tbuckley/cabot-search huggingface dataset:
Effects of streptozotocin diabetes in the rat on blood levels of ten specific plasma proteins and on their net biosynthesis by the isolated perfused liver
Authors: Leon L. Miller, Donna Eddy Treat, Bruce Fridd, Drusilla Wemett
Journal: Hepatology (1990)

Adult male Sprague-Dawley rats with streptozotocin-induced diabetes (6 to 8 wk duration), treated or untreated with insulin, were studied with two aims: (a) to ascertain whether protracted diabetes in the rat is associated with changes in circulating plasma protein levels analogous to those reported in human diabetic patients with clinical evidence of complications; (b) to evaluate the effects of experimental diabetes on the net cumulative biosynthesis of 10 specific plasma proteins by the isolated liver, perfused for 24 hr. Samples of liver donor plasma and samples of perfusate were analyzed by single radial immunodiffusion or by rocket immunoelectrophoresis for albumin, α1-macroglobulin and the acute phase glycoproteins: fibrinogen, α1-acid glycoprotein (Darcy), α1, acid glycoprotein (Kawasaki), haptoglobin, α2-(acute phase) globulin, hemopexin, C3-complement and ceruloplasmin. Diabetes (6 to 8 wk), untreated with insulin, resulted in significantly increased liver donor plasma levels of α1-acid glycoprotein (Darcy) and α1-acid glycoprotein (Kawasaki); plasma levels of hemopexin and of C3 decreased to 75% and 30% of normal, respectively. Insulin treatment of diabetic liver donors for 6 to 8 wk prevented the increase in α1-acid glycoprotein (Darcy) and α1-acid glycoprotein (Kawasaki) and minimized the decrease in C3 to 75% of normal. Perfused livers from untreated diabetic rats (6 to 8 wk) showed slightly decreased cumulative synthesis and secretion of α1-acid glycoprotein (Darcy); however, synthesis of albumin was reduced to 35% of normal and that of eight glycoproteins ranged from 25% of normal and that of eight glycoproteins renged from 25% of normal (fibrinogen) to 12% of normal (C3). The striking in vitro induction of increased synthesis of acute-phase proteins by cortisol plus insulin in the isolated perfused normalliver was in contrast to the severely attenuated induction in perfused livers of untreated diabetic rats, which ranges from 50% of normal for α1-acid glycoprotein (Darcy) to 5% of normal (C3). Severely negative perfusate nitrogen balance and impaired glucose utilization by perfused untreated diabetic livers contrasted with positive nitrogen balance and good glucose utilization of normal livers in response to insulin plus cortisol. The plasma protein synthetic capacity and the in vitro response to insulin plus cortisol of perfused livers from insulin-treated diabetic rats were normal for seven of the proteins but moderately decreased for albumin, haptoglobin and C3.(HEPATOLOGY 1990; 11:635-645.)
Development of an Illumina-based ChIP-exonuclease method provides insight into FoxA1-DNA binding properties
Authors: Aurelien A Serandour, Gordon D Brown, Joshua D Cohen, Jason S Carroll
Journal: Genome biology (2013)

ChIP-exonuclease (ChIP-exo) is a modified ChIP-seq approach for high resolution mapping of transcription factor DNA sites. We describe an Illumina-based ChIP-exo method which provides a global improvement of the data quality of estrogen receptor (ER) ChIP and insights into the motif structure for key ER-associated factors. ChIP-exo of the ER pioneer factor FoxA1 identifies protected DNA with a predictable 8 bp overhang from the Forkhead motif, which we term mesas. We show that mesas occur in multiple cellular contexts and exist as single or overlapping motifs. Our Illumina-based ChIP-exo provides high resolution mapping of transcription factor binding sites.
Intraluminal Stenting in the Management of Adhesional Intestinal Obstruction
Authors: D J Defriend, O E Klimack, C S Humphrey, I G Schraibman
Journal: Journal of the Royal Society of Medicine (1997)

Intraluminal stenting of the small bowel has been advocated as a method of reducing the risk of recurrent adhesional obstruction in patients requiring adhesolysis. We reviewed the complications and efficacy of this technique in 25 patients undergoing surgery for relief of intestinal obstruction due to complex, extensive and dense adhesions. Five patients developed minor and three patients major complications. Three (13%) of 23 patients alive after mean follow-up of 4 years had had episodes of recurrent intestinal obstruction, but none had required reoperation. Intraluminal stenting remains of unproven efficacy. It may find a place as an adjunct to adhesolysis in patients requiring repeated operations for the relief of obstruction due to extensive and dense adhesions; but, in view of the high rate of complications, careful case selection will be necessary.
Role of the Chemokine Receptors CXCR3 and CCR4 in Human Pulmonary Fibrosis
Authors: Patrizia Pignatti, Giuseppe Brunetti, Dania Moretto, Mona-Rita Yacoub, Marco Fiori, Bruno Balbi, Antonella Balestrino, Gabriella Cervio, Stefano Nava, Gianna Moscato
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis.To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF).We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects.We evaluated the expression of CXCR3 and CCR4 in blood and bronchoalveolar lavage (BAL) T lymphocytes by flow cytometry and the chemokine CXCL10, CXCL11 and CCL17 BAL concentration by singular immunoassay.Patients with IPF had a significantly lower CXCR3 and a higher CCR4 expression on BAL CD4 T cells compared with the other groups. Among patients with IPF, those treated with corticosteroids exhibited higher CXCR3 and lower CCR4 expression compared with untreated patients. CXCR3 expression correlated with BAL lymphocytes and CCR4 with BAL neutrophils and eosinophils. CXCL10 levels correlated with the expression of CXCR3 on BAL CD4 cells. CXCL11 was undetectable in almost all patients, whereas CCL17 was primarily detectable in patients with IPF. The percentage of BAL CCR4CD4 cells negatively correlated with DL(CO). The changes in the total lung capacity, VC, and of the alveolar-arterial PO2 gradient in patients with IPF and those with nIPF 6 to 12 mo after the first evaluation were associated with CD4CXCR3 percentage on BAL cells.We found an imbalance in CXCR3/CCR4 expression on BAL CD4 lymphocytes and reduced CXCL10 BAL levels in patients with IPF, suggesting a pivotal role of these molecules in IPF.
Repression of chimeric transcripts emanating from endogenous retrotransposons by a sequence-specific transcription factor
Authors: Ka Sin Mak, Jon Burdach, Laura J Norton, Richard CM Pearson, Merlin Crossley, Alister PW Funnell
Journal: Genome biology (2014)

Retroviral elements are pervasively transcribed and dynamically regulated during development. While multiple histone- and DNA-modifying enzymes have broadly been associated with their global silencing, little is known about how the many diverse retroviral families are each selectively recognized.Here we show that the zinc finger protein Krüppel-like Factor 3 (KLF3) specifically silences transcription from the ORR1A0 long terminal repeat in murine fetal and adult erythroid cells. In the absence of KLF3, we detect widespread transcription from ORR1A0 elements driven by the master erythroid regulator KLF1. In several instances these aberrant transcripts are spliced to downstream genic exons. One such chimeric transcript produces a novel, dominant negative isoform of PU.1 that can induce erythroid differentiation.We propose that KLF3 ensures the integrity of the murine erythroid transcriptome through the selective repression of a particular retroelement and is likely one of multiple sequence-specific factors that cooperate to achieve global silencing.
The Nasal Allergen Challenge Protocol of the Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC): Validation in a Clinical Trial of Cat Synthetic Peptide Immunoregulatory Epitopes (Cat-SPIRE)
Authors: Helen Neighbour, Mark Larché, Lisa Steacy, Kristen Armstrong, Pascal L.C. Hickey, Mena Soliman, Anne Ellis
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract IA18: A genomics approach to discover small-molecule perturbagens of cancer cells
Authors: Kimberly Stegmaier
Journal: Cancer Research (2012)

Abstract Aberrantly activated transcription factors and/or transcriptional programs play a critical role in the development of most cancers. In some cancers, the oncogenic transcription factors have been well characterized and result from either the ectopic activity of native transcription factors or from a chromosomal translocations driving overexpression or producing a mutant transcription factor. In other cases, the direct causative event of the aberrant transcriptional signature is unknown. Given their central role in cancer development, directly targeting transcription factors should be a propitious anti-tumor strategy. However, with the exception of the nuclear hormone receptor family of transcription factors, transcription factor oncoproteins have been largely refractory to conventional drug discovery approaches. While there have been advances in our ability to assess gene expression changes on a global scale, almost all existing approaches (e.g., microarrays, next generation sequencing) cannot be applied to large-scale screening endeavors due to cost and throughput limitations. Alternatively, the use of reporter systems and phenotypic endpoints (e.g., viability) has been challenged by false-positives. Recognizing these shortcomings, we developed an assay approach that allows interrogation of complex gene expression signatures in high-throughput format. Gene Expression-based High-throughput Screening (GE-HTS) allows for the assessment of expression of hundreds of endogenous genes in 384-well format, overcoming some of the challenges that are inherent in conventional target- and phenotype-based screening. We have used GE-HTS in small-molecule library screening endeavors to identify compounds that induce differentiation signatures in different cancer types in the absence of a known target, as well as alter the transcriptional activity of aberrant, oncogenic transcription factors. These compounds have served as leads for clinical trial development as well as tool compounds to further dissect biological mechanisms of disease pathogenesis. Citation Format: Kimberly Stegmaier. A genomics approach to discover small-molecule perturbagens of cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr IA18.
Effects of Interleukin-2 Treatment on CD1d-Restricted Natural Killer T Cells
Authors: Hans van der Vliet, Henry Koon, Mark Exley
Journal: Clinical Cancer Research (2007)

In Response: We thank our colleagues for their letter and discussion. Sandberg and Moll note that interleukin-2 (IL-2) combined with highly active antiretroviral therapy (HAART) administered over 1 year for human immunodeficiency virus infection results in increased iNKT cells (1) and suggest that a similar effect might occur with high-dose IL-2 for cancer. They propose that although chronic infection with human immunodeficiency virus and IL-2 dosage may contribute to the different effects on iNKT levels, their later follow-up is “the most likely explanation…” There are several difficulties in comparing the two studies. We suspect the first two differences they cite as contributing are key. Chronic infection with human immunodeficiency virus is known through their work as well as ours and others to rapidly deplete iNKT (2–4), partly although not completely explained by direct infection of CD4+ iNKT (3–5) and lower IL-2 dosage over a longer period for human immunodeficiency virus (>10-fold higher dose for cancer, also known to produce much more severe side effects). Furthermore, in their human immunodeficiency virus study, the patients receiving IL-2 also received HAART and we have shown that antiretroviral therapy increases iNKT levels (6). This was also seen in the Moll study (1), but the addition of IL-2 resulted in higher iNKT levels. Examination of the effects of long-term use of low-dose IL-2 alone in this setting would be informative. Interruptions in HAART have been tried in the context of other trials. Therefore, although we agree that follow-up time may contribute to different observations, differences in disease, other medications, and dosage are major factors.As they point out, one could speculate that the transient change in circulating iNKT levels may have deleterious consequences. We noted a relative increase in DN iNKT after the 1st week of HD IL-2, which would not be expected to be detrimental for cancer patients. Additionally, we observed an increase in the total number of iNKT before the second HD IL-2 administration and actually a nonsignificant decrease after the first administration. The latter might reflect a higher responsiveness of conventional T cells to IL-2 (compared with iNKT) that would be reflected as a decrease in the iNKT percentage of total lymphocytes.We agree that data from longer-term follow-up would be informative. However, in this patient population, a significant number of patients have progressed by even 6 to 8 weeks and are receiving other treatment modalities that may affect their lymphocyte subsets. Long-term follow-up is unfortunately not practical for most patients given high-dose IL-2. We did look at 2 months posttreatment in limited numbers of evaluable patients and did not observe an increase in iNKT percentage compared with baseline.
Effect of adherence to European treatment recommendations on early arthritis outcome: data from the ESPOIR cohort
Authors: Cécile Escalas, Marie Dalichampt, Bernard Combe, Bruno Fautrel, Francis Guillemin, Pierre Durieux, Maxime Dougados, Philippe Ravaud
Journal: Annals of the Rheumatic Diseases (2012)

Objective To assess the association of adherence to the 2007 recommendations of the European League Against Rheumatism (EULAR) for managing early arthritis and radiographic progression and disability in patients Methods The authors conducted a prospective population-based cohort study. The ESPOIR cohort was a French cohort of 813 patients with early arthritis not receiving disease-modifying antirheumatic drugs (DMARDs). Adherence to the 2007 EULAR recommendations was defined by measuring adherence to three of the recommendations concerning the initiation and early adjustment of DMARDs. The study endpoints were radiographic progression, defined as the presence of at least one new erosion between baseline and 1 year, and disability as a heath assessment questionnaire score ≥1 at 2 years. A propensity score of being treated according to the recommendations was developed. Results After adjustment for propensity score, treatment centre and the main confounding factors, patients without recommendation adherence were at increased risk of radiographic progression at 1 year, and of functional impairment at 2 years (OR 1.98, (95% CI: 1.08 to 3.62 and OR: 2.36, (95% CI: 1.17 to 4.67), respectively). Conclusions Early arthritis patients whose treatment adhered to the 2007 EULAR recommendations seemed to benefit from such treatment in terms of risk of clinical and radiographic progression. Using a propensity score of being treated according to recommendations in observational studies may be useful in assessing the potential impact of these recommendations on outcome.
Limited Amounts of Dendritic Cells Migrate into the T-Cell Area of Lymph Nodes but Have High Immune Activating Potential in Melanoma Patients
Authors: Pauline Verdijk, Erik H.J.G. Aarntzen, W. Joost Lesterhuis, A.C. Inge Boullart, Ellemieke Kok, Michelle M. van Rossum, Simon Strijk, Femke Eijckeler, Johannes J. Bonenkamp, Joannes F.M. Jacobs, Willeke Blokx, J. Han J.M. vanKrieken, Irma Joosten, Otto C. Boerman, Wim J.G. Oyen, Gosse Adema, Cornelis J.A. Punt, Carl G. Figdor, I. Jolanda M. de Vries
Journal: Clinical Cancer Research (2009)

The success of immunotherapy with dendritic cells (DC) to treat cancer is dependent on effective migration to the lymph nodes and subsequent activation of antigen-specific T cells. In this study, we investigated the fate of DC after intradermal (i.d.) or intranodal (i.n.) administration and the consequences for the immune activating potential of DC vaccines in melanoma patients.DC were i.d. or i.n. administered to 25 patients with metastatic melanoma scheduled for regional lymph node resection. To track DC in vivo with scintigraphic imaging and in lymph nodes by immunohistochemistry, cells were labeled with both [(111)In]-indium and superparamagnetic iron oxide.After i.d. injection, maximally 4% of the DC reached the draining lymph nodes. When correctly delivered, all DC were delivered to one or more lymph nodes after i.n. injection. Independent of the route of administration, large numbers of DC remained at the injection site, lost viability, and were cleared by infiltrating CD163+ macrophages within 48 hours. Interestingly, 87 +/- 10% of the surviving DC preferentially migrated into the T-cell areas, where they induced antigen-specific T-cell responses. Even though more DC reached the T-cell areas, i.n. injection of DC induced similar antigen-specific immune responses as i.d. injection. Immune responses were already induced with <5 x 10(5) DC migrating into the T-cell areas.Monocyte-derived DC have high immune activating potential irrespective of the route of vaccination. Limited numbers of DC in the draining lymph nodes are sufficient to induce antigen-specific immunologic responses.
TGFβ Triggers miR-143/145 Transfer From Smooth Muscle Cells to Endothelial Cells, Thereby Modulating Vessel Stabilization
Authors: Montserrat Climent, Manuela Quintavalle, Michele Miragoli, Ju Chen, Gianluigi Condorelli, Leonardo Elia
Journal: Circulation Research (2015)

Rationale: The miR-143/145 cluster is highly expressed in smooth muscle cells (SMCs), where it regulates phenotypic switch and vascular homeostasis. Whether it plays a role in neighboring endothelial cells (ECs) is still unknown. Objective: To determine whether SMCs control EC functions through passage of miR-143 and miR-145. Methods and Results: We used cocultures of SMCs and ECs under different conditions, as well as intact vessels to assess the transfer of miR-143 and miR-145 from one cell type to another. Imaging of cocultured cells transduced with fluorescent miRNAs suggested that miRNA transfer involves membrane protrusions known as tunneling nanotubes. Furthermore, we show that miRNA passage is modulated by the transforming growth factor (TGF) β pathway because both a specific transforming growth factor-β (TGFβ) inhibitor (SB431542) and an shRNA against TGFβRII suppressed the passage of miR-143/145 from SMCs to ECs. Moreover, miR-143 and miR-145 modulated angiogenesis by reducing the proliferation index of ECs and their capacity to form vessel-like structures when cultured on matrigel. We also identified hexokinase II ( HKII ) and integrin β 8 ( ITGβ8 )—2 genes essential for the angiogenic potential of ECs—as targets of miR-143 and miR-145, respectively. The inhibition of these genes modulated EC phenotype, similarly to miR-143 and miR-145 overexpression in ECs. These findings were confirmed by ex vivo and in vivo approaches, in which it was shown that TGFβ and vessel stress, respectively, triggered miR-143/145 transfer from SMCs to ECs. Conclusions: Our results demonstrate that miR-143 and miR-145 act as communication molecules between SMCs and ECs to modulate the angiogenic and vessel stabilization properties of ECs.
Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status
Authors: Sarah F. Marshall, Leslie Bernstein, Hoda Anton-Culver, Dennis Deapen, Pamela L. Horn-Ross, Harvey Mohrenweiser, David Peel, Rich Pinder, David M. Purdie, Peggy Reynolds, Dan Stram, Dee West, William E. Wright, Argyrios Ziogas, Ronald K. Ross
Journal: JNCI Journal of the National Cancer Institute (2005)

Epidemiologic studies of the association between nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and breast cancer risk have yielded inconsistent results. We investigated the association of NSAID use with risk of breast cancer in the California Teachers Study cohort, with special attention to risk of specific breast cancer subtypes and to type of NSAID used.We analyzed data on 114 460 women in the California Teachers Study cohort who were aged 22 to 85 years and free of breast cancer at baseline in 1995 to 1996. Information on frequency and duration of NSAID use was collected through a self-administered questionnaire. A total of 2391 women were diagnosed with breast cancer during the follow-up period from 1995 to 2001. We used Cox proportional hazards regression to estimate relative risks (RR) and 95% confidence intervals (CI) of breast cancer subtypes with NSAID use.Neither regular use (more than once a week) of any NSAID (aspirin and ibuprofen combined) nor regular use of aspirin was associated with breast cancer risk (RR = 1.09, 95% CI = 0.97 to 1.21 for daily versus no regular use of NSAIDs and RR = 0.98, 95% CI = 0.86 to 1.13 for daily versus no regular use of aspirin). However, long-term (> or = 5 years) daily aspirin users had a non-statistically significant decreased risk of estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer (RR = 0.80, 95% CI = 0.62 to 1.03). In contrast, we observed a statistically significantly increased risk of ER/PR-negative breast cancer with long-term daily use of aspirin (RR = 1.81, 95% CI = 1.12 to 2.92). In this population, 11 fewer ER/PR-positive breast cancer cases and seven excess ER/PR-negative breast cancer cases may be due to daily long-term aspirin use among 2391 breast cancer cases observed over 6 years if the association were proven to be causal. Long-term daily use of ibuprofen was also associated with an increased risk of breast cancer (RR = 1.51, 95% CI = 1.17 to 1.95), particularly of nonlocalized tumors (RR = 1.92, 95% CI = 1.24 to 2.97). If causality were subsequently proven, 16 of the observed 2391 breast cancer cases and 8 of the 713 non-localized breast cancer cases would be attributable to long-term daily use of ibuprofen.Long-term daily use of NSAIDs was not associated with breast cancer risk overall. Ibuprofen use was associated with an increased risk of breast cancer, and long-term daily aspirin use was associated with an increased risk of ER/PR-negative breast cancer. However, it is not clear if the observed association is causal.