tbuckley/cabot-search huggingface dataset:
Signal Transducers and Activators of Transcription 3 Activation Is Involved in Nuclear Accumulation of β-Catenin in Colorectal Cancer
Authors: Mayumi Kawada, Hiroshi Seno, Yoshito Uenoyama, Tateo Sawabu, Naoki Kanda, Hirokazu Fukui, Yasuyuki Shimahara, Tsutomu Chiba
Journal: Cancer Research (2006)

Nuclear accumulation of beta-catenin is a key event for the development of colorectal cancer. Little is known, however, about the mechanisms underlying translocation of beta-catenin from the cytoplasm or the membrane to the nucleus. The present study examined whether signal transducers and activators of transcription 3 (STAT3) activation is involved in the nuclear accumulation of beta-catenin in colorectal cancer cells. Of the 90 primary colorectal cancer tissues, 40 (44.4%) were positive for nuclear staining of p-STAT3 and 63 (70.0%) were positive for nuclear staining of beta-catenin. The nuclear staining of both p-STAT3 and beta-catenin were observed predominantly in the periphery of the cancer tissues. Importantly, of the 40 tumors with p-STAT3 nuclear staining, 37 (92.5%) were also positive for nuclear beta-catenin staining and there was a significant correlation between p-STAT3 and beta-catenin nuclear staining (P < 0.01). Coexpression of nuclear p-STAT3 and beta-catenin was associated with lower patient survival (P < 0.01). In an in vitro study using a human colon cancer cell line, SW480, inhibition of STAT3 by dominant negative STAT3 or the Janus kinase inhibitor, AG490, induced translocation of beta-catenin from the nucleus to the cytoplasm or membrane. Luciferase assays revealed that STAT3 inhibition resulted in significant suppression of beta-catenin/T-cell factor transcription in association with significant inhibition of cell proliferation (P < 0.05). These findings suggest that in colorectal cancer, STAT3 activation is involved in the nuclear accumulation of beta-catenin, resulting in poor patient survival.
Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia
Authors: Stephen Breit, Martin Stanulla, Thomas Flohr, Martin Schrappe, Wolf-Dieter Ludwig, Gabriele Tolle, Margit Happich, Martina U. Muckenthaler, Andreas E. Kulozik
Journal: Blood (2006)
XIV. Cardiac Arrest
Authors: Joseph V. Messer
Journal: New England Journal of Medicine (1966)

THE management of cardiac arrest to be described applies to the hospital environment, and assumes the prior provision of adequate resuscitation equipment and established guidelines for selection of patients in whom resuscitation will be attempted.Definition of Cardiac ArrestCardiac arrest may be defined as the sudden and unexpected cessation of effective circulation, resulting in inadequate delivery of oxygenated blood to vital organs.General Principles of ManagementAttempts at cardiac resuscitation are based on the premise that a period of potential reversibility exists in nearly all cases of cardiac arrest. The duration of this period is usually four to six . . .
Respiratory muscle response to flail chest.
Authors: M Cappello, C Yuehua, A De Troyer
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We have previously shown that flail chest in the dog causes an inspiratory inward displacement of the ribs and an increased inspiratory activity in the external intercostal muscles, and we have speculated that this increased activity is due to an increased spindle afferent activity. The present studies were designed to test this hypothesis. Twenty-nine supine anesthetized dogs were studied, and flail was produced surgically by fracturing ventrally and dorsally two to four contiguous ribs on the right side of the chest. Although flail elicited an increased inspiratory activity in the external intercostal and levator costae muscles in the disconnected segment of the rib cage, it did not alter the inspiratory activity in the diaphragm and parasternal intercostals. Expiratory activity in the triangularis sterni, internal intercostals, and transversus abdominis remained unchanged also, as did the inspiratory activity in the external intercostals on the left side of the chest. After flail, the normal inspiratory shortening of the external intercostal muscles in the disconnected segment was also reversed into an inspiratory muscle lengthening. However, when the fractured ribs were connected to the adjacent ribs so that the external intercostals were prevented from lengthening during inspiration, external intercostal and levator costae inspiratory activity was unaltered. These observations support the hypothesis that the increased external intercostal muscle activity seen in flail chest results primarily from an increased activation of the muscle spindles.
Annular Stricture of the Intestine: its Diagnosis and Treatment
Authors: S. Mackenzie
Journal: BMJ (1879)

Ainos are rare in collections at present, though some observations upon them have been published by Barnard Davis and Busk.The few skulls known are heavy, and have the muscular impressions strongly marked.The average altitudinal index of four in Dr. Barnard Davis's collection is 78; of three measured by Professor Flower, 74.3.These present none of the features characteristic of Mongolian skulls, the facial bones being more European in type, the nasi-malar angle only 129 deg.The affinities of the Ainos are at present matter for speculation.If Caucasian, it is difficult to account for their local posi- tion.The hypothesis that they are a remnant of a race from whom the aboriginal population of the Indian Peninsula and perhaps the Australians are derived is tempting, but hardly as yet supported by facts.E. S. Morse, from examination of the pottery and implements found in ancient kitchen-middens in Japan, has recently been led to the conclu- sion that another race inhabited the country before the Ainos ; but if this were the case, we know nothing at present of their physical cha- 'racters.
T‐ and B‐cell subsets in periodontitis
Authors: José R. Gonzales
Journal: Periodontology 2000 (2015)

Abstract A large amount of information is available, in the medical literature, on the molecular and immunological mechanisms in which T‐ and B‐cells are involved in the pathogenesis of inflammatory diseases. This review attempts to describe the most important features of the T‐cell subsets and their cytokine networks in periodontitis, including the interaction of pathogens with different cell subsets and their gene‐expression profiles. Additionally, the known interactions of T‐ and B‐cell subsets in periodontitis are described. The purpose of this article was to provide an overview of the cell interactions and cytokine networks specifically involved in the pathogenesis of periodontitis, and models and paradigms from recent research in this area are presented. However, the review of the literature also revealed that relatively little is known about the genetic or structural factors that confer cross‐reactivity of natural and/or autoreactive antibodies in the immunopathogenesis of periodontitis. Pathogens, in turn, are continuously evolving and creating mechanisms to evade immunological reactions controlled and modulated by T‐ and B‐cells.
IMMUNOLOGICAL STUDIES ON A NEW PREPARATION OF TYPE SPECIFIC POLYSACCHARIDE FROM PNEUMOCOCCUS TYPE I
Authors: Bacon F. Chow
Journal: The Journal of Experimental Medicine (1936)

A type specific polysaccharide has been isolated from the autolyzed broth of Type I Pneumococcus by a modified Avery and Goebel's method. The newly prepared polysaccharide reacts with the homologous immune rabbit serum which has been completely absorbed with the acetyl polysaccharide of Avery and Goebel. The newly prepared polysaccharide produces passive immunity in mice and rats and possibly in rabbits. The antigenicity is not lost on boiling in acid or alkaline medium, but the precipitative activity is decreased. In conclusion, it has been shown that the polysaccharide from Type I Pneumococcus, as isolated by a slight modification of Avery and Goebel's method, is a more complete antigen.
Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: a novel epigenetic-targeting approach in acute myeloid leukemia
Authors: A Mims, A R Walker, X Huang, J Sun, H Wang, R Santhanam, A M Dorrance, C Walker, P Hoellerbauer, S S Tarighat, K K Chan, R B Klisovic, D Perrotti, M A Caligiuri, J C Byrd, C-S Chen, L James Lee, S Jacob, K Mrózek, C D Bloomfield, W Blum, R Garzon, S Schwind, G Marcucci
Journal: Leukemia (2012)
Cardiac angiotensinogen and its local activation in the isolated perfused beating heart.
Authors: K Lindpaintner, M W Jin, N Niedermaier, M J Wilhelm, D Ganten
Journal: Circulation Research (1990)

Increasing evidence suggests that the renin-angiotensin system modulates cardiovascular homeostasis both via its circulating, plasma-borne components and through locally present, tissue-resident systems with site-specific activity. The existence of such a system in the heart has been proposed, based on biochemical studies as well as on the demonstration of renin and angiotensinogen messenger RNA in cardiac tissue. We conducted the present study to determine whether biologically active angiotensin peptides may be cleaved within the heart from locally present angiotensinogen. Isolated, perfused rat hearts were exposed to infusions of purified hog renin; the coronary sinus effluent was collected and subsequently assayed for angiotensin I (Ang I) and angiotensin II (Ang II) by high-pressure liquid chromatography and specific radioimmunoassay. Both Ang I and II were undetectable under control conditions but appeared promptly after the addition of renin. Dose-dependent peak values for Ang I release ranged from 2.42 +/- 0.65 fmol/min to 1.38 +/- 0.18 pmol/min during renin infusions at concentrations between 10 microunits/ml and 5 milliunits/ml. Ang II levels measured in the perfusate reflected a mean fractional intracardiac conversion of Ang I to Ang II of 7.18 +/- 1.09%. Generation of Ang I and Ang II was inhibited in the presence of specific inhibitors of renin and converting enzyme, respectively. To investigate the source of angiotensinogen, we measured spontaneous angiotensinogen release from isolated perfused hearts. In the absence of renin in the perfusate, angiotensinogen was initially released in high, but rapidly declining, concentrations and subsequently at a low, but stable, rate. Prior perfusion with angiotensinogen-rich plasma resulted in enhanced early angiotensinogen release but did not alter the second, delayed phase, suggesting that, in addition to plasma-derived substrate, locally produced angiotensinogen may also participate in the intracardiac formation of angiotensin. Supporting this interpretation, hearts from animals pretreated with dexamethasone showed increased angiotensinogen messenger RNA concentrations as well as increased rates of angiotensinogen release not only during the early but also during the late phase. Our study newly demonstrates that Ang I and II may be formed within the isolated heart from locally present substrate, which appears to be derived in part from the circulating pool and in part from endogenous synthesis. These findings add support to the concept of a functionally active and locally integrated cardiac renin-angiotensin system and emphasize its potential physiological and pathological relevance.
Teaching the Simple Suture to Medical Students for Long-term Retention of Skill
Authors: Ethan Routt, Yasaman Mansouri, Ellen H. de Moll, Daniel M. Bernstein, Sebastian G. Bernardo, Jacob Levitt
Journal: JAMA Dermatology (2015)

Instructional methods for the simple suture technique vary widely and are seldom based on educational research. Published data indicate that video primers and structured instruction and evaluation decrease learning time and improve skill acquisition.To determine the amount of practice needed to attain simple suture proficiency and to identify the optimal teaching schedule for retention of skill.First-year and second-year medical students at the Icahn School of Medicine at Mount Sinai with little to no suturing experience were randomly divided into 2 equal groups, with one being taught on day 1 and tested for proficiency on day 30 (control group) and the other being taught on day 1 and tested for proficiency on days 10, 20, and 30 (experimental group). Students were evaluated using the objective structured assessment of technical skills method and a checklist. Those initially not proficient on a given day were immediately prompted to practice and retest. This cycle continued until proficiency was achieved for that day. The study was conducted from April 7, 2014, to June 30, 2014.Simple suture proficiency at 30 days and the mean number of practice sutures needed for proficiency on day 1.All students ultimately achieved proficiency. The mean (SD) number of practice sutures required to achieve proficiency at the initial training was 41 (15). Students in the control group had a 0% pass rate at the 30-day initial proficiency test, while students in the experimental group had a 91.7% pass rate at day 30 (P < .001). There were no differences in instructional time, cumulative number of sutures, or objective structured assessment of technical skills scores at proficiency between groups across the study.Single instructional sessions may not be sufficient to maintain simple suture proficiency over the course of a 30-day elective. We propose the use of preparatory instructional videos, followed by instructor demonstration to introduce the technique. Independent practice with intermittent evaluation and critique allows for skill acquisition and time efficiency at the initial training. Students should view instructional videos and practice at least 10 repetitions every 10 days to maintain their skill.
Principles of brain connectivity organization
Authors: Claus C. Hilgetag
Journal: Behavioral and Brain Sciences (2006)

Increases of absolute brain size during evolution reinforced stronger structuring of brain connectivity. One consequence is the hierarchical cluster structure of neural systems that combines predominantly short, but not strictly minimal, wiring with short processing pathways. Principles of “large equals well-connected” and “minimal wiring” do not completely account for observed patterns of brain connectivity. A structural model promises better predictions.
Flu: A Medical Mystery
Authors: Vittal Katikireddi
Journal: BMJ (2004)

BBC Radio 4, 2 February at 8 pm Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Aspate of high-profile infectious threats has gripped the public psyche over the past few years. Coming amid reports of a rise in avian flu and a year after the outbreak of severe acute respiratory syndrome (SARS), this programme, which looked at the influenza pandemic of 1918, was timely. The 1918 flu was one of the most devastating disease outbreaks of all time, killing 50 million people worldwide Witnesses reported the effects on family and society, as well … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Periumbilical Uptake of Tc-99m MAA on Lung Perfusion Scanning in a Patient With Superior Vena Cava Obstruction
Authors: H Balink, J Nabers
Journal: Clinical Nuclear Medicine (2006)

A 25-year-old woman with severe parenchymal lung disease of unknown etiology and existing for more than a decade was referred for ventilation–perfusion scintigraphy because of suspicion of pulmonary embolism. Both ventilation and perfusion images showed, apart from perfusion defects from her severe lung disease, a left apical pneumothorax and signs of recurrent pneumonia of the left lower lobe. Noteworthy was the periumbilical uptake of the Tc-99m macroaggregated albumin (MAA). Her medical history revealed iatrogenic superior vena cava (SVC) obstruction. In this case, the main collateral pathway of portosystemic shunting is probably, after recanalization of the left umbilical vein, a network of smaller paraumbilical veins.
Twist Transcriptionally Up-regulates AKT2 in Breast Cancer Cells Leading to Increased Migration, Invasion, and Resistance to Paclitaxel
Authors: George Z. Cheng, Joseph Chan, Qi Wang, Weizhou Zhang, Calvin D. Sun, Lu-Hai Wang
Journal: Cancer Research (2007)

Metastasis, the cardinal feature of malignant tumors, is an important clinical variable in patient prognosis. To understand the basis for metastasis, we systematically selected for highly invasive cells from breast cancer cell lines, MCF7 and MDA-MB-453, with moderate to low invasive ability using Boyden chamber invasion assay. The four-cycle selected invasive lines, named MCF7-I4 and MDA-MB-453-I4, respectively, displayed epithelial-mesenchymal transition (EMT) and dramatically enhanced invasive ability. EMT changes were corroborated with decreased level of E-cadherin and increased vimentin, fibronectin, and beta(1) integrin. Twist, a basic helix-loop-helix transcription factor, and AKT2, a known proto-oncogene, were found to be elevated in the invasive cells compared with the parental. Ectopic expression and knockdown of Twist by short interference RNA resulted in significant increase and reduction, respectively, of AKT2 protein and mRNA expression. Twist bound to E-box elements on AKT2 promoter and enhanced its transcriptional activity. Moreover, silencing AKT2 decreased Twist-promoted migration, invasion, and paclitaxel resistance. Reintroducing AKT2 largely rescued the phenotype resulted from knockdown of Twist in I4 cells, suggesting that AKT2 is a downstream target and functional mediator of Twist. Finally, we observed a 68.8% correlation of elevated Twist and AKT2 expression in late-stage breast cancers as oppose to 13% in early-stage breast cancers. Our study identifies Twist as a positive transcriptional regulator of AKT2 expression, and Twist-AKT2 signaling is involved in promoting invasive ability and survival of breast cancer cells.
Prenatal exposures to phthalates among women in New York City and Krakow, Poland.
Authors: Jennifer J Adibi, Frederica P Perera, Wieslaw Jedrychowski, David E Camann, Dana Barr, Ryszard Jacek, Robin M Whyatt
Journal: Environmental Health Perspectives (2003)

Experimental evidence has shown that certain phthalates can disrupt endocrine function and induce reproductive and developmental toxicity. However, few data are available on the extent of human exposure to phthalates during pregnancy. As part of the research being conducted by the Columbia Center for Children's Environmental Health, we have measured levels of phthalates in 48-hr personal air samples collected from parallel cohorts of pregnant women in New York, New York, (n = 30) and in Krakow, Poland (n = 30). Spot urine samples were collected during the same 48-hr period from the New York women (n = 25). The following four phthalates or their metabolites were measured in both personal air and urine: diethyl phthalate (DEP), dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP), and butyl benzyl phthalate (BBzP). All were present in 100% of the air and urine samples. Ranges in personal air samples were as follows: DEP (0.26-7.12 microg/m3), DBP (0.11-14.76 microg/m3), DEHP (0.05-1.08 microg/m3), and BBzP (0.00-0.63 microg/m3). The mean personal air concentrations of DBP, di-isobutyl phthalate, and DEHP are higher in Krakow, whereas the mean personal air concentration of DEP is higher in New York. Statistically significant correlations between personal air and urinary levels were found for DEP and monoethyl phthalate (r = 0.42, p < 0.05), DBP and monobutyl phthalate (r = 0.58, p < 0.01), and BBzP and monobenzyl phthalate (r = 0.65, p < 0.01). These results demonstrate considerable phthalate exposures during pregnancy among women in these two cohorts and indicate that inhalation is an important route of exposure.
Metabolic damage to human saphenous vein during preparation for coronary artery bypass grafting
Authors: G D ANGELINI, I. M BRECKENRIDGE, E. G BUTCHART, S. H ARMISTEAD, K. M MIDDLETON, A. H HENDERSON, A. C NEWBY
Journal: Cardiovascular Research (1985)

Segments of saphenous vein from patients undergoing coronary artery by-pass graft surgery were frozen in liquid nitrogen immediately on dissection (control), after stripping of the adventitia and side branch ligation (manipulation), after distention with blood (distention), or at completion of the last proximal anastomosis (prepared vein). Vein was stored during the operation in patient's heparinised arterial blood at room temperature. Frozen vein was extracted with perchloric acid. ATP, ADP, and AMP, adenosine, inosine and hypoxanthine concentrations were measured by high pressure liquid chromatography. Prepared vein had ca 50% lower ATP concentrations and ATP/ADP ratio than control vein, higher concentrations of inosine and hypoxanthine and lower concentrations of AMP and adenosine. ATP concentration and ATP/ADP ratio did not correlate with the time elapsed between dissection and freezing of the prepared vein. The characteristic changes seen in prepared vein were not seen when control vein was simply stored in arterial blood at 23 degrees C, in normal saline at 23 degrees C or 4 degrees C, in Krebs-Ringer bicarbonate buffer at 37 degrees C or at St Thomas's Hospital cardioplegic solution at 4 degrees C. Distention with unlimited pressure did not distension at less than 300 mmHg gave rise to the same changes in ATP concentration and ATP/ADP ratio as in the prepared vein. These results show that vein suffered metabolic changes during preparation for bypass grafting and suggest that uncontrolled distention may contribute to these changes. Such biochemical measurements provide a quantitative estimate of tissue damage and allow objective comparison of different preparative techniques.
Activation of heat shock protein (hsp)70 and proto-oncogene expression by alpha1 adrenergic agonist in rat aorta with age.
Authors: J H Chin, M Okazaki, Z W Hu, J W Miller, B B Hoffman
Journal: Journal of Clinical Investigation (1996)

Induction of heat shock proteins (hsp) most likely is a homeostatic mechanism in response to metabolic and environmental insults. We have investigated signal transduction mechanisms involved in alpha1, adrenergic receptor stimulation of hsp7O gene expression in isolated aortas with age. We found that alpha1 adrenergic agonists directly induced hsp70 mRNA in rat aorta in vitro; the alpha1, selective antagonist prazosin blocked this effect whereas chloroethylclonidine, an antagonist which has some selectivity for alpha1B receptors, was ineffective. This response was insensitive to pertussis toxin and was partially blocked by the protein kinase C inhibitor H7. Removal of extracellular calcium attenuated induction of hsp70 mRNA but not the induction of c-fos or c-myc. The induction of hsp70 mRNA by either norepinephrine or by phorbol dibutyrate was blunted in aortas from old (24-27 mo) rats whereas c-fos responses were not diminished in the older vessels. The hsp70 response to elevated temperature (42 degrees C) was not changed with age. Activation of hsp70 expression most likely involves a pertussis toxin insensitive G protein which activates protein kinase C, and requires extracellular calcium. With age, hsp70 gene expression induced by stimulation of alpha1 adrenergic receptors is markedly attenuated, which could modify responses to stress or vascular injury with aging.