tbuckley/cabot-search huggingface dataset:
Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling
Authors: Eng-Juh Yeoh, Mary E Ross, Sheila A Shurtleff, W.Kent Williams, Divyen Patel, Rami Mahfouz, Fred G Behm, Susana C Raimondi, Mary V Relling, Anami Patel, Cheng Cheng, Dario Campana, Dawn Wilkins, Xiaodong Zhou, Jinyan Li, Huiqing Liu, Ching-Hon Pui, William E Evans, Clayton Naeve, Limsoon Wong, James R Downing
Journal: Cancer Cell (2002)
Effects of chronic PGHS-2 inhibition on PGHS-dependent vasoconstriction in the aged female rat
Authors: S Armstrong
Journal: Cardiovascular Research (2003)

Objective: In menopause, aging and decreased estrogen levels are risk factors contributing to impaired vascular function. Previously, in a young ovariectomized rat model, we demonstrated an increase in prostaglandin H synthase (PGHS)-dependent vasoconstriction that could be prevented by estrogen replacement. Subsequently, we found that, with aging, estrogen acts through suppression of the PGHS-2 isoform. Hypothesis: Chronic PGHS-2 inhibition reduces PGHS-dependent vasoconstriction in aging. Methods: Ovariectomized, aged (12 months) Sprague–Dawley rats were treated with a placebo (n = 7), or the PGHS-2 inhibitor (NS-398, s.c. 3 mg/kg) for 1 week (n = 6) or 4 weeks (n = 6). Methacholine (endothelium-dependent dilator) and phenylephrine (adrenergic constrictor) were used to assess vascular function in the absence or presence of the nonselective PGHS inhibitor, meclofenamate (1 μmol/l) or the specific PGHS-2 inhibitor NS-398 (10 μmol/l). Results: One week of chronic PGHS-2 inhibition abolished a PGHS-dependent shift in methacholine-induced relaxation, while modulation was still observed in phenylephrine constriction. Surprisingly, 4 weeks of PGHS-2 inhibition enhanced PGHS-dependent modulation of vasoconstriction (P<0.05). PGH2/thromboxane inhibition (U-51605, 50 μmol/l) mimicked the results observed with PGHS inhibition among the groups. PGHS-2 expression increased with chronic PGHS-2 inhibition compared to control (P<0.05). Conclusions: Our data indicate a paradoxical increase in PGHS-dependent vasoconstriction and PGHS-2 expression with prolonged inhibition of PGHS-2 activity. Hence, inhibitors of PGHS-2 activity may not be beneficial in counteracting the vascular dysfunction seen with aging and menopause.
Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02
Authors: E. Q. Lee, J. Kuhn, K. R. Lamborn, L. Abrey, L. M. DeAngelis, F. Lieberman, H. I. Robins, S. M. Chang, W. K. A. Yung, J. Drappatz, M. P. Mehta, V. A. Levin, K. Aldape, J. E. Dancey, J. J. Wright, M. D. Prados, T. F. Cloughesy, M. R. Gilbert, P. Y. Wen
Journal: Neuro-Oncology (2012)

The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor-β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents.
Alpha-1-antitrypsin-Pittsburgh. A potent inhibitor of human plasma factor XIa, kallikrein, and factor XIIf.
Authors: C F Scott, R W Carrell, C B Glaser, F Kueppers, J H Lewis, R W Colman
Journal: Journal of Clinical Investigation (1986)

Alpha-1-antitrypsin-Pittsburgh is a human variant that resulted from a point mutation in the plasma protease inhibitor, alpha 1-antitrypsin (358 Met----Arg). This defect in the alpha 1-antitrypsin molecule causes it to have greatly diminished anti-elastase activity but markedly increased antithrombin activity. In this report, we demonstrate that this variant protein also has greatly increased inhibitory activity towards the arginine-specific enzymes of the contact system of plasma proteolysis (Factor XIa, kallikrein, and Factor XIIf), in contrast to normal alpha 1-antitrypsin, which has modest to no inhibitory activity towards these enzymes. We determined the second-order-inactivation rate constant (k'') of purified, human Factor XIa by purified alpha 1-antitrypsin-Pittsburgh and found it to be 5.1 X 10(5) M-1 s-1 (23 degrees C), which is a 7,700-fold increase over the k'' for Factor XIa by its major inhibitor, normal purified alpha 1-antitrypsin (i.e., 6.6 X 10(1) M-1 s-1). Human plasma kallikrein, which is poorly inhibited by alpha 1-antitrypsin (k'' = 4.2 M-1 s-1), exhibited a k'' for alpha 1-antitrypsin-Pittsburgh of 8.9 X 10(4) M-1 s-1 (a 21,000-fold increase), making it a more efficient inhibitor than either of the naturally occurring major inhibitors of kallikrein (C-1-inhibitor and alpha 2-macroglobulin). Factor XIIf, which is not inhibited by normal alpha 1-antitrypsin, displayed a k'' for alpha 1-antitrypsin-Pittsburgh of 2.5 X 10(4) M-1 s-1. This enhanced inhibitory activity is similar to the effect of alpha 1-antitrypsin-Pittsburgh that has been reported for thrombin. In addition to its potential as an anticoagulant, this recently cloned protein may prove to be clinically valuable in the management of septic shock, hereditary angioedema, or other syndromes involving activation of the surface-mediated plasma proteolytic system.
HbA1c Values Determine the Outcome of Intrasheath Injection of Triamcinolone for Diabetic Flexor Tenosynovitis
Authors: Makoto Kameyama, Osamu Funae, Shu Meguro, Yoshihito Atsumi
Journal: Diabetes Care (2006)

Stenosing flexor tenosynovitis (FTS), commonly known as “trigger finger,” is caused by a disproportion between the flexor tendon and its surrounding tendon sheath, in which smooth gliding of the flexor tendon within its sheath is restricted. First annular pulley is the most affected lesion. Intrasheath injection of triamcinolone is commonly used as an initial treatment. FTS has a reported incidence ranging from 1.7 to 2.6% in the general population (1–4). However, the incidence of FTS in diabetes is reported to be between 10 and 20% (1–3,5,6).

Diabetic FTS is not an established clinical entity. FTS with diabetes, however, is related to diabetic retinopathy (3,7,8). If FTS is regarded as a diabetes-induced complication, its clinical appearance should be related to the degree of glycemic control, the duration of diabetes, or the severity of associated diabetes complications.

Since a number of other metabolic and anatomic disorders are associated with diabetes, we considered some of these in our assessment of FTS and its response to intrasheath injection of triamcinolone.

The study comprised 179 patients with FTS (287 fingers) in diabetic conditions. Excluded patients were those with rheumatoid arthritis, gout, renal failure, and pyogenic tenosynovitis and those with a history of FTS for >1 year …
Unusual presentation of neutrophilic eccrine hidradenitis
Authors: W.J. Chng, T.P. Thamboo
Journal: British Journal of Dermatology (2004)

Journal Article Unusual presentation of neutrophilic eccrine hidradenitis Get access W.J. Chng, W.J. Chng Departments of Haematology‐Oncology and Pathology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore W.J.Chng. E‐mail: chngwj@nuh.com.sg Search for other works by this author on: Oxford Academic Google Scholar T.P. Thamboo T.P. Thamboo Departments of Haematology‐Oncology and Pathology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 2, 1 August 2004, Pages 507–508, https://doi.org/10.1111/j.1365-2133.2004.06115.x Published: 01 August 2004
Unexpected and Differential Effects of Cl <sup>−</sup> Channel Blockers on the Kv4.3 and Kv4.2 K <sup>+</sup> Channels
Authors: Hong-Sheng Wang, Jane E. Dixon, David McKinnon
Journal: Circulation Research (1997)

Abstract The Kv4.3 K + channel is thought to underlie the Ca 2+ -insensitive transient outward current ( I to1 ) in ventricular myocytes of canine and human heart and to contribute to the I to1 in rat myocytes. It has been suggested that there is a second component of the transient outward current in some species that is contributed by a Ca 2+ -activated Cl − current (known as I to2 ). The evidence for the existence of the I to2 current is based, in part, on the pharmacological effects of various Cl − channel blockers. To test for possible interactions between these compounds and I to1 , the effect of several different Cl − channel blockers on the Kv4.3 channel was examined. The fenamates (niflumic and flufenamic acid) were found to have large effects on the position of the steady state inactivation curve of the Kv4.3 channel. The disulfonic stilbenes (DIDS and SITS) had markedly different effects and were found to greatly reduce the rate of recovery from inactivation of the Kv4.3 channel without large changes in the position of the activation and steady state inactivation curves. Both classes of drugs produced an apparent blockade of the Kv4.3 channel under some recording conditions. Surprisingly, the closely related Kv4.2 channel was found to be markedly less sensitive to these drugs. Caffeine was found to block both the Kv4.3 and Kv4.2 channels to a similar extent. These nonspecific drug effects have implications for the study of the two components of the transient outward current and suggest that purely pharmacological criteria cannot be used to define the physiological role of I to2 .
Indications for Cardiac Catheterization and Intervention in Pediatric Cardiac Disease
Authors: Timothy F. Feltes, Emile Bacha, Robert H. Beekman, John P. Cheatham, Jeffrey A. Feinstein, Antoinette S. Gomes, Ziyad M. Hijazi, Frank F. Ing, Michael de Moor, W. Robert Morrow, Charles E. Mullins, Kathryn A. Taubert, Evan M. Zahn
Journal: Circulation (2011)
Pyruvate kinase deficiency confers susceptibility to <i>Salmonella typhimurium</i> infection in mice
Authors: Marie-France Roy, Noémie Riendeau, Christian Bédard, Pierre Hélie, Gundula Min-Oo, Karine Turcotte, Philippe Gros, François Canonne-Hergaux, Danielle Malo
Journal: The Journal of Experimental Medicine (2007)

The mouse response to acute Salmonella typhimurium infection is complex, and it is under the influence of several genes, as well as environmental factors. In a previous study, we identified two novel Salmonella susceptibility loci, Ity4 and Ity5, in a (AcB61 × 129S6)F2 cross. The peak logarithm of odds score associated with Ity4 maps to the region of the liver and red blood cell (RBC)–specific pyruvate kinase (Pklr) gene, which was previously shown to be mutated in AcB61. During Plasmodium chabaudi infection, the Pklr mutation protects the mice against this parasite, as indicated by improved survival and lower peak parasitemia. Given that RBC defects have previously been associated with resistance to malaria and susceptibility to Salmonella, we hypothesized that Pklr is the gene underlying Ity4 and that it confers susceptibility to acute S. typhimurium infection in mice. Using a fine mapping approach combined with complementation studies, comparative studies, and functional analysis, we show that Pklr is the gene underlying Ity4 and that it confers susceptibility to acute S. typhimurium infection in mice through its effect on the RBC turnover and iron metabolism.
Influence of general practice opening hours on delay in seeking medical attention after transient ischaemic attack (TIA) and minor stroke: prospective population based study
Authors: D. S Lasserson, A. Chandratheva, M. F Giles, D. Mant, P. M Rothwell
Journal: BMJ (2008)

<b>Objective</b> To assess the influence of general practice opening hours on healthcare seeking behaviour after transient ischaemic attack (TIA) and minor stroke and feasibility of clinical assessment within 24 hours of symptom onset. <b>Design</b> Population based prospective incidence study (Oxford vascular study). <b>Setting</b> Nine general practices in Oxfordshire. <b>Participants</b> 91 000 patients followed from 1 April 2002 to 31 March 2006. <b>Main outcome measures</b> Events that occurred overnight and at weekends (out of hours) and events that occurred during surgery hours. <b>Results</b> Among 359 patients with TIA and 434 with minor stroke, the median (interquartile range) time to call a general practitioner after an event during surgery hours was 4.0 (1.0-45.5) hours, and 68% of patients with events during surgery hours called within 24 hours of onset of symptoms. Median (interquartile range) time to call a general practitioner after events out of hours was 24.8 (9.0-54.5) hours for patients who waited to contact their registered practice compared with 1.0 (0.3-2.6) hour in those who used an emergency general practitioner service (P&lt;0.001). In patients with events out of hours who waited to see their own general practitioner, seeking attention within 24 hours was considerably less likely for events at weekends than weekdays (odds ratio 0.10, 95% confidence interval 0.05 to 0.21): 70% with events Monday to Friday, 33% on Sundays, and none on Saturdays. Thirteen patients who had events out of hours and did not seek emergency care had a recurrent stroke before they sought medical attention. A primary care centre open 8 am-8 pm seven days a week would have offered cover to 73 patients who waited until surgery hours to call their general practitioner, reducing median delay from 50.1 hours to 4.0 hours in that group and increasing those calling within 24 hours from 34% to 68%. <b>Conclusions</b> General practitioners' opening hours influence patients' healthcare seeking behaviour after TIA and minor stroke. Current opening hours can increase delay in assessment. Improved access to primary care and public education about the need for emergency care are required if the relevant targets in the national stroke strategy are to be met.
Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial
Authors: B.P. Coudert, L. Arnould, L. Moreau, P. Chollet, B. Weber, L. Vanlemmens, C. Moluçon, N. Tubiana, S. Causeret, J.-L. Misset, S. Feutray, D. Mery-Mignard, J. Garnier, P. Fumoleau
Journal: Annals of Oncology (2005)
Stroke Rates and Risk Factors in Patients Treated With Radiation Therapy for Early-Stage Breast Cancer
Authors: Reshma Jagsi, Kent A. Griffith, Todd Koelling, Rachel Roberts, Lori J. Pierce
Journal: Journal of Clinical Oncology (2006)

To examine whether stroke risk is elevated in American breast cancer patients treated with modern techniques, as well as whether supraclavicular radiation therapy (RT) is associated with increased risk.Observed rates of stroke in 820 eligible early-stage breast cancer patients treated at the University of Michigan Hospital (Ann Arbor, MI) were compared with expected rates. Relationships between potential risk factors and actuarial rate of first stroke were analyzed.Median follow-up was 6.8 years. Twenty patients had at least one cerebrovascular accident (CVA) in follow-up; 35 patients had at least one CVA or transient ischemic attack (CVA/TIA). The standardized incidence ratios were 1.74 (0.94 to 2.37) for CVA and 1.68 (1.003 to 2.06) for CVA/TIA. The absolute excess risk per 1,000 patients per year was 1.67 for CVA and 2.76 for CVA/TIA. On bivariate analysis, factors significantly associated with actuarial rate of first CVA included hypertension (P = .002), age (P < .0001), coronary artery disease (P = .001), atrial fibrillation (P = .009), and supraclavicular RT (P = .021). Factors associated with CVA/TIA were hypertension (P < .001), coronary artery disease (P = .002), and age (P < .0001). Tamoxifen use alone was not significant (P = .19), but tamoxifen combined with baseline hypertension led to increased risk of CVA/TIA (log-rank P < .0001). On multivariate analysis, only age (P < .001) and hypertension (P = .003) remained significant predictors of CVA/TIA. Age was the only significant predictor of CVA alone (P < .001).American breast cancer survivors may have an elevated risk of stroke compared with the general population, but the absolute excess risk is low. This study found no significant association between supraclavicular RT and stroke after controlling for other factors.
Consequences of Selling a Kidney in India
Authors: Prem K. G. Chandran
Journal: JAMA (2003)

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
Soundings: Tell Tchaikovsky the news
Authors: Des Spence
Journal: BMJ (2006)

Most mornings I awake to BBC Radio 4. I shouldn't because the medical stories, with their constant oversimplification of healthcare issues, set my temperature rising. Rather than blow a fuse I flick over to Virgin Radio, a station proud of its white-van-man image, but at least it occasionally plays the Jam or REM.
Natalizumab for Active Crohn's Disease
Authors: Subrata Ghosh, Eran Goldin, Fiona H. Gordon, Helmut A. Malchow, Jørgen Rask-Madsen, Paul Rutgeerts, Petr Vyhnálek, Zdena Zádorová, Tanya Palmer, Stephen Donoghue
Journal: New England Journal of Medicine (2003)

In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by α4 integrins.
Gene Therapy for Restenosis
Authors: Mary Beth DeYoung, David A. Dichek
Journal: Circulation Research (1998)

Abstract —The application of gene therapy techniques to the clinical problem of coronary restenosis has generated tremendous attention and enthusiasm. Use of gene transfer technology to prevent a common intractable illness would represent a watershed event for human gene therapy. However, the time is not yet right to initiate gene therapy trials for restenosis. The biology of restenosis is incompletely understood, catheter-based gene delivery is poorly adapted to the coronary circulation, and current gene transfer vectors are ill-suited for safe and effective gene delivery to the coronary artery wall. Basic research designed to overcome these obstacles is currently more appropriate than the initiation of clinical trials.
Disseminated <i>Ureaplasma</i> infection as a cause of fatal hyperammonemia in humans
Authors: Ankit Bharat, Scott A. Cunningham, G. R. Scott Budinger, Daniel Kreisel, Charl J. DeWet, Andrew E. Gelman, Ken Waites, Donna Crabb, Li Xiao, Sangeeta Bhorade, Namasivayam Ambalavanan, Daniel F. Dilling, Erin M. Lowery, Todd Astor, Ramsey Hachem, Alexander S. Krupnick, Malcolm M. DeCamp, Michael G. Ison, Robin Patel
Journal: Science Translational Medicine (2015)

Disseminated infection with Ureaplasma species causes fatal hyperammonemia syndrome in lung transplant recipients, likely by disrupting ammonia metabolism.
Elevated Eosinophil Protein X in Urine from Healthy Neonates Precedes Development of Atopy in the First 6 Years of Life
Authors: Bo Lund Krogsgaard Chawes, Klaus Bønnelykke, Hans Bisgaard
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Biomarkers predicting development of atopic disease are needed for targeted preventive measures and to study if disease pathology may be active before onset of symptoms.To investigate whether eosinophil protein X, leukotriene-C4/D4/E4, and 11β-prostaglandin (PG) F2α (PGD2 metabolite) assessed in urine from healthy at-risk neonates precede development of atopic disease during the first 6 years of life.We measured eosinophil protein X (n = 369), leukotriene-C4/D4/E4 (n = 367), and 11β-PGF2α (n = 366) in urine from 1-month-old children participating in the Copenhagen Prospective Studies on Asthma in Childhood birth cohort. Clinical data on development of allergic sensitization, allergic rhinitis, nasal eosinophilia, blood eosinophilia, eczema, troublesome lung symptoms (significant cough or wheeze or dyspnea), and asthma were collected prospectively until age 6 years. Associations between urinary biomarkers and development of atopic traits were investigated using general estimating equations, logistic regression, and Cox regression.Eosinophil protein X in the urine of the asymptomatic 1-month-old neonates was significantly associated with development of allergic sensitization (odds ratio, 1.49; 95% confidence interval [CI], 1.08–1.89), nasal eosinophilia (odds ratio, 3.2; 95% CI, 1.2–8.8), and eczema (hazard ratio, 1.4; 95% CI, 1.0–2.0), but not with allergic rhinitis, asthma, or blood eosinophilia. Neither leukotriene-C4/D4/E4 nor 11β-PGF2α was associated with any of the atopic phenotypes.Eosinophil protein X in urine from asymptomatic neonates is a biomarker significantly associated with later development of allergic sensitization, nasal eosinophilia, and eczema during the first 6 years of life. These findings suggest activation of eosinophil granulocytes early in life before development of atopy-related symptoms.