tbuckley/cabot-search huggingface dataset:
MPs question potential new chair of Monitor about his work for company advising private health firms
Authors: A. O'Dowd
Journal: BMJ (2013)

The potential new head of Monitor, which regulates competition in the NHS, has defended his previous role working for a consultancy advising private health companies on how to exploit opportunities in the NHS in an evidence session held before MPs. 

Dominic Dodd appeared before MPs on the parliamentary health select committee on 15 October as part of a pre-appointment hearing. Dodd is the government’s preferred candidate for the post.

MPs asked him about his time working with management consultancy firm Marakon Associates, which works in healthcare. One MP quoted the firm’s website as saying, “Now more than ever, there is an opportunity for healthcare companies to exploit the new market environment and private health firms have the opportunity to capture and retain new consumers.” 

Dodd said that he had spent time in the private sector in a …
SUBLEUKAEMIC LYMPHADENOSIS IN A CHILD
Authors: G. S. Smith
Journal: BMJ (1934)

Of the recorded cases some deaths occurred at a very early age, while others have been known to reach the age of 21 (Calandre4), 20 (Smith5), and 18 (Myer6) years.Dr. Aitken,7 in her excellent survey of the literature, described two cases of this abnormality, and suggests an overgrowth of fibrous tissue between the auricle and ventricle as the possible cause, leading to interference with the conduction through the bundle of His.
Viral infection and the pathogenesis of dilated cardiomyopathy.
Authors: T A Martino, P Liu, M J Sole
Journal: Circulation Research (1994)

Long-term follow-up studies of patients with suspected viral myocarditis reveal progression to dilated cardiomyopathy (DCM) in a significant number of cases. Thus, an underlying viral etiology has been hypothesized in the pathogenesis of ongoing heart disease that leads to DCM. Recent application of molecular biology in clinical diagnosis has strengthened this hypothesis. By use of probe hybridization and polymerase chain reaction, enteroviral RNA has been detected in the myocardium of patients at all stages of the disease process: myocarditis, chronic heart disease, and DCM. Experimental murine models of enterovirus-induced heart disease provide a framework for examining the pathogenic mechanisms. Viral cytotoxicity, immunological responses, viral RNA persistence, and spasm of the coronary microvasculature are all implicated in the ongoing disease process. Abnormal cardiac function and heart failure are attributed to the pathological changes that occur.
Gas cooking is associated with small reductions in lung function in children
Authors: H. Moshammer, T. Fletcher, J. Heinrich, G. Hoek, F. Hruba, S. Pattenden, P. Rudnai, H. Slachtova, F. E. Speizer, R. Zlotkowska, M. Neuberger
Journal: European Respiratory Journal (2009)

Inconsistent effects of gas cooking on lung function have been reported. In a previous study from Austria, we demonstrated a significant, though small, reduction of lung function parameters in children living in homes with gas stoves. We used a larger international database to check if this finding can be generalised. To study the relative impact of cooking with gas on lung function parameters of primary school children in a wide range of geographical settings, we analysed flow and volume data of approximately 24,000 children (aged 6-12 yrs) from nine countries in Europe and North America. Exposure information was obtained by comparable questionnaires and spirometry according to an American Thoracic Society/European Respiratory Society protocol. Linear regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytical tools. On average, gas cooking reduced lung function parameters. Overall effects were small (-0.1-0.7%) and only significant for forced vital capacity and forced expiratory volume in 1 s. There was some indication that allergic children were more affected by gas cooking. Under current housing conditions, gas cooking is associated with only small reductions in lung function.
Fusion-Derived Epithelial Cancer Cells Express Hematopoietic Markers and Contribute to Stem Cell and Migratory Phenotype in Ovarian Carcinoma
Authors: Mallika Ramakrishnan, Sandeep R. Mathur, Asok Mukhopadhyay
Journal: Cancer Research (2013)

For a long time, the external milieu of cancer cells was considered to be of secondary importance when compared with its intrinsic properties. That has changed now as the microenvironment is considered to be a major contributing factor toward the progression of tumor. In this study, we show that in human and mouse epithelial ovarian carcinoma and mouse lung carcinoma, the interaction between tumor-infiltrating hematopoietic cells and epithelial cancer cells results in their fusion. Intriguingly, even after the fusion event, cancer cells retain the expression of the pan-hematopoietic marker (CD45) and various markers of hematopoietic lineage, including those of hematopoietic stem cells, indicating that the hematopoietic genome is not completely reprogrammed. This observation may have implications on the bone marrow contribution to the cancer stem cell population. Interestingly, it was seen that in both cancer models, the expression of chemokine receptor CXCR4 was largely contributed to by the fused compartment of cancer cells. We hypothesize that the superior migratory potential gained by the cancer cells due to the fusion helps in its dissemination to various secondary organs upon activation of the CXCR4/CXCL12 axis. We are the first to report the presence of a hemato-epithelial cancer compartment, which contributes to stem cell markers and CXCR4 in epithelial carcinoma. This finding has repercussions on CXCR4-based therapeutics and opens new avenues in discovering novel molecular targets against fusion and metastasis.
Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type II
Authors: Lin Wang, Huiping Dong, Carol J. Soroka, Ning Wei, James L. Boyer, Mark Hochstrasser
Journal: Hepatology (2008)

The bile salt export pump (Bsep) represents the major bile salt transport system at the canalicular membrane of hepatocytes. When examined in model cell lines, genetic mutations in the BSEP gene impair its targeting and transport function, contributing to the pathogenesis of progressive familial intrahepatic cholestasis type II (PFIC II). PFIC II mutations are known to lead to a deficiency of BSEP in human hepatocytes, suggesting that PFIC II mutants are unstable and degraded in the cell. To investigate this further, we have characterized the impact of several PFIC II mutations on the processing and stability of rat Bsep. G238V, D482G, G982R, R1153C, and R1286Q all retain Bsep to the endoplasmic reticulum (ER) to different extents. Except for R1153C, the PFIC II mutants are degraded with varying half-lives. G238V and D482G are partially misfolded and can be stabilized by low temperature and glycerol. The proteasome provides the major degradation pathway for the PFIC II mutants, whereas the lysosome also contributes to the degradation of D482G. The PFIC II mutants appear to be more heavily ubiquitinated compared with the wild-type (wt) Bsep, and their ubiquitination is increased by the proteasome inhibitors. Overexpression of several E3 ubiquitin ligases, which are involved in ER-associated degradation (ERAD), lead to the decrease of both mutant and wt Bsep. Gene knockdown studies showed that the ERAD E3s Rma1 and TEB4 contribute to the degradation of G238V, whereas HRD1 contributes to the degradation of a mutant lacking the lumenal glycosylation domain (DeltaGly). Furthermore, we present evidence that G982R weakly associates with various components of the ER quality control system. These data together demonstrate that the PFIC II mutants except R1153C and DeltaGly are degraded by the ERAD pathway.
Quantification of global transcription patterns in prokaryotes using spotted microarrays
Authors: Ben Sidders, Mike Withers, Sharon L Kendall, Joanna Bacon, Simon J Waddell, Jason Hinds, Paul Golby, Farahnaz Movahedzadeh, Robert A Cox, Rosangela Frita, Annemieke MC ten Bokum, Lorenz Wernisch, Neil G Stoker
Journal: Genome biology (2007)

We describe an analysis, applicable to any spotted microarray dataset produced using genomic DNA as a reference, that quantifies prokaryotic levels of mRNA on a genome-wide scale. Applying this to Mycobacterium tuberculosis, we validate the technique, show a correlation between level of expression and biological importance, define the complement of invariant genes and analyze absolute levels of expression by functional class to develop ways of understanding an organism's biology without comparison to another growth condition.
The Predictive Value of HLA Class I Tumor Cell Expression and Presence of Intratumoral Tregs for Chemotherapy in Patients with Early Breast Cancer
Authors: Esther M. de Kruijf, Johanna G.H. van Nes, Anita Sajet, Quirijn R.J.G. Tummers, Hein Putter, Susanne Osanto, Frank M. Speetjens, Vincent T.H.B.M. Smit, Gerrit Jan Liefers, Cornelis J.H. van de Velde, Peter J.K. Kuppen
Journal: Clinical Cancer Research (2010)

We hypothesized that T-cell immune interaction affects tumor development and thus clinical outcome. Therefore, we examined the clinical impact of human leukocyte antigen (HLA) class I tumor cell expression and regulatory T-cell (Treg) infiltration in breast cancer.Our study population (N = 677) is consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Formalin-fixed, paraffin-embedded tumor tissue was immunohistochemically stained using HCA2, HC10, and Foxp3 monoclonal antibodies.HLA class I expression was evaluated by combining results from HCA2 and HC10 antibodies and classified into three groups: loss, downregulation, and expression. Remarkably, only in patients who received chemotherapy, both presence of Treg (P = 0.013) and higher HLA class I expression levels (P = 0.002) resulted in less relapses, independently of other variables. Treg and HLA class I were not of influence on clinical outcome in patients who did not receive chemotherapy.We showed that HLA class I and Treg affect prognosis exclusively in chemotherapy-treated patients and are therefore one of the few predictive factors for chemotherapy response in early breast cancer patients. Chemotherapy may selectively eliminate Treg, thus enabling CTLs to kill tumor cells that have retained HLA class I expression. As a consequence, HLA class I and Treg can predict response to chemotherapy with high discriminative power. These markers could be applied in response prediction to chemotherapy in breast cancer patients.
Scavenger receptor BI and ABCG5/G8 differentially impact biliary sterol secretion and reverse cholesterol transport in mice
Authors: Arne Dikkers, Jan Freak de Boer, Wijtske Annema, Albert K. Groen, Uwe J.F. Tietge
Journal: Hepatology (2013)

Abstract Biliary lipid secretion plays an important role in gallstone disease and reverse cholesterol transport (RCT). Using Sr-bI/Abcg5 double knockout mice (dko), the present study investigated the differential contribution of two of the most relevant transporters: adenosine triphosphate (ATP)-binding cassette subfamily G member 5 and 8 (ABCG5/G8) and scavenger receptor class B type I (SR-BI) to sterol metabolism and RCT. Plasma cholesterol levels increased in the following order, mainly due to differences in high density lipoprotein (HDL): Abcg5 ko &lt; wild type &lt; Sr-bI/Abcg5 dko &lt; Sr-bI ko. Liver cholesterol content was elevated in Sr-bI ko only ( P &lt; 0.05). In Sr-bI/Abcg5 dko plasma plant sterols were highest, while hepatic plant sterols were lower compared with Abcg5 ko ( P &lt; 0.05). Under baseline conditions, biliary cholesterol secretion rates decreased in the following order: wild type &gt; Sr-bI ko (−16%) &gt; Abcg5 ko (−75%) &gt; Sr-bI/Abcg5 dko (−94%), all at least P &lt; 0.05, while biliary bile acid secretion did not differ between groups. However, under supraphysiological conditions, upon infusion with increasing amounts of the bile salt tauroursodeoxycholic acid, Abcg5 became fully rate-limiting for biliary cholesterol secretion. Additional in vivo macrophage-to-feces RCT studies demonstrated an almost 50% decrease in overall RCT in Sr-bI/Abcg5 dko compared with Abcg5 ko mice ( P &lt; 0.01). Conclusion : These data demonstrate that (1) SR-BI contributes to ABCG5/G8-independent biliary cholesterol secretion under basal conditions; (2) biliary cholesterol mass secretion under maximal bile salt-stimulated conditions is fully dependent on ABCG5/G8; and (3) Sr-bI contributes to macrophage-to-feces RCT independent of Abcg5/g8. (Hepatology 2013;)
Secular Trends in Diabetes-Related Preventable Hospitalizations in the United States, 1998–2006
Authors: Jing Wang, Kumiko Imai, Michael M. Engelgau, Linda S. Geiss, Christina Wen, Ping Zhang
Journal: Diabetes Care (2009)

OBJECTIVE To examine secular trends in diabetes-related preventable hospitalizations among adults with diabetes in the U.S. from 1998 to 2006. RESEARCH DESIGN AND METHODS We used nationally representative data from the National Inpatient Sample to identify diabetes-related preventable hospitalizations. Based on the Agency for Healthcare Research and Quality's Prevention Quality Indicators, we considered that hospitalizations associated with the following four conditions were preventable: uncontrolled diabetes, short-term complications, long-term complications, and lower-extremity amputations. Estimates of the number of adults with diabetes were obtained from the National Health Interview Survey. Rates of hospitalizations among adults with diabetes were derived and tested for trends. RESULTS Age-adjusted rates for overall diabetes-related preventable hospitalizations per 100 adults with diabetes declined 27%, from 5.2 to 3.8 during 1998–2006 (Ptrend &amp;lt; 0.01). This rate decreased significantly for all but not for short-term complication (58% for uncontrolled diabetes, 37% for lower-extremity amputations, 23% for long-term complications [all P &amp;lt; 0.01], and 15% for the short-term complication [P = 0.18]). Stratified by age-group and condition, the decline was significant for all age-condition groups (all P &amp;lt; 0.05) except short-term complications (P = 0.33) and long-term complications (P = 0.08) for the age-group 18–44 years. The decrease was significant for all sex-condition combination subgroups (all P &amp;lt; 0.01). CONCLUSIONS We found a decrease in diabetes-related preventable hospitalizations in the U.S. from 1998 to 2006. This trend could reflect improvements in quality of primary care for individuals with diabetes.
Divergent Expression Regulation of Gonad Development Genes in Medaka Shows Incomplete Conservation of the Downstream Regulatory Network of Vertebrate Sex Determination
Authors: Amaury Herpin, Mateus C. Adolfi, Barbara Nicol, Maria Hinzmann, Cornelia Schmidt, Johanna Klughammer, Mareen Engel, Minoru Tanaka, Yann Guiguen, Manfred Schartl
Journal: Molecular Biology and Evolution (2013)

Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.
Impact of Immunomodulating Therapy on Morbidity in Patients with Severe Sepsis
Authors: DIDIER PITTET, STEPHAN HARBARTH, PETER M. SUTER, KONRAD REINHART, ANTON LEIGHTON, CHRISTOPHER BARKER, FRANCES MACDONALD, EDWARD ABRAHAM
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We assessed the impact, over a 28-d period, of therapy with the tumor necrosis factor (TNF) neutralizing receptor fusion protein (p55-IgG) on the incidence of end-organ failures in patients with severe sepsis or early septic shock in a subgroup of 165 patients recruited into a randomized, multicenter clinical trial to receive placebo (n = 78) or a single infusion of p55-IgG, 0.083 mg/kg (n = 87). At study entry, distribution of organ dysfunctions and other baseline characteristics were similar for the two study groups. Treatment with p55-IgG was associated with a trend toward reduced 28-d mortality (p = 0.07), a decreased incidence of new organ dysfunctions (relative risk [RR], 0.57; 95% confidence interval [95% CI] 0.29 to 1.10, p = 0.10), and a decreased overall incidence-density of organ failures (RR 0.65; 95% CI 0.60 to 0.71, p = 0.0001). Patients treated with p55-IgG had more organ failure–free days after study entry than those who received placebo. Average intensive care unit (ICU) stay was 2.6 d shorter (95% CI 0.2 to 5.0) for patients who received p55-IgG than for those who received placebo. For those patients who survived, this difference was 4.1 d (95% CI 1.6 to 6.6). Duration of ventilatory support was 3.2 d shorter (95% CI 0.1 to 6.3) among 28-d survivors who received p55-IgG, compared with placebo. In conclusion, in the population of septic patients studied, treatment with p55-IgG was associated with a trend toward shorter need for mechanical ventilatory support, a decreased length of stay (LOS), and a decreased incidence and duration of organ failure.
Grist for the Mill: Role of Cereal Fiber and Calcium in Prevention of Colon Cancer
Authors: M. J. Wargovich, B. Levin
Journal: JNCI Journal of the National Cancer Institute (1996)

Investigation into the causes and prevention of colon cancer has always been a fascinating area of cancer research. It remains so because of the complex interplay of genetics and environment in the etiology of this common malignancy (7,2). The dietary milieu probably provides mutagens that initiate colon carcinogenesis, altering critical genes involved in its genesis, and is the source of substances that promote the tumorigenic process. Fortunately, as the epidemiologic evidence underscores, the diet is seemingly rich in factors that modulate risk for the disease (3-5). An impressive amount of experimental evidence, especially in laboratory animal studies, supports protective roles for cereal fiber and calcium in influencing risk for colon cancer. In carcinogen-treated rodents, research studies (6-13) have consistently implicated dietary fiber from wheat and supplemental dietary calcium as potentially protective in terms of reducing colon cell hyperproliferation upon short-term feeding and in reducing and protecting against the development of colon cancer in the longer term. The results have been inconsistent regarding the cancer preventive effects of other forms of cereal fiber. Some studies even suggested an adverse effect on the colon; i.e., some soluble forms of fiber have been shown to enhance cellular proliferation in the colon (14,15). From the human standpoint, relatively few studies have addressed the possible mechanism of action of added dietary fiber and calcium in the prevention of colon cancer. One hypothesis that has withstood the test of time suggests that the digestion of a diet rich in fat enhances the release of primary and secondary
House dust mite‐induced calcium signaling instigates epithelial barrier dysfunction and <scp>CCL</scp>20 production
Authors: S. Post, M. C. Nawijn, M. R. Jonker, N. Kliphuis, M. van den Berge, A. J. M. van Oosterhout, I. H. Heijink
Journal: Allergy (2013)

House dust mite (HDM) affects the immunological and physical barrier function of airway epithelium, leading to allergic sensitization, airway remodeling, and eosinophilic inflammation in mouse models, although the mechanisms are still largely unknown.Given the implications for adenosine triphosphate (ATP)-dependent Ca(2+) signaling in allergic sensitization in mice, we sought to determine the role of intracellular Ca(2+) concentration ([Ca(2+)](i)) in HDM-induced barrier dysfunction and pro-inflammatory activity of bronchial epithelium.We investigated the effect of HDM on accumulation of [Ca(2+)](i) levels, barrier function, and CCL20 release in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBECs) from healthy subjects and asthma patients. Involvement of ATP-dependent activation of purinergic receptors and downstream Ca(2+) influx was studied, using the ATP hydrolyzing agent apyrase, the purinergic receptor agonist PPADS, the calcium chelator BAPTA-AM, and calpain inhibitors.Asthma PBECs were more susceptible to HDM-induced barrier dysfunction, CCL20 secretion, and Ca(2+) influx than healthy PBECs. Furthermore, we show that the HDM-induced increase in CCL20 in PBECs and 16HBE cells and the HDM-induced barrier dysfunction in 16HBE cells are dependent on [Ca(2+)](i) accumulation. Additionally, we demonstrate that [Ca(2+)](i) accumulation is initiated partly through the activation of purinergic receptors, which contributes to HDM-induced epithelial barrier dysfunction by disruption of cell-cell contacts, but not CCL20 secretion.Our data show for the first time that Ca(2+) signaling plays a crucial role in barrier dysfunction and the pro-inflammatory response of bronchial epithelium upon HDM exposure and may thus have important implications for the development of allergic asthma.
High detection rate of human papillomavirus in anal brushings from women attending a proctology clinic
Authors: Alessandra Pierangeli, Carolina Scagnolari, Carla Selvaggi, Fabiana Cannella, Elisabetta Riva, Alessio Impagnatiello, Gloria Bernardi, Antonio Ciardi, Cosima Maria Moschella, Guido Antonelli, Marileda Indinnimeo
Journal: Journal of Infection (2012)