tbuckley/cabot-search huggingface dataset:
Characterization of Spontaneous, Chemical, and Viral Transformants of a C3H/3T3-Type Mouse Cell Line by Transplantation Into Young Chick Blastoderms&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Mareel, L De Ridder, M De Brabander, L Vakaet
Journal: JNCI Journal of the National Cancer Institute (1975)

Cells from a C3H/3T3-type cell line were transplanted into defects of the lower layer of stage-4 chick blastoderms before and after “spontaneous,” chemical, and viral transformation. To check the validity of inhibition of lower-layer defect closure as a criterion of malignancy, we compared the behavior of the lower layer toward these cells with their in vitro growth pattern, their capacity to invade embryonic chick skin explants that were organotypically cultured, and their tumorigenicity in syngeneic mice. No false-positive results were observed with either test. The study of the in vitro growth pattern gave false-negative results during the early phase of spontaneous transformation, whereas these cells, exhibiting an untransformed growth pattern, were shown to be malignant by the other tests. We concluded that the inhibition of lower-layer defect closure is a reliable, sensitive, and rapid test for the detection of malignancy in tissuecultured cells from any source.
The D2 Dopamine Receptor Gene and Alcoholism: A Genetic Effect in the Liability for Alcoholism
Authors: C C H Cook, H M D Gurling
Journal: Journal of the Royal Society of Medicine (1994)

Three of five recent association studies have demonstrated an increased frequency of the A1 allele of the TaqI Restriction Fragment Length Polymorphism (RFLP) of the DRD2 locus in alcoholics compared to controls. One of three family studies has shown preliminary results in favour of linkage of this locus with alcoholism and heavy drinking. The possible mechanism of a genetic effect of the DRD2 locus in alcoholism remains open to speculation, but many involve personality characteristics such as impulsiveness or spontaneity. The applications of the findings of research in this field offer much potential for the prevention and treatment of alcoholism, but also raise certain ethical issues when applied to screening programmes. Future research will be assisted by the development of new, and more informative, genetic markers which are now available at this locus.
Impact of sedation and analgesia during noninvasive positive pressure ventilation on outcome: a marginal structural model causal analysis
Authors: Alfonso Muriel, Oscar Peñuelas, Fernando Frutos-Vivar, Alejandro C. Arroliga, Victor Abraira, Arnaud W. Thille, Laurent Brochard, Nicolás Nin, Andrew R. Davies, Pravin Amin, Bin Du, Konstantinos Raymondos, Fernando Rios, Damian A. Violi, Salvatore M. Maggiore, Marco Antonio Soares, Marco González, Fekri Abroug, Hans-Henrik Bülow, Javier Hurtado, Michael A. Kuiper, Rui P. Moreno, Amine Ali Zeggwagh, Asisclo J. Villagómez, Manuel Jibaja, Luis Soto, Gabriel D’Empaire, Dimitrios Matamis, Younsuck Koh, Antonio Anzueto, Niall D. Ferguson, Andrés Esteban
Journal: Intensive Care Medicine (2015)
Bcl11b is essential for group 2 innate lymphoid cell development
Authors: Jennifer A. Walker, Christopher J. Oliphant, Alexandros Englezakis, Yong Yu, Simon Clare, Hans-Reimer Rodewald, Gabrielle Belz, Pentao Liu, Padraic G. Fallon, Andrew N.J. McKenzie
Journal: The Journal of Experimental Medicine (2015)

Group 2 innate lymphoid cells (ILC2s) are often found associated with mucosal surfaces where they contribute to protective immunity, inappropriate allergic responses, and tissue repair. Although we know they develop from a common lymphoid progenitor in the bone marrow (BM), the specific lineage path and transcriptional regulators that are involved are only starting to emerge. After ILC2 gene expression analysis we investigated the role of Bcl11b, a factor previously linked to T cell commitment, in ILC2 development. Using combined Bcl11b-tom and Id2-gfp reporter mice, we show that Bcl11b is expressed in ILC2 precursors in the BM and maintained in mature ILC2s. In vivo deletion of Bcl11b, by conditional tamoxifen-induced depletion or by Bcl11b−/− fetal liver chimera reconstitution, demonstrates that ILC2s are wholly dependent on Bcl11b for their development. Notably, in the absence of Bcl11b there is a concomitant expansion of the RORγt+ ILC3 population, suggesting that Bcl11b may negatively regulate this lineage. Using Nippostrongylus brasiliensis infection, we reveal that the absence of Bcl11b leads to impaired worm expulsion, caused by a deficit in ILC2s, whereas Citrobacter rodentium infection is cleared efficiently. These data clearly establish Bcl11b as a new factor in the differentiation of ILC2s.
Socioeconomic status and cancer survival in Ontario.
Authors: W J Mackillop, J Zhang-Salomons, P A Groome, L Paszat, E Holowaty
Journal: Journal of Clinical Oncology (1997)

BACKGROUND AND PURPOSE It is known that the socioeconomic status (SES) of the patient is associated with cancer survival in the United States. The purpose of this study was to determine whether the association between SES and survival is also present in Canada, a society with a comprehensive, universal, health insurance program. METHODS A population-based cancer registry was used to identify the 357,530 cases of invasive cancer diagnosed in the Canadian province of Ontario between 1982 and 1991. Information from the 1986 Canadian census was linked to the registry and used to describe the SES of the area in which each patient resided. Cox regression was used to describe the association between median household income and survival while controlling for age, sex, and the region in which the patient resided. The Cox model was fitted in a competing risk framework to assess the association between income and the probability of specific causes of death. RESULTS Lung cancer and cancers of the head and neck region were relatively more common in poor-income communities, and cancers of the breast, CNS, and testis were relatively more common in richer communities. A strong and statistically significant association between community income and survival was observed in cancers of the head and neck region, cervix, uterus, breast, prostate, bladder, and esophagus. Smaller, but significant associations were seen in cancers of the lung and rectum. No significant association between community income and survival was observed in cancers of the stomach, colon, pancreas, or ovary. Analysis of the cause of death showed that community income is associated both with the probability of death from cancer and with the probability of death from other causes. CONCLUSION Although Canada's health care system was designed to provide equitable access to equivalent standards of care, it does not prevent a difference in cancer survival between rich and poor communities.
Prevalence of etravirine (ETR)-RAMs at NNRTI failure and predictors of resistance to ETR in a large Italian resistance database (ARCA)†
Authors: S. Rusconi, F. Adorni, B. Bruzzone, A. Di Biagio, G. Meini, A. Callegaro, G. Punzi, E. Boeri, M. Pecorari, L. Monno, N. Gianotti, L. Butini, L. Galli, E. Polilli, M. Galli
Journal: Clinical Microbiology and Infection (2013)
Surgery for pulmonary aspergilloma: A Moroccan center experience
Authors: Hicham Fenane, Khalid Bouti, Mehdi Maidi, A. Achir, D. Lamboni, M. Bouchikh, Y. Msougar, F. Ouchen, B. El Gajoui, M. Oyali, M. Caidi, A. Al Aziz, A. Benosman
Journal: European Respiratory Journal (2013)

The surgical treatment of pulmonary aspergilloma is challenging and controversial. The aim of our study is to evaluate the clinical spectrum pulmonary aspergilloma (PA) in our department. We undertook a retrospective study of 340 cases that were operated between January 1982 and December 2007. Medical records and treatment outcomes were reviewed. During the period of the study (25 years), we treated 350 patients: 247 males, and 103 females, with a sex ratio of 2.4, and a mean age of 38.3 years (extremes 7 and 73). 78% (n=274) of our group had a history of pulmonary tuberculosis. 9% had been treated twice. Thus, PA was principally developped in tuberculosis residual cavities. Hemoptysis was the main symptom. Bilateral PA was found in 2.6% of our cases. Surgical techniques are listed in table I.

View this table:

Surgical Techniques For Pulmonary Asperilloma





The postoperative morbidity was observed in 140 cases, table II lists these complications.

View this table:

Postoperative Complications of Pulmonary Aspergilloma Surgery





20 cases of postoperative mortality occured, 18 were observed after pneumonectmy. The average postoperative hospital stay was 16.8 days. The five-year actuarial survival rates was 85.6%. In our experience, mortality and morbidity rates were similar to literature. Surgery of PA could achieve satisfactory long-term outcomes.
Abstract 14095: Visceral Adipose Tissue and Cardiometabolic Risk Factors: Differences Between the Jackson Heart Study and the Framingham Heart Study
Authors: Jiankang Liu, Sean Coady, Udo Hoffmann, Herman A Taylor, Caroline S Fox
Journal: Circulation (2011)

Background - Despite higher levels of obesity and cardiovascular disease (CVD) risk, studies suggest that African Americans have lower levels of abdominal visceral adipose tissue (VAT) compared to ...
Selective reporting in trials of high risk cardiovascular devices: cross sectional comparison between premarket approval summaries and published reports
Authors: L. Chang, S. S. Dhruva, J. Chu, L. A. Bero, R. F. Redberg
Journal: BMJ (2015)

To investigate characteristics of clinical trials and results on safety and effectiveness reported in US Food and Drug Administration (FDA) documents for recently approved high risk cardiovascular devices compared with the characteristics and results reported in peer reviewed publications.A search of the publicly available FDA database was performed for all cardiovascular devices that received premarket approval from 1 January 2000 to 31 December 2010. For each study listed in the premarket approval documents, a Medline search was conducted to obtain the corresponding publication.Clinical trial characteristics, primary endpoints, and safety and efficacy results in the FDA documents and corresponding publications.106 cardiovascular devices received premarket approval from 1 January 2000 to 31 December 2010. FDA premarket approval documents for these devices contained 177 studies, of which 86 (49%) had been published by 1 January 2013. These 86 publications corresponded to 60 distinct devices. The mean time from FDA approval to publication in a peer reviewed journal was 6.5 months (range -4.8-7.5 years). In 22 (26%) of the 86 compared studies the number of participants enrolled in the study differed in the FDA summary and the corresponding publications. Of 152 primary endpoints identified in the FDA documents, in the corresponding publications three (2%) were labeled as secondary, 43 (28%) were unlabeled, and 15 (10%) were not found. Among the primary results, 69 (45%) were identical, 35 (23%) were similar, 17 (11%) were substantially different, and 31 (20%) could not be compared.Many clinical trials for high risk cardiovascular devices approved by the FDA remain unpublished. Even when trials are published, the study population, primary endpoints, and results can differ substantially from data submitted to the FDA.
EGFR, TS, and ERCC1 expression in penile squamous cancer (PSC).
Authors: T. B. Dorff, R. Schwartz, Y. Ma, J. Cai, A. Bulbul, E. C. Skinner, D. I. Quinn, K. Danenberg, A. Schuckman
Journal: Journal of Clinical Oncology (2011)

219 Background: PSC is an aggressive disease with devastating consequences. While near-universal EGFR overexpression has been documented, little is known about its clinical implications, and the potential role of KRAS mutations has not been described. In other tumor types, ERCC1 and TS expression are associated with response to platinum and 5FU chemotherapy, but have not yet been evaluated in PSC. Methods: After IRB approval, 28 PSC patients treated at LAC-USC were identified with tumor specimens available. Testing for EGFR, TS, and ERCC1 expression relative to internal standard gene was performed by real-time RT-PCR and correlated with clinical features. Results: The median age was 45 (30-78). There were 2 Black, 1 Asian, 1 White, and 15 Hispanic men; 9 had unspecified race. T stages included 4 Tis, 6 T1, 17 T2, and 9 T3; 11 men had lymph node (LN) involvement. No KRAS mutations were identified. EGFR had the highest relative expression (median 4.65, range 1.6-44.2), followed by TS (median 1.69, range 0.49-4.69); ERCC1 overexpression was rare (median 0.54, range 0.21-1.29). Higher EGFR expression was significantly associated with poor differentiation (median 12.5 compared to 3.6 for moderate/well differentiated tumors) on continuous (p=0.03 by Mann Whitney) and cut-point analysis using &gt;7 (two- sided p=0.03 by Fisher's exact test) but did not correlate with stage. Stage &gt; T2 showed a trend toward higher risk of LN involvement (p=0.06 by chi square). There was no correlation between differentiation and stage, and no significant correlation for ERCC1 or TS with grade or stage. Conclusions: EGFR overexpression is common in PSC and correlates with tumor grade but not stage, suggesting it may be important for disease progression. The absence of KRAS mutations may portend responsiveness to EGFR- targeted therapy based on experience in other tumors. Low ERCC1 as an association with platinum response will be explored in an expanded cohort. No significant financial relationships to disclose.
Phase I/II Trial of the Multidrug-Resistance Modulator Valspodar Combined With Cisplatin and Doxorubicin in Refractory Ovarian Cancer
Authors: Mark Baekelandt, Gustav Lehne, Claes G. Tropé, István Szántó, Per Pfeiffer, Bengt Gustavssson, Gunnar B. Kristensen
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the maximum-tolerated dose (MTD) of doxorubicin when given in combination with cisplatin and the multidrug-resistance (MDR) modulator valspodar and the remission rate induced by this combination in patients with platinum- and anthracycline-resistant ovarian cancer. PATIENTS AND METHODS: Fifty-nine patients who had failed prior platinum- and anthracycline-based chemotherapy were enrolled. During the dose-finding phase, patients received a loading dose of valspodar (1.5 or 2 mg/kg) via 2-hour intravenous (IV) infusion on day 1 and continuous IV infusion (CIVI) of valspodar (2, 4, or 10 mg/kg/d) over 3 days. Doxorubicin (starting from 20 up to 50 mg/m 2 ) and cisplatin (50 mg/m 2 ) were administered via 15- to 20-minute IV infusions on day 3. During the efficacy phase, patients received at least two treatment cycles unless toxicity was unacceptable, and responding patients and those with stable disease received four to six cycles. RESULTS: All patients completed at least one cycle of combined treatment. The MTD of doxorubicin was determined to be 35 mg/m 2 when administered with valspodar at 2 mg/kg loading dose and 10 mg/kg/d CIVI plus 50 mg/m 2 cisplatin. At these doses, valspodar blood concentrations known to reverse MDR in vitro were reached in all patients. Valspodar was well tolerated at all dose levels. Dose-limiting toxicities of the combination were primarily hematologic and included febrile neutropenia and prolonged leucopenia. The addition of valspodar to the treatment did not worsen cisplatin-related toxicity. Among 33 patients treated at the MTD for doxorubicin, one (3%) had a complete response, and four (12%) had a partial response. An additional seven patients experienced a stabilization of their previously progressive disease. The survival rates at 6 and 12 months were 59% and 19%, respectively. CONCLUSION: Valspodar can be safely coadministered with doxorubicin and cisplatin. Although the regimen used in this trial produced renewed responses in patients with heavily pretreated, refractory ovarian cancer, the value of valspodar in reversing resistance mediated by P-glycoprotein remains to be determined.
Inhibiting CXCR4/CXCL12 axis attenuates lung fibrosis both in vitro and in vivo
Authors: Fei Li, Huaping Dai, Jing Geng, Xuefeng Xu
Journal: European Respiratory Journal (2012)

Background: Lung fibrosis is characterized by fibroblast proliferation and collagen deposition. CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor 1 (SDF-1)/CXCL12, has been shown a critical role in cell proliferation. Here, we aim to examine the exact modulatory effects of CXCR4/CXCL12 on the fibroblast proliferation and lung fibrosis.

Methods: In vitro, primary human lung fibroblast (HLF) was isolated from patients with idiopathic pulmonary fibrosis and primary spontaneous pneumothorax for thoracoscopy with stapling of any air leak. CXCR4 protein level was assessed by indirect immunoblotting. MTT was used for the proliferation assay of bleomycin stimulated normal HLF in the presence or absence of AMD3100, an antagonist of CXCR4. In vivo, C57BL/6 mice were injected intraperitoneally with saline or AMD3100 (200ug) 1 day before intratracheal instillation of bleomycin (5mg/kg). Survival rate, lung fibrosis and pulmonary function will be assessed.

Results: The basal level of CXCR4 expression was higher on fibrotic HLF. Bleomycin could promote the proliferation of normal HLF, which could be significantly attenuated by AMD3100 pretreatment. AMD3100 administration significantly increased the survival rate of mice on day 21 compared with bleomycin treatment alone. According to the histology, pulmonary fibrosis was attenuated by AMD3100 pretreatment in later stage of bleomycin injury. However, no significant differences in total lung capacity and airway resistance were observed between these groups.

Conclusion: Collectively, our data suggest that AMD3100 could significantly attenuate lung fibrosis both in vitro and in vivo through inhibiting CXCR4/CXCL12 axis.
Prevalence and risk factors of co-morbidities in subjects with mild and moderate COPD detected by screening
Authors: Hans Van Remoortel, Miek Hornikx, Daniel Langer, Chris Burtin, Stephanie Everaerts, Peter Verhamme, Steven Boonen, Rik Gosselink, Marc Decramer, Thierry Troosters, Wim Janssens
Journal: European Respiratory Journal (2013)

Purpose:  There is little information about comorbidities and their risk factors in the preclinical stages of COPD. This study aims to investigate the prevalence of pre-morbid risk factors and co-morbid diseases and its association with daily physical activity in subjects detected with COPD by spirometry screening.   Methods:  Sixty subjects with mild to moderate COPD (63±6yrs, 68%male) were compared with 60 smoking controls (62±7yrs, 70%male) and 60 never-smoking controls (62±6yrs, 57%male). Comorbidities (cardiovascular, metabolic and musculoskeletal disease) and daily physical activity (SenseWear Armband) were measured objectively.   Results:  In subjects with COPD the prevalence of pre-morbid risk factors and co-morbid diseases was significantly higher compared to age-matched never-smokers, but was similar to smokers not suffering from COPD.  In COPD and smoking controls, the combination of cardiovascular and musculoskeletal disease was the most prevalent (15% and 12%, respectively). In a multivariate logistic regression analysis, physical inactivity and smoking, but not COPD, were found to be independent risk factors to predict ≥2 co-morbidities.   Conclusions:  Pre-morbid risk factors and co-morbid diseases are more prevalent in the preclinical stages of COPD and smokers without COPD. Physical inactivity and smoking but not airflow obstruction, appear as the main determinants for the presence of comorbidities.
Characteristics of the patiens diagnosed with pulmonary thromboembolism in the last 10 years
Authors: Rosa María Ortiz Comino, Rosalina De Los Santos López, Sindy Cedeño de Jesús
Journal: European Respiratory Journal (2013)

Introduction:  A study is made of the characteristics of pulmonary thromboembolism (PTE) in patients admitted to Virgen de las Nieves Hospital in Granada (Spain) between 2003 and 2012.  Materials and methods:  A retrospective descriptive study was made of patients diagnosed with PTE in our hospital between 2003 and 2102, analysing variables such as age, symptoms upon admission, diagnostic methods and known risk factors prior to diagnosis. The data were analysed using the SPSS.  Results:  363 patients were included, with a mean age of 65.3 years (63% over age 65 years). The main reason for consultation was dyspnea (74%) and chest pain (52%). D-dimer evaluation was always tested, being positive in 92%. Imaging tests for diagnostic confirmation comprised CT angiography (CTa) in 76% of the cases, scintigraphy in 31% or both in 7%. The analysis of the distribution over time shows that CTa was performed in 34.6% of the patients in 2003 against 94.6% of the patients in 2012. During hospital stay, Doppler-US evaluation for deep venous thrombosis (DVT) was made in 90% of the patients, in 56.2% was positive. In the 49% of the patients that had at least one risk factor, the most frequent was previous PTE or DVT (15%).  Conclusions:  PTE is more common in patients over 65 years of age. The most frequent clinical manifestation was dyspnea. The most commonly used imaging technique was CTa, with a significant increase in the last 10 years. A large percentage of patients had prior risk factors, and over half of them suffered concomitant DVT. The present study supports the importance of the clinical history and complementary test for the diagnosis of PTE, given the lack of specificity of the clinical manifestations.
Domiciliary investigation of sleep-related hypoxaemia in Duchenne muscular dystrophy
Authors: N Carroll, RJ Bain, PE Smith, S Saltissi, RH Edwards, PM Calverley
Journal: European Respiratory Journal (1991)

In Duchenne muscular dystrophy (DMD) nocturnal oxygen desaturation occurs during rapid eye movement (REM) sleep. Polysomnography, which requires hospital admission, will detect sleep-related breathing abnormalities. In order to avoid the inconvenience of hospital admission for the disabled patient, we investigated overnight oxygenation in ten boys with DMD by domiciliary oximetry. In four boys the results of oximetry were compared with those of a polysomnographic recording. The "repeatability" of domiciliary oximetry was assessed in six boys by performing oximetry on two non-consecutive nights. Older boys with DMD may develop a cardiomyopathy. In order to assess cardiac rhythm and ST segment changes we performed simultaneous Holter monitoring and oximetry in seven boys with overnight hypoxaemia. Six of the initial ten boys studied demonstrated episodic nocturnal hypoxaemia and there was a strong correlation between minimum oxygen saturation overnight and daytime arterial oxygen and carbon dioxide tensions (PaO2 r = 0.89; PaCO2 r = -0.87). Despite adequate REM time during polysomnography, greater oxygen desaturation was found during domiciliary oximetry. No difference was found in the severity of desaturation recorded in the boys who were studied on two separate occasions. Five boys demonstrated marked heart rate variation during hypoxaemic episodes and more serious arrhythmias occurred overnight in the three most hypoxaemic boys. Domiciliary oximetry is a simple, repeatable method of assessing overnight oxygenation and compares well with polysomnography. In boys with advanced DMD and severe nocturnal hypoxaemia, 24 h electrocardiographic monitoring may detect potentially life-threatening arrhythmias.