tbuckley/cabot-search huggingface dataset:
The vitamin D<sub>3</sub>receptor and retinoid X receptors in psoriatic skin: the receptor levels correlate with the receptor binding to DNA
Authors: None Jensen, None Sørensen, None Sølvsten, None Kragballe
Journal: British Journal of Dermatology (1998)

It is unknown whether vitamin D3 analogues improve psoriasis by overcoming an intrinsic abnormality of the vitamin D3 signalling pathway in psoriatic skin. The effects of vitamin D3 are mediated through the vitamin D3 receptor (VDR). The VDR heterodimerizes with another transcriptional regulator, preferentially the retinoid X receptor (RXR). In the present study the levels of VDR and RXR in involved and uninvolved psoriatic skin were determined by immunoblotting, and the binding of the VDR–RXR complex to a vitamin D3 response element (VDRE) consisting of two hexanucleotides spaced by three nucleotides (DR-3) by the electrophoretic mobility shift assay. The levels of VDR were similar in involved and uninvolved skin. RXRα, but neither RXRβ nor RXRγ, was detectable. The RXRα levels were slightly lower in involved psoriatic skin than in uninvolved psoriatic skin, but this difference was statistically insignificant. The binding of VDR–RXR to the DR-3 VDRE was similar in uninvolved and involved psoriatic skin. Furthermore, there was a strong linear correlation between the levels of both VDR and RXRα and their binding to DNA. In conclusion, the initial part of the vitamin D3 signalling pathway involving receptor levels and receptor binding to DNA is normal in involved psoriatic skin.
DNA synthesis is not necessary for osteoclastic responses to parathyroid hormone in cultured fetal rat long bones.
Authors: J A Lorenzo, L G Raisz, J M Hock
Journal: Journal of Clinical Investigation (1983)

Osteoclasts, the principal cells mediating bone resorption, are believed to increase their size, number, and resorbing activity in response to parathyroid hormone (PTH) through mechanisms dependent upon the fusion of specific mononuclear precursor cells into either new or existing multinucleated osteoclasts. To address the question of whether these actions of PTH are dependent on the replication of osteoclast precursor cells, we examined the ability of an inhibitor of DNA synthesis, hydroxyurea (HU), to alter bone resorption, osteoclast formation, and DNA synthesis in cultured fetal rat bones treated with PTH. We found that HU significantly reduced [3H]thymidine incorporation into the bones and labeling of osteoclast nuclei by greater than 90%, but did not prevent PTH from stimulating bone resorption, measured as the release of 45Ca, or from increasing the number of osteoclasts in the bones. In bones cultured without PTH, HU decreased the rate of bone resorption, but not the number of osteoclasts per bone. We conclude that in fetal rat bone cultures, PTH can increase osteoclast number and stimulate bone resorption by affecting existing osteoclasts and osteoclast precursors, and that replication of osteoclast precursor cells is not necessary for PTH to stimulate a resorptive response. In unstimulated cultures it appears that HU inhibits bone resorption by affecting mechanisms that are independent of changes in osteoclast number and that may be influenced by cell replication or other unknown factors.
NHS trust faces bill for compensation in home takeover
Authors: C. Dyer
Journal: BMJ (1995)

An NHS trust that plans to turn a house in a residential street into sheltered accommodation for five psychiatric patients could face a massive claim for compensation from neighbouring home owners after a High Court ruling last week. Mr Justice Chadwick refused six residents of Southwell Park Road in Camberley, Surrey, an injunction to stop Heathlands NHS Trust's sheltered housing scheme, but he ruled that they can seek compensation for any reduction in their homes' value when the patients move in.

The judgment clarifies an obscure area of the law and …
Abstract 4103: Sphingosine kinase-1 mediates LPA-induced gastric cancer cell proliferation
Authors: Subramaniam Ramachandran, Dai Shida, Masayuki Nagahashi, Sheldon Milstien, Sarah Spiegel, Kazuaki Takabe
Journal: Cancer Research (2010)

Abstract The lysophospholipids, lysophosphatidic acid (LPA) and sphingosine-1 phosphate (S1P) are important mediators of a variety of biological processes important for maintenance and progression of cancer. Autotaxin and sphingosine kinase 1 (SphK1), the enzymes responsible for synthesis of LPA and S1P, respectively, are elevated in many cancer types. We previously reported that LPA markedly enhanced SphK1 and S1P3 receptor mRNA levels, transactivated EGFR, and caused migration in MKN-1 gastric cancer cells [Shida et al., Cancer Res. 68:6569, 2008]. We have now shown that LPA potently stimulates proliferation of MKN-1 cells and downregulation of SphK1 or treatment with the isozyme-specific SphK1 inhibitor, SK1-I, markedly reduced LPA-mediated proliferation. The signaling pathways responsible for LPA-induced SphK1 upregulation were also investigated. U0126, a MEK1/2 inhibitor, completely abrogated LPA-induced elevation of SphK1 mRNA, while inhibitors of PI3K, protein kinase C, p38, JNK or NF-κB did not have an effect. Additionally, siRNA mediated downregulation of ERK2, but not AKT 1 or Akt2, blocked LPA-mediated SphK1 mRNA increase. These results were further confirmed by adenoviral expression of dominant negative MEK1, which inhibited LPA-induced SphK1 upregulation, while constitutively active MEK1 increased basal SphK1 mRNA levels. Furthermore, adenoviral expression of dominant negative or constitutively active AKT1 also did not change SphK1 mRNA levels. Our data implicate ERK2 as an important mediator of LPA signaling and upregulation of SphK1 and additionally, point to SphK1 and S1P production as potential therapeutic targets in gastric cancer. This work was supported by NCI grant R01CA61774 to SS and NIH grant 5K12HD055881 and Susan G. Komen for the Cure Research Foundation Career Catalyst Research Grant KG090510 to KT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4103.
Wales publishes waiting times for diagnostic tests
Authors: Roger Dobson
Journal: BMJ (2006)

More than 2000 patients in Wales have been waiting longer than 36 weeks for radiology tests, and almost 4000 have been waiting the same length of time to see a foot specialist.

The figures were published by the Welsh Assembly, which said that Wales was the first UK country to publish waiting times for diagnostic tests and various types of therapy such as occupational therapy and speech therapy.

The figures show that overall around 85% of patients have been waiting less than 36 weeks for investigations and therapy services—the target waiting time set for March …
The role of angiogenesis in rheumatoid arthritis: recent developments
Authors: A. E. Koch
Journal: Annals of the Rheumatic Diseases (2000)

Rheumatoid arthritis (RA) is characterised by synovial tissue leucocyte ingress and angiogenesis, or new blood vessel growth.1-8 The disease is thought to occur as an immunological response to an as yet unidentified antigen. Even in early RA, some of the earliest histological observations are blood vessels.9 A mononuclear infiltrate characterises the synovial tissue along with a luxuriant vasculature. Angiogenesis is integral to formation of the inflammatory pannus and without angiogenesis, leucocyte ingress could not occur.

Angiogenesis is regulated by a complex set of inducers and inhibitors. In this paper we will present representative examples of both angiogenesis inducers and inhibitors that may regulate RA neovascularisation (fig 1). In inflammatory states like RA, angiogenesis inducers outweigh angiogenesis inhibitors.



Figure 1 
Balance of angiogenesis inducers and inhibitors in inflammatory states such as rheumatoid arthritis.



### ENDOGLIN AS AN ANGIOGENIC MEDIATOR

There are a number of angiogenesis inducers that may play a part in RA. Among these are endoglin, an endothelial glycoprotein, which contains an arginine-glycine-aspartic acid (RGD) motif, and also acts as an adhesion molecule.10 11 Endoglin is a receptor for transforming growth factor β. Mice lacking the endoglin gene die from defective vascular development.12 We have shown that endoglin is upregulated in RA synovial endothelial cells compared with normal synovial tissue endothelial cells.13 

### VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)

An angiogenic mediator that has attracted much attention recently is VEGF, which is an endothelial selective growth factor.14 VEGF induces vascular permeability as well.15 In human RA, several groups have described VEGF in the joints and serum of RA patients.16-23 VEGF is inducible by hypoxia, which may occur in the inflamed joint.17 24 Hypoxia inducible factor-1 (HIF-1), which is made of HIF-1α, and hydroxycarbon nuclear translocator (ARNT), contols many transciptional responses to hypoxia by binding to hypoxia response elements of target genes like the VEGF gene.25 …
Open access, and proud of it
Authors: Fiona Godlee
Journal: BMJ (2005)

You're wrong more often than you think On page 781, Klein discusses five examples of cognitive biases that can affect medical decision making and offers suggestions for avoiding them.Psychologists have extensively studied the cognitive processes involved in decision making, and the biases that lead to making poor decisions are widespread, even among doctors.It is possible to train yourself to watch for these errors.Among the strategies for good decision making are to consider whether data are truly relevant and to ask questions that would disprove, rather than confirm, your current hypothesis.
Abstract 1970: Liposomal nanoparticle siRNA delivery systems for <i>in vivo</i> silencing of the androgen receptor in human prostate cancer
Authors: Kevin X. Zhang, Justin B. Lee, Yuen Yi C. Tam, Ying K. Tam, Pieter R. Cullis, Paul S. Rennie
Journal: Cancer Research (2012)

Abstract Prostate cancer is the most commonly diagnosed non-skin cancer in men and one of the leading causes of cancer-death. While frequently curable by surgical or radiation ablation, recurrent or metastatic disease is usually managed with androgen withdrawal therapies (medical castration), which block the growth promoting effects of androgens on the androgen receptor (AR). Unfortunately, the cancers eventually progress to the lethal castration-resistant state. Previously, we reported that knocking down the AR by RNA interference using small hairpin RNA (shRNA) inhibits this progression and, in about 50% of tumours, causes complete regression. In this study, we investigated the ability of small interfering RNA (siRNA) encapsulated in lipid nanoparticle (LNP) to silence AR in human prostate cancer cell lines and xenograft tumours following intravenous injections. In vitro screening studies with prostate cancer cell lines using a panel of cationic lipids demonstrated that siRNA formulated in LNPs containing the ionizable cationic lipid 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-KC2-DMA) exhibited the most potent AR silencing effects. This is attributed to an optimized ability of DLin-KC2-DMA-containing LNP to enter into cells and to release the siRNA into the cell cytoplasm following endocytotic uptake. DLin-KC2-DMA LNPs were also effective in silencing the AR in a wild-type AR expressing cell line, LAPC-4, and a variant AR expressing cell line, CWR22Rv1. Importantly, we found that LNP AR-siRNA systems containing DLin-KC2-DMA could silence AR gene expression in distal LNCaP xenograft tumors and decrease serum PSA levels following intravenous injection. The 5′RACE experiments further confirmed that siRNA-induced specific cleavage of AR mRNA was the primary mechanism of action. In conclusion, these results indicate that in vivo delivery of siRNA to knockdown AR using our LNP formulations causes a decrease in serum PSA and provides proof in principle that this approach may offer a therapeutic strategy for treating advanced prostate cancer. (Funded by Canadian Institutes for Health Research and a PCF-STAR Project from Prostate Cancer Canada with the support of Safeway Canada) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1970. doi:1538-7445.AM2012-1970
TCT-303 The Geometric Effect of Aortic Stenosis On Aortoventricular Interface Anatomy As Assessed By Multi-detector Computerised Tomographic Imaging.
Authors: Robert Gooley, James Cameron, Sonia Ciavarella, Siobhan Lockwood, Paul Antonis, Ian T. Meredith
Journal: Journal of the American College of Cardiology (2014)
Mechanical Dispersion Assessed by Myocardial Strain in Patients After Myocardial Infarction for Risk Prediction of Ventricular Arrhythmia
Authors: Kristina H. Haugaa, Marit Kristine Smedsrud, Torkel Steen, Erik Kongsgaard, Jan Pål Loennechen, Terje Skjaerpe, Jens-Uwe Voigt, Rik Willems, Gunnar Smith, Otto A. Smiseth, Jan P. Amlie, Thor Edvardsen
Journal: JACC. Cardiovascular imaging (2010)
Treating Disseminated Mycobacterium avium-intracellulare Infection
Authors: Michael C. Bach
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 January 1989Treating Disseminated Mycobacterium avium-intracellulare InfectionMichael C. Bach, MDMichael C. Bach, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-2-169 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Studies (1, 2) have recently suggested that disseminated Mycobacterium avium-intracellulare infection in patients with the acquired immunodeficiency syndrome (AIDS) should not be treated because current therapy is of no proven value and is potentially toxic. My experience with four cases of M. avium-intracellulare in patients with AIDS suggests that a significant improvement in symptomatology can be achieved by therapy.A 31-year-old homosexual man had fevers, sweats, and weight loss 9 months afterPneumocystis cariniipneumonia. DisseminatedM. avium-intracellularewas documented by positive blood cultures as well as by increased nodal uptake of gallium-67 citrate. Treatment of the...References1. MacherKovacsGill AJV. Bacteremia due to Mycobacterium avium-intracellulare in the acquired immunodeficiency syndrome. Ann Intern Med. 1983;99:782-5. LinkGoogle Scholar2. ArmstrongGoldDryjanski DJJ. Treatment of infections in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1985;103:738-43. LinkGoogle Scholar3. Young L. Mycobacterium avium complex infection. J Infect Dis. 1988;157:863-7. CrossrefMedlineGoogle Scholar4. MasurTuazonGill HCV. Effect of combined clofazimine and ansamycin therapy on Mycobacterium avium-intracellulare bacteremia in patients with AIDS. J Infect Dis. 1987;155:127-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Maine Medical Center Portland, ME 04102 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe Respiratory SystemMycobacterial Disease in Patients with HIV InfectionMycobacteriosis and Nocardiosis in the Immunocompromised HostTreatment and developmental therapeutics of Mycobacterium avium complex (MAC) infectionsThe Mycobacterium avium complexTreatment of Mycobacterium avium Complex Bacteremia in AIDS with a Four-Drug Oral Regimen Rifampin, Ethambutol, Clofazimine, and CiprofloxacinCarol A. Kemper, MD, Tze-Chiang Meng, MD, Joseph Nussbaum, MD, Joseph Chiu, MD, David F. Feigal, MD, Angie E. Bartok, MPH, John M. Leedom, MD, Jeremiah G. Tilles, MD, Stanley C. Deresinski, MD, J. Allen McCutchan, MD, California Collaborative Treatment GroupTuberculosis And Nontuberculous Mycobacterial DiseaseClofazimine: A Review of its Use in Leprosy and Mycobacterium Avium Complex Infection 15 January 1989Volume 110, Issue 2Page: 169-170KeywordsAIDSBloodFeversHomosexualsMycobacterium avium complexPneumocystis carinii pneumoniaSweatWeight loss Issue Published: 15 January 1989 PDF DownloadLoading ...
Prostaglandin Inhibitors
Authors: James R. Dingfelder
Journal: New England Journal of Medicine (1982)

Dysmenorrhea and premenstrual tension are afflictions that occasionally receive renewed interest as a result of changes in both scientific and social understanding. The clinical introduction of a rapidly growing number of prostaglandin synthetase inhibitors came during a decade when feminists had been increasingly critical about existing psychophysiologic explanations for these disorders. These developments promoted a receptive atmosphere for new clinical and basic investigations aimed at a therapeutic resolution of both conditions. The designations "primary dysmenorrhea syndrome" and "premenstrual syndrome" reflect a recent tendency of many physicians to regard both conditions as a constellation of symptoms and not merely as menstrual . . .
Nifedipine in the treatment of chilblains.
Authors: P M Dowd, M H Rustin, S Lanigan
Journal: BMJ (1986)

<h3>Abstract</h3> Bacteria regulate their cellular resource allocation to enable their fast growth-adaptation to a variety of environmental niches. We studied the ribosomal allocation, growth and expression profile of two sets of fast-growing mutants of <i>Escherichia coli</i> K-12 MG1655. Mutants with 3 copies of the stronger ribosomal RNA operons grew faster than the wild-type strain in minimal media and show similar phenotype to previously studied <i>rpoB</i> mutants. All of them displayed increased ribosomal content, a longer diauxic shift and a reduced activity of the <i>aceBAK</i> operon, indicative of repressed gluconeogenic pathways. Transcriptomic profiles of fast-growing mutants showed common downregulation of hedging functions and upregulated growth functions. Proteome allocation estimations showed an increase in the growth-related proteome for fast-growing strains, but not an increased cellular budget for recombinant protein production. These results show that two different regulatory perturbations (rRNA promoters or <i>rpoB</i> mutations) increasing ribosomal allocation optimize the proteome for growth with a concomitant fitness cost. <h3>Highlights</h3> Strains with the 3 stronger ribosomal operons grow faster than the wild-type Fast-growing strains show higher ribosomal content Comparison among <i>rrn</i> and RNAP mutants shows commonalities Fast-growing strains show adaptation trade-offs Mutant’s proteome is larger and optimized for growth
ARTIFICIAL ACTIVATION OF THE GROWTH IN VITRO OF CONNECTIVE TISSUE
Authors: Alexis Carrel
Journal: The Journal of Experimental Medicine (1913)

The experiments have shown that extracts of tissues and tissue juices, under certain conditions, accelerate the growth in intro of the connective tissue from about three to forty times. This activating power was found in many tissues. It was much more marked, however, with the extracts of embryos, of adult spleen, and of the Rous sarcoma. The power diminished directly with the dilution of the extracts, and appeared not to apply to the tissues of a heterologous animal. The power was reduced when heated at 56 degrees C., and removed when heated at 70 degrees C. It was diminished markedly by filtration through a Berkefield filter and was completely suppressed by filtration through a Chamberland filter. Possibly the finding of the activating power of tissue extracts will have no immediate practical application. Nevertheless, it may be indirectly useful by leading to the discovery of some of the factors determining the growth of tissues and of the unknown laws of cell dynamics, and may ultimately throw light on the mechanism of the cicatrization of wounds.
Cyclophosphamide Therapy in Wegener's Granulomatosis
Authors: Stuart N. Novack, Carl M. Pearson
Journal: New England Journal of Medicine (1971)

Four adults suffering from Wegener's granulomatosis, each with extensive pulmonary and Central-nervous-system involvement and lesser degrees of renal disease and sinusitis, were treated with cyclophosphamide. Each had previously proved unresponsive to corticosteroid therapy. Cyclophosphamide was given in massive dosages intravenously in one near terminal patient and orally in three others. In all four patients a rapid amelioration of all signs, symptoms and evidence of disease occurred. Pulmonary lesions, even cavitary ones, resolved, as did a diffuse and extensive pulmonary infiltrate in one patient. Neurologic and renal lesions diminished or were completely reversed. In two of the four patients it was possible to omit all therapy for 12 to 20 months, without evidence of recurrence of disease. The other two patients have been asymptomatic for 3 1/2 years on continued low-dose cyclophosphamide. The uniformly good results in this series imply effective immunosuppression, even in an ongoing disease. Further trials appear warranted.
Giving advice about welfare benefits in general practice
Authors: B. Jarman
Journal: BMJ (1985)

Many people do not receive the full state welfare benefits to which they are entitled. Roughly two thirds of the population consult their general practitioners at least once a year. General practitioners and community nurses are exceptionally well placed to detect those who are suffering genuine financial hardship but they are not well equipped to give advice about the complex system of state social security benifits. Imparting such advice in suitable cases, particularly where the lack of it is detrimental to health, might be regarded as a proper function of general practitioners and health centres. A method of providing such advice in a health centre with the help of a computer is described.
A MAJOR GAP EXISTS IN APPLYING PUBLISHED GUIDELINES FOR PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH WITH UNDERUTILIZATION OF DEVICE IMPLANTATION; AN ESCAPE DATABASE ANALYSIS
Authors: Emad F. Aziz, Chaithanya K. Pamidimukala, Balaji Pratap, Joseph H. Bastawrose, Terrence Park, Michael Hanna, Kultida Tangwongchai, Urvi Pai, Darcie Alwood, Chelsea Rittenhouse, Akitto Ledda, Fahad Javed, Eyal Herzog
Journal: Journal of the American College of Cardiology (2012)
Efficacy of circumferential pulmonary vein ablation in patients with atrial fibrillation and associated heart failure
Authors: Carlo Pappone, Salvatorre Rosanio, Giuseppe Augello, Simone Gulletta, Cosimo Dicandia, Patrizio Mazzone, Alessia Pappone, Gabriele Paglino, Mario Pittalis, Gabriele Vicedomini
Journal: Journal of the American College of Cardiology (2003)
Cesarean Section Rates-Reply
Authors: Randall S. Stafford
Journal: JAMA (1991)

In Reply.—  My original article 1 in JAMA outlined strategies proposed to control rising cesarean section rates. That article, as well as my response 2 to a letter advocating the universal application of cesarean section, suggested that further increases in cesarean section use contradict a consensus of research. This body of research, despite occasional limitations, should help obstetricians confront the clinical dilemmas mentioned by Dr Peach.  There is little controversy that adverse maternal outcomes are more common following cesarean section. Women undergoing cesarean section have higher mortality, higher rates of postpartum infection, longer hospital stays, and longer recovery periods. Although data specifically addressing the outcome of elective cesarean section are limited, adverse maternal outcomes are more common with cesarean section both before and after the onset of labor.  The review article 3 cited in my letter concluded that a conservative estimate of the risk of maternal mortality from a cesarean