tbuckley/cabot-search huggingface dataset:
Burkitt lymphoma risk in U.S. solid organ transplant recipients
Authors: Sam M. Mbulaiteye, Christina A. Clarke, Lindsay M. Morton, Todd M. Gibson, Karen Pawlish, Dennis D. Weisenburger, Charles F. Lynch, Marc T. Goodman, Eric A. Engels
Journal: American Journal of Hematology (2012)

Case reports of Burkitt lymphoma ( BL ) in transplant recipients suggest that the risk is markedly elevated. Therefore, we investigated the incidence of BL in 203,557 solid organ recipients in the U.S. Transplant Cancer Match Study (1987–2009) and compared it with the general population using standardized incidence ratios. We also assessed associations with demographic and clinical characteristics, and treatments used to induce therapeutic immunosuppression. BL incidence was 10.8 per 100,000 person‐years, representing 23‐fold (95% confidence interval ( CI ) 19–28) greater risk than in the general population, and it peaked 3–8 years after the time of transplantation. In adjusted analyses, BL incidence was higher in recipients transplanted when &lt;18 vs. ≥35 years (incidence rate ratio [IRR] 3.49, 95% CI 2.08–5.68) and in those transplanted with a liver (IRR 2.91, 95% CI 1.68–5.09) or heart ( IRR 2.39, 95% CI 1.30–4.31) compared with kidney. BL incidence was lower in females than males ( IRR 0.45, 95% CI 0.28–0.71), in blacks than whites ( IRR 0.33, 95% CI 0.12–0.74), in those with a baseline Epstein‐Barr virus ( EBV )‐seropositive versus EBV ‐seronegative status ( IRR 0.34, 95% CI 0.13–0.93), and in those treated with azathioprine ( IRR 0.56, 95% CI 0.34–0.89) or corticosteroids ( IRR 0.48, 95% CI 0.29–0.82). Tumors were EBV ‐positive in 69% of 32 cases with results. EBV positivity was 90% in those aged &lt;18 years and 59% in those aged 18+ years. In conclusion, BL risk is markedly elevated in transplant recipients, and it is associated with certain demographic and clinical features. EBV was positive in most but not all BL cases with results. Am. J. Hematol. 88:245–250, 2013. © 2012 Wiley Periodicals, Inc.
The &lt;italic&gt;In Vitro&lt;/italic&gt; and &lt;italic&gt;In Vivo&lt;/italic&gt; Analysis of Mammalian Tumor Viruses. IV. Antibody Response and Tumor Induction with Polyoma Virus in Different Species&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Marian Fogel, Leo Sachs
Journal: JNCI Journal of the National Cancer Institute (1960)

With hemagglutination inhibition as a test for the presence of antibodies, the antibody response curves, in relation to tumor induction, have been studied after inoculation of polyoma virus into newborn or 2-day-old animals. The study included: species susceptible to tumor induction with polyoma virus—hamsters, rats, and rabbits (mice had been studied previously); and species in which tumors have so far not been found—chickens, guinea pigs, and dogs. Of all the species studied, tumor-bearing mice had the highest antibody titers. The titers in tumor-bearing hamsters were always lower than in tumor-bearing mice. In rats the highest titers were obtained after intracerebral inoculation. This route of inoculation induced osteochondrosarcomas in the skull and kidney sarcomas in 100 percent of the animals. Subcutaneous inoculation in rats induced kidney sarcomas in 36 percent of the animals, and generally lower antibody titers in animals with a tumor. In rabbits, antibody titers decreased when the tumors (fibromas) regressed. Of the three species in which tumors were not observed, chickens gave the highest and guinea pigs the lowest antibody titers. The data show a species difference both for tumor induction and for antibody response.
Rapid Anthrax Test Approved
Authors: Joan Stephenson
Journal: JAMA (2004)

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
Tumor promoter benzoyl peroxide induces direct oxidative activation of protein kinase Cϵ and increases phosphorylation of STAT3
Authors: Rayudu Gopalakrishna, Jason Schiffman, Brandon Roth, Simcha Gottlieb, Usha Gundimeda
Journal: Cancer Research (2008)

3135   Benzoyl peroxide (BPO), a free radical-generating compound widely used in industry, is a tumor promoter and progression agent in mouse skin. Although it elicits many cellular effects similar to phorbol esters, the mechanism by which BPO induces tumor promotion is not known. Previously we showed that BPO induces redox-sensitive modification of protein kinase C (PKC) and that the reversibility of this modification is related to cellular resistance to peroxide induced cytotoxicity. In this study, we observed an oxidative activation of PKCϵ in BPO-treated JB6 (41 P + ) promotable cells. This activation occurred due to direct oxidative modification of the regulatory domain of PKCϵ and was reversible by various thiol antioxidants. BPO induced this activation only for a short duration in the nonpromotable JB6 (30 P - ) cell line. BPO also induced an activation of extracellular signal-regulated kinases (ERKs) 1 and 2 in JB6 P +  cells. The activation of ERKs was blocked by pretreating cells with high (2 μM) concentration of bisindolylmaleimide and by knockout of PKCϵ by using siRNA. During the period of activation of PKCϵ and ERKs, there was an increase in Ser727 phosphorylation of signal transducer and activator of transcription 3 (STAT3). This STAT3 phophorylation was substantially blocked by siRNA-mediated knockdown of PKCϵ, and partially blocked by PD98059, an ERK pathway inhibitor, and H89, a potential inhibitor of mitogen- stress-activated protein kinase 1 (MSK1). This suggests that PKCϵ plays an important role in STAT3 (Ser727) phosphorylation either directly or indirectly via the ERK-MSK1 pathway. However, in JB6 cells overexpressing PKCϵ, inhibitors that block the ERK-MSK1 pathway inhibited STAT3 (Ser727) phosphorylation only to a minimal degree, while PKCϵ siRNA-mediated knockdown maximally inhibited this phosphorylation. This suggests that while the ERK-MSK1 pathway is important in mediating upstream signals to STAT3 (Ser727) phosphorylation, in cells overexpressing PKCϵ, this isoenzyme can directly contribute to this phosphorylation. In BPO-treated JB6 cells, there was also an increase in Tyr705 phosphorylation of STAT3 suggesting activation of additional pathways in response to BPO. Conceivably, this data suggest that the oncogenic PKCϵ plays an important role in STAT3 activation that is intimately involved in cell proliferation and tumor promotion.
A Review of: “Jerome P. Kassirer. 2004.<i>On the Take: How Medicine's Complicity with Big Business Can Endanger Your Health</i>”
Authors: Alexander C. Tsai
Journal: The American Journal of Bioethics (2005)

A few months ago, while I was completing a month-long family medicine rotation with the U.S. Indian Health Service, the conversation between me and my preceptor turned to road trips, mountains, and...
On Leopards, Cheetahs, and the Cutaneous Stigmata of Onchocerciasis
Authors: Evan Rieder
Journal: JAMA Dermatology (2015)

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 Dermatology 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 Dermatology journal
US faces ethical issues after gene therapy death
Authors: Janice Hopkins Tanne
Journal: BMJ (2000)

Gene therapy is no different from other kinds of risky medical research, said Dr Arthur Caplan, professor and director of the Center for Bioethics at the University of Pennsylvania in Philadelphia, speaking at the New York Academy of Sciences earlier this week. Better regulation of all research is needed.

A gene therapy experiment at the University of Pennsylvania led to the death of Jesse Gelsinger, an 18 year old man with an inherited metabolic disorder. Dr Caplan, a well known ethicist and author, was not involved in the experiment.

Ethical issues about genetics have been …
Abstract 3592: Macrophages confer resistance to cisplatin in MTLn3 and MDA-MB 231 breast cancer cells
Authors: Joshua K. Sabari, Ramon Cabrera, Jeffrey Segall
Journal: Cancer Research (2014)

Abstract Drug resistance presents a clinical challenge to the treatment of breast cancer. Stromal cells such as macrophages may play a role in drug resistance. The purpose of this study is to examine the interaction between breast cancer cells and macrophages and its effects on drug therapy resistance. The five-year survival for localized hormone sensitive disease is 98% and as low as 15% for triple negative (ER/PR/Her2) and metastatic disease. Most targeted anticancer therapies, as well as cytotoxic therapies, are burdened by the development of cancer cell resistance. It is hypothesized that the tumor microenvironment may confer innate resistance to drug therapy. It is well established that chemotactic factors found in the tumor microenvironment can promote motility and invasion. We hypothesize that tumor associated macrophages can confer drug resistance to breast cancer cells via overexpression of epidermal growth factor (EGF). EGF is overexpressed in many tumor types and is clinically correlated with a poor overall prognosis. Previous studies have shown that EGF is produced by non-tumor cells in the microenvironment; in particular tumor-associated macrophages (TAM) and endothelial cells. We have previously shown that macrophages and tumor cells, via a paracrine loop, are necessary and sufficient for comigration and invasion. Breast cancer cells produce colony stimulating factor 1 (CSF-1) which positively feeds back to increase macrophage expression of EGF. Increased EGF expression in turn leads to tumor growth and invasion. We selected two triple negative breast cancer cell lines, MDA-MB 231 (human mammary adenocarcinoma) and MTLn3 (rat mammary adenocarcinoma) that were transfected to express GFP. Co-culture cell survival assays were performed with macrophages, fibroblasts, and endothelial cells. All tissue culture was completed in DMEM (HyClone) plus 10% FBS. Cells were grown for 24 hours in co-culture, treated with chemotherapy (doxorubicin or cisplatin at a range of concentrations) for 24 hours, and then analyzed at 72 hours using the DXP-10 Calibur analyzer. Prior to analysis, cells were again replated to measure “replating efficiency” i.e. chemoresistant cell survival. We found that coculture with macrophages increased tumor cell survival upon exposure to cisplatin. We conclude that macrophages are an important component of the tumor microenvironment that may play a role in chemotherapy resistance. Citation Format: Joshua K. Sabari, Ramon Cabrera, Jeffrey Segall. Macrophages confer resistance to cisplatin in MTLn3 and MDA-MB 231 breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3592. doi:10.1158/1538-7445.AM2014-3592
Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2014 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline
Authors: John R. Downs, Patrick G. O'Malley
Journal: Annals of Internal Medicine (2015)

In December 2014, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the management of dyslipidemia for cardiovascular disease risk reduction in adults. This synopsis summarizes the major recommendations.On 30 September 2013, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, developed a simple 1-page algorithm, and rated each of 26 recommendations by using the Grading of Recommendations Assessment, Development, and Evaluation system.This synopsis summarizes key features of the guideline in 5 areas: elimination of treatment targets, additional tests for risk prediction, primary and secondary prevention, and laboratory testing.
Abstract 20099: Adiponectin Inhibits Maladaptive Cardiac Remodeling in Cardiac Disease by Increasing Matrix Metalloproteinase-9 Activity
Authors: Alexander C Jenke, Robert Schur, Luise Holzhauser, Wolfgang Poller, Heinz-Peter Schultheiss, Carsten Skurk
Journal: Circulation (2014)

Introduction: Adiponectin (APN) is an immunomodulatory adipocytokine that inhibits left ventricular hypertrophy induced by pressure overload as well as hypertension. Here, we investigated whether APN inhibits adverse extracellular matrix (ECM) remodeling in in experimental models of myocardial infarction (MI) and coxsackievirus B3 (CVB3) myocarditis by affecting matrix metalloproteinase (MMP) expression and its possible mechanisms. Methods: Experimental CVB3 myocarditis and experimental MI were induced in APN-KO and wild-type (WT) C57/BL6J mice. RNA and protein expression/enzymatic activity of MMPs was quantified by qRT-PCR and zymography, respectively. Activation status of protein kinases was determined by immunoblot. Results: In cultured cardiac myocytes and fibroblasts APN induced MMP-9 gene and protein expression by activation of AMPK and MEK1 without affecting MMP-2, MMP-3 and MMP-13. Inhibition with PD098059 and Compound C almost completely abolished MMP-9 up-regulation in this setting. AMPK as well...
Alternatively spliced isoforms of WT1 control podocyte-specific gene expression
Authors: Jonathan Lefebvre, Michael Clarkson, Filippo Massa, Stephen T. Bradford, Aurelie Charlet, Fabian Buske, Sandra Lacas-Gervais, Herbert Schulz, Charlotte Gimpel, Yutaka Hata, Franz Schaefer, Andreas Schedl
Journal: Kidney International (2015)

The Wilms' tumor suppressor WT1 is a key regulator of podocyte function that is mutated in Denys-Drash and Frasier syndromes. Here we have used an integrative approach employing ChIP, exon array, and genetic analyses in mice to address general and isoform-specific functions of WT1 in podocyte differentiation. Analysis of ChIP-Seq data showed that almost half of the podocyte-specific genes are direct targets of WT1. Bioinformatic analysis further identified coactivator FOXC1-binding sites in proximity to WT1-bound regions, thus supporting coordinated action of these transcription factors in regulating podocyte-specific genes. Transcriptional profiling of mice lacking the WT1 alternative splice isoform (+KTS) had a more restrictive set of genes whose expression depends on these alternatively spliced isoforms. One of these genes encodes the membrane-associated guanylate kinase MAGI2, a protein that localizes to the base of the slit diaphragm. Using functional analysis in mice, we further show that MAGI2α is essential for proper localization of nephrin and the assembly of the slit diaphragm complex. Finally, a dramatic reduction of MAGI2 was found in an LPS mouse model of glomerular injury and in genetic cases of human disease. Thus, our study highlights the central role of WT1 in podocyte differentiation, identifies that WT1 has a central role in podocyte differentiation, and identifies MAGI2α as the crucial isoform in slit diaphragm assembly, suggesting a causative role of this gene in the etiology of glomerular disorders.
US lawmakers pass bill on violence to fetus
Authors: Fred Charatan
Journal: BMJ (2001)

The US House of Representatives last month passed a bill, by a vote of 252 to 172, that, if approved by the Senate, would give a new legal status to the fetus. It establishes criminal penalties for harming a fetus during the commission of a federal offence against a pregnant woman.

Republican Representative Lindsey Graham of South Carolina, who introduced the Unborn Victims of Violence Act, wrote: “Under the bill, criminals who commit …
Lower mortality with direct right atrial neuronal nitric oxide synthase gene transfer in first three days post myocardial infarction
Authors: Tom A Dawson, Dan Li, Timothy Woodward, Zoe E Barber, Lijun Wang, David J Paterson
Journal: Circulation (2007)

Sudden cardiac death (SCD) post myocardial infarction (MI) is associated with increased sympathetic and decreased vagal activity. This may be related to oxidative stress disrupting the bioavailabil...
Rapid selection of complement-inhibiting protein variants in group A Streptococcus epidemic waves
Authors: Nancy P. Hoe, Kazumitsu Nakashima, Slawomir Lukomski, Diana S Grigsby, Mengyao Liu, Parichher Kordari, Shu Jun Dou, Xi Pan, Jaana Vuopio-Varkila, Saara Salmelinna, Allison McGeer, Donald E. Low, Benjamin Schwartz, Anne Schuchat, Steven Naidich, Dsvid De Lorenzo, Yun Xin Fu, James M. Musser
Journal: Nature Medicine (1999)
1049. Engineered ZFPs Can Prevent Limb Loss in Mice
Authors: Jun Yu, Reed Hickey, Yan Huang, Edward Rebar, William C. Sessa, Frank J. Giordano
Journal: Molecular Therapy (2004)

Top of pageAbstract
The ability to engineer artificial zinc finger protein (ZFP)-based transcription factors has led to a new and growing area of gene therapy, targeted regulation of endogenous genes. One potential advantage of this approach is that it facilitates expression of all natural splice variants of a targeted gene. To investigate the therapeutic implications of this approach we used an engineered ZFP (VOP32E) that activates transcription of the VEGF-A gene. An adenovirus encoding VOP32E was constructed and used to evaluate the ability of VOP32E-based VEGF-A expression to rescue hindlimb ischemia (HI) in aged C57BL/6J (WT) mice. HI was created by excision of left common femoral artery and proximal portion of saphenous artery. In aged WT mice this intervention results in a high incidence of limb loss. In addition, unlike young WT mice, blood flow does not return to normal in these mice by means of the endogenous response to ischemia. Delivery of Ad-VOP32E to the adductor muscles of these mice resulted in a significant improvement in a clinical score and reduced the incidence of limb loss as compared to mice treated with a control virus (Ad-RFP). This was accompanied by a significant increase in blood flow as measured serially (1,2 and 4 weeks) after treatment with a modified laser doppler system that measures deep tissue blood flow. Immunohistochemical staining for PECAM demonstrated an increase in capillary density in the ZFP treated limbs, and quantitative RT-PCR demonstrated an increase in total VEGF mRNA, as well as increased expression of all major splice variants. This data documents that engineered transcription factors can be effective therapeutically in mammalian systems, and specifically that endogenous VEGF-A activation by an engineered ZFP is effective in an ischemia model that does not have spontaneous recovery.
Abstract B97: A phase II trial of low-dose multiagent chemotherapy with gemcitabine, taxotere, xeloda, and cisplatin (GTX-C) in subjects with metastatic pancreatic cancer
Authors: Dung Le, Daniel Laheru, Luis A. Diaz
Journal: Cancer Research (2015)

Abstract Background: Triplet chemotherapy has been shown to delay the emergence of resistance and extend survival in patients with metastatic pancreatic adenocarcinoma. Four drug regimens, even at low doses, may further improve survival by simultaneously targeting multiple oncogenic pathways. Methods: A phase II study of GTX-C (capecitabine 500 mg bid on days 1-14, and the combination of gemcitabine 500 mg/m2 (10 mg/m2/min), taxotere 20 mg/m2 and cisplatin 20 mg/m2 on days 4 and 11) was initiated in newly diagnosed untreated metastatic pancreatic cancer patients. The primary endpoint was progression-free survival rate at 6 months and designed such that the regimen would be considered active if the 6-month PFS rate was &amp;gt;75% and inactive if &amp;lt; 50%. Results: Twenty-eight patients were enrolled. All patients were ECOG 0-1. Eighty-six percent of patients had evidence of liver metastases and 25% had biliary stents in place at time of study initiation. Median CA19-9 was 6,159 U/mL (37-154,323 U/mL). Median length of follow-up was 10.1 months. Grade 3/4 related adverse events included: nausea/vomiting (7%), transaminitis (10%), anemia (14%), thrombocytopenia (24%), and neutropenia (55%). However, febrile neutropenia occurred in only 3 patients (10%) and not until cycles 6, 14, and 15. PFS rate at 6 months was 74.2% (95% CI: 53.3% - 86.8%). The partial response (PR) rate was 50%, stable disease (SD) rate was 39% and the disease control rate (DCR) was 89%. CA19-9 declines of &amp;gt;80% occurred in 77% of patients with measurable levels. Estimated median PFS was 8.4 months (95% CI: 6.1-10.6 months) and OS was 12.9 months (95% CI: 10.0-NA months) as of 11/14/2013. Ten additional patients have been enrolled onto an expansion cohort in which the period off between cycles has been changed from 7 to 14 days. Conclusions: GTX-C is highly active and well-tolerated in patients with metastatic pancreatic cancer and should be tested in a larger, comparative study. Clinical trial information: NCT01459614. Citation Format: Dung Le, Daniel Laheru, Luis A. Diaz, Jr. A phase II trial of low-dose multiagent chemotherapy with gemcitabine, taxotere, xeloda, and cisplatin (GTX-C) in subjects with metastatic pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B97.