tbuckley/cabot-search huggingface dataset:
Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development?
Authors: N. P.Y. Lee
Journal: Human Reproduction Update (2004)

The seminiferous tubule of the mammalian testis is largely composed of Sertoli and germ cells, which coordinate with Leydig cells in the interstitium and perform two major physiological functions, namely spermatogenesis and steroidogenesis respectively. Each tubule is morphologically divided into (i) the seminiferous epithelium composing Sertoli and germ cells, and (ii) the basement membrane (a modified form of extracellular matrix); underneath this lies the collagen fibril network, the myoid cell layer, and the lymphatic vessel, which collectively constitute the tunica propia. In the seminiferous epithelium, of rodent testes each type A1 spermatogonium (diploid, 2n) differentiates into 256 elongated spermatids (haploid, 1n) during spermatogenesis. Additionally, developing germ cells must migrate progressively from the basal to the luminal edge of the adluminal compartment so that fully developed spermatids can be released into the lumen at spermiation. Without this timely event of cell movement, spermatogenesis cannot reach completion and infertility will result. Yet developing round elongating/elongated spermatids must remain attached to the epithelium via a specialized Sertoli–germ cell actin-based adherens junction (AJ) type known as ectoplasmic specialization (ES), which is crucial not only for cell attachment but also for spermatid movement and orientation in the epithelium. However, the biochemical composition and molecular architecture of the protein complexes that constitute the ES have only recently been studied. Furthermore, the signalling pathways that regulate ES dynamics are virtually unknown. This review highlights recent advances in these two areas of research. It is expected that, if adequately expanded, these studies should yield new insights into the development of novel contraceptives targeted to perturb ES function in the testis. The potential to specifically target the ES may also mean that contraceptive action could be achieved without perturbing the hypothalamic–pituitary–testicular axis.
Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis.
Authors: K Lenz, H Hortnagl, W Druml, G Grimm, A Laggner, B Schneeweisz, G Kleinberger
Journal: Gut (1989)

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8-ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p less than 0.01), urine volume (108 (29)%; p less than 0.05) and sodium excretion (168 (30)%; p less than 0.05). The hyperdynamic circulation of hepatic failure, as characterised by increased cardiac index and heart rate as well as decreased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p less than 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and renin-angiotensin-axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).
An amino acid polymorphism within the RGD binding domain of platelet membrane glycoprotein IIIa is responsible for the formation of the Pena/Penb alloantigen system.
Authors: R Wang, K Furihata, J G McFarland, K Friedman, R H Aster, P J Newman
Journal: Journal of Clinical Investigation (1992)

The human Pena/Penb alloantigen system represents a naturally occurring polymorphism of human platelet membrane glycoprotein (GP) IIIa, and has previously been implicated in the onset of two important clinical syndromes, neonatal alloimmune thrombocytopenic purpura and posttransfusion purpura. To investigate the molecular basis of the polymorphism underlying the Pen alloantigen system, we used the polymerase chain reaction to amplify platelet-derived GPIIIa mRNA transcripts. DNA sequence analysis of amplified GPIIIa cDNAs from nucleotides 161 to 1341 (encompassing amino acid residues 22-414) revealed a G526<==>A526 polymorphism that segregated precisely with Pen phenotype in twelve other individuals examined. This nucleotide substitution results in an Arg (CGA) to Gln (CAA) polymorphism at amino acid 143 of GPIIIa. Interestingly, this polymorphic residue is located within the putative RGD binding site (residues 109-171) of GPIIIa. Platelet aggregation patterns of a Penb/b individual, however, were nearly normal in response to all physiological agonists tested, indicating that this polymorphism does not grossly affect integrin function. Short synthetic peptides encompassing residue 143 were unable to mimic either the Pena or Penb antigenic determinants, suggesting that the Pen epitopes are dependent upon proper folding of the polypeptide chain. Finally, we constructed allele-specific recombinant forms of GPIIIa that differed only at amino acid residues 143. Whereas anti-Pena alloantibodies were able to recognize the Arg143 recombinant form of GPIIIa, anti-Penb antibodies were not. Conversely, anti-Penb alloantibodies were reactive only with the Gln143 isoform of the GPIIIa molecule. It thus appears that amino acid 143 of GPIIIa is not only associated with Pen phenotype, but specifically controls the formation and expression of the Pen alloantigenic determinants.
MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis
Authors: Ivan O Rosas, Thomas J Richards, Kazuhisa Konishi, Yingze Zhang, Kevin Gibson, Anna E Lokshin, Kathleen O Lindell, Jose Cisneros, Sandra D MacDonald, Annie Pardo, Frank Sciurba, James Dauber, Moises Selman, Bernadette R Gochuico, Naftali Kaminski
Journal: PLoS Medicine (2008)

Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression. Methods and Findings We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins—MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A—that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%–100%) and specificity of 98.1% (95% CI 89.9%–100%). Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%–100%) and specificity of 87.2% (95% CI 72.6%–95.7%). We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD), as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC%) and percent predicted carbon monoxide diffusing capacity (DLCO%). Conclusions Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung microenvironment and distinguish IPF from other chronic lung diseases. Additionally, increased MMP7 concentration may be indicative of asymptomatic ILD and reflect disease progression.
BLOOD PRESSURE, BUN, CREATININE, CONGESTIVE HEART FAILURE AND CARDIAC ARREST (B2C3 SCORE) PREDICTS PROCEDURE MORTALITY FOR ELECTIVE ICD IMPLANTATION: DATA FROM THE NATIONAL ICD REGISTRY (ICDR®)
Authors: David E. Haines, Jeptha P. Curtis, Yongfei Wang
Journal: Journal of the American College of Cardiology (2010)
The evolution and psychology of self-deception
Authors: William von Hippel, Robert Trivers
Journal: Behavioral and Brain Sciences (2011)

In this article we argue that self-deception evolved to facilitate interpersonal deception by allowing people to avoid the cues to conscious deception that might reveal deceptive intent. Self-deception has two additional advantages: It eliminates the costly cognitive load that is typically associated with deceiving, and it can minimize retribution if the deception is discovered. Beyond its role in specific acts of deception, self-deceptive self-enhancement also allows people to display more confidence than is warranted, which has a host of social advantages. The question then arises of how the self can be both deceiver and deceived. We propose that this is achieved through dissociations of mental processes, including conscious versus unconscious memories, conscious versus unconscious attitudes, and automatic versus controlled processes. Given the variety of methods for deceiving others, it should come as no surprise that self-deception manifests itself in a number of different psychological processes, and we discuss various types of self-deception. We then discuss the interpersonal versus intrapersonal nature of self-deception before considering the levels of consciousness at which the self can be deceived. Finally, we contrast our evolutionary approach to self-deception with current theories and debates in psychology and consider some of the costs associated with self-deception.
The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in <i>msh2</i>−/− <i>ung</i>−/− mice
Authors: Kanmin Xue, Cristina Rada, Michael S. Neuberger
Journal: The Journal of Experimental Medicine (2006)

Immunoglobulin (Ig) class switching is initiated by deamination of C-->U within the immunoglobulin heavy chain locus, catalyzed by activation-induced deaminase (AID). In the absence of uracil-DNA glycosylase (UNG) and the homologue of bacterial MutS (MSH)-2 mismatch recognition protein, the resultant U:G lesions are not processed into switching events but are fixed by replication allowing sites of AID-catalyzed deamination to be identified by the resulting C-->T mutations. We find that AID targets cytosines in both donor and acceptor switch regions (S regions) with the deamination domains initiating approximately 150 nucleotides 3' of the I exon start sites and extending over several kilobases (the IgH intronic enhancer is spared). Culturing B cells with interleukin 4 or interferon gamma specifically enhanced deamination around Sgamma1 and Sgamma2a, respectively. Mutation spectra suggest that, in the absence of UNG and MSH2, AID may occasionally act at the mu switch region in an apparently processive manner, but there is no marked preference for targeting of the transcribed versus nontranscribed strand (even in areas capable of R loop formation). The data are consistent with switch recombination being triggered by transcription-associated, strand-symmetric AID-mediated deamination at both donor and acceptor S regions with cytokines directing isotype specificity by potentiating AID recruitment to the relevant acceptor S region.
The Case for “Outsourcing” Diabetes Care
Authors: Mayer B. Davidson
Journal: Diabetes Care (2003)

Diabetes has a profound effect on the health of our population as well as on our economy. Diabetic retinopathy is the leading cause of blindness in people between 20 and 74 years of age (1). Diabetic nephropathy is the leading cause of patients undergoing dialysis for end-stage renal disease (2). Diabetic peripheral neuropathy is the underlying cause of nontraumatic lower-extremity amputations in diabetic patients (3). More than half of lower-extremity amputations occur in people with diabetes (4) who at that time constituted only 4.5% of the population (5). The prevalence of coronary artery disease is twofold higher in men with diabetes and fourfold higher in women with diabetes compared with appropriate nondiabetic control subjects (6). Strokes are two to three times more common in people with diabetes than in those without the disease (7). Peripheral vascular disease is also much more common in diabetic patients compared with nondiabetic individuals (8).

The total cost of caring for people with diabetes in this country in 1992 (106 billion dollars) represented 15% of the total health care budget (720 billion dollars) (5). In a more recent study, the American Diabetes Association (ADA) study found that in 1997 the specific (direct) costs for diabetes care was 44 billion dollars with another 54 billion dollars lost to the economy through indirect costs (i.e., short- and long-term disability and losses secondary to premature mortality) (9). Medicare spent 26.5% of its budget on diabetic patients (5). The excess costs for diabetes in Kaiser-Permanente in Northern California amounted to $3,494 per patient per year (10). Much of these increased costs for diabetes were for related complications. There were progressively increasing costs associated with worsening diabetic control in patients with either diabetes alone or with hypertension and heart disease (11). Increased glycated hemoglobin levels predicted higher rates of …
Direct evidence for cytotoxicity associated with expression of hepatitis delta virus antigen
Authors: Susan M. Cole, Eric J. Gowans, Thomas B. Macnaughton, Pauline De La M. Hall, Christopher J. Burrell
Journal: Hepatology (1991)

It has been postulated that hepatocyte injury resulting from infection with hepatitis D virus may be caused by a direct virus cytotoxicity in contrast to immune-mediated injury associated with hepatitis B virus. We have transfected HeLa and HepG2 continuous cell lines with a recombinant plasmid containing the hepatitis D antigen gene under the inducible control of the human metallothionein promoter. The addition of zinc to the cell culture medium then led to the expression of hepatitis D antigen associated with, in the short term, a significant reduction in the rate of RNA but not DNA synthesis and, in the longer term, cell death. The necrotic cells had pyknotic nuclei and shrunken eosinophilic cytoplasm; these necrotic cells resembled the apoptotic bodies seen in hepatitis D virus-related hepatitis. The level of hepatitis D antigen in individual cells that produced these changes was similar to the level of hepatitis D antigen in hepatocytes from a chimpanzee with acute hepatitis D virus infection. We conclude that the expression of hepatitis D antigen resulted in significant cytotoxic changes in these cells, providing strong support for the view that hepatitis D antigen may be specifically cytotoxic to infected hepatocytes in vivo.
Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo
Authors: Thierry VandenDriessche, Lieven Thorrez, Luigi Naldini, Antonia Follenzi, Lieve Moons, Zwi Berneman, Desire Collen, Marinee K. L. Chuah
Journal: Blood (2002)
Arrhythmic Mitral Valve Prolapse and Sudden Cardiac Death
Authors: Cristina Basso, Martina Perazzolo Marra, Stefania Rizzo, Manuel De Lazzari, Benedetta Giorgi, Alberto Cipriani, Anna Chiara Frigo, Ilaria Rigato, Federico Migliore, Kalliopi Pilichou, Emanuele Bertaglia, Luisa Cacciavillani, Barbara Bauce, Domenico Corrado, Gaetano Thiene, Sabino Iliceto
Journal: Circulation (2015)

Background— Mitral valve prolapse (MVP) may present with ventricular arrhythmias and sudden cardiac death (SCD) even in the absence of hemodynamic impairment. The structural basis of ventricular electric instability remains elusive. Methods and Results— The cardiac pathology registry of 650 young adults (≤40 years of age) with SCD was reviewed, and cases with MVP as the only cause of SCD were re-examined. Forty-three patients with MVP (26 females; age range, 19–40 years; median, 32 years) were identified (7% of all SCD, 13% of women). Among 12 cases with available ECG, 10 (83%) had inverted T waves on inferior leads, and all had right bundle-branch block ventricular arrhythmias. A bileaflet involvement was found in 70%. Left ventricular fibrosis was detected at histology at the level of papillary muscles in all patients, and inferobasal wall in 88%. Living patients with MVP with (n=30) and without (control subjects; n=14) complex ventricular arrhythmias underwent a study protocol including contrast-enhanced cardiac magnetic resonance. Patients with either right bundle-branch block type or polymorphic complex ventricular arrhythmias (22 females; age range, 28–43 years; median, 41 years), showed a bileaflet involvement in 70% of cases. Left ventricular late enhancement was identified by contrast-enhanced cardiac magnetic resonance in 93% of patients versus 14% of control subjects ( P &lt;0.001), with a regional distribution overlapping the histopathology findings in SCD cases. Conclusions— MVP is an underestimated cause of arrhythmic SCD, mostly in young adult women. Fibrosis of the papillary muscles and inferobasal left ventricular wall, suggesting a myocardial stretch by the prolapsing leaflet, is the structural hallmark and correlates with ventricular arrhythmias origin. Contrast-enhanced cardiac magnetic resonance may help to identify in vivo this concealed substrate for risk stratification.
Autoantibody to an Immunoregulatory Inducer Population in Patients with Juvenile Rheumatoid Arthritis
Authors: Chikao Morimoto, Ellis L. Reinherz, Yves Borel, Evangelia Mantzouranis, Alfred D. Steinberg, Stuart F. Schlossman
Journal: Journal of Clinical Investigation (1981)

The human inducer (T4(+)) and reciprocal cytotoxic/suppressor (T5(+)/T8(+)) subsets have been defined by monoclonal antibodies. In the present study, we examined the relationship of naturally occurring anti-T cell autoantibodies found in patients with active juvenile rheumatoid arthritis (JRA) to these subsets. In one approach, normal T cells were treated with anti-T4 or anti-T8 to eliminate the corresponding subset of cells and then analyzed for reactivity with JRA sera. It was found that JRA sera were reactive with only 15% of an enriched cytotoxic/suppressor population, whereas they reacted with 37% of an enriched inducer population. In reciprocal studies, JRA(+) T cells were eliminated with JRA sera and complement and the residual T cells (JRA(-)) reacted with monoclonal antibodies and indirect immunofluorescence on a fluorescence-activated cell sorter. As expected, the JRA sera and complement treatment of unfractionated T cells markedly diminished the T4(+) subset, whereas there was a concomitant increase in T cells reactive with anti-T5 and anti-T8. A similar diminution in T4(+) T cells was found in the circulating peripheral T cell compartment of patients with active JRA who possessed the JRA antibody. Functional studies demonstrated that removal of the JRA(+) population of T cells diminished phytohemagglutinin and soluble antigen proliferative responses, both of which were previously shown to be functions of T4(+) T cells. More importantly, in the absence of JRA(+) T cells, pokeweed mitogen-stimulated immunoglobulin production was markedly enhanced, despite the concomitant increase in T5(+)/T8(+) cytotoxic/suppressor cells. These results suggest that the JRA serum may define a Qal-like antigen found predominantly on the human inducer population which could activate suppressor and/or other feedback regulatory cells.
Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis
Authors: Brad E. Morrison, Stacy J. Park, Jill M. Mooney, Borna Mehrad
Journal: Journal of Clinical Investigation (2003)

Invasive aspergillosis is a severe pneumonia that is usually fatal despite currently available therapy. The disease disproportionately afflicts immunocompromised patients, indicating the critical importance of the immune status of the host in this infection, but the defense mechanisms against this pathogen remain incompletely understood. In the current study, we hypothesized that the chemokine ligand monocyte chemotactic protein-1, also designated CC chemokine ligand-2 (MCP-1/CCL2) is necessary for effective host defense against invasive aspergillosis in immunocompromised hosts. We found a rapid and marked induction of MCP-1/CCL2 in the lungs of neutropenic mice with invasive aspergillosis. Neutralizing MCP-1/CCL2 resulted in twofold greater mortality and greater than threefold increase in pathogen burden in the lungs. Neutralization of MCP-1/CCL2 also resulted in reduced recruitment of NK cells to the lungs at early time points, but did not affect the number of other leukocyte effector cells in the lungs. Ab-mediated depletion of NK cells similarly resulted in impaired defenses against the infection, resulting in a greater than twofold increase in mortality and impaired clearance of the pathogen from the lungs. These data establish MCP-1/CCL2–mediated recruitment of NK cells to the lungs as a critical early host defense mechanism in invasive aspergillosis and demonstrate NK cells to be an important and previously unrecognized effector cell in this infection.
Diagnosing lung cancer earlier in the UK
Authors: M. Weir, W. J. A. Anderson, E. Murtagh, R. Donnelly, J. Leggett, J. Wieboldt
Journal: Thorax (2010)

We read with interest the article by Hubbard et al who raise late diagnosis as a key determinant of poor lung cancer survival in the UK.1 We would like to highlight discrepancies in rates of radical treatment use as another contributory factor. Figures from the Eurocare 4 study2 suggest 5-year survival figures in Northern Ireland have been higher than in England and Wales or Scotland (table 1).2–4 This could reflect differences in patient demographics, disease, method of recording or treatment modality. …
Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial
Authors: S Yusuf, K Teo, C Anderson, J Pogue, L Dyal, I Copland, H Schumacher, G Dagenais, P Sleight
Journal: The Lancet (2008)