tbuckley/cabot-search huggingface dataset:
Acetylcholine release from rat atria can be regulated through an alpha 1-adrenergic receptor.
Authors: G T Wetzel, D Goldstein, J H Brown
Journal: Circulation Research (1985)

Isolated superfused rat atria release [3H]acetylcholine when depolarized with 57 mM potassium. The depolarization-induced overflow of [3H]acetylcholine is markedly inhibited by micromolar concentrations of epinephrine and norepinephrine. The alpha 1-selective adrenergic agonist methoxamine also inhibits tritium overflow, but the alpha 2-selective adrenergic agonist clonidine and the beta-adrenergic agonist isoproterenol do not. Prazosin, an selective alpha 1-adrenergic antagonist, blocks adrenergic inhibition of [3H]acetylcholine overflow with a Ki of approximately 0.4 nM. Yohimbine has approximately one-hundredth the potency of prazosin for blocking adrenergic inhibition of [3H]acetylcholine overflow. [3H]Norepinephrine overflow from isolated rat atria is also inhibited by norepinephrine, but this effect is antagonized by yohimbine and not by prazosin. We suggest that the release of acetylcholine from cardiac parasympathetic neurons can be regulated through an alpha 1-adrenergic receptor, and that this mechanism may underly, at least in part, the relative lack of effects of prazosin on heart rate.
<i>ARID5B</i> Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia
Authors: Heng Xu, Cheng Cheng, Meenakshi Devidas, Deqing Pei, Yiping Fan, Wenjian Yang, Geoff Neale, Paul Scheet, Esteban G. Burchard, Dara G. Torgerson, Celeste Eng, Michael Dean, Frederico Antillon, Naomi J. Winick, Paul L. Martin, Cheryl L. Willman, Bruce M. Camitta, Gregory H. Reaman, William L. Carroll, Mignon Loh, William E. Evans, Ching-Hon Pui, Stephen P. Hunger, Mary V. Relling, Jun J. Yang
Journal: Journal of Clinical Oncology (2012)

Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome.We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials.Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10(-20) in whites; P = 1 × 10(-6) in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10(-8)). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics.ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.
Image Fusion Guided Device Closure of Left Ventricle to Right Atrium Shunt
Authors: Elena K. Grant, Anthony Z. Faranesh, Russell R. Cross, Laura J. Olivieri, Karin S. Hamann, Kendall J. O’Brien, Michael S. Hansen, Mary T. Donofrio, Robert J. Lederman, Kanishka Ratnayaka, Michael C. Slack
Journal: Circulation (2015)
PaO2/FiO2 ≤ 250 mm Hg, confusion and uremia predicted more mortalities of severe community-acquired pneumonia with three IDSA/ATS minor criteria
Authors: Qi Guo, Hai-yan Li, Yi-ping Zhou, Ming Li, Xiao-ke Chen, Hui Liu, Hong-lin Peng, Hai-qiong Yu, Xia Chen, Nian Liu, Li-hua Liang, Qing-zhou Zhao, Mei Jiang
Journal: European Respiratory Journal (2012)

Background The Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight. Whether the patients meeting three strongest predictive values have more severity and higher mortality is unclear. The purpose was to determine the speculations. Methods 171 adult severe CAP patients fulfilling three IDSA/ATS minor criteria were reviewed retrospectively. Results Hospital mortality rose sharply from 8.3%, 7.7% and 16.7%, respectively, for patients with other three minor criteria, one of the three strongest predictive values plus other two minor criteria and two of the three strongest predictive values plus another minor criterion to 33.3% for patients meeting the three strongest predictive values [Arterial oxygen pressure/fraction inspired oxygen (PaO2/FiO2) ≤ 250 mm Hg, confusion and uremia].

View this table:

Table 1 Hospital mortality and the patterns of minor criteria





The presence of three strongest predictive values was positively associated with sequential organ failure assessment (SOFA) scores and had a significant increased odds ratio for mortality of 4.500. Conclusions The presence of PaO2/FiO2 ≤ 250 mm Hg, confusion and uremia predicted more severity and mortalities in severe CAP patients meeting three IDSA/ATS minor criteria.
FANCJ Localization by Mismatch Repair Is Vital to Maintain Genomic Integrity after UV Irradiation
Authors: Shawna Guillemette, Amy Branagan, Min Peng, Aashana Dhruva, Orlando D. Schärer, Sharon B. Cantor
Journal: Cancer Research (2013)

Abstract Nucleotide excision repair (NER) is critical for the repair of DNA lesions induced by UV radiation, but its contribution in replicating cells is less clear. Here, we show that dual incision by NER endonucleases, including XPF and XPG, promotes the S-phase accumulation of the BRCA1 and Fanconi anemia–associated DNA helicase FANCJ to sites of UV-induced damage. FANCJ promotes replication protein A phosphorylation and the arrest of DNA synthesis following UV irradiation. Interaction defective mutants of FANCJ reveal that BRCA1 binding is not required for FANCJ localization, whereas interaction with the mismatch repair (MMR) protein MLH1 is essential. Correspondingly, we find that FANCJ, its direct interaction with MLH1, and the MMR protein MSH2 function in a common pathway in response to UV irradiation. FANCJ-deficient cells are not sensitive to killing by UV irradiation, yet we find that DNA mutations are significantly enhanced. Thus, we considered that FANCJ deficiency could be associated with skin cancer. Along these lines, in melanoma we found several somatic mutations in FANCJ, some of which were previously identified in hereditary breast cancer and Fanconi anemia. Given that, mutations in XPF can also lead to Fanconi anemia, we propose collaborations between Fanconi anemia, NER, and MMR are necessary to initiate checkpoint activation in replicating human cells to limit genomic instability. Cancer Res; 74(3); 932–44. ©2013 AACR.
Small joint involvement: a systematic roentgenographic study in rheumatoid arthritis.
Authors: J T Halla, S Fallahi, J G Hardin
Journal: Annals of the Rheumatic Diseases (1986)

Standard hand and foot roentgenograms from 200 consecutively hospitalised patients with definite or classical rheumatoid arthritis (RA) were read for marginal erosions by three independent observers. For each joint or group of joints analysed the degree of symmetry (S = absolute symmetry, U = unilateral, PS = partial symmetry) was determined. The total number of joints affected significantly correlated only with disease duration; symmetry of erosions and number of affected patients were not influenced by seropositivity. Metatarsophalangeal erosions (in 70%) were the most common and were classified as S in 16%, U in 21%, and PS in 63%. Metacarpophalangeal erosions (in 68%) were also common, with a symmetry pattern of S in 19%, U in 21%, and PS in 60%. Proximal finger interphalangeal erosions (in 42%) were unilateral in 42% (S in 8% and PS in 50%). The only site where symmetry was usual (90%) was the wrist, but radiocarpal and intercarpal joints were considered together. Erosions also occurred in about 16% of the finger distal interphalangeal and 28% of the great toe interphalangeal joints. In RA roentgenographic asymmetry is usual and unilateral involvement common.
Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951
Authors: Mathilde C.M. Kouwenhoven, Thierry Gorlia, Johan M. Kros, Ahmed Ibdaih, Alba A. Brandes, Jacolien E.C. Bromberg, Karima Mokhtari, Sjoerd G. van Duinen, Johannes L. Teepen, Pieter Wesseling, Fanny Vandenbos, Wolfgang Grisold, László Sipos, Rene Mirimanoff, Charles J. Vecht, Anouk Allgeier, Denis Lacombe, Martin J. van den Bent
Journal: Neuro-Oncology (2009)

Recent studies have shown that the clinical outcome of anaplastic oligodendroglial tumors is variable, but also that the histological diagnosis is subject to interobserver variation. We investigated whether the assessment of 1p/19q codeletion, polysomy of chromosome 7, epidermal growth factor receptor (EGFR) gene amplification (EGFR(amp)), and loss of chromosome 10 or 10q offers additional prognostic information to the histological diagnosis and would allow molecular subtyping. For this study, we used the clinical data and tumor samples of the patients included in multicenter prospective phase III European Organisation for Research and Treatment of Cancer (EORTC) study 26951 on the effects of adjuvant procarbazine, chloroethyl cyclohexylnitrosourea (lomustine), and vincristine chemotherapy in anaplastic oligodendroglial tumors. Fluorescence in situ hybridization was used to assess copy number aberrations of chromosome 1p, 19q, 7, 10, and 10q and EGFR. Three different analyses were performed: on all included patients based on local pathology diagnosis, on the patients with confirmed anaplastic oligodendroglial tumors on central pathology review, and on this latter group but after excluding anaplastic oligoastrocytoma (AOA) with necrosis. As a reference set for glioblastoma multiforme (GBM), patients from the prospective randomized phase III study on GBM (EORTC 26981) were used as a benchmark. In 257 of 368 patients, central pathology review confirmed the presence of an anaplastic oligodendroglial tumor. Tumors with combined 1p and 19q loss (1p(loss)19q(loss)) were histopathologically diagnosed as anaplastic oligodendroglioma, were more frequently located in the frontal lobe, and had a better outcome. Anaplastic oligodendroglial tumors with EGFR(amp) were more frequently AOA, were more often localized outside the frontal lobe, and had a survival similar to that for GBM. Survival of patients with AOA harboring necrosis was in a similar range as for GBM, while patients with AOA with only endothelial proliferation had better overall survival. In univariate analyses, all molecular factors except loss of 10q were of prognostic significance, but on multivariate analysis a histopathological diagnosis of AOA, necrosis, and 1p(loss)19q(loss) remained independent prognostic factors. AOA tumors with necrosis are to be considered WHO grade IV tumors (GBM). Of all molecular markers analyzed in this study, especially loss of 1p/19q carried prognostic significance, while the others contributed little prognostic value to classical histology.
Differences in motor activation of voluntary and reflex cough in humans
Authors: D Lasserson
Journal: Thorax (2006)

To study motor activation patterns of voluntary and reflex cough adjusted for cough flow rates.Surface electromyography (EMG) and cough flow rate were measured in 10 healthy volunteers. Voluntary cough was assessed for 20 efforts in each quintile of increasing cough flow rate. Reflex cough was assessed for 25 efforts produced by nebulised l-tartaric acid. EMG was recorded over the expiratory (rectus abdominis, obliques, lower intercostals) and accessory (trapezius, pectoralis major, deltoid, latissimus dorsi) muscles. EMG activity, burst duration and onset were compared for each quintile of voluntary cough, and between voluntary and reflex cough matched for cough flow rate.EMG activity and burst duration of expiratory and accessory muscles during voluntary cough increased in proportion to cough flow. Expiratory muscles had longer EMG burst duration (difference 68 ms (95% CI 34 to 102), p<0.01) and earlier onset of EMG activity (difference 44 ms (95% CI 20 to 68), p<0.0001) compared with accessory muscles. EMG activity in all muscles was increased (mean 110.2% v 56.1%, p<0.001) and burst duration (mean 206 ms v 280 ms, p = 0.013) decreased in reflex cough compared with voluntary cough of equal flow rate. There were no differences in EMG onset (difference 8 ms (95% CI 25 to -9) or burst duration (difference 27 ms (95% CI 58 to -4) between expiratory and accessory muscles.Functional organisation of motor activity differs between voluntary and reflex cough. Voluntary cough is characterised by sequential activation whereas reflex cough is associated with early and simultaneous activation of expiratory and accessory muscles.
Expression of CYR61, an Angiogenic Immediate Early Gene, in Arteriosclerosis and Its Regulation by Angiotensin II
Authors: Andres Hilfiker, Denise Hilfiker-Kleiner, Martin Fuchs, Karol Kaminski, Artur Lichtenberg, Hermann-Josef Rothkötter, Bernhard Schieffer, Helmut Drexler
Journal: Circulation (2002)

The renin-angiotensin system is thought to be involved in development and progression of arteriosclerosis, thereby contributing to adverse cardiovascular events. To elucidate the role of angiotensin II (Ang II) at a cellular level, we analyzed the Ang II-induced gene expression profile.Genes induced on Ang II stimulation (10(-7) mol/L, 45 minutes) in rat smooth muscle cells were analyzed by polymerase chain reaction selected subtraction. In addition to known genes, such as interleukin 6, leukemia inhibitory factor, and c-fos, we identified CYR61, an angiogenic immediate early gene. Northern blot analysis revealed a rapid 2.5-fold increase of CYR61 transcript levels by Ang II, peaking at 30 minutes, which was blunted by Ang II type 1 receptor blockade. Exposure of rat aortic rings to Ang II (30 minutes) revealed a 2-fold, and intraperitoneal injection of Ang II (30 minutes) in mice a 3-fold, increase of aortic CYR61 transcripts. In arteriosclerotic aortas of apolipoprotein E-deficient mice, CYR61 transcripts confirmed by in situ hybridization and proteins shown by immunohistochemistry were elevated, whereas they were hardly detectable in wild types. In human carotid atherectomies and arteriosclerotic coronary arteries, immunohistochemical analysis revealed expression of CYR61 within connective tissue in neointima, adventitia, and surrounding small capillaries and blood vessels, colocalized with ACE and Ang II. Normal human arteries showed no significant staining for CYR61.CYR61, an angiogenic factor, is induced by Ang II in vascular cells and tissue. The expression of CYR61, colocalized with Ang II and ACE, in small vessels of human arteriosclerotic lesions is consistent with the notion that the activated renin-angiotensin system may contribute to plaque neovascularization by enhancing regulators of microvessel formation and cell proliferation.
Estrogen receptor α is a major mediator of 17β-estradiol’s atheroprotective effects on lesion size in Apoe–/– mice
Authors: Jeffrey B. Hodgin, John H. Krege, Robert L. Reddick, Kenneth S. Korach, Oliver Smithies, Nobuyo Maeda
Journal: Journal of Clinical Investigation (2001)

The inhibitory effects of estrogen (17β-estradiol) on atherosclerosis have been well documented in numerous animal models, and epidemiological evidence supports this protective effect in humans. The detailed mechanisms for this protection are not understood, but most are thought to be mediated through estrogen receptors (ERs), of which two are known (ERα and ERβ). To investigate the role of ERα in the atheroprotective effect of 17β-estradiol (E2), we ovariectomized female mice that lack apoE (AAee) or lack both apoE and ERα (ααee), and treated half of them with E2 for three months. E2 treatment of ovariectomized AAee females dramatically reduced the size of the lesions as well as their histological complexity. Plasma cholesterol was significantly reduced in this group, although the observed extent of protection by E2 was greater than could be explained solely by the change in lipid levels. In contrast, E2 treatment of ovariectomized ααee females caused minimal reduction in lesion size and no reduction in total plasma cholesterol compared with ααee mice without E2, demonstrating that ERα is a major mediator of the atheroprotective effect of E2. Nevertheless, E2 treatment significantly reduced the complexity of plaques in the ααee females, although not to the same degree as in AAee females, suggesting the existence of ERα-independent atheroprotective effects of E2.
Apolipoprotein E ϵ4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease
Authors: Miia Kivipelto, Eeva-Liisa Helkala, Mikko P. Laakso, Tuomo Hänninen, Merja Hallikainen, Kari Alhainen, Susan Iivonen, Arto Mannermaa, Jaakko Tuomilehto, Aulikki Nissinen, Hilkka Soininen
Journal: Annals of Internal Medicine (2002)

Background: Presence of the apolipoprotein E (apoE) ε4 allele, which is involved in cholesterol metabolism, is the most important genetic risk factor for Alzheimer disease. Elevated midlife values for total cholesterol level and blood pressure have been implicated recently as risk factors for Alzheimer disease. Objective: To study the relative importance and the putative relationship among the apoE ε4 allele, midlife total cholesterol level, and midlife blood pressure as risk factors for late-life Alzheimer disease. Design: Prospective population-based study. Setting: Kuopio and Joensuu, eastern Finland. Participants: Participants were derived from random population surveys from 1972, 1977, 1982, and 1987. A total of 1449 persons (73%), 65 to 79 years of age, participated in the reexamination in 1998 (mean follow-up, 21 years). Measurements: Midlife blood pressure and total cholesterol level, apoE genotype, and development of Alzheimer disease during follow-up. Results: The apoE ε4 allele was an independent risk factor for Alzheimer disease, even after adjustment for midlife vascular risk factors and other confounders (odds ratio, 2.1 [95% CI, 1.1 to 4.1]). Similarly, elevated midlife values for serum total cholesterol level (odds ratio, 2.8 [CI, 1.2 to 6.7]) and systolic blood pressure (odds ratio, 2.6 [CI, 1.1 to 6.6]) were independent risk factors for Alzheimer disease, even after adjustment for apoE genotype and other confounding factors. Conclusions: The association between the apoE ε4 allele and Alzheimer disease does not seem to be mediated by vascular factors. The apoE ε4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for Alzheimer disease. The risk for Alzheimer disease from treatable factors—elevated total cholesterol level and blood pressure—appears to be greater than that from the apoE ε4 allele.
Mesalazine induced interstitial nephritis.
Authors: P J Thuluvath, M Ninkovic, J Calam, M Anderson
Journal: Gut (1994)

5-Aminosalicylic acid (5-ASA) has structural similarities to both phenacetin and aspirin, which are known to cause 9analgesic nephropathy9. Because of the increasing use of 5-ASA, this paper draws attention to two cases of severe interstitial nephritis resulting from 5-ASA and emphasises the importance of monitoring renal functions of patients with inflammatory bowel diseases who are receiving 5-ASA preparations.
Report of Cases of Wood-Alcohol Poisoning
Authors: Edward L. Swadener
Journal: JAMA (1913)

appears a news item headed "Waiters Must Be Healthy," which mentions the safeguards against communicable dis- eases enforced by the Pennsylvania Railroad Company among its employees in dining-car and restaurant service.This is so fully in line with what I have been urging in St. Louis for a number of years that I desire to enlarge somewhat on the topic, as it is of
Mitochondrial Targeting with Antioxidant Peptide SS-31 Prevents Mitochondrial Depolarization, Reduces Islet Cell Apoptosis, Increases Islet Cell Yield, and Improves Posttransplantation Function
Authors: Dolca A. Thomas, Craig Stauffer, Kesheng Zhao, Hua Yang, Vijay K. Sharma, Hazel H. Szeto, Manikkam Suthanthiran
Journal: Journal of the American Society of Nephrology (2006)

Apoptotic cell death is a defined pathway for islet cell demise, and mitochondrial dysfunction contributes to islet cell apoptosis. The hypothesis that the novel peptide D-Arg-2', 6'-dimethyltyrosine-Lys-Phe-NH2 (SS-31), previously shown to target inner mitochondrial membrane and prevent oxidative damage of neuronal cells and other cell types, optimizes pancreatic islet isolation and improves posttransplantation function in recipients with diabetes was investigated. Herein is demonstrated that SS-31 readily penetrates intact mouse islets, preserves mitochondrial polarization, reduces islet cell apoptosis, and increases islet cell yield. Optimization of islet isolation is demonstrable after SS-31 pretreatment of islet (pancreas) donor mice and with the addition of SS-31 to reagents that are used in the isolation of mouse islets. The supplementation of in vitro culture medium with SS-31 reduced islet cell apoptosis and increased the viability of human islets, as ascertained by dual-parameter flow cytometry analysis. In a stringent marginal islet cell mass transplantation model (200 mouse islets transplanted under the renal capsule of syngeneic diabetic mice) and using islets that were derived from old mice (>24 wk), SS-31 treatment was associated with prompt and sustained normoglycemia, whereas the untreated islet graft recipients remained diabetic. Our data suggest a novel strategy to optimize islet isolation and reduce the need for multiple pancreata to achieve insulin independence in the recipient with type 1 diabetes. Because SS-31 was effective with "extended" islet donors, it is hypothesized that the antioxidant SS-31 may serve to increase the pool of eligible organ donors.