tbuckley/cabot-search huggingface dataset:
Rapamycin, but Not FK-506, Increases Endothelial Tissue Factor Expression
Authors: Jan Steffel, Roberto A. Latini, Alexander Akhmedov, Dorothee Zimmermann, Pamela Zimmerling, Thomas F. Lüscher, Felix C. Tanner
Journal: Circulation (2005)

Background— Drugs released from stents affect the biology of vascular cells. We examined the effect of rapamycin and FK-506 on tissue factor (TF) expression in human aortic endothelial cells (HAECs) and vascular smooth muscle cells (HAVSMCs). Methods and Results— Rapamycin enhanced thrombin- and tumor necrosis factor (TNF)-α–induced endothelial TF expression in a concentration-dependent manner. The maximal increase was 2.5-fold more pronounced than that by thrombin or TNF-α alone and was paralleled by a 1.4-fold higher TF surface activity compared with thrombin alone. Rapamycin by itself increased basal TF levels by 40%. In HAVSMCs, rapamycin did not affect thrombin- or TNF-α–induced TF expression. In contrast to rapamycin, FK-506 did not enhance thrombin- or TNF-α–induced endothelial TF expression. Thrombin induced a transient dephosphorylation of the mammalian target of rapamycin downstream target p70S6 kinase. Rapamycin completely abrogated p70S6 kinase phosphorylation, but FK-506 did not. FK-506 antagonized the effect of rapamycin on thrombin-induced TF expression. Rapamycin did not alter the pattern of p38, extracellular signal–regulated kinase, or c-Jun NH 2 -terminal kinase phosphorylation. Real-time polymerase chain reaction analysis revealed that rapamycin had no influence on thrombin-induced TF mRNA levels for up to 2 hours but led to an additional increase after 3 and 5 hours. Conclusions— Rapamycin, but not FK-506, enhances TF expression in HAECs but not in HAVSMCs. This effect requires binding to FK binding protein-12, is mediated through inhibition of the mammalian target of rapamycin, and partly occurs at the posttranscriptional level. These findings may be clinically relevant for patients receiving drug-eluting stents, particularly when antithrombotic drugs are withdrawn or ineffective, and may open novel perspectives for the design of such stents.
NOTE ON THE PRESENCE OF "BILHARZIA HAEMATOBIA" IN EGYPTIAN MUMMIES OF THE TWENTIETH DYNASTY [1250-1000 B.C.]
Authors: M. A. Ruffer
Journal: BMJ (1910)

In southern Brittany (France), the Porphyroid nappe, a Variscan tectonic unit made of volcanic pyroclastic deposits that was involved in a low-temperature/high-pressure prograde metamorphic path followed by exhumation and extension, displays evidence for very large and distributed strains achieved through dissolution/crystallization processes. Such distributed strains at low temperature are rather unusual in felsic lithologies. Recent studies have documented that these rocks deformed within a system closed to fluids. This paper presents results of detailed analyses of fluid inclusions and stable isotopes within the deformed metavolcanics and their undeformed counterparts in order to document the fluid history of the tectonic unit. Results show that its initial thermal evolution, likely occurring in a context of basin inversion, involved important open-system alteration, with K-metasomatism (adularization), oil impregnation and hydration. During the subsequent tectonic evolution, the fluids maintained a constant composition in the C-H-O-N system within the Porphyroid nappe and its para-autochthon, being water-rich and containing hydrocarbon components likely related to oil pyrolysis/oxidation. Atoll-like fluid inclusion morphology and rare undisturbed fluid inclusions with steep isochore slopes are consistent (&gt; 750 MPa) with pressures estimated for the peak of metamorphism using mineral solid-solution thermodynamics. Fluid inclusions indicate a sub-isothermal retrograde path (between 420 and 300°C) followed by a high thermal gradient at the end of the retrograde path. Within the underlying para-autochthonous unit, only the late, high-temperature gradient is recorded by fluid inclusions. The sub-isothermal low-grade path suggests fast exhumation of the unit, without thermal relaxation. The high geotherm observed at the end of the P-T path is consistent with the post-thickening extensional collapse and associated intrusion of granites documented in the area. Hydration and heterogeneous oil/water distribution achieved in the early metasomatic evolution of the porous pyroclastic deposits are responsible for subsequent fluid confining in the Porphyroid nappe and for its strongly distributed strain pattern.
Association of Maternal Diabetes With Autism in Offspring
Authors: Anny H. Xiang, Xinhui Wang, Mayra P. Martinez, Johanna C. Walthall, Edward S. Curry, Kathleen Page, Thomas A. Buchanan, Karen J. Coleman, Darios Getahun
Journal: JAMA (2015)

Information about the association of maternal diabetes and autism spectrum disorders (ASDs) in offspring is limited, with no report on the importance of timing of exposure during gestation.To assess ASD risk associated with intrauterine exposure to preexisting type 2 diabetes and gestational diabetes mellitus (GDM) by gestational age at GDM diagnosis.Retrospective longitudinal cohort study including 322 323 singleton children born in 1995-2009 at Kaiser Permanente Southern California (KPSC) hospitals. Children were tracked from birth until the first of the following: date of clinical diagnosis of ASD, last date of continuous KPSC health plan membership, death due to any cause, or December 31, 2012. Relative risks of ASD were estimated by hazard ratios (HRs) using Cox regression models adjusted for birth year.Maternal preexisting type 2 diabetes (n = 6496), GDM diagnosed at 26 weeks' gestation or earlier (n = 7456) or after 26 weeks' gestation (n = 17 579), or no diabetes (n = 290 792) during the index pregnancy.Clinical diagnosis of ASD in offspring.During follow-up, 3388 children were diagnosed as having ASD (115 exposed to preexisting type 2 diabetes, 130 exposed to GDM at ≤26 weeks, 180 exposed to GDM at >26 weeks, and 2963 unexposed). Unadjusted annual ASD incidences were 3.26, 3.02, 1.77, and 1.77 per 1000 among children of mothers with preexisting type 2 diabetes, GDM diagnosed at 26 weeks or earlier, GDM diagnosed after 26 weeks, and no diabetes, respectively. The birth year-adjusted HRs were 1.59 (95% CI, 1.29-1.95) for preexisting type 2 diabetes, 1.63 (95% CI, 1.35-1.97) for GDM diagnosed at 26 weeks or earlier, and 0.98 (95% CI, 0.84-1.15) for GDM diagnosed after 26 weeks relative to no exposure. After adjustment for maternal age, parity, education, household income, race/ethnicity, history of comorbidity, and sex of the child, maternal preexisting type 2 diabetes was not significantly associated with risk of ASD in offspring (HR, 1.21; 95% CI, 0.97-1.52), but GDM diagnosed at 26 weeks or earlier remained so (HR, 1.42; 95% CI, 1.15-1.74). Antidiabetic medication exposure was not independently associated with ASD risk. Adjustment for a mother or older sibling with ASD in the full cohort and for maternal smoking, prepregnancy body mass index, and gestational weight gain in the subset with available data (n = 68 512) did not affect the results.In this large, multiethnic clinical cohort of singleton children born at 28 to 44 weeks' gestation, exposure to maternal GDM diagnosed by 26 weeks' gestation was associated with risk of ASD in offspring.
1231 Soluble glypican-3 (SGPC3), identified by genome-wide analysis of gene-expression profiles using oligonucleotide microarray, is a candidate of biomarker for well to moderately differentiated hepatocellular carcinoma
Authors: K WATANABE, Y MIDORIKAWA, H KANAMORI, Y HIPPO, W AKIRA, S OHNISHI, T KODAMA, M MAKUUCHI, H ABURATANI
Journal: Hepatology (2003)

DNA microarray analysis of human cancer has resulted in considerable accumulation of global gene profiles. However, extraction and understanding the underlying biology of cancer progression remains a significant challenge. This study applied a novel integrative computational and analytical approach to this challenge in human hepatocellular carcinoma (HCC) with the aim of identifying potential molecular markers or novel therapeutic targets. We analysed 100 HCC tissue samples by human 30 K DNA microarray. The gene expression data were uploaded into the network analysis tool, and the biological networks were displayed graphically. We identified several activated ‘hotspot’ regions harbouring a concentration of upregulated genes. Several ‘hotspot’ regions revealed integrin and Akt/NF-κB signalling. We identified key members linked to these signalling pathways including osteopontin (SPP1), glypican-3 (GPC3), annexin 2 (ANXA2), S100A10 and vimentin (VIM). Our integrative approach should significantly enhance the power of microarray data in identifying novel potential targets in human cancer.
Scintigraphic Detection of Pulmonary Hemorrhage Using Tc-99m-Sulfur Colloid
Authors: GARY G. WINZELBERG, MARK H. WHOLEY
Journal: Clinical Nuclear Medicine (1981)

Pulmonary hemorrhage, whether in the form of hemoptysis or bleeding into the pleural space, may be a life threatening problem. While fiberoptic bronchoscopy and selective bronchial and intercostal angiography are the major diagnostic modalities, these techniques are not without risks. Two patients are described-one with massive hemoptysis from a bronchogenic carcinoma; another with pleural bleeding from a torn intercostal artery-in whom Tc-99m-sulfur colloid scintigraphy accurately located the source of hemorrhage. We conclude that Tc-99m-sulfur colloid scintigraphy may be a helpful noninvasive method to increase the sensitivity and specificity of fiberoptic bronchoscopy and bronchial angiography in patients with massive pulmonary bleeding.
Beyond Mortality
Authors: Roger G. Spragg, Gordon R. Bernard, William Checkley, J. Randall Curtis, Ognjen Gajic, Gordon Guyatt, Jesse Hall, Elliott Israel, Manu Jain, Dale M. Needham, Adrienne G. Randolph, Gordon D. Rubenfeld, David Schoenfeld, B. Taylor Thompson, Lorraine B. Ware, Duncan Young, Andrea L. Harabin
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Section:ChooseTop of pageAbstract <<DEFINITIONS AND STUDY INC...BIOMARKERS IN STUDIES OF ...OTHER VENTILATED PATIENTSQUALITY-OF-LIFE STUDIES O...CLINICAL STUDY ENDPOINTSPREVENTION TRIALSVALUE OF PHASE II STUDIES...TRIAL DESIGNPRIORITIZED RECOMMENDATIO...ReferencesCITING ARTICLES
A Doctor for the People: 2,000 Years of General Practice in Britain
Authors: Amasa B. Ford
Journal: JAMA (1981)

To compress 2,000 years of the history of a profession into 127 pages of text is a difficult task, even for an experienced teacher, and Dr Cule has made only a partial success of it. The approach he has taken is to write an informal narrative in an easy, almost conversational style, with ample color and black-and-white illustrations, which avoids textual footnotes and presents an eclectic mixture of social history, technical information, brief biographical references, and occasional interpretive comments. The result is a readable essay, authoritative in that the writer was himself a general practitioner for several years before turning to medical history, which he has taught in London and now teaches in Wales. Almost inevitably, large topics and stretches of history are passed over so summarily that the book can hardly escape the charge of superficiality. The British reader, for whom such terms as "the Tudor period" or "the
Tracheobronchial Foreign Bodies
Authors: Warren L. Whitlock
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 September 1990Tracheobronchial Foreign BodiesWarren L. Whitlock, MD, Christopher R. Brown, MD, Michael B. Young, MDWarren L. Whitlock, MDSearch for more papers by this author, Christopher R. Brown, MDSearch for more papers by this author, Michael B. Young, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-6-482_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: We disagree with Drs. Limper and Prakash (1) that rigid bronchoscopy is the instrument of choice in extracting tracheobronchial foreign bodies. Of their 60 patients, only 23 had had fiberoptic bronchoscopy for foreign body removal over 19 years, resulting in 1.2 cases per year. The position paper by the American Thoracic Society lists removal of foreign bodies as the second therapeutic use for fiberoptic bronchoscopy (2). Although adults do not commonly aspirate foreign bodies, we have successfully diagnosed and treated three adults in the last 2 years with fiberoptic bronchoscopy.We agree with the authors' grouping of...References1. LimperPrakash AU. Tracheobronchial foreign bodies in adults. Ann Intern Med. 1990;112:604-9. LinkGoogle Scholar2. SokolowskiBurgherJonesPattersonSelecky JLFJP. Guidelines for fiberoptic bronchoscopy in adults. Am Rev Respir Dis. 1987;136:1066. CrossrefMedlineGoogle Scholar3. RogersIgini LJ. Beverage can pull-tabs: inadvertent ingestion or aspiration. JAMA. 1975;233:345-8. CrossrefMedlineGoogle Scholar4. Zavala D. Complications following fiberoptic bronchoscopy. Chest. 1978;73:783-5. CrossrefMedlineGoogle Scholar1. LimperPrakash AU. Tracheobronchial foreign bodies in adults. Ann Intern Med. 1990;112:604-9. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Warren L. Whitlock, MD; Christopher R. Brown, MD; Michael B. Young, MDAffiliations: Letterman Army Medical Center Presidio of San Francisco, CA 94129-6700 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRetained Sutures in the TracheaFORGOTTEN FOREIGN BODIES IN BRONCHIAL TREE IN ADULT (A REPORT OF TWO CASES AND REVIEW OF LITERATURE)La fibrobroncoscopia en la extracción de cuerpos extraños traqueobronquiales en adultosBronchoscopic Procedures in the Intensive Care UnitThe Bronchoscopy Survey 15 September 1990Volume 113, Issue 6Page: 482-483KeywordsBronchoscopy ePublished: 1 December 2008 Issue Published: 15 September 1990 PDF downloadLoading ...
Late Prognosis of Chlorpromazine Jaundice
Authors: A. G. Melrose, J. R. Roy
Journal: BMJ (1959)

Jaundice, the best known of the complications of chlorpromazine therapy, has an incidence of about 1%The prevalence in a general hospital popuation has been investigated by Graham (1957), who noted that, of 55 patients admitted in one year suffering from jaundice, chlorpromazine was the cause in five cases.The clinical, pathological, and biochemical features have been extensively investigated-for example, by Werther and Korelitz (1957)-and are now well recognized.It is believed that jaundice is caused by hypersensitivity to the drug within the liver, which may result in an iicreased permeability of the cholangioles (British Medical Journal, 1957).The characteristic histological picture is one of biiary stasis, with infiltration of the portal tracts by polymorphs, among which eosinophils are frequent; Portal-zone fibrosis and hepatic cellular
Pulmonary Scintiangiography in the Diagnosis of Thromboembolism
Authors: GEORGE W. EVANS, JAMES H. KIERAN, SHEILA M. WILLIAMSON, HUGH F. McCARTHY, F GREGORY CURTIN, FRANCIS H. HINNENDAEL
Journal: Clinical Nuclear Medicine (1977)

The scintiangiographic technique can be a significant aid in the differential diagnosis of pulmonary thromboembolic disease. It adds nothing in the way of time or difficulty to the study, the cost is trivial, and taken together with standard perfusion and ventilation studies, the scintiangiographic technique increases the diagnostic usefulness of the lung scan for pulmonary thromboembolic disease. It adds to the other modalities information which may prove relevant to modification of therapy and to prognosis and can yield significant information about the heart, pericardium, and great vessels related or unrelated to the diagnosis of PTE.
Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct.
Authors: R A Star, H Nonoguchi, R Balaban, M A Knepper
Journal: Journal of Clinical Investigation (1988)

Vasopressin increases both the urea permeability and osmotic water permeability in the terminal part of the renal inner medullary collecting duct (terminal IMCD). To identify the second messengers that mediate these responses, we measured urea permeability, osmotic water permeability, intracellular calcium concentration, and cyclic AMP accumulation in isolated terminal IMCDs. After addition of vasopressin, a transient rise in intracellular calcium occurred that was coincident with increases in cyclic AMP accumulation and urea permeability. Half-maximal increases in urea permeability and osmotic water permeability occurred with 0.01 nM vasopressin. The threshold concentration for a measurable increase in cyclic AMP accumulation was approximately 0.01 nM, while measurable increases in intracellular calcium required much higher vasopressin concentrations (greater than 0.1 nM). Exogenous cyclic AMP (1 mM 8-Br-cAMP) mimicked the effect of vasopressin on urea permeability but did not produce a measurable change in intracellular calcium concentration. Conclusions: (a) Cyclic AMP is the second messenger that mediates the urea permeability response to vasopressin in the rat terminal IMCD. (b) Vasopressin increases the intracellular calcium concentration in the rat terminal IMCD, but the physiological role of this response is not yet known.
A Liver-Derived Secretory Protein, Selenoprotein P, Causes Insulin Resistance
Authors: Hirofumi Misu, Toshinari Takamura, Hiroaki Takayama, Hiroto Hayashi, Naoto Matsuzawa-Nagata, Seiichiro Kurita, Kazuhide Ishikura, Hitoshi Ando, Yumie Takeshita, Tsuguhito Ota, Masaru Sakurai, Tatsuya Yamashita, Eishiro Mizukoshi, Taro Yamashita, Masao Honda, Ken-ichi Miyamoto, Tetsuya Kubota, Naoto Kubota, Takashi Kadowaki, Han-Jong Kim, In-kyu Lee, Yasuhiko Minokoshi, Yoshiro Saito, Kazuhiko Takahashi, Yoshihiro Yamada, Nobuyuki Takakura, Shuichi Kaneko
Journal: Cell Metabolism (2010)
TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice
Authors: Line S. Reinert, Louis Harder, Christian K. Holm, Marie B. Iversen, Kristy A. Horan, Frederik Dagnæs-Hansen, Benedicte P. Ulhøi, Thomas H. Holm, Trine H. Mogensen, Trevor Owens, Jens R. Nyengaard, Allan R. Thomsen, Søren R. Paludan
Journal: Journal of Clinical Investigation (2012)

Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation events. Immunological control of HSV involves activation of innate immune pattern-recognition receptors such as TLR3, which detects double-stranded RNA and induces type I IFN expression. Humans with defects in the TLR3/IFN pathway have an elevated susceptibility to HSV infections of the CNS. However, it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune responses to HSV, but astrocytes were defective in HSV-induced type I IFN production. Thus, TLR3 acts in astrocytes to sense HSV-2 infection immediately after entry into the CNS, possibly preventing HSV from spreading beyond the neurons mediating entry into the CNS.
Persistent Postoperative Incisional Pain
Authors: Franklin J. Day
Journal: JAMA (1988)

<h3>To the Editor.</h3> —In the Feb 19, 1988, issue ofThe Journalthere was a question regarding persistent postoperative incisional pain following cholecystectomy. The answer by Dr Hermann<sup>1</sup>suggested nonspecific measures for treatment of this kind of problem, but failed to mention the most common reason for undiagnosed persistent postoperative pain: development of a deafferentation-type pain, most commonly called<i>reflex sympathetic dystrophy</i>. While classically described as occurring in extremities, this type of pain can occur in any area of the body. Deafferentation-type pain occurs about 2% to 5% of the time after injury to afferent nerves and frequently is resistant to all forms of conventional therapy. Its etiology is not known. The pain can last months or years, and while many "conservative" therapies have been proposed to treat this disorder, the only reliably effective treatment is interruption of the sympathetic nerves to the area concerned. While injection of the
Adenosine deaminase deficiency with mosaicism for a “second-site suppressor” of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy
Authors: Francisco X. Arredondo-Vega, Ines Santisteban, Eva Richard, Pawan Bali, Majed Koleilat, Michael Loubser, Abdulaziz Al-Ghonaium, Mariam Al-Helali, Michael S. Hershfield
Journal: Blood (2002)
The Intern and Sleep Loss
Authors: Richard C. Friedman, J. Thomas Bigger, Donald S. Kornfeld
Journal: New England Journal of Medicine (1971)

Abstract To investigate the effects of sleep deprivation on medical interns, an electrocardiographic arrhythmia-detection task and questionnaires assessing mood and subjectively perceived psychophysiologic state were administered. In comparison to their performance when rested, interns deprived of sleep were significantly less able to recognize arrhythmias on the electrocardiographic task. Mood was significantly affected by sleep loss; deprived interns felt increased sadness and decreased vigor, egotism and social affection. In addition, numerous psychopathologic symptoms developed, and they judged themselves to have abnormalities in cognitive, perceptual and physiologic areas of function. It is apparent that interns deprived of normal sleep may experience transient psychopathology and impaired efficiency of performance.