tbuckley/cabot-search huggingface dataset:
Can heart rate variation rule out sleep-disordered breathing in heart failure?
Authors: A. Vazir, M. Dayer, P. C. Hastings, H. F. McIntyre, M. Y. Henein, P. A. Poole-Wilson, M. R. Cowie, M. J. Morrell, A. K. Simonds
Journal: European Respiratory Journal (2006)

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne–Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea–hypopnoea index &gt;20 events·h −1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea–hypopnoea cut-off of 30 events·h −1 . In conclusion, these results suggest that spectral analysis of heart rate may be useful as a “rule-out test” for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.
Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells
Authors: Nicola Giuliani, Irma Airoldi
Journal: Clinical Cancer Research (2011)

Multiple myeloma is a monoclonal postgerminal center tumor that has phenotypic features of plasmablasts and/or plasma cells and usually localizes at multiple sites in the bone marrow. The pathogenesis of multiple myeloma is complex and dependent on the interactions between tumor cells and their microenvironment. Different cytokines, chemokines, and proangiogenic factors released in the tumor microenvironment are known to promote multiple myeloma cell growth. Here, we report recent advances on the role of 2 strictly related immunomodulatory cytokines, interleukin-27 (IL-27) and IL-23, in human normal and neoplastic plasma cells, highlighting their ability to (i) act directly against multiple myeloma cells, (ii) influence the multiple myeloma microenvironment by targeting osteoclast and osteoblast cells, and (iii) modulate normal plasma cell function. Finally, the therapeutic implication of these studies is discussed.
Prediction equations for single breath diffusing capacity (Tlco) in a middle aged caucasian population
Authors: B R Thompson, D P Johns, M Bailey, J Raven, E H Walters, M J Abramson
Journal: Thorax (2008)

<h3>Background:</h3> There are many reference equations for the measurement of single breath carbon monoxide diffusing capacity of the lung (Tlco). However, the testing methodologies vary and there are no well documented studies that have developed reference equations for Tlco and alveolar volume (Va) in middle aged and older populations. <h3>Aims:</h3> (1) Develop reference equations for Tlco in a middle aged population using the current American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines; (2) compare the equations with those commonly used in laboratories around the world. <h3>Methods:</h3> Healthy subjects (498 male and 474 female) aged 45–71 years were recruited as part of a larger epidemiological study. All participants completed a respiratory questionnaire and had spirometry and single breath Tlco (corrected for haemoglobin) measurements following ATS/ERS guidelines. <h3>Results:</h3> Mean age was 58 years for males and 57 years for females. For males, factors that predicted Tlco were: height, age, age×height interaction and being an ex-smoker. For females, factors that predicted Tlco were: height, age, weight and an age×height interaction. <h3>Conclusion:</h3> We have described new prediction equations for Tlco in a middle aged population that require validation in other populations.
Hematopoietic Stem Cells Need Two Signals to Prevent Apoptosis; Bcl-2 Can Provide One of These, Kitl/C-KIT Signaling the Other
Authors: Jos Domen, Irving L. Weissman
Journal: The Journal of Experimental Medicine (2000)

Growth factors can cause cells to proliferate, differentiate, survive, or die. Distinguishing between these responses is difficult in multicellular, multiparameter systems. Yet this is essential to understand the impact on cells like hematopoietic stem cells (HSCs), which have strict and still poorly understood growth factor requirements. Single cell plating in serum-free medium allows direct assessment of growth factor responses. The range of tested factors can be expanded if the cells are protected from growth factor deprivation–induced apoptosis. BCL-2 is overexpressed in HSCs of H2K-BCL-2 transgenic mice, protecting them from many apoptotic stimuli. The response of single wild-type and transgenic HSCs to stimulations with individual factors was tested. Surprisingly, we find that high level BCL-2 expression does not prevent rapid death under serum-free conditions, even though it does in the presence of serum. We also find that transgenic, but not wild-type cells, survive and proliferate rapidly in response to steel factor (Kit ligand). These studies show that two separate signals are necessary to prevent apoptosis in HSCs, and that Kit ligand by itself provides a strong proliferative stimulus to HSCs. However, the proliferative response does not result in self-renewal, but in differentiation to all known hematopoietic oligolineage progenitors.
Absence of transforming growth factor-β type II receptor is associated with poorer prognosis in HER2-negative breast tumours
Authors: C.E. Paiva, S.A. Drigo, F.E. Rosa, F.A. Moraes Neto, J.R.F. Caldeira, F.A. Soares, M.A.C. Domingues, S.R. Rogatto
Journal: Annals of Oncology (2009)
Genetic Polymorphisms and Protein Expression of NRF2 and Sulfiredoxin Predict Survival Outcomes in Breast Cancer
Authors: Jaana M. Hartikainen, Maria Tengström, Veli-Matti Kosma, Vuokko L. Kinnula, Arto Mannermaa, Ylermi Soini
Journal: Cancer Research (2012)

Abstract NRF2 activates several protective genes, such as sulfiredoxin (SRXN1), as a response to oxidative and xenobiotic stress. Defects in NRF2 pathway may increase cancer susceptibility. In tumor cells, activation of NRF2 may lead to chemo- and radioresistance and thus affect patient outcome. Nine single-nucleotide polymorphisms on NRF2 gene and eight on SRXN1 were genotyped in 452 patients with breast cancer and 370 controls. Protein expression of NRF2 and SRXN1 was studied in 373 breast carcinomas by immunohistochemistry. Statistical significance of the associations between genotypes, protein expression, clinicopathologic variables, and survival was assessed. A high level (&amp;gt;25%) of cytoplasmic NRF2 positivity was observed in 237 of 361 (66%) and SRXN1 positivity was observed in 82 of 363 (23%) cases. The NRF2 rs6721961 genotype TT was associated with increased risk of breast cancer [P = 0.008; OR, 4.656; confidence interval (CI), 1.350–16.063] and the T allele was associated with a low extent of NRF2 protein expression (P = 0.0003; OR, 2.420; CI, 1.491–3.926) and negative SRXN1 expression (P = 0.047; OR, 1.867; CI = 1.002–3.478). The NRF2 rs2886162 allele A was associated with low NRF2 expression (P = 0.011; OR, 1.988; CI, 1.162–3.400) and the AA genotype was associated with a worse survival (P = 0.032; HR, 1.687; CI, 1.047–2.748). The NRF2 rs1962142 T allele was associated with a low level of cytoplasmic NRF2 expression (P = 0.036) and negative sulfiredoxin expression (P = 0.042). The NRF2 rs2706110 AA genotype was associated with an increased risk of breast cancer, and the SRXN1 rs6053666 C allele was associated with a decrease in breast cancer risk (P = 0.011 and 0.017). NRF2 and SRXN1 genetic polymorphisms are associated with breast cancer risk and survival, implicating that mechanisms associated with reactive oxygen species and NRF2 pathway are involved in breast cancer initiation and progression. Cancer Res; 72(21); 5537–46. ©2012 AACR.
An in vivo experimental model for effects of topical retinoic acid in human skin
Authors: C.E.M. GRIFFITHS, L.J. FINKEL, M.G. TKANFAGLIA, T.A. HAMILTON, J.J. VOORHEES
Journal: British Journal of Dermatology (1993)

An occlusive patch‐test assay has been developed for assessment of topical retinoid action in human epidermis. Previous work with this assay has demonstrated marked epidermal hyperplasia in skin treated with topical all‐trans‐retinoic acid for 4 days and similar effects with the local irritant, sodium lauryl sulphate. To investigate the capabilities of this assay further, a time‐course and dose‐response were performed with all‐trans‐retinoic acid, and a comparison made with sodium lauryl sulphate. At no time, between 1 and 4 days, could the clinical or histological effects of 0.1% and 0.025% cream formulations of all‐trans‐retinoic acid be distinguished from each other. Epidermal hyperplasia was used to generate a 4‐day dose‐response for all‐trans‐retinoic acid at concentrations from 0. 00 l to 0. 025% dissolved in a 70% ethanol/30% propylene glycol vehicle. All‐trans‐retinoic acid could he successfully differentiated from sodium lauryl sulphate at 2 days by virtue of its greater ability to increase epidermal thickness, spongiosis and glycosaminoglycan deposition. It appears that although all‐trans‐retinoic acid and sodium lauryl sulphate produce similar epidermal histological changes at 4 days, significant differences at earlier time‐points suggest differing mechanisms of action. In addition, this in vivo human assay is able to provide potency ranking for doses of all‐trans‐retinoic acid, and may predict clinical efficacy of retinoids in improvement of acne and/or photodamage.
Interpretative and post-interpretative processes in sentence comprehension
Authors: Edward Gibson, Rose Roberts
Journal: Behavioral and Brain Sciences (1999)

We discuss several issues raised by Caplan &amp; Waters's distinction between interpretative and post-interpretative processes in sentence comprehension, including the nature and properties of the two systems, problems with measuring their respective capacities, and the relationship between the hypothesized separate-language-interpretation-resource (SLIR) and the general verbal working memory system that supports post-interpretive processing.
Pulmonary densities during anaesthesia. An experimental study on lung morphology and gas exchange
Authors: G Hedenstierna, H Lundquist, B Lundh, L Tokics, A Strandberg, B Brismar, C Frostell
Journal: European Respiratory Journal (1989)

The nature of dense areas in dependent lung regions regularly seen in anaesthetized humans was examined in a sheep model. During anaesthesia with muscle paralysis and mechanical ventilation dense areas in dependent lung regions could be seen by means of computerized tomography (CT). They had the same location and the same attenuation as in anaesthetized humans. Gas exchange impairment tended to increase in proportion to the size of the dense area on the CT scan. Microscopy showed that the densities in the sheep were atelectatic lung regions, with no or little interstitial oedema and only minor vascular congestion. The atelectatic lung tissue was sharply demarcated and the lung tissue in the immediate vicinity was well aerated, or even hyperinflated. Gravimetry showed the same amount of extravascular fluid and blood per unit lung weight in the atelectatic lung and in the aerated lung region. It is concluded that the densities appearing in dependent lung regions during anaesthesia are caused by atelectasis.
The Transcription Factor IRF8 Activates Integrin-Mediated TGF-β Signaling and Promotes Neuroinflammation
Authors: Yuko Yoshida, Ryusuke Yoshimi, Hiroaki Yoshii, Daniel Kim, Anup Dey, Huabao Xiong, Jeeva Munasinghe, Itaru Yazawa, Michael J. O’Donovan, Olga A. Maximova, Suveena Sharma, Jinfang Zhu, Hongsheng Wang, Herbert C. Morse, Keiko Ozato
Journal: Immunity (2014)
MATERNAL SMOKING DURING PREGNANCY AND THE RISK OF CHILDHOOD CANCER
Authors: P.A. McKinney, C.A. Stiller, Gisela Dahlquist, Stig Wall, J.D. Buckley, W.L. Hobbie, K. Ruccione, H.N. Sather, W.G. Woods, G.D. Hammond, FrederickP. Li, AllanS. Cunningham
Journal: The Lancet (1986)
cDNA cloning of a developmentally regulated hemocyanin subunit in the crustacean Cancer magister and phylogenetic analysis of the hemocyanin gene family
Authors: G Durstewitz, N B Terwilliger
Journal: Molecular Biology and Evolution (1997)

The complete cDNA sequence and protein reading frame of a developmentally regulated hemocyanin subunit in the Dungeness crab (Cancer magister) is presented. The protein sequence is aligned with 18 potentially homologous hemocyanin-type proteins displaying apparent sequence similarities. Functional domains are identified, and a comparison of predicted hydrophilicities, surface probabilities, and regional backbone flexibilities provides evidence for a remarkable degree of structural conservation among the proteins surveyed. Parsimony analysis of the protein sequence alignment identifies four monophyletic groups on the arthropodan branch of the hemocyanin gene tree: crustacean hemocyanins, insect hexamerins, chelicerate hemocyanins, and arthropodan prophenoloxidases. They form a monophyletic group relative to molluscan hemocyanins and nonarthropodan tyrosinases. Arthropodan prophenoloxidases, although functionally similar to tyrosinases, appear to belong to the arthropodan hexamer-type hemolymph proteins as opposed to molluscan hemocyanins and tyrosinases.
Effect of Organic Solvent Exposure on Chronic Kidney Disease Progression
Authors: Sophie Jacob, Michel He[Combining Acute Accent]ry, Jean-Claude Protois, Je[Combining Acute Accent]ro[Combining Circumflex Accent]me Rossert, Be[Combining Acute Accent]ne[Combining Acute Accent]dicte Stengel
Journal: Journal of the American Society of Nephrology (2006)

It has been suggested that solvent exposure may have a role in the progression of glomerulonephritis (GN) to ESRD, but this has never been tested with an appropriate cohort study design. A total of 338 non-ESRD patients with a first biopsy for primary GN between 1994 and 2001 were included: 194 IgA nephropathies (IgAN), 75 membranous nephropathies (MN), and 69 FSGS. ESRD, defined as an estimated GFR <15 ml/min per 1.73 m2 or dialysis, was registered during a mean follow-up period of 5 yr. Patients' lifelong solvent exposures before and after diagnosis were recorded by interview and assessed by industrial hygienist experts. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures. Overall, 15 and 14% of the patients had been exposed at a low and a high level before diagnosis, respectively. Forty-two with IgAN, 12 with MN, and 22 with FSGS reached ESRD. A graded relationship was observed for MN (age- and gender-adjusted HR [95% confidence interval] for low exposure versus none was 3.1 [0.5 to 18.2] and for high exposure versus none was 8.2 [1.9 to 34.7]) and for IgAN (1.6 [0.7 to 3.9] and 2.2 [1.0 to 4.8]) but not for FSGS. Solvent risk was mediated only partly by baseline proteinuria: Adjusted HR for high exposure versus none was 5.5 (1.3 to 23.9) for MN and 1.8 (0.8 to 3.9) for IgAN. In patients with IgAN, there was a trend in increasing HR with exposure duration before and its persistence after diagnosis. These findings support the hypothesized association of solvent exposure with the progression of GN to ESRD. They should prompt clinicians to give greater attention to patients' occupational exposures and possibly to consider professional reclassification.
A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF‐α
Authors: M. Laan, O. Prause, M. Miyamoto, M. Sjöstrand, A.M. Hytönen, T. Kaneko, J. Lötvall, A. Lindén
Journal: European Respiratory Journal (2003)

The T-cell cytokine interleukin (IL)-17 selectively accumulates neutrophils in murine airways in vivo and may thus constitute a link between activation of T-lymphocytes and accumulation of neutrophils. In this study, the authors evaluated the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in accumulation of neutrophils in the airways caused by IL-17 and tumour necrosis factor (TNF)-alpha. In vitro, human (h) IL-17 concentration-dependently stimulated the release of GM-CSF protein (enzyme-linked immunosorbent assay) in human bronchial epithelial cells (16HBE). IL-17 also time-dependently stimulated the release of GM-CSF protein in venous endothelial (human umbilical vein endothelial cells) cells in vitro. Co-stimulation with IL-17 plus the pro-inflammatory cytokine TNF-alpha potentiated the release of GM-CSF protein in 16HBE cells. hIL-17 also enhanced the expression of GM-CSF messenger ribonucleic acid in 16HBE cells (reverse transcriptase polymerase chain reaction), with a similar order of magnitude as TNF-alpha. Conditioned cell medium from bronchial epithelial cells co-stimulated with hIL-17 plus TNF-alpha prolonged survival (trypan blue exclusion) of human neutrophils in vitro and this effect was blocked by an anti-GM-CSF antibody. In vivo, local co-stimulation with mouse IL-17 plus TNF-alpha caused an additive potentiation of the accumulation of neutrophils in bronchoalveolar lavage fluid from mouse airways and this effect was blocked by an anti-GM-CSF antibody given systemically. In conclusion, granulocyte macrophage-colony stimulating factor is involved in the accumulation of neutrophils in the airways caused by interleukin-17 and tumour necrosis factor-alpha, probably via effects on both recruitment and survival of neutrophils.
ACTIVITY OF ANTI-INFLAMMATORY STEROIDS UPON FIBROBLASTS AND BONES
Authors: D. L. BERLINER, M. H. BARTLEY, G. H. KENNER, W. S. S. JEE
Journal: British Journal of Dermatology (1970)

Journal Article ACTIVITY OF ANTI‐INFLAMMATORY STEROIDS UPON FIBROBLASTS AND BONES Get access D. L. BERLINER, D. L. BERLINER Department of Anatomy, University of Utah, Salt Lake City, Utah, U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. H. BARTLEY, M. H. BARTLEY Department of Anatomy, University of Utah, Salt Lake City, Utah, U.S.A Search for other works by this author on: Oxford Academic Google Scholar G. H. KENNER, G. H. KENNER Department of Anatomy, University of Utah, Salt Lake City, Utah, U.S.A Search for other works by this author on: Oxford Academic Google Scholar W. S. S. JEE W. S. S. JEE Department of Anatomy, University of Utah, Salt Lake City, Utah, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue s6, 1 June 1970, Page 53, https://doi.org/10.1111/j.1365-2133.1970.tb08007.x Published: 01 June 1970
Relationship between the intensity of physical activity, inactivity, cardiorespiratory fitness and body composition in 7–10-year-old Dublin children
Authors: J Hussey, C Bell, K Bennett, J O’Dwyer, J Gormley
Journal: British Journal of Sports Medicine (2007)

Objective: To investigate the relationships between the time spent in specific intensities of activity and inactivity, cardiorespiratory fitness and body composition in children. Methods: A cross-sectional study was conducted in a random sample of schools. Height, weight and waist circumference were measured in 224 children aged 7–10 years. Cardiorespiratory fitness was estimated by the 20 m multistage running test, and physical activity was measured over 4 days by the RT3 (a triaxial accelerometer). Time each day spent in moderate and vigorous intensities of activity was calculated. Results: Twelve schools agreed to participate in the study. Body composition and fitness data were obtained for 224 children and activity data for 152 children. Boys were found to take part in about twice as much vigorous and hard activity as girls (mean (95% confidence interval) 64.3 (53.2 to 75.4) min in boys compared with 37 (33.1 to 40.9) min in girls; p&lt;0.001). In boys there was significant difference between those defined as normal, overweight and obese in the time spent in vigorous activity (p&lt;0.05), but no such difference was found in girls. A significant negative correlation between waist circumference and time spent in vigorous activity ( r = –0.31, p&lt;0.05) was found in boys but not in girls. Time spent sedentary was positively correlated with waist circumference in boys ( r = 0.33, p&lt;0.01) but not in girls. In both boys and girls there were significant negative correlations between fitness and both body mass index ( r = –0.274, p&lt;0.001) and waist circumference (boys: r = –0.503, p&lt;0.01; girls: r = –0.286, p&lt;0.01). Conclusion: In boys, body composition was inversely related to fitness and to vigorous activity and was positively related to inactivity. In girls, body composition was related to fitness but not to specific components of physical activity.
Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan–Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors
Authors: Josep Tabernero, Rastislav Bahleda, Rodrigo Dienstmann, Jeffrey R. Infante, Alain Mita, Antoine Italiano, Emiliano Calvo, Victor Moreno, Barbara Adamo, Anas Gazzah, Bob Zhong, Suso J. Platero, Johan W. Smit, Kim Stuyckens, Moitreyee Chatterjee-Kishore, Jordi Rodon, Vijay Peddareddigari, Feng R. Luo, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2015)

JNJ-42756493 is an orally administered pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor. This first-in-human study evaluates the safety, pharmacokinetics, and pharmacodynamics and defines the recommended phase II dose (RP2D) of JNJ-42756493.Eligible patients with advanced solid tumors received escalating doses of JNJ-42756493 from 0.5 to 12 mg administered continuously daily or JNJ-42756493 10 or 12 mg administered intermittently (7 days on/7 days off).Sixty-five patients were enrolled. The most common treatment-emergent adverse events included hyperphosphatemia (65%), asthenia (55%), dry mouth (45%), nail toxicity (35%), constipation (34%), decreased appetite (32%), and dysgeusia (31%). Twenty-seven patients (42%) experienced grade ≥ 3 treatment-emergent adverse events, and one dose-limiting toxicity of grade 3 ALT elevation was observed at 12 mg daily. Maximum-tolerated dose was not defined. Nine milligrams daily was considered as the initial RP2D; however, tolerability was improved with intermittent schedules, and 10 mg administered on a 7-days-on/7-days-off schedule was considered the final RP2D. Pharmacokinetics were linear, dose proportional, and predictable, with a half-life of 50 to 60 hours. Dose-dependent elevations in serum phosphate, a manifestation of pharmacodynamic effect, occurred in all patients starting at 4 mg daily. Among 23 response-evaluable patients with tumor FGFR pathway alterations, four confirmed responses and one unconfirmed partial response were observed in patients with glioblastoma and urothelial and endometrial cancer (all with FGFR2 or FGFR3 translocations); 16 patients had stable disease.JNJ-42756493 administered at 10 mg on a 7-days-on/7-days-off schedule achieved exposures at which clinical responses were observed, demonstrated pharmacodynamic biomarker activity, and had a manageable safety profile.