tbuckley/cabot-search huggingface dataset:
PMO-238 Blockade of the B7 integrin prevents adherence of t lymphocytes to MAdCAM-1 in an in vitro model of vascular microcirculation post-capillary shear flow
Authors: C A Lamb, G O'Boyle, D E Jones, J C Mansfield, J A Kirby
Journal: Gut (2012)

<h3>Introduction</h3> The intestinal vascular microcirculation plays a pivotal role in the immune cell dysregulation that drives inflammatory bowel disease. T lymphocyte recruitment, adherence and migration are dependent on the integrin heterodimer α4β7, which binds with high affinity to vascular endothelium expressing MAdCAM-1, prior to lymphocyte diapedesis into the lamina propria. This integrin therefore provides a potential therapeutic target. <h3>Methods</h3> Using Cellix<sup>®</sup> technology, a dynamic in vitro model was created, testing the potential of β7 integrin blockade to impair lymphocyte adhesion to MAdCAM-1 under shear flow. The Cellix<sup>®</sup> system comprises a microfluidic platform and nano pump, with biochip channels that replicate the shear flow and stress found in post-capillary venules. Peripheral blood mononuclear cells (PBMC) were utilised, along with HuT78 T cells that constitutively express the α4β7 integrin and the chemokine receptor CXCR4, known to be upregulated in inflammatory bowel disease. Biochips were coated for 12 h at 4°C with 10 μg/ml MAdCAM-1 Fc, then blocked with 0.1% BSA for 30 min to prevent non-specific adherence to plastic. Adherence of T cells was quantitatively assessed by microscopy at a physiological flow rate of 1 dyne/cm<sup>3</sup>. The effect of an anti-human β7 integrin monoclonal antibody (clone Fib504, BD Pharmingen) on lymphocyte adherence was measured. 3 nM of the chemokine CXCL12 (ligand for CXCR4) was added to the system to model the pro-inflammatory environment present in inflammatory bowel disease. Experiments were performed at 37°C. <h3>Results</h3> HuT78 lymphocytes and PBMC (5×10<sup>6</sup>/ml) provided consistent adherence to MAdCAM-1 under flow, mean ± SE adherent cells/hpf of 32.8±4.5 and 46.2±3 respectively. Adherence was significantly improved with the addition of 3 nM CXCL12 to 45.7±2.8 (p&lt;0.05) and 78.5±1.5 (p&lt;0.001). Incubating the cells with the Fib504 anti-β7 integrin antibody, led to a significant reduction in adherence of unstimulated cells to 17.8±2 (p&lt;0.001) and 18±3.2 (p&lt;0.0001). This reduction was maintained on stimulation with CXCL12, at 17.3±0.9 (p&lt;0.001), and 5.3±0.9 (p&lt;0.0001). <h3>Conclusion</h3> This novel in vitro model, demonstrated significant modulation of α4β7 lymphocyte adhesion to the ligand MAdCAM-1 with an anti-β7 antibody. This highly controlled model system provides a more physiological representation of chemokine driven responsiveness than previously published chemotaxis or adhesion assays, and thus the Cellix<sup>®</sup> platform may serve as a useful tool for the development and validation of future anti-lymphocyte adhesion therapeutics. This research supports the clinical investigation of therapeutics targeting the β7 subunit or α4β7 heterodimer in this disease setting. <h3>Competing interests</h3> None declared.
Hypoxemia in the Postoperative Period
Authors: C. Ronald Stephen
Journal: JAMA (1965)

Within the past 20 years emphasis has been placed on the importance of maintaining normal acid-base balance in the postoperative period; it has become recognized that an adequate stir-up regimen, 1 coupled with proper ventilation, assisted by mechanical ventilators if necessary, provides the key in this respect. Owing to recent technical developments, attention at present is being focused on the degree to which oxygenation is being maintained during and after surgery. Reports have indicated that hypoxemia, according to accepted values, may be present more often than believed. 2 Arterial blood gas  were determined in surgical patients preoperatively, during surgery, and in the immediate postoperative period. In this way, control values may be compared with those found during and after the altered conditions imposed by surgery and anesthesia.  Methods  In all patients, arterial blood samples were obtained from an indwelling needle in the radial, ulnar, or brachial artery. Samples were
Interleukin 10–Mediated Immunosuppression by a Variant CD4 T Cell Epitope of Plasmodium falciparum
Authors: Magdalena Plebanski, Katie L Flanagan, Edwin A.M Lee, William H.H Reece, Keith Hart, Colin Gelder, Geraldine Gillespie, Margaret Pinder, Adrian V.S Hill
Journal: Immunity (1999)
The Low Anion Gap
Authors: Albert A. Keshgegian
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The article by Goldstein et al on the anion gap provides a comprehensive summary of the range of anion gap in a hospitalized population, but some of the conclusions that the authors draw may not necessarily be justified by the data. The authors assembled the data on anion gap in a large number of hospitalized patients, obtained a mean ±2 SDs, assumed that values below this range are low, and found only a few patients with a low anion gap. However, the appropriate comparison would have been with the range of anion gap found in a healthy population. A number of studies have shown that the range found in a healthy population is narrower than the range found in hospitalized patients (as reviewed by Witte et al<sup>1</sup>). It is obvious that the high values in hospital patients will include those in renal failure and other forms
Acquired facial atrophy: A neglected clinical sign of POEMS syndrome
Authors: Claude Bachmeyer
Journal: American Journal of Hematology (2011)

Acquired facial atrophy: a neglected clinical sign of POEMS syndrome I read with great interest the review on POEMS syndrome by Angela Dispenzieri [1].As indicated by the author, skin lesions are frequent in this syndrome, some characteristic, and considered as minor criteria of POEMS syndrome.These include hyperpigmentation, hypertrichosis, and glomeruloid hemangioma, requiring a whole skin examination.However, the author does not mention acquired facial atrophy observed in more than half of patients in a recent dermatologic series including 21 patients conducted at our institution [2].This clinical manifestation is similar to the lipoatrophy observed in HIV-infected patients under highly active antiretroviral therapy with protease inhibitors and nucleoside reverse transcriptase inhibitors as a part of the metabolic or lipodystrophy syndrome [3], or in patients with autoimmune diseases and alternate complement pathway abnormalities [4], including lupus panniculitis [5].In our institution, we consider that POEMS syndrome should be evoked in patients not under antiretroviral treatment presenting with acquired facial lipoatrophy not preceded by a deep skin infiltration as observed in lupus panniculitis, when associated with polyradiculoneuropathy and monoclonal gammopathy.
Nuclear Receptor/AP-1 Interaction*
Authors: MAGNUS PFAHL
Journal: Endocrine Reviews (1993)

NUCLEAR receptors mediate the signals of a broad variety of fat-soluble hormones, including the steroid and vitamin D3 hormones, thyroid hormones, and vitamin A-derived hormones and analogs (retinoids). The receptors represent one of the largest transcription factor families known (reviewed in Refs. 1–3). Only some of the members are ligand-binding receptors, while others are "orphan receptors" for which specific ligands have not yet been identified and may not exist. These proteins may therefore function as constitutive or negative transcription factors, or coregulators of ligand-binding receptors. The receptors regulate gene transcription by interacting with specific DNA sequences (called response elements) that are usually located in the promoter regions of the responsive genes. All receptors contain a highly conserved cysteine-rich region, the DNA- binding domain (DBD) that forms two "zinc-finger" structures that allow protein-DNA as well as proteinprotein interaction (4). A second but less well conserved region is found in all receptors in the hydrophobic carboxyterminal half and is usually referred to as the ligand-binding domain (LBD). In addition to ligand recognition, this domain encodes receptor dimerization (5–7) and transactivation (6, 8), or repressor functions (6, 9).
Prevention of Bacterial Endocarditis-Reply
Authors: Adnan S. Dajani
Journal: JAMA (1991)

In Reply.—  No recommendations can cover all possible groups or situations. Neurogenic bladder dysfunction treated with long-term intermittent catheterization is a special situation for which prophylaxis is not recommended. The frequency of catheterization and the large variety of bacterial species that may be present in the bladder make prophylaxis impossible to accomplish in this situation. Continuous proxphylaxis during intermittent catheterization would promote the emergence of resistant organisms. Symptomatic urinary tract infection should be treated when it occurs.  Concerning the letter from Stierer and Sterchele and the letter from McMorrow and Nahata, we offer the following comments: In the previous recommendations from the American Heart Association concerning bacterial endocarditis prophylaxis,1the regimen for erythromycin in patients who are allergic to penicillin was 1.0 g, followed by 500 mg, without reference to a specific preparation of the drug. Because of the complex pharmacokinetics associated with various erythromycin preparations, as well as
The Wirsungorrhagies: Causes and Management in 14 Patients
Authors: F. Dinu, J. Devière, A. Van Gossum, J. Golzarian, L. Dussaussois, M. Delhaye, M. Cremer
Journal: Endoscopy (1998)

Background and Study Aims: Wirsungorrhagy is an extremely rare cause of upper gastrointestinal bleeding. The present study describes 14 cases observed over a seven-year period.
Characteristics of Opioid Prescriptions in 2009
Authors: Nora D. Volkow
Journal: JAMA (2011)

ing data at all or pooling data using network meta-analysis, we chose the latter; indeed network meta-analysis has been shown to potentially give more reliable results because of the integration of additional information. 5,6Although studies included in our review were from different sources, they were all randomized controlled trials and hence contrasts between treatment groups within each study should be comparable.In addition, we focused only on CP/CPPS categories IIIA and IIIB to reduce heterogeneity due to disease severity and focused on outcomes measured using National Institutes of Health Chronic Prostatitis Symptom Index scales to reduce heterogeneity due to measurement error.Nevertheless, we explored potential discrepancies in treatment effects between direct and network meta-analysis results using the standardized normal method (z). 5,6Directions of treatment effect for the 2 methods were identical for all 12 comparisons; moreover, the magnitude of the effects between the 2 methods were similar except for ␣-blocker vs placebo, where z was large and reached statistical significance (2.9380, P=.003).We believe that this is an example of increased precision of treatment effects due to the network method "borrowing" information from indirect comparisons.Third, Jackson et al disagree that study data should be expanded using a Stata command so that it could be included in the meta-analysis, questioning how we could know the distribution of data.We only used this command for the treatment responsiveness outcome, which is a dichotomous outcome and does not need any assumption about distribution, normal or otherwise.We believe that using all available data, rather than omitting studies, is an advantage and will lead to more valid estimates.
PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus–Induced Liver Carcinogenesis
Authors: Hao Zhang, Ahmed Diab, Huitao Fan, Saravana Kumar Kailasam Mani, Ronald Hullinger, Philippe Merle, Ourania Andrisani
Journal: Cancer Research (2015)

Abstract Elucidating mechanisms of hepatitis B virus (HBV)–mediated hepatocarcinogenesis is needed to gain insights into the etiology and treatment of liver cancer. Cells where HBV is replicating exhibit increased expression of Plk1 kinase and reduced levels of two transcription repression factors, SUZ12 and ZNF198. SUZ12 is an essential subunit of the transcription repressive complex PRC2. ZNF198 stabilizes the transcription repressive complex composed of LSD1, Co-REST, and HDAC1. These two transcription repressive complexes are held together by binding the long noncoding RNA HOTAIR. In this study, we linked these regulatory events mechanistically by showing that Plk1 induces proteasomal degradation of SUZ12 and ZNF198 by site-specific phosphorylation. Plk1-dependent ubiquitination of SUZ12 and ZNF198 was enhanced by expression of HOTAIR, significantly reducing SUZ12 and ZNF198 stability. In cells expressing the HBV X protein (HBx), downregulation of SUZ12 and ZNF198 mediated global changes in histone modifications. In turn, HBx-expressing cells propagated an altered chromatin landscape after cell division, as exemplified by changes in histone modifications of the EpCAM promoter, a target of PRC2 and LSD1/Co-REST/HDAC1 complexes. Notably, liver tumors from X/c-myc bitransgenic mice exhibited downregulation of SUZ12 and ZNF198 along with elevated expression of Plk1, HOTAIR, and EpCAM. Clinically, similar effects were documented in a set of HBV-related liver tumors consistent with the likelihood that downregulation of SUZ12 and ZNF198 leads to epigenetic reprogramming of infected hepatocytes. Because both Plk1 and HOTAIR are elevated in many human cancers, we propose that their combined effects are involved in epigenetic reprogramming associated broadly with oncogenic transformation. Cancer Res; 75(11); 2363–74. ©2015 AACR.
The Managerial Revolution in Higher Education
Authors: Vernon E. Wilson
Journal: JAMA (1967)

This book should be on the required reading list for all educational administrators and, in addition, for faculty members who have expressed interest and opinions on the topic of administration. Rourke and Brooks set forth clearly a number of the major problems faced by universities in an unparalleled period of expansion in numbers of students, knowledge, and diversification of that knowledge. Unfortunately the authors do not clearly distinguish the role of research investigator in administration from that of advisor. Arguments for procedures or changes are interwoven with the research results. While the reader may be quite ready to accept the research as needed and valid, some of the global recommendations set forth are subject to severe question since they deal primarily with supportive functions of the university while proportionately neglecting its central objectives. The study would have been strengthened by a thorough review of the way in which faculty are
Early regrafting after primary liver transplantation carries increased risk of death
Authors: S. Balupuri, D. Manas, M. Thick, D. Talbot
Journal: BMJ (1999)

EDITOR—The mortality among patients with primary liver grafts is remarkably low, and attention has been focused on the survival of recipients of a second graft. A review by a group in Birmingham found that in 1087patients who received liver transplants the overall survival among those with primary grafts was 78% (K F Yoong et al, eighth congress of the European Society for Organ Transplantation, Budapest, September 1997). Survival after receipt of a second graft depended on the …
Creating and Validating an Algorithm to Measure AIDS Mortality in the Adult Population using Verbal Autopsy
Authors: Ben A Lopman, Ruanne V Barnabas, J. Ties Boerma, Godwin Chawira, Kezia Gaitskell, Tara Harrop, Peter Mason, Christl A Donnelly, Geoff P Garnett, Constance Nyamukapa, Simon Gregson
Journal: PLoS Medicine (2006)

Vital registration and cause of death reporting is incomplete in the countries in which the HIV epidemic is most severe. A reliable tool that is independent of HIV status is needed for measuring the frequency of AIDS deaths and ultimately the impact of antiretroviral therapy on mortality.A verbal autopsy questionnaire was administered to caregivers of 381 adults of known HIV status who died between 1998 and 2003 in Manicaland, eastern Zimbabwe. Individuals who were HIV positive and did not die in an accident or during childbirth (74%; n = 282) were considered to have died of AIDS in the gold standard. Verbal autopsies were randomly allocated to a training dataset (n = 279) to generate classification criteria or a test dataset (n = 102) to verify criteria. A rule-based algorithm created to minimise false positives had a specificity of 66% and a sensitivity of 76%. Eight predictors (weight loss, wasting, jaundice, herpes zoster, presence of abscesses or sores, oral candidiasis, acute respiratory tract infections, and vaginal tumours) were included in the algorithm. In the test dataset of verbal autopsies, 69% of deaths were correctly classified as AIDS/non-AIDS, and it was not necessary to invoke a differential diagnosis of tuberculosis. Presence of any one of these criteria gave a post-test probability of AIDS death of 0.84.Analysis of verbal autopsy data in this rural Zimbabwean population revealed a distinct pattern of signs and symptoms associated with AIDS mortality. Using these signs and symptoms, demographic surveillance data on AIDS deaths may allow for the estimation of AIDS mortality and even HIV prevalence.
The GSTP1 gene variant rs1695 is not associated with an increased risk of multiple sclerosis
Authors: José A G Agúndez, Elena García-Martín, Carmen Martínez, Julián Benito-León, Jorge Millán-Pascual, María Díaz-Sánchez, Patricia Calleja, Diana Pisa, Laura Turpín-Fenoll, Hortensia Alonso-Navarro, Lucía Ayuso-Peralta, Dolores Torrecillas, Esteban García-Albea, José Francisco Plaza-Nieto, Félix Javier Jiménez-Jiménez
Journal: Cellular and Molecular Immunology (2014)
Pulmonary and hepatic effects of inhaled ozone in rats.
Authors: D L Laskin, K J Pendino, C J Punjabi, M Rodriguez del Valle, J D Laskin
Journal: Environmental Health Perspectives (1994)

Nitric oxide is a highly reactive molecule that has been implicated in host defense and in tissue injury. In the present studies we analyzed the effects of brief exposure of rats to inhaled ozone on production of this mediator by lung macrophages and type II epithelial cells. We found that ozone exposure (1-2 ppm, 3 hr) induced a marked increase in spontaneous nitric oxide production by alveolar (AM) and interstitial macrophages, as well as type II cells. These effects were apparently due to increased expression of inducible nitric oxide synthase protein and mRNA, which was evident in vitro in isolated cells and in situ in histologic sections. Macrophages and epithelial cells from ozone-treated rats were also sensitized to produce increased amounts of nitric oxide in response to inflammatory cytokines such as interferon-gamma, a response that was also mediated by inducible nitric oxide synthase. Unexpectedly, we also discovered that brief inhalation of ozone caused dramatic effects on the liver, including increased production of nitric oxide by hepatocytes and enhanced protein synthesis. These data suggest that this inhaled irritant induces an acute phase response. Additional studies indicate that AM from ozone-treated rats produced significantly more tumor necrosis factor-alpha and interleukin-1 than did cells from control animals. Elevated levels of tumor necrosis factor-alpha were also noted immunohistochemically in both lung and liver tissue. These results indicate that the extrapulmonary effects of ozone may be mediated by inflammatory cytokines released by activated lung macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Coexpression of P <sub>2Y</sub> and P <sub>2U</sub> Receptors on Aortic Endothelial Cells
Authors: Didier Communi, Eric Raspe, Sabine Pirotton, Jean-Marie Boeynaems
Journal: Circulation Research (1995)

Abstract Depending on the vascular bed considered, the actions of ATP on the endothelium are mediated by either P 2Y or P 2U receptors. The two types of receptors seem to coexist on bovine aortic endothelial cells, where they are both coupled to phospholipase C. In this study, we have investigated whether they are truly coexpressed on the same cells and whether their signaling pathways diverge beyond phospholipase C activation. Measurements of [Ca 2+ ] i in single cells showed that almost all bovine aortic endothelial cells are responsive to both 2-methylthio-ATP (2MeSATP), an agonist of P 2Y receptors, and UTP, an agonist of P 2U receptors. UTP stimulated the release of prostacyclin from freshly isolated bovine aortic endothelial cells, even when they were exposed to cycloheximide at the time of their collection: this indicates that P 2U receptors must already be expressed on endothelial cells in situ and do not appear during cell culture. The time course of inositol phosphate (InsP) accumulation and the relative proportion of Ins(1,4,5)P 3 , Ins(1,3,4,5)P 4 , and Ins(1,3,4)P 3 were similar in cells stimulated by 2MeSATP or UTP. UTP and 2MeSATP both stimulated the hydrolysis of phosphatidylcholine by phospholipase D, as reflected by the release of [ 3 H]choline from prelabeled cells. The responses to both agents were blocked after downregulation of protein kinase C, resulting from a prolonged exposure to phorbol 12-myristate 13-acetate: this blockade occurred at a step distal to phospholipase C activation. A single difference between the two pathways has been identified: the effect of 2MeSATP on InsP 3 was significantly more inhibited after a short exposure to phorbol 12-myristate 13-acetate than that of UTP. This discrepancy is consistent with the involvement of distinct G proteins in the activation of phospholipase C by P 2Y and P 2U receptors.
The Occurrence of Psychiatric Illness in Systemic Lupus Erythematosus
Authors: SAMUEL B. GUZE
Journal: American Journal of Psychiatry (1967)

A systematic study of 101 consecutive patients with definite or suspected systemic lupus erythematosus (SLE) revealed that psychiatric disorders are more frequent among these patients than would be expected among general medical patients. The author suggests that the psychiatric disorders are intrinsically related to the SLE rather than representative of separate psychiatric illnesses precipitated by the SLE or its treatment.
Relationship of Limited Joint Mobility to Abnormal Foot Pressures and Diabetic Foot Ulceration
Authors: Devaka JS Fernando, Ewan A Masson, Aristidis Veves, Andrew JM Boulton
Journal: Diabetes Care (1991)

To investigate the role of limited joint mobility (LJM) in causing abnormal foot pressures and foot ulceration.The subjects were recruited from a general diabetes clinic where patients were screened for neuropathy, retinopathy, and elevated plantar foot pressure. Sixty-four patients in five groups were matched by age and sex in the following groups: group 1, patients with LJM and neuropathy; group 2, nonneuropathic diabetic patients with LJM; group 3, patients with neuropathy and no LJM; group 4, diabetic control subjects; and group 5, nondiabetic control subjects. Joint mobility was assessed in the foot at subtalar and metatarsophalangeal joints; plantar foot pressures were assessed by optical pedobarography and neuropathic status by a Biothesiometer and electrophysiology.Joint mobility was reduced at both sites in groups 1 and 2 compared with groups 3, 4, and 5 (P less than 0.001). Plantar foot pressures were significantly higher in groups 1 and 2 compared with groups 3, 4, and 5 (P less than 0.001). No differences in plantar foot pressures were observed between groups 1 and 2. There were strong correlations between plantar foot pressures and joint mobility in the foot (r = -0.7, P less than 0.001). Previous foot ulceration was present in 65% of patients in group 1, none in group 2, and 5% in group 3.1) LJM may be a major factor in causing abnormally high plantar foot pressures, 2) abnormal plantar foot pressures alone do not lead to foot ulceration, and 3) LJM contributes to foot ulceration in the susceptible neuropathic foot.