tbuckley/cabot-search huggingface dataset:
Effect of Total-Body X Radiation from Near-Threshold to Tissue-Lethal Doses on Small-Bowel Epithelium of the Rat. II. Changes in Nucleic Acid and Protein Synthesis in Relation to Cell Division
Authors: Toal Jn, Reid Jc, Williams Rb, White J
Journal: JNCI Journal of the National Cancer Institute (1958)

Effect of Total-Body X Radiation from Near-Threshold to Tissue-Lethal Doses on Small-Bowel Epithelium of the Rat. II. Changes in Nucleic Acid and Protein Synthesis in Relation to Cell Division Get access Jane Nicolet Toal, Jane Nicolet Toal Laboratory of Physiology, National Cancer Institute,2 and Pathology Division, Naval Medical Research Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar James C. Reid, James C. Reid Laboratory of Physiology, National Cancer Institute,2 and Pathology Division, Naval Medical Research Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Bland Williams, R. Bland Williams Laboratory of Physiology, National Cancer Institute,2 and Pathology Division, Naval Medical Research Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Julius White Julius White Laboratory of Physiology, National Cancer Institute,2 and Pathology Division, Naval Medical Research Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 21, Issue 1, July 1958, Pages 63–76, https://doi.org/10.1093/jnci/21.1.63 Published: 01 July 1958 Article history Received: 14 November 1957 Published: 01 July 1958
Relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab
Authors: P.P.M. van Lümig, R.J.B. Driessen, M.A.M.A. Roelofs-Thijssen, J.B.M. Boezeman, P.C.M. van de Kerkhof, E.M.G.J. de Jong
Journal: British Journal of Dermatology (2011)

Guidelines concerning biological treatment of patients with psoriasis recommend different pretreatment and monitoring laboratory panels in variable frequencies to monitor treatment.To investigate the relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab.A prospective cohort study over 5 years was conducted in all consecutive patients with psoriasis on etanercept or adalimumab. All laboratory investigations performed for monitoring treatment were analysed. Laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events v4.03. The primary endpoint was the percentage of patients with a grade 3 or grade 4 laboratory abnormality. The secondary endpoints were defined as: (i) significant changes in laboratory parameters during etanercept or adalimumab treatment and (ii) the percentage of patients having a laboratory abnormality requiring discontinuation of etanercept or adalimumab treatment.Laboratory parameters were available for 162 patients treated with etanercept and/or adalimumab. The number of treatment episodes was 155 for etanercept and 58 for adalimumab. Follow-up was 316 patient-years for etanercept and 54 patient-years for adalimumab. Thirty-eight of 146 patients treated with etanercept (26%) had one or more grade 3 and/or grade 4 laboratory abnormalities. For adalimumab, this was eight of 58 (14%). These were predominantly considered unrelated to biologic therapy. For both biologics, significant changes were observed in mean laboratory parameters during treatment compared with pretreatment as well as significant trends. However, mean values during treatment remained within normal ranges. Laboratory abnormalities did not lead to permanent discontinuation of biologic treatment in any patient.In this cohort, the incidence of biologic therapy-related serious laboratory abnormalities was low. Our findings do not support a need for routine laboratory testing in patients with psoriasis on etanercept or adalimumab beyond the laboratory testing required for concomitant therapies or comorbidities.
In vitro and in vivo interaction of 64Cu-DOTA-cetuximab and epidermal growth factor receptor in cervical cancer cell lines
Authors: Laura A. Meyer, Martin Eiblmaier, Mark A. Watson, Linda J. Pike, Paula M. Fracasso, Carolyn J. Anderson
Journal: Clinical Cancer Research (2006)

B12   Cetuximab (ImClone Systems/Bristol-Myers Squibb), a chimeric monoclonal antibody specific for the extracellular domain of the human epidermal growth factor receptor (EGFR), is approved by the FDA for the treatment of EGFR-expressing, metastatic colorectal carcinoma. Patients treated with cetuximab show an objective response rate of 10.8%, and thus far, no correlation has been found between the degree of EGFR expression and the response to cetuximab treatment. At least 60% of cervical cancers are EGFR positive. Copper-64-labeled cetuximab and cervical cancer cell lines with varying degrees of EGFR expression were used to investigate characteristics of the antibody-EGFR interaction that might correlate with patient response. Five cervical cancer cell lines (C-33A (negative for EGFR), HeLa, DoTc2 4510, ME-180 and CaSki ) were shown by GeneChip microarray analysis to have different EGFR expression. Cetuximab was conjugated with the chelator DOTA and radiolabeled with  64 Cu (T 1/2  = 12.7 h; β +  (17.4%)). Saturation receptor binding and internalization assays were carried out in the five cell lines using whole cells with  64 Cu-DOTA-cetuximab and receptor densities (B max ) and binding constants (K d ) were determined. The values for EGFR binding affinity (K d ) of  64 Cu-DOTA-cetuximab in the five cell lines were very similar (0.1 - 0.7 nM), as was expected for the same substrate-receptor interaction. The EGFR receptor concentration (B max ; fmol/mg total cellular protein) was found to mimic the order of EGFR expression as determined by microarray analysis and was in the order of CaSki (2133) > ME-180 (818) > DoTc2 4510 (610) > HeLa (305) > C-33A (24). The level of internalization of  64 Cu-DOTA-cetuximab by these cell lines showed the same trend, and studies are currently underway to examine the rate of internalization for each of the cell lines. CaSki cells were implanted into SCID mice and the resulting tumors were imaged by microPET with  64 Cu-DOTA-cetuximab. High uptake was observed in the CaSki tumors by both microPET imaging and biodistribution (SUV: 1.36; 13.2 ∓ 2.7 %ID/g). PET imaging of EGFR positive tumors with  64 Cu-DOTA-cetuximab may give further insight into the actions of cetuximab on EGFR positive tumors.
Induction of myeloid cells with suppressive activity by human tumor-released microvesicles
Authors: Licia Rivoltini, Roberta Valenti, Paola Filipazzi, Veronica Huber, Paola Canese, Lorenzo Pilla, Giorgio Parmiani
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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We recently demonstrated that human tumors, such as melanoma and colo-rectal cancer, release microvesicles (MV) expressing bioactive FasL and TRAIL molecules which induce apoptosis in activated anti-tumor T cells (Andreola et al, J Exp Med 2002; Huber et al. Gastroenterology 2005 ). We additionally showed that MV with comparable phenotypic and functional features can be found in tumor lesions and sera from cancer patients, suggesting a role of this pathway in tumor progression. Here we report that tumor-released MV can profoundly affect myeloid cell function by inducing an abnormal differentiation which results in the generation of suppressive cells. Indeed, when CD14+ monocytes are differentiated into DC (by culture with GM-CSF and IL-4) in the presence of tumor-released MV, they retain CD14 expression and significantly down-modulate co-stimulatory molecules, such as CD80 and CD86. Most importantly, these CD14+ cells become HLA-DRneg/low and secrete relevant amounts of TGFβ, which exert a potent suppressive activity on lymphocyte proliferation. Notably, the same CD14+HLA-DRneg/low TGFβ-secreting cells were generated in vitro when monocytes were differentiated in the presence of MV isolated from the plasma of advanced melanoma patients. Therefore, we searched for the presence of CD14+HLA-DRneg cells in the peripheral blood of melanoma patients, where the frequency of these cells appeared significantly higher as compared to healthy donors. CD14+HLA-DRneg cells directly isolated from the peripheral blood of melanoma patients spontaneously secreted higher levels of TGFβ as compared to CD14+HLA-DR+ cells and displayed potent suppressive activity on lymphocyte proliferation. Finally, CD14+HLA-DRneg cells with an enhanced suppressive activity were significantly expanded in the same melanoma patients after treatment with HSP96 vaccine and GM-CSF, a growth factor that seems to be involved also in myeloid suppressor cell function. Altogether, our findings show that human tumor cells can induce the generation of myeloid cells with suppressive activity by releasing MV that can exert a long-distance systemic effect, without the need of cell-to-cell contact. These cells, which are expanded in the peripheral blood of melanoma patients, are likely to play a detrimental role in the immunological and clinical efficacy of anti-tumor vaccines.
Mature results of MM‐011: A phase I/II trial of liposomal doxorubicin, vincristine, dexamethasone, and lenalidomide combination therapy followed by lenalidomide maintenance for relapsed/refractory multiple myeloma
Authors: Aleksandr Lazaryan, Mohamad A. Hussein, Frederic J. Reu, Beth Faiman, Becky Habecker, Mary Ann Karam, Janice Reed, Kimberly Hamilton, Joel Waksman, Kellie Bruening, Gordan Srkalovic, Steven Andresen, Matthew Kalaycio, John W. Sweetenham, Ronald Sobecks, Robert Dean, Robert Knight, Jerome B. Zeldis, Rachid Baz
Journal: American Journal of Hematology (2013)

A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1). After 4-6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1-7); 49 (64.5%) patients had refractory disease. Forty-three (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respectively. Four (5.3%) treatment-related deaths occurred during induction. Responses were seen in 53.0% (at least partial response) and 71.2% (at least minor response) of patients. Overall, median progression-free survival and overall survival were 10.5 and 19.0 months, respectively; in patients with refractory disease these values were 7.5 and 11.3 months, respectively. Lenalidomide with anthracycline-based chemotherapy followed by maintenance lenalidomide provided durable control in patients with RRMM (ClinicalTrials.gov number, NCT00091624).
Brief Communication: Alkaline Phosphatase Activity in Hyperplastic and Neoplastic Urinary Bladder Epithelium of Mice Fed 2-Acetylaminofluorene
Authors: Benjamin Highman, Charles H. Frith, Neil A. Littlefield
Journal: JNCI Journal of the National Cancer Institute (1975)

Studies were made on the urinary bladder of 66 BALB/c mice of both sexes; 21 were fed a normal diet and 45, a diet containing 100-500 parts per million (ppm) of 2-acetylaminofluorene (2-AAF). Bladder epithelial hyperplasia was noted in 22 of 24 mice given 2-AAF for 7 months and in 20 of 21 given 2-AAF for 19 months. Transitional cell carcinomas were in 12 of 21 mice given 2-AAF for 19 months and in all except the 9 females given the low dose (100 ppm). Special stains revealed marked alkaline phosphatase activity in the bladder epithelium of untreated controls and slightly to moderately reduced activity in the hyperplastic epithelium, particularly the lower layers, of mice given 2-AAF for 7 months. Activity was markedly reduced and confined largely to the upper layers in mice treated for 19 months. The transitional cell carcinomas showed no activity except focally in a few tumor masses in 11 of 12 mice with tumors. Alkaline phosphatase activity was usually slightly to moderately increased in the sub-epithelial stroma after 7 months' treatment with 2-AAF and markedly increased after 19 months. Loss of alkaline phosphatase activity in the bladder epithelium may be a preneoplastic change.
How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA2LEN statement
Authors: J. Bousquet, H. J. Schünemann, P. J. Bousquet, C. Bachert, G. W. Canonica, T. B. Casale, P. Demoly, S. Durham, K.-H. Carlsen, H.-J. Malling, G. Passalacqua, F. E. R. Simons, J. Anto, C. E. Baena-Cagnani, K.-C. Bergmann, T. Bieber, A. H. Briggs, J. Brozek, M. A. Calderon, R. Dahl, P. Devillier, R. Gerth van Wijk, P. Howarth, D. Larenas, N. G. Papadopoulos, P. Schmid-Grendelmeier, T. Zuberbier
Journal: Allergy (2011)

To cite this article: Bousquet J, Schünemann HJ, Bousquet PJ, Bachert C, Canonica GW, Casale TB, Demoly P, Durham S, Carlsen K-H, Malling H-J, Passalacqua G, Simons FER, Anto J, Baena-Cagnani CE, Bergmann K-C, Bieber T, Briggs AH, Brozek J, Calderon MA, Dahl R, Devillier P, Gerth van Wijk R, Howarth P, Larenas D, Papadopoulos NG, Schmid-Grendelmeier P, Zuberbier T. How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA2LEN statement. Allergy 2011; 66: 765–774. Abstract Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom–medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.
37. Duration of Immunologically Detectable AAV-2 Capsid in an Animal Model
Authors: Denise E. Sabatino, Federico Mingozzi, David C. Brooks, Alex Schlachterman, Shyrie Edmonson, Linda Couto, Peter Colosi, Haifeng Chen, Hildegund C. J. Ertl, Katherine A. High
Journal: Molecular Therapy (2004)

In a Phase I trial for Hemophilia B six subjects underwent infusion of an adeno-associated viral (AAV) vector expressing human Factor IX (F.IX) under the control of a liver specific promoter. One subject in the high dose cohort (5×10e12 vg/kg) attained therapeutic F.IX levels in the range of 5-12% for 5 wks after vector infusion, but these declined to baseline ( 1 week but <4 wks after rAAV-2 vector injection. This mouse model will allow further investigation of the effectiveness of transient immune suppression at the time of vector administration and for the period surrounding immunologic persistence of capsid proteins.
Abstract 101: Top Quality of Ventilation During Out-of-Hospital Cardiac Arrest Is Hard to Reach
Authors: Philip Datler, Patrick Sulzgruber, Michael Poppe, Markus Keferböck, Sebastian Zeiner, Elisabeth Lobmeyr, Alexander Nürnberger, Raphael Van Tulder, Mario Krammel, Fritz Sterz
Journal: Circulation (2014)

INTRODUCTION: With an incidence of ~45patients with out-of hospital cardiac arrest (OHCA) /100.000 inhabitants per year and thus over 700 cases annually, but a survival rate as low as 10%, OHCA remains still a challenge the chain of survival. Recently ventilation has gained less importance for BLS and thus the question arises, if this attitude was mirrored during ALS measures provided by ambulance crews. Therefore our analysis assessed the quality of ventilation during out of hospital cardiac arrests. METHODS: Over a period of 9 months, from August 1st 2013 until April 30th 2014, all patients suffering from an OHCA, aged 18 years and above and treated by the emergency medical service crews in Vienna, Austria were included in this study. A collective of 701 consecutive cases have been analyzed using the ECG- and impedance data recorded by the defibrillators used. On the basis of this data, the abidance of the quality standards of ventilation was examined using the current guidelines of the European Resuscitation Council of 2010 as gold standard. After the evaluation of each case, the responding EMS-teams were informed about the quality of the resuscitation via a feedback form. RESULTS: Endotracheal intubation was accomplished in 338 patients (47%). Ventilation was performed in accordance to the ERC guidelines in 49% (CI: 46-52) of total recorded ventilation minutes. Patients who had restoration of spontaneous circulation (ROSC) (n=135) after being intubated were ventilated with 9 (CI: 9-11; variance: 11) ventilations per minute. In patients not achieving ROSC (n=203) 10 (CI: 9-11; variance: 25) ventilations per minute were administered. Patients that were ventilated with a supraglottic airway device or a bag valve and mask received 6(SD±4) ventilations per minute. CONCLUSION: The high ventilation rate standard deviations within the compliance to guidelines suggest that there are numerous cases in which ventilation standards are not met. Therefore further analysis will be necessary to find out, what influence this might have on outcome and if it will be necessary to put more emphasis in upcoming discussions on the quality of ventilation at least during advanced life support.
Abstract 14939: Deficiency of Fatty Acid Binding Protein-4 and -5 Impairs Intestinal Lipid Absorption
Authors: Mas R Syamsunarno, Tatsuya Iso, Masahiko Kurabayashi
Journal: Circulation (2014)

Introduction:  Fatty acid binding protein 4 (FABP-4) and FABP-5 are cytosolic FA chaperones that mediate metabolic disorders such as diet-induced obesity, diabetes and atherosclerosis. We recently showed that FABP4/5 expressed in capillary endothelial cells facilitate FA uptake from circulation into interstitial fluid. However, serum levels of free FA (FFA) and triacylglycerol (TG) were not elevated in mice lacking both FABP4/5 (double knockout: DKO) compared with wild-type (WT) during feeding despite the fact that FA uptake by the heart and skeletal muscle was significantly reduced in DKO mice.   Hypothesis:  FABP4/5 also play a role in lipid absorption.   Results:  Under high fat diet for six weeks as well as ketogenic diet with no carbohydrate for three days, serum TG levels were significantly lower in DKO mice compared to WT, suggesting reduced lipid absorption during long term lipid overload. We next examined an effect of acute lipid overload by olive oil gavage (10 μl/g body weight). Serum TG levels were significantly lower in DKO mice at 2, 4 and 6 hours after olive oil gavage, which was accompanied by reduced levels of TG-rich lipoproteins, chylomicron and very large density lipoprotein, as well as TG levels in intestinal lymph. Lower levels of TG by olive oil gavage were confirmed in DKO mice even when TG consumption by peripheral tissues was blocked by intravenous injection of tyloxapol, an inhibitor of lipoprotein lipase. Furthermore, TG accumulation in proximal small intestine was diminished, suggesting that lipid absorption may be inhibited at levels of FA uptake and/or TG formation. Consistent with this, expression level of diacylglycerol acyl-transferase 2, a gene involved in TG formation, was decreased. Curiously enough, immunohistochemistry revealed that FABP4/5 were expressed in capillary endothelial cells in villi of small intestine, but not lymph vessel, where TG-rich chyromicron is secreted, suggesting that FABP4/5 play a role in intestinal lipid absorption through unexpected mechanism.   Conclusions:  Lipid absorption is impaired in DKO mice, and raise the possibility that protection of DKO mice from high fat diet-induces metabolic abnormalities is at least partly ascribed to disturbance of lipid absorption.
Soft Tissue Pain and Disability
Authors: Rene Cailliet
Journal: Annals of Internal Medicine (1988)

Detailing medicolegal decisions involving soft tissue injuries, the expenses paid annually in personal injuries and workers' compensation, this volume includes recent references and augmentation of many recent concepts along with diagnostic and therapeutic interventions. Issues covered include: fibromyalgia syndromes, treatment modalities for soft tissue pain, reflex sympathetic dystrophy, psychological aspects of soft tissue pain and workers' compensation.
PARAPLEGIA CAUSED BY UNUSUAL EXTRADURAL GRANULOMA SIMULATING NEOPLASM: PRESENTATION OF A CASE WITH COMPLETE RECOVERY FOLLOWING SURGICAL REMOVAL
Authors: R W ARD
Journal: Annals of Internal Medicine (1957)

Case Reports1 April 1957PARAPLEGIA CAUSED BY UNUSUAL EXTRADURAL GRANULOMA SIMULATING NEOPLASM: PRESENTATION OF A CASE WITH COMPLETE RECOVERY FOLLOWING SURGICAL REMOVALROBERT W. ARD, M.D.ROBERT W. ARD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-46-4-808 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe common causes of extradural tumors include such well known pathologic entities as meningioma, neurofibroma, osteogenic sarcoma, hemangioma, cystic lesions (idiopathic, dermoid, epidermoid and parasitic), chondroma, osteoma, giant cell tumor, melanoma, lympho-epithelioma, Hodgkin's disease, leukemia, metastatic carcinoma, and abscesses of tuberculous or pyogenic nature. However, close scrutiny of the literature fails to reveal any mention of granulomata, either proved or suspected of being sarcoid, as etiologic possibilities in the differential diagnosis of extradural growths that may produce spinal cord compression with secondary paraplegia. It is the purpose of this paper to report a case in which such an extradural granuloma...Bibliography1. Colover J: Sarcoidosis with involvement of the nervous system, Brain 71: 451 (Mar.) 1948. CrossrefMedlineGoogle Scholar2. Aszkanazy CL: Sarcoidosis of the central nervous system, J. Neuropath. and Exper. Neurol. 11: 392, 1952. CrossrefGoogle Scholar3. IsraelSones HLM: The diagnosis of sarcoidosis with special reference to the Kveim reaction, Ann. Int. Med. 48: 1269 (Dec.) 1955. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Perry Point, Maryland*Received for publication May 9, 1956.From the Medical Service, U. S. Veterans Hospital, Perry Point, Maryland.Requests for reprints should be addressed to Robert W. Ard, M.D., U. S. Veterans Hospital, Perry Point, Maryland. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1957Volume 46, Issue 4Page: 808-814KeywordsGranulomasLymphocytic leukemiaMedical servicesMelanomaParaplegiaProteinsSarcoidosisSarcomaSpinal cordTuberculosis ePublished: 1 December 2008 Issue Published: 1 April 1957 PDF downloadLoading ...