tbuckley/cabot-search huggingface dataset:
House dust mite induces direct airway inflammation in vivo: implications for future disease therapy?
Authors: J. De Alba, K. Raemdonck, A. Dekkak, M. Collins, S. Wong, A. T. Nials, R. G. Knowles, M. G. Belvisi, M. A. Birrell
Journal: European Respiratory Journal (2009)

House dust mite (HDM) is the major source of allergen in house dust and is strongly associated with the development of asthma. HDM can evoke a direct, nonallergic inflammatory reaction in vitro. We aimed to determine whether this apparent nonallergic, inflammatory response can be observed in a more complex in vivo setting. Vehicle, Alum or HDM (Dermatophagoides pteronyssinus 5 microg, i.p. with Alum) sensitised Brown-Norway rats were challenged intratracheally with vehicle (saline), HDM (Der p 10 microg) or heat-inactivated HDM on day 21. Lung function changes and the associated inflammatory response were evaluated. Tissue and bronchoalveolar lavage from Alum sensitised Der p challenged animals exhibited strong eosinophilia and neutrophilia associated with an early release of pro-inflammatory cytokines (interleukin-13 and 1beta, eotaxin and thymus and activation-regulated chemokine). This response was not attenuated by removal of HDM-associated protease activity. Interestingly, the vehicle sensitised group (no Alum) lacked this inflammatory response. HDM allergen evokes nonallergic airways inflammation with an inflammatory profile similar to that of the asthmatic airway. This response, independent of the protease activity of the HDM extract, appeared to be linked to prior administration of the adjuvant Alum and the subsequent increase in total immunoglobulin E. This finding could have important implications in the development of future asthma therapies.
TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase
Authors: Jie Fan, Randall S. Frey, Asrar B. Malik
Journal: Journal of Clinical Investigation (2003)

Interactions of polymorphonuclear neutrophils (PMNs) with endothelial cells may contribute to the activation of endothelial cell responses involved in innate immunity. We explored a novel function of PMN NADPH oxidase in the mechanism of Toll-like receptor-2 (TLR2) upregulation induced by LPS-TLR4 signaling in endothelial cells. We showed that LPS induced TLR2 up-regulation through TLR4- and MyD88-dependent signaling. In neutropenic mice, the LPS-induced NF-kB activation and TLR2 expression were significantly reduced, and both responses were restored upon repletion by PMN obtained from WT mice but not by PMNs from NADPH oxidase gp91phox–/– mice. These findings were recapitulated in mouse lung vascular endothelial cells cocultured with PMNs, indicating that the augmented NF-kB activation and the resultant TLR2 upregulation in endothelial cells were secondary to oxidant signaling generated by PMN NADPH oxidase. The functional relevance of NADPH oxidase in mediating TLR4-induced TLR2 expression in endothelial cells was evident by markedly elevated and stable ICAM-1 expression as well as augmented PMN migration in response to sequential challenge with LPS and peptidoglycan. Thus, PMN NADPH oxidase–derived oxidant signaling is an important determinant of the cross talk between TLR4 and TLR2 and the control of endothelial cell activation.
Fathers at Delivery
Authors: G. L. Davies
Journal: BMJ (1961)

<h3>Background</h3> Systemic sclerosis (SSc) is characterized by progressive diffuse microvascular damage and decreased blood perfusion (BP) at skin and internal organs (1). Laser speckled contrast analysis (LASCA) evaluate skin BP in different areas of body (2). Histological studies and fluorescein angiography demonstrated choroidal involvement in SSc, and recently optical coherence tomography (OCT) measurement showed significantly thinner choroid thickness (CT) in SSc patients (3–5). Iloprost, a prostacycline analogue, is effective in the treatment of microvascular manifestations in SSc (7). <h3>Objectives</h3> To study skin BP and ocular CT in patients with SSc, before and after iloprost treatment. <h3>Methods</h3> After informed consent was obtained, twelve SSc patients according to ACR/EULAR classification criteria (8) (mean age 58±13 years, mean disease duration 5±3 years) underwent ophthalmologic evaluation by OCT and BP evaluation by LASCA, before after 8 hours of continuous iloprost i.v. infusion (0.5 ng/kg/min). OCT images were recorded by 3D-2000 OCT (Topcon, Japan) using protocol “line” that averages 50 B-scans and generates a horizontal 6 mm line. CT area measurements were performed manually using image J software. BP was assessed by LASCA at the level of fingertips, periungueal, whole face, perioral and periorbital area, and the average BP calculated as perfusion units (PU)(1). Statistical analysis was performed by non parametric tests. <h3>Results</h3> Both before and after iloprost therapy (T0-T1), statistically significant positive correlations between BP and CT were found at periorbital (T0 r=0.55, p=0.022, and T1 r=0.91 p=0.0002), fingertips (T0 r=0.69, p=0.004, and T1 r=0.63, p=0.01), and perioral skin areas (T0 r=0,75, p=0.002, and T1 r=0,61, p=0.012). Further correlations were observed at periungueal (T0 r=0.54, p=0.02, and T1 r=0.50, p=0.04) and whole face (T0 r=0.49, p=0.04, and T1 r=0.47, p=0.05). BP was found significantly increased after iloprost therapy in all examined areas (p=0.002). Patients did not show any visual/ocular symptom during and after iloprost infusion. <h3>Conclusions</h3> LASCA and OCT seem concordant tools in assessing the functional microvascularization status in SSc patients. Since LASCA is a reliable tool to assess skin BP, its observed correlation with the CT and the effects of iloprost treatment, suggest that the OCT evaluation could be included in periodical instrumental evaluation of SSc progression and effects of microvascular targeted treatments. <h3>References</h3> Rosato E, et al Rheumatology 2009;36:2257–63. Ruaro B, et al Ann Rheum Dis 2014;73:1181–5. Farkas TG, et al Am J Ophthalmol 1972;74:875–886. Serup L, et al Ophthalmic Res 1987;19:303–308. Ingegnoli F, et al Microvasc Res 2015;97:31–36. Yamashita T, et al Invest Ophthalmol Vis Sci 2012;53:1102–1107. Scorza R, et al Clin Exp Rheumatol 2001; 19:503–8. Van den Hoogen F, et al. Ann Rheum Dis. 2013;72:1747–55. <h3>Disclosure of Interest</h3> None declared
Steroid Receptor Regulation of Epidermal Growth Factor Signaling through Src in Breast and Prostate Cancer Cells: Steroid Antagonist Action
Authors: Antimo Migliaccio, Marina Di Domenico, Gabriella Castoria, Merlin Nanayakkara, Maria Lombardi, Antonietta de Falco, Antonio Bilancio, Lilian Varricchio, Alessandra Ciociola, Ferdinando Auricchio
Journal: Cancer Research (2005)

Abstract Under conditions of short-term hormone deprivation, epidermal growth factor (EGF) induces DNA synthesis, cytoskeletal changes, and Src activation in MCF-7 and LNCaP cells. These effects are drastically inhibited by pure estradiol or androgen antagonists, implicating a role of the steroid receptors in these findings. Interestingly, EGF triggers rapid association of Src with androgen receptor (AR) and estradiol receptor α (ERα) in MCF-7 cells or ERβ in LNCaP cells. Here, we show that, through EGF receptor (EGFR) and erb-B2, EGF induces tyrosine phosphorylation of ER preassociated with AR, thereby triggering the assembly of ER/AR with Src and EGFR. Remarkably, experiments in Cos cells show that this complex stimulates EGF-triggered EGFR tyrosine phosphorylation. In turn, estradiol and androgen antagonists, through the Src-associated receptors, prevent Src activation by EGF and heavily reduce EGFR tyrosine phosphorylation and the subsequent multiple effects, including DNA synthesis and cytoskeletal changes in MCF-7 cells. In addition, knockdown of ERα or AR gene by small interfering RNA (siRNA) almost abolishes EGFR tyrosine phosphorylation and DNA synthesis in EGF-treated MCF-7 cells. The present findings reveal that steroid receptors have a key role in EGF signaling. EGFR tyrosine phosphorylation, depending on Src, is a part of this mechanism. Understanding of EGF-triggered growth and invasiveness of mammary and prostate cancer cells expressing steroid receptors is enhanced by this report, which reveals novel aspects of steroid receptor action.
Soy-Derived Isoflavones Inhibit the Growth of Canine Lymphoid Cell Lines
Authors: Vahbiz Jamadar-Shroff, Mark G. Papich, Steven E. Suter
Journal: Clinical Cancer Research (2009)

Abstract Purpose: This study aimed to evaluate the in vitro effects of genistein, both pure genistein and a commercially available form of genistein called Genistein Combined Polysacharride (GCP), against two canine B-cell lymphoid cell lines and determine the oral bioavailability of GCP when fed to normal dogs. Experimental Design: The in vitro effect of genistein and GCP was evaluated using cell proliferation and apoptotic assays. The IC50 of both compounds was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay and propidium idodide staining. Apoptosis was evaluated using Annexin V staining, caspase 3 and 9 staining, and DNA laddering. Cell cycle analysis and Bcl-2/Bax ratios were also examined. An initial dose escalating pharmacokinetic study was used to determine if therapeutic serum levels of genistein could be reached with oral dosing of GCP in normal dogs. Results: The 72-hour in vitro IC50 of genistein and GCP against the GL-1 and 17-71 cells were both 10 μg/mL and 20 μg/mL, respectively. GCP led to cell death in both cell lines via apoptosis and treated cells exhibited increased Bax:Bcl-2 ratios. The serum concentrations of genistein in normal dogs given increasing oral doses of GCP did not reach the 72-hour in vitro IC50 in a dose escalation study. Conclusions: The results of these studies support the notion that canine high-grade B-cell lymphoma may represent a relevant large animal model of human non-Hodgkin's lymphoma to investigate the utility of GCP in chemopreventive and/or treatment strategies that may serve as a prelude to human clinical lymphoma trials.
Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250.
Authors: E Oosterwijk, N H Bander, C R Divgi, S Welt, J C Wakka, R D Finn, E A Carswell, S M Larson, S O Warnaar, G J Fleuren
Journal: Journal of Clinical Oncology (1993)

PURPOSE To define the imaging and biodistribution characteristics of iodine 131-labeled monoclonal antibody (mAb) G250 (131I-mAbG250), which recognizes a cell-surface antigen expressed by human renal cell carcinoma (RCC). PATIENTS AND METHODS G250 is a cell-surface antigen recognized by mAbG250 expressed by RCC but not detected in normal kidney. Clear-cell RCC, the most frequent form of RCC, shows homogeneous expression of G250, whereas non-clear-cell RCC and cancers derived from other organs generally do not express G250. Expression in normal tissues is highly restricted and limited to large bile ducts and gastric epithelium. 131I-mAbG250 was administered intravenously (IV) to 16 patients with RCC 7 to 8 days before surgery at five dose levels, with at least three patients entered at each dose level. RESULTS Clear tumor images were observed in 12 patients with G250-positive tumors and in one of three patients with G250-negative tumors. Imaged lesions in the peritoneal cavity were confirmed at surgery. The smallest lesion visualized was 8 mm in diameter. The specificity of 131I-mAbG250 localization to tumor tissue was established by radioactivity measurements, autoradiography, and immunohistochemistry of biopsied tissues, and technetium 99-human serum albumin blood-flow studies. The fraction of the injected 131I-mAbG250 dose per gram tumor (%ID/g tumor) localized in G250-positive tumors showed a broad range, but reached levels as high as 0.02% to 0.12%. CONCLUSION 131I-mAbG250 localized specifically to G250 antigen-positive RCC and seems to have considerable potential as an imaging agent in RCC patients. 131I-mAbG250 uptake in the tumors, relative as well as absolute, are among the highest reported for tumor biopsies obtained 8 days after IV mAb administration. Based on the specific localization and high accumulation, mAb G250 may have therapeutic potential.
COLLAGEN METABOLISM IN THE NORMAL AND LATHYRITIC CHICK
Authors: Marvin L. Tanzer, Jerome Gross
Journal: The Journal of Experimental Medicine (1964)

1. Radioisotope incorporation studies of normal and lathyritic chick embryo bone collagen do not demonstrate any interference by lathyrism with collagen synthesis or fibril formation. 2. The results indicate that a portion of the extractable collagen from lathyritic chick embryo bone represents newly synthesized protein. Evidence from a double labeling experiment and from analysis of isotope flow between the extractable and non-extractable pools suggests the extractable lathyritic collagen is heterogeneous. We propose that the lathyritic process affects collagen in all states of aggregation, probably in varying degree. 3. Puromycin, administered intravenously, reduces the amount of extractable collagen in both normal and lathyritic chick embryo bone, and diminishes the incorporation of labeled proline into collagen. 4. Marked fluctuations in incorporation of labeled amino acids into chick embryo bone collagen suggests the occurrence of wide fluctuations in metabolism of this protein.
Analyzing the Results of the Treating to New Targets Study
Authors: Robert A. Alter
Journal: Annals of Internal Medicine (2008)

Letters19 February 2008Analyzing the Results of the Treating to New Targets StudyRobert A. Alter, MDRobert A. Alter, MDFrom Advocate Health Centers, Chicago, IL 60616.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-4-200802190-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The title of the article by Wenger and colleagues (1) is misleading. The design of the TNT (Treating to New Targets) study notes a maximum age of 75 years. Therefore, a more accurate title would replace “in patients 65 years of age or older” with “in patients 65 to 75 years of age.” All of the figures and tables should include similar language. Articles, textbooks, and advertisements often include such figures and tables without a description of the study population. When the study population age is clearly defined, authors should avoid imprecise terms that inappropriately generalize the ...Reference1. Wenger NK, Lewis SJ, Herrington DM, Bittner V, Welty FK; for the Treating to New Targets Study Steering Committee and Investigators. Outcomes of using high- or low-dose atorvastatin in patients 65 years of age or older with stable coronary heart disease. Ann Intern Med. 2007;147:1-9. [PMID: 17606955] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Advocate Health Centers, Chicago, IL 60616.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOutcomes of Using High- or Low-Dose Atorvastatin in Patients 65 Years of Age or Older with Stable Coronary Heart Disease Nanette K. Wenger , Sandra J. Lewis , David M. Herrington , Vera Bittner , Francine K. Welty , and Analyzing the Results of the Treating to New Targets Study Luca Mascitelli and Eddie Vos Analyzing the Results of the Treating to New Targets Study Mark R. Goldstein Analyzing the Results of the Treating to New Targets Study Vera Bittner , David Herrington , and Nanette Wenger Metrics 19 February 2008Volume 148, Issue 4Page: 321KeywordsConflicts of interest ePublished: 19 February 2008 Issue Published: 19 February 2008 CopyrightCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Bactericidal/Permeability-Increasing Protein (rBPI <sub>21</sub> ) and Fluoroquinolone Mitigate Radiation-Induced Bone Marrow Aplasia and Death
Authors: Eva C. Guinan, Christine M. Barbon, Leslie A. Kalish, Kalindi Parmar, Jeff Kutok, Christy J. Mancuso, Liat Stoler-Barak, Eugénie E. Suter, Janice D. Russell, Christine D. Palmer, Leighanne C. Gallington, Annie Voskertchian, Jo-Anne Vergilio, Geoffrey Cole, Kaya Zhu, Alan D’Andrea, Robert Soiffer, Jerrold P. Weiss, Ofer Levy
Journal: Science Translational Medicine (2011)

Even when given 24 hours after lethal radiation, a fragment of an endotoxin-neutralizing protein plus a fluoroquinolone antibiotic improves survival and hematopoietic recovery in mice.
The effect of aminophylline on respiratory and limb muscle contractility in man
Authors: C Brophy, A Mier, J Moxham, M Green
Journal: European Respiratory Journal (1989)

The effect of oral aminophylline on respiratory muscle and quadriceps femoris strength was compared with placebo in five normal subjects. A double-blind randomized cross-over protocol, spanning 2-3 wks, was followed. Aminophylline was taken before both placebo and active drug periods to establish correct dosage, to allow tolerance to side-effects to develop, and to keep the two limbs of the study identical and double-blind. Maximal static inspiratory and expiratory mouth pressures at residual volume and total lung capacity, respectively, maximal sniff transdiaphragmatic pressure, maximal voluntary quadriceps femoris contraction force and theophylline levels were measured during placebo and active drug periods. For the group, there were no significant differences between respiratory or quadriceps muscle strength on aminophylline and on placebo although there was a tendency for greater values on aminophylline. Mean theophylline level was 14.6 mg.l-1 (range 8.4-25.0 mg.l-1). We conclude that aminophylline produces no enhancement of skeletal muscle strength, at therapeutic dosage in normal subjects.
Does Diabetes Care Compete With the Provision of Women’s Preventive Care Services?
Authors: Bahman P. Tabaei, William H. Herman, Annissa F. Jabarin, Catherine Kim
Journal: Diabetes Care (2005)

OBJECTIVE—Care for chronic diseases may compete with preventive health care. To test this hypothesis, we examined the association between diabetes-related processes of care and preventive care in women. RESEARCH DESIGN AND METHODS—Using data from a prospective cohort study of diabetes care in managed care settings, we reviewed the care 540 diabetic women received from 355 primary care providers within 14 provider groups from one health plan. Of the 540 women, 278 were eligible to receive mammograms and 314 were eligible to receive Pap smears. Mammography performance was measured as at least one mammogram over a 2-year period and Pap performance was measured as at least one Pap smear over a 3-year period. To assess the association between diabetes-related processes of care and preventive services, we used hierarchical logistic regression models, accounted for clustering within provider groups, and adjusted for patient age, race, income and education level, diabetes treatment and duration, and health status, as well as physician age, sex, years of practice, and specialty. Diabetes-related processes of care were defined as dilated retinal examinations, urine microalbumin/protein testing, foot examinations, lipid and HbA1c testing, recommendations to take aspirin, and influenza vaccinations received over a 1-year period. RESULTS—In this cohort, 73% of eligible women received mammograms and 56% received Pap smears. After adjustment of models, better diabetes-related processes of care, better health status, and non-Medicaid insurance were associated with mammography performance. Better diabetes-related processes of care, younger patient age, and any visit to a gynecologist were associated with Pap performance. CONCLUSIONS—Better processes of diabetes care were associated with better women’s preventive health care. Diabetes management did not compete with sex-specific screening.
Conditional Survival after Hepatic Resection for Hepatocellular Carcinoma in Cirrhotic Patients
Authors: Alessandro Cucchetti, Fabio Piscaglia, Matteo Cescon, Giorgio Ercolani, Eleonora Terzi, Luigi Bolondi, Matteo Zanello, Antonio D. Pinna
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Survival estimates are commonly reported as actuarial survival after the first observation, but future survival probabilities can change over time. Conditional survival is a measure of prognosis for patients who have sometimes already survived several years since diagnosis; however, data on conditional survival for cirrhotic patients, resected for hepatocellular carcinoma (HCC), are lacking. Experimental Design: Clinical data from 300 consecutive cirrhotic patients who underwent HCC resection were reviewed and the actuarial survival estimated. The 5-year conditional survival was calculated as CS = S(x + 5)/S(x) and represents the probability of surviving an additional 5 years, given that the patient has already survived x years. Results: The 3-, 5-, and 10-year survival rates were, respectively, 69.0%, 57.7%, and 25.3% and were lower in cases of portal hypertension, Model for End-stage Liver Disease (MELD) score ≥9, United Network for Organ-Sharing T3 tumor, GIII–GIV tumors, and microscopic vascular invasion. However, the 5-year conditional survival calculation showed that patients resected for more advanced (T3) tumors or with adverse histologic features will experience the same survival probabilities as patients with less advanced tumors or favorable histology from the third year after surgery onward, as they had probably escaped recurrence from intrahepatic metastases. Patients who underwent repeated hepatectomy for recurrence presented higher conditional survival. Conclusions: Conditional survival showed that the impact of different variables influencing survival is not linear over time after hepatic resection. Information derived from conditional survival can be used to better manage patients with HCCs, including the potential future setting of adjuvant therapies and the choice of listing, or not, for transplantation resected patients not recurring within 2 years. Clin Cancer Res; 18(16); 4397–405. ©2012 AACR.
Actin Polymerization and Its Relationship to Adenosine Triphosphatase Activity
Authors: VEERARAGHAVAN K. MURTHY, LAMAR E. CREVASSE, JOSEPH C. SHIPP
Journal: Circulation Research (1968)

F-actin was prepared from pig heart myofibrils without the use of organic solvents. G-actin, prepared from F-actin by sonication, had adenosine triphosphatase activity. Dephosphorylation of added ATP by G-actin had a broad pH optimum between pH 7.5 and pH 9.0, specifically required Mg 2+ , and was activated by EGTA. G-actin prepared from skeletal muscle of rabbits by similar methods also showed ATPase activity. Cardiac G-actin and G-actin from skeletal muscle had equimolar nucleotide bound to them. Polymerization of cardiac G-actin was greatest at a pH of about 6.5 and declined above pH 6.8. KCl was necessary for polymerization, and EGTA inhibited the conversion to F-actin. By selectively acetylating G-actin, using acetic anhydride, a preparation of G-actin was obtained that did not have adenosine triphosphatase activity but did polymerize under optimal conditions. It is concluded that dephosphorylation of ATP and the polymerization process in cardiac G-actin are two different reactions occurring at different sites on the actin molecule.