tbuckley/cabot-search huggingface dataset:
Effectiveness of Over-the-Counter Nicotine Replacement Therapy
Authors: David O. Antonuccio
Journal: JAMA (2002)

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
An alternative approach to medical genetics based on modern evolutionary biology. Part 1: mutation and symbiogenesis
Authors: Frank P Ryan
Journal: Journal of the Royal Society of Medicine (2009)

The need to understand the genetic underpinning of common diseases, such as cancer, diabetes and autoimmune disorders, is a major challenge facing medical genetics. While many disorders involve a complex interaction between genetic traits and environmental influences, a significant proportion involve specific genetic causes that are diagnosable and thus amenable to therapeutic approaches, including family counselling, specific lines of chemically-directed therapy and even the possibility of addressing the underlying genetic causation through specific genetic therapy. The genetic approach to medicine has always found commonalities with the disciplines of evolutionary biology: only when we understand the evolutionary origins of the human genome can we aspire to understand how ‘normality’, in terms of genetics and epigenetics, becomes subverted in disease. Since the 1930s, mutation has been assumed to be the exclusive explanation of the hereditary basis of disease. But advances in evolutionary biology over the last two decades have introduced three additional, and important, sources of hereditary variation, namely symbiogenesis, particularly symbiogenesis involving viruses, epigenetics and hybridogenesis, all of which are now seen to have played important roles in the evolution of biodiversity. These additional mechanisms have played a major role in the evolution of the human genome – indeed they help to explain what would otherwise appear to be some paradoxical aspects of its construction and make-up. In this paper, and the four linked papers that follow it, I shall explain the evolutionary advances and show how, together with the knowledge already accrued from the study of mutation, they provide a more comprehensive understanding of the hereditary basis of human disease.
Multicenter Phase II Trial of Neoadjuvant Pemetrexed Plus Cisplatin Followed by Extrapleural Pneumonectomy and Radiation for Malignant Pleural Mesothelioma
Authors: Lee M. Krug, Harvey I. Pass, Valerie W. Rusch, Hedy L. Kindler, David J. Sugarbaker, Kenneth E. Rosenzweig, Raja Flores, Joseph S. Friedberg, Katherine Pisters, Matthew Monberg, Coleman K. Obasaju, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2009)

Purpose Neoadjuvant pemetrexed plus cisplatin was administered, followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation (RT), to assess the feasibility and efficacy of trimodality therapy in stage I to III malignant pleural mesothelioma. Patients and Methods Requirements included stage T1-3 N0-2 disease, no prior surgical resection, adequate organ function (including predicted postoperative forced expiratory volume in 1 second ≥ 35%), and performance status 0 to 1. Patients received pemetrexed 500 mg/m 2 plus cisplatin 75 mg/m 2 for four cycles. Patients without disease progression underwent EPP followed by RT (54 Gy). The primary end point was pathologic complete response (pCR) rate. Results Seventy-seven patients received chemotherapy. All four cycles were administered to 83% of patients. The radiologic response rate was 32.5% (95% CI, 22.2 to 44.1). Fifty-seven patients proceeded to EPP, which was completed in 54 patients. Three pCRs were observed (5% of EPP). Forty of 44 patients completed irradiation. Median survival in the overall population was 16.8 months (95% CI, 13.6 to 23.2 months; censorship, 33.8%). Patients completing all therapy had a median survival of 29.1 months and a 2-year survival rate of 61.2%. Radiologic response of complete or partial response was associated with a median survival of 26.0 months compared with 13.9 months for patients with stable disease or progressive disease (P = .05). Conclusion This multicenter trial showed that trimodality therapy with neoadjuvant pemetrexed plus cisplatin is feasible with a reasonable long-term survival rate, particularly for patients who completed all therapy. Radiologic response to chemotherapy, but not sex, histology, disease stage, or nodal status, was associated with improved survival.
THE VIBRISSA DERMAL PAPILLA AND ITS INFLUENCE ON EPIDERMAL TISSUES*
Authors: R. F. OLIVER
Journal: British Journal of Dermatology (1969)

Journal Article THE VIBRISSA DERMAL PAPILLA AND ITS INFLUENCE ON EPIDERMAL TISSUES Get access R. F. OLIVER R. F. OLIVER Medical Research Council, Unit for Research on the Experimental Pathology of the, Skin, Medical School, University, Birmingham 15 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue s3, 1 June 1969, Pages 55–65, https://doi.org/10.1111/j.1365-2133.1969.tb12855.x Published: 01 June 1969
Point-of-care ultrasonography in patients admitted with respiratory symptoms: a single-blind, randomised controlled trial
Authors: Christian B Laursen, Erik Sloth, Annmarie Touborg Lassen, René dePont Christensen, Jess Lambrechtsen, Poul Henning Madsen, Daniel Pilsgaard Henriksen, Jesper Rømhild Davidsen, Finn Rasmussen
Journal: The Lancet Respiratory Medicine (2014)
Rituximab, Fludarabine, Cyclophosphamide, and Mitoxantrone: A New, Highly Active Chemoimmunotherapy Regimen for Chronic Lymphocytic Leukemia
Authors: Francesc Bosch, Pau Abrisqueta, Neus Villamor, María José Terol, Eva González-Barca, Christelle Ferra, Marcos González Diaz, Eugenia Abella, Julio Delgado, Félix Carbonell, José Antonio García Marco, Lourdes Escoda, Secundino Ferrer, Encarnación Monzó, Yolanda González, Cristina Estany, Isidro Jarque, Olga Salamero, Ana Muntañola, Emili Montserrat
Journal: Journal of Clinical Oncology (2009)

The addition of monoclonal antibodies to chemotherapy has significantly improved treatment of chronic lymphocytic leukemia (CLL). Based on excellent results with the chemotherapy-only regimen fludarabine, cyclophosphamide, and mitoxantrone (FCM), we built a new chemoimmunotherapy combination--rituximab plus FCM (R-FCM). We report a phase II clinical trial consisting of an initial treatment with R-FCM followed by rituximab maintenance.Seventy-two untreated CLL patients age 70 years or younger received rituximab 500 mg/m(2) on day 1 (375 mg/m(2) the first cycle), fludarabine 25 mg/m(2) IV on days 1 to 3, cyclophosphamide 200 mg/m(2) on days 1 to 3, and mitoxantrone 6 mg/m(2) IV on day 1, given at 4-week intervals with up to six cycles supported with colony-stimulating factor. Patients achieving response received maintenance with rituximab 375 mg/m(2) every 3 months for 2 years.The overall response, minimal residual disease (MRD) -negative complete response (CR), MRD-positive CR, and partial response rates were 93%, 46%, 36%, and 11%, respectively. Severe neutropenia developed in 13% of patients. Major and minor infections were reported in 8% and 5% of cycles, respectively. Advanced clinical stage, del(17p), or increased serum beta2-microglobulin levels correlated with a lower CR rate.R-FCM is highly effective in previously untreated CLL, with an 82% CR rate and a high proportion of MRD-negative CRs (46%). Treatment toxicity is acceptable. Parameters correlating with a lower response rate were advanced clinical stage, high serum beta2-microglobulin levels, and del(17p). Based on these results, R-FCM warrants further investigation in randomized clinical trials.
Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential
Authors: Masood A Shammas, Hemanta Koley, Ramesh B Batchu, Robert C Bertheau, Alexei Protopopov, Nikhil C Munshi, Raj K Goyal
Journal: Molecular Cancer (2005)

In cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells.We designed siRNAs against two different regions of telomerase gene and evaluated their effect on telomere length, proliferative potential, and gene expression in Barrett's adenocarcinoma SEG-1 cells. The mixture of siRNAs in nanomolar concentrations caused a loss of telomerase activity that appeared as early as day 1 and was essentially complete at day 3. Inhibition of telomerase activity was associated with marked reduction in median telomere length and complete loss of detectable telomeres in more than 50% of the treated cells. Telomere loss caused senescence in 40% and apoptosis in 86% of the treated cells. These responses appeared to be associated with activation of DNA sensor HR23B and subsequent activation of p53 homolog p73 and p63 and E2F1. Changes in these gene regulators were probably the source of observed up-regulation of cell cycle inhibitors, p16 and GADD45. Elevated transcript levels of FasL, Fas and caspase 8 that activate death receptors and CARD 9 that interacts with Bcl10 and NFKB to enhance mitochondrial translocation and activation of caspase 9 were also observed.These studies show that telomerase siRNAs can cause effective suppression of telomerase and telomere shortening leading to both cell cycle arrest and apoptosis via mechanisms that include up-regulation of several genes involved in cell cycle arrest and apoptosis. Telomerase siRNAs may therefore be strong candidates for highly selective therapy for chemoprevention and treatment of Barrett's adenocarcinoma.
Coercive US Interrogation Policies
Authors: Leonard Rubenstein, Christian Pross, Frank Davidoff, Vincent Iacopino
Journal: JAMA (2005)

AS WORLD ATTENTION HAS FOCUSED ON ALLEGAtions of torture and ill treatment (cruel, inhuman, and degrading treatment or punishment) by US forces, there have been questions about the role of physicians and other health professionals in abusive interrogations. Considerable light has been shed on these allegations by documents released in 2004 and 2005 under the Freedom of Information Act and official US Department of Defense (DoD) investigations initiated since the Abu Ghraib investigations in 2004, including an internal review of medical practices regarding detainees by the US Army surgeon general. Following the release of these documents and reports, in June 2005, the assistant secretary of defense for health affairs released new ethical guidelines for all health care personnel, including physicians, nurses, and medics. The new guidelines are troubling, however, because they do not come to terms with the participation of physicians and other health care professionals in officially authorized interrogation practices that are absolutely prohibited by international human rights law, the Third Geneva Convention, and US military and domestic law that criminalizes torture, including psychological torture. While the new DoD ethical guidelines apply to all health care personnel, we focus on how the guidelines enable physicians to facilitate and monitor abusive interrogation practices and subvert well-established ethical duties to support health and human dignity.
Elevating High-Density Lipoprotein Cholesterol in Apolipoprotein E-Deficient Mice Remodels Advanced Atherosclerotic Lesions by Decreasing Macrophage and Increasing Smooth Muscle Cell Content
Authors: James X. Rong, Jie Li, Ernane D. Reis, Robin P. Choudhury, Hayes M. Dansky, Valerie I. Elmalem, John T. Fallon, Jan L. Breslow, Edward A. Fisher
Journal: Circulation (2001)

Background HDL cholesterol levels are inversely correlated with coronary heart disease risk in humans, and in animal studies, HDL elevation decreases formation and progression of foam-cell lesions. The potential for HDL to affect preexisting advanced atherosclerotic lesions is not known. To approach this issue, we used a novel mouse aortic transplantation model. Methods and Results ApoE-deficient (EKO) mice were fed a Western-type diet for 6 months, and thoracic aortic segments containing advanced lesions replaced segments of the abdominal aorta of 4-month-old EKO syngeneic mice not expressing (plasma HDL cholesterol ≈26 mg/dL) or expressing (HDL ≈64 mg/dL) a human apoAI (hAI) transgene. Both types of recipients had comparable non-HDL cholesterol levels. Five months after transplantation, mice were killed and grafts analyzed. Compared with lesion area in pretransplant mice (0.14±0.04 mm 2 , mean±SEM), there was progression in the EKO recipients (0.39±0.06 mm 2 , P &lt;0.01). Compared with EKO recipients, hAI/EKO recipients had retarded progression (0.24±0.04 mm 2 , P &lt;0.05). Immunostaining for CD68 and other macrophage-associated proteins, monocyte chemoattractant protein-1, acyl coenzyme A:cholesterol acyltransferase, and tissue factor, in lesions of pretransplant and EKO recipient mice showed abundant macrophages. In contrast, compared with any other group, lesional macrophage area in hAI/EKO mice decreased &gt;80% ( P &lt;0.003), and smooth muscle cell content (α-actin staining) increased &gt;300% ( P &lt;0.006). The decrease in macrophages and increase in smooth muscle cells was primarily in the superficial subendothelial layer. Conclusions Increasing HDL cholesterol levels in EKO mice retards progression of advanced atherosclerotic lesions and remodels them to a more stable-appearing phenotype.
Activation of Sterile20-Like Kinase 1 in Proteasome Inhibitor Bortezomib–Induced Apoptosis in Oncogenic K-ras-Transformed Cells
Authors: Fuminori Teraishi, Wei Guo, Lidong Zhang, Fengqing Dong, John J. Davis, Takehiko Sasazuki, Senji Shirasawa, Jinsong Liu, Bingliang Fang
Journal: Cancer Research (2006)

Abstract Bortezomib (PS-341), a specific proteasome inhibitor, exhibits antitumor activity against a wide range of malignancies. However, the molecular mechanisms by which bortezomib causes apoptosis selectively in cancer cells still remain unclear. Ras signaling is involved in multiple cellular processes, including cell cycle progression, differentiation, and apoptosis, and can either promote or inhibit apoptosis depending on the type of apoptotic stimuli and the cell model. Here, we investigated the role of K-ras signaling in bortezomib-induced apoptosis. We found that K-ras-transformed cells were more susceptible to bortezomib-induced apoptosis than were nontransformed cells and that bortezomib-induced apoptosis was mainly caspase dependent in K-ras-transformed cells. We also found that mammalian sterile20-like kinase 1 (MST1) was activated by bortezomib in K-ras-transformed cells and K-ras-mutated cancer cells. Treatment of K-ras-transformed cells with bortezomib resulted in translocation of MST1 from cytoplasm into the nucleus and an increase of phosphorylated histone H2B and histone H2AX. Moreover, pretreatment with leptomycin B, an inhibitor of the nuclear export signal receptor, dramatically enhanced bortezomib-mediated MST1 activation, phosphorylation of histones H2B and H2AX, and apoptosis induction in K-ras-transformed cells. Knockdown of MST1 expression by small interfering RNA diminished bortezomib-induced apoptosis or caspase-3 activation. Our data suggested that bortezomib may be useful for treatment of K-ras-mutated cancer cells, and MST1 is one of the mediators for bortezomib-induced apoptosis in K-ras-transformed cells. (Cancer Res 2006; 66(12): 6072-9)
RABBIT PLATELET BACTERICIDAL PROTEIN
Authors: Babette B. Weksler, R. L. Nachman
Journal: The Journal of Experimental Medicine (1971)

The heat-stable antibacterial activity of rabbit serum against Gram-positive microorganisms has been shown to reside in a cationic protein fraction of platelet lysosomal granules. The activity is released during platelet aggregation. No plasma or serum component is required for the bactericidal effect. The platelet bactericidin resembles the antibacterial proteins of leukocyte granules both in cellular localization and in biochemical characteristics. It can be differentiated from platelet factor 4, the antiheparin factor, which is also a basic protein in platelet granules. The antibacterial effect of the platelet bactericidin may be related to the metabolic activity of the organisms. This antibacterial activity of platelets may represent another means by which platelets can participate in host inflammatory defense reactions.
Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation
Authors: Manesh R. Patel, Kenneth W. Mahaffey, Jyotsna Garg, Guohua Pan, Daniel E. Singer, Werner Hacke, Günter Breithardt, Jonathan L. Halperin, Graeme J. Hankey, Jonathan P. Piccini, Richard C. Becker, Christopher C. Nessel, John F. Paolini, Scott D. Berkowitz, Keith A.A. Fox, Robert M. Califf
Journal: New England Journal of Medicine (2011)

The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin.
Western diet induces dysbiosis with increased<i>E coli</i>in CEABAC10 mice<i>,</i>alters host barrier function favouring AIEC colonisation
Authors: Margarita Martinez-Medina, Jérémy Denizot, Nicolas Dreux, Frédéric Robin, Elisabeth Billard, Richard Bonnet, Arlette Darfeuille-Michaud, Nicolas Barnich
Journal: Gut (2013)

<h3>Objective</h3> Western diet is a risk factor for Crohn9s disease (CD). Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is abnormally expressed in CD patients. This allows adherent-invasive <i>Escherichia coli</i> (AIEC) to colonise the gut mucosa and leads to inflammation. We assessed the effects of a high fat/high sugar (HF/HS) Western diet on gut microbiota composition, barrier integrity and susceptibility to infection in transgenic CEABAC10 mice expressing human CEACAMs. <h3>Design</h3> Colonic microbiota composition and susceptibility of CEABAC10 mice to AIEC LF82 bacteria infection were determined in mice fed a conventional or HF/HS diet. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein and mucin expression and localisation, and by determining histological score and levels of cytokine release. <h3>Results</h3> HF/HS diet led to dysbiosis in WT and transgenic CEABAC10 mice, with a particular increase in <i>E coli</i> population in HF/HS-fed CEABAC10 mice. These mice showed decreased mucus layer thickness, increased intestinal permeability, induction of <i>Nod2</i> and <i>Tlr5</i> gene transcription, and increased TNFα secretion. These modifications led to a higher ability of AIEC bacteria to colonise the gut mucosa and to induce inflammation. <h3>Conclusions</h3> Western diet induces changes in gut microbiota composition, alters host homeostasis and promotes AIEC gut colonisation in genetically susceptible mice. These results support the multifactorial aetiology of CD and highlight the importance of diet in CD pathogenesis.
Predicting outcomes and complications of percutaneous endoscopic gastrostomy
Authors: F. Figueiredo, M. da Costa, A. Pelosi, R. Martins, L. Machado, E. Francioni
Journal: Endoscopy (2007)

See also: Commentaire de travail de F. A. F. FigueiredoR et al., pp. 333Endoscopy 2007; 39(04): 383-383DOI: 10.1055/s-0032-1306925
Major Histocompatibility Complex–independent Recognition of a Distinctive Pollen Antigen, Most Likely a Carbohydrate, by Human CD8+ α/β T Cells
Authors: Silvia Corinti, Raffaele De Palma, Angelo Fontana, Maria Cristina Gagliardi, Carlo Pini, Federica Sallusto
Journal: The Journal of Experimental Medicine (1997)

We have isolated CD8+ alpha/beta T cells from the blood of atopic and healthy individuals which recognize a nonpeptide antigen present in an allergenic extract from Parietaria judaica pollen. This antigen appears to be a carbohydrate because it is resistant to proteinase K and alkaline digestion, is hydrophilic, and is sensitive to trifluoromethane-sulphonic and periodic acids. In addition, on a reverse-phase high performance liquid chromatography column the antigen recognized by CD8(+) T cells separates in a fraction which contains >80% hexoses (glucose and galactose) and undetectable amounts of proteins. Presentation of this putative carbohydrate antigen (PjCHOAg) to CD8+ T cell clones is dependent on live antigen presenting cells (APCs) pulsed for >1 h at 37 degrees C, suggesting that the antigen has to be internalized and possibly processed. Indeed, fixed APCs or APCs pulsed at 15 degrees C were both unable to induce T cell response. Remarkably, PjCHOAg presentation is independent of the expression of classical major histocompatibility complex (MHC) molecules or CD1. CD8+ T cells stimulated by PjCHOAg-pulsed APCs undergo a sustained [Ca2+]i increase and downregulate their T cell antigen receptors (TCRs) in an antigen dose- and time-dependent fashion, similar to T cells stimulated by conventional ligands. Analysis of TCR Vbeta transcripts shows that six independent PjCHOAg-specific T cell clones carry the Vbeta8 segment with a conserved motif in the CDR3 region, indicating a structural requirement for recognition of this antigen. Finally, after activation, the CD8+ clones from the atopic patient express CD40L and produce high levels of interleukins 4 and 5, suggesting that the clones may have undergone a Th2-like polarization in vivo. These results reveal a new class of antigens which triggers T cells in an MHC-independent way, and these antigens appear to be carbohydrates. We suggest that this type of antigen may play a role in the immune response in vivo.