tbuckley/cabot-search huggingface dataset:
Hypoxia and STAT3 signalling interactions regulate pro-inflammatory pathways in rheumatoid arthritis
Authors: Wei Gao, Jennifer McCormick, Mary Connolly, Emese Balogh, Douglas J Veale, Ursula Fearon
Journal: Annals of the Rheumatic Diseases (2014)

Objective To examine the effect of hypoxia on Signal Transducer and Activator of Transcription 3 (STAT3)-induced pro-inflammatory pathways in rheumatoid arthritis (RA). Methods Detection of phospho-STAT3 was assessed in RA synovial tissue and fibroblasts (RASFC) by immunohistology/immunofluorescence. Primary RASFCs and a normal synoviocyte cell line (K4IM) were cultured under hypoxic and normoxic conditions±Stat3-siRNA, HIF-siRNA or WP1066 (JAK2-inhibitor). HIF1α, p-STAT3, p-STAT1 and Notch-1IC protein expression were analysed by western blot. Functional mechanisms were quantified by invasion chamber, matrigel and migration assays. IL-6, IL-8, IL-10 and matrixmetalloproteinases (MMP)-3 were quantified by ELISA. Notch-1 receptor, its DLL-4 ligand and downstream target genes ( hrt-1 , hrt-2 ) were quantified by real-time PCR. The effect of WP1066 on spontaneous secretion of pro/anti-inflammatory cytokines and Notch signalling was examined in RA synovial explants ex vivo. Results p-STAT3 was increased in RA synovium compared with control (p&lt;0.05). Hypoxia induced p-STAT3, p-STAT1 and HIF1α expression, an effect blocked by Stat3-siRNA and WP1066. Hypoxia-induced cell invasion, migration and cytokine production were inhibited by Stat3-siRNA (p&lt;0.05) and WP1066 (p&lt;0.05). While HIF1α siRNA inhibited hypoxia-induced p-STAT3 detection, Stat3-siRNA also inhibited hypoxia-induced HIF1α. Furthermore, hypoxia-induced Notch-1IC, DLL4, hrt-1 and -2 expression were significantly inhibited by WP1066 (p&lt;0.05). Finally, in RA synovial explant cultures ex vivo, WP1066 decreased spontaneous secretion of IL-6, IL-8 and MMP3 (p&lt;0.05), Notch-1 mRNA (p&lt;0.05) and induced IL-10 (p&lt;0.05). Conclusions This is the first study to provide evidence of a functional link between HIF1α, STAT3 and Notch-1 signalling in the regulation of pro-inflammatory mechanisms in RA, and further supports a role for STAT blockade in the treatment of RA.
Too early to declare H1N1 swine flu pandemic over, says WHO chief
Authors: J. Zarocostas
Journal: BMJ (2009)

It is too soon to declare the H1N1 swine flu pandemic over and the evolution of the virus should be monitored closely over the next year, the head of the World Health Organization has warned.

Many countries in the northern hemisphere—such as the US, Canada, the United Kingdom, and some parts of continental Europe—“have passed the peak of their second wave,” Dr Margaret Chan, director general of the WHO, told reporters on Tuesday. But there is still intense pandemic influenza activity in countries such as India and Egypt, she said.

“I think it is too premature and too early for us to say we have come …
Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma
Authors: N. Nieto-Rementería, G. Pérez-Yarza, M.D. Boyano, A. Apraiz, R. Izu, J.L. Díaz-Pérez, A. Asumendi
Journal: British Journal of Dermatology (2008)

Bexarotene is the first synthetic retinoid X receptor-selective retinoid (rexinoid) approved for the treatment of cutaneous T-cell lymphoma (CTCL). However, little is known about the signalling pathways by which it exerts its anticarcinogenic effect.To characterize the effects of bexarotene in CTCL cell lines and elucidate the underlying molecular pathways of its antineoplastic effect.The cell lines Hut-78, HH and MJ were used. Cell viability was assessed with the XTT assay. The self-renewal potential of cells after bexarotene treatment was studied with the methylcellulose clonogenic assay. Flow cytometry was used to analyse the effects on cell cycle, Ki-67 expression and apoptosis induction. Cell cycle and apoptosis-related protein expression were determined by Western blot and immunofluorescence.Bexarotene induced a loss of viability and more pronounced inhibition of clonogenic proliferation in HH and Hut-78 cells, whereas the MJ line exhibited resistance. Bexarotene upregulated and activated Bax in sensitive lines, although not enough to signal significant apoptosis. Instead, all data point to the inhibition of proliferation, rather than apoptosis, as the main mechanistic action of the rexinoid. Bexarotene signals both G(1) and G(2)/M arrest by the modulation of critical checkpoint proteins. We further found that bexarotene activates p53 by phosphorylation at Ser15, which influences the binding of p53 to promoters for cell cycle arrest, induces p73 upregulation, and, in concordance, also modulates some p53/p73 downstream target genes, such as p21, Bax, survivin and cdc2. Bexarotene-mediated ataxia telangiectasia mutated protein (ATM) activation in all studied lines suggests that ATM is likely to be the p53/p73 upstream activator.Our data indicate for the first time that bexarotene exerts its effect in CTCL mainly by triggering the p53/p73-dependent cell cycle inhibition pathway, probably by upstream ATM activation. Therefore, bexarotene-modulated genes represent potential biomarkers to assess the response to treatment of patients with CTCL.
Light- and electron-microscopical study of a case of gold salt—induced hepatotoxicity
Authors: Gerald M. Fleischner, Rachel Morecki, Takamasa Hanaichi, Hisao Hayashi, Nelson Quintana, Irmin Sternlieb
Journal: Hepatology (1991)

A 56-yr-old woman with long-standing rheumatoid arthritis exhibited jaundice, pruritus and abdominal discomfort after 8 yr of periodic gold sodium thiomalate injections amounting to a cumulative dose in excess of 2.5 gm. Histopathological examination of the liver biopsy specimen showed submassive loss of parenchyma, collapse of reticulin and mixed cellular inflammatory infiltrates. Macrophages contained dark granules, which displayed the characteristics of aurosomes when examined by transmission electron microscopy and electron microprobe analysis. It is likely that hepatocellular injury occurred when the lysosomal storage capacity for gold was exceeded.
Canada reports more than 300 suspected cases of SARS
Authors: D. Spurgeon
Journal: BMJ (2003)

Canadian health officials fear that severe acute respiratory syndrome (SARS) might spread into the wider community, although those working in hospitals treating victims are at highest risk.

Speaking to the Canadian Broadcasting Corporation on 21 April, Dr Jay Keystone of the University of Toronto's Centre of Travel and Tropical Medicine, said: “If we start to …
ABC of colorectal cancer: Innovative treatment for colon cancer
Authors: G A Chung-Faye, D J Kerr
Journal: BMJ (2000)

Despite advances in treatment for colon cancer, the five year survival has not significantly altered over the past decade. Survival could improve in several key areas:

Dietary modifications to reduce the incidence of colon cancer may be difficult to implement (dietary interventional studies have shown this to be the case for cardiovascular disease); the roles of screening, chemotherapy, and radiotherapy have been covered earlier in this series 



Use of non-steroidal anti-inflammatory drugs (NSAID) and relative risk of colorectal cancer



This article will focus on prevention with non-steroidal anti-inflammatory drugs and on new strategies for treating colon cancer.

Evidence strongly suggests a protective effect of non-steroidal anti-inflammatory drugs in colon cancer. Several cohort and case-control studies have consistently shown dose related reductions of colorectal cancer in regular users of these drugs. Furthermore, patients with familial adenomatous polyposis who took the non-steroidal anti-inflammatory sulindac had reductions in the number and size of their polyps. Gene knockout studies in mice suggest that inhibition of the cyclo-oxygenase type 2 pathway by non-steroidal anti-inflammatory drugs may be important in the mechanism of action.



Cell mediated immunity against tumours. Tumour antigens are taken up and processed by antigen presenting cells (APC) and re-presented to class II receptors on T helper cells. This requires a costimulatory signal, B7, which binds to the CD28 ligand, causing T helper cell activation. This leads to secretion of cytokines, which in turn activates cytotoxic lymphocytes to bind to tumour cells via class I receptors and causes tumour lysis



The only randomised controlled trial examining the …
Introduction to the Second International Conference on Scapular Dyskinesis in Shoulder Injury—the ‘Scapular Summit’ Report of 2013
Authors: W Ben Kibler, Aaron D Sciascia
Journal: British Journal of Sports Medicine (2013)

The road has been long but definite progress has been made. I first became aware of the importance of the scapula in shoulder injury in 1984. A young patient with impingement syndrome not responsive to the ‘usual’ treatments was almost immediately relieved of her symptoms when I recognised the altered scapular position and manually stabilised the scapula. We started looking more closely at the scapula and developed a tentative evaluation method. Our first paper was delivered at the 1989 American Orthopaedic Society for Sports Medicine meeting, and the discussion centred on “Does this exist, and does this play any role in shoulder?”

Subsequent investigations and collaborative conferences involving multiple authors showed that scapular dyskinesis does exist, established a clinical definition of scapular dyskinesis and described normal scapular mechanics in shoulder …
COST-EFFECTIVENESS OF PERCUTANEOUS CORONARY INTERVENTION WITH TAXUS STENTS IN PATIENTS WITH MULTIVESSEL CORONARY ARTERY DISEASE COMPARED WITH AORTOCORONARY BYPASS SURGERY 5 YEARS AFTER INTERVENTION
Authors: Marianna Gyoengyoesi, Lisa Krenn, Dietmar Glogar, Gerald Maurer
Journal: Journal of the American College of Cardiology (2012)
Haemodynamic effects of beta blockade in hypertrophic cardiomyopathy using Sectral (acebutolol; M &amp; B 17803A)
Authors: B. S. LEWIS, A. S. MITHA, A. BAKST, K. PURDON, M. S. GOTSMAN
Journal: Cardiovascular Research (1974)

Journal Article Haemodynamic effects of beta blockade in hypertrophic cardiomyopathy using Sectral (acebutolol; M & B 17803A) Get access B. S. LEWIS, B. S. LEWIS From the Cardiac Unit, Wentworth Hospital and the University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar A. S. MITHA, A. S. MITHA From the Cardiac Unit, Wentworth Hospital and the University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar A. BAKST, A. BAKST From the Cardiac Unit, Wentworth Hospital and the University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar K. PURDON, K. PURDON From the Cardiac Unit, Wentworth Hospital and the University of Natal, Durban, South Africa Search for other works by this author on: Oxford Academic PubMed Google Scholar M. S. GOTSMAN M. S. GOTSMAN 1 From the Cardiac Unit, Wentworth Hospital and the University of Natal, Durban, South Africa 1Address for reprints: Professor M. S. Gotsman, Wentworth Hospital, P. B. Jacobs, Natal, South Africa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 2, March 1974, Pages 249–262, https://doi.org/10.1093/cvr/8.2.249 Published: 01 March 1974
The 28th Amendment
Authors: Richard L. Neubauer
Journal: Annals of Internal Medicine (1999)

Letters5 October 1999The 28th AmendmentRichard L. Neubauer, MDRichard L. Neubauer, MDAnchorage, AK 99508 (Neubauer)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-7-199910050-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I was intrigued by Davidoff and Reinecke's editorial (1) proposing a constitutional amendment that states “All citizens and other residents of the United States shall have equal access to basic and essential health care.” I think discussion and possible passage of such an amendment would indeed help to clarify the debate about how to restructure our health care delivery system.I offer a slight modification to the wording of the proposed amendment: “All citizens and other residents of the United States shall have equal access to basic and essential health and legal care.”If we are to ...Reference1. Davidoff F, Reinecke RD. The 28th Amendment [Editorial]. Ann Intern Med. 1999;130:692-4. LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Richard L. Neubauer, MDAffiliations: Anchorage, AK 99508 (Neubauer) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe 28th Amendment Frank Davidoff and Robert D. Reinecke The 28th Amendment Frederick Paola The 28th Amendment Thomas J. Romano The 28th Amendment Ruric Anderson The 28th Amendment Frank Davidoff and Robert D. Reinecke Metrics 5 October 1999Volume 131, Issue 7Page: 542KeywordsHealth care ePublished: 15 August 2000 Issue Published: 5 October 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dermal Deposition of Eosinophil-Granule Major Basic Protein in Atopic Dermatitis
Authors: Kristin M. Leiferman, Steven J. Ackerman, Hugh A. Sampson, Heidi S. Haugen, Pierre Y. Venencie, Gerald J. Gleich
Journal: New England Journal of Medicine (1985)

Although blood eosinophilia is commonly present in atopic dermatitis, accumulation of tissue eosinophils is not prominent. To determine whether eosinophil degranulation occurs in lesions of atopic dermatitis, we analyzed tissues by immunofluorescence for the presence of the eosinophil-granule major basic protein. Twenty biopsy specimens from 18 patients with atopic dermatitis were studied, and all showed major basic protein staining outside eosinophils. In 18 specimens, the staining was fibrillar, was located in the upper half of the dermis, and was similar to the distribution of elastic fibers. Twelve specimens with fibrillar staining also showed major basic protein staining in the form of extracellular granules. One specimen from unaffected skin showed minimal faint, fine, fluorescing fibrils, but there was marked deposition of the protein in affected skin. The fibrillar pattern of major basic protein staining in atopic dermatitis was very similar to that seen in lichenified lesions of untreated onchocerciasis. These results suggest that eosinophils commonly release granule proteins in the dermis and that assessment of eosinophil involvement in disease cannot be based simply on numbers of eosinophils in tissue.
To the Best of Our Knowledge, Which Is Limited at Best
Authors: Samuel Vaisrub
Journal: JAMA (1979)

When on the morning of the new year a local telecaster smilingly announces the name, the hour, and the place of birth of the year's first newborn, we can be reasonably confident that the information is correct. After all, it is based on data obtained from all the area hospitals. Our certainty, however, is not absolute. Occasionally a birth that occurs in an obscure rooming house, an out-of-the-way cabin, or a taxicab remains unreported. The announced firstborn may not be a first after all.  How much greater must our uncertainty be when a medical author reports a first—be it disease, syndrome, or physical sign. The data base for such a claim to priority must of necessity extend to the ends of the globe and the beginnings of medical writing. An appropriately extensive search of the literature is an undertaking that borders on the impossible. The bibliographic sources for such a
Defective renal calcium reabsorption in genetic hypercalciuric rats
Authors: Shuichi Tsuruoka, David A. Bushinsky, George J. Schwartz
Journal: Kidney International (1997)

Idiopathic hypercalciuria is a frequent cause of calcium (Ca) containing kidney stones. We have previously shown that there is increased intestinal Ca absorption in selectively inbred genetic hypercalciuric stone forming (GHS) rats; however, excess Ca excretion persists when the rats are fed a low Ca diet indicating a defect in renal Ca reabsorption and/or increased bone resorption. To determine if GHS rats have a defect in renal Ca reabsorption we performed 14C-inulin clearance studies on parathyroidectomized female GHS and control (Ctl) rats. After three baseline collections, chlorothiazide (CTZ) or furosemide (FUR) was infused and three more collections were obtained. Both GFR and filtered load of Ca did not differ among the groups; however, fractional and absolute excretion (UcaV) of Ca was three times higher in GHS rats. The increased Ca excretion was not diminished by a low Ca diet. Urine flow rate nearly tripled in all rats after either FUR or CTZ. After CTZ, UcaV was decreased to a greater extent in GHS compared to Ctl rats. After FUR, UcaV was increased to a greater extent in Ctl rats compared to GHS rats. These data indicate that GHS rats have a defect in renal Ca reabsorption, in addition to increased intestinal Ca absorption. The effect of CTZ was greater, and that of FUR was smaller, in GHS compared with Ctl rats, suggesting that the defect in renal Ca handling might be at the level of the thick ascending limb.
A Shared Destiny: Community Effects of Uninsurance
Authors: P. J. Cunningham
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Scintigraphic Evaluation of a Patient With Lung Cavitations
Authors: DAVY ZISMAN, RUTH HARDOFF, HAIM BITTERMAN
Journal: Clinical Nuclear Medicine (1994)

Primary nonHodgkin's lymphoma (NHL) of the lung is an uncommon neoplasm and accounts for only 0.34–0.4% of all NHL. The most common type is the low grade—small lymphocytic lymphoma (50–70%). More than half of the patients are asymptomatic at the time of diagnosis when a mass is discovered on a routine chest x-ray. Pulmonary involvement in patients with lung lymphoma poses considerable diagnostic and management problems. Both the altered immune status and the effects of the combined chemo-radio therapy on the lung may cause a wide range of pulmonary complications such as infection, drug induced pneumonitis, and hemorrhage. The clinical presentation and imaging in lung lymphoma may not always be helpful in making the diagnosis. A patient with high-grade primary NHL of the lung that masked as a prolonged febrile disease with multiple lung cavities was initially thought to be a lung abscess. The intense Ga-67 uptake could not differentiate between an infectious and neoplastic process. It's disappearance after chemotherapy established its origin to be neoplastic. Ga-67 could therefore serve as an adjunct for staging as well as the follow-up of this rare condition.
LOCALIZATION OF IMMUNOLOGICAL COMPLEXES FIXING ß1C (C3) IN GERMINAL CENTERS OF LYMPH NODES
Authors: K. J. Gajl-Peczalska, A. J. Fish, H. J. Meuwissen, D. Frommel, R. A. Good
Journal: The Journal of Experimental Medicine (1969)

28 human and 60 experimentally stimulated rabbit lymph nodes were studied by means of light microscopy and immunofluorescence. 21 of the 28 human lymph nodes showed well-developed germinal centers. IgM, IgG, and the ß1C component of complement were found in the same distribution within germinal centers when examined in serial cryostat sections. 36 rabbits were stimulated with Brucella antigen, and 24 rabbits with BSA. A strikingly consistent correlation between distribution and appearance of specific staining for rabbit ß1C, IgM, and IgG was observed; when lymph nodes were stimulated with BSA, antigen and specific antibody were present. Treatment of unfixed sections with citrate-buffered saline at low pH resulted in complete elution of immunoglobulins, ß1C, and BSA from rabbit germinal centers, and in marked diminution of IgG and IgM in human germinal centers, while at the same time plasma cells remained strongly fluorescent. Specific selective fixation of heterologous (human) complement in rabbit germinal centers positive for ß1C, IgG, IgM, and BSA was also obtained. These data present strong evidence for the existence within germinal centers of antigen-antibody complexes which fix at least the ß1C component of complement in vivo. The possibility of complete elution of immunoglobulins from rabbit germinal centers can be taken as evidence that, at least for 20 days after primary and secondary stimulation, a major component of the immunoglobulins present in germinal centers is not produced locally but accumulates at the surface of cells.
Dislocation of Patella and its Relation to Chondromalacia Patellae
Authors: H. H. Langston
Journal: BMJ (1958)

The purpose of this paper is to put forward a twofold suggestion.Firstly, that traumatic outward subluxation of the patella, due to rotational strains of the knee, is a more common injury than is often thought; and, secondly, that such subluxations, if recurrent, especially in the young adult male, are a common cause of the development of chondromalacia patellae.
Effect of Environmental Tobacco Smoke on Levels of Urinary Hormone Markers
Authors: Changzhong Chen, Xiaobin Wang, Lihua Wang, Fan Yang, Genfu Tang, Houxun Xing, Louise Ryan, Bill Lasley, James W. Overstreet, Joseph B. Stanford, Xiping Xu
Journal: Environmental Health Perspectives (2005)

Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a +/-10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (beta = -0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (beta = -0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.