tbuckley/cabot-search huggingface dataset:
Repeated Episodes of Hypoglycemia as a Potential Aggravating Factor for Preclinical Atherosclerosis in Subjects With Type 1 Diabetes
Authors: Marga Giménez, Rosa Gilabert, Joan Monteagudo, Anna Alonso, Roser Casamitjana, Carles Paré, Ignacio Conget
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate through early preclinical atherosclerosis assessment whether repeated episodes of hypoglycemia represent an aggravating factor for macrovascular disease in type 1 diabetes. RESEARCH DESIGN AND METHODS After sample-size calculation, a case-control study of 25 patients with type 1 diabetes and repeated severe/nonsevere hypoglycemia (H-group) compared with 20 age- and sex-matched type 1 diabetes control subjects (C-group) was designed. Assessment of preclinical atherosclerosis consisted of flow-mediated brachial dilatation (FMD) and carotid and femoral intima-media thickness (IMT) studies. To consider hypoglycemia awareness, two different questionnaires and symptomatic response to an acute induction to hypoglycemia were used. Evaluation of the glycemic profile was obtained from continuous glucose monitoring. Endothelial function/inflammation markers were measured in euglycemia/hypoglycemia. A multivariate linear regression analysis was performed to test whether repeated hypoglycemia was independently associated with atherosclerosis. RESULTS H-group subjects displayed hypoglycemia unawareness and presented a higher percentage of continuous glucose values and area under the curve &amp;lt;70 mg/dl compared with the C-group (14.2 ± 8.9 vs. 6.3 ± 7.1%, P &amp;lt; 0.02 and 2.4 ± 1.8 vs. 0.6 ± 1.0 mg/dl/day, P &amp;lt; 0.01). The percentage of maximal FMD was lower in the H-group than in the C-group (6.52 ± 2.92 vs. 8.62 ± 3.13%, P &amp;lt; 0.05). A significantly higher IMT was observed at both carotid and femoral sites in the H-group (carotid 0.53 ± 0.09 vs. 0.47 ± 0.08 mm, P &amp;lt; 0.05 and femoral 0.51 ± 0.17 vs. 0.39 ± 0.09 mm, P &amp;lt; 0.05). Baseline inflammation and endothelial function markers were higher in the H-group (leukocytes 7.0 ± 1.8 vs. 5.6 ± 1.4 × 103/ml, von Willebrand factor 119 ± 29 vs. 93 ± 26%, fibrinogen 2.82 ± 0.64 vs. 2.29 ± 0.44g/l, and soluble intercellular adhesion molecule-1 408 ± 224 vs. 296 ± 95 ng/ml; P &amp;lt; 0.05 for all). CONCLUSIONS In addition to the induction of hypoglycemia unawareness and an increased risk for severe hypoglycemia, repeated hypoglycemia could be related to and considered an aggravating factor for preclinical atherosclerosis in type 1 diabetes. The precise mechanisms explaining this association remain to be clarified.
Exogean: a framework for annotating protein-coding genes in eukaryotic genomic DNA.
Authors: Sarah Djebali, Franck Delaplace, Hugues Roest Crollius
Journal: Genome biology (2006)

Abstract Background Accurate and automatic gene identification in eukaryotic genomic DNA is more than ever of crucial importance to efficiently exploit the large volume of assembled genome sequences available to the community. Automatic methods have always been considered less reliable than human expertise. This is illustrated in the EGASP project, where reference annotations against which all automatic methods are measured are generated by human annotators and experimentally verified. We hypothesized that replicating the accuracy of human annotators in an automatic method could be achieved by formalizing the rules and decisions that they use, in a mathematical formalism. Results We have developed Exogean, a flexible framework based on directed acyclic colored multigraphs (DACMs) that can represent biological objects (for example, mRNA, ESTs, protein alignments, exons) and relationships between them. Graphs are analyzed to process the information according to rules that replicate those used by human annotators. Simple individual starting objects given as input to Exogean are thus combined and synthesized into complex objects such as protein coding transcripts. Conclusion We show here, in the context of the EGASP project, that Exogean is currently the method that best reproduces protein coding gene annotations from human experts, in terms of identifying at least one exact coding sequence per gene. We discuss current limitations of the method and several avenues for improvement.
Increased sensitivity of T lymphocytes to tumor necrosis factor receptor 1 (TNFR1)– and TNFR2-mediated apoptosis in HIV infection: relation to expression of Bcl-2 and active caspase-8 and caspase-3
Authors: Luzia Maria de Oliveira Pinto, Sylvie Garcia, Hervé Lecoeur, Christophe Rapp, Marie-Lise Gougeon
Journal: Blood (2002)
Exacerbation of chronic active Epstein-Barr virus infection in a patient with rheumatoid arthritis receiving humanised anti-interleukin-6 receptor monoclonal antibody
Authors: J Ogawa, M Harigai, T Akashi, K Nagasaka, F Suzuki, S Tominaga, N Miyasaka
Journal: Annals of the Rheumatic Diseases (2006)

We describe deterioration of chronic active Epstein–Barr virus (CAEBV) infection in a patient with rheumatoid arthritis who received a single infusion of humanised anti-IL6 receptor monoclonal antibody (tocilizumab). A 60-year-old woman with rheumatoid arthritis who had been treated with methotrexate developed lymphadenopathy in October 1999, which was ameliorated in 2 months by cessation of methotrexate. Re-institution of methotrexate in September 2000 led to recurrence of lymphadenopathy, which was diagnosed as necrotising lymphadenitis by histological examination, with high titres of anti-Epstein–Barr virus (EBV) antibodies (antiviral capsid antigens IgG 1:1280, anti-early antigens IgG 1:640) and EBV DNA in plasma (3100 copies/ml). The lymphadenopathy gradually disappeared after cessation of methotrexate at the expense of active arthritis. In July 2001, the patient was …
Total Respiratory Inertance and Its Gas and Tissue Components in Normal and Obese Men *
Authors: J. T. Sharp, J. P. Henry, S. K. Sweany, W. R. Meadows, R. J. Pietras
Journal: Journal of Clinical Investigation (1964)

Total respiratory inertance may be defined as that component of the total impedance to breathing that relates to acceleration of respiratory gas and of all tissue elements (lungs, rib cage, diaphragm, and abdominal contents) that move during respiration. It is expressed in units of pressure required to overcome this inertial component of the total impedance and produce air flow acceleration of 1 L per second per second. Thus its units are centimeters H2O per liter per second2. Intuitively, one would suspect that the inertance of the chest and the abdomen should be increased in severely obese subjects. In investigations of total respiratory mechanics in excessively obese persons, we made measurements of total respiratory inertance. In addition, we attempted to separate the total respiratory inertance into its gas and tissue (including lung tissue, chest wall, and abdominal) components in three normal and three excessively obese subjects. These data form the substance of this report. Inertance data on the normal human respiratory system were first published by DuBois, Brody, Lewis, and Burgess (1) in 1956. These authors, assuming that the respiratory system behaves mechanically as a simple or lumped physical system, determined the total compliance and the natural frequency of the respiratory system. They then calculated the total inertance of the respiratory system by using the simple physical relationship by which the natural frequency of a system may be predicted if its elastic and inertial characteristics are known: fn = 1/274 1/jI *C, where fn
A Phase II Trial of Gefitinib (Iressa, ZD1839) in Stage IV and Recurrent Renal Cell Carcinoma
Authors: Nancy A. Dawson, Chuanfo Guo, Richard Zak, Brenda Dorsey, Jeanne Smoot, Jade Wong, Arif Hussain
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in 75 to 90% of renal cell carcinomas and may play a role in tumor initiation and progression. Gefitinib (Iressa, ZD1839) is a potent, selective EGFR-tyrosine kinase inhibitor. This trial was undertaken to assess the efficacy and toxicity of gefitinib in advanced renal cell carcinoma. Experimental Design: Oral gefitinib, 500 mg once daily, was given continuously. A single-dose reduction to 250 mg daily was allowed for toxicity. The primary end point was response rate (defined as complete remission + partial remission + stable disease). Secondary end points were progression-free survival, overall survival, toxicity, and correlation of response with EGFR status. Results: Twenty-one patients were enrolled on this study, and all are evaluable for response and toxicity. Patient characteristics were median age 61 (range, 35–78 years); 17 males, 4 females; median performance status 0 (range 0–2); median number of prior systemic therapies 1 (range, 0–3). The median and mean number of cycles of therapy received was 3 and 4.7 (range, 1–14+). The best response was stable disease in eight patients (38%). Median progression-free survival was 2.7 months. Median overall survival was 8.3 months. The difference in overall survival was significantly different between patients with progressive disease versus stable disease (6.1 months versus 16+ months; Log-Rank test P value &amp;lt; 0.0001). Three patients required a dose reduction, all for grade 3 diarrhea. There was no apparent correlation between EGFR status and stability of disease or progression of disease. Conclusions: Gefitinib is without significant conventional activity in renal cell carcinoma. The relation of “stable disease” to treatment or to disease-related prognostic heterogeneity remains to be defined.
Surgical management of morbid obesity.
Authors: S N Joffe
Journal: Gut (1981)

Progress reportSurgical management of morbid obesity Morbid obesity describes a condition of more than twice the 'ideal weight' for at least five years despite attempts at an effective and sustained weight reduction."qThe surgical approach to morbid obesity lies in the dual premise that the condition is serious and of life-shortening severity and that long-term medical treatment by prolonged starvation,5-8 hypnotherapy,9 psycho- therapy,10 anorexic and anti-obesity drugs11-13 usually fails.1-314-16Jejunoileal bypass Kremen's experimental17 and Payne's clinical studiesl 18 have led to more than 400 publications on the subject reporting over 10 000 patients.Most articles appeared during the last six years and 50 % deal with only 5 %. of the patients.Approximately half the patients have had a Payne procedure,1 one- third a Scott,19 and the remaining operations are modifications of these two procedures or are not stated.20Theoretical advantages are given for each procedure regarding weight loss and decrease in related morbidity.3 14 16 [21][][23][24][25][26][27][28][29][30] The aim is to leave approximately 10% of the small bowel in continuity for absorptionl-3163' and Maclean's review32 concludes that both types are successful if the length of functioning bowel is between 45 and 75 cm. OPERATIONIn Payne and De Wind's operation, 35 cm of jejunum is anastomosed end- to-side to 10 cm of ileum.'33With Scott's end-to-end operation, 30 cm of jejunum is anastomosed to either 30, 20, or 15 cm of ileum219 3 5 and the 90% bypassed small bowel is drained into the colon.23Modifications include anastomosis of gallbladder to the proximal excluded loop to reduce diarrhoea,36-38 automatic stapling,39 plication of the ileum,40 or formation of a valve.4'The overall mortality in 2500 patients was 3.1 %. with a range from 0 to 11.5 %.2 16 21 29 31-4 Immediate postoperative complications can be as high as 30% with wound problems being the commonest.'43245Death is due to thromboembolism, myocardial infarction, and sepsis.14 16 22 24 33 34 46WEIGHT LOSS Weight loss cannot be predicted3 and comparisons between reports are difficult because of variations in operative technique and follow-up assess- ment.'6Quaade20 found only 45 publications (171 1 patients) relating to weight loss at one year and only five reports referring to more than a five year follow-up.Data from six well-documented series indicate a 20% weight loss within six months, and about 33 % by the first year.47Weight loss is due to both malabsorption and decreased dietary intake.48 49The only prospective randomised study comparing J-I bypass and medical treatment has been conducted by the Danish Obesity Project in 130 patients.20 30 50At 24 months,
Pulmonary vascular resistance and compliance relationship in pulmonary hypertension
Authors: Denis Chemla, Edmund M.T. Lau, Yves Papelier, Pierre Attal, Philippe Hervé
Journal: European Respiratory Journal (2015)

Right ventricular adaptation to the increased pulmonary arterial load is a key determinant of outcomes in pulmonary hypertension (PH). Pulmonary vascular resistance (PVR) and total arterial compliance (C) quantify resistive and elastic properties of pulmonary arteries that modulate the steady and pulsatile components of pulmonary arterial load, respectively. PVR is commonly calculated as transpulmonary pressure gradient over pulmonary flow and total arterial compliance as stroke volume over pulmonary arterial pulse pressure (SV/PApp). Assuming that there is an inverse, hyperbolic relationship between PVR and C, recent studies have popularised the concept that their product (RC-time of the pulmonary circulation, in seconds) is "constant" in health and diseases. However, emerging evidence suggests that this concept should be challenged, with shortened RC-times documented in post-capillary PH and normotensive subjects. Furthermore, reported RC-times in the literature have consistently demonstrated significant scatter around the mean. In precapillary PH, the true PVR can be overestimated if one uses the standard PVR equation because the zero-flow pressure may be significantly higher than pulmonary arterial wedge pressure. Furthermore, SV/PApp may also overestimate true C. Further studies are needed to clarify some of the inconsistencies of pulmonary RC-time, as this has major implications for our understanding of the arterial load in diseases of the pulmonary circulation.
Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell–mediated liver regeneration
Authors: Peter Jelnes, Eric Santoni-Rugiu, Morten Rasmussen, Susanne Lune Friis, Jens Hiriis Nielsen, Niels Tygstrup, Hanne Cathrine Bisgaard
Journal: Hepatology (2007)

The experimental protocols used in the investigation of stem cell–mediated liver regeneration in rodents are characterized by activation of the hepatic stem cell compartment in the canals of Hering followed by transit amplification of oval cells and their subsequent differentiation along hepatic lineages. Although the protocols are numerous and often used interchangeably across species, a thorough comparative phenotypic analysis of oval cells in rats and mice using well-established and generally acknowledged molecular markers has not been provided. In the present study, we evaluated and compared the molecular phenotypes of oval cells in several of the most commonly used protocols of stem cell–mediated liver regeneration—namely, treatment with 2-acetylaminofluorene and partial (70%) hepatectomy (AAF/PHx); a choline-deficient, ethionine-supplemented (CDE) diet; a 3,5-diethoxycarbonyl-1,4-dihydro-collidin (DDC) diet; and N -acetyl-paraaminophen (APAP). Reproducibly, oval cells showing reactivity for cytokeratins (CKs), muscle pyruvate kinase (MPK), the adenosine triphosphate–binding cassette transporter ABCG2/BCRP1 (ABCG2), alpha-fetoprotein (AFP), and delta-like protein 1/preadipocyte factor 1 (Dlk/Pref-1) were induced in rat liver treated according to the AAF/PHx and CDE but not the DDC protocol. In mouse liver, the CDE, DDC, and APAP protocols all induced CKs and ABCG2-positive oval cells. However, AFP and Dlk/Pref-1 expression was rarely detected in oval cells. Conclusion: Our results delineate remarkable phenotypic discrepancies exhibited by oval cells in stem cell–mediated liver regeneration between rats and mice and underline the importance of careful extrapolation between individual species. (Hepatology 2007;45:1462–1470.)
Comparison of the polysomnographic apnoea-hypopnea-index with the oxygen desaturation index in patients with obstructive sleep apnoea
Authors: Zayd Tippu, Martino Pengo, Chris Kosky, Joerg Steier
Journal: European Respiratory Journal (2014)

Background  Polysomnography (NPSG) is the gold standard to diagnose obstructive sleep apnoea (OSA) but nocturnal pulse oximetry could be an easy alternative. We investigated the correlation between the oxygen desaturation index (ODI>3%) and the NPSG derived apnoea-hypopnoea-index (AHI) to determine the accuracy of nocturnal pulse oximetry.   PatientsM p vs  0.914 (p=0.17) in obese patients.   Conclusion  ODI>3% as measured by nocturnal pulse oximetry, compared to AHI, is within the range of the 5% acceptable error margin. A wider use of nocturnal pulse oximetry as a cost-effective case finding tool for OSA in the general population can help to facilitate access to sleep services and accelerate time to treatment.
Cytokine and murine coxsackievirus B3 myocarditis. Interleukin-2 suppressed myocarditis in the acute stage but enhanced the condition in the subsequent stage.
Authors: C Kishimoto, Y Kuroki, Y Hiraoka, H Ochiai, M Kurokawa, S Sasayama
Journal: Circulation (1994)

BACKGROUND It has been shown that the development of coxsackievirus B3 (CB3) myocarditis is regulated by T cells and not by B cells. Interleukin-2 (IL-2) is a T-cell-derived cytokine that stimulates the growth of T cells. This study was carried out to determine the effects of IL-2 on CB3-infected BALB/c mice. METHODS AND RESULTS In two separate experiments, recombinant human IL-2 (5 x 10(4) U) was administered subcutaneously to 30 mice early (days 0 to 7) and 30 mice late (days 7 to 14) after infection with CB3. Each experiment had a control group of infected animals that did not receive IL-2. On days 7 and 10, splenic natural killer (NK) cell activity determined by 51Cr release assay and the distribution of myocardial lymphocyte subsets were compared in the treated and untreated groups. In the early treatment experiment, survival at 7 days was higher in treated compared with control animals, myocardial virus titers were lower, inflammatory cell infiltration was less (as was the severity of necrosis at the time the mice were killed), and NK cell activity was higher. However, in the late treatment experiment, survival at 14 days was lower in treated compared with control animals, and there was more infiltration, more severe necrosis, and more T-cell infiltration, but the NK cell activity did not differ significantly. In a third experiment similar to the late experiment described above but involving infected athymic nude mice, we confirmed the lack of effect of late in vivo administration of IL-2 on outcome. CONCLUSIONS IL-2 has the capacity to limit CB3 myocarditis by enhancing NK cell activity in the acute viremic stage, resulting in a reduction of cardiac pathology. However, in the subacute aviremic stage, in contrast, IL-2 exacerbates the course and severity of the disease by increasing the number of T cells infiltrating the myocardium. That is, IL-2 has differential effects on acute CB3 myocarditis. IL-2 is beneficial if treatment is given early but later in murine CB3 myocarditis.
A conserved human germline V kappa gene directly encodes rheumatoid factor light chains.
Authors: V Radoux, P P Chen, J A Sorge, D A Carson
Journal: The Journal of Experimental Medicine (1986)

The full-length gene that encodes the light chain variable regions of an idiotypically related group of human IgM kappa rheumatoid factors (RFs) has been cloned and sequenced. The deduced amino acid sequence is identical to four separate RF proteins. These results prove that genes capable of encoding human anti-IgG autoantibody light chains without any somatic mutation are present in the kappa gene repertoire of normal people.
Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans.
Authors: V K Somers, A L Mark, F M Abboud
Journal: Journal of Clinical Investigation (1991)

Animal studies have demonstrated that activation of the baroreflex by increases in arterial pressure inhibits cardiovascular and ventilatory responses to activation of peripheral chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex activation on the sympathetic response to stimulation of PC and central chemoreceptors in humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor stimulus were also obtained as an internal reflex control to determine the selectivity of the interactive influence of baroreflex activation. Baroreflex activation was achieved by raising mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine (PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve (microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107 U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 U/min during hypercapnia and PE (P less than 0.05). Like hypercapnia (but unlike hypoxia) the cold pressor test also increased SNA during PE. We conclude that baroreflex activation selectively abolishes the SNA response to hypoxia but not to hypercapnia or the cold pressor test. The inhibitory interaction of the baroreflex and the peripheral chemoreflex may be explained by convergence of baroreceptor and peripheral chemoreceptor afferents on neurons in the medulla.
Orientational Perception: IV. Time and Length Perception in Depersonalized and Derealized Patients and Controls Under Positive Feedback Conditions
Authors: DANIEL CAPPON, ROBIN BANKS
Journal: American Journal of Psychiatry (1969)

Fifteen derealized patients reporting distortions in time and/or space perception and 15 matched controls were tested for differences in their perception of time and space. When the test responses were "fed back" as the input on subsequent trials in order to amplify small but consistent errors, no differences were found. The authors conclude that at this level of illness (depersonalization and derealization), and despite their reports, psychiatric patients do not make a significant number of errors in time and space perception.