tbuckley/cabot-search huggingface dataset:
S7 Adiposity and asthma, pulmonary function and atopy in 11-year old children: a birth cohort study
Authors: R. Wang, A. Custovic, A. Simpson, L. Lowe, C. S. Murray
Journal: Thorax (2011)

<h3>Background</h3> Results of studies investigating the association between obesity and asthma, atopy and lung function have been inconsistent, in part due to the limitation of BMI in evaluating body adiposity. <h3>Objectives</h3> To investigate the association between obesity and asthma, wheeze, atopy, lung function and bronchial hyper-responsiveness in children at age 11 years using bioelectrical impedance (BIA) and BMI. <h3>Methods</h3> Children from the unselected birth cohort study attending follow-up at age 11 years had percent body fat (PBF) and truncal fat (PTF) assessed using BIA (Tanita BC-418). Weight and height were also measured. Current asthma and wheeze were derived from a validated respiratory questionnaire. Atopy was ascertained using skin prick testing. Lung function was assessed using spirometry and bronchial hyper-responsiveness by 5-step methacholine challenge according to ATS guidelines. <h3>Results</h3> 646 children (339 male) completed anthropometric measurements. BMI z-score, PBF and PTF were associated with current wheeze (OR [95% CI]: 1.27 [1.03 to 1.57], p=0.03; 1.04 [1.00, 1.08], p=0.04; 1.04 [1.00, 1.08], p=0.04 respectively). BMI z-score, PBF and PTF were also associated with current asthma (1.30 [1.04 to 1.63], p=0.02; 1.04 [1.00 to 1.08], p=0.06; 1.04 [1.00 to 1.08], p=0.04). However, the effect of PBF and PTF appeared strongest in girls (PBF: 1.12 [1.04 to 1.20], p=0.004; PFT: 1.11[1.04 to 1.20], p=0.003; p=0.05 and p=0.04 for interactions respectively). Children were defined as normal or overweight according to BMI (23% overweight) and PBF (29.8% overweight) cut-offs; overweight children had an increased risk of asthma (BMI: 1.73 [0.99 to 3.02], p=0.05; PBF: 2.09 [1.23 to 3.32] p=0.006). This was highly significant in girls (BMI: 3.34 [1.43 to 7.83], p=0.005; PBF: 4.74 [1.98 to 11.35], p&lt;0.001; p=0.05 and p=0.02 for interactions respectively). Increasing BMI was associated with increases in both FEV<sub>1</sub> and FVC but reductions in FEV<sub>1</sub>: FVC ratios. This association was again stronger in girls than boys. No associations between adiposity and atopy or bronchial hyper-responsiveness were found. <h3>Conclusion</h3> Higher BMI z-score, PBF and PTF were associated with increased risks of wheeze and asthma. This effect was stronger in girls. BIA measurements appeared to have stronger associations in girls with outcomes than BMI. This may reflect the ability of BIA to measure adiposity more accurately than BMI.
Survival After Implantable Cardioverter-Defibrillator Implantation in the Elderly
Authors: Derek Yung, David Birnie, Paul Dorian, Jeffrey S. Healey, Christopher S. Simpson, Eugene Crystal, Andrew D. Krahn, Yaariv Khaykin, Douglas Cameron, Zhongliang Chen, Douglas S. Lee
Journal: Circulation (2013)

Background— The benefit of implantable cardioverter-defibrillators (ICDs) among elderly patients is controversial and may be attenuated by nonarrhythmic death. We examined the impact of age on device-delivered therapies and outcomes after primary or secondary prevention ICD. Methods and Results— In a prospective, inclusive registry of 5399 ICD recipients in Ontario, Canada (February 2007 to September 2010), device-delivered therapies and complications were determined at routine clinic visits. Among primary prevention ICD recipients aged 18 to 49 (n=317), 50 to 59 (n=769), 60 to 69 (n=1336), 70 to 79 (n=1242), and ≥80 (n=275) years, mortality increased with age, as follows: 2.1, 3.0, 5.4, 6.9, and 10.2 deaths per 100 person-years, respectively ( P &lt;0.001). Secondary prevention ICD recipients aged 18 to 49 (n=114), 50 to 59 (n=244), 60 to 69 (n=481), 70 to 79 (n=462), and ≥80 (n=159) years also exhibited increasing mortality, as follows: 2.2, 3.8, 6.1, 8.7, and 15.5 deaths per 100 person-years, respectively ( P &lt;0.001). However, rates of appropriate shock were similar across age groups: from 6.7 (18–49 years) to 4.2 (≥80 years) per 100 person-years after primary prevention ICDs ( P =0.139) and from 11.4 (18–49 years) to 11.9 (≥80 years) per 100 person-years after secondary prevention ICDs ( P =0.993). Covariate-adjusted competing risk analysis demonstrated higher risk of death ( P trend &lt;0.001 for both primary and secondary prevention) but no significant decline in appropriate shocks with older age after primary ( P =0.130) or secondary ( P =0.810) prevention ICD implantation. Conclusions— Whereas elderly patients exhibited increased mortality after ICD implantation, rates of appropriate device shocks were similar across age groups. Decisions regarding ICD candidacy should not be based on age alone but should consider factors that predispose to mortality despite defibrillator implantation.
Pathological effects of Phaseolus vulgaris isolectins on pig jejunal mucosa in organ culture.
Authors: M J Kik, J F Koninkx, A van den Muysenberg, F Hendriksen
Journal: Gut (1991)

The interaction of plant lectins with pig small intestinal epithelium in organ culture was studied. The binding of Phaseolus vulgaris (PHA) isolectins E4 and L4 to the microvilli and microvillus vesicles in the top area of the villi was shown by immunoelectron microscopy. Differences were observed in the distribution of the isolectins. In the explants cultured for five hours with the PHA isolectins, the enterocyte height and the villus length were decreased, and a lower villus: crypt ratio was calculated. Ultrastructurally, the microvilli were shorter and irregularly positioned. After incubation with both PHA E4 and PHA L4, clusters of small vesicles, tied off from the microvilli, were seen in higher numbers when compared with control explants. The activity of the brush border enzyme sucrase-isomaltase was reduced in the PHA E4 incubated explants but did not change in the PHA L4 incubated explants. This investigation shows that explants of pig jejunal mucosa in organ culture are suitable for study of the pathological effects of lectins on the small intestinal mucosa. This method may also be used in elucidating the mechanisms by which damage to mucosal structure occurs.
TCT-636 Use Of Optical Coherence Tomography To Study The Role Of Non-Compliant Balloon Post-Dilation In Optimization Of Bioresorbable Vascular Scaffolds
Authors: Jaya Chandrasekhar, Aun-Yeong Chong, Michael Froeschl, Christopher Glover, Alexander Dick, Jean-Francois Marquis, Michel R. Le May, Marino Labinaz, Derek So
Journal: Journal of the American College of Cardiology (2014)
Abstract 3105: Chromosome 18q encodes a chromosomal instability suppressor locus in colorectal cancer
Authors: Rebecca A. Burrell, Sarah E. McClelland, David Endesfelder, Andrew Rowan, Arne Schenk, Michal Sheffer, Nadeem Shaikh, Enric Domingo, Maik Kschischo, Eytan Domany, Julian Downward, Ian Tomlinson, Charles Swanton
Journal: Cancer Research (2012)

Abstract Identifying molecular mechanisms initiating Chromosomal Instability (CIN) may lead to approaches to limit intratumour heterogeneity and treatment failure in cancer. Here we identify candidate CIN-suppressor genomic loci that are subject to copy number loss in CIN colorectal cancers (CRCs). Genes encoded within CIN-suppressor loci were characterized through an RNA interference screen for induction of chromosome segregation errors in mitosis, revealing 5 CIN-suppressor genes encoded on chromosome 18q. CIN-suppressor gene silencing in chromosomally stable cells generates structurally abnormal chromosomes, which are missegregated during mitosis. A chromosome segregation error spectrum characteristic of structurally abnormal chromosomes is also observed in CIN CRC cell lines. 18q loss occurs in the majority of aneuploid CRCs, and is associated with both structural and numerical instability in colorectal tumours, and with aneuploidy onset in a rare carcinoma-in-adenoma dataset. These data support a role for chromosome 18q in the maintenance of chromosomal structural integrity and mitotic fidelity, and suggest that 18q copy number loss may initiate CIN during CRC development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3105. doi:1538-7445.AM2012-3105
Objectively Measured Physical Activity and Its Association With Adiponectin and Other Novel Metabolic Markers
Authors: Brad S. Metcalf, Alison N. Jeffery, Joanne Hosking, Linda D. Voss, Naveed Sattar, Terence J. Wilkin
Journal: Diabetes Care (2008)

OBJECTIVE—Recent evidence suggests that, in children, traditional markers of metabolic disturbance are related only weakly to physical activity. We therefore sought to establish the corresponding relationships with newer metabolic markers. RESEARCH DESIGN AND METHODS—This was a nonintervention longitudinal study of 213 healthy children recruited from 54 schools in Plymouth, U.K. MTI accelerometers were used to make objective 7-day recordings of physical activity at ages 5 ± 0.3 (mean ± SD), 6, 7, and 8 years. Overall physical activity was taken as the average of the four annual time points. The metabolic markers at 8 years were adiponectin, leptin, high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment). Potential confounders included percent body fat measured by dual-energy X-ray absorptiometry and diet measured by food frequency questionnaire. RESULTS—Whereas physical activity did not correlate with insulin resistance (r = −0.01), leptin (r = +0.04), or hsCRP (r = +0.01) independently of percent body fat, it did correlate with adiponectin, but inversely (r = −0.18, P = 0.02). This unexpected inverse relationship was strongest among the less active children (physical activity &amp;lt; median: r = −0.30, P = 0.01) but negligible in the more active children (physical activity &amp;gt; median: r = +0.04, P = 0.76). Adiponectin was significantly higher (0.52 SD, P &amp;lt; 0.01) in the least active tertile compared with the other two tertiles. Insulin resistance, however, did not differ across the physical activity tertiles (P = 0.62). CONCLUSIONS—Adiponectin levels in children are highest among those who are least active, but their insulin resistance is no different. Adiponectin has a known insulin-sensitizing effect, and our findings are consistent with a selective effect at low levels of physical activity.
Abstract 3556: New curcumin analogues are cytotoxic towards estrogen receptor negative human breast cancer cell lines
Authors: Babasaheb D. Yadav, Sebastien Taurin, Lesley Larsen, Rhonda J. Rosengren
Journal: Cancer Research (2010)

Abstract There is an urgent need for the development of a safe and efficacious drug therapy for the treatment of estrogen receptor negative breast cancers due to their high malignant nature and poor prognosis. In this study, a series of new heterocyclic monoketo curcumin analogues were synthesized and screened for anticancer activity. Among twenty eight analogues screened in estrogen receptor negative human breast cancer cell-lines MDA-MB-231 (ER-/HER2-), MDA-MB-468 (ER-/HER2-) and SKBr3(ER-/HER2+), the two most potent compounds were designated as RL-71 and RL-66. Cytotoxicity was assessed by sulforhodamine B (SRB) assay. Furthermore, the compounds were studied for their ability to modulate cell cycle progression and induce apoptosis. The mechanism of these drugs was also examined by determining protein expression by Western blot analysis. The results showed that RL-71 and RL-66 had sub micromolar EC50 values in all the cell lines and the cytotoxicity was concentration and time dependent. Mechanistic analyses demonstrated that RL-71 at 1µM and RL-66 at 2µM increased the proportion of MDA-MB-231 cells in G2/M-phase by 162.02 ± 1.53% and 134.12 ± 2.17% over control (P&amp;lt;0.001) respectively. In addition, the treatment with RL-71 (1µM) and RL-66 (2µM) increased the proportion of apoptotic MDA-MB-231 cells by 10-fold and 4-fold over control (p&amp;lt;0.001), respectively. Similar results were also produced in SKBr3 and MDA-MB-468 cells. Furthermore, Western blot analysis confirmed the effect of drugs on different cancer related genes involved in cell proliferation and apoptosis. Thus, these data suggest that the novel curcumin analogues RL-71 and RL-66 are potent antitumor drugs and have significant potential for further drug development for estrogen receptor negative breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3556.
Sensitivity of R-R Variation and Valsalva Ratio in Assessment of Cardiovascular Diabetic Autonomic Neuropathy
Authors: Armand H Rothschild, Clarice R Weinberg, Jeffrey B Halter, Daniel Porte, Michael A Pfeifer
Journal: Diabetes Care (1987)

R-R variation and the Valsalva ratio are commonly used to quantitatively assess diabetic autonomic neuropathy (DAN). To assess the sensitivity of these two measures to parasympathetic ablation, 12 nondiabetic subjects were tested before and after graded doses (0.3–4.0 mg i.v.) of atropine. R-R variation was significantly reduced at 0.7 mg, whereas Valsalva ratio was not significantly smaller until the 2.0-mg dose of atropine. R-R variation continued to become progressively smaller during the 0.85-, 1.0-, and 2.0-mg doses. Valsalva ratio, but not R-R variation, was further reduced by the 4.0- mg dose. To further compare these two measures, two groups of diabetic subjects were compared with a group of nondiabetic subjects (n = 22). One group of diabetic subjects had symptoms of DAN (n = 22), and the other diabetic group had no symptoms of DAN (n = 19). In DAN subjects, both R-R variation (nondiabetic 33.2 ± 4.3 vs. DAN 9.8 ± 1.2, P &amp;lt; .001) and the Valsalva ratio (nondiabetic 1.98 ± 0.07 vs. DAN 1.55 ± 0.07, P &amp;lt; .001) were reduced. However, in asymptomatic subjects, R-R variation (23.2 ± 3.9, P &amp;lt; .05), but not Valsalva ratio (1.94 ± 0.13, NS), was less than nondiabetic subjects. Even after p-blockade, R-R variation was still less in both groups of diabetic subjects (nondiabetic 34.4 ± 4.2 vs. DAN 7.4 ± 1.3, P &amp;lt; .001; asymptomatic 21.8 ± 3.3, P &amp;lt; .02). Thus, the reduced R-R variation is more likely due to decreased parasympathetic rather than increased sympathetic activity. We conclude that R-R variation is more sensitive than Valsalva ratio in detecting parasympathetic ablation and is useful for early detection and follow-up of mild autonomic dysfunction. Valsalva ratio may be more useful for sequential long-term evaluation in subjects with severe diabetic autonomic dysfunction, in whom R-R variation is maximally suppressed.
Does hypophosphatemia play a role in acute liver failure?
Authors: James P. Knochel
Journal: Hepatology (1989)

This is the first record of hypophosphataemia in acute liver failure induced by paracetamol; it occurred in most of the patients and was severe (&lt;0.3 mmol/l) in more than one third. At this level hypophosphataemia produces impaired oxygen transport and tissue hypoxia, abnormal leucocyte function, depressed platelet numbers and function, generalised muscle weakness, and disorder of the central nervous system; these are frequent complications of acute liver failure. The similarity of the effects of liver failure and hypophosphataemia on the central nervous system (irritability, muscle weakness, dysarthria, confusion, and coma) suggests that phosphate depletion may be important in hepatic encephalopathy, and a progressive defect of phosphate metabolism in brain tissue of patients with chronic liver disease was shown recently by nuclear magnetic resonance spectroscopy. The cause of hypophosphataemia in acute liver failure remains unclear. None of the recognised causes of moderate (0.3-0.7 mmol/l) hypophosphataemia correlated with the phosphate concentrations in our patients. The reduced maximum tubular reabsorption of phosphate in two patients suggests an increased loss of renal phosphate, perhaps due to a direct effect of paracetamol, although the correlation between plasma phosphate and creatinine concentrations suggests that renal failure may protect against hypophosphataemia. Because of the serious clinical implications of phosphate imbalance in acute liver failure the homoeostatic mechanisms of bone and renal phosphate reabsorption in this condition need to be studied urgently. Plasma phosphate concentrations should be monitored carefully during infusion of glucose in patients with liver failure.
Personal reflections on 25 years of immunodermatology
Authors: T.S. Kupper
Journal: British Journal of Dermatology (2014)

When I was invited by the British Association of Dermatologists to give the Rook Oration in 1999, the field of immunodermatology was enjoying a time of rapid evolution. We had just solved the structure of human cutaneous lymphocyte antigen (CLA) 2 years previously,1 and we were hard at work characterizing how the backbone of this structure, P selectin glycoprotein ligand‐1, was glycosylated by T cells destined to home to skin. My work over the previous 15 years had been focused on the production of cytokines by epidermal keratinocytes,2 3 4 5 6 culminating in the construction of transgenic mice that overexpressed cytokines under the control of keratin promoters,7 8 9 10 11 12 demonstrating that in vivo, keratinocyte cytokines could mediate inflammation and leucocyte recruitment. In the early 1980s, keratinocytes were still regarded as little more than the complex bricks and mortar of the epidermis, maintaining the barrier function of skin. Over the next decade it became clear that these cells could also participate in immune and inflammatory responses by elaborating cytokines, then a revolutionary idea.4 That an ‘activated epidermis’ could elaborate factors that would recruit leucocytes had never been previously considered, as Langerhans cells were thought to be the principal immunologically important cells in this tissue.13 We learned over the following years that keratinocyte cytokines could also influence the behaviour of dendritic cells, particularly as they efficiently present antigen to T cells.10 By the late 1990s, the participation of keratinocytes and other ‘innate immune’ cells in skin immunity had become accepted.6
The usefulness of competitive PCR: airway gene expression of IL-5, IL-4, IL-4delta2, IL-2, and IFNgamma in asthma
Authors: E M Glare, M Divjak, M J Bailey, E H Walters
Journal: Thorax (2001)

Background-Asthma has been described as an eosinophilic bronchitis driven by interleukin(IL)-4 and IL-5.The quantification of cytokine mRNA levels in airway samples has been confounded by housekeeping gene expression which diVers between and within asthmatics and controls.Methods-The usefulness of competitive reverse transcriptase-polymerase chain reaction (RT-PCR) that is independent of housekeeping gene expression for quantitating the mRNA for interferon (IFN) , IL-2, IL-5, IL-4 and its receptor antagonist encoding splicing variant IL-4 2 was determined in a cross sectional study of 45 normal control subjects and 111 with asthma.Results-Atopic controls and atopic asthmatic subjects expressed more IL-5 than non-atopic controls (p<0.02) in bronchoalveolar lavage (BAL) cells, but not in biopsy specimens.IL-5 mRNA expression in BAL cells from asthmatic subjects using inhaled corticosteroids (ICS) was significantly lower than those not receiving ICS (p=0.04).IL-2 mRNA levels diVered with steroid use in biopsy specimens but not in BAL cells.IFN , IL-4, and IL-4 2 mRNA levels did not diVer between any groups and were not aVected by steroid use.IL-4 and IL-4 2 mRNA levels were positively correlated (p<0.0001),suggesting coordinated transcription.Conclusions-While the signal diVerentiation of competitive PCR in asthma may rival that of in situ hybridisation and immunohistochemistry, the method is expensive and wasteful of material.
Comparison clinical study of the efficacy and safty of fluocinolone acetonide, hydroquinone and tretinoine vs hydroquinone and tretinoine for melasma treatment
Authors: Ortiz Y, Leon G, R.E. Benuto, H Muñoz, I Arellano, M.E. Arrocha, L Boeta, G Luna, M.L. Morales
Journal: Journal of the American Academy of Dermatology (2004)
Cauterization of the Cervix
Authors: A. Savill
Journal: BMJ (1938)

<h3>Abstract</h3> The Emx1-IRES-Cre transgenic mouse is commonly used to direct genetic recombination in forebrain excitatory neurons. However, the original study reported that Emx1-Cre is also expressed embryonically in peripheral autonomic ganglia, which could potentially affect the interpretation of targeted circuitry contributing to systemic phenotypes. Here, we report that Emx1-Cre is expressed in the afferent vagus nerve system involved in autonomic cardiorespiratory regulatory pathways. Our imaging studies revealed expression of Emx1-Cre driven tdtomato fluorescence in the afferent vagus nerve innervating the dorsal medulla of brainstem, cell bodies in the nodose ganglion, and their potential target structures at the carotid bifurcation such as the carotid sinus and the superior cervical ganglion (SCG). Photostimulation of the afferent terminals in the nucleus tractus solitarius (NTS) <i>in vitro</i> using Emx1-Cre driven ChR2 reliably evoked EPSCs in the postsynaptic neurons with electrophysiological characteristics consistent with the vagus afferent nerves. In addition, optogenetic stimulation targeting the Emx1-Cre expressing structures identified in this study, such as vagus nerve, carotid bifurcation, and the dorsal medulla surface transiently depressed cardiorespiratory rate in urethane anesthetized mice <i>in vivo</i>. Together, our study demonstrates that Emx1-IRES-Cre is expressed in the key peripheral autonomic nerve system and can modulate cardiorespiratory function independently of forebrain expression. These results raise caution when interpreting systemic phenotypes of Emx1-IRES-Cre conditional recombinant mice, and also suggest the utility of this line to investigate modulators of the afferent vagal system.
Regional and age-specific patterns of pandemic H1N1 influenza virus seroprevalence inferred from vaccine clinical trials, August-October 2009
Authors: T F Tsai, P Pedotti, A Hilbert, K Lindert, M Hohenboken, A Borkowski, N Groth, L J da Silva, M H Kyaw
Journal: Eurosurveillance (2010)

The extent of the H1N1 pandemic has been estimated from case counts and deaths but the proportion of exposed populations with inapparent infections has not been described in detail. We analysed haemagglutination-inhibition (HI) antibody titres of pre-vaccination sera from pandemic vaccine trials conducted in six countries on four continents to provide an indication of A/CA/07/2009(H1N1)-like influenza seroprevalence in those populations. Among 7,962 subjects, ranging in age from 12 months to over 60 years, the proportions with HI antibody titres > or =40 to the H1N1pnd virus in the period from August to October 2009 were, by country: Costa Rica 26.4%, United States (US) 22.5%, Switzerland 16.9%, Germany 12.6%, Belgium 10.1%, and Japan 5.9%. Age-specific seropositivity rates in the samples were higher in children and adolescents in Costa Rica and in the US than in Europe and in Japan. The low proportion of seropositive children in Europe and Japan suggests that little local viral transmission had occurred in those regions even as late as September and October 2009, while in the US and Costa Rica, the greater proportion of previously infected children and young adults suggested that a significant number of asymptomatic infections had occurred during the first pandemic wave. Nevertheless, in all locations, the majority of the population remained susceptible to the pandemic virus at the beginning of the influenza season in the northern hemisphere, justifying the implementation of public health interventions.