tbuckley/cabot-search huggingface dataset:
Isoform level expression profiles provide better cancer signatures than gene level expression profiles
Authors: ZhongFa Zhang, Sharmistha Pal, Yingtao Bi, Julia Tchou, Ramana V Davuluri
Journal: Genome Medicine (2013)

Abstract Background The majority of mammalian genes generate multiple transcript variants and protein isoforms through alternative transcription and/or alternative splicing, and the dynamic changes at the transcript/isoform level between non-oncogenic and cancer cells remain largely unexplored. We hypothesized that isoform level expression profiles would be better than gene level expression profiles at discriminating between non-oncogenic and cancer cellsgene level. Methods We analyzed 160 Affymetrix exon-array datasets, comprising cell lines of non-oncogenic or oncogenic tissue origins. We obtained the transcript-level and gene level expression estimates, and used unsupervised and supervised clustering algorithms to study the profile similarity between the samples at both gene and isoform levels. Results Hierarchical clustering, based on isoform level expressions, effectively grouped the non-oncogenic and oncogenic cell lines with a virtually perfect homogeneity-grouping rate (97.5%), regardless of the tissue origin of the cell lines. However, gene levelthis rate was much lower, being 75% at best based on the gene level expressions. Statistical analyses of the difference between cancer and non-oncogenic samples identified the existence of numerous genes with differentially expressed isoforms, which otherwise were not significant at the gene level. We also found that canonical pathways of protein ubiquitination, purine metabolism, and breast-cancer regulation by stathmin1 were significantly enriched among genes thatshow differential expression at isoform level but not at gene level. Conclusions In summary, cancer cell lines, regardless of their tissue of origin, can be effectively discriminated from non-cancer cell lines at isoform level, but not at gene level. This study suggests the existence of an isoform signature, rather than a gene signature, which could be used to distinguish cancer cells from normal cells.
MHC II tetramers visualize human CD4+ T cell responses to Epstein–Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response
Authors: Heather M. Long, Odette L. Chagoury, Alison M. Leese, Gordon B. Ryan, Eddie James, Laura T. Morton, Rachel J.M. Abbott, Shereen Sabbah, William Kwok, Alan B. Rickinson
Journal: The Journal of Experimental Medicine (2013)

Virus-specific CD4+ T cells are key orchestrators of host responses to viral infection yet, compared with their CD8+ T cell counterparts, remain poorly characterized at the single cell level. Here we use nine MHC II–epitope peptide tetramers to visualize human CD4+ T cell responses to Epstein–Barr virus (EBV), the causative agent of infectious mononucleosis (IM), a disease associated with large virus-specific CD8+ T cell responses. We find that, while not approaching virus-specific CD8+ T cell expansions in magnitude, activated CD4+ T cells specific for epitopes in the latent antigen EBNA2 and four lytic cycle antigens are detected at high frequencies in acute IM blood. They then fall rapidly to values typical of life-long virus carriage where most tetramer-positive cells display conventional memory markers but some, unexpectedly, revert to a naive-like phenotype. In contrast CD4+ T cell responses to EBNA1 epitopes are greatly delayed in IM patients, in line with the well-known but hitherto unexplained delay in EBNA1 IgG antibody responses. We present evidence from an in vitro system that may explain these unusual kinetics. Unlike other EBNAs and lytic cycle proteins, EBNA1 is not naturally released from EBV-infected cells as a source of antigen for CD4+ T cell priming.
High-frequency, precise modification of the tomato genome
Authors: Tomáš Čermák, Nicholas J. Baltes, Radim Čegan, Yong Zhang, Daniel F. Voytas
Journal: Genome biology (2015)

The use of homologous recombination to precisely modify plant genomes has been challenging, due to the lack of efficient methods for delivering DNA repair templates to plant cells. Even with the advent of sequence-specific nucleases, which stimulate homologous recombination at predefined genomic sites by creating targeted DNA double-strand breaks, there are only a handful of studies that report precise editing of endogenous genes in crop plants. More efficient methods are needed to modify plant genomes through homologous recombination, ideally without randomly integrating foreign DNA. Here, we use geminivirus replicons to create heritable modifications to the tomato genome at frequencies tenfold higher than traditional methods of DNA delivery (i.e., Agrobacterium). A strong promoter was inserted upstream of a gene controlling anthocyanin biosynthesis, resulting in overexpression and ectopic accumulation of pigments in tomato tissues. More than two-thirds of the insertions were precise, and had no unanticipated sequence modifications. Both TALENs and CRISPR/Cas9 achieved gene targeting at similar efficiencies. Further, the targeted modification was transmitted to progeny in a Mendelian fashion. Even though donor molecules were replicated in the vectors, no evidence was found of persistent extra-chromosomal replicons or off-target integration of T-DNA or replicon sequences. High-frequency, precise modification of the tomato genome was achieved using geminivirus replicons, suggesting that these vectors can overcome the efficiency barrier that has made gene targeting in plants challenging. This work provides a foundation for efficient genome editing of crop genomes without the random integration of foreign DNA.
Bromocriptine induced pleuropulmonary fibrosis.
Authors: J Wiggins, C Skinner
Journal: Thorax (1986)

Bromocriptine is an ergot derivative with dopaminergic properties that is of value in the treatment of Parkinsonism.The development of pleuropulmonary fibrosis during treat- ment with bromocriptine has been reported,' 4 but a causal relationship has been questioned.5 6 We describe a patient who developed a systemic illness, including pleuro- pulmonary fibrosis, during treatment with bromocriptine for Parkinsonism, and in whom cessation of the drug was followed by weight gain, reversal of anaemia, a fall in the raised serum IgG concentration and erythrocyte sedimentation rate, and disappearance of neutrophil leucocytosis in lung lavage fluid, strongly supporting a causal relationship with bromocriptine.
Regional differences in utilization of implantable cardioverter/defibrillators - an Antiarrhythmics Versus Implantable Defibrillators (AVlD) registry study
Authors: H.-T. Shih, D.G. Wyse, C. Rizo-Patron, N.J. Stamato, J.P. Daubert, S. Lancaster, E.G. Renfroe, N. Connors, A. Pacifico, B. Crevey, C. Jennings, D. Whiting, Q. Yao
Journal: Journal of the American College of Cardiology (1998)
Subcuticular sutures versus staples for skin closure after open gastrointestinal surgery: a phase 3, multicentre, open-label, randomised controlled trial
Authors: Toshimasa Tsujinaka, Kazuyoshi Yamamoto, Junya Fujita, Shunji Endo, Junji Kawada, Shin Nakahira, Toshio Shimokawa, Shogo Kobayashi, Makoto Yamasaki, Yusuke Akamaru, Atsushi Miyamoto, Tsunekazu Mizushima, Junzo Shimizu, Koji Umeshita, Toshinori Ito, Yuichiro Doki, Masaki Mori
Journal: The Lancet (2013)
Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction.
Authors: Y Nio, H Matsubara, S Murasawa, M Kanasaki, M Inada
Journal: Journal of Clinical Investigation (1995)

Increasing evidence suggests that angiotensin II (AngII) acts as a modulator for ventricular remodeling after myocardial infarction. Using competitive reverse-transcriptase polymerase chain reaction, nuclear runoff, and binding assays, we examined the regulation of AngII type 1a and 1b (AT1a-R and AT1b-R) and type 2 receptor (AT2-R) expression in the infarcted rat heart as well as the effects of AngII receptor antagonists. AT1a-R mRNA levels were increased in the infarcted (4.2-fold) and noninfarcted portions (2.2-fold) of the myocardium 7 d after myocardial infarction as compared with those in sham-operated controls, whereas AT1b-R mRNA levels were unchanged. The amount of detectable AT2-R mRNA increased in infarcted (3.1-fold) and noninfarcted (1.9-fold) portions relative to that in the control. The transcription rates for AT1a-R and AT2-R genes, determined by means of a nuclear runoff assay, were significantly increased in the infarcted heart. The AngII receptor numbers were elevated (from 12 to 35 fmol/mg protein) in the infarcted myocardium in which the increases in AT1-R and AT2-R were 3.2- and 2.3-fold, respectively, while the receptor affinity was unchanged. Therapy with AT1-R antagonist for 7 d reduced the increase in AT1-R and AT2-R expressions in the infarcted heart together with a decrease in blood pressure, whereas therapy with an AT2-R antagonist did not affect mRNA levels and blood pressure. Neither AT1-R nor AT2-R antagonists affected the infarct sizes. These results demonstrated that myocardial infarction causes an increase in the gene transcription and protein expression of cardiac AT1a-R and AT2-R, whereas the AT1b-R gene is unaffected, and that therapy with an AT1-R antagonist, but not with an AT2-R antagonist, is effective in reducing the increased expression of AngII receptor subtypes induced by myocardial infarction.
In Silico Predicted Robustness of Viroid RNA Secondary Structures. II. Interaction between Mutation Pairs
Authors: R. Sanjuan
Journal: Molecular Biology and Evolution (2006)

Viroids are plant subviral pathogens whose genomes are constituted by a single-stranded and covalently closed small RNA molecule that does not encode for any protein. Most of the 29 described viroid species fold into a rodlike or quasi-rodlike structure, whereas a few of them fold as highly branched structures. In a previous study, we used RNA thermodynamic secondary structure prediction algorithms to compare the mutational robustness of all viroid species. Here we used the same approach to explore the sign and strength of epistasis among pairs of random mutations. We found that antagonistic interactions were more abundant than synergistic ones. However, despite their lower frequency, synergistic interactions tended to be more intense. Mutational robustness and the intensity of epistasis were correlated such that viroid species with large average mutational effects showed stronger antagonistic epistasis, whereas viroids with mild average mutational effects showed weaker antagonistic interactions. The strength of antagonistic epistasis decreased with genome complexity as a consequence of the gained robustness of duplicated genomes. In good agreement with our previous finding of an evolutionary trend toward increased robustness, we now found a trend toward reduced antagonistic epistasis.
Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review
Authors: G. Kaur, E. T. Sayegh, A. Larson, O. Bloch, M. Madden, M. Z. Sun, I. J. Barani, C. D. James, A. T. Parsa
Journal: Neuro-Oncology (2014)

Atypical meningiomas (AMs) and malignant meningiomas (MMs) are tumors with a lower incidence and poorer prognosis than benign meningiomas. The role of radiotherapy as an adjuvant to surgical resection, especially for AMs, is incompletely defined. In this study, the English-language literature was systematically reviewed for studies that reported tumor characteristics, treatment parameters, and clinical outcomes after adjuvant radiotherapy for AM and MM, including overall survival, progression-free survival, and/or time to recurrence or mortality. Clinical outcomes were further assessed in the context of resection status, timing of administration, and radiation dose. Outcomes after stereotactic radiosurgery were also examined. Treatment toxicity and other potential prognostic or confounding factors were appraised. Ten and 11 studies for AM and MM, respectively, met the inclusion criteria. The median 5-year progression-free survival and overall survival after adjuvant radiotherapy were 54.2% and 67.5%, respectively, for AM and 48% and 55.6% for MM. The complication rates were 11.1% for AM and 5.1% for MM. Incomplete resection and radiation dose <50 Gy conferred significantly poorer 5-year progression-free survival. Most studies were unable to demonstrate a statistically significant prognostic benefit for adjuvant radiotherapy in AM. In conclusion, adjuvant radiotherapy significantly improved local control of AMs and MMs, especially after subtotal resection. Study limitations, including inadequate statistical power, may underlie the studies' inability to demonstrate a statistically significant benefit for adjuvant radiotherapy in AM. Because these tumors preferentially recur within 5 years of surgical resection, future studies should define whether early adjuvant therapy should become part of the standard treatment paradigm for completely excised tumors.
ORAL IMMUNIZATION AGAINST PNEUMOCOCCI
Journal: JAMA (1930)

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
Exogenous Reinfection with Tuberculosis on a European Island with a Moderate Incidence of Disease
Authors: JOSÉ A. CAMINERO, MARÍA J. PENA, MARÍA I. CAMPOS-HERRERO, JOSÉ C. RODRÍGUEZ, OCTAVIO AFONSO, CARLOS MARTIN, JOSÉ M. PAVÓN, MARÍA J. TORRES, MARCOS BURGOS, PEDRO CABRERA, PETER M. SMALL, DONALD A. ENARSON
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The frequency and determinants of exogenous reinfection and of endogenous reactivation of tuberculosis in patients previously treated are poorly understood. In Gran Canaria Island, Spain, between 1991 and 1996, 962 tuberculosis cases were confirmed by culture. Drug susceptibility testing was performed on available bacterial isolates and IS6110-based RFLP genotyping was carried out. Twenty-three patients (2.4%) had two positive cultures separated by at least 12 mo, 18 of whom had bacterial DNA available for genotypic analysis. The initial and final isolates from eight (44%) were different genotypes, indicating exogenous reinfection. Six of them were retreated after cure and two retreated after default. Six were HIV seronegative and two were HIV seropositive. Endogenous reactivation was seen in the remaining 10 patients of whom eight were retreated after default and two after cure. Three of the eight (38%) being retreated after default developed multidrug resistance. One genotype was responsible for a second episode of tuberculosis in five cases, three exogenous reinfections and two endogenous reactivations. In the context of a moderate incidence of tuberculosis, exogenous reinfection is an important cause of TB recurrence, even in HIV-seronegative patients.
Attempts at estimating mixed venous carbon dioxide tension by the single-breath method
Authors: H Ohta, O Takatani, T Matsuoka
Journal: European Respiratory Journal (1989)

The single-breath method was originally proposed by Kim et al. [1] for estimating the blood carbon dioxide tension and cardiac output. Its reliability has not been proven. The present study was undertaken, using dogs, to compare the mixed venous carbon dioxide tension (PVCO2) calculated by the single-breath method with the PVCO2 measured in mixed venous blood, and to evaluate the influence of variations in the exhalation duration and the volume of expired air usually discarded from computations as the deadspace. Among the exhalation durations of 15, 30 and 45 s tested, the 15 s duration was found to be too short to obtain an analyzable O2-CO2 curve, but at either 30 or 45 s, the calculated values of PVCO2 were comparable to the measured PVCO2. A significant agreement between calculated and measured PVCO2 was obtained when the expired gas with PCO2 less than 22 Torr was considered as deadspace gas.
CAGE-TSSchip: promoter-based expression profiling using the 5'-leading label of capped transcripts
Authors: Shintaro Katayama, Mutsumi Kanamori-Katayama, Kazumi Yamaguchi, Piero Carninci, Yoshihide Hayashizaki
Journal: Genome biology (2007)

Abstract Cap analysis gene expression (CAGE) technology has revealed numerous transcription start sites (TSSs) in mammals and has suggested complex promoter-based patterns of regulation. We developed the CAGE-TSSchip to detect promoter-based transcriptional activity. The CAGE-TSSchip is a customized oligonucleotide array that targets known TSSs identified by CAGE. A new labeling method, labeling capped transcripts from the 5'-end, had to be developed. The CAGE-TSSchip is accurate and sensitive, and represents the activity of each TSS.
Attenuation of microRNA-126 Expression That Drives CD34+38− Stem/Progenitor Cells in Acute Myeloid Leukemia Leads to Tumor Eradication
Authors: David C. de Leeuw, Fedor Denkers, Marjolein C. Olthof, Arjo P. Rutten, Walter Pouwels, Gerrit Jan Schuurhuis, Gert J. Ossenkoppele, Linda Smit
Journal: Cancer Research (2014)

Despite high remission rates after therapy, 60% to 70% of patients with acute myeloid leukemia (AML) do not survive 5 years after their initial diagnosis. The main cause of treatment failures may be insufficient eradication of a subpopulation of leukemic stem-like cells (LSC), which are thought to be responsible for relapse by giving rise to more differentiated leukemic progenitors (LP). To address the need for therapeutic targets in LSCs, we compared microRNA (miRNA) expression patterns in highly enriched healthy CD34(+)CD38(-) hematopoietic stem cells (HSC), CD34(+)CD38(-) LSCs, and CD34(+)CD38(+) LPs, all derived from the same patients' bone marrow (BM) specimens. In this manner, we identified multiple differentially expressed miRNAs, in particular miR-126, which was highly expressed in HSCs and increased in LSCs compared with LPs, consistent with a stem-like cell function. High miR-126 expression in AML was associated with poor survival, higher chance of relapse, and expression of genes present in LSC/HSC signatures. Notably, attenuating miR-126 expression in AML cells reduced in vitro cell growth by inducing apoptosis, but did not affect the survival of normal BM in which it instead enhanced expansion of HSCs. Furthermore, targeting miR-126 in LSCs and LPs reduced their clonogenic capacity and eliminated leukemic cells, again in the absence of similar inhibitory effects on normal BM cells. Our results define miR-126 as a therapeutic focus to specifically eradicate LSCs and improve AML outcome.
Risk factors of treatment failure in community acquired pneumonia: implications for disease outcome
Authors: R Menendez
Journal: Thorax (2004)

AIMS: To determine whether nontransferrin bound iron is present in the serum of long term survivors of acute leukaemia and bone marrow transplantation who have liver dysfunction as indicated by consistently raised serum aspartate aminotransferase (AST) activities. METHODS: Thirty eight patients, who were at least three years from the end of treatment, were studied. Serum samples were analysed for hepatitis C, hepatitis B, AST, ferritin, and non-transferrin bound iron. A bleomycin based assay was used to detect non-transferrin bound iron. Patient and blood bank records were examined to determine the number of units of transfused blood received by each patient. RESULTS: Ten patients had consistently raised serum AST activities. Of these, two had evidence of hepatitis C infection, one had chronic hepatitis B infection and one had chronic graft versus host disease affecting the liver. None of these four patients had detectable non-transferrin bound iron. The remaining six patients had no obvious reason for raised AST activities, but four had non-transferrin bound iron detectable in their serum as compared with only two out of 28 patients with normal AST activities. Patients with abnormal AST activities had higher serum ferritin concentrations than those with normal AST, though serum ferritin was raised in 21 of 28 patients without liver dysfunction. CONCLUSION: Non-transferrin bound iron may be found in this group of patients, suggesting that iron overload is the cause of the observed liver dysfunction. Non-transferrin bound iron may also be a more specific indicator of iron overload than the serum ferritin concentrations.
Michael Ievers Cox
Authors: N. C. J. Cox
Journal: BMJ (2014)

Despite being brought up in London, Michael Ievers Cox was a countryman at heart. As a student at St Thomas’ during the second world war, he kept a ferret in his locker. Food was rationed, so he and a friend sailed a small open dinghy from the hospital to the Thames estuary to shoot duck for the pot. They also poached fallow deer in Kent, returning to London on a motorbike with the deer sitting upright between them.

As a student he volunteered to serve in the …
The Changing Aetiology of Heart Disease
Authors: W. M. Arnott
Journal: BMJ (1954)

Until very recently it was customary to classify heart disease under such structural headings as " aortic in- competence," "mitral stenosis," or " pericarditis."The last few decades have seen the development of knowledge of disordered function as well as of structure.The most satisfactory classifications of disease are those which are based on causes, for the good reason that effective prevention depends on knowledge of aetiology.At once, of course, one is up against the problem of