tbuckley/cabot-search huggingface dataset:
Abstract 3435: Targeting AKT activity inhibits MYCN and sensitizes neuroblastoma to chemotherapeutic agents
Authors: Marion Le Grand, Kathleen Kimpton, Christine Gana, Emanuele Valli, Chelsea Mayoh, Maria Kavallaris
Journal: Cancer Research (2019)

Abstract MYCN-amplified neuroblastoma is one of the deadliest forms of childhood cancer and remains a significant clinical problem. Direct pharmacological inhibition of MYCN protein is challenging and one possible strategy to treat MYCN-amplified neuroblastoma patients is antagonizing proteins involved in its regulation. The AKT/GSK3β pathway directly regulates stabilization of MYCN, providing a therapeutic rational in MYCN-amplified neuroblastoma. In this study, we addressed the question of how AKT can play a pivotal role in MYCN-amplified neuroblastoma and whether small molecule AKT inhibitors can be promising anti-cancer compounds in children diagnosed from this cancer. Bioinformatics analysis revealed that high gene expression of AKT1 and AKT2, but not AKT3 was correlated with MYCN amplification and was significantly associated with poor outcome in neuroblastoma patients. Using RNAi-mediated depletion of AKT isoforms or pharmacological inhibition, we then demonstrated that the total AKT activity inhibition rather than the expression of particular isoforms was necessary to cause a significant decrease in neuroblastoma cell proliferation. Our results showed that AKT activity inhibition led to a significant downregulation of MYCN expression through GSK3β regulation. These results demonstrated the potential of targeting AKT activity in MYCN-amplified neuroblastoma patients. Our in vitro and in vivo data revealed promising efficacy for the pan-AKT inhibitor perifosine combined with conventional cytotoxic drugs in MYCN-amplified neuroblastoma cell. Importantly, by genetically modulating MYCN expression (siRNA or plasmid vector), our results demonstrated that MYCN expression is required for perifosine chemosensitisation. This effect was linked to the combined actions of apoptosis activation and the downregulation of ABC transporter expressions. Collectively, our data strongly support that combining the pan-AKT inhibitor perifosine, which is currently in clinical trial, with clinically-approved drugs for neuroblastoma patients could be a novel therapeutic strategy to indirectly target MYCN in neuroblastoma. Citation Format: Marion Le Grand, Kathleen Kimpton, Christine Gana, Emanuele Valli, Chelsea Mayoh, Maria Kavallaris. Targeting AKT activity inhibits MYCN and sensitizes neuroblastoma to chemotherapeutic agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3435.
Marine Swimming-Related Illness: Implications for Monitoring and Environmental Policy
Authors: Sarah E. Henrickson, Thomas Wong, Paul Allen, Tim Ford, Paul R. Epstein
Journal: Environmental Health Perspectives (2001)

There is increasing evidence that environmental degradation may be contributing to an increase in marine-related diseases across a wide range of taxonomic groups. This includes a growing number of reports of both recreational and occupational users of marine waters developing gastrointestinal, respiratory, dermatologic, and ear, nose, and throat infections. The duration and type of exposure, concentration of pathogens, and host immunity determine the risk of infection. Public health authorities may not be able to accurately predict the risk of waterborne disease from marine waters due to the limitations of conventional monitoring, as well as erroneous perceptions of pathogen life span in marine systems. Pathogens undetectable by conventional methods may remain viable in marine waters, and both plankton and marine sediments may serve as reservoirs for pathogenic organisms, which can emerge to become infective when conditions are favorable. In this paper we address the environmental factors that may contribute to illness, the types of associated economic costs, the issues of water quality monitoring and the policy implications raised by the apparent rise in incidence of marine water-related illnesses.
Association News
Journal: JAMA (1907)

<h3>NEW MEMBERS.</h3> List of new members of the American Medical Association for the month of October, 1907: ALABAMA. Blackburn, C. B., Fayette. Maumenee, A. E., Mobile. Nicholls, A. B. C., Tuscaloosa. Scott, E. M., Avondale. ARKANSAS. Adams, R. J., Morrilton. Burns, R. P., Bradley. Edwards, D. H., El Paso. Graham, M. C., Gainesville. Hunt, W. R., Clarksville. Johnson, J. J., Biggars. King, J. H. C., Hot Springs. Kolb, J. S., Clarksville. Kosminsky, L. J., Texarkana. McAdams, J. C., Judsonia. McLaughlin, J. A., Ft. Smith, Mock, W. H., Prairie Grove. Pearson, M. L., Poplar Grove. Roe, J. B., Calico Rock. Routh, C. M., Batavia. Smith, H. H., Calico Rock. Young, J. L., Jenny Lind. Zeli, A. M., Little Rock. CALIFORNIA. Bettola, Mariana, San Francisco. Bluhm, G. L, San Francisco. Cadwallader, R., San Francisco. Clark. F. P., Stockton. Dewitt, J. W., Antioch. Fischer, M. H., Livermore. Forrest, R. A., Occidental. Foshay, A. W., Oakland.
Editorial Board
Authors: James Field, Samuel Soskin, Beverly Hills, Garfield Duncan, Salman Azhar, Palo Alto, Hisham Barakat, George Bray, Jorge Calles-Escandon, José Caro, M Charles, San Francisco, George Chrousos, Bernard Bethesda, St Davis, Leslie Louis, Frederick Degroot, Mario Derubertis, Atlanta Digirolamo, William Ga, Louis Duckworth, John Elsas, Kenneth Fain, San Feingold, Andrew Francisco, New Frantz, Gregory York, Saul Freund, Henry Cleveland, New Ginsberg, Charles York, Jane Glueck, Abbas Cleveland, Fredric Kitabchi, Stanford Kraemer, Nelly Mauras, James May, Donald Mcnamara, Glenn Mortimore, Maria New, New York, Michael Pagliassotti, Ft Collins, William Pandak, Alan Richmond, Los Robinson, Stanton Angeles, Peter Segal, Richard Stacpoole, Marc Durham, John Tucson
Journal: Metabolism (2007)
Prognostic value of contralateral renal plasma flow in renovascular hypertension. Analysis of 55 surgically treated patients with proved unilateral lesions
Authors: J. M. Palmer
Journal: JAMA (1971)

Seventy-one hypertensive patients underwent differential renal function studies with use of urea,<i>p</i>-aminohippurate inulin infusion. All had surgery and 55 had proved unilateral renovascular cause for high blood pressure. Of these, 21 were cured, 20 were improved, and 14 were not affected by the surgical procedures. Cured patients had a mean renal plasma flow (RPF) to the contralateral kidney of 312 ± 24 ml/min. The value was 285 ± 19 ml/min for improved patients and 217 ± 20 ml/min for patients unchanged by surgery. The mean contralateral RPF for cured and improved patients differed significantly (<i>P</i>= 0.01) from that of the failure patients. These differences remained significant when calculated for atherosclerotic patients alone. Although overlap was present, these data will aid in exclusion of atherosclerotic patients of doubtful prognosis from low-yield renovascular surgical procedures.
Manuscripts Approved for JNCI, February–March 1975
Journal: JNCI Journal of the National Cancer Institute (1975)

Manuscripts Approved for JNCI, February–March 1975 Get access JNCI: Journal of the National Cancer Institute, Volume 54, Issue 4, April 1975, Page 1017, https://doi.org/10.1093/jnci/54.4.1017-a Published: 01 April 1975
Incorrect Value
Journal: JAMA (1984)

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
First immunotoxin therapy for many common solid tumors enters phase I clinical trial
Authors: A. A. Skolnick
Journal: JAMA (1993)

THE FIRST clinical trial of an immunotoxin that is genetically engineered to target a variety of common solid tumors is under way at the National Cancer Institute (NCI), Bethesda, Md. The phase I trial, which began in April, involves patients with breast or colon cancers that do not respond to conventional therapies. Ira Pastan, MD, chief of the NCI's Laboratory of Molecular Biology and coinventor of the immunotoxin, described the development of this new type of anticancer agent at a conference in Chicago, Ill. The conference, DNA: The Double Helix— Forty Years: Perspective and Prospective, was cosponsored by The New York (NY) Academy of Sciences, The University of Illinois at Chicago, and Green College, Oxford University, England. So far only seven of the 20 to 30 patients Pastan hopes to enroll in the trial have been treated with a protocol for determining the toxic effects of his experimental drug, B3-LysPE38.
Role of nitric oxide in the synthesis of guanidinosuccinic acid, an activator of the N-methyl- d-aspartate receptor
Authors: Kazumasa Aoyagi, Siranoush Shahrzad, Satomi Iida, Chie Tomida, Aki Hirayama, Sohji Nagase, Katsumi Takemura, Akio Koyama, Shoji Ohba, Mitsuharu Narita, Burton D. Cohen
Journal: Kidney International (2001)
Real-Time Three-Dimensional Echocardiographic Study of Left Ventricular Function After Infarct Exclusion Surgery for Ischemic Cardiomyopathy
Authors: Jian Xin Qin, Takahiro Shiota, Patrick M. McCarthy, Michael S. Firstenberg, Neil L. Greenberg, Hiroyuki Tsujino, Fabrice Bauer, Agnese Travaglini, Kathy J. Hoercher, Tiffany Buda, Nicholas G. Smedira, James D. Thomas
Journal: Circulation (2000)

Background —Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. Methods and Results —Thirty patients who underwent IE (mean age 61±8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42±67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99±40, 67±26, and 71±31 mL/m 2 , respectively; ESVI 72±37, 40±21, and 42±22 mL/m 2 , respectively; P &lt;0.05). LV ejection fraction increased significantly and remained higher (0.29±0.11, 0.43±0.13, and 0.42±0.09, respectively, P &lt;0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22±12, 53±24, and 58±21 mL, respectively, P &lt;0.005). New York Heart Association functional class at an average 285±144 days of clinical follow-up significantly improved from 3.0±0.8 to 1.8±0.8 ( P &lt;0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman’s ρ=0.58 and 0.60, respectively). Conclusions —RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.
Stapling machines.
Journal: BMJ (1966)

Before the " hyperdynamic beta-adrenergic circulatory state " is allowed to emerge as a new entity it should be separated more clearly from the more familiar anxiety state, and observations of proved value such as the sleeping pulse rate and the response of the blood pressure and pulse rate to sedation should be recorded.However, these cases, and other published reports3 I to which Frohlich and his colleagues draw attention, indicate that further investigation might yield useful information about some sinus tachycardias and modify the rationale of their management.
Abstract 2965: Mutations in <i>SNTA1-</i> Encoded Syntrophin α: Characterization of a Novel Long QT Syndrome Susceptibility Gene Involving the Sodium Channel Macromolecular Complex
Authors: Argelia Medeiros-Domingo, Carmen Valdivia, Matteo Vatta, Gianrico Farrugia, Jonathan C Makielski, Michael J Ackerman
Journal: Circulation (2007)

Background: Genes encoding sodium channel interacting proteins (ChIPs) have been identified as novel long QT syndrome (LQTS)-susceptibility genes. Approximately 25% of patients with LQTS remain genotype negative. ChIPs comprising the sodium channel macromolecular complex represent attractive candidates for disease susceptibility. Previously, in human jejunal circular smooth muscle, we demonstrated that syntrophin γ2 regulates sodium channel gating by a PDZ-domain interaction involving the C-terminus. In the heart, syntrophin α is more highly expressed than γ2, therefore, syntrophin α was evaluated as a possible LQTS-susceptibility ChIP. Methods: Comprehensive open reading frame/splice mutational analysis of syntrophin α was performed using PCR, DHPLC, and direct DNA sequencing on a cohort of 50 unrelated patients with LQT1–10 negative/phenotype positive LQTS (34 females; average age at diagnosis 26 ± 16 years; average QTc 531 ± 60.4 ms; QTc range 480 –759 ms). Mutations were engineered by site-directed mutagenesis and transiently expressed in HEK293 cells containing the stably-expressed SCN5A- encoded sodium channel α subunit (hNaV1.5). Results: Analysis of syntrophin α, encoded by SNTA1 , revealed 3 missense mutations in 2 patients (4%). A female diagnosed with LQTS at 13 years (QTc, 480 ms) with family history of autopsy-negative unexplained sudden death, was compound heterozygous for P74L/A257G while a male, diagnosed with LQTS at 18 years following syncopal episodes (QTc, 529 ms), hosted the A390V mutation. These mutations were absent in 600 reference alleles and A257G and A390V involved highly conserved residues. Functional studies revealed a marked leftward shift in sodium current activation for A257G and a significant rightward shift in channel inactivation for A390V-SNTA1. Both kinetic perturbations precipitated a ``gain-of-function” increase in the sodium channel window current. Conclusion: We provide the sentinel report of SNTA1 as a novel LQTS-susceptibility gene with a putative pathogenic mechanism involving a secondary ``gain-of-function” in the NaV1.5 sodium channel. Thus, CAV3-LQTS (LQT9), SCN4B-LQTS (LQT10), and now SNTA1-LQTS represent functional homologues with LQT3-like perturbations.
American Journal of Clinical Pathology, Indianapolis
Journal: JAMA (1965)

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
Hazards of phlebotomy in polycythemic patients with cardiovascular disease
Authors: III. Kiraly JF
Journal: JAMA (1976)

Three patients with polycythemia and previous evidence of cardiovascular disease underwent routine phlebotomies. Systolic hypotension followed by ineffective volume replacement with electrolyte solutions developed in all patients after phlebotomy. In two patients acute myocardial infarction and in a third cardiovascular collapse and death were temporally related to the procedure. This experience suggests that phlebotomy in patients with cardiovascular disease should be performed by the slow removal of small volumes of blood under continuous blood pressure monitoring. Effective restoration of the plasma volume with plasma or colloid is essential unless volume overload is present. (<i>JAMA</i>236:2080-2081, 1976)
Response of Cell Cultures to Asbestos Fibers
Authors: J. Bruch
Journal: Environmental Health Perspectives (1974)

The reaction of macrophages to asbestos and glass fibers was studied by light and by electron microscopy. Measurements were made of LDH release, staining with erythrosine B, and lactate production. Size and shape of asbestos fibers were found to have more effect than the physicochemical properties of the surface. Long fibers resulted in a protracted pathogenic but no acute cytotoxic effect.
Naval and Military Medical Services
Journal: BMJ (1888)

LJwue 23, 188& country districts, much more for travelling backwards and for- wardIs to a hiospital than efficient attendance at their own homes would cost.As for the risks, I need only instance a case where a child with chest affection travelled seven miles to a hospital in an open conveyance during inclement weather, and died in conse- (luence of the exposure; all this distance was traversed for the H:Lke of a few grains of a hypophosphite in powder.Under such circumstances as these I consider it nothing less then homicidal to encourage attendance, and the medical officers would best show their humanity by directing such poor persons to any efficient .eIf-suppDrtingdispensary in their own neighbourhood; it woutld bl< better.by the bye, if the amount of the subscriptions to these institutions were increased, and if no unqualified person were allowed to be in any way connected with them, unless it were stuch medical students as had progressed well with their studies and examinations.Then the scale of payment to poor-law medical officers is very ina(lequate; this is surely a fitting subject for some of the labour representatives in the Commons to take up.The annual drink bill is still far too large, and I think a small portion of the amount might be worthily diverted for the purpose of medical relief.-Iam, etc., W. L. THE TREATMENT OF AURAL EXOSTOSES.SIR,-In justice to Sir William Dalby, I feel it my duty to state
Abstract P234: Racial Disparities in Coronary Revascularization Procedure Mortality: Does the Type of Procedure Matter?
Authors: Alexander V Sergeev
Journal: Circulation (2013)

BACKGROUND: Racial disparities in treatment procedure mortality contribute to long-term mortality disparities. Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI; coronary angioplasty) are two common revascularization procedures for coronary heart disease (CHD) interventional therapy. In-hospital post-coronary revascularization procedure mortality contributes to long-term, overall CHD mortality. While racial disparities in long-term CHD mortality have been reported, existence of racial disparities in post-procedure mortality remains an open question of important implications. HYPOTHESIS: We hypothesized that racial disparities in post-CABG and post-PCI mortality would exist. METHODS: We conducted a study of in-hospital mortality in 427,864 patients [mean+SD age: 66.1+11.8 years; 68.5% (292,955 of 427,864) males] after CABG and PCI during the years 2007,2009. Patient race was classified as white, black, or other (Asian, Pacific Islander, Native American). Because post-procedure length of stay in the hospital is relatively short (days, not months), post-procedure in-hospital death was defined as a binary variable (discharged alive vs. deceased). Multivariable logistic regression models were used to obtain adjusted odds ratios (OR) for in-hospital death after CABG and PCI in relation to race, adjusting for confounding factors - patient and hospital characteristics (age, gender, socio-economic status, Elixhauser comorbidity measures, emergency department admission, rural/urban area status). RESULTS: Significantly higher percentage of black patients were admitted via emergency department (44.8%) as compared to other (37.8%) and white (36.2%) patients (p&lt;0.001). Compared to whites and other patients, blacks had higher prevalence of congestive heart failure, diabetes mellitus, hypertension, obesity, and renal failure (p&lt;0.001 for each condition). Crude post-CABG in-hospital mortality was 2.7% (2,982 of 111,830 patients) and post-PCI - 1.2% (3,890 of 316,034 patients). Adjusted post-CABG in-hospital mortality in blacks was higher than in whites (adjusted OR = 1.172, 95% CI: 1.006-1.364, p=0.042), but in other patients was similar to whites (adjusted OR = 1.048, 95% CI: 0.874-1.257, p=0.610). Adjusted post-PCI in-hospital mortality in blacks was lower (adjusted OR = 0.813, 95% CI: 0.710-0.931, p=0.003) and in other patients was higher (adjusted OR = 1.300, 95% CI: 1.129-1.496, p&lt;0.001) than in whites. CONCLUSIONS: Our findings are indicative of two distinctive patterns of racial disparities in post-coronary revascularization procedure mortality. Blacks have a higher post-CABG mortality and lower post-PCI mortality than whites. Other patients have a higher post-PCI mortality than whites, but similar post-CABG mortality. Further studies of the mechanisms responsible for these racial disparity patterns are needed.
Hyperprolactinemia and nonpuerperal mastitis (duct ectasia)
Authors: F. Peters
Journal: JAMA (1989)

In 108 patients with nonpuerperal mastitis (inflammatory symptoms of duct ectasia), serum prolactin levels were determined before, during, and after treatment. Twenty-nine patients (26.8%) exhibited transiently elevated prolactin levels during the period of inflammation (mean±SD level, 42 ±22 μg/L that returned to normal within 4 weeks. Twenty-two patients (20.4%) presented with more severe hyperprolactinemia (78 ±56 μg/L), and 15 were found to have pituitary microadenomas. In 11 cases, mastitis was the first symptom of hyperprolactinemia. A second group of 83 patients with known hyperprolactinemia and 83 normoprolactinemic controls were interviewed with regard to recent symptoms or past treatment of nonpuerperal mastitis. Sixteen hyperprolactinemic women (19.3%) and none of the controls reported that they had experienced mastitis. We conclude that duct ectasia is due in part to increased prolactin secretion. Thus, nonpuerperal mastitis may be a symptom of hyperprolactinemia. On the other hand, nonpuerperal mastitis may induce transient hyperprolactinemia (neurogenic hyperprolactinemia) of about 3 weeks' duration that is less pronounced than central hyperprolactinemia. (<i>JAMA</i>. 1989;261:1618-1620)