tbuckley/cabot-search huggingface dataset:
The sense of conscious will
Authors: Gene M. Heyman
Journal: Behavioral and Brain Sciences (2004)

Wegner's conclusion that conscious will is an illusion follows from a key omission in his analysis. Although he describes conscious will as an experience, akin to one of the senses, he omits its objective correlate. The degree to which behavior can be influenced by its consequences (voluntariness) provides an objective correlate for conscious will. With conscious will anchored to voluntariness, the illusion disappears.
Primary breast non‐Hodgkin's lymphoma: A large single center study of initial characteristics, natural history, and prognostic factors
Authors: Patricia Validire, Mathieu Capovilla, Bernard Asselain, Youlia Kirova, Rémi Goudefroye, Corine Plancher, Alain Fourquet, Manuela Zanni, Philippe Gaulard, Anne Vincent‐Salomon, Didier Decaudin
Journal: American Journal of Hematology (2008)

Abstract The aims of this study were to define the initial pathological and clinical characteristics, and prognostic factors of patients with primary breast malignant lymphoma (PBL). All patients treated at the Institut Curie for lymphoma with breast involvement were reviewed. A pathological review of all cases was performed. Forty‐five cases were selected in whom 38 cases were of diffuse large B‐cell lymphoma. A complete analysis was then performed on these 38 patients. Twenty out of 28 cases (71%) of cases were Bcl‐2 positive and four out of 28 (14%) had a CD10 positive staining. Peculiar initial characteristics showed nodal involvement in 58% of the cases and two or more extra‐nodal sites in 31% of the cases. Among the 37 patients for whom all data were available, and according to the International Prognostic Index, 19 patients (51%) were classified in the low‐risk group, 5 cases (14%) in the low‐ to intermediate‐risk group, 6 patients (16%) in the intermediate‐ to high‐risk group, and 7 (19%) case in the high‐risk group. At the end of initial therapy, 34 patients (89%) achieved CR. With a median follow‐up of 96 months, 18 patients (47%) relapsed of whom 3 had a relapse in central nervous system site. The 5‐year disease‐free (DFS) and overall survivals (OS) were 54% and 61%, respectively. In multivariate analysis, the presence of 2 or more extranodal sites was prognostic for lower DFS ( P = 0.0008) and OS ( P = 0.09), and a performance status ≥1 was prognostic for lower OS ( P = 0.005). Finally, when our series was compared with a historical series of 111 patients with aggressive nodal lymphomas, we observed significant lower survival rates in localized PBL ( P &lt; 0.03). Initial breast localization has a pejorative impact on the outcome of patients with Non‐Hodgkin's Lymphoma (NHL), with an impressive adverse influence of additional extranodal sites. These results suggest a specific management of NHL with breast involvement. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.
Enhanced Dispersion of Repolarization and Refractoriness in Transgenic Mouse Hearts Promotes Reentrant Ventricular Tachycardia
Authors: Linda C. Baker, Barry London, Bum-Rak Choi, Gideon Koren, Guy Salama
Journal: Circulation Research (2000)

The heterogeneous distribution of ion channels in ventricular muscle gives rise to spatial variations in action potential (AP) duration (APD) and contributes to the repolarization sequence in healthy hearts. It has been proposed that enhanced dispersion of repolarization may underlie arrhythmias in diseases with markedly different causes. We engineered dominant negative transgenic mice that have prolonged QT intervals and arrhythmias due to the loss of a slowly inactivating K(+) current. Optical techniques are now applied to map APs and investigate the mechanisms underlying these arrhythmias. Hearts from transgenic and control mice were isolated, perfused, stained with di-4-ANEPPS, and paced at multiple sites to optically map APs, activation, and repolarization sequences at baseline and during arrhythmias. Transgenic hearts exhibited a 2-fold prolongation of APD, less shortening (8% versus 40%) of APDs with decreasing cycle length, altered restitution kinetics, and greater gradients of refractoriness from apex to base compared with control hearts. A premature impulse applied at the apex of transgenic hearts produced sustained reentrant ventricular tachycardia (n=14 of 15 hearts) that did not occur with stimulation at the base (n=8) or at any location in control hearts (n=12). In transgenic hearts, premature impulses initiated reentry by encountering functional lines of conduction block caused by enhanced dispersion of refractoriness. Reentrant VT had stable (>30 minutes) alternating long/short APDs associated with long/short cycle lengths and T wave alternans. Thus, optical mapping of genetically engineered mice may help elucidate some electrophysiological mechanisms that underlie arrhythmias and sudden death in human cardiac disorders.
Abstract 537: Sildenafil Suppresses Cardiac Hypertrophy through Inhibition of Canonical Transient Receptor Potential Cation Channel 6 Expression in Cardiac Myocytes
Authors: Norimichi Koitabashi, Manling Zhang, Eiki Takimoto, Takahiro Nagayama, David A Kass
Journal: Circulation (2007)

Background: We have shown that a phosphodiesterase 5A (PDE5A) inhibitor, sildenafil blocks cardiac pathological hypertrophy through inhibition of Gαq mediated signaling and calcineurin (Cn) signaling. However, the precise molecular mechanism is still unknown. Recently canonical transient receptor potential cation channel 6 (TRPC6) and its up-regulation have been shown to play a critical role for Gαq-mediated Cn activation in pathogenesis of cardiac hypertrophy. Therefore, we hypothesized that PDE5A inhibition blocks TRPC6 gene induction in cardiac myocytes and thus prevents cardiac hypertrophy. Methods and Results: We examined TRPC6 expression levels using real-time RT-PCR in hypertrophied mouse heart created by transverse aortic constriction (TAC). TRPC6 mRNA expression was significantly increased after TAC. Sildenafil effectively attenuated TAC-induced hypertrophy, Cn protein level and upregulation of TRPC6 mRNA. To investigate role of TRPC6 in sildenafil’s anti-hypertrophic effects, we studied cultured adult mouse cardiac myocytes (AMCM) and neonatal rat cardiac myocytes (NRCM). Stimulation with Endothelin 1 (ET1) or angiotensin II (AngII) increased cell surface area, leucine uptake, Cn protein expression and TRPC6 gene expression. Sildenafil dose-dependently blocked these increases. 8-bromo cGMP also blocked TRPC6 induction by ET1 and AngII. In addition, 8-bromo cGMP stimulation following adenovirus-mediated overexpression of cGMP-dependent protein kinase I-α (PKG) showed a marked decrease in TRPC6 expression. These results suggest that PKG activation regulates TRPC6 gene in cardiac myocytes. Using adenovirus-based expression of artificial PDE5A-gene silencing miRNA, PDE5 protein was effectively knocked down both in NRCM and AMCM. Importantly, PDE5-miRNA completely blocked ET1-mediated increase of Cn and TRPC6 same as sildenafil. Conclusion: Sildenafil effectively blocks TRPC6 induction both in vivo and in vitro . TRPC6 gene regulation is PKG and PDE5A dependent in cardiac myocytes. Given that TRPC6 induction triggers Gαq-mediated maladaptive signaling, especially Cn, these data show that the inhibition of TRPC6 gene expression contributes to the Gαq-coupled anti-hypertrophic mechanism of sildenafil.
The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-cell Lymphoma Project
Authors: J. Suzumiya, K. Ohshima, K. Tamura, K. Karube, N. Uike, K. Tobinai, R.D. Gascoyne, J.M. Vose, J.O. Armitage, D.D. Weisenburger
Journal: Annals of Oncology (2009)
Studies in Protein-Calorie Malnutrition
Authors: Joan L. Caddell
Journal: New England Journal of Medicine (1967)

MAGNESIUM deficiency has been demonstrated in protein-calorie malnutrition,1 , 2 but magnesium therapy is infrequently given. Some patients recover without it, and the potential dangers of magnesium have been emphasized. A double-blind clinical trial to assess magnesium therapy was conducted from June through December, 1964, in Nigerian children with severe malnutrition from the same clinic population as those studied in the first part of this paper.1 MethodPatient SelectionOnly children with histories and clinical findings compatible with magnesium deficiency were selected for the trial. All 52 children in the study had diarrhea for a month or more, and 21 had been . . .
Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-κB activation
Authors: S. Bondong, H. Kiefel, T. Hielscher, A.G. Zeimet, R. Zeillinger, D. Pils, E. Schuster, D.C. Castillo-Tong, I. Cadron, I. Vergote, I. Braicu, J. Sehouli, S. Mahner, M. Fogel, P. Altevogt
Journal: Annals of Oncology (2012)
IFN-Induced Transmembrane Protein 1 Promotes Invasion at Early Stage of Head and Neck Cancer Progression
Authors: Hiroko Hatano, Yasusei Kudo, Ikuko Ogawa, Takaaki Tsunematsu, Akira Kikuchi, Yoshimitsu Abiko, Takashi Takata
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Head and neck squamous cell carcinoma (HNSCC) shows persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. However, molecular mechanisms associated with invasion of HNSCC remain poorly understood. We identified IFN-induced transmembrane protein 1 (IFITM1) as a candidate gene for promoting the invasion of HNSCC by comparing the gene expression profiles between parent and a highly invasive clone. Therefore, we examined the role of IFITM1 in the invasion of HNSCC. Experimental Design: IFITM1 expression was examined in HNSCC cell lines and cases by reverse transcription–PCR and immunohistochemistry. IFITM1 overexpressing and knockdown cells were generated, and the invasiveness of these cells was examined by in vitro invasion assay. Gene expression profiling of HNSCC cells overexpressing IFITM1 versus control cells was examined by microarray. Results: HNSCC cells expressed IFITM1 mRNA at higher levels, whereas normal cells did not. By immunohistochemistry, IFITM1 expression was observed in early invasive HNSCC and invasive HNSCC. Interestingly, IFITM1 was expressed at the invasive front of early invasive HNSCC, and higher expression of IFITM1 was found in invasive HNSCC. In fact, IFITM1 overexpression promoted and IFITM1 knockdown suppressed the invasion of HNSCC cells in vitro. Gene expression profiling of HNSCC cells overexpressing IFITM1 versus control cells revealed that several genes, including matrix metalloproteinase, were up-regulated in IFITM1 overexpressing cells. Conclusion: Our findings suggest that IFITM1 plays an important role for the invasion at the early stage of HNSCC progression and that IFITM1 can be a therapeutic target for HNSCC.
Identification and Metastatic Potential of Tumor-Initiating Cells in Malignant Rhabdoid Tumor of the Kidney
Authors: Satohiko Yanagisawa, Ichiro Kadouchi, Kinji Yokomori, Masao Hirose, Michiyuki Hakozaki, Hiroshi Hojo, Kosaku Maeda, Eiji Kobayashi, Takashi Murakami
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Malignant rhabdoid tumor of the kidney (MRTK) is a rare and highly aggressive malignancy of infanthood. In an effort to delineate MRTK progression, we investigated the metastatic fate of some MRTK cells using xenotransplantation animal models and the tumor-initiating potential of CD133+ MRTK cells. Experimental Design: We established two MRTK cell lines (JMU-RTK-1 and JMU-RTK-2) from patients with MRTK. We generated five luciferase-expressing MRTK cells for in vivo luminescent imaging and evaluated the metastatic fate in an orthotopic xenotransplantation model. Capacities of MRTK-initiating cells were examined in nonobese diabetic/severe combined immunodeficient mice after antibody-mediated magnetic bead sorting. Use of chemokine receptor CXCR4 expression as a metastatic marker was evaluated by flow cytometry and Western blotting. Results: MRTK cell lines showed distant organ metastasis. JMU-RTK-1, JMU-RTK-2, and G401 cells showed considerable aggressiveness compared with SWT-1 and SWT-2 cells (P &amp;lt; 0.05). Moreover, as few as 1,000 CD133+ MRTK cells initiated tumor development in nonobese diabetic/severe combined immunodeficient mice by 21 days (60-100%) in all examined cell lines, although the same number of CD133− MRTK cells could not form tumors (0%). Interestingly, the metastatic potential of the CD133+ population remained unaffected compared with a nonenriched population. The potential metastatic marker CXCR4 was expressed in CD133+ and CD133− MRTK cells, and CD133− cells seemed to play a cooperative role in terms of tumorigenicity and metastasis. Conclusions: These results suggest that CD133+ cells may determine the metastatic fate of MRTK cells and that CD133− cells may play an auxiliary role in tumor progression and metastasis.
SOCIAL MARKETING IN PUBLIC HEALTH
Authors: Sonya Grier, Carol A. Bryant
Journal: Annual Review of Public Health (2004)

▪ Abstract Social marketing, the use of marketing to design and implement programs to promote socially beneficial behavior change, has grown in popularity and usage within the public health community. Despite this growth, many public health professionals have an incomplete understanding of the field. To advance current knowledge, we provide a practical definition and discuss the conceptual underpinnings of social marketing. We then describe several case studies to illustrate social marketing's application in public health and discuss challenges that inhibit the effective and efficient use of social marketing in public health. Finally, we reflect on future developments in the field. Our aim is practical: to enhance public health professionals' knowledge of the key elements of social marketing and how social marketing may be used to plan public health interventions.
In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins.
Authors: G F Pierce, T A Mustoe, R M Senior, J Reed, G L Griffin, A Thomason, T F Deuel
Journal: The Journal of Experimental Medicine (1988)

Human platelet-derived growth factor (hPDGF) is likely to be important in stimulating tissue repair, based upon its in vivo chemotactic and stimulatory activities for inflammatory cells and fibroblasts and upon the presence of PDGF and related proteins in platelets, macrophages, and activated fibroblasts, cell types that make up the milieu of the healing wound. Recombinant human c-sis (rPDGF-B), homodimers of the B chain of PDGF, were compared with hPDGF in vitro. rPDGF-B was immunologically similar to hPDGF and, at identical concentrations, similar to hPDGF in stimulating fibroblast mitogenesis and chemotaxis of polymorphonuclear leukocytes, monocytes, and fibroblasts. Purified hPDGF and rPDGF-B were also tested in vivo for potency in a model of tissue repair using a linear incision wound through rat dermis. A single application of hPDGF or rPDGF-B (2-20 micrograms/wound) in a slow release vehicle at the time of wounding resulted in a dose-dependent, statistically highly significant increase of breaking strength of treated wounds. Wound healing in animals treated with rPDGF-B was 170% stronger and accelerated by 2 d during the first week over control wounds and by 4-6 d over the next 2 wk. Histologic evaluation of growth factor-treated wounds correlated the in vitro chemotactic activity and the accelerated healing of wounds with a striking inflammatory cell infiltrate early after wounding, markedly increased formation of granulation tissue by 4-d, and increased fibrosis by 14 d in comparison to control wounds. The results thus demonstrate that rPDGF-B is fully active in in vitro tests of mitogenesis and chemotaxis and, for the first time, demonstrate directly that PDGF significantly advances wound healing in incisional wounds of experimental animals.
The results of ileorectal anastomosis at St Mark's Hospital from 1953 to 1968
Authors: W. N. W. Baker
Journal: Gut (1970)

The popular view of ileorectal anastomosis for ulcerative colitis as an operation of above average mortality and morbidity is supported by the results of this series. Great care must be taken to differentiate ulcerative colitis from Crohn's disease of the colon, as it is clear from consideration of their clinical course that they are different disease entities with a different prognosis. It is suggested that the more general adoption of Aylett's operative technique would reduce the number of failures due to sepsis. There appears to be a group of patients, 15% in this series, who will be failures because of intractable diarrhoea despite a technically adequate and successful operation, but it might be possible to reduce these with modern medical therapy given postoperatively.Patients with a preoperative history of more than 10 years' disease appear to do better than the others. An actively diseased rectum does not appear adversely to affect the result, and the fulminating disease is not a counter indication to a staged ileorectal anastomosis. The use of steroids preoperatively does not appear to affect the healing of the anastomosis or the longterm result of the operation. No case of carcinoma of the rectum has occurred in this series but there has been histological evidence of premalignant change in two patients. The need for a strict follow-up programme, including regular sigmoidoscopy and rectal biopsy, is emphasized.
Chronic Restraint Stress Promotes Lymphocyte Apoptosis by Modulating Cd95 Expression
Authors: Deling Yin, David Tuthill, R. Allan Mufson, Yufang Shi
Journal: The Journal of Experimental Medicine (2000)

Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it is well established that stress alters the release of various hormones and neurotransmitters, the mechanisms by which stress affects immune responses remain elusive. We report here that mice subjected to chronic 12-hour daily physical restraint for two days exhibited a significant reduction in splenocytes, a process likely mediated by apoptosis as demonstrated by the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling assay. CD95 (Fas/APO-1) expression in splenic lymphocytes of stressed mice was substantially increased. Interestingly, Fas-immunoglobulin fusion protein and blocking antibodies against CD95 ligand inhibit stress-induced reduction in lymphocytes. The stress-induced changes in CD95 expression and lymphocyte number could be blocked by naltrexone or naloxone, specific opioid receptor antagonists, indicating a pivotal role of endogenous opioids in this process. In addition, the reduction of splenocytes in this model system seems to be independent of the hypothalamo-pituitary-adrenal axis, as both adrenalectomized and sham-operated mice exhibited similar responses to chronic stress. Moreover, chronic physical restraint failed to induce a decrease in lymphocyte numbers in CD95-deficient (Faslpr/lpr) mice. Therefore, stress modulates the immune system through CD95-mediated apoptosis dependent on endogenous opioids.
Critical role of c-jun (NH2) terminal kinase in paracetamol- induced acute liver failure
Authors: N. C Henderson, K. J Pollock, J. Frew, A. C Mackinnon, R. A Flavell, R. J Davis, T. Sethi, K. J Simpson
Journal: Gut (2006)

<b>Background:</b> Acute hepatic failure secondary to paracetamol poisoning is associated with high mortality. C-jun (NH2) terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and is a key intracellular signalling molecule involved in controlling the fate of cells. <b>Aim:</b> To examine the role of JNK in paracetamol-induced acute liver failure (ALF). <b>Methods:</b> A previously developed mouse model of paracetamol poisoning was used to examine the role of JNK in paracetamol-induced ALF. <b>Results:</b> Paracetamol-induced hepatic JNK activation both in human and murine paracetamol hepatotoxicity and in our murine model preceded the onset of hepatocyte death. JNK inhibition in vivo (using two JNK inhibitors with different mechanisms of action) markedly reduced mortality in murine paracetamol hepatotoxicity, with a significant reduction in hepatic necrosis and apoptosis. In addition, delayed administration of the JNK inhibitor was more effective than <i>N</i>-acetylcysteine after paracetamol poisoning in mice. JNK inhibition was not protective in acute carbon tetrachloride-mediated or anti-Fas antibody-mediated hepatic injury, suggesting specificity for the role of JNK in paracetamol hepatotoxicity. Furthermore, disruption of the <i>JNK1</i> or <i>JNK2</i> genes did not protect against paracetamol-induced hepatic damage. Pharmacological JNK inhibition had no effect on paracetamol metabolism, but markedly inhibited hepatic tumour necrosis foctor α (TNF α) production after paracetamol poisoning. <b>Conclusions:</b> These data demonstrated a central role for JNK in the pathogenesis of paracetamol-induced liver failure, thereby identifying JNK as an important therapeutic target in the treatment of paracetamol hepatotoxicity.
Results of Whole-Brain Radiation As Salvage of Methotrexate Failure for Immunocompetent Patients With Primary CNS Lymphoma
Authors: Paul L. Nguyen, Arnab Chakravarti, Dianne M. Finkelstein, Fred H. Hochberg, Tracy T. Batchelor, Jay S. Loeffler
Journal: Journal of Clinical Oncology (2005)

This study evaluates the efficacy and toxicity of whole-brain radiation therapy (WBRT) as salvage therapy for immunocompetent patients who failed initial high-dose methotrexate for primary CNS lymphoma (PCNSL).The study cohort included 27 consecutive patients who failed initial high-dose methotrexate and then received salvage WBRT (median dose, 36 Gy). Actuarial survival was measured from the initiation of radiotherapy.Ten patients (37%) achieved a complete radiographic response (CR), and 10 patients (37%) a partial response to WBRT, for a 74% overall radiographic response rate. At the time of maximal response, Karnofsky performance status improved in 12 (44%) of 27 patients and at least stabilized in 67%. Median estimated survival from initiation of WBRT was 10.9 months (range, 0.3 to 63.7 months). The univariate predictor of longer survival was age less than 60 years at the time of WBRT (P = .028). Among patients who survived 4 months, achievement of a CR to WBRT by 4 months (P = .002) predicted longer survival. Late treatment-associated neurotoxicity was diagnosed in four patients (15%) and was significantly associated with total radiation doses greater than 36 Gy (P = .04). No patient treated with daily fractions less than 1.8 Gy developed late neurotoxicity.For patients with PCNSL who experience treatment failure with methotrexate, WBRT provides high response rates (74%) and a median survival of 10.9 months. Age less than 60 years and response to WBRT predict post-WBRT survival. Modest rates of late neurotoxicity (15%) were seen and were associated with a total dose greater than 36 Gy.