tbuckley/cabot-search huggingface dataset:
Diets that differ in their FODMAP content alter the colonic luminal microenvironment
Authors: Emma P Halmos, Claus T Christophersen, Anthony R Bird, Susan J Shepherd, Peter R Gibson, Jane G Muir
Journal: Gut (2014)

<h3>Objective</h3> A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial. <h3>Design</h3> Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed. <h3>Results</h3> Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs 9.83 (9.72 to 9.93) log<sub>10</sub> copies/g; p&lt;0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing <i>Clostridium</i> cluster XIVa (median ratio 6.62; p&lt;0.001) and mucus-associated <i>Akkermansia muciniphila</i> (19.3; p&lt;0.001), and reduced <i>Ruminococcus torques</i>. <h3>Conclusions</h3> Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation. <h3>Trial registration number</h3> ACTRN12612001185853.
Standardization of Medical Records
Authors: M. S. Harrison
Journal: BMJ (1965)

maximum suppression of plasma cortisol.We have found this dosage of methopyrapone satisfactory in the evaluation of pituitary- corticotrophin reserve.Finally, the diagnosis of isolated corticotrophin deficiency in our patient does not rest solely on the lack of response to metho- pyrapone.We feel sure that Dr. Sprunt will agree that both the correction of insulin- induced hypoglycaemia-unresponsiveness with exogenous corticotrophin and the low-normal plasma cortisol during fever further support the presence of a hypothalamic-pituitary defect affecting the secretion of corticotrophin.-We are, etc.,
Systemic upregulation of neutrophil α-defensins and serine proteases in neutrophilic asthma
Authors: Katherine Baines, Jodie Simpson, Lisa Wood, Rodney Scott, Peter Gibson
Journal: European Respiratory Journal (2011)

Background:  The well-characterised airway inflammatory phenotypes of asthma include eosinophilic, neutrophilic, mixed eosinophilic/neutrophilic and paucigranulocytic asthma, defined by the proportion of sputum granulocytes. Systemic inflammation is now recognised as an important part of some airway diseases, but the role of systemic inflammation in the pathogenesis of asthma phenotypes remains unknown.   Methods:  Induced sputum samples and peripheral blood were collected from participants with asthma (n=36). Airway inflammatory cell counts were performed on induced sputum and inflammatory phenotype assigned based on the airway eosinophil and neutrophil cutoffs of 3% and 61% respectively. Gene expression profiles were generated (Illumina Humanref-8 V3) from whole blood RNA and analysed using GeneSpring GX11.   Results:  There were 6 genes classified as differentially expressed between the 4 asthma phenotypes including the α-defensins ( DEFA ) 1, 1B, 3 and 4, neutrophil proteases cathepsin G (CTSG) and elastase (ELA2). Systemic expression of  DEFA1, 1B, 3, 4, CTSG  and  ELA2  was significantly higher in the neutrophilic asthma phenotype. Microarray results were successfully validated using real-time PCR. Plasma elastase was significantly elevated in people with neutrophilic airway inflammation.   Conclusion:  There is systemic upregulation of α-defensin and neutrophil protease expression in neutrophilic asthma, which may represent pro-inflammatory effects on the bone marrow and the release of immature neutrophils into the circulation. This demonstrates a systemic inflammatory component in neutrophilic asthma that further differentiates this from other asthma phenotypes, and indicates different mechanisms.
Crosslinking of ANCA-antigens stimulates superoxide release by human neutrophils.
Authors: R Kettritz, J C Jennette, R J Falk
Journal: Journal of the American Society of Nephrology (1997)

Anti-neutrophil cytoplasmic antibodies (ANCA) activate primed human polymorphonuclear neutrophils (PMN) in vitro, resulting in a respiratory burst and degranulation. In this study, the hypotheses that the initiation of this process requires engagement of the F(ab')2 portion of ANCA, and that crosslinking of ANCA target antigens is necessary to trigger superoxide (O2-) release, were explored. It is speculated that Fc gamma receptor engagement is a modulator of ANCA-mediated activation. Flow cytometry demonstrated that intact human ANCA immunoglobulin (Ig), their corresponding F(ab')2 and Fab fragments, as well as a murine monoclonal to human PR3 and its F(ab')2 fragment, bind to ANCA antigens on the surface of PMN primed with tumor necrosis factor (TNF) alpha. Intact Ig of patients with PR3-ANCA or with MPO-ANCA stimulate O2- release from TNF alpha-primed normal PMN (2.6 +/- 3.57 to 15.3 +/- 7.39 nmol O2-/2.5 x 10(6) PMN/30 min). Corresponding F(ab')2 fragments result in similar O2- production (10.2 +/- 4.34 to 36.9 nmol) in a dose-dependent manner. ANCA Fab fragments do not stimulate O2- generation until these fragments are crosslinked with F(ab')2 of goat anti-human Ig F(ab')2, or when fragments are biotinylated and crosslinked with avidin. In contrast with these human autoantibody data, a mouse monoclonal anti-human PR3 antibody (25.7 +/- 8.55 nmol O2-), but not its corresponding F(ab')2 fragment, activates TNF alpha-treated human PMN. When the Fc gamma IIa receptors were blocked, superoxide production was reduced by 33% using human PR3-ANCA Ig (P < 0.05). In conclusion, PMN activation by ANCA occurs when intact ANCA or ANCA F(ab')2 fragments crosslink target antigens on the neutrophil cell surface. ANCA F(ab') fragments result in PMN activation when crosslinked by secondary reagents.
The relevance of biologics for the treatment of patients with psoriasis
Authors: Peter C.M. van de Kerkhof
Journal: British Journal of Dermatology (2009)

Journal Article The relevance of biologics for the treatment of patients with psoriasis Get access Peter C.M. Van De Kerkhof Peter C.M. Van De Kerkhof Department of Dermatology, Radboud University Medical Centre, PO box 9100, Nijmegen 6500HB, the Netherlands E‐mail: p.vandekerkhof@derma.umcn.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 6, 1 December 2009, Pages 1213–1214, https://doi.org/10.1111/j.1365-2133.2009.09499.x Published: 01 December 2009
Ventilation heterogeneity is associated with asthma control in adults
Authors: Claude Farah, Sue Downie, Jessica Kermode, Nathan Brown, Kate Hardaker, Gregory King, Norbert Berend, Cheryl Salome
Journal: European Respiratory Journal (2011)

Background:  The clinical relevance of increased ventilation heterogeneity, a marker of small airways disease, in asthma is unclear. Ventilation heterogeneity is an independent determinant of airway hyperresponsiveness, improves with bronchodilators and inhaled corticosteroids (ICS), and worsens during exacerbations but its relationship to asthma control is unknown.   Objective:  To determine the association between ventilation heterogeneity and current asthma control before and after ICS treatment.   Methods:  Asthmatic subjects had the 5-item symptom-only asthma control questionnaire (ACQ 5 ) and lung function measured at baseline and after 3 months of high dose ICS treatment. Ventilation heterogeneity was measured as S cond  and S acin  by multiple breath nitrogen washout. S cond  and S acin  represent ventilation heterogeneities in small airways where gas transport occurs mainly by convection or diffusion, respectively. Spearman correlations and paired t-tests were performed.   Results:  At baseline (n=110, 64 female), ACQ 5  correlated with S cond  (r s  = 0.30, p=0.002) and S acin  (r s  = 0.21, p=0.03). After treatment (n=55), the mean (SD) ACQ 5  improved (1.31 (0.71) to 0.70 (0.77), p cond  improved (0.068 (0.035) to 0.053 (0.033) L -1 , p acin  did not significantly change (0.147 (0.07) to 0.142 (0.06) L -1 , p=0.28). The change in ACQ 5  correlated with changes in S cond  (r s  = 0.34, p=0.02) and S acin  (r s  = 0.33, p=0.01).   Conclusions:  Current asthma control is associated with markers of small airways disease. Improvements in ventilation heterogeneity with anti-inflammatory therapy are associated with improvements in symptoms. Sensitive measures of small airway function may be useful in monitoring therapy in asthma.
Decreased exercise blood pressure in older adults after exercise training: contributions of increased fitness and decreased fatness
Authors: B B Barone, N-Y Wang, A C Bacher, K J Stewart
Journal: British Journal of Sports Medicine (2008)

To describe the contribution of changes in fitness and fatness resulting from exercise training on changes in submaximal exercise blood pressure (BP) during treadmill testing.Prospective, randomised, controlled trial.Sedentary older adults (n = 115) with untreated prehypertension or mild hypertension.Six-month supervised aerobic and strength training.Systolic BP (SBP) was assessed at rest and during each stage of a maximal graded exercise test (GXT) that determined Vo(2)peak. General and regional fatness was assessed by anthropometry, dual-energy x-ray absorptiometry and MRI. BP changes were calculated for each GXT stage, and multivariate regression models were used to describe the association of changes in exercise BP with changes in fitness and fatness.After training, exercisers versus controls had significantly increased Vo(2)peak and significantly lower measures of general and regional fatness. Also, stage-specific SBP was significantly lower at stage 3 (-9.4 vs -1.6 mm Hg, p = 0.03) and stage 4 (-7.9 vs -1.2 mm Hg, p = 0.03). Pooled regression analysis across all stages showed that exercisers had a 7.1 mm Hg reduction in SBP, but this reduction fell short of statistical significance (p = 0.12) compared with controls. A 1.0 ml/kg/min increase in Vo(2)peak and a 1.0 cm decrease in waist circumference independently predicted a 1.0 mm Hg decrease in exercise SBP (p = 0.04 and p = 0.001, respectively).Decreased exercise SBP was independently associated with decreased waist circumference, a marker of abdominal obesity and increased fitness. These findings suggest that exercise training improves multiple factors that have an independent influence on SBP.
Is It Ethical for Patients with Renal Disease to Purchase Kidneys from the World's Poor?
Authors: Tarif Bakdash, Nancy Scheper-Hughes
Journal: PLoS Medicine (2006)

In many countries, the number of patients waiting for a kidney transplant is increasing. But there is a widespread and serious shortage of kidneys for transplantation, a shortage that can lead to suffering and death. One approach to tackling the shortage is for a patient with renal disease to buy a kidney from a living donor, who is often in a developing country, a sale that could--in theory at least--help to lift the donor out of poverty. Such kidney sales are almost universally illegal. Proponents of kidney sales argue that since the practice is widespread, it would be safer to formally regulate it, and that society should respect people's autonomous control over their bodies. Critics express concern about the potential for exploitation and coercion of the poor, and about the psychological and physical after-effects on the donors of this illegal kidney trade.
Ink4a/Arf loss promotes tumor recurrence following Ras inhibition
Authors: M. W. VanBrocklin, J. P. Robinson, K. J. Lastwika, A. J. McKinney, H. M. Gach, S. L. Holmen
Journal: Neuro-Oncology (2011)

Aberrant activation of rat sarcoma (Ras) signaling contributes to the development of a variety of human cancers, including gliomas. To determine the dependence of high-grade gliomas on continued Ras signaling, we developed a doxycycline-regulated Kirsten Ras (KRas) glioma mouse model. We previously demonstrated that KRas is required for the maintenance of glioblastoma multiforme tumors arising in the context of activated Akt signaling in vivo; inhibition of KRas expression resulted in apoptotic tumor regression and significantly increased survival. We utilized a well-established glioma mouse model to determine the reliance of gliomas on continued KRas signaling in the context of Ink4a/Arf deficiency, a common occurrence in human gliomas. Despite the dependency of primary gliomas on continued KRas signaling, a significant percentage of tumors progressed to a KRas-independent state in the absence of Ink4a/Arf expression, demonstrating that these tumor suppressors play a critical role in the suppression of glioma recurrence. While even advanced stages of gliomas may remain dependent upon KRas signaling for maintenance and growth, our findings demonstrate that loss of Ink4a/Arf facilitates the acquisition of oncogene independence and tumor recurrence. Furthermore, reactivation of the Ras mitogen-activated protein kinase pathway in the absence of virally delivered KRas expression is a common mechanism of recurrence in this context.
Sputum induction with inhaled mannitol in children
Authors: Gerardo Vizmanos-Lamotte, Elisa Canturri Gispert, Víctor Núñez Eroles, Mireia Martínez Abelló, Joan Martínez Benazet, Antonio Moreno-Galdó
Journal: European Respiratory Journal (2015)

Mannitol is used as an indirect challenge test to assess airway hyperresponsiveness in asthmatic adults and children as young as 4 years old [1–4]. Recently, it has been tested with success in adults as a sputum inducer [5, 6]. In children, induced sputum is usually obtained by hypertonic saline solution (HSS) and has several indications, such as sample obtaining in infectious diseases [7], monitoring severe asthma [8] and defining asthma phenotypes [9]. Acceptable induced sputum samples can be obtained in healthy and asthmatic children using the mannitol challenge test <http://ow.ly/KSd2M>
Seasonal Pattern of Acute Myocardial Infarction in the National Registry of Myocardial Infarction
Authors: Joseph P. Ornato, Mary Ann Peberdy, Nisha C. Chandra, David E. Bush
Journal: Journal of the American College of Cardiology (1996)

The purpose of this study was to determine whether the rate of hospital admission for acute myocardial infarction (AMI) varies seasonally in a large, prospective U.S. registry. Identification of specific patterns in the timing of the onset of AMI is of importance because it implies that there are triggers external to the atherosclerotic plaque. Using death certificate data, most investigators have noted a seasonal pattern to the death rate from AMI. However, it is unclear whether this observation is due to variation in the prevalence of AMI or to other factors that may alter the likelihood of a fatal outcome. We examined the seasonal mean number of cases of AMI (adjusted for the length of days in each season) that were submitted to the National Registry of Myocardial Infarction (NRMI) by 138 high volume core hospitals over a 3-year period (December 21,1990 through December 20,1993) during which the number of hospitals participating in the Registry was stable. Data were analyzed using general linear modeling and analysis of variance. High volume core hospitals reported 83,541 cases of AMI to the Registry during the study period. Approximately 10% more such cases were entered into the Registry in winter or spring than in summer (p < 0.05). The same trends were seen in both northern and southern states, men and women, patients <70 versus ≥70 years of age and those with Q wave versus non-Q wave AMI. We conclude that there is a seasonal pattern to the reporting rate of cases of AMI in the NRMI. This observation further supports the hypothesis that acute cardiovascular events may be triggered by events that are external to the atherosclerotic plaque.
Strong Smooth Muscle Differentiation Is Dependent on Myocardin Gene Amplification in Most Human Retroperitoneal Leiomyosarcomas
Authors: Gaëlle Pérot, Josette Derré, Jean-Michel Coindre, Franck Tirode, Carlo Lucchesi, Odette Mariani, Laure Gibault, Louis Guillou, Philippe Terrier, Alain Aurias
Journal: Cancer Research (2009)

Myocardin (MYOCD), a serum response factor (SRF) transcriptional cofactor, is essential for cardiac and smooth muscle development and differentiation. We show here by array-based comparative genomic hybridization, fluorescence in situ hybridization, and expression analysis approaches that MYOCD gene is highly amplified and overexpressed in human retroperitoneal leiomyosarcomas (LMS), a very aggressive well-differentiated tumor. MYOCD inactivation by shRNA in a human LMS cell line with MYOCD locus amplification leads to a dramatic decrease of smooth muscle differentiation and strongly reduces cell migration. Moreover, forced MYOCD expression in three undifferentiated sarcoma cell lines and in one liposarcoma cell line confers a strong smooth muscle differentiation phenotype and increased migration abilities. Collectively, these results show that human retroperitoneal LMS differentiation is dependent on MYOCD amplification/overexpression, suggesting that in these well-differentiated LMS, differentiation could be a consequence of an acquired genomic alteration. In this hypothesis, these tumors would not necessarily derive from cells initially committed to smooth muscle differentiation. These data also provide new insights on the cellular origin of these sarcomas and on the complex connections between oncogenesis and differentiation in mesenchymal tumors.
Nitric oxide and mitochondrial respiration in the heart
Authors: G BROWN, V BORUTAITE
Journal: Cardiovascular Research (2007)

Nitric oxide (NO) inhibits the mitochondrial respiratory chain, resulting in inhibition of ATP production, increased oxidant production and increased susceptibility to cell death. NO reversibly binds to the oxygen binding site of cytochrome oxidase, reacting either with the oxidised copper to give inhibitory nitrite, or with the reduced haem, resulting in reversible inhibition in competition with oxygen. Because of this competition, NO may sensitise tissues to hypoxia. NO, or derivative N2O3 or S-nitrosothiols, may inactivate complex I by S-nitrosation. Peroxynitrite (ONOO−) inhibits mitochondrial respiration at multiple sites, and also causes mitochondrial permeability transition. Inhibition of mitochondrial respiration by NO and its derivatives stimulates production of reactive oxygen and nitrogen species by mitochondria, which have signalling roles in the heart, but may also contribute to cell death. In the heart, NO is produced by endothelial NO synthase (eNOS) in endothelium and caveolae of cardiomyocytes, by neuronal NO synthase (nNOS) in sarcoplasmic reticulum and possibly mitochondria, and under pathological situations by inducible NO synthase (iNOS) in the sarcoplasm. Haemoglobin and myoglobin may have multiple roles in determining oxygen and NO gradients within the heart, which may remove NO at high oxygen, but possibly supply it at low oxygen. Stimulating or inhibiting NOS in the heart has been found to cause small changes in heart oxygen consumption in vivo; however, it is still unclear whether these changes are due to direct NO inhibition of mitochondrial respiration or indirect actions of NO. NO inhibition of mitochondrial respiration is likely to be more important in the heart during hypoxia and/or pathologies where iNOS is expressed.
Type of Vegetarian Diet, Body Weight, and Prevalence of Type 2 Diabetes
Authors: Serena Tonstad, Terry Butler, Ru Yan, Gary E. Fraser
Journal: Diabetes Care (2009)

We assessed the prevalence of type 2 diabetes in people following different types of vegetarian diets compared with that in nonvegetarians.The study population comprised 22,434 men and 38,469 women who participated in the Adventist Health Study-2 conducted in 2002-2006. We collected self-reported demographic, anthropometric, medical history, and lifestyle data from Seventh-Day Adventist church members across North America. The type of vegetarian diet was categorized based on a food-frequency questionnaire. We calculated odds ratios (ORs) and 95% CIs using multivariate-adjusted logistic regression.Mean BMI was lowest in vegans (23.6 kg/m(2)) and incrementally higher in lacto-ovo vegetarians (25.7 kg/m(2)), pesco-vegetarians (26.3 kg/m(2)), semi-vegetarians (27.3 kg/m(2)), and nonvegetarians (28.8 kg/m(2)). Prevalence of type 2 diabetes increased from 2.9% in vegans to 7.6% in nonvegetarians; the prevalence was intermediate in participants consuming lacto-ovo (3.2%), pesco (4.8%), or semi-vegetarian (6.1%) diets. After adjustment for age, sex, ethnicity, education, income, physical activity, television watching, sleep habits, alcohol use, and BMI, vegans (OR 0.51 [95% CI 0.40-0.66]), lacto-ovo vegetarians (0.54 [0.49-0.60]), pesco-vegetarians (0.70 [0.61-0.80]), and semi-vegetarians (0.76 [0.65-0.90]) had a lower risk of type 2 diabetes than nonvegetarians.The 5-unit BMI difference between vegans and nonvegetarians indicates a substantial potential of vegetarianism to protect against obesity. Increased conformity to vegetarian diets protected against risk of type 2 diabetes after lifestyle characteristics and BMI were taken into account. Pesco- and semi-vegetarian diets afforded intermediate protection.
Mechanism of action and delivery possibilities for TGFβ1 in the treatment of myocardial ischemia
Authors: P HERMONAT, D LI, B YANG, J MEHTA
Journal: Cardiovascular Research (2007)

Myocardial ischemia-reperfusion (IR) injury is associated with structural alterations involving both the necrotic and the non-necrotic myocardium. These changes are referred to as myocardial remodeling. In addition to the loss of critical cardiomyocyte mass through cell death, there are further structural alterations associated with scarring, as well as changes in a family of endogenous enzymes, the matrix metalloproteases (MMP), which cause loss of myocardial extracellular matrix (ECM) [Janssens S, Lijnen HR. What has been learned about cardiovascular effects of matrix metalloproteinases from mouse models. Cardiovasc Res 2006;69:585–594., Wainwright CL. Matrix metalloproteinases, oxidative stress and the acute response to acute myocardial ischaemia and reperfusion. Curr Opin Pharmacol 2004;4:132–138.]. The chemokine TGFβ1, which has wide-ranging effects upon cells and tissues, is showing promise as a useful drug/agent for the limitation of IR injury. Coupled with the identification of TGFβ1 as a therapeutic agent for IR treatment are investigations into its mode of delivery to the patient. Gene therapy utilizing delivery by viral vectors is just one of many possible ways to deliver TGFβ1 for IR treatment. In this review we discuss the mechanisms of action of TGFβ1 and how it might be delivered successfully to patients under risk of or who are actively undergoing acute IR injury.
A SIMPLE METHOD OF TREATING CLUB-FOOT: (Congenital Talipes Equino-varus)
Authors: A. S. B. Bankart
Journal: BMJ (1922)

rmKD?aLJowl I115 exhaustion, for wlicih stimulants were given, followed by the hypodermic administration of digitalin and strychnine.For several hours the patient was extremely ill.' The right arLn