tbuckley/cabot-search huggingface dataset:
Ways to shorten the lung clearance index measurement ΙΙ - How long to wash?
Authors: Florian Singer, Sophie Yammine, Chiara Abbas, Markus Roos, Philipp Latzin
Journal: European Respiratory Journal (2012)

Background Inert gas multiple-breath washout (MBW) derived lung clearance index (LCI) is a sensitive lung function parameter in subjects with mild cystic fibrosis (CF) lung disease, but rarely measured in clinical routine due to lack of available equipment and lengthy protocols. Using an available nitrogen (N2) MBW setup (Exhalyzer D, Eco Medics, Switzerland), we assessed shortened N2MBW protocols for LCI.

Methods Thirty-three school-aged children with CF and 21 controls performed triplicate N2MBW measurements. LCI was calculated as cumulative expired volume over functional residual capacity determined during N2MBW at 9% (1/11th) and 2.5% (1/40th, the current standard) end-tidal N2 concentration.

Results LCI differed significantly between healthy and CF children at both concentrations. The 9%-LCI was modestly associated with final 2.5%-LCI (R2 = 0.7) but took less time and was of similar diagnostic value. Comparing 9%- and 2.5%-LCI, mean (SD) test duration was 1.0 (0.4) and 2.2 (1.0) min; mean (95%CI) area under the receiver operating characteristic curve was 0.9 (0.8-0.9) and 0.9 (0.8-0.9); and upper limits of normal LCI (4.5 and 8.4) correctly classified 72% and 74% of children, respectively. Mean (SD) coefficient of variation was 5.7 (3.9)% for 9%-LCI and 5.7 (3.2)% for 2.5%-LCI.

Conclusion LCI determined at 9% end-tidal N2 concentration during N2MBW is repeatable, considerably faster, and identifies early CF lung disease with similar diagnostic value compared to the standard LCI in the current study population. This new shortened N2MBW protocol seems promising for time-saving LCI measurement in clinical routine.
Longitudinal Screening Algorithm That Incorporates Change Over Time in CA125 Levels Identifies Ovarian Cancer Earlier Than a Single-Threshold Rule
Authors: Charles W. Drescher, Chirag Shah, Jason Thorpe, Kathy O'Briant, Garnet L. Anderson, Christine D. Berg, Nicole Urban, Martin W. McIntosh
Journal: Journal of Clinical Oncology (2012)

Purpose Longitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels. Patients and Methods We retrospectively evaluated serial preclinical serum CA125 values measured annually in 44 incident ovarian cancer cases identified from participants in the PLCO (Prostate Lung Colorectal and Ovarian) Cancer Screening Trial to determine how frequently and to what extent the parametric empirical Bayes (PEB) longitudinal screening algorithm identifies ovarian cancer earlier than an ST rule. Results The PEB algorithm detected ovarian cancer earlier than an ST rule in a substantial proportion of cases. At 99% specificity, which corresponded to the ST-rule CA125 cutoff ≥ 35 U/mL that was used in the PLCO trial, 20% of cases were identified earlier by using the PEB algorithm. Among these cases, the PEB signaled abnormal CA125 values, on average, 10 months earlier and at a CA125 concentration 42% lower (20 U/mL) than the ST-rule cutoff. The proportion of cases detected earlier by the PEB algorithm and the earliness of detection increased as the specificity of the screening rule was reduced. Conclusion The PEB longitudinal algorithm identifies ovarian cancer earlier and at lower biomarker concentrations than an ST screening algorithm adjusted to the same specificity. Longitudinal biomarker assessment by using the PEB algorithm may have application for screening other solid tumors in which biomarkers are available.
Sodium Tolerance in Experimental Hypertension
Authors: SYDNEY M. FRIEDMAN, J. A. M. HINKE, DAVID F. HARDWICK, None L. FRIEDMAN
Journal: Circulation Research (1955)

A sodium tolerance test was applied to rats subjected to three diverse procedures for the production of experimental renal and hormonal hypertension. Sodium tolerance was impaired in all three types of hypertension to the extent that an accelerated excretion of the imposed sodium load occurred, although there was no change in the plasma sodium level. The disturbance was proportional to the height of the blood pressure but occurred even in those treated rats which remained normotensive.
Efficacy of chemotherapy as a first-line treatment in ocular adnexal extranodal marginal zone B-cell lymphoma
Authors: E.-K. Song, S.-Y. Kim, T.M. Kim, K.-W. Lee, T. Yun, I.-I. Na, H. Shin, S.H. Lee, D.W. Kim, S.I. Khwarg, D.S. Heo
Journal: Annals of Oncology (2007)
Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia
Authors: M Pfirrmann, M Baccarani, S Saussele, J Guilhot, F Cervantes, G Ossenkoppele, V S Hoffmann, F Castagnetti, J Hasford, R Hehlmann, B Simonsson
Journal: Leukemia (2015)
Mechanism of Hypokalemia in Magnesium Deficiency
Authors: Chou-Long Huang, Elizabeth Kuo
Journal: Journal of the American Society of Nephrology (2007)

Magnesium deficiency is frequently associated with hypokalemia. Concomitant magnesium deficiency aggravates hypokalemia and renders it refractory to treatment by potassium. Herein is reviewed literature suggesting that magnesium deficiency exacerbates potassium wasting by increasing distal potassium secretion. A decrease in intracellular magnesium, caused by magnesium deficiency, releases the magnesium-mediated inhibition of ROMK channels and increases potassium secretion. Magnesium deficiency alone, however, does not necessarily cause hypokalemia. An increase in distal sodium delivery or elevated aldosterone levels may be required for exacerbating potassium wasting in magnesium deficiency.
Involvement of p21WAF1/Cip1, p27Kip1, and p18INK4c in troglitazone-induced cell-cycle arrest in human hepatoma cell lines
Authors: Hironori Koga, Shotaro Sakisaka, Masaru Harada, Toshiyuki Takagi, Shinichiro Hanada, Eitaro Taniguchi, Takumi Kawaguchi, Kurumi Sasatomi, Rina Kimura, Osamu Hashimoto, Takato Ueno, Hirohisa Yano, Masamichi Kojiro, Michio Sata
Journal: Hepatology (2001)

Peroxisome proliferator-activated receptor γ (PPARγ) regulates cell growth and differentiation. Recent evidence has suggested that PPARγ ligands had anti–tumor effects through inhibiting cell growth and inducing cell differentiation in several types of malignant neoplasm. In the present study, we investigated: 1) the expression of PPARγ in both human hepatoma cell lines and 5 resected human hepatocellular carcinoma (HCC) tissues; 2) the growth–inhibitory effect of troglitazone, a PPARγ ligand, on those hepatoma cells; and 3) the molecular mechanisms of troglitazone–induced cell–cycle arrest. Five hepatoma cell lines, HLF, HuH–7, HAK–1A, HAK–1B, and HAK–5, were used. The mRNA expression levels of PPARγ, p21 WAF1/Cip1 , and p27 Kip1 were determined by real–time quantitative reverse transcription–polymerase chain reaction. The expression of cell cycle-regulating proteins, such as p21, p27, p18 INK4c , cyclin E, and pRb, was examined using Western blotting. PPARγ was constitutively expressed in all the cell lines and the HCC tissues used in this study. A cytostatic effect of troglitazone was found in those cell lines, and this inhibition of cell growth was dosage–dependent. G0/G1 arrest was apparently demonstrated in flow cytometric analysis in HLF, HAK–1A, HAK–1B, and HAK–5, all of which showed an increased expression of p21 protein. However, HuH–7, lacking p21 protein expression, did not demonstrate clear arrest in the cell–cycle analysis. HLF, which was deficient in the protein product of the retinoblastoma tumor–suppressor gene (pRb), responded most profoundly to troglitazone, showing an increased expression in not only p21, but also in p27 and in p18. These findings suggested that p21, p27, and p18 might be involved in troglitazone–induced cell–cycle arrest in human hepatoma cells.
Regional chest wall volumes during exercise in chronic obstructive pulmonary disease
Authors: A Aliverti
Journal: Thorax (2004)

Dynamic hyperinflation of the lungs impairs exercise performance in chronic obstructive pulmonary disease (COPD). However, it is unclear which patients are affected by dynamic hyperinflation and how the respiratory muscles respond to the change in lung volume.Using optoelectronic plethysmography, total and regional chest wall volumes were measured non-invasively in 20 stable patients with COPD (mean (SD) forced expiratory volume in 1 second 43.6 (11.6)% predicted) and dynamic hyperinflation was tracked breath by breath to test if this was the mechanism of exercise limitation. Resting ventilation, breathing pattern, symptoms, rib cage and abdominal volumes were recorded at rest and during symptom limited cycle ergometry. Pleural, abdominal, and transdiaphragmatic pressures were measured in eight patients.End expiratory chest wall volume increased by a mean (SE) of 592 (80) ml in 12 patients (hyperinflators) but decreased by 462 (103) ml in eight (euvolumics). During exercise, tidal volume increased in euvolumic patients by reducing end expiratory abdominal volume while in hyperinflators tidal volume increased by increasing end inspiratory abdominal and rib cage volumes. The maximal abdominal pressure was 22.1 (9.0) cm H(2)O in euvolumic patients and 7.6 (2.6) cm H(2)O in hyperinflators. Euvolumic patients were as breathless as hyperinflators but exercised for less time and reached lower maximum workloads (p<0.05) despite having better spirometric parameters and a greater expiratory flow reserve.Dynamic hyperinflation is not the only mechanism limiting exercise performance in patients with stable COPD. Accurate measurement of chest wall volume can identify the different patterns of respiratory muscle activation during exercise.
Endothelial Precursor Cell Migration During Vasculogenesis
Authors: Annette Schmidt, Klara Brixius, Wilhelm Bloch
Journal: Circulation Research (2007)

Migration of endothelial precursor cells (so-called "angioblasts" in embryos and "endothelial progenitor cells" in adults) during vasculogenesis is a requirement for the formation of a primary vascular plexus. The migration is initiated by the change of endothelial precursors to their migratory phenotype. The endothelial precursor cells are then guided to the position where the primary vascular plexus is formed. Migration is stopped by the reversion of the cells to their nonmigratory phenotype. A combination of regulatory mechanisms and factors controls this process. These include gradients of soluble factors, extracellular matrix-cell interaction and cell-cell interaction. In this review, we give an overview of the regulation of angioblast migration during embryonic vasculogenesis and its relationship to the migration of endothelial progenitors during postnatal vascular development.
Bone metabolism is altered in preclinical rheumatoid arthritis: Table 1
Authors: Dirkjan van Schaardenburg, Markus M J Nielen, Willem F Lems, Jos W R Twisk, Henk W Reesink, Rob J van de Stadt, Irene E van der Horst-Bruinsma, Margret H M T de Koning, Moud R Habibuw, Ben A C Dijkmans
Journal: Annals of the Rheumatic Diseases (2010)

Radiographic damage and its progression in early rheumatoid arthritis (RA) can be predicted by markers and regulators of bone metabolism. Studies of bone formation in RA patients measuring osteocalcin or the N-terminal telopeptide of type I procollagen (P1NP) have produced varying results, whereas measurements of bone resorption using serum or urine C-terminal crosslink of type I collagen (β-CTX) mostly show increased values.1,–,3 RA patients often have elevated serum levels of the osteoclast-activating cytokine receptor activator of nuclear factor κB ligand (RANKL), as well as of osteoprotegerin, which prevents osteoclast activation.4

We previously reported increased levels of autoantibodies and acute phase reactants …
Relationship between the acid-induced cough response and airway responsiveness and obstruction in children with asthma.
Authors: T Shimizu, H Mochizuki, K Tokuyama, A Morikawa
Journal: Thorax (1996)

BACKGROUND: In children with asthma little is known about the direct effect of the bronchoconstrictor and bronchodilator response on the cough threshold, or the relationship between bronchial responsiveness and the cough threshold. A study was undertaken to determine the effect of histamine-induced bronchoconstriction and salbutamol-induced bronchodilatation on the cough threshold in response to inhaled acetic acid, and to examine the relationship between the acetic acid cough threshold and bronchial hyperresponsiveness to histamine in children with asthma. METHODS: Nineteen children with asthma (16 boys) of mean (SE) age 10.6 (0.6) years were enrolled in the study. On day 1 each underwent a histamine inhalation challenge to determine the provocative concentration causing a fall in forced expiratory volume in one second (FEV1) of more than 20% (PC20) as an index of individual bronchial hyperresponsiveness. On day 2 the acetic acid cough threshold was determined before and just after the inhalation of the PC20 concentration of histamine, and then salbutamol (1 mg/m2) was inhaled to relieve the bronchoconstriction. Ten of the 19 patients (eight boys) of mean age 12.2 (0.7) years also tried acetic acid inhalation challenge just after salbutamol inhalation. RESULTS: There was no relationship between the bronchial responsiveness to histamine and acetic acid cough threshold in these patients. The acetic acid cough threshold after histamine inhalation was similar to that before histamine, although FEV1 decreased after histamine. In the 10 patients who also tried acetic acid inhalation challenge after salbutamol the cough threshold did not change. CONCLUSIONS: These findings suggest that acid-induced cough sensitivity and bronchomotor tone are independently regulated in children with asthma.
Case management of HIV-infected severely malnourished children: challenges in the area of highest prevalence
Authors: Geert Tom Heikens, James Bunn, Beatrice Amadi, Mark Manary, Meera Chhagan, James A Berkley, Nigel Rollins, Paul Kelly, Charlotte Adamczick, Kathryn Maitland, Andrew Tomkins
Journal: The Lancet (2008)
Respiratory Disorders and Allergy Skin-Test Reactions
Authors: BENJAMIN BURROWS
Journal: Annals of Internal Medicine (1976)

This study examines the relations of allergy skin-test reactivity, assessed by prick testing, to a variety of respiratory symptoms, findings, and diagnoses in a general population sample consisting of more than 3000 subjects. The independent and combined relations of skin-test reactivity and cigarette smoking are reported. Prevalences of asthma and allergic rhinitis are closely related to the severity of skin-test reactions; all of the 39 subjects with the largest skin-test reactions observed have had one or both of these conditions. A variety of other respiratory findings, not generally considered allergic in nature, are also related to skin-test reactivity, especially in children and in young to middle-aged adults. In subjects 15 to 54 years of age, an atopic predisposition, as manifested by reactions to allergy skin tests, appears to be associated with an increased susceptibility to the bronchoconstrictor effects of cigarette smoking and to recurrent chest infections. It is suggested that an atopic predisposition relatively early in life may be a risk factor for the later development of chronic obstructive lung diseases.
Beta-adrenergic agonists stimulate the synthesis of noncontractile but not contractile proteins in cultured myocytes isolated from adult rat heart.
Authors: I Dubus, J L Samuel, F Marotte, C Delcayre, L Rappaport
Journal: Circulation Research (1990)

The effect of catecholamines on adult myocardial protein synthetic activity was studied by use of an experimental model of isolated adult rat cardiac myocytes maintained in culture for 1-6 days. During this period, the majority of myocytes retained their rod-shaped morphology, but the cell number decreased progressively (50% of the initial density after 2 days in culture). Between day 1 and day 3 in culture, the specific synthetic activities of total proteins and of electrophoretically purified myosin heavy chain and actin ([14C] phenylalanine incorporation into protein, in disintegrations per minute per microgram protein) decreased (-19%,-32%, and -73%, respectively). Addition of isoproterenol or norepinephrine (10 nM) from the onset of the culture for 3 days increased the specific activity of both total and noncontractile proteins (greater than 20%) but had no effect on the specific activity of myosin heavy chain and actin when compared with 3-day cultured control cells. beta-Adrenergic receptors are specifically required to mediate this increase in total protein synthesis. This finding was demonstrated by the inhibitory effects of propranolol; neither prazosin nor yohimbine showed any effect. The pattern of synthesized protein during adrenergic stimulation was qualitatively evaluated by use of [35S]methionine incorporation and gel electrophoresis. The general pattern of labeled proteins did not differ significantly from that of control cells; this occurrence suggests that isoproterenol harmoniously stimulates the synthesis of noncontractile proteins. These findings demonstrate that low doses of beta-adrenergic agonists have an anabolic effect on adult cardiac quiescent myocytes that do not affect the major contractile proteins. Regulation of myofibrillar protein synthesis may be more dependent on myocyte contractile activity.
Differential mortality risk of postprocedural creatine kinase-MB elevation following successful versus unsuccessful stent procedures
Authors: Allen Jeremias, Donald S. Baim, Kalon K.L. Ho, Manish Chauhan, Joseph P. Carrozza, David J. Cohen, Jeffrey J. Popma, Richard E. Kuntz, Donald E. Cutlip
Journal: Journal of the American College of Cardiology (2004)
Prognostic Factors for Overall Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor–Targeted Agents: Results From a Large, Multicenter Study
Authors: Daniel Y.C. Heng, Wanling Xie, Meredith M. Regan, Mark A. Warren, Ali Reza Golshayan, Chakshu Sahi, Bernhard J. Eigl, J. Dean Ruether, Tina Cheng, Scott North, Peter Venner, Jennifer J. Knox, Kim N. Chi, Christian Kollmannsberger, David F. McDermott, William K. Oh, Michael B. Atkins, Ronald M. Bukowski, Brian I. Rini, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2009)

There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy.Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS.The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73.This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
Augmented TLR9-induced Btk activation in PIR-B–deficient B-1 cells provokes excessive autoantibody production and autoimmunity
Authors: Tomohiro Kubo, Yuki Uchida, Yuko Watanabe, Masahiro Abe, Akira Nakamura, Masao Ono, Shizuo Akira, Toshiyuki Takai
Journal: The Journal of Experimental Medicine (2009)

Pathogens are sensed by Toll-like receptors (TLRs) expressed in leukocytes in the innate immune system. However, excess stimulation of TLR pathways is supposed to be connected with provocation of autoimmunity. We show that paired immunoglobulin (Ig)-like receptor B (PIR-B), an immunoreceptor tyrosine-based inhibitory motif–harboring receptor for major histocompatibility class I molecules, on relatively primitive B cells, B-1 cells, suppresses TLR9 signaling via Bruton's tyrosine kinase (Btk) dephosphorylation, which leads to attenuated activation of nuclear factor κB p65RelA but not p38 or Erk, and blocks the production of natural IgM antibodies, including anti-IgG Fc autoantibodies, particularly rheumatoid factor. The autoantibody production in PIR-B–deficient (Pirb−/−) mice was further augmented in combination with the Faslpr mutation, which might be linked to the development of autoimmune glomerulonephritis. These results show the critical link between TLR9-mediated sensing and a simultaneously evoked, PIR-B–mediated inhibitory circuit with a Btk intersection in B-1 cells, and suggest a novel way toward preventing pathogenic natural autoantibody production.
Histogenetic divisions, developmental mechanisms, and cortical evolution
Authors: Loreta Medina
Journal: Behavioral and Brain Sciences (2003)

An alteration in the developmental mechanisms that regulate telencephalic patterning or pallial growth may have led to an enlargement of the dorsal pallium during evolution, and to the origin of isocortex. Developmental mechanisms that may have produced a pallial enlargement, and the parallelism of this event with the enlargement of the dorsal thalamus during evolution are discussed.