tbuckley/cabot-search huggingface dataset:
Targeting Platelet-Derived Growth Factor Receptor on Endothelial Cells of Multidrug-Resistant Prostate Cancer
Authors: Sun-Jin Kim, Hisanori Uehara, Sertac Yazici, Joseph Erik Busby, Toru Nakamura, Junqin He, Marva Maya, Christopher Logothetis, Paul Mathew, Xuemei Wang, Kim-Anh Do, Dominic Fan, Isaiah J. Fidler
Journal: JNCI Journal of the National Cancer Institute (2006)

Inhibiting phosphorylation of platelet-derived growth factor receptor (PDGFR) by treatment with the PDGFR kinase inhibitor imatinib and the chemotherapeutic agent paclitaxel reduces the incidence and size of human prostate cancer bone lesions in nude mice. Because tumor cells and tumor-associated endothelial cells express activated PDGFR, the primary target for imatinib has been unclear.We selected multidrug-resistant human PC-3MM2 prostate cancer cells (termed PC-3MM2-MDR cells) by culturing them in increasing concentrations of paclitaxel. PC-3MM2-MDR cells were implanted into one tibia of 80 nude mice. Two weeks later, the mice were randomly assigned to receive distilled water (control group), paclitaxel, imatinib, or imatinib plus paclitaxel for 10 weeks (20 mice per group). Tumor incidence and weight, bone structure preservation and osteolysis, and the incidence of lymph node metastasis were determined. The phosphorylation status of PDGFR on tumor cells and tumor-associated endothelial cells and levels of apoptosis were examined with immunohistochemical analyses. Microvessel density was assessed as the number of cells expressing CD31/platelet endothelial cell adhesion molecule 1 (PECAM-1). All statistical tests were two-sided.PC-3MM2-MDR cells were resistant to paclitaxel and imatinib in vitro. Treatment of implanted mice with imatinib plus paclitaxel led to statistically significant decreases in bone tumor incidence (control = 19 mice with tumors of 19 mice total; imatinib plus paclitaxel = four of 18 mice; P < .001), median tumor weight (control = 1.3 g, interquartile range [IQR] = 1.0-1.9; imatinib plus paclitaxel = 0.1 g, IQR = 0-0.3; P < .001), bone lysis, and the incidence of lymph node metastasis (control = 19 of 19 mice total; imatinib plus paclitaxel = three of 18 mice; P < .001). Treatment with imatinib alone had similar effects, and imatinib treatment also inhibited phosphorylation of PDGFR on tumor cells and tumor-associated endothelial cells and increased the level of apoptosis of endothelial cells, but not tumor cells. Treatment with imatinib and more so with imatinib and paclitaxel decreased mean vessel density (three CD31/PECAM-1-positive cells, 95% confidence interval [CI] = 0 to 9; and control group = 38 CD31/PECAM-1-positive cells, 95% CI = 17 to 59) (P < .001), which was followed by apoptosis of tumor cells.Tumor-associated endothelial cells, rather than tumor cells themselves, appear to be the target for imatinib in prostate cancer bone metastasis.
Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.
Authors: T De Smedt, B Pajak, E Muraille, L Lespagnard, E Heinen, P De Baetselier, J Urbain, O Leo, M Moser
Journal: The Journal of Experimental Medicine (1996)

Dendritic cells (DC) are described as "nature's adjuvant," since they have the capacity to sensitize T cells in vivo upon first encounter with the antigen. The potent accessory properties of DC appear to develop sequentially. In particular, the ability to process antigens and to sensitize native T cells develops in sequence, a process termed "maturation" that is well described in vitro. Here, we obtain evidence for maturation in vivo in response to the bacterial product lipopolysaccharide (LPS). Before LPS treatment, many DC are found at the margin between the red and white pulp. These cells lack the M342 and DEC-205 markers, but process soluble proteins effectively. 6 h after LPS, DC with the M342 and DEC-205 markers are found in increased numbers in the T cell areas. These cells have a reduced capacity to process proteins, but show increases in the B7 costimulator and T cell stimulatory capacity. 48 h after LPS, the number of DC in the spleen is reduced markedly. We interpret these findings to mean that LPS can cause DC in the marginal zone to mature and to migrate into and then out of the T cell areas.
The additive effect of sclerotherapy to patients receiving repeated endoscopic variceal ligation: A prospective, randomized trial
Authors: Gin-ho Lo, Kwok-hung Lai, Jin-shiung Cheng, Chiun-ku Lin, Jia-sheng Huang, Ping-i Hsu, Hui-chun Huang, Hung-ting Chiang
Journal: Hepatology (1998)

Endoscopic variceal ligation (EVL) is a new technique designed to manage esophageal varices. The effect of sclerotherapy following repeated banding ligation remains unknown. Seventy-two patients with a history of esophageal variceal bleeding received regular EVL until variceal disappearance or until left with residual small varices. Subsequently, patients were randomized to receive sclerotherapy (Group 1, 37 patients) or serve as a control (Group 2, 35 patients). Group 1 received one to two sessions of low-dose sclerotherapy to achieve complete variceal disappearance. After a mean follow-up of 2 years, 4 months, recurrent esophageal varices developed in 14% of Group 1 and 43% of Group 2 (P < .02). Rebleeding was encountered in 8% of Group 1 versus 31% of Group 2 (P = .01). One case of esophageal stricture (2.7%) was encountered in Group 1. One patient in Group 1, compared with 3 patients in Group 2, died of massive variceal bleeding (P > .05). The multivariate Cox model indicated that treatment was the only factor predictive of variceal recurrence, and both Child-Pugh class and treatment were factors predictive of variceal rebleeding. The addition of low-dose sclerotherapy following repeated banding ligations proved safe and effective in the prevention of recurrence of esophageal varices and rebleeding.
Antitumor effects of HSV-TK–engineered donor lymphocytes after allogeneic stem-cell transplantation
Authors: Fabio Ciceri, Chiara Bonini, Sarah Marktel, Elisabetta Zappone, Paolo Servida, Massimo Bernardi, Alessandra Pescarollo, Attilio Bondanza, Jacopo Peccatori, Silvano Rossini, Zulma Magnani, Monica Salomoni, Claudia Benati, Maurilio Ponzoni, Luciano Callegaro, Paolo Corradini, Marco Bregni, Catia Traversari, Claudio Bordignon
Journal: Blood (2007)
Pharmacological Control of the Cerebral Circulation
Authors: O U Scremin
Journal: The Annual Review of Pharmacology and Toxicology (1991)

This review is about control of a physiological variable; what that variable's function is and how it is regulated must be discussed first to establish a rational basis for its controL The reader is referred to some excellent recent reviews on regulation of cerebral blood flow (CBF)1 (1-3). We emphasize here some functions of CBF that are not so obvious and have been largely overlooked. Cerebral blood vessels evolved as the volume of neural structures made diffusion an inefficient process to supply oxygen and nutrients to nerve cells. This being the primary drive, a close correlation can be found between intercapillary distance or capillary surface area and the level of energy exchange of the various brain regions (4-6). This structurally determined
TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis
Authors: Mario Noti, Nadia Corazza, Christoph Mueller, Barbara Berger, Thomas Brunner
Journal: The Journal of Experimental Medicine (2010)

Although tumor necrosis factor (α) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate–induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis.
Cancer at Insulin Injection Site
Authors: Elliott Eisenbud
Journal: JAMA (1975)

THERE is a large and generally anecdotal literature suggesting a relationship between trauma and subsequent development of cancer. We report the development of cancer at the site of a common type of trauma, that of long-term insulin injection. <h3>Report of a Case</h3> A 35-year-old woman, in whom insulinrequiring diabetes mellitus had developed at age 15, had been receiving one daily dose of 15 units of insulin zinc suspension (Lente) for the past ten years. Her diabetes was complicated by retinopathy, neurogenic bladder, diarrhea, orthostatic hypotension, peripheral neuropathy, and proteinuria. Six months before admission she noted a 2 × 2-cm nontender swelling on the side of the right thigh, which she attributed to a local allergic reaction to insulin. One month before admission the swelling increased rapidly, and she developed pain in the right thigh, groin, and lower part of the back. Physical examination revealed a 10 × 12cm firm, nontender
The influence of hyperinflation on body composition and cytokine profile in patients with COPD
Authors: Renata Rubinsztajn, Tadeusz Przybylowski, Marta Maskey-Warzechowska, Magdalena Paplinska-Goryca, Patrycja Nejman-Gryz, Krzysztof Karwat, Ryszarda Chazan
Journal: European Respiratory Journal (2013)

Body composition is an important prognostic factor in patients with COPD. The decrease in fat free mass (FFM), muscle mass (MM) and increase in visceral fat is associated with an elevated secretion of cytokines which promote systemic inflammation.  Aim: to evaluate body composition and the cytokine profile in patients with COPD in relation with the presence of hyperinflation.  The study group consisted of 149 patients with stable COPD aged 68±8.8 yrs with a mean FEV 1  55.9±18.9 % predicted. The patients underwent spirometry and bodypletysmography. Hyperinflation was defined as RV%TLC > 48% and > 126% predicted. Body composition was analyzed by bioimpedance. The following serum inflammatory markers were evaluated: C-reactive protein, IL-6, IL-8, TNF alpha, CC16, adiponectin and resistin.  Hyperinflation was found in 96 patients (group A), more frequently in women (49/61 vs. 47/88, p  We found significantly higher serum concentrations of IL-6, resistin and CRP in group A.  Conclusions:  1/ Although BMI is not different in COPD patients with and without hyperinflation, patients with hyperinflation have a lower FFM, TBW MM and a higher proportion of fat tissue.  2/ Hyperinflation is associated with systemic inflammation and could therefore be a negative prognostic factor in COPD patients.
The impact of DM on MHC class II–restricted antigen presentation can be altered by manipulation of MHC–peptide kinetic stability
Authors: Christopher A. Lazarski, Francisco A. Chaves, Andrea J. Sant
Journal: The Journal of Experimental Medicine (2006)

DM edits the peptide repertoire presented by major histocompatibility complex class II molecules by professional antigen-presenting cells (APCs), favoring presentation of some peptides over others. Despite considerable research by many laboratories, there is still significant uncertainty regarding the biochemical attributes of class II–peptide complexes that govern their susceptibility to DM editing. Here, using APCs that either do or do not express DM and a set of unrelated antigens, we found that the intrinsic kinetic stability of class II–peptide complexes is tightly correlated with the effects of DM editing within APCs. Furthermore, through the use of kinetic stability variants of three independent peptides, we demonstrate that increasing or decreasing the kinetic stability of class II–peptide complexes causes a corresponding alteration in DM editing. Finally, we show that the spontaneous kinetic stability of class II complexes correlates directly with the efficiency of presentation by DM+ APCs and the immunodominance of that class II–peptide complex during an immune response. Collectively, these results suggest that the pattern of DM editing in APCs can be intentionally changed by modifying class II–peptide interactions, leading to the desired hierarchy of presentation on APCs, thereby promoting recruitment of CD4 T cells specific for the preferred peptides during an immune response.
Influence of Coronary Artery Bypass and Age on Clinical Performance After Aortic and Mitral Valve Replacement With Biological and Mechanical Prostheses
Authors: W.R. Eric Jamieson, A. Ian Munro, Lawrence H. Burr, Eva Germann, Robert T. Miyagishima, Hilton Ling
Journal: Circulation (1995)

Abstract The influence of prosthetic type, age, and coronary artery bypass grafting (CABG) on valve-related complications by valve position was evaluated in a population of 2353 bioprosthesis patients (mean age, 66.5 years; range, 13 to 89 years) and in a population of 1112 mechanical prosthesis patients (mean age, 59.1 years; range, 13 to 91 years). The follow-up was complete to 96% and 98%, respectively, for the bioprosthesis and mechanical prosthesis groups. The patient groups were evaluated by actuarial assessment of survival and valve complications and composites. Preoperative factors were evaluated for determination of significant independent predictors by multivariate proportional-hazard regression analysis. CABG was an influential factor in the actuarial analysis. Survival was superior for aortic mechanical replacements without CABG and for mitral replacements, both biological and mechanical, without CABG ( P &lt;.05). The freedom from thromboembolism (TE) and antithromboembolic hemorrhage (ATH) was greater for biological prostheses with and without CABG for aortic replacements ( P &lt;.05) but not for mitral replacements ( P =NS). The freedom from valve-related mortality was not influenced by CABG for either position ( P =NS). The freedom from valve-related reoperation was greater for biological prostheses with CABG than without CABG for both aortic and mitral replacements ( P &lt;.05). The evaluation of covariates as independent predictors revealed CABG to be a nonpredictor for aortic valve replacement (AVR) ( P =NS) but a predictor of survival and valve-related reoperation for mitral valve replacement (MVR) ( P &lt;.05). With AVR, biological prostheses predicted greater freedom from valve-related mortality and TE and ATH ( P &lt;.05) and for MVR for TE and ATH ( P &lt;.05). Valve position was not a predictor otherwise ( P =NS). Advancing age was a significant covariate for AVR for all areas of assessment. Advancing age for MVR provided a lower rate of survival and greater freedom from valve-related mortality and reoperation ( P &lt;.05). The clinical performance of valvular prostheses is influenced to a greater degree by valve type and age than by CABG.
Domains of deception
Authors: David M. Buss
Journal: Behavioral and Brain Sciences (2011)

Abstract The von Hippel &amp; Trivers theory of self-deception will gain added traction by identifying psychological design features that come into play in different domains of deception. These include the domains of mating, kinship, coalition formation, status hierarchy negotiation, parenting, friendship, and enmity. Exploring these domains will uncover psychological adaptations and sex-differentiated patterns of self-deception that are logically entailed by their theory.
CTLA4 Blockade Broadens the Peripheral T-Cell Receptor Repertoire
Authors: Lidia Robert, Jennifer Tsoi, Xiaoyan Wang, Ryan Emerson, Blanca Homet, Thinle Chodon, Stephen Mok, Rong Rong Huang, Alistair J. Cochran, Begoña Comin-Anduix, Richard C. Koya, Thomas G. Graeber, Harlan Robins, Antoni Ribas
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To evaluate the immunomodulatory effects of cytotoxic T–lymphocyte-associated protein 4 (CTLA4) blockade with tremelimumab in peripheral blood mononuclear cells (PBMC). Experimental Design: We used next-generation sequencing to study the complementarity-determining region 3 (CDR3) from the rearranged T-cell receptor (TCR) variable beta (V-beta) in PBMCs of 21 patients, at baseline and 30 to 60 days after receiving tremelimumab. Results: After receiving tremelimumab, there was a median of 30% increase in unique productive sequences of TCR V-beta CDR3 in 19 out of 21 patients, and a median decrease of 30% in only 2 out of 21 patients. These changes were significant for richness (P = 0.01) and for Shannon index diversity (P = 0.04). In comparison, serially collected PBMCs from four healthy donors did not show a significant change in TCR V-beta CDR3 diversity over 1 year. There was a significant difference in the total unique productive TCR V-beta CDR3 sequences between patients experiencing toxicity with tremelimumab compared with patients without toxicity (P = 0.05). No relevant differences were noted between clinical responders and nonresponders. Conclusions: CTLA4 blockade with tremelimumab diversifies the peripheral T-cell pool, representing a pharmacodynamic effect of how this class of antibodies modulates the human immune system. Clin Cancer Res; 20(9); 2424–32. ©2014 AACR.
Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways
Authors: Matias Simons, Joachim Gloy, Athina Ganner, Axel Bullerkotte, Mikhail Bashkurov, Corinna Krönig, Bernhard Schermer, Thomas Benzing, Olga A Cabello, Andreas Jenny, Marek Mlodzik, Bozena Polok, Wolfgang Driever, Tomoko Obara, Gerd Walz
Journal: Nature Genetics (2005)
Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease
Authors: Holm H Uhlig
Journal: Gut (2013)

Inflammatory bowel disease (IBD), encompassing Crohn9s disease and ulcerative colitis, has multifactorial aetiology with complex interactions between genetic and environmental factors. Over 150 genetic loci are associated with IBD. The genetic contribution of the majority of those loci towards explained heritability is low. Recent studies have reported an increasing spectrum of human monogenic diseases that can present with IBD-like intestinal inflammation. A substantial proportion of patients with those genetic defects present with very early onset of intestinal inflammation. The 40 monogenic defects with IBD-like pathology selected in this review can be grouped into defects in intestinal epithelial barrier and stress response, immunodeficiencies affecting granulocyte and phagocyte activity, hyper- and autoinflammatory disorders as well as defects with disturbed T and B lymphocyte selection and activation. In addition, there are defects in immune regulation affecting regulatory T cell activity and interleukin (IL)-10 signalling. Related to the variable penetrance of the IBD-like phenotype, there is a likely role for modifier genes and gene–environment interactions. Treatment options in this heterogeneous group of disorders range from anti-inflammatory and immunosuppressive therapy to blockade of tumour necrosis factor α and IL-1β, surgery, haematopoietic stem cell transplantation or gene therapy. Understanding of prototypic monogenic 'orphan' diseases cannot only provide treatment options for the affected patients but also inform on immunological mechanisms and complement the functional understanding of the pathogenesis of IBD.
Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study
Authors: S Elsenbruch, C Rosenberger, P Enck, M Forsting, M Schedlowski, E R Gizewski
Journal: Gut (2009)

<h3>Objective</h3> To address the role of anxiety and depression symptoms in altered pain processing in irritable bowel syndrome (IBS). <h3>Design</h3> In this functional magnetic resonance imaging study, the blood oxygen level-dependent (BOLD) response to rectal distensions delivered at previously determined individual discomfort thresholds was assessed. <h3>Patients</h3> 15 female patients with irritable bowel syndrome (IBS) and with normal rectal pain thresholds, and 12 healthy women. <h3>Measures</h3> The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences in pain-induced brain activation with and without controlling for HADS scores were evaluated. <h3>Results</h3> Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively, as confounding variables led to a loss of significant group differences. <h3>Conclusions</h3> Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affective–motivational aspects of the pain response.
Hepatitis C in adults and adolescents with hemophilia: A randomized, controlled trial of interferon alfa-2b and ribavirin
Authors: Michael W. Fried, Joy Peter, Keith Hoots, Paul J. Gaglio, Donald Talbut, Charleton P. Davis, Nigel S. Key, Gilbert C. White, Lauren Lindblad, Frederick R. Rickles, Thomas C. Abshire
Journal: Hepatology (2002)

Adolescents and adults with inherited disorders of coagulation have one of the highest prevalence rates of hepatitis C among known risk groups. Few data are available on the use of combination therapy with interferon and ribavirin in this population. Patients 13 years of age and older who were positive for hepatitis C virus (HCV) RNA by polymerase chain reaction and negative for human immunodeficiency virus were randomized to receive interferon alfa-2b (3 million units 3 times a week) plus ribavirin (1,000 mg/day) or interferon alfa-2b alone for 48 weeks with 24 weeks of posttreatment follow-up. Patients started on interferon alone who remained positive for HCV RNA at week 12 crossed over to treatment with interferon plus ribavirin. A total of 113 patients were treated. Thirty-seven patients were younger than 18 years. At the end of treatment, 18 of 56 (32%) treated with interferon plus ribavirin and 6 of 57 (11%) treated with interferon alone were negative for HCV RNA ( P = .005). Sustained virologic response in the combination arm was 29% (16 of 56) compared with 7% (4 of 57) for those started on interferon alone ( P = .027). Among adolescents younger than 18 years who were treated with combination therapy, 10 of 17 (59%) had sustained response compared with 6 of 39 (15%) of adult patients on the same regimen ( P = .001). In conclusion, in this U.S. multicenter, randomized trial of therapy for HCV in patients with inherited bleeding disorders, sustained virologic response rate was significantly improved for patients treated with interferon and ribavirin compared with those started on interferon alone. Adolescents treated with combination therapy had a significantly higher sustained response than adults did on the same regimen.