tbuckley/cabot-search huggingface dataset:
The Contribution of Bone Marrow–Derived Cells to the Tumor Vasculature in Neuroblastoma Is Matrix Metalloproteinase-9 Dependent
Authors: Sonata Jodele, Christophe F. Chantrain, Laurence Blavier, Carolyn Lutzko, Gay M. Crooks, Hiroyuki Shimada, Lisa M. Coussens, Yves A. DeClerck
Journal: Cancer Research (2005)

Abstract The contribution of the tumor stroma to cancer progression has been increasingly recognized. We had previously shown that in human neuroblastoma tumors orthotopically implanted in immunodeficient mice, stromal-derived matrix metalloproteinase-9 (MMP-9) contributes to the formation of a mature vasculature by promoting pericyte recruitment along endothelial cells. Here we show that MMP-9 is predominantly expressed by bone marrow–derived CD45-positive leukocytes. Using a series of bone marrow transplantation experiments in MMP-9+/+ and MMP-9−/− mice xenotransplanted with human neuroblastoma tumors, we show that bone marrow–derived MMP-9 is critical for the recruitment of leukocytes from bone marrow into the tumor stroma and for the integration of bone marrow–derived endothelial cells into the tumor vasculature. Expression of MMP-9 by bone marrow–derived cells in the tumor stroma is also critical for the formation of a mature vasculature and coverage of endothelial cells with pericytes. Furthermore, in primary human neuroblastoma tumor specimens of unfavorable histology, we observed a higher level of tumor infiltration with MMP-9 expressing phagocytic cells and a higher degree of coverage of endothelial cells by pericytes when compared with tumor specimens with a favorable histology. Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow–derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression.
STUDIES ON THE ANTIGENIC COMPOSITION OF GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Walter A. Stewart, Rebecca C. Lancefield, Armine T. Wilson, Homer F. Swift
Journal: The Journal of Experimental Medicine (1944)

1. The occurrence of closely related T antigens in the series composed of types 15, 17, 19, 23, and 30 accounts for most of the cross reactions observed among these types. Similarly T antigens, unrelated to the first series but mutually related, occur in a second series comprising types 4, 24, 26, 28, 29, and 46. 2. Matt variants of each of the eleven types studied possess type-specific M antigens demonstrable either by precipitin or agglutinin reactions. 3. In seven of these types, strains have been encountered which do not possess the T antigen usually associated with the type in question. 4. Procedures are outlined in the appendix for preparing specific antisera for the classification of these types by the slide agglutination technique.
Clinical and molecular characterization of HER2 amplified-pancreatic cancer
Authors: Angela Chou, Nicola Waddell, Mark J Cowley, Anthony J Gill, David K Chang, Ann-Marie Patch, Katia Nones, Jianmin Wu, Mark Pinese, Amber L Johns, David K Miller, Karin S Kassahn, Adnan M Nagrial, Harpreet Wasan, David Goldstein, Christopher W Toon, Venessa Chin, Lorraine Chantrill, Jeremy Humphris, R Scott Mead, Ilse Rooman, Jaswinder S Samra, Marina Pajic, Elizabeth A Musgrove, John V Pearson, Adrienne L Morey, Sean M Grimmond, Andrew V Biankin
Journal: Genome Medicine (2013)

Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.
In vivo distribution, pharmacokinetics, and toxicity of aqueous synthesized cadmium-containing quantum dots
Authors: Yuanyuan Su, Fei Peng, Ziyun Jiang, Yiling Zhong, Yimei Lu, Xiangxu Jiang, Qing Huang, Chunhai Fan, Shuit-Tong Lee, Yao He
Journal: Biomaterials (2011)
Regulation of breathing in hyperthyroidism: relationship to hormonal and metabolic changes
Authors: JM Pino-Garcia, F Garcia-Rio, JJ Diez, MA Gomez-Mendieta, MA Racionero, S Diaz-Lobato, J Villamor
Journal: European Respiratory Journal (1998)

We sought to examine the breathing pattern, inspiratory drive and chemosensitivity of hyperthyroid patients and to explore the interactions between their thyroid hormones, basal metabolism and chemosensitivity. We studied 15 hyperthyroid patients and 15 sex- and age-matched controls. Thyroid hormone levels, arterial blood gas tensions, lung volumes, diffusing capacity for CO, maximal respiratory pressures and oxygen uptake measurements were performed. Breathing pattern and mouth occlusion pressure (P0.1), as well as ventilatory and P0.1 responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia, were also evaluated. Compared with the control subjects, the hyperthyroid patients showed significantly lower resting arterial CO2 tension, tidal volume and significantly higher mean inspiratory flow and P0.1. Ventilatory and P0.1 responses to CO2 and hypoxia were also greater in the hyperthyroid patients than in the control group. All these changes returned to normal after treatment. In the patients, significant relationships between tri-iodothyronine and P0.1, P0.1 response to hypoxia, and P0.1 response to hypercapnia were found. In contrast, in hyperthyroidism there was no relationship between oxygen uptake and P0.1 response to hypoxia. We conclude that hyperthyroid patients exhibit a significant relationship between their thyroid hormone levels and their increased inspiratory drive and chemosensitivity.
Human lung fibroblasts secrete nerve growth factor: effect of inflammatory cytokines and glucocorticoids
Authors: C. Olgart, N. Frossard
Journal: European Respiratory Journal (2001)

Nerve growth factor (NGF) has recently been suggested to contribute to inflammation and bronchial hyperresponsiveness in asthma. However, the cell types capable of NGF production in the human lung and airways, as well as the regulatory role of pro-inflammatory cytokines and of glucocorticoids on NGF secretion in pulmonary cells, have not been described. Human pulmonary fibroblasts were cultured in the presence or absence of either interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and/or glucocorticoids. NGF secretion was measured by enzyme-linked immunosorbent assay. The human pulmonary fibroblasts constitutively secreted NGF in vitro . The rate of NGF secretion was shown to be cell density-dependent, since higher NGF secretion was detected in preconfluent cells, i.e. ones with less established cell-to-cell contact (41.0±5.0 pg·10 −6 cells at 80% confluence), than cells in higher densities (8.2±3.4 pg·10 −6 cells at 100% confluence). Stimulation with the pro-inflammatory cytokines IL-1β (0.3–30 U·mL −1 ) or TNF-α (0.1–30 ng·mL −1 ) dose- and time-dependently (8–72 h) elevated the NGF secretion (effective concentration causing 50% of the maximum response (EC50)=2.9 U·mL −1 and 1.0 ng·mL −1 , respectively). Treatment with the glucocorticoid budesonide (10 −7 M) markedly reduced the constitutive secretion of NGF by 42%, and attenuated the cytokine-stimulated NGF secretion to the same level. In conclusion, human lung fibroblasts may serve as a source of nerve growth factor in the lung, positively regulated by the asthma-associated and pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α, and negatively regulated by the anti-inflammatory glucocorticoids.
Leukocyte Integrin Mac-1 Recruits Toll/Interleukin-1 Receptor Superfamily Signaling Intermediates to Modulate NF-κB Activity
Authors: Can Shi, Xiaobin Zhang, Zhiping Chen, Martyn K. Robinson, Daniel I. Simon
Journal: Circulation Research (2001)

The leukocyte integrin Mac-1 (αMβ2, CD11b/CD18) regulates important cell functions in inflammation, including adhesion, phagocytosis, and oxidative burst. Deficiency of Mac-1 reduces vessel wall inflammation and neointimal thickening after murine carotid artery injury. Although Mac-1 has been implicated in modulating AP-1 and NF-κB activity, the signal transduction pathways involved are undefined. cDNA array analysis of Mac-1–clustered compared with –nonclustered monocytic THP-1 cells showed increased expression of the signal transducer TRAF6 (TNF receptor–associated factor 6), leading us to consider the possibility that Mac-1 used a Toll/IL-1 receptor family–like signaling pathway. Mac-1–dependent activation of NF-κB was potentiated by wild-type, and attenuated by dominant negative, TRAF6- and TGF-β–activated kinase (TAK1) constructs. IRAK1 (IL-1 receptor associated kinase), a kinase immediately upstream of TRAF6, coimmunoprecipitated with Mac-1. Taken together, these observations indicate that Mac-1 recruits a Toll/IL-1 receptor family–like cascade to modulate NF-κB activity. This represents a new pathway for integrin-dependent modulation of gene expression.
Early Molecular Events in Antigen-Antibody Cell Activation
Authors: H Metzger
Journal: The Annual Review of Pharmacology and Toxicology (1979)

Immunoglobulins are multichained glycoproteins synthesized by all verte­ brate species, which serve as the fundamental recognition units in immune reactions. In such reactions they serve a dual role. One role is to serve as receptors, stimulation of which initiates the immune response to a particu­ lar antigen. This stimulation can result in both a proliferation of antigen­ specific lymphocytes and differentiation of lymphocytes into plasma cells that secrete antigen-specific immunoglobulins (antibodies). A second role of immunoglobulins is to serve as the effector substances which, upon interaction with the antigen, ultimately lead to disposal of the latter. Antibodies have no capacity to degrade or alter irreversibly the offending antigen. A variety of indirect mechanisms are utilized instead. For example, antibodies directed to surface antigens on a cell may destroy the cell by initiating a complex interaction involving the set of proteins collec­ tively called complement (1). Complement activation can directly damage cell plasma membranes leading to cytolysis. In other instances, particles coated with antibodies may become phagocytosed with subsequent degrada­ tion occurring in the phagocyte's lysozomes (2, 3). Still another mechanism (with which I deal in greater detail) involves adherence of antibodies to cells, exposure of which to the antigen initiates exocytosis of granules from the cells (4). The contents of these granules stimulate a variety of reactions that can be loosely grouped as inflammatory. These reactions are apparently directed to the removal of the antigen by nonspecific means.
Targeted delivery of docetaxel to the metastatic lymph nodes: A comparison study between nanoliposomes and activated carbon nanoparticles
Authors: Tiantian Ye, Wen Xu, Tianyu Shi, Rui Yang, Xinggang Yang, Shujun Wang, Weisan Pan
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes, which are used as carriers for delivering docetaxel (DTX) to the metastatic lymph nodes. In this study, we first prepared the DTX-loaded activated carbon nanoparticles (DTX-AC-NPs) by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon. We then prepared DTX-loaded nanoliposomes (DTX-LPs) by the proliposome method. The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro. The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites. The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies. DTX-AC-NPs significantly increased DTX-AUC(0–24) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo. This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.
Hepatitis C viremia in chronic liver disease: Relationship to interferon-α or corticosteroid treatment
Authors: Silvio Magrin, Antonio Craxi, Carmelo Fabiano, Rosa Giovanna Simonetti, Germana Fiorentino, Liliana Marino, Orazia Diquattro, Vito Di Marco, Oreste Loiacono, Riccardo Volpes, Piero Almasio, Mickey S. Urdea, Paul Neuwald, Ray Sanchez-Pescador, Jill Detmer, Judith C. Wilber, Luigi Pagliaro
Journal: Hepatology (1994)

We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody-positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p &lt; 0.001). Mean viremia level (× 10 3 genome equivalents/ml ± S.D.), as assessed with the branched-DNA test, was 5,700 ± 7,618 in the 48 patients with chronic hepatitis, 3,340 ± 3,633 in the 21 patients with cirrhosis and 1,768 ± 2,770 in the 31 patients with hepatocellular carcinoma (p &lt; 0.02). We also analyzed retrospectively the relationship between viremia and treatment. Fifty-five patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-α treatment. Mean viremia level was comparable among the 30 responders (5,644 ± 8,207) and the 25 nonresponders (5,519 ± 6,208) to interferon, but it was significantly lower (1,841 ± 1,864) in the 12 of 30 responders (11 chronic hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with prednisone. The mean viremia level significantly increased after 3 mo of treatment, even in face of ALT decrease. In conclusion, serum hepatitis C virus RNA is detectable in almost all patients with hepatitis C virus antibody-positive chronic liver disease, polymerase chain reaction being more sensitive than the branched-DNA test. Hepatitis C viremia is lowest in patients with advanced liver disease. A low pretreatment value of viremia could identify patients with chronic hepatitis who will derive long-term benefit from interferon. Corticosteroids generally increase viremia in hepatitis C virus antibody-positive, autoantibody-positive chronic hepatitis, independent of ALT response. (Hepatology 1994;19:273-279).
Air Pollution Exposure and Abnormal Glucose Tolerance during Pregnancy: The Project Viva Cohort
Authors: Abby F. Fleisch, Diane R. Gold, Sheryl L. Rifas-Shiman, Petros Koutrakis, Joel D. Schwartz, Itai Kloog, Steven Melly, Brent A. Coull, Antonella Zanobetti, Matthew W. Gillman, Emily Oken
Journal: Environmental Health Perspectives (2014)

Background: Exposure to fine particulate matter (PM with diameter ≤ 2.5 μm; PM2.5) has been linked to type 2 diabetes mellitus, but associations with hyperglycemia in pregnancy have not been well studied.Methods: We studied Boston, Massachusetts–area pregnant women without known diabetes. We identified impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) during pregnancy from clinical glucose tolerance tests at median 28.1 weeks gestation. We used residential addresses to estimate second-trimester PM2.5 and black carbon exposure via a central monitoring site and spatiotemporal models. We estimated residential traffic density and roadway proximity as surrogates for exposure to traffic-related air pollution. We performed multinomial logistic regression analyses adjusted for sociodemographic covariates, and used multiple imputation to account for missing data.Results: Of 2,093 women, 65 (3%) had IGT and 118 (6%) had GDM. Second-trimester spatiotemporal exposures ranged from 8.5 to 15.9 μg/m3 for PM2.5 and from 0.1 to 1.7 μg/m3 for black carbon. Traffic density was 0–30,860 vehicles/day × length of road (kilometers) within 100 m; 281 (13%) women lived ≤ 200 m from a major road. The prevalence of IGT was elevated in the highest (vs. lowest) quartile of exposure to spatiotemporal PM2.5 [odds ratio (OR) = 2.63; 95% CI: 1.15, 6.01] and traffic density (OR = 2.66; 95% CI: 1.24, 5.71). IGT also was positively associated with other exposure measures, although associations were not statistically significant. No pollutant exposures were positively associated with GDM.Conclusions: Greater exposure to PM2.5 and other traffic-related pollutants during pregnancy was associated with IGT but not GDM. Air pollution may contribute to abnormal glycemia in pregnancy.Citation: Fleisch AF, Gold DR, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, Coull BA, Zanobetti A, Gillman MW, Oken E. 2014. Air pollution exposure and abnormal glucose tolerance during pregnancy: the Project Viva Cohort. Environ Health Perspect 122:378–383; http://dx.doi.org/10.1289/ehp.1307065
Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 5-year results of the GO-RAISE study
Authors: Atul Deodhar, Jürgen Braun, Robert D Inman, Désirée van der Heijde, Yiying Zhou, Stephen Xu, Chenglong Han, Benjamin Hsu
Journal: Annals of the Rheumatic Diseases (2014)

Assess golimumab efficacy/safety through 5 years in patients with active ankylosing spondylitis (AS).356 patients with AS were randomly assigned to placebo, golimumab 50 mg or 100 mg every 4 weeks. At week 16, patients with inadequate response early escaped with blinded dose adjustments (placebo to 50 mg, 50 mg to 100 mg). At week 24, all patients receiving placebo crossed over to 50 mg. Blinded active therapy continued through week 104; from week 104 to week 252, the golimumab dose could be adjusted. Intent-to-treat and observed efficacy data were assessed by randomised treatment groups.At week 256, and with >4.5 years of golimumab, overall intent-to-treat Assessment in SpondyloArthritis international Society criteria for 20% improvement (ASAS20) and ASAS40 response rates were 66.0% (235/356) and 57.0% (203/356), respectively; Bath AS Disease Activity Index 50% improvement response was 55.9% (199/356). Observed response rates among the 255 (72%) patients who continued golimumab through week 252 were consistent, albeit somewhat higher. Among patients who increased golimumab from 50 to 100 mg, 60.6% (20/33) and 44.7% (17/38) achieved ASAS20/ASAS40 responses, respectively, following ≥2 consecutive doses of golimumab 100 mg. Golimumab safety through week 268 was similar to that through week 24 regardless of dose.Clinical improvements observed in patients treated with golimumab through week 24 were sustained through week 256 (5 years). Long-term golimumab safety is consistent with that of other established tumour-necrosis-factor-antagonists.ClinicalTrials.gov: NCT00265083.
A Study of Rubella Immunity and Resistance to Infection
Authors: William J. Davis
Journal: JAMA (1971)

During a rubella outbreak, the effect of exposure on 33 susceptible persons, 22 vaccinees, and 66 others with immunity from earlier rubella was studied. Groups were examined daily and specimens were collected for virologic testing. Infection occurred in 22 of the susceptible persons; all tested were viremic, excreted copious amounts of virus, and had clinical rubella. None of the previously vaccinated or naturally immune individuals developed rubella. Antibody boosts indicative of subclinical reinfection occurred in five vaccinees and one naturally immune child; these six were not demonstrably viremic, and only two vaccinees excreted virus. Antibody level appeared to influence resistance to reinfection. However, any detectable antibody protected against disease, prevented viremia, and blocked or modified pharyngeal virus replication. It was concluded that rubella exposure of vaccinees with antibodies was unlikely to constitute a significant clinical or epidemiologic risk.
Small intestinal plasma cells in coeliac disease.
Authors: B B Scott, A Goodall, P Stephenson, D Jenkins
Journal: Gut (1984)

Using a modified immunoperoxidase technique to achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue, IgA, IgM, IgE, and IgG plasma cells were studied in small bowel biopsies from 20 controls, 23 untreated coeliac patients, 19 treated coeliac patients, and seven patients with Crohn9s disease not involving duodenum or jejunum. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 2.5:1:1:1 respectively. In patients with untreated coeliac disease, counts of all types of plasma cell were significantly increased approximately two-fold compared with controls although for IgG cells there was considerable overlap. The ratio of the mean plasma cell counts in the untreated coeliac patients was 3.5:1.5:2:1. Counts fell significantly after treatment with a gluten-free diet. There was no significant difference between counts in the controls and the Crohn9s disease patients. The changes found in coeliac disease may simply be a non-specific response to mucosal damage. The increases in IgA and IgM plasma cells, however, suggest that the deposits of extracellular IgA and IgM observed in coeliac mucosa are locally produced, and the increase in IgE plasma cells raises the possibility that reaginic type hypersensitivity may be involved in coeliac disease.
Gefitinib and Pemetrexed As a First Line Treatment in Patients with Egfr Mutant Advanced Nsclc: a Phase Ii Study
Authors: N. Yoshimura, S. Mitsuoka, N. Yoshimoto, T. Nakai, T. Oka, K. Matsuura, T. Kimura, S. Kudoh, T. Kawaguchi, K. Hirata
Journal: Annals of Oncology (2014)