tbuckley/cabot-search huggingface dataset:
Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl
Authors: Ellen Weisberg, Paul W. Manley, Werner Breitenstein, Josef Brüggen, Sandra W. Cowan-Jacob, Arghya Ray, Brian Huntly, Doriano Fabbro, Gabriele Fendrich, Elizabeth Hall-Meyers, Andrew L. Kung, Jürgen Mestan, George Q. Daley, Linda Callahan, Laurie Catley, Cara Cavazza, Azam Mohammed, Donna Neuberg, Renee D. Wright, D. Gary Gilliland, James D. Griffin
Journal: Cancer Cell (2005)
Increased erythrocyte aggregation as an indicator for an aggressive clinical course in Behcet's disease: a prospective study
Authors: H. Demiroglu, S. Yalcin, Y. Buyukasik, O. I. Ozcebe, S. Dundar
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> Changes in blood rheology, especially increased erythrocyte aggregation (EA) might play an important part in the development of arterial and venous thrombotic lesions. A prospective study was designed to evaluate EA in patients with Behçet's disease (BD) and to see if this parameter is predictive for the future development of vascular complications, such as deep vein thrombosis of various organ systems and uveitis. <h3>METHODS</h3> EA was measured by a photometric Myrenne aggregometer in 38 patients with BD at the time of initial diagnosis and in 40 age and sex matched healthy controls (HC). <h3>RESULTS</h3> During a median follow up period of 13.5 months, 13 patients developed vascular-ocular complications (eight deep vein thrombosis, nine uveitis, and four both deep vein thrombosis and uveitis). Patients were further divided into two groups: BD-a with mucocutaneous symptoms and arthritis only; BD-b with associated vascular-ocular complications. EA values at high shear rate (M) and at low shear rate (M1) were compared among the groups. <h3>CONCLUSION</h3> EA values at M and M1 were significantly higher in BD-b than BD-a and HC (p&lt;0.001). These results suggest that determination of EA rates might be useful to identify subgroups who are likely candidates for developing vascular-ocular complications in BD and management of factors known to affect blood rheology might be beneficial.
Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis
Authors: Yoann Rombouts, Ewoud Ewing, Lotte A van de Stadt, Maurice H J Selman, Leendert A Trouw, André M Deelder, Tom W J Huizinga, Manfred Wuhrer, Dirkjan van Schaardenburg, René E M Toes, Hans U Scherer
Journal: Annals of the Rheumatic Diseases (2013)

Objective To determine whether anticitrullinated protein antibodies (ACPA) exhibit specific changes in Fc glycosylation prior to the onset of arthritis. Methods Serum samples of patients with ACPA-positive arthralgia (n=183) were collected at baseline and at various time points of follow-up. 105 patients developed arthritis after a median of 12 months (IQR 6–24) and were classified as having either rheumatoid arthritis (RA, n=48) or undifferentiated arthritis (UA, n=57) based on the 1987 American College of Rheumatology (ACR) criteria. ACPA and total serum IgG were isolated by affinity purification and cleaved by trypsin. ACPA-IgG1 Fc-glycopeptides were subsequently analysed by nano-liquid chromatography mass spectrometry and compared to those of total IgG1. Results At baseline, ACPA-IgG1 and total IgG1 from arthralgia patients displayed similar Fc glycosylation patterns. By contrast, at the onset of arthritis, ACPA exhibited a decrease in galactose residues in RA patients, but not in UA patients. This decrease occurred around 3 months prior to diagnosis and was paralleled by an increase in systemic inflammation (erythrocyte sedimentation rate). Galactosylation of total IgG1 was also decreased in RA, but this did not precede the onset of arthritis. Interestingly, we additionally noted a higher degree of ACPA-IgG1 Fc core fucosylation at baseline as compared with total IgG1, which further increased prior to diagnosis. Conclusions ACPA display significant changes in Fc galactosylation and fucosylation prior to the onset of RA. These changes towards a more pro-inflammatory phenotype could be involved in driving the disease process.
One-Year Survival Following Early Revascularization for Cardiogenic Shock
Authors: Judith S. Hochman
Journal: JAMA (2001)

ARDIOGENIC SHOCK (CS) IS the leading cause of death for patients hospitalized with acute myocardial infarction (AMI), 1,2 and mortality remains high during the following year. 3,4The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) Trial demonstrated a nonsignificant reduction in 30day mortality (56% vs 47%) when early revascularization (ERV) was compared with a strategy of initial medical stabilization (IMS), with a larger difference between the groups at 6 months. 5In this article, we report the 1-year survival, a prespecified secondary end point of the SHOCK Trial.
Randomized, Placebo-Controlled Trial of Mixed Amphetamine Salts for Symptoms of Comorbid ADHD in Pediatric Bipolar Disorder After Mood Stabilization With Divalproex Sodium
Authors: Russell E. Scheffer, Robert A. Kowatch, Thomas Carmody, A. John Rush
Journal: American Journal of Psychiatry (2004)

The purpose of this study was to determine whether adjunctive use of a psychostimulant (mixed amphetamine salts) was safe and efficacious for treatment of symptoms of attention deficit hyperactivity disorder (ADHD) in pediatric outpatients with bipolar I or bipolar II disorder and concurrent ADHD whose manic symptoms had been stabilized through treatment with divalproex sodium.An 8-week open-label trial of divalproex sodium to control manic symptoms and to discern the effect of divalproex sodium on ADHD was followed by a 4-week randomized, double-blind, placebo-controlled crossover trial to determine if mixed amphetamine salts was safe and effective for treatment of ADHD symptoms. Patients in the crossover trial continued to receive divalproex sodium. Diagnoses, made by clinical interview, were confirmed with the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia. The Young Mania Rating Scale (for manic symptoms) and the Clinical Global Impression of improvement (for ADHD symptoms) were the primary outcome measures.Forty subjects ages 6-17 years with bipolar I disorder (77.5%) or bipolar II disorder (22.5%) and a Young Mania Rating Scale score > or =14 entered open treatment with divalproex sodium. With divalproex sodium, 32 subjects achieved > or =50% reduction in Young Mania Rating Scale baseline scores, but only three participants had significant improvement in ADHD symptoms. For the 30 subjects who entered the placebo-controlled crossover trial, mixed amphetamine salts was significantly more effective than placebo for ADHD symptoms. No significant side effects or worsening of manic symptoms was observed.Pediatric patients with bipolar disorder and concurrent ADHD can be safely and effectively treated with mixed amphetamine salts after their manic symptoms are stabilized with divalproex sodium. Divalproex sodium alone (8-week trial) is not an effective treatment for ADHD in the context of bipolar disorder.
Systemic CTLA-4 Blockade Ameliorates Glioma-Induced Changes to the CD4+ T Cell Compartment without Affecting Regulatory T-Cell Function
Authors: Peter E. Fecci, Hidenobu Ochiai, Duane A. Mitchell, Peter M. Grossi, Alison E. Sweeney, Gary E. Archer, Thomas Cummings, James P. Allison, Darell D. Bigner, John H. Sampson
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4+ T cell numbers and function. We have previously shown that increased regulatory T cell (Treg) fractions in these patients explain T-cell functional deficits. Our murine glioma model recapitulates these findings. Here, we investigate the effects of systemic CTLA-4 blockade in this model. Experimental Design: A monoclonal antibody (9H10) to CTLA-4 was employed against well-established glioma. Survival and risks for experimental allergic encephalomyelitis were assessed, as were CD4+ T cell numbers and function in the peripheral blood, spleen, and cervical lymph nodes. The specific capacities for anti-CTLA-4 to modify the functions of regulatory versus CD4+CD25− responder T cells were evaluated. Results: CTLA-4 blockade confers long-term survival in 80% of treated mice, without eliciting experimental allergic encephalomyelitis. Changes to the CD4 compartment were reversed, as anti-CTLA-4 reestablishes normal CD4 counts and abrogates increases in CD4+CD25+Foxp3+GITR+ regulatory T cell fraction observed in tumor-bearing mice. CD4+ T-cell proliferative capacity is restored and the cervical lymph node antitumor response is enhanced. Treatment benefits are bestowed exclusively on the CD4+CD25− T cell population and not Tregs, as CD4+CD25− T cells from treated mice show improved proliferative responses and resistance to Treg-mediated suppression, whereas Tregs from the same mice remain anergic and exhibit no restriction of their suppressive capacity. Conclusions: CTLA-4 blockade is a rational means of reversing glioma-induced changes to the CD4 compartment and enhancing antitumor immunity. These benefits were attained through the conferment of resistance to Treg-mediated suppression, and not through direct effects on Tregs.
Real-time Magnetic Resonance–guided High-intensity Focused Ultrasound Focal Therapy for Localised Prostate Cancer: Preliminary Experience
Authors: Alessandro Napoli, Michele Anzidei, Cosimo De Nunzio, Gaia Cartocci, Valeria Panebianco, Carlo De Dominicis, Carlo Catalano, Federico Petrucci, Costantino Leonardo
Journal: European Urology (2012)
Mechanism of global functional recovery despite sustained postischemic regional stunning.
Authors: W E Lawrence, W L Maughan, D A Kass
Journal: Circulation (1992)

BACKGROUND The mechanisms whereby reperfusion of a 20-minute coronary occlusion result in global functional recovery despite persistent regional dysfunction were studied in 11 open-chest reflex-blocked dogs. METHODS AND RESULTS Pressure-volume and pressure-thickness relations were simultaneously determined before, during, and after reperfusion of left anterior descending artery (LAD) occlusion. Wall thickness was determined by sonomicrometry in both ischemic and remote regions. Chamber systolic function was assessed by end-systolic pressure-volume relations (ESPVR) obtained by conductance catheter and defined by a slope (Ees) and volume shift at a common end-systolic pressure (delta Ves). LAD occlusion produced regional systolic thinning (-7 +/- 6%) and global left ventricular dysfunction (ESPVR shifted rightward (delta Ves = +8.6 +/- 5.1 ml, p less than 0.001) with no Ees change). After nearly 1 hour of reperfusion, LAD region thickening remained markedly reduced at 4 +/- 7% (versus 23 +/- 8%, control), yet chamber systolic function fully recovered (ESPVR shifted back leftward delta Ves = -8.9 +/- 6.5 ml). Ischemia induced a leftward shift and systolic thinning of LAD region pressure-thickness relations. Reperfusion returned end-systolic pressure-thickness relations halfway to their control position and diastolic relations fully to control position. This was primarily due to increased passive stiffening in about half the hearts and a partial return of active function in the remaining ones. The net effect was to eliminate systolic thinning over a physiological loading range, thus normalizing chamber systolic performance. Reflex activation, remote hyperfunction, or altered chamber loading did not account for the postreperfusion disparity between global and regional function. CONCLUSIONS These data suggest a mechanism to account for greater functional benefits of reperfusion beyond that anticipated from regional wall motion analysis.
Class I transplantation antigens in solution in body fluids and in the urine. Individuality signals to the environment.
Authors: P B Singh, R E Brown, B Roser
Journal: The Journal of Experimental Medicine (1988)

Classical class I transplantation antigens present in solution in the body fluids have been studied. These antigens have been found in a monomeric, soluble form in blood, lymph, and urine, and a major source is the hemopoietic system which gives rise to cells that secrete these molecules into the blood. The cell types most probably involved in their secretion are of the macrophage/dendritic cell lineage. The serum molecule is a heterodimer with a heavy chain of 39,000 mol wt associated noncovalently with beta 2-microglobulin and is present in serum at a concentration between 350 and 390 ng/ml. These molecules have a short half-life of 2.7 h and are excreted into the environment via the kidneys in the urine. In the urine, greater than 90% of the molecules are degraded into smaller fragments. This finding that normal metabolic processes lead to the excretion of classical highly polymorphic class I molecules in the urine provides a direct explanation in molecular terms of the ability of animals to identify individuals on the basis of urinary odor. Since intact class I molecules are unlikely to be the odoriferous component in the urine, two hypotheses have been suggested. Either small fragments of class I molecules are detected or the molecule acts as a carrier that transports volatiles from the serum into the urine where they are released, giving rise to the class I-associated odor.
Relapse rate, renal survival, and cancer morbidity in patients with Wegener's granulomatosis or microscopic polyangiitis with renal involvement.
Authors: K W Westman, P G Bygren, H Olsson, J Ranstam, J Wieslander
Journal: Journal of the American Society of Nephrology (1998)

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are both frequently associated with antineutrophil cytoplasmic autoantibodies (ANCA). Immunosuppressive treatment has dramatically improved outcome for these patients, but today we have to deal with the problems of relapses, cases refractory to treatment, and long-term side effects of therapy. This study comprises a consecutive series of 123 patients with WG (n=56) or MPA (n=67) with biopsy-confirmed renal involvement, followed up for a median of 55 mo (range, 0.1 to 273.2 mo). ANCA was detected by enzyme-linked immunosorbent assay in 97% of patients. Nearly half of the patients (46%) relapsed. There was no statistically significant difference in overall relapse rate according to type of ANCA. Renal survival was 78% in patients alive at the end of follow-up. Three variables seemed important for renal survival: serum creatinine, the titer of proteinase 3-ANCA measured by capture enzyme-linked immunosorbent assay, and B thrombocyte count, at time of referral. Cancer incidence data were obtained from the population-based South Swedish Regional Tumor Registry. Standardized morbidity ratio was calculated using expected values from the health care region. We found an 11-fold increase in risk for bladder cancer in patients treated with cyclophosphamide for at least 12 mo. Skin carcinoma had the strongest relationship with azathioprine use for at least 12 mo and with corticosteroid therapy for at least 48 mo. In addition, four patients developed myelodysplastic syndrome and five had carcinoma in situ of the skin. Because the therapeutic regimen used today is not efficient enough to prevent relapses and is associated with a host of side effects, of which the risk for cancer is by far the most important, improved therapy and medical care are needed for patients with WG and MPA.
Targeted and Nontargeted Effects of Ionizing Radiation That Impact Genomic Instability
Authors: Christopher A. Maxwell, Markus C. Fleisch, Sylvain V. Costes, Anna C. Erickson, Arnaud Boissière, Rishi Gupta, Shraddha A. Ravani, Bahram Parvin, Mary Helen Barcellos-Hoff
Journal: Cancer Research (2008)

Abstract Radiation-induced genomic instability, in which the progeny of irradiated cells display a high frequency of nonclonal genomic damage, occurs at a frequency inconsistent with mutation. We investigated the mechanism of this nontargeted effect in human mammary epithelial cells (HMEC) exposed to low doses of radiation. We identified a centrosome-associated expression signature in irradiated HMEC and show here that centrosome deregulation occurs in the first cell cycle after irradiation, is dose dependent, and that viable daughters of these cells are genomically unstable as evidenced by spontaneous DNA damage, tetraploidy, and aneuploidy. Clonal analysis of genomic instability showed a threshold of &amp;gt;10 cGy. Treatment with transforming growth factor β1 (TGFβ), which is implicated in regulation of genomic stability and is activated by radiation, reduced both the centrosome expression signature and centrosome aberrations in irradiated HMEC. Furthermore, TGFβ inhibition significantly increased centrosome aberration frequency, tetraploidy, and aneuploidy in nonirradiated HMEC. Rather than preventing radiation-induced or spontaneous centrosome aberrations, TGFβ selectively deleted unstable cells via p53-dependent apoptosis. Together, these studies show that radiation deregulates centrosome stability, which underlies genomic instability in normal human epithelial cells, and that this can be opposed by radiation-induced TGFβ signaling. [Cancer Res 2008;68(20):8304–11]
Tumor Antigens and Tumor-Host Relationships
Authors: R W Baldwin, M R Price
Journal: Annual Review of Medicine (1976)

The view that immunological reactions play a role in modifying or even controlling malignant disease has now gained wide acceptance. This has developed from well­ substantiated investigations showing that many, although by no means all, experi­ mental animal tumors induced by chemical carcinogens or oncogenic viruses, as well as those of unknown (spontaneous) etiology, elicit immune rejection responses against the tumor (I, 2). Consequently, hosts preimmunized against these tumors (e.g. by implantation of radiation-attenuated cells) will reject a subsequent challenge with the same tumor. Comparable evidence for host defenses in human malignant disease is not avail­ able, apart from limited stu4ies indicating that autografted tumor cells do not readily take (3). There are, however, a small number of impressive examples from clinical investigations suggesting, but not ·proving, that in certain circumstances immunological reactions may control malignant disease. These include reports of spontaneous remissions in melanoma, neuroblastoma, and renal cell carcinoma (4), as well as remissions occurring in Burkitt's lymphoma patients receiving minimal chemotherapy (5). Conversely, there is substantial evidence of increased incidences of malignant tumors in patients receiving continuous immunosuppressive therapy follC'wing organ transplantation (6). Finally there is an increasing number of studies showing that procedures designed to heighten patients' general immunocompetence or to specifically boost tumor-immune responses may have therapeutic potential. Broadly speaking, however, the major body of evidence supporting the concept that human tumors express neoantigens similar to those detected in experimental animal tumors has been derived from in vitro assays of cell-mediated and humoral antibody responses to tumor cells (7). In addition there are a number of reports showing that cancer patients exhibit delayed hypersensitivity responses to tumor extracts (8).
Synaptic Mechanisms Underlying Rapid Antidepressant Action of Ketamine
Authors: Ege T. Kavalali, Lisa M. Monteggia
Journal: American Journal of Psychiatry (2012)

Recent clinical studies have demonstrated that a single subpsychotomimetic dose of ketamine, an ionotropic glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, produces a rapid antidepressant response in patients with major depressive disorder, with effects lasting up to 2 weeks. Despite enthusiasm about this unexpected efficacy of ketamine, its widespread use as a fast-acting antidepressant in routine clinical settings is curtailed by its abuse potential as well as possible psychotomimetic effects. However, the ability of ketamine to produce a rapid and long-lasting antidepressant response in patients with depression provides a unique opportunity for investigation of mechanisms that mediate these clinically relevant behavioral effects. From a mechanistic perspective, it is easy to imagine how activation of NMDA receptors may trigger cellular and behavioral responses; it is relatively more difficult, however, to envision how transient blockade of one of the key pathways for neuronal communication produces a persistent beneficial effect. The authors discuss recent work linking ketamine's mechanism of action to homeostatic synaptic plasticity processes activated after suppression of NMDA-mediated glutamatergic neurotransmission. They focus on their recent work demonstrating that ketamine-mediated blockade of NMDA receptors at rest deactivates eukaryotic elongation factor 2 (eEF2) kinase, resulting in reduced eEF2 phosphorylation and desuppression of rapid dendritic protein translation, including BDNF (brain-derived neurotrophic factor), which then contributes to synaptic plasticity mechanisms that mediate long-term effects of the drug. The authors also explore possible molecular strategies to target spontaneous neurotransmitter release selectively to help uncover novel presynaptic avenues for the development of fast-acting antidepressants and possibly psychoactive compounds with effectiveness against other neuropsychiatric disorders.
Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy
Authors: S. Lorenzen, P. Thuss-Patience, S.E. Al-Batran, F. Lordick, B. Haller, T. Schuster, C. Pauligk, K. Luley, D. Bichev, G. Schumacher, N. Homann
Journal: Annals of Oncology (2013)
Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese
Authors: Ping-Ping Cao, Hua-Bin Li, Bao-Feng Wang, Shui-Bin Wang, Xue-Jun You, Yong-Hua Cui, De-Yun Wang, Martin Desrosiers, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2009)
Alpha heavy chain disease lacking secretory alpha chain, with cobblestone appearance of the small intestine and duodenal ulcer demonstrated by endoscopy.
Authors: T Hibi, H Asakura, K Kobayashi, Y Munakata, S Kano, M Tsuchiya, T Teramoto, Y Uematsu
Journal: Gut (1982)

Ultrastructural and immunohistochemical studies of the small intestine are described in a Japanese patient with alpha heavy chain disease who had a history of colonic ulcers. Endoscopic examinations revealed multiple gastric erosion, duodenal ulcer, and a thickened, cobblestone-like pattern composed of small nodules in the duodenum and jejunum, which was similar in appearance to Crohn9s disease. An electron microscopic study showed that the numerous, infiltrated cells in the jejunal lamina propria were matured plasma cells with atypical structure of the organelles. These plasma cells had alpha heavy chain protein devoid of light chain. Although secretory component was demonstrated normally in the epithelial cells by immunofluorescent methods, no association of this component with alpha heavy chain protein could be observed in any of the plasma and epithelial cells of this case. These facts suggest the absence of secretory alpha chain or secretory IgA, and a deficiency of the mucosal secretory immune system in this patient.