tbuckley/cabot-search huggingface dataset:
Predictors of radiographic progression in the ESPOIR cohort: the season of first symptoms may influence the short-term outcome in early arthritis
Authors: G. Mouterde, C. Lukas, I. Logeart, R. M. Flipo, N. Rincheval, J. P. Daures, B. Combe
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To determine predictors of short-term radiographic progression in an inception cohort of patients with early arthritis. <h3>Methods</h3> Patients presenting with synovitis of at least two joints for 6 weeks to 6 months were included in the Etude et Suivi des POlyarthrites Indifferenciées Récentes (ESPOIR) cohort. Univariate analysis was used to determine the relationship between baseline variables and radiographic outcome (assessed by the modified total Sharp score (mTSS)) after 6 and 12 months. Stepwise multiple logistic regression was used to select independent predictive factors. The sensitivity and specificity of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) at baseline in discriminating between erosive and non-erosive disease were determined by receiver operating characteristic (ROC) curves. <h3>Results</h3> From data available for 736 patients, radiographic progression at 6 months was independently predicted by baseline ACPA, human leucocyte antigen (HLA)-DRB1*01 and/or 04 genes, erythrocyte sedimentation rate and mTSS. Interestingly, the season of onset of the first symptoms was associated with the severity of early arthritis (OR 1.66, 95% CI 1.07 to 2.59, in winter and spring vs summer and autumn). Univariate analysis revealed similar results for season at 12 months (OR 1.68, 95% CI 1.20 to 2.37). The peak of the ROC curves for radiographic outcome occurred with ACPA and RF values similar to the cut-offs provided by manufacturers. <h3>Conclusion</h3> The authors found the onset of arthritis symptoms during winter or spring associated with greater radiographic progression at 6 months for patients with early arthritis. These data could reinforce the role of environmental factors in the development and outcome of rheumatoid arthritis.
A Role for Peroxisome Proliferator-Activated Receptor γ Coactivator-1 in the Control of Mitochondrial Dynamics During Postnatal Cardiac Growth
Authors: Ola J. Martin, Ling Lai, Mangala M. Soundarapandian, Teresa C. Leone, Antonio Zorzano, Mark P. Keller, Alan D. Attie, Deborah M. Muoio, Daniel P. Kelly
Journal: Circulation Research (2013)

Increasing evidence has shown that proper control of mitochondrial dynamics (fusion and fission) is required for high-capacity ATP production in the heart. Transcriptional coactivators, peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) α and PGC-1β, have been shown to regulate mitochondrial biogenesis in the heart at the time of birth. The function of PGC-1 coactivators in the heart after birth has been incompletely understood.Our aim was to assess the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts in mice.Conditional gene targeting was used in mice to explore the role of PGC-1 coactivators during postnatal cardiac development and in adult hearts. Marked mitochondrial structural derangements were observed in hearts of PGC-1α/β-deficient mice during postnatal growth, including fragmentation and elongation, associated with the development of a lethal cardiomyopathy. The expression of genes involved in mitochondrial fusion (Mfn1, Opa1) and fission (Drp1, Fis1) was altered in the hearts of PGC-1α/β-deficient mice. PGC-lα was shown to directly regulate Mfn1 gene transcription by coactivating the estrogen-related receptor α on a conserved DNA element. Surprisingly, PGC-1α/β deficiency in the adult heart did not result in evidence of abnormal mitochondrial dynamics or heart failure. However, transcriptional profiling demonstrated that PGC-1 coactivators are required for high-level expression of nuclear- and mitochondrial-encoded genes involved in mitochondrial dynamics and energy transduction in the adult heart.These results reveal distinct developmental stage-specific programs involved in cardiac mitochondrial dynamics.
Effect of Potassium Deficiency on the Reabsorption of Bicarbonate in the Proximal Tubule of the Rat Kidney*
Authors: Floyd C. Rector, H. Allan Bloomer, Donald W. Seldin
Journal: Journal of Clinical Investigation (1964)

Potassium deficiency accelerates the secretion of HI ions by the kidney; in consequence the net excretion of acid (ammonia and titratable acid-bicarbonate) into the urine and the capacity to reabsorb filtered HCO3are increased (1-7).Although the precise mechanism involved has not been identified, Berliner, Kennedy, and Orloff (8), on the basis of the demonstrated reciprocal re- lationship between H4 and K+ secretion, proposed that these ions compete for a common secretory pathway in the distal nephron.Consequently, K+ depletion, by lowering the concentration of K+ at the competitive secretory site, would facilitate H+ secretion and increase the capacity of the distal tubule to reabsorb HCO3-(9).Certain observations, however, are difficult to reconcile with the theory of competitive inhibition.Rector, Buttram, and Seldin (10) found that the inhibitory effects of Ki administration on HCO3- reabsorption could not be overcome by raising in- tracellular H4 concentration by respiratory acido- sis.This observation, which is not consistent with the theory of competitive inhibition between H+ and K+, suggests that K4 might reduce Hi secre- tion by either noncompetitive inhibition or by alka- linizing the renal tubular cells.If alterations of intracellular K+ were capable of changing the pH of renal tubular cells, two consequences might fol- low: first, the inverse relationship between H+ and
Minimal Changes of Serum Creatinine Predict Prognosis in Patients after Cardiothoracic Surgery
Authors: Andrea Lassnigg, Daniel Schmidlin, Mohamed Mouhieddine, Lucas M. Bachmann, Wilfred Druml, Peter Bauer, Michael Hiesmayr
Journal: Journal of the American Society of Nephrology (2004)

Acute renal failure increases risk of death after cardiac surgery. However, it is not known whether more subtle changes in renal function might have an impact on outcome. Thus, the association between small serum creatinine changes after surgery and mortality, independent of other established perioperative risk indicators, was analyzed. In a prospective cohort study in 4118 patients who underwent cardiac and thoracic aortic surgery, the effect of changes in serum creatinine within 48 h postoperatively on 30-d mortality was analyzed. Cox regression was used to correct for various established demographic preoperative risk indicators, intraoperative parameters, and postoperative complications. In the 2441 patients in whom serum creatinine decreased, early mortality was 2.6% in contrast to 8.9% in patients with increased postoperative serum creatinine values. Patients with large decreases (DeltaCrea <-0.3 mg/dl) showed a progressively increasing 30-d mortality (16 of 199 [8%]). Mortality was lowest (47 of 2195 [2.1%]) in patients in whom serum creatinine decreased to a maximum of -0.3 mg/dl; mortality increased to 6% in patients in whom serum creatinine remained unchanged or increased up to 0.5 mg/dl. Mortality (65 of 200 [32.5%]) was highest in patients in whom creatinine increased > or =0.5 mg/dl. For all groups, increases in mortality remained significant in multivariate analyses, including postoperative renal replacement therapy. After cardiac and thoracic aortic surgery, 30-d mortality was lowest in patients with a slight postoperative decrease in serum creatinine. Any even minimal increase or profound decrease of serum creatinine was associated with a substantial decrease in survival.
A controlled study of ultraviolet A sunbed treatment of psoriasis
Authors: R.J. Turner, D. Walshaw, B.L. Diffey, P.M. Farr
Journal: British Journal of Dermatology (2000)

Background Ultraviolet (UV) A sunbeds are widely used by patients with psoriasis in an attempt to treat their skin disease. However, there is little evidence that UVA therapy improves psoriasis, and the long‐term risks of sunbed exposure are not known. Objectives To perform a randomized, placebo‐controlled study of UVA sunbed therapy for psoriasis. Methods A sunbed and canopy unit was modified to allow UVA exposure on one side of the body (front and back), and ‘placebo’ visible light exposure on the other side of the body. We treated 38 patients with psoriasis, giving 12 exposures over a period of 4 weeks. Assessment was made using a modified Psoriasis Area and Severity Index (PASI) score, individual plaque assessment and patient questionnaire. Results In 17 patients (47%) the PASI score showed a greater reduction on the UVA side compared with placebo, in 11 patients (31%) no difference was recorded between the two sides, and in eight (22%) the improvement was greater on the placebo‐treated side. Overall, the median pretreatment half‐body modified PASI score was 4·4 units, reducing to 3·9 units on the UVA‐treated side and 4·2 units on the placebo‐treated side (P = 0·044 for difference in response). Breakdown of the plaque score into the individual components of erythema, scale and thickness revealed significant improvement only with the score for erythema. Although the degree of improvement was small, 64% of patients felt that the response was sufficiently good that they would use a sunbed again to treat their psoriasis. Conclusions Our results show that a short course of sunbed treatment does improve psoriasis in some patients, but that the degree of improvement is small.
Effect of excising Freund's adjuvant granuloma on subsequent development of experimental allergic arthritis.
Authors: D Hirschowitz, A Fox, L E Glynn
Journal: Annals of the Rheumatic Diseases (1977)

Rabbits were immunized with antigen in Freund9s complete adjuvant. Several weeks later the granuloma which developed was excised one day before joint challenge with antigen. The subsequent development of experimental allergic arthritis (EAA) was not affected, which argues against the chronicity of the disease being maintained by continuous recruitment of mycobacterial debris to EAA joints.
Longitudinal Population-Based Twin Study of Retrospectively Reported Premenstrual Symptoms and Lifetime Major Depression
Authors: Kenneth S. Kendler, Laura M. Karkowski, Linda A. Corey, Michael C. Neale
Journal: American Journal of Psychiatry (1998)

Objective: While family and twin studies suggest that retrospectively reported premenstrual symptoms are heritable, these studies have not accounted for the unreliability of such measures. In addition, we know little about the relationship of the familial risk factors for premenstrual symptoms and major depression. Method: Lifetime major depression and premenstrual-related tiredness, sadness, and irritability were assessed twice over 6 years in 1,312 menstruating female twins ascertained from a population-based twin register. A twin-measurement model—which permits estimation of the etiologic roles of genetic and environmental factors with correction for errors of measurement or short-term temporal fluctuations—was applied to these data.Results: A single premenstrual symptom factor was found that was moderately stable over time. The best-fitting twin-measurement model estimated the heritability of the stable component of premenstrual symptoms at 56% and showed no impact of family-environmental factors. A bivariate twin-measurement model estimated that the genetic and environmental risk factors for lifetime major depression contributed only modestly to the etiology of premenstrual syndrome. No evidence was found for significant biases in the twin method.Conclusions: Retrospectively reported premenstrual-related symptoms of depression and anxiety are moderately stable over time and, when correction is made for this level of stability, substantially heritable. The genetic and environmental risk factors for these premenstrual symptoms and lifetime major depression are not closely related. Am J Psychiatry 1998; 155: 1234-1240
Autonomic Effects of Controlled Fine Particulate Exposure in Young Healthy Adults: Effect Modification by Ozone
Authors: Asghar A. Fakhri, Ljubomir M. Ilic, Gregory A. Wellenius, Bruce Urch, Frances Silverman, Diane R. Gold, Murray A. Mittleman
Journal: Environmental Health Perspectives (2009)

Human controlled-exposure studies have assessed the impact of ambient fine particulate matter on cardiac autonomic function measured by heart rate variability (HRV), but whether these effects are modified by concomitant ozone exposure remains unknown.In this study we assessed the impact of O(3) and particulate matter exposure on HRV in humans.In a crossover design, 50 subjects (19-48 years of age) were randomized to 2-hr controlled exposures to filtered air (FA), concentrated ambient particles (CAPs), O(3), or combined CAPs and ozone (CAPs + O(3)). The primary end point was change in HRV between the start and end of exposure. Secondary analyses included blood pressure (BP) responses, and effect modification by asthmatic status.Achieved mean CAPs and O(3) exposure concentrations were 121.6 +/- 48.0 microg/m(3) and 113.9 +/- 6.6 ppb, respectively. In a categorical analysis, exposure had no consistent effect on HRV indices. However, the dose-response relationship between CAPs mass concentration and HRV indices seemed to vary depending on the presence of O(3). This heterogeneity was statistically significant for the low-frequency component of HRV (p = 0.02) and approached significance for the high-frequency component and time-domain measures of HRV. Exposure to CAPs + O(3) increased diastolic BP by 2.0 mmHg (SE, 1.2; p = 0.02). No other statistically significant changes in BP were observed. Asthmatic status did not modify these effects.The potentiation by O(3) of CAPs effects on diastolic BP and possibly HRV is of small magnitude in young adults. Further studies are needed to assess potential effects in more vulnerable populations.
hVps37A Status Affects Prognosis and Cetuximab Sensitivity in Ovarian Cancer
Authors: Michael Wittinger, Petr Vanhara, Ahmed El-Gazzar, Bettina Savarese-Brenner, Dietmar Pils, Mariam Anees, Thomas W. Grunt, Maria Sibilia, Martin Holcmann, Reinhard Horvat, Michael Schemper, Robert Zeillinger, Christian Schöfer, Helmut Dolznig, Peter Horak, Michael Krainer
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Although prognostic and predictive factors in ovarian cancer have been extensively studied for decades, only few have been identified and introduced to clinical practice. Here, we evaluate hVps37A (HCRP1) as a possible novel predictive marker for ovarian cancer. hVps37A was originally described as a member of the membrane-trafficking ESCRT-I complex mediating the internalization and degradation of ubiquitinated membrane receptors. Experimental Design: We analyzed an ovarian cancer tissue microarray for HCRP1, EGFR, and HER2 expression. We used a tetracycline inducible ovarian cancer cell culture model to show the effects of hVps37A knockdown in vitro and in vivo. In addition, we studied the effects of epidermal growth factor receptor (EGFR) inhibitors cetuximab and lapatinib on ovarian cancer cells under conditions of hVps37A knockdown. Results: We find that hVps37A is significantly downregulated in ovarian cancer and modifies the prognostic value of EGFR and HER2 expression. In addition, hVps37A downregulation in ovarian cancer cells leads to cytoplasmic pEGFR retention and hyperactivation of downstream pathways and is associated with enhanced xenograft growth in nude mice and invasion of the collagen matrix. Furthermore, due to subsequent sustained Akt- and MAPK-pathway activation, hVps37A-deficient cells become irresponsive to inhibition by the therapeutic antibody cetuximab. Conclusion: We propose that hVps37A status could become a novel prognostic and therapeutic marker for EGFR or HER2 driven tumors. Clin Cancer Res; 17(24); 7816–27. ©2011 AACR.
Mammary Tumor Induction in Transgenic Mice Expressing an RNA-Binding Protein
Authors: Charles R. Tessier, Glenn A. Doyle, Brad A. Clark, Henry C. Pitot, Jeff Ross
Journal: Cancer Research (2004)

We have analyzed mammary tumors arising in transgenic mice expressing a novel, multifunctional RNA-binding protein. The protein, which we call the c-myc mRNA coding region instability determinant binding protein (CRD-BP), binds to c-myc, insulin-like growth factor II, and beta-actin mRNAs, and to H19 RNA. Depending on the RNA substrate, the CRD-BP affects RNA localization, translation, or stability. CRD-BP levels are high during fetal development but low or undetectable in normal adult tissues. The CRD-BP is linked to tumorigenesis, because its expression is reactivated in some adult human breast, colon, and lung tumors. These data suggest the CRD-BP is a proto-oncogene. To test this idea, the CRD-BP was expressed from the whey acidic protein (WAP) promoter in mammary epithelial cells of adult transgenic mice. The incidence of mammary tumors was 95% and 60% in two lines of WAP-CRD-BP mice with high and low relative CRD-BP expression, respectively. Some of the tumors metastasized. Nontransgenic mice did not develop mammary tumors. H19 RNA and insulin-like growth factor II mRNA were up-regulated significantly in non-neoplastic WAP-CRD-BP mammary tissue. WAP-CRD-BP mice are a novel model for mammary neoplasia and might provide insights into human breast cancer biology.
Towards a re‐definition of ‘cardiac hypertrophy’ through a rational characterization of left ventricular phenotypes: a position paper of the Working Group ‘Myocardial Function’ of the ESC
Authors: Ralph Knöll, Guido Iaccarino, Guido Tarone, Denise Hilfiker‐Kleiner, Johann Bauersachs, Adelino F. Leite‐Moreira, Peter H. Sugden, Jean‐Luc Balligand
Journal: European Journal of Heart Failure (2011)
Out of America to Africa or Asia: Inference of Dispersal Histories Using Nuclear and Plastid DNA and the S-RNase Self-incompatibility Locus
Authors: Jill S. Miller, Ambika Kamath, Julian Damashek, Rachel A. Levin
Journal: Molecular Biology and Evolution (2010)

The plant genus Lycium (Solanaceae) originated in the Americas and includes approximately 85 species that are distributed worldwide. The vast majority of Old World species occur in southern Africa and eastern Asia. In this study, we examine biogeographic relationships among Old World species using a phylogenetic approach coupled with molecular evolutionary analyses of the S-RNase self-incompatibility gene. The phylogeny inferred from nuclear granule-bound starch synthase I (GBSSI), nuclear conserved ortholog set II (COSII) marker C2_At1g24360, and plastid spacer data (trnH-pbsA, trnDGUC–trnTGGU, rpl32–trnLUAG, and ndhF–rpl32) includes a clade of eastern Asian Lycium nested within the African species, suggesting initial dispersal from the Americas to Africa, with subsequent dispersal to eastern Asia. Molecular dating estimates suggest that these dispersal events occurred relatively recently, with dispersal from the Americas to Africa approximately 3.64 Ma (95% highest posterior density [HPD]: 1.58–6.27), followed by subsequent dispersal to eastern Asia approximately 1.21 Ma (95% HPD: 0.32–2.42). In accordance, the S-RNase genealogy shows that S-RNases isolated from Old World species are restricted to four lineages, a subset of the 14 lineages including S-RNases isolated from New World Lycium species, supporting a bottleneck of S-RNase alleles concomitant with a single dispersal event from the Americas to the Old World. Furthermore, the S-RNase genealogy is also consistent with dispersal of Lycium from Africa to Asia, as eastern Asian alleles are restricted to a subset of the lineages that also include African alleles. Such a multilocus approach, including complementary data from GBSSI, COSII, plastid spacer regions, and S-RNase, is powerful for understanding dispersal histories of closely related species.
Structure-Activity Relationships and Specificity of Inhibition of DNA Polymerases From Normal and Leukemia Cells of Man and From Simian Sarcoma Virus by and and Rifamycin Derivatives2
Authors: Richard A. DiCioccio, B. I. Sahai Srivastava
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Structure-Activity Relationships and Specificity of Inhibition of DNA Polymerases From Normal and Leukemia Cells of Man and From Simian Sarcoma Virus by and and Rifamycin Derivatives Get access Richard A. DiCioccio, Richard A. DiCioccio 3Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute. 666 Elm St., New York State Department of Health, Buffalo, N.Y. 14263. Search for other works by this author on: Oxford Academic PubMed Google Scholar B. I. Sahai Srivastava B. I. Sahai Srivastava 4 3Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Memorial Institute. 666 Elm St., New York State Department of Health, Buffalo, N.Y. 14263. 5We thank Professor Giancarlo Lancini, Gruppo Lepetit, Milan, Italy, for his generous gift of rifamycin derivatives and Dr. Harry B. Wood, Jr., Drug Development Branch. Division of Cancer Treatment, National Cancer Institute, Bethesda, Md., for his help in obtaining these compounds. 4Address reprint requests to Dr. Srivastava. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 5, November 1978, Pages 1187–1194, https://doi.org/10.1093/jnci/61.5.1187 Published: 01 November 1978 Article history Received: 10 March 1978 Accepted: 03 July 1978 Published: 01 November 1978
Suppression of HIV-1 Expression by Inhibitors of Cyclin-Dependent Kinases Promotes Differentiation of Infected Podocytes
Authors: Peter J. Nelson, Irwin H. Gelman, Paul E. Klotman
Journal: Journal of the American Society of Nephrology (2001)

The glomerular lesions of HIV-associated nephropathy (HIVAN) are associated with the expression of HIV-1 in podocytes. Infected podocytes proliferate and lose several differentiation markers in vivo and in vitro, which suggests that HIV-1 gene expression induces these changes. Flavopiridol and roscovitine, newly identified inhibitors of cyclin-dependent kinase-9, markedly decrease HIV-1 promoter activity in cell lines of various lineages. In this study, the inhibitors were used to determine whether suppression of HIV-1 transcription in infected podocytes correlated with an inhibition of proliferation and a return to the differentiated phenotype. Dose-response analysis showed that both flavopiridol and roscovitine reversibly suppressed HIV-1 transcription in podocytes in vitro at an IC(50) of 25 nM and 3 microM, respectively. Despite equivalent suppression of HIV-1 transcription, roscovitine was a more effective inhibitor of podocyte proliferation than flavopiridol. Suppression of HIV-1 transcription by flavopiridol or roscovitine was marked by re-expression of the podocyte differentiation markers, synaptopodin and podocalyxin. These results suggest that inhibition of HIV-1 transcription decreases podocyte proliferation and permits the reexpression of differentiation markers. Thus, suppression of HIV-1 transcription by selective cyclin-dependent kinase-9 inhibitors may be a useful therapeutic strategy for the treatment of HIVAN.