tbuckley/cabot-search huggingface dataset:
Sequential follow up observations of a patient with rubella associated persistent arthritis.
Authors: D K Ford, G D Reid, A J Tingle, L A Mitchell, M Schulzer
Journal: Annals of the Rheumatic Diseases (1992)

In 1985 a patient was described whose persistent polyarthritis was found to be aetiologically linked to rubella virus infection through the detection of repeated maximal synovial lymphocyte proliferative responses to rubella virus antigen and by isolation of rubella virus from her synovium. Follow up over the succeeding seven years has shown continuing chronic polyarthritis and persistent synovial lymphocyte responses to rubella virus antigen with the additional observation that she has a defective humoral immune response against rubella virus.
A Bioinformatics Approach Identifies Signal Transducer and Activator of Transcription-3 and Checkpoint Kinase 1 as Upstream Regulators of Kidney Injury Molecule-1 after Kidney Injury
Authors: Amrendra Kumar Ajay, Tae-Min Kim, Victoria Ramirez-Gonzalez, Peter J. Park, David A. Frank, Vishal S. Vaidya
Journal: Journal of the American Society of Nephrology (2013)

Kidney injury molecule-1 (KIM-1)/T cell Ig and mucin domain-containing protein-1 (TIM-1) is upregulated more than other proteins after AKI, and it is highly expressed in renal damage of various etiologies. In this capacity, KIM-1/TIM-1 acts as a phosphatidylserine receptor on the surface of injured proximal tubular epithelial cells, mediating phagocytosis of apoptotic cells, and it may also act as a costimulatory molecule for immune cells. Despite recognition of KIM-1 as an important therapeutic target for kidney disease, the regulators of KIM-1 transcription in the kidney remain unknown. Using a bioinformatics approach, we identified upstream regulators of KIM-1 after AKI. In response to tubular injury in rat and human kidneys or oxidant stress in human proximal tubular epithelial cells (HPTECs), KIM-1 expression increased significantly in a manner that corresponded temporally and regionally with increased phosphorylation of checkpoint kinase 1 (Chk1) and STAT3. Both ischemic and oxidant stress resulted in a dramatic increase in reactive oxygen species that phosphorylated and activated Chk1, which subsequently bound to STAT3, phosphorylating it at S727. Furthermore, STAT3 bound to the KIM-1 promoter after ischemic and oxidant stress, and pharmacological or genetic induction of STAT3 in HPTECs increased KIM-1 mRNA and protein levels. Conversely, inhibition of STAT3 using siRNAs or dominant negative mutants reduced KIM-1 expression in a kidney cancer cell line (769-P) that expresses high basal levels of KIM-1. These observations highlight Chk1 and STAT3 as critical upstream regulators of KIM-1 expression after AKI and may suggest novel approaches for therapeutic intervention.
Etanercept Treatment for Children and Adolescents with Plaque Psoriasis
Authors: Amy S. Paller, Elaine C. Siegfried, Richard G. Langley, Alice B. Gottlieb, David Pariser, Ian Landells, Adelaide A. Hebert, Lawrence F. Eichenfield, Vaishali Patel, Kara Creamer, Angelika Jahreis
Journal: New England Journal of Medicine (2008)

Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis.
Viruses and hepatocellular carcinoma.
Authors: S Sherlock
Journal: Gut (1994)

Viruses and hepatocellular carcinoma S SherlockBoth hepatitis B virus (HBV) and hepatitis C virus (HCV) are important worldwide prob- lems.It is believed that 300 million people have been exposed to hepatitis B.' In Europe, based on a carrier rate in blood donors of 0 O/% and a population of 400 million, it is estimated that four million have been exposed to hepatitis C. Hepatocellular cancer is estimated to have an incidence of between 250 000 and 1-2 million per year worldwide.2It is the seventh commonest cause of cancer in men, and most show evidence of HBV or HCV infection.The relation of the virus to the development of hepatocellular carcinoma (HCC) is through chronic hepatitis and cirrhosis (Fig 1).Almost all patients with virus related HCC have an underlying cirrhosis.The hepatocyte necrosis and mitosis of chronic hepatitis favour nodular regeneration which, in appropriate circum- stances, is followed by hepatocyte dysplasia and carcinoma.3Although nodular regenera- tion and cirrhosis remain the most important antecedents, the tumour can develop in the absence of cirrhosis.In this case, and by analogy with the HBV-like woodchuck chronic hepatitis, necroinflammatory activity may be an important requisite.
Role of Dynamin-Related Protein 1 (Drp1)-Mediated Mitochondrial Fission in Oxygen Sensing and Constriction of the Ductus Arteriosus
Authors: Zhigang Hong, Shelby Kutty, Peter T. Toth, Glenn Marsboom, James M. Hammel, Carolyn Chamberlain, John J. Ryan, Hannah J. Zhang, Willard W. Sharp, Erik Morrow, Kalyani Trivedi, E. Kenneth Weir, Stephen L. Archer
Journal: Circulation Research (2013)

Rationale: Closure of the ductus arteriosus (DA) is essential for the transition from fetal to neonatal patterns of circulation. Initial P O 2 -dependent vasoconstriction causes functional DA closure within minutes. Within days a fibrogenic, proliferative mechanism causes anatomic closure. Though modulated by endothelial-derived vasodilators and constrictors, O 2 sensing is intrinsic to ductal smooth muscle cells and oxygen-induced DA constriction persists in the absence of endothelium, endothelin, and cyclooxygenase mediators. O 2 increases mitochondrial-derived H 2 O 2 , which constricts ductal smooth muscle cells by raising intracellular calcium and activating rho kinase. However, the mechanism by which oxygen changes mitochondrial function is unknown. Objective: The purpose of this study was to determine whether mitochondrial fission is crucial for O 2 -induced DA constriction and closure. Methods and Results: Using DA harvested from 30 term infants during correction of congenital heart disease, as well as DA from term rabbits, we demonstrate that mitochondrial fission is crucial for O 2 -induced constriction and closure. O 2 rapidly (&lt;5 minutes) causes mitochondrial fission by a cyclin-dependent kinase- mediated phosphorylation of dynamin-related protein 1 (Drp1) at serine 616. Fission triggers a metabolic shift in the ductal smooth muscle cells that activates pyruvate dehydrogenase and increases mitochondrial H 2 O 2 production. Subsequently, fission increases complex I activity. Mitochondrial-targeted catalase overexpression eliminates P O 2 -induced increases in mitochondrial-derived H 2 O 2 and cytosolic calcium. The small molecule Drp1 inhibitor, Mdivi-1, and siDRP1 yield concordant results, inhibiting O 2 -induced constriction (without altering the response to phenylephrine or KCl) and preventing O 2 -induced increases in oxidative metabolism, cytosolic calcium, and ductal smooth muscle cells proliferation. Prolonged Drp1 inhibition reduces DA closure in a tissue culture model. Conclusions: Mitochondrial fission is an obligatory, early step in mammalian O 2 sensing and offers a promising target for modulating DA patency.
An Assessment of Intratumor Phagocytic and Surface Marker-Bearing Cells in a Series of Autochthonous and Early Passaged Chemically Induced Murine Sarcomas2
Authors: H. F. Pross, R. S. Kerbel
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article An Assessment of Intratumor Phagocytic and Surface Marker-Bearing Cells in a Series of Autochthonous and Early Passaged Chemically Induced Murine Sarcomas Get access H. F. Pross, H. F. Pross Search for other works by this author on: Oxford Academic PubMed Google Scholar R. S. Kerbel R. S. Kerbel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 5, November 1976, Pages 1157–1167, https://doi.org/10.1093/jnci/57.5.1157 Published: 01 November 1976 Article history Received: 19 January 1976 Accepted: 16 April 1976 Published: 01 November 1976
Long-term improvement in mdx cardiomyopathy after therapy with peptide-conjugated morpholino oligomers†
Authors: Natee Jearawiriyapaisarn, Hong M. Moulton, Peter Sazani, Ryszard Kole, Monte S. Willis
Journal: Cardiovascular Research (2009)

The cardiomyopathy found in Duchenne muscular dystrophy (DMD) is responsible for death due to heart failure in ∼30% of patients and additionally contributes to many DMD morbidities. Strategies to bypass DMD-causing mutations to allow an increase in body-wide dystrophin have proved promising, but increasing cardiac dystrophin continues to be challenging. The purpose of this study was to determine if therapeutic restoration of cardiac dystrophin improved the significant cardiac hypertrophy and diastolic dysfunction identified in X-linked muscular dystrophy (mdx) dystrophin-null mouse due to a truncation mutation over time after treatment. Mice lacking dystrophin due to a truncation mutation (mdx) were given an arginine-rich, cell-penetrating, peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) that delivered a splice-switching oligonucleotide-mediated exon skipping therapy to restore dystrophin in mdx mice before the development of detectable cardiomyopathy. PPMO successfully restored cardiac dystrophin expression, preserved cardiac sarcolemma integrity, and prevented the development of cardiac pathology that develops in mdx-null mice over time. By echocardiography and Doppler analysis of the mitral valve, we identified that PPMO treatment of mdx mice prevented the cardiac hypertrophy and diastolic dysfunction identified in sham-treated, age-matched mdx mice, characteristic of DMD patients early in the disease process, in as little as 5–6 weeks after the initiation of treatment. Surprisingly, despite the short-term replacement of cardiac dystrophin (<1% present after 12 weeks by immunodetection), PPMO therapy also provided a durable cardiac improvement in cardiac hypertrophy and diastolic dysfunction for up to 7 months after the initiation of treatment. These results demonstrate for the first time that PPMO-mediated exon skipping therapy early in the course of DMD may effectively prevent or slow down associated cardiac hypertrophy and diastolic dysfunction with significant long-term impact.
Eccentric training for prevention of hamstring injuries may depend on intervention compliance: a systematic review and meta-analysis
Authors: Adam P Goode, Michael P Reiman, Lloyd Harris, Lucia DeLisa, Aaron Kauffman, David Beltramo, Charles Poole, Leila Ledbetter, Andrea B Taylor
Journal: British Journal of Sports Medicine (2014)

Background Hamstring injury is a prevalent muscle injury in sports. Inconclusive evidence exists for eccentric hamstring strengthening to prevent hamstring injuries. One reason for this discrepancy may be the influence intervention non-compliance has on individual study estimates, and therefore pooled estimates. Objective This systematic review aims to determine the effect of eccentric hamstring strengthening on the risk of hamstring injury and quantitatively explores the impact of intervention non-compliance on the precision, heterogeneity and strength of pooled estimates. Methods A computer-assisted literature search of Medline, CINAHL, Cochrane, EMBASE, AMED, SportDiscus and PEDro databases was conducted with keywords related to eccentric strengthening and hamstring injury. The search was conducted from the end of a previous comprehensive review forward (1 December 2008 to 31 December 2013). Random-effects models were used for both main effects and a sensitivity analysis. Pooled estimate precision was measured with a confidence limit ratio (confidence limit ratio (CLR); upper limit divided by the lower limit) and heterogeneity was assessed with I 2 , Cochrane's-Q and τ 2 . A protocol was not registered for this review. Results Four out of 349 studies met the inclusion criteria. In main effects analysis, eccentric hamstring training did not reduce the risk of hamstring injury (risk ratio [RR]=0.59 ((95% CI 0.24 to 1.44)). This estimate was imprecise (CLR=6.0) with significant heterogeneity (p value 0.02, 69.6% variation and t 2 =0.57). Subjects compliant with eccentric strengthening had a significant (RR=0.35 ((95% CI 0.23 to 0.55)) reduction in hamstring injuries. This estimate was precise (CLR=2.4) and homogenous (p value=0.38, 2.8% variation and t 2 =0.007). Conclusions The null-biased effect in using intent-to-treat methods from intervention non-compliance has a substantial impact on the precision, heterogeneity and the direction and strength of pooled estimates. Eccentric strengthening, with good compliance, appears to be successful in prevention of hamstring injury.
Antiapoptotic effect of ectopic TAL1/SCL expression in a human leukemic T-cell line.
Authors: M Bernard, E Delabesse, S Novault, O Hermine, E A Macintyre
Journal: Cancer Research (1998)

Aberrant expression of TAL1 occurs frequently in human T-cell acute lymphoblastic leukemia. The effect of TAL1 expression in the T-cell lymphoid precursor, however, remains unclear. In the current study, we have developed TAL1 stable transfectants in a human immature T-cell lymphoid cell line. Whereas no effect on proliferation, cell culture density, or cell cycle was detected, the transfectants were more resistant than the parental cell line to apoptosis induced by chemotherapeutic agents including etoposide, daunorubicin, doxorubicin, cytosine arabinoside, methotrexate and vincristine and also to apoptosis induced by Fas/CD95 cross-linking. This effect was independent of the cytostatic effects of the drugs. The basic domain-deleted transfectants did not demonstrate altered sensitivity, suggesting that DNA binding was necessary for resistance to apoptosis. The ability to alter the response to a wide range of cell death-inducing stimuli suggests that TAL1 acts at a late stage of the apoptotic cascade. These data therefore provide direct evidence of an antiapoptotic effect of ectopic TAL1 expression in response to cytotoxic agents, thus providing insight into its oncogenic function in T-cell acute lymphoblastic leukemia and a novel experimental model to further investigate the underlying mechanisms. These data also have potential practical significance for cytotoxic therapy of this disorder.
Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial
Authors: Alice Gottlieb, Alan Menter, Alan Mendelsohn, Yaung-Kaung Shen, Shu Li, Cynthia Guzzo, Scott Fretzin, Rod Kunynetz, Arthur Kavanaugh
Journal: The Lancet (2009)
WHAT HAPPENS TO ALCOHOLICS
Authors: FREDERICK LEMERE
Journal: American Journal of Psychiatry (1953)

1. Approximately 28% of all alcoholics will drink themselves to death, 7% will regain partial control of their drinking, 3% will be able to drink moderately again, and 29% will continue to have the problem of drinking throughout their lifetime. Twenty-two percent will stop drinking during a terminal illness and 11% So will quit drinking exclusive of a terminal illness. 2. Most alcoholics who quit drinking will probably do so on their own without outside help (7% of this series of 500 cases). Spiritual reconversion has been the biggest help to alcoholics who have become abstinent (3% of this series). In the past medical treatment has been of some, but not great, help (1% So of this series). 3. The average life expectancy of these 5oo alcoholics was 52 years. Many alcoholics quit for prolonged periods of time only to relapse at some later date.
A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression: implications for the pathogenesis
Authors: V. M. Vazgiourakis, M. I. Zervou, C. Choulaki, G. Bertsias, M. Melissourgaki, N. Yilmaz, P. Sidiropoulos, D. Plant, L. A. Trouw, R. E. Toes, D. Kardassis, S. Yavuz, D. T. Boumpas, G. N. Goulielmos
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> In systemic lupus erythematosus (SLE) sustained CD40L expression by T cells and platelets activates a variety of cells via its receptor CD40 contributing to disease pathogenesis. Although CD40 has recently been identified in genome-wide association study as a novel rheumatoid arthritis susceptibility gene such an association has not been documented for SLE. <h3>Objective</h3> To investigate whether the rs4810485 <i>CD40</i> single nucleotide polymorphism (SNP) is associated with increased risk for SLE and its impact on <i>CD40</i> expression. <h3>Materials and methods</h3> The primary sample set consisted of 351 patients with SLE and 670 matched healthy controls of Greek origin. 158 patients with SLE and 155 controls from Turkey were used as a replication sample. Genotyping of rs4810485 was performed by restriction fragment length polymorphism and the Sequenom MassArray technology. The expression of <i>CD40</i> mRNA and protein was assessed in unstimulated and lipopolysaccharide-stimulated peripheral blood mononuclear cells by quantitative real time PCR and flow cytometry, respectively. <h3>Results</h3> The minor allele T of <i>CD40</i> rs4810485 SNP was significantly under-represented in Greek patients with SLE compared with healthy controls (OR=0.65, 95% CI 0.54 to 0.79). The association was replicated in the Turkish cohort (OR=0.57, 95% CI 0.41 to 0.80; meta-analysis of 509 patients with SLE and 825 healthy controls: OR=0.63, 95% CI 0.53 to 0.74, p = 2×10<sup>−8</sup>). In both cases and controls, the rs4810485 G/T and T/T genotypes were associated with significantly reduced <i>CD40</i> mRNA and protein expression in peripheral blood CD14+ monocytes and CD19+ B cells compared with G/G genotype, both under basal conditions and following stimulation. <h3>Conclusions</h3> <i>CD40</i> has been identified as a new susceptibility locus in Greek and Turkish patients with SLE. The rs4810485 minor allele T is under-represented in SLE and correlates with reduced <i>CD40</i> expression in peripheral blood monocytes and B cells, with potential implications for the regulation of aberrant immune responses in the disease.
Myozap, a Novel Intercalated Disc Protein, Activates Serum Response Factor–Dependent Signaling and Is Required to Maintain Cardiac Function In Vivo
Authors: Thalia S. Seeger, Derk Frank, Claudia Rohr, Rainer Will, Steffen Just, Christine Grund, Robert Lyon, Mark Luedde, Manfred Koegl, Farah Sheikh, Wolfgang Rottbauer, Werner W. Franke, Hugo A. Katus, Eric N. Olson, Norbert Frey
Journal: Circulation Research (2010)

The intercalated disc (ID) is a highly specialized cell-cell contact structure that ensures mechanical and electric coupling of contracting cardiomyocytes. Recently, the ID has been recognized to be a hot spot of cardiac disease, in particular inherited cardiomyopathy.Given its complex structure and function we hypothesized that important molecular constituents of the ID still remain unknown.Using a bioinformatics screen, we discovered and cloned a previously uncharacterized 54 kDa cardiac protein which we termed Myozap (Myocardium-enriched zonula occludens-1-associated protein). Myozap is strongly expressed in the heart and lung. In cardiac tissue it localized to the ID and directly binds to desmoplakin and zonula occludens-1. In a yeast 2-hybrid screen for additional binding partners of Myozap we identified myosin phosphatase-RhoA interacting protein (MRIP), a negative regulator of Rho activity. Myozap, in turn, strongly activates SRF-dependent transcription through its ERM (Ezrin/radixin/moesin)-like domain in a Rho-dependent fashion. Finally, in vivo knockdown of the Myozap ortholog in zebrafish led to severe contractile dysfunction and cardiomyopathy.Taken together, these findings reveal Myozap as a previously unrecognized component of a Rho-dependent signaling pathway that links the intercalated disc to cardiac gene regulation. Moreover, its subcellular localization and the observation of a severe cardiac phenotype in zebrafish, implicate Myozap in the pathogenesis of cardiomyopathy.
Advances in Immuno–Positron Emission Tomography: Antibodies for Molecular Imaging in Oncology
Authors: Scott M. Knowles, Anna M. Wu
Journal: Journal of Clinical Oncology (2012)

Identification of cancer cell–surface biomarkers and advances in antibody engineering have led to a sharp increase in the development of therapeutic antibodies. These same advances have led to a new generation of radiolabeled antibodies and antibody fragments that can be used as cancer-specific imaging agents, allowing quantitative imaging of cell-surface protein expression in vivo. Immuno–positron emission tomography (immunoPET) imaging with intact antibodies has shown success clinically in diagnosing and staging cancer. Engineered antibody fragments, such as diabodies, minibodies, and single-chain Fv (scFv) –Fc, have been successfully employed for immunoPET imaging of cancer cell–surface biomarkers in preclinical models and are poised to bring same-day imaging into clinical development. ImmunoPET can potentially provide a noninvasive approach for obtaining target-specific information useful for titrating doses for radioimmunotherapy, for patient risk stratification and selection of targeted therapies, for evaluating response to therapy, and for predicting adverse effects, thus contributing to the ongoing development of personalized cancer treatment.
T-Vector Direction Differentiates Postpacing From Ischemic T-Wave Inversion in Precordial Leads
Authors: Alexei Shvilkin, Kalon K.L. Ho, Michael R. Rosen, Mark E. Josephson
Journal: Circulation (2005)

Postpacing precordial T-wave inversion (TWI), known as cardiac memory (CM), mimics ischemic precordial TWI, and there are no established ECG criteria that adequately distinguish between the two. On the basis of CM properties (postpacing sinus rhythm T vector approaching the direction of the paced QRS vector), we hypothesized that CM induced by right ventricular pacing would manifest a TWI pattern different from that of precordial ischemic TWI, thereby discriminating between the two.T-wave axis, polarity, and amplitude on a 12-lead ECG during sinus rhythm were compared between CM and ischemic patients. The CM group incorporated 13 patients who were paced in DDD mode with short atrioventricular delay for 1 week after elective pacemaker implantation. The ischemic group consisted of 47 patients with precordial TWI identified among 228 consecutive patients undergoing percutaneous coronary intervention for an acute coronary syndrome. The combination of (1) positive T(aVL), (2) positive or isoelectric T(I), and (3) maximal precordial TWI>TWI(III) was 92% sensitive and 100% specific for CM, discriminating it from ischemic precordial TWI.CM induced by right ventricular pacing results in a distinctive T-vector pattern that allows discrimination from ischemic precordial T-wave inversions regardless of the coronary artery involved.