tbuckley/cabot-search huggingface dataset:
Three alternative promoters of the rat gamma-glutamyl transferase gene are active in developing lung and are differentially regulated by oxygen after birth.
Authors: M Joyce-Brady, S M Oakes, D Wuthrich, Y Laperche
Journal: Journal of Clinical Investigation (1996)

The rat gamma-glutamyl transferase mRNA transcripts I, II, and III are derived from three alternative promoters, P(I), P(II), and P(III). In the adult only mRNA III is expressed in the lung. We show that mRNA III gene expression is developmentally regulated in the fetal lung; it is first expressed in gestation. In contrast to the adult lung, the fetal lung expresses mRNA I, II, and III. The switch from the fetal to the adult pattern of gammaGT mRNA expression begins within the first 24 h of birth and is complete by 10 d of age. gammaGT mRNA II disappears within 24 h, mRNA I disappears by 10 d leaving mRNA III as the sole transcript. Alveolar epithelial type 2 cells (AT2) isolated from the adult lung express only mRNA III. When cultured in 21% O2 mRNA III is maintained, but when cultured in 3% O2 the fetal pattern of mRNA I, II and III expression is induced. When AT2 cells in hypoxia are exposed to carbon monoxide, mRNA II is suppressed suggesting that a heme-binding protein (responsive to oxygen) may suppress mRNA II expression and may be responsible for the decrease in lung mRNA II seen after birth. A reporter gene under the control of DNA sequences from the gammaGT P(III) promoter is activated in transient transfection studies in response to hyperoxia, while a deletion construct retaining an antioxidant responsive element is not. Oxygen appears to regulate each of the alternative promoters of the gammaGT gene, such that P(II) is rapidly repressed by a heme-dependent mechanism, P(I), is more gradually repressed by a nonheme mechanism and P(III) is activated by a putative oxygen response element. We hypothesize that similar oxygen-dependent mechanisms regulate other genes in the developing lung at birth.
Antenatal Thyroid Screening and Childhood Cognitive Function
Authors: John H. Lazarus, Jonathan P. Bestwick, Sue Channon, Ruth Paradice, Aldo Maina, Rhian Rees, Elisabetta Chiusano, Rhys John, Varvara Guaraldo, Lynne M. George, Marco Perona, Daniela Dall'Amico, Arthur B. Parkes, Mohammed Joomun, Nicholas J. Wald
Journal: New England Journal of Medicine (2012)

Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function.We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T(4)). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T(4) levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 μg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments.Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], -1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, -2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results.Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age. (Funded by the Wellcome Trust UK and Compagnia di San Paulo, Turin; Current Controlled Trials number, ISRCTN46178175.).
CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel
Authors: D.L. Hertz, S. Roy, A.A. Motsinger-Reif, A. Drobish, L.S. Clark, H.L. McLeod, L.A. Carey, E.C. Dees
Journal: Annals of Oncology (2013)
The Medial Temporal Lobe and Recognition Memory
Authors: H. Eichenbaum, A.P. Yonelinas, C. Ranganath
Journal: Annual Review of Neuroscience (2007)

The ability to recognize a previously experienced stimulus is supported by two processes: recollection of the stimulus in the context of other information associated with the experience, and a sense of familiarity with the features of the stimulus. Although familiarity and recollection are functionally distinct, there is considerable debate about how these kinds of memory are supported by regions in the medial temporal lobes (MTL). Here, we review evidence for the distinction between recollection and familiarity and then consider the evidence regarding the neural mechanisms of these processes. Evidence from neuropsychological, neuroimaging, and neurophysiological studies of humans, monkeys, and rats indicates that different subregions of the MTL make distinct contributions to recollection and familiarity. The data suggest that the hippocampus is critical for recollection but not familiarity. The parahippocampal cortex also contributes to recollection, possibly via the representation and retrieval of contextual (especially spatial) information, whereas perirhinal cortex contributes to and is necessary for familiarity-based recognition. The findings are consistent with an anatomically guided hypothesis about the functional organization of the MTL and suggest mechanisms by which the anatomical components of the MTL interact to support the phenomenology of recollection and familiarity.
Characteristics of adrenoceptors and [3H]nitrendipine receptors of porcine vascular smooth muscle: differences between coronary artery and aorta.
Authors: J Nishimura, H Kanaide, M Nakamura
Journal: Circulation Research (1987)

Characteristics of the bindings of [3H](-)dihydroalprenolol, [125I](-)iodocyanopindolol, [3H]prazosin, [3H]yohimbine, and [3H]nitrendipine to porcine coronary membranes were investigated and the results compared with studies of porcine aortic membranes. In the equilibrium binding study carried out in sarcolemma-enriched fractions, there were no major differences in the Kd values of these radioligands between coronary artery and aorta. However, the densities of beta-, alpha 1-, and alpha 2-adrenoceptors and [3H]nitrendipine receptors of coronary artery were 258, 12, 12, and 561 fmol/mg protein, respectively, while those of aorta were 37, 525, 1,000, and 215 fmol/mg protein. beta-Adrenergic agonists competed with [3H](-)dihydroalprenolol binding sites in coronary artery, the order of potency being (-)isoproterenol greater than (-)norepinephrine greater than (-)epinephrine greater than (+)isoproterenol. In case of aorta, the order was (-)isoproterenol greater than (-)epinephrine greater than (-)norepinephrine. The competition by (+/-)bisoprolol (beta 1-selective antagonist) and ICI 118,551 (beta 2-selective antagonist) for [125I](-)iodocyanopindolol binding sites in coronary artery resulted in nonlinear Hofstee plots (beta 1:beta 2 = 90%:10%). In case of aorta, linear Hofstee plots were obtained. From these results, we conclude that coronary beta-receptors in pigs are predominantly of beta 1-type, while those of aorta are of beta 2-type; regarding the relative population of adrenoceptors, coronary artery is beta-dominant (beta/alpha = 11), while aorta is alpha-dominant (beta/alpha = 0.02); compared with alpha-adrenoceptors, coronary artery has a greater number of [3H]nitrendipine binding sites (nitrendipine/alpha-adrenoceptor = 23) than aorta (nitrendipine/alpha-adrenoceptor = 0.14).
Phase II Trial of Weekly Paclitaxel for Unresectable Angiosarcoma: The ANGIOTAX Study
Authors: Nicolas Penel, Binh Nguyen Bui, Jacques-Olivier Bay, Didier Cupissol, Isabelle Ray-Coquard, Sophie Piperno-Neumann, Pierre Kerbrat, Charles Fournier, Sophie Taieb, Marta Jimenez, Nicolas Isambert, Frédéric Peyrade, Christine Chevreau, Emmanuelle Bompas, Etienne G.C. Brain, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2008)

Purpose The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma. Patients and Methods Thirty patients were entered onto the study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m 2 on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles. Results The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities. Conclusion Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.
Phase I Dose Escalation, Pharmacokinetic and Pharmacodynamic Study of Naptumomab Estafenatox Alone in Patients With Advanced Cancer and With Docetaxel in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Hossein Borghaei, Katherine Alpaugh, Gunnar Hedlund, Göran Forsberg, Corey Langer, Andre Rogatko, Robert Hawkins, Svein Dueland, Ulrik Lassen, Roger B. Cohen
Journal: Journal of Clinical Oncology (2009)

Two phase I studies were conducted of ABR-217620 alone or in combination with docetaxel. This is a recombinant fusion protein consisting of a mutated variant of the superantigen staphylococcal enterotoxin E (SEA/E-120) linked to fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4.Patients with non-small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose escalation monotherapy [MONO] study). Doses were selected based on individual patient anti-SEA/E-120 titers pretreatment. Patients with NSCLC received 4 daily, escalating doses of ABR-217620 followed by docetaxel in 21-day cycles (ABR-217620 dose escalation combination with docetaxel [COMBO] study).Thirty-nine patients were enrolled in the MONO study and 13 were enrolled in the COMBO study. The monotherapy MTD was 26 microg/kg (NSCLC and PC) and 15 microg/kg (RCC). Dose-limiting toxicities (DLTs) in the MONO study were fever, hypotension, acute liver toxicity, and vascular leak syndrome. In the COMBO study, the MTD was 22 microg/kg (neutropenic sepsis). Adverse events included grade 1 to 2 fever, hypotension, nausea, and chills. Treatment caused a systemic increase of inflammatory cytokines and selective expansion of SEA/E-120 reactive T-cells. Tumor biopsies demonstrated T-cell infiltration after therapy. Fourteen patients (36%) had stable disease (SD) on day 56 of the MONO study. Two patients (15%) in the COMBO study had partial responses, one in a patient with progressive disease on prior docetaxel, and five patients (38%) had SD on day 56.ABR-217620 was well tolerated with evidence of immunological activity and antitumor activity.
PDGF-induced signaling in proliferating and differentiated vascular smooth muscle: Effects of altered intracellular Ca regulation
Authors: C EGAN, C WAINWRIGHT, R WADSWORTH, G NIXON
Journal: Cardiovascular Research (2005)

Platelet-derived growth factor-BB (PDGF)-induced intracellular signaling is involved in phenotypic modulation of vascular smooth muscle (VSM). This study has examined the PDGF-induced Ca2+ increase and the resultant effect on signaling pathways in proliferative compared with fully differentiated VSM.PDGF-induced changes in Ca2+ were measured in portal vein (PV) myocytes from 2-4-day-old (proliferating), compared to 6-week-old (differentiated), Sprague Dawley rats. Phospholipase C (PLC)gamma expression and activation of extracellular signal-regulated kinase (ERK) 1/2 was determined by immunoblotting or confocal immunolabelling. Activation of the Ca(2+)-dependent transcription factor, nuclear factor of activated T-cells (NFATc), was assessed by electromobility shift assay.PDGF increased the intracellular Ca2+ concentration in differentiated, but not in proliferating, PV myocytes. This is probably due to very low expression of PLC(gamma) in proliferating PV. In 6-week-old PV, PDGF stimulation induced nuclear translocation and activation of NFATc. PDGF did not induce NFATc activation in neonatal PV. PDGF-induced ERK1/2 activation was observed in both 2-4-day-old and 6-week-old PV. In 6-week-old PV, ERK1/2 activation was Ca(2+)-dependent and protein kinase C-dependent. However in 2-4-day-old PV, PDGF-induced ERK1/2 activation was via a Ca(2+)-independent, atypical protein kinase C. PLC(gamma) expression was also decreased in the neointima, compared to media, of balloon-injured rabbit subclavian arteries.The regulation of PDGF-induced Ca2+ increases by PLC(gamma) expression in VSM may provide a mechanism for coordinating different signaling pathways leading to activation of specific transcription factors. This may play an important role in the phenotypic modulation of VSM.
THE CEREBRAL AND PERIPHERAL UPTAKE OF AMMONIA IN LIVER DISEASE WITH AN HYPOTHESIS FOR THE MECHANISM OF HEPATIC COMA 12
Authors: Samuel P. Bessman, Alice N. Bessman
Journal: Journal of Clinical Investigation (1955)

Hepatic coma is a frequent terminal event in cirrhosis of the liver.Interest in its pathogenesis and treatment has been stimulated by recent observations that there is some relation between the increased blood ammonia level and the development of coma (24).
Radiological Investigation of the Small Intestine by Small Bowel Enema Technique
Authors: F. Pygott, D. F. Street, M. F. Shellshear, C. J. Rhodes
Journal: Gut (1960)

This paper records some experience with the Scott Harden technique of small intestinal intubation for performing small bowel enemas. It is particularly recommended for searching for obstructive or infiltrative lesions of the small intestine.
Nonpharmacologic Treatment of the Wolff-Parkinson-White Syndrome and other Supraventricular Tachycardias
Authors: E N Prystowsky, D L Packer, J J Schier, J E Lowe
Journal: Annual Review of Medicine (1990)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Treatment of psoriasis with topical NG-monomethyl- l-arginine, an inhibitor of nitric oxide synthesis
Authors: A.D. Ormerod, P. Copeland, S.A.A. Shah
Journal: British Journal of Dermatology (2000)

Journal Article Treatment of psoriasis with topical NG‐monomethyl‐ l‐arginine, an inhibitor of nitric oxide synthesis Get access A.D. Ormerod, A.D. Ormerod Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN, U.K. Dr A.D.Ormerod. E‐mail: a.d.ormerod@abdn.ac.uk Search for other works by this author on: Oxford Academic Google Scholar P. Copeland, P. Copeland Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.A.A. Shah S.A.A. Shah Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 985–990, https://doi.org/10.1046/j.1365-2133.2000.03483.x Published: 01 May 2000
Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS Patient Registry
Authors: Eitan Kerem, Laura Viviani, Anna Zolin, Stephanie MacNeill, Elpis Hatziagorou, Helmut Ellemunter, Pavel Drevinek, Vincent Gulmans, Uros Krivec, Hanne Olesen
Journal: European Respiratory Journal (2013)

Pulmonary insufficiency is the main cause of death in cystic fibrosis (CF). We analysed forced expiratory volume in 1 s (FEV1) data of 14,732 patients registered in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database in 2007. We used linear and logistic regressions to investigate associations between FEV1 % predicted and clinical outcomes. Body mass index (BMI), chronic infection by Pseudomonas aeruginosa, pancreatic status and CF-related diabetes (CFRD) showed a statistically significant (all p<0.0001) and clinically relevant effect on FEV1 % pred after adjusting for age. Patients with a lower BMI experience a six-fold increased odds ratio (95% CI 5.0-7.3) of having severe lung disease (FEV1 <40% pred) compared to patients with normal BMI. Being chronically infected with P. aeruginosa increases the odds ratio of severe lung disease by 2.4 (95% CI 2.0-2.7), and patients with pancreatic insufficiency experience a 2.0-fold increased odds ratio (95% CI 1.6-2.5) of severe lung disease compared to pancreatic sufficient patients. Patients with CFRD have a 1.8-fold increased odds ratio (95% CI 1.6-2.2) compared to patients not affected. These potential risk factors for pulmonary disease in patients with CF are to some degree preventable or treatable. We emphasise the importance of their early identification through frequent routine tests, the implementation of infection control measures, and a timely initiation of relevant therapies.
Angiotensinogen Gene–Activating Elements Regulate Blood Pressure in the Brain
Authors: Tadahiko Nishii, Atsushi Moriguchi, Ryuichi Morishita, Kazuo Yamada, Shigefumi Nakamura, Naruya Tomita, Yasufumi Kaneda, Akiyoshi Fukamizu, Hiroshi Mikami, Jitsuo Higaki, Toshio Ogihara
Journal: Circulation Research (1999)

Abstract —Although the angiotensinogen gene is a possible candidate as a determinant of hypertension, the molecular mechanisms of tissue angiotensinogen gene regulation have yet to be clarified. We identified essential transcription regulators of angiotensinogen production in the central nervous system using synthetic double-stranded oligodeoxynucleotides (ODNs) as “decoy” cis elements to block the binding of nuclear factors to promoter regions of the targeted gene. Using a gel mobility shift assay, angiotensinogen gene–activating element (AGE) 2 binding protein was detected in the brain nuclear extracts of both spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs). Importantly, the binding activity of AGE 2 and angiotensinogen mRNA level were significantly higher in the brain of SHRs than in that of WKYs. Using the decoy approach, we demonstrated a significant decrease in the blood pressure of SHRs by transfection of AGE 2 decoy, but not mismatched, ODNs into the lateral cerebroventricle, accompanied by a significant decrease in brain angiotensinogen concentration and mRNA, and angiotensin II level. That these effects, demonstrated herein, are due to central effects is confirmed by the fact that no changes in circulating levels of angiotensinogen or angiotensin II concentrations were observed. Notably, AGE 2 decoy ODNs did not decrease the blood pressure of WKYs. We conclude that the abnormal expression of AGE 2 binding protein in the central nervous system plays a crucial role in high blood pressure of a genetically hypertensive rat model.
Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness
Authors: K. C. Sumino, M. J. Walter, C. L. Mikols, S. A. Thompson, M. Gaudreault-Keener, M. Q. Arens, E. Agapov, D. Hormozdi, A. M. Gaynor, M. J. Holtzman, G. A. Storch
Journal: Thorax (2010)

<h3>Background</h3> A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers. <h3>Methods</h3> The prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness were investigated. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalised with acute respiratory illness over 12 months (n=283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician9s discretion. 27 inflammatory mediators were measured in a subset of the patients (n=64) using a multiplex immunoassay. <h3>Results</h3> 39 respiratory viruses were detected in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n=13), influenza virus (n=8), respiratory syncytial virus (n=6), human metapneumovirus (n=3), coronavirus NL63 (n=2), parainfluenza virus (n=2), adenovirus (n=1) and newly discovered viruses (n=4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon <i>γ</i>-inducible protein 10 (IP-10) (p&lt;0.001) and eotaxin-1 (p=0.017) in BAL. <h3>Conclusions</h3> Respiratory viruses can be found in patients with serious acute respiratory illness by use of PCR assays more frequently than previously appreciated. IP-10 may be a useful biomarker for respiratory viral infection.