tbuckley/cabot-search huggingface dataset:
Removal of anti-Galα1,3Gal xenoantibodies with an injectable polymer
Authors: Andreas G. Katopodis, Richard G. Warner, Rudolf O. Duthaler, Markus B. Streiff, Armin Bruelisauer, Olivier Kretz, Birgit Dorobek, Elke Persohn, Hendrik Andres, Alain Schweitzer, Gebhard Thoma, Willy Kinzy, Valerie F.J. Quesniaux, Emanuele Cozzi, Hugh F.S. Davies, Rafael Mañez, David White
Journal: Journal of Clinical Investigation (2002)

Preformed and elicited Ab's against the Galalpha1,3Gal terminating carbohydrate chains (alphaGal Ab's) are the primary cause of hyperacute and acute vascular xenograft rejection in pig-to-primate transplantation. alphaGal Ab's are produced by long-lived Ab-producing cells that are not susceptible to pharmacological immunosuppression. We reasoned that antigen-specific elimination of alphaGal Ab's might be achieved in vivo by systemic administration of nonimmunogenic polyvalent alphaGal structures with high avidity for alphaGal Ab's. We devised GAS914, a soluble trisaccharide-polylysine conjugate of approximately 500 kDa that effectively competes for alphaGal binding by alphaGal IgM (IC(50), 43 nM) and IgG (IC(50), 28 nM) in vitro. Injections of GAS914 in cynomolgus monkeys, at the dose of 1 mg/kg, resulted in the immediate decrease of more than 90% of circulating alphaGal Ab's and serum anti-pig cytotoxicity. In baboons, repeated injections of GAS914 effectively reduced both circulating alphaGal Ab's and cytotoxicity over several months. Studies with [(14)C]GAS914 in rhesus monkeys and Gal(-/-) mice indicate that GAS914 binds to circulating alphaGal Ab's and that the complex is quickly metabolized by the liver and excreted by the kidney. Remarkably, posttreatment alphaGal Ab titers never exceeded pretreatment levels and no sensitization to either alphaGal or the polylysine backbone has been observed. Furthermore there was no apparent acute or chronic toxicity associated with GAS914 treatment in primates. We conclude that GAS914 may be used therapeutically for the specific removal of alphaGal Ab's.
Airway hyperresponsiveness and risk of chest symptoms in an occupational model
Authors: K Boutet, J-L Malo, H Ghezzo, D Gautrin
Journal: Thorax (2006)

<b>Background:</b> The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) remains unclear. A study was undertaken to evaluate the incidence of respiratory symptoms in a cohort of asymptomatic subjects with AHR at baseline. <b>Methods:</b> A 3 year prospective study involving methacholine challenge tests and serially administered questionnaires was undertaken in 769 apprentices exposed to high molecular weight allergens. Analyses were performed on 428 initially asymptomatic subjects. <b>Results:</b> Thirty eight subjects (8.9%) were airway hyperresponsive (PC<sub>20</sub> ⩽8 mg/ml) and asymptomatic at the start of the study. Forty four apprentices (10.3%) developed two or more respiratory symptoms unrelated to work, 13 (34.2%) in the AHR group and 31 (7.9%) in the non-AHR group (risk ratio (RR) 7.88 (95% CI 2.53 to 24.55) among subjects with AHR). The RR of developing two or more respiratory symptoms increased as the degree of PC<sub>20</sub> decreased with a significant trend (p&lt;0.001). In a multivariate analysis, AHR (RR 8.33, 95% CI 2.65 to 26.16) and self-reported rhinitis on exposure to pollen through an interaction with a family history of asthma (RR 6.3, 95% CI 1.29 to 31.89) were associated with the incidence of two or more respiratory symptoms; atopy was not a significant covariate. <b>Conclusion:</b> AHR in asymptomatic subjects is an important determinant for the development of respiratory symptoms outside the workplace among apprentices exposed to high molecular weight allergens in their training environment.
Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals.
Authors: M E Brandes, J B Allen, Y Ogawa, S M Wahl
Journal: Journal of Clinical Investigation (1991)

Systemic administration of the cytokine, TGF beta 1, profoundly antagonized the development of polyarthritis in susceptible rats. TGF beta 1 administration (1 or 5 micrograms/animal), initiated one day before an arthritogenic dose of streptococcal cell wall (SCW) fragments, virtually eliminated the joint swelling and distortion typically observed during both the acute phase (articular index, AI = 2.5 vs. 11; P less than 0.025) and the chronic phase (AI = 0 vs. 12.5) of the disease. Moreover, TGF beta 1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease. Histopathological examination of the joint revealed the systemic TGF beta 1 treatment greatly reduced inflammatory cell infiltration, pannus formation, and joint erosion. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF beta 1 reversed the leukocytosis associated with the chronic phase of the arthritis. Control animals subjected to the same TGF beta 1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment. These observations not only provide insight into the immunoregulatory effects of TGF beta, but also implicate this cytokine as a potentially important therapeutic agent.
Geographical Variation in Diabetes Prevalence and Detection in China: Multilevel Spatial Analysis of 98,058 Adults
Authors: Maigeng Zhou, Thomas Astell-Burt, Yufang Bi, Xiaoqi Feng, Yong Jiang, Yichong Li, Andrew Page, Limin Wang, Yu Xu, Linhong Wang, Wenhua Zhao, Guang Ning
Journal: Diabetes Care (2014)

OBJECTIVE To investigate the geographic variation in diabetes prevalence and detection in China. RESEARCH DESIGN AND METHODS Self-report and biomedical data were collected from 98,058 adults aged ≥18 years (90.5% response) from 162 areas spanning mainland China. Diabetes status was assessed using American Diabetes Association criteria. Among those with diabetes, detection was defined by prior diagnosis. Choropleth maps were used to visually assess geographical variation in each outcome at the provincial level. The odds of each outcome were assessed using multilevel logistic regression, with adjustment for person- and area-level characteristics. RESULTS Geographic visualization at the provincial level indicated widespread variation in diabetes prevalence and detection across China. Regional prevalence adjusted for age, sex, and urban/rural socioeconomic circumstances (SECs) ranged from 8.3% (95% CI 7.2%, 9.7%) in the northeast to 12.7% (11.1%, 14.6%) in the north. A clear negative gradient in diabetes prevalence was observed from 13.1% (12.0%, 14.4%) in the urban high-SEC to 8.7% (7.8%, 9.6%) in rural low-SEC counties/districts. Adjusting for health literacy and other person-level characteristics only partially attenuated these geographic variations. Only one-third of participants living with diabetes had been previously diagnosed, but this also varied substantively by geography. Regional detection adjusted for age, sex, and urban/rural SEC, for example, spanned from 40.4% (34.9%, 46.3%) in the north to 15.6% (11.7%, 20.5%) in the southwest. Compared with detection of 40.8% (37.3%, 44.4%) in urban high-SEC counties, detection was poorest among rural low-SEC counties at just 20.5% (17.7%, 23.7%). Person-level characteristics did not fully account for these geographic variations in diabetes detection. CONCLUSIONS Strategies for addressing diabetes risk and improving detection require geographical targeting.
Comparison of Models to Predict Nonsentinel Lymph Node Status in Breast Cancer Patients With Metastatic Sentinel Lymph Nodes: A Prospective Multicenter Study
Authors: Charles Coutant, Camille Olivier, Eric Lambaudie, Eric Fondrinier, Fréderic Marchal, François Guillemin, Nathalie Seince, Véronique Thomas, Jean Levêque, Emmanuel Barranger, Emile Darai, Serge Uzan, Gilles Houvenaeghel, Roman Rouzier
Journal: Journal of Clinical Oncology (2009)

Purpose Several models have been developed to predict nonsentinel lymph node (non-SN) status in patients with breast cancer with sentinel lymph node (SN) metastasis. The purpose of our investigation was to compare available models in a prospective, multicenter study. Patients and Methods In a cohort of 561 positive-SN patients who underwent axillary lymph node dissection, we evaluated the areas under the receiver operating characteristic curves (AUCs), calibration, rates of false negatives (FN), and number of patients in the group at low risk for non-SN calculated from nine models. We also evaluated these parameters in the subgroup of patients with micrometastasis or isolated tumor cells (ITC) in the SN. Results At least one non-SN was metastatic in 147 patients (26.2%). Only two of nine models had an AUC greater than 0.75. Three models were well calibrated. Two models yielded an FN rate less than 5%. Three models were able to assign more than a third of patients in the low-risk group. Overall, the Memorial Sloan-Kettering Cancer Center nomogram and Tenon score outperform other methods for all patients, including the subgroup of patients with only SN micrometastases or ITC. Conclusion Our study suggests that all models do not perform equally, especially for the subgroup of patients with only micrometastasis or ITC in the SN. We point out available evaluation methods to assess their performance and provide guidance for clinical practice.
SYNTHESIS OF VIRUS-SPECIFIC POLYMERS IN ADENOVIRUS-INFECTED CELLS: EFFECT OF 5-FLUORODEOXYURIDINE
Authors: John F. Flanagan, Harold S. Ginsberg
Journal: The Journal of Experimental Medicine (1962)

Biochemical synthesis in adenovirus-infected HeLa cells was studied utilizing 5-fluorodeoxyuridine (5-FUDR), a potent inhibitor of deoxyribonucleic acid production. Synthesis of saline-soluble DNA and infectious virus was completely suppressed by addition of the analogue to cells as late as 10 hours after infection. The inhibitory effect of this compound was totally reversed by addition of 10(-6)M thymidine to the culture medium. Synthesis of DNA essential for virus production began 10 hours after infection and was completed by 16 hours after infection. These data support the hypothesis that the saline-soluble DNA is a precursor of infectious virus particles. Studies of antigen production indicated that formation of virus-specific proteins was directly dependent upon synthesis of DNA.
THE PROPERTIES OF THE BACTERICIDAL SUBSTANCE IN MILK
Authors: F. S. Jones
Journal: The Journal of Experimental Medicine (1928)

Certain of the properties of the bacterial agent in milk have been studied. The substance is present in the colostrum and milk of the first few days of lactation as well as later. Its concentration varies in the secretion from various quarters of the same cow. Its activity is diminished by heat and cannot be restored again by the addition of active milk. The principle is present in whey and readily passes through the coarsest Berkefeld filter although a considerable portion is retained by N candles. The finest filter (W) completely retains it. It is adsorbed by animal charcoal but not by kaolin, kieselguhr, or bolus alba. It can be desiccated and its presence has been demonstrated in one brand of dried milk.
Preoperative MRI in Breast Cancer Grows Contentious
Authors: K. Hede
Journal: JNCI Journal of the National Cancer Institute (2009)

S ince its introduction in breast imaging, the use of magnetic resonance imaging (MRI) technology has become a source of contentiousness between its ardent supporters and its fierce critics. No sooner had consensus been reached that MRI screening for breast can cer should be restricted to high-risk women than a new controversy flared over its preoperative use in early-stage breast cancer patients. Fueling the debate is a recent fl urry of reports suggesting that MRI use increases mastectomy rates, prolongs the time from diagnosis to treatment, and may increase the rate of overdiagnosis (detection of clinically insignifi cant cancers). Staunch advocates of preoperative MRIs, however, argue that in their hands it reduces reexcision surgeries and therefore reduces costs. Most recently, in a review of more than two dozen recent studies, Nehmat Houssami, Ph.D., of Sydney Medical School, University of Sydney, Australia, and Daniel Hayes, M.D. , of the University of Michigan Comprehensive Cancer Center, Ann Arbor, conclude that little evidence exists to support the routine use of MRI in the care of newly diagnosed breast cancer patients. When the investigators pooled data from 12 primary studies on changes in surgical management based on MRI detection, they found that 11.3% of patients had more extensive surgery than initially planned and that 8.1% of women originally thought eligible for breast-conserving surgery converted to mastectomy because of MRI fi ndings of additional suspicious lesions. The review, published in CA: A Cancer Journal for Clinicians , argues that MRI could have a potentially harmful effect. “What really breaks my heart is seeing an increased rate of mastectomies after 40 years of battling over doing breast conservation,” said Hayes. “I lived through the mastectomy versus breast conservation wars . . . but because of randomized trials, and surgeons willing to challenge their [own] dogma, and because we chose appropriate endpoints, we convinced ourselves that breast conservation was every bit as good as a mastectomy. And now we are reversing those great successes.”
Immunological Memory
Authors: Dominic F. Kelly, Andrew J. Pollard, E. Richard Moxon
Journal: JAMA (2005)

Protein-polysaccharide conjugate vaccines that protect against Haemophilus influenzae type b (Hib), serogroup C Neisseria meningitidis, and multiple capsular serotypes of Streptococcus pneumoniae have had a major impact on invasive bacterial disease in childhood when incorporated into routine infant immunization schedules. However, effectiveness data from the United Kingdom suggest that primary infant immunization alone may not be associated with long-term protection. Both immunological priming and antibody persistence are important aspects of long-term protection induced by these vaccines. An improved understanding of the immunobiology of the B-cell response to these vaccines may direct development of immunization strategies that provide sustained protection.
t(8;14;18): A 3-way chromosome translocation in two patients with Burkitt's lymphoma/leukemia
Authors: Delong Liu, Josif Shimonov, Suneeta Primanneni, Yongrong Lai, Tauseef Ahmed, Karen Seiter
Journal: Molecular Cancer (2007)

Burkitt's lymphoma (BL) is a heterogeneous group of highly aggressive mature B-cell malignancies. It is characterized by a high rate of turnover of malignant cells and deregulation of the c-myc gene. It is typically associated with a t(8;14) translocation. Dual translocation of t(8;14) (c-myc) and t(14;18) (bcl-2) was reported to be associated with extremely poor prognosis. This study reports a novel t(8;14;18) triple translocation in two patients with Burkitt's lymphoma.
Association of Prenatal and Childhood Blood Lead Concentrations with Criminal Arrests in Early Adulthood
Authors: John Paul Wright, Kim N Dietrich, M. Douglas Ris, Richard W Hornung, Stephanie D Wessel, Bruce P Lanphear, Mona Ho, Mary N Rae
Journal: PLoS Medicine (2008)

Childhood lead exposure is a purported risk factor for antisocial behavior, but prior studies either relied on indirect measures of exposure or did not follow participants into adulthood to examine the relationship between lead exposure and criminal activity in young adults. The objective of this study was to determine if prenatal and childhood blood lead concentrations are associated with arrests for criminal offenses.Pregnant women were recruited from four prenatal clinics in Cincinnati, Ohio if they resided in areas of the city with a high concentration of older, lead-contaminated housing. We studied 250 individuals, 19 to 24 y of age, out of 376 children who were recruited at birth between 1979 and 1984. Prenatal maternal blood lead concentrations were measured during the first or early second trimester of pregnancy. Childhood blood lead concentrations were measured on a quarterly and biannual basis through 6.5 y. Study participants were examined at an inner-city pediatric clinic and the Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio. Total arrests and arrests for offenses involving violence were collected from official Hamilton County, Ohio criminal justice records. Main outcomes were the covariate-adjusted rate ratios (RR) for total arrests and arrests for violent crimes associated with each 5 microg/dl (0.24 micromol/l) increase in blood lead concentration. Adjusted total arrest rates were greater for each 5 microg/dl (0.24 micromol/l) increase in blood lead concentration: RR = 1.40 (95% confidence interval [CI] 1.07-1.85) for prenatal blood lead, 1.07 (95% CI 0.88-1.29) for average childhood blood lead, and 1.27 (95% CI 1.03-1.57) for 6-year blood lead. Adjusted arrest rates for violent crimes were also greater for each 5 microg/dl increase in blood lead: RR = 1.34 (95% CI 0.88-2.03) for prenatal blood lead, 1.30 (95% CI 1.03-1.64) for average childhood blood lead, and 1.48 (95% CI 1.15-1.89) for 6-year blood lead.Prenatal and postnatal blood lead concentrations are associated with higher rates of total arrests and/or arrests for offenses involving violence. This is the first prospective study to demonstrate an association between developmental exposure to lead and adult criminal behavior.
Ammonia production by intestinal bacteria
Authors: A. Vince, A. M. Dawson, N. Park, F. O'Grady
Journal: Gut (1973)

Bacterial growth and the production of ammonia from urea and by deamination of peptone has been examined at various pHs in both conventional static bacterial cultures and in a continuous cultivation system. Growth occurred on primary testing of 93 out of 100 strains of aerobic Gram-negative bacteria at pH 5, and 48 out of 50 strains of Esch. coli at pH 4.6. Hydrolysis of urea by Proteus mirabilis decreased steadily from pH 7.2 to pH 5.3; below pH 5.3 little hydrolysis occurred. Ammonia production from peptones by Esch. coli decreased from pH 7.2 to pH 4.6. Considerable variation was noted in the ability of different strains to produce ammonia. Experiments with cultures containing both Esch. coli and Pr. mirabilis showed that more ammonia was produced at low pH than was produced by cultures of single organisms. At low pH reduction in the count of organisms was not found to be an essential prerequisite for reduction of ammonia formation.
Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol
Authors: Pál Pacher, Alex Nivorozhkin, Csaba Szabó
Journal: Pharmacological Reviews (2006)

The prototypical xanthine oxidase (XO) inhibitor allopurinol, has been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades. More recent data indicate that XO also plays an important role in various forms of ischemic and other types of tissue and vascular injuries, inflammatory diseases, and chronic heart failure. Allopurinol and its active metabolite oxypurinol showed considerable promise in the treatment of these conditions both in experimental animals and in small-scale human clinical trials. Although some of the beneficial effects of these compounds may be unrelated to the inhibition of the XO, the encouraging findings rekindled significant interest in the development of additional, novel series of XO inhibitors for various therapeutic indications. Here we present a critical overview of the effects of XO inhibitors in various pathophysiological conditions and also review the various emerging therapeutic strategies offered by this approach.
The Role of Autophagy in Vascular Biology
Authors: Samuel C. Nussenzweig, Subodh Verma, Toren Finkel
Journal: Circulation Research (2015)

There is increasing interest in the role of autophagic flux in maintaining normal vessel wall biology and a growing suspicion that autophagic dysregulation may be a common pathway through which vascular aging and associated pathologies develop. Within endothelial and smooth muscle cells, diverse but important triggers that range from oxidized lipids to β-amyloid seem to stimulate autophagosome formation potently. In addition, emerging evidence links autophagy to a wide array of vascular processes ranging from angiogenesis to calcification of the vessel wall. Alterations in autophagic flux are also increasingly being implicated in disease processes that include both atherosclerosis and pulmonary hypertension. Finally, recent insights point toward an important role of autophagy in the paracrine regulation of vasoactive substances from the endothelium. Here, we review the progress in understanding how autophagy can contribute to vascular biology and the emerging strategies to target this process for therapeutic benefit.
Relationship between HLA alleles and cytomegalovirus infection after allogeneic hematopoietic stem cell transplant
Authors: Yolande Chen, Vanderson Rocha, Henrique Bittencourt, Catherine Scieux, Pascale Loiseau, Hélène Espérou, Agnès Devergie, Philippe Guardiola, Gérard Socié, Sylvie Chevret, Dominique Charron, Eliane Gluckman, Patricia Ribaud
Journal: Blood (2001)
KEAP1-NRF2 complex in ischemia-induced hepatocellular damage of mouse liver transplants
Authors: Bibo Ke, Xiu-Da Shen, Yu Zhang, Haofeng Ji, Feng Gao, Shi Yue, Naoko Kamo, Yuan Zhai, Masayuki Yamamoto, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski
Journal: Journal of Hepatology (2013)
Ultrasonographic and Biochemical Markers of Human Fetal Cardiac Dysfunction in Placental Insufficiency
Authors: Kaarin Mäkikallio, Olli Vuolteenaho, Pentti Jouppila, Juha Räsänen
Journal: Circulation (2002)

Background — Placental insufficiency may lead to fetal cardiovascular compromise. We sought to determine whether ultrasonographic parameters of fetal cardiovascular function correlate with umbilical arterial levels of biochemical markers of myocardial dysfunction and damage in placental insufficiency. Methods and Results — In 48 fetuses with placental insufficiency, umbilical artery blood was obtained at delivery for assessment of N -terminal peptide of proatrial natriuretic peptide (NT-proANP) and cardiac troponin-T (cTnT). Group 1 fetuses (n=12) had normal NT-proANP and cTnT serum concentrations. Group 2 fetuses (n=25) showed increased NT-proANP (&gt;1145 pmol/L) and normal cTnT values. Group 3 fetuses (n=11) had increased NT-proANP and cTnT (&gt;0.10 ng/mL) levels. The ultrasonographic parameters of fetal cardiovascular function were compared between the groups. Pulsatility indices for veins of the ductus venosus, left hepatic vein, and inferior vena cava correlated significantly with NT-proANP levels. In group 3, ductus venosus, left hepatic vein, and inferior vena cava pulsatility indices for veins were higher ( P &lt;0.01) than in groups 1 and 2. The proportion of left ventricular cardiac output of combined cardiac output was greater ( P &lt;0.05) and that of right ventricle was smaller ( P &lt;0.05) in group 3 than in group 2. In group 3, tricuspid regurgitation was noted most often ( P &lt;0.05), and right ventricular fractional shortening was less ( P &lt;0.01) than in group 2. Conclusions — Pulsatility in human fetal systemic veins correlated significantly with the cardiac secretion of ANP. Fetuses with myocardial damage demonstrate increased systemic venous pressure, a change in the distribution of cardiac output toward the left ventricle, and a rise in right ventricular afterload.