tbuckley/cabot-search huggingface dataset:
Fungal colonization of oxygen humidifier and nebulizer chambers
Authors: Tushar Sahasrabudhe, Savita Jadhav, Vipul Kalley, Nageswari Gandham
Journal: European Respiratory Journal (2011)

Humidified oxygen and nebulizers are routinely used in hospitalized patients suffering from respiratory ailments. These can however be potential source of allergens or infection if colonized by fungi. We undertook a study to determine if the oxygen humidifier chambers of portable cylinders and central lines at our hospital were colonized by fungi. The Hudson9s chambers of nebulizers were also studied as they remain wet after use. Samples of these were obtained using sterile swabs on Tuesday as these chambers are usually cleaned on every Saturday. Spot samples were taken from ICUs, wards, casualty and OPD on a single day. Air samples were also obtained on the same day to determine if the fungal spore load in the inhaled room air was normal or high. 46/53 (86.79%) swabs form oxygen humidifiers and 7/17 (41.17%) swabs from Hudson9s chambers grew fungi. There were a total of 14 species of fungi identified altogether. 4 of them are virulent strains and 6 are known allergens for asthmatics. The colonization was less in shallow Hudson9s chambers (35.71%) as compared to the reusable long ones (66.66%). The air samples showed insignificant growth. The study indicates a potential in-hospital source of allergens and infection. The oxygen and nebulizer chambers need to be cleaned more frequently with disinfectants.
Suppressive effect of a mint aqueous extract on IL-13 production
Authors: Fatemeh Hajighasemi
Journal: European Respiratory Journal (2011)

Background:  Medicinal plants have been broadly used in treatment of various diseases. Mints are a group of plants belonging to labiatae family have anti-bacterial, anti-tumoral and anti-inflammatory effects. Peppermint is a mint specious extensively used in therapy of several disorders such as common cold and bronchitis. The anti-bronchospasmodic and anti-allergic effects of peppermint have also been shown. Elevation of interleukin-13 (IL-13) (a Th2- type cytokine) level is a well known indicator of allergy. In the present study the effect of aqueous extract of peppermint on IL-13 production in human peripheral blood mononuclear cells (hPBMCs) has been assessed in vitro.   Methods:  The hPBMCs were isolated from the venous blood of healthy volunteers by ficoll-hypaque-gradiant centrifugation. Then the PBMCs were cultured in complete RPMI medium. The cells at logarithmic growth phase, were incubated with different concentrations of aqueous extract of peppermint leaves (0.01-10 mg/ml) in triplicate for 24 hours. Afterward the cell culture supernates were collected and the IL-13 concentration was measured using a standard ELISA kit.   Results:  Peppermint aqueous extract significantly decreased the IL-13 production in hPBMCs dose-dependently.   Conclusions:  The results of this study indicate that peppermint aqueous extract down-regulates the production of IL-13 in hPBMCs. Regarding the important role of IL-13 in atopic allergy, the anti-allergic activity of peppermint and also its inhibitory effect on bronchospasm (a symptom of respiratory allergy), may be partly due to its inhibitory effects on IL-13 production.
T3 Severe hypoxia exists within pulmonary tuberculosis lesions and augments matrix metalloproteinase-mediated immunopathology
Authors: M Belton, S Brilha, T Fryer, Y Hong, F Mauri, N Patel, L Tezera, K Nijran, PT Elkington, JS Friedland
Journal: Thorax (2013)

<h3>Introduction</h3> Mycobacterium tuberculosis (MTb) causes approximately two million deaths each year. Extensive lung destruction is a hallmark of pulmonary tuberculosis and is caused by the breakdown of lung extracellular matrix by host matrix metalloproteinases (MMPs). Hypoxia upregulates gene expression and secretion of many inflammatory mediators via hypoxia-inducible factor (HIF-1α). Hypoxia has been demonstrated in several animal models of TB infection but no studies have been performed to investigate hypoxia in humans. <h3>Methods</h3> To investigate the presence of hypoxia in human <i>M.tb</i> infection we performed PET-CT scanning using the hypoxia tracer [18F]FMISO in patients with pulmonary infection. Next, primary human monocyte-derived macrophages (MDMs) and human respiratory epithelial cells were stimulated by <i>M.tb</i> H37RV or conditioned media from Mtb-infected monocytes (CoMTb) in a specially commissioned hypoxia workstation at 1% O2, 5% CO2. MMPs and their specific inhibitors (TIMP-1/2) were analysed by ELISA, Luminex array, zymography and confocal microscopy. Gene expression was analysed by qPCR and promoter activity by dual luciferase activity. Total HIF-1α was measured by western analysis. The effect of HIF-1α blockade was investigated using HIF-1a siRNA. <h3>Results</h3> PET-CT scans demonstrated evidence of tracer trapping in regions of consolidation and in regions surrounding pulmonary cavities indicating severe hypoxia. Hypoxia potently upregulated MMP-1 in <i>M.tb</i>-stimulated primary MDMs and MMP-1 and MMP-9 in respiratory epithelial cells compared to normoxia (p &lt; 0.001). Similarly, hypoxia increased MMP-1 gene expression -2500 fold and potently increased MMP-1 promoter activity (p &lt; 0.001). Site-directed mutagenesis of the NFκB binding site in the MMP-1 promoter and SC514 and helenalin chemical inhibition demonstrated that increased MMP-1 activity in hypoxia was regulated via an NFκB dependent mechanism. <i>M.tb</i> infection caused stabilisation of HIF-1α protein even under conditions of normoxia but was more pronounced in hypoxia. Immunohistochemistry of patient samples demonstrated strong HIF-1α immunoreactivity in tuberculosis patients compared to controls. HIF-1α siRNA confirmed that increased MMP-1 activity in hypoxia occurred by a HIF-1α-dependent mechanism. <h3>Conclusion</h3> We demonstrate for the first time that severe hypoxia develops within pulmonary TB lesions. Hypoxia increases <i>M.tb</i>-driven MMP-1/9 gene expression and secretion in a HIF-1a-dependent manner. These results support the hypothesis that during Tb infection, hypoxia develops and promotes immunopathology.
Estrogen Effects on Sister Chromatid Exchanges in Mouse Uterine Cervical and Kidney Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: K Hillbertz-Nilsson, J G Forsberg
Journal: JNCI Journal of the National Cancer Institute (1985)

Uterine cervical fibroblasts and kidney cells from 3-to 4-day-old, previously untreated or phenobarbital [(PBA) CAS: 50-06-6]-treated female NMRI mice were cultured in vitro in the presence of diethylstilbestrol [(DES) CAS: 56-53-1] or 17β-estradiol [(E2) CAS: 50-28-2]. DES at 10−7M in the culture medium increased the number of sister chromatid exchanges (SCE); no further increase was obtained with higher concentrations of DES. Pretreatment of the females with PBA resulted in an increase in SCE when DES was used in the range of 10−7 to 10−5M. The level of this increase was significantly higher than that in fibroblasts from untreated females. E2 had no effect. DES had no effect on SCE in kidney cells from PBA-treated females. Indomethacin and α-naphthoflavone reduced the number of SCE in PBA-exposed fibroblasts to an intermediate level. The presence of both enzyme inhibitors in the medium depressed the number of SCE to the control level.
Randomized, placebo-controlled study of asthmatic smokers treated with montelukast or mid-dose fluticasone
Authors: David Price, Todor Popov, Leif Bjermer, Susan Lu, Romana Petrovic, Anish Mehta, Jolanta Strus, Polos Peter, George Philip
Journal: European Respiratory Journal (2011)

Background:  Previous data suggest smoking reduces therapeutic effectiveness in asthma, particularly for corticosteroids (CS) ( Lazarus et al. AJRCCM. 2007;175:783-90 ). This study evaluates montelukast (Mont) 10mg daily and fluticasone propionate (FP) 250μg bid, each compared with placebo (Pbo), in patients with self-reported active smoking (after previous inability to quit) and asthma.   Methods:  Patients (ages 18-55 years, with asthma [≥1 year], FEV 1  60%-90%predicted, airway reversibility [≥12%], and active smoking [≥0.5 to ≤2 packs/day]) were randomized (after a 3-week, single-blind, placebo run-in) to 1 of 3 parallel, 6-month, double-blind treatment arms. Primary efficacy endpoint was Percent of days with Asthma Control (%days-AC) during treatment; AC was defined as a composite: β-agonist (SABA) ≤2 puffs/day, no nighttime symptoms (N-Sxs), and no unscheduled healthcare (U-Hc) or systemic-CS use. Adverse events (AEs) were also evaluated.   Results:  The%days-AC over 6 months of treatment was 45% (Mont [N=347]), 49% (FP [N=336]) and 39% (Pbo [N=336]); p-values for Mont and FP (each vs Pbo) were p   Conclusion:  In a population of asthmatic patients actively smoking cigarettes, both montelukast 10mg daily and fluticasone 250μg bid significantly increased the percent of days with asthma control, compared with placebo.
The use of lambs chests in chest drain insertion simulation
Authors: Alasdair Nazerali-Maitland, Mitchell Goldenberg, Nadim Jiwa
Journal: European Respiratory Journal (2011)

In an attempt to familiarize medical trainees with chest drain insertion, we sought to find a successful way of instructing students with its insertion technique.  Students were given a thirty-minute lecture on chest anatomy, indications for insertion and then the insertion was demonstrated. Students were then taught the Seldinger (tube over guide-wire) technique and also the surgical drain (directly-visualized) insertion technique in a one-hour lab session. No direct comparison was made between other popular simulation mediums (such as plastic models or pork back ribs) nor then were students subsequently directly observed inserting tubes on actual patients.  The students were instructed then monitored and scored on successful insertion in the pleural space by an examiner informally. In discussion it was felt that the tactile feedback from the lamb9s carcasses demonstrated outstanding anatomical correlation and also demonstrated similar difficulties to human chest drain insertion. Both the anterior & mid-axillary lines were clearly visualized as well as the costal margins. There was also the opportunity to demonstrate administration of local anaesthetic agents as well as one of the most common pitfalls of chest tube insertion: hitting the bone. The session was received very well with feedback revealing an appropriate amount of time spent on both instruction and demonstration.  Lamb9s thoraces are a superb medium for simulation-based instruction of chest tube insertion. The use of an animal model has its benefits with respect to anatomical realism and the tactile realism of feeling actual muscle and bone. It likely provided a good stepping-stone between abstract classroom insertion instruction and hospital patient insertion.
Investigating the role of prostaglandin D2 in airway sensory nerve firing: Relevance to disease
Authors: Sarah Maher, Mark Birrell, John Adcock, Michael Wortley, Sara Bonvini, Megan Grace, Maria Belvisi
Journal: European Respiratory Journal (2013)

Levels of Prostaglandin D2 (PGD2) are known to be increased in the lungs of patients with respiratory diseases such as asthma and COPD. Indeed, there is intense ongoing research into the inflammatory role of PGD2 and the role of CRTH2 (one of two PGD2 receptors). However, there is little known about the function of PGD2 on airway sensory nerves and cough in these diseases. As excessive coughing is a key symptom of these diseases, the aim of this study is to determine how PGD2, and the two receptors it acts on, impact on airway sensory nerves.

Initial studies showed that inhaled PGD2 caused dose-related coughing in guinea pigs (GP). PGD2 increased the calcium signal in primary GP airway ganglia cells and RT-PCR showed both receptors for PGD2 (DP1 and CRTH2) are expressed. Using pharmacological tools and tissues harvested from human lungs and PGD2 receptor deficient mice, we generated data that showed that PGD2 activates sensory nerves via the DP1 receptor. This was further corroborated in an in vivo single fibre recording preparation.

As we could detect CRTH2 expression in the nerve ganglia, we went on to study whether receptor activation modulated responses to other tussive agents. Interestingly, the data showed that activating CRTH2 inhibited capsaicin (TRPV1 agonist) induced sensory nerve firing in vitro and in vivo .

In conclusion, PGD2 can activate airway sensory nerves via the DP1 receptor and appears to attenuate TRPV1 driven nerve firing via the CRTH2 receptor. This data suggests that the excessive cough observed in respiratory diseases could be due to the higher levels of PGD2.
Combined Effects of Radiation and Methotrexate on the Cells of the Rat Subependymal Plate
Authors: A D Morris, J W Hopewell
Journal: Journal of the Royal Society of Medicine (1983)

The brains of 20-week-old rats were locally irradiated with single doses of X-rays (400–1400 cGy). A similar group of animals received an intraventricular injection of methotrexate (MTX) prior to irradiation with single doses of X-rays (600–1400 cGy). Animals were killed six weeks after irradiation. A group of unirradiated age-matched animals acted as controls. In irradiated animals, the most severe effect on the subependymal plate (SEP) of the brain was denoted by the fall in the mitotic count (MC) and the number of small dark (SD) nucleated cells. SD nucleated cells are believed to represent the proliferative compartment of the subependymal layer. Other cell types in the SEP, believed to arise from the SD nucleated population, were affected to a lesser degree. After combination treatment with MTX, the decline in the MC and the SD nuclear density was more severe. The data for the dose-related decline in SD nuclear density and the MC fitted equally well on log-linear and linear plots. From the log-linear plots of the data it was concluded that MTX was radiation dose modifying (DMF 1.25–1.44). However, on the basis of the linear plots the effect of radiation and MTX was apparently additive. While no firm conclusions could be drawn regarding the mechanism of action of MTX on the radiation response of SEP cells, the possible mechanisms are discussed.
Small-scale gene duplications played a major role in the recent evolution of wheat chromosome 3B
Authors: Natasha M. Glover, Josquin Daron, Lise Pingault, Klaas Vandepoele, Etienne Paux, Catherine Feuillet, Frédéric Choulet
Journal: Genome biology (2015)

Bread wheat is not only an important crop, but its large (17 Gb), highly repetitive, and hexaploid genome makes it a good model to study the organization and evolution of complex genomes. Recently, we produced a high quality reference sequence of wheat chromosome 3B (774 Mb), which provides an excellent opportunity to study the evolutionary dynamics of a large and polyploid genome, specifically the impact of single gene duplications. We find that 27 % of the 3B predicted genes are non-syntenic with the orthologous chromosomes of Brachypodium distachyon, Oryza sativa, and Sorghum bicolor, whereas, by applying the same criteria, non-syntenic genes represent on average only 10 % of the predicted genes in these three model grasses. These non-syntenic genes on 3B have high sequence similarity to at least one other gene in the wheat genome, indicating that hexaploid wheat has undergone massive small-scale interchromosomal gene duplications compared to other grasses. Insertions of non-syntenic genes occurred at a similar rate along the chromosome, but these genes tend to be retained at a higher frequency in the distal, recombinogenic regions. The ratio of non-synonymous to synonymous substitution rates showed a more relaxed selection pressure for non-syntenic genes compared to syntenic genes, and gene ontology analysis indicated that non-syntenic genes may be enriched in functions involved in disease resistance. Our results highlight the major impact of single gene duplications on the wheat gene complement and confirm the accelerated evolution of the Triticeae lineage among grasses.
Innate Immune System Damage in Human Immunodeficiency Virus Type 1 Infection
Authors: SARAH HOWIE, ROBERT RAMAGE, TIM HEWSON
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

HIV infection affects the innate as well as the acquired immune systems. Critically, it changes the function of macrophages, which link the innate and acquired responses through their ability to present antigen to CD4(+) T lymphocytes. Patients with HIV infection have a reduced capacity to deal with subsequent pathogen exposure and many suffer from chronic pulmonary infections. We have produced complex synthetic peptides that mimic the function of viral gp120 and may represent prototypes of molecules that can prevent or ameliorate HIV-induced damage to the immune system.
Community acquired pneumonia: Can physiotherapists and occupational therapists help reduce the length of stay?
Authors: Arun Khanna, Abrar Almulla
Journal: European Respiratory Journal (2012)

Introduction : Community Acquired Pneumonia (CAP) places a significant burden on healthcare budget 1 . With an increasingly ageing population, an unmet need for measures to cut down on length of stay (LOS) from this diagnosis exists.   Methods : We retrospectively analysed all cases of CAP admitted to our hospital for a period of six months. After adjusting for co-morbidities with charlson index, 40 cases of LOS over and above the expected LOS were identified. Their case notes were analysed in detail to identify potential remediable factors to help reduce overall LOS.   Results : All of the 40 cases received timely diagnosis, review by senior clinicians and appropriate treatment in keeping with national guidelines. The average age was 79 years. Higher Charlson index correlated well with increased LOS. Overall, 42% (n=17) developed complications of pneumonia resulting in increased LOS. Out of these, 23% (n=4) continually deteriorated resulting in an overall mortality of 10%. Unmet occupational and physiotherapist needs resulted in an increased LOS in 45% (n=18) after time to clinical stability (TCS).In 10 % (n=4) increased LOS was attributable to ongoing social needs whilst no documented cause could be ascertained in the last remaining case.   Conclusions : Early institution of physiotherapy and occupational therapy interventions can potentially help reduce LOS from CAP and reduce economic burden on healthcare budget. A multi-disciplinary team approach to CAP, especially in elderly patients, should be considered.   Reference   1) Welte T  el al ; Thorax 2012 Jan;67(1):71-9.
Analysis of impulse oscillometry data of chronic obstructive pulmonary diseae patients in community health care center, Ho Chi Minh City, Vietnam
Authors: Xuan Tan Tran, Quang Dang Khoa Truong, Thi Sen Nguyen, Thi Tuyet Lan Le
Journal: European Respiratory Journal (2013)

Background: Impulse oscillometry system is a non-invasive method to access the oscillatory mechanics of the respiratory system. The aim of this study was to analyze the accuracy of the impulse oscillometry parameters in diagnosis of COPD, and investigate which IOS parameters are related to airflow obstruction in COPD patients in Community Health Care Center in Ho Chi Minh City, Vietnam.

Methods: The study contain thirty COPD patients and thirty-two healthy people, whole of them are greater than 40 years, were recruited in Community Health Care Center (CHAC), Ho Chi Minh city, Vietnam. IOS measurements (R5, R20, X5, X20, AX & Fres), and Spirometry (FEV1, FVC) were performed. Pearson or Spearman correlation determined the relationships between IOS and Spirometry.

Results: X5, X20, AX and Fres were all significantly associated (p < 0.05) with FEV1. However, R5 and R20 were not related to FEV1. The strongest associations were observed between FEV1 and the reactance measurements X5 (r = 0.65), and AX (r = -0.61).

Conclusions: IOS reactance measurements are closer related than IOS resistance measurements in COPD patients. The IOS reactance measurements can be a significant value for diagnosis COPD patients.
The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype.
Authors: J Mercieca, E Matutes, C Dearden, K MacLennan, D Catovsky
Journal: Journal of Clinical Oncology (1994)

To assess the results of treatment with the purine analog 2'deoxycoformycin (pentostatin [DCF]) in patients with postthymic T-cell malignancies.One hundred forty-five patients with postthymic T-cell malignancies were given DCF intravenously at 4 mg/m2/wk for the first 4 weeks and then every 2 weeks until maximal response; the last 30 patients received weekly injections until maximal response.The overall response rate was 32% (complete responses [CRs] plus partial responses [PRs]), with marked variation according to diagnosis. The best responses occurred in patients with Sézary syndrome (62%) and T-prolymphocytic leukemia (T-PLL) (45%), with CRs in three of 16 Sézary syndrome and five of 55 T-PLL patients. In contrast, no responses (NRs) were documented in 13 patients with other types of cutaneous T-cell lymphoma, including five mycosis fungoides. Two of five patients with large granular lymphocyte (LGL) leukemia had a CR and two of four with Sézary cell leukaemia had a PR. A low response rate was observed in 27 patients with peripheral T-non-Hodgkin's lymphoma (T-NHL) (19%) and in 25 with adult T-cell leukemia/lymphoma (ATLL) (12%). The latter included two CRs and one PR. Toxicity was low and DCF was generally well tolerated. No significant differences were observed when results were analyzed according to previous treatment. Disease subtype was the most important factor to influence results.We conclude that DCF is effective as a single agent in T-PLL, Sézary syndrome, and LGL leukemia, but has low activity in other T-cell disorders.
Tumor Cell Threshold Required for Suppression of Macrophage Inflammation 2 3
Authors: Sigurd J. Normann
Journal: JNCI Journal of the National Cancer Institute (1978)

In DBA/2 mice bearing transplanted, syngeneic P815 mastocytoma, macrophage accumulation was impaired in the tumor when the cancer grew intraperitoneally. By varying the number of transplanted mastocytoma cells and quantitating the macrophage response to a standardized stimulus of proteose peptone, we determined that 4-16×106 mastocytoma cells were required to inhibit monocyte inflammation. That interference with monocyte inflammation required a threshold number of tumor cells was consistent with an increase in tumor-associated macrophages proportional to tumor growth during early cancer. It was also consonant with a greater number of macrophages in tumors initiated with small rather than large tumor inocula. Impairment of monocyte inflammation could be passively transferred with ascitic fluid.
Glucocorticoid-induced Insulin Resistance
Authors: Jose F. Caro, John M. Amatruda
Journal: Journal of Clinical Investigation (1982)

We have recently proposed that "down regulation" of the insulin receptor may be one of the many biological responses of a cell to insulin. In an attempt to further explore this hypothesis we have studied insulin action, binding, and degradation in freshly isolated hepatocytes from rats rendered insulin resistant by the administration of dexamethasone, 1.0 mg/kg every other day, for 1 and 4 wk, and in dexamethasone-treated (0.1 μM for 24 h) primary cultures of hepatocytes from normal rats.