tbuckley/cabot-search huggingface dataset:
Externally validated predictive clinical model for untreated del(17p13.1) chronic lymphocytic leukemia patients
Authors: Deborah M. Stephens, Amy S. Ruppert, William G. Weirda, Jeffrey A. Jones, Jennifer A. Woyach, Kami Maddocks, Samantha M. Jaglowski, Leslie A. Andritsos, Joseph M. Flynn, Michael R. Grever, Gerard Lozanski, Constantine Tam, Susan O'Brien, Michael J. Keating, Natarajan Muthusamy, Lynne V. Abruzzo, Nyla A. Heerema, John C. Byrd
Journal: American Journal of Hematology (2015)

Little is known about outcomes of patients with chronic lymphocytic leukemia (CLL) with del(17p13.1) karyotype at diagnosis. We reviewed 114 de novo del(17p13.1) CLL patients seen at our institution. Using proportional hazards models to identify pretreatment clinical variables significantly associated with treatment‐free survival (TFS) and overall survival (OS), we developed a simplified risk score for de novo del(17p13.1) CLL patients to predict TFS and OS based on these variables. These scores, particularly the very highest, can be utilized to identify high‐risk patients for expedient enrollment on clinical trials. Our data support careful observation for low‐risk patients, potentially preventing unnecessary use of aggressive therapies. Am. J. Hematol. 90:967–969, 2015. © 2015 Wiley Periodicals, Inc.
Augmentation of portal blood flow improves function of human cirrhotic liver
Authors: Jorge E. Cardoso, Chantal Gautreau, Prema Raj Jeyaraj, Dariusz Patrzalek, Brigitte Cherruau, Michel Vaubourdolle, Claire Legendre, Tadeusz Wroblewski, Didier Houssin
Journal: Hepatology (1994)

In cirrhotic livers, the intrahepatic resistance is increased and drug elimination and portal transhepatic flow are decreased. The aim of our work was to study the effect of a twofold increase in portal blood flow during 2 hr on the hemodynamic parameters, drug elimination and hepatic viability in eight isolated perfused human cirrhotic livers. Using an oxygenated recirculating system with independent arterial and portal flows, we perfused livers with Kreb’s buffer bicarbonate solution, bovine serum albumin (20 gm·L −1 ) and human red blood cells (hematocrit 20). The flow was maintained at a basal level of 0.713 ± 0.19 L/min for 1 hr and then increased and maintained for 2 hr at twice the basal flow. Portal pressure-portal flow curve slopes were linear (27.04 ± 21.06 mm Hg·L −1 ·min; range = 6.43 to 60.8) and correlated with intrahepatic resistance during the basal-flow period (r = 0.87, p &lt; 0.01). Parameters registered during the basal- and high-flow periods were compared by use of Student’s t test: portal pressure increased from 23.5 ± 7 to 37.3 ± 16.7 mm Hg (p &lt; 0.05); arterial pressure increased from 80.3 ± 19 to 103.5 ± 26 mm Hg (p &lt; 0.005); hepatic artery flow resistance increased 31.9 (from 690.1 ± 218 to 899.4 ± 269 mm Hg·L −1 ·min; p &lt; 0.005); indocyanine green clearance increased by 28.2 (from 86.0 ± 58.3 to 109.2 ± 74.8 ml·min −1 ·kg liver −1 ; p &lt; 0.04). No significant differences were observed in enzyme release, biliary flow (n = 5) and oxygen consumption. Histological examinations demonstrated sinusoidal dilatations in six of eight cases. These results suggest that better liver perfusion and function of cirrhotic nodules might be obtained by increasing portal flow and perfusion pressure. (Hepatology 1994;19:375-380).
A computational model of gene expression reveals early transcriptional events at the subtelomeric regions of the malaria parasite, Plasmodium falciparum
Authors: Matthias Scholz, Martin J Fraunholz
Journal: Genome biology (2008)

The malaria parasite, Plasmodium falciparum, replicates asexually in a well-defined infection cycle within human erythrocytes (red blood cells). The intra-erythrocytic developmental cycle (IDC) proceeds with a 48 hour periodicity. Based on available malaria microarray data, which monitored gene expression over one complete IDC in one-hour time intervals, we built a mathematical model of the IDC using a circular variant of non-linear principal component analysis. This model enables us to identify rates of expression change within the data and reveals early transcriptional events at the subtelomeres of the parasite's nuclear chromosomes. A delay between subtelomeric and central gene activities suggests that key events of the IDC are initiated at the subtelomeric regions of the P. falciparum nuclear chromosomes.
Oral Atovaquone Compared with Intravenous Pentamidine for Pneumocystis carinii Pneumonia in Patients with AIDS
Authors: M N Dohn, W G Weinberg, R A Torres, S E Follansbee, P T Caldwell, J D Scott, J C Gathe, D P Haghighat, J H Sampson, J Spotkov, S C Deresinski, R D Meyer, D J Lancaster
Journal: Annals of Internal Medicine (1994)

To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments.Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily.Multicenter study including university and community treatment facilities.Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized.Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued.As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to -17%; P < 0.001). Nine patients in each treatment group died during the study.Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events.
Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory ganglia during viral infection
Authors: Angus T. Stock, Jeffrey M. Smith, Francis R. Carbone
Journal: The Journal of Experimental Medicine (2014)

Infection induces the expression of inflammatory chemokines that recruit immune cells to the site of inflammation. Whereas tissues such as the intestine and skin express unique chemokines during homeostasis, whether different tissues express distinct chemokine profiles during inflammation remains unclear. With this in mind, we performed a comprehensive screen of the chemokines expressed by two tissues (skin and sensory ganglia) infected with a common viral pathogen (herpes simplex virus type 1). After infection, the skin and ganglia showed marked differences in their expression of the family of Cxcr2 chemokine ligands. Specifically, Cxcl1/2/3, which in turn controlled neutrophil recruitment, was up-regulated in the skin but absent from the ganglia. Within the ganglia, Cxcl2 expression and subsequent neutrophil recruitment was inhibited by type I interferon (IFN). Using a combination of bone marrow chimeras and intracellular chemokine staining, we show that type I IFN acted by directly suppressing Cxcl2 expression by monocytes, abrogating their ability to recruit neutrophils to the ganglia. Overall, our findings describe a novel role for IFN in the direct, and selective, inhibition of Cxcr2 chemokine ligands, which results in the inhibition of neutrophil recruitment to neuronal tissue.
Prostigmine Inhibition of Ventricular Fibrillation in the Hypothermic Dog
Authors: A. V. MONTGOMERY, ARTHUR E. PREVEDEL, HENRY SWAN
Journal: Circulation (1954)

This study shows that when prostigmine is given via coronary perfusion in the hypothermic dog, cardiac surgery can be performed without ventricular fibrillation resulting. This action of prostigmine seems to be due to an accumulation of acetylcholine, since prostigmine's antifibrillatory action can be reproduced by a continuous coronary perfusion of acetylcholine or by stimulation of the vagus nerve. A possible relationship between potassium and ventricular fibrillation is discussed.
Antidepressant Response in Patients With Major Depression Exposed to NSAIDs: A Pharmacovigilance Study
Authors: Patience J. Gallagher, Victor Castro, Maurizio Fava, Jeffrey B. Weilburg, Shawn N. Murphy, Vivian S. Gainer, Susanne E. Churchill, Isaac S. Kohane, Dan V. Iosifescu, Jordan W. Smoller, Roy H. Perlis
Journal: American Journal of Psychiatry (2012)

Coexisting general medical illness accounts for much of the previously reported association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and nonremission of treated depression. A modest but smaller relationship for NSAIDs remained when analyses included the comorbidity of patients in a large health care system and in the STAR*D study of antidepressant effectiveness. Resistance to antidepressant treatment is related to long-term NSAID use but not to intermittent use or to use of cyclo-oxygenase-2 (COX-2) inhibitors and salicylates.
Risk factors for oesophageal squamous dysplasia in adult inhabitants of a high risk region of China
Authors: W-Q Wei
Journal: Gut (2005)

<b>Background:</b> Oesophageal squamous cell carcinoma (OSCC) is a common cancer worldwide and has a very high mortality rate. Squamous dysplasia is the precursor lesion for OSCC and it can be seen during routine endoscopy with Lugol's iodine staining. We aimed to examine the risk factors for squamous dysplasia and determine if a risk model could be constructed which would be useful in selecting apparently healthy subjects for endoscopic screening in a high risk population in Linzhou, People's Republic of China. <b>Subjects and methods:</b> In this cross sectional study, 724 adult volunteers aged 40–65 years were enrolled. All subjects completed a questionnaire regarding potential environmental exposures, received physical and dental examinations, and underwent upper endoscopy with Lugol's iodine staining and biopsy. Subjects were categorised as having or not having histologically proven squamous dysplasia/early cancer. Risk factors for dysplasia were examined using univariate and multivariate logistic regression. The utility of the final multivariate model as a screening tool was assessed using a receiver operating characteristics curve. <b>Results:</b> We found that 230 of 720 subjects (32%) with complete data had prevalent squamous dysplasia. In the final multivariate model, more household members (odds ratio (OR) 1.12/member (95% confidence interval (CI) 0.99, 1.25)), a family history of cancer (OR 1.57 (95% CI 1.13-2.18)), higher systolic blood pressure OR 1.11/10 mm Hg (95% CI 1.03-1.19)), heating the home without a chimney (OR 2.22 (95% CI 1.27–3.86)), and having lost more but not all of your teeth (OR 1.91 for 12–31 teeth lost (95% CI 1.17–3.15)) were associated with higher odds of having dysplasia. Higher household income (OR 0.96/100 RMB (95% CI 0.91–1.00)) was associated with a lower odds of having dysplasia. Although we found several statistically significant associations, the final model had little ability to accurately predict dysplasia status, with maximum simultaneous sensitivity and specificity values of 57% and 54%, respectively. <b>Conclusions:</b> We found that risk factors for dysplasia were similar to those previously identified as risk factors for OSCC in this population. The final model did a poor job of identifying subjects who had squamous dysplasia. Other methods will need to be developed to triage individuals to endoscopy in this high risk population.
Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment
Authors: P. Hadji, M.S. Aapro, J.J. Body, N.J. Bundred, A. Brufsky, R.E. Coleman, M. Gnant, T. Guise, A. Lipton
Journal: Annals of Oncology (2011)
An RNA Interference Screen Identifies Metabolic Regulators <i>NR1D1</i> and <i>PBP</i> as Novel Survival Factors for Breast Cancer Cells with the <i>ERBB2</i> Signature
Authors: Antonis Kourtidis, Ritu Jain, Richard D. Carkner, Cheryl Eifert, M. Julia Brosnan, Douglas S. Conklin
Journal: Cancer Research (2010)

Abstract Overexpression of the adverse prognostic marker ERBB2 occurs in 30% of breast cancers; however, therapies targeting this gene have not proved to be as effective as was initially hoped. Transcriptional profiling meta-analyses have shown that there are ∼150 genes co-overexpressed with ERBB2, suggesting that these genes may represent alternative factors influencing ERBB2-positive tumors. Here we describe an RNA interference–based analysis of these genes that identifies transcriptional regulators of fat synthesis and storage as being critical for the survival of these cells. These transcription factors, nuclear receptor subfamily 1, group D, member 1 (NR1D1) and peroxisome proliferator activated receptor γ binding protein (PBP), both reside on ERBB2-containing 17q12-21 amplicons and are part of the ERBB2 expression signature. We show that NR1D1 and PBP act through a common pathway in upregulating several genes in the de novo fatty acid synthesis network, which is highly active in ERBB2-positive breast cancer cells. Malate dehydrogenase 1 and malic enzyme 1, enzymes that link glycolysis and fatty acid synthesis, are also regulated by NR1D1. The resulting high-level fat production from increased expression of these genes likely contributes to an abnormal cellular energy metabolism based on aerobic glycolysis. Together, these results show that the cells of this aggressive form of breast cancer are genetically preprogrammed to depend on NR1D1 and PBP for the energy production necessary for survival. Cancer Res; 70(5); 1783–92
Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating
Authors: Per H. Nilsson, Kristina N. Ekdahl, Peetra U. Magnusson, Hongchang Qu, Hiroo Iwata, Daniel Ricklin, Jaan Hong, John D. Lambris, Bo Nilsson, Yuji Teramura
Journal: Biomaterials (2012)
Immunization with a Lymphocytic Choriomeningitis Virus Peptide Mixed with Heat Shock Protein 70 Results in Protective Antiviral Immunity and Specific Cytotoxic T Lymphocytes
Authors: Anne-Marie T. Ciupitu, Max Petersson, Carey L. O'Donnell, Kevin Williams, Satish Jindal, Rolf Kiessling, Raymond M. Welsh
Journal: The Journal of Experimental Medicine (1998)

Heat shock proteins (hsp's) isolated from murine cancer cells can elicit protective immunity and specific cytotoxic T lymphocytes (CTLs) by channeling tumor-derived peptides bound to hsp's to the major histocompatibility class I antigen presentation pathway. Here we have investigated if hsp70 can be used in a novel peptide vaccine for the induction of protective antiviral immunity and memory CTLs. A CTL epitope from the well-defined lymphocytic choriomeningitis virus (LCMV) system was mixed with recombinant hsp70 in vitro under conditions that optimize peptide binding to hsp70. Mice were immunized with the hsp70–peptide mixture and challenged with LCMV. Virus titers were reduced 10–100-fold in these mice compared to control mice. Immunization with the hsp70–peptide mixture resulted in the development of CTL memory cells that could be reactivated during LCMV infection, and that in a 51Cr-release assay could lyse cells pulsed with the same peptide, but not cells pulsed with another LCMV peptide. These results show that hsp70 can be used with CTL epitopes to induce efficient protective antiviral immunity and the generation of peptide-specific CTLs. The results also demonstrate the usefulness of hsp70 as an alternative to adjuvants and DNA vectors for the delivery of CTL epitopes to antigen-presenting cells.
Characterization and Predictors of Asthma Exacerbations in Patients on Steps 4, 5 And 6 Therapy in the TENOR Cohort
Authors: W. Calhoun, T. Haselkorn, D.R. Mink, D.P. Miller, A. Dorenbaum, R. Zeiger
Journal: Journal of Allergy and Clinical Immunology (2012)
Beta 3-adrenoceptor agonists, BRL 37344 and SR 58611A, do not induce relaxation of human, sheep and guinea-pig airway smooth muscle in vitro
Authors: CA Martin, E Naline, H Bakdach, C Advenier
Journal: European Respiratory Journal (1994)

The existence of atypical- or beta 3-adrenoceptors has now been generally accepted. These receptors have been shown to be abundant in adipose tissue and in a number of gastrointestinal smooth muscle preparations. A recent study reported that beta 3-adrenoceptor stimulation mediated relaxation of isolated canine bronchial smooth muscle. The aim of the present study was to extend this observation to other species. We investigated the in vitro responses of guinea-pig, human and sheep bronchial smooth muscle to isoprenaline, salbutamol (a selective beta 2-adrenoceptor agonist), and BRL 37344 and SR 58611A (two presumably selective beta 3-adrenoceptor agonists). The preparations were precontracted to 60-70% of maximal tension with histamine 10(-6) M for guinea-pig and human bronchi, or acetylcholine 10(-6) M for sheep bronchi. In each species, SR 58611A produced a slight fall in tension of about 10% of the effects of theophylline (3 mM), but this decrease in tension was not significantly different from the spontaneous and weak relaxation observed with saline addition during the same duration of the experiment. These relaxations were not modified by either the nonselective beta-adrenoceptor antagonist propranolol or the selective beta 2-adrenoceptor antagonist ICI 118,551. In contrast, BRL 37344 induced a significant concentration-dependent fall in tension induced by both spasmogens. Its relaxant effects were inhibited both by propranolol and ICI 118,551 in human and guinea-pig airways, whereas on the isolated sheep bronchus BRL 37344-induced relaxations were only slightly, albeit significantly, reduced with either of the beta-adrenoceptor antagonists tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Targeted Glomerular Angiopoietin-1 Therapy for Early Diabetic Kidney Disease
Authors: Cecile Dessapt-Baradez, Adrian S. Woolf, Kathryn E. White, Jiaqi Pan, Jennifer L. Huang, Anthea A. Hayward, Karen L. Price, Maria Kolatsi-Joannou, Maelle Locatelli, Marine Diennet, Zoe Webster, Sarah J. Smillie, Viji Nair, Matthias Kretzler, Clemens D. Cohen, David A. Long, Luigi Gnudi
Journal: Journal of the American Society of Nephrology (2013)

Vascular growth factors play an important role in maintaining the structure and integrity of the glomerular filtration barrier. In healthy adult glomeruli, the proendothelial survival factors vascular endothelial growth factor-A (VEGF-A) and angiopoietin-1 are constitutively expressed in glomerular podocyte epithelia. We demonstrate that this milieu of vascular growth factors is altered in streptozotocin-induced type 1 diabetic mice, with decreased angiopoietin-1 levels, VEGF-A upregulation, decreased soluble VEGF receptor-1 (VEGFR1), and increased VEGFR2 phosphorylation. This was accompanied by marked albuminuria, nephromegaly, hyperfiltration, glomerular ultrastructural alterations, and aberrant angiogenesis. We subsequently hypothesized that restoration of angiopoietin-1 expression within glomeruli might ameliorate manifestations of early diabetic glomerulopathy. Podocyte-specific inducible repletion of angiopoietin-1 in diabetic mice caused a 70% reduction of albuminuria and prevented diabetes-induced glomerular endothelial cell proliferation; hyperfiltration and renal morphology were unchanged. Furthermore, angiopoietin-1 repletion in diabetic mice increased Tie-2 phosphorylation, elevated soluble VEGFR1, and was paralleled by a decrease in VEGFR2 phosphorylation and increased endothelial nitric oxide synthase Ser(1177) phosphorylation. Diabetes-induced nephrin phosphorylation was also reduced in mice with angiopoietin-1 repletion. In conclusion, targeted angiopoietin-1 therapy shows promise as a renoprotective tool in the early stages of diabetic kidney disease.
Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy
Authors: Lawrence A. Yannuzzi, K.Bailey Freund, Mauro Goldbaum, Baldo Scassellati-Sforzolini, David R. Guyer, Richard F. Spaide, David Maberley, Doric W.K. Wong, Jason S. Slakter, John A. Sorenson, Yale L. Fisher, Dennis A. Orlock
Journal: Ophthalmology (2000)
The effect of azathioprine on gammaglobulin synthesis in man
Authors: Joshua Levy, Eugene V. Barnett, Norman S. MacDonald, James R. Klinenberg, Carl M. Pearson
Journal: Journal of Clinical Investigation (1972)

The effect of azathioprine therapy on gammaglobulin synthesis was evaluated in nine patients with rheumatic disorders. The rates of synthesis of IgG and IgM were calculated before and after 4 months of azathioprine treatment using turnover studies of radioiodinated gammaglobulins. The synthesis of IgG decreased 33.4% of the initial IgG synthetic rate. Seven of nine patients showed reductions of IgG synthesis ranging from 16.8 to 74.1%. IgM production decreased from 24.5 to 74.2% in eight of nine patients with a mean reduction of 40.9%. Studies before and after a control period of 4 months of placebo in six patients revealed a mean increase in IgG and IgM synthesis. Serum immunoglobulin concentrations after 4 months of azathioprine treatment were not consistently reduced and did not parallel changes in immunoglobulin synthesis. Reduced gammaglobulin synthesis may play a role in the therapeutic action of this and other "immunosuppressive" drugs.
Lipid laden macrophages in bronchoalveolar lavage as a marker of pulmonary aspiration secondary to acid and non-acid gastroesophageal reflux
Authors: Jayakumar Mahalingam Arumugam, Caroline Hartt, Babu Vadamalayan, Theodore Patel, Hizbullah Shaikh, Gary Ruiz, Atul Gupta
Journal: European Respiratory Journal (2014)

Background:Gastroesophageal reflux (GOR) is known to cause and exacerbate respiratory problems. Presence of lipid-laden macrophages (LLM) in the airways is postulated as a marker of aspiration. However, little is known about the relationship of bronchoalveolar lavage (BAL) LLM and acid/non-acid GOR. Aim:To assess the relationship between acid/non-acid GOR measured by pH/impedance study and BAL LLM in children with respiratory problems. Method:Prospective data from 53 children who underwent flexible bronchoscopy, BAL and pH/impedance study on the same day between January 2010 and October 2013 were analysed. LLM scoring was done using Colombo index. A scatter plot and linear regression analysis were used to assess the correlation between reflux detected by pH study and percentage of LLM. Results:The cohort consisted of patients with chronic cough(n= 22),cystic fibrosis(n= 16) and difficult asthma(n= 15). 41 of these children had oesophageal pH study and 12 had impedance study. There was significant but weak positive correlation between LLM index in BAL and duration of acid reflux measured by pH study (Pearson9s correlation coefficient=0.14; Spearman9s rank = 0.35). BAL LLM as a marker of aspiration as indicated by pH study has a sensitivity of 87.5% (95% CI: 61.62% to 98.08%) and a specificity of 28% (95% CI: 12.12% to 49.39%). The same as indicated by impedance study has a sensitivity of 75% (95% CI: 20.34% to 95.88%) and a specificity of 50% (95% CI: 16.01% to 83.99%). Conclusion:In detecting acidic and non-acidic GOR related pulmonary aspiration in children with respiratory problems, LLM scoring in BAL has poor specificity and sensitivity.