tbuckley/cabot-search huggingface dataset:
Serum IgA, acute phase proteins, and glycosylation of alpha 1-acid glycoprotein in ankylosing spondylitis.
Authors: A Mackiewicz, M A Khan, T L Reynolds, S van der Linden, I Kushner
Journal: Annals of the Rheumatic Diseases (1989)

Several investigators have suggested that gastrointestinal inflammation has a role in the pathogenesis of ankylosing spondylitis. To test this hypothesis markers of gastrointestinal immunostimulation, as manifested by serum IgA concentrations, were compared with serum markers of inflammation, as manifested by acute phase proteins. Serum samples from 45 unrelated Caucasian patients with ankylosing spondylitis (AS) were tested for correlation of serum IgA and six acute phase proteins: C reactive protein (CRP), alpha 1-antitrypsin, alpha 1-antichymotrypsin, caeruloplasmin, alpha 1-acid glycoprotein (AGP), and haptoglobin. Serum IgA was shown to be significantly positively correlated with four of these six acute phase proteins: CRP (r = 0.58, p less than 0.001), alpha 1-antitrypsin (r = 0.29, p less than 0.05), AGP (r = 0.61, p less than 0.01), and haptoglobin (r = 0.58, p less than 0.001), suggesting that gastrointestinal immunostimulation does have a role in the pathogenesis of inflammation in AS. In addition, the microheterogeneity of the pattern of glycosylation of AGP, expressed as reactivity coefficients, was examined. The AGP reactivity coefficient has been shown to increase in infection, remain the same in systemic lupus erythematosus, and decrease in rheumatoid arthritis. It was found that the AGP reactivity coefficient was significantly decreased in patients with AS as compared with healthy controls (p less than 0.006). As recent studies have indicated that patterns of glycosylation reflect intrahepatocellular biosynthetic processes induced by cytokines our data suggest that cytokine-hepatocellular mechanisms in AS may be similar to those occurring in rheumatoid arthritis, but different from those in systemic lupus erythematosus or infection.
Long-Term Cardiovascular Mortality in Patients With Differentiated Thyroid Carcinoma: An Observational Study
Authors: Esther N. Klein Hesselink, Mariëlle S. Klein Hesselink, Geertruida H. de Bock, Ron T. Gansevoort, Stephan J.L. Bakker, Eline J. Vredeveld, Anouk N.A. van der Horst-Schrivers, Iwan C.C. van der Horst, Pieter W. Kamphuisen, John T.M. Plukker, Thera P. Links, Joop D. Lefrandt
Journal: Journal of Clinical Oncology (2013)

Purpose The primary aim was to study the risk of cardiovascular mortality in patients with differentiated thyroid carcinoma (DTC). Secondary aims were to evaluate all-cause mortality and explore the relation between thyroid-stimulating hormone (TSH; also known as thyrotropin) level and these outcome parameters. Patients and Methods Subjects from two cohorts were retrospectively compared by Cox regression analyses; 524 patients with DTC and 1,572 sex- and age-matched controls from a large population-based study in the same geographic region. Results Mean age plus or minus standard deviation was 49 ± 14 years. Median follow-up was 8.5 years (interquartile range [IQR], 4.1 to 15.9 years) for patients with DTC and 10.5 years (IQR, 9.9 to 10.9 years) for controls. One hundred patients with DTC (19.1%) died, 22 (4.2%) as a result of cardiovascular disease, 39 (7.4%) as a result of DTC, and 39 (7.4%) as a result of other/unknown causes. Eighty-five controls (5.4%) died, 24 (1.5%) as a result of cardiovascular disease and 61 (3.9%) as a result of other/unknown causes. Patients with DTC had an increased risk of cardiovascular and all-cause mortality (hazard ratios [HRs], 3.35 [95% CI, 1.66 to 6.74] and 4.40 [95% CI, 3.15 to 6.14], respectively, adjusted for age, sex, and cardiovascular risk factors). Within the DTC group, TSH level was predictive for cardiovascular mortality; the adjusted HR was 3.08 (95% CI, 1.32 to 7.21) for each 10-fold decrease in geometric mean TSH level. Conclusion The risk of cardiovascular and all-cause mortality is increased in patients with DTC, independent of age, sex, and cardiovascular risk factors. A lower TSH level is associated with increased cardiovascular mortality, supporting the current European Thyroid Association and the American Thyroid Association guidelines of tempering TSH suppression in patients with low risk of cancer recurrence. Furthermore, patients with DTC may benefit from assessment and treatment of cardiovascular risk factors.
MicroRNA-Mediated Inhibition of Prostate-Derived Ets Factor Messenger RNA Translation Affects Prostate-Derived Ets Factor Regulatory Networks in Human Breast Cancer
Authors: Victoria J. Findlay, David P. Turner, Omar Moussa, Dennis K. Watson
Journal: Cancer Research (2008)

Abstract Prostate-derived Ets factor (PDEF) is an ETS transcription factor expressed in normal tissues with high epithelial cell content and noninvasive breast cancer cells. A putative tumor suppressor PDEF protein expression is often lost during progression to a more invasive phenotype. Interestingly, PDEF mRNA has been found to be retained or even overexpressed in the absence of protein; however, the mechanisms for this remain to be elucidated. This study identifies two microRNAs (miRNA) that directly act on and repress PDEF mRNA translation, leading to the loss of PDEF protein expression and the gain of phenotypes associated with invasive cells. In addition, we show that these miRNAs are elevated in human breast tumor samples. Together, these data describe a mechanism of regulation that explains, for the first time, the lack of correlation between PDEF mRNA and protein levels, providing insight into the underexplored role of posttranscriptional regulation and how this contributes to dysregulated protein expression in cancer. These observations have critical implications for therapeutically targeting miRNAs that contribute to cancer progression. [Cancer Res 2008;68(20):8499–506]
A Fully Human Monoclonal Antibody (CR002) Identifies PDGF-D as a Novel Mediator of Mesangioproliferative Glomerulonephritis
Authors: Tammo Ostendorf, Claudia R.C. van Roeyen, Jeffrey D. Peterson, Uta Kunter, Frank Eitner, Avin J. Hamad, Gerlinde Chan, Xiao-Chi Jia, Jennifer Macaluso, Gadi Gazit-Bornstein, Bruce A. Keyt, Henri S. Lichenstein, William J. LaRochelle, Jürgen Floege
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. PDGF-B is of central importance in mesangioproliferative diseases. PDGF-D, a new PDGF isoform, like PDGF-B, signals through the PDGF ββ-receptor. The present study first determined that PDGF-D is mitogenic for rat mesangial cells and is not inhibited by a PDGF-B antagonist. Low levels of PDGF-D mRNA were detected in normal rat glomeruli. After induction of mesangioproliferative nephritis in rats by anti–Thy 1.1 mAb, glomerular PDGF-D mRNA and protein expression increased significantly from days 4 to 9 in comparison with nonnephritic rats. Peak expression of PDGF-D mRNA occurred 2 d later than peak PDGF-B mRNA expression. In addition, PDGF-D serum levels increased significantly in the nephritic animals on day 7. For investigating the functional role of PDGF-D, neutralizing fully human mAb were generated using the XenoMouse technology. Rats with anti–Thy 1.1–induced nephritis were treated on days 3 and 5 with different amounts of a fully human PDGF-DD–specific neutralizing mAb (CR002), equal amounts of irrelevant control mAb, or PBS by intraperitoneal injection. Specific antagonism of PDGF-D led to a dose-dependent (up to 67%) reduction of glomerular cell proliferation. As judged by double immunostaining for 5-bromo-2′-deoxyuridine and α-smooth muscle actin, glomerular mesangial cell proliferation was reduced by up to 57%. Reduction of glomerular cell proliferation in the rats that received CR002 was not associated with reduced glomerular expression of PDGF-B mRNA. PDGF-D antagonism also led to reduced glomerular infiltration of monocytes/macrophages (day 5) and reduced accumulation of fibronectin (day 8). In contrast, no effect was noted in normal rats that received an injection of CR002. These data show that PDGF-D is overexpressed in mesangioproliferative states and can act as an auto-, para-, or even endocrine glomerular cell mitogen, indicating that antagonism of PDGF-D may represent a novel therapeutic approach to mesangioproliferative glomerulonephritides. E-mail: juergen.floege@rwth-aachen.de
Ultrasound and Doppler findings in the Achilles tendon among middle-aged recreational floor-ball players in direct relation to a match: Figure 1
Authors: M Fahlström, H Alfredson
Journal: British Journal of Sports Medicine (2008)

Objective In this study, structure, blood flow and thickness in the Achilles tendon related to tendon-loading activity were investigated. Design Examination by ultrasound (US) and colour Doppler (CD) immediately before and after 1 h of floor-ball matchplay. Setting Sports Medicine Unit, Umeå University, Sweden Participants 36 Achilles tendons in 18 middle-aged (mean 39 years) recreational male floor-ball players. Main outcome measurements Structure and high blood flow (HBF)/neovessels (NV) in the tendons were registered. Tendon thickness was measured 3 and 4.5 cm above the upper calcaneus and at the thickest part of the tendon. Results The US examination showed that 11/36 tendons (30.5%) in nine individuals had structural changes before and after the floor-ball match. In 7/36 tendons (five with structural changes), there were HBF/NV before, and after, the match. In six of these seven tendons, the blood flow was higher after than before the match. In three more tendons (two with structural changes), there were HBF/NV after, but not before, the match. After the match, mean tendon thickness had decreased significantly in both normal tendons and tendons with structural changes at the 3-cm level (6.0 (1.0) mm to 5.8 (0.9) mm; p&lt;0.019), at the 4.5-cm level (5.7 (1.1) mm to 5.5 (1.0) mm; p&lt;0.044), and at the thickest part (6.6 (1.1) mm to 6.3 (1.2) mm; p&lt;0.000). Conclusions In about 1/3 of the tendons, there were structural changes, about half of those tendons also had HBF/NV, which was higher after, than before, the match. Mean tendon thickness in both normal tendons and tendons with structural changes had decreased significantly after a 1-h floor-ball match.
Mitochondrial DNA haplogroups modulate the serum levels of biomarkers in patients with osteoarthritis
Authors: I. Rego-Perez, M. Fernandez-Moreno, M. Deberg, S. Pertega, C. Fenandez-Lopez, N. Oreiro, Y. Henrotin, F. J. Blanco
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> To analyse the influence of mitochondrial DNA (mtDNA) haplogroups on serum levels of molecular biomarkers in patients with osteoarthritis (OA). <h3>Methods</h3> Serum levels of molecular biomarkers of cartilage metabolism (collagen type II markers: C-terminal neoepitope generated by the collagenase-mediated cleavage of collagen type II triple helix (C2C), collagen type II (Coll2-1, and its nitrated form, Coll2-1NO<sub>2</sub>), procollagen type II (CPII)), synovial metabolism (hyaluronic acid (HA)) and cartilage and synovial turnover (cartilage glycoprotein 39 (YKL-40)) were analysed in 73 patients with OA and 77 healthy controls using ELISAs. All participants had been previously genotyped for the mtDNA haplogroups J, U and H. Non-parametric and multivariate analysis were performed to test the effects of the clinical variables, including gender, age, smoking status, diagnosis, mtDNA haplogroups and radiological Kellgren and Lawrence (K/L) grade on the serum levels of the molecular markers. <h3>Results</h3> Non-parametric analysis found increased serum levels of HA in patients with OA, while the values for C2C and the C2C/CPII ratio were significantly higher in the healthy controls. A multiple regression analysis showed a relationship between the mtDNA haplogroups and serum levels of the typical collagen type II markers. Carriers of the mtDNA haplogroup H had higher levels while carriers of the mtDNA haplogroup J showed lower levels. Statistically significant interactions between mtDNA haplogroups and diagnosis and between mtDNA haplogroups and radiological K/L grade in the serum levels of molecular markers were also found. <h3>Conclusion</h3> A new role for mtDNA haplogroups emerges from this work. The results suggest that the mtDNA haplogroups interact significantly with the serum levels of OA-related molecular markers, suggesting the possibility of their use as a complementary assay with these molecular markers.
Assessment of anorectal function in selection of patients for ileorectal anastomosis in Crohn's colitis.
Authors: M R Keighley, P Buchmann, J R Lee
Journal: Gut (1982)

Anorectal function has been assessed in 53 patients with Crohn9s disease by measurement of resting and squeeze anal canal pressures and the maximum volume tolerated during distension of a balloon in the rectum. Radiographs of the rectum from barium enema examination were also reviewed to assess rectal capacity. Thirty-three patients have had a colectomy and ileorectal anastomosis for Crohn9s colitis of whom 13 now have a stoma because they either required a protectomy (n=9) or where closure of a loop ileostomy had not been possible (n=4) because of severe anorectal disease. The maximum tolerated volume was less than 150 ml in 12 of 13 patients who now have a stoma compared with none of the 20 patients who have a functioning anastomosis. Although the correlation between a radiological assessment of rectal capacity and the maximum tolerated volume was poor, a severely contracted rectum was associated with the need for a stoma in six of seven patients compared with only two of 13 patients who did not have radiological signs of a narrow rectum.
Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer
Authors: M. Hickey, C. Saunders, A. Partridge, N. Santoro, H. Joffe, V. Stearns
Journal: Annals of Oncology (2008)

The purpose of this study was to provide practical, evidence-based guidelines for evaluating and treating common menopausal symptoms following breast cancer.Literature review of the causes, assessment and management of menopausal symptoms in breast cancer patients.A number of nonhormonal treatments are effective in treating hot flashes. Whether pharmacological treatment is given will depend on the severity of symptoms and on patient wishes. For severe and frequent hot flashes, the best data support the use of venlafaxine, paroxetine and gabapentin in women with breast cancer. Side-effects are relatively common with all these agents. For vaginal dryness, topical estrogen treatment is the most effective but the safety of estrogens following breast cancer is not established. There are limited data on effective treatments for sexual dysfunction during menopause.Menopausal symptoms after breast cancer should be evaluated and managed as warranted using a systematic approach and may benefit from multidisciplinary input.
Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases.
Authors: R R Reinhardt, E Chin, J Zhou, M Taira, T Murata, V C Manganiello, C A Bondy
Journal: Journal of Clinical Investigation (1995)

Type III cGMP-inhibited phosphodiesterases (PDE3s) play important roles in hormonal regulation of lipolysis, platelet aggregation, myocardial contractility, and smooth muscle relaxation. We have recently characterized two PDE3 subtypes (PDE3A and PDE3B) as products of distinct but related genes. To elucidate their biological roles, in this study we compare cellular patterns of gene expression for these two enzymes during rat embryonic and postnatal development using in situ hybridization. PDE3B [corrected] mRNA is abundant in adipose tissue and is also expressed in hepatocytes throughout development. This mRNA is also highly abundant in embryonic neuroepithelium including the neural retina, but expression is greatly reduced in the mature nervous system. Finally, PDE3B [corrected] mRNA is localized in spermatocytes and renal collecting duct epithelium in adult rats. PDE3B mRNA is highly expressed in the cardiovascular system, including myocardium and arterial and venous smooth muscle, throughout development. It is also abundant in bronchial, genitourinary and gastrointestinal smooth muscle and epithelium, megakaryocytes, and oocytes. PDE3A [corrected] mRNA demonstrates a complex, developmentally regulated pattern of gene expression in the central nervous system. In summary, the two different PDE3s show distinctive tissue-specific patterns of gene expression suggesting that PDE3B [corrected] is involved in hormonal regulation of lipolysis and glycogenolysis, while regulation of myocardial and smooth muscle contractility appears to be a function of PDE3A [corrected]. In addition, the present findings suggest previously unsuspected roles for these enzymes in gametogenesis and neural development.
Reducing Ryanodine Receptor Open Probability as a Means to Abolish Spontaneous Ca <sup>2+</sup> Release and Increase Ca <sup>2+</sup> Transient Amplitude in Adult Ventricular Myocytes
Authors: L.A. Venetucci, A.W. Trafford, M.E. Díaz, S.C. O’Neill, D.A. Eisner
Journal: Circulation Research (2006)

The aim of this work was to investigate whether it is possible to remove arrhythmogenic Ca 2+ release from the sarcoplasmic reticulum that occurs in calcium overload without compromising normal systolic release. Exposure of rat ventricular myocytes to isoproterenol (1 μmol/L) resulted in an increased amplitude of the systolic Ca 2+ transient and the appearance of waves of diastolic Ca 2+ release. Application of tetracaine (25 to 50 μmol/L) decreased the frequency or abolished the diastolic Ca 2+ release. This was accompanied by an increase in the amplitude of the systolic Ca 2+ transient. Cellular Ca 2+ flux balance was investigated by integrating Ca 2+ entry (on the L-type Ca 2+ current) and efflux (on Na–Ca 2+ exchange). Isoproterenol increased Ca 2+ influx but failed to increase Ca 2+ efflux during systole (because of the abbreviation of the duration of the Ca 2+ transient). To match this increased influx the bulk of Ca 2+ efflux occurred via Na–Ca 2+ exchange during a diastolic Ca 2+ wave. Subsequent application of tetracaine increased systolic Ca 2+ efflux and abolished the diastolic efflux. The increase of systolic efflux in tetracaine resulted from both increased amplitude and duration of the systolic Ca 2+ transient. In the presence of isoproterenol, those Ca 2+ transients preceded by diastolic release were smaller than those where no diastolic release had occurred. When tetracaine was added, the amplitude of the Ca 2+ transient was similar to those in isoproterenol with no diastolic release and larger than those preceded by diastolic release. We conclude that tetracaine increases the amplitude of the systolic Ca 2+ transient by removing the inhibitory effect of diastolic Ca 2+ release.
Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies
Authors: Isabel dos Santos Silva, Bianca De Stavola, Valerie McCormack
Journal: PLoS Medicine (2008)

Isobel dos Santos Silva and Bianca De Stavola and colleagues reanalyzed individual participant data from 32 published and unpublished studies to obtain precise estimates of the association between birth size and breast cancer risk.
A phosphatase activity present in peripheral blood myeloid cells of chronic myelogenous leukemia patients but not normal individuals alters nuclear protein binding to transcriptional enhancers of interferon-inducible genes.
Authors: D C Seong, S Sims, E Johnson, O M Howard, B Reiter, J Hester, M Talpaz, H Kantarjian, A Deisseroth
Journal: Journal of Clinical Investigation (1990)

Cytoplasmic protein from peripheral blood myeloid cells of chronic myelogenous leukemia (CML) patients altered the electrophoretic mobility of complexes formed between nuclear proteins and interferon-inducible transcriptional enhancers. Immature myeloid marrow cells (blasts and promyelocytes) have a higher level of this activity than do mature myeloid marrow cells (bands and polys). This activity, which is not detectable in the peripheral blood cells of normal individuals, is at least 50-fold higher in CML marrow blasts and promyelocytes than that found in marrow blasts and promyelocytes of normal individuals. This activity was inhibited by in vivo incubation of immature myeloid cells with the phosphatase inhibitor, sodium orthovanadate (0.2 mM), and by adding orthovanadate (20 mM) directly to cytoplasmic proteins of myeloid cells. Interferon-alpha (1,000 U/ml) reduced the effects of the CML myeloid cell cytoplasmic protein on the electrophoretic mobility of nuclear protein-DNA complexes. These data suggest that a unique phosphatase may be involved in the abnormalities in CML which are modulated by interferon-alpha.
Broad applications of single-cell nucleic acid analysis in biomedical research
Authors: Michael Wigler
Journal: Genome Medicine (2012)

Recent publications have demonstrated the feasibility and utility of sequencing DNA or RNA from single cells [1,2].Th e power of these tools lies in their ability to reveal in mixtures of cells the identity and state of sub populations.Th e advantage of singlecell analysis over merely deep sequencing, whether for DNA or RNA, lies in the ability of the former to isolate diff erences and to phase possibly multiple diff erences within subpopu la tions.Th e future applications of these technologies are the topic of this brief article.I will assume throughout that in the near future assess ing both DNA and RNA content simultaneously from hundreds to thousands of single cells will be quanti tatively accurate, as complete as needed, and aff ordable.It follows from these assumptions that knowledge of chromatin confi guration and DNA methylation in single cells will also be attainable.I will not consider what is possible by assaying the protein content of single cells, either by microscopy or mass spectroscopy, or by using methods not yet invented.Also, I will not focus on the many applications of this technology in oncology, such as in outcome research and early detection, as these appli ca tions are ongoing and have been widely discussed else where [3].Instead, I want to speculate on basic applica tions to cell biology, theory of disease and diagnosis.
Molecular Imaging of Chemokine Receptor CXCR4
Authors: Ido. D. Weiss, Orit Jacobson
Journal: Theranostics (2013)

CXCR4 was found to be expressed by many different types of human cancers and its expression has been correlated with tumor aggressiveness, poor prognosis and resistance to chemotherapy.CXCR4 was also shown to contribute to metastatic seeding of organs that express its ligand CXCL12 and support the survival of these cells.These findings suggest that CXCR4 is a potentially attractive therapeutic target, and several antagonists and antibodies for this receptor were developed and are under clinical evaluation.Quantifying CXCR4 expression non-invasively might aid in prognostication as a mean for personalized therapy and post treatment monitoring.Multiple attempts were done over the recent years to develop imaging agents for CXCR4 using different technologies including PET, SPECT, fluorescent and bioluminescence, and will be reviewed in this paper.