tbuckley/cabot-search huggingface dataset:
Adenoviruses Transport across a Polarized Monolayer of Caco-2 Cells by Transferrin Receptor-Mediated Transcytosis
Authors: Zeng B. Zhu, Sharmila K. Makhija, Baogen Lu, Minghui Wang, Meredith A. Preuss, Angel A. Rivera, Fen Zhou, Gene P. Siegal, Ronald D. Alvarez, David T. Curiel
Journal: Molecular Therapy (2004)

Adenoviral (Ad) vectors are commonly used in gene delivery because they have the capacity to infect a broad range of different cell types. Recent studies have identified a 46-kDa host cell membrane protein, coxsackie-adenovirus receptor (CAR), which serves as the primary receptor for Ad serotypes 2 and 5 as well as coxsackie B virus attachment to cells. Following binding to CAR, Ad interacts with a second receptor, av integrin, which facilitates virus internalization into cells. However, significant challenges exist to the efficient use of Ad vectors for in vivo gene delivery. For example, delivery to the airway luminal surface, urothelial cells and brain remain a challenge due to the epithelial and endothelial barriers. These cells, which are joined together by complex tight intercellular junctions, form a continuous wall against the passive paracellular movement of substances. For many disorders, this is an obstacle for effective transgene delivery.
Procaterol and Terbutaline in Bronchial Asthma
Authors: R. Dahl, H. Harving, J. Henriksen, K. Rønne, P. Schøler
Journal: Allergy (1985)

Procaterol, a new beta‐2 adrenoceptor stimulant, was studied in a double‐blind, placebo‐controlled, cross‐over trial in patients with bronchial asthma. Oral procaterol 50μg b.d., procaterol 100 μg b.d., and terbutaline 5 mg t.i.d., were compared when given randomly in 1‐week treatment periods. The best clinical effect was found with terbutaline. Both anti‐asthmatic and tremorgenic effects of procaterol were dose‐related. Procaterol appeared effective in the doses tested, and a twice daily regimen would appear to be suitable with this drug.
Abstract 3610: Comparative Effects of 3 Popular Diets on Lipids, Endothelial Function and Biomarkers of Atherothrombosis in the Absence of Weight Loss
Authors: Michael Miller, Valerie Beach, Charles Mangano, Jeffrey Rhyne, Christina Dobmeier, Danica Novacic, Robert A Vogel
Journal: Circulation (2007)

Background : While the effect of popular diets on weight loss has been extensively studied, less is known in the absence of weight loss. We hypothesized that a diet high in total and saturated fat would be associated with adverse effects on LDL-C, endothelial function and biomarkers of atherothrombosis compared to lower fat diets. Methods : We tested 3 popular diets, including Atkins (50% fat), South Beach (30% fat) and Ornish (10% fat) in a randomized and counterbalanced, crossover study. Subjects completed each of the three 4-week dietary intervention phases followed by a 4-week washout period. They were weighed weekly and caloric adjustments made if weight change exceeded 1 kg. At the completion of each dietary phase, 3-day food records were analyzed, fasting blood was sampled and brachial artery reactivity testing (BART) performed. Results : Eighteen of 26 adults (mean age: 30.6 ± 9.6 yrs, 50% female) completed all 3 dietary phases. There were no changes in weight at the conclusion of each phase. However, non-significant increases in LDL-C occurred during the Atkins phase (pre: 96.5, post: 112.9 mg/dL; P=0.12 ), whereas LDL-C was reduced during the Ornish (pre: 110.1, post: 84.6 mg/dL; P=0.006 ) and South Beach phases (pre: 101.7, post: 91.5 mg/dL; P=0.01 ). BART testing revealed a significant inverse correlation between flow-mediated vasodilation and intake of total fat (r 2 =−0.29; P=0.03 ), saturated fat (r 2 =−0.31; P=0.02 ) and monounsaturated fat (r 2 =−0.35; P=0.01 ). Microarray analysis demonstrated increased expression of several leukocyte biomarkers including, ICAM2 (37%; P=0.002 ), SELL (26%; P=0.007 ) and SOD1 (42%; P=0.04 ) at the completion of the Atkins diet compared to baseline. In contrast, expression of atherothrombotic biomarkers was not increased after the South Beach or Ornish phase. Conclusions: In the absence of weight loss, the high fat Atkins diet is associated with increased LDL-C, reduced endothelial vasoreactivity and increased expression of biomarkers of atherothrombosis. As such, these data suggest that isocaloric conversion to the Atkins diet may negatively impact cardiovascular health as compared to the South Beach or Ornish Diet.
Synbiotics prevent asthma-like symptoms in infants with atopic dermatitis
Authors: L. B. van der Aa, W. M. C. van Aalderen, H. S. A. Heymans, J. Henk Sillevis Smitt, A. J. Nauta, L. M. J. Knippels, K. Ben Amor, A. B. Sprikkelman
Journal: Allergy (2010)

Infants with atopic dermatitis (AD) have a high risk of developing asthma. We investigated the effect of early intervention with synbiotics, a combination of probiotics and prebiotics, on the prevalence of asthma-like symptoms in infants with AD. In a double-blind, placebo-controlled multicentre trial, ninety infants with AD, age <7\ months, were randomized to receive an extensively hydrolyzed formula with Bifidobacterium breve M-16V and a galacto/fructooligosaccharide mixture (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. After 1 year, the prevalence of respiratory symptoms and asthma medication use was evaluated, using a validated questionnaire. Also, total serum IgE and specific IgE against aeroallergens were determined. Seventy-five children (70.7% male, mean age 17.3 months) completed the 1-year follow-up evaluation. The prevalence of 'frequent wheezing' and 'wheezing and/or noisy breathing apart from colds' was significantly lower in the synbiotic than in the placebo group (13.9%vs 34.2%, absolute risk reduction (ARR) -20.3%, 95% CI -39.2% to -1.5%, and 2.8%vs 30.8%, ARR -28.0%, 95% CI -43.3% to -12.5%, respectively). Significantly less children in the synbiotic than in the placebo group had started to use asthma medication after baseline (5.6%vs 25.6%, ARR -20.1%, 95% CI -35.7% to -4.5%). Total IgE levels did not differ between the two groups. No children in the synbiotic and five children (15.2%) in the placebo group developed elevated IgE levels against cat (ARR -15.2%, 95% CI -27.4% to -2.9%). These results suggest that this synbiotic mixture prevents asthma-like symptoms in infants with AD.
Abstract 13320: Effect of Cardiovascular Comorbidities on the Mortality Risk Associated with Serum Potassium
Authors: Bertram Pitt, Allan J Collins, Nancy Reaven, Susan Funk, George L Bakris, David A Bushinsky
Journal: Circulation (2014)

Introduction: Both hypokalemia and hyperkalemia are known to be associated with an increased mortality risk. The serum potassium (K + ) levels associated with these risks and the relationships to comorbidity, however, are not well defined. We therefore evaluated the odds of death in patients with and without comorbid conditions, stratified by K + level. Methods: De-identified medical records (2007-2012) from a large U.S. population of persons ≥ 5 years of age with at least 2 K + readings were evaluated. Patients 45-64 years of age with comorbidities defined as CKD stages 3-5, heart failure, diabetes, hypertension, and cardiovascular disease (n=231,070) were identified from demographic data, ICD-9 codes and biochemical data, excluding those with acute kidney injury or end stage renal disease, and compared with controls having none of these conditions (n=146,645). A separate analysis of patients ≥ 65 years of age was performed. Index K + value was defined as the last reported value prior to pre-determined cut-off date. Mortality was evaluated through hospital discharge records and Social Security registry information. Results: Among patients aged 45-64 with comorbid conditions, index K + levels below 4.1 mEq/L and above 4.6 mEq/L demonstrate a significant increase in mortality (Figure). This finding was similar in patients ≥ 65 years of age. The general pattern remained after adjustments for demographic characteristics (sex, race) and subgroup analyses controlling for comorbidities associated with the propensity to develop hypo- and hyperkalemia. Conclusions: These results indicate that the level of potassium and the risk of mortality in patients with hypokalemia or hyperkalemia is highly associated with underlying disease; is significantly greater in patients with comorbid conditions; and is independent of demographic characteristics. The increased mortality in patients with comorbidity occurs even at K + levels within the usual normal laboratory range.
Gene Mutation Profiling of Breast Cancers for Clinical Decision Making
Authors: Vered Stearns, Ben Ho Park
Journal: JAMA Oncology (2015)

Drivers and Passengers in the Cart Before the HorseRecent advances in molecular profiling allow for a rapid and relatively inexpensive assessment of multiple altered genes or gene products from small amounts of tumor tissues or blood.The challenge ahead is how to properly incorporate these results into clinical practice, and how to provide patients with the best possible yet evidence-based care.Herein, we provide a brief overview of genetic mutation profiling with a focus on next-generation sequencing (NGS) and possible clinical utility. Mutation Detection TechniquesHighly sensitive techniques are now available to detect mutations quantitatively and qualitatively.Typically, NGS involves creating "libraries" of short DNA fragments that are then sequenced massively in parallel to identify genetic alterations in a tumor.Since there are only a few known "driver" genes (ie, genes implicated in carcinogenesis and/or drug resistance), most tests do not query the entire genome but instead incorporate select gene panels, generally consisting of 50 to 400 cancer-related genes.An assay may include all coding exons or only known "hotspot" regions within a given set of genes.
Fortnightly Review: Intermittent catheterisation: simple, safe, and effective but underused
Authors: G. M Hunt, P. Oakeshott, R. H Whitaker
Journal: BMJ (1996)

Twenty five years ago Lapides and coworkers showed that intermittent catheterisation was a safe and effective way of managing patients with urinary retention or incontinence due to neuropathic or hypotonic bladder.1 2 This technique has transformed the lives of people rendered housebound by bladder problems and has preserved the kidneys of children with spina bifida3 4 5 6 7 8 9 10 and of adults with spinal cord injury.11 12 13 14 15 Intermittent catheterisation is a clean but not sterile technique. It entails inserting a catheter into the bladder, emptying out all the urine, and then removing the catheter. This is performed several times a day by the patient or carer. It puts the patient in control of emptying the bladder and safeguards the kidneys by providing drainage.

#### Summary points

Incomplete emptying of bladder—A bladder that retains a large volume of residual urine soon fills to capacity, causing frequency, urgency, nocturia, or incontinence. Urinary stasis leads to urinary tract infections and calculi. By eliminating residual urine, intermittent catheterisation enables the bladder to function more effectively as a reservoir, relieves symptoms, and reduces the incidence of symptomatic urinary infections.3 9 16 22 25 28

Obstructive uropathy—Many patients with a neuropathic bladder have an overactive sphincter, causing obstruction of the bladder outlet and dilatation of the upper urinary tracts. A combination of a contracting urethral sphincter with hyperreflexic bladder contractions (detrusor-sphincter dyssynergia) accelerates the damage. If the obstruction of the bladder outlet is overcome by intermittent catheterisation then dilatation of the upper urinary tracts is reduced and renal function improved.6 22

Reflux nephropathy—Vesicoureteric reflux associated with neuropathic bladder often causes renal damage. The risk is increased by obstruction of the bladder outlet, high intravesical pressure, or urinary infection. Intermittent catheterisation can reduce or eliminate …
Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age
Authors: H. J. Deeg, H. M. Shulman, J. E. Anderson, E. M. Bryant, T. A. Gooley, J. T. Slattery, C. Anasetti, A. Fefer, R. Storb, F. R. Appelbaum
Journal: Blood (2000)
Fortnightly Review: Benign positional vertigo: recognition and treatment
Authors: T. Lempert, M. A Gresty, A. M Bronstein
Journal: BMJ (1995)

Dizziness is one of the most common complaints in general practice, and yet doctors often find it difficult to establish a firm diagnosis in individual patients.Benign positional vertigo accounts for about a fifth of the referrals to specialised vertigo clinics' and is the most commonly missed treatable condition.Fortu- nately, it can be readily diagnosed by positional testing.Recent insights into its pathophysiology have provided new means of effective treatment that can be applied in clinics.vertigo; viral neuronitis and head trauma are the most common, followed by vascular, inflammatory, and surgical damage to the labyrinth.In about 60% ofcases no apparent cause can be identified.4The condition tends to resolve spontaneously after several weeks or months.Some patients, however, experience recurrences months or years later.Variants range from a single shortlived episode to decades of suffering with only short remissions.
Dengue fever in returning travellers
Authors: Barbara J Bain, Matthew J Stubbs
Journal: American Journal of Hematology (2015)

Physicians and hematology laboratories in non-endemic regions need to be alert to the occurrence of tropical diseases in returning travellers.One such imported disease is dengue fever.The first patient was a 63-year-old febrile man on whom a blood count was requested by a general practitioner.The blood count showed: WBC 4.0 3 10 9 /l, Hb 143 g/l, platelet count 22 3 10 9 /l, neutrophil count 2.2 3 10 9 /l and lymphocyte count 1.0 3 10 9 /l.The blood film showed atypical lymphocytes (top two panels); some of these were plasmacytoid, some resembled immunoblasts and some had a hand-mirror shape.The laboratory staff noticed that the patient's name suggested a Sri Lankan origin and suspected dengue fever.The patient was found to have recently returned from Sri Lanka and the diagnosis was confirmed.The second patient was a 23-year-old man of Indian ethnic origin who became febrile two days after returning from India, where he had been back-packing.His blood count showed: WBC 3.2 3 10 9 /l, Hb 164 g/l, platelet count 22 3 10 9 /l, neutrophil count 0.9 3 10 9 /l and lymphocyte count 1.9 3 10 9 /l.His blood film showed moderate numbers of atypical lymphocytes (bottom two panels); most of these were nucleolated, some were plasmacytoid and hand-mirror forms were frequent.Both laboratory and clinical staff suspected dengue fever and this diagnosis was confirmed.In a patient who has visited an endemic area, the combination of severe thrombocytopenia and atypical lymphocytes without lymphocytosis raises the suspicion of dengue fever.The diagnostic value of atypical lymphocytes has been commented on previously [1].The total white cell count tends to be low normal or reduced and there may also be neutropenia.Patients with more severe disease can have evidence of a consumption coagulopathy.A hemophagocytic syndrome can occur [2] and exceptionally a plasmacytic leukemoid reaction has reported [3].Our two cases highlight the importance of assessing both clinical features and blood film morphology.
Abstract 859: Hypoxia-activated CXCR4 Expression In Cardiac Progenitor Cells For Replenishing Stem Cell Pool In Acute Ischemic Myocardium
Authors: Yao Liang Tang, Leping Shen, Keping Qian, M. Ian Phillips
Journal: Circulation (2007)

The resident cardiac progenitor cells (CPCs) have been identified in the adult myocardium, however, the CPC pool is rapidly depleted after acute myocardial infarction (AMI). The strategy to home ex vivo cultured CPCs to ischemic myocardium might be an important strategy to replenish resident CPC pool, and improve cardiac function. The CXC chemokine SDF-1α and its receptor CXCR4 have been identified as critical mediator for the ischemia-specific recruitment of progenitor cells, yet the level of CXCR4 expression in CPCs is quite low in normal conditions. Our previous studies showed that hypoxia can optimize CPCs via inducing functional CXCR4 expression in vitro, therefore, in this study, we want to investigate whether the transplantation of hypoxia treated CPCs (Hypo:CPCs) have the benefit of improving cardiac function resulted from increased cell homing in ischemic myocardium through mechanisms of hypoxia induced CXCR4 expression. To compare the homing capability between CPCs and Hypo:CPCs in response to endogenous SDF-1 signal in acute ischemic myocardium, we used retrovirus (pCL-MFG-β-gal) to label c-kit + Lin − CPCs with β-gal, and then injected labeled CPCs and Hypo:CPCs (1×10 6 ) intravenously via intra-jugular vein to mice 10 min after induction of MI in the C56BL/6 mice. We harvested the hearts 1d after cell transplantation to quantify the cell retention by chemiluminescent β-galactosidase assay. We observed that hypoxia treatment resulted in about 2.5 fold increase in β-gal cell recruitment in ischemic hearts (p&lt;0.001, n=7– 8/group), however, AMD3100 can partially reduce Hypo:CPCs homing, therefore, the beneficial effects of Hypo:CPCs transplantation were mediated primarily through increasing cell homing via SDF-1:CXCR4 binding within the ischemic hearts. In addtion, the infusion of Hypo:CPCs also led to improved left ventricular performance, as assessed by LV development pressure by Millar catheter, by 23.67% compared with CPCs at 1 month after cell therapy (p&lt;0.001, n=6/group). These results indicate that replenish CPC pool after AMI using ex vivo cultured CPC transplantation has significant beneficial effects on injured heart function dependent of hypoxia induced CXCR4 upregulation.
Abstract 11652: A Prospective Observational Review of Patients Undergoing the Novel ‘TS’ Approach to the Hybrid Atrial Fibrillation Procedure
Authors: Joseph J Tiano, Albert DiMeo, Lindsey Scierka, Rafael Squitieri
Journal: Circulation (2014)

Introduction: Historically, persistent atrial fibrillation (PeAF) and long standing persistent atrial fibrillation (LSPeAF) have been difficult to ablate with poor success rates despite multiple procedures. The advent of Hybrid AF procedures has improved success. However, endovascular mapping/ablation can be limited by edema when following an epicardial ablation. Therefore, we propose an alternative technique that emphasizes an endovascular first approach, transcatheter (T) preceding surgical (S). Hypothesis: Hybrid AF success rates can be increased for both PeAF and LSPeAF by the ‘TS’ Hybrid AF procedure defined by a comprehensive endovascular approach preceding and guiding the epicardial ablation which includes an extensive posterior wall ablation. Methods: We prospectively enrolled 31 patients over 24 months in a single center with the procedure performed over 24 hrs. Patients had a mean AF duration of 7 ± 4 years with 32% (n=10) having undergone prior ablations. Mean age was 64 ± 8 years with mean LA ...
Abstract 424: Vascular Smooth Muscle Cell Expression of S100a12 in Vivo Induces Enhanced Oxidative Stress &amp; Vascular Remodeling
Authors: Marion Hofmann Bowman, Jeannine Wilk, Gene Kim, Yanmin Zhang, Jalees Rehman, Elizabeth McNally
Journal: Circulation (2008)

S100A12 is a small calcium binding protein that is a signal transduction ligand of the receptor for advance glycation endproducts (RAGE). S100A12, like RAGE, is expressed in the vessel wall of atherosclerotic vasculature, particularly in smooth muscle cells (SMC). While RAGE has been extensively implicated in inflammatory states such as atherosclerosis, the role of S100A12 is less clear. We tested the hypothesis that expression of human S100A12 directly exacerbates vascular inflammation. Several lines of Bl6/J transgenic mice (tg) expressing human S100A12 in SMC under control of the SM22a promoter were generated. Primary aortic SMC from tg and wild type (wt) littermates were isolated and analyzed for (i) proliferation using MTS/Formazan Assay and BrdU incorporation, (ii) oxidative stress using using flow cytometry with MitoSOX antibody, oxidative DNA damage using immunofluorescence microscopy with anti-8-oxo-dG antibody, and NF-kB activation measured by EMSA and (iii) cytokine expression measured by IL-6 ELISA. Furthermore, the aortas from tg and wt mice were examined. Results: Tg but not wt SMC expressed S100A12 protein. Tg SMC had a significant 1.9 to 2.7 fold increase in conversion of MTS into Formazan at 24–96 hours likely reflective of increased metabolic activity since BrdU incorporation into DNA was less in tg compared to wt SMC (4% vs 21% positive BrdU nuclei, p &lt;0.05). Tg SMC showed significantly higher levels of mitochondrial generated ROS, nuclear staining for oxidative DNA damage which was not detected in the nuclei of wt SMC’s, and a 2.5 fold increase in NFkB activity. IL-6 production at baseline was higher in tg SMC’s (615 vs 213 pg/ml, p&lt; 0.05) and increased dramatically after LPS treatment (10 ng/ml) in tg SMC’s (2130 vs 415 pg/ml). Histologic examination of the thoracic aorta at 10 weeks of age revealed increased collagen deposition in the aortic media with fragmentation and disarray of elastic fibers. In vivo ultrasound revealed a progressive dilation of the aortic arch from age 10 weeks to 16 weeks of age (1.27 to 1.60 mm, p&lt;0.05) in tg but not in wt littermate mice (1.30 to 1.33 mm, p=0.1). These data reveal the novel finding that targeted expression of human S100A12 in SMC modulates oxidative stress, inflammation and vascular remodeling.