tbuckley/cabot-search huggingface dataset:
Temperature of central versus peripheral fractions of exhaled air in subjects without and with airway diseases
Authors: Todor Popov, Tanya Kralimarkova, Dimitar Popov, Andrey Popov, Jaswinder Gill, Vasil Dimitrov
Journal: European Respiratory Journal (2013)

Background.  Measurement of exhaled breath temperature (EBT) has been suggested as a method to detect and monitor airways pathology. Sampling of portions of exhaled air at different time points of deep uniform exhalations could allow assessment of the relative contribution of central (Caw) versus peripheral airways (Paw) to the overall thermal balance, which could be used to characterize different disease states.   Methods.  We developed a fast reacting mini inflatable balloon valve system operated by a computer based pneumatic controller to allow sampling of different portions of exhaled air. The system has the size of a standard mouthpiece and is mounted on a hand-held device for EBT measurement (X-halo, Delmedica Investments, Singapore). It is individually calibrated and allows sampling air of Caw (the initial third of the exhaled air volume) and of Paw (the last third of the air volume). Switching between the two measurement modes is made by specially designed software. Measurements were made in subjects without respiratory disease (N), in patients with controlled (A-C) and exacerbated asthma (A-E), and in COPD (C) patients.   Results.  EBT increased by 0.20oC (range 0.15 – 0.25) from Caw to Paw in N; in A-C this increase was 0.45oC (0.30-0.50); in A-E the increase reached up to 1.10 oC; in a severe C patient EBT dropped by 0.20oC. In one N subject and in one A-C patient the Caw-Paw difference increased by 0.60oC and 1.05oC respectively in the course of a common cold.   Conclusion.  Measuring differences between central and peripheral EBT allows capturing a clear signal that could help characterize different airway disease phenotypes and monitor their control.
The Value of Routine Serum Carcino-Embryonic Antigen Measurement and Computed Tomography in the Surveillance of Patients After Adjuvant Chemotherapy for Colorectal Cancer
Authors: Ian Chau, Mark J. Allen, David Cunningham, Andrew R. Norman, Gina Brown, Hugo E.R. Ford, Niall Tebbutt, Diana Tait, Mark Hill, Paul J. Ross, Jacqui Oates
Journal: Journal of Clinical Oncology (2004)

This analysis aims to evaluate routine carcino-embryonic antigen (CEA) and computed tomography (CT) of thorax, abdomen, and pelvis as part of protocol-specified follow-up policy for colorectal cancer (CRC).Patients with resected stage II and III CRC were randomly assigned to bolus fluorouracil/leucovorin or protracted venous infusion fluorouracil. Following completion of chemotherapy, patients were seen in clinic at regular intervals for 5 years. CEA was measured at each clinic visit, and CT of thorax, abdomen, and pelvis was performed at 12 and 24 months after commencement of chemotherapy.Between 1993 and 1999, 530 patients were recruited. The median follow-up was 5.6 years. Disease relapses were observed in 154 patients. Relapses were detected by symptoms (n = 65), CEA (n = 45), CT (n = 49), and others (n = 9). Fourteen patients, whose relapses were detected by CT, had a concomitant elevation of CEA and were included in both groups. The CT-detected group had a better survival compared with the symptomatic group from the time of relapse (P =.0046). Thirty-three patients (21%) proceeded to potentially curative surgery for relapse and enjoyed a better survival than those who did not (P <.00001). For patients who underwent hepatic or pulmonary metastatic resection, 13 (26.5%) were in the CT group, eight (17.8%) in the CEA group, and only two (3.1%) in the symptomatic group (CT v symptomatic, P <.001; CEA v symptomatic, P =.015).Surveillance CT and CEA are valuable components of postoperative follow-up in stage II and III colorectal cancer.
Identification of a gene signature of a pre-transformation process by senescence evasion in normal human epidermal keratinocytes
Authors: Nathalie Martin, Clara Salazar-Cardozo, Chantal Vercamer, Louise Ott, Guillemette Marot, Predrag Slijepcevic, Corinne Abbadie, Olivier Pluquet
Journal: Molecular Cancer (2014)

Epidemiological data show that the incidence of carcinomas in humans is highly dependent on age. However, the initial steps of the age-related molecular oncogenic processes by which the switch towards the neoplastic state occurs remain poorly understood, mostly due to the absence of powerful models. In a previous study, we showed that normal human epidermal keratinocytes (NHEKs) spontaneously and systematically escape from senescence to give rise to pre-neoplastic emerging cells. Here, this model was used to analyze the gene expression profile associated with the early steps of age-related cell transformation. We compared the gene expression profiles of growing or senescent NHEKs to post-senescent emerging cells. Data analyses were performed by using the linear modeling features of the limma package, resulting in a two-sided t test or F-test based on moderated statistics. The p-values were adjusted for multiple testing by controlling the false discovery rate according to Benjamini Hochberg method. The common gene set resulting of differential gene expression profiles from these two comparisons revealed a post-senescence neoplastic emergence (PSNE) gene signature of 286 genes. About half of these genes were already reported as involved in cancer or premalignant skin diseases. However, bioinformatics analyses did not highlight inside this signature canonical cancer pathways but metabolic pathways, including in first line the metabolism of xenobiotics by cytochrome P450. In order to validate the relevance of this signature as a signature of pretransformation by senescence evasion, we invalidated two components of the metabolism of xenobiotics by cytochrome P450, AKR1C2 and AKR1C3. When performed at the beginning of the senescence plateau, this invalidation did not alter the senescent state itself but significantly decreased the frequency of PSNE. Conversely, overexpression of AKR1C2 but not AKR1C3 increased the frequency of PSNE. To our knowledge, this study is the first to identify reprogrammation of metabolic pathways in normal keratinocytes as a potential determinant of the switch from senescence to pre-transformation.
Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation.
Authors: M H Tao, R I Smith, S L Morrison
Journal: The Journal of Experimental Medicine (1993)

Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320-Lys322 has been identified as a key binding motif for the first component of complement, C1q, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specific residues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in gamma 4 is critical for determining the inability of that isotype to bind C1q and activate complement. Additionally, we provide further evidence that levels of C1q binding do not necessarily correlate with levels of complement activity, and that C1q binding alone is not sufficient for complement activation.
Comparison of the utility of multiple breath inert gas washout parameters in cystic fibrosis
Authors: P. D. Robinson, A. Lindblad, P. M. Gustafsson
Journal: Thorax (2010)

Ventilation inhomogeneity, measured using multiple breath washout (MBW), reflects small airway function and has emerged as a valuable tool in cystic fibrosis (CF). Improved sensitivity to detect early lung damage has been suggested from preschool children through to adults and confirmed in high-resolution CT (HRCT) studies.1 Longitudinal utility is now emerging.2 A large number of parameters reflecting overall ventilation inhomogeneity have been proposed, but consensus is lacking about the optimal parameter to report.

The two …
Effect of Computer-Generated Tailored Feedback on Glycemic Control in People With Diabetes in the Community
Authors: Diana Sherifali, Janet L. Greb, Gaya Amirthavasar, Dereck Hunt, R. Brian Haynes, William Harper, Anne Holbrook, Sarah Capes, Ron Goeree, Daria O’Reilly, Eleanor Pullenayegum, Hertzel C. Gerstein
Journal: Diabetes Care (2011)

It is unknown whether computer-generated, patient-tailored feedback leads to improvements in glycemic control in people with type 2 diabetes.We recruited people with type 2 diabetes aged ≥ 40 years with a glycated hemoglobin (A1C) ≥ 7%, living in Hamilton, Canada, who were enrolled in a community-based program (Diabetes Hamilton) that provided regular evidence-based information and listings of community resources designed to facilitate diabetes self-management. After completing a questionnaire, participants were randomly allocated to either receive or not receive periodic computer-generated, evidence-based feedback on the basis of their questionnaire responses and designed to facilitate improved glycemic control and diabetes self-management. The primary outcome was a change in A1C after 1 year.A total of 465 participants (50% women, mean age 62 years, and mean A1C 7.83%) were randomly assigned, and 12-month A1C values were available in 96% of all participants, at which time the A1C level had decreased by an absolute amount of 0.24 and 0.15% in the intervention and control groups, respectively. The difference in A1C reduction for the intervention versus control group was 0.09% (95% CI -0.08 to 0.26; P = 0.3). No between-group differences in measures of quality of life, diabetes self-management behaviors, or clinical outcomes were observed.Providing computer-generated tailored feedback to registrants of a generic, community-based program that supports diabetes self-management does not lead to lower A1C levels or a better quality of life than participation in the community-based program (augmented by periodic A1C testing) alone.
Hypersensitivity in functional gastrointestinal disorders
Authors: F Azpiroz
Journal: Gut (2002)

The mechanisms by which neurons die after cerebral ischemia and related conditions <i>in vivo</i> are unclear, but they are thought to involve voltage-dependent Na<sup>+</sup> channels, glutamate receptors, and nitric oxide (NO) formation because selective inhibition of each provides neuroprotection. It is not known precisely what their roles are, nor whether they interact within a single cascade or in parallel pathways. These questions were investigated using an<i>in vitro</i> primary cell culture model in which striatal neurons undergo a gradual and delayed neurodegeneration after a brief (5&nbsp;min) challenge with the glutamate receptor agonist NMDA. Unexpectedly, NO was generated continuously by the cultures for up to 16&nbsp;hr after the NMDA exposure. Neuronal death followed the same general time course except that its start was delayed by ∼4 hr. Application of the NO synthase inhibitor nitroarginine after, but not during, the NMDA exposure inhibited NO formation and protected against delayed neuronal death. Blockade of NMDA receptors or of voltage-sensitive Na<sup>+</sup> channels [with tetrodotoxin (TTX)] during the postexposure period also inhibited both NO formation and cell death. The NMDA exposure resulted in a selective accumulation of glutamate in the culture medium during the period preceding cell death. This glutamate release could be inhibited by NMDA antagonism or by TTX, but not by nitroarginine. These data suggest that Na<sup>+</sup> channels, glutamate receptors, and NO operate interdependently and sequentially to cause neurodegeneration. At the core of the mechanism is a vicious cycle in which NMDA receptor stimulation causes activation of TTX-sensitive Na<sup>+</sup> channels, leading to glutamate release and further NMDA receptor stimulation. The output of the cycle is an enduring production of NO from neuronal sources, and this is responsible for delayed neuronal death. The same neurons, however, could be induced to undergo more rapid NMDA receptor-dependent death that required neither TTX-sensitive Na<sup>+</sup> channels nor NO.
Phase III Randomized Trial Comparing the Efficacy of Cediranib As Monotherapy, and in Combination With Lomustine, Versus Lomustine Alone in Patients With Recurrent Glioblastoma
Authors: Tracy T. Batchelor, Paul Mulholland, Bart Neyns, L. Burt Nabors, Mario Campone, Antje Wick, Warren Mason, Tom Mikkelsen, Surasak Phuphanich, Lynn S. Ashby, John DeGroot, Rao Gattamaneni, Lawrence Cher, Mark Rosenthal, Franz Payer, Juliane M. Jürgensmeier, Rakesh K. Jain, A. Gregory Sorensen, John Xu, Qi Liu, Martin van den Bent
Journal: Journal of Clinical Oncology (2013)

Purpose A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recentin in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan–vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma. Patients and Methods Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m 2 ); (3) lomustine (110 mg/m 2 ) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans. Results The primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone (hazard ratio [HR] = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90) or cediranib in combination with lomustine (HR = 0.76; 95% CI, 0.53 to 1.08; two-sided P = .16) versus lomustine based on independent or local review of postcontrast T1-weighted MRI. Conclusion This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma, although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects.
Proficiency testing of first- and second-line anti-tuberculosis drugs in Italy
Authors: Lanfranco Fattorini, Giovanni Battista Migliori, Antonio Cassone, Alessandro Mustazzolu, Giovanni Piccaro, Perla Filippini, Daniela Maria Cirillo, Emanuele Borroni
Journal: European Respiratory Journal (2012)

Proficiency testing of first-and second-line antituberculosis drugs in ItalyTo the Editors:The emergence of drug-resistant tuberculosis (TB) is an increasing threat to public health in industrialised countries; thus, it is important to supervise mycobacteriology laboratories by performing periodic proficiency of anti-TB drug susceptibility testing (DST).In 1994, the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Diseases developed a global project of anti-TB drug resistance surveillance to assist countries via a network of supranational reference laboratories (SRLs).Proficiency test (PT) results of firstline anti-TB drugs have been reported for the SRL network [1] and for some individual countries [2,3].
Dermatopathic Lymphadenitis Presenting as Lateral Breast Mass
Authors: A. Douglas Heymann
Journal: JAMA (1978)

Two cases of dermatopathic lymphadenitis involved external mammary lymph nodes and presented clinically as breast masses. The variable position and number of external mammary lymph nodes account for the difficulty in differentiating intrinsic breast pathological conditions of the lateral margin of the breast from lymphadenitis. Recent publicity may account for a lower threshold for detection of such lesions by patients as well as physicians. Dermatopathic lymphadenitis should be included in the differential diagnosis of persistent solid masses involving the lateral margin of the breast and should be confirmed by excisional biopsy.
Characterization of a mature bile duct antigen expressed on a subpopulation of biliary ductular cells but absent from oval cells
Authors: Li Yang, Ronald A. Faris, Douglas C. Hixson
Journal: Hepatology (1993)

Hybridomas were produced with immune spleen cells generated by immunization of Balb/c mice with oval cell antigen (OC.2)-positive 17-day fetal liver cells isolated on antibody-coated magnetic beads. A primary screen by indirect immunofluorescence on frozen sections of fetal and adult liver identified several hybridomas secreting antibodies reactive with bile ducts and oval cells. One of these recognized an epitope, designated BD1, which was expressed on intrahepatic bile ducts in 16-day fetal and adult rat liver and in liver from rats fed a choline-deficient diet containing ethionine and rats treated with 2-acetylaminofluorine, but was absent from morphologically defined oval cells induced by a choline-deficient diet containing ethionine or by 2-acetylaminofluorine. Double-labeling immunofluorescence analysis with monoclonal antibody BD1 and OV6, a monoclonal antibody that reacts uniformly with all bile ducts and oval cells, revealed that BD1 expression on the intrahepatic bile ductular cells of normal adult rat liver was heterogeneous with a major ductal cell population (60% to 70%) expressing high levels of BD1 and a minor ductal cell population (30% to 40%) displaying undetectable or low levels of BD1 expression. Analysis of fetal liver demonstrated the presence of BD1-positive cells at day 16 of gestation on ductlike structures in contact with portal mesenchyme, an observation suggesting that expression of BD1 was associated with commitment of hepatoblasts to a ductular lineage. Taken together, our findings suggest that oval cells may be derived from an antigenically distinct subpopulation of bile ductal cells. (Hepatology 1993;18:357-366).
Ratings of perceived exertion in braille: validity and reliability in production mode
Authors: John P Buckley, Roger G Eston, Julius Sim
Journal: British Journal of Sports Medicine (2000)

(a) To assess the validity and reliability of producing and reproducing a given exercise intensity during cycle ergometry using a braille version of Borg's standard 6-20 rating of perceived exertion (RPE) scale, and (b) to determine whether the exercise responses of blind participants, at a given produced RPE, were similar to those reported in recognised guidelines for sighted subjects.Ten healthy registered blind volunteer participants (four women, six men; mean (SD) age 23.2 (9.0) years) performed an initial graded exercise cycle test to determine maximal heart rate (HRMAx) and maximal oxygen uptake (VO2MAX). Three trials of three exercise bouts at RPEs 9, 11, and 13 were then performed in random order on three separate days of the same week, with expired air and heart rate measured continuously. Each exercise bout was followed by 10 minutes of rest. The validity of the scale as a means of producing different exercise intensities was assessed using a two factor (RPE x trial) repeated measures analysis of variance. Intertrial reliability was assessed using intraclass correlation coefficients (ICC) and the bias +/-95% limits of agreement (95%LoA) procedure.Participants reported no difficulty in using the braille RPE scale. When asked to produce exercise intensities equating to RPE 9, 11, and 13, they elicited mean %VO2MAX values of 47%, 53%, and 63% respectively. Analysis of variance showed no significant differences in either %HRMAx or %VO2MAX between trials at each of the three RPEs, but there was a significant difference (p<0.001) in both %HRMAx and %VO2MAX between the three RPE levels. All pairwise comparisons of the three different RPEs were significantly different (p<0.016). The ICC between the second and third trial for %HRMAx was significant (p <0.05) for all three RPEs. Similarly for %VO2MAX, the ICC was significant for RPE 9 and 11 but not 13. The 95%LoA decreased for both %HRMAx and %VO2MAX with each successive trial.Blind participants were successful in using a braille RPE scale to differentiate exercise intensity on a cycle ergometer. In every trial at RPE 13, all participants achieved %HRMAX and %VO2MAX levels, which fell within the recommendedrange for developing cardiorespiratory fitness. Using %HRMAx as a judge of intertrial reliability, the participants were able to repeat similar exercise intensities after two trials at each of the three RPEs (9, 11,13). The same was true for RPE 9 and 11, when %VO2MAX was used as a judge, but further trials were required to achieve similar reliability at RPE 13. A braille RPE scale can be used by healthy blind people during cycle ergometry, with similar effect to the visual analogue scale recommended for use in healthy sighted people.
LACK OF A CORRELATION BETWEEN CELL-MEDIATED IMMUNITY TO THE CARRIER AND THE CARRIER-HAPTEN HELPER EFFECT
Authors: F. Y. Liew, C. R. Parish
Journal: The Journal of Experimental Medicine (1974)

The relationship between cell-mediated immunity to the carrier and the carrier-hapten helper effect was studied in the rat by using three forms of the carrier which differed in their capacity to induce carrier-specific delayed-type hypersensitivity. The three carriers were polymerized flagellin (POL), flagellin (FIN), and acetoacetylated flagellin (AFIN), which induced FIN-specific delayed-type hypersensitivity in the order AFIN &amp;gt; FIN &amp;gt; POL. Helper cells for the anti-DNP antibody responses to a range of DNP-FIN conjugates appeared to be almost inversely related to cell-mediated immunity to the carrier, being in the order POL &amp;gt; FIN ⪖ AFIN. These differences occurred whether the carriers were injected in saline or FCA, but were less pronounced with the heavily DNP-conjugated flagellins.
Farber's disease (lysosomal acid ceramidase deficiency).
Authors: R A Jameson, P J Holt, J H Keen
Journal: Annals of the Rheumatic Diseases (1987)

The patient presented with progressive joint deformity, a hoarse voice, subsequent cachexia, and myoclonic seizures. She was first seen aged 22 months and died aged 6 years. A diagnosis of Farber9s disease was made by demonstrating a deficiency of acid ceramidase both in leucocytes and fibroblasts.