tbuckley/cabot-search huggingface dataset:
Epigenetic modifications as key regulators of Waldenstrom's Macroglobulinemia biology
Authors: Antonio Sacco, Ghayas C Issa, Yong Zhang, Yang Liu, Patricia Maiso, Irene M Ghobrial, Aldo M Roccaro
Journal: Journal of Hematology & Oncology (2010)

Abstract Waldenstrom's Macroglobulinemia is a low-grade B-cell lymphoma characterized by the presence of lymphoplasmacytic cells in the bone marrow and a monoclonal immunoglobulin M in the circulation. Recent evidences support the hypothesis that epigenetic modifications lead to Waldesntrom cell proliferation and therefore play a crucial role in the pathogenesis of this disease. Indeed, while cytogenetic and gene expression analysis have demonstrated minimal changes; microRNA aberrations and modification in the histone acetylation status of primary Waldenstrom Macroglobulinemia tumor cells have been described. These findings provide a better understanding of the underlying molecular changes that lead to the initiation and progression of this disease.
Shp1 regulates T cell homeostasis by limiting IL-4 signals
Authors: Dylan J. Johnson, Lily I. Pao, Salim Dhanji, Kiichi Murakami, Pamela S. Ohashi, Benjamin G. Neel
Journal: The Journal of Experimental Medicine (2013)

The protein-tyrosine phosphatase Shp1 is expressed ubiquitously in hematopoietic cells and is generally viewed as a negative regulatory molecule. Mutations in Ptpn6, which encodes Shp1, result in widespread inflammation and premature death, known as the motheaten (me) phenotype. Previous studies identified Shp1 as a negative regulator of TCR signaling, but the severe systemic inflammation in me mice may have confounded our understanding of Shp1 function in T cell biology. To define the T cell–intrinsic role of Shp1, we characterized mice with a T cell–specific Shp1 deletion (Shp1fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1(fl/fl) CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4⁺ T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. After IL-4 stimulation of Shp1- deficient T cells, Stat 6 activation was sustained, leading to enhanced Th2 skewing. Accordingly, we observed elevated serum IgE in the steady state. Blocking or genetic deletion of IL-4 in the absence of Shp1 resulted in a marked reduction of the CD44hi population. Therefore, Shp1 is an essential negative regulator of IL-4 signaling in T lymphocytes.
Inactivation of hMLH1 and hMSH2 by promoter methylation in primary non-small cell lung tumors and matched sputum samples
Authors: Yi-Ching Wang, Yung-Pin Lu, Ruo-Chia Tseng, Ruo-Kai Lin, Jer-Wei Chang, Jung-Ta Chen, Chuen-Ming Shih, Chih-Yi Chen
Journal: Journal of Clinical Investigation (2003)

We performed a genetic and epigenetic study of the hMLH1 and hMSH2 mismatch repair genes in resected primary tumors from 77 non-small cell lung cancer (NSCLC) patients. The molecular alterations examined included the loss of mRNA and protein expression as well as promoter methylation, and the allelic imbalance of the chromosomal regions that harbor the genes. We found that 78% and 26% of patients showed at least one type of molecular alteration within the hMLH1 and hMSH2 genes, respectively. Promoter methylation of the hMLH1 gene was present in 55.8% of tumors, and was significantly associated with the reduction in mRNA and protein expression (P = 0.001). A 72% concordance of aberrant methylation in sputum samples with matched resected tumors was found. In addition, a 93% consistency between the promoter methylation and the mRNA expression of the hMSH2 gene was found in 14 female NSCLC patients. However, no correlation was found between the expression of hMLH1 and hMSH2 proteins and the allelic imbalance of five microsatellite markers closely linked to the genes. Our results suggest that hMLH1 is the major altered mismatch repair gene involved in NSCLC tumorigenesis, and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMLH1 gene may be identified in sputum samples to serve as a potential diagnostic marker of NSCLC.
Manipulating the Epigenome in Germinal Center Lymphomas: Is It Getting Easier and <i>EZier</i>?
Authors: Jennifer E. Amengual, Owen A. O'Connor
Journal: Clinical Cancer Research (2014)

Mutations affecting key epigenetic modifiers tend to cluster in malignancies in which cells of origin lie in the germinal center (GC). EZH2, as transcriptional repressor, is mutated in high frequency in Chinese and Western patients with follicular lymphoma and may represent a rational target for GC-derived lymphomas. .
Treatment of Fluorouracil-Refractory Patients With Liver Metastases From Colorectal Cancer by Using Yttrium-90 Resin Microspheres Plus Concomitant Systemic Irinotecan Chemotherapy
Authors: Guy A. van Hazel, Nick Pavlakis, David Goldstein, Ian N. Olver, Michael J. Tapner, David Price, Geoffrey D. Bower, Gregory M. Briggs, Monica A. Rossleigh, D. James Taylor, Jacob George
Journal: Journal of Clinical Oncology (2009)

Purpose Liver metastases are the principal cause of death in patients with advanced colorectal cancer (CRC). Irinotecan is a chemotherapeutic agent used in the treatment of CRC and has demonstrated synergistic potential when used with radiation. Radioembolization with yttrium-90 microspheres has demonstrated increased response and survival rates when given with fluorouracil chemotherapy. This study's goal was to evaluate the maximum-tolerated dose of concomitant irinotecan and radioembolization in fluorouracil-refractory patients with CRC hepatic metastases. Patients and Methods Twenty-five irinotecan-naïve patients who had experienced relapse after previous chemotherapy were enrolled onto three dose-escalating groups. Irinotecan was administered at 50, 75, or 100 mg/m 2 on days 1 and 8 of a 3-week cycle for the first two cycles, and full irinotecan doses (ie, 100 mg/m 2 ) were administered during cycles 3 to 9. Radioembolization was administered during the first chemotherapy cycle. Results Most patients experienced acute, self-limiting abdominal pain and nausea. Mild lethargy and anorexia were common. Grades 3 to 4 events were seen in three of six patients at 50 mg/m 2 (obstructive jaundice, thrombocytopenia, diarrhea), in five of 13 patients at 75 mg/m 2 (neutropenia, leukopenia, thrombocytopenia, elevated alkaline phosphatase, abdominal pain, ascites, fatigue) and in four of six patients at 100 mg/m 2 (diarrhea, deep vein thrombosis, constipation, leukopenia). Eleven (48%) of 23 patients had a partial response, and nine patients (39%) had stable disease. The median progression-free survival was 6.0 months; the median survival was 12.2 months. Conclusion Concomitant use of radioembolization plus irinotecan did not reach a maximum-tolerated dose. The recommended dose of irinotecan in this setting is 100 mg/m 2 on days 1 and 8 of a 3-week cycle.
Statins May Protect Against Hepatocellular Carcinoma Development in Patients Infected With Hepatitis C Virus, but What Are the Mechanisms?
Authors: Sophie Clément, Marion Peyrou, Michelangelo Foti, Francesco Negro
Journal: Journal of Clinical Oncology (2013)

The population-based cohort study by Tsan et al 1 showed that statin use was associated with a significantly reduced risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus infection (adjusted hazard ratio, 0.53; 95% CI, 0.49 to 0.58).However, we would like to raise a significant issue.As the authors acknowledge, not all possible confounding factors were adjusted for, including body mass index, smoking, alcohol use, and other indicators of health and socioeconomic status.On the other hand, a socioeconomic gradient in the use of and adherence to statin treatments has been well documented in the literature. [2]3][4][5][6] In particular, individuals of higher socioeconomic classes are more likely to be given a statin.A social gradient in statin use may reflect social inequalities in health care use or health care quality, as well as systematic differences in factors such as tobacco use, nutrition, physical activity, and obesity.Thus, socioeconomic inequalities in statin use may have confounded the observed association between statin use and the risk of HCC in patients with hepatitis C virus infection, especially given that meta-analyses of randomized clinical trials have constantly shown that statins do not affect cancer risk. 7,8Nevertheless, we agree that statins merit further study in high-risk populations to elucidate their potential role in HCC chemoprevention.
Frontiers in climate change–disease research
Authors: Jason R. Rohr, Andrew P. Dobson, Pieter T.J. Johnson, A. Marm Kilpatrick, Sara H. Paull, Thomas R. Raffel, Diego Ruiz-Moreno, Matthew B. Thomas
Journal: Trends in Ecology & Evolution (2011)

The notion that climate change will generally increase human and wildlife diseases has garnered considerable public attention, but remains controversial and seems inconsistent with the expectation that climate change will also cause parasite extinctions. In this review, we highlight the frontiers in climate change-infectious disease research by reviewing knowledge gaps that make this controversy difficult to resolve. We suggest that forecasts of climate-change impacts on disease can be improved by more interdisciplinary collaborations, better linking of data and models, addressing confounding variables and context dependencies, and applying metabolic theory to host-parasite systems with consideration of community-level interactions and functional traits. Finally, although we emphasize host-parasite interactions, we also highlight the applicability of these points to climate-change effects on species interactions in general.
Cytodestructive Mechanisms Provoked by Food Antigens
Authors: W. K. PODLESKI
Journal: Allergy (1985)

Antibody‐dependent, allergic autocytotoxicity (ACT) is an in vitro process through which WBC from patients and/or controls, passively sensitized with RAST positive serum, are damaged in the presence of corresponding food antigens. Studies among 13 patients, sensitive to cow milk, corn and wheat, and 13 asymptomatic controls revealed that antibody‐dependent ACT is mediated by thermolabile cytotoxic factor, presumably IgE antibody. The resultant cellular interactions might contribute to the induction of the autoimmune response.
Influence of lung volume reduction surgery (LVRS) on health related quality of life in patients with chronic obstructive pulmonary disease
Authors: R S Goldstein
Journal: Thorax (2003)

<b>Background:</b> The clinical value of LVRS has been questioned in the absence of trials comparing it with pulmonary rehabilitation, the prevailing standard of care in COPD. Patients with heterogeneous emphysema are more likely to benefit from volume reduction than those with homogeneous disease. Disease specific quality of life is a responsive interpretable outcome that enables health professionals to identify the magnitude of the effect of an intervention across several domains. <b>Methods:</b> Non-smoking patients aged &lt;75 years with severe COPD (FEV<sub>1</sub> &lt;40% predicted, FEV<sub>1</sub>/FVC &lt;0.7), hyperinflation, and evidence of heterogeneity were randomised to surgical or control groups after pulmonary rehabilitation and monitored at 3 month intervals for 12 months with no crossover between the groups. The primary outcome was disease specific quality of life as measured by the Chronic Respiratory Questionnaire (CRQ). Treatment failure was defined as death or functional decline (fall of 1 unit in any two domains of the CRQ). Secondary outcomes included pulmonary function and exercise capacity. <b>Results:</b> LVRS resulted in significant between group differences in each domain of the CRQ at 12 months (change of 0.5 represents a small but important difference): dyspnoea 1.9 (95% confidence interval (CI) 1.3 to 2.6; p&lt;0.0001); emotional function 1.5 (95% CI 0.9 to 2.1; p&lt;0.0001); fatigue 2.0 (95% CI 1.4 to 2.6; p&lt;0.0001); mastery 1.8 (95% CI 1.2 to 2.5; p&lt;0.0001). In the control group one of 27 patients died and 16 experienced functional decline over 12 months. In the surgical group four of 28 patients died and three experienced functional decline (hazard ratio = 3.1 (95% CI 1.3 to 7.6; p=0.01). Between group improvements (p&lt;0.05) in lung volumes, flow rates, and exercise were sustained at 12 months (RV −47% predicted (95% CI −71 to −23; p=0.0002); FEV<sub>1</sub> 0.3 l (95% CI 0.1 to 0. 5; p=0.0003); submaximal exercise 7.3 min (95% CI 3.9 to 10.8; p&lt;0.0001); 6 minute walk 66 metres (95% CI 32 to 101; p=0.0002). <b>Conclusions:</b> In COPD patients with heterogeneous emphysema, LVRS resulted in important benefits in disease specific quality of life compared with medical management, which were sustained at 12 months after treatment.
Childhood Body-Mass Index and the Risk of Coronary Heart Disease in Adulthood
Authors: Jennifer L. Baker, Lina W. Olsen, Thorkild I.A. Sørensen
Journal: New England Journal of Medicine (2007)

The worldwide epidemic of childhood obesity is progressing at an alarming rate. Risk factors for coronary heart disease (CHD) are already identifiable in overweight children. The severity of the long-term effects of excess childhood weight on CHD, however, remains unknown.We investigated the association between body-mass index (BMI) in childhood (7 through 13 years of age) and CHD in adulthood (25 years of age or older), with and without adjustment for birth weight. The subjects were a cohort of 276,835 Danish schoolchildren for whom measurements of height and weight were available. CHD events were ascertained by linkage to national registers. Cox regression analyses were performed.In 5,063,622 person-years of follow-up, 10,235 men and 4318 women for whom childhood BMI data were available received a diagnosis of CHD or died of CHD as adults. The risk of any CHD event, a nonfatal event, and a fatal event among adults was positively associated with BMI at 7 to 13 years of age for boys and 10 to 13 years of age for girls. The associations were linear for each age, and the risk increased across the entire BMI distribution. Furthermore, the risk increased as the age of the child increased. Adjustment for birth weight strengthened the results.Higher BMI during childhood is associated with an increased risk of CHD in adulthood. The associations are stronger in boys than in girls and increase with the age of the child in both sexes. Our findings suggest that as children are becoming heavier worldwide, greater numbers of them are at risk of having CHD in adulthood.
MOTOR CARS FOR MEDICAL MEN: LIGHT CAR DEVELOPMENTS
Authors: H. M. Buist
Journal: BMJ (1915)

that there is little to add to the commluendation tL-'.bestowed oln the bool.It makes no claimi to originalU y, but, as the authors, state, is founded on tlle stanidardl works on tlle subject, keeping in view its special object, to adapt tlhe principles of these works to the conditions wlhiclh prevail in India.Tlle nlew edition lhas been carefully revised, alnd in some places extended, to bring it uip to date, and witlh the salmle view the number of illustrations lhas been somewhlat increased.We may say that the book fulfils its object satisfactorily.
Re: A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma
Authors: E. Winquist, S. Berry
Journal: JNCI Journal of the National Cancer Institute (2004)

The results of the well-conducted trial by Saad et al. (1) have prompted many to consider routine use of zoledronic acid to reduce the incidence of skeletal-related events in minimally symptomatic or asymptomatic men with hormone-refractory prostate cancer.This is a somewhat troublesome proposition, because all men in this situation are not at risk of a skeletal-related event.In the placebo arm of the trial (1), the rate of skeletal-related events was 44.2%, and thus more than half the men participating in the trial never experienced a skeletal-related event.Higher rates of fatigue, anemia, myalgia, fever, lower limb edema, dizziness, and weight loss were reported by men who received zoledronic acid than by men who received placebo.Thus, there is a good rationale for avoiding this treatment in men at little risk for a skeletal-related event.Uni-and multivariable analyses of baseline patient characteristics and treatment received are usually included in reports of large, randomized trials.Typically these analyses identify independent predictors of the primary outcome and adjust the treatment effect for chance imbalances in these predictors, increasing the precision of the treatment effect (2).Compared with men who received placebo, men who received zoledronic acid at 4 mg had fewer prior skeletal-related events (30.8% versus 37.5%) and had longer median survival (546 days versus 464 days), suggesting subtle differences between these groups at baseline that may have influenced the
Very Small<i>P</i>Values
Authors: Thomas R. Knapp, Matthew J. Hayat
Journal: JAMA Psychiatry (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Contact screening in tuberculosis: can we identify those with higher risk?: Table 1–
Authors: Maria Aurora Mendes, Rita Gaio, Ricardo Reis, Raquel Duarte
Journal: European Respiratory Journal (2013)

Contact screening in tuberculosis: can we identify those with higher risk?To the Editor:Contact screening, as a strategy to identify recently infected individuals, is part of the tuberculosis (TB) elimination strategy.It follows risk stratification concerning the infectiousness of the index patient, the duration and proximity of exposure, and the susceptibility of the contact [1, 2].For its optimisation it is important to know which risk factors are associated with Mycobacterium tuberculosis transmission in order to not over screen or lose at-risk contacts.In view of that, this study aims to identify potential risk factors for M. tuberculosis transmission among contacts of pulmonary TB patients, in a Portuguese TB reference centre.From January to December of 2011, all contacts of confirmed pulmonary TB patients, screened in the TB centre, were questioned about their exposure to the index patient through a questionnaire completed during the medical appointment.Both household and casual contacts were screened, independent of their cumulative exposure.Contacts excluded: those with exposure outdoors (e.g. in the street); those with incomplete characterisation of exposure (e.g.index patients for whom we did not know the symptomatic period); those non-compliant with screening (e.g.contacts who failed tuberculin skin test (TST) reading); and those with a past history of M. tuberculosis infection or TB disease (e.g.contacts verbal report of previous TB disease, contact with a pulmonary TB patient or treatment for latent tuberculosis infection (LTBI)).
ANA-negative systemic lupus erythematosus
Authors: K.C. NOZ
Journal: British Journal of Dermatology (1993)

Journal Article ANA–negative systemic lupus erythematosus Get access K.C. NOZ K.C. NOZ Department of Dermatology, Leiden University Hospital The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 3, 1 September 1993, Pages 345–346, https://doi.org/10.1111/j.1365-2133.1993.tb11866.x Published: 01 September 1993
Meeting the Governance Challenges of Next-Generation Biorepository Research
Authors: Stephanie M. Fullerton, Nicholas R. Anderson, Greg Guzauskas, Dena Freeman, Kelly Fryer-Edwards
Journal: Science Translational Medicine (2010)

Advances in clinical translational research have led to an explosion of interest in infrastructure development and data sharing facilitated by biorepositories of specimens and linked health information. These efforts are qualitatively different from the single-center sample collections that preceded them and pose substantial new ethics and regulatory challenges for investigators and institutions. New research governance approaches, which can address current and anticipated challenges, promote high-quality research, and provide a robust basis for ongoing research participation, are urgently required.
Association of age, sex and deprivation with quality indicators for diabetes: population-based cross sectional survey in primary care
Authors: J. Gray, C. Millett, C. O'Sullivan, R. Z Omar, A. Majeed
Journal: Journal of the Royal Society of Medicine (2006)

ObjectivesTo determine the quality of diabetes management in primary care after the publication of the National Service Framework and examine the impact of age, gender and deprivation on the achievement of established quality indicators. DesignPopulation-based cross sectional survey using electronic general practice records carried out between June–October 2003. Participants6035 adult patients (≥18 years) with diabetes from a total registered population of 201 572 patients. Main Outcome MeasuresSuccess rates for the diabetes quality indicators within the General Medical Services contract for general practitioners. ResultsWe identified large variations in diabetes management between general practitioner practices with poorer recording of quality care in younger patients (18–44 years). In addition, younger patients had a worse cholesterol and glycaemia profile, although hypertension was more common in older patients. Gender and deprivation did not appear to be important determinants of the quality of care received. ConclusionsThere are large variations in diabetes management between general practitioner practices, with care seemingly worse for younger adults. Longitudinal studies are required to determine whether current UK quality improvement initiatives have been successful in attenuating existing variations in care and treatment outcomes.
Septic Arthritis Due to Pseudomonas aeruginosa
Authors: Jerry R. Tindel
Journal: JAMA (1971)

Two patients had septic arthritis due to<i>Pseudomonas aeruginosa</i>. In one a heroin addict, the sternoclavicular joint was involved. The detection of precipitating antibodies to<i>Pseudomonas</i>led to the diagnosis of<i>Pseudomonas</i>arthritis. The infection was cured by surgical drainage and gentamicin sulfate therapy. The knee was involved in the second patient by spread into the joint from contiguous cellulitis or thrombophlebitis. The infection was not suppressed by parenteral administration of polymyxin B sulfate alone but was suppressed by parenterally and intraarticularly administered polymyxin and later by parenterally and intra-articularly administered gentamicin. Amputation was eventually required for cure of the infection.<i>Pseudomonas</i>is an unusual cause of septic arthritis, being found in only 2% of patients of a combined series. In treatment of<i>Pseudomonas</i>arthritis with either polymyxin or gentamicin, both parenterally and intra-articularly administered antibiotic should be used.