tbuckley/cabot-search huggingface dataset:
Abstract 18271: The Association Between Obesity and Coronary Artery Disease Detected During Non-Emergent Angiography: a Comparison Between Black and White Patients
Authors: Caleb M Stalls, Matthew A Triplette, Anthony J Viera, Donald E Pathman, Mauricio G Cohen, Joseph S Rossi
Journal: Circulation (2011)

Introduction: Despite known associations between obesity and the development of cardiovascular disease, the relationship between obesity as reflected by BMI and angiographically demonstrated CAD is not fully understood. Moreover, this relationship has not been adequately defined in black patients, a group demonstrated to have lower rates of angiographic CAD despite higher rates of traditional CAD risk factors, cardiovascular events, and CAD-related mortality. Methods: Using an angiography database from a single academic hospital, we studied patients undergoing first-time, non-emergent angiography from 2001 to 2010. From this cohort, we selected those lacking a previous CAD diagnosis, without previous cardiac intervention, and with complete anthropomorphic measures and outcome data. Using models that controlled for patient demographics and CAD risk factors, we compared rates of angiographic disease for blacks and whites by obesity status (BMI ≥ 30 kg/m2). Significant CAD was defined by the presence of a significant lesion (≥50% stenosis in the left main artery or ≥70% stenosis elsewhere), and also quantified by a modified Gensini score of global disease. Results: We identified 4,022 white and 1,963 black eligible patients. Black patients had higher rates of diabetes and hypertension, and were more likely to be obese than whites (OR 1.85; 95% CI 1.65-2.06). Nevertheless, black patients were less likely to have a significant stenosis (adjusted OR 0.57; 95% CI 0.48-0.66), and were found to have a lower mean Gensini score (7.33 vs. 8.83, P=0.001). Obesity was not associated with the presence of CAD. In fact, black obese patients were significantly less likely to have a severe stenosis than their non-obese counterparts, and there was a non-significant trend for obese patients of both races to have less disease than non-obese patients using the Gensini score. Conclusions: Black patients in this cohort were more likely to be obese than white patients yet were far less likely to have significant CAD. Moreover, obesity itself was not positively associated with the presence or severity of CAD, suggesting that obesity may lead to cardiovascular morbidity and mortality by mechanisms other than the development of atherosclerosis, particularly in black patients.
hTERT Is Expressed in Cancer Cell Lines Despite Promoter DNA Methylation by Preservation of Unmethylated DNA and Active Chromatin around the Transcription Start Site
Authors: Rebekah L. Zinn, Kevin Pruitt, Sayaka Eguchi, Stephen B. Baylin, James G. Herman
Journal: Cancer Research (2007)

Abstract hTERT, which encodes the catalytic subunit of telomerase and is expressed in most immortalized and cancer cells, has been reported to have increased DNA methylation in its promoter region in many cancers. This pattern is inconsistent with observations that DNA methylation of promoter CpG islands is typically associated with gene silencing. Here, we provide a comprehensive analysis of promoter DNA methylation, chromatin patterns, and expression of hTERT in cancer and immortalized cells. Methylation-specific PCR and bisulfite sequencing of the hTERT promoter in breast, lung, and colon cancer cells show that all cancer cell lines retain alleles with little or no methylation around the transcription start site despite being densely methylated in a region 600 bp upstream of the transcription start site. By real-time reverse transcription-PCR, all cancer cell lines express hTERT. Chromatin immunoprecipitation (ChIP) analysis reveals that both active (acetyl-H3K9 and dimethyl-H3K4) and inactive (trimethyl-H3K9 and trimethyl-H3K27) chromatin marks are present across the hTERT promoter. However, using a novel approach combining methylation analysis of ChIP DNA, we show that active chromatin marks are associated with unmethylated DNA, whereas inactive marks of chromatin are associated with methylated DNA in the region around the transcription start site. These results show that DNA methylation patterns of the hTERT promoter (−150 to +150 around the transcription start) are consistent with the usual dynamics of gene expression in that the absence of methylation in this region and the association with active chromatin marks allow for the continued expression of hTERT. [Cancer Res 2007;67(1):194–201]
Common Questions About Neonatal Jaundice
Authors: Megan A. Moreno
Journal: JAMA Pediatrics (2015)

Yvonne W. Wu, MD, MPH; Michael W. Kuzniewicz, MD, MPH; Andrea C. Wickremasinghe, MD; Eileen M. Walsh, RN, MPH; Soora Wi, MPH; Charles E. McCulloch, PhD; Thomas B. Newman, MD, MPH
ER stress response plays an important role in aggregation of α-synuclein
Authors: Peizhou Jiang, Ming Gan, Abdul Shukkur Ebrahim, Wen-Lang Lin, Heather L Melrose, Shu-Hui C Yen
Journal: Molecular Neurodegeneration (2010)

Abstract Background Accumulation of filamentous α-synuclein as Lewy bodies is a hallmark of Parkinson's disease. To identify the mechanisms involved in α-synuclein assembly and determine whether the assemblies are cytotoxic, we developed a cell model (3D5) that inducibly expresses wild-type human α-synuclein and forms inclusions that reproduce many morphological and biochemical characteristics of Lewy bodies. In the present study, we evaluated the effects of several histone deacetylase inhibitors on α-synuclein aggregation in 3D5 cells and primary neuronal cultures. These drugs have been demonstrated to protect cells transiently overexpressing α-synuclein from its toxicity. Results Contrary to transient transfectants, the drug treatment did not benefit 3D5 cells and primary cultures. The treated were less viable and contained more α-synuclein oligomers, active caspases 3 and 9, as well as ER stress markers than non-treated counterparts. The drug-treated, induced-3D5 cells, or primary cultures from transgenic mice overexpressing (&lt;2 fold) α-synuclein, displayed more α-synuclein oligomers and ER stress markers than non-induced or non-transgenic counterparts. Similar effects were demonstrated in cultures treated with tunicamycin, an ER stressor. These effects were blocked by co-treatment with salubrinal, an ER stress inhibitor. In comparison, co-treatment with a pan caspase inhibitor protected cells from demise but did not reduce α-synuclein oligomer accumulation. Conclusions Our results indicate that an increase of wild-type α-synuclein can elicit ER stress response and sensitize cells to further insults. Most importantly, an increase of ER stress response can promote the aggregation of wild type α-synuclein.
Cyclo-oxygenase products released by low pH have capsaicin-like actions on sensory nerves in the isolated guinea pig heart
Authors: A. Franco-Cereceda, G. Kallner, J. M Lundberg
Journal: Cardiovascular Research (1994)

Journal Article Cyclo-oxygenase products released by low pH have capsaicin-like actions on sensory nerves in the isolated guinea pig heart Get access Anders Franco-Cereceda, Anders Franco-Cereceda Department of Thoracic Surgery, Karolinska Hospital, Box 60 500, S-104 01 Stockholm, Sweden: A Franco-Cereceda, G Källner; Department of Pharmacology, Karolinska Institute, Stockholm, Sweden: J M Lundberg. Correspondence to Dr Franco-Cereceda. Search for other works by this author on: Oxford Academic PubMed Google Scholar Göran Källner, Göran Källner Department of Thoracic Surgery, Karolinska Hospital, Box 60 500, S-104 01 Stockholm, Sweden: A Franco-Cereceda, G Källner; Department of Pharmacology, Karolinska Institute, Stockholm, Sweden: J M Lundberg. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jan M Lundberg Jan M Lundberg Department of Thoracic Surgery, Karolinska Hospital, Box 60 500, S-104 01 Stockholm, Sweden: A Franco-Cereceda, G Källner; Department of Pharmacology, Karolinska Institute, Stockholm, Sweden: J M Lundberg. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 3, March 1994, Pages 365–369, https://doi.org/10.1093/cvr/28.3.365 Published: 01 March 1994 Article history Received: 10 September 1993 Accepted: 27 October 1993 Published: 01 March 1994
FORMATION AND BIOLOGIC ROLE OF POLYOMA VIRUS-ANTIBODY COMPLEXES
Authors: Michael B. A. Oldstone, Neil R. Cooper, David L. Larson
Journal: The Journal of Experimental Medicine (1974)

Interaction of polyoma virus, specific antibody, and complement has been studied. Firm evidence has been gathered that C1 through C3 and not C5 through C9 enhance neutralization of virus-antiviral antibody (V-Ab) complexes. C enhancement of neutralization occurs primarily by agglutination of V-Ab complexes and not by virion lysis or attachment of large protein molecules to the V-Ab complex. In this model, binding of C1, 4, 2, 3 to the V-Ab complex may explain why some viruses concentrate in or infect certain cells bearing C3 receptors such as B lymphocytes, macrophages, and monocytes.
The effect of topical cyclosporin on the immediate shedding of human scalp hair grafted onto nude mice
Authors: A. GILHAR, T. PILLAR, A. ETZIONI
Journal: British Journal of Dermatology (1988)

Considerable evidence now exists that cyclosporin (CyA) has a stimulatory effect on hair growth. Previously, we demonstrated the systemic effect of CyA on hair growth using an experimental model of human scalp skin graft transplanted onto nude mice and rats. In the present study we used this model to investigate the effect of topical CyA on human hair growth. One group of 15 mice was treated with topical CyA in olive oil, and a second group of 10 mice with olive oil only. The numbers of grafts with hair and the number of hairs per graft in the different groups were compared. A statistically significant delay in hair shedding appeared from day 24 onwards in the CyA treated group. This pilot study supports the possibility that CyA may be effective in the treatment of alopecia.
T cell responses to a <i>Parietaria judaica</i> pollen extract: comparison between <i>Parietaria</i>‐sensitive patients, other atopics and healthy controls
Authors: G. Di Felice, A. Mari, N. Mucci, C. Afferni, G. Bruno, G. Pini
Journal: Allergy (1989)

We investigated the in vitro proliferation of peripheral blood mononuclear cells (PBMC) from Parietaria-allergic subjects, atopic patients with other sensitizations and healthy controls to Parietaria judaica pollen extracts. PBMC from almost all 44 subjects, divided into five groups (Parietaria-, grass-, Parietaria and grass-, Dermatophagoides-sensitive patients and normal individuals) were able to proliferate in response to the extract without statistically significant differences between groups. Mean values of the stimulation indexes for the five groups were respectively: 10.73, 3.18, 5.50, 10,56, 9.28. The results of separation experiments showed that the responding cells were T lymphocytes. Mitogenic effect of the Parietaria pollen extract was excluded by the absence of proliferative PBMC response from cord blood of seven newborns. These results indicate that Parietaria-sensitive, other atopics and normal individuals have Parietaria-specific T cells able to proliferate in vitro to Parietaria allergens.
Desk Reference of Clinical Pharmacology
Authors: Bruce A. Waldrop
Journal: JAMA (2008)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients
Authors: B A Walker, C P Wardell, A Brioli, E Boyle, M F Kaiser, D B Begum, N B Dahir, D C Johnson, F M Ross, F E Davies, G J Morgan
Journal: Blood Cancer Journal (2014)

Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including IGH, IGK and IGL, which juxtapose the immunoglobulin (Ig) enhancers next to MYC in 8/23 samples. The remaining samples had partner loci including XBP1, FAM46C, CCND1 and KRAS, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of MYC in these samples. Patients with MYC translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near MYC result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of MYC and an aggressive disease phenotype.
Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.
Authors: D B Buxton, F V Mody, J Krivokapich, M E Phelps, H R Schelbert
Journal: Circulation (1992)

BACKGROUND Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVO2 in postischemic myocardium is unknown. To address these issues, chronically instrumented dogs were studied serially over 1 month after transient left anterior descending coronary artery (LAD) occlusion, using positron emission tomography. METHODS AND RESULTS Dynamic imaging protocols were used in conjunction with tracer kinetic models to quantify blood flow and metabolic rates. Myocardial sectors were defined as normal, predominantly reversibly injured, and infarct-containing, based on occlusion blood flow images and postmortem histochemistry. Myocardial blood flow and metabolism were homogeneous at baseline. During LAD occlusion for 3 hours, myocardial blood flow in reversibly injured and infarct-containing sectors (determined with 13NH3) was decreased to 46% and 23%, respectively, of blood flow in normal tissue. MVO2, determined with [1-11C]acetate, was decreased less than myocardial blood flow, consistent with increased oxygen extraction in the ischemic tissue. After reperfusion, blood flow normalized rapidly in reversibly injured tissue but remained depressed in infarct-containing sectors. Regional myocardial function, assessed by two-dimensional echocardiography, was severely depressed during occlusion and did not improve significantly until 1 week after reperfusion. MVO2 remained depressed after reperfusion in both reversibly injured and infarct-containing sectors, did not improve from occlusion levels until 1 week after reperfusion, and remained significantly depressed 1 month after reperfusion even in reversibly injured sectors; [1-11C]palmitate kinetics were also abnormal in postischemic tissue. As reported previously, glucose metabolic rates were increased relative to baseline in normal but not in postischemic tissue 3 hours after reperfusion. Subsequently, glucose metabolism tended to be higher in postischemic relative to normal myocardium. CONCLUSIONS The results demonstrate decreased oxidative metabolism in postischemic tissue, with concomitant abnormalities in palmitate kinetics and glucose metabolism. Oxidative metabolism and regional function demonstrated a parallel recovery with time.
The end of a story
Authors: M. Mughal
Journal: BMJ (1995)

Nothing is here for tears, nothing to Wail or knock the breast; no weakness, No contempt, dispraise or blame; Nothing but well and fair.…

JOHN MILTON

Six years ago I wrote a personal view article about my wife, Indrani. She died two days ago and I can now complete her story. We were married for 19 years and have a 16 year old daughter. Indrani had suffered from rheumatoid arthritis from the age of 6. We had hoped that her diseasewould eventually burn out, but instead it became more aggressive. Over the years she had had both hips and knees replaced and spent a lot of time in hospital. In the last four years her erythrocyte sedimentation rate was consistently over 100 mm in the first hour and her haemoglobin rarely exceeded 90 g/l. She suffered frequent flare ups of widespread inflammation that would lay her low for days on end. But she kept bouncing back, remaining ambulant with crutches, and recently even took up studying Spanish and flower arranging. That was until 10 weeks ago.

She then started with crops of vasculitic rashes. One morning she woke complaining of breathlessness, a new symptom for her. Her legs were oedematous and I could hear crepitations on both sides of the chest. A chest radiograph confirmed cardiomegaly and pulmonary oedema. Although the heart failure improved with diuretics, the oedema got progressively worse. Further investigations showed raised urea and creatinine concentrations, low albumin, and heavy proteinuria. The spectre of amyloid was raised. Before this could be investigated any further, she suddenly developed pleuritic chest pain one night, and on examining her I noted a pleural rub and dullness at the …
Nontoxigenic protein A vaccine for methicillin-resistant <i>Staphylococcus aureus</i> infections in mice
Authors: Hwan Keun Kim, Alice G. Cheng, Hye-Young Kim, Dominique M. Missiakas, Olaf Schneewind
Journal: The Journal of Experimental Medicine (2010)

The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. aureus is not associated with protective immunity. This phenomenon involves staphylococcal protein A (SpA), an S. aureus surface molecule that binds to Fcγ of immunoglobulin (Ig) and to the Fab portion of VH3-type B cell receptors, thereby interfering with opsonophagocytic clearance of the pathogen and ablating adaptive immune responses. We show that mutation of each of the five Ig-binding domains of SpA with amino acid substitutions abolished the ability of the resulting variant SpAKKAA to bind Fcγ or Fab VH3 and promote B cell apoptosis. Immunization of mice with SpAKKAA raised antibodies that blocked the virulence of staphylococci, promoted opsonophagocytic clearance, and protected mice against challenge with highly virulent MRSA strains. Furthermore, SpAKKAA immunization enabled MRSA-challenged mice to mount antibody responses to many different staphylococcal antigens.
Demonstration of modified inactive first component of complement (C1) inhibitor in the plasmas of C1 inhibitor-deficient patients.
Authors: B L Zuraw, J G Curd
Journal: Journal of Clinical Investigation (1986)

The first component of complement (C1) inhibitor plays a critical role in the regulation of the classical complement pathway and the contact system, and the deficiency of C1 inhibitor protein or function is associated with recurrent angioedema. In this study we evaluated the size of the C1 inhibitor antigens present in the plasmas of C1 inhibitor-deficient patients. We found that the C1 inhibitor in the plasmas existed in three forms: high molecular weight forms in complex with proteases, native 110-kD C1 inhibitor, and a modified inactive 94-kD form. The proportion of the total C1 inhibitor in the 94-kD form was 28% in nine hereditary angioedema patients, 92% in five acquired C1 inhibitor-deficiency patients, and 1.2% in five normal controls. In vitro activation of normal plasma with kaolin, but not heat-aggregated gamma-globulin generated 94-kD C1 inhibitor from 110-kD C1 inhibitor. Neither kaolin activation nor heat-aggregated gamma-globulin activation generated 94-kD C1 inhibitor in Hageman factor-deficient plasma. These results suggest that 94-kD C1 inhibitor is generated in vitro by activation of the contact system. The in vivo mechanism of 94-kD C1 inhibitor generation in C1 inhibitor-deficient patients is not known.
Thrombopoietin promotes NHEJ DNA repair in hematopoietic stem cells through specific activation of Erk and NF-κB pathways and their target, IEX-1
Authors: Bérengère de Laval, Patrycja Pawlikowska, Daniela Barbieri, Corinne Besnard-Guerin, Alba Cico, Rajiv Kumar, Murielle Gaudry, Véronique Baud, Françoise Porteu
Journal: Blood (2013)
23 THE SCAVENGER RECEPTOR D6 MODULATES INFLAMMATION DURING LIVER INJURY BY DEGRADATION OF INFLAMMATORY CC CHEMOKINES
Authors: M.-L. Berres, M. Moreno Zaldivar, P. Schmitz, K. Pauels, S.A. Lira, C. Trautwein, F. Tacke, H.E. Wasmuth
Journal: Journal of Hepatology (2009)
Effect of Stored-Blood Transfusion on Oxygen Delivery in Patients With Sepsis
Authors: Paul E. Marik
Journal: JAMA (1993)

Red blood cell transfusion is commonly used to augment systemic oxygen delivery to supranormal levels in patients with sepsis. However, clinical studies have not consistently demonstrated that this therapeutic maneuver is accompanied by an increase in oxygen utilization at either the whole-body level or within individual organs.To determine the effect of red blood cell transfusion on gastrointestinal and whole-body oxygen uptake.Prospective, controlled, interventional study.Multidisciplinary intensive care unit of a tertiary care teaching hospital.Twenty-three critically ill patients with sepsis undergoing mechanical ventilation.Systemic oxygen uptake was measured by indirect calorimetry and calculated by the Fick method. Gastric intramucosal pH as measured by tonometry was used to assess changes in splanchnic oxygen availability. Measurements were made prior to transfusion of 3 U of packed red blood cells. These were then repeated immediately following transfusion, as well as 3 and 6 hours later. There was no increase in systemic oxygen uptake measured by indirect calorimetry in any of the patients studied for up to 6 hours posttransfusion (including those patients with an elevated arterial lactate concentration). However, the calculated systemic oxygen uptake increased in parallel with the oxygen delivery in all the patients. More importantly, we found an inverse association between the change in gastric intramucosal pH and the age of the transfused blood (r = -.71; P < .001). In those patients receiving blood that had been stored for more than 15 days, the gastric intramucosal pH consistently decreased following the red blood cell transfusion.We failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis. Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia. We postulate that the poorly deformable transfused red blood cells cause micro-circulatory occlusion in some organs, which may lead to tissue ischemia in some organs.