tbuckley/cabot-search huggingface dataset:
999. siRNA-Mediated Interference of Double-Stranded RNA Binding Protein [E3L] Is an Effective Strategy to Inhibit Vaccinia Virus
Authors: Dave S. Rajnish, James P. McGettigan, Giuseppe Nunnari, Matthias J. Schnell, Roger J. Pomerantz
Journal: Molecular Therapy (2005)

Top of pageAbstract
Background: The Vaccinia virus E3L Interferon resistance gene encodes a 25kDa polypeptide which is synthesized early during the viral infection cycle. The polypeptide binds dsRNA and thus competes with the N-terminal dsRNA binding domain of protein kinase. This prevents PKR activation. However, siRNA-mediated down-regulation of E3L is hypothesized to eliminate the competition for dsRNA in favor of protein kinase leading to its activation and the subsequent cascade that establishes the anti-viral state.

Methods: RNA interference (RNAi), a natural biological phenomenon mediated by small interfering RNA (siRNA) molecules, has been demonstrated to be an effective anti-viral strategy. However, no study thus far has utilized this emerging technology for Vaccinia virus, which is a useful surrogate for the Smallpox virus. In this study, we have used 21bp chemically synthesized siRNA duplexes whose sequences are derived from the E3L region of the Vaccinia genome and are conserved in smallpox and related poxviruses. Viral replication was assessed by measuring the |[beta]|-galactosidase activity in extracts prepared from infected HeLa cells. A recombinant strain of Vaccinia WR virus carrying the indicator gene was used. Production of infectious virus particles was measured by a plaque assay. Sonicated extracts from infected HeLa cells were used to quantify the amount of plaques generated on BSC-1 cells.

Results: E3L-specific siRNAs exerted a potent antiviral effect on Vaccinia virus [WR] replication. Viral levels were reduced to below detection limits [MOI=0.01pfu/cell] and 7.6% of control infection [MOI=0.1pfu/cell]. Strong inhibition was observed even at extreme viral loads [15-30% of control infection at MOI=0.1-0.4pfu/cell]. Of the four E3L-specific siRNAs, E3L-C siRNA had the strongest effect [3.5% of control infection at MOI=0.1pfu/cell] followed by E3L-A siRNA [17.2% of control at MOI=0.1pfu/cell]. Silencing of E3L leads to a reduced production of infectious viral particles as well. When all the four E3L-specific siRNAs were multiplexed, infectious viral production was reduced to 4.5% of control infection [MOI=0.1].

Conclusions: The immediate potential use of the E3L-specific siRNA is as a biodefense tool against smallpox. These molecules seem to have a therapeutic potential that might be superior to the existing vaccination alternative. The value of these molecules has to be assessed in light of the morbidity associated with the small pox vaccine and potential complications that might be of concern for the immunocompromised population. Since dsRNA plays a crucial role in the generation of the antiviral state, the above described siRNA will be useful for dissecting the molecular mechanisms associated with this phenomenon.
Synergism between gamma interferon and lipopolysaccharide for synthesis of factor B, but not C2, in human fibroblasts.
Authors: Y Katz, F S Cole, R C Strunk
Journal: The Journal of Experimental Medicine (1988)

Four different human fibroblast cell lines synthesized C2 and factor B. Factor B synthesis was increased 12.1-fold by 50 ng/ml LPS and 7.1-fold by 100 U/ml IFN-gamma. C2 synthesis was increased only 2.1-fold by LPS, but 6.4-fold by IFN-gamma. Both LPS and IFN-gamma increased levels of factor B mRNA. LPS induced a 4.7-fold greater increase in factor B protein than in factor B mRNA, whereas IFN-gamma stimulated comparable increases in protein and mRNA. These data suggest that LPS acts to increase factor B synthesis at both pretranslational and translational sites, while IFN-gamma acts primarily at a pretranslational level. In contrast to factor B, increases in C2 protein and C2 mRNA were comparable for both stimuli. A synergistic effect between the two stimuli was observed for factor B only: protein synthesis was increased 54.5-fold or 2.8-fold greater than the additive effects of the stimuli separately. The rate of synthesis in the presence of LPS and IFN-gamma together could not be achieved by increasing concentrations of, or the times of incubation with, either stimulus separately. The synergism was not the result of an increased sensitivity of the cells to either stimulus and was not reproduced by preincubation with one stimulus before incubation with the other stimulus. Several lines of evidence suggest that the synergism, like the stimulation of factor B synthesis by LPS, was dependent on both translational and pretranslational regulation of factor B mRNA. C2 and factor B synthesized in human fibroblasts may play a role in host defense in inflammatory reactions before increases in vascular permeability and recruitment of other complement producing cells.
A miniature Wright peak-flow meter.
Authors: B M Wright
Journal: BMJ (1978)

A new miniature Wright peak-flow meter has been designed and produced. The meter is tubular with a spring-loaded piston and a longitudinal slot through which air escapes. Its dynamic characteristics have been carefully designed to make it respond only to peak flow and not to rate of rise. Performance tests on early instruments showed fairly close correlation with the Wright peak-flow meter but with a constant error of + 38 1/min. On later models the correlation was increased to 0.990 and the error reduced to + 3%. The mini-meter correlates as well with the standard instrument as two standard instruments correlate with each other and should prove useful clinically.
'Illegitimate' Is Not Legitimate
Authors: Richard G. Van Dellen
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The editorial by Dr Sell and Mr Krause referred to children born out of wedlock as illegitimate. Although the purpose of the editorial is laudable, the term "illegitimate" to refer to such children is both inaccurate and prejudicial. These children are born by the same legitimate process as are all children. Children have no choice as to the circumstance of their birth. Pearl Buck wrote years ago, There is no such person as an illegitimate child and this has often been truly said. He [or she] appears according to the laws of nature. What is illegitimate is the condemning environment into which he [or she] is born.<sup>1</sup> Let's continue to work to improve that environment.
Molecular phylogeny of the genus Hypochaeris using internal transcribed spacers of nuclear rDNA: inference for chromosomal evolution
Authors: M. Cerbah, T. Souza-Chies, M. F. Jubier, B. Lejeune, S. Siljak-Yakovlev
Journal: Molecular Biology and Evolution (1998)

Sequences of the internal transcribed spacers (ITSs) of 18S-26S nuclear ribosomal DNA were used to resolve phylogenetic relationships and chromosomal evolution among 14 species of the genus Hypochaeris (Asteraceae). Parsimony analysis was performed for phylogenetic reconstruction, and sequence divergence between species was estimated. Pairwise sequence divergence within Hypochaeris genus ranged from 0% to 25.68% in ITS1 and from 0% to 17.08% in ITS2. A highly resolved strict-consensus tree was obtained that showed the phylogenetically useful information of ITS sequences within the genus Hypochaeris. Four clades could be well distinguished, one of them formed by the single species H. robertia, which appeared to be the most related to the ancestral species of the genus. The results agree with taxonomic classification based on morphological data, and the tree obtained, when indels are coded as missing data, aggregates the species having the same chromosome number, except in one clade. According to the ITS phylogenetic tree, the chromosomal evolution within the genus Hypochaeris conflicts with the previous hypothesis and suggests that karyotype evolution in Hypochaeris was accompanied with both decreasing and increasing dysploidy, probably with several chromosomal rearrangements, and from an ancestral basic chromosome number of 4 or 5.
Reanalyses of Trial Results
Authors: Timothy F. Platts-Mills, Christopher W. Jones
Journal: JAMA (2015)

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
Aspirin to Prevent Arterial Thrombosis
Authors: Edwin W. Salzman
Journal: New England Journal of Medicine (1982)

More than 10 years have elapsed since the Journal first published the results of a clinical trial of the use of aspirin to prevent thrombosis.1 The possibility that aspirin might have an antithrombotic effect was an obvious corollary to the demonstration2 that it inhibited platelet function by blocking the enzyme cyclooxygenase, which converts arachidonic acid to prostaglandin endoperoxides and ultimately to the powerful platelet stimulant thromboxane A2. Because of the prevalence of venous thrombosis and the availability of sensitive methods for its diagnosis, early studies of aspirin examined its use in this disorder, even though it was recognized . . .
Epigallocatechin gallate induces apoptosis of monocytes
Authors: Kazushige Kawai, Nelson H. Tsuno, Joji Kitayama, Yurai Okaji, Kentaro Yazawa, Masahiro Asakage, Shin Sasaki, Toshiaki Watanabe, Koki Takahashi, Hirokazu Nagawa
Journal: Journal of Allergy and Clinical Immunology (2005)
Association Of Wheezing Illness With Respiratory Viruses In Hospitalized Jordanian Children
Authors: Olajumoke Fadugba, Eva Kathryn Miller, Najwa Khuri-Bulos, Samir Faouri, Asem Shehabi, Christopher Fonnesbeck, Li Wang, John V. Williams, Natasha Halasa
Journal: Journal of Allergy and Clinical Immunology (2014)
Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development.
Authors: A R Ramiro, C Trigueros, C Márquez, J L San Millán, M L Toribio
Journal: The Journal of Experimental Medicine (1996)

In murine T cell development, early thymocytes that productively rearrange the T cell receptor (TCR) beta locus are selected to continue maturation, before TCR alpha expression, by means of a pre-TCR alpha- (pT alpha-) TCR beta heterodimer (pre-TCR). The aim of this study was to identify equivalent stages in human thymocyte development. We show here that variable-diversity-joining region TCR beta rearrangement and the expression of full-length TCR beta transcripts have been initiated in some immature thymocytes at the TCR alpha/beta- CD4+CD8- stage, and become common in a downstream subset of TCR alpha/beta- CD4+CD8+ thymocytes that is highly enriched in large cycling cells. TCR beta chain expression was hardly detected in TCR alpha/beta- CD4+CD8- thymocytes, whereas cytoplasmic TCR beta chain was found in virtually all TCR alpha/beta- CD4+CD8+ blasts. In addition, a TCR beta complex distinct from the mature TCR alpha/beta heterodimer was immunoprecipitated only from the latter subset. cDNA derived from TCR alpha/beta- CD4+CD8+ blasts allowed us to identify and clone the gene encoding the human pT alpha chain, and to examine its expression at different stages of thymocyte development. Our results show that high pT alpha transcription occurs only in CD4+CD8- and CD4+CD8+ TCR alpha/beta- thymocytes, whereas it is weaker in earlier and later stages of development. Based on these results, we propose that the transition from TCR alpha/beta- CD4+CD8- to TCR alpha/beta- CD4+CD8+ thymocytes represents a critical developmental stage at which the successful expression of TCR beta promotes the clonal expansion and further maturation of human thymocytes, independent of TCR alpha.
THE EFFECT OF DIET ON THE SUSCEPTIBILITY OF THE MOUSE TO PNEUMONIA VIRUS OF MICE (PVM)
Authors: William B. Leftwich, George S. Mirick
Journal: The Journal of Experimental Medicine (1949)

Young mice fed diets deficient in pyridoxine or fed desoxypyridoxine after the inoculation of the pneumonia virus of mice were more resistant to infection than well nourished controls. The susceptibility of young mice to PVM increased with the duration of pyridoxine administration after inoculation. Dietary protein restriction when pyridoxine was provided did not affect the susceptibility of mice to PVM. The PVM-combining capacity of mouse lung and the titer of humoral antibody against PVM were the same in mice fed a complete or pyridoxine-deficient diet for 6 days. The amount of PVM in mouse lungs 6 days after inoculation was greater by both infectivity and hemagglutination titrations in mice fed pyridoxine than in pyridoxine-deficient controls. This suggests that pyridoxine was essential during the postinoculation period for optimal virus multiplication.
Abstract 3394: Identification of PRDX4 and P4HA2 as metastasis-associated proteins in oral cavity squamous cell carcinoma by comparative tissue proteomics of microdissected specimens using iTRAQ technology
Authors: Kai-Ping Chang, Yu-Sun Chang, Jau-Song Yu, Lang-Ming Chi
Journal: Cancer Research (2012)

Abstract Background Cervical lymph node metastasis represents the major prognosticator for oral cavity squamous cell carcinoma (OSCC). Methods Here, we used an iTRAQ-based quantitative proteomic approach to identify proteins that are differentially expressed between microdissected primary and metastatic OSCC tumors. The selected candidates were examined in tissue sections via immunohistochemistry, and their roles in OSCC cell function investigated using RNA interference. Results Seventy-four differentially expressed proteins in nodal metastases, including PRDX4 and P4HA2, were identified. Immunohistochemical analysis revealed significantly higher levels of PRDX4 and P4HA2 in tumor cells than adjacent non-tumor epithelia (P &amp;lt; 0.0001 and P &amp;lt; 0.0001, respectively), and even higher expression in the 31 metastatic tumors of lymph nodes, compared to the corresponding primary tumors (P = 0.060 and P &amp;lt; 0.0001, respectively). Overexpression of PRDX4 and P4HA2 was significantly associated with positive pN status (P = 0.048 and P = 0.041, respectively). PRDX4 overexpression was a significant prognostic factor for disease-specific survival in both univariate and multivariate analyses (P = 0.034 and P = 0.032, respectively). Additionally, cell migration and invasiveness were attenuated in OEC-M1 cells upon in vitro knockdown of PRDX4 and P4HA2 with specific interfering RNA. Conclusions Novel metastasis-related prognostic markers for OSCC could be identified by our approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3394. doi:1538-7445.AM2012-3394
The Use of Endoscopic Ultrasonography in the Diagnosis and Staging of Carcinoma of the Papilla of Vater
Authors: K. Yasuda, H. Mukai, E. Cho, M. Nakajima, K. Kawai
Journal: Endoscopy (1988)

Endoscopic ultrasonography (EUS) was evaluated in the diagnosis of carcinoma of the papilla of Vater. Thirteen cases of carcinoma of the papilla examined by EUS were investigated with the aim of assessing the detection capability of EUS in comparison with other diagnostic tools, and its usefulness in diagnosing the extent of the tumor.
Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse
Authors: Enhui Pan, Xiao-an Zhang, Zhen Huang, Artur Krezel, Min Zhao, Christine E. Tinberg, Stephen J. Lippard, James O. McNamara
Journal: Neuron (2011)
Predicting survival for myeloid leukemia after HLA-identical sibling donor allogeneic stem cell transplantation
Authors: D Gallardo, R De la Cámara, A Torres, S Brunet, A Jiménez, J C Vallejo, G Sanz, D Serrano, E Carreras, C Martín, C Sanz-Rodríguez, J Sierra, I Espigado, D Caballero, J J Berlanga
Journal: Leukemia (2004)
The Discovery of the Art of the Insane
Authors: John E. Gedo
Journal: JAMA (1990)

This beautifully produced and illustrated volume starts out as a brilliant piece of intellectual history. It describes the evolution of psychiatric hospitals over the past 250 years that fostered the image-making activities of inmates in the recovery phase of psychotic decompensations. The contributions of Pinel, Tuke, and Benjamin Rush in revolutionizing the care of such unfortunates in the direction of humane treatment led to policies that encouraged patients' constructive activities, which often focused on producing "art." Although previously untrained persons created images in the manner of naive artists, the occasional professional who became psychotic (like the British painter Richard Dadd) produced work of undoubted distinction in the asylum. MacGregor also traces the increasing interest on the part of the art establishment in portraying the world of the mental hospital—a development for which Hogarth, Goya, Fuseli, and Gericault deserve major credit. In parallel with this progressive tendency, the psychiatric world began
Acute Phlegmonous Caecitis
Authors: R. F. Shove
Journal: BMJ (1950)

Rationale: IL-13 and TGF-β have been shown to affect expression of calcium handling proteins in airway smooth muscle (ASM). We hypothesise they also alter expression of TRPC6 channel proteins. Methods: Cultured ASM cells were serum starved for 72h before treatment. SMAD2 and SMAD3 siRNAs were transfected using AmaxaTM nucleofector (Lonza). Protein expression was measured via western blots, and intracellular calcium with Fura3-PE/AM. Results: Treatment of ASM cells for 1 week with TGF-β (10ng/ml) increased TRPC6 protein (285 ± 48% n=17 p&lt;0.001); IL-13 (10ng/ml) had no additional effect (279 ± 37% n=17 p&lt;0.001). TRPC6 splice variants were non-uniformly affected; a 75kDa variant increased by 720 ± 196 % (p=0.02) whereas the functional ∼100kDa variants increased by 185 ± 20 % (p=0.003). Knockdown of SMAD2 or 3 abolished the increase. TGF-β significantly reduced SMAD3 protein (p&lt;0.001, n=7). Following treatment with TGF-β, elevation in calcium elicited by bradykinin (0.5μM) or the TRPC6 agonist flufenamic acid (10uM) was decreased at 72 hours (p=0.02, n=7-8) and 1 week (p=0.002, n=4-5). Conclusions: TGF-β but not IL-13 results in differential increases in TRPC6 splice variant expression, regulated by SMAD2/3. As this was accompanied by reduced calcium mobilisation, we speculate increased expression of non-functional TRPC6 variants may contribute to impaired calcium handling in asthma.
Single parents need home visits by health visitors
Authors: J. R Edwards
Journal: BMJ (1998)

EDITOR—Fleming and Charlton have shown that children of single parents receive fewer immunisations and have more accidents than children in other households.1 Both of these areas are regarded as priorities for intervention by community services undertaking child health surveillance,2 and Fleming and Charlton consider that single parents should be particularly targeted.

I have undertaken a survey of baby clinics run by health visitors …
A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study
Authors: Shuichi Miyawaki, Shigeki Ohtake, Shin Fujisawa, Hitoshi Kiyoi, Katsuji Shinagawa, Noriko Usui, Toru Sakura, Koichi Miyamura, Chiaki Nakaseko, Yasushi Miyazaki, Atsushi Fujieda, Tadashi Nagai, Takahisa Yamane, Masafumi Taniwaki, Masatomo Takahashi, Fumiharu Yagasaki, Yukihiko Kimura, Norio Asou, Hisashi Sakamaki, Hiroshi Handa, Sumihisa Honda, Kazunori Ohnishi, Tomoki Naoe, Ryuzo Ohno
Journal: Blood (2010)
Second generation endometrial ablation techniques for heavy menstrual bleeding: network meta-analysis
Authors: J. P. Daniels, L. J. Middleton, R. Champaneria, K. S. Khan, K. Cooper, B. W. J. Mol, S. Bhattacharya
Journal: BMJ (2012)

<b>Objective</b> To determine the relative effectiveness of second generation ablation techniques in the treatment of heavy menstrual bleeding. <b>Design</b> Network meta-analysis on the primary outcome measures of amenorrhoea, heavy bleeding, and patients' dissatisfaction with treatment. <b>Data sources</b> Nineteen randomised controlled trials (involving 3287 women) were identified through electronic searches of the Cochrane Library, Medline, Embase and PsycINFO databases from inception to April 2011. The reference lists of known relevant articles were searched for further articles. Two reviewers independently selected articles without language restrictions. <b>Eligibility criteria for selecting studies</b> Randomised controlled trials involving second generation endometrial destruction techniques for women with heavy menstrual bleeding unresponsive to medical treatment. <b>Results</b> Of the three most commonly used techniques, network meta-analysis showed that bipolar radiofrequency and microwave ablation resulted in higher rates of amenorrhoea than thermal balloon ablation at around 12 months (odds ratio 2.51, 95% confidence interval 1.53 to 4.12, P&lt;0.001; and 1.66, 1.01 to 2.71, P=0.05, respectively), but there was no evidence of a convincing difference between the three techniques in the number of women dissatisfied with treatment or still experiencing heavy bleeding. Compared with bipolar radio frequency and microwave devices, an increased number of women still experienced heavy bleeding after free fluid ablation (2.19, 1.07 to 4.50, P=0.03; and 2.91, 1.23 to 6.88, P=0.02, respectively). Compared with radio frequency ablation, free fluid ablation was associated with reduced rates of amenorrhoea (0.36, 0.19 to 0.67, P=0.004) and increased rates of dissatisfaction (4.79, 1.07 to 21.5, P=0.04). Of the less commonly used devices, endometrial laser intrauterine thermotherapy was associated with increased rates of amenorrhoea compared with all the other devices, while cryoablation led to a reduced rate compared with bipolar radio frequency and microwave. <b>Conclusions</b> Bipolar radio frequency and microwave ablative devices are more effective than thermal balloon and free fluid ablation in the treatment of heavy menstrual bleeding with second generation endometrial ablation devices.
Dietary supplementation with a-linolenic acid decreases the levels of C-reactive protein, serum a amyloid, and interleukin-6 in dyslipidemic patients
Authors: Loukianos S. Rallidis, Georgios Paschos, Maria L. Papaloannou, Georgios K. Liakos, Aggeliki H. Velissaridou, Antonios Zampelas, Evangelos G. Papasteriadis
Journal: Journal of the American College of Cardiology (2003)