tbuckley/cabot-search huggingface dataset:
Abstract 5386: Therapeutic efficacy of RMLV vectors in human and murine glioma models
Authors: Akihito Inagaki, Kei Hiraoka, Christopher R. Logg, Shuichi Kamijima, Derek Ostertag, Omar D. Perez, Harry E. Gruber, Douglas J. Jolly, Joan M. Robbins, Noriyuki Kasahara
Journal: Cancer Research (2011)

Abstract Unique among replicating viruses being developed as oncolytic agents, replicating murine leukemia virus (RMLV) retroviruses propagate without immediate lysis of host cells and maintain viral persistence through stable integration. Due to its intrinsic inability to infect quiescent post-mitotic cells and susceptibility to innate antiviral defenses that exist in normal cells but are inactivated in many cancers, RMLV vector replication has been shown to be highly tumor-selective. We have previously demonstrated that RMLV vectors are capable of highly efficient replication in tumor cells, and we have found significantly enhanced survival benefit in a variety of cancer models in vivo when RMLV vectors are employed for delivery of prodrug activator genes such as yeast cytosine deaminase (yCD), which mediates the conversion of inactive prodrug 5-fluorocytosine (5FC) to the anti-cancer drug, 5-fluorouracil (5FU). In the present study, we tested a newly developed RMLV vector with modified virus backbone sequences and a codon-optimized yCD gene (Toca511). First, we examined in vitro cytotoxicity using human (U87) and murine (TU-2449) glioma cell lines by MTS assay. The cell viability of Toca511-transduced cells was reduced by &amp;gt;80% after 5 or 8 days of exposure to the prodrug, respectively. Second, we examined the therapeutic efficiency of this newly developed vector in subcutaneous U87 human glioblastoma models and TU2449 syngeneic mouse models. Toca511-mediated prodrug activator therapy strongly inhibited tumor growth in both subcutaneous models. Third, therapeutic efficacy was evaluated, and the minimum effective doses of 5FC prodrug and Toca511 vector determined in an intracranial U87 xenograft model. Systemic administration of 5FC resulted in significant inhibition of bioluminescent signals in mice whose tumors had been infected with Toca511 but not in control mice, associated with significant survival benefit even after injecting only 1×1e3 total vector units (p=0.0015). These data suggest that we have been successful in developing an improved retrovirus vector that shows strong therapeutic efficacy when used for prodrug activator gene therapy in both subcutaneous and intracranial xenograft models of human and/or murine glioma. This vector has now entered Phase I/II clinical trials for glioblastoma. Now, with the use of RMLV vectors such as Toca511, the original promise of retrovirus-mediated gene therapy strategies for cancer may finally be fulfilled. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5386. doi:10.1158/1538-7445.AM2011-5386
Education and prevalence of Alzheimer's disease and vascular dementia
Authors: R. O'Carroll, K. Ebmeier
Journal: BMJ (1995)

driven by their evangelical belief that the ills of renal bone disease are best treated by calcium and the avoidance of derivatives of vitamin D.2 It is unfortunate that their conclusions are based on their experience-a notorious arbiter of efficacyrather than on double blind and randomised controlled studies, but they raise some important points.The transient suppression of hyperparathyroidism with alfacalcidol and the subsequent escape are well described, not only with derivatives of vitamin D but also with cholecalciferol and with calcium whether given in the form of supplements to the diet or supplements to the dialysis fluid.3As mentioned, the regimen that we used did not adversely affect serum phosphate concentration.This suggests that factors other than hyperphosphataemia, vitamin D metabolites, and extracellular calcium concentrations are important components of the pathogenesis of hyperparathyroidism.Higher doses of alfacalcidol than we gave may possibly have more complete or long lasting effects.The view that alternative treatment regimens would provide more complete effects is a hypothesis that is not yet proved.Fournier and colleagues also raise the question of whether our patients had a dietary deficiency of vitamin D. Bone histology is the ultimate arbiter of osteomalacia, which was rarely found on biopsy before treatment: only one patient had osteo- malacia in the absence of osteitis fibrosa on histological examination of bone.Dietary intakes of calcium and vitamin D (which were measured but not given in our paper) were well above the recommended daily allowance, and the average dietary intake of calcium exceeded 800 mg daily.If data from all patients with prevalent osteomalacia are excluded the same results were observed.In response to other questions, reference ranges for bone cell counts vary according to the labora- tory.Our own are provided elsewhere.4The optimum range of parathyroid hormone concen- trations in early renal failure is provided by the reference ranges.We speculate that the same range will operate, irrespective of the degree of renal failure.
Impaired Production of Lymphokines and Immune (Gamma) Interferon in the Acquired Immunodeficiency Syndrome
Authors: Henry W. Murray, Berish Y. Rubin, Henry Masur, Richard B. Roberts
Journal: New England Journal of Medicine (1984)

To examine the cellular immune defect that predisposes patients with the acquired immunodeficiency syndrome (AIDS) to opportunistic infections, we tested T lymphocytes from 16 patients for the capacity to secrete macrophage-activating products (lymphokines) including gamma interferon. Mononuclear cells from 10 of 11 patients did not generate an effective lymphokine in response to mitogen, and 11 of 16 produced subnormal levels of gamma interferon (less than 300 U per milliliter). In addition, upon stimulation with specific microbial antigen, cells from none of 14 patients generated active lymphokines, and cells from 13 to 14 completely failed to secrete gamma interferon. However, the antimicrobial function of monocytes from the patients was intact, and once stimulated with normal lymphokines or gamma interferon alone, macrophages derived from patients' monocytes responded with enhanced and effective intracellular antimicrobial activity. These results suggest that impaired lymphokine production may predispose patients with AIDS to opportunistic infections, and they provide a rationale for using gamma interferon as immunotherapy.
1081 VARIABLES PREDICTING SUSTAINED VIRAL RESPONSE (SVR) IN RETREATMENT OF HCV INFECTION AFTER LIVER TRANSPLANTATION (LT). NO EFFECT OF CALCINEURIN INHIBITOR (CNI) SWITCH
Authors: V. Aguilera, B. Roche, L. Navarro, A. Rubín, J.-C. Duclos-Vallee, M. Prieto, D. Samuel, M. Berenguer
Journal: Journal of Hepatology (2012)
Is the Change of Integrin αvβ3 Expression in the Infarcted Myocardium Related to the Clinical Outcome?
Authors: Yaping Luo, Yi Sun, Zhaohui Zhu, Fang Li
Journal: Clinical Nuclear Medicine (2014)

Two adult male patients with myocardial infarction underwent Ga-BNOTA-PRGD2 (arginine-glycine-aspartic acid [RGD]) PET/CT scans. The initial images that were acquired within 1 week after the cardiac event showed RGD retention in the infarcted regions in both patients. At follow-up Ga-BNOTA-PRGD2 PET/CT scans, RGD uptake was again noticed in the infracted region in the patient who was still had symptoms. However, in the patient who had become asymptomatic, RGD uptake in the infarcted region was no longer visualized.
Contrast enhancement during endosonography to diagnose autoimmune pancreatitis
Authors: Y. Ustundag, E. Alper, M. Eloubeidi
Journal: Endoscopy (2011)

We read with interest the article by Hocke et al. about the use of contrast-enhanced endosonography (CE-EUS) in the diagnosis of autoimmune pancreatitis (AIP) [1]. In this study, the authors examined 10 patients with AIP and five patients with pancreatic cancer and compared CE-EUS findings in both groups. Final diagnosis was achieved by either histology or cytology with immunostaining of immunoglobulin (Ig) G4 antibody. The authors reported that CE-EUS revealed net-like hypervascularization in 90 % of the cases with AIP and hypovascular lesions in cases of pancreatic carcinoma.
PWE-097 Classification of pseudomyxoma peritonei as low or high grade according to the WHO criteria is prognostically significant
Authors: N Carr, B Moran, T Cecil, K Chandrakumaran, I C Ilesley, A Mirnezami, F Mohamed
Journal: Gut (2012)

<h3>Introduction</h3> The current WHO classification of tumours of the digestive system divides pseudomyxoma peritonei into two grades, namely low-grade and high-grade. This study was designed to correlate survival with low-grade and high-grade pseudomyxoma peritonei classified according to the WHO criteria. <h3>Methods</h3> The histological slides of 274 consecutive patients were reviewed and designated as either low-grade or high-grade. The patients had been referred for cytoreductive surgery. The grade of the pseudomyxoma was correlated with survival data using the Kaplan–Meier method with the log-rank (Mantel-Cox) test. <h3>Results</h3> 238 (87%) patients had low-grade lesions and 36 (13%) had high-grade lesions. The most common primary tumour was a low grade appendiceal mucinous neoplasm (231 cases, 84%). Seven patients who died within 30 days of their operation (a postoperative mortality of 2.6%) were excluded from survival analysis. Another patient was excluded because of incomplete survival data. The remaining 266 patients showed an overall 5-year survival of 63% in patients with low-grade pseudomyxoma peritonei and 23% in patients with high-grade pseudomyxoma peritonei (p&lt;0.001). Complete cytoreduction was achieved in 165 (60%) patients; the 5-year survival for low-grade and high-grade was 84% and 48% respectively in this group (p&lt;0.001). The median survival of patients who had complete cytoreduction was 7.7 years for low-grade and 2.8 years for high-grade (p&lt;0.001). <h3>Conclusion</h3> Histological classification of pseudomyxoma peritonei as low-grade or high-grade correlates with prognosis. This may identify a group who could benefit from further adjuvant therapy which is not generally advocated for appendiceal mucinous tumours. <h3>Competing interests</h3> None declared.
PC0007 Inflammatory low back pain features at primary care
Authors: L. Myasoutova, S. Lapshina, M. Protopopov, S. Erdes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Low back pain is among the most frequent reasons for seeking medical care. Low back pain (LBP) of inflammatory origin deserves special interest as it can be a manifestation of a spondyloarthropathy (SpA). If a patient presents with LBP, diagnostic algorithm is quite complex. <h3>Objectives</h3> To evaluate incidence and features of rheumatic diseases in patients with inflammatory LBP (ILBP). <h3>Methods</h3> All patients (65 patients, male - 55, female - 10, mean age 32±8,1 years) without define diagnosis and with ILBP according to ASAS criteria, who were referred to rheumatologist in Kazan municipal rheumatology center from October 2010 to April 2011, were included in the study. Work-up included physical examination, medical history, HLA-B27 detection, laboratory finings (ESR, CRP), X-ray of lumbar spine and sacroiliac joints, magnetic resonance imaging (MRI) of lumbar spine and sacroiliac joints, (1,5T, T1 and STIR). The number of patients with established diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), axial and peripheral spondyloartropathy (SpA) and reactive spondyloartropathy (ReSpA) were analysed. Mean duration of LBP was 3,3±1,4 years, mean VAS score of LBP was 54±14, BASDAI score - 4,1±1,2. HLA-B27 was detected in 42 patients, sacroiliitis (filfilling the radiologic criterion for AS) was found to be present in 17 patients. 35 patients had inflammatory lesions on MRI, 18 patients had peripheral arthritis. <h3>Results</h3> The following diagnoses were set up according to actual criteria: AS - 17 patients, PsA - 6 patients, ReSpA - 7 patients, axial SpA - 18, peripheral SpA - 2 patients. In 15 patients ILBP was the only clinical feature. <h3>Conclusions</h3> In 77% of cases ILBP was a manifestation of a form of SpA (including AS, PsA, ReSpA), requiring appropriate use of those criteria by primary care doctors for a timely diagnosis. Still, in a number o cases it can be the only clinical manifestation and patients do not fulfill criteria for any form of SpA. Those patients should be monitored closely. <h3>Disclosure of Interest</h3> None Declared
Evaluation multicentrique et prospective de la mucosectomie et polypectomie endoscopique colorectale sous aspirine (étude OPERA)
Authors: G Vanbiervliet, T Barrioz, P Bulois, B Nalet, C Subtil, S Chaussade, J Filippi, M Barthet, F Cholet, M Le Rhun, G Medinger, R Gincul, C Boustière, B Napoléon, H Lamouliatte, J Jezequel, K Barange, A Charachon, C Cellier, V Lépilliez, P Bichard, JC Saurin, T Ponchon
Journal: Endoscopy (2014)

Les récentes recommandations ESGE n'autorisent pas la poursuite de l'aspirine pour la réalisation d'une mucosectomie endoscopique (EMR). Les études de large effectifs, multicentriques et prospectives manquent dans le domaine. Le but de l'étude était d'évaluer le risque hémorragique des patients traités par EMR ou large polypectomie recto colique endoscopique en cas de prise au long cours et préventive d'aspirine.
Étude PACOME: quels sont les facteurs associés à une préparation colique insuffisante?
Authors: G Cadiot, S Chaussade, P Coulom, J Lapuelle, R Laugier, B Richard-Molard, T Ponchon, F Henri
Journal: Endoscopy (2011)

Introduction: Une préparation colique insuffisante est associée à 40% des échecs de la coloscopie; elle réduit le taux de détection des adénomes. Les facteurs associés à une préparation colique insuffisante sont mal connus.
PR1--a Monoclonal Antibody That Reacts With an Antigen on the Surface of Normal and Malignant Prostate Cells
Authors: I. Pastan, E. Lovelace, A. V. Rutherford, S. Kunwar, M. C. Willingham, D. M. Peehl
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : The principal treatment for prostate cancer is surgery; prostate cancer is resistant to the common anticancer drugs. The only useful therapy for metastases involves diminishing testosterone levels by orchiectomy or administration of drugs, either of which may increase survival time. One approach to prostate cancer treatment is to use a monoclonal antibody (MAb) to target cytotoxic substances to these cancer cells. The MAbs available either do not react uniformly with prostate cancer cells or react with normal tissues. Thus, a new MAb is needed. Purpose : The goal of this study was to isolate an MAb that reacts with an antigen present on the surface of prostate cancer cells. Methods : A strain of prostate cancer cells was isolated from a prostate cancer specimen, grown for 2–4 weeks in shortterm culture, and used to immunize BALB/c mice. Hybridomas were then prepared by using spleen cells from the immunized mice. One hybridoma produced an MAb (PR1) that reacted with prostate cancers. Results : MAb PR1 is an IgM k subtype that reacts uniformly with the surface of most (25 of 26) adenocarcinomas of the prostate. It also reacts with the surface antigen on normal prostate epithelial cells and on cells from benign prostatic hyperplasia. MAb PR1 reacts with a limited number of normal tissues including a subset of principal cells located in the collecting ducts of the kidney. Conclusion : We conclude that MAb PR1 reacts with a differentiation antigen present in normal prostate and that this antigen continues to be expressed on almost all adenocarcinomas of the prostate. Implications : This antibody may be useful for the diagnosis of or therapy for prostate cancer. [J Natl Cancer Inst 85: 1149–1154, 1993]
RELEASE OF MICROPARTICLES FROM NATIVE CORONARY ARTERIES AND SAPHENOUS VEIN GRAFTS IN PATIENTS WITH ELECTIVE STENT IMPLANTATION UNDER PROTECTION WITH AN ASPIRATION DEVICE
Authors: Theodor Baars, Patrick Horn, Philipp Kahlert, Christian Heiss, Ralf Westenfeld, Malte Kelm, Raimund Erbel, Gerd Heusch, Petra Kleinbongard
Journal: Journal of the American College of Cardiology (2015)
Abstract 5188: Lrig1, a cell surface negative regulator of ErbB1-4, marks both proliferative and quiescent intestinal stem cells and acts as a tumor suppressor
Authors: Yang Wang, Anne E. Powell, Yina Li, James R. Davenport, Jeffrey Franklin, Kevin M. Haigis, Robert J. Coffey
Journal: Cancer Research (2011)

Abstract Whether proliferative and quiescent intestinal stem cells coexist in normal and cancerous tissue is controversial. Due to heightened transcript expression in the intestinal epithelial stem cell compartment, detection in quiescent hair follicle stem cells and frequent loss in breast cancer, we hypothesized that Leucine-rich repeats and immunoglobulin-like domain protein 1 (Lrig1) would mark a novel population of intestinal stem cells and may be important for intestinal homeostasis and in cancer. To study this, we generated Lrig1-CreERT2/+; R26R-LacZ mice to study the role of Lrig1. One day after Lrig1-CreERT2/+; R26R-LacZ mice received a single injection of tamoxifen, 1-2 cells were labeled in the progenitor zone. Three months after injection, 10% of colonic crypts were entirely labeled and 8% of crypts contained singly labeled, non-proliferative, Lgr5-negative cells at the crypt-base. In a regenerative response to gut injury, these singly labeled cells proliferated and gave rise to clusters of labeled daughter cells, demonstrating the ability of these quiescent stem cells to become activated. Loss of Lrig1 resulted in heightened expression of ErbB1-3 in the normal intestine, duodenal adenomas and carcinoma, supporting a functional role for Lrig1 in the maintenance of intestinal epithelial homeostasis and its ability to act as a tumor suppressor. In addition, driving stochastic loss of Apc in Lrig1-expressing cells results in multiple, large distal colonic tumors and less frequent, smaller intestinal tumors, which are common features of human familial polyposis. In summary, we show that Lrig1, a cell surface negative regulator of ErbB1-4, marks both proliferative and quiescent intestinal stem cells and acts as a tumor suppressor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5188. doi:10.1158/1538-7445.AM2011-5188
CDKN2A LOSS IS ASSOCIATED WITH SHORTENED SURVIVAL IN INFILTRATING ASTROCYTOMAS BUT NOT OLIGODENDROGLIOMAS OR MIXED OLIGOASTROCYTOMAS
Authors: A. Perry, G. F. Reis, M. Pekmezci, H. M. Hansen, R. E. Marshall, T. Rice, J. F. Wiencke, M. R. Wrensch, K. M. Walsh, A. Perry
Journal: Neuro-Oncology (2014)

BACKGROUND: Infiltrating WHO grade II and III gliomas are devastating and difficult to treat neoplasms classified as astrocytoma (A2), oligodendroglioma (O2), oligoastrocytoma (OA2), or anaplastic astrocytoma (A3), oligodendroglioma (O3), and oligoastrocytoma (OA3). Anaplastic grade is critically dependent on the presence of mitoses (astrocytomas) or high mitotic activity (oligodendroglial tumors), with CDKN2A deletion considered the most common mechanism for associated cell cycle dysregulation. We therefore sought to determine if p16 loss by immunohistochemistry (IHC) or CDKN2A gene by fluorescence in situ hybridization (FISH) are associated with patient survival across histologic groupings after controlling for age, grade, and other molecular markers. METHODS: Adults (18 years of age) with infiltrating gliomas (grades II or III) were selected from the UCSF Adult Glioma Study (N = 157). The population consisted of 90 males (average age = 43.2) and 67 females (average age = 40.7). Isocitrate dehydrogenase (IDH) status (IDH1 and IDH2) was known for all cases. Histology and grade were as follows: 53 O2, 33 A2, 29 OA2, 20 O3, 15 A3, 7 OA3. CDKN2A FISH was performed using commercial probes and immunostains for p16 and MIB1 (Ki-67) were similarly performed using commercial antibodies. The end point for the analysis was overall survival, analyzed using Cox proportional hazards, stratified by tumor histology and with adjustment for sex, age, grade, and various tumor markers. A total of 61 events (deaths) were observed, and median follow-up time across all subjects was 6.4 years. RESULTS: After controlling for age, sex, and grade, CDKN2A deletion was associated with decreased survival in astrocytoma patients (P = 0.045; HR = 3.1; 95%CI = 1.03-9.2) but not in oligodendroglioma or oligoastrocytoma patients (P = 0.57 and P = 0.67, respectively). A strong inverse association between IDH mutation and CDKN2A deletion was observed in astrocytomas, and the association of CDKN2A deletion with survival was attenuated after controlling for IDH status (P = 0.34). Interestingly, CDKN2A loss was observed in 83% of IDH wild-type versus 33% of IDH-mutant astrocytomas (P = 0.029). CDKN2A loss was only weakly associated with decreased p16 expression (p = 0.09), and the p16 labeling index (LI) was not associated with outcome. There was also no clear association between CDKN2A deletion and MIB1 LI (P = 0.92). CONCLUSIONS: CDKN2A deletion by FISH is associated with shortened survival in astrocytoma patients, but not in patients with oligodendroglial tumors. The strong inverse association between IDH mutation and CDKN2A deletion suggests that CDKN2A status may have prognostic value in the clinical work-up of grade II and III astrocytoma patients. SECONDARY CATEGORY: n/a.
Unexpected Myocardial Uptake on Perfusion Lung Scan in the Hepatopulmonary Syndrome
Authors: PELIN DEMIRKALE, AYŜE MUDUN, LEVENT KARASULU, MUSTAFA ERELEL, SEMA CANTEZ
Journal: Clinical Nuclear Medicine (1999)

A 17-year-old patient with chronic noncirrhotic liver disease was evaluated for recent exertional dyspnea and fatigue. Physical examination revealed peripheral cyanosis and a murmur of 2/6 intensity at the mitral and mesocardiac areas. Blood gas analysis suggested a right-to-left shunt. Echocardiography revealed an intact septum. A perfusion lung scan with Tc-99m MAA was performed to evaluate right-to-left shunt. On the scan, in addition to the distribution of Tc-99m MAA in the brain and kidneys, intense myocardial uptake was seen. The patient had hepatopulmonary syndrome, which reflects the arterial hypoxemia that can occur in patients with chronic liver disease.
Case 4-2014
Authors: Daniel P. Hunt, Victorine V. Muse, Amy Ly
Journal: New England Journal of Medicine (2014)

A 39-year-old man with a history of psoriasis was admitted to the hospital because of night sweats and abdominal pain. Imaging studies showed numerous ill-defined, hypoattenuating lesions in the spleen and mediastinal and hilar lymphadenopathy.