tbuckley/cabot-search huggingface dataset:
Topical corticosteroid reduces inflammation without compromising the efficacy of photodynamic therapy for actinic keratoses: a randomized clinical trial
Authors: S.R. Wiegell, B. Petersen, H.C. Wulf
Journal: British Journal of Dermatology (2014)

Journal Article Topical corticosteroid reduces inflammation without compromising the efficacy of photodynamic therapy for actinic keratoses: a randomized clinical trial Get access S.R. Wiegell, S.R. Wiegell Department of Dermatology D92 Bispebjerg Hospital Bispebjerg Bakke 23 2400 Copenhagen NV Denmark Correspondence Stine Regin Wiegell. E‐mail: stine.regin.wiegell@regionh.dk Search for other works by this author on: Oxford Academic Google Scholar B. Petersen, B. Petersen Department of Dermatology D92 Bispebjerg Hospital Bispebjerg Bakke 23 2400 Copenhagen NV Denmark Search for other works by this author on: Oxford Academic Google Scholar H.C. Wulf H.C. Wulf Department of Dermatology D92 Bispebjerg Hospital Bispebjerg Bakke 23 2400 Copenhagen NV Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 6, 1 December 2014, Pages 1487–1492, https://doi.org/10.1111/bjd.13284 Published: 01 December 2014
Serum nitrate and nitrite levels in patients with rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis
Authors: Y Ersoy
Journal: Annals of the Rheumatic Diseases (2002)

To assess and compare serum nitrate and nitrite levels in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and osteoarthritis (OA).Thirty five patients with RA, 32 patients with AS, and 36 patients with OA were entered into this study. In addition, 30 healthy volunteers acted as a control group. Concentrations of nitrate and nitrite in serum were determined by direct and indirect Griess reactions. C reactive protein and erythrocyte sedimentation rate levels were determined as markers of systemic activity of disease (SAD) in RA and AS groups.Serum nitrate and nitrite levels were found to be higher in patients with AS and RA than in the OA group (p<0.01). In addition, serum nitrate and nitrite levels were higher in all three groups than in the control group (p<0.01). Moreover, serum nitrate and nitrite levels were higher in patients who had SAD than in those who had not in the RA and AS groups (p<0.01 and p<0.05, respectively), and there was a correlation between serum nitrate and nitrite concentrations and SAD variables in patients with RA (Spearman's r(s)=0.414, p<0.05 and r(s)=0.408, p<0.05, respectively) and AS (r(s)=0.421, p<0.05 and r(s)=0.412, p<0.05, respectively).The findings suggest that nitrate and nitrite production is enhanced in patients with inflammatory arthritis compared with OA. In addition, serum nitrate and nitrite levels are enhanced in patients with RA, AS, and OA compared with healthy subjects. Furthermore, there is a correlation between the SAD variables and serum nitrate and nitrite levels in patients with RA and AS.
Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptor
Authors: Hajime Nishimoto, Seung-Woo Lee, Hong Hong, Karen G. Potter, Mari Maeda-Yamamoto, Tatsuya Kinoshita, Yuko Kawakami, Robert S. Mittler, Byoung S. Kwon, Carl F. Ware, Michael Croft, Toshiaki Kawakami
Journal: Blood (2005)
Dorrell resigns as chairman of health select committee
Authors: A. O'Dowd
Journal: BMJ (2014)

Stephen Dorrell, the former UK health secretary, has resigned from his post as chairman of the parliamentary health select committee, saying that he planned to make a “more effective contribution” to health in a different way.

Dorrell announced what was a surprising resignation on 4 June in a letter to John Bercow, the speaker of the House of Commons. In his resignation letter Dorrell said that he had tried to chair the committee in a way that emphasised the “broad measure of agreement” that he believed existed across party divisions on certain key objectives of health policy. He said that all parties were committed to addressing …
Different lung responses to cigarette smoke in two strains of mice sensitive to oxidants
Authors: B. Bartalesi, E. Cavarra, S. Fineschi, M. Lucattelli, B. Lunghi, P. A. Martorana, G. Lungarella
Journal: European Respiratory Journal (2005)

The development of cigarette smoke-induced pulmonary changes in C57 Bl/6J and DBA/2 mice was investigated. Both strains are sensitive to oxidants and C57Bl/6J mice are moderately deficient in serum alpha1-proteinase inhibitor. Following chronic exposure to cigarette smoke, patchy emphysema was present in mice of both strains, but developed faster in DBA/2 mice. A positive reaction for mouse neutrophil elastase was seen on the septa of both strains. Additionally, the DBA/2 mice developed a uniform parenchymal dilation that was preceded by the appearance of apoptotic cells in areas with a low signal for vascular endothelial growth factor-receptor 2. Fibrotic areas scattered throughout the parenchyma, coupled with a positive immunohistochemical reaction for transforming growth factor-β was seen only in DBA/2 mice. Both DBA/2 and C57Bl/6J strains showed epithelial cell injury and areas of deciliation in their airways. However, the appearance of goblet cell metaplasia was common in C57Bl/6J mice but rare in DBA/2 mice. A positive immunohistochemical reaction for interleukin (IL)-4, IL-13 and MUC5AC was seen only in the airways of C57Bl/6J mice. Strain characteristics (alpha1-proteinase inhibitor levels, sensitivity to oxidants, and constitutive levels of vascular endothelial growth factor-receptor 2) and phenotypical responses (apoptosis and cytokine distribution) may condition parenchymal and airway changes to cigarette smoke.
Smoking-Induced Ventral Striatum Dopamine Release
Authors: Arthur L Brody, Richard E Olmstead, Edythe D London, Judah Farahi, Jeffrey H Meyer, Paul Grossman, Grace S Lee, Joe Huang, Emily L Hahn, Mark A Mandelkern
Journal: American Journal of Psychiatry (2004)

Substantial evidence from animal models demonstrates that dopamine release in the ventral striatum underlies the reinforcing properties of nicotine. The authors used [(11)C]raclopride bolus-plus-continuous-infusion positron emission tomography (PET) to determine smoking-induced ventral striatum dopamine release in humans.Twenty nicotine-dependent smokers (who smoked > or =15 cigarettes/day) underwent a [(11)C]raclopride bolus-plus-continuous-infusion PET session. During the session, subjects had a 10-minute break outside the PET apparatus during which 10 subjects smoked a cigarette and 10 did not smoke (as a control condition).The group that smoked had greater reductions in [(11)C]raclopride binding potential in ventral striatum regions of interest than the group that did not smoke, particularly in the left ventral caudate/nucleus accumbens and left ventral putamen (range for smoking group=-25.9% to -36.6% reduction). Significant correlations were found between change from before to after the smoking break in craving ratings and change from before to after the break in binding potential for these two regions.Nicotine-dependent subjects who smoked during a break in PET scanning had greater reductions in [(11)C]raclopride binding potential (an indirect measure of dopamine release) than nicotine-dependent subjects who did not smoke. The magnitude of binding potential changes was comparable to that found in studies that used similar methods to examine the effects of other addictive drugs.
T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing
Authors: Ko Kudo, Chihaya Imai, Paolo Lorenzini, Takahiro Kamiya, Koji Kono, Andrew M. Davidoff, Wee Joo Chng, Dario Campana
Journal: Cancer Research (2013)

To expand applications for T-cell-based immunotherapy in cancer, we designed a receptor that binds the Fc portion of human immunoglobulins and delivers activation signals. The construct included the high-affinity CD16 (FCGR3A) V158 variant, CD8α hinge, and transmembrane domains, along with signaling domains from CD3ζ and 4-1BB (TNFRSF9), forming a chimeric receptor termed CD16V-BB-ζ. After retrovirus-mediated expression in human T cells, CD16V-BB-ζ bound humanized antibodies with higher affinity than a control receptor containing the more common F158 variant. Engagement of CD16V-BB-ζ provoked T-cell activation, exocytosis of lytic granules, and sustained proliferation, with a mean cell recovery after 4-week coculture with Daudi lymphoma cells and rituximab of nearly 70-fold relative to input cells. In contrast, unbound antibody alone produced no effect. CD16V-BB-ζ T cells specifically killed lymphoma cells and primary chronic lymphocytic leukemia cells in combination with rituximab at a low effector:target ratio, even when assayed on mesenchymal cells. Trastuzumab triggered CD16V-BB-ζ-mediated killing of HER2 (ERBB2)(+) breast and gastric cancer cells; similar results were obtained with an anti-GD2 antibody in neuroblastoma and osteosarcoma cells. Furthermore, coadministration of CD16V-BB-ζ T cells with immunotherapeutic antibodies exerted considerable antitumor activity in vivo. Signaling mediated by 4-1BB-CD3ζ induced higher T-cell activation, proliferation, and cytotoxicity than CD3ζ or FcεRIγ, and the receptor was expressed effectively after mRNA electroporation without viral vectors, facilitating clinical translation. Our results offer preclinical proof of concept for CD16V-BB-ζ as a universal, next-generation chimeric receptor with the potential to augment the efficacy of antibody therapies for cancer.
Targeting Metabolic Changes in Cancer: Novel Therapeutic Approaches
Authors: Ekaterina Bobrovnikova-Marjon, Jonathan B. Hurov
Journal: Annual Review of Medicine (2014)

Therapeutic strategies designed to target cancer metabolism are an area of intense research. Antimetabolites, first used to treat patients in the early twentieth century, served as an early proof of concept for such therapies. We highlight strategies that attempt to improve on the anti-metabolite approach as well as new metabolic drug targets. Some of these targets have the advantage of a strong genetic anchor to drive patient selection (isocitrate dehydrogenase 1/2, Enolase 2). Additional approaches described here derive from hypothesis-driven and systems biology efforts designed to exploit tumor cell metabolic dependencies (fatty acid oxidation, nicotinamide adenine dinucleotide synthesis, glutamine biology).
Portal hypertension in fulminant viral hepatitis.
Authors: D Lebrec, O Nouel, J Bernuau, B Rueff, J P Benhamou
Journal: Gut (1980)

The gradient between wedged and free hepatic venous pressures were measured in 10 unselected adult patients suffering from fulminant viral hepatitis. The gradient was increased in all the studied patients, ranging from 0.9 to 2.1 kPa; this finding indicates that portal hypertension was present in all these cases. Ascites was present in all the five patients having a gradient about 1.5 kPa and affected only two of the five patients having a gradient below 1.5 kPa; this observation suggests that portal hypertension plays a role in the mechanism of ascites in fulminant viral hepatitis. Portal hypertension in fulminant viral hepatitis is likely to be the consequence of an intrahepatic block due to massive necrosis of the liver cells.
Apolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease
Authors: G W Small, J C Mazziotta, M T Collins, L R Baxter, M E Phelps, M A Mandelkern, A Kaplan, A La Rue, C F Adamson, L Chang
Journal: JAMA (1995)

Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD.After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups.University medical center.At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3).Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18.Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4.These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.
Mitochondrial permeability transition pore induces mitochondria injury in Huntington disease
Authors: Rodrigo A Quintanilla, Youngnam N Jin, Rommy von Bernhardi, Gail VW Johnson
Journal: Molecular Neurodegeneration (2013)

Mitochondrial impairment has been implicated in the pathogenesis of Huntington's disease (HD). However, how mutant huntingtin impairs mitochondrial function and thus contributes to HD has not been fully elucidated. In this study, we used striatal cells expressing wild type (STHdhQ7/Q7) or mutant (STHdhQ111/Q111) huntingtin protein, and cortical neurons expressing the exon 1 of the huntingtin protein with physiological or pathological polyglutamine domains, to examine the interrelationship among specific mitochondrial functions. Depolarization induced by KCl resulted in similar changes in calcium levels without compromising mitochondrial function, both in wild type and mutant cells. However, treatment of mutant cells with thapsigargin (a SERCA antagonist that raises cytosolic calcium levels), resulted in a pronounced decrease in mitochondrial calcium uptake, increased production of reactive oxygen species (ROS), mitochondrial depolarization and fragmentation, and cell viability loss. The mitochondrial dysfunction in mutant cells was also observed in cortical neurons expressing exon 1 of the huntingtin protein with 104 Gln residues (Q104-GFP) when they were exposed to calcium stress. In addition, calcium overload induced opening of the mitochondrial permeability transition pore (mPTP) in mutant striatal cells. The mitochondrial impairment observed in mutant cells and cortical neurons expressing Q104-GFP was prevented by pre-treatment with cyclosporine A (CsA) but not by FK506 (an inhibitor of calcineurin), indicating a potential role for mPTP opening in the mitochondrial dysfunction induced by calcium stress in mutant huntingtin cells. Expression of mutant huntingtin alters mitochondrial and cell viability through mPTP opening in striatal cells and cortical neurons.
N-Glycosylation at Two Sites Critically Alters Thiazide Binding and Activity of the Rat Thiazide-sensitive Na+
Authors: Robert S Hoover, Esteban Poch, Adriana Monroy, Norma Vázquez, Toshiyuki Nishio, Gerardo Gamba, Steven C Hebert
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The rat thiazide-sensitive Na-Cl cotransporter (rNCC) is expressed in the renal distal convoluted tubule and is the site of action of an important class of antihypertensive agents, the thiazide diuretics. The amino acid sequence contains two potential <i>N</i>-linked glycosylation consensus sites, N404 and N424. Either enzymatic deglycosylation or tunicamycin reduced the cotransporter to its core molecular weight (113 kD). Glycosylation site single mutants expressed in oocytes ran as thick bands at 115 kD, consistent with the high-mannose glycoprotein. The double mutant produced the single thin 113-kD band seen in the deglycosylated cotransporter. Functional expression of cotransporters in <i>Xenopus laevis</i> oocytes revealed that the mutants displayed drastically decreased thiazide-sensitive <sup>22</sup>Na<sup>+</sup> uptake compared with wild-type NCC. Analysis of enhanced green fluorescence protein (EGFP)–tagged cotransporters demonstrated that this decrease in function is predominantly secondary to decreased surface expression. The elimination of glycosylation in the double mutant increased thiazide sensitivity by more than two orders of magnitude and also increased Cl<sup>−</sup> affinity. Thus, we have demonstrated that rNCC is <i>N</i>-glycosylated <i>in vivo</i> at two sites, that glycosylation is essential for efficient function and surface expression of the cotransporter, and that the elimination of glycosylation allows much greater access of thiazide diuretics to their binding site. E-mail: steven.hebert@yale.edu
Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma
Authors: J.J.C. Verhoeff, C. Lavini, M.E. van Linde, L.J.A. Stalpers, C.B.L.M. Majoie, J.C. Reijneveld, W.R. van Furth, D.J. Richel
Journal: Annals of Oncology (2010)
Use of antenatal corticosteroids and tocolytic drugs in preterm births in 29 countries: an analysis of the WHO Multicountry Survey on Maternal and Newborn Health
Authors: Joshua P Vogel, João Paulo Souza, A Metin Gülmezoglu, Rintaro Mori, Pisake Lumbiganon, Zahida Qureshi, Guillermo Carroli, Malinee Laopaiboon, Bukola Fawole, Togoobaatar Ganchimeg, Jun Zhang, Maria Regina Torloni, Meghan Bohren, Marleen Temmerman
Journal: The Lancet (2014)
Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma
Authors: A Diepstra, M Niens, E Vellenga, GW van Imhoff, IM Nolte, M Schaapveld, G van der Steege, A van den Berg, RE Kibbelaar, GJ te Meerman, S Poppema
Journal: The Lancet (2005)
Salt and water absorption in the human colon: a modern appraisal
Authors: G I SANDLE
Journal: Gut (1998)

The past 20 years have seen many advances in all aspects of colonic physiology, and the unrelenting appearance of new information is daunting to clinicians and scientists alike. Nevertheless, we should not lose sight of the fact that the main function of the human colon is to absorb about 90% of the 1.5–2 litres of ileal effluent which passes daily through the ileocaecal valve.1 2 In mammalian species, the key determinant of colonic water absorption is the rate of Na+ absorption. We now know that Na+ transport processes are not distributed uniformly throughout the human colon, a concept which has important clinical implications. This review provides an update on the basic mechanisms underlying salt and water transport in the human colon in health and disease, and highlights several interesting areas for future research.

The human colon has a nominal mucosal surface area of about 2000 cm2,3 but in reality the total absorptive area is even greater because colonic crypt cells are capable of absorption as well as secretion.4 Although it is well established that the rates of colonic salt (Na+ plus Cl−) and water absorption are directly related,5 it is only recently that we have begun to appreciate the array of Na+absorptive processes present in human colon. These show considerable intrinsic segmental heterogeneity.6-10 This explains, at least in part, why the colon’s capacity for sodium and water absorption in vivo is greater in the proximal (ascending) segment than in the distal (descending and sigmoid colon/rectum) segment.11-15 Several different active (transcellular) Na+ absorptive processes exist in human colon. It will become clear that segmental differences in the distribution and regulation of these processes play an important role in colonic Na+ salvage during periods of salt …
Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification
Authors: Alicia N Minniti, Daniela L Rebolledo, Paula M Grez, Ricardo Fadic, Rebeca Aldunate, Irene Volitakis, Robert A Cherny, Carlos Opazo, Colin Masters, Ashley I Bush, Nibaldo C Inestrosa
Journal: Molecular Neurodegeneration (2009)

The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Abeta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Abeta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Abeta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly.In the present work, we found that intracellular Abeta aggregation in muscle cells of Caenorhabditis elegans overexpressing Abeta peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Abeta. We show that intracellular amyloid aggregation of wild type Abeta is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Abeta-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates.Our data show that intracellular Abeta amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Abeta aggregation may be part of a cell protective mechanism.
The Value of Electrocardiogram Monitoring in Diabetic Ketoacidosis
Authors: John I Malone, Sidney J Brodsky
Journal: Diabetes Care (1980)

Electrolyte abnormalities cause fatal cardiac arrhythmias in patients with diabetic ketoacidosis. A patient is reported with electrocardiogram (ECG) abnormalities characteristic of toxic hyperkalemia and hypocalcemia. The ECG abnormalities were noted during the first hour after arriving at the hospital. The laboratory values confirming the electrolyte abnormalities were not available for more than 1 h after the ECG indicated the danger of myocardial toxicity. During the initial 2 h of therapy the patient was urinating and not in shock. ECG monitoring of this patient prevented the routine administration of intravenous potassium, which was potentially lethal. The clinical importance of electrolyte levels in the management of diabetic ketoacidosis is the prevention of cardiac arrhythmias. ECG monitoring should be a minimal standard in the management of diabetic ketoacidosis.
Mental Illness in Adults With Fetal Alcohol Syndrome or Fetal Alcohol Effects
Authors: C Famy, A P Streissguth, A S Unis
Journal: American Journal of Psychiatry (1998)

The authors' goal was to use structured clinical interviews to characterize the type and frequency of mental illness in adults with fetal alcohol syndrome or fetal alcohol effects.Twenty-five subjects who met criteria for fetal alcohol syndrome or fetal alcohol effects, who were older than 18 years old, and who had an IQ of greater than 70 were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders and the Structured Clinical Interview for DSM-III-R Personality Disorders.Eighteen of the 25 subjects had received psychiatric treatment. The most common axis I disorders were alcohol or drug dependence (15 subjects), depression (11 subjects), and psychotic disorders (10 subjects). The most common axis II disorders were avoidant (six subjects), antisocial (four subjects), and dependent (three subjects) personality disorders.This study suggests that adults with fetal alcohol syndrome or fetal alcohol effects suffer from substantial mental illness.