tbuckley/cabot-search huggingface dataset:
AB0005 Investigation of juvenile idiopathic arthritis susceptibility loci: results from a greek population
Authors: D. G. Dimopoulou, G. N. Goulielmos, M. I. Zervou, M. Trachana, E. Myrthianou, P. Pratsidou, A. Garyfallos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid Arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA) [1], an autoimmune disease characterized by chronic arthritis. The strategy of studying the putative role of RA susceptibility genetic factors in the development of JIA has proved highly successfully so far [2]. Moreover, accumulated evidence indicates that an ethnic heterogeneity of genetic factors exists for rheumatic disorders [3]. <h3>Objectives</h3> To investigate whether five single nucleotide polymorphisms (SNPs), found to be associated with JIA in various ethnic populations so far, are also associated with JIA in Greece. <h3>Methods</h3> The sample set consisted of 128 Caucasian JIA patients and 221 healthy controls from Northern Greece. Single Nucleotide Polymorphisms (SNPs) markers that showed association previously with both RA and JIA [4], namely <i>TRAF1/C5</i> rs10818488, <i>PTPN22</i> rs2476601, <i>STAT4</i> rs7574865, <i>CD247</i> rs1773560 and <i>PTPN2</i> rs7234029 SNPs were genotyped with Restriction Fragment Length Polymorphisms (RFLPs) or Taqman primer-probe sets. For the investigation of disease susceptibility, odds ratios (OR) and 95% confidence intervals (CI) were calculated. The statistical difference in genotype and allelic distribution was assessed by two-tailed chi-square test. <h3>Results</h3> A case–control association study was conducted enrolling 5 successfully genotyped markers. The risk alleles <b>T</b> of the <i>PTPN22</i> and <b>A</b> of the <i>TRAF1/C5</i> SNPs analyzed were more common in individuals with JIA than in controls (p=0.043, OR=0.44, 95% CI 0.21-0.97 and p=0.045 OR=1.37, 95% CI 1.01-1.88, respectively). Furthermore, the presence of the risk allele <b>G</b> of the <i>CD247</i> SNP in the genotype appeared to be associated with JIA (p=0.039, OR=1.88, 95% CI 1.06-3-37). <h3>Conclusions</h3> Our findings confirm for the first time in Greece that the <i>PTPN22</i> rs2476601, <i>TRAF1/C5</i> rs10818488 and <i>CD247</i> rs1773560 SNPs are associated with susceptibility to JIA, thus suggesting that the respective risk alleles may confer susceptibility to clinically distinct disorders. Apart from the previously reported evidence for the role of <i>STAT4</i> and <i>PTPN2</i> gene polymorphisms in the development of JIA, our results demonstrate no association of these genes with the disease in a Greek population. The results highlight the importance of comparative studies in different ethnic populations in any attempt to confirm previously detected genetic associations. <h3>References</h3> Ravelli A, Martini A. (2007). Lancet 369:767–778 Hinks A, Eyre S, X Ke X et al (2010). Ann Rheum Dis 69:1049-1053 Gregersen PK, Olsson LM. (2009). Annu Rev Immunol 27: 363–391 Hinks A, Cobb J, Sudman M et al. (2012) Ann Rheum Dis 71:1117-21 <h3>Disclosure of Interest</h3> None Declared
Effects of Prolonged Cortisone Therapy on the Statural Growth, Skeletal Maturation and Metabolic Status of Children
Authors: F. M. Blodgett, L. Burgin, D. Iezzoni, D. Gribetz, N. B. Talbot
Journal: New England Journal of Medicine (1956)

OBSERVATIONS on children suffering from Cushing's syndrome have indicated clearly that adrenocortical steroids of the cortisone type may have a marked tendency to suppress growth.1 , 2 The present study was undertaken, therefore, when it became apparent that the symptomatic relief afforded patients by cortisone might result in the prolonged administration of this hormone to growing children. The chief purpose of the study has been to determine if possible what effect long-continued cortisone therapy might be expected to have on ultimate stature and metabolic status.Material and MethodsThe patients studied were children receiving cortisone because of adrenocortical virilism, panhypopituitarism, hypoadrenocorticism or . . .
Case 29-2001
Authors: Richard M. Terek, G. Petur Nielsen
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 14-year-old boy was admitted to the hospital because of bone pain and skeletal abnormalities.The patient had been vigorously active until one year before admission, when he began to have intermittent pain in his knees, which became more frequent and was followed by the development of pain in the right hip and both feet. Two months before admission, the lower right leg became edematous and tender. Radiographs of the legs, obtained elsewhere, revealed no abnormalities. He was admitted to this hospital.The boy was a native of the Dominican Republic. His diet was adequate and included . . .
Abstract 3673: Identifying the target of an orphan compound: CB30865 is a Nampt inhibitor
Authors: Tracey C. Fleischer, Jeff S. Flick, Ryan T. Terry-Lorenzo, Zhong-Hua Gao, Brett R. Murphy, J Adam Willardson, J Jay Boniface
Journal: Cancer Research (2010)

Abstract Background: Drug discovery based on cellular phenotypes is impeded by the challenge of identifying the molecular target. To alleviate this problem, Myriad Pharmaceuticals has developed a chemical proteomics process to identify cellular proteins that bind to small molecules. CB30865 is a potent and selective cytotoxic compound of previously unknown mechanism of action (1). Using our technology, we have unequivocally demonstrated that CB30865 cytotoxicity is due to inhibition of nicotinamide phosphoribosyltransferase (Nampt). Nampt catalyzes the first step in the synthesis of NAD from nicotinamide. Cancer cells develop dependence on Nampt due to increased energy requirements and the elevated activity of NAD consuming enzymes such as sirtuins and mono and poly(ADP-ribose) polymerases. Materials and Methods: Direct target affinity purification (DTAP) was performed using analogs of CB30865 (MPI-0479883, MPI-0482594) coupled to beads. Purified proteins were identified by nano-flow reversed-phase liquid chromatography and tandem mass spectrometry using an LTQ-Orbitrap. In vitro Nampt activity was measured in a coupled biochemical assay based on the production of fluorescent resorufin. Nampt cellular activity was assayed by measuring levels of NAD and NAD-dependent polyADP-ribosylation. Results: As reported (1), 3-pyridyl, but not 2-pyridyl, analogs of CB30865 were potently cytotoxic. A 55 kD protein was purified efficiently using DTAP with MPI-0479883 (a 3-pyridyl CB30856 analog) but not MPI-0482594 (a 2-pyridyl analog). Preincubation of cellular lysates with uncoupled 3-pyridyl but not 2-pyridyl analogs potently blocked binding of the 55 kD protein. Based on LC-MS/MS analyses, the 55 kD protein was identified as Nampt. Immunoblotting of DTAPs using a Nampt specific antibody confirmed the MS identification. Furthermore, biochemical and cellular assays of Nampt activity demonstrated pyridyl-isomer specific enzyme inhibition. Finally, cellular Nampt inhibition and cytotoxicity were completely rescued by treating cells with 10 µM nicotinic acid as an alternate NAD source. Conclusions: The chemical proteomics DTAP approach is a powerful tool to identify molecular targets of orphan compounds. We demonstrate this here through identification of Nampt as the molecular target of CB30865 and further implicate NAD metabolism as a functional target for cancer. (1) Skelton LA, Ormerod MG, Titley J, Kimbell R, Brunton LA, Jackman AL. A novel class of lipophilic quinazoline-based folic acid analogues: cytotoxic agents with a folate-independent locus. Br J Cancer. 1999 Apr;79(11-12):1692-701. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3673.
NARCOLEPSY
Authors: WILLIAM F. MURPHY
Journal: American Journal of Psychiatry (1941)

1. Narcolepsy is a borderline syndrome common to cases of both functional and organic brain disease. 2. The pathogenesis is the same in both cases and consists of the release of a primitive type of sleep mechanism. 3. Narcoleptic sleep is indistinguishable in appearance and electroencephalographically from normal sleep.
Medicine at the Paris Hospital 1794-1848
Authors: L. S. King
Journal: JAMA (1967)

During the period roughly from 1794 to 1848, the period covered by Dr. Ackerknecht's new book, France led the world in medical progress. The great figures of this era, who made the transition to modern medicine, were leaders in medical thought. Their names are familiar to most of us—Pinel and Bichat, Broussais, Corvisart, Laennec, Louis, Dupuytren. Lesser figures abound, familiar to scholars, although less well-known to the general medical public. The concern with the patient, with physical examination, with careful observation, quite transformed the practice of medicine. The detailed correlation of clinical and pathological findings provided a new and fruitful perspective. New concepts of disease, regarded as process, became quite influential. For this important era there was no systematic book-length study. Consequently, we are greatly indebted to Dr. Ackerknecht for making available a survey of this extremely interesting period, which, in earlier journal articles, he has done so much to
Abstract 179: Histone deacetylase inhibitor; CG005, is a novel anticancer drug; as a combination drug with docetaxel in prostate cancer
Authors: Yong Sook Kim, Mi Joung Kim, Jene Choi, Sejin Jang, Je-hwan Lee, Seonggu Ro, Choung-soo Kim, Jung Jin Hwang
Journal: Cancer Research (2011)

Abstract We synthesized a novel hydroxamate-based HDACi, CG0005 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example SAHA and PXD 101, CG0005 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. The aliphatic chain of CG0005, which is presumed to be positioned at the narrow channel of pocket, is less flexible than that of SAHA and less rigid than that of PXD101. Of the other moieties, the tertiary amine was adopted to improve water solubility. Firstly, we analyzed its activity in hormone-dependent LNCaP cells and hormone-refractory DU145 and PC3 cells. CG0005 inhibited deacetylation of histone3 and tubulin as much as vorinostat and belinostat. CG0005 also inhibited growth of prostate cancer cells and increased sub-G1 population and activated caspase-9, -3 and -8. These results indicated that CG0005 induced apoptosis in prostate cancer cell lines. Next, we examined the effect of CG0005 on cell death induced by docetaxel in DU145 cells in vitro and in vivo. Pre-treatment of DU145 cells with docetaxel followed by CG0005 showed synergistic cytotoxicity, and increased the apoptotic sub-G1 population, caspase activation, and tubulin acetylation, compared with docetaxel alone. Moreover, the combination treatment decreased Mcl-1, Bcl-xl and cyclin D1. Docetaxel and CG0005 combination reduced tumor size in the DU145 xenograft model. These preclinical results show that post-treatment with CG0005 potentiated anti-tumor effect of docetaxel in hormone-refractory prostate cancer (HRPC) cells via intrinsic and extrinsic apoptotic pathway in vitro and in vivo. 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 179. doi:10.1158/1538-7445.AM2011-179
Abstract 4301: Deletion-mapping identifies the regions within MN1 that regulates its transforming activity in hematopoietic cells
Authors: Ayten Kandilci, Jacqueline Bonten, Laura Janke, Geoffrey Neal, Sabrina Terranova, Gerard Grosveld
Journal: Cancer Research (2011)

Abstract The oncogene MN1 is deregulated in human acute myeloid leukemias and its overexpression is known to induce proliferation and repress myeloid differentiation of primitive human and murine hematopoietic cells, which causes myeloid leukemia in mouse models. To study the role of different regions within MN1 in MN1-induced leukemia, we generated in-frame deletion mutants of the protein. Using retroviral transduction assays, we found that the regions between amino acids 12 to 228 and 570 to 1273 are required for its in vivo transforming activity, although the 12-228-mutant was still capable of repressing myeloid differentiation and inducing self-renewal in vitro. Both MN1 and the 12-228-mutant increased the frequency of common myeloid progentiors (CMP) in vitro and microarray comparison of purified CMPs identified Hoxa9, Meis1, Myb, Cebpa, Cebpb and Cebpd among many other differentially expressed transcripts as potential candidates that mediate MN1-induced leukemia. 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 4301. doi:10.1158/1538-7445.AM2011-4301
Economic burden of uncontrolled chemotherapy-induced nausea and vomiting among working-age cancer patients
Authors: Y.-C. T. Shih, S. Han, L. Zhao, L. S. Elting
Journal: Journal of Clinical Oncology (2005)

6053 Background: Poorly controlled CINV may lead to additional office or emergency room visits, thus, increasing the overall costs of cancer care. This study estimates the societal costs of uncontrolled CINV for working-age cancer patients (pts). Methods: Employees or spouse/dependents with (w/) cancer who received highly or moderately emetogenic chemotherapy were identified from a 1997–2002 proprietary dataset linking medical claims to work-loss information. Pts were followed from the earliest date of chemotherapy for up to 6 months, excluding pts w/ < 3 months of continuous enrollment. Three groups, pts w/ uncontrolled CINV and no ER visit, w/ uncontrolled CINV and ER visit, and w/ controlled CINV, were compared in univariate analyses. Uncontrolled CINV was identified by ICD-9 diagnosis codes. Direct medical costs were measured using payments, normalized as monthly, and updated to 2004 $US. Work loss days were identified from employment records. Costs of uncontrolled CINV were derived by comparing costs and days for pts w/ controlled vs. uncontrolled CINV. We used the Wilcoxon Mann-Whitney test to compare costs/days in univariate analyses. All pts w/ uncontrolled CINV were pooled as one group in multivariate analysis. Results: 2,071 pts were identified; 25% required medical care for uncontrolled CINV; 2% had ER visits. (Table) Total direct costs for pts w/ CINV exceeded controlled pts by $2000 - $4000; work loss days were also significantly higher. After controlling for demographics, geographic regions, and comorbidities, the difference in monthly medical costs between the controlled and uncontrolled group was $2,619(P<0.001). However, the difference in work loss was no longer significant. Conclusions: Uncontrolled CINV was associated w/ a significant increase in medical costs. For pts w/ uncontrolled CINV but no ER visit, increases in cost were driven by outpatient care, whereas for those w/ ER visits, inpatient care was the major cost driver. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI
Older Americans Are Priority in Cancer Research
Authors: J. Burklow
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Older Americans Are Priority in Cancer Research Get access John Burklow John Burklow Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 18, 16 September 1992, Pages 1397–1398, https://doi.org/10.1093/jnci/84.18.1397 Published: 16 September 1992
EFFECT OF AGGRESSIVE LIPID THERAPY ON PROGRESSION OF CAROTID ARTERY STENOSIS: A LONGTERM FOLLOW UP STUDY
Authors: Zubair Shah, Rashmi Thapa, Mashood Wani, Suresh Sharma, Taylor Myers, Kamalakar Surineni, Chris Johnson, Lauren Penn, John Fritzlen, Reza Masoomi, Prasad Gunasekaran, G. John Chen, Buddhadeb Dawn, Kamal Gupta
Journal: Journal of the American College of Cardiology (2015)
Abstract 4078: ANT-ligands small molecules induce apoptosis of cancer cells by inhibiting ATP/ADP translocation
Authors: Annie Borgne-Sanchez, Nelly Buron, Mathieu Porceddu, Etienne Jacotot, Catherine Brenner
Journal: Cancer Research (2011)

Abstract Since fifteen years ago, the mitochondrion has been progressively recognized as an integrator-coordinator of apoptosis. In this context recent anti-cancer drugs in development are targeting mitochondrial apoptotic machinery to induce tumor cell death. By this strategy, drugs can interact with apoptosis-regulating proteins of Bcl-2 family to trigger Bax/Bak oligomerization and mitochondrial membrane permeabilization. This event conducts to the release of pro-apoptotic factors such as cytochrome c into the cytosol that are required for caspases activation and apoptosis process. In this study, we selected another strategy and investigated the effect of ANT-targeting small molecules to induce cancer cells apoptosis. The adenine nucleotide translocator (ANT) is a mitochondrial protein of the inner membrane involved in the exchange of ADP and ATP between the mitochondrial matrix and the cytosol. Medicinal chemistry approach coupled with in silico studies yield to several small organic compounds, which proved to be specific for ANT and fulfill druggability criteria (good cell penetration and biodisponibility). We identified a family of compounds that inhibited ATP translocation and induced apoptosis by a pathway involving Bax-dependent cytochrome c release and caspases activation. One of the hit compound was optimized to obtain molecules able to induce apoptosis of HT-29 and BxPC3 cells at 100 nM. We are currently investigating which ANT isoform(s) is (are) targeted in cells. In vivo tumor regression experiments will be performed to achieve the proof of concept of ANT-ligands small molecules as an interesting anti-cancer strategy. 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 4078. doi:10.1158/1538-7445.AM2011-4078
Ornithine Decarboxylase as a Biologic Marker in Familial Colonic Polyposis
Authors: Gordon D. Luk, Stephen B. Baylin
Journal: New England Journal of Medicine (1984)

We investigated whether the activity of ornithine decarboxylase might serve as a diagnostic test for detecting the presence of the genotype for familial polyposis. This rate-limiting enzyme in the polyamine biosynthetic pathway is essential for intestinal mucosal proliferation. In colonic mucosa from 16 normal controls, ornithine decarboxylase activity was less than 2.5 nmol per milligram per hour. In contrast, it was higher than 2.5 nmol per milligram per hour in the normal-appearing areas of colonic mucosa from 11 of 13 patients with familial polyposis and in all polyps biopsied from these same subjects (P<0.05 for specimens from both sites, as compared with controls). Mucosa from dysplastic polyps showed higher mean ornithine decarboxylase activity than mucosa from polyps that were not dysplastic (P<0.05). In colonic mucosa from clinically unaffected, first-degree relatives of patients with familial polyposis, there was a bimodal distribution of ornithine decarboxylase activity, with one peak at the mean for normal controls and the other near the mean for normal-appearing mucosa from affected patients. Our study suggests that ornithine decarboxylase activity in colonie mucosa may reflect the abnormal proliferative state in familial polyposis and identify clinically normal family members who carry the genotype. (N Engl J Med 1984;311:80–3.)
SAT0321 Use of Drug Combinations in Patients with Osteoarthritis: a Population-Based Cohort Study.
Authors: D. Prieto-Alhambra, N. Wilson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with osteoarthritis (OA) use different drugs in search for relief, with potential impact on both safety and costs. There is a scarcity of data on drug utilization in these patients. <h3>Objectives</h3> We used a large database including primary care medical records and pharmacy invoice data to explore use of the following drugs in OA patients in the period 2006-2010: non-steroidal anti-inflammatory drugs (NSAIDs), Symptomatic Slow Acting Drugs for OA (SYSADOA), COX-2 inhibitors (COX2i), opioids, and other analgesics (paracetamol and metamizol). <h3>Methods</h3> SIDIAP contains anonymised clinical information from primary care records and pharmacy invoice data for a representative &gt;5 million people in Catalonia (North-East Spain). We screened this database (www.sidiap.org) to identify those aged 40 years or older with a new diagnosis of OA using ICD-10 codes. Among these, we ascertained prevalence of use of oral NSAIDs, COX2i, SYSADOA, opioids, and analgesics (all alone and in combination) in the period 2006-2011. We estimated prevalence (and 99% Confidence Intervals) of use of these drugs and their combinations, and the proportion of occasional (MPR≥25%) and regular (MPR≥50%) users for each of them. <h3>Results</h3> We identified 281,356 patients with an incident clinical diagnosis of OA. Among these, 128,314(45.6%) were treated with 3 or more drugs, and 57,835(20.6%) with none of the drugs studied. The 3 most common combinations of two drugs were: oral NSAID+analgesic (12.2%); 2.topical NSAID+analgesic (2.5%); and oral NSAID+SYSADOA (1.8%). Besides, 34,672(12.3%) patients received only 1 drug, the 3 most common being, in descending order: oral NSAID, analgesics, and SYSADOA. The proportions of occasional and regular users were highest for SYSADOA (24.5% occasional and 6.9% regular users), and lowest for opioids (7.3% occasional and 1.9% regular users). <h3>Conclusions</h3> About 75% of OA patients are treated with at least 2 drugs, and above half of them with 3 or more. However, compliance with these drugs is very low, and hence both clinical benefits and safety issues are difficult to predict using data from clinical trials, where compliance is high. These data are of interest for health care provision and clinical management of patients with OA. <h3>Disclosure of Interest</h3> D. Prieto-Alhambra Grant/research support from: Unrestricted grant from BIOIBERICA SA, N. Wilson: None Declared