tbuckley/cabot-search huggingface dataset:
Diagnosis of oesophageal spasm by ergometrine provocation.
Authors: H A Davies, M D Kaye, J Rhodes, A M Dart, A H Henderson
Journal: Gut (1982)

<h3>Abstract</h3> <h3>Background</h3> Autosomal-dominant Alzheimer’s disease (ADAD) is caused by pathogenic mutations in <i>APP, PSEN1</i>, and <i>PSEN2</i>, which usually lead to an early age at onset (&lt;65). Circular RNAs are a family of non-coding RNAs highly expressed in the nervous system and especially in synapses. We aimed to investigate differences in brain gene expression of linear and circular transcripts from the three ADAD genes in controls, sporadic AD, and ADAD. <h3>Methods</h3> We obtained and sequenced RNA from brain cortex using standard protocols. Linear counts were obtained using the TOPMed pipeline; circular counts, using python package DCC. After stringent quality control (QC), we obtained the counts for <i>PSEN1, PSEN2</i> and APP genes. Only circ<i>PSEN1</i> passed QC. We used DESeq2 to compare the counts across groups, correcting for biological and technical variables. Finally, we performed <i>in-silico</i> functional analyses using the Circular RNA interactome website and DIANA mirPath software. <h3>Results</h3> Our results show significant differences in gene counts of circ<i>PSEN1</i> in ADAD individuals, when compared to sporadic AD and controls (ADAD=22, AD=274, Controls=25 – ADADvsCO: log2FC=0.786, p=9.08×10-05, ADADvsAD: log2FC=0.576, p=2.00×10-03). The high gene counts are contributed by two circ<i>PSEN1</i> species (hsa_circ_0008521 and hsa_circ_0003848). No significant differences were observed in linear <i>PSEN1</i> gene expression between cases and controls, indicating that this finding is specific to the circular forms. In addition, the high circ<i>PSEN1</i> levels do not seem to be specific to <i>PSEN1</i> mutation carriers; the counts are also elevated in APP and <i>PSEN2</i> mutation carriers. <i>In-silico</i> functional analyses suggest that circ<i>PSEN1</i> is involved in several pathways such as axon guidance (p=3.39×10<sup>−07</sup>), hippo signaling pathway (p=7.38×10<sup>−07</sup>), lysine degradation (p=2.48×10<sup>−05</sup>) or Wnt signaling pathway (p=5.58×10<sup>−04</sup>) among other KEGG pathways. Additionally, circ<i>PSEN1</i> counts were able to discriminate ADAD from sporadic AD and controls with an AUC above 0.70. <h3>Conclusions</h3> Our findings show the differential expression of circ<i>PSEN1</i> is increased in ADAD. Given the biological function previously ascribed to circular RNAs and the results of our <i>in-silico</i> analyses, we hypothesize that this finding might be related to neuroinflammatory events that lead or that are caused by the accumulation of amyloid-beta.
Fragmented QRS as a Marker of Conduction Abnormality and a Predictor of Prognosis of Brugada Syndrome
Authors: Hiroshi Morita, Kengo F. Kusano, Daiji Miura, Satoshi Nagase, Kazufumi Nakamura, Shiho T. Morita, Tohru Ohe, Douglas P. Zipes, Jiashin Wu
Journal: Circulation (2008)

Conduction abnormalities serve as a substrate for ventricular fibrillation (VF) in patients with Brugada syndrome (BS). Signal-averaged electrograms can detect late potentials, but the significance of conduction abnormalities within the QRS complex is still unknown. The latter can present as multiple spikes within the QRS complex (fragmented QRS [f-QRS]). We hypothesized that f-QRS could indicate a substrate for VF and might predict a high risk of VF for patients with BS.In study 1, we analyzed the incidence of f-QRS in 115 patients with BS (13 resuscitated from VF, 28 with syncope, and 74 asymptomatic). f-QRS was observed in 43% of patients, more often in the VF group (incidence of f-QRS: VF 85%, syncope 50%, and asymptomatic 34%, P<0.01). SCN5A mutations occurred more often in patients with f-QRS (33%) than in patients without f-QRS (5%). In patients with syncope or VF, only 6% without f-QRS experienced VF during follow-up (43+/-25 months), but 58% of patients with f-QRS had recurrent syncope due to VF (P<0.01). In study 2, to investigate the mechanism of f-QRS, we studied in vitro models of BS in canine right ventricular tissues (n=4) and optically mapped multisite action potentials. In the experimental model of BS, ST elevation resulted from a large phase 1 notch of the action potential in the epicardium, and local epicardial activation delay reproduced f-QRS in the transmural ECG.f-QRS appears to be a marker for the substrate for spontaneous VF in BS and predicts patients at high risk of syncope.
Feasibility of altering type A behavior pattern after myocardial infarction. Recurrent Coronary Prevention Project Study: methods, baseline results and preliminary findings.
Authors: M Friedman, C E Thoresen, J J Gill, D Ulmer, L Thompson, L Powell, V Price, S R Elek, D D Rabin, W S Breall, G Piaget, T Dixon, E Bourg, R A Levy, D L Tasto
Journal: Circulation (1982)

We studied 1035 consecutive postinfarction patients to determine the feasibility of altering type A behavior and the effect such alteration might have on subsequent rates of infarction and cardiovascular death. Approximately 300 subjects were enrolled in small groups and primarily received cardiologic counseling on the usually accepted coronary risk factors. Six hundred subjects received, in addition to cardiologic counseling, advice and instructions designed to diminish the intensity of their type A behavior. The remaining subjects, serving as controls, received no counseling, but were examined and interviewed annually, as were those who dropped out of counseling groups. More than 98% of the 1035 subjects exhibited moderate-to-severe type A behavior during a videotaped structured interview. After the first year of this 5-year study, the rates of infarction and cardiovascular death were lower (p less than 0.01 and p less than 0.05, respectively) among subjects who received both cardiologic and behavioral counseling than among the control subjects. The rate of nonfatal infarction was lower (p less than 0.05) among subjects who received behavioral counseling than among those who received only cardiologic counseling or those who dropped out of either counseling group. The circumstances that most often preceded recurrent infarction or cardiovascular death were emotional crisis, excess physical activity, ingestion of a single fatty meal or a combination of these phenomena.
Liver iron concentration, stainable iron, and total body storage iron
Authors: M. Barry
Journal: Gut (1974)

Liver iron concentration has been determined chemically in 154 liver biopsies and the findings compared with the routine histological assessment of stainable parenchymal iron, performed by an independent observer. There was a significant correlation between liver iron concentration and histochemical grading but the relationship did not have a normal linear form. Absence of stainable iron corresponded to liver iron concentrations below the mean value for control male subjects (77 mug/100 mg dry liver). In general grade 1 siderosis corresponded to liver iron concentrations in the upper part of the control range and grade 2 siderosis to marginally elevated values. The transition from grade 2 to grade 3 (submaximal) siderosis represented a sharp increase in liver iron concentration and as grade 3 siderosis corresponded to a wide range of chemical values it is also the most difficult histochemical grade to interpret in quantitative terms. Grade 4 siderosis invariably indicated heavy iron excess.There was a close correlation between liver iron concentration and measurements of total body storage iron obtained by quantitative phlebotomy in patients with idiopathic haemochromatosis and by determination of DTPA-chelatable body iron in a variety of iron-loading disorders.
Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers
Authors: Sylvain Julien, Aleksandar Ivetic, Anita Grigoriadis, Ding QiZe, Brian Burford, Daisy Sproviero, Gianfranco Picco, Cheryl Gillett, Suzanne L. Papp, Lana Schaffer, Andrew Tutt, Joyce Taylor-Papadimitriou, Sarah E. Pinder, Joy M. Burchell
Journal: Cancer Research (2011)

Abstract The glycome acts as an essential interface between cells and the surrounding microenvironment. However, changes in glycosylation occur in nearly all breast cancers, which can alter this interaction. Here, we report that profiles of glycosylation vary between ER-positive and ER-negative breast cancers. We found that genes involved in the synthesis of sialyl-Lewis x (sLex; FUT3, FUT4, and ST3GAL6) are significantly increased in estrogen receptor alpha-negative (ER-negative) tumors compared with ER-positive ones. SLex expression had no influence on the survival of patients whether they had ER-negative or ER-positive tumors. However, high expression of sLex in ER-positive tumors was correlated with metastasis to the bone where sLex receptor E-selectin is constitutively expressed. The ER-positive ZR-75-1 and the ER-negative BT20 cell lines both express sLex but only ZR-75-1 cells could adhere to activated endothelial cells under dynamic flow conditions in a sLex and E-selectin–dependent manner. Moreover, L/P-selectins bound strongly to ER-negative MDA-MB-231 and BT-20 cell lines in a heparan sulfate (HS)–dependent manner that was independent of sLex expression. Expression of glycosylation genes involved in heparan biosynthesis (EXT1 and HS3ST1) was increased in ER-negative tumors. Taken together, our results suggest that the context of sLex expression is important in determining its functional significance and that selectins may promote metastasis in breast cancer through protein-associated sLex and HS glycosaminoglycans. Cancer Res; 71(24); 7683–93. ©2011 AACR.
Prognostic Value of Nodal Ratios in Node-Positive Breast Cancer
Authors: Wendy A. Woodward, Vincent Vinh-Hung, Naoto T. Ueno, Yee Chung Cheng, Melanie Royce, Patricia Tai, Georges Vlastos, Anne Marie Wallace, Gabriel N. Hortobagyi, Yago Nieto
Journal: Journal of Clinical Oncology (2006)

The American Joint Committee on Cancer staging system for breast cancer was recently updated to reflect the impact of increasing the absolute number of positive lymph nodes on prognosis. However, numerous studies suggest that nodal ratios (absolute number of involved nodes-number of nodes resected) may have greater prognostic value than absolute numbers of involved nodes. Here we examine the data supporting the use of nodal ratios in breast cancer prognosis and consider the potential advantages and disadvantages of including nodal ratios in breast cancer staging.A systematic review of the literature was conducted using the following search engines: http://www.google.com; Thomson's ISI Web of Science; PubMed.In multiple reports from both prospective and retrospectively collected data sets, nodal ratios have been shown to be significant predictors of outcome, including locoregional recurrence and overall survival. These studies span all stages of breast cancer and include various treatments as well as various statistical approaches.There is considerable data supporting the use of nodal ratios in breast cancer prognosis. A thorough and methodological evaluation of the potential prognostic importance of nodal ratios in large multicenter data sets is merited and is currently being undertaken by the International Nodal Ratio Working Group.
Influences of Spinal Anesthesia on Exercise Tolerance in Patients with Chronic Obstructive Pulmonary Disease
Authors: Philippe Gagnon, Jean S. Bussières, Fernanda Ribeiro, Serge L. Gagnon, Didier Saey, Nathalie Gagné, Steeve Provencher, François Maltais
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Lower limb muscle dysfunction contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We hypothesized that signaling from lower limb muscle group III/IV sensory afferents to the central motor command could be involved in premature cycling exercise termination in COPD.Objectives: To evaluate the effects of spinal anesthesia, which presumably inhibited central feedback from the lower limb muscle group III/IV sensory afferents on exercise tolerance and cardiorespiratory response during constant work-rate cycling exercise in patients with COPD.Methods: In a crossover and double-blind randomized design, eight patients with COPD (FEV1, 67 ± 8% predicted) completed a constant work-rate cycling exercise after sham (NaCl, interspinous L3–L4) or active (fentanyl 25 μg, intrathecal L3–L4) spinal anesthesia.Measurements and Main Results: When compared with placebo, endurance time was significantly prolonged after spinal anesthesia with fentanyl (639 ± 87 s vs. 423 ± 38 s [mean ± SEM]; P = 0.01). Ventilation and respiratory rate were reduced at isotime points under the fentanyl condition, whereas ventilatory efficiency and dead space ventilation were improved. Patients exhibited less dynamic hyperinflation at isotime points with spinal anesthesia. Consequently, the rise in dyspnea was significantly flatter during the fentanyl condition than with placebo.Conclusions: Spinal anesthesia enhanced cycling exercise tolerance in patients with COPD, mostly by reducing ventilatory response and dyspnea during exercise; these effects were possibly mediated through the inhibition of group III/IV lower limb sensory muscle afferents.Clinical trial registered with www.clinicaltrials.gov (NCT01522729).
Immunoglobulin Class Switch Recombination
Authors: W Harriman, H Volk, N Defranoux, M Wabl
Journal: Annual Review of Immunology (1993)

A B lymphocyte that produces the immunoglobulin heavy (H) chain mu may switch to the production of another heavy chain class: gamma, epsilon, or alpha. Since the new heavy chain retains the original variable (V) region, antigenic specificity is maintained. The switch is accompanied by a large deletion of DNA at the heavy chain locus. To explain how this deletion is generated, three models have been proposed: recombination between homologs, unequal sister chromatid exchange, and looping out and deletion. While none of the predicted recombination products of the first two models have been found, both by-products of looping out--inversions and circular DNA--have been isolated. Thus looping out and deletion appears to be the appropriate model to explain the genetic events leading to the immunoglobulin heavy chain class switch. One requirement for switching may be transcription of the constant (C) region to which the cell switches. The switch rearrangement is catalyzed by a switch recombinase, and the isolation of the components of this putative enzyme system is in progress. Although the switch deletion is an accepted fact, the discussion is enlivened by scenarios for switching without DNA rearrangement; such suggestions include processing at the RNA level and trans-splicing.
A Method for Culturing Beta Hemolytic Streptococci from the Throat
Authors: LEWIS W. WANNAMAKER
Journal: Circulation (1965)

EXCEPT in the case of scarlet fever, no completely satisfactory clinical criteria are available for distinguishing patients with streptococcal respiratory infections from those with respiratory illnesses due to other agents.Many instances of pharyngitis and tonsillitis- with or without exudate-are nonbacterial in etiology; some have been linked with the new group of adenoviruses.These nonstreptococ- cal infections do not lead to rheumatic fever, and patients with such infections are not benefited by antibiotic therapy.Because the diagnosis of a streptococcal in- fection of the upper respiratory tract on clini- cal groun,ds is necessarily presumptive, a culture of the throat provides valuable labora- tory confirmation or rejection of the clinical impression.Throat cultures from patients with acute streptococcal infections are posi- tive for beta hemolytic streptococci in over 95 per cent of cases.A throat culture is a relatively simple lab- oratory procedure to perform, and a preliminary report is available within 18 hours.In certain doubtful cases, it is possible for the physician to use his judgment in withholding antibiotic therapy until the results of the throat culture are available.A throat culture is also a useful guide for determining whether From the American Heart Association, New York, New York.
Comparing different flow rates (20 and 35 l/min) under high-nasal flow therapy for the obstructive sleep apnoea syndrome (OSAS)
Authors: Georg Nilius, Ulrike Domanskie, Karl-Josef Franke, Karl-Heinz Ruhle, Hartmut Schneider
Journal: European Respiratory Journal (2011)

Introduction: We have demonstrated that 20 l/min nasal insufflation of airflow (HNF) can treat a subgroup of OSAS patients (Nilius G et al. Chest. 2010; 137:521-8). The aim of this study was to compare the effect of two flow rates (20 l/min (HNF20) and 35 l/min (HNF35)) on sleep disordered breathing.

Methods: 18 CPAP-naive patients (6 women, age 56.6±7.3, BMI 32.6±3.8 kg/m2, ESS 9.3±5.2) with more than 50% Hypopnoeas during a diagnostic night were recruited. During the treatment night both HNF20 and HNF35 were administered in a random order for a minimum of three hours each.

Results: The total event rate (AHI) in NREM/REM sleep was at baseline 25±13/37±23, at HF20 L/min 23±14/22±22 and at HF35 L/min 19,0±13/15±18 (P<0.05 for REM). There were significant improvement HI, but AI at 35 L/min versus 20 L/min in NREM and REM sleep. The lack of AI responses was associated with a significant increase in cenctral AI (baseline vs HNF20 vs HNF35; 1 vs 8 vs 6 events/hour). Nevertheless Oxygenation (T90) improved considerably with HNF35 compared to HNF20 and baseline in both sleep states.

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Conclusion: A flow rate of 35 LPM of nasal insufflation is more effective in lowing obstructive hypopneas and improving oxygenation than 20 LPM. Nasal insufflation, however, can increase the event rate of central apneas, independently of the flow rate, which might offset therapeutic responses in some patients.
Tumoral calcinosis in Britain.
Authors: K S Vasudev, E Tapp, M Harris, R C Jennings
Journal: BMJ (1973)

Contact Sensitivity to Toothpaste Snt,-I wish to report three cases of acute contact sensitivity to a new toothpaste (Close-Up).Each of these patients changed from their regular toothpaste after receiving a free sample of Close-Up through the post.Case 1.-A 30-year-old woman gave a two- month history of a sore mouth with swelling and cracking of the lips.Two weeks before this developed she changed her toothpaste to Close-Up and used it once or twice a day.She showed fissuring of the lips with desquamation and oedema of the surrounding skin.Case 2.-A 36-year-old man developed a weeping eruption at the right side of the mouth with sore gums.He had used Close-Up once a day for three months.There was a right-sided angular cheilitis with swollen gums and desquamation of the tip of the tongue.Case 3.-A 22-year-old woman used Close-Up three times a day for a week.On the sixth day she developed painful ulcers on the inside of her mouth, particularly inside the lower lip.In each case signs and symptoms settled within one week of stopping the use of the new toothpaste.
A Phase I Pharmacokinetic and Biological Correlative Study of Oblimersen Sodium (Genasense, G3139), an Antisense Oligonucleotide to the Bcl-2 mRNA, and of Docetaxel in Patients with Hormone-Refractory Prostate Cancer
Authors: Anthony W. Tolcher, John Kuhn, Garry Schwartz, Amita Patnaik, Lisa A. Hammond, Ian Thompson, Howard Fingert, David Bushnell, Shazli Malik, Jeffrey Kreisberg, Elzbieta Izbicka, Leslie Smetzer, Eric K. Rowinsky
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To assess the feasibility of administering oblimersen sodium, a phosphorothioate antisense oligonucleotide directed to the Bcl-2 mRNA, with docetaxel to patients with hormone-refractory prostate cancer; to characterize the pertinent pharmacokinetic parameters, Bcl-2 protein inhibition in peripheral blood mononuclear cell(s) (PBMC) and tumor; and to seek preliminary evidence of antitumor activity. Experimental Design: Patients were treated with increasing doses of oblimersen sodium administered by continuous i.v. infusion on days 1 to 6 and docetaxel administered i.v. over 1 h on day 6 every 3 weeks. Plasma was sampled to characterize the pharmacokinetic parameters of both oblimersen and docetaxel, and Bcl-2 protein expression was measured from paired collections of PBMCs pretreatment and post-treatment. Results: Twenty patients received 124 courses of the oblimersen and docetaxel combination at doses ranging from 5 to 7 mg/kg/day oblimersen and 60 to 100 mg/m2 docetaxel. The rate of severe fatigue accompanied by severe neutropenia was unacceptably high at doses exceeding 7 mg/kg/day oblimersen and 75 mg/m2 docetaxel. Nausea, vomiting, and fever were common, but rarely severe. Oblimersen mean steady-state concentrations were 3.44 ± 1.31 and 5.32 ± 2.34 at the 5- and 7-mg/kg dose levels, respectively. Prostate-specific antigen responses were observed in 7 of 12 taxane-naïve patients, but in taxane-refractory patients no responses were observed. Preliminary evaluation of Bcl-2 expression in diagnostic tumor specimens was not predictive of response to this therapy. Conclusions: The recommended Phase II doses for oblimersen and docetaxel on this schedule are 7 mg/kg/day continuous i.v. infusion days 1 to 6, and 75 mg/m2 i.v. day 6, respectively, once every 3 weeks. The absence of severe toxicities at this recommended dose, evidence of Bcl-2 protein inhibition in PBMC and tumor tissue, and encouraging antitumor activity in HPRC patients warrant further clinical evaluation of this combination.
Assessment of mineral fibres from human lung tissue.
Authors: J M Davis, B Gylseth, A Morgan
Journal: Thorax (1986)

Since the discovery that the inhalation of asbestos fibres could cause pulmonary disease attempts have been made to relate the level of lung damage found at necropsy to the lung fibre burden. At first, studies of asbestos fibres and bodies from lung tissue were qualitative' 2; later the first attempts at quantification used estimations of fibre mass.3 For many years studies of lung fibre burden have been based on the counting of fibres by increasingly sophisticated techniques but the published results have not been-directly comparable in many cases, and from the few interlaboratory comparisons that have been undertaken it has become obvious that large variations in counts may be produced from the same lung. At present counts of asbestos fibres from lung tissue are becoming very important in medicolegal cases all over the world, often without appreciation of their limitations. For this reason an international workshop was held in Oxford, from 17 to 19 September 1984, to discuss all technical problems related to the estimation of the content of mineral fibres in lung tissue and to determine what could be done to make results from different laboratories more directly comparable. This paper summarises the main points of discussion and the conclusions reached. A list of workshop participants is given at the end.
Complete Resolution of Life-Threatening Bleomycin-Induced Pneumonitis After Treatment With Imatinib Mesylate in a Patient With Hodgkin's Lymphoma: Hope for Severe Chemotherapy-Induced Toxicity?
Authors: Fabrizio Carnevale-Schianca, Susanna Gallo, Delia Rota-Scalabrini, Dario Sangiolo, Marco Fizzotti, Daniela Caravelli, Antonio Capaldi, Giancarlo Anselmetti, Erica Palesandro, Lorenzo D'Ambrosio, Valentina Coha, Remo Obert, Massimo Aglietta, Giovanni Grignani
Journal: Journal of Clinical Oncology (2011)