tbuckley/cabot-search huggingface dataset:
Progressive dyspnoea in a 40­yr­old female
Authors: O. Ghekiere, B. Weynand, P. Collard, E. Coche
Journal: European Respiratory Journal (2003)

Case historyA 40-yr-old female presented with dyspnoea on minimal exertion and a paroxysmal dry cough, keeping her awake for long periods.The shortness of breath was reported to be progressive over the last 18 months.She had never smoked and was not on medication.There was no recent history of travelling and she only had a dog at home.Her medical history was marked with autosomal dominant polycystic kidney disease.On clinical examination, the patient presented a moderate fever measured at 39uC and a regular pulse (90 beats?min -1 ); blood pressure was 130/90 mmHg.Fine inspiratory crackles were heard on the left hemithorax and on the right base.A blood sample revealed an inflammatory syndrome with a C-reactive protein (CRP) level of 97 mg?L -1 .Arterial blood gas analysis yielded a severe arterial hypoxaemia with an arterial oxygen tension (Pa,O 2 ) of 4.26 kPa (32 mmHg) and an oxygen saturation of 62%.The results of spirography showed an important volume restriction: total lung capacity 2.55 L (normal 7.97 L); vital capacity 1.40 L (normal 6.09 L); forced expiratory volume in one second (FEV1) 1.07 (normal 4.65 L).A chest radiograph (fig. 1) was performed, followed by a high-resolution computed tomography (HRCT) scan of the chest (fig.2).The patient was treated with inhaled steroids, inhaled bronchodilatators, oxygen and antibiotics.Broad-spectrum antibiotics were given for 15 days with improvement of the inflammatory syndrome, but with no significant improvement of the dyspnoea.Due to lack of improvement with empiric therapy, surgical lung biopsy was performed on two different lobes (figs 3a and b) from the right lung.
Erythrocyte membrane phosphorylation in aging rats
Authors: Raj Kumar
Journal: American Journal of Hematology (1985)

Abstract By sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), the protein profile and autophosphorylation of plasma membranes of red cells from 3‐, 9‐, 18‐, and 30‐month‐old rats was examined. No major changes in SDS‐PAGE protein profiles were noticeable. However, endogenous (auto) and exogenous phosphorylation in the presence of (γ− 32 P)ATP showed an age‐dependent increase in 32 P utake. pH optimum was between 8.0 and 9.0 for all age groups. Cyclic AMP was without effect on either endogenous or exogenous phosphorylation. Further analysis of the autophosphorylation reaction by quantification of autoradiograms obtained from SDS‐PAGE gels displayed an age‐dependent increase in phosphorylation of bands 2, 3, 4.1, and 4.5 [nomenclature of Fairbanks et al. Biochemistry 10:2606, 1971] and of several other minor bands. The data imply that alteration in red cell membranes may occur during aging of rats causing an enhancement in endogenous kinase activity and possibly in the number of phosphate acceptor sites as well.
H<scp>UMAN</scp> N<scp>EURODEGENERATIVE</scp> D<scp>ISEASE</scp> M<scp>ODELING</scp> U<scp>SING</scp> <i>D<scp>ROSOPHILA</scp></i>
Authors: Nancy M. Bonini, Mark E. Fortini
Journal: Annual Review of Neuroscience (2003)

▪ Abstract A number of approaches have been taken to recreate and to study the role of genes associated with human neurodegenerative diseases in the model organism Drosophila. These studies encompass the polyglutamine diseases, Parkinson's disease, Alzheimer's disease, and tau-associated pathologies. The findings highlight Drosophila as an important model system in which to study the fundamental pathways influenced by these genes and have led to new insights into aspects of pathogenesis and modifier mechanisms.
Body mass index is associated with the development of acute respiratory distress syndrome
Authors: M N Gong, E K Bajwa, B T Thompson, D C Christiani
Journal: Thorax (2009)

<h3>Background:</h3> The relationship between body mass index (BMI) and development of acute respiratory distress syndrome (ARDS) is unknown. <h3>Methods:</h3> A cohort study of critically ill patients at risk for ARDS was carried out. BMI was calculated from admission height and weight. Patients were screened daily for AECC (American European Consensus Committee)-defined ARDS and 60-day ARDS mortality. <h3>Results:</h3> Of 1795 patients, 83 (5%) patients were underweight (BMI &lt;18.5 kg/m<sup>2</sup>), 627 (35%) normal (BMI 18.5–24.9), 605 (34%) overweight (BMI 25–29.9), 364 (20%) obese (BMI 30–39.9) and 116 (6%) severely obese (BMI ⩾40). Increasing weight was associated with younger age (p&lt;0.001), diabetes (p&lt;0.0001), higher blood glucose (p&lt;0.0001), lower prevalence of direct pulmonary injury (p&lt;0.0001) and later development of ARDS (p = 0.01). BMI was associated with ARDS on multivariate analysis (OR<sub>adj</sub> 1.24 per SD increase; 95% CI 1.11 to 1.39). Similarly, obesity was associated with ARDS compared with normal weight (OR<sub>adj</sub> 1.66; 95% CI 1.21 to 2.28 for obese; OR<sub>adj</sub> 1.78; 95% CI 1.12 to 2.92 for severely obese). Exploratory analysis in a subgroup of intubated patients without ARDS on admission (n = 1045) found that obese patients received higher peak (p&lt;0.0001) and positive end-expiratory pressures (p&lt;0.0001) than non-obese patients. Among patients with ARDS, increasing BMI was associated with increased length of stay (p = 0.007) but not with mortality (OR<sub>adj</sub> 0.89 per SD increase; 95% CI 0.71 to 1.12). <h3>Conclusion:</h3> BMI was associated with increased risk of ARDS in a weight-dependent manner and with increased length of stay, but not with mortality. Additional studies are needed to determine whether differences in initial ventilator settings may contribute to ARDS development in the obese.
Mechanisms of Acute Eosinophil Mobilization from the Bone Marrow Stimulated by Interleukin 5: The Role of Specific Adhesion Molecules and Phosphatidylinositol 3-Kinase
Authors: Roger T. Palframan, Paul D. Collins, Nicholas J. Severs, Stephen Rothery, Timothy J. Williams, Sara M. Rankin
Journal: The Journal of Experimental Medicine (1998)

Mobilization of bone marrow eosinophils is a critical early step in their trafficking to the lung during allergic inflammatory reactions. We have shown previously that the cytokine interleukin (IL)-5, generated during an allergic inflammatory reaction in the guinea pig, acts systemically to mobilize eosinophils from the bone marrow. Here, we have investigated the mechanisms underlying this release process. Examination by light and electron microscopy revealed the rapid migration of eosinophils from the hematopoietic compartment and across the bone marrow sinus endothelium in response to IL-5. Using an in situ perfusion system of the guinea pig hind limb, we showed that IL-5 stimulated a dose-dependent selective release of eosinophils from the bone marrow. Eosinophils released from the bone marrow in response to IL-5 expressed increased levels of β2 integrin and a decrease in L-selectin, but no change in α4 integrin levels. A β2 integrin–blocking antibody markedly inhibited the mobilization of eosinophils from the bone marrow stimulated by IL-5. In contrast, an α4 integrin blocking antibody increased the rate of eosinophil mobilization induced by IL-5. In vitro we demonstrated that IL-5 stimulates the selective chemokinesis of bone marrow eosinophils, a process markedly inhibited by two structurally distinct inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. Wortmannin was also shown to block eosinophil release induced by IL-5 in the perfused bone marrow system. The parallel observations on the bone marrow eosinophil release process and responses in isolated eosinophils in vitro suggest that eosinophil chemokinesis is the driving force for release in vivo and that this release process is regulated by α4 and β2 integrins acting in opposite directions.
Novel Transcriptome Patterns Accompany Evolutionary Restoration of Defective Social Development in the Bacterium Myxococcus xanthus
Authors: Supriya V Kadam, Sigrun Wegener-Feldbrügge, Lotte Søgaard-Andersen, Gregory J Velicer
Journal: Molecular Biology and Evolution (2008)

Evolutionary trait losses can be restored by direct reversion or by compensatory pathways. Upon starvation, the bacterium Myxococcus xanthus develops into spore-bearing fruiting bodies, but this ability can be rapidly lost during evolution. Some developmentally defective strains of M. xanthus "cheat" on proficient strains during development by superior sporulation in mixed cultures. Here, we examine transcriptomic patterns accompanying the evolution of a cheater (obligate cheater [OC]) to a developmentally competent strain (PX) by a single mutation. Using quantitative real-time-polymerase chain reaction analysis of 5 genes essential for development, we initially show that restoration of development in strain PX was associated with increased expression of 4 of these genes, not only relative to OC but also relative to the developmentally proficient ancestor of both OC and PX (wild type [WT]). Global transcriptome analyses showed further that developmental expression of well more than 100 genes differ significantly between PX and the proficient WT ancestor. Moreover, the expression profile of PX was found to differ from that of WT more than does that of the defective intermediate strain OC. These results show that the restoration of a complex trait is accompanied by novel expression patterns across a large number and wide variety of genes, rather than by a large-scale return to ancestral expression patterns.
Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis
Authors: T McWilliams, A U Wells, A C Harrison, S Lindstrom, R J Cameron, E Foskin
Journal: Thorax (2002)

<b>Background:</b> Previous studies suggest that bronchoscopy and a single induced sputum sample are equally effective for diagnosing pulmonary tuberculosis. <b>Methods:</b> In a prospective study of subjects with possibly active pulmonary tuberculosis, the diagnostic yield of three induced sputum tests was compared with that of bronchoscopy. Subjects either produced no sputum or (acid fast) smear negative sputum. Bronchoscopy was only performed if at least two induced sputum samples were smear negative. <b>Results:</b> Of 129 subjects who completed all tests, 27 (21%) had smear negative and culture positive specimens, 14 (52%) on bronchoscopy and 26 (96%) on induced sputum (p&lt;0.005). One patient was culture positive on bronchoscopy alone compared with 13 on induced sputum alone; 13 were culture positive on both tests. Induced sputum positivity was strikingly more prevalent when chest radiographic appearances showed any features of active tuberculosis (20/63, 32%) than when appearances suggested inactivity (1/44, 2%; p&lt;0.005). Induced sputum costs were about one third those of bronchoscopy, and the ratio of costs of the two tests per case of tuberculosis diagnosed could be as much as 1:6. <b>Conclusions:</b> In subjects investigated for possibly active or inactive tuberculosis who produce no sputum or have smear negative sputum, the most cost effective strategy is to perform three induced sputum tests without bronchoscopy. Induced sputum testing carries a high risk of nosocomial tuberculosis unless performed in respiratory isolation conditions. The cost benefits shown could be lost if risk management measures are not observed.
Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas
Authors: V. Gebbia, F. Verderame, F. Ferraù, R. Bordonaro, A. Callari, M. Caruso, M.L. Tirrito, R. Valenza, G. Cicero, N. Borsellino, P. Tralongo
Journal: Annals of Oncology (2006)
Hepatic stellate cells relay inflammation signaling from sinusoids to parenchyma in mouse models of immune‐mediated hepatitis
Authors: Tomoko Fujita, Kitipong Soontrapa, Yoshiya Ito, Keiko Iwaisako, Catharina Sagita Moniaga, Masataka Asagiri, Masataka Majima, Shuh Narumiya
Journal: Hepatology (2015)

Hepatic stellate cells (HSCs) constitute the liver sinusoid with Kupffer cells and liver sinusoidal endothelial cells. While the sinusoid functions as the gateway to liver inflammation, whether HSCs contribute to liver inflammation and, if so, how they exert such functions remain elusive. Here, we found that mouse as well as human HSCs expressed DP1 receptor for prostaglandin D 2 selectively in the liver. Pharmacological stimulation of DP1 by BW245C, a DP1‐selective agonist, suppressed the activation of cultured HSCs by tumor necrosis factor‐α at least in part through down‐regulation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling and inhibition of c‐Jun N‐terminal kinase phosphorylation. DP1 deficiency or BW245C administration in mice significantly enhanced or suppressed concanavalin A (ConA)–induced hepatitis, respectively. ConA injection induced tumor necrosis factor‐α and interferon‐γ expression in the sinusoid, which was suppressed by administration of BW245C. Coculture of spleen cells and liver nonparenchymal cells showed that ConA first activated spleen cells and that this activation led to activation of nonparenchymal cells to secondarily produce tumor necrosis factor‐α and interferon‐γ. Microarray analysis revealed ConA‐induced expression of endothelin‐1, tissue factor, and chemokines in the liver and inducible nitric oxide synthase in hepatocytes, resulting in flow stagnation, leukocyte adherence and migration to the parenchyma, and hepatocyte death. DP1 stimulation inhibits all these events in the liver. Therefore, HSCs mediate amplification of ConA‐induced liver inflammation in the sinusoid, causing direct and indirect hepatocyte injury, and DP1 stimulation inhibits this HSC activation. Conclusions : HSCs integrate cytokine‐mediated inflammatory responses in the sinusoids and relay them to the liver parenchyma, and these HSC actions are inhibited by DP1 stimulation. (H epatology 2016;63:1325–1339)
Reply to S. Hapani et al
Authors: Gary H. Lyman, Herbert I. Hurwitz, Florin Sirzén, Ulrich-Peter Rohr
Journal: Journal of Clinical Oncology (2011)

read the article by Hurwitz et al 1 on the venous thromboembolic events (VTEs) with chemotherapy plus bevacizumab in patients with cancer that was based on a meta-analysis of individual patient data with great interest.We would like to make three comments that are relevant to the conclusion of the study, which is not consistent with our previous analysis. 2 First, the overall conclusion of bevacizumab's effect on VTEs depends on the studies included for the meta-analysis.This study included 10 randomized controlled clinical trials, which may be a small fraction of total bevacizumab trials.The article did not mention how many studies the authors had screened before the final selection of these trials.The difference in the number of included trials between this study and our previous meta-analysis 2 is substantial; although the two meta-analyses shared the same eight studies, they differed in a total of nine trials; the current study had added two new studies by Miles et al 3 and Van Cutsem et al 4 with a calculated summary risk ratio of 0.82 (95% CI, 0.60 to 1.11) and did not have seven other trials with asummaryrelativeriskof1.27(95%CI,0.94to1.73)whichwereincluded in our study. 2Thus, the determination of overall RR by this study will be most likely underestimated by the addition and exclusion of these studies.Second, the exposure-adjusted incidence as rate per 100 patientyears according to progression-free survival to estimate the risk may introduce a bias of underestimation.This is based on the assumption that these VTEs occurred evenly over time and were directly proportional to the duration.As shown in the Kaplan-Meier analysis in Figure 3 of the article, 1 the events tend to occur early after the drug therapy.In addition, as reported in the article, the median time to VTE was 2.2 months for the bevacizumab group and 1.7 months for the control group, which suggests the events did not occur equally over the exposure time.Third, retrospective studies tend to substantially underestimate the incidence of VTEs as a result of insufficient and irregular detection.To fully and accurately understand the effect of bevacizumab on the risk of VTEs, it would be ideal to perform a randomized controlled trial with a primary end point of VTEs measured prospectively and regularly.
Cinaciguat (BAY 58–2667) Improves Cardiopulmonary Hemodynamics in Patients With Acute Decompensated Heart Failure
Authors: Harald Lapp, Veselin Mitrovic, Norbert Franz, Hubertus Heuer, Michael Buerke, Judith Wolfertz, Wolfgang Mueck, Sigrun Unger, Georg Wensing, Reiner Frey
Journal: Circulation (2009)

Cinaciguat (BAY 58-2667) is the first of a new class of soluble guanylate cyclase activators in clinical development for acute decompensated heart failure. We aimed to assess the hemodynamic effects, safety, and tolerability of intravenous cinaciguat in patients with acute decompensated heart failure (pulmonary capillary wedge pressure > or =18 mm Hg).After initial dose finding (part A; n=27), cinaciguat was evaluated in the nonrandomized, uncontrolled proof-of-concept part of the study (part B; n=33) using a starting dose of 100 microg/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by > or =4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 microg/h (n=2), 200 microg/h (n=12), and 400 microg/h (n=16). Compared with baseline, a 6-hour infusion of cinaciguat led to significant reductions in pulmonary capillary wedge pressure (-7.9 mm Hg), mean right atrial pressure (-2.9 mm Hg), mean pulmonary artery pressure (-6.5 mm Hg), pulmonary vascular resistance (-43.4 dynes . s . cm(-5)), and systemic vascular resistance (-597 dynes . s . cm(-5)), while increasing heart rate by 4.4 bpm and cardiac output by 1.68 L/min. The responder rate was 53% after 2 hours, 83% after 4 hours, and 90% after 6 hours. Cinaciguat was well tolerated, with 13 of 60 patients reporting 14 drug-related treatment-emergent adverse events of mild to moderate intensity, most commonly hypotension.Cinaciguat has potent preload- and afterload-reducing effects, increasing cardiac output. Further investigation of cinaciguat for acute decompensated heart failure is warranted.
Physical mapping of genes in somatic cell radiation hybrids by comparative genomic hybridization to cDNA microarrays
Authors: Johann Y Lin, Jonathan R Pollack, Fan-Li Chou, Christian A Rees, Allen T Christian, Joel S Bedford, Patrick O Brown, Mark H Ginsberg
Journal: Genome biology (2002)

Somatic cell mutants can be informative in the analysis of a wide variety of cellular processes. The use of map-based positional cloning strategies in somatic cell hybrids to analyze genes responsible for recessive mutant phenotypes is often tedious, however, and remains a major obstacle in somatic cell genetics. To fulfill the need for more efficient gene mapping in somatic cell mutants, we have developed a new DNA microarray comparative genomic hybridization (array-CGH) method that can rapidly and efficiently map the physical location of genes complementing somatic cell mutants to a small candidate genomic region. Here we report experiments that establish the validity and efficacy of the methodology. CHO cells deficient for hypoxanthine:guanine phosphoribosyl transferase (HPRT) were fused with irradiated normal human fibroblasts and subjected to HAT selection. Cy5-labeled genomic DNA from the surviving hybrids containing the HPRT gene was mixed with Cy3-labeled genomic DNA from normal CHO cells and hybridized to a microarray containing 40,185 cDNAs, representing 29,399 genes (UniGene clusters). The DNA spots with the highest Cy5:Cy3 fluorescence ratios corresponded to a group of genes mapping within a 1 Mb interval centered near position 142.7 Mb on the X chromosome, the genomic location of HPRT. The results indicate that our physical mapping method based on radiation hybrids and array-CGH should significantly enhance the speed and efficiency of positional cloning in somatic cell genetics.
Combination of vemurafenib and cobimetinib in patients with advanced BRAFV600-mutated melanoma: a phase 1b study
Authors: Antoni Ribas, Rene Gonzalez, Anna Pavlick, Omid Hamid, Thomas F Gajewski, Adil Daud, Lawrence Flaherty, Theodore Logan, Bartosz Chmielowski, Karl Lewis, Damien Kee, Peter Boasberg, Ming Yin, Iris Chan, Luna Musib, Nicholas Choong, Igor Puzanov, Grant A McArthur
Journal: The Lancet Oncology (2014)
Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1
Authors: Emily R. Eden, Dilipkumar D. Patel, Xi-Ming Sun, Jemima J. Burden, Michael Themis, Matthew Edwards, Philip Lee, Clare Neuwirth, Rossitza P. Naoumova, Anne K. Soutar
Journal: Journal of Clinical Investigation (2002)

Familial hypercholesterolemia is an autosomal dominant disorder with a gene-dosage effect that is usually caused by mutations in the LDL receptor gene that disrupt normal clearance of LDL. In the homozygous form, it results in a distinctive clinical phenotype, characterized by inherited hypercholesterolemia, cholesterol deposition in tendons, and severe premature coronary disease. We described previously two families with autosomal recessive hypercholesterolemia that is not due to mutations in the LDL receptor gene but is characterized by defective LDL receptor-dependent internalization and degradation of LDL by transformed lymphocytes from the patients. We mapped the defective gene to chromosome 1p36 and now show that the disorder in these and a third English family is due to novel mutations in ARH1, a newly identified gene encoding an adaptor-like protein. Cultured skin fibroblasts from affected individuals exhibit normal LDL receptor activity, but their monocyte-derived macrophages are similar to transformed lymphocytes, being unable to internalize and degrade LDL. Retroviral expression of normal human ARH1 restores LDL receptor internalization in transformed lymphocytes from an affected individual, as demonstrated by uptake and degradation of (125)I-labeled LDL and confocal microscopy of cells labeled with anti-LDL-receptor Ab.
Thirty-Day Hospital Readmission Following Discharge From Postacute Rehabilitation in Fee-for-Service Medicare Patients
Authors: Kenneth J. Ottenbacher, Amol Karmarkar, James E. Graham, Yong-Fang Kuo, Anne Deutsch, Timothy A. Reistetter, Soham Al Snih, Carl V. Granger
Journal: JAMA (2014)

The Centers for Medicare & Medicaid Services recently identified 30-day readmission after discharge from inpatient rehabilitation facilities as a national quality indicator. Research is needed to determine the rates and factors related to readmission in this patient population.