tbuckley/cabot-search huggingface dataset:
B7 and interleukin 12 cooperate for proliferation and interferon gamma production by mouse T helper clones that are unresponsive to B7 costimulation.
Authors: E E Murphy, G Terres, S E Macatonia, C S Hsieh, J Mattson, L Lanier, M Wysocka, G Trinchieri, K Murphy, A O'Garra
Journal: The Journal of Experimental Medicine (1994)

We have previously shown that dendritic cells isolated after overnight culture, which can express B7 and are potent stimulators of naive T cell proliferation, are relatively poor at inducing the proliferation of a panel of murine T helper 1 (Th1) clones. Maximal stimulation of Th1 clones was achieved using unseparated splenic antigen presenting cells (APC). An explanation for these findings is provided in the present study where we show that FcR+ L cells transfected with B7 stimulate minimal proliferation of Th1 clones in response to anti-CD3 antibodies, in contrast to induction of significant proliferation of naive T cells. However, addition of interleukin 12 (IL-12) to cultures of Th1 cells stimulated with anti-CD3 and FcR+ B7 transfectants resulted in a very pronounced increase in proliferation and interferon gamma (IFN-gamma) production. Exogenous IL-12 did not affect the B7-induced proliferation of naive T cells. This showed that whereas costimulatory signals delivered via B7-CD28 interaction are sufficient to induce significant proliferation of naive T cells activated through occupancy of the T cell receptor, Th1 T cell clones require cooperative costimulation by B7 and IL-12. This costimulation was shown to be specific by inhibition of proliferation and IFN-gamma production using chimeric soluble cytolytic T lymphocyte-associated antigen 4-human IgG1Fc (CTLA4-Ig) and anti-IL-12 antibodies. Furthermore, the significant antigen specific proliferation and IFN-gamma production by Th1 clones observed when splenocytes were used as APC was almost completely abrogated using CTLA4-Ig and anti-IL-12 antibodies. Thus two costimulatory signals, B7 and IL-12, account for the ability of splenic APC to induce maximal stimulation of Th1 clones. IL-10 downregulates the expression of IL-12 by IFN-gamma-stimulated macrophages and this may account largely for t the ability of IL-10 to inhibit APC function of splenic and macrophage APC for the induction of Th1 cell proliferation and IFN-gamma production. Indeed we show that IL-12 can overcome the inhibitory effect of IL-10 for the APC-dependent induction of proliferation and IFN-gamma production by Th1 clones. These results suggest that proliferation by terminally differentiated Th1 clones, in contrast to naive T cells, requires stimulation via membrane-bound B7 and a cytokine, IL-12. It is possible that these signals may result in the activation of unresponsive T cells during an inflammatory response. IL-10, by its role in regulating such innate inflammatory responses, may thus help to maintain these T cells in an unresponsive state.
Effect of azodisal sodium and sulphasalazine on ileostomy output of fluid and PGE2 and PGF2 alpha in subjects with a permanent ileostomy.
Authors: H Sandberg-Gertzen, G Jarnerot, K Bukhave, K Lauritsen, J Rask-Madsen
Journal: Gut (1986)

Azodisal sodium is a highly effective means of oral delivery of 5-amino-salicylic acid to the colonic mucosa. Administration of this drug to patients intolerant of sulphasalazine, however, occasionally results in liquid stools. In preliminary experiments, which comprised 10 healthy volunteers treated with colectomy for ulcerative colitis, ileostomy fluid output increased (p less than 0.001) during oral intake of azodisal sodium (1 g/day). In a double blind, placebo controlled crossover study, comprising eight similar volunteers, ileostomy fluid output increased (p less than 0.05) in a dose related manner during intake of azodisal sodium (1 g/day vs 2 g/day) compared with placebo or sulphasalazine (2 g/day). Concentrations of prostaglandin (PG)F2 alpha in free ileal water determined by equilibrium in vivo dialysis of ileostomy contents decreased (p less than 0.05) during intake of azodisal sodium (2 g/day), whereas concentrations of PGE2 and the output of PGE2, PGF2 alpha, and 'PGE2 + PGF2 alpha' remained unchanged. Thus increased formation of PGs is apparently not the cause of increased ileostomy fluid output associated with azodisalicylate intake.
The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi
Authors: S. Luminari, I. Biasoli, L. Arcaini, A. Versari, C. Rusconi, F. Merli, M. Spina, A.J.M. Ferreri, P.L. Zinzani, A. Gallamini, S. Mastronardi, C. Boccomini, G. Gaidano, A.M. D'Arco, F. Di Raimondo, A.M. Carella, A. Santoro, P. Musto, M. Federico
Journal: Annals of Oncology (2013)
Partners in Care? Hospices and Health Authorities
Authors: T O'Brien
Journal: BMJ (1994)

David Clark Avebury, £32, pp 155 ISBN 1-85628-277-9

David Clark's research based text is a valuable addition to published studies on hospice and palliative care. It is particularly welcome at a time when hospice services have become increasingly diversified, with the development of community based services, day care facilities, and specialist support services within general hospitals. In addition, service provision must now be viewed in the context of a purchaser-provider market.

Written primarily from a sociological perspective and based on a frank and detailed …
Whole-Body Optical Imaging in Animal Models to Assess Cancer Development and Progression
Authors: Eric L. Kaijzel, Gabri van der Pluijm, Clemens W.G.M. Löwik
Journal: Clinical Cancer Research (2007)

Abstract Different optical-based imaging models were used to investigate tumor progression and metastasis with particular emphasis on metastasis to bone and bone marrow. We describe how optical imaging can be used to follow important processes in tumor development and treatment response, including angiogenesis, apoptosis, and proteolysis. Finally, we discuss the translation of one optical imaging modality, near-IR fluorescence, from animal validation studies to applications in the clinic related to cancer management.
Holt–Oram Syndrome and Atrial Fibrillation
Authors: Elisabetta Cerbai, Laura Sartiani
Journal: Circulation Research (2008)

C ardiogenesis is a complex phenomenon: its success- and ultimately life births-depends on factors acting in a combinatorial or hierarchical fashion and turning on and off gene transcription.Actually, the incidence of cardiac defects at birth is relatively high (1% to 2%), and our comprehension of these phenomena very limited.Hence, the role of transcription factors in cardiac specification and maturation has claimed increasing attention in recent years, providing a complex and evolving picture of the molecular and cellular processes involved but leaving many questions unanswered.In this issue of Circulation Research, Postma et al 1 add to a growing list of regulatory factors/functions a step forward in our understanding of cardiac morphogenesis and disclosing novel features of Tbx5.
Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison
Authors: I. S. T. Bos, R. Gosens, A. B. Zuidhof, D. Schaafsma, A. J. Halayko, H. Meurs, J. Zaagsma
Journal: European Respiratory Journal (2007)

Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide. Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia. This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.
Interleukin 4–induced gene 1 is activated in primary mediastinal large B-cell lymphoma
Authors: Christiane Copie-Bergman, Marie-Laure Boulland, Catherine Dehoulle, Peter Möller, Jean-Pierre Farcet, Martin J. S. Dyer, Corinne Haioun, Paul-Henri Roméo, Philippe Gaulard, Karen Leroy
Journal: Blood (2003)
Long-term Instability of Fasting Plasma Glucose, a Novel Predictor of Cardiovascular Mortality in Elderly Patients With Non–Insulin-Dependent Diabetes Mellitus
Authors: M. Muggeo, G. Verlato, E. Bonora, G. Zoppini, M. Corbellini, R. de Marco
Journal: Circulation (1997)

We recently reported that long-term fasting plasma glucose (FPG) instability predicts all-cause mortality in elderly patients with non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to evaluate whether glucose instability, as represented by the coefficient of variation of FPG concentrations (CV-FPG) measured during a 3-year period, can predict specific causes of death in the subsequent 5 years.Five hundred sixty-six elderly patients with NIDDM were followed up for 5 years to assess mortality and causes of death. All FPG determinations of the 3 years preceding the follow-up available in the clinical records were collected and analyzed. Patients were grouped in tertiles of mean FPG, CV-FPG, and the slope of FPG. These parameters of glucose control, as well as sex, age, duration of diabetes, insulin treatment, cigarette smoking, hypertension, and total cholesterol, were included in a multivariate analysis of mortality. During the follow-up, 63 men and 128 women died. Diabetes- and malignancy-related mortality were not independently associated with any parameter of glucose control, whereas cardiovascular-related mortality was independently associated with CV-FPG (P=.007) but not with the mean or the slope of FPG. In particular, the relative risk of cardiovascular mortality in subjects in tertile III versus tertile I of CV-FPG was 2.40 (95% CI, 1.28 to 4.53).These results indicate that FPG instability is a predictor of cardiovascular-related mortality in elderly patients with NIDDM and suggest that glucose stability might be a goal in the management of these patients.
High expression of neuroguidin increases the sensitivity of acute myeloid leukemia cells to chemotherapeutic drugs
Authors: Kejun Chen, Shuqing Lü, Hui Cheng, Gusheng Tang, Min Liu, Hong Zhou, Jianmin Wang
Journal: Journal of Hematology & Oncology (2015)

Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein. The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells. Proliferation inhibition and apoptosis in NGDN over-expressing myeloid multidrug-resistant leukemia cells (K562/A02-NGDN) was significantly higher than in control K562/A02 cells following treatment with vincristine, etoposide, and epirubicin, indicating that NGDN over-expression can increase the sensitivity of multidrug-resistant leukemia cells to chemotherapeutic drugs. Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.
Effect of Communication Skills Training Program for Oncologists Based on Patient Preferences for Communication When Receiving Bad News: A Randomized Controlled Trial
Authors: Maiko Fujimori, Yuki Shirai, Mariko Asai, Kaoru Kubota, Noriyuki Katsumata, Yosuke Uchitomi
Journal: Journal of Clinical Oncology (2014)

The aim of this study was to identify the effects of a communication skills training (CST) program for oncologists, developed based on patient preferences regarding oncologists' communication.Thirty oncologists were randomly assigned to either an intervention group (IG; 2-day CST workshop) or control group (CG). Participants were assessed on their communication performance during simulated consultation and their confidence in communicating with patients at baseline and follow-up. A total of 1,192 patients (response rate, 84.6%) who had consultations with the participating oncologists at baseline and/or follow-up were assessed regarding their distress using the Hospital Anxiety and Depression Scale, satisfaction with the consultation, and trust in their oncologist after the consultation.At the follow-up survey, the performance scores of the IG had improved significantly, in terms of their emotional support (P = .011), setting up a supportive environment (P = .002), and ability to deliver information (P = .001), compared with those of the CG. Oncologists in the IG were rated higher at follow-up than those in the CG in terms of their confidence in themselves (P = .001). Patients who met with oncologists after they had undergone the CST were significantly less depressed than those who met with oncologists in the CG (P = .027). However, the CST program did not affect patient satisfaction with oncologists' style of communication.A CST program based on patient preferences is effective for both oncologists and patients with cancer. Oncologists should consider CST as an approach to enhancing their communication skills.
Oncogenic BRAF(V600E) Promotes Stromal Cell-Mediated Immunosuppression Via Induction of Interleukin-1 in Melanoma
Authors: Jahan S. Khalili, Shujuan Liu, Tania G. Rodríguez-Cruz, Mayra Whittington, Seth Wardell, Chengwen Liu, Minying Zhang, Zachary A. Cooper, Dennie T. Frederick, Yufeng Li, Min Zhang, Richard W. Joseph, Chantale Bernatchez, Suhendan Ekmekcioglu, Elizabeth Grimm, Laszlo G. Radvanyi, Richard E. Davis, Michael A. Davies, Jennifer A. Wargo, Patrick Hwu, Gregory Lizée
Journal: Clinical Cancer Research (2012)

Abstract Purpose: In this study, we assessed the specific role of BRAF(V600E) signaling in modulating the expression of immune regulatory genes in melanoma, in addition to analyzing downstream induction of immune suppression by primary human melanoma tumor-associated fibroblasts (TAF). Experimental Design: Primary human melanocytes and melanoma cell lines were transduced to express WT or V600E forms of BRAF, followed by gene expression analysis. The BRAF(V600E) inhibitor vemurafenib was used to confirm targets in BRAF(V600E)-positive melanoma cell lines and in tumors from melanoma patients undergoing inhibitor treatment. TAF lines generated from melanoma patient biopsies were tested for their ability to inhibit the function of tumor antigen-specific T cells, before and following treatment with BRAF(V600E)-upregulated immune modulators. Transcriptional analysis of treated TAFs was conducted to identify potential mediators of T-cell suppression. Results: Expression of BRAF(V600E) induced transcription of interleukin 1 alpha (IL-1α) and IL-1β in melanocytes and melanoma cell lines. Further, vemurafenib reduced the expression of IL-1 protein in melanoma cell lines and most notably in human tumor biopsies from 11 of 12 melanoma patients undergoing inhibitor treatment. Treatment of melanoma-patient–derived TAFs with IL-1α/β significantly enhanced their ability to suppress the proliferation and function of melanoma-specific cytotoxic T cells, and this inhibition was partially attributable to upregulation by IL-1 of COX-2 and the PD-1 ligands PD-L1 and PD-L2 in TAFs. Conclusions: This study reveals a novel mechanism of immune suppression sensitive to BRAF(V600E) inhibition, and indicates that clinical blockade of IL-1 may benefit patients with BRAF wild-type tumors and potentially synergize with immunotherapeutic interventions. Clin Cancer Res; 18(19); 5329–40. ©2012 AACR.
Multiple sclerosis in the course of systemic sclerosis
Authors: E Chroni
Journal: Annals of the Rheumatic Diseases (2002)

In an article on Rubens' painting "The Three Graces" Dequeker suggests that hypermobility is a medical explanation of the seeming scoliosis and Trendelenburg sign in the middle figure . 1 But the posture of this middle figure should probably be interpreted as an artistic phenomenon without medical reference.Sculptors in classical Greek and Roman periods often used the contrapposto posture.In this, by putting most weight on one leg, the other leg can be shown in a relaxed and semiflexed position.This undulating between tension and relaxation will animate the figure.A person with normal muscular function and a normal back can perfectly well pose in this way with relaxed hip abductors on the weightbearing side, a descending hip on the opposite side, and a compensating scoliotic posture.This posture is facilitated by support from the arm as in Rubens' painting.If the person tries to take a forward step, relaxation of the muscles of the weightbearing hip can no longer be maintained, and the positive Trendelenburg sign will disappear.In the Renaissance period the use of this contrapposto posture was revived.During his stay in Rome Rubens eagerly studied the then recently excavated Laokoön sculpture with its three distorted figures. 2 He often used such distorted postures in his paintings to give the impression of vigorous muscular characters capable of performing great tasks.The best example is probably "The Debarkation at Marseilles" in the Maria de Medici cycle from 1622 to 1625 for the Luxembourg Palace in Paris. 3 Here, three young women, nereides, with curved muscular backs at the bottom of the picture nearly seem to carry the ship of Maria de Medici.
SIGN-R1 Contributes to Protection against Lethal Pneumococcal Infection in Mice
Authors: Astrid Lanoue, Menna R. Clatworthy, Philippa Smith, Sheila Green, Michael J. Townsend, Helen E. Jolin, Kenneth G.C. Smith, Padraic G. Fallon, Andrew N.J. McKenzie
Journal: The Journal of Experimental Medicine (2004)

Rapid clearance of pathogens is essential for successful control of pyogenic bacterial infection. Previous experiments have shown that antibody to specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1 inhibits uptake of capsular polysaccharide by marginal zone macrophages, suggesting a role for SIGN-R1 in this process. We now demonstrate that mice lacking SIGN-R1 (a mouse homologue of human dendritic cell–SIGN receptor) are significantly more susceptible to Streptococcus pneumoniae infection and fail to clear S. pneumoniae from the circulation. Marginal zone and peritoneal macrophages show impaired bacterial recognition associated with an inability to bind T-independent type 2 antigens such as dextran. Our work represents the first evidence for a protective in vivo role for a SIGN family molecule.
Cellular origin and pathophysiology of chronic lymphocytic leukemia
Authors: Marc Seifert, Ludger Sellmann, Johannes Bloehdorn, Frederik Wein, Stephan Stilgenbauer, Jan Dürig, Ralf Küppers
Journal: The Journal of Experimental Medicine (2012)

The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information is critical to understanding its pathogenesis. Transcriptome analyses of CLL and the main normal B cell subsets from human blood and spleen revealed that immunoglobulin variable region (IgV) gene unmutated CLL derives from unmutated mature CD5+ B cells and mutated CLL derives from a distinct, previously unrecognized CD5+CD27+ post–germinal center B cell subset. Stereotyped V gene rearrangements are enriched among CD5+ B cells, providing independent evidence for a CD5+ B cell derivation of CLL. Notably, these CD5+ B cell populations include oligoclonal expansions already found in young healthy adults, putatively representing an early phase in CLL development before the CLL precursor lesion monoclonal B cell lymphocytosis. Finally, we identified deregulated proteins, including EBF1 and KLF transcription factors, that were not detected in previous comparisons of CLL and conventional B cells.
Multiple sessile polypoid lesions in the stomach
Authors: C Tiong, C-J Tai, W-Y Chen, C-C Chang, F-M Suk
Journal: Gut (2007)

A 75-year-old man with myelofibrosis was diagnosed in October 2002. Blast crisis was noted several times in between October 2002 and September 2005 so hydroxyurea and interferon were given. In addition, he also received radiotherapy …
H4(D10S170), a gene frequently rearranged in papillary thyroid carcinoma, is fused to the platelet-derived growth factor receptor β gene in atypical chronic myeloid leukemia with t(5;10)(q33;q22)
Authors: Juerg Schwaller, Ema Anastasiadou, Danielle Cain, Jeff Kutok, Sarah Wojiski, Ifor R. Williams, Roberta LaStarza, Barbara Crescenzi, David W. Sternberg, Patrick Andreasson, Roberta Schiavo, Salvatore Siena, Cristina Mecucci, D. Gary Gilliland
Journal: Blood (2001)
Multicenter Phase II Study of Oral Bexarotene for Patients With Metastatic Breast Cancer
Authors: Francisco J. Esteva, John Glaspy, Said Baidas, Leslie Laufman, Laura Hutchins, Maura Dickler, Debu Tripathy, Roger Cohen, Angela DeMichele, Richard C. Yocum, C. Kent Osborne, Daniel F. Hayes, Gabriel N. Hortobagyi, Eric Winer, George D. Demetri
Journal: Journal of Clinical Oncology (2003)

Bexarotene is a retinoid X receptor-selective retinoid that has preclinical antitumor activity in breast cancer. We evaluated the efficacy and safety of oral bexarotene in the treatment of patients with metastatic breast cancer.The following three groups of patients were treated: hormone-refractory, chemotherapy-refractory, and tamoxifen-resistant patients. Patients in the first two groups were treated with bexarotene alone, whereas the tamoxifen-resistant patients received both tamoxifen and bexarotene. Patients in all groups were randomly assigned to receive bexarotene at either 200 or 500 mg/m(2)/d.One hundred forty-eight patients were randomized; 145 patients were treated. Of 48 hormone-refractory patients, there were two partial responses (6%) and 10 patients with stable disease lasting more than 6 months; of 47 chemotherapy-refractory patients, there were two partial responses (6%) and five patients with stable disease; and of 51 tamoxifen-resistant patients, there was one partial response (3%) and 11 patients with stable disease. All partial responses occurred at the 200-mg/m(2)/d dose. The projected median time to progression across all of the arms was 8 to 10 weeks. There were no drug-related deaths, and only two patients had drug-related serious adverse events. The most common drug-related adverse events were hypertriglyceridemia (84%), dry skin (34%), asthenia (30%), and headache (27%). There were no cases of pancreatitis.The efficacy of bexarotene in patients with refractory metastatic breast cancer is limited. However, it is an oral agent with minimal toxicity and a unique mechanism of action, which produced clinical benefit in approximately 20% of patients. Future efforts should define populations likely to benefit from this agent.