tbuckley/cabot-search huggingface dataset:
Uptake of low density lipoproteins by rat tissues. Special emphasis on the luteinized ovary.
Authors: E Reaven, Y D Chen, M Spicher, S F Hwang, C E Mondon, S Azhar
Journal: Journal of Clinical Investigation (1986)

The aim of this study was to determine how luteal cells of the hormone-primed (luteinized) ovary process low density lipoproteins (LDL). Ovary uptake of perfused 125I-LDL was assessed by tissue levels of radioactivity; the distribution of LDL protein in cells was assessed on autoradiograms of the fixed tissue; and the level of stimulation of steroidogenesis, as well as degradation of LDL protein, was assessed on effluent perfusion samples. Human LDL ligand used in these studies was rigorously defined biochemically and physiologically. Homologous (rat) LDL was used as a special ligand control. Other tissue controls included the use of perfused or in vivo-infused luteinized ovaries from animals pretreated to reduce circulating lipoprotein levels, perfused ovaries from a second hormone-primed model, perfused liver from estrogen-treated rats, and isolated and cultured cells from the same ovarian tissues used in the perfusion experiments. The results show that perfused LDL promptly stimulates steroidogenesis. However, the labeled protein moiety of the LDL is not interiorized by the luteal cells, nor is there evidence of LDL protein degradation in the effluent samples. In contrast, internalization of the ligand occurs when luteal cells are incubated with the ligand in vitro. We have observed also that uptake of the 125I-LDL by the ovary can be displaced equally well by excess unlabeled LDL or HDL3. Overall, these experiments suggest that in the intact luteinized ovary, LDL binds to the same sites on the cell surface where HDL "binds," and that LDL cholesterol must be obtained by these steroid hormone-producing cells by a mechanism that does not require internalization of the intact lipoprotein particle.
Response to Letter Regarding Article, “Migraine Intervention With STARFlex Technology (MIST) Trial”
Authors: Andrew Dowson, Michael J. Mullen, Arif Anis Khan, Anthony Rickards, Richard Peatfield, Keith Muir, Christopher Wells, Susan L. Lipscombe, David Hildick-Smith, Trevor Rees, Joseph V. De Giovanni, W. Lindsay Morrison, Giles Elrington, W. Stewart Hillis, Iqbal S. Malik
Journal: Circulation (2009)
CTLA4 polymorphisms and COPD
Authors: A. M. Wood, P. R. Newby, S. C. Gough, R. A. Stockley
Journal: European Respiratory Journal (2010)

We read with interest the article by ZHU et al. [1] describing the association of two single nucleotide polymorphisms (SNPs; rs231775 and rs3087243) within the CTLA4 gene and chronic bronchitis.Both of these polymorphisms may be risk factors for autoimmunity [2], and are often referred to as A49G and CT60, respectively.As alluded to briefly by the authors in their discussion, there has been recent interest in a possible role for autoimmunity in chronic obstructive pulmonary disease (COPD), hence shared genetic susceptibility with other autoimmune diseases would support this hypothesis.Although the authors report their association in two independent cohorts, general acceptance of the importance of this locus would require further validation in other COPD populations.We would like to add support to their results, by reporting association of rs231775 in an a 1 -antitrypsin deficient (a 1 -ATD) cohort, which also tended to associate with the same feature in the 1958 birth cohort.
Understanding mechanisms of novel gene expression in polyploids
Authors: Thomas C. Osborn, J. Chris Pires, James A. Birchler, Donald L. Auger, Z. Jeffery Chen, Hyeon-Se Lee, Luca Comai, Andreas Madlung, R.W. Doerge, Vincent Colot, Robert A. Martienssen
Journal: Trends in Genetics (2003)
Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology
Authors: J. Douglas Rizzo, Alan E. Lichtin, Steven H. Woolf, Jerome Seidenfeld, Charles L. Bennett, David Cella, Benjamin Djulbegovic, Matthew J. Goode, Ann A. Jakubowski, Stephanie J. Lee, Carole B. Miller, Mark U. Rarick, David H. Regan, George P. Browman, Michael S. Gordon
Journal: Blood (2002)
Localization of APOL1 Protein and mRNA in the Human Kidney
Authors: Lijun Ma, Gregory S. Shelness, James A. Snipes, Mariana Murea, Peter A. Antinozzi, Dongmei Cheng, Moin A. Saleem, Simon C. Satchell, Bernhard Banas, Peter W. Mathieson, Matthias Kretzler, Ashok K. Hemal, Lawrence L. Rudel, Snezana Petrovic, Allison Weckerle, Martin R. Pollak, Michael D. Ross, John S. Parks, Barry I. Freedman
Journal: Journal of the American Society of Nephrology (2014)

Although APOL1 gene variants are associated with nephropathy in African Americans, little is known about APOL1 protein synthesis, uptake, and localization in kidney cells. To address these questions, we examined APOL1 protein and mRNA localization in human kidney and human kidney-derived cell lines. Indirect immunofluorescence microscopy performed on nondiseased nephrectomy cryosections from persons with normal kidney function revealed that APOL1 protein was markedly enriched in podocytes (colocalized with synaptopodin and Wilms' tumor suppressor) and present in lower abundance in renal tubule cells. Fluorescence in situ hybridization detected APOL1 mRNA in glomeruli (podocytes and endothelial cells) and tubules, consistent with endogenous synthesis in these cell types. When these analyses were extended to renal-derived cell lines, quantitative RT-PCR did not detect APOL1 mRNA in human mesangial cells; however, abundant levels of APOL1 mRNA were observed in proximal tubule cells and glomerular endothelial cells, with lower expression in podocytes. Western blot analysis revealed corresponding levels of APOL1 protein in these cell lines. To explain the apparent discrepancy between the marked abundance of APOL1 protein in kidney podocytes observed in cryosections versus the lesser abundance in podocyte cell lines, we explored APOL1 cellular uptake. APOL1 protein was taken up readily by human podocytes in vitro but was not taken up efficiently by mesangial cells, glomerular endothelial cells, or proximal tubule cells. We hypothesize that the higher levels of APOL1 protein in human cryosectioned podocytes may reflect both endogenous protein synthesis and APOL1 uptake from the circulation or glomerular filtrate.
The transcription factor XBP-1 is essential for the development and survival of dendritic cells
Authors: Neal N. Iwakoshi, Marc Pypaert, Laurie H. Glimcher
Journal: The Journal of Experimental Medicine (2007)

Dendritic cells (DCs) play a critical role in the initiation, maintenance, and resolution of an immune response. DC survival is tightly controlled by extracellular stimuli such as cytokines and Toll-like receptor (TLR) signaling, but the intracellular events that translate such extracellular stimuli into life or death for the DC remain poorly understood. The endoplasmic reticulum (ER) stress, or unfolded protein response (UPR), is a signaling pathway that is activated when unfolded proteins accumulate in the ER. The most conserved arm of the UPR involves IRE1alpha, an ER transmembrane kinase and endoribonuclease that activates the transcription factor XBP-1 to maintain ER homeostasis and prevent activation of cell death pathways caused by sustained ER stress. We report that XBP-1 is essential for DC development and survival. Lymphoid chimeras lacking XBP-1 possessed decreased numbers of both conventional and plasmacytoid DCs with reduced survival both at baseline and in response to TLR signaling. Overexpression of XBP-1 in hematopoietic progenitors rescued and enhanced DC development. Remarkably, in contrast to other cell types we have examined, the XBP-1 pathway was constitutively activated in immature DCs.
Distribution of congenital melanocytic naevi and congenital naevus-like naevi in a survey of 3406 Italian schoolchildren
Authors: S. Gallus, L. Naldi
Journal: British Journal of Dermatology (2008)

Scanty information is available on the prevalence of congenital melanocytic naevi (CMN) and congenital naevus-like naevi (CNLN), particularly the small ones.To estimate the prevalence of CMN/CNLN in Italian schoolchildren, and to assess variations according to potential risk factors for melanoma.We conducted a survey in 13 Italian areas on 3406 schoolchildren aged 12-17 years. Children were examined by dermatologists who assessed pigmentary traits and made a count of small (6-15 mm in diameter) and medium/large (> 15 mm) CMN/CNLN on 19 anatomical areas.Overall, 592 children (17.4%) had one or more CMN/CNLN. Prevalence of small CMN/CNLN was 16.1%, and that of medium/large CMN/CNLN was 1.8%. There was no difference between age groups and sexes. CMN/CNLN were more frequent in children with a higher number of common melanocytic naevi (multivariate odds ratio, OR = 7.1 for the highest vs. the lowest quartile), consistent in small (OR = 7.2) and medium/large CMN/CNLN (OR = 6.0). Family history of malignant melanoma (OR = 1.4) and personal history of diabetes (OR = 4.4) appeared to be directly, and sun exposure inversely associated with CMN/CNLN. No relation was evident between CMN/CNLN and pigmentary traits, anthropometric characteristics, dietary habits, freckles, sunburns, sunscreen use or history of selected diseases.The association with family history of melanoma, the strong association with acquired melanocytic naevi, and the lack of association with pigmentary traits and sunburns suggest that CMN/CNLN may act as an independent risk marker for subjects at increased risk for cutaneous melanoma later in life.
FT011, a new anti‐fibrotic drug, attenuates fibrosis and chronic heart failure in experimental diabetic cardiomyopathy
Authors: Yuan Zhang, Amanda J. Edgley, Alison J. Cox, Andrew K. Powell, Bing Wang, Andrew R. Kompa, David I. Stapleton, Steven C. Zammit, Spencer J. Williams, Henry Krum, Richard E. Gilbert, Darren J. Kelly
Journal: European Journal of Heart Failure (2012)
THE TREATMENT OF PROGRESSIVE MUSCULAR ATROPHY BY PARATHYROID, CALCIUM, AND VITAMIN D
Authors: T. H. Thomas
Journal: BMJ (1928)

VARICOSE veins are mnet with in meen and women in all grades of society, but varicose ulcer is almost entirely con- fined to tihe wives of working-class meni-womeln who, as a r1ul;e, have had large families, and who have to work all the vaking hours all the days of their lives.So inured are some of these womiieni to the paini that they hesitate to have the ulcer healed lest some other and greater mis- fortulle slhould overtake them.Our exl)erience, gained during the past twelve -months, sihows that most ulcers of the leg can be healed, and over1GO per cent.can be cured; it favours -a special clinic for ulcers of the leg, si-nce it is difficult: to give these patients the attention they require in the ordinary course of a nmixed clinlic.In each case of chronic ulcer a complete history is takell and a description of the ulcer is recorded for future refer- eiine.Tho Wassermann reaction is always determined, and should this be positive appropriate -treatment is given.Var'icose, veins are treated by injection and their cure has rendered the prognosis for varicose ulcer much better than formerly.I-NJRCTON OF VARICOSE VEQNS.This operation is performed in-the -out-patient clinicJ and the following solutionsare used.
Efficacy of riociguat in patients with inoperable CTEPH vs persistent/recurrent PH after pulmonary endarterectomy (PEA): Results from the phase III CHEST-1 study
Authors: Eckhard Mayer, Andrea M. D'Armini, Hossein-Ardeschir Ghofrani, Ekkehard Grünig, Pavel Jansa, Nick H. Kim, Gerald Simonneau, Adam Torbicki, Chen Wang, Martin R. Wilkins, Neil Davie, Arno Fritsch, Marius M. Hoeper
Journal: European Respiratory Journal (2013)

Background 

In CHEST-1, riociguat significantly improved several clinically relevant endpoints in CTEPH patients (pts).

Aims 

Here we describe and compare its clinical effect in subgroups of pts with inoperable and persistent/recurrent CTEPH.

Methods 

Pts (34% male, mean age 59 y) received placebo (pbo) or riociguat (up to 2.5 mg tid) for 16 wks. The primary endpoint was change in 6MWD; secondary endpoints were change in PVR, NT-proBNP, WHO functional class (FC), time to clinical worsening, Borg dyspnea score, and EQ-5D and Living with PH (LPH) questionnaires.

Results 

At baseline (BL), inoperable pts had lower 6MWD (341±80 vs 363±76 m) and higher PVR (861±452 vs 595±233 dyn·s·cm-5) and NT-proBNP (1732±2690 vs 1100±1150 pg/mL) vs persistent/recurrent pts. Selected endpoints and safety data are shown below.

View this table:



Conclusions 

Riociguat improved primary and secondary endpoints in both pts with inoperable and pts with persistent/recurrent CTEPH vs BL, with a more marked effect in inoperable pts.
All trials must be registered and the results published
Authors: I. Chalmers, P. Glasziou, F. Godlee
Journal: BMJ (2013)

The term “dysfunction” defines the motor disorders of the gall bladder and the sphincter of Oddi (SO) without note of the potential etiologic factors for the difficulty to differentiate purely functional alterations from subtle structural changes. Dysfunction of the gall bladder and/or SO produces similar patterns of biliopancreatic pain and SO dysfunction may occur in the presence of the gall bladder. The symptom-based diagnostic criteria of gall bladder and SO dysfunction are episodes of severe steady pain located in the epigastrium and right upper abdominal quadrant which last at least 30 minutes. Gall bladder and SO dysfunctions can cause significant clinical symptoms but do not explain many instances of biliopancreatic type of pain. The syndrome of functional abdominal pain should be differentiated from gall bladder and SO dysfunction. In the diagnostic workup, invasive investigations should be performed only in the presence of compelling clinical evidence and after non-invasive testing has yielded negative findings. Gall bladder dysfunction is suspected when laboratory, ultrasonographic, and microscopic bile examination have excluded the presence of gallstones and other structural abnormalities. The finding of decreased gall bladder emptying at cholecystokinin-cholescintigraphy is the only objective characteristic of gall bladder dysfunction. Symptomatic manifestation of SO dysfunction may be accompanied by features of biliary obstruction (biliary-type SO dysfunction) or significant elevation of pancreatic enzymes and pancreatitis (pancreatic-type SO dysfunction). Biliary-type SO dysfunction occurs more frequently in postcholecystectomy patients who are categorized into three types. Types I and II, but not type III, have biochemical and cholangiographic features of biliary obstruction. Pancreatic-type SO dysfunction is less well classified into types. When non-invasive investigations and endoscopic retrograde cholangiopanreatography show no structural abnormality, manometry of both biliary and pancreatic sphincter may be considered.
T cell-derived antigen binding molecules play a role in the induction of airway hyperresponsiveness.
Authors: J Garssen, F P Nijkamp, E Van Vugt, H Van der Vliet, H Van Loveren
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We previously demonstrated that tracheal hyperreactivity (in vitro) and altered lung functions (in vivo) were induced during a delayed-type hypersensitivity (DTH) reaction in murine lungs. These alterations were transferable with T cells, suggesting that this animal model could be used as a model for cellular IgE-independent immunity. In the present study we demonstrated that depletion of T suppressor/cytotoxic cells failed to abolish the ability of transferred cells to induce hyperresponsiveness. Depletion of T helper cells partially inhibited the induction of hyperreactivity. Depletion of 14-30+ cells (the monoclonal antibody 14-30 reacts with a common isotype of T cell-derived antigen binding molecules [TABM] that can arm mast cells) completely abolished the ability to transfer hyperreactivity. The cromoglycate-like antiasthmatic drug nedocromil, which stabilizes mast cells, inhibited the induction of T cell-mediated hyperresponsiveness. Moreover, in mast cell-deficient mice, T cell-mediated hyperresponsiveness can be less induced compared with normal littermates. These experiments indicate that mast cells play at least a partial role in the induction of airway hyperresponsiveness in this model. Dexamethasone, a well-known inhibitor of phospholipase A2, inhibited the T cell-mediated hyperresponsiveness, whereas the cyclooxygenase inhibitor suprofen did not. This indicated that arachidonic acid metabolites, but not cyclooxygenase products, play a role in the induction of T cell-mediated hyperreactivity. Pretreatment with the lipoxygenase inhibitor AA-861 significantly inhibited the induction of tracheal hyperreactivity. Platelet-activating factor appeared not to be involved in the induction of hyperresponsiveness in this model, because the platelet-activating factor antagonist WEB 2170 failed to abolish the induction of T cell-mediated hyperreactivity. Intravenous injection of purified mast cell-arming TABM, followed by intranasal hapten challenge 30 min later, resulted in increased vascular permeability 2 h after challenge, which is characteristic of the early initiating phase of DTH. In addition, tracheal hyperreactivity (in vitro) and altered lung functions (in vivo) were observed 2 h after challenge. From these data we conclude that airway hyperreactivity and altered lung functions are induced by early steps in the cellular cascade of DTH.
Psychosis alters association between IQ and future risk of attempted suicide: cohort study of 1 109 475 Swedish men
Authors: G. D. Batty, E. Whitley, I. J. Deary, C. R. Gale, P. Tynelius, F. Rasmussen
Journal: BMJ (2010)

<b>Objectives</b> To explore associations between IQ measured in early adulthood and subsequent hospital admissions for attempted suicide and to explore the role of psychosis and examine associations of IQ with specific methods of attempted suicide. <b>Design</b> Cohort study. <b>Setting</b> Sweden. <b>Participants</b> 1 109 475 Swedish men with IQ measured in early adulthood followed up for an average 24 years. <b>Main outcome measures</b> Hospital admission for attempted suicide. <b>Results</b> 17 736 (1.6%) men had at least one hospital admission for attempted suicide by any means during follow-up. After adjustment for age and socioeconomic status, lower IQ scores were associated with an elevated risk of attempted suicide by any means (hazard ratio per standard deviation decrease in IQ=1.57, 95% confidence interval 1.54 to 1.60), with stepwise increases in risk across the full IQ range (P for trend&lt;0.001). Similar associations were observed for all specific methods of attempted suicide. Separate analyses indicated that associations between IQ and attempted suicide were restricted to participants without psychosis and that IQ had no marked impact on risk of attempted suicide in those with psychosis. <b>Conclusions</b> Low IQ scores in early adulthood were associated with a subsequently increased risk of attempted suicide in men free from psychosis. A greater understanding of the mechanisms underlying these associations may provide opportunities and strategies for prevention.
Mineralocorticoid Effects in the Kidney
Authors: Olivier G. Muller, Rimma G. Parnova, Gabriel Centeno, Bernard C. Rossier, Dmitri Firsov, Jean-Daniel Horisberger
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Aldosterone exerts its effects through interactions with two types of binding sites, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors. Although both receptors are known to be involved in the anti-natriuretic response to aldosterone, the mechanisms of signal transduction leading to modulation of electrolyte transport are not yet fully understood. This study measured the Na<sup>+</sup> and K<sup>+</sup> urinary excretion and the mRNA levels of three known aldosterone-induced transcripts, the serum and glucocorticoid-induced kinase (Sgk-1), the α subunit of the epithelial Na<sup>+</sup> channel (αENaC), and the glucocorticoid-induced-leucine-zipper protein (GILZ) in the whole kidney and in isolated cortical collecting tubules of adrenalectomized rats treated with low doses of aldosterone and/or dexamethasone. The resulting plasma concentrations of both steroids were close to 1 nmol/L. Aldosterone, given with or without dexamethasone, induced anti-natriuresis and kaliuresis, whereas dexamethasone alone did not. GILZ and αENaC transcripts were higher after treatment with either or both hormones, whereas the mRNA abundance of Sgk-1 was increased in the cortical collecting tubule by aldosterone but not by dexamethasone. We conclude the increased expression of Sgk-1 in the cortical collecting tubules is a primary event in the early antinatriuretic and kaliuretic responses to physiologic concentrations of aldosterone. Induction of αENaC and/or GILZ mRNAs may play a permissive role in the enhancement of the early and/or late responses; these effects may be necessary for a full response but do not by themselves promote early changes in urinary Na<sup>+</sup> and K<sup>+</sup> excretion. E-mail: Jean-Daniel.Horisberger@ipharm.unil.ch
MOLECULAR MECHANISMS OF VITAMIN E TRANSPORT
Authors: Maret G. Traber, Hiroyuki Arai
Journal: Annual Review of Nutrition (1999)

▪ Abstract If the function of vitamin E is that of an antioxidant and the various forms of vitamin E have similar antioxidant activities, then why does RRR-α-tocopherol have the highest biologic activity? This chapter describes how interactions by investigators from various scientific disciplines using stable isotopes, molecular biology tools, and sophisticated genetic studies of humans with vitamin E deficiency have led to an understanding of this problem. This chapter provides an overview of (a) studies using deuterated tocopherols that demonstrated that the plasma preference for α-tocopherol is dependent on metabolic processes in the liver; (b) the isolation, molecular biology, and function of the α-tocopherol transfer protein; and (c) studies that demonstrated that patients who were vitamin E deficient as a result of no known cause had defective α-tocopherol transfer protein genes. Finally, we focus on the future—what remains to be learned about the regulation of vitamin E in tissues.