tbuckley/cabot-search huggingface dataset:
Inhibition of VEGFR-3 Activation with the Antagonistic Antibody More Potently Suppresses Lymph Node and Distant Metastases than Inactivation of VEGFR-2
Authors: Nicole Roberts, Bryan Kloos, Melanie Cassella, Simona Podgrabinska, Kris Persaud, Yan Wu, Bronislaw Pytowski, Mihaela Skobe
Journal: Cancer Research (2006)

Abstract Lymph nodes are the first site of metastases for most types of cancer, and lymph node status is a key indicator of patient prognosis. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) has been shown to play an important role in promoting tumor metastases to lymph nodes. Here, we employed receptor-specific antagonist antibodies in an orthotopic spontaneous breast cancer metastasis model to provide direct evidence for the key role of VEGFR-3 activation in metastasis. Inhibition of VEGFR-3 activation more potently suppressed regional and distant metastases than inactivation of VEGFR-2, although VEGFR-2 blockade was more effective in inhibiting angiogenesis and tumor growth. Despite prominent proliferation, metastases were not vascularized in any of the control and treatment groups, indicating that the growth of metastases was not dependent on angiogenesis at the secondary site for the duration of the experiment. Systemic treatment with either VEGFR-2 or VEGFR-3 antagonistic antibodies suppressed tumor lymphangiogenesis, indicating that VEGFR-3 signaling affects the rate of tumor cell entry into lymphatic vessels through both lymphangiogenesis-dependent and independent mechanisms. Combination treatment with the anti-VEGFR-2 and anti-VEGFR-3 antibodies more potently decreased lymph node and lung metastases than each antibody alone. These results validate the concept of targeting the lymphatic dissemination and thereby very early steps of the metastatic process for metastasis control and suggest that a combination therapy with antiangiogenic agents may be a particularly promising approach for controlling metastases. (Cancer Res 2006; 66(5): 2650-7)
Measurement of duodenal tryptic activity and 75Se-selenomethionine pancreatic scanning compared as tests of pancreatic function
Authors: D. M. McCarthy, P. Brown
Journal: Gut (1969)

The results of a subjective assessment of pancreatic function, based on the appearance of a <sup>75</sup>Se-pancreatic scan, were compared with measurements of the tryptic activity of duodenal aspirates in 16 normal and 38 abnormal subjects. In normals and in abnormals whose scans showed a generalized rather than a localized abnormality there was close agreement between the results of the two sets. In patients with a localized abnormality of the pancreatic head on scanning the tryptic activity of the aspirate was useful in differentiating carcinoma of the pancreas from that of the common bile duct. In general the scan was the more discriminative test though otherwise the places of the two tests in diagnosis are rather similar. The particular situations in which each test is valuable, or in which one or other test can be omitted, are discussed.
Tim-2 regulates T helper type 2 responses and autoimmunity
Authors: Sumone Chakravarti, Catherine A. Sabatos, Sheng Xiao, Zsolt Illes, Eugene K. Cha, Raymond A. Sobel, Xin X. Zheng, Terry B. Strom, Vijay K. Kuchroo
Journal: The Journal of Experimental Medicine (2005)

Identification of the T cell immunoglobulin mucin-domain containing (Tim) gene family introduced a new family of cell surface molecules that is involved in the regulation of immune responses. We previously demonstrated that Tim-3 is expressed on terminally differentiated T helper (Th)1 cells, and serves to regulate Th1 immune responses. Here, we describe the identification and function of Tim-2, a novel member of the Tim gene family. In contrast with Tim-3, we demonstrate that Tim-2 is expressed preferentially in differentiated Th2 cells. Blockade of the Tim-2/Tim-2 ligand interaction, by administration of soluble Tim-2 fusion protein (Tim-2 immunoglobulin [Ig]), results in T cell hyperproliferation and the production of Th2 cytokines. Administration of Tim-2 Ig during the induction phase reduces the severity of experimental autoimmune encephalomyelitis, a Th1-mediated autoimmune disease model of multiple sclerosis. We propose that Tim-2, an orthologue of human Tim-1, is critical for the regulation of Th2 responses during autoimmune inflammation.
Effect of S-adenosylmethionine on neointimal formation after balloon injury in obese diabetic rats
Authors: Soo Lim, Min Kyong Moon, Hayley Shin, Tae Hyuk Kim, Bong Jun Cho, Min Kim, Ho Seon Park, Sung Hee Choi, Seong-Hee Ko, Myung Hee Chung, In Kyu Lee, Hak Chul Jang, Young-Bum Kim, Kyong Soo Park
Journal: Cardiovascular Research (2011)

The association between hyperhomocysteinaemia and cardiovascular disease has been attributed to low levels of S-adenosylmethionine (SAM), a metabolic intermediate of homocysteine. However, the role of SAM in the development of restenosis has not been explored. Therefore, we investigated the effects of SAM on neointimal formation after balloon injury in obese diabetic rats and cultured cells.Otsuka Long-Evans Tokushima fatty rats were divided into the following three groups: control (normal saline); SAM15; and SAM30 (15 and 30 mg/kg per day, respectively; n = 10 per group). SAM was administered orally from 1 week before carotid injury to 2 weeks thereafter. SAM treatment for 3 weeks caused a significant dose-dependent reduction in the intima-to-media ratio. SAM treatment significantly reduced the proliferation of vascular smooth muscle cells (VSMCs) and induced more apoptosis than was observed in the control group. This effect was accompanied by reduced circulating levels of high-sensitivity C-reactive protein and monocyte chemoattractant protein-1, reduced urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), and increased adiponectin. Intima-to-media ratio correlated significantly with the levels of inflammatory markers, adiponectin, and 8-OHdG. In vitro experiments demonstrated that VSMC proliferation and migration and the adhesion of monocytes decreased in response to SAM. SAM treatment also reduced tumour necrosis factor-α-induced reactive oxygen species and tunicamycin-induced GRP78 expression in VSMCs.These findings suggest that SAM exerts protective effects against restenosis after balloon injury in a rat model of type 2 diabetes by reducing the proliferation and inducing the apoptosis of VSMCs, modifying the inflammatory processes and reducing oxidative and endoplasmic reticulum stresses.
Cell surface antigens of human malignant melanoma. III. Recognition of autoantibodies with unusual characteristics.
Authors: H Shiku, T Takahashi, L A Resnick, H F Oettgen, L J Old
Journal: The Journal of Experimental Medicine (1977)

The sera of three patients with malignant melanoma showing reactivity with surface antigens of cultured autologous melanoma cells were analyzed by mixed hemadsorption and immune adherence assays in conjunction with absorption tests. In contrast to the melanoma-specific antigens demonstrated previously, the surface antigens detected by these sera occurred on a broad range of nucleated cells, both normal and malignant, from human, monkey, mouse, and chicken sources. Each serum had a characteristic pattern of reactivity in absorption tests, indicating the detection of distinct antigenic systems. Two sera showed auto-, allo-, and xenoreactivity, as well as the capacity to distinguish different cell populations in the same individual. The other serum reacted with an antigen apparently universally present on nucleated cells from a variety of species, but absent on erythrocytes. As these patients had been treated with chemotherapy, this may have played a role in the emergence of these broadly reactive autoantibodies.
Publication guidelines for quality improvement studies in health care: evolution of the SQUIRE project
Authors: F. Davidoff, P. Batalden, D. Stevens, G. Ogrinc, S. E Mooney
Journal: BMJ (2009)

In 2005 we published draft guidelines for reporting studies of quality improvement, as the initial step in a consensus process for development of a more definitive version. The current article contains the revised version, which we refer to as standards for quality improvement reporting excellence (SQUIRE). This narrative progress report summarises the special features of improvement that are reflected in SQUIRE, and describes major differences between SQUIRE and the initial draft guidelines. It also briefly describes the guideline development process; considers the limitations of and unresolved questions about SQUIRE; describes ancillary supporting documents and alternative versions under development; and discusses plans for dissemination, testing, and further development of SQUIRE.
An overview of randomized trials of rehabilitation with exercise after myocardial infarction.
Authors: G T O'Connor, J E Buring, S Yusuf, S Z Goldhaber, E M Olmstead, R S Paffenbarger, C H Hennekens
Journal: Circulation (1989)

Of 22 randomized trials of rehabilitation with exercise after myocardial infarction (MI), one trial had results that achieved conventional statistical significance. To determine whether or not these studies, in the aggregate, show a significant benefit of rehabilitation after myocardial infarction, we performed an overview of all randomized trials, involving 4,554 patients; we evaluated total and cardiovascular mortality, sudden death, and fatal and nonfatal reinfarction. For each endpoint, we calculated an odds ratio (OR) and 95% confidence interval (95% CI) for the trials combined. After an average of 3 years of follow-up, the ORs were significantly lower in the rehabilitation than in the comparison group: specifically, total mortality (OR = 0.80 [0.66, 0.96]), cardiovascular mortality (OR = 0.78 [0.63, 0.96]), and fatal reinfarction (OR = 0.75 [0.59, 0.95]). The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year (OR = 0.63 [0.41, 0.97]). The data were compatible with a benefit at 2 (OR = 0.76 [0.54, 1.06]) and 3 years (OR = 0.92 [0.69, 1.23]), but these findings were not statistically significant. For nonfatal reinfarction, there were no significant differences between the two groups after 1 (OR = 1.09 [0.76, 1.57]), 2 (OR = 1.10 [0.82, 1.47]), or 3 years (OR = 1.09 [0.88, 1.34]) of follow-up. The observed 20% reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfarction throughout at least 3 years and a reduction in sudden death during the 1st year after infarction and possibly for 2-3 years. With respect to the independent effects of the physical exercise component of cardiac rehabilitation, the relatively small number of "exercise only" trials, combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion. To do so would require a randomized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview.
Cell-ELISA detection of antineuronal antibodies in central nervous system involvement in systemic lupus erythematosus
Authors: X. Zhang, H. Shu, F. Zhang, X. Tian, Y. Dong
Journal: Annals of the Rheumatic Diseases (2006)

To develop a cell-ELISA method to detect antineuronal antibodies (anti-Ns) and evaluate the diagnostic value of anti-Ns in central nervous system involvement in systemic lupus erythematosus (CNS-SLE).Anti-N was assessed in both serum and cerebrospinal fluid (CSF) samples from 38 patients with CNS-SLE, 29 with SLE without CNS involvement (non-CNS-SLE), 36 with other rheumatic diseases and 59 with non-rheumatic diseases with the CNS manifestations using a cell-ELISA method with 1% paraformaldehyde-fixed SK-N-MC neuroblastoma cells as substrate. Serum samples from 37 healthy donors were also included in this study. Patients with CNS-SLE who were anti-N positive in CSF were studied serially for CSF anti-N levels at times of treatment-associated improvement in CNS symptoms.Serum anti-N levels were significantly increased in patients with SLE compared with other groups, with a sensitivity of 61.2% (41/67) and a specificity of 91.8% (p<0.001). CSF anti-N levels were significantly increased in patients with CNS-SLE, with a sensitivity of 47.4% (18/38) and a specificity of 89.7%, whereas only 10.3% (3/29) of patients with non-CNS-SLE had increased anti-N in CSF (p<0.001). CSF anti-N levels decreased significantly after effective treatment of CNS-SLE (p<0.05).Serum anti-N is relatively specific to SLE. CSF anti-N is a sensitive and relatively specific antibody in diagnosing CNS-SLE and correlates with CNS-SLE activity.
Cognitive Functioning of Long-term Heavy Cannabis Users Seeking Treatment
Authors: Nadia Solowij
Journal: JAMA (2002)

DEBATEabout marijuana laws and interest in marijuana as medicine, 1 one issue remains unresolved: Does heavy, frequent, or prolonged use of cannabis lead to a deterioration in cognitive function that persists well beyond any period of acute intoxication?Is the functioning of the brain altered in the long term?With over 7 million people using cannabis weekly or more often in the United States alone 2 and the potential for increased physician recommendations for select patients to use cannabis therapeutically, 1 answers to these questions are of significant public health concern. 3,4 Scientific evidence from past research clearly showed that gross impairment related to chronic cannabis use did not occur but was inconclusive with regard to the presence of more specific deficits. 5,6 Recent studies with improved methods have demonstrated changes in cognition and brain function associated with longterm or frequent use of cannabis.Specific impairments of attention, memory, and executive function have been found in cannabis users in the unintoxicated state (and in children exposed to cannabis in utero 7 ) in controlled studies using brain event-related potential techniques 6,8-10 and neuropsychological assessments 11-15 including complex tasks.7][18][19] Studies failing to detect cognitive decline associated with cannabis use 20 may reflect insufficient heavy or chronic use of cannabis in the sample or the use of insensitive assessment instruments.Impairments appear to increase with duration and frequency of cannabis use; how-ever, the parameters of use that are associated with short-or long-lasting cognitive and brain dysfunction have not
A Method for Accurate Inference of Population Size from Serially Sampled Genealogies Distorted by Selection
Authors: B. D. O'Fallon
Journal: Molecular Biology and Evolution (2011)

The serial coalescent extends traditional coalescent theory to include genealogies in which not all individuals were sampled at the same time. Inference in this framework is powerful because population size and evolutionary rate may be estimated independently. However, when the sequences in question are affected by selection acting at many sites, the genealogies may differ significantly from their neutral expectation, and inference of demographic parameters may become inaccurate. I demonstrate that this inaccuracy is severe when the mutation rate and strength of selection are jointly large, and I develop a new likelihood calculation that, while approximate, improves the accuracy of population size estimates. When used in a Bayesian parameter estimation context, the new calculation allows for estimation of the shape of the pairwise coalescent rate function and can be used to detect the presence of selection acting at many sites in a sequence. Using the new method, I investigate two sets of dengue virus sequences from Puerto Rico and Thailand, and show that both genealogies are likely to have been distorted by selection.
Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency
Authors: William A Irwin, Natascha Bergamin, Patrizia Sabatelli, Carlo Reggiani, Aram Megighian, Luciano Merlini, Paola Braghetta, Marta Columbaro, Dino Volpin, Giorgio M Bressan, Paolo Bernardi, Paolo Bonaldo
Journal: Nature Genetics (2003)
Fix what's wrong, not what's right, with general practice in Britain
Authors: J. De Maeseneer
Journal: BMJ (2000)

The effect of smoking three cigarettes over a one-hour period on the pentagastrinstimulated submaximal plateau of acid and pepsin secretion was observed in 12 healthy human volunteers comprising men and women and smokers and non-smokers. No significant overall change in secretion was observed. In one subject, however, acid secretion was significantly inhibited (p &lt; 0·01) and in one individual significant late stimulation (p &lt; 0·01) of both acid and pepsin was observed.
Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life activities
Authors: M Miravitlles, J B Soriano, F Garcia-Rio, L Munoz, E Duran-Tauleria, G Sanchez, V Sobradillo, J Ancochea
Journal: Thorax (2009)

<h3>Aims:</h3> This study aimed to determine the prevalence of chronic obstructive pulmonary disease (COPD) in Spain and identify the level of undiagnosed disease and its impact on health-related quality of life (HRQL) and activities of daily living (ADL). <h3>Methods:</h3> A population-based sample of 4274 adults aged 40–80 years was surveyed. They were invited to answer a questionnaire and undergo prebrochodilator and postbronchodilator spirometry. COPD was defined as a postbronchodilator FEV<sub>1</sub>/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio of &lt;0.70. <h3>Results:</h3> For 3802 participants with good-quality postbronchodilator spirometry, the overall prevalence of COPD was 10.2% (95% CI 9.2% to 11.1%) and was higher in men (15.1%) than in women (5.6%). The prevalence of COPD stage II or higher was 4.4% (95%CI; 3.8%–5.1%). The prevalence of COPD increased with age and with cigarette smoking and was higher in those with a low educational level. A previous diagnosis of COPD was reported by only 27% of those with COPD. Diagnosed patients had more severe disease, higher cumulative tobacco consumption and more severely impaired HRQL compared with undiagnosed subjects. However, even patients with undiagnosed COPD stage I+ already showed impairment in HRQL and in some aspects of ADL compared with participants without COPD. <h3>Conclusions:</h3> The prevalence of COPD in individuals between 40 and 80 years of age in Spain is 10.2% and increases with age, tobacco consumption and lower educational levels. The rate of diagnosised COPD is very high and undiagnosed individuals with COPD already have a significant impairment in HRQL and ADL.
Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis
Authors: David E. Kaplan, Fusao Ikeda, Yun Li, Nobuhiro Nakamoto, Sutharsan Ganesan, Mary E. Valiga, Frederick A. Nunes, K. Rajender Reddy, Kyong-Mi Chang
Journal: Journal of Hepatology (2008)
Nano in Cancer: Linking Chemistry, Biology, and Clinical Applications <i>In Vivo</i>
Authors: Robin S Dothager, David Piwnica-Worms
Journal: Cancer Research (2011)

Abstract Development of nanoparticle agents for cancer therapeutics and diagnostics is steadily progressing and was the subject of the inaugural conference entitled, “Nano in Cancer,” held during January 12–15, 2011, in Miami, FL. The meeting program was developed by co-chairs David Piwnica-Worms (Washington University in St. Louis), Jan Schnitzer (Proteogenomics Research Institute for Systems Medicine, San Diego), and Karen Wooley (Texas A&amp;M University). Topics discussed for nanoparticle platforms under development included: nanotechnologies for cancer diagnostics and imaging, overcoming in vivo barriers, therapeutic nanoparticles and clinical prospects, and safety issues for nanotechnologies. Two important concepts emerged from this meeting. The first was the urgent need for uniform standards and protocols for nanoparticle characterization in vitro and in vivo, and the second was the continued need for discovery of definitive targets for tumor-directed nanoparticles across various cancers. Cancer Res; 71(17); 5611–5. ©2011 AACR.
Cortical Serotonin 5-HT <sub>2A</sub> Receptor Binding and Social Communication in Adults With Asperger’s Syndrome: An in Vivo SPECT Study
Authors: Declan G.M. Murphy, Eileen Daly, Nicole Schmitz, Fiona Toal, Keiran Murphy, Sarah Curran, Kjell Erlandsson, Jos Eersels, Robert Kerwin, Peter Ell, Michael Travis
Journal: American Journal of Psychiatry (2006)

Objective: The cause of autistic spectrum disorder (i.e., autism and Asperger's syndrome) is unknown. The serotonergic (5-HT) system may be especially implicated. However, cortical 5-HT 2A receptor density in adults with the disorder has not been examined, to the authors' knowledge. Method: The authors investigated cortical 5-HT 2A receptor binding in eight adults with Asperger's syndrome and in 10 healthy comparison subjects with single photon emission computed tomography and the selective 5-HT 2A receptor ligand 123I iodinated 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide ( 123 I-5-I-R91150). Results: People with Asperger's syndrome had a significant reduction in cortical 5-HT 2A receptor binding in the total, anterior, and posterior cingulate; bilaterally in the frontal and superior temporal lobes; and in the left parietal lobe. Also, reduced receptor binding was significantly related to abnormal social communication. Conclusions: The authors' findings suggest that adults with Asperger's syndrome have abnormalities in cortical 5-HT 2A receptor density and that this deficit may underlie some clinical symptoms.
Molecular and Biological Characterization of the Murine Leukotriene B4 Receptor Expressed on Eosinophils
Authors: Wei-Wei Huang, Eduardo A. Garcia-Zepeda, Alain Sauty, Hans C. Oettgen, Marc E. Rothenberg, Andrew D. Luster
Journal: The Journal of Experimental Medicine (1998)

The movement of leukocytes into tissues is regulated by the local production of chemical mediators collectively referred to as chemoattractants. Although chemoattractants constitute a diverse array of molecules, including proteins, peptides, and lipids, they all appear to signal leukocytes through a related family of seven transmembrane–spanning G protein–coupled receptors. The eosinophil is a potent proinflammatory cell that is attracted into tissues during allergic inflammation, parasitic infection, and certain malignancies. Since the molecular mechanisms controlling eosinophil recruitment are incompletely understood, we performed a degenerate polymerase chain reaction on cDNA isolated from murine eosinophils to identify novel chemoattractant receptors. We report the isolation of a cDNA that encodes a 351–amino acid glycoprotein that is 78% identical to a human gene that has been reported to be a purinoceptor (P2Y7) and a leukotriene B4 (LTB4) receptor (BLTR). Chinese hamster ovary (CHO) cells transfected with this cDNA specifically bound [3H]LTB4 with a dissociation constant of 0.6 ± 0.1 nM. Furthermore, LTB4 induced a dose-dependent intracellular calcium flux in transfected CHO cells. In contrast, [35S]dATP did not specifically bind to these transfectants. This mRNA was expressed at high levels in interleukin 5–exposed eosinophils, elicited peritoneal macrophages and neutrophils, and to a lesser extent interferon γ stimulated macrophages. Low levels of expression were detected in the lung, lymph node, and spleen of unchallenged mice. Western blot analysis detected the mBLTR protein in murine eosinophils and alveolar macrophages as well as human eosinophils. In addition, elevated levels of mBLTR mRNA were found in the lungs of mice in a murine model of allergic pulmonary inflammation in a time course consistent with the influx of eosinophils. Our findings indicate that this murine receptor is an LTB4 receptor that is highly expressed on activated leukocytes, including eosinophils, and may play an important role in mediating eosinophil recruitment into inflammatory foci.