tbuckley/cabot-search huggingface dataset:
Characteristics of participants with self-reported hemochromatosis or iron overload at HEIRS study initial screening
Authors: James C. Barton, Ronald T. Acton, Catherine Leiendecker‐Foster, Laura Lovato, Paul C. Adams, John H. Eckfeldt, Christine E. McLaren, Jacob A. Reiss, Gordon D. McLaren, David M. Reboussin, Victor R. Gordeuk, Mark R. Speechley, Richard D. Press, Fitzroy W. Dawkins
Journal: American Journal of Hematology (2007)

Abstract There are few descriptions of young adults with self‐reported hemochromatosis or iron overload (H/IO). We analyzed initial screening data in 7,343 HEmochromatosis and IRon Overload Screening (HEIRS) Study participants ages 25–29 years, including race/ethnicity and health information; transferrin saturation (TS) and ferritin (SF) measurements; and HFE C282Y and H63D genotypes. We used denaturing high‐pressure liquid chromatography and sequencing to detect mutations in HJV , TFR2 , HAMP , SLC40A1 , and FTL . Fifty‐one participants reported previous H/IO; 23 (45%) reported medical conditions associated with H/IO. Prevalences of reports of arthritis, diabetes, liver disease or liver cancer, heart failure, fertility problems or impotence, and blood relatives with H/IO were significantly greater in participants with previous H/IO reports than in those without. Only 7.8% of the 51 participants with previous H/IO reports had elevated TS; 13.7% had elevated SF. Only one participant had C282Y homozygosity. Three participants aged 25–29 years were heterozygous for potentially deleterious mutations in HFE2 , TFR2 , and HAMP promoter, respectively. Prevalences of self‐reported conditions, screening iron phenotypes, and C282Y homozygosity were similar in 1,165 participants aged 30 years or greater who reported previous H/IO. We conclude that persons who report previous H/IO diagnoses in screening programs are unlikely to have H/IO phenotypes or genotypes. Previous H/IO reports in some participants could be explained by treatment that induced iron depletion before initial screening, misdiagnosis, or participant misunderstanding of their physician or the initial screening questionnaire. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Abstract 3809: Cardiac-Specific Overexpression of EcSOD Using an AAV9 Vector in Combination with the Cardiac Troponin-T Promoter Inhibits LV Remodeling after Myocardial Infarction
Authors: Konkal-Matt R Prasad, Ronald J Beyers, Yaqin Xu, Brent A French
Journal: Circulation (2008)

Introduction: The wide tissue tropism exhibited by AAV provides for efficient gene transfer throughout the body, but targeting gene expression to cardiomyocytes is desirable for cardiac gene therapy. We hypothesized that targeted overexpression of extracellular superoxide dismutase (EcSOD) via the cardiac Troponin-T (cTnT) promoter would suffice to minimize left ventricular (LV) remodeling after myocardial infarction (MI). Methods: An AAV9 vector expressing EcSOD from the cTnT promoter (AcTnTEcSOD) was injected into 5 wk-old C57 mice via jugular vein (3x10 11 vp/mouse). Western blots, immunohistochemistry &amp; in vitro SOD assays were used to measure EcSOD expression, distribution and activity. Cardiac magnetic resonance (CMR) imaging was performed at baseline (5 wks post-vector injection) and at days 1, 7 &amp; 28 after MI to assess LV volumes (vol) &amp; ejection fraction (EF) as compared to WT mice (n=4). Infarct (IF) sizes were also compared by DE on D1. Results: Systemic injection of the vector (AcTnTEcSOD) provided uniform EcSOD overexpression within cardiomyocytes (Panels A&amp;B) and elevated total cardiac SOD activity by 5.6 fold (p&lt;0.05). On D1 post-MI, IF sizes were similar in vector &amp; WT groups (p=ns). The vector group had significantly lower end-diastolic vol at D7, D28 and lower end-systolic vol at D28 (all p&lt;0.05 by ANOVA, Panels C&amp;D), resulting in improved D28 EF over controls (p=0.02). Conclusions: Cardiac-specific overexpression of therapeutic genes can be achieved by combining highly-efficient AAV9 vectors with cardiac-specific promoters. AAV-mediated, cardiac-restricted overexpression of EcSOD from the cTnT promoter significantly reduces post-MI LV remodeling.
RNA-guided diagnostics and therapeutics for next-generation individualized nanomedicine
Authors: Gennadi V. Glinsky
Journal: Journal of Clinical Investigation (2013)

The absence of reliable quantitative laboratory tests for measurements of microRNAs and other classes of small noncoding RNAs in archived, formalin-fixed, paraffin-embedded human samples with sufficient specificity and sensitivity has significantly limited the development of clinically relevant noncoding RNA–based diagnostic and therapeutic applications. A report by Renwick et al. in this issue of the JCI presents a significant technical and methodological advance toward the development of reliable clinical laboratory-compatible multicolor RNA FISH methodology for molecular diagnostic applications and the near-term prospect of introduction of microRNA-based biomarkers into clinical practice. Further, this work is likely to advance the development of RNA-based therapeutics and next-generation individualized nanomedicine.
Clinical Evaluation of Percent Free Prostate&amp;ndash;Specific Antigen Using the AxSYM System in the Best Analytical Scenario
Authors: M. Gion, R. Mione, P. Barioli, M. Barichello, F. Zattoni, T. Prayer-Galetti, M. Plebani, G. Aimo, C. Terrone, F. Manferrari, G. Madeddu, L. Caberlotto, A. Fandella, C. Pianon, L. Vianello, B. Amoroso
Journal: European Urology (2000)
Permanent Heart Substitution: Better Solutions Lie Ahead
Authors: William S. Pierce
Journal: JAMA (1988)

The articles by DeVries et al in this issue ofThe Journaldocument in the scientific literature the events surrounding the much publicized permanent heart replacement using the Jarvik-7 pneumatically powered artificial heart. Their reports define the serious problems that have cast a dark shadow on the currently available pneumatic heart: thromboemboli and infections. Unfortunately, given the present state of the art and science, these problems will not be readily solved. While the tenor of these articles is positive and DeVries and coworkers imply that additional permanent implants will be performed, the suggested solutions to these problems, primarily alterations in patient management, seem unlikely to reduce substantially the incidence of complications. Accordingly, adding patients to this series will serve only to document further the magnitude of the complications rather than to demonstrate an acceptable life-style in the recipient. During the past several years, similar pneumatically powered mechanical hearts have been
Combinatorial RNAi: A Winning Strategy for the Race Against Evolving Targets?
Authors: Dirk Grimm, Mark A Kay
Journal: Molecular Therapy (2007)

The ability to use double-stranded RNA to inhibit gene expression sequence-specifically (RNA interference, or RNAi) is currently revolutionizing science and medicine alike. Numerous pre-clinical studies are evaluating RNAi as a novel therapeutic modality in the battle against gain-of-function autosomal dominant diseases, cancer, and viral infections. One emerging concern is that RNAi mono-therapies might ultimately fail to control viruses that can escape silencing by mutation and/or RNAi suppression. Thus, sophisticated strategies are being developed that aim to avert viral resistance by combining RNAi effectors with each other or with further gene expression inhibitors. Several reports already validate this new concept of "combinatorial RNAi" (coRNAi) and illustrate its versatility by describing co-expression of RNAi triggers directed against single or multiple, viral or cellular, targets. Other studies document the successful delivery of these triggers with additional RNA- or protein-based silencers. Moreover, vectors have been engineered to blend RNAi-mediated gene inhibition with conventional gene replacement strategies. Collectively, these efforts open up exciting new therapeutic avenues but could also augment the inherent risks of RNAi technology, including immune responses, off-targeting, and oversaturation of endogenous pathways. Here, we critically review all coRNAi strategies and discuss the requirements for their transition into clinical application.
Abstract 2385: Identification of a molecular marker for cetuximab sensitivity and development of a novel combination therapy for non-small cell lung cancers.
Authors: Miyako Takata, Hiroki Chikumi, Kosuke Yamaguchi, Jun Kurai, Masaki Nakamoto, Naoto Burioka, Tadashi Igishi, Eiji Shimizu
Journal: Cancer Research (2013)

Abstract The epidermal growth factor receptor (EGFR) is an important molecular target for non-small-cell lung cancers (NSCLCs). A recent phase III study (the FLEX study) revealed that the combination of the anti-EGFR antibody cetuximab with conventional chemotherapy improved the survival of patients with NSCLCs. However, the survival benefit was only about 5 weeks. Therefore, the identification of a molecular marker for cetuximab sensitivity is urgently needed. In this study, we investigated a new molecular marker for cetuximab sensitivity and developed a combination therapy to improve the effectiveness of cetuximab. First, we established a NSCLC cell line that showed resistance to cetuximab by culturing a parental sensitive NSCLC cell line in the presence of increasing concentrations of cetuximab. Next, we performed microarray analysis to compare the gene expression patterns of cetuximab-sensitive and -resistant cell lines. Using pathway analysis, we found that the Akt and Wnt pathways were significantly activated in the resistant cell line as compared to their activation in the sensitive cell line. We confirmed this result by performing western blot analysis, which showed Akt phosphorylation and beta-catenin dephosphorylation in the resistant cell line. Therefore, the activation status of either the Akt or Wnt pathway is the candidate pathway that influences cetuximab sensitivity. Finally, we focused on the Akt pathway and treated both resistant and parental sensitive cell lines with the PI3-K inhibitor LY294002 in combination with cetuximab. This combination therapy induced a synergistic growth-inhibiting effect in both cell lines. The data suggest that the activation status of the Akt pathway is one of the markers for cetuximab sensitivity and the combination of an Akt pathway inhibitor and cetuximab would be a promising anti-EGFR therapy for NSCLCs. Citation Format: Miyako Takata, Hiroki Chikumi, Kosuke Yamaguchi, Jun Kurai, Masaki Nakamoto, Naoto Burioka, Tadashi Igishi, Eiji Shimizu. Identification of a molecular marker for cetuximab sensitivity and development of a novel combination therapy for non-small cell lung cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2385. doi:10.1158/1538-7445.AM2013-2385 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
On the Mortality of Infants in Foundling Institutions, and Generally, as Influenced by the Absence of Breast-Milk
Authors: C. H. F. Routh
Journal: BMJ (1858)

11 ec foregoing obeserx ations are entirely meteorological, and such as could be accurately taken without the aid of astrono- mical instrumenets.They describe the condition of the atmo- sphere, the amount of clouds, the degree of daylight, moisture, barometrical pressure, and thermometrical temperature (Fah.),
Gestational Diabetes: Infant and Maternal Complications of Pregnancy in Relation to Third-Trimester Glucose Tolerance in the Pima Indians
Authors: David J Pettitt, William C Knowler, H Robert Baird, Peter H Bennett
Journal: Diabetes Care (1980)

A modified oral glucose tolerance test was done during the third trimester in 811 pregnancies in Pima Indian women over a 13-yr period, and maternal and fetal complications were documented. Diabetes was known to be present in 51 pregnancies. Among those who were not previously known to have diabetes, rates of perinatal mortality, macrosomia, toxemia, and cesarean section varied directly with glucose concentration, but congenital malformation and prematurity rates did not. Rates of all of these complications were higher in known diabetic women than in the remainder of the population. In addition to glucose concentrations, maternal weight and age were predictive of macrosomia and toxemia. Third-trimester glucosuria was found to be of very limited value as a screening procedure for gestational diabetes. In 233 women followed for 4-8 yr, the third-trimester glucose concentration was highly predictive of the subsequent incidence of diabetes.
Side effects due to treatment of hypertension with prazosin.
Authors: M J Bendall, K H Baloch, P R Wilson
Journal: BMJ (1975)

completely healthy, without neurological symptoms or Kayser-Fleischer ring, and liver test results were normal.Serum caeruloplasmin1 was slightly decreased at 95 mg/l (normal value in our laboratory 130-270 mg/l), and urine copper excretion was raised at 1-27 1Lmol/24th (81 gg/24 h) (normal value 0-78 Lmol/24 h (50 sg/24 h)).After a diagnostic test with 64Cu2 a preclinical stage of Wilson's disease was diagnosed.He was given D-penicillamine 1 g/day.No side effects were observed during the first 13 months.In May 1973 he developed weakness of the right ocular muscles; in particular, ptosis was more pronounced at the end of the day.During the next 10 days the weakness became worse and left ptosis developed; no other muscles showed weakness.After edrophonium chloride 10 mg intravenously rapid opening of both eyes was noted.Electromyography and immunological investigations were not performed.Penicillamine was withdrawn and he was given neostigmine.After six weeks he showed no symptoms of myasthenia.Eight months later he still had no neurological symptoms.Laboratory investigations confirmed the diagnosis of Wilson's disease.An electromyo- gram and a laminagram of the mediastinum were normal.Though weak antibodies to smooth muscles were detected in the serum by indirect immuno- fluorescence no antinuclear antibodies were found.The patient was again given D-penicillamine 0 75 g/day.During the next 10 months he had no side effects.Antibodies to smooth muscles were detected in May and June 1974 but not in November 1974.The myastlienic syndrome which developed in this patient was probably induced by penicillamine, just as other autoimmune syn- dromes have occurred after long-term treatment with this drug.3
Treatment of Gastrointestinal Motility Disorders in Pregnancy
Authors: Stephen M. Picca
Journal: Annals of Internal Medicine (1993)

Letters1 October 1993Treatment of Gastrointestinal Motility Disorders in PregnancyStephen M. Picca, MD and John Fiordalisi, MDStephen M. Picca, MDSearch for more papers by this author and John Fiordalisi, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-7_Part_1-199310010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As anesthesiologists who are constantly faced with the challenge of providing anesthesia for pregnant women, we found the recent review [1] timely and informative. We feel, however, that the section dealing with the risk for aspiration during anesthesia is misleading.Aspiration of stomach contents during anesthesia is a major cause of morbidity and mortality in pregnant women. The authors conclude that antacids and histamine-2 blockers are the cornerstone of therapy for the prevention of aspiration pneumonitis.Clinicians should be cautioned that not all antacids are appropriate in this situation. The use of insoluble antacids is contraindicated [2]. ...References1. Baron TH, Ramirez B, Richter JE. Gastrointestinal motility disorders during pregnancy. Ann Intern Med. 1993; 118:366-75. Google Scholar2. Barash PG, ed. Clinical Anesthesia. Philadelphia: J.B. Lippincott; 1992:625. Google Scholar3. Shnider SM, Levinson G, eds. Anesthesia for Obstetrics. Baltimore: Williams & Wilkins; 1993:421-2. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGastroesophageal reflux disease during pregnancy 1 October 1993Volume 119, Issue 7_Part_1Page: 635KeywordsAnesthesiaDrugsMorbidityMortalityParticulatesPneumonitisPregnancySodiumStomachSurgery Issue Published: 1 October 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cost-Utility Analyses of Cognitive-Behavioural Therapy of Depression: A Systematic Review
Authors: Christian Brettschneider, Helei Djadran, Martin Härter, Bernd Löwe, Steffi Riedel-Heller, Hans-Helmut König
Journal: Psychotherapy and Psychosomatics (2014)

Background: Major depressive disorder (MDD) causes a massive disease burden worldwide. Cognitive behavioural therapy (CBT) is an important treatment approach for depression. Cost-utility analysis (CUA) is a method to support decisions on efficient allocation of resources in health policy. The objective of our study was to systematically review CUA of CBT in the treatment of patients suffering from MDD. Methods: We conducted a systematic literature search in Medline, Embase, PsycINFO and National Health Service Economic Evaluation Database (NHS EED) to identify CUA of CBT for MDD. Cost data were inflated to the year 2011 and converted into USD using purchasing power parities (USD PPP) to ensure comparability of the data. Quality assessment of CUA was performed. Results: Twenty-two studies were included in this systematic review. No study employed a time horizon of more than 5 years. In most studies, individual and group CBT as well as CBT for maintenance showed acceptable incremental cost-utility ratios (<50,000 USD PPP/quality-adjusted life year). The CUA results of CBT for children and adolescents and of computerized CBT were inconsistent. Discussion: We found consistent evidence that individualized CBT is cost-effective from the perspective of a third-party payer for short-term treatment and for relapse prevention of MDD in the adult population.
Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-γ–mediated pathways
Authors: Jianguo Liu, Xiuqin Guan, Xiaojing Ma
Journal: The Journal of Experimental Medicine (2007)

Interleukin (IL)-27 is the newest member of the IL-12 family of heterodimeric cytokines composed of the Epstein-Barr virus–induced gene 3 and p28 chains. IL-27 not only plays an important role in the regulation of differentiation of naive T helper cells but also possesses antiinflammatory properties. IL-27 is an early product of activated monocytes/macrophages and dendritic cells. However, the mechanisms whereby inflammatory signals stimulate IL-27 production have not been explored. In this study, we investigated the transcriptional regulation of the mouse IL-27 p28 gene in macrophages in response to lipopolysaccharide (LPS) and interferon (IFN)-γ. We found that LPS-stimulated p28 production was completely dependent on the Toll-like receptor 4/myeloid differentiation factor 88 (MyD88)–mediated pathway but only partially dependent on nuclear factor κB c-Rel. IFN-γ–induced p28 production/secretion was also partially dependent on MyD88 but independent of c-Rel. We then cloned the mouse p28 gene promoter and mapped its multiple transcription initiation sites. Furthermore, we identified critical promoter elements that mediate the inductive effects of LPS and IFN-γ, separately and synergistically, on p28 gene transcription in a c-Rel– and interferon regulatory factor 1–dependent manner, respectively.
Increase of lymphocytes with Fc receptors for IgE in patients with allergic rhinitis during the grass pollen season.
Authors: H L Spiegelberg, R A Simon
Journal: Journal of Clinical Investigation (1981)

Peripheral blood lymphocytes from 10 nonallergic donors and 7 patients suffering from seasonal allergic rhinitis and receiving desensitization therapy were analyzed by rosette assays for Fc receptors for IgE (Fc epsilon R) and IgG (Fc gamma R) before, during and after the grass pollen season. Six of seven patients had moderately elevated IgE levels (330 +/- 268 IU/ml), all had high titers of skin sensitizing antibodies to grass pollens and serum IgE antibodies as measured by radio-allergosorbent tests (RAST). Seven of the nonallergic donors had 2-30 IU/ml IgE and negative RAST, whereas three had 91-267 IU/ml IgE and two were RAST positive to the grass pollens. In March, when the patients were asymptomatic, the mean +/-SD of the Fc epsilon R+ lymphocytes did not significantly differ from the nonallergic control group: nonallergic Fc epsilon R+ 1.2 +/- 0.9% (29 +/- 20/,mm3), allergic Fc epsilon R+ 2.0 +/- 3.1% (48 +/- 52/mm3). In contrast, during the grass pollen season in May and June, when the patients developed symptoms of allergic rhinitis, they had significantly (P less than 0.01) more Fc epsilon R+ lymphocytes than the controls: nonallergic Fc epsilon R+ 1.7 +/- 1.9% (40 +/- 46/mm3), allergic Fc epsilon R+ 4.7 +/- 1.2% (134 +/- 69/mm3). In the postpollen period, August-October, most of the patients again had low numbers of Fc epsilon R+ lymphocytes: nonallergic Fc epsilon R+ 1.4 +/- 0.9% (26 +/- 13/mm3), allergic Fc epsilon R+ 2.1 +/- 1.9% (62 +/- 82/mm3). The nonallergic control donors with elevated IgE levels and positive RAST always had low numbers of Fc epsilon R+ lymphocytes. In contrast, two other nonallergic donors, who had a 2-7 IU/ml IgE and negative RAST, showed significant increases of Fc epsilon R+ lymphocytes over several weeks during the grass pollen season. No statistically significant changes in Fc gamma R+ lymphocytes occurred in both nonallergic and allergic donors. The total and specific IgE serum levels did not vary much in the nonallergic donors and patients during the period of study and any changes that did occur did not correlate with the changes in Fc epsilon R+ lymphocytes. The data demonstrate that Fc epsilon R+ peripheral blood lymphocytes increase in allergic patients during natural antigen exposure and active disease in the absence of measurable increases of total and specific serum IgE. Because two nonallergic control donors also had temporary increases of Fc epsilon R+ lymphocytes, an increase of peripheral blood Fc epsilon R+ lymphocytes may be a sensitive indicator of an ongoing IgE immune response.
Systemic antibiotics in the treatment of periodontitis
Authors: Magda Feres, Luciene C. Figueiredo, Geisla M. Silva Soares, Marcelo Faveri
Journal: Periodontology 2000 (2014)

Abstract Despite the fact that several clinical studies have shown additional benefits when certain systemic antibiotics are used as adjuncts to periodontal treatment, clear guidelines for the use of these agents in the clinical practice are not yet available. Basic questions concerning the use of systemic antibiotics to treat periodontitis remain unanswered, such as: which drug(s) should be used; which patients would most benefit from treatment; which are the most effective protocols (i.e. doses and durations); and in which phase of the mechanical therapy should the drug(s) be administered? Although not all of those questions have been directly addressed by controlled randomized clinical trials, recent concepts related to the ecology of periodontal diseases, as well as the major advances in laboratory and clinical research methods that have occurred in the past decade, have significantly broadened our knowledge in this field. This article endeavored to provide a ‘state of the art’ overview on the use of systemic antibiotics in the treatment of periodontitis, based on the most recent literature on the topic as well as on a compilation of data from studies conducted at the Center of Clinical Trials at Guarulhos University (São Paulo, Brazil) from 2002 to 2012.