tbuckley/cabot-search huggingface dataset:
High-Level Protein Secretion into Blood Circulation after Electric Pulse-Mediated Gene Transfer into Skeletal Muscle
Authors: Mickaël Bettan, Florence Emmanuel, Raphaël Darteil, Jean-Michel Caillaud, Fabienne Soubrier, Pia Delaere, Didier Branelec, Abderrahim Mahfoudi, Nicolas Duverger, Daniel Scherman
Journal: Molecular Therapy (2000)

Numerous diseases are linked to the absence or insufficient concentration of a specific plasma protein. Gene transfer is an appealing strategy for correction of such diseases. We report high and sustained plasma secretion of human secreted alkaline phosphatase and of human Factor IX by skeletal muscle of mice. This was obtained by delivering square-wave unipolar electric pulses of low field strength (200 V/cm) and long duration (20 ms) to skeletal muscle previously injected with plasmid DNA encoding for the secreted protein. This intramuscular electrotransfer method allows 30- to 150-fold increase in reporter protein secretion, compared to simple plasmid DNA injection. This increase allows one to obtain values of up to 2200 ng/ml of a reporter circulating protein. Moreover, this high level of secretion remains stable for several months. Numerous diseases are linked to the absence or insufficient concentration of a specific plasma protein. Gene transfer is an appealing strategy for correction of such diseases. We report high and sustained plasma secretion of human secreted alkaline phosphatase and of human Factor IX by skeletal muscle of mice. This was obtained by delivering square-wave unipolar electric pulses of low field strength (200 V/cm) and long duration (20 ms) to skeletal muscle previously injected with plasmid DNA encoding for the secreted protein. This intramuscular electrotransfer method allows 30- to 150-fold increase in reporter protein secretion, compared to simple plasmid DNA injection. This increase allows one to obtain values of up to 2200 ng/ml of a reporter circulating protein. Moreover, this high level of secretion remains stable for several months.
BMP-7 attenuates left ventricular remodelling under pressure overload and facilitates reverse remodelling and functional recovery
Authors: David Merino, Ana V. Villar, Raquel García, Mónica Tramullas, Luis Ruiz, Catalina Ribas, Sofía Cabezudo, Juan Francisco Nistal, María A. Hurlé
Journal: Cardiovascular Research (2016)

TGF-β regulates tissue fibrosis: TGF-β promotes fibrosis, whereas bone morphogenetic protein (BMP)-7 is antifibrotic. To demonstrate that (i) left ventricular (LV) remodelling after pressure overload is associated with disequilibrium in the signalling mediated by these cytokines, and (ii) BMP-7 exerts beneficial effects on LV remodelling and reverse remodelling. We studied patients with aortic stenosis (AS) and mice subjected to transverse aortic constriction (TAC) and TAC release (de-TAC). LV morphology and function were assessed by echocardiography. LV biopsies were analysed by qPCR, immunoblotting, and histology. Pressure overload reduced BMP-7 and pSmad1/5/8 and increased TGF-β and pSmad2/3 in AS patients and TAC mice. BMP-7 correlated inversely with collagen, fibronectin, and β-MHC expressions, and with hypertrophy and diastolic dysfunction, and directly with the systolic function. Multiple linear regression disclosed BMP-7 and TGF-β as hypertrophy predictors, negative and positive, respectively. BMP-7 prevented TGF-β-elicited hypertrophic program in cardiomyocytes, and Col1A1 promoter activity in NIH-3T3 fibroblasts. The treatment of TAC mice with rBMP-7 attenuated the development of structural damage and dysfunction, and halted ongoing remodelling. The reverse remodelling after pressure overload release was facilitated by rBMP-7, and hampered by disrupting BMP-7 function using a neutralizing antibody or genetic deletion. The disequilibrium between BMP-7 and TGF-β signals plays a relevant role in the LV remodelling response to haemodynamic stress in TAC mice and AS patients. Our observations may provide new important insights aimed at developing novel therapies designed to prevent, halt, or reverse LV pathological remodelling in pressure overload cardiomyopathy.
U.S., Mongolia Meetings Held; Liver Cancer Discussed
Authors: M. E. Newman
Journal: JNCI Journal of the National Cancer Institute (1991)

U.S., Mongolia Meetings Held; Liver Cancer Discussed Get access Michael E. Newman Michael E. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 10, 15 May 1991, Pages 667–668, https://doi.org/10.1093/jnci/83.10.667 Published: 15 May 1991
Antibody Responses in Serum and Nasal Secretions of Children Immunized with Inactivated and Attenuated Measles-Virus Vaccines
Authors: Joseph A. Bellanti, Rosvida L. Sanga, Barbara Klutinis, Brenda Brandt, Malcolm S. Artenstein
Journal: New England Journal of Medicine (1969)

In 24 children immunized with inactivated or attenuated measles-virus vaccines, responses of serum antibody (characterized by density-gradient ultracentrifugation and radioimmunodiffusion studies) were comparable both in peak titers and in immunoglobulin contribution. In eight of nine children immunized with attenuated measles-virus vaccine nasal antibody associated primarily with the γA and less often with γG immunoglobulins developed; nasal antibody was detected in only three of seven immunized with inactivated measles-virus vaccine, and in these both γA and γG activities were observed. Of eight children with pre-existing serum antibody, six had nasal antibody in the preimmunization specimens. The differences in ability of these vaccines to stimulate local respiratory-tract antibody may in part explain the greater clinical effectiveness of the attenuated vaccine as well as the occurrence of altered reactivity of the host who received inactivated vaccine.
Invasive Group A Streptococcal Infections in Ontario, Canada
Authors: H. Dele Davies, Allison McGeer, Benjamin Schwartz, Karen Green, Darlene Cann, Andrew E. Simor, Donald E. Low
Journal: New England Journal of Medicine (1996)

Several reports suggest that the incidence of invasive group A streptococcal infections, including streptococcal toxic shock syndrome and necrotizing fasciitis, is increasing.
Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial
Authors: Andrew W Hitchings, Dilys Lai, Paul W Jones, Emma H Baker
Journal: Thorax (2016)

<h3>Background</h3> Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. <h3>Methods</h3> This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. <h3>Results</h3> 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. <h3>Conclusion</h3> Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. <h3>Trial registration number</h3> ISRCTN66148745 and NCT01247870.
PTU-221 Dysphagia in a DGH: is there histological correlation of the visual diagnosis?
Authors: K Axe, C Ch'ng, J Nagaraj
Journal: Gut (2012)

<h3>Introduction</h3> Dysphagia is a clinically important indication of malignancy; as well as a symptom of Oesophagitis, Barrett9s oesophagus (BO), and peptic strictures; all of which should be easily recognised at biopsy. Dysphagia in younger patients9 may indicate Eosinophilic Oesophagitis (EO), which may only be visible on histology. The aim of this study was to review the demographics of patients undergoing endoscopy and if there was histological and visual correlation to help guide our investigation of dysphagia. <h3>Methods</h3> A retrospective study including dysphagic patients attending endoscopy at Singleton or Morriston hospital between 1 January 2010 and 31 October 2011. Patients were reviewed to identify demographics, endoscopic findings and correlation between visual and histological diagnosis. Where biopsies were indicated in the endoscopy report results were cross matched with the histology results. Hiatus hernia was considered normal and unspecified mass was considered to represent a visual diagnosis of malignancy unless otherwise stated. Patients undergoing more than one procedure had each procedure entered as a separate data set. <h3>Results</h3> 694 patients (334 male, 340 female), median age 67 (range 21–99), 77% patients over 50. Endoscopy was visually normal in 45%, the commonest visual abnormalities were Oesophagitis (18%) and malignancy (13%). 23% of patients had biopsies. Suspected malignancy or BO were most likely to have biopsies taken (65% and 64% respectively), 9% visually normal endoscopies were biopsied. 83% (49 cases) with suspected malignancy had histological correlation, 17% (11 cases) had BO or Oesophagitis. Three patients were found to have malignancy where the visual diagnosis had been Oesophagitis or benign stricture. Both BO and Oesophagitis had &gt;80% correlation visually and histologically. Six cases of EO were found, all were visually normal. One suspected case was seen at endoscopy, this was histologically normal. <h3>Conclusion</h3> There was generally good correlation between visual and endoscopic diagnosis, particularly in malignancy, however biopsy number was lower than expected. Failure to biopsy may lead to missed diagnosis of cancer or dysplasia. All cases of EO in adults had normal endoscopy, few patients with dysphagia and normal endoscopy had biopsies taken. EO may be commoner than suspected, true rates are unknown and a high index of suspicion is needed. We should carry out more endoscopies on younger patients with symptoms in keeping with EO and biopsy normal oesophagus in cases where this diagnosis is suspected. <h3>Competing interests</h3> None declared.
THE RAILROAD TRACK SIGN: INTENSE GASTRIC WALL UPTAKE ON TC-99M SESTAMIBI SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY MYOCARDIAL PERFUSION IMAGING IN PATIENTS WITH END-STAGE LIVER DISEASE
Authors: Vedant Arun Gupta, Yuri Boyechko, M. Elizabeth Oates, Vincent Sorrell
Journal: Journal of the American College of Cardiology (2015)
Sentinel Node breast Lymphatic Mapping
Authors: L K Dunnwald, J F Eary, D A Mankoff, D Byrd, B Anderson, R Yeung, R Moe
Journal: Clinical Nuclear Medicine (1999)

Dunnwald, L; Eary, J F; Mankoff, D A; Byrd, D; Anderson, B; Yeung, R; Moe, R Author Information
Abstract 1295: Regulation of PAX2 activity by estradiol in breast cancer cells
Authors: David Beauchemin, Catherine Lacombe, Céline Van Themsche
Journal: Cancer Research (2012)

Abstract Most breast cancer deaths arise from tumour cells ability to produce distant metastases. Among breast tumour subtypes, luminal A tumours, which express the highest levels of estrogen receptor alpha, are associated with the poorest metastatic phenotype and with longest relapse-free survival. Usually active during embryogenesis, PAX2, a homeobox transcription factor, is of a particular interest in this context. It is preferentially activated in luminal A tumours in vivo and it was shown to downregulate the expression of ERBB2 (erythroblastic leukemia viral oncogene homolog 2, HER-2/neu), a well-documented proinvasive and pro-metastastic gene, in these cells in response to estradiol in vitro. However, the ability of estradiol to regulate PAX2 activity and ERBB2 expression in non-luminal breast cancer cells, and the intracellular mechanisms involved in estradiol-induced PAX2 activity in breast cancer cells, have not been investigated. Objective: The objective of our work was to compare the impact of estradiol exposure on PAX2 activation in luminal and non-luminal breast cancer cells, and to determine the molecular mechanisms mediating estradiol-induced activation in breast cancer cells. Hypothesis: Estradiol would induce PAX2 activity in breast cancer cells of the luminal subtype only, in an estradiol receptor alpha-dependent manner. Results: Basal PAX2 activity was higher in cell lines from luminal compared to non-luminal subtype. Activation of PAX2 by estradiol, as assessed by measuring PAX2 phosphorylation on serine 393 residue and ERBB2 expression, was selectively achieved in breast cancer cell lines of the luminal subtype. This process was blocked by estrogen receptor alpha antagonist ICI 182780. Conclusion: PAX2 activation by estradiol is selectively achieved in breast cancer cells of the luminal subtype, via ERα. We are currently investigating intracellular signaling pathways downstream of estrogen receptor alpha which could mediate estradiol-induced activation of PAX2 in luminal breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1295. doi:1538-7445.AM2012-1295
Trends in Medical Education and Health Services
Authors: Richard M. Magraw
Journal: New England Journal of Medicine (1971)

Abstract The selection of careers from among available specialties partly depends on an assessment of trends in medicine. More obviously than other specialties those providing primary care (e.g., family practice) are "system-defined" — i.e., they are shaped and made real by the needs of the present system of care. Students now selecting careers in family medicine are acting on current assumptions about the medical-care system of the future, although opinion in academic medicine and among medical practitioners remains divided about these issues. This analysis of factors acting to shape the system of medical care indicates a slow, ponderous and steady movement toward emphasis on primary care, family medicine and family practice. That movement may be expected to accelerate during the next two or three years — a time that will be critical in determining whether the function of primary care and family medicine will be fully professionalized and built into the evolving American medical system.
You say you want a revolution?
Authors: Mark Alicke
Journal: Behavioral and Brain Sciences (2012)

Abstract I argue that Dixon et al. fail to maintain a careful distinction between the negative evaluation definition of “prejudice” and the implications of this definition for correcting the social ills that prejudice engenders. I also argue that they adduce little evidence to suggest that if prejudice were diminished, commensurate reductions in discrimination would not follow.
New 55.6m European project will use stem cells to increase understanding of diseases
Authors: N. Hawkes
Journal: BMJ (2012)

A five year collaborative project costing €55.6m (£45m; $72.7m) has been launched to use stem cells to increase understanding of diseases and devise better ways to treat them. The project, called Stembanc, brings together academic centres across Europe with drug companies to create “the patient in a dish”—cultures of cells grown from stem cells taken from patients and used as assays for new drug treatments.

The approach will take skin and blood cells from 500 patients and use techniques that won the Japanese clinician Shinya Yamanaka a share of this year’s Nobel prize for Medicine.1 The cells will then be restored to their precursor stem cells, the so called induced pluripotent stem (IPS) cells that have the capacity …
Intrathecal Baclofen for Severe Spinal Spasticity
Authors: Richard D. Penn, Suzanne M. Savoy, Daniel Corcos, Mark Latash, Gerald Gottlieb, Barbara Parke, Jeffrey S. Kroin
Journal: New England Journal of Medicine (1989)

We studied the effect of the intrathecal infusion of baclofen, an agonist of gamma-aminobutyric acid, on abnormal muscle tone and spasms associated with spinal spasticity, in a randomized double-blind crossover study. Twenty patients with spinal spasticity caused by multiple sclerosis or spinal-cord injury who had had no response to treatment with oral baclofen received an intrathecal infusion of baclofen or saline for three days. The infusions were administered by means of a programmable pump implanted in the lumbar subarachnoid space. Muscle tone decreased in all 20 patients (mean [±SD] Ashworth score for rigidity, from 4.0±1.0 to 1.2±0.4; P<0.0001), and spasms were decreased in 18 of the 19 patients who had spasms (mean [±SD] score for spasm frequency, from 3.3± 1.2 to 0.4±0.8; P<0.0005). Tests for motor function, neurologic examination, and assessments by the patients correctly indicated when baclofen was being infused in all cases. All patients were then entered in an open long-term trial of continuous infusion of intrathecal baclofen. During a mean follow-up period of 19.2 months (range, 10 to 33), muscle tone has been maintained within the normal range (mean Ashworth score, 1.0±0.1) and spasms have been reduced to a level that does not interfere with activities of daily living (mean spasm score, 0.3±0.6). No drowsiness or confusion occurred, one pump failed, and two catheters became dislodged and had to be replaced. No infections were observed. Our observations suggest that intrathecal baclofen is an effective long-term treatment for spinal spasticity that has not responded to oral baclofen. (N Engl J Med 1989; 320:1517–21.)
Abstract 153: Reduction of microRNAs miR-15a and miR-16-1 in odontogenic keratocyst
Authors: Ricardo S. Gomez, Marina G. Diniz, Carolina C. Gomes, Wagner H. Castro, Andre Luiz S. Guimarães, Alfredo Maurício B. de Paula
Journal: Cancer Research (2011)

Abstract Odontogenic keratocyst (OKC) is a benign destructive recurrent odontogenic cystic neoplasm. MicroRNAs (miRNAs) miR-15a and miR-16-1 are small non-protein coding RNAs that function as negative regulators of the anti-apoptotic gene BCL-2 at the post-transcriptional level. Increased immunoexpression of BCL-2 protein is reported in OKC. The purpose of the present study was to investigate whether miR-15a and miR-16-1 transcription is altered in OKC and if it is associated with BCL-2 expression in such lesions. Compared to dental follicles, we found higher BCL-2 mRNA expression and immunoreactivity in OKC. Our findings also showed that miR-15a and/or miR-16-1 are downregulated in the majority of OKC samples (24/28). Furthermore, in all five OKC paired samples (primary and marsupialized lesions) investigated there was an increase in the expression of miR-15a after marsupialization. Our results suggest that OKC neoplastic cells present an anti-apoptotic profile to which lower miR-16-15a expression might contribute. Additionally, our findings strongly suggest that marsupialization reduces BCL-2 expression in the OKC and this downregulation may result from microRNA post-transcriptional activity, even though this cause-effect relationship remains to be proved. This study was supported by FAPEMIG and CAPES, Brazil. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 153. doi:10.1158/1538-7445.AM2011-153
Transmission of Hepatitis C Virus by a Cardiac Surgeon
Authors: Juan I. Esteban, Jordi Gómez, María Martell, Beatriz Cabot, Josep Quer, Joan Camps, Antonio González, Teresa Otero, Andrés Moya, Rafael Esteban, Jaime Guardia
Journal: New England Journal of Medicine (1996)

In the course of a study conducted from 1992 through 1994 of the efficacy of screening blood donors for antibodies to hepatitis C virus (HCV), we found that two patients had acquired hepatitis C after cardiac surgery, with the transmission apparently unrelated to blood transfusions. Because their surgeon had chronic hepatitis C, we sought to determine whether he was transmitting the virus to his patients.
Contralateral Breast Cancer in BRCA1/2 Mutation Carriers: Risk Assessment by Age at Diagnosis of the First Primary Breast Cancer.
Authors: M. Hooning, B. Heemskerk-Gerritsen, A. Jager, M. Collee, A. van den Ouweland, M. Menke - Pluymers, B. van Geel, L. van Doorn, M. Tilanus - Linthorst, C. Bartels, C. Seynaeve
Journal: Cancer Research (2009)

Abstract Purpose Age at diagnosis of the first breast cancer is a known predictive factor of the risk of contralateral breast cancer (CBC) in BRCA1/2 mutation carriers. However, accurate risk estimates for different age subgroups are scarce.Methods We studied the risk of CBC in 560 women with a primary breast cancer (PBC) from families with a proven BRCA1 or BRCA2 mutation in relation to the age at diagnosis of the first PBC, taking into account history of oophorectomy. Time at risk was the period between diagnosis of the first PBC and date of contralateral breast cancer, contralateral mastectomy, metastatic disease, death or last follow-up. Oophorectomy was treated as a time-dependent covariate. Patients with bilateral breast cancer diagnosed before the first visit at the family cancer clinic were excluded.Results We observed 96 CBCs in 423 BRCA1 mutation carriers and 21 cases in 137 BRCA2 mutation carriers. Actuarial risk of CBC at 5, 10 and 15 years was 14%, 34% and 39%, respectively, for BRCA1-, and 13%, 22% and 27%, respectively, for BRCA2 mutation carriers. For BRCA1 carriers 10-year actuarial risk of CBC was 54% for women with a PBC ≤ 30 years, 39% for the group with PBC between 31-40 years, 26% for the 41-50 group and 17% for those with PBC &amp;gt; 50 years. In BRCA2 carriers 10-year risk of CBC was 28% for women with a PBC ≤ 40 years, 19% for the 41-50 group and 10% for those with PBC &amp;gt; 50 years. For BRCA1 carriers who had an oophorectomy, 10-year risk of CBC was 33% and 26%, respectively, for those with PBC younger and older than 40 years, against 44% and 24% in women who had no such treatment. In BRCA2 carriers with a history of oophorectomy 10-year risk of CBC was 21% and 14%, respectively, for those with PBC younger and older than 40 years, while the risk was 29% and 17%, respectively, in women without oophorectomy. Effect of adjuvant therapy is being analyzed and will be presented at the meeting.Conclusions The availability of risk estimates of CBC by more detailed age groups at PBC is a helpful tool in the counselling process concerning screening and/or preventive surgery for breast cancer patients with a BRCA1 or BRCA2 mutation. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 903.
P727Nucleotide-binding oligomerization domain-containing protein 1-signaling is upregulated in hearts from type 2 diabetic mice
Authors: S Gonzalez-Ramos, P Prieto, G Benito, V Terron, L Bosca, M Fernandez-Velasco
Journal: Cardiovascular Research (2014)

Introduction: Type 2 diabetes is a complex pathology that involves deregulated lipid metabolism, insulin resistance together with a chronic inflammatory state. Nucleotide-binding oligomerization domain-containing protein (NOD) 1 is an innate immune system receptor that can participate in the pathogenesis of diabetes in hepatic and adipose tissues.