tbuckley/cabot-search huggingface dataset:
Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure.
Authors: A T Hirsch, C E Talsness, H Schunkert, M Paul, V J Dzau
Journal: Circulation Research (1991)

In addition to the circulating renin-angiotensin system, recent data demonstrate the existence of tissue renin-angiotensin systems that may be important in cardiovascular homeostasis. However, the relative activities of the circulating and tissue renin-angiotensin systems have not been examined previously in pathophysiological states, such as congestive heart failure. The present study was performed to examine the status of plasma and tissue angiotensin converting enzyme (ACE) activities in compensated experimental heart failure induced by coronary artery ligation in the rat. Three groups of male Sprague-Dawley rats were examined: 1) nonoperated rats (NO, n = 5), 2) sham-operated rats (SO, n = 5), and 3) heart failure rats (HF, n = 11). Rats were studied an averaged of 85 days postoperatively. In HF animals, plasma renin concentration and serum ACE activities were not different compared with NO and SO control animals. Cardiac ACE activity was 50% greater in the right ventricle than the interventricular septum in NO and SO rats. Both right ventricular and interventricular septal ACE activity increased approximately twofold in HF animals as compared with NO and SO groups (p less than 0.05). In contrast, pulmonary, aortic, and renal ACE activities were not altered in HF rats compared with control animals. A positive correlation existed between the histopathological size of myocardial infarction and the level of right ventricular ACE activity (r = 0.75, p less than or equal to 0.05). Such a relation between infarct size and either serum or noncardiac tissue ACE activities was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Gene Transfers from Nanoarchaeota to an Ancestor of Diplomonads and Parabasalids
Authors: J. O. Andersson
Journal: Molecular Biology and Evolution (2004)

Rare evolutionary events, such as lateral gene transfers and gene fusions, may be useful to pinpoint, and correlate the timing of, key branches across the tree of life. For example, the shared possession of a transferred gene indicates a phylogenetic relationship among organismal lineages by virtue of their shared common ancestral recipient. Here, we present phylogenetic analyses of prolyl-tRNA and alanyl-tRNA synthetase genes that indicate lateral gene transfer events to an ancestor of the diplomonads and parabasalids from lineages more closely related to the newly discovered archaeal hyperthermophile Nanoarchaeum equitans (Nanoarchaeota) than to Crenarchaeota or Euryarchaeota. The support for this scenario is strong from all applied phylogenetic methods for the alanyl-tRNA sequences, whereas the phylogenetic analyses of the prolyl-tRNA sequences show some disagreements between methods, indicating that the donor lineage cannot be identified with a high degree of certainty. However, in both trees, the diplomonads and parabasalids branch together within the Archaea, strongly suggesting that these two groups of unicellular eukaryotes, often regarded as the two earliest independent offshoots of the eukaryotic lineage, share a common ancestor to the exclusion of the eukaryotic root. Unfortunately, the phylogenetic analyses of these two aminoacyl-tRNA synthetase genes are inconclusive regarding the position of the diplomonad/parabasalid group within the eukaryotes. Our results also show that the lineage leading to Nanoarchaeota branched off from Euryarchaeota and Crenarchaeota before the divergence of diplomonads and parabasalids, that this unexplored archaeal diversity, currently only represented by the hyperthermophilic organism Nanoarchaeum equitans, may include members living in close proximity to mesophilic eukaryotes, and that the presence of split genes in the Nanoarchaeum genome is a derived feature.
Percutaneous coronary intervention for cardiogenic shock in the SHOCK trial
Authors: John G Webb, April M Lowe, Timothy A Sanborn, Harvey D White, Lynn A Sleeper, Ronald G Carere, Christopher E Buller, S.Chiu Wong, Jean Boland, Vlad Dzavik, Mark Porway, Gordon Pate, Geoffrey Bergman, Judith S Hochman
Journal: Journal of the American College of Cardiology (2003)
Recurrent diarrhoea and weight loss associated with cessation of smoking in a patient with undiagnosed coeliac disease
Authors: S J O VELDHUYZEN VAN ZANTEN
Journal: Gut (2001)

Case report —A 56 year old otherwise healthy male tried to quit his habit of smoking up to 16 cigarettes a day on four occasions. Each time approximately 3–6 weeks after he stopped smoking, watery non-bloody diarrhoea developed which also occurred at night. Frequency was 4–6 times per 24 hours. It was associated with a weight loss of at least 4.5 kg. There were no other symptoms. All of his symptoms subsided as soon as he resumed smoking. The diarrhoea also developed when he tried to quit smoking using either nicotine chewing gum or nicotine patches. The rest of …
Oral Rivaroxaban for Symptomatic Venous Thromboembolism
Authors: Rupert Bauersachs, Scott D Berkowitz, Benjamin Brenner, Harry R Buller, Hervé Decousus, Alex S Gallus, Anthonie W Lensing, Frank Misselwitz, Martin H Prins, Gary E Raskob, Annelise Segers, Peter Verhamme, Phil Wells, Giancarlo Agnelli, Henri Bounameaux, Alexander Cohen, Bruce L Davidson, Franco Piovella, Sebastian Schellong, Dominique Mottier
Journal: New England Journal of Medicine (2010)

Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.
Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis
Authors: E Gonzalez-Rey, P Anderson, M A Gonzalez, L Rico, D Buscher, M Delgado
Journal: Gut (2009)

<h3>Background and aims:</h3> Inflammatory bowel diseases (IBDs) are associated with uncontrolled innate and adaptive immunity against normal constituents, including commensal bacteria and microbial products. Mesenchymal stem cells (MSCs) suppress effector T cell responses and have beneficial effects in various immune disorders. This work investigates the therapeutic effects of human adipose-derived MSCs (hASCs) in various models of IBD and sepsis. <h3>Methods:</h3> Acute and chronic colitis was induced in mice with dextran sulfate sodium. Sepsis was induced by caecal ligation and puncture or by endotoxin injection. Colitic and septic mice were treated intraperitoneally with hASCs or murine ASCs, and diverse disease clinical signs and mortality were determined. The levels of various inflammatory cytokines and chemokines, T helper 1(Th1)-type response and generation of regulatory T cells (Treg) were determined in affected organs. <h3>Results:</h3> Systemic infusion of ASCs significantly ameliorated the clinical and histopathological severity of colitis, abrogating weight loss, diarrhoea and inflammation, and increasing survival. The therapeutic effect was associated with downregulation of the Th1-driven inflammatory responses. ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleuklin 10 (IL10), acting on macrophages. hASCs also impaired Th1 cell activation in both colonic mucosa and draining lymph nodes. The induction of IL10-secreting Treg was partially involved in the therapeutic effect of hASCs. Moreover, ASCs protected from severe sepsis by reducing the infiltration of inflammatory cells in various target organs and by downregulating the production of various inflammatory mediators. <h3>Conclusions:</h3> hASCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for IBD and sepsis.
Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive promoters to enhance beta-catenin/TCF-dependent transcription in colorectal cancer cells
Authors: Pinella Buongiorno, Vaijayanti V Pethe, George S Charames, Susmita Esufali, Bharati Bapat
Journal: Molecular Cancer (2008)

Abstract Background β-catenin is a key mediator of the canonical Wnt pathway as it associates with members of the T-cell factor (TCF) family at Wnt-responsive promoters to drive the transcription of Wnt target genes. Recently, we showed that Rac1 GTPase synergizes with β-catenin to increase the activity of a TCF-responsive reporter. This synergy was dependent on the nuclear presence of Rac1, since inhibition of its nuclear localization effectively abolished the stimulatory effect of Rac1 on TCF-responsive reporter activity. We hypothesised that Rac1 plays a direct role in enhancing the transcription of endogenous Wnt target genes by modulating the β-catenin/TCF transcription factor complex. Results We employed chromatin immunoprecipitation studies to demonstrate that Rac1 associates with the β-catenin/TCF complex at Wnt-responsive promoters of target genes. This association served to facilitate transcription, since overexpression of active Rac1 augmented Wnt target gene activation, whereas depletion of endogenous Rac1 by RNA interference abrogated this effect. In addition, the Rac1-specific exchange factor, Tiam1, potentiated the stimulatory effects of Rac1 on the canonical Wnt pathway. Tiam1 promoted the formation of a complex containing Rac1 and β-catenin. Furthermore, endogenous Tiam1 associated with endogenous β-catenin, and this interaction was enhanced in response to Wnt3a stimulation. Intriguingly, Tiam1 was recruited to Wnt-responsive promoters upon Wnt3a stimulation, whereas Rac1 was tethered to TCF binding elements in a Wnt-independent manner. Conclusion Taken together, our results suggest that Rac1 and the Rac1-specific activator Tiam1 are components of transcriptionally active β-catenin/TCF complexes at Wnt-responsive promoters, and the presence of Rac1 and Tiam1 within these complexes serves to enhance target gene transcription. Our results demonstrate a novel functional mechanism underlying the cross-talk between Rac1 and the canonical Wnt signalling pathway.
Delayed improvement of insulin secretion after autologous islet transplantation in partially pancreatectomized patients
Authors: Hye Seung Jung, Seong-Ho Choi, Sung-Joo Kim, Dong-Wook Choi, Jin-Seok Heo, Kyu Taek Lee, Jong Kyun Lee, Kee-Taek Jang, Byung-Wan Lee, Jae-Hwan Jee, Jung-Hyun Noh, In Kyung Jeong, Tae-Young Yang, Seung-Hoon Oh, You-Ran Ahn, Young-Seok Kim, Heesung No, Moon-Kyu Lee, Kwang-Won Kim
Journal: Metabolism (2009)
Phase I Trial of Intratumoral Injection of an Adenovirus Encoding Interleukin-12 for Advanced Digestive Tumors
Authors: Bruno Sangro, Guillermo Mazzolini, Juan Ruiz, Maite Herraiz, Jorge Quiroga, Ignacio Herrero, Alberto Benito, Javier Larrache, Jesus Pueyo, Jose Carlos Subtil, Cristina Olagüe, Josu Sola, Belén Sádaba, Carlos Lacasa, Ignacio Melero, Cheng Qian, Jesus Prieto
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate the feasibility and safety of intratumoral injection of an adenoviral vector encoding human interleukin-12 genes (Ad.IL-12) and secondarily, its biologic effect for the treatment of advanced digestive tumors. Patients and Methods Ad.IL-12 was administered in doses ranging from 2.5 × 10 10 to 3 × 10 12 viral particles, to seven cohorts of patients with advanced pancreatic, colorectal, or primary liver malignancies. Patients were thoroughly assessed for toxicity, and antitumor response was evaluated by imaging techniques, tumor biopsy, and hypersensitivity skin tests. Patients with stable disease and no serious adverse reactions were allowed to receive up to 3 monthly doses of Ad.IL-12. Results Twenty-one patients (nine with primary liver, five with colorectal, and seven with pancreatic cancers) received a total of 44 injections. Ad.IL-12 was well tolerated, and dose-limiting toxicity was not reached. Frequent but transient adverse reactions, including fever, malaise, sweating, and lymphopenia, seemed to be related to vector injection rather than to transgene expression. No cumulative toxicity was observed. In four of 10 assessable patients, a significant increase in tumor infiltration by effector immune cells was apparent. A partial objective remission of the injected tumor mass was observed in a patient with hepatocellular carcinoma. Stable disease was observed in 29% of patients, mainly those with primary liver cancer. Conclusion Intratumoral injection of up to 3 × 10 12 viral particles of Ad.IL-12 to patients with advanced digestive malignancies is a feasible and well-tolerated procedure that exerts only mild antitumor effects.
Restless Legs Syndrome and Quality of Sleep in Type 2 Diabetes
Authors: Lívia A. Lopes, Camila de M.M. Lins, Vanessa G. Adeodato, Diana P. Quental, Pedro F.C. de Bruin, Renan M. Montenegro, Veralice M.S. de Bruin
Journal: Diabetes Care (2005)

To investigate the presence of restless legs syndrome (RLS) and the quality of sleep in a population of type 2 diabetic patients.The study population was composed of 100 consecutive patients regularly attending a diabetes clinic at the University Hospital of the Federal University of Ceará. The subjects' quality of sleep was assessed by the Pittsburgh Sleep Quality Index, and excessive daytime sleepiness (EDS) was measured by the Epworth Sleepiness Scale. The RLS was diagnosed using the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Other relevant clinical and laboratory parameters were obtained by interview and chart review.RLS was found in 27% of patients. Poor sleep quality was present in 45% of cases and was associated with age (P = 0.04), peripheral neuropathy (P = 0.001), and RLS (P = 0.000). EDS was found in 26% of patients. Logistic regression analysis revealed an association between RLS and peripheral neuropathy (odds ratio 12.85 [95% CI 2.83-58.40], P = 0.001).RLS is common in type 2 diabetic patients and can be a major cause of sleep disruption in these patients.
Mixed Messages
Authors: Kenneth B. Margulies, Sunil Matiwala, Carla Cornejo, Henrik Olsen, William A. Craven, Daniel Bednarik
Journal: Circulation Research (2005)

In previous studies, mechanical support of medically refractory hearts with a left ventricular assist device (LVAD) has induced regression of many morphological and functional abnormalities characteristic of failing human hearts. To identify transcriptional adaptations in failing and LVAD-supported hearts, we performed a comprehensive transcription analysis using the Affymetrix microarray platform and 199 human myocardial samples from nonfailing, failing, and LVAD-supported human hearts. We also used a novel analytical strategy that defines patterns of interest based on multiple intergroup comparisons. Although over 3088 transcripts exhibited significantly altered abundance in heart failure, most of these did not exhibit a consistent response to LVAD support based on our analysis. Of those 238 with a consistent response to LVAD support, more than 75% exhibited persistence or exacerbation of HF-associated transcriptional abnormalities whereas only 11%, 5%, and 2% exhibited partial recovery, normalization, and overcorrection responses, respectively. Even among genes implicated by previous reports of LVAD-associated myocardial improvements, partial or complete normalization of transcription did not predominate. The magnitude of differences in transcript abundance between nonfailing and failing hearts, and between failing an LVAD-supported hearts, tended to be low with changes greater than or equal to 2-fold infrequently observed. Our results indicate that morphological or functional myocardial improvements may occur without widespread normalization of pathological transcriptional patterns. These observations also suggest that many failure-associated transcriptional changes have only a limited role in regulating cardiac structure and function and may represent epiphenomena and/or nonspecific myocardial plasticity responses. Differences in mRNA localization, translation efficiency, and posttranslational protein modifications or interactions may be more pivotal in regulating myocardial structure and function.
Calcineurin Plays a Critical Role in Pressure Overload–Induced Cardiac Hypertrophy
Authors: Masaki Shimoyama, Doubun Hayashi, Eiki Takimoto, Yunzeng Zou, Toru Oka, Hiroki Uozumi, Sumiyo Kudoh, Futoshi Shibasaki, Yoshio Yazaki, Ryozo Nagai, Issei Komuro
Journal: Circulation (1999)

Cardiac hypertrophy is a fundamental adaptive response to hemodynamic overload; how mechanical load induces cardiac hypertrophy, however, remains elusive. It was recently reported that activation of a calcium-dependent phosphatase, calcineurin, induces cardiac hypertrophy. In the present study, we examined whether calcineurin plays a critical role in pressure overload-induced cardiac hypertrophy.Pressure overload produced by constriction of the abdominal aorta increased the activity of calcineurin in the rat heart and induced cardiac hypertrophy, including reprogramming of gene expression. Treatment of rats with a calcineurin inhibitor, FK506, inhibited the activation of calcineurin and prevented the pressure overload-induced cardiac hypertrophy and fibrosis without change of hemodynamic parameters. Load-induced expression of immediate-early-response genes and fetal genes was also suppressed by the FK506 treatment.The present results suggest that the calcineurin signaling pathway plays a pivotal role in load-induced cardiac hypertrophy and may pave the way for a novel pharmacological approach to prevent cardiac hypertrophy.
Adverse pulmonary vascular effects of high dose tricyclic antidepressants: acute and chronic animal studies
Authors: X. Liu, C.J. Emery, E. Laude, J. Herget, G. Gill, G. Cope, G.R. Barer
Journal: European Respiratory Journal (2002)

Overdose of tricyclic antidepressants, which inhibit cellular serotonin (5-HT) uptake, sometimes causes acute respiratory syndrome-like symptoms. Their acute and chronic cardiopulmonary actions, which might be implicated, utilising both in vivo and ex vivo animal studies, were investigated in this study. Acute amitriptyline (AMI), iprindole and imipramine caused dose-dependent prolonged rises in pulmonary artery pressure and oedema in anaesthetised cats in vivo . Acute AMI, in isolated ex vivo blood-perfused rat lungs, also caused dose-dependent sustained vasoconstriction, which could be attenuated with either calcium channel inhibition or a nitric oxide donor. It was demonstrated that the pressor effects of AMI were not due to release of histamine, serotonin, noradrenaline, or the activities of cycloxygenase or lipoxygenase. After AMI, hypoxic pulmonary vasoconstriction and the pressor actions of 5‐HT and noradrenaline were diminished, possibly due to uptake inhibition. Activities of the endothelial-based enzymes, nitric oxide synthase and endothelin-converting enzyme, were undiminished. Large acute doses of AMI caused oedema with rupture of capillaries and alveolar epithelium. Chronic iprindole raised pulmonary artery pressure and right ventricle (RV)/left ventricle (LV) + septal (S) weight. Chronic AMI led to attenuation of the pressor action of 5‐HT, especially when associated with chronic hypoxic-induced pulmonary hypertension. RV/LV+S weight increased, attributable to LV decline. The acute and chronic effects observed might have relevance to clinical overdose, while the attenuation of acute effects offers possible therapeutic options.
Guidelines for the management of work-related asthma
Authors: X. Baur, T. Sigsgaard, T.B. Aasen, P.S. Burge, D. Heederik, P. Henneberger, P. Maestrelli, J. Rooyackers, V. Schlünssen, O. Vandenplas, D. Wilken
Journal: European Respiratory Journal (2012)

Work-related asthma, which includes occupational asthma and work-aggravated asthma, has become one of the most prevalent occupational lung diseases. These guidelines aim to upgrade occupational health standards, contribute importantly to transnational legal harmonisation and reduce the high socio-economic burden caused by this disorder. A systematic literature search related to five key questions was performed: diagnostics; risk factors; outcome of management options; medical screening and surveillance; controlling exposure for primary prevention. Each of the 1,329 retrieved papers was reviewed by two experts, followed by Scottish Intercollegiate Guidelines Network grading, and formulation of statements graded according to the Royal College of General Practitioners’ three-star system. Recommendations were made on the basis of the evidence-based statements, which comprise the following major evidence-based strategic points. 1) A comprehensive diagnostic approach considering the individual specific aspects is recommended. 2) Early recognition and diagnosis is necessary for timely and appropriate preventative measures. 3) A stratified medical screening strategy and surveillance programme should be applied to at-risk workers. 4) Whenever possible, removing exposure to the causative agent should be achieved, as it leads to the best health outcome. If this is not possible, reduction is the second best option, whereas respirators are of limited value. 5) Exposure elimination should be the preferred primary prevention approach.
Open Access gains attention in scholar communication.
Authors: Paul J Chiao, Christian Schmidt
Journal: Molecular Cancer (2004)

Open Access is one of the attempts to maximize the exchange of information, and therefore benefits the scholar communication [1].Molecular Cancer offers Open Access to all of its content, thereby providing a platform to present information to specialists and the public in order to further promote free exchange of ideas, concepts and findings in all fields of cancer-related biomedical science.
Determining the running-related injury risk factors in long distance runners
Authors: J Genin, R Mann, D Theisen
Journal: British Journal of Sports Medicine (2011)

Background Increased popularity in long-distance running over the last 30–40 years has induced an increase in the incidence of running-related injuries (RRI). Among others, running experience could be a determining factor in the RRI incidence. Objective To explore whether novice runners sustain more RRI than experienced runners and to determine RRI risk factor variables. Design Prospective epidemiological study. Setting A 27-week follow-up of runners at the Luxembourg National Sport Centre ending on the ING-Europe (semi)Marathon of Luxembourg (05.15.2010). Participants 39 compliant runners (40.2±8.5 years) out of the initial cohort (n=85). Assessment of risk factors Extrinsic, training-related characteristics (context, volume, etc). Main outcome measurements Running and other sports data were recorded using an innovative internet-based diary. Similarly, RRIs, which were defined as any pain or physical complaint impeding or altering a training session for at least 1 day, were recorded. Results From the 39 athletes, 14 were classified as novice runners (ie, &lt;3 months of regular running during the 12 months before the training period). Overall RRI incidence was evaluated at 8.07 RRI/1000 h of running. The RRI incidence was 3.3 times higher (95%CI 1.27 to 8.54) in novice than in experienced runners (16.8 and 5.1 RRI/1000 h of running, respectively; p=0.009), confirming the initial hypothesis. Dichotomous RRI risk factors such as gender or running experience were not significant. RRI incidence was significantly associated with a lower competition volume per week, a lower number of training session, a lower percentage of competition run on a soft surface and a higher average work rate (av. HR/(220-age) during competition. A logistic regression including all individual variables with a p-value&lt;0.2 yielded no significant results. Conclusion Although the initial hypothesis was confirmed, no risk factors were significant within the logistic regression. In order to be able to construct an individual RRI risk profile, a greater sample size is necessary to provide more conclusive results.