tbuckley/cabot-search huggingface dataset:
The Interplay and Etiological Continuity of Neuroticism, Difficulties, and Life Events in the Etiology of Major and Subsyndromal, First and Recurrent Depressive Episodes in Later Life
Authors: Johan Ormel, Albertine J. Oldehinkel, Els I. Brilman
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Stressful life events, long-term difficulties, and high neuroticism are established risk factors for depression. Less is known about their role in late-life depression, how they modify or mediate one another’s effects, and whether this differs between major and subsyndromal, first and recurrent episodes. METHOD: The authors used a prospective case-control design nested in a community survey of elderly subjects that included a measure of neuroticism. They compared 83 survey participants who subsequently developed a depressive episode with 83 randomly selected comparison participants. The authors determined dates of onset, history, and severity of episodes and dates of occurrence and severity of stressful life events and difficulties. RESULTS: Stressful life events did not mediate the effects of high neuroticism and difficulties at onset, possibly because of the uncontrollable nature of common stressful life events in later life. Without both high neuroticism and difficulties, stressful life events did not increase risk. High neuroticism and difficulties increased risk, even without a stressful life event. In the presence of high neuroticism and/or difficulties, the depressogenic effect of stressful life events was substantial, suggesting effect modification. The authors found no evidence to suggest etiological discontinuity between major and subsyndromal episodes. First and recurrent episodes showed a discontinuous pattern of associations. Severe stressful life events had weaker associations, but high neuroticism and mild stressful life events had stronger associations with recurrent than with first episodes. CONCLUSIONS: This study demonstrated the usefulness of a dynamic stress-vulnerability model for understanding late-life depression. Evidence was found suggesting etiological discontinuity between first and recurrent but not between major and subsyndromal episodes.
The effect of thermal processing on the IgE reactivity of the non‐specific lipid transfer protein from apple, Mal d 3
Authors: A. I. Sancho, N. M. Rigby, L. Zuidmeer, R. Asero, G. Mistrello, S. Amato, E. González‐Mancebo, M. Fernández‐Rivas, R. van Ree, E. N. C. Mills
Journal: Allergy (2005)

Background: Non‐specific lipid transfer proteins (LTPs) are involved in allergy to fresh and processed fruits. We have investigated the effect of thermal treatment and glycation on the physico‐chemical and IgE‐binding properties of the LTP from apple (Mal d 3). Methods: Mal d 3 was purified from apple peel and the effect of heating in the absence and presence of glucose investigated by CD spectroscopy, electrospray and MALDI‐TOF mass spectrometry. IgE reactivity was determined by RAST and immunoblot inhibition, SPT and basophil histamine release test. Results: The identity and IgE reactivity of purified Mal d 3 was confirmed. Mild heat treatment (90°C, 20 min) in the absence or presence of glucose did not alter its IgE reactivity. More severe heat treatment (100°C, 2 h) induced minor changes in protein structure, but a significant decrease in IgE‐binding (30‐fold) and biological activity (100‐ to 1000‐fold). Addition of glucose resulted in up to four glucose residues attached to Mal d 3 and only a 2‐ and 10‐fold decrease of IgE‐binding and biological activity, respectively. Conclusions: Only severe heat treatment caused a significant decrease in the allergenicity of Mal d 3 but glycation had a protective effect. The presence of sugars in fruits may contribute to the thermostability of the allergenic activity of LTP in heat‐processed foods.
Therapeutic Relevance of Osteoprotegerin Gene Therapy in Osteosarcoma: Blockade of the Vicious Cycle between Tumor Cell Proliferation and Bone Resorption
Authors: François Lamoureux, Peggy Richard, Yohann Wittrant, Séverine Battaglia, Paul Pilet, Valérie Trichet, Frédéric Blanchard, François Gouin, Bruno Pitard, Dominique Heymann, Françoise Redini
Journal: Cancer Research (2007)

Abstract Osteosarcoma is the most frequent primary bone tumor that develops mainly in the young, the median age of diagnosis being 18 years. Despite improvement in osteosarcoma treatment, survival rate is only 30% at 5 years for patients with pulmonary metastases at diagnosis. This warrants exploration of new therapeutic options, and among them, osteoprotegerin (OPG), a naturally occurring protein that inhibits bone resorption, is very promising in blocking the vicious cycle between bone resorption and tumor proliferation that takes place during tumor development in bone site. As OPG binds and inhibits the activity of tumor necrosis factor–related apoptosis-inducing ligand, the truncated form of murine OPG 1-194 was used. The cDNA encoding OPG was administered by gene transfer using replication-defective adenoviral vector or was associated with an amphiphilic polymer in two models of rodent osteosarcoma. In both models, OPG gene transfer was effective in preventing the formation of osteolytic lesions associated with osteosarcoma development, in reducing the tumor incidence and the local tumor growth, leading to a 4-fold augmentation of mice survival 28 days postimplantation. On the contrary, OPG did not prevent the development of pulmonary metastasis alone, suggesting that bone environment is necessary for OPG therapeutic efficacy. Because OPG has no direct activity on osteosarcoma cells in vitro (cell binding, cell proliferation, apoptosis, or cell cycle distribution), we show that OPG exerts indirect inhibitory effect on tumor progression through the inhibition of RANKL whose production is enhanced in bone tumor environment, leading to osteolysis inhibition as reflected by osteoclast number decrease. [Cancer Res 2007;67(15):7308–18]
PWE-200 Mr Enterography is a Useful test in the Investigation of Small Bowel Disease
Authors: S Soteriadou, K White, R Filobbos, J K Limdi
Journal: Gut (2013)

<h3>Introduction</h3> MR enterography (MRE) aids assessment of small bowel (SB) inflammatory bowel disease (IBD). We aimed to determine the frequency and clinical impact of incidental findings detected by MRE in patients with suspected or known Crohn’s disease (CD). <h3>Methods</h3> We conducted a retrospective review of 948 MRE studies performed between June 2009 and December 2012 at our institution. Clinical data (demographics, disease characteristics and therapy) were obtained from electronic patient records. Incidental findings were defined as unexpected lesions in or outside the small intestine, previously unknown or unsuspected at the time of referral and unrelated to IBD. <h3>Results</h3> Of 948 MRE studies 445 patients had a diagnosis of IBD, 385 had CD, 54 had ulcerative colitis and 16 had IBD unclassified (IBDU). Of 385 CD patients, 224 were female, mean age 36 (range 12–72) and median follow up of 4 years (range 0–39). Abnormalities were noted in 285 scans, 162 active non-stricturing, 109 active stricturing and 13-fibrostenosis. Within active groups were 29 fistulae and 12 abscesses in 33 patients. Incidental findings included colitis (10), gallstones (17), ovarian cyst (15), sacroileitis (1), renal cyst (10), hepatic cyst (10), splenic haemangioma (1), mesenteric abscess (1), adrenal nodule (2), uterine fibroid (4), chronic pancreatitis (1) and splenomegaly (2) associated with portal vein thrombosis in and varices. 70 studies were performed in UC or IBDU; mean age 34 (range 15–82) 39 were female. Small bowel thickening with signs of active inflammation were seen in 9/13. Other findings included a fluid filled collection in the right ischio-anal fossa, pancreatic divisum, gallstones and liver, ovarian and Nabothian cysts, colitis in 6 and colonic polyps in 1. Indications for MRE in the non-IBD group (503 patients) included iron deficiency anaemia, abdominal pain, weight loss, diarrhoea, vomiting, abnormal colonoscopy or intra-abdominal abscess. Findings included small bowel thickening (4), sub-acute small bowel obstruction (2), small bowel malignancies (2), small bowel stricture (1) and small bowel intussusception (1). Incidental findings included ovarian, hepatic and renal cysts, adrenal adenoma, ascites, splenic and liver haemangioma, AAA, PUJ obstruction, liver metastases, gallstones, gallbladder polyp, pelvic abscess, uterine fibroids, large bowel stricture, diverticular disease, cirrhosis, lymphadenopathy, horseshoe kidney, atrophic pancreas and acute appendicitis. <h3>Conclusion</h3> A small but significant proportion of patients have important incidental findings at MRE. MRE can add meaningfully to the investigation of SB pathology. A careful selection of patients can be achieved through a collaborative approach between radiologists and clinicians. <h3>Disclosure of Interest</h3> None Declared.
Gorilla class I major histocompatibility complex alleles: comparison to human and chimpanzee class I.
Authors: D A Lawlor, E Warren, P Taylor, P Parham
Journal: The Journal of Experimental Medicine (1991)

14 gorilla class I major histocompatibility complex (MHC) alleles have been isolated, sequenced, and compared to their counterparts in humans and chimpanzees. Gorilla homologues of HLA-A, -B, and -C were readily identified, and four Gogo-A, four Gogo-B, and five Gogo-C alleles were defined. In addition, an unusual Gogo class I gene with features in common with HLA-A and its related pseudogene, HLA-H, is described. None of the gorilla alleles is identical or even closely related to known class I alleles and each encodes a unique antigen recognition site. However, the majority of polymorphic substitutions and sequence motifs of gorilla class I alleles are shared with the human or chimpanzee systems. In particular, elements shared with HLA-A2 and HLA-B27 are found in Gogo-A and -B alleles. Diversity at the Gogo-B locus is less than at the Gogo-A locus, a trend the opposite of that seen for HLA-A and -B. The Gogo-C locus also appears to have limited polymorphism compared to Gogo-A. Two basic Gogo-C motifs were found and they segregate with distinctive sets of HLA-C alleles. HLA-A allels are divided into five families derived from two ancient lineages. All chimpanzee A alleles derived from one of these lineages and all gorilla alleles derive from the other. Unlike chimpanzee Patr-A alleles, the Gogo-A alleles do not clearly partition with one of the HLA-A families but have similarities with two. Overall, gorilla class I diversity appears from this sampling to show more distinctions from class I HLA than found for chimpanzee class I.
Preclinical Testing of Tissue-Engineered Heart Valves Re-Endothelialized Under Simulated Physiological Conditions
Authors: Artur Lichtenberg, Igor Tudorache, Serghei Cebotari, Mark Suprunov, Greta Tudorache, Heidi Goerler, Joon-Keun Park, Denise Hilfiker-Kleiner, Stefanie Ringes-Lichtenberg, Matthias Karck, Gudrun Brandes, Andres Hilfiker, Axel Haverich
Journal: Circulation (2006)

Background— The in vivo regeneration capacity of decellularized heart valve grafts is still controversial. The aim of this study was to evaluate function, morphological changes, and cellular composition of decellularized versus re-endothelialized ovine pulmonary valves (PV) after implantation into lambs for 1 or 3 months. Methods and Results— PV (n=21) were decellularized using detergents. Twelve PV were repopulated with autologous jugular veins endothelial cells (ECs) in a dynamic pulsatile bioreactor under simulated physiological conditions. Morphological evaluation before implantation included histological stainings (H&amp;E, Movat-pentachrome, von-Kossa, DAPI), immunostainings (anti-perlecan, anti-eNOS, anti-procollagen-I, anti-SM-α-actin), electron microscopy (EM), and DNA extraction. Decellularization led to cell-free scaffolds with preserved extracellular matrix (ECM) including basement membrane. Reseeded PV (n=5) were completely covered with ECs expressing endothelial nitric oxide synthase (eNOS) and von Willebrand factor (vWF). The function of orthotopically implanted decellularized and re-endothelialized PV (n=7, each) was analyzed after 1 and 3 months by echocardiography and revealed no differences in competence between both groups. A confluent EC monolayer expressing eNOS/vWF was only found in re-endothelialized PV but not in decellularized PV, whereas the valve matrices were comparable repopulated with interstitial cells expressing SM-α-actin and procollagen-I. More thrombotic and neointima formations were observed in decellularized PV. No signs of calcification were detected in both PV types. Conclusion— In vitro re-endothelialization of detergent-decellularized valves with autologous ECs under simulated physiological conditions significantly improves total EC valve coverage 3 months after implantation, whereas the valve repopulation with interstitial cells in vivo occurs most likely by cell migration inside the scaffold.
Inhibition of the Multidrug-Resistant Phenotype by Targeting YB-1 with a Conditionally Oncolytic Adenovirus: Implications for Combinatorial Treatment Regimen with Chemotherapeutic Agents
Authors: Klaus Mantwill, Nadia Köhler-Vargas, Alexandra Bernshausen, Alexa Bieler, Hermann Lage, Alexander Kaszubiak, Pavel Surowiak, Tanja Dravits, Uwe Treiber, Rudolf Hartung, Bernd Gansbacher, Per S. Holm
Journal: Cancer Research (2006)

Abstract Bearing in mind the limited success of available treatment modalities for the therapy of multidrug-resistant tumor cells, alternative and complementary strategies need to be developed. It is known that the transcriptional activation of genes, such as MDR1 and MRP1, which play a major role in the development of a multidrug-resistant phenotype in tumor cells, involves the Y-box protein YB-1. Thus, YB-1 is a promising target for new therapeutic approaches to defeat multidrug resistance. In addition, it has been reported previously that YB-1 is an important factor in adenoviral replication because it activates transcription from the adenoviral E2-late promoter. Here, we report that an oncolytic adenovirus, named Xvir03, expressing the viral proteins E1B55k and E4orf6, leads to nuclear translocation of YB-1 and in consequence to viral replication and cell lysis in vitro and in vivo. Moreover, we show that Xvir03 down-regulates the expression of MDR1 and MRP1, indicating that recruiting YB-1 to the adenoviral E2-late promoter for viral replication is responsible for this effect. Thus, nuclear translocation of YB-1 by Xvir03 leads to resensitization of tumor cells to cytotoxic drugs. These data reveal a link between chemotherapy and virotherapy based on the cellular transcription factor YB-1 and provide the basis for formulating a model for a novel combined therapy regimen named Mutually Synergistic Therapy. (Cancer Res 2006; 66(14): 7195-202)
Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. II. T lymphocyte-mediated cytolysis.
Authors: T Boon, J Van Snick, A Van Pel, C Uyttenhove, M Marchand
Journal: The Journal of Experimental Medicine (1980)

Tumor cell variants that were rejected by syngeneic mice (tum-) were obtained from mastocytoma P815 by mutagenesis (as described in the accompanying report (13). A considerable T lymphocyte-mediated lysis was observed upon incubation of these tum- variants with peritoneal exudate cells collected a few days after an intraperitoneal challenge of immune animals. Spleen cells from these animals were cytolytic after stimulation in vitro with the immunizing variant. New antigens, absent from the original P815 tum+ cells, were detected on 15 of the 21 tum- variants that were tested. All these antigens appeared to be different. No new antigen was detected on any of 10 mutagenized P815 clones that had retained their ability to form tumors. We compared the evidence obtained in vivo and in vitro for the presence of specific antigens on five tum- variants. Three variants were shown both in vivo and in vitro to carry an individual antigen. One showed no specificity either in vivo or in vitro. However, for one variant, no specificity was observed in vivo, although cytolysis tests demonstrated the existence of a singular antigenic specificity.
Vindesine in patients with metastatic malignant melanoma: a Southwest Oncology Group study.
Authors: J M Quagliana, R L Stephens, L H Baker, J J Costanzi
Journal: Journal of Clinical Oncology (1984)

A phase II study using vindesine (3 mg/m2 by slow intravenous push at seven to 14 day intervals) was carried out in 42 patients with metastatic melanoma. There was one complete remission (2.5%) of greater than 12 months duration; seven partial remissions (17.5%) of two, three, three, four, five, six and eight months duration; 11 with no change (27.5%) of one to 10 months duration; and 21 (52.5%) patients with increasing disease. Toxicity included neutropenia, neurotoxicity, phlebitis and cellulitis at the site of injection, alopecia, fever and chills, myalgias, and gastrointestinal toxicity. It was concluded that vindesine does have activity in some patients with metastatic malignant melanoma. Further studies in previously untreated patients are warranted.
Cytochrome <i>P</i>450 1B1 Is Overexpressed and Regulated by Hypomethylation in Prostate Cancer
Authors: Takashi Tokizane, Hiroaki Shiina, Mikio Igawa, Hideki Enokida, Shinji Urakami, Toshifumi Kawakami, Tatsuya Ogishima, Steven T. Okino, Long-Cheng Li, Yuichiro Tanaka, Norio Nonomura, Akihiko Okuyama, Rajvir Dahiya
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cytochrome P450 1B1 (CYP1B1), a dioxin inducible member of the CYP supergene family, is overexpressed in various human malignancies including prostate cancer. We hypothesized that promoter/enhancer CpG methylation contributes to the regulation of CYP1B1 expression in human prostate tissue. Experimental Design: Expression and induction of the CYP1B1 gene in clinical prostate tissues and prostate cancer cell lines were investigated. The methylation status of the CYP1B1 gene was analyzed in 175 prostate cancer and 96 benign prostatic hyperplasia samples using methylation-specific PCR (MSP) and bisulfite-modified DNA sequencing. MSP primers covered dioxin response elements (DRE) and Sp1 sites that are important for the expression of CYP1B1. Results: Expressions of CYP1B1 mRNA and protein were increased in prostate cancer. The aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) heterodimer complex activates gene transcription by binding to the DREs of CYP1B1. In prostate cancer cells, CYP1B1 mRNA was induced by 2,3,7,8-tetrachlorodigenzo-p-dioxin (TCDD) and/or demethylation agent (5-aza-2-deoxycytidine). There was no change in the expressions of AhR and ARNT. Methylation of promoter/enhancer regions was significantly higher in benign prostatic hyperplasia compared with prostate cancer. MSP-positive patients had significantly lower risk for prostate cancer as compared with MSP-negative patients. There was no correlation between CYP1B1 methylation status and clinicopathologic features. Conclusions: CYP1B1 is overexpressed in prostate cancer and regulated by hypomethylation of its promoter/enhancer region. This is the first report about CYP1B1 regulation in human clinical prostate samples showing that hypomethylation of the CYP1B1 gene may play an important role in prostate cancer.
Aetiology and classification of adenocarcinoma of the gastro-oesophageal junction/cardia
Authors: K. E. L. McColl, J. J. Going
Journal: Gut (2010)

<h3>Background/purpose</h3> Carotid body paragangliomas are rare hypervascular lesions which may benefit from preoperative devascularization to reduce intraoperative blood loss. The optimal method for devascularization of these tumors is not known. Our purpose was to evaluate the extent of angiographic devascularization and intraoperative blood loss using only ethylene vinyl alcohol copolymer (EVOH) for percutaneous glomus tumor embolization. <h3>Methods</h3> A consecutive series of seven paragangliomas located at the carotid bifurcation were treated with percutaneous embolization with EVOH as the sole embolic agent. <h3>Results</h3> Complete devascularization of seven paragangliomas was achieved in all cases percutaneously with only EVOH. There were no complications. The average intraoperative blood loss was 55 ml (range 15–80 ml). <h3>Conclusions</h3> Our preliminary experience suggests that EVOH may offer a higher degree of devascularization when compared with other embolic agents. This may facilitate easier surgical resection with lower blood loss. EVOH seems to be safe when percutaneously injected as the sole embolic agent.
Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus
Authors: Olaf Beck, Max S. Topp, Ulrike Koehl, Emmanuel Roilides, Maria Simitsopoulou, Mitra Hanisch, Jacqueline Sarfati, Jean Paul Latgé, Thomas Klingebiel, Hermann Einsele, Thomas Lehrnbecher
Journal: Blood (2005)
Epidermal Growth Factor–Independent Transformation of Ba/F3 Cells with Cancer-Derived Epidermal Growth Factor Receptor Mutants Induces Gefitinib-Sensitive Cell Cycle Progression
Authors: Jingrui Jiang, Heidi Greulich, Pasi A. Jänne, William R. Sellers, Matthew Meyerson, James D. Griffin
Journal: Cancer Research (2005)

Abstract Epidermal growth factor receptor (EGFR) plays critical roles in many biological processes and in tumorigenesis. Here, we show that two mutated EGFRs found in lung and other malignancies, EGFR-G719S and EGFR-L858R, could transform Ba/F3 cells to interleukin-3 (IL-3)–independent growth, in a ligand-independent manner, an activity associated with the transforming function of other mutated tyrosine kinases. The mutated receptors are autophosphorylated in the absence of IL-3 without EGF stimulation, and their expression led to the constitutive activation of signal transducers and activators of transcription 5, extracellular signal-regulated kinase 1/2 (ERK1/2), ERK5, and AKT. In wild-type EGFR-expressing Ba/F3 cells, the major EGF-mediated signaling pathways were still intact. Gefitinib inhibited the growth of mutant EGFR-transformed Ba/F3 cells. Strikingly, the gefitinib sensitivity of cells expressing the L858R mutant was significantly greater than that of cells expressing the G719S mutant form, suggesting that distinct EGFR mutations may be differentially sensitive to small-molecule inhibitors. Furthermore, our data showed an antiproliferative effect of gefitinib on the EGFR-transformed Ba/F3 cells. Our results provide a model system to study the function of mutated EGFR and the differential effects of pharmacologic EGFR inhibition on the distinct mutant forms of this tyrosine kinase.
Reversal of Antiparkinsonian Drug Toxicity by Physostigmine: A Controlled Study
Authors: M. KHALED EL-YOUSEF, DAVID S. JANOWSKY, JOHN M. DAVIS, H. JOSEPH SEKERKE
Journal: American Journal of Psychiatry (1973)

Three female schizophrenic patients receiving a combination of psychotropic agents, including the antiparkinsonian agent benztropine mesylate, developed the central anticholinergic syndrome, consisting of hallucinations, anxiety, short-term memory loss, disorientation, and agitation. These symptoms responded dramatically to physostigmine salicylate administered intramuscularly; they were unaffected by placebo injection given on a double-blind basis. In patients receiving multiple psychotropic drugs, evaluation of whether the patient is acting confused because of the combined central anticholinergic properties of these drugs is important. When identified, this syndrome can usually be treated by reduction of the dose of the anticholinergic agents or in special instances by the use of the cholinomimetic agent physostigmine.