tbuckley/cabot-search huggingface dataset:
The type B brevetoxin (PbTx-3) adversely affects development, cardiovascular function, and survival in Medaka (Oryzias latipes) embryos.
Authors: Jamie R Colman, John S Ramsdell
Journal: Environmental Health Perspectives (2003)

Brevetoxins are produced by the red tide dinoflagellate Karenia brevis. The toxins are lipophilic polyether toxins that elicit a myriad of effects depending on the route of exposure and the target organism. Brevetoxins are therefore broadly toxic to marine and estuarine animals. By mimicking the maternal route of exposure to the oocytes in finfish, we characterized the adverse effects of the type B brevetoxin brevetoxin-3 (PbTx-3) on embryonic fish development and survival. The Japanese rice fish, medaka (Oryzias latipes), was used as the experimental model in which individual eggs were exposed via microinjection to various known concentrations of PbTx-3 dissolved in an oil vehicle. Embryos injected with doses exceeding 1.0 ng/egg displayed tachycardia, hyperkinetic twitches in the form of sustained convulsions, spinal curvature, clumping of the erythrocytes, and decreased hatching success. Furthermore, fish dosed with toxin were often unable to hatch in the classic tail-first fashion and emerged head first, which resulted in partial hatches and death. We determined that the LD(50) (dose that is lethal to 50% of the fish) for an injected dose of PbTx-3 is 4.0 ng/egg. The results of this study complement previous studies of the developmental toxicity of the type A brevetoxin brevetoxin-1 (PbTx-1), by illustrating in vivo the differing affinities of the two congeners for cardiac sodium channels. Consequently, we observed differing cardiovascular responses in the embryos, wherein embryos exposed to PbTx-3 exhibited persistent tachycardia, whereas embryos exposed to PbTx-1 displayed bradycardia, the onset of which was delayed.
Abstract 5065: Orally active nontoxic dual MMP2 and CAIX inhibitors as anticancer therapy.
Authors: Eli Breuer
Journal: Cancer Research (2013)

Abstract Carbonic anhydrases IX and XII, (CAIX and CAXII) are critical to maintain a low pH in the tumor cell's microenvironment, and MMP-2 is critical for breaching the basement membrane that opens the way to the dissemination of metastases. The expression of carbonic anhydrase IX (CAIX), a marker for hypoxic tumors, is correlated with poor prognosis. In this presentation, we wish to report that carbamoylphosphonates (CPOs) have been identified as orally bioavailable dual inhibitors of matrix metalloproteinase-2 (MMP-2) on the one hand, and carbonic anhydrases (CAs) on the other hand, especially the IX and XII isoforms, well known as cancer promoting factors. We have also demonstrated that the ionized CPO acids are unable to cross the cell membrane and thus are limited to interact with enzymes present in the extracellular domains of as are both CA isozymes CAIX and CAXII and MMP-2. Finally, exposing cancer cells to CPOs in hypoxic conditions resulted in the dose dependent release of lactate dehydrogenase, confirming the direct interaction of the CPOs with the cancer related isozymes CAIX and XII and thereby promoting cellular damage. Thus, CPOs can be regarded as novel orally active nontoxic drug candidates for CAIX expressing tumor targeted chemotherapy acting by two synergistic mechanisms, namely, inhibiting CAs and MMPs simultaneously. Citation Format: Eli Breuer. Orally active nontoxic dual MMP2 and CAIX inhibitors as anticancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5065. doi:10.1158/1538-7445.AM2013-5065
Administration of prostaglandin E1 analog reduces rat hepatic and ito cell collagen gene expression and collagen accumulation after bile duct ligation injury
Authors: David W. A. Beno, Ronald Espinal, Brian M. Edelstein, Bernard H. Davis
Journal: Hepatology (1993)

Recent studies suggest that prostaglandin E may have the ability to suppress cytokine responsiveness. We examined the effects of prostaglandin E administration on several parameters of acute and chronic liver injury induced by bile duct ligation. Enisoprost, a prostaglandin E1 analog, was found to suppress early hepatic and Ito cell type I collagen gene expression without diminishing the induction of the fibrogenic cytokine transforming growth factor-beta. Overall liver inflammation and cell proliferation were not altered, suggesting that prostaglandin E acts distal to the initial injurious event(s). During later phases, drug administration reduced total collagen accumulation and type I collagen periductular infiltration associated with early nodule formation.
Comparing Severity and Outcomes for Seasonal and 2009 H1N1 Infections—Reply
Authors: Edward A. Belongia
Journal: JAMA (2011)

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
Contribution of Na+/H+ exchange to Na+ overload in the ischemic hypertrophied hyperthyroid rat heart
Authors: M Bak
Journal: Cardiovascular Research (2003)

The mechanisms responsible for intracellular ion homeostasis in ischemic hypertrophied myocardium are not fully known. Moderately hypertrophied hyperthyroid hearts (T3) are characterized by the bioenergetic changes and increased Na+/H+ exchange (NHE) activity comparable with those observed in humans and experimental models of hypertrophy. Here we test the hypothesis whether NHE inhibition in T3 heart improves ion homeostasis during ischemia and contractile function during recovery.We compared intracellular H+ (H+i) and Na+ (Na+i) accumulations during 28 min global ischemia in isolated perfused T3 and euthyroid (EUT) rat hearts with and without NHE inhibition by using 31P and 23Na NMR. Heart function was measured during control perfusion and 30 min following ischemic insult.In T3 hearts ischemia caused: (1) faster and greater Na+i accumulation (534+/-25% of preischemic level versus 316+/-22% in EUT, P<0.001); (2) lower acidification (pH(i) 6.66+/-0.66 versus 6.12+/-0.12 in EUT, P<0.001); and (3) faster hydrolysis of ATP. NHE inhibition (amiloride 1 mM) in T3 hearts lead to: (1) delayed and lower Na+i accumulation by 35+/-5%; (2) faster and greater acidification (pH(i) 6.45+/-0.15, P<0.05); (3) delayed ATP degradation; and (4) improved heart function during recovery. When NHE was inhibited, all T3 hearts (n=11) recovered 68+/-10% of their preischemic rate pressure product (RPP), while only two untreated T3 hearts (from 11) recovered approximately 40% of preischemic RPP.These data suggest that NHE inhibition could be useful intervention for the prevention of ischemic/reperfusion cell injury and could improve the function of the hypertrophied heart after acute ischemia.
Plasma Renin After Renal Homotransplantation.
Authors: James A. Greene
Journal: Annals of Internal Medicine (1967)

s1 May 1967Plasma Renin After Renal Homotransplantation.James A. Greene Jr., M.D., Arthur Vander, M.D.James A. Greene Jr., M.D.Search for more papers by this author, Arthur Vander, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1050_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn order to evaluate the role of the renal nerves in the renal response to sodium restriction and to the upright posture, three patients who had renal homotransplants 1 or more years previously and their kidney donors were studied. One pair were identical twins, and the others were close relatives. Blood for renin determinations was taken daily at 10AMafter the patient had been sitting for 2 hr. After being on a 100-mEq sodium diet for a minimum of 3 days, they were placed on a 10-mEq sodium diet for 5 days. All patients responded with a fall in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: James A. GreeneJr., M.D.; Arthur Vander, M.D.Affiliations: Ann Arbor, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1050-1050KeywordsBloodBlood plasmaDietFallsHomotransplantationKidneysMonozygotic twinsNervesPostural controlSodium ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Partial purification and characterization of contact activation cofactor.
Authors: S Schiffman, P Lee
Journal: Journal of Clinical Investigation (1975)

The contact phase of intrinsic clotting involves Factor XI, Factor XII, Fletcher factor, and a fourth activity that we call contact activation cofactor (CAC). All four of these activities are reduced or absent in Dicalite-adsorbed plasma. A modified activated partial thromboplastin time assay for CAC has been defined by using a substrate of Dicalite-adsorbed plasma combined with partially purified sources of Factors XI and XII, and Fletcher factor. The following properties of CAC in plasma have been determined by using the assay: it is stable up to 60 min at 56 degrees C; gradually loses activity at 80 degrees C; is stable between pH 6 and 9; is precipitated by ammonium sulfate between 40% and 50% saturation; is slightly adsorbed by A1(OH)3; and is eluted from DEAE-cellulose after the major protein peaks. A purification procedure has been devised that separates CAC from other known clotting factors. Isolated CAC was less stable than CAC in plasma, but in the presence of dilute human serum albumin it retained full activity for 80 min at 56 degrees C. On gel filtration CAC had an apparent mol wt of 220,000 daltons. These properties are consistent with those described for Fitzgerald factor, which further supports the conclusion that CAC and Fitzgerald factor represent the same activity. Isolated CAC promoted the generation of activated Factor XI (XIa) in a mixture containing purified Factor XI, Factor XII, and kaolin. The amount of Factor XIa generated was proportional to the amount of added CAC. No time-consuming reaction between Factor XI or Factor XII and CAC could be demonstrated.
NPAS1 Represses the Generation of Specific Subtypes of Cortical Interneurons
Authors: Amelia Stanco, Ramón Pla, Daniel Vogt, Yiran Chen, Shyamali Mandal, Jamie Walker, Robert F. Hunt, Susan Lindtner, Carolyn A. Erdman, Andrew A. Pieper, Steven P. Hamilton, Duan Xu, Scott C. Baraban, John L.R. Rubenstein
Journal: Neuron (2014)
Atlas of Anatomay
Authors: R. J. Harrison
Journal: BMJ (1964)

The dopaminergic mechanisms that control reward-motivated behavior are the subject of intense study, but it is yet unclear how, in humans, neural activity in mesolimbic reward-circuitry and its functional neuroimaging correlates are related to dopamine release. To address this question, we obtained functional magnetic resonance imaging (fMRI) measures of reward-related neural activity and [<sup>11</sup>C]raclopride positron emission tomography measures of dopamine release in the same human participants, while they performed a delayed monetary incentive task. Across the cohort, a positive correlation emerged between neural activity of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic neurotransmission, during reward anticipation and reward-related [<sup>11</sup>C]raclopride displacement as an index of dopamine release in the ventral striatum, major target of SN/VTA dopamine neurons. Neural activity in the ventral striatum/nucleus accumbens itself also correlated with ventral striatal dopamine release. Additionally, high-reward-related dopamine release was associated with increased activation of limbic structures, such as the amygdala and the hippocampus. The observed correlations of reward-related mesolimbic fMRI activation and dopamine release provide evidence that dopaminergic neurotransmission plays a quantitative role in human mesolimbic reward processing. Moreover, the combined neurochemical and hemodynamic imaging approach used here opens up new perspectives for the investigation of molecular mechanisms underlying human cognition.
Screening for diabetes: what are we really doing?
Authors: E. Goyder, L. Irwig
Journal: BMJ (1998)

#### Summary points

Current recommendations for diabetes screening suggest that screening decisions should be based on the risk of diabetes itself

However, it is more logical to base screening and treatment decisions on the risk of microvascular and macrovascular complications that can be prevented effectively by early intervention

People with diabetes detected by screening are at high risk of macrovascular disease and comparatively low risk of microvascular complications

Early treatment for other macrovascular risk factors may be more important than early treatment for diabetes itself

With no direct evidence of long term benefit from randomised controlled trials in screened populations, we used Medline and the Cochrane Library to identify randomised controlled trials that included populations with clinical diabetes and reported long term outcomes. We also used a model of clinical non-insulin dependent diabetes to estimate outcomes in the absence of screening. 8 9

Most current screening guidelines and recommendations use a model of disease screening when they suggest screening for diabetes. Research has focused on establishing the sensitivity and specificity of different tests, and tends to measure the success of a diabetes screening programme in terms of the number of new cases identified.10–12

One problem with focusing on case detection is that the potential benefit of screening is not similar for all cases. The risk of microvascular complications increases with the plasma glucose concentration and the duration of diabetes, while the risk of macrovascular disease depends on age, sex, genes, and lifestyle, as well as hyperglycaemia. As an increased risk of macrovascular disease may occur in people whose plasma glucose concentration is lower than values found in diabetes, it is difficult to identify a single …
Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots
Authors: Giancarlo la Marca, Clementina Canessa, Elisa Giocaliere, Francesca Romano, Sabrina Malvagia, Silvia Funghini, Maria Moriondo, Claudia Valleriani, Francesca Lippi, Daniela Ombrone, Maria Luisa Della Bona, Carsten Speckmann, Stephan Borte, Nicholas Brodszki, Andrew R. Gennery, Katja Weinacht, Fatih Celmeli, Julia Pagel, Maurizio de Martino, Renzo Guerrini, Helmut Wittkowski, Ines Santisteban, Pawan Bali, Aydan Ikinciogullari, Michael Hershfield, Luigi D. Notarangelo, Massimo Resti, Chiara Azzari
Journal: Journal of Allergy and Clinical Immunology (2014)
Prognostic significance of location and type of myocardial infarction: Independent adverse outcome associated with anterior location
Authors: Peter H Stone, Daniel S Raabe, Allan S Jaffe, Nancy Gustafson, James E Muller, Zoltan G Turi, John D Rutherford, W.Kenneth Poole, Eugene Passamani, James T Willerson, Burton E Sobel, Thomas Robertson, Eugene Braunwald
Journal: Journal of the American College of Cardiology (1988)
A novel SCN5A mutation manifests as a malignant form of long QT syndrome with perinatal onset of tachycardia/bradycardia
Authors: C CHANG, S ACHARFI, M WU, F CHIANG, J WANG, T SUNG, M CHAHINE
Journal: Cardiovascular Research (2004)

Objective: Congenital long QT syndrome (LQTS) with in utero onset of the rhythm disturbances is associated with a poor prognosis. In this study we investigated a newborn patient with fetal bradycardia, 2:1 atrioventricular block and ventricular tachycardia soon after birth.
FIBROID TUMORS OF THE UTERUS.A STUDY OF THE DEGENERATIONS AND COMPLICATIONS IN TWENTY-TWO HUNDRED AND SEVENTY-FOUR CASES,† ALSO A STUDY OF FORTY-EIGHT HUNDRED AND EIGHTY CONSECUTIVE CASES IN THEIR RELATION TO CARCINOMA AND SARCOMA OF THE UTERUS.
Authors: CHARLES P. NOBLE
Journal: JAMA (1906)

As early as 1894, as a result of the observation of the clinical history of women suffering from fibroid tumors, I became convinced of the fallacy of the classical teachings concerning the natural history of these tumors. At that time I had operated on but thirty women suffering from fibroid tumors. In the conclusion of a paper read in 1894,<sup>1</sup>I said: The comparatively small number of operations which I have done for fibroid tumors is evidence of the fact that for a long time I was profoundly influenced in my practice by the classical teaching concerning this disease. It was not until my own observations convinced me of the fallacies of the past teaching that I felt justified in resorting to the removal of fibroid tumors except in the worst class of cases. I am coming more and more to believe, however, that it is the part of
Doctor's Heart
Authors: George Stetten
Journal: JAMA (1995)

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
Fibrillar Collagen Specifically Regulates Human Vascular Smooth Muscle Cell Genes Involved in Cellular Responses and the Pericellular Matrix Environment
Authors: Takuya Ichii, Hidenori Koyama, Shinji Tanaka, Shokei Kim, Atsushi Shioi, Yasuhisa Okuno, Elaine W. Raines, Hiroshi Iwao, Shuzo Otani, Yoshiki Nishizawa
Journal: Circulation Research (2001)

Abstract —Proliferation and α v β 3 integrin–dependent migration of vascular smooth muscle cells are suppressed on polymerized type I collagen. To identify genes specifically regulated in human smooth muscle cells by polymerized collagen, we used the suppressive subtraction hybridization technique. Compared with smooth muscle cells cultured on monomer collagen, polymerized collagen suppresses the following: (1) a number of other extracellular matrix proteins, including fibronectin, thrombospondin-1, tenascin-C, and cysteine-rich protein 61; (2) actin binding proteins including α-actinin; (3) signaling molecules; (4) protein synthesis–associated proteins; and (5) genes with unknown functions. Some of the identified genes, including cysteine-rich protein 61, show unique kinetics of mRNA regulation by monomer or polymerized collagen distinct from growth factors, suggesting extracellular matrix–specific gene modulation. Moreover, in vivo balloon catheter–mediated injury to the rat carotid artery induces many of the genes that are suppressed by polymerized collagen. Protein levels of thrombospondin-1 and fibronectin are also suppressed by polymerized collagen. Thrombospondin-1–mediated smooth muscle cell migration on vitronectin is significantly inhibited after culture on polymerized collagen for 24 hours, which is associated with decreased α-actinin accumulation at focal adhesions. Thus, polymerized type I collagen dynamically regulates gene expression, pericellular accumulation of extracellular matrix molecules, and the response to a given matrix molecule.
Treatment of experimental encephalomyelitis with a novel chimeric fusion protein of myelin basic protein and proteolipid protein.
Authors: E A Elliott, H I McFarland, S H Nye, R Cofiell, T M Wilson, J A Wilkins, S P Squinto, L A Matis, J P Mueller
Journal: Journal of Clinical Investigation (1996)

It has been shown that peripheral T cell tolerance can be induced by systemic antigen administration. We have been interested in using this phenomenon to develop antigen-specific immunotherapies for T cell-mediated autoimmune diseases. In patients with the demyelinating disease multiple sclerosis (MS), multiple potentially autoantigenic epitopes have been identified on the two major proteins of the myelin sheath, myelin basic protein (MBP) and proteolipid protein (PLP). To generate a tolerogenic protein for the therapy of patients with MS, we have produced a protein fusion between the 21.5-kD isoform of MBP (MBP21.5) and a genetically engineered form of PLP (deltaPLP4). In this report, we describe the effects of treatment with this agent (MP4) on clinical disease in a murine model of demyelinating disease, experimental autoimmune encephalomyelitis (EAE). Treatment of SJL/J mice with MP4 after induction of EAE either by active immunization or by adoptive transfer of activated T cells completely prevented subsequent clinical paralysis. Importantly, the administration of MP4 completely suppressed the development of EAE initiated by the cotransfer of both MBP- and PLP-activated T cells. Prevention of clinical disease after the intravenous injection of MP4 was paralleled by the formation of long-lived functional peptide-MHC complexes in vivo, as well as by a significant reduction in both MBP- and PLP-specific T cell proliferative responses. Mice treated with MP4 were resistant to disease when rechallenged with an encephalitogenic PLP peptide emulsified in CFA, indicating that MP4 administration had a prolonged effect in vivo. Administration of MP4 was also found to markedly ameliorate the course of established clinical disease. Finally, MP4 therapy was equally efficacious in mice defective in Fas expression. These results support the conclusion that MP4 protein is highly effective in suppressing disease caused by multiple neuroantigen epitopes in experimentally induced demyelinating disease.