tbuckley/cabot-search huggingface dataset:
High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids
Authors: M. McMahon, B. J. Skaggs, L. Sahakian, J. Grossman, J. FitzGerald, N. Ragavendra, C. Charles-Schoeman, M. Chernishof, A. Gorn, J. L. Witztum, W. K. Wong, M. Weisman, D. J. Wallace, A. La Cava, B. H. Hahn
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Patients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population. <h3>Objective</h3> To examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis. <h3>Methods</h3> Carotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed. <h3>Results</h3> Leptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p&lt;0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p&lt;0.001), age (OR=1.1, p&lt;0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p&lt;0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present. <h3>Conclusions</h3> High leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis.
Early diagnosis of pancreatic cancer; looking for a needle in a haystack?
Authors: Marco J Bruno
Journal: Gut (2012)

The paper by Kanda et al highlights a potentially novel method for the early diagnosis of pancreatic neoplasia.1 Although our understanding of the pathological and molecular events of pancreatic cancer has advanced significantly over the past years, we are still far away from a clinically meaningful breakthrough in its treatment as demonstrated by the poor survival statistics which have hardly changed over the past decades.2 ,3 In light of this sobering observation, it is important to consider other ways of trying to lower the mortality of this dreadful disease. Primary prevention through life style changes of established risk factors like smoking has a considerable potential to reduce the number of pancreatic cancer deaths,4 but it is well known that such behavioural changes are difficult to accomplish. Secondary prevention by screening the general population for pancreatic cancer is not feasible at present because of its low incidence and the lack of a non-invasive, reliable and cheap screening tool. However, it is estimated that about 10% of all pancreatic cancer cases are caused by inherited (genetic) factors with some individuals carrying a life time risk up to 55%.5 Affected individuals are known mutation carriers of pancreatic cancer prone hereditary (tumour) syndromes (eg, familial atypical multiple mole melanoma syndrome, Peutz–Jeghers syndrome, breast cancer 1 and …
Tolmetin-Induced Aseptic Meningitis
Authors: Gary B. Ruppert
Journal: JAMA (1981)

A 21-year-old woman with systemic lupus erythematosus (SLE) had meningismus, conjunctivitis, lymphadenopathy, and elevation of liver function values following ibuprofen therapy. All symptoms and laboratory value abnormalities resolved rapidly when the drug therapy was stopped. Two years later, a similar reaction occurred after taking tolmetin sodium. Fever, adenopathy, aseptic meningitis with a polymorphonuclear pleocytosis, and serum transaminase level elevations resolved rapidly after use of the drug was discontinued. The mechanism of this reaction to nonsteroidal antiinflammatory drugs in patients with SLE is not known.
Specialist breast and ovarian cancer clinics should be staffed by oncologist nurses
Authors: B. A Stoll
Journal: BMJ (1996)

EDITOR,—Harry Campbell and colleagues set out the need for specialist NHS clinics to provide advice to the many women who fear that they are at high risk of breast and ovarian cancer.1 I agree that such a need exists, but I disagree with the authors' suggested staffing model. Campbell and colleagues suggest that …
Cerebral cortex oxygen delivery and exercise limitation in patients with COPD
Authors: Ioannis Vogiatzis, Zafeiris Louvaris, Helmut Habazettl, Vasileios Andrianopoulos, Harrieth Wagner, Charis Roussos, Peter D. Wagner, Spyros Zakynthinos
Journal: European Respiratory Journal (2012)

In healthy humans, cerebral oxygen desaturation during exercise affects motor unit recruitment, while oxygen supplementation enhances cerebral oxygenation and work capacity. It remains unknown whether in patients with chronic obstructive pulmonary disease (COPD), the well-documented improvement in exercise tolerance with oxygen supplementation may also be partly due to the increase in cerebral oxygenation. Using near infrared spectroscopy, we measured both frontal cerebral cortex blood flow (CBF) using indocyanine green dye and cerebrovascular oxygen saturation ( S t,O 2 ) in 12 COPD patients during constant-load exercise to exhaustion at 75% of peak capacity. Subjects exercised while breathing air, 100% oxygen or normoxic heliox, the latter two in balanced order. Time to exhaustion while breathing air was less than for either oxygen or heliox (mean± sem 394±35 versus 670±43 and 637±46 s, respectively). Under each condition, CBF increased from rest to exhaustion. At exhaustion, CBF was higher while breathing air and heliox than oxygen (30.9±2.3 and 31.3±3.5 versus 26.6±3.2 mL·min −1 per 100 g, respectively), compensating for the lower arterial oxygen content (C a,O 2 ) in air and heliox, and leading to similar cerebral cortex oxygen delivery (CQ O 2 for air was 5.3±0.4, for oxygen was 5.5±0.6 and for heliox was 5.6±1.0 mL O 2 per min per 100 g). In contrast, end-exercise S t,O 2 was greater while breathing oxygen compared with air or heliox (67±4 versus 57±3 and 53±3%, respectively), reflecting C a,O 2 rather than CQ O 2 . Prolonged time to exhaustion by breathing oxygen and heliox, despite these having a similar CQ O 2 to air, a lower S t,O 2 with heliox than oxygen, and yet similar endurance time and similar S t,O 2 in air and heliox despite greater endurance with heliox, do not support the hypothesis that an improvement in cerebral cortex oxygen availability plays a contributing role in increasing exercise capacity with oxygen or heliox in patients with COPD.
Association of American Medical Colleges and American Medical Association Joint Statement on Physician Workforce Planning and Graduate Medical Education Reform Policies
Authors: Jordan J. Cohen
Journal: JAMA (1994)

THE Association of American Medical Colleges (AAMC) and the American Medical Association (AMA) recognize that there are a number of policy issues related to the size and specialty mix of the physician workforce and the organization and funding of graduate medical education (GME) and the academic environment that must be addressed on an ongoing basis to further the health of the public and respond to the goals and requirements of health system reform. Both associations concur with the need for a better balance between generalist physicians and nongeneralist specialty physicians and are concerned that the size of the future physician workforce may exceed both the public's need and the demand for physicians' services. Both associations also concur that planned changes in the size or specialty mix of the workforce must be approached thoughtfully and deliberately. The AMA and AAMC offer the following principles to guide these deliberations. A national physician
Nuclear Localization of Apoptosis Protease Activating Factor-1 Predicts Survival after Tumor Resection in Early-Stage Non–Small Cell Lung Cancer
Authors: Benjamin Besse, Céline Candé, Jean-Philippe Spano, Antoine Martin, David Khayat, Thierry Le Chevalier, Thomas Tursz, Laure Sabatier, Jean-Charles Soria, Guido Kroemer
Journal: Clinical Cancer Research (2004)

Abstract The proapoptotic protein apoptosis protein activating factor-1 (Apaf-1), which is normally located in the cytoplasm, can translocate to the nucleus before non-small cell lung carcinoma (NSCLC) cells manifest signs of apoptosis such as mitochondrial damage, caspase activation, or chromatin condensation. This may indicate a stage of imminent apoptosis. Importantly, we found that 24% (15 of 62) of resected stage I NSCLC (T1N0M0 or T2N0M0), manifested a marked nuclear localization of Apaf-1 (Apaf-1Nuc), as compared with the mostly cytoplasmic localization of Apaf-1 found in the remaining tumors (Apaf-1Cyt). After a median follow-up of 6.31 years, the actuarial 5-year overall survival rates were 89% (56–98%) in the Apaf-1Nuc group and 54% (36–71%) in the Apaf-1Cyt group (P = 0.039). No correlation between the subcellular localization of Apaf-1 and that of p53 and Hsp70 could be established. Thus, the subcellular location of Apaf-1 (but not that of p53 or Hsp70) constitutes an accurate prognostic factor for overall survival in NSCLC.
Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis
Authors: T Mimura
Journal: Gut (2003)

<h3>Objective</h3> To examine the association of 24-hour time-use compositions with mental health in a large, geographically diverse sample of UK adolescents. <h3>Design</h3> Cross-sectional, secondary data analysis. <h3>Setting</h3> Millennium Cohort Study (sixth survey), a UK-based prospective birth cohort. <h3>Participants</h3> Data were available from 4642 adolescents aged 14 years. Analytical samples for weekday and weekend analyses were n=3485 and n=3468, respectively (45% boys, 85% white ethnicity). <h3>Primary and secondary outcome measures</h3> Primary outcome measures were the Strengths and Difficulties Questionnaire (SDQ, socioemotional behaviour), Mood and Feelings Questionnaire (MFQ, depressive symptoms) and Rosenberg Self-Esteem Scale (RSE, self-esteem). Behavioural exposure data were derived from 24-hour time-use diaries. <h3>Results</h3> On weekdays, participants spent approximately 54% of their time in sleep, 3% in physical activity, 9% in school-related activities, 6% in hobbies, 11% using electronic media and 16% in domestic activities. Predicted differences in SDQ, MFQ and RSE were statistically significant for all models (weekday and weekend) that simulated the addition or removal of 15 min physical activity, with an increase in activity being associated with improved mental health and vice versa. Predicted differences in RSE were also significant for simulated changes in electronic media use; an increase in electronic media use was associated with reduced self-esteem. <h3>Conclusion</h3> Small but consistent associations were observed between physical activity, electronic media use and selected markers of mental health. Findings support the delivery of physical activity interventions to promote mental health during adolescence, without the need to specifically target or protect time spent in other activities.
Conflicts of interest that are bigger than money but never disclosed
Authors: A. Natarajan
Journal: Journal of the Royal Society of Medicine (2006)

The editorial 'Too little quality; too many doctors' (June 2006 JRSM 1 ) is incorrect to suggest that the General Medical Council (GMC) had a 'sudden demand for overseas graduates to have a work permit'.The GMC does not have any visa requirements for international medical graduates (IMGs).The Home Office is responsible for setting visa requirements.International medical graduates are responsible for ensuring that they have the appropriate visa when they enter the UK.
Leaving the professional tennis circuit: exploratory study of experiences and reactions from elite female athletes
Authors: J A Young, A J Pearce, R Kane, M Pain
Journal: British Journal of Sports Medicine (2006)

In 2002, Tennis Australia commissioned a report into the experiences of elite female past players on leaving the professional tennis circuit. Australian players who were in the top 800 of the Women’s Tennis Association (WTA) end of year rankings and who had left the professional circuit within the previous 15 years were asked by mail to respond to a questionnaire. The questionnaire asked players to describe their feelings about leaving the tour during the time leading up to leaving the tour to two years after retirement. The main findings of the study suggested that those who planned to leave the tour found the transition process easy, whereas those who did not plan to leave the tour found the process difficult. Most players (66%) did not regret leaving the tour, and, although the remaining players responded that they regretted leaving, none attempted a comeback. Tennis Australia has implemented strategies to assist current players on the professional tour based on the results of this study.
Rapid recovery from acute transverse myelitis in an elite female swimmer * Commentary * Commentary
Authors: G Dubnov, N W Constantini
Journal: British Journal of Sports Medicine (2006)

Rubella is now an uncommon disease, and its neurological complications are rarely encountered. One complication, acute transverse myelitis, has been described in a few case reports and usually has an unfavourable outcome. The case is presented of an elite swimmer who developed transverse myelitis after rubella, which was treated with methylprednisolone. The recovery was so rapid and complete that two months after the acute event she broke a national swimming record.
Cyclooxygenase-2 Transcription Is Regulated by Human Papillomavirus 16 E6 and E7 Oncoproteins: Evidence of a Corepressor/Coactivator Exchange
Authors: Kotha Subbaramaiah, Andrew J. Dannenberg
Journal: Cancer Research (2007)

Abstract Cyclooxygenase (COX-2) is overexpressed in human papillomavirus (HPV)-induced diseases, including cervical cancer. Although HPV E6 and E7 oncoproteins have been causally linked to cervical carcinogenesis, their effects on COX-2 gene expression are unknown. Increased levels of COX-2 mRNA, protein, and prostaglandin E2 synthesis were detected in HPV16 E6- and E7-expressing cervical cancer cells (CaSki and SiHa) compared with an uninfected cervical cancer cell line (C33A). HPV16 E6 and E7 oncoproteins induced COX-2 transcription by activating the epidermal growth factor receptor (EGFR)→Ras→mitogen-activated protein kinase pathway. Interestingly, HPV16 oncoproteins stimulated EGFR signaling, in part, by inducing the release of amphiregulin, an EGFR ligand. The inductive effects of HPV16 E6 and E7 were mediated by enhanced binding of activator protein-1 to the cyclic AMP (cAMP)-responsive element (−59/−53) of the COX-2 promoter. The potential contribution of coactivators and corepressors to HPV16 E6- and E7-mediated induction of COX-2 was also investigated. Chromatin immunoprecipitation assays indicated that E6 and E7 oncoproteins induced the recruitment of phosphorylated c-Jun, c-Fos, UbcH5, and cAMP-responsive element binding protein–binding protein/p300 to the COX-2 promoter. In contrast, E6 and E7 inhibited the binding of the histone deacetylase 3-nuclear receptor corepressor (NCoR) complex to the COX-2 promoter. Moreover, overexpression of NCoR blocked E6- and E7-mediated stimulation of the COX-2 promoter. Taken together, these results indicate that HPV16 E6 and E7 oncoproteins stimulated COX-2 transcription by inducing a corepressor/coactivator exchange. To our knowledge, this study also provides the first evidence that NCoR can function as a repressor of COX-2 gene expression. [Cancer Res 2007;67(8):3976–85]
Kielin/Chordin-Like Protein Attenuates both Acute and Chronic Renal Injury
Authors: Abdul Soofi, Peng Zhang, Gregory R. Dressler
Journal: Journal of the American Society of Nephrology (2013)

The secreted kielin/chordin-like (KCP) protein, one of a family of cysteine-rich proteins, suppresses TGF-β signaling by sequestering the ligand from its receptor, but it enhances bone morphogenetic protein (BMP) signaling by promoting ligand-receptor interactions. Given the critical roles for TGF-β and BMP proteins in enhancing or suppressing renal interstitial fibrosis, respectively, we examined whether secreted KCP could attenuate renal fibrosis in mouse models of chronic and acute disease. Transgenic mice that express KCP in adult kidneys showed significantly less expression of collagen IV, α-smooth muscle actin, and other markers of disease progression in the unilateral ureteral obstruction model of renal interstitial fibrosis. In the folic acid nephrotoxicity model of acute tubular necrosis, mice expressing KCP survived high doses of folic acid that were lethal for wild-type mice. With a lower dose of folic acid, mice expressing KCP exhibited improved renal recovery compared with wild-type mice. Thus, these data suggest that extracellular regulation of the TGF-β/BMP signaling axis by KCP, and by extension possibly other cysteine-rich domain proteins, can attenuate both acute and chronic renal injury.
Accessory cell function of human B cells. I. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line.
Authors: G Scala, Y D Kuang, R E Hall, A V Muchmore, J J Oppenheim
Journal: The Journal of Experimental Medicine (1984)

In the present paper we report that the ROHA -9 cell line, an Epstein-Barr virus (EBV)-transformed human B cell line with accessory cell capabilities, constitutively secretes a soluble factor with the biochemical and biological characteristics of human monocyte-derived IL-1. The IL-1 derived from ROHA -9 augmented murine thymocyte proliferation and enhanced the proliferative response of human T lymphocytes to concanavalin A (Con A). The ROHA -9-derived IL-1 activity eluted from Sephacryl S-200 in two peaks, at 15- 18K and 32- 35K mol wt, eluted from DEAE-Sephacel at 50-80 and 110-130 mM NaCl, and showed charge heterogeneity with peaks at pI 7.3, 6.1, and 4.1 on isoelectrofocusing (IEF). These findings suggest that B cells may elaborate an IL-1-like activity. During the logarithmic growth of ROHA -9 cells, a inhibitory factor that inhibited the response of mouse thymocytes to IL-1 was also produced. This factor had a mol wt of 95K on Sephacryl S-200, eluted at 150 mM NaCl on DEAE-Sephacel and showed a peak of pI 4.7 on preparative IEF. The inhibitory factor appeared to be selective in its effects on IL-1 responses, since it did not inhibit the activity of IL-2 on mouse thymocytes or on the growth of the IL-2-dependent CT6 cell line. This "contra-IL-1" inhibited the response of murine thymocytes to suboptimal (1 microgram/ml) but not optimal (10 micrograms/ml) doses of Con A and the response of human peripheral blood lymphocytes to streptolysin O ( SLO ) or to alloantigens. Moreover, the factor could be absorbed by mouse thymocytes but not by CT6 cells, and such thymocytes pretreated with contra-IL-1 failed to response to IL-1. Although this inhibitor is the product of a transformed B cell line, it may be representative of regulatory substances that normally control IL-1 activities either at the extracellular or intracellular level.
Randomized Multicenter Trial of Hyperthermic Isolated Limb Perfusion With Melphalan Alone Compared With Melphalan Plus Tumor Necrosis Factor: American College of Surgeons Oncology Group Trial Z0020
Authors: Wendy R. Cornett, Linda M. McCall, Rebecca P. Petersen, Merrick I. Ross, Henry A. Briele, R. Dirk Noyes, Jeffrey J. Sussman, William G. Kraybill, John M. Kane, H. Richard Alexander, Jeffrey E. Lee, Paul F. Mansfield, James F. Pingpank, David J. Winchester, Richard L. White, Vijaya Chadaram, James E. Herndon, Douglas L. Fraker, Douglas S. Tyler
Journal: Journal of Clinical Oncology (2006)

To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma.Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status.The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively).In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.