tbuckley/cabot-search huggingface dataset:
887. Bone Formation by Ex Vivo Gene Therapy Using Lentiviral Vector Expressing BMP-2 under the Control of the MLV Promoter
Authors: Osamu Sugiyama, Dong Sung An, Seth Gamradt, Nancy Q. Liu, Irvin S. Y. Chen, Jay R. Lieberman
Journal: Molecular Therapy (2004)

Objective: Bone morphogenetic protein-2 (BMP-2) is an osteoinductive growth factor that can induce bone formation in vivo. Bone marrow stromal cells (BMSCs) are attractive targets for ex vivo gene therapy, and have been reported to differentiate into osteoblasts in the presence of BMP-2. Although we previously demonstrated that ex vivo gene therapy using an adenovirus expressing the BMP-2 induced bone formation successfully in animal models, the transient protein production may not be of adequate duration to heal large bone defects. Lentivirus is known to infect both dividing and non-dividing cells and induce long-term transgene expression. The objective of this study is to examine the potential of ex vivo gene therapy to enhance bone repair using a lentiviral vector.
Topical sunscreens and vitamin D
Authors: R.S. Dawe
Journal: British Journal of Dermatology (2012)

Journal Article Topical sunscreens and vitamin D Get access R.S. Dawe R.S. Dawe Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: rdawe@nhs.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 2, 1 August 2012, Pages 229–230, https://doi.org/10.1111/j.1365-2133.2012.11118.x Published: 01 August 2012
Abstract P160: Ankle-Brachial Index and Fracture Hospitalization in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Shoshana Ballew, Yingying Sang, Andrea L Schneider, Morgan Grams, Laura R Loehr, Hirofumi Tanaka, Gerardo Heiss, Elizabeth Selvin, Josef Coresh, Kunihiro Matsushita
Journal: Circulation (2015)

Background: Several studies indicate that lower extremity peripheral artery disease (PAD), commonly defined by an ankle-brachial index (ABI) &lt;0.9, can increase the risk of bone fracture via its impact on physical function and mobility. Because the majority of prior studies are limited to older white male populations (age ≥65 years), uncertainty remains regarding this association in non-whites, women, and younger individuals. Methods: We studied 15,160 ARIC participants (age 45-64 years in 1987-1989) whose ABI was measured in a randomly selected leg at baseline. Hip or lower extremity fracture-related diagnostic codes were identified through active surveillance of hospitalizations. We used Cox proportional hazards to estimate the independent association between ABI including high ABI (≥1.4), a condition shown in PAD with vascular stiffness, and incident fracture hospitalization, adjusting for potential confounders. Results: There were 668 hip or lower extremity fracture hospitalizations during a median follow-up of 22 years. In the crude model, there was a dose-response relationship between low ABI and fracture risk (Table). However, only ABI 0.9-1.1 remained statistically significant after demographic adjustment compared to normal ABI (1.1-1.4) and inclusion of other covariates rendered this association non-significant. The results were largely consistent among most demographic and clinical subgroups, but we observed increased risk of fracture in low ABI (&lt;0.9) among those with history of cardiovascular disease and high ABI (≥1.4) in men, in the fully adjusted model. Conclusion: An independent association of ABI with increased risk of hip or lower extremity fracture hospitalization was not that evident overall in our biracial population of middle-aged adults. However, ABI may contribute to increased risk of fracture in subgroups, warranting further investigation.
Abstract 20824: Aged Garlic Extract Supplemented with B Vitamins, Folic Acid and L-Arginine Reduce the Progression of Adipose Tissue and Coronary Artery Calcium
Authors: Naser Ahmadi, Irfan Zeb, Panteha Rezaeian, Aryabod Razipour, Ferdinand Flores, Fereshteh Hajsadeghi, Ramin Ebrahimi, Matthew Budoff
Journal: Circulation (2010)

Background: We recently reported that aged garlic extract supplemented with B vitamins, folic acid and L-arginine (AGE+S) is associated with a favorable improvement in oxidative biomarkers, vascula...
Abstract 16380: Effects of Red Wine and Vodka on Collateral-Dependent Perfusion and Cardiovascular Function in Hypercholesterolemic Swine
Authors: Louis M Chu, Antonio D Lassaletta, Michael P Robich, Yuhong Liu, Thomas Burgess, Roger J Laham, Joseph D Sweeney, Tun-li Shen, Frank W Sellke
Journal: Circulation (2011)

Louis M Chu, 2011 Finalist and Presenting Author
A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes
Authors: Philip S. Zeitler, Kathryn Hirst, Laura Pyle, Barbara Linder, Kenneth Copeland, Silva A. Arslanian, Leona Cuttler, David M. Nathan, Sherida Tollefsen, Denise E. Wilfley, Francine R. Kaufman
Journal: New England Journal of Medicine (2012)

Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes.
Abstract 1794: The HSP90 inhibitor, AT13387, combined with erlotinib improves response in EGFR-driven xenograft models of NSCLC
Authors: Tomoko Smyth, Jon Lewis, Keisha Hearn, Neil Thompson, John Lyons, Nicola G. Wallis
Journal: Cancer Research (2014)

Abstract Background: Although Epidermal Growth Factor Receptor (EGFR)-driven non-small cell lung cancer (NSCLC) can be successfully treated with EGFR inhibitors such as erlotinib, relapse is common due to the development of resistance. Methods to improve response and delay resistance are therefore of value. Inhibition of the chaperone, HSP90, leads to the depletion of many client proteins, including EGFR, and has the capacity to simultaneously affect many signalling pathways, offering an alternative strategy for targeting EGFR-driven disease. AT13387 is a potent, second generation HSP90 inhibitor currently being tested in Phase II clinical trials. Here we investigated the effects of combining AT13387 and erlotinib in models of EGFR-driven NSCLC. Results: AT13387 single-agent treatment was effective in EGFR-driven NSCLC xenograft models, significantly inhibiting tumor growth of both HCC827 and NCI-H1650 xenograft tumors when dosed once weekly (see table). As expected, treatment with erlotinib caused significant tumor regression in all HCC827 tumors, but was less effective in the NCI-H1650 model; its PTEN status conferring a reduction in sensitivity. However, combination of AT13387 with erlotinib led to a further enhancement of tumor growth inhibition over either of the monotherapies in both of these models. All HCC827 tumors treated with the combination regressed further (by at least 80%), and regression was also now observed in all NCI-H1650 tumors. These data demonstrate that combination with AT13387 has the potential to increase response, despite the differing initial sensitivities to erlotinib of these models. The combination was well tolerated. Effects of AT13387 and erlotinib on EGFR-driven xenograftsCell lineGenetic BackgroundT/C(Median RTV, treated / control)AT1338755 mg/kg ip 1qwErlotinib12.5 mg/kg po qdCombinationHCC827(Day 32)EGFR Del E746_A75026%17%(47% regression)6%(84% regression)NCI-H1650(Day 31)EGFR Del E746_A750/PTEN del35%36%6%(50% regression) Conclusions: AT13387 was shown to improve response when combined with erlotinib in EGFR-driven xenograft models. These data suggest that there is therapeutic potential in an upfront combination of an HSP90 inhibitor, such as AT13387, with erlotinib and support clinical investigation of such a combination. Citation Format: Tomoko Smyth, Jon Lewis, Keisha Hearn, Neil Thompson, John Lyons, Nicola G. Wallis. The HSP90 inhibitor, AT13387, combined with erlotinib improves response in EGFR-driven xenograft models of NSCLC. [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 1794. doi:10.1158/1538-7445.AM2014-1794
Abstract B24: A phosphoproteomic comparison of oncogenic BRAF and MKK1/2 inhibition in human melanoma
Authors: Scott Stuart, Stephane Houel, Nan Wang, William Old, Natalie Ahn
Journal: Cancer Research (2015)

Abstract The purpose of this study was to use phosphoproteomics to gain insight into the different clinical responses to BRAF inhibition, MKK1/2 inhibition, and combined BRAF/MKK inhibition. Experiments were designed to test whether BRAF inhibition may affect a distinct subset of targets that MKK1/2 inhibition does not and whether BRAF and MKK1/2 inhibitors work additively or synergistically when used in combination. To this end, we employed a SILAC-based method to quantify changes in the phosphoproteome of WM239A melanoma cells treated with a clinically relevant BRAF inhibitor (PLX4032; 10μM) or MEK1/2 inhibitor (AZD6244; 10μM) inhibitor. Phosphopeptides were enriched by titanium dioxide prior to fractionation on an electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) column. In a set of three biological replicate experiments, we quantified changes at 23,986 phosphosites on 4,722 proteins. We identified 1,356 phosphosites that decreased in abundance, and 341 that increased in abundance, in response to treatment with either PLX4032 or AZD6244. The overwhelming majority of phosphosites were responsive to both inhibitors. Of the phosphosites that decreased in abundance, 13 responded only to PLX4032, suggesting that certain targets are regulated by BRAF but not MKK1/2. In contrast, we failed to identify any phosphosites that responded only to AZD6244. To determine whether the therapeutic benefit of combined BRAF and MKK1/2 inhibition may be a result of drug synergy, we treated cells either with a single inhibitor or with a combination of AZD6244 and PLX4032, each at submaximal doses (30 nM). We then compared the magnitude of the responses observed with the combination treatment to those observed for each drug alone. Comparison of observed versus predicted changes at 6,463 phosphosites demonstrated that the primary effect of the two inhibitors is additive. Taken together, we show that the combination of BRAF and MKK1/2 inhibitor leads to predominantly additive interactions, and that the BRAF inhibitor has a potential for regulating phosphorylation events that are not targeted by MKK1/2 inhibitor. Citation Format: Scott Stuart, Stephane Houel, Nan Wang, William Old, Natalie Ahn. A phosphoproteomic comparison of oncogenic BRAF and MKK1/2 inhibition in human melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B24.
Development of Pegylated Forms of Recombinant Rhodosporidium toruloides Phenylalanine Ammonia-Lyase for the Treatment of Classical Phenylketonuria
Authors: Alejandra Gámez, Christineh N. Sarkissian, Lin Wang, Woomi Kim, Mary Straub, Marianne G. Patch, Lin Chen, Steve Striepeke, Paul Fitzpatrick, Jeffrey F. Lemontt, Charles O'Neill, Charles R. Scriver, Raymond C. Stevens
Journal: Molecular Therapy (2005)

Phenylketonuria (PKU) is a metabolic disorder due primarily to mutations in the PAH gene that impair both phenylalanine hydroxylase activity and disposal of l-phenylalanine from the normal diet. Excess phenylalanine is toxic to cognitive development and a low-phenylalanine diet prevents mental retardation, but it is a difficult therapeutic option. Previous studies with recombinant phenylalanine ammonia-lyase, PAL, demonstrated pharmacologic and physiologic proofs of principle for PAL as an alternative therapy for PKU but its immunogenicity was problematic. From a series of formulations of linear and branched polyethylene glycols chemically conjugated to PAL, we have created a parenteral therapeutic agent for PKU treatment. All the pegylated molecules were fully characterized in vitro and the most promising formulations were then tested in vivo in the PKU mouse model. The linear 20-kDa PEG-PAL combination abolished in vivo immunogenicity after repeated challenge while retaining full catabolic activity against phenylalanine, suggesting potential as a novel PKU therapeutic.
Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs
Authors: Seok-Goo Cho, Nayoun Kim, Hyun-Jung Sohn, Suk Kyeong Lee, Sang Taek Oh, Hyun-Joo Lee, Hyun-Il Cho, Hyeon Woo Yim, Seung Eun Jung, Gyeongsin Park, Joo Hyun Oh, Byung-Ock Choi, Sung Won Kim, Soo Whan Kim, Nak Gyun Chung, Jong Wook Lee, Young Seon Hong, Tai-Gyu Kim
Journal: Molecular Therapy (2015)

Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10(7) LMP1/2a CTLs/m(2). Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.
The Use of Sodium Salt of Dehydrocholeic Acid (Decholin) as a Choleretic
Authors: E. G. Wakefield, Harry P. Powelson, Charles S. Mcvicar
Journal: Annals of Internal Medicine (1929)

Article1 December 1929The Use of Sodium Salt of Dehydrocholeic Acid (Decholin) as a CholereticE. G. WAKEFIELD, M.D., HARRY P. POWELSON, M.D., CHARLES S. MCVICAR, M.D.E. G. WAKEFIELD, M.D.Search for more papers by this author, HARRY P. POWELSON, M.D.Search for more papers by this author, CHARLES S. MCVICAR, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-6-572 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNeubauer has been foremost in the investigation of a sodium salt of dehydrocholeic acid that would stimulate the liver to increased formation of bile. Most investigators have shown this drug to be practically without toxic effects and that it markedly increases the flow of bile. Our investigation was undertaken to see if we could obtain results comparable to those reported by Neubauer, Rusznyâk and others.Drugs that would increase flow of bile were sought by ancient medical investigators. The term cholagogue which was used to designate drugs that increase the flow of bile came into use between the time of...Bibliography1 BRUGSCHHORSTERS TH: Cholerese und Choleretica. Klin. Wchnschr., 1923, ii, 1538-1539. CrossrefGoogle Scholar2 DEMARÇAY H: Quoted by Legg. Google Scholar3 LEGG JW: On the bile, jaundice, and bilious diseases. New York, Appleton and Co., 1880, p. 157. Google Scholar4 NEUBAUER E: Dehydrocholsaure, ein wirksames, praktisch ungiftiges Glied der Gallensäuregruppe. Klin. Wchnschr., 1923, ii, 1065-1067. CrossrefGoogle Scholar5 NEUBAUER E: Über die Cholagoge Wirkung der Dehydrocholsäure beim Menschen., Klin. Wchnschr., 1924, iii, 883. CrossrefGoogle Scholar6 RUSZNYAK S: Die Wirkung des Dehydrocholsauren Natriums (Decholin) beim Menschen. Ztschr. f. d. ges. exper. Med., 1927, lvii, 537-553. Google Scholar7 STRECKER A: Untersuchung der Ochsengalle. Ann. d. chimie u. pharm., 1848, lxv, 1-37; lxvii, 1-60. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Submitted for publication June 27, 1929. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA history of the dissolution of retained choledocholithiasisThe factor of occult hepatic and biliary tract disease in some cases of allergy 1 December 1929Volume 3, Issue 6Page: 572-577KeywordsBileDrugsLiverSaltsSodium ePublished: 1 December 2008 Issue Published: 1 December 1929 PDF downloadLoading ...
The contingent negative variation in positive and negative types of schizophrenia
Authors: S Oke, R Saatchi, E Allen, N R Hudson, B W Jervis
Journal: American Journal of Psychiatry (1994)

The authors analyzed the contingent negative variations of 20 medicated patients with schizophrenia diagnosed according to DSM-III-R and 20 age- and sex-matched normal comparison subjects. For the patients with schizophrenia, there were significant correlations between contingent negative variation amplitude and two items on the Scale for the Assessment of Negative Symptoms (affective flattening and avolition-apathy) and the total score on this scale. These findings have implications regarding the underlying pathology of negative and positive symptoms of schizophrenia.
Abstract 2014: Additive Cilostazol to Dual Antiplatelet Therapy Achieves Greater Inhibition of Platelet Aggregation Compared With High Maintenance-Dose Clopidogrel in Patients With Acute Myocardial Infarction
Authors: Young-Hoon Jeong, Bong-Ryong Choi, In-Suk Kim, Choong Hwan Kwak, Jin-Yong Hwang, Seung-Whan Lee, Seong-Wook Park
Journal: Circulation (2008)

Objectives The aim of study was to compare platelet inhibition by additive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) and high maintenance-dose (MD) clopidogrel 150mg/d in patients with acute myocardial infarction (AMI). Methods AMI patients undergoing successful stenting (n =90) were randomly assigned to 1 of 3 MD regimens: Standard group, clopidogrel 75 mg/d; High MD group, clopidogrel 150 mg/d; Triple group, additive cilostazol 100 mg twice daily. Platelet functions were evaluated before discharge and 30 days after discharge. Percent inhibition (PI) and a rate of poor responder to clopidogrel were assessed, based on maximal and late platelet aggregation (Agg max and Agg late ). Results Baseline platelet measures were similar in 3 groups. There was more potent and consistent PI by Triple group in all platelet measures. PI of 5 uM ADP-induced Agg max was 3.5% in Standard group, 22.6% in High MD group, and 44.1% in Triple group (p &lt; 0.001). In addition, PI of 5 uM ADP-induced Agg late was 12.3%, 31.5%, and 65.0% in each group, respectively (p &lt; 0.001). Similar results were demonstrated when 20 uM ADP and 6 ug/ml collagen were used. In terms of poor response to clopidogrel (5 and 20 uM ADP-induced Agg max &gt; 50%), fewer patients in triple group (4.3% and 23.3%) met a criteria than those in standard group (23.3% and 73.3%) and high MD group (16.7% and 60.0%) at 30 days (p = 0.028 and &lt; 0.001, respectively). All parameter between Triple and High MD groups were significantly different. Conclusions Triple antiplatelet therapy achieves greater platelet inhibition and lesser rate of poor response to clopidogrel compared with high MD clopidogrel in AMI patients.
Hypothalamic control of the anterior pituitary; an experimental—morphological study.
Authors: János Szentágothai
Journal: JAMA (1963)

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The photosensitive patient: could it be pellagra?
Authors: C.T. Burnett, H.W. Lim
Journal: British Journal of Dermatology (2011)

Funding sources None. Conflicts of interest None declared. Generations of medical students have memorized the four ‘Ds’ of pellagra: dermatitis, diarrhoea, dementia and, less likely, death. Therefore, if a patient presents with the classic triad of a photoexposed dermatitis, diarrhoea and dementia, a diagnosis of pellagra can be readily made. Consider the more likely scenario for a dermatologist in which the patient lacks diarrhoea and dementia, instead presenting solely with photosensitivity and hyperpigmented lichenified plaques on photoexposed skin. Chronic actinic dermatitis (CAD), photoallergic contact dermatitis or phototoxicity might be considered in the differential diagnosis (Table 1). Yet, in a busy dermatology clinic, pellagra could be easily overlooked due to its rarity in developed nations. Pellagra is readily diagnosed with a serum niacin level, and easily treated with oral niacin supplementation. The difficulty lies in identifying those patients at risk of this rare disease. ... This month’s issue of the BJD includes an extensive review of pellagra contributed by Wan and colleagues1 Their thorough discussion provides the clinician with the salient features needed to arrive at a diagnosis. As is the case for other photosensitive disorders, historical clues are important in pellagra. As alcoholics are most likely to be affected in developed nations, serum niacin levels should be evaluated in a photosensitive patient who reports excessive alcohol intake.2 Pellagra may be secondary to anorexia, so the serum niacin should be assessed in a patient with concomitant presence of photosensitivity and history and signs of an eating disorder.3 Cutaneous signs of anorexia are multiple, but may include excessive lanugo hair, xerosis, telogen effluvium or knuckle calluses (Russell’s sign).4 Underlying gastrointestinal disorders such as coeliac disease or inflammatory bowel disease may predispose to pellagra due to malabsorption.5, 6 A photosensitive patient on predisposing medications, which include 5‐fluorouracil, isoniazid and azathioprine, must also be evaluated for the disease.7, 8