tbuckley/cabot-search huggingface dataset:
The role of high frequency oscillatory ventilation in acute respiratory distress syndrome
Authors: Christopher Gubran, Darryl Braganza-Menezes
Journal: Thorax (2013)

The role of high frequency oscillatory ventilation in acute respiratory distress syndromeThe OSCAR trial randomised acute respiratory distress syndrome (ARDS) patients to either high frequency oscillatory ventilation (HFOV) or conventional ventilatory support.This UK multicentre study recruited 795 patients between 2007 and 2012 who met established diagnostic criteria for ARDS and were expected to require ventilation for at least 2 days.Those with prior prolonged mechanical ventilation (>7 days), obstructive lung disease and recent pulmonary surgery were excluded.The primary outcome measure was all-cause mortality at 30 days postrandomisation.No statistically significant difference in 30-day mortality was observed between the patient cohorts.The primary outcome occurred in 41.7% (166/398) of the HFOV group and 41.1% (163/397) of the conventional ventilation group.Furthermore, there was no significant difference between the groups for length of ITU and hospital stay, antibiotic use or vasopressors and inotropic support.HFOV was associated with an increased use of neuromuscular blocking agents.The recently published OSCILLATE study, demonstrated inhospital mortality rates of 47% versus 35% ( p=0.005) for HFOV and conventional ventilation, respectively.OSCILLATE suggested harm from early use of HFOV in ARDS.Both OSCAR and OSCILLATE therefore contrast to previous meta-analysis suggesting benefit of HFOV in ARDS patients.The OSCAR study failed to show superiority of HFOV over conventional methods.Conversely, HFOV did not cause harm.The median duration of HFOV in OSCAR was 3 days and a more prolonged treatment may be necessary to demonstrate the mortality benefit.Certainly on current evidence, HFOV cannot be recommended as initial or routine care in ARDS.
Autophagy Is Activated in Colorectal Cancer Cells and Contributes to the Tolerance to Nutrient Deprivation
Authors: Kazunori Sato, Katsuya Tsuchihara, Satoshi Fujii, Masanori Sugiyama, Tomoyuki Goya, Yutaka Atomi, Takashi Ueno, Atsushi Ochiai, Hiroyasu Esumi
Journal: Cancer Research (2007)

Several types of cancer cells, including colorectal cancer-derived cell lines, show austerity, the resistance to nutrient starvation, but exactly how cancer cells obtain energy sources under conditions in which their external nutrient supply is extremely limited remains to be clarified. Because autophagy is a catabolic process by which cells supply amino acids from self-digested organelles, cancer cells are likely to use autophagy to obtain amino acids as alternative energy sources. Amino acid deprivation-induced autophagy was assessed in DLD-1 and other colorectal cancer-derived cell lines. The autophagosome-incorporated LC3-II protein level increased after treatment with a combination of autolysosome inhibitors, which interferes with the consumption of autophagosomes. Autophagosome formation was also morphologically confirmed using ectopically expressed green fluorescent protein-LC3 fusion proteins in DLD-1 and SW480 cells. These data suggest that autophagosomes were actively produced and promptly consumed in colorectal cancer cells under nutrient starvation. Autolysosome inhibitors and 3-methyl adenine, which suppresses autophagosome formation, remarkably enhanced apoptosis under amino acid-deprived and glucose-deprived condition. Similar results were obtained in the cells with decreased ATG7 level by the RNA interference. These data suggest that autophagy is pivotal for the survival of colorectal cancer cells that have acquired austerity. Furthermore, autophagosome formation was seen only in the tumor cells but not in the adjacent noncancerous epithelial cells of colorectal cancer specimens. Taken together, autophagy is activated in colorectal cancers in vitro and in vivo, and autophagy may contribute to the survival of the cancer cells in their microenvironment.
Histamine-induced coronary spasm in regions of intimal thickening in miniature pigs: roles of serum cholesterol and spontaneous or induced intimal thickening.
Authors: K Egashira, H Tomoike, Y Yamamoto, A Yamada, Y Hayashi, M Nakamura
Journal: Circulation (1986)

The pathogenesis of histamine-induced coronary spasm was examined angiographically and morphometrically in Göttingen miniature pigs. In five of 36 consecutive pigs that were 4 to 5 months of age, coronary spasm was provoked by the intracoronary administration of histamine, and the left coronary arteries were examined histologically without endothelial denudation (group 1). Endothelial balloon denudation of the major branch of the left coronary artery was performed in 31 of 36 pigs and five died during the procedure. The remaining 26 pigs were randomly allotted to one of two groups, one fed a cholesterol-supplemented (group 2, n = 13) and one fed a regular low-cholesterol diet (group 3, n = 13). After 3 months, serum cholesterol increased significantly from 57 +/- 6 to 222 +/- 27 mg/dl (p less than .01) in group 2, but remained unchanged (48 +/- 5 to 55 +/- 6 mg/dl) in group 3. Percent narrowing of the coronary diameter induced by 10 micrograms/kg ic histamine after administration of the H2 blocker cimetidine (60 mg/kg iv) was 39 +/- 3% and 24 +/- 2% (p less than .05 between groups 2 and 3) at the nondenuded site and 78 +/- 3% and 74 +/- 4% at the denuded site in groups 2 and 3, respectively (p less than .01 between nondenuded and denuded sites). Histamine-induced percent narrowing of the coronary diameter after cimetidine in group 1, 2, and 3 pigs correlated well with the degree of intimal thickness on an exponential curve (r = .92, p less than .001). Since percent narrowing at the intact site was 27% (n = 19) in all three groups, predicted histamine-induced percent narrowing at the spastic site, applying the geometric theory, was 33 +/- 3%. Accordingly, enhanced constriction of the coronary artery with intimal thickening in response to histamine can largely be explained by the acquired hyperresponsiveness of the vascular wall to autacoids. This phenomena, not related to the level of serum cholesterol, may be uniquely linked to the basic pathology of evolution of atherosclerosis.
STUDIES ON THE ENZYMES OF PNEUMOCOCCUS
Authors: O. T. Avery, Glenn E. Cullen
Journal: The Journal of Experimental Medicine (1920)

1. Pneumococci contain an intracellular enzyme or enzymes which (a) hydrolyze to some extent intact protein and (b) hydrolyze with striking avidity peptones. The optimum reaction for hydrolysis is pH 7 to 7.8, which also represents the optimum for the growth of pneumococcus. For convenience the terms "protease" and "peptonase" have been used, but no assumption is made as to whether the two actions, proteolysis and peptolysis, are due to two separate enzymes or are two activities of the same enzyme. 2. Solutions of intracellular substance of comparable enzymic activity may be prepared by dissolving the bacteria in bile, in sodium choleate, or by mechanical and autolytic disintegration of the cell. 3. The rapidity with which peptone is hydrolyzed is proportional to the concentration of the enzyme. 4. Heating the enzyme for 10 minutes at 100 degrees C. destroys its activity. 5. Increasing the acidity to pH 5, the acid death-point of pneumococcus, suspends activity but does not destroy the enzyme, for activity is restored by readjustment to pH 7.8. 6. Attenuation of virulence to 1/1,000,000 of the original virulence had no measurable quantitative effect on the enzyme activity.
Our genomes today: time to be clear
Authors: Jeantine E Lunshof, Madeleine P Ball
Journal: Genome Medicine (2013)

DNA is an identifier. We are not defined by our genome, but our DNA is ours and we can be identified through it. Despite the comments made at the time, it was neither wicked nor tacky when Craig Venter, shortly after the first human genome sequence was published in 2001, publicly revealed that he was one donor of the samples used in Celera's genome sequencing project [1]. Venter later explained that by identifying himself as a donor he had intended to demystify the human genome and to reduce public fears about the potential misuse of genetic information [2].
Endotoxin impairs biliary glutathione and HCO3? excretion and blocks the choleretic effect of nitric oxide in rat liver
Authors: M Trauner, M H Nathanson, S A Rydberg, T A Koeppel, C Gartung, W C Sessa, J L Boyer
Journal: Hepatology (1997)

Cholestasis in patients with sepsis has been attributed to the effects of endotoxin (lipopolysaccharides, LPS) and LPS-induced cytokines, which are also potent stimulators of systemic and hepatic nitric oxide (NO) synthesis. NO donors stimulate bile acid-independent bile flow in normal rat liver, but the effects of LPS-induced NO on bile formation remain unclear. To address this question we examined the effects of NO and its mediator guanosine 3′,5′-cyclic monophosphate (cGMP) on bile flow and biliary HCO 3 − and glutathione excretion in isolated perfused rat livers (IPRL) from LPS-treated rats. Portal and systemic NO2- + NO3- plasma levels were increased 47-fold in LPS-treated rats and were also elevated in perfusate (6-fold) and bile (9-fold) after isolating and perfusing livers from these animals. Bile flow, HCO 3 − , and glutathione output were decreased by 33%, 25%, and 81% in these IPRL, respectively. Stimulation of NO synthesis with L-arginine or inhibition of inducible NO synthesis with aminoguanidine did not change bile flow, although pretreatment with aminoguanidine inhibited NO production by 85%. Moreover, the choleretic effects of infusions of the NO donors sodium nitroprusside (SNP) and S-nitroso-acetyl-penicillamine were markedly reduced in endotoxemic IPRL compared with normal controls, and SNP-induced HCO 3 − and glutathione excretion were reduced by 61% and 86%, respectively. SNP-induced cyclic GMP production was 2.3-fold lower than in normals, but the choleretic effect of dibutyryl cGMP was only slightly reduced in endotoxemic livers. These findings indicate that LPS reduces bile acid-independent bile flow primarily by inhibiting biliary excretion of glutathione and to a lesser extent HCO 3 − , whereas LPS-induced NO does not modulate bile formation in endotoxemia. Thus, impairment of the major determinants of bile acid-independent bile flow by LPS may contribute significantly to the pathogenesis of the cholestasis of sepsis.
Amino acid and peptide absorption after proximal small intestinal resection in the rat.
Authors: A B Garrido, H J Freeman, Y C Chung, Y S Kim
Journal: Gut (1979)

In experimental animals with massive proximal intestinal resection, in vivo ileal absorption of an amino acid mixture containing L-leucine and glycine as well as two different dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. Both amino acid and dipeptide absorption were markedly enhanced in the ileal segments. However, the absorption rates from the two perfused dipeptides differed. L-leucine absorption from L-leucyl-glycine was much greater than from glycyl-L-leucine. Brush border amino-peptidase activities after resection were also increased but dissociation between absorption and hydrolytic activity occurred. This study indicates that certain dipeptides are handled differently by adapting ileal segments. Furthermore, the changes observed probably reflect mucosal cellular hyperplasia occurring in association with intestinal adaptation.
P110 Fluticasone propionate/formoterol fumarate combination therapy is more efficacious in improving lung function than its individual components in patients with asthma
Authors: D. Price, A. Papi, K. Kaiser, B. Grothe, M. Lomax, T. McIver
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Combination therapy with an inhaled corticosteroid (ICS) and a long-acting ß<sub>2</sub>-agonist (LABA) is the most effective treatment option for patients with asthma uncontrolled with ICS monotherapy.1 In practice, asthma symptoms remain uncontrolled or only partly controlled in many patients. A new therapy option for asthma combining the ICS fluticasone propionate (FLUT) and the LABA formoterol fumarate (FORM) in a single aerosol inhaler (FLUT/FORM; <b><i>flutiform</i></b><sup>®</sup>), has been developed at doses of 100/10, 250/10 and 500/20 μg for twice-daily administration. In this analysis, data were pooled from up to five randomised, double-blind, parallel-group studies in order to assess the efficacy of FLUT/FORM in terms of improvement in lung function (as indicated by change in FEV<sub>1</sub>). <h3>Methods</h3> The analysis included adults and adolescents with a range of asthma severities who were treated for 8 or 12 weeks with FLUT/FORM (100/10, 250/10 or 500/20 μg twice daily) or the equivalent nominal dose of FLUT monotherapy (100, 250 or 500 μg twice daily; five studies) or FORM monotherapy (10 μg twice daily; three studies). <h3>Results</h3> FLUT/FORM was associated with a significantly greater improvement in lung function, as indicated by change in FEV<sub>1</sub>, compared with its individual components (Abstract P110 table 1). FLUT/FORM was superior to FORM with regard to change in pre-dose FEV<sub>1</sub> from baseline to study end; the least-squares (LS) mean difference for FLUT/FORM vs FORM was 0.13 l (95% CI 0.07 to 0.19; p&lt;0.001). Similarly, FLUT/FORM was superior to FLUT with regard to change in FEV<sub>1</sub> from pre-dose at baseline to 2 h post-dose at study end (LS mean difference FLUT/FORM vs FLUT 0.15 L [95% CI 0.10 to 0.19; p&lt;0.001]). <h3>Conclusions</h3> The combination of fluticasone/formoterol in a single aerosol inhaler is more effective than fluticasone or formoterol given alone in improving lung function for patients with a range of asthma severities.
Dietary Intake of n-6 Fatty Acids Modulates Effect of Apolipoprotein A5 Gene on Plasma Fasting Triglycerides, Remnant Lipoprotein Concentrations, and Lipoprotein Particle Size
Authors: Chao-Qiang Lai, Dolores Corella, Serkalem Demissie, L. Adrienne Cupples, Xian Adiconis, Yueping Zhu, Laurence D. Parnell, Katherine L. Tucker, Jose M. Ordovas
Journal: Circulation (2006)

Background— Apolipoprotein A5 gene ( APOA5 ) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association. Methods and Results— We investigated the interaction between APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant-like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and 1147 women who were Framingham Heart Study participants. Polymorphisms −1131T&gt;C and 56C&gt;G, representing 2 independent haplotypes, were analyzed. Significant gene–diet interactions between the −1131T&gt;C polymorphism and polyunsaturated fatty acid (PUFA) intake were found ( P &lt;0.001) in determining fasting TGs, RLP concentrations, and particle size, but these interactions were not found for the 56C&gt;G polymorphism. The −1131C allele was associated with higher fasting TGs and RLP concentrations ( P &lt;0.01) in only the subjects consuming a high-PUFA diet (&gt;6% of total energy). No heterogeneity by sex was found. These interactions showed a dose-response effect when PUFA intake was considered as a continuous variable ( P &lt;0.01). Similar interactions were found for the sizes of VLDL and LDL particles. Only in carriers of the −1131C allele did the size of these particles increase (VLDL) or decrease (LDL) as PUFA intake increased ( P &lt;0.01). We further analyzed the effects of n-6 and n-3 fatty acids and found that the PUFA–APOA5 interactions were specific for dietary n-6 fatty acids. Conclusions— Higher n-6 (but not n-3) PUFA intake increased fasting TGs, RLP concentrations, and VLDL size and decreased LDL size in APOA5 −1131C carriers, suggesting that n-6 PUFA–rich diets are related to a more atherogenic lipid profile in these subjects.
Magnetic Targeting Enhances Engraftment and Functional Benefit of Iron-Labeled Cardiosphere-Derived Cells in Myocardial Infarction
Authors: Ke Cheng, Tao-Sheng Li, Konstantinos Malliaras, Darryl R. Davis, Yiqiang Zhang, Eduardo Marbán
Journal: Circulation Research (2010)

Rationale : The success of cardiac stem cell therapies is limited by low cell retention, due at least in part to washout via coronary veins. Objective : We sought to counter the efflux of transplanted cells by rendering them magnetically responsive and imposing an external magnetic field on the heart during and immediately after injection. Methods and Results : Cardiosphere-derived cells (CDCs) were labeled with superparamagnetic microspheres (SPMs). In vitro studies revealed that cell viability and function were minimally affected by SPM labeling. SPM-labeled rat CDCs were injected intramyocardially, with and without a superimposed magnet. With magnetic targeting, cells were visibly attracted toward the magnet and accumulated around the ischemic zone. In contrast, the majority of nontargeted cells washed out immediately after injection. Fluorescence imaging revealed more retention of transplanted cells in the heart, and less migration into other organs, in the magnetically targeted group. Quantitative PCR confirmed that magnetic targeting enhanced cell retention (at 24 hours) and engraftment (at 3 weeks) in the recipient hearts by ≈3-fold compared to nontargeted cells. Morphometric analysis revealed maximal attenuation of left ventricular remodeling, and echocardiography showed the greatest functional improvement, in the magnetic targeting group. Histologically, more engrafted cells were evident with magnetic targeting, but there was no incremental inflammation. Conclusions : Magnetic targeting enhances cell retention, engraftment and functional benefit. This novel method to improve cell therapy outcomes offers the potential for rapid translation into clinical applications.
Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge.
Authors: B S Bender, T Croghan, L Zhang, P A Small
Journal: The Journal of Experimental Medicine (1992)

To investigate the role of CD8+ T lymphocytes in recovery from influenza pneumonia, we used transgenic mice either homozygous (-/-) or heterozygous (+/-) for beta 2-microglobulin (beta 2-M) gene disruption. These mice lack major histocompatibility complex-restricted class I (CD8+) T cells. We found that after challenge with a nonlethal influenza virus, the beta 2-M (-/-) mice had significantly delayed pulmonary viral clearance. Furthermore, after challenge with a more virulent influenza virus, the beta 2-M (-/-) mice had a significantly higher mortality rate than did control mice. Thus, CD8+ T cells are important in recovery from virulent influenza infections, but other host defense mechanisms can clear the respiratory tract of more benign infections.
On the existence and location of cardiac mucosa: an autopsy study in embryos, fetuses, and infants
Authors: G De Hertogh, P Van Eyken, N Ectors, J Tack, K Geboes
Journal: Gut (2003)

The incidence of gastric cardiac adenocarcinoma has increased in the last decades. Gaining insight into the pathogenesis of this lesion is hampered by the limited knowledge of the origin and histology of cardiac mucosa (CM). Currently, the location, extent, and even the existence of CM are controversial.We studied the development of the gastro-oesophageal junction (GOJ) in embryos, fetuses, and infants to clarify if CM is a normal structure at birth and where it is located.Twenty one autopsy cases were evaluated ranging in age from 13 weeks' gestational age (GA) to seven months.The distal oesophagus and proximal part of the stomach were embedded entirely. Serial sections were stained with haematoxylin-eosin and alcian blue/periodic acid-Schiff. The following parameters were measured: length of abdominal oesophagus; length of columnar lined oesophagus; length of CM; and distance from CM to angle of His.CM was present in all evaluated sections. Its mean length varied throughout gestation. A maximum value was reached at a GA of 16 weeks (1.2 mm). After term delivery it was very short (0.3-0.6 mm). CM was proximal to, or straddled, the angle of His in all cases. During gestation, the mucin staining pattern of the CM was to a high degree similar to that of the developing pyloric mucosa.CM develops during pregnancy and is present at birth as a normal structure. If the angle of His is taken as a landmark for the GOJ, CM is located in the distal oesophagus.
Photoactivation of Endogenous Latent Transforming Growth Factor–β1 Directs Dental Stem Cell Differentiation for Regeneration
Authors: Praveen R. Arany, Andrew Cho, Tristan D. Hunt, Gursimran Sidhu, Kyungsup Shin, Eason Hahm, George X. Huang, James Weaver, Aaron Chih-Hao Chen, Bonnie L. Padwa, Michael R. Hamblin, Mary Helen Barcellos-Hoff, Ashok B. Kulkarni, David J. Mooney
Journal: Science Translational Medicine (2014)

Low-power laser–activated endogenous latent transforming growth factor–β1 (LTGF-β1) directs resident dental stem cell differentiation to promote dentin regeneration.
Primary cutaneous actinomycosis.
Authors: A Aulaqi
Journal: BMJ (1977)

Bruising in thyrotoxicosis SIR,-I wish to report briefly the case of a woman with long-standing thyrotoxicosis whose presenting complaint was of bruising in order to inquire whether similar patients have been encountered.The patient, aged 47, was suspected of having thyrotoxicosis some four years before hospital consultation, which was delayed because, although her goitre and eye signs were typical, she had lost very little weight.However, in this time she had started to bruise spontaneously and often exces- sively on the limbs.Her serum thyrosine con- centration was elevated at 245 nmol (19 ,ug 100 ml) and her 4-h radioiodine tracer uptake was 48 ".The platelet count was 180 109,l (180 000lmm:1) and her prothrombin time and other coagulation tests normal.The factor VIII level was 1-5 g/l and that of factor IX 1 1 g,l.The antinuclear factor and latex tests were negative.
Relapse Risk after Discontinuation of Risperidone in Alzheimer's Disease
Authors: D.P. Devanand, Jacobo Mintzer, Susan K. Schultz, Howard F. Andrews, David L. Sultzer, Danilo de la Pena, Sanjay Gupta, Sylvia Colon, Corbett Schimming, Gregory H. Pelton, Bruce Levin
Journal: New England Journal of Medicine (2012)

Among patients with Alzheimer's disease who have had a response to antipsychotic medication for psychosis or agitation–aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established.