tbuckley/cabot-search huggingface dataset:
Association of body mass index with the development of methacholine airway hyperresponsiveness in men: the Normative Aging Study
Authors: A A Litonjua, D Sparrow, J C Celedon, D DeMolles, S T Weiss
Journal: Thorax (2002)

The rising prevalence of asthma in developed nations may be associated with the rising prevalence of obesity in these same nations. The relationship between body mass index (BMI) and the development of an objective marker for asthma, methacholine airway hyperresponsiveness (AHR), was investigated in adult men.Sixty one men who had no AHR at initial methacholine challenge testing but who developed AHR about 4 years later and 244 matched controls participated in the study. The effects of initial BMI and change in BMI on development of AHR were examined in conditional logistic regression models.Initial BMI was found to have a non-linear relationship with development of AHR. Compared with men with initial BMI in the middle quintile, men with BMI in the lowest quintile (BMI=19.8-24.3 kg/m(2)) and those with BMI in the highest quintile (BMI >29.4 kg/m(2)) were more likely to develop AHR: OR=7.0 (95% CI 1.8 to 27.7) and OR=10.0 (95% CI 2.6 to 37.9), respectively. These results remained significant after controlling for age, smoking, IgE level, and initial FEV(1). In addition, there was a positive linear relationship between change in BMI over the period of observation and the subsequent development of AHR.In this cohort of adult men, both a low BMI and a high BMI were associated with the development of AHR. For men with a low initial BMI the increased risk for development of AHR appears to be partly mediated by a gain in weight. The effect of BMI on AHR may suggest mechanisms in the observed associations between obesity and asthma.
The Bronchial Arteries in Pulmonary Emphysema
Authors: L. Cudkowicz, J. B. Armstrong
Journal: Thorax (1953)

The changes described varied from an obliterative arteritis to patches of atheroma.Loeschcke referred to the loss of pulmonary capillaries as the cause of the pallor of emphysematous lungs, and contended that Kapillarschwund preceded the development of the lung lesions.Gilmour and Evans suggested that a weakness of the media of the pulmonary arteries had predisposed to endarteritis obliterans.This they had observed in a case of primary pulmonary hypertension.Brenner, however, believed that increasing degrees of arteriosclerosis in the lungs of patients over 40 occurred irrespective of pulmonary disease.Whereas lesions affecting the pulmonary arteries in pulmonary emphysema have been studied, the pathology of the bronchial arteries in this disease is more obscure.In the course of investigations of the bronchial arteries in a variety of patho- logical lung conditions, it became evident to us that in cases coming to necropsy with a clinical diagnosis of pulmonary emphysema, and in others in which necropsy revealed bullous emphysema of the lungs, lesions in the bronchial arteries could be demonstrated.It is the purpose of this paper to describe these findings in the bronchial arteries, to correlate them, as far as possible, with other pathological and clinical features, and to assess their relevance in relation to this group of respiratory disorders.
HDMX regulates p53 activity and confers chemoresistance to 3-Bis(2-chloroethyl)-1-nitrosourea
Authors: Genglin Jin, Stephen Cook, Bo Cui, William C. Chen, Stephen T. Keir, Patrick Killela, Chunhui Di, Cathy A. Payne, Simon G. Gregory, Roger McLendon, Darell D. Bigner, Hai Yan
Journal: Neuro-Oncology (2010)

Glioblastoma multiforme (GBM) is one of the deadliest tumors afflicting humans, and the mechanisms of its onset and progression remain largely undefined. Our attempts to elucidate its molecular pathogenesis through DNA copy-number analysis by genome-wide digital karyotyping and single nucleotide polymorphism arrays identified a dramatic focal amplification on chromosome 1q32 in 4 of 57 GBM tumors. Quantitative real-time PCR measurements revealed that HDMX is the most commonly amplified and overexpressed gene in the 1q32 locus. Further genetic screening of 284 low- and high-grade gliomas revealed that HDMX amplifications occur solely in pediatric and adult GBMs and that they are mutually exclusive of TP53 mutations and MDM2 amplifications. Here, we demonstrate that HDMX regulates p53 to promote GBM growth and attenuates tumor response to chemotherapy. In GBM cells, HDMX overexpression inhibits p53-mediated transcriptional activation of p21, releases cells from G0 to G1 phase, and enhances cellular proliferation. HDMX overexpression does not affect the expression of PUMA and BAX proapoptotic genes. While in GBM cells treated with the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), HDMX appears to stabilize p53 and promote phosphorylation of the DNA double-stranded break repair protein H2AX, up-regulate the DNA repair gene VPX, stimulate DNA repair, and confer resistance to BCNU. In summary, HDMX exhibits bona fide oncogenic properties and offers a promising molecular target for GBM therapeutic intervention.
Heterogeneity of Responses to Real-Time Continuous Glucose Monitoring (RT-CGM) in Patients With Type 2 Diabetes and Its Implications for Application
Authors: Stephanie J. Fonda, Sara J. Salkind, M. Susan Walker, Mary Chellappa, Nicole Ehrhardt, Robert A. Vigersky
Journal: Diabetes Care (2012)

To characterize glucose response patterns of people who wore a real-time continuous glucose monitor (RT-CGM) as an intervention to improve glycemic control. Participants had type 2 diabetes, were not taking prandial insulin, and interpreted the RT-CGM data independently.Data were from the first 12 weeks of a 52-week, prospective, randomized trial comparing RT-CGM (n = 50) with self-monitoring of blood glucose (n = 50). RT-CGM was used in 8 of the first 12 weeks. A1C was collected at baseline and quarterly. This analysis included 45 participants who wore the RT-CGM ≥4 weeks. Analyses examined the RT-CGM data for common response patterns-a novel approach in this area of research. It then used multilevel models for longitudinal data, regression, and nonparametric methods to compare the patterns of A1C, mean glucose, glycemic variability, and views per day of the RT-CGM device.There were five patterns. For four patterns, mean glucose was lower than expected as of the first RT-CGM cycle of use given participants' baseline A1C. We named them favorable response but with high and variable glucose (n = 7); tight control (n = 14); worsening glycemia (n = 6); and incremental improvement (n = 11). The fifth was no response (n = 7). A1C, mean glucose, glycemic variability, and views per day differed across patterns at baseline and longitudinally.The patterns identified suggest that targeting people with higher starting A1Cs, using it short-term (e.g., 2 weeks), and monitoring for worsening glycemia that might be the result of burnout may be the best approach to using RT-CGM in people with type 2 diabetes not taking prandial insulin.
Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy
Authors: Mi Kyung Yu, Jinho Park, Sangyong Jon
Journal: Theranostics (2012)

Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications.
Even a Little Secondhand Smoke Is Dangerous
Authors: Stanton A. Glantz
Journal: JAMA (2001)

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
On the Kinetics of Polyplex Endocytic Trafficking: Implications for Gene Delivery Vector Design
Authors: M.Laird Forrest, Daniel W. Pack
Journal: Molecular Therapy (2002)

Synthetic gene therapy vectors must be designed to safely and efficiently escort DNA from outside the cell to the nucleus and to overcome several physical barriers that are obstacles to internalization, escape from endocytic vesicles, movement through the cytoplasm, and transport into the nucleus. By providing a firm foundation for polymer design, a quantitative understanding of polymer-mediated gene delivery mechanisms may allow more efficient and timely design of new vectors. We have used a flow-cytometry-based assay for investigating endocytic trafficking by quantitation of polyplex pH microenvironments. We investigated polyethylenimine (PEI)- and poly-L-lysine (PLL)-DNA trafficking, with and without the endosomotropic agent chloroquine. PLL-DNA complexes appear to be localized to early endocytic vesicles and are not trafficked to lysosomes. Further, chloroquine appears to facilitate PLL-mediated gene delivery by a mechanism other than buffering of endocytic compartments. Additionally, PEI does not appear to buffer endocytic compartments, but requires exposure to an acidic environment for efficient gene delivery.
Pinacidil-induced electrical heterogeneity and extrasystolic activity in canine ventricular tissues. Does activation of ATP-regulated potassium current promote phase 2 reentry?
Authors: J M Di Diego, C Antzelevitch
Journal: Circulation (1993)

BACKGROUND Pinacidil is known to augment a time-independent outward current in cardiac tissues by activating the ATP-regulated potassium channels. Activation of this current, IK-ATP, is thought to be responsible for increased potassium permeability in ischemia. The contribution of IK-ATP activation to arrhythmogenesis and the role of activation of this current in suppression of arrhythmias are areas of great interest and debate. Because electrical depression attending myocardial ischemia is more accentuated in ventricular epicardium than in endocardium, we endeavored to contrast the effects of pinacidil-induced IK-ATP activation on the electrophysiology of canine ventricular epicardium and endocardium. METHODS AND RESULTS Standard microelectrode techniques were used. Pinacidil (1 to 5 mumol/L) produced a marked dispersion of repolarization and refractoriness in isolated canine ventricular epicardium as well as between epicardium and endocardium. In endocardium, pinacidil abbreviated action potential duration (APD90) and refractoriness by 8.0 +/- 2.3%. In epicardium, the effects of pinacidil were nonhomogeneous. At some sites, pinacidil induced an all-or-none repolarization at the end of phase 1 of the action potential, resulting in 55.5 +/- 8.7% abbreviation of APD90 and refractoriness. Adjacent to these were sites at which the dome was maintained with only minor changes in APD and refractoriness. Extrasystolic activity displaying features of reentry was observed in isolated sheets of epicardium (63.2%) after exposure to pinacidil (1 to 5 mumol/L) but never in its absence. Dispersion of repolarization and ectopic activity was most readily induced in epicardium by a slowing of the stimulation rate in the presence of pinacidil. Electrical homogeneity was restored and arrhythmias abolished after washout of pinacidil or addition of either a transient outward current blocker, 4-aminopyridine, or a blocker of the ATP-regulated potassium channels, glybenclamide. CONCLUSIONS Our data suggest that the activation of IK-ATP can produce a marked dispersion of repolarization and refractoriness in epicardium as well as between epicardium and endocardium, leading to the development of extrasystolic activity via a mechanism that we have called phase 2 reentry. The available data also suggest that blockade of the transient outward current and/or the ATP-regulated potassium channels may be useful antiarrhythmic interventions under ischemic or "ATP depleted" conditions.
Effect of interleukin 2 on killer cell inhibitory receptors in patients with rheumatoid arthritis
Authors: T Kogure, A Niizawa, L X Hai, H Fujinaga, Y Shimada, H Ochiai, K Terasawa
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> The genes for killer cell inhibitory receptors (KIRs) have been cloned and their functions and responses to other molecules, including cytokines, have been partially clarified. However, the expression of KIRs has not been analysed in patients with autoimmune diseases, such as rheumatoid arthritis (RA), who are highly susceptible to microbial infection. Therefore, KIR expression on lymphocytes in patients with RA, and the regulation of KIR expression by interleukin 2 (IL2) in RA was investigated. <h3>METHODS</h3> CD158a/b expression on peripheral blood mononuclear cells (PBMC) obtained from 25 patients with RA and 14 healthy subjects was analysed by flow cytometry. Additionally, PBMC from the two groups of subjects were cultured in RPMI 1640 medium with or without IL2 for 48 hours, and then their CD158a/b expression was analysed. <h3>RESULTS</h3> The rate of CD158a expression on the CD8+ cells was lower in patients with RA than in healthy subjects, though there was no significant difference in the CD158a/b expression on the CD16+ cells between the two groups. The upregulation of CD16+CD158a/b+ cells in response to IL2 was significantly reduced in patients with RA compared with healthy subjects. <h3>CONCLUSION</h3> The reduced induction of KIR expression in response to IL2 may provide insight into the reason for the high susceptibility of patients with RA to microbial infection.
Principles of clinical gastroenterology
Authors: A J M Watson
Journal: Gut (2009)

Tadataka Yamada. Published by John Wiley Chichester 2008 662 hardcover, £85.00 978-1-4051-6910-3 

Principles of clinical gastroenterology is a companion to the Textbook of gastroenterology , both of which are edited by Tadataka Yamada. The latter was first published 20 years ago and, as Tadataka Yamada explains in his preface to the present book, aimed to be an encyclopaedic discussion of gastrointestinal and liver disorders. Textbook of gastroenterology contains sections on the symptoms and signs and the approach a clinician should take in clinical management. These parts of that book proved to be very popular and so Professor Yamada and his colleagues expanded and developed these sections into a second book, Principles of …
Update in Acute Lung Injury and Critical Care 2010
Authors: István Vadász, Jacob I. Sznajder
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

In this Update, we provide an overview of selected studies published in 2010 in the American Journal of Respiratory and Critical Care Medicine and other journals focusing on novel findings on acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS).We attempt to highlight key articles that advanced our understanding on clinical and basic aspects of critical illness.
The Quality of Health Care Delivered to Adults in the United States
Authors: Elizabeth A. McGlynn, Steven M. Asch, John Adams, Joan Keesey, Jennifer Hicks, Alison DeCristofaro, Eve A. Kerr
Journal: New England Journal of Medicine (2003)

We have little systematic information about the extent to which standard processes involved in health care--a key element of quality--are delivered in the United States.We telephoned a random sample of adults living in 12 metropolitan areas in the United States and asked them about selected health care experiences. We also received written consent to copy their medical records for the most recent two-year period and used this information to evaluate performance on 439 indicators of quality of care for 30 acute and chronic conditions as well as preventive care. We then constructed aggregate scores.Participants received 54.9 percent (95 percent confidence interval, 54.3 to 55.5) of recommended care. We found little difference among the proportion of recommended preventive care provided (54.9 percent), the proportion of recommended acute care provided (53.5 percent), and the proportion of recommended care provided for chronic conditions (56.1 percent). Among different medical functions, adherence to the processes involved in care ranged from 52.2 percent for screening to 58.5 percent for follow-up care. Quality varied substantially according to the particular medical condition, ranging from 78.7 percent of recommended care (95 percent confidence interval, 73.3 to 84.2) for senile cataract to 10.5 percent of recommended care (95 percent confidence interval, 6.8 to 14.6) for alcohol dependence.The deficits we have identified in adherence to recommended processes for basic care pose serious threats to the health of the American public. Strategies to reduce these deficits in care are warranted.
Protein kinase C isoform expression and regulation in the developing rat heart.
Authors: V O Rybin, S F Steinberg
Journal: Circulation Research (1994)

To determine whether age-dependent differences in cardiac responses to autonomic agonists could result from developmental changes in protein kinase C (PKC) isoform expression, we probed extracts from the fetal, neonatal, and adult heart as well as cultured neonatal and isolated adult ventricular myocytes with specific antisera to calcium-dependent (alpha and beta) and calcium-independent (delta, epsilon and zeta) isoforms of the enzyme. Although PKC-beta immunoreactivity could not be detected in cultured neonatal or isolated adult ventricular myocytes, adult and neonatal myocytes expressed multiple other isoforms of PKC. Our studies revealed an age-dependent decline in the immunoreactivity for three PKC isoforms. PKC-alpha was detected in extracts from the fetal and 2-day-old neonatal heart as well as cultured neonatal rat ventricular myocytes. Only faint PKC-alpha immunoreactivity was detected in extracts from the adult heart, and PKC-alpha was not detected in extracts from isolated adult ventricular myocytes, suggesting that PKC-alpha resides in nonmyocyte elements in the adult heart. PKC-delta also was detected in greater abundance in fetal and neonatal than in adult myocardial extracts. The decline in PKC-alpha and PKC-delta expression occurred during the first 2 postnatal weeks. PKC-zeta was detected in greatest abundance in extracts from the fetal heart. PKC-zeta expression declined markedly by the second postnatal day, and only faint PKC-zeta immunoreactivity was detected in extracts from adult myocardium. Failure to detect PKC-zeta in extracts from isolated adult ventricular myocytes suggests that PKC-zeta resides primarily in nonmyocyte elements in the adult heart. PKC-epsilon was detected in all preparations, but it was detected in greatest abundance in extracts from neonatal hearts. In vitro sympathetic innervation of previously noninnervated neonatal ventricular myocytes or in vivo chemical sympathectomy of the neonatal heart did not modulate PKC isoform expression, suggesting that sympathetic innervation does not significantly regulate PKC isoform expression. PKC-alpha partitioned to the soluble fraction of unstimulated myocytes and was selectively translocated to the particulate fraction by Ca2+. In contrast, a major portion of the novel PKC isoforms partitioned to the particulate fraction of unstimulated myocytes. The subcellular distribution of novel PKC isoforms was not influenced by Ca2+. 12-O-Tetradecanoylphorbol 13-acetate (TPA, 300 nmol/L) induced translocation of soluble PKC-alpha, PKC-delta, and PKC-epsilon to the particulate fraction at 30 minutes and complete (PKC-alpha and PKC-delta) or 80% (PKC-epsilon) downregulation at 24 hours. PKC-zeta was not affected by TPA.(ABSTRACT TRUNCATED AT 400 WORDS)
Low Insulin Sensitivity (<i>S</i>i = 0) in Diabetic and Nondiabetic Subjects in the Insulin Resistance Atherosclerosis Study
Authors: Steven M. Haffner, Ralph D’Agostino, Andreas Festa, Richard N. Bergman, Leena Mykkänen, Andrew Karter, Mohammed F. Saad, Lynne E. Wagenknecht
Journal: Diabetes Care (2003)

OBJECTIVE—To determine the meaning of Si = 0 derived from the frequently sampled intravenous glucose tolerance test. RESEARCH DESIGN AND METHODS—The issue of assessing insulin resistance in large studies is important because the most definitive method (“gold standard”), the hyperinsulinemic-euglycemic clamp, is expensive and invasive. The frequently sampled intravenous glucose tolerance test (FSIGTT) has been widely used, but in insulin-resistant subjects (especially diabetic subjects), it yields considerable numbers of subjects whose Si is zero. The interpretation of an Si equaling zero is unknown. RESULTS—To address this issue, we examined 1,482 subjects from the Insulin Resistance Atherosclerosis Study (IRAS) using an insulin-modified FSIGTT and minimal model calculation of Si. The proportion of insulin-resistant subjects (Si &amp;lt; 1.61 × 10−4 [min−1 · μU−1 · ml−1] based on the median of the nondiabetic population) was 38.6% in subjects with normal glucose tolerance (NGT), 74% in subjects with impaired glucose tolerance (IGT), and 92% in subjects with type 2 diabetes. The proportion of subjects with Si = 0 was 2.2% in subjects with NGT, 13.2% in subjects with IGT, and 35.7% in subjects with type 2 diabetes. In subjects with IGT, those with Si = 0 had significantly lower HDL cholesterol levels and higher BMI, waist circumference, fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), C-reactive protein (CRP), and 2-h insulin levels than insulin-resistant subjects with Si &amp;gt; 0. In type 2 diabetes, subjects with Si = 0 had significantly greater BMI and waist circumference and higher triglyceride, PAI-1, CRP, fibrinogen, and fasting and 2-h insulin levels than insulin-resistant subjects with Si &amp;gt; 0. In addition, diabetic subjects with Si = 0 had more metabolic disorders related to the insulin resistance syndrome than diabetic insulin-resistant subjects with Si &amp;gt; 0. CONCLUSIONS—We found very few subjects with Si = 0 among subjects with NGT and few subjects with Si = 0 among subjects with IGT. In contrast, Si = 0 was common in subjects with diabetes. Subjects with Si = 0 tended to have more features of the insulin resistance syndrome than other insulin-resistant subjects with Si &amp;gt; 0, as would be expected of subjects with almost no insulin-mediated glucose disposal, thus suggesting that subjects with Si = 0 are correctly classified as being very insulin resistant rather than having failed the minimal model program.