tbuckley/cabot-search huggingface dataset:
Involvement of Multiple <i>cis</i> Elements in Basal- and α-Adrenergic Agonist–Inducible Atrial Natriuretic Factor Transcription
Authors: Amy B. Sprenkle, Susan F. Murray, Christopher C. Glembotski
Journal: Circulation Research (1995)

Abstract In the present study, cis elements in the 5′-flanking sequence (FS) of the rat atrial natriuretic factor (ANF) gene involved in regulating basal and α 1 -adrenergic–inducible transcription were investigated. Truncation analyses using ANF-luciferase reporter constructs transfected into primary neonatal rat cardiac myocytes showed that an A/T-rich serum response element (SRE) at −114 bp of the ANF 5′-FS, which bound serum response factor (SRF), was required for basal and inducible transcription. In constructs composed of 134 bp of rat ANF 5′-FS driving luciferase (ANF-134Luc), mutations in the SRE at −114 bp disrupted SRF binding and ANF promoter activity. However, the same mutations in ANF-638Luc had little effect, suggesting a collaborating role for more distal sequences, such as the other SRE in ANF-638 at −406 bp. In ANF-638Luc, mutations in the SRE at −406 bp that disrupted SRF binding to that site decreased ANF reporter activity by only 25%; however, mutating both of the SREs completely blocked α 1 -adrenergic–inducible activity. Mutation analyses showed that an ••• (SP-1)–like site at −69 bp, shown previously to confer inducibility in reporters with 134 bp of ANF 5′-FS, was not required in ANF-638Luc. However, double mutants in the SP-1–like region and either SRE completely blocked α 1 -adrenergic–inducible ANF promoter activity. These findings emphasize that no single element is responsible for α 1 -adrenergic agonist–regulated ANF transcription but that the SREs at −114 and −406 bp and the SP-1–like sequence at −69 bp mediate the effect in collaboration.
Liver transplantation for unresectable hepatocellular carcinoma in normal livers
Authors: Hynek Mergental, Rene Adam, Bo-Goran Ericzon, Piotr Kalicinski, Ferninand Mühlbacher, Krister Höckerstedt, Jürgen L. Klempnauer, Styrbjörn Friman, Christoph E. Broelsch, Georges Mantion, Carlos Fernandez-Sellez, Bart van Hoek, Josef Fangmann, Jacques Pirenne, Paolo Muiesan, Alfred Königsrainer, Darius F. Mirza, Jan Lerut, Olivier Detry, Yves-Ptrice Le Treut, Vincenzo Mazzaferro, Florian Löhe, Marina Berenguer, Pierre-Alain Clavien, Xavier Rogiers, Jacques Belghiti, Laslo Kóbori, Patrizia Burra, Philippe Wolf, Wolfgang Schareck, Przemyslaw Pisarski, Aksel Foss, Franco Filipponi, Marek Krawczyk, Martin Wolff, Jan M. Langrehr, Keith Rolles, Neville Jamieson, Wim C.J. Hop, Robert J. Porte
Journal: Journal of Hepatology (2012)
The Third Stage of Labour
Authors: A. H. F. Barbour
Journal: BMJ (1896)

lFxB. 29, 1Sg.-Taking such figres as correct, the placenta would in all probability be found (a) in the first or O.L.A. position, 67 per cent.upon the posterior wall and to the right side; (b) in the secd-or O.D.A. position, io per cent.upon the posterior wall and to the left side; (c) in the third or O.D.P. position, 20 per cent.upon the anterior wall and to the left side; (d) in the fourth or O.L.P. position, 3 per cent.upon the anterior wall and to the right side.Upon adding the first and second together we would have 77 per cent.upon the posterior wall, and with the third and fourth 23 per cent.In Vienna, out of 32 cases of Caesarean section, 12 had the placenta in front.This, along with my own experience, which is 77 per cent.dorso-anterior and 23 per cent.dorso-posterior, would give 70 per cent.dorso-anterior and 30 per cent.dorso-posterior
Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes
Authors: Hussein H. Aly, Koichi Watashi, Makoto Hijikata, Hiroyasu Kaneko, Yasutugu Takada, Hiroto Egawa, Shinji Uemoto, Kunitada Shimotohno
Journal: Journal of Hepatology (2006)
Significance of skp2 expression in primary breast cancer.
Authors: Hideto Sonoda, Hiroshi Inoue, Kazuhiko Ogawa, Tohru Utsunomiya, Taka-aki Masuda, Masaki Mori
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: We previously reported the p27 expression level to be an independent prognostic factor, and a high S-phase kinase-associated protein 2 (Skp2) expression level was significantly correlated with a poor prognosis in patients with gastric cancer. We herein examined the Skp2 expression in breast cancer and attempted to identify any associations between the Skp2 expression status and either the clinicopathologic variables or the patient's prognosis. EXPERIMENTAL DESIGN: We established four Skp2-transfected breast cancer cell lines and assessed the correlations between the Skp2 and p27 expressions using real-time reverse transcription-PCR and a Western blot analysis. We then analyzed the clinicopathologic significance of Skp2 mRNA expression in 169 Japanese patients with breast cancer. An immunohistochemical analysis was also done. RESULTS: The p27 protein expression markedly decreased after Skp2 transfection, whereas no alteration in the p27 mRNA expression was observed. The Skp2 protein expression level as determined by immunohistochemical staining thus showed a significant correlation with the Skp2 mRNA expression (P = 0.001) and a significant inverse correlation with the p27 protein expression (P = 0.042). The patients with a high Skp2 gene expression were significantly younger than those with a low expression (P = 0.002). The prognosis of patients with a high Skp2 expression was significantly (P = 0.022) poorer than for those with a low expression. Moreover, a high expression of Skp2 was an independent variable that correlated with a shorter disease-free survival (relative risk, 3.33; 95% confidence interval, 1.296-8.578; P = 0.013). CONCLUSIONS: The present results suggest that Skp2 may play an important role particularly in young breast cancer, and it is also considered to have strong independent prognostic potential and thus may prove to be a useful target for the treatment of breast cancer.
Please Pack Open Your Dirty Wounds!
Authors: Stephen M. Cohn
Journal: JAMA Surgery (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
A Multicenter Phase II Trial of Thalidomide and Celecoxib for Patients with Relapsed and Refractory Multiple Myeloma
Authors: H Miles Prince, Linda Mileshkin, Andrew Roberts, Vinod Ganju, Craig Underhill, John Catalano, Richard Bell, John F. Seymour, David Westerman, Paul J. Simmons, Kate Lillie, Alvin D. Milner, Juliana Di Iulio, Jerome B. Zeldis, Robert Ramsay
Journal: Clinical Cancer Research (2005)

Abstract Preclinical data indicates that cyclooxygenase-2 (COX-2) inhibition impairs plasma cell growth and potentially synergizes with thalidomide. We performed a trial in previously treated patients with myeloma using thalidomide up to a maximum dose of 800 mg/d with celecoxib (400 mg bid). Outcomes were compared with a prior trial of thalidomide. Sixty-six patients with median age of 67 (range, 43-85) received a median dose of thalidomide and celecoxib of 400 and 800 mg/d, respectively, with median durations of treatment of 27 and 13 weeks, respectively. The most common toxicities associated with premature discontinuation of celecoxib (n = 30 of 53, 57%) were fluid retention and deterioration of renal function. Overall response rate (RR) was 42% and with 20 months median follow-up; the actuarial median progression-free survival and overall survival were 6.8 and 21.4 months, respectively. Unlike our prior study, age &amp;gt;65 years was not predictive of inferior RR due to improvement in RR in older patients with the combination (37% versus 15%, P = 0.08). The RR was superior in patients who received a total dose of celecoxib exceeding 40 g in the first 8 weeks of therapy (62% versus 30%, P = 0.021). Progression-free survival and overall survival were also improved. Other predictors for inferior progression-free survival were age &amp;gt;65 years (P = 0.016) and elevated β2-microglobulin (P = 0.017). This study provides evidence that the addition of high-dose celecoxib adds to the antimyeloma activity of thalidomide but this comes with unacceptable toxicity. Future studies should use newer COX-2 inhibitors with thalidomide, or their respective derivatives.
<i>Helicobacter pylori</i>Modulates the T Helper Cell 1/T Helper Cell 2 Balance through Phase-variable Interaction between Lipopolysaccharide and DC-SIGN
Authors: Mathijs P. Bergman, Anneke Engering, Hermelijn H. Smits, Sandra J. van Vliet, Ad A. van Bodegraven, Hans-Peter Wirth, Martien L. Kapsenberg, Christina M.J.E. Vandenbroucke-Grauls, Yvette van Kooyk, Ben J. Appelmelk
Journal: The Journal of Experimental Medicine (2004)

The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le− variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.
Graft-versus-Leukemia Target Antigens in Chronic Myelogenous Leukemia Are Expressed on Myeloid Progenitor Cells
Authors: Catherine J. Wu, Melinda Biernacki, Jeffery L. Kutok, Shelby Rogers, Linyun Chen, Xiao-Feng Yang, Robert J. Soiffer, Jerome Ritz
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Donor lymphocyte infusion (DLI) reliably induces durable remission in 75% to 80% of patients with relapsed chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation. We previously reported the identification of a high titer–specific immunoglobulin G response against two novel leukemia-associated antigens, CML28 and CML66, which correlated with immune-induced remission. The present studies characterize expression of CML28 and CML66 in primary hematopoietic tissues. Experimental Design: Specific monoclonal antibodies to CML28 and CML66 were developed and used to detect antigen expression in leukemia cell lines and primary leukemia tissue on Western blot and immunohistochemistry. Expression patterns were confirmed by antigen-specific real-time PCR. Results: Both CML28 and CML66 were highly expressed in leukemic blasts from patients with acute myelogenous leukemia and CML blast crisis but barely detectable in normal bone marrow, normal peripheral blood, or leukemic cells from patients with stable-phase CML. In contrast, purified CD34+ progenitors from normal individuals and patients with stable-phase CML expressed high levels of CML28 and CML66 transcript and protein. Immunohistochemical staining for CML66 confirmed rare staining of myeloid precursors in normal marrow and diffuse staining of myeloblastic cells in acute myelogenous leukemia and blast crisis CML marrows. Conclusions: The expression patterns of CML28 and CML66 are strikingly similar and suggest that antigen expression may play a role in shaping the post-DLI antibody repertoire. The CD34+ restricted pattern of expression of CML28 and CML66 is particularly relevant in light of the notion that DLI likely exerts its curative effect by targeting antigens present in self-renewing malignant progenitor populations in CML.
Patient-Centered Decisions in Primary Care—Reply
Authors: Floyd J. Fowler, Bethany S. Gerstein, Michael J. Barry
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Celiac CTLs change their stripes
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Gut-resident T cells morph into disease-causing natural killer (NK)-like cells during Celiac disease (CD), according to Meresse and colleagues on page 1343.

For people with CD, dietary gluten is the enemy. Gluten consumption somehow stresses the epithelial lining of the gut and triggers the activation of gluten-specific CD4+ T cells. CD8+ cytolytic T lymphocytes (CTLs) in the gut also expand during CD, but their role in disease is less clear.

Meresse and colleagues now show that gut CTLs from patients with CD express high levels of the activating NK cell receptor NKG2C, which is typically expressed only by NK cells. Binding of NKG2C by its receptor HLA-E (which was expressed on diseased gut epithelium) caused the CTLs to kill NK target cell lines, proliferate, and produce interferon (IFN)-γ—all in the absence of T cell receptor (TCR) ligation. In short, it caused them to act like NK cells.

This induction of NKG2C on gut CTLs might free them from their normal TCR-mediated activation constraints, thus unleashing them on gluten-stressed gut cells. NKG2C+ CTLs from patients with CD showed that these cells—but not normal CTLs—also expressed other activating NK cell receptors, suggesting that the cells get reprogrammed during CD.

Why would the immune system de-evolve antigen-restricted CTLs into indiscriminate killers? The authors speculate that this may have developed to help clear local infections, as NK cells have a hard time penetrating tissues, but that the process is taken to the extreme during CD.
A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability.
Authors: N P Restifo, P J Spiess, S E Karp, J J Mulé, S A Rosenberg
Journal: The Journal of Experimental Medicine (1992)

To be recognized by CD8+ T lymphocytes, target cells must process and present peptide antigens in the context of major histocompatibility complex (MHC) class I molecules. The nonimmunogenic, low class I-expressing, methylcholanthrene (MCA)-induced murine sarcoma cell line, MCA 101, is a poor presenter of endogenously generated viral antigens to specific CD8+ T lymphocytes and cannot be used to generate tumor infiltrating lymphocytes (TIL). Since interferon gamma (IFN-gamma) has been shown to upregulate three sets of molecules important for antigen processing and presentation, we retrovirally transduced wild-type MCA 101 (101.WT) tumor with the mIFN-gamma cDNA to create the 101.NAT cell line. Unlike 101.WT, some clones of retrovirally transduced 101.NAT tumor expressed high levels of class I, and could be used to generate CD8+ TIL. More importantly, these TIL were therapeutic in vivo against established pulmonary metastases from the wild-type tumor. Although not uniformly cytotoxic amongst several separate cultures, these TIL did specifically release cytokines (IFN-gamma and tumor necrosis factor-alpha) in response to 101.WT targets. 101.WT's antigen presentation deficit was also reversed by gene modification with mIFN-gamma cDNA. 101.NAT had a greatly improved capacity to present viral antigens to CD8+ cytotoxic T lymphocytes. These findings show that a nonimmunogenic tumor, incapable of generating a CD8+ T cell immune response, could be gene-modified to generate a therapeutically useful immune response against the wild-type tumor. This strategy may be useful in developing treatments for tumor histologies not thought to be susceptible to T cell-based immunotherapy.
S113 Haemophilus influenzae stimulation of alveolar macrophages from COPD patients; effects of corticosteroids: Abstract S113 Table 1.
Authors: R Khalaf, S Lea, H Metcalfe, D Singh
Journal: Thorax (2013)

<h3>Background</h3> The lower airways of COPD patients are often chronically colonised by bacteria such as Non-typeable <i>Haemophilus influenza</i> (NTHI). Bacteria are a common cause of COPD exacerbations. Corticosteroids are often used to prevent and treat COPD exacerbations. The aim of this study was to investigate the effect of corticosteroids on the <i><i>in vitro</i></i> inflammatory response of COPD alveolar macrophages (AM) to NTHI infection. We also investigated the cell signalling pathways activated by NTHI infection. <h3>Methods</h3> AM from 12 COPD patients and 9 smoking controls were infected with live NTHI at multiplicity of infection (MOI) of 100:1 (bacteria: AM) for 24 hours. AM were pre-treated with dexamethasone (up to 1µM) for 1 hour. Supernatants were analysed for TNF-α, IL-6, IL-8 and IL-10 by ELISA. AM protein was extracted for Western blot analysis of nuclear factor κB (NFκB), p38 and extracellular regulated mitogen activated protein kinases (p38 and ERK) activation. <h3>Results</h3> NTHI stimulated release of TNF-α, IL-6, IL-8 and IL-10 (p &lt; 0.05) from both COPD patients and controls. TNF-α, IL-6 and IL-10 production was significantly inhibited by dexamethasone at 1 and 0.1µM (p &lt; 0.05). Inhibition of TNF-α and IL-6 release was significantly higher in AM from smokers compared to COPD patients. Dexamethasone had no effect on IL-8 production (see table 1). NTHI infection activated NFκB, p38 and ERK MAPK signalling pathways in AM. <h3>Conclusion</h3> NTHI infection stimulated COPD AM to release inflammatory cytokines which are only partially responsive to corticosteroids; importantly, there was no suppression of the neutrophil chemoattractant IL-8. The production of this corticosteroid resistant chemokine is associated with NF-κB and MAPK activation; these signalling pathways drive bacteria induced inflammation in COPD airways.
Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs
Authors: Felicitas S. Boretti, Paul W. Buehler, Felice D’Agnillo, Katharina Kluge, Tony Glaus, Omer I. Butt, Yiping Jia, Jeroen Goede, Claudia P. Pereira, Marco Maggiorini, Gabriele Schoedon, Abdu I. Alayash, Dominik J. Schaer
Journal: Journal of Clinical Investigation (2009)

Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hb-induced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO- and O2-binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.
The Factors Influencing the Circulation Time
Authors: MORTON LEE PEARCE, ALVIN E. LEWIS, MELVIN R. KAPLAN
Journal: Circulation (1952)

A mathematical analysis of the relationship of cardiac output and heart-lung blood volume to observed circulation time is presented. The theoretic conclusions are substantiated by an experiment in which it is shown that diluting the amount of indicator used prolongs the observed circulation time through the heart and lungs.
A search for mycoplasma infections in patients with chronic bronchitis
Authors: J. D. Cherry, D. Taylor-Robinson, H. Willers, A. C. Stenhouse
Journal: Thorax (1971)

Throat and bronchoscopy specimens for mycoplasma isolation studies were collected from 22 patients with chronic bronchitis and 20 patients without chronic bronchitis. Twenty-six of 50 patients attending a chronic bronchitis clinic had throat, nasal, or sputum specimens collected for attempted mycoplasma isolation, and all of these patients had multiple serum samples taken for mycoplasma antibody studies. Mycoplasmas were recovered from throat and bronchoscopy specimens of the chronic bronchitic and non-bronchitic patients with about equal frequency. The concentration of organisms in the bronchoscopy specimens of two patients with chronic bronchitis was greater than in their throat specimens, suggesting downward spread and multiplication of mycoplasmas rather than contamination by passage of the bronchoscope. Eighty-three per cent of the rises in mycoplasma antibody titre in chronic bronchitic patients occurred during or immediately after an acute respiratory illness, and this relationship of rise in antibody titre to acute illness was significantly more frequent than rises in antibody titre not associated with illness. We suggest that mycoplasmas may be present in the bronchi of some patients suffering from chronic bronchitis and that, while such mycoplasma infections are often silent, they may become sufficiently active during infection by other agents to stimulate a mycoplasma antibody response.