tbuckley/cabot-search huggingface dataset:
Role of Blood Pressure Targets and Specific Antihypertensive Agents Used to Prevent Diabetic Nephropathy and Delay Its Progression
Authors: Giovanni F.M. Strippoli, Maria C. Craig, Francesco P. Schena, Jonathan C. Craig
Journal: Journal of the American Society of Nephrology (2006)

This study evaluated the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria and the evidence supporting equivalent use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) in patients with diabetes and micro- or macroalbuminuria. A systematic review was conducted by searching for randomized controlled trials (RCT) of antihypertensive agent versus placebo or another agent in hypertensive or normotensive patients with diabetes and no nephropathy and RCT of ACEi or ARB in patients with diabetic nephropathy. Medline, Embase, the Cochrane Controlled Trials Register, conference proceedings, and contact with investigators were used to identify available evidence. Two investigators independently extracted data and assessed quality of trials. Sixteen RCT (7603 patients) of antihypertensive agents conducted in patients with diabetes and no nephropathy and 43 (7739 patients) of ACEi or ARB in patients with diabetic nephropathy were identified. A significant reduction in the risk for developing microalbuminuria in patients who had diabetes with no nephropathy was demonstrated for ACEi only (six trials, 3840 patients; relative risk [RR] 0.60; 95% confidence interval [CI] 0.43 to 0.84), and in patients with diabetic nephropathy, existing RCT have shown a survival benefit of ACEi (20 trials, 2383 patients; RR 0.79; 95% CI 0.63 to 0.99; P = 0.04) but not ARB (four trials, 3329 patients; RR 0.99; 95% CI 0.85 to 1.17). On the basis of available RCT evidence, ACEi are the only agents with proven renal benefit in patients who have diabetes with no nephropathy and the only agents with proven survival benefit in patients who have diabetes with nephropathy.
Union calls for new health and safety tsar to reduce deaths in the workplace
Authors: A. O'Dowd
Journal: BMJ (2010)

A health and safety tsar for the UK should be appointed to help tackle the growing problem of tens of thousands of deaths caused by the workplace each year, says the country’s leading trade union body.

In a new report the Trades Union Congress (TUC) says more than 20 000 people in the UK are killed prematurely by their work every year.

For the report the TUC said it analysed the most conservative official safety figures available, which showed that at least 20 000 people die early as a result of their work every year through occupational cancers, lung disorders, exposure to fumes or chemicals, and fatal traffic incidents.

Although the Health and Safety Executive, the country’s watchdog for health and safety, estimates that more than 8000 deaths are caused each year by occupational cancers, the …
The predictive and prognostic value of circulating endothelial cells in advanced colorectal cancer patients receiving first-line chemotherapy and bevacizumab
Authors: L.H.J. Simkens, J. Tol, L.W.M.M. Terstappen, S. Teerenstra, C.J.A. Punt, I.D. Nagtegaal
Journal: Annals of Oncology (2010)
Risk of Tuberculosis after Recent Exposure. A 10-Year Follow-up Study of Contacts in Amsterdam
Authors: Rosa Sloot, Maarten F. Schim van der Loeff, Peter M. Kouw, Martien W. Borgdorff
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The lifetime risk of tuberculosis (TB) for infected contacts is often mentioned to be 5-10%, but these estimates are based on studies conducted decades ago, and thus may not reflect current epidemiologic conditions.To estimate the risk of TB among contacts with evidence of infection and to compare this with estimates often stated in the literature.A retrospective cohort study was performed using records on contacts of pulmonary TB patients at the Public Health Service Amsterdam, 2002-2011. The Public Health Service Amsterdam TB electronic registration system identified TB cases during follow-up until October 2012; these were defined as coprevalent if diagnosed less than or equal to 180 days and incident if diagnosed greater than 180 days after TB diagnosis of index patient. Cumulative TB risk was estimated with Kaplan-Meier curves.Of 9,332 contacts of pulmonary TB patients, 4,774 were screened for latent TB infection (LTBI) of whom 739 (16%) had evidence of infection. Among these the 5-year Kaplan-Meier TB cumulative risk was 9.5% (95% confidence interval, 7.5-11.9). This varied by age: 33.3% of 36 contacts aged less than 5 years, 19.1% of 84 contacts aged 5-14 years, and 6.7% of 619 contacts aged greater than or equal to 15 years (log rank, P < 0.001). Of 739 contacts with evidence of infection, 57 had coprevalent TB and 14 developed incident TB. Of patients without coprevalent TB but with LTBI diagnosis, 45% received preventive therapy. Five-year risk of incident TB was 2.4% (95% confidence interval, 1.2-4.7) among contacts with LTBI who did not start preventive therapy.Five-year risk of TB among contacts with evidence of infection was higher compared with older estimates, and differed considerably by age. Incidence of TB among contacts with LTBI was low, suggesting limited impact may be expected of expanding preventive therapy.
Renin gene expression in human kidney biopsies from patients with glomerulonephritis or graft rejection.
Authors: J Wagner, S Volk, C C Haufe, A Ciechanowicz, M Paul, E Ritz
Journal: Journal of the American Society of Nephrology (1995)

The expression of renin mRNA was determined by a quantitative polymerase chain reaction assay in 27 human kidney samples: (1) 15 biopsies of patients with glomerulonephritis with or without angiotensin-converting enzyme inhibitor (ACEI) treatment; (2) biopsies of six renal allografts with graft rejection; and (3) six biopsy samples from unaffected parts of tumor nephrectomy specimens as controls. After isolation of RNA, 0.5 to 1 microgram of total RNA was used for reverse transcription to generate cDNA. The human renin gene was subsequently amplified by the use of two primers spanning the second and third exons. Renin expression was quantified with a renin cDNA mutant as the internal standard. It exhibited the same primer binding sites as the endogenous gene but carried a 155-basepair deletion, thus yielding a shorter amplification product. The number of glomeruli was counted by microscopic transillumination immediately after biopsy (median, 9 per biopsy; range, 2 to 23). Renin mRNA was expressed as femtograms of renin mRNA per glomerulus. Renin gene expression was lower in glomerulonephritic patients without ACEI treatment compared with that in control tumor nephrectomy samples, i.e., 63 +/- 20 (N = 7) versus 250 +/- 50 fg (N = 6) of renin mRNA/glomerulus, (P < 0.02), although plasma renin concentration in the glomerulonephritic patients was in the normal range. Significantly higher renin mRNA expression was found in glomerulonephritic patients treated with ACEI, i.e., 210 +/- 50 (N = 8) compared with 63 +/- 20 (N = 7) fg of renin mRNA/glomerulus in patient not treated with ACEI (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Tumor Suppressor <i>CHK2</i>: Regulator of DNA Damage Response and Mediator of Chromosomal Stability
Authors: Ailine Stolz, Norman Ertych, Holger Bastians
Journal: Clinical Cancer Research (2010)

Abstract CHK2 is a multiorgan tumor susceptibility gene that encodes for a serine/threonine protein kinase involved in the response to cellular DNA damage. After ATM-mediated phosphorylation, the activated Chk2 kinase can act as a signal transducer and phosphorylate a variety of substrates, including the Cdc25 phosphatases, p53, PML, E2F-1, and Brca1, which has been associated with halting the cell cycle, the initiation of DNA repair, and the induction of apoptosis after DNA damage. In addition, recent work has revealed another, DNA-damage–independent function of Chk2 during mitosis that is required for proper mitotic spindle assembly and maintenance of chromosomal stability. This novel role involves a mitotic phosphorylation of the tumor suppressor Brca1 by the Chk2 kinase. On the basis of its role during DNA damage response, Chk2 has been suggested as an anticancer therapy target, but given its recently discovered new function and its role as a tumor suppressor, it is questionable whether inhibition of Chk2 is indeed beneficial for anticancer treatment. However, investigators may be able to exploit the loss of CHK2 in human tumors to develop novel therapies based on synthetic lethal interactions. Clin Cancer Res; 17(3); 401–5. ©2010 AACR.
Partition of the Carotid Sinus Baroreceptor Response in Dogs between the Mechanical Properties of the Wall and the Receptor Elements
Authors: ESMAIL KOUSHANPOUR, DAVID M. KELSO
Journal: Circulation Research (1972)

The purpose of this investigation was to learn what part of the carotid sinus baroreceptor response is attributable to the gross mechanical properties of the wall and what part to the receptor elements. Static pressure forcings were applied to an isolated dog carotid sinus preparation while baroreceptor nerve activity was recorded; carotid sinus deformation was measured from still photographs taken during the experiment. Pressure-nerve activity data were obtained from four dogs and pressure-deformation data from another five dogs. The average electrical power in the nerve signal was used as the measure of nerve activity, and strain-energy density, a scalar quantity, was selected as the best indicator of the mechanical state of the sinus wall. Strain-energy density was calculated by measuring the circumferential and the longitudinal strains and by estimating the corresponding stresses in accordance with a thin-walled, axially symmetric model. The pressure-nerve activity data followed an S-shaped pattern, but the pressure-strain-energy density data were linear over the pressure range of 50 to 250 mm Hg. A curve of strain-energy density vs. nerve activity constructed from these two graphs, with pressure as the parametric variable, showed a linear relationship between nerve activity and strain-energy density over the pressure range of 75 to 175 mm Hg, but the slope of the curve rapidly went to zero with increasing pressure. We concluded that the nonlinearity in the pressure-nerve activity relationship was primarily due to the inability of the receptor elements to respond to increasing wall strains.
A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries
Authors: Sheila Fisher, Andrew Barry, Justin Abreu, Brian Minie, Jillian Nolan, Toni M Delorey, Geneva Young, Timothy J Fennell, Alexander Allen, Lauren Ambrogio, Aaron M Berlin, Brendan Blumenstiel, Kristian Cibulskis, Dennis Friedrich, Ryan Johnson, Frank Juhn, Brian Reilly, Ramy Shammas, John Stalker, Sean M Sykes, Jon Thompson, John Walsh, Andrew Zimmer, Zac Zwirko, Stacey Gabriel, Robert Nicol, Chad Nusbaum
Journal: Genome biology (2011)

Abstract Genome targeting methods enable cost-effective capture of specific subsets of the genome for sequencing. We present here an automated, highly scalable method for carrying out the Solution Hybrid Selection capture approach that provides a dramatic increase in scale and throughput of sequence-ready libraries produced. Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol.
Demonstration of altered fibroblast contractile activity in hypertensive heart disease
Authors: William A Marganski, Vanessa M De Biase, Maria L Burgess, Micah Dembo
Journal: Cardiovascular Research (2003)

Objective: The aim of this study is to investigate the idea that altered fibroblast contractile activity is involved in the pathogenesis of hypertensive heart disease (HHD). Methods: Cell area and contraction are quantified using the traction force microscopy technique for cardiac fibroblasts isolated from both normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Results: The data indicate that there are marked phenotypic differences between the two cell types. For instance, WKY fibroblasts exert an average traction stress of ∼3.3 kPa and have an area of ∼2640 μm2. Under identical conditions the SHR fibroblasts have an area ∼1.45 times larger (p<0.01) and exert an average stress ∼1.86 times higher (p<0.01). Challenging WKY fibroblasts with 1 μmol/l angiotensin II (Ang II) gradually causes a ∼2-fold increase in traction after 1 h while simultaneously causing a ∼28% decrease in area. In contrast, Ang II has no effect on SHR fibroblasts. The data also show that WKY and SHR cells respond in different ways when challenged with irbesartan (Irb). The addition of 1 μmol/l Irb initially causes WKY cells to decrease their average traction output by ∼50% after ∼10 min. Subsequently, contractile activity begins to recover and returns to normal after 1 h. The SHR cells also decrease their tractions by ∼50%, but this decrease requires 30 min for completion and there is no recovery to the initial contractile state. For both cell types, Irb produces no significant effect on area and the combined effect of equimolar Irb and Ang II is the same as Irb alone. Conclusion: These in vitro data suggest that among the many factors producing hypertensive heart disease in SHR's are excessive contraction of their cardiac fibroblasts and defective control of fibroblast contraction by Ang II.
Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma
Authors: Jie-Yi Shi, Qiang Gao, Zhi-Chao Wang, Jian Zhou, Xiao-Ying Wang, Zhi-Hui Min, Ying-Hong Shi, Guo-Ming Shi, Zhen-Bin Ding, Ai-Wu Ke, Zhi Dai, Shuang-Jian Qiu, Kang Song, Jia Fan
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The role of infiltrating B cells in hepatocellular carcinoma has been overlooked for many years. This study is aimed to delineate the distribution, prognostic value, and functional status of B cells in human hepatocellular carcinoma. Experimental design: Immunohistochemistry was used to investigate the distribution and clinical significance of infiltrating CD20+ B cells in a series of 120 patients with hepatocellular carcinoma. The results were further tested in an independent series of 200 patients with hepatocellular carcinoma. The functional status of CD20+ B cells was determined by flow cytometry, immunofluorescence, and in vitro coculture assay. Results: Infiltrating CD20+ B cells were predominantly concentrated in the tumor invasive margin, compared with the peri- and intratumor areas. High density of margin-infiltrating B lymphocytes (MIL-B) positively correlated with small tumor size, absence of vascular invasion, and increased density of CD8+ T cells (P &amp;lt; 0.05). Survival analyses revealed that increased number of MIL-Bs and their penetration through the tumor capsule were significantly associated with improved overall and recurrence-free survival, and were identified as independent prognosticators for patients with hepatocellular carcinoma (P &amp;lt; 0.05). Importantly, the results were further validated in another independent hepatocellular carcinoma cohort. Moreover, we found that MIL-Bs featured an atypical memory phenotype (IgD−IgG+CD27−CD38−), expressed surface markers characteristic of antigen-presenting cells, possessed tumor-killing potential by producing IFN-γ, interleukin 12p40 (IL-12p40), granzyme B, and TRAIL, and acted in cooperation with CD8+ T cells. Conclusions: The profile of CD20+ B cells in situ is a new predictor of prognosis for patients with hepatocellular carcinoma and provides a novel target for an optimal immunotherapy against this fatal malignancy. Clin Cancer Res; 19(21); 5994–6005. ©2013 AACR.
Estrogen Receptors α and β Are Inhibitory Modifiers of <i>Apc</i>-Dependent Tumorigenesis in the Proximal Colon of Min/+ Mice
Authors: Nancy L. Cho, Sara H. Javid, Adelaide M. Carothers, Mark Redston, Monica M. Bertagnolli
Journal: Cancer Research (2007)

Abstract Estrogen replacement therapy in postmenopausal women is associated with a reduction in colorectal cancer risk, potentially via interactions between 17β-estradiol (E2) and the estrogen receptors (ER) α and β. To study the role of E2 in intestinal tumor inhibition, we separately crossed C57BL/6J-Min/+ (Min/+) mice with Erα+/− and Erβ+/− mice to generate ER-deficient Min/+ progeny. We found an increased incidence of visible colon tumors and dysplastic microadenomas in ER-deficient Min/+ relative to Er+/+Min/+ controls. Small intestinal tumor numbers were unaffected. Invasive carcinomas were found only in Erα+/−Min/+ mice, suggesting that ERα plays additional non–cell autonomous roles that limit tumor progression. Histologic analyses of ER-deficient Min/+ colons, as well as colons from ovariectomized Min/+ mice (OvxMin/+) and E2-treated OvxMin/+ mice (OvxMin/+ +E2), revealed significant differences in crypt architecture, enterocyte proliferation, and goblet cell differentiation relative to Min/+ and Er+/+Apc+/+ (wild-type) controls. The expression of ERα and ERβ was regionally compartmentalized along the colonic crypt axis, suggesting functional antagonism. Our results indicate that ERα and ERβ are inhibitory modifiers of Apc-dependent colon tumorigenesis. As a result, loss of E2 and ER signaling in postmenopausal women may contribute to colorectal cancer development. [Cancer Res 2007;67(5):2366–72]
Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial
Authors: M Adjuik, P Agnamey, A Babiker, S Borrmann, P Brasseur, M Cisse, F Cobelens, S Diallo, JF Faucher, P Garner, S Gikunda, PG Kremsner, S Krishna, B Lell, M Loolpapit, P-B Matsiegui, MA Missinou, J Mwanza, F Ntoumi, P Olliaro, P Osimbo, P Rezbach, E Some, WRJ Taylor
Journal: The Lancet (2002)
Recurrent pneumothoraces in a 17-year-old man with mixed connective tissue disease
Authors: Claire McBrien, Andrea Penketh, Hilary Johnson, Andrew G Nicholson, Athol Wells
Journal: Thorax (2014)

CM : A 17-year-old man presented to the Emergency Department with chest tightness, cough and left-sided chest pain. He had been diagnosed with mixed connective disease as a child, having had Raynaud's syndrome associated with a positive antinuclear antibody with a speckled pattern and a positive ribonucleoprotein (RNP) antibody. He had never experienced respiratory symptoms or exercise limitation before. He had never smoked tobacco or cannabis, or been exposed to industrial dusts or chemicals. A chest radiograph revealed a spontaneous left-sided pneumothorax. A chest drain was inserted, with rapid resolution of the pneumothorax. Eleven days later, he developed a spontaneous right-sided pneumothorax, which failed to resolve with a 12Ch seldinger drain. A CT scan of the chest was performed (figure 1).



Figure 1 
CT chest, December 2011.



AP : The CT chest shows a large residual pneumothorax with mediastinal shift, drain in situ, and extensive, mainly subpleural, cystic change in both lungs, upper and lower lobes. This suggests advanced emphysema. I see that the α-1 anti-trypsin level is normal, therefore a lung biopsy should be obtained to further characterise his disease and search for a cause.

CM : The patient underwent a right video-assisted thoracoscopic surgery (VATS) bullectomy and pleurectomy, with wedge lung biopsy. Three days after discharge, he …
Genome-Wide Methylation Study Identifies an IL-13–induced Epigenetic Signature in Asthmatic Airways
Authors: Jessie Nicodemus-Johnson, Katherine A. Naughton, Jyotsna Sudi, Kyle Hogarth, Edward T. Naurekas, Dan L. Nicolae, Anne I. Sperling, Julian Solway, Steven R. White, Carole Ober
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Epigenetic changes to airway cells have been proposed as important modulators of the effects of environmental exposures on airway diseases, yet no study to date has shown epigenetic responses to exposures in the airway that correlate with disease state. The type 2 cytokine IL-13 is a key mediator of allergic airway diseases, such as asthma, and is up-regulated in response to many asthma-promoting exposures.To directly study the epigenetic response of airway epithelial cells (AECs) to IL-13 and test whether IL-13-induced epigenetic changes differ between individuals with and without asthma.Genome-wide DNA methylation and gene expression patterns were studied in 58 IL-13-treated and untreated primary AEC cultures and validated in freshly isolated cells of subjects with and without asthma using the Illumina Human Methylation 450K and HumanHT-12 BeadChips. IL-13-mediated comethylation modules were identified and correlated with clinical phenotypes using weighted gene coexpression network analysis.IL-13 altered global DNA methylation patterns in cultured AECs and were significantly enriched near genes associated with asthma. Importantly, a significant proportion of this IL-13 epigenetic signature was validated in freshly isolated AECs from subjects with asthma and clustered into two distinct modules, with module 1 correlated with asthma severity and lung function and module 2 with eosinophilia.These results suggest that a single exposure of IL-13 may selectively induce long-lasting DNA methylation changes in asthmatic airways that alter specific AEC pathways and contribute to asthma phenotypes.
Infections in the CNS During Childhood and the Risk of Subsequent Psychotic Illness: A Cohort Study of More Than One Million Swedish Subjects
Authors: Christina Dalman, Peter Allebeck, David Gunnell, Glyn Harrison, Krister Kristensson, Glyn Lewis, Sofia Lofving, Finn Rasmussen, Susanne Wicks, Håkan Karlsson
Journal: American Journal of Psychiatry (2007)

Infections during early life have been suggested to play a role in the etiology of schizophrenia. Most studies have focused on fetal life; few have explored risk associated with infection during childhood. The results of these have been inconsistent. The present study aims to investigate whether there is an increased risk of schizophrenia and other nonaffective psychoses associated with viral or bacterial CNS infections during childhood and, if so, which specific agents are involved.A national cohort consisting of 1.2 million children born between 1973 and 1985 was followed up by using Swedish national registers to retrieve data on hospital admissions for CNS infections at 0-12 years of age (bacterial: N=2,435, viral: N=6,550) as well as admissions for nonaffective psychotic illnesses from the 14th birthday (N=2,269).There was a slightly increased risk of nonaffective psychotic illness associated with viral CNS infections, as well as schizophrenia. There was no evidence of increased risk in relation to bacterial infections. When divided into specific agents, exposures to mumps virus or cytomegalovirus were associated with subsequent psychoses.Serious viral CNS infections during childhood appear to be associated with the later development of schizophrenia and nonaffective psychoses. The association with specific viruses suggests that the risk is related to infectious agents with a propensity to invade the brain parenchyma.