tbuckley/cabot-search huggingface dataset:
PHYSIOCHEMICAL AND BIOLOGICAL PROPERTIES OF THE MAJOR BASIC PROTEIN FROM GUINEA PIG EOSINOPHIL GRANULES
Authors: Gerald J. Gleich, David A. Loegering, Friedrich Kueppers, Satya P. Bajaj, Kenneth G. Mann
Journal: The Journal of Experimental Medicine (1974)

Guinea pig eosinophil granules are characterized by the presence of a basic protein of low molecular weight which accounts for greater than 50% of granule protein. This protein, termed the major basic protein (MBP), readily aggregates and becomes insoluble, and the formation of aggregates is dependent on the establishment of disulfide bonds. Analysis of concentrated preparations of MBP often revealed a series of bands which were multiples of a monomeric unit with a mol wt of approximately 11,000. Analysis of reduced and alkylated MBP on a 10% agarose column equilibrated with 6 M guanidinium chloride revealed a single polypeptide chain with a mol wt of 10,800. Amino acid analysis of the protein revealed the presence of 13% arginine, consistent with the basic character of the molecule. Four residues of tryptophan, were present, indicating that MBP is not a histone. The MBP did not increase vascular permeability when injected into the skin of guinea pigs, nor did it antagonize the effect of histamine and bradykinin in the skin. MBP also did not contract the isolated guinea pig ileum and when mixed with histamine or bradykinin did not inhibit their activity on the gut. MBP had only weak, if any, antihistaminic activity. MBP possessed weak bactericidal activity when compared to histone and then only with one strain of E. coli. MBP precipitated DNA, neutralized heparin, and activated papain. On a molar basis MBP was more active than cysteine in activating papain. These results do not point to any unique biological activity associated with MBP other than those expected of a protein as basic as it is and one which possesses reactive sulfhydryl groups. Possible functions of eosinophils based on the properties of the MBP are discussed.
Respiratory burst of intestinal macrophages in inflammatory bowel disease is mainly caused by CD14+L1+ monocyte derived cells.
Authors: J Rugtveit, G Haraldsen, A K Hogasen, A Bakka, P Brandtzaeg, H Scott
Journal: Gut (1995)

Macrophages play a crucial role in intestinal mucosal defence, forming dense subepithelial aggregates, particularly in the colon. One of their important bactericidal mechanisms is production of oxygen radicals but this may damage the intestinal epithelium, perhaps as an early step in inflammatory bowel disease (IBD). The potential for release of oxygen radicals from mucosal macrophages in IBD was measured and whether a difference exists between newly arrived (CD14+L1+) monocyte-like cells and resident macrophages (CD14(-)L1-), without or with additional priming in vitro, was investigated. Lamina propria mononuclear cells from six patients with IBD and five with a normal intestine were isolated with an ethylenediaminetetra acetic acid/collagenase/dispase technique and cultured for three days. The cells were tested with or without interferon gamma (200 U/ml) priming in the presence or absence of lipopolysaccharide (1 microgram/ml) for the last 48 hours in cultures. Samples from inflamed IBD mucosa depleted of CD14+ cells by immunomagnetic beads were compared with their undepleted counterparts and with samples from virtually normal mucosa from the same patients. The production of oxygen radicals was measured as the amount of reduced cytochrome C 2.5 hours after triggering with phorbol 12-myristate 13-acetate. The oxygen radical production in macrophages from moderately or severely inflamed mucosa was reduced by median 69% (range 22%-79%, p &lt; 0.027) after depletion of CD14+ cells, reaching a level similar to that found for virtually normal samples from the same IBD patients. Furthermore, this production did not increase significantly in mucosal macrophages from normal reference mucosa and from virtually normal or inflamed IBD mucosa after priming with interferon gamma with or without addition of lipopolysaccharide. Upregulation of a respiratory burst in subepithelial resident macrophages os not a likely pathogenetic step in IBD. The increased oxygen radical production shown by macrophages from IBD lesions can, however, be ascribed to recently extravasated CD14+L1+ monocyte-like cells. Inhibition of extravasation of these reactive cells may form part of a therapeutic approach in the future.
New National Allocation Policy for Deceased Donor Kidneys in the United States and Possible Effect on Patient Outcomes
Authors: Ajay K. Israni, Nicholas Salkowski, Sally Gustafson, Jon J. Snyder, John J. Friedewald, Richard N. Formica, Xinyue Wang, Eugene Shteyn, Wida Cherikh, Darren Stewart, Ciara J. Samana, Adrine Chung, Allyson Hart, Bertram L. Kasiske
Journal: Journal of the American Society of Nephrology (2014)

In 2013, the Organ Procurement and Transplantation Network in the United States approved a new national deceased donor kidney allocation policy that introduces the kidney donor profile index (KDPI), which gives scores of 0%-100% based on 10 donor factors. Kidneys with lower KDPI scores are associated with better post-transplant survival. Important features of the new policy include first allocating kidneys from donors with a KDPI≤20% to candidates in the top 20th percentile of estimated post-transplant survival, adding waiting time from dialysis initiation, conferring priority points for a calculated panel-reactive antibody (CPRA)>19%, broader sharing of kidneys for candidates with a CPRA≥99%, broader sharing of kidneys from donors with a KDPI>85%, eliminating the payback system, and allocating blood type A2 and A2B kidneys to blood type B candidates. We simulated the distribution of kidneys under the new policy compared with the current allocation policy. The simulation showed increases in projected median allograft years of life with the new policy (9.07 years) compared with the current policy (8.82 years). With the new policy, candidates with a CPRA>20%, with blood type B, and aged 18-49 years were more likely to undergo transplant, but transplants declined in candidates aged 50-64 years (4.1% decline) and ≥65 years (2.7% decline). These simulations demonstrate that the new deceased donor kidney allocation policy may improve overall post-transplant survival and access for highly sensitized candidates, with minimal effects on access to transplant by race/ethnicity and declines in kidney allocation for candidates aged ≥50 years.
Phagocytosis, Innate Immunity, and Host–Pathogen Specificity
Authors: Phillip Henneke, Douglas T. Golenbock
Journal: The Journal of Experimental Medicine (2004)

In mammals, phagocytosis is essential for a variety of biological events, including tissue remodeling and the continuous clearance of dying cells. Furthermore, phagocytosis represents an early and crucial event in triggering host defenses against invading pathogens, which is the focus of this
A disintegrin and metalloprotease 33 and chronic obstructive pulmonary disease pathophysiology
Authors: M. M E Gosman, H Marike Boezen, C. C van Diemen, J. B Snoeck-Stroband, T. S Lapperre, P. S Hiemstra, N. H T ten Hacken, J. Stolk, D. S Postma
Journal: Thorax (2006)

<b>Background:</b> Chronic obstructive pulmonary disease (COPD) is a respiratory disorder with increasing prevalence and mortality. It is associated with airway obstruction, increased airway hyper-responsiveness (AHR), and ongoing airway and lung inflammation dominated by CD8 lymphocytes and neutrophils. Single-nucleotide polymorphisms (SNPs) in <i>a disintegrin and metalloprotease 33</i> (<i>ADAM33</i>) gene have been associated with AHR and COPD. <b>Objective:</b> To assess whether SNPs in <i>ADAM33</i> are associated with the severity of AHR and airway inflammation in COPD. <b>Methods:</b> Eight SNPs in <i>ADAM33</i> (F+1, Q-1, S_1, S_2, ST+5, T_1, T_2, V_4) were genotyped in 111 patients with COPD (96 males, 69 current smokers, mean (standard deviation (SD)), aged 62 (8) years, median pack-years 42 (IQR 31–55), mean postbronchodilator forced expiratory volume in 1 s (FEV<sub>1</sub>)% predicted 63 (9). Provocative concentration of methacholine causing a decrease in FEV<sub>1</sub> of 20% (PC<sub>20</sub> methacholine), sputum and bronchial biopsies were collected. <b>Results:</b> Patients with the ST+5 AA genotype had more severe AHR, higher numbers of sputum inflammatory cells and CD8 cells in bronchial biopsies than patients with the GG genotype (p = 0.03, 0.05 and 0.01, respectively). CD8 cell numbers were lower in patients carrying the minor allele of SNP T_1 and T_2, and homozygotic minor variants of SNP S_2 compared with the wild type (p = 0.02, 0.01 and 0.02, respectively). <b>Conclusions:</b> This is the first study revealing that SNPs in a gene that confers susceptibility to COPD in the general population—that is, <i>ADAM33</i>—are associated with AHR and airway inflammation in COPD. These findings constitute an important step forward in linking gene polymorphisms with COPD pathophysiology, thereby possibly contributing to better treatments for this progressive and disabling disease in the future.
Development of Mammary Tumors by Conditional Expression of GLI1
Authors: Marie Fiaschi, Björn Rozell, Åsa Bergström, Rune Toftgård
Journal: Cancer Research (2009)

A diverse set of cellular defects, presumably elicited by multiple genetic alterations, underlies cancer development. Aberrant Hedgehog (Hh) signaling has recently been implicated in the development and maintenance of breast cancer. However, evidence conclusively showing that activated Hh signaling can induce mammary tumors is lacking. We now show that transgenic expression of the Hh effector protein GLI1 under the regulation of the mouse mammary tumor virus promoter, expressed in the mouse mammary gland, is associated with the appearance of hyperplastic lesions, defective terminal end buds, and tumor development. The GLI1-induced tumors are histologically heterogeneous and involve the expansion of a population of epithelial cells expressing the progenitor cell markers keratin 6 and Bmi-1. Moreover, tumor cells express genes involved in proliferation, cell survival, and metastasis. GLI1-induced tumors do not fully regress following transgene deinduction, indicating that some tumors develop and are maintained autonomously, independent of sustained transgenic GLI1 expression. The data strongly support a role of Hh/GLI signaling in breast cancer development and suggest that inhibition of this signaling pathway represents a new therapeutic opportunity for limiting tumorigenesis and early tumorigenic progression.
Improvement in liver fibrosis, functionality and hemodynamics in CCl4-cirrhotic rats after injection of the Liver Growth Factor
Authors: Juan J Díaz-Gil, Javier Muñoz, Agustín Albillos, Carmen Rúa, Celia Machín, Rafael García-Cañero, Rosa M Cereceda, María C Guijarro, Carolina Trilla, Pedro Escartín
Journal: Journal of Hepatology (1999)
Rates of Serious Infection after Changes in Regimens for Medical Abortion
Authors: Mary Fjerstad, James Trussell, Irving Sivin, E. Steve Lichtenberg, Vanessa Cullins
Journal: New England Journal of Medicine (2009)

From 2001 through March 2006, Planned Parenthood health centers throughout the United States provided medical abortion (abortion by means of medication) principally by a regimen of oral mifepristone followed 24 to 48 hours later by vaginal misoprostol. In response to concern about serious infections, in early 2006 Planned Parenthood changed the route of misoprostol administration from vaginal to buccal and required either routine provision of antibiotics or universal screening and treatment for chlamydia; in July 2007, Planned Parenthood began requiring routine treatment with antibiotics for all medical abortions.We performed a retrospective analysis assessing the rates of serious infection after medical abortion during a time when misoprostol was administered vaginally (through March 2006), as compared with rates after a change to buccal administration of misoprostol and after initiation of additional infection-reduction measures.Rates of serious infection dropped significantly after the joint change to buccal misoprostol from vaginal misoprostol and to either testing for sexually transmitted infection or routine provision of antibiotics as part of the medical abortion regimen. The rate declined 73%, from 0.93 per 1000 abortions to 0.25 per 1000 (absolute reduction, 0.67 per 1000; 95% confidence interval [CI], 0.44 to 0.94; P<0.001). The subsequent change to routine provision of antibiotics led to a further significant reduction in the rate of serious infection - a 76% decline, from 0.25 per 1000 abortions to 0.06 per 1000 (absolute reduction, 0.19 per 1000; 95% CI, 0.02 to 0.34; P=0.03).The rate of serious infection after medical abortion declined by 93% after a change from vaginal to buccal administration of misoprostol combined with routine administration of antibiotics.
Cisplatin-Induced Downregulation of OCTN2 Affects Carnitine Wasting
Authors: Cynthia S. Lancaster, Chaoxin Hu, Ryan M. Franke, Kelly K. Filipski, Shelley J. Orwick, Zhaoyuan Chen, Zhili Zuo, Walter J. Loos, Alex Sparreboom
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Carnitine is an essential cofactor for mitochondrial fatty acid oxidation that is actively reabsorbed by the luminal transporter Octn2 (Slc22a5). Because the nephrotoxic agent cisplatin causes urinary loss of carnitine in humans, we hypothesized that cisplatin may affect Octn2 function. Experimental Design: Excretion of carnitine and acetylcarnitine was measured in urine collected from mice with or without cisplatin administration. The transport of carnitine was assessed in cells that were transfected with OCT1 or OCT2. The effect of cisplatin treatment on gene expression was analyzed using a mouse GeneChip array and validated using quantitative reverse transcriptase-PCR. Results: In wild-type mice, urinary carnitine excretion at baseline was ∼3-fold higher than in mice lacking the basolateral cisplatin transporters Oct1 and Oct2 [Oct1/2(−/−) mice], indicating that carnitine itself undergoes basolateral uptake into the kidney. Transport of carnitine by OCT2, but not OCT1, was confirmed in transfected cells. We also found that cisplatin caused an increase in the urinary excretion of carnitine and acetylcarnitine in wild-type mice but not in Oct1/2(−/−) mice, suggesting that tubular transport of cisplatin is a prerequisite for this phenomenon. Cisplatin did not directly inhibit the transport of carnitine by Octn2 but downregulated multiple target genes of the transcription factor peroxisome proliferator activated receptor α, including Slc22a5, in the kidney of wild-type mice that were absent in Oct1/2(−/−) mice. Conclusion: Our study shows a pivotal role of Oct1 and Oct2 in cisplatin-related disturbances in carnitine homeostasis. We postulate that this phenomenon is triggered by deactivation of peroxisome proliferator activated receptor α and leads to deregulation of carnitine-shuttle genes. Clin Cancer Res; 16(19); 4789–99. ©2010 AACR.
Phase I Study of O<sup>6</sup>-Benzylguanine and Temozolomide Administered Daily for 5 Days to Pediatric Patients With Solid Tumors
Authors: Katherine E. Warren, Alberta A. Aikin, Madeleine Libucha, Brigitte C. Widemann, Elizabeth Fox, Roger J. Packer, Frank M. Balis
Journal: Journal of Clinical Oncology (2005)

Purpose This pediatric phase I trial of O 6 -benzylguanine (O 6 BG) and temozolomide (TMZ) on a daily schedule for 5 days, every 28 days was performed to determine the maximum-tolerated dose of TMZ when given with a biologically active dose of O 6 BG and to define the toxicity profile of the combination in children with solid tumors. Patients and Methods Patients ≤ 21 years old with refractory solid tumors were eligible. O 6 BG was administered intravenously over 60 minutes daily for 5 days. TMZ was administered orally 30 minutes after completion of each O 6 BG infusion. Starting doses of O 6 BG and TMZ were 60 mg/m 2 /d and 28 mg/m 2 /d, respectively. O 6 BG was escalated to 90 and 120 mg/m 2 /d; TMZ was subsequently escalated to 40, 55, 75, and 100 mg/m 2 /d. Cycles were repeated every 28 days. Results Forty-one patients were enrolled; 32 patients were assessable for toxicity. The combination of O 6 BG and TMZ was tolerable at TMZ doses less than half of the conventional dose of 200 mg/m 2 /d. Myelosuppression occurred sporadically at all dose levels and was the dose-limiting toxicity (DLT) at 100 mg/m 2 /d of TMZ combined with 120 mg/m 2 /d O 6 BG. Nonhematologic toxicities were generally mild. Evidence of antitumor activity was observed at 120 mg/m 2 /d O 6 BG combined with TMZ doses of 55 mg/m 2 /d and above. Conclusion The recommended doses of O 6 BG administered with TMZ on a 5-day schedule in children are 120 mg/m 2 /d of O 6 BG and 75 mg/m 2 /d of TMZ. Evidence of activity was observed at these doses. Myelosuppression was the DLT.
Human Leukemia Antigen. II. Purification&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: R Billing, P I Terasaki
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Human Leukemia Antigen. II. Purification Get access Ronald Billing, Ph. D., Ronald Billing, Ph. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul I. Terasaki, Ph. D. Paul I. Terasaki, Ph. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 6, December 1974, Pages 1639–1643, https://doi.org/10.1093/jnci/53.6.1639 Published: 01 December 1974 Article history Received: 22 July 1974 Accepted: 29 August 1974 Published: 01 December 1974
Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples
Authors: L A Thomas
Journal: Gut (2001)

Deoxycholic acid (DCA), implicated in the pathogenesis of gall stones and colorectal cancer, is mainly formed by bacterial deconjugation (cholylglycine hydrolase (CGH)) and 7 alpha-dehydroxylation (7 alpha-dehydroxylase (7 alpha-DH)) of conjugated cholic acid (CA) in the caecum/proximal colon. Despite this, most previous studies of CGH and 7 alpha-DH have been in faeces rather than in caecal contents. In bacteria, CA increases 7 alpha-DH activity by substrate-enzyme induction but little is known about CA concentrations or CA/7 alpha-DH induction in the human colon.Therefore, in fresh "faeces", and in caecal aspirates obtained during colonoscopy from 20 patients, we: (i) compared the activities of CGH and 7 alpha-DH, (ii) measured 7 alpha-DH in patients with "low" and "high" percentages of DCA in fasting serum (less than and greater than the median), (iii) studied CA concentrations in the right and left halves of the colon, and examined the relationships between (iv) 7 alpha-DH activity and CA concentration in caecal samples (evidence of substrate-enzyme induction), and (v) 7 alpha-DH and per cent DCA in serum.Although mean CGH activity in the proximal colon (18.3 (SEM 4.40) x10(-2) U/mg protein) was comparable with that in "faeces" (16.0 (4.10) x10(- 2) U/mg protein), mean 7 alpha-DH in the caecum (8.54 (1.08) x10(-4) U/mg protein) was higher (p<0.05) than that in the left colon (5.72 (0.85) x10(-4) U/mg protein). At both sites, 7 alpha-DH was significantly greater in the "high" than in the "low" serum DCA subgroups. CA concentrations in the right colon (0.94 (0.08) micromol/ml) were higher than those in the left (0.09 (0.03) micromol/ml; p<0.001) while in the caecum (but not in the faeces) there was a weak (r=0.58) but significant (p<0.005) linear relationship between 7 alpha-DH and CA concentration. At both sites, 7 alpha-DH was linearly related (p<0.005) to per cent DCA in serum. INTERPRETATION/SUMMARY: These results: (i) confirm that there are marked regional differences in bile acid metabolism between the right and left halves of the colon, (ii) suggest that caecal and faecal 7 alpha-DH influence per cent DCA in serum (and, by inference, in bile), and (iii) show that the substrate CA induces the enzyme 7 alpha-DH in the caecum.
Lactadherin Deficiency Leads to Apoptotic Cell Accumulation and Accelerated Atherosclerosis in Mice
Authors: Hafid Ait-Oufella, Kiyoka Kinugawa, Joffrey Zoll, Tabassome Simon, Jacques Boddaert, Silvia Heeneman, Olivier Blanc-Brude, Véronique Barateau, Stéphane Potteaux, Régine Merval, Bruno Esposito, Elisabeth Teissier, Mat J. Daemen, Guy Lesèche, Chantal Boulanger, Alain Tedgui, Ziad Mallat
Journal: Circulation (2007)

Background— Atherosclerosis is an immunoinflammatory disease; however, the key factors responsible for the maintenance of immune regulation in a proinflammatory milieu are poorly understood. Methods and Results— Here, we show that milk fat globule-EGF factor 8 (Mfge8, also known as lactadherin) is expressed in normal and atherosclerotic human arteries and is involved in phagocytic clearance of apoptotic cells by peritoneal macrophages. Disruption of bone marrow–derived Mfge8 in a murine model of atherosclerosis leads to substantial accumulation of apoptotic debris both systemically and within the developing lipid lesions. The accumulation of apoptotic material is associated with a reduction in interleukin-10 in the spleen but an increase in interferon-γ production in both the spleen and the atherosclerotic arteries. In addition, we report a dendritic cell-dependent alteration of natural regulatory T-cell function in the absence of Mfge8. These events are associated with a marked acceleration of atherosclerosis. Conclusions— Lack of Mfge8 in bone marrow–derived cells enhances the accumulation of apoptotic cell corpses in atherosclerosis and alters the protective immune response, which leads to an acceleration of plaque development.
Stewardship Practices of U.S. Biobanks
Authors: Gail E. Henderson, Teresa P. Edwards, R. Jean Cadigan, Arlene M. Davis, Catherine Zimmer, Ian Conlon, Bryan J. Weiner
Journal: Science Translational Medicine (2013)

Most U.S. biobanks do not create ongoing relationships with contributors but do practice stewardship over storing and sharing of specimens.
Long-Term Efficacy of a Hepatitis E Vaccine
Authors: Jun Zhang, Xue-Feng Zhang, Shou-Jie Huang, Ting Wu, Yue-Mei Hu, Zhong-Ze Wang, Hua Wang, Han-Min Jiang, Yi-Jun Wang, Qiang Yan, Meng Guo, Xiao-Hui Liu, Jing-Xin Li, Chang-Lin Yang, Quan Tang, Ren-Jie Jiang, Hui-Rong Pan, Yi-Min Li, J. Wai-Kuo Shih, Mun-Hon Ng, Feng-Cai Zhu, Ning-Shao Xia
Journal: New England Journal of Medicine (2015)

Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined.In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years.During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) [corrected]. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).