tbuckley/cabot-search huggingface dataset:
The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome
Authors: Christian Buske, Eva Hoster, Martin Dreyling, Joerg Hasford, Michael Unterhalt, Wolfgang Hiddemann
Journal: Blood (2006)
Suppression of FVIII Inhibitor Formation in Hemophilic Mice by Delivery of Transgene Modified Apoptotic Fibroblasts
Authors: Rui-Jun Su, Angela Epp, Yvette Latchman, Doug Bolgiano, Steven W Pipe, Neil C Josephson
Journal: Molecular Therapy (2009)

The development of inhibitory antibodies to factor VIII (FVIII) is currently the most significant complication of FVIII replacement therapy in the management of patients with severe hemophilia A. Immune tolerance protocols for the eradication of inhibitors require daily delivery of intravenous FVIII for at least 6 months and are unsuccessful in 20–40% of treated patients. We hypothesize that tolerance can be induced more efficiently and reliably by delivery of FVIII antigen within autologous apoptotic cells (ACs). In this study, we demonstrated suppression of the T cell and inhibitor responses to FVIII by infusion of FVIII expression vector modified apoptotic syngeneic fibroblasts in both naive and preimmunized hemophilia A mice. ACs without FVIII antigen exerted modest generalized immune suppression mediated by anti-inflammatory signals. However, FVIII expressing apoptotic syngeneic fibroblasts produced much stronger antigen-specific immune suppression. Mice treated with these fibroblasts generated CD4+ T cells that suppressed the immune response to FVIII after adoptive transfer into naive recipients and antigen-specific CD4+CD25+ regulatory T cells (Tregs) that inhibited the proliferation of FVIII responsive effector T cells in vitro. These preclinical results demonstrate the potential for using FVIII vector modified autologous ACs to treat high-titer inhibitors in patients with hemophilia A. The development of inhibitory antibodies to factor VIII (FVIII) is currently the most significant complication of FVIII replacement therapy in the management of patients with severe hemophilia A. Immune tolerance protocols for the eradication of inhibitors require daily delivery of intravenous FVIII for at least 6 months and are unsuccessful in 20–40% of treated patients. We hypothesize that tolerance can be induced more efficiently and reliably by delivery of FVIII antigen within autologous apoptotic cells (ACs). In this study, we demonstrated suppression of the T cell and inhibitor responses to FVIII by infusion of FVIII expression vector modified apoptotic syngeneic fibroblasts in both naive and preimmunized hemophilia A mice. ACs without FVIII antigen exerted modest generalized immune suppression mediated by anti-inflammatory signals. However, FVIII expressing apoptotic syngeneic fibroblasts produced much stronger antigen-specific immune suppression. Mice treated with these fibroblasts generated CD4+ T cells that suppressed the immune response to FVIII after adoptive transfer into naive recipients and antigen-specific CD4+CD25+ regulatory T cells (Tregs) that inhibited the proliferation of FVIII responsive effector T cells in vitro. These preclinical results demonstrate the potential for using FVIII vector modified autologous ACs to treat high-titer inhibitors in patients with hemophilia A.
Immunoneutralization of Glycoprotein Ibα Attenuates Endotoxin-Induced Interactions of Platelets and Leukocytes With Rat Venular Endothelium In Vivo
Authors: Tomihiro Katayama, Yasuo Ikeda, Makoto Handa, Takuya Tamatani, Shinji Sakamoto, Masaharu Ito, Yuzuru Ishimura, Makoto Suematsu
Journal: Circulation Research (2000)

Abstract —This study aimed to examine molecular mechanisms for endotoxin-induced adhesive changes in platelets in vivo. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester were visualized in rat mesenteric venules through intravital microscopy assisted by a high-speed fluorescence video imager at 1000 frames per second or by a normal-speed intensifier under monitoring of erythrocyte velocity. Leukocyte rolling was examined by normal-speed transmission video images. The velocity of platelets traveling along the centerline of venules followed that of erythrocytes, whereas that measured at the periendothelial space was significantly smaller than the erythrocyte velocity; a majority of these cells exhibited transient but notable rolling with endothelium. Administration of endotoxin increased the density of periendothelial platelets and reduced the rolling velocities of platelets and leukocytes in venules: All events were attenuated by anti–rat P-selectin monoclonal antibody s789G or by anti–human glycoprotein (GP) Ibα monoclonal antibody GUR83/35, which blocks ristocetin-induced aggregation of rat platelets. Isolated rat platelets injected into endotoxin-pretreated rats were able to roll on the venules. This event was attenuated by pretreatment of platelets in vitro with GUR83/35 but not with s789G, suggesting involvement of endothelial P-selectin and platelet GP Ibα in the endotoxin-induced responses. Furthermore, isolated human platelets showed similar rolling interactions with endotoxin-preexposed rat venules, and pretreatment of the platelets with GUR83/35, but not with s789G, significantly reduced such interactions. Our results provide the first evidence for involvement of GP Ibα in endotoxin-induced microvascular rolling of platelets and leukocytes, and this system serves as a potentially useful tool to examine GP Ibα–associated function of human platelets in vivo.
Computers and Clinical Work
Authors: M. I. Harrison
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hormonal control of substrate cycling in humans.
Authors: H Miyoshi, G I Shulman, E J Peters, M H Wolfe, D Elahi, R R Wolfe
Journal: Journal of Clinical Investigation (1988)

Recent studies have established the existence of substrate cycles in humans, but factors regulating the rate of cycling have not been identified. We have therefore investigated the acute response of glucose/glucose-6P-glucose (glucose) and triglyceride/fatty acid (TG/FA) substrate cycling to the infusion of epinephrine (0.03 microgram/kg.min) and glucagon. The response to a high dose glucagon infusion (2 micrograms/kg.min) was tested, as well as the response to a low dose infusion (5 ng/kg.min), with and without the simultaneous infusion of somatostatin (0.1 microgram/kg.min) and insulin (0.1 mU/kg.min). Additionally, the response to chronic prednisone (50 mg/d) was evaluated, both alone and during glucagon (low dose) and epinephrine infusion. Finally, the response to hyperglycemia, with insulin and glucagon held constant by somatostatin infusion and constant replacement of glucagon and insulin at basal rates, was investigated. Glucose cycling was calculated as the difference between the rate of appearance (Ra) of glucose as determined using 2-d1- and 6,6-d2-glucose as tracers. TG/FA cycling was calculated by first determining the Ra glycerol with d5-glycerol and the Ra FFA with [1-13C]palmitate, then subtracting Ra FFA from three times Ra glycerol. The results indicate that glucagon stimulates glucose cycling, and this stimulatory effect is augmented when the insulin response to glucagon infusion is blocked. Glucagon had minimal effect on TG/FA cycling. In contrast, epinephrine stimulated TG/FA cycling, but affected glucose cycling minimally. Prednisone had no direct effect on either glucose or TG/FA cycling, but blunted the stimulatory effect of glucagon on glucose cycling. Hyperglycemia, per se, had no direct effect on glucose or TG/FA cycling. Calculations revealed that stimulation of TG/FA cycling theoretically amplified the sensitivity of control of fatty acid flux, but no such amplification was evident as a result of the stimulation of glucose cycling by glucagon.
Hypoxia-Dependent Regulation of Nonphagocytic NADPH Oxidase Subunit NOX4 in the Pulmonary Vasculature
Authors: Manish Mittal, Markus Roth, Peter König, Simone Hofmann, Eva Dony, Parag Goyal, Anne-Christin Selbitz, Ralph Theo Schermuly, Hossein Ardeschir Ghofrani, Grazyna Kwapiszewska, Wolfgang Kummer, Walter Klepetko, Mir Ali Reza Hoda, Ludger Fink, Jörg Hänze, Werner Seeger, Friedrich Grimminger, Harald H.H.W. Schmidt, Norbert Weissmann
Journal: Circulation Research (2007)

Nonphagocytic NADPH oxidases have recently been suggested to play a major role in the regulation of physiological and pathophysiological processes, in particular, hypertrophy, remodeling, and angiogenesis in the systemic circulation. Moreover, NADPH oxidases have been suggested to serve as oxygen sensors in the lung. Chronic hypoxia induces vascular remodeling with medial hypertrophy leading to the development of pulmonary hypertension. We screened lung tissue for the expression of NADPH oxidase subunits. NOX1, NOXA1, NOXO1, p22phox, p47phox, p40phox, p67phox, NOX2, and NOX4 were present in mouse lung tissue. Comparing mice maintained for 21 days under hypoxic (10% O 2 ) or normoxic (21% O 2 ) conditions, an upregulation exclusively of NOX4 mRNA was observed under hypoxia in homogenized lung tissue, concomitant with increased levels in microdissected pulmonary arterial vessels. In situ hybridization and immunohistological staining for NOX4 in mouse lungs revealed a localization of NOX4 mRNA and protein predominantly in the media of small pulmonary arteries, with increased labeling intensities after chronic exposure to hypoxia. In isolated pulmonary arterial smooth muscle cells (PASMCs), NOX4 was localized primarily to the perinuclear space and its expression levels were increased after exposure to hypoxia. Treatment of PASMCs with siRNA directed against NOX4 decreased NOX4 mRNA levels and reduced PASMC proliferation as well as generation of reactive oxygen species. In lungs from patients with idiopathic pulmonary arterial hypertension (IPAH), expression levels of NOX4, which was localized in the vessel media, were 2.5-fold upregulated. These results support an important role for NOX4 in the vascular remodeling associated with development of pulmonary hypertension.
Adult Cancer Clinical Trials That Fail to Complete: An Epidemic?
Authors: Kristian D. Stensland, Russell B. McBride, Asma Latif, Juan Wisnivesky, Ryan Hendricks, Nitin Roper, Paolo Boffetta, Simon J. Hall, William K. Oh, Matthew D. Galsky
Journal: JNCI Journal of the National Cancer Institute (2014)

The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent rate-limiting factors in the effort to translate preclinical discoveries into the next generation of standard therapeutic approaches. Optimal use of resources requires understanding and ultimately addressing inefficiencies in the cancer clinical trials system. Prior analyses have demonstrated that a large proportion of trials initiated by the National Cancer Institute (NCI) Cooperative Group system are never completed. While NCI Cooperative Group trials are important, they represent only a small proportion of all cancer clinical trials performed. Herein, we explore the problem of cancer clinical trials that fail to complete within the broader cancer clinical trials enterprise. Among 7776 phase II-III adult cancer clinical trials initiated between 2005-2011, we found a seven-year cumulative incidence of failure to complete of approximately 20% (95% confidence interval = 18% to 22%). Nearly 48000 patients were enrolled in trials that failed to complete. These trials likely contribute little to the scientific knowledge base, divert resources and patients from answering other critical questions, and represent a barrier to progress.
A neutral lipid envelope-type nanoparticle composed of a pH-activated and vitamin E-scaffold lipid-like material as a platform for a gene carrier targeting renal cell carcinoma
Authors: Hidetaka Akita, Ryohei Ishiba, Ryohei Togashi, Kota Tange, Yuta Nakai, Hiroto Hatakeyama, Hideyoshi Harashima
Journal: Journal of Controlled Release (2014)
CDC and FDA Response to Risk of Confusion in Dosing Tamiflu Oral Suspension
Authors: Daniel S. Budnitz, Linda L. Lewis, Nadine Shehab, Debra Birnkrant
Journal: New England Journal of Medicine (2009)

To the Editor: On September 23, Parker et al.1 described a case in which Tamiflu (oseltamivir) for oral suspension was dispensed with pharmacy instructions to administer the drug in volume units (t...
What Constitutes Readable Print? Satinized, Light-Reflecting White Paper Fatigues the Eye.
Authors: William B. Meany
Journal: JAMA (1897)

St. Louis, Mo., May 15, 1897. <h3>To the Editor:</h3> — I herewith send you a few crumbs in answer to your call for a discussion of the paper on which theJournalshould be printed, because I am convinced that it will be calculated to do good service by directing attention to very important questions, which must be of great practical interest to the human race both in this and future generations. The question of the size and form of printing type, and the color of the material for background, is not only of great importance to the comfort of adults, but it is of far greater importance to children and those who quite naturally look to the typographical and mechanical features of theJournalfor a model. What constitutes readable print? The most readable print is that by which one may obtain the maximum of reading, with the minimum
Poor Survival Associated with the <i>BRAF</i> V600E Mutation in Microsatellite-Stable Colon Cancers
Authors: Wade S. Samowitz, Carol Sweeney, Jennifer Herrick, Hans Albertsen, Theodore R. Levin, Maureen A. Murtaugh, Roger K. Wolff, Martha L. Slattery
Journal: Cancer Research (2005)

Abstract The BRAF V600E mutation has been associated with microsatellite instability and the CpG island methylator phenotype (CIMP) in colon cancer. We evaluated a large population-based sample of individuals with colon cancer to determine its relationship to survival and other clinicopathologic variables. The V600E BRAF mutation was seen in 5% (40 of 803) of microsatellite-stable tumors and 51.8% (43 of 83) of microsatellite-unstable tumors. In microsatellite-stable tumors, this mutation was related to poor survival, CIMP high, advanced American Joint Committee on Cancer (AJCC) stage, and family history of colorectal cancer [odds ratio, 4.23; 95% confidence interval (95% CI), 1.65-10.84]. The poor survival was observed in a univariate analysis of 5-year survival (16.7% versus 60.0%; P &amp;lt; 0.01); in an analysis adjusted for age, stage, and tumor site [hazard rate ratio (HRR), 2.97; 95% CI, 2.05-4.32]; in stage-specific, age-adjusted analyses for AJCC stages 2 to 4 (HRR, 4.88, 3.60, and 2.04, respectively); and in Kaplan-Meier survival estimates for AJCC stages 2 to 4 (P &amp;lt; 0.01 for all three stages). Microsatellite-unstable tumors were associated with an excellent 5-year survival whether the V600E mutation was present or absent (76.2% and 75.0%, respectively). We conclude that the BRAF V600E mutation in microsatellite-stable colon cancer is associated with a significantly poorer survival in stages 2 to 4 colon cancer but has no effect on the excellent prognosis of microsatellite-unstable tumors.
Costal Cartilage Calcification Presenting a Doughnut Appearance on 99mTc-Pyrophosphate Myocardial Imaging
Authors: F L DATZ, W R GRAY, S E LEWIS, J T WILLERSON, R W PARKEY
Journal: Clinical Nuclear Medicine (1979)

DATZ, F L M.D.; GRAY, W R M.D.; LEWIS, S E M.D., M.S.E.E.; WILLERSON, J T M.D.; PARKEY, R W M.D. Author Information
What Three Wise Men have to say about diagnosis
Authors: N. Mani, N. Slevin, A. Hudson
Journal: BMJ (2011)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following What Three Wise Men have to say about diagnosis Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
US Catholic bishops mount two week national anticontraception campaign
Authors: J. H. Tanne
Journal: BMJ (2012)

The US Conference of Catholic Bishops has launched a “fortnight for freedom” campaign to demonstrate its opposition to the federal government’s requirement that health insurance policies include coverage for contraception from 1 August.

The bishops’ campaign begins on 21 June and ends on 4 July, when the US celebrates its biggest national holiday, Independence Day. There will be a nationally televised mass at the Basilica of the National Shrine of the Immaculate Conception in Washington, DC.

The bishops sent out a nationwide bulletin, an insert that parishes can use in their newsletters. It quotes Martin Luther King, who wrote, “I would agree with St Augustine that ‘an unjust law is no law at all’ . . . A just law is a man made code that squares with the moral law or the law of God. An unjust law is a code that is out …
A video terminal--light-pen device for ordering medical tests
Authors: R. G. Siekert
Journal: JAMA (1968)

In order for a physician to obtain the advantage of an automated laboratory ordering and reporting system, he must have easy access to the system. The access device or technique should be easy to use and should require no new skills. A television screen with a light-pen pointer was found acceptable. Furthermore, the laboratory tests may be organized in several ways, enabling the user to order appropriate clusters of tests.
Contact Lens Care in the Third World
Authors: Donald L. Blanchard
Journal: JAMA (1987)

To the Editor.—  Recently, I read about contact lens care in underdeveloped countries in the QUESTIONS AND ANSWERS section of JAMA . 1 I feel that the answer was unduly pessimistic. The statement that  solutions do not provide any sterilizing activity is inaccurate.  The various commercially available cold sterilization regimens do provide disinfecting activity, although they do not achieve absolute sterility of the contact lens overnight.  As an example, Opti Soft solution, among other disinfecting activities, eliminates 90% of a microbial population of Pseudomonas aeruginosa , the cause of serious corneal ulcers, in four hours' soaking.  As indicated in the answer, cleanliness and consistency are extremely important. With the available self-contained cleaning and soaking sterilizing sets, tap water is not necessary, no matter how it is pretreated. This means that a person with contact lenses can travel to remote areas without being at the mercy of local hygiene conditions.
Apolipoprotein E-ϵ4 protects against severe liver disease caused by hepatitis C virus
Authors: Matthew A. Wozniak, Ruth F. Itzhaki, Brian E. Faragher, Martin W. James, Steven D. Ryder, William L. Irving
Journal: Hepatology (2002)

The outcome of infection with hepatitis C virus (HCV) varies greatly. The virus associates with serum lipoproteins, including those containing apolipoprotein E (apoE) and apolipoprotein B (apoB), and may enter cells via the low-density lipoprotein receptor (LDLR). ApoE genotypes can affect the extent of damage in diseases caused by 2 other viruses--herpes simplex virus type 1 (HSV1; in Alzheimer's disease and herpes labialis) and human immunodeficiency virus (HIV). We therefore investigated whether specific apoE and apoB alleles were associated with different outcomes of HCV infection. A total of 156 anti-HCV-positive patients and 104 non-HCV-infected patients were studied. Liver biopsy specimens from patients with chronic HCV infection (n = 111) were assessed for disease severity by the Knodell system. ApoE and apoB genotypes were determined by standard polymerase chain reaction (PCR) methods. There was no significant difference among the apoE genotypes of HCV-infected subjects compared with previously published population data, or between HCV-RNA positive or negative patients. However, chronically HCV-infected subjects with mild liver disease (n = 65) had a significantly higher apoE-epsilon 4 allele frequency (20.0%) than those (n = 46) with severe disease (6.5%). ApoB alleles alone or in combination with apoE were not associated with mild or severe disease. The overall apoE allele frequencies of patients with liver disease not caused by HCV were similar to those of the total HCV group and in contrast to the HCV patients, the apoE allele frequencies were similar in those patients with no or mild fibrosis as compared with those with bridging fibrosis or cirrhosis. In conclusion, carriage of an apoE-epsilon 4 allele may be protective against liver damage caused by HCV, but not against damage due to various nonviral causes. This is yet another case in which apoE may determine the severity of a viral disease.
How PR firms use research to sell products
Authors: Petra Boynton, Sara Shaw, Will Callaghan
Journal: BMJ (2004)

In the past month we have seen some pretty astonishing research. Studies have proved that moving to the countryside, drinking wine, or discussing your relationship problems in bed can improve sexual problems. Owning a pet helps you recover more quickly from illness, testosterone causes unsafe sex, and if your eyes are brown or green they are officially the “wrong” colour. But texting is good for your mental health.

You may not have been privy to these discoveries unless, like us, you have an interest in what research appears in the lay media, or are regularly targeted by public relations companies.

While many questions have been asked about research undertaken by pharmaceutical companies, until …
Drug companies succeed in keeping payments to doctors secret
Authors: B. Burton
Journal: BMJ (2003)

Lobbying by Australia's drug industry association, Medicines Australia, has persuaded the Australian Competition and Consumer Commission (ACCC) to scrap a proposal to require public disclosure of drug companies' sponsorship of doctors' travel and accommodation and other promotional benefits.

The commission, a government agency established to protect consumers from anticompetitive activity, had originally proposed accrediting a self regulatory code on the marketing of drugs developed by Medicines Australia member companies, subject to certain amendments.

The first amendment laid down that Medicines Australia publish details of all breaches of the code on its website in full and …