tbuckley/cabot-search huggingface dataset:
Neurochemical Aspects of Susceptibility to Depression
Authors: Pradeep J Nathan
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
Impact of Intermittent Screening and Treatment for Malaria among School Children in Kenya: A Cluster Randomised Trial
Authors: Katherine E. Halliday, George Okello, Elizabeth L. Turner, Kiambo Njagi, Carlos Mcharo, Juddy Kengo, Elizabeth Allen, Margaret M. Dubeck, Matthew C. H. Jukes, Simon J. Brooker
Journal: PLoS Medicine (2014)

Katherine Halliday and colleagues conducted a cluster randomized controlled trial in Kenyan school children in an area of low to moderate malaria transmission to investigate the effect of intermittent screening and treatment of malaria on health and education. Please see later in the article for the Editors' Summary
Long-term clinical and echocardiographic outcome of percutaneous mitral valvuloplasty
Authors: Duk-Hyun Kang, Seong-Wook Park, Jae-Kwan Song, Hyun-Sook Kim, Myeong-Ki Hong, Jae-Joong Kim, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2000)
Streptococcus pyogenes Preparation OK-432: Immunoprophylactic and Immunotherapeutic Effects on the Incidence of Spontaneous Leukemia in AKR Mice
Authors: Tadao Aoki, John P. Kvedar, Vincent W. Hollis, Grace S. Bushar
Journal: JNCI Journal of the National Cancer Institute (1976)

An inactivated and lyophilized preparation of a low virulence strain (Su) of Streptococcus pyogenes (group A) was designated OK-432. When 2- and 5-month-old AKR mice were inoculated im with OK-432 twice weekly throughout their life-spans, spontaneous leukemias occurred later and at a lower incidence than in control groups. By virus neutralization and cytotoxicity tests and by immunoelectron microscopy, antibodies against virus and cell-surface antigens of transplanted AKR leukemia were not detectable in sera of nonleukemic mice of any group. Whereas sera from mice treated with OK-432 were the only positive for interferon, viremia was clearly demonstrated in control groups by reverse transcriptase assays of the plasma.
People with special needs entitled to free education after 18, Irish court rules
Authors: Doug Payne
Journal: BMJ (2000)

The Irish High Court has ruled that the state must provide free primary education for severely mentally handicapped, autistic, and other people with special needs beyond the age of 18 and for as long as they may benefit from it.

The landmark decision has significant financial implications, and the judge noted that hundreds of similar claims are outstanding, with many more likely if the current situation persists.

The …
EEF1A2 inactivates p53 by way of PI3K/AKT/mTOR-dependent stabilization of MDM4 in hepatocellular carcinoma
Authors: Rossella Pellegrino, Diego F. Calvisi, Olaf Neumann, Venkatesh Kolluru, Josephine Wesely, Xin Chen, Chunmei Wang, Torsten Wuestefeld, Sara Ladu, Nahla Elgohary, Justo Lorenzo Bermejo, Bernhard Radlwimmer, Martin Zörnig, Lars Zender, Frank Dombrowski, Matthias Evert, Peter Schirmacher, Thomas Longerich
Journal: Hepatology (2013)

Mouse Double Minute homolog 4 (MDM4) gene up-regulation often occurs in human hepatocellular carcinoma (HCC), but the molecular mechanisms responsible for its induction remain poorly understood. Here we investigated the role of the phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin (PI3K/AKT/mTOR) axis in the regulation of MDM4 levels in HCC. The activity of MDM4 and the PI3K/AKT/mTOR pathway was modulated in human HCC cell lines by way of silencing and overexpression experiments. Expression of main pathway components was analyzed in an AKT mouse model and human HCCs. MDM4 inhibition resulted in growth restraint of HCC cell lines both in vitro and in vivo . Inhibition of the PI3K-AKT and/or mTOR pathways lowered MDM4 protein levels in HCC cells and reactivated p53-dependent transcription. Deubiquitination by ubiquitin-specific protease 2a and AKT-mediated phosphorylation protected MDM4 from proteasomal degradation and increased its protein stability. The eukaryotic elongation factor 1A2 (EEF1A2) was identified as an upstream inducer of PI3K supporting MDM4 stabilization. Also, we detected MDM4 protein up-regulation in an AKT mouse model and a strong correlation between the expression of EEF1A2, activated/phosphorylated AKT, and MDM4 in human HCC (each rho &gt; 0.8, P &lt; 0.001). Noticeably, a strong activation of this cascade was associated with shorter patient survival. Conclusion : The EEF1A2/PI3K/AKT/mTOR axis promotes the protumorigenic stabilization of the MDM4 protooncogene in human HCC by way of a posttranscriptional mechanism. The activation level of the EEF1A2/PI3K/AKT/mTOR/MDM4 axis significantly influences the survival probability of HCC patients in vivo and may thus represent a promising molecular target. (Hepatology 2014;59:1886–1899)
Abstract 1645: Discovery of AMG 232, an inhibitor of the MDM2-p53 interaction: From lead to a clinical candidate
Authors: Zhihong Li
Journal: Cancer Research (2014)

Abstract The p53 tumor suppressor is controlled by MDM2, which binds p53 and negatively regulates its transcriptional activity and stability. Many tumors overproduce MDM2 to impair p53 function. Therefore, restoration of p53 activity by inhibiting the p53-MDM2 binding represents an attractive novel approach to cancer therapy. We previously reported the discovery AM-8553, a potent and selective piperidinone inhibitor of the MDM2-p53 interaction (Rew et al. J. Med. Chem. 2012, 55, 4936). We report here continued research on the N-alkyl substituent of this series, focused in particular on a previously underutilized interaction in a shallow cleft on the MDM2 surface that led to the discovery of variety of sulfonamides and sulfones which gave rise to substantial improvements in biochemical and cellular potency. Further work led to discovery of AMG 232, which is currently being evaluated in human clinical trials for the treatment of cancer. AMG 232 is an extremely potent MDM2 inhibitor (SPR KD = 0.045 nM, SJSA-1 EdU IC50 = 9.1 nM), with remarkable pharmacokinetic properties. The compound interacts specifically with the p53-binding pocket of MDM2 and releases the p53 protein from negative control. Treatment of cancer cells expressing wild-type p53 with AMG 232, stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest and apoptosis. The compound showed excellent efficacy in a number of mouse tumor xenograft models and was well tolerated in preclinical toxicology studies at therapeutically relevant dosages. Citation Format: Zhihong Li. Discovery of AMG 232, an inhibitor of the MDM2-p53 interaction: From lead to a clinical candidate. [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 1645. doi:10.1158/1538-7445.AM2014-1645
Flavonoids-induced death in malignant cells through inhibition of IGF-1R
Authors: Ada Girnita, Leonard Girnita, Axelson Magnus, Olle Larsson
Journal: Cancer Research (2004)

4877  Background: Flavonoids are natural compounds found in fruits and vegetables, with a chemical structure related to Tamoxifen, an oestrogen and insulin like growth factor 1 receptor inhibitor. Insulin-like growth factor 1 receptor (IGF-1R) is a transmembrane tyrosine kinase receptor essential for protecting cells against apoptosis and chemotherapeutic treatments. Since is not an absolute requirement for normal cell growths it becomes clearly a perfect target for anti-tumour treatments. Aim: To compare the effect of some selected flavonoids, tamoxifen and etoposide on inducing apoptosis in different malignant cell lines over-expressing IGF-1R. Methods: We used some purified flavonoids (apigenin, genistein, podophyllotoxin and picropodophyllotoxin), tamoxifen and etoposide on different concentrations on melanoma (SK-Mel 5, SK-Mel 28, and DFB), Ewing sarcoma (ES1) and prostatic carcinoma (PC3) cell lines. We evaluated the degree of apoptosis by cell survival tests and annexin V / propidium iodide staining. The apoptotic effect was related with the effects of the compounds on IGF-1R inhibition. We used as negative controls untreated cells and R (-) cell line (IGF-1R negative). Results: The flavonoids and tamoxifen have induced apoptosis in the IGF-1R positive cells but not in the negative one. The amount of cellular death was different from one compound to another on the same cell line and it was changed from on cell line to another. The strongest effect on all cell lines was noticed after picropodophyllotoxin and podophyllotoxin treatment. They had the IC50 below 0.5 μM while for the others IC50 was over 20 μM. Conclusion: Our results suggest that some flavonoids could be useful tools in cancer treatment by targeting IGF-1R. Among them, picropodophyllotoxin and podophyllotoxin had the strongest effect on inhibition of IGF-1R phosphorylation.
An Inquiry into the Difficulties Encountered in the Reduction of Dislocations of the Hip.
Authors: Oscar Huntington Allis
Journal: JAMA (1896)

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
Postoperative starvation after gastrointestinal surgery
Authors: D B A Silk, N M. Gow
Journal: BMJ (2001)

Papers p 773 

The widespread practice of starving patients in the immediate period after gastrointestinal surgery has been challenged by a systematic review and meta-analysis in this issue (p 773), which finds that “nil by mouth” after gastrointestinal surgery may not be beneficial.1 Further, the apparently beneficial effects of early postoperative enteral feeding on infection rates and length of stay in hospital are compelling arguments in favour of a change in clinical practice.

The rationale of nil by mouth and gastric decompression is to prevent postoperative nausea and vomiting and protect the anastomosis, allowing it time to heal before being stressed by food. Nausea and vomiting, however, occur more commonly after upper gastrointestinal surgery than after resection of the small intestine and colon. In our clinical experience nasogastric decompression can usually be discontinued 12-24 hours after resection of the small intestine and colon.

There is no evidence that bowel rest and a period of starvation are beneficial for healing of wounds and anastomotic integrity. Indeed, the evidence is that luminal nutrition may enhance wound healing and increase anastomotic strength, …
Abstract P158: Excess CVD Risk Factors, CAC and Carotid IMT in US South Asians: Preliminary Results from the MASALA study
Authors: Alka M Kanaya, Michael Schembri, Swapna Dave, Ritu Gupta, Neerja Khurana, Shweta Srivastava, Matthew J Budoff, David Herrington, Kiang Liu, Namratha Kandula
Journal: Circulation (2012)

Background: South Asians (SA) have a disproportionate risk of heart disease and diabetes and are at greater risk for death from heart disease compared to other racial/ethnic groups. There are almost 3 million SA in the United States; SA are currently the second fastest growing U.S. ethnic group after Latinos. Objectives: To assess the prevalence of cardiovascular (CVD) risk factors and subclinical atherosclerosis in SA using similar methods and measures from the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study is a community-based cohort enrolling 900 SA between 40-79 years without known CVD at two clinical centers (University of California, San Francisco and Northwestern University, Chicago). At baseline, we are collecting demographic, cultural and lifestyle information, fasting blood tests, 2-hour glucose tolerance test, physical examination, carotid ultrasound for intima media thickness (IMT) and CT for coronary artery calcium (CAC). Results: To date, we have enrolled 368 participants in MASALA with a mean age of 56±9 years, of whom 98% are immigrants who have lived in the U.S. an average of 27±11 years. A majority are immigrants from India (85%), 6% from Pakistan, 1% each from Bangladesh, Sri Lanka and Nepal, and 6% from other diaspora countries. The table shows demographic, behavioral, and clinical characteristics of the cohort. The cohort has higher socioeconomic status, lower smoking and alcohol use, very low exercise, modest BMI, and higher prevalence of hypertension, diabetes, and subclinical atherosclerosis than reported in MESA ethnic groups. Conclusion: Despite having high socioeconomic attainment and modest BMI, SA have low physical activity levels and high prevalence of CVD risk factors and atherosclerosis. This population-based study of U.S. South Asians will provide further insights into the clinical, behavioral, and socio-cultural factors contributing to heart disease. MASALA participant characteristics, 2010-2011 Overall n=368 Men n=271 Women n=97 Education ≥Bachelor's degree, % 86 87 83 Family income ≥$100,000, % 60 62 55 Current smoking, % 5 6 1 Alcohol intake, &gt;1 drink/week 39 45 22 Exercise, median MET-min/week 960 982 885 BMI, kg/m2 26.6±4.9 26.5±4.9 26.8±5.0 Waist circumference, cm 95±10 97±10 91±11 LDL, mg/dl 108±32 108±31 109±32 HDL, mg/dl (median) 47 44 57 Triglycerides, mg/dl (median) 122 127 112 Hypertension, % 46 48 41 Diabetes, % 26 28 20 Common carotid IMT, mm 0.91±0.22 0.92±0.22 0.89±0.24 Internal carotid IMT, mm 1.24±0.44 1.24±0.45 1.22±0.42 CAC score, zero 1-100 &gt;100 50 31 19 44 35 21 69 20 11
The genetically isolated populations of Finland and Sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes
Authors: Iain A. Eaves, Tony R. Merriman, Rachael A. Barber, Sarah Nutland, Eva Tuomilehto-Wolf, Jaakko Tuomilehto, Francesco Cucca, John A. Todd
Journal: Nature Genetics (2000)
Life-Threatening Events During Endurance Sports
Authors: Lior Yankelson, Ben Sadeh, Liron Gershovitz, Julieta Werthein, Karin Heller, Pinchas Halpern, Amir Halkin, Arnon Adler, Arie Steinvil, Sami Viskin
Journal: Journal of the American College of Cardiology (2014)
Breast Cancer, Version 3.2013
Authors: Richard L Theriault, Robert W Carlson, Craig Allred, Benjamin O Anderson, Harold J Burstein, Stephen B Edge, William B Farrar, Andres Forero, Sharon Hermes Giordano, Lori J Goldstein, William J Gradishar, Daniel F Hayes, Clifford A Hudis, Steven J Isakoff, Britt-Marie E Ljung, David A Mankoff, P Kelly Marcom, Ingrid A Mayer, Beryl McCormick, Lori J Pierce, Elizabeth C Reed, Lee S Schwartzberg, Mary Lou Smith, Hatem Soliman, George Somlo, John H Ward, Antonio C Wolff, Richard Zellars, Dorothy A Shead, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2013)

These NCCN Guidelines Insights highlight the important updates specific to the management of HER2-positive metastatic breast cancer in the 2013 version of the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. These include new first-line and subsequent therapy options for patients with HER2-positive metastatic breast cancer.
Modifiable Behavioral Factors as Causes of Death—Reply
Authors: Ali H. Mokdad, James S. Marks, Donna F. Stroup
Journal: JAMA (2004)

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
Genetic Disorders of Renal Phosphate Transport
Authors: Elena Levtchenko, Joost Schoeber, Jacques Jaeken
Journal: New England Journal of Medicine (2010)

To the Editor: In their comprehensive review of genetic disorders of renal phosphate transport, Prié and Friedlander (June 24 issue) 1 claim that the role of NPT2a in renal phosphate handling has been shown by the association between heterozygous mutations in NPT2a and renal phosphate leak. 2 However, Virkki et al. 3 found no dominant negative effect of these NPT2a variants, which indicates that they are polymorphisms.Lapointe et al. 4 also identified NPT2a variants in patients with renal phosphate leak, but ruled out their functional significance by the finding of normal renal phosphate balance in family members carrying the same variants.The major contribution of NPT2a to renal phosphate balance was definitively established in a recent article in the Journal that reported autosomal recessive hypophosphatemic rickets with renal Fanconi's syndrome secondary to a loss-of-function mutation in SLC34A1 (also known as NPT2a), the gene that encodes NPT2a (also known as NaPi-IIa).
Abstract 11898: Effects of Insulin Glargine on Left Ventricular Mass and Function in Patients With Dysglycemia
Authors: Michelle Haroun, Darryl P Leong, Hisham Dokainish, Jackie Bosch, Rafael Diaz, Salim Yusuf, Herztel C Gerstein, Eva Lonn
Journal: Circulation (2014)

Introduction: Type 2 diabetes mellitus (T2DM) is associated with increased risk for left ventricular (LV) hypertrophy and heart failure (HF). Moreover, some drugs used to treat hyperglycaemia are associated with increased risk of HF. There are limited data on the effects of exogenous insulin on left ventricular mass (LVM) and function (LVF). Therefore, we evaluated the effects of insulin glargine on LVM and LVF in the echocardiographic substudy of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784). Methods: Patients aged ≥ 50 years with dysglycemia (early T2DM, impaired glucose tolerance, or impaired fasting glucose) and with cardiovascular (CV) disease or CV risk factors were randomized to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard glycemic care. Echocardiograms were performed at baseline and after 3 years. Changes in LVM, LV ejection fraction (LVEF), wall motion score (WMS), LV end-diastolic and end-systolic volume (LVEDV and LVESV), E/A, and E/E’ were compared between the study groups using mixed effects modelling. Results: 564 patients aged 64 ± 8 years were evaluated; 30% were women, 84% had a history of hypertension and 32% of prior myocardial infarction. This is the largest reported study on the effects of exogenous insulin on LVM and LVF. There were no significant differences in the changes over time in LVM and LV systolic and diastolic function between the study groups (Table). Conclusions: In people with CV disease and/or CV risk factors and dysglycemia three years of treatment with insulin glargine has a neutral effect on LVM and on LV systolic and diastolic function. These findings support the CV safety of insulin glargine.