tbuckley/cabot-search huggingface dataset:
Amyloid P-component is a constituent of normal human glomerular basement membrane.
Authors: R F Dyck, C M Lockwood, M Kershaw, N McHugh, V C Duance, M L Baltz, M B Pepys
Journal: The Journal of Experimental Medicine (1980)

Glomerular and other vascular basement membranes were found to contain an antigen that was immunochemically indistinguishable from serum amyloid P-component. There was no immunological cross-reactivity between antisera to serum amyloid P-component and to collagen types I, III, IV, or V. The amyloid P-component antigen was confined to the endothelial aspect, the lamina rara interna, of glomerular basement membrane. It could not be eluted by high-ionic-strength saline, EDTA, dithiothreitol, or either polar or nonpolar detergents, but was released into solution when isolated glomerular basement membrane was digested by highly purified bacterial collagenase. Most of these P-component molecules and their constituent polypeptide chains were of higher molecular weight and lower isoelectric point than serum amyloid P-component. These findings indicate that, as well as being a normal plasma protein and a universal constituent of amyloid deposits, P-component is also a normal matrix glycoprotein of basement membrane in which it is covalently linked to collagen and/or other matrix proteins. This may be relevant both to the pathogenesis of amyloidosis and to other aspects of physiology and pathology of basement membranes.
CHRONIC INTESTINAL STASIS AND EPILEPSY
Authors: A. W. Robertson
Journal: BMJ (1924)

CHRONIC INTESTINAL STABIS AND EPILEPSY.'Ba 1191 accidents and finally succumbed.The post-mortem exam- ination showed a very -extensive cerebraI thrombosis.In enterio fever there are two accidents which it is often difficult to differentiate-perforation and haemorrhage.In the former a rise of blood pressure occurs after the primary shock, but in the latter the fall of blood pressure is always very marked and prolonged.In pneumonia a rise of blood pressure before the crisis is of.ten the first sign of some complication, while a fall may indicate impending heart failure.Finally, blood pressure observationi may be of considerable assistanice in cases of albuminuria, a high blood pressure inidicating renal disease-either a lnephritis or that type of renal damage which results from hyperpiesis or arterio- sclerosis.In pregnancy the sphygmomanometer may be especially helpful, for it is often difficult to decide how much importance should be attached to a small amounit of albumin in theiurine of a pregnant womani.The niormal svstolic pressure of a woman of about 30 of average plhysique is abcut 112 mm.Hg.A pressure of over 130 wvould suggest tlle need for careful and frequent examiniation, and a pressure of over 150 would probablv indicate the onset of eclampsia.I do niot think that a blood pressure of over 160 systolic or 90 diastolic is ever normal, although there are cases in which the diastolic pressure remains about 100 for a time witlhout any ascertainable cause, and then returniis to niormal limits.Excitement may cause such conisiderable rises of pressure that it is well to bear in mind the rule that a hiiglh pressure is of greater significance when accompanied by a slow pulse.
Chemical and physical properties of gall stones in South Australia: implications for dissolution treatment.
Authors: M J Whiting, B M Bradley, J M Watts
Journal: Gut (1983)

Of 406 consecutive patients with gall-bladder stones, 387 were treated by cholecystectomy and 19 were treated with chenodeoxycholic acid.The gall stones found in 356 of the 387 patients at operation were analysed chemically for cholesterol and calcium, physically for number, size, and mass, and radiologically before cholecystectomy for stone lucency.Gall stones rich in cholesterol (>80% by weight) were present in 75% of patients, while pigment stones (<25% cholesterol) were found in 12% of patients.Out of the 406 gall-stone patients, 77 (19%) had functioning gall bladders which contained radiolucent stones 1.5 cm or less in diameter, thereby fulfilling the criteria which are used by most clinicians in selecting patients for dissolution therapy of cholesterol gall stones.The stones of 61 of these patients were available for chemical analysis and 52 (85%) were rich in cholesterol.Using the more stringent criterion for stone size of 1 cm or less in diameter, only 11% of patients had stones suitable for dissolution treatment.Taking into account other factors such as lack of compliance with treatment, obesity, and calcium salts in gall stones, it appears that no more than 10% of gall-stone patients presenting to a general hospital could be successfully treated with chenodeoxycholic acid.
Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling
Authors: Jennifer E. Ho, Wei-Yu Chen, Ming-Huei Chen, Martin G. Larson, Elizabeth L. McCabe, Susan Cheng, Anahita Ghorbani, Erin Coglianese, Valur Emilsson, Andrew D. Johnson, Stefan Walter, Nora Franceschini, Christopher Joseph O'Donnell, Abbas Dehghan, Chen Lu, Daniel Levy, Christopher Holmes Newton-Cheh, Honghuang Lin, Janine F. Felix, Eric R. Schreiter, Ramachandran S. Vasan, James Louis Januzzi, Richard Theodore Lee, Thomas Wang
Journal: Journal of Clinical Investigation (2013)

The suppression of tumorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response when bound to its ligand, IL-33. The other isoform is a soluble protein (sST2) that is thought to be a decoy receptor for IL-33 signaling. Elevated sST2 levels in serum are associated with an increased risk for cardiovascular disease. We investigated the determinants of sST2 plasma concentrations in 2,991 Framingham Offspring Cohort participants. While clinical and environmental factors explained some variation in sST2 levels, much of the variation in sST2 production was driven by genetic factors. In a genome-wide association study (GWAS), multiple SNPs within IL1RL1 (the gene encoding ST2) demonstrated associations with sST2 concentrations. Five missense variants of IL1RL1 correlated with higher sST2 levels in the GWAS and mapped to the intracellular domain of ST2, which is absent in sST2. In a cell culture model, IL1RL1 missense variants increased sST2 expression by inducing IL-33 expression and enhancing IL-33 responsiveness (via ST2L). Our data suggest that genetic variation in IL1RL1 can result in increased levels of sST2 and alter immune and inflammatory signaling through the ST2/IL-33 pathway.
Ovariotomy during Pregnancy
Authors: E. H. May
Journal: BMJ (1893)

far overtaxed lhospitality of tle JOURNAL, and ask attention to the accompanying woodcut froimi an untouclhed plhotograph taken thlree months after operation.The case now briefly reported is that of an unmarried American missionary lady, aged 26, whlo, without any history of local injury, noticed, in February, 1892, a nodule, the size of a large bean, in the lower external quadrant of the righlt breast.There was no family hiistory of any significance.Menstruation lhad been established at 14, and the periods lhad ever since been in every respect normal.Shle was seen on May 12th, 1893, when, in the position indicated, a smootlh, somewhat elastic, splherical tumour, perfectly movable, about the size of a large walnut, was perceptible about lhalf way tlhrouglh the dept I of the gland.It was sliglhtly sensitive to pressure; it underwent no change of any kind during menstruation, but, independently of thlis, had lately become the seat of severe paroxysmal pain, lasting for a couple of hours at a time, and then disappearing completely for seven days.Nipple and areola normal.In the lower hemisphere of the left breast there were a number of small, lhard, indolent nodules, evidently lobules of the gland.The-e disappeared
Evidence-Based Guidelines for Determination of Sample Size and Interpretation of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30
Authors: Kim Cocks, Madeleine T. King, Galina Velikova, Marrissa Martyn St-James, Peter M. Fayers, Julia M. Brown
Journal: Journal of Clinical Oncology (2010)

Purpose To use published literature to estimate large, medium, and small differences in quality of life (QOL) data from the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Methods An innovative method combining systematic review of published studies, expert opinions, and meta-analysis was used to estimate large, medium, and small differences for QLQ-C30 scores. Published mean data were identified from the literature. Differences (contrasts) between groups (eg, between treatment groups, age groups, and performance status groups) were reviewed by 34 experts in QOL measurement and cancer treatment. The experts, blinded to actual QOL results, were asked to predict these differences. A large difference was defined as one representing unequivocal clinical relevance. A medium difference was defined as likely to be clinically relevant but to a lesser extent. A small difference was one believed to be subtle but nevertheless clinically relevant. A trivial difference was used to describe circumstances unlikely to have any clinical relevance. Actual QOL results were combined using meta-analytic techniques to estimate differences corresponding to small, medium, or large effects. Results Nine hundred eleven articles were identified, leading to 152 relevant articles (2,217 contrasts) being reviewed by at least two experts. Resulting estimates from the meta-analysis varied depending on the subscale. Thus, the recommended minimum to detect medium differences ranges from 9 (cognitive functioning) to 19 points (role functioning). Conclusion Guidelines for the size of effects are provided for the QLQ-C30 subscales. These guidelines can be used for sample size calculations for clinical trials and can also be used to aid interpretation of differences in QLQ-C30 scores.
Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis
Authors: K.P. Tiev, T. Hua-Huy, A. Kettaneh, M. Gain, S. Duong-Quy, C. Tolédano, J. Cabane, A.T. Dinh-Xuan
Journal: European Respiratory Journal (2011)

Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc. In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion. The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng·mL −1 , with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p&lt;0.001). After a mean± sd follow-up of 33.7±10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels &gt;187 ng·mL −1 . The adjusted hazard ratio was 5.36 (95% CI 2.44–11.75; p&lt;0.001). In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.
A valid, accurate, office based non-radioactive test for gastric emptying of solids
Authors: J S Lee, M Camilleri, A R Zinsmeister, D D Burton, L J Kost, P D Klein
Journal: Gut (2000)

<h3>BACKGROUND</h3> Current breath tests for measurement of gastric emptying of solids are expensive, possibly inaccurate, and require cumbersome calculations. <h3>AIMS</h3> We wished to validate a simplified solid gastric emptying test using a [<sup>13</sup>C]<i>Spirulina platensis</i>breath test for accurate results relative to scintigraphy. <h3>SUBJECTS</h3> Thirty healthy volunteers. <h3>METHODS</h3> We measured gastric emptying of egg containing [<sup>13</sup>C]<i>S platensis</i> and<sup>99m</sup>Tc sulphur colloid by breath<sup>13</sup>CO<sub>2</sub> and scintigraphy over six hours. A generalised linear regression model was used to predict t<sub>1/2</sub> and t<sub>LAG</sub> by scintigraphy from breath<sup>13</sup>CO<sub>2</sub> data. The model was cross validated and normative data calculated for a prepacked [<sup>13</sup>C]meal. <h3>RESULTS</h3> Regression models using all breath data over six hours, for the first three hours, and for samples at 75, 90, and 180 minutes ("reduced model") predicted t<sub>1/2</sub> and t<sub>LAG</sub> values similar to scintigraphy (t<sub>LAG</sub> 43 (SD 12) min; t<sub>1/2</sub> 100 (20) min). Standard deviations of differences in t<sub>1/2</sub> and t<sub>LAG</sub> between scintigraphy and the "reduced model" were both 10 minutes. Gastric t<sub>1/2</sub> for the prepacked [<sup>13</sup>C]meal was 91 (15) min (10–90% range: 74–118). <h3>CONCLUSION</h3> The [<sup>13</sup>C]<i>S platensis</i> breath test and a simple formula using breath <sup>13</sup>CO<sub>2</sub> at baseline, 90, and 180 minutes measured gastric emptying t<sub>1/2</sub> for solids with results that were comparable with scintigraphy.
Open Randomized Trial Comparing Early Withdrawal of either Cyclosporine or Mycophenolate Mofetil in Stable Renal Transplant Recipients Initially Treated with a Triple Drug Regimen
Authors: Peter Schnuelle, Jaap Homan van der Heide, Adam Tegzess, Cornelis A. Verburgh, Leendert C. Paul, Fokko Johannes van der Woude, Johan W. de Fijter
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Cyclosporine (CsA) is the current primary immunosuppressant for the prevention of renal allograft rejection. Its chronic use is associated with various adverse effects like hypertension, hyperlipidemia, and nephrotoxicity, which in turn may contribute to chronic allograft nephropathy and cardiovascular mortality. This study compares a CsA-free maintenance regimen of mycophenolate mofetil (MMF) and corticosteroids with CsA and corticosteroids after early conversion from triple drug therapy. Eighty-four renal transplant recipients who had stable graft function on triple drug therapy with MMF, CsA, and steroids were randomly assigned to be withdrawn from either CsA (n = 44) or MMF (n = 40) at 3 mo posttransplantation. Kidney function at 1 yr was the primary endpoint. Secondary parameters of efficacy were patient and graft survival, incidence of acute rejection episodes, BP, and lipids. At study entry, the alternative treatment groups were similar with respect to demographics, renal function, dosage of CsA, BP, and concomitant medication. Both the creatinine clearance (71.7 versus 60.9 ml/min) and calculated GFR (73.2 versus 61.9 ml/min) were significantly better in MMF-treated patients at 1 yr. Conversion to MMF was associated with a decline of systolic and diastolic BP (128/76 versus 139/82 mmHg) and with a more favorable lipid profile. There was no difference in patient survival (100%) and graft survival (97.7% versus 100%). Acute rejection episodes occurred more frequently after withdrawal of CsA (11.3% versus 5.0%), but the difference was NS. Early tapering of CsA can safely be accomplished in renal transplant recipients who are stable on a triple drug regimen with MMF, thereby resulting in improved renal function, a more favorable lipid profile, and beneficial effects on posttransplant hypertension.
Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer
Authors: Timothy J. Whelan, Jean-Philippe Pignol, Mark N. Levine, Jim A. Julian, Robert MacKenzie, Sameer Parpia, Wendy Shelley, Laval Grimard, Julie Bowen, Himu Lukka, Francisco Perera, Anthony Fyles, Ken Schneider, Sunil Gulavita, Carolyn Freeman
Journal: New England Journal of Medicine (2010)

The optimal fractionation schedule for whole-breast irradiation after breast-conserving surgery is unknown.We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule. Women with invasive breast cancer who had undergone breast-conserving surgery and in whom resection margins were clear and axillary lymph nodes were negative were randomly assigned to receive whole-breast irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of 35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period of 22 days (the hypofractionated-radiation group).The risk of local recurrence at 10 years was 6.7% among the 612 women assigned to standard irradiation as compared with 6.2% among the 622 women assigned to the hypofractionated regimen (absolute difference, 0.5 percentage points; 95% confidence interval [CI], -2.5 to 3.5). At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, -6.9 to 9.8).Ten years after treatment, accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who had undergone breast-conserving surgery for invasive breast cancer with clear surgical margins and negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.)
In Vivo Thrombus Formation in Murine Models
Authors: Ulrich J.H. Sachs, Bernhard Nieswandt
Journal: Circulation Research (2007)

Platelets play a central role in hemostasis, but also in atherothrombosis, as they rapidly adhere to tissue and to one another as a response to any vascular injury. This process involves a large number of surface receptors, signaling pathways, and enzymatic cascades as well as their complex interplay. Although in vitro experiments proved successful in both identifying new receptors and pathways and developing potent and selective antithrombotic drugs, in vitro research cannot mimic the myriad hemodynamic and spatiotemporal cellular and molecular interactions that occur during the generation and propagation of thrombi in vivo. Animal models, and, with the availability of genetically modified mouse strains and of modern intravital imaging techniques, mouse models in particular, have opened new ways to identify both individual roles and the interplay of platelet proteins in complex in vivo settings. In vivo models revealed the important role of, eg, Gas6 or blood coagulation factor XII in thrombus formation, and results obtained in in vivo models raised the interesting possibility that (physiologic) hemostasis and (pathologic) thrombosis might represent 2 mechanistically different processes. This review summarizes in vivo findings that contributed significantly to our understanding of hemostatic and thrombotic processes and which may help to guide future research.
Cytomegalovirus Disease after Prophylaxis with Oral Ganciclovir in Renal Transplantation
Authors: Mark A. Schnitzler, Jeffrey A. Lowell, S. Paul Hmiel, Karen L. Hardinger, Helen Liapis, Connie S. Ceriotti, Daniel C. Brennan
Journal: Journal of the American Society of Nephrology (2003)

<h3>Background</h3> There are concerns about high levels of demand for emergency health services. The aim was to identify the characteristics of the British population with a tendency to contact emergency medical services and EDs for minor or non-urgent problems. <h3>Methods</h3> A survey of the British adult population in 2018. Six vignettes were constructed about illness in adults (cough/sore throat or diarrhoea/vomiting), injury in adults (sore rib or back pain) and fever in children (occurring weekday or weekend). <h3>Results</h3> The response rate was 42%, with 2906 respondents. 11% (319/2716) of respondents selected to contact an ambulance and 43% ED, mainly for the vignettes about fever in children and sore rib. Males, people from ethnic minority communities and older people had a tendency to contact emergency services for minor problems. Tendency to call an ambulance was also characterised by 'low resources' (manual or unskilled occupations, no car, low health literacy), worry that a symptom might be serious, distress (feeling overwhelmed by health problems) and frequent use of EDs. For EDs, there was an attraction to EDs because of availability of tests. <h3>Conclusion</h3> Whereas use of emergency ambulances for minor or non-urgent problems appeared to be driven by people's lack of resources, including lack of transport, use of EDs appeared to be driven by their attractive characteristic of offering tests quickly.
Nerve Growth Factor Is Critical for Cardiac Sensory Innervation and Rescues Neuropathy in Diabetic Hearts
Authors: Masaki Ieda, Hideaki Kanazawa, Yasuyo Ieda, Kensuke Kimura, Keisuke Matsumura, Yuichi Tomita, Takashi Yagi, Takeshi Onizuka, Kenichiro Shimoji, Satoshi Ogawa, Shinji Makino, Motoaki Sano, Keiichi Fukuda
Journal: Circulation (2006)

Background— Molecular mechanisms regulating the cardiac sensory nervous system remain poorly understood. Cardiac sensory nerve impairment causes silent myocardial ischemia, a main cause of sudden death in diabetes mellitus (DM). The present study focused on the roles of nerve growth factor (NGF) in the regulation of the cardiac sensory nervous system and analyzed the mechanism of silent myocardial ischemia in DM. Methods and Results— We screened neurotrophic factors and found that cardiac sensory nerves developed in parallel with NGF synthesized in the heart. Cardiac nociceptive sensory nerves that were immunopositive for calcitonin gene-related peptide, dorsal root ganglia (DRG), and the dorsal horn were markedly retarded in NGF-deficient mice, whereas cardiac-specific overexpression of NGF rescued these deficits. DM was induced with streptozotocin in wild-type and transgenic mice overexpressing NGF in the heart. Downregulation of NGF, calcitonin gene-related peptide–immunopositive cardiac sensory denervation, and atrophic changes in DRG were observed in DM-induced wild-type mice, whereas these deteriorations were reversed in DM-induced NGF transgenic mice. Cardiac sensory function, measured by myocardial ischemia–induced c-Fos expression in DRG, was also downregulated by DM in the wild-type mice but not in NGF transgenic mice. Direct gene transfer of NGF in the diabetic rat hearts improved impaired cardiac sensory innervation and function, determined by electrophysiological activity of cardiac afferent nerves during myocardial ischemia. Conclusions— These findings demonstrate that the development and regulation of the cardiac sensory nervous system are dependent on NGF synthesized in the heart and that DM-induced NGF reduction causes cardiac sensory neuropathy.
Molecular Mechanism for a Gateway Drug: Epigenetic Changes Initiated by Nicotine Prime Gene Expression by Cocaine
Authors: Amir Levine, YanYou Huang, Bettina Drisaldi, Edmund A. Griffin, Daniela D. Pollak, Shiqin Xu, Deqi Yin, Christine Schaffran, Denise B. Kandel, Eric R. Kandel
Journal: Science Translational Medicine (2011)

The finding that nicotine enhances the brain’s response to cocaine may explain how smoking acts as a gateway drug for this addictive stimulant.
How effective are our child health clinics?
Authors: G H C. Jenkins
Journal: BMJ (1982)

<h3>Abstract</h3> <h3>Motivation</h3> Although secondary structure predictors have been developed for decades, current ab initio methods have still some way to go to reach their theoretical limits. Moreover, the continuous effort towards harnessing ever expanding data sets and more sophisticated, deeper Ma-chine Learning techniques, has not come to an end. <h3>Results</h3> Here we present Porter 5, the latest release of one of the best performing ab initio secondary structure predictors. Version 5 achieves 84% accuracy (84% SOV) when tested on 3 classes, and 73% accuracy (77% SOV) on 8 classes, on a large independent set, significantly outper-forming all the most recent ab initio predictors we have tested. <h3>Availability</h3> The web and standalone versions of Porter5 are available at http://distilldeep.ucd.ie/porter/. <h3>Contact</h3> gianluca.pollastri@ucd.ie