tbuckley/cabot-search huggingface dataset:
A Novel Role for the Coxsackie Adenovirus Receptor in Mediating Tumor Formation by Lung Cancer Cells
Authors: Min Qin, Brian Escuadro, Mariam Dohadwala, Sherven Sharma, Raj K. Batra
Journal: Cancer Research (2004)

Abstract The Coxsackie Adenovirus Receptor (CAR) has primarily been studied in its role as the initial cell surface attachment receptor for Coxsackie and group C adenoviruses. Recent reports suggest that CAR mediates homotypic intercellular adhesion as part of the tight and/or adherens junction. Thus, CAR is well positioned to participate in intercellular interactions and signaling. Using an antisense (AS)-CAR plasmid vector, we silenced surface CAR expression in lung cancer cells that possessed a high basal expression of this molecule and monitored the resultant tumorigenesis. AS-CAR transfectants exhibit a profound loss in the ability to generate xenografts in scid/scid mice. The emergence of delayed-onset tumors in animals that received injection with AS-CAR transfectants correlates with the resurfacing of CAR expression, suggesting that such expression and tumor emergence are temporally related. To study the mechanism underlying the differences in tumorigenicity, control and AS-CAR cells were compared in terms of their in vitro growth potential. Whereas only subtle differences in the proliferative capacity of the two populations were evident when assayed with growth on plastic, significant differences became apparent when one compared the relative ability of these populations to form colonies in soft agar. These data indicate that silencing surface CAR expression abrogates xenograft tumorigenesis in vivo and colony formation in vitro and invoke the novel possibility that CAR expression is needed for the efficient formation of tumors by a subset of lung cancer cells.
Mechanism by which hyperglycemia inhibits hepatic glucose production in conscious rats. Implications for the pathophysiology of fasting hyperglycemia in diabetes.
Authors: L Rossetti, A Giaccari, N Barzilai, K Howard, G Sebel, M Hu
Journal: Journal of Clinical Investigation (1993)

To examine the relationship between the plasma glucose concentration (PG) and the pathways of hepatic glucose production (HGP), five groups of conscious rats were studied after a 6-h fast: (a) control rats (PG = 8.0 +/- 0.2 mM); (b) control rats (PG = 7.9 +/- 0.2 mM) with somatostatin and insulin replaced at the basal level; (c) control rats (PG = 18.1 +/- 0.2 mM) with somatostatin, insulin replaced at the basal level, and glucose infused to acutely raise plasma glucose by 10 mM; (d) control rats (PG = 18.0 +/- 0.2 mM) with somatostatin and glucose infusions to acutely reproduce the metabolic conditions of diabetic rats, i.e., hyperglycemia and moderate hypoinsulinemia; (e) diabetic rats (PG = 18.4 +/- 2.3 mM). All rats received an infusion of [3-3H]glucose and [U-14C]lactate. The ratio between hepatic [14C]UDP-glucose sp act (SA) and 2X [14C]-phosphoenolpyruvate (PEP) SA (the former reflecting glucose-6-phosphate SA) measured the portion of total glucose output derived from PEP-gluconeogenesis. In control rats, HGP was decreased by 58% in hyperglycemic compared to euglycemic conditions (4.5 +/- 0.3 vs. 10.6 +/- 0.2 mg/kg.min; P < 0.01). When evaluated under identical glycemic conditions, HGP was significantly increased in diabetic rats (18.9 +/- 1.4 vs. 6.2 +/- 0.4 mg/kg.min; P < 0.01). In control rats, hyperglycemia increased glucose cycling (by 2.5-fold) and the contribution of gluconeogenesis to HGP (91% vs. 45%), while decreasing that of glycogenolysis (9% vs. 55%). Under identical plasma glucose and insulin concentrations, glucose cycling in diabetic rats was decreased (by 21%) and the percent contribution of gluconeogenesis to HGP (73%) was similar to that of controls (84%). These data indicate that: (a) hyperglycemia causes a marked inhibition of HGP mainly through the suppression of glycogenolysis and the increase in glucokinase flux, with no apparent changes in the fluxes through gluconeogenesis and glucose-6-phosphatase; under similar hyperglycemic hypoinsulinemic conditions: (b) HGP is markedly increased in diabetic rats; however, (c) the contribution of glycogenolysis and gluconeogenesis to HGP is similar to control animals.
Novel Myofilament Ca <sup>2+</sup> -Sensitizing Property of Xanthine Oxidase Inhibitors
Authors: Néstor Gustavo Pérez, Wei Dong Gao, Eduardo Marbán
Journal: Circulation Research (1998)

Abstract —Antioxidants are known to mitigate the cardiac contractile dysfunction that follows brief periods of ischemia (“myocardial stunning”). Stunning decreases contractility at the level of the contractile proteins; therefore, we asked whether antioxidant treatment preserves myofilament Ca 2+ responsiveness after global ischemia and reflow. Right ventricular trabeculae were dissected from rat hearts subjected either to 20 minutes ischemia and reperfusion in the absence of drugs (stunned group) or to the same protocol in the presence of allopurinol, an inhibitor of xanthine oxidase (XO), and mercaptopropionylglycine (MPG), a hydroxyl radical scavenger (antioxidant group). At 20 minutes of reflow, isovolumic developed pressure recovered completely in the antioxidant group, but in the stunned group it recovered by only 57%. [Ca 2+ ] i and contractile force measurements in trabeculae revealed the expected depression of myofilament function in the stunned group, with no change in Ca 2+ transients relative to nonischemic controls. In contrast, Ca 2+ transients were smaller, but force was greater, in the antioxidant group relative to both the stunned group and to nonischemic controls. Steady-state [Ca 2+ ] i -force relationships revealed a striking increase of maximal force and a modest shift of activation to a lower range of [Ca 2+ ] i . The increase in maximal force was reproduced by allopurinol+MPG or by allopurinol alone under nonischemic conditions and also by oxypurinol (100 μmol/L), a potent inhibitor of XO. We conclude that allopurinol and oxypurinol sensitize the cardiac myofilaments to Ca 2+ . This Ca 2+ -sensitizing effect underlies the preservation of contractility observed with an allopurinol+MPG antioxidant cocktail in a model of stunned myocardium. These serendipitous findings identify allopurinol and oxypurinol as the lead compounds of a novel class of inotropic agents.
Disparity between ultrasound and clinical findings in psoriatic arthritis
Authors: Rusmir Husic, Judith Gretler, Anja Felber, Winfried B Graninger, Christina Duftner, Josef Hermann, Christian Dejaco
Journal: Annals of the Rheumatic Diseases (2013)

To investigate the association between psoriatic arthritis (PsA)-specific clinical composite scores and ultrasound-verified pathology as well as comparison of clinical and ultrasound definitions of remission.We performed a prospective study on 70 consecutive PsA patients. Clinical assessments included components of Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI). Minimal disease activity (MDA) and the following remission criteria were applied: CPDAI joint, entheses and dactylitis domains (CPDAI-JED)=0, DAPSA≤3.3, Boolean's remission definition and physician-judged remission (rem-phys). B-mode and power Doppler (PD-) ultrasound findings were semiquantitatively scored at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Ultrasound remission and minimal ultrasound disease activity (MUDA) were defined as PD-score=0 and PD-score ≤1, respectively, at joints, peritendinous tissue, tendons and entheses.DAPSA but not CPDAI correlated with B-mode and PD-synovitis. Ultrasound signs of enthesitis, dactylitis, tenosynovitis and perisynovitis were not linked with clinical composites. Clinical remission or MDA was observed in 15.7% to 47.1% of PsA patients. Ultrasound remission and MUDA were present in 4.3% and 20.0% of patients, respectively. Joint and tendon-related PD-scores were higher in patients with active versus inactive disease according to CPDAI-JED, DAPSA, Boolean's and rem-phys, whereas no difference was observed regarding enthesitis and perisynovitis. DAPSA≤3.3 (OR 3.9, p=0.049) and Boolean's definition (OR 4.6, p=0.03) were more useful to predict MUDA than other remission criteria.PsA-specific composite scores partially reflect ultrasound findings. DAPSA and Boolean's remission definitions better identify MUDA patients than other clinical criteria.
Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure
Authors: M. L. A. Schuttelaar, M. Kerkhof, M. F. Jonkman, G. H. Koppelman, B. Brunekreef, J. C. De Jongste, A. Wijga, W. H. I. McLean, D. S. Postma
Journal: Allergy (2009)

Background: Filaggrin gene ( FLG ) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear. Methods: FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort ( n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure. Results: The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4–2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8–7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early‐life cat exposure (ORs being 8.2; 95% CI: 2.6–25.9, 6.0; 95% CI: 3.2–11.3 and 5.4; 95% CI: 1.2–23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5–10.5). Conclusions: FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization.
Vascular Imaging of Solid Tumors in Rats with a Radioactive Arsenic-Labeled Antibody that Binds Exposed Phosphatidylserine
Authors: Marc Jennewein, Matthew A. Lewis, Dawen Zhao, Edward Tsyganov, Nikolai Slavine, Jin He, Linda Watkins, Vikram D. Kodibagkar, Sean O'Kelly, Padmakar Kulkarni, Peter P. Antich, Alex Hermanne, Frank Rösch, Ralph P. Mason, Philip E. Thorpe
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats. Experimental Design: Bavituximab was labeled with 74As (β+, T1/2 17.8 days) or 77As (β−, T1/2 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1 tumors in rats. Results: Clear images of the tumors were obtained using planar γ-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium. Conclusions: These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.
Impact of elevated heart rate on clinical outcomes in patients with heart failure with reduced and preserved ejection fraction: a report from the <scp>CHART</scp>‐2 Study
Authors: Tsuyoshi Takada, Yasuhiko Sakata, Satoshi Miyata, Jun Takahashi, Kotaro Nochioka, Masanobu Miura, Soichiro Tadaki, Hiroaki Shimokawa
Journal: European Journal of Heart Failure (2013)
Cellular and molecular requirements for X-linked, hapten-specific B-cell blockade in CBA/N mice.
Authors: B Merchant, H Snippe, E F Lizzio, J K Inman
Journal: The Journal of Experimental Medicine (1978)

CBA/N mice, a mutant CBA subline, harbor an X-linked B-cell defect which prevents them from mounting immune responses to certain thymic-independent antigens such as pneumococcal polysaccharides and haptenated-Ficoll derivatives. These mice and the hybrid male progeny of CBA/N females are also exquisitely sensitive to a hapten-specific blockade of their otherwise adequate immune responses to thymic-dependent antigens such as N-2,4-dinitrophenylated-hemocyanin (DNP-KLH). As little as 10 ng of a DNP-Ficoll conjugate given 2 h before immunization with a 5,000-fold greater dosage of DNP-KLH, virtually abolishes the 4th-day direct plaque-forming cell (PFC) response specific for DNP. Responding hybrid (CBA/N x C3H/HeN) female mice are resistant to such blockade even at DNP-Ficoll dosages increased by three orders of magnitude. The DNP hapten and Ficoll must be chemically joined for this blocking effect to occur, and increasing the hapten derivatization of Ficoll increases its blockade-invoking capacity. Significant blockade can be produced by administering DNP-Ficoll as early as 4 days before or as late as 4 h after immunization with DNP-KLH. All currently available data point to the defective B cell as the target of this hapten-polysaccharide-mediated blockade. Mice bearing B memory cells, however, are refractory to such blockade. In addition, DNP-Ficoll injections which cause virtually total blockade of 4th-day primary direct PFC responses to DNP-KLH have little or no effect on the development of DNP-reactive B-cell memory measured at either 8 or 30 days. These findings suggest very different blockade susceptibilities for B cells or their precursors at various stages of differentiative development. Our findings also lead to the formulation of testable hypotheses regarding the mechanism of this selective B-cell blockade phenomenon.
Aggressive extracorporeal shock wave lithotripsy of gall bladder stones within wider treatment criteria: fragmentation rate and early results.
Authors: G Meiser, M Heinerman, G Lexer, O Boeckl
Journal: Gut (1992)

Two hundred and twenty patients with a total of 412 gall bladder stones of between 8 and 38 mm in size were treated with extracorporeal shock wave lithotripsy, using the overhead module Lithostrar Plus. Fifty six per cent of stones were solitary (mean (SD) diameter 23 (5) mm) and 9.5% of the patients had more than three stones. Stones were successfully disintegrated in 218 patients (fragmentation size less than 5 mm in 80%, less than 10 mm in 19%). Some 65% of patients required one treatment and the rest two or three. A mean (SD) of 4100 (1800) shock waves with a pressure of 700 bar were applied. Twenty four to 48 hours after lithotripsy a transient but significant increase in serum transaminase activities (31%) and in bilirubin (29%), urinary amylase (27%), and blood leukocyte (62%) values was observed. In 29% of patients there was a transient microhaematuria, in 2% transient macrohaematuria, and in 25% painless petechiae of the skin. Ultrasound showed temporary gall bladder wall oedema in 13%, temporary distension of the gall bladder in 11%, and transient common bile duct distension in 8% after treatment. After discharge from hospital, 31% of patients complained of recurrent colic that responded to simple analgesics. Four to eight weeks after therapy, four patients developed biliary pancreatitis and 11 biliary obstruction that was managed by endoscopy. To date, 105 patients have been followed for over 12 months. Sixty one of these had a solitary stone, 17 had two, and 27 had three or more stones. A total of 59 patients, including 44 with a primary solitary stone, eight with two stones, and seven with three or more stones are completely stone free.
Management of interleukin-2-induced severe bronchoconstriction
Authors: T. Suda, H. Hashizume, Y. Aoshima, K. Yokomura, J. Sato, N. Inui, Y. Nakamura, T. Fujisawa, N. Enomoto, K. Chida
Journal: European Respiratory Journal (2007)

To the Editors: 

The immunostimulatory cytokine, interleukin (IL)-2, is used for the treatment of patients with cancers, such as metastatic renal cell carcinoma and melanoma 1, 2. The toxicity of IL-2 has been well described, including hypotension, a capillary leak syndrome including pulmonary oedema, thrombocytopenia and renal dysfunction 1, 3–5. Interestingly in a rare case, IL-2 administration, especially its inhalation, was reported to cause bronchoconstriction 3, 4, 6. However, little is known about the risk factors and management of IL-2-induced bronchoconstriction. We conducted a study to elucidate the clinical characteristics of patients developing IL-2-induced bronchoconstriction and to examine how to manage this condition.

The study subjects included 18 patients with malignant cutaneous haemangioendothelioma (10 males and 8 females). Most of them were elderly with a mean (range) age of 72.3 (52–95) yrs, and all had lesions on the face and head. All patients received IL-2 immunotherapy plus radiotherapy. IL-2 was administered intralesionally in four patients and …
Challenges in Colorectal Cancer
Authors: M. Pai, R. Canelo
Journal: Gut (2007)

Edited by John H Scholefield, Herand Abcarian, Axel Grothey, Tim Maughan. Oxford: Blackwell Publishing, 2006, £69.50, pp 296. ISBN 9781405127066.

Colorectal adenocarcinoma (colorectal cancer; CRC) is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Almost 1 million new cases of CRC occur annually, amounting to 492 000 related deaths. In developed countries, it is the second most common type of tumour, with a lifetime risk of …
What do patients receiving palliative care for cancer and their families want to be told? A Canadian and Australian qualitative study
Authors: Peter Kirk, Ingrid Kirk, Linda J Kristjanson
Journal: BMJ (2004)

<b>Objective</b> To obtain feedback from patients receiving palliative care and their relatives from various ethnic backgrounds about their experiences of the disclosure process and their satisfaction with information sharing during the illness. <b>Design</b> A qualitative study with semistructured single interviews. <b>Setting</b> Perth, Western Australia, and Winnipeg, Manitoba, Canada. <b>Participants</b> 72 participants registered with palliative care: 21 patient-family dyads in Perth and 14 dyads and 2 patients in Winnipeg. <b>Results</b> Participants described their experiences in great detail. The analysis indicates that in information sharing the process is as important as the content. The timing, management, and delivery of information and perceived attitude of practitioners were critical to the process. This applied to information interactions at all stages of the illness. Main content areas mentioned related to prognosis and hope. Hope can be conveyed in different ways. Secondary information from various sources is accessed and synthesised with the primary information. All patients, regardless of origin, wanted information about their illness and wanted it fully shared with relatives. Almost all patients requested prognostic information, and all family members respected their wishes. Information was perceived as important for patient-family communication. Information needs of patient and family changed and diverged as illness progressed, and communication between them became less verbally explicit. <b>Conclusions</b> Information delivery for patients needs to be individualised with particular attention to process at all stages of illness. Patients and families use secondary sources of information to complement and verify information given by health carers.
Nestin-Linked Green Fluorescent Protein Transgenic Nude Mouse for Imaging Human Tumor Angiogenesis
Authors: Yasuyuki Amoh, Meng Yang, Lingna Li, Jose Reynoso, Michael Bouvet, Abdool R. Moossa, Kensei Katsuoka, Robert M. Hoffman
Journal: Cancer Research (2005)

Abstract We report here a novel transgenic nude mouse for the visualization of human tumor angiogenesis. We have recently shown that the neural stem cell marker nestin is expressed in hair follicle stem cells and blood vessel networks in the skin of C57/B6 transgenic mice with nestin regulatory element–driven green fluorescent protein (ND-GFP). Others have shown ND-GFP is expressed in the brain, pancreas, and testes in these mice. In the present study, the nestin ND-GFP gene was crossed into nude mice on the C57/B6 background to obtain ND-GFP nude mice. ND-GFP was expressed in the brain, spinal cord, pancreas, stomach, esophagus, heart, lung, blood vessels of glomeruli, blood vessels of skeletal muscle, testes, hair follicles, and blood vessel network in the skin of ND-GFP nude mice. Human lung cancer, pancreatic cancer, and colon cancer cell lines as well as a murine melanoma cell line and breast cancer tumor cell line expressing red fluorescent protein were implanted orthotopically, and a red fluorescent protein–expressing human fibrosarcoma was implanted s.c. in the ND-GFP nude mice. These tumors grew extensively in the ND-GFP mice. ND-GFP was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumors, visualized by dual-color fluorescence imaging. Results of immunohistochemical staining showed that CD31 was expressed in the ND-GFP–expressing nascent blood vessels. The ND-GFP transgenic nude mouse model enables the visualization of nascent angiogenesis in human and mouse tumor progression. These results suggest that this model is useful for the imaging of the angiogenesis of human as well as rodent tumors and visualization of the efficacy of angiogenetic inhibitors.
Haemopericardium and cardiac tamponade complicating pulmonary lymphangioleiomyomatosis.
Authors: J Fahy, M Toner, J O'Sullivan, M X FitzGerald
Journal: Thorax (1991)

The outcome of dendritic cell (DC) presentation of tumor and/or self peptides, including P815AB (a tumor peptide of murine mastocytoma cells) and NRP-A7 (a synthetic peptide mimotope recognized by diabetogenic T cells), may depend on a balance between the activities of immunogenic (CD8α<sup>−</sup>) and tolerogenic (CD8α<sup>+</sup>) DC. By virtue of their respective actions on CD8<sup>−</sup> and CD8<sup>+</sup> DC, IL-12 and IFN-γ have functionally opposing effects on peptide presentation by the CD8<sup>−</sup> DC subset, and IFN-γ-activated CD8<sup>+</sup> DC mediate tolerogenic effects that prevail over the adjuvant activity of IL-12 on CD8<sup>−</sup> DC. We have previously shown that CD40 ligation abrogates the tolerogenic potential of CD8<sup>+</sup> DC, an effect associated with an impaired capacity of the CD40-modulated and IFN-γ-treated DC to degrade tryptophan and initiate T cell apoptosis in vitro. We report here that IL-6 may both replace (upon administration of the recombinant cytokine) and mediate (as assessed by the use of neutralizing Abs) the effect of CD40 ligation in ablating the tolerogenic activity of CD8<sup>+</sup> DC. The activity of IL-6 includes down-regulation of IFN-γR expression in the CD8<sup>+</sup> DC subset and correlates to a reduced ability of these cells to metabolize tryptophan and initiate T cell apoptosis in vitro.