tbuckley/cabot-search huggingface dataset:
Factor VIII Concentrate-- Hepatitis
Authors: W. A. Andes
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Ten years ago, Kasper and Kipnis pointed out the likelihood of hepatitis developing in hemophiliacs (1972;221:510). Their study primarily dealt with clinical symptomatology and evaluated the incidents in patients with hemophilia and frequent blood transfusions as well as those who had never received blood products.<sup>1,2</sup>We have had experience with six consecutive patients who had never received factor concentrate and no blood products of any kind for at least five years previously. <h3>Report of Cases.—</h3> We studied the clinical course and serological studies of sixpatients with factor VIII deficiency (Table). Between them, they received commercial factor VIII concentrates from three different manufacturers. Three patients had only a single dose (1,000 to 1,800 antihemophilic factor units). One patient had von Willebrand's disease and the other five had mild to severe factor VIII deficiency. Treatment was given for surgical needs (four) or hemarthroses (two). Patients 3 and
Cytoskeletal Mechanics in Pressure-Overload Cardiac Hypertrophy
Authors: Hirofumi Tagawa, Ning Wang, Takahiro Narishige, Donald E. Ingber, Michael R. Zile, George Cooper
Journal: Circulation Research (1997)

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53±0.77 dyne/cm 2 in the normally loaded LV cardiocytes to 16.46±1.32 dyne/cm 2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97±1.92 poise in the normally loaded LV cardiocytes to 87.85±6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload–hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.
Systemic treatment with liver X receptor agonists raises apolipoprotein E, cholesterol, and amyloid-β peptides in the cerebral spinal fluid of rats
Authors: Sokreine Suon, Jie Zhao, Stephanie A Villarreal, Nikesh Anumula, Mali Liu, Linda M Carangia, John J Renger, Celina V Zerbinatti
Journal: Molecular Neurodegeneration (2010)

Abstract Background Apolipoprotein E (apoE) is a major cholesterol transport protein found in association with brain amyloid from Alzheimer's disease (AD) patients and the ε4 allele of apoE is a genetic risk factor for AD. Previous studies have shown that apoE forms a stable complex with amyloid β (Aβ) peptides in vitro and that the state of apoE lipidation influences the fate of brain Aβ, i.e., lipid poor apoE promotes Aβ aggregation/deposition while fully lipidated apoE favors Aβ degradation/clearance. In the brain, apoE levels and apoE lipidation are regulated by the liver X receptors (LXRs). Results We investigated the hypothesis that increased apoE levels and lipidation induced by LXR agonists facilitates Aβ efflux from the brain to the cerebral spinal fluid (CSF). We also examined if the brain expression of major apoE receptors potentially involved in apoE-mediated Aβ clearance was altered by LXR agonists. ApoE, cholesterol, Aβ40, and Aβ42 levels were all significantly elevated in the CSF of rats after only 3 days of treatment with LXR agonists. A significant reduction in soluble brain Aβ40 levels was also detected after 6 days of LXR agonist treatment. Conclusions Our novel findings suggest that central Aβ lowering caused by LXR agonists appears to involve an apoE/cholesterol-mediated transport of Aβ to the CSF and that differences between the apoE isoforms in mediating this clearance pathway may explain why individuals carrying one or two copies of APOE ε4 have increased risk for AD.
Pacing-Induced Chronic Atrial Fibrillation Impairs Sinus Node Function in Dogs
Authors: Arif Elvan, Kevin Wylie, Douglas P. Zipes
Journal: Circulation (1996)

Background We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. Methods and Results In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 μg/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n=4) or VVI pacing and rapid atrial pacing (n=11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n=4) did not change. Conclusions Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.
Dietary Intake of Antioxidants and Risk of Alzheimer Disease
Authors: Marianne J. Engelhart
Journal: JAMA (2002)

ContextLaboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress.ObjectiveTo determine whether dietary intake of antioxidants is related to risk of Alzheimer disease.Design and SettingThe Rotterdam Study, a population-based, prospective cohort study conducted in the Netherlands.ParticipantsA total of 5395 participants who, at baseline (1990-1993), were aged at least 55 years, free of dementia, and noninstitutionalized and had reliable dietary assessment. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia.Main Outcome MeasuresIncidence of Alzheimer disease, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria, associated with dietary intake of beta carotene, flavonoids, vitamin C, and vitamin E.ResultsAfter a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had Alzheimer disease. When adjustments were made for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease (rate ratios [RRs] per 1-SD increase in intake were 0.82 [95% confidence interval {CI}, 0.68-0.99] and 0.82 [95% CI, 0.66-1.00], respectively). Among current smokers, this relationship was most pronounced (RRs, 0.65 [95% CI, 0.37-1.14] and 0.58 [95% CI, 0.30-1.12], respectively) and also was present for intake of beta carotene (RR, 0.49 [95% CI, 0.27-0.92]) and flavonoids (RR, 0.54 [95% CI, 0.31-0.96]). The associations did not vary by education or apolipoprotein E genotype.ConclusionHigh dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease.
The Impact of Chronic Skin Disease on Daily Life (ISDL): a generic and dermatology-specific health instrument
Authors: A.W.M. Evers, P. Duller, P.C.M. van de Kerkhof, P.G.M. van der Valk, E.M.G.J. de Jong, M.J.P. Gerritsen, E. Otero, E.W.M. Verhoeven, C.M. Verhaak, F.W. Kraaimaat
Journal: British Journal of Dermatology (2007)

Journal Article The Impact of Chronic Skin Disease on Daily Life (ISDL): a generic and dermatology‐specific health instrument Get access A.W.M. Evers, A.W.M. Evers Departments of Medical PsychologyDermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Correspondence: A.W.M. Evers. E‐mail: a.evers@mps.umcn.nl Search for other works by this author on: Oxford Academic Google Scholar P. Duller, P. Duller Departments of Medical PsychologyDermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.C.M. Van De Kerkhof, P.C.M. Van De Kerkhof Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.G.M. Van Der Valk, P.G.M. Van Der Valk Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E.M.G.J. De Jong, E.M.G.J. De Jong Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.J.P. Gerritsen, M.J.P. Gerritsen Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E. Otero, E. Otero Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E.W.M. Verhoeven, E.W.M. Verhoeven Departments of Medical Psychology Search for other works by this author on: Oxford Academic Google Scholar C.M. Verhaak, C.M. Verhaak Departments of Medical Psychology Search for other works by this author on: Oxford Academic Google Scholar F.W. Kraaimaat F.W. Kraaimaat Departments of Medical Psychology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 1, 1 January 2008, Pages 101–108, https://doi.org/10.1111/j.1365-2133.2007.08296.x Published: 01 January 2008
Sequence, organization, and evolution of the A+T region of Drosophila melanogaster mitochondrial DNA.
Authors: D L Lewis, C L Farr, A L Farquhar, L S Kaguni
Journal: Molecular Biology and Evolution (1994)

The long (4.6-kb) A+T region of Drosophila melanogaster mitochondrial DNA has been cloned and sequenced. The A+T region is organized in two large arrays of tandemly repeated DNA sequence elements, with nonrepetitive intervening and flanking sequences comprising only 22% of its length. The first repeat array consists of five repeats of 338-373 bp. The second consists of four intact 464-bp repeats and a fifth partial repeat of 137 bp. Three DNA sequence elements are found to be highly conserved in D. melanogaster and in several Drosophila species with short A+T regions. These include a 300-bp DNA sequence element that overlaps the DNA replication origin and two thymidylate stretches identified on opposite DNA strands. We conclude that the length heterogeneity observed in the A+T regulatory region in mitochondrial DNAs from the genus Drosophila results from the expansion (and contraction) of the number of repeated DNA sequence elements. We also propose that the 300-bp conserved DNA sequence element, in conjunction with another primary sequence determinant, perhaps the adjacent thymidylate stretch, functions in the regulation of mitochondrial DNA replication.
The Health and Cost Benefits of Work Site Health-Promotion Programs
Authors: Ron Z. Goetzel, Ronald J. Ozminkowski
Journal: Annual Review of Public Health (2008)

We review the state of the art in work site health promotion (WHP), focusing on factors that influence the health and productivity of workers. We begin by defining WHP, then review the literature that addresses the business rationale for it, as well as the objections and barriers that may prevent sufficient investment in WHP. Despite methodological limitations in many available studies, the results in the literature suggest that, when properly designed, WHP can increase employees' health and productivity. We describe the characteristics of effective programs including their ability to assess the need for services, attract participants, use behavioral theory as a foundation, incorporate multiple ways to reach people, and make efforts to measure program impact. Promising practices are noted including senior management support for and participation in these programs. A very important challenge is widespread dissemination of information regarding success factors because only ∼7% of employers use all the program components required for successful interventions. The need for more and better science when evaluating program outcomes is highlighted. Federal initiatives that support cost-benefit or cost-effectiveness analyses are stressed, as is the need to invest in healthy work environments, to complement individual based interventions.
RNA Helicase A Is a Downstream Mediator of KIF1Bβ Tumor-Suppressor Function in Neuroblastoma
Authors: Zhi Xiong Chen, Karin Wallis, Stuart M. Fell, Veronica R. Sobrado, Marie C. Hemmer, Daniel Ramsköld, Ulf Hellman, Rickard Sandberg, Rajappa S. Kenchappa, Tommy Martinson, John I. Johnsen, Per Kogner, Susanne Schlisio
Journal: Cancer Discovery (2014)

Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin KIF1B as a 1p36.2 tumor suppressor. However, the mechanism of tumor suppression is unknown. We found that KIF1B isoform β (KIF1Bβ) interacts with RNA helicase A (DHX9), causing nuclear accumulation of DHX9, followed by subsequent induction of the proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma and neuroblastoma arise from neural crest progenitors that compete for growth factors such as nerve growth factor (NGF) during development. KIF1Bβ is required for developmental apoptosis induced by competition for NGF. We show that DHX9 is induced by and required for apoptosis stimulated by NGF deprivation. Moreover, neuroblastomas with chromosomal deletion of 1p36 exhibit loss of KIF1Bβ expression and impaired DHX9 nuclear localization, implicating the loss of DHX9 nuclear activity in neuroblastoma pathogenesis.KIF1Bβ has neuroblastoma tumor-suppressor properties and promotes and requires nuclear-localized DHX9 for its apoptotic function by activating XAF1 expression. Loss of KIF1Bβ alters subcellular localization of DHX9 and diminishes NGF dependence of sympathetic neurons, leading to reduced culling of neural progenitors, and, therefore, might predispose to tumor formation.
Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation.
Authors: S E Lind, D B Smith, P A Janmey, T P Stossel
Journal: Journal of Clinical Investigation (1986)

We determined the plasma kinetics of both actin and complexes of actin with the two high affinity actin-binding proteins of plasma, gelsolin, and vitamin D-binding protein (DBP). Actin is cleared rapidly from the plasma by the liver (half-disappearance time, 0.5 h). Using radiolabeled actin-binding proteins, we found that actin accelerated the clearance of both plasma gelsolin and the vitamin D-binding protein. In separate experiments we found that DBP-actin complexes were cleared more quickly than gelsolin-actin complexes, at a rate comparable to the clearance of actin from the blood. A low affinity interaction (dissociation constant, 2.9 X 10(-4) M) between actin and fibronectin was found, suggesting that little actin will bind to fibronectin in plasma. We conclude that while plasma gelsolin and DBP may both clear actin from the circulation, DBP appears to play a more important role. By so doing, DBP may conserve the filament-severing activity of plasma gelsolin.
Eradicating <i>Helicobacter pylori</i> reduces hypergastrinaemia during long term omeprazole treatment
Authors: A El-Nujumi, C Williams, J E Ardill, K Oien, K E L McColl
Journal: Gut (1998)

Background —Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man. Aims —To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment. Methods —Patients with H pylori were randomised to treatment with either anti- H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment. Results —In the patients randomised to anti- H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti- H pylori /symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26–86) at initial presentation and increased to 64 ng/l (range 29–271) after seven months omeprazole, representing a median increase of 68% (p&lt;0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17–226) and was unchanged after seven months omeprazole at 38 ng/l (range 17–95). Conclusion —Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long term proton pump inhibitor treatment.
Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells
Authors: Kibem Kim, Andrew Skora, Zhaobo Li, Ada Tam, Luis Diaz, Nickolas Papadopolous, Lee Blosser, Kenneth Kinzler, Bert Vogelstein, Shibin Zhou
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Recent clinical trials have shown highly promising responses in a subset of patients treated with immune checkpoint inhibitory anti-programmed cell death-1, anti-programmed cell death ligand-1 (PD-1), and anti-cytotoxic T-lymphocyte-associated antigen-4 antibodies (CTLA-4) [[1][1
The kidney in sarcoidosis.
Authors: F J Casella, M Allon
Journal: Journal of the American Society of Nephrology (1993)

Sarcoidosis has been associated with a wide spectrum of renal manifestations, including disordered calcium metabolism, nephrocalcinosis, nephrolithiasis, granulomatous interstitial nephritis, and glomerulonephritis. In some patients, two or more manifestations of renal sarcoidosis may coexist. The case of a young patient with sarcoidosis who presented with hypercalcemia and acute renal failure is discussed. Despite normalization of the serum calcium with intravenous fluids and corticosteroids, his renal insufficiency persisted. A diagnostic renal biopsy was performed to determine the etiology of his renal failure and was helpful in the selection of optimal medical therapy.
HLA-DRB1* alleles and symptoms associated with Heerfordt's syndrome in sarcoidosis
Authors: P. Darlington, L. Tallstedt, L. Padyukov, I. Kockum, K. Cederlund, A. Eklund, J. Grunewald
Journal: European Respiratory Journal (2011)

Heerfordt's syndrome (HS) consists in its complete form of uveitis, parotid or salivary gland enlargement and cranial nerve palsy. The objective of the present study was to analyse if there are also links between HLA-DRB1* alleles and HS, as it is a specific phenotype of sarcoidosis. 1,000 patients with sarcoidosis, out of whom 83 had symptoms associated with HS, were included in the study together with a group of 2,000 healthy individuals from the same population, matched for sex and age. HLA-DRB1* allelic groups were determined for all individuals, and comparisons were made between different disease subgroups and between patients and healthy controls. We found that the HLA-DRB1*04 allele was overrepresented in patients with symptoms associated with HS. 83 (8.3%) of all patients had one or more of the symptoms and 46 (55%) of them were HLA-DRB1*04 positive. 44 (55%) of the patients with ocular sarcoidosis, i.e. the most common symptom associated with HS, were HLA-DRB1*04 positive, compared with 35.9% of healthy controls (p=0.0008), and only 26.6% of the whole group of sarcoidosis patients (p<0.0001). HLA-DRB1*04 seems to protect against overall sarcoidosis but appears to be a significant risk factor for ocular sarcoidosis as well as for other manifestations associated with HS.
The P53 “Knockout”: Gone But Not Forgotten
Authors: David Carbone
Journal: Hepatology (1992)

ABSTRACT Mutations in the p53 tumour–suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
Neighborhoods, Obesity, and Diabetes — A Randomized Social Experiment
Authors: Jens Ludwig, Lisa Sanbonmatsu, Lisa Gennetian, Emma Adam, Greg J. Duncan, Lawrence F. Katz, Ronald C. Kessler, Jeffrey R. Kling, Stacy Tessler Lindau, Robert C. Whitaker, Thomas W. McDade
Journal: New England Journal of Medicine (2011)

The question of whether neighborhood environment contributes directly to the development of obesity and diabetes remains unresolved. The study reported on here uses data from a social experiment to assess the association of randomly assigned variation in neighborhood conditions with obesity and diabetes.