tbuckley/cabot-search huggingface dataset:
US health industry to set safety guides for hospitals
Authors: Janice Hopkins Tanne
Journal: BMJ (2006)

A consortium of government and private groups working with the US National Quality Forum will soon issue a set of 30 “safe practices” that hospitals should use to reduce medical errors and prevent patient injuries and deaths. 

The “safe practices” will give hospitals uniform guidelines to improve patient safety. The forum will also help hospitals implement them. The comment period on the practices ended this week. 

The guidelines are important because hospitals that use them are likely to be preferred by consumers and government and private health insurance plans. Hospitals that do not comply might lose accreditation and reimbursement …
IMPACT OF PRIMARY PERCUTANEOUS CORONARY INTERVENTION ON GENDER DIFFERENCES IN THE EARLY MORTALITY OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION FROM A REGISTRY DATABASE IN JAPAN
Authors: TAKAFUMI YAMANE, Junichi Kotani, Hiroki Sakamoto, Akiko Kada, Kazuya Yonezawa, Masahiro Suzuki, Yukio Nakamura, Hiromi Matubara, Nobuo Fukuda, Hideo Kusuoka, Hiroyuki Yokoyama
Journal: Journal of the American College of Cardiology (2011)
ET-09 * DECOY OLIGONUCLEOTIDE DERIVED FROM MGMT ENHANCER HAS AN ANTINEOPLASTIC ACTIVITY IN-VITRO AND IN-VIVO
Authors: T. Canello, H. Ovadia, M. Refael, D. Zrihan, T. Siegal, I. Lavon
Journal: Neuro-Oncology (2014)

INTRODUCTION: Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, correlates with a better therapeutic response and with increased survival. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through binding of p65/NF-kappaB homodimers to the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer. METHODS AND RESULTS: In an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to MGMT enhancer, the potential of the MGMT-kB1-LODN to enhance cell killing was studied in vitro in two glioma cell lines (T98G and U87) and a melanoma cell line (A375P). All three cell lines manifested a significant enhanced cell killing effect following exposure to temozolomide (TMZ) when first transfected with MGMT-kb1-LODN, and also induced a significant cell killing when administered as monotherapy. These results were confirmed also in-vivo on A375P Melanoma xenografts. Intratumoral (Intralesional - IL) injection of MGMT-kB1-LODN with or without IP injection of TMZ induced significant tumor growth inhibition either as a monotherapy or in combination with TMZ. The long-term effect of MGMT-kB1-LODN monotherapy was evaluated using a repetitive IL injection every 4 to 5 days for 55 days with either MGMT-κB1 LODN or control ODN or vehicle. A significant difference (p < 0.01) in tumor volume was obtained by MGMT-κB1-LODN compared to both control groups. Moreover, two out of the seven mice treated with MGMT-κB1-LODN demonstrated tumor regression by day 55 and no tumor recurrence was observed five months later. CONCLUSION: The results of these experiments show that the MGMT-kB1-LODN has a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.
STUDIES ON VITAL STAINING
Authors: J. Victor, J. R. Van Buren, H. P. Smith
Journal: The Journal of Experimental Medicine (1930)

When brilliant vital red is injected into the blood stream of dogs much of it is slowly taken up into numerous phagocytes scattered throughout the tissues ("reticulo-endothelial system" of Aschoff). The rate at which the dye leaves the blood stream is determined in large part by the action of these phagocytic cells, but the excretion of dye into the bile is also in part responsible for the loss of dye from the plasma. The injection of a small amount of India ink into the blood stream results in lowering the rate at which the dye disappears from circulation. The fact that much of the carbon of the ink is promptly taken up by the phagocytes would lead one to suspect that they were saturated with foreign materials, or "blocked" against the entrance of dye, but it is shown that the ink causes a remarkable inhibition of the excretion of dye into the bile, and this alone seems to account for the longer retention of dye in the blood stream. There is no evidence that any of the retention is due to defective activity on the part of the phagocytes. Thus, prolonged retention of foreign materials in the blood stream cannot be cited to prove "blockade of the reticulo-endothelial system" unless one can rule out such peculiar reactions on the part of excretory organs. It is felt that the literature of "blockade" should be studied with such sources of error in mind. Preliminary studies indicate that the suppression of dye excretion by the liver is not due to the carbon content of the ink. Studies of other components of the ink are now in progress.
Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Authors: Arlene B. Chapman, Olivier Devuyst, Kai-Uwe Eckardt, Ron T. Gansevoort, Tess Harris, Shigeo Horie, Bertram L. Kasiske, Dwight Odland, York Pei, Ronald D. Perrone, Yves Pirson, Robert W. Schrier, Roser Torra, Vicente E. Torres, Terry Watnick, David C. Wheeler
Journal: Kidney International (2015)
Double-Strand Break Damage and Associated DNA Repair Genes Predispose Smokers to Gene Methylation
Authors: Shuguang Leng, Christine A. Stidley, Randy Willink, Amanda Bernauer, Kieu Do, Maria A. Picchi, Xin Sheng, Melissa A. Frasco, David Van Den Berg, Frank D. Gilliland, Christopher Zima, Richard E. Crowell, Steven A. Belinsky
Journal: Cancer Research (2008)

Gene promoter hypermethylation in sputum is a promising biomarker for predicting lung cancer. Identifying factors that predispose smokers to methylation of multiple gene promoters in the lung could affect strategies for early detection and chemoprevention. This study evaluated the hypothesis that double-strand break (DSB) repair capacity and sequence variation in genes in this pathway are associated with a high methylation index in a cohort of current and former cancer-free smokers. A 50% reduction in the mean level of DSB repair capacity was seen in lymphocytes from smokers with a high methylation index, defined as three or more of eight genes methylated in sputum, compared with smokers with no genes methylated. The classification accuracy for predicting risk for methylation was 88%. Single nucleotide polymorphisms within the MRE11A, CHEK2, XRCC3, DNA-PKc, and NBN DNA repair genes were highly associated with the methylation index. A 14.5-fold increased odds for high methylation was seen for persons with seven or more risk alleles of these genes. Promoter activity of the MRE11A gene that plays a critical role in recognition of DNA damage and activation of ataxia-telangiectasia mutated was reduced in persons with the risk allele. Collectively, ours is the first population-based study to identify DSB DNA repair capacity and specific genes within this pathway as critical determinants for gene methylation in sputum, which is, in turn, associated with elevated risk for lung cancer.
The draft genome of watermelon (Citrullus lanatus) and resequencing of 20 diverse accessions
Authors: Shaogui Guo, Jianguo Zhang, Honghe Sun, Jerome Salse, William J Lucas, Haiying Zhang, Yi Zheng, Linyong Mao, Yi Ren, Zhiwen Wang, Jiumeng Min, Xiaosen Guo, Florent Murat, Byung-Kook Ham, Zhaoliang Zhang, Shan Gao, Mingyun Huang, Yimin Xu, Silin Zhong, Aureliano Bombarely, Lukas A Mueller, Hong Zhao, Hongju He, Yan Zhang, Zhonghua Zhang, Sanwen Huang, Tao Tan, Erli Pang, Kui Lin, Qun Hu, Hanhui Kuang, Peixiang Ni, Bo Wang, Jingan Liu, Qinghe Kou, Wenju Hou, Xiaohua Zou, Jiao Jiang, Guoyi Gong, Kathrin Klee, Heiko Schoof, Ying Huang, Xuesong Hu, Shanshan Dong, Dequan Liang, Juan Wang, Kui Wu, Yang Xia, Xiang Zhao, Zequn Zheng, Miao Xing, Xinming Liang, Bangqing Huang, Tian Lv, Junyi Wang, Ye Yin, Hongping Yi, Ruiqiang Li, Mingzhu Wu, Amnon Levi, Xingping Zhang, James J Giovannoni, Jun Wang, Yunfu Li, Zhangjun Fei, Yong Xu
Journal: Nature Genetics (2012)

Zhangjun Fei and colleagues report the draft genome of a Chinese elite watermelon inbred line 97103 and resequencing of 20 diverse accessions that represent the three subspecies of Citrullus lunatus. Comparative genome-wide analyses identify the extent of genetic diversity and population structure of watermelon germplasm. Watermelon, Citrullus lanatus, is an important cucurbit crop grown throughout the world. Here we report a high-quality draft genome sequence of the east Asia watermelon cultivar 97103 (2n = 2× = 22) containing 23,440 predicted protein-coding genes. Comparative genomics analysis provided an evolutionary scenario for the origin of the 11 watermelon chromosomes derived from a 7-chromosome paleohexaploid eudicot ancestor. Resequencing of 20 watermelon accessions representing three different C. lanatus subspecies produced numerous haplotypes and identified the extent of genetic diversity and population structure of watermelon germplasm. Genomic regions that were preferentially selected during domestication were identified. Many disease-resistance genes were also found to be lost during domestication. In addition, integrative genomic and transcriptomic analyses yielded important insights into aspects of phloem-based vascular signaling in common between watermelon and cucumber and identified genes crucial to valuable fruit-quality traits, including sugar accumulation and citrulline metabolism.
CULTURAL STUDIES ON MOUTH SPIROCHÆTÆ (TREPONEMA MICRODENTIUM AND MACRODENTIUM)
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1912)

I have described the successful cultivation of two distinct species of Treponema from the oral cavity of man. The species differ from one another morphologically and in respect to their cultural properties. As the two species have now been clearly separated and cultivated for the first time, I propose for them the names Treponema microdentium and macrodentium, respectively. Division along the longitudinal axis has been demonstrated for both Treponema macrodentium and microdentium. When the micro- and macrodentium are cultivated under imperfect anaerobic conditions, they undergo involution, but still continue to vegetate to some extent. Finally, a spiral organism has been cultivated and described that may be merely an involuted form of the macrodentium, or it may be a new species altogether.
Higher folic acid levels could reduce risk of Alzheimer's disease
Authors: S. Gottlieb
Journal: BMJ (2002)

High levels of the amino acid homocysteine may increase the risk of developing Alzheimer's disease, a new study has shown. The risk of Alzheimer's disease was found to be nearly doubled in people with high levels of homocysteine.

The study raises the possibility of staving off dementia by consuming more folic acid and vitamins B-6 and B-12, which can lower homocysteine levels. But one of the study's authors emphasised that …
Breathless beyond obvious
Authors: C. Bloom
Journal: BMJ (2008)

A 56 year old woman with endometrial leiomyosarcoma and metastatic involvement of her lungs presented with a three day history of acute breathlessness from a background of intermittent breathlessness. Two months previously she had started chemotherapy with gemcitabine and docetaxel, and three days before admission she had completed her third cycle. A computed tomography scan done two weeks earlier showed minimal change in the bulk of the cancer, but a filling defect in her iliac vein was seen. Thrombosis was suspected, and anticoagulation treatment was started. The woman denied any cough, haemoptysis, fevers, or pain. On examination she had normal bilateral breath sounds, a respiratory rate of 35 breaths per minute, oxygen saturation of 87% on 15 l/min oxygen, a temperature of 38°C, heart rate sinus 120 beats per minute, blood pressure of 90/60 mm Hg, and normal heart sounds. The only abnormality on her chest radiograph was pulmonary metastases. Her respiratory and haemodynamic compromise was thought to be caused by a pulmonary embolism, and she was given 250 ml of intravenous colloid. This increased her tachypnoea, and new bilateral wheeze was heard on auscultation. A computed tomography pulmonary angiogram was performed and showed a filling defect in her right ventricle, diffuse bilateral pulmonary infiltrates, but no filling defects in her pulmonary vessels. ### Short Answers
Glyburide-Induced Hepatitis
Authors: RALPH C. GOODMAN
Journal: Annals of Internal Medicine (1987)

Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.
CELLULAR BASIS OF THE GENETIC CONTROL OF IMMUNE RESPONSES TO SYNTHETIC POLYPEPTIDES
Authors: Edna Mozes, G. M. Shearer, Michael Sela
Journal: The Journal of Experimental Medicine (1970)

SJL mice are high responders to the synthetic multichain polypeptide antigen (T,G)-Pro--L, whereas DBA/1 mice are low responders (10, 11). In order to determine whether the genetic control of immune response can be correlated with the number of antigen-sensitive precursor cells, spleen cell suspensions from normal and immunized SJL and DBA/1 donor mice were transplanted into lethally X-irradiated syngeneic recipients (incapable of immune response) along with (T, G)-Pro--L. Anti-(T, G)-Pro--L responses (donor-derived) were assayed in the sera of the hosts 12-16 days later. By transplanting graded and limiting numbers of spleen cells, inocula were found which contained one or a few antigen-sensitive precursors reactive with the immunogen. Using this method to estimate the relative numbers of such cells for the high responder SJL strain, one precursor was detected in approximately 1.3 x 10(6) and approximately 7.2 x 10(6) spleen cells from immunized and normal donors, respectively. In contrast, one precursor was detected in about 30 x 10(6) spleen cells from low responder DBA/1 mice, irrespective of whether the donors had been immunized. These results indicate that the genetic control of immunity to the synthetic polypeptide antigen investigated is directly correlated to the relative number of precursor cells reactive with the immunogen in high and low responder strains.
Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10
Authors: Takashi Murakami, Adela R. Cardones, Steven E. Finkelstein, Nicholas P. Restifo, Brenda A. Klaunberg, Frank O. Nestle, S. Sianna Castillo, Phillip A. Dennis, Sam T. Hwang
Journal: The Journal of Experimental Medicine (2003)

Human melanoma cells frequently express CC chemokine receptor (CCR)10, a receptor whose ligand (CCL27) is constitutively produced by keratinocytes. Compared with B16 murine melanoma, cells rendered more immunogenic via overexpression of luciferase, B16 cells that overexpressed both luciferase and CCR10 resisted host immune responses and readily formed tumors. In vitro, exposure of tumor cells to CCL27 led to rapid activation of Akt, resistance to cell death induced by melanoma antigen-specific cytotoxic T cells, and phosphatidylinositol-3-kinase (PI3K)–dependent protection from apoptosis induced by Fas cross-linking. In vivo, cutaneous injection of neutralizing antibodies to endogenous CCL27 blocked growth of CCR10-expressing melanoma cells. We propose that CCR10 engagement by locally produced CCL27 allows melanoma cells to escape host immune antitumor killing mechanisms (possibly through activation of PI3K/Akt), thereby providing a means for tumor progression.
Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: Short-term and long-term outcomes
Authors: Diarmaid D. Houlihan, Laurence J. Hopkins, Shankar X. Suresh, Matthew J. Armstrong, Philip N. Newsome
Journal: Hepatology (2011)

We read with interest the article by Peng et al. investigating the potential beneficial effects of culture expanded autologous mesenchymal stem cells (MSCs) in patients with liver failure caused by hepatitis B virus (HBV).1 Though it is reassuring that MSC therapy delivered via the hepatic artery in this group of patients appears to be safe and feasible, there are several areas of the article that would benefit from clarification. It would be helpful if the investigators could provide data regarding HBV viral load, genotype, and E antigen status for each patient in the trial, as they are important risk factors for progressive liver disease and hepatocellular carcinoma.2, 3 These data, in addition to hepatitis C virus coinfection, are required before robust conclusions about the efficacy of MSC therapy can be made. Patients on antiviral treatment were excluded from the trial. We would like the investigators to clarify whether HBV antiviral therapy was given at any time to the enrolled patients. This is of importance, because the efficacy of antiviral therapy in this patient group has been well established for over a decade.4, 5 In contrast, the antiviral, antifibrotic, and regenerative effects of MSCs have not been proven.6 Furthermore, the surface expression of cluster of differentiation (CD)73, CD90, CD105, and evidence of trilineage differentiation, which are required to define a pure MSC population, have not been provided.7 The article would benefit from inclusion of such data, because culture-expanded MSCs are frequently heterogeneous and can contain contaminating cells.8 In summary, we feel additional data are required before firm conclusions about the efficacy of MSC therapy in HBV liver failure can be made. Moreover, MSC therapy should only be considered after an optimization of antiviral therapy in future clinical trials. Diarmaid D. Houlihan* , Laurence J. Hopkins*, Shankar X. Suresh*, Matthew J. Armstrong* , Philip N. Newsome* , * Center for Liver Research, National Institute for Health Research, University of Birmingham, Birmingham, UK, Liver Unit, Queen Elizabeth Hospital, University Hospital Birmingham National Health Service Foundation Trust Birmingham, UK.
Mammosomatotropes: Presence and Functions in Normal and Neoplastic Pituitary Tissue*
Authors: L. STEPHEN FRAWLEY, F. R. BOOCKFOR
Journal: Endocrine Reviews (1991)

MORE than a half century has passed since Romeis first proposed the "one cell-one hormone" theory which holds that each of the major pituitary hormones is produced by a separate and distinct cell type (1). Consistent with this idea, the acidophilic staining cells (termed acidophils) of the adenohypophysis have been traditionally subdivided into two categories, those that secrete only GH and others that produce just PRL. This view was supported by considerable tinctorial evidence available at the time of Romeis' hypothesis and generated in the subsequent three decades (1–5). Moreover, data produced throughout the 1970s and early 1980s by the use of light microscopic immunocytochemistry (ICC) and immunofluorescence were generally consonant with the one cell-one hormone theory, except in the case of certain pituitary tumors (6–8). The presence of bihormonal acidophils in this latter situation was attributed to aberrant mechanisms attendant to the neoplastic condition. However, as will be discussed in detail later, the utilization of even newer techniques with greater powers of resolution and sensitivity has radically changed the unihormonal view of acidophil function.
Ranolazine Stimulates Glucose Oxidation in Normoxic, Ischemic, and Reperfused Ischemic Rat Hearts
Authors: James G. McCormack, Rick L. Barr, Andrew A. Wolff, Gary D. Lopaschuk
Journal: Circulation (1996)

Background Ranolazine is a novel antianginal agent that may reduce symptoms without affecting hemodynamics and has shown cardiac antiischemic effects in in vivo and in vitro models. In one study it increased active pyruvate dehydrogenase (PDHa). Other agents that increase PDHa and so increase glucose and decrease fatty acid (FA) oxidation are beneficial in ischemic-reperfused hearts. Effects of ranolazine on glucose and palmitate oxidation and glycolysis were assessed in isolated rat hearts. Methods and Results Working hearts were perfused with Krebs-Henseleit buffer plus 3% albumin under normoxic conditions and on reperfusion after 30-minute no-flow ischemia and under conditions designed to give either low [low (Ca) (1.25 mmol/L), high [FA] (1.2 mmol/L palmitate); with/without insulin] or high (2.5 mmol/L Ca, 0.4 mmol/L palmitate; with/without pacing) glucose oxidation rates; Langendorff-perfused hearts (high Ca, low FA) were subjected to varying degrees of low-flow ischemia. Glycolysis and glucose oxidation were measured with the use of [5- 3 H/U- 14 C]-glucose and FA oxidation with the use of [1- 14 C]- or [9,10- 3 H]-palmitate. In working hearts, 10 μmol/L ranolazine significantly increased glucose oxidation 1.5-fold to 3-fold under conditions in which the contribution of glucose to overall ATP production was low (low Ca, high FA, with insulin), high (high Ca, low FA, with pacing), or intermediate. In some cases, reductions in FA oxidation were seen. No substantial changes in glycolysis were noted with/without ranolazine; rates were ≈10-fold glucose oxidation rates, suggesting that pyruvate supply was not limiting. Insulin increased basal glucose oxidation and glycolysis but did not alter ranolazine responses. In normoxic Langendorff hearts (high Ca, low FA; 15 mL/min), all basal rates were lower compared with working hearts, but 10 μmol/L ranolazine similarly increased glucose oxidation; ranolazine also significantly increased it during flow reduction to 7, 3, and 0.5 mL/min. Ranolazine did not affect baseline contractile or hemodynamic parameters or O 2 use. In reperfused ischemic working hearts, ranolazine significantly improved functional outcome, which was associated with significant increases in glucose oxidation, a reversal of the increased FA oxidation seen in control reperfusions (versus preischemic), and a smaller but significant increase in glycolysis. Conclusions Beneficial effects of ranolazine in cardiac ischemia/reperfusion may be due, at least in part, to a stimulation of glucose oxidation and a reduction in FA oxidation, allowing improved ATP/O 2 and reduction in the buildup of H + , lactate, and harmful fatty acyl intermediates.
The Value of Cardiology
Authors: Lee Goldman
Journal: New England Journal of Medicine (1996)

It seems just yesterday that the value of specialty training was unchallenged and the health benefits associated with the care and procedures provided by subspecialists were unquestioned. In cardiology, for example, the extra two or three years of clinical training were assumed to translate into improved clinical skills for treating patients with cardiac disorders.Cardiologists led the way in performing large-scale, randomized trials to demonstrate the benefits of medications and procedures in patients with acute myocardial infarction, chronic ischemic heart disease, or congestive heart failure. Not surprisingly, age-adjusted rates of mortality due to coronary heart disease in the United States . . .