tbuckley/cabot-search huggingface dataset:
1124. Correction of Glycogen Storage Disease Type II by an AAV Vector Encoding Highly-Secreted, Chimeric Acid α-glucosidase
Authors: Baodong Sun, Talmage Brown, Andrew Bird, Ayn Schneider, Sarah P. Young, Alison McVie-Wylie, Y.-T. Chen, Dwight D. Koeberl
Journal: Molecular Therapy (2005)

Top of pageAbstract
GSD-II (Pompe disease; MIM 232300) is an autosomal recessive disorder caused by the deficiency in the activity of the lysosomal enzyme acid |[alpha]|-glucosidase (GAA; acid maltase; EC 3.2.1.20). The disease is characterized by the massive accumulation of glycogen in lysosomes and in the cytoplasm of striated muscle, with an accompanying disruption of cellular functions. The efficacy of therapy with lysosomal enzymes, such as GAA, could be markedly improved if secretion of these proteins from producer cells were increased. Secreted proteins are directed extracellularly by the presence of an N-terminal signal peptide. We have investigated the hypothesis that a chimeric lysosomal enzyme containing an alternative signal peptide will achieve much higher secretion of the recombinant lysosomal enzyme from transduced cells. The coding sequence of human GAA was modified by substituting alternative signal peptides from highly secreted proteins for the native GAA signal peptide (denoted chimeric GAA). The relative secretion of chimeric GAA from transfected 293 cells increased up to 26-fold, compared to the secretion of unmodified GAA. The efficacy of this strategy for gene therapy in Pompe disease was analyzed in GAA-knockout (GAA-KO) mice. An adeno-associated virus (AAV) vector containing a liver-specific promoter to drive the expression of GAA was constructed (AAV-LSPSPhGAApA) and pseudotyped as AAV8. The long-term efficacy of SP-hGAA was evaluated by the quantitation of GAA activity and glycogen content following AAV-LSPSPhGAApA administration. A dose-response analysis revealed sustained, high GAA activity in plasma following administration of at least 3 |[times]| 1010 particles; however, an equivalent number of particles for a vector encoding unmodified GAA did not elevate GAA activity in plasma. Receptor-mediated uptake of secreted GAA can be demonstrated only if plasma levels exceed a therapeutic threshold, and the GAA activity of the heart and diaphragm were significantly elevated 18 weeks following administration of as few as 1 |[times]| 1010 particles of AAV-LSPSPhGAApA. GAA activity in the quadriceps muscle was increased with as few as 3 |[times]| 1010 particles of AAV-LSPSPhGAApA. The lower threshold for significant reduction of heart, diaphragm, and quadriceps glycogen content with AAV-LSPSPhGAApA was 3 |[times]| 1010 particles. Neither fewer particles for that vector, nor an equivalent number of particles of the analogous vector encoding unmodified GAA affected glycogen content in the quadriceps. Thus, an AAV vector encoding chimeric GAA increased the secretion of hGAA from the liver, and reduced the number of vector particles required to achieve a therapeutic effect in GSD-II mice.
Congenital skin Bstula with sternal cleft
Authors: T. Miyamoto, Y. Hosoda, Y. Fujimoto, M. Fujishima, R. Sasaoka, M. Mihara
Journal: British Journal of Dermatology (1995)

Journal Article Congenital skin Bstula with sternal cleft Get access T. Miyamoto, T. Miyamoto Department of Dermatology, Central Hospital, Nikaimachi 67, Tsuyama 708, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Hosoda, Y. Hosoda Department of Paediatrics, Central Hospital, Nikaimachi 67, Tsuyama 708, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Fujimoto, Y. Fujimoto Department of Paediatrics, Central Hospital, Nikaimachi 67, Tsuyama 708, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Fujishima, M. Fujishima Department of Radiology, Central Hospital, Nikaimachi 67, Tsuyama 708, Japan Search for other works by this author on: Oxford Academic Google Scholar R. Sasaoka, R. Sasaoka Department of Dermatology, Faculty of Medicine, Tottori University, Nishimachi 36, Yonago 683, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Mihara M. Mihara Department of Dermatology, Faculty of Medicine, Tottori University, Nishimachi 36, Yonago 683, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 3, 1 March 1995, Pages 492–494, https://doi.org/10.1111/j.1365-2133.1995.tb08700.x Published: 01 March 1995
Drug-Eluting Stent Restenosis Rates?
Authors: Charles J. McKenna
Journal: Circulation (2004)

Drug-Eluting Stent Restenosis Rates?The article by Lemos et al 1 describing coronary restenosis after implantation of sirolimus-eluting stents is of great interest.With the increasing demand for drug-eluting stents (DES) and the recent formation of guidelines for their use, confirmation of their continued efficacy in reducing restenosis is important.Therefore, registry data from a large patient population such as the Thoraxcenter (Rotterdam, the Netherlands)-probably the largest DES patient population in the world-is greatly welcomed.The authors state that coronary angiography was performed at follow-up for two reasons, ie, if clinically indicated or for "complex" patients.The Results section describes 121 of the 192 patients with complex characteristics.Nineteen of these patients had restenosis, which, although not stated, translates into a restenosis rate of 19/121 (16%).The results make no mention of the patients who had coronary angiography performed for clinical reasons, ie, symptoms or positive ischemic tests.Some of the complex patients are presumably included in this group also.However, it would be most helpful to know the following.1.The total number of patients who have had a DES implanted.2. The number (%) of the above who represented with clinical evidence suggesting restenosis.3. The number (%) of these patients who underwent repeat angiography and had angiographic restenosis identified.This information, if available, would be clinically relevant and, hopefully, help all interventionists in their struggles to promote DES use.
Robo4 is an effective tumor endothelial marker for antibody-drug conjugates based on the rapid isolation of the anti-Robo4 cell-internalizing antibody
Authors: Mai Yoshikawa, Yohei Mukai, Yoshiaki Okada, Yuki Tsumori, Shin-ichi Tsunoda, Yasuo Tsutsumi, William C. Aird, Yasuo Yoshioka, Naoki Okada, Takefumi Doi, Shinsaku Nakagawa
Journal: Blood (2013)
miR-125b targets erythropoietin and its receptor and their expression correlates with metastatic potential and ERBB2/HER2 expression
Authors: Manuela Ferracin, Cristian Bassi, Massimo Pedriali, Sara Pagotto, Lucilla D’Abundo, Barbara Zagatti, Fabio Corrà, Gentian Musa, Elisa Callegari, Laura Lupini, Stefano Volpato, Patrizia Querzoli, Massimo Negrini
Journal: Molecular Cancer (2013)

The microRNA 125b is a double-faced gene expression regulator described both as a tumor suppressor gene (in solid tumors) and an oncogene (in hematologic malignancies). In human breast cancer, it is one of the most down-regulated miRNAs and is able to modulate ERBB2/3 expression. Here, we investigated its targets in breast cancer cell lines after miRNA-mimic transfection. We examined the interactions of the validated targets with ERBB2 oncogene and the correlation of miR-125b expression with clinical variables. MiR-125b possible targets were identified after transfecting a miRNA-mimic in MCF7 cell line and analyzing gene expression modifications with Agilent microarrays and Sylamer bioinformatic tool. Erythropoietin (EPO) and its receptor (EPOR) were validated as targets of miR-125b by luciferase assay and their expression was assessed by RT-qPCR in 42 breast cancers and 13 normal samples. The molecular talk between EPOR and ERBB2 transcripts, through miR-125b, was explored transfecting MDA-MD-453 and MDA-MB-157 with ERBB2 RNA and using RT-qPCR. We identified a panel of genes down-regulated after miR-125b transfection and putative targets of miR-125b. Among them, we validated erythropoietin (EPO) and its receptor (EPOR) - frequently overexpressed in breast cancer - as true targets of miR-125b. Moreover, we explored possible correlations with clinical variables and we found a down-regulation of miR-125b in metastatic breast cancers and a significant positive correlation between EPOR and ERBB2/HER2 levels, that are both targets of miR-125b and function as competing endogenous RNAs (ceRNAs). Taken together our results show a mechanism for EPO/EPOR and ERBB2 co-regulation in breast cancer and confirm the importance of miR-125b in controlling clinically-relevant cancer features.
Dosage is important when using oxygen for patients with myocardial infarction
Authors: Philip James, Vance Spence
Journal: Journal of the Royal Society of Medicine (2007)

In questioning the use of oxygen supplementation for patients with myocardial infarction, Beasley and colleagues1 failed to discuss the importance of the plasma tension and the relevant science (JRSM 2007;100:130-133). Cardiac output is tailored to oxygen demand and vascular tone relates to the plasma oxygen tension because it determines the oxygen saturation of haemoglobin. The calibre of vessels is determined by the degree of binding of the vasodilator nitric oxide (NO) by oxygenated haemoglobin in forming S-nitrosohaemoglobin.2 In the presence of a coronary artery occlusion, upstream vasoconstriction by oxygen reduces blood flow, limiting the delivery of erythrocytes and hence oxygen availability. However, this only applies over the small range of inspired oxygen concentrations used in oxygen supplementation, because the vasoconstriction is limited by the sites available for NO binding by oxyhaemoglobin. Using 100% oxygen under hyperbaric conditions, plasma oxygen levels may be increased to more than compensate for the loss of oxygen transport by erythrocytes. Boerema et al.3 demonstrated this experimentally in 1960, showing that life is possible without blood when breathing oxygen under hyperbaric conditions.

Higher plasma oxygen concentrations greatly increase the concentration gradient for the transport of oxygen to tissues; at two atmospheres absolute breathing 100% oxygen the concentration gradient is increased ten-fold. This explains the reduction of myocardial infarct size demonstrated experimentally using hyperbaric oxygenation. Beasley et al. do not reference the controlled trials of oxygen treatment under hyperbaric conditions. A controlled study of hyperbaric oxygen in myocardial infarction published in 19734 demonstrated benefit, especially in cardiogenic shock, and the paper includes ECG tracings showing abnormalities improving as the patients were pressurized. More recently, a controlled trial has shown the benefit of combining hyperbaric oxygen treatment with thrombolysis.5
Macrophage Migration Inhibitory Factor Promotes Tumor Growth in the Context of Lung Injury and Repair
Authors: Douglas Arenberg, Tracy R. Luckhardt, Shannon Carskadon, Liujian Zhao, Mohammad A. Amin, Alisa E. Koch
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Tissue injury and repair involve highly conserved processes governed by mechanisms that can be co-opted in tumors. We hypothesized that soluble factors released during the repair response to lung injury would promote orthotopic tumor growth.Objectives: To determine whether lung injury promoted growth of orthotopic lung tumors and to study the molecular mechanisms.Methods: We initiated lung injury in C57Bl6 mice using different stimuli, then injected Lewis lung carcinoma cells during the repair phase. We assessed tumor growth 14 days later. We measured tumor angiogenesis, cytokine expression, proliferation, and apoptosis.Measurements and Main Results: Regardless of the mechanism, injured lungs contained more numerous and larger tumors than sham-injured lungs. Tumors from injured lungs were no more vascular, but had higher levels of proliferation and reduced rates of apoptosis. The cytokine macrophage migration inhibitory factor (MIF) was highly expressed in both models of tissue injury. We observed no increase in tumor growth after lung injury in MIF knockout mice. We induced lung-specific overexpression of MIF in a double-transgenic mouse, and observed that MIF overexpression by itself was sufficient to accelerate the growth of orthotopic Lewis lung carcinoma tumors.Conclusions: Lung injury leads to increased expression of the cytokine MIF, which results in protection from apoptosis and increased proliferation in orthotopic tumors injected after the acute phase of injury.
Comparison of agreement between different measures of blood pressure in primary care and daytime ambulatory blood pressure
Authors: P. Little
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective</b>: To assess alternatives to measuring ambulatory pressure, whichbest predicts response to treatment and adverse outcome. <b>Setting</b>: Three general practices in England <b>Design</b>: Validation study <b>Participants</b>: Patients with newly diagnosed high or borderline high bloodpressure; patients receiving treatment for hypertension but with poor control. <b>Main outcome measures</b>: Overall agreement with ambulatory pressure; prediction of high ambulatory pressure (&gt;135/85 mm Hg) and treatment thresholds. <b>Results</b>: Readings made by doctors were much higher than ambulatory systolic pressure (difference 18.9 mm Hg, 95% confidence interval 16.1 to 21.7), as were recentreadings made in the clinic outside research settings (19.9 mm Hg,17.6 to 22.1). This applied equally to treated patients with poor control (doctor <i>v</i> ambulatory21.4 mm Hg, 17.3 to 25.4). Doctors9 and recent clinic readings ranked systolic pressure poorly compared with ambulatory pressure and other measurements (doctor <i>r</i>=0.46; clinic 0.47; repeated readings by nurse 0.60; repeated self measurement 0.73; home readings 0.75) and were not specific at predicting high blood pressure(doctor 26%; recent clinic 15%; nurse 72%; patient in surgery 81%; home 60%), with poor likelihood ratios for a positive test (doctor 1.2; clinic 1.1; nurse 2.1, patient in surgery 4.7; home 2.2). Nor were doctor or recent clinic measures specific in predicting treatment thresholds. <b>Conclusion</b>: The "white coat" effect is important in diagnosing and assessing control of hypertension in primary care and is not a research artefact. If ambulatory or home measurements are not available, repeated measurements by the nurse or patient should result in considerably less unnecessary monitoring, initiation, or changing of treatment. It is time to stop using high blood pressure readings documented by general practitioners to make treatment decisions
Comment on: Kan et al. A Systematic Review and Meta-analysis of the Association Between Depression and Insulin Resistance. Diabetes Care 2013;36:480–489
Authors: Tomoyuki Kawada
Journal: Diabetes Care (2013)

Kan et al. (1) conducted a meta-analysis on the relationship between depression and insulin resistance (IR), targeting 25 datasets from 18 studies. They calculated the pooled odds ratio using random-effects models and observed a small but significant association between depression and IR.

Before their results can be accepted, I would like to express two concerns in relation to their meta-analysis. First, Kan et al. included articles adopting different definitions for depression. In this connection, they mentioned that the magnitude …
Aortic Valve Perforation in Bacterial Endocarditis
Authors: RALPH TOMPSETT, GLENN D. LUBASH
Journal: Circulation (1961)

This report describes 10 patients with bacterial endocarditis who during observation developed signs of dynamic aortic insufficiency or experienced marked worsening of the manifestations of pre-existing aortic insufficiency. The autopsy findings in these patients provide evidence that the clinical signs were associated with perforation or rupture of the aortic valve cusps. It is suggested that this sequence of events in the course of bacterial endocarditis is common and that its occurrence must be regarded as an ominous prognostic sign.
Localization of Infection in HIV Antibody Positive Patients With Fever Comparison of the Efficacy of Ga-67 Citrate and Radiolabeled Human IgG
Authors: JOHN R. BUSCOMBE, WIM J.G. OYEN, FRANS H.M. CORSTENS, PETER J. ELL, ROBERT F. MILLER
Journal: Clinical Nuclear Medicine (1995)

Patients who are human immunodeficiency virus (HIV) antibody positive are at increased risk of life threatening infection. Scintigraphic imaging with Ga-67 citrate has been used to identify the presence and site of focal infection. However, focal accumulation of Ga-67 is not specific for Infection. A retrospective study was performed to compare the accuracy of Ga-67 citrate and pooled human polyclonal immunogiobulin G (HIG) labeled with Tc-99m HIG and In-111 HIG in identifying infection In HIV antibody positive patients. Twenty-five studies were performed using Ga-67 and Tc-99m HIG were compared with a second group of 25 studies using ln-111 HIG in HIV antibody positive patients presenting with fever, but without localizing symptoms or signs. In-111 HIG identified 20 of 22 sites of infection and also accumulated in 5 sites without Infection (accuracy = 90%). This was significantly more accurate (X2, P < 0.05) than Ga-67 which identified 19 of 20 sites of infection, but accumulated in 18 sites without infection (accuracy = 74%) and Tc-99m HIG which identified infection in 11 of 20 sites, but accumulated in 8 sites without infection (accuracy = 77%). There was no significant difference between the accuracy of Ga-67 and Tc-99m HIG. From this preliminary study In-111 HIG would seem to be the best agent for identifying infection in HIV antibody positive patients with fever.
747-5 Transesophageal Echocardiographic Quantitation of Mitral Leaflet Thickness in Patients with Mitral Valve Prolapse
Authors: Eric K. Louie, David Langholz, William J. Mackin, Diane E. Wallis, William R. Jacobs, Patrick J. Scanlon.
Journal: Journal of the American College of Cardiology (1995)
Glyburide-Induced Hypoglycemia and Ranitidine
Authors: Kelvin Lee, Ruth Mize, Steven R. Lowenstein
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 August 1987Glyburide-Induced Hypoglycemia and RanitidineKELVIN LEE, M.D., RUTH MIZE, M.D., STEVEN R. LOWENSTEIN, M.D., M.P.H.KELVIN LEE, M.D.Search for more papers by this author, RUTH MIZE, M.D.Search for more papers by this author, STEVEN R. LOWENSTEIN, M.D., M.P.H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-2-261 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We report a new drug interaction—the potentiation of the hypoglycemic effects of glyburide by ranitidine.A 72-year-old man was hospitalized with hematemesis. He had a history of hypertension and diabetes mellitus, the latter treated for 6 months with glyburide, 5 mg/d. His serum glucose levels were consistently 120 to 130 mg/dL. Endoscopic examination showed erosive esophagitis. Ranitidine, 150 mg twice a day, was started on the second hospital day. While he was hospitalized, his glucose level ranged from 126 to 178 mg/dL. Liver and renal function tests and electrolyte levels were normal. He was discharged 4 days...References1. JACKSONBRESSLER JR Clinical pharmacology of sulfonylurea hypoglycemic agents. Drugs. 1981;22:211-45, 295-320. CrossrefMedlineGoogle Scholar2. SKILLMANFELDMAN TJ. The pharmacology of sulfonylureas. Am J Med. 1981;70:361-72. CrossrefMedlineGoogle Scholar3. FEELYPEDEN JN. Enhanced sulfonylurea-induced hypoglycemia with cimetidine. Br J Clin Pharmacol. 1983;16:607P. Google Scholar4. MACWALTEREL DEBANIFEELYSTEVENSON RAJI. Potentiation by ranitidine of the hypoglycemic response to glypizide in diabetic patients. Br J Clin Pharmacol. 1985;19:121p. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCYP2C metabolism of oral antidiabetic drugs - impact on pharmacokinetics, drug interactions and pharmacogenetic aspectsDrug-Induced HypoglycaemiaOral antidiabetic drug metabolism: pharmacogenomics and drug interactionsDrug Interactions of Clinical Importance with Antihyperglycaemic AgentsThe effect of ranitidine on the pharmacokinetics of rosiglitazone in healthy adult male volunteersThe drug interaction potential of ranitidine: An update 1 August 1987Volume 107, Issue 2Page: 261-262KeywordsDiabetes mellitusDrug interactionsDrugsGlucoseHypertensionHypoglycemiaHypoglycemicsLiver Issue Published: 1 August 1987 PDF downloadLoading ...
New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease.
Authors: P A Price, J G Parthemore, L J Deftos
Journal: Journal of Clinical Investigation (1980)

gamma-Carboxyglutamic acid-containing protein of bone (BGP) is an abundant noncollagenous protein of mammalian bone. BGP has a molecular weight of 5,800 and contains three residues of the vitamin K-dependent amino acid, gamma-carboxyglutamic acid. We have applied a radioimmunoassay based on calf BGP for the measurement of the protein in the plasma of 109 normal humans and 112 patients with various bone diseases. BGP in human plasma was demonstrated to be indistinguishable from calf BGP by assay dilution studies and gel permeation chromatography. The mean (+/- SE) concentration of BGP in normal subjects was 6.78 (+/- 0.20) ng/ml, 7.89 (+/- 0.32) for males and 4.85 (+/- 0.35) for females. Plasma BGP was increased in patients with Paget's disease of bone, bone metastases, primary hyperparathyroidism, renal osteodystrophy, and osteopenia. Plasma BGP did correlate with plasma alkaline phosphatase (AP) in some instances, but there were dissociations between the two. It was additionally observed that patients with liver disease had normal plasma BGP despite increased plasma AP, a reflection of the lack of specificity of AP measurements for bone disease. Our studies indicate that the radioimmunoassay of plasma BGP can be a useful and specific procedure for evaluating the patient with bone disease.
Rhinovirus-Induced Immune Response in Nasal Epithelial Cells
Authors: Marek L. Kowalski, Agnieszka Olszewska-Ziober, Malgorzata Pawelczyk, Aleksandra Piechota-Polanczyk, Sylwia Moskwa, Marzanna Jarzebska, Agnieszka Jablonska, Anna Globinska
Journal: Journal of Allergy and Clinical Immunology (2015)