tbuckley/cabot-search huggingface dataset:
Recovery of Methacholine Responsiveness after End of Exposure in Occupational Asthma
Authors: Jean-Luc Malo, Heberto Ghezzo
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Recent data suggest that responsiveness to methacholine continues to improve 2 and more years after cessation of exposure to agents causing occupational asthma (OA). The goal of this study was to characterize further the curve of improvement to methacholine responsiveness in subjects with OA. Eighty subjects with confirmed OA who had at least two assessments of a provocative concentration of histamine causing a 20% drop in FEV(1) (PC(20)) and were seen for at least 2 years after cessation of exposure. The shape of recovery of PC(20) was assessed by CARMA (James K. Lindsey, Liège, Belgium) analysis. Slopes of recovery were compared in the first 2.5 years in 55 subjects and from 2.5 years until the end of observation in 56 subjects. Recovery curves showed progressive improvements in PC(20) significantly influenced by time lapse since end of exposure, sex, baseline PC(20), and FEV(1). The slopes of recovery were significantly different from zero both for the first 2.5 years after cessation of exposure (0.27 +/- 0.05 SEM natural logarithm of PC(20) per year) and later (0.09 +/- 0.008 SEM natural logarithm of PC(20) per year), with the slope significantly steeper for the first 2.5 years. This study shows that improvement in responsiveness to methacholine continues for years after cessation of exposure but that the improvement is more rapid in the first 2.5 years.
Familial Xy Gonadal Dysgenesis
Authors: William H. Sternberg, David L. Barclay, H. Warner Kloepfer
Journal: New England Journal of Medicine (1968)

XY pure gonadal dysgenesis has been found in three phenotypic females in three different sibships in the same family. The proposita, a maternal cousin and a maternal aunt are similarly affected. They are all of normal stature, possess uteri, but lack spontaneous secondary sexual development. There are no signs of Turner's syndrome. All are sex chromatin negative and have a normal 46 XY male karyotype. Streak gonads were surgically removed from the proposita, and one contained a microscopic focus of sex-cord tumor. Since the disorder is extremely rare and occurred in three sibships of a single family it is most probably gene determined. If so, the abnormal gene or genes are maternally transmitted and probably either X-linked or carried on an autosome and expressed only in chromosomal males. Whether the abnormal genes directly suppress testis-determining loci on the Y chromosome or block some early stage of testicular morphogenesis is not known.
Acute massive intestinal bleeding caused by hookworm
Authors: H. de la Riva
Journal: JAMA (1981)

AMONG the causes of acute gastrointestinal (GI) tract bleeding, hookworm infestation is not usually considered. Chronic occult bleeding is well known, but acute hemorrhage is rarely recorded.<sup>1-5</sup>We describe a patient who had a massive intestinal hemorrhage. <h3>Report of a Case</h3> A 19-year-old man was admitted because of more than 20 episodes of melena and hematochezia in the preceding 12 hours. Physical examination disclosed pallor, cold skin, blood pressure of 80/50 mm Hg, and pulse rate of 110 per minute. A blood test showed the following values: hemoglobin, 5.2 g/dL; hematocrit, 19%; reticulocytes, 10%; leukocytes, 33,000/cu mm; neutrophils, 58%; eosinophils, 33%; basophils, 1%; and lymphocytes, 8%. Upper GI tract endoscopy, sigmoidoscopy, and small-bowel and barium enema x-ray films were normal. Mesenteric angiography showed a possible bleeding zone in the jejunum. Three liters of whole blood was administered and a laparotomy performed on the fourth day. Complete examination did not
Kinking of the aorta with calcific aortic valve stenosis.
Authors: T Izukawa
Journal: Thorax (1966)

Kinking or buckling of the aorta is uncommon.The combination of a kinked aorta with severe calcific aortic valve stenosis is very unusual.The importance of recognizing kinking of the aorta lies in the fact that it can mimic other more serious conditions, such as a mediastinal tumour, aortic aneurysm, or coarctation.One of the earliest cases reported was diagnosed as Hodgkin's disease of the superior mediastinal glands; radiotherapy did not reduce the mass.Thoracotomy revealed the sharply kinked aorta, and the apex of the kink was sited at the insertion of a short patent ductus arteriosus.The aorta was not narrowed (Souders,
A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.
Authors: C Ponticelli, P Altieri, F Scolari, P Passerini, D Roccatello, B Cesana, P Melis, B Valzorio, M Sasdelli, S Pasquali, C Pozzi, G Piccoli, A Lupo, S Segagni, F Antonucci, M Dugo, M Minari, A Scalia, L Pedrini, G Pisano, C Grassi, M Farina, R Bellazzi
Journal: Journal of the American Society of Nephrology (1998)

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.
Early exercise after coronary stenting is safe
Authors: Marco Roffi, Peter Wenaweser, Stephan Windecker, Haresh Mehta, Franz R. Eberli, Christian Seiler, Martin Fleisch, Ali Garachemani, Giovanni B. Pedrazzini, Otto M. Hess, Bernhard Meier
Journal: Journal of the American College of Cardiology (2003)
Localized periorbital edema induced by aspirin
Authors: Y. Katz, N. Goldberg, S. Kivity
Journal: Allergy (1993)

We documented localized periorbital edema in two patients with aspirin sensitivity without underlying chronic urticaria. The reaction developed 30 min after ingestion of 62.5 and 125 mg of aspirin, respectively. No systemic symptoms were observed. Other NSAIDs did not induce symptoms. These patients were able to tolerate doses of aspirin after pretreatment with terfenadine. These observations suggest that histamine plays a central role in aspirin‐induced skin reaction. Despite the fact that terfenadine blocks the drug‐induced reaction, this protocol should be used with caution and only where there is no feasible alternative to aspirin.
Injuries from Fireworks
Authors: D. Jackson
Journal: BMJ (1961)

In 1604, the year after James I came to the throne, a plot was hatched to destroy the King and his Govern- ment by blowing up the Houses of Parliament.Guy Fawkes, who was the tool of more influential people, was chosen for the dangerous task of setting fire to the gunpowder when Parliament opened on November 5, 1605.But the plot miscarried.Fawkes was arrested as he went to take up his position in the cellars the night before, and the other conspirators were killed or taken prisoner.
Complete remission in acute promyelocytic leukemia despite the persistence of the 15;17 translocation
Authors: Paul J. Wallace
Journal: American Journal of Hematology (1989)

Abstract Acute promyelocytic leukemia (APL) is a morphologically distinct subtype of acute non‐lymphocytic leukemia (ANLL) characterized cytogenetically by the presence of a trans‐location between chromosomes 15 and 17 (t(15;17)). In contrast to other subtypes of ANLL, morphologic examination of the bone marrow in the early postinduction period fails to identify patients adequately who have a high likelihood of entering remission. Remission has frequently been achieved in APL despite the failure to attain marrow aplasia or eliminate dysplastic progranulocytes after initial induction chemotherapy. In a patient with APL who failed to achieve cytoreduction after a single course of induction chemotherapy, serial cytogenetic studies demonstrated persistence of metaphases with the t(15;17) up to 23 days after induction. However, complete morphologic and cytogenetic remission was subsequently attained by day 29 without further therapy. In APL remission may occur even when induction therapy fails to achieve marrow aplasia or to eradicate replicative cells with abnormal karyotype promptly. In order to avoid excessive exposure to toxic therapy, new strategies may be necessary to identify, early in treatment, patients with APL who will require only one course of induction chemotherapy to enter remission successfully.
Selective Inhibition of Cyclooxygenase-2 Enhances Platelet Adhesion in Hamster Arterioles In Vivo
Authors: Martin A. Buerkle, Selim Lehrer, Hae-Young Sohn, Peter Conzen, Ulrich Pohl, Florian Krötz
Journal: Circulation (2004)

Selective inhibitors of cyclooxygenase-2 (Cox-2) are reported to cause cardiovascular side effects in patients at risk. However, direct proof of prothrombotic effects of these drugs is lacking. We investigated in the microcirculation in vivo whether selective inhibition of Cox-2 induces platelet activation.The behavior of fluorescence-labeled human platelets was studied in hamster arterioles (dorsal skinfold chamber) by intravital microscopy. Transient platelet-vessel wall interactions (PVWIs), firm platelet adhesion to the vessel wall, and vessel occlusion after FeCl3-induced wall injury were analyzed as platelet activation parameters. In vitro experiments in human umbilical vein endothelial cells (HUVECs) were performed to assess specific effects of Cox-2 inhibition on platelet adhesion under shear stress (16 dyn/cm2) and on endothelial release of 6-ketoprostaglandin (PG) F(1alpha). Selective inhibition of Cox-2 (NS-398, 0.5 mg/kg) increased platelet adhesion to the vessel wall in vivo (11.9+/-3.9 platelets/mm2; controls, 1.4+/-1.4 platelets/mm2, P<0.05) and platelet adhesion after ADP stimulation in vitro. PVWIs were significantly enhanced in NS-398-treated animals, which were reduced by platelet pretreatment with aspirin (5 mg/kg) or iloprost (1 nmol/L). Inhibition of Cox-2 reduced levels of 6-keto-PGF1alpha in vivo and in HUVEC supernatants. Time to occlusion after vessel wall injury was significantly shortened by NS-398 (125.4+/-13.6 seconds in NS-398-treated animals versus 270.8+/-46 seconds in controls; P<0.01).Selective inhibition of Cox-2 reduces 6-keto-PGF(1alpha) endothelial release, increases PVWIs, and increases firm platelet adhesion in hamster arterioles. Moreover, it leads to faster occlusion of damaged microvessels. Thus, selective inhibition of Cox-2 may trigger thrombotic events by diminishing the antiplatelet properties of the endothelium.
DIAGNOSTIC ACCURACY OF BASAL STENOSIS RESISTANCE INDEX FOR MYOCARDIAL ISCHEMIA IDENTIFIED BY FRACTIONAL FLOW RESERVE AND IMPLICATIONS OF STENOSIS RESISTANCE INDEX DETERMINED AT SUB–MAXIMALLY ELEVATED CORONARY FLOW RATES
Authors: Tim van de Hoef, Froukje Nolte, Peter Damman, Ronak Delewi, Mariëlla ECJ Hassell, Steven Chamuleau, Michiel Voskuil, José Henriques, Robbert de Winter, Jan Tijssen, Maria Siebes, Martijn Meuwissen, Jos AE Spaan, Jan Piek
Journal: Journal of the American College of Cardiology (2013)
Asymmetric Functional Divergence of Duplicate Genes in Yeast
Authors: Andreas Wagner
Journal: Molecular Biology and Evolution (2002)

Most duplicate genes are eliminated from a genome shortly after duplication, but those that remain are an important source of biochemical diversity. Here, I present evidence from genome-scale protein-protein interaction data, microarray expression data, and large-scale gene knockout data that this diversification is often asymmetrical: one duplicate usually shows significantly more molecular or genetic interactions than the other. I propose a model that can explain this divergence pattern if asymmetrically diverging duplicate gene pairs show increased robustness to deleterious mutations.
Bestrophin-2 mediates bicarbonate transport by goblet cells in mouse colon
Authors: Kuai Yu, Rafael Lujan, Alan Marmorstein, Sherif Gabriel, H. Criss Hartzell
Journal: Journal of Clinical Investigation (2010)

Anion transport by the colonic mucosa maintains the hydration and pH of the colonic lumen, and its disruption causes a variety of diarrheal diseases. Cholinergic agonists raise cytosolic Ca2+ levels and stimulate anion secretion, but the mechanisms underlying this effect remain unclear. Cholinergic stimulation of anion secretion may occur via activation of Ca2+-activated Cl- channels (CaCCs) or an increase in the Cl- driving force through CFTR after activation of Ca2+-dependent K+ channels. Here we investigated the role of a candidate CaCC protein, bestrophin-2 (Best2), using Best2-/- mice. Cholinergic stimulation of anion current was greatly reduced in Best2-/- mice, consistent with our proposed role for Best2 as a CaCC. However, immunostaining revealed Best2 localized to the basolateral membrane of mucin-secreting colonic goblet cells, not the apical membrane of Cl--secreting enterocytes. In addition, in the absence of HCO3-, cholinergic-activated current was identical in control and Best2-/- tissue preparations, which suggests that most of the Best2 current was carried by HCO3-. These data delineate an alternative model of cholinergic regulation of colonic anion secretion in which goblet cells play a critical role in HCO3- homeostasis. We therefore propose that Best2 is a HCO3- channel that works in concert with a Cl:HCO3- exchanger in the apical membrane to affect transcellular HCO3- transport. Furthermore, previous models implicating CFTR in cholinergic Cl- secretion may be explained by substantial downregulation of Best2 in Cftr-/- mice.
FASL –844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer
Authors: Tong Sun, Yifeng Zhou, Hua Li, Xiaohong Han, Yuankai Shi, Li Wang, Xiaoping Miao, Wen Tan, Dan Zhao, Xuemei Zhang, Yongli Guo, Dongxin Lin
Journal: The Journal of Experimental Medicine (2005)

The FAS receptor–ligand system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumor-immune escape and carcinogenesis. We have recently demonstrated (Sun, T., X. Miao, X. Zhang, W. Tan, P. Xiong, and D. Lin. 2004. J. Natl. Cancer Inst. 96:1030–1036; Zhang, X., X. Miao, T. Sun, W. Tan, S. Qu, P. Xiong, Y. Zhou, and D. Lin. 2005. J. Med. Genet. 42:479–484) that functional polymorphisms in FAS and FAS ligand (FASL) are associated with susceptibility to lung cancer and esophageal cancer; however, the mechanisms underlying this association have not been elucidated. We show that the FAS –1377G, FAS –670A, and FASL –844T variants are expressed more highly on ex vivo–stimulated T cells than the FAS –1377A, FAS –670G, and FASL –844C variants. Moreover, activation-induced cell death (AICD) of T cells carrying the FASL –844C allele was increased. We also found a threefold increased risk of cervical cancer among subjects with the FASL –844CC genotype compared with those with the –844TT genotype in a case-control study in Chinese women. Together, these observations suggest that genetic polymorphisms in the FAS–FASL pathway confer host susceptibility to cervical cancers, which might be caused by immune escape of tumor cells because of enhanced AICD of tumor-specific T cells.
Expression of Thrombospondin-1 in Resected Colorectal Liver Metastases Predicts Poor Prognosis
Authors: Christopher D. Sutton, Kenneth O'Byrne, Jonathan C. Goddard, Leslie-Jayne Marshall, Louise Jones, Giuseppe Garcea, Ashley R. Dennison, Graham Poston, David M. Lloyd, David P. Berry
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of this study was to examine the expression and prognostic relevance of thrombospondin-1 (TSP-1) in tumor biopsies taken from a consecutive series of liver resections done at the University Hospitals of Leicester and the Royal Liverpool Hospital. Experimental Design: Patients having undergone a liver resection for colorectal liver metastases at our institutions between 1993 and 1999 inclusive were eligible. Inclusion criteria were curative intent, sufficient tumor biopsy, and patient follow-up data. One hundred eighty-two patients were considered in this study. Standard immunohistochemical techniques were used to study the expression of TSP-1 in 5-μm tumor sections from paraffin-embedded tissue blocks. TSP-1 was correlated with survival using the Kaplan-Meier method and log-rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. Results: One hundred eighty-two patients (male, n = 122 and female, n = 60) ages between 25 and 81 years (mean, 61 years) were included. TSP-1 was expressed around blood vessels (n = 45, 25%) or in the stroma (n = 59, 33%). No expression was detected in the remaining tumors. TSP-1 significantly correlated with poor survival on univariate (P = 0.01 for perivascular expression and P = 0.03 for stromal expression) and multivariate analysis (P = 0.01 for perivascular expression). Conclusion: TSP-1 is a negatively prognostic factor for survival in resected colorectal liver metastases.
DRD2 Ser311/Cys311 polymorphism in schizophrenia
Authors: S. Nanko, M. Hattori, Xy Dai, R. Fukuda, H. Kazamatsuri, MargaretA. Piggott, ElaineK. Perry, lanG. McKeith, Elizabeth Marshall, RobertH. Perry, P. Asherson, N. Williams, E. Roberts, M. McGuffin, M. Owen, S. Shaikh, D. Collier, M. Arranz, D. Ball, M. Gill, R. Kerwin
Journal: The Lancet (1994)
DIETARY VITAMIN A AND RISK OF CANCER IN THE WESTERN ELECTRIC STUDY
Authors: RichardB. Shekelle, Shuguey Liu, WillamJ. Raynor, Mark Lepper, Carol Maliza, ArthurH. Rossof, Oglesby Paul, AnneMacmillan Shryock, Jeremiah Stamler
Journal: The Lancet (1981)
Chronic intermittent hypoxia induces features of non alcoholic fatty liver disease (NAFLD) and modifies adipose tissue characteristics in lean mice
Authors: Judith Aron-Wisnewsky, Emmanuelle Gras, Amandine Thomas, Diane Godin-Ribuot, Karine Clement, Jean-Louis Pepin
Journal: European Respiratory Journal (2014)

Introduction: In human obesity, chronic intermittent hypoxia (CIH) due to obstructive sleep apnoea induces NAFLD exacerbation. Whether this remains true in non-obese OSA is still debated. By contrast, CIH induced no adipose tissue (AT) histological modifications in morbidly obese. We aimed to evaluate the effect of a 14 days CIH on both liver, subcutaneous and epididymal AT in lean mice. Methods: 16 mice fed a chow-diet and were submitted to either normoxia or 8 hours of CIH.

Methods: After 14 days of exposure, expression of extra-cellular matrix, inflammatory and lipogenesis genes with PCR and immunohistological analysis were performed on liver and the two AT depots.

Results: In liver, CIH induced a significantly increased expression of gene involved in lipogenesis (ACC, SREBP1c, FAS), fibrosis (Coll1, Coll3, TGFβ), and inflammation (TNFα, IL1β) compared to mice on normoxia (at least two-fold ratio). However, this short CIH duration did not translate into histological lesions. Although mice submitted to CIH were significantly lighter than mice on normoxia, their epididymal AT was two-fold heavier in terms of percentage of total body weight. Furthermore, adipocyte size was increased in CIH along with increased leptin gene expression in epididymal AT (p=0.008). No difference was observed in inflammatory or extra-cellular matrix gene expression.

Conclusion: In lean mice, a short duration of CIH (14 days) already induces the features of NAFLD at the gene expression levels that do not yet translate into histological lesions. Furthermore, CIH also seems to impact on corpulence and adipose tissue characteristics.
Characterisation of activated lymphocytes in the peripheral blood of patients with rheumatoid arthritis.
Authors: S.D Carter, P.A Bacon, N.D Hall
Journal: Annals of the Rheumatic Diseases (1981)

The extent and nature of lymphocyte activation in the circulation in rheumatoid arthritis (RA) was investigated. Peripheral blood lymphocytes (PBL) from RA patients and healthy controls were separated into a number of discrete fractions by density in discontinuous Ficoll density gradients. Low density (activated) lymphocytes were found at significantly higher levels in RA, particularly in patients with clinically active disease. Conversely, patients with clinically inactive RA had normal levels of activated lymphocytes. Lymphocyte populations within the ficoll gradient fractions were detected by E rosettes, staining for surface Ig, and by different avidities of EA binding. The activated population in RA was shown to be relatively depleted of T cells, enriched in surface Ig-bearing lymphocytes, and depleted of lymphocytes with high avidity EA binding. The evidence suggests that many of the activated PBL in RA are B blasts.
Re-analysis of application of haemoclips for non-variceal upper gastrointestinal bleeding data.
Authors: Lin Hj
Journal: Gut (2008)

We read with interest the article by Sung et al ( Gut 2007; 56 :1364–73). In this study, Sung et al retrospectively reviewed 15 trials with non-variceal upper gastrointestinal bleeding, and compared subjects who received haemoclip application, thermocoagulations or injections. Application of haemoclips is superior to injection alone but comparable with thermocoagulation in achieving haemostasis.

There is one key point in this study that needs to be discussed. There is one technical problem regarding the application of haemoclips. The haemoclip must meet …