tbuckley/cabot-search huggingface dataset:
IP-10 and Mig Production by Glomerular Cells in Human Proliferative Glomerulonephritis and Regulation by Nitric Oxide
Authors: Paola Romagnani, Elena Lazzeri, Laura Lasagni, Carmelo Mavilia, Chiara Beltrame, Michela Francalanci, Mario Rotondi, Francesco Annunziato, Lucia Maurenzig, Lorenzo Cosmi, Grazia Galli, Maurizio Salvadori, Enrico Maggi, Mario Serio
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. High levels of expression of mRNA and protein for the chemokines interferon-γ (IFN-γ)-inducible protein of 10 kD (IP-10) (CXCL10) and the monokine induced by IFN-γ (Mig) (CXCL9) were observed, by using in situ hybridization and immunohistochemical analyses, in kidney biopsy specimens from patients with glomerulonephritis (GN), particularly those with membranoproliferative or crescentic GN, but not in normal kidneys. Double-immunostaining or combined in situ hybridization and immunohistochemical analyses for IP-10, Mig, and proliferating cell nuclear antigen (PCNA) or α-smooth muscle actin (α-SMA) revealed that IP-10 and Mig production by resident glomerular cells was a selective property of glomeruli in which mesangial cells demonstrated active proliferation. IP-10 and Mig mRNA and protein were also expressed by primary cultures of human mesangial cells and human visceral epithelial cells after stimulation with IFN- γ or with IFN-γ plus tumor necrosis factor-α (TNF-α) (which produced greater stimulation). The induction of IP-10 and Mig mRNA and protein expression by IFN-γ plus TNF-α was strongly inhibited by nitric oxide (NO) donors, such as sodium nitroprusside or S-nitroso-N-acetylpenicillamine, but not by cGMP analogues. Electrophoretic mobility shift assays demonstrated that NO donors repressed IP-10 gene transcription induced by IFN-γ plus TNF-α through the inhibition of NF-κB activation. These data demonstrate that resident glomerular cells in kidneys of patients with proliferative GN produce large amounts of IP-10 and Mig, which may play important pathogenic roles in this disease. These data also indicate that the production of IP-10 and Mig by human mesangial cells can be downregulated by NO donors through cGMP-independent inhibition of NF-κB activation.
Google unveils a glimpse of allergic rhinitis in the real world
Authors: M.-G. Kang, W.-J. Song, S. Choi, H. Kim, H. Ha, S.-H. Kim, S.-H. Cho, K.-U. Min, S. Yoon, Y.-S. Chang
Journal: Allergy (2014)

Google Trends (GT) is a Web-based surveillance tool used to explore the searching trends of specific queries on Google. Recent studies have suggested the utility of GT in predicting outbreaks of influenza and other diseases. However, this utility has not been thoroughly evaluated for allergic diseases. Therefore, we investigated the utility of GT for predicting the epidemiology of allergic rhinitis. In the USA, GT for allergic rhinitis showed repetitive seasonality that peaked in late April and early May and then rapidly decreased, and a second small peak occurred in September. These trends are highly correlated with the searching trends for other queries such as 'pollen count', antihistamines such as loratadine and cetirizine (all r > 0.88 and all P < 0.001), and even the total pollen count collected from 21 pollen counters across the USA (r = 0.928, P < 0.001). Google Trends for allergic rhinitis was similar to the monthly changes in rhinitis symptoms according to the US National Health and Nutrition Examination Survey III, sales for Claritin(®) and all over-the-counter antihistamines, and the number of monthly page views of 'claritin.com'. In conclusion, GT closely reflects the real-world epidemiology of allergic rhinitis in the USA and could potentially be used as a monitoring tool for allergic rhinitis.
The effects of ammonia and portal-systemic shunting on brain metabolism, neurotransmission and intracranial hypertension in hyperammonaemia-induced encephalopathy
Authors: Birgit A.P.M. Vogels, Bob van Steynen, Martinus A.W. Maas, George G.A. Jörning, Robert A.F.M. Chamuleau
Journal: Journal of Hepatology (1997)
Safety and Efficacy of VCN-01, an Oncolytic Adenovirus Combining Fiber HSG-Binding Domain Replacement with RGD and Hyaluronidase Expression
Authors: Alba Rodríguez-García, Marta Giménez-Alejandre, Juan J. Rojas, Rafael Moreno, Miriam Bazan-Peregrino, Manel Cascalló, Ramon Alemany
Journal: Clinical Cancer Research (2014)

Tumor targeting upon intravenous administration and subsequent intratumoral virus dissemination are key features to improve oncolytic adenovirus therapy. VCN-01 is a novel oncolytic adenovirus that combines selective replication conditional to pRB pathway deregulation, replacement of the heparan sulfate glycosaminoglycan putative-binding site KKTK of the fiber shaft with an integrin-binding motif RGDK for tumor targeting, and expression of hyaluronidase to degrade the extracellular matrix. In this study, we evaluate the safety and efficacy profile of this novel oncolytic adenovirus.VCN-01 replication and potency were assessed in a panel of tumor cell lines. VCN-01 tumor-selective replication was evaluated in human fibroblasts and pancreatic islets. Preclinical toxicity, biodistribution, and efficacy studies were conducted in mice and Syrian hamsters.Toxicity and biodistribution preclinical studies support the selectivity and safety of VCN-01. Antitumor activity after intravenous or intratumoral administration of the virus was observed in all tumor models tested, including melanoma and pancreatic adenocarcinoma, both in immunodeficient mice and immunocompetent hamsters.Oncolytic adenovirus VCN-01 characterized by the expression of hyaluronidase and the RGD shaft retargeting ligand shows an efficacy-toxicity prolife in mice and hamsters by intravenous and intratumoral administration that warrants clinical testing.
Health Care Provider-Directed Intervention to Increase Colorectal Cancer Screening Among Veterans: Results of a Randomized Controlled Trial
Authors: M. Rosario Ferreira, Nancy C. Dolan, Marian L. Fitzgibbon, Terry C. Davis, Nicolle Gorby, Lisa Ladewski, Dachao Liu, Alfred W. Rademaker, Franklin Medio, Brian P. Schmitt, Charles L. Bennett
Journal: Journal of Clinical Oncology (2005)

Colorectal cancer screening is the most underused cancer screening tool in the United States. The purpose of this study was to test whether a health care provider-directed intervention increased colorectal cancer screening rates.The study was a randomized controlled trial conducted at two clinic firms at a Veterans Affairs Medical Center. The records of 5,711 patients were reviewed; 1,978 patients were eligible. Eligible patients were men aged 50 years and older who had no personal or family history of colorectal cancer or polyps, had not received colorectal cancer screening, and had at least one visit to the clinic during the study period. Health care providers in the intervention firm attended a workshop on colorectal cancer screening. Every 4 to 6 months, they attended quality improvement workshops where they received group screening rates, individualized confidential feedback, and training on improving communication with patients with limited literacy skills. Medical records were reviewed for colorectal cancer screening recommendations and completion. Literacy level was assessed in a subset of patients.Colorectal cancer screening was recommended for 76.0% of patients in the intervention firm and for 69.4% of controls (P = .02). Screening tests were completed by 41.3% of patients in the intervention group versus 32.4% of controls (P = .003). Among patients with health literacy skills less than ninth grade, screening was completed by 55.7% of patients in the intervention group versus 30% of controls (P < .01).A provider-directed intervention with feedback on individual and firm-specific screening rates significantly increased both recommendations and colorectal cancer screening completion rates among veterans.
Determinants of Human Immunodeficiency Virus Type 1 Escape from the Primary CD8+ Cytotoxic T Lymphocyte Response
Authors: Nicola A. Jones, Xiping Wei, Darren R. Flower, MaiLee Wong, Franziska Michor, Michael S. Saag, Beatrice H. Hahn, Martin A. Nowak, George M. Shaw, Persephone Borrow
Journal: The Journal of Experimental Medicine (2004)

CD8+ cytotoxic T lymphocytes (CTLs) play an important role in containment of virus replication in primary human immunodeficiency virus (HIV) infection. HIV's ability to mutate to escape from CTL pressure is increasingly recognized; but comprehensive studies of escape from the CD8 T cell response in primary HIV infection are currently lacking. Here, we have fully characterized the primary CTL response to autologous virus Env, Gag, and Tat proteins in three patients, and investigated the extent, kinetics, and mechanisms of viral escape from epitope-specific components of the response. In all three individuals, we observed variation beginning within weeks of infection at epitope-containing sites in the viral quasispecies, which conferred escape by mechanisms including altered peptide presentation/recognition and altered antigen processing. The number of epitope-containing regions exhibiting evidence of early CTL escape ranged from 1 out of 21 in a subject who controlled viral replication effectively to 5 out of 7 in a subject who did not. Evaluation of the extent and kinetics of HIV-1 escape from &amp;gt;40 different epitope-specific CD8 T cell responses enabled analysis of factors determining escape and suggested that escape is restricted by costs to intrinsic viral fitness and by broad, codominant distribution of CTL-mediated pressure on viral replication.
Note on a Peculiar Post-Mortem Appearance of the Cardiac Walls
Authors: F. P. Weber
Journal: BMJ (1897)

firm, is located rather higher than usual, and far back.The os is not patulous.The body of the uterus, enlarged to the extent of an eight or nine weeks pregnancy, is detected readily by bimanual examination.On September 24th, labour-like pain was experienced, and a mass was expelled from the vagina.This mass, which was of the size of an orange, contained an embryo of about i4 inch in length and il ounce of dark biliary-looking fluid.2REMARKS.-Inthis case the death of the embryo was pro- bably due to defective evolutional power in the fecundated ovum, and no external haemorrhage occurred for three months after its death.CASE IV, Retention of a 3 or a 32 Months' Fa?tus for -Five Months after its Death.-R.S., aged 40, and married fourteen years, had had five children and two miscarriages.,The miscarriages occurred between the births of the fourth and fifth children, and the last child was born in I890.She ceased menstruating on August 26th, I895, and thereafter there was complete amenorrhoea until February 12th, 1896, when a dark blood-coloured discharge from the vagina was observed.On March i8th, 1896, the patient came under my care, and she stated that daily since February 12th the blood-coloured discharge from the vagina had been noted.She had complained of no pain.On March i8th the following notes were made." Abdominal examination is negative.Vaginal examination:The cervix, which is soft, is located towards the left wall of the pelvis, and the os is slightly open.By bimanual examin- ation the body of the uterus is readily defined, and is equal in size to about a ten weeks pregnancy.The consistence of the uterus is doughy, and its right half is lobulated.No colostrum could be obtained from the breasts."From March i8th until April 24th there was daily a blood- coloured discharge from the vagina.On April 24th with a slight labour-like pain, a mass was expelled from the vagina.This mass contained what appeared to be a 3 or a 32 months fcetus, and, although the membranes were perfectly intact, the sac contained no fluid.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites
Authors: O Sorg, M Zennegg, P Schmid, R Fedosyuk, R Valikhnovskyi, O Gaide, V Kniazevych, J-H Saurat
Journal: The Lancet (2009)
International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature: TABLE 1
Authors: Jerold Chun, Timothy Hla, Kevin R. Lynch, Sarah Spiegel, Wouter H. Moolenaar
Journal: Pharmacological Reviews (2010)

Lysophospholipids are cell membrane-derived lipids that include both glycerophospholipids such as lysophosphatidic acid (LPA) and sphingoid lipids such as sphingosine 1-phosphate (S1P). These and related molecules can function in vertebrates as extracellular signals by binding and activating G protein-coupled receptors. There are currently five LPA receptors, along with a proposed sixth (LPA<sub>1</sub>-LPA<sub>6</sub>), and five S1P receptors (S1P<sub>1</sub>-S1P<sub>5</sub>). A remarkably diverse biology and pathophysiology has emerged since the last review, driven by cloned receptors and targeted gene deletion ("knockout") studies in mice, which implicate receptor-mediated lysophospholipid signaling in most organ systems and multiple disease processes. The entry of various lysophospholipid receptor modulatory compounds into humans through clinical trials is ongoing and may lead to new medicines that are based on this signaling system. This review incorporates IUPHAR Nomenclature Committee guidelines in updating the nomenclature for lysophospholipid receptors (http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=36).
Identification of a Chlamydial Protease–Like Activity Factor Responsible for the Degradation of Host Transcription Factors
Authors: Guangming Zhong, Peiyi Fan, Hezhao Ji, Feng Dong, Yanqing Huang
Journal: The Journal of Experimental Medicine (2001)

Microbial pathogens have been selected for the capacity to evade or manipulate host responses in order to survive after infection. Chlamydia, an obligate intracellular pathogen and the causative agent for many human diseases, can escape T lymphocyte immune recognition by degrading host transcription factors required for major histocompatibility complex (MHC) antigen expression. We have now identified a chlamydial protease- or proteasome-like activity factor (CPAF) that is secreted into the host cell cytosol and that is both necessary and sufficient for the degradation of host transcription factors RFX5 and upstream stimulation factor 1 (USF-1). The CPAF gene is highly conserved among chlamydial strains, but has no significant overall homology with other known genes. Thus, CPAF represents a unique secreted protein produced by an obligate intracellular bacterial pathogen to interfere with effective host adaptive immunity.
Sex-specific associations between cortisol and birth weight in pregnancies complicated by asthma are not due to differential glucocorticoid receptor expression
Authors: N. A. Hodyl, H. Wyper, A. Osei-Kumah, N. Scott, V. E. Murphy, P. Gibson, R. Smith, V. L. Clifton
Journal: Thorax (2010)

<h3>Background</h3> Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids. <h3>Methods</h3> Pregnant women with mild asthma (n=52), moderate–severe asthma (n=71) and without asthma (n=51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed. <h3>Results</h3> Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p=0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r=−0.286, p=0.017) and, despite a decrease in placental GR mRNA (p=0.003), placental GRα protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment. <h3>Conclusions</h3> The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression; however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or post-translational modifications.
Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD
Authors: Tamara Isakova, Joachim H Ix, Stuart M Sprague, Kalani L Raphael, Linda Fried, Jennifer J Gassman, Dominic Raj, Alfred K Cheung, John W Kusek, Michael F Flessner, Myles Wolf, Geoffrey A Block
Journal: Journal of the American Society of Nephrology (2015)

Patients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3-4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE study.
Early Surgery versus Conventional Treatment for Infective Endocarditis
Authors: Duk-Hyun Kang, Yong-Jin Kim, Sung-Han Kim, Byung Joo Sun, Dae-Hee Kim, Sung-Cheol Yun, Jong-Min Song, Suk Jung Choo, Cheol-Hyun Chung, Jae-Kwan Song, Jae-Won Lee, Dae-Won Sohn
Journal: New England Journal of Medicine (2012)

The timing and indications for surgical intervention to prevent systemic embolism in infective endocarditis remain controversial. We conducted a trial to compare clinical outcomes of early surgery and conventional treatment in patients with infective endocarditis.
Reduced expression of the αβ T-cell antigen receptorby alveolar T-cells
Authors: E. Yamaguchi, A. Itoh, K. Furuya, N. Hizawa, N. Ohnuma, N. Kodama, J. Kojima, Y. Kawakami
Journal: European Respiratory Journal (1999)

A previous study revealed that reduced expression (modulation) of the CD3 antigen is a common characteristic of alveolar T-cells in health and disease. As CD3 molecules are noncovalently bound to T-cell antigen receptors (TCR), it was hypothesized that modulation of TCR was also a feature of alveolar T-cells. To demonstrate this, lymphocytes from bronchoalveolar lavage fluid were stained with an anti-alphabeta TCR antibody and analysed by flow cytometry. The expression of alphabeta TCR by alveolar T-cells was evaluated by calculating mean fluorescence intensity (MFI) and was compared with alphabeta TCR expression by autologous blood T-cells. As anticipated from a previous study, modulation of TCR was observed not only in healthy volunteers but also in patients with pulmonary sarcoidosis, other pulmonary diseases, and nonpulmonary diseases. There were no significant differences in MFI of alveolar T-cells among the study groups. The degree of modulation assessed by the difference of MFI between blood and alveolar T-cells was greater for CD4+ cells than for CD8+ cells owing to the higher MFI of CD4+ blood T-cells. Coculture of alveolar macrophages with blood T-cells in vitro induced partial modulation of TCR. These results demonstrate the ubiquity of modulation of T-cell receptors on alveolar T-cells and suggest, in contrast to a previous report by other investigators that it is caused by some nonantigenic mechanism possibly inherent in the alveolar milieu. The implications of this phenomenon in in vivo immune responses of the lung need to be examined.
Cardiovascular Calcifications in Uremic Patients
Authors: Ge[Combining Acute Accent]rard M. London
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Cardiovascular disease is the leading cause of mortality among patients with ESRD (chronic kidney disease stage 5). Left ventricular hypertrophy and arterial diseases are the two principal risk factors for cardiovascular mortality in hemodialysis patients. Epidemiologic studies show that damage to large conduit arteries contributes to morbidity and mortality in patients with chronic kidney disease. Atherosclerosis is primarily an intimal disease characterized by the presence of plaques and occlusive lesions. Although atherosclerosis is the most frequent underlying cause of cardiovascular disease in patients with ESRD, it represents only one form of structural response to metabolic and hemodynamic alterations that interfere with the process of aging. Arterial alterations in ESRD include nonocclusive arterial remodeling accompanying the growing hemodynamic burden and humoral abnormalities that are associated with chronic uremia. The consequences of these alterations are different from those attributed to atherosclerotic plaques and are characterized principally by hardening (stiffening) of arteries. Arteriosclerosis, characterized by stiffening of the aorta and large capacitative arteries, is a major determinant of left ventricular pressure overload and of abnormal coronary perfusion. Atherosclerosis and arteriosclerosis are frequently comorbid and characterized by a high degree of both intimal and medial calcifications in patients with ESRD. The extent of calcifications and the degree of arterial stiffening are independent predictors of mortality. Studies in patients with ESRD have shown that attenuation of arterial stiffness can have a favorable effect, associated with regression of left ventricular hypertrophy, on survival. Calcium-free, metal-free phosphate binders such as sevelamer can reduce calcification scores. E-mail: [email protected]
Reproducibility in Science
Authors: C. Glenn Begley, John P.A. Ioannidis
Journal: Circulation Research (2014)

Medical and scientific advances are predicated on new knowledge that is robust and reliable and that serves as a solid foundation on which further advances can be built. In biomedical research, we are in the midst of a revolution with the generation of new data and scientific publications at a previously unprecedented rate. However, unfortunately, there is compelling evidence that the majority of these discoveries will not stand the test of time. To a large extent, this reproducibility crisis in basic and preclinical research may be as a result of failure to adhere to good scientific practice and the desperation to publish or perish. This is a multifaceted, multistakeholder problem. No single party is solely responsible, and no single solution will suffice. Here we review the reproducibility problems in basic and preclinical biomedical research, highlight some of the complexities, and discuss potential solutions that may help improve research quality and reproducibility.