tbuckley/cabot-search huggingface dataset:
DNA Repair Capacity of Lymphoblastoid Cell Lines From Sisters Discordant for Breast Cancer
Authors: D. O. Kennedy, M. Agrawal, J. Shen, M. B. Terry, F. F. Zhang, R. T. Senie, G. Motykiewicz, R. M. Santella
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Interindividual differences in DNA repair capacity may influence cancer risk. We tested whether the nucleotide excision repair pathway was deficient in breast cancer case patients by analyzing sister pairs. Methods: Cell lines derived from sisters discordant for breast cancer (137 families containing 158 case patients and 154 control sisters) were obtained from the Metropolitan New York Registry of Breast Cancer Families. Lymphoblastoid cells were treated with benzo[ a ]pyrene diolepoxide (BPDE) for 30 minutes and were either harvested immediately or were washed and cultured in complete medium for 4 hours to allow DNA repair. Immunofluorescence using a polyclonal anti-BPDE–DNA primary antibody was used to quantify BPDE–DNA adducts. Percent DNA repair capacity was calculated from the difference between staining immediately after treatment minus that after 4 hours of repair, divided by the initial damage and was categorized into quartiles based on control values. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for age at blood donation, body mass index, and smoking. Statistical tests were two-sided. Results: Mean percent DNA repair capacity was lower in breast cancer case patients than in control subjects (difference = 8.6, 95% CI = 4.3 to 13.8, P = .001). Using the quartile with the highest percent DNA repair capacity as the referent group, adjusted odds ratios of breast cancer increased from 1.23 (95% CI = 0.57 to 2.65) to 2.38 (95% CI = 1.17 to 4.86) to 2.99 (95% CI = 1.45 to 6.17) ( Ptrend = .002) as DNA repair capacity decreased. Conclusions: Deficient DNA repair capacity is associated with increased breast cancer risk.
Advanced Glycation End-Products Induce Tubular CTGF via TGF-β–Independent Smad3 Signaling
Authors: Arthur C.K. Chung, Haiyan Zhang, Yao-Zhong Kong, Jia-Ju Tan, Xiao R. Huang, Jeffrey B. Kopp, Hui Y. Lan
Journal: Journal of the American Society of Nephrology (2009)

Advanced glycation end-products (AGEs) can induce expression of connective tissue growth factor (CTGF), which seems to promote the development of diabetic nephropathy, but the exact signaling mechanisms that mediate this induction are unknown. Here, AGEs induced CTGF expression in tubular epithelial cells (TECs) that either lacked the TGF-beta1 gene or expressed dominant TGF-beta receptor II, demonstrating independence of TGF-beta. Furthermore, conditional knockout of the gene encoding TGF-beta receptor II from the kidney did not prevent AGE-induced renal expression of CTGF and collagen I. More specific, AGEs induced CTGF expression via the receptor for AGEs-extracellular signal-regulated kinase (RAGE-ERK)/p38 mitogen-activated protein kinase-Smad cross-talk pathway because inhibition of this pathway by several methods (anti-RAGE antibody, specific inhibitors, or dominant negative adenovirus to ERK1/2 and p38) blocked this induction. Overexpressing Smad7 abolished AGE-induced Smad3 phosphorylation and CTGF expression, demonstrating the necessity for activation of Smad signaling in this process. More important, knockdown of either Smad3 or Smad2 demonstrated that Smad3 but not Smad2 is essential for CTGF induction in response to AGEs. In conclusion, AGEs induce tubular CTGF expression via the TGF-beta-independent RAGE-ERK/p38-Smad3 cross-talk pathway. These data suggest that overexpression of Smad7 or targeting Smad3 may have therapeutic potential for diabetic nephropathy.
C reactive protein and obstructive sleep apnea in obese patients
Authors: Alessandro Di Marco Berardino, Anna Filomena Ferravante, Esmeralda Capristo, Luca Viglietta, Salvatore Valente, Flaminio Mormile
Journal: European Respiratory Journal (2014)

INTRODUCTION The activation of inflammatory mechanisms in obstructive sleep apnea (OSAS) as a possible explanation of the increased cardiovascular risk has been repeatedly suggested by the detection of increased levels of biomarkers such as TNF alpha, selectins, adhesion proteins, interleukins, and particularly the C-reactive protein (CRP).  AIMS AND METHODS We investigated the relationship among CRP, clinical and laboratory data and nocturnal cardiorespiratory monitoring parameters in a group of obese patients (42F, 44M mean BMI 43,9) submitted for suspected, never treated OSA, aged from 20 to 68 years (mean 44,3).  RESULTS Mild, moderate and severe OSA syndrome was diagnosed in 20, 24 and 46% of patients.  Greater values of AHI, ODI, creatinine, hemoglobin and lower HDL cholesterol levels were detected in men compared with women, with similar age and BMI.  CRP was greater in women(9.86+5.6 vs 6.66+3.6, p 0.016). Its levels were significantly associated with larger values of BMI (r 0.34, p 0.011) and lower of creatinine (r -0.26, p 0.05). Only the correlation with BMI was independent from other covariates. No significant correlation was detected between CRP and age or OSAS parameters. Only among women RCP positively correlated with serum glucose (r 0.49 p 0.023), insulin (r 0.43, p 0.048), and C peptide (r 0.59, p 0.004). Only among men, a small significant increase of CRP was found in the upper versus lowest AHI quartile (7.6 vs 7.1, p 0.042).  CONCLUSION Our data do not support the presence of a strong link between CRP levels and the presence and severity of OSA in obese patients. CRP appears mostly linked to obesity and, in the obese female, to glucose metabolism.
BMA polls GPs on extended hours and private provision
Authors: Adrian O’Dowd
Journal: BMJ (2008)

GPs are being asked by the BMA to comment on government health policy and on new private providers in general practice as part of an ongoing argument over extended hours.

This week the BMA launched a poll of its GP members on the two options put forward by the government to extend opening hours in general practice.

But it has also included several other political questions in the poll, which is thought likely to annoy the government and which indicates that relations are still frosty between the two sides.

Although the BMA is unhappy about either option, it has urged its members to choose the government’s first …
Radial Artery Grafts vs Saphenous Vein Grafts in Coronary Artery Bypass Surgery
Authors: Steven Goldman
Journal: JAMA (2011)

<h3>Context</h3>Arterial grafts are thought to be better conduits than saphenous vein grafts for coronary artery bypass grafting (CABG) based on experience with using the left internal mammary artery to bypass the left anterior descending coronary artery. The efficacy of the radial artery graft is less clear.<h3>Objective</h3>To compare 1-year angiographic patency of radial artery grafts vs saphenous vein grafts in patients undergoing elective CABG.<h3>Design, Setting, and Participants</h3>Multicenter, randomized controlled trial conducted from February 2003 to February 2009 at 11 Veterans Affairs medical centers among 757 participants (99% men) undergoing first-time elective CABG.<h3>Interventions</h3>The left internal mammary artery was used to preferentially graft the left anterior descending coronary artery whenever possible; the best remaining recipient vessel was randomized to radial artery vs saphenous vein graft.<h3>Main Outcome Measures</h3>The primary end point was angiographic graft patency at 1 year after CABG. Secondary end points included angiographic graft patency at 1 week after CABG, myocardial infarction, stroke, repeat revascularization, and death.<h3>Results</h3>Analysis included 733 patients (366 in the radial artery group, 367 in the saphenous vein group). There was no significant difference in study graft patency at 1 year after CABG (radial artery, 238/266; 89%; 95% confidence interval [CI], 86%-93%; saphenous vein, 239/269; 89%; 95% CI, 85%-93%; adjusted OR, 0.99; 95% CI, 0.56-1.74; P = .98). There were no significant differences in the secondary end points.<h3>Conclusion</h3>Among Veterans Affairs patients undergoing first-time elective CABG, the use of a radial artery graft compared with saphenous vein graft did not result in greater 1-year patency.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00054847
Efficacy of rituximab in systemic manifestations of primary Sjögren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry
Authors: Jacques-Eric Gottenberg, Gael Cinquetti, Claire Larroche, Bernard Combe, Eric Hachulla, Olivier Meyer, Edouard Pertuiset, Guy Kaplanski, Laurent Chiche, Jean-Marie Berthelot, Bruno Gombert, Philippe Goupille, Christian Marcelli, Séverine Feuillet, Jean Leone, Jean Sibilia, Charles Zarnitsky, Philippe Carli, Stephanie Rist, Philippe Gaudin, Carine Salliot, Muriel Piperno, Adeline Deplas, Maxime Breban, Thierry Lequerre, Pascal Richette, Charles Ghiringhelli, Mohamed Hamidou, Philippe Ravaud, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate the efficacy and safety of rituximab in patients with primary Sjögren's syndrome (pSS).The AutoImmune and Rituximab registry has included 86 patients with pSS treated with rituximab, prospectivey followed up every 6 months for 5 years.Seventy-eight patients with pSS (11 men, 67 women), who already had at least one follow-up visit, were analysed. Median age was 59.8 years (29-83), median duration of disease was 11.9 years (3-32). Indications for treatment were systemic involvement for 74 patients and only severe glandular involvement in four patients. The median European Sjögren's Syndrome disease activity index (ESSDAI) was 11 (2-31). 17 patients were concomitantly treated with another immunosuppressant agent. Median follow-up was 34.9 months (6-81.4) (226 patient-years). Overall efficacy according to the treating physician was observed in 47 patients (60%) after the first cycle of rituximab. Median ESSDAI decreased from 11 (2-31) to 7.5 (0-26) (p<0.0001). Median dosage of corticosteroid decreased from 17.6 mg/day (3-60) to 10.8 mg/day (p=0.1). Forty-one patients were retreated with rituximab. Four infusion reactions and one delayed serum sickness-like disease resulted in rituximab discontinuation. Three serious infections (1.3/100 patient-years) and two cancer-related deaths occurred.In common practice, the use of rituximab in pSS is mostly restricted to patients with systemic involvement. This prospective study shows good efficacy and tolerance of rituximab in patients with pSS and systemic involvement.
Terminal Dehydration as an Alternative to Physician-Assisted Suicide
Authors: Douglas P. Miller
Journal: Annals of Internal Medicine (1998)

Letters15 December 1998Terminal Dehydration as an Alternative to Physician-Assisted SuicideDouglas P. Miller, MDDouglas P. Miller, MDCatawba Memorial Hospital; Hickory, NC 28602Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-12-199812150-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The two articles that propose the voluntary forgoing of food and water as an attractive alternative method to physician-assisted suicide make me embarrassed to be a U.S. physician [1, 2].Willful starvation is not the same as refusing medical treatment, because eating and drinking (as opposed to artificial nutrition and hydration) are not medical treatments at all-let alone extraordinary or excessively burdensome treatments that patients are always morally free to refuse in good conscience.There is no moral distinction between self-inflicted death by refusing to eat or drink and death by a self-inflicted gunshot wound. The authors ...References1. Quill TE, Meier DE, Block SD, Billings JA. The debate over physician-assisted suicide: empirical data and convergent views. Ann Intern Med. 1998; 128:532-8. Google Scholar2. Miller FG, Meier DE. Voluntary death: a comparison of terminal dehydration and physician-assisted suicide. Ann Intern Med. 1998; 128:559-62. Google Scholar Author, Article, and Disclosure InformationAuthors: Douglas P. Miller, MDAffiliations: Catawba Memorial Hospital; Hickory, NC 28602 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1998Volume 129, Issue 12Page: 1081KeywordsBehaviorEatingFirearm injuriesFoodNutritionPatientsStarvationSuicide ePublished: 15 August 2000 Issue Published: 15 December 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Promoting Global Population Health While Constraining the Environmental Footprint
Authors: A.J. McMichael, C.D. Butler
Journal: Annual Review of Public Health (2011)

Populations today face increasing health risks from human-induced regional and global environmental changes and resultant ecological nonsustainability. Localized environmental degradation that has long accompanied population growth, industrialization, and rising consumerism has now acquired a global and often systemic dimension (e.g., climate change, disrupted nitrogen cycling, biodiversity loss). Thus, the economic intensification and technological advances that previously contributed to health gains have now expanded such that humanity's environmental (and ecological) footprint jeopardizes global population health. International data show, in general, a positive correlation of a population's health with level of affluence and size of per-person footprint. Yet, beyond a modest threshold, larger footprints afford negligible health gain and may impair health (e.g., via the rise of obesity). Furthermore, some lower-income countries have attained high levels of health. Many changes now needed to promote ecological (and social) sustainability will benefit local health. Continued improvement of global health could thus coexist with an equitably shared global environmental footprint.
Long-term survival in primary CNS lymphoma.
Authors: L E Abrey, L M DeAngelis, J Yahalom
Journal: Journal of Clinical Oncology (1998)

We have previously reported on 31 patients with primary CNS lymphoma (PCNSL) treated between 1986 and 1992 with methotrexate (MTX), cranial radiotherapy (RT), and high-dose cytarabine who remained free of disease longer than historical controls.We performed a follow-up analysis of our original cohort and now report their long-term survival and late treatment-related toxicity.The median cause-specific survival was 42 months, with a five-year survival of 22.3% compared with 3% to 4% in historical controls treated with RT alone. Age less than 50 years at diagnosis was a significant prognostic factor for survival (P = .01). Median disease-free survival was 40.3 months; 15 patients relapsed, all but one in the CNS. Late treatment-related toxicity was observed in nearly one third of patients and those more than 60 years of age were at substantially higher risk (P < .0001).Combined modality therapy for PCNSL has improved survival, but relapse is common and late neurologic toxicity is a significant complication. Although this approach is highly effective for younger patients, efficacious but less neurotoxic regimens need to be developed for older patients.
P-selectin glycoprotein ligand-1–deficient mice have impaired leukocyte tethering to E-selectin under flow
Authors: Lijun Xia, Markus Sperandio, Tadayuki Yago, J. Michael McDaniel, Richard D. Cummings, Sonia Pearson-White, Klaus Ley, Rodger P. McEver
Journal: Journal of Clinical Investigation (2002)

P-selectin glycoprotein ligand-1 (PSGL-1) mediates rolling of leukocytes on P-selectin under flow. The glycoproteins that enable leukocyte tethering to or rolling on E-selectin are not known. We used gene targeting to prepare PSGL-1–deficient (PSGL-1–/–) mice, which were healthy but had moderately elevated total blood leukocytes. Fluid-phase E-selectin bound to approximately 70% fewer sites on PSGL-1–/– than PSGL-1+/+ neutrophils. Compared with PSGL-1+/+ leukocytes, significantly fewer PSGL-1–/– leukocytes rolled on E-selectin in vitro, because their initial tethering to E-selectin was impaired. The residual cells that tethered rolled with the same shear resistance and velocities as PSGL-1+/+ leukocytes. Compared with PSGL-1+/+ mice, significantly fewer PSGL-1–/– leukocytes rolled on E-selectin in TNF-α–treated venules of cremaster muscle in which P-selectin function was blocked by an mAb. The residual PSGL-1–/– leukocytes that tethered rolled with slow velocities equivalent to those of PSGL-1+/+ leukocytes. These results reveal a novel function for PSGL-1 in tethering leukocytes to E-selectin under flow.
Androgen Receptors in the Brain: What Are We Measuring?*
Authors: PETER J. SHERIDAN
Journal: Endocrine Reviews (1983)

STUDIES dealing with androgen receptors in the brain have made use of two now well accepted techniques, namely autoradiography (in vivo) and receptor binding (in vitro), to define and characterize the receptors. It was generally assumed that the two approaches were providing corroborative yet different information about the same system. Recent autoradiographic data indicate that this is probably not the case and that in fact, they are probably characterizing different systems in the brain. Androgens have long been known to modify the expression of both sexual behavior (1, 2) and aggressive (3) behavior presumably by acting on the brain. This was later confirmed by studies in which testosterone was implanted directly into the brain (4). Implants of androgens into the median eminence, but not the pituitary gland, have also been shown to result in testicular regression and accessory sex gland atrophy (5, 6) and later to modulate gonadotropin secretion itself (7–9).
Illness and injury in athletes during the competition period at the London 2012 Paralympic Games: development and implementation of a web-based surveillance system (WEB-IISS) for team medical staff
Authors: Wayne Derman, Martin Schwellnus, Esme Jordaan, Cheri A Blauwet, Carolyn Emery, Pia Pit-Grosheide, Norma-Angelica Patino Marques, Oriol Martinez-Ferrer, Jaap Stomphorst, Peter Van de Vliet, Nick Webborn, Stuart E Willick
Journal: British Journal of Sports Medicine (2013)

In this study we describe (1) the implementation of a novel web-based injury and illness surveillance system (WEB-IISS) for use by a team of physicians at multisport events and (2) the incidence and characteristics of injuries and illness in athletes during the London 2012 Paralympic Games.Overall, 3565 athletes from 160 of the 164 participating countries were followed daily over a 14-day period, consisting of a precompetition period (3 days), and a competition period (11 days) (49 910 athlete-days). Daily injury and illness data were obtained from teams with their own medical support (78 teams, 3329 athletes) via the WEB-IISS, and without their own medical support through the London Organising Committee of the Olympic Games and Paralympic Games database (82 teams and 236 athletes).There were no differences between incidence rates (IR) of injury and illness, or between the precompetition and competition periods. The IR of injury during the competition period was 12.1/1000 athlete-days, with an incidence proportion (IP) of 11.6% (95% CI 11.0% to 13.3%). Upper limb injuries (35%), particularly of the shoulder (17%) were most common. The IR of illness during the competition period was 12.8/1000 athlete-days (95% CI 12.18 to 1421), with an IP of 10.2%. The IP was highest in the respiratory system (27.4%), skin (18.3%) and the gastrointestinal (14.5%) systems.During the competition period, the IR and IP of illness and injury at the Games were similar and comparable to the observed rates in other elite competitions. In Paralympic athletes, the IP of upper limb injuries is higher than that of lower limb injuries and non-respiratory illnesses are more common.
Three Classes of Genes Mutated In Colorectal Cancers with Chromosomal Instability
Authors: Zhenghe Wang, Jordan M. Cummins, Dong Shen, Daniel P. Cahill, Prasad V. Jallepalli, Tian-Li Wang, D. Williams Parsons, Giovanni Traverso, Mark Awad, Natalie Silliman, Janine Ptak, Steve Szabo, James K. V. Willson, Sanford D. Markowitz, Michael L. Goldberg, Roger Karess, Kenneth W. Kinzler, Bert Vogelstein, Victor E. Velculescu, Christoph Lengauer
Journal: Cancer Research (2004)

Abstract Although most colorectal cancers are chromosomally unstable, the basis for this instability has not been defined. To determine whether genes shown to cause chromosomal instability in model systems were mutated in colorectal cancers, we identified their human homologues and determined their sequence in a panel of colorectal cancers. We found 19 somatic mutations in five genes representing three distinct instability pathways. Seven mutations were found in MRE11, whose product is involved in double-strand break repair. Four mutations were found among hZw10, hZwilch/FLJ10036, and hRod/KNTC, whose products bind to one another in a complex that localizes to kinetochores and controls chromosome segregation. Eight mutations were found in Ding, a previously uncharacterized gene with sequence similarity to the Saccharomyces cerevisiae Pds1, whose product is essential for proper chromosome disjunction. This analysis buttresses the evidence that chromosomal instability has a genetic basis and provides clues to the mechanistic basis of instability in cancers.
Dermoscopy of skin lesions in two patients with xeroderma pigmentosum
Authors: J. Malvehy, S. Puig, R.M. Marti-Laborda
Journal: British Journal of Dermatology (2005)

Background Xeroderma pigmentosum (XP) is a rare disorder produced by a genetic defect in the repair of DNA damage caused by ultraviolet radiation. The early diagnosis of malignant skin tumours is crucial in the survival of patients with XP, but this is not easy even for experienced dermatologists due to the presence of a high number of actinic lesions. Dermoscopy is a new diagnostic method that increases the diagnostic accuracy for skin tumours. Objectives To describe the clinical and dermoscopic features of different benign and malignant lesions [focusing on malignant melanoma, basal cell carcinoma (BCC) and benign melanocytic naevi] in two patients with XP. Methods Three dermatologists with experience in pigmented skin lesions and dermoscopy examined two siblings with XP over a period of 54 months. Diagnosis of skin tumours was obtained using clinical examination and dermoscopy with 10-fold magnification and digital images. All the tumours with criteria of malignancy were excised for further histopathological analyses. Results Multiple skin tumours showing some degree of pigmentation were detected in the patients. Clinical and dermoscopic examination allowed the discrimination of four melanomas (three of them in situ), 26 BCCs and five dysplastic naevi from other pigmented skin lesions. The features and parameters previously described for dermoscopy were shown to be appropriate for the recognition of tumours in our patients with XP. Generalized actinic lentigos were distinguished from BCCs by the presence of a delicate brown pigmented network. Fine vessels from poikiloderma were differentiated from the arborizing telangiectasia of BCC. Conclusions The dermoscopic findings in the tumours were similar to those previously described in patients not affected by XP. Diagnosis by dermoscopic pattern analyses allowed a correct classification of malignant tumours in these cases.