tbuckley/cabot-search huggingface dataset:
Rheumatoid arthritis susceptibility genes associate with lipid levels in patients with rheumatoid arthritis
Authors: Tracey E Toms, Vasileios F Panoulas, Jacqueline P Smith, Karen M J Douglas, Giorgos S Metsios, Antonios Stavropoulos-Kalinoglou, George D Kitas
Journal: Annals of the Rheumatic Diseases (2011)

Rheumatoid arthritis (RA), a systemic inflammatory disease with complex genetic aetiology, associates with excess cardiovascular morbidity and mortality. Dyslipidaemia, a major cardiovascular risk factor has been reported to predate the onset of RA, thus suggesting a potential genetic link between the two conditions. The authors assessed whether RA susceptibility genes associate with the presence of dyslipidaemia in RA patients.400 well-characterised RA patients were included in this cross-sectional study. Fasting lipid profile (total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, apolipoproteins (ApoA and ApoB) and lipoprotein (a)) and four RA susceptibility genes (PTPN22, TRAF1/C5, STAT4 and human leucocyte antigen shared epitope (HLA-SE)) were assessed and associations were sought in both univariate and multivariate analyses.Following adjustment for age, sex and erythrocyte sedimentation rate, the G allele of TRAF1/C5 associated with lower total cholesterol (p=0.010), LDL (p=0.022) and ApoB (p=0.014); one or more copies of the shared epitope associated with lower ApoA (p=0.035) and higher ApoB:ApoA ratio (p=0.047); while STAT4 TT homozygotes had higher lipoprotein (a) (p=0.004).RA susceptibility genes (TRAF1/C5, STAT4 and HLA-DRB1-SE) may be involved in the regulation of lipid metabolism in RA patients, thus contributing to cardiovascular disease (CVD) risk and adverse outcome. If these findings are replicated, such genotyping could be used to identify and target for prevention those RA patients most at risk of CVD. It will also be interesting to study the association of these genes with lipid levels in the general population and identify mechanisms to explain the link.
Point Mutation at Single Tyrosine Residue of Novel Oncogene NOK Abrogates Tumorigenesis in Nude Mice
Authors: Yue Chen, Ying-Hua Li, Xi-Ping Chen, Li-Min Gong, Shu-Ping Zhang, Zhi-Jie Chang, Xiu-Fang Zhang, Xin-Yuan Fu, Li Liu
Journal: Cancer Research (2005)

Abstract Receptor protein-tyrosine kinases (RPTKs) are tightly regulated during normal cellular processes including cell growth, differentiation, and metabolism. Recently, a RPTK-like molecule named novel oncogene with kinase-domain (NOK) has been cloned and characterized. Overexpression of NOK caused severe cellular transformation as well as tumorigenesis and metastasis in nude mice. In the current study, we generated two tyrosine→phenylalanine (Y→F) point mutations (Y327F and Y356F) within the endodomain of NOK that are well conserved in many RPTK subfamilies and are the potential tyrosine phosphorylation sites important for major intracellular signaling. Using BaF3 cells stably expressing the ectodomain of mouse erythropoietin receptor, and the transmembrane and endodomain of NOK (BaF3-E/N), we were able to show that point mutations at either Y327 or Y356 dramatically blocked cellular transformation by NOK as examined by colony formation and cellular DNA synthesis. In addition, tumorigenesis induced by BaF3-E/N was completely abrogated upon the introduction of either single mutation. Importantly, signaling studies revealed that the activation of extracellular signal-regulated kinase was inhibited by Y356F and was significantly reduced by Y327F. Both mutations significantly impaired Akt phosphorylation. Interestingly, both mutations did not affect the kinase activity of NOK. Moreover, apoptotic analysis revealed that both mutations accelerated cell death by activating caspase-3–mediated pathways. Thus, our study shows that these potential tyrosine phosphorylation sites may play critical roles in NOK-mediated tumorigenesis both in vitro and in vivo.
Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial
Authors: M Bocchia, S Gentili, E Abruzzese, A Fanelli, F Iuliano, A Tabilio, M Amabile, F Forconi, A Gozzetti, D Raspadori, S Amadori, F Lauria
Journal: The Lancet (2005)
Effects of algorithm for diagnosis of active labour: cluster randomised trial
Authors: H. Cheyne, V. Hundley, D. Dowding, J M. Bland, P. McNamee, I. Greer, M. Styles, C. A Barnett, G. Scotland, C. Niven
Journal: BMJ (2008)

The COVID-19 outbreak is on the world. While many countries have imposed general lockdown, emergency services are continuing. Healthcare professionals have been infected with the virulent severe acute respiratory syndrome coronavirus-2 (SARS), which spreads by close contact and aerosols. The anesthesiologist is particularly vulnerable to aerosols while performing intubation and other airway related procedures. Regional anesthesia (RA) minimizes the need for airway manipulation and the risks of cross infection to other patients, and the healthcare personnel. In this context, for prioritizing RA over general anesthesia, wherever possible, a structured algorithmic approach is outlined. The role of percentage saturation of hemoglobin with oxygen (oxygen saturation), blood pressure and early use of point-of-care ultrasound in differential diagnosis and specific management is detailed. The perioperative anesthetic implications of multisystem manifestations of COVID-19, anesthetic management options, the scope of RA and considerations for its safe conduct in operating rooms is described. An outline for safe and rapid training of healthcare personnel, with an Entrustable Professional Activity framework for ascertaining the practice readiness among trained residents for RA in COVID-19, is suggested. These are the authors’ experiences gained from the current pandemic and similar SARS, Middle East Respiratory Syndrome and influenza outbreaks in recent past faced by our authors in Singapore, India, Hong Kong and Canada.
International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli
Authors: Sadashiva S. Karnik, Hamiyet Unal, Jacqueline R. Kemp, Kalyan C. Tirupula, Satoru Eguchi, Patrick M. L. Vanderheyden, Walter G. Thomas
Journal: Pharmacological Reviews (2015)

The renin angiotensin system (RAS) produced hormone peptides regulate many vital body functions. Dysfunctional signaling by receptors for RAS peptides leads to pathologic states. Nearly half of humanity today would likely benefit from modern drugs targeting these receptors. The receptors for RAS peptides consist of three G-protein–coupled receptors—the angiotensin II type 1 receptor (AT<sub>1</sub> receptor), the angiotensin II type 2 receptor (AT<sub>2</sub> receptor), the MAS receptor—and a type II trans-membrane zinc protein—the candidate angiotensin IV receptor (AngIV binding site). The prorenin receptor is a relatively new contender for consideration, but is not included here because the role of prorenin receptor as an independent endocrine mediator is presently unclear. The full spectrum of biologic characteristics of these receptors is still evolving, but there is evidence establishing unique roles of each receptor in cardiovascular, hemodynamic, neurologic, renal, and endothelial functions, as well as in cell proliferation, survival, matrix-cell interaction, and inflammation. Therapeutic agents targeted to these receptors are either in active use in clinical intervention of major common diseases or under evaluation for repurposing in many other disorders. Broad-spectrum influence these receptors produce in complex pathophysiological context in our body highlights their role as precise interpreters of distinctive angiotensinergic peptide cues. This review article summarizes findings published in the last 15 years on the structure, pharmacology, signaling, physiology, and disease states related to angiotensin receptors. We also discuss the challenges the pharmacologist presently faces in formally accepting newer members as established angiotensin receptors and emphasize necessary future developments.
Double Induction Containing Either Two Courses or One Course of High-Dose Cytarabine Plus Mitoxantrone and Postremission Therapy by Either Autologous Stem-Cell Transplantation or by Prolonged Maintenance for Acute Myeloid Leukemia
Authors: Thomas Büchner, Wolfgang E. Berdel, Claudia Schoch, Torsten Haferlach, Hubert L. Serve, Joachim Kienast, Susanne Schnittger, Wolfgang Kern, Joelle Tchinda, Albrecht Reichle, Eva Lengfelder, Peter Staib, Wolf-Dieter Ludwig, Carlo Aul, Hartmut Eimermacher, Leopold Balleisen, Maria-Cristina Sauerland, Achim Heinecke, Bernhard Wörmann, Wolfgang Hiddemann
Journal: Journal of Clinical Oncology (2006)

Intensification by high-dose cytarabine in postremission or induction therapy and prolonged maintenance are established strategies to improve the outcome in patients with acute myeloid leukemia (AML). Whether additional intensification can add to this effect has not yet been determined.A total of 1,770 patients (age 16 to 85 years) with de novo or secondary AML or high-risk myelodysplastic syndrome (MDS) were randomly assigned upfront for induction therapy containing one course with standard dose and one course with high-dose cytarabine, or two courses with high-dose cytarabine, and in the same step received postremission prolonged maintenance or busulfan/cyclophosphamide chemotherapy with autologous stem-cell transplantation.The complete remission rate in patients younger than 60 and > or = 60 years of age was 70% and 53%, respectively. The overall survival at 3 years in the two age groups was 42% and 19%, the relapse-free survival was 40% and 19%, and the ongoing remission duration was 48% and 22%, respectively. There were no significant differences in these results between the two randomized induction arms or between the two postremission therapy arms. There was no significant difference in any prognostic subgroup according to secondary AML/MDS, cytogenetics, WBC, lactate dehydrogenase, and early blast clearance.The regimen of one course with standard-dose cytarabine and one course with high-dose cytarabine for induction, and prolonged maintenance for postremission chemotherapy in patients with AML is not improved by additional escalation in cytotoxic treatment.
Selective A2-adenosine receptor agonists do not alter action potential duration, twitch shortening, or cAMP accumulation in guinea pig, rat, or rabbit isolated ventricular myocytes.
Authors: J Shryock, Y Song, D Wang, S P Baker, R A Olsson, L Belardinelli
Journal: Circulation Research (1993)

In this study, the hypothesis that mammalian ventricular myocytes possess A2-adenosine receptors was tested. Electrophysiological, contractile, and cAMP responses to the selective A2-adenosine receptor agonists 2-[2-(4-methylphenyl)ethoxy]adenosine (WRC-0090) and 2-(2-cyclohexylethoxy)adenosine (WRC-0013) and the nonselective adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA) were measured using ventricular myocytes isolated from guinea pig, rabbit, and rat hearts. Pertussis toxin pretreatment and/or the selective A1-adenosine receptor antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and (+/-)N6-endonorbornan-2-yl-9-methyladenine (N-0861) were used to prevent activation of A1-adenosine receptors in these cells. Action potential duration at 50% repolarization was not altered by WRC-0090, NECA, or WRC-0013 with or without 0.1 microM DPCPX or pertussis toxin pretreatment, and WRC-0090 and NECA failed to prolong the action potential duration of myocytes exposed to 0.1 or 1 microM forskolin. WRC-0090 alone or with 0.1 microM DPCPX did not increase the amplitude of shortening of pertussis toxin-treated or untreated myocytes, and WRC-0090 or NECA did not significantly increase cAMP accumulation. In contrast to these results with myocytes, in the smooth muscle cell line DDT1MF-2 the effect of both selective A2-agonists on cAMP accumulation was biphasic: low concentrations (&lt; or = 0.3 microM) increased but higher concentrations decreased accumulation of cAMP. The decreased cAMP accumulation seen at higher agonist concentrations was completely abolished by either 0.1 microM DPCPX or pretreatment of cells with pertussis toxin. In summary, the results of the present study do not provide evidence for A2-adenosine receptors on mammalian ventricular cardiomyocytes but confirm reports of the coexistence of both A1 and A2 subtypes of adenosine receptors on DDT1MF-2 cells.
Selective Depletion of Foxp3+ Regulatory T Cells Improves Effective Therapeutic Vaccination against Established Melanoma
Authors: Katjana Klages, Christian T. Mayer, Katharina Lahl, Christoph Loddenkemper, Michele W.L. Teng, Shin Foong Ngiow, Mark J. Smyth, Alf Hamann, Jochen Huehn, Tim Sparwasser
Journal: Cancer Research (2010)

Abstract Tumor-bearing individuals have been reported to harbor increased numbers of Foxp3+ regulatory T cells (Treg), which prevent the development of efficient antitumor immune responses. Thus, Treg depletion has already been tested as a promising therapeutic approach in various animal models and entered clinical trials. However, the use of nonspecific Treg targeting agents such as CD25 depleting antibodies, which in addition to CD25+ Tregs also deplete recently activated CD25+ effector T cells, potentially masked the tremendous potential of this therapeutic strategy. To avoid such nonspecific effects, we used transgenic DEREG (depletion of regulatory T cells) mice, which express a diphtheria toxin receptor under control of the Foxp3 locus, allowing selective depletion of Foxp3+ Tregs even during ongoing immune responses. We showed that Foxp3+ Treg depletion induced partial regression of established ovalbumin (OVA)-expressing B16 melanoma, which was associated with an increased intratumoral accumulation of activated CD8+ cytotoxic T cells. The antitumor effect could be significantly enhanced when Treg depletion was combined with vaccination against OVA. To further assess whether this therapeutic approach would break self-tolerance, we crossed DEREG mice with RipOVAlow mice, expressing OVA as neo–self-antigen under control of the rat insulin promoter. In these mice, combined Treg depletion and vaccination also induced tumor regression without the onset of diabetes. Together, our data suggest that selective Treg targeting strategies combined with vaccinations against tumor-associated (self) antigens have the potential to evoke efficient antitumor responses without inducing overt autoimmunity. These findings might have implications for future therapeutic interventions in cancer patients. Cancer Res; 70(20); 7788–99. ©2010 AACR.
Forced oscillation technique (FOT) in relation to exercise-induced dyspnea without FEV1-fall - Results from ANDAS-study
Authors: Henrik Johansson, Pasquale Pio Pompilio, Katarina Norlander, Raffaele Dellacá, Andrei Malinovschi
Journal: European Respiratory Journal (2013)

A significant proportion of children without asthma diagnosis reports exercise-induced dyspnea. A poor agreement is reported between exercise-induced dyspnea and FEV1-fall. Therefore we assessed if FOT might be useful to identify airways obstruction in children with exercise-induced dyspnea without significant FEV1-fall (  A postal questionnaire on dyspnea after strenuous exercise was answered by 2309 children aged 13-14 years. A sample of subjects with symptoms were invited in a ratio of 2:1 (to subjects w/o symptoms) for an exercise provocation test with pre- and post-exercise assessment of FEV1 as well as inspiratory resistance at 5 Hz (R5) and frequency dependence of resistance (R5-19) by FOT. Healthy subjects (group A, n=9, median FEV1 96.0%pred), subjects with exercise-induced dyspnea, but no FEV1-fall (group B, n=10, FEV1 88.0%pred) and subjects with dyspnea and FEV1-fall (group C, n=9, FEV1 89.5%pred) were studied.  The median (range) FEV1-fall was 4.3% (-1, 9.1) in group A, 4.3% (-0.5, 6.4) in group B and 20.4% (12.6, 38.3) in group C. No significant changes of R5 or R5-19 were found post-exercise in group A. R5 and R5-19 (mean±SEM, cmH2O*s*L-1) increased in group B at 7 min post-exercise (3.37±0.17 vs 3.07±0.19 at baseline, p=0.003 and 0.43±0.10 vs 0.09±0.06, p  In conclusion, FOT measurements might identify changes in airway caliber and lung mechanics in children with exercise-induced dyspnea without FEV1-fall. The clinical importance of these findings warrants further studies.
Analysis of Cardiovascular Phenotype and Genotype-Phenotype Correlation in Individuals With a <i>JAG1</i> Mutation and/or Alagille Syndrome
Authors: Doff B. McElhinney, Ian D. Krantz, Lynn Bason, David A. Piccoli, Karan M. Emerick, Nancy B. Spinner, Elizabeth Goldmuntz
Journal: Circulation (2002)

Background— Cardiovascular anomalies are among the most common features of Alagille syndrome (AGS). Mutations of JAG1 are found in most individuals with AGS. This study was undertaken to determine the spectrum of cardiovascular phenotypes associated with a JAG1 mutation and/or AGS, investigate potential genotype-phenotype correlations, and begin to correlate clinical outcome with genetic pathogenesis. Methods and Results— We reviewed the records of 200 individuals with a JAG1 mutation or AGS. A total of 187 (94%) subjects had evidence of cardiovascular involvement. Cardiovascular anomalies were identified by imaging in 150 subjects (75%), and 37 (19%) had a peripheral pulmonary stenosis murmur with either a normal echocardiogram or no imaging study. Of the 150 subjects with anomalies confirmed by imaging, right-sided anomalies were present in 123 and left-sided anomalies in 22, with both in 12. Seventeen subjects had other anomalies. The most common abnormality was stenosis/hypoplasia of the branch pulmonary arteries (PAs), which was documented by imaging (n=111) or inferred from a peripheral pulmonary stenosis murmur (n=41) in 76% of subjects. Tetralogy of Fallot was present in 23 subjects and was accompanied by pulmonary atresia in 8. Branch PA phenotype differed between individuals with and without a JAG1 mutation. Among subjects with a JAG1 mutation, there was no correlation between the type or location of mutation and the frequency or type of cardiovascular anomaly. Conclusions— More than 90% of individuals with a JAG1 mutation or AGS have cardiovascular anomalies, with branch PA stenosis the most common abnormality. Cardiovascular phenotype does not correlate with the type or location of JAG1 mutation.
Reactive oxygen species and antioxidant defense in puromycin aminonucleoside glomerulopathy.
Authors: W Gwinner, U Landmesser, R P Brandes, B Kubat, J Plasger, O Eberhard, K M Koch, C J Olbricht
Journal: Journal of the American Society of Nephrology (1997)

Results from several radical scavenger studies indirectly suggested an involvement of reactive oxygen species in the pathogenesis of puromycin aminonucleoside glomerulopathy. In this study, generation of reactive oxygen species was examined directly in glomeruli isolated from rats in the acute phase of puromycin aminonucleoside nephrosis and related to the changes in the glomerular antioxidant defense. Five and nine days after puromycin aminonucleoside injection, gross proteinuria, reduced creatinine clearances, and typical changes of glomerular morphology were present. Levels of reactive oxygen species were increased eightfold in glomeruli isolated 15 min after puromycin aminonucleoside injection, returned to baseline levels on days 1 and 5 after injection, and rose again to 14-fold on day 9 after injection, as determined by chemiluminescence with luminol. Further analysis of increased glomerular radical generation, using the chemiluminescence enhancer lucigenin and different radical scavengers, suggested a predominant involvement of hydroxyl radical and hydrogen peroxide in the initial increase in reactive oxygen species 15 min after puromycin aminonucleoside. Nine days after induction of nephrosis, primarily superoxide anion and hydroxyl radical were found to contribute to increased reactive oxygen species. Despite oxidative stress, antioxidant enzymes were not induced in the course of nephrosis. On the contrary, catalase and glutathione peroxidase activities declined 9 d after puromycin aminonucleoside injection. The results indicate that a transient increase in glomerular reactive oxygen species is sufficient to induce the oxidative glomerular injury observed in this model and that the glomerulus may not necessarily respond to oxidative stress with an induction of antioxidant enzymes.
Iliac Artery Stress Test
Authors: L.R. Goldberg, G.A. Stouffer
Journal: Circulation (2004)

Angiography and pressure gradient analysis was performed before (A) and after (B) iliac stenting.A demonstrates aortography in antero-posterior and selective iliac angiography in left anterior oblique projections.Simultaneous pressure measurements obtained from the aorta and right common femoral artery under basal conditions and after administration of 400 g of intra-arterial nitroglycerin (NTG) are also shown.B demonstrates selective iliac angiography in an antero-posterior projection after stent placement and simultaneous pressure measurements after administration of 400 g of intra-arterial nitroglycerin.
Zinc deficiency with transitory acrodermatitis enteropathica in a boy of low birth weight
Authors: INGA BLOM, STEN JAMESON, FREDRIK KROOK, BIRGITTA LARSSON-STYMNE, LARS WRANNE
Journal: British Journal of Dermatology (1981)

Journal Article Zinc deficiency with transitory acrodermatitis enteropathica in a boy of low birth weight Get access INGA BLOM, INGA BLOM Departments of Dermatology, Medicine and Pediatrics, Regional Hospital, S‐701 85 Örebro, Sweden Search for other works by this author on: Oxford Academic Google Scholar STEN JAMESON, STEN JAMESON Departments of Dermatology, Medicine and Pediatrics, Regional Hospital, S‐701 85 Örebro, Sweden Search for other works by this author on: Oxford Academic Google Scholar FREDRIK KROOK, FREDRIK KROOK Departments of Dermatology, Medicine and Pediatrics, Regional Hospital, S‐701 85 Örebro, Sweden Search for other works by this author on: Oxford Academic Google Scholar BIRGITTA LARSSON‐STYMNE, BIRGITTA LARSSON‐STYMNE Departments of Dermatology, Medicine and Pediatrics, Regional Hospital, S‐701 85 Örebro, Sweden Search for other works by this author on: Oxford Academic Google Scholar LARS WRANNE LARS WRANNE Departments of Dermatology, Medicine and Pediatrics, Regional Hospital, S‐701 85 Örebro, Sweden Lars Wranne, M.D., Head of the Department of Pediatrics, Regional Hospital, S‐701 85 Örebro, Sweden. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 4, 1 April 1981, Pages 459–464, https://doi.org/10.1111/j.1365-2133.1981.tb15318.x Published: 01 April 1981 Article history Accepted: 06 June 1980 Published: 01 April 1981