tbuckley/cabot-search huggingface dataset:
Usefulness of exhaled breath condensate as non-invasive method of evaluating of biomarkers in severe asthma patients
Authors: Patrycja Nejman-Gryz, Joanna Hermanowicz-Salamon, Malgorzata Proboszcz, Magdalena Paplinska-Goryca, Renata Rubinsztajn, Ryszarda Chazan
Journal: European Respiratory Journal (2014)

Exhaled breath condenstae (EBC) is a non-invasive, easily performed method for obtaining samples from respiratory tract. The use of EBC may be of great importance in patients with severe asthma, because of the difficulty in sputum induction (IS) in these patients.  The aim of our experiments was to determine the concentrations of selected cytokines in IS and EBC and verify the hypothesis that in patients with severe asthma sputum induction may be omitted for the EBC.  The study enrolled 17 patients with severe asthma who underwent sputum induction and EBC. Patients were free from acute exacerbations, but they received steroids therapy. The respiratory specimens were stored at -80 °C, and EBC was not densified. The concentration of IL-6, IL-13, TNF-α, TSLP, CCL-24 and IFNγ was determined in all samples with ELISA tests .  The obtained results are presented in the table.  The concentration of IL-13, TNF-α and TSLP were comparable in IS and EBC. Unexpectedly high levels of IFNγ in asthma patients in both IS and EBC may due to therapy, because steroid treatment may result in elevation of these markers. High significantly greater concentration of IL-6 and CCL-24 in IS vs. EBC was probably depended on the recovery of mucosal deposits of these markers during extraction of sputum.  The results of our study have confirmed the usefulness of EBC for analyze IL-13, and TNF α. The sputum samples seems to be better in analyze of IL-6 and definitely only one a good enough source of CCL-24.
miRNA Nomenclature: A View Incorporating Genetic Origins, Biosynthetic Pathways, and Sequence Variants
Authors: T. Desvignes, P. Batzel, E. Berezikov, K. Eilbeck, J.T. Eppig, M.S. McAndrews, A. Singer, J.H. Postlethwait
Journal: Trends in Genetics (2015)
Controlled evaluation of three drug combination regimens versus fluorouracil alone for the therapy of advanced gastric cancer. North Central Cancer Treatment Group.
Authors: S A Cullinan, C G Moertel, H S Wieand, M J O'Connell, M A Poon, J E Krook, J A Mailliard, L K Tschetter
Journal: Journal of Clinical Oncology (1994)

PURPOSE The purpose of this study was to evaluate the therapeutic effectiveness of fluorouracil (5-FU), doxorubicin, and methyl lomustine (CCNU) (FAMe), 5-FU, doxorubicin, and cisplatin (FAP), and FAMe alternating with triazinate (TZT) when compared with a standard therapy of 5-FU alone in patients with advanced gastric cancer. PATIENTS AND METHODS Two hundred fifty-two eligible patients selected for study had proven locally unresectable and/or metastatic gastric adenocarcinoma. The majority had nonmeasureable disease. They were randomly assigned to receive one of the three drug combination regimens or to 5-FU alone administered by rapid injection in 5-day course. Survival was the primary study end point. RESULTS None of the three drug combinations showed a significant advantage over 5-FU alone in improved performance score, weight gain, or patient survival. Each of the three combinations was more toxic than 5-FU alone. CONCLUSION FAMe, FAP, or FAMe alternating with TZT cannot be recommended for the therapy of advanced gastric carcinoma. Therapy of this disease should remain an experimental endeavor. It would seem reasonable to prove the value of any new treatment approach by a randomized comparison to simple therapy with 5-FU alone.
Cardiovascular safety of ustekinumab in patients with moderate to severe psoriasis: results of integrated analyses of data from phase II and III clinical studies
Authors: K. Reich, R.G. Langley, M. Lebwohl, P. Szapary, C. Guzzo, N. Yeilding, S. Li, M-C. Hsu, C.E.M. Griffiths
Journal: British Journal of Dermatology (2011)

Background Patients with psoriasis are believed to be at an increased risk of cardiovascular (CV) morbidity, and the effect of biological agents on CV safety is not fully understood. Objectives To evaluate the effect of ustekinumab on CV events using detailed analyses of pooled data from the phase II/III clinical studies of its use in moderate to severe psoriasis. Methods The incidence of major adverse CV events [MACE: myocardial infarction (MI), stroke or CV death] is reported. Meta‐analyses using risk difference and odds ratio estimates are presented based on data collected during the placebo‐controlled period of ustekinumab trials. The cumulative numbers of events and rates of MIs and strokes over time were compared with those expected in the psoriasis and/or general populations. Results During the placebo‐controlled period (12/20 weeks), five MACE were reported in 1582 ustekinumab‐treated patients [0·3%; 95% confidence interval (CI) 0·1–0·7%] compared with no events in 732 placebo‐treated patients (0·0%; 95% CI 0·0–0·5%). MACE rates were stable over time during both the controlled and uncontrolled study periods, with 19 of 3117 ustekinumab‐treated patients (0·6%) experiencing 21 events for a combined event rate per 100 patient‐years of follow‐up of 0·44 (95% CI 0·27–0·67) through up to 3 years. Standardized incidence ratios for comparison of ustekinumab clinical data with external data sources ranged from 0·34 to 0·52, suggesting no increased risk of MI or stroke in ustekinumab‐treated patients compared with the general U.S. and psoriasis populations. Conclusions The totality of available clinical data suggests neither a detrimental nor a beneficial effect of ustekinumab on serious CV events. Additional data are needed to define the net effect of ustekinumab on CV events.
Gender discrepancies in living related renal transplant donors and recipients.
Authors: W E Bloembergen, F K Port, E A Mauger, J P Briggs, A B Leichtman
Journal: Journal of the American Society of Nephrology (1996)

Renal transplantation is the most successful treatment strategy for patients with ESRD to improve survival and quality of life. The study presented here examines the relationship of gender and living related (LR) transplantation donor and recipient rates in the United States. National data from the United States Renal Data System (USRDS) were used for this study. All LR transplants occurring between 1991 and 1993 among blacks and whites were included (N = 6193). Transplantation and donation rates for men and women were calculated. Poisson regression was used to calculate female/male transplantation and donation rate ratios. Overall, women were 10% less likely to receive a LR transplant than men (rate ratio [RR] = 0.90, P < 0.001). This gender difference increased over time from 1991 (Female/Male RR = 0.95, P = not significant [NS]) to 1993 (RR = 0.85, P < 0.001). In contrast, women were significantly more likely to donate a kidney than men (RR = 1.28, P < 0.001 and RR = 1.29, P < 0.001 among whites and blacks, respectively). Analyses by age subgroups revealed that only among ESRD patients aged 20 to 44 yr was the likelihood of receiving a LR kidney transplant equal for men and women. Higher donation rates among women compared with men were observed in all donor age and race subgroups except young blacks (aged 0 to 19 yr). Recipient gender appeared to influence donation rates. The female-to-male relative donation rates were higher when donations were to female, compared with male, recipients. This study of national data suggests an imbalance in LR donation and transplantation between men and women. Women are more likely to donate a kidney but are less likely to receive a LR transplant than men. Several potential explanatory factors are explored. These findings suggest a need for the development of gender-appropriate interventions to encourage donation among men and LR transplantation among women, to ultimately facilitate greater use of this ESRD treatment modality.
Measles—United States, January 1–April 25, 2008
Authors: Nakia S Clemmons, Paul A Gastanaduy, Amy Parker Fiebelkorn, Susan B Redd, Gregory S Wallace
Journal: JAMA (2008)

Measles is a highly contagious, acute viral illness that can lead to complications such as pneumonia, encephalitis, and death. As a result of high 2-dose measles vaccination coverage in the United States and improved control of measles in the World Health Organization's Region of the Americas, the United States declared measles elimination (defined as interruption of year-round endemic transmission) in 2000. Importations from other countries where measles remains endemic continue to occur, however, which can lead to clusters of measles cases in the United States. To update surveillance data on current measles outbreaks, CDC analyzed cases reported during January 4-April 2, 2015. A total of 159 cases were reported during this period. Over 80% of the cases occurred among persons who were unvaccinated or had unknown vaccination status. Four outbreaks have occurred, with one accounting for 70% of all measles cases this year. The continued risk for importation of measles into the United States and occurrence of measles cases and outbreaks in communities with high proportions of unvaccinated persons highlight the need for sustained, high vaccination coverage across the country.
Cytotoxicity of Antiviral Nucleotides Adefovir and Cidofovir Is Induced by the Expression of Human Renal Organic Anion Transporter 1
Authors: EDMUND S. HO, DEBORAH C. LIN, DIRK B. MENDEL, TOMAS CIHLAR
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The transport of organic anions in proximal convoluted tubules plays an essential role in the active secretion of a variety of small molecules by the kidney. In addition to other anionic substrates, the human renal organic anion transporter 1 (hOAT1) is capable of transporting the nucleotide analogs adefovir and cidofovir. To investigate the involvement of hOAT1 in the mechanism of nephrotoxicity associated with these two clinically important antiviral agents, Chinese hamster ovary (CHO) cells were stably transfected with hOAT1 cDNA. The resulting CHO hOAT cells showed probenecid-sensitive and pH-dependent uptake of p -aminohippurate ( K m = 15.4 μM, V max = 20.6 pmol/10 6 cells · min), a prototypical organic anion substrate. In addition, the stably expressed hOAT1 mediated efficient transport of adefovir ( K m = 23.8 μM, V max = 46.0 pmol/10 6 cells · min) and cidofovir ( K m = 58.0 μM, V max = 103 pmol/10 6 cells · min) such that the levels of intracellular metabolites of both nucleotides were &gt;100-fold higher in CHO hOAT cells than in parental CHO. Consequently, adefovir and cidofovir were approximately 500-fold and 400-fold more cytotoxic, respectively, in CHO hOAT cells compared to CHO. The cytotoxicity of both drugs in CHO hOAT cells was markedly reduced in the presence of hOAT1 inhibitors. The cyclic prodrug of cidofovir, which exhibits reduced in vivo nephrotoxicity, was a poor substrate for hOAT1 and showed only marginally increased cytotoxicity in CHO hOAT cells. In conclusion, these studies demonstrate that hOAT1 plays a critical role in the organ-specific toxicity of adefovir and cidofovir, and indicates that CHO hOAT cells may represent a useful in vitro model to investigate the potential nephrotoxicity of clinically relevant organic anion agents.
In Vivo Antigenic Modification of Tumor Cells. II. Distribution of Virus in Sarcoma-Bearing Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J D Iglehart, E C Ward, G Huper, K Thiel, D P Bolognesi
Journal: JNCI Journal of the National Cancer Institute (1981)

Murine leukemia viruses were previously demonstrated to be able to infect efficiently non-virus-expressing tumors in vivo. In the present study the infectivity and tissue distribution of Friend murine leukemia virus (F-MuLV) in normal and tumor-bearing C57BL/6J (B6) mice were examined. Two syngeneic fibrosarcoma-inducing cell lines were used: Cells from a 3-methylcholanthrene-induced fibrosarcoma syngeneic to B6 mice (MCA-FS) and cells from a Harvey murine sarcoma virus-transformed, nonproducer sarcoma syngeneic to B6 mice (H-NP) were described in the preceding study. Both cell lines lacked ecotropic viral expression. F-MuLV produced in vitro was rarely able to infect normal adult B6 tissue in vivo and lacked pathogenic potential. Adult animals receiving F-MuLV remained clinically normal during 20 months of follow-up and had no detectable viremia, although some had persistently infected thymuses and long bones. In animals receiving a single dose of F-MuLV given to superinfect either the MCA-FS or the H-NP induced tumors, virion antigens were found only in tumor tissue and not in the normal host organs studied. Infectious virus was abundant in tumors; occasionally, it was found in thymuses and long bones of animals bearing superinfected H-NP tumors but rarely in other organs. Localization of F-MuLV in MCA-FS tumors appeared to be more selective with rare contamination of host organs. The presence of a rescuable sarcoma genome in H-NP may explain the discrepancy between MCA-FS and H-NP tumors. The possibility of increasing the efficiency and selectivity of infection as well as the therapeutic application of this technique are discussed.
Prescription Information Leaflets: A National Survey
Authors: S Gibbs, W E Waters, C F George
Journal: Journal of the Royal Society of Medicine (1990)

Three thousand four hundred and ten patients recruited at 254 pharmacies took part in a national postal survey of the effect of prescription information leaflets. The patients had been prescribed penicillins, non-steroidal anti-inflammatory drugs (NSAIDs) or β-adrenoceptor antagonists. The 1809 patients who received leaflets knew more about their medicines, especially the side effects and were significantly more satisfied than the 1601 patients who were not given additional written information. The leaflets were found to be effective when issued in the north, in the south and in small, medium and large towns. Patients of both sexes, all age groups and social classes were found to benefit from the leaflets and almost everyone (97%) thought they were a good idea. These results confirm and extend our previous findings and add further support for the routine use of information leaflets with prescribed medicines.
Transcriptome Sequencing of the Anterior Cingulate in Bipolar Disorder: Dysregulation of G Protein-Coupled Receptors
Authors: Cristiana Cruceanu, Powell Patrick Cheng Tan, Sanja Rogic, Juan Pablo Lopez, Susana Gabriela Torres-Platas, Carolina O. Gigek, Martin Alda, Guy A. Rouleau, Paul Pavlidis, Gustavo Turecki
Journal: American Journal of Psychiatry (2015)

Gene expression dysregulation in the brain has been associated with bipolar disorder through candidate gene and microarray expression studies, but questions remain about isoform-specific dysregulation and the role of noncoding RNAs whose importance in the brain has been suggested recently but not yet characterized for bipolar disorder.The authors used RNA sequencing, a powerful technique that captures the complexity of gene expression, in postmortem tissue from the anterior cingulate cortex from 13 bipolar disorder case subjects and 13 matched comparison subjects. Differential expression was computed, and a global pattern of downregulation was detected, with 10 transcripts significant at a false discovery rate ≤5%. Importantly, all 10 genes were also replicated in an independent RNA sequencing data set (N=61) from the anterior cingulate cortex.Among the most significant results were genes coding for class A G protein-coupled receptors: SSTR2 (somatostatin receptor 2), CHRM2 (cholinergic receptor, muscarinic 2), and RXFP1 (relaxin/insulin-like family peptide receptor 1). A gene ontology analysis of the entire set of differentially expressed genes pointed to an overrepresentation of genes involved in G protein-coupled receptor regulation. The top genes were followed up by querying the effect of treatment with mood stabilizers commonly prescribed in bipolar disorder, which showed that these drugs modulate expression of the candidate genes.By using RNA sequencing in the postmortem bipolar disorder brain, an interesting profile of G protein-coupled receptor dysregulation was identified, several new bipolar disorder genes were indicated, and the noncoding transcriptome in bipolar disorder was characterized. These findings have important implications with regard to fine-tuning our understanding of the bipolar disorder brain, as well as for identifying potential new drug target pathways.
Role of IL-1α and IL-1β in cigarette smoke-induced pulmonary inflammation and COPD
Authors: Ken Bracke, Nele Pauwels, Lisa Dupont, Geert Van Pottelberge, Guy Joos, Guy Brusselle
Journal: European Respiratory Journal (2011)

Signalling through the IL-1 Receptor-I (IL-1RI) is critical in the pulmonary inflammation induced by cigarette smoke (CS). Although several reports implicate IL-1β in the pathogenesis of COPD, it remains unclear whether IL-1α or IL-1β is the predominant ligand for IL-1RI in CS-induced inflammation.

C57BL/6 mice were exposed to air or CS for 3 days (acute exposure) and were treated on day 1 and 3 with an intravenous injection of 40μg anti-IL-1α, anti-IL-1β or hamster IgG isotype control. 24h after the last exposure, we evaluated the presence of inflammatory cells in the bronchoalveoalar lavage (BAL) fluid. In a translational study, we measured the levels of IL-1α and IL-1β mRNA (in total lung tissue by RT-PCR) and protein (in induced sputum by ELISA) of never smokers, smokers without COPD and patients with COPD.

Acute exposure to CS resulted in a significant increase in BAL neutrophils in isotype treated mice. In contrast, this CS-induced BAL neutrophilia was significantly attenuated in both anti-IL-1α and anti-IL-1β treated mice. Interestingly, we found increased mRNA and protein levels of IL-1α and IL-1β in lung tissue and induced sputum of patients with COPD, compared to never-smokers (Table 1).

View this table:

Table 1. Human IL-1α and IL-1β levels





These results suggest that not only IL-1β, but also IL-1α should be considered important in CS-induced inflammation.
The interplay between gastric cancer cell lines and PBMCs mediated by the CC chemokine RANTES plays an important role in tumor progression.
Authors: K Okita, T Furuhata, Y Kimura, M Kawakami, K Yamaguchi, T Tsuruma, H Zembutsu, K Hirata
Journal: Journal of experimental & clinical cancer research (2005)

In the present study, we investigated the effect of the RANTES-mediated interaction between gastric carcinoma cell lines and peripheral blood mononuclear cells (PBMCs) in tumor progression. RANTES production in PBMCs stimulated by highly metastatic cancer cell line-conditioned supernatants was higher than in those stimulated by a less metastatic gastric cancer cell line-conditioned supernatant. RANTES receptors were expressed in PBMCs, but not in those cancer cell lines; therefore it was suggested that RANTES might affect PBMCs but not cancer cells. Matrix metalloproteinase (MMP)-9 expression in PBMCs was examined. Similar to RANTES production, MMP-9 expression in PBMCs stimulated by highly metastatic cell line-conditioned supernatants was higher than in that stimulated by a less metastatic cell line-conditioned supernatant. Invasion assays of gastric cancer cell lines were performed. Cancer cells cultured with PBMCs invaded into Matrigel more frequently than those without PBMCs. This invasive activity was highly inhibited by an anti-RANTES antibody. These results suggest that tumor cells can acquire the potential for invasion by cooperating with PBMCs and RANTES plays an important role in the interplay between tumor cells and PBMCs. It is thus thought that RANTES might be a candidate molecular target in the therapeutic strategy for gastric cancers.
Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on Immune Response
Authors: Lisa A. Jackson, James D. Campbell, Sharon E. Frey, Kathryn M. Edwards, Wendy A. Keitel, Karen L. Kotloff, Andrea A. Berry, Irene Graham, Robert L Atmar, C. Buddy Creech, Isaac P. Thomsen, Shital M. Patel, Andres F. Gutierrez, Edwin L. Anderson, Hana M. El Sahly, Heather Hill, Diana L. Noah, Abbie R. Bellamy
Journal: JAMA (2015)

<h3>Importance</h3> Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continue to occur. Hemagglutinin H7 administered alone is a poor immunogen necessitating evaluation of adjuvanted H7N9 vaccines. <h3>Objective</h3> To evaluate the immunogenicity and safety of an inactivated H7N9 vaccine with and without AS03 adjuvant, as well as mixed vaccine schedules that included sequential administration of AS03- and MF59-containing formulations and of adjuvanted and unadjuvanted formulations. <h3>Design, Setting, and Participants</h3> Double-blind, phase 2 trial at 5 US sites enrolled 980 adults aged 19 through 64 years from September 2013 through November 2013; safety follow-up was completed in January 2015. <h3>Interventions</h3> The H7N9 vaccine was given on days 0 and 21 at nominal doses of 3.75 µg, 7.5 µg, 15 µg, and 45 µg of hemagglutinin with or without AS03 or MF59 adjuvant mixed on site. <h3>Main Outcomes and Measures</h3> Proportions achieving a hemagglutination inhibition antibody (HIA) titer of 40 or higher at 21 days after the second vaccination; vaccine-related serious adverse events through 12 months after the first vaccination; and solicited signs and symptoms after vaccination through day 7. <h3>Results</h3> Two doses of vaccine were required to induce detectable antibody titers in most participants. After 2 doses of an H7N9 formulation containing 15 µg of hemagglutinin given without adjuvant, with AS03 adjuvant, or with MF59 adjuvant, the proportion achieving an HIA titer of 40 or higher was 2% (95% CI, 0%-7%) without adjuvant (n = 94), 84% (95% CI, 76%-91%) with AS03 adjuvant (n = 96), and 57% (95% CI, 47%-68%) with MF59 adjuvant (n = 92) (<i>P</i> &lt; .001 for comparison of the AS03 and MF59 schedules). The 2 schedules alternating AS03-and MF59-adjuvanted formulations led to lower geometric mean titers (GMTs) of (41.5 [95% CI, 31.7-54.4]; n = 92) and (58.6 [95% CI, 44.3-77.6]; n = 96) than the group induced by 2 AS03-adjuvanted formulations (n = 96) (103.4 [95% CI, 78.7-135.9];<i>P</i> &lt; .001) but higher GMTs than 2 doses of MF59-adjuvanted formulation (n = 94) (29.0 [95% CI, 22.4-37.6];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The AS03 and MF59 adjuvants augmented the immune responses to 2 doses of an inactivated H7N9 influenza vaccine, with AS03-adjuvanted formulations inducing the highest titers. This study of 2 adjuvants used in influenza vaccine formulations with adjuvant mixed on site provides immunogenicity information that may be informative to influenza pandemic preparedness programs. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01942265