tbuckley/cabot-search huggingface dataset:
Signal transduction by tumour necrosis factor and tumour necrosis factor related ligands and their receptors
Authors: B. G Darnay, B. B Aggarwal
Journal: Annals of the Rheumatic Diseases (1999)

Many biological functions are regulated through interactions of extracellular molecules with their cognate cell surface receptors. The transduction of these signals by their receptors at the plasma membrane to the intracellular machinery results in such cellular activities as gene activation, protein phosphorylation, cell proliferation, and cell destruction. Though the kinetics of these activities may differ, their interactions are coordinated by selective interplay between the receptors' intracellular domains and a select set of intracellular receptor binding proteins. One such family of extracellular molecules and their cell-surface receptors are the tumour necrosis factor (TNF) family of related cytokines and receptors, which is the topic of this review.

Rheumatoid arthritis, a disease of joint inflammation and destruction, is the result of inappropriate activation of resident and inflammatory cells within the synovial tissue. The consequence of an initiating and as yet unknown stimulus, the cascade of inflammatory processes are chronic and self perpetuating. The inflammation in the joints characteristic of arthritis is believed to be atrributable largely to misregulation of cytokine production, abnormal expression of receptors, or the absence of counter-regulatory pathways. Two proinflammatory cytokines, TNF and interleukin 1 (IL1), are believed to be the major cytokines cooperating in the pathology of this disease.1Therapeutic approaches that inhibit the interaction of these ligands with their receptors has been a successful avenue in the treatment of rheumatoid arthritis.2 

One characteristic common to both TNF and IL1 is their ability to activate the transcription factor nuclear factor-kappa B (NF-κB), which is responsible for regulation of a number of genes necessary for the inflammation process.3 More recently, the elucidation of the TNF and IL1 signalling pathways has provided novel candidate molecules from which to develop therapeutic inhibitors that would block NF-κB activation. Furthermore, additional members of the TNF family have been discovered and are …
Undiagnosed Myocardial Infarction
Authors: Jonas Brachfeld
Journal: JAMA (1984)

<h3>To the Editor.—</h3> The recent correspondence inThe Journal<sup>1</sup>regarding failure to diagnose acute myocardial infarction prompts me to make the following comment. I have had the opportunity to collect data on a number of cases of missed myocardial infarction that had a fatal outcome and eventually came to litigation. Since my previous reporting of this experience,<sup>2,3</sup>I have reviewed several dozen more such cases. The process of selection of this series is entirely different, of course, but since the ultimate criteria are highly restrictive (fatality and litigation), these cases probably reflect the tip of the iceberg. One factor recurs monotonously in many cases. The diagnosis was missed because of excessive reliance on specific history (such as the nature or the radiation of the pain), physical examination, or laboratory findings. Not enough weight was given to the circumstances under which the patient came to medical attention. For example,
Delta Hearing Handicap and Presbycusis Software (V13)
Authors: Gerald R. Popelka
Journal: JAMA (1991)

This software package for the Macintosh computer is a stand-alone program that performs the computations for determination of percent hearing handicap. It accepts audiometric thresholds at six frequencies and computes percent handicap according to one of six methods (American Medical Association-1979; AMA-1959; National Institute for Occupational Safety and Health-Federal Employees Compensation Act, the state of Wisconsin, the state of Oregon, and the British Society of Audiology). Although the basic concept of the program is correct, and such a program can be useful, the implementation of this particular program has too many problems to warrant its recommendation. An interesting and useful function is the incorporation of corrections for presbycusis. The program accepts keyboard input of the patient's age, sex, and audiometric thresholds. It considers presbycusis effects to be additive with noiseinduced hearing loss (a widely accepted concept) and computes the percent handicap after subtracting the effects of presbycusis. This is a
Molecular insights gained from covalently tethering cGMP to the ligand-binding sites of retinal rod cGMP-gated channels
Authors: R. Lane Brown, Jeffrey W. Karpen
Journal: Behavioral and Brain Sciences (1995)

Abstract A photoaffinity analog of cGMP has been used to biochemically identify a new ligand-binding subunit of the retinal rod cGMP-activated ion channel, as well as amino acids in contact with cGMP in the original subunit. Covalent tethering of this probe to channels in excised menbrane patches has revealed a functional heteogeneity in the ligand-binding sites that may arise from the two biochemically identified subunits.
Stopping Antibiotics in Neutropenic Patients
Authors: JOHN S. CHEESBROUGH
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 June 1988Stopping Antibiotics in Neutropenic PatientsJOHN S. CHEESBROUGH, ALAN MURRAYJOHN S. CHEESBROUGHSearch for more papers by this author, ALAN MURRAYSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-6-908_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We congratulate Dr. DiNubile on his thoughtful article (1). His comments on the basis for current dogma dictating the use of antibiotics in such patients, particularly the scanty data on which it is founded, are apt. However, he may be extrapolating from centers where staff with adequate experience to detect the subtle signs of emerging infections are readily available to centers that may not be so fortunate. In such units, discontinuing antibiotics may be more hazardous and a rigid policy for introducing amphotericin B more appropriate. This potentially confounding variable is difficult to quantify and assess in...References1. DINUBILE M. Stopping antibiotic therapy in neutropoenic patients. Ann Intern Med. 1988;108:289-92. LinkGoogle Scholar2. ROSEJOHNSONMEAKINMACKIESTUART PSMPJ. Serial study of C-reactive protein during infection in leukaemia. J Clin Pathol. 1981;34:263-6. CrossrefMedlineGoogle Scholar3. PEPYS M. The Acute phase response and C reactive protein. In: Oxford Textbook of Medicine. 2nd ed. Oxford: Oxford Univ. Press, Inc.; 1987:9, 157-64. Google Scholar4. ROWEWORSLEYDONNELLY IAP. Measurement of serum C reactive protein concentration after bone marrow transplantation for leukaemia. J Clin Pathol. 1984;37:263-4. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JOHN S. CHEESBROUGH; ALAN MURRAYAffiliations: Royal Liverpool Hospital Liverpool L7 8XP England PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1988Volume 108, Issue 6Page: 908-908KeywordsAmphotericinAntibiotics ePublished: 1 December 2008 Issue Published: 1 June 1988 PDF downloadLoading ...
In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease
Authors: Raja Atreya, Helmut Neumann, Clemens Neufert, Maximilian J Waldner, Ulrike Billmeier, Yurdagül Zopf, Marcus Willma, Christine App, Tino Münster, Hermann Kessler, Stefanie Maas, Bernd Gebhardt, Ralph Heimke-Brinck, Eva Reuter, Frank Dörje, Tilman T Rau, Wolfgang Uter, Thomas D Wang, Ralf Kiesslich, Michael Vieth, Ewald Hannappel, Markus F Neurath
Journal: Nature Medicine (2014)
Plasticity of Foxp3+ T Cells Reflects Promiscuous Foxp3 Expression in Conventional T Cells but Not Reprogramming of Regulatory T Cells
Authors: Takahisa Miyao, Stefan Floess, Ruka Setoguchi, Hervé Luche, Hans Joerg Fehling, Herman Waldmann, Jochen Huehn, Shohei Hori
Journal: Immunity (2012)
Left ventricular relaxation and regional nonuniformity of early diastolic geometric changes in hypertrophic nonobstructive cardiomyopathy
Authors: Wataru Hayasaida, Toshiaki Kumada, Fujimasa Kohno, Michiyo Noda, Noboru Ishikawa, Chuichi Kawai
Journal: Journal of the American College of Cardiology (1991)
Filtration Fraction and its Implications for Radionuclide Renography Using Diethylenetriaminepentaacetic Acid and Mercaptoacetyltriglycine
Authors: Gary F. Gates
Journal: Clinical Nuclear Medicine (2004)

Purpose: Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 92 patients to calculate filtration fraction (GFR/EFPR) and evaluate its change in renal diseases. This information was used as the rationale for a renogram protocol using DTPA (to estimate GFR) and MAG3 (to produce images and curves). Methods: Individual kidney GFR and ERPF were determined by gamma camera techniques using Tc-99m DTPA and I-131 OIH. Two hundred sixty-one determinations were performed in 92 patients who in turn were grouped into 4 categories: normal, obstruction, renal vascular disease, and chronic insufficiency. Results: Mean filtration fractions in normal patients and those with obstruction were similar (0.16 and 0.15, respectively), whereas they were lower in renal vascular disease (0.11) and chronic renal insufficiency (0.08). Low filtration fraction indicates disproportionate loss of GFR compared with ERPF and was the pattern observed with advancing renal disease in most patients. The exception was ATN or contrast nephropathy when filtration fraction was increased (0.22) as a result of disproportionate loss of ERPF compared with GFR. Conclusions: OIH is no longer available in the United States, and MAG3 is now used as the renal tubular agent in renography. Clearance of MAG3 does not directly measure ERPF, but this might not be a significant loss in clinical practice if GFR is measured during renography because it is more adversely affected by renal disease than ERPF (with the exception of ATN and contrast nephropathy). Accordingly, a renogram protocol is presented for the combined use of DTPA and MAG3 resulting in GFR estimation (from DTPA) while yielding superior renal images and renogram curves from MAG3.
Doctors and the Dispensing of Drugs
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1987)

The U.S. House of Representatives is considering legislation that would restrict the conditions under which physicians could dispense prescription drugs to their patients. It is intended to curb a growing national practice in which physicians dispense drugs that they buy in individual prescription doses from repackaging drug wholesalers and then sell to their patients at a marked-up price. An estimated 5 percent of practitioners are now dispensing drugs in this manner, but the wholesalers are marketing aggressively, and some observers predict that as many as a third of all office-based physicians may be involved within a few years.The bill . . .
YC-1 prevents sodium nitroprusside-mediated apoptosis in vascular smooth muscle cells
Authors: S Pan
Journal: Cardiovascular Research (2003)

Objective: Nitric oxide signaling pathways are of central importance in both the maintenance of vascular homeostasis and the progression of vascular disease. Since smooth muscle cell apoptosis is associated with numerous vascular disorders, the authors investigated whether YC-1, a soluble guanylyl cyclase (sGC) activator, regulates apoptosis in vascular smooth muscle cells (VSMC). Methods and results: Sodium nitroprusside (SNP) (1 mM) induced cGMP (guanosine 3′:5′-cyclic monophosphate)-independent apoptosis in rat vascular smooth muscle cells using MTT assay and TUNEL-reaction techniques. Furthermore, sodium nitroprusside induced apoptosis via Bcl-2 down-regulation, cytochrome c release reaction, and caspase-3 activation by Western blotting analysis and enzymatic assay methods. YC-1 abolished these apoptotic signaling cascades and prevented apoptosis through a cGMP-involved pathway, and phosphatidylinositol (PI) 3-kinase behaved a downstream event in this pathway. Conclusions: These results suggest that YC-1 inhibits sodium nitroprusside-induced vascular smooth muscle cells apoptosis via a cGMP- and phosphatidylinositol 3-kinase-involved inhibition on Bcl-2 down-regulation/cytochrome c release/caspase-3 activation cascades. The ability of YC-1 to prevent smooth muscle cell apoptosis may play an important role in blocking lesion formation at sites of vascular injury.
5-Hydroxytryptamine in Hemorrhagic Shock.
Authors: Roy L. Swank
Journal: Annals of Internal Medicine (1964)

s1 October 19645-Hydroxytryptamine in Hemorrhagic Shock.Roy L. Swank, M.D., Ph.D., J. H. Fellman, Ph.D., Wolfgang Hissen, M.D.Roy L. Swank, M.D., Ph.D., J. H. Fellman, Ph.D., Wolfgang Hissen, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-805_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe addition of 5-hydroxytryptamine (serotonin) to blood, in vitro or in vivo, causes blood cells to aggregate. This observation stimulated a study of 5-hydroxytryptamine levels in the blood during hemorrhagic shock, a state in which aggregation of blood cells may become marked. 5-Hydroxytryptamine determined spectrofluorometrically increased slightly in portal venous and arterial whole blood and in portal venous plasma. However, when a radioactive technique was used large amounts of labeled material were found to be released into the portal venous blood. The platelets in blood of shocked animals were shown to be much more adhesive than platelets in control blood... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Portland, Ore PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1964Volume 61, Issue 4Page: 805-806KeywordsBloodBlood cellsBlood plasmaObservational studiesPlateletsSerotoninShock Issue Published: 1 October 1964 PDF downloadLoading ...
A Phase II Study of Induction Chemotherapy Followed by Thoracic Radiotherapy and Erlotinib in Poor-Risk Stage III Non–Small-Cell Lung Cancer: Results of CALGB 30605 (Alliance)/RTOG 0972 (NRG)
Authors: Rogerio Lilenbaum, Michael Samuels, Xiaofei Wang, Feng Ming Kong, Pasi A. Jänne, Gregory Masters, Sreedhar Katragadda, Lydia Hodgson, Jeffrey Bogart, Jeffrey Bradley, Everett Vokes
Journal: Journal of Thoracic Oncology (2014)
Effect of Caffeine Ingestion on Exhaled Nitric Oxide Measurements in Patients with Asthma
Authors: Elizabeth S. Taylor, Andrew D. Smith, Jan O. Cowan, G. Peter Herbison, D. Robin Taylor
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Exhaled nitric oxide (FENO) measurements may be influenced by a number of confounding factors. Reports have offered conflicting evidence as to whether caffeine consumption increases or decreases FENO. In this study we aimed to confirm whether caffeine ingestion affects FENO in patients with asthma. On two separate days, 20 patients with asthma (10 steroid-naive and 10 steroid-treated) received a standard cup of either caffeinated or noncaffeinated coffee (15 g) (control) in a randomized, double-blind, cross-over manner. FENO measurements were obtained at baseline, and 30, 60, 120, and 180 minutes after ingestion. Serum caffeine levels were also measured at 0 and 60 minutes. No significant changes in FENO occurred after caffeine compared with the control. We conclude that caffeinated foods and beverages are unlikely to acutely influence FENO in subjects with asthma, and protocols for laboratory measurement do not need to take this factor into account.
Microstructural Impact of Ischemia and Bone Marrow–Derived Cell Therapy Revealed With Diffusion Tensor Magnetic Resonance Imaging Tractography of the Heart In Vivo
Authors: David E. Sosnovik, Choukri Mekkaoui, Shuning Huang, Howard H. Chen, Guangping Dai, Christian T. Stoeck, Soeun Ngoy, Jian Guan, Ruopeng Wang, William J. Kostis, Marcel P. Jackowski, Van J. Wedeen, Sebastian Kozerke, Ronglih Liao
Journal: Circulation (2014)

The arrangement of myofibers in the heart is highly complex and must be replicated by injected cells to produce functional myocardium. A novel approach to characterize the microstructural response of the myocardium to ischemia and cell therapy, with the use of serial diffusion tensor magnetic resonance imaging tractography of the heart in vivo, is presented.
STUDIES ON SERUM PROTEOLYTIC ENZYME INHIBITION
Authors: Frederic C. Moll
Journal: The Journal of Experimental Medicine (1956)

Serial studies of the serum levels of trypsin inhibitor have been performed on monkeys following injection of turpentine-falba, total body irradiation, thermal injury, splenectomy, administration of cortisone acetate and egg albumin. Following the injection of turpentine-falba mixture there was a prompt elevation in the trypsin inhibitor power of the serum. A similar response accompanied the administration of cortisone acetate. The response to cortisone was not inhibited by removal of the spleen. Animals premedicated with cortisone acetate for 3 and 4 weeks showed no statistically significant change in the level of the serum inhibitor following injection of the turpentine-falba. Total body irradiation and immunization with egg albumin were accompanied by a very slight rise in the inhibitory power of the serum despite a prompt and extensive drop in the total white blood cell count in the irradiated animals, and development of precipitins in all of the immunized animals. The significance of these findings is discussed.
Cyclin D1 Is Necessary for Tamoxifen-Induced Cell Cycle Progression in Human Breast Cancer Cells
Authors: Robin L. Kilker, Maricarmen D. Planas-Silva
Journal: Cancer Research (2006)

Abstract Despite the success of tamoxifen in treating hormone-responsive breast cancer, its use is limited by the development of resistance to the drug. Understanding the pathways involved in the growth of tamoxifen-resistant cells may lead to new ways to treat tamoxifen-resistant breast cancer. Here, we investigate the role of cyclin D1, a mediator of estrogen-dependent proliferation, in growth of tamoxifen-resistant cells using a cell culture model of acquired resistance to tamoxifen. We show that tamoxifen and 4-hydroxytamoxifen (OHT) promoted cell cycle progression of tamoxifen-resistant cells after growth-arrest mediated by the estrogen receptor down-regulator ICI 182,780. Down-regulation of cyclin D1 with small interfering RNA blocked basal cell growth of tamoxifen-resistant cells and induction of cell proliferation by OHT. In addition, pharmacologic inhibition of phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 pathways decreased basal cyclin D1 expression and impaired OHT-mediated cyclin D1 induction and cell cycle progression. These findings indicate that cyclin D1 expression is necessary for proliferation of tamoxifen-resistant cells and for tamoxifen-induced cell cycle progression. These results suggest that therapeutic strategies to block cyclin D1 expression or function may inhibit development and growth of tamoxifen-resistant tumors. (Cancer Res 2006; 66(23): 11478-84)
Abstract 2494: A non-covalent binding platinum drug, TriplatinNC, induces a G1 phase cell cycle arrest and p53-independent mechanisms of apoptosis
Authors: Peyman Kabolizadeh, Ralph Kipping, Vijay Menon, John Ryan, Erica Peterson, Lawrence Povirk, Nicholas Farrell
Journal: Cancer Research (2010)

Abstract TriplatinNC, is a novel trinuclear derivative of the Phase II clinical drug, BBR3464. The binding to DNA is through non-covalent (hydrogen bonding and electrostatic) interactions. The absence of substation-labile leaving groups results in insensitivity to glutathione concentration in vitro while the high (8+) charge results in enhanced cellular accumulation compared to BBR3464 and especially cisplatin. The antitumor activity of TriplatinNC was examined in vivo showing higher activity against 2008 ovarian carcinoma cells than c-DDP at the doses administered. Studies using HCT116 colon carcinoma cells have shown that TriplatinNC is cytotoxic in the presence and absence of p53. Cell cycle studies show that TriplatinNC differs from BBR3464 in inducing a G1 arrest rather than a G2 arrest in HCT116 cells. A p53-independent activation of caspase 8 and caspase 9 leading to the cleavage of caspase 3 and its downstream substrate, PARP-1, may indicate that TriplatinNC induces both intrinsic and extrinsic pathways of cell death. Our study illustrates fundamental differences in the mechanisms of action between non-covalent binding drugs like TriplatinNC and related covalent binding drugs such as c-DDP, oxaliplatin, and BBR3464. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2494.
Epidemiological study of asymptomatic inflammatory bowel disease: the identification of cases during a screening programme for colorectal cancer.
Authors: J F Mayberry, K C Ballantyne, J D Hardcastle, C Mangham, G Pye
Journal: Gut (1989)

An asymptomatic population of 37,000 people in the Nottingham area were offered faecal occult blood tests in a screening study for colorectal cancer. Seventeen thousand nine hundred and thirty people completed the tests and 481 individuals with positive tests underwent full investigation of the colon. Eight people with previously undiagnosed inflammatory bowel disease were identified. In five cases there was total ulcerative colitis; in one a proctitis and in two Crohn's disease. Two further patients with ulcerative colitis were identified; they had been lost to follow up for 25 and 45 years respectively. The combined prevalence of inflammatory bowel disease was 56/10(5) and it is likely that current studies of the epidemiology of these conditions may underestimate the true prevalence by between 27% and 38%.
Rubella vaccination: remaining problems.
Authors: J E Banatvala
Journal: BMJ (1982)

Rubella vaccination: remaining problemsRubella vaccines were first licensed over 12 years ago both in the United States and in Britain.The two countries have different vaccination policies.In the United States the vaccine programme was at first directed toward prepubertal children of both sexes' with the aim of substituting vaccine-induced infection for naturally acquired disease, thereby reducing the risk of transmitting rubella to pregnant women.This strategy was also intended to reduce the need for hazardous vaccination during pregnancy or at an'age when reactions are more likely to occur.The programme has resulted2 in a noticeable decline in both congenitally acquired as well as postnatally acquired rubella, at first among those aged under 15.2During 1978 and 1979, however, susceptibility and attack rates rose among adolescents and young adults.Numerous outbreaks of rubella among students, soldiers, and hospital staff showed an immunity gap; this has since been closed with a resulting substantial reduction in rubella notifications among all age groups, but mostly in the 15-24-year-olds.In 1980 only 3904 cases of rubella were notified,' 6700 less than in the previous year; figures so far available for 1981 are even better.3Despite these encouraging findings some rather disquieting evidence was produced by Horstmann4 and Balfour and Amren,5 who showed that 29 out of 342 (8 50') and 58 out of 159 (360 ) children, respectively, lacked haemagglutination inhibition antibody when tested three to nine years after vaccination with the HPV77-DE5 vaccine.Subsequent