tbuckley/cabot-search huggingface dataset:
Cancer-Testis Genes Are Coordinately Expressed and Are Markers of Poor Outcome in Non–Small Cell Lung Cancer
Authors: Ali O. Gure, Ramon Chua, Barbara Williamson, Mithat Gonen, Cathy A. Ferrera, Sacha Gnjatic, Gerd Ritter, Andrew J.G. Simpson, Yao-T. Chen, Lloyd J. Old, Nasser K. Altorki
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancer-testis gene expression occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non–small cell lung cancer (NSCLC). Experimental Design: Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome. Results: At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1 and MAGE-A3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung. Conclusions: Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.
Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia
Authors: Lionel Flamant, Annick Notte, Noelle Ninane, Martine Raes, Carine Michiels
Journal: Molecular Cancer (2010)

Abstract Background Hypoxia is a hallmark of solid tumors and is associated with metastases, therapeutic resistance and poor patient survival. Results In this study, we showed that hypoxia protected MDA-MB-231 breast cancer cells against paclitaxel- but not epirubicin-induced apoptosis. The possible implication of HIF-1 and AP-1 in the hypoxia-induced anti-apoptotic pathway was investigated by the use of specific siRNA. Specific inhibition of the expression of these two transcription factors was shown to increase apoptosis induced by chemotherapeutic agents under hypoxia indicating an involvement of HIF-1 and AP-1 in the anti-apoptotic effect of hypoxia. After HIF-1 specific inhibition and using TaqMan Human Apoptosis Array, 8 potential HIF-1 target genes were identified which could take part in this protection. Furthermore, Mcl-1 was shown to be a potential AP-1 target gene which could also participate to the hypoxia-induced chemoresistance. Conclusions Altogether, these data highlight two mechanisms by which hypoxia could mediate its protective role via the activation of two transcription factors and, consecutively, changes in gene expression encoding different anti- and pro-apoptotic proteins.
GPs vote to end "disastrous" out of area scheme
Authors: G. Iacobucci
Journal: BMJ (2015)

GP leaders will have to seek an end to the government’s out of area practice registration scheme after local representatives passed a motion condemning the initiative as a “disaster.”

The motion, passed by local medical committees (LMCs) at their annual conference in London, said that the removal of geographical practice boundaries had fragmented the care of patients and called on the BMA’s General Practitioners Committee (GPC) to negotiate an end to the scheme.

The conference also backed a separate strand of the motion that condemned NHS England’s failure to provide a comprehensive home visiting service for patients who registered as “out of area” patients.

The scheme was piloted in specific parts of …
Vitronectin in liver disorders: Biochemical and immunohistochemical studies
Authors: Sadataka Inuzuka, Takato Ueno, Takuji Torimura, Seishu Tamaki, Ryuichiro Sakata, Michio Sata, Hiroshi Yoshida, Kyuichi Tanikawa
Journal: Hepatology (1992)

The concentration of plasma vitronectin was determined and compared with various parameters of liver function including the blood coagulation system in patients with liver diseases. The severity of cirrhosis was graded according to Child's criteria and compared with the plasma vitronectin level. Furthermore, the distribution of vitronectin in the liver of patients with liver diseases was studied by light and electron microscopy using the indirect immunoperoxidase method. The plasma vitronectin level was low in all liver disease groups as compared with the healthy controls. The difference from the controls was significant in patients with hepatocellular carcinoma and decompensated cirrhosis. Moreover, the plasma vitronectin level was positively correlated with the levels of serum cholinesterase, albumin, plasma α 2 plasmin inhibitor–plasmin complex and the prothrombin time and results of the hepatoplastin test. Plasma vitronectin decreased with increasing severity of cirrhosis according to Child's criteria. These results suggest that the plasma vitronectin level is a useful parameter of hepatic synthetic function in patients with liver diseases; it may also reflect the severity of cirrhosis. Light microscopy revealed vitronectin in the area of focal necrosis and the portal tracts in the liver of patients with acute viral hepatitis, in the area of piecemeal necrosis in the liver of patients with chronic hepatitis and along the area of fiber deposition in the liver of patients with cirrhosis. Immunoelectron microscopy showed vitronectin in the rough endoplasmic reticulum of hepatocytes. Moreover, vitronectin was seen around inflammatory cells, endothelial cells, Ito cells and hepatocytes in the perisinusoidal area near focal necrosis and piecemeal necrosis and on collagen fibers. These results suggest that vitronectin may be produced by hepatocytes and that they play an important role as an extracellular matrix component in the injured liver. (Hepatology 1992;15:629-636).
Immunoregulatory Function of Specific IgG I. Results in Nonatopic Subjects
Authors: J G Michael, I L Bernstein
Journal: Allergy (1978)

Nonatopic subjects immunized with short ragweed developed both reaginic IgE and blocking IgG antibodies to the antigen. Administration of 250 microgram-specific ragweed IgG antibodies 1 week before, simultaneously, or up to 2 weeks after start of immunization with ragweed extract abrogated the production of anti-ragweed reaginic antibodies which was measured by skin reactivity. Formation of specific ragweed IgG antibodies was unaffected by IgG treatment. These results indicate selective regulation of an immune response in humans by IgG.
Increased Oxidative DNA Damage in Mammary Tumor Cells by Continuous Epidermal Growth Factor Stimulation
Authors: J.-i. Hamada, D. Nakata, D. Nakae, Y. Kobayashi, H. Akai, Y. Konishi, F. Okada, T. Shibata, M. Hosokawa, T. Moriuchi
Journal: JNCI Journal of the National Cancer Institute (2001)

Growth factors can enhance the malignant potential of tumor cells. To examine the relationship between growth factors and tumor progression, we previously established a weakly malignant cell line, ER-1. We found that a 24-hour exposure of ER-1 cells to epidermal growth factor (EGF) induced malignant properties (tumor progression) that were reversible but that, after a 1-month exposure, these changes were irreversible. In this study, we investigated the irreversible changes induced in ER-1 cells by a 1-month exposure to EGF and the possible involvement of oxidative stress.ER-1 cells were treated with EGF (100 ng/mL) for 1 month in the presence or absence of an antioxidant, N-acetylcysteine or selenium, and compared with untreated control ER-1 cells. We assessed tumor progression by measuring intracellular peroxide levels, 8-hydroxydeoxyguanosine (a marker for oxidative DNA damage) levels, in vitro invasiveness, and in vivo tumorigenicity and metastatic ability. All statistical tests are two-sided.After ER-1 cells were treated for 1 month with EGF, levels of intracellular peroxide and 8-hydroxyguanosine in the DNA of treated cells were higher than those in the DNA of control cells, and treated ER-1 cells were more tumorigenic and metastatic in vivo and more invasive in vitro than untreated control cells (all P<.001). Levels of 8-hydroxyguanosine in DNA increased as the length of the EGF treatment increased (P<.001). However, when N-acetylcysteine or selenium was added with EGF for 1 month, levels of intracellular peroxide and 8-hydroxyguanosine in DNA were comparable to those in control cells (r =.795). Both tumorigenicity (P =.008) and metastatic ability (P<.001) decreased after addition of N-acetylcysteine or selenium.The irreversible changes caused by continuous EGF stimulation of ER-1 cells result from increased oxidative damage in the DNA, which generates tumor cells with more malignant characteristics.
Benefits and Adverse Events in Younger Versus Older Patients Receiving Adjuvant Chemotherapy for Colon Cancer: Findings From the Adjuvant Colon Cancer Endpoints Data Set
Authors: Joleen Hubbard, David M. Thomas, Greg Yothers, Erin Green, Charles Blanke, Michael J. O'Connell, Roberto Labianca, Qian Shi, Archie Bleyer, Aimery de Gramont, Daniel Sargent
Journal: Journal of Clinical Oncology (2012)

Limited data exist regarding the outcomes of adjuvant therapy in younger patients with stage II and III colon cancer. We examined disease-free survival (DFS), overall survival (OS), recurrence-free interval (RFI), and grade 3+ adverse events (AEs) in younger patients in the 33,574 patient Adjuvant Colon Cancer Endpoints Group data set.Individual patient data from 24 randomized phase III clinical trials were obtained for survival outcomes, which included 10 clinical trials for AE outcomes. Two age-based cutoff points were used to define younger patients: age younger than 40 years and younger than 50 years. Adjuvant therapy benefit analyses were limited to the nine clinical trials in which the investigational chemotherapeutic arm demonstrated benefit.One thousand seven hundred fifty-eight patients (5.2%) were younger than 40 years, 5,817 patients (17.3%) were younger than 50 years, and only 299 patients (0.9%) were younger than 30 years. No meaningful differences in sex or stage were noted in younger versus older patients. Younger and older patients did not differ in RFI (age, < 40 years: hazard ratio [HR], 1.0; P = .62 and age < 50 years: HR, 1.02; P = .35). Younger patients (both cutoff points), had longer OS and DFS than older patients. In trials demonstrating adjuvant therapy benefit, similar DFS benefit was observed by age. Younger patients experienced less leukopenia and stomatitis, but more frequent nausea/vomiting.Among patients on clinical trials, younger and older patients with stage II and III colon cancer had similar RFI and adjuvant therapy benefit. Younger patients have longer OS and DFS, which is likely primarily because of fewer competing causes of death. Adjuvant therapy is beneficial for colon cancer in patients younger than 50 years who meet typical clinical trial eligibility criteria.
Reconstitution of cultured intestinal epithelial monolayers with a mucosal-derived T lymphocyte cell line. Modulation of epithelial phenotype dependent on lymphocyte-basolateral membrane apposition.
Authors: P Kaoutzani, S P Colgan, K L Cepek, P G Burkard, S Carlson, C Delp-Archer, M B Brenner, J L Madara
Journal: Journal of Clinical Investigation (1994)

In vivo, epithelial cells which line the intestine are intimately associated with lymphocytes, termed intraepithelial lymphocytes. Previous studies have demonstrated that intraepithelial lymphocytes are present in the uninflamed mucosa, and become especially prominent in various human enteropathies including coeliac disease, tropical sprue, dermatitis herpetiformis, and giardiasis. Using the intestinal crypt cell line T84, and a previously well-defined human mucosa-derived lymphocyte (MDL) line with phenotypic features similar to (but not specific for) intraepithelial lymphocytes, we describe a co-culture model to study the functional sequellae of MDL-T84 cell interactions in vitro. A co-culture method was defined which permitted reconstitution of the paracellular spaces of physiologically confluent epithelial monolayers with MDL. Such co-cultures thus mimicked the correct geometry of intraepithelial lymphocytes-epithelial cell interactions. The presence of physiologically positioned MDL brought about specific and dramatic effects on intestinal epithelial monolayer function. In a dose-dependent fashion, the presence of MDL significantly attenuated barrier function (expressed as a decrease in monolayer resistance), decreased epithelial electrogenic Cl- secretion, and modulated epithelial-neutrophil interactions. Such effects were not reproduced in monolayers similarly reconstituted with inert polystyrene beads equivalent in size to MDL. These MDL-elicited effects on epithelial function specifically required direct MDL apposition to the epithelial basolateral membrane. Furthermore, this specific form of MDL-epithelial basolateral contact released soluble factors which were able to confer the MDL-reconstituted phenotype on virgin epithelial monolayers in the absence of MDL. We have previously shown that many aspects of the MDL converted epithelial phenotype described here can be induced by IFN-gamma. While IFN-gamma, a cytokine produced by many lymphocytes including intraepithelial lymphocytes, was detectable in conditioned supernatants from co-cultures, it existed at concentrations insufficient to fully explain the physiologic effects observed here.
Area deprivation predicts lung function independently of education and social class
Authors: S. Shohaimi, A. Welch, S. Bingham, R. Luben, N. Day, N. Wareham, K-T. Khaw
Journal: European Respiratory Journal (2004)

The cross-sectional association between socioeconomic status (at both the individual and area-based level) and lung function, as measured by forced expiratory volume in one second, in a large population-based cohort was investigated. The study population consisted of 22,675 males and females aged 39-79 yrs. They were recruited from the general community in Norfolk, UK using general practice age/sex registers, as part of the European Prospective Investigation into Cancer (EPIC-Norfolk). It was found that being in a manual occupational social class, having no educational qualifications and living in a deprived area all independently predicted significantly lower lung function, even after controlling for smoking habit. The influence of area-deprivation on lung function, independent of individual socioeconomic status and of individual smoking habit, suggests that apart from targeting individuals who are at high-risk, such as smokers, environmental determinants also need to be examined when considering measures to improve respiratory health.
Antenatal peer support workers and initiation of breast feeding: cluster randomised controlled trial
Authors: C. MacArthur, K. Jolly, L. Ingram, N. Freemantle, C.-L. Dennis, R. Hamburger, J. Brown, J. Chambers, K. Khan
Journal: BMJ (2009)

<b>Objective</b> To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. <b>Design</b> Cluster randomised controlled trial. <b>Setting</b> Community antenatal clinics in one primary care trust in a multiethnic, deprived population. <b>Participants</b> 66 antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were randomised to receive the peer support worker service and 33 clinics including 1371 women were randomised to receive standard care. <b>Intervention</b> An antenatal peer support worker service planned to comprise a minimum of two contacts with women to provide advice, information, and support from approximately 24 weeks' gestation within the antenatal clinic or at home. The trained peer support workers were of similar ethnic and sociodemographic backgrounds to their clinic population. <b>Main outcome measure</b> Initiation of breast feeding obtained from computerised maternity records of the hospitals where women from the primary care trust delivered. <b>Results</b> The sample was multiethnic, with only 9.4% of women being white British, and 70% were in the lowest 10th for deprivation. Most of the contacts with peer support workers took place in the antenatal clinics. Data on initiation of breast feeding were obtained for 2398 of 2511 (95.5%) women (1083/1140 intervention and 1315/1371 controls). The groups did not differ for initiation of breast feeding: 69.0% (747/1083) in the intervention group and 68.1% (896/1315) in the control groups; cluster adjusted odds ratio 1.11 (95% confidence interval 0.87 to 1.43). Ethnicity, parity, and mode of delivery independently predicted initiation of breast feeding, but randomisation to the peer support worker service did not. <b>Conclusion</b> A universal service for initiation of breast feeding using peer support workers provided within antenatal clinics serving a multiethnic, deprived population was ineffective in increasing initiation rates. <b>Trial registration</b> Current Controlled Trials ISRCTN16126175.
The Integration of Care for Mental Health, Substance Abuse, and Other Behavioral Health Conditions into Primary Care: Executive Summary of an American College of Physicians Position Paper
Authors: Ryan A. Crowley, Neil Kirschner
Journal: Annals of Internal Medicine (2015)

Behavioral health care includes care for patients around mental health and substance abuse conditions, health behavior change, life stresses and crises, and stress-related physical symptoms. Mental and substance use disorders alone are estimated to surpass all physical diseases as a major cause of worldwide disability by 2020. The literature recognizes the importance of the health care system effectively addressing behavioral health conditions. Recently, there has been a call for the use of the primary care delivery platform and the related patient-centered medical home model to effectively address these conditions. This position paper focuses on the issue of better integration of behavioral health into the primary care setting. It provides an environmental scan of the current state of conditions included in the concept of behavioral health and examines the arguments for and barriers to increased integration into primary care. It also examines various approaches of integrated care delivery and offers a series of policy recommendations that are based on the reviewed information and evidence to inform the actions of the American College of Physicians and its members regarding advocacy, research, and practice.
Effect of azithromycin on primary bronchial epithelial cells derived from stable lung allografts
Authors: D. M Murphy, I. A Forrest, C. Ward, P. A Corris, G. E Johnson, D. Jones, A. J Fisher, J. J Egan, T. E Cawston, J. L Lordan
Journal: Thorax (2007)

Obliterative bronchiolitis (OB), the main cause of lung allograft failure, is characterised by airway inflammation, neutrophilia, remodelling and fibrosis. Recent studies of the macrolide antibiotic azithromycin in OB, including one from our centre, have reported improved lung function with rescue therapy.1 The mechanism for this improvement remains unclear, but a recent study suggests that neutrophilic inflammation may be an important predictor of clinical response.2

Macrolides have anti-inflammatory properties in several pulmonary conditions. We hypothesised that the clinical benefit observed with azithromycin in patients undergoing lung transplantation may be related to the inhibition of factors key to airway neutrophilic inflammation, remodelling and fibrosis. The bronchial epithelium is in a pivotal …
Cancer Incidence and Survival Among American Indians Registered for Indian Health Service Care in Montana, 1982-1987
Authors: D. M. Bleed, D. R. Risser, S. Sperry, D. Hellhake, S. D. Helgerson
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Cancer Incidence and Survival Among American Indians Registered for Indian Health Service Care in Montana, 1982–1987 Get access Daniel M. Bleed, Daniel M. Bleed 1Billings Area Office, Indian Health Service, Billings, Mont., and Preventive Medicine Residency, The Johns Hopkins University School of Hygiene and Public HealthBaltimore, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar David R. Risser, David R. Risser * 2Chronic Disease Research Branch, Indian Health ServiceHeadquarters West, Albuquerque, N.M * Correspondence to: David R. Risser, Ph.D., M.P.H., Chronic Diseases Research Branch, Indian Health Service Headquarters West, 300 San Mateo, N.E., Ste. 500, Albuquerque, NM 87108 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sam Sperry, Sam Sperry 3Montana Department of Health and Environmental ServicesHelena, Mont Search for other works by this author on: Oxford Academic PubMed Google Scholar Debbie Hellhake, Debbie Hellhake 3Montana Department of Health and Environmental ServicesHelena, Mont Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven D. Helgerson Steven D. Helgerson 4Billings Area Office, Indian Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 19, 7 October 1992, Pages 1500–1505, https://doi.org/10.1093/jnci/84.19.1500 Published: 07 October 1992 Article history Received: 12 March 1992 Revision received: 02 June 1992 Accepted: 17 June 1992 Published: 07 October 1992
Comparison of airway immunopathology of eosinophilic bronchitis and asthma
Authors: C E Brightling
Journal: Thorax (2003)

<b>Background:</b> Eosinophilic bronchitis is a condition characterised by a corticosteroid responsive cough, sputum eosinophilia, and normal tests of variable airflow obstruction and airway responsiveness. We performed a detailed comparative immunopathological study to test the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma reflects differences in the nature of the lower airway inflammatory response. <b>Methods:</b> Exhaled nitric oxide was measured and induced sputum, bronchoscopy, bronchial wash (BW), bronchoalveolar lavage (BAL), and bronchial biopsy were performed in 16 subjects with eosinophilic bronchitis, 15 with asthma, and 14 normal controls. <b>Results:</b> Both eosinophilic bronchitis and asthma were characterised by an induced sputum, BW and BAL eosinophilia, an increased number of epithelial and subepithelial eosinophils, and increased reticular basement membrane thickness. The median concentration of exhaled nitric oxide was higher in those with eosinophilic bronchitis (12 ppb) or asthma (8.5 ppb) than normal controls (2 ppb) (95% CI of the difference 5 to 16, p&lt;0.0001 and 2 to 11.3, p=0.004, respectively). There were no group differences in epithelial integrity or the number of subepithelial T lymphocytes, mast cells or macrophages. <b>Conclusion:</b> With the exception of our previously reported association of smooth muscle mast cell infiltration with asthma, the immunopathology of eosinophilic bronchitis and asthma are similar which suggests that eosinophilic airway inflammation, increased exhaled nitric oxide, and increased basement membrane thickening are regulated independently of airway hyperresponsiveness.