tbuckley/cabot-search huggingface dataset:
Intrasubject variability of maximal expiratory flow volume curve.
Authors: G M Cochrane, F Prieto, T J Clark
Journal: Thorax (1977)

Analysis of airflow in the terminal portion of the maximal expiratory flow volume curve has been suggested as a useful test for the early diagnosis of chronic airways obstruction. Whether such an analysis can identify early disease, and whether any subsequent action can prevent the progress of chronic airways obstruction, is unknown and will require prospective studies. As a precursor of such a study we have tried to establish the intrasubject variability of those tests of forced expiration which may be used for screening. We therefore measured expiratory flow volume curves of five healthy males and five healthy females aged 20-30 years as this is an age-group in which early detection of airways obstruction may be of value. Flow volume curves were obtained on the same day of the week for six weeks, and on three separate days during this period we carried out three flow volume curves every hour from 9 am to 6 pm. The data were subjected to analysis of variance to determine the variability of each measurement. Data were collected from forced expired volume in one second (FEV1) forced vital capacity (FVC), maximum expiratory flow rates at 50% and 75% of expired vital capacity, and forced expiratory time (FET). The results showed no consistent pattern of diurnal variation over the working day. The variation in any subject for FEV1 and FVC over the study period was considerably less than variations detected in the maximal expiratory flow rates at 50% and 75% of the expired vital capacity and FET. Our results suggest that the intrasubject variation found in flow rates of the terminal portion of the maximal expiratory flow volume curve and forced expiratory time may limit the usefulness of these tests in detecting early airways obstruction. FEV1 and FVC are more reproducible tests and are therefore particularly suited for cross-sectional screening. The more sensitive maximal expiratory flow volume curve may, however, be more useful for long-term studies in individuals when the onset of disease is sought, or for short-term challenge studies requiring the most sensitive index of change in airway characteristics.
In defense of the tenure system
Authors: Gary Greenberg, Dorothy K. Billings
Journal: Behavioral and Brain Sciences (2006)

We do not dispute the findings of Ceci et al.'s study, though they are based on survey research which does not always reflect real-life experiences. We report on cases we have defended on the basis of the tenure system, few of which mirror the situations reported in the target article. We end with a strong defense of the tenure system in the modern university.
Prolonged Starvation as Treatment for Severe Obesity
Authors: Ernst J. Drenick, Marion E. Swendseid, William H. Blahd, Stewart G. Tuttle
Journal: JAMA (1964)

Eleven obese, ambulatory patients were starved for periods of 12 to 117 days. Only water and vitamins were consumed. Weight losses averaged 0.91 pounds (0.41 kg) daily. Hunger was virtually absent. Complications which developed during starvation were severe orthostatic hypotension in three cases; severe normocytic, normochromic anemia in one case; and gouty arthritis in two cases. With refeeding all ill effects were promptly reversed. Serum electrolytes, lipids, proteins, and amino acids remained unchanged during starvation. Serum uric acid increased; blood glucose levels fell in some cases. Considerable amounts of body protein and potassium were lost. Prolonged starvation is not advised for obese patients with a history of ischemic cardiovascular or cerebral disease, with history of gout, or with hepatic diseahypo
Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years
Authors: V. W.-S. Wong, G. L.-H. Wong, P. C.-L. Choi, A. W.-H. Chan, M. K.-P. Li, H.-Y. Chan, A. M.-L. Chim, J. Yu, J. J.-Y. Sung, H. L.-Y. Chan
Journal: Gut (2010)

<h3>Background</h3> Patients with non-alcoholic steatohepatitis (NASH) have increased mortality and liver-related complications. In contrast, simple steatosis is considered benign and non-progressive. <h3>Objective</h3> To investigate disease progression in patients with different degrees of non-alcoholic fatty liver disease (NAFLD) activity. <h3>Design</h3> Prospective longitudinal hospital-based cohort study. <h3>Patients</h3> Fifty-two patients (age 44±9 years) with biopsy-proven NAFLD had liver biopsies repeated at month 36. <h3>Results</h3> Among 13 patients with simple steatosis at baseline, 2 (15%) had a normal liver at month 36, 3 (23%) continued to have simple steatosis, 5 (39%) developed borderline NASH and 3 (23%) developed NASH. Among 22 patients with borderline NASH at baseline, 4 (18%) had simple steatosis and 13 (59%) had borderline NASH at month 36, while 5 (23%) developed NASH. Among 17 patients with NASH at baseline, 10 (59%) continued to have NASH and 6 (35%) had borderline NASH at month 36. Only 1 (6%) patient regressed to simple steatosis. Overall, 14 (27%) patients had fibrosis progression, 25 (48%) had static disease, and 13 (25%) had fibrosis regression. Reduction in body mass index and waist circumference was independently associated with non-progressive disease activity and fibrosis. The baseline serum levels and month 36 changes in adiponectin, tumour necrosis factor α, interleukin 6 and leptin were not associated with disease progression. Serum cytokeratin-18 fragment level reflected disease activity and its change correlated with the change in NAFLD activity score (R=0.51, p&lt;0.001). <h3>Conclusions</h3> Patients with simple steatosis may still develop NASH and fibrosis progression. Weight reduction is associated with non-progressive disease. All patients with NAFLD should undergo periodic assessment and lifestyle modification.
Simvastatin suppresses RANTES-mediated neutrophilia in polyinosinic–polycytidylic acid-induced pneumonia
Authors: Chang Seok Lee, Eun Hee Yi, Jin-Ku Lee, Cheolhee Won, Young Ju Lee, Min Kyung Shin, Young Mok Yang, Myung-Hee Chung, Jung Weon Lee, Sang-Hyun Sung, Sang-Kyu Ye
Journal: European Respiratory Journal (2012)

Recently, statins have been shown to have anti-inflammatory effects on lung inflammatory diseases. However, the mechanisms of action of simvastatin in viral pneumonia have yet to be elucidated, although viral infection remains a considerable health threat. In this study, we hypothesised that simvastatin inhibits polyinosinic-polycytidylic acid (poly I:C)-induced airway inflammation, such as RANTES (regulated on activation, normal T-cell expressed and secreted) expression and inflammatory cell recruitment. In bronchial cells, the effect of simvastatin on poly I:C-induced RANTES expression and signal transducer and activator of transcription (STAT)3-mediated signal transduction was determined using an ELISA and short hairpin (sh)RNA system. In a poly I:C-induced pneumonia mouse model, immunological changes in the lungs after simvastatin inhalation, such as inflammatory cell recruitment and cytokine/chemokine release, were examined. In poly I:C-stimulated bronchial cells, RANTES secretion was increased by STAT3 activation, and simvastatin suppressed poly I:C-induced STAT3 activation, resulting in inhibition of RANTES expression. In BALB/c mice stimulated with inhaled poly I:C, RANTES expression and neutrophil infiltration into the airway were elevated. However, simvastatin treatment attenuated STAT3 activation, RANTES release and subsequent neutrophilia in the lungs. These findings suggest that simvastatin inhibits airway inflammation, but there are other mechanisms that need to be fully elucidated.
Inhibition of Fibroblast Growth Factor 19 Reduces Tumor Growth by Modulating β-Catenin Signaling
Authors: Rama Pai, Debra Dunlap, Jing Qing, Iman Mohtashemi, Kathy Hotzel, Dorothy M. French
Journal: Cancer Research (2008)

Fibroblast growth factors (FGF) play important roles in development, angiogenesis, and cancer. FGF19 uniquely binds to FGF receptor 4 (FGFR4). Our previous study has shown that FGF19 transgenic tumors have an activated Wnt-pathway phenotype. Wnt signaling is implicated in initiating or promoting FGF signaling in various cell types and organs. In this study, we examined whether FGF19 or inhibition of FGF19 affects the beta-catenin signaling pathway using human colon cancer cell lines (HCT116, Colo201). Our results show that FGF19 increases tyrosine phosphorylation of beta-catenin and causes loss of beta-catenin-E-cadherin binding. FGF19 increases p-GSK3beta and active beta-catenin levels and anti-FGF19 antibody (1A6) treatment abrogates this effect of FGF19. Anti-FGF19 antibody treatment increases S33/S37/T41 phosphorylation and ubiquitination of beta-catenin. Ion-trap mass spectrometric analysis confirmed that 1A6 increases phosphorylation of beta-catenin in the NH(2) terminus. Using HCT116-paired beta-catenin knockout cells, we show that FGF19 induces TCF/LEF reporter activity in parental (WT/Delta45) and in WT/--but not in mutant (-/Delta45) cells, and that inhibition of endogenous FGF19 reduces this reporter activity, indicating that wild-type beta-catenin is accessible for modulation. FGFR4 knockdown using inducible short hairpin RNA significantly reduces the colony-forming ability in vitro and tumor growth in vivo. Although cleaved caspase-3 immunoreactivity remains unchanged, the number of ki67-positive nuclei is reduced in FGFR4 knockdown tumor xenograft tissues. Consistent with the reduced beta-catenin activation, Taqman analyses show that FGF19/FGFR4 inhibition reduced beta-catenin target gene (cyclin D1, CD44, c-jun, Cox-2, UPAR) expression. These findings highlight that FGF19/FGFR4 cross-talk with beta-catenin and that pathway intervention reduces tumor growth.
Let Them Fall Where They May: Congruence Analysis in Massive Phylogenetically Messy Data Sets
Authors: J. W. Leigh, K. Schliep, P. Lopez, E. Bapteste
Journal: Molecular Biology and Evolution (2011)

Interest in congruence in phylogenetic data has largely focused on issues affecting multicellular organisms, and animals in particular, in which the level of incongruence is expected to be relatively low. In addition, assessment methods developed in the past have been designed for reasonably small numbers of loci and scale poorly for larger data sets. However, there are currently over a thousand complete genome sequences available and of interest to evolutionary biologists, and these sequences are predominantly from microbial organisms, whose molecular evolution is much less frequently treelike than that of multicellular life forms. As such, the level of incongruence in these data is expected to be high. We present a congruence method that accommodates both very large numbers of genes and high degrees of incongruence. Our method uses clustering algorithms to identify subsets of genes based on similarity of phylogenetic signal. It involves only a single phylogenetic analysis per gene, and therefore, computation time scales nearly linearly with the number of genes in the data set. We show that our method performs very well with sets of sequence alignments simulated under a wide variety of conditions. In addition, we present an analysis of core genes of prokaryotes, often assumed to have been largely vertically inherited, in which we identify two highly incongruent classes of genes. This result is consistent with the complexity hypothesis.
NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory
Authors: Steven E. Hyman, Robert C. Malenka, Eric J. Nestler
Journal: Annual Review of Neuroscience (2006)

Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons. Here we review progress in identifying candidate mechanisms of addiction.
Necropsy incidence of emphysema in Uganda
Authors: A. W. Jones, P. J. Madda
Journal: Thorax (1974)

<b>Jones, A. W. and Madda, P. J. (1974).</b><i>Thorax</i>, <b>29</b>, 195-198. <b>Necropsy incidence of emphysema in Uganda.</b> The incidence and types of pulmonary emphysema and the degree of dust pigmentation of the lungs were investigated in a series of 183 necropsies in Uganda. Emphysema was present in 43 (23·5%) lungs. Panlobular or centrilobular emphysema was found in 17 cases, an overall incidence of 9·3% (10·4% of the 135 males and 6·3% of the 48 females). It was generally of mild degree and the mean lung involvement, as assessed by a point counting method, was 9·2% in the 17 cases described above. Panlobular and centrilobular emphysema occurred in the older age groups; 13 of the 17 cases were 50 years old or more. The remaining 26 cases consisted of irregular (scar) emphysema which occurred in trace amounts (less than 1%). Dust pigmentation was present in all 17 cases of emphysematous lungs and was generally more severe than in the non-emphysematous lungs. The incidence of emphysema in this predominantly rural population is low and is similar to that found in Ibadan, Nigeria.
Measurement of Gastrin and Transforming Growth Factor α Messenger RNA Levels in Colonic Carcinoma Cell Lines by Quantitative Polymerase Chain Reaction
Authors: Graham S. Baldwin, Qun-Xing Zhang
Journal: Cancer Research (1992)

A synthetic DNA template has been constructed that is suitable for the quantitation of mRNAs encoding gastrin, transforming growth factor α (TGFα), cholecystokinin, and the 78-kDa gastrin-binding protein. The template was used to measure levels of gastrin and TGFα mRNA in 7 colonic and 2 gastric carcinoma cell lines by the polymerase chain reaction. All lines produced detectable gastrin and TGFα mRNA with amounts varying between 2.1 and 540 molecules of gastrin mRNA/103 cells and 1.1 and 28 molecules of TGFα mRNA/103 cells. These results are consistent with the hypothesis that both gastrin and TGFα act as autocrine growth factors in colon carcinoma cell lines.
Endoplasmic Reticulum Ca <sup>2+</sup> Depletion Unmasks a Caffeine-Induced Ca <sup>2+</sup> Influx in Human Aortic Endothelial Cells
Authors: Stefano Corda, Harold A. Spurgeon, Edward G. Lakatta, Maurizio C. Capogrossi, Roy C. Ziegelstein
Journal: Circulation Research (1995)

Abstract Intracellular Ca 2+ pools contribute to changes in cytosolic [Ca 2+ ] ([Ca 2+ ] i ), which play an important role in endothelial cell signaling. Recently, endothelial ryanodine-sensitive Ca 2+ stores were shown to regulate agonist-sensitive intracellular Ca 2+ pools. Since caffeine binds the ryanodine Ca 2+ release channel on the endoplasmic reticulum in a variety of cell types, we examined the effect of caffeine on [Ca 2+ ] i in human aortic endothelial cell monolayers loaded with the fluorescent probe indo 1. Under baseline conditions, 10 mmol/L caffeine induced a small increase in [Ca 2+ ] i from 86±10 to 115±17 nmol/L (mean±SEM); this effect was similar to that of 5 μmol/L ryanodine and was unaffected by buffer Ca 2+ removal. After depletion of an intracellular Ca 2+ store by the irreversible endoplasmic reticulum Ca 2+ -ATPase inhibitor thapsigargin (1 μmol/L), ryanodine did not affect [Ca 2+ ] i . In contrast, caffeine induced a large rapid increase in [Ca 2+ ] i (176±19 to 338±35 nmol/L, P &lt;.001) after thapsigargin exposure; this effect of caffeine was only observed when extracellular Ca 2+ was present. A similar increase in [Ca 2+ ] i was induced by caffeine after depletion of ryanodine- and histamine-sensitive Ca 2+ stores or after pretreatment with the endoplasmic reticulum Ca 2+ -ATPase inhibitor cyclopiazonic acid (10 μmol/L). Thus, under baseline conditions the effect of caffeine on [Ca 2+ ] i is similar to that of ryanodine and appears to be due to the release of an intracellular store. However, after depletion of an endoplasmic reticulum Ca 2+ store, caffeine, but not ryanodine, stimulates Ca 2+ influx, resulting in a large increase in [Ca 2+ ] i . The data suggest that caffeine-induced Ca 2+ influx is controlled by the status of Ca 2+ loading of intracellular Ca 2+ stores in human aortic endothelial cells.
Ovarian Carcinoma In Situ With Germline BRCA1 Mutation and Loss of Heterozygosity at BRCA1 and TP53
Authors: B. A. Werness
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: The two-hit hypothesis for the genesis of cancer predicts that cancer can develop when the wild-type allele of a tumor suppressor gene is lost in an individual with a germline mutation in that gene. Neither loss of heterozygosity (LOH) for BRCA1 nor mutations of the TP53 (also known as p53) gene have been documented prior to invasion in ovarian cancers arising in women with germline BRCA1 mutations. Such documentation is difficult because lesions are rarely identified in ovarian epithelium. We, therefore, looked for LOH at microsatellite polymorphisms linked to the BRCA1 and TP53 tumor suppressor loci in an incidental carcinoma in situ of the ovary removed prophylactically from a woman with a germline BRCA1 mutation. Methods: By use of laser-capture microdissection, we obtained pure populations of atypical ovarian epithelial cells and normal stromal cells. DNA was extracted, amplified with primers flanking polymorphic microsatellites linked to BRCA1 (D17S855 and D17S579) and TP53 (TP53 and D17S786), and analyzed for LOH at these microsatellites. We also tested for p53 expression in the abnormal epithelium by immunohistochemistry. Results: Both of the markers linked to TP53 showed LOH, as did an intragenic BRCA1-linked marker (D17S855). The other microsatellite marker for BRCA1 was uninformative. Immunohistochemical staining with an antibody to p53 showed strong immunoreactivity confined to the atypical epithelium. Conclusions: BRCA1, as well as TP53, can undergo LOH prior to stromal invasion in BRCA1-associated ovarian cancer. Strong immunoreactivity for p53 suggests the presence of mutated p53 in these cells as well. These findings suggest that loss of function of these two tumor suppressor genes occurs early in ovarian carcinogenesis in BRCA1 mutation carriers.
Erosions or not in GORD? The potential role of oesophageal cell proliferation
Authors: C Calabrese
Journal: Gut (2005)

Gastro-oesophageal reflux is an almost universal daily occurrence, but only a small percentage of the population develops gastro-oesophageal reflux disease (GORD) and, among them, a small number develop erosive oesophagitis (ERD) or one of its complications.1,2 It is well accepted that the pathophysiology of GORD is related to failure of antireflux mechanisms but several phenomena are not fully explained on the basis of this sequence.3 There is no apparent relation between damage and the amount and quality of refluxate.4 It is not known why the same amount of refluxate determines GORD in one patient and not in another.2 It is also unclear whether there is a relation between these unexplained questions and the possible influence of proliferative responses of epithelial proliferating cells to damage. Hence we evaluated cell proliferation of the oesophageal epithelium using Ki67 immunostaining in normal subjects and in patients with GORD, with or without erosions.

Patients gave written informed …
Pericarditis due to Bacteroides melaninogenicus secondary to a teratoma.
Authors: T R Rasmussen, J S Sorensen
Journal: Thorax (1988)

Over the past 50 years the aetiology of purulent pericarditis has changed.Most cases used to be caused by Gram positive bacteria, but now there is a higher incidence of cases due to Gram negative bacteria and fungi.'Anaerobes are rarely found.'In the following case Bacteroides melaninogenicus, an anaerobic Gram negative bacillus, caused a purulent pericarditis secondary to a perforating teratoma.Case report
Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort
Authors: Ascanio Tridente, Geraldine M. Clarke, A. Walden, S. McKechnie, P. Hutton, G. H. Mills, A. C. Gordon, P. A. H. Holloway, J.-D. Chiche, J. Bion, F. Stuber, C. Garrard, C. J. Hinds
Journal: Intensive Care Medicine (2013)
Phase II study of bleomycin, vindesine, mitomycin C and cisplatin (BEMP) in recurrent or disseminated squamous cell carcinoma of the uterine cervix
Authors: I.F. van Luijk, C. Coens, M.E.L. van der Burg, A. Kobierska, M. Namer, C. Lhomme, P. Zola, G. Zanetta, J.B. Vermorken
Journal: Annals of Oncology (2006)
Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms
Authors: G. Matthew Longo, Wanfen Xiong, Timothy C. Greiner, Yong Zhao, Nicola Fiotti, B. Timothy Baxter
Journal: Journal of Clinical Investigation (2002)

Matrix metalloproteinases (MMPs) 9 and 2 are increased in human abdominal aortic aneurysm (AAA) tissue, but their precise role and potential interaction remain unclear. Experimental induction of aortic aneurysms in mice genetically deficient in these peptidases could provide new insight into AAA pathogenesis. Mice deficient in the expression of MMP-9 (MMP-9KO) or MMP-2 (MMP-2KO) and their corresponding wild-type background mice (WT) underwent AAA induction by abluminal application of calcium chloride (CaCl2). No aneurysm formation was observed at 10 weeks after treatment in either the MMP-9KO or the MMP-2KO mice, whereas the corresponding WT mice showed an average 74% and 52% increase in aortic diameter, respectively. Reinfusion of competent macrophages from the corresponding WT strains into knockout mice resulted in reconstitution of AAA in MMP-9KO but not MMP-2KO mice. These findings suggest that macrophage-derived MMP-9 and mesenchymal cell MMP-2 are both required and work in concert to produce AAA.