tbuckley/cabot-search huggingface dataset:
672. Lentiviral Transduction of INK4A/ARF Protein Cooperates with Anti-Leukemic Agents To Induce Apoptosis of Leukemia Cells
Authors: Yuansong Bai, Yasushi Soda, Minghan Chen, Kiyoko Izawa, Seiichiro Kobayashi, Akira Tomonari, Jun Ooi, Fumitaka Nagamura, Satoshi Takahashi, Kaoru Uchimaru, Tohru Iseki, Hiroyuki Miyoshi, Tsuneo A. Takahashi, Kenzaburo Tani, Arinobu Tojo, Shigetaka Asano
Journal: Molecular Therapy (2004)

Inactivation of the INK4A/ARF locus has been implicated in tumorigenesis, particularly in leukemogenesis. It has been found in 25–60% cases of acute leukemia and 20–50% cases of lymphoma. Although deletion of the INK4A/ARF locus is uncommon in AML, mRNA expression is likely to be disrupted, resulting from hypermethylation or mutation in the promoter region. There is some evidence that restoration of p16INK4a into p16-deficient leukemia cell lines suppresses their proliferation in suspension culture or their clonogenic growth in semisolid culture. However, previous studies were conducted by retrovirus or plasmid-mediated gene transfer under drug selection, suggesting low efficiency of transduction which appears disadvantageous to interpret the results of the growth inhibitory gene. Here we constructed a lentiviral vector expressing either p16ink4a or p14arf respectively, and validated its effect on leukemia cells, especially in combination with anti-leukemia agents including imatinib, ATRA and TNF-α. The p16, p14, hrGFP or mock lentiviral transfer vector was introduced into 293T cells along with packaging plasmids (pMDLg/p.RRE and pMD.G) and pRSV-Rev. The resulting VSV-G-pseudotyped lentivirus supernatant was concentrated by ultracentrifugation for high-titer virus stock. K562, NB4 and IMS-M2 cells were infected with those prepared viruses at the multiplicity of infection (moi) of 20–50, which allowed almost 100% of infection efficiency based on hrGFP fluorescence. The former two cell lines were deficient in p16 and p14 transcripts and had mutated p53 but intact pRb, while the latter one expressed both transcripts and had mutated p53 but intact pRb. Overexpression of p16 induced leukemia cells to accumulate in the G1 phase, followed by partial (IMS-M2) or complete (K562 and NB4) inhibition of cell growth. In addition, overexpression of p14 resulted in partial (IMS-M2) or substantial (K562 and NB4) apoptotic cell death, suggesting the presence of p53-independent pathway of apoptosis through p14. Next, we transduced p16 and p14 in primary blast cells from CML-BC or AML patients, resulting in their growth inhibition and apoptosis with a patient to patient variation. On the other hand, clonal growth and differentiation of cord blood progenitor cells was not affected by enforced expression of either p16 or p14 at the same moi. Next, not only imatinib and TNF-α-induced apoptosis of K562 and IMS-M2 cells but also ATRA-induced apoptosis of NB4 cells were markedly enhanced by transduction of p14 at a low moi less than 2.5. These results suggest that INK4A/ARF protein-mimetic agents may be promising options for leukemia in combination with the present anti-leukemia agents since these diseases are relatively resistant to a single agent.
Abstract 20047: Nasa Model of "Threat and Error" in Paediatric Cardiac Surgery: Death Typically Results From Cycles of Error That Originate in the Operating Room and Are Amplified by Additional Error in Intensive Care
Authors: Edward Hickey, Yaroslavna Nosikova, Eric Pham-Hung, Michael Gritti, Travis Wilder, Sara Hussain, Christopher A Caldarone, Steven Schwartz, Andrew Redington, Glen S Van Arsdell
Journal: Circulation (2014)

Introduction: We introduced the NASA “threat and error model” to our surgical unit; all admissions are considered “flights”, which should pass through stepwise de-escalations in risk. Hypothesis: Errors significantly influence risk de-escalation and contribute to poor outcomes. Methods: Patient flights (524) were tracked real-time for threats, errors and unintended states (figure). Expected risk de-escalation was: wean from mechanical support, sternal closure, extubation, ICU discharge and discharge home. Data were accrued via performance personnel, bedside data, reporting mechanisms and staff interviews. Infographics of flights were openly discussed weekly. Results: In 12% (64/524) of flights, the child failed to de-escalate sequentially through expected risk levels; unintended increments instead occurred. Failed de-escalations were highly associated with errors (426; 257 flights), however seemingly benign (P&lt;.0001). Errors with clinical consequence (263; 173 flights) had 29% rate of failed de-escalations vs 4% (P&lt;.0001). The most dangerous errors were “apical” errors typically (84%) occurring in the OR which led to cycles of propagating unintended states (n=110): these had 43% (47/110) rate of failed de-escalation (vs 4%, P&lt;.0001). Apical errors were triggered by identifiable threats in 25% (28/110) (usually - 75% - morphology/ comorbidities); 75% were instead “unforced” errors. Cycles of unintended state were often (46%) amplified by additional (up to 7) errors in ICU that would worsen clinical deviation. Overall, failed de-escalations in risk were extremely closely linked to brain injury (N=13; P&lt;.0001), or death (N=7; P&lt;.0001). Conclusions: Deaths and brain injury almost always occur from propagating error cycles that originate in the OR and are often amplified by additional ICU errors. Improvements in threat management, error detection/rescue and vigilance at times of failed de-escalation will translate into improved outcomes.
When I use a word . . . : The venereal game
Authors: J. Aronson
Journal: BMJ (1998)

We all know that a group of lions is called a pride, of geese a gaggle, and of cows a herd. The game of inventing words to describe assemblages of animals or human beings is over 500 years old. The earliest collections of such terms are to be found in The Egerton Manuscript (1450) and, more definitively, The Boke of St Albans (1486), a collection written by Dame Juliana Berners. The modern source books for this information are An Exaltation of Larks by James …
Long-term Outcomes of Lyme Disease
Authors: Virginia T. Sherr
Journal: JAMA (2000)

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
Commentary: Change will not happen overnight
Authors: A Griekspoor, D Nabarro, A Loretti, I Smith
Journal: BMJ (2005)

but not a devastating disaster that compounds with profound vulnerability and leaves massive death and destruction in its wake.Contributors and sources: PW worked for 20 years in disaster management and policy development for several international non-governmental organisations and the Red Cross before his current post.BW has written extensively over the past 30 years on natural disaster management and mega-city disasters.JL lectures on disasters, public health, and human rights at Harvard School of Public Health and has recently completed a mission to the Chad-Darfur border evaluating the aid effort there.LM has extensive experience in analysing
S100A8/A9 deficiency in nonhealing venous leg ulcers uncovered by multiplexed antibody microarray profiling
Authors: H. Trøstrup, R. Lundquist, L.H. Christensen, L.N. Jorgensen, T. Karlsmark, B.B. Haab, M.S. Ågren
Journal: British Journal of Dermatology (2011)

Knowledge on the underlying mechanisms for nonhealing chronic wounds is fragmentary.To increase our understanding of the pathogenesis, the relationship between healing ability and a large panel of proteins was studied using a specially designed wound-healing antibody-based microarray.Wound fluid from nondiabetic patients with nonhealing venous leg ulcers was compared with that from patients with healing open granulating acute wounds. The high-throughput method enabled simultaneous measurement of the relative levels of 48 different proteins representing major categories of wound-healing modulators.Unexpectedly, several of the examined proteins, including various proinflammatory cytokines, proteinases and antiproteinases, were not significantly (P>0·001) changed in chronic wound fluid. For example, levels of matrix metalloproteinase-9 and one of its substrates type IV collagen were similar in the two groups. The wound fluid samples displayed similar degrees of fragmentation of fibronectin by Western blot analysis and the total fibronectin levels were doubled (P<0·001) in chronic compared with acute wounds. The increased fibronectin originated from α-smooth muscle actin-positive myofibroblasts and not from the circulation. S100A8/A9 was the sole protein that was reduced (P<0·001) in wound fluid from venous ulcers [median 226 μg mL(-1) (interquartile range 213-278)] compared with healing wounds [455 μg mL(-1) (382-504)], probably reflecting a difference in inflammatory cell composition.The molecular anomalies in chronic wounds are more subtle than the current paradigm and neither excessive proteinase activity nor deficiencies of examined extracellular matrix proteins, growth factors or angiogenic/angiostatic factors appear to contribute significantly to the nonhealing state of venous leg ulcers.
Experimental Tumor Induction in a Circumscribed Region of the Hamster Trachea: Correlation of Histology and Exfoliative Cytology2
Authors: Hans Schreiber, Karin Schreiber, Donald H. Martin
Journal: JNCI Journal of the National Cancer Institute (1975)

A method for the induction of carcinomas in a circumscribed region of the hamster trachea is reported. By means of a special catheter, a solution of N-nitroso-N-methylurea was applied twice a week to about a 6-mm length of the trachea 10- to 16-mm distal from teh vocal cords. Slight alteration of this catheter allowed sampling of cytologic specimens directly from the surface of the carcinogen0exposed epithelium. This procedure permitted the simple and accurate correlation of sequential histologic and cytologic changes observed during tumor development in the hamsters. Noninvasive dysplastic and metaplastic lesions were seen in animals killed after 5 and 10 weeks of carcinogen application. These epithelial changes could be readily correlated with abnormal exfoliated cells abundantly present in cytologic specimens from these animals. Exposure to carcinogen for 15 weeks induced a 100% tumor incidence exclusively at the application site. More than 75% of the malignancies appeared within 15-20 weeks after the start of carcinogen administration. Most tumors were epidermoid carcinomas but some anaplastic large-cell carcinomas were also observed. Cytologic specimens of tumor-bearing animals had many cells conclusive of malignancy. The new experimental system lends itself to study of the effect of topically applied anticarcinogenic or cocarcinogenic agents on different carcinogen-induced epithelial lesions whose regression or progression can be followed by exfoliative cytology.
Abstract 1606: Global mapping of tyrosine kinase signalling in breast cancer by combined use of RNAi and SILAC quantitative proteomics
Authors: Hua Zhang, Justin Stebbing, Yichen Xu, Georgios Giamas
Journal: Cancer Research (2014)

Abstract Dysregulation of protein tyrosine kinases (TKs) signalling can contribute to tumorigenesis. However, less than half of the 90 TKs described so far have been thoroughly studied and even in these cases a global functional analysis is still lacking. A combined use of RNA interference (RNAi) and stable isotope labelling by amino acids in cell culture (SILAC) was applied in breast cancer MCF7 cells. After knocking down individually each TK, a proteomic map consisting of ∼3,000 regulated proteins per TK was acquired. Quantitative and statistical analyses resulted in the clustering of the significantly modulated proteins/TK into various biological and molecular categories. Further use of mathematical modelling tools resulted in a new classification and phylogeny of the TK family members depending on connections between their regulated proteomes. This taxonomy has little overall correlation when compared to their catalytic domain sequence grouping. These data suggest that despite the primary structure homology of kinases, their regulated proteomic landscapes can significantly vary and may depend on other factors, notably their dynamic interactions with other proteins. Our results and bionformatic analyses will be presented. Citation Format: Hua Zhang, Justin Stebbing, Yichen Xu, Georgios Giamas. Global mapping of tyrosine kinase signalling in breast cancer by combined use of RNAi and SILAC quantitative proteomics. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1606. doi:10.1158/1538-7445.AM2014-1606
381. Self-Cleaving Multimeric Hammerhead Ribozymes Abolish Mutant Collagen Transcripts In Cellulo and Exhibit Activity In Vivo
Authors: Daniel P. Reay, Roberto Bilbao, Eric Wu, Terry L. O'Day, Jon F. Watchko, Paula R. Clemens
Journal: Molecular Therapy (2004)

Current progress in adenoviral (Ad) gene therapy for Duchenne muscular dystrophy (DMD), a degenerative, inherited neuromuscular disease characterized by a lack of a functional dystrophin protein, has revealed many physical and biochemical obstacles affecting the transduction of muscle. To avoid barriers such as the basal lamina surrounding each muscle fiber and a mature immune system, fetal gene therapy could be an attractive method to deliver therapeutic genes to afflicted individuals. The ability to use a small vector load to transduce target organs in utero, combined with the possibility of transducing progenitor or stem cells, provides a key advantage over post-natal treatment. High-capacity Ad (HC-Ad) vectors devoid of all viral genes have shown more persistent expression after transduction in utero, as compared to first-generation Ad vectors, and have the added ability to carry the full-length 14 kb murine or human dystrophin cDNA. In a previous transduction study in C57BL/6 mice in utero, transgene expression was stable for at least 5 months by intramuscular injection. Furthermore, a lack of neutralizing antibody response to the Ad vector in injected animals was observed, which may allow for repeat administration of vector later in life. For this study we wanted to determine if a single intramuscular in utero injection of an HC-Ad vector carrying the full-length murine dystrophin cDNA could ameliorate the dystrophic phenotype, restore the dystrophin-glycoprotein complex, and provide functional correction of transduced muscles in the mdx mouse, an animal model for DMD. Using a surgical approach on pregnant mdx mice carrying embryonic gestation day 16 fetuses (E-16), one hind limb of fetal mice was injected with an HC-Ad vector carrying dystrophin. The injected pups were delivered naturally and analyzed at 9 weeks of age. In vitro physiological studies showed modest functional correction as assessed by specific tetanic force and muscle weight in an in utero transduced tibialis anterior muscle demonstrating recombinant dystrophin expression. Furthermore, the dystrophin-glycoprotein complex was restored in those fibers expressing dystrophin. These studies provide the first evidence that dystrophin gene delivery in utero has the potential for therapeutic effect in DMD.
Abstract 15259: Impact of Tissue Heterogeneity of Hematoma on the Development of Ulcer-like Projection in Patients With Acute Aortic Intramural Hematoma
Authors: Takeshi Kitai, Shuichiro Kaji, Kitae Kim, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Tomoko Tani, Yutaka Furukawa
Journal: Circulation (2014)

Background:  Ulcer-like Projection (ULP) has been currently recognized as a maker of progressive disease course in patients with acute aortic intramural hematoma (IMH). Although precise mechanism of ULP development is still unclear, micro flow via small intimal tear may be one of the causes. This study aimed to investigate whether computed tomography (CT) density values of thickened aortic wall could predict development of ULP.   Methods:  We studied 35 patients (age; 72±11 years, male/female; 21/14) who were admitted to our institution due to IMH within 48 hours from the onset, and underwent serial 64-row multi-slice CT examinations. CT density values were assessed on admission within thickened aortic wall in each slice at aortic arch, proximal descending aorta, mid descending aorta, and distal descending aorta (Figure). We calculated heterogeneity index as standard deviation of CT values divided by mean values. Development of ULP, defined as a localized blood-filled pouch protruding into the thrombosed false lumen, was assessed by comparing the initial and follow-up CT within 30 days from the onset.   Results:  The development of ULP was observed in 15 patients (43%), whereas 20 patients (57%) showed significant regression of thickened aortic wall. Patients who developed ULP had significantly higher heterogeneity index (0.36±0.11 vs 0.26±0.07, P=0.002), although there were no significant differences in mean CT values between patients with and without ULP (51.7 vs 53.1, P=0.69). Moreover, receiver-operating characteristic curve analysis identified CT heterogeneity index of 0.29 as a cut off for predicting ULP development (area under the curve, 0.79; 95% CI, 0.64-0.94, P=0.003) with sensitivity and specificity of 80% and 75%, respectively.   Conclusions:  Evaluation of tissue heterogeneity of hematoma assessed by CT density values might be useful to predict disease progression in patients with IMH.
Plague Rapid Diagnostic Test
Authors: Joan Stephenson
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
Abstract 17050: Association of Kidney Dysfunction with Chronotropic Incompetence in Heart Failure with Preserved Ejection Fraction
Authors: David A Klein, Daniel H Katz, Lauren Beussink-Nelson, Theresa A Strzelczyk, Sanjiv J Shah
Journal: Circulation (2014)

Introduction: Chronotropic incompetence (CI) is an important pathophysiologic factor underlying reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF), but clinical factors associated with CI in HFpEF are unknown. Based on anecdotal clinical experience, we hypothesized that coronary artery disease (CAD) and chronic kidney disease (CKD) are associated with CI in HFpEF. Methods: We studied 157 consecutive HFpEF patients undergoing cardiopulmonary exercise testing, and defined CI as maximal heart rate (HR) &lt; 80% of estimated HR reserve (&lt; 65% if using beta-blockers). Participants who achieved inadequate exercise effort (respiratory exchange ratio [RER] ≤ 1.05) were excluded. Unadjusted and multivariable-adjusted regression models were used to determine correlates of CI. Results were re-assessed using alternative formulations of chronotropic response. Results: Of 157 participants, 73% were women, 64% used beta-blockers, 32% had CKD, and 40% had CAD. RER &gt; 1.05 was achieved by 108 (69%) participants, including 79/108 (76%) with CI. Lower estimated GFR, higher B-type natriuretic peptide, and higher pulmonary artery systolic pressure (but not CAD) were each associated with CI. A 1-SD decrease in GFR was independently associated with CI (adjusted odds ratio = 2.4, 95% confidence interval = [1.3, 4.6]) after adjustment for smoking status, log BNP, and beta blocker usage. Linear regression models demonstrated that GFR was independently and linearly associated with %HR reserve (β=0.31, SE=0.10; P=0.002; Figure). Findings were unchanged after re-calculation of %HR reserve and CI based on alternative formulations used in the literature. Conclusions: CI is common and strongly associated with GFR in HFpEF. Our results indicate that kidney function may mark or contribute to the development of CI in HFpEF. HFpEF patients with CKD may need to be screened for CI prior to starting medications (e.g., beta blockers) that could exacerbate CI.