tbuckley/cabot-search huggingface dataset:
Endothelin receptor expression in idiopathic pulmonary arterial hypertension: effect of bosentan and epoprostenol treatment
Authors: S.M. Hall, N. Davie, N. Klein, S.G. Haworth
Journal: European Respiratory Journal (2011)

Endothelin receptor antagonists are used to treat idiopathic pulmonary arterial hypertension (IPAH), but human pulmonary arterial endothelin receptor expression is not well defined. We hypothesised that disease and treatment would modify normal receptor distribution in pulmonary resistance arteries of children. Using immunohistochemistry and semiquantitative analysis, we investigated endothelin receptor subtypes A and B (ET(A) and ET(B), respectively), and endothelial nitric oxide synthase (eNOS) expression in peripheral pulmonary arteries of tissue from untreated children with IPAH (n=7), following extended combined bosentan and epoprostenol therapy (n=5) and from normal subjects (n=5). Clinical, haemodynamic and pathological abnormalities were severe and advanced in all IPAH cases. ET(A) was detected in pulmonary arterial endothelial cells of all normal and diseased tissue and cultured cells. Endothelial ET(A), ET(B) and eNOS expression was reduced in patent, plexiform and dilatation lesions of untreated cases, but in treated cases, ET(A) and ET(B) were normal and eNOS increased. In smooth muscle, ET(A) expression was reduced in treated cases but ET(B) expression increased in all arteries of both treated and untreated cases. In summary, ET(A) is expressed on human pulmonary arterial endothelium. In IPAH, combination treatment with bosentan and epoprostenol had a more marked influence on endothelin receptor expression of endothelial than smooth muscle cells.
THE MEDICAL SERVICE, R.N
Authors: C. D. Marshall
Journal: BMJ (1914)

the Director-General of the Naval Medical Service, wlhich was givCn at Edinburglh, anld also the leadino article, both of whlich were published in the BRITISH MEDICAL JOUiRNAL of February 28tll, call attention to a very seriouLs condition of affairs in our first line of defence.In times past we lhave sometimes found tlhe navy the more popular service, and sometimes the army, according to the care and organization and pay of these two important branchies of State service.There is, as you point out, at the present
Enhanced detection of reversible perfusion defects by Tc-99m sestamibi compared to Tc-99m tetrofosmin during vasodilator stress SPECT imaging in mild-to-moderate coronary artery disease
Authors: Prem Soman, Raymond Taillefer, E.Gordon DePuey, James E Udelson, Avijit Lahiri
Journal: Journal of the American College of Cardiology (2001)
miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma
Authors: Shyamal D. Weeraratne, Vladimir Amani, Adrianne Neiss, Natalia Teider, Deborah K. Scott, Scott L. Pomeroy, Yoon-Jae Cho
Journal: Neuro-Oncology (2010)

Recent studies have established miR-34a as a key effector of the p53 signaling pathway and have implicated its role in multiple cancer types. Here, we establish that miR-34a induces apoptosis, G2 arrest, and senescence in medulloblastoma and renders these cells more sensitive to chemotherapeutic agents. These effects are mediated in part by the direct post-transcriptional repression of the oncogenic MAGE-A gene family. We demonstrate that miR-34a directly targets the 3' untranslated regions of MAGE-A genes and decreases MAGE-A protein levels. This decrease in MAGE-A results in a concomitant increase in p53 and its associated transcriptional targets, p21/WAF1/CIP1 and, importantly, miR-34a. This establishes a positive feedback mechanism where miR-34a is not only induced by p53 but increases p53 mRNA and protein levels through the modulation of MAGE-A genes. Additionally, the forced expression of miR-34a or the knockdown of MAGE-A genes by small interfering RNA similarly sensitizes medulloblastoma cells to several classes of chemotherapeutic agents, including mitomycin C and cisplatin. Finally, the analysis of mRNA and micro-RNA transcriptional profiles of a series of primary medulloblastomas identifies a subset of tumors with low miR-34a expression and correspondingly high MAGE-A expression, suggesting the coordinate regulation of these genes. Our work establishes a role for miR-34a in modulating responsiveness to chemotherapy in medulloblastoma and presents a novel positive feedback mechanism involving miR-34a and p53, via direct targeting of MAGE-A.
Outcome after resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia: Dutch nationwide retrospective cohort study
Authors: J K Kieboom, H J Verkade, J G Burgerhof, J J Bierens, P F van Rheenen, M C Kneyber, M J Albers
Journal: BMJ (2015)

<b>Objectives</b> To evaluate the outcome of drowned children with cardiac arrest and hypothermia, and to determine distinct criteria for termination of cardiopulmonary resuscitation in drowned children with hypothermia and absence of spontaneous circulation. <b>Design</b> Nationwide retrospective cohort study. <b>Setting</b> Emergency departments and paediatric intensive care units of the eight university medical centres in the Netherlands. <b>Participants</b> Children aged up to 16 with cardiac arrest and hypothermia after drowning, who presented at emergency departments and/or were admitted to intensive care. <b>Main outcome measure</b> Survival and neurological outcome one year after the drowning incident. Poor outcome was defined as death or survival in a vegetative state or with severe neurological disability (paediatric cerebral performance category (PCPC) ≥4). <b>Results</b> From 1993 to 2012, 160 children presented with cardiac arrest and hypothermia after drowning. In 98 (61%) of these children resuscitation was performed for more than 30 minutes (98/160, median duration 60 minutes), of whom 87 (89%) died (95% confidence interval 83% to 95%; 87/98). Eleven of the 98 children survived (11%, 5% to 17%), but all had a PCPC score ≥4. In the 62 (39%) children who did not require prolonged resuscitation, 17 (27%, 16% to 38%) survived with a PCPC score ≤3 after one year: 10 (6%) had a good neurological outcome (score 1), five (3%) had mild neurological disability (score 2), and two (1%) had moderate neurological disability (score 3). From the original 160 children, only 44 were alive at one year with any outcome. <b>Conclusions</b> Drowned children in whom return of spontaneous circulation is not achieved within 30 minutes of advanced life support have an extremely poor outcome. Good neurological outcome is more likely when spontaneous circulation returns within 30 minutes of advanced life support, especially when the drowning incident occurs in winter. These findings question the therapeutic value of resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia.
Alterations in human intestinal microflora during experimental diarrhoea
Authors: S. L. Gorbach, G. Neale, R. Levitan, G. W. Hepner
Journal: Gut (1970)

Large quantities of fluid administered through an intestinal tube caused alterations in small bowel bacteriology in four of seven subjects. In two normal individuals, colonic bacteria were found after fluid infusion in areas of the small bowel which previously had none. The faecal microflora was also altered by the fluid purge: anaerobes were reduced in some subjects and large numbers of <i>Enterobacter</i> species emerged in others. In a patient with pancreatic insufficiency and diarrhoea, the concentration of <i>Enterobacter</i> in the faeces was directly related to the number of bowel motions per day. Treatment with pancreatic enzymes curtailed the diarrhoea and markedly reduced these organisms. Intubation showed that <i>Enterobacter</i> were harboured in the small intestine and suppressed in the large bowel during periods of normal bowel action. Diarrhoea caused by pancreatic enzyme withdrawal or fluid purgation removed the colonic inhibition and allowed these organisms to appear in the faeces. Acidic diarrhoea induced by lactose feeding to three hypolactasic patients caused reductions in the numbers of <i>E. coli</i> in the stool but increases in <i>Enterobacter</i> species. Bacteroides also declined in one subject. Certain alterations in small and large bowel bacteriology observed in these forms of experimental diarrhoea have also been described in naturally occurring diarrhoea of diverse aetiologies.
Genetics of Cardiovascular Diseases
Authors: François Cambien, Laurence Tiret
Journal: Circulation (2007)

W hen the search for genes that predispose to cardiovas- cular diseases (CVD) started Ͼ20 years ago, it was anticipated that genetic polymorphisms might be analogous to the already known CVD risk factors and could be incorporated in a risk model such as the Framingham score 1 to assess the risk of an individual and adopt preventive or therapeutic measures accordingly.However, despite years of intensive research, not a single genetic risk factor is used for risk assessment.The new strategy of genome-wide association (GWA) studies (for example, see http://www.wtccc.org.uk/) coupled with the availability of very large cohorts of patients 2 is starting to reveal novel genetic factors that contribute to disease risk.Whether these variants will be clinically more useful than those that were derived from the study of candidate genes still needs to be demonstrated.As time passes, the interest for genetic research on common CVD moves progressively from the direct expectation of risk stratification to the more fundamental understanding of disease origins and pathophysiology and their indirect diagnostic and therapeutic implications.The objective of the present review is not to provide an exhaustive account of the numerous studies conducted on the genetics of CVD (eg, Arnett et al 3 ), but to introduce a few basic notions required to understand the language of genetics and genomics (see Appendix) and illustrate with a limited number of examples the important insights provided by genetic research into the causes and mechanisms of CVD.We will also discuss the new GWA strategy and why this approach is likely to have a considerable impact on biomedicine and human disease understanding.Finally, we will try to explain the unsuccessful search for genetic markers of risk and why phenotypic biomarkers are likely to be clinically more useful.
GLP-1 Responses Are Heritable and Blunted in Acquired Obesity With High Liver Fat and Insulin Resistance
Authors: Niina Matikainen, Leonie H. Bogl, Antti Hakkarainen, Jesper Lundbom, Nina Lundbom, Jaakko Kaprio, Aila Rissanen, Jens J. Holst, Kirsi H. Pietiläinen
Journal: Diabetes Care (2013)

OBJECTIVE Impaired incretin response represents an early and uniform defect in type 2 diabetes, but the contributions of genes and the environment are poorly characterized. RESEARCH DESIGN AND METHODS We studied 35 monozygotic (MZ) and 75 dizygotic (DZ) twin pairs (discordant and concordant for obesity) to determine the heritability of glucagon-like peptide 1 (GLP-1) responses to an oral glucose tolerance test (OGTT) and the influence of acquired obesity to GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) during OGTT or meal test. RESULTS The heritability of GLP-1 area under the curve was 67% (95% CI 45–80). Cotwins from weight-concordant MZ and DZ pairs and weight-discordant MZ pairs but concordant for liver fat content demonstrated similar glucose, insulin, and incretin profiles after the OGTT and meal tests. In contrast, higher insulin responses and blunted 60-min GLP-1 responses during the OGTT were observed in the heavier as compared with leaner MZ cotwins discordant for BMI, liver fat, and insulin sensitivity. Blunted GLP-1 response to OGTT was observed in heavier as compared with leaner DZ cotwins discordant for obesity and insulin sensitivity. CONCLUSIONS Whereas the GLP-1 response to the OGTT is heritable, an acquired unhealthy pattern of obesity characterized by liver fat accumulation and insulin resistance is closely related to impaired GLP-1 response in young adults.
Hepatocellular disease in the giant-cell arteritis/polymyalgia rheumatica syndrome.
Authors: A S Leong, M H Alp
Journal: Annals of the Rheumatic Diseases (1981)

An elderly man developed temporal arteritis and polymyalgia rheumatica with coexisting biochemical abnormalities of liver function. Biopsy revealed hepatic changes which have not been previously reported. There was hepatocellular necrosis and inflammation together with a prominent hyperplasia of perisinusoidal lipocytes of Ito. Temporal artery biopsy confirmed the presence of granulomatous panarteritis. Corticosteroid therapy produced rapid resolution of symptoms and reversion of liver function tests to normal.
Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data
Authors: Blanka Ríhová, Jirí Strohalm, Jana Prausová, Katerina Kubácková, Markéta Jelínková, Lad'ka Rozprimová, Milada Sírová, Dana Plocová, Tomás Etrych, Vladimír Subr, Tomás Mrkvan, Marek Kovár, Karel Ulbrich
Journal: Journal of Controlled Release (2003)
H-2D control of recovery from Friend virus leukemia: H-2D region influences the kinetics of the T lymphocyte response to Friend virus.
Authors: W J Britt, B Chesebro
Journal: The Journal of Experimental Medicine (1983)

A Friend virus (FV)-specific T lymphocyte proliferation assay was used to compare the T lymphocyte responses of H-2 congenic mice that differed in their ability to recover from FV leukemia after inoculation of high virus doses. Gene(s) of the H-2D region influenced the kinetics of this response such that H-2Db/b homozygous mice were positive 6-8 d earlier than H-2Dd/b mice. This correlated with the Rfv-1, H-2D-linked influence on recovery from FV by these mice, and also appeared to explain the prominent effect of virus dose on recovery incidence. These findings were supported by the ability of passively transferred immune splenic T lymphocytes to induce recovery from leukemia at 6 d after FV inoculation, but not at 16 d. H-2a/a mice were found to be unresponsive in the FV-specific T lymphocyte proliferation assay. This effect mapped to the left of H-2D, possibly in the H-2I region, and may be an in vitro manifestation of the Rfv-2 gene. No evidence for nonspecific immunosuppression of the T lymphocyte response to concanavalin A was observed in any of the H-2 congenic F1 mice studied.
An Analysis of G-U Base Pair Occurrence in Eukaryotic 5S rRNAs
Authors: Maciej Szyma, Mirosława Z. Barciszewska, Volker A. Erdmann, Jan Barciszewski
Journal: Molecular Biology and Evolution (2000)

The structure-function relationship in RNA molecules is a key to understanding of the expression of genetic information. Various types of RNA play crucial roles at almost every step of protein biosynthesis. In recent years, it has been shown that one of the most important structural elements in RNA is a wobble pair G-U. In this paper, we present for the first time an analysis of the distribution of G-U pairs in eukaryotic 5S ribosomal RNAs. Interestingly, the G-U pair in 5S rRNA species is predominantly found in two intrahelical regions of the stems I and V and at the junction of helix IV and loop A. The distribution of G-U pairs and the nature of adjacent bases suggests their possible role as a recognition site in interactions with other components of protein biosynthesis machinery.
Lung function in adult idiopathic scoliosis: a 20 year follow up.
Authors: K Pehrsson, B Bake, S Larsson, A Nachemson
Journal: Thorax (1991)

Severe idiopathic scoliosis may lead to respiratory failure, which can be treated by assisted ventilation. Twenty four patients with surgically untreated idiopathic scoliosis who had been examined in 1968 were re-examined in 1988 to assess changes in lung function and risk factors for respiratory failure. The patients were aged 15-67 years in 1968 and had a scoliotic angle of 10-190 degrees and a vital capacity of 1.0-6.0 litres. Spirometric values and scoliotic angles were determined in 1968 and 1988, and arterial blood gas tensions in 1988. The decline in spirometric values over the 20 years was of the same magnitude as the predicted decline due to aging. Arterial blood gas tensions in 1988 were strongly correlated with the scoliotic angles and spirometric indices recorded in 1968. Hypoxaemia and hypercapnia was seen in four patients in 1988 (then aged 43-67 years) and these were the four patients who had a vital capacity below 43% predicted in 1968. The remaining 20 patients had blood gas values within normal limits. Two further patients had died from respiratory failure before 1988, so a total of six patients had developed respiratory failure. In a multiple logistic analysis vital capacity expressed as % predicted in 1968 was the strongest predictor of the development of respiratory failure, followed by the scoliotic angle. Respiratory failure occurred only in patients who had a vital capacity below 45% predicted in 1968 and an angle greater than 110 degrees. Thus respiratory failure develops in adults with scoliosis with a large angle and a low vital capacity when normal aging reduces the ventilatory capacity further. Such individuals merit close follow up.
Green Tea Polyphenols Reverse Cooperation between c-Rel and CK2 that Induces the Aryl Hydrocarbon Receptor, Slug, and an Invasive Phenotype
Authors: Karine Belguise, Shangqin Guo, Shi Yang, Adrianne E. Rogers, David C. Seldin, David H. Sherr, Gail E. Sonenshein
Journal: Cancer Research (2007)

Abstract Exposure to and bioaccumulation of lipophilic environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs), has been implicated in breast cancer. Treatment of female rats with the prototypic xenobiotic PAH 7,12-dimethylbenz(a)anthracene (DMBA) induces mammary tumors with an invasive phenotype. Here, we show that green tea prevents or reverses loss of the epithelial marker E-cadherin on the surface of DMBA-induced in situ cancers. To investigate the mechanism(s) leading to a less invasive phenotype, the effects of the green tea polyphenol epigallocatechin-3 gallate (EGCG) on mammary tumor cells were assessed. EGCG reversed epithelial to mesenchymal transition (EMT) in DMBA-treated NF-κB c-Rel–driven mammary tumor cells and reduced levels of c-Rel and the protein kinase CK2. Ectopic coexpression of c-Rel and CK2α in untransformed mammary epithelial cells was sufficient to induce a mesenchymal gene profile. Mammary tumors and cell lines derived from MMTV-c-Rel × CK2α bitransgenic mice displayed a highly invasive phenotype. Coexpression of c-Rel and CK2, or DMBA exposure induced the aryl hydrocarbon receptor (AhR) and putative target gene product Slug, an EMT master regulator, which could be reversed by EGCG treatment. Thus, activation of c-Rel and CK2 and downstream targets AhR and Slug by DMBA induces EMT; EGCG can inhibit this signaling. [Cancer Res 2007;67(24):11742–50]
Watchdog warns over future use of private finance initiative
Authors: A. O'Dowd
Journal: BMJ (2011)

The national spending watchdog has issued a warning over future use of any private finance initiatives to build hospitals, saying other ways of funding public projects might be better value for money.

The National Audit Office (NAO) says, in a report published on 28 April, that there has been no thorough value for money evaluations of existing private finance initiative (PFI) projects by government departments, so future projects have to be approached with caution.

Currently 698 PFI projects have been signed in the UK with a combined capital value of £52.9bn (€59.4bn; $87.3bn). Such projects include agreements in which private companies build hospitals and NHS …
Liberalism, chauvinism, and experimental thought
Authors: C. M. Heyes
Journal: Behavioral and Brain Sciences (1998)

The target article argued that there is currently no reliable evidence of theory of mind in nonhuman primates and proposed research methods for future use in this field. Some commentators judged the research proposals to be too chauvinist (in danger of falsely denying that primates attribute mental states), but a majority judged them to be too liberal (in danger of falsely affirming theory of mind in primates). The most valuable comments from both camps exemplified “experimental thought,” the obverse of “thought experiments,” and recommended specific alterations and alternatives to the studies I proposed. This Response evaluates these recommendations and presents a revised version of the proposals that appear in the target article. Other valuable commentary cast doubt on the assumption that people have a theory of mind, aired the possibility that language may be a prerequisite for either possession or detection of a theory of mind, questioned the notion of critical experiments, and emphasized the distinction between attribution of sight and belief. In addition to commenting on these issues, I respond to objections to my interpretation of existing research on self-recognition, imitation, and deception.
Airway macrophage phagocytosis after high altitude residence in children with asthma
Authors: Neeta Kulkarni, Vincenzo Ragazzo, Silvia Costella, Ahmad Kantar, Christopher O'Callaghan
Journal: European Respiratory Journal (2012)

Airway macrophages (AM) perform crucial function of clearing pathogens and presenting antigens. AM phagocytosis in adults with mild asthma is enhanced compared to healthy individuals and possibly related to higher level of activation of macrophages1. At high altitude there is reduced exposure to allergens. However it is not known what effect this has on the macrophage phagocytosis.

The aim was to determine the phagocytic function of airway macrophages at baseline (T0) and after stay at high altitude (T1).

Sputum induction was performed at T0 and T1 in children with mild to moderate asthma attending High Altitude Children's Asthma Center in Misurina. Differential count was obtained by counting 400 non-squamous cells (eosinophilic asthma ≥ 3%). AM were isolated by adherence and cultured with FITC labelled heat killed staph aureus in the ratio of 1:10 (AM: bacteria). One hundred macrophages were imaged using confocal microscope. The median bacterial count/AM was calculated using Image J and Cell profiler software. The groups were compared using paired and unpaired t-tests.

There was no significant difference (p = 0.3) between median bacterial count in eosinophilic (n=16) \[Mean (SD)\] \[77.56(36.6)\] and non-eosinophilic asthma (n=8) \[68.22(11.5)] at T0. Children at T1 (n=19 pairs) had significantly lower i) median bacterial count [Mean (SD)\] \[p = 0.006, 39.55(4.51) vs 73.26 (39.42)\] than at T0.

The sputum macrophages in children with mild to moderate asthma are equally phagocytic in eosinophilic or non-eosinophilic groups. After stay at high altitude macrophages were less phagocytic (possibly due to return to normal level of activation).

1Lay JC et al Thorax 2009; 64:313–320.