tbuckley/cabot-search huggingface dataset:
Endogenous Ouabain
Authors: Julie R. Murrell, Jeffrey D. Randall, James Rosoff, Ji-liang Zhao, Roderick V. Jensen, Steven R. Gullans, Garner T. Haupert
Journal: Circulation (2005)

Mammalian tissues contain a presumed endogenous Na+, K(+)-ATPase inhibitor that binds reversibly to the Na+ pump with high affinity and specificity. The inhibitor has been linked to the pathogenesis of experimental volume-expanded and human essential hypertension. This compound has been isolated from mammalian hypothalamus and appears to be an isomer of the plant-derived cardiac glycoside ouabain, if not ouabain itself. The objective of this study was to test the hypothesis that a biosynthetic pathway exists in mammalian tissues to produce a steroid derivative closely related to plant cardiac glycosides.Using bioinformatics and genomic techniques, Milan hypertensive rat tissues were studied because this strain has a 10-fold increase in hypothalamic ouabain-like compound that is linked to the pathogenesis of the hypertension. A putative steroid biosynthetic pathway was constructed and candidate genes encoding enzymes in this pathway were identified from sequence databases. Differential expression of selected genes in the pathway was studied by microarray analysis and quantitative polymerase chain reaction, with functional validation by gene silencing using small interfering RNAs. Marked upregulation of genes coding for P450 side chain cleavage and Delta5-3beta-hydroxysteroid dehydrogenase/Delta5-Delta4- isomerase enzymes in hypertensive hypothalamus but not adrenal was found, compared with normotensive Milan rats. Knockdown of the latter gene decreased production of ouabain-like factor from neural tissue.Our findings support the possibility that a unique steroid biosynthetic circuit exists in Milan rat brain, functioning independently from adrenal, which could account for the overproduction of the hypothalamic ouabain-like compound in this species.
Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats
Authors: A. Tarasiuk, N. Berdugo-Boura, A. Troib, Y. Segev
Journal: European Respiratory Journal (2011)

Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT 2 receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (p&lt;0.01). In UAO rats, the duration of wakefulness was elevated and the duration of SWS, paradoxical sleep and slow-wave activity was reduced (p&lt;0.001). Ritanserin alleviated these effects, i.e. normalised hypothalamic GHRH content, decreased wake duration, increased duration and depth of SWS, and attenuated growth impairment (p&lt;0.001). Here, we present evidence that growth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.
Mental Health Problems Among Adults in Tsunami-Affected Areas in Southern Thailand
Authors: Frits van Griensven
Journal: JAMA (2006)

ContextOn December 26, 2004, an undersea earthquake occurred off the northwestern coast of Sumatra, Indonesia. The tsunami that followed severely affected all 6 southwestern provinces of Thailand, where 5395 individuals died, 2991 were unaccounted for, and 8457 were injured.ObjectiveTo assess the prevalence of symptoms of posttraumatic stress disorder (PTSD), anxiety, and depression among individuals residing in areas affected by the tsunami in southern Thailand as part of a public health emergency response and rapid assessment.Design, Setting, and ParticipantsA multistage, cluster, population-based mental health survey was conducted from February 15 to 22, 2005, of random samples of displaced (n = 371) and nondisplaced persons in Phang Nga province (n = 322) and nondisplaced persons in the provinces of Krabi and Phuket (n = 368). Data were collected using an interviewer-administered questionnaire on handheld computers. A surveillance follow-up survey of the displaced persons (n = 371) and nondisplaced persons (n = 322) in Phang Na was conducted in September 2005.Main Outcomes MeasuresMedical Outcomes Study-36 Short-Form Health Survey SF-36 to assess self-perceived general health, bodily pain, and social and emotional functioning; the Harvard Trauma Questionnaire to assess tsunami-specific traumatic events; and the Hopkins Checklist-25 to detect symptoms of anxiety and depression.ResultsParticipation rates for displaced and nondisplaced persons in the rapid assessment survey were 69% and 58%, respectively. Symptoms of PTSD were reported by 12% of displaced and 7% of nondisplaced persons in Phang Nga and 3% of nondisplaced persons in Krabi and Phuket. Anxiety symptoms were reported by 37% of displaced and 30% of nondisplaced persons in Phang Nga and 22% of nondisplaced persons in Krabi and Phuket. Symptoms of depression were reported by 30% of displaced and 21% of nondisplaced persons in Phang Nga and 10% of nondisplaced persons in Krabi and Phuket. In multivariate analysis, loss of livelihood was independently and significantly associated with symptoms of all 3 mental health outcomes (PTSD, anxiety, and depression). In the 9-month follow-up surveillance survey of 270 (73%) displaced and 250 (80%) nondisplaced participants in Phang Nga, prevalence rates of symptoms of PTSD, anxiety, and depression among displaced persons decreased to 7%, 24.8%, and 16.7%, respectively, and among nondisplaced persons, prevalence rates decreased to 2.3%, 25.9%, and 14.3%, respectively.ConclusionsAmong survivors of the tsunami in southern Thailand, elevated rates of symptoms of PTSD, anxiety, and depression were reported 8 weeks after the disaster, with higher rates for anxiety and depression than PTSD symptoms. Nine months after the disaster, the rates of those reporting these symptoms decreased but were still elevated. This information is important for directing, strengthening, and evaluating posttsunami mental health needs and interventions.
The effect of volume targeted pressure support (PS) ventilation with autotitrating expiratory positive airways pressure (EPAP) and back up rate (BUR) on sleep quality in COPD-obstructive sleep apnoea (OSA) overlap syndrome
Authors: Patrick Murphy, Gill Arbane, Deepak Jayaram, Susannah Leaver, Michael Polkey, Nicholas Hart
Journal: European Respiratory Journal (2013)

Introduction  The mixed ventilatory defect in patients with respiratory failure secondary to COPD-OSA overlap syndrome makes the set up of nocturnal ventilation challenging. Although ‘automated’ modes of non-invasive ventilation (NIV) may have a role in this subgroup, there are concerns about their impact on sleep disruption.  Method  10 patients on home NIV were recruited. A non-randomised design was used. Each patient underwent 14 day actigraphy prior to polysomnography (PSG) using their usual NIV then repeat PSG with AE AVAPS (Philips-Respironics, Murrysville, US) mode; setup protocol (PS 4-26 cmH2O, EPAP 4-14 cmH2O, Vte 10ml/kg; ideal body weight). Then a further 14 day actigraphy prior to repeat assessment.  Results  Data are presented for the 7 patients who have completed the trial protocol; age 64±5 years, FEV1 33±14% and PaCO2 7.2±2.4kPa. Mean fixed level NIV settings (cmH2O): EPAP 7±4, PS 20±5 and BUR 11±3bpm. AVAPS AE mode mean set Vte 647±93ml. Objective and subjective sleep data is provided:  A significant improvement in NIV use occurred over the initial trial period (Δ152min, 95%CI 26-277, p=0.027).  Conclusion  In this pre-post interventional trial, automated modes of NIV provide adequate control of nocturnal hypoventilation and upper airways obstruction as well as enhancing sleep efficiency and NIV adherence.
Rituximab for steroid-refractory chronic graft-versus-host disease
Authors: Corey Cutler, David Miklos, Haesook T. Kim, Nathaniel Treister, Sook-Bin Woo, Don Bienfang, Lloyd B. Klickstein, Jesse Levin, Katherine Miller, Carol Reynolds, Rebecca Macdonell, Mildred Pasek, Stephanie J. Lee, Vincent Ho, Robert Soiffer, Joseph H. Antin, Jerome Ritz, Edwin Alyea
Journal: Blood (2006)
<scp>MPLA</scp> shows attenuated pro‐inflammatory properties and diminished capacity to activate mast cells in comparison with <scp>LPS</scp>
Authors: S. Schülke, A. Flaczyk, L. Vogel, N. Gaudenzio, I. Angers, B. Löschner, S. Wolfheimer, I. Spreitzer, S. Qureshi, M. Tsai, S. Galli, S. Vieths, S. Scheurer
Journal: Allergy (2015)

Abstract Background Monophosphoryl lipid A ( MPLA ), a nontoxic TLR 4 ligand derived from lipopolysaccharide ( LPS ), is used clinically as an adjuvant in cancer, hepatitis, and malaria vaccines and in allergen‐specific immunotherapy. Nevertheless, its cell‐activating effects have not been analyzed in a comprehensive direct comparison including a wide range of different immune cells. Therefore, the objective of this study was the side‐by‐side comparison of the immune‐modulating properties of MPLA and LPS on different immune cells. Methods Immune‐activating properties of MPLA and LPS were compared in human monocytes and mast cells ( MC s), a mouse endotoxin shock model ( ESM ), and mouse bone marrow ( BM )‐derived myeloid dendritic cells ( mDC s), T cells ( TC s), B cells, and MC s. Results In a mouse in vivo ESM and a human ex vivo monocyte activation test ( MAT ), MPLA induced the same cytokine secretion pattern as LPS ( ESM : IL ‐6, IL ‐12, TNF ‐α; MAT : IL ‐1β, IL ‐6, TNF ‐α), albeit at lower levels. Mouse mDC s and ex vivo isolated B cells stimulated with MPLA required a higher threshold to induce TRIF‐dependent cytokine secretion ( IL ‐1β, IL ‐6, IL ‐10, and TNF ‐α) than did LPS ‐stimulated cells. In mDC : DO 11.10 CD 4 TC cocultures, stimulation with MPLA , but not with LPS , resulted in enhanced OVA ‐specific IL ‐4 and IL ‐5 secretion from DO 11.10 CD 4 TC s. Unexpectedly, in both human and mouse MC s, MPLA , unlike LPS , did not elicit secretion of pro‐inflammatory cytokines. Conclusions Compared to LPS , MPLA induced a qualitatively similar, but less potent pro‐inflammatory immune response, but was unable to activate human or mouse MC s.
Some Comments on the History and Experimental Explorations of Metal Carcinogens and Cancers&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: W C Hueper
Journal: JNCI Journal of the National Cancer Institute (1979)

The history of metal carcinogens began around 1935, when cancers of the lung were discovered in chromate workers and cancers of the lung and nasal sinuses were found in nickel refiners. Since then other metals and metal compounds have been added to the list of metal carcinogens (beryllium, cadmium, cobalt, lead, selenium, mercury, gold, and zinc), all of which are important to industry and medicine, but most of which are potentially harmful to humans. The carcinogenic role of iron has remained controversial. The marked diversity of physiologic and toxicologic reactions elicited by metals has thus far prevented development of a unifying hypothesis of the causal carcinogenic mechanism. The increased importance of certain metals (chromates, nickel) as environmental carcinogen. In recent decades approaches that of certain minerals (asbestos, arsenicals) because of their extensive use in modern Industry and consumer goods; thus occupational and environmental cancer hazards to man are increased. The first cancer in chromate workers was litigated around 1944 and was followed in rapid succession by litigations from this and other chromate plants in the United States. Existing epidemiologic data on this subject, however, are defective and tend to give too low incidence rates. Moreover, several large occupational groups completely lack data on the presence and severity of cancer risks caused by chromium alloys and chromic acid. Experiments on several animal species given hexavalent and trivalent chromium compounds have firmly established the carcinogenicity of chromium when it is introduced in a biologically available form permitting interreaction between the carcinogen and tissue. Both sarcomas and carcinomas can thus be induced. Although cancers in nickel workers have not yet been recorded from plants In the United States, they are on record in England, Canade, Norway, the German Democratic Republic, Japan, and the U.S.S.R., where either the nickel carbonyl Mond process or electrolytic extraction is used. This observation as well as the ease with which experimental animals develop cancers after introduction of nickel compounds and metallic nickel indicates that nickel is the carcinogenic agent. Intrapleural and intrapulmonary administration of powdered iron prepared by the degradation of iron carbonyl did not result in cancers in rats but caused large granulomas. The injection of uranium, a low-level radioactive element, into the marrow cavity of the rat femur induced osteogenic sarcomas. Whether such cancers are induced by radiation or metal or both is uncertaln.
Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: meta-analysis of cohort studies
Authors: J. Verhaegen, I. D. Gallos, N. M. van Mello, M. Abdel-Aziz, Y. Takwoingi, H. Harb, J. J. Deeks, B. W. J. Mol, A. Coomarasamy
Journal: BMJ (2012)

<b>Objective</b> To determine the accuracy with which a single progesterone measurement in early pregnancy discriminates between viable and non-viable pregnancy. <b>Design</b> Systematic review and meta-analysis of diagnostic accuracy studies. <b>Data sources</b> Medline, Embase, CINAHL, Web of Science, ProQuest, Conference Proceedings Citation Index, and the Cochrane Library from inception until April 2012, plus reference lists of relevant studies. <b>Study selection</b> Studies were selected on the basis of participants (women with spontaneous pregnancy of less than 14 weeks of gestation); test (single serum progesterone measurement); outcome (viable intrauterine pregnancy, miscarriage, or ectopic pregnancy) diagnosed on the basis of combinations of pregnancy test, ultrasound scan, laparoscopy, and histological examination; design (cohort studies of test accuracy); and sufficient data being reported. <b>Results</b> 26 cohort studies, including 9436 pregnant women, were included, consisting of 7 studies in women with symptoms and inconclusive ultrasound assessment and 19 studies in women with symptoms alone. Among women with symptoms and inconclusive ultrasound assessments, the progesterone test (5 studies with 1998 participants and cut-off values from 3.2 to 6 ng/mL) predicted a non-viable pregnancy with pooled sensitivity of 74.6% (95% confidence interval 50.6% to 89.4%), specificity of 98.4% (90.9% to 99.7%), positive likelihood ratio of 45 (7.1 to 289), and negative likelihood ratio of 0.26 (0.12 to 0.57). The median prevalence of a non-viable pregnancy was 73.2%, and the probability of a non-viable pregnancy was raised to 99.2% if the progesterone was low. For women with symptoms alone, the progesterone test had a higher specificity when a threshold of 10 ng/mL was used (9 studies with 4689 participants) and predicted a non-viable pregnancy with pooled sensitivity of 66.5% (53.6% to 77.4%), specificity of 96.3% (91.1% to 98.5%), positive likelihood ratio of 18 (7.2 to 45), and negative likelihood ratio of 0.35 (0.24 to 0.50). The probability of a non-viable pregnancy was raised from 62.9% to 96.8%. <b>Conclusion</b> A single progesterone measurement for women in early pregnancy presenting with bleeding or pain and inconclusive ultrasound assessments can rule out a viable pregnancy.
Modifications of Chromatin Dynamics Control Smad2 Pathway Activation in Aneurysmal Smooth Muscle Cells
Authors: Delphine Gomez, Ketty Kessler, Jean-Baptiste Michel, Roger Vranckx
Journal: Circulation Research (2013)

The activation of the Smad2 signaling pathway is thought to play an important role in human aneurysmal diseases as described by an important body of research. We previously showed that constitutive Smad2 activation is associated with Smad2 mRNA overexpression in aneurysmal vascular smooth muscle cells (VSMCs), which is dependent on epigenetic regulation of the SMAD2 promoter involving histone modifications. However, the underlying molecular mechanisms controlling Smad2 overexpression are currently unknown.The aim of the present study is to understand the mechanisms regulating the constitutive Smad2 overexpression in VSMCs by identification of the histone-modifying enzymes, transcription factors, and cofactors responsible for Smad2 promoter activation in aneurysmal disease.This study was performed on medial tissue extracts and primary cultures of VSMCs of human thoracic aneurysms (n=17) and normal thoracic aortas (n=10). Here, we demonstrate that the activation of SMAD2 promoter is driven by the recruitment of a multipartner complex, including the transcription factor p53 and histone acetyltransferases. Remarkably, the transcriptional regulatory network of the SMAD2 promoter is dramatically altered in human aneurysmal VSMCs in vitro and in situ with a switch from Myc-dependent repression of SMAD2 in normal vessel to a p53-dependent activation of SMAD2 in aneurysms. Furthermore, histone acetyltransferases p300 and P300/CBP-associated protein play a major role in SMAD2 promoter activation by acting on histone acetylation, p53 recruitment, and acetylation.These results provide evidence for a major role of p53 and the complex composed of p300 and p300/CBP-associated protein in Smad2 activation in human aneurysmal VSMCs.
Use of continuous positive airway pressure during flexible bronchoscopy in young children
Authors: D. Trachsel, T. O. Erb, F. J. Frei, J. Hammer
Journal: European Respiratory Journal (2005)

Young children are at increased risk for hypoxaemia and hypercapnia during flexible bronchoscopy due to the small size and increased collapsibility of their airways. Various strategies are used to prevent hypoventilation and to provide oxygen during the procedure. The aim of this study was to assess the impact of continuous positive airway pressure (CPAP) on ventilation during flexible bronchoscopy in infants and young children. Tidal breathing was measured in 16 spontaneously breathing and deeply sedated children, aged 3–25 months, by ultrasound spirometry via an airway endoscopy mask. Measurements were made with the tip of the bronchoscope positioned in the pharynx with no CPAP, and in mid-trachea with 0, 5 and 10 cmH 2 O of CPAP. Transition of the bronchoscope through the vocal cords was associated with significant decreases of tidal volumes (5.0±0.5 versus 3.4±0.5 mL·kg −1 ), peak tidal expiratory flows (78±12 versus 52±10 mL·s −1 ) and peak tidal inspiratory flows (98±15 versus 66±12 mL·kg −1 ). CPAP (5–10 cmH 2 O) induced almost complete reversal of these changes. In conclusion, it is shown here that flexible bronchoscopy in spontaneously breathing young children is associated with significant decreases in tidal volume and respiratory flow. These changes are largely reversible with continuous positive airway pressure.
High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi
Authors: Kathryn E Holt, Julian Parkhill, Camila J Mazzoni, Philippe Roumagnac, François-Xavier Weill, Ian Goodhead, Richard Rance, Stephen Baker, Duncan J Maskell, John Wain, Christiane Dolecek, Mark Achtman, Gordon Dougan
Journal: Nature Genetics (2008)
Transient Global Amnesia
Authors: R. M. Kennedy
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Because of recent experience with a patient with transient global amnesia (TGA), we, too, have been reviewing our medical records of patients with this disorder, as did Nausieda and Sherman (241:392, 1979). One of our patients is a previously healthy 52-year-old right-handed man who has had one episode of a stereotypical attack of TGA.<sup>1</sup>Findings from his neurological examination were normal shortly after the episode. Results of laboratory tests, including computerized tomographic head scan, were normal except for two EEGs, which were severely abnormal, showing active single left temporal spike discharge with paroxysmal generalized delta slowing. In reviewing the records of seven other patients with TGA, we found two others with similar EEG findings—one in whom major motor seizures developed. These findings focused us toward the concept that TGA may be on occasion an epileptogenic phenomena rather than a vascular one, per se. For our patient,
Long-Term Survival and Dialysis Dependency Following Acute Kidney Injury in Intensive Care: Extended Follow-up of a Randomized Controlled Trial
Authors: Martin Gallagher, Alan Cass, Rinaldo Bellomo, Simon Finfer, David Gattas, Joanne Lee, Serigne Lo, Shay McGuinness, John Myburgh, Rachael Parke, Dorrilyn Rajbhandari
Journal: PLoS Medicine (2014)

Martin Gallagher and colleagues examine the long-term outcomes of renal replacement therapy (RRT) dosing in patients with acute kidney injury randomized to normal vs. augmented RRT. Please see later in the article for the Editors' Summary
Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer -A study of the OVCAD consortium
Authors: Stefanie Aust, Anna Bachmayr-Heyda, Petra Pateisky, Dan Tong, Silvia Darb-Esfahani, Carsten Denkert, Radoslav Chekerov, Jalid Sehouli, Sven Mahner, Toon Van Gorp, Ignace Vergote, Paul Speiser, Reinhard Horvat, Robert Zeillinger, Dietmar Pils
Journal: Molecular Cancer (2012)

Abstract Background The role of the tumor necrosis factor receptor associated protein 1 (TRAP1) – supposed to be involved in protection of cells from apoptosis and oxidative stress – has just started to be investigated in ovarian cancer. TRAP1 has been shown to be estrogen up-regulated in estrogen receptor α (ERα) positive ovarian cancer cells. The clinical impact of TRAP1 is not clear so far and the significance of ERα expression as therapeutic and prognostic marker is still controversial. Therefore, we investigated the importance of TRAP1 together with ERα in regard to clinicopathological parameters, chemotherapy response, and survival. Methods and results Expressions of TRAP1 and ERα were evaluated by immunohistochemical staining of tissue microarrays comprised of 208 ovarian cancer samples. TRAP1 was highly expressed in 55% and ERα was expressed in 52% of all cases. High TRAP1 expression correlated significantly with ERα (p &lt; 0.001) but high TRAP1 expression was also found in 42% of ERα negative cases. High TRAP1 expression correlated significantly with favorable chemotherapy-response (HR = 0.48; 95%CI 0.24-0.96, p=0.037) and showed a significant impact on overall survival (OS) (HR = 0.65; 95%CI 0.43-0.99, p = 0.044). ERα expression was a favorable prognostic factor for OS in univariate and multivariate analyses. Interestingly, the combined pattern (ERα positive and/or TRAP1-high) revealed the strongest independent and significant positive influence on OS (HR = 0.41; 95%CI 0.27-0.64). Conclusion Immunohistochemical evaluation of TRAP1 together with ERα provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival, rendering TRAP1 as interesting scientific and therapeutic target.