tbuckley/cabot-search huggingface dataset:
The pharmacology of mechanogated membrane ion channels.
Authors: O P Hamill, D W McBride
Journal: Pharmacological Reviews (1996)

In this article, the actions, mechanisms and applications of various ions and drugs that interact with MG channels have been discussed. At present, no compound has been found that displays the high specificity and affinity exhibited by tetrodotoxin or alpha-bungarotoxin that proved so useful in the functional and structural characterization of the voltage-gated Na+ channel and the acetylcholine receptor channel, respectively. Nevertheless, three different classes of compounds have been discovered since Paintal's review that clearly block MG channels. These compounds, represented by amiloride, gentamicin and gadolinium, act mainly on the SA cation channel, which appears to be shared by many nonsensory and some mechanosensory cells. Each class of compound can be distinguished by the voltage and concentration dependence of the block and most likely involves different mechanisms of blocking action. In general, the MG channel blocker pharmacology indicates a variety of "receptor sites" on MG channels. The recognition and acceptance of such receptors should provide added impetus for continued screening for more potent drugs, venoms and toxins. In the case of activators, little is understood of the mechanisms by which the various amphipathic and amphiphilic compounds stimulate MG channels, although different bilayer and protein mechanisms have been evoked. Even less is understood of the role the new class of MG K+ channel and their modulation by fatty acids plays in physiological and perhaps pathological processes. However, given that K+ channels in general tend to reduce the excitability of nerve and muscle, plausible roles include fatty acid regulation of vascular tone and control of neuronal network excitability. In both cases, more detailed understanding is required regarding the physiological stimuli that modulate these channels through their fatty acid receptors. It may turn out that recognition and/or development of cell-type specific agents that activate such MG channels will possess high therapeutic potential. In any case, the observation that MG channels can be chemically blocked and/or activated by a wide range of compounds requires revision of the long-standing conclusion of Paintal that mechanotransduction is a process that has a low susceptibility to chemical influence.
Smoking ban cuts admissions for child respiratory infections
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Banning smoking in public places has cut hospital admissions for childhood respiratory infections in England by 11 000 a year, new research has estimated.

Researchers from the United Kingdom and the Netherlands said that evidence has shown that smoke-free public environments will benefit children’s health but that the exact effect on respiratory tract infections is unclear. They analysed more than 1.6 million cases of …
Letter by Kruszelnicka et al Regarding Article, “Evidence That Links Loss of Cyclooxygenase-2 With Increased Asymmetric Dimethylarginine: Novel Explanation of Cardiovascular Side Effects Associated With Anti-Inflammatory Drugs”
Authors: Olga Kruszelnicka, Ewa Wieczorek-Surdacka, Andrzej Surdacki
Journal: Circulation (2015)
Fusion of a Novel Gene, BTL, to ETV6 in Acute Myeloid Leukemias With a t(4;12)(q11-q12;p13)
Authors: Jan Cools, Chrystèle Bilhou-Nabera, Iwona Wlodarska, Christine Cabrol, Pascaline Talmant, Philippe Bernard, Anne Hagemeijer, Peter Marynen
Journal: Blood (1999)
Non-steroidal anti-inflammatory drugs in the treatment of hyper-IgD syndrome
Authors: P PICCO, M GATTORNO, M DI ROCCO, A BUONCOMPAGNI
Journal: Annals of the Rheumatic Diseases (2001)

Hyper-IgD syndrome (HIDS) is due to mutations of the gene coding for mevalonate kinase, an enzyme that has a pivotal role in the synthesis of isoprenoids and cholesterol.1 So far, there is no consensus about how HIDS should be treated. Here we report our experience with a child with HIDS treated with different drug regimens.

The child was born to healthy, unrelated Italian parents. He came to our attention because of periodic fever spikes, which occurred every 20–30 days. During fever flare ups, he usually developed chills, arthralgias without arthritis, malaise, and abdominal pain with diarrhoea. Severe leucocytosis (up to 39 × 109/l) and acute phase reactant positivity (C reactive protein 2.9 mg/l; normal values <4 mg/l) were also detected. An abdominal echo …
Clinical effectiveness of antidepressive drug in patients with COPD and concomitant moderate depressive episode
Authors: Yira Feshchenko, Ludmila Iashyna, Maryna Polianska, Inna Zvol, Alyona Potocjniak, Ludmila Savelieva
Journal: European Respiratory Journal (2013)

Aim of study:   to study the effectiveness of agomelatin on clinical symptoms in COPD patients with moderate depressive episode (DE). Study was carried out because of budjet cost.    Materials and methods  : 19 COPD (post BD FEV1/FVC  15), 7 female and 12 male, mean age (61,7 ± 2,6) years received agomelatin 25 mg 1 hour before sleep OD during 4 weeks on the background of standard COPD therapy according severity. Depressive episode was verified by psychiatrist. Patients were assessed with questionnaires PHQ-9, MADRS, mMRC, CAT score, EQ-5D, also were performed 6-min walk test with BORG scale (physical tolerability) in baseline, in 2 and 4 weeks.    Results:   Signs of depression significantly (p    Conclusion  : use of agomelatin in complex COPD therapy in patients with COPD and moderate depressive episode caused decrease of depressive signs after 2 weeks of therapy with further improvement to 4 week. Clinical signs of COPD, including tolerability of physical load also improved (p
A myeloid NF-κΒ response in malignant pleural effusion
Authors: Magda Spella, Anastasios D. Giannou, Antonia Marazioti, Dimitrios Kardamakis, Georgios T. Stathopoulos
Journal: European Respiratory Journal (2013)

Malignant pleural effusion (MPE) is a phenotype of cancer that heavily rests on inflammatory tumor-host interactions (Stathopoulos, G.T. et al. Am J Respir Crit Care Med 2012;186:487-92). The impact of host nuclear factor (NF)-κB, a key proinflammatory pathway, on MPE development has not been elucidated. Here we used bioluminescence imaging of relevant reporter mice, adoptive bone marrow transfer (BMT) and molecular phenotyping to map host NF-κΒ activation during MPE formation. For this, MPE-competent (LLC lung adenocarcinoma, MC38 colon adenocarcinoma and AE17 pleural mesothelioma) and –incompetent (B16F10 melanoma) wild-type tumor cells were delivered to the pleural space of NF-κΒ reporter mice (NF-κB.GFP.Luciferase; NGL) followed by serial bioluminescent imaging. In this model, GFP and luciferase reporter expression is restricted to host cells with active NF-κΒ. A strong thoracic NF-κB response was triggered specifically by MPE-competent tumor cells and coincided with MPE development. Using BMT of wt or NGL bone marrow to wt or NGL recipients, we identified that this host NF-κΒ response was transplantable with NGL-donated bone marrow. Immunophenotyping of GFP+ cells identified myeloid cells as the source of the NF-κΒ signal. Clodronate-mediated ablation of pleural myeloid cells during MPE formation significantly abrogated the potential of MPE-competent tumor cells to give rise to MPE.  These studies suggest a tumor-promoting role for myeloid NF-κΒ activation in the malignancy-affected pleural space, providing evidence that, in addition to tumor cell-NF-κΒ, activation of the transcription factor in host immune cells may present a marked therapeutic target in patients with MPE.  These studies were supported by a ERC Grant.
Ethnicity and breast cancer in the Women's Health Initiative: A unifying concept for unfavorable outcome in African American women
Authors: R. T. Chlebowski, Z. Chen, T. Rohan, A. Aragaki, D. Lane, N. Dolan, E. Paskett, R. Patterson, A. Hubbell, R. Prentice
Journal: Journal of Clinical Oncology (2004)

1008 Background: The lower breast cancer incidence in minorities and higher breast cancer mortality in African Americans compared to Whites are largely unexplained. Therefore, relationships among ethnicity/race, breast cancer risk factors, and breast cancer were explored in an ethnically diverse cohort. Methods: Following comprehensive risk assessment, 156,570 postmenopausal WHI participants (129,037 White, 14,170 Black, 6,388 Hispanic, 4,114 Asians, 2,165 unknown and 696 American Indian) age 50 to 79 years were prospectively followed for breast cancer. Results: During 6.3 yrs median follow-up, 3938 invasive breast cancers were identified in 3455 Whites, 242 Blacks, 103 Hispanics, 88 Asians, 39 unknowns and 11 American Indians. Age-adjusted incidence rates for all minorities were lower compared to Whites. The ethnic differences approached unity and were largely explained by analysis models incorporating risk factor distribution and mammography use for Hispanics and Asians. However, for African Americans a significantly (p=0.02) lower incidence persisted (HR 0.82; 95% CI 0.69,0.96) after risk factor incorporation. African Americans had unfavorable cancers with combined poor/anaplastic grade plus ER negative cancers in 33% of cases vs 10% in Whites (OR 4.72, 95% CI 3.18,7.02).Mortality after breast cancer was greater in African Americans (HR 1.79; 95% CI 1.05,3.05). Obesity (Body Mass Index (BMI)≥30kg/m2), seen in most (51%) African American women, was only a modest (p=0.16) predictor of unfavorable characteristics compared to African American ethnicity which was strongly (p<0.0001) associated with risk of poor/anaplastic grade plus ER negative cancers.Conclusions: Breast cancer risk factors have similar influence across ethnicity. In African American a high proportion of unfavorable cancers associated most strongly with ethnicity plausible explains the increased breast cancer mortality seen. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Combined stool-based multiplex PCR and microscopy for enhanced pathogen detection in patients with persistent diarrhoea and asymptomatic controls from Côte d’Ivoire
Authors: S L Becker, J K Chatigre, J-P Gohou, J T Coulibaly, R Leuppi, K Polman, F Chappuis, P Mertens, M Herrmann, E K N'Goran, J Utzinger, L von Müller
Journal: Clinical Microbiology and Infection (2015)
Does Palliative Chemotherapy Palliate? Evaluation of Expectations, Outcomes, and Costs in Women Receiving Chemotherapy for Advanced Ovarian Cancer
Authors: Catherine Doyle, Michael Crump, Melania Pintilie, Amit M. Oza
Journal: Journal of Clinical Oncology (2001)

The value of palliative chemotherapy in women with refractory and recurrent ovarian cancer is difficult to quantify, and little is known about patient expectations from these treatments. We evaluated in the current prospective study patient expectations, palliative outcomes of chemotherapy, and the inherent resource utilization in patients undergoing second- or third-line chemotherapy for recurrent or refractory advanced ovarian cancer.The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ C30) and Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaires were used to assess palliative benefit and an in-house questionnaire was used to gauge patient expectations. The minimal clinically important difference (MCID) was calculated by asking women to make a global rating of change and correlating this to the EORTC QLQ C30. Resource use was recorded and costs were calculated.Twenty-seven patients were accrued. Objective response was documented on seven of 27. The median survival was 11 months. Sixty-five percent of women expected that chemotherapy would make them live longer and 42% that it would cure them. After two cycles, quality-of-life (QL) improvement was seen particularly in global function (11 of 21) and emotional function (13 of 21) with EORTC QLQ C-30. Improvement was sustained for a median of 2 and 3 months, respectively, in these categories. The MCID was calculated to be 0.39 on a seven-point scale for physical function and 0.13 for global function. The mean total cost per patient for the study period was Can $12,500.Patient expectations from these treatments are often unrealistic. Although objective responses are low, active palliation with chemotherapy is associated with substantive improvement in patients' emotional function and global QL, with overall costs that seem relatively modest.
Epilepsy after Craniotomy and the Place of Prophylactic Anticonvulsant Drugs: Discussion Paper
Authors: M D M Shaw, P M Foy
Journal: Journal of the Royal Society of Medicine (1991)

A retrospective study of 1000 patients who had undergone supratentorial neurosurgery and with prolonged follow-up revealed an overall postoperative incidence of epilepsy of 17%. The incidence varied with different pathologies but anticonvulsants given prophylactically in a randomized trial did not significantly alter the incidence. Routine anticonvulsant prophylaxis cannot be recommended.
The increase of circulating B7-H4-expressing CD68+ macrophage correlated with clinical stage of lung carcinomas
Authors: Jian An Huang, Cheng Chen, Yibei Zhu, Xueguang Zhang
Journal: European Respiratory Journal (2012)

Purpose  To investigate the B7-H4-expressing TAM in a series of 56 cases of lung carcinoma.   Methods  Tissue samples were obtained from patients with lung cancer, who underwent lobectomy surgery. B7-H4-expressing TAM was observed by confocal microscopy. B7-H4-expressing macrophage (CD68 +  cells) in peripheral blood was compared among patients with lung cancer, patients with tuberculosis and healthy donors by two-color flow cytometry. Correlation of B7-H4-expressing CD68 +  macrophage with histological types, tumor size and lymph node metastasis was analyzed.   Results  Lung cancer are infiltrated with Tumor-associated macrophages (CD68 +  cells) that expressed B7-H4.The circulating B7-H4-expressing CD68 +  cell were higher in the lung cancer group than in the tuberculosis group. The number of B7-H4-expressing CD68 +  cells was significantly correlated with the lymph node metastasis, and the tumor size. The proportion of B7-H4 positive CD68 +  cells among CD68 +  cells was also greater in late stage lung cancer than in serous early stage lung cancer. The intensity of B7-H4 staining was significantly correlated with lymph node metastasis, and the tumor size. Expression of B7-H4 was significantly higher in CD68 +  cells from the late stage lung cancer (stage III-IV, n=36) as compared with the CD68 +  cells from early stage lung cancer (stage I-II, n=20).   Conclusion  It is suggested that lung carcinomas increase B7-H4-expressing macrophages, which might favor tumor progression.
Recall Helper T Cell Response
Authors: Mark A. Aronica, Susan McCarthy, Shadi Swaidani, Daphne Mitchell, Mehmet Goral, James R. Sheller, Mark Boothby
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Effector and memory T lymphocytes differ significantly, and there is no experimental evidence that memory cells are sufficient to render an otherwise normal individual susceptible to localized allergic inflammation. Furthermore, nothing is known about the kinetics of memory responses after inhalation of antigen or interplay between an allergen-specific memory helper T (Th) cell Th2 population and uncommitted or competing Th1 cells. To study these processes, T cell receptor–transgenic CD4+ effector cells were generated in vitro, transferred into naive recipients, and allowed to resume a quiescent state. Inhalation of protein antigen reactivated these Ag-specific Th2 donor cells, leading to allergic pulmonary inflammation and airway hyperreactivity. Susceptibility was correlated with the size of the input Th2 population, but Th1 cells neither enhanced nor reduced inflammation in this model. Importantly, the reactivation of these antigen-experienced cells by inhaled antigen did not skew the cytokine balance of recipient-derived T cells recruited to the lung nor did it inhibit the development of donor-derived Th1 cells from uncommitted antigen-experienced cells that form a normal part of immune responses. These data indicate that a quiescent memory Th2-cell population can create susceptibility to allergic pulmonary inflammation in a manner refractory to inhibition by Th1 cells or endogenous inhibitory mechanisms.
Inhibition of Intestinal Carcinogenesis in Rats: Effect of Difluoromethylornithine With Piroxicam or Fish Oil&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N D Nigro, A W Bull, M E Boyd
Journal: JNCI Journal of the National Cancer Institute (1986)

An inhibitor of ornithine decarboxylase, difluoromethylornithine (DFMO), and two inhibitors of prostaglandin biosynthesis, piroxicam and menhaden fish oil, were examined for their effect on intestinal tumorigenesis in male Sprague-Dawley rats fed a 5% fat semisynthetic diet. Each agent was given individually in one of two doses as follows: DFMO, 0.05% and 0.1% in the drinking water; piroxicam, 65 mg/kg diet and 130 mg/kg diet; and menhaden fish oil, 1.25% and 2.50% of the diet. Additional animal groups were given combinations of the lower dose of DFMO and the lower dose of either Piroxicam or fish oil. Intestinal tumors were induced by sc injections of azoxymethane (AOM; CAS: 25843-45-2) at 8 mg/kg (body wt) weekly for 8 weeks. Test diets were started 1 week prior to the first dose of AOM, and the rats were sacrificed 26 weeks later. Rats that received either dose of DFMO or the high dose of piroxicam developed significantly fewer intestinal tumors compared to controls. The low dose of piroxicam and the fish oil given at either dose level had no effect. The combination of the low dose of DFMO and the low dose of piroxicam reduced tumor formation more than either dose of DFMO alone, whereas the low dose of DFMO and fish oil together was no more effective than either dose of DFMO alone. These results show that a combination of a small amount of DFMO and piroxicam, each acting through a different mechanism, exerts an additive inhibitory effect on intestinal tumor formation in rats.
Endotoxin levels in primary schools and homes of Dutch school children
Authors: José Jacobs, Esmeralda Krop, Dick Heederik
Journal: European Respiratory Journal (2011)

Background:  Indoor air quality is essential for children9s health. Several studies describe the variety and extent of indoor pollutant exposure in homes and to a lesser extent in schools. However studies that include both environments in one study are sparse.   Objective:  To assess indoor endotoxin levels in dust and compare levels in primary schools and homes of children.   Methods:  This study is an extension of the European HITEA project. Ten schools with moisture/dampness problems (index) and reference schools were selected, based on building questionnaires and on-site inspections. Airborne dust at several locations in school was passively sampled with Electrostatic Dust fall Collectors (EDC), during 8 weeks in March/April 2010. In the same period, dust was sampled during 2 weeks in 169 children bedrooms from index and reference schools.   Results:  Average endotoxin levels ranged from 4355 to 12101 EU/m 2  in schools, and from 923 to 2570 EU/m 2  in homes, adjusted to a two week sampling period. Both school and home endotoxin levels tended to be higher in the index than in the reference category (average ratio∼1.35). However, within the index category, and also within the reference, variation between schools was higher than between both categories. There was less variation between home endotoxin levels within and between both index and reference categories. Class room occupancy was related to endotoxin levels. Home characteristics associated with endotoxin levels were the number of people living in the house and building age.   Conclusion:  Average endotoxin levels were considerably higher in schools than in homes. Occupancy was significantly related with school and home endotoxin levels. Home age also affects endotoxin levels.
Abstract 17136: Irx3 and Irx5 Cooperatively Regulate Mouse Heart Development and Adult Cardiac Function
Authors: Nathalie Gaborit, Shan-Shan Zhang, John Wylie, Rui Sakuma, Chi-Chung Hui, Benoit G Bruneau
Journal: Circulation (2011)

Transcriptional regulation of heart development takes place via spatio-temporal and coordinated expression of multimeric complexes of transcription factors. Members of the Iroquois homeobox (Irx) family of transcription factors are expressed in highly cell type-specific and often overlapping patterns in the developing heart, suggesting that these genes may interact in important pathways during cardiogenesis. Single deletions of Irx genes showed subtle but significant defects in several aspects of cardiac function, including cardiac repolarization for Irx5, and ventricular conduction for Irx3. Additionally, Irx3 and Irx5 expression overlap in the cardiac ventricular chambers. Our study suggests that their overlapping expression may mask additional roles of these genes in cardiac development and adult function. Supporting a combinatorial role in pre-natal cardiac development, mice lacking both Irx3 and Irx5 are embryonically lethal due to major structural heart defects that model human congenital heart disease, including a common atrio-ventricular canal and a double outlet right ventricle. We show that the cardiac phenotype originates from the loss of function of Irx3 and Irx5 in endocardial cells. In the adult heart, our data suggest that Irx3 and Irx5 double knockout mice have a prolonged QRS complex and PR interval that is worse than the Irx3 single knockout mice. Moreover, the T wave absent in the Irx5 single knockout mice reappears with the additional deletion of Irx3. These results strongly suggest a role for Irx3 and Irx5 in the ventricular conduction of the electrical influx. All together, our data suggest that Irx3 and Irx5 cooperatively regulate heart development and adult cardiac function.
A curriculum for training healthcare workers in the management of highly infectious diseases
Authors: A Baka, F M Fusco, V Puro, N Vetter, P Skinhoj, K Ott, Heli Siikamäki, H R Brodt, R Gottschalk, P Follin, B Bannister, G De Carli, C Nisii, J Heptonstall, G Ippolito
Journal: Eurosurveillance (2007)

Binary file ES_Abstracts_Final_ECDC.txt matches
Malaria vaccine difficult to roll out because four doses are needed, WHO says
Authors: Anne Gulland
Journal: BMJ (2015)

An antimalaria vaccine for children will be piloted in up to five demonstration sites before being recommended for widespread use, a World Health Organization expert committee has announced.

A phase III trial showed that the RTS,S vaccine, which acts against Plasmodium falciparum , had an efficacy of around 30%.1 The vaccine, which is most effective in children aged between 5 months and 17 months, is given in three …