tbuckley/cabot-search huggingface dataset:
Regulation of Selenium Metabolism and Transport
Authors: Raymond F. Burk, Kristina E. Hill
Journal: Annual Review of Nutrition (2015)

Selenium is regulated in the body to maintain vital selenoproteins and to avoid toxicity. When selenium is limiting, cells utilize it to synthesize the selenoproteins most important to them, creating a selenoprotein hierarchy in the cell. The liver is the central organ for selenium regulation and produces excretory selenium forms to regulate whole-body selenium. It responds to selenium deficiency by curtailing excretion and secreting selenoprotein P (Sepp1) into the plasma at the expense of its intracellular selenoproteins. Plasma Sepp1 is distributed to tissues in relation to their expression of the Sepp1 receptor apolipoprotein E receptor-2, creating a tissue selenium hierarchy. N-terminal Sepp1 forms are taken up in the renal proximal tubule by another receptor, megalin. Thus, the regulated whole-body pool of selenium is shifted to needy cells and then to vital selenoproteins in them to supply selenium where it is needed, creating a whole-body selenoprotein hierarchy.
Use of a solid-phase radioimmunoassay and formalin-fixed whole bacterial antigen in the detection of antigen-specific immunoglobulin in prostatic fluid.
Authors: L M Shortliffe, N Wehner, T A Stamey
Journal: Journal of Clinical Investigation (1981)

The prostatic fluid of two patients with Escherichia coli bacterial prostatitis was analyzed for evidence of a local immune response to bacterial infection. A solid-phase radioimmunoassay was modified to measure the immunoglobulin (Ig)A and IgG antigen-specific antibody responses to infecting bacteria in serum and prostatic fluid from patient. Formalin-fixed whole E. coli were used as antigen. In one patient with acute E. coli prostatic infection, measurements of antigen-specific antibody confirm the presence of a systemic and local immune response. However, in another patient with a chronic E. coli prostatitis, a primarily local immune response was demonstrated. The response measured in the prostatic fluid appears to be locally stimulated and specific for the infecting bacteria. Furthermore, IgA was the predominant immunoglobulin involved in the local prostatic immune response to infection. Although elevations of serum IgA antigen-specific antibody levels were short-liver after treatment of prostatic infection, local IgA antigen-specific antibodies were detected for as long as 1 yr after the initial infection in both patients studied.
Robert Willan and the French Willanists
Authors: None Tilles, None Wallach
Journal: British Journal of Dermatology (1999)

In 1798, Robert Willan published the founding textbook of British dermatology. In adopting the elementary lesions principle previously described by Josef Plenck and improving the nomenclature of the skin diseases, Willan established a method for the diagnosis and a doctrine for the nosology of the cutaneous diseases. Introduced into France by Biett in the 1810s, the Willanist method, which allowed diagnosis on the basis of objective criteria, was adopted by the majority of the dermatological community. However, as a doctrine, Willanism, the use of elementary lesions as a framework for classifying diseases, became the subject of lasting debate. In fact, apart from a few, most leading French dermatologists did not accept Willan's doctrine and preferred classifications according to systems which were supposed to reflect the best understanding of the cutaneous diseases: physiological, aetiological and pathological. Willanism is still used by every dermatologist as a method for recognizing skin diseases. It constitutes a firm link to the founding period of modern dermatology and remains a bastion against uncertain hypotheses.
Effect of sustained release terbutaline on symptoms and sleep quality in patients with nocturnal asthma.
Authors: I C Stewart, G B Rhind, J T Power, D C Flenley, N J Douglas
Journal: Thorax (1987)

The effect of an oral sustained release beta 2 agonist on symptoms, sleep quality, and peak flow rates has been studied in nine patients with nocturnal asthma. Patients received oral terbutaline 7.5 mg twice daily or placebo for seven days in a double blind crossover study and spent the last two nights of each limb in a sleep laboratory. Oral terbutaline improved morning peak flow (259 v 213 l min-1) and decreased nocturnal inhaler usage (1.3 v 1.9) with no alteration in sleep quality as assessed electroencephalographically. The study shows that oral sustained release terbutaline can be useful in the treatment of nocturnal asthma without impairment of sleep quality.
Hippocampal Changes in Patients With a First Episode of Major Depression
Authors: Thomas Frodl, Eva M. Meisenzahl, Thomas Zetzsche, Christine Born, Constanze Groll, Markus Jäger, Gerda Leinsinger, Ronald Bottlender, Klaus Hahn, Hans-Jürgen Möller
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Previous work suggests that patients with unipolar depression may have structural as well as functional abnormalities in limbic-thalamic-cortical networks, which are hypothesized to modulate human mood states. A core area in these networks is the hippocampus. In the present study, differences in volumes of hippocampal gray and white matter between patients with a first episode of major depression and healthy comparison subjects were examined. METHOD: Thirty patients with a first episode of major depression and 30 healthy comparison subjects who were matched for age, gender, handedness, and education were examined with high-resolution magnetic resonance imaging. RESULTS: Male patients with a first episode of major depression had significantly smaller hippocampal total and gray matter volumes than healthy male comparison subjects. Both male and female patients showed significant alterations of left-right asymmetry and significant reductions of left and right hippocampal white matter fibers in relation to healthy comparison subjects. Hippocampal measurements were not significantly correlated with clinical variables, such as age at onset of illness, illness duration, or severity of depression. CONCLUSIONS: These results are consistent with findings of structural abnormalities of the hippocampal formation in patients with major depression that were more pronounced in male patients. The authors’ findings support the hypothesis that the hippocampus and its connections within limbic-cortical networks may play a crucial role in the pathogenesis of major depression.
Interaction between calcium, neutral endopeptidase and the substance P mediated ciliary response in human respiratory epithelium
Authors: RP Smith, R Shellard, G Di Benedetto, CJ Magnus, A Mehta
Journal: European Respiratory Journal (1996)

Following irritation of the airway, the ciliostimulatory effects of the tachykinin, substance P (SP), are thought to be secondary to mucus release. We hypothesized that SP also induces small increases in ciliary beat frequency (CBF) via a calcium-mediated process. Brushed ciliated cells from the nasal epithelium of healthy human subjects were suspended in tissue culture fluid and the acute effects of SP upon these cells were studied in a mucus-free environment. In some preparations, changes in CBF in response to SP were measured with a video-based system. The effect of an SP antagonist, of Ca2+ channel block with verapamil, and of the calcium analogue lanthanum on the SP response were also tested. In other preparations, the ciliated cells were preloaded with Fura-2, a dye which fluoresces with Ca2+ ions, and the response of intracellular Ca2+ to SP was monitored. SP (10(-9)-10(-6) M) transiently increased CBF in a dose-dependent manner, with the maximal response occurring at 10 min. The response was small, with a maximum increase of 8.9%. The SP receptor antagonist (D-pro2,D-trp7,9)-SP (10(-5) M) abolished this effect. Verapamil (10(-5) M) attenuated the response to SP (10(-7) M), whilst lanthanum chloride (250 microM) abolished it. Inhibition of SP destruction by phosphoramidon (10(-6) M) also eliminated the transient rise in CBF. However, compared to SP alone, the combination of SP and phosphoramidon induced a novel delayed lanthanum-sensitive rise in CBF. In other experiments, SP (10(-7) M) induced a transient increase in free intracellular Ca2+ concentration (maximal rise 73%), which returned to baseline before the expected onset of the CBF response. We conclude that substance P induces either a transient or sustained increase in CBF dependent on the rate of destruction of this peptide around tachykinin receptors. These receptors are likely to be linked to lanthanum- and verapamil-sensitive pathways for the entry of Ca2+ into cells. The small magnitude of the rise in CBF makes its physiological role uncertain at present.
The draft genome of the carcinogenic human liver fluke Clonorchis sinensis
Authors: Xiaoyun Wang, Wenjun Chen, Yan Huang, Jiufeng Sun, Jingtao Men, Hailiang Liu, Fang Luo, Lei Guo, Xiaoli Lv, Chuanhuan Deng, Chenhui Zhou, Yongxiu Fan, Xuerong Li, Lisi Huang, Yue Hu, Chi Liang, Xuchu Hu, Jin Xu, Xinbing Yu
Journal: Genome biology (2011)

Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome.We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines.This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control.
Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients with Multiple Myeloma
Authors: Roberto Ria, Katia Todoerti, Simona Berardi, Addolorata Maria Luce Coluccia, Annunziata De Luisi, Michela Mattioli, Domenica Ronchetti, Fortunato Morabito, Attilio Guarini, Maria Teresa Petrucci, Franco Dammacco, Domenico Ribatti, Antonino Neri, Angelo Vacca
Journal: Clinical Cancer Research (2009)

To determine a "gene/molecular fingerprint" of multiple myeloma endothelial cells and identify vascular mechanisms governing the malignant progression from quiescent monoclonal gammopathy of undetermined significance.Comparative gene expression profiling of multiple myeloma endothelial cells and monoclonal gammopathy of undetermined significance endothelial cells with the Affymetrix U133A Arrays was carried out in patients at diagnosis; expression and function of selective vascular markers was validated by real-time reverse transcriptase-PCR, Western blot, and small interfering RNA analyses.Twenty-two genes were found differentially expressed (14 down-regulated and eight up-regulated) at relatively high stringency in multiple myeloma endothelial cells compared with monoclonal gammopathy of undetermined significance endothelial cells. Functional annotation revealed a role of these genes in the regulation of extracellular matrix formation and bone remodeling, cell adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Validation was focused on six genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3, and SEPW1) not previously found to be functionally correlated to the overangiogenic phenotype of multiple myeloma endothelial cells in active disease. The small interfering RNA knockdown of BNIP3, IER3, and SEPW1 genes affected critical multiple myeloma endothelial cell functions correlated with the overangiogenic phenotype.The distinct endothelial cell gene expression profiles and vascular phenotypes detected in this study may influence remodeling of the bone marrow microenvironment in patients with active multiple myeloma. A better understanding of the linkage between plasma cells and endothelial cells in multiple myeloma could contribute to the molecular classification of the disease and thus pinpoint selective gene targets for more effective antiangiogenic treatments.
Potentiation by granulocyte macrophage colony-stimulating factor of lipopolysaccharide toxicity in mice.
Authors: G Tiegs, J Barsig, B Matiba, S Uhlig, A Wendel
Journal: Journal of Clinical Investigation (1994)

GM-CSF is known to prime leukocytes for inflammatory stimuli in vitro. The objective of this study was to investigate the role of GM-CSF in vivo in a systemic inflammatory reaction syndrome. The results demonstrate a potentiation of LPS toxicity by GM-CSF in a mortality model as well as in a septic liver failure model in mice. Pretreatment of animals with 50 micrograms/kg GM-CSF induced lethality within 24 h in mice challenged with a subtoxic dose of LPS while controls survived > 72 h. A monoclonal anti-GM-CSF antibody significantly protected against a lethal LPS dose. Serum GM-CSF was inducible by LPS and peaked at 2 h. GM-CSF pretreatment dramatically potentiated systemic TNF release and hepatotoxicity induced by a subtoxic dose of LPS in galactosamine-sensitized mice. Potentiation of LPS hepatotoxicity was possible until 30 min after LPS challenge. Polyclonal anti-GM-CSF IgG protected against septic liver failure in this model and attenuated serum TNF concentrations. In vitro an ex vivo experiments revealed that after GM-CSF pretreatment LPS-induced IL-1 release from bone marrow or spleen cells was also enhanced. These findings suggest that GM-CSF represents an endogenous enhancer of LPS-induced organ injury, possibly by potentiating the release of proinflammatory cytokines such as TNF and IL-1.
Tumor Genetic Analyses of Patients with Metastatic Melanoma Treated with the BRAF Inhibitor Dabrafenib (GSK2118436)
Authors: Katherine L. Nathanson, Anne-Marie Martin, Bradley Wubbenhorst, Joel Greshock, Richard Letrero, Kurt D'Andrea, Steven O'Day, Jeffrey R. Infante, Gerald S. Falchook, Hendrik-Tobias Arkenau, Michael Millward, Michael P. Brown, Anna Pavlick, Michael A. Davies, Bo Ma, Robert Gagnon, Martin Curtis, Peter F. Lebowitz, Richard Kefford, Georgina V. Long
Journal: Clinical Cancer Research (2013)

Dabrafenib is a selective inhibitor of V600-mutant BRAF kinase, which recently showed improved progression-free survival (PFS) as compared with dacarbazine, in metastatic melanoma patients. This study examined potential genetic markers associated with response and PFS in the phase I study of dabrafenib.Baseline (pretreatment or archival) melanoma samples were evaluated in 41 patients using a custom genotyping melanoma-specific assay, sequencing of PTEN, and copy number analysis using multiplex ligation amplification and array-based comparative genomic hybridization. Nine patients had on-treatment and/or progression samples available.All baseline patient samples had BRAF(V600E/K) confirmed. Baseline PTEN loss/mutation was not associated with best overall response to dabrafenib, but it showed a trend for shorter median PFS [18.3 (95% confidence interval, CI, 9.1-24.3) vs. 32.1 weeks (95% CI, 24.1-33), P=0.059]. Higher copy number of CCND1 (P=0.009) and lower copy number of CDKN2A (P=0.012) at baseline were significantly associated with decreased PFS. Although no melanomas had high-level amplification of BRAF, the two patients with progressive disease as their best response had BRAF copy gain in their tumors.Copy number changes in CDKN2A, CCND1, and mutation/copy number changes in PTEN correlated with the duration of PFS in patients treated with dabrafenib. The results suggest that these markers should be considered in the design and interpretation of future trials with selective BRAF inhibitors in advanced melanoma patients.
Ethics review roulette: what can we learn?
Authors: P. Glasziou
Journal: BMJ (2004)

<h3>Background</h3> The Syrian Civil War has caused over 400 000 traumatic deaths. Understanding the nature of war casualties is crucial to deliver healthcare improvement. Historic regional conflicts and Syrian mortality data have been characterised by blast injuries. The aim of this novel review is to assess the trauma epidemiology of Syrian Civil War casualties from the perspective of healthcare facilities. <h3>Methods</h3> This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. Studies addressing Syria, trauma and war were investigated. Eligibility criteria included being conducted from a healthcare facility, published in English and peer reviewed. The outcomes were demography, mechanism of injury and anatomical injury site. <h3>Results</h3> 38 papers satisfied the eligibility criteria. 13 842 casualties were reported across the entire data set. Casualties were 88.8% male (n=4035 of 4544). Children contributed to 16.1% of cases (n=398 of 2469). Mortality rate was 8.6% (n=412 of 4774). Gunshot wound was the most common mechanism of injury representing 66.3% (n=7825 of 11799). Head injury was the most common injured site at 26.6% (n=719 of 2701). <h3>Conclusions</h3> This conflict has a distinct trauma profile compared with regional modern wars. The prevalence of gunshot wounds represents a marked change in mechanism of injury. This may be related to higher mortality rate and proportion of head injuries identified. This review cannot correlate mechanism of injury, demographics or injuries sustained to outcomes. The quality of data from the included studies lacked standardisation; future research and consistent reporting tools are required to enable further analysis.
Injectable Silk Foams for Soft Tissue Regeneration
Authors: Evangelia Bellas, Tim J. Lo, Eric P. Fournier, Joseph E. Brown, Rosalyn D. Abbott, Eun S. Gil, Kacey G. Marra, J. Peter Rubin, Gary G. Leisk, David L. Kaplan
Journal: Advanced Healthcare Materials (2014)

Soft tissue fillers are needed for restoration of a defect or augmentation of existing tissues. Autografts and lipotransfer have been under study for soft tissue reconstruction but yield inconsistent results, often with considerable resorption of the grafted tissue. A minimally invasive procedure would reduce scarring and recovery time as well as allow the implant and/or grafted tissue to be placed closer to existing vasculature. Here, the feasibility of an injectable silk foam for soft tissue regeneration is demonstrated. Adipose-derived stem cells survive and migrate through the foam over a 10-d period in vitro. The silk foams are also successfully injected into the subcutaneous space in a rat and over a 3-month period integrating with the surrounding native tissue. The injected foams are palpable and soft to the touch through the skin and returning to their original dimensions after pressure is applied and then released. The foams readily absorb lipoaspirate making the foams useful as a scaffold or template for existing soft tissue filler technologies, useful either as a biomaterial alone or in combination with the lipoaspirate.
Imaging of chronic sinusitis in adults: X-ray, computed tomography, and magnetic resonance imaging
Authors: S.James Zinreich
Journal: Journal of Allergy and Clinical Immunology (1992)

Two decades ago, otolaryngologists became aware that greater attention should be given to the area of the anterior ethmoid sinus. Before then, the maxillary sinus was the primary focus of attention. This was the site at which most surgical procedures were performed on patients with chronic sinusitis (Caldwell-Luc, nasal antrostomy, and irrigation procedures).’ A better understanding of the mucociliary clearance of the nasal cavity and paranasal sinuses underscores the shift in attention to the anterior ethmoid sinus.‘-’ Procto? believed that the seat of infectious disease in the nasal cavity and paranasal sinuses resided in the anterior ethmoid sinus. He suggested that disease in the anterior ethmoid sinus area was the cause of secondary inflammatory disease in the frontal and maxillary sinus. Messerklinge?, 6 was the first to use endoscopes to demonstrate the mucociliary pattern in the nasal cavity and paranasal sinuses, thus confirming Proctor’s beliefs. Messerklinger’s use of telescopes led to the innovative surgical technique of functional endoscopic surgery. The key to most inflammatory sinus disease is the air passage lateral to the middle turbinate, the middle meatus, and the communication with the adjacent sinuses through their respective ostia (ostiomeatal complex) (Fig. 1).‘.4,” The role of mucociliary clearance as it relates to the ostiomeatal complex is less well defined than the major functions of the nasal passages. However, a complete understanding of this area and the pattern of mucociliary clearance is crucial. The ostiomeatal complex is composed of narrow channels and is subject to wide normal anatomic variation (Fig. 2). It contains the ostia needed not only for the drainage of the anterior ethmoid sinuses but also for the frontal and maxillary sinuses. These sinuses are therefore dependent on the integrity of the
Animal models in the study of myocardial ischaemia and ischaemic syndromes
Authors: P Verdouw
Journal: Cardiovascular Research (1998)

Time for primary review 29 days.

Although myocardial ischaemia has been one of the most extensively studied topics in cardiovascular research, its definition is still debated [1]. In the strictest sense ‘ischaemia’ derived from the Greek words, ischo (to restrain) and haima (blood), means insufficient blood, and if we would adhere to this definition, all animal models which lack blood (e.g. isolated heart models) should by definition be termed ‘ischaemic'. Most investigators prefer to define ischaemia as an imbalance between the amount of oxygen and substrates supplied to the heart and the amount needed to perform normal function [1, 2]. The rationale behind this definition is that the myocardium strongly depends on oxygen to sustain adequate oxidative phosphorylation, the only metabolic process that is capable of providing sufficient high energy phosphates to maintain normal myocardial contraction. When oxygen supply to the heart becomes impaired there will be inadequate production of high energy phosphates with a resultant decline in myocardial contractility. When this condition develops, the myocardium starts to produce some, but not sufficient, high energy phosphates by anaerobic glycolysis, and lactate which is the end-product of this process starts to accumulate in the myocardium. Myocardial ischaemia is thus viewed as a condition in which an imbalance exists between oxygen-supply and oxygen-demand, leading to anaerobic metabolism and reduced contractile function. Central to the definition of ischaemia is that coronary flow is not only insufficient to allow adequate energy production, but that the impaired flow also results in impaired removal of metabolic waste products. In the large majority of cases in man myocardial ischaemia is confined to specific regions of the myocardium (regional ischaemia), because a stenosis in a coronary artery prevents adequate perfusion of the artery's distribution area (supply ischaemia). In its early stage of development, the stenosis can … 

* Corresponding author. Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Tel.: +31-10-408-8029; Fax: +31-10-436-5607; E-mail: verdouw@tch.fgg.eur.nl