tbuckley/cabot-search huggingface dataset:
Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants.
Authors: T Yamaoka, C Idehara, M Yano, T Matsushita, T Yamada, S Ii, M Moritani, J Hata, H Sugino, S Noji, M Itakura
Journal: Journal of Clinical Investigation (1998)

Activin, a member of the TGF-beta superfamily, regulates the growth and differentiation of a variety of cell types. Based on the expression of activin in pancreatic rudiments of rat embryos and stimulation of insulin secretion from adult rat pancreatic islets by activin, activin is implicated in the development and function of islets. To examine the significance of activin signaling in the fetal and postnatal development of islets, transgenic mice expressing a dominant negative form of activin receptor (dn-ActR) or a constitutively active form of activin receptor (ActR-T206D) in islets were generated together with the transgenic mice expressing intact activin receptor (intact ActR) as a negative control. Transgenic mice with both dn-ActR and ActR-T206D showed lower survival rates, smaller islet area, and lower insulin content in the whole pancreas with impaired glucose tolerance when compared with transgenic mice with intact ActR or littermates, but they showed the same alpha cell/beta cell ratios as their littermates. In addition to islet hypoplasia, the insulin response to glucose was severely impaired in dn-ActR transgenic mice. It is suggested that a precisely regulated intensity of activin signaling is necessary for the normal development of islets at the stage before differentiation into alpha and beta cells, and that activin plays a role in the postnatal functional maturation of islet beta cells.
Adult Patient With Isolated Noncompaction of Ventricular Myocardium
Authors: Tomoya Kaneda, Masami Shimizu, Hidekazu Ino, Hidenobu Terai, Noboru Fujino, Katsuharu Uchiyama, Tomohito Mabuchi, Tetsuo Konno, Takashi Fujita, Eichi Masuda, Hiromasa Kato, Akira Funada, Hiroshi Mabuchi, Hiroko Ikeda
Journal: Circulation (2005)
Prevention of Oxaliplatin-Related Neurotoxicity by Calcium and Magnesium Infusions
Authors: Laurence Gamelin, Michele Boisdron-Celle, Remy Delva, Véronique Guérin-Meyer, Norbert Ifrah, Alain Morel, Erick Gamelin
Journal: Clinical Cancer Research (2004)

Oxaliplatin is active in colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. It may come from an effect on neuronal voltage-gated Na channels, via the liberation one its metabolite, oxalate. We decided to use Ca and Mg as oxalate chelators.A retrospective cohort of 161 patients treated with oxaliplatin + 5-fluorouracil and leucovorin for advanced colorectal cancer, with three regimens of oxaliplatin (85 mg/m(2)/2w, 100/2w, 130/3w) was identified. Ninety-six patients received infusions of Ca gluconate and Mg sulfate (1 g) before and after oxaliplatin (Ca/Mg group) and 65 did not.Only 4% of patients withdrew for neurotoxicity in the Ca/Mg group versus 31% in the control group (P = 0.000003). The tumor response rate was similar in both groups. The percentage of patients with grade 3 distal paresthesia was lower in Ca/Mg group (7 versus 26%, P = 0.001). Acute symptoms such as distal and lingual paresthesia were much less frequent and severe (P = 10(-7)), and pseudolaryngospasm was never reported in Ca/Mg group. At the end of the treatment, 20% of patients in Ca/Mg group had neuropathy versus 45% (P = 0.003). Patients with grade 2 and 3 at the end of the treatment in the 85 mg/m(2) oxaliplatin group recovered significantly more rapidly from neuropathy than patients without Ca/Mg.Ca/Mg infusions seem to reduce incidence and intensity of acute oxaliplatin-induced symptoms and might delay cumulative neuropathy, especially in 85 mg/m(2) oxaliplatin dosage.
Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007
Authors: A. Skiada, L. Pagano, A. Groll, S. Zimmerli, B. Dupont, K. Lagrou, C. Lass-Florl, E. Bouza, N. Klimko, P. Gaustad, M. Richardson, P. Hamal, M. Akova, J.F. Meis, J.-L. Rodriguez-Tudela, E. Roilides, A. Mitrousia-Ziouva, G. Petrikkos
Journal: Clinical Microbiology and Infection (2011)
Atherogenic role of lysophosphatidylcholine in low-density lipoprotein modified by phospholipase A2 and in diabetic patients: Protection by nitric oxide donor
Authors: Kazuo Sonoki, Masanori Iwase, Kenzo Iino, Kojiro Ichikawa, Shigehiro Ohdo, Shun Higuchi, Mototaka Yoshinari, Mitsuo Iida
Journal: Metabolism (2003)
Improving Accrual of Older Persons to Cancer Treatment Trials: A Randomized Trial Comparing an Educational Intervention With Standard Information: CALGB 360001
Authors: Gretchen G. Kimmick, Bercedis L. Peterson, Alice B. Kornblith, Jeanne Mandelblatt, Jeffrey L. Johnson, Judith Wheeler, Robin Heinze, Harvey J. Cohen, Hyman B. Muss
Journal: Journal of Clinical Oncology (2005)

Purpose To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group–sponsored treatment trials. Methods Main member institutions of the Cancer and Leukemia Group B (CALGB) and its affiliates were randomly assigned to receive standard information (n = 73) or educational intervention (n = 53). Standard information included CALGB Web site access and periodic notification about existing trials. The geriatric educational intervention included standard information plus: (1) an educational seminar; (2) educational materials; (3) a list of available protocols for use on charts; (4) a monthly e-mail and mail reminders for 1 year; and (5) a case discussion seminar. The main outcome was percentage of accrual of older persons to phase II and III treatment protocols after study initiation compared with baseline. Results There were 3,032 patients entered onto trials in the baseline year, and 2,160 and 1,239 during the 2 years postintervention, respectively. Overall percentage of accrual of older patients was 37% at baseline, and 33% and 31% during the first and second years after intervention. There was no improvement in accrual in the intervention versus control arm: 36% v 32% in the first year and 31% v 31% in the second year. Conclusion Accrual of older patients was not increased by this intervention. Reasons for lack of effect include low intervention intensity, high baseline accrual rates, and closure of several high-accruing protocols during the study. More intense and multifaceted approaches will be needed to change physician (and patient) behavior and to increase accrual of older persons to clinical trials.
Differential distribution and regulation of mouse cardiac Na+/K+-ATPase α1 and α2 subunits in T-tubule and surface sarcolemmal membranes
Authors: R BERRY, S DESPA, W FULLER, D BERS, M SHATTOCK
Journal: Cardiovascular Research (2006)

Two Na+/K+-ATPase (NKA) alpha-subunit isoforms, alpha1 and alpha2, are expressed in the adult mouse heart. The subcellular distribution of these isoforms in T-tubule and surface sarcolemmal (SSL) membranes and their regulation by cAMP-dependent protein kinase (PKA) is unclear.We used formamide-induced detubulation of mouse ventricular myocytes to investigate differential functional distribution and regulation by PKA of alpha1 and alpha2 in T-tubule versus SSL membranes by measuring NKA current (I(pump)) and NKA-mediated Na+ efflux (-d[Na](i)/dt).I(pump) is composed of 88% alpha(1)-mediated I(pump) (Ialpha1) and 12% alpha2-mediated I(pump) (Ialpha2). alpha1 and alpha2 subunits demonstrate distinct ouabain affinities (105+/-6 and 0.3+/-0.1 micromol/L respectively) but similar affinity for intracellular Na+ (K(1/2)Na+ of 16.6+/-0.8 and 16.7+/-2.6 mmol/L respectively). Detubulation reduced (i) I(pump) density (1.42+/-0.1 to 1.20+/-0.04 pA/pF), (ii) cell capacitance (181+/-12 to 127+/-17 pF), and (iii) Ialpha2 contribution (12 to 6%). Total I(pump) density was approximately 60% higher in T-tubule (1.94 pA/pF, derived) vs. SSL membranes. Although T-tubule membranes represent only 30% of total surface area, they generate approximately 70% of Ialpha2 and approximately 37% of Ialpha1. Ialpha1 density was substantially higher than Ialpha2 in SSL (Ialpha1:Ialpha2 = 16:1) but this was markedly reduced in T-tubules (4:1). In addition to differential localisation, isoprenaline (ISO, 1 micromol/L) significantly increased alpha1-mediated NKA Na+ affinity (from 16.6+/-0.8 to 13.3+/-1.4 mmol/L) and caused a small increase in maximal NKA Na+ efflux rate. ISO had no effect on alpha2-mediated NKA activity.These data suggest that NKA alpha1 and alpha2 subunits are differentially localised and regulated by PKA in T-tubule and SSL membranes and may have distinct regulatory roles in cardiac excitation-contraction coupling.
Risk stratification in pulmonary embolism: an algorithmic tool approach
Authors: N. Ahmad, K. Srinivasan, H. Moudgil
Journal: Thorax (2011)

in ventilationeperfusion heterogeneity, as seen in patients treated with a high dose of intravenous epoprostenol in whom IPS and severe hypoxaemia occurred. 5In these cases, an accurate diagnosis and drug down-titration or discontinuation allowed a rapid recovery of the symptoms.In conclusion, sildenafil may be associated with development of IPS and hypoxaemia in PAH patients.In these cases, an SC-TTE should be performed in order to disclose previously undiagnosed IPS.
BONE-MARROW TRANSPLANTATION IN HIGH-RISK ACUTE LYMPHOBLASTIC LEUKAEMIA IN FIRST AND SECOND REMISSION
Authors: RogerH. Herzig, A. John Barrett, Eliane Gluckman, StevenJ. Jacobsen, Tohru Masaoka, NormaK.C. Ramsay, Olle Ringden, FerdinandE. Zwaan, MortimerM. Bortin, KarlG. Blume, MaryM. Horowitz, Alberto Marmont, H. Grant Prentice, AlfredA. Rimm, Bruno Speck, Robert Peter Gale
Journal: The Lancet (1987)
Formal oxygen assessment; improving patient safety and reducing cost
Authors: Katherine Ibison, Nick John, Koothali Srinivasan, Harmesh Modgil
Journal: European Respiratory Journal (2012)

Introduction: Home oxygen prescribing in the UK has improved significantly, but it can still be ordered without the need for formal oxygen testing.

Results: Data were analyzed from 134 consecutive patients attending formal oxygen assessment at the Princess Royal Hospital, Telford. The patient's primary diagnoses are shown in Figure 1. They had a mean age of 72.2 (range 42-91) and 75% were on one or more modalities of oxygen prior to formal assessment (38% short burst, 53% ambulatory, 47% long term). The oxygen was prescribed mainly by Respiratory Nurses (40%) and General Practitioners (31%).

![Figure][1] 



A pO2 of ≤8kPa was found in 89% of patients with oxygen saturations of ≤92%. However, only 2% with saturations above 92%, had a pO2 of ≤8kPa. A clinically significant (≥4%) desaturation was seen in 15 out of 16 patients during ambulatory oxygen assessment. The outcome following the formal oxygen assessment is shown in Figure 2.

![Figure][1] 



Conclusions: Reassessment of patients already on oxygen is worthwhile and may improve patient safety and cost-eficiency. Oxygen saturations of ≤92% should be used to screen patients being considered for oxygen assessment. Ambulatory assessment is under-utilized.

 [1]: pending:yes
Superoxide Anion From the Adventitia of the Rat Thoracic Aorta Inactivates Nitric Oxide
Authors: Hui Di Wang, Patrick J. Pagano, Yue Du, Antonio J. Cayatte, Mark T. Quinn, Peter Brecher, Richard A. Cohen
Journal: Circulation Research (1998)

The purpose of this study was to determine whether superoxide anion is produced endogenously in the rat aortic adventitia and whether sufficient superoxide anion is produced to interfere with the response of the rat aorta to nitric oxide. Relaxation was measured in rings of the rat thoracic aorta, which were oriented so that the adventitial or luminal surface could be preferentially exposed to nitric oxide or sodium nitroprusside. To accomplish this, the rings were mounted (1) with the adventitia facing outward, (2) with the adventitia facing inward after inverting, or (3) with the adventitia facing outward after inverting twice (to control for the inverting procedure). The relaxation to nitric oxide, but not to sodium nitroprusside, was less in rings with the adventitia facing outward compared with those in which it faced inward. In contrast, the response to nitric oxide via either surface was similar when extracellular superoxide anion was scavenged with superoxide dismutase. Incubation of rings with nitro blue tetrazolium (NBT) resulted in blue formazan staining of the adventitia, and lucigenin chemiluminescence was significantly greater when detected from the adventitial compared with the intimal aspect of the artery. The reduction of NBT in intact aortic rings was 30+/-2 pmol x min(-1) x mg(-1) and was significantly decreased by superoxide dismutase to 19+/-2 pmol x min(-1) x mg(-1) and by a synthetic superoxide dismutase mimic, Euk-8, to 11+/-2 pmol x min(-1) x mg(-1). The NADPH oxidase inhibitor, diphenyleneiodonium, decreased NBT reduction to 9+/-1 pmol x min(-1) x mg(-1), whereas inhibitors of xanthine oxidase, mitochondrial oxidases, and nitric oxide synthase were ineffective. Immunohistochemical staining indicated the localization of NADPH oxidase proteins gp91phox, p22phox, p47phox, and p67phox almost exclusively in the adventitia of the rat aorta with no substantial staining in the media. These results indicate that NADPH oxidase located in the adventitia of rat thoracic aorta generates sufficient extracellular superoxide anion to constitute a barrier capable of inactivating nitric oxide. This study suggests that adventitial superoxide anion can play a role in the pathophysiology of the arterial wall.
Management of the Clinically Inapparent Adrenal Mass (“Incidentaloma”)
Authors: Melvin M. Grumbach
Journal: Annals of Internal Medicine (2003)

The National Institutes of Health Consensus Development Program convened surgeons, endocrinologists, pathologists, biostatisticians, radiologists, oncologists, and other health care professionals, as well as members of the general public, to address the causes, prevalence, and natural history of clinically inapparent adrenal masses, or incidentalomas; the appropriate evaluation and treatment of such masses; and directions for future research. Improvements in abdominal imaging techniques have increased detection of adrenal incidentalomas, and because the prevalence of these masses increases with age, appropriate management of adrenal tumors will be a growing challenge in our aging society. To address six predetermined questions, the 12-member nonfederal, nonadvocate state-of-the-science panel heard presentations from 21 experts in adrenal incidentalomas and consulted a systematic review of medical literature on the topic provided by the Agency for Healthcare Research and Quality and an extensive bibliography developed by the National Library of Medicine. The panel recommended a 1-mg dexamethasone suppression test and measurement of plasma-free metanephrines for all patients with an adrenal incidentaloma; additional measurement of serum potassium and plasma aldosterone concentrationplasma renin activity ratio for patients with hypertension; and surgery for patients with biochemical evidence of pheochromocytoma, patients with tumors greater than 6 cm, and patients with tumors greater than 4 cm who also meet other criteria. The panel also advocated a multidisciplinary approach to managing adrenal incidentalomas. The statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the federal government.
Enhanced Eosinophilic Inflammation and Airway Hyperresponsiveness in response to TLR3 Ligand in Murine Models of Asthma
Authors: K ASANO, Y SHIRAISHI, S KAGAWA, T TAKIHARA, S UEDA, M KODAMA, N HORIUCHI, K FUKUNAGA, T OGUMA, K SAYAMA
Journal: Journal of Allergy and Clinical Immunology (2008)
Wnt4/β-Catenin Signaling Induces VSMC Proliferation and Is Associated With Intimal Thickening
Authors: Aikaterini Tsaousi, Helen Williams, Cressida A. Lyon, Victoria Taylor, Amanda Swain, Jason L. Johnson, Sarah J. George
Journal: Circulation Research (2010)

Vascular smooth muscle cell (VSMC) proliferation causes intimal thickening in atherosclerosis and restenosis. Previously, we demonstrated that Wnt/β-catenin signaling upregulates VSMC proliferation in vitro.We examined this pathway in vivo and investigated the involvement of specific Wnt proteins in VSMC proliferation.Left carotid arteries of TOPgal (β-catenin signaling reporter) transgenic mice were ligated to induce intimal thickening. β-Catenin signaling was induced in the media and intima at 3 and 28 days after ligation, respectively, and was associated with VSMC proliferation and cyclin D1 expression. In vitro, a Wnt agonist promoted mouse VSMC proliferation, whereas Wnt inhibitory factor (WIF)-1 retarded platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation. Microarray analysis and quantitative PCR detected a significant induction of Wnt2 and Wnt4 mRNA in PDGF-BB-treated (proliferating) VSMCs compared to quiescent VSMCs. Western blotting revealed this increase was only translated into protein for Wnt4. Specific silencing RNA knockdown of Wnt4, but not Wnt2, significantly reduced VSMC proliferation. Recombinant Wnt4, but not Wnt2, significantly increased VSMC proliferation by ≈2-fold and silencing RNA knockdown revealed this is via Frizzled 1. Immunohistochemistry showed that increased Wnt4 protein correlated with VSMC proliferation and cyclin D1 expression (P<0.05 and P<0.001, respectively) during intimal thickening after rat carotid artery injury. Importantly, we also showed that intimal thickening and VSMC proliferation after carotid artery ligation was significantly retarded in Wnt4(+/-) compared to Wnt4(+/+) mice.This study demonstrates that Wnt/β-catenin signaling occurs in proliferating VSMCs during intimal thickening and indicates that this is a result of Wnt4 upregulation.
Restrictions Limiting the Generation of DNA Double Strand Breaks during Chromosomal V(D)J Recombination
Authors: Robert E. Tillman, Andrea L. Wooley, Maureen M. Hughes, Tara D. Wehrly, Wojciech Swat, Barry P. Sleckman
Journal: The Journal of Experimental Medicine (2002)

Antigen receptor loci are composed of numerous variable (V), diversity (D), and joining (J) gene segments, each flanked by recombination signal sequences (RSSs). The V(D)J recombination reaction proceeds through RSS recognition and DNA cleavage steps making it possible for multiple DNA double strand breaks (DSBs) to be introduced at a single locus. Here we use ligation-mediated PCR to analyze DNA cleavage intermediates in thymocytes from mice with targeted RSS mutations at the endogenous TCRβ locus. We show that DNA cleavage does not occur at individual RSSs but rather must be coordinated between RSS pairs flanking gene segments that ultimately form coding joins. Coordination of the DNA cleavage step occurs over great distances in the chromosome and favors intra- over interchromosomal recombination. Furthermore, through several restrictions imposed on the generation of both nonpaired and paired DNA DSBs, this requirement promotes antigen receptor gene integrity and genomic stability in developing lymphocytes undergoing V(D)J recombination.
Local IFN- responses in TB
Authors: R A M Breen
Journal: Thorax (2005)

Globally, the tuberculin skin test (TST), smear microscopy, and culture remain central to the diagnosis of tuberculosis (TB) because of the cost and ease of performance. However, TST has poor specificity and reduced sensitivity in settings including HIV and advanced TB,1 smear microscopy lacks sensitivity, and TB culture (the diagnostic gold standard) takes weeks and is positive in only two thirds of treated cases.2 TB pleuritis and peritonitis can be particularly difficult to diagnose due to paucity of bacilli and often need invasive or open procedures. In this setting, assays measuring interferon γ (IFN-γ) production by lymphocytes in response to TB antigens may be useful. While most studies have used blood based assays, more clinically relevant information may exist in local fluids such as bronchoalveolar lavage (BAL) fluid and pleural fluid in which much higher responses have been achieved.3–5

We investigated a 32 year old Somali man, resident in Britain for 2 years, who presented with a 3 week history of vomiting, diarrhoea, anorexia, and abdominal pain. …
Lubrication of synovial membrane.
Authors: A F Cooke, D Dowson, V Wright
Journal: Annals of the Rheumatic Diseases (1976)

(1) An apparatus has been constructed to measure the coefficient of friction of synovial membrane against a glass slider. (2) Provision was made to vary the load on the specimens. (3) The coefficient of friction varied from 0-006 to 0-07. (4) A presentation similar to that used in the Sommerfeld analysis of journal bearings indicated that in these experiments synovial membrane was lubricated in the hydrodynamic regimen.
THREE CASES TREATED BY THE "X" RAYS
Authors: F. O. Stedman
Journal: BMJ (1903)

encouraged by some statements in the last of the Erasmus Wilson lectures on Adenoma and Adeno-carcinoma of the Rectum, by Sir Charles Ball.The third lecture, which dealt with treatment, was published in the BRITISH MEDICAL JOURNAL of March 7th, 1903, a little more than a week after the operation I have described was actually done.In this lecture Sir Charles Ball strongly supports the " ab- dominal excision."He says this can be completed by bringing the sigmoid to the anus if the sigmoid mesocolon at its greatest length is 6 in.If decidedly less than this, he thinks the operation should be terminated by the formation of an inguinal anus.His method differs from that I have described in this important particular-namely, that he divides the bowel after tying it above and, if possible, below the growth, from the abdomen, and only then turns to the perineum, which would seem to give greater risk of soiling the peritoneum, though doubtless this can be obviated to a large extent by careful use of gauze wraps and pads.The fact that so great an authority on rectal disease states -that "many cases which have been treated by trans-sacral e2xcision would in his opinion have given a better result by this (abdominal) method" encourages me to hope that the -eperation I have described may prove a useful one.
Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma
Authors: Scott P. Commins, Libby A. Kelly, Eva Rönmark, Hayley R. James, Shawna L. Pochan, Edward J. Peters, Bo Lundbäck, Lucy W. Nganga, Philip J. Cooper, Janelle M. Hoskins, Saju S. Eapen, Luis A. Matos, Dane C. McBride, Peter W. Heymann, Judith A. Woodfolk, Matthew S. Perzanowski, Thomas A. E. Platts-Mills
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens.Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131).Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001).These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.