tbuckley/cabot-search huggingface dataset:
Contingency Management for the Treatment of Methamphetamine Use Disorders
Authors: John M Roll, Nancy M Petry, Maxine L Stitzer, Mary L Brecht, Jessica M Peirce, Michael J McCann, Jack Blaine, Marilyn MacDonald, Joan DiMaria, Leroy Lucero, Scott Kellogg
Journal: American Journal of Psychiatry (2006)

Theory and some preliminary evidence suggest that contingency management may be an effective treatment strategy or adjunct to psychosocial treatment for methamphetamine use disorders. An experimentally rigorous investigation on the topic was provided by a large multisite trial conducted under the auspices of the Clinical Trials Network of the National Institute on Drug Abuse.The authors report data on 113 participants who were diagnosed with methamphetamine abuse or dependence. They were randomly assigned to receive 12 weeks of either treatment as usual or treatment as usual plus contingency management. Urine samples were tested for illicit drugs, and breath samples were tested for alcohol. The reinforcers for drug-negative samples were plastic chips, some of which could be exchanged for prizes. The number of plastic chips drawn increased with each week of negative samples but was reset to one after a missed or positive sample.The participants in both groups remained in treatment for equivalent times, but those receiving contingency management in addition to usual treatment submitted significantly more negative samples, and they were abstinent for a longer period of time (5 versus 3 weeks).These results suggest that contingency management has promise as a component in treatment strategies for methamphetamine use disorder.
L-type Voltage-Gated Ca <sup>2+</sup> Channels Modulate Expression of Smooth Muscle Differentiation Marker Genes via a Rho Kinase/Myocardin/SRF–Dependent Mechanism
Authors: B.R. Wamhoff, D.K. Bowles, O.G. McDonald, S. Sinha, A.P. Somlyo, A.V. Somlyo, G.K. Owens
Journal: Circulation Research (2004)

Vascular smooth muscle cell (SMC) contraction is mediated in part by calcium influx through L-type voltage-gated Ca2+ channels (VGCC) and activation of the RhoA/Rho kinase (ROK) signaling cascade. We tested the hypothesis that Ca2+ influx through VGCCs regulates SMC differentiation marker expression and that these effects are dependent on RhoA/ROK signaling. Depolarization-induced activation of VGCCs resulted in a nifedipine-sensitive increase in endogenous smooth muscle myosin heavy chain (SMMHC) and SM alpha-actin expression and CArG-dependent promoter activity, as well as c-fos promoter activity. The ROK inhibitor, Y-27632, prevented depolarization-induced increase in SMMHC/SM alpha-actin but had no effect on c-fos expression. Conversely, the Ca2+/calmodulin-dependent kinase inhibitor, KN93, prevented depolarization-induced increases in c-fos expression with no effect on SMMHC/SM alpha-actin. Depolarization increased expression of myocardin, a coactivator of SRF that mediates CArG-dependent transcription of SMC marker gene promoters containing paired CArG cis regulatory elements (SMMHC/SM alpha-actin). Both nifedipine and Y-27632 prevented the depolarization-induced increase in myocardin expression. Moreover, short interfering RNA (siRNA) specific for myocardin attenuated depolarization-induced SMMHC/SM alpha-actin transcription. Chromatin immunoprecipitation (ChIP) assays revealed that depolarization increased SRF enrichment of the CArG regions in the SMMHC, SM alpha-actin, and c-fos promoters in intact chromatin. Whereas Y-27632 decreased basal and depolarization-induced SRF enrichment in the SMMHC/SM alpha-actin promoter regions, it had no effect of SRF enrichment of c-fos. Taken together, these results provide evidence for a novel mechanism whereby Ca2+ influx via VGCCs stimulates expression of SMC differentiation marker genes through mechanisms that are dependent on ROK, myocardin, and increased binding of SRF to CArG cis regulatory elements.
TGF-beta1 gene mutations in insulin-dependent diabetes mellitus and diabetic nephropathy.
Authors: F Pociot, P M Hansen, A E Karlsen, B L Langdahl, J Johannesen, J Nerup
Journal: Journal of the American Society of Nephrology (1998)

PCR assays were established for easy and fast analysis of two transforming growth factor-beta1 (TGF-beta1) gene mutations, a C to T transition at position 76 in exon 5 resulting in a change from threonine to isoleucine in position 263 (Thr263Ile) of the propeptide and a deletion of a C in the intron sequence eight bases prior to exon 5 (713-8delC). These mutations were evaluated in insulin-dependent diabetes mellitus (IDDM) patients (n = 137) and control subjects (n = 105) and in IDDM patients with (n = 170) and without (n = 99) nephropathy. After evaluating intra- and interindividual variation in TGF-beta1 expression levels, the TGF-beta1 mRNA level in phorbol 12-myristate-13-acetate-stimulated (1 ng/ml) lymphocytes from individuals with different TGF-beta1 genotypes was also studied. No association of the two TGF-beta1 sequence variations with IDDM in general was found. However, a weak but significant association of the Thr263Ile mutation with diabetic nephropathy was found (P = 0.03). No correlation between TGF-beta1 transcription level and genotype of any of the two studied polymorphisms was found. However, significant interindividual differences in TGF-beta1 mRNA levels were observed between the tested individuals (P < 0.0001) compatible with a genetic control mechanism of TGF-beta1 synthesis at the mRNA level.
Retinoic Acid Receptor-Beta as a Prognostic Indicator in Stage I Non–Small-Cell Lung Cancer
Authors: Fadlo R. Khuri, Reuben Lotan, Bonnie L. Kemp, Scott M. Lippman, Hong Wu, Lei Feng, J. Jack Lee, Catherine S. Cooksley, Bianca Parr, Evelyn Chang, Garrett L. Walsh, Jin S. Lee, Waun K. Hong, Xiao-Chun Xu
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Retinoids are pivotal in the growth and differentiation of certain epithelial tissues, interacting with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors. RAR-beta mRNA is undetectable by in situ hybridization (ISH) in 50% of non–small-cell lung cancers (NSCLC). RAR-β may suppress tumorigenicity. Therefore, we hypothesized that loss of expression of RAR-β gene in stage I NSCLC is a prognostic factor of a poor clinical outcome. PATIENTS AND METHODS: We retrospectively analyzed RAR-β mRNA levels (by ISH using a digoxigenin-labeled antisense riboprobe) in specimens from 185 consecutive patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available. RESULTS: One hundred fifty-six patients who met the criteria of pathologic stage I NSCLC and positivity for RXR-alpha mRNA (used as a control to assess RNA degradation) and who had adequate follow-up could be evaluated. RAR-β mRNA expression was undetectable in 51 patients, weakly positive in 64 patients, and strongly positive in 41 patients. Overall survival of the 41 patients with strongly positive RAR-β was significantly worse than for the 115 patients with weak or absent RAR-β (P = .045). CONCLUSION: Unexpectedly, strong RAR-β expression was associated with a significantly worse outcome of early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding should be further explored.
Prolonged Survival of Dendritic Cell–Vaccinated Melanoma Patients Correlates With Tumor-Specific Delayed Type IV Hypersensitivity Response and Reduction of Tumor Growth Factor β-Expressing T Cells
Authors: Mercedes N. López, Cristian Pereda, Gabriela Segal, Leonel Muñoz, Raquel Aguilera, Fermín E. González, Alejandro Escobar, Alexandra Ginesta, Diego Reyes, Rodrigo González, Ariadna Mendoza-Naranjo, Milton Larrondo, Alvaro Compán, Carlos Ferrada, Flavio Salazar-Onfray
Journal: Journal of Clinical Oncology (2009)

Purpose The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. Patients and Methods Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. Results The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) β+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P &lt; .0001). Conclusion Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFβ+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.
The route of priming influences the ability of respiratory virus–specific memory CD8+ T cells to be activated by residual antigen
Authors: Shiki Takamura, Alan D. Roberts, Dawn M. Jelley-Gibbs, Susan T. Wittmer, Jacob E. Kohlmeier, David L. Woodland
Journal: The Journal of Experimental Medicine (2010)

After respiratory virus infections, memory CD8+ T cells are maintained in the lung airways by a process of continual recruitment. Previous studies have suggested that this process is controlled, at least in the initial weeks after virus clearance, by residual antigen in the lung-draining mediastinal lymph nodes (MLNs). We used mouse models of influenza and parainfluenza virus infection to show that intranasally (i.n.) primed memory CD8+ T cells possess a unique ability to be reactivated by residual antigen in the MLN compared with intraperitoneally (i.p.) primed CD8+ T cells, resulting in the preferential recruitment of i.n.-primed memory CD8+ T cells to the lung airways. Furthermore, we demonstrate that the inability of i.p.-primed memory CD8+ T cells to access residual antigen can be corrected by a subsequent i.n. virus infection. Thus, two independent factors, initial CD8+ T cell priming in the MLN and prolonged presentation of residual antigen in the MLN, are required to maintain large numbers of antigen-specific memory CD8+ T cells in the lung airways.
A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension
Authors: Julie E. Goodwin, Junhui Zhang, David S. Geller
Journal: Journal of the American Society of Nephrology (2008)

Although glucocorticoid (GC)-induced hypertension has commonly been attributed to promiscuous activation of the mineralocorticoid receptor by cortisol, thereby promoting excess reabsorption of sodium and water, numerous lines of evidence indicate that this is not the only or perhaps even the primary mechanism. GC induce a number of effects on vascular smooth muscle (VSM) <i>in vitro</i> that may be pertinent to hypertension, but their contribution <i>in vivo</i> is unknown. To address this question, a mouse model with a tissue-specific knockout (KO) of the GC receptor in the VSM was created and characterized. Similar to control mice, KO mice exhibited normal baseline BP and, interestingly, showed normal circadian variation in BP. When dexamethasone was administered, however, the acute hypertensive response was markedly attenuated in KO mice, and there was a trend toward a decreased chronic hypertensive response. These data suggest that the GC receptor in VSM plays a critical role in the acute hypertensive response to GC <i>in vivo</i>.
Use of evidence based leaflets to promote informed choice in maternity care: randomised controlled trial in everyday practice
Authors: A O'Cathain
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the effect of leaflets on promoting informed choice in women using maternity services. <b>Design:</b> Cluster trial, with maternity units randomised to use leaflets (intervention units) or offer usual care (control units). Data collected through postal questionnaires. <b>Setting:</b> 13 maternity units in Wales. <b>Participants:</b> Four separate samples of women using maternity services. Antenatal samples: women reaching 28 weeks9 gestation before (n=1386) and after (n=1778) the intervention. Postnatal samples: women at eight weeks after delivery before (n=1741) and after (n=1547) the intervention. <b>Intervention:</b> Provision of 10 pairs of <i>Informed Choice</i> leaflets for service users and midwives and a training session for staff in their use. <b>Main outcome measures:</b> Change in the proportion of women who reported exercising informed choice. Secondary outcomes: changes in women9s knowledge; satisfaction with information, choice, and discussion; and possible consequences of informed choice. <b>Results:</b> There was no change in the proportion of women who reported that they exercised informed choice in the intervention units compared with the control units for either antenatal or postnatal women. There was a small increase in satisfaction with information in the antenatal samples in the intervention units compared with the control units (odds ratio 1.40, 95% confidence interval 1.05 to 1.88). Only three quarters of women in the intervention units reported being given at least one of the leaflets, indicating problems with the implementation of the intervention. <b>Conclusion:</b> In everyday practice, evidence based leaflets were not effective in promoting informed choice in women using maternity services.
ADP Stimulates Human Endothelial Cell Migration via P2Y <sub>1</sub> Nucleotide Receptor–Mediated Mitogen-Activated Protein Kinase Pathways
Authors: Jianzhong Shen, Paul E. DiCorleto
Journal: Circulation Research (2008)

Extensive research on the role of ADP in platelet activation led to the design of new anti-thrombotic drugs, such as clopidogrel (Plavix; sanofi-aventis); however, very little is known about the ADP-preferring nucleotide receptors (P2Y 1 , P2Y 12 , and P2Y 13 ) in endothelium. Here, we show that ADP stimulates migration of cultured human umbilical vein endothelial cells (HUVECs) in both Boyden chamber and in vitro wound repair assays. This promigratory effect was mimicked by 2-MeSADP, but not by AMP, and was inhibited by MRS2179 (P2Y 1 receptor antagonist) but not by AR-C69931MX (P2Y 12/13 receptor antagonist). RT-PCR revealed abundant P2Y 1 , barely detectable P2Y 12 , and absent P2Y 13 receptor message in these cells. In addition, both ADP and 2-MeSADP, but not AMP, activated the mitogen-activated protein kinase pathways as evidenced by increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), and p38 kinase. ADP also stimulated phosphorylation of p90RSK, a downstream substrate of phosphorylated ERK1/2, and induced phosphorylation of such transcription factors downstream of the JNK and p38 pathways as c-Jun and activating transcription factor-2. These signaling events were inhibited by MRS2179 but not by AR-C69931MX. Furthermore, blockade of the ERK or JNK pathways by U0126 and SP600125, respectively, abolished ADP- and 2-MeSADP–stimulated HUVEC migration. However, inhibition of the p38 pathway by SB203580 partially suppressed ADP- and 2-MeSADP–induced HUVEC migration. We conclude that ADP promotes human endothelial cell migration by activating P2Y 1 receptor–mediated MAPK pathways, possibly contributing to reendothelialization and angiogenesis after vascular injury.
Comparison of Rapid-Cycling and Non-Rapid-Cycling Bipolar Disorder Based on Prospective Mood Ratings in 539 Outpatients
Authors: Ralph W. Kupka, David A. Luckenbaugh, Robert M. Post, Trisha Suppes, Lori L. Altshuler, Paul E. Keck, Mark A. Frye, Kirk D. Denicoff, Heinz Grunze, Gabriele S. Leverich, Susan L. McElroy, Jörg Walden, Willem A. Nolen
Journal: American Journal of Psychiatry (2005)

To detect risk factors for rapid cycling in bipolar disorder, the authors compared characteristics of rapid-cycling and non-rapid-cycling patients both from a categorical and a dimensional perspective.Outpatients with bipolar I disorder (N=419), bipolar II disorder (N=104), and bipolar disorder not otherwise specified (N=16) were prospectively evaluated with daily mood ratings for 1 year. Subjects were classified as having rapid cycling (defined by the DSM-IV criterion of four or more manic or depressive episodes within 1 year) or not having rapid cycling, and the two groups' demographic and retrospective and prospective illness characteristics were compared. Associated factors were also evaluated in relationship to episode frequency.Patients with rapid cycling (N=206; 38.2%) significantly differed from those without rapid cycling (N=333) with respect to the following independent variables: history of childhood physical and/or sexual abuse, bipolar I disorder subtype, number of lifetime manic or depressive episodes, history of rapid cycling, and history of drug abuse. The prevalence of these characteristics increased progressively with episode frequency. The proportion of women was greater than the proportion of men only among patients with eight or more episodes per year. The average time spent manic/hypomanic increased as a function of episode frequency, but the average time spent depressed was comparable in patients with one episode and in those with more than one episode. Brief episodes were as frequent as full-duration DSM-IV-defined episodes.A number of heterogeneous risk factors were progressively associated with increasing episode frequency. Depression predominated in all bipolar disorder patients, but patients with rapid cycling were more likely to be characterized by manic features. The findings overall suggest that rapid cycling is a dimensional course specifier arbitrarily defined on a continuum of episode frequency.
Hemodynamic Alterations in Hemorrhagic Fever
Authors: GEORGE ENTWISLE, EDWARD HALE
Journal: Circulation (1957)

The cardiac output during the shock phase of hemorrhagic fever was very low. Increases in mean arterial pressure resulted from therapy with albumin or norepinephrine. With the former, this increase was associated with an increased cardiac output; with the latter, an increase in peripheral resistance. During the hypertensive phase, patients were found to have an increased cardiac output if they were also oliguric, and a relatively normal cardiac output if diuresis had begun. Some of the hypertensive patients presented the clinical syndrome of the "hyperdynamic state"; this occurred almost exclusively during the oliguric phase and was associated with high cardiac output and metabolic acidosis.
Chromatin Modification of the <i>Trefoil Factor 1</i> Gene in Human Breast Cancer Cells by the Ras/Mitogen-Activated Protein Kinase Pathway
Authors: Paula S. Espino, Lin Li, Shihua He, Jenny Yu, James R. Davie
Journal: Cancer Research (2006)

Abstract Histone H3 phosphorylation is a downstream response to activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. This modification is thought to have a role in chromatin remodeling and in the initiation of gene transcription. In MCF-7 breast cancer cells, we observed that phosphorylated histone H3 (phospho-H3) at Ser10 but not Ser28 increased with phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) treatment. Although phosphorylated extracellular signal-regulated kinase 1/2 levels in these cells cultured under estradiol deplete and replete conditions displayed no change, a significant induction was observed after TPA treatment. Furthermore, whereas both estradiol and TPA increased trefoil factor 1 (TFF1) mRNA levels in these cells, only TPA-induced and not estradiol-induced TFF1 expression was inhibited by the H3 kinase mitogen and stress activated protein kinase (MSK) inhibitor H89 and MAPK kinase inhibitor UO126, showing the involvement of the Ras/MAPK following TPA induction. Mutation of the activator protein 1 (AP-1) binding site abrogated the TPA-induced transcriptional response of the luciferase reporter gene under the control of the TFF1 promoter, showing the requirement for the AP-1 site. In chromatin immunoprecipitation assays, estradiol treatment resulted in the association of the estrogen receptor-α (ERα) and acetylated H3 with the TFF1 promoter. The levels of phospho-H3 and MSK1 associated with the TFF1 promoter were moderately increased. In the presence of TPA, whereas ERα was not bound to the promoter, a strong association of acetylated and/or phospho-H3, MSK1, and c-Jun was observed. These results show that although both stimuli lead to TFF1 gene activation, estradiol and TPA exert their effects on TFF1 gene expression by different mechanisms. (Cancer Res 2006; 66(9): 4610-6)
590 ASSESSMENT OF SYSTEMIC ENDOTHELIAL FUNCTION IN PATIENTS WITH CIRRHOSIS: COMPARISON BETWEEN PERIPHERAL ARTERIAL TONOMETRY (PAT) AND BRACHIAL ARTERY VASODILATATION BY ULTRASOUND (BAUS)
Authors: A. Berzigotti, S. Seijo, E. Reverter, J.G. Abraldes, J.C. García-Pagán, J. Bosch
Journal: Journal of Hepatology (2011)
Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000–01 FFCD/SFRO study
Authors: B. Chauffert, F. Mornex, F. Bonnetain, P. Rougier, C. Mariette, O. Bouché, J.F. Bosset, T. Aparicio, L. Mineur, A. Azzedine, P. Hammel, J. Butel, N. Stremsdoerfer, P. Maingon, L. Bedenne
Journal: Annals of Oncology (2008)
TAK1 is required for the survival of hematopoietic cells and hepatocytes in mice
Authors: Minghui Tang, Xudong Wei, Yinshi Guo, Peter Breslin, Shubin Zhang, Shanshan Zhang, Wei Wei, Zhenbiao Xia, Manuel Diaz, Shizuo Akira, Jiwang Zhang
Journal: The Journal of Experimental Medicine (2008)

Transforming growth factor β–activated kinase 1 (TAK1), a member of the MAPKKK family, is a key mediator of proinflammatory and stress signals. Activation of TAK1 by proinflammatory cytokines and T and B cell receptors induces the nuclear localization of nuclear factor κB (NF-κB) and the activation of c-Jun N-terminal kinase (JNK)/AP1 and P38, which play important roles in mediating inflammation, immune responses, T and B cell activation, and epithelial cell survival. Here, we report that TAK1 is critical for the survival of both hematopoietic cells and hepatocytes. Deletion of TAK1 results in bone marrow (BM) and liver failure in mice due to the massive apoptotic death of hematopoietic cells and hepatocytes. Hematopoietic stem cells and progenitors were among those hematopoietic cells affected by TAK1 deletion–induced cell death. This apoptotic cell death is autonomous, as demonstrated by reciprocal BM transplantation. Deletion of TAK1 resulted in the inactivation of both JNK and NF-κB signaling, as well as the down-regulation of expression of prosurvival genes.