tbuckley/cabot-search huggingface dataset:
881. Preclinical Safety Assessment of Intra-Articular Administration of rAAV-humanTNFR:Fc in Rats in Support of a Phase I Arthritis Trial
Authors: Laurie M. Tatalick, Linda D. Wilson, Tara L. Allen, Dana B. Martin, Pervin Anklesaria
Journal: Molecular Therapy (2004)

Tumor Necrosis Factor α (TNFα) is a pivotal cytokine responsible for joint damage in inflammatory arthridites. Systemic inhibition of TNFα by anti-TNFα therapeutics provides marked therapeutic benefit to arthritic patients. However, systemic delivery can carry risks of immunosuppression and does not always provide complete relief to all affected joints. Previous animal studies have demonstrated therapeutic efficacy of local delivery of a recombinant adeno-associated viral serotype 2 vector (AAV) encoding for the rat tumor necrosis factor receptor (TNFR)-immunoglobulin (IgG1) Fc fusion protein (ratTNFR:Fc) in a rat arthritis model. Based on this efficacy data, the homologous human vector, rAAV-human TNFR:Fc, was assessed for safety and expression in support of a Phase I clinical trial. Five groups of Lewis rats received either vehicle, rAAV-ratTNFR:Fc or one of three different doses of rAAV-humanTNFR:Fc by intra-articular injection into both the left and the right tibial-tarsal joints. Five animals/sex/group were sacrificed on Study Day 31 and an additional 3 animals/sex from the vehicle and high dose rAAV-humanTNFR:Fc treated groups were sacrificed on Study Days 45 and 91. Clinical observations were performed daily; food consumption and body weights were assessed weekly; and clinical pathology, organ weights, gross necropsy and hiostopathology were performed at terminal sacrifice. The vector was well tolerated and local transgene expression was confirmed. The highest feasible dose that could be delivered, a dose which was on log higher than the efficacious intra-articular dose of rat vector, did not result in toxicity and resulted in low or undetectable systemic serum levels of human TNFR:Fc protein. Thus, local intra-articular delivery of rAAV-humanTNFR:Fc might result in a reduction of systemic side effects or provide added benefit in joints that are not completely controlled by systemic therapeutics. These data support evaluation of rAAV-humanTNFR:Fc in human patients.
Diagnosis of Brain Tumors: Clinical and Radiographic
Authors: Isabel C. Arrillaga‐Romany, eudocia quant Lee, Patrick Y. Wen
Journal: Neuro-Oncology (2012)

The diagnosis of brain tumors involves careful review of the history and a detailed general and neurologic examination, together with appropriate neuroimaging. In the majority of patients, the differential diagnosis can be narrowed significantly based on the clinical and radiologic features, but histologic confirmation is nonetheless often required.
A Genome Sequence of Novel SARS-CoV Isolates: The Genotype, GD-<i>Ins</i>29, Leads to a Hypothesis of Viral Transmission in South China
Authors: E’de Qin, Xionglei He, Wei Tian, Yong Liu, Wei Li, Jie Wen, Jingqiang Wang, Baochang Fan, Qingfa Wu, Guohui Chang, Wuchun Cao, Zuyuan Xu, Ruifu Yang, Jing Wang, Man Yu, Yan Li, Jing Xu, Bingyin Si, Yongwu Hu, Wenming Peng, Lin Tang, Tao Jiang, Jianping Shi, Jia Ji, Yu Zhang, Jia Ye, Cui’e Wang, Yujun Han, Jun Zhou, Yajun Deng, Xiaoyu Li, Jianfei Hu, Caiping Wang, Chunxia Yan, Qingrun Zhang, Jingyue Bao, Guoqing Li, Weijun Chen, Lin Fang, Changfeng Li, Meng Lei, Dawei Li, Wei Tong, Xiangjun Tian, Jin Wang, Bo Zhang, Haiqing Zhang, Yilin Zhang, Hui Zhao, Xiaowei Zhang, Shuangli Li, Xiaojie Cheng, Xiuqing Zhang, Bin Liu, Changqing Zeng, Songgang Li, Xuehai Tan, Siqi Liu, Wei Dong, Jun Wang, Gane Ka-Shu Wong, Jun Yu, Jian Wang, Qingyu Zhu, Huanming Yang
Journal: Genomics Proteomics & Bioinformatics (2003)

We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.
Reply from Authors re: Charalampos Mamoulakis. A Plea for Higher-quality Data for GreenLight Laser Technology in the Context of Surgical Benign Prostatic Obstruction Trials: The GOLIATH Study—Fact or Fiction in the Era of Evidence-based Urology? Eur Urol 2014;65:943–5
Authors: Alexander Bachmann, J. Andrew Thomas
Journal: European Urology (2013)
PHLEBITIS AND THE DIAGNOSIS OF THROMBOANGIITIS OBLITERANS
Authors: E A EDWARDS
Journal: Annals of Internal Medicine (1949)

Article1 December 1949PHLEBITIS AND THE DIAGNOSIS OF THROMBOANGIITIS OBLITERANSEDWARD A. EDWARDS, M.D.EDWARD A. EDWARDS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-31-6-1019 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptINTRODUCTIONThe making of an early diagnosis in thromboangiitis obliterans is highly desirable. This is true not only because of the serious nature of the malady but also because its progress will usually be arrested if the patient is forced to cease smoking.At least one-fourth of patients with the disease show an early phlebitis of their veins. This has been known since Buerger described it as "migrating phlebitis,"1yet the clinician often misses the opportunity to utilize the presence of venous involvement to make an early diagnosis. This report will try to demonstrate that by careful scrutiny of patients...Bibliography1. BUERGER L: The circulatory disturbances of the extremities, 1924, Saunders, Philadelphia. Google Scholar2. SILBERT S: Etiology of thromboangiitis obliterans, Jr. Am. Med. Assoc., 1945, cxxix, 5-9. CrossrefGoogle Scholar3. KAHN JW: Thrombophlebitis of the deep veins in thromboangiitis obliterans, Surg., Gynec. and Obst., 1946, lxxxiii, 449-452. Google Scholar4. EDWARDSEDWARDS JEEA: The venous valves in thromboangiitis obliterans, Arch. Path., 1943, xxxv, 242-252. Google Scholar5. EDWARDS EA: Migrating thrombophlebitis associated with carcinoma, New Eng. Jr. Med., 1949, ccxl, 1031-1035. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication March 12, 1949.From the Department of Surgery, Tufts College Medical School.Aided by a grant from the Charlton Research Fund, Tufts College Medical School. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThrombo-Angiitis Obliterans (Buerger'S Disease) in the West of ScotlandPhlebitis saltans (migrans)A Critical Evaluation of Thromboangiitis ObliteransKrankheiten der GefäßeSpezieller TeilThrombo‐Angiitis Obliterans�ber cutane Periarteriitis nodosa unter besonderer Ber�cksichtigung begleitender Leberst�rungen und der sogenannten Thrombophlebitis migransRecurring Superficial ThrombophlebitisDeep thrombophlebitis and pulmonary embolism in thromboangiitis obliteransCutaneous Manifestations of Some Common Peripheral Vascular DiseasesThromboangiitis Obliterans in Women 1 December 1949Volume 31, Issue 6Page: 1019-1023KeywordsResearch fundingSurgeryVeins ePublished: 1 December 2008 Issue Published: 1 December 1949 PDF downloadLoading ...
Cytoskeletal regulation of focal adhesion structure: A mechanism to control cell migration.
Authors: Cuc Bach, Jessie Zhong, Lauren Cowell, Peter Gunning, Geraldine O'Neill
Journal: Cancer Research (2007)

3033   Two core components in cell migration are the actin cytoskeleton and integrin-based adhesion to the extra-cellular matrix, known as focal adhesions (FAs). FA turnover allows cells to move over the underlying matrix while the actin cytoskeleton directly links to the FAs providing the contractile force that generates movement. Actin filament structure is regulated by distinct isoforms of the tropomyosin (Tm) family of actin-binding proteins. Given the key relationship between adhesion and actin in cell migration, we hypothesized that Tm isoform expression may regulate adhesion structure, in turn determining downstream signalling and migration. To test our hypothesis we have employed B35 rat cells overexpressing the Tm isoform Tm5NM1 and mouse embryo fibroblasts (MEFs) derived from a Tm5NM1 knockout mouse model. Using time-lapse microscopy we determined that cells expressing Tm5NM1 display reduced random cell movement, while the Tm5NM1 -/- MEFs travel significantly further than controls. Notably, the velocity of the wild-type and knockout MEFs is identical, therefore suggesting that the Tm5NM1 -/- MEFs may be more polarized. Cells overexpressing Tm5NM1 display FAs that are twice the length of control cells and are dispersed across the ventral surface of the cell. In contrast, Tm5NM1 -/- MEFs display enhanced levels of pre-cursor adhesion formation arrayed at the leading edge of protruding membranes. To investigate why the FAs are larger in the Tm5NM1 overexpressing cells we have measured adhesion dynamics. The data demonstrate that the FAs are significantly stabilized in the Tm5NM1-expressing cells. Further the stabilization of FAs in Tm5NM1-expressing cells appears to require the presence of polymerized actin as treatment with the actin-destabilizing agent latrunculin correspondingly promotes FA turnover. We have begun to investigate how altered adhesion structure might impact integrin-mediated signalling pathways and our preliminary data indicate that the FA docking molecule p130Cas exhibits altered phosphorylation in the Tm5NM1 overexpressing cells. In a correlated finding we also observe decreased expression of the tyrosine kinase Src in these cells. Conversely, p130Cas phosphorylation and Src expression levels are unaltered in Tm5NM1-/- MEFs. Collectively, our data support Tm isoform-specific effects on FA structure, adhesion molecule activation and cell migration.
Abstract 13333: Imatinib Attenuates LPS-induced Inflammation and Vascular Leakage in Clinically Relevant Murine Models of Acute Lung Injury
Authors: Alicia N Rizzo, Eleftheria Letsiou, Saad Sammani, Adeline Esquinca, Joe G Garcia, Steven M Dudek
Journal: Circulation (2014)

Introduction: Acute lung injury (ALI) is characterized by inflammation-induced disruption of the endothelial cell (EC) barrier lining the pulmonary vasculature, which causes leakage of fluid and inflammatory cells into the airspaces. The mechanisms underlying ALI are critically dependent on EC cytoskeletal regulation of vascular permeability. The Abl family kinases Abl and Abl Related Gene (Arg) are key mediators of the endothelial cytoskeleton. The pharmaceutical agent imatinib inhibits these kinases and is used clinically for the treatment of multiple different malignancies. Hypothesis: Imatinib attenuates LPS-induced inflammation and vascular leakage in murine ALI and retains its protective properties when combined with high tidal volume (Tv) mechanical ventilation (MV). Methods: As a clinically relevant combination model of ALI stimuli, animals were given intratracheal (i.t) LPS (0.5mg/kg) (vs. PBS), allowed to recover for 20 hours, and then intubated for MV (Tv 30ml/kg, RR 75/min, PEEP 0 cm H2O, 4hrs). Imatinib (75mg/kg) (vs. vehicle) was given i.p. 30 min before LPS and 30 min before MV. For post-injury experiments, imatinib (75mg/kg) (vs. vehicle) was given 4 hours after LPS (1mg/kg) and animals were harvested after 18 hrs. Bronchoalveolar lavage fluid (BAL) was analyzed for total cell counts, neutrophil number, total protein, albumin content, and cytokine levels. Lung tissues were used for MPO activity, albumin content, histology, and Evans Blue dye extravasation. Results: Imatinib attenuated inflammation in both combination model studies and post-LPS treatment studies as measured by BAL cell count, PMN number, MPO activity, TNFα levels, and H&amp;E staining. Additionally, in both models, imatinib decreased vascular leakage as measured by total protein, BAL and lung tissue albumin, and Evans Blue dye extravasation. Conclusions: Imatinib attenuates LPS-induced inflammation and vascular leak in mice. Additionally, imatinib is protective in a clinically relevant murine model of combined LPS and mechanical ventilation injury. Imatinib may have potential for translational use in ALI patients.
Abstract 168: Intermittent Hypoxic/Hyperoxic Cycling Improves Survival of Human Inducible Pluripotent-Derived Cardiomyocytes Subjected to Prolonged Hypoxia
Authors: Mahmood Khan, Ariel Basye, Chun-An Chen, Mark Angelos
Journal: Circulation (2014)

Background: Ischemic and hypoxic pre-conditioning has demonstrated a robust early and late cardioprotection in the heart. Hypoxic pre-conditioning has recently been used with some success to prolong stem cell survival prior to transplantation in the heart. In our previous work, we have noted hyperoxia exposure may also provide a pre-conditioning stimulus. Hypothesis: We hypothesized that brief periods of hypoxic/hyperoxic cycling of human inducible pluripotent derived cardiomyocytes (hiPSC-CMs) prior to prolonged hypoxic exposure will improve cardiomyocyte survival. Methods: Three groups of hiPSC-CMs were studied; 1) HYP group (hypoxia, 0% O2 for 20 hours), 2) HP21 group (two alternate cycles of hypoxia, 0% O2 /normoxia, 21% O2 + 20 hours hypoxia), 3) HP95 group (two alternate cycles of hypoxia, 0% O2/hyperoxia, 95% O2 + 20 hours hypoxia). After the prolonged hypoxic exposure, all three groups were immediately imaged for cell viability using live cell DAPI and phase contrast microscopy. Dihydroethidine (D...
Disodium Cromoglycate and Food Allergy
Authors: Ronald Dahl
Journal: Allergy (1978)

In a food allergic patient challenge evoked a dual asthmatic response. These reactions could be partly or completely blocked by pretreatment with disodium cromoglycate (Intal®, Lomudal®) orally, depending on the doses given. Pretreatment with inhalations of disodium cromoglycate gave no protection.
Lectures on the Diseases of Children: Delivered in the Chatham Street School of Medicine, Manchester
Authors: None Merei
Journal: BMJ (1852)

Treatment of febrile 7heumatism in its various forms.General resnarks regarding the first and principal febrile symptoms.Rhesimatism of the head ntsay be rheumafalgia.or inflammatory rhseusnatism.Issdica- tions regarding the head:-leeches, cold fosszentations, a full dose of calomel, dry covering, mustard pceel/ices, blisters ; effects of, and difficulty with, opiunls
Fortnightly Review: Callosities, corns, and calluses
Authors: D. Singh, G. Bentley, S. G Trevino
Journal: BMJ (1996)

<h3>Summary points</h3> Corns and calluses arise from hyperkeratosis, a normal physiological response to chronic excessive pressure or friction on the skin They may be caused by excessive irritation from poorly fitting shoes or by abnormal pressure if there is a deformity of the foot Treatment should therefore not only provide symptomatic relief (such as by regular paring or using keratolytic agents) but should also alleviate the underlying mechanical cause Most lesions can be managed conservatively by use of sensible footwear (properly fitting shoes with low heels, soft upper, and roomy toebox) and orthoses to redistribute mechanical forces Surgery is rarely indicated and should be specifi- cally aimed at correcting the abnormal mechanical stresses
BACK PAIN AS A SYMPTOM OF CARCINOMA OF THE BODY OF THE PANCREAS
Authors: E E KATTWINKEL
Journal: Annals of Internal Medicine (1945)

Case Reports1 December 1945BACK PAIN AS A SYMPTOM OF CARCINOMA OF THE BODY OF THE PANCREASEGON E. KATTWINKEL, M.D., F.A.C.P.EGON E. KATTWINKEL, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-23-6-1006 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe diagnosis of carcinoma of the body of the pancreas is rarely made correctly during life or preoperatively. If this condition is considered as a cause of back pain associated with indigestion, especially if aggravated by lying down and relieved by bending forward, in the face of negative physical examination, roentgen-ray and laboratory findings, the diagnosis can be made by exclusion and the patient saved the discomfort of unnecessary investigative procedures and expense. Exploratory laparotomy and biopsy are of course essential for a positive diagnosis. The patient is perhaps helped little by such a diagnosis, but the state of uncertainty...Bibliography1. CATTELL RB: Resection of the pancreas, Surg. Clin. N. Am., 1943, xxiii, 753-766. Google Scholar2. BRUNSCHWIG A: The surgical treatment of carcinoma of the body of the pancreas, Trans. 66th Meeting Am. Surg. Assoc., May 1944. Google Scholar3. COMFORTOSTERBERG MWAE: Serum amylase and serum lipase in the diagnosis of disease of the pancreas, Proc. Staff Meet. Mayo Clin., 1940, xv, 427. Google Scholar4. PRATT JA: The diagnosis of pancreatic disease, New York State Jr. Med., 1943, xliii, 1847-1855. Google Scholar5. KIEFER ED: Carcinoma of the pancreas, Arch. Int. Med., 1927 xl, 1-29. CrossrefGoogle Scholar6. KIEFERMORAVEC EDM: The diagnosis of carcinoma of the pancreas, Surg. Clin. N. Am., 1943, xxiii, 738-746. Google Scholar7. BARTELS EC: Carcinoma of the body of the pancreas; back pain a prominent symptom, The Lahey Clinic Bull., 1940, ii, 41-46. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: West Newton, Massachusetts*Received for publication February 19, 1945. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAbdominal PainThe Diagnosis of Cancer of the Pancreas 1 December 1945Volume 23, Issue 6Page: 1006-1009KeywordsBiopsyDeceptionLaparotomyLower back painPancreasResearch laboratories ePublished: 1 December 2008 Issue Published: 1 December 1945 PDF downloadLoading ...
Association between daily levels of air pollution and school absences in the proximity of a cement plant in Italy
Authors: Paolo Girardi, Alessandro Marcon, Giancarlo Pesce, Pierpaolo Marchetti, Salvatore Falcone, Francesca Predicatori, Gianstefano Blengio, Roberto de Marco
Journal: European Respiratory Journal (2012)

Background: Emission of dust represents the main hazard associated with cement production and may cause adverse respiratory health effects to the population living nearby.  Aim: To evaluate the association between daily levels of PM 10  and a morbidity indicator  (school absenteeism) in children aged 7-14 years attending a school within 2km from a cement plant in Fumane (Northern Italy).  Methods: Data on absences of students (average: 461 students/year) and daily concentrations of PM 10  from a fixed monitoring station placed in the schoolyard were collected for 3 school years (541 school days from November 2007 to June 2010). The association between pollution in the same day (Lag 0) and in the previous 4 days (Lag 1 to 4) and school absenteeism was studied using generalized additive Poisson regression models, adjusting for short-term trend, day of the week, flu epidemics and daily temperature.  Results: During the considered period, the daily average concentration of PM 10  was 34.8 µg/m³. An increase of 10 µg/m³ of PM 10  was associated with a significant increase of 2.2% in school absences (RR:1.022; 95%CI: 1.007-1.037) two days after (lag2). The association between average level of pollutants from Lag 0 to Lag 4 and school absences confirmed the presence of a statically significant association with PM 10  levels (RR:1.016; 95%CI:1.003-1.029 for each + µg/m³ of PM 10 ).  Conclusions: Daily PM 10  levels are associated with school absences, a proxy indicator of short-term morbidity, in children who attend schools in proximity to a cement plant. Primary prevention interventions aimed at reducing air pollution in the area are recommended.
Abstract 191: Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer
Authors: Clifford J. Whatcott, Aprill Watanabe, Janine LoBello, Daniel Von Hoff, Haiyong Han
Journal: Cancer Research (2014)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related death in the United States. PDAC is characterized by high levels of fibrosis, a feature termed desmoplasia. Desmoplasia is thought to hamper the efficacy of therapeutics treating PDAC. Agents targeting components of the tumor stroma have shown some enhancement of first-line therapeutics targeting tumor cells. As metastatic burden is one of the primary causes for mortality in PDAC, the question remains of whether stromal targeting therapeutics will benefit patients with late stage, metastatic disease. We sought to address this question by assessing the extent of desmoplasia in both primary PDAC tumors and metastatic lesions of pancreatic origin. Patient tissue staining using a pentachrome or standard immunohistochemical technique demonstrates that extracellular matrix components, such as collagen, are found in high levels in both primary tumors and metastatic lesions. The difference in the level of desmoplasia in primary tumors and metastatic lesions was statistically insignificant. We also observed a significant correlation between patient survival and extracellular matrix deposition. Kaplan-meier curves for collagen I showed median survival of 527 days in low collagen patients, and 176.5 in high level patients. Low level hyaluronan patients displayed median survival times of 2107 days as compared to 385 days in high level patients. Our results indicate that both primary tumors and metastases of PDAC have highly fibrotic stroma. Thus, stromal targeting agents may benefit PDAC patients, even those with metastatic disease. Citation Format: Clifford J. Whatcott, Aprill Watanabe, Janine LoBello, Daniel Von Hoff, Haiyong Han. Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 191. doi:10.1158/1538-7445.AM2014-191