tbuckley/cabot-search huggingface dataset:
Axial spondyloarthritis: a new disease entity, not necessarily early ankylosing spondylitis
Authors: Philip Cameron Robinson, Bryan Paul Wordsworth, John D Reveille, Matthew A Brown
Journal: Annals of the Rheumatic Diseases (2012)

New classification criteria for axial spondyloarthritis have been developed with the goal of increasing sensitivity of criteria for early inflammatory spondyloarthritis. However these criteria substantially increase heterogeneity of the resulting disease group, reducing their value in both research and clinical settings. Further research to establish criteria based on better knowledge of the natural history of non-radiographic axial spondyloarthritis, its aetiopathogenesis and response to treatment is required. In the meantime the modified New York criteria for ankylosing spondylitis remain a very useful classification criteria set, defining a relatively homogenous group of cases for clinical use and research studies.
STUDIES ON THYMUS FUNCTION
Authors: Osias Stutman, Edmond J. Yunis, Robert A. Good
Journal: The Journal of Experimental Medicine (1970)

Immunological restoration of 45-day old, neonatally thymectomized C3Hf mice by treatment with humoral thymic function (thymoma grafts, thymus or thymoma in diffusion chambers) ranges from 0 to 12% and is difficult to acheive. When small numbers (5–20 x 106) of young adult lymphohemopoietic cells, ineffective by themselves, are given in association with humoral thymic function, a cooperative effect is observed and restoration ranges from 30 to 60%. With a particular cell dosage (20 x 106), effectivity for cooperation with thymic function was the following in decreasing order: spleen, lymph nodes, thoracic duct cells, bone marrow, blood leukocytes, thymus, and Peyer's patch cells. Comparable results were obtained using spleen, thymus, and hemopoietic liver from newborn donors in association with thymic function. For similar cell dosages, newborn thymus cells were more effective than adult thymus in their cooperative effect with thymic function. Dispersed thymus cells in association with young adult bone marrow or newborn hemopoietic liver cells showed no synergism for the cooperative effect with thymic function in the present model. Using hemiallogeneic cells (F1 hybrid into parent) it was possible to show that restoration was mediated by proliferative expansion of the injected cells. This was indicated by specific tolerance to tissues of the other parental strain and by cellular chimerism, especially of lymphoid tissues, as indicated by chromosome markers and absence of significant numbers of immunocompetent cells of host origin. A population of paritally differentiated cells of hemopoietic origin, termed postthymic, sensitive to humoral activity of the thymus and present in the lymphohemopoietic tissues of adult and newborn mice is postulated to explain our results. These cells are postthymic and thymus dependent in the sense that they already received thymic influence, probably through traffic, and are incapable of self-renewal in absence of the thymus. Sensitivity to humoral activity of the thymus is characterized by proliferative expansion and/or a differentiative process eventually leading to larger numbers of competent cells.
Alcohol Consumption and Risk of Incident Rheumatoid Arthritis in Women: A Prospective Study
Authors: Bing Lu, Daniel H. Solomon, Karen H. Costenbader, Elizabeth W. Karlson
Journal: Arthritis & Rheumatology (2014)

To evaluate the association of alcohol consumption with the risk of rheumatoid arthritis (RA) in 2 large prospective cohorts, the Nurses' Health Study (NHS) and NHSII.
The Role of Fibroblasts in Complex Fractionated Electrograms During Persistent/Permanent Atrial Fibrillation
Authors: Takashi Ashihara, Ryo Haraguchi, Kazuo Nakazawa, Tsunetoyo Namba, Takanori Ikeda, Yuko Nakazawa, Tomoya Ozawa, Makoto Ito, Minoru Horie, Natalia A. Trayanova
Journal: Circulation Research (2011)

Rationale: Electrogram-based catheter ablation, targeting complex fractionated atrial electrograms (CFAEs), is empirically known to be effective in halting persistent/permanent atrial fibrillation (AF). However, the mechanisms underlying CFAEs and electrogram-based ablation remain unclear. Objective: Because atrial fibrosis is associated with persistent/permanent AF, we hypothesized that electrotonic interactions between atrial myocytes and fibroblasts play an important role in CFAE genesis and electrogram-based catheter ablation. Methods and Results: We used a human atrial tissue model in heart failure and simulated propagation and spiral wave reentry with and without regionally proliferated fibroblasts. Coupling of fibroblasts to atrial myocytes resulted in shorter action potential duration, slower conduction velocity, and lower excitability. Consequently, heterogeneous fibroblast proliferation in the myocardial sheet resulted in frequent spiral wave breakups, and the bipolar electrograms recorded at the fibroblast proliferation area exhibited CFAEs. The simulations demonstrated that ablation targeting such fibroblast-derived CFAEs terminated AF, resulting from the ablation site transiently pinning the spiral wave and then pushing it out of the fibroblast proliferation area. CFAEs could not be attributed to collagen accumulation alone. Conclusions: Fibroblast proliferation in atria might be responsible for the genesis of CFAEs during persistent/permanent AF. Our findings could contribute to better understanding of the mechanisms underlying CFAE-targeted AF ablation.
CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity
Authors: Satoshi Nishimura, Ichiro Manabe, Mika Nagasaki, Koji Eto, Hiroshi Yamashita, Mitsuru Ohsugi, Makoto Otsu, Kazuo Hara, Kohjiro Ueki, Seiryo Sugiura, Kotaro Yoshimura, Takashi Kadowaki, Ryozo Nagai
Journal: Nature Medicine (2009)
Effects of microwave radiation on brain energy metabolism and related mechanisms
Authors: Yan-Hui Hao, Li Zhao, Rui-Yun Peng
Journal: Military Medical Research (2015)

With the rapid development of electronic technologies, anxiety regarding the potential health hazards induced by microwave radiation (MW) has been growing in recent years. The brain is one of the most sensitive target organs for microwave radiation, where mitochondrial injury occurs earlier and more severely than in other organs. Energy metabolism disorders do play an important role during the process of microwave radiation-induced brain damage. In this paper, we will review the biological effects of microwave radiation, the features of brain energy supply and consumption and the effects of microwave radiation on mitochondrial energy metabolism and potential related mechanisms.
American Society of Clinical Oncology Statement: Toward Individualized Care for Patients With Advanced Cancer
Authors: Jeffrey M. Peppercorn, Thomas J. Smith, Paul R. Helft, David J. DeBono, Scott R. Berry, Dana S. Wollins, Daniel M. Hayes, Jamie H. Von Roenn, Lowell E. Schnipper
Journal: Journal of Clinical Oncology (2011)

Patients with advanced incurable cancer face complex physical, psychological, social, and spiritual consequences of disease and its treatment. Care for these patients should include an individualized assessment of the patient's needs, goals, and preferences throughout the course of illness. Consideration of disease-directed therapy, symptom management, and attention to quality of life are important aspects of quality cancer care. However, emerging evidence suggests that, too often, realistic conversations about prognosis, the potential benefits and limitations of disease-directed therapy, and the potential role of palliative care, either in conjunction with or as an alternative to disease-directed therapy, occur late in the course of illness or not at all. This article addresses the American Society of Clinical Oncology's (ASCO's) vision for improved communication with and decision making for patients with advanced cancer. This statement advocates an individualized approach to discussing and providing disease-directed and supportive care options for patients with advanced cancer throughout the continuum of care. Building on ASCO's prior statements on end-of-life care (1998) and palliative care (2009), this article reviews the evidence for improved patient care in advanced cancer when patients' individual goals and preferences for care are discussed. It outlines the goals for individualized care, barriers that currently limit realization of this vision, and possible strategies to overcome these barriers that can improve care consistent with the goals of our patients and evidence-based medical practice.
Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort
Authors: AS Walker, D Ford, CF Gilks, P Munderi, F Ssali, A Reid, E Katabira, H Grosskurth, P Mugyenyi, J Hakim, JH Darbyshire, DM Gibb, AG Babiker
Journal: The Lancet (2010)
Cholesterol Starvation Induces Differentiation of Human Leukemia HL-60 Cells
Authors: Carolina C. Sánchez-Martín, Alberto Dávalos, Covadonga Martín-Sánchez, Gema de la Peña, Carlos Fernández-Hernando, Miguel A. Lasunción
Journal: Cancer Research (2007)

Cholesterol metabolism is particularly active in malignant, proliferative cells, whereas cholesterol starvation has been shown to inhibit cell proliferation. Inhibition of enzymes involved in cholesterol biosynthesis at steps before the formation of 7-dehydrocholesterol has been shown to selectively affect cell cycle progression from G(2) phase in human promyelocytic HL-60 cells. In the present work, we explored whether cholesterol starvation by culture in cholesterol-free medium and treatment with different distal cholesterol biosynthesis inhibitors induces differentiation of HL-60 cells. Treatment with SKF 104976, an inhibitor of lanosterol 14-alpha demethylase, or with zaragozic acid, which inhibits squalene synthase, caused morphologic changes alongside respiratory burst activity and expression of cluster of differentiation antigen 11c (CD11c) but not cluster of differentiation antigen 14. These effects were comparable to those produced by all-trans retinoic acid, which induces HL-60 cells to differentiate following a granulocyte lineage. In contrast, they differed from those produced by vitamin D(3), which promotes monocyte differentiation. The specificity of the response was confirmed by addition of cholesterol to the culture medium. Treatment with PD 98059, an inhibitor of extracellular signal-regulated kinase, abolished both the activation of NADPH oxidase and the expression of the CD11c marker. In sharp contrast, BM 15766, which inhibits sterol Delta(7)-reductase, failed to induce differentiation or arrest cell proliferation. These results show that changes in the sterol composition may trigger a differentiation response and highlight the potential of cholesterol pathway inhibition as a possible tool for use in cancer therapy.
Attachment role of gonococcal pili. Optimum conditions and quantitation of adherence of isolated pili to human cells in vitro.
Authors: W A Pearce, T M Buchanan
Journal: Journal of Clinical Investigation (1978)

Gonoccocal pili facilitate attachment of virulent Neisseria gonorrhoeae to human cells. To characterize this attachment function, purified gonococcal pili isolated from four strains possessing antigenically distinct pili were radiolabeled with 125I and used to measure the attachment of pili to various human cells in vitro. Human buccal and cervical-vaginal mucosal epithealial cells, fallopian tube mucosa, and sperm bound pili in greater numbers per micrometer2 of surface area (1--10) than fetal tonsil fibroblasts, HeLa M cells, erythrocytes, or polymorphonuclear leukocytes. This cell specificity of attachment suggests a greater density of membrane pili binding sites on cells similar or identical to cells from natural sites of infection. The pili binding sites were quantitated as 1 X 10(4) per cervical-vaginal squamous cell. Pili of all antigenic types attached equally to a given cell type, implying that the attachment moiety of each pilus was similar. Attachement of gonoccocal pili to human cells occurred quickly with saturation of presumed receptor sites within 20--60 min. Attachment was temperature dependent (37 degrees greater than 20 degrees greater than 4 degrees C), and pH dependent (3.5 less than 4.5 less than 5.5 less than 7.5). Attachment was inhibited by antibody to pili (homologous pili Ab greater than heterologous Ab). The extent of possible protection against gonococcal infection due to inhibition of pili-mediated attachment might prove limited as a result of the considerable antigenic heterogeneity among pili and the observation that blockage of pili attachment is maximal only with antibody to pili of the infecting strain.
TCT-505 Prognostic Impact of Anaemia In Patients With ST Elevation Myocardial Infarction Treated By Primary PCI
Authors: Vrijraj Rathod, Daniel Jones, Krishnaraj Rathod, Daniel Bromage, Sean Gallagher, Ajay Jain, Charles Knight, Anthony Mathur, Martin Rothman, Adam Timmis, Rajiv Amersey, Andrew Wragg
Journal: Journal of the American College of Cardiology (2012)
High Frequency of <i>TP53</i> Mutation in <i>BRCA1</i> and Sporadic Basal-like Carcinomas but not in <i>BRCA1</i> Luminal Breast Tumors
Authors: Elodie Manié, Anne Vincent-Salomon, Jacqueline Lehmann-Che, Gaelle Pierron, Elisabeth Turpin, Mathilde Warcoin, Nadège Gruel, Ingrid Lebigot, Xavier Sastre-Garau, Rosette Lidereau, Audrey Remenieras, Jean Feunteun, Olivier Delattre, Hugues de Thé, Dominique Stoppa-Lyonnet, Marc-Henri Stern
Journal: Cancer Research (2009)

Abstract Breast tumors with a germ-line mutation of BRCA1 (BRCA1 tumors) and basal-like carcinoma (BLC) are associated with a high rate of TP53 mutation. Because BRCA1 tumors frequently display a basal-like phenotype, this study was designed to determine whether TP53 mutations are correlated with the hereditary BRCA1 mutated status or the particular phenotype of these tumors. The TP53 gene status was first investigated in a series of 35 BRCA1 BLCs using immunohistochemistry, direct sequencing of the coding sequence, and functional analysis of separated alleles in yeast, and compared with the TP53 status in a series of 38 sporadic (nonhereditary) BLCs. Using this sensitive approach, TP53 was found to be frequently mutated in both BRCA1 (34 of 35, 97%) and sporadic (35 of 38, 92%) BLCs. However, the spectrum of mutation was different, particularly with a higher rate of complex mutations, such as insertion/deletion, in BRCA1 BLCs than in the sporadic group [14 of 33 (42%) and 13 of 34 (9%), respectively; P = 0.002]. Secondly, the incidence of TP53 mutations was analyzed in 19 BRCA1 luminal tumors using the same strategy. Interestingly, only 10 of these 19 tumors were mutated (53%), a frequency similar to that found in grade-matched sporadic luminal tumors. In conclusion, TP53 mutation is highly recurrent in BLCs independently of BRCA1 status, but not a common feature of BRCA1 luminal tumors. [Cancer Res 2009;69(2):663–71]
Complex chronic comorbidities of COPD
Authors: L M Fabbri, F Luppi, B Beghé, K F Rabe
Journal: European Respiratory Journal (2007)

Chronic obstructive pulmonary disease (COPD) is defined by fixed airflow limitation associated with an abnormal pulmonary and systemic inflammatory response of the lungs to cigarette smoke. The systemic inflammation induced by smoking may also cause chronic heart failure, metabolic syndrome and other chronic diseases, which may contribute to the clinical manifestations and natural history of COPD. Thus COPD can no longer be considered a disease only of the lungs, as it is often associated with a wide variety of systemic consequences. A better understanding of the origin and consequences of systemic inflammation, and of potential therapies, will most likely lead to better care of patients with COPD. Medical textbooks and clinical guidelines still largely ignore the fact that COPD seldom occurs in isolation. As the diagnosis and assessment of severity of COPD may be greatly affected by the presence of comorbid conditions, the current authors believe that lung function measurement, noninvasive assessment of cardiovascular and metabolic functions, and circulating inflammatory markers ( e.g. C-reactive protein) might help to better characterise these patients. Similarly, preventive and therapeutic interventions should address the patient in their complexity.
Bleeding Risk in Very Old Patients on Vitamin K Antagonist Treatment
Authors: Daniela Poli, Emilia Antonucci, Sophie Testa, Alberto Tosetto, Walter Ageno, Gualtiero Palareti
Journal: Circulation (2011)

Vitamin K antagonist (VKA) therapy is increasingly being used for the prevention of venous thromboembolism and stroke in atrial fibrillation. Bleeds are the major concern for VKA prescription, especially in very old patients who carry many risk factors for bleeding. We performed a large multicenter prospective observational study that enrolled very old patients to evaluate the quality of anticoagulation and the incidence of bleedings.The study included 4093 patients ≥80 years of age who were naïve to VKA for thromboprophylaxis of atrial fibrillation or after venous thromboembolism. Patients' demographic and clinical data were collected, and the quality of anticoagulation and the incidence of bleeding were recorded. The follow-up was 9603 patient-years; median age at the beginning of follow-up was 84 years (range, 80 to 102 years). We recorded 179 major bleedings (rate, 1.87 per 100 patient-years), 26 fatal (rate, 0.27 per 100 patient-years). The rate of bleeding was higher in men compared with women (relative risk, 1.4; 95% confidence interval, 1.12 to 1.72; P=0.002) and among patients ≥85 years of age compared with younger patients (relative risk, 1.3; 95% confidence interval, 1.0 to 1.65; P=0.048). Time in therapeutic range was 62% (interquartile range, 49% to 75%). History of bleeding, active cancer, and history of falls were independently associated with bleeding risk in Cox regression analysis.In this large study on very old patients on VKA carefully monitored by anticoagulation clinics, the rate of bleedings was low, suggesting that age in itself should not be considered a contraindication to treatment. Adequate management of VKA therapy in specifically trained center allows very old and frail patients to benefit from VKA thromboprophylaxis.
Proper desensitization of CXCR4 is required for lymphocyte development and peripheral compartmentalization in mice
Authors: Karl Balabanian, Emilie Brotin, Vincent Biajoux, Laurence Bouchet-Delbos, Elodie Lainey, Odile Fenneteau, Dominique Bonnet, Laurence Fiette, Dominique Emilie, Françoise Bachelerie
Journal: Blood (2012)
Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma
Authors: Gordon W. Dewald, Terry Therneau, Dirk Larson, You Kyoung Lee, Stephanie Fink, Stephanie Smoley, Sarah Paternoster, Adewale Adeyinka, Rhett Ketterling, Daniel L. Van Dyke, Rafael Fonseca, Robert Kyle
Journal: Blood (2005)
Guanylyl Cyclase C–Induced Immunotherapeutic Responses Opposing Tumor Metastases Without Autoimmunity
Authors: Adam E. Snook, Benjamin J. Stafford, Peng Li, Gene Tan, Lan Huang, Ruth Birbe, Stephanie Schulz, Matthias J. Schnell, Mathew Thakur, Jay L. Rothstein, Laurence C. Eisenlohr, Scott A. Waldman
Journal: JNCI Journal of the National Cancer Institute (2008)

One of the greatest impediments to cancer immunotherapy is the paucity of antigens that are tumor specific, sufficiently immunogenic, and shared among patients. Mucosa-restricted antigens that are expressed by tumor cells represent a novel class of vaccine targets that are characterized by immunologic privilege, which limits systemic tolerance to those antigens, and immunologic partitioning, which shields mucosae from systemic autoimmune responses. Here we defined the immunogenicity and antitumor efficacy of guanylyl cyclase C (GCC), a protein that is normally restricted to intestinal mucosa and universally expressed by metastatic colorectal cancer.BALB/c mice (n = 197) were immunized with recombinant GCC-expressing viral vectors before (prophylactic) or after (therapeutic) a lethal challenge of GCC-expressing mouse colon cancer cells, and antitumor efficacy was monitored by quantifying metastasis and survival. Induction of autoimmunity was monitored by histopathology. Induction of GCC-specific B-cell and CD4(+) and CD8(+) T-cell responses were determined by enzyme-linked immunosorbent assay and ELISpot, respectively. Tolerance to GCC was quantified by comparing responses in GCC-deficient (n = 45) and wild-type (n = 69) C57BL/6 mice. Statistical tests were two-sided.Immunization with GCC-expressing viral vectors reduced the formation of metastases to liver (control vs GCC: mean = 30.4 vs 3.55 nodules, difference = 26.9 nodules, 95% confidence interval [CI] = 8.47 to 45.3 nodules; P = .008) and lung (control vs GCC: mean = 263 vs 55.7 nodules, difference = 207, 95% CI = 163 to 251; P < .001) and extended the median survival of mice with established lung metastases following therapeutic immunization (control vs GCC: 29 vs 38 days, P = .024), without autoimmunity. Antitumor efficacy reflected asymmetrical tolerance that was characterized by CD8(+) T-cell, but not CD4(+) T-cell or antibody, responses.Immunologic partitioning together with immunologic privilege highlight the potential of mucosa-restricted antigens, particularly GCC, as therapeutic targets for metastatic cancer.
90Yttrium PET/MR-Based Dosimetry After Liver Radioembolization (SIRT)
Authors: Michael Wissmeyer, Bénédicte M.A. Delattre, Habib Zaidi, Sylvain Terraz, Osman Ratib
Journal: Clinical Nuclear Medicine (2015)

Biodistribution and dosimetric aspects are important issues in the preparation realization of radionuclide therapies and thus play an emerging role in radioembolization of liver malignancies. Biodistribution assessment of liver selective internal radiotherapy (SIRT) has been shown feasible using PET/CT PET/magnetic resonance (MR). Whereas prospective dosimetry using 99mTc macroaggregated albumin SPECT/CT is discussed controversially, retrospective 90Y PET/CT has been shown feasible for dosimetry of SIRT in recent studies. Considering the advantages of PET/MR with regard to lesion detection radiation dose reduction compared to PET/CT, especially when repeated scanning is intended, we investigated the use of PET/MR for dosimetry of liver SIRT.