tbuckley/cabot-search huggingface dataset:
4-Hydroxy-2-Nonenal, a Specific Lipid Peroxidation Product, Is Elevated in Lungs of Patients with Chronic Obstructive Pulmonary Disease
Authors: Irfan Rahman, Annemarie A. M. van Schadewijk, Ann J. L. Crowther, Pieter S. Hiemstra, Jan Stolk, William MacNee, Willem I. De Boer
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Cigarette smoking results in oxidative stress and inflammation in the lungs, which are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). 4-Hydroxy-2-nonenal (4-HNE), a highly reactive diffusible product of lipid peroxidation, is a key mediator of oxidant-induced cell signaling and apoptosis. 4-HNE has a high affinity toward cysteine, histidine, and lysine groups and forms direct protein adducts. We investigated the presence of 4-HNE–modified proteins in lung tissue obtained from subjects with and without COPD. We studied 23 current or ex-smokers with similar smoking histories with COPD (n = 11; FEV1 < 70% predicted) or without COPD (n = 12; FEV1 > 84% predicted) who had undergone lung resection. As 4-HNE and transforming growth factor-β1 (TGF-β1) can modulate γ-glutamylcysteine synthetase (γ-GCS) mRNA levels in lung cells, we assessed the relations between 4-HNE–modified protein levels, FEV1, γ-GCS, and TGF-β1. 4-HNE–modified protein levels were elevated in airway and alveolar epithelial cells, endothelial cells, and neutrophils in subjects with COPD, compared with the levels in subjects without COPD (p < 0.01). We also observed a significant inverse correlation between the levels of 4-HNE adducts in alveolar epithelium, airway endothelium, and neutrophils and FEV1 (p < 0.05) and a positive correlation between 4-HNE adducts and TGF-β1 protein and mRNA as well as γ-GCS mRNA levels in airway and alveolar epithelium (p < 0.01). The elevated levels of 4-HNE may play a role in the signaling events in lung inflammation leading to the imbalance of the expression of both proinflammatory mediators and protective antioxidant genes in COPD.
Parents should have absolute rights over child s body after death, report says
Authors: B. Christie
Journal: BMJ (2001)

New laws that would give absolute rights to parents to decide what should happen to a child's body after death are needed in the United Kingdom, a Scottish independent inquiry into organ removal has recommended.

The inquiry, which covered the removal of organs from adults as well as children, was commissioned in the wake of the Alder Hey affair, in which organs were removed from thousands of children without their parents' consent.

The recommendations of the Scottish inquiry go further than what has already been proposed in England and involve the …
Size of the diaphragm in chronic bronchitis
Authors: R. H. Steele, B. E. Heard
Journal: Thorax (1973)

Diaphragms were dissected out intact from 29 male and 9 female cadavers at necropsy. Fifteen of the males and eight of the females were grouped as controls, having no history of chest disease. Fourteen of the males and one female gave a history of chronic bronchitis. Point-counting and other methods were employed to measure the mean area, thickness, and volume of the diaphragmatic muscle, excluding the central tendon. The results showed that the diaphragm was reduced in area, thickness, and volume in the chronic bronchitics, the figures being 350 cm<sup>2</sup>, 0·29 cm, and 99·7 cm<sup>3</sup> respectively in male controls, and 295 cm<sup>2</sup>, 0·23 cm, and 68·7 cm<sup>3</sup> in the bronchitics. In the female controls, the values were significantly lower than in the male controls. The one female bronchitic had a muscle volume of only 40 cm<sup>3</sup>. The male controls were similar in height to the bronchitics, but their mean weight was higher, being 69·4 kg against 56·0 kg in male bronchitics. It is concluded that the diaphragm is smaller in chronic bronchitics than in controls at necropsy and that while a major factor in causation is an associated low body weight, other factors such as the mechanical consequences of flattening of the diaphragm, longstanding reduction in physical activity, and other diseases such as cancer may also play a part. No histological changes by non-quantitative methods were found in the diaphragm in the chronic bronchitics, but muscle fibre shrinkage was suspected. By contrast, a few cases of asthma examined to date have shown no evidence of reduction in diaphragm size. The mechanical implications are discussed.
Assessing Myocardial Viability and Infarct Transmurality With Left Ventricular Electromechanical Mapping in Patients With Stable Coronary Artery Disease
Authors: Emerson C. Perin, Guilherme V. Silva, Rogerio Sarmento-Leite, Andre L.S. Sousa, Marcus Howell, Raja Muthupillai, Brenda Lambert, William K. Vaughn, Scott D. Flamm
Journal: Circulation (2002)

Background— This study was designed to define myocardial viability and establish practical cut-off values for differentiating normal myocardial tissue from subendocardial and transmural scar tissue by using electromechanical mapping (EMM). We validated our results by delayed-enhancement cardiac MRI (DE-MRI). Methods and Results— We prospectively studied 15 ambulatory patients with stable coronary disease who were candidates for cardiac catheterization. Within 48 hours of EMM, DE-MRI was performed. Using EMM software, we created a bull’s eye precisely matched to that generated by DE-MRI. Segment by segment, we compared the MRI results to the corresponding unipolar voltage value for that same segment in the EMM bull’s eye. Of 300 total segments, 275 were compared. The segments were divided into normal (n=211), subendocardial scar (n=49), and transmural scar (n=15). We found that subendocardial (6.8±2.9 mV) and transmural (4.6±1.9 mV) scar segments had significantly less unipolar voltage than normal (11.6±4.5 mV) segments ( P &lt;0.05 for each comparison). When normal myocardium was compared with myocardium with subendocardial scar, the threshold for differentiating between the two areas was 7.9 mV (sensitivity, 80%; specificity, 80%). Comparison of normal tissue to transmural scar yielded a threshold of 6.9 mV (sensitivity, 93%; specificity, 88%). Conclusions— Our results demonstrate that normal myocardium can be accurately distinguished from myocardium with subendocardial or transmural infarcts on the basis of unipolar voltage values obtained through EMM. This is the first study to validate these results by using cardiac DE-MRI in humans.
TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice
Authors: Kathrin Steinwede, Stefanie Henken, Jennifer Bohling, Regina Maus, Bianca Ueberberg, Christina Brumshagen, Erik L. Brincks, Thomas S. Griffith, Tobias Welte, Ulrich A. Maus
Journal: The Journal of Experimental Medicine (2012)

Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae–induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail−/− mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae–infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option.
Controlled trial of an ankle support (Malleotrain) in acute ankle injuries.
Authors: J O'Hara, J C Valle-Jones, H Walsh, H O'Hara, N B Davey, H Hopkin-Richards, R M Butcher
Journal: British Journal of Sports Medicine (1992)

A randomized, controlled parallel-group trial has assessed 14 days' use of a new ankle support (Malleotrain, Bauerfeind, Aldershot, UK) in 220 patients (118 Malleotrain, 102 control group) with acute ankle injuries. Self-assessed pain levels were significantly lower in the group using Malleotrain at the end of the trial (P less than 0.05), as were median times taken for reduction of symptom scores to 10% (P less than 0.05) and total analgesic consumption during the trial (P less than 0.05). Overall clinical assessment scores were significantly superior in the Malleotrain group (P less than 0.02). Of those patients who received Malleotrain, 112 of 116 patients who commented (95% of all Malleotrain-treated patients) did so positively and only one patient stopped wearing the support during the trial. Malleotrain is acceptable to patients with acute ankle injuries and its use increases the rate of alleviation of symptoms. Its use should therefore be considered in the management of all such patients.
Therapeutic Effect of Sentinel Lymph Node Biopsy in Melanoma Remains an Open Question
Authors: Phyllis A. Gimotty, Frank Yoon, Rachel Hammond, Paul Rosenbaum, DuPont Guerry
Journal: Journal of Clinical Oncology (2009)

Phyllis A. Gimotty, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA Frank Yoon, Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA Rachel Hammond, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA Paul Rosenbaum, Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA DuPont Guerry, Department of Medicine, University of Pennsylvania, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA
Circulating cytokines in active polymyalgia rheumatica
Authors: L Alvarez-Rodríguez, M Lopez-Hoyos, C Mata, M Jose Marin, J Calvo-Alen, R Blanco, E Aurrecoechea, M Ruiz-Soto, V M Martínez-Taboada
Journal: Annals of the Rheumatic Diseases (2009)

To characterise the circulating cytokine profile and the cellular source of circulating cytokines in polymyalgia rheumatica (PMR).The study included 34 patients with active untreated PMR and 17 age-matched healthy controls (HC). Circulating cytokines were measured by cytometric bead array and ELISA. Intracellular cytokines were assessed in CD3+ and CD14+ cells by flow cytometry. Cytokines in cell culture supernatants were also determined after polyclonal stimulation of patients' peripheral blood mononuclear cells.Circulating levels of interleukin-6 (IL6) were significantly higher in subjects with active PMR than in HC. Corticosteroid (CS) treatment was followed by a decrease in the level of IL6. Intracellular cytokine staining showed that circulating monocytes did not produce higher amounts of proinflammatory cytokines in patients with PMR than in HC. There was a discordance between serum levels and cytokine-producing monocyte and T cells, and it was not possible to demonstrate a Th1 bias in the peripheral compartment.Active PMR is characterised by increased serum levels of IL6, but not of other proinflammatory cytokines, that are rapidly suppressed by CS treatment. As circulating monocytes do not show increased production of proinflammatory cytokines, IL6 may be mainly produced in the inflamed tissue. A study of the circulating cytokine profile and its cellular source may provide a clue to new therapeutic options.
Effectiveness of treatment with antihypertensive drugs and trends in mortality from stroke in the community.
Authors: J Tuomilehto, A Nissinen, E Wolf, J Geboers, T Piha, P Puska
Journal: BMJ (1985)

A study was made of the changes in the treatment of hypertension, in the effectiveness of that treatment, and in mortality from cerebrovascular stroke in men and women in two counties in Finland. One of these counties was North Karelia, where a comprehensive cardiovascular programme based in the community had been launched in 1972. Cross sectional surveys in large representative samples of the middle aged populations were carried out in 1972, 1977, and 1982. Average annual mortality from stroke adjusted for age was calculated for the two year periods 1971-2, 1977-8, and 1980-1. The proportion of hypertensive men being effectively treated for their hypertension increased in both areas from 1972 to 1977 and further from 1977 to 1982. Mortality from stroke in middle aged men decreased in both areas during both observation periods. The proportion of hypertensive women being effectively treated greatly increased in both areas from 1972 to 1977. This was associated with a large decline in mortality from stroke. In North Karelia the proportion of women being effectively treated was remarkably high but decreased somewhat between 1977 and 1982; this decrease was associated with an increase in mortality from stroke in the women aged 35-64. These results support the idea that effective antihypertensive treatment in the community is a major determinant of mortality from stroke in both men and women.
A rapidly growing lung mass with air crescent formation
Authors: Harpreet K Lota, Michael Dusmet, Katrine Steele, Athol U Wells, Andrew G Nicholson, David M Hansell, Elisabetta A Renzoni
Journal: Thorax (2012)

A 58-year-old man who never smoked and was under follow-up for polymyositis associated with fibrotic interstitial lung disease was found to have an incidental opacity in the right upper lobe on a chest radiograph. He had been treated with daily azathioprine 200 mg and prednisolone 10 mg for 15 years. A CT chest revealed a mass-like lesion of relatively low attenuation suggesting necrosis (figure 1). Bronchoalveolar lavage was negative for microbiology and cytology. CT-guided biopsies were reported as showing necrosis and inflammation only. A month later, he developed cough with malodorous sputum, generalised fatigue, mild fevers, sweats and dyspnoea.



Figure 1 
Initial CT through the upper lobes showing an amorphous relatively low attenuation (near-fluid density) mass in the posterior segment of the right upper lobe. Sections through …
Israel restricts fertility treatment
Authors: B. J. Siegel-Itzkovich
Journal: BMJ (1999)

Israel's health ministry has used new medical guidelines, drawn up by a committee of 10 doctors, to limit access to in vitro fertilisation treatments guaranteed under the country's national health insurance law. From now on, infertile women over age 45 will not be able to undergo treatment with their own ova, and those over 51 won‘t be given donated ova.

Under the 1995 universal health insurance law, which provides a basket of health services to all residents, infertile women—whether married or single—are entitled …
Sinus Standstill Following Intravenous Lidocaine Administration
Authors: Tsung O. Cheng
Journal: JAMA (1973)

A fatal case of sinus standstill followed intravenous injection of therapeutic doses of lidocaine hydrochloride. The patient had congestive heart failure, but had no "sick sinus syndrome." To our knowledge, serious, adverse effects of lidocaine on sinus node function have not been reported previously. Our experience suggests that clinical assessment of the cardiac status is an important consideration in selecting a therapeutic dose of lidocaine. All patients receiving this drug require observation for adverse effects, even if doses are within the currently recommended ranges.
pH stability and activity curves of pepsin with special reference to their clinical importance.
Authors: D W Piper, B H Fenton
Journal: Gut (1965)

A study of the effect ofpH on the stability and activity of pepsin showed that 70 % of maximal peptic activity was still present at pH 4 5 and that pepsin was irreversibly inacti- vated at pH 8.The clinical implications of these findings are discussed.
Subjective effort derives from a neurological monitor of performance costs and physiological resources
Authors: Mattie Tops, Maarten A. S. Boksem, Sander L. Koole
Journal: Behavioral and Brain Sciences (2013)

Kurzban et al.'s expectancy-value mechanism of effort allocation seems relevant in situations when familiar tasks are initiated. However, we think additional mechanisms are important when people continue with a task for a prolonged time. These mechanisms, which are particularly relevant for performance of novel or urgent tasks, involve neural systems that track performance costs and resources.
Recommendations for treatment of lymphomatoid papulosis with methotrexate: a report from the Dutch Cutaneous Lymphoma Group
Authors: M.S. Bruijn, B. Horváth, P.C. van Voorst Vader, R. Willemze, M.H. Vermeer
Journal: British Journal of Dermatology (2015)

Journal Article Recommendations for treatment of lymphomatoid papulosis with methotrexate: a report from the Dutch Cutaneous Lymphoma Group Get access M.S. Bruijn, M.S. Bruijn Department of Dermatology University Medical Centre of Groningen Hanzeplein 1 9700 RB Groningen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar B. Horváth, B. Horváth Department of Dermatology University Medical Centre of Groningen Hanzeplein 1 9700 RB Groningen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.C. van Voorst Vader, P.C. van Voorst Vader Department of Dermatology University Medical Centre of Groningen Hanzeplein 1 9700 RB Groningen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar R. Willemze, R. Willemze Department of Dermatology Leiden University Medical Centre Leiden the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.H. Vermeer M.H. Vermeer Department of Dermatology Leiden University Medical Centre Leiden the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Pages 1319–1322, https://doi.org/10.1111/bjd.13920 Published: 01 November 2015
Trastuzumab-DM1: Building a Chemotherapy-Free Road in the Treatment of Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Steven J. Isakoff, José Baselga
Journal: Journal of Clinical Oncology (2010)

previously untreated acute myeloid leukemia. Blood 114:326, 2009 (abstr 790) 18. Borthakur G, Jabbour E, Wang X, et al: Effect of front-line therapy with fludarabine, cytarabine, filgrastim, and gemtuzumab ozogamicin (FLAG-GO) on outcome in core-binding factor associated acute myelogenous leukemia (CBFAML). J Clin Oncol 28:499s, 2010 (abstr 6552) 19. Lo-Coco F, Cimino G, Breccia M, et al: Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood 104:1995-1999, 2004 20. Estey EH, Giles FJ, Beran M, et al: Experience with gemtuzumab ozogamycin (“mylotarg”) and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood 99:4222-4224, 2002 21. Breccia M, Cimino G, Diverio D, et al: Sustained molecular remission after low dose gemtuzumab-ozogamicin in elderly patients with advanced acute promyelocytic leukemia. Haematologica 92:1273-1274, 2007 22. Ravandi F, Estey E, Jones D, et al: Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol 27:504-510, 2009 23. Vogel CL, Cobleigh MA, Tripathy D, et al: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719-726, 2002 24. Johnson JR, Cohen M, Sridhara R, et al: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res 11:6414-6421, 2005
β‐Adrenoceptor stimulation and neutrophil accumulation in mouse airways
Authors: M. Miyamoto, M. Tomaki, J. Lötvall, A. Lindén
Journal: European Respiratory Journal (2004)

This study characterised the effect of β‐adrenoceptor stimulation on endotoxin-induced accumulation of neutrophilic granulocytes in mouse airways, where the cytokines interleukin (IL)‐6 and macrophage inflammatory protein (MIP)‐2 are involved as mediators. The β 2 ‐adrenoceptor agonist salbutamol (0.025–250 fMol) was administered intranasally in mice 24 h prior to administration of endotoxin (10 µg) intranasally. Bronchoalveolar lavage (BAL) fluid and venous blood, respectively, was harvested (6 or 24 h) after administration of endotoxin. Salbutamol substantially decreased the number of neutrophils in BAL fluid from endotoxin-exposed (6 and 24 h) mice and this effect was dose dependent (24 h). Pretreatment with the β‐adrenoceptor antagonist propranolol attenuated the inhibitory effect of salbutamol on BAL neutrophils (6 and 24 h), an attenuation that was not due to any unspecific effect of propranolol. Salbutamol also substantially decreased IL‐6, but not MIP‐2 in BAL fluid (6 h). In contrast to BAL fluid, salbutamol caused a moderate increase in blood neutrophils (24 h). In conclusion, as indicated in mouse airways in vivo , β‐adrenoceptor stimulation prior to endotoxin exposure inhibits the induced accumulation of neutrophils at a time point much later than that anticipated from its bronchodilatory effect. Even though the detailed molecular mechanisms behind this sustained “anti-inflammatory” effect remain unknown, it seems likely that this effect is in part due to a decrease in the local concentration of interleukin‐6.
OP10 * ROLE OF C-MYC IN CHOROID PLEXUS TUMOURS
Authors: A. Merve, S. Acquati, S. Marino
Journal: Neuro-Oncology (2014)

INTRODUCTION: Choroid plexus tumours (CPT) are intracranial brain tumours, predominantly occurring in children. They are classified into three prognostically relevant histological categories - choroid plexus papillomas (CPP), atypical choroid plexus papillomas (ACPP) and choroid plexus carcinomas (CPC). c-Myc is a proto-oncogene deregulated in various malignancies, including paediatric brain tumours such as medulloblastoma and glioma. While modelling c-Myc-driven brain tumourigenesis in the mouse, we unexpectedly found a significant incidence of CPTs in transgenic mice overexpressing c-Myc in neural progenitor cells. Here, we set out to test the hypothesis that deregulation of c-Myc expression plays a role in human CPTs. METHOD: RosaMycIB12; Nestin Cre mice were generated and kept under tumour watch until symptomatic or termination of the experiment (20 months of age), when histological analysis was performed on their brains. 46 human CPT samples were obtained from the MRC UK Brain Archive Information Network (BRAIN UK) and tested for c-Myc overexpression and c-Myc amplification by immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH) respectively. RESULTS: CPT incidence in transgenic mice was 44% (18/41): 66% (12/18) CPP and 33% (6/18) CPC. No other tumour types were detected in these mice. No tumours were detected in the control cohort. Results of the on-going characterisation of c-Myc expression in the human tumours will be presented. CONCLUSION: Overexpression of c-Myc in neural progenitor cells leads to CPTs development in a proportion of the compound mutant mice. Translational analysis of the role of c-Myc in human CPTs will determine the validity of this model in mimicking the human tumours.