tbuckley/cabot-search huggingface dataset:
EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neuroectodermal tumor cells.
Authors: K Tanaka, T Iwakuma, K Harimaya, H Sato, Y Iwamoto
Journal: Journal of Clinical Investigation (1997)

The translocation t(11;22) is a common chromosomal abnormality detected both in Ewing's sarcoma and in primitive neuroectodermal tumor cells. The translocation results in an EWS-Fli1 fusion gene, made up of the 5' half of the EWS gene on chromosome 22 fused to the 3' half of the Fli1 gene on chromosome 11. Recent studies have evaluated possible roles of the fusion gene products. However, the biological significance of EWS-Fli1 is still unknown. Using a competitive polymerase chain reaction technique, we show here that there might be a correlation between the expression levels of the EWS-Fli1 fusion gene and the proliferative activities of Ewing's sarcoma and primitive neuroectodermal tumor cells. When the EWS-Fli1 expression is inhibited by antisense oligodeoxynucleotides against the fusion RNA, the growth of the tumor cells is significantly reduced both in vitro and in vivo. The data further indicate the growth inhibition of the cells by the antisense sequence might be mediated by G0/G1 block in the cell cycle progression. These results suggest that EWS-Fli1 may play an important role in the proliferation of the tumor cells, and the EWS-Fli1 fusion RNA could be used as a target to inhibit the growth of Ewing's sarcoma and primitive neuroectodermal tumor with the specific antisense oligonucleotide.
Bioequivalence of Levothyroxine Preparations for Treatment of Hypothyroidism
Authors: Melvin K. Spigelman
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Numerous published articles address the issue of levothyroxine bioequivalence. The conflicting results from these studies leave the closely related issues of bioequivalence and therapeutic interchange unresolved. This view is supported by treatment guidelines from leading thyroid societies as evidenced by their recommendation that patients switched from 1 levothyroxine preparation to another should be reevaluated, and if necessary retitrated.<sup>1,2</sup>Thus, the published guidelines of these societies recognize that the issue of levothyroxine bioequivalence has not been adequately addressed, and the question remains unanswered whether any 2 preparations provide similar levels of serum thyroxine (T<sub>4</sub>) and, accordingly, normalize serum thyrotropin (TSH) to the same degree. See also pp 1205 and 1238. In this context, Dr Dong and colleagues<sup>3</sup>assert their study shows that 4 levothyroxine preparations are bioequivalent. They should therefore be similarly effective and interchangeable in treating hypothyroidism, ie, normalizing TSH. However, the data of
A Clinical and Immunologic Evaluation of Women with Silicone Breast Implants and Symptoms of Rheumatic Disease
Authors: Alan J. Bridges
Journal: Annals of Internal Medicine (1993)

Objective: To describe the clinical and serologic features of women with silicone breast implants who were referred for symptoms of rheumatic disease. Design: A case series. Setting: University and private rheumatology practices. Patients: A total of 156 women with silicone breast implants and rheumatic disease complaints. Controls for the serologic studies included women with silicone implants and no rheumatic symptoms (n = 12) and women with fibromyalgia without silicone implants (n = 174). Measurements: Complete physical examination and testing for immunoglobulins; complement; C-reactive protein; rheumatoid factor; and autoantibodies by indirect immunofluorescence, immunodiffusion, and Western blot. Results: Three subgroups of patients were defined based on clinical and laboratory findings: joint and muscle pain (n = 95), joint swelling (n = 32), and connective tissue disease (n = 29). Most women had normal immunologic studies. The patients with joint swelling had mild, asymmetric, rheumatoid-factornegative synovitis that did not meet American College of Rheumatology criteria for rheumatoid arthritis. Fourteen patients had a scleroderma-like illness and anti-centromere or anti-PM-Scl antibodies by Western blot. Ten patients had a positive Western blot for BB polypeptide, a small nuclear ribonucleoprotein (snRNP), but did not meet criteria for systemic lupus erythematosus. No autoantibodies to known disease-related polypeptides were detected on Western blot in the control groups. Conclusion: Most women with silicone implants and rheumatic complaints had normal results of serologic tests and nonspecific symptoms, suggesting no serious connective tissue disease. However, a subset of women had clinical signs and serologic tests that were unusual even for referred patients. These observations suggest, but cannot establish, that some women with silicone breast implants may develop atypical immunologic reactions.
Physician-Computer Interaction as a Clinical Research Technique
Authors: Richard S. Cosby
Journal: JAMA (1971)

The technique of physician-computer interaction (PCI) herein described utilizes a clinical data bank for a single disease entity. Physician-computer interaction requires special programming so that the interrelationships of the various clinical and laboratory parameters may be immediately displayed. With use of a data bank composed of 60 variables in each of 500 patients with acute transmural myocardial infarction, the relationships of mortality to coronary care, age, serum glutamic oxabacetic transaminase level, white blood cell count, and congestive failure are illustrated. The technique of physician-computer interaction gives the clinician or researcher an enhanced diagnostic capability, unobtainable by batch processing or standard techniques of statistical analysis. In addition, there is greatly increased opportunity to relate variables in a number of ways. This technique further provides unusual capability in clinical care (individual physician and hospital staff), teaching (self-assessment program), clinical research (examining mortality), and administration.
SIMPLE METHOD OF INTRODUCING A MUSHROOM CATHETER
Authors: Nelse F. Ockerblad
Journal: JAMA (1923)

The mushroom catheter makes the ideal indwelling catheter. The usual introducers or obturators are not satisfactory in all cases. They work fairly well in a normal urethra, but in an exceptionally difficult, tortuous, prostatic urethra, they may fail. The method that I have used with much satisfaction is very simple. I once had occasion to introduce a mushroom catheter, but had no obturator with me. I had, however, a Walther ureteral bougie. I used the butt end of this, and slipped the catheter over it, and was successful in placing the catheter in the bladder. I used this on several occasions and found that it worked very well. Later, I encountered a tortuous prostatic urethra and found that the catheter would not make the turn. It then occurred to me that if I had some instrument that I could bend like a Coudé catheter, I could cause it to make
Immigration, parasitic infection, and United States religiosity
Authors: Jaimie N. Wall, Todd K. Shackelford
Journal: Behavioral and Brain Sciences (2012)

Abstract Fincher &amp; Thornhill (F&amp;T) present a powerful case for the relationship between parasite-stress and religiosity. We argue, however, that the United States may be more religious than can be accounted for by parasite-stress. This greater religiosity might be attributable to greater sensitivity to immigration, which may hyperactivate evolved mechanisms that motivate avoidance of potential carriers of novel parasites.
Alpha phenyl-tert-butyl nitrone (PBN) protects syngeneic marrow transplant recipients from the lethal cytokine syndrome occurring after agonistic CD40 antibody administration
Authors: Maria Gendelman, Nadine Halligan, Richard Komorowski, Brent Logan, William J. Murphy, Bruce R. Blazar, Kirkwood A. Pritchard, William R. Drobyski
Journal: Blood (2004)
Sexual revolution and sperm count
Authors: H J Menger
Journal: BMJ (1994)

EDITOR, - Together with other discoveries, the findings of Carlsen et al that the quality of semen has been declining over the past 50 years1 have led to disturbing speculation about the world's environment. I think, however, that the relation of their findings to such speculation is scientifically untenable.

Given the criteria for semen quality used by Carlsen et al, the findings suggest merely a general dilution of semen caused by more frequent ejaculation of men today compared with 50 years ago. But their conclusion …
Endothelial sulfonylurea receptor 1–regulated NCCa-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury
Authors: J. Marc Simard, Orest Tsymbalyuk, Alexander Ivanov, Svetlana Ivanova, Sergei Bhatta, Zhihua Geng, S. Kyoon Woo, Volodymyr Gerzanich
Journal: Journal of Clinical Investigation (2007)

Acute spinal cord injury (SCI) causes progressive hemorrhagic necrosis (PHN), a poorly understood pathological process characterized by hemorrhage and necrosis that leads to devastating loss of spinal cord tissue, cystic cavitation of the cord, and debilitating neurological dysfunction. Using a rodent model of severe cervical SCI, we tested the hypothesis that sulfonylurea receptor 1-regulated (SUR1-regulated) Ca(2+)-activated, [ATP](i)-sensitive nonspecific cation (NC(Ca-ATP)) channels are involved in PHN. In control rats, SCI caused a progressively expansive lesion with fragmentation of capillaries, hemorrhage that doubled in volume over 12 hours, tissue necrosis, and severe neurological dysfunction. SUR1 expression was upregulated in capillaries and neurons surrounding necrotic lesions. Patch clamp of cultured endothelial cells exposed to hypoxia showed that upregulation of SUR1 was associated with expression of functional SUR1-regulated NC(Ca-ATP) channels. Following SCI, block of SUR1 by glibenclamide or repaglinide or suppression of Abcc8, which encodes for SUR1 by phosphorothioated antisense oligodeoxynucleotide essentially eliminated capillary fragmentation and progressive accumulation of blood, was associated with significant sparing of white matter tracts and a 3-fold reduction in lesion volume, and resulted in marked neurobehavioral functional improvement compared with controls. We conclude that SUR1-regulated NC(Ca-ATP) channels in capillary endothelium are critical to development of PHN and constitute a major target for therapy in SCI.
Review: In acute respiratory failure, prehospital CPAP reduces mortality and intubation rates
Authors: Ayan Sen
Journal: Annals of Internal Medicine (2015)

Source Citation Goodacre S, Stevens JW, Pandor A, et al. Prehospital noninvasive ventilation for acute respiratory failure: systematic review, network meta-analysis, and individual patient data meta-analysis. Acad Emerg Med. 2014;21:960-70. 25269576
Bile acids and cytokines inhibit the human cholesterol 7α-hydroxylase gene via the JNK/c-jun pathway in human liver cells
Authors: Tiangang Li, Asmeen Jahan, John Y. L. Chiang
Journal: Hepatology (2006)

Cholesterol 7 alpha-hydroxylase (CYP7A1) of the bile acid biosynthesis pathway is suppressed by bile acids and inflammatory cytokines. Bile acids are known to induce inflammatory cytokines to activate the mitogen-activated protein kinase/c-Jun N-terminal kinase (JNK) signaling pathway that inhibits CYP7A1 gene transcription. c-Jun has been postulated to mediate bile acid inhibition of CYP7A1. However, the c-Jun target involved in the regulation of CYP7A1 is unknown. Human primary hepatocytes and HepG2 cells were used as models to study chenodeoxycholic acid (CDCA) and interleukin-1 beta (IL-1 beta) regulation of human CYP7A1 gene expression via real-time polymerase chain reaction, reporter assays, co-immunoprecipitation and chromatin immunocipitation (ChIP) assays. IL-1 beta and CDCA reduced CYP7A1 but induced c-Jun messenger RNA expression in human primary hepatocytes. IL-1beta inhibited human CYP7A1 reporter activity via the HNF4 alpha binding site. A JNK-specific inhibitor blocked the inhibitory effect of IL-1 beta on HNF4 alpha expression and CYP7A1 reporter activity. c-Jun inhibited HNF4 alpha and PPARgamma coactivator-1 alpha (PGC-1 alpha) coactivation of CYP7A1 reporter activity, whereas a dominant negative c-Jun did not. Co-immunoprecipitation and ChIP assays revealed that IL-1 beta and CDCA reduced HNF4 alpha bound to the CYP7A1 chromatin, and that c-Jun interacted with HNF4 alpha and blocked HNF4 alpha recruitment of PGC-1 alpha to the CYP7A1 chromatin. In conclusion, IL-1 beta and CDCA inhibit HNF4 alpha but induce c-Jun, which in turn blocks HNF 4 alpha recruitment of PGC-1 alpha to the CYP7A1 chromatin and results in inhibition of CYP7A1 gene transcription. The JNK/c-Jun signaling pathway inhibits bile acid synthesis and protects hepatocytes against the toxic effect of inflammatory agents.
Expression of IL-21 receptor in synovial tissue and blood of patients with rheumatoid arthritis
Authors: Marina Frleta, Vicky King, James H Reilly, Shauna Kerr, Derek S Gilchrist, Ditte Tornehave, Dorthe Lundsgaard, Ashley M Miller, Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> Cytokines regulate a broad range of inflammatory pathways in the pathogenesis of Rheumatoid Arthritis (RA), and cytokine blockade against tumour necrosis factor α and IL-6 has offered substantial advances in the treatment of articular inflammation. However, a large proportion of patients will not respond or exhibit only a partial response to treatment and new therapies are thus required. IL-21 is a member of the four-α-helix bundle family of cytokines that mediates pleiotropic effects through the IL-21 receptor (IL-21R). Since potency of IL-21 is mainly dependent on presence and abundance of its receptor on different cells types, the objective of this study was to characterise expression of IL-21R in the synovium and blood of patients with RA. <h3>Materials and methods</h3> Immunohistochemistry for IL-21R was carried out on synovial tissue samples derived by arthroplasty from patients with RA (n=5) obtained from the Institute of Infection, Immunity and Inflammation Research Tissue Bank. Mononuclear cells were separated out from peripheral blood (PBMC) of 10 RA patients or 3 healthy controls on a density gradient using Histopaque (Sigma) and analysed by flow cytometry for IL-21R expression on T cells (CD3/CD4/CD8), B cells (CD19/CD27) and NK cells (CD16/CD56). <h3>Results</h3> Expression of IL-21R was detected in 5/5 synovial RA tissues. The IL-21R<sup>+</sup> cells were located in the synovial intimal and sublining layers and in lymphoid aggregates. Flow cytometric analysis on blood PBMC revealed that IL-21R is highly expressed on both CD4<sup>+</sup> (73.04%, 12.58 MFI) and CD8<sup>+</sup> (50.88%, 13.69 MFI) T cells, as well as on a proportion of NK cells (73.83%, 19.15 MFI) in RA patients. On B cells, IL-21R expression was higher on the CD27<sup>-</sup> fraction of naïve B cells (95.19%, 37.02 MFI), with lower expression on the CD27<sup>+</sup> memory B cells (15.2%, 32.22 MFI). <h3>Conclusions</h3> Our results show increased expression of IL-21R in established RA synovial tissue and peripheral blood, and indicate that targeting of the IL-21/IL-21R pathway may be a valid therapeutic strategy for the treatment of RA.
Walter Henry — A Very Lilyputian Hero
Authors: Charles G. Roland
Journal: New England Journal of Medicine (1969)

IN the preface of his two-volume autobiography, Trifles from my Port-Folio,1 Dr. Walter Henry labels himself "Lilyputian." It is true that he made no scientific discoveries. Without his autobiography, Henry's name would have vanished, or at most, might be cited as that of one physician on St. Helena when Napoleon died. Nevertheless, Henry is worth remembering (Fig. 1). He is the archetypical wandering Irishman, charming, witty and intelligent, with an eye for the ladies and an adventurous nature.From his birth in Donegal in 1791 till his death in Ontario, Canada, 69 years later, he passed from one adventurous . . .
A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus
Authors: David M. Treiman, Patti D. Meyers, Nancy Y. Walton, Joseph F. Collins, Cindy Colling, A. James Rowan, Adrian Handforth, Edward Faught, Vincent P. Calabrese, Basim M. Uthman, R. Eugene Ramsay, Meenal B. Mamdani, Pratap Yagnik, John C. Jones, Elizabeth Barry, Jane G. Boggs, Andres M. Kanner
Journal: New England Journal of Medicine (1998)

Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled.
Doctors worried about threat to supplies of animal insulin
Authors: M. Hunter
Journal: BMJ (2002)

Fears that worldwide production of animal insulin could be put at risk by the proposed takeover of Brazilian manufacturer Biobras have been dismissed by the multinational pharmaceutical company involved in the buy-out.

Novo Nordisk has “no plans for the discontinuation of production of animal insulin.” Nor will it halt Biobras's supply of source material to other companies that manufacture insulin, claimed Novo's executive vice president, Lars Jorgensen.

Concerns over the bid, which has been accepted by the Biobras board and is currently under …
Art Injection: Youth Arts in Hospital
Authors: D Isaacs
Journal: BMJ (1994)

Ed Amanda Buckland Available from Child Health information Unit, Royal Alexandra Hospital for Children, Camperdown NSW 2050, Australia (A$25, pp 72) ISBN 0–9599152–7–3

To be an adolescent is to be disadvantaged, caught in a limbo between the child and adult worlds, misunderstood by almost everyone. To be a chronically ill adolescent is a double disadvantage.

Adolescents often find it difficult to cope with their feelings and have difficulty communicating their problems. Art is one medium through which adolescents can express their feelings, a medium that they do not find threatening; and the act of creativity can itself be therapeutic. Art Injection provides a detailed and practical account of how one hospital's youth art programme has developed.

The department of adolescent …
TRβ is the critical thyroid hormone receptor isoform in T3-induced proliferation of hepatocytes and pancreatic acinar cells
Authors: Marta A. Kowalik, Andrea Perra, Monica Pibiri, Maria T. Cocco, Jacques Samarut, Michelina Plateroti, Giovanna M. Ledda-Columbano, Amedeo Columbano
Journal: Journal of Hepatology (2010)
Prognostic value of nonlinear heart rate dynamics in hemodialysis patients with coronary artery disease
Authors: Hidekatsu Fukuta, Junichiro Hayano, Shinji Ishihara, Seiichiro Sakata, Nobuyuki Ohte, Hiroshi Takahashi, Masaki Yokoya, Takanobu Toriyama, Hirohisa Kawahara, Kazuhiro Yajima, Kenji Kobayashi, Genjiro Kimura
Journal: Kidney International (2003)
EVALUATION OF 134 CONSECUTIVE PATIENTS FOR THE PRESENCE OF SIGNIFICANT CORONARY ARTERY DISEASE (CAD) WITH A SINGLE HEADED SPECT GAMMA CAMERA WITH DUAL ISOTOPE IMAGING.
Authors: R. C. Walker
Journal: Clinical Nuclear Medicine (1997)

Radiology Consultants of Little Rock, J. Y. Dollar, R. Parkhurst, and J. B. Calkins, Central Arkansas Cardiology, North Little Rock, AR
Abstract 1444: Weighted Gene Co-expression Network Analysis of Adipose and Liver Reveals Gene Modules Related to Plasma HDL Levels and Containing Candidate Genes at Loci Identified in Genome Wide Association Studies
Authors: Peter Langfelder, Margarete Mehrabian, Eric E Schadt, Aldons J Lusis, Steve Horvath
Journal: Circulation (2008)

The genetic and environmental factors contributing to HDL-cholesterol levels are highly complex. For example, a recent meta-analysis of three genome wide association studies (GWAS), consisting of over 9000 individuals, revealed several loci, but altogether these explained less than 10% of HDL variation. Since HDL has a heritability of about 50%, there clearly must be many as yet unidentified factors. To better address this complexity, we have utilized integrative genomic approaches to relate common DNA variation to gene networks and HDL metabolism. We report a Weighted Gene Co-expression Network Analysis (WGCNA) of genome-wide expression data from a CAST X C57BL6/J F2 intercross. WGCNA is a systems-based gene expression analysis and gene screening method. It utilizes co-expression patterns among genes to identify gene modules (groups of highly co-expressed genes) significantly associated with a clinical trait, in this case plasma HDL levels. Co-expression modules may represent cellular processes and interacting pathways that provide a bridge between individual genes and a systems-level view of the organism. A module-centric analysis effectively alleviates the multiple testing problems inherent in microarray data analysis and can be considered a biologically motivated data-reduction scheme. Using data from liver and adipose tissues, we have identified several modules strongly associated with plasma HDL levels (p-values ranging from below 1e-20 to 1e-5). Gene ontology and functional enrichment analysis indicate that these modules are indeed biologically meaningful. The modules contain variants of several genes under loci that were recently implicated by three GWA studies: liver modules include GCKR, ANGPTL4, ABCA3, APOA1, and APOA4, while the adipose modules include ABCA6, ANGPTL11 and 12, MMAB, MLXIPL, SORT1, PBX4, PLTP, and APOL6. Thus, our study also serves to help identify likely candidates from GWAS. In conclusion, applying WGCNA methods reveals modules that are biologically meaningful, statistically significant, and enriched for genes and pathways related to HDL metabolism and transport.