tbuckley/cabot-search huggingface dataset:
Activation of retinoic X receptor and peroxisome proliferator–activated receptor-γ inhibits nitric oxide and tumor necrosis factor-α production in rat Kupffer cells
Authors: Koutaro Uchimura, Makoto Nakamuta, Munechika Enjoji, Takashi Irie, Rie Sugimoto, Tatsushi Muta, Hiroaki Iwamoto, Hajime Nawata
Journal: Hepatology (2001)

Activators of peroxisome proliferator–activated receptor γ (PPARγ), which forms a heterodimer with retinoic X receptor (RXR), inhibit the production of certain inflammatory mediators. To clarify the role of the PPARγ:RXR signaling pathway in Kupffer cells, we studied the effect of an RXR agonist and PPARγ agonist on LPS–induced nitric oxide (NO) and tumor necrosis factor–α (TNF–α) production. An RXR–specific agonist, Ro47–5944, and a PPARγ–specific agonist, AD4833 (pioglitazone hydrochloride), each inhibited LPS–induced NO and TNF–α production. The combined treatment of Ro47–5944 and AD4833 resulted in enhanced inhibition, and suppressed the mRNA levels of NO and TNF–α. PPARγ:RXR activation did not affect the level of LPS–induced phosphorylation of c–jun N–terminal kinase and p38 mitogen–activated protein kinase. PPARγ:RXR activation also did not affect nuclear factor kappa B (NF–κB) nuclear translocation nor NF–κB and activator protein 1 (AP–1) activation in the electrophoretic mobility–shift assay. Finally, PPARγ:RXR activation suppressed the LPS–induced promoter activity of the NF–κB–luciferase reporter gene in RAW 264.7 cells. These data imply that PPARγ:RXR activation suppresses LPS–induced NO and TNF–α production in Kupffer cells, and that this inhibition occurred at the transcriptional level. Although no consensus PPARγ:RXR–responsive element in the promoter regions of the inducible isoform of nitric oxide synthase (iNOS) and TNF–α genes was found, PPARγ:RXR may interfere with NF–κB and AP–1 transcriptional activity. Our data also suggest a potential therapeutic approach for moderating hepatic injury such as endotoxin shock in which Kupffer cell activation has been implicated.
Conserved Gene Order at the Nuclear Periphery in Drosophila
Authors: José M. Ranz, Carlos Díaz-Castillo, Rita Petersen
Journal: Molecular Biology and Evolution (2011)

Whether higher-order chromatin organization is related to genome stability over evolutionary time remains elusive. We find that regions of conserved gene order across the genus Drosophila are larger if they harbor genes bound by B-type lamin (Lam) and Suppressor of Under-Replication (SUUR), two proteins located at the nuclear periphery. Low recombination rates and coexpression of genes in regions of conserved gene order do not explain the lower probability of disruption in these regions by genome rearrangements. Instead, we find a significant colocalization between evolutionarily stable genomic regions associated with Lam and sequences thought to regulate local gene expression, which have the potential to impose constraints on genome rearrangement. At least in the genus Drosophila, localization of particular genomic regions at the nuclear periphery is intimately associated with their long-term integrity during evolution.
A Follow-up Study of Residents in Internal-Medicine, Pediatrics and Obstetrics-Gynecology Training Programs in Massachusetts
Authors: Henry Wechsler, Joseph L. Dorsey, Joanne D. Bovey
Journal: New England Journal of Medicine (1978)

Special Article from The New England Journal of Medicine — A Follow-up Study of Residents in Internal-Medicine, Pediatrics and Obstetrics-Gynecology Training Programs in Massachusetts — Implications for the Supply of Primary-Care Physicians
Iraqi missile attacks on Israel. The association of mortality with a life-threatening stressor
Authors: J. D. Kark
Journal: JAMA (1995)

The imminent deadline for the 1991 Persian Gulf War and, subsequently, the 18 missile attacks by Iraq on Israel represented an unusual, short-term, life-threatening stressor for an entire nation. We studied mortality in Israel in January and February 1991 to determine whether excess deaths were precipitated on days of missile attacks.A time-series mortality study.The state of Israel.All Israelis aged 25 years and older.Daily mortality by sex, age, region, underlying cause, and place of death.On January 18, 1991, the day of the first strike on Israeli cities, a 58% increment in total mortality occurred in the Israeli population (95% confidence interval [CI], 34% to 86%; P < .0001), a 77% excess (95% CI, 40% to 120%) in women and a 41% excess (95% CI, 10% to 79%) in men. This excess mortality occurred largely in the targeted Tel Aviv-central coastal plain and Haifa regions from cardiovascular causes and mainly out of hospital, significantly more so (P < .01) in women than men. Subsequently, on 16 attack days no overall excess was noted, yet a 10% increase in out-of-hospital deaths occurred.Likely explanations for the initial increase in mortality include acute emotional stress coupled with breathing difficulties induced by gas masks and extended stay in sealed rooms with resultant hypoxia in susceptible individuals. Women were more vulnerable than men. The absence of elevated total mortality in the subsequent attacks suggests a rapid adaptation to the circumstances surrounding the war. The policy of an unventilated sealed room may have been detrimental.
Randomised double blind controlled clinical trial of intranasal budesonide in treatment of hay fever.
Authors: A W Cameron, I M Stanley, H J Wright
Journal: BMJ (1984)

The effectiveness of budesonide, a new non-halogenated glucocorticoid administered by nasal inhaler, was evaluated in a double blind comparison with placebo in patients presenting with hay fever. Patients were supplied with antihistamine tablets and eye drops for use when they considered that their symptoms were inadequately controlled by their inhaler. Patients recorded the severity of their symptoms in a daily diary card and visited their general practitioner for assessment weekly for four weeks. All nasal symptoms of hay fever were appreciably reduced in the group taking budesonide and, although their eye symptoms were more severe than in the group taking placebo, they did not use appreciably more eye drops than the latter. The placebo group used appreciably more antihistamine tablets than those in the budesonide group. No patients were withdrawn from the budesonide group because of treatment failure or unacceptable side effects. The results suggest that budesonide is an acceptable and effective treatment for the nasal symptoms of hay fever.
Audit of 26 years of obstetrics in general practice.
Authors: G. N. Marsh, D. M. Channing
Journal: BMJ (1989)

To assess the feasibility and quality of general practitioner obstetrics an audit of 1223 consecutive obstetric deliveries over 26 years was carried out with standard clinical records. The perinatal mortality of 9.0 per 1000 births was significantly better than the national average of about 19.0 per 1000 for the overall period. During the audit home deliveries virtually stopped. The proportion of consultant bookings and deliveries more than doubled because of more stringent booking arrangements despite relocation of the previously isolated general practitioner unit to beneath the consultant unit. Abnormal deliveries also rose significantly. A "steady state" was achieved during the final 11 years in which 73% of women booked to be delivered by their general practitioner, 64% were admitted to the general practitioner unit, and 54% were delivered by their general practitioner. Though this is enough to sustain obstetric experience, the proportion might safely be increased.
The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome
Authors: Mohammed Sebaihia, Brendan W Wren, Peter Mullany, Neil F Fairweather, Nigel Minton, Richard Stabler, Nicholas R Thomson, Adam P Roberts, Ana M Cerdeño-Tárraga, Hongmei Wang, Matthew TG Holden, Anne Wright, Carol Churcher, Michael A Quail, Stephen Baker, Nathalie Bason, Karen Brooks, Tracey Chillingworth, Ann Cronin, Paul Davis, Linda Dowd, Audrey Fraser, Theresa Feltwell, Zahra Hance, Simon Holroyd, Kay Jagels, Sharon Moule, Karen Mungall, Claire Price, Ester Rabbinowitsch, Sarah Sharp, Mark Simmonds, Kim Stevens, Louise Unwin, Sally Whithead, Bruno Dupuy, Gordon Dougan, Bart Barrell, Julian Parkhill
Journal: Nature Genetics (2006)
Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study
Authors: Dilip R. Karnad, Rakesh Bhadade, Pradeep K. Verma, Nivedita D. Moulick, Mradul K. Daga, Neelima D. Chafekar, Shivakumar Iyer
Journal: Intensive Care Medicine (2014)

Ulinastatin, a serine protease inhibitor, inhibits several pro-inflammatory proteases and decreases inflammatory cytokine levels and mortality in experimental sepsis. We studied the effect of ulinastatin on 28-day all-cause mortality in a double-blind trial in patients with severe sepsis in seven Indian hospitals.Patients with sepsis were randomized within 48 h of onset of one or more organ failures to receive intravenous administration of ulinastatin (200,000 IU) or placebo 12 hourly for 5 days.Of 122 randomized subjects, 114 completed the study (55 receiving ulinastatin, 59 receiving placebo). At baseline, the mean APACHE II score was 13.4 (SD = 4.4), 48 (42 %) patients were receiving mechanical ventilation, 58 (51 %) were on vasopressors, and 35 % had multiple organ failure. In the modified intention-to-treat analysis (patients receiving six or more doses of study drugs), 28-day all-cause mortality was 7.3 % with ulinastatin (4 deaths) versus 20.3 % (12 deaths) with placebo (p = 0.045). On multivariate analysis too, treatment with ulinastatin (odds ratio 0.26, 95 % CI 0.07-0.95; p = 0.042) independently decreased 28-day all-cause mortality. However, the mortality difference did not reach statistical significance in the intention-to-treat analysis [10.2 % (6/59 deaths) with ulinastatin versus 20.6 % (13/63 deaths) in the placebo group; p = 0.11]. The ulinastatin group had lower incidence of new-onset organ failure (10 vs. 26 patients, p = 0.003), more ventilator-free days (mean ± SD 19.4 ± 10.6 days vs. 10.2 ± 12.5 days, p = 0.019), and shorter hospital stay (11.8 ± 7.1 days vs. 24.2 ± 7.2 days, p < 0.001).In this pilot study, intravenous administration of ulinastatin reduced mortality in patients with severe sepsis in the modified intention-to-treat analysis, but not in the intention-to-treat analysis.
Comparison of Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography in Women With Suspected Coronary Artery Disease From the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) Trial
Authors: John P. Greenwood, Manish Motwani, Neil Maredia, Julia M. Brown, Colin C. Everett, Jane Nixon, Petra Bijsterveld, Catherine J. Dickinson, Stephen G. Ball, Sven Plein
Journal: Circulation (2013)

Coronary artery disease is the leading cause of death in women, and underdiagnosis contributes to the high mortality. This study compared the sex-specific diagnostic performance of cardiovascular magnetic resonance (CMR) and single-photon emission computed tomography (SPECT).A total of 235 women and 393 men with suspected angina underwent CMR, SPECT, and x-ray angiography as part of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) study. CMR comprised adenosine stress/rest perfusion, cine imaging, late gadolinium enhancement, and magnetic resonance coronary angiography. Gated adenosine stress/rest SPECT was performed with (99m)Tc-tetrofosmin. For CMR, the sensitivity in women and men was similar (88.7% versus 85.6%; P=0.57), as was the specificity (83.5% versus 82.8%; P=0.86). For SPECT, the sensitivity was significantly worse in women than in men (50.9% versus 70.8%; P=0.007), but the specificities were similar (84.1% versus 81.3%; P=0.48). The sensitivity in both the female and male groups was significantly higher with CMR than SPECT (P<0.0001 for both), but the specificity was similar (P=0.77 and P=1.00, respectively). For perfusion-only components, CMR outperformed SPECT in women (area under the curve, 0.90 versus 0.67; P<0.0001) and in men (area under the curve, 0.89 versus 0.74; P<0.0001). Diagnostic accuracy was similar in both sexes with perfusion CMR (P=1.00) but was significantly worse in women with SPECT (P<0.0001).In both sexes, CMR has greater sensitivity than SPECT. Unlike SPECT, there are no significant sex differences in the diagnostic performance of CMR. These findings, plus an absence of ionizing radiation exposure, mean that CMR should be more widely adopted in women with suspected coronary artery disease.http://www.controlled-trials.com. Unique identifier: ISRCTN77246133.
A Double-Blind Randomized Controlled Trial Comparing Sodium Tetradecyl Sulphate and Ethanolamine Oleate in the Sclerotherapy of Bleeding Oesophageal Varices
Authors: A. C. W. Chan, S. C. S. Chung, J. Y. Sung, J. W. C. Leung, A. K. C. Li
Journal: Endoscopy (1993)

The efficacy and side effects of 3 % sodium tetradecyl sulphate (STD) and 5 % ethanolamine oleate (ETH) were compared in 95 patients admitted with variceal bleeding. The patients were allocated in a randomised fashion to one of the treatment groups when varices were identified which were either actively bleeding or had signs of recent haemorrhage. Endoscopic examination was performed within 24 hours of admission. The endoscopist had no knowledge of which sclerosant was used. Intravariceal injections of 2 ml aliquots up to a maximum of 20 ml were made in a double-blinded manner. Repeat injections were performed at weekly intervals until all oesophageal varices were obliterated. Bleeding was successfully controlled in 42/48 (87.5 %) patients in the STD group and 41/47 (87.2 %) patients in the ETH group after one session of therapy. Variceal obliteration was achieved after 3.3 ± 1.3 sessions of STD and 4.5 ± 1.9 sessions of ETH (p < 0.05 Student's t-test). Post-injection pyrexia was significantly more common in the STD group (42 % vs 30 % p < 0.05, chi-square test). There was no difference in the rates of subsequent oesophageal ulceration, stricture formation or perforation of the oesophagus. It is concluded that STD and ETH are both effective in controlling variceal haemorrhage, but STD obliterates the varices in significantly fewer sessions.
Chlorotoxin bound magnetic nanovector tailored for cancer cell targeting, imaging, and siRNA delivery
Authors: Omid Veiseh, Forrest M. Kievit, Chen Fang, Ni Mu, Soumen Jana, Matthew C. Leung, Hyejung Mok, Richard G. Ellenbogen, James O. Park, Miqin Zhang
Journal: Biomaterials (2010)
Electrode Catheters and the Diagnostic Application of Intracardiac Electrography in Small Children
Authors: HAMISH WATSON
Journal: Circulation (1964)

The history of intracardiac electrography has been reviewed with particular reference to its practical application. The increasing versatility of electrode catheters is stressed and a new multipurpose diagnostic catheter with a platinum electrode is described. Electrograms chosen from 500 consecutive cases have been presented to demonstrate the use of an intracardiac lead during routine cardiac catheterization, and the special value of this technic in the investigation of congenital heart disease in babies and small children is emphasized.
Trypanosoma cruzi: in vitro induction of macrophage microbicidal activity.
Authors: N Nogueira, Z A Cohn
Journal: The Journal of Experimental Medicine (1978)

Normal, resident and inflammatory mouse peritoneal macrophages can be induced to display microbicidal activity against trypomastigotes of Trypanosoma cruzi by exposure to products from antigen-pulsed, sensitized spleen cell populations. Optimal macrophage microbicidal activity was achieved by constant exposure and daily renewal of the spleen cell factors. Macrophages obtained after an intraperitoneal injection of mild inflammatory agents were rapidly induced, displaying trypanocidal activity 24 h after exposure to the active spleen cell factor(s), and by 48 h, parasites were no longer observed. Resident peritoneal macrophages required 24 h longer for activation. Removal of the factor(s) before achieving complete disappearance of intracellular parasites led to resumed growth of the surviving organisms. The spleen cell factor(s) is effective when added either before or after exposure of the macrophages to trypomastigotes, and does not itself alter parasite viability. Dilution of the factor(s) up to 1:16 still results in significant trypanocidal activity. In vivo activated cells, obtained after a specific secondary challenge of animals infected with T. cruzi or Bacille Calmette-Guérin, lose their trypanocidal activity under in vitro conditions. This loss of activity can be prevented or restored by the addition of the active spleen cell factor(s). Induction of trypanocidal activity is also obtained with products from Concanavalin A- or lipopolysaccharide-stimulated normal spleen cells.
Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background
Authors: Qisheng Tu, Min Pi, Gerard Karsenty, Leigh Simpson, Shiguang Liu, L. Darryl Quarles
Journal: Journal of Clinical Investigation (2003)

To understand the role of the calcium-sensing receptor (CasR) in the skeleton, we used a genetic approach to ablate parathyroid glands and remove the confounding effects of elevated parathyroid hormone (PTH) in CasR-deficient mice. CasR deficiency was transferred onto the glial cells missing 2–deficient (Gcm2-deficient) background by intercrossing CasR- and Gcm2-deficient mice. Superimposed Gcm2 deficiency rescued the perinatal lethality in CasR-deficient mice in association with ablation of the parathyroid glands and correction of the severe hyperparathyroidism. In addition, the double homozygous CasR- and Gcm2-deficient mice demonstrated healing of the abnormal mineralization of cartilage and bone associated with CasR deficiency, indicating that rickets and osteomalacia in CasR-deficient mice are not due to an independent function of CasR in bone and cartilage but to the effect of severe hyperparathyroidism in the neonate. Analysis of the skeleton of 6-week-old homozygous CasR- and Gcm2-deficient mice also failed to identify any essential, nonredundant role for CasR in regulating chondrogenesis or osteogenesis, but further studies are needed to establish the function of CasR in the skeleton. In contrast, concomitant Gcm2 and CasR deficiency failed to rescue the hypocalciuria in CasR-deficient mice, consistent with direct regulation of urinary calcium excretion by CasR in the kidney. Double Gcm2- and CasR-deficient mice provide an important model for evaluating the extraparathyroid functions of CasR.
WHO's head calls on donors to do more to protect poor countries' health systems
Authors: J. Zarocostas
Journal: BMJ (2010)

The head of the World Health Organization is urging international donors and governments to increase funds to prevent the collapse of health systems in poor countries and to cease poaching locally trained health workers.

Margaret Chan told ministers attending the annual World Health Assembly this week in Geneva, “International donors, partners, and governments themselves have failed to rally around national health policies and strategies. This contributes to fragmentation, duplication, and added demands and costs and defeats national ownership.

“How can we scale up interventions or aim for universal coverage when health systems in so many countries are on the …
Multiple functions of a glioblastoma fusion oncogene
Authors: Ivan Babic, Paul S. Mischel
Journal: Journal of Clinical Investigation (2013)

RNA sequencing facilitates the discovery of novel gene fusions in cancer. In this issue of the JCI, Parker et al. identify an FGFR3-TACC3 fusion oncogene in glioblastoma and demonstrate a novel mechanism of pathogenicity. A miR-99a binding site within the 3′–untranslated region (3′-UTR) of FGFR3 is lost, releasing FGFR3 signaling from miR-99a–dependent inhibition and greatly enhancing tumor progression relative to WT FGFR3. These results provide compelling insight into the pathogenicity of a novel fusion oncogene and suggest new therapeutic approaches for a subset of glioblastomas.
<scp>l</scp> -Arginine Normalizes Coronary Vasomotion in Long-Term Smokers
Authors: Roxana Campisi, Johannes Czernin, Heiko Schöder, James W. Sayre, Heinrich R. Schelbert
Journal: Circulation (1999)

Background —Noninvasive measurements of myocardial blood flow (MBF) with PET revealed an abnormal coronary vasomotor response to cold pressor test in healthy long-term smokers. If coronary endothelial dysfunction accounted for this abnormality, we hypothesized that it could be reversed by l -arginine as the substrate for NO synthase. Methods and Results —MBF was quantified with 13 N-labeled ammonia and PET in 11 healthy smokers (age, 45±10 years; 27±10 years of smoking) and in 12 age-matched nonsmokers on 2 separate days. On day 1, MBF was measured at rest and, after intravenous l -arginine, during cold pressor test. On day 2, MBF was measured during cold pressor test and then at rest during l -arginine. Baseline rate-pressure product (RPP) (6559±1590 versus 7144±1157 bpm×mm Hg) and MBF (0.65±0.14 versus 0.73±0.13 mL · g −1 · min −1 ) were similar in nonsmokers and smokers. Cold pressor test increased RPP similarly in both groups (53±26% versus 46±26%), whereas MBF increased in nonsmokers (to 0.93±0.25 mL · g −1 · min −1 ; P &lt;0.05) but not in smokers (0.80±0.16 mL · g −1 · min −1 ). The percent MBF increase differed between nonsmokers and smokers (44±25% versus 11±14%; P =0.0017). However, after l -arginine, the magnitude of MBF response to cold pressor test no longer differed between groups (48±36% versus 48±28%), whereas RPP again increased similarly in the 2 groups (59±30% versus 44±16%). l -Arginine had no effect on resting MBF in smokers or nonsmokers. Conclusions —Our findings implicate the coronary endothelium as the major site of the abnormal vasomotor response in long-term smokers. Cold pressor test combined with PET imaging may allow the noninvasive identification of coronary endothelial dysfunction in humans.
Screening chromosome ends for learning disability
Authors: Samantha J L Knight, Jonathan Flint
Journal: BMJ (2000)

Learning disability affects about 3% of the population, yet the cause remains unknown in about 40% of people with moderate to severe learning disability (IQ<50) and in 70% of people with mild developmental delay (IQ 50-75).1 It is estimated that between 30% and 50% of cases of undiagnosed learning disability may be genetic in origin.2 Mapping and sequencing the human genome have provided new ways of looking for chromosomal abnormalities. The standard investigation for learning disability is to stain chromosomes to reveal their unique banding pattern and then to look for any anomalies using light microscopy. However, the resolution of this routine cytogenetic approach is limited since very small rearrangements are not visible and larger abnormalities escape notice if they occur in regions where the banding pattern is not distinctive. There have been many attempts to increase …