tbuckley/cabot-search huggingface dataset:
Deposits of terminal complement complex (TCC) in muscularis mucosae and submucosal vessels in ulcerative colitis and Crohn's disease of the colon.
Authors: T S Halstensen, T E Mollnes, O Fausa, P Brandtzaeg
Journal: Gut (1989)

Extensively washed, ethanol fixed and paraffin embedded colonic specimens from 15 patients with ulcerative colitis (UC) and nine patients with Crohn's disease (CD) of the colon, ileal specimens from six patients with CD of the ileum, and histologically normal control specimens obtained from 10 patients operated for colonic carcinoma, were examined by immunohistochemistry with a monoclonal antibody specific for a neoepitope in the C9 part of the terminal complement complex (TCC). The submucosal blood vessels in inflammatory bowel disease (IBD) showed significantly more TCC positivity than the controls, and vascular TCC deposition was statistically related (p less than 0.001) to degree of inflammation. Five of the six ileal CD specimens contained likewise vascular TCC deposits. In addition, five UC specimens and one colonic CD specimen contained TCC-positive fibrils in the muscularis mucosae or submucosa. There was no significant difference in vascular TCC deposits between UC and CD. The results suggested that terminal complement activation takes place in the intestinal lesions of IBD.
Effects of Cardiac Denervation on Development of Heart Failure and Catecholamine Desensitization
Authors: Naoki Sato, Stephen F. Vatner, You-Tang Shen, Raymond K. Kudej, Bijan Ghaleh-Marzban, Masami Uechi, Kuniya Asai, Israel Mirsky, Thomas A. Patrick, Richard P. Shannon, Dorothy E. Vatner
Journal: Circulation (1997)

Background Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. Methods and Results We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depletion of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf c ), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf c in heart failure were less ( P &lt;.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD ( P &lt;.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592±79 pg/mL) compared with intact dogs (576±81 pg/mL) in heart failure. Conclusions Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.
Intracellular pH of canine subendocardial Purkinje cells surviving in 1-day-old myocardial infarcts.
Authors: K P Dresdner, R P Kline, A L Wit
Journal: Circulation Research (1989)

A large reduction of intracellular potassium activity in depolarized subendocardial Purkinje fibers 24 hours after coronary artery ligation is accompanied by a much smaller increase in intracellular sodium activity. Similar intracellular ionic changes also occur during acute ischemia in ventricular muscle and are consistent with mechanisms based on intracellular acidification, which is known to occur in acutely ischemic muscle. To determine if canine subendocardial Purkinje cells 24 hours after myocardial infarction are also acidic, their intracellular pH, surface pH, and maximum diastolic potential (MDP) were measured with double-barrel pH-sensitive microelectrodes and compared with control fibers in noninfarcted hearts. In 12 mM bicarbonate Tyrode's solution (5% CO2-95% O2), the average intracellular pH was not significantly different (p greater than 0.25) for normal tissue (6.83 +/- 0.08, SD, MDP = -83.5 +/- 3.2 mV), for depolarized Purkinje fibers in infarct preparations during the first hour of superfusion (6.88 +/- 0.11, MDP = -47.8 +/- 11.8 mV), and for partially recovered Purkinje fibers in infarcts averaged over the third to sixth hours of superfusion (6.85 +/- 0.12, MDP = -74.5 +/- 9.6 mV). In 24 mM bicarbonate Tyrode's solution, infarct intracellular pH during both the first hour of superfusion (7.08 +/- 0.13, MDP = -57.6 +/- 15.7 mV) and during the third to sixth hours of superfusion (7.06 +/- 0.15, MDP = -76.5 +/- 9.6 mV) was significantly alkaline (p less than 0.0005) compared with average control pH (6.92 +/- 0.12, MDP = 82.1 +/- 3.7 mV). In 24 mM bicarbonate Tyrode's solution, the intracellular pH did vary with MDP (0.0032 pH units/mV). During superfusion of normal Purkinje fibers with hypoxic Tyrode's solution, intracellular pH acidified by 0.22 pH units as they depolarized. Therefore, intracellular acidification does not seem to be a cause of the depolarization of subendocardial Purkinje cells 24 hours after myocardial infarction.
Purulent pericarditis in children: an analysis of 28 cases
Authors: E. K. Weir, H. S. Joffe
Journal: Thorax (1977)

<b>Weir, E. K., and Joffe, H. S. (1977).</b><i>Thorax</i>, <b>32,</b> 438-443. <b>Purulent pericarditis in children: an analysis of 28 cases.</b> Bacterial pericarditis was diagnosed in 28 children under the age of 13 years during a five-year period at one hospital. The diagnosis was established clinically in 26 cases; in two the condition was first recognized at necropsy. <i>Staphylococcus aureus</i> was isolated in 22 patients, including all 12 with associated osteitis. The other principal primary condition was pneumonia. While 11 patients were treated with antibiotics only, 13 required one or more pericardial aspirations. Acute constrictive pericarditis occurred in two children, both of whom survived pericardiectomy. Of the 26 children with a clinical diagnosis of bacterial pericarditis, eight died in hospital (31%). The pericarditis probably caused death in two cases and was contributory in six. Septic pericarditis tends to occur in children who are already ill because of other foci of bacterial infection and may easily be overlooked, especially in infants. The large numbers reported reflect a high incidence of osteitis in this community. Electrocardiographic and radiological changes are almost always demonstrable, but these are not diagnostic. Antibiotic therapy is imperative and drainage of the pericardium is usually indicated. Bacterial pericarditis is associated with a high mortality. However, while early recognition and treatment is important, death is more often due to the general septicaemia than to pericardial tamponade. In this respect the pericarditis is one indication of the severity of the systemic illness.
The prevalence of seborrhoeic keratoses in an Australian population: does exposure to sunlight play a part in their frequency?
Authors: J.M. YEATMAN, M. KILKENNY, R. MARKS
Journal: British Journal of Dermatology (1997)

Although seborrhoeic keratoses (SKs) appear to be very common, there are very few studies reporting details of age-specific prevalence, distribution or possible cause. We report details on the frequency, nature and distribution of SKs in 100 Australian adults in the age groups 15-25, 26-50, 51-75 and those aged more than 75 years. There was an increase in prevalence of SKs from 12% of 15-25 year olds to 100% of those aged more than 50 years. The median number of lesions in those with them also increased with age from six per person in 15-25 year olds to 69 per person in those aged more than 75 years. There was no difference in prevalence or numbers of lesions/person between males and females. SKs on exposed areas were more often flat and more than 3 mm in diameter than those on the non-exposed areas. There was a higher prevalence of SKs on the exposed areas than non-exposed areas when taking into account the surface area. The data in this study demonstrate an increased frequency of SKs compared with those reported from the United Kingdom recently and from Australasia in the past, a phenomenon paralleling the changing frequency of skin cancer in these populations. This fact, plus the finding that SKs were more common as a function of skin surface area on the exposed areas of the body, suggests that sunlight may play a part in their development in those people who are predisposed to develop them.
Children not immunised for measles
Authors: R A. Benson
Journal: BMJ (1985)

SIR,-Dr Terry Kemple has highlighted the reasons for children not receiving measles immunisation (11 May, p 1395).He comments that "confusion with the pertussis immunisation" was one of the common categories for not accepting measles vaccine.We have recently performed a study on the measles and pertussis immunisation status of all age eligible children born in four calendar months of 1983, as recorded on the district immunisation and vaccination record card.One of the subgroups studied was the measles immunisation status of children who had received the recommended three courses of diphtheria, tetanus, and polio, with or without pertussis.Companison of pertussis and measles immunisation status in children who completed the recommended diphtheria, tetanus, and polio schedule Immunisation status Measles No measles Total Pertussis
WHO, the Global Fund, and medical malpractice in malaria treatment
Authors: Amir Attaran, Karen I Barnes, Christopher Curtis, Umberto d'Alessandro, Caterina I Fanello, Mary R Galinski, Gilbert Kokwaro, Sornchai Looareesuwan, Michael Makanga, Theonest K Mutabingwa, Ambrose Talisuna, Jean François Trape, William M Watkins
Journal: The Lancet (2004)
Clinical trials in idiopathic pulmonary fibrosis: a framework for moving forward
Authors: David J. Lederer
Journal: European Respiratory Journal (2013)

A framework for designing clinical trials in pulmonary fibrosis http://ow.ly/p9tFeIn the current issue of the European Respiratory Journal, RAGHU et al.[1] report the results of the Macitentan USe in Idiopathic Pulmonary Fibrosis Clinical (MUSIC) trial, a randomised placebo-controlled phase 2 clinical trial of macitentan, an oral endothelin antagonist, for biopsy-proven idiopathic pulmonary fibrosis (IPF).With its multicentre enrolment, appropriate allocation concealment, low withdrawal rate and intention-to-treat analysis, this clinical trial exemplifies the state-of-the-art in clinical trial design and conduct in the field of IPF.The authors should indeed be congratulated for accomplishing the difficult task of enrolling and successfully completing a clinical trial in IPF.
Functional magnetic resonance imaging monitoring of pathological changes in rodent livers during hyperoxia and hypercapnia
Authors: Hila Barash, Eitan Gross, Yifat Edrei, Orit Pappo, Gadi Spira, Israel Vlodavsky, Eithan Galun, Idit Matot, Rinat Abramovitch
Journal: Hepatology (2008)

Liver diseases and regeneration are associated with hemodynamic changes denoting pathological alterations. Determining and monitoring physiological and pathological liver changes is essential for diagnostic and therapeutic objectives. Our aim was to determine the feasibility of functional magnetic resonance imaging (fMRI) during hypercapnia and hyperoxia for monitoring liver pathology. Liver fMRI images were acquired in rodents following acute bleeding, partial hepatectomy, and fibrosis. Results were quantitated and confirmed by histology. Changes induced by hyperoxia and hypercapnia following hemorrhage significantly correlated with the percentage of blood loss, reflecting lower liver perfusion and diminished vessel responsiveness to gas saturation. Hepatectomy resulted in an early decline in signal intensity changes due to hyperoxia, suggesting a decrease in liver perfusion and blood content. Following hepatectomy, signal intensity changes due to hypercapnia increased, signifying a change in liver perfusion from a mainly portal to a more arterial source. Two weeks after induction of fibrosis, signal intensity changes due to hypercapnia became much lower and those due to hyperoxia were much higher than those in normal livers, reflecting the increased perfusion due to the inflammatory process as confirmed by histologic analysis. With fibrosis progression, signal intensity changes induced by hypercapnia and hyperoxia were gradually attenuated, indicating structural and functional alterations of the liver vasculature during fibrosis.In various liver pathologies, fMRI response to hypercapnia and hyperoxia is sensitive to changes in liver hemodynamic status involved in hepatic damage or recovery; thus, this technique may offer an additional noninvasive diagnostic tool for evaluation and follow-up of liver diseases by means of examining perfusion-related alterations.
Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Authors: Sudha Seshadri
Journal: JAMA (2010)

Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD).To identify and strengthen additional loci associated with AD and confirm these in an independent sample and to examine the contribution of recently identified genes to AD risk prediction in a 3-stage analysis of new and previously published GWAS on more than 35,000 persons (8371 AD cases).In stage 1, we identified strong genetic associations (P < 10(-3)) in a sample of 3006 AD cases and 14,642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (1367 AD cases [973 incident]) with previously reported results from the Translational Genomics Research Institute and the Mayo AD GWAS. We identified 2708 single-nucleotide polymorphisms (SNPs) with P < 10(-3). In stage 2, we pooled results for these SNPs with the European AD Initiative (2032 cases and 5328 controls) to identify 38 SNPs (10 loci) with P < 10(-5). In stage 3, we combined data for these 10 loci with data from the Genetic and Environmental Risk in AD consortium (3333 cases and 6995 controls) to identify 4 SNPs with P < 1.7x10(-8). These 4 SNPs were replicated in an independent Spanish sample (1140 AD cases and 1209 controls). Genome-wide association analyses were completed in 2007-2008 and the meta-analyses and replication in 2009.Presence of Alzheimer disease.Two loci were identified to have genome-wide significance for the first time: rs744373 near BIN1 (odds ratio [OR],1.13; 95% confidence interval [CI],1.06-1.21 per copy of the minor allele; P = 1.59x10(-11)) and rs597668 near EXOC3L2/BLOC1S3/MARK4 (OR, 1.18; 95% CI, 1.07-1.29; P = 6.45x10(-9)). Associations of these 2 loci plus the previously identified loci CLU and PICALM with AD were confirmed in the Spanish sample (P < .05). However, although CLU and PICALM were confirmed to be associated with AD in this independent sample, they did not improve the ability of a model that included age, sex, and APOE to predict incident AD (improvement in area under the receiver operating characteristic curve from 0.847 to 0.849 in the Rotterdam Study and 0.702 to 0.705 in the Cardiovascular Health Study).Two genetic loci for AD were found for the first time to reach genome-wide statistical significance. These findings were replicated in an independent population. Two recently reported associations were also confirmed. These loci did not improve AD risk prediction. While not clinically useful, they may implicate biological pathways useful for future research.
Atherosclerosis development in apolipoprotein E-null mice deficient for CD69
Authors: Manuel Gómez, Silvia M. Sanz-González, Yafa Naim Abu Nabah, Amalia Lamana, Francisco Sánchez-Madrid, Vicente Andrés
Journal: Cardiovascular Research (2008)

Atherosclerosis is a chronic inflammatory disease regulated by immune mechanisms. CD69 is a cell surface receptor rapidly induced after leukocyte activation at sites of chronic inflammation. Genetic disruption of CD69 in the mouse aggravates collagen-induced arthritis (CIA), and partial depletion of CD69-expressing cells with anti-CD69 monoclonal antibody (mAb) prevents CIA development in wild-type mice, suggesting that this receptor negatively modulates immune and inflammatory responses. It has been recently reported that CD69 is upregulated in a large subset of T cells in atherosclerosis-prone apolipoprotein E-null mice (apoE(-/-)). In this study, we investigated whether altering CD69 function affects atherosclerosis development.We studied native and diet-induced atherosclerosis in apoE(-/-) and doubly deficient apoE(-/-)CD69(-/-) mice and performed expression studies in tissues and primary cells derived from these animals. Plasma cholesterol level was unaffected by CD69 genetic inactivation. Although this genetic manipulation led to an elevated production of interferon gamma and interleukin 10 by activated T cells, apoE(-/-) and apoE(-/-)CD69(-/-) mice fed control and high-fat diet exhibited atheromas of similar size and composition when analysed at different stages of the disease. Likewise, anti-CD69 mAb treatment had no effect on plasma cholesterol and atherosclerosis burden in fat-fed apoE(-/-) mice.In contrast to previous studies highlighting the protective function of CD69 against CIA, an autoimmune inflammatory disease, our results rule out a significant role for CD69 against atherosclerosis in apoE(-/-) mice, an experimental disease model featuring a local inflammatory response triggered and sustained by alterations in lipid homeostasis.
Introduction of Stuart Kornfeld
Authors: Ajit Varki
Journal: Journal of Clinical Investigation (2010)

President Horwitz, Members of the AAP, Ladies and Gentlemen: it is a great pleasure and a very special honor to present the prestigious Kober Medal to Stuart Kornfeld, the very model of the quintessential physician-scientist. Growing up with the ancient traditions of India, I learned the significance of the Guru-Shishya relationship (1), in which the Guru (teacher) is the one who has great knowledge, wisdom, and authority in a certain area and uses it to guide others — and the Shishya is the student or disciple. The principle is that subtle or advanced knowledge is best conveyed through a strong human relationship based on the student’s respect and on the personal instruction by which the student eventually masters the knowledge that the Guru embodies.
Peripheral blood Ia-positive T cells. Increases in certain diseases and after immunization.
Authors: D T Yu, R J Winchester, S M Fu, A Gibofsky, H S Ko, H G Kunkel
Journal: The Journal of Experimental Medicine (1980)

The Ia antigens, usually expressed primarily on B lymphocytes, are found on a small percentage of normal peripheral blood T cells (average 2.6% by fluorescence and 10.8% by rosette assay). Elevated levels up to 40% by both assays were observed in a high proportion of patients with rheumatoid arthritis. Increases also were found in patients with systemic lupus erythematosus and various types of infections. The increases were evident with a specific heteroantiserum, a hybridoma reagent, and DR specific alloantisera. Normal levels were present in multiple sclerosis and an assortment of metabolic and other disorders. A rise in similarly positive T cells occurred in normal individuals after immunization with tetanus toxoid or PPD. The cells primarily involved in all of these instances were small lymphocytes, which stained relatively weakly with the fluorescent reagents and were readily distinguishable from T-cell blasts. They were found to be enriched in isolated T gamma fractions but were also found in other T cells. The accumulated evidence indicated that these cells represent an expansion of one or more subsets of T cells found in normal individuals, and that their level in the peripheral blood may serve as an index of immunological stimulation.
High resolution computed tomography in asthma
Authors: A. N Mclean, M. W Sproule, M. D Cowan, N. C Thomson
Journal: Thorax (1998)

The plain chest radiograph, although useful in the assessment of acute asthma, mainly to exclude unsuspected pneumothorax, collapse or consolidation, 1 2 is unable to demonstrate more subtle changes within the lungs of asthmatic patients.The ability of high resolution computed tomography (HRCT), with a theoretical resolution of 100 µm, to examine small structures within the chest is now being exploited in the investigation of asthma.Recent studies have focused on the visualisation of acute airway responses to bronchoconstrictor and bronchodilator stimuli as well as airway and lung parenchymal changes in chronic asthma. Measurement techniques using HRCTHigh resolution computed tomography has evolved from a combination of improvements in scanner hardware and the software used to reconstruct the images.The single most important feature in improving the spatial resolution is the slice thickness or collimation.In practice this is usually 1-1.5 mm.The second important feature of HRCT is to reconstruct the image using a high spatial frequency algorithm.This decreases contrast resolution and increases the visibility of image noise, but it significantly improves spatial resolution. 3Other features of HRCT are quick scan times to reduce motion artefact, and the use of targeted reconstruction when necessary.These techniques allow selected areas of the lungs to be viewed at close to the inherent maximal spatial resolution of the scan system.The data are manipulated in digital form by sophisticated software to produce the final image.Lung slices can then be examined for evidence of airway and parenchymal lung disease according to recognised criteria.HRCT scanning now has an established role in the investigation of diVuse parenchymal lung disease and bronchiectasis. 4The main disadvantages in the application of HRCT scanning in humans are radiation dose, the complexity of HRCT data analysis for the more complex edge finding algorithms, 5 and technical problems over selection of phantoms for verification.
Pharmacokinetic performance of the nitrendipine intravenous submicron emulsion in rats
Authors: Jibin Guan, Nana Zhao, Yinglei Zhai, Chunxia Chu, Hongming Chen, Tianhong Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2014)

To compare pharmacokinetic behaviors of nitrendipine submicron emulsion with nitrendipine solution following intravenous administration in rats. The plasma concentrations were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry detection (UPLC–MS/MS) through a new validated method. The pharmacokinetic parameters of the nitrendipine submicron emulsion and nitrendipine solution were as follows: AUC0–t 900.76 ± 186.59 versus 687.08 ± 66.24 ng h/ml, Cmax 854.54 ± 159.48 versus 610.59 ± 235.99 ng/ml, t1/2 2.37 ± 1.99 versus 2.80 ± 2.69 h. The relative bioavailability of nitrendipine submicron emulsion to nitrendipine solution was 131.4 ± 11.3%. The developed methods could meet the requirements of bioanalysis. Compared to the solution injection, intravenous submicron emulsion presents higher systematic exposure which can help to improve the therapeutic efficacy.