tbuckley/cabot-search huggingface dataset:
Preselection Thymocytes Are More Sensitive to T Cell Receptor Stimulation Than Mature T Cells
Authors: Gayle M. Davey, Sonya L. Schober, Bart T. Endrizzi, Angela K. Dutcher, Stephen C. Jameson, Kristin A. Hogquist
Journal: The Journal of Experimental Medicine (1998)

During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide–major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self-peptide–MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide–MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide–MHC complexes.
Treatment of hemobilia-induced biliary obstruction by transpapillary gallbladder and common bile duct drainage using three biliary winged stents
Authors: J. Buscaglia, K. Parashette, P. Okolo
Journal: Endoscopy (2008)

A 43-year-old man with Caroli’s disease underwent a transjugular intrahepatic portosystemic shunt procedure, after which he developed marked hemobilia that was believed to be secondary to hepatic artery injury. He then developed acute cholangitis as a result of the increased pressure on the bile ducts from obstructing blood clots. Four separate endoscopic retrograde cholangiopancreatograms were performed to clear thrombus from his bile ducts and relieve the obstruction with conventional stent placement, but after dislodgment of the clots the hemobilia recurred each time, with reocclusion of the stent.
Microglia induce CD4 T lymphocyte final effector function and death.
Authors: A L Ford, E Foulcher, F A Lemckert, J D Sedgwick
Journal: The Journal of Experimental Medicine (1996)

Microglia, a type of tissue macrophage, are the only cells in the central nervous system (CNS) parenchyma to express some major histocompatibility complex (MHC) class II constitutively or to upregulate expression readily. They are thought to play a role in CD4 T cell activation in autoimmune diseases such as multiple sclerosis, as well as in neurodegenerative conditions, Alzheimer's disease in particular. We show here that highly purified MHC class II+ microglia when tested directly ex vivo do indeed support an effector response by an encephalitogenic myelin basic protein-reactive CD4 T cell line from which production of the proinflammatory cytokines, interferon gamma and tumor necrosis factor, is elicited, but not interleukin (IL)-2 secretion or proliferation. After this interaction, the T cells die by apoptosis. Other nonmicroglial but CNS-associated macrophages isolated in parallel stimulate full T cell activation, including IL-2 production, proliferation, and support T cell survival. Neither CNS-derived population expresses B7.1/B7.2. Resident macrophages that terminate effector T cells in tissues constitute a novel and broadly applicable regulatory measure of particular relevance to processes of self-tolerance against sequestered antigens.
Detection of Human Polyomavirus 7 in Human Thymic Epithelial Tumors
Authors: Dorit Rennspiess, Sreedhar Pujari, Marlies Keijzers, Myrurgia A. Abdul-Hamid, Monique Hochstenbag, Anne-Marie Dingemans, Anna Kordelia Kurz, Ernst-Jan Speel, Anke Haugg, Diana V. Pastrana, Christopher B. Buck, Marc H. De Baets, Axel zur Hausen
Journal: Journal of Thoracic Oncology (2015)

Although the molecular genetics possibly underlying the pathogenesis of human thymoma have been extensively studied, its etiology remains poorly understood. Because murine polyomavirus consistently induces thymomas in mice, we assessed the presence of the novel human polyomavirus 7 (HPyV7) in human thymic epithelial tumors.HPyV7-DNA Fluorescence in situ hybridization (FISH), DNA-polymerase chain reaction (PCR), and immunohistochemistry (IHC) were performed in 37 thymomas. Of these, 26 were previously diagnosed with myasthenia gravis (MG). In addition, 20 thymic hyperplasias and 20 fetal thymic tissues were tested.HPyV7-FISH revealed specific nuclear hybridization signals within the neoplastic epithelial cells of 23 thymomas (62.2%). With some exceptions, the HPyV7-FISH data correlated with the HPyV7-DNA PCR. By IHC, large T antigen expression of HPyV7 was detected, and double staining confirmed its expression in the neoplastic epithelial cells. Eighteen of the 26 MG-positive and 7 of the 11 MG-negative thymomas were HPyV7-positive. Of the 20 hyperplastic thymi, 40% were HPyV7-positive by PCR as confirmed by FISH and IHC in the follicular lymphocytes. All 20 fetal thymi tested HPyV7-negative.The presence of HPyV7-DNA and large T antigen expression in the majority of thymomas possibly link HPyV7 to human thymomagenesis. Further investigations are needed to elucidate the possible associations of HPyV7 and MG.
Chronic hepatitis B virus infections is associated with mutations in the mannose binding protein gene
Authors: H THOMAS
Journal: Hepatology (1995)

A selective delivery of drugs to liver can be obtained by conjugation with galactosyl terminating macromolecules. The conjugates selectively enter hepatocytes after interaction of the carrier galactose residues with the asialoglycoprotein receptor (ASGP-R) present only on these cells. Within hepatocytes the conjugates are transported to lysosomes where the drug is set free from the carrier, becoming concentrated in liver cells. The present article reviews the liver targeting of drugs obtained with lactosaminated albumin (L-SA), a neoglycoprotein exposing galactosyl residues. We report: (1) experiments which demonstrate the antiviral efficacy of the L-H(human)SA-ara-AMP conjugate in laboratory animals and in humans with viral hepatitis; (2) the property of a L-HSA conjugate with fluorodeoxyuridine to produce concentrations of the drug higher in hepatic sinusoids than in systemic circulation, with the potential of accomplishing a loco-regional, noninvasive treatment of liver micrometastases; (3) the increased anticancer activity of doxorubicin (DOXO) when coupled to L-HSA on all the forms of chemically induced rat hepatocellular carcinomas including those which do not express the ASGP-R.
Chinese-Style Decentralization and Health System Reform
Authors: David Hipgrave, Sufang Guo, Yan Mu, Yan Guo, Fei Yan, Robert Scherpbier, Hana Brixi
Journal: PLoS Medicine (2012)

China’s health system reform (HSR) recently entered a second phase, the State Council and a multi-agency steering committee announced many important new initiatives. However, China’s social sectors are heavily decentralized, the Ministry of Health has limited influence on the detailed design and implementation of the HSR at sub-national level. Sub-national leaders in China are mostly driven by economic progress and revenue generation; health is generally regarded as consuming, not generating revenue. A new health management information system and performance-based management of health staff may enhance oversight. However, parallel reforms in governance, financing, and accountability are also needed in China, to ensure achievement of the equity objective of its HSR.
Abstract 2409: BCL10 regulates RNF8/RNF168-mediated ubiquitination in the DNA damage response
Authors: Hongchang Zhao, Min Zhu, Xingzhi Xu
Journal: Cancer Research (2014)

Abstract Our genome is constantly attacked by a variety of endogenous and environmental agents. Timely and properly cellular response to DNA damage is essential for maintenance of genome stability and integrity, which plays key roles in prevention of tumor initiation and development. B-cell lymphoma/leukemia 10 (BCL10), when translocated or mutated, contributes to mucosa-associated lymphoid tissue lymphomas and other malignancies. However, the mechanisms by which the resulting aberrant expression of BCL10 leads to tumorigenesis are poorly understood. In this report, we uncovered that, in response to DNA damage, BCL10 is recruited to the damage sites and modified sequentially by phosphorylation and ubiquitination. Modified BCL10 in turn facilitates to bring about cascades of ubiquitination and recruitment of DNA damage response (DDR) factors, promoting high-fidelity DNA repair. Furthermore, BCL10 is over-expressed in breast tumors (376 cases of breast cancer vs. 62 cases of normal breast, p=0.000). Taken together, our study reveals a novel function of BCL10 in ubiquitination-driven DDR, contributing to the maintenance of genome stability and integrity. Note: This abstract was not presented at the meeting. Citation Format: Hongchang Zhao, Min Zhu, Xingzhi Xu. BCL10 regulates RNF8/RNF168-mediated ubiquitination in the DNA damage response. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2409. doi:10.1158/1538-7445.AM2014-2409
Prehospital Brady-Asystolic Cardiac Arrest
Authors: LLOYD T. ISERI
Journal: Annals of Internal Medicine (1978)

Of 133 persons with spontaneous cardiac arrest attended by paramedics within 10 minutes, 100 (75%) had ventricular fibrillation as the initial rhythm and 33 (25%) had extreme bradycardia or asystole. The latter group of arrhythmias was characterized by sinus arrest or severe sinus bradycardia (90%) and complete A-V block (10%). Junctional escape rhythm was also absent or markedly retarded. Despite cardiopulmonary resuscitation and the administration of epinephrine, atropine, isoproterenol, and sodium bicarbonate, recovery of the sinus and junctional tissues was infrequent. Ventricular fibrillation developed in 11 cases (33%). One patient lived 12 days, but all others were dead on arrival or died in the emergency room. Among the 13 coronary causes of death proved at autopsy, 10 (77%) were due to a fresh thrombus and seven (54%) to an occluded proximal right coronary artery, suggesting a causal relation to this type of arrest.
Total insulin and IGF-I resistance in pancreatic β cells causes overt diabetes
Authors: Kohjiro Ueki, Terumasa Okada, Jiang Hu, Chong Wee Liew, Anke Assmann, Gabriella M Dahlgren, Jennifer L Peters, Jonathan G Shackman, Min Zhang, Isabella Artner, Leslie S Satin, Roland Stein, Martin Holzenberger, Robert T Kennedy, C Ronald Kahn, Rohit N Kulkarni
Journal: Nature Genetics (2006)
Spontaneous Hyperventilation Tetany
Authors: F. S. Fowweather, C. L. Davidson, L. Ellis
Journal: BMJ (1940)

Tetany as a sequel to overbreathing has been known for some time.The first observations appear to have been made by Haldane and Poulton (1908), who in experiments involving forced breathing noticed that the subjects of the experiments developed tingling in the hands and feet, and certain other symptoms.It was Grant and Goldman (1920), however, who first completely identified with tetany the condition following forced respiration.Shortly after- wards the occurrence of clinical cases of hyperventilation tetany was reported by Barker and Sprunt (1922) and by Goldman (1922).The causes of overbreathing which may give rise to tetany are numerous.They include certain cerebral con- ditions which presumably operate by some effect on the respiratory centre, exercise, pain, and nausea.The great majority of cases, however, have little or no recognizable organic background, but occur in those suffering from anxiety states, hysteria, or psychoneuroses, and the patients are for the most part young women.Diagnosis in most cases is not difficult ; there may be a history of disturbance of respiration, or increased rate or depth of respiration may be obvious on examination.Many authors stress the value of making the patient over- breathe and so inducing an attack.This is useful not only as a diagnostic procedure but also in demonstrating to him how, by voluntary effort to check overbreathing, he may ward off attacks.Kerr, Dalton, and Gliebe (1937), Rossier (1939), and others believe that not only typical tetany but many other clinical manifestations may be the
Follicular lymphoma: 2011 update on diagnosis and management
Authors: Arnold Freedman
Journal: American Journal of Hematology (2011)

Abstract Disease overview: Follicular lymphoma (FL) is generally an indolent B‐cell lymphoproliferative disorder of transformed follicular center B cells. FL is characterized by diffuse lymphoadenopathy, bone marrow involvement, splenomegaly, and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. Diagnosis: Diagnosis is based on histology of preferably biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10 and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl‐2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl‐2 genes. Risk stratification: The Follicular Lymphoma International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age &gt; 60 years, hemoglobin &lt;12 g/dL, serum LDH &gt; normal, Ann Arbor stage III/IV, number of involved nodal areas &gt; 4. The presence of 0–1, 2, and ≥3 adverse factors defines low, intermediate, and high‐risk disease with median 10 year survivals in the pre‐rituximab era of approximately 71, 51, and 36 months, respectively. With the use of more modern therapies, specifically anti‐CD20 monoclonal antibody, the outcome has improved. Risk‐adapted therapy: Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response, and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy‐rituximab and single agent rituximab. Autologous stem cell transplantation has not shown a survival benefit in first remission patients. Stem cell transplantation (SCT) including both autologous and allogeneic SCT or experimental agent therapy is considered for recurrent disease. Am. J. Hematol. 86:769‐775, 2011. © 2011 Wiley‐Liss, Inc.
Endoscopic-assisted Tube Placement for Decompression of Acute Colonic Pseudo-obstruction
Authors: J.M. Messmer, J.C. Wolper, C.J. Loewe
Journal: Endoscopy (1984)

A case of acute pseudo-obstruction of the colon is presented. Treatment consisted of placing a Bilbao-Dotter hypotonic duodenography tube in the transverse colon, threaded over an angiographic guidewire placed endoscopically. A discussion of acute pseudo-obstruction of the colon is given.
Review of Daniel P. Sulmasy,<i>The Rebirth of the Clinic: An Introduction to Spirituality in Healthcare</i>.<sup>1</sup>
Authors: Aaron Klink
Journal: The American Journal of Bioethics (2008)

1. Washington, D.C.: Georgetown, 2007. 246 pp. $24.95 paperback. In recent years the roles of “spirituality” and “religion” in health and medical practice have received much attention. Dozens of st...
Biliary excretion of estradiol-17 beta-glucuronide in the rat
Authors: H TAKIKAWA
Journal: Hepatology (1996)

Estradiol-17beta-glucuronide (E217G) is a cholestatic agent and is considered to be related to the pathogenesis of intrahepatic cholestasis of pregnancy. In the current study, we examined the mechanism of the biliary excretion of E217G and estradiol metabolites in rats. Biliary excretion of tracer doses of [3H]estradiol-17beta-glucuronide and [14C]estradiol or [3H]taurocholate and ]14C]vinblastine, a P-glycoprotein (P-GP) substrate, intravenously administered as a bolus to bile-drained control rats or EHBR was studied. Biliary excretion of E217G and estradiol metabolites EHBR was markedly delayed. Analyses of biliary metabolites after estradiol injection showed less polar conjugates in EHBR. In contrast, the excretion of taurocholate and vinblastine (VLB) was only slightly delayed in EHBR. Although phenothiazine treatment to induce the expression of P-GP increased biliary vinblastine excretion, it did not affect biliary excretion of a tracer dose of [3H]estradiol-17beta-glucuronide. However, phenothiazine treatment inhibited the cholestasis induced by E217G infused at the rate of 0.075 micromol/min/100g for 20 minutes and increased biliary E217G excretion. Sulfobromophthalein infusion (0.2 micromol/min/100 g body 0 weight) markedly inhibited the biliary excretion of E217G and estradiol metabolites, whereas dibromosulfophthalein (DBSP) at the same infusion rate had no effect. These findings indicate that EG17G is excreted into bile by a canalicular organic anion carrier for sulfobromopthalein (BSP), not for DBSP, under physiological conditions, and that P-GP influences E217G excretion only at a high dose. under physiological conditions, and that P-GP influence s E217G excretion only at a high dose.
Medicine and the Doctor in Word and Epigram
Authors: Sara M. Jordan
Journal: New England Journal of Medicine (1953)

THE honor that you have conferred upon me by electing me to this office carries with it an obligation that my predecessors have discharged with such a diversity of subjects as to allow free rein to my imagination. It seemed to me, therefore, a unique opportunity to revert to a premedical (now almost a prehistoric) interest of mine, philology, a love of words, and in its light, to scan the field of medicine. It was quite obvious from wordaand facial expression of the friends to whom I confided my plan that they thought very little of it, such questions as . . .
Prime minister proposes legal guarantees for patients to be treated within target times
Authors: Z. Kmietowicz
Journal: BMJ (2009)

Patients in England could be given the legal right to be treated privately if the NHS cannot provide the care they need within target times set by the government, the prime minister, Gordon Brown, has said.

Proposals for new patient rights in the NHS constitution will mean that from 1 April 2010 patients will have the legal right to start treatment by a consultant within 18 weeks of referral by their GP and to be seen by a cancer specialist within two weeks of referral. If the NHS is unable to meet these commitments it will have to find an alternative provider, which could include private providers, who would treat patients at NHS prices. …
The Kenyan Luo migration study: observations on the initiation of a rise in blood pressure.
Authors: N R Poulter, K T Khaw, B E Hopwood, M Mugambi, W S Peart, G Rose, P S Sever
Journal: BMJ (1990)

To demonstrate the magnitude, timing, and cause of changes in blood pressure that occur in migrants from a low blood pressure population on moving to an urban area.A controlled longitudinal observational study of migrants as soon after migration as possible and follow up at three, six, 12, 18, and 24 months after migration. A cohort of controls living in a rural area who were matched for age, sex, and locality were also observed at the same periods.35 Villages on the northern shores of Lake Victoria in western Kenya and Nairobi.325 Members of the Luo tribe aged 15 to 34 years who had migrated to Nairobi and 267 controls living in villages. The numbers of both groups reduced during follow up such that only 63 migrants and 143 controls were followed up for two years.A medical questionnaire and three 24 hour diet histories were completed by migrants and controls. Height, weight, pulse, and blood pressure were measured. Three 12 hour overnight urine samples were collected from all participants and analysed for sodium, potassium, and creatinine concentrations.The mean systolic blood pressure of migrants was significantly higher than that of controls throughout the study, and the distribution of blood pressure was shifted to the right compared with controls. The mean diastolic blood pressure of the two groups diverged over time. Blood pressure differences were not due to selective migration. The migrants' mean urinary sodium:potassium ratio was higher than that of controls (p less than 0.001) throughout, and weight and pulse rate were also higher among migrants, although differences diminished with time.Urinary sodium:potassium ratio, pulse rate, and weight are important predictors of increased blood pressure among migrants from a low blood pressure community and may also be implicated in the initiation of essential hypertension.
Normal and hypertrophic scars: quantification and localization of messenger RNAs for type I, III and VI collagens
Authors: L.-Q. ZHANG, M. LAATO, P. MUONA, H. KALIMO, J. PELTONEN
Journal: British Journal of Dermatology (1994)

The expression of type I, III and VI collagens was studied in nine normal and two hypertrophic scars using slot-blot and in situ hybridization techniques. Slot-blot hybridization indicated that the steady-state levels of proα 1(I) and proα 1(III) collagen chain mRNAs were moderately elevated in two of the nine normal scars, whereas the two hypertrophic scars analysed displayed markedly elevated mRNA levels when compared with normal skin. The mRNA levels of α2(VI) collagen chain were only slightly elevated in both types of scars studied. In situ hybridization was most informative when applied to hypertrophic scars. These lesions were characterized by the presence of intense hybridization signals for type I and III collagen mRNAs, and a moderate signal for type VI collagen mRNA, in nodules which were located in the upper dermis on each side of the original wound. This may explain, in part, why hypertrophic scars rise above the level of the surrounding skin. The results of the present study are in marked contrast to our previous findings on collagen gene expression in keloids and neurofibromas, in which the steady-state levels of type VI and I collagen mRNAs in particular were shown to be elevated. Thus, our results emphasize that distinct molecular mechanisms are operative in the development of clinically different dermal fibrotic conditions, such as normal and hypertrophic scars, keloids and neurofibromas.
New virus is identified in Malaysia epidemic
Authors: A. Easton
Journal: BMJ (1999)

Most of the cases, including 98 deaths, in the recent viral encephalitis outbreak in Malaysia have been due to contact with a newly identified virus, spread from pigs to humans, which government officials have named “nipah.” Thousands of pigs have been slaughtered in an attempt to combat the disease.

Initially, the Malaysian government believed the outbreak, which occurred in the pig farming states of Perak, Negri …
THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia
Authors: Pamela V Tran, Courtney J Haycraft, Tatiana Y Besschetnova, Annick Turbe-Doan, Rolf W Stottmann, Bruce J Herron, Allyson L Chesebro, Haiyan Qiu, Paul J Scherz, Jagesh V Shah, Bradley K Yoder, David R Beier
Journal: Nature Genetics (2008)