tbuckley/cabot-search huggingface dataset:
Particulate Matter Air Pollution and Cardiovascular Disease
Authors: Robert D. Brook, Sanjay Rajagopalan, C. Arden Pope, Jeffrey R. Brook, Aruni Bhatnagar, Ana V. Diez-Roux, Fernando Holguin, Yuling Hong, Russell V. Luepker, Murray A. Mittleman, Annette Peters, David Siscovick, Sidney C. Smith, Laurie Whitsel, Joel D. Kaufman
Journal: Circulation (2010)

In 2004, the first American Heart Association scientific statement on “Air Pollution and Cardiovascular Disease” concluded that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality. In the interim, numerous studies have expanded our understanding of this association and further elucidated the physiological and molecular mechanisms involved. The main objective of this updated American Heart Association scientific statement is to provide a comprehensive review of the new evidence linking PM exposure with cardiovascular disease, with a specific focus on highlighting the clinical implications for researchers and healthcare providers. The writing group also sought to provide expert consensus opinions on many aspects of the current state of science and updated suggestions for areas of future research. On the basis of the findings of this review, several new conclusions were reached, including the following: Exposure to PM &lt;2.5 μm in diameter (PM 2.5 ) over a few hours to weeks can trigger cardiovascular disease–related mortality and nonfatal events; longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within more highly exposed segments of the population by several months to a few years; reductions in PM levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM 2.5 exposure and cardiovascular morbidity and mortality. This body of evidence has grown and been strengthened substantially since the first American Heart Association scientific statement was published. Finally, PM 2.5 exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality.
T cell development in B cell-deficient mice. II. Serological characterization of suppressor T cell factors (TsF1) produced in normal mice and in mice treated chronically with rabbit anti-mouse IgM antibodies.
Authors: M S Sy, K T Hayglass, B Benacerraf
Journal: The Journal of Experimental Medicine (1985)

Serological analysis of idiotypic specificities present in azobenzenearsonate (ABA)-specific first-order suppressor T cell factors (TsF1) from C.AL-20 and BALB/c mice revealed a significant difference between TsF from these two strains of mice. The idiotypic composition of TsF1 from BALB/c mice appears to be more heterogeneous, and at least two different fractions can be readily identified. One bears the characteristic BALB/c-associated CRI(C) (crossreactive idiotype) determinants, and the other is non-CRI(C)-bearing. Analysis of ABA-specific TsF1 from animals lacking B cells uncovered a fundamental change in the expression of their idiotypic specificities. TsF from rabbit anti-mouse IgM (anti-mu)-treated C.AL-20 mice failed to express the characteristic CRI(A) determinants. Instead, they express CRI(C) specificities. Similarly, TsF1 from anti-mu-treated BALB/c mice did not express their characteristic CRI(C) specificities, but rather express CRI(A) determinants. These experiments provide strong evidence that the Igh restriction specificity of TsF is dictated by the particular idiotypic specificities expressed. They also clearly demonstrate that B cells and their products play an important role in establishing the idiotypic composition and repertoire of suppressor T cells.
Recurrent Somatic<i>DICER1</i>Mutations in Nonepithelial Ovarian Cancers
Authors: Alireza Heravi-Moussavi, Michael S. Anglesio, S.-W. Grace Cheng, Janine Senz, Winnie Yang, Leah Prentice, Anthony P. Fejes, Christine Chow, Alicia Tone, Steve E. Kalloger, Nancy Hamel, Andrew Roth, Gavin Ha, Adrian N.C. Wan, Sarah Maines-Bandiera, Clara Salamanca, Barbara Pasini, Blaise A. Clarke, Anna F. Lee, Cheng-Han Lee, Chengquan Zhao, Robert H. Young, Samuel A. Aparicio, Poul H.B. Sorensen, Michelle M.M. Woo, Niki Boyd, Steven J.M. Jones, Martin Hirst, Marco A. Marra, Blake Gilks, Sohrab P. Shah, William D. Foulkes, Gregg B. Morin, David G. Huntsman
Journal: New England Journal of Medicine (2011)

Germline truncating mutations in DICER1, an endoribonuclease in the RNase III family that is essential for processing microRNAs, have been observed in families with the pleuropulmonary blastoma-family tumor and dysplasia syndrome. Mutation carriers are at risk for nonepithelial ovarian tumors, notably sex cord-stromal tumors.We sequenced the whole transcriptomes or exomes of 14 nonepithelial ovarian tumors and noted closely clustered mutations in the region of DICER1 encoding the RNase IIIb domain of DICER1 in four samples. We then sequenced this region of DICER1 in additional ovarian tumors and in certain other tumors and queried the effect of the mutations on the enzymatic activity of DICER1 using in vitro RNA cleavage assays.DICER1 mutations in the RNase IIIb domain were found in 30 of 102 nonepithelial ovarian tumors (29%), predominantly in Sertoli-Leydig cell tumors (26 of 43, or 60%), including 4 tumors with additional germline DICER1 mutations. These mutations were restricted to codons encoding metal-binding sites within the RNase IIIb catalytic centers, which are critical for microRNA interaction and cleavage, and were somatic in all 16 samples in which germline DNA was available for testing. We also detected mutations in 1 of 14 nonseminomatous testicular germ-cell tumors, in 2 of 5 embryonal rhabdomyosarcomas, and in 1 of 266 epithelial ovarian and endometrial carcinomas. The mutant DICER1 proteins had reduced RNase IIIb activity but retained RNase IIIa activity.Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in nonepithelial ovarian tumors. These mutations do not obliterate DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic. (Funded by the Terry Fox Research Institute and others.).
Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer
Authors: J.W.G. van Putten, T. Kerbush, E.F. Smit, R. van Rijswijk, J.H. Beijnen, D.T. Sleijfer, H.J.M. Groen
Journal: Annals of Oncology (2001)
Regulation of Vascular Endothelial Growth Factor in Cardiac Myocytes
Authors: Andrew P. Levy, Nina S. Levy, Joseph Loscalzo, Angelino Calderone, Nobuyuki Takahashi, Kiang-Teck Yeo, Gideon Koren, Wilson S. Colucci, Mark A. Goldberg
Journal: Circulation Research (1995)

Collateral blood vessels supplement normal coronary blood flow and coronary blood flow compromised by coronary artery disease, thereby protecting the myocardium from ischemia. Collateral vessel formation is the result of angiogenesis. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a secreted mitogen specific for endothelial cells and an extremely potent angiogenic factor. In the present study, VPF/VEGF mRNA and protein were demonstrated to be markedly stimulated in primary rat cardiac myocytes in vitro in response to reduction of the oxygen tension to 1% or inhibition of the electron transport chain. Four isoforms of VPF/VEGF were coordinately regulated by hypoxia, including a novel isoform not previously described. Phorbol ester and the depolarizing agent veratridine, stimulators of protein kinase C and calcium influx, respectively, were found to markedly increase VPF/VEGF mRNA expression in cardiac myocytes. Forskolin, a potent stimulator of adenylate cyclase, produced a small but significant increase in VPF/VEGF mRNA expression in the cardiac myocytes. However, only H7, an inhibitor of protein kinase C, inhibited the hypoxic induction of VPF/VEGF mRNA; inhibitors of calcium influx and the calcium-calmodulin-dependent protein kinase II as well as inhibition of protein kinase A did not block the hypoxic induction of VPF/VEGF mRNA. This suggests that more than one signal transduction pathway is involved in regulating VPF/VEGF expression. The sensor that regulates the expression of hypoxia-responsive genes has been proposed to be a heme protein. Consistent with this model, transition metals initiate a genetic program similar to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Child-focused state cash transfers and adolescent risk of HIV infection in South Africa: a propensity-score-matched case-control study
Authors: Lucie Cluver, Mark Boyes, Mark Orkin, Marija Pantelic, Thembela Molwena, Lorraine Sherr
Journal: The Lancet Global Health (2013)

Effective and scalable HIV prevention for adolescents in sub-Saharan Africa is needed. Cash transfers can reduce HIV incidence through reducing risk behaviours. However, questions remain about their effectiveness within national poverty-alleviation programmes, and their effects on different behaviours in boys and girls.In this case-control study, we interviewed South African adolescents (aged 10-18 years) between 2009 and 2012. We randomly selected census areas in two urban and two rural districts in two provinces in South Africa, including all homes with a resident adolescent. We assessed household receipt of state-provided child-focused cash transfers, incidence in the past year and prevalence of transactional sex, age-disparate sex, unprotected sex, multiple partners, and sex while drunk or after taking drugs. We used logistic regression after propensity score matching to assess the effect of cash transfers on these risky sexual behaviours.We interviewed 3515 participants (one per household) at baseline, and interviewed 3401 at follow-up. For adolescent girls (n=1926), receipt of a cash transfer was associated with reduced incidence of transactional sex (odds ratio [OR] 0·49, 95% CI 0·26-0·93; p=0·028), and age-disparate sex (OR 0·29, 95% CI 0·13-0·67; p=0·004), with similar associations for prevalence (for transactional sex, OR 0·47, 95% CI 0·26-0·86; p=0·015; for age-disparate sex, OR 0·37, 95% CI 0·18-0·77; p=0·003). No significant effects were shown for other risk behaviours. For boys (n=1475), no consistent effects were shown for any of the behaviours.National, child-focused cash transfers to alleviate poverty for households in sub-Saharan Africa can substantially reduce unsafe partner selection by adolescent girls. Child-focused cash transfers are of potential importance for effective combination strategies for prevention of HIV.UK Economic and Social Research Council, South African National Research Foundation, Health Economics and AIDS Research Division at University of KwaZulu-Natal, South African National Department of Social Development, Claude Leon Foundation, John Fell Fund, Nuffield Foundation, and Regional Interagency Task Team for Children affected by AIDS-Eastern and Southern Africa.
Somatic Mutations Predict Poor Outcome in Patients With Myelodysplastic Syndrome After Hematopoietic Stem-Cell Transplantation
Authors: Rafael Bejar, Kristen E. Stevenson, Bennett Caughey, R. Coleman Lindsley, Brenton G. Mar, Petar Stojanov, Gad Getz, David P. Steensma, Jerome Ritz, Robert Soiffer, Joseph H. Antin, Edwin Alyea, Philippe Armand, Vincent Ho, John Koreth, Donna Neuberg, Corey S. Cutler, Benjamin L. Ebert
Journal: Journal of Clinical Oncology (2014)

Recurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known.We used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.Mutations were identified in 92% of patients, most frequently in the ASXL1 (29%), TP53 (21%), DNMT3A (18%), and RUNX1 (16%) genes. In univariable analyses, only TP53 mutations were associated with shorter overall (OS; hazard ratio [HR], 3.74; P < .001) and progression-free survival (HR, 3.97; P < .001). After adjustment for clinical variables associated with these end points, mutations in TP53 (HR, 2.30; P = .027), TET2 (HR, 2.40; P = .033), and DNMT3A (HR, 2.08; P = .049) were associated with decreased OS. In multivariable analysis including clinical variables, complex karyotype status, and candidate genes, mutations in TP53 (HR, 4.22; P ≤ .001) and TET2 (HR, 1.68; P = .037) were each independently associated with shorter OS. Nearly one half of patients (46%) carried a mutation in TP53, DNMT3A, or TET2 and accounted for 64% of deaths. Three-year OS in patients without these mutations was 59% (95% CI, 43% to 72%), versus 19% (95% CI, 9% to 33%) in patients with these mutations.Mutations in TP53, TET2, or DNMT3A identify patients with MDS with shorter OS after HSCT.
Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration
Authors: S. E Steer, F. M K Williams, B. Kato, J. P Gardner, P. J Norman, M. A Hall, M. Kimura, R. Vaughan, A. Aviv, T. D Spector
Journal: Annals of the Rheumatic Diseases (2006)

Rheumatoid arthritis (RA) is associated with reduced lifespan and shortened telomere length in lymphocytes, but the mechanism underlying this is unclear. Telomere loss in white blood cells (WBC) is accelerated by oxidative stress and inflammation in vitro. It was postulated that the accelerated WBC telomere shortening in RA occurs as a result of exposure to chronic inflammation.To measure telomere terminal restriction fragment (TRF) length in a large cohort of RA cases and healthy controls, to explore associations of TRF length with features of disease and with RA-associated HLA-DRB1 alleles.WBC and TRF length were measured by Southern blot in DNA from 176 hospital-based RA cases satisfying the 1987 American College of Rheumatology criteria and from 1151 controls. TRF length was compared between cases and controls, and the effects of disease duration, severity and HLA-DRB1 alleles encoding the shared epitope (SE) were assessed.Age- and sex-adjusted TRF length was significantly shorter in RA cases compared with controls (p<0.001). There was no association between age- and sex-adjusted TRF length and disease duration, C reactive protein or Larsen score. The presence of one or more SE-encoding alleles was associated with reduced adjusted TRF length in RA cases (SE positive vs SE negative cases, p=0.038), but not in controls.The reduced TRF length in a large group of patients with RA compared with controls has been shown. The reduction is apparently independent of disease duration and markers of disease severity, but is influenced by HLA-DRB1 genotype.
Low incidence of Epstein-Barr virus presence in primary cutaneous T-cell lymphoproliferations
Authors: I. ANAGNOSTOPOULOS., M. HUMMEL., P. KAUDEWITZ, P. KORBJUHN, L. LEONCINI, H. STEIN
Journal: British Journal of Dermatology (1996)

Multiple biopsies taken from 76 European human immunodeficiency virus (HIV)-negative patients with primary cutaneous T-cell lymphoproliferations, including mycosis fungoides (MF), pleomorphic T-cell lymphoma (PMTCL), anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis (LyP) were investigated for the presence of Epstein-Barr virus (EBV) through a combined approach. Polymerase chain reaction (PCR) was employed for EBV-DNA detection, in situ hybridization (ISH) for cellular localization of EBV-encoded nuclear RNAs (EBER1 and EBER2) and immediate early Bam H-fragment; lower frame (BHLF) RNA, and immunohistology (IH) for the identification of EBV-encoded latent membrane protein 1 (LMP1) and of nuclear antigen (EBNA) 2 expression. EBV-DNA was detectable by PCR in 15 of 76 cases (19.7%). EBER-ISH combined with IH identified a variable, usually very low, number of infected neoplastic cells in only seven of the 15 EBV-DNA-harbouring cases. This discrepancy between the results obtained with PCR and ISH is apparently caused by the low number of the infected cells per tissue section. The PMTCL entity produced the greatest number of positive cases, whilst ALCL and LyP cases were almost constantly devoid of the virus. BHLF transcripts were not detectable in any case, nor did any of the EBER-positive cells show an LMP1 or EBNA2 expression. These data show that primary cutaneous T-cell lymphoproliferations display an infrequent association with a latent EBV infection and that the pathogenic role of the virus in the positive cases remains obscure as the virus frequently infects only a minority of the atypical cells.
Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma
Authors: H. L. Kaufman
Journal: Journal of Clinical Investigation (2005)

Immunotherapy for the treatment of metastatic melanoma remains a major clinical challenge. The melanoma microenvironment may lead to local T cell tolerance in part through downregulation of costimulatory molecules, such as B7.1 (CD80). We report the results from the first clinical trial, to our knowledge, using a recombinant vaccinia virus expressing B7.1 (rV-B7.1) for monthly intralesional vaccination of accessible melanoma lesions. A standard 2-dose-escalation phase I clinical trial was conducted with 12 patients. The approach was well tolerated with only low-grade fever, myalgias, and fatigue reported and 2 patients experiencing vitiligo. An objective partial response was observed in 1 patient and disease stabilization in 2 patients, 1 of whom is alive without disease 59 months following vaccination. All patients demonstrated an increase in postvaccination antibody and T cell responses against vaccinia virus. Systemic immunity was tested in HLA-A*0201 patients who demonstrated an increased frequency of gp100 and T cells specific to melanoma antigen recognized by T cells 1 (MART-1), also known as Melan-A, by ELISPOT assay following local rV-B7.1 vaccination. Local immunity was evaluated by quantitative real-time RT-PCR, which suggested that tumor regression was associated with increased expression of CD8 and IFN-gamma. The local delivery of vaccinia virus expressing B7.1 was well tolerated and represents an innovative strategy for altering the local tumor microenvironment in patients with melanoma.
Addition of Sirolimus to Cyclosporine Delays the Recovery from Delayed Graft Function but Does not Affect 1-Year Graft Function
Authors: Giovanni Stallone, Salvatore Di Paolo, Antonio Schena, Barbara Infante, Michele Battaglia, Pasquale Ditonno, Loreto Gesualdo, Giuseppe Grandaliano, Francesco Paolo Schena
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Delayed graft function (DGF) has long been identified as one of the main correlates of poor graft survival in cadaveric renal transplantation, but the factors that affect its onset and duration are not fully elucidated. The impact of two immunosuppressive protocols on the incidence and length of DGF among kidney transplant recipients of a suboptimal organ was evaluated. Patients were randomly treated with corticosteroids (CS); low-dose cyclosporine (CsA) and sirolimus (SRL; group 1; n = 42); or CS, full-dose CsA, and mycophenolate mofetil (group 2; n = 48). All recipients received immunoprophylaxis with basiliximab. After 3 mo, group 1 discontinued CsA and continued with SRL, whereas group 2 continued the same treatment. The incidence of DGF was similar in the two groups (group 1 = 52.4%; group 2 = 58.3%), whereas its duration was significantly higher in the group 1 (19.0 ± 6.0 versus 10.3 ± 3.2 d; P = 0.001). Both groups showed 100% actuarial graft and patient survival at 1-yr. Among DGF patients, serum creatinine (sCr) at discharge was significantly worse in group 1 (sCr, 3.0 ± 1.0 versus 1.5 ± 0.2 mg/dl; calculated creatinine clearance, 31.2 ± 9.3 versus 61.1 ± 10 ml/min; P = 0.001). During the first year, the former group displayed a significant improvement of graft function, such that at 1-yr, no difference could be measured between groups (sCr, 1.8 ± 0.5 versus 1.7 ± 0.4 mg/dl; calculated creatinine clearance, 51.5 ± 10.2 versus 53.3 ± 9.4 ml/min). In conclusion, in de novo renal transplanted patients, the administration of SRL, in combination with low-dose CsA, is associated with a delayed recovery from DGF but does not worsen 1-yr graft function. E-mail: [email protected]
Relationship Between Antidepressants and Suicide Attempts: An Analysis of the Veterans Health Administration Data Sets
Authors: Robert D. Gibbons, C. Hendricks Brown, Kwan Hur, Sue M. Marcus, Dulal K. Bhaumik, J. John Mann
Journal: American Journal of Psychiatry (2007)

In late 2006, a U.S. Food and Drug Administration advisory committee recommended that the 2004 black box warning regarding suicidality in pediatric patients receiving antidepressants be extended to include young adults. This study examined the relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system.The authors analyzed data on 226,866 veterans who received a diagnosis of depression in 2003 or 2004, had at least 6 months of follow-up, and had no history of depression from 2000 to 2002. Suicide attempt rates overall as well as before and after initiation of antidepressant therapy were compared for patients who received selective serotonin reuptake inhibitors (SSRIs), new-generation non-serotonergic-specific (non-SSRI) antidepressants (bupropion, mirtazapine, nefazodone, and venlafaxine), tricyclic antidepressants, or no antidepressant. Age group analyses were also performed.Suicide attempt rates were lower among patients who were treated with antidepressants than among those who were not, with a statistically significant odds ratio for SSRIs and tricyclics. For SSRIs versus no antidepressant, this effect was significant in all adult age groups. Suicide attempt rates were also higher prior to treatment than after the start of treatment, with a significant relative risk for SSRIs and for non-SSRIs. For SSRIs, this effect was seen in all adult age groups and was significant in all but the 18-25 group.These findings suggest that SSRI treatment has a protective effect in all adult age groups. They do not support the hypothesis that SSRI treatment places patients at greater risk of suicide.
Do House Officers Learn From Their Mistakes?
Authors: Albert W. Wu
Journal: JAMA (1991)

Mistakes are inevitable in medicine. To learn how medical mistakes relate to subsequent changes in practice, we surveyed 254 internal medicine house officers. One hundred fourteen house officers (45%) completed an anonymous questionnaire describing their most significant mistake and their response to it. Mistakes included errors in diagnosis (33%), prescribing (29%), evaluation (21%), and communication (5%) and procedural complications (11%). Patients had serious adverse outcomes in 90% of the cases, including death in 31% of cases. Only 54% of house officers discussed the mistake with their attending physicians, and only 24% told the patients or families. House officers who accepted responsibility for the mistake and discussed it were more likely to report constructive changes in practice. Residents were less likely to make constructive changes if they attributed the mistake to job overload. They were more likely to report defensive changes if they felt the institution was judgmental. Decreasing the work load and closer supervision may help prevent mistakes. To promote learning, faculty should encourage house officers to accept responsibility and to discuss their mistakes. (<i>JAMA</i>. 1991;265:2089-2094)