tbuckley/cabot-search huggingface dataset:
Genetic deletion of the GATA1‐regulated protein α‐synuclein reduces oxidative stress and nitric oxide synthase levels in mature erythrocytes
Authors: Raffaele Renella, Julia S. Schlehe, Dennis J. Selkoe, David A. Williams, Matthew J. LaVoie
Journal: American Journal of Hematology (2014)

α-Synuclein is highly expressed in neural tissue and during erythropoiesis, where the key erythroid regulator GATA1 has been found to modulate its expression. While specific α-synuclein (SNCA) mutations are known to cause autosomal dominant familial Parkinson's disease, its wild-type function remains under debate. To investigate the role of α-synuclein in murine hematopoiesis and erythropoiesis, we utilized Snca knock-out mice and analyzed erythroid compartments for maturation defects, in vivo erythrocyte survival, and erythrocyte-based reactive oxygen species (ROS) and nitric oxide synthase (NOS) levels. Our findings show that while bone marrow and spleen erythropoiesis and peripheral blood erythrocyte survival in Snca(-/-) mice was comparable to controls, the levels of ROS and of NOS-2 were significantly decreased in mature erythrocytes in these animals. These results indicate a role for α-synuclein in regulating oxidative stress in erythrocytes in vivo and could open new avenues for the investigation of its function in non-neural tissue.
&lt;italic&gt;In Vivo&lt;/italic&gt; Oxidation of Glucose-1-&lt;sup&gt;14&lt;/sup&gt;C and Glucose-6-&lt;sup&gt;14&lt;/sup&gt;C in Mice With 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hans R. Burki, George T. Okita
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article In Vivo Oxidation of Glucose-1-14C and Glucose-6-14C in Mice With 7,12-Dimethylbenz[a]anthracene-Induced Tumors Get access Hans R. Burki, Hans R. Burki Northwestern University Medical School, Department of Pharmacology, Chicago, Illinois 60611 Search for other works by this author on: Oxford Academic PubMed Google Scholar George T. Okita George T. Okita Northwestern University Medical School, Department of Pharmacology, Chicago, Illinois 60611 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 43, Issue 3, September 1969, Pages 643–651, https://doi.org/10.1093/jnci/43.3.643 Published: 01 September 1969 Article history Received: 07 April 1969 Accepted: 20 May 1969 Published: 01 September 1969
Surveillance endoscopy is associated with improved outcomes of oesophageal adenocarcinoma detected in patients with Barrett's oesophagus
Authors: Hashem B El-Serag, Aanand D Naik, Zhigang Duan, Mohammad Shakhatreh, Ashley Helm, Amita Pathak, Marilyn Hinojosa-Lindsey, Jason Hou, Theresa Nguyen, John Chen, Jennifer R Kramer
Journal: Gut (2015)

The effectiveness of surveillance endoscopy in patients with Barrett's oesophagus (BE) for reducing oesophageal adenocarcinoma (EAC)-related mortality in patients with BE is unclear.This is a cohort study of patients with BE diagnosed in the National Veterans Affairs hospitals during 2004-2009 excluding those with conditions that affect overall survival. We identified those diagnosed with EAC after BE diagnosis through 2011 and conducted chart reviews to identify BE surveillance programme, and indication for EAC diagnosis, verify diagnosis, stage, therapy and cause of death. We examined the association between surveillance indication for EAC diagnosis with or without surveillance programme and EAC stage and treatment receipt in logistic regression models, and with time to death or cancer-related death using a Cox proportional hazards regression model.Among 29 536 patients with BE, 424 patients developed EAC during a mean follow-up of 5.0 years. A total of 209 (49.3%) patients with EAC were in BE surveillance programme and were diagnosed as a result of surveillance endoscopy. These patients were more likely to be diagnosed at an early stage (stage 0 or 1: 74.7% vs 56.2, p<0.001), survived longer (median 3.2 vs 2.3 years; p<0.001) and have lower cancer-related mortality (34.0% vs 54.0%, p<0.0001) and had a trend to receive oesophagectomy (51.2% vs 42.3%; p=0.07) than 215 patients diagnosed by non-BE surveillance endoscopy (17.2% of whom were BE surveillance failure). BE surveillance endoscopy was associated with a decreased risk of cancer-related death (HR 0.47, 0.35 to 0.64), which was largely explained by the early stage of EAC at the time of diagnosis. Similarly, the adjusted mortality for patients with cancer in a prior surveillance programme for overall death was 0.63 (0.47 to 0.84) compared with patients with cancer not in a surveillance programme.Surveillance endoscopy among patients with BE is associated with significantly better EAC outcomes including cancer-related mortality compared with other non-surveillance endoscopy.
Prognostic value of red cell distribution width in patients with pulmonary embolism
Authors: Savas Ozsu, Yasin Abul, Selda Gunaydin, Asim Orem, Tevfik Ozlu
Journal: European Respiratory Journal (2012)

Elevated red blood cell distribution width (RDW) has been associated with adverse outcomes of heart failure and pulmonary hypertension.We speculated that a higher RDW would be independently associated with poor clinical outcomes in pulmonary embolism(PE) patients.  A total of 702 consecutive patients with acute PE were evaluated. We collected each patient 9 s base-line characteristics including RDW. The primary end-point was all-cause in hospital mortality. Receiver operating characteristic (ROC) analysis was performed to determine the optimal RDW cut-off levels with regard to prognosis. We used logistic regression to assess the association between RDW at the time of presentation and inhospital mortality after adjusting for patient (age, clinical and laboratory variables) factors.  There was a graded increase in mortality rate with each RDW quartiles: 5.8% in quartile I ( 16.3%) (p for trends =15% and the negative predictive value was 93% for mortality. In multivariate regression analysis, RDW remained associated with an increased odds of death.  RDW levels may provide a potential marker to predict outcome in PE patients.
Abstract 142: Defining the Non-Myocyte Compartment is Key for Enhanced Maturation of Human Engineered Heart Muscle
Authors: Malte Tiburcy, James E Hudson, Dirk Ziebolz, Wolfram H Zimmermann
Journal: Circulation Research (2014)

Background: Tissue engineering of heart muscle from human pluripotent stem cells holds great potential for in vitro studies, disease modeling, and cardiac replacement therapy. A number of variables may however affect maturation and function of human cardiomyocytes (CM) in tissue engineered heart muscle (EHM). Here, we hypothesized that defined non-myocyte (NM) populations support structural and functional maturation of EHM. Methods and Results: To investigate the role of non-myocytes (NM) for heart muscle assembly in vitro we generated EHM from purified CM (93±1.5% actinin+) and a mixture of CM and NM (70/30%). Notably, only the NM-supplemented EHM generated measurable forces (0.8±0.1 mN, n=9) with anisotropically aligned cardiomyocytes. Depending on pluripotent stem cell line and differentiation protocol the NM compartment may vary considerably. To further define the influence of the NM compartment we generated EHM from HES2-derived CM with undefined NM, i.e the NM typically derived during cardiac differentiation, and defined NM (fibroblasts). Defined EHM were more mature with higher forces and lower variability between experimental series (defined: 9.8±0.9 nN/CM, undefined: 4.7±1.4 nN/CM, n=10/9), higher EC50 for calcium, and enhanced inotropic response to isoprenaline despite comparable CM:NM composition of 1:1. Increased actinin protein per CM, a reduction of MLC2V/2A double positive CM, and evidence of CM cycle withdrawal indicated enhanced ventricular maturation in defined EHM. Next, we tested whether defining cell composition and NM in iPS-derived EHM will yield a comparable functional phenotype to HES2-EHM. In agreement with the above data, defined iPS-EHM displayed advanced functional maturation with high specific forces, comparable calcium EC50, and inotropic response to isoprenaline. Summary and Conclusions: Here we demonstrate that defining the NM compartment is essential for optimized human heart muscle formation and maturation in vitro. Moreover, our data provide (1) evidence for the applicability of EHM in modelling of heart muscle development and (2) a strong rationale for the need to define CM and NM compartments in tissue engineered myocardium to reduce variability in applications such as disease modelling.
The journey to severe obstructive lung disease - Retrospective study of FEV1 decline
Authors: Rupert Jones, Matthew Masoli, Adam Qureshi, Helen Grover, Gemma Hayes, Fawzi Ali, David Jones
Journal: European Respiratory Journal (2012)

Aims 

To assess the rate of decline of FEVI over time in patients with GOLD stage 3- 4 COPD and compare the rate of decline in non smokers and smokers.

Methods 

The primary outcome was the rate of decline of FEV1 /year in current smokers versus non smokers; secondary outcomes included the rate of decline in FEV1 at different stages of airflow obstruction.

In a retrospective case series, we included patients with a primary diagnosis of COPD, GOLD stage 3- 4 under regular review with 3 years spirometry data performed in the respiratory clinic using standard methods. The sample was divided into non- smokers, persistent smokers, and intermittent quitters.

Results 

Data was available for 95 patients range 3-23 years.

The rate of decline in smokers was significantly higher than non-smokers. The mean (SD) decline in FEV1 (ml/yr) was faster in earlier stages in GOLD2 53.2 (16.7); GOLD3 32.0 (29.7) and GOLD4 5.9 (7.2). In the overall sample the line of best fit of FEV1 over time was exponential.

View this table:

Rate if decline in FEV1 in ml/year





The rates of decline (mean (SD)) in non-smokers GOLD3 was 33.9 (35.3) and GOLD4 17.3 (51.3) and for smokers GOLD3 = 42.7 (34.5) and GOLD4 = 25.3 (N/A).

Conclusion 

Even in late stages the decline in FEV1 is faster in smokers than intermittent quitters who declined faster than non smokers. Unlike the Fletcher Peto diagram we found that the decline in FEV1 was faster in earlier than later stages. The benefits of quitting diminish as the disease progresses. To minimise lung damage it is essential identify people in early stages and for them to stop smoking immediately.
Relation of body mass index to asthma and atopy in children: the National Health and Nutrition Examination Study III
Authors: E von Mutius, J Schwartz, L M Neas, D Dockery, S T Weiss
Journal: Thorax (2001)

<h3>BACKGROUND</h3> An increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. <h3>METHODS</h3> Children aged 4–17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m<sup>2</sup> and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. <h3>RESULTS</h3> The prevalence of asthma (8.7% <i>v</i> 9.3%<i>v</i> 10.3% <i>v</i>14.9%, p=0.0001) and atopy (48.6% <i>v</i> 50.5%<i>v</i> 53.0% <i>v</i>53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. <h3>CONCLUSIONS</h3> The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.
The Trans-Pacific Partnership Agreement and Implications for Access to Essential Medicines
Authors: Jing Luo, Aaron S. Kesselheim
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Efficiency of Antitumor Screening Relative to Activity Criteria
Authors: K Paull, L Hodes, R M Simon
Journal: JNCI Journal of the National Cancer Institute (1986)

Well over 100,000 compounds have been screened by the National Cancer Institute (NCI) in mouse leukemia P388 in the search for new leads toward antineoplastic agents. The protocol for screening requires confirmation testing of compounds showing initial activity. By activity criteria being varied for initial and confirmation testing, it is possible to improve the efficiency of screening. The experimental variability of P388 screening was first determined by analysis of outcomes from 90 tests on each of 21 compounds of varied activity. By application of these results to NCI P388 data for 31,428 compounds adequately tested on a daily times five schedule, the consequences of using different activity thresholds were estimated. The results here may apply to those of other similar large-scale screening programs.
Medicine by numbers
Authors: Theodora Bloom
Journal: BMJ (2015)

What’s the evidence that any of the 150 000 health apps available in Europe actually work? Not much, says Stephen Armstrong (doi:10.1136/bmj.h4597). Health professionals and lay people use them to monitor, manage, and even treat conditions. But apps are not heavily regulated. Compliance focuses on data protection and honest advertising, with few apps categorised as “medical devices” that need regulation by such organisations as the UK Medicines and Healthcare Products Regulatory Agency or the US Food and Drug Administration. The NHS Choices Health Apps Library lists apps found to be clinically safe and legally compliant. Meanwhile the Royal College of Physicians advises its members to use only apps that have a CE …
Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.
Authors: M Loeffler, V Diehl, M Pfreundschuh, U Rühl, D Hasenclever, H Nisters-Backes, M Sieber, H Tesch, J Franklin, W Geilen, H Bartels, C Cartoni, G Dölken, J Enzian, R Fuchs, W Gassmann, H Gerhartz, U Hagen-Aukamp, E Hiller, H Hinkelbein, W Hinterberger, H Kirchner, P Koch, B Krüger, E W Schwarze
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.
Results of an electronic survey of British Association of Dermatologists members: nicorandil ulceration
Authors: V.M. Smith, C.C. Lyon
Journal: British Journal of Dermatology (2013)

Journal Article Results of an electronic survey of British Association of Dermatologists members: nicorandil ulceration Get access V.M. Smith, V.M. Smith Department of Dermatology, Chapel Allerton Hospital, Leeds, U.K Search for other works by this author on: Oxford Academic Google Scholar C.C. Lyon C.C. Lyon Department of Dermatology, York Hospital, York, U.K. E‐mail: vanessasmith@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 5, 1 May 2013, Pages 1136–1137, https://doi.org/10.1111/bjd.12199 Published: 01 May 2013
A comparison of the Yan and a dosimeter method for methacholine challenge in experienced and inexperienced subjects
Authors: A J Knox, A Wisniewski, S Cooper, A E Tattersfield
Journal: European Respiratory Journal (1991)

Bronchial reactivity is being measured with increasing frequency in epidemiological studies, but there debate continues about the relative merits of the different methods used to measure reactivity, particularly for subjects with no previous experience of reactivity testing as is the case in epidemiological studies. Repeatability is likely to improve with practice, and laboratory based studies on experienced subjects may overestimate the repeatability of a test in inexperienced subjects. We have compared the repeatability of the Yan method with a dosimeter (Mefar) method of administering methacholine to 40 asthmatic subjects: 20 with experience of methacholine challenge on at least six previous occasions and 20 with no previous experience. Subjects attended the laboratory on four days within a two week period, at the same time of day. A methacholine challenge was performed on two occasions using the Yan method and on two occasions using the dosimeter. Methacholine responsiveness was measured as the provocative dose causing a 20% reduction in forced expiratory volume in one second (PD20FEV1). Geometric mean PD20FEV1 values with the Yan method were 1.14 doubling doses (DD) of methacholine higher than with the dosimeter method. In the experienced subjects, the 95% range for a single estimate was +/- 1.56 DD for the Yan method and +/- 1.37 DD for the dosimeter method. In the inexperienced subjects, the 95% ranges were +/- 2.65 and +/- 1.87 DD for the Yan and dosimeter methods, respectively. Thus, the differences in repeatability between the Yan and dosimeter methods, were small; experienced subjects gave more repeatable values than inexperienced subjects.
Arterial blood gas analysis after 120 minutes of noninvasive positive pressure ventilation can predict outcome in acute cardiogenic pulmonary oedema
Authors: Rodolfo Ferrari, Fabrizio Giostra, Francesca Nastasi, Roberto Lazzari, Luigi Bolondi, Mario Cavazza
Journal: European Respiratory Journal (2012)

Background   Noninvasive positive pressure ventilation (NIPPV) is first line intervention in Acute Cardiogenic Pulmonary Oedema (ACPO). Arterial Blood Gas Analysys (ABG) is largely available in clinical practice in the Emergency Department (ED)    Aims   To assess the role of ABG to predict outcome in patients with ACPO treated by NIPPV    Materials and Methods   Treatment failure defined as hospital mortality or need for invasive mechanical ventilation. Observational clinical study in the ED of a University teaching Hospital during 5 months, including every patient emergently admitted for ACPO and treated with first-line NIPPV, referring to an institutional protocol.    Results   214 patients included. Failure rate 14.5%.    Conclusions   In patients with ACPO treated with NIPPV, ABG at presentation is not able to carefully predict outcome. After 609 of NIPPV both groups (success versus failure) improved without any significant difference. The improvement of ABG after 1209 is associated with success; these patients will likely benefit from continuation of NIPPV. The inability to improve gas exchange after 1209 of NIPPV in ACPO is predictor of failure; these patients should be closely monitored with a low threshold for endotracheal intubation.
Somatotroph Hyperplasia
Authors: M. O. Thorner, R. L. Perryman, M. J. Cronin, A. D. Rogol, M. Draznin, A. Johanson, W. Vale, E. Horvath, K. Kovacs
Journal: Journal of Clinical Investigation (1982)

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95±9.4 ng/ml; mean±SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm3) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract.