tbuckley/cabot-search huggingface dataset:
Tumour-associated macrophages in nonsmall cell lung cancer: the role of interleukin-10
Authors: L. M. Montuenga, R. Pio
Journal: European Respiratory Journal (2007)

The origin, progression and dissemination of solid tumours are strongly regulated by stromal, endothelial or defence-related cells 1. Tumour cells do not merely grow into an inert interstitial tissue, but they actively interact with their microenvironment establishing cell-to-cell contacts, releasing soluble factors and responding to soluble factors released by neighbouring cells. In recent years, evidence has been accumulated to support a dual role for macrophages in the regulation of tumour cell proliferation, invasion, angiogenesis or immune control 2, 3. On one hand, the “resident” tissue macrophages have a cytotoxic function against tumour development as they are a major component of the inflammatory infiltrate frequently seen in primary tumours. On the other hand, a different phenotype of monocyte-derived “tumour-associated macrophages” (TAMs) shows opposite behaviour with a commonly pro-tumoral phenotype. The ability of macrophages to promote or inhibit neoplasia seems to depend on their differentiation and activation states 4, 5. At least two major functional states have been described for macrophages and named as M1 and M2. Classically activated M1 macrophages are induced by interferon-γ alone or in combination with lipopolysaccharide and tumour necrosis factor-α. M1 macrophages produce high levels of inducible nitric oxide synthase and pro-inflammatory cytokines, such as interleukin (IL)-12, and are generally considered as part of the inflammatory response against cancer progression. In contrast, M2 macrophages express arginase I, promote angiogenesis, favour tissue remodelling and invasion, and are able to inhibit the inflammatory response through the secretion of IL-10. Thus M2 macrophages are thought to exert a tumour-promoting activity. In most of the solid tumour types that have been analysed so far, TAMs show an M2 differentiation profile, correlate with microvessel density and are associated with reduced patient survival. Redente et al. 6 have recently published a detailed analysis of the changes in activation …
Life in the Womb
Authors: A. DA. Bellairs
Journal: BMJ (1972)

<h3>Objective:</h3> To evaluate the effect of masupirdine on agitation/aggression and psychosis sub-domains of the 12-item neuropsychiatric inventory (NPI-12) scale in patients with dementia of the Alzheimer’s type (AD). <h3>Background:</h3> AD is the most common type of neurodegenerative disorder in older people. Cognitive and neuropsychiatric symptoms are the cardinal clinical features of the disease. Masupirdine has been evaluated in arandomized, double-blind, 26-week, placebo-controlled proof of concept Phase-2 clinical trial in subjects with moderate AD (NCT02580305). <h3>Design/Methods:</h3> Subgroup analyses were carried out on the agitation/aggression, and psychosis domains of the NPI-12 scale. Analyses were based on the independent patient subgroups with baseline symptoms. A mixed-effects model for repeated measures was used to determine the effect of masupirdine in modified intention to treat population. <h3>Results:</h3> A statistically significant (p&lt;0.01) reduction in agitation/aggression scores was observed in patients treated with masupirdine (50 &amp; 100 mg) at Week 13 and the effect sustained till the end of treatment (Week26). Clinically meaningful effect(Cohen’s <i>d</i> - 0.66) was observed in the masupirdine 50 mg treatment arm at Week 26. In the subgroup of population with baseline psychotic symptoms and/or symptoms emergence, a significant reduction (p&lt;0.05) in psychosis score was observed in the masupirdine 50 mg arm at Week 4 &amp; 13. A trend was observed in the masupirdine 100 mg (p&lt;0.1) arm (Week 26). Effect size (Cohen’s <i>d</i>) observed with masupirdine (50 &amp; 100 mg) was 0.32 – 0.50 and 0.25 – 0.39 at the end of 13 and 26 weeks, respectively. Masupirdine had also showed beneficial effects on cognition in patients with psychosis. <h3>Conclusions:</h3> Further exploration of masupirdine is warranted to confirm the beneficial effects on agitation and psychosis. Currently, a Phase-3 study evaluating the effect of masupirdine on agitation in patients with dementia of the Alzheimer’s type is in progress. <b>Disclosure:</b> Dr. Nirogi has nothing to disclose. Mr. Badange has nothing to disclose. Mr. Mohammed has nothing to disclose. Mr. Pandey has nothing to disclose. Mr. BENADE has nothing to disclose. Ramkumar Subramanian has nothing to disclose. Pradeep Jayarajan has nothing to disclose. Jyothsna Ravula has nothing to disclose. Satish Jeta has nothing to disclose.
p53 Pathway in Renal Cell Carcinoma Is Repressed by a Dominant Mechanism
Authors: Katerina V. Gurova, Jason E. Hill, Olga V. Razorenova, Peter M. Chumakov, Andrei V. Gudkov
Journal: Cancer Research (2004)

Abstract Renal cell carcinoma (RCC) rarely acquires mutations in p53 tumor suppressor gene, suggesting that p53 signaling in this tumor type might be repressed by some other mechanism. In fact, all four RCC-derived cell lines we tested maintained wild-type p53 but were not capable of transactivating p53-responsive reporters and endogenous p53-responsive genes. p53 protein in RCC showed normal response to genotoxic stress, including accumulation, nuclear translocation, and activation of specific DNA binding. Functional and expression analysis of Mdm2, MdmX, and Arf showed lack of involvement of these p53 regulators in the observed defect of p53 function in RCC. However, activation of p53-mediated transactivation could be achieved by extremely high levels of p53 attained by lentivirus vector-driven transduction, suggesting the involvement of a dominant inhibitor in repression of p53-dependent transactivation in RCC. Consistently, p53 inactivation prevailed in the hybrids of RCC cells with the cells possessing fully functional p53. Remarkably, cells of normal kidney epithelium also caused partial p53 repression in cell fusion experiments, suggesting that RCC-specific p53 repression may be based on an unknown dominant mechanism also acting in normal kidney tissue.
Relations of Insulin Sensitivity to Longitudinal Blood Pressure Tracking
Authors: Johan Ärnlöv, Michael J. Pencina, Byung-Ho Nam, James B. Meigs, Caroline S. Fox, Daniel Levy, Ralph B. D’Agostino, Ramachandran S. Vasan
Journal: Circulation (2005)

The relations of insulin sensitivity (IS) to hypertension incidence may vary according to baseline age, body mass index (BMI), and blood pressure (BP).We investigated the relations of IS (insulin sensitivity index, ISI(0,120)) to 4-year incidence of hypertension and BP progression in 1933 nonhypertensive Framingham Study participants (median age, 51 years; 56% women). Analyses were stratified by age (less than versus greater than or equal to median), BMI (<25 [normal], 25 to <30 [overweight], > or =30 kg/m2 [obese]), and BP category (systolic BP> or =130 or diastolic BP> or =85, "high normal" per the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP [JNC-VI] versus BP<130/85 mm Hg). On follow-up, 41% of participants had BP progression (> or =1 BP stage increase) and 18% had development of hypertension (systolic BP> or =140 or diastolic BP> or =90 mm Hg or antihypertensive medication use). In younger (<51 years) people with normal BMI and baseline BP<130/85 mm Hg, the second-to-fourth ISI(0,120) quartiles were associated with lower multivariable-adjusted odds for hypertension incidence (0.27; 95% CI, 0.09 to 0.83; P<0.05) and BP progression (0.37; 95% CI, 0.18 to 0.77; P<0.01) relative to the lowest (most insulin resistant) quartile. IS was not related to BP progression or hypertension incidence in older individuals, in obese participants, or in people with BP> or =130/85 mm Hg.In our large community-based sample, reduced IS predicted BP tracking principally in younger people with normal BMI and BP<130/85 mm Hg. Effect modification by age, BMI, and baseline BP may explain variation in the results of prior clinical investigations relating IS to hypertension incidence.
Efficacy of thrombolytic agents in the treatment of pulmonary embolism
Authors: T. Capstick, M. T. Henry
Journal: European Respiratory Journal (2005)

Recent guidelines recommend bolus-dose alteplase for treating massive pulmonary embolism (PE). However, the safest and most effective treatment is as yet unknown. In the present study, a meta-analysis of published studies of alteplase infusion, bolus-dose alteplase and streptokinase was performed. The outcome measures were as follows: objective assessment of thrombolysis; all-cause mortality; deaths due to initial PE, major bleeding episodes and recurrent PE; and morbidity. In total, 26 studies were identified; however, only two comparative studies of alteplase infusion versus either bolus-dose alteplase or streptokinase were found. Meta-analysis revealed no significant difference between the three regimens, but was compromised by a paucity of data. Crude analysis of summated data on thrombolytic efficacy from all studies revealed that alteplase infusion was more effective than bolus-dose alteplase (relative risk (RR): 1.95; 95% confidence interval (CI): 1.19–3.2), whereas streptokinase was more effective than alteplase infusion (RR: 1.27; 95% CI: 1.09–1.47). Alteplase infusion had a lower mortality due to the initial PE than both bolus-dose alteplase and streptokinase (RR: 0.16; 95% CI: 0.05–0.59 and RR: 0.13; 95% CI: 0.04–0.46, respectively). In conclusion, this evidence suggests that the three thrombolytic agents may vary in efficacy. However, large-scale randomised controlled trials are needed to confirm these results.
Procoagulant Platelets
Authors: Elisabeth M. Battinelli
Journal: Circulation (2015)

A bnormalities in coagulation are a leading cause of disease and death worldwide because of thrombotic events such as myocardial infarction, stroke, etc.It has been estimated that the cost of treatment of these disorders will rise to >820 billion by the year 2030. 1 At the center of thrombus formation is the platelet, a cell that is seen as the cornerstone of hemostasis and thrombosis.Platelets mainly function to secure hemostasis by acting as the band-aids of the blood.They are the first responders to sites of vascular injury, bringing with them a membrane surface that provides the glue for clot formation, and a number of proteins essential for coagulation, as well.Platelet involvement ultimately leads to thrombin generation and clot stabilization through fibrin formation.
Racial Disparities in the Association between Birth Weight in the Term Infant and Blood Pressure at Age 7 Years
Authors: Anusha H. Hemachandra, Mark A. Klebanoff, Susan L. Furth
Journal: Journal of the American Society of Nephrology (2006)

BP has been inversely associated with birth weight in studies worldwide, but few studies have included black individuals. The US National Collaborative Perinatal Project followed 58,960 pregnant women and their resultant offspring for 7 yr. In this post hoc analysis, all term white or black children without kidney or heart disease were included (n = 29,710). The effect of birth weight and other risk factors on systolic (SBP) and diastolic BP (DBP) was evaluated at 7 yr. Mean birth weight and body mass index at 7 yr were slightly lower for black compared with white children (birth weight 3.14 ± 0.48 versus 3.32 ± 0.46 kg [P < 0.001]; body mass index 15.8 ± 2.0 versus 16.3 ± 2.0 [P < 0.001]). Compared with white mothers, black mothers were less likely to smoke (41 versus 52%), were more anemic (23 versus 7%), and were more likely to live in poverty (72 versus 39%). In linear regression, there was significant interaction between race and birth weight in predicting SBP (P = 0.002). In bivariate analysis, birth weight was positively associated with SBP (β = 0.87) and DBP (β = 1.14) in black children (P < 0.001) but not associated with either in white children. With maternal poverty, educational level, and anemia during pregnancy added to the model, birth weight remained a significant positive predictor of SBP (β = 0.89, P < 0.001) in black but not in white children (β = 0.02, P = 0.17). The association between birth weight and SBP differs between black and white children. The cause of intrauterine growth restriction–associated hypertension seems to be race sensitive; therefore, future studies of racial disparities in the "Barker hypothesis" may help in the understanding of the mechanism of fetal programming of hypertension.
Suicidal ideation among outpatients at general neurology clinics: prospective study
Authors: A. J Carson
Journal: BMJ (2000)

<h3>Abstract</h3> Specialized pro-resolving mediators (SPMs) actively limit inflammation and expedite its resolution. Here we profiled intramuscular lipid mediators following injury and investigated the role of SPMs in skeletal muscle inflammation and repair. Both eicosanoids and SPMs increased following myofiber damage induced by intramuscular injection of barium chloride or functional overload. Daily systemic administration of resolvin D1 (RvD1) limited the degree and duration of inflammation, enhanced regenerating myofiber growth, and improved recovery of muscle strength. RvD1 suppressed inflammatory cytokines, enhanced polymorphonuclear cell clearance, modulated muscle stem cells, and polarized macrophages to a more pro-regenerative subset. RvD1 had minimal direct impact on <i>in-vitro</i> myogenesis but directly suppressed myokine production and stimulated macrophage phagocytosis, showing that SPMs influence modulate both infiltrating myeloid and resident muscle cells. These data reveal the efficacy of immunoresolvents as a novel alternative to classical anti-inflammatory interventions in the management of muscle injuries to modulate inflammation while stimulating tissue repair.
P103 Do Children With Primary Ciliary Dyskinesia Harbour The Same Pathogens In The Upper And Lower Airway?
Authors: G. Marsh, N. Collins, A. Bush, C. Hogg, S. Carr
Journal: Thorax (2014)

<h3>Background</h3> Primary ciliary dyskinesia (PCD) is characterised by chronic nasal discharge and lower respiratory tract infections. We aimed to assess the prevalence and concordance of pathogens present in samples from the upper (UA) and lower airway (LA) of children with PCD. <h3>Method</h3> Microbiology samples from UA (naso-sinal lavage or nasal swab) and LA (sputum or cough swabs) were taken at the same time from children attending a specialist PCD centre, diagnosed on standard criteria (Eur Respir J 2009:34:1264–1276). <h3>Results</h3> 70 children (30 male), median age 10.7 yrs (range 1–18), were studied. 36/70 were prescribed long term prophylactic oral antibiotics. 42 (60%) of UA samples were culture positive compared to 21 (30%) positive LA samples. The UA positive group were not statistically different in age or FEV<sub>1</sub>% pred (11.1 vs 10 yrs and 78% vs 75%). 14 patients were culture positive in both UA and LA, 10 of which had matched pathogens and 4 were unmatched. 20 were matched culture negative. The range of pathogens and where they were isolated are shown in the Table, some samples had more than one isolate. Note the Table shows concordance for same pathogens <h3>Conclusion</h3> In PCD, pathogens are isolated far more commonly from the UA than the LA. The clinical impact of these pathogens in the long term is unknown. 11 (16%) had PA in UA with only 2 of these having PA in their LA. We speculate that the UA may be, at least in some children, the source of LA infection. Clinical trials of eradication therapy after positive nasal cultures are indicated
Particulate air pollution and hospital admissions for cardiorespiratory diseases: are the elderly at greater risk?
Authors: H.R. Anderson, R.W. Atkinson, S.A. Bremner, L. Marston
Journal: European Respiratory Journal (2003)

A systematic literature review suggests that particulate air pollution is associated with daily admissions for both respiratory and cardiac diseases in people aged &gt;65 yrs. A model of acute effects is proposed which shows how admissions can be brought forward by a relatively short period of time as well as events being added that would not have happened at all except for air pollution. A model of the effects of air pollution on chronic disease is proposed that provides the background of long-term vulnerability upon which the increased short-term vulnerability is superimposed. A study of daily hospital admissions in London shows that for respiratory disease the relative risks of admission associated with particles reduce with increasing age, while for cardiac disease, there is no trend. When the attributable risk is estimated using baseline admission rates for respiratory disease, it is children who have the highest attributable risk, followed by the elderly. For cardiac disease there is a steep increase in attributable risk with age, reflecting the dominant influence of baseline risks. The attributable risk for cardiovascular disease in the elderly is considerably greater than for respiratory disease, due to higher baseline admission rates.
Bivalirudin Started during Emergency Transport for Primary PCI
Authors: Philippe Gabriel Steg, Arnoud van 't Hof, Christian W. Hamm, Peter Clemmensen, Frédéric Lapostolle, Pierre Coste, Jurrien Ten Berg, Pierre Van Grunsven, Gerrit Jan Eggink, Lutz Nibbe, Uwe Zeymer, Marco Campo dell' Orto, Holger Nef, Jacob Steinmetz, Louis Soulat, Kurt Huber, Efthymios N. Deliargyris, Debra Bernstein, Diana Schuette, Jayne Prats, Tim Clayton, Stuart Pocock, Martial Hamon, Patrick Goldstein
Journal: New England Journal of Medicine (2013)

Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown.We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding.Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients.Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.).
Bridging Population and Tissue Scale Tumor Dynamics: A New Paradigm for Understanding Differences in Tumor Growth and Metastatic Disease
Authors: Jill Gallaher, Aravind Babu, Sylvia Plevritis, Alexander R.A. Anderson
Journal: Cancer Research (2014)

To provide a better understanding of the relationship between primary tumor growth rates and metastatic burden, we present a method that bridges tumor growth dynamics at the population level, extracted from the SEER database, to those at the tissue level. Specifically, with this method, we are able to relate estimates of tumor growth rates and metastatic burden derived from a population-level model to estimates of the primary tumor vascular response and the circulating tumor cell (CTC) fraction derived from a tissue-level model. Variation in the population-level model parameters produces differences in cancer-specific survival and cure fraction. Variation in the tissue-level model parameters produces different primary tumor dynamics that subsequently lead to different growth dynamics of the CTCs. Our method to bridge the population and tissue scales was applied to lung and breast cancer separately, and the results were compared. The population model suggests that lung tumors grow faster and shed a significant number of lethal metastatic cells at small sizes, whereas breast tumors grow slower and do not significantly shed lethal metastatic cells until becoming larger. Although the tissue-level model does not explicitly model the metastatic population, we are able to disengage the direct dependency of the metastatic burden on primary tumor growth by introducing the CTC population as an intermediary and assuming dependency. We calibrate the tissue-level model to produce results consistent with the population model while also revealing a more dynamic relationship between the primary tumor and the CTCs. This leads to exponential tumor growth in lung and power law tumor growth in breast. We conclude that the vascular response of the primary tumor is a major player in the dynamics of both the primary tumor and the CTCs, and is significantly different in breast and lung cancer.
Metabolomic NMR Fingerprinting to Identify and Predict Survival of Patients with Metastatic Colorectal Cancer
Authors: Ivano Bertini, Stefano Cacciatore, Benny V. Jensen, Jakob V. Schou, Julia S. Johansen, Mogens Kruhøffer, Claudio Luchinat, Dorte L. Nielsen, Paola Turano
Journal: Cancer Research (2011)

Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ((1)H-NMR) to profile the serum metabolome in patients with mCRC and determine whether a disease signature may exist that is strong enough to predict overall survival (OS). In 153 patients with mCRC and 139 healthy subjects from three Danish hospitals, we profiled two independent sets of serum samples in a prospective phase II study. In the training set, (1)H-NMR metabolomic profiling could discriminate patients with mCRC from healthy subjects with a cross-validated accuracy of 100%. In the validation set, 96.7% of subjects were correctly classified. Patients from the training set with maximally divergent OS were chosen to construct an OS predictor. After validation, patients predicted to have short OS had significantly reduced survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of mCRC and that analysis of this signature may offer an independent tool to predict OS.