tbuckley/cabot-search huggingface dataset:
Relationship of contractile state to ejection performance in patients with chronic aortic valve disease.
Authors: T Wisenbaugh, D Booth, A DeMaria, S Nissen, J Waters
Journal: Circulation (1986)

To assess the relative contributions of afterload mismatch and impaired contractility to pump dysfunction in patients with chronic aortic valve disease, simultaneous left ventricular cineangiography and micromanometry were performed in 56 patients: 21 with severe aortic stenosis, 16 with severe aortic regurgitation, and 19 normal control subjects. Left ventricular mass was increased in patients with aortic stenosis and aortic regurgitation (172 +/- 52 and 224 +/- 63 g/m2, respectively, vs 89 +/- 16 for control subjects; p less than .05) as were end-diastolic volume (101 +/- 39 and 167 +/- 44 vs 77 +/- 16 ml/m2; p less than .05) and end-systolic volume (50 +/- 40 and 84 +/- 43 vs 24 +/- 7 ml/m2; p less than .05). Although ejection fraction was depressed in both abnormal groups (0.56 +/- 0.18 for patients with aortic stenosis and 0.53 +/- 0.13 for those with aortic regurgitation vs 0.69 +/- 0.05 for control subjects; p less than .05), the decrease in ejection fraction was disproportionate to the mild degree of afterload mismatch (end ejection stress 129 +/- 17 in patients with aortic stenosis and 154 +/- 58 in those with aortic regurgitation vs 117 +/- 46 kdyn/cm2 in control subjects; p = NS) with 10 of 21 patients with aortic stenosis and 12 of 16 patients with aortic regurgitation falling below the 95% prediction limit of the linear inverse relationship between ejection fraction and end-systolic stress for controls (EF = 0.78 - 0.00074 X ESS).(ABSTRACT TRUNCATED AT 250 WORDS)
The Conjunctival Sign in Sickle Cell Anemia
Authors: Graham R. Serjeant
Journal: JAMA (1972)

Patients with homozygous sickle cell disease were divided into five groups according to the extent of abnormal vessels in the conjunctival vasculature. There was a significant relationship between the grade of abnormality and the number of irreversibly sickled cells, suggesting that these cells may be related to the genesis of these vessel anomalies. Evidence is accumulating that irreversibly sickled cells are related to several pathological processes in sickle cell anemia, and we believe the sign may be useful not only in suggesting the diagnosis but also in gauging the severity of the condition.
Abstract 2012: Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in the GALAXY TrialTM (NCT01348126): a randomized phase IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects wit
Authors: Dean Anthony Fennell, L. Miguel Martins, Iman El-Hariry, Vojo Vukovic, Florentina Teofilovici, Vienna L. Reichert, Jacqui Shaw
Journal: Cancer Research (2013)

Abstract Background: Non-small cell lung cancer is a mosaic, comprising several distinct molecular subtypes driven by somatic mutations in so-called cancer genes. Several of these oncogenic mutations confer dependence on HSP90 e.g. EML4-ALK, BRAF, KRAS, KIT. Inhibition of Hsp90 induces apoptosis and can exploit this dependence. Ganetespib (G) is an Hsp90 inhibitor with single agent activity in molecularly defined disease, including EML4-ALK rearrangement, KRAS mutations, HER2 amplification and BRAF mutations. Circulating free DNA (cfDNA) is present at low levels in plasma of healthy individuals allowing detection of somatic mutations by deep sequencing. The aim of this work was to determine the mutational spectrum of patients enrolled into the GALAXY trial using this liquid biopsy strategy. Methods: We performed a prospective exploratory analysis to identify plasma-borne somatic mutations as predictors of clinical outcome with G in GALAXY, a randomized trial, comparing G + docetaxel (D), to D alone in 2nd line advanced NSCLC patients. Plasma samples were collected from approximately 200 patients with adenocarcinoma at baseline prior to initiation of treatment, and during cycles 1 and 2. cfDNA samples were evaluated using the Ion AmpliSeq™ Cancer Panel on the Ion Torrent |PGM platform to survey 739 amplicons in 46 cancer genes at up to 6000x depth. Results: CfDNA targeted sequence analysis of the first 38 patients revealed multiple concurrent mutations in client proteins including the HSP90 client proteins BRAF, PDGFR and KIT, demonstrating the feasibility of this method. Sequencing of a larger cohort is underway. Longitudinal sampling of plasma has been conducted to monitor temporal evolution of the penetrance of mutations. Summary: Ultra-deep re-sequencing of multiple somatic mutations in circulating cfDNA is feasible, and can potentially enable identification of G sensitive subgroups. This represents a new approach to biomarker discovery in the context of phase II trials. Citation Format: Dean Anthony Fennell, L. Miguel Martins, Iman El-Hariry, Vojo Vukovic, Florentina Teofilovici, Vienna L. Reichert, Jacqui Shaw. Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in the GALAXY TrialTM (NCT01348126): a randomized phase IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects wit [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 2012. doi:10.1158/1538-7445.AM2013-2012
Intestinal permeability assessed by excretion ratios of two molecules: results in coeliac disease.
Authors: I Cobden, R J Dickinson, J Rothwell, A T Axon
Journal: BMJ (1978)

In this patient it merged into what, in retrospect, was the first symptom of the shoulder-hand syndrome.Whether the pain itself or the resulting immobility with impairment of the venous and lymphatic pumping mechanism4 triggers the development of the syndrome is unknown, but in any event it seems that laparoscopic sterilisation can be added to the long list of potential precipitating factors.'The history of psychiatric illness in this patient may also be relevant.5As this case shows, the illness can be lengthy, disabling, and resistant to treatment, particularly when diagnosis is delayed.2 3 The syndrome is uncommon, particularly in young people,2 and early diagnosis will depend on being alert to the possibility.
129. Development of Vectors Utilizing Strong Neuronal Cell Type Specific Promoters for High Level Expression of Beta Glucuronidase in the Central Nervous System
Authors: Tupur Husain, John H. Wolfe
Journal: Molecular Therapy (2005)

Recombinant adeno-associated viruses (AAV) are promising vectors for delivery to the central nervous system, e.g. in lysosomal storage disorder such as GUSB-deficient MPS VII. The cellular tropism of AAV gene delivery varies depending on the serotype used. In lysosomal enzyme deficient cells, the transferred normal enzyme is secreted and can be endocytosed by adjacent cells (sphere of correction). Although treatments have been shown to work in mouse brains, enzyme delivery will need to be significantly increased to produce the same effect in larger brains such as humans. Our laboratory has shown that the level of GUSB expression and secretion is proportional to increased transcription from vectors. Various promoters have been known to modulate different levels of transcription in the CNS. If vector-mediated gene delivery could produce higher levels of enzyme secretion from a minimal number of injections, the sphere of correction could be increased for enzyme diffusion, axonal transport, and migrating cross-correcting cells. We have designed a eukaryotic minigene vector driven by the natural promoter. The vector contains the first two introns in addition to all the exon sequences of hGUSB. Mouse brains were stereotactically injected into the left midbrain region with 2.5 |[times]| 1012 viral genome equivalents per each of four injection sites. The major structures injected were the cortex, striatum, hippocampus and thalamus. The pattern of transduction at 2 months post-injection was assessed by in situ hybridization which shows similar patterns of transduction to a control vector without introns in the cortex, striatum, hippocampus and thalamus. Quantitative measurements for transcription are in progress. The enzyme positive cells were detected at the sites of injection and further extended beyond the regions of transduced cells when rostral and caudal sections were examined. GUSB enzyme in the hippocampus was also detected in the contralateral region of the hippocampus. Experiments are also in progress to test the neuron-specific enolase (NSE) and latency associated (LAT) promoters. The NSE promoter has been known to confer high levels of gene expression when used in recombinant AAV2 vectors in transduced neurons, and has been found to express therapeutic levels of enzyme in other MPS models. In herpesviruses, the LAT promoter is the only viral gene sequence expressed in life-long latent infections in post-mitotic neurons. It has also been shown that significantly more GUSB activity is detected when the GUSB cDNA is inserted near the LAT promoter as opposed to other lower transcriptional level configurations. Evaluation of the effects of the NSE promoter and HSV-LAT promoter in the transcriptional high level configuration for GUSB are currently in progress for comparison with the hGUSB minigene and cDNA vector controls.
Apolipoproteins E and AV mediate lipoprotein clearance by hepatic proteoglycans
Authors: Jon C. Gonzales, Philip L.S.M. Gordts, Erin M. Foley, Jeffrey D. Esko
Journal: Journal of Clinical Investigation (2013)

The heparan sulfate proteoglycan (HSPG) syndecan-1 (SDC1) acts as a major receptor for triglyceride-rich lipoprotein (TRL) clearance in the liver. We sought to identify the relevant apolipoproteins on TRLs that mediate binding to SDC1 and determine their clinical relevance. Evidence supporting ApoE as a major determinant arose from its enrichment in TRLs from mice defective in hepatic heparan sulfate (Ndst1f/fAlbCre⁺ mice), decreased binding of ApoE-deficient TRLs to HSPGs on human hepatoma cells, and decreased clearance of ApoE-deficient [³H]TRLs in vivo. Evidence for a second ligand was suggested by the faster clearance of ApoE-deficient TRLs after injection into WT Ndst1f/fAlbCre⁻ versus mutant Ndst1f/fAlbCre⁺ mice and elevated fasting and postprandial plasma triglycerides in compound Apoe⁻/⁻Ndst1f/fAlbCre⁺ mice compared with either single mutant. ApoAV emerged as a candidate based on 6-fold enrichment of ApoAV in TRLs accumulating in Ndst1f/fAlbCre⁺ mice, decreased binding of TRLs to proteoglycans after depletion of ApoAV or addition of anti-ApoAV mAb, and decreased heparan sulfate-dependent binding of ApoAV-deficient particles to hepatocytes. Importantly, disruption of hepatic heparan sulfate-mediated clearance increased atherosclerosis. We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV.
Articles Published by Dr. F. F. Friedmann
Authors: O. H. Perry Pepper
Journal: JAMA (1913)

<h3>To the Editor:</h3> —Although the medical profession of this country may not be favorably impressed to-day with the claims made by Friedmann, and although he has not definitely announced whether the substance he is now using is the same as the culture employed in his earlier experiments or derived from it, yet it is of interest to review briefly his original articles. The first publications by Friedmann concerning this subject appeared in the year 1903 and were four in number, the earliest entitled "Spontaneous Pulmonary Tuberculosis with Large Cavity in a Turtle (Chelone Corticata)" (Spontane Lungentuberkulose mit grosser Kaverne bei einer Wasserschildkröte [Chelone corticata],<i>Deutsch. med. Wchnschr</i>., Jan. 8, 1903). In this article Friedmann states that except for an occasional dubious report there had previously been no description of an authentic case of spontaneous tuberculosis of the lungs in a cold-blooded animal. The case he reports, which he asserts was
Abbreviations Raise Their Pointy Heads Again: Familiarity Breeds Contretemps. Should We Bench Bench?
Authors: John S. Schweppe
Journal: JAMA (1991)

To the Editor.  —Increasingly in JAMA articles you use a given name of a drug or technique followed by an abbreviation and carry the abbreviation throughout the article. It is difficult to decipher and remember the abbreviation. For example, C/AMP is a common abbreviation in oncology and biochemistry. However, DDI, a drug used to treat AIDS, is relatively unknown. May I suggest that the specific or generic word be spelled out if it is not frequently used?  Authors also use the antiquated term laboratory bench . We work in modern laboratories shielded from contaminating chemical or viral-bacterial material. It should not be labeled a bench.  In short, let us use the scientific media with well-written, easy-to-interpret terminology and write briefly, concisely, and clearly. We should write scientifically but with fluidity.
Hidradenitis Suppurativa
Authors: Vanessa L. Pascoe, Alexandra B. Kimball
Journal: JAMA Dermatology (2014)

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
NICE replies to concerns about scanning patients with head injury who are taking anticoagulants and antiplatelet drugs
Authors: C. Sharpin, S. Hodgkinson, V. Pollit, F. Lecky
Journal: BMJ (2014)

Recent National Institute for Health and Care Excellence (NICE) guidelines recommended computed tomography for patients with head injury who are taking warfarin. We understand Heywood’s concerns that other anticoagulants and antiplatelet drugs were not included.1 2 The …
Injury of the Human Diaphragm Associated with Exertion and Chronic Obstructive Pulmonary Disease
Authors: MAURICIO OROZCO-LEVI, JOSEP LLORETA, JOAN MINGUELLA, SERGI SERRANO, JOAN M. BROQUETAS, JOAQUIM GEA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Injury of the diaphragm may have clinical relevance having been reported in cases of sudden infant death syndrome or fatal asthma. However, examination of diaphragm injury after acute inspiratory loading has not been reported. The purpose of this study was to determine whether an acute inspiratory overload induces injury of the human diaphragm and to determine if diaphragm from chronic obstructive pulmonary disease (COPD) is more susceptible to injury. Eighteen patients with COPD and 11 control patients with normal pulmonary function (62 +/- 10 yr) undergoing thoracotomy or laparotomy were studied. A threshold inspiratory loading test was performed prior to surgery in a subset of seven patients with COPD and five control patients. Samples of the costal diaphragm were obtained during surgery and processed for electron microscopy analysis. Signs of sarcomere disruption were found in all diaphragm samples. The range of values of sarcomere disruption was wide (density: 2-45 abnormal areas/100 microm(2); area fractions: 1.3-17.3%), significantly higher in diaphragm from patients with COPD (p < 0.05) and with the greatest injury after inspiratory loading. We conclude that sarcomere disruption is common in the human diaphragm, is more evident in patients with COPD, and is higher after inspiratory loading, especially in the diaphragm of those with COPD.
A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing
Authors: Linda Madisen, Tianyi Mao, Henner Koch, Jia-min Zhuo, Antal Berenyi, Shigeyoshi Fujisawa, Yun-Wei A Hsu, Alfredo J Garcia, Xuan Gu, Sebastien Zanella, Jolene Kidney, Hong Gu, Yimei Mao, Bryan M Hooks, Edward S Boyden, György Buzsáki, Jan Marino Ramirez, Allan R Jones, Karel Svoboda, Xue Han, Eric E Turner, Hongkui Zeng
Journal: Nature Neuroscience (2012)
Toxicology of chlorofluorocarbon replacements.
Authors: W Dekant
Journal: Environmental Health Perspectives (1996)

Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements.
NOX2-derived reactive oxygen species are crucial for CD29-induced pro-survival signalling in cardiomyocytes
Authors: Berit I. Rosc-Schlüter, Stéphanie P. Häuselmann, Vera Lorenz, Michika Mochizuki, Federica Facciotti, Otmar Pfister, Gabriela M. Kuster
Journal: Cardiovascular Research (2011)

The highly expressed cell adhesion receptor CD29 (β(1)-integrin) is essential for cardiomyocyte growth and survival, and its loss of function causes severe heart disease. However, CD29-induced signalling in cardiomyocytes is ill defined and may involve reactive oxygen species (ROS). A decisive source of cardiac ROS is the abundant NADPH oxidase (NOX) isoform NOX2. Because understanding of NOX-derived ROS in the heart is still poor, we sought to test the role of ROS and NOX in CD29-induced survival signalling in cardiomyocytes.In neonatal rat ventricular myocytes, CD29 activation induced intracellular ROS formation (oxidative burst) as assessed by flow cytometry using the redox-sensitive fluorescent dye dichlorodihydrofluorescein diacetate. This burst was inhibited by apocynin and diphenylene iodonium. Further, activation of CD29 enhanced NOX activity (lucigenin-enhanced chemiluminescence) and activated the MEK/ERK and PI3K/Akt survival pathways. CD29 also induced phosphorylation of the inhibitory Ser9 on the pro-apoptotic kinase glycogen synthase kinase-3β in a PI3K/Akt- and MEK-dependent manner, and improved cardiomyocyte viability under conditions of oxidative stress. The ROS scavenger MnTMPyP or adenoviral co-overexpression of the antioxidant enzymes superoxide dismutase and catalase inhibited CD29-induced pro-survival signalling. Further, CD29-induced protective pathways were lost in mouse cardiomyocytes deficient for NOX2 or functional p47(phox), a regulatory subunit of NOX.p47(phox)-dependent, NOX2-derived ROS are mandatory for CD29-induced pro-survival signalling in cardiomyocytes. These findings go in line with a growing body of evidence suggesting that ROS can be beneficial to the cell and support a crucial role for NOX2-derived ROS in cell survival in the heart.
Haemodialysis-triggered asthma.
Authors: P Aljama, P Brown, P Turner, M K Ward, D N Kerr
Journal: BMJ (1978)

prevalence of epilepsy of 0-5 '.TIhc difference in the prevalence comparing the epilepsy between the two groups was significant (P-0.01,/2 test).'We are grateful to Dr P Kennedy for his help in assessing the epileptics;to Dr G Salmon, LDr J Bamforth, and Professor Ralph Wright for allowing us to study patients under their care.
The "Black Beard" Sign of Monostotic Paget??s Disease of the Mandible
Authors: JAMES C. MAILANDER
Journal: Clinical Nuclear Medicine (1986)

Paget's disease of bone can occur in up to 4% of the population over forty. Most of these patients are asymptomatic, and will have more than one bone involved. The monostotic presentation of the disease is much less common, but not rare. Monostotic Paget's disease involving the mandible, however, is very unusual. Only six cases have been reported since 1945, and bone imaging did not play a significant role in the diagnoses of these reports. A patient with proven Paget's disease of the mandible presented with a rather dramatic “bearded” image on a bone scan.
Persistence of hepatitis A vaccine induced seropositivity in infants and young children by maternal antibody status: 10-year follow-up
Authors: Umid M. Sharapov, Lisa R. Bulkow, Susan E. Negus, Philip R. Spradling, Chriss Homan, Jan Drobeniuc, Michael Bruce, Saleem Kamili, Dale J. Hu, Brian J. McMahon
Journal: Hepatology (2012)

Persistence of seropositivity conferred by hepatitis A vaccine administered to children &lt;2 years of age is unknown and passively transferred maternal antibodies to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response to the vaccine. One hundred ninety-seven infants and young children were randomized into three groups to receive a two-dose hepatitis A vaccine: group 1 at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months of age. Within each group, infants were randomized by maternal anti-HAV status. Anti-HAV levels were measured at 1 and 6 months and at 3, 5, 7, and 10 years after the second dose of hepatitis A vaccination. Children in all groups had evidence of seroprotection (&gt;10 mIU/mL) at 1 month after the second dose. At 10 years, all children retained seroprotective anti-HAV levels except for only 7% and 11% of children in group 1 born to anti-HAV–negative and anti-HAV–positive mothers, respectively, and 4% of group 3 children born to anti-HAV–negative mothers. At 10 years, children born to anti-HAV–negative mothers in group 3 had the highest geometric mean concentration (GMC) (97 mIU/mL; 95% confidence interval, 71-133 mIU/mL) and children born to anti-HAV–positive mothers in group 1 had the lowest GMC (29 mIU/mL; 95% confidence interval, 20-40 mIU/mL). Anti-HAV levels through 10 years of age correlated with initial peak anti-HAV levels (tested at 1 month after the second dose). Conclusion : The seropositivity induced by hepatitis A vaccine given to children &lt;2 years of age persists for at least 10 years regardless of presence of maternal anti-HAV. (HEPATOLOGY 2012)