tbuckley/cabot-search huggingface dataset:
P122Cardiac-specific deletion of Janus kinase 2 (JAK2) reveals marked cardiac pathology indicative of hypertrophy, heart failure and sudden cardiac death
Authors: X Gan, V Rajapurohitam, C Huang, J Xue, J Chow, M Karmazyn
Journal: Cardiovascular Research (2014)

Purpose: The Janus kinase 2 (JAK2) pathway plays an important role in cardiac signalling. Although the contribution of JAK2 to cardiac pathology is unclear, the failing human myocardium is associated with depressed JAK2-dependent STAT3 activation. We therefore studied the consequence of cardiac-specific JAK2 deletion on the heart. Methods. As global JAK2 deletion is embryonic-lethal, we generated mice with cardiac-specific disruption of the JAK2 gene using the Cre-loxP system in which homozygous Jak2 fl/fl mice were mated to heterozygous α-MHC Cre+/- mice. These mice (JAK2-KO) survived to birth, were visibly indistinguishable from their wild type littermate (JAK2-WT) controls and demonstrated cardiac specific JAK2 deletion determined by genotyping and Western blotting. Mice were followed for 4 months after birth and analyzed monthly by serial echocardiography. Other animals were sacrificed monthly and hearts were analyzed for cardiac-specific changes. Results. Body weights of KO and WT mice were identical although heart weights in KO mice were higher as was the expression of two molecular markers of hypertrophy, ANP and α-skeletal actin. Moreover, serial echocardiography revealed progressive deterioration of left ventricular (LV) function including a reduction in ejection fraction (at 4 months: 73 ± 2.5% in WT vs 33 ± 3.3% in KO, P<0.01). Other indices (all values at 4 months) including fractional shortening (41 ± 2.4% in WT vs 22 ± 1.9% in KO, P<0.01), cardiac output (12.3 ± 4.0 ml/min in WT vs 4.7 ± 0.7 ml/min in KO, P<0.05) and stroke volume (23.4 ± 5.8 μl in WT vs 10.8 ± 1.8 μl in KO, P<0.05) were equally depressed in JAK2-KO mice throughout the 4 month period. Kaplan-Meier analysis revealed mortality, likely due to sudden death, throughout the 4 month period which reached 42% at 4 months (P<0.05) with no deaths observed in JAK2-WT animals at any time. Hearts from JAK2-KO mice showed a significant reduction in STAT3 phosphorylation. In addition, myocardial immunofluorescence staining for connexin 43 was significantly reduced compared to WT mice. Hearts from these mice also showed a significant reduction in the protein expression levels of vinculin, a 117 kDa membrane bound protein which exerts important roles in cardiomyocyte integrity, function and cell-cell communication. Conclusions. Our results show for the first time that selective cardiac deletion of JAK2 produces a distinct phenotype of severe LV dysfunction associated with hypertrophy and significant mortality.These findings may offer a basis for identifying a role for JAK2 in cardiac pathology, particularly heart failure.
A controlled trial of the effect of topical glyceryl trinitrate on skin blood flow and skin elasticity in scleroderma.
Authors: A L Herrick, R J Gush, M Tully, M I Jayson
Journal: Annals of the Rheumatic Diseases (1994)

A controlled trial of the effect of topical glyceryl trinitrate on skin blood flow and skin elasticity in scleroderma
Clinical characteristics of hereditary hemochromatosis patients who lack the C282Y mutation
Authors: Nicholas J. Shaheen, Bruce R. Bacon, Ian S. Grimm
Journal: Hepatology (1998)

Approximately 85% of patients with typical hereditary hemochromatosis (HH) are homozygous for the C282Y mutation (C282Y/C282Y) in the recently identified candidate gene for HH. However, some HH patients are instead homozygous for the wild-type allele (wt/wt) at this locus. These wt/wt patients may represent a phenotypically similar, but genotypically different, heritable trait, or may be unrecognized cases of secondary iron overload. The purpose of this study is to provide an in-depth analysis of the wt/wt HH patients identified in the original description of the HH gene, and to compare them with 62 patients from the same analysis who were homozygous for the C282Y mutation. Eighteen of the 21 wt/wt HH patients from the original study were assessed for 14 historical and laboratory variables, including previously unrecognized causes of secondary iron overload, the heritability of iron overload and liver disease, and other clinical characteristics. Ten of these 18 wt/wt HH patients (55.6%) were found to have previously unrecognized causes for secondary iron overload compared with 3 of 62 (4.8%) of the C282Y/C282Y patients ( P &lt; .001). The remaining 8 wt/wt patients had no recognizable etiology of secondary iron overload. None of the 18 wt/wt patients had a family history of iron overload or liver disease, compared with 58% of the C282Y/C282Y patients ( P &lt; .001). When compared with C282Y homozygotes, the 8 wt/wt patients without secondary iron overload had a higher presenting hepatic iron index (HII) (9.5 vs. 4.7; P = .01). We conclude that, in this series of patients, over half of the wt/wt HH patients possessed previously unrecognized causes of secondary iron overload, and therefore, may have been misdiagnoses. If these cases are excluded, the number of false-negative tests is decreased, and the sensitivity of the mutational analysis is increased. However, there is a subgroup of wt/wt patients who have typical hemochromatosis without an identifiable cause of secondary iron overload. These patients may have more severe iron loading than C282Y homozygotes.
Expression of Human Organic Cation Transporter 3 in Kidney Carcinoma Cell Lines Increases Chemosensitivity to Melphalan, Irinotecan, and Vincristine
Authors: Volodymyr Shnitsar, Ronny Eckardt, Shivangi Gupta, Julia Grottker, Gerhard A. Müller, Hermann Koepsell, Gerhard Burckhardt, Yohannes Hagos
Journal: Cancer Research (2009)

Renal cell carcinoma (RCC) is usually chemoresistant. This chemoresistance could be overcome if specific cytostatics are applied for which the RCC expresses an uptake transporter. In the present study, we investigated the expression of solute carrier (SLC) transporters in different RCC lines and their ability to interact with chemotherapeutics. We tested five RCC lines for the expression of different SLCs by reverse transcription-PCR and TaqMan real-time PCR. In two of five RCC lines, A498 and 7860, we observed a highly significant expression of SLC22A3 (hOCT3). Uptake of the organic cation [(3)H]MPP (4-methyl-pyridinium iodide) into these cells and also into hOCT3 stably transfected Chinese hamster ovary (CHO) cells was inhibited by irinotecan, vincristine, and melphalan. The K(i) values [determined from Dixon plots] for irinotecan, vincristine, and melphalan were 1.72 +/- 0.45 micromol/L, 17 +/- 4.81 micromol/L, and 366 +/- 51 micromol/L, respectively. Cytotoxic activities of the selected drugs were tested by [(3)H]thymidine incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays on CHO-hOCT3, A498 (high expression of hOCT3), and ACHN cell lines (low expression of hOCT3). The growth of CHO-hOCT3 was inhibited by 20% more with irinotecan and by 50% more with vincristine compared with nontransfected CHO cells. Melphalan produced 20% to 30% more inhibition in hOCT3-expressing cells compared with nonexpressing control cells. Similar results were obtained for A498 and ACHN cells. Thus, our data support the hypothesis that the sensitivity of tumor cells to chemotherapeutic treatment depends on the expression of transporter proteins mediating specific drug accumulation into target cells.
Novel markers of normal and neoplastic human plasmacytoid dendritic cells
Authors: Teresa Marafioti, Jennifer C. Paterson, Erica Ballabio, Kaaren K. Reichard, Sara Tedoldi, Kevin Hollowood, Michael Dictor, Martin-Leo Hansmann, Stefano A. Pileri, Martin J. Dyer, Silvano Sozzani, Ivan Dikic, Andrey S. Shaw, Tony Petrella, Harald Stein, Peter G. Isaacson, Fabio Facchetti, David Y. Mason
Journal: Blood (2008)
The genome sequence of the orchid Phalaenopsis equestris
Authors: Jing Cai, Xin Liu, Kevin Vanneste, Sebastian Proost, Wen-Chieh Tsai, Ke-Wei Liu, Li-Jun Chen, Ying He, Qing Xu, Chao Bian, Zhijun Zheng, Fengming Sun, Weiqing Liu, Yu-Yun Hsiao, Zhao-Jun Pan, Chia-Chi Hsu, Ya-Ping Yang, Yi-Chin Hsu, Yu-Chen Chuang, Anne Dievart, Jean-Francois Dufayard, Xun Xu, Jun-Yi Wang, Jun Wang, Xin-Ju Xiao, Xue-Min Zhao, Rong Du, Guo-Qiang Zhang, Meina Wang, Yong-Yu Su, Gao-Chang Xie, Guo-Hui Liu, Li-Qiang Li, Lai-Qiang Huang, Yi-Bo Luo, Hong-Hwa Chen, Yves Van de Peer, Zhong-Jian Liu
Journal: Nature Genetics (2014)

Zhong-Jian Liu, Lai-Qiang Huang, Yi-Bo Luo, Hong-Hwa Chen and Yves Van de Peer report the first genome sequence of a crassulacean acid metabolism (CAM) plant, the orchid Phalaenopsis equestris. They identify genes encoding CAM pathway enzymes and find that gene duplication was likely a key process in the evolution of CAM photosynthesis. Orchidaceae, renowned for its spectacular flowers and other reproductive and ecological adaptations, is one of the most diverse plant families. Here we present the genome sequence of the tropical epiphytic orchid Phalaenopsis equestris, a frequently used parent species for orchid breeding. P. equestris is the first plant with crassulacean acid metabolism (CAM) for which the genome has been sequenced. Our assembled genome contains 29,431 predicted protein-coding genes. We find that contigs likely to be underassembled, owing to heterozygosity, are enriched for genes that might be involved in self-incompatibility pathways. We find evidence for an orchid-specific paleopolyploidy event that preceded the radiation of most orchid clades, and our results suggest that gene duplication might have contributed to the evolution of CAM photosynthesis in P. equestris. Finally, we find expanded and diversified families of MADS-box C/D-class, B-class AP3 and AGL6-class genes, which might contribute to the highly specialized morphology of orchid flowers.
Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure
Authors: Hester M. Den Ruijter, Géza Berecki, Arie O. Verkerk, Diane Bakker, Antonius Baartscheer, Cees A. Schumacher, Charly N.W. Belterman, Nicolaas de Jonge, Jan W.T. Fiolet, Ingeborg A. Brouwer, Ruben Coronel
Journal: Circulation (2008)

Fish oil reduces sudden death in patients with prior myocardial infarction. Sudden death in heart failure may be due to triggered activity based on disturbed calcium handling. We hypothesized that superfusion with omega3-polyunsaturated fatty acids (omega3-PUFAs) from fish inhibits triggered activity in heart failure.Ventricular myocytes were isolated from explanted hearts of rabbits with volume- and pressure-overload-induced heart failure and of patients with end-stage heart failure. Membrane potentials (patch-clamp technique) and intracellular calcium (indo-1 fluorescence) were recorded after 5 minutes of superfusion with Tyrode's solution (control), omega-9 monounsaturated fatty acid oleic acid (20 micromol/L), or omega3-PUFAs (docosahexaenoic acid or eicosapentaenoic acid 20 micromol/L). omega3-PUFAs shortened the action potential at low stimulation frequencies and caused an approximately 25% decrease in diastolic and systolic calcium (all P<0.05). Subsequently, noradrenalin and rapid pacing were used to evoke triggered activity, delayed afterdepolarizations, and calcium aftertransients. omega3-PUFAs abolished triggered activity and reduced the number of delayed afterdepolarizations and calcium aftertransients compared with control and oleic acid. Omega3-PUFAs reduced action potential shortening and intracellular calcium elevation in response to noradrenalin. Results from human myocytes were in accordance with the findings obtained in rabbit myocytes.Superfusion with omega3-PUFAs from fish inhibits triggered arrhythmias in myocytes from rabbits and patients with heart failure by lowering intracellular calcium and reducing the response to noradrenalin.
Hemodynamic effects of PEEP
Authors: A. Kotanidou, S. Zakynthinos, A. Armaganidis, D. Sfiras, M. Pitaridis, J. Floros, C. Roussos, A. Mercat, J. L. Teboul, R. Boujdaria, L. Graini, O. Pinamonti, F. Lenique, J. Depret, Ch. Richard, G. Conti, F. Baigorri, A. De Monte, U. Blanch, R. Fernàndez, J. Valles, A. Artigas, L. Blanch, T. Imai, N. Fukura, T. Nara, T. Fujita, R. Giuliani, V. M. Ranieri, M. Dambrosio, N. Brienza, G. Cinnella, A. Brienza
Journal: Intensive Care Medicine (1992)
Abstract 3639: Cell death mechanisms associated with the carbamoylating activity of the anticancer prodrug Laromustine
Authors: Adam N. Paine, V. Alexandra Praggastis, Lindsay E. Dale, Jared L. Tepper, Bridget Reichelderfer, Kevin P. Rice
Journal: Cancer Research (2010)

Abstract The preclinical anticancer prodrug Laromustine (VNP40101M; Cloretazine) yields 2-chloroethylating and methyl carbamoylating activities upon activation in cells. While the induction of DNA damage from its chloroethylating activity is widely considered to be the primary cause of its therapeutic cytotoxicity, Laromustine's carbamoylating activity has proven critical to the drug's mechanistic profile. Methyl isocyanate, the carbamoylating species derived from Laromustine in situ, can enhance the effectiveness of DNA damaging agents, including the cogenerated chloroethylating agent. This consequence is thought to be a result of a diminishment of cellular DNA damage response. However, carbamoylating agents themselves cause acute cell death in cultured mammalian neoplastic cells, principally via apoptosis. Several overlapping cell death pathways can be induced upon exposure to Laromustine's carbamoylating activity. Using Laromustine and its analogs, the chloroethylating-only 90CE and the carbamoylating-only 101MDCE, we identified molecular markers of apoptosis via Western blot analysis and flow cytometry. Poly(ADP-ribose) polymerase (PARP) is often proteolyzed by caspase-3 in the course of an apoptotic death. We report here that Laromustine, with its carbamoylating activity, induced PARP cleavage similarly to the cytotoxic agent etoposide in HL-60 human leukemia cells. In addition, flow cytometry analyses using FITC-annexin V / propidium iodide staining revealed that the carbamoylating activity of Laromustine is responsible for substantial apoptosis in HL-60 cells at clinically relevant doses within three hours of drug treatment. However, the DNA damaging, 2-chloroethylating activity did not induce appreciable apoptosis in similar experiments. Levels of poly(ADP-ribosyl)ation and expression levels of the Bax and Bcl-2 proteins are also being investigated. Given its effects on DNA repair systems and its provocation of apoptosis, methyl isocyanate continues to demonstrate its utility to the cytotoxic action of Laromustine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3639.
A POMC variant implicates β-melanocyte-stimulating hormone in the control of human energy balance
Authors: Yung Seng Lee, Ben G. Challis, Darren A. Thompson, Giles S.H. Yeo, Julia M. Keogh, Michael E. Madonna, Vicki Wraight, Matthew Sims, Vincent Vatin, David Meyre, Julian Shield, Christine Burren, Zala Ibrahim, Tim Cheetham, Peter Swift, Anthea Blackwood, Chiao-Chien Connie Hung, Nicholas J. Wareham, Philippe Froguel, Glenn L. Millhauser, Stephen O'Rahilly, I. Sadaf Farooqi
Journal: Cell Metabolism (2006)
Recommendations for standardization and specifications in automated electrocardiography: bandwidth and digital signal processing. A report for health professionals by an ad hoc writing group of the Committee on Electrocardiography and Cardiac Electrophysiology of the Council on Clinical Cardiology, American Heart Association.
Authors: J J Bailey, A S Berson, A Garson, L G Horan, P W Macfarlane, D W Mortara, C Zywietz
Journal: Circulation (1990)
Incidence of Chronic Paronychia
Authors: Orville J. Stone
Journal: JAMA (1963)

IT IS GENERALLY agreed among dermatologists that chronic paronychia seems to be more common among diabetics. However, prior to this study the actual incidence of chronic paronychia in diabetics or in a general medical population had never been determined. This incidence study has been part of multiple studies to increase our knowledge of chronic paronychia.  Clinical Diagnosis  Chronic paronychia is entirely a clinical diagnosis, but the picture presented is so characteristic as to present no diagnostic difficulties. Paronychia, by definition, is an inflammation of the tissue surrounding the nail plate. Acute and chronic paronychia differ by more than the duration that they have been present. Acute paronychia is similar to an acute cellulitis at any other site and usually it is of streptococcic or staphylococcic origin. It does not need further discussion here except to state that only rarely would such a lesion be followed by a chronic paronychia. Chronic
PERMANENT ENLARGEMENT OF THE LIPS AND FACE
Authors: William Allen Pusey
Journal: JAMA (1933)

To the Editor:  —Some comments seem to be needed on the paper Permanent Enlargement of the Lips and Face Secondary to Recurring Swellings and Associated with Facial Paralysis: A Clinical Entity, by New and Kirch (The Journal, April 22, p. 1230).  authors say that The condition is apparently a clinical entity, but we have been able to find only slight mention of it in the literature.   condition is a clinical entity which has been recognized for fifty years and repeatedly described. It was first described by Jonathan Hutchinson in the Medical Times and Gazette ( 1 :4, 1883). It was again considered by him in the Illustrated Medical News (Oct. 20, 1888, p. 82) and in the Archives of Surgery , London ( 4 , plate LXVI, 1893). It has also been described by Weaver and Tunnicliffe ( J. Infec. Dis.  5 :569 [Dec. 18] 1908), by Bourgeois and Egger ( Rev. hebd. , May
Anticoagulation before Cardioversion for Atrial Fibrillation
Authors: Michael B. Jacobs
Journal: Annals of Internal Medicine (1992)

Letters15 April 1992Anticoagulation before Cardioversion for Atrial FibrillationMichael B. Jacobs, MDMichael B. Jacobs, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-116-8-698_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:The article addressing the question of which subgroups of patients with atrial fibrillation need anticoagulation by Albers and colleagues (1) is a welcome addition to the medical literature. However, the implied advice about managing patients with paroxysmal atrial fibrillation may be misleading. Atwood (2) states that, "Unlike patients with chronic atrial fibrillation, patients with acute atrial fibrillation of less than 3 days duration do not require anticoagulant therapy before cardioversion." (Here, I equate each new paroxysm of atrial fibrillation with "acute atrial fibrillation.") In support of this statement, he cites an article by Bjerkelund and Orning (3);...References1. AlbersAtwoodHirshShermanHughesConnolly GJJDRS. Stroke prevention in nonvalvular atrial fibrillation. Ann Intern Med. 1991;115:727-36. LinkGoogle Scholar2. Atwood J. Cause, evaluation, and management of atrial fibrillation. In: Albers GW, moderator. Stroke prevention in nonvalvular atrial fibrillation. Ann Intern Med. 1991;115:727-36. Google Scholar3. BjerkelandOrning CO. The efficacy of anticoagulant therapy in preventing embolism related to d.c. electrical conversion of atrial fibrillation. Am T Cardiol. 1969;23:208-16. CrossrefMedlineGoogle Scholar1. AlbersAtwoodHirshShermanHughesConnolly GJJDRS. Stroke prevention in nonvalvular atrial fibrillation. Ann Intern Med. 1991;115:727-36. LinkGoogle Scholar2. . Predictors of thromboembolism in atrial fibrillation: I. clinical features of patients at risk. Ann Intern Med. 1992;116:1-5. LinkGoogle Scholar3. DunnAlexanderde SilvaHildner MJRF. Antithrombotic therapy in atrial fibrillation. Chest. 1989;95:118S-25S. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Stanford University Clinic Stanford, CA 94305 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byElektrische Therapie von Vorhofflimmern und Vorhofflattern 15 April 1992Volume 116, Issue 8Page: 698-699KeywordsAnticoagulant therapyAtrial fibrillation Issue Published: 15 April 1992 PDF downloadLoading ...
Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs
Authors: Jan Florian Heuer, Paolo Pelosi, Peter Hermann, Christina Perske, Thomas A. Crozier, Wolfgang Brück, Michael Quintel
Journal: Intensive Care Medicine (2011)

To determine reciprocal and synergistic effects of acute intracranial hypertension and ARDS on neuronal and pulmonary damage and to define possible mechanisms.Twenty-eight mechanically ventilated pigs were randomized to four groups of seven each: control; acute intracranial hypertension (AICH); acute respiratory distress syndrome (ARDS); acute respiratory distress syndrome in combination with acute intracranial hypertension (ARDS + AICH). AICH was induced with an intracranial balloon catheter and the inflation volume was adjusted to keep intracranial pressure (ICP) at 30-40 cmH2O. ARDS was induced by oleic acid infusion. Respiratory function, hemodynamics, extravascular lung water index (ELWI), lung and brain computed tomography (CT) scans, as well as inflammatory mediators, S100B, and neuronal serum enolase (NSE) were measured over a 4-h period. Lung and brain tissue were collected and examined at the end of the experiment.In both healthy and injured lungs, AICH caused increases in NSE and TNF-alpha plasma concentrations, extravascular lung water, and lung density in CT, the extent of poorly aerated (dystelectatic) and atelectatic lung regions, and an increase in the brain tissue water content. ARDS and AICH in combination induced damage in the hippocampus and decreased density in brain CT.AICH induces lung injury and also exacerbates pre-existing damage. Increased extravascular lung water is an early marker. ARDS has a detrimental effect on the brain and acts synergistically with intracranial hypertension to cause histological hippocampal damage.
439 HEPATITIS C CO-INFECTION SENSITIZES CD4+ T CELLS TOWARDS FAS-INDUCED APOPTOSIS IN HIV-POSITIVE PATIENTS
Authors: C. Körner, F. Tolksdorf, D. Schulte, B. Krämer, M. Coenen, A. Glässner, M. Eisenhardt, T. Sauerbruch, J. Nattermann, J. Rockstroh, U. Spengler
Journal: Journal of Hepatology (2010)