tbuckley/cabot-search huggingface dataset:
Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: enhancement by the soluble products of encephalitogenic T cells.
Authors: J D MacMicking, D O Willenborg, M J Weidemann, K A Rockett, W B Cowden
Journal: The Journal of Experimental Medicine (1992)

Perivascular lesions within the central nervous system (CNS) of rats with hyperacute experimental autoimmune encephalomyelitis (HEAE) contained large numbers of peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMN), cells enzymatically capable of producing reactive nitrogen and oxygen intermediates (RNI and ROI), which, in excess, are mediators of tissue damage. PBMC and PMN isolated from the CNS and periphery of HEAE-affected rats secreted significantly (p less than 0.01-0.0001) elevated levels of ROI and RNI compared with that of similar cell populations from pertussis- and saline-treated control animals. Coincubation of systemically derived PBMC and PMN with antigen-stimulated myelin basic protein-specific T cell lines led to further increases in ROI and RNI output of between 15.3 and 83.1%, an effect that could be largely attributed to heat-labile, soluble products released by these T cell lines. Our studies suggest a putative neuropathological role for ROI and RNI in HEAE, which may be mediated via cytokines emanating from autoreactive T lymphocytes.
Pleuroparenchymal fibroelastosis from a consecutive database: a rare disease entity?
Authors: Takeshi Nakatani, Toru Arai, Masanori Kitaichi, Masanori Akira, Kazunobu Tachibana, Chikatoshi Sugimoto, Aya Hirooka, Taisuke Tsuji, Shojiro Minomo, Seiji Hayashi, Yoshikazu Inoue
Journal: European Respiratory Journal (2015)

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterised by predominantly upper lobe involvement with pleural fibrosis and subjacent parenchymal fibroelastosis [1, 2]. Idiopathic PPFE (IPPFE), which was included in the rare idiopathic interstitial pneumonias (IIPs) in the update of the international multidisciplinary classification of IIPs published in 2013 [3], was first described in the Japanese literature by Amitani et al. in 1992 [4]. PPFE has been reported to be associated with drugs, chronic hypersensitivity pneumonia, collagen vascular diseases, infections, and bone marrow transplantations [5–8]. However, the frequency of PPFE occurrence has been uncertain. We hypothesised that PPFE was not a rare disease entity and conducted this study. Informed consent was obtained from all patients, and the Institutional Review Board of the National Hospital Organization Kinki-Chuo Chest Medical Center (KCCMC) (Sakai City, Japan) approved this study. Idiopathic pleuroparenchymal fibroelastosis is an acceptable entity among IIPs and not as rare as previously reported <http://ow.ly/I5NEz>
Body position affects performance in untrained cyclists
Authors: M C Ashe, G C Scroop, P I Frisken, C A Amery, M A Wilkins, K M Khan
Journal: British Journal of Sports Medicine (2003)

To compare cardiovascular and ventilatory variables in upright versus aero cycle ergometry at submaximal and maximal exercise intensities in untrained cyclists.Ten physically active men (mean (SD) age 19.1 (1.10) years) who were unfamiliar with aerobars underwent maximal exercise testing and steady state cycling at 50, 100, and 150 W.Participants had significantly greater maxima for oxygen uptake (VO2), ventilation, heart rate, and workload maximum in the upright position. During steady state cycling at the three workloads, VO2 (ml/kg/min) and gross mechanical efficiency were significantly greater in the upright position.In untrained subjects performing with maximal effort, the upright position permits greater VO2, ventilation, heart rate, and workload maxima. Further, in the steady state, exercise cycling may be less costly in the upright position. For this reason, untrained cyclists need to weigh body position effects against the well known aerodynamic advantages of the aero position.
IVF/ICSI twin pregnancies: risks and prevention
Authors: Anja Pinborg
Journal: Human Reproduction Update (2005)

Since the 1970s, the national twin birth rates have been increasing worldwide. Apart from the increasing childbearing age, the main cause is the use of assisted reproductive technologies (ART). To explore the overall consequences of dual embryo transfer (DET), the literature has been reviewed systematically regarding short- and long-term outcomes of IVF/ICSI twin pregnancies i.e. pregnancy complications, maternal risks, obstetric outcome and long-term morbidity including neurological sequelae, cognitive development and family implications. Another consequence of DET is vanishing twins, which seems to be a possible cause of adverse outcome in IVF singletons. The sparse literature on vanishing twins in IVF pregnancies and the influence on the surviving co-twin were also addressed. Finally, to determine the effects of implementing elective single embryo transfer (eSET), trials concerning eSET versus DET were analysed. In the light of the steadily increasing twin birth rates and the findings in this overview, where IVF/ICSI twins carry adverse outcome, it should be emphasized that the major obstacle in IVF remains the high twin birth rate. Furthermore vanishing twins account for another hazard of DET. These problems can be resolved by implementing eSET, diminishing the twin birth rate without affecting the overall goal of achieving a healthy infant.
Overexpression of 5-Lipoxygenase in Rat and Human Esophageal Adenocarcinoma and Inhibitory Effects of Zileuton and Celecoxib on Carcinogenesis
Authors: Xiaoxin Chen, Su Wang, Nan Wu, Sandeep Sood, Peng Wang, Zhe Jin, David G. Beer, Thomas J. Giordano, Yong Lin, Wei-chung J. Shih, Ronald A. Lubet, Chung S. Yang
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Aberrant arachidonic acid (AA) metabolism, especially through the cyclooxygenase (Cox) and 5-lipoxygenase (5-Lox) pathways, has been suggested to play an important role in the development of esophageal adenocarcinoma (EAC). The purpose of this study was to investigate the expression of 5-Lox in EAC of a rat model and in human samples as well as the chemopreventive effects of zileuton (a specific 5-Lox inhibitor) and celecoxib (a specific Cox2 inhibitor) in the rat EAC model. Experimental Design: 5-Lox expression in EAC of a rat esophagogastroduodenal anastomosis model and of humans was examined with immunohistochemistry. A chemoprevention study was designed to test whether zileuton and celecoxib could suppress aberrant AA metabolism and esophageal adenocarcinogenesis. Results: With immunohistochemistry, we found that 5-Lox was overexpressed during esophageal adenocarcinogenesis in our rat model and in humans. In the chemoprevention study, EAC incidence was reduced in a dose-dependent manner from 68.8% (11 of 16) to 44.4% (8 of 18; P &amp;gt; 0.05) and 31.3% (5 of 16; P &amp;lt; 0.05) by 500 and 1,000 ppm zileuton, respectively, and to 33.3% (7 of 21; P &amp;lt; 0.05) and 20% (3 of 15; P &amp;lt; 0.05) by 500 and 1,000 ppm celecoxib, respectively. With isobolographic analysis, zileuton and celecoxib, both at a dose of 500 ppm, had an additive effect by reducing the tumor incidence to 16.7% (3 of 18, P &amp;lt; 0.01). Leukotriene B4 and prostaglandin E2 levels in the esophageal tissues were also significantly reduced by zileuton and celecoxib. Conclusions: This study clearly demonstrated that 5-Lox and Cox2 play important roles in the development of EAC. Both zileuton and celecoxib had inhibitory effects on esophageal adenocarcinogenesis through inhibition on their respective enzymes of AA metabolism.
Long-Term Effects of Hypertension on the Rat Aortic Wall and Their Relation to Concurrent Aging Changes: MORPHOLOGICAL AND CHEMICAL STUDIES
Authors: HARVEY WOLINSKY
Journal: Circulation Research (1972)

The effects of long-term (16 months) hypertension on the thoracic aorta of male rats were compared to previously reported short-term (2.5 months) changes and to concurrent aging changes. Hypertension was produced by clipping a renal artery. Although short-term hypertension was characterized by a disproportionate increase in noncollagenous alkali-soluble proteins, which have been attributed primarily to vascular smooth muscle, with long-term hypertension there was no further increase in these proteins but instead there were striking increases in mural accumulations of elastin and collagen. Chronically elevated wall tension in hypertensive vessels was associated with a progressive increase in wall thickness which resulted in a value for wall stress no different from that of control vessels. Concurrent aging changes were qualitatively similar to, but much less pronounced than, those seen with hypertension and were attributed to an increase in wall tension in controls resulting from a combination of significant increases in diameter and systolic blood pressure with age. This study of the interaction of vessel structure and function has revealed common features of what appears to be a diverse group of vascular alterations.
P3-14-09: A Phase II Preoperative Study of Dasatinib, a Multi-Targeted Tyrosine Kinase Inhibitor, in Locally Advanced “Triple-Negative” Breast Cancer Patients.
Authors: MF Rimawi, AA Rodriguez, WT Yang, AM Gonzalez-Angulo, JR Nangia, T Wang, C Speers, G Mills, SG Hilsenbeck, PH Brown, JC Chang
Journal: Cancer Research (2011)

Abstract Background: We previously reported that kinases (Src, Yes-1, cKIT, Abl, and EPH4) were druggable in triple negative breast cancer (TNBC). In this clinical trial, we sought to translate these findings by treating TNBC patients with dasatinib, a multi-targeted kinase inhibitor against these targets. Methods: Women with stage II-III TNBC were eligible. Patients received dasatinib at 100 mg daily for 3 to 4 weeks before standard-of-care definitive surgery and chemotherapy. Biopsies were performed at baseline, week 1, and at the time of surgery. A cohort of patients had positron emission mammography (PEM; baseline and at 2–3 weeks of dasatinib therapy). This study was designed to detect an increase in clinical response rate from 10% to 25%, using a Simon optimal two stage design, with one-sided alpha=5% and power=80%. At least 3 responses out of 22 patients were needed to proceed to the second stage. Results: 22 patients were enrolled (Table 1). Median tumor size was 7.0 cm (range 2.4-25 cm). Adverse events were modest, mainly grade 1–2 (headache: 45%, abnormal LFTs: 55%, GI: 23%, fatigue: 18%). One patient had a myocardial infarction 24 hours after starting dasatinib. Out of 22 patients, 2 (9%) had a clinical partial response after 3–4 weeks of therapy, 15 had stable disease (68%), while 5 had progressive disease (23%). Of the 8 patients who received paired PEM imaging, metabolic responses were observed in 2 patients (25%). Conclusion: A short course of dasatinib led to clinical responses in 2 out of 22 patients with TNBC, and the study did not proceed to second stage. Since TNBC is a heterogeneous disease, biomarker studies including sequencing of candidate genes like B-RAF for inactivating mutations might enable selection of those TNBC patients who could benefit from dasatinib. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-09.
An Acidic Peptide Sequence of Nucleolin-Related Protein Can Mediate the Attachment of Calcium Oxalate to Renal Tubule Cells
Authors: Elena A. Sorokina, Jeffrey A. Wesson, Jack G. Kleinman
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Crystals that form in tubular fluid must be retained in the kidney to become stones. Nucleolin-related protein (NRP) is found on the surface of inner medullary collecting duct (IMCD) cells in culture (cIMCD) and selectively adsorbs to calcium oxalate (CaOx). We proposed that NRP mediates attachment to the renal tubular epithelium of Ca stone crystals through an electrostatic interaction with a highly acidic region (acidic fragment [AF]) similar to those of other proteins that have been reported to affect urinary crystal formation. The current studies demonstrate that nucleolin is expressed on both apical and basolateral cell surfaces of cIMCD, reaching a peak in the late stages of mitosis and gradually declining to undetectable levels with maturation of the polarized epithelium. Scraping areas of mature monolayers stimulated the cells surrounding the defects to migrate and proliferate so as to repair them, and these areas demonstrate surface NRP expression and enhanced attachment of CaOx monohydrate crystals. Surface expression of the NRP AF was produced by cloning the NRP AF into a display vector. Transfected cIMCD demonstrating copious surface expression of AF enhanced CaOx attachment 6.7-fold compared with control cIMCD, whereas cells transfected with a vector without the AF did not differ from control. AF was also cloned into a replication-deficient adenovirus and expressed in 293 cells, resulting in AF secretion into the nutrient medium. This medium inhibited CaOx attachment to cIMCD, compared with conditioned medium from cells infected with wild-type virus. These results demonstrate that surface-bound AF can mediate CaOx attachment and that secreted AF can inhibit attachment. These results support the notion that surface-associated NRP could mediate attachment of CaOx to the renal tubule epithelium, thereby causing retention of crystals that might eventually become kidney stones.
Genistein Inhibits p38 Map Kinase Activation, Matrix Metalloproteinase Type 2, and Cell Invasion in Human Prostate Epithelial Cells
Authors: Xiaoke Huang, Shan Chen, Li Xu, Yueqin Liu, Dilip K. Deb, Leonidas C. Platanias, Raymond C. Bergan
Journal: Cancer Research (2005)

Abstract Epidemiologic studies associate consumption of genistein, in the form of dietary soy, with lower rates of metastatic prostate cancer. We have previously shown that genistein inhibits prostate cancer cell detachment in vitro, that it is well tolerated in an older cohort of men with prostate cancer, and that it alters cell signaling in that same cohort. We have also shown that p38 mitogen-activated protein kinase (MAPK) is necessary for transforming growth factor β (TGF-β)–mediated increases in prostate cancer adhesion. Although cell invasion is closely linked to metastatic behavior, little is known about how this process is regulated in prostate cancer or what effect, if any, genistein has on associated processes. We now show that genistein inhibits matrix metalloproteinase type 2 (MMP-2) activity in six of seven prostate cell lines tested, blocks MMP-2 induction by TGF-β, and inhibits cell invasion. Efficacy was seen at low nanomolar concentrations, corresponding to blood concentrations of free genistein attained after dietary consumption. Inhibition of p38 MAPK by either SB203580 or dominant-negative construct blocked induction of MMP-2 and cell invasion by TGF-β. Genistein exerted similar effects and was found to block activation of p38 MAPK by TGF-β. This study shows that p38 MAPK is necessary for TGF-β–mediated induction of MMP-2 and cell invasion in prostate cancer and that genistein blocks activation of p38 MAPK, thereby inhibiting processes closely linked to metastasis, and does so at concentrations associated with dietary consumption. Any potential causal link to epidemiologic findings will require further investigation.
PPAR- agonists as therapy for diseases involving airway neutrophilia
Authors: M.A. Birrell, H.J. Patel, K. McCluskie, S. Wong, T. Leonard, M.H. Yacoub, M.G. Belvisi
Journal: European Respiratory Journal (2004)

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear hormone receptors belonging to the steroid receptor superfamily. Previously, the present authors have shown that PPAR‐γ agonists inhibit the release of inflammatory cell survival factors and induce apoptosis <i>in vitro</i>. The aim of this study was to determine the effect of two structurally different PPAR agonists in an <i>in vivo</i> model of lipopolysaccharide (LPS)-induced airway inflammation. Mice were treated with PPAR agonists, rosiglitazone or SB 219994, prior to exposure to aerosolised LPS, and the extent of airway inflammation was assessed 3 h later. In these experiments, the PPAR ligands inhibited LPS-induced airway neutrophilia and associated chemoattractants/survival factors (keratinocyte-derived chemokine and granulocyte-colony stimulating factor) in the mouse lung. The present authors postulate that if a peroxisome proliferator-activated receptor agonist has the same effect in man, and neutrophils are important in the progression of respiratory diseases, such as chronic obstructive pulmonary disease, then this class of compounds could be a potential therapy. Furthermore, several peroxisome proliferator-activated receptor‐γ agonists have been shown to be clinically effective for the treatment of type II diabetes, suggesting that any benefit of peroxisome proliferator-activated receptor‐γ ligands in the progression of respiratory diseases, which may involve airway neutrophilia, could be explored relatively quickly.
Effect of Interleukin-8 Gene Silencing With Liposome-Encapsulated Small Interfering RNA on Ovarian Cancer Cell Growth
Authors: William M. Merritt, Yvonne G. Lin, Whitney A. Spannuth, Mavis S. Fletcher, Aparna A. Kamat, Liz Y. Han, Charles N. Landen, Nicholas Jennings, Koen De Geest, Robert R. Langley, Gabriel Villares, Angela Sanguino, Susan K. Lutgendorf, Gabriel Lopez-Berestein, Menashe M. Bar-Eli, Anil K. Sood
Journal: JNCI Journal of the National Cancer Institute (2008)

Interleukin-8 (IL-8) is a proangiogenic cytokine that is overexpressed in many human cancers. We investigated the clinical and biologic significance of IL-8 in ovarian carcinoma using human samples and orthotopic mouse models.Tumor expression of IL-8 was assessed by immunohistochemistry among ovarian cancer patients (n = 102) with available clinical and survival data. We examined the effect of IL-8 gene silencing with small interfering RNAs incorporated into neutral liposomes (siRNA-DOPCs), alone and in combination with docetaxel, on in vivo tumor growth, angiogenesis (microvessel density), and tumor cell proliferation in mice (n = 10 per treatment group) bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) and taxane-resistant (SKOV3ip2.TR) ovarian tumors. All statistical tests were two-sided.Of the 102 cancer specimens, 43 (42%) had high IL-8 expression and 59 (58%) had low or no IL-8 expression; high IL-8 expression was associated with advanced tumor stage (P = .019), high tumor grade (P = .031), and worse survival (median survival for patients with high vs low IL-8 expression: 1.62 vs 3.79 years; P < .001). Compared with empty liposomes, IL-8 siRNA-DOPC reduced the mean tumor weight by 32% (95% confidence interval [CI] = 14% to 50%; P = .03) and 52% (95% CI = 27% to 78%; P = .03) in the HeyA8 and SKOV3ip1 mouse models, respectively. In all three mouse models, treatment with IL-8 siRNA-DOPC plus the taxane docetaxel reduced tumor growth the most compared with empty liposomes (77% to 98% reduction in tumor growth; P < .01 for all). In the HeyA8 and SKOV3ip1 models, tumors from mice treated with IL-8 siRNA-DOPC alone had lower microvessel density than tumors from mice treated with empty liposomes (HeyA8: 34% lower, 95% CI = 32% to 36% lower [P = .002]; SKOV3ip1: 39% lower, 95% CI = 34% to 44% lower [P = .007]). Compared with empty liposomes, IL-8 siRNA-DOPC plus docetaxel reduced tumor cell proliferation by 35% (95% CI = 25% to 44%; P < .001) and 38% (95% CI = 28% to 48%; P < .001) in the HeyA8 and SKOV3ip1 models, respectively.Increased IL-8 expression is associated with poor clinical outcome in human ovarian carcinoma, and IL-8 gene silencing decreases tumor growth through antiangiogenic mechanisms.
New PSA Guidelines Discourage Overscreening
Authors: J. Peres
Journal: JNCI Journal of the National Cancer Institute (2011)

T he new prostate cancer screening recommendation that the U.S. Preventive Services Task Force issued in October provoked the predictable firestorm of controversy between proponents of early detection and critics who believe many screening tests have been overpromoted. But the reaction was more muted than expected, leading some to suggest that the pendulum might be swinging away from routine screening. “I ’ m extremely hopeful we ’ re near the tipping point,” said Virginia Moyer, M.D. , task force chair and professor of pediatrics at Baylor College of Medicine in Houston. “People are beginning to recognize that all early detection is not good. Just because it falls under the heading of prevention doesn ’ t mean it ’ s good without data to demonstrate the benefi t.” Moyer believes the tipping point has to do with a more sophisticated understanding of what cancer is. “The public thinks once you have a cancer cell in your body, it will progress predictably and inevitably to a terrible death,” she said. “That is simply not true of most cancers. It ’ s certainly not true of prostate cancer, not true of breast cancer, not true of most skin cancers, not true of all cervical cancers. You have a disease that is highly variable. Knowing you have cancer cells in your prostate or breast doesn ’ t mean that, unless you do something radical, you ’ re going to die of that. A signifi cant proportion of people whose disease is detected by screening never would have known about their disease in their entire lifetime. A good proportion would have died of something else before the cancer progressed to being clinically signifi cant, and many would have died of old age. “That ’ s not true for everyone,” she concedes. “Some people will have progressive, terrible disease. But unfortunately, much of the aggressive disease is rapidly progressing and, therefore, not likely to be caught by screening.” Prostate cancer is the most common malignancy in U.S. men, not counting skin cancer. The American Cancer Society expected 240,890 prostate cancer diagnoses in 2011 and expected that 33,720 men would die of the disease.
Systematic Review of Oncological Outcomes Following Surgical Management of Localised Renal Cancer
Authors: Steven MacLennan, Mari Imamura, Marie C. Lapitan, Muhammad Imran Omar, Thomas B.L. Lam, Ana M. Hilvano-Cabungcal, Pam Royle, Fiona Stewart, Graeme MacLennan, Sara J. MacLennan, Steven E. Canfield, Sam McClinton, T.R. Leyshon Griffiths, Börje Ljungberg, James N'Dow
Journal: European Urology (2012)
A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors
Authors: D. Mahadevan, R. Plummer, M.S. Squires, D. Rensvold, S. Kurtin, C. Pretzinger, T. Dragovich, J. Adams, V. Lock, D.M. Smith, D. Von Hoff, H. Calvert
Journal: Annals of Oncology (2011)
DIFFERENCES BETWEEN MITOCHONDRIA AND BACTERIA
Authors: Edmund V. Cowdry, Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1922)

A direct comparison of mitochondria and bacteria in the living condition, as well as in permanent preparations, subjected to the same influences, and viewed side by side, reveals microchemical and tinctorial differences which can only be attributed to a fundamental dissimilarity in their chemical constitution.