tbuckley/cabot-search huggingface dataset:
Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study)
Authors: Marjatta Leirisalo-Repo, Hannu Kautiainen, Leena Laasonen, Markku Korpela, Markku J Kauppi, Oili Kaipiainen-Seppänen, Riitta Luosujärvi, Reijo Luukkainen, Anna Karjalainen, Harri Blåfield, Toini Uutela, Kirsti Ilva, Heikki A Julkunen, Leena Paimela, Kari Puolakka, Eeva Moilanen, Pekka J Hannonen, Timo Möttönen
Journal: Annals of the Rheumatic Diseases (2012)

Objective Early treatment of patients with rheumatoid arthritis (RA) with combination treatment starting with methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (FIN-RACo strategy) is superior to monotherapy. A study was undertaken to determine whether infliximab (INFL) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome. Methods 99 patients with early untreated active RA were enrolled in an investigator-initiated, randomised, double-blind, multicentre, parallel-group trial. Primary outcomes were remission and radiological changes at 2 years. All patients started with FIN-RACo. In addition, they were randomised to receive INFL or placebo (Pla) from weeks 4 to 26. Results At 24 months, 66% and 53%, respectively, of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology (ACR) criteria (p=0.19), 26% and 10% were in sustained modified ACR remission (p=0.042) and 82% in both groups were in remission by 28-joint disease activity score (not significant). Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4, respectively (p=0.0058). Conclusions Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen. Adding INFL for the first 6 months delays radiological progression.
Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: A prospective controlled study
Authors: Maria Dalamaga, Evangelia Papadavid, Georgios Basios, Vassilios Vaggopoulos, Dimitrios Rigopoulos, Dimitrios Kassanos, Eftihios Trakakis
Journal: Journal of the American Academy of Dermatology (2013)
Role of Parathyroid Hormone–Related Protein in Tubulointerstitial Apoptosis and Fibrosis after Folic Acid–Induced Nephrotoxicity
Authors: Arantxa Ortega, David Rámila, Juan Antonio Ardura, Vanesa Esteban, Marta Ruiz-Ortega, Antonio Barat, Rosa Gazapo, Ricardo J. Bosch, Pedro Esbrit
Journal: Journal of the American Society of Nephrology (2006)

Parathyroid hormone–related protein (PTHrP) is shortly upregulated in acute renal injury, but its pathophysiologic role is unclear. Investigated was whether PTHrP might act as a profibrogenic factor in mice that do or do not overexpress PTHrP in the proximal tubule after folic acid (FA) nephrotoxicity, a model of acute renal damage followed by partial regeneration and patchy tubulointerstitial fibrosis. It was found that constitutive PTHrP overexpression in these animals conveyed a significant increase in tubulointerstitial fibrosis, associated with both fibroblast activation (as α-smooth muscle actin staining) and macrophage influx, compared with control littermates at 2 to 3 wk after FA damage. Cell proliferation and survival was higher (P < 0.01) in the renal interstitium of PTHrP-overexpressing mice than in control littermates within this period after injury. Moreover, the former mice had a constitutive Bcl-XL protein overexpression. In vitro studies in renal tubulointerstitial and fibroblastic cells strongly suggest that PTHrP (1-36) (100 nM) reduced FA-induced apoptosis through a dual mechanism involving Bcl-XL upregulation and Akt and Bad phosphorylation. PTHrP (1-36) also stimulated monocyte chemoattractant protein-1 expression in tubuloepithelial cells, as well as type-1 procollagen gene expression and fibronectin (mRNA levels and protein secretion) in these cells and renal fibroblastic cells. Our findings indicate that this peptide, by interaction with the PTH1 receptor, can increase tubulointerstitial cell survival and seems to act as a proinflammatory and profibrogenic factor in the FA-damaged kidney.
Intensive Glucose Control in Elderly Adults
Authors: Rodney A. Hayward, Timothy P. Hofer, Sandeep Vijan
Journal: JAMA (2007)

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
INDUCTION OF MACROPHAGE PLASMINOGEN ACTIVATOR BY ENDOTOXIN STIMULATION AND PHAGOCYTOSIS
Authors: Saimon Gordon, Ay C. Unkeless, Z. A. Cohn
Journal: The Journal of Experimental Medicine (1974)

The injection of thioglycollate medium into the peritoneal cavity of the mouse induces high levels of macrophage fibrinolytic activity due to the production and secretion of a plasminogen activator, a trypsinlike serine protease, which is absent in unstimulated macrophages. Intraperitoneal injection of endotoxin or mineral oil can stimulate only a fraction (&amp;lt;10%) of the fibrinolytic activity of thioglycollate cells, similar to the partial stimulation (&amp;lt;10%) seen 1–2 days after phagocytosis of latex or SRBC by unstimulated macrophages. The endotoxin-stimulated macrophages contain and release relatively low levels of plasminogen activator, but these primed cells can be triggered to produce and secrete high levels of enzyme, by phagocytosis of latex. Under conditions where the plasminogen activator is induced and secreted, there are no effects on the production and/or release of lysozyme or intracellular acid hydrolases, Discovery of a two-stage procedure for inducing macrophage plasminogen activator made it possible to study the role of cell priming and phagocytosis separately. Endotoxin was a more effective priming agent, weight for weight, than lipid A:BSA complex. Secretion of the plasminogen activator was induced only by thioglycollate, or endotoxin and latex. In situ fibrinolysis was induced by these agents and mineral oil, BCG, and fetal calf serum, in decreasing order of effectiveness. Phagocytosis of latex in all cases except thioglycollate stimulation, increased fibrinolytic activity from three- to sixfold. Latex and a variety of other particles such as M. lysodeikticus, aggregated γ-globulin and immune complexes showed dose-dependent stimulation of fibrinolysis by endotoxin-primed macrophages. Although the initial phagocytic trigger was not specific for the substance employed, the ability to induce a sustained response depended on the persistence of the phagocytized particle within the cell. Fibrinolysis and secretion of plasminogen activator continued at high levels for at least 9 days after uptake of latex, a nondigestible particle, whereas plasminogen activator was secreted only transiently after ingestion of rapidly digested M. lysodeikticus. The induction of plasminogen activator secretion provides a mechanism by which the activated macrophage can exert a selective effect on its extracellular environment.
Incidence of non-melanoma skin cancer in West Glamorgan, South Wales
Authors: D.LLOYD ROBERTS
Journal: British Journal of Dermatology (1990)

Journal Article Incidence of non‐melanoma skin cancer in West Glamorgan, South Wales Get access D.LLOYD ROBERTS D.LLOYD ROBERTS Singleton Hospital, Swansea, W.Glamorgan, U.K. Dr Dafydd Lloyd Roberts, Consultant Dermatologist, Singleton Hospital, Swansea, SA2 8QA, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue 3, 1 March 1990, Pages 399–403, https://doi.org/10.1111/j.1365-2133.1990.tb08289.x Published: 01 March 1990
PTP1B Is an Androgen Receptor–Regulated Phosphatase That Promotes the Progression of Prostate Cancer
Authors: Laurent Lessard, David P. Labbé, Geneviève Deblois, Louis R. Bégin, Serge Hardy, Anne-Marie Mes-Masson, Fred Saad, Lloyd C. Trotman, Vincent Giguère, Michel L. Tremblay
Journal: Cancer Research (2012)

The androgen receptor (AR) signaling axis plays a key role in the pathogenesis of prostate cancer. In this study, we found that the protein tyrosine phosphatase PTP1B, a well-established regulator of metabolic signaling, was induced after androgen stimulation of AR-expressing prostate cancer cells. PTP1B induction by androgen occurred at the mRNA and protein levels to increase PTP1B activity. High-resolution chromosome mapping revealed AR recruitment to two response elements within the first intron of the PTP1B encoding gene PTPN1, correlating with an AR-mediated increase in RNA polymerase II recruitment to the PTPN1 transcriptional start site. We found that PTPN1 and AR genes were coamplified in metastatic tumors and that PTPN1 amplification was associated with a subset of high-risk primary tumors. Functionally, PTP1B depletion delayed the growth of androgen-dependent human prostate tumors and impaired androgen-induced cell migration and invasion in vitro. However, PTP1B was also required for optimal cell migration of androgen-independent cells. Collectively, our results established the AR as a transcriptional regulator of PTPN1 transcription and implicated PTP1B in a tumor-promoting role in prostate cancer. Our findings support the preclinical testing of PTP1B inhibitors for prostate cancer treatment.
An Interleukin 5 Mutant Distinguishes between Two Functional Responses in Human Eosinophils
Authors: Murray McKinnon, Kevin Page, Iain J. Uings, Martyn Banks, Dilniya Fattah, Amanda E.I. Proudfoot, Pierre Graber, Christian Arod, Richard Fish, Timothy N.C. Wells, Roberto Solari
Journal: The Journal of Experimental Medicine (1997)

Interleukin 5 (IL-5) is the key cytokine involved in regulating the production and many of the specialized functions of mature eosinophils including priming, adhesion, and survival. We have generated a point mutant of human IL-5, IL-5 (E12K), which is devoid of agonist activity in both a TF-1 cell proliferation assay and a human eosinophil adhesion assay. However, IL-5 (E12K) is a potent and specific antagonist of both these IL-5-dependent functional responses. In both receptor binding and cross-linking studies the wild-type and IL-5 (E12K) mutant exhibit virtually identical properties. This mutant protein was unable to stimulate tyrosine phosphorylation in human eosinophils, and blocked the phosphorylation stimulated by IL-5. In contrast, IL-5 (E12K) is a full agonist in a human eosinophil survival assay, although with reduced potency compared to the wild-type protein. This IL-5 mutant enables us to clearly distinguish between two IL-5-dependent functional responses and reveals distinct mechanisms of receptor/cellular activation.
THE IODOFORM TREATMENT OF TUBERCULOUS DISEASE
Authors: M. Connon
Journal: BMJ (1903)

In Column A are tlle numiiber of red cells per c.mrm. as found by countnng in the ordinary way on a Zeiss slide.A dilution of I ill 200 in the umethyl violet diluting fluid was used for this purpose, eight large squares each consisting of sixteen siimall squares being counted.For column B 5 c.rnm. of time first dilution were takeni and mixeS with 495 c.mm. of the eosin solution.This gives a final dilution of I in 20,000.Yrom this dilution drops were blowln on to slides fromii one of the specially graduated 5 c.mmn.pipettes.Tllese were dried and mounted in -Canada balsam.One slide was selected and counted.Since the dilution wvas I in 20,0o0 and the total red cells in 5 c.amn. were counted, the total count multiplied by 20,000.5 ==4,000 gives tlle number of red cells per c.mm.The numbers so obtained are given in coluiimn 15.
Active ulcerative colitis is associated with downregulation of the TH1, TH2 and TH17 cytokine response and elevated IL-8 levels in mucosal biopsies
Authors: D. S. Pearl, K. Shah, J. Brown, J. K. Shute, T. M. Trebble
Journal: Gut (2011)

<h3>Introduction</h3> Ulcerative colitis (UC) is a chronic inflammatory condition of unconfirmed aetiology. Microscopic examination of inflamed biopsies is characterised by an acute and chronic inflammatory cell infiltrate. There is conflicting evidence from experimental studies on the relative roles of TNFα, IL-8 and cytokines released by Th1, Th2 and Th17 lymphocytes in UC. This may be further complicated by interindividual variation in cytokine release due to genetic polymorphism. However, current therapy in inflammatory bowel disease includes cytokine targeted interventions. The authors compared cytokine profiles of inflamed and non-inflamed mucosa in UC and age-sex matched controls. <h3>Methods</h3> Ethical approval was obtained. Patients were prospectively recruited from outpatients9 clinics. Mucosal biopsies at flexible sigmoidoscopy (FS) were taken from active UC patients within inflamed (active) and endoscopically normal proximal mucosa (internal control), and age-sex matched (external) controls undergoing FS. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8 and IFNγ were carried out using commercially available assays on tissue homogenates prepared with protease inhibitors, corrected for total protein. Statistical comparison was by Wilcoxon signed rank pair analysis for non-parametric data. <h3>Results</h3> 69 active UC patients (54 paired normal/inflamed mucosa) and 69 controls were compared. No biologically significant differences were noted between normal tissue from colitis patients and external control mucosa. Cytokine measurements in inflamed mucosa compared with uninflamed mucosa from the same patients demonstrated significant reductions in IL-4 (p&lt;0.005), IFNγ (p&lt;0.002) and IL-17A. (p&lt;0.002), whereas IL-8 (p&lt;0.0005) was significantly increased. Similarly, IFNγ was decreased (p&lt;0.02) and IL-8 increased (p&lt;0.0001) in inflamed mucosa compared with external control tissue; TNFα was not significantly different in inflamed compared with control mucosa. <h3>Conclusion</h3> This findings suggest that cytokine release within normal mucosa in UC patients is not significantly different from matched controls; however, in inflamed mucosa, cytokines released by Th1, Th2 and Th17 lymphocytes are reduced and TNFα is unchanged. In contrast, IL-8 (a potent neutrophil chemoattractant) is elevated. These findings suggest that the immunopathogenesis underlying the inflammatory response in UC may be reflective of an alternative to a Th1, Th2 and Th17 driven chronic inflammatory system and may involve an IL-8 mediated leukocytic infiltrate.
Oral contraceptives do not appear to affect cystic fibrosis disease severity
Authors: Natalie G. Kernan, Eric W.F.W. Alton, Paul Cullinan, Uta Griesenbach, Diana Bilton
Journal: European Respiratory Journal (2012)

Several studies suggest that sex may affect cystic fibrosis (CF) disease severity, with females with CF being more severely affected. In this context, it has been suggested that sex hormones may influence the CF phenotype. A large proportion of females with CF regularly use oral contraceptives (OCs), but the effect of their use on disease severity is unclear. Here, we retrospectively assessed the effects of OCs on clinical outcomes in females with CF. Data from 681 females were available, of whom 42% had taken OCs for varying periods of time. We first performed an inter-patient analysis comparing annual change in % predicted forced expiratory volume in 1 s, body mass index and total days of intravenous antibiotic use over a 5-yr study period in 57 females exposed to and 57 females not exposed to OCs. There were no differences between the two groups. We next performed an intra-patient analysis of the same outcomes over a 3-yr period of OC exposure and a 3-yr period of no OC exposure in the same patient (exposure followed by non-exposure, n=27; non-exposure followed by exposure, n=23), but again did not detect any differences in any of the clinical outcomes. Our data suggests that the use of OCs does not affect CF disease severity.
A novel approach to manage skin toxicity caused by therapeutic agents targeting epidermal growth factor receptor
Authors: A. Campanati, R. Berardi, A. Onofri, C. Pierantoni, I. Conte, K. Giuliodori, E. Molinelli, F. Marcucci, S. Cascinu, A. Offidani
Journal: Annals of Oncology (2012)
Influence of olsalazine on gastrointestinal transit in ulcerative colitis.
Authors: S S Rao, N W Read, C D Holdsworth
Journal: Gut (1987)

The effect of olsalazine on stool output and the transit of a solid radiolabelled meal through the stomach, small intestine and colon was studied in six patients with ulcerative colitis intolerant of sulphasalazine. Olsalazine 250 mg four times daily significantly accelerated gastric emptying (mean +/- SD; 45.3 +/- 24.2 min v 67.3 +/- 33.1 min, p less than 0.05), mouth to caecum transit time (242 +/- 41 min v 325 +/- 33 min, p less than 0.02) and whole gut transit time (60.5 +/- 26 h v 37.8 +/- 17.8 h, p less than 0.05). No significant changes were seen in mean daily stool weight (215 +/- 41 g v 162 +/- 62 g) and mean daily stool frequency (2.2 +/- 0.6 v 2.4 +/- 1.8). None of these patients developed diarrhoea, but acceleration of gastric and intestinal transit may be responsible for the diarrhoea reported in some patients taking this drug.
Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.
Authors: T Naveh-Many, J Silver
Journal: Journal of Clinical Investigation (1990)

In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium.
Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer: analysis of 505 randomized patients
Authors: R. Arriagada, T. Le Chevalier, A. Rivière, P. Chomy, I. Monnet, E. Bardet, J.A. Santos-Miranda, C. Le Péchoux, M. Tarayre, S. Benhamou, A. Laplanche
Journal: Annals of Oncology (2002)
ICOS Coreceptor Signaling Inactivates the Transcription Factor FOXO1 to Promote Tfh Cell Differentiation
Authors: Erica L. Stone, Marion Pepper, Carol D. Katayama, Yann M. Kerdiles, Chen-Yen Lai, Elizabeth Emslie, Yin C. Lin, Edward Yang, Ananda W. Goldrath, Ming O. Li, Doreen A. Cantrell, Stephen M. Hedrick
Journal: Immunity (2015)

Highlights•ICOS signaling transiently inactivates FOXO1 to generate Tfh cells•FOXO1 regulates a Tfh cell gene program exemplified by negative regulation of Bcl6•Enforced nuclear localization of FOXO1 prevents Tfh cell differentiation•FOXO1 promotes final GC-Tfh cell differentiationSummaryT follicular helper (Tfh) cells are essential in the induction of high-affinity, class-switched antibodies. The differentiation of Tfh cells is a multi-step process that depends upon the co-receptor ICOS and the activation of phosphoinositide-3 kinase leading to the expression of key Tfh cell genes. We report that ICOS signaling inactivates the transcription factor FOXO1, and a Foxo1 genetic deletion allowed for generation of Tfh cells with reduced dependence on ICOS ligand. Conversely, enforced nuclear localization of FOXO1 inhibited Tfh cell development even though ICOS was overexpressed. FOXO1 regulated Tfh cell differentiation through a broad program of gene expression exemplified by its negative regulation of Bcl6. Final differentiation to germinal center Tfh cells (GC-Tfh) was instead FOXO1 dependent as the Foxo1−/− GC-Tfh cell population was substantially reduced. We propose that ICOS signaling transiently inactivates FOXO1 to initiate a Tfh cell contingency that is completed in a FOXO1-dependent manner.
Capecitabine and vinorelbine in elderly patients (≥65 years) with metastatic breast cancer: a phase I trial (SAKK 25/99)
Authors: D. Hess, B. Thürlimann, O. Pagani, S. Aebi, D. Rauch, P. Ballabeni, B. Rufener, M. Castiglione-Gertsch, A. Goldhirsch
Journal: Annals of Oncology (2004)