tbuckley/cabot-search huggingface dataset:
The effect of neuromuscular blockade on oxygen consumption in sedated and mechanically ventilated pediatric patients after cardiac surgery
Authors: J. Lemson, J. J. Driessen, J. G. van der Hoeven
Journal: Intensive Care Medicine (2008)

To measure the effect of intense neuromuscular blockade (NMB) on oxygen consumption (VO(2)) in deeply sedated and mechanically ventilated children on the first day after complex congenital cardiac surgery. Prospective clinical interventional study. Pediatric intensive care unit of an university medical centre. Nine mechanically ventilated and sedated children (weight 2.8-8.7 kg) were included. All children were treated with vasoactive drugs. The level of sedation was quantified using the comfort score, Ramsay score and bispectral index (BIS). The intensity of NMB was quantified using acceleromyography and VO(2) was measured using indirect calorimetry. Analgo-sedation using various intravenous agents was targeted at a deep level (comfort score < 18, BIS < 60 and Ramsay score > 4). NMB was achieved by intravenous administration of rocuronium. All measurements were conducted before, during and after recovery from a period of intense NMB. Baseline values were VO(2) 6.1 ml/(kg min) (SD 1.3), comfort score 13 (SD 0.7), BIS 42.5 (SD 14.2), mean blood pressure 54.0 mmHg (SD 10.5), mean heart rate 129.9 bpm (SD 28.9) and mean core temperature 36.7 degrees C (SD 0.5). There were no significant differences in VO(2) or other parameters between baseline, during NMB and the recovery phase. Neuromuscular blocking agents do not reduce oxygen consumption in deeply sedated and mechanically ventilated children after congenital cardiac surgery.
Acetylation of cyclophilin A is required for its secretion and vascular cell activation
Authors: Nwe Nwe Soe, Mark Sowden, Padmamalini Baskaran, Yeonghwan Kim, Patrizia Nigro, Elaine M. Smolock, Bradford C. Berk
Journal: Cardiovascular Research (2013)

Cyclophilin A (CyPA) is a pro-inflammatory mediator involved in oxidative stress-related cardiovascular diseases. It is secreted from vascular smooth muscle cell (VSMC) in response to reactive oxygen species (ROS) in a highly regulated manner. Extracellular CyPA activates VSMCs and endothelial cells (ECs) promoting inflammation, cell growth, and cell death. Recently, it was shown that acetylated CyPA (AcK-CyPA) affects its function. We investigated the role of acetylation of CyPA for its secretion and signalling in vascular cells. We used angiotensin II (Ang II) to create sustained ROS and found significantly increased AcK-CyPA in VSMC. Site-directed mutagenesis showed that lysines K82 and K125 were the predominant CyPA residues acetylated in response to Ang II. Importantly, acetylation of K82 and K125 were required for Ang II-mediated CyPA secretion. ROS inhibitors, Tiron, and N-acetylcysteine inhibited Ang II-induced intracellular CyPA acetylation and also AcK-CyPA secretion. Using secreted CyPA from wild type and K82/125R mutants expressed in transduced VSMC or in vitro acetylated recombinant CyPA, we showed that extracellular AcK-CyPA significantly increased pERK1/2, matrix metalloproteinase-2 activation, and ROS production in VSMC compared with non-acetylated CyPA. Moreover, extracellular AcK-CyPA increased adhesion molecule expression (VCAM-1 and ICAM-1) in EC, which promoted monocyte adhesion. ROS-dependent acetylation of CyPA is required for the generation of extracellular CyPA. Acetylated extracellular CyPA regulates VSMC and EC activation, suggesting that inhibition of acetylation of CyPA may prevent the pathogenesis of oxidative stress-related cardiovascular diseases.
The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination.
Authors: G R Bernard, A Artigas, K L Brigham, J Carlet, K Falke, L Hudson, M Lamy, J R Legall, A Morris, R Spragg
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.
Different modes of Mhc evolution in primates.
Authors: J Klein, C O'hUigin, F Figueroa, W E Mayer, D Klein
Journal: Molecular Biology and Evolution (1993)

The human major histocompatibility complex (Mhc) is a chromosomal segment approximately 4 million bp long that contains > or = 84 genes. Some of these genes code for the class I and class II molecules, while the remaining genes code for complement components, cytochrome P450, tumor necrosis factor, and many other, unrelated proteins. We demonstrate on three examples (DP, C4-CYP21, and DRB) that different regions of the Mhc have different evolutionary histories. The organization of the DP region, which in humans contains four genes, was established in the ancestral Anthropoidea or earlier and has not changed since. The duplication that generated the two C4-CYP21 modules occurred in the ancestral Catarrhini or earlier, but the region has been undergoing periodic homogenizations via unequal crossing-over, which make paralogous genes in the same species more similar to each other than to orthologous genes of different species. The eight or nine genes of the DRB region were also generated in the ancestral Catarrhini, but the region has since been subject to frequent rearrangements, which generated various DRB haplotypes. Not only the alleles but, in part, also the haplotype polymorphism is evolving transspecifically. The DRB region of the Platyrrhini has an origin different from that of the Catarrhini. The picture emerging from these studies is that of both stability in some regions of the Mhc and tremendous evolutionary instability in other regions.
T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis.
Authors: E Scotet, J David-Ameline, M A Peyrat, A Moreau-Aubry, D Pinczon, A Lim, J Even, G Semana, J M Berthelot, R Breathnach, M Bonneville, E Houssaint
Journal: The Journal of Experimental Medicine (1996)

Rheumatoid arthritis is a multistep disorder associated with autoimmune features of yet unknown etiology. Implication of viruses such as Epstein-Barr virus (EBV) in rheumatoid arthritis pathogenesis has been suspected on the basis of several indirect observations, but thus far, a direct link between EBV and rheumatoid arthritis has not been provided. Here we show that a large fraction of T cells infiltrating affected joints from a patient with chronic rheumatoid arthritis recognizes two EBV transactivators (BZLF1 and BMLF1) in a major histocompatibility complex-restricted fashion. Responses to these EBV antigens by synovial lymphocytes from several other chronic rheumatoid arthritis patients were readily detectable. Thus these results suggest a direct contribution of EBV to chronic rheumatoid arthritis pathogenesis. They also demonstrate for the first time the occurrence of T cell responses against EBV transactivating factors, which might be central in the control of virus reactivation.
An Address on the Study of Human Anatomy
Authors: None Humphry
Journal: BMJ (1887)

tM .IC4JfR rl. 14 1t3S, wq was-killed by.an aceident equvincod me that the former were' oelately normal in microseopical appearance.I have alsov 4xA1in1 ',4e,medulla and supra-renal capsule of the case in whch i brl Symptoms developed, but wvith negative result.The view, Vwlitk I *v disposed to lean is, that the majority of the case of Graves's *4iease are examples of a functional neurosis of the sympathetic And perhaps of the associated centres in the cord and medulla (especially ,the latter).In proof of the functiotal, in opposition to' the Qrganic,
Effect of four weeks' high dose ipratropium bromide treatment on lung mucociliary clearance.
Authors: R G Taylor, D Pavia, J E Agnew, M T Lopez-Vidriero, S P Newman, T Lennard-Jones, S W Clarke
Journal: Thorax (1986)

In a randomised, double blind crossover study the effect of high dose ipratropium bromide (200 micrograms three times daily given by metered dose inhaler for four weeks) on lung mucociliary clearance and on the wet weight and mean apparent viscosity of sputum was compared with that of placebo. Six smokers, six ex-smokers, and three non-smokers (12 men and three women, median age 60 years) were studied. Eight subjects had chronic obstructive lung disease (median FEV1 46% predicted) and seven had asthma (FEV1 70% predicted). Seven subjects produced sputum regularly, two of whom had asthma. Clearance of secretions was measured by an inhaled radioaerosol technique. The number of coughs and the wet weight, radioactive content, and mean apparent viscosity of sputum produced during the six hour observation period were recorded, as was the mean wet weight of sputum produced during the last two 24 hour periods ending each treatment. Comparison with placebo showed that treatment with high dose ipratropium bromide was associated with a significant increase in the penetration index of inhaled particles, but there was no significant change in alveolar deposition of particles or in tracheobronchial clearance, uncorrected or corrected for sputum expectorated. The wet weight of sputum produced, its radioactive content, and mean apparent viscosity were similar after treatment with ipratropium bromide and placebo. These results show that high dose inhaled treatment with the synthetic anticholinergic bronchodilator ipratropium bromide for four weeks is not associated with detectable modification of the clearance of secretions from the lungs, or of sputum volume or viscosity.
The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest
Authors: S. Jonard
Journal: Human Reproduction Update (2004)

This review exposes the follicular abnormalities responsible for anovulation in polycystic ovary syndrome (PCOS). The putative pathophysiological explanations involve the principal intra‐ and extra‐ovarian regulators which intervene during normal folliculogenesis to control the initial recruitment and growth and then the cyclic recruitment. We propose the hypothesis that the follicular problem in PCOS is 2‐fold, but with the two abnormalities being linked. First, the intra‐ovarian hyperandrogenism may promote early follicular growth, leading to a 2–5 mm follicle excess. Second, the ensuing excessive number of selectable follicles would inhibit the selection process, presumably through follicle–follicle interaction involving granulosa cell (GC) products such as the anti‐Müllerian hormone (AMH). These factors would induce a reversible refractoriness to the FSH‐induced differentiation of GC. This explanation challenges but does not exclude other hypotheses about the follicular arrest, such as the premature LH action on the GC of selectable follicles. Hyperinsulinism or insulin resistance would act as a second hit, worsening the follicular arrest either through amplification of the intra‐ovarian hyperandrogenism or through dysregulation of the GC. The loss of cyclic rhythm would prevent the inter‐cycle elevation of FSH, thus perpetuating the impairment of the ovulation process.
CD164 regulates the tumorigenesis of ovarian surface epithelial cells through the SDF-1α/CXCR4 axis
Authors: Ai-Fang Huang, Min-Wei Chen, Shih-Ming Huang, Chu-Lien Kao, Hung-Cheng Lai, James Yi-Hsin Chan
Journal: Molecular Cancer (2013)

Abstract Background CD164 (endolyn), a sialomucin, has been reported to play a role in the proliferation, adhesion, and differentiation of hematopoietic stem cells. The potential association of CD164 with tumorigenicity remains unclear. Methods The clinicopathological correlation of ovarian cancer with CD164 was assessed in a 97-patient tumor tissue microarray. Overexpression or silence CD164 was to analyze the effect of CD164 on the proliferation, colony formation and apoptosis via a mouse xenograft and western blotting analysis. The subcellular localization of CD164 was collected in the immunohistochemical and confocal analysis. Results Our data demonstrated that higher expression levels of CD164 were identified in malignant ovarian cancer cell lines, such as SKOV3 and HeyA8. The clinicopathological correlation analysis showed that the upregulation of CD164 protein was significantly associated with tumor grade and metastasis. The overexpression of CD164 in human ovarian epithelial surface cells promoted cellular proliferation and colony formation and suppressed apoptosis. These tumorigenicity effects of CD164 were reconfirmed in a mouse xenograft model. We also found that the overexpression of CD164 proteins increased the amounts of CXCR4 and SDF-1α and activated the SDF-1α/CXCR4 axis, inducing colony and sphere formation. Finally, we identified the subcellular localization of CD164 in the nucleus and cytosol and found that nuclear CD164 might be involved in the regulation of the activity of the CXCR4 promoter. Conclusions Our findings suggest that the increased expression of CD164 is involved in ovarian cancer progression via the SDF-1α/CXCR4 axis, which promotes tumorigenicity. Thus, targeting CD164 may serve as a potential ovarian cancer biomarker, and targeting CD164 may serve as a therapeutic modality in the management of high-grade ovarian tumors.
Fibroblast Growth Factor Receptor 3 Is Overexpressed in Urinary Tract Carcinomas and Modulates the Neoplastic Cell Growth
Authors: J. Javier Gómez-Román, Pilar Saenz, Jorge Cuevas González, Kepa Escuredo, Simon Santa Cruz, Corina Junquera, Laureano Simón, Antonio Martínez, J. Luis Gutiérrez Baños, Marta López-Brea, Clara Esparza, J. Fernando Val-Bernal
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Fibroblast growth factor receptor 3 (FGFR3) mutations have been associated with achondroplastic syndromes and urinary bladder carcinomas. Here we describe changes in FGFR3 mRNA and protein expression in transitional carcinomas and determine the effect of monoclonal antibodies against FGFR3 in RT-112 cell line proliferation. Experimental Design: We used microarray tools to evaluate FGFR3 mRNA expression in 22 urinary bladder carcinomas at different stages (noninvasive pTa, lamina propria invasive pT1, and muscular invasive pT2) and 7 nonneoplastic tissue controls. FGFR3 protein expression was evaluated by Western blotting in 15 different carcinomas and 3 nonneoplastic controls. Two hundred thirty-seven urinary bladder and renal pelvis carcinomas and 21 negative controls were tested on tissue microarrays by immunohistochemistry. The effect on cell proliferation in the RT-112 bladder cancer cell line of monoclonal antibodies against FGFR3 was also evaluated. Results: Overexpression of FGFR3 mRNA was found in pTa and pT1 stage carcinomas (fold change &amp;gt;8) and in pT2 carcinomas (fold change &amp;gt;4). Nonneoplastic urinary bladder samples do not express FGFR3 protein. However, 83% of pTa, 100% of pT1, and 50% of pT2 carcinomas expressed FGFR3 as determined by Western blotting. By immunohistochemistry, FGFR3 was positive in 71.4% of pTa, 72% of pT1, and 49.2% of pT2 cases as well as 61.5% of upper urinary tract carcinomas. Proliferation of the RT-112 cell line was inhibited with monoclonal antibodies against FGFR3. Conclusions: FGFR3 seems to play an important role in transitional cell carcinoma development. Our results suggest that FGFR3 antagonists could be developed as possible therapeutics for treatment of urinary tract carcinoma.
Ultrasensitive Measurement of Hotspot Mutations in Tumor DNA in Blood Using Error-Suppressed Multiplexed Deep Sequencing
Authors: Azeet Narayan, Nicholas J. Carriero, Scott N. Gettinger, Jeannie Kluytenaar, Kevin R. Kozak, Torunn I. Yock, Nicole E. Muscato, Pedro Ugarelli, Roy H. Decker, Abhijit A. Patel
Journal: Cancer Research (2012)

Detection of cell-free tumor DNA in the blood has offered promise as a cancer biomarker, but practical clinical implementations have been impeded by the lack of a sensitive and accurate method for quantitation that is also simple, inexpensive, and readily scalable. Here we present an approach that uses next-generation sequencing to quantify the small fraction of DNA molecules that contain tumor-specific mutations within a background of normal DNA in plasma. Using layers of sequence redundancy designed to distinguish true mutations from sequencer misreads and PCR misincorporations, we achieved a detection sensitivity of approximately 1 variant in 5,000 molecules. In addition, the attachment of modular barcode tags to the DNA fragments to be sequenced facilitated the simultaneous analysis of more than 100 patient samples. As proof-of-principle, we showed the successful use of this method to follow treatment-associated changes in circulating tumor DNA levels in patients with non-small cell lung cancer. Our findings suggest that the deep sequencing approach described here may be applied to the development of a practical diagnostic test that measures tumor-derived DNA levels in blood.
The Effect of Alpha-Tocopherol and Beta-Carotene Supplementation on COPD Symptoms
Authors: MATTI RAUTALAHTI, JARMO VIRTAMO, JARI HAUKKA, OLLI P. HEINONEN, JOUKO SUNDVALL, DEMETRIUS ALBANES, JUSSI K. HUTTUNEN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The effects of alpha-tocopherol (50 mg/d) and beta-carotene (20 mg/d) supplementation on symptoms of chronic obstructive pulmonary disease were studied among the 29,133 participants of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study undertaken to investigate the effects of these two substances in the prevention of lung and other cancers. During the follow-up the supplementations did not affect the recurrence or incidence of chronic cough, phlegm, or dyspnea. The prevalence of chronic bronchitis and dyspnea at baseline was lower among those with high dietary intake of beta-carotene (OR = 0.78 and 0.67, respectively) or vitamin E (OR = 0.87 and 0.77) and high serum beta-carotene (OR = 0.59 and 0.62) and alpha-tocopherol (OR = 0.76 and 0.82). High intake and serum levels of retinol were associated with low prevalence of dyspnea (OR = 0.84 and 0.80, respectively) but not with chronic bronchitis. The results indicate no benefit from supplementation with alpha-tocopherol or beta-carotene on the symptoms of chronic obstructive pulmonary disorders but support the beneficial effect of dietary intake of fruits and vegetables rich in these compounds.
Influenza vaccination during the first 6 months after solid organ transplantation is efficacious and safe
Authors: P. Pérez-Romero, A. Bulnes-Ramos, J. Torre-Cisneros, J. Gavaldá, T.A. Aydillo, A. Moreno, M. Montejo, M.C. Fariñas, J. Carratalá, P. Muñoz, M. Blanes, J. Fortún, A. Suárez-Benjumea, F. López-Medrano, J.L. Barranco, M. Peghin, C. Roca, R. Lara, E. Cordero, J.M. Alamo, A. Gasch, M.A. Gentil-Govantes, F.J. Molina-Ortega, E. Lage, J. Martínez-Atienza, M. Sánchez, C. Rosso, J.M. Arizón, M. Aguera, S. Cantisán, J.L. Montero, A. Páez, A. Rodríguez, S. Santos, E. Vidal, C. Berasategui, M. Campins, M. López-Meseguer, B. Saez, M.A. Marcos, G. Sanclemente, N. Diez, J. Goikoetxea, F. Casafont, M. Cobo-Beláustegy, R. Durán, E. Fábrega-García, S. Fernández-Rozas, C. González-Rico, F. Zurbano-Goñi, M. Bodro, J. Niubó, S. Oriol, N. Sabé, F. Anaya, E. Bouza, P. Catalán, P. Diez, A. Eworo, M. Kestler, P. Lopez-Roa, D. Rincón, M. Rodríguez, M. Salcedo, Y. Sousa, M. Valerio, I. Morales-Barroso, J.M. Aguado, J. Origuen
Journal: Clinical Microbiology and Infection (2015)
Rare diseases bullet 3: Wegener's granulomatosis
Authors: C. A Langford, G. S Hoffman
Journal: Thorax (1999)

Wegener’s granulomatosis (WG) is a necrotising granulomatous vasculitis which has a clinical predilection for the upper airways, lungs, and kidneys. The cause of WG remains unclear although recent investigations have begun to shed light on the immune mechanisms that may play a part in the pathophysiology of the disease. Therapeutic interventions in WG were largely ineffective until the introduction of combined treatment with cyclophosphamide and glucocorticoids which dramatically improved patient outcome. While disease relapse and drug toxicity remain of concern with this regimen, it has given us the opportunity for longer term follow up of patients from which we have gained a greater understanding of the disease.

The prevalence of WG in the United States has been estimated to be at least three per 100 000 with a male to female ratio of about 1:1. Most patients (80–97%) are Caucasian, whereas African-Americans comprise about 2–8% of most cohorts. The mean age at diagnosis is about 40–55 years, although individuals of any age may be affected.1 Whether there is significant variation in onset of disease with different seasons or precipitation of illness by inhalation of certain particulate or gaseous materials or infection remains a matter of controversy. Recent studies have not supported the notion of seasonal variation whether the data be derived from patient perceptions of disease onset, medical records, or national hospital discharge surveys.1 2 

A case-control study that compared patients with WG, healthy controls, individuals with idiopathic inflammatory pulmonary diseases and a variety of rheumatological diseases evaluated exposure to environmental particulate materials and gaseous substances.2 Over 75% of patients in all groups noted environmental exposure to inhaled materials during the year prior to onset of the diseases (or the interview date for healthy controls). The absence of a striking difference between patients with WG and control subjects, …
Molecular Mimicry and T Cell–mediated Autoimmune Disease
Authors: Vincenzo Barnaba, Francesco Sinigaglia
Journal: The Journal of Experimental Medicine (1997)

Both T cell tolerance and productive T cell responses require the interaction of the TCR with specific MHC–peptide ligands, triggering a cascade of signals that ultimately can lead to either proliferation or cell death (1– 3). These two opposing processes, which can occur during both peripheral
The dilating effect of histamine on pial arteries of cats and its mediation by H2 receptors.
Authors: M Wahl, W Kuschinsky
Journal: Circulation Research (1979)

We studied the effect of histamine and H1 or H2 blockers on the diameter of pial arteries (39-227 micron) using microapplication into the perivascular space. Concentration-response curves for histamine showed dilations which started at 10(-7) M and were maximal at 10(-5) and 10(-4) M. The H2 blocker, cimetidine, induced no vascular reaction over the whole concentration range tested (10(-7) to 10(-3) M). The H1 blocker, mepyramine, was not vasoactive in the concentration range from 10(-7) to 5 X 10(-5) M and evoked dilations at higher concentrations. The concentration-response curve for histamine was only slightly displaced by 10(-5) M mepyramine but was significantly shifted to the right by 10(-5) M cimetidine. The dilating effect of histamine could be reduced in a stepwise manner by increasing concentrations of cimetidine. These findings are in accordance with a selective antagonism between histamine and cimetidine at the H2 receptors of smooth muscle cells of pial arteries. The insignificant role of H1 receptors in histamine-induced dilations is supported by the finding that a combination of H1 and H2 blockers resulted in the same reduction of histamine-induced dilation as did the application of the H2 blocker.