tbuckley/cabot-search huggingface dataset:
Ceramide analogue 14S24 selectively recovers perturbed human skin barrier
Authors: K. Vávrová, A. Hrabálek, S. Mac-Mary, P. Humbert, P. Muret
Journal: British Journal of Dermatology (2007)

Topical ceramide application is an effective therapeutic approach in skin disorders with disturbed barrier function, including atopic dermatitis and psoriasis.To evaluate ceramide analogue N-tetracosanoyl-(l)-serine tetradecyl ester (14S24) using a novel ex vivo model.Freshly excised human skin was disrupted by lipid extraction, tape stripping and sodium lauryl sulphate (SLS) treatment. Barrier perturbation was evaluated by the measurement of transepidermal water loss (TEWL), skin hydration and the penetration of model compound, theophylline (TH), assessed by microdialysis. The effect of topical 5% 14S24 was compared with a commercial formulation containing a skin lipid mixture (LR) and control formulation with no skin lipids (L).Both LR and 14S24 produced significant recovery of TEWL and TH penetration in extracted and tape-stripped skin with 14S24 being significantly more effective. In SLS-treated skin, 14S24 decreased TEWL but not TH penetration; LR was inactive. L improved skin hydration but not barrier characteristics. Weak correlation between TEWL and TH penetration was observed in extracted and tape-stripped skin but not in SLS-treated skin.Cutaneous microdialysis can serve as a useful tool for the evaluation of skin barrier recovery by topical formulations ex vivo whereas TEWL may not be an appropriate measure of skin barrier function in such studies. The excellent barrier repair activity of 14S24 could be beneficial in skin disorders with ceramide deficiency.
Carbenicillin: Clinical and Laboratory Experience with a Parenterally Administered Penicillin for Treatment of Pseudomonas Infections
Authors: HAROLD C. NEU
Journal: Annals of Internal Medicine (1969)

Carbenicillin, an alpha carboxybenzyl penicillin, was evaluated in the treatment of pseudomonas, proteus, and enterobacter infections in 41 patients. It was possible to obtain blood and urine concentrations of carbenicillin that were bactericidal for most Pseudomonas and Proteus strains by use of constant intravenous infusions of the drug. Carbenicillin was highly effective in the treatment of urinary tract infections and bacteremia. It was less effective in pulmonary infections, particularly in patients with advanced cystic fibrosis. Klebsiella overgrowth occurred in some patients treated for pulmonary and wound infections. Transient elevations of serum glutamic-oxalacetic transaminase (SGOT) were noted in children. Treatment with 30 g/day did not cause renal, hematologic, or neurologic toxicity. Carbenicillin represents a major advance in the therapy of serious pseudomonas and indole-positive proteus infections.
SNPs in PI3K-PTEN-mTOR and Brain Metastases in NSCLC—Response
Authors: Qianxia Li, Huihua Xiong, Xianglin Yuan
Journal: Clinical Cancer Research (2014)

We thank Giovannetti and colleagues for their thoughtful comments about our recent article ([1][1]) entitled “Associations between Single-Nucleotide Polymorphisms in the PI3K-PTEN-AKT-mTOR Pathway and Increased Risk of Brain Metastasis in Patients with Non–Small Cell Lung Cancer.” In their
Abstract 4746: Type I NKT cells mediate anti-tumor immunity through a TNF-α- and NOS-dependent pathway when stimulated with β-ManCer
Authors: Jessica J. O'Konek, Petr Illarinov, Deborah Stewart Khursigara, Elena Ambrosino, Liat Izhak, Bernard F. Castillo, Ravinder Raju, Maryam Khalili, Hee-Yong Kim, Amy Howell, Gurdyal S. Besra, Steven A. Porcelli, Jay A. Berzofsky, Masaki Terabe
Journal: Cancer Research (2011)

Abstract CD1d-restricted type I NKT cells have been shown to play a critical role in the induction of tumor immunity by producing IFN-γ, which activates effector arms such as NK cells and CD8+ T cells. It has been considered that IFN-γ is necessary for type I NKT cell-induced tumor immunity. In this study, we show that type I NKT cells can induce strong tumor immunity through an IFN-γ-independent pathway when activated with a new type of agonistic antigen, β-mannosylceramide (β-ManCer). The protection induced by β-ManCer treatment was completely abrogated in type I NKT cell deficient Jα18 KO mice. With the observations that in vitro activation of type I NKT cells by β-ManCer was blocked by anti-CD1d blocking monoclonal antibody and that β-ManCer-loaded CD1d dimers bind to type I NKT cells and stimulate type I NKT cell hybridomas in an APC-free system, we concluded that recognition of CD1d presented β-ManCer by a TCR of type I NKT cells is necessary for the protection. Surprisingly β-ManCer-induced protection was not abrogated in IFN-γ deficient mice, which is in contrast with the protection induced by a prototypic agonist α-galactosylceramide (α-GalCer). Instead, β-ManCer-induced protection was dependent on nitric oxide synthase (NOS) and TNF-α since blockade of either completely abrogated the protection while the blockade did not affect protection induced by α-GalCer. The conclusion that NKT cells activated with β-ManCer utilize a different pathway from that used by the cells activated with α-GalCer to enhance tumor immunity was confirmed with the observation that the combination of both antigens synergistically enhanced tumor immunity when suboptimal doses of each were used. These data demonstrate that NKT cells mediate tumor immunity through a TNF-α- and NOS-dependent pathway when stimulated with β-ManCer and that β-ManCer represents a new class of type I NKT cell agonist. Since we observed that human type I NKT cells also can be activated by β-ManCer, β-ManCer may provide a new intervention against cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4746. doi:10.1158/1538-7445.AM2011-4746
High-pressure inflations do not insure ‘adequate’ stent deployment: Evidence from intravascular ultrasound
Authors: Anthony C. De Franco, E.Murat Tuzcu, Khaled M. Ziada, Nirav Shah, Seilesh Babu, A.Michael Lincoff, Russell Raymond, Patrick L. Whitlow, Stephen G. Ellis, Steven E. Nissen
Journal: Journal of the American College of Cardiology (1996)
CD123 targeting oncolytic adenoviruses suppress acute myeloid leukemia cell proliferation in vitro and in vivo
Authors: G Li, X Li, H Wu, X Yang, Y Zhang, L Chen, X Wu, L Cui, L Wu, J Luo, X Y Liu
Journal: Blood Cancer Journal (2014)

We report here a novel strategy to redirect oncolytic adenoviruses to CD123 by carry a soluble coxsackie-adenovirus receptor (sCAR)-IL3 expression cassette in the viral genome to form Ad.IL3, which sustainably infected acute myeloid leukemia (AML) cells through CD123. Ad.IL3 was further engineered to harbor gene encoding manganese superoxide dismutase (MnSOD) or mannose-binding plant lectin Pinellia pedatisecta agglutinin (PPA), forming Ad.IL3-MnSOD and Ad.IL3-PPA. As compared with Ad.IL3 or Ad.sp-E1A control, Ad.IL3-MnSOD and Ad.IL3-PPA significantly suppressed in vitro proliferation of HL60 and KG-1 cells. Elevated apoptosis was detected in HL60 and KG-1 cells treated with either Ad.IL3-MnSOD or Ad.IL3-PPA. The caspase-9–caspase-7 pathway was determined to be activated by Ad.IL3-MnSOD as well as by Ad.IL3-PPA in HL60 cells. In an HL60/Luc xenograft nonobese diabetic/severe-combined immunodeficiency mice model, Ad.IL3-MnSOD and Ad.IL3-PPA suppressed cancer cell growth as compared with Ad.IL3. A significant difference of cancer cell burden was detected between Ad.IL3 and Ad.IL3-PPA groups at day 9 after treatment. Furthermore, Ad.IL3-MnSOD significantly prolonged mouse survival as compared with Ad.sp-E1A. These findings demonstrated that Ad.IL3-gene could serve as a novel agent for AML therapy. Harboring sCAR-ligand expression cassette in the viral genome may provide a universal method to redirect oncolytic adenoviruses to various membrane receptors on cancer cells resisting serotype 5 adenovirus infection.
Gardner's Syndrome with Glandular Cysts of the Fundic Mucosa
Authors: P. Eichenberger, B. Hammer, F. Gloor, S. Pelloni, R. Bossart
Journal: Endoscopy (1980)

The present study describes a family (mother and son) with Gardner's syndrome. Aside from the classical findings, gastric polyposis was found; histologically glandular cysts of the fundic mucosa were diagnosed. The occurrence of gastric polyps in Gardner's syndrome has recently been described with increasing frequency. These lesions have various histological aspects. A number of authors have noted several cases of Gardner's syndrome with glandular cysts of the fundic mucosa, but to our knowledge this is the first case of familial occurrence.
Dual targeting of EphA2 and ER restores tamoxifen sensitivity in ER/EphA2-positive breast cancer.
Authors: Y Gokmen-Polar, RA Toroni, S Badve, E Bruckheimer, MS Kinch, KD Miller
Journal: Cancer Research (2009)

Abstract Abstract #3020 Background: Overexpression and altered function of EphA2 receptor tyrosine kinase are critical in the progression of breast cancer and provide a novel target for breast cancer therapy. We have previously demonstrated that EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity both in vitro and in vivo. EA5, a novel monoclonal antibody that mimicks the binding of ephrin A to EphA2, reverses the effect of EphA2 overexpression and restores tamoxifen sensitivity in EphA2-transfected MCF-7 cells (MCF-7EphA2) in vitro. Here we report the impact of EA5 on in vivo tumor growth and its ability to overcome in vivo tamoxifen resistance in MCF-7EphA2 xenografts. Furthermore, we investigated the mechanisms by which EphA2 overexpression decreases the estrogen dependence and contributes to tamoxifen resistance in ER+ breast cancer models.&amp;#x2028; Material and Methods: MCF-7 cells transfected with vector (MCF-7neo) or EphA2 (MCF-7EphA2) were implanted in the right and left mammary fat pads of athymic mice. Treatment with EA5 (5 mg/kg/i.p./5 days/week), vehicle, tamoxifen (1 mg/oral gavage/5 days/week), or EA5 and tamoxifen in combination was initiated once tumors were established. To explore the role of EphA2 overexpression on ER-dependent mechanisms, we used two different ER+/EphA2-transfected cell line models (MCF-7neo/ MCF-7EphA2 and T47Dneo/ T47DEphA2). We measured ER activity and expression of ER-dependent proteins in response to 17β-estradiol (E2;10-10 M), 4-hydroxy-tamoxifen (10-6 M, and EA5 antibody (3μg/mL). Interaction of ER and EphA2 was investigated using GST-pulldown and co-immunoprecipitation approaches. Gene array studies suggested that EphA2 may impact ER via noncanonical pathways, leading to an investigation of focal adhesion kinase (FAK) signaling.&amp;#x2028; Results: EA5 inhibits primary tumor growth and restores tamoxifen sensitivity in the MCF-7EphA2 in vivo model;EA5 had no impact on in vivo tumor growth in MCF-7neo xenografts. Using T47DEphA2 in vitro model, we verified that EphA2 decreases ER activation in response to E2 stimulation consistent with our earlier results in MCF-7EphA2 model. We found no direct interaction between ER and EphA2 and no difference in expression of canonical ER-dependent proteins, ER coactivators or corepressors. However, E2 stimulation phosphorylates FAKTyr925 in ER+/EphA2+ cell lines but not in ER+/EphA2- cell lines. Treatment of T47DEphA2 cells with EA5 and tamoxifen leads to dephosphorylation of FAKTyr925 in the presence of E2 stimulation.&amp;#x2028; Conclusion: Our data demonstrate that dual targeting of EphA2 and ER is a promising approach for delaying resistance to tamoxifen. The data support our hypothesis that EphA2 impacts ER function via a FAK dependent pathway. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3020.
CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism
Authors: Antonella Zucchetto, Chiara Caldana, Dania Benedetti, Erika Tissino, Francesca Maria Rossi, Evelyn Hutterer, Federico Pozzo, Riccardo Bomben, Michele Dal Bo, Giovanni D’Arena, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Tanja N. Hartmann, Davide Rossi, Gianluca Gaidano, Giovanni Del Poeta, Valter Gattei
Journal: Blood (2013)
The inflammatory response in myocardial infarction
Authors: N Frangogiannis
Journal: Cardiovascular Research (2002)

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-α release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
Impaired Endothelium-Dependent Vasodilation of Coronary Resistance Vessels Is Associated With Exercise-Induced Myocardial Ischemia
Authors: Andreas M. Zeiher, Thomas Krause, Volker Schächinger, Jan Minners, Ernst Moser
Journal: Circulation (1995)

The release of endothelium-derived relaxing factors has been shown experimentally to be of pivotal importance for the maintenance of coronary blood flow during increased demand. In humans with coronary atherosclerosis, endothelial vasodilator dysfunction is not confined only to epicardial conductance vessels but may also extend into the coronary microcirculation. We therefore tested the hypothesis that endothelial vasodilator dysfunction of the coronary resistance vasculature is associated with myocardial ischemia during exercise in patients without hemodynamically significant epicardial artery stenoses.Coronary vasodilator function was assessed by subselective infusion of the endothelium-dependent dilator acetylcholine (0.036 to 3.6 micrograms/mL) and the endothelium-independent dilator papaverine (7 mg). Coronary blood flow responses were evaluated by intracoronary Doppler flow velocity recordings and quantitative angiography. Exercise-induced myocardial perfusion was determined by 201Tl single photon emission computed tomographic imaging. Thirteen patients had exercise-induced myocardial perfusion defects suggestive of myocardial ischemia, whereas 14 patients had normal thallium imaging during exercise. In patients with exercise-induced thallium perfusion defects, coronary blood flow responses to acetylcholine were significantly (P < .005) blunted compared with patients with normal thallium imaging during exercise. In contrast, coronary blood flow reserve to the endothelium-independent smooth muscle relaxant papaverine was similar in the two groups. Patients with exercise-induced thallium perfusion defects exhibited a significantly (P < .005) reduced (23.9 +/- 9.0% [mean +/- SD]) endothelium-mediated coronary vasodilator capacity compared with patients with normal thallium testing (56.2 +/- 27.8%). Epicardial artery vasoreactivity to acetylcholine did not differ between the two groups.Impaired endothelium-dependent vasodilation of the coronary microcirculation is associated with exercise-induced myocardial ischemia in patients without hemodynamically significant epicardial artery lesions. Endothelial vasodilator dysfunction extending into the coronary microcirculation may thus contribute to the ischemic manifestations of coronary artery disease during times of increased myocardial demand.
Controlled trial of slow-release aminophylline in childhood asthma: are short-term trials valid?
Authors: N Wilson, M Silverman
Journal: BMJ (1982)

Slow-release aminophylline, although widely used for the prophylaxis of childhood asthma, has had only limited formal assessment. A four-month double-blind cross-over trial of slow-release aminophylline (14 mg/kg twice daily) was carried out in 24 children with perennial asthma. Satisfactory serum theophylline concentrations were obtained in 17 children, with few side effects. There was a significant improvement in mild daytime and night-time symptoms. The incidence of more severe symptoms was unaffected. Treatment did not improve the mean peak expiratory flow or reduce the incidence of use of bronchodilators. It is concluded that slow-release aminophylline has a place in the prophylaxis of perennial childhood asthma but is unsuitable for children who suffer from severe attacks. The cross-over trial design has severe limitations.
The Wrong Way to Stay Slim
Authors: Joseph A. Califano
Journal: New England Journal of Medicine (1995)

In early 1977, as the newly appointed Secretary of Health, Education, and Welfare, I interviewed 150 top physicians and public health professionals for positions in the department and asked how each would mount a national health-promotion and disease-prevention campaign. Without exception, they responded that any serious health-promotion program must attack smoking front and center.How right they were. Despite the sharp decline in the proportion of Americans who smoke, we are still reaping the deadly harvest of decades of smoking. In 1995, more than 400,000 Americans will die from tobacco-related ailments such as lung cancer, emphysema, and heart disease1; . . .
How 21st century capitalism is failing us
Authors: R. Wilkinson, K. Pickett
Journal: BMJ (2014)

Peer review aims to ensure the quality and credibility of research reporting. Conducted by volunteer scientists who receive no guidance or direction, peer review widely varies from fast and facilitative, to unclear and obstructive. Poor quality is an issue because most science research is publicly funded, whereby scientists must make an effort to quickly disseminate their findings back to the public. An unfortunately not uncommon barrier in this process is ineffective peer review. Most scientists agree that when done well, editors and reviewers drive and maintain the high standards of science. At the same time, ineffective peer review can cause great delay with no introduced improvement in final product. These delays and requests interfere with the path of communication between scientist and public, at a great cost to editors, reviewers, authors and those who stand to benefit from application of the results of the studies. We offer a series of concrete recommendations to improve this process.
Syrian government defies principle of medical neutrality by targeting underground clinics
Authors: J. Gavin
Journal: BMJ (2011)

A prominent Syrian doctor who helped treat wounded protestors involved in the uprising against the regime of President Bashar al-Assad was found dead on 10 December, apparently shot by state security forces according to opposition sources.

Ibrahim Othman was a third year resident in orthopaedic surgery at Al-Mouassat University Hospital in Damascus. Originally from Hama—one of the centres of opposition activity—he graduated from Damascus University Medical School in 2009.

The 26 year old was a founder of Damascus Doctors, a network of doctors that secretly treats wounded protesters who are afraid to go to government run hospitals. He coordinated …
Clinical Practice Guideline Development and Antitrust Law
Authors: Richard Wolfram
Journal: JAMA (2009)

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
Sobering News About Booze
Authors: Joan Stephenson
Journal: JAMA (1999)

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