tbuckley/cabot-search huggingface dataset:
Gene Transfer of Heterologous G Protein–Coupled Receptors to Cardiomyocytes
Authors: Karl-Ludwig Laugwitz, Hans-Jörg Weig, Alessandra Moretti, Eva Hoffmann, Peter Ueblacker, Ingo Pragst, Kai Rosport, Albert Schömig, Martin Ungerer
Journal: Circulation Research (2001)

Abstract —In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to β-adrenergic stimulation. Parathyroid hormone (PTH)–related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective β-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V 2 vasopressin receptors (rV 2 -Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant β 2 -adrenergic receptors (rβ 2 -ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V 2 -Rs are uniquely coupled to Gs, PTH1-Rs and β 2 -ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rβ 2 -ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV 2 -R–expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of β 2 -ARs. In the absence of receptor agonists, rPTH1-Rs and rβ 2 -ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV 2 -Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V 2 -Rs might be more suited to test the effects of cAMP-stimulating receptors in heart failure than that of PTH1-Rs or β 2 -ARs.
Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression
Authors: Ralf C. Bargou, Karsten Jürchott, Christian Wagener, Stephan Bergmann, Sylvia Metzner, Kurt Bommert, Markus Y. Mapara, Klaus-Jürgen Winzer, Manfred Dietel, Bernd Dörken, Hans-Dieter Royer
Journal: Nature Medicine (1997)
Peroxisome proliferator activated receptor-γ modulates reactive oxygen species generation and activation of nuclear factor-κB and hypoxia-inducible factor 1α in allergic airway disease of mice
Authors: Kyung Sun Lee, So Ri Kim, Seoung Ju Park, Hee Sun Park, Kyung Hoon Min, Sun Mi Jin, Moon Kyu Lee, Uh Hyun Kim, Yong Chul Lee
Journal: Journal of Allergy and Clinical Immunology (2006)
Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity
Authors: Anthony J. Slavin, Jeanne M. Soos, Olaf Stuve, Juan C. Patarroyo, Howard L. Weiner, Adriano Fontana, Elizabeth K. Bikoff, Scott S. Zamvil
Journal: Journal of Clinical Investigation (2001)

The role of processing in antigen (Ag) presentation and T cell activation in experimental allergic encephalomyelitis (EAE) was evaluated in wild-type mice, mice that selectively express either Ii p31 or p41, and mice completely deficient in Ii or H-2M. We demonstrate that processing of myelin oligodendrocyte glycoprotein (MOG) is required for presentation of the dominant encephalitogenic MOG epitope, p35-55. Ii p31- and p41-expressing mice developed EAE with similar incidence to wild-type mice, although p41 mice had a more severe course. Ag-presenting cells (APCs) from Ii- or H-2M–deficient mice could present p35-55, but not MOG, demonstrating that these APCs could not process native MOG. Ii- and H-2M–deficient mice were not susceptible to EAE by immunization with p35-55 or MOG or by adoptive transfer of encephalitogenic T cells. However, CD4+ T cells from p35-55–immunized H-2M–deficient mice proliferated, secreted IFN-γ, and transferred EAE to wild-type, but not H-2M–deficient, mice. Thus, EAE resistance in H-2M–deficient mice is not due to an inability of APCs to present p35-55, or an intrinsic defect in the encephalitogenic T cell repertoire, but reflects a defect in APC function. Our results indicate that processing is required for initial Ag presentation and CNS T cell activation and suggest that autopathogenic peptides of CNS autoantigen may not be readily available for presentation without processing.
Book Review Small for Gestational Age: Causes and Consequences (Pediatric and Adolescent Medicine. Vol. 13.) Edited by Wieland Kiess, Steven D. Chernausek, and Anita C.S. Hokken-Koelega. 167 pp., illustrated. Basel, Switzerland, Karger, 2009. $158. 978-3-8055-8657-3 (cloth); 978-3-8055-8658-0 (e-book).
Authors: Eric C. Eichenwald
Journal: New England Journal of Medicine (2009)
A multicenter trial of intravenous APSAC versus rtPA in acute myocadial infarction. Assessment of efficacy and safety
Authors: J.P. Bassand, J. Cassagnes, J. Machecourt, T. Anguenot, J.R. Lusson, B. Bernard, A. Vuillemenot, J.E. Wolf, D. Vacher
Journal: Journal of the American College of Cardiology (1990)
Anicteric Hepatitis Associated With Australia Antigen
Authors: Alton I. Sutnick
Journal: JAMA (1968)

The frequency of Australia antigen is high in patients with Down's syndrome in large institutions (27.7%) and is low in patients without this syndrome in the same institutions (3.2%). It is rare in patients with Down's syndrome in small institutions (1.5%) and absent in newborn patients and those who are not institutionalized. Serum glutamic pyruvic transaminase levels were studied in age- and sex-matched groups of 16 patients with Down's syndrome and Australia antigen [phenotype Au (1)], 16 with Down's syndrome but without Australia antigen [Au(0)] and 16 Au(0) mental defectives without Down's syndrome. The findings indicated active liver cell breakdown in Au(1) patients, and were confirmed in an extensive study including 581 individuals. The findings are best explained by the operation of an environmental factor, probably infectious, present in the large institutions, and a host susceptibility factor present in association with Down's syndrome.
Persistent Asymptomatic Isolated Microscopic Hematuria in Israeli Adolescents and Young Adults and Risk for End-Stage Renal Disease
Authors: Asaf Vivante
Journal: JAMA (2011)

Few data are available on long-term outcomes among adolescents and young adults with persistent asymptomatic isolated microscopic hematuria.To evaluate the risk of end-stage renal disease (ESRD) in adolescents and young adults with persistent asymptomatic isolated microscopic hematuria.Nationwide, population-based, retrospective cohort study using medical data from 1,203,626 persons aged 16 through 25 years (60% male) examined for fitness for military service between 1975 and 1997 were linked to the Israeli treated ESRD registry. Incident cases of treated ESRD from January 1, 1980, to May 31, 2010, were included. Cox proportional hazards models were used to estimate the hazard ratio (HR) of treated ESRD among those diagnosed as having persistent asymptomatic isolated microscopic hematuria.Treated ESRD onset, defined as the date of initiation of dialysis treatment or the date of renal transplantation, whichever came first.Persistent asymptomatic isolated microscopic hematuria was diagnosed in 3690 of 1,203,626 eligible individuals (0.3%). During 21.88 (SD, 6.74) years of follow-up, treated ESRD developed in 26 individuals (0.70%) with and 539 (0.045%) without persistent asymptomatic isolated microscopic hematuria, yielding incidence rates of 34.0 and 2.05 per 100,000 person-years, respectively, and a crude HR of 19.5 (95% confidence interval [CI], 13.1-28.9). A multivariate model adjusted for age, sex, paternal country of origin, year of enrollment, body mass index, and blood pressure at baseline did not substantially alter the risk associated with persistent asymptomatic isolated microscopic hematuria (HR, 18.5 [95% CI, 12.4-27.6]). A substantially increased risk for treated ESRD attributed to primary glomerular disease was found for individuals with persistent asymptomatic isolated microscopic hematuria compared with those without the condition (incidence rates, 19.6 vs 0.55 per 100,000 person-years, respectively; HR, 32.4 [95% CI, 18.9-55.7]). The fraction of treated ESRD attributed to microscopic hematuria was 4.3% (95% CI, 2.9%-6.4%).Presence of persistent asymptomatic isolated microscopic hematuria in persons aged 16 through 25 years was associated with significantly increased risk of treated ESRD for a period of 22 years, although the incidence and absolute risk remain quite low.
Relationships among islet cell antibodies, residual β-cell function, and metabolic control in patients with insulin-dependent diabetes mellitus of long duration: Use of a sensitive C-peptide radioimmunoassay
Authors: Koji Nakanishi, Tetsuro Kobayashi, Hikari Miyashita, Minoru Ohkubo, Tadao Sugimoto, Toshio Murase, Kinori Kosaka, Ken Inouye, Masao Kono
Journal: Metabolism (1990)
Analysis of MHC Encoded Antigen-processing Genes TAP1 and TAP2 Polymorphisms in Sarcoidosis
Authors: PATRICK J. FOLEY, PENELOPE A. LYMPANY, ELZBIETA PUSCINSKA, JAN ZIELINSKI, KENNETH I. WELSH, ROLAND M. du BOIS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Sarcoidosis is a chronic granulomatous disease of unknown etiology. Several studies have suggested involvement of human leukocyte antigen (HLA) genes in sarcoidosis susceptibility. HLA associations described have not been consistent, possibly because of additional susceptibility genes adjacent to or within the major histocompatibility complex (MHC) such as genes for the transporter associated with antigen processing (TAP). The aim of this study was to analyze TAP gene polymorphisms in patients with sarcoidosis using the amplificatory refraction mutation system (ARMS) PCR. To determine whether any association between TAP gene variation and sarcoidosis was ethnic-independent we examined two European populations: 117 unrelated UK Caucasoid patients with sarcoidosis and 290 healthy UK control subjects, and 87 unrelated Polish Slavonic patients with sarcoidosis and 158 healthy Polish control subjects. We detected significant differences in TAP2 between the UK control and patient groups, and in TAP2 between the Polish control and patient groups. Comparing the UK and Polish control groups, we observed a difference in TAP1. Examination of HLA-DPB1 in our UK population showed no associations with disease or between variants at the TAP gene loci and HLA-DPB1 variants. These results suggest associations at the TAP loci occur independently of HLA-DPB1 associations, that TAP associations seen may be involved in determining sarcoidosis susceptibility, and that such susceptibilities differ between UK and Polish populations. This first study of TAP genes in UK and Polish sarcoid populations has demonstrated the importance of using multiple defined ethnic populations in defining the role genetic factors play in sarcoidosis susceptibility and the importance of candidate gene studies.
Sertraline approved for post-traumatic stress disorder
Authors: S. Gottlieb
Journal: BMJ (1999)

<h3>Abstract</h3> Marine sediments harbor a vast amount of Earth’s microbial biomass, yet little is understood regarding how cells subsist in this low-energy, presumably slow-growth environment. Cells in marine sediments may require additional methods for genetic regulation, such as epigenetic modification via DNA methylation. We investigated this potential phenomenon within a shallow estuary sediment core spanning 100 years of age across its depth. Here we provide evidence of dynamic community m5-cytosine methylation within estuarine sediment metagenomes using a methylation-sensitive Illumina assay. The methylation states of individual CpG sites were reconstructed and quantified across three depths within the sediment core. A total of 6254 CpG sites were aligned for direct comparison of methylation states between samples, with 4235 sites mapped to taxa and genes. Our results demonstrate the presence of differential methylation within environmental CpG sites across an age/depth gradient of sediment. We show that epigenetic modification can be detected within complex environmental communities. The change in methylation state of environmentally relevant genes across depths may indicate a dynamic role of DNA methylation in biogeochemical processes.
CSF-1 signals directly to renal tubular epithelial cells to mediate repair in mice
Authors: Julia Menke, Yasunori Iwata, Whitney A. Rabacal, Ranu Basu, Yee G. Yeung, Benjamin D. Humphreys, Takashi Wada, Andreas Schwarting, E. Richard Stanley, Vicki R. Kelley
Journal: Journal of Clinical Investigation (2009)

Tubular damage following ischemic renal injury is often reversible, and tubular epithelial cell (TEC) proliferation is a hallmark of tubular repair. Macrophages have been implicated in tissue repair, and CSF-1, the principal macrophage growth factor, is expressed by TECs. We therefore tested the hypothesis that CSF-1 is central to tubular repair using an acute renal injury and repair model, ischemia/reperfusion (I/R). Mice injected with CSF-1 following I/R exhibited hastened healing, as evidenced by decreased tubular pathology, reduced fibrosis, and improved renal function. Notably, CSF-1 treatment increased TEC proliferation and reduced TEC apoptosis. Moreover, administration of a CSF-1 receptor-specific (CSF-1R-specific) antibody after I/R increased tubular pathology and fibrosis, suppressed TEC proliferation, and heightened TEC apoptosis. To determine the contribution of macrophages to CSF-1-dependent renal repair, we assessed the effect of CSF-1 on I/R in mice in which CD11b+ cells were genetically ablated and determined that macrophages only partially accounted for CSF-1-dependent tubular repair. We found that TECs expressed the CSF-1R and that this receptor was upregulated and coexpressed with CSF-1 in TECs following renal injury in mice and humans. Furthermore, signaling via the CSF-1R stimulated proliferation and reduced apoptosis in human and mouse TECs. Taken together, these data suggest that CSF-1 mediates renal repair by both a macrophage-dependent mechanism and direct autocrine/paracrine action on TECs.
<i>Die Progressive Myoklonus-Epilepsie (Unverricht's Myokionie)</i>. Von Dr. Herman Lundborg, privatdozent der psychiatric und neurologie in Upsala. (Herausgegeben mit untersfutzung aus Wilhelm Ekman's Universitatsfonds.) Progressive Myoclonus-Epilepsy
Authors: L. Pierce Clark
Journal: American Journal of Psychiatry (1904)
A rehabilitation ward in a district general hospital: first three years' experience.
Authors: K. J. Walsh, M. P. Barnes, D. L. McLellan
Journal: BMJ (1988)

The experience of the first three years9 work on a ward for the rehabilitation of patients was reviewed. Adults with physical disabilities or mixed physical and psychological disabilities, including unstable or deteriorating conditions, were accepted for intensive rehabilitation. Most patients had neurological disorders. The ward policy was that each patient had considerable time with the therapist, maximum personal independence was encouraged, and multidisciplinary staff meetings were held to agree the goals of treatment. Much effort was spent helping patients and relatives to adapt to conditions of progressive disability, but the response to questionnaires suggested that these patients as well as those who did improve received some benefit from being on the ward. Overall the benefits of the intensive rehabilitation that was offered on this ward outweighed those from short stays on medical wards.
The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic nephritis in rats.
Authors: S M Mauer, A J Fish, N K Day, A F Michael
Journal: Journal of Clinical Investigation (1974)

These studies were designed to explore the effects of nephrotoxic serum (NTS) in rats on the uptake and processing by the glomerular mesangium of intravenously administered protein macromolecules (radiolabeled aggregated human IgG, [125I]AHIgG). Measurements of [125I]AHIgG levels in preparations of isolated glomeruli correlated well with qualitative estimates of glomerular IgG deposition seen by immunofluorescent microscopy. Rats given 2 ml NTS received 25 mg/100 g body wt [125I]AHIgG 48 h later and were sacrificed at varying time intervals thereafter. NTS-treated animals demonstrated a marked increase in glomerular uptake of [125I]AHIgG as compared with concurrent controls but a normal ability to clear [125I]AHIgG from the mesangium over 72 hr. Animals given 1.0, 0.5, and 0.25 ml NTS had neither proteinuria nor significant light microscopic changes, yet had increased uptake of [125I]AHIgG of 4.4, 3.0, and 2.1 times control values, respectively at 8 h after the infusion of aggregates. Rats given 1 ml NTS and 12.5, 6.25, and 3.125 mg [125I]AHIgG/100 g body wt had increased glomerular uptake at 8 h, but there was, within both NTS and control groups, a disproportionate decrease in uptake at lower [125I]AHIgG doses. Rats given cobra venom factor (CoF) followed by a NTS shown to be complement dependent (proteinuria reduced by prior complement depletion with CoF) had less mesangial [125I]AHIgG uptake than NTS controls but greater uptake compared with normal controls. CoF itself had no effect on mesangial or reticuloendothelial system [125I]AHIgG uptake. These studies demonstrate a striking change in glomerular mesangial activity after fixation of nephrotoxic antibodies to the glomerular basement membrane, even in the absence of proteinuria and suggest that subtle alterations of the filtration surface can influence mesangial function. The effect of NTS on the mesangium is due, in large part, to the glomerular injury and proteinuria which nephrotoxic antibodies produce.
International Assessment of the Quality of Clinical Practice Guidelines in Oncology Using the Appraisal of Guidelines and Research and Evaluation Instrument
Authors: J.S. Burgers, B. Fervers, M. Haugh, M. Brouwers, G. Browman, T. Philip, F.A. Cluzeau
Journal: Journal of Clinical Oncology (2004)

Purpose To describe the quality of oncology guidelines developed in different countries. Methods The Appraisal of Guidelines and Research and Evaluation (AGREE) Instrument was used to assess the quality of 100 guidelines (including 32 oncology guidelines) from 13 countries. The criteria of the instrument are grouped into six quality domains: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence. Results Oncology guidelines had significantly higher scores on rigor of development than nononcology guidelines (42.2% v 29.4%; P = .02). In particular, systematic methods to search for evidence were more often used (P = .01); the methods for formulating the recommendations were more clearly described (P = .02); and health benefits, risks, and side effects were more often considered in formulating the recommendations (P = .03). Although the standardized scores for the other domains were not significantly different, the oncology guidelines had significantly higher scores for items measuring inclusion of all relevant professional groups (P = .05), consideration of patient views (P = .04), and presentation of different options (P = .05). Only three organizations producing oncology guidelines had standardized scores more than 60% for more than three domains. Conclusion The quality of clinical practice guidelines (CPGs) is modest in general, but for certain domains, oncology guidelines seem to be of better quality than others. The experience of the organization may explain higher scores for some items. Research projects and training aimed at improving the quality of guidelines should be developed. The AGREE instrument could provide a basis for defining steps in a shared development approach to produce high-quality CPGs.
ACETYLSALICYLIC ACID DEATHS
Authors: E. M. Cunningham
Journal: JAMA (1941)

<h3>To the Editor:—</h3> I note inThe Journalof January 11, page 145, the article about deaths from acetylsalicylic acid. In the village of Vandalia, Mich., 5 miles from Cassopolis, is a man who has been a chronic invalid suffering from arthritis deformans for more than twenty years. For seventeen years he has been confined to the use of a wheel chair. The records indicate, and the facts are supported by members of his family, that he has been taking 125 grains (8 Gm.) of aspirin daily for seventeen years without any apparent harmful effects. His family say that they have been unable to reduce the amount.
An Electrocautery Pleural Biopsy for the Diagnosis of Desmoplastic Malignant Mesothelioma During Semirigid Thoracoscopy
Authors: Shinji Sasada, Kunimitsu Kawahara, Teruo Iwasaki, Tomonori Hirashima, Teruomi Miyazawa
Journal: Journal of Thoracic Oncology (2008)
Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency.
Authors: J Weber, J M Werre, H W Julius, J J Marx
Journal: Annals of the Rheumatic Diseases (1988)

Mucosal uptake, mucosal transfer, and retention of a physiological dose of ferrous iron were studied in women with active rheumatoid arthritis (RA): 19 with normal and 17 with depleted bone marrow iron stores. Control subjects were 26 normal women and 20 women with uncomplicated iron deficiency. Iron absorption was measured with 59Fe as a tracer and by whole body counting. Compared with controls, final iron retention was considerably decreased in both groups of patients with RA. Analysis of the two sequential steps of iron absorption showed that mucosal uptake was normal in iron replete patients with RA but was significantly lower in patients with RA with depleted iron stores compared with iron deficient controls. Mucosal transfer of iron was considerably decreased in patients with RA with normal iron stores. The impaired absorption of iron in patients with active RA may delay the correction of the haemoglobin concentration when anaemia of chronic disease is complicated by iron deficiency.
STRUCTURE AND DEVELOPMENT OF VIRUSES OBSERVED IN THE ELECTRON MICROSCOPE
Authors: Councilman Morgan, Solon A. Ellison, Harry M. Rose, Dan H. Moore
Journal: The Journal of Experimental Medicine (1954)

Vaccinia and fowl pox viruses were visualized by the electron microscope in sections of infected chorioallantoic membrane of chicken embryos. The viruses were of similar structure and size, averaging 200 x 300 mmicro with considerable individual variation. Intracytoplasmic viral particles contained a dense, nucleus-like body (nucleoid) separated from granular material (viroplasm) by a zone of lesser density. They were enclosed by a single membrane. Near the surface of the host cell and in the extracellular space the particles consisted of a central body of variable shape and density enclosed by a double membrane. The initial sites of development were confined to the cytoplasm of the host cell. Before release from the host cell the viral nucleoids appeared to enlarge and to occupy a central position within the particle, which became enclosed by a double limiting membrane. The brick-shaped forms found after removal of the embedding plastic from thick sections indicated that drying caused characteristic distortion of certain viral particles.