tbuckley/cabot-search huggingface dataset:
MRI of hand and foot joints of patients with anticitrullinated peptide antibody positive arthralgia without clinical arthritis
Authors: Annemarie Krabben, Wouter Stomp, Désirée M F M van der Heijde, Jessica A B van Nies, Johan L Bloem, Tom W J Huizinga, Monique Reijnierse, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

Anticitrullinated peptide antibodies (ACPA) and acute phase reactants may be increased before arthritis becomes clinically detectable, suggesting that the processes underlying rheumatoid arthritis (RA) start preclinically. Whether local inflammation occurs in the preclinical phase is unknown. Therefore, we studied the small joints of ACPA positive arthralgia patients for local subclinical inflammation.Imaging was performed using 1.5 T extremity MRI. Painful hand or foot joints of 21 ACPA positive arthralgia patients without clinical arthritis were imaged. For comparison, hand and foot joints of 22 ACPA positive RA patients and 19 symptom free controls were studied. Within ACPA positive arthralgia patients, painful and symptom free joint regions were imaged. Scoring was performed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) method. Analyses were performed on joint region level and focused on inflammation (synovitis plus bone marrow oedema).The mean combined inflammation scores of the metacarpophalangeal/proximal interphalangeal joints of controls, painful joints of ACPA positive arthralgia patients and ACPA positive RA patients were 0.1, 0.7 and 3.7, respectively (p<0.001). Likewise, the mean combined inflammation scores of the wrist were 0.9, 2.3 and 10.3, respectively (p<0.001) and that of the metatarsophalangeal joints 0.5, 0.9 and 3.8, respectively (p=0.10). At the MCP joints, the combined inflammation score was significantly correlated with C reactive protein and erythrocyte sedimentation rate levels (rs=0.83 and rs=0.78, respectively)The present data suggest that local subclinical inflammation occurs in ACPA positive arthralgia patients.
Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40
Authors: A W Rijneveld, B van der Holt, S M G J Daenen, B J Biemond, O de Weerdt, P Muus, J Maertens, V Mattijssen, H Demuynck, M C J C Legdeur, P W Wijermans, S Wittebol, F M Spoelstra, A W Dekker, G J Ossenkoppele, R Willemze, J J Cornelissen
Journal: Leukemia (2011)
Prenatal acetaminophen induces liver toxicity in dams, reduces fetal liver stem cells, and increases airway inflammation in adult offspring
Authors: Khalil Karimi, Timo Keßler, Kristin Thiele, Katherina Ramisch, Annette Erhardt, Peter Huebener, Roja Barikbin, Petra Arck, Gisa Tiegs
Journal: Journal of Hepatology (2014)
Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy
Authors: Y. Xu, L. Diao, Y. Chen, Y. Liu, C. Wang, T. Ouyang, J. Li, T. Wang, Z. Fan, T. Fan, B. Lin, D. Deng, S.A. Narod, Y. Xie
Journal: Annals of Oncology (2013)
Renal Ischemia/Reperfusion Injury
Authors: Ana Molina, María Ubeda, María M Escribese, Laura García-Bermejo, David Sancho, Guillermo Pérez de Lema, Fernando Liaño, Carlos Cabañas, Francisco Sánchez-Madrid, Francisco Mampaso
Journal: Journal of the American Society of Nephrology (2004)

Renal ischemia/reperfusion injury (IRI) is an important cause of acute renal failure. Cellular and molecular responses of the kidney to IRI are complex and not fully understood. beta1 integrins localize to the basal surface of tubular epithelium interacting with extracellular matrix components of the basal membrane, including collagen IV. Whether preservation of tubular epithelium integrity could be a therapeutic approach for IRI was assessed. The effects of HUTS-21 mAb administration, which recognizes an activation-dependent epitope of beta1 integrins, in a rat model of IRI were investigated. Preischemic HUTS-21 administration resulted in the preservation of renal functional and histopathologic parameters. Analyses of activated beta1 integrins expression and focal adhesion kinase phosphorylation suggest that its deactivation after IRI was prevented by HUTS-21 treatment. Moreover, HUTS-21 impaired the inflammatory response in vivo, as indicated by inhibition of proinflammatory mediators and the absence of infiltrating cells. Ex vivo adhesion assays using reperfused kidneys revealed that HUTS-21 induced a significant increase of epithelial cell attachment to collagen IV. In conclusion, the data provide evidence that HUTS-21 has a protective effect in renal IRI, preventing tubular epithelial cell detachment by preserving activated beta1 integrins functions.
Prevention of Murine Radiogenic Thymic Lymphomas by Tumor Necrosis Factor or by Marrow Grafting
Authors: C. Humblet, R. Greimers, P. Delvenne, J. Deman, J. Boniver, M. P. Defresne
Journal: JNCI Journal of the National Cancer Institute (1996)

Split-dose irradiation (1.75 Gy given weekly for 4 weeks) of C57BL/Ka mice induces the emergence of preleukemic cells (PLCs). These cells develop into leukemic cells after a latency period of 3–6 months. The survival and transformation of PLCs are dependent on radiation-induced alterations of the thymic epithelium and of resident lymphocyte (i.e., thymocyte) subpopulations in the thymus. PLCs can be eliminated, concomitantly with the restoration of the thymus, by grafting bone marrow cells immediately after the last irradiation. Our hypothesis was that any agent able to restore the thymus after leukemogenic irradiation would exert the same effects as a bone marrow graft. Tumor necrosis factor-α (TNF-α) is one such possible agent, since it has been shown to modulate some functions of the thymic epithelium and thymocyte subpopulations. The goal of this study was to assess the ability of repeated intraperitoneal injections of TNF-α to functionally replace bone marrow transplantation in the restoration of normal intrathymic lymphopoiesis and in the prevention of thymic lymphomas in split-dose-irradiated mice. We replaced the bone marrow graft with repeated injections of TNF-α (25 000 U/injection) in the split-dose-irradiated (4 × 1.75 Gy) C57BL/Ka mouse model. We analyzed the expression of the cell differentiation markers CD4 and CD8 on thymocytes by flow cytometry. We also studied the thymic environment by isolating thymic nurse cells, the bone marrow prothymocyte activity by analyzing thymic repopulation, and the evolution of PLCs by an in vivo transplantation assay. Local production of TNF-α after bone marrow grafting was examined by in situ hybridization. Injections of anti-TNF-α antibodies were given to split-dose-irradiated mice to test the effect of neutralizing TNF-α in vivo. One-way analysis of variance and New-man-Keuls two-tailed tests were used to test statistical significance. Multiple injections of TNF-α into split-dose-irradiated mice did not influence bone marrow prothymocyte activity but restored thymocyte subpopulations and thymic epithelium, induced the disappearance of PLCs, and prevented the development of lymphomas. Moreover, a bone marrow graft significantly stimulated intrathymic production of TNF-α messenger RNA ( P <.01), and anti-TNF-α antibodies partially inhibited the antilymphomatous effects of bone marrow graft in split-dose-irradiated mice ( P <.05). These data strongly suggest that TNF-α is a mediator that is involved in the mechanisms by which bone marrow transplantation functions to prevent thymic lymphomas in split-dose-irradiated mice. Cytokines might be used in some biological systems, particularly in the hemopoietic system, as a therapeutic agent for the secondary prevention of cancer.
Impact of Insulin Resistance on Risk of Type 2 Diabetes and Cardiovascular Disease in People With Metabolic Syndrome
Authors: James B. Meigs, Martin K. Rutter, Lisa M. Sullivan, Caroline S. Fox, Ralph B. D'Agostino, Peter W.F. Wilson
Journal: Diabetes Care (2007)

Metabolic syndrome increases the risk for type 2 diabetes and cardiovascular disease (CVD) and may be associated with insulin resistance.We tested the hypothesis that the metabolic syndrome confers risk with or without concomitant insulin resistance among 2,803 Framingham Offspring Study subjects followed up to 11 years for new diabetes (135 cases) or CVD (240 cases). We classified subjects by presence of metabolic syndrome (using the National Cholesterol Education Program's [NCEPs] Third Adult Treatment Panel [ATP III], International Diabetes Federation [IDF], or European Group for the Study of Insulin Resistance [EGIR] criteria) and insulin resistance (homeostasis model assessment of insulin resistance > or = 75th percentile) and used separate risk factor-adjusted proportional hazards models to estimate relative risks (RRs) for diabetes or CVD using as referents those without insulin resistance, metabolic syndrome, or without both.Fifty-six percent of individuals with ATP III, 52% with IDF, and 100% with EGIR definitions of metabolic syndrome had insulin resistance. Insulin resistance increased risk for diabetes (RR 2.6 [95% CI 1.7-4.0]) and CVD (1.8 [1.4-2.3]) as did metabolic syndrome for diabetes (ATP III, 3.5 [2.2-5.6]; IDF, 4.6 [2.7-7.7]; and EGIR, 3.3 [2.1-5.1]) and CVD (ATP III, 1.8 [1.4-2.3]; IDF, 1.7 [1.3-2.3]; and EGIR, 2.1 [1.6-2.7]). Relative to those without either metabolic syndrome or insulin resistance, metabolic syndrome and insulin resistance increased risk for diabetes (ATP III, 6.0 [3.3-10.8] and IDF, 6.9 [3.7-13.0]) and CVD (ATP III, 2.3 [1.7-3.1] and IDF, 2.2 [1.6-3.0]). Any instance of metabolic syndrome without insulin resistance increased risk for diabetes approximately threefold (P < 0.001); IDF metabolic syndrome without insulin resistance (RR 1.6, P = 0.01), but not ATP III metabolic syndrome without insulin resistance (RR 1.3, P = 0.2), increased risk for CVD.Metabolic syndrome increased risk for diabetes regardless of insulin resistance. Metabolic syndrome by ATP III criteria may require insulin resistance to increase risk for CVD. The simultaneous presence of metabolic syndrome and insulin resistance identifies an especially high-risk individual.
Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors
Authors: H. Boer, J.H. Proost, J. Nuver, S. Bunskoek, J.Q. Gietema, B.M. Geubels, R. Altena, N. Zwart, S.F. Oosting, J.M. Vonk, J.D. Lefrandt, D.R.A. Uges, C. Meijer, E.G.E. de Vries, J.A. Gietema
Journal: Annals of Oncology (2015)

BackgroundThe success of cisplatin-based (Platinol, Bristol-Myers Squibb Company, New York, NY, USA) chemotherapy for testicular cancer comes at the price of long-term and late effects related to healthy tissue damage. We assessed and modelled serum platinum (Pt) decay after chemotherapy and determined relationships between long-term circulating Pt levels and known late effects.Patients and methodsIn 99 testicular cancer survivors, treated with cisplatin-based chemotherapy, serum and 24-h urine samples were collected during follow-up (1–13 years after treatment). To build a population pharmacokinetic model, measured Pt data were simultaneously analysed, together with cisplatin dose, age, weight and height using the NONMEM software. Based on this model, area under the curve between 1 and 3 years after treatment (Pt AUC1–3 years) was calculated for each patient. Predicted long-term Pt exposure was related to renal function and to late effects of treatment assessed median 9 (3–15) years after chemotherapy.ResultsDecay of Pt was best described by a two-compartment model. Mean terminal T1/2 was 3.7 (range 2.5–5.2) years. Pt AUC1–3 years correlated with cumulative cisplatin dose, and creatinine clearance before and 1 year after treatment. Patients with paraesthesia had higher Pt AUC1–3 years (30.9 versus 27.0 µg/l month) compared with those without paraesthesia (P = 0.021). Patients with hypogonadism, elevated LDL-cholesterol levels or hypertension also had higher Pt AUC1–3 years.ConclusionsRenal function before and after cisplatin treatment is an important determinant of long-term Pt exposure. Known long-term effects of testicular cancer treatment, such as paraesthesia, hypogonadism, hypercholesterolaemia and hypertension, are associated with long-term circulating Pt exposure.
The Phylogenetic Relationship of Tetrapod, Coelacanth, and Lungfish Revealed by the Sequences of Forty-Four Nuclear Genes
Authors: Naoko Takezaki, Felipe Figueroa, Zofia Zaleska-Rutczynska, Naoyuki Takahata, Jan Klein
Journal: Molecular Biology and Evolution (2004)

The origin of tetrapods is a major outstanding issue in vertebrate phylogeny. Each of the three possible principal hypotheses (coelacanth, lungfish, or neither being the sister group of tetrapods) has found support in different sets of data. In an attempt to resolve the controversy, sequences of 44 nuclear genes encoding amino acid residues at 10,404 positions were obtained and analyzed. However, this large set of sequences did not support conclusively one of the three hypotheses. Apparently, the coelacanth, lungfish, and tetrapod lineages diverged within such a short time interval that at this level of analysis, their relationships appear to be an irresolvable trichotomy.
The Phosphoinositide 3-Kinase Regulatory Subunit p85α Can Exert Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling
Authors: Cullen M. Taniguchi, Jonathon Winnay, Tatsuya Kondo, Roderick T. Bronson, Alexander R. Guimaraes, José O. Alemán, Ji Luo, Gregory Stephanopoulos, Ralph Weissleder, Lewis C. Cantley, C. Ronald Kahn
Journal: Cancer Research (2010)

Abstract Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, and the PI3K p85 regulatory subunit exerts both positive and negative effects on signaling. Expression of Pik3r1, the gene encoding p85, is decreased in human prostate, lung, ovarian, bladder, and liver cancers, consistent with the possibility that p85 has tumor suppressor properties. We tested this hypothesis by studying mice with a liver-specific deletion of the Pik3r1 gene. These mice exhibited enhanced insulin and growth factor signaling and progressive changes in hepatic pathology, leading to the development of aggressive hepatocellular carcinomas with pulmonary metastases. Liver tumors that arose exhibited markedly elevated levels of phosphatidylinositol (3,4,5)-trisphosphate, along with Akt activation and decreased PTEN expression, at both the mRNA and protein levels. Together, these results substantiate the concept that the p85 subunit of PI3K has a tumor-suppressive role in the liver and possibly other tissues. Cancer Res; 70(13); 5305–15. ©2010 AACR.
Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury
Authors: Chia-Lung Wu, Deeptee Jain, Jenna N McNeill, Dianne Little, John A Anderson, Janet L Huebner, Virginia B Kraus, Ramona M Rodriguiz, William C Wetsel, Farshid Guilak
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background:</h3> Accurate identification of maternal deaths is paramount for audit and policy purposes. Our aim was to determine the accuracy and completeness of data on maternal deaths in hospital and those recorded on a death certificate, and the level of agreement between the 2 data sources. <h3>Methods:</h3> We conducted a retrospective population-based study using data for Ontario, Canada, from Apr. 1, 2002, to Dec. 31, 2015. We used Canadian Institute for Health Information (CIHI) databases to identify deaths during inpatient, emergency department and same-day surgery encounters. We captured Vital Statistics deaths in the Office of the Registrar General, Deaths (ORGD) data set. Deaths were considered within 42 days and within 365 days after a pregnancy outcome (live birth, miscarriage, ectopic pregnancy or induced abortion) for all multiple and singleton pregnancies. We calculated agreement statistics and 95% confidence intervals (CIs). <h3>Results:</h3> Among 1 679 455 live births and stillbirths, 398 pregnancy-related deaths in the ORGD data set were mapped to a birth in CIHI databases, and 77 (16.2%) were not. Among 2 039 849 recognized pregnancies, 534 pregnancy-related deaths in the ORGD data set were linked to CIHI records, and 68 (11.3%) were not. Among live births and stillbirths, after pregnancy-related deaths in the ORGD data set not matched to a maternal death in the CIHI databases were removed, concordance measures between CIHI and ORGD records for maternal death within 42 days after delivery included a κ value of 0.87 (95% CI 0.82–0.91) and positive percent agreement of 0.88 (95% CI 0.83–0.94). The corresponding measures were similar for maternal death within 42 days after the end of a recognized pregnancy. When unlinked pregnancy-related deaths in the ORGD data set were retained, agreement measures declined for death within 42 days after a live birth or stillbirth (κ = 0.68, 95% CI 0.62–0.74). For maternal death within 365 days after a live birth or stillbirth, or after the end of a recognized pregnancy, the concordance statistics were generally favourable when unlinked pregnancy-related deaths in the ORGD data set were removed but were substantially declined when they were retained. <h3>Interpretation:</h3> Maternal mortality cannot be ascertained solely with the use of hospital data, including beyond 42 days after the end of pregnancy. To improve linkage, we propose including health insurance numbers on provincial and territorial medical death certificates.
Advances in the Management of AIDS-Related Cytomegalovirus Retinitis
Authors: Henry Masur
Journal: Annals of Internal Medicine (1996)

Cytomegalovirus (CMV) retinitis, a common complication of the acquired immunodeficiency syndrome (AIDS), is increasing in frequency as patients infected with the human immunodeficiency virus (HIV) live longer.In recent years, the lifetime risk for CMV disease in HIV-infected persons has increased from 24.9% to 44.9%. Cytomegalovirus retinitis is usually diagnosed clinically: Almost all patients are CMV seropositive and have CD4+ counts less than 50 cells/mm3. Specific diagnostic tests that use antigen detection or quantitation of circulating nucleic acid to detect CMV are being developed, but they have not been validated for routine clinical use. Such tests would help predict disease, diagnose acute retinitis, and monitor therapy.
Sepsis: avoiding its deadly toll
Authors: Thomas Decker
Journal: Journal of Clinical Investigation (2004)

Systemic bacterial infection may culminate in a frequently fatal septic shock syndrome. The underlying pathology is the result of an uncontrolled inflammatory response, stimulated by the pathogen and its products. Toll-like receptors (TLRs) are critically involved in sensing bacteria and, in the case of sepsis, stimulate a pathogenic response by the innate immune system. A new study reports a successful attempt to inhibit systemic inflammation in mice by disrupting the formation of complexes between Gram-positive bacteria and their cognate receptor, TLR2.
457 EZETIMIBE IMPROVES EFFICACY OF PEGIFN AND RIBAVIRIN THERAPY VIA ACCELERATION OF IFN-MEDIATED ISG15 CONJUGATION SYSTEM
Authors: M. Nakamuta, M. Yada, K. Notsumata, N. Tanaka, R. Yada, M. Kohjima, K. Gotoh, T. Yoshimoto, N. Fukushima, K. Fukuizumi, K. Kawabe, T. Mizutani, N. Harada, S. Morizono, N. Sakamoto, M. Enjoji
Journal: Journal of Hepatology (2011)
Troponin T predicts in-hospital and 1-year mortality in patients with pulmonary embolism
Authors: K. M. Janata, J. M. Leitner, N. Holzer-Richling, A. Janata, A. N. Laggner, B. Jilma
Journal: European Respiratory Journal (2009)

We aimed to determine the prognostic value of troponin T (TNT) for in-hospital and 1-yr mortality in a large sample of patients with pulmonary embolism (PE). Patients presenting at the emergency department of a tertiary care centre from January 1998 to December 2006 with PE were included. A blood sample was taken at the time of presentation. To determine in-hospital and 1-yr mortality, data from the hospital records and the national death register were used. TNT was determined in 563 out of 737 patients with proven PE. TNT was elevated (&gt;0.03ng·mL −1 ) in 27%. In-hospital survival was 79% in TNT-positive patients compared with 94% in TNT-negative patients (p&lt;0.001). 1-yr survival was 71% in TNT-positive patients compared with 90% in TNT-negative patients (p&lt;0.001). Elevated TNT levels meant a four-times higher risk of in-hospital death and a three-times higher risk of 1-yr mortality, even after adjustment for the other most important risk factors of death in this population. Elevated TNT independently predicts in-hospital and 1-yr mortality in patients with acute PE.
Renal Manifestations in the Metabolic Syndrome
Authors: Francesco Locatelli, Pietro Pozzoni, Lucia Del Vecchio
Journal: Journal of the American Society of Nephrology (2006)

The metabolic syndrome, which is characterized by obesity, serum lipid profile alterations, hypertension, and fasting hyperglycemia, is very common in developed countries, and its prevalence is likely to increase. Chronic kidney disease (CKD) also has become a significant public health problem because it affects a considerable proportion of the adult population and is a major risk factor for cardiovascular disease and premature death. Although it is widely known that the metabolic syndrome is a major risk factor for the development of type 2 diabetes and cardiovascular disease, its precise relationship with the risk for renal impairment only recently has been clarified: Patients with the metabolic syndrome are at significantly higher risk for microalbuminuria and/or CKD, and the level of risk is related to the number of components of the syndrome itself. Although it is difficult to discriminate the detrimental renal effects of the metabolic syndrome from those of hypertension and impaired glucose metabolism, its other aspects (particularly obesity) may favor independently the development of renal abnormalities and may be considered new modifiable risk factors for CKD. These observations provide a rationale for intervention studies that aim to verify whether treating the many components of the metabolic syndrome can effectively prevent the development and progression of renal damage.
Percutaneous drainage of echinococcal cysts
Authors: H G SCHIPPER
Journal: Gut (2001)

Editor,—We read with interest the critical reply of Dr Morris (Gut 2000;47:156–7[OpenUrl][1][PubMed][2]) to the letter on the use of PAIR (puncture, aspiration, injection, reaspiration) in the treatment of echinococcal cysts. He questioned the safety and efficacy of PAIR and wondered whether there was any other place for PAIR than in situations where surgery was not available. We comment on the risk of sclerosing cholangitis. We agree with Dr Morris that injection of scolicidal agents into hydatid cysts is a potential risk for sclerosing cholangitis. However, this complication can be avoided when scolicidals are used for the correct indications. Scolicidals are not advocated at surgery because they have been associated with sclerosing cholangitis. The scolicidal probably enters pericystic liver tissue through breaks in the laminated … [1]: {openurl}?query=rft.jtitle%253DHepato-gastroenterology%26rft.stitle%253DHepatogastroenterology%26rft.aulast%253DCastellano%26rft.auinit1%253DG.%26rft.volume%253D41%26rft.issue%253D5%26rft.spage%253D458%26rft.epage%253D470%26rft.atitle%253DCaustic%2Bsclerosing%2Bcholangitis.%2BReport%2Bof%2Bfour%2Bcases%2Band%2Ba%2Bcumulative%2Breview%2Bof%2Bthe%2Bliterature.%26rft_id%253Dinfo%253Apmid%252F7851856%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=7851856&link_type=MED&atom=%2Fgutjnl%2F48%2F4%2F578.1.atom