tbuckley/cabot-search huggingface dataset:
Molecular Characterization of Choroid Plexus Tumors Reveals Novel Clinically Relevant Subgroups
Authors: Diana M. Merino, Adam Shlien, Anita Villani, Malgorzata Pienkowska, Stephen Mack, Vijay Ramaswamy, David Shih, Ruth Tatevossian, Ana Novokmet, Sanaa Choufani, Rina Dvir, Myran Ben-Arush, Brent T. Harris, Eugene I. Hwang, Rishi Lulla, Stefan M. Pfister, Maria Isabel Achatz, Nada Jabado, Jonathan L. Finlay, Rosanna Weksberg, Eric Bouffet, Cynthia Hawkins, Michael D. Taylor, Uri Tabori, David W. Ellison, Richard J. Gilbertson, David Malkin
Journal: Clinical Cancer Research (2014)

To investigate molecular alterations in choroid plexus tumors (CPT) using a genome-wide high-throughput approach to identify diagnostic and prognostic signatures that will refine tumor stratification and guide therapeutic options.One hundred CPTs were obtained from a multi-institutional tissue and clinical database. Copy-number (CN), DNA methylation, and gene expression signatures were assessed for 74, 36, and 40 samples, respectively. Molecular subgroups were correlated with clinical parameters and outcomes.Unique molecular signatures distinguished choroid plexus carcinomas (CPC) from choroid plexus papillomas (CPP) and atypical choroid plexus papillomas (aCPP); however, no significantly distinct molecular alterations between CPPs and aCPPs were observed. Allele-specific CN analysis of CPCs revealed two novel subgroups according to DNA content: hypodiploid and hyperdiploid CPCs. Hyperdiploid CPCs exhibited recurrent acquired uniparental disomy events. Somatic mutations in TP53 were observed in 60% of CPCs. Investigating the number of mutated copies of p53 per sample revealed a high-risk group of patients with CPC carrying two copies of mutant p53, who exhibited poor 5-year event-free (EFS) and overall survival (OS) compared with patients with CPC carrying one copy of mutant p53 (OS: 14.3%, 95% confidence interval, 0.71%-46.5% vs. 66.7%, 28.2%-87.8%, respectively, P = 0.04; EFS: 0% vs. 44.4%, 13.6%-71.9%, respectively, P = 0.03). CPPs and aCPPs exhibited favorable survival.Our data demonstrate that differences in CN, gene expression, and DNA methylation signatures distinguish CPCs from CPPs and aCPPs; however, molecular similarities among the papillomas suggest that these two histologic subgroups are indeed a single molecular entity. A greater number of copies of mutated TP53 were significantly associated to increased tumor aggressiveness and a worse survival outcome in CPCs. Collectively, these findings will facilitate stratified approaches to the clinical management of CPTs.
SIMPLE DEVICE FOR PRACTICING VASCULAR ANASTOMOSIS
Authors: Kent L. Brown
Journal: JAMA (1960)

Every surgeon should be able to anastomose or repair blood vessels. This knowledge is essential, since he may be called on at any time to perform such a procedure. Restoration of continuity of a blood vessel may enable him to save a limb or avert some other catastrophe. The techniques should be within the capability of any surgeon. The methods, though not difficult, require a knowledge of the use of the instruments used in vascular surgery and actual practice in doing anastomoses or repairs. In the event that specialized instruments are not available when needed, the surgeon who has learned and practiced the techniques with the instruments ordinarily used in vascular surgery should be able to substitute other instruments or materials. It is essential to have proper suture material, preferably 00000 or 000000, nonabsorbable suture, with a swedged-on curved needle. An arterial silk which meets these requirements is available. Physicians
Initiation of Plasma-Cell Differentiation Is Independent of the Transcription Factor Blimp-1
Authors: Axel Kallies, Jhagvaral Hasbold, Kirsten Fairfax, Clare Pridans, Dianne Emslie, Brent S. McKenzie, Andrew M. Lew, Lynn M. Corcoran, Philip D. Hodgkin, David M. Tarlinton, Stephen L. Nutt
Journal: Immunity (2007)
Long-Term Follow-Up of Patients Undergoing Balloon Dilation for Benign Pyloric Stenoses
Authors: S. P. Misra, M. Dwivedi
Journal: Endoscopy (1996)

Balloon dilation is a useful alternative to surgery in patients with benign pyloric stenoses. However, little data are available on the long-term outcome of the procedure.Fourteen patients with benign pyloric stenoses were treated by through-the-scope balloon dilation. Short-term and long-term follow-up was conducted (median 27 months).Balloon dilation was successfully performed in 12 patients (86%), and all 12 had immediate relief of symptoms after a single session. During a median follow-up of 27 months, 50% of the patients had recurrences of their symptoms, requiring redilation. Following this, two patients became symptomatic once again; one underwent surgery, and the other received a further session of balloon dilation, and was well at a further follow-up after one year.Balloon dilation of benign pyloric stenoses results in short-term symptomatic relief in the majority of patients. However, in the long-run, about half of the patients can be expected to experience a recurrence of symptoms, requiring further endoscopic or surgical treatment.
Familial apolipoprotein AI and apolipoprotein CIII deficiency. Subclass distribution, composition, and morphology of lipoproteins in a disorder associated with premature atherosclerosis.
Authors: T M Forte, A V Nichols, R M Krauss, R A Norum
Journal: Journal of Clinical Investigation (1984)

Lipoprotein classes isolated from the plasma of two patients with apolipoprotein AI (apo AI) and apolipoprotein CIII (apo CIII) deficiency were characterized and compared with those of healthy, age- and sex-matched controls. The plasma triglyceride values for patients 1 and 2 were 31 and 51 mg/dl, respectively, and their cholesterol values were 130 and 122 mg/dl, respectively; the patients, however, had no measurable high density lipoprotein (HDL)-cholesterol. Analytic ultracentrifugation showed that patients' S degrees f 0-20 lipoproteins possess a single peak with S degrees f rates of 7.4 and 7.6 for patients 1 and 2, respectively, which is similar to that of the controls. The concentration of low density lipoprotein (LDL) (S degrees f 0-12) particles, although within normal range (331 and 343 mg/dl for patients 1 and 2, respectively), was 35% greater than that of controls. Intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) (S degrees f 20-400) were extremely low in the patients. HDL in the patients had a calculated mass of 15.4 and 11.8 mg/dl for patients 1 and 2, respectively. No HDL could be detected by analytic ultracentrifugation, but polyacrylamide gradient gel electrophoresis (gge) revealed that patients possessed two major HDL subclasses: (HDL2b)gge at 11.0 nm and (HDL3b)gge at 7.8 nm. The major peak in the controls, (HDL3a)gge, was lacking in the patients. Gradient gel analysis of LDL indicated that patients' LDL possessed two peaks: a major one at 27 nm and a minor one at 26 nm. The electron microscopic structure of patients' lipoprotein fractions was indistinguishable from controls. Patients' HDL were spherical and contained a cholesteryl ester core, which suggests that lecithin/cholesterol acyltransferase was functional in the absence of apo AI. The effects of postprandial lipemia (100-g fat meal) were studied in patient 1. The major changes were the appearance of a 33-nm particle in the LDL density region of 1.036-1.041 g/ml and the presence of discoidal particles (12% of total particles) in the HDL region. The latter suggests that transformation of discs to spheres may be delayed in the patient. The simultaneous deficiency of apo AI and apo CIII suggests a dual defect in lipoprotein metabolism: one in triglyceride-rich lipoproteins and the other in HDL. The absence of apo CIII may result in accelerated catabolism of triglyceride-rich particles and an increased rate of LDL formation. Additionally, absence of apo CIII would favor rapid uptake of apo E-containing remnants by liver and peripheral cells. Excess cellular cholesterol would not be removed by the reverse cholesterol transport mechanism since HDL levels are exceedingly low and thus premature atherosclerosis occurs.
Ectopic Pregnancy in Relation to Previous Induced Abortion
Authors: Janet R. Daling, Wong Ho Chow, Noel S. Weiss, Barbara J. Metch, Richard Soderstrom
Journal: JAMA (1985)

Women who were hospitalized for ectopic pregnancy in five hospitals in King County, Washington, were interviewed concerning history of induced abortion. For comparison, women who delivered a live-born child during this same time period were also interviewed. Relative to women who had never undergone an abortion, the risk in those who had was increased to a modest degree, but this increase could well have been the result of chance (relative risk, 1.4; 95% confidence interval, 0.7 to 2.6). For women who had two or more abortions, the relative risk was 1.8 (95% confidence interval, 0.5 to 7.1). Our results suggest that legal abortion as performed during the past decade in the United States does not carry a large excess risk for future ectopic pregnancy, but larger studies will be needed in order to determine more precisely the magnitude of any excess that does exist.
Expression of p18INK4C is Down-regulated in Human Pituitary Adenomas
Authors: Md. Golam Hossain, Takeo Iwata, Noriko Mizusawa, Zhi Rong Qian, Shahidan Wan Nazatul Shima, Toru Okutsu, Shozo Yamada, Toshiaki Sano, Katsuhiko Yoshimoto
Journal: Endocrine Pathology (2009)
Mianserin Differentiated From Tricyclic Antidepressants
Authors: F. H. J. Jansen
Journal: JAMA (1978)

To the Editor.—  The article Cardiovascular Effects of Tricyclic and Tetracyclic Antidepressants by Burckhardt et al (239:213, 1978) is a condensed version of a report that appeared previously in theSchweizerische Medizinische Wochenschrift,1where it received valid criticism.2The conclusions reached are inaccurate and misleading, since the authors do not distinguish between preparations and consider them as congeners of one group of tricyclic or tetracyclic antidepressants. For maprotiline this is understandable, since this compound is, in fact, closely similar chemically, pharmacologically, and in clinical effect to the tricyclic antidepressants.3To classify maprotiline together with mianserin is a gross error when only four of 47 patients received mianserin. The latter compound is the first member of a chemically novel group of tetracyclic compounds unrelated to maprotiline.4Experimental studies in intact animals4and in isolated organs,5in healthy individuals,4and in patients with cardiac disease
Human Trachealis and Main Bronchi Smooth Muscle Are Normoresponsive in Asthma
Authors: Gijs Ijpma, Linda Kachmar, Oleg S. Matusovsky, Jason H. T. Bates, Andrea Benedetti, James G. Martin, Anne-Marie Lauzon
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Airway smooth muscle (ASM) plays a key role in airway hyperresponsiveness (AHR) but it is unclear whether its contractility is intrinsically changed in asthma.Objectives: To investigate whether key parameters of ASM contractility are altered in subjects with asthma.Methods: Human trachea and main bronchi were dissected free of epithelium and connective tissues and suspended in a force–length measurement set-up. After equilibration each tissue underwent a series of protocols to assess its methacholine dose–response relationship, shortening velocity, and response to length oscillations equivalent to tidal breathing and deep inspirations.Measurements and Main Results: Main bronchi and tracheal ASM were significantly hyposensitive in subjects with asthma compared with control subjects. Trachea and main bronchi did not show significant differences in reactivity to methacholine and unloaded tissue shortening velocity (Vmax) compared with control subjects. There were no significant differences in responses to deep inspiration, with or without superimposed tidal breathing oscillations. No significant correlations were found between age, body mass index, or sex and sensitivity, reactivity, or Vmax.Conclusions: Our data show that, in contrast to some animal models of AHR, human tracheal and main bronchial smooth muscle contractility is not increased in asthma. Specifically, our results indicate that it is highly unlikely that ASM half-maximum effective concentration (EC50) or Vmax contribute to AHR in asthma, but, because of high variability, we cannot conclude whether or not asthmatic ASM is hyperreactive.
Adaptation of hydrogen analysis to measure stomach to caecum transit time in the rat.
Authors: N J Brown, R D Rumsey, N W Read
Journal: Gut (1987)

Excreted hydrogen analysis was used to measure stomach to caecum transit time of the head of a test meal in 120 rats fed by gavage. Results were compared with the distribution of a labelled test meal in the gastrointestinal tract of rats killed at different time intervals after gavage. Values for stomach to caecum transit were compatible with the distribution of labelled meals in 91% of animals, although in the remainder the hydrogen concentration had not risen even though food residues were in the caecum when the animals were killed. The technique gave reproducible results; the coefficients of variation for four studies carried out in each of six animals varied between 4 and 14%. A meal consisting of homogenised baked beans had a significantly shorter stomach to caecum transit time (88.1 +/- 4.5 min; mean +/- SE; n = 21; p less than 0.001) than an equivalent volume of Complan/lactulose (180.9 +/- 8.7 min; n = 13). This technique was used to investigate the effect of ileal infusion of a fat emulsion (20% Intralipid) via a chronically implanted intestinal cannula on the stomach to caecum transit time of a bean meal, in a series of paired studies carried out in six rats. Stomach to caecum transit time was significantly delayed during ileal infusion of 20% Intralipid compared with the control infusion of an isotonic saline solution (218.3 +/- 21 min v 106.7 +/- 33 min Intralipid v saline; n = 6; p less than 0.001).
A Case of Talc Granuloma Simulating Carcinoma
Authors: F. Baar
Journal: BMJ (1953)

MEDICAL JOUs~RNAL been impossible.Nasal intubation under local analgesia does not seem to be unduly difficult in these circumstances.The precaution was taken not to give thiopentone until the respiratory obstruction was overcome.Davidson et al. (1949) have stated that the local swelling tends to diminish in 24 to 36 hours.The critical phase in our case lasted four days, and no deleterious effects seemed to result from intubating the trachea for that period of time.There is no doubt that the absence of chest complications was largely due to the post-operative nursing care and to the assiduous bronchial toilet.Summary A case of respiratory obstruction in a haemophilic patient is described.This complication was due to a spontaneous interstitial haemorrhage into the tongue and the floor of the mouth.Three other cases from the same hospital are cited.The management of the case reported consisted of blood transfusion, a submental incision, and nasotracheal intubation.It would seem that intubation presents certain advantages over, and may be preferable to, tracheotomy in the treatment of this medical emergency.A Magill naso- tracheal tube left in place for four days caused no obvious damage to the vocal cords.We wish to thank Dr. J. A. W. McCluskie and Mr. E. G. Gerstenberg, in whose wards the patient was treated, for per- mission to publish this case.
Osteosarcoma: Fifteen Years Later
Authors: Allen M. Goorin, Herbert T. Abelson, Emil Frei
Journal: New England Journal of Medicine (1985)

IN 1974, companion papers in the Journal discussed the improved disease-free survival among patients with osteosarcoma who had received adjuvant chemotherapy after surgery for the primary tumor. One of the papers described a regimen consisting of vincristine and high-dose methotrexate with leucovorin rescue1; the other discussed treatment with doxorubicin.2 The accompanying editorial praised the results of these two studies, and the earlier findings of Sutow et al.3 (who employed a four-drug combination regimen) by saying that they "not only represent a milestone in the treatment of this disease but also hold great promise for the future management of some . . .
Left Atrial Fibrosis and Recurrent Arrhythmia
Authors: Laurens F. Tops, Martin J. Schalij
Journal: JAMA (2014)

In the Delayed-Enhancement MRI Determinant of Successful Radiofrequency Catheter Ablation of Atrial Fibrillation (DECAAF) study, Dr Marrouche and colleagues1 demonstrated that assessment of left atrial fibrosis with delayed enhancement magnetic resonance imaging (MRI) was associated with the likelihood of recurrent arrhythmia after catheter ablation for atrial fibrillation (AF)
High-fructose diet preserves [beta ]-cell mass and prevents diabetes in nonobese diabetic mice: A potential role for increased insulin receptor substrate-2 expression
Authors: T. Orban, E. Landaker, Z. Ruan, T.P. Cordeman, R. Weitgasser, S. Bonner-Weir, R.A. Jackson, M.-E. Patti
Journal: Metabolism (2001)
Estradiol Accelerates Functional Endothelial Recovery After Arterial Injury
Authors: Kevin Krasinski, Ioakim Spyridopoulos, Takayuki Asahara, Rien van der Zee, Jeffrey M. Isner, Douglas W. Losordo
Journal: Circulation (1997)

The mechanisms of the established atheroprotective effects of estrogen have not been entirely clarified. Recent data suggest that agents that hasten the recovery of the endothelium after denuding injury will deter the development of neointimal lesions. Because estrogen has been shown to exert angiogenic effects in vitro and in vivo, we performed a series of experiments to evaluate whether estrogen was capable of accelerating reendothelialization.Ovariectomized Sprague-Dawley rats received estrogen replacement therapy in the form of subcutaneously implanted pellets designed to release 1.5 or 5.0 mg 17 beta-estradiol over 30 days. Deendothelializing balloon injury was performed 1 week after pellet implantation, and animals were euthanatized after 1 week for evaluation of reendothelialization (Evans blue staining) or 2 weeks for evaluation of reendothelialization and neointimal formation. At both time points, the use of estradiol caused a dose-dependent increase in reendothelialization, which was measured as absolute area and percentage of area that is reendothelialized. Estradiol accelerated functional endothelial recovery, manifested as an increase in nitric oxide production. Neointimal thickening was also shown to be inhibited in a dose-dependent fashion.Estrogen accelerates functional endothelial recovery after barotraumatic deendothelializing injury. These findings, along with the recent demonstration of estrogen receptor expression by endothelial cells, suggest that the antiatherogenic action of estrogen may be mediated in part through direct effects on endothelial cells.
Abstract 3660: Apigenin suppresses IKK activation and downstream signaling leading to prostate cancer inhibition.
Authors: Sanjeev Shukla, Manish Datt, Mark R. Chance, Sanjay Gupta
Journal: Cancer Research (2013)

Abstract Inhibitor of Nuclear Factor-κB kinase (IKK) complex is the master regulator of the NF-κB signaling pathway. IKK complex activation contributes to major cellular processes and plays a key role in the pathogenesis various human malignancies including prostate cancer. Recently, catalytic IKKs represent attractive targets for intervention with small molecule kinase inhibitors. We aimed to develop apigenin, a plant flavone, as a potent inhibitor of the IKK-kinase domain. IKK complex consist of structurally similar IKKα and IKKβ kinases. Both contains a kinase domain, a leucine-zipper motif through which the catalytic subunits dimerize, and a helix-loop-helix domain followed by a C-terminal tail that, when unphosphorylated interacts with IKKγ, the non-catalytic subunit. Screening of human prostate tumors demonstrated an increase in IKKα in low and high Gleason grade, whereas, IKKβ was higher in benign and low grade tumors. Phosphorylation of IKKα (Ser176/180) and IKKβ (Ser177/181) was significantly increased in prostate tumors compared to benign tissues. Treatment of human prostate cancer 22Rv1 and PC-3 cells to apigenin resulted in a decreased phosphorylation of IKKα/β in dose-dependent fashion, which correlated with lower proliferation and invasiveness. Ex Vivo IKK complex pull down assay using sepharose beads also confirmed direct binding of apigenin with IKK complex. In vivo studies with PC-3 and 22Rv1 xenografts in athymic nude mice further demonstrated that oral intake of apigenin at doses of 20 and 50μg/mouse/day over an 8-wk period resulted in a marked reduction in tumor growth, IKK activity, IKK phosphorylation, and NF-κB/p65 at both doses of apigenin. Furthermore, 3D structural in silico modeling analysis with PS1145, a known IKK inhibitor and apigenin were assessed for IKKα and IKKβ separately for protein-ligand docking studies using glide score. Apigenin was well anchored by hydrogen bonds with amino acid resides in the IKK complex protein at both ends. All three hydroxyl groups of apigenin were favorably oriented around different hydrogen bond acceptor atoms in the protein. Glide score generated by apigenin and PS1145 docking to IKK-α were -8.40 and -5.79, whereas IKK-β were -11.07 and -9.11; lower glide score represents better binding to IKK complex pocket. These results suggest that inhibition of cell proliferation and decrease in tumor growth by apigenin are mediated, at least in part, by its ability to suppress IKK complex and NF-κB signaling pathways. Citation Format: Sanjeev Shukla, Manish Datt, Mark R. Chance, Sanjay Gupta. Apigenin suppresses IKK activation and downstream signaling leading to prostate cancer inhibition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3660. doi:10.1158/1538-7445.AM2013-3660
POST-OPERATIVE INSANITY.
Authors: R. HARVEY REED
Journal: JAMA (1898)

For want of a better term I have adopted this one to indicate certain mental aberrations following operations. That very slight operations are not infrequently followed by severe attacks of insanity is beyond a question; at the same time the most severe operations on those who are insane are frequently followed by the return of their normal mental faculties. Why this unfortunate complication should follow certain operations in both male and female is a question which up to the present time has not been fully settled from a pathologic standpoint. Statistics on this important subject are severely wanting, and it is believed on the part of the writer, that notwithstanding a few cases of post-operative insanity have been reported from time to time in the journals, a great many more have not been reported, possibly for the want of knowledge as to their cause, or maybe a hesitancy on the
A Kindred With Hemoglobin Lepore
Authors: Robert A. O'Reilly
Journal: JAMA (1976)

Four members from three generations of a family of Italian descent were found to have hemoglobin (Hb) Lepore trait. The four affected members were only slightly anemic, yet had definite hypochromic and microcytic red blood cells (RBC). Electrophoresis of hemoglobin demonstrated an abnormal nonsickling hemoglobin of 11% to 14% concentration that migrated like Hb S at alkaline pH. Amino acid analysis confirmed the identity of the abnormal component as Hb Lepore; the non-α chain was a fused δ-β chain with a crossover between residues 87 and 116. Hemoglobin Lepore trait should be considered in any patient with clinical and laboratory findings consistent with β-thalassemia trait and with a 10% to 15% concentration of an abnormal nonsickling hemoglobin that migrates like Hb S. (<i>JAMA</i>236:478-480, 1976)