tbuckley/cabot-search huggingface dataset:
Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis
Authors: Annalisa Frattini, Paul J. Orchard, Cristina Sobacchi, Silvia Giliani, Mario Abinun, Jan P. Mattsson, David J. Keeling, Ann-Katrin Andersson, Pia Wallbrandt, Luigi Zecca, Luigi D. Notarangelo, Paolo Vezzoni, Anna Villa
Journal: Nature Genetics (2000)
p53 status is more likely than basal subtype to predict survival in African-American women with breast cancer
Authors: Keith A. Dookeran, X. Gao, Y. Wang, K. Ferrer, M. Sekosan, B. Lukaszczyk, G. Roman, R. De La Torre, A. Jacobson, E. K. Radeke, T. Mackevicius, H. A. Zaren, W. McCaskill-Stevens
Journal: Clinical Cancer Research (2006)

A63   Background. Outcome disparities for African-American (AA) women with breast cancer may in part be due to biologically aggressive tumors, including more frequent p53 and basal (i.e. negative status for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2) tumor subtypes. We hypothesized that survival would be worse for AA women with either p53 or basal subtypes. Methods. Tumors from 182 consecutive underserved AAs were evaluated for p53 and basal subtypes with immunohistochemistry, on paraffin embedded tissue. Univariate analyses were performed with the use of a two-sided log-rank test and multivariate analysis with the Cox proportional-hazards model. Survival was computed by the Kaplan-Meier method and correlated with tumor subtype. Results. A total of 55 (30.2%) and 62 cases (34.1%) were found to have p53 and basal subtypes. Young age (p=0.032; odds ratio [OR]=0.97, 95% Confidence Interval [CI]=0.943-0.997), high AJCC stage (p=0.0001; OR=3.38, 95% CI=1.768-6.454), high tumor grade (p=0.0001; OR=17.05, 95% CI=6.768-42.82) and positive p53 status (p=0.005; OR=2.54, 95%CI=1.315-4.887), were all significantly correlated with basal subtype. Adjustment for age and stage did not alter correlation of grade (p=0.0001; OR=14.05, 95%CI=5.69-37.05) and p53 status (p=0.007; OR=2.578, 95%CI=1.291-5.148) with basal subtype. At median follow-up of 40 months, univariate analyses showed that both p53 (p=0.033; Hazard Ratio [HR]=1.829, 95% CI=1.049-3.189) and basal (p=0.017; HR=1.9, 95% CI=1.126-3.27) subtypes were significantly correlated with worse survival. However after adjustment for age & stage, only p53 status (p=0.047; HR=1.755, 95% CI=1.007-3.061) remained significantly correlated with worse survival. Conclusions. Although as expected, p53 status was significantly correlated with basal subtype, only abnormal p53 expression was significantly correlated with poorer survival in multivariate analysis. These results suggest that p53 status is more likely than basal subtype to predict survival in AA women with breast cancer.
Abstract P019: Identifying Laboratory Markers of Incident Myocardial Infarction through Electronic Health Records
Authors: Benjamin A Goldstein, Tara I Chang, Trevor Hastie, Wolfgang C Winkelmayer
Journal: Circulation (2014)

Background: Patients on hemodialysis (HD) are at high risk of cardiac events including myocardial infarction (MI). Electronic health records (EHRs) present a unique opportunity to observe biomedical changes in patients over time. Purpose: To assess whether there were any distinct changes in laboratory values prior to an incident MI. Methods: Using EHR data from a large dialysis organization, we identified 6,468 patients with an incident MI and selected an equal number of patients receiving dialysis on the same date without an MI. We abstracted six months of 12 regularly collected laboratory measures for their potential utility as a marker for incident MI: albumin, calcium, co2, creatinine, ferritin, hemoglobin, iron saturation, phosphorus, platelet, potassium, single pool Kt/V and white blood cell count. We used natural cubic spline regression to determine whether the trajectory of the laboratory values differed amongst patients with and without an incident MI. Results: Of the 12 laboratory measures, 7 showed a distinct change between patients with and without MI, 14 to 28 days before the incident event. Three measures were related to inflammation (white blood cell count, iron saturation, and ferritin; see Figure 1), 3 measures were related to malnutrition (albumin, creatinine, phosphorous), along with single pool kt/v. Conclusion: Distinct changes in routinely collected laboratories are observed prior to an MI. Future studies based on our results will focus on whether these changes can be used in real-time to predict MI risk in HD patients.
Reduced Intensity Transplant May Improve Survival in Patients Over the Age of 40, Especially If a Sibling Donor Is Used: Pooled Analysis of 2454 Patients and 407 Transplants in the UK NCRI AML15 and AML16 Trials
Authors: Nigel H Russell, Robert K. Hills, Lars Kjeldsen, John L Yin, Charles Craddock, Alan K Burnett
Journal: Blood (2012)
Abstract 5603: Aryl hydrocarbon receptor, a receptor for environmental pollutants, promotes tumorigenesis via intestine-specific homeobox expression in hepatocellular carcinoma
Authors: Li-Ting Wang, Shen-Nien Wang, Shih-Hsien Hsu
Journal: Cancer Research (2014)

Abstract Environmental pollutants often cause diseases. Aryl hydrocarbon receptor (AHR), a major transcriptional factor in the xenobiotic response, regulates cellular signaling and metabolism, thereby influencing disease progression. The detailed regulatory mechanisms, however, remain unclear. Here we demonstrate that AHR expression promotes tumorigenesis and is associated with shorter survival time in HCC patients. These phenomena appear to be mediated by activation of a target proto-oncogene, intestine-specific homeobox (ISX), in vitro and in vivo. The strong correlation of expression and cellular transcriptional regulation between AHR and ISX (in tumor and hepatoma cells) underscore the significant role of this duo in HCC tumorigenesis and prognosis. Our experiments with the ablation of ISX expression in AHR-mutant mice and hepatoma cells further support the essential roles of AHR and ISX in liver and tumor development. These results advance the understanding of the cellular function of AHR and of its downstream gene, ISX, in HCC progression. Our data may help to develop a new therapeutic approach to HCC. Citation Format: Li-Ting Wang, Shen-Nien Wang, Shih-Hsien Hsu. Aryl hydrocarbon receptor, a receptor for environmental pollutants, promotes tumorigenesis via intestine-specific homeobox expression in hepatocellular carcinoma. [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 5603. doi:10.1158/1538-7445.AM2014-5603
International Symposium on Hepatotoxicity
Authors: Joseph R. Bloomer
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article International Symposium on Hepatotoxicity Get access JNCI: Journal of the National Cancer Institute, Volume 48, Issue 3, March 1972, Page 845, https://doi.org/10.1093/jnci/48.3.845-a Published: 01 March 1972
An unusual occurrence: "I can't turn my car to the left"
Authors: M. Oliver
Journal: BMJ (1998)

“When I turn the car sharply to the left I feel a sort of grating in my back. The problem is that there is an acute turn to the left from my rough little road into the main road.” This intelligent, 54 year old woman had no other complaints or comments, except that “it occurs so often now that I have decided to turn to the right out of my road and go in the opposite direction for a few hundred yards, then reverse into a drive way and turn back in the direction I wanted to go. It is not painful and the grating stops as soon as I straighten up the car. …
Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism
Authors: Kristiina Avela, Marita Lipsanen-Nyman, Niina Idänheimo, Eva Seemanová, Sally Rosengren, Tomi P. Mäkelä, Jaakko Perheentupa, Albert de la Chapelle, Anna-Elina Lehesjoki
Journal: Nature Genetics (2000)
Abstract 3878: The Validity of the Charlson Comorbidity Index in Predicting Survival Following Permanent Pacemaker Implantation: A Population-Based Cohort Study
Authors: Daniel Z Uslan, Imad M Tleyjeh, Larry M Baddour, Paul A Friedman, Sarah M Stoner, Jennifer L St. Sauver, David L Hayes
Journal: Circulation (2006)

Objective: To examine the validity of the Charlson comorbidity index (CCI) in predicting long-term survival after permanent pacemaker (PPM) implantation in a population-based cohort. Methods: Using...
Failures in genetic programming may cause death and defects in cloned animals
Authors: Scott Gottlieb
Journal: BMJ (2001)

Defects in a process called gene imprinting may explain why cloned animal embryos often fail to survive or give rise to animals with significant birth defects, a new report has said.

Despite recent success in the cloning of various animals, the use of adult somatic cells as the source of donor nuclei has faced obstacles, among them high rates of abortion, high birth weight among cloned offspring, and an increased likelihood of perinatal death. These shortcomings may be the result of incomplete genetic reprogramming of the donor DNA, …
TIA Time Bombs Remain Undertreated
Authors: Mike Mitka
Journal: JAMA (2005)

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
NPT1/SLC17A1 Is a Renal Urate Exporter in Humans and Its Common Gain‐of‐Function Variant Decreases the Risk of Renal Underexcretion Gout
Authors: Toshinori Chiba, Hirotaka Matsuo, Yusuke Kawamura, Shushi Nagamori, Takashi Nishiyama, Ling Wei, Akiyoshi Nakayama, Takahiro Nakamura, Masayuki Sakiyama, Tappei Takada, Yutaka Taketani, Shino Suma, Mariko Naito, Takashi Oda, Hiroo Kumagai, Yoshinori Moriyama, Kimiyoshi Ichida, Toru Shimizu, Yoshikatsu Kanai, Nariyoshi Shinomiya
Journal: Arthritis & Rheumatology (2014)

Objective Serum uric acid (SUA) levels in humans are mainly regulated by urate transporters. Recent genome‐wide association studies suggested that common variants of the human sodium‐dependent phosphate cotransporter type 1 gene ( NPT1/SLC17A1 ) influence SUA. NPT1 has been reported to mediate urate transport, but its physiologic role in regulating SUA in humans remains unclear. Furthermore, the findings of replication studies of the relationship between NPT1 variants and gout have been inconsistent. The aims of this study were to investigate the effect of NPT1 on gout and to determine its physiologic role. Methods Five hundred forty‐five male Japanese patients with gout and 1,115 male Japanese control subjects were genotyped for rs1165196 (I269T), a common missense variant in NPT1 . Analyses of the association between rs1165196 and gout were then conducted, focusing especially on renal underexcretion (RUE) gout. Immunohistochemical analysis and functional analysis using Xenopus oocytes were also performed. Results Single‐nucleotide polymorphism rs1165196 significantly decreased the risk of RUE gout (odds ratio 0.73, P = 0.031) but did not confer a risk for all gout ( P = 0.123). The immunohistochemical analysis revealed that human NPT1 is localized to the apical membrane of the renal proximal tubule. The functional analysis using Xenopus oocyte expression systems showed that rs1165196 increases NPT1‐mediated urate export. Conclusion This study showed that NPT1 is a urate exporter located in the renal proximal tubule in humans, and that its common gain‐of‐function variant, rs1165196, causes RUE gout, a major subtype of gout. These findings enable us to deepen our understanding of the physiologic role of NPT1 as a renal urate exporter as well as its pathophysiologic role in gout.
Endpiece: Our own way
Authors: L. Tsu
Journal: BMJ (1999)

However, in two cases clinically important antibiotics have been used: a maize developed by Novartis contained a gene for ampicillin resistance, and a potato developed by Avebe contained a gene for amikacin resistance.A further complication with the maize is that the material was intended to be used unprocessed in animal feed and that the antibiotic resistance gene was under the control of a bacterial promoter.This led to concerns that the antibiotic resistance gene might be transferred to animal gut flora (including human pathogens), which might then acquire resistance to a clinically useful antibiotic.As a consequence, both these genetically modified crops are having difficulties gaining full regulatory approval. 17 The Advisory Committee on Novel Foods and Processes has called for the development of different marker systems, 16 and there are signs that alternative technologies are being developed. 1 In the meantime it is imperative that the clinical use of antibiotics is not compromised.
Right Bundle-Branch Block, ST-Segment Elevation, and Sudden Death
Authors: Bortolo Martini, Andrea Nava, Domenico Corrado, Gaetano Thiene
Journal: Circulation (2000)

The review article of Alings and Wilde 1 on the syndrome of right bundle-branch block ST-segment elevation and sudden death, ignores many of the published data on this disease.It is not true that most of the published cases affected by the disease show no heart abnormalities. 2 Since the first detailed description of the syndrome in 1988 -1989 by our group, 3,4 a number of patients with similar ECG patterns (including some in the Brugada series) have been recognized as having structural heart disease, particularly of the conduction system and/or right ventricle, by both invasive and noninvasive techniques.Right ventricular abnormalities (at angiography, 2D echo, or MRI), a positive late potential study, a prolonged HV interval (indicative of an organic conduction disturbance), an abnormal right ventricular biopsy, and fibro-fatty replacement of the right ventricle have all been documented. 1,5From our data, it is evident that the right bundle-branch block pattern and ST-segment elevation (according to electrophysiological and necropsy data) are related to a diseased conduction sytem both at the septal and intramyocardial levels. 5The ST-segment elevation in the right precordial leads, especially when associated with minor forms of right bundlebranch block, 3 has been explained in some cases by involvement of genetically isolated defective ion channels, which results in voltage gradient of repolarization between an abnormal epicardial action potential and a normal endocardial one. 1 This transmural dispersion of repolarization may either be acquired or enhanced in the setting of ischemia, inflammation, and degenerative heart disease.In this regard, myocyte degeneration and necrosis in right ventricular cardiomyopathy characteristically progresses from the epicardium, which is always involved, to the endocardium, which can be spared from the disease.A definitive diagnosis of functional electrical disease, underlying a "distinct syndrome," cannot be advanced before a detailed clinical and morphological investigation, including necropsy in fatal cases, rules out a concealed heart muscle disease.
Abstract 14026: Atrial Fibrillation is Associated with Altered Left Atrial 3D Hemodynamics and Increased Stasis
Authors: Daniel C Lee, Michael Markl, Jason Ng, Maria Carr, Brandon C Benefield, James C Carr, Jeffrey J Goldberger
Journal: Circulation (2014)

Introduction: Clinical scores used for stroke risk estimation in atrial fibrillation (AF) have limited predictive accuracy. 4D Flow MRI can acquire blood flow in a volume data set encompassing the entire left atrium (LA) with quantification of blood velocity in 3 orthogonal directions for every voxel at multiple time points throughout the cardiac cycle (4D = 3D coverage + time). Hypothesis: 4D Flow MRI can assess 3D LA flow abnormalities in AF patients, which may potentially be linked to stroke. Methods: We performed 4D flow MRI in 30 volunteers (10 young, 20 older) and 70 patients with a history of AF: 40 in sinus rhythm (AF-sinus) and 30 in AF during MRI scan (AF-afib). The typical LA contained 3000 voxels and 18 phases per voxel. LA flow velocity histograms for each patient were quantified by mean LA velocity, median LA velocity, and the percentage of LA velocities &lt; 0.2 m/s (%stasis). CHA2DS2-VASc scores were calculated for each patient. Results: Mean LA velocity, median LA velocity, and %stasis were significantly different between groups: young volunteers (0.26±0.02 m/s, 0.23±0.02 m/s, 37.3±7.6%), older volunteers (0.21±0.03 m/s, 0.20±0.03 m/s, 52.2±16.0%), AF-sinus (0.18±0.03 m/s, 0.17±0.03 m/s, 67.5±16.9%), and AF-afib (0.16±0.01 m/s, 0.14±0.03 m/s, 78.2±12.9%), p &lt; 0.0125 for all comparisons. CHA2DS2-VASc had moderate but significant correlations with mean LA velocity (R 2 =0.27, p&lt;0.001), median LA velocity (R 2 =0.23, p&lt;0.001), and stasis% (R 2 =0.26, p&lt;0.001). LA flow indices also correlated significantly with age, LA volume, and left ventricular ejection fraction (LVEF) as seen in the Table. Conclusions: Left atrial 4D flow MRI is a novel approach to identify patients with reduced LA blood velocities and increased LA stasis. Further study is needed to determine whether these measures can improve upon the CHA2DS2-VASc score for stroke risk prediction and enhance individual decisions on anticoagulation in patients with AF.
Abstract 2561: Yeast vector-encoding multiple MUC1 agonist epitopes (yeast-MUC1) can induce MUC1-specific T-cell immune responses
Authors: Kwong Y. Tsang, Benjamin Boyerinas, Caroline Jochems, Tim Rodell, Thomas King, Jeffey Schlom
Journal: Cancer Research (2014)

Abstract The tumor-associated antigen MUC1 is overexpressed on various human hematological and epithelial malignancies. The MUC1 molecule, which has an N-terminal (MUC1-N) and a C-terminal (MUC1-C, which has been shown to act as an oncogene), is an attractive target for cancer immunotherapy. We have identified and reported 10 agonist epitopes (7 in the C-terminus, 2 in the N-terminus VNTR region, and 1 in the non-VNTR region) that enhance production of CD8 cytotoxic T lymphocytes. These epitopes span HLA-A2, HLA-A3, and HLA-A24 MHC class I alleles, thus encompassing the majority of the North American population. Compared to native epitopes, these agonist epitopes more efficiently generate MUC1-specific T cells, induce production of IFN-gamma by MUC1-specific T cells, and lyse human tumor cells expressing MUC1 native epitopes in an MHC-restricted manner. We have previously shown that heat-killed recombinant Saccharomyces cerevisiae yeast genetically modified to express carcinoembryonic antigen can efficiently activate human dendritic cells (DCs) and stimulate CEA-specific CD8+ T cells. Here, we investigated the ability of a Saccharomyces cerevisiae vector containing the MUC1 transgene (yeast-MUC1) and encoding MUC1 with 8 agonist epitopes to activate human DCs, stimulate MUC1-N- and MUC1-C-specific T cells, and generate MUC1-specific T cells. We show here for the first time that human DCs treated with yeast-MUC1 vectors can activate MUC1-N and MUC1-C agonist-specific T-cell lines and can act as antigen-presenting cells to generate MUC1-N- and MUC1-C-specific T cells specific to each agonist epitopes, and that these T cells are capable of lysing MUC1-expressing tumor cells. Together, these findings provide a rationale for further clinical evaluation of yeast-MUC1 constructs encoding MUC1 agonist epitopes in cancer vaccine immunotherapy. Citation Format: Kwong Y. Tsang, Benjamin Boyerinas, Caroline Jochems, Tim Rodell, Thomas King, Jeffey Schlom. Yeast vector-encoding multiple MUC1 agonist epitopes (yeast-MUC1) can induce MUC1-specific T-cell immune responses. [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 2561. doi:10.1158/1538-7445.AM2014-2561
Counting the dead in China
Authors: A. D Lopez
Journal: BMJ (1998)

Papers pp 1411, 1423

Purely descriptive statistics on the numbers of people dying from different causes at various ages can be of enormous importance. But it is not enough merely to count “who dies of what disease”: the causes of those diseases, particularly in large populations, need also to be reliably measured and their evolution monitored. In rich countries the established vital registration systems, in some cases dating back over 100 years,1 can be used to assess disease patterns and trends, while decades of epidemiological research have identified some of the principal causes of such trends, particularly tobacco use. 2 3 In poorer countries, however, vital registration systems are not yet sufficiently well developed to document disease trends and cannot support large scale studies of the avoidable causes of disease.4

To assess the main patterns of mortality and the main avoidable causes of premature death in large developing …
Radiation doses in computed tomography
Authors: Madan M Rehani, Manorma Berry
Journal: BMJ (2000)

Computed tomography has made dramatic advances, both in its breadth of application and in its technological improvements. The advances are such that it is possible with the spiral technique to carry out an entire examination of the chest within a single breathhold as against a few minutes in earlier systems. Yet these advances have brought with them the potential for greatly increased doses of radiation to the patient.

Until a few years ago computed tomography constituted about 2-3% of all radiological examinations but contributed about 20-30% of the total radiation load from medical use of ionising radiation.1 2 A recent report from the Royal College of Radiologists in the United Kingdom states, “CT now probably contributes almost half of the collective dose from all x ray examinations.”3 Although magnetic resonance imaging was expected to reduce the frequency of computed tomography, this has not happened. Indeed, the use of computed tomography has grown. It is now often used as an adjunct to radiotherapy or chemotherapy; interventional procedures use computed tomography …