tbuckley/cabot-search huggingface dataset:
A systematic review of lung-sparing extirpative surgery for pleural mesothelioma
Authors: Elaine Teh, Francesca Fiorentino, Carol Tan, Tom Treasure
Journal: Journal of the Royal Society of Medicine (2011)

Summary Objectives There is a resurgence of interest in lung-sparing extirpative surgery for malignant pleural mesothelioma with recent reports of better survival and fewer adverse consequences than with extrapleural pneumonectomy. However, these operations are not well-characterized and to offer evidence-based clinical recommendations and to plan future trials a summary of what is already known is required. Design A formal literature search was performed and all recovered titles were sequentially sifted by title, abstract and full-text reading according to prespecified criteria. Papers were selected if they contained data relevant to the area of enquiry. Quantitative synthesis and textual analysis, appropriate to the material, were performed. Setting Follow-up studies of patients undergoing surgery for malignant pleural mesothelioma in specialist thoracic or cardiothoracic units. Participants Among the operated patients described in these papers, a total of 1270 patients had undergone lung-sparing surgery for mesothelioma. Results There were no randomized trials or other forms of controlled studies. From 464 titles, 26 papers contained sufficient data on 1270 patients to be included in the systematic review. Operative descriptions for all series were extracted and tabulated and variation was found in the nature of surgery within and between series, and the degree of detail with which it was described. There was more operative detail in recent papers. All available numerical data were extracted, tabulated and summarized using quantitative methods. The average survival at 1, 2, 3, 4 and 5 years was 51%, 26%, 16%, 11% and 9%, respectively. There were no data on patients’ performance status, symptomatic change, or other patient reported outcomes. Conclusions In the absence of any form of control data, no conclusions can be drawn concerning survival differences or symptomatic benefits attributable to surgery. As mesothelioma surgery is restricted to a selected minority of patients who often have multiple therapies, future research will require controlled studies with explicit definitions of the clinical and surgical intent.
Fractionated <sup>90</sup>Y-Ibritumomab Tiuxetan Radioimmunotherapy As an Initial Therapy of Follicular Lymphoma: An International Phase II Study in Patients Requiring Treatment According to GELF/BNLI Criteria
Authors: Tim M. Illidge, Sam Mayes, Ruth Pettengell, Andrew T. Bates, Mike Bayne, John A. Radford, W. David J. Ryder, Steven Le Gouill, Fabrice Jardin, Jill Tipping, Maureen Zivanovic, Françoise Kraeber-Bodere, Manuel Bardies, Caroline Bodet-Milin, Emmanuel Malek, Damien Huglo, Franck Morschhauser
Journal: Journal of Clinical Oncology (2013)

We report an international, multicenter phase II trial to evaluate the efficacy and toxicity of fractionated (90)Y-ibritumomab tiuxetan ((90)Y-IT) as initial therapy of follicular lymphoma (FL).A total of 74 patients, with a median age of 61 years (range, 28 to 80 years), were recruited requiring initial therapy by Groupe d'Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78% had stage III-IV disease, 32% intermediate, and 44% high-risk (according to FL International Prognostic Index). Treatment consisted of two doses of (90)Y-IT (11.1 MBq/kg) administered 8 to 12 weeks apart. Patients with more than 20% lymphoma infiltration of bone marrow (BM) received one infusion per week for 4 consecutive weeks of rituximab (375 mg/m(2)) and proceeded to fractionated radioimmunotherapy (RIT) only if a repeat BM biopsy demonstrated clearing of lymphoma to less than 20% involvement. The primary end point was end of treatment response of the intention-to-treat population. Secondary objectives were safety and progression-free survival (PFS).Initial overall response rate (ORR) was 94.4% (68 of 72 patients) with combined complete response (CR/CRu) of 58.3% (42 of 72 patients). Nine patients subsequently improved response making an ORR of 95.8% (69 of 72 patients) and CR/CRu of 69.4% (50 of 72 patients). At a median follow-up of 3.1 years (range, 0.2 to 5.2 years) estimated 3-year PFS is 58%, treatment-free survival 66%, and overall survival 95%. Median PFS is 40.2 months. Thirty patients have experienced disease progression and 24 have required further treatment. The treatment was well tolerated with few (2.8%) grade 3 or 4 infectious episodes or adverse events and manageable hematologic toxicity.Fractionated RIT using (90)Y-IT is an effective initial treatment for advanced-stage FL in patients with higher tumor burden requiring treatment.
Effect of pH Change upon Systemic Large and Small Vessel Resistance
Authors: MALCOLM FLEISHMAN, JERRY SCOTT, FRANCIS J. HADDY
Journal: Circulation Research (1957)

In the dog foreleg acute increase and decrease of hydrogen ion concentration is associated with active small vessel dilatation and constriction, respectively, through some direct effect upon vascular smooth muscle. These small vessel resistance changes do not affect total resistance in the intact leg because of directionally opposite active changes in artery resistance. The latter response appears to be related to central nervous connections and perhaps to circulating or locally released epinephrine, norepinephrine or unknown vasoactive substances.
Oxidative metabolism enables <i>Salmonella</i> evasion of the NLRP3 inflammasome
Authors: Meghan A. Wynosky-Dolfi, Annelise G. Snyder, Naomi H. Philip, Patrick J. Doonan, Maya C. Poffenberger, Daina Avizonis, Erin E. Zwack, Amber M. Riblett, Baofeng Hu, Till Strowig, Richard A. Flavell, Russell G. Jones, Bruce D. Freedman, Igor E. Brodsky
Journal: The Journal of Experimental Medicine (2014)

Microbial infection triggers assembly of inflammasome complexes that promote caspase-1–dependent antimicrobial responses. Inflammasome assembly is mediated by members of the nucleotide binding domain leucine-rich repeat (NLR) protein family that respond to cytosolic bacterial products or disruption of cellular processes. Flagellin injected into host cells by invading Salmonella induces inflammasome activation through NLRC4, whereas NLRP3 is required for inflammasome activation in response to multiple stimuli, including microbial infection, tissue damage, and metabolic dysregulation, through mechanisms that remain poorly understood. During systemic infection, Salmonella avoids NLRC4 inflammasome activation by down-regulating flagellin expression. Macrophages exhibit delayed NLRP3 inflammasome activation after Salmonella infection, suggesting that Salmonella may evade or prevent the rapid activation of the NLRP3 inflammasome. We therefore screened a Salmonella Typhimurium transposon library to identify bacterial factors that limit NLRP3 inflammasome activation. Surprisingly, absence of the Salmonella TCA enzyme aconitase induced rapid NLRP3 inflammasome activation. This inflammasome activation correlated with elevated levels of bacterial citrate, and required mitochondrial reactive oxygen species and bacterial citrate synthase. Importantly, Salmonella lacking aconitase displayed NLRP3- and caspase-1/11–dependent attenuation of virulence, and induced elevated serum IL-18 in wild-type mice. Together, our data link Salmonella genes controlling oxidative metabolism to inflammasome activation and suggest that NLRP3 inflammasome evasion promotes systemic Salmonella virulence.
Targeted Therapy for <i>BRAFV600E</i> Malignant Astrocytoma
Authors: Theodore P. Nicolaides, Huifang Li, David A. Solomon, Sujatmi Hariono, Rintaro Hashizume, Krister Barkovich, Suzanne J. Baker, Barbara S. Paugh, Chris Jones, Tim Forshew, Guy F. Hindley, J. Graeme Hodgson, Jung-Sik Kim, David H. Rowitch, William A. Weiss, Todd A. Waldman, C. David James
Journal: Clinical Cancer Research (2011)

Malignant astrocytomas (MA) are aggressive central nervous system tumors with poor prognosis. Activating mutation of BRAF (BRAF(V600E)) has been reported in a subset of these tumors, especially in children. We have investigated the incidence of BRAF(V600E) in additional pediatric patient cohorts and examined the effects of BRAF blockade in preclinical models of BRAF(V600E) and wild-type BRAF MA.BRAF(V600E) mutation status was examined in two pediatric MA patient cohorts. For functional studies, BRAF(V600E) MA cell lines were used to investigate the effects of BRAF shRNA knockdown in vitro, and to investigate BRAF pharmacologic inhibition in vitro and in vivo.BRAF(V600E) mutations were identified in 11 and 10% of MAs from two distinct series of tumors (six of 58 cases total). BRAF was expressed in all MA cell lines examined, among which BRAF(V600E) was identified in four instances. Using the BRAF(V600E)-specific inhibitor PLX4720, pharmacologic blockade of BRAF revealed preferential antiproliferative activity against BRAF(V600E) mutant cells in vitro, in contrast to the use of shRNA-mediated knockdown of BRAF, which inhibited cell growth of glioma cell lines regardless of BRAF mutation status. Using orthotopic MA xenografts, we show that PLX4720 treatment decreases tumor growth and increases overall survival in mice-bearing BRAF(V600E) mutant xenografts, while being ineffective, and possibly tumor promoting, against xenografts with wild-type BRAF.Our results indicate a 10% incidence of activating BRAF(V600E) among pediatric MAs. With regard to implications for therapy, our results support evaluation of BRAF(V600E)-specific inhibitors for treating BRAF(V600E) MA patients.
Extended atrial conduction system characterised by the expression of the HCN4 channel and connexin45
Authors: M YAMAMOTO, H DOBRZYNSKI, J TELLEZ, R NIWA, R BILLETER, H HONJO, I KODAMA, M BOYETT
Journal: Cardiovascular Research (2006)

Objective: In the heart, there are multiple supraventricular pacemakers involved in normal pacemaking as well as arrhythmias and the objective was to determine the distribution of HCN4 (major isoform underlying the pacemaker current, If) in the atria.
Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats
Authors: DaLiao Xiao, Chiranjib Dasgupta, Man Chen, Kangling Zhang, John Buchholz, Zhice Xu, Lubo Zhang
Journal: Cardiovascular Research (2013)

The mechanisms of heart failure remain largely elusive.The present study determined a causative role of DNA methylation in norepinephrine-induced heart hypertrophy and reduced cardiac contractility. Methods and resultsMale adult rats were subjected to norepinephrine infusion for 28 days, some of which were treated with 5-aza-2 ′deoxycytidine for the last 6 days of norepinephrine treatment.At the end of the treatment, hearts were isolated and left ventricular morphology and function as well as molecular assessments was determined.Animals receiving chronic norepinephrine infusion showed a sustained increase in blood pressure, heightened global genomic DNA methylation and changes in the expression of subsets of proteins in the left ventricle, left ventricular hypertrophy, and impaired contractility with an increase in the susceptibility to ischaemic injury.Treatment of animals with 5-aza-2 ′ -deoxycytidine for the last 6 days of norepinephrine infusion reversed norepinephrine-induced hypermethylation, corrected protein expression patterns, and rescued the phenotype of heart hypertrophy and failure. ConclusionsThe findings provide novel evidence of a causative role of increased DNA methylation in programming of heart hypertrophy and reduced cardiac contractility, and suggest potential therapeutic targets of demethylation in the treatment of failing heart and ischaemic heart disease.
The Po River Delta Respiratory Epidemiological Survey: an analysis of factors related to level of total serum IgE
Authors: T Sapigni, P Biavati, M Simoni, G Viegi, S Baldacci, L Carrozzi, P Modena, M Pedreschi, M Vellutini, P Paoletti
Journal: European Respiratory Journal (1998)

The purpose of the present study was to analyse whether sex, age, skin test reactivity, cigarette smoking and occupational exposure were related to the total serum immunoglobulin (Ig)E concentrations (kU x L[-1]), in a general population sample. We studied 1,905 subjects (915 males, 990 females) of a general population sample (n=2,841, 8-73 yrs) participating in the second cross-sectional respiratory epidemiological survey in the rural Po Delta area (near Venice, North Italy). Distribution of total serum IgE concentrations was skewed, thus a log-transformation was performed to obtain a Gaussian shape. Significantly higher values of IgE were found in males compared to females. In general, a peak of IgE concentration was found at 8-14 yrs. IgE values tended to be lower in older than younger adults. Significantly higher serum IgE levels were shown in subjects with a positive skin-prick test index (ST+) than in those with a negative skin-prick test index (ST-). There was a significant relationship of total IgE levels with skin reactivity to pollens and house-dust mites. In both sexes higher values of IgE were found in current smokers than in ex-nonsmokers, regardless of skin-test reactivity. There was no significant difference in IgE values between ex- and nonsmokers. Passive smoking and occupational exposure were significantly related to increased IgE values. Our results confirm that in a general population sample immunoglobulin E concentrations are related not only to skin-prick test reactivity to common aeroallergens, but also to other risk factors for chronic obstructive lung diseases, such as sex, active/ passive smoking and occupational exposure.
Non-endothelial cell endothelin-B receptors limit neointima formation following vascular injury
Authors: N. S. Kirkby, K. M. Duthie, E. Miller, Y. V. Kotelevtsev, A. J. Bagnall, D. J. Webb, P. W. F. Hadoke
Journal: Cardiovascular Research (2012)

The potent vasoconstrictor endothelin-1 (ET-1), acting on the endothelin-A (ETA) receptor, promotes intimal lesion formation following vascular injury. The endothelin-B (ETB) receptor, which mediates nitric oxide release and ET-1 clearance in endothelial cells, may moderate lesion formation, but this is less clear. We used selective ET receptor antagonists and cell-specific deletion to address the hypothesis that ETB receptors in the endothelium inhibit lesion formation following arterial injury. Neointimal proliferation was induced by wire or ligation injury to the femoral artery in mice treated with selective ETA (ABT-627) and/or ETB antagonists (A192621). Measurement of lesion formation by optical projection tomography and histology indicated that ETA blockade reduced lesion burden in both models. Although ETB blockade had little effect on ligation injury-induced lesion formation, after wire injury, blockade of the ETB receptor increased lesion burden (184% of vehicle; P < 0.05) and reversed the protective effects of an ETA antagonist. Selective deletion of ETB receptors from the endothelium, however, had no effect on neointimal lesion size. These results are consistent with ETB receptor activation playing an important role in limiting neointimal lesion formation following acute vascular injury, but indicate that this protective effect is not mediated by those ETB receptors expressed by endothelial cells. These data support the proposal that selective ETA antagonists may be preferable to mixed ETA/ETB antagonists for targeting the arterial response to injury.
Hepatocellular Carcinoma: From Gene to Public Health
Authors: R. Montesano, P. Hainaut, C. P. Wild
Journal: JNCI Journal of the National Cancer Institute (1997)

Liver diseases associated with chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma, account for more than 1 million deaths annually worldwide. In addition to HBV infection, other risk factors are involved in the etiology of hepatocellular carcinoma and, among these, dietary exposure to the carcinogenic aflatoxins is of particular importance in certain regions of southeast Asia and sub- Saharan Africa. The relative contributions of these two risk factors and the mechanism of the interaction between them in the pathogenesis of hepatocellular carcinoma are still poorly understood. The recently developed individual biochemical and molecular markers of aflatoxin exposure, i.e., aflatoxin-albumin adducts in blood and a specific GC to TA transversion mutation in codon 249 of the p53 gene (249 ser p53 mutation) in hepatocellular carcinomas, permit a better quantitative estimation of aflatoxin exposure in different populations of the world. A comprehensive summary of the data from our laboratory and the literature, based on a large number (>1000) of individual cases of hepatocellular carcinoma, is presented here and shows the following: 1) A high level and high prevalence of exposure to aflatoxins occur in West Africa, Mozambique, and some regions of China; 2) a high prevalence of the 249 ser p53 mutation is detected in these countries; and 3) hepatocellular carcinomas from countries with low or no exposure to aflatoxins show a very low prevalence of the 249 ser p53 mutation and distinctly different p53 mutation spectra, probably indicating different etiologies. Experimental and epidemiologic studies demonstrate an interaction between HBV infection and aflatoxins in hepatocarcinogenesis. The relevance of the biochemical/ molecular markers of aflatoxin exposure, HBV vaccination, and the reduction of aflatoxin exposure, in addition to the interaction between HBV infection and other risk factors in liver carcinogenesis, are discussed with regard to the implementation of measures for primary prevention.
Elastin biosynthesis: The missing link in tissue-engineered blood vessels
Authors: A PATEL, B FINE, M SANDIG, K MEQUANINT
Journal: Cardiovascular Research (2006)

Nearly 20years have passed since Weinberg and Bell attempted to make the first tissue-engineered blood vessels. Following this early attempt, vascular tissue engineering has emerged as one of the most promising approaches to fabricate orderly and mechanically competent vascular substitutes. In elastic and muscular arteries, elastin is a critical structural and regulatory matrix protein and plays an important and dominant role by conferring elasticity to the vessel wall. Elastin also regulates vascular smooth muscle cells activity and phenotype. Despite the great promise that tissue-engineered blood vessels have to offer, little research in the last two decades has addressed the importance of elastin incorporation into these vessels. Although cardiovascular tissue engineering has been reviewed in the past, very little attention has been given to elastin. Thus, this review focuses on the recent advances made towards elastogenesis and the challenges we face in the quest for appropriate functional vascular substitutes.
The role of polypositional CT in detecting adhesive process in the pleural cavity of TB patients under artificial pneumothorax (AP)
Authors: Rasul Amansakhedov, Andrei Perfiliev, Atadjan Ergeshov, Olga Demikhova
Journal: European Respiratory Journal (2012)

We studied 54 patients with different forms of destructive pulmonary TB, which received artificial pneumothorax (AP) during 5.5 (±1,5) months. Out of them 54.8% had infiltrative, 24.0% cavitary, 16.2% fibrocavitary, and 4.8% disseminated pulmonary TB. Sputum positive TB was established in 83.6% cases. Adhesive process in the pleural cavity was detected using polypositional computed tomography (CT). We developed the algorithm for radiographic monitoring of AP and detecting adhesive process in the pleural cavity. We established pleural adhesion in 70.3% cases; thoracocaustic was performed in 52.6% cases, with 100.0% effectiveness of AP. In 47.4% cases thoracocaustic was not administered to the patients with adhesive process; out of them 55.5% had effective AP, 16.6% – partially effective AP, and 27.9% – ineffective AP. Thus, polypositional CT demonstrated effectiveness in detecting adhesive process in the pleural cavity of TB patients.
Analysis of Glasgow Prognostic Score(GPS) in KRAS EXON2 Wild Type Patients with Metastatic Colorectal Cancer (MCRC) Treated with Salvage-Line Cetuximab-Based Regimen: HGCSG0901
Authors: Yuki Satoshi, Komatsu Yoshito, Harada Kazuaki, Fukushima Hiraku, Sasaki Takahide, Kobayashi Yoshimitsu, Tsuji Yasushi, Naruse Hirohito, Okuda Hiroyuki, Takahashi Yasuo, Hosokawa Ayumu, Konno Jun, Eto Kazunori, Kudo Mineo, Kawamoto Yasuyuki, Sonoda Norikazu, Sato Yasushi, Uebayashi Minoru, Kato Takashi, Onodera Manabu, Ohta Tomoyuki, Sakata Yuh
Journal: Annals of Oncology (2014)
Quality of life in Dutch women with lichen sclerosus
Authors: C.A. Lansdorp, K.E. van den Hondel, I.J. Korfage, M.J. van Gestel, W.I. van der Meijden
Journal: British Journal of Dermatology (2012)

Lichen sclerosus (LS) is a chronic inflammatory skin disease. Earlier studies have shown an impaired health-related quality of life (HRQoL), but more extensive research including generic questionnaires has not been reported.To investigate, in a cross-sectional study, the HRQoL of a sample of Dutch women with LS; to compare the resulting HRQoL data with that available from other skin diseases and the general Dutch population; to explore factors that may influence the HRQoL.Female members of the Dutch LS Foundation and Support Group filled out three questionnaires electronically: the Skindex-29, the SF-12 and the EQ-5D visual analogue scale (VAS). We distinguished Skindex-29 scores into groups with 'little' (score 0-24), 'mild' (25-31), 'moderate' (32-43) and 'severe' (44-100) impact on HRQoL. We compared differences using the Mann-Whitney U-test and the Kruskal-Wallis test, and correlations using Spearman's rank correlation coefficient.A total of 262 women with LS were included. The average diagnostic delay was 4·9 (SD 7·1) years. Patients had a mean total Skindex-29 score of 38·4 (0-100, SD 17·2). Domain scores for symptoms, emotions and functioning were 46·8 (SD 19·0), 38·2 (SD 20·2) and 33·6 (SD 19·3), respectively. The SF-12 showed average PCS-12 (physical component) and MCS-12 (mental component) scores of 47·7 and 48·5, respectively. For the Dutch population these scores were 49·3 and 52·3. The mean EQ-5D VAS score was 74·1 (SD 15·4).There is a considerable delay in diagnosis for female Dutch patients with LS. The Skindex-29 domain scores showed a moderately impaired HRQoL. Women with LS reported a lower generic HRQoL than the average female Dutch population.