tbuckley/cabot-search huggingface dataset:
Clinical and Cognitive Factors Associated With Verbal Memory Task Performance in Patients With Schizophrenia
Authors: Gildas Brébion, Jack M. Gorman, Dolores Malaspina, Zafar Sharif, Xavier Amador
Journal: American Journal of Psychiatry (2001)

The authors have previously shown the role of depression, slowing of processing speed, and selective attention deficit in verbal memory task performance in schizophrenia. They wished to determine the specific contribution of each of these factors to various types of memory impairment.The negative symptom score from the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale score, a measure of processing speed, and a measure of selective attention were entered as predictors in regression analyses. Furthermore, analyses of covariance were conducted on the memory measures to test the significance of the differences between schizophrenic patients and healthy comparison subjects after control for processing speed and selective attention.Depression was associated only with deep encoding reflected by semantic clustering. Selective attention was associated only with superficial encoding reflected by serial recall. Slowing of processing speed was associated with both deep and superficial encoding. Negative symptoms were not associated with memory impairment except for the avolition item from the Scale for the Assessment of Negative Symptoms. Processing speed accounted for all the group differences on the memory measures that reflected superficial encoding. In addition, a subgroup of patients with no or minor depression was not significantly impaired on deep encoding relative to the healthy comparison group.The authors suggest that verbal memory impairment in schizophrenia is a consequence of depression and slowness, rather than a primary feature of the disease.
Fractalkine (CX3CL1)– and Interleukin-2–Enriched Neuroblastoma Microenvironment Induces Eradication of Metastases Mediated by T Cells and Natural Killer Cells
Authors: Yan Zeng, Nicole Huebener, Stefan Fest, Silke Weixler, Ulrike Schroeder, Gerhard Gaedicke, Rong Xiang, Alexander Schramm, Angelika Eggert, Ralph A. Reisfeld, Holger N. Lode
Journal: Cancer Research (2007)

Abstract Fractalkine (FKN) is a unique CX3C chemokine (CX3CL1) known to induce both adhesion and migration of leukocytes mediated by a membrane-bound and a soluble form, respectively. Its function is mediated through CX3C receptor (CX3CR), which is expressed by TH1 immune cells including T cells and natural killer (NK) cells. FKN was shown to be expressed in &amp;gt;90% of 68 neuroblastoma samples as determined by cDNA microarray analysis. Here, we characterized the effect of FKN in the neuroblastoma microenvironment using a syngeneic model genetically engineered to secrete FKN. We show FKN-mediated migration, adhesion, and IFN-γ secretion of immune effector cells, but limited antineuroblastoma activity, in vitro and in vivo. Therefore, we tested the hypothesis that a combined increase of FKN and interleukin-2 (IL-2) in the neuroblastoma microenvironment induces an effective antitumor immune response. For this purpose, IL-2 was targeted to ganglioside GD2, which is highly expressed on neuroblastoma tissue, using an anti-GD2 antibody IL-2 immunocytokine (ch14.18-IL-2). Only mice bearing FKN- and IL-2–enriched neuroblastoma tumors exhibited a reduction in primary tumor growth and a complete eradication of experimental liver metastases. The depletion of T cells and NK cells in vivo abrogated the effect, and these effector cells showed the highest cytolytic activity in vitro. Finally, only the FKN- and IL-2–enriched neuroblastoma microenvironment resulted in T-cell activation and the release of proinflammatory cytokines. In summary, we showed for the first time the immunologic mechanisms by which targeted IL-2 treatment of neuroblastoma with an FKN-rich microenvironment induces an effective antitumor response. [Cancer Res 2007;67(5):2331–8]
Molecular Chaperones as a Common Set of Proteins That Regulate the Invasion Phenotype of Head and Neck Cancer
Authors: Ching-Chi Chiu, Chien-Yu Lin, Li-Yu Lee, Yin-Ju Chen, Ya-Ching Lu, Hung-Ming Wang, Chun-Ta Liao, Joseph Tung-Chieh Chang, Ann-Joy Cheng
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The goal of this study was to establish a common set of molecules that regulate cell invasion in head and neck cancer (HNC). Experimental Design: Five invasive sublines derived from HNC cell lines were established using the Matrigel selection method. Proteomic technology, MetaCore algorithm, and reverse transcriptase-PCR methods were used to search for molecules that contribute to the invasion phenotype. Cellular functional analyses and clinical association studies were applied to examine the significance of the molecules. Results: Fifty-two proteins were identified in more than two of the four independent proteomic experiments, including 10 (19%) molecular chaperones. Seven chaperones were confirmed to be differentially expressed in five sublines, Hsp90α, Hsp90β, Hsp90-B1/Gp96, Hsp70-A5/Grp78, and HYOU1, that upregulate, whereas Hsp60 and glucosidase-α neutral AB (GANAB) downregulate. Four molecules were further investigated. In all cell lines, knockdown of Hsp60 or GANAB and silencing of Gp96 or Grp78 considerably enhanced or reduced cell migration and invasion, respectively. Clinical association studies consistently revealed that low levels of Hsp60 or GANAB and high levels of Gp96 or Grp78 are significantly associated with advanced cancer (P &amp;lt; 0.001 to P = 0.047, respectively, for the four molecules) and poor survival (P &amp;lt; 0.001 to P = 0.025, respectively, for the four molecules). Conclusion: Our study defined molecular chaperones as a common set of proteins that regulate the invasion phenotype of HNC. Loss of the tumor suppression function of Hsp60 or GANAB and acquisition of the oncogenic function of Gp96 or Grp78 contribute to aggressive cancers. These molecules may serve as prognostic markers and targets for cancer drug development. Clin Cancer Res; 17(14); 4629–41. ©2011 AACR.
Differential STAT3, STAT5, and NF-κB activation in human hematopoietic progenitors by endogenous interleukin-15: implications in the expression of functional molecules
Authors: Julien Giron-Michel, Anne Caignard, Manuela Fogli, Danièle Brouty-Boyé, Diane Briard, Marc van Dijk, Raffaella Meazza, Silvano Ferrini, Caroline Lebousse-Kerdilès, Denis Clay, Heidi Bompais, Salem Chouaib, Bruno Péault, Bruno Azzarone
Journal: Blood (2003)
Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial
Authors: George L Bakris, Pantelis A Sarafidis, Matthew R Weir, Björn Dahlöf, Bertram Pitt, Kenneth Jamerson, Eric J Velazquez, Linda Staikos-Byrne, Roxzana Y Kelly, Victor Shi, Yann-Tong Chiang, Michael A Weber
Journal: The Lancet (2010)
Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL–positive leukemic cells
Authors: Ruriko Tanaka, Matthew S. Squires, Shinya Kimura, Asumi Yokota, Rina Nagao, Takahiro Yamauchi, Miki Takeuchi, Hisayuki Yao, Matthias Reule, Tomoko Smyth, John F. Lyons, Neil T. Thompson, Eishi Ashihara, Oliver G. Ottmann, Taira Maekawa
Journal: Blood (2010)
Plasma histamine concentration during propranolol induced bronchoconstriction.
Authors: P W Ind, P J Barnes, M J Brown, C T Dollery
Journal: Thorax (1985)

The mechanism of propranolol induced bronchoconstriction in asthma is uncertain, as airway beta adrenoceptors are not innervated by sympathetic nerves and circulating adrenaline concentrations are not raised. Propranolol 10 mg was infused over 27 minutes in 14 subjects with mild asthma. Peak expiratory flow (PEF) decreased by 80-235 l/min (17-51% of baseline) in nine subjects, who were called "responders," and by less than 50 l/min (12% of baseline) in five "non-responders". These two groups did not differ in baseline ventilatory function or in any clinical characteristic. In "responders" mean PEF had decreased significantly from 440 to 390 l/min after infusion of propranolol 2.1 mg, though the maximum fall in PEF occurred during or within five minutes of the end of the infusion. In nine of the subjects (six "responders" and three "non-responders") the possibility that propranolol induced bronchoconstriction is due to blockade of mast cell beta receptors leading to increased mediator release was examined by measurement of plasma histamine concentration as an index of mast cell degranulation. There was no consistent change in plasma histamine concentration in either group. No evidence of increased mast cell mediator release has been found in association with propranolol induced bronchoconstriction.
1054-149 Applicability of radial versus tangential strain rate measurements for separating normal and abnormal muscle segments of the left ventricle: In vitro study using an extracted pig heart
Authors: Giant C Lin, Yin Kan Hwee, Jessica E Coffman, Margaret S Soper, Brent J Barber, Xiaokui Li, David J Sahn
Journal: Journal of the American College of Cardiology (2004)
Elevation of systemic matrix metalloproteinases 2 and 7 and tissue inhibitor of metalloproteinase 2 in patients with a history of Achilles tendon rupture: pilot study
Authors: B. Pasternak, T. Schepull, P. Eliasson, P. Aspenberg
Journal: British Journal of Sports Medicine (2008)

Objectives In this study, serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between patients with a history of Achilles tendon rupture and blood donor controls were compared, and their relation to mechanical properties of the tendons during healing were studied. Methods More than 3 years after injury, serum levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9 and MMP-13, TIMP-1 and TIMP-2 in eight patients who had Achilles tendon rupture were measured. Twelve blood donors served as controls. During the early phase of healing, the tendon modulus of elasticity was calculated from radiostereometric data and tendon cross-sectional area. Results Patients with a history of Achilles tendon rupture had increased levels of MMP-2 (median difference 10%, p=0.01), MMP-7 (median difference 15%, p=0.02) and TIMP-2 (median difference 36%, p=0.02), compared with controls. Levels of MMP-7, measured 3 years after injury, correlated inversely to tendon modulus of elasticity (r s =20.83, p=0.02) and positively to tendon elongation (r s =0.74, p=0.05) during the early phase of healing. There was a trend towards positive correlation between MMP-7 and cross-sectional area during the early phase of healing (r s =0.67, p=0.08). Conclusions Patients with a history of Achilles tendon rupture appear to have elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In these pilot data, the view that the MMP–TIMP system is involved in tendinopathy is supported and that disturbances in proteolytic control might be generalised are suggested.
Activation of Parenchymal CD47 Promotes Renal Ischemia-Reperfusion Injury
Authors: Natasha M. Rogers, Angus W. Thomson, Jeffrey S. Isenberg
Journal: Journal of the American Society of Nephrology (2012)

Ischemia-reperfusion injury (IRI) contributes to decreased allograft function and allograft rejection in transplanted kidneys. Thrombospondin-1 is a stress protein typically secreted in response to hypoxia and the ligand activator for the ubiquitously expressed receptor CD47. The function of activated CD47 in IRI remains completely unknown. Here, we found that both CD47 and its ligand thrombospondin-1 were upregulated after renal IRI in mice. CD47-knockout mice were protected against renal dysfunction and tubular damage, suggesting that the development of IRI requires intact CD47 signaling. Chimeric CD47-knockout mice engrafted with wild-type hematopoietic cells had significantly lower serum creatinine and less tubular damage than wild-type controls after IRI, suggesting that CD47 signaling in parenchymal cells predominantly mediates renal damage. Treatment with a CD47-blocking antibody protected mice from renal dysfunction and tubular damage compared with an isotype control. Taken together, these data imply that CD47 on parenchymal cells promotes injury after renal ischemia and reperfusion. Therefore, CD47 blockade may have therapeutic potential to prevent or suppress ischemia-reperfusion-mediated damage.
Expression of individual Ia specificities on T and B cells. I. Studies with mitogen-induced blast cells.
Authors: C David, T Meo, J McCormick, D Shreffler
Journal: The Journal of Experimental Medicine (1976)

Ia specificities 1-10 were detected on LPS-stimulated splenic lymphocytes and on Con A-stimulated spleen, lymph node, and thymus blasts by direct cytotoxic tests. Since Ia antigens are not readily detectable on resting thymocytes, our results suggest that T cells require some signal before they exhibit full expression of Ia specificities. Absorption-elution studies indicated that most of the Ia specificities detected on T and B cells may be identical. Ia antigens detected by homologous antisera gave much stronger reactions than those detected by cross-reacting antisera.
Ascertainment of Patients With Myelodysplastic Syndromes
Authors: Xiaomei Ma, Rong Wang
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: In a recent article published in Journal of Clinical Oncology, Goldberg et al estimated that approximately 45,000 new cases of myelodysplastic syndromes (MDSs) were diagnosed among individuals 65 years or older in the United States in 2003. This number was surprisingly high, given that two other studies have estimated that the number of incident MDS cases is approximately 10,000 each year in the United States, and in both studies, that estimate was reportedly for all age groups combined. After a careful review of the article by Goldberg et al, we were quite concerned about how the authors ascertained MDS patients from among Medicare beneficiaries. As described by the authors, “the International Classification of Diseases for Oncology ninth edition CM (ICD-9-CM) code 238.7 was used to identify patients with a new diagnosis of MDS in calendar year 2003,” and patients with anemias of known causes or myeloid leukemia diagnosed in the previous year (2002) were excluded. It seems that the authors confused two different disease classification systems: the International Classification of Diseases, with the most recent codes contained within the 10th edition, and the International Classification of Diseases for Oncology, with the most recent codes contained within the 3rd edition. The code cited by the authors, 238.7, is an ICD-9-CM code (CM indicates clinical modification) that is not specific to MDS. Rather, it includes multiple other diseases and conditions. The American Medical Association publishes the ICD-9-CM codes annually. In the 2002 and 2003 publications, the following information was listed for code 238.7. 238.7. Other lymphatic and hematopoietic tissues. Disease: lymphoproliferative (chronic), not otherwise specified; myeloproliferative (chronic), not otherwise specified; idiopathic thrombocythemia; megakaryocytic myelosclerosis; myelodysplastic syndrome; myelosclerosis with myeloid metaplasia; panmyelosis (acute). A patient who had Medicare claims that included an ICD-9-CM code of 238.7 might have been diagnosed with MDS or one of the several other diseases or conditions designated by this code. By using a nonspecific diagnostic code, the authors included non-MDS cases in their study population, which inflated the number of MDS patients and made the study findings difficult to interpret.
Treatment of Plasma Cell Dyscrasias With Thalidomide and Its Derivatives
Authors: Meletios A. Dimopoulos, Athanasios Anagnostopoulos, Donna Weber
Journal: Journal of Clinical Oncology (2003)

In 1999, investigators reported promising results of a phase II study of thalidomide in patients with resistant multiple myeloma (MM). Since then, various trials of thalidomide alone and in combination with other agents have been tested in patients with resistant and, more recently, untreated MM. In addition, preliminary results of phase I studies of the immunomodulatory derivatives (IMiDs) of thalidomide have been recently reported.We reviewed and report the results of clinical trials of thalidomide and the IMiDs, as well as the pharmacology, mechanism of action, and toxicity of these agents.Thalidomide has demonstrated significant activity in both resistant and previously untreated multiple myeloma. Combination therapy with dexamethasone increases response rate, even in patients previously resistant to both drugs given as single agents. More recent studies of thalidomide with dexamethasone in previously untreated patients are highly encouraging. The addition of chemotherapy to thalidomide and dexamethasone may further increase response rates, but its effect on patient survival has not been clarified. Preliminary results of trials of IMiD-3 indicate that this agent is active in resistant myeloma and has a toxicity profile different from that of thalidomide.Many studies have confirmed the activity of thalidomide in MM, as well as an improved response with dexamethasone. Newer thalidomide derivatives with reduced toxicity (neuropathy, teratogenicity) are also promising. Thalidomide with dexamethasone may now represent the treatment of choice for previously untreated patients. Further studies with these and other novel agents early in the course of myeloma may improve complete remission rates and frequency of long-term control.
The economy of isometric force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hypothyroid rat myocardium.
Authors: C Holubarsch, R P Goulette, R Z Litten, B J Martin, L A Mulieri, N R Alpert
Journal: Circulation Research (1985)

Hypothyroidism was induced in Wistar-Kyoto rats by adding propylthiouracil to the drinking water (0.8 mg/ml). Initial heat, total activity-related heat, and resting heat rate were measured in left ventricular papillary muscle preparations of propylthiouracil-treated and control rats contracting isometrically at 12 beats/min (21 degrees C), using Hill type, planar vacuum-deposited bismuth and antimony thermopiles. In the propylthiouracil preparations, relative to control, time-to-peak tension increased from 288 +/- 27 (mean +/- SD) to 411 +/- 25 msec (P less than 0.001), dp/dtmax decreased from 38.3 +/- 9.5 to 20.4 +/- 3.5 g X mm-2/sec (P less than 0.001), and peak developed tension decreased from 6.11 +/- 1.75 to 4.64 +/- 0.89 g X mm-2 (P less than 0.05). In the propylthiouracil preparations, initial heat was significantly (P less than 0.001) reduced by 27 or 43% when normalized to peak twitch tension or tension-time integral, respectively. In experiments where the papillary muscles were tetanized, the slope of the linear function of total activity-related heat versus tension-time integral was decreased by 43% (P less than 0.001) in the propylthiouracil preparations, indicating an improved economy of isometric tension maintenance. The predominant myosin isoenzyme of the left ventricular wall, as well as the papillary muscle myocardium, was the V3 variety in the propylthiouracil animals, in contrast to V1 in the controls. Myofibrillar actomyosin calcium-magnesium-stimulated adenosine triphosphatase activity was significantly (P less than 0.02) decreased from 55 +/- 18 (control) to 31 +/- 8 nmol inorganic phosphate ion/mg X min (propylthiouracil).(ABSTRACT TRUNCATED AT 250 WORDS)
Percutaneous Treatment With Drug-Eluting Stent Implantation Versus Bypass Surgery for Unprotected Left Main Stenosis
Authors: Alaide Chieffo, Nuccia Morici, Francesco Maisano, Erminio Bonizzoni, John Cosgrave, Matteo Montorfano, Flavio Airoldi, Mauro Carlino, Iassen Michev, Gloria Melzi, Giuseppe Sangiorgi, Ottavio Alfieri, Antonio Colombo
Journal: Circulation (2006)

Background— Improvements in results with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may extend their use in patients with left main coronary artery (LMCA) stenosis. Methods and Results— Two hundred forty-nine patients with LMCA stenosis were treated with PCI and DES implantation (n=107) or coronary artery bypass grafting (CABG) (n=142), in a single center, between March 2002 and July 2004. A propensity analysis was performed to adjust for baseline differences between the two cohorts. At 1 year, there was no statistical difference in the occurrence of death in PCI versus CABG both for the unadjusted (OR=0.291; 95% CI=0.054 to 1.085; P =0.0710) and adjusted analyses (OR=0.331; 95% CI=0.055 to 1.404; P =0.1673). PCI was correlated to a lower occurrence of the composite end points of death and myocardial infarction (unadjusted OR=0.235; 95% CI=0.048 to 0.580; P =0.0002; adjusted OR=0.260; 95% CI=0.078 to 0.597; P =0.0005) and death, myocardial infarction, and cerebrovascular events (unadjusted OR=0.300; 95% CI=0.102 to 0.617; P =0.0004; adjusted OR=0.385; 95% CI=0.180 to 0.819; P =0.01). No difference was detected in the occurrence of major adverse cardiac and cerebrovascular event at the unadjusted (OR=0.675; 95% CI=0.371 to 1.189; P =0.1891) and adjusted analyses (OR=0.568; 95% CI=0.229 to 1.344; P =0.2266). Conclusions— At 1 year, in this single-center, retrospective experience, there was no difference in the degree of protection against death, stroke, myocardial infarction, and revascularization between PCI with DES and CABG for LMCA disease. (Circulation. 2006;113:2542-2547.)
NCI Image-Guided Drug Delivery Summit
Authors: Pushpa Tandon, Keyvan Farahani
Journal: Cancer Research (2011)

On April 17, 2010, scientists from academia, the National Cancer Institute (NCI), and the Food and Drug Administration (FDA) assembled at "The NCI Image Guided Drug Delivery Summit," in Washington D.C., to discuss recent advances, barriers, opportunities, and regulatory issues related to the field. The meeting included a scientific session and an NCI/FDA session, followed by a panel discussion of speakers from both sessions. Image-guided drug delivery (IGDD) in cancer is a form of individualized therapy where imaging methods are used in guidance and monitoring of localized and targeted delivery of therapeutics to the tumor. So, a systematic approach to IGDD requires mechanisms for targeting, delivery, activation, and monitoring of the process. Although the goal in IGDD is to optimize the therapeutic ratio through personalized image-guided treatments, a major challenge is in overcoming the biological barriers to the delivery of therapeutics into tumors and cells. Speakers discussed potential challenges to clinical translation of nano-based drug delivery systems including in vivo characterization of nanocarriers, preclinical validation of targeting and delivery, studies of biodistribution, pharmacokinetics, pharmacodynamics, and toxicity as well as scale-up manufacturing of delivery systems. Physiologic and quantitative imaging techniques may serve as enabling tools that could potentially transform many existing challenges into opportunities for advancement of the field.