tbuckley/cabot-search huggingface dataset:
Abstract 5159: The histone methyltransferase SUV39H2 is a novel target of anticancer therapy
Authors: Kembun Sone, Yusuke Nakamura, Ryuji Hamamoto
Journal: Cancer Research (2014)

Abstract Besides genetic disorders, dysregulation of epigenetic machinery has been proved to play a crucial role in human carcinogenesis, and the histone methylation/demethylation process has been considered as one of key regulators for this event. In this study, we demonstrate that one of the HMTs, suppressor of variegation 3-9 homolog 2 (SUV39H2), plays pivotal roles in human carcinogenesis. Quantitative real-time PCR revealed that SUV39H2 is aberrantly overexpressed in lung cancer, bladder cancer and multiple myeloma compared with their corresponding normal tissues, and immunohistochemical analysis revealed its positive staining in 251 out of 392 lung cancer cases and 16 of 29 bladder cancer cases, while no significant staining was observed in various normal tissues we examined. cDNA microarray analysis using a number of clinical tissues also confirms overexpression of SUV39H2 in various types of cancer. SUV39H2-specific small interfering RNAs significantly knocked down its expression, and caused the G1 arrest as well as suppression of cancer cell growth. Since SUV39H2 expression was undetectable in the normal tissues, SUV39H2 is considered to be an ideal target for development of tumor-specific therapeutics. Citation Format: Kembun Sone, Yusuke Nakamura, Ryuji Hamamoto. The histone methyltransferase SUV39H2 is a novel target of anticancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5159. doi:10.1158/1538-7445.AM2014-5159
Assessing Liability for Health Care Entities That Insufficiently Prepare for Catastrophic Emergencies
Authors: James G. Hodge, Erin Fuse Brown
Journal: JAMA (2011)

LAWSUITS AGAINST HOSPITALS AND OTHER HEALTH CARE entities alleging liability for patient harms are brought and settled routinely in the United States. However, the settlement by health care giant Tenet Healthcare, on the eve of trial on March 23, 2011, in Preston v Tenet Healthsystem Memorial Medical Center, falls outside the norm of routine entity liability cases. The class of plaintiffs in New Orleans alleged not just that Tenet’s emergency responses at its Memorial Medical Center during Hurricane Katrina were insufficient but that Tenet’s failure to prepare for a foreseeable emergency caused their harms. Avoiding the prospect of a negative judgment at trial, Tenet’s settlement implicates the increasing potential for health care entities to incur liability for deficiencies in emergency preparedness. It may renew demands to immunize entities from liability in future emergencies and requires a reassessment of the legal standard by which hospitals and other health care entities may be judged.
DOUBLE EMBOLIC GANGRENE OF THE LOWER EXTREMITIES AS A COMPLICATION OF PNEUMONIA.
Authors: FRED F. ATTIX
Journal: JAMA (1906)

<h3>Patient.</h3> —A. J., aged 56, male, medium height, weight and figure. <h3>History.</h3> —The patient has always used alcoholic beverages in moderation. The present illness began Jan. 20, 1906. Twelve days previously, he developed what he thought to be a cold; he used domestic remedies, but was not careful to avoid needless exposure. This state of affairs lasted for ten days. On the eleventh day he sent word that he could not leave his bed and a physician was summoned. <h3>Examination.</h3> —Auscultation and the physical signs showed that there was pneumonia in the right lower lobe which was approaching resolution. The temperature was 103, pulse 160, and respiration 60. There was cyanosis and the lower extremities were cold. <h3>Consultation.</h3> —On the following day I was called in consultation. At that time there was mental apathy and moderate effort was necessary to rouse the patient who then showed mild delirium. The pupils
A Bill of Rights for Alcoholic People
Authors: Morris E. Chafetz
Journal: JAMA (1972)

Landmark events on behalf of oppressed and disadvantaged people are slow in coming and their importance may be unrecognized at the time of their occurrence. Pinel's striking of the chains from the mentally ill at Salpêtrière Prison was likely unheralded as the dawn of a new era for the mentally ill. Similarly, the far-reaching implications of the Emancipation Proclamation on racial problems in the United States were probably not fully appreciated at the time of its inception. But times, tides, and communications change and the people and the medical profession of this country can witness the dawn of a new day for alcoholic people. A Bill of Rights was promulagated for them by the Commissioners on Uniform State Laws at their annual meeting this past August. This commission, made up of legal experts from each of the 50 states appointed by their respective governors, adopted the Uniform Alcoholism and Intoxication
Abstract 5262: Resistance to fenretinide in neuroblastoma is associated with increased expression of sphingosine kinase and sphingosine-1-phosphate receptors and targeting sphingosine kinase reverses resistance
Authors: Matthew V. Ghent, Youngleem Kim, Ana Jakimenko, C Patrick Reynolds
Journal: Cancer Research (2010)

Abstract The synthetic retinoid fenretinide, N-(4-hydroxyphenyl) retinamide (4-HPR), is selectively cytotoxic to cancer cells via increases in dihydroceramide levels and generation of reactive oxygen species and has clinical activity against recurrent neuroblastoma (J Clin Oncol 27: 15s abstr 10009, 2009). Metabolism of ceramides into various sphingolipid species, including sphingosine, and phosphorylation of dihydrosphingosine and sphingosine by sphingosine kinase 1 (SPHK1) are anti-apoptotic and thought to counter cytotoxicity mediated by ceramides. Multistep selection for resistance to 4-HPR was performed with a 4-HPR sensitive neuroblastoma cell line, SMS-KCNR (IC99=4.6 uM), resulting in the 4-HPR resistant line, KCNR-FR (IC99=19.9 uM). We generated a TaqMan low-density array (TLDA) that measures expression of 42 genes involved in ceramide synthesis and metabolism by quantitative RT-PCR. Genes overexpressed in KCNR-FR relative to SMS-KCNR included ceramide desaturase 2 (14.1-fold), sphingosine-1-phosphate receptors S1PR2, 3, and 4 (2.4, 1.6, and 1.3-fold, respectively), and SPHK1 (5.2-fold). These data point toward 4-HPR resistance being mediated by sphingosine-1-phosphate or dihydrosphingosine-1-phosphate, both of which are generated via phosphorylation of sphingosine by SPHK1. SPHK1-specific RNAi knockdown decreased SPHK1 mRNA expression (36% ± 0.007 of scrambled RNAi, p&amp;lt;0.05) and significantly increased apoptosis (35.8 ± 1.7%; p&amp;lt;0.05) in KCNR-FR treated with 4-HPR relative to scrambled RNAi controls (8.8 ± 6.5%; p&amp;lt;0.05). Safingol (L-threo-dihydrosphingosine), a putative sphingosine kinase inhibitor in phase I trials, partially reversed KCNR-FR resistance to 4-HPR (Combination Index = 0.56). Thus, selection for resistance to 4-HPR in neuroblastoma was associated with increased expression of multiple components of the anti-apoptotic sphingosine kinase signaling pathway, and such resistance can be partially overcome by targeting sphingosine kinase. 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 5262.
Synovial Fluid Tests
Authors: Robert H. Shmerling
Journal: JAMA (1990)

To determine which synovial fluid tests are most useful, we prospectively analyzed the synovial fluid test results of 100 consecutive patients undergoing diagnostic arthrocentesis. Each patient's diagnosis was established independently of synovial fluid laboratory test results; in 69 patients a definite inflammatory or noninflammatory categorization could be made. Sensitivity and specificity were estimated for synovial fluid white blood cell count (sensitivity, 0.84; specificity, 0.84), percentage of polymorphonuclear cells (sensitivity, 0.75; specificity, 0.92), glucose (sensitivity, 0.20; specificity, 0.84), protein (sensitivity, 0.52; specificity, 0.56), and lactate dehydrogenase (sensitivity, 0.83; specificity 0.71). Receiver operating characteristic regression analysis indicated that both white blood cell count and percentage of polymorphonuclear cells were found to contribute independent diagnostic information but lactate dehydrogenase did not. In a separate, retrospective analysis of 19 patients with definite septic arthritis, similar results were observed. We conclude that synovial fluid white blood cell count and percentage of polymorphonuclear cells perform well as discriminators between inflammatory and noninflammatory disease. Ordering chemistry studies of synovial fluid should be discouraged because they are likely to provide misleading or redundant information.
520. ProTIS, a Method for Prediction of Insertion-Site Preferences into Chromosomes of Vectors Used for Gene Therapy
Authors: Aron M. Geurts, Christopher S. Hackett, Jason B. Bell, Tracy L. Bergemann, Lara S. Collier, Corey M. Carlson, David A. Largaespada, Perry B. Hackett
Journal: Molecular Therapy (2006)

Retroviruses and transposons are mobile genetic elements with the ability to integrate genetic information into chromosomes for human gene therapy. However, integration-site preferences for mobile elements are poorly understood. We analyzed the insertion sites of several mobile elements to detect patterns of integration that can lead to the prediction of preferred integration sites. Based on our findings, we developed an automated method, ProTIS©, capable of faithfully predicting which base pairs in chromosomal DNA are preferred sites for Sleeping Beauty (SB) transposons. The preference for integration into certain sites is based upon structural characteristics of sequences flanking the dinucleotide insertion site. For any gene, chromosome, or whole genome, ProTIS© can generate a profile of predicted integration events. We have described an in vitro assay of transposition that uses a mathematical description of DNA deformability, Vstep, which allowed us to identify shared structural patterns among several preferred integration sites for SB transposons. For the SB transposon system we established the following equation that allows prediction of the relative likelihood of integration of an SB transposon into defined lengths of sequence: Likelihood of Integration = <sum>[10(# preferred sites) + 5(# semi-preferred sites) + (# basal sites)] ProTIS is valid for integration of SB transposons into limited and extended regions of genomic DNA up to 3.2 Mbp. We used a similar approach to analyze DNA integration patterns of other mobile genetic elements including retroviruses, lentiviruses and insect transposons. We analyzed 11,791 piggyBac integration events into its target TTAA sites and 5,070 integrations of P-elements, which do not have defined target sites. We were unable to find consistent Vstep pattern shared among either the piggyBac or P-element integration sites. We examined 695 MLV, 1371 HIV-1, 148 SIV and 551 ASLV integration sites for Vstep patterns that would aid in predicting integration preferences. Although we found symmetric patterns that overlapwith the base pairs involved in the target site duplication for most viral vectors, their patterns are based on the same compilations used to identify unique, weak consensus sequences for the various viruses and therefore cannot be used to generate algorithms for predicting integration sites based on structure rather than sequence. Our data suggest that as the density of integrations into a defined sequence increases our approach using ProTIS will have utility for human gene therapy applications for 'randomly' integrating vectors. Perry Hackett and David Largaespada have financial interests in Discovery Genomics, Inc., a Minneapolis-based startup company.
Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality
Authors: Michelle Kittleson, Shelley Hurwitz, Monica R Shah, Anju Nohria, Eldrin Lewis, Michael Givertz, James Fang, John Jarcho, Gilbert Mudge, Lynne W Stevenson
Journal: Journal of the American College of Cardiology (2003)
Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia
Authors: V Prima, L Gore, A Caires, T Boomer, M Yoshinari, M Imaizumi, M Varella-Garcia, S P Hunger
Journal: Leukemia (2005)
The effect of inhibitors of renal transport on the small intestine.
Authors: H J Binder, L A Katz, R P Spencer, H M Spiro
Journal: Journal of Clinical Investigation (1966)

In the genetically determined disorders cystinuria and Hartnup disease, amino acid transport defects are present in both the small intestine and the kidney (2-4).It would seem logical that agents which alter kidney function may also affect the transporting ability of the small intestine.We have therefore studied the effect on intestinal transport (by means of in vitro intestinal preparations) of some of the drugs that inhibit renal tubular transport. MethodsEverted gut sacs were made from the small intestine of male golden hamsters weighing between 80 and 130 g (5).The nonfasting animal was killed by a blow on the head.The small intestine was then isolated, washed in situ with pH 7.4 Krebs bicarbonate buffer, and removed by stripping off the mesentery.It was then everted, and three segments each weighing approximately 600 mg were constructed from the entire length of the bowel.The nonelectrolyte whose transport was to be studied was placed at varying concentrations in the buffer, and 1 ml of this fluid was placed inside the sac.The sac was then placed in an Erlenmeyer flask with 5 ml of buffer con- taining the nonelectrolyte at an identical concentration.Potential inhibitors at several concentrations were added to the buffer as indicated.After being gassed with 95% 02 and 5% C02, the flasks were stoppered and placed in an oscillating water bath kept at 370 C and 50 vibrations per minute for 1 hour.Portions of the serosal and mu- cosal fluids were centrifuged and then analyzed for radio- activity in a liquid scintillation spectrometer.1 Sacs were blotted and weighed.
Acute Tubular Necrosis Secondary to Rhabdomyolysis with Complete Absence of Renal Perfusion
Authors: D H PHAM, J M ASH, D L GILDAY, G ARBUS
Journal: Clinical Nuclear Medicine (1987)

Absent renal perfusion on a Tc-99m DTPA radionuclide study was observed in a patient with acute tubular necrosis following rhabdomyolysis. Complete recovery was achieved with conservative treatment. Absence of renal perfusion does not indicate a nonviable kidney.
Aurora A Kinase Inhibition Selectively Synergizes with Histone Deacetylase Inhibitor through Cytokinesis Failure in T-cell Lymphoma
Authors: Kelly M. Zullo, Yige Guo, Laurence Cooke, Xavier Jirau-Serrano, Michael Mangone, Luigi Scotto, Jennifer E. Amengual, Yinghui Mao, Renu Nandakumar, Serge Cremers, Jimmy Duong, Daruka Mahadevan, Owen A. O'Connor
Journal: Clinical Cancer Research (2015)

Aurora A kinase (AAK) is expressed exclusively during mitosis, and plays a critical role in centrosome duplication and spindle formation. Alisertib is a highly selective AAK inhibitor that has demonstrated marked clinical activity of alisertib across a spectrum of lymphomas, though particularly in patients with T-cell lymphoma (TCL). We sought to compare and contrast the activity of alisertib in preclinical models of B-cell lymphoma (BCL) and TCL, and identify combinations worthy of clinical study. High-throughput screening of pralatrexate, the proteasome inhibitor (ixazomib), and the histone deacetylase (HDAC) inhibitor (romidepsin) revealed that only romidepsin synergized with alisertib, and only in models of TCL. We discovered that the mechanism of synergy between AAK inhibitors and HDAC inhibitors appears to be mediated through cytokinesis failure.
For cancer, the good news is survival; the bad news is incidence
Authors: Phil Gunby
Journal: JAMA (1980)

If this year's census form had asked: Have you ever had cancer? a clearer picture might then emerge of the number of persons in the United States who have had or have cancer and continue to survive.  The National Cancer Institute (NCI) and the American Cancer Society (ACS) estimate that more than 3 million persons living in this country have a history of cancer and that at least 2 million of them received the initial diagnosis five or more years ago. These figures do not include skin cancers other than malignant melanoma; estimates of the number of persons who have had or have basal, squamous, or basosquamous cell carcinomas range from 400,000 to nearly 10 million.  This year, the ACS predicts that some 785,000 persons in this country—20,000 more than in 1979 and 85,000 more than in 1978—will receive diagnoses of cancer for the first time. About one in three
Specific Muscle Uptake on Bone Scintigraphy After Strenuous Activity
Authors: CLAYTON FRATER, MONICA ROSSLEIGH, PROVAN MURRAY
Journal: Clinical Nuclear Medicine (1997)

A 38-year-old woman was referred for bone scintigraphy to evaluate her left groin pain, which had been present for a number of weeks. While dynamic and blood pool images were unremarkable, static images at 2 hours demonstrated soft tissue tracer uptake in the proximal thigh muscles medially, corresponding to the adductor longus muscles of both thighs, more so on the left. While the presence of muscle uptake on bone scintigraphy has been well documented after over-strenuous activities, this case demonstrates an unusual selective uptake pattern involving the adductor thigh muscles, the specific groups subject to overuse in the patient's recent intensive horse-riding.
Incorporation of 131I-fibrinogen in a coronary artery thrombus, detected in vivo with a scintillation camera
Authors: C. B. MOSCHOS, H. A. OLDEWURTEL, K. LAHIRI, G. MANSKOPF, T. J. REGAN
Journal: Cardiovascular Research (1974)

A study was designed to evaluate scintillation images from an experimentally-induced thrombus in the anaesthetized, intact dog and explore the feasibility of detecting thrombus in the coronary artery in vivo by a non-invasive method. 131I-fibrinogen was infused systemically or into the coronary artery during the formation of a platelet thrombus with a catheter electrode. The Anger camera with pinhole collimator demonstrated only fair discrimination with systemic infusion despite substantial uptake of label in the thrombus. A clear definition of thrombus was accomplished during intracoronary infusion of isotope, largely due to the reduction of background activity from blood in the cardiac chambers. Thus, reduction of background should enable detection of a platelet thrombus in vivo, but the time limits of incorporation of label remain to be defined.
Reorganization of cholangiocyte membrane domains represents an early event in rat liver ischemia
Authors: Brian R. Doctor, Rolf H. Dahl, Kelli D. Salter, Gregory J. Fitz
Journal: Hepatology (1999)

Cholangiocytes contribute significantly to bile formation through the vectorial secretion of water and electrolytes and are a focal site of injury in a number of diseases including liver ischemia and post–transplantation liver failure. Using ischemia in intact liver and adenosine triphosphate (ATP) depletion in cultured cells to model cholangiocyte injury, these studies examined the effects of metabolic inhibition on cholangiocyte viability and structure. During 120 minutes of ischemia or ATP depletion, cell viability and tight junctional integrity in cholangiocytes were maintained. However, both the in vivo and in vitro models displayed striking alterations in the secondary structure of the plasma membrane. After 120 minutes, the basolateral (BL) interdigitations were diminished and the apical (Ap) microvilli were significantly decreased in number. The BL and Ap membrane surface areas decreased by 42 ± 8% and 63 ± 2%, respectively. Despite these changes, F–actin remained predominantly localized to the membrane domains. In contrast, in a time course that paralleled the loss of microvilli, the actin–membrane linking protein ezrin progressively dissociated from the cytoskeleton. These studies indicate that cholangiocyte ATP depletion induces characteristic, domain–specific changes in the plasma membrane and implicate alterations in the membrane–cytoskeletal interactions in the initiation of the changes. Pending the re–establishment of the differentiated domains, the loss of specific secondary structures may contribute to impaired vectorial bile duct secretion and postischemic cholestasis.
THE TREATMENT OF URETHRAL STRICTURE BY EXCISION
Authors: GRANVILLE MacGOWAN
Journal: JAMA (1923)

The important subject of the treatment of urethral stricture by excision is given very scant attention in the textbooks of general surgery, and not much more by the authors writing on the specialty of urology. Resection of strictures as a surgical procedure for effecting a relative cure of permanent duration has never gained great popularity with the surgical world, chiefly because of lack of accurate knowledge of the anatomy of the urethra and the perineum, and of the ever present fear that the removal of any portion of the corpus spongiosum will result in lasting multilation, with prevention of erection, and impotence. There has also been a natural apprehension that after the removal of sections of the canal of considerable extent, there might result a necrosis of the approximated cut ends. For these reasons, reports of resections have usually been confined to the results obtained from the removal of the
Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA.
Authors: D Tschoepe, H P Schultheiss, P Kolarov, B Schwippert, K Dannehl, H K Nieuwenhuis, B Kehrel, B Strauer, F A Gries
Journal: Circulation (1993)

BACKGROUND We wished to investigate whether platelet activation is related to the clinical outcome during the 24 hours immediately after elective percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS In 102 patients with high-grade coronary stenosis admitted for elective PTCA, preprocedural platelet activation was characterized by flow cytometric measurement of the proteins CD62, CD63, and thrombospondin expressed on the platelet surface membrane. The prevalence of acute ischemic events during the 24 hours immediately after the procedure was then related to the pre-PTCA platelet activation status. Fifty-six patients were classified as "nonactivated," whereas 46 patients showed an increased percentage of activated platelets. Two patients developed acute occlusion (1.96%) and four patients high-grade restenosis (3.92%), as confirmed by second-look coronary angiography. All events occurred in patients classified as "activated" (six of 46, or 13%). None of these patients received beta-blocker medication, which was associated with lower expression of platelet membrane activation markers. In the nonactivated patient group, no clinical events were found (0 of 56, or 0%). This difference in prevalence is significant (p = 0.007). CONCLUSIONS We conclude that analysis of platelet membrane activation markers may help to predict an increased risk of acute ischemic events after angioplasty.
Persistence of Airway Hyper-Responsiveness (AHR) after Resolution of Bronchial Mucosal Inflammation Following Allergen Inhalation Challenge in Mild Asthmatics
Authors: H.H. Kariyawasam, M. Aizen, J. Barkans, D.S. Robinson, A.B. Kay
Journal: Journal of Allergy and Clinical Immunology (2006)