tbuckley/cabot-search huggingface dataset:
Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces
Authors: R. Farre, R. De Vos, K. Geboes, K. Verbecke, P. V. Berghe, I. Depoortere, K. Blondeau, J. Tack, D. Sifrim
Journal: Gut (2007)

In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces.Male Sprague-Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to (51)Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy.Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8+/-7.1 pmol/cm(2) vs 5.8+/-2.1 pmol/cm(2)) (p<0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin).Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.
Changes in CD11b and L-selectin Expression on Eosinophils Are Mediated by Human Lung Fibroblasts<i>In Vitro</i>
Authors: FOKJE M. SPOELSTRA, HESSEL HOVENGA, JACOBIEN A. NOORDHOEK, DIRKJE S. POSTMA, HENK F. KAUFFMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Eosinophilic airway infiltration is a central feature in asthma. Eosinophils recovered from bronchoalveolar fluid show an activated phenotype, e.g., increased CD11b and decreased L-selectin expression. We investigated whether lung fibroblasts are able to activate eosinophils in vitro, and if so, which activating factor is most important. CD11b and L-selectin expression of isolated peripheral blood eosinophils were measured by flow cytometry after coculture with normal lung fibroblasts or their conditioned medium. We found that eosinophil CD11b expression increased (154% and 210%, p < 0.05) and L-selectin expression decreased (59% and 35.5%, p < 0.05) on eosinophils compared with baseline (100%) after 4 and 24 h of coculture with interleukin-1-beta (IL-1 β )–stimulated fibroblasts, respectively. Conditioned medium of stimulated fibroblasts also increased CD11b expression, but to a smaller extent (p < 0.05). L-selectin expression of eosinophils in cocultures was not different from that of eosinophils in conditioned medium. Only anti–granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) reduced the activation of eosinophils in conditioned medium to almost basal levels (p < 0.05). An increase in CD11b expression is mediated by cytokines as well as direct cell contact, whereas a decrease in L-selectin expression is only mediated by cytokines. GM-CSF released by fibroblasts is an important factor in the modulation of both CD11b and L-selectin expression. These results show that lung fibroblasts can activate eosinophils by both adhesive interactions and by soluble factors.
Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia.
Authors: E R Swenson, H T Robertson, M P Hlastala
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We studied the effect of low concentrations (2 to 4%) of inspired CO2 on gas exchange and ventilation-perfusion (VA/Q) relationships in healthy normocapnic anesthetized dogs during constant mechanical ventilation by the multiple inert gas elimination technique (MIGET). One group was studied at normal tidal volumes (12 to 14 ml/kg) and rates (13 to 15/min) in normoxia, and the other in mild hyperoxia (FIO2 = 0.50) and hypoxia (FIO2 = 0.15). In normoxic dogs there were progressive increases in arterial PO2 and reductions in the alveolar-to-arterial PO2 and arterial-to-mixed expired PCO2 differences in response to increases in FICO2. This increased gas exchange efficiency was characterized by reductions in both dead space ventilation and VA/Q mismatch. Better VA/Q matching was characterized by reduction in the log standard deviation of ventilation (log SDV) without significant change in the log standard deviation of perfusion (log SDQ). Gas exchange parameters returned to baseline when dogs were returned to CO2-free inspired gas. In the second group, the effects of 3% inspired CO2 were of comparable magnitude in both mild hypoxia and hyperoxia. In this group (taking hyperoxic values as baseline), there were improved gas exchange and less VA/Q heterogeneity with inspired hypoxia, both with and without inspired CO2. In contrast to the effects of added inspired CO2, improved VA/Q matching with hypoxia was characterized by reductions in both log SDV and log SDQ.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 14461: Versican Facilitates the Differentiation and Migration of Endothelial Progenitor Cells in Yolk Sac for Vasculogenesis
Authors: Nishant Mittal, Sung H Yun, Hirokazu Enomoto, Takami Yamamoto, Atsusi Kawakami, Akira Kudo, Misato Fujita, Atsushi Shimizu, Yoshihiko Saito, Osamu Nakagawa, Shinji Makino, Keiichi Fukuda
Journal: Circulation (2013)

Background: During embryogenesis, endothelial progenitor cells (EPCs) of blood islands develop migratory phenotype and directed to form anterior choroid plexus, thus initiates vasculogenesis. One o...
Observations on OCCUPATIONAL DERMATITIS
Authors: W. G. Harvey
Journal: BMJ (1933)

bservations| ahrything 'Whih in excess, or under special circumstances, O may not give rise to skin lesions.It may not be easy to ON assess how far such an agent is merely actuating or is OCCUPATIONAL DERMATITIS * to be held fully responsible.Thus, sunlight, for all its health-giving properties, may produce an acute dermatitis BY if exhibited in excess to a healthy skin; it may also W. G. HARVEY, M
The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension
Authors: N. Nickel, H. Golpon, M. Greer, L. Knudsen, K. Olsson, V. Westerkamp, T. Welte, M.M. Hoeper
Journal: European Respiratory Journal (2011)

Current guidelines for the treatment of patients with idiopathic pulmonary arterial hypertension (IPAH) recommend basing therapeutic decision-making on haemodynamic, functional and biochemical variables. Most of these parameters have been evaluated as risk predictors at the time of diagnosis. The aim of the present study was to assess the prognostic impact of changes in these parameters after initiation of targeted therapy. A cohort of 109 patients with IPAH who had undergone haemodynamic, functional and biochemical assessments at baseline and 3-12 months after initiation of pulmonary arterial hypertension (PAH)-targeted therapy, were followed for a median 38 months in order to determine predictors of mortality at baseline and during the course of their disease. Within the observation period, 53 (48.6%) patients died and four (3.7%) underwent lung transplantation. Kaplan-Meier estimates for transplantation-free survival were 92%, 67%, and 51% at 1, 3, and 5 yrs, respectively. Among baseline variables, 6-min walk distance, right atrial pressure, cardiac index, mixed-venous oxygen saturation (S(v,O(2))) and N-terminal-pro brain natriuretic peptide (NT-proBNP) were independent predictors of survival. During follow-up, changes in World Health Organization functional class, cardiac index, S(v,O(2)) and NT-proBNP proved significant predictors of outcome. When assigned to prognostic groups, improvements as well as deteriorations in these parameters after initiation of PAH-targeted therapy had a strong impact on survival. Measurements obtained at follow-up had a higher predictive value than variables obtained at baseline. Changes in established predictors of outcome during the course of the disease provide important prognostic information in patients with IPAH.
Changes in exposure of adult non-smokers to secondhand smoke after implementation of smoke-free legislation in Scotland: national cross sectional survey
Authors: Sally J Haw, Laurence Gruer
Journal: BMJ (2007)

<b>Objective</b> To measure change in adult non-smokers9 exposure to secondhand smoke in public and private places after smoke-free legislation was implemented in Scotland. <b>Design</b> Repeat cross sectional survey. <b>Setting</b> Scotland. <b>Participants</b> Scottish adults, aged 18 to 74 years, recruited and interviewed in their homes. <b>Intervention</b> Comprehensive smoke-free legislation that prohibits smoking in virtually all enclosed public places and workplaces, including bars, restaurants, and cafes. <b>Outcome measures</b> Salivary cotinine, self reported exposure to smoke in public and private places, and self reported smoking restriction in homes and in cars. <b>Results</b> Overall, geometric mean cotinine concentrations in adult non-smokers fell by 39% (95% confidence interval 29% to 47%), from 0.43 ng/ml at baseline to 0.26 ng/ml after legislation (P&lt;0.001). In non-smokers from non-smoking households, geometric mean cotinine concentrations fell by 49% (40% to 56%), from 0.35 ng/ml to 0.18 ng/ml (P&lt;0.001). The 16% fall in cotinine concentrations in non-smokers from smoking households was not statistically significant. Reduction in exposure to secondhand smoke was associated with a reduction after legislation in reported exposure to secondhand smoke in public places (pubs, other workplaces, and public transport) but not in homes and cars. We found no evidence of displacement of smoking from public places into the home. <b>Conclusions</b> Implementation of Scotland9s smoke-free legislation has been accompanied within one year by a large reduction in exposure to secondhand smoke, which has been greatest in non-smokers living in non-smoking households. Non-smokers living in smoking households continue to have high levels of exposure to secondhand smoke.
Detection of protein C activation in humans.
Authors: K A Bauer, B L Kass, D L Beeler, R D Rosenberg
Journal: Journal of Clinical Investigation (1984)

We have developed a radioimmunoassay (RIA) for the dodecapeptide that is liberated from protein C when this zymogen is activated by thrombin bound to thrombomodulin present on the vascular endothelium. The protein C activation peptide (PCP) was synthesized using the solid-phase method of Merrifield. Antisera were raised in rabbits to the synthetic analogue coupled to bovine serum albumin with glutaraldehyde. The antibody population obtained was used together with a 125I-labeled tyrosinated ligand and various concentrations of unlabeled PCP to construct a double antibody RIA capable of measuring as little as 10 pM of this component. We have established that the synthetic dodecapeptide has the same immunoreactivity as the native peptide and that the reactivity of protein C is less than 1/2,000 that of PCP on a molar basis. The extremely low levels of peptide in normal individuals as well as the nonspecific contributions of plasma constituents to the immunoreactive signal, necessitated the development of a procedure by which the PCP could be reproducibly extracted from plasma and concentrated approximately 20-fold. This methodology permitted us to demonstrate that the plasma PCP levels in 17 normal donors averaged 6.47 pM, and that elevations up to 180 pM were observed in individuals with evidence of disseminated intravascular coagulation. The validity of these measurements of protein C activation is supported by the fact that, in both of these situations, the RIA signal migrates on reverse-phase high pressure liquid chromatography in a manner identical to that of the native dodecapeptide. We have also noted that the mean PCP concentration in seven patients fully anticoagulated with warfarin averaged 2.61 pM. Our studies also show that PCP is cleared from the plasma of primates with a t1/2 of approximately 5 min. Given that the t1/2 of activated protein C is estimated to be 10-15 min, the latter enzyme appears to exert its effects on the activated cofactors of the coagulation system at concentrations considerably less than 1.0 nM.
The X-Linked Intellectual Disability Protein PHF6 Associates with the PAF1 Complex and Regulates Neuronal Migration in the Mammalian Brain
Authors: Chi Zhang, Luis A. Mejia, Ju Huang, Pamela Valnegri, Eric J. Bennett, Julius Anckar, Arezu Jahani-Asl, Gilbert Gallardo, Yoshiho Ikeuchi, Tomoko Yamada, Michael Rudnicki, J. Wade Harper, Azad Bonni
Journal: Neuron (2013)
An Unusual Case of Congenitally Corrected Transposition of the Great Arteries in the Elderly
Authors: Caterina Milici, Daniella Bovelli, Daniele Forlani, Carlo Bock, Dario Formigli, Georgette Khoury, Valentino Borghetti, Stefano Nardi, Marcello Dominici, Gerardo Rasetti, Alessandro Pardini
Journal: Circulation (2008)
Association of Maternal Diabetes Mellitus in Pregnancy With Offspring Adiposity Into Early Adulthood
Authors: Debbie A. Lawlor, Paul Lichtenstein, Niklas Långström
Journal: Circulation (2011)

Background— Maternal diabetes mellitus in pregnancy results in greater offspring adiposity at birth. It is unclear whether it is associated with greater adiposity into adulthood, and if so, whether this is via intrauterine mechanisms or shared familial characteristics. Methods and Results— A record-linkage prospective cohort study of 280 866 singleton-born Swedish men from 248 293 families was used to explore the intrauterine effect of maternal diabetes mellitus on offspring body mass index (BMI) in early adulthood. Maternal diabetes mellitus during pregnancy was associated with greater mean BMI at age 18 in their sons. The difference in BMI was similar within brothers and between nonsiblings. BMI of men whose mothers had diabetes mellitus during their pregnancy was on average 0.94 kg/m 2 greater (95% confidence interval [CI], 0.35 to 1.52) than in their brothers born before their mother was diagnosed with diabetes, after adjustment for birth year, maternal age, parity and education, birth weight, gestational age, and age at assessment of BMI. Early-pregnancy BMI was positively associated with son's BMI between nonsiblings, but there was no association within brothers. Adjustment of the maternal diabetes–offspring BMI association for maternal BMI did not alter the association either within brothers or between nonsiblings. Results were also robust to sensitivity analyses restricting the within-sibling analyses to siblings born within 3 years of each other. Conclusion— Maternal diabetes mellitus has long-term consequences for greater BMI in offspring; this association is likely to be via intrauterine mechanisms, and is independent of maternal BMI in early pregnancy.
Extraskeletal Ewing's sarcoma: results of combined modality treatment.
Authors: T J Kinsella, T J Triche, P S Dickman, J Costa, J E Tepper, D Glaubiger
Journal: Journal of Clinical Oncology (1983)

Eleven patients with extraskeletal Ewing's sarcoma (EES) were treated with combined modality therapy at the National Cancer Institute. The diagnosis of EES was reserved for lesions that were identical to Ewing's sarcoma of bone by light and electron microscopy. Diagnostic work-up to rule out a skeletal primary included bone scan, localized views of adjacent bone, and bone tomography. Seven patients presented with an extremity primary and four patients had a truncal primary. No patients had evidence of metastases at presentation. Patients were treated with combined modality therapy consisting of high-dose local irradiation and vincristine, actinomycin D, and cyclophosphamide chemotherapy following a biopsy or local excision. No attempt was made to excise widely the primary tumor mass. Gross tumors generally responded rapidly to the combined modality treatment. Of 11 patients, seven (64%) remain disease free, with a follow-up of three to seven years from completion of therapy. Long-term local control was established in nine of 11 patients (82%). Autopsy findings on two patients with local failure showed no tumor involvement of adjacent bone. Attempts at gross resections by radical surgical procedures do not routinely appear to be necessary in light of the high local control rates with high-dose irradiation.
Transcolonic ventral wall hernia mesh fixation in a porcine model
Authors: D. Fong, M. Ryou, R. Pai, A. Tavakkolizadeh, D. Rattner, C. Thompson
Journal: Endoscopy (2007)

See also: Commentaire des travaux de D. G. Fong et al. pp. 865 et M. Ryou et al. pp. 881Endoscopy 2007; 39(10): 933-935DOI: 10.1055/s-0032-1308877
Cyclopentenone Prostaglandins Inhibit Cytokine-Induced NF-κB Activation and Chemokine Production by Human Mesangial Cells
Authors: BRAD H. ROVIN, LING LU, ANNA COSIO
Journal: Journal of the American Society of Nephrology (2001)

Abstract. In the kidney an uncontrolled inflammatory response to an acute insult may lead to chronic inflammation, permanent tissue damage, and progressive renal insufficiency. Resolution of acute inflammation likely is dependent on endogenous regulatory mechanisms activated in parallel with mediators of renal inflammation. These mechanisms are postulated to attenuate the renal expression of proinflammatory cytokines, including the chemokines responsible for recruiting leukocytes to the kidney, thus facilitating the transition from inflammation to healing. To understand the regulation of the inflammatory response within the kidney, the effects of anti-inflammatory J series cyclopentenone prostaglandins on chemokine production by human mesangial cells were examined. Treatment of mesangial cells with prostaglandin J 2 and 15-deoxy-Δ 12,14 -prostaglandin J 2 blocked interleukin-1β—induced monocyte chemoattractant protein-1 mRNA expression and protein production. This correlated with failure of the transcription factor nuclear factor-κB (NF-κB) to translocate to the nucleus and bind to its recognition motif, a step required for cytokine-induced monocyte chemoattractant protein-1 gene activation. NF-κB failed to translocate because the cyclopentenone prostaglandins attenuated degradation of the NF-κB inhibitor IκB-α. These data suggest that certain prostaglandins can limit the extent of renal chemokine expression and thus may have an important role in resolving renal inflammation.
Disruption of the NF-κB/IκBα Autoinhibitory Loop Improves Cognitive Performance and Promotes Hyperexcitability of Hippocampal Neurons
Authors: David J Shim, Li Yang, J Graham Reed, Jeffrey L Noebels, Paul J Chiao, Hui Zheng
Journal: Molecular Neurodegeneration (2011)

Abstract Background Though originally discovered in the immune system as an important mediator of inflammation, NF-κB has recently been shown to play key roles in the central nervous system, such as synaptogenesis, synaptic plasticity, and cognition. NF-κB activity is normally tightly regulated by its primary inhibitor, IκBα, through a unique autoinhibitory loop. In this study, we tested the hypothesis that the IκBα autoinhibitory loop ensures optimal levels of NF-κB activity to promote proper brain development and function. To do so, we utilized knock-in mice which possess mutations in the IκBα promoter to disrupt the autoinhibitory loop (IκBα M/M KI mice). Results Here, we show that these mutations delay IκBα resynthesis and enhance NF-κB activation in neurons following acute activating stimuli. This leads to improved cognitive ability on tests of hippocampal-dependent learning and memory but no change in hippocampal synaptic plasticity. Instead, hippocampal neurons from IκBα M/M KI mice form more excitatory and less inhibitory synapses in dissociated cultures and are hyperexcitable. This leads to increased burst firing of action potentials and the development of abnormal hypersynchronous discharges in vivo . Conclusions These results demonstrate that the IκBα autoinhibitory loop is critical for titrating appropriate levels of endogenous NF-κB activity to maintain proper neuronal function.
The womb and lung function later in life
Authors: E.J.L.E. Vrijlandt, J. Gerritsen
Journal: European Respiratory Journal (2004)

<b>Introduction:</b> The objective of this study is to evaluate how prevalent inhaler misuse is in elderly patients with respiratory disease, in a real-world setting. Also, we compared the differences between inhaler devices with respect to misuse and error correction. <b>Methods:</b> Participants were eligible if they were aged ≥65 years, using inhaler for at least 3 months, and received inhaler training previously. Patients were assessed for inhaler technique using standardized checklists at first and 90 day follow-up visit. We compared six different types of inhalers. The primary outcome was the differences of adequate use ratio between inhaler devices. Secondary outcomes included comparison of error correction after training, patient satisfaction on each device and most common step of misuse. <b>Results:</b> A total of 230 patients (mean age 76.08±6.04, male 93.5%) were included in the study. Despite being educated in the past, appropriate usage ratio was low and pMDI was the lowest (37.1% for pMDI, 56.3% for soft mist inhaler and 51.6% for DPI, respectively; p=0.078). Among DPI, there is significant difference between inhaler device types (62.8% for Turbuhaler, 30.0% Diskus, 63.1% Ellipta and 38.4% Breezhaler and Handihaler, respectively; p=0.006). After face-to-face training, appropriate usage ratio increased and there was no significant difference between inhaler device types (72.2% for Evohaler, 100% Respimat, 71.4% Turbuhaler, 76.0% Ellipta and 58.5% Breezhaler and Handihaler, respectively;p=0.178). <b>Conclusion:</b> New inhalers were developed, but the accuracy of inhaler use was still low. This study results suggest that repeat training is more important than inhaler type.
Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial
Authors: Alessandro Rambaldi, Anna Grassi, Arianna Masciulli, Cristina Boschini, Maria Caterina Micò, Alessandro Busca, Benedetto Bruno, Irene Cavattoni, Stella Santarone, Roberto Raimondi, Mauro Montanari, Giuseppe Milone, Patrizia Chiusolo, Domenico Pastore, Stefano Guidi, Francesca Patriarca, Antonio M Risitano, Giorgia Saporiti, Massimo Pini, Elisabetta Terruzzi, William Arcese, Giuseppe Marotta, Angelo Michele Carella, Arnon Nagler, Domenico Russo, Paolo Corradini, Emilio Paolo Alessandrino, Giovanni Fernando Torelli, Rosanna Scimè, Nicola Mordini, Elena Oldani, Rosa Maria Marfisi, Andrea Bacigalupo, Alberto Bosi
Journal: The Lancet Oncology (2015)