tbuckley/cabot-search huggingface dataset:
Abstract 5241: Accurate quantitation of micro RNA by chip-based digital PCR
Authors: Yalei Wu, Victoria Dahlhoff, Lin He, Caifu Chen
Journal: Cancer Research (2014)

Abstract MicroRNAs (miRNAs) are small non-coding RNAs that function to regulate gene expression at transcriptional and post-transcriptional level. Mature miRNAs are short, usually 18-23 nucleotides (nt) in length, with high homology in the seed region (position 2-8 from the 5′ end of a mature miRNA) within each family. This presents a great challenge when designing assays for quantitation by real-time polymerase chain reaction (PCR). Existing miRNA assays often trade in sensitivity and/or assay performance for specificity. Comparison between two different mature miRNAs with quantitative real-time PCR (qPCR) requires generating standard curves and characterizing PCR efficiency and sensitivity. Here we report a chip-based digital PCR technology. With this technology, we are able to accurately quantitate mature miRNAs without characterizing and optimizing the assay. Briefly, we input the same amount (ratio=1:1) of synthetic hsa-miR-19b and hsa-miR-92a. We then quantitated the miRNAs using reverse transcription followed by quantitative RT-PCR or chip-based QuantStudio™ 3D digital PCR (dPCR). Data from qPCR showed a delta Ct=2.58 between the cDNAs. This converted to a 3.84 fold difference between the two mature miRNAs, which deviated 284% from the input ratio, which equals 1. However, the data from dPCR indicated that the ratio between the amounts of the two mature miRNAs was 0.94 ± 0.02 (SD). Although statistically different, the results from dPCR deviated only 5% from the input ratio. Compared to qPCR, dPCR significantly enhanced the precision in sample quantitation. In summary, our study demonstrated that the chip-based dPCR technology has greatly increased precision in quantitating miRNA samples. The simplified workflow and improved output of dPCR are very useful features in broad applications such as revealing small changes in the miRNA expression levels. Citation Format: Yalei Wu, Victoria Dahlhoff, Lin He, Caifu Chen. Accurate quantitation of micro RNA by chip-based digital PCR. [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 5241. doi:10.1158/1538-7445.AM2014-5241
Privately run trust is first in England to be rated "inadequate" on patient care
Authors: G. Iacobucci
Journal: BMJ (2015)

England’s first privately run NHS hospital has been placed into special measures by the Care Quality Commission after it uncovered serious failings at the trust. Hinchingbrooke Health Care NHS Trust in Cambridgeshire received an overall rating of “inadequate” after an inspection, which raised particular concerns about its emergency and medical care services.1

The hospital, which was franchised when the private firm Circle took over its management in 2012, was rated as “inadequate” with regard to whether its services were safe, well led, and caring and as “requiring improvement” on the effectiveness and responsiveness of its services.

This was the first …
Complement-dependent Proinflammatory Properties of the Alzheimer's Disease β-Peptide
Authors: Bonnie M. Bradt, William P. Kolb, Neil R. Cooper
Journal: The Journal of Experimental Medicine (1998)

Large numbers of neuritic plaques (NP), largely composed of a fibrillar insoluble form of the β-amyloid peptide (Aβ), are found in the hippocampus and neocortex of Alzheimer's disease (AD) patients in association with damaged neuronal processes, increased numbers of activated astrocytes and microglia, and several proteins including the components of the proinflammatory complement system. These studies address the hypothesis that the activated complement system mediates the cellular changes that surround fibrillar Aβ deposits in NP. We report that Aβ peptides directly and independently activate the alternative complement pathway as well as the classical complement pathway; trigger the formation of covalent, ester-linked complexes of Aβ with activation products of the third complement component (C3); generate the cytokine-like C5a complement-activation fragment; and mediate formation of the proinflammatory C5b-9 membrane attack complex, in functionally active form able to insert into and permeabilize the membrane of neuronal precursor cells. These findings provide inflammation-based mechanisms to account for the presence of complement components in NP in association with damaged neurons and increased numbers of activated glial cells, and they have potential implications for the therapy of AD.
Haploid Inactivation of the Amplified-in-Breast Cancer 3 Coactivator Reduces the Inhibitory Effect of Peroxisome Proliferator-Activated Receptor γ and Retinoid X Receptor on Cell Proliferation and Accelerates Polyoma Middle-T Antigen-Induced Mammary Tumorigenesis in Mice
Authors: Hao Zhang, Shao-Qing Kuang, Lan Liao, Suoling Zhou, Jianming Xu
Journal: Cancer Research (2004)

Abstract The amplified-in-breast cancer 3 (AIB3) is a nuclear receptor coactivator amplified and overexpressed in human breast cancers. AIB3−/− mice die during gestation, whereas AIB3+/− mice exhibit normal development. Here, we demonstrate that AIB3 protein is mainly located in the nuclei of mammary epithelial cells and tumor cells and its levels are elevated in mammary epithelial cells at middle pregnant stage and in mammary tumor cells. To examine whether AIB3 reduction affects mammary tumorigenesis, we generated wild-type mouse mammary tumor virus/polyoma middle-T (WT/PyMT) and AIB3+/−/PyMT mice. Mammary tumor development in AIB3+/−/PyMT female and male mice was substantially accelerated compared with that in WT/PyMT mice, because of increased cell proliferation in early tumorigenic lesions, including ductal hyperplasia and mammary intraepithelial neoplasia. Tumor formation in nude mice that received premalignant AIB3+/−/PyMT mammary tissue was much faster than in nude mice that received transplants of premalignant WT/PyMT mammary tissue, which indicated that the accelerated tumorigenesis in AIB3+/−/PyMT mammary glands is due to a mammary epithelial autonomous defect. Expression of PyMT, estrogen receptor α and estrogen receptor α-regulated genes was unaffected in AIB3+/−/PyMT mammary glands, which suggests that the acceleration of mammary tumor formation in AIB3+/−/PyMT mice was not a consequence of changes in PyMT expression or in estrogen receptor function. Importantly, the inhibitory effects of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid-X receptor (RXR) ligands on AIB3+/−/PyMT cell proliferation and the transcriptional function of PPARγ in AIB3+/−/PyMT cells were reduced. Thus, AIB3 haplodeficiency may facilitate PyMT-induced tumorigenesis through a partial impairment of PPARγ and RXR function. These results suggest that AIB3 may be a tumor suppressor that is required for the inhibition of cell proliferation by PPARγ and RXR.
Increased urinary excretion of thromboxane B2 and 2,3-dinor-TxB2 in cyclosporin A nephrotoxicity
Authors: Ariela Benigni, Chiara Chiabrando, Antonella Piccinelli, Norberto Perico, Marco Gavinelli, Lucinda Furci, Osvaldo Patino, Mauro Abbate, Tullio Bertani, Giuseppe Remuzzi
Journal: Kidney International (1988)
The Medical Injunction of Stimulants
Authors: A. C. Rabagliati
Journal: BMJ (1877)

Germline mutations in the BRCA1 tumour suppressor gene on chromosome 17q21 are responsible for approximately half of the cases of hereditary breast cancer, including the majority of familial breast/ovarian cancers. To increase our knowledge of the spectrum of BRCA1 mutations, we have extended our analysis to include patients with varied family histories of cancer of the breast, ovary, and at multiple other sites. We have analysed 23 unrelated familial cases using direct sequencing or a combination of dideoxy fingerprinting and sequencing procedures. Twenty one of these families contained three or more cases of breast or ovarian cancer and two families had one case of breast cancer diagnosed before the age of 40 and one case of ovarian cancer. The common frameshift mutation 5382insC was detected in two patients, and the 185delAG mutation was found in a family of Ashkenazi Jewish descent. The novel frameshift mutation 3450del4 (CAAG) was detected in a patient who developed breast cancer at the age of 28 and ovarian cancer at the age of 34. Three other women in this family were diagnosed with breast cancer at the ages of 26, 29, and 40. The novel framshift mutation 2953del3+C was found in a French Canadian woman who had developed two primary cancers of the breast at the age of 37 and 38 and renal cancer at the age of 38.
FDA proposes higher fees for drug approvals to cover postmarketing surveillance
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

<h3>Abstract</h3> The genesis of broad neuronal classes from multipotential neural progenitor cells has been extensively studied, but less is known about the diversification of a single neuronal class into multiple types. We used single-cell RNA-seq to study how newly-born (postmitotic) mouse retinal ganglion cell (RGC) precursors diversify into ~45 discrete types. Computational analysis provides evidence that RGC type identity is not specified at mitotic exit, but acquired by gradual, asynchronous fate restriction of postmitotic multipotential precursors. Some types are not identifiable until a week after they are generated. Immature RGCs may be specified to project ipsilaterally or contralaterally to the rest of the brain before their type identity has been determined. Optimal transport inference identifies groups of RGC precursors with largely non-overlapping fates, distinguished by selectively expressed transcription factors that could act as fate determinants. Our study provides a framework for investigating the molecular diversification of discrete types within a neuronal class.
Endovascular Aneurysm Repair — Is It Durable?
Authors: K. Craig Kent
Journal: New England Journal of Medicine (2010)

Abdominal aortic aneurysm is a lethal condition associated with an 85% risk of death after rupture. Optimal treatment relies on early detection followed by prophylactic surgical intervention. Although aneurysms are traditionally treated with open surgery, the use of endovascular repair has increased dramatically and is the most frequent form of therapy in the United States.1 As is often the case with new surgical techniques, there may be trade-offs, including reduced invasiveness, durability, and cost. To weigh these trade-offs, two randomized trials comparing endovascular repair with open surgery have been conducted, the United Kingdom Endovascular Aneurysm Repair 1 (EVAR-1) trial2 and . . .
TCR affinity and specificity requirements for human regulatory T-cell function
Authors: Gabriela Plesa, Lingjie Zheng, Andrew Medvec, Caleph B. Wilson, Camila Robles-Oteiza, Nathaniel Liddy, Alan D. Bennett, Jessie Gavarret, Annelise Vuidepot, Yangbing Zhao, Bruce R. Blazar, Bent K. Jakobsen, James L. Riley
Journal: Blood (2012)
Thyroxine or Iodine Therapy for Thyroid Nodules
Authors: Joseph Di Poala Sr.
Journal: Annals of Internal Medicine (1995)

Letters1 August 1995Thyroxine or Iodine Therapy for Thyroid NodulesJoseph Di Poala Sr.Joseph Di Poala Sr.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-3-199508010-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the article by La Rosa and colleagues [1], which described the treatment of benign solitary solid cold nodules of the thyroid. I question the authors' rationale for treatment. Presuming that these nodules are completely asymptomatic and truly benign, this management strategy is preventive rather than therapeutic. According to the U.S. Preventive Task Force recommendations, performance of a preventive service is based on the quality of evidence that this service results in more good than harm [2].After the thyroid nodule is determined to be benign by fine-needle aspiration—which has been proved to be ...References1. La Rosa GL, Lupo L, Giuffrida D, Gullo D, Vigneri R, Belfiore A. Levothyroxine and potassium iodide are both effective in treating benign solitary cold nodules of the thyroid. Ann Intern Med. 1995; 122:1-8. Google Scholar2. Guide to Clinical Preventive Services: An Assessment of the Effectiveness of 169 Interventions. Report of the U.S. Preventive Services Task Force. Baltimore: Williams & Wilkins; 1989. Google Scholar3. Gharib H, Goellner R. Fine needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med. 1993; 118:282-9. Google Scholar4. Kuma K, Matsuzuka F, Kobayaski A, Hirai K, Morita S, Miyauchi A, et al. Outcome of long standing solitary thyroid nodules. World J Surg. 16:583-7. Google Scholar5. Gharib H. Fine needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect. Mayo Clin Proc. 1994; 69:44-9. Google Scholar Author, Article, and Disclosure InformationAuthors: Joseph Di Poala Sr. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1995Volume 123, Issue 3Page: 235-236KeywordsCardiovascular therapyForecastingOsteoporosisResearch laboratoriesThyroidThyroxine ePublished: 15 August 2000 Issue Published: 1 August 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Isolated Low Levels of High-Density Lipoprotein Cholesterol Are Associated With an Increased Risk of Coronary Heart Disease
Authors: Rachel R. Huxley, Federica Barzi, Tai Hing Lam, Sebastien Czernichow, Xianghua Fang, Tim Welborn, Jonathan Shaw, Hirotsugu Ueshima, Paul Zimmet, Sun Ha Jee, Jeetesh V. Patel, Ian Caterson, Vlado Perkovic, Mark Woodward
Journal: Circulation (2011)

Previous studies have suggested that there is a novel dyslipidemic profile consisting of isolated low high-density lipoprotein cholesterol (HDL-C) level that is associated with increased risk of coronary heart disease, and that this trait may be especially prevalent in Asian populations.Individual participant data from 220 060 participants (87% Asian) in 37 studies from the Asia-Pacific region were included. Low HDL-C (HDL <1.03 mmol/L in men and <1.30 mmol/L in women) was seen among 33.1% (95% confidence interval [CI], 32.9-33.3) of Asians versus 27.0% (95% CI, 26.5-27.5) of non-Asians (P<0.001). The prevalence of low HDL-C in the absence of other lipid abnormalities (isolated low HDL-C) was higher in Asians compared with non-Asians: 22.4% (95% CI, 22.2-22.5) versus 14.5% (95% CI, 14.1-14.9), respectively (P<0.001). During 6.8 years of follow-up, there were 574 coronary heart disease and 739 stroke events. There was an inverse relationship between low HDL-C with coronary heart disease in all individuals (hazard ratio, 1.57; 95% CI, 1.31-1.87). In Asians, isolated low levels of HDL-C were as strongly associated with coronary heart disease risk as low levels of HDL-C combined with other lipid abnormalities (hazard ratio, 1.67 [95% CI, 1.27-2.19] versus 1.63 [95% CI, 1.24-2.15], respectively). There was no association between low HDL-C and stroke risk in this population (hazard ratio, 0.95 [95% CI, 0.78 to 1.17] with nonisolated low HDL-C and 0.81 [95% CI, 0.67-1.00] with isolated low HDL-C).Isolated low HDL-C is a novel lipid phenotype that appears to be more prevalent among Asian populations, in whom it is associated with increased coronary risk. Further investigation into this type of dyslipidemia is warranted.
TCT-142 Prasugrel 5 mg inhibits platelet GPIIb-IIIa and P-Selectin expression in the very elderly - Results from the GENERATIONS trial, a pharmacodynamic study in stable CAD patients
Authors: Henrik wagner, Christian Lood, Catharina Borna, Olof Gidlof, Lennart Truedsson, Chunmei Zhou, Patricia B. Brown, Kenneth J. Winters, Joseph A. Jakubowski, David Erlinge
Journal: Journal of the American College of Cardiology (2013)
Fat Embolism in Patients with Fractured Hips
Authors: S. Sevitt
Journal: BMJ (1972)

Fat embolism was assessed at necropsy and correlated with clinical findings in the patients who died among 854 with fractured hips admitted to hospital between 1967 and August 1971. Sixteen cases of clinical importance were found, eight of which were judged to have been fatal or to have seriously contributed to death. Frequencies were as follows: 2·4 to 3·3% among 424 patients with subcapital fractures; 0·7 to 0·8% in the 405 with trochanteric fractures; 4·1 to 7% among subjects treated without operation, representing 30% of those who died within seven days; and 0·9 to 1·1% among patients treated by pinning, nailing, or nail-plating. The higher frequency in the conservatively treated group is probably related to selection of poor-risk subjects. Fat embolism was found in 6·8 to 8·0% of those with subcapital fractures treated by primary Thompson9s arthroplasty which utilizes acrylic cement, and in none of those given Moore9s prostheses for which cement is not used. Study of a larger group after Moore9s prosthesis is required to establish its lack of special risk. Fat embolism accounted for all the deaths within seven days of Thompson9s arthroplasty and for most within 14 days; it was clearly related to surgery in some cases. A possible explanation of the hazard of Thompson9s arthroplasty is that fat globule entry is enhanced by a rise of intramedullary pressure due to proximal occlusion of the reamed marrow cavity. A controlled trial of the effect of venting the marrow cavity on the frequency of fat embolism is warranted. It is possible that the acrylic monomer may also contribute to venous entry of medullary fat. The higher-age group of those with subcapital fractures and associated chronic cardiac and pulmonary disease might make them more susceptible to fat embolization than those in whom arthroplasty is also carried out for chronic hip disease.
Subchronic Exposure to TCDD, PeCDF, PCB126, and PCB153: Effect on Hepatic Gene Expression
Authors: Chad M. Vezina, Nigel J. Walker, James R. Olson
Journal: Environmental Health Perspectives (2004)

We employed DNA microarray to identify unique hepatic gene expression patterns associated with subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other halogenated aromatic hydrocarbons (HAHs). Female Harlan Sprague-Dawley rats were exposed for 13 weeks to toxicologically equivalent doses of four different HAHs based on the toxic equivalency factor of each chemical: TCDD (100 ng/kg/day), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF; 200 ng/kg/day), 3,3′,4,4′,5-pentachlorobiphenyl (PCB126; 1,000 ng/kg/day), or 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153; 1,000 μg/kg/day). Global gene expression profiles for each exposure, which account for 8,799 gene probe sets contained on Affymetrix RGU34A GeneChips, were compared by principal components analysis. The aryl hydrocarbon receptor (AhR) ligands TCDD, PeCDF, and PCB126 produced very similar global gene expression profiles that were unique from the nonAhR ligand PCB153, underscoring the extensive impact of AhR activation and/or the resulting hepatic injury on global gene expression in female rat liver. Many genes were co-expressed during the 13-week TCDD, PeCDF, or PCB126 exposures, including classical AhR-regulated genes and some genes not previously characterized as being AhR regulated, such as carcinoembryonic-cell adhesion molecule 4 (C-CAM4) and adenylate cyclase-associated protein 2 (CAP2). Real-time reverse-transcriptase polymerase chain reaction confirmed the increased expression of these genes in TCDD-, PeCDF-, and PCB126-exposed rats as well as the up- or down-regulation of several other novel dioxin-responsive genes. In summary, DNA microarray successfully identified dioxin-responsive genes expressed after exposure to AhR ligands (TCDD, PeCDF, PCB126) but not after exposure to the non-AhR ligand PCB153. Together, these findings may help to elucidate some of the fundamental features of dioxin toxicity and may further clarify the biologic role of the AhR signaling pathway.
Hormones in Action
Authors: C. L. Cope
Journal: BMJ (1965)

<b>Objective:</b> To investigate whether the extent of white matter lesions (WML) on fluid attenuated inversion recovery (FLAIR) MRI sequences is an independent risk factor for recurrent stroke, and to document the pattern of acute cerebral infarcts using diffusion weighted imaging (DWI) in patients with different severities of WML. <b>Methods:</b> In a prospective cohort study, 228 consecutive stroke patients were studied between 1999 and 2001 in a community hospital. The severity of WML was graded as 0 (no WML), 1 (mild), 2 (moderate), or 3 (severe) according to the FLAIR appearances. DWI was used to document the location and size of the infarct. <b>Results:</b> 31 patients had grade 0 WML, 69 had grade 1, 59 had grade 2, and 69 had grade 3. Age was independently associated with WML on logistic regression analysis (p = 0.0001). Acute cerebral infarcts in deep white matter were correlated with increasing severity of WML. On a median follow up of 23.0 months, life table analysis showed that recurrent stroke was related to the severity of WML (recurrence rate 7.8% in grade 0, 9.3% in grade 1, 17.7% in grade 2, 43.7% in grade 3; p = 0.0001). Survival was reduced in patients with severe WML (p = 0.0068). A Cox proportional hazards model showed WML to be predictive of recurrent stroke (p = 0.000, hazard ratio = 4.177 (95% confidence interval, 2.038 to 8.564)) and also for survival (p = 0.040, hazard ratio = 2.021 (1.032 to 3.960)). <b>Conclusions:</b> Patients with severe leukoaraiosis have increased risk of deep subcortical stroke and a higher risk of recurrent stroke.
A novel in vitro model for the study of human keratinocyte/leucocyte interactions under autologous conditions
Authors: N. BOYERA, D. CAVEY, F. DELAMADELEINE, M. BOUCLIER, C. HENSBY, B. SHROOT
Journal: British Journal of Dermatology (1993)

Keratinocyte/leucocyte interactions have become an area of intense investigations in the last decade. However, few convenient in vitro models are available at present. We have therefore designed a novel in vitro system for autologous human keratinocyte/leucocyte co-culture. Non-invasive epidermal cell sampling was achieved by using outer root sheath cells from hair follicles. After one passage, pure keratinocyte cultures (no Langerhans cells or melanocytes) were obtained. Co-culture experiments were performed on a Transwell system: keratinocytes were grown on the porous cupula, and then laid on to wells containing leucocytes. Alternatively, leucocytes can be added to the cupula when contact interactions between the two cell types are to be investigated. Using this system, we demonstrated that Phaesolus vulgaris phytohaemagglutinin-activated T lymphocytes (with 10% monocytes) in the lower compartment induced intercellular adhesion molecule 1 (ICAM-1) and HLA-DR expression, and inhibited methyl-3H-thymidine incorporation in normal human autologous keratinocytes cultured on the cupula. These changes were mediated by soluble factors (no cell contacts between keratinocytes and leucocytes), and required lymphocyte activation. This is the first direct in vitro evidence for leucocyte-induced ICAM-1 and HLA-DR expression on keratinocytes. This system is a potential tool for the study of keratinocyte/leucocyte interactions.(ABSTRACT TRUNCATED AT 250 WORDS)