tbuckley/cabot-search huggingface dataset:
Is It I
Authors: Donna Pucciani
Journal: JAMA (2005)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 19309: What is the Impact of Transcatheter Aortic Valve Implantation on Patients' Profile and on Outcomes of Aortic Valve Surgery Programs? A Multi-Institutional Appraisal
Authors: Augusto D'Onofrio, Ottavio Alfieri, Francesco Alamanni, Melissa Fusari, Vincenzo Tarzia, Giulio Rizzoli, Gino Gerosa
Journal: Circulation (2012)

Objective: Aim of this retrospective multicenter study was to assess how the introduction of transcatheter aortic valve implantation (TAVI) influenced the characteristics and the outcomes of patients undergoing aortic valve procedures. Methods: We analyzed data from 1395 patients who underwent isolated surgical aortic valve replacement (SAVR) or TAVI in 3 centers with a high-volume TAVI program. We considered two different time periods: “Pre-TAVI”, 395 patients (28.3%) operated on before the introduction of TAVI and “Post-TAVI”, 1000 patients (71.7%) operated on after the introduction of TAVI into clinical practice. We evaluated patients’ age, preoperative risk stratification (logistic Euroscore) and hospital mortality according to time periods and to the procedure performed. Results: “Post-TAVI” patients were older (78.2±7.8 vs 76.8±6.7 years; p=0.002) and with a significantly higher risk profile (Logistic Euroscore: 17.8±14.7% vs 9.1±9.2%; p&lt;0.001) when compared to “Pre-TAVI” patients. However, hospital mortality was not significantly different between groups (“Pre-TAVI”: 8 patients, 2% vs “Post-TAVI”: 34 patients, 3.4%; p=0.17). Out of the 1000 “Post-TAVI” period patients, 605 (60.5%) underwent TAVI and 395 (39.5%) underwent SAVR. Patients undergoing TAVI were older (79.9±7.1 vs 75.5±9.2 years; p&lt;0.001) and had a higher Euroscore (22.9±15.3% vs 9.7±9.3%) than “Post-TAVI” SAVR patients but their hospital mortality was similar (24 patients, 3.9% vs 10 patients, 2.5%; p=0.22). Preoperative risk stratification was similar between “Pre-TAVI” and “Post-TAVI” SAVR patients (9.1±9.2% vs 9.7±9.3%; p=0.26). Furthermore, we did not find significant differences in the overall hospital mortality between SAVR and TAVI patients: 18 patients, 2.3% vs 24 patients, 3.9%, p=0.08. Conclusions: The development of TAVI has determined an increase of preoperative risk profile of patients scheduled for aortic valve procedures (SAVR or TAVI) without increasing hospital mortality. TAVI patients were older and with higher Euroscore than SAVR patients but hospital mortality was similar. Therefore these data justify the introduction of TAVI into routine practice since it allows treatment of high risk patients without an adverse impact on mortality.
Removal of CD25+ cells from precursor alloreactive cytotoxic T lymphocyte preparations does not prevent T regulatory cell generation after the one-way mixed lymphocyte reaction
Authors: Michelle Hickey, Amy Lin, Carol Kruse
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

265 

An effector cell population, alloreactive cytotoxic T lymphocytes (aCTL), sensitized to human leukocyte antigens (HLA) of the tumor host, has shown promise when intratumorally instilled into the resected tumor beds of recurrent gliomas. Half of the six patients treated in a pilot study responded. We hypothesized that the removal of T regulatory (Treg) cells from the precursor aCTL preparations may further optimize the therapy, or perhaps help to explain the nonresponse observed in 3 of the 6 patients. Treg cells are a subset of CD4+ T cells expressing the activation marker CD25 (IL-2 receptor α-chain); they also can express FoxP3, a member of the Forkhead box/winged-helix family of transcriptional regulators. Treg cells normally constitute a low percentage (0.5-6.0%) of peripheral blood mononuclear cells (PBMC) and therefore are a small entity within the normal donor PBMC used as precursor aCTL. A simple magnetic bead removal of the Treg cell compartment from the PBMC could be easily implemented during clinical generation of aCTL. Therefore, we tested to see if the batch removal of CD25+ cells from the PBMC (precursor aCTL) would improve the growth kinetics and cytolytic function of aCTL. Our preliminary data show that the frequency of Treg cells present in PBMC pools increases during culture of the aCTL after performing the one-way mixed lymphocyte reaction (MLR). Dual positive CD4+FoxP3+ Treg cells were found to comprise approximately 1% of the CD4+ T cell population in the PBMC used as precursor aCTL, and by day 14 post-MLR, the frequency of Treg cells increased up to 5-fold. aCTL preparations made from PBMC lacking CD25+ T cells (aCTL-CD25) were mixed with inactivated stimulator lymphoblasts at a 10:1 responder to stimulator ratio, and compared to parallel aCTL cultures that were not depleted of CD25+ cells. Growth rate, measured by daily lactate production, was similar throughout a 14 day culture period. Surprisingly, the cytotoxic capability of aCTL-CD25 was significantly inhibited ( p <0.001) compared to that of CD25-undepleted aCTL. We additionally observed that the percentages of CD4+/FoxP3+ cells in the aCTL-CD25 cultures were consistently higher on day 14 post-MLR compared to the percentages seen in the undepleted cultures. The data indicate that despite batch removal of CD25+ cells from precursor aCTL, the cytolytic function of aCTL was not improved, and in fact, resulted in an increased population of CD4+FoxP3+ Treg cells.
Phase III trial of adjuvant 13- cis -retinoic acid and interferon-alpha for patients with aggressive skin squamous cell carcinoma.
Authors: Abenaa M. Brewster, J. Jack Lee, Gary Clayman, John Clifford, Mary Jo Necesito Reyes, Xian Zhou, Anita Sabichi, Sara Strom, Robert Collins, Christina Meyers, Scott Lippman
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5659 

A phase III trial was conducted to evaluate the efficacy of adjuvant 13- cis -retinoic acid (13cRA) plus interferon-alpha (IFN-alpha) for increasing the time to recurrence and preventing second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC. From 1996 to 2002, 66 patients with aggressive skin SCC were randomly assigned to receive either combined 13cRA (1 mg/kg/day orally) and IFN-alpha (3 × 106 units subcutaneously three times per week) for 6 months or no adjuvant therapy following SCC surgery and/or radiation. At a median of 21.5 months of follow-up, treatment did not improve the time to recurrence plus SPT (versus no treatment) (hazard ratio, 1.13; 95% confidence interval, 0.53–2.41) or time to tumor recurrence (hazard ratio, 1.08; 95% confidence interval, 0.43–2.72) or time to SPT (hazard ratio, 0.89; 95% confidence interval, 0.27–2.93). Adjuvant 13cRA and IFN-alpha was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities. This study does not support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. The high rates of tumor recurrence and SPTs remain an unmet medical challenge with devastating consequences for patients with this disease. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.
Abstract 4853: Association of Physician Certification with Rates of CRT-D Implantation in Eligible Patients: Insights from the ICD Registry
Authors: Jeptha P Curtis, Jeffrey Leubbert, Yongfei Wang, Rachel Lampert, Saif S Rathore, Stephen Hammill, Paul Heidenreich, Harlan M Krumholz
Journal: Circulation (2008)

Current guidelines recommend cardiac resynchronization therapy (CRT-D) in appropriate patients undergoing ICD implantation. However, not all physicians who implant ICDs are trained to perform CRT-D. We examined the ICD Registry to assess whether use of CRT-D implantation varied by physician certification. We determined the certification of 2128 physicians who had submitted &gt;=10 cases between April 2006 and June 2007. We excluded patients with a prior ICD, an epicardial lead, or aged ≤18 years, leaving 111,293 patients. Physicians were grouped into mutually exclusive categories reflecting highest current certification- Electrophysiology (EP), Cardiovascular Disease (CVD), Thoracic Surgery (TS), Internal Medicine (IM), Heart Rhythm Society alternative pathway (HRS), and Other. Patients were considered eligible for CRT-D if they met the following criteria: QRS duration &gt;=120ms, LVEF ≪26&gt;35%, and NYHA Class III-IV. We examined crude rates of CRT-D across physician categories and developed a logistic regression model to assess the association of physician certification and CRT-D implantation. Candidate variables included demographics, cardiac status, comorbidities, and physician volume. Odds ratios were converted to relative risks. 35,851 patients met all three eligibility criteria for CRT-D, and 28,932 (80.7%) had a CRT-D implanted. EP physicians implanted the majority of CRT-D (73.6%), with fewer CRT-D placed by CVD (20.6%), TS (0.9%), IM (0.8%), HRS (1.1%), or Other (3.1%). The crude rate of CRT-D implantation was highest among EP physicians and lower in all other categories: EP- 83.1%, CVD-75.8%, TS- 57.9%, IM- 76.5%, HRS- 77.1%, Other- 73.5% (p&lt;0.001). In multivariable analysis, CVD and TS physicians were less likely to implant CRT-D in eligible patients compared with EP physicians (EP: Ref; CVD: RR 0.92 (0.90 – 0.94); TS: RR 0.76 (0.71– 0.85)). CRT-D rates were comparable for other physician groups (IM RR 0.95 (0.87–1.01); HRS: RR 0.97 (0.90 –1.02); Other RR 0.97 (0.93–1.00)). Among eligible patients, use of CRT-D varies by physician certification. Given the benefits of CRT-D, clinicians should consider referring eligible patients to physicians with familiarity and expertise in CRT-D implantation.
Autocrine signaling by PSA in prostate cancer cells
Authors: Thomas Nicotera, Mustapha Bourhim, David Schuster, Kailash Chadha
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4401 

PSA is an important biomarker for diagnosis of and prognosis assessment in prostate cancer. We have previously demonstrated that calcium-independent PLA2 (iPLA2) controls the secretion of PSA and inhibition of iPLA2 causes apoptosis in LNCaP cells. Addition of the PLA2 product arachidonic acid or its eicosanoid derivatives had no discernable effect on iPLA2-mediated apoptosis in LNCaP cells. However, addition of PSA together with iPLA2 inhibitor restored survival and addition of neutralizing antibody to PSA resulted in apoptosis. Addition of neutralizing antibody alone to LNCaP cells is sufficient to cause activation of caspases, indicative of apoptosis. Based on these data, we hypothesized that PSA plays an autocrine role that affects the survival of prostate cancer cells. Since the PI3K/Akt pathway plays a major role in prostate cancer cell survival, we tested whether PSA could activate the PI3K/Akt. Investigation of PSA signaling by western analysis shows that PSA causes the activation of Akt through phosphorylation at both Ser-473 and Thr-308 in LNCaP cells in a dose and time-dependent fashion. Phosphorylation of Akt was initiated within 2 hr by PSA at concentrations between 200 and 700 ng/ml and incubation at 3 hr required 25 to 200 ng/ml PSA. Treatment with PI3K inhibitors LY294002 and wortmannin in combination with PSA completed inhibited Akt activation. These data indicate that PSA participates in autocrine signaling that contributes to the regulation of survival of prostate cancer cells. While PSA is one of the best biomarkers for the early detection of any cancer, its effect on patient survival is under question. A role for PSA in cancer progression could explain its minimal impact on patient survival while acting as an early warning signal for the disease.
DSM-IV and new diagnostic categories: holding the line on proliferation
Authors: Harold A. Pincus, Allen Frances, Wendy W. Davis, Michael B. First, Thomas A. Widiger
Journal: American Journal of Psychiatry (1992)

The authors discuss aspects of the decision-making process for including "new" diagnostic categories in DSM-IV. They detail the different kinds of new categories proposed for inclusion in DSM-IV and discuss the risks and benefits of incorporating them. The authors comment on whether new diagnostic categories should be included in official nosologies as a stimulus for research or as a culmination of research. They also highlight problems with "sunsetting" diagnoses. The criteria for change in DSM-IV--a way to deal with the expanding array of proposals for additional diagnostic entities--are discussed. The authors also offer a series of specific examples of the different kinds of new categories being considered for inclusion in DSM-IV.
圧負荷心肥大モデルラットにおいて1B型アンジオテンシンII受容体が媒介するトランスフォーミング増殖因子ベータ1(TGF‐ベータ1)の増加が引き起こす心筋線維化
Authors: Obata Je, Nakamura T, Naitoh A, Kimura H, Tamura K, Yoshida Y, Inagami T
Journal: Circulation (1996)
Human Antihapten Antibodies in Trimellitic Anhydride Inhalation Reactions
Authors: Roy Patterson, C. Raymond Zeiss, Mary Roberts, Jacob J. Pruzansky, Peter Wolkonsky, R. Chacon
Journal: Journal of Clinical Investigation (1978)

Inhalational exposure to trimellitic anhydride (TMA) produces an immediate-type asthmatic or a late respiratory systemic syndrome in certain workers after a latent period of work exposure. TMA has been found to react with proteins to produce a hapten-protein complex (trimellitate [TM] protein) or become hydrolyzed in aqueous, alkaline solutions to produce a salt, NaTM. Using a solid-phase radioimmunoassay technique, antibodies of different Ig classes were detected against TM-protein conjugates. IgE antibody was detected in three of five workers with asthma. IgG and IgA antibodies were detected in most exposed workers but higher levels of antibody were found in symptomatic workers even after long periods without direct TMA exposure. IgM antibody activity against TM-human serum albumin (TM-HSA) was detected but did not differentiate symptomatic from asymptomatic workers. NaTM served as a hapten for study because it does not react with proteins to form a hapten-protein complex as TMA does. The NaTM only partially inhibited IgG antibody activity against TM-HSA and much smaller amounts of TM-HSA than of NaTM were required to neutralize IgG antibody. A similar result was found with TM-ovalbumin. The latter results suggest that some IgG antibody is directed against a TM-protein moiety, probably a TM-amino acid determinant. In contrast to IgG, marked inhibition by NaTM of IgA and IgM antibody against TM-HSA was found in the sera studied.
Bisphenol A, Bisphenol S, and 4-Hydro​xyphenyl 4-Isopro​oxyphenyl​sulfone (BPSIP) in Urine and Blood of Cashiers
Authors: Kristina A. Thayer, Kyla W. Taylor, Stavros Garantziotis, Shepherd H. Schurman, Grace E. Kissling, Dawn Hunt, Brenda Herbert, Rebecca Church, Rachael Jankowich, Mona I. Churchwell, Richard C. Scheri, Linda S. Birnbaum, John R. Bucher
Journal: Environmental Health Perspectives (2015)

Bisphenol A (BPA) is a high-production-volume chemical associated with a wide range of health outcomes in animal and human studies. BPA is used as a developer in thermal paper products, including cash register receipt paper; however, little is known about exposure of cashiers to BPA and alternative compounds in receipt paper.We determined whether handling receipt paper results in measurable absorption of BPA or the BPA alternatives bisphenol S (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP).Cashiers (n = 77) and non-cashiers (n = 25) were recruited from the Raleigh-Durham-Chapel Hill region of North Carolina during 2011-2013. Receipts were analyzed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected ≤ 2 hr after completing a shift) were compared with pre-shift samples. Levels of these compounds in urine from cashiers were compared to levels in urine from non-cashiers.Each receipt contained 1-2% by weight of the paper of BPA, BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. The mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as to increase after a shift, but the mean post-shift concentrations were significantly higher than those in non-cashiers. BPSIP was detected more frequently in the urine of cashiers handling BPSIP receipts than in the urine of non-cashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently.Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP.Thayer KA, Taylor KW, Garantziotis S, Schurman SH, Kissling GE, Hunt D, Herbert B, Church R, Jankowich R, Churchwell MI, Scheri RC, Birnbaum LS, Bucher JR. 2016. Bisphenol A, bisphenol S, and 4-hydro​xyphenyl 4-isopro​oxyphenyl​sulfone (BPSIP) in urine and blood of cashiers. Environ Health Perspect 124:437-444; http://dx.doi.org/10.1289/ehp.1409427.
Circulating biomarkers of sunitinib in patients with unresectable hepatocellular carcinoma (HCC): Analysis of correlations with outcome and tumor imaging parameters
Authors: S. E. DePrimo, A. Cheng, S. Lanzalone, M. J. Lechuga, C. S. Harmon, X. Lin, E. Raymond, S. J. Faivre
Journal: Journal of Clinical Oncology (2008)

4593 Background: Sunitinib malate (SU) is a multikinase inhibitor with antitumor activity in patients (pts) with HCC (Faivre et al, ASCO 2007). To assess potential biomarkers of SU response, we investigated plasma levels of soluble (s) proteins (VEGF-A, VEGF-C, sVEGFR-2 and -3, and sKIT) with roles in angiogenesis and SU target pathways. Methods: Pts (n=37) received SU 50 mg/d for 4 wks on, 2 wks off, every 6 wks. Pre-dose plasma samples were obtained on days (D) 1, 14, and 28 of cycle (C) 1 and D1 and 28 of C2. Soluble protein levels were measured by ELISA. Baseline levels and changes from baseline were analyzed for association with efficacy measures (time to progression [TTP], overall survival [OS], objective response, and tumor density changes [Choi criteria]). Results: Plasma protein levels were modulated in most pts during treatment. By the end of C1, VEGF-A levels increased >3-fold relative to baseline; sVEGFR-2, -3 and sKIT levels decreased (↓) by ∼50%, 70%, and 30%, respectively. VEGF-C levels ↓ by 30% by end of C2. Pretreatment VEGF-C levels correlated with TTP and OS, with levels above the median (>822 pg/mL) associated with longer times (TTP, p=0.004; OS, p=0.05). Pretreatment VEGF-C levels were also significantly higher in pts with partial response or stable disease >3 months (n=14) vs pts with progressive disease (n=13; p=0.02). Pts with largest ↓ in sKIT (< median) at C1D14 had longer TTP (p=0.018); sKIT ↓ also correlated with response according to Choi criteria (p=0.012) and with higher tumor necrosis, based on volumetric measurement (p=0.02; n=21). Choi criteria response correlated with larger ↓ in sVEGFR-3 (p=0.005). Higher tumor necrosis correlated with larger increases in VEGF-A (p=0.03) and larger ↓ in sVEGFR-2 (p=0.036). Conclusions: In HCC pts, SU is associated with modulation of plasma proteins involved in VEGF and KIT pathways. Baseline VEGF-C exhibited the strongest correlation with outcome. Additional correlations between biomarkers and various measures of antitumor activity were observed. Analysis of these biomarkers in larger studies of SU in HCC may be warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
Unraveling the Function of <i>FTO</i> Variants
Authors: Clifford J. Rosen, Julie R. Ingelfinger
Journal: New England Journal of Medicine (2015)

Body-mass index (BMI), which represents a complex trait with high heritability, is a clinically relevant surrogate for obesity.1 Genomewide association studies have identified nearly 10,000 genetic polymorphisms in single-nucleotide variants (SNVs) associated with various human disorders and traits. However, approximately 90% of these variants are in genomic regions that do not map to coding regions and, therefore, do not directly affect protein synthesis or translation.2 However, risk-associated loci containing noncoding variants can alter gene expression by modulating the activity of neighboring cis-regulatory elements — that is, noncoding DNA sequences in or near a gene that can modify the expression . . .