tbuckley/cabot-search huggingface dataset:
Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in 5-9-year-old Indonesian children
Authors: None Suharyono, C Simanjuntak, H Totosudirjo, N Witham, N Punjabi, D Burr, K Sorenson, D.G Heppner, G Losonsky, J Clemens, Y.L Lim, S.S Wasserman, J Kaper, M.M Levine, A.R Rifai, S Cryz
Journal: The Lancet (1992)
Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases
Authors: Y. Vinogradova, C. Coupland, J. Hippisley-Cox
Journal: BMJ (2015)

<b>Objective</b> To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account. <b>Design</b> Two nested case-control studies. <b>Setting</b> General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices). <b>Participants</b> Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year. <b>Main outcome measures</b> Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets. <b>Results</b> 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10 000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17). <b>Conclusions</b> In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.
Identification of Hematopoietic Stem Cell–Specific miRNAs Enables Gene Therapy of Globoid Cell Leukodystrophy
Authors: Bernhard Gentner, Ilaria Visigalli, Hidefumi Hiramatsu, Eric Lechman, Silvia Ungari, Alice Giustacchini, Giulia Schira, Mario Amendola, Angelo Quattrini, Sabata Martino, Aldo Orlacchio, John E. Dick, Alessandra Biffi, Luigi Naldini
Journal: Science Translational Medicine (2010)

Hematopoietic stem cell–specific microRNAs allow regulation of therapeutic transgene expression and enable effective gene therapy of globoid cell leukodystrophy.
Cytokine formation within rat glomeruli during experimental endotoxemia.
Authors: B Fouqueray, C Philippe, A Herbelin, J Perez, R Ardaillou, L Baud
Journal: Journal of the American Society of Nephrology (1993)

Increasing evidence supports a role of cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and IL-6 in the development of endotoxin-induced acute renal failure. Several activities of these cytokines require a local rather than a systemic production and function. Thus, this study investigates the chronology of cytokine expression in glomeruli isolated from normal rats or rats given iv lipopolysaccharide injections. Detectable levels of TNF alpha could be found in glomeruli isolated from normal rats as assessed by L-929 fibroblast lytic assay and ELISA. Glomeruli isolated from rats given lipopolysaccharide transiently released increased amounts of TNF alpha in relation to the dose of lipopolysaccharide (10 to 500 micrograms/kg body wt) and the lag period between lipopolysaccharide injection and glomerular isolation (20 to 120 min). TNF alpha was released in similar amounts by glomeruli from normal rats that were exposed in vitro to lipopolysaccharide challenge (0.01 to 10 micrograms/mL), indicating that lipopolysaccharide had direct effects on the release of TNF alpha from glomerular cells. These cells consisted mainly of resident cells because reduction of glomerular infiltration by bone marrow-derived cells after the irradiation of normal rats did not affect TNF alpha release. Glomerular IL-1 and IL-6 production was evaluated by specific bioassays under identical conditions. No IL-1 activity could be detected in the medium or within the glomerular cells at any time within 120 min after lipopolysaccharide injection. By contrast, glomerular IL-6 production was induced after lipopolysaccharide challenge both in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
The complexity-cost factor in bilingualism
Authors: Julia Festman
Journal: Behavioral and Brain Sciences (2013)

Abstract Language processing changes with the knowledge and use of two languages. The advantage of being bilingual comes at the expense of increased processing demands and processing costs. I suggest considering bilingual complexity including these demands and costs. The proposed model claims effortless monolingual processing. By integrating individual and situational variability, the model would lose its idealistic touch, even for monolinguals.
Role of transient receptor potential and pannexin channels in cigarette smoke-triggered ATP release in the lung
Authors: Matthew Baxter, Suffwan Eltom, Bilel Dekkak, Liang Yew-Booth, Eric D Dubuis, Sarah A Maher, Maria G Belvisi, Mark A Birrell
Journal: Thorax (2014)

COPD is an inflammatory disease usually associated with cigarette smoking (CS) with an increasing global prevalence and no effective medication. Extracellular ATP is increased in the COPD affected lung and may play a key role in driving CS-induced airway inflammation, but the mechanism involved in ATP release has eluded researchers. Recently, the transient receptor potential (TRP) and pannexin-1 channels have been suggested to play a role in other experimental paradigms. Thus, the aim of this work is to investigate if these channels are involved in CS-induced ATP release in the lung.Primary human cells were exposed to CS and extracellular ATP levels measured. Mice were exposed to mainstream CS and airway inflammation assessed. TRPV1/4 mRNA expression was assessed in human lung parenchyma.CS exposure caused a dose-related increase in ATP from primary airway bronchial epithelial cells. This was attenuated by blockers of TRPV1, TRPV4 and pannexin-1 channels. Parallel data was obtained using murine acute CS-driven model systems. Finally, TRPV1/4 mRNA expression was increased in lung tissue samples from patients with COPD.Extracellular ATP is increased in the COPD affected lung and may play a key role in driving disease pathophysiology. These experiments uncover a novel mechanism which may be responsible for CS-induced ATP release. These findings highlight novel targets that could lead to the development of medicine to treat this devastating disease.
The effect of a structured technical training session on patient adherence to domiciliary non-invasive ventilation: A pre-post intervention study
Authors: Anthony Scaffardi, Swapna Mandal, Michelle Ramsay, Craig Davidson, Nicholas Hart
Journal: European Respiratory Journal (2013)

INTRODUCTION: Patient adherence to the prescription of domiciliary non-invasive ventilation (NIV) at the time of initiation is variable. The aim of this study was to investigate the effect of a structured technical training session on NIV adherence. METHODS: 70 sequential stable hypercapnic patients, naive to NIV, were recruited over an 8 month period following the addition of a structured technical training session to the standard domiciliary NIV training session. Training was delivered on the day of discharge post inpatient NIV set up and titration. Group 1 (n=40) was given conventional training by nursing staff and Group 2 (n=30) recieved a structured one hour technical training session. Ventilator adherence at 6 weeks post initiation of NIV was measured. RESULTS: In group 1, 22 patients were male with a mean age of 59 years and arterial pCO2 of 7.4kPa. Group 2 consisted of 12 male patients with a mean age of 59 years and arterial pCO2 of 8.2kPa. There was a significant increase in daily NIV use with a median adherence (IQR) of 6hrs 34mins (4hrs 51mins - 7hrs 45mins) in the group who underwent the structured technical training session compared with the conventionally trained group with an median adherence of 4hrs 44mins (1hr 31mins - 7hrs 8mins; p = 0.01) at 6 weeks CONCLUSION: In this pre-post intervention trial, a structured technical training session in addition to the nurse training session increased patient adherence to domiciliary NIV at 6 weeks
Gene therapy restores vision in a canine model of childhood blindness
Authors: Gregory M. Acland, Gustavo D. Aguirre, Jharna Ray, Qi Zhang, Tomas S. Aleman, Artur V. Cideciyan, Susan E. Pearce-Kelling, Vibha Anand, Yong Zeng, Albert M. Maguire, Samuel G. Jacobson, William W. Hauswirth, Jean Bennett
Journal: Nature Genetics (2001)
Retinoic Acid Receptor β Expression and Growth Inhibition of Gynecologic Cancer Cells by the Synthetic Retinoid N-(4-Hydroxyphenyl) Retinamide
Authors: Anita L. Sabichi, Denver T. Hendricks, Mary A. Bober, Michael J. Birrer
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The synthetic retinoid N-(4-hydroxyphenyl) retinamide (4HPR) can inhibit the growth of tumor cells. Preliminary results from a clinical trial suggest that 4HPR may reduce ovarian cancer incidence. We examined the growth-inhibitory effects of 4HPR on gynecologic cancer cell lines in vitro and the role of retinoid receptors in modulating this effect. Methods: Twelve human gynecologic cancer cell lines (the ovarian cell lines—A224, AD10, UCI 101, UCI 107, SKOV3, 222, CP70, ML3B, and ML5; the cervical cell lines—HT3 and ME180; and the endometrial cell line—Hec 1A were tested for sensitivity to 4HPR (by assaying cell proliferation rates). Gel electrophoretic analysis of DNA fragmentation was used to measure programmed cell death (apoptosis). Specific retinoid receptor (retinoic acid receptor [RAR] and retinoid X receptor) messenger RNA (mRNA) levels were measured by northern blot hybridization. AD10 cells were stably transfected with human RARβ complementary DNA, and the effect of 4HPR on cell proliferation was examined. Results: 4HPR inhibited the growth of all 12 cell lines, but to varying degrees; IC50 values (i.e., concentrations that inhibit proliferation by 50%) ranged from 0.3 to 9 µM. Following 4HPR treatment, ovarian cancer cells that were sensitive to 4HPR (222, CP70, and UCI 101; IC50 <3 µM) contained higher levels of RARβ transcripts than more resistant cells (AD10, ME180, Hec 1A, and A224; IC50 ⩾3 µM) (2.8-fold; two-sided P = .006). Anchorage-independent growth of transfected AD10 cells expressing high levels of RARβ was totally abolished, even in the absence of 4HPR; transfectants expressing low levels of RARβ exhibited lower levels of anchorage-independent growth and grew more slowly in the presence of 4HPR than control untransfected AD10 cells. Conclusion: 4HPR inhibited the proliferation of ovarian cancer cells in vitro; RARβ expression appeared to be associated with this effect.
In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination
Authors: Laura C. Bonifaz, David P. Bonnyay, Anna Charalambous, Dara I. Darguste, Shin-Ichiro Fujii, Helena Soares, Marie K. Brimnes, Bruno Moltedo, Thomas M. Moran, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2004)

The prevention and treatment of prevalent infectious diseases and tumors should benefit from improvements in the induction of antigen-specific T cell immunity. To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues. Simultaneously, we injected agonistic α-CD40 antibody to mature the dendritic cells. We found that a single low dose of antibody-conjugated ovalbumin initiated immunity from the naive CD4+ and CD8+ T cell repertoire. Unexpectedly, the αDEC-205 antigen conjugates, given s.c., targeted to dendritic cells systemically and for long periods, and ovalbumin peptide was presented on MHC class I for 2 weeks. This was associated with stronger CD8+ T cell–mediated immunity relative to other forms of antigen delivery, even when the latter was given at a thousand times higher doses. In parallel, the mice showed enhanced resistance to an established rapidly growing tumor and to viral infection at a mucosal site. By better harnessing the immunizing functions of maturing dendritic cells, antibody-mediated antigen targeting via the DEC-205 receptor increases the efficiency of vaccination for T cell immunity, including systemic and mucosal resistance in disease models.
Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience
Authors: Achim Rothe, Stephanie Sasse, Helen Goergen, Dennis A. Eichenauer, Andreas Lohri, Ulrich Jäger, Christopher Bangard, Boris Böll, Michael von Bergwelt Baildon, Sebastian Theurich, Peter Borchmann, Andreas Engert
Journal: Blood (2012)
Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat
Authors: J Santos, P-C Yang, J D Söderholm, M Benjamin, M H Perdue
Journal: Gut (2001)

BACKGROUND AND AIMS Stress may be an important factor in exacerbating inflammatory bowel disease but the underlying mechanism is unclear. Defective epithelial barrier function may allow uptake of luminal antigens that stimulate an immune/inflammatory response. Here, we examined the effect of chronic stress on colonic permeability and the participation of mast cells in this response. METHODS Mast cell deficient Ws/Ws rats and +/+ littermate controls were submitted to water avoidance stress or sham stress (one hour/day) for five days. Colonic epithelial permeability to a model macromolecular antigen, horseradish peroxidase, was measured in Ussing chambers. Epithelial and mast cell morphology was studied by light and electron microscopy. RESULTS Chronic stress significantly increased macromolecular flux and caused epithelial mitochondrial swelling in +/+ rats, but not in Ws/Ws rats, compared with non-stressed controls. Stress increased the number of mucosal mast cells and the proportion of cells showing signs of activation in +/+ rats. No mast cells or ultrastructural abnormalities of the epithelium were present in Ws/Ws rats. Increased permeability in +/+ rats persisted for 72 hours after stress cessation. CONCLUSIONS Chronic stress causes an epithelial barrier defect and epithelial mitochondrial damage, in parallel with mucosal mast cell hyperplasia and activation. The study provides further support for an important role for mast cells in stress induced colonic mucosal pathophysiology.
Isoprostanes Inhibit Vascular Endothelial Growth Factor–Induced Endothelial Cell Migration, Tube Formation, and Cardiac Vessel Sprouting In Vitro, As Well As Angiogenesis In Vivo via Activation of the Thromboxane A <sub>2</sub> Receptor
Authors: Ralf A. Benndorf, Edzard Schwedhelm, Anke Gnann, Raihana Taheri, Ghainsom Kom, Michael Didié, Anna Steenpass, Süleyman Ergün, Rainer H. Böger
Journal: Circulation Research (2008)

Isoprostanes are endogenously formed end products of lipid peroxidation. Furthermore, they are markers of oxidative stress and independent risk markers of coronary heart disease. In patients experiencing coronary heart disease, impaired angiogenesis may exacerbate insufficient blood supply of ischemic myocardium. We therefore hypothesized that isoprostanes may exert detrimental cardiovascular effects by inhibiting angiogenesis. We studied the effect of isoprostanes on vascular endothelial growth factor (VEGF)-induced migration and tube formation of human endothelial cells (ECs), and cardiac angiogenesis in vitro as well as on VEGF-induced angiogenesis in the chorioallantoic membrane assay in vivo. The isoprostanes 8-iso-PGF 2α , 8-iso-PGE 2 , and 8-iso-PGA 2 inhibited VEGF-induced migration, tube formation of ECs, and cardiac angiogenesis in vitro, as well as VEGF-induced angiogenesis in vivo via activation of the thromboxane A 2 receptor (TBXA2R): the specific TBXA2R antagonists SQ-29548, BM 567, and ICI 192,605 but not the thromboxane A 2 synthase inhibitor ozagrel blocked the effect of isoprostanes. The isoprostane 8-iso-PGA 2 degraded into 2 biologically active derivatives in vitro, which also inhibited EC tube formation via the TBXA2R. Moreover, short hairpin RNA–mediated knockdown of the TBXA2R antagonized isoprostane-induced effects. In addition, Rho kinase inhibitor Y-27632 reversed the inhibitory effect of isoprostanes and the thromboxane A 2 mimetic U-46619 on EC migration and tube formation. Finally, the various isoprostanes exerted a synergistic inhibitory effect on EC tube formation. We demonstrate for the first time that isoprostanes inhibit angiogenesis via activation of the TBXA2R. By this mechanism, isoprostanes may contribute directly to exacerbation of coronary heart disease and to capillary rarefaction in disease states of increased oxidative stress.
Culture of renal tubular cells from the urine of patients with nephropathic cystinosis.
Authors: L C Racusen, B A Fivush, H Andersson, W A Gahl
Journal: Journal of the American Society of Nephrology (1991)

Nephropathic cystinosis represents a prototype for lysosomal storage diseases and is the most common cause of renal tubular Fanconi's syndrome. Mechanisms of the tubular transport defects in this disease have not been defined, however, in part because the cells readily cultured from affected patients, leukocytes and fibroblasts, do not express epithelial transport functions. Except for a single autopsy report, renal tubular cells from these patients have not been studied in vitro. In these studies, noninvasive harvesting and culture of renal tubular cells from the urine of patients with cystinosis is described. Cultures of renal tubular cells could be established from over 50% of the isolates which contained viable cells and which remained uncontaminated in vitro. Cells had an epithelial morphology in culture, and the majority of cultured cells expressed proximal tubular brush border marker enzyme. Cultured cells also expressed the storage defect in vitro, containing cystine levels up to 100 times those of normal cells. Cultured cells could be depleted of cystine by using the thiol cysteamine. This in vitro model system should be very useful for studying the mechanisms of renal tubular transport defects in this disease.
Assessment of a Dietary Questionnaire in Cancer Patients Receiving Cytotoxic Chemotherapy
Authors: Jeffrey A. Meyerhardt, Denise Heseltine, Hannia Campos, Michelle D. Holmes, Walter C. Willett, Eric P. Winer, Peter C. Enzinger, Craig A. Bunnell, Matthew H. Kulke, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2005)

Purpose Few studies have examined the influence of diet on survival and chemotherapy-associated toxicities in patients with cancer. Although several comprehensive dietary questionnaires have been validated and calibrated in healthy populations, similar studies have not been performed among cancer patients. Methods Two hundred patients with colorectal, breast, or neuroendocrine cancer undergoing treatment with cytotoxic chemotherapy completed a self-administered, 131-item, semiquantitative food frequency questionnaire. Using the questionnaire, we calculated dietary intakes of carotenoids, tocopherols, and fatty acids, and correlated these values with relevant biomarkers measured in simultaneously collected plasma specimens. Results The Pearson correlation coefficients for various carotenoids as measured by the questionnaire, with the corresponding measurements in plasma specimens, ranged from 0.33 to 0.44 (all P &lt; .001), adjusted for total energy intake, body mass index, age, sex, smoking status, and total plasma cholesterol. Similarly, the adjusted correlation between self-reported total vitamin E intake and plasma alpha-tocopherol was 0.34 (P &lt; .001). Correlations between questionnaire and plasma measurements of trans-fat, eicosapentaenoic acid, and docosahexaenoic acid were 0.55, 0.29, and 0.42 (all P &lt; .001), respectively. These levels of correlation are consistent with those reported in similar studies of self-reported diet in otherwise healthy populations. Conclusion Among patients with cancer receiving cytotoxic chemotherapy, questionnaire-based measurements of various micronutrients and dietary factors appeared to predict meaningful differences in the corresponding measurements in plasma specimens. This dietary questionnaire could offer an informative and practical means for assessing the influence of diet in cancer patients receiving chemotherapy.
A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxaemia
Authors: I. Garcia-Talavera, M. Figueira, A. Aguirre-Jaime
Journal: Thorax (2011)

We read with great interest the recently published article by Moore et al 1 and we would like to make the following remarks.

Desaturation with exercise is still a hotly debated issue, and the papers that deal with the …
Targeted Inhibition of Farnesyltransferase in Locally Advanced Breast Cancer: A Phase I and II Trial of Tipifarnib Plus Dose-Dense Doxorubicin and Cyclophosphamide
Authors: Joseph A. Sparano, Stacy Moulder, Aslamuzzaman Kazi, Linda Vahdat, Tianhong Li, Christine Pellegrino, Pam Munster, Mokenge Malafa, David Lee, Shira Hoschander, Una Hopkins, Dawn Hershman, John J. Wright, Said M. Sebti
Journal: Journal of Clinical Oncology (2006)

Purpose To determine the recommended phase II dose (RPTD) of the farnesyltransferase (FTase) inhibitor tipifarnib when combined with doxorubicin and cyclophosphamide (AC) in patients with advanced breast cancer, the pathologic complete response (pCR) rate after preoperative treatment with four cycles of the combination in locally advanced breast cancer (LABC), and the effect of tipifarnib on primary tumor FTase enzyme activity in vivo. Patients and Methods Thirty-two patients with metastatic breast cancer (n = 11) or LABC (n = 21) received AC (doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 ) administered intravenously on day 1 plus tipifarnib (100, 200, or 300 mg bid for 6 to 14 days) without (n = 2) or with (n = 30) granulocyte colony-stimulating factor (G-CSF) for up to four cycles. Patients with LABC underwent surgery after up to four cycles of the combination. Results When combined with AC every 2 weeks plus G-CSF, the RPTD of tipifarnib was 200 mg bid administered on days 2 to 7. Seven (33%) of 21 patients (95% CI, 15% to 55%) with LABC treated with up to four cycles of the combination at the RPTD had a pCR in the breast at surgery. The five patients had serial biopsies that demonstrated at least 50% FTase enzyme inhibition in the primary tumor (median, 100%; range, 55% to 100%) after tipifarnib. Conclusion Tipifarnib may be safely combined with dose-dense AC using a dose and schedule that significantly inhibits FTase enzyme activity in human breast cancer in vivo and may enhance the pCR rate after four cycles of preoperative dose-dense AC.