tbuckley/cabot-search huggingface dataset:
Combined Depletion of Cell Cycle and Transcriptional Cyclin-Dependent Kinase Activities Induces Apoptosis in Cancer Cells
Authors: Dongpo Cai, Vaughan M. Latham, Xinxin Zhang, Geoffrey I. Shapiro
Journal: Cancer Research (2006)

Abstract Selective cyclin-dependent kinase (cdk) 2 inhibition is readily compensated. However, reduced cdk2 activity may have antiproliferative effects in concert with other family members. Here, inducible RNA interference was used to codeplete cdk2 and cdk1 from NCI-H1299 non–small cell lung cancer and U2OS osteosarcoma cells, and effects were compared with those mediated by depletion of either cdk alone. Depletion of cdk2 slowed G1 progression of NCI-H1299 cells and depletion of cdk1 slowed G2-M progression in both cell lines, with associated endoreduplication in U2OS cells. However, compared with the incomplete cell cycle blocks produced by individual depletion, combined depletion had substantial consequences, with G2-M arrest predominating in NCI-H1299 cells and apoptosis the primary outcome in U2OS cells. In U2OS cells, combined depletion affected RNA polymerase II expression and phosphorylation, causing decreased expression of the antiapoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis (XIAP), effects usually mediated by inhibition of the transcriptional cdk9. These events do not occur after individual depletion of cdk2 and cdk1, suggesting that reduction of cdk2, cdk1, and RNA polymerase II activities all contribute to apoptosis in U2OS cells. The limited cell death induced by combined depletion in NCI-H1299 cells was significantly increased by codepletion of cdk9 or XIAP or by simultaneous treatment with the cdk9 inhibitor flavopiridol. These results show the potency of concomitant compromise of cell cycle and transcriptional cdk activities and may guide the selection of clinical drug candidates. (Cancer Res 2006; 66(18): 9270-80)
New Warnings Added to Cisapride Labeling
Authors: Stuart L. Nightingale
Journal: JAMA (1998)

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
A transmission line model of the normal aorta and its branches
Authors: M. B McILROY, W. S SEITZ, R. C TARGETT
Journal: Cardiovascular Research (1986)

A computer model of the aorta and its branches was made based on a simulation of an electrical transmission line using T elements. The model represented the aorta, with branches to the arms and legs and a branch to the head. The values for the capacitance and inductance of each T element could be specified, and a linearly increasing left ventricular pressure was used to drive the model. Transmission line equations were used to select values for the components, and an attempt was made to simulate the results of measurements of blood velocity in the aorta and peripheral arteries of normal subjects. The values obtained with the model showed a close relation to those in experimental studies. The results support the hypothesis that the arterial bed can be well represented by a "lossless" branched transmission line, with impedances matched at each branch and terminated with resistances that give a reflection coefficient of 0.5. A driving function, in which a linearly increasing left ventricular pressure provided a transient input to an aortic root of relatively low impedance, gave the best simulation of the experimental results.
Aid withdrawal is bringing health service in Gaza to brink of collapse
Authors: Chris McGreal
Journal: BMJ (2006)

Palestinian hospitals say that the withdrawal of foreign aid after Hamas's election victory and an Israeli partial blockade of the Gaza Strip is costing lives and driving the health service to the brink of collapse.

Doctors say that a shortage of drugs and equipment has already claimed the lives of patients, and that many hospitals are down to their last emergency supplies of drugs. The crisis has been compounded by the fact that medical staff, along with all 160 000 employees of the Palestinian Authority, have not been paid for nearly three months.

The United States said last week it is to send $10m (£5.3m; €7.8m) worth of medicines …
The Effect of Financial Incentives on Hospitals That Serve Poor Patients
Authors: Ashish K. Jha
Journal: Annals of Internal Medicine (2010)

Background: Providing financial incentives to hospitals to improve quality is increasingly common, yet its effect on hospitals that care for poor patients is largely unknown. Objective: To determine how financial incentives for quality performance affect hospitals with more poor patients compared with those with fewer poor patients. Design: Retrospective study. Setting: U.S. hospitals. Participants: 251 hospitals that participated in the Premier Hospital Quality Incentive Demonstration program and a national sample of 3017 hospitals. Measurements: The association between the disproportionate-share index, a marker of caring for poor patients, and baseline quality performance, changes in performance, and terminal performance for acute myocardial infarction, congestive heart failure, and pneumonia for hospitals in the pay-for-performance program and those in the national sample (which did not receive financial incentives). Results: Among both pay-for-performance hospitals and those in the national sample, hospitals with more poor patients had lower baseline performance than did those with fewer poor patients. A high disproportionate-share index was associated with greater improvements in performance for acute myocardial infarction and pneumonia but not for congestive heart failure, and the gains were greater among hospitals that received financial incentives than among the national sample. After 3 years, hospitals that had more poor patients and received financial incentives caught up for all 3 conditions, whereas those with more poor patients among the national sample continued to lag. Limitation: Hospitals in the Premier Hospital Quality Incentive Demonstration may be atypical, and these results may not be generalizable to all hospitals. Conclusion: No evidence indicated that financial incentives widened the gap in performance between hospitals that serve poor patients and other hospitals. Pay-for-performance programs may be a promising quality improvement strategy for hospitals that serve poor patients. Primary Funding Source: Robert Wood Johnson Foundation.
Incretin-Based Therapy and the Quest for Sustained Improvements in β-Cell Health
Authors: Daniel J. Drucker
Journal: Diabetes Care (2011)

Incretin-based therapies, principally glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, have slowly gained traction in the therapy of type 2 diabetes. DPP-4 inhibitors, which exert their activities through potentiation of endogenous GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) action (1), are well tolerated and may be combined with multiple oral agents, making them well suited for use at multiple stages in the treatment of type 2 diabetes. GLP-1R agonists require injection, and are less well tolerated due principally to gastrointestinal adverse events (nausea, and less commonly diarrhea and vomiting). Hence, like insulin, they are frequently considered for use in patients who have failed to achieve adequate glycemic control on one or more oral agents alone. However, long-acting GLP-1R agonists are more potent glucose-lowering agents compared with DPP-4 inhibitors (2), and they may produce weight loss, two major points of differentiation with meaningful clinical impact.

As the field of incretin biology gained prominence after clinical observations describing the importance of gut-derived factors in the potentiation of glucose-dependent insulin secretion, it is not surprising that the β-cell continues to be viewed as the predominant target of incretin action. Indeed, both GLP-1 and GIP robustly potentiate glucose-dependent insulin secretion in nondiabetic human subjects, and GLP-1 restores or enhances β-cell glucose sensing and insulin secretion even in diabetic patients with considerable loss of β-cell responsivity to glucose or sulfonylureas. Both GLP-1 and GIP also exhibit robust proliferative and antiapoptotic actions on rodent β-cells in experimental models of type 2 diabetes (3), and GLP-1 exerts salutary effects on the molecular mechanisms underlying β-cell function and enhances β-cell survival in studies with human islets cultured ex vivo (4,5). Hence, there has been considerable anticipation that incretin-based therapies may exert “disease-modifying” effects in type 2 diabetes through a combination of mechanisms including enhancing …
The Accessory Sinuses of the Nose, Their Surgical Anatomy and the Diagnosis and Treatment of Their Inflammatory Affections.
Authors: A. Logan Turner
Journal: JAMA (1902)

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
IgM Gammopathy and the Lupus Anticoagulant Syndrome in Habitual Aborters
Authors: Guido Finazzi
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In their recent article, Gleicher and Friberg<sup>1</sup>suggested that an IgM gammopathy may represent an integral part of circulating lupus anticoagulant syndrome (CLAS) associated with pregnancy loss. However, we observed only one case of polyclonal increase of IgM out of four patients with lupus anticoagulant and recurrent abortions. Pertinent data from our patients are summarized in the Table. In addition, we diagnosed Waldenström's macroglobulinemia in a mother of four children with lupus anticoagulant and impaired platelet function but without history of fetal loss. In this patient, immunofluorescence studies revealed platelet-bound IgG. Following elution from platelets, the IgG fraction showed lupus anticoagulant activity. Our observations indicate that IgM gammopathy is not always present in patients with the syndrome of lupus anticoagulant and recurrent abortions. Moreover, the circulating anticoagulant activity does not necessarily rest in the abnormal IgM fraction, when present. Thus, the role of IgM in the
MS-25 * GAMMA KNIFE RADIOSURGERY FOR VESTIBULAR SCHWANNOMA: ASSESSMENT OF QUALITY AND OUTCOMES
Authors: M. Straza, G. Garcia, B. Hariri, R. Patel, K. Albano, C. Schultz, D. Friedland, J. Bovi
Journal: Neuro-Oncology (2014)

OBJECTIVE: To assess and improve quality and outcomes for vestibular schwannoma cases treated with Gamma Knife radiosurgery and determine if a novel assessment of tumor and necrosis volumes correlate with outcomes. METHODS: We performed a retrospective review assessing patients with vestibular schwannoma treated with 12-13Gy from July 2009 to July 2013. A volumetric analysis was performed on a subset of patients. Pre-treatment and follow up MRIs were imported into a medical imaging software (Mimics, Materialise, Belgium). The tumor volume was computed as the volume enclosed by the tumor border, while the volume of necrosis was defined by the voxels within the tumor border that had a grayscale value smaller than the tumor segmentation threshold. RESULTS: 83 vestibular schwannomas in 83 patients were treated. 26 patients had been previously treated or lost to follow up. 57 patients were eligible for evaluation of toxicity. Median follow-up was 1.8 years. There were no documented recurrences. 49% of evaluable patients had preservation of useful hearing, Gardner Robertson Score (GRS) 1-2. Less then 5% of patients developed new vertigo, facial or trigeminal nerve complaints. Volumetric analysis of 24 patients with median follow up of 3.1 years revealed larger median necrosis volumes to be associated with a worse GRS, with necrosis volumes decreasing over time in patients with preserved hearing. Patients without vertigo at last follow up had smaller volumes of necrosis that also decreased over time. CONCLUSION: Our institution's experience with gamma knife radiosurgery for vestibular schwannoma demonstrates tumor control and toxicity results similar to previously published series. Prior studies on gamma knife radiosurgery for these tumors have correlated toxicity with tumor size, radiation dosage, and tumor location. Our novel approach for assessment of tumor and necrosis volumes may provide a new tool for predicting functional outcomes and merits further study.
Toward a System of Emergency Medical Care
Authors: Bette Kough Noble
Journal: New England Journal of Medicine (1976)

A previous column1 traced the impetus for a program to improve the quality of emergency medical care in Massachusetts. Co-ordinated by the Department's Office of Emergency Medical Services, the program's objectives are to upgrade resources of personnel and equipment in the pre-hospital and hospital sectors and to establish co-ordinated systems of care that meet local needs but are consistent with statewide minimum standards. Some of the progress to date merits consideration: the acquisition of modern equipment; the training of personnel who deliver care at the scene of an emergency, en route to the hospital, and in the emergency ward; and . . .
Gastric Crohnʼs Disease Detected by Tc-99m HMPAO Mixed Leukocyte Scan
Authors: ENRIQUE PRATS, JAVIER BANZO, MARIA D. ABOS OLIVARES, EMILIO FREILE
Journal: Clinical Nuclear Medicine (1994)

Gastric Involvement in Crohn's disease, though uncommon, is being increasingly recognized and occurs in 1–4% of patients. Upper abdominal pain, weight loss, nausea, and vomiting are the predominant clinical symptoms. In most cases, the gastric involvement consists of mild changes seen by endoscopy and is established only by means of histologic examination of biopsy material. Radiologic findings are therefore frequently absent or minimal. Tc-99m HMPAO labeled leukocyte scan can be useful in the simultaneous demonstration of gastric and intestinal affectation in Crohn's disease.
Response to Letter Regarding Article, “Lipoprotein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)”
Authors: Amit V. Khera, Brendan M. Everett, Michael P. Caulfield, Feras M. Hantash, Jay Wohlgemuth, Paul M Ridker, Samia Mora
Journal: Circulation (2014)
Abstract 2254: A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes.
Authors: Corey Levenson, Erik R. Olson, David S. Alberts, G. Tim Bowden
Journal: Cancer Research (2013)

Abstract α-Santalol, one of the primary components of the East Indian sandalwood oil (EISO), has been investigated for its potential use as a chemopreventive agent in skin cancer. Although there is some evidence that α-santalol could be an effective chemopreventive agent, to date, purified EISO has not been investigated. EISO is widely used for its health benefits in cultures around the world. In the current study, we show for the first time that EISO-treatment of cultured keratinocytes inhibits cell cycle progression and UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, inhibition of signaling upstream of AP-1 was not a primary means of EISO-mediated AP-1 inhibition, as no effect of EISO was observed on UV-induced Akt, ERK, and p38 MAPK activity. EISO induced cell death at low concentrations, although caspase and PARP cleavage were not observed indicating that death was not due to apoptosis. Interestingly, plasma membrane integrity was severely compromised in EISO-treated cells and LC3 cleavage suggests the induction of autophagy. These effects were more pronounced in EISO-treated cells that were stimulated to proliferate than in quiescent cells. Together, these effects suggest that EISO has chemopreventive properties and may be useful as in preventing skin carcinogenesis. Citation Format: Corey Levenson, Erik R. Olson, David S. Alberts, G. Tim Bowden. A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2254. doi:10.1158/1538-7445.AM2013-2254
Distinguishing direct and indirect inguinal hernias.
Authors: W M Beattie
Journal: BMJ (1980)

The paper by Giacchino and his colleagues,7 on which your recommendations for manage- ment are so clearly based, was criticised in the subsequent discussion for its conclusions that colonoscopy should not be performed and it is surprising that you should perpetuate this erroneous conclusion.There is clearly much evidence to support a co-ordinated approach to the problem of massive bleeding from the large bowel, involving the gastroenterologist, endoscopist, radiologist, and surgeon in a joint and flexible approach to investigation and management rather than adherence to the more rigid flow chart suggested.
Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period
Authors: X Thomas, C Danaïla, Q-H Le, C Sebban, J Troncy, C Charrin, V Lhéritier, M Michallet, J-P Magaud, D Fiere
Journal: Leukemia (2001)
Commentary: Living with CFS/ME
Authors: O. Cornes
Journal: BMJ (2011)

During my career I have co-written several books on computer software, worked as a software engineer, and set up and sold two small technology businesses. But in April 1999 I developed tonsillitis with its usual malaise and fatigue. I naturally assumed I would be back to health fairly quickly, but, although the tonsillitis cleared, the malaise and low energy levels persisted. I felt like I was running on fumes. I had no idea why. Then my health deteriorated further.

Months passed, then a year, and now 12 years. I have occasional periods when I’m bed bound, and I am often house bound. I’m always exhausted. I often move around at home like a frail, unstable, elderly man—at the age of 38. It’s certainly made worse by my not knowing what is causing it.

My general practitioner, and many books, suggested the illness was in some way psychosomatic (“yuppie flu,” not a proper illness). I knew in myself this wasn’t true, but there was a nagging doubt. Maybe …
Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis
Authors: Hirokazu Hirata, Atsushi Takahashi, Susumu Kobayashi, Shin Yonehara, Hirofumi Sawai, Toshiro Okazaki, Kokichi Yamamoto, Masataka Sasada
Journal: The Journal of Experimental Medicine (1998)

Two novel synthetic tetrapeptides, VEID-CHO and DMQD-CHO, could selectively inhibit caspase-6 and caspase-3, respectively. We used these inhibitors to dissect the pathway of caspase activation in Fas-stimulated Jurkat cells and identify the roles of each active caspase in apoptotic processes. Affinity labeling techniques revealed a branched protease cascade in which caspase-8 activates caspase-3 and -7, and caspase-3, in turn, activates caspase-6. Both caspase-6 and -3 have major roles in nuclear apoptosis. Caspase-6 cleaves nuclear mitotic apparatus protein (NuMA) and mediates the shrinkage and fragmentation of nuclei. Caspase-3 cleaves NuMA at sites distinct from caspase-6, and mediates DNA fragmentation and chromatin condensation. It is also involved in extranuclear apoptotic events: cleavage of PAK2, formation of apoptotic bodies, and exposure of phosphatidylserine on the cell surface. In contrast, a caspase(s) distinct from caspase-3 or -6 mediates the disruption of mitochondrial membrane potential (permeability transition) and the shrinkage of cytoplasm. These findings demonstrate that caspases are organized in a protease cascade, and that each activated caspase plays a distinct role(s) in the execution of Fas-induced cell death.
The Health Manpower Gap Re-Examined
Authors: Victor R. Fuchs, Elizabeth H. Rand, Bonnie Garrett
Journal: New England Journal of Medicine (1970)

THE difficulty the United States is now experiencing in delivering adequate medical care to the total population has been attributed to a "doctor shortage," but it may also be related to the extraordinary discontinuity in the skill distribution of personnel in the health industry.Using annual earnings of full-time workers as an index of the skill, ability, motivation and other qualities that a worker brings to a job, we have compared the distribution of earnings in health with that in nineteen other large industries.* Mean earnings in health (including earnings of nurses, secretaries, orderlies and all other persons employed in . . .