tbuckley/cabot-search huggingface dataset:
Genomic analysis reveals key aspects of prokaryotic symbiosis in the phototrophic consortium “Chlorochromatium aggregatum”
Authors: Zhenfeng Liu, Johannes Müller, Tao Li, Richard M Alvey, Kajetan Vogl, Niels-Ulrik Frigaard, Nathan C Rockwell, Eric S Boyd, Lynn P Tomsho, Stephan C Schuster, Petra Henke, Manfred Rohde, Jörg Overmann, Donald A Bryant
Journal: Genome biology (2013)

'Chlorochromatium aggregatum' is a phototrophic consortium, a symbiosis that may represent the highest degree of mutual interdependence between two unrelated bacteria not associated with a eukaryotic host. 'Chlorochromatium aggregatum' is a motile, barrel-shaped aggregate formed from a single cell of 'Candidatus Symbiobacter mobilis", a polarly flagellated, non-pigmented, heterotrophic bacterium, which is surrounded by approximately 15 epibiont cells of Chlorobium chlorochromatii, a non-motile photolithoautotrophic green sulfur bacterium. We analyzed the complete genome sequences of both organisms to understand the basis for this symbiosis. Chl. chlorochromatii has acquired relatively few symbiosis-specific genes; most acquired genes are predicted to modify the cell wall or function in cell-cell adhesion. In striking contrast, 'Ca. S. mobilis' appears to have undergone massive gene loss, is probably no longer capable of independent growth, and thus may only reproduce when consortia divide. A detailed model for the energetic and metabolic bases of the dependency of 'Ca. S. mobilis' on Chl. chlorochromatii is described. Genomic analyses suggest that three types of interactions lead to a highly sophisticated relationship between these two organisms. Firstly, extensive metabolic exchange, involving carbon, nitrogen, and sulfur sources as well as vitamins, occurs from the epibiont to the central bacterium. Secondly, 'Ca. S. mobilis' can sense and move towards light and sulfide, resources that only directly benefit the epibiont. Thirdly, electron cycling mechanisms, particularly those mediated by quinones and potentially involving shared protonmotive force, could provide an important basis for energy exchange in this and other symbiotic relationships.
Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial
Authors: Beatriz Grinsztejn, Bach-Yen Nguyen, Christine Katlama, Jose M Gatell, Adriano Lazzarin, Daniel Vittecoq, Charles J Gonzalez, Joshua Chen, Charlotte M Harvey, Robin D Isaacs
Journal: The Lancet (2007)
The effects of zenarestat, an aldose reductase inhibitor, on peripheral neuropathy in Zucker diabetic fatty rats
Authors: Yukinori Shimoshige, Kyoko Ikuma, Tadashi Yamamoto, Shoji Takakura, Ikuo Kawamura, Jiro Seki, Seitaro Mutoh, Toshio Goto
Journal: Metabolism (2000)
Tumor Sclerosis but Not Cell Proliferation or Malignancy Grade Is a Prognostic Marker in Advanced-Stage Follicular Lymphoma: The German Low Grade Lymphoma Study Group
Authors: Wolfram Klapper, Eva Hoster, Lars Rölver, Carsten Schrader, Dirk Janssen, Markus Tiemann, Heinz-Wolfram Bernd, Olaf Determann, Martin-Leo Hansmann, Peter Möller, Alfred Feller, Harald Stein, Hans-Heinrich Wacker, Martin Dreyling, Michael Unterhalt, Wolfgang Hiddemann, German Ott
Journal: Journal of Clinical Oncology (2007)

Follicular lymphoma is an indolent lymphoma with a long median overall survival. However, a considerable number of patients die within the first 2 years after the onset of the disease. Because the treatment options vary with respect to antitumor effect and potential toxic adverse effects, the identification of high-risk patients would be helpful in directing therapeutic decisions in individual patients. Several histopathologic biomarkers for risk stratification have been suggested, but most markers have not been validated in patients treated in prospective trials.We report a comprehensive approach to evaluate histopathologic biomarkers, including WHO grade, histology, and proliferation and quantitation of immune bystander cells, in 158 patients with nodal advanced-stage follicular lymphoma treated first line within a randomized trial.Tumor sclerosis was a significant prognostic marker of poor overall survival that was independent of the Follicular Lymphoma International Prognostic Index (FLIPI). WHO grade, proliferation, and total T-cell or macrophage content were not associated with overall survival.The presence of sclerosis within the lymphoma is a marker of poor overall survival that is independent of the FLIPI. The quantification of macrophage or absolute T-cell content, grading, and proliferation are of no help in predicting the outcome of FL. Future studies need to identify surrogate markers for the prognostic immune signatures identified by gene expression profiling. Most importantly, new prognostic markers need to be confirmed in patients treated within prospective trials.
PMO-025 Three-year review of local hepato-pancreatobiliary (HPB) cancer service &amp; its impact on cancer detection in a non-tertiary centre in Mersey Region: Abstract PMO-025 Table 1
Authors: K Clark, A Boon, R Faizallah, A Singhal
Journal: Gut (2012)

<h3>Introduction</h3> Patients with HPB cancer pose complex clinical problems requiring close liaison between primary, secondary &amp; tertiary care. Reconfiguration of cancer services in the Mersey region has lead to standardisation of care for HPB cancer patients via referral to Regional Specialist Centres (RSC). However local cancer care remained fragmented and limited by the variable expertise of the respective clinical teams involved. Therefore we developed a local HPB Cancer Service (HPBCS) and hereby report 3-year impact of this service on overall patient care and cancer detection rates outside tertiary referral centres. <h3>Methods</h3> The HPBCS was launched on the Wirral in June 2008, the first such service in a large district general hospital (catchment population of 360 000) in the Mersey region. All patients with suspected HPB cancer were referred to the local HPB Team comprising of two HPB consultants and a specialist nurse. Patients are identified via 2-week referrals from primary care, acute admissions, ward referrals and radiology flags—a new concept that year upon year provides a valuable resource to the service. All patients are managed as per the Mersey &amp; Cheshire Cancer Network protocol with discussion at the appropriate RSC MDT meetings. The team meets weekly to discuss all new referrals, MDT outcomes and any sick patients. In addition to the consultant clinics, there is weekly HPB nurse-led outpatient &amp; telephone clinics that provides urgent feedback of tertiary MDT decisions, rapid access for symptom control and ensures continuity of care. <h3>Results</h3> There is a sharp increase in the HPB cancer detection and referral rates since establishing the local HPBCS which has sustained over 3-year period as summarised in Abstract PMO-025 table 1. <h3>Conclusion</h3> Since commencement of local HPBCS, there is sustained increase in number of suspected HPB cancers identified within the trust. These are referred on to the regional MDTs within 2 weeks, leading to timely and uniform care as per regional network guidelines with local ownership of care. Service was formally praised in MCCN peer review in 2010 and awarded Wirral Trust Foundation Award in 2011. There is small but consistent rise in detection of liver lesions which may reflect increasing incidence of chronic liver diseases nationally. Ever increasing pool of surveillance patients &amp; radiology alerts contribute to significant ongoing work load. <h3>Competing interests</h3> None declared.
The "hygiene hypothesis" revisited
Authors: J R Hurst
Journal: Thorax (2004)

▴ Benn CS, Melbye M, Wohlfahrt J, et al . Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life. BMJ2004;328:1223–7 [OpenUrl][1][Abstract/FREE Full Text][2] ▴ Tulic MK, Fiset P-O, Manoukian JJ, et al . Role of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasal mucosa of atopic children but not adults. Lancet2004;363:1689–97 [OpenUrl][3][CrossRef][4][PubMed][5][Web of Science][6] The “hygiene hypothesis” suggests that decreasing exposure to micro-organisms during infancy is responsible for the increasing prevalence of atopy. However, while a decreased risk of atopic disease is associated with various surrogate markers of microbial exposure including early attendance at day care, a greater number of siblings and living on a farm, specific associations between clinical episodes of infection and atopy remain ill defined and the possible mechanisms obscure. Two recent papers have sought to characterise further the links between infection and atopy. At … [1]: {openurl}?query=rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.38069.512245.FE%26rft_id%253Dinfo%253Apmid%252F15121716%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=328/7450/1223&atom=%2Fthoraxjnl%2F59%2F8%2F698.atom [3]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DTulic%26rft.auinit1%253DM.%2BK.%26rft.volume%253D363%26rft.issue%253D9422%26rft.spage%253D1689%26rft.epage%253D1697%26rft.atitle%253DRole%2Bof%2Btoll-like%2Breceptor%2B4%2Bin%2Bprotection%2Bby%2Bbacterial%2Blipopolysaccharide%2Bin%2Bthe%2Bnasal%2Bmucosa%2Bof%2Batopic%2Bchildren%2Bbut%2Bnot%2Badults.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252804%252916253-3%26rft_id%253Dinfo%253Apmid%252F15158630%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [4]: /lookup/external-ref?access_num=10.1016/S0140-6736(04)16253-3&link_type=DOI [5]: /lookup/external-ref?access_num=15158630&link_type=MED&atom=%2Fthoraxjnl%2F59%2F8%2F698.atom [6]: /lookup/external-ref?access_num=000221546300009&link_type=ISI
Neuroprotection by Gene Therapy Targeting Mutant SOD1 in Individual Pools of Motor Neurons Does not Translate Into Therapeutic Benefit in fALS Mice
Authors: Chris Towne, Veronica Setola, Bernard L Schneider, Patrick Aebischer
Journal: Molecular Therapy (2010)

A major challenge in neurological gene therapy is delivery of the transgene to sufficient cell numbers in an atraumatic manner. This is particularly difficult for motor neuron (MN) diseases that have cells located across the entire spinal cord, brain stem, and cortex. We have used the familial mouse model of amyotrophic lateral sclerosis (ALS) to examine the feasibility of body-wide intramuscular injections of adeno-associated virus serotype 6 (AAV6), a vector capable of axonal retrograde transport, to deliver therapeutic genetic information across the lower MN axis. Neonatal muscle delivery of AAV expressing small hairpin RNAs (shRNAs) against the toxic transgene in this model, human mutant superoxide dismutase 1 (mSOD1), led to significant mSOD1 knockdown in the muscle as well as innervating MNs. This knockdown conferred neuroprotection and halted muscle atrophy in individually targeted MN pools. However, despite the vector being targeted to MNs that innervate muscle groups controlling eating, breathing, and locomotion, this approach was unable to therapeutically impact on disease progression in the ALS mouse model. These results stress the complexity of gene delivery for mSOD1 silencing and suggest that critical thresholds of protein knockdown and transduction across various cell types are required to translate local neuroprotective effects into functional improvements.
Angry breathing: a prospective study of hostility and lung function in the Normative Aging Study
Authors: L D Kubzansky
Journal: Thorax (2006)

<b>Background:</b> Hostility and anger are risk factors for, or co-occur with, many health problems of older adults such as cardiovascular diseases, all-cause mortality, and asthma. Evidence that negative emotions are associated with chronic airways obstruction suggests a possible role for hostility in the maintenance and decline of pulmonary function. This study tests the hypothesis that hostility contributes to a faster rate of decline in lung function in older adults. <b>Methods:</b> A prospective examination was undertaken of the effect of hostility on change in lung function over time. Data are from the VA Normative Aging Study, an ongoing cohort of older men. Hostility was measured in 1986 in 670 men who also had an average of three pulmonary function examinations obtained over an average of 8.2 years of follow up. Hostility was ascertained using the 50-item MMPI based Cook-Medley Hostility Scale. Pulmonary function was assessed using spirometric tests to obtain measures of forced expiratory volume in 1 second (FEV<sub>1</sub>) and forced vital capacity (FVC). <b>Results:</b> Baseline pulmonary function differed between high and medium/low hostility groups (mean (SE) percent predicted FEV<sub>1</sub> 88.9 (18.5) <i>v</i> 95.3 (16.9) and FVC 92.5 (16.5) <i>v</i> 98.9 (15.9), respectively; p&lt;0.01 for both). This overall association between higher hostility and reduced lung function remained significant after adjusting for smoking and education, although the effect size was attenuated for both FEV<sub>1</sub> and FVC. Higher hostility was associated with a more rapid decline in lung function, and this effect was unchanged and remained significant for FEV<sub>1 </sub>in multivariate models but was attenuated for FVC. Each standard deviation increase in hostility was associated with a loss in FEV<sub>1</sub> of approximately 9 ml/year. <b>Conclusions:</b> This study is one of the first to show prospectively that hostility is associated with poorer pulmonary function and more rapid rates of decline among older men.
Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells
Authors: A. Gerber, A. Heimburg, A. Reisenauer, A. Wille, T. Welte, F. Bühling
Journal: European Respiratory Journal (2004)

Proteasome inhibition has become a target for antitumour and anti-inflammatory therapy. The present study investigated the influence of cysteine proteinase and proteasome inhibitors on chemokine production in lung epithelial cells and monocytic cells. The lung carcinoma cell lines A549, SK-MES, NCI-H727, virus-transformed bronchial epithelial cell line BEAS-2B, primary lung epithelial cells, and the acute monocytic leukaemia cell lines Mono-Mac-6 and THP-1 were incubated with proteasome (N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN), beta-lactone) or cysteine proteinase inhibitor (L-trans-Epoxysuccinyl-Leu-3-methylbutylamide-ethyl ester) and the influence on chemokine production (interleukin-8: IL-8, monocyte chemoattractant protein-1, RANTES) was quantified at protein and mRNA levels. Inhibition of proteasome activity by ALLN and beta-lactone resulted in significantly increased IL-8 secretion (5- to 22-fold). Cysteine proteinase inhibitors did not influence chemokine production. The simultaneous rise in IL-8 mRNA was caused by an increased half-life of mRNA and increased RNA synthesis. Moreover, analysis of transcription factor activation revealed induction of activator protein-1 (c-Jun) activity by proteasome inhibition, whereas nuclear factor-kappaB (p50 and p65) was not activated. The significant increase in IL-8 production after proteasome inhibition was also observed in primary lung epithelial cells and in monocytic cells. In addition, the secreted IL-8 was biologically active as shown by the neutrophil chemotaxis assay. In conclusion, it was shown that proteasome inhibitors stimulate interleukin-8 secretion in lung epithelial cells and monocytic cells, thus recruiting neutrophils.
Expiratory flow limitation in awake sleep-disordered breathing subjects
Authors: G. Liistro, C Veriter, M Dury, G Aubert, D Stanescu
Journal: European Respiratory Journal (1999)

Increased upper airways (UA) collapsibility has been implicated in the pathogeny of sleep-disordered breathing (SDB). An increased UA instability during expiration has recently been shown in healthy subjects. The present study assessed UA collapsibility in SDB patients by applying negative pressure during expiration. Full-night polysomnography was performed in 16 subjects (all snorers) with a wide range of SDB, and in six healthy control subjects. Physical examination, spirometry, and maximal inspiratory and expiratory flow rates were within normal limits for all 22 subjects. Negative expiratory pressure (NEP) (-5 cmH2O) was applied during quiet breathing in seated and supine position. Flow limitation (FL) during NEP was expressed as the percentage of tidal volume during which expiratory flow was less than or equal to the flow recorded during quiet breathing (%FL). The mean desaturation index (DI) of the 16 subjects was 27.3+/-26.4 (+/-sD) and the average FL in supine position was 38.4+/-37.9%. A close correlation between %FL supine during wakefulness and DI during sleep (r=0.84, p&lt;0.001) was found. All obstructive sleep apnoea subjects had &gt;30%FL supine. There was no FL in the six control subjects. In conclusion, negative expiratory pressure application during expiration appears to be a useful, noninvasive method for the evaluation of subjects with sleep-disordered breathing. Present results suggest that upper airway collapsibility can be detected in these subjects during wakefulness.
The reticular point of view in dermatoscopy
Authors: Vincenzo Panasiti, Valeria Devirgiliis, Michela Curzio, Vincenzo Roberti, Silvia Gobbi, Raffaele Masciangelo, Benedetto Mastrecchia, Stefano Calvieri, Ugo Bottoni
Journal: Journal of the American Academy of Dermatology (2009)
Fatty liver in chronic hepatitis C infection: unravelling the mechanisms
Authors: J. A Oben, E. Paulon
Journal: Gut (2007)

A step closer to understanding fatty liver due to HCV

Chronic hepatitis C virus (HCV) infection afflicts about 200 million people worldwide and is presently the most common cause of cirrhosis and hepatocellular carcinoma in Western countries. Over the last decade, an association between HCV infection, hepatic steatosis, insulin resistance (IR) and type II diabetes has been highlighted, although the cause–effect relationship underlying the co-existence of these phenomena has yet to be completely clarified.1 These observations are important because the presence of steatosis and/or IR in chronic HCV infection appears to modulate the progression of fibrosis and the response to antiviral therapy in chronic HCV infection.2–4

Mechanisms underling steatosis development in chronic HCV infection have been demonstrated to be genotype specific, with an apparent direct steatogenic effect of genotype 3, and an IR-associated steatosis effect exerted by genotype 1.5,6 The direct steatogenic effect of HCV genotype 3 is confirmed by findings such as those showing a correlation between HCV genotype 3 RNA level and steatosis in chronically infected patients and the resolution of steatosis in genotype 3-infected patients after response to antiviral treatment.5–7

Several mechanisms whereby HCV infection can directly cause steatosis have been described. HCV can affect de novo fatty acid biosynthesis, triglyceride (TG) assembly and secretion, and lipid peroxidation. HCV core protein has also been shown to localise in the periphery of TG-rich lipid droplets and on the cytosolic surface of the endoplasmic reticulum (ER) membrane, and it might physically interfere with lipids and other proteins involved in very low-density lipoprotein (VLDL) assembly.8 Lipid secretion can be altered by the effect of HCV on microsomal triglyceride transfer protein (MTP) and apolipoproteins. MTP is an enzyme that regulates VLDL assembly and its activity is impaired by HCV core protein in core-transgenic …
Myocardial Infarction and Rheumatoid Arthritis
Authors: Robert L. Swezey
Journal: JAMA (1970)

To the Editor.—  The paper of Irving Karten, MD ( 210 :1717, 1969), reports on 102 consecutive admissions of patients with rheumatoid arthritis in six of whom diffuse vasculitis was present. Two of his patients developed myocardial infarctions, and one came to autopsy with confirmation of coronary arteritis as the cause of the myocardial infarction. This was also suspected in the second patient who survived.  Dr. Karten then reviewed 95 autopsy patients with rheumatoid arthritis at the Goldwater Memorial Hospital and found seven who had myocardial infarctions. None of these showed any evidence of coronary arteritis in the available histological sections.  In my report on myocardial infarction due to rheumatoid arteritis ( 199 :855, 1967), my review of the literature at that time suggested that of those patients with rheumatoid arthritis and myocardial infarctions who had come to autopsy, the majority had rheumatoid arteritis as the basis for the infarction. In my
Identification and validation of genes affecting aortic lesions in mice
Authors: Xia Yang, Larry Peterson, Rolf Thieringer, Joshua L. Deignan, Xuping Wang, Jun Zhu, Susanna Wang, Hua Zhong, Serguei Stepaniants, John Beaulaurier, I-Ming Wang, Ray Rosa, Anne-Marie Cumiskey, Jane Ming-Juan Luo, Qi Luo, Kashmira Shah, Jianying Xiao, David Nickle, Andrew Plump, Eric E. Schadt, Aldons J. Lusis, Pek Yee Lum
Journal: Journal of Clinical Investigation (2010)

Atherosclerosis represents the most significant risk factor for coronary artery disease (CAD), the leading cause of death in developed countries. To better understand the pathogenesis of atherosclerosis, we applied a likeli-hood-based model selection method to infer gene-disease causality relationships for the aortic lesion trait in a segregating mouse population demonstrating a spectrum of susceptibility to developing atherosclerotic lesions. We identified 292 genes that tested causal for aortic lesions from liver and adipose tissues of these mice, and we experimentally validated one of these candidate causal genes, complement component 3a receptor 1 (C3ar1), using a knockout mouse model. We also found that genes identified by this method overlapped with genes progressively regulated in the aortic arches of 2 mouse models of atherosclerosis during atherosclerotic lesion development. By comparing our gene set with findings from public human genome-wide association studies (GWAS) of CAD and related traits, we found that 5 genes identified by our study overlapped with published studies in humans in which they were identified as risk factors for multiple atherosclerosis-related pathologies, including myocardial infarction, serum uric acid levels, mean platelet volume, aortic root size, and heart failure. Candidate causal genes were also found to be enriched with CAD risk polymorphisms identified by the Wellcome Trust Case Control Consortium (WTCCC). Our findings therefore validate the ability of causality testing procedures to provide insights into the mechanisms underlying atherosclerosis development.