tbuckley/cabot-search huggingface dataset:
MORPHOLOGICAL CHANGES IN THE LUNGS OF RATS LIVING UNDER COMPRESSED AIR CONDITIONS
Authors: F. J. C. Smith, Granville A. Bennett, J. W. Heim, R. M. Thomson, C. K. Drinker
Journal: The Journal of Experimental Medicine (1932)

1. The alveolar cells in the lungs of young rats are greater in number and size than in old rats, a gradual transition to the state in the latter occurring from about the 4th to the 6th months of life. 2. On prolonged exposure to an environment having an 83.6 per cent oxygen tension, the cellularity of the alveoli is increased in both young and old animals, so that after 2 to 3 weeks it is impossible to distinguish them by morphological differences. Numerous mitotic figures are present in the alveolar cells. This hyperplasia and hypertrophy is a change which persists for months after the rats return to normal air. 3. Young rats do not develop the symptoms of acute oxygen poisoning, although some perivascular edema and dilatation of the lymphatics results on the 4th day of exposure, when intense acute pulmonary edema is present in old rats. 4. The mortality of acute oxygen poisoning is directly proportional to the age of the animals, although the majority of rats under 6 months of age survive this state and continue in apparent good health for as long as 72 days. All deaths during the acute stage in an 83.6 per cent oxygen tension occur on the 4th day of exposure. 5. After 1 month of exposure lesions are to be seen in the small arterioles of the lungs, consisting of a thickening and hyalinization of the walls with ultimate thrombosis of many. These vascular changes are identical with those seen in the arterioles of the kidney in chronic vascular nephritis. 6. Around the 45th day of exposure the large pulmonary arteries contain lesions in the media. The walls become loose meshed, thickened, and hyalinized, and hyaline cartilage formation is associated with these changes. 7. Reexposure of animals following an interval of 40 days in normal air subsequent to the first exposure of 72 days, does not produce any clinical or pathological changes. An adaptation to this toxic oxygen tension is produced during the first exposure, so that oxygen poisoning does not occur on second exposure. The increased cellularity of the alveolar walls persists. 8. The similarity in the morphological structure of the alveoli in young rats and in previously exposed old rats has a definite relationship to the adaptation that occurs to an oxygen tension of 83.6 per cent, preventing the development of acute oxygen poisoning on reexposure.
Ventilation-induced activation of the mitogen-activated protein kinase pathway
Authors: U. Uhlig, J.J. Haitsma, T. Goldmann, D.L. Poelma, B. Lachmann, S. Uhlig
Journal: European Respiratory Journal (2002)

Mechanical ventilation of patients can be a life-saving treatment, but also imposes additional stress on the lung. Mitogen-activated protein kinases (MAPK) represent a family of protein kinases that become phosphorylated and activated by many different forms of stress. Using Western blot analysis, the present study analysed the effects of high distending pressure ventilation on the activation of the MAPK extracellular signal-related kinases (ERK)-1/2, c-Jun amino-terminal kinases (JNK) and p38 kinase, and on the MAPK-activated transcription factors c-Jun, ETS-like protein (Elk)-1 and activating transcription factor (ATF)-2. In adult rats, ventilation with high pressure (45/10 peak inspiratory pressure/positive end-expiratory pressure in cmH 2 O) for 30 or 60 min did not affect arterial oxygenation, but resulted in enhanced phosphorylation of ERK-1/2, JNK, c-Jun, Elk-1 and ATF-2 compared to normally ventilated (13/3) rats. The activation of ERK-1/2 and JNK was located to cells resembling alveolar type II cells. In addition, high pressure ventilation enhanced phosphorylation of the inhibitor of nuclear factor (NF)-κB and nuclear translocation of the transcription factor NF-κB. In isolated perfused mouse lungs, the MAPK/ERK kinase inhibitor U0126 prevented ventilation-induced activation of ERK-1/2 and Elk-1, but had no effect on ventilation-induced cytokine release. The present authors conclude that mechanical ventilation triggers specific signalling pathways, such as the mitogen-activated protein kinase and the nuclear factor-κB pathways, which may contribute to pulmonary inflammation and proliferation.
Predicting Cardiovascular Risk Using Conventional vs Ambulatory Blood Pressure in Older Patients With Systolic Hypertension
Authors: Jan Staessen, Lutgarde Thijs, Robert Fagard, E T O'Brien, D Clement, P W de Leeuw, G Mancia, C Nachev, P Palatini, G Parati, J Tuomilehto, J Webster
Journal: JAMA (1999)

The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies.To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension.Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique.Family practices and outpatient clinics at primary and secondary referral hospitals.A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic.For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393).Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points.After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement.In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.
Family Planning as a Cost-Saving Preventive Health Service
Authors: Kelly Cleland, Jeffrey F. Peipert, Carolyn Westhoff, Scott Spear, James Trussell
Journal: New England Journal of Medicine (2011)

Nearly half the pregnancies that occur each year in the United States are unintended, according to the Guttmacher Institute. In 2001, an estimated 3.1 million pregnancies were reportedly unwanted or mistimed, and by 45 years of age, nearly half of U.S. women will have had an unintended pregnancy. Such pregnancies have far-reaching consequences for women, children, and families — ramifications that Brown and Eisenberg have enumerated:"With an unwanted pregnancy especially, the mother is more likely to seek prenatal care after the first trimester or not to obtain care. She is more likely to expose the fetus to harmful substances . . .
HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway
Authors: Stefanie Dimmeler, Alexandra Aicher, Mariuca Vasa, Christiane Mildner-Rihm, Klaudia Adler, Michaela Tiemann, Hartmut Rütten, Stephan Fichtlscherer, Hans Martin, Andreas M. Zeiher
Journal: Journal of Clinical Investigation (2001)

HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowering drugs and are well established to reduce morbidity and mortality from coronary artery disease. Here we demonstrate that statins potently augment endothelial progenitor cell differentiation in mononuclear cells and CD34-positive hematopoietic stem cells isolated from peripheral blood. Moreover, treatment of mice with statins increased c-kit+/Sca-1+–positive hematopoietic stem cells in the bone marrow and further elevated the number of differentiated endothelial progenitor cells (EPCs). Statins induce EPC differentiation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inhibitory effect of pharmacological PI3K blockers or overexpression of a dominant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given that statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-established beneficial effects of statins in patients with coronary artery disease.
Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis
Authors: T. Ishii, N. Keicho, S. Teramoto, A. Azuma, S. Kudoh, Y. Fukuchi, Y. Ouchi, T. Matsuse
Journal: European Respiratory Journal (2001)

Chronic obstructive pulmonary disease (COPD) and diffuse panbronchiolitis (DPB) are both characterized by chronic airflow limitation. Although the aetiology of these diseases is under investigation, it is commonly hypothesized that neutrophils have a major role in the disease pathogenesis. The variation of the genes related to chemotaxis of neutrophils may confer a risk for the development of both COPD and DPB. In the present report, the authors investigated the association between genetic variation that codes for the 416th and 420th amino acid of Gc-globulin, reported to be associated with chemotaxis of neutrophils, and susceptibility to COPD and DPB. Blood samples obtained from patients with COPD (n=63), DPB (n=82), and control subjects (n=82) were used for the genotyping assay. The proportion of GC*1F homozygotes was significantly higher in the COPD patients than the control subjects (COPD 36.5% <i>versus</i> control 20.7%), and the odds ratio for GC*1F homozygotes was 2.2 (95% confidence interval 1.1–4.6) for the COPD group. There was no difference on the distribution of the other genotypes (GC*1F-1S heterozygotes, GC*1S homozygotes, GC*2-1F heterozygotes, GC*2-1S heterozygotes and GC*2 homozygotes) or the allele frequencies among these groups. These findings suggest that the GC*1F gene polymorphism of Gc-globulin may be one of the risk factors for chronic obstructive pulmonary disease. However, no association between this polymorphism of Gc-globulin and susceptibility to diffuse panbronchiolitis was found.
Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A
Authors: Luke Hatchwell, Jason Girkin, Matthew D. Dun, Matthew Morten, Nicole Verrills, Hamish D. Toop, Jonathan C. Morris, Sebastian L. Johnston, Paul S. Foster, Adam Collison, Joerg Mattes
Journal: Journal of Allergy and Clinical Immunology (2014)
The Role of Nogo and the Mitochondria–Endoplasmic Reticulum Unit in Pulmonary Hypertension
Authors: Gopinath Sutendra, Peter Dromparis, Paulette Wright, Sébastien Bonnet, Alois Haromy, Zhengrong Hao, M. Sean McMurtry, Marek Michalak, Jean E. Vance, William C. Sessa, Evangelos D. Michelakis
Journal: Science Translational Medicine (2011)

The endoplasmic reticulum stress protein Nogo is a culprit in the mitochondrial defects that characterize pulmonary hypertension, pointing to therapeutic drug targets.
Five years' experience of PAS Port intravenous access system in adult cystic fibrosis
Authors: J Burdon, SP Conway, P Murchan, M Lansdown, RC Kester
Journal: European Respiratory Journal (1998)

An implantable venous access system provides a reliable and painless entry site for intravenous treatment. This study reports the authors' experience with such a system in adult patients with cystic fibrosis. Sixty five (87%) of 75 PAS Ports were placed successfully in 57 patients with cystic fibrosis. Because of early difficulties in advancing the catheter in patients whose veins had been traumatized by repeated courses of intravenous antibiotics, a technique was developed whereby venous entry was gained by direct subclavian puncture. This catheter insertion method was used in 53 (82%) attempts and the catheter was then passed by subcutaneous tunnelling to the port site on the ventral aspect of the upper arm. Fifty seven (88%) insertions were successful under local anaesthetic. The major early and late complications were iatrogenic pneumothorax (six cases) and infection (five cases), respectively. Late complications were more common when there was coexisting disease, e.g. diabetes mellitus, or an acute severe respiratory exacerbation, or when the Port was used for parenteral feeding. In conclusion, the PAS Port can be inserted safely by direct subclavian puncture. It was well tolerated and universally liked by the patients.
Gene Ontology: tool for the unification of biology
Authors: Michael Ashburner, Catherine A. Ball, Judith A. Blake, David Botstein, Heather Butler, J. Michael Cherry, Allan P. Davis, Kara Dolinski, Selina S. Dwight, Janan T. Eppig, Midori A. Harris, David P. Hill, Laurie Issel-Tarver, Andrew Kasarskis, Suzanna Lewis, John C. Matese, Joel E. Richardson, Martin Ringwald, Gerald M. Rubin, Gavin Sherlock
Journal: Nature Genetics (2000)
Efficacy and safety of thalidomide in patients with inflammatory manifestations of chronic granulomatous disease: A retrospective case series
Authors: Nicolas Noel, Nizar Mahlaoui, Stéphane Blanche, Felipe Suarez, Hélène Coignard-Biehler, Isabelle Durieu, Philippe Godeberge, Harry Sokol, Emilie Catherinot, Sylvain Poiree, Hugo Chapdelaine, Bertrand Dunogue, Christine Bodemer, Marc Lecuit, Alain Fischer, Olivier Lortholary, Olivier Hermine
Journal: Journal of Allergy and Clinical Immunology (2013)
NOTCH reprograms mitochondrial metabolism for proinflammatory macrophage activation
Authors: Jun Xu, Feng Chi, Tongsheng Guo, Vasu Punj, W.N. Paul Lee, Samuel W. French, Hidekazu Tsukamoto
Journal: Journal of Clinical Investigation (2015)

Metabolic reprogramming is implicated in macrophage activation, but the underlying mechanisms are poorly understood. Here, we demonstrate that the NOTCH1 pathway dictates activation of M1 phenotypes in isolated mouse hepatic macrophages (HMacs) and in a murine macrophage cell line by coupling transcriptional upregulation of M1 genes with metabolic upregulation of mitochondrial oxidative phosphorylation and ROS (mtROS) to augment induction of M1 genes. Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. As such, inhibition of the NOTCH pathway or Pdp1 knockdown abrogated glucose oxidation, mtROS, and M1 gene expression. Conditional NOTCH1 deficiency in the myeloid lineage attenuated HMac M1 activation and inflammation in a murine model of alcoholic steatohepatitis and markedly reduced lethality following endotoxin-mediated fulminant hepatitis in mice. In vivo monocyte tracking further demonstrated the requirement of NOTCH1 for the migration of blood monocytes into the liver and subsequent M1 differentiation. Together, these results reveal that NOTCH1 promotes reprogramming of mitochondrial metabolism for M1 macrophage activation.
TIME-DEPENDENT COVARIATES IN THE COX PROPORTIONAL-HAZARDS REGRESSION MODEL
Authors: Lloyd D. Fisher, D. Y. Lin
Journal: Annual Review of Public Health (1999)

▪ Abstract The Cox proportional-hazards regression model has achieved widespread use in the analysis of time-to-event data with censoring and covariates. The covariates may change their values over time. This article discusses the use of such time-dependent covariates, which offer additional opportunities but must be used with caution. The interrelationships between the outcome and variable over time can lead to bias unless the relationships are well understood. The form of a time-dependent covariate is much more complex than in Cox models with fixed (non–time-dependent) covariates. It involves constructing a function of time. Further, the model does not have some of the properties of the fixed-covariate model; it cannot usually be used to predict the survival (time-to-event) curve over time. The estimated probability of an event over time is not related to the hazard function in the usual fashion. An appendix summarizes the mathematics of time-dependent covariates.
Textbook of Respiratory Medicine
Journal: Thorax (1989)

Wegener's granulomatosis Positive (F) ANCA test Negative (F) Negative (D) Diagnostic specificity P(DIF) = 18/21 86% Diagnostic sensitivity P(IDF) = 214/219 98% Positive (D) 18 SI," s 2 1 ~~~~9 Nosological Nosological sensitivity specificity P(FID) = 18/23 P(F/D) = 214/217 78% 99%Nosological and diagnostic sensitivity and specificity of the test for antibodies to neutrophil cytoplasmic antigens (ANCA) used to assess the likelihood of disease according to the result of the test so long as the probabilities of disease in the diagnostic setting and in the patients studied for the paper are similar.On the other hand, nosological values of sensitivity and specificity are of limited direct relevance to the practising physician, who would need to convert these probabilities to the clinically relevant probabilities using Bayes's formula.This conversion is to a large extent dependent on the prior probability of disease in the clinical population studied and this is rarely known.There is a lot to be said for collecting data in a realistic clinical setting, as the authors have done, and quoting diagnostic specificity and sensitivity, rather than evaluating a new test in a group ofpatients who are known to have the disease in question and comparing this with the results in a group of normal people.In these circumstances the nosological value would be more appropriate.Taking the bright, coarsely granular pattern as positive, the authors found that the result of the test was positive in 18 patients with Wegener's granulomatosis and in three who did not have the disease.The result was negative in five patients who had active Wegener's granulomatosis and in 214 other patients, in most of whom, from the limited details given, Wegener's granulomatosis might have been initially suspec- ted but was not subsequently confirmed.On the basis ofthese figures (table) the nosological sensitivity is 78%, the nosological specificity 99%, the diagnostic sensitivity 98%, and the diagnostic specificity 86%.It would seem that the authors have quoted the nosological sensitivity with the diagnostic specificity.I would suggest that it would be more appropriate for them to have quoted the diagnostic sen- sitivity of98%-which, as an added bonus, looks even better than the quoted sensitivity of 78%.
Stimulating the GPR30 Estrogen Receptor with a Novel Tamoxifen Analogue Activates SF-1 and Promotes Endometrial Cell Proliferation
Authors: Benjamin C. Lin, Miyuki Suzawa, Raymond D. Blind, Sandra C. Tobias, Serdar E. Bulun, Thomas S. Scanlan, Holly A. Ingraham
Journal: Cancer Research (2009)

Abstract Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERα and ERβ nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERα or ERβ. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers. [Cancer Res 2009;69(13):5415–23]
Efficient destruction of human immunodeficiency virus in human serum by inhibiting the protective action of complement factor H and decay accelerating factor (DAF, CD55).
Authors: H Stoiber, C Pintér, A G Siccardi, A Clivio, M P Dierich
Journal: The Journal of Experimental Medicine (1996)

Activation of the human complement system leads to complement deposition on human immunodeficiency virus (HIV) and HIV-infected cells without causing efficient complement-mediated lysis. Even in the presence of HIV-specific antibodies, only a few particles are destroyed, demonstrating that HIV is intrinsically resistant to human complement. Here we report that, in addition to decay accelerating factor (DAF) being partially responsible, human complement factor H (CFH), a humoral negative regulator of complement activation, is most critical for this resistance. In the presence of HIV-specific antibodies, sera devoid of CFH (total genetic deficiency or normal human serum depleted of CFH by affinity chromatography) lysed free virus and HIV-infected but not uninfected cells. In the presence of CFH, lysis of HIV was only obtained when binding of CFH to gp41 was inhibited by a monoclonal antibody against a main CFH-binding site in gp41. Since CFH is an abundant protein in serum, and high local concentration of CFH can be obtained at the surface of HIV as the result of specific interactions of CFH with the HIV envelope, it is proposed that the resistance of HIV and HIV-infected cells against complement-mediated lysis in vivo is dependent on DAF and CFH and can be overcome by suppressing this protection. Neutralization of HIV may be achieved by antibodies against DAF and, more importantly, antibodies against CFH-binding sites on HIV envelope proteins.