tbuckley/cabot-search huggingface dataset:
Diagnostic and prognostic value of serum antibodies against Pseudomonas aeruginosa in cystic fibrosis
Authors: M Kappler
Journal: Thorax (2006)

<b>Background:</b> Eradication of <i>Pseudomonas aeruginosa</i> in patients with cystic fibrosis (CF) is possible if initiated early in the course of colonisation. To detect <i>P aeruginosa</i> as early as possible is therefore a major goal. This study was undertaken to validate a commercialised test for the detection of serum <i>Pseudomonas</i> antibodies in patients with CF. <b>Methods:</b> A representative cross sectional analysis of serum antibodies against three <i>Pseudomonas</i> antigens (alkaline protease, elastase, and exotoxin A) was performed in 183 patients with CF of mean age 16.7 years and FEV<sub>1</sub> 85.9% predicted. The results were correlated with microbiological results from the previous 2 years to calculate sensitivity, specificity, positive and negative predictive values. The following 2 years were assessed to determine prognostic predictive values. <b>Results:</b> A combination of all three tested antibodies yielded the best results with a sensitivity of 86%, specificity of 96%, and a positive predictive value of 97%. These values were higher if only patients in whom sputum cultures were available were considered (n = 76, sensitivity 95%, specificity 100%, positive predictive value 100%). The prognostic positive predictive value was high in intermittently infected patients (83%) but low in patients free of infection (33%), whereas the prognostic negative predictive value was high in patients free of infection (78%) and low in intermittently infected patients (58%). <b>Conclusions:</b> Regular determination of serum antibodies may be useful in CF patients with negative or intermittent but not with positive <i>P aeruginosa</i> status. A rise in antibody titres indicates probable infection and eradication treatment may be initiated even in the absence of microbiological detection of <i>P aeruginosa</i>.
Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications
Authors: Pasquapina Ciarmela, Md. Soriful Islam, Fernando M. Reis, Peter C. Gray, Enrrico Bloise, Felice Petraglia, Wylie Vale, Mario Castellucci
Journal: Human Reproduction Update (2011)

Growth factors are proteins secreted by a number of cell types that are capable of modulating cellular growth, proliferation and cellular differentiation. It is well accepted that uterine cellular events such as proliferation and differentiation are regulated by sex steroids and their actions in target tissues are mediated by local production of growth factors acting through paracrine and/or autocrine mechanisms. Myometrial mass is ultimately modified in pregnancy as well as in tumour conditions such as leiomyoma and leiomyosarcoma. Leiomyomas, also known as fibroids, are benign tumours of the uterus, considered to be one of the most frequent causes of infertility in reproductive years in women.For this review, we searched the database MEDLINE and Google Scholar for articles with content related to growth factors acting on myometrium; the findings are hereby reviewed and discussed.Different growth factors such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), heparin-binding EGF (HB-EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and TGF-β perform actions in myometrium and in leiomyomas. In addition to these growth factors, activin and myostatin have been recently identified in myometrium and leiomyoma.Growth factors play an important role in the mechanisms involved in myometrial patho-physiology.
Quality control of DL,CO instruments in global clinical trials
Authors: R. Jensen, M. Leyk, R. Crapo, D. Muchmore, P. Y. Berclaz
Journal: European Respiratory Journal (2009)

High inter- and intra-laboratory variability exists for the single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) test. To detect small changes in diffusing capacity in multicentre clinical trials, accurate measurements are essential. The present study assessed whether regular D(L,CO) simulator testing maintained or improved instrument accuracy and reduced variability in multicentre trials. The 125 pulmonary function testing laboratories that participated in clinical trials for AIR(R) Inhaled Insulin validated and monitored the accuracy of their D(L,CO) measuring devices using a D(L,CO) simulator, which creates known target values for any device. Devices measuring a simulated D(L,CO) different from target by >3 mL.min-1.mmHg(-1) failed testing and were serviced. Device accuracy was assessed over time and with respect to differences in several variables. Initially, 31 (25%) laboratories had a D(L,CO) device that failed simulator testing. After fixing or replacing devices, 124 (99%) laboratories had passing devices. The percentage of failed tests significantly decreased over time. Differences in geographical region, device type, breath-hold time, temperature and pressure were not associated with meaningful differences in D(L,CO) device accuracy. Regular diffusing capacity of the lung for carbon monoxide simulator testing allows pulmonary function testing laboratories to maintain the accuracy of their diffusing capacity measurements, leading to reduced variability across laboratories in multicentre clinical trials.
Long-term outcome after primary angioplasty: report from the Primary Angioplasty in Myocardial Infarction (PAMI-I) trial
Authors: Christopher M. Nunn, William W. O’Neill, Donald Rothbaum, Gregg W. Stone, James O’Keefe, Paul Overlie, Bryan Donohue, Lorelei Grines, Kevin F. Browne, Ronald E. Vlietstra, Tom Catlin, Cindy L. Grines
Journal: Journal of the American College of Cardiology (1999)
Tracking the microbiome functionality: focus on<i>Propionibacterium</i>species
Authors: Benoit Foligné, Jérôme Breton, Denis Mater, Gwenaël Jan
Journal: Gut (2013)

We read with great interest the recent study by Dewulf and coworkers1 reporting encouraging results on a prebiotic-based dietary intervention trial in obese patients. This work enlightens that even subtle changes in the gut microbiota may influence the metabolomic signature both inside and outside the gut. Interplay among diet, immunity and microbial and host metabolism results in a complex multidirectional signalling that is critical in the maintenance of a healthy gut functionality, reducing risks for inflammatory bowel diseases and metabo-inflammation states associated with obesity.2 ,3 In parallel, the ‘omics’ era has produced many observations associated with disease states,4 and the correlation among the presence, absence or specific ratios of certain bacterial phyla, orders or genera can be considered as a strategy to directly or indirectly manipulate the microbiome. However, a clear causal molecular link between a specific microbial community and a specific metabolic or immune profile is …
Adaptation to hypoxia in the diabetic rat kidney
Authors: C. Rosenberger, M. Khamaisi, Z. Abassi, V. Shilo, S. Weksler-Zangen, M. Goldfarb, A. Shina, F. Zibertrest, K.-U. Eckardt, S. Rosen, S.N. Heyman
Journal: Kidney International (2007)
Action potential changes under varied [Na+]0 and [Ca2+]0 indicating the existence of two inward currents in cells of the rabbit atrioventricular node.
Authors: E Ruiz-Ceretti, A P Zumino
Journal: Circulation Research (1976)

In the perfused rabbit heart,the upstroke of the transmembrane action potential of fibers of the atrioventricular (AV) node presents two distinct components. The first depends strongly on extracellular sdoium concentration, but the degree to which it is activated is influenced by extracellular calcium, as indicated by the correlation between its Vmax and [Ca2+]0. The second component depends on calcium and sodium concentrations and is blocked by Mn ions. An analysis comparing action potentials from atrial (A), atrionodal (AN), and nodal (N) fibers shows that the second component of the upstroke of the action potential contributes 12%, 27%, and 34% to the total depolarization. The results suggest that the upstroke of the nodal action potential results from the activation of two inward currents, as in ordinary cardiac fibers. We postulate that (1) the degree of steady state inactivation of gNa is larger in N than in A fibers because of the low resting potential of the former, and (2) the contribution of the second channel to the upstroke depends on the time course of the previous depolarization and the potential level at which this component is activated.
Diffuse lung disease: product of genetic susceptibility and environmental encounters
Authors: P. A. Lympany, R. M. du Bois
Journal: Thorax (1997)

Diffuse (interstitial) lung disease comprises a wide variety of conditions, individually relatively uncommon but collectively being found in approximately 50 per 100,000 population. Some of these diseases are of known aetiology but others are not. It has been suggested that the environment is a major contributory factor in this group of diseases. However, since not all individuals exposed to a common environment develop interstitial diseases, it can be hypothesised that there is a genetic predisposition to their development. These diseases cause major morbidity and mortality due to lung injury and fibrosis. It follows that, if individuals who are genetically predisposed to develop diseases characterised by lung injury and fibrosis can be identified, then management strategies can be designed which will attempt to identify and treat early disease and, in the longer term, to develop targeted genetic interventional approaches to treatment.
The Rapid Evolution of X-linked Male-Biased Gene Expression and the Large-X Effect in Drosophila yakuba, D. santomea, and Their Hybrids
Authors: Ana Llopart
Journal: Molecular Biology and Evolution (2012)

The X chromosome has a large effect on hybrid dysfunction, particularly on hybrid male sterility. Although the evidence for this so-called large-X effect is clear, its molecular causes are not yet fully understood. One possibility is that, under certain conditions, evolution proceeds faster in X-linked than in autosomal loci (i.e., faster-X effect) due to both natural selection and their hemizygosity in males, an effect that is expected to be greatest in genes with male-biased expression. Here, I study genome-wide variation in transcript abundance between Drosophila yakuba and D. santomea, within these species and in their hybrid males to evaluate both the faster-X and large-X effects at the level of expression. I find that in X-linked male-biased genes (MBGs) expression evolves faster than in their autosomal counterparts, an effect that is accompanied by a unique reduction in expression polymorphism. This suggests that Darwinian selection is driving expression differences between species, likely enhanced by the hemizygosity of the X chromosome in males. Despite the recent split of the two sister species under study, abundant changes in both cis- and trans-regulatory elements underlie expression divergence in the majority of the genes analyzed, with significant differences in allelic ratios of transcript abundance between the two reciprocal F1 hybrid males. Cis–trans coevolution at molecular level, evolved shortly after populations become isolated, may therefore contribute to explain the breakdown of the regulation of gene expression in hybrid males. Additionally, the X chromosome plays a large role in this hybrid male misexpression, which affects not only MBG but also, to a lesser degree, nonsex-biased genes. Interestingly, hybrid male misexpression is concentrated mostly in autosomal genes, likely facilitated by the rapid evolution of sex-linked trans-acting factors. I suggest that the faster evolution of X-linked MBGs, at both protein and expression levels, contributes to explain the large effect of the X chromosome on hybrid male sterility, likely mediating widespread autosomal misexpression through the preferential recognition of cis-regulatory elements by conspecific trans-acting factors (i.e., cis–trans conspecific recognition).
Data re-entry overload: time for a paradigm shift in maternity IT?
Authors: Rupert Fawdry, Susan Bewley, Grant Cumming, Helga Perry
Journal: Journal of the Royal Society of Medicine (2011)

This paper provides an overview of maternity information technology (IT) in Britain, questioning the usability, effectiveness and cost efficiency of the current models of implementation of electronic maternity records. UK experience of hand-held paper obstetric notes and computerized records reveals fundamental problems in the relationship between the two complementary methods of recording maternity data. The assumption that paper records would inevitably be replaced by electronic substitutes has proven false; the rigidity of analysable electronic records has led to immense incompatibility problems. The flexibility of paper records has distinct advantages that have so far not been sufficiently acknowledged. It is suggested that continuing work is needed to encourage the standardization of electronic maternity records, via a new co-creative, co-development approach and continuing international electronic community debate.
Regulation and Role of Adenylyl Cyclase Isoforms
Authors: Jacques Hanoune, Nicole Defer
Journal: The Annual Review of Pharmacology and Toxicology (2001)

At least nine closely related isoforms of adenylyl cyclases (ACs), the enzymes responsible for the synthesis of cyclic AMP (cAMP) from ATP, have been cloned and characterized in mammals. Depending on the properties and the relative levels of the isoforms expressed in a tissue or a cell type at a specific time, extracellular signals received through the G-protein-coupled receptors can be differentially integrated. The present review deals with various aspects of such regulations, emphasizing the role of calcium/calmodulin in activating AC1 and AC8 in the central nervous system, the potential inhibitory effect of calcium on AC5 and AC6, and the changes in the expression pattern of the isoforms during development. A particular emphasis is given to the role of cAMP during drug and ethanol dependency and to some experimental limitations (pitfalls in the interpretation of cellular transfection, scarcity of the invalidation models, existence of complex macromolecular structures, etc).
Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain
Authors: Junjie U Guo, Yijing Su, Joo Heon Shin, Jaehoon Shin, Hongda Li, Bin Xie, Chun Zhong, Shaohui Hu, Thuc Le, Guoping Fan, Heng Zhu, Qiang Chang, Yuan Gao, Guo-li Ming, Hongjun Song
Journal: Nature Neuroscience (2013)
α7-Nicotinic Acetylcholine Receptors Affect Growth Regulation of Human Mesothelioma Cells
Authors: Sonya Trombino, Alfredo Cesario, Stefano Margaritora, PierLuigi Granone, Giovanni Motta, Carla Falugi, Patrizia Russo
Journal: Cancer Research (2004)

Abstract This study presents data suggesting that both human mesothelioma (cell lines and human mesothelioma biopsies) and human normal mesothelial cells express receptors for acetylcholine and that stimulation of these receptors by nicotine prompted cell growth via activation of nicotinic cholinergic receptors. Thus, these data demonstrate that: (a) human mesothelioma cells and human biopsies of mesothelioma as well as of normal pleural mesothelial cells express functionally α-7 nicotinic acethlycholine receptors, evaluated by α-bungarotoxin-FITC binding, receptor binding assay, Western blot, and reverse transcription-PCR; (b) choline acetyltransferase immunostaining is present in mesothelioma cells; (c) mesothelioma cell growth is modulated by the cholinergic system in which agonists (i.e., nicotine) has a proliferative effect, and antagonists (i.e., curare) has an inhibitory effect, evaluated by cell cloning, DNA synthesis and cell cycle; (d) nicotine induces Ca+2 influx, evaluated by [45Ca2+] uptake, and consequently activation of mitogen-activated protein kinase pathway (extracellular signal-regulated kinase and p90RSK phosphorylation), evaluated by Western blot; and (e) apoptosis mechanisms in mesothelioma cells are under the control of the cholinergic system (nicotine antiapoptotic via induction of nuclear factor-κB complexes and phosphorylation of Bad at Ser112; curare proapoptotic via G0-G1 arrest p21waf-1 dependent but p53 independent). The involvement of the nonneuronal cholinergic system in mesothelioma appears reasonable and open up new therapeutic strategies.
Loss of Heterozygosity at D14S62 and Metastatic Potential of Breast Cancer
Authors: P O'Connell, K Fischbach, S Hilsenbeck, S K Mohsin, S A Fuqua, G M Clark, C K Osborne, D C Allred
Journal: JNCI Journal of the National Cancer Institute (1999)

In breast cancer progression, the prevalence of damage at specific genetic loci often increases with the stage of the lesion (i.e., from noninvasive to invasive to metastatic). By use of genetic markers and analysis of allelic imbalances (loss of heterozygosity [LOH]) to compare DNA samples from paired normal and breast tumor tissues, we examined whether specific genetic changes in primary breast cancers can serve as biomarkers of metastatic potential.DNA samples from 76 patients with primary breast cancer (42 with axillary lymph node-negative disease and 34 with axillary lymph node-positive disease) were genotyped with four genetic markers spanning chromosome 14q31-q32. The intensity ratios of the two genetic alleles in normal-tumor DNA pairs were examined in genetically informative individuals. LOH was scored when the tumor allele intensity ratio (tumor allele 1/tumor allele 2) divided by the normal allele intensity ratio (normal allele 1/normal allele 2) was either less than 0.71 (tumor allele 1 LOH) or greater than 1. 4 (tumor allele 2 LOH).Contrary to our expectations, we found statistically significantly more LOH events at markers D14S62 (two-sided P =.001) and D14S51 (two-sided P =.02) in primary breast cancers from patients with lymph node-negative disease versus lymph node-positive disease, suggesting the presence of a gene in this region that affects metastatic potential. Analysis of small interstitial or terminal deletions in the tumors of six especially informative patients with lymph node-negative disease places the putative metastasis-related gene in a 1490-kilobase region near D14S62.LOH in the D14S62 region may impede the process of metastasis. Therefore, the D14S62 region LOH profile may have prognostic implications, and the isolation of the metastasis-related gene(s) in this region may lead to better diagnosis and treatment of breast cancer.
Finding of Kinase Domain Mutations in Patients With Chronic Phase Chronic Myeloid Leukemia Responding to Imatinib May Identify Those at High Risk of Disease Progression
Authors: Jamshid S. Khorashad, Hugues de Lavallade, Jane F. Apperley, Dragana Milojkovic, Alistair G. Reid, Marco Bua, Richard Szydlo, Eduardo Olavarria, Jaspal Kaeda, John M. Goldman, David Marin
Journal: Journal of Clinical Oncology (2008)

Kinase domain (KD) mutations in the BCR-ABL gene are associated with resistance to imatinib in chronic myeloid leukemia (CML) but their incidence and prognostic significance in chronic phase (CP) patients without resistance are unclear.We analyzed outcome for 319 patients with CML-CP who were treated with imatinib; 171 were in early CP (ECP) and 148 were in late CP (LCP). Patients were screened routinely for mutations using direct sequencing regardless of response status. The 5-year cumulative incidence of mutations was 6.6% for ECP and 17% for LCP patients.Of the 319 patients, 214 (67%) achieved complete cytogenetic responses (CCyR). The identification of a mutation without other evidence of imatinib resistance was highly predictive for loss of CCyR (RR, 3.8; P = .005) and for progression to advanced phase (RR, 2.3; P = .01), though the intervals from first identification to loss of CCyR and disease progression were relatively long (median, 21 and 16 months, respectively). Mutations in the P-loop (excluding residue 244) were associated with a higher risk of progression than mutations elsewhere.We conclude that routine mutation screening of patients who appear to be responding to imatinib may identify those at high risk of disease progression.
Note on Viburnum Prunifolium in Abortion
Authors: W. M. Campbell
Journal: BMJ (1886)

ptoms were only developed contemporaneously with the cereoral disturbances, and I believe they are but the mechanical expression of increased intracranial pressure.I have, on more than one occasion, seen patients who were suffering from acute symptoms of lead-poisoning, whose discs I had examined in the morning and found normal, the same evening became the victims of the most acute cerebral sym- ptoms.Violent epileptiform convulsions, dilated pupils, blindness, exhibit a well inarked " Stauungs-papilla," or choked disc.I have known these patients pass into a semi-comatose condition, and remain so for several days, anid then gradually recover, with impaired mental faculties and different degrees of blindness.
MS4A12 Is a Colon-Selective Store-Operated Calcium Channel Promoting Malignant Cell Processes
Authors: Michael Koslowski, Ugur Sahin, Karl Dhaene, Christoph Huber, Özlem Türeci
Journal: Cancer Research (2008)

Abstract Using a data mining approach for the discovery of new targets for antibody therapy of colon cancer, we identified MS4A12, a sequence homologue of CD20. We show that MS4A12 is a cell surface protein. Expression analysis and immunohistochemistry revealed MS4A12 to be a colonic epithelial cell lineage gene confined to the apical membrane of colonocytes with strict transcriptional repression in all other normal tissue types. Expression is maintained upon malignant transformation in 63% of colon cancers. Ca2+ flux analyses disclosed that MS4A12 is a novel component of store-operated Ca2+ entry in intestinal cells. Using RNAi-mediated gene silencing, we show that loss of MS4A12 in LoVo colon cancer cells attenuates epidermal growth factor receptor–mediated effects. In particular, proliferation, cell motility, and chemotactic invasion of cells are significantly impaired. Cancer cells expressing MS4A12, in contrast, are sensitized and respond to lower concentrations of epidermal growth factor. In summary, these findings have implications for both the physiology of colonic epithelium as well as for the biology and treatment of colon cancer. [Cancer Res 2008;68(9):3458–66]
The Global Health System: Lessons for a Stronger Institutional Framework
Authors: Suerie Moon, Nicole A. Szlezák, Catherine M. Michaud, Dean T. Jamison, Gerald T. Keusch, William C. Clark, Barry R. Bloom
Journal: PLoS Medicine (2010)

This is the fourth in a series of four articles that highlight the changing nature of global health institutions.The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies.