tbuckley/cabot-search huggingface dataset:
Epimorphin-/- mice have increased intestinal growth, decreased susceptibility to dextran sodium sulfate colitis, and impaired spermatogenesis
Authors: Y. Wang
Journal: Journal of Clinical Investigation (2006)

Dynamic and reciprocal epithelial-mesenchymal interactions are critical for the normal morphogenesis and maintenance of epithelia. Epimorphin has been identified as a unique molecule expressed by mesenchymal cells and myofibroblasts and has putative morphogenetic effects in multiple epithelial tissues, including intestine, skin, mammary gland, lung, gallbladder, and liver. To define the in vivo role of epimorphin, we created epimorphin-null mice by targeted inactivation of the epimorphin gene. Male epimorphin-/- mice are sterile due to abnormal testicular development and impaired spermatogenesis. Intestinal growth is increased in epimorphin-/- mice due to augmented crypt cell proliferation and crypt fission during the neonatal (suckling) period, mediated at least in part by changes in bone morphogenetic protein (Bmp) and Wnt/beta-catenin signaling pathways. Colonic mucosal injury and colitis induced by dextran sodium sulfate (DSS) are ameliorated in epimorphin-/- mice, probably due to the increased proliferative capacity of the epimorphin-/- colon. These in vivo findings support the notion that epimorphin is a key stromal regulator of epithelial cell proliferation and growth in the intestine. In addition, our studies demonstrate a novel and critical role for epimorphin in regulating testicular development and growth as well as spermatogenesis.
Routine use of ancillary investigations in staging diffuse large B-cell lymphoma improves the International Prognostic Index (IPI)
Authors: Dipti Talaulikar, Bruce Shadbolt, Jane E Dahlstrom, Anne McDonald
Journal: Journal of Hematology & Oncology (2009)

The International Prognostic Index (IPI) is used to determine prognosis in diffuse large B-cell lymphoma (DLBCL). One of the determinants of IPI is the stage of disease with bone marrow involvement being classified as stage IV. For the IPI, involvement on bone marrow is traditionally defined on the basis of histology with ancillary investigations used only in difficult cases to aid histological diagnosis. This study aimed to determine the effect of the routine use of flow cytometry, immunohistochemistry and molecular studies in bone marrow staging upon the IPI.Bone marrow trephines of 156 histologically proven DLBCL cases at initial diagnosis were assessed on routine histology, and immunohistochemistry using two T-cell markers (CD45RO and CD3), two B-cell markers (CD20 and CD79a) and kappa and lambda light chains. Raw flow cytometry data on all samples were reanalysed and reinterpreted blindly. DNA extracted from archived paraffin-embedded trephine biopsy samples was used for immunoglobulin heavy chain and light chain gene rearrangement analysis. Using immunophenotyping (flow cytometry and immunohistochemistry), 30 (19.2%) cases were upstaged to stage IV. A further 8 (5.1%) cases were upstaged using molecular studies. A change in IPI was noted in 18 cases (11.5%) on immunophenotyping alone, and 22 (14.1%) cases on immunophenotyping and molecular testing. Comparison of two revised IPI models, 1) using immunophenotyping alone, and 2) using immunophenotyping with molecular studies, was performed with baseline IPI using a Cox regression model. It showed that the revised IPI model using immunophenotyping provides the best differentiation between the IPI categories.Improved bone marrow staging using flow cytometry and immunohistochemistry improves the predictive value of the IPI in patients with DLBCL and should be performed routinely in all cases.
Reproduction Rates After Cancer Treatment: Experience From the Norwegian Radium Hospital
Authors: Milada Cvancarova, Sven Ove Samuelsen, Henriette Magelssen, Sophie Dorothea Fosså
Journal: Journal of Clinical Oncology (2008)

Most studies on postcancer reproduction are limited in patient numbers and lack of control group. We have computed 10-year first postdiagnosis cumulative reproduction rates (10-PDRs) and hazard ratios (HRs) avoiding these limitations.Six thousand seventy-one patients with cancer age 15 to 45 years at diagnosis, treated from 1971 to 1997, and 30,355 controls from the general population, all born after 1950, were observed from the true (patients) or assigned (controls) date of diagnosis for a median of 10 years (range, 0 to 35). The primary focus of the study was the 10-PDR before and after 1988+ based on data from the Medical Birth Registry of Norway. Cox proportional hazards regression models were adjusted for age and calendar year at diagnosis, stratified by sex and prediagnosis parenthood.Across all cancer types, HRs of females were approximately 50% lower than those of the controls, the comparable percentage for male patients being approximately 30%, with some improvement after 1988+ for selected diagnoses. The highest 10-PDRs were observed in childless patients, with more favorable HRs in male than in female patients. In survivors with at least one child at diagnosis, the post-1988+ HRs improved significantly in patients with testicular and localized cervical cancer compared to pre-1988+ reproduction, with borderline improvement in localized ovarian cancer.Postcancer reproduction is lower than that of the general population and influenced by sex, age at diagnosis, prediagnosis parenthood, and diagnostic period with more favorable rates in males than in females. Post-1988+ fertility-saving strategies may have improved the reproduction rates for select genital cancers.
In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines
Authors: Rei Mizuno, Yuji Kamioka, Kenji Kabashima, Masamichi Imajo, Kenta Sumiyama, Eiji Nakasho, Takeshi Ito, Yoko Hamazaki, Yoshihisa Okuchi, Yoshiharu Sakai, Etsuko Kiyokawa, Michiyuki Matsuda
Journal: The Journal of Experimental Medicine (2014)

Many chemical mediators regulate neutrophil recruitment to inflammatory sites. Although the actions of each chemical mediator have been demonstrated with neutrophils in vitro, how such chemical mediators act cooperatively or counteractively in vivo remains largely unknown. Here, by in vivo two-photon excitation microscopy with transgenic mice expressing biosensors based on Förster resonance energy transfer, we time-lapse–imaged the activities of extracellular signal–regulated kinase (ERK) and protein kinase A (PKA) in neutrophils in inflamed intestinal tissue. ERK activity in neutrophils rapidly increased during spreading on the endothelial cells and showed positive correlation with the migration velocity on endothelial cells or in interstitial tissue. Meanwhile, in the neutrophils migrating in the interstitial tissue, high PKA activity correlated negatively with migration velocity. In contradiction to previous in vitro studies that showed ERK activation by prostaglandin E2 (PGE2) engagement with prostaglandin receptor EP4, intravenous administration of EP4 agonist activated PKA, inhibited ERK, and suppressed migration of neutrophils. The opposite results were obtained using nonsteroidal antiinflammatory drugs (NSAIDs). Therefore, NSAID-induced enteritis may be caused at least partially by the inhibition of EP4 receptor signaling of neutrophils. Our results demonstrate that ERK positively regulates the neutrophil recruitment cascade by promoting adhesion and migration steps.
Is Metformin Safe in Patients With Mild Renal Insufficiency?
Authors: Amir Kazory, Katherine Walsh, Eloise Harman, Zvi Talor
Journal: Diabetes Care (2007)

Among the first million patients who received metformin in the U.S., 47 patients developed metformin-associated lactic acidosis (MALA), with 43 having predisposing factors for lactic acidosis (including moderate to severe renal failure and congestive heart failure) (1). Although there was initial concern, studies have suggested that MALA is secondary to underlying conditions and represents a coincidental finding (2,3). While the current consensus is that the risk of lactic acidosis is negligible when …
CD44 on LS174T Colon Carcinoma Cells Possesses E-Selectin Ligand Activity
Authors: William D. Hanley, Monica M. Burdick, Konstantinos Konstantopoulos, Robert Sackstein
Journal: Cancer Research (2005)

Abstract Metastasis of circulating tumor cells requires a multistep cascade of events initiated by adhesion of tumor cells to the vascular endothelium of involved tissues. This process occurs under the forces of blood flow and is promoted by adhesion molecules specialized to interact under shear conditions. The endothelial molecule E-selectin is a major mediator of these adhesive events, and there is strong evidence that E-selectin receptor-ligand interactions contribute to the formation of metastasis. However, little is known about the identity of E-selectin ligand(s) expressed on cancer cells. To address this issue, we did SDS-PAGE analysis of membrane proteins, metabolic inhibition studies, and blot rolling assays of LS174T, a colon carcinoma cell line known to interact with E-selectin under physiologic flow conditions. Our studies show that LS174T cells express the hematopoietic cell E/L-selectin (HCELL) glycoform of CD44, which functions as a high-affinity E-selectin glycoprotein ligand on these cells. However, in contrast to the HCELL glycoform on human hematopoietic progenitor cells, which expresses carbohydrate-binding determinant(s) for E-selectin primarily on N-glycans of standard CD44, the relevant determinant(s) on LS174T cells is expressed on O-glycans and is predominantly found on variant isoforms of CD44 (CD44v). Our finding that tumor-associated CD44 splice variant(s) express E-selectin ligand activity provides novel perspectives on the biology of CD44 in cancer metastasis.
Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women
Authors: Evelyne M Dewulf, Patrice D Cani, Sandrine P Claus, Susana Fuentes, Philippe GB Puylaert, Audrey M Neyrinck, Laure B Bindels, Willem M de Vos, Glenn R Gibson, Jean-Paul Thissen, Nathalie M Delzenne
Journal: Gut (2012)

<h3>Objective</h3> To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women. <h3>Methods</h3> A double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood, faeces and urine sampling, oral glucose tolerance test, homeostasis model assessment and impedancemetry were performed before and after treatment. The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by <sup>1</sup>H-NMR spectroscopy. <h3>Results</h3> Treatment with ITF prebiotics, but not the placebo, led to an increase in <i>Bifidobacterium</i> and <i>Faecalibacterium prausnitzii</i>; both bacteria negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also decreased <i>Bacteroides intestinalis</i>, <i>Bacteroides vulgatus</i> and <i>Propionibacterium</i>, an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels. No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses. However, ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and/or diabetes. <h3>Conclusions</h3> ITF prebiotics selectively changed the gut microbiota composition in obese women, leading to modest changes in host metabolism, as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures.
High-content cytometry and transcriptomic biomarker profiling of human B-cell activation
Authors: Christian Hennig, Claudia Ilginus, Kaan Boztug, Julia Skokowa, Laszlo Marodi, Anna Szaflarska, Mareike Sass, Claudio Pignata, Sara Sebnem Kilic, Isabel Caragol, Ulrich Baumann, Christoph Klein, Karl Welte, Gesine Hansen
Journal: Journal of Allergy and Clinical Immunology (2013)
Oesophageal tone in patients with achalasia
Authors: M González, F Mearin, C Vasconez, J-R Armengol, J-R Malagelada
Journal: Gut (1997)

The diagnosis and classification of oesophageal motility disorders is currently based on assessment of the phasic contractile activity of the oesophagus. Tonic muscular contraction of the oesophageal body (oesophageal tone) has not been well characterised.To quantify oesophageal tonic activity in healthy subjects and in patients with achalasia.Oesophageal tone was measured in 14 patients with untreated achalasia and in 14 healthy subjects. In eight patients with achalasia, oesophageal tone was again measured one month after either endoscopic or surgical treatment.Tonic wall activity was quantified by means of a flaccid intraoesophageal bag, 5 cm long and of 120 ml maximal capacity, which was placed and maintained 5 cm above the lower oesophageal sphincter and connected to an external electronic barostat. The experimental design included measurement of oesophageal basal tone and compliance as well as the oesophageal tone response to a nitric oxide donor (0.5 ml amyl nitrite inhalation).Oesophageal basal tone, expressed as the intrabag (intraoesophageal) volume at a minimal distending pressure (2 mm Hg), did not differ significantly between patients with achalasia and healthy controls (6.6 (2.5) ml versus 4.1 (0.8) ml, respectively). Oesophageal compliance (volume/pressure relation during intraoesophageal distension) was significantly increased in achalasia (oesophageal extension ratio: 3.2 (0.4) ml/mm Hg versus 1.9 (0.2) ml/mm Hg; p < 0.01). Amyl nitrite inhalation induced oesophageal relaxation both in patients and in controls, but the magnitude of relaxation was greater in the latter (intrabag volume increase: 15.3 (2.4) ml versus 36.2 (7.1) ml; p < 0.01).In patients with achalasia, oesophageal tonic activity, and not only phasic activity, is impaired. Although oesophageal compliance is increased, residual oesophageal tone is maintained so that a significant relaxant response may occur after pharmacological stimulation.
The Kidney Disease Screening and Awareness Program (KDSAP)
Authors: Li-Li Hsiao, Jingshing Wu, Albert C. Yeh, Eric C. Shieh, Cheryl Cui, Ang Li, Laura C. Polding, Rayhnuma Ahmed, Kenneth Lim, Tzong-Shi Lu, Connie M. Rhee, Joseph V. Bonventre
Journal: Journal of the American Society of Nephrology (2014)

Despite the increasing prevalence of CKD in the United States, there is a declining interest among United States medical graduates in nephrology as a career choice. Effective programs are needed to generate interest at early educational stages when career choices can be influenced. The Kidney Disease Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard College that increases student knowledge of and interest in kidney health and disease, interest in nephrology career paths, and participation in kidney disease research. This model, built on physician mentoring, kidney screening of underserved populations, direct interactions with kidney patients, and opportunities to participate in kidney research, can be reproduced and translated to other workforce-challenged subspecialties.
Factors associated with elevated exhaled nitric oxide fraction in infants with recurrent respiratory symptoms
Authors: Anne Kotaniemi-Syrjänen, L. Pekka Malmberg, Kristiina Malmström, Anna S. Pelkonen, Mika J. Mäkelä
Journal: European Respiratory Journal (2012)

Exhaled nitric oxide fraction (F(eNO)) has been proposed as a noninvasive marker of eosinophilic bronchial inflammation in active asthma, and supposed to reflect responsiveness to corticosteroid therapy. There are several factors influencing F(eNO), and its role in early childhood respiratory disorders needs to be established. Between 2004 and 2008, 444 children aged <3 yrs with recurrent lower respiratory tract symptoms were referred to a tertiary centre for further investigation. 136 full-term, steroid-free, infection-free infants, median age of 16.4 months (range 4.0-26.7 months), successfully underwent measurement of F(eNO), lung function tests, and a dosimetric methacholine challenge test. The median level of F(eNO) was 19.3 ppb (interquartile range 12.3-26.9 ppb). Elevated F(eNO) (≥ 27 ppb, the highest quartile) was associated with maternal history of asthma (adjusted OR 3.2, 95% CI 1.3-8.1; p=0.012), and increased airway responsiveness (the provocative dose of methacholine causing a 40% fall in maximal expiratory flow at functional residual capacity ≤ 0.30 mg) (adjusted OR 4.1, 95% CI 1.4-12.7; p=0.012). Atopy, blood eosinophilia and lung function were not associated with elevated F(eNO). In conclusion, maternal history of asthma, and increased airway responsiveness are associated with elevated F(eNO) in infants with recurrent lower respiratory tract symptoms.
A pragmatic randomised controlled trial of local corticosteroid injection and physiotherapy for the treatment of new episodes of unilateral shoulder pain in primary care
Authors: E M Hay
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> To compare the long term effectiveness of local steroid injections administered by general practitioners with practice based physiotherapy for treating patients presenting in primary care with new episodes of unilateral shoulder pain. <b>Methods:</b> Adults consulting with shoulder pain were recruited by their general practitioner. Patients were randomly allocated to receive either corticosteroid injections or community based physiotherapy. Primary outcome was self reported disability from shoulder problems at six months. Secondary outcomes included participant's global assessment of change; pain; function; "main complaint"; range of shoulder movement; co-interventions. A study nurse unaware of the treatment allocation performed baseline and follow up assessments. Analysis was by intention to treat. <b>Results:</b> Over 22 months 207 participants were randomised, 103 to physiotherapy and 104 to injection. Prognostic variables were similar between the two groups at baseline. Mean (SD) improvements in disability scores at six weeks were 2.56 (5.4) for physiotherapy and 3.03 (6.3) for injection (mean difference=−0.5, 95% confidence interval (95% CI): −2.1 to 1.2) and at six months were 5.97 (5.4) for physiotherapy and 4.55 (5.9) for injection (mean difference=1.4, 95% CI −0.2 to 3.0). A "successful outcome" (a minimum 50% drop in the disability score from baseline) at six months was achieved by 59/99 (60%) in the physiotherapy group and 51/97 (53%) in the injection group (percentage difference=7%, 95% CI −6.8% to 20.4%). Co-interventions were more common in the injection group during follow up. <b>Conclusion:</b> Community physiotherapy and local steroid injections were of similar effectiveness for treating new episodes of unilateral shoulder pain in primary care, but those receiving physiotherapy had fewer co-interventions.
P277 The Incidence Of Lung Cancer In People With Idiopathic Pulmonary Fibrosis And Connective Tissue Disease Associated Pulmonary Fibrosis In The Uk: A Population Based Study
Authors: W. Dalleywater, H. Powell, G. Jones, R. Hubbard, V. Navaratnam
Journal: Thorax (2014)

<h3>Introduction</h3> Studies have suggested that lung cancer is more common in people with idiopathic pulmonary fibrosis (IPF). However, there is limited information on the risk of lung cancer in individuals with connective tissue disease associated pulmonary fibrosis (CTD-PF). The aim of this study was to compare the incidence of lung cancer in people with IPF and CTD-PF with that of the general population. <h3>Methods</h3> Using electronic primary care records from The Health Improvement Network (THIN), we identified incident cases of IPF and CTD-PF between 2000 and 2011. For every case of IPF or CTD-PF, up to 4 general population controls matched on age, sex and general practice were randomly selected. We conducted a matched cohort analysis to estimate rate ratios for lung cancer in cases of IPF and CTD-PF compared with matched controls, adjusting for smoking habit. <h3>Results</h3> Our study population consisted of 3266 incident cases of IPF, 494 cases of CTD-PF and 14,463 matched general population controls. The majority (64.1%) of people with IPF were male, while most (55.3%) of those with CTD-PF were female. Individuals with CTD-PF were also younger at time of diagnosis compared to people with IPF (mean age at diagnosis 69.0 vs. 74.2 years; p &lt; 0.001). The median follow up time for our study population was 3.1 years (Interquartile range [IQR] 1.3 to 5.6). During this time 80 (2.5%) individuals with IPF, 9 (1.8%) with CTD-PF and 149 (1.0%) controls were diagnosed with lung cancer. After adjusting for smoking and the matching factors, the incidence of lung cancer was higher in people with IPF (Rate Ratio [RR] 3.61, 95% Confidence Interval [CI] 2.44 to 5.34) and CTD-PF (RR 2.35, 95% CI 0.78 to 7.09; p value for trend=0.013) compared to the controls (see Figure 1). <h3>Conclusion</h3> Individuals with IPF and CTD-PF are at an increased risk of lung cancer, which cannot be fully explained by smoking habit. With the increasing use of new therapies that may prolong the median survival in individuals with lung fibrosis, our findings raise the possibility these patients may represent a suitable population for lung cancer screening.
The role of erlotinib in advanced NSCLC
Authors: N Goldsack
Journal: Thorax (2005)

▴ Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al . Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med2005;353:123–32 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] ▴ Tsao M-S, Sakurada A, Cutz JC, et al . Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Engl J Med2005;353:133–44 [OpenUrl][5][CrossRef][6][PubMed][7][Web of Science][8] Relapsed advanced non-small cell lung cancer (NSCLC) carries a dismal prognosis and new treatments are particularly welcome. These papers evaluate the use of erlotinib, a tyrosine kinase inhibitor of the epidermal … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DShepherd%26rft.auinit1%253DF.%2BA.%26rft.volume%253D353%26rft.issue%253D2%26rft.spage%253D123%26rft.epage%253D132%26rft.atitle%253DErlotinib%2Bin%2BPreviously%2BTreated%2BNon-Small-Cell%2BLung%2BCancer%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa050753%26rft_id%253Dinfo%253Apmid%252F16014882%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/external-ref?access_num=10.1056/NEJMoa050753&link_type=DOI [3]: /lookup/external-ref?access_num=16014882&link_type=MED&atom=%2Fthoraxjnl%2F60%2F11%2F931.atom [4]: /lookup/external-ref?access_num=000230438800004&link_type=ISI [5]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DTsao%26rft.auinit1%253DM.%2BS.%26rft.volume%253D353%26rft.issue%253D2%26rft.spage%253D133%26rft.epage%253D144%26rft.atitle%253DErlotinib%2Bin%2BLung%2BCancer%2B--%2BMolecular%2Band%2BClinical%2BPredictors%2Bof%2BOutcome%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa050736%26rft_id%253Dinfo%253Apmid%252F16014883%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 [6]: /lookup/external-ref?access_num=10.1056/NEJMoa050736&link_type=DOI [7]: /lookup/external-ref?access_num=16014883&link_type=MED&atom=%2Fthoraxjnl%2F60%2F11%2F931.atom [8]: /lookup/external-ref?access_num=000230438800005&link_type=ISI