both cytolytic and cytostatic antitumor effects could be measured in a quantitative yet generalized manner with this approach. By the use of microculture techniques and simplified methods for the determination of tritiated-thymidine incorporation by all cells in individual cultures, normal and immune effector (E) cell populations were compared in their ability to inhibit the DNA synthesis of a fixed initial number of various target tumor cells. Doubling dilutions of E cells were used to titrate the antitumor effects of normal and immune cells at many E/T (effector to target) ratios. Under conditions of alloimmunization, significant immunologically specific IDS effects could routinely be detected at an E/T ratio of less than 1 or 0.1:1, and under certain conditions at 1:100 or less. Results were highly reproducible with respect to the individual E cell donors, replicate cultures, and repeat experiments. The effects were proportional to visually determined cell destruction and independent of obvious culture artifacts. The IDS method was compared with the 51Cr release technique under various experimental conditions. The results demonstrated that decreases in E/T ratio and/or the addition of excess nonimmune cells to immune effector populations had a similar effect in both assays, which was to decrease the magnitude of the immune cell activity. Addition of excess normal cells reduced the activity of immune cells to a level below that of an equal number of immune cells tested at the same E/T ratio without added nonimmune cells. Both assays detected primarily a T lymphocyte-mediated lytic event when effectors generated by the described alloimmunizations were used. The IDS assay also detected a weak non-T-cell activity in anti-theta plus complement-treated alloimmune spleen. The possibility that this represented antibody-dependent cell-mediated cytotoxicity was raised by the finding that normal spleen ceels plus antitarget antibody had significant activity in the IDS system. The sensitivities of the two methods were compared and the potential of the IDS method was evaluated.
Total endoscopic eradication of Barrett's esophagus: Study methodology, candidate selection, and clinical outcomes
Authors: N. Shaheen, S. Spechler
Journal: Endoscopy (2008)

This issue of Endoscopy focuses on total endoscopic eradication of Barrett's esophagus, a condition described by the Australian surgeon Norman Rupert Barrett in 1950 [1] . This paper considers methodological aspects of studies of ablative therapies for Barrett's esophagus, and how the choices made by investigators with respect to study methodology and candidate selection might impact the clinical outcomes observed in these studies.
Diagnostic and treatment behaviour in children with chronic respiratory symptoms: relationship with socioeconomic factors
Authors: G Ng Man Kwong
Journal: Thorax (2002)

<b>Background:</b> The prevalence and severity of asthma is believed to increase with increasing socioeconomic deprivation. The relationship between asthma diagnosis, symptoms, diagnostic accuracy, and socioeconomic deprivation as determined by Townsend scores was determined in Sheffield schoolchildren. <b>Methods:</b> All 6021 schoolchildren aged 8–9 years in one school year in Sheffield were given a parent respondent survey based on International Survey of Asthma and Allergies in Childhood (ISAAC) questions. <b>Results:</b> 5011/6021 (83.2%) questionnaires were returned. Postcode data were available in 4131 replies (82.4%) and were used to assign a composite deprivation score (Townsend score). Scores were divided into five quintiles, with group 1 being least and group 5 being most deprived. A positive trend was observed from group 1 to group 5 for the prevalence of wheeze in the previous 12 months, wheeze attacks ≥4/year, nocturnal wheeze and cough (all p&lt;0.001), cough and/or wheeze "most times" with exertion (p&lt;0.03), current asthma (p&lt;0.001), and significant asthma symptoms (p&lt;0.001). No significant trend was observed for lifetime wheeze or attacks of speech limiting wheeze. There were no significant trends in the prevalence of current asthmatic children without significant symptoms (overdiagnosis) or children with significant asthma symptoms but no current asthma diagnosis (underdiagnosis) across the social groups. There was a significant negative trend in the ratio of asthma medication to asthma diagnosis from least to most deprived groups (p&lt;0.001). <b>Conclusions:</b> Asthma morbidity and severity increase according to the level of socioeconomic deprivation. This may be due to differences in environment, asthma management, and/or symptom reporting. Diagnostic accuracy does not vary significantly across deprivation groups but children living in areas of least deprivation and taking asthma medication are less likely to be labelled as having asthma, suggesting diagnostic labelling bias.
Paradoxical Decrease in the Capture and Lymph Node Delivery of Cancer Vaccine Antigen Induced by a TLR4 Agonist as Visualized by Dual-Mode Imaging
Authors: Deepak K. Kadayakkara, Michael J. Korrer, Jeff W.M. Bulte, Hyam I. Levitsky
Journal: Cancer Research (2014)

Traditionally, cell-mediated immune responses to vaccination in animal models are evaluated by invasive techniques such as biopsy and organ extraction. We show here that by combining two noninvasive imaging technologies, MRI and bioluminescence imaging (BLI), we can visualize both the afferent and efferent arms of cellular events following vaccination longitudinally. To this end, we evaluated the immune response elicited by a novel Toll-like receptor 4 agonist vaccine adjuvant, glucopyranosyl lipid A (GLA), using a whole-cell tumor vaccine. After magnetovaccination, MRI was used to visualize antigen-presenting cell-mediated antigen capture and subsequent migration to draining lymph nodes (DLN). Paradoxically, we observed that the incorporation of GLA in the vaccine reduced these critical parameters of the afferent immune response. For the efferent arm, the magnitude of the ensuing antigen-specific T-cell response in DLN visualized using BLI correlated with antigen delivery to the DLN as measured by MRI. These findings were confirmed using flow cytometry. In spite of the GLA-associated reduction in antigen delivery to the DLN, however, the use of GLA as a vaccine adjuvant led to a massive proliferation of vaccine primed antigen-specific T cells in the spleen. This was accompanied by an enhanced tumor therapeutic effect of the vaccine. These findings suggest that GLA adjuvant changes the temporal and anatomical features of both the afferent and efferent arms of the vaccine response and illustrates the utility of quantitative noninvasive imaging as a tool for evaluating these parameters during vaccine optimization.
149 THE MANNAN-BINDING LECTIN-ASSOCIATED SERINE PROTEASE-2 D120G MUTATION IS A COMMON PATHOPHYSIOLOGICAL DENOMINATOR FOR NON-ANASTOMOTIC BILIARY STRICTURES AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND THE BUDD–CHIARI SYNDROME
Authors: B.-J. de Rooij, K. Sebib Korkmaz, H. Verspaget, M. Coenraad, R. Porte, B. van Hoek
Journal: Journal of Hepatology (2013)
Premedication with 20 mg dexamethasone effectively prevents relapse of extensive skin rash associated with gemcitabine monotherapy
Authors: M. Kanai, S. Matsumoto, T. Nishimura, Y. Matsumura, E. Hatano, A. Mori, T. Masui, Y. Kawaguchi, E. Nakamura, S. Tada, T. Kitano, H. Ishiguro, K. Yanagihara, T. Chiba
Journal: Annals of Oncology (2009)
Getting out and about with arthritis: or not?
Authors: M A Chamberlain
Journal: Annals of the Rheumatic Diseases (1991)

<h3>ABSTRACT</h3> Group B Streptococcus agalactiae (GBS; Streptococcus agalactiae) is the most common cause of neonatal meningitis and a rising cause of sepsis in adults. Recently, it has also been shown to cause foodborne disease. As with many other bacteria, the polysaccharide capsule of GBS is antigenic, enabling its use for strain serotyping. Recent advances in DNA sequencing have made sequence-based typing attractive (as has been implemented for several other bacteria, including <i>Escherichia coli, Klebsiella pneumoniae</i> species complex, <i>Streptococcus pyogenes</i>, and others). For GBS, existing WGS-based serotyping systems do not provide complete coverage of all known GBS serotypes (specifically including subtypes of serotype III), and none are simultaneously compatible with the two most common data types, raw short reads and assembled sequences. Here, we create a serotyping database (GBS-SBG, GBS Serotyping by Genome Sequencing), with associated scripts and running instructions, that can be used to call all currently described GBS serotypes, including subtypes of serotype III, using both direct short-read- and assembly-based typing. We achieved higher concordance using GBS-SBG on a previously reported data set of 790 strains. We further validated GBS-SBG on a new set of 572 strains, achieving 99.8% concordance with PCR-based molecular serotyping using either short-read- or assembly-based typing. The GBS-SBG package is publicly available and will accelerate and simplify serotyping by sequencing for GBS. <h3>DATA SUMMARY</h3> The GBS-SBG package is open source and available for at Github under the MIT license (URL - https://github.com/swainechen/GBS-SBG) Accession numbers of the sequencing reads and reference sequences used in the study from earlier reports have been provided within the article and the supplementary data The WGS data for the 572 isolates used in the study is available at https://www.ncbi.nlm.nih.gov/bioproject/PRJNA293392
Extended Prognostic Value of Urinary Albumin Excretion for Cardiovascular Events
Authors: Auke H. Brantsma, Stephan J.L. Bakker, Dick de Zeeuw, Paul E. de Jong, Ronald T. Gansevoort
Journal: Journal of the American Society of Nephrology (2008)

Because urinary albumin excretion (UAE) is a marker of cardiovascular (CV) risk, some have proposed screening the general population; however, it is unknown how the predictive power of a single screening value changes over time. In this study, data of 8496 individuals in a community-based, prospective cohort were used to evaluate this question. For each doubling of baseline UAE, the hazard ratio (HR) for a CV event was 1.36 (95% confidence interval [CI] 1.31 to 1.42). Baseline UAE similarly predicted events occurring >5 yr after baseline, suggesting that it remains a good predictor during at least the first 5 yr after measurement. Approximately 4 yr after baseline, UAE was measured again in 6800 individuals. Once again, high UAE (>75th percentile) predicted subsequent CV events, whether defined using the baseline UAE or follow-up UAE (HR 3.39 [95% CI 2.58 to 4.45] and HR 2.50 [95% CI] 1.90 to 3.29, respectively; P = 0.3 for difference). Finally, compared with individuals with consistently low UAE, individuals who progressed from low to high UAE during follow-up had a significantly higher risk for CV events (HR 3.68; 95% CI 2.45 to 5.53). In conclusion, UAE remains a good predictor of CV events during the first 5 yr after measurement, but repeating the measurement several years later also detects progression of UAE, which is also associated with increased CV risk. Future studies are required to determine the optimal interval of repeat testing and its cost-effectiveness.
Peroxisome proliferator-activated receptor ligands for airway diseases?
Authors: K Parameswaran
Journal: Thorax (2003)

▴ Patel HJ, Belvisi MG, Bishop-Bailey D, et al . Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol2003;170:2663–9 [OpenUrl][1][Abstract/FREE Full Text][2] The peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors belonging to the hormone receptor family. The alpha and gamma subtypes are predominantly expressed in liver, muscle, and adipose tissues where, when activated by ligands such … [1]: {openurl}?query=rft.jtitle%253DThe%2BJournal%2Bof%2BImmunology%26rft.stitle%253DJ.%2BImmunol.%26rft.issn%253D0022-1767%26rft.aulast%253DPatel%26rft.auinit1%253DH.%2BJ.%26rft.volume%253D170%26rft.issue%253D5%26rft.spage%253D2663%26rft.epage%253D2669%26rft.atitle%253DActivation%2Bof%2BPeroxisome%2BProliferator-Activated%2BReceptors%2Bin%2BHuman%2BAirway%2BSmooth%2BMuscle%2BCells%2BHas%2Ba%2BSuperior%2BAnti-inflammatory%2BProfile%2Bto%2BCorticosteroids%253A%2BRelevance%2Bfor%2BChronic%2BObstructive%2BPulmonary%2BDisease%2BTherapy%26rft_id%253Dinfo%253Adoi%252F10.4049%252Fjimmunol.170.5.2663%26rft_id%253Dinfo%253Apmid%252F12594295%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jimmunol&resid=170/5/2663&atom=%2Fthoraxjnl%2F58%2F6%2F542.atom
PCBP-1 regulates alternative splicing of the CD44 gene and inhibits invasion in human hepatoma cell line HepG2 cells
Authors: Tong Zhang, Xian-Hong Huang, Lan Dong, Deqing Hu, Changhui Ge, Yi-Qun Zhan, Wang-Xiang Xu, Miao Yu, Wei Li, Xiaohui Wang, Liujun Tang, Chang-Yan Li, Xiao-Ming Yang
Journal: Molecular Cancer (2010)

Abstract Background PCBP1 (or alpha CP1 or hnRNP E1), a member of the PCBP family, is widely expressed in many human tissues and involved in regulation of transcription, transportation process, and function of RNA molecules. However, the role of PCBP1 in CD44 variants splicing still remains elusive. Results We found that enforced PCBP1 expression inhibited CD44 variants expression including v3, v5, v6, v8, and v10 in HepG2 cells, and knockdown of endogenous PCBP1 induced these variants splicing. Invasion assay suggested that PCBP1 played a negative role in tumor invasion and re-expression of v6 partly reversed the inhibition effect by PCBP1. A correlation of PCBP1 down-regulation and v6 up-regulation was detected in primary HCC tissues. Conclusions We first characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.
Intracellular residency of Staphylococcus aureus within mast cells in nasal polyps: A novel observation
Authors: Stephen M. Hayes, Robert Howlin, David A. Johnston, Jeremy S. Webb, Stuart C. Clarke, Paul Stoodley, Philip G. Harries, Susan J. Wilson, Sylvia L.F. Pender, Saul N. Faust, Luanne Hall-Stoodley, Rami J. Salib
Journal: Journal of Allergy and Clinical Immunology (2015)