tbuckley/cabot-search huggingface dataset:
Validation of a prediction rule for development of rheumatoid arthritis in patients with early undifferentiated arthritis
Authors: B Kuriya, C K Cheng, H M Chen, V P Bykerk
Journal: Annals of the Rheumatic Diseases (2008)

To validate a model which predicts progression from undifferentiated arthritis (UA) to RA, in a Canadian UA cohort.The prediction rule, comprising variables which are scored from 0 to 13, with higher scores reflecting an increased risk of RA, was applied to baseline characteristics of all patients with UA. Progression to RA was determined at 6 months.105 patients were identified. By 6 months, 80 (76%) had developed RA while 25 (24%) had developed another diagnosis. Number of tender and swollen joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide positivity, poor functional status and high disease activity were associated with development of RA (p<0.01). Median prediction score was 8.0 for progressors, 5.0 for non-progressors. With these cut-off points, 18 (72%) patients with scores < or =5 did not develop RA, while 35 (97%) with scores > or =8 did develop RA.High scores in our cohort predicted those who progressed to RA by 6 months. Baseline scores > or =8 corresponded with higher rates of progression.
A neurobehavioral model of affiliative bonding: Implications for conceptualizing a human trait of affiliation
Authors: Richard A. Depue, Jeannine V. Morrone-Strupinsky
Journal: Behavioral and Brain Sciences (2005)

because little is known about the human trait of affiliation, we provide a novel neurobehavioral model of affiliative bonding. discussion is organized around processes of reward and memory formation that occur during approach and consummatory phases of affiliation. appetitive and consummatory reward processes are mediated independently by the activity of the ventral tegmental area (vta) dopamine (da)–nucleus accumbens shell (nas) pathway and the central corticolimbic projections of the u-opiate system of the medial basal arcuate nucleus, respectively, although these two projection systems functionally interact across time. we next explicate the manner in which da and glutamate interact in both the vta and nas to form incentive-encoded contextual memory ensembles that are predictive of reward derived from affiliative objects. affiliative stimuli, in particular, are incorporated within contextual ensembles predictive of affiliative reward via: (a) the binding of affiliative stimuli in the rostral circuit of the medial extended amygdala and subsequent transmission to the nas shell; (b) affiliative stimulus-induced opiate potentiation of da processes in the vta and nas; and (c) permissive or facilitatory effects of gonadal steroids, oxytocin (in interaction with da), and vasopressin on (i) sensory, perceptual, and attentional processing of affiliative stimuli and (ii) formation of social memories. among these various processes, we propose that the capacity to experience affiliative reward via opiate functioning has a disproportionate weight in determining individual differences in affiliation. we delineate sources of these individual differences, and provide the first human data that support an association between opiate functioning and variation in trait affiliation.
Donor Dopamine Pretreatment and Graft Function After Kidney Transplantation
Authors: Jonathan Ball
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mitogen-Activated Protein Kinase Phosphatase-1 Is a Mediator of Breast Cancer Chemoresistance
Authors: George W. Small, Yue Y. Shi, Linda S. Higgins, Robert Z. Orlowski
Journal: Cancer Research (2007)

The mitogen-activated protein kinase (MAPK) phosphatase (MKP)-1 is overexpressed in a large proportion of breast cancers, and in some systems interferes with chemotherapy-mediated proapoptotic signaling through c-Jun-NH(2)-terminal kinase (JNK). We therefore sought to examine whether MKP-1 is a mediator of breast cancer chemoresistance using A1N4-myc human mammary epithelial cells, and BT-474 and MDA-MB-231 breast carcinoma cells. Transient or stable overexpression of MKP-1 reduced caspase activation and DNA fragmentation while enhancing viability in the face of treatment with alkylating agents (mechlorethamine), anthracylines (doxorubicin), and microtubule inhibitors (paclitaxel). This overexpression was associated with suppression of JNK activation, and JNK blockade alone induced similar effects. In contrast, reduction of MKP-1 levels using a small interfering RNA, or its targeted inactivation, enhanced sensitivity to these drugs, and this was associated with increased JNK activity. Pharmacologic reduction of MKP-1 by pretreatment with a novel p38 MAPK inhibitor, SD-282, suppressed MKP-1 activation by mechlorethamine, enhanced active JNK levels, and increased alkylating agent-mediated apoptosis. Combination treatment with doxorubicin and mechlorethamine had similar effects, and the enhanced efficacy of this regimen was abolished by forced overexpression of MKP-1. These results suggest that the clinical efficacy of combinations of alkylating agents and anthracyclines are due to the ability of the latter to target MKP-1. Moreover, they support the hypothesis that MKP-1 is a significant mediator of breast cancer chemoresistance, and provide a rationale for development and translation of other agents targeting MKP-1 into the clinical arena to overcome resistance and induce chemosensitization.
The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein
Authors: Sandy K. Pang, Pi Jun Wang, Alfred Y. Chung, Allan W. Wolkoff
Journal: Hepatology (1998)

Oatp1, the organic anion transport polypeptide, is an integral membrane protein cloned from rat liver that mediates the uptake of various organic anions such as bromosulfophthalein (BSP) and taurocholate (TCA). Recent studies by others revealed that the thrombin inhibitor, CRC 220, a modified dipeptide, was transported by oatp1. The present study was designed to examine whether another modified peptide, enalapril, an angiotensin–converting enzyme inhibitor, was also a substrate. Transport was studied with enalapril (1 to 800 μmol/L, with [ 3 H]enalapril) in a HeLa cell line stably transfected with oatp1–cDNA under the regulation of a Zn 2+ –inducible promoter. Noninduced transfected cells (without zinc) that did not express oatp1 failed to take up enalapril. In contrast, cells expressing oatp1 transported enalapril, estrone sulfate (E 1 S), taurolithocholic acid sulfate (TLCAS), and the glutathione conjugate of BSP (BSPGSH). Uptake of enalapril by oatp1 at 37°C was substantially higher than that at 4°C. The rate at 37°C (uptake rates for induced – noninduced, transfected cells) was linear over 5 minutes and was concentration–dependent, characterized by a K m of 214 ± 67 μmol/L and a V max of 0.51 ± 0.15 nmol/min/mg protein. Enalapril uptake was inhibited competitively by BSP (at 1, 5, 10, and 50 μmol/L) and TCA (at 5, 25, and 100 μmol/L) with inhibition constants ( K i ) of 2 and 32 μmol/L, respectively. The metabolite enalaprilat was, however, not transported by oatp1. That oatp1 is not a general transporter of anionic compounds was further shown by the lack of transport of harmol sulfate, benzoate, and hippurate. These observations attest to the role of oatp1 as a specific transporter for at least two classes of pharmacologically important peptides.
The Use of a Neural Network to Detect Upper Airway Obstruction Caused by Goiter
Authors: PHILIP BRIGHT, MARTIN R. MILLER, JAYNE A. FRANKLYN, MICHAEL C. SHEPPARD
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Goiter is a common condition and can cause upper airway obstruction (UAO), which may be difficult to detect. We have studied maximal expiratory and inspiratory flow volume loops using a neural network to see if this offers a better way to identify patients with UAO. The flow-volume loops from 155 patients with goiter were assessed by a human expert and sorted into those with and without UAO. The reliability of this assessment was judged by using two observers who repeated the sorting 8 wk apart. A set of 46 patients with loops suggesting UAO and a set of 51 patients with normal flow loops were taken from these 155, and the loops from a further 50 subjects with airflow limitation caused by chronic obstructive pulmonary disease were used for training and testing the neural network. Novel and standard indices were derived from the loops and used by the neural network. The kappa score for agreement between each of the observers and the original classification were 0.5 and 0.46, respectively, with the agreement between the observers at each reading of 0.58 and 0.68. The neural network found that a combination of four novel scores for flatness of the expiratory loop, the moment ratio, and the FEV1/PEF ratio was best at identifying UAO with a kappa score of 0.81, a sensitivity of 88%, specificity of 94% and an accuracy of 92%. We conclude that a neural network using only six indices taken from the expiratory limb of a flow-volume loop was better than human experts at identifying flow loops with UAO.
Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis
Authors: Carole D. Mitnick, Sonya S. Shin, Kwonjune J. Seung, Michael L. Rich, Sidney S. Atwood, Jennifer J. Furin, Garrett M. Fitzmaurice, Felix A. Alcantara Viru, Sasha C. Appleton, Jaime N. Bayona, Cesar A. Bonilla, Katiuska Chalco, Sharon Choi, Molly F. Franke, Hamish S.F. Fraser, Dalia Guerra, Rocio M. Hurtado, Darius Jazayeri, Keith Joseph, Karim Llaro, Lorena Mestanza, Joia S. Mukherjee, Maribel Muñoz, Eda Palacios, Epifanio Sanchez, Alexander Sloutsky, Mercedes C. Becerra
Journal: New England Journal of Medicine (2008)

Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru.
Integrin Cytoplasmic Domain–Associated Protein-1 Attenuates Sprouting Angiogenesis
Authors: René Brütsch, Sven S. Liebler, Joycelyn Wüstehube, Arne Bartol, Stefanie E. Herberich, M. Gordian Adam, Anja Telzerow, Hellmut G. Augustin, Andreas Fischer
Journal: Circulation Research (2010)

Rationale: The ICAP1 (integrin cytoplasmic domain–associated protein-1) is a specific intracellular binding protein of β1-integrins and the cerebral cavernous malformation (CCM) protein CCM1. ICAP1 recruits CCM1 to the cell membrane and activates CCM1 by changing its conformation. Because CCM1 plays a critical role for cardiovascular development, we hypothesized that its activator ICAP1 is involved in vascular differentiation. Objective: The objective of this study was to define the role of ICAP1 in endothelial cells. Methods and Results: Loss of ICAP1 in primary human endothelial cells causes excessive angiogenic branching and network formation in vitro (3D sprouting angiogenesis) and in vivo (xenotransplantation of ICAP1-silenced human endothelial cells). ICAP1 increases cell motility and the initial formation of capillary sprouts but prevents vessel outgrowth. ICAP1 inhibits Rho kinase activity and ERK (extracellular signal-regulated kinase) phosphorylation and induces expression of the cell cycle inhibitors p21 and p27 , leading to less endothelial proliferation. However, ICAP1 promotes endothelial survival and AKT phosphorylation. Global gene expression analyses revealed that the ICAP1 effects are mediated by strong activation of DELTA-NOTCH signaling. Active NOTCH1 or silencing of the NOTCH ligand DLL4 phenocopy the ICAP1 effects and blockade of NOTCH cleavage rescues the ICAP1-mediated defects in endothelial cells. Both ICAP1 and NOTCH1 reduce the expression of ESM1 (endothelial cell–specific molecule-1), and silencing of ESM1 disturbs vascular endothelial growth factor– or fibroblast growth factor 2–induced sprouting angiogenesis. Conclusions: In this study, we identified ICAP1 as a novel regulator to prevent excessive sprouting angiogenesis.
Locoregional recurrence risk after lipofilling in breast cancer patients
Authors: J.Y. Petit, E. Botteri, V. Lohsiriwat, M. Rietjens, F. De Lorenzi, C. Garusi, F. Rossetto, S. Martella, A. Manconi, F. Bertolini, G. Curigliano, P. Veronesi, B. Santillo, N. Rotmensz
Journal: Annals of Oncology (2011)
Short Delay in Initiation of Radiotherapy May Not Affect Outcome of Patients With Glioblastoma: A Secondary Analysis From the Radiation Therapy Oncology Group Database
Authors: Deborah T. Blumenthal, Minhee Won, Minesh P. Mehta, Walter J. Curran, Luis Souhami, Jeff M. Michalski, C. Leland Rogers, Benjamin W. Corn
Journal: Journal of Clinical Oncology (2008)

Purpose To analyze the Radiation Therapy Oncology Group (RTOG) database of patients with glioblastoma and appraise whether outcome was influenced by time to initiation of radiation therapy (RT). Patients and Methods From 1974 through 2003, adult patients with histologically confirmed supratentorial glioblastoma were enrolled onto 16 RTOG studies. Of 3,052 enrolled patients, 197 patients (6%) were either initially rendered ineligible or had insufficient chronologic data, leaving a cohort of 2,855 patients for the present analysis. We selected four patient groups based on the interval from surgery to the start of RT: ≤ 2 weeks, 2 to 3 weeks, 3 to 4 weeks, more than 4 weeks to the protocol eligibility limit of 6 weeks. Survival times were estimated by the Kaplan-Meier method. Multivariate analysis incorporated variables of time interval, recursive partitioning analysis (RPA) class, and treatment regimen. Results No decrement in survival could be identified with increasing time to initiation of RT. Among our four temporal groupings, median survival time was unexpectedly and significantly greater in the group with the longest interval (&gt; 4 weeks) than in those with the shortest delay (≤ 2 weeks): respectively, 12.5 months versus 9.2 months (P &lt; .0001). On multivariate analysis, with overall survival as the end point, time interval more than 4 weeks and lower RPA class were both significant predictors of improved outcome. Treatment regimen was not a significant factor. Conclusion There is no evident reduction in survival by delaying initiation of RT within the relatively narrow constraint of 6 weeks. An unanticipated yet significantly superior outcome was identified for patients for whom RT was delayed beyond 4 weeks from surgery.
CD4+ T Cells Prevent Spontaneous Experimental Autoimmune Encephalomyelitis in Anti–Myelin Basic Protein T Cell Receptor Transgenic Mice
Authors: Fabienne Van de Keere, Susumu Tonegawa
Journal: The Journal of Experimental Medicine (1998)

Autoimmune diseases result from a failure of tolerance. Although many self-reactive T cells are present in animals and humans, their activation appears to be prevented normally by regulatory T cells. In this study, we show that regulatory CD4+ T cells do protect mice against the spontaneous occurrence of experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. Anti–myelin basic protein (MBP) TCR transgenic mice (T/R+) do not spontaneously develop EAE although many self-reactive T cells are present in their thymi and peripheral lymphoid organs. However, the disease develops in all crosses of T/R+ mice with recombination-activating gene (RAG)-1 knockout mice in which transgenic TCR-expressing cells are the only lymphocytes present (T/R− mice). In this study, crosses of T/R+ mice with mice deficient for B cells, CD8+ T cells, NK1.1 CD4+ T (NKT) cells, γ/δ T cells, or α/β T cells indicated that α/β CD4+ T cells were the only cell population capable of controlling the self-reactive T cells. To confirm the protective role of CD4+ T cells, we performed adoptive transfer experiments. CD4+ T cells purified from thymi or lymph nodes of normal mice prevented the occurrence of spontaneous EAE in T/R− mice. To achieve full protection, the cells had to be transferred before the recipient mice manifested any symptoms of the disease. Transfer of CD4+ T cells after the appearance of symptoms of EAE had no protective effect. These results indicate that at least some CD4+ T cells have a regulatory function that prevent the activation of self-reactive T cells.
Public Health Surveillance of Low-Frequency Populations
Authors: Elena M. Andresen, Paula H. Diehr, Douglas A. Luke
Journal: Annual Review of Public Health (2004)

Public health agencies often require data that address the needs of special populations, such as minority groups. Sources of surveillance data often contain insufficient numbers of subjects to fully inform health agencies. In this review, we address the problems of and potential approaches for situations with insufficient surveillance data. We use the examples of race and ethnic minority groups throughout our discussion. However, many of the broad issues are applicable to other special groups with low frequency or who are especially hard to reach. Our recommendations are based, in part, on a symposium held in Missouri with the collaboration of state health agency, community, and academic research participants. We review problems in using existing data and collecting new data, especially from nonprobability samples. We also describe fieldwork issues for reaching and collecting information from special populations. Decisions among methods and solutions may require seeking additional resources for surveillance.
Nitric oxide in the endometrium
Authors: I. Cameron
Journal: Human Reproduction Update (1998)

Nitric oxide (NO) is an important mediator of paracrine interactions, especially within the vascular system. It is a powerful inhibitor of platelet aggregation and a potent vasodilator. NO is also a neurotransmitter and it plays a role in cell-mediated cytotoxicity. NO-generating enzymes (nitric oxide synthases, NOS) have been described in the endometrium of a number of species, suggesting that NO might be involved in endometrial function. In human endometrium, endothelial NOS and inducible NOS have been localized to glandular epithelium in the non-pregnant uterus. Weak inducible NOS immunoreactivity has been observed in decidualized stromal cells. NO might participate in the initiation and control of menstrual bleeding. Furthermore, it may play a part in the inhibition of platelet aggregation within the endometrium, where menstrual haemostasis is thought to occur primarily by vasoconstriction rather than clot organization. Endometrially derived NO could also suppress myometrial contractility. Recent attention has focused on the part that NO might play in maintaining myometrial quiescence during pregnancy. NO also appears to relax the non-pregnant myometrium, an action which could be exploited for the medical treatment of primary dysmenorrhoea.
Pneumomediastinum secondary to use of a high speed air turbine drill during a dental extraction.
Authors: J Torres-Melero, J Arias-Diaz, J L Balibrea
Journal: Thorax (1996)

Pneumomediastinum and subcutaneous emphysema of the neck and thorax can occur exceptionally following a dental procedure. A case is described of acute subcutaneous emphysema of the lateral region of the neck and thorax associated with pneumomediastinum during a dental extraction with an air and water cooled turbine burn drill.
Asthma deaths and bronchodilator therapy
Authors: G Price
Journal: Thorax (2005)

▴ Anderson HR, Ayres JG, Sturdy PM, et al . Bronchodilator treatment and deaths from asthma: case-control study. BMJ2005;330:117–20 [OpenUrl][1][Abstract/FREE Full Text][2] This study concerning asthma deaths and bronchodilator therapy covered 33 health boards in the UK (27% of population) for 4 years from 1994 to 1998. Patients had asthma as the principal cause of death (at certification), were under the age of 65, with no other underlying non-respiratory cause. Data were gathered for the … [1]: {openurl}?query=rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.38316.729907.8F%26rft_id%253Dinfo%253Apmid%252F15618231%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/ijlink?linkType=ABST&journalCode=bmj&resid=330/7483/117&atom=%2Fthoraxjnl%2F60%2F5%2F413.atom
Actions of BAFF in B cell maturation and its effects on the development of autoimmune disease
Authors: F Melchers
Journal: Annals of the Rheumatic Diseases (2003)

BAFF, a member of the family of tumour necrosis factor (TNF) ligands, is essential for the development of peripheral mature, long lived B lymphocytes. It binds to three different receptors, BCMA, TACI, and BAFF-R, which are all members of the family of TNF receptors. Defects in the genes encoding BAFF or BAFF-R abolish the generation of mature B cells. BAFF is made by myeloid cells whereas BAFF-R is expressed preferentially on B cells. BAFF induces polyclonal maturation of resting, short lived immature B cells to resting, long lived mature B cells without proliferation. Lupus erythematodes prone mice have elevated blood levels of BAFF, and treatment of these mice with the BAFF decoy receptor (BCMA-Ig) prevents the onset of this systemic autoimmune disease. Human lupus patients also have elevated blood levels of BAFF. Treatment with BAFF neutralising agents (decoy receptors, monoclonal antibodies) should prevent, delay, or, at least, slow down the disease.