tbuckley/cabot-search huggingface dataset:
Vascular Thrombin Receptor Regulation in Hypertensive Rats
Authors: Quinn Capers, Jørn Bech Laursen, Toshiki Fukui, Sanjay Rajagopalan, Ichiro Mori, Pingping Lou, Bruce A. Freeman, William R. Berrington, Kathy K. Griendling, David G. Harrison, Marschall S. Runge, R. Wayne Alexander, W. Robert Taylor
Journal: Circulation Research (1997)

Abstract Thrombin has been implicated as an important mediator of vascular lesion formation in atherosclerosis and restenosis. To investigate a potential role for thrombin signaling in the vascular response to hypertension, we have studied thrombin receptor (TR) expression and regulation in hypertensive rats. Aortic TR mRNA was upregulated by angiotensin II (Ang II)–induced hypertension (10.7±2.5 times control, P &lt;.02), which correlated with a 4-fold increase in thrombin-induced constriction in isolated endothelium-denuded aortic rings. The AT 1 receptor antagonist losartan normalized blood pressure and TR mRNA. Conversely, lowering blood pressure to the same degree with hydralazine did not abolish the upregulation of TR mRNA expression. When low-renin low–Ang II hypertension was induced in Dahl salt-sensitive rats, there was no detectable increase in the expression of aortic thrombin receptor mRNA. Finally, treatment with a chimeric heparin-binding form of the recombinant human Cu/Zn superoxide dismutase caused complete inhibition of TR mRNA upregulation, suggesting that an increased rate of superoxide anion production is an important signaling mechanism. Thus, increased TR expression via a redox-sensitive mechanism in the aortic smooth muscle of rats treated with Ang II represents a novel in vivo mechanism through which the hypertensive effects of Ang II are mediated.
Electrocardiography and Doppler echocardiography for risk stratification in patients with chronic heart failure
Authors: Christian Bruch, Michael Gotzmann, Jörg Stypmann, Frauke Wenzelburger, Markus Rothenburger, Matthias Grude, Hans H. Scheld, Lars Eckardt, Günter Breithardt, Thomas Wichter
Journal: Journal of the American College of Cardiology (2005)
Leukaemoid reaction and ulcerative colitis.
Authors: P Merrin, M J Lancaster Smith
Journal: Gut (1989)

We describe a patient who presented with a pronounced neutrophil leucocytosis and leukaemoid reaction in association with toxic dilatation of the colon secondary to ulcerative colitis. Although the patient had been previously investigated, the significance of bowel disturbance had not been recognised. Once the inflammatory bowel disease was treated the haematological abnormality subsided.
Type 2 Diabetes and Intravenous Thrombolysis Outcome in the Setting of ST Elevation Myocardial Infarction
Authors: Michael N. Zairis, Anastassios G. Lyras, Stamatis S. Makrygiannis, Paraskevi K. Psarogianni, Evdokia N. Adamopoulou, Stelios M. Handanis, Apostolos Papantonakos, Spyros K. Argyrakis, Athanasios A. Prekates, Stefanos G. Foussas
Journal: Diabetes Care (2004)

There are conflicting results regarding the impact of type 2 diabetes on intravenous thrombolysis effectiveness during ST elevation myocardial infarction (STEMI). The present study, using a continuous 12-lead electrocardiogram, examined the possible association of type 2 diabetes with both acute intravenous thrombolysis effectiveness and long-term prognosis in this setting.The study included 726 consecutive subjects (214 type 2 diabetic subjects) with STEMI who received intravenous thrombolysis in the first 6 h from index pain and were followed up for 3.5 years.Type 2 diabetic subjects had significantly lower incidence of sustained > or = 50% ST recovery than nondiabetic subjects (P = 0.03). Additionally, the former required a significantly greater time interval through the achievement of this criterion than the latter (P < 0.001). In both type 2 diabetic (P < 0.001) and nondiabetic subjects (P < 0.001), those who had not attained > or = 50% ST recovery were at significantly higher risk of cardiac death than subjects who had reached this criterion. The subjects who attained the above electrocardiographic criterion in > or = 60 min after thrombolysis initiation were at significantly higher risk compared with those who achieved this criterion in <60 min (P = 0.02). However, this association was true only for type 2 diabetic subjects (P = 0.01) and not for nondiabetic subjects (P = 0.9).The present study suggests that type 2 diabetes is a strong predictor of acute intravenous thrombolysis failure during STEMI. This finding may significantly contribute to the worse prognosis for type 2 diabetic subjects compared with nondiabetic ones in this setting.
Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.
Authors: A D Millar, D S Rampton, C L Chander, A W Claxson, S Blades, A Coumbe, J Panetta, C J Morris, D R Blake
Journal: Gut (1996)

Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease.To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease.Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease.The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n = 5, p = 0.009) and 88% (n = 5, p = 0.03), respectively.The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.
SURFACE ANTIGENS OF IMMUNOCOMPETENT CELLS
Authors: J. J. Mond, T. Takahashi, G. J. Thorbecke
Journal: The Journal of Experimental Medicine (1972)

The effect of preincubation with anti-theta or anti-mouse immunoglobulin (Ig) and complement (C') on immune responsiveness of spleen cells from BALB/c mice immunized with sheep erythrocytes (SE) was investigated. Both treatments greatly depressed the remaining ability to produce a secondary response to SE in vitro. Normal BALB/c spleen cells were far less effective in reconstituting the responses of such depleted cell populations than were much smaller numbers of untreated immune spleen cells. Thymus-derived cell (T cell) memory appeared early after immunization and showed specificity for the immunizing antigens. Recombination of anti-Ig-treated with anti-theta-treated immune spleen cells resulted in virtually complete reconstitution of responsiveness. The presence of immunological memory in T cells and the nature of their surface receptors are discussed.
A Multicenter Tractography Study of Deep White Matter Tracts in Bipolar I Disorder
Authors: Samuel Sarrazin, Cyril Poupon, Julia Linke, Michèle Wessa, Mary Phillips, Marine Delavest, Amelia Versace, Jorge Almeida, Pamela Guevara, Delphine Duclap, Edouard Duchesnay, Jean-François Mangin, Katia Le Dudal, Claire Daban, Nora Hamdani, Marc-Antoine D’Albis, Marion Leboyer, Josselin Houenou
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Tractography studies investigating white matter (WM) abnormalities in patients with bipolar disorder have yielded heterogeneous results owing to small sample sizes. The small size limits their generalizability, a critical issue for neuroimaging studies of biomarkers of bipolar I disorder (BPI). <h3>Objectives</h3> To study WM abnormalities using whole-brain tractography in a large international multicenter sample of BPI patients and to compare these alterations between patients with or without a history of psychotic features during mood episodes. <h3>Design, Setting, and Participants</h3> A cross-sectional, multicenter, international, Q-ball imaging tractography study comparing 118 BPI patients and 86 healthy control individuals. In addition, among the patient group, we compared those with and without a history of psychotic features. University hospitals in France, Germany, and the United States contributed participants. <h3>Interventions</h3> Participants underwent assessment using the Diagnostic Interview for Genetic Studies at the French sites or the Structured Clinical Interview for<i>DSM-IV</i>at the German and US sites. Diffusion-weighted magnetic resonance images were acquired using the same acquisition parameters and scanning hardware at each site. We reconstructed 22 known deep WM tracts using Q-ball imaging tractography and an automatized segmentation technique. <h3>Main Outcomes and Measures</h3> Generalized fractional anisotropy values along each reconstructed WM tract. <h3>Results</h3> Compared with controls, BPI patients had significant reductions in mean generalized fractional anisotropy values along the body and the splenium of the corpus callosum, the left cingulum, and the anterior part of the left arcuate fasciculus when controlling for age, sex, and acquisition site (corrected for multiple testing). Patients with a history of psychotic features had a lower mean generalized fractional anisotropy value than those without along the body of the corpus callosum (corrected for multiple testing). <h3>Conclusions and Relevance</h3> In this multicenter sample, BPI patients had reduced WM integrity in interhemispheric, limbic, and arcuate WM tracts. Interhemispheric pathways are more disrupted in patients with than in those without psychotic symptoms. Together these results highlight the existence of an anatomic disconnectivity in BPI and further underscore a role for interhemispheric disconnectivity in the pathophysiological features of psychosis in BPI.
Abstract 18363: ApoA-I Suppresses Neointimal Hyperplasia Following Stent Deployment and Modulates Neointimal Cellular Phenotype
Authors: Laura Vanags, Joanne Tan, Steven Wise, Ziad Ali, Christina Bursill
Journal: Circulation (2014)

Background: Increases in smooth muscle cell (SMC) cholesterol content reduce the expression of SMC phenotypic markers and increase macrophage related markers. The balance of neointimal SMCs to macrophage-like cells may influence neointimal hyperplasia following stent deployment. Apolipoprotein (apo) A-I, the main protein component of high-density lipoproteins (HDL), mediates the efflux of cholesterol from cells via the cholesterol transporter ABCA1. In a murine model of balloon angioplasty and stenting, we aimed to investigate the effect of apoA-I on neointimal hyperplasia and neointimal cellular phenotype. Methods and Results: Thoracic aortic segments from apoE knockout mice underwent balloon angioplasty alone or balloon angioplasty with stenting then were carotid-interposition grafted into recipient mice. Mice received PBS or apoA-I (40mg/kg) injections on alternate days in the week prior to surgery and then until sacrifice (28 days). There were no changes in total cholesterol, LDL and HDL between groups at sacrifice and thrombosis rates were 16.7% lower in apoA-I injected mice. Histological analysis revealed that stented aortic sections from mice injected with apoA-I had significantly smaller neointimal areas (18%±6.9), compared to PBS control mice p&lt;0.05. The percentage of SMC alpha-actin positive staining was strikingly higher in the neointimas of apoA-I stented arteries (76%±34.3, p&lt;0.05), while RT-PCR analysis of balloon angioplasty injured aortas found mRNA levels of macrophage marker CD68 were lower in apoA-I infused mice (30%±8.9, p&lt;0.01). Furthermore, mRNA levels of ABCA1 and the cholesterol efflux regulator PPAR-gamma were significantly higher in apoA-I balloon-injured aortic segments (30%±13.8 and 48%±20.7, respectively), p&lt;0.05. Conclusion: ApoA-I infusions reduce neointimal area following stent deployment. In apoA-I infused mice, the cells of the neointima had significantly higher SMC alpha-actin expression and lower macrophage CD68 expression. Mechanistically, this may be due to increased SMC cholesterol efflux as apoA-I increased the expression of ABCA1 and PPAR-gamma. These findings have significant implications for therapeutic modulation of neointimal hyperplasia following stent deployment.
Alteration in the Recommended Dosing Schedule for Risperidone
Authors: D J Luchins, D Klass, P Hanrahan, R Malan, J Harris
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors' goal was to study the recommended dose schedule for risperidone. METHOD: They obtained computerized pharmacy data on 1,283 inpatients with the diagnoses of schizophrenia or schizoaffective disorder who were treated with risperidone. Continuance on risperidone was defined as remaining on the drug for 16 days or until discharge. RESULTS: The majority of the patients (84%) continued on risperidone. Use of the recommended dose schedule decreased greatly over time. Patients were more likely to continue on risperidone if they had a higher maximum dose (5.7 mg/day versus 4.7 mg/day), a longer number of days to maximum dose (5.7 days versus 3.9 days), and a maximum rise in dose of 0.5–2 mg/day. CONCLUSIONS: These findings suggest that the recommended dose schedule should be altered to one that recommends a less rapid titration (over 6 days to a week) and that the dose increments consist of 0.5–2 mg/day.
Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer
Authors: Sampurna Chatterjee, Lukas C. Heukamp, Maike Siobal, Jakob Schöttle, Caroline Wieczorek, Martin Peifer, Davide Frasca, Mirjam Koker, Katharina König, Lydia Meder, Daniel Rauh, Reinhard Buettner, Jürgen Wolf, Rolf A. Brekken, Bernd Neumaier, Gerhard Christofori, Roman K. Thomas, Roland T. Ullrich
Journal: Journal of Clinical Investigation (2013)

The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors and initiate the angiogenic switch in tumors remain poorly defined. By combining chemical genetics with multimodal imaging, we have identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal. Disruption of this feed-forward loop by chemical perturbation or knockdown of VEGFR2 in tumor cells dramatically inhibited production of VEGF in vitro and in vivo. This disruption was sufficient to prevent tumor growth in vivo. In patients with lung cancer, we found that this VEGF:VEGFR2 feed-forward loop was active, as the level of VEGF/VEGFR2 binding in tumor cells was highly correlated to tumor angiogenesis. We further demonstrated that inhibition of tumor cell VEGFR2 induces feedback activation of the IRS/MAPK signaling cascade. Most strikingly, combined pharmacological inhibition of VEGFR2 (ZD6474) and MEK (PD0325901) in tumor cells resulted in dramatic tumor shrinkage, whereas monotherapy only modestly slowed tumor growth. Thus, a tumor cell-autonomous VEGF:VEGFR2 feed-forward loop provides signal amplification required for the establishment of fully angiogenic tumors in lung cancer. Interrupting this feed-forward loop switches tumor cells from an angiogenic to a proliferative phenotype that sensitizes tumor cells to MAPK inhibition.
A ‘D.I.Y.’ nasal plug with airway: an alternative approach
Authors: W. Hussain, N.J. Mortimer, C. Gleeson, P.J. Salmon
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, We read with great interest the recent article by Flohr et al.1 describing the use of Merocel® nasal packing with airway as a means of maximizing the contact of skin grafts to the wound bed postoperatively on the nasal tip and ala. The authors are in our opinion, absolutely correct in their assertion that the use of a dental roll for nasal packing is uncomfortable for patients by virtue of the fact that airflow into the nostril is restricted. In an endeavour to make the experience of ‘nasal packing’ as comfortable as possible for our patients, we have for some time been creating our own version of a ‘nasal plug with an airway’ using materials readily available and generally present on the surgical tray. Our technique is illustrated in Figure 1. Local anaesthetic is routinely administered to our patients via a 30‐gauge needle (Fig. 1a). If surgery involves the nasal tip and/or ala, the sterile needle cap is kept on the theatre tray, bathing in antiseptic surgical solution for later use.
Desferrioxamine in acute iron poisoning
Authors: Michael Shannon, Veronika Macarol, ShantaramJ. Yawalkar, K.W. Chan, M. Bond, W. Fernandez, K.J. Anderson, R.P.A. Rivers, Lawrence Helson, Christians Helson, Susan Braverman, Giovanni Deb, Alberto Donfrancesco
Journal: The Lancet (1992)
Conscientious refusal to assist with abortion
Authors: D Dooley
Journal: BMJ (1994)

Abortion is a moral issue affecting the identity and integrity of physicians and nurses. Ethical reasoning helps reasonable and sincere people who do not agree on abortion to understand the sources of disagreement and to explore shared principles in the differences. Discussions of abortion cannot be limited to the conflict between the rights of a woman to control her reproduction and the rights of a fetus to live. Religious, cultural, feminist, and political beliefs must also be considered. This complexity must be considered when examining whether physicians and nurses have rights to refuse to assist in abortion on conscientious grounds. People with fundamentally different moral outlooks already determine what is morally right or wrong, good or evil. Health professionals who refuse to assist in abortion base their decision on beliefs about moral duties, injunctions of natural law, and the essentially nonnegotiable rights of people to be protected from intentional harm. They know and regret the adverse effects for pregnant women but there is no compelling motivation to change their opposition to abortion. There is no morally neutral position from which to judge conscientious refusals in abortion. Society should develop a position that respects autonomy of belief and grants the right to physicians and nurses to conscientiously refuse to assist in abortions. In those countries where the abortion law grants physicians the right to refuse but not nurses, society needs to reflect on why nurses have been accorded second class professional and moral status. In those countries which have not yet formulated an abortion law, the government should consider how it can find enough health workers who will in good conscience assist in abortions. Governments must first seriously consider a presumptive right to conscientious refusal in abortion before health systems can redistribute sectors of responsibility among health workers and implement changes in recruitment policies for relevant specializations.
Cell Mechanics: Integrating Cell Responses to Mechanical Stimuli
Authors: Paul A. Janmey, Christopher A. McCulloch
Journal: Annual Review of Biomedical Engineering (2007)

Forces are increasingly recognized as major regulators of cell structure and function, and the mechanical properties of cells are essential to the mechanisms by which cells sense forces, transmit them to the cell interior or to other cells, and transduce them into chemical signals that impact a spectrum of cellular responses. Comparison of the mechanical properties of intact cells with those of the purified cytoskeletal biopolymers that are thought to dominate their elasticity reveal the extent to which the studies of purified systems can account for the mechanical properties of the much more heterogeneous and complex cell. This review summarizes selected aspects of current work on cell mechanics with an emphasis on the structures that are activated in cell-cell contacts, that regulate ion flow across the plasma membrane, and that may sense fluid flow that produces low levels of shear stress.
Survival Outcomes and Prognostic Factors in Mycosis Fungoides/Sézary Syndrome: Validation of the Revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer Staging Proposal
Authors: Nita Sally Agar, Emma Wedgeworth, Siobhan Crichton, Tracey J. Mitchell, Michael Cox, Silvia Ferreira, Alistair Robson, Eduardo Calonje, Catherine M. Stefanato, Elizabeth Mary Wain, Bridget Wilkins, Paul A. Fields, Alan Dean, Katherine Webb, Julia Scarisbrick, Stephen Morris, Sean J. Whittaker
Journal: Journal of Clinical Oncology (2010)

We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal.Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models.The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease. Disease progression occurred in 34%, and 26% of patients died due to MF/SS. A significant difference in survival and progression was noted for patients with early-stage disease having patches alone (T1a/T2a) compared with those having patches and plaques (T1b/T2b). Univariate analysis established that (1) advanced skin and overall clinical stage, increased age, male sex, increased lactate dehydrogenase (LDH), and large-cell transformation were associated with reduced survival and increased RDP; (2) hypopigmented MF, MF with lymphomatoid papulosis, and poikilodermatous MF were associated with improved survival and reduced RDP; and (3) folliculotropic MF was associated with an increased RDP. Multivariate analysis established that (1) advanced skin (T) stage, the presence in peripheral blood of the tumor clone without Sézary cells (B0b), increased LDH, and folliculotropic MF were independent predictors of poor survival and increased RDP; (2) large-cell transformation and tumor distribution were independent predictors of increased RDP only; and (3) N, M, and B stages; age; male sex; and poikilodermatous MF were only significant for survival.This study has validated the recently proposed ISCL/EORTC staging system and identified new prognostic factors.