tbuckley/cabot-search huggingface dataset:
Immunopathological aspects of immunoglobulin A nephropathy and other mesangial proliferative glomerulonephritides.
Authors: F P Schena, L Gesualdo, V Montinaro
Journal: Journal of the American Society of Nephrology (1992)

Immunoglobulin A nephropathy (IgAN) is an immune complex (IC) glomerulonephritis (GN) that represents one of the most common forms of primary glomerular disease. Proliferation of mesangial cells and the increase of mesangial matrix are histological hallmarks of mesangioproliferative GN. Increased serum levels of IgA, polymeric IgA, IgA rheumatoid factor, IgA-IC, and spontaneous or pokeweed mitogen-induced production of IgA by peripheral blood mononuclear cells are major humoral immune alterations reported in IgAN. Recently, we focused on the role of cytokines and growth factors in the mediation of glomerular injury. Platelet-derived growth factor, transforming growth factor beta, interleukin (IL)-1 and IL-6 are expressed by and act on mesangial cells. Increased expression of platelet-derived growth factor was found in both an active model of IgAN and in renal biopsies of patients with proliferative GN. A strict correlation between increased expression of B-chain mRNA and mesangial proliferation was found. Cytokines such as IL-1, interferon gamma, and IL-6, released by infiltrating mononuclear cells or produced locally by mesangial cells, affect the glomerular response to IgA-IC. In a passive murine experimental model of IgAN, IL-1 and interferon gamma increased mesangial hypercellularity, whereas IL-6 was highly pathogenic when associated to IL-1. In conclusion, classical immunological mechanisms in mesangial GN could interact with other pathways involving cytokines and growth factors in the progression of glomerular injury.
P249 Obstructive sleep apnea out patient screening study: Abstract P249 Table 1.
Authors: E Rasul, A Patel, A Khan, A Haridas, S Smith, A Reddy, H Patel
Journal: Thorax (2013)

<h3>Introduction</h3> Obstructive sleep apnea (OSA) is increasingly being recognised as an important health care issue. Incidence and prevalence of OSA are gradually increasing worldwide. There is increasing evidence that OSA is being considered as an independent risk factor for hypertension, diabetes mellitus, cardiovascular diseases and stroke, leading to increased cardio-metabolic morbidity and mortality. Many questionnaires are available for OSA screening. Many studies done in peri-operative population showed that the STOP-BANG questionnaire (Snoring, Tiredness, Observed apnea, high blood Pressure, BMI &gt; 30, Age &gt; 50, neck Circumference, Gender male) is the simplest, with a high positive predictive value. A sleep study is advised for anyone who has 3 or more positive variables from STOP-BANG. The purpose of our study was to analyse the STOP-BANG questionnaire’s validity for OSA screening in the primary care setting. Currently, there is no available screening tool for OSA in outpatient setting. <h3>Methods</h3> Study involved a retrospective chart analysis from outpatient clinics. Patients from neurology and sleep clinic were excluded. Electronic medical record was used for patient selection. We randomly selected the first 400 patients who had 3 out of 8 variables from STOP-BANG. <h3>Results</h3> Out of 400 selected patients, 124 (31%) had 3 variables, 180 (45%) had 4 variables, 54 (13.5%) had 5 variables, 32 (8%) had 6 variables &amp; 10 (2.5%) had 7 variables. Neck circumference was not documented in the charts so the 8<sup>th</sup> variable was not available. Out of 400 patients with 3–7 positive STOP-BANG variables, only 25% (100/400) received a sleep study and 73% (73/100) were diagnosed with OSA. <h3>Conclusion</h3> Primary care physicians should screen all high-risk patients using STOP-BANG questionnaire. STOP-BANG is an affirmative screening tool in peri-operative population and our study indicates that it can also be an efficient screening questionnaire in primary care clinics. However more studies are needed to testify it. OSA is an easily diagnosable condition but often overlooked. Early recognition and treatment of obstructive sleep apnea may prevent adverse health consequences.
Prediagnostic Level of Serum Retinol in Relation to Reduced Risk of Hepatocellular Carcinoma
Authors: Jian-Min Yuan, Yu-Tang Gao, Choon-Nam Ong, Ronald K. Ross, Mimi C. Yu
Journal: JNCI Journal of the National Cancer Institute (2006)

Retinol and its derivatives (retinoids), which have antioxidant activity and promote cell differentiation, may protect against the development of hepatocellular carcinoma (HCC) by controlling hepatocellular differentiation and reducing inflammatory responses.We examined prospectively the relationship between prediagnostic serum concentrations of retinol, alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; and selenium and the risk of developing HCC among 213 patients with HCC and 1087 matched control subjects from a cohort of 18,244 men in Shanghai, China, who were monitored from 1986 through 2001. Odds ratios (ORs) and 95% confidence intervals (CIs) for men by quartile of serum concentrations of micronutrients were estimated by using logistic regression with adjustment for cigarette smoking status, alcohol intake, self-reported history of physician-diagnosed hepatitis or liver cirrhosis at recruitment, and seropositivity for hepatitis B surface antigen (HBsAg). All statistical tests were two-sided.Men with high prediagnostic serum retinol levels had a lower risk of HCC than men in the lowest quartile (Q2 versus Q1, OR = 0.37, 95% CI = 0.22 to 0.61; Q3 versus Q1, OR = 0.30, 95% CI = 0.17 to 0.50; and Q4 versus Q1, OR = 0.13, 95% CI = 0.06 to 0.26; Ptrend < .001). A statistically significant interaction was observed between retinol and HBsAg seropositivity on HCC risk; HBsAg-positive men in the lowest tertile of retinol had a greater than 70-fold higher risk (OR = 72.7, 95% CI = 31.6 to 167.4) of HCC than HBsAg-negative men in the highest tertile of retinol (Pinteraction = .018). No independent effect of serum levels of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; or selenium on HCC risk were observed.High prediagnostic serum level of retinol is associated with a decreased risk of HCC in this population.
Neoexpression of Lewis Y antigen is a sensitive phenotypic change of the damaged intrahepatic bile ducts
Authors: Motoko Sasaki, Naoko Kono, Yasuni Nakanuma
Journal: Hepatology (1994)

We examined the expression of Lewis antigens, particularly Lewis Y, on the intrahepatic biliary epithelial cells in normal livers and various hepatobiliary diseases with immunohistochemical and immunoelectron microscopic methods. In normal livers, Lewis Y was consistently and generally negative in the bile ductules and small bile ducts, respectively. This antigen was frequently and strongly expressed on these ducts and ductules showing variable pathological changes such as necroinflammation and proliferation in a majority of hepatobiliary diseases independent on their etiology, whereas a majority of normal-appearing bile ducts and ductules in these pathological conditions were negative. Immunoelectron microscopically, gold particles suggesting the presence of Lewis Y were demonstrated on microvilli facing the biliary lumen, lateral cell membranes, secretory granules and Golgi apparatus of abnormal biliary epithelial cells in various hepatobiliary diseases. These data suggest that neoexpression of Lewis Y antigen is a highly sensitive, nonspecific phenotypic change of carbohydrate residues occurring in the abnormal biliary epithelial cells in various hepatobiliary diseases.
Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the CD4 and CD2 coreceptors.
Authors: S Wee, G L Schieven, J M Kirihara, T T Tsu, J A Ledbetter, A Aruffo
Journal: The Journal of Experimental Medicine (1993)

When T cells are activated via the T cell receptor (TCR) complex a number of cellular substrates, including some cell surface proteins, become phosphorylated on tyrosine (Tyr) residues. Phosphorylation of cytoplasmic Tyr renders these cell surface receptors competent to interact with proteins that link cell surface receptors to protein in the intracellular signaling pathways. Here we show that Tyr residues in the cytoplasmic domain of CD6 become phosphorylated upon T cell activation via the TCR complex. Tyr phosphorylation was observed when the T cells were activated by crosslinking CD3 or by cocrosslinking CD3 with CD2 or CD4, but not when the cells were stimulated by crosslinking CD2, CD4, or CD28 alone. Unlike other Tyr kinase substrates, such as the phospholipase C gamma 1-associated pp35/36 protein, whose level of Tyr phosphorylation is highest when T cells are activated by cocrosslinking CD3 with CD2, the levels of CD6 Tyr phosphorylation are highest when T cells were activated by cocrosslinking CD3 with CD4.
Blood Lead Levels and Serum Insulin-Like Growth Factor 1 Concentrations in Peripubertal Boys
Authors: Abby F. Fleisch, Jane S. Burns, Paige L. Williams, Mary M. Lee, Oleg Sergeyev, Susan A. Korrick, Russ Hauser
Journal: Environmental Health Perspectives (2013)

Childhood lead exposure has been associated with growth delay. However, the association between blood lead levels (BLLs) and insulin-like growth factor 1 (IGF-1) has not been characterized in a large cohort with low-level lead exposure.
The Ups and Downs of the Estrogen Receptor
Authors: V. Craig Jordan
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.10.008 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12506162 The Ups and Downs of the Estrogen Receptor V. Craig JordanxV. Craig JordanSearch for articles by this author Show More The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL https://doi.org/10.1200/JCO.2003.10.008 Full Text PDF Figures and Tables "The Ups and Downs of the Estrogen Receptor." Journal of Clinical Oncology, 21(1), pp. 3–4© 2003 by American Society of Clinical Oncology
The AMPK-related kinase SNARK regulates hepatitis C virus replication and pathogenesis through enhancement of TGF-β signaling
Authors: Kaku Goto, Wenyu Lin, Leiliang Zhang, Nikolaus Jilg, Run-Xuan Shao, Esperance A.K. Schaefer, Hong Zhao, Dahlene N. Fusco, Lee F. Peng, Naoya Kato, Raymond T. Chung
Journal: Journal of Hepatology (2013)
The<i>GPR54</i>Gene as a Regulator of Puberty
Authors: Stephanie B. Seminara, Sophie Messager, Emmanouella E. Chatzidaki, Rosemary R. Thresher, James S. Acierno, Jenna K. Shagoury, Yousef Bo-Abbas, Wendy Kuohung, Kristine M. Schwinof, Alan G. Hendrick, Dirk Zahn, John Dixon, Ursula B. Kaiser, Susan A. Slaugenhaupt, James F. Gusella, Stephen O'Rahilly, Mark B.L. Carlton, William F. Crowley, Samuel A.J.R. Aparicio, William H. Colledge
Journal: New England Journal of Medicine (2003)

Puberty, a complex biologic process involving sexual development, accelerated linear growth, and adrenal maturation, is initiated when gonadotropin-releasing hormone begins to be secreted by the hypothalamus. We conducted studies in humans and mice to identify the genetic factors that determine the onset of puberty.We used complementary genetic approaches in humans and in mice. A consanguineous family with members who lacked pubertal development (idiopathic hypogonadotropic hypogonadism) was examined for mutations in a candidate gene, GPR54, which encodes a G protein-coupled receptor. Functional differences between wild-type and mutant GPR54 were examined in vitro. In parallel, a Gpr54-deficient mouse model was created and phenotyped. Responsiveness to exogenous gonadotropin-releasing hormone was assessed in both the humans and the mice.Affected patients in the index pedigree were homozygous for an L148S mutation in GPR54, and an unrelated proband with idiopathic hypogonadotropic hypogonadism was determined to have two separate mutations, R331X and X399R. The in vitro transfection of COS-7 cells with mutant constructs demonstrated a significantly decreased accumulation of inositol phosphate. The patient carrying the compound heterozygous mutations (R331X and X399R) had attenuated secretion of endogenous gonadotropin-releasing hormone and a left-shifted dose-response curve for gonadotropin-releasing hormone as compared with six patients who had idiopathic hypogonadotropic hypogonadism without GPR54 mutations. The Gpr54-deficient mice had isolated hypogonadotropic hypogonadism (small testes in male mice and a delay in vaginal opening and an absence of follicular maturation in female mice), but they showed responsiveness to both exogenous gonadotropins and gonadotropin-releasing hormone and had normal levels of gonadotropin-releasing hormone in the hypothalamus.Mutations in GPR54, a G protein-coupled receptor gene, cause autosomal recessive idiopathic hypogonadotropic hypogonadism in humans and mice, suggesting that this receptor is essential for normal gonadotropin-releasing hormone physiology and for puberty.
Spermine Oxidation Induced by <b> <i>Helicobacter pylori</i> </b> Results in Apoptosis and DNA Damage
Authors: Hangxiu Xu, Rupesh Chaturvedi, Yulan Cheng, Francoise I. Bussiere, Mohammad Asim, Micheal D. Yao, Darryn Potosky, Stephen J. Meltzer, Juong G. Rhee, Sung S. Kim, Steven F. Moss, Amy Hacker, Yanlin Wang, Robert A. Casero, Keith T. Wilson
Journal: Cancer Research (2004)

Abstract Oxidative stress is linked to carcinogenesis due to its ability to damage DNA. The human gastric pathogen Helicobacter pylori exerts much of its pathogenicity by inducing apoptosis and DNA damage in host gastric epithelial cells. Polyamines are abundant in epithelial cells, and when oxidized by the inducible spermine oxidase SMO(PAOh1) H2O2 is generated. Here, we report that H. pylori up-regulates mRNA expression, promoter activity, and enzyme activity of SMO(PAOh1) in human gastric epithelial cells, resulting in DNA damage and apoptosis. H. pylori-induced H2O2 generation and apoptosis in these cells was equally attenuated by an inhibitor of SMO(PAOh1), by catalase, and by transient transfection with small interfering RNA targeting SMO(PAOh1). Conversely, SMO(PAOh1) overexpression induced apoptosis to the same levels as caused by H. pylori. Importantly, in H. pylori-infected tissues, there was increased expression of SMO(PAOh1) in both human and mouse gastritis. Laser capture microdissection of human gastric epithelial cells demonstrated expression of SMO(PAOh1) that was significantly attenuated by H. pylori eradication. These results identify a pathway for oxidative stress-induced epithelial cell apoptosis and DNA damage due to SMO(PAOh1) activation by H. pylori that may contribute to the pathogenesis of the infection and development of gastric cancer.
New Markers of Inflammation and Endothelial Cell Activation
Authors: Paul E. Szmitko, Chao-Hung Wang, Richard D. Weisel, John R. de Almeida, Todd J. Anderson, Subodh Verma
Journal: Circulation (2003)

2][3][4][5][6] The vascular endothelium, located at the interface of blood and tissue, is able to sense changes in hemodynamic forces and bloodborne signals and react by synthesizing and releasing vasoactive substances.Vascular homeostasis is maintained by a balance between endothelium-derived relaxing and contracting factors.With disruption of this balance, mediated by inflammatory and traditional cardiovascular risk factors, the vasculature becomes susceptible to atheroma formation.Inflammatory mediators appear to play a fundamental role in the initiation, progression, and eventual rupture of atherosclerotic plaques.As evidence accumulates linking inflammatory processes to atherogenesis, markers of inflammation and endothelial activation may become useful by providing additional information about a patient's risk of developing cardiovascular disease, as well as providing new targets for treatment. 7,8This review article is the first part of a twoarticle series examining emerging markers of inflammation and cardiovascular disease.Part 1 will provide a brief overview of the link between inflammation, endothelial dysfunction, and atherosclerosis and will begin highlighting emerging inflammatory mediators of endothelial cell (EC) activation, a discussion that will be continued in Part 2.
Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression
Authors: Xiang Cai, Angy J Kallarackal, Mark D Kvarta, Sasha Goluskin, Kaitlin Gaylor, Aileen M Bailey, Hey-Kyoung Lee, Richard L Huganir, Scott M Thompson
Journal: Nature Neuroscience (2013)
Effects of Free Immunoglobulin Light Chains on Viral Myocarditis
Authors: Akira Matsumori, Miho Shimada, Xiao Jie, Hirokazu Higuchi, Tom Groot Kormelink, Frank A. Redegeld
Journal: Circulation Research (2010)

Rationale : In recent work, we have demonstrated a crucial role of mast cells in the development of viral myocarditis. Viral infection could lead to increased synthesis of free immunoglobulin light chains (FLC) and our earlier work showed that FLC can trigger mast cell activation. Objective : We studied the possible involvement of FLC in the pathogenesis of viral myocarditis, and therapeutic effects of FLC using an animal model of viral myocarditis. Methods and Results : DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis (EMC) virus. Serum levels and concentrations in the heart of κ FLC on day 14 in mice inoculated with EMC virus were significantly increased compared with controls. Myocardial viral concentration was significantly inhibited, the area of myocardial lesions was smaller in mice treated with κ or λ FLC, and survival of mice given FLC significantly improved. In contrast, an FLC antagonist deteriorated myocarditis. κ and λ FLC chains inhibited EMC viral replication in human amnion cells in vitro. λ FLC significantly increased the gene expression of interleukin-10 in the heart which was previously shown to improve viral myocarditis when given exogenously. FLC also tended to increase the gene expressions of interferon-α and -γ in the heart mice. Conclusions : FLC have antiviral and antiinflammatory effects and improved viral myocarditis in mice. FLC may be promising agents for the treatment of viral myocarditis.
CHANGES IN PIGMENT EPITHELIUM CELLS AND IRIS PIGMENT CELLS OF RANA PIPIENS INDUCED BY CHANGES IN ENVIRONMENTAL CONDITIONS
Authors: Eduard Uhlenhuth
Journal: The Journal of Experimental Medicine (1916)

1. Retina pigment epithelium cells and iris pigment cells are placed in an identical medium. 2. The differentiation into two different parts, as well as the pigment strains of the migrating pigment epithelium cells, is lost. The normally highly specialized cuticular structures disappear. The cells begin to move and assume a spindle shape, thus losing their original hexagonal shape. 3. The migrating iris pigment cells begin to show a distribution of the pigment, similar to that exhibited by the migrating pigment epithelium cells. The cuticular structures of this cell type also disappear. These cells also assume the ability of free movement and become spindle-shaped. 4. By means of these changes both cell types not only become more similar to the ordinary culture cell type, but also in certain respects, more like each other, whereas before explantation they were very unlike. In order to accomplish this the pigment epithelium cells must change much more thoroughly than the iris pigment cells. 5. The changes, particularly those of the pigment epithelium cells, show a definite relation to the changes of external factors, as they are the expression of the transmission from dissimilar conditions existing on different sides of the cells into conditions which are uniform on all sides.
Cold virus spurs range of remedies
Authors: Chris Anne Raymond
Journal: JAMA (1986)

Radiation is just one of the latest strategies to outfox the tenacious common cold viruses. Recent surveys indicate that acute respiratory illnesses account for more than half of all acute disabling disease, with colds being the most common of such disorders (<i>National Health Survey</i>, US Dept of Health, Education, and Welfare publication No. 79-1560. 1979:3). Colds occur at the rate of 100 million disabling cases annually, causing about 250 million days of restricted activity, and 30 million days lost at work or school. Sales of over-the-counter cold remedies amount to more than $1 billion annually, and these remedies apparently are used to treat two to five colds per American each year. Schoolchildren contract as many as a dozen colds each year (Fox JP and Hall CE:<i>Viruses in Families</i>. Littleton, Mass, PSG Publishing, 1985; Murphy W:<i>Coping with the Common Cold</i>. Alexandria, Va, Time-Life Books, 1981). It is figures like
Diagnosis of Genito-Urinary Tract Cancer by Detection of Minichromosome Maintenance 5 Protein in Urine Sediments
Authors: K. Stoeber
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Because cystoscopy is invasive and expensive and urine cytology has low sensitivity, alternative methods for detecting bladder cancer are sought. Minichromosome maintenance (Mcm) proteins have been used as diagnostic markers for cervical cancer. We investigated whether one Mcm protein, Mcm5, can be used to detect urothelial cancer cells in urine sediments. Methods: We used two monoclonal antibodies against His-tagged human Mcm5 (amino acids 367–582) in an immunofluorometric assay to measure Mcm5 levels in cells in the urine of 353 patients who presented with hematuria or lower urinary tract symptoms or who were undergoing follow-up cystoscopy for urothelial neoplasia. Urine samples were also subjected to routine cytologic analysis. Patients underwent upper urinary tract imaging and cystoscopy within 12 hours of producing the urine sample. Data were analyzed by comparing areas under a nonparametric receiver operating characteristics (ROC) curve and by McNemar's test and Fisher's exact test. All statistical tests were two-sided. Results: At the assay cut point where the false-negative and false-positive rates were the same, the Mcm5 test detected primary and recurrent bladder cancers with 87% (95% confidence interval [CI] = 77% to 94%) sensitivity and 87% (95% CI = 83% to 91%) specificity. At the cut point where the specificities of urine cytology and the Mcm5 test were equal (97%, 95% CI = 95% to 99%), the Mcm5 test was statistically significantly (P<.001) more sensitive than urine cytology, 73% (95% CI = 61% to 83%) versus 48% (95% CI = 35% to 60%). At the lower detection limit of the Mcm5 test, sensitivity was highest, 92% (95% CI = 83% to 97%) and specificity was 78% (95% CI = 72% to 83%). Patients with prostate cancer had higher levels of Mcm5 in their urine sediments than did men without malignancy (P<.001). Conclusions: Elevated levels of Mcm5 in urine sediments are highly predictive of bladder cancer.
Questions About the Role of Palifermin in Fluorouracil-Based Therapy for Metastatic Colorectal Cancer
Authors: Ian E. Haines
Journal: Journal of Clinical Oncology (2007)

entitled “PaliferminReduces the Incidence of Oral Mucositis in Patients With MetastaticColorectal Cancer With Fluorouracil-Based Chemotherapy” raised anumber of questions that require a response.The title of the article and its conclusion imply that paliferminreduces the incidence of oral mucositis in all patients with metasticcolorectal cancer on ﬂuorouracil (FU)-based chemotherapy. Isn’tthis misleading? The study only showed the dose of palifermanused is better than nothing in patients receiving the very speciﬁcMayo regimen of FU and folinic acid. One of the reasons that theMayo regimen is outdated and now considered an inappropriatetreatment for patients with metastatic colorectal cancer is that ithas a very high incidence of oral mucositis, a very debilitatingadverse effect.