tbuckley/cabot-search huggingface dataset:
Attenuation of the Slow Component of Delayed Rectification, Action Potential Prolongation, and Triggered Activity in Mice Expressing a Dominant-Negative Kv2 α Subunit
Authors: Haodong Xu, Dianne M. Barry, Huilin Li, Sylvain Brunet, Weinong Guo, Jeanne M. Nerbonne
Journal: Circulation Research (1999)

Abstract —An in vivo experimental strategy, involving cardiac-specific expression of a mutant Kv 2.1 subunit that functions as a dominant negative, was exploited in studies focused on exploring the role of members of the Kv2 subfamily of pore-forming (α) subunits in the generation of functional voltage-gated K + channels in the mammalian heart. A mutant Kv2.1 α subunit (Kv2.1N216) was designed to produce a truncated protein containing the intracellular N terminus, the S1 membrane–spanning domain, and a portion of the S1/S2 loop. The truncated Kv2.1N216 was epitope tagged at the C terminus with the 8–amino acid FLAG peptide to generate Kv2.1N216FLAG. No ionic currents are detected on expression of Kv2.1N216FLAG in HEK-293 cells, although coexpression of this construct with wild-type Kv2.1 markedly reduced the amplitudes of Kv2.1-induced currents. Using the α-myosin heavy chain promoter to direct cardiac specific expression of the transgene, 2 lines of Kv2.1N216FLAG-expressing transgenic mice were generated. Electrophysiological recordings from ventricular myocytes isolated from these animals revealed that I K, slow is selectively reduced. The attenuation of I K, slow is accompanied by marked action potential prolongation, and, occasionally, spontaneous triggered activity (apparently induced by early afterdepolarizations) is observed. The time constant of inactivation of I K, slow in Kv2.1N216FLAG-expressing cells (mean±SEM=830±103 ms; n=17) is accelerated compared with the time constant of I K, slow inactivation (mean±SEM=1147±57 ms; n=25) in nontransgenic cells. In addition, unlike I K, slow in wild-type cells, the component of I K, slow remaining in the Kv2.1N216FLAG-expressing cells is insensitive to 25 mmol/L tetraethylammonium. Taken together, these observations suggest that there are 2 distinct components of I K, slow in mouse ventricular myocytes and that Kv2 α subunits underlie the more slowly inactivating, tetraethylammonium-sensitive component of I K, slow . In vivo telemetric recordings also reveal marked QT prolongation, consistent with a defect in ventricular repolarization, in Kv2.1N216FLAG-expressing transgenic mice.
173. Novel Cell-Specific Gene Delivery for Tumors Using a Drug or Gene Delivery System Based on Responses to Intracellular Signals (D-RECS) Concept
Authors: Yoshiki Katayama, Jeong Hun Kang, Daisuke Asai, Takeshi Mori, Takuro Niidome
Journal: Molecular Therapy (2006)

Gene therapy has been anticipated as a medical approach for treating tumors or hereditary diseases. However, there is a serious issue regarding the present gene delivery methodologies, since almost all the gene delivery methods have insufficient ability to specifically recognize the target diseased cells and distinguish them from normal cells, especially in the same tissue or organ. Here, we propose a novel method for gene therapy using our recently proposed concept of a drug or gene delivery system based on responses to cellular signals (D-RECS) (1,2), particularly to phosphorylation of protein kinase C (PKC) α. In this concept, an intracellular signal that is specifically and abnormally activated in the target diseased cells is used for the activation of transgene expression. We tried here to apply our D-RECS concept for cancer treatment using PKCa as a target signal. PKC α is a serine/threonine kinase that plays key roles in tumor cell differentiation and proliferation. Thus, a cationic peptide that was highly sensitive to PKC α was designed and a polyacrylamide polymer containing this peptide as pendant side chains was synthesized. The polymer containing the cationic peptide formed a stable complex with anionic DNA, which suppressed gene expression. When the peptide was phosphorylated by PKC α, the DNA was released from the polymer-DNA complex, indicating that the newly developed polymer was suitable for tumor cell-specific control of gene expression in a target tissue. Intratumor delivery of a luciferase-encoding plasmid DNA using the polymer was performed by electroporation. The luciferase activity in the delivery system using the positive polymer for PKC α phosphorylation was over 20-fold higher than that using a negative control polymer in which the phosphorylated serine in the peptide was substituted with alanine. These results indicate that the D-RECS method is applicable to gene therapy in vivo. In addition, our method will make it possible to differentially control transgene expression in normal and abnormal cells by controlling the phosphorylation sensitivity and selectivity of the substrate peptide to a target molecule showing extraordinary and continuous activation in the target diseased cells. References: 1) J. Oishi, K. Kawamura, J-H. Kang, K. Kodama, T. Sonoda, M. Murata, T. Niidome, Y. Katayama, J. Control. Release110, 431–436, 2006 2) K. Kawamura, J. Oishi, J-H. Kang, K. Kodama, T. Sonoda, M. Murata, T. Niidome, Y. Katayama, Biomacromolecules.6, 908–913, 2005.
Fetal Perspective of Rubella Vaccine Efficacy and Safety
Authors: John P. Fox
Journal: JAMA (1981)

Licensure of a new vaccine requires a judgment concerning efficacy and safety that, in most cases, have been demonstrated by "clinical" trials conducted in previously nonimmune volunteers. Evidence for efficacy is provided by demonstration of relevant antibody response by a high proportion (at least 95%) of vacinees and of significant protection against challenge (disease or infection prevented). Observations as to the frequency and nature of adverse effects induced in vaccine recipients constitute the evidence relating to safety. The point is not how efficacy and safety are defined but that the relevant evidence for both ordinarily comes from direct observation of the persons who receive the vaccine. Rubella vaccine differs from other vaccines in that the principal intended beneficiaries will be fetuses not yet conceived. Thus, while it was necessary that efficacy and safety for vaccinees be demonstrated (and they have been), much more evidence is required before well-founded judgments can
Performance of United States Citizens with Foreign Medical Education on Standardized Medical Examinations
Authors: Ethel Weinberg, Anita I. Bell
Journal: New England Journal of Medicine (1978)

To enter the mainstream of American medicine, United States students who enroll in foreign medical schools must either transfer to a United States medical school (usually after passing Part I of the NMBE examination) or complete their studies abroad and then pass FLEX and usually ECFMG examinations. Half those applying for transfer fail Part I. Although virtually all who succeed in transferring subsequently pass Parts II and III, their scores are below the mean of the reference group, and their relative performance progressively deteriorates. Sixty per cent of USFMG's fail the medical portion of the ECFMG examination as compared to an expected failure rate for United States medical students of only 2 to 3 per cent. Thirty-eight per cent of USFMG's who take both ECFMG and FLEX examinations fail the latter. The mean weighted score for USFMG's on FLEX is 75.8, while that for United States graduates is 80.1 and for FMG's 74.7. These preliminary data suggest that United States students who go abroad, regardless of where they complete their studies, do not perform as well on standard tests after they return home as do those who have had their entire education in United States schools. This question needs more systematic study.
US doctors file lawsuit against antiabortionists
Authors: F. Charatan
Journal: BMJ (1999)

In Oregon, Planned Parenthood and a group of physicians who perform abortions have filed a civil suit against several anti-abortion groups individuals. The suit seeks $200 million in damages and an injunction to bar the defendants from posting information on the Internet that threatens the lives and well-being of the plaintiffs. One such anti-abortion World Wide Web site targets 225 physicians who provide abortions.
Single-Dose Penicillin Prophylaxis against Neonatal Group B Streptococcal Infections
Authors: Jane D. Siegel, George H. McCracken, Norma Threlkeld, Bonnie Milvenan, Charles R. Rosenfeld
Journal: New England Journal of Medicine (1980)

Neonatal Group B streptococcal infections may not respond to antimicrobial therapy and have been associated with case fatality rates of 50 per cent or greater. We evaluated the effect on colonization and disease rates of a single intramuscular dose of aqueous penicillin G given at birth in a prospectively controlled study of 18,738 neonates during a 25-month period. The colonization rate in the mothers was 26.6 per cent, with 50 per cent concordance in the untreated infants and 12.2 per cent in the penicillin-treated infants (P<0.001). There was a significant decrease in the incidence of disease caused by all penicillin-susceptible organisms in the penicillin group (0.64 vs. 2.26 cases per thousand live births, P=0.005). Disease caused by penicillin-resistant pathogens was increased in the penicillin-treated group during the first year of the study but was unaffected during the second year. Routine administration of parenteral penicillin at birth cannot be recommended until the effect on the incidence of disease caused by penicillin-resistant pathogens is fully defined. (N Engl J Med. 1980; 303:769–75.)
Intragenic Recombination Events and Evidence for Hybrid Speciation in Nicotiana (Solanaceae)
Authors: Laura J. Kelly, Andrew R. Leitch, James J. Clarkson, Robin B. Hunter, Sandra Knapp, Mark W. Chase
Journal: Molecular Biology and Evolution (2009)

Reticulate evolution may function both at the species level, through homoploid and polyploid hybridization, and below the species level, through inter and intragenic recombination. These processes represent challenges for the reconstruction of evolutionary relationships between species, because they cannot be represented adequately with bifurcating trees. We use data from low-copy nuclear genes to evaluate long-standing hypotheses of homoploid (interspecific) hybrid speciation in Nicotiana (Solanaceae) and reconstruct a complex series of reticulation events that have been important in the evolutionary history of this genus. Hybrid origins for three diploid species (Nicotiana glauca, N. linearis, and N. spegazzinii) are inferred on the basis of gene tree incongruence, evidence for interallelic recombination between likely parental alleles, and support for incompatible splits in Lento plots. Phylogenetic analysis of recombinant gene sequences illustrates that recombinants may be resolved with one of their progenitor lineages with a high posterior probability under Bayesian inference, and thus there is no indication of the conflict between phylogenetic signals that results from reticulation. Our results illustrate the importance of hybridization in shaping evolution in Nicotiana and also show that intragenic recombination may be relatively common. This finding demonstrates that it is important to investigate the possibility of recombination when aiming to detect hybrids from DNA-sequence data and reconstruct patterns of reticulate evolution between species.
Penicillin Treatment of Streptococcal Pharyngitis
Authors: Phillip I. Nieburg
Journal: JAMA (1973)

<h3>To the Editor.—</h3> The recent report by Colcher and Bass illustrates the positive effect of parental counseling in the treatment of streptococcal pharyngitis with orally administered penicillin. It will serve to reinforce the efforts of those of us who give written instructions and explanations to parents whose children are receiving various treatment regimens. However, the final sentence in the article, favorably comparing oral with parenteral therapy, may be misleading and does not appear justified by the data. All children treated intramuscularly were given 1.2 million units of a mixture of penicillin G procaine and penicillin G benzathine (Bicillin C-R), containing 600,000 units of the latter. As stated in the "Red Book,"<sup>2</sup>the recommended dose for children weighing more than 27.1 kg (60 lb) is 900,000 to 1,200,000 units. The Red Book further states "mixtures containing shorter-acting penicillins in addition to penicillin G benzathine have not been shown to be
Development of healthcare quality indicators for rheumatoid arthritis in Europe: the eumusc.net project
Authors: Ingemar F Petersson, Britta Strömbeck, Lene Andersen, Marco Cimmino, Rolf Greiff, Estibaliz Loza, Carlo Sciré, Tanja Stamm, Michaela Stoffer, Till Uhlig, Anthony D Woolf, Theodora P M Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2013)

Eumusc.net (http://www.eumusc.net) is a European project supported by the EU and European League Against Rheumatism to improve musculoskeletal care in Europe.To develop patient-centred healthcare quality indicators (HCQIs) for healthcare provision for rheumatoid arthritis (RA) patients.Based on a systematic literature search, existing HCQIs for RA were identified and their contents analysed and categorised referring to a list of 16 standards of care developed within the eumusc.net. An international expert panel comprising 14 healthcare providers and two patient representatives added topics and during repeated Delphi processes by email ranked the topics and rephrased suggested HCQIs with the preliminary set being established during a second expert group meeting. After an audit process by rheumatology units (including academic centres) in six countries (The Netherlands, Norway, Romania, Italy, Austria and Sweden), a final version of the HCQIs was established.56 possible topics for HCQIs were processed resulting in a final set of HCQIs for RA (n=14) including two for structure (patient information and calculation of composite scores), 11 for process (eg, access to care, assessments, and pharmacological and non-pharmacological treatments) and one for outcome (effect of treatment on disease activity). They included definitions to be used in clinical practice and also by patients. Further, the numerators and the denominators for each HCQI were defined.A set of 14 patient-centred HCQIs for RA was developed to be used in quality improvement and bench marking in countries across Europe.
Ophthalmic Disease and the Pill
Authors: J. C. McGrand, C. C. Cory
Journal: BMJ (1969)

Based on various reports it is suspected that oral contraceptives produce ocular side-effects.  A case is reported of a 29-year-old woman who presented with a persisting black shadow in the lower part of the right visual field and was admitted to the Royal Eye Medical Ophthalmological Unit.  She had been taking megestrol acetate (Volidan) tablets for 4 years and had increased the dose to 2 tablets daily because of breakthrough bleeding 5 months prior to this incident.  Examination of the right fundus showed an occlusion of the superotemporal arteriole with a corresponding field defect and a visual acuity of 6/6 part.  Full investigation revealed no abnormality and presently her right vision is 6/6 and the visual defect unchanged.  The upper temporal arteriole is narrowed with sheathing and there is temporal pallor of the disc.  Since this patient had no clinical or radiological evidence of an extracerebral source of the embolus to account for her retinal artery occlusion and since some thromboembolic and cerebrovascular disorders and side-effects are suspected  linked with oral contraceptives it is hypothesized that the megestrol taken here might be an important factor in the ocular defect.  Other patients on orals have also reported with ocular disease; these authors believe that further clinical trails are warranted to determine the true incidence of ocular side-effects with oral contraceptives.
Interleukin 4 increases human synovial cell expression of VCAM-1 and T cell binding.
Authors: H Shimada, K Eguchi, Y Ueki, M Nakashima, I Yamashita, Y Kawabe, M Sakai, H Ida, T Aoyagi, S Nagataki
Journal: Annals of the Rheumatic Diseases (1994)

The effects were studied of interleukin 4 (IL-4) on T cell-synovial cell adhesion and on the expression of adhesion molecules on the surface of synovial fibroblast-like cells. The adhesion of T cells toward the synovial cells were measured by 51chromium-labelled adhesion assay. The expression of adhesion molecules on synovial cells were analysed by flowcytometry. Stimulation of synovial cells with IL-4 increased T cell-synovial cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VCAM-1 on the surface of synovial cells, but not the expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on the expression of ICAM-1 or VCAM-1 on the surface of synovial cells. The increased adhesion of T cells to IL-4 stimulated synovial cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti-VCAM-1 antibodies blocked completely T-cell binding to IL-4 stimulated synovial cells. These results suggest that the increased adhesion of T cells to IL-4-stimulated synovial cells is mediated by VLA-4/VCAM-1 pathway.
Prise en charge endoscopique des fistules post »Sleeve« gastrectomie: l'expérience montpelliéraine
Authors: JC Valats, P Bauret, M Skallzi, J Domergue, JM Fabre, D Nocca
Journal: Endoscopy (2010)

Introduction: La »Sleeve« Gastrectomie sous Laparoscopie« (LSG) est une technique récemment validée par l' HAS (2008) dans le traitement chirurgical des patients avec obésité morbide. Sa morbidité est évaluée entre 0,5 et 7% en fonction des séries. La survenue d'une fuite sur la ligne d'agrafage est la principale complication, potentiellement létale. Nous rapportons l'expérience de notre centre dans la prise en charge endoscopique de cette complication.
Reply to Matsushita et al.
Authors: S. Jutaghokiat, P. Angsuwatcharakon, B. Imraporn, R. Rerknimitr
Journal: Endoscopy (2009)

We thoroughly understand the comment by Matsushita et al., regarding our case, that EGD is a risky procedure in a patient with possible aortic dissection. However, we still believe that EGD is crucial for identifying the cause of bleeding since not all bleeding can be assumed to result from mesenteric infarction; mesenteric ischemia has been found in fewer than ⅕ of cases in an aortic dissection with bleeding series [1]. On the other hand, multidetector CT angiography is not always a harmless investigation, since a significant number of aortic dissection cases have the risk of acute renal failure [2], and the contrast that is used for the study may precipitate worsening of renal function. Although both CT angiography and EGD have significant risks, nevertheless we agree that both are essential for the diagnosis of acute aortic dissection with intestinal bleeding. Though the sequence of the two is debatable, we would like to emphasize that optimal preparation including adequate control in blood pressure and volume are needed prior to both tests. In our patient, before he underwent EGD, the blood pressure was properly managed and we limited the amount of air insufflation in this quick diagnostic run.
Prospective Study of a Pirarubicin, Intermediate-Dose Cytarabine, and Etoposide Regimen in Children With Down Syndrome and Acute Myeloid Leukemia: The Japanese Childhood AML Cooperative Study Group
Authors: Kazuko Kudo, Seiji Kojima, Ken Tabuchi, Hiromasa Yabe, Akio Tawa, Masue Imaizumi, Ryoji Hanada, Kazuko Hamamoto, Ryoji Kobayashi, Akira Morimoto, Hideki Nakayama, Masahiro Tsuchida, Keizo Horibe, Hisato Kigasawa, Ichiro Tsukimoto
Journal: Journal of Clinical Oncology (2007)

Purpose To evaluate a less intensive chemotherapeutic regimen specifically designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML), and to determine the prognostic factors for event-free survival. Patients and Methods Seventy-two patients with AML-DS were treated with remission induction chemotherapy consisting of pirarubicin (25 mg/m 2 /d for 2 days), cytarabine (100 mg/m 2 /d for 7 days), and etoposide (150 mg/m 2 /d for 3 days). Patients received four courses of intensification therapy of the same regimen. Prophylaxis for CNS leukemia was not included. Results All but two patients were younger than 4 years, and 67 of the 72 patients (93%) were diagnosed as acute megakaryoblastic leukemia (AMKL). Seventy of the 72 patients (97.2%) achieved a complete remission (CR), and the estimated 4-year event-free survival (EFS) rate was 83% ± 9%. Nine patients relapsed, and one died as a result of pneumonia during CR. Multivariate analysis revealed that the presence of monosomy 7 was a greater risk factor of adverse outcome (odds ratio = 5.67; P = .027). Conclusion A less intensive chemotherapeutic regimen produces excellent outcomes in standard-risk AML-DS patient. Risk-oriented therapy should be considered for future trials in AML-DS.
Balancing Family and Career: Men Are in the Trenches, Too
Authors: Molly Carnes
Journal: Annals of Internal Medicine (1997)

Letters15 April 1997Balancing Family and Career: Men Are in the Trenches, TooMolly Carnes, MDMolly Carnes, MDUniversity of Wisconsin, Madison, WI 53705Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-8-199704150-00043 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:You sound like a wonderful husband. Welcome to the trenches and pass the channel changer! Author, Article, and Disclosure InformationAuthors: Molly Carnes, MDAffiliations: University of Wisconsin, Madison, WI 53705 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 April 1997Volume 126, Issue 8Page: 670 ePublished: 15 August 2000 Issue Published: 15 April 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A cluster of anaphylactic reactions in children with spina bifida during general anesthesia: Epidemiologic features, risk factors, and latex hypersensitivity
Authors: Kevin J. Kelly, Michell L. Pearson, Viswanath P. Kurup, Peter L. Havens, Robert S. Byrd, Mary A. Setlock, Jay C. Butler, Jay E. Slater, Leslie C. Grammer, Abraham Resnick, Mary Roberts, William R. Jarvis, Jeffrey P. Davis, Jordan N. Fink
Journal: Journal of Allergy and Clinical Immunology (1994)
CIVIL HOSPITAL TRAINING FOR MEN OF THE R.A.M.C.(VOL.): A SUGGESTION
Authors: W. Sheen
Journal: BMJ (1906)

IN order that the men of the volunteer branch of the Royal Army Medical Corps may perform their duties -efficiently, it is necessary that they receive training as .sicknurses as well as in bearer company work.The only opportunity which at present they have for the former training is the annual camp of a week's duration.The -cases are few and slight in character, and the time is quite
The Bench Press Mark
Authors: ERIC S. GRIMM, CARLOS BEKERMAN
Journal: Clinical Nuclear Medicine (1992)

Abnormal muscle uptake in multiple sites following strenuous exercise has been extensively reported. Muscle localization of bone agents has also been described in conditions associated with muscle damage such as myositis ossificans, polymyositis, rhabdomyolysis, and trauma. Muscle damage from strenuous exercise causes disruption of muscle cells with an influx of calcium into the damaged cell. The bone-seeking agent then localizes to intracellular calcium, amorphous calcium phosphate, and crystalline hydroxyapatite. Other mechanisms of uptake by damaged skeletal muscle may include hyperemia, adsorption onto soft-tissue calcium and immature collagen, and binding to tissue receptors and denatured proteins. Though many explanations have been postulated, the exact mechanism of the localization of boneseeking agents in injured skeletal muscle remains unclear.