tbuckley/cabot-search huggingface dataset:
347. Long-Term Gene Expression and Phenotypic Correction of FANCC Deficient Lymphoblastoid Cells Using the Sleeping Beauty Transposon System
Authors: Shannon A. Wadman, Karl J. Clark, Perry B. Hackett, R Scott McIvor, Jeffrey J. Essner
Journal: Molecular Therapy (2005)

We are moving forward with development of our proprietary Sleeping Beauty Transposon (SBT) system for the treatment of Fanconi anemia (FA) via ex vivo electroporation of hematopoietic stem cells. FA is an inherited recessive disorder caused by deficiency in one of a number of genes whose products form a complex involved in DNA repair. The primary hematological hallmarks of the disease are aplastic anemia, bone marrow failure, and increased susceptibility to leukemias thought to be caused by defective cellular mechanisms for DNA repair. Allogeneic bone marrow transplantation is currently the only curative treatment for these aspects of the disease and despite improvements in clinical protocols over the years difficulties with allotransplants for FA still persist. The primary goal of this study is to evaluate the potential of SBT vectors carrying the FANCC gene to effectaffect transposition and establish long-term expression in FANCC-deficient cell populations after introduction by electroporation. Additionally, we show that integration of FANCC transposons can correct the sensitivity of lymphoblastoid cell lines (LCL) derived from FANCC patients to DNA damaging agents such as mytomycin C. We constructed a transposon containing a PGK promoter to regulate transcription of the normal human FANCC cDNA sequence. The vector containing the transposon also includes a ubiquitin promoter regulating expression of the SB transposase gene, encoded outside of the transposon. The SBT-FANCC vector was introduced via electroporation into FANCC deficient and normal control LCLs. Long-term maintenance of FANCC complementation in the FANCC-deficient cells was observed as a sustained reduction in sensitivity to mitomycin C similar to normal controls. In addition, the isolation and molecular characterization of clonal populations of these FANCC-complemented cells demonstrated FANCC transposon integration into the genome by SB mediated transposition. Preliminary results using SBT vectors in K562 cells suggest that a transposase provided on a separate plasmid may increase the efficiency of transposition. As a result, studies are also underway to characterize the efficacy of the SBT-FANCC vector described above compared to a similar vector in which the transposase is supplied either by a separate plasmid or by a SB-encoding mRNA. These studies demonstrate molecular feasibility of the SB transposon system in combination with electroporation-based cell loading technology for genetic therapy of Fanconi anemia.
Animal Models of Cholesterol Gallstone Disease
Authors: Thomas R. Holzbach
Journal: Hepatology (1984)

There is no genetically susceptible, spontaneous and naturally occurring animal model for human cholesterol cholelithiasis. The disease has been reported to occur spontaneously only rarely in some primates. The human disease is probably multifactorial; therefore, the finding or development through inbreeding of a spontaneous genetic model is unlikely. The two most popular animals in use today as models are rodent species: hamster and prairie dog. Despite widely different means of dietary induction of the disease in the two, the feature common to both is cholesterol overload. In the case of the essential fatty acid-deficient hamster, the predominant defect is a unique endogenous overproduction through increased total body synthesis of cholesterol. In the prairie dog, the cholesterol overload is simply exogenous due to massive and rapid intestinal absorption. Neither model is remotely physiological. Although a number of useful aspects of the lithogenic process can be studied using these models, certain changes apparently associated with the formation of gallstones under these conditions may in part be a function of the unphysiological dietary requirements for induction of the disease.
Promotion of cardiac differentiation of brown adipose derived stem cells by chitosan hydrogel for repair after myocardial infarction
Authors: Haibin Wang, Jinxin Shi, Yan Wang, Yujing Yin, Liman Wang, Jianfeng Liu, Zhiqiang Liu, Cuimi Duan, Ping Zhu, Changyong Wang
Journal: Biomaterials (2014)
Association between Admission Mean Platelet Volume and ST Segment Resolution after Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Özgür Kırbaş, Özge Kurmuş, Cemal Köseoğlu, Sina Ali, Recai Alemdar, Bilge Duran, Mehmet Bilge
Journal: Journal of the American College of Cardiology (2013)
STAPHYLOCOCCUS TOXOID IN THE TREATMENT OF PUSTULAR DERMATOSES
Authors: C. E. Dolman
Journal: JAMA (1934)

<h3>To the Editor:—</h3> The article by Kindel and Costello under this title inThe Journal, April 21, is open to several criticisms. The authors apparently set out to make a purely clinical assay of the efficacy of a particular commercial preparation of staphylococcus toxoid in the treatment of pustular dermatoses. Among a group of forty-two patients, including twenty-eight with acne vulgaris, eight with sycosis vulgaris and only six with furunculosis, a slight improvement was noted in eight, while thirty-four were unimproved or worse after several injections of staphylococcus toxoid. The authors concluded that these were unsatisfactory results, and one does not cavil at their conclusion. But their further observation that "caution should be exercised in becoming over-enthusiastic about the value of staphylococcus toxoid until further reports confirm or deny our observations" seems entirely superfluous and unwarranted. Admittedly, excessive enthusiasm of the type the authors probably had in mind exerts a
You Can Prevent Illness
Authors: Frederick Stenn
Journal: JAMA (1960)

Dr. Pinckney elucidates the essential principles of preventive medicine for the layman. He writes with a simple, charming style about immunization against the infectious and contagious diseases; prevention of accidents at home and in the street; safety in industry; periodic examinations for glaucoma, tuberculosis, and diabetes; precautions in travel; management of constipation and obesity; emotional problems; and radiation hazards. He urges each family to keep its own health records and suggests the appointment of a family health officer. This book should serve as a helpful, practical, and accurate guide for the doctor's patients.
Civilian Physician Contribution to the Active Military
Authors: Robert L. Bradley
Journal: JAMA (1977)

The civilian physician contribution to the Armed Forces of the United States has seldom been heralded in the historic chronology of this country and even less in its military annals. Yet at no time in peace or war has the regular military establishment been staffed to meet its medical requirements without aid from its civilian counterpart (Figure). In our War for Independence, essentially all our forces, support and combat, emerged from the civil ranks. The United States, born in war and involved in three major conflicts and innumerable smaller ones, remains distrustful of a strong military, yet its ability to mobilize in time of war is equaled only by its haste to demobilize when peace is secured. Our peacetime military has been pared in years past to a bare housekeeping strength, and the active medical corps has shared the severity of force reduction. Physicians for the military cannot be produced
Methods of Exposure Assessment: Lead-Contaminated Dust in Philadelphia Schools
Authors: Charles V. Shorten, Marijane K. Hooven
Journal: Environmental Health Perspectives (2000)

This study was conducted to develop a method that would accurately assess children's exposure to lead in schools in Philadelphia, Pennsylvania. We examined three wipe sample protocols: one included accessible surfaces such as desktops and windowsills, the second included inaccessible surfaces such as the top of filing cabinets and light fixtures, and the third included hand wipes of the study participants. Surface wipes were collected at 10 locations from accessible and inaccessible classroom surfaces (n = 11 at each location) and from the palms of student subjects in the same locations (n = 168). We found a significant difference in lead dust concentrations determined by the three protocols (F = 4.619; 2,27 degrees of freedom; p = 0.019). Lead dust concentrations were significantly elevated at the inaccessible surfaces yet they were uniformly low on the accessible surfaces and the children's palms. These findings were consistent with observed changes in blood lead levels of study participants: after 6 months of exposure to the study locations, 156 of 168 children experienced no change in blood lead level, whereas 12 experienced only a minimal change of 1-2 microg/dL. The mere presence of lead in inaccessible dust in the school environment does not automatically constitute a health hazard because there may not be a completed exposure pathway.
Serum Ferritin Levels and Hepatocellular Carcinoma: the Cart or the Horse?
Authors: Lawrie W. Powell, June W. Halliday
Journal: Hepatology (1990)

Previous studies from this laboratory support the view that increased serum ferritin levels are associated with an increased risk of primary hepatocellular carcinoma (PHC). We have tested this hypothesis in a population of Korean patients with chronic liver disease followed for development of PHC. Serum ferritin levels were measured over time in 249 patients with liver diseases (mostly chronic) followed for 2 to 17 years in Seoul, Korea. Most of the patients were chronically infected with hepatitis B virus. During the first 8 months of follow–up, there were no cases of PHC and no deaths. During this same period, no patient had a serum ferritin level initially below 300 ng/ml and rising above 300 ng/ml, but some patients with ferritin levels above 300 ng/ml experienced decreases to below 300 ng/ml. Therefore, patients were grouped by ferritin level during the first 8 months of follow–up into 3 categories according to the above criteria. Multivariate analysis showed that consistently elevated ferritin levels (category 3) were significantly associated with the development of PHC. Men were more likely to have elevated ferritin levels than women and were at higher risk of developing PHC. Men who were chronically infected with HBV and had ferritin levels above 300 ng/ml had a 50% chance of developing PHC during the follow–up period, compared with a 20% risk of PHC for men with lower ferritin levels (categories 1 and 2). This elevated risk of PHC in men with elevated ferritin levels was confined to the first 3 years of follow–up.
Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticosteroids
Authors: E.S. Mendes, A. Pereira, I. Danta, R.C. Duncan, A. Wanner
Journal: European Respiratory Journal (2003)

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma. A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean+/-SD Qaw normalised for anatomical dead space was 53.1+/-1.4 microL x min(-1) x mL(-1) in healthy subjects (n=10) and 67.8+/-3 microL x min(-1) x mL(-1) in asthmatics (n=10). All GS caused a transient decrease in Qaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decrease Qaw by 20%, from the baseline, 30-min postdrug inhalation. Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids.
C1qTNF–related protein-1 (CTRP-1): a vascular wall protein that inhibits collagen-induced platelet aggregation by blocking VWF binding to collagen
Authors: Gerald Lasser, Prasenjit Guchhait, Jeff L. Ellsworth, Paul Sheppard, Ken Lewis, Paul Bishop, Miguel A. Cruz, Jose A. Lopez, Joachim Fruebis
Journal: Blood (2005)
Muscle-Directed Gene Transfer and Transient Immune Suppression Result in Sustained Partial Correction of Canine Hemophilia B Caused by a Null Mutation
Authors: Roland W. Herzog, Jane D. Mount, Valder R. Arruda, Katherine A. High, Clinton D. Lothrop
Journal: Molecular Therapy (2001)

The X-linked bleeding disorder hemophilia B is caused by absence of functional blood coagulation factor IX (F9) and can be treated by adeno-associated viral (AAV) mediated gene transfer to skeletal muscle. The safety of this approach is currently being evaluated in a phase I clinical trial. Efficacy of this and several other gene therapy strategies has been addressed in hemophilia B dogs, an important preclinical model of the disease. While previously published data demonstrated sustained expression of canine F9 in dogs with a missense mutation in the gene F9, we show here that AAV-mediated canine F9 gene transfer to skeletal muscle of hemophilia B dogs carrying a null mutation of F9 (causing an early stop codon and an unstable mRNA) results in induction of inhibitory anti-canine F9 at comparable vector doses (1×1012 vector genomes/kg). Thus, the risk of inhibitor formation following AAV-mediated F9 gene therapy may be influenced by the nature of the underlying mutation in F9. Transient immune suppression with cyclophosphamide at the time of vector administration blocked formation of anti-canine F9 antibodies in the one animal treated with this approach. Treatment with this combination of gene transfer and transient immune modulation has resulted in sustained expression (>8 months) of canine F9 at levels sufficient for partial correction of coagulation parameters.
Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes.
Authors: J H Leech, J W Barnwell, L H Miller, R J Howard
Journal: The Journal of Experimental Medicine (1984)

We have identified strain-specific antigens with Camp and St. Lucia strains of P. falciparum of Mr approximately 285,000 and approximately 260,000, respectively. These strain-specific antigens were metabolically labeled with radioactive amino acids, indicating that they were of parasite origin rather than altered host components. These proteins had the properties of a molecule exposed on the surface of infected erythrocytes (IE). First, the proteins are accessible to lactoperoxidase-catalyzed radioiodination of IE. Second, the radioiodinated proteins were cleaved by low concentrations of trypsin (0.1 microgram/ml). Third, these antigens were immunoprecipitated after addition of immune sera to intact IE. Fourth, the strain-specific immuno-precipitation of these proteins correlated with the capacity of immune sera to block cytoadherence of IE in a strain-specific fashion. Fifth, the strain-specific antigen had detergent solubility properties (i.e., insolubility in 1% Triton X-100, solubility in 5% sodium dodecyl sulfate) similar to the variant antigen of P. knowlesi, which has been proven to be a malarial protein exposed on the erythrocyte surface.
A systematic review and meta-analysis of pregnancy as a protective factor against rheumatoid arthritis
Authors: Ian C Scott, Cathryn M Lewis, Sophia Steer, Andrew Cope
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> The female preponderance of rheumatoid arthritis (RA) implies that reproductive factors may play an important role in its pathogenesis. Although several studies have shown an inverse association between previous pregnancy and RA development this finding has not been consistently reproduced and the precise relationship remains uncertain. The authors therefore undertook a systematic review and meta-analysis of observational studies examining pregnancy as a risk factor for RA. Our primary aim was to establish if pregnancy is associated with the risk of RA. Our secondary aim was to evaluate if this risk varies by rheumatoid factor (RF)/anticyclic citrullinated peptide antibody (ACPA) status. <h3>Materials and methods</h3> Search strategy: the authors searched Medline/EMBASE (1947 November 2011) using the search terms 'rheumatoid arthritis.mp' or 'arthritis, rheumatoid/' and 'pregnancy.mp' or 'pregnancy/' (limited to 'humans'). The Scottish Intercollegiate Guidelines Network observational study filter was applied. Included manuscript bibliographies were reviewed. Inclusion Criteria: 1) case-control/cohort studies; 2) examining relationships between pregnancy and RA risk; 3) reporting effect size data as OR/RR with 95% CIs in parous versus nulliparous females (or providing crude data allowing their calculation). Statistics: Due to the low prevalence of RA, ORs/RRs were used interchangeably. Due to heterogeneity a random effects model was used to estimate summary ORs/RRs. Crude and adjusted ORs/RRs were evaluated separately. <h3>Results</h3> 248 citations were identified. 14 studies were included – 10 case-control (evaluating 1967 cases and 6113 controls) and four cohort studies (evaluating 8118 incident RA cases from 2 308 533 individuals). Crude and adjusted ORs/RRs were available for eight studies; three cohort studies reported adjusted and three case-control reported crude ORs/RRs only. Previous pregnancy was inversely associated with RA. The unadjusted summary OR for RA in parous versus nulliparous women was 0.76 (0.63–0.91). The adjusted summary OR for RA was also significant at 0.81 (0.68–0.96). Only a single study stratified risk by RF status- no significant relationship was identified with either subset. No studies evaluated risk by ACPA status. <h3>Conclusions</h3> Our systematic review shows an inverse relationship between previous pregnancy and RA. Although this indicates a likely protective effect of parity on the risk of RA development caution is required because the largest risks were observed in case-control studies, which are open to recall bias and cannot prove causality. The authors consider that further prospective cohort studies are required, evaluating cases by ACPA status, to better discern what risk factors are important in RA subset pathogenesis.
An introduction to diagnostic enzymology.
Authors: Camillo Artom
Journal: JAMA (1963)

The ever increasing use of enzyme determinations as aids to clinical diagnosis has led to the accumulation of a large number of results of widely different value and significance. The stated purposes of Wilkinson's book are to critically review the available information and to offer to the clinician a guide in choosing those determinations which, in the present status of our knowledge, seem to be most appropriate to a given clinical condition. In the reviewer's opinion, these aims have been quite successfully attained. The general concepts of the structure, mode of action, terminology, and classification of enzymes are first presented in clear, concise language. Next, the author briefly outlines the mechanisms through which changes in the enzymatic activities of body fluids occur in disease, and points out how and to what extent such changes may supply useful diagnostic information. Further considerations and some plausible speculations concerning the source, mechanisms of
Postural relief of dyspnoea in severe chronic airflow limitation: relationship to respiratory muscle strength.
Authors: S O'Neill, D S McCarthy
Journal: Thorax (1983)

Maximal static inspiratory and expiratory pressures (Pimax and Pemax) were measured in six different positions in 40 patients with advanced chronic airflow limitation and in 140 normal subjects to determine whether posture influences respiratory muscle strength. Patients with chronic airflow limitation were studied on days 1 and 5 of an acute exacerbation. There was no postural effect on maximal static pressures in the normal subjects. We divided our patients with chronic airflow limitation into "moderate" and "severe" groups on the basis of a Pimax in the standing position greater or less than 35 cm H2O. The seated leaning-forward position was the preferred posture in 22 of the 23 "severe" patients and 13 of the 17 "moderate" patients. Pimax was greater in the seated leaning-forward position than in the other positions studied (p less than 0.001) on days 1 and 5 in the "severe" patients and (p less than 0.05) on day 5 in the "moderate" patients. Posture had no influence on Pemax in patients with chronic airflow limitation. There was a significant improvement in both Pimax (p less than 0.01 for the "severe" group and p less than 0.05 for the "moderate" group) and Pemax (p less than 0.01 for both groups) between days 1 and 5. The seated leaning-forward position was the optimum posture for the patients to generate maximum inspiratory pressures and to obtain greatest subjective relief of dyspnoea.
Association of Arsenic and Metals with Concentrations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D among Adolescents in Torreón, Mexico
Authors: Rachel D. Zamoiski, Eliseo Guallar, Gonzalo G. García-Vargas, Stephen J. Rothenberg, Carol Resnick, Marisela Rubio Andrade, Amy J. Steuerwald, Patrick J. Parsons, Virginia M. Weaver, Ana Navas-Acien, Ellen K. Silbergeld
Journal: Environmental Health Perspectives (2014)

Background: Limited data suggest that lead (Pb), cadmium (Cd), and uranium (U) may disrupt vitamin D metabolism and inhibit production of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active vitamin D metabolite, from 25-hydroxyvitamin D [25(OH)D] in the kidney.Objectives: We evaluated the association between blood lead (BPb) and urine arsenic (As), Cd, molybdenum (Mo), thallium (Tl), and U with markers of vitamin D metabolism [25(OH)D and 1,25(OH)2D].Methods: We conducted a cross-sectional study of 512 adolescents in Torreón, a town in Mexico with a Pb smelter near residential areas. BPb was measured using atomic absorption spectrometry. Urine As, Cd, Mo, Tl, and U were measured using inductively coupled plasma mass spectrometry. Serum 25(OH)D and 1,25(OH)2D were measured using a chemiluminescent immunoassay and a radioimmunoassay, respectively. Multivariable linear models with vitamin D markers as the outcome were used to estimate associations of BPb and creatinine-corrected urine As and metal concentrations with serum vitamin D concentrations, controlling for age, sex, adiposity, smoking, socioeconomic status, and time outdoors.Results: Serum 25(OH)D was positively associated with urine Mo and Tl [1.5 (95% CI: 0.4, 2.6) and 1.2 (95% CI: 0.3, 2.1) ng/mL higher with a doubling of exposure, respectively]. Serum 1,25(OH)2D was positively associated with urine As and U [3.4 (95% CI: 0.9, 5.9) and 2.2 (95% CI: 0.7, 3.7) pg/mL higher, respectively], with little change in associations after additional adjustment for serum 25(OH)D. Pb and Cd were not associated with 25(OH)D or 1,25(OH)2D concentrations.Conclusions: Overall, our findings did not support a negative effect of As or metal exposures on serum 1,25(OH)2D concentrations. Additional research is needed to confirm positive associations between serum 1,25(OH)2D and urine U and As concentrations and to clarify potential underlying mechanisms.Citation: Zamoiski RD, Guallar E, García-Vargas GG, Rothenberg SJ, Resnick C, Rubio Andrade M, Steuerwald AJ, Parsons PJ, Weaver VM, Navas-Acien A, Silbergeld EK. 2014. Association of arsenic and metals with concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D among adolescents in Torreón, Mexico. Environ Health Perspect 122:1233–1238; http://dx.doi.org/10.1289/ehp.1307861